UC-NRLF llllill B M 43D DMl <9 <^^- aoscience & NaAl Resourcasl^ibrary ( rti) "-■■ ^o %. %. % ^^ \ ® *"" V/' t f 4 t p >>4 t PHARMACEUTIC CHEMISTRY STANISLAUS A SHORT PHARMACEUTIC CHEMISTRY INORGANIC AND ORGANIC I. V. STANLEY STANISLAUS, M. S., PHAR. D. w Projessor of Pharmacy and Organic Chemistry and Dean oj the School of Pharmacy of the Medico- Chirurgical College of Philadelphia CHARLES H. KIMBERLY, B.S., (in Pharmacy) PH. D., Professor oj Applied Chemistry in the School of Pharmaceutic Chemistry of the Medico- Chirurgical College of Philadelphia SECOND EDITION PHILADELPHIA P. BLAKISTON'S SON & COMPANY 1012 WALNUT STREET 1908 ^f*f/i^i Copyright, 1908, by I. V. St.\nley Stanislaus. ''Authority to use for comment the Pharmacopceia of the United States of America Eighth Decennial Revision, in this volume, has been granted by the Board of Trustees of the United States Pharmacopoeial Convention, which Board of Trustees is in no way responsible for the accuracy of any translations of the official weights and measures or for any statements as to strength of official preparations." Printed by The Ma fie Press York, Pa ERRATA. 69. -Line 11: 69. —Line 12: 69.- —Line 25: 73-- —Line 3: 74-- — Line 7 : 74- —Line 22: at 25° 75-- —Line 2: 87.- —Line 14: -Under OXYGEN read — "A gaseous element. Symbol O. Atomic Weight 16. Valence 2." " 1.52 " should be " 1.403". "86° C." should be " 120.5° C" Omit "H— HCN". " 1.83 " should' be " 1.826." "AsOj" should be "AszO,". "1.71 at 15° C." should be "1.707 "At 15° C." should be "at 25° C." "Argenti nitras dilutus" should be " argenti nitras mitigatus." 113. — Line 10: "Ferri sulfas" should be 'ferri sulphas." 113. — Line 18: "Ferri sulfas exsiccatus " should be 'ferri sulphas exsiccatus." 113. — Line 22: "Ferri sulfas granulatus" should be "ferri sulphas granulatus." "37.8%" should be "29%". "62.9%" should be "42.8%". "60%" should be "55%". " 198.3 " should be " 198.5 ". " 198.3 " should be " 198.5 ". "40° to 70° C." should be "45° 80° C." should be "57.2°C." 34.6° C." should be "35.5° C." 500 parts" should be "360 parts." 115° C." should be " 113° C." 170° to 185° C." should be "155° 114. — Line 21 114. —Line 22: 137- —Line 26: 178. -Line 8: 178. —Line 14: 223. —Line 13: to 60° C 223. —Line 20 317-- —Line 8 343- —Line 13 437-- —Line 3 547-- —Line 18 to 165 °C .otfiSEl^ >^. TO THE MEMORY OF THE VENERABLE ALBERT ETHELBERT EBERT, Ph. M., Ph. D-., THE NESTOR AND CHAMPION OF AMERICAN PHARMACY THIS MODEST VOLUME IS RESPECTFULLY DEDICATED BY THE AUTHORS. 192868 PREFACE TO THE SECOND EDITION. Eleven years have elapsed since the printing of the first edition, and so much progress has been made in the science of chemistry in the last decade that the manual had to be entirely rewritten. In revising the work, the author sought the aid of Professor Charles H. Kimberly, who has brought up to date the Inor- ganic part. This book has been written for students of Phar- macy and prepared mainly from the hectographed lecture and laboratory notes which have been periodi- cally distributed to our students. When only a limited period of time is devoted to the study of chemistry, as is customary in pharmaceu- tic schools, it is, in the opinion of the authors, un- wise to burden the student's mind with details of little bearing on Pharmacy. With this in view, they have based the text upon the United States Pharmacopoeia. In no way, however, is the book designed to usurp the place of the national standard, to which it is intended as an introduction. In the first chapters the elementary principles, such as definitions, nomenclature, notation, etc., are ex- plained, followed by a discussion of the nonmetals. The next few chapters are devoted to the metals and their inorganic compounds, equation writing, stoichi- ometry, "periodic classification," etc. vii Viii PREFACE TO THE SECOND EDITION. The second ])art of the l)ook is devoted to Organic Chemistry in which the classification and sequence are based on the excellent lectures of Professor Daniel C. Mangan. In this portion, the needs of pharma- ceutic students have been kept constantly in view and all of the important "newer remedies" discussed with regard to their derivation and synthesis. Class reactions, syntheses and properties of entire classes are given wherever possible. The articles on ele- mentary analysis, deduction of molecular formulas and toxicology, while brief, are complete. The final e is dropped from the names of the halo- gens and binary compounds and organic compounds, but retained in the case of the alkaloids, and an ar- bitrary classification of the inorganic compounds into analytic groups has been attempted. It is hoped that the book will take the place of the often incomplete and inaccurate lecture-room notes. The thanks of the authors are due to Mr. Joseph L. Turner, who read the proofs of the organic part, to Miss Mary White Hutchinson, who has rendered valuable assistance in the preparation of the manu- script, and they wish to especially express their thanks to Professor George H. Meeker for his words of en- couragement and for kindly ])lacing at their dis])osal his valual>le notes. I. V. s. s. C. H. K. Philadelphia, November, 1908. TABLE OF CONTENTS. PART I. Page Inorganic Chemistry Discussion, i Classification of Compounds, 15 The Nonmetals, 18 Water, Discussion of, 48 The Atmosphere, 61 The Inorganic Acids, 67 The Metals and their Compounds, 7^ Ionic Theory, Physical and Electro-Chemistry, 178 Chemical Nomenclature, Formulas and Definitions, . . 182 Equation-writing, 187 Stoichiometr}-, 196 PART 11. Organic Chemistry, Discussion of, 201 Compounds of Carbon, 215 Purification of Organic Compounds, 558 Separation of Organic Substances with Immiscible Solvents,, 559 Qualitative Tests for Elements in Organic Compounds, . 561 Elementary Organic Analysis and Deduction of Formulas, 5^3 Volumetric Analysis, Elementary Discussion, 566 Determination of Molecular Weight, 57 ^ Toxicology, Elementary Discussion, 577 Index, 59^ ix OF THE UNIVERSITY OF PHARMACEUTIC CHEMISTRY PART I. INORGANIC CHEMISTRY. CHAPTER I. MATTER. The science of chemistry has been advanced so rapidly in recent years that it is almost impossible to keep pace with its progress. For this reason it has been divided into branches, each of which em- braces or covers a special line of human endeavor. Thus, we have "Agricultural Chemistry," which deals with the problems of successful farming; "Metallurgical Chemistry," which deals especially with metals, their analysis and application in the arts. Why, therefore, should we not have "Phar- maceutic Chemistry," dealing with the chemistry of medc'nes. It is justly held by some that "Chemistry is no less the same science, whether applied to metallurgy, medicine or pharmacy." But that after mastering the underlying principles, a certain branch of it should be specialized in, no one will deny. 2 I'lTARMACEUTIC CHEMISTRY. GENERAL CONSIDERATIONS AND DEFINITIONS. MATTER is that substance of which all bodies are composed. Thus, earth, wood, air, water, iron, gold, etc., are matter, though differing from one another in their properties. Matter exists in three states oj aggregation: (i) solids; (2) liquids; (3) gases. Matter is impenetrable and indestructible. Ac- cording to subdivision (size), it is divided into ^^ masses,'" ^^ molecules'" and "atoms." Any distinct portion of matter appreciable to the senses is called a mass. The smallest portion of matter which can exist by itself and retain its peculiar characteristics is called a molecule (little mass). The smallest particle of matter into which mole- cules can be divided is called an atom (not cut). Atoms are hypothetical bodies, supposedly indi- visible solids, with a definite, unchangeable weight and possessing a definite amount of attraction .for other atoms which they neutralize and with which they unite. An atom cannot exist by itself, but it unites with other atoms of the same kind to form molecules. Molecules, likewise, unite with other molecules to form masses. When molecules of similar c()m])t)siti()n are at- tracted to each olluT, flie force causing such attraction is termed roliesioii; when, liowever, (he CONTINUITY OF MATTER. 3 molecules are of unlike composition the force is called adhesion. Atoms attract each other by a force known as chemism or cliemical affinity. CONTINUITY OF MATTER.— ^^■hen a bar of iron is heated it expands; when cooled it contracts. The following reason for this change is given: It is assumed that the metal is composed of minute par- ticles of matter which are not in absolute contact and which recede from each other upon the application of heat or approach each other when heat is with- drawn. That matter is not continuous can further be proven by the fact that when liquids of different densities are mixed (as, for example, alcohol and water) the bulk of the mixture contracts (shrinks). Thus, if 100 cubic centimeters of alcohol were mixed with 100 cubic centimeters of water, instead of hav- ing 200 cubic centimeters, as one would suppose, the mixture measures but 194 cubic centimeters. The loss in volume (bulk) of 6 cubic centimeters, or 3 per cent., shows clearly that between the particles of one of the liquids there must be open spaces which particles of the other liquid enter and thus cause the shrinkage. There are many other proofs that matter is not continuous, but the above two familiar examples will, it is thought, suffice to show that matter is com- posed of exceedingly small particles which are not rigidly joined together, but which exist at some mi- nute distances apart from one another; and, further, that these particles are in a state of constant motion 4 PHARMACEUTIC CHEMISTRY. (vibration) which is increased by raising, and de- creased by lowering the temperature of the substance. The minute particles referred to are called molecules, which we have already defined. Since all compounds are made up of two or more substances into which they may be split, it follows that molecules must consist of smaller particles. Thus, if a molecule of hydrochloric acid be separ- ated into its elements, we obtain a particle each of hydrogen and of chlorin — these smaller particles being the atoms referred to above. Molecules of compounds may consist of any num- ber of atoms; molecules of elements consist usually of only two atoms. ELEMENTARY AND COMPOUND MATTER.— Matter may be either (i) simple or (2) compound. When consisting of only one kind of elementary substance, as iron, copper, carbon, oxygen, etc., it is simple matter. Compound matter consists of two or more kinds of matter in combination, as water, which consists of hydrogen and oxygen; or iron sulfate, which con- sists of iron, sulfur and oxygen, etc., and which are, therefore, compounds. Simple matter — because it cannot be reduced with the means at our disi)osal to anything simpler — is called elementary matter or an element. .An clement, therefore, it is assumed, consists of but one kind of matter. About eighty kinds of clemenlar\ mailer or ele- ments are known, and it is reasonable to suppose PHYSICAL SCIENCE. 5 that others remain to be discovered. Of these elementary substances combined in different pro- portion every kind of matter is composed. Indeed, the entire universe is constructed of elementary matter. Many of the compounds discovered in nature have been reproduced or duplicated in the chemist's laboratory and the list of compounds is constantly increasing. SOLIDS, LIQUIDS AND GASES.— It has been stated above that matter exists in three forms. Any one of these three forms of matter can be converted into either of the other two. For example, ice is a solid, but when melted it becomes liquid (water). By boiling the liquid water, a gaseous vapor or steam is produced. All matter is influenced by two phy- sical forces, the force of attraction (cohesion) and the force of repulsion, and according to the pre- dominance of either of the forces, the different forms of matter result. Thus, when the force of attraction is greater, solids result; when the force of repulsion equals the force of attraction, we have liquids; when, however, the force of repulsion is greater than that of attraction, gases result. PHYSICAL SCIENCE.— We cannot create or destroy matter, we can only alter its form and arrange differently the particles of which it is composed. We can, however, by study understand the changes which are taking place in nature. The study of these changes in all their many forms is called ^^ Physical Science." PHYSICS is a branch of physical science which 6 PHARMACEUTIC CHEMISTRY. treats of the phenomena of matter as such, without regard to its composition. CHEMISTRY is the science which treats of the composition of bodies and the changes which this composition may undergo. Since chemistry reveals to us the secrets of the hidden particles, the term is thought to have its derivation in the Arabic word meaning "to conceal" (kamai). Physics and chemistry are very closely allied, since nearly all chemical changes are accompanied by physical changes, and many physical changes in- volve chemical changes as well. PHYSICAL AND CHEMICAL CHANGES.— A physical change is one in which the composition and properties of a substance are not permanently altered. A chemical change is one in which both the composi- tion and properties of a substance are permanently altered and one or more new substances produced. To illustrate these changes, we can take ordinary salt — sodium chlorid : It is a solid, but when placed in water it dissolves, losing its solid form. If we evaporate the water we obtain the salt in its original form, hence no permanent change took place. Such a change is called a physical change. If, however, we place the salt in sulfuric acid, while it again dis- solves, on evaporation an entirely different compound results. A permanent change has taken place and a new compound j^ossessing different properties has been formed. Such a change is known as a chemi- cal change. Chemical changes, also called reactions, when CHEMISTRY DEFINED. 7 expressed by means of symbols and signs are called equations. Chemistry is divided into (i) Inorganic and (2) Organic. INORGANIC CHEMISTRY treats of the metals and nonmetals, or materials coming from unorgan- ized (mineral) sources. ORGANIC CHEMISTRY is the study of carbon and its compounds. The older definition of organic chemistry, and the reason for its adoption as a sepa- rate classification, was due to the suppos'tion that the class of compounds called "organic" originated in living tissue, hence of plant or animal origin. We know now that many such compounds can be made artificially from carbon and the inorganic elements. The term "organic chemistry," however, survived. CHAJ>TKR II. GENERAL DISCUSSION. In order to conveniently study the elements which are of importance to the student chemist, it is nec- essary to classify them. Many systems of classifi- cation have been proposed, many purely arbitrary, but all open to criticism. Berzelius was the first to divide the elements into two large classes which he called "metals" and "metalloids." The metals he considered to be those which possess luster and opacity, easily conduct heat and electricilv, and are electro-positive in their combinations. The metalloids — also called nonmelals — consist of gases, or if solids, possess no luster, ductility or mal- leability, are poor conductors of heat ^nd electricity and are electro-negative in their combinations. We know that this classification serves only in a general way, for a number of the elements are posi- tive in one combination and negative in another; some metalloids possess a luster; some form alloys with metals; some form both acids and bases and, owing to these properties, may {)roperly be placed in both divisions. The most reasonable method of classification is by dividing the elements into groups, which is the system first i)roposed by Ncwlands, but later developed bv MendelejefT. This is the method most commonl\ 8 coMPOUNns. 9 used. It is based upon the atomic weights and is known as the ''Periodic Lwic." The system will \)C fully described in Chapter XVI. This classification, also, has irregularities, but it seems to be the best at hand and has stood the test of years. Our method of grouping is very arbitrary. We, of course, retain the two divisions of — metals and nonmetals — but take up the study of non- metals first, since it is by far the smaller group. The metals, however, we have grouped according to their behavior with reagents, which is considered' most advantageous for the i)ractica] work of the pharmaceutic chemist. COMPOUNDS AND MECHANICAL MIXTURES.— These are dift'erentiated as follows: In a mechanical mixture there is no true union of the elements; in a compound there is. A mixture possesses all the properties of its ingredients, and these ingredients can be mixed in any arbitrary proportions. A chemical compound, on the other hand, possesses entirely different properties than the elements composing it, and its components are defi- nite, fixed and invariable. Example: if iron is re- duced in a mortar to the finest possible powder, and if ordinary sulfur, also in fine powder, is mixed with it intimately, the mixture will present a uniform appearance. If, however, a small quantity of it is placed under a microscope the particles of iron and sulfur will be found lying side by side. If we now use a magnet we can pick out the iron filings and leave the sulfur behind, or we can treat the lO PHARMACEUTIC CHEMISTRY. mixture with carbon disulfid which dissolves the sulfur and leave the iron behind. But, if a portion of the mixture is heated to redness, a chemical change occurs and a true compound is formed, in which neither the sulfur nor the iron can be revealed under the most powerful microscope. The product pos- sesses properties unlike either of its composing ele- ments and a magnet is now incapable of abstracting iron from it, and carbon disulfid will not dissolve out the sulfur. This is, therefore, an illustration of the fact that before heating it was simply a me- chanical mixture, while after heating we had a true chemical compound (ferrous sulfid, FeS). Another proof that this is a chemical compound is that when it is treated with dilute sulfuric acid a gas possessing the odor of bad eggs is evolved. Neither the iron nor -sulfur treated with sulfuric acid before they are combined will evolve this gas. ELEMENTS AND COMPOUNDS.— As was said above, elements are bodies that have resisted all attempts to decompose them into simpler forms of matter. Thus, silver, gold, copper, are solid ele- ments; bromin and mercury are liquid elements; hydrogen, oxygen, nitrogen, chlorin and fluorin are gaseous elements. Elements, therefore, exist in all three forms of aggregation. A compound was defined as a body composed of two or more elements and is, therefore, capable of being split up into its components. Thus, mer- curic oxid, HgO, is composed of mercury and oxy- gen, and hv siinpl\- heating il. it is possible to resolve ATOMIC WEIGHT. 11 it into mercury and oxygen, the first being a liquid metal, the latter a gas. The elements are divided into two series: the nonmetals and the metals. There are sixteen non- metallic elements, the balance are all metals. All metals are capable of being polished. They possess a peculiar surface referred to as "metallic luster." They are all white to light blue or gray, with the ex- ception of gold which is yellow and copper which is of a red color. The nonmetals, on the other hand, are destitute of the metallic luster, and such elements as phosphorus, sulfur and carbon are examples of the nonmetals. SYMBOLS. — A symbol may be said to be a short- hand method of representing an element. For con- venience in writing chemical reactions and for many other reasons these symbols are employed. They are usually the initial letters of the Latin name of the elements. Thus, H stands for hydrogen ; O for oxy- gen; N denotes nitrogen; S sulfur; P phosphorus, etc. When more than one element have names beginning with the same initial letter, another charac- teristic letter is added. The first letter is always a capital, the second usually small. Thus, Hg for hydrargyrum; Os for osmium; Ni for nickel; Sb for stibium; Pb for plumbum. ATOMIC AND MOLECULAR WEIGHTS.— The elements possess definite weights of their own. The atomic weights of the elements represent (a) the relative weights of the atoms compared with hy- drogen; (b) the smallest quantity by weight which can 12 PTTARMACEL'TIC CHEMTSTRY. enter a chemital comijound, this also compared with hydrogen; (c) the specific gravity of the element in the gaseous state as compared with hydrogen. The atomic weight of any element, therefore, is the number of times its atom is heavier than an atom of hydrogen. Hydrogen, being the lightest sub- stance known, is generally used as the standard of weight for the elements. Its atomic weight is taken as unity; that is, it weighs one microcrith. When, therefore, we speak of oxygen having the atomic weight of 1 6, we understand it to weigh sixteen times as much as the hydrogen atom, or that it weighs i6 microcriths. In the same way we determine that the atomic weight of carl)on is 12; nitrogen, 14; sodium, 23; potassium, 39; calcium, 40, etc. Molecular weight of a compound is the sum total of the atomic weights in a molecule of the substance. Thus, CaO represents a molecule of calcium oxid, or common lime; from its formula we see it is com- posed of one atom each of calcium and oxygen. Now, the atomic weight of calcium is 40 and that of oxygen is 16. If we now add 40 and 16 we obtain the sum total of the atomic weights in the molecule, or 56; 56, therefore, is the molecular weight of cal- cium oxid. Common chalk, as another example, has the formula CaCOj. We find here a molecule composed of one atom of calcium which weighs 40; one atom of carbon, atomic weight 12; and three atoms of o.xygen, atomic weight 16 — taken three times, or 48. If we now add (40 -f- 12 -f 48 = 100), the atomic weights of each of the elements in the VALENCE. 13 molecule, we obtain the sum of 100, which is the molecular weight of calcium carbonate, or chalk. QUANTIVALENCE, ATOMICITY, VALENCE OR "BONDS." — By the valence of an element its atom- fixing power is meant. It may be defined as " the combining power of the atoms of an element as com- pared with that of hydrogen." It will be seen here that hydrogen is a unit of valence as well as a unit of weight. Atoms of certain elements have a combin- ing power equal to the atoms of hydrogen. Thus, one atom of chlorin unites with one atom of hydro- gen. Hydrogen, being the unit, has a valence of i, and is called a monad or a univalent element. It therefore has i combining or replaceable "bond." Oxygen has a valence of 2, it is spoken of as a dyad and has 2 combining or replaceable bonds. Nitro- gen is a triad, having 3 replaceable bonds; carbon, a tetrad, having 4 bonds, and phosphorus, a pentad, having 5 bonds. It will be seen that to neutralize the two bonds of oxygen two hydrogen atoms will be required, thus: — O — shows the two bonds of ox3'gen, and H — O — H shows these two bonds united to two monad hydrogen atoms, forming a "saturated" or "perfectly balanced" compound. Nitrogen, having three bonds, must be united with 3 hydrogen atoms in order to form a saturated /H compound. Thus, N- -H shows the nitrogen \,H atom to be saturated, giving rise to a compound having the fcjrmula NH3, and commonly called am- 14 PHARMACEUTIC CHEMISTRY. monia gas, etc. Thus, it will be seen that elements can be divided according to their bonds or combining values into monads, dyads, triads, tetrads, pentads, hexads and heptads accordingly as they can replace I, 2, 3, 4, 5, 6 or 7 hydrogen atoms or its equivalent in the molecule. VARIABLE VALENCE.— While an element has always the same valence in the same compound, it may exhibit a different valence in different com- pounds. Thus, nitrogen, as has been seen in the case of ammonia, exhibited the valence of 3. In nitric acid, however, and in all the nitrates it is always 5. Many other elements have this variable valence. Thus: Sulfur, Chromium, Manganese act as dyads, tetrads and hexads. Arsenic, Antimony, Phosphorus act as triads and pentads. Carbon acts as dyad and tetrad. Iron acts as dyad and triad. Tin acts as dyad and tetrad. CHEMICAL FORMULAS.— A formula is an ex- pression of the composition of a molecule. It con- sists usually of two or more symbols written together, and represents a definite molecular weight. If water, represented by the formula HjO, is taken for example, it is seen to be composed of two parts by weight of hydrogen and 16 jiarts by weight of oxygen; the molecular weight of water, therefore, is 18. KCl is the formula for potassium chlorid and rejiresents 74.4 jxirts of ])otassium chlorid, which is the sum total of 39, the atomic weight of potassium, and ,:;5.4. COMPOUNDS CLASSIFIED. I 5 the atomic weight of chlorin. When we desire tt) represent more than one atom of an element it is nec- essary to affix a small numeral at the lower right-hand corner of the symbol representing the element. Thus Na2 represents two atoms of sodium, or 46 parts of sodium by weight. In the same way O3 represents 3 times the atomic weight (16), or 48 parts of oxygen by weight. Common soda has the formula Na2C03; if we wish to represent more than i molecule of common soda, we place a large numeral before the formula. Thus, 3Na2C03 represents 3 molecules of soda, the 3 multiplying each of the atoms in the molecule. 4HCI represents 4 molecules of hydrochloric acid and stands for 4 hydrogen and 4 chlorin atoms. 2H2SO4, on the other hand, is the formula of two molecules of sulfuric acid and it stands for 4 atoms of hydrogen, 2 atoms of sulfur and 8 of oxygen. Thus the nu- meral placed before the molecule multiplies all the atoms in the molecule, while a numeral placed after a symbol multiplies only that one symbol. If a group of symbols (NH^) is followed by a nu- meral, the whole group is multiplied by that numeral. Thus, (NHJ3 stands for 3 molecules of ammonium; (NO)^ stands for 4 molecules of nitric oxid, etc. CLASSIFICATION OF COMPOUND^.-- Com- pounds are classified into leases, acids and salts. Bases are the hydroxids of the metals. Some bases are soluble, others not. The soluble bases have a caustic taste and turn red litmus paper ])luc. Slaked lime is a common example of the bases. l6 PHAKMACKUTIC ( HEMISTRY. Acids are defined as the salts of hydrogen. They have a sour taste, are corrosive and turn blue litmus red. Salts are acids in which part or all the basic hydro- gen has been replaced by a metal. Salts are named after the element and the acid from which formed. Thus, if potassium replaces the hydrogen of sulfuric acid — potassium sulfate is formed. The salts are usually classified or subdivided into normal, acfd, basic and double salts. A normal salt is an acid in which all the basic or replaceable hydrogen has been replaced by a metal, as in potassium tartrate (KsC^H^Og). An acid salt is one in which not all of the basic hydrogen of the acid has been replaced, as in ])otas- sium bitartrate (KHC^H^OJ. A basic salt is an acid in which part of the hydrogen has been replaced by a metal and another part by an oxid or a hydroxid. Thus, basic lead acetate (lead sjI acetate) serves a good example: Pb(PbO) (C,H30,).,. Adouble salt is an acid in which the basic hydrogen is replaced by two metals. Example: Potassium, sodium tartrate (Rochelle salt)— KNaC^H^Og. CLASSES OF ACIDS.— The acids are divided into those con'taiiiing no t)xygen^ which are termed liy- dracids, and those containing t)xygen which are termed oxacids. Tlie names of all hydnuids i)egin with llie jjrefix hydro and the names of their ."^alts end witli the suflix id (ide). K.xamples: .Acid hydro- chloric, acid hvdriodic, acid hvdrobromic. acid nonmf:tals classified. 17 hydrosulfuric. Such well-known acids as sulfuric, nitric and oxalic belong to the class of oxacids. In the oxacids the quantity of oxygen present in the acid determines their names. Thus, names of acids containing lea.t oxygen begin with hypo and end in ous. Those containing the next larger quantity of oxygen end in ous omitting the hypo. The next higher acid ends in ic, while the high- est acid begins with per and ends in ic. The fol- lowing chlorin oxacids serve as examples: Hy- pochlorous acid (HCIO), chlorous acid (HClOj), chloric acid (HCOj), perchloric acid (HCIO,). CLASSIFICATION OF THE NONMETALS. The nonmetals, grouped according to their valences, are as follows: Hydrogen Group: Hyflrogcn H Chlorin Group : Chlorin CI Bromin Br lodin I Fluorin . F Sulfur Group : Oxygen O Sulfur ] S Selenium | Se Tellurium Te Nitrogen Group : Nitrogen ' N Boron B Phosphorus I P Carbon Group : Carbon (" Silicon Si CHAPTER III. THE NONMETALS. HYDROGEN. A GASEOUS element. Symbol, H. Atomic weight, I. Molecular weight, 2. Valence, i. Density, i. Weight of one liter = 0.0899 gm. (0.09). One gram of hydrogen at 0° C. and 760 millimeters pressure will occupy 1 1. 1 6 liters of space. Occurrence. — Hydrogen was discovered by Caven- dish (1766). It occurs in the free state in gases from volcanoes, several semi-active fumaroles and in the atmosphere of the sun. In combination it is a con- stituent of water and in most organic substances of both animal or vegetable origin. It is a necessary constituent of all acids, bases and ammoniacal com- pounds. Does not exist free on the earth, but has been found free in meteorites which have fallen upon the earth. Preparation. — Hydrogen is produced by the fol- lowing methods: (i) Electrolytic decomposition of water; hydrogen collecting upon the negative pole. H.,0 -f electrolysis = H, + O. (2) By the action of metallic sodium or potassium on water. 2H,0 + Na, = 2NaOH + H^. 18 HYDROGEN. Jg (3) Action of steam on red-hot iron. 4H2O + 3Fe = FegO^ + H^. (4) Chemical reactions. Decomposition of mineral acids by a metal, usually zinc or iron, and dilute sulfuric acid. H2SO, + Zn = ZnSO, + H,. This latter method is usually employed in labora- tories. Dilute sulfuric acid is used to prevent the crystallization of the zinc sulfate produced. If ab- solutely pure zinc is used, no action will take place unless an electric current is passed through the solu- tion. Since commercial zinc is usually employed, the hydrogen obtained is not entirely pure, but con- tains some other gases derived from the impurities of the zinc. Properties. — When pure and at normal temperature and pressure, hydrogen is a colorless, transparent, odorless and tasteless gas. It is invisible, combus- tible, but does not support combustion. Burns with a pale-blue flame, forming water. Hydrogen produces more heat than any other known substance, weight for weight. It is 14.5 times lighter than air, and is the lightest substance so far known. It is almost insoluble in alcohol, and at a temperature of — 240° C and a pressure of 650 atmospheres, it has been liquefied to a steel-blue liquid. It has not been permanently lic^uefied, however, and is practically the only gas that has not been so condensed. Its boiling-point is stated as — 243° C, and its critical temperature, — 233° C. It is the best conductor of heat and electricity among the gase'^ 20 PHARMACEUTIC CHEMISTRY. It is very diffusible, passing through most glasses slowly, but is chemically inactive under ordinary conditions. It is nonpoisonous, but will not support respiration of animals. It will readily unite acids with other elements at the moment of its formation (nascent state). Its use in nature is to assist in formation of water and of vegetable and animal tissues. In the arts hydrogen is used for heating and illuminating purposes, as a lifting power in balloons, etc., but its uses are quite limited. The oxyhydro- gen blcnvpipe offers a means of employing its great heat value (3000° C). In the laboratory it is the ideal reducing agent, and is widely used as such. Compounds. — With oxygen it forms hydrogen monoxid— water, HjO. (For description of waters, see Chapter VI.) It also forms hydrogen peroxid, H2O2, a colorless, odorless liquid with an astringent taste which acts as an oxidizing agent, but may also act as a reducing agent. Hydrogen dioxid (peroxid) decomposes readily, even spontaneously, and is now best preserved by adding 0.2 % of acetanilid. Used as a . bleaching agent, disinfectant and antiseptic. Also as a cleansing and oxidizing agent. OXYGEN. History. — O.xygen was iiuk'pcndcn(I\ discovered ])y Priestley in England in 1774 and by Scheele in Sweden at the same time, thougli Scheele's results were not ]>ublished until 1775. Priestley was heating some red mercuric oxid under a reading-glass by concentrating the sun's ravs upon it, when it changed to metallic mercury and liberated a gas. He called this gas " dephlogisti- cated air," Scheele obtain. d his oxygen by heating "braunstein " (dioxid of manganese), and called it "empyreal air" on account of its power of support- ing combustion. A few years later, Lavoisier proved both gases to be identical and applied the present name oxygen (the name meaning — produc'ng sour), from the erroneous idea he had, that oxygen was necessary to acid production. Occurrence. — Oxygen is present in the air mixed with about four times its volume of nitrogen and other gases. Combined, it is the most abundant element, com- posing f of water and almost § of rocks composing the earth's crust, also in vegetable and animal tissues. It is present in nearly all natural substances and almost everywhere. Preparation. — (i) By heating red mercuric oxid. 2HgO + heat = 2Hg + ©3. (2) By heating black oxid of manganese. 3Mn02 + heat = MngO^ -|- Oj. (3) By heating potassium chlorate. 2KCIO3 + heat = 2KCI + 3O2. If manganese dioxid and potassium chlorate are mixed and heated, the oxygen is given off at a much lower temperature, the potassium chlorate giving up the oxygen, the manganese dioxid re- 22 PHARMACEUTIC CHEMISTRY. maining unchanged, merely acting as a catalyzing agent. Catalytics enhance chemical reaction with- out themselves becoming involved in it. (4) 2KCIO3 + 2Mn02 = 2KMnO, + CI, + O^. (5) 2KMnO, = KjMnO, + MnO^ + O^." (6) K^MnO, + CI, = 2KCI + MnOs + O,. Physical Properties. — Oxygen is a colorless, taste- less and odorless gas. It is slightly heavier than air and 16 times as heavy as hydrogen. One liter of the gas under standard conditions weighs 1.43028 gms. It is slightly soluble in water, thus affording the oxygen for the respiration of water animals and plants. Oxygen can be liquefied under reduced temperatures and increased pressure. It does not burn, but supports combustion. Unites with all elements but fluorin, forming oxids of three classes. Acid oxids are those which, when added to water, produce acids. Basic oxids are those which, when water is added, produce bases. Neutral oxids do not form either bases or acids with water. Examples: (i) PP, + 3H2O = 2H3PO, (2) BaO + H2O = Ba(OH),. (3) MnOj + H20= iio change. Oxygen possesses very powerful ])roperties chemi- cally. Most of the natural atmospheric changes are due to oxygen. Its chief function is to support combustion. The greatest type of combustion is that of respiration — in which we take air into the lungs, separate the oxygen and eliminate it from the body in the form of OZONE. 2^ carbon dioxid, CO^. It assists in the Inirning up of waste tissues in the blood. Chemically, oxygen is the typical oxygenizing agent. It is used in the oxyhydrogen blowpipe to produce intense heat, and with lime, intense light. Oxygen plays its part medicinally as a stimulant and tonic. Ozone is an allotropic form of oxygen. Ozone was discovered in 1785 by Von Marum and called electrified oxygen. Schonbren in 1840 deter- mined its composition. When air or oxygen is exposed to the action of elec- tric sparks, it undergoes a peculiar change, acquiring a strong, pungent odor, contracting in volume and ex- hibiting other new properties. Ozone may also be obtained by several other means. It has a density of 24, a molecular weight of 48, and is represented by the graphic formula: o\ I o = o, 0/ It is present in the atmosphere one part in 700,000. The peculiar power that certain elements thus have of assuming more than one form is known as allotropy. The properties of ozone are those of oxygen, but intensified. Preparation. — (i) By subjecting oxygen to low temperature and high pressure: 3Q2 ^ 203 oxygen ozone 24 PHARMACEUTIC CHEMISTRY. (2) In dilute form, by acting with .stron,!:f sulfuric acid on barium dioxid: sBaO, O, r -/. .. + 3H,SO, =3BaSO, + 3H,0 + — barium dioxid "^ ' ' "^ 4 1 .) 2 ozone. The compound of o.xvgen and hydrogen constitute.s water. H^O, which will be discussed in Chapter VI. NITROGEN. A gaseous element. Symbol, N. Atomic weight, 14. Valence, 3 or 5. Density, 14. One liter weighs 1.256 grams. Occurrence. — Nitrogen exists free in the air mixed with oxygen, argon, etc. ; also free in the gases of the stomach, intestines, blood, urine, etc. Combined, it occurs as nitrates of potassium, sodium and calcium in animal and vegetable tissue and in ammonia com- pounds. History. — It was discovered in 1 772 by Rutherford, who called it "mephitic air" (meaning poisonous to life) . Lavoisier called it azote for the same reason. Scheele first recognized it as a constituent of air. The jjresent name, nitrogen, was suggested by Chaptal,on account of its being a constituent of niter, hence a "niter producer." Properties. — Nitrogen is a colorless, odorless, taste- less, invisible gas;neither combustible nor a supporter of combustit)n; nonpoisonous, will not support life. Soluble in water, lighter than air; chemically very inert. l'r€ptiratioH. — {\) By burning phospliorus in air. 2P, 4- Air 5(4 N, + O2) = 2IV)., + 20N NITROGEN. 25 The P2O5 (phosphoric anhydrid) is then absorbed by water, the impure nitrogen remaining. (2) By heating ammonium nitri:e to decomposition. NH4NO2 + heat = 2H2O + Nj. The nitrogen so obtained being pure. Function. — To dilute the oxygen of the air, to as- sist in plant growth and animal-tissue formation and is of great value in many ways in the form of its com- pounds of nitrogen. With hydrogen it forms Ammonia, NH3. A colorless, pungent, irrespirable gas, freely solu- ble in water, lighter than air, liquetied easily, it emulsifies, but does not saponify fats. Ammonia is found usually in very small quantities, but universally distributed in the atmosphere, rain water, soil, sewer gases, urine, etc. It is produced naturally by dissociation of organic compounds of nitrogen by the action of bacteria. Its chief com- mercial source is the "ammoniacal liquor" from gas-works. With oxygen it forms five oxids: (i) Nitrous oxid, N2O. Laughing gas. (2) Nitric oxid, N2O2. (3) Nitrogen trioxid, N2O3. Nitrous anhydrid. (4) Nitrogen tetroxid, N2O4. (5) Nitrogen pentoxid, N2O5. Nitric anhydrid. The important oxids are NjO, NjO, and N2O5— these forming the following oxacids: (i) N2O + H2O = 2HNO. Hyponitrous acid. (2) N2O3 + H2O = 2HNO2. Nitrous acid. (3) N2O5 + H2O = 2HNO3. Nitric acid. 26 PHARMACEUTIC CHEMISTRY. The most im])ortant of these latter compounds is nitric acid and from it the others are obtainable. It will be fully described under Acids, Chapter VIII. Nitrogen monoxid, N^O, discovered by Priestley in 1793. A colorless, odorless, nearly tasteless gas. Incombustible, but supporting combustion, respirable to a limited extent. Obtained by heating ammonium nitrate: NH,N03 + heat = 2H2O + N^O. Used as an anesthetic in dentistry and minor surgery since 1845. Nitrogen trioxid, NjOg, unites with water to form nitrous acid and hence produces nitrites in natural combination. It has been proven not to exist in a gaseous condition, but to consist of a mixture of nitrogen oxids. Nitric anhydrid or nitrogen pentoxid, NjOj is a white, solid substance at low temperatures and decomposes at 45 °, evolving brown fumes of N2O3. When added to water, it produces nitric acid, HNO3, called aqua jortis (strong water). CARBON. A solid, multiform element. Symbol, C. Atomic weight, 12. Valence, 4. Occurrence. — Found both free and in comljination. All carbon except the incomjjustible owes its origin to animal or vegetable life. Free, it is found in three distinct forms: (1) diamond, (2) graphite, (3) amorphous carbon. All varieties are insoluble and infusible, l)ut readily com- CARBON. 27 bustible, having a strong affinity at high temperatures for oxygen, and burning to form COj. All but the diamond are good conductors of electricity. (i) Diamond. — This is pure carbon when colorless; but with certain small quantities of impurities present, the color may be found to be yellow, blue or even black. It is found in but few places, the most im- portant being the South African diamond fields of Kimberley, where it occurs in a blue cement rock filling the craters of extinct volcanoes. It is also found in some meteorites and very small crystals have been obtained artificially. It is probably due to vegetable origin, the change taking place at intense temperature and great press- ure during great length of time. It is the hardest of all substances known, hence finds much use as a cutting and grinding material. The brilliancy as a gem is due to its high refractive power. The diamond itself is cut or polished by the use of dia- mond powder. (2) Graphite, also called plumbago and black lead, is pure carbon of vegetable origin crystalliz-'ng in six-sided plates. Found in largest quantities in Cey- lon and New York State. Is black in color, lustrous, and is used for lead-pencils, lubricants, cruciWes, stove polishes and for electrotyping, is infusible and not easily burned. In crucibles, pencils, etc., it is mixed with varying proportions of clay. It is made artificially by heating coal mixed with powdered iron ore to a very high temperature by means of the electric current. 28 PHARMACEUTIC CHEMISTRY. The amorphous forms are obtained artitkially in the form of coke, charcoal, l)oth animal and wood, and lami)hlack or oil charcoal. The amorphous jonns of carbon: Naturally, we find these forms of coal all of vegetable origin resulting from the effect of enormous pressure and heat, accomjmnicd by a peculiar fermentation, by means of which the oxygen and other elements have been nearly driven off, leaving nearly pure carbon. In anthracite the process has progressed much farther than in bituminous coal, and is nearly pure carbon with small quantities of hydrogen and o.xygen. Bituminous coal contains considerable hydrocarbon compounds. Cannel coal is a resinous variety. Lignite is still more recent and shows even the cellular structure of the wood which was its origin. Peat is partially decomposed moss. Petroleum contains compounds of carbon and hydrogen. It is quite largely distributed throughout the world. It varies very much in appearance and properties, but is usually dark in color and very odor- ous, often due to sulfur and nitrogen compounds. Artificially, we obtain im])urc carbon, as charcoal, of several forms: (i) Charcoal. — Wood charcoal, obtained by burn- ing wood with insufficient supply of o.xygen, whereby the most readily combustible materials are burned, leaving about 19% of nearly pure carbon. Animal charcoal is similarly made by combustion of bone and CARBON. 29 is known as Ijone-black, drop-bla'.k, but contains only about 10% of carbon, the rest being bone-ash, or calcium phosphate, used in sugar refining. Coke is made by a similar combustion or distillation of coal, used for iron making. The by-products of coke manufacturing are now separated and find large commercial value. Lamp-black is prepared by insufficient combustion of petroleum, gas or similar organic substances. It is used as a black pigment, especially in printers' ink, which consists of lamp-black, linseed oil and soap as its chief ingredients. In combination, carbon is also present in carbo- nates, bicarbonates, carbon dioxid gas and in all organic substances, whether of animal or vegetable origin. Compounds with oxygen: Carbon monoxid gas, CO, not native, colorless, slight odor, very poison- ous. Nonsupporter of combustion, combustible, slightly soluble in water. Prepared from oxalic acid: H2C2O, -f H2SO, = H2SO, + H2O + CO2 + CO. Carbon dioxid, or anhydrid, CO,, is a colorless, odorless gas, soluble in water, nonsupporter of com- bustion and incombustible. Occurs free in air and many waters, and is formed during respiration, com- bustion, decay and most fermentations. With water it is supposed to form carbonic acid, which is very unstable: H/:) -K CO, = H2CO3. The carbonates of the metals are very important 30 PHARMACEUTIC CHEMISTRY. and very abundant. Carbon dioxid is usually pre- pared from marble: CaCOj + HjSO, = CaSO, + H.O + CO,. Preparations of C with nitrogen we have the cyano- gen compounds — very poisonous: CjN,, cyanogen is a colorless gas, with a characteristic odor, combustible with a pink flame; HCN, or prussic acid, a liquid, colorless, volatile, feeble acid, with odor of bitter almonds, prepared by acting on potassium cyanid w'ith dilute sulfuric acid: 2KCN + H^SO, + HjO = K^SO, + H^O + 2HCN. Acid hydrocyanic dilute, U. S. P., contains 2% ab- solute HCN. Scheele's prussic acid contains 4%. CHAPTER IV. THE HALOGEN ELEMENTS. The halogen group is so named because of the close resemblance between their sodium salts and sea salt, the term halogen signifying "salt producer." The group comprises iodin, chlorin, bromin and fluorin, which in their general characteristics strongly resemble each other and readily change places in combinations without producing any very marked change in the character of the compound. They are electronegative, fluorin being most strongly so and iodin the least so. They have a characteristic pungent odor and act as disinfectants and bleaching agents. They exhibit a regular physical gradation with increase in atomic weight. Thus fluorin and chlorin are gases, bromin is a liquid and iodin is a solid under normal conditions. Chemically, they show the same graduation of change; with hydrogen, fluorin unites instantly and so eagerly as to produce explosion by mere con- tact, even in the dark. Chlorin will not unite with hydrogen except in the light, but in direct sunlight does so rapidly, producing explosive tendencies. Bromin vapor requires a flame to produce union with hydrogen, and iodin vapor and hydrogen re- quire to be strongly heated in contact with spongy platinum. 31 32 IHfARMACKUTIC CHEMISTRY. With oxygen they unite quite difficultly and in inverse order. The compounds formed are rather unstable. Bromin and fluorin have no oxids. Fluorin produces no oxacids or salts. Thus, the compounds formed are: Hydracids. Oxids. Oxacids. HF: HCl: CKO CUO, CI2O5: HCIO HCIO, HCIO, HCIO4 HBr: HBrO HBrOa HBr04 HI: I2O,, LO,: HIO HIO. HIO3 HTO4 FLUORIN. Fluorin is the typical group clement: \'alcncc, 1. Density, 19. Atomic weight, 19. Specific gravity, 1.3. History. — Very recent in its discovery, for it was not possible to isolate it until 1886, when Moissan finally succeeded. He obtained fluorin by passing an electric current through a solution of jxjtas- sium fluorid, FK, in anhydrous hydrofluoric acid, HF. Fluorin he separated at the anode, with hydro- gen at the cathode, the reactions taking place thus, the breaking up of the acid potassium fluorid: 2HFKF = F2 + 2HFK, The reaction is carried out in a U-tube of platinum- iridium, this being acted ui)on less than platinum alone. Occurreme. — Fluorin occurs in combination in considerable quantities as native Jhior-spar, C^Y^, and in cryolite, NagAIFo, and other similar com- pounds; also in small amounts in bono, tooth enamel and .'^ome mineral waters. Properties. — Of all known eloments, tUiorin is the most active, due to its intense chemiial aftinities. FLUORIN. 33 It resisted long any attempt to isolate it, for if liberated, it instantly recombined with the materials of the vessel in which the separation was made. It appears to be a colorless gas, with a character- istic irritating odor; but even this is of doubtful truth, for with the moisture of the air or of the mucous membranes hydrofluoric acid is instantly produced, hence the true odor of fluorin is not certainly known. All metals, even gold and platinum, are acted on by fluorin to a greater or less extent and organic com- pounds are attacked violently. At a temperature of — 185°, it condenses to a liquid condition. This was obtained also by Moissan and Dewar in 1897. The liquid is a yellowish, mobile fluid, having no action on silicon, phosphorus, sulfur or glass. It attacks, however, hydrogen and hydrocarbons freely, combining violently with all elements except oxygen, nitrogen and chlorin. Compounds. — Hydrogen fluorid or hydrofluoric acid is prepared by the action of strong sulfuric acid on calcium fluorid, thus: CaF^ + H^SO, = CaSO^ + 2HF. The gaseous acid is passed into water in leaden, wax or gutta-percha bottles as it attacks glass. The anhydrous acid is prepared by heating acid potas- sium fluorid in platinum retorts, thus: HFKF = KF -f HF. It is a colorless, limpid, fuming liquid, boiling at 19° C. It is used as a solvent of glass in etching, etc. It is exceedingly dangerous to handle, for it produces not only irritati(;n to m.ucous surfaces, but 3 34 PHARMACEUTIC CHEMISTRY. severe burns upon the ilesh and often serious con stitutional symptoms and death. CHLORIN. At. \vt., 35.5. Valence, 1-3-5-7. Sp. gr., 2.47. Density, 35.4. Symbol, CI. History. — Discovered by Scheele in 1774 and thought to be a compound of oxygen and hydro- chloric acid. He called it "dephlogisticated m.arine acid gas," for hydrochloric acid was then known as "marine acid." In 1810, Davy gave it the name chlorin, on account of its greenish-yellow color. Occurrence. — Always in combination and ver\- abundantly. The most common form being sodium chlorid. Preparation. — (i) By action of hydrochloric acid on manganese dioxid. MnOj + 4HCI = MnCl^ + 2H2O + 2 CI. (2) By action of sulfuric acid on manganese dioxid and sodium chlorid. 2NaCl + MnO, -f- 2H,SO, = Na.SO, -H MnSO,+ 2H20-t-2Cl. (3) Slowly generated when moistened chlorinated lime is exposed to the air. CO2 -f CaO(Cl)2 = CaCOg -\- CI,. Properties. — A greenish-yellow gas 2.5 times as heavy as air, pungent and suflfocating odor. Irre- spirable, irritating, soluble in water. One volume of water at 10° C. dissolves 3 volumes of gas. Li(|Uor ( hlori conipositus. U. S. 1'., is a 0.4''^ solution. Li(|uid chlorin is now a comnu-rcia! arliile and is BROMIN. 35 used in extractiun of gold from its ores. Sp.gr. 1.33; boils at 33.6° C. Chemically, chlorin is very active and especially noted for its affinity for hydrogen and the metals with which it forms chlorids. Burns in an atmos- phere of hydrogen. Its allotropic form is similar in appearance, but is inactive. It is prepared in the dark. The well-known bleaching property of chlorin depends upon its affinity for hydrogen, it decomposes the moisture liberating oxygen which in its nascent state energetically decomposes the coloring matters. Chlorin will net bleach a perfectly dry substance. Compounds. — With oxygen — none important: CI2O, chlorin monoxid. CI2O3, chlorin trioxid. CI2O4, chlorin tetroxid. With oxvgen and hydrogen it forms the acids of chlorin: HCl, hydrochloric acid, a hydracid. HCIO, hypochlorous acid. HCIO2, chlorous acid. HCIO3, chloric acid. HCIO4, perchloric acid. The important acids are HCl, HCIO, HCIO3 and will be further discussed in Chapter VIII. BROMIN. Symbol, Br. At. wt.. 70.76. Sp. gr., 2.99. Va- lence, I. i/w/ory.— Discovered by Balard (1826), in the sea-water after crystallizing out the salt from con- oxacid^ 36 PHARMACEUTIC CHEMISTRY. centrated solution. He gave it the name bromin (bromos, signifying a stench), on account of its dis- agreeable odor. Occurrence. — Never free in nature. Chiefly com- bined with the alkaline metals and magnesium in sea-water and in many saline and salt springs. The saline deposits of Stassfurt contribute a large part of our bromin supply. Preparation. — Sea -water, or other saline brine, is evaporated and several crops of the less soluble materials collected. The final liquid known as "bittern," is treated with chlorin gas which liber- ates bromin, thus: MgBr, -h CI, = MgCl, + Br,. This is then shaken out with ether, removed, treated with potassium hydroxid and evaporated to dryness, leaving potassium bromid and bromate. This is then treated with manganese dioxid and sulfuric acid, liberating pure bromin. 2KBr + MnO, -f 2H,SO, = K,SO, -F MnSO,-|- 2H2O -^- Br,. Properties. — A heavy, dark-red, mobile liquid, evolving at ordinary temperature a reddish, irrita- ting, pungent odored gas. Soluble in thirty parts of water and readily soluble in alcohol, ether and chloroform. Chemical properties similar, but weaker than those of chlorin. Poisonous. Recognized by its color and by its odor, also by the yellow color of its solutions. Is separated from its compounds by chlorin, and may I)e so identified. Tmpurily iisua'l\- present is l)romin clilorid, UrCi. lODIN. 37 Compounds. — Similar to chlorin compounds, but less stable. Hydrogen bromid or hydrobromic acid, HBr, is made by action of potassium bromid and tartaric acid. KBr + H^C.H.Og == HBr + KHC,H/)e. See chapter on Acids, page 71. lODIN. Symbol, I. At. wt.. 126.54. Sp. gr., 4.95. Val- ence, I. History. — In 1812, Courtois was endeavoring to prepare niter from the ashes of sea -weeds. He no- ticed the beautiful violet-colored vapors. It remained for Guy Lussac, however, to investigate it later on. It derives its names from the color of its vapor. Occurrence. — Similar to the other members of this group, it is never found in nature asanuncom- bined element. It is associated with the alkali metals, with magnesium and calcium. Found in niter beds, in sea and mineral spring waters, but most largely in certain sea-weeds collected off the coast of Scotland and France, and from the ash of these weeds our commercial supply largely comes. This ash is obtained at as low a temperature as pos- sible and is known as "kelp." For laboratory uses iodin can be obtained in the same manner as chlorin, thus: 2KI + MnOj + 2H2SO, = K^SO, + MnSO,+ 2H2O + \,. Properties. — A bluish -black, shining crystalline 38 I'lIARMACKUTIC CHEMISTRY. solid. Crystallizes in scales or tablets, emitting an irritating vapor. Melts at 114° C. It is poisonous, and used as external anodyne. Its salts are altera- tive when used internally. Free iodin turns starch paste blue and may be rendered free from its compounds by chlorin gas. Acetate of lead gives a yellow precipitate of lead iodid with compounds of iodin; The preparations in common use medicinally, are: tincture iodin, a 7% alcoholic solution, containing potassium iodid; Liquor iodi compositus {Lugol's solution) solution, of iodin and potassium iodid in water: 5 gms. iodin, 10 gms. potassium iodid, in 100 gms. of the solution; Hydr iodic acid, HI, made by passing hydrogen sulfid gas through an iodin solution. I2 -f H^S = 2HI + S. Syrup hydriodic acid contains 1% HI. Made by reaction of potassium iodid and tartaric acid in alcoholic solution. KI + HAH^Oe = KHC.HPo + HI. The chemical compounds are similar to those of bromin, but fewer in number and less stable. CHAPTER V. THE SULFUR GROUP. The sulfur group consists of sulfur, silicon, phos- phorus, boron, selenium and tellurium. The im- portant members of this group are sulfur, phos- phorus and boron. Silicon is worthy of some consideration, while selenium and tellurium are of little importance to the pharmaceutic chemist. Sulfur, as the most important, will be considered first. SULFUR. Symbol, S. Sp. gr., 2. At. vvt., 31.85. Melts at 115° c. History. — Sulfur was known to the ancients. Occurrence. — Occurs free in volcanic areas, and our most important source has long been Sicily and Italy. Large deposits are found in Iceland, China, India, California and the Rocky Mountain districts. It usually occurs mixed with clay, from which it may be separated by distillation. Beds are found some- times in which the sulfur is constantly being formed, due to chemical changes, and such beds are called "sulfatara." It is also found in many ores in combination with metals, as sulfids and sulfates, also in many min- eral springs, both free and as sulfids, sulfates or 39 40 I'flARMACEUTIC CHEMISTRY. even as sulfuric acid; also in many organic ]>!anl and animal bodies. Properties. — Sulfur, when pure, is a solid, pale yellow, dimorphous, with several amorphous modifi- cations. Melts at 115° C, boils at 448° C. Brittle, nearly tasteless and odorless, nonconductor of heat and electricity. Insoluble in water, and almost so in alcohol; best solvent is carbon disulfid, 100 parts of which dissolves 37 parts of sulfur. In relation to its forms, sulfur may be divided into two classes: A. Those soluble in carbon disuliid. A. (i) Yellow, opaque, rhombic octahedra. (2) Long, transparent, needle-shaped prisms; these return to the octahedra after a few days' exposure. (3) A variety of lac sulfur, prepared by acting on alkaline polysulfids with a mineral acid. B. Those insoluble in carbon disulfid. B. (i) A tenacious, amorjjhous mass, obtained by pouring sulfur heated to 230° C. into cold water. (2) A variety of lac sulfur prepared by acting on a thiosulfate with dilute mineral acid, or along with flowers of sulfur that are suddenly cooled. Preparation. — Nearly all obtained from native sulfur by distillation. A small amount from iron pyrites. In laboratory practice it may be prepared by several means, such as the reaction of hydrogen sulfid and sulfur dioxid: 2H,S + S()2 = 2H2O + 3S. Also by Imrning h}drogen sulfid with insuflaiont supply of air, thus: 2H2S 4- O = HjO + S.,. SULFUR. 41 Sulfur is also a by-product in smelting of copper pyrite and in the vat waste of the LeBlanc process of preparing sodium carbonate. Official sulfurs and preparations: Sublimed sul- fur, flowers of sulfur, obtained by vaporizing and condensing sulfur. This is not pure, contains possi- ble impurities and sulfurous and even sulfuric acid. In order to insure purity, it is treated with ammonia water, which neutralises the sulfur acids, removes the arsenic which it dissolves out, and other im- purities and produces a pure sulfur. This is known as washed siiljur, and is preferred by many for medicinal purposes. Precipitated suljur is lighter, more easily sus- pended in liquids and hence preferable to the other forms. It is prepared by boiling together sublimed sulfur and lime, filtering and adding hydrochloric acid. 3CaO + 3S2 = 2CaS2 + CaS^Og. calcium thiosulfate 2CaS2 + CaSjOg + 6HC1 = 3S2 -f aCaCl^ + 3HO2. The precipitated sulfur is thoroughly washed with water. If sulfuric acid is used in place of the hydrochloric acid, the precipitate is contaminated with calcium sulfate, and it then goes by the name of "milk" or "lac sulfur." Sulju/ iodid is prepared by rubbing together sulfur and iodin and heating.. The product is in the form of a grayish-black solid and is quite unstable and decomposes readily. 42 I'HARMACEUTIC CHEMISTRY. Compounds. — With hydrogen : Hydros id j uric acid, HjS, also called hydrogen sulfid or sulfuretted hydrogen. A strong colorless gas, of characteristic odor, soluljle in water, produced naturally in organic decay when sulfur is present Also found in many mineral springs. May be pre- pared by acting on iron sulfid with dilute sulfuric acid. FeS + H,SO, = H,S + FeSO,. With oxygen: Sulfur dioxid, SO., = sulfurous anhydrid. Sulfur trioxid, SO3 = sulfuric anhydrid. With oxygen and hydrogen: H^SOj, hyposulfurous acid. ■ H2SO3, sulfurous acid. HjSO^, sulfuric acid. H2S2O3, thiosulfuric acid. H2S2O7, pyrosulfuric acid. H^SjOg, dithionic acid. HjSgOg, trithionic acid. HjS^Og, tetrathionic acid. HjSgOg, pentathionic acid. The important ones arc sulfuric, thiosulfuric and pyrosulfuric, which will be discussed under Acids, Chapter VIII. PHOSPHORUS. Symbol, P. At. wt., 31.- Sp. gr., 1.83 at. 10° C. History. — Phosphorus was -discovered by Brandt, of Hamburg, in 1669, in urine; by Hoyle in 1680, b\ a secret process; in 1769, by Gohn, in bones; and until /^ >-^ OF THE ^ I UNIVERSITY I 1 77 1, when Scheele published a method of obtaining it from bone ash, phosphorus was considered a chemi- cal curiosity. Occurrence. — It has never been found free in nature; in combination it is most common as calcium phos- phate, Ca3(POj2, a mineral derived from the bones of the prehistoric mammals. Occurs in soils and in animal bones, tissue and blood. Also in plants to which it is also essential. Properties. — Elementary phosphorus is a solid occurring in two forms: (i) Yellow phosphorus, soft and flexible, insoluble in water, soluble in oils and carbon disulfid. Poisonous, volatile and inflam- mable, even at low temperatures, fusible and lumi- nous in the dark. Combines readily with oxygen. (2) Red or amorphous phosphorus, opaque, in- soluble in carbon disulfid, infusible and nonlumi- nous and possessing no tendency to combine with oxygen. At a temperature of 260° C, it is changed into ordinary phosphorus and assumes its properties. Red phosphorus is prepared by heating the ordi- nary variety for about 36 hours to a temperature of 250° C. without supply of oxygen. Other varieties have been prepared. The metallic or black form is prepared by heating red phosphorus in a sealed tube to 500° C. It is inert and of no importance. Ordinary phosphorus must be kept under water to prevent spontaneous combustion, its most characteristic property being its ready oxidation. Preparation. — Phosphorus is obtained from cal- 44 PilARMAtEUTlC CHKMISTKY. fined bones by adding sullurif acid, liltering, re- moving the calcium sulfate; the liquid eva[)orated, and residue distilled with charcoal, thus: (i) Ca3(PO,)2 + 2H,SO, = 2CaSO,+ CaH,(POJ,. calcium hydrogen phosphate. (2) 3CaH,(P0,), + loC = Ca,(PO J-A + 2P3 + 6H2O + loCO. ^^•'^^'""^ phosphate Compounds. — With hydrogen : PH3, phosphorus trihydrid, phosphoric or phos- phoretted hydrogen, phosphin, is a colorless, poison- ous gas, inflammable, odorous, resembles ammonia to some extent in its chemical properties, but is much weaker in alkalinity. With oxygen: P._;03, phosphorus trioxid or ])hosphorous anhy- drid. P2O5, phosphorus pentoxid or phosphoric onhy- drid. With oxygen and hydrogen: Acids of phosphorus. HPH2O2, hypophosphorous acid. . H.,PHO, H3PO, HPO3, metaphosphoric acid. (H3PO, — H,0=HP03). H^PgOj, pyrophosphoric acid. (2H3PO, — HjO^H^P-AV The important acids are the last three, all derived from phosphoric anhydrid, thus: (i) P2O5 + HjO = 2HPO3, metaphosphoric acid. BORON. • 45 (2) P2O5 + 2H2O = H^PjOy, pyrophosphoric acid. (3) P2O5 + 3H2O = 2H3PO4, orthophosphoric acid. The orthophosphoric acid is the most important and is the one meant by "phosphoric acid." It is a liquid, the other two being solid. The meta acid is known as "glacial" phosphoric acid. BORON. Symbol, B. At. wt., 11. Valence, 3. It is never found native in the free state, but maybe prepared in two allotropic states, first as a greenish- brown powder; second, as a crystalline solid of vary- ing colors, ranging from colorless to garnet. Occurrence. — It is found in combination with cal- cium, magnesium and sodium as borates, the latter the most important, and known as borax, is found in India and California. .As boric acid it is found in Tuscany. Boric acid is prepared from the borate bv the action of hydrochloric acid, thus: " Na^B^O; ioH,6 + 2HCI = aNaCl + 4H3BO, + 5H2O'. Boric acid separates in white, shining scales, is soluble in 2 5 parts of water and 3 parts boiling water, is a weak acid. A strip of turmeric paper dipped in a solution of boric acid turns cherry-red on drying. Boric acid finds use as a mild antiseptic and deter- gent. Boric acid and its salts are poisonous to lower animals and plants and have produced serious conditions in human beings following its use too freelv. 46 PHARMACEUTIC CHEMISTRY. SILICON. Symbol, Si. At. \vt., 28. Valence, 2 and 4. Occurrence. — Never found native, but may be pre- pared in three allotropic states — amorphous, graphitic and crystalline, somewhat resembling the three states of carbon. This element, next to oxygen, is the most abundant element in nature. It is found combined with oxygen as silica, Si02, in quartz, sand, flint and many minerals. Clays are principally silicates of aluminum colored by iron or other mineral or vege- table matter. Neither the element nor its compounds are of much interest to the pharmaceutic student. Compounds. — Silicic hydrid, SiH4, also bromid, SiBr^, and fluorid, SiF^, are known. SiO,, silicic oxid is the only oxid of this element, known as "silica," a solid, tasteless, odorless, when freshly prepared, soluble in water, attacked only by hydro- fluoric acid, and almost infusible by itself. Found in all granitic rocks which are composed of quartz, feldspar and mica. Quartz is almost pure silica, as also are sands and agates, the latter being a colloidal form deposited from silicious water. This silicious water is the chief agent in petrification. Silica forms the skeleton of certain invertebrate animals, is found in stems of plants, and hydrated it forms the opal. When silica is fused with alkali carbonates or hy- droxids, it forms silicates with these metals or a form of glass, ihc most important being the insoluble glass, silicates of sodium, potassium, lead or calcium or combinations of these wilh an exiess of silica present. SILICON. 47 Soluble glass is similarly made, but with an excess of the sodium or potassium. This product is also known as "water glass." Silicic acid may be prepared by acting upon a dilute solution of an alkaline silicate with hydro- chloric acid. It is only found in water solutions and is very unstable. SELENIUM.— Symbol, Se. Valence, 2. At. wt., 78.87. TELLURIUM.— Symbol, Te. Valence, 2. At. wt., 125. These elements are called "rare" and are of little importance to the pharmaceutic student. They are found associated with sulfur and form acids similar to sulfurous and sulfuric acids. CHAPTER VI. WATER. Symbol, H,0. Mol. wt., 17.96. History. — Until 1781 water was considered to be an element. At that time Cavendish proved its composition by synthesis. Priestley had also found that when hydrogen and oxygen were combined by explosion moisture was formed, but Cavendish first produced a sufficient amount of moisture to prove its identity. In 1805, Humboldt and Guy Lussac determined the ratio of its constituents. Occurrence. — Water is so widely distributed that it may be said to be almost universal. It exists in three states of aggregation: Below 0° C, it occurs as a solid; between 0° C. and 100° C, it takes the normal state of a liquid, and above 100° C, it exists as a gas or vapor. As gas we have water vapor as a constituent of air under normal conditions. The atmospheric mois- ture is i)roduced by spontaneous evaporation, of both the land and water surfaces; from the forma- tion of steam in manufacturing processes, respiration of animals and plants, etc. Steam is gaseous water when first prepared, and at a temperature above 100° C. it is colorless and in- visible, but is easily reduced in (emperature. and 4S WATER. 49 what we ordinarily speak of as steam is a condensa- tion of the vapor forming very fine drojjs of water. It is this ])artially or finely condensed moisture that we see in mists, fogs and clouds. In the liquid condition, water is present in im- mense quantities in the ocean, lakes, rivers, smaller streams and as rain and as subterranean waters, soil moisture, etc. It also occurs, though hidden, as water of crystallization in many crystals, minerals, etc., and it is a large constituent of all the vegetable and ani- mal organisms. Thus, many vegetables are over four-fifths water, and over three-fourths the human body consists of water. In the solid state, water occurs as snow, hail, and ice; the two former being modifications of the kil- ter. Snow is, therefore, water congealed in the form of crystals. Hail is an accumulation of layers of ice formed to an irregular globe shape produced by natural precipitation in certain atmospheric currents and ice is also a crystalline congealed water form. At a temperature of o° C, water changes under normal conditions to a solid. As water cools it con- tracts steadily until a temperature of 4° C. is reached, when it begins to expand again until solidi- fication occurs. Cooling then contracts the ice similarly to other solids. Ice, however, is lighter than water, and hence rises or forms at the surface of the water. If this were not true, bodies of water would freeze solid, even to the bottom, and lakes, streams, etc., would require great time and heat to 4 50 PHARMACKUTU: CHEMISTRY. bring them to the liquid state again. Water at 4° C. is at its greatest density and at that temperature is taken as a standard of weight. Water may be classified as follows- Atmi Rain, spheric \ Snow. [ Hail, etc. 1. Springs. 2. Ground. ((/) Sweet ; 3. Well Terrestrial • f Open. ' Driven. [ Artesian. (b) Salt 4. Pond or Lake. 5. River. 1. Ocean. 2. Inland Sea. Mineral Sulfur. Saline. Acidulous. Chalybeate. Alkalin. Alum styptic, Silicious. liorax. Water when pure is a tasteless and odorless liquid. When seen in small quantities it is colorless, but in large masses it appears to be of a greenish or bluish color. This is largely due to the refraction of light rays, though it is thought that very finely divided sus- pended matter is also responsible for color in waters. WATER. 51 Water is a poor conductor of heat and is only very slightly compressible. It is the most important solvent and dissolves a larger number of substances than any other liquid. Owing to this property, no natural waters are found to be strictly pure, for even rain water contains foreign materials dissolved as the rain passes through the air. Atmospheric waters. Rain water, as stated, is impure and may contain more or less of the follow- ing impurities: dust, germs, oxygen, nitrogen, carbon dioxid and ammonia from the air of which they are constituents. Nitric, nitrous and sulfuric acids or- ganic substances, saline matter, ozone and hydrogen peroxid in very small amounts are also found. In spite of this number of possible contaminating materials, rain water is the purest form of natural water and may contain, if collected in the country, an average of about 0.029 parts of foreign matter in 1000 parts of water. Collected in towns or cities, much larger quantities are present. Rain water after reaching the earth becomes at once contaminated with various matters, depending upon the surface upon which it falls and the strata over or through which it may flow. It reappears as ter- restrial water and will be so considered. First, spring water. Is always chemically impure, the nature and quantity depending upon the locality and constituents of the soil, through which it passes. Generally clear, cool and sparkling and hence potable. It usually contains (i) Chlorids, sulfates, bicar- 52 J'HARMAC-EUTIC ClIKMISTKY. bonates of ]H)tasbium, sodium, calcium and magne- sium. (2) Ncarlyalways silica and traces of aluminum and iron. (3) The atmospheric contamination ma- terial before mentioned. (4) Organic decomposition matter and bacteria usually harmless in nature. A property more common to sj^ring water than to other waters is hardness. This may be defined as that ])ropcrly of water which renders the formation of a lather with soa}) difficult. It is due largely to salts of lime, but also to salts of magnesium and iron. If these salts consist of carbonates which can be removed by boiling it, the hardness is known as " Temporary." If due to sulfates, however, boil- ing will not remove them, and it is then known as ' ' Permanent " Hardness. The incrustations forming in boilers, etc., are ])ro- duced by the deposition of these mineral constituents. Temporary hardness crusts can be removed b}- ammonium chlorid, which converts the bicarbon- ates into readily soluble chlorids. Crusts produced by permanently hard waters are not affected by the ammonium chlorid. Numerous boiler com- pounds are on the market for this i)urf)ose, the best of which is trisodium phosphate, Na^PO^. Ground water is water held by the porous strata of the earth's surface as far as the first impervious layer, and has the same properties as the well waters. Well Wafer. — Well waters arc of three types as stated. Thus we have the ()])en or dug well, the driven or drilled well and the artesian well. The first class is supplied with water from sul)lerranean springs or streams or from surface drainage. From the former source the water may contain the materials enumerated under spring water. The surface water supply may contain salts and nitrogenous matter from house drainage, also possible sewage from vaults and cesspools. The much-applauded country well water may, un- less much care is taken in its location, with relation to buildings, cesspools, vaults, etc., be a concentrated liquid full of infection and filth. Driven wells come in for similar criticism, and much care should be exercised in selecting their location. Artesiin or deep strata wells are usually free from surface and organic impurities, but often are very heavily laden with mineral matter, and may thus be rendered unfit for potable purposes. Artesian wells, of course, can be obtained only in places where the strata so slope as to form a deep, impervious basin at the center of which the well is drilled. Pond, Lake and River Waters. — These, generally speaking, are purer waters, naturally, than spring waters. Suspended matters are present in running water, but when the water comes to rest these matters are dcfju.'^ited as sediment and the water becomes clear. Streams however, flowing through populous dis- tricts, often become contaminated with sewage, and when used as outlets for city refuse, sewage, manu- facturing waste, etc., they become offensive and dangerous for potable purposes. These organic 54 PHARMACEUTIC CHEMISTRY matters, however, soon liecome oxidized with the oxygen held by the water itself, by the oxygen of the air and the effect of sunlight, and by action of bacteria present, and hence are rendered harmless. Flowing streams are supposed to purify themselves in from 8 to 12 miles, dependent upon the nature of their beds and the rate of flow. This is doubted by some authorities, however, and it is still an open question. Ocean and Inland Sea Waters.— T\\t water of the ocean contains a large amount of sodium chlorid and magnesium chlorid, some potassium, calcium and magnesium sulfates, sodium bromid and traces of other salts. The total average amounts to about 2138 grains (138 gms.) per gallon, of which about 80% is sodium chlorid (common salt). Inland seas contain much larger amounts— the Dead Sea about six times and Great Salt Lake seven times as much solids as the ocean. They also contain several salts not found in ocean water but due to the nature of the soil drained into them. Potassium chlorid and calcium chlorid are examples. Mineral Waters are natural waters which con- tain unusually large quantities of some of the or- dinary impurities or are characterized by unusual constituents; they are named according to their most prominent characteristics, thus: (i) Sulfur water contains sulfur in form of hydro- gen sulfid, metallic sulfids or even free sulfur. They usually also contain other salts. The odor of sul- furetted hydrogen is nearly always noticeable. WATER. ■ 55 Examples: Harrowgate, of England, White Sulfur, of Virginia, and others throughout the United States. (2) Salines, those having a salty taste, are of three classes: (i) Brines, in which sodium chlorid pre- dominates, but usually also contain sodium bromid and iodid. Examples, salt wells of Michigan and springs at Syracuse, N. Y. (2) Bitter, waters, con- taining calcium and magnesium chlorids, as St. Cath- erine Spring, Canada. (3) Purgative waters, contain- ing magnesium or sodium sulfates, as Epsom Spring or Kissingen. Acidulous waters contain sufficient free carbonic acid gas to produce effervescence, as appolinaris, selters, etc. Chalybeates are those with iron present in medic- inal quantities, usually in the form of bicarbonate or sulfate. Alkalin waters are not alkalin when fresh, but if boiled the bicarbonates are changed to carbonates. Other salts generally present. Examples: Saratoga and Vichy waters. Acid waters are those containing free acids, such as hydrochloric or sulfuric. Rio Vinaigre, of South America, contains both. Alum waters contain alum, also, generally, sulfuric acid and iron. Rockbridge and Church Hill Alum Springs, both of Virginia, are examples. Silicious wa ers are those containing considerable silica, usually hot springs. Geysers of Iceland are examples. Borax waters contain borax in quantities profitable 56 i'llAftMACKlTIC rnKMlSTKY. to extract. Certain lakes of Thibet and California come under this class. Artificial mineral waters if well made are of much medicinal value, but often nearly pure spring waters are sold as mineral waters and really have no such value. Potable waters are those that are suitable for drinking purposes, and since these are of such great importance to man and since it has also been proven that waters are a fruitful source of supply of infec- tious diseases, it is essential that waters used for drinking purposes be as pure as possible. No natural waters are pure. Pure water may be obtained by distillation, by rejecting the lirst and last ten per cent, distilled, but even this is not the best potable water. For the best sustenance of the body a potable water should contain a trace of magnesium and calcium salts. As a general thing, small amounts of mineral matters are not injurious to health; and organic matter in itself is not always certainly harmful, but it usually does show sewage or other contamination which might easily carry with it bacterial growths that could produce disease conditions. Chemical analysis, it is true, cannot prove bacteria present, but it can show the constants which, if large, go to indicate prob- able contamination and by this means lead to further investigation. Suspicious waters should always be refused and thorough examination of their source, chances of c(jntamination, etc., made. Waters may be purified by numerous methods: I'OTABLK WATER. 57 On the large scale by open sand filtration beds or by the later percolation spray system. In small house- hold quantities by types of porous porcelain or char- coal filters, etc. Space will not allow of detailed discussion. Usual types of waters called potable may be classi- fied thus: Safe Suspicious Dangerous 1. Spring waters. 2. Deep well waters. 3. Mountain lake or river waters. 1. Stored rain water. 2. Surface water. 1. River water with sewage. 2. Shallow well water. Sewage is always dangerous, due to the liability of pathogenic bacteria being present. Refuse from factories is usually not dangerous in running streams, for the poisonous materials either neutralize each other or are sufficiently diluted to render them harmless. Metallic impurities usually are derived from pipes or tanks. Copper has been known to produce sick- ness. The most common form of sickness is lead poisoning. This is produced by the solvent action of the water, also of the dissolved carbon dioxid on the leaden pipes. Water that has stood for some hours in the leaden pipes should never be used for drinking. Water may be examined for probable purity or contamination as follows: By noticing the taste, 58 PHARMACEI'TIC CHEMISTRY. (xlor, reaction, turlndily and color. It should he negative in all these res})ects. Total residue is ohtained by evaporating a known quantity to dryness. Dissolved solids, by filtering, evaporating and weighing. It may reach 30-50 grains per gallon safely. Non-volatile residue is obtained by igniting the total residue. The loss on ignition shows organic constituents and should not be 50% of the total residue. Hardness determined by Clark's test, which con- sists in using a standard soap solution to make a lather with the water. Small quantities are added with agitation ui.til the lather persists for five minutes. A blank teit must be carried out with distilled water. A water containing not over 50 parts per million of "hardness" is classed as a soft water, one with 150 parts is a hard water. Chlorin is detei mined by the use of standard silver nitrate solution. One hundred cubic centimeters of the w-ater is placed in a white porcelain dish, a few drops of potassium chromate indicator added and silver nitrate solution run in from a burette, drop by drop, till a slight red tint appears. If chlorin is present in very small amounts the water may be re- duced to one-half its bulk by evaporation before titration. Too much dependence should not be placed upon amount of chlorin present, for larger amounts of organic matter may be present and very little chlorin be fou-nd. Also high chlorin present may be due to dissolved chlorids from the soil, WATER- ANALYSIS. 59 hence the characteristics of surroundings should be taken into account in the consideration of potability. Sewage generally contains about ii parts per 100,000, and if conditions do not give reasons for high chlorin, over 5 parts per 100,000 may be considered suspi- ( ious of sewage contamination. Sulfates are determined by precipitation as barium chlorid. Nitrites, by add ng sodium sulfanilate and sulfuric acid, then naphthylamin. Nitrites will de- velop a pink color, the depth dependent upon the quantity of the nitrites present. Nitrates, a simple qualitative test may be made, using diphenylamin in concentrated sulfuric acid. A deep blue indicates nitrates or nitrites. Quantita- tively, nitrates may be tested by using sulfanilic acid and naphthylam.in hydrochlorid. Free ammonia is determined by use of Nessler's reagent in standard tubes for reading the color pro- duced. Ammonia also exists combined and known as albuminoid ammonia. Water is first made alkalin with fixed alkali and distilled; the result is the amount of free ammonia. Permanganate of potas- sium is now added to the retort and further portions distilled over. The permanganate breaks down the albuminoids and ammonia is formed, which is distilled over and Nesslerized. A good water should not contain more than o.i parts of free ammonia or 0.15 of albuminoid ammonia in one million parts of water examined. Organic matter is determined by the oxygen consuming power as measured by the amount 6o IM1A1S^ . H— 0/ ^O Oil of vitriol. Hydrogen sulfate. Obtained from pvrites, FeS, by heating, forming sulfurous anhydrid, oxidizing and hydrating this to sulfuric acid. (i) S, + 20/= 2SO.,. (2) 2HNO, + 3SO, = 3SO., + H.O + X.,0. (3) SO^ + H,.0 = H.,SO,. DIBASIC ACIDS. 73 Chamber acid has a specific gravity of 1.55. Pan acid has a specific gravity of 1.74 = 78%. Concentrated acid lias a specific gravity of 1.83 = 92.5 %• It is an oily, heavy, corrosive acid, colorless if pure, colored brown if impure. Dilute sulfuric acid U. S. P. contains 10% sulfuric acid. Aromatic sulfuric acid contains 18.5% absolute or 20% U. S. P. sulfuric acid, combined with alcohol and aromatic tinctures. Thiflsuljityic Acid, HjS.^Og )(S^ - H— S^ ^"O. Not found in tlie acid form, Init the salts are used. — ) H — O. '^O — O Pvrosidfuric Acid, H.S^O,. ^Sf | H — S^ ^0 — Nord Hansen sulfuric acid, a heavy, browui, oily liquid, thought to be a solution of SO3 in HjSO^. H— O. Carbonic Acid, H2CO3. ^(C = O). H — Q/ Important only for its salts, the carbonates and bicarbonates. Unstable, feeble acid. Easily decom- posed, forming carbon dioxid, CO,, and water, HgO. H — O. .H Phosphorous Acid, H3PO3. /^C • H — O^ ^O A colorless liquid, easily oxidized, its salts are known as phosphites. 74 PHARMACEUTIC CHEMISTRY. TRIBASIC ACIDS. (These Form Three Types of Salts — Normal, Acid and Double.) H - 0\ Arsenous Acid, H.AsOj. H — O— (As). H — O/ Prepared by roasting arsenic ores, which produces the arsenous oxid, AsOg, which is the most impor- tant arsenic compound. This oxid, AsjOg + water 3H2O = 2H3ASO3. The salts are known as arsenites. H — 0\ Arsenic Acid, HjAsO,. H — O— ( As = O ). H — ()/ Usually prepared by oxidizing arsenous acid by ni- tric acid and evaporating the solution. The salts are known as arsenates. H — 0\ Orthophosphonc Acid, H3PO,. H — O— (P = O). H — 0/ Phosphoric acid ordinary is the most imjiortant acid of phosphorus. Prepared by boiling phos- phorus with dilute nitric acid and evaporating to a syrupy consistency. 3P2 + 10HNO3 + 4H,0 = 6H3PO, -f- 5xN,0.,. It is colorless, odorless, strongly acid liquid and con- tains 85% of absolute phosphoric acid. Is mi-cible with water and alcohol in all proportions. It has a specific gravity of 1.7 1 at 15° C. Heated to 200° C, it loses water and changes to pyrophosphoric acid, H2PO7. At still higher temperatures, it forms meta- phosphoric acid, HPO,- Dilute j)hosphoric acid TRTRABASIC ACIDS. 75 U. S. P. contains lo'y^ of acid, and iias a specific gravity of 1.057 '^^ 15° C. TETRABASIC ACIDS. (Those Having Power of Forming Four Classes of Salts or With Four Available Hydrogens.) H — •P = Pyro phosphoric A cid. H — () /P = U \ H — O \P = / Forms salts known as pyrophosphates; sodium pyro- phosphate, Na4P207. CHAPTER IX. METALS. Over fifty metals are included in the ordinary classification, but the number is being constantly increased by new discoveries, and older ones are fre- cjuently separated into simpler ones. Of these only twenty-seven are considered as common metals, the remainder being known as rare metals. This is not strictly true, but only those that are of pharmaceutic importance will be considered in detail, and these number only about twenty-five. The classification and order of study will be lliat commonly employed in qualitative analysis in order to teach both the general properties and the methods of separation at the same time. Classifications in relation to atomic weight and valence arc given on pages 78, 173, 178. There are certain characteristic properties pos- sessed by all metals: 1. Metallic luster, (juite distinctive. 2. (iood conductors of heat and electricity, and often used for such purposes. 3. All solids at ordinary temperature except mer- cury, which is the only liquid metal. 4. Nearly all electro-positive. 5. Color variable within limits of shades of white and gray, except copper and gold. 76 PROPERTIES OF METALS- 77 6. Weight, heavier than water, with the exception of lithium, potassium and sodium, which are lighter than water. 7. Malleability marked, gold being exceedingly malleable and sodium the least so. 8. Ductility, tenacity or cohesion, these varying from the greatest tenacity of silver and iron to lead, the least tenacious. 9. Fusibility, nonvolatility at ordinary temper- ature and insolubility in ordinary solvents (water, alcohol, ether). The metals occur in varying abundance in ores, rocks and soils throughout the earth's crust and often as pure metal in the so-called pockets and veins. The methods of extraction are variable and will be individually discussed. The following classification will be followed for the more common metals, and the rare metals will I)e discussed in a chapter by themselves. 78 PHARMACEUTIC CHEMISTRY. B^U^ O 1=1 i I ^- g E I o 'a^ ,^ S^-'tdZ o*^ e2; S-- « . ^ H! > ►S" g si SI 1:1 s^ HHe-z^t^H^^- •2o ocn rtffl rtS-2-° ° »-; M > o O E<5 8ooP Ib 2; '^ o ^ ?; 3 0. ^ S S SB .> N w o o B>: E2 B~ 2« Sir ^ o CHAPTER X. SILVER, LEAD AND MERCURY. The hydrochloric acid group, is so called on account of their precipitating from their solutions by the use of hydrochloric acid or soluble chlorids, forming insoluble chlorids with these metals. This group is also considered first because of the importance of the compounds and the fact that they are fewer in number and simpler in their composition. The metals included are mercury, Hg, which exists in this group in the univalent or monad state, lead, Pb, and silver, Ag. The salts or compounds of the dvad mercurv, will be discussed in Chapter XII. MERCURY, Hg. Hydrargyrum U. S. P. At. Wt., 198.5 (200). Sp. gr., 13.5. Valence, i and 2. Common name, quicksilver. Source. — Occurs in nature chiefly as cinnabar, HgS, mercuric sulfid; rarely, as globules of the metal enclosed in rocks. Obtained chiefly from Spain, but also in Peru, Mexico and Japan. Preparation. — From cinnabar by roasting, the sulfur uniting with oxygen to form gaseous sulfur dioxid and escaping while the mercury distills. Thus, HgS + O, = Hg + SO3. Properties. — A silver-white, lustrous metal, liquid at ordinary temperature, congealing at 38.8'^ 79 8o PHARMACEUTIC CHEMISTRY. boils at 360° and ver)- slightly volatile at ordinar)' temperature. It has the same atomic weight and vapor density, hence its molecule consists of one atom only. If pure, it is unchanged at ordinary tempera- ture, but above 300° it becomes coated with a film of mercuric oxid readily acted on by nitric acid but more difficultly by sulfuric and hydrochloric in the cold. Pure mercury poured on glass or paper does not adhere or form tails to the drops, but retains its spherical shape. It forms two series of compounds the mercurous and mercuric. The for merare less stable, contain a larger percentage of the metal, are less soluble and consequently less poisonous. Toxicology. — IMetallic mercury is not poisonous, but when it or its salts become soluble, their poison- ous nature is very pronounced. Children tolerate mercurials much better than adults. Treatment of poisoning should consist of albumen, as milk or eggs, and prompt emesis. Tests. — Mercurial compounds in solution arc read- ily detected by immersing a strip of bright copper foil in the solution in the presence of free hydro- chloric acid. A white-silvery film of copper amalgam quicklv forms. Solutions also give a black precipi- tate with hydrogen sulfid and a white precipitate with hydrochloric acid if in Ihc nu-rc urous state. Uses. — Mercury nictal is used in many amalgams, since it forms amalgam.; with nearl\ all metals. Tin amalgam is used for coating mirrors. The metal as such is largely u.sed for thermometers, barometers, thermostats and other instruments, and it enters MERCURY. 8 1 into five official preparations, viz.: Emplastrum hydrargyri, U. S. P., 309^ ; Massa hydrargyri, U. S. P., Zf/c; Hydrargyrum cum creta, U. S. P., 38%; Un- guentum hydrargyri, U. S. P., 50%, and Ung. hydrargyri dilutum, U. S. P., iz-^c- Compounds. — It may be remembered that all the official compounds of mercury are required to be 99^% pure, except hydrargyrum ammoniatum, which is 78%. The mercurous salts of the U. S. P. are but two in number — for instance, the chlorid, HgCl, and iodid, Hgl. Other salts of some importance, however, are the oxid, nitrate and sulfate. I. Merf«^o«5c///oric? (Hydrargyri chor'dum mile. U. S. P.), HgCl, calomel, mild chlorid of mercury, proto chlorid, subchlorid, submuriate of mercury, or, mercurius dulcis. A heavy, white, impalpable powder, insoluble, volatile, prepared usually by subliming mercury, mercury sulfate and sodium chlorid, and washing out the corrosive chlorid that also forms. Hg + HgSO, + 2NaCl = 2HgCl + Na^SO,. It may be also prepared by heating mercury with mercuric chlorid: Hg + HgCU = 2HgCl; by mixing solutions of mercurous nitrate and sodium chlorid: Hg (NO3) + NaCl = NaNOg + HgCl; also by a solution of mercurous nitrate and mercuric chlorid, Hg.CNO,)^ + HgCl3 = 2HgCl + Hg (NOg)^. It is used medicinally as a laxative and alterative. Yellow mercurous iodid (Hydrargyri iodidum tlavum U. S. P.), Hgl, protoiodid, yellow iodid, green iodid, hydrargyri iodidum, viride, U. S. P., '80. A 6 82 PHARMACEUTIC CHEMISTRY. yellowish-green, insoluble salt prepared by dissolv- ing mercury in dilute nitric acid to form mercurous nitrate and decomposing this with potassium iodid: (i) Hg2 + 2HNO3 = 2HgN03 + H2 (2) HgNOg -f KI = Hgl-f KNO,. Used as an alterative. Mercurous oxid, HgjO, protoxid, or black oxid, prepared by interaction of sodium hydrate and mer- curous nitrate. Hg2(N03)2 + aNaOH = HgjO -f- 2NaN03 + HjO. A brownish-black, heavy, taste- less, insoluble powder; unstable, sunlight converting it into mercuric oxid and mercury. It is the essential ingredient of lotio nigra, or black wash of the N. F., made by adding calomel to lime-water, 2HgCl -|- Ca(t)H)2 = Hg^O -f CaClj + H^O. Mercurous nitrate, HgNOg, white or colorless, prismatic and very unstable, efflorescent, crystals prepared by action of dilute nitric acid on mercury. 6Hg + 8HNO3 = sUg, (NO,), + N2O2 + 4H26. Mercurous sulfate, HgjSO^, a white, crystalline salt, easily decomposed to the basic salt, prepared by action of sulfuric acid on an excess of mercury, is of very little value. For discussion of mercuric com- j)ounds, see Chapter XII. LEAD, Plumbum, Pb, 205. Sp. gr., 11.4. Melt- ing point, 325°. Sometimes found free, but com- mercially in abundant ores chiefly as sulfid, galena, PbS, and as carbonate, cerusite, PbCOg. The ores usually contain some silver, which is removed by crystallizing and cupelling. The lead is obtained by continued roasting of the ores. LEAD. 83 Properties. — A soft metal, bluish-white, brilliant silvery luster on fresh surfaces, but quickly tarnished. It is malleable and pliable, but not ductile or tena- cious. Conducts heat well, electricity poorly, melts at 325° and volatilizes at a white heat. It is pre- cipitated from its solutions by zinc, tin and iron, acted upon slowly by most acids, but freely by nitric acid. In presence of air, water dissolves lead by forming the hydroxid. Nitrates and nitrites in- crease, and carbonates, chlorids and sulfates decrease this solubility. These facts are important because potable waters are so commonly conducted through lead pipes. Uses. — The commercial uses of the metal are well known. It also forms a number of useful alloys: with tin it forms solder, fusible at 186°; with zinc it forms Babbitt metal, and with antimony forms type- metal and is an ingredient of types of glass known as flint glass. The greatest consumption of lead, outside of its mechanical uses in pipes, sheetings, etc., is probably as a paint pigment in the form of basic lead carbonate, or white lead, 2PbC03 PbCOH)^, even yet largely manufactured by the old Dutch method, dependent upon the corrosion of the lead by acetic acid in the presence of carbon dioxid and moist air. Other methods have been devised, but the Dutch method seems to give the greatest satisfaction. Toxicology. — All soluble lead compounds and those that are rendered soluble in digestive fluids or other- wise in the animal economy are quite poisonous. 84 PHARMACEUTIC CHEMISTRY. The chronic form of poisoning, known as painters' colic, is very common, due to contact with the com- pounds of lead in painting, etc. The acute conditions of poisoning are quite rare and seldom fatal and usually produced by a large single dose of such salts as acetate or carbonate. When such a case occurs, magnesium sulfate should be at once administered, as it produces an insoluble sulfate with the lead. Emesis should be induced. Compounds. — lead acetate, (PlumbiacetasU.S.P.), Pb (€211302)2 + 3H,0. sugar of lead, sal saturni, colorless, shining, transparent, prisms or plates, heavy crystalline masses or granules, with a faint acetous odor, sweetish, astringent, metallic taste; efflorescent; absorbs carbon dioxid from the air. Soluble in two parts of water. Incompatible with very many substances, such as alkali salts, organic salts and soluble chlorids and sulfates. May be made by dissolving lead oxid in acetic acid and crys- tallizing. PbO + 2C,H,02 = Pb(C2H302)2 + H2O. Used medicinally as an external astringent. Enters into emplastrum plumbi, ung. diachylon, 50*7^; liq. plumbi subacetate, 25%; liq. plumbi subacetatis dilutus, 1%, and ceratum plumbi subacetatis — 20%. Lead iodid, Plumli iodidum, Pbl,, precipitated from lead solutions by potassium iodid. Should be preserved in well-stoppered bottles away from light. A heavy, bright-yellow powder, odorless, tasteless and slightly soluble in water. (1-1300) 99% pure. Used medicinally as a sorbefacient. The ointment of lead iodid, ro'',', was formerly official. SllA'KK. 85 Lead nitrate (Plumbi nitras), Pb(N03)2, 99.5% pure. Prepared by dissolving lead or its oxids in excess of nitric acid. PbO + 2HNO3 = Pb(N03)2 + H2O. Colorless, octahedral crystals, sometimes transparent, often nearly opaque. Odorless, sweet- ish, astringent, metallic taste. Soluble in less than two parts of water. It is used as a caustic applied as a powder; its solution is used as a disinfectant. Lead oxld (Plumbi oxidum), PbO, 96% pure, (litharge). Prepared by heating metallic lead, its carbonate or nitrate with access of air, obtained largely as a by-product in silver extraction. A heavy, yellow or reddish -yellow powder, odorless and taste- less. Insoluble in ordinary solvents, readily so in acetic and nitric acids. Used in the preparation of various lead salts, solution of lead subacetate and formerly in preparing lead plaster. Other oxids of lead: dioxid, PbOj, plumboso-plumbic oxid, or red lead, PbgO^, and plumbic suboxid, PbjO. None are of much importance. Lead chromate, PbCrO^, "chrome yellow," is much used as a pigment. Lead sulfid and lead carbonate have been mentioned. SILVER, Ag., Argenium, 108. Valence, i. Occurrence. — Occurs native to a small extent, but principally as ores in combination with chlorin, bromin, sulfur, etc. Associated with lead, copper, gold, etc. Found principally in western United States, Mexico, Hungary and Saxony. Preparation. — The ore is roasted with sodium chlorid forming silver chlorid, and this is decom- posed by iron scraps. Metallic mercury is added. 86 PHARMACEUTIC CHEMISTRY. forms an amalgam with the silver, and the mercury is distilled from it. Different ores require individual treatment, however, and works on metallurgy should be consulted for full details of extraction. Properties. — It is a white, lustrous metal, perma- nent in the air, very malleable, tenacious, and ductile. An excellent conductor of heat and electricity, feebly attacked by most acids, but freely by nitric acid. Specific gravity, 10.5; melting-point, 1040°. Uses. — Seldom used by itself, on account of its softness, but usually combined with copper to harden it. Used much in art work, cutlery and as a coin medium, ornaments, etc. Coin silver contains 10% copper in the coins of the United States, France, Germany and Austria. British coin silver contains 7.5% copper. In pharmacy and medicine silver is used for surgical instrument ])lating and in the preparation of silver salts. Compounds. — Silver cyanid (Argenti cyanidum U. S. P.), AgCn; purity, 99.5%, equivalent to 80.5% metallic silver. Prepared by passing hydrocyanic acid through solution of silver nitrate or adding a soluble cyanid to the same. Properties. — A white, permanent powder, odorless and tasteless. Insoluble in ordinary solvents, but soluble in ammonia water and potassium cyanid solution. In solution with the latter it is used in electro-plating. Used for the extemporaneous prep- aration of dilute hydrocyanic acid, 2% Silver nitrate (Argenti nitras U. S. P.), AgNOj) purity, 99.9%. Should be kept protected from light. SILVER SALTS. 87 Preparation. — Made by dissolving silver in diluted nitric acid. Properties. — Colorless, transparent, tabular rhom- bic crystals reduced to grayish-black by light or organic matter. Odorless with a strongly metallic and caustic taste. Soluble in 0.54 parts of water, 24 parts of alcohol. Incompatible with alkalies, most acids and organic matter. Melts at about 200° to a faintly yellow liquid. When so fused and cooled in moulds, it forms the oflticial argenti nitras fusus U.S. P., known as lunar caustic and "lapis in- fernalis." When one part silver nitrate and two parts potassium nitrate are fused together and moulded, it is called argenti nitras dilutus U. S. P., or mitigated caustic. The salt is useful as an anti- septic, astringent and caustic. It also finds use in photography, in the manufacture of hair dyes, indeli- ble inks and in silvering mirrors, etc. It is poisonous, sodium chlorid being the best antidote. Silver stains on the skin may be removed by solution of potassium cyanid, sodium thiosulfate or ammonia water. Silver oxid (Argenti oxidum), AgjO; purity, 99.8%; equivalent to 92.9% silver. Easily reduced by light organic matter and ammonia. Properties. — A heavy, dark-brownish to black powder, odorless, with metallic taste. Slightly soluble in water. Decomposed at 300°. Feebly astringent. The chlorid, bromid and iodid of silver are very similar, insoluble, easily reduced and find their 88 I'llAKMACELTIC CHEMISTRY greatest use in photography, which depends upon the ready reduction of these salts when exposed to light. Toxicology. — Poisoning by silver salts is quite rare, sodium chlorid or other soluble chlorids being the antidotes. CHAPTER XL ARSENIC, ANTIMONY, TIN. This group is, as a whole, known as the hydrogen sulfid group, because the metals included in the group will be precipitated from acid solution by the general group reagent, hydrogen sulfid, HjS. After separating the metals of Group I by hydrochloric acid, the residual solution is treated with a current of hydrogen sulfid gas. The metals are precipitated as sulfids. We further divide this group into two divisions. Those metallic sulfids 'previously formed that are soluble in ammonium sulfid, viz.: arsenic, antimony and tin; and those insoluble in ammonium sulfid, viz.: bismuth, copper, cadmium, mercuric mercury and lead. Tlie former group is the sub- ject of this chapter. The medicinal uses of these metals are but few and very few of the salts are offi- cial. Arsenic is the most valuable of the three, medicinally. ARS2NIC, Arsenum, As, 74.4. Mol. wt., 299. Sp. gr., 5.7. Arsenic is found free in nature, but usually combined with sulfur or oxygen. Its principal ores are orpiment, AsjSg, realgar, AS2S2, and iron arseno-sulfid, FeAsS, also called " mispickel " or arsenical pyrites. It is widely scattered, though in minute quantities, throughout inorganic and many organic compounds. It is commonly present in 90 PHARMACEUTIC CHEMISTRY. iron jnrites and through this channel finds its way as an impurity into sulfuric acid, which is ])rc])ared from pyrites. Preparation. — Arsenic is prepared from pyrites by roasting to volatilize the arsenic which afterwards is purified by distillation. Properties. — Arsenic in many ways resembles a true metal, but it also has the properties of a non- metal, and since it possesses both the properties, it is often styled a metalloid (metal-like) element. It oc- curs both as amorphous substance and in irregular rhombohedral crystals. It volatilizes above ioo° C. and at i8o° C. is vaporized rapidly without melting. When so heated in presence of air, it unites with oxygen, producing grayish fumes which possess a garlicky odor. It burns with a bluish flame, which results in the production of an oxid. This oxid, chemically a trioxid, has the formula of AsjOj. Arsenic finds uses in the "hardening of shot, in pyrotechny, in the manufacture of paint pigments and is alloyed with iron and copper to increase their degree of brilliancy when polished. It is also used to produce many of the vermin poisons in agriculture. Compounds. — Arsenic forms two classes of com- pounds, the "ic" and the "ous." In the "ous" condition, it acts as a trivalent. In the "ic" as a pentavalent. Arsenic oxid, As-^Oj, when dissolved in water forms arsenic acid, which has the formula H3ASO4, and which forms salts called arsenates. The arsenic oxid is less poisonous than the arsenous oxid. This latter oxid, ofiicial in the U. S. P. under ARSENIC. 91 the title of arseni-trioxidum, AsjOg, commonly called arsenic, white arsenic, arsenic trioxid or ratsbane, is a white, gritty, crystalline powder, which, fused in sealed glass tubes, produces a vitreous mass grad- ually becoming opaque. It is slightly soluble in water, producing arsenous acid, HjAsOg, which forms unstable salts known as arsenites. The official article should be not less than 99.8% pure. The glassy variety changes by exposure to moist air to the opacjue variety which is more readily soluble. Medicinally, arsenic is used as a caustic, tonic and alterative, thought to be specific in various skin dis- eases. It enters into the solution of arsenous acid (liquor acidi arsenosi, 1%), the Donovan solution (liquor arseni et hydrargyri iodidi, 1% each), into the solution of sodium arsenate (liquor sodii arsenatis, 1%), and into the Fowler's solution (liquor potassii arsenitis, 1%). Of the chemical compounds of arsenic official we find the iodid (arseni iodidum), Aslg, which represents 16.3% of metallic arsenic and 82.7% of iodin. It is made by the direct union of the elements. It occurs in orange-red, crystalline odor- less powder, soluble, but partly decomposed in 12 parts of water, readily soluble in ether and chloro- form. It should be protected from heat and light.. The iodid is incompatible with most metallic salts, except the alkali metals. It is easily reduced or oxidized. Medicinally, the salt is used as an altera- tive. Arsenic forms similar compounds with the other halogen elements. Three sulfids of arsenic are known: arsenous sulfid, AsjS,, the disulfid. 92 PHARMACEl'TIC CHEMISTRY. AS2S2, and the pentasulfid, AsjSj. Cupric arsenite Cu3(As()3)2, is called Scheele's green. Paris green, or Schweinfurt's green, is a variable mi.xture of copper, acetate and arsenite, usually supposed to be cupric aceto-arsenite, made by boiling arsenous oxid in a solution of copper acetate and the formula Cu(C2H302)2, 3Cu(As02)2) has been ascribed to it. Both the greens are used as pigments in wall paper printing and the detached particles therefrom have frequently produced symptoms of chronic arsenical poisoning. The detection of arsenic in wall paper is frequently called for and the pharmacists should be ready to perform the same. Toxicology. — Arsenic is an important poison and from the time of its discovery has been used for crimi- nal purposes. All soluble compounds of arsenic are poisonous, the poison usually enters the system by the mouth, but it may be absorbed by the skin, mem- branes or by breathing. It permeates the entire body, but deposits more specifically in the liver. It is excreted both by the feces and by urine. In case of poisoning with arsenic, the stomach-tube is the first indication, emetics should be ])romptly administered. The chemical antidote is the ferric hydroxid or better the official ferric hydroxid with magnesia (ferri hydroxidum cum magnesii oxido), commonly known as the "arsenic antidote." This antidote is most admirable in its action: thus, the magnesium oxid which it contains neutralizes the acid of the gastric contents, producing neutral salt and thus preventing the solution of arsenic therein. MARSH TEST. 93 Dialysed iron is another form of iron found very effective, in both cases the iron combining with the arsenic and forming an insoluble ferric arsenate. Tests. — Numerous tests for the detection of arsenic are available, but no single test should be regarded as conclusive. Marsh's test is possibly the most im- portant, though in presence of organic matter it is not positive. This is conducted as follows: introduce into a flask some arsenic-free zinc (U. S. P. reagent) cover it with dilute sulfuric acid, close the flask with a stopper, perforated and supplied with a safety tube and provided with another tube turned at right angles horizontally drawn out to a fine point. The metallic zinc decomposes the acid and generates hydrogen, which in turn should be allowed at least fifteen minutes to drive out all the air from the con- tainer. The arsenical solution should next be in- troduced through the safety tube, the gas at the open end of the tube should next be lighted and a piece of cold porcelain dish (a porcelain crucible lid will do) held against the flame; if no black stain appears, arsenic and anti mony are not present. If a brownish- black spot is deposited, which when treated with a few drops of a solution of a hypochlorite dissolves, it indicates arsenic. If it does not dissolve, antimony is indicated. This test depends on the formation of arsin gas, ASH3, the product of the action of nas- cent hydrogen on arsenic in acid solutions. Fleitmann's test depends on dropping a few pieces of metallic zinc or aluminum in a solution of potas- sium hvdroxid, which contains a small quantity of 94 I'liARMAciamc chemistry. the arsenical solution. The test-tube is covered with a piece of filter paper which has previously been moist- ened with a solution of AgNOg. The arsin gas which is evolved acts upon the silver nitrate reducing it to metallic silver which produces a dark stain upon the paper. This test is important and valuable in that it differentiates arsenic from antimony (stibin not being evolved). Guttzeit^s test depends upon the reduction of lei d acetate by arsin, and Reinsch's test depends upon the reducing powers of copper on arsenical com- pounds. ANTIMONY, Stibium, Sb, 119.3. Sp. gr., 6.7. Melting-point, 450 C. Occurrence. — Antimony occurs native, scattered widely, but only in minute particles. It is found in combination as an oxid, SbjOg, commonly known as "antimony bloom" or white antimony, and as antimony ochre, AsSb^O^. In combination with sulfur, it occurs as stibnite, SbjSg, which is its most important ore and commercial source. It is also found combined with iron, copper, lead and other sulfids. Preparation. — Antinn)ny is obtained from the sulfids by heating with scrap iron in carbon crucibles or by roasting the ore with half its weight of charcoal. The two methods of extracting the metal from the ores will best be seen by the following two equations: (i) Sb^Sg + 3Fe = Sb2 + 3FeS. (2) SbjO, + 2C2 = 4CO + Sb... Properties. — Antimony is a bright, silver white, ANTIMONY COMPOUNDS. 95 br'ttle metal of crystalline structure, permanent at ordinary temperature, but at high heat it burns with a brilliant flame forming the trioxid, Sb-^Og. In cooling after liquefaction it expands, and this property makes it very valuable as an alloy. Its principal alloys are: type-metal (antimony, lead and tin) and britannia metal (antimony, copper and tin). Antimony is a poor conductor of heat and electricity. When acted upon by concentrated sul- furic or hydrochloric acid, it forms salts; by nitric acid, it is oxidized, forming oxids. Compounds. — Antimony forms both "ic" and "ous" compounds, nearly all of which are decom- posed by water. Tartar emetic (antimonii et potas- sii- tartras) is the only ofl&cial salt of antimony. It has the formula 2K(SbO)C,H,06 + H2O and is prepared by boiling antimonous oxid, SbjOg, with potassium bitartrate, filtering and evaporating the solution. Reaction: SbaOg + 2KHC4H^Og = 2K(SbO)C4H40e-|-H20. Potassium antimonyl tar- trate (its chemical name) is a white crystalline salt, soluble in hot water, slowly in cold water; used as an emetic and expectorant, it enters into the com- pound syrup of squills (syrupus scillae compositus, 0.4%). Antimony forms salts much the same as described under arsenic: Stibin, SbHg; several halo- gen salts, among which the trichlorid, SbClg, commonly know^n as "butter of antimony," finds much use in the arts and manufactures. It forms three oxids, Sb,©,, Sb204 and SboOj. It also forms two sultids, Sb20^ and ^h^^^^, and a number 96 PIJARMACKUTIC CHEMISTRY. of less important salts. In the U. S. P. (8th Rev.) antimony sulfid, purified antimony sulfid, antimony oxid, all of use in the preparation of other antimony compounds, but rarely used alone, have been dis- missed. The tests described under arsenic, especially Marsh's and Fleitmann's test, of which the latter is valuable in that it differentiates the antimony from the arsenic, are valuable. TIN. — Slannum, Sn, 117. Sp. gr., 7.3. Occurrence. — Tin does not occur native, but al- most entirely as oxid. Tin-stone, SbOj, commonly known as cassiterite, is its principal ore. When found in veins of rock, it is called mine-tin and when occurring in water beds, it is known as stream tin. It is sometimes found associated with other metals as a sulfid. Its principal mines are in Cornwall and England. In America it is found in California, South Dakota and New Hampshire. Preparalio)!. — The jjroccss of extracting tin from its ores ordinarily consists in three steps: (1) calcin- ing; (2) washing; (3) reducing or smelting. The impure metal is cast into ingots which, when sub- jected to regulated heat, allow the tin to melt and run off, leaving behind the iron and copper. Properties. — A .soft, white metal, harder than lead, not acted upon bv water or air at ordinary tempera- tures. Malleable, forming tin-foil, and, at tempera- tures just below melting, brittle. At high tempera- tures it burns, forming an oxid. It alloys with other metals, forming many useful ones, such as l)ewter, solder, l)rasses, ])ronzes, britannia and type- TIN. 97 metals, fusible alloys with l)ismuth, etc. It is used as a protective of iron and other metals, by covering them with a thin layer of tin. Tinware usually is made of sheet iron covered with tin. Its salts are used as mordants in dyeing and cloth printing. It forms two classes of compounds, the "ous" and the "ic," the first being divalent, the second tet- ravalent. It forms oxids — stannous oxid (SnO) and stannic oxid (SnOj) — the former black and the latter white. These oxids form two acids with water — stannic acid (H2Sn02), and metastannic acid (Hi(,SngO,g). The latter is also produced by acting with concentrated nitric acid on metallic tin. No salts of tin are official, and find no application in medicine. The salts are poisonous, but rarely used as poisons. Accidental cases of poisoning do occur in dye works, etc., in which cases emetics and demul- cent drinks, like milk, should be administered freely. Tests. — Tin may be detected by precipitating it from solution by hydrogen sulfid, converting it into oxid with nitric acid and weighing as such, if the quantity is desired. CHAPTER XII. HYDROGEN SULFID GROUP (Second Division). BISMUTH, COPPER, CADMIUM AND MERCURY ("IC"). This is somewhat similar to the group just de- scribed. The metals to be discussed are precipi- tated by hydrogen sulfid, but members of this group are insoluble in ammonium sulfid solution, hence they are grouped together. BISMUTH.— Bismulhum, Bi, 207. Sp. gr., 9.9. Bismuth differs from the other metals previously con- sidered in that it occurs most commonly in the un- combined state. However, it is also found as an oxid (BijOg), as bismuth ochre, and as sulfid (Bi._,S.,) in bismuth glance. Its principal minesare in Saxony, where the metal is found associated with silver, co- balt and nickel. Preparation. — The ores are heated in inclined iron pipes, and the melted bismuth run off from the other material. Subsecjuent purification is necessary. Properties. — It is a white, lustrous metal with a reddish tint, very brittle, fusible at 268^ Centigrade, volatile at higher temperatures, and at very high heat it burns, forming the trioxiil Bi.O.,. it is unaft'ected by dry air at ordinary tcmi)crature, t)Ut is tarnished in moist air. It is attacked only slightly 98 BISMUTH COMPOUNDS. 99 by hydrochloric acid, but more readily by sulfuric and nitric acids. It is a poor conductor of electricity and it expands on cooling after fusion. If slowly cooled, obtuse rhombohedral crystals may be ob- tained. The metal is but little used except in alloys, to which it imparts ease of fusion and at the same time hardness. It plays the part of both a metal and a nonmetal under differing conditions. Its com- pounds are much used in medicine. It forms both "ous" and "ic" compounds, having the valence of 3 and 4, respectively. Most neutral salts of bis- muth are converted into basic salts by water, and these latter are mostly used in medicine. Bismuth Citrate (Bismuthi Ci ras U.S. P.) — BiCgHsO^, should contain not less than 58% nor more than 60% of pure bismuth oxid. It is pre- pared by the action of the subnitrate on a solution of citric acid: (BiONOs -f HjO) + {Yl^C^Yi^O^ + H2O) = BiCgHjO^ + HNO3 + 3H2O. It is a white, amorphous or crystalline powder, odorless, tasteless, insoluble in water, but soluble in ammonia water. It is used as the base of soluble bismuth and ammonium citrate — bismuthi et ammonii citras U. S. P. It is astringent and antiseptic. Bismuth and Ammonium Citrate (Bismuthi et Ammonii Citras U. S. P.) — Similar in uses to the citrate. It is a scale salt prepared by dissolving the citrate in dilute ammonia water and subsequent scaling. Bismuth Subcarbonate (Bismuthi Subcarbonas lOO I'llARMACEUTIC CHEMISTRY. U.S. P.) — Comp().'^ition is variable. Purity, 90^^. It is a white or pale yellow, odorless, tasteless and insoluble powder, decomposed by mineral acids. It is prepared from the su!)nitrate and an alkali carbonate: 2Bi(N03)3 + sNa^COj + H,0 = (BiO).,C03 + H2O + 6NaN03 + 2CO2. Bismuth Subgalate (Bismuthi Subga'asU.S.P.) — Has a variable composition. It should contain from 52% to 57% bismuth oxid. It is an amorphous, bright-yellow, odorless, tasteless, insoluble powder, decomposed by strong acids. It may be prepared l)y mixing a warm solution of gallic acid with bis- muth nitrate and glacial acetic acid; the substance is also designated "dermatol." Bismuth Subnitrate (Bismuthi Subnitras U.S. P.) — BiONC).,. .Also called "magisterium " and basic bismuth nitrate. It should yield So^^p of bismuth oxid, and is of varying composition. Description: It is a white, odorless, insoluble, almost tasteless powder, soluble in mineral acids, incom])atible with alkaline carbonates, iodids, chlorids, tannatcs, etc. It is prepared by dissolving the metal in nitric acid and pouring the nitrate into a large (|uantity of water, whereby the sul)nitrate is ])re(ipilated. Thus: (i) 2Bi + 8HNO3 = 2Bi(N03)., + 2N() + 4H,0. (2) Bi(N03),, + H,0 = BiON03 -f 2HNO3. Other reactions, depending on the quantity of water that enters the reaction, may be given. Bismuth Subsalicylate (Bismullu Subsalicylas U.S.P.)— Bi(C7H303)3Bi203. Basic bismuth salicy- late should contain from 62% to 64% of bismuth oxid. It is a white, odorless, tasteless, permanent, insoluble powder, partly soluble in and decomposed by nitric and hydrochloric acids. It is prepared by precipi- tating bismuth nitrate with alkah, boiling, adding sali- cylic acid to the oxid so obtained, and heating to evaporation, washing and drying. Other valuable . medicinal salts are the benzoate, oleate, tribromate, phenolate and many others of similar kind. Bismuth forms four oxids — bismuth dioxid, Bi^Oj; bismuth trioxid, 61,03; bismuth tetroxid, 6120^; and bismuth pentoxid, Bi^O^. It also forms a hydroxid, but does not form a trihydrid. Most bismuth salts are tonic, astringent and antifermentative. They are largely employed in intestinal disorders. Poison- ous symptoms observed after using bismuth salts are nearly always due to arsenical impurity. Tests. — Neutral and acid solutions of the salt are precipitated by water. With sulfids it gives a black precipitate, alkali hydroxids give a white precipitate ; iodids give a brown precipitate. Potassium sulpho- cyanate paper moistened with a bismuth solution turns yellow on drying. COPPER.— Cuprum, Cu., 63.2. Sp. gr., 8.9 Occurrence. — It is found native in large quantities, notably in the Lake Superior region and in China, Japan and Sweden. In combination, it is exceedingly abundant and is found in many forms, chiefly as sulfid, chalcocite, pyrites, carbonate (malachite) and cu- prite or oxid. Numerous methods of separating it 102 PHARMACEUTIC CHEMISTRY. from its ores arc employed, all depending upon the nature of the ore. Properties. — It is a reddish-brown metal, lustrous, very tenacious and ductile, being readily drawn into fine wire. It is also very malleable, producing very thin leaves. It is fusible and volatile at very high temperatures producing an emerald-green vapor. It .is readily attacked by nitric acid, slowly by hydro- chloric and sulfuric acids in the air, also very slowly by air itself, forming a green, basic carbonate. Cop- per is second only to silver as a conductor of electri- city, and is extensively used for all electrical pur- poses. It is also used in electrotyping and very largely in the form of alloys, the most important of which are those with zinc (brass and Muntz metal), with tin (gun metal, bronze and speculum metal), with aluminum (aluminum bronze) and with silver and gold, the respective coin metals. Compounds. — Copper forms both "ous" and "ic" compounds. The cuprous oxid is the only impor- tant "ous" salt which occurs native, as red copper ore, CujO. It is produced by the reduction of cupric chlorid (CuClj), and also in the alkaline copper solution (Fehling's solution) with grape sugar. It is insoluble in water, easily affected by acids and fuses at red heat. Copper forms chlorid, hydroxid, oxid, nitrate, sulfate, carbonate and sultid, the only one retognized officially being the sulfate. Cupric Sulfate (cupri su fas U. S. P.), Cu SO,. 5H2O. — Copper sulfate, blue \itriol, blue stone; purit}-, not less than g9.5'( . COPPER COMPOUNDS. I03 Description. — Transparent, large deep-blue crys- tals, efflorescent, odorless with metallic, astringent taste. Soluble in 2.2 parts of water, 3.5 parts of glycerin; insoluble in alcohol. Incompatible with fixed alkali hydroxids. Preparation. — (i) By dissolving cupric oxid in dilute sulfuric acid, filtering, evaporating and crystal- lizing: CuO + H.SO, = CuSO, + H2O. (2) By the action of hot, concentrated sulfuric acid on metallic copper: Cu + 2H2SO, = CuSO, + SO2 + 2H3O. (3) By roasting copper pyrite in the air, in which process the sulfate is formed in conjunction with the sulfate of iron. It is used as a caustic, astringent and emetic. A solution of cupric sulfate in which some ammonium chlorid has been dissolved, upon the addition of sodium hydroxid, forms cupric hydroxid. This dissolved in ammonia water forms Schweizer's reagent which dissolves cotton wool and other forms of cellulose, which can be reprecipitated from the solution by the addition of salts or acids. The commercial compounds and pigments of copper are very important. Among these the follow- ing may be named: ^^ Paris Green, chemically cupric acetoarsenite (Cu(C2H302)2, 3CuO^As2); Verdigris, chemically copper subacetate, copper oxyacetate, basic acetate of copper (Cu (0211302)2, 2CuO -I-3H2O). Copper subacetate is prepared by exposing copper to the action of acetic acid and air, and recently the term verdigris was incorrectly applied to the I04 PIlARMACEl'TIC CHEMISTRY. green carbonates which form on the surface of copper salts. Scheele's Green is the copper arsenite of com- merce, a very valuable, though very poisonous pig- ment, employed in wall-paper printing, in book covers, etc. It is prepared by mixing solutions of copper sulfate and sodium arsenite, washing the bright-green precipitate obtained, and drying. Brunswick Green is a mixture of copper carbonate and chalk. Brigh- ton Green is copper acetate mixed with chalk. Mountain Green is the native copper carbonate. Neiiwieder Green, is a mixture of Schweinfurt green with gypsum and barium sulfates. Green vcrdites is the basic carbonate and oxid mixed with chalk. Toxicology. — Copper salts are probably falsely credited with very poisonous properties, fOr such are likely due to arsenical contamination, or to the double salts of copper and arsenic. Albuminous drinks and emetics are indicated in cases of copper poisoning. Tests.— \mmon\ix. water produces a light-blue precipitate, changing to deep blue solution with excess. Hydrogen sultid produces a black precipi- tate (CuS). Potassium cyanid produces a w^hite precipitate. Minute quantities may be detected by taking up with dilute nitric acid, neutralizing with ammonia, again acidifying with acetic acid, and adding potassium ferricyanid. A red color indi- cates copper. Copper salts color Bunsen flame green, excepting the chlorid which colors it blue. CADMIUM- C\l, 112. Sp. gr., S.6. Cadmium never occurs unct)nil)incd and is found in but few ores, most often accomi)anying zinc, from which it is obtained by distilling, it being more volatile than the latter. Description. — It is a bluish-white metal similar to zinc, but more malleable and ductile. It melts at 320° C. Heated, it burns, forming brown oxid. Compounds. — No compounds of cadmium are used in pharmacy. Its alloys are valuable commer- cially. The element is a dyad, forming hydroxid, oxid, chlorid, iodid, sulfate and sulfid. Cadmium oxid (CdO) is a brown salt; the sulfid (CdS) is a bright-yellow pigment valued as a paint. The iodid and bromid have l^een used in photography. MERCURIC— MERCURY.— Mercury has been fully discussed in Chapter X (see page 79), and only the mercuric compounds that occur in this grouping need here be discussed. The mercuric compounds are more numerous and important. Mercury plays here the part of a dyad or divalent element, and mercuric compounds are always pro- duced when the metal is dissolved in an excess of the acid. Mercuric chlorid is an important salt of mercury (hydrargyri chloridum corrosivum, U. S.P.), HgClg, also called bichlorid, perchlorid, muriate and corrosive sublimate. • Preparation. — By subliming a dry mixture ol mercuric sulfate and sodium chlorid. HgSO^-l- 2NaCl = HgCl, -f NajSOj. The sublimed form is that of rectangular octahedra; while that crystallized from a solution assumes rhombic prism form. It is, therefore, dimorphous. It is soluble in 16 parts of water, 14 parts of glycerin, 3 of alcohol. In presence Io6 PHARMACEUTIC CITE \r 1ST RV of heavy metals it is reduced to the mercurous state (calomel). Its aqueous solution, treated with an alkaline hydroxid (lime water), produces a yellow- precipitate of mercuric oxid (HgO),the liquid so produced being known as "yellow wash" (lotio flava, N. F., or "aqua phagedenica tlava " of the ancients). Yellow mercuric oxid (hvdrargyri oxidum flavum U. S. P.) is })repared by precipitating mercuric chlorid solution with sodium hydroxid. Reaction: HgCls + 2NaOH = HgO + 2NaCl + H2O. An orange-yellow, amorphous, insoluble powder, soluble in dilute acids. It is more active than the red oxid and therefore preferred in skin prepara- tions and eye salves. Ammoniated mercury (hydrar- gyrum ammoniatum U. S. P.), NH.HgCM, white precipitate, ammoniated chlorid of mercury, amido- chlorid of mercury, is produced by mixing solutions of mercuric chlorid and ammonia water, washing the precipitate with water containing a little am- monia and drying. Reaction: 2NH,OH + HgCU = NH.HgCl + NH.Cl + 2W^O. It is an insoluble, white powder, soluble in warm hydrochloric or nitric acids. Red mercuric iodid (hydrargyri iodidum rubrum U.S. P.), Hgl., red iodid, biniodid, deutoiodid. mercuric iodid. Preparation. — Made by mixing solutions of mer- curic chlorid and potassium iodid, washing free from chlorids and drying the precipitate. Reaction: HgCU + 2KI = Hgl,, + 2KCI. It is a scarlet-red ])owder, usually amor|)hous, MERCURIC OXID. 107 sometimes found in octahedral and rhombic needles, hence is dimorphous. It dissolves in a solution of potassium iodid or mercuric chlorid. It is nearly insoluble in all other solvents. It is an ingredient of Donovan's solution (liquor arseni et hydrargyri iodidi U. S. P.). Red mercuric ox id (hydrargyri oxidum rubrum U. S. P.), HgO, red precipitate, peroxid. Preparation. — By heating nitrate of mercury crystals till nitrous fumes cease to evolve. It is a red powder or crystalline scale. By dissolving it in hydrochloric acid and evaporating, the mercuric chlorid is obtained. The difference in the two oxids — yellow and red — lies in the methods of their preparation, the former made by precipitation, the latter by ignition of the nitrate. Students should remember that there is one each official — a mer- cnrous and a mercuric chlorid and iodid — but that both the oxids have the same composition, both being mercuric salts. They are both insoluble in ordinary solvents, but soluble in dilute acids. Among the unofficial mercuric compounds are the cyanid (HgCNj) a very poisonous, opaque-white mass, soluble in 12 parts of water; turpeth mineral (hydrargyri subsulfas flavus), Hg(HgO)S04, basic sulfate of mercury, a lemon-yellow powder used as an emetic; mercuric nitrate Hg(N03)2, pre- pared by careful solution of mercury or of the oxid in nitric acid. It is used as a reagent in "Liebig's urea test" and for preparing other compounds of mercurv. CHAPTER XIII. IRON, ALUMINUM, CHROMIUM. The amuwnium siilfid group embraces those metals which are precipitated by ammonium sulfid solution. The entire group is subdivided into two divisions: iron, aluminum and chromium com- prise the first division, and cobalt, nickel, man- ganese and zinc make up the second division. The reason for this division is that while ammonium sul- fid precipitates all the seven metals, it does not form the same compounds with all. Thus, the metals of the first division are precipitated as hydroxids, while those of the second division are precipitated as sul- fids. Moreover, the first division may be precipi- tated by ammonium hydroxid in the presence of am- monium chlorid, which latter i)revents the precipita- tion of the remaining metals. Thus, the first three metals are separated from the second division as hydroxids. If ammonium sulfid is now added to the entire division, it changes the iron hydroxid to a sulfid, but does not affect the remaining two. IRON. — Ferrum, Fe, 56. Sp. gr., 7.1 to 8.1. Occurrence. — Iron is found native in small quan- tities in the meteorites, in some to the extent of 98%. It is a metal of great importance and is widely dis- tributed. The ores that contain iron in combination are numerous, but only few of the more important 108 IRON. 109 ones will be here mentioned. Magnetite, Fefi^ consists of ferroso-ferric oxid = FeO, Fe203; He- matite, chiefly ferric oxid, FcjOg; Limonite (or brown hematite), a variable mixture of the oxid and hy- droxid, and Siderite (spathic iron), consists of ferrous carbonate, FeCOg. The sulfur ores, as, for example, the iron pyrites (FeS^,), are not well adapted to ex- traction, but are valuable for the manufacture of the acids of sulfur. Preparation. — Iron exists in three forms — as cast iron, wrought or malleable iron and steel. To understand the relationship existing between these it is best to study the processes of their manufacture. The ore in case of the hematites is first calcined to remove the water, and in case of the carbonate ores, the carbon dioxid. The calcined ore consists chiefly of ferric oxid and it is smelted in blast furnaces with limestone and coke. Limestone forms a fusible slag with the silica present while the coke burns in the hot air introduced by the blast tubes, forming carbon monoxid, which serves as a reducing agent of the glowing ferric oxid to metallic iron. Reaction: Fe^Oj + 3CO = Fe, + 3CO2. The smelting is continued uninterruptedly, the fur- nace being supplied with fresh material so that molten iron is continuously formed at the bottom of the furnace from which it is drawn off from time to time at a special tap-hole which is temporarily blocked up with clay, while.the slag of calcium silicate floating on the .surface of the molten iron is allowed to flow away as soon as it forms. The iron is run into no PHARMACEUTIC CHEMISTRY. channels made in sand, in which it sohdifies in bars known in commerce as pig iron or cast iron. Since cast iron is produced in contact with carbon, it con- tains a small amount of this element, both as ferric carbid and in the free state. Besides these, it usu- ally contains silicon, phosphorus, some sulfur and a little manganese. Cast iron, containing from 2 to 5% of carbon, is comparatively brittle, easily fusible and cannot be welded. By removing the silicon, phosphorus, sulfur, etc., which exist there as imj)uri- ties, we produce wrought iron which is a compara- tively pure form of iron. This is done by piling pig iron on the bed of a reverberatory furnace previously lined with ferric oxid, melting and thoroughly stirring the iron, when the impurities will become oxidized through the ferric oxid lining in the furnace, and will escape as sulfur dioxid, carbonic acid, phosphorus oxid, etc. Wrought iron contains less than 0.2% of carbon, is extremely malleable, infusible in the ordinary furnace, tough, and when heated to white heat it becomes pasty, so that two pieces when brought together while hot and hammered can be welded into one. Steel is produced by heating bars of wrought iron imbedded in layers of charcoal for sev- eral days, in which process, although the iron never melts, the carbon permeates it to the extent of 0.5 to 1.4%. This process is now employed only for the production of high-quality steel, and has been super- seded by the cheaper Bessemer process. This con- sists in blowing a current of air through molten cast iron until the impurities are burned out. To this purified metal a certain proportion of pure pig iron, preferably that containing manganese, like spiegel- eisen or jerromanganese, is added, together with a certain quantity of carbon. The carbon converts the iron into steel and the manganese serves to neutralize the untoward effects due to the small quantities of the oxids present. Steel is now manu- factured largely by the so-called "open hearth" method or Siemens-Martin process. This process consists in fusing cast iron in a reverberatory furnace much as in the puddling process,. next adding wrought iron to it and a small quantity of spiegeleisen, until the percentage of carbon is raised from 0.3 to 1.4%. Steel contains from 0.3 to 1.5%. of carbon which is chemically combined with the iron. It has a fine-grained structure; it is malleable and fusible in a furnace with a good draught; it melts at about 1400° C. Its most important property is that it can be tempered, that is, its hardness may be altered by the rate at which it is cooled. If, for example, when heated to redness, it is plunged into cold water, it is very brittle, but hard enough to scratch glass; if, however, it be allowed to cool gradually, it is almost as soft and malleable as wrought iron. From the above it will be seen that the tensile strength of pure iron is greatly increased by the admixture of small quantities of carbon, and the so carbonized iron is called steel. Spiegeleisen (mirror iron) is a white, very crystal- line cast iron, containing manganese as its chief constituent. 112 PHARMACKUTIC CHEMISTRY. Description. — Iron is a soft, white, lustrous metal with greatest magnetic and tenacious power. It fuses with difficulty, but welds easily. It is fibrous in structure, but becomes crystalline in time from continuous vibrating or jarring, in which case it has much less tenacity. In dry air it is oxidized only at high temperature. It will not oxidize in pure, water, but in moist air or when placed in water which has absorbed CO, from the air, it oxidizes quickly, the change being commonly called ''rusting." In contact with magnets, it becomes itself magnetic, but only tempered steel will retain this property for any length of time. Hydrochloric and sulfuric acids dissolve it freely and dilute nitric acid fairly easily, but concentrated nitric acid stops all solution till the "passive" condition is removed by heat or by coatact with certain metals. Compoiinds. — Iron forms both "ic" compounds, in which it is trivalent, and "ous" compounds, in which it is divalent. It is official in two forms: Iron (ferrum U. S. P.), metallic iron in the form of fine, bright and non-clastic wire (card teeth); and Reduced iron (ferrum reductum U. S. P.\ iron by hydrogen, alcoholized iron, Quevciinos iron, con- taining at least 90% pure iron. It is a line, grayish- black powder, made by heating iron liydroxid in h\drogen. Reaction: 2Fe(OH)3 + 3H, = Fc., -h 6H,0. Sdcclia rated iron carbonate (ferri carbonas sac- charatus U. vS.P.) should contain not less than 15% FERROUS SULFATE. II3 of FeCOg. It is a greenish-gray powder, sweetish, iron-like taste, not permanent, and should be kept in small, closely stoppered bottles. It is a mixture of sugar and ferrous carbonate, the latter prepared by double decomposition between ferrous sulfate and sodium bicarbonate. Reaction: FeS04 + 2NaHC03=FeC03-fNa2S04 + H,0+C02. The carbonate of iron is an ingredient in the pill, mass and iron mixture of the U. S. P. preparations. Iron sulfate (ferri sulfas U. S. P.), FeSO^ -|- 7H2O. Green vitriol, copperas, ferrous sulfate. Large, bluish-green colored crystals, soluble in 0.9 parts of water, and containing at least 99.5% of FeS04. It is made by dissolving iron in dilute sul- furic acid: Fe + H2SO4 = FeSO^ + Hj. It is used as a disinfectant in the arts and for the production of the ofi&cial dried and granulated iron sulfates. Dried jerrous sulfate (ferri sulfas exsiccatus U. S. P.), FeSO^. A white or gray powder, made by heating ordinary ferrous sulfate until it loses 35% in weight. It should be kept well stoppered. Granulated ferrous sulfate (ferri sulfas granulatus U. S. P.), FeSO„ 7H2O, was ofi&cial in the U. S. P., '90, as "precipitated" ferrous sulfate. It is merely a granular form of ferrous sulfate made by dissolving the commercial salt in hot water containing a little sulfuric acid, filtering, evaporating, chilling suddenly, draining the salt on a filter, washing with alcohol and permitting it to dry in an atmosphere of alcohol. Other ferrous compounds are the lactate (Fe- (CgHsOg).), tartrate (FeC^H^Og), phosphate {Fe^- 114 PHARMACEUTIC CHEMISTRY. (POJj), oxalate (FeQO;), chlorid (FeCU), iodid (Felj), this 'ast salt being the ingredient of the official syrup and pil of iron iodid (syrupus ferri iodidi) ; oxid (FeO) and hydroxid (Fe(OH)2), all possessing the usual properties of iron combined with the character- istics of the acid from which formed. The ferric compounds are more numerous and important than the ferrous compounds. Ferric chlorid (ferri chloridum U. S. P.), FeClg + 12H2O, muriate, perchlorid, or sesquichlorid of iron. Orange-yellow, crystalline masses or crusts, made by crystallizing a properly oxidized solution of ferric chlorid. A very deliquescent salt used as a chalybeate. It is made by dissolving iron wire in HCl and oxidizing the solution with HNO3: (i) Fe^ + 4HCI = 2FeCl2 -f 2H2. (2) 6FeCl., + 6HC1 + 2HNO3 = 6YeC\^ + 4H2O -I- 2(NO). An aqueous solution of ferric chlorid is official (liquor ferri chloridi U. S. P.). This solution should contain about 37.8% of anhydrous FeClg, correspond- ing to about 62.9% of the crystallized salt. A tinc- ture of ferric chlorid (tinctura ferri chloridi U. S. P.), made by diluting the solution with alcohol, is also official. The tincture should contain at least 13.28% of anhydrous salt which corresponds to 4.6% of metallic iron. Ferric hydroxid (ferri hydroxidum U. S. P.), Fe(OH)3, ferric hydrate, peroxid, hydra ted ferric oxid. Prei)ared by precipitating a solution of ferric chlorid with ammonia water and washing free from SCALE SALTS. II5 the ammonium chlorid formed; a brownish magma results. Reaction: FeClg + 3NH,0H = FeCOH), + 3NH,C1. Ferric hydroxid with magnesium oxid (ferri hy- droxidum cum magnesii oxido U. S. P.) — "arsenic antidote." This should be freshly made if it is to be used as an antidote in arsenical poisoning. Preparation. — By rubbing MgO, lo gm., in H2O, 800 c.c, gradually adding a mixture of ferric tersul- fate solution, 40 c.c, and HjO, 125 c.c, and mixing thoroughly. Dose, 120 c.c. Ferric hypophosphite (ferri hypophosphis U. S. P.), Fe(PH202)2. A grayish-white powder, nearly taste- less and slightly soluble. Used in making syrup of hypophosphites comp. (syrupus hypophosphitum compositus U. S. P.). Used as a hematinic Iron and ammonium stdfate (ferri et ammonii sulphas U. S. P.), FeNH,(S0,)2 + 12H2O. Iron and ammonia alum, iron alum. Pale violet^ octa- hedral crystals, odorless, styptic taste, efflorescent. Should contain 99.5% pure salt, corresponding to 11.5% of -iron. Prepared by dissolving ammonium sulfate in solution of ferric tersulfate, evaporating and crystallizing. Reaction: Fe2(SO,)3 -f- (NH,)2SO, = 2FeNH,(SO,)2. SCALE SALTS. — These compounds are usually prepared by dissolving ferric hydroxid in a corre- sponding organic acid, evaporating to syrupy consist- ence and spreading on glass plates, from which it flakes or scales on cooling. All scale salts are ferric salts. Il6 PHARMACEUTIC CHEMISTRY. There are nine official scale salts: Soluble ferric phosphate (fcrri phosphassolubilis),iron 12% ; soluble ferric pyrophosphate (ferri pyrophosphas solubilis), iron 10%; ferric citrate (ferri citras), corresponding to 16% iron; iron and ammonium citrate (ferri ct ammonii citras), corresponding to 16% iron; iron and ammonium tartrate (ferri et ammonii tartras), corres- ponding to 13% iron; iron and potassium tartrate (ferri et potassii tartras), 15% iron; iron and quinine citrate (ferri et quinins citras), 13.5% iron; soluble iron and quinine citrate (ferri et quininae citras solu- bilis), i3.5'/( iron; iron and strychnine citrate (ferri et strychnina; citras), 16% iron. The soluble phos- phate and pyrophosphate are green in color, the other seven being garnet-red to reddish-brown. With the exception of iron citrate and the iron and quinine citrate, which are very slowly soluble in water, all the scale salts of iron contain alkalin citrate or tartrate, purposely added to enhance their solubility, and are usually designated as "soluble." All the official liquors of iron contain ferric salts. Dialysed iron (ferrum dialysatum) is made by dissolving crystalline ferric chlorid in the solution of ferric chlorid and subjecting the mixture to dialysis, liy this ])roccss the remaining free acid is removed, leaving a colloidal basic salt composed of 99% of ferric hydroxid and 1% of hydrochloric acid. Iron and its salts are not poisonous. Tests. — Iron may be detected by a red ]>recipitate with ammonium hydroxid, a bnnvnish-black pre- cipitate with hydrogen sulfid. et( . ALUMINUM. I I 7 Distinctive tests between jerric salts and jcrroiis salts: REAGENT FERRIC SALTS. FERROUS SALTS. Potassium ferrocyanid, Dark-blue precipitate Light-blue precipitate Potassiurri ferricyanid, Brownish color; no Dark -blue precipitate. precipitate formed. Potassium sulfocyanid, Dark, blood-red color- No change of color ation. (with impure ferrous salts turns reddish). Alkalis, Brownish precipitate. Green precipitate, turning brown on the surface. ALUMINUM, Al, 27. Sp. gr., 2.5. Occurrence. — Aluminum is the most abundant metal, and of all the elements it is only exceeded in abundance by oxygen and silicon. It is never found native and until comparatively recently it was difficult to extract from its combinations. It occurs as a silicate in clays, kaolin, feldspars, micas, granite, porphyry and many crystalline rocks. As an oxid (AI2O3), it is found in the ruby, sapphire and in corundum and emery. Cryolite is the double fluorid of aluminum and sodium (Al2Clg,6NaCl), and bauxite is an hydrated oxid (Al203,H20), both of which are largely used for the production of aluminum. Preparation. — (i) By reducing of the ores with carbon by the intense electric -furnace heat; (2) by treating cryolite with metallic sodium (Deville's process). Reaction: Al2Cle ,6NaCl + aNa, = W, -f 12 NaCl Cryolite Properties. — A white, silvery metal, very tenacious, malleable and ductile. It is very light, but strong and rigid; is an excellent conductor of heat and electricity, almost equal to silver in this respect. It is affected but little by air, gases or ordinary Il8 PHARMAt'EUTIC CHKMISTRY. acids, but is readily dissolved by caustic alkalis. It melts at 625° C. It does not tarnish in the air and is not affected by hydrogen sulfid. Aluminum forms valuable alloys and is much used in the arts. It is also becoming of great value in numerous commercial and domestic wares. Aluminum bronze (copper, 90; aluminum, 10), is one of the alloys of aluminum valued for castings and superior to brass in tensile strength. Steel is improved by the addition of 0.1% of aluminum. Aluminum acts as a trivalent element. The alums are important compounds of aluminum. The general formula of the alums is RR'(S04)2, 12H2O — the R representing Al, Cr, Fe or j\In, and R' one of the alkali metals. They all crystallize as octahedra. Akim (alumen U. S. P.), A1K(S04)2 + 12H2O. Alum, potash alum. Purity, 99.5%. Large, odor- less, colorless, octahedral crystals, with astringent taste. Soluble in 9 parts of water. Incompatible with alkali hydroxids, carbonates and phosphates, and chlorids of the heavy metals. Other alums are the ammonia alum, AINH^(S04)2 + laHjO, simi- lar to potash alum, a double sulfate of ammonium; iron alum, chrome alum, manganese alum, etc., in which these respective metals replace the aluminum in the molecule. Preparation. — Official alum is made by calcining alum-shale (alum clay, aluminum silicate) with iron pyrites, which operation results in the forma- tion of sulfuric acid, which acting on the silicate ALUMINUM COMPOUNDS. II9 produces aluminum sulfate. This, together with the sulfates of iron is extracted with water. In this liquid potassium chlorid is dissolved which interacts with the iron sulfates, becoming converted into potassium sulfate, which combines with aluminum sulfate and which crystallizes with 12 molecules of water of crystallization. Exsiccated Alum (alumen exsiccatum U. S. P.)' AlK(SOj2, dried or burnt alum, alumen ustum- Purity, 99%. A dry, porous mass or powder, odor- less, sweetish, astringent taste, nearly twice as strong as the official alum, attracting moisture. It is soluble in 17 parts of water, 1.5 parts of boiling water. Preparation. — By merely driving off the water of crystallization from alum. The alums are all used as caustic astringents. Aluminum salts precipitate organic colors, forming with them pigment "lakes," etc. This important property is utilized in dyeing, where alumina (Al(OH)3) becomes deposited in the material to be dyed and acts as a "mordant," "binder" or "fixer" of the dyes employed. Aluminum hydroxid (alumini hydroxidum U. S. P.), Al(OH)3, alumina. A white, light, amorphous powder, permanent, odorless and tasteless, made by treating a soluble salt of aluminum with an alkali hydrate or carbonate: 2AIK(S04)2 + aNajCOg + 3H2O = 2AI(OH)3 + K2SO, + sNa^SO, + 3CO3. It is used as a mechanical protective filtering me- dium and for preparing the sulfate of aluminum. Aluminum sulfate (alumini sulphas U. S. P.), Al,- I20 I'llARMACFAITIC CIIK.M ISTKY. (804)3 + ibHjO; 99.5% pure. It is a white, crys- talline powder, flakes or fragments, odorless, sweet- ish, astringent taste, soluble in one part water. Loses crystalline form at 200° C. In medicine, aluminum sulfate should not be confounded with alum. A commercial aluminum sulfate (alum cake) is some- times called "concentrated alum" and contains but 12 molecules of water of crystallization. Aluminum forms chlorid (AICI3), oxid (AljOg), bromid (AlBrg), iodid (AII3), fluorid (AIF3). Spinel is native magnesium aluminate (MgAljO^). Other aluminates are known, but they find but little appli- cation in the arts. The most important utilization of the aluminum clays is in pottery and ceramics. Thus, porcelain, earthenware and stoneware are prepared from native aluminum compounds; porcelain from kaolin, feldspar or quartz; earthenware from clay or feld- spar and silica; stoneware from clay containing ferric oxid and lime. Cements and mortars, which are manufactured from the lime-clays and similar arti- ficial mixtures, may here be mentioned: When burnt (calcined) lime is treated with water, it "slakes." When such slaked lime is alone used as a mortar, it sets and slowly hardens, but in the process of setting it cracks, thus making its use as mortar unprofitable. When, however, it is mixed with some substance which tends to counteract this excessive shrinkage, it forms a good mortar. Sand or silica (SiO,) is a good admixture for this purpose if mixed with the lime in proper proportions. The setting of mortar is due to the loss of moisture (water is formed in the process of setting, thus: Ca(OH)2 + CO2 = CaCOg + H,0, this accounting for the per- sistent dampness of newly built houses in which the mortar is setting), and the hardening is due to absorption of carbon dioxid from the air which in time converts the lime to limestone. In this reaction the lime superficially attacks the surfaces of the sand grains, converting these into calcium silicate which further solidifies the mortar, making it in time a stone-like mass. For this purpose angular sand grains are preferred to the well-rounded pebbles. Roman cement is made by calcining calcareous clay which must be "fat" (free from magnesia) at a temperature just below sintering. Portland or hydraulic cement is made by calcining mixtures of. limestone with clay (or other materials containing aluminum, silica and lime) and finely grinding ■ the resulting clinker-like mass. When mixed with water, cement should not be allowed to stand, but should be appHed at once. The setting of cement is supposed to be due to the formation of crystalHne silicates and aluminates of calcium, which form a hard stone-like mass. Good Portland cement should contain from 55 to 60% of lime, 22 to 26% of silica and 7 to 8% of alumina. Concrete consists of hydraulic cement mixed with crushed rock or pebbles. Aluminum and its salts are nonpoisonous. Tests. — Aluminum may be detected by precipi- tation with ammonia, as hydroxid soluble in alkali 122 PHARMACiaTTIC CHEMISTRY. hydroxids and rejjrecipated hy NH^CI; alsci by fusion on charcoal with cobalt nitrate, giving a rich blue color to the mass. CHROMIUM, Cr, 52. Sp. gr., 6.8. Occurrence. — Chromium is not found free, but occurs most commonly in chromite, also called "chrome iron ore," a ferrosochromic oxid, Cr203- FeO. It is separated with difficulty from the ore, and is usually prepared by the reduction of chromium sesquioxid with charcoal in the electric furnace. Properties. — It is a hard, glistening, steel-gray metal, very fusible, magnetic at low temperatures, oxidizes only at a high heat, is soluble in hydrochloric acid and strong alkalis. Alloys of chromium are admixed with steel to increase the strength of the latter. Chromium acts both as an acid and a basic radical, forming compounds in each capacity. As a base it exerts trivalent, tetravalent and h^exavalent properties, forming "ous" and "ic" salts. It forms two oxids well defined — the chromic oxid (CrjOj), a green, insoluble powder used as pigment in glass and porcelain making; and chromic anhydrid or trioxid (chromii trioxidum) (CrOg), previously im- properly known as "chromic acid." Preparation. — From ])otassium dichromate and sulfuric acid: KjCr,©; + HjSO, = 2Cr03 -\- K2SO, + H2O. Saffron-colored needle crystals, very hy- groscopic, very strong oxidizing agent. Decom- poses organic solvents, such as alcohol or glycerin, with dangerous violence. It is used as a caustic. CHROMIUM. 123 With water it forms cliromic acid (H^CrO^), from which a series of salts are produced: H,0 + CrOg = HjCrO^. A second acid may be produced by removing water from ordinary chromic acid. Thus: 2H,CrO, — H2O = H2Cr207, the series of salts are known as dichromates (bi- chromates), and the principal one is the potassium salt — potassium dichromate, also called bichromate or red chromate (potassii dichromas U. S. P.), K,Cr,07 (K,CrO,,Cr03). Potassium dichromate is prepared from potassium chromate and su'furic acid. Reaction: aK^CrO^ + H^SO, = K^Cr^O^ + K^SO, + H^O. It occurs as a reddish, crystalline salt. Potassium chromate, K2CrO^ yellow chromate of potash, is made by roasting chrome iron ore with potassium carbonate and lime. Reaction: 2FeO,Cr203 + 3K2CO3 + CaO + 70 = CaCrO, + Fe^Og + 3K,CrO, + 3CO,. The yellow chromate is more soluble than the di- chromate; both salts are much used in the arts and chemically as strong oxidizing agents, especially the latter. Lead chromate (chrome yellow), PbCrO^, is found native as crocoisite. It is prepared by pre- cipitating soluble lead salt with potassium dichromate; barium chromate, BaCrO^, is prepared similarly. Both are used as yellow pigments. Chromic sulfate (chrome alum) has the formula CrK(S04)2,i2H20. By adding ammonia to chrome alum the greenish hydroxid Cr(0H)3 is obtained, which on ignition yields the sesquioxid Cr203, which, 124 PllAKMACF.UTlC CHKMISTRV. under tlie name of chrome green, is employed as a green pigment. Another pigment is "Guignet's Green," a hydroxid obtained by heating potassium dichromate with boric acid and extracting with water. Both the yellow and green pigments of chromium, being very insoluble, are highly valued and some of these are used in the printing of the United States paper money. Chromyl chlorid, CrOjClj, a red, fuming liquid, is obtained by distilling a mixture of potassium dichromate and sodium chlorid with sulfuric acid. Chromic chlorid, Cr2Clg, is obtained by acting with chlorin on a heated mixture of chromic oxid and carbon. Toxicology. — Chromium compounds, especially the dichromate of potassium, are irritant poisons and may produce either acute or chronic poisoning. Emetics should be promptly administered followed by magnesium carbonate and demulcent drinks-. Tests. — Soluble chromium compounds may be detected jjy the greenish precipitate formed with ammonia, or by the solutions of soluble lead salts which produce the yellow chromate of lead. The insoluble salts may be recognized by the borax bead which, in the oxidizing flame, is reddish when hot, yellowish-green when cold, and in the reducing flame it is green. CHAPTER XIV. COBALT, NICKEL, MANGANESE, ZINC. As already stated, these metals c()ni])nse the second division of the ammonium sultid group. They are precipitated by ammonium sulfid, in the presence of ammonia water and ammonium chlorid, as sul- fids and separated as such. The ammonium chlorid plays the part of a solvent for the metals of the later groups and prevents their precipitation. The first two metals, cobalt and nickel, are of but little value pharmaceutically and have no official preparations. In chemistry, the arts and manufactures, howeverj they are more important. Manganese and zinc, on the other hand, are of much more importance, both pharmaceutically and in the arts. COBALT, Co., 59.5. Sp. gr., 8.9. Occurs native only in meteorites. Its most im- portant ores are spiess-cobalt, or "smaltine," CoAsj; cobalt glance, or "cobaltite," CoAs^CoSo, and the arsenical sulfid, CoAsS. The metal is obtained by reduction of the chlorid with hydrogen, but the processes emploved are com- plicated. Cobalt is a lustrous-white, tenacious metal, malle- able and, when heated, quite ductile. It melts with difficulty. It becomes magnetic and holds this 125 126 PHARMACEUTIC CHKMISTRY. ])n)])LTty even when heated to redness. It is unal- tered in the air excej)! in very fine powdered form. It forms three oxids: cobaltous oxid, CoO, a drab-colored powder, obtained by reducing the ses- quioxid; cobaltic oxid, CojOg, and cobalto-cobaltic oxid, C03O4, also several others of less importance. It also forms cobaltic hydroxid, Co(OH)2, when pre- cipitated with the caustic alkalis, cobaltous chlorid, C0CI2; cobaltous sulfate, CoSO^ + 7H2O, etc. Cobalt also forms a large number of complex ammoniacal cobalt compounds, which will be men- tioned later. When cobalt compounds are fused with borax, a clear, blue, glassy bead is produced, and a similar blue is imparted in the same way to ordinary blue glass, due to the formation of silicates of cobalt. This cobalt silicate, finely ground, forms a pigment known as "smalt," and is employed in decorative arts. Cobalt chlorid in solution forms "sympathetic inks" — invisible until heated. With NaOH, the salts of cobalt yield a blue precipitate, which on boiling is converted into the hydroxid. NICKEL, Ni, 58.7. Sp. gr., 8.9. The i)roperties of nickel are so similar to coljalt as to require no special discussion. The principal ores of nickel are niccolite, NijAsj, and nickel glance, NiAsjNiSa- The metal is obtained by reducing the oxid with carbon or by hydrolysis. The compounds of nickel correspond to those of cobalt. Nickclous oxid, NiO; chlorid, NiCl.,; sulfid, NiS. Nickel linds much use in alloys and electroplating. MANGANESE. 127 Nickel imparts a red-brown color to the borax bead in the oxidizing flame, and gray opaque in the reducing flame. The presence of cobalt masks these colors entirely and must be removed before a flame-test for nickel is made. MANGANESE, Mn, 55. Sp. gr., 7.2 Never found native in the metallic state, but it is widely distributed in combination with oxygen as pyrolusite, Mn02; hraunite, yin^O^; haiismannite, Mn304; also as manganUe, Mn203,H20, and as spar, MnC03. The metal may be obtained by reducing its ores with charcoal. Manganese is a hard, steel-gray, Ijrittle metal, oxidizes readily in the air, and is readily acted upon by hydrochloric and sulfuric acids. The metal finds but little use in the free state, but as an alloy with iron, spiegeleisen and jerromanganese, it is used in steel making. Manganese combines the properties of both a metal and an acid. Manganese forms "ous" com- pounds, MnR2; "ic" Mn2Re, and salts of manganic acid, H2Mn04, called manganates. It forms the usual series of salts of all three types. The precipitated black oxid (mangani dioxidum precipitatum U. S. P.), MnO., should be at least 80% pure. Description.— Hea.\y black powder, odorless, per- manent. Used as a catalytic to produce oxygen from potassium chlorate, and, heated with sulfuric acid, loses its own oxygen and forms manganous sulfate, commonly known as pink vitriol. 128 PHARMACKUTIC CHEMISTRY Mauganese hypophosphite (mangani livpoj)hos- phis U. S. P.), Mn(PH202) +H2O, is official. Description. — Pinkish-white crystalHne powder, odorless and tasteless, soluble in 6.5 parts water; at least 79% pure. The hypophosphite is used as a tonic and enters into the syrup hypojjhosphites compound. Manganese sulfate (mangani sulphas U. S. P.), MnSO^ + 4H2C). Manganese sulfate. Pink vitriol. Purity, 99.5%. Preparation. — PVom the dioxid with sulfuric acid; Reaction: 2Mn02 + 2H2SO, = 2MnSO, + 2H2O + O2. manganous sulfate Description. — Transparent, pale, rose-colored crys- tals, odorless, but bitter astringent in taste, readily soluble, used as a hematinic. The derii'atives of manganic acid, are analogous to salts of sulfuric acid, the manganese acting as a hexad. The manganates are not permanent, but are readily convertible into the permanganates. The most common permanganate is the salt of potas- sium. Potassium permanganate (potassii permanganas U. S. P.), KMnO^, is prepared from the dioxid. The reaction takes place in two stages: (i) 6KOH-t-KC103 + 3Mn02 ^ sMInO, -|- \r 0\ 1 ~,\i r\ manganese potassium KV^l i- 3112^^- dioxid manganale The green manganate of potash, KjMnO,, is then changed to permanganate b\- extracting the mass ZINC 129 with boiling water, cooling and passing chlorin into it: (2) 2K2MnO, + CL, = 2KCI + 2KMnO,. potassium permanganate The solution is then crystallized. The perman- ganate forms dark-red, almost black, rhombic prisms. It has very strong oxidizing properties, and finds much use in this capacity as a disinfectant, deodorant and antiseptic solution. It decomposes with organic substances; pills of the permanganate are best made by triturating the salt with kaolin and massing with petrolatum. ZINC, Zincum, Zn, 65. Sp. gr., 6.8-7.2. This element always occurs in combination. Its compounds are only fairly abundant. The most important zinc ores are the carbonate, a//- (//^//;/f, ZnCO.,; the sulfid, or zinc blende, sphalerite, ZnS, and red-zinc ore, ZnO, found in New Jersey, as is also jranklinite, (ZnFe)OI''e203. The ])r<)cess of extraction usually consists of two ste])s: (i) roasting to convert into an oxid, and (2) mixing this with carbon and igniting in earthenware retorts, and thus reducing the oxid. The i)rocesses vary according to the nature of the ores. The crude metal so obtained is known as "spelter," and is contaminated with iron, lead, arsenic, cadmium, etc. It is purified from these by a second distillation. Arsenic is a commonly found impurity, even in the better grades. Zinc is a bluish-white, highly crystalline and brittle metal which can be pulverized. {Zinc-dust is so 9 130 PHARMACKUTIC CHEMISTRY. prepared.) \N'hen heated l)et\veen 150° and 200° C, zinc is malleable and ductile, and at still higher temperatures it again becomes brittle. Zinc fuses at 412° C, and distills at 940° C. It dissolves readily in dilute acids forming corresjxjnding salts and liberating the hydrogen of the acids. It is also soluble in alkalin hydro.xids, forming Zincates. Since it is not affected by the air, it finds much use as an outside coating, such as the "galvanizing" of iron, etc. Zinc is official (Zincum) and is required to be at least 99% pure and free from arsenic. Granulated zinc is made by pouring molten zinc into water. The zinc allovs with copper, such as brass, are valued and are much used. It also alloys with tin, copper and antimony in all proportions, but with lead and bismuth in definite proportions only. German silver is an alloy of copper, zinc and nickel. The present Pharmacopoeia recognizes the follow- . ing zinc compjounds: Zinc acetate (Zinci acetas U. S. P.), Zn, (C.HjO,), — 2H2O; 99.5% pure. Zinc hromid (zinci bromidum), ZnBr.,; 97',, pure. Zinc carbonate (zinci carbonas precipitatus), which should yield not less than 72% of zinc oxid. Zinc chlorid (zinci chloridum), ZnCU; 99.5% pure. Zinc iodid (zinci iodidum), Zniz, when anhydrous, should contain not less than 98% of pure zinc iodid. ZiJic oxid (zinci oxidum), ZnO; at least 99-5^V pure. zINC. 131 Zinc phenoJsidjonate (zinci phenolsulphonas), Zn(C6H5SOj2,8H20; the uneffloresced crystals should contain at least 99.5% of the pure salt. Zinc stearate (zinci stearas), Zn(Ci8H3502)2- Zinc sulfate (zinci sulphas), ZnSO^ + yHjO; 99.5% pure, "white vitriol." Zinc valerate (zinci valeras), Zn(C5H902)2 + 2H20; 99% pure. Of the above zinc salts, all are soluble in water and poisonous, except the carbonate, stearate and oxid. The last of these three finds much use in paints as a pigment, together with lead carbonate, to give the latter greater lasting qualities. The zinc salts are prepared by acting upon the metal or its oxid or carbonate uith the corresponding acid. The action of the zinc salts is due largely to the acid present in the compound and they are there- fore astringent, antiseptic or disinfectant, as the case may be. Toxicology. — All soluble zinc salts, as stated, are poisonous. The chlorid is used by tinsmiths, also in embalming and as "Burnett's disinfecting fluid." In all these it acts as corrosive. The best zinc antidotes are soap, milk and soluble alkali car- bonates, or substances containing tannin, such as tea or coffee. Tests. — With alkalin carbonates or hydroxids, zinc compounds in solution give a white precipitate soluble in excess of the reagent. Potassium ferro- cyanid gives a yellowish-white precipitate, insoluble in dilute hydrochloric acid. CHAPTER XV. BARTOM, STRONTIUM, CALCIUM. THE CARBONATE GROUP. The three metals of this group possess quite similar properties. They form insoluble carbonates in ammoniacal solutions, even in the presence of ammonium chlorid, which is present here to prevent the precipitation of magnesium at the same time. They form insoluble carbonates, and hence the name "carbonate group." Magnesium, through the inter- vention of ammonium chlorid, is placed in the next group, although it has many properties in accord with the members of this group. The members of the carbonate group, with the ex- ception of calcium, are not of interest pharmaceuti- callv, for there are no official salts of barium, since barium dioxid was dropped, and strontium has but three recognized salts. There are, however, ten com- pounds of calcium official and many more commonly used. BARIUM, Ba, 137.2. Sp. gr., 4. Barium docs not occur native, and the metal is so difficult to isolate that some doubt exists a^ to whether strictly pure barium has ever been i)roduce(l. Its most al)undant natural compounds are heavy spar, BaSO^, a.m\ icithcrite, BaCO.,. 132 STRONTIUM. 133 Barium forms two oxids, BaO and BaOj. Barium dioxid, BaUj, is a grayish-white powder, decomposed by dilute acids, and this property has made the salt valuable in the preparation of solutions of hydrogen dioxid; thus: 3Ba03 + 2H3PO, = 3H3O2 + BagiPO,)^. hydrogen dioxid Barium nitrate, Ba(N03)2, finds use only as a reagent and for producing "green fires" (Bengal lights). Barium sulfid, BaS, is prepared by reducing the sulfate liv heating with coal dust. The salt is soluble in water and used as depilatory. Barium chlorid, BaCl2, and barium carbonate, BaCOg, find use as chemical reagents only. Toxicology. — SoliiUe salts of barium are poisonous, though but few cases of poisoning with barium ever occur. Any soluble sulfate, such as sodium or magnesium sulfate, when given, form with barium, insoluble sulfates, w^hich should be removed with emetics. Tests. — Barium salts are readily precipitated from their solutions with soluble carbonates or sulfates, and the sulfate so formed is insoluble in acids. Chromates also produce an insoluble, primrose-yellow barium chromate; distinction from calcium and strontium, which form soluble chromates. STRONTIUM, Sr, 87.3. The principal minerals of strontium SLvestronti initc, SrCOg, and celestite, SrSO^. These ores are found but sparingly. Strontium is found in verv small 134 PHAKMACKUXrC CHEMISTRY. (juantities in gvpsuni, some limestones and mineral waters. Description. — Strontium is a yellow, lustrous metal, and resembles barium and calcium in most properties. Strontium compounds impart a red color to the flame, and the nitrate is much used in pyrotechny as the principal constituent of "red fires." Strontium salts are not considered as poisonous except in large quantities. As stated, there are but three salts officially recognized. Strontium bromid (strontii bromidum U. S. P.), SrBr2,6H20. Purity, 97%. Description: Colorless, transparent crystals, very deliquescent, soluble in one part of water. Used in medicine as a sedative nervine. Strontium iodid (strontii iodidum U. S. P.), Sri, + 6H2O, should be at least 98% pure. Description. — Colorless, transparent plates; deli- quescent and not permanent in the air. Soluble in 0.5 part of water. Used as an alterative. Strontium salicylate (strontii salicylas U. S. P.), SrCC^HsOg), + 2H,0. Purity, 98.5%. White, crys- talline powder, soluble in 18 parts of water. Used medicinally as an antirheumatic and antiseptic. All the strontium salts are prepared by acting upon the carbonate or hydroxid with the respective acid solution. Tests. — Strontium may be detected by the crimson color imparted to the flame. With sulfuric acid, strontium salts form insoluble sulfates. CALCIUM. 135 With soluble carbonates or t)xalates, strontium salts give insoluljle precipitates. The precipitated sulfate is insoluble in solution of ammonium sulfate (distinction from calcium). CALCIUM, Ca, 40. Sp. gr., 1.6. Calcium does not occur free, but is very widely distributed in its compounds. The carbonate, CaCOg, in limestone, marble and chalk, the sulfate, CaSO^, as gypsum and alabaster, and the phosphate, CaH^(P04)2, silicate, CaSiOg, and fluorid, CaFa, are most widely distributed minerals. Some of these compounds occur in most natural waters and soils and also in vegetable and animal tissues. Bones consist largely of calcium phosphate. The element was first isolated by Davy (1808), the most common means of separation now being through the electrolysis of the fused chlorid. Properties. — Calcium is a pale, brass-yellow colored metal, hard but malleable; acted on easily by moist air, burns readily when heated in air, and decomposes water. Compounds. — The compounds of calcium are numerous and of much value commercially as well as pharmaceutically and medicinally. Ten salts or compounds are recognized in the Pharmacopeia. Calcium bromid (calcii bromidum U. S. P.), CaBrj; 97% pure. Preparation. — From the carbonate with hydro- bromic acid. Reaction: CaCO, + 2HBr = CaBr, + H,0 + Co^. 136 I'lIAKMACKl TK: CHExMISTRY. Very soluble. All the other salts of ralriiiin maybe prepared in a similar icay. Calcium hypophosphite (caleii hypophosphis, U. S. P.), Ca(PH,()2).; 98% pure. This is prepared by warming calcium hydroxid with ])hosph{)rus and water. In preparing this salt great care must be used, as phosphin, PH,, a highly explosive gas is formed, and good draughts are necessary to carry it off. The temperature employed should not exceed 85° C. 4P2 + 3Ca(OH)2 + 6H3O = 3Ca(H,PO.>\ + 2PH,. calcium hypophosphite Quicklime (calx U. S. P.), CaO. Calcium oxid. Lime. Description. — Hard, white or gray masses; soluble in 760 parts' of water. In air it slowly absor])s moisture and falls to a gray powder (air-slaked lime, CaOH).,). With water this change takes place rapidly. Quicklime is manufactured from limestone — native calcium carbonate, CaCC), — by burning in kilns (narrow furnaces, usually of brickV to remove carbon dioxid. Thus: CaCOa = CaC) + CO,. limestone lime or marble Lime is noncombustible, and when heated in the oxyhydrogen flame it emits a brilliant light known as the "lime light." It is much used as a drying agent on account of its affinity for water. When slaked as described, it becomes a hydroxid which is slightly soluble, and solutions of this arc known as lime MMK. 137 wafer (li(|U(>i- calcis U. S. P.) which should contain at least 0.14% of the hydroxid. The hydroxid, citrate and oxalate of calcium are more soluble in cold than in hot water. "Milk of lime" is a pasty mass of calcium hydroxid with water, made by slaking lime, the lime being in excess. Lime also enters into building mortars where its cementing property is due to the absorption of carbon dioxid from the air whereby the calcium carbonate forms. Chlorinated Lime (calx " chlorinata U. S. P.), Ca(OCl)Cl. lileaching powder, bleach, "chloride of lime." It should, when assayed, yield not less than 30% of available chlorin. It is prepared bv the action of chlorin on slaked lime. When treated with water, the following reaction occurs: 2Ca(0Cl)Cl = CaCls + Ca(0Cl)2. When treated with acids, chlorin is generated: Ca(OCl)Cl + H,SO, = CaSo, + H^O + CU. Chlorinated lime is used as a disinfectant, deodorant and as a bleaching agent. It enters into the solution of chlorinated soda, commonly called " Labarraques" (liquor sodae chlorinatae) which should contain at least 2.4% of available chlorin. Suljurated lime (calx sulphurata U. S. P.), suf- furated lime, crude calcium sulfid, is a mixture con- taining at least 60% calcium sulfid, with sulfate and carbon. Made by heating together 70 parts of dried calcium sulfate, 10 parts of charcoal and 2 parts of starch to redness until the mass loses its black color. Then it is pulverized and should be preserved tightly stoppered. 138 PHARMACKITIC CHEMISTRY. Calcium carbid, ('aC., unoftuiul, is prepared in an electric furnace from coal tar and lime. It decomposes in contact with water, furnisliino; acety- lene gas, according to the equation: CaC, + 2H.,0 = QH^^ + Ca(()H).,. acetylene Precipitated calcium carbonate (calcii carbonas precipitatus U. S. P.), CaCOg, ])recipitated chalk; purity gg^; : The salt is made by precij)itating calcium chlorid with a soluble carbonate, as sodium: CaClj + Na^COj = CaCOg + 2NaCl. This is a purer salt than prepared chalk (creta pre- parata U. S. P.), CaCO, — a white or gray powder or moulded conical drops, made by elutriation. The prepared chalk is less crystalline and smoother than precipitated chalk, and hence is directed in preparations for internal administration. "Paris white" and "whiting" are synonyms for the impure prepared chalk, l)oth arc used in polishing mixtures, etc. Calcium chlorid (calcii cliloridum U. S. P.), CaCU; 99% pure. Description. — Anhydrous, white, fused masses; very deliquescent, readily soluble. Its greatest value is as a drying agent, due to its great atTmity for water, which it will absorb from gases or liquids. Precipitated calcium phosphate (calcii phospl as l)recipitatus, U. S. P.), Ca.,(P()^y^. Bone phosphate, normal calcium ortho])hosphatc; purity, 99%. A permanent, white, insoluble powder. The salt occurs in the phosphate rock of I'Morida and South CALCIUM COMPOUNDS. 139 Carolina, in which it is sometimes found u]) to 90%. The "precipitated phosphate " is made by adding calcium chlorid and ammonium hydroxid to phos- phate, known as "white rouge." A number of phosphates are formed with calcium, such as tricalcic phosphate, bone phosphate, dical- cium phosphate, Cx^U^iFO^)^, and monocalcium phosphate, CaH4(POj2 "superphosphate." The rock phosphate is used extensively as a valuable fertilizer. Calcium sulfate, CaS04 + 2H2O. Crystalline, sparingly soluble, called gypsum, selenite and "terra alba." Heated to 120° C, it gives up its water, becomes an opaque mass, which, when ground, constitutes the official "plaster of Paris" (calcii sulfas exsiccatus, U. S. P.), CaS04, "dried gypsum." The "plaster of Paris" still contains about 5% of water. When mixed with water, it reabsorbs two molecules of it and hardens to a stone-like mass. Upon this property depends the value of plaster of Paris in preparing surgical dressings, moulds, etc. Calcium salts are not poisonous and, in fact, are found normally present in every part of the human body, in tissues, fluids of the body, etc., being most abundant in the bones and teeth — bones containing about 55% and teeth about 72% of calcium salts. Tests. Calcium may be detected in solution by its insoluble carbonates, sulfates and especially its oxalate precipitates, which are formed with the. soluble salts of the corresponding acid. With Bunsen flame it gives a brick-red coloration. CHAPTER XVI. THE ALKALI-METAL GROUP. Lithium, 7 Rubidium, 85 Sodium, 23 Cesium, 133 Potassium, 39 Ammonium, 18 We have no general reagent for the metals of this group. Each member is separated or detected in- dividually. Their grouping together is due to a number of characteristics, which they possess in conimon. Thus: All have a low specilic gravity; are monatomic; soft and easily fusible; have great afiinity for o.xvgen and decompose water, forming hydroxids which dis- solve in excess of water. These hydroxids turn red litmus blue, neutralize acids, saponify fats and, if strongly concentrated, are caustic .to the point of eschar. These properties, characteristic of alkalis, give the name of "alkali metals" to the mcml)ers of this grouj). Their great affinity tor oxygen causes them to oxidize in the air, to tarnish immediately and even to take fire, due to the heat produced by the ra])id oxidation. They are, therefore, kept beneath a mineral oil, free from oxygen, to prevent ra])id oxida- tion. Lithium, .sodium and jxttassium were discovcreil in 140 LITHIUM. 141 1807-1808 by Sir Humphrey Davy, and cesium and rubidium by Kirchoff and Bunsen in 1860-1861. The relation between the atomic weights is an in- teresting point. There is a difference of 16 in the atomic weight of lithium and sodium; the same be- tween sodium and potassium; practically three times sixteen between potassium and rubidium and between rubidium and cesium. This seems to show them to lie in an homologous series, with two undiscovered metals belonging in the spaces on each side of rubidium. These metals form many salts, but only one chlorid, bromid and iodid. As a general state- ment, it may be said that the salts of alkali metals are white, crystalline compounds, soluble, odorless, characteristic in taste and permanent. LITHIUM, Li, 7. Sp. gr., 0.589. Occurrence. — Lithium occurs widely distributed, but in very small quantities, as in mineral springs, in plants, especially in tobacco and the beet. It is usually separated from its chlorid by electrolysis. Properties. — A silver-white matal, fusible at 180° C, burns with an intense red flame. It is the lightest metal of the solid elements. Compounds. — The salts of lithium so closely re- semble those of sodium as to require no separate dis- cussion. Those recf)gnized officially are: Lithium bromid (lithii bromidum U. S.P.), LiBr.; purity, 97%. Used as a sedative nervine. Lithium carbonate (lithii carbonas U. S. P.),Li2C03; 142 I'flARMACEUTlC CHEMISTRY. purity, 98.5^^- Made according to the following re- action: LijSO. + lNHj.COg = Li,C03 + (NH,)2SO,. lithium^ carbonate. Used as an alkalin diuretic. Lithium citrate (lithii citrus U. S. P.), Li-jC^H^O^ -(-4H2O; purity, 98. s*^'^. Preparation from the car- bonate: sLi^CO,, + 2H3C6H5O7 = 2Li3C6H507 + 3H,0 + 3CO3. Used as a diuretic. This salt forms with uric acid a salt, which is the most soluble of all its com- pounds; hence the use of lithium in uric-acid j)oisoning.' It enters into (lithii citras effervescens, 5%) the effervescent citrate. Lithium salicylate (lithii salicylas U. S. P.), LiC^H^O^; purity, 98.5'^{. Used as an antirheu- matic. Lithium bciizoate, (lithii benzoas U. S. P.), LiC7H502; purity, 98. 5^;, . The salt is used as an intestinal antiseptic. • As may be readily seen, all the salts of lithium may be prepared by the action of the res])ectivc acid upon lithium carbonate. The phys- ical characteristics of the lithium salts are so similar to those of sodium that in general the descrij)tion oi the corresponding sodium salt will apply to lithium as well. Sec later description under Sodium. POTASSIUM, Kalium; K, 39. Sp. gr., 0.865. (^Ciiinrucr.- Widely distributed in rocks and minerals, particularly as syh-itc, KCl, and carnallitc, KCl, MgCU,6H/); found in the mines of Stassfurt, POTASSIUM. 143 Germany, which are the principal source. Also found in plant ash, in argols (crude potassium tar- trate), and in niter beds Calcutta niter, KNO.^. Preparation. — The metal is obtained by reduction of its carbonate by means of carbon and high heat in an iron retort and subsequent redistillation. Properties. — It is a silver-white, lustrous metal, soft at ordinary temperature, brittle at 0° C, fusing at 62° C. It distills at a red heat. Potassium has great afilinity for oxygen, and tarnishes immediately when exposed to the air, and frequently ignites. It burns with a peculiar grayish-purple flame. It decomposes water, liberating hydrogen gas. Must be preserved under a hydrocarbon oil, as kerosene. Compounds. — The salts of potassium arc very numerous and very common, many quite similar to the corresponding sodium salt, which can be seen for comparison. There are eighteen compounds of potassium recognized in the U. S. P. Potassium hydro.xid (potassii hydroxidum U. S.P.), KOH. (Potassa U. S. P. 'go); potassium hydrate, caustic potash. Made by the action of slaked lime on potassium carbonate. The solution is decanted, evaporated to dryness, fused and cast into moulds: K2CO3 + CaCOlflj = 2KOH -f CaCOg. Purity, 85%, and not more than 2% of other inorganic substances, with the exception of water. White, hard pencils, very soluble in water and in alcohol. With fats, mixed oils and resins it forms soaps. Uses: caustic and solvent. Preparations: liq. potas- sii hydroxidi, f/f,. 144 PHARMACEUTIC CHEMISTRY. Virnita lime (polassa cum calce), not official. Made by fusing together equal parts of KOH and CaO. Potassium acetate (potassii acetas), KCjHjO,. Purity 98%. A white powder or crystalline masses, saline taste; very deliquescent. Made by decom- posing potassium bicarbonate with acetic acid, filter- ing and evaporating. KHCO3 + CH3COOH = CH3COOK + CCX + H^O. Soluble in 0.4 part water, 2 parts alcohol. Precipi- tates strong solutions of quinine salts; effervesces with spirits of nitrous ether. Alkalin diuretic. Potassium bicarbonate (potassii bicarbonas), KHCO3. Should contain not less than 99% of pure salt. Colorless, transparent crystals or colorless, odorless, granular powder, saline, alkalin taste. Prepared by ])assing CO, in a solution of a carbonate, evaporating and crystallizing. .Antacid. Soluble in 3 parts water, almost insoluble in alcohol. KX'()3 + CO, + H,() = 2KHCO3. Also called "saleratus'' or "baking salt." Potissinm bitarlrate{\)ohx^A\ bitartras), KHC,HjOg. Cream of tartar. Purity, 99'','. Colorless, slightly opa(|ue crystals or white, gritty ])owder. Odorless, with pleasant, ;u idulous taste. Made by purifying ''argot,'' the sediment (le|)()siu-(l during fermenta- tion of wine in barrels. Soluble in 200 parts water, more soluble in s ilutions of borax or boric acid, sparingly soluble in alioliol. \\'ilh hydroxids and carbonates of the alkalis it forms soluble neutral salts. Used as a diuretic and cathartic. As cathar- POTASSIUM COMPOUNDS. I45 tic, it is often prescribed with sulfur and adminis- tered with molasses and water. Impurity: Calcium tartrate; forming white precipitate with ammonium oxalate. Potassium bromid (potassii bromidum U. S. P.), KBr. Purity, 97%. Colorless, in cubical crystals or a granular powder. Odorless, possessing a strong saline taste. Made by treating solution of i)otassium hydroxid with bromin, evaporating and igniting with charcoal. In the reaction both the bromid and bromate are formed. When heated with charcoal and starch, the bromate is deoxidized, CO2 escaping. Thus: (i) 6K0H + 3Br., = sKBr + KBrO., + 3H3O. (2) 2KBr03+ 3C = 2KBr + 6CO2. Potassium carbonate (potassii carbonas U. S. P.), K2CO3. Sal tartar, pearlash. Should contain when thoroughly dried not less than 98% of the pure salt. A white, granular powder, odorless, strongly alkalin taste, very deliquescent. Made by purifying common pearlash by dissolving it in cold water, filtering, evaporating and granulating. Carbonates are decomposed by acids, excepting hydrocyanic. Both potassium and sodium carbonates precipitate salt solutions of nearly all other common metals. Free alkaloids are precipitated from their aqueous salt solution by the carbonates. Lye, potash and "pearlash" are produced when ashes from burnt wood are lixiviated or "leached" (percolated) with water. The percolate is evapo- rated in iron pots, and the impure carbonate is 146 I'HARMACKUTIC (IlKMISTRY. called "pearlash," "potash" or "lye". SoluI)le in i part of water. Poisonous. Potassium chlorate (potassii chloras), KCIO3. Kali chloricum. Purity, 99%. Made by passing chlorin gas into a solution of potassium hydroxid and boiling, according to the following reaction: 6K0H + 3CI2 = 5KCI + 3H2O + KCIO3. Also prepared by reacting on potassium chlorid with calcium hypochlorite solution. Solul)le in 16 parts water. Chlorates are powerful oxidizing agents, incompatible with reducing agents, with which they explode on dry trituration or heating. When tritur- ated with organic substances, as tannic acid, cork or sugar, or with inorganic substances, as sulfur, anti- mony sulfid, phosphorus or other easily oxidizable substances, it conflagrates. Description : Colorless, lustrous prisms or plates or a white granular i)-.)wdcr; odorless; cooling taste. Used as antiseptic, stimu- lant to mucous membrane. Preparations: Trociic, KCIO3 (0.15 gm. in each). Potassium citrate (potassii citras U. S. P.), KaCy- H5O7 4- H.^O. Purity, 999;,. Prepared by neutraliz- ing solutions of citric acid with potassium bicarbo- nate, evaporating and granulating: 3KHC03 + H3C«H507=K3C„H,()7 + 311,0 + 3C().,. Trans])arent crystals or white, granular jjowder, deli- (juescent, odorless, with a cooling taste. Soluble in 0.5 part water, sparingly in alcohol. Incompati- ble with le^d and silver salts, lime water, and quinine solutions. Used as alkalin diuretic. Prep- POTASSIUM COMPOUNDS. 1 47 arations: Potassii citras effervescens, 20%; liquor potassii citras, 8%. In the Pharmacopoeia, 1880, mistura potassii citra- tis was official, known as "neutral mixture." This was a more agreeable preparation to the taste, made by nearly neutralizing lemon-juice with potassium bicarbonate. Potassium cyanid (potassii cyanidum U. S. P.), KCN. "Poisonous prussiate of potash." White, opaque, amorphous pieces or granular powder; odor- less when dry; deliquescent in air, emitting the odor of KCN. Soluble in 2 parts water, sparingly in alcohol. Potassium dichromate (potassii dichromas U. S.P.), K2Cr207, known in the last Pharmacopoeia as " potassii bichromas." Bichromate of potash. Purity, 99%. Description: Large, orange-red, transparent prisms or tabular crystals, odorless, acid, metallic taste. Made by treating potassium chromate with sulfuric acid, evaporating and crystallizing. Thus: 2K2CrO, + H,SO, = K2Cr20, 4- K^SO, + HjO. A powerful oxidizing agent, almost universally in- compatible. Soluble in 9 parts water. Insoluble in alcohol. Used as caustic and antiseptic in pills or capsules, with kaolin as diluent and petrolatum as excipient. Potassium sodium tartrate (potassii et sodii tartras U. S. P.), KNaC^H.Og-f 4H2O. Rochelle salts, Seignettes salts. Colorless, transparent prisms or white powder. Odorless, cooling taste, efflorescent. Purity, 99%. Made by treating solution of potas- sium bitartrate with sodium carbonate. 148 PHARMACEUTIC CHEMISTRY. 2KHC,H,0„ + Na,C03 = 2KNaC,H/)„ + H,0 + CO,. Soluble in 1.2 parts water. Insoluble in akoliol. Incompatible with nearly all acids. Used as hydrc- gogue purgative. Preparations: (Pulv. Efferv. Comp.) Seidlitz powder. Potassium jerrocyanid (potassii ferrocyanidum U. S. P.), K.FeCNg + 3H2O. Yellow prussiate of potash. Large, soft, transparent, yellow, four-sided crystals or prisms. Odorless, with mild, saline taste. Slightly efflorescent. Purity, 99%. Made by treat- ing nitrogenized substances (refuse animal matter, such as hair, hoofs, horns, etc.) with crude potash, with which impure potassium cyanid is formed. This mass is lixiviated and treated with freshly precipitated ferrous carbonate, with which the ferrocvanid is formed. Thus: 6KCN-f-FeC03 = K,Fe(CN)6+K,C03. Soluble in 4 parts water; insoluble in alcohol. Used mainly in the preparation of cyanids. (Potassii ferricyanidum), K3Fe(CN)e, • "Red prussiate of potash. Not oflicial. Employed as reagent for the detection of ferrous salts, with which it gives blue precipitates. Potassium Hypo phosphite (potassii hypophosjyhis U. S. P.), KPH-jO,. Purity, 98%. Should be pre- served in well-stoppered bottles. White, ojiacpie, hexagonal plates or crystalline masses or granular powder. Description: Odorless, ]ningent, saline taste, very dcliciuescent. Made l)y i)recii)itating cal- cium hvp<)i)h<)Si)liitc witli ])(itas>iuni cartionate, POTASSIUM lODID. 149 filtering, evaporating and granulating at a tempera- ture below 100° C. Above this degree of heat, the salt explodes. Explosions have occurred when this salt was triturated or heated with nitrates, chlorates or other oxidizable substances. Solubility: 0.5 part water, 7 of alcohol. Insoluble in ether. Used as expectorant tonic. Preparations: Syr. hypophos- phitum (1.5%), Syr. hypophosphitum comp. (1.75%). CalPH^O,)^ + K2CO3 = 2KPH2O2 + CaCOg. Potassium iodid (potassii iodidum U. S. P.), KI. Made by adding iodin to hot solution of KOH, evaporating to dryness, mixing with charcoal or starch, heating to redness, dissolving in water and crystallizing. U) 3I2 + 6K0H = 5KI + KIO3 + 3H2O. (2) 2KIO3 + 3C = 2KI + 3CO2. The charcoal or starch is added to convert the oxy- gen into CO,, and thus reduce the iodate and convert it into an iodid. Description: Colorless, transparent, translucent or opaque, white cubical crystals or a white granular salt, with faint, iodin-like odor, pung- ent, saline, afterward bitter taste. Purity, 99%. Slightly deliquescent in moist air. The commercial salt is crystallized from an alkalin solution, making it more stable, and occurs in white crystals having an alkalin reaction, owing to the presence of potassium carbonate. The chemically-pure salt should have a neutral reaction. Soluble in 0.7 part water, 12 parts alcohol, 2.5 parts glycerin. Incompatible with lead and silver salts. Alterative. Preparation: Ung. Pot. lodidi (10%). 150 PHARMACEUTK- CHEMISTRY. Test to Detect lodate. — Add gelatinized starch and dilute H2SO4. A blue color will appear. Potassium nitrate (potassii nitras U.S.P.), KNO3. Saltpeter, niter, Calcutta niter. Purity, 99%. Found native in India. Description: Colorless, transparent crystals or white, crystalline powder. Odorless, with a cooling, saline taste. Soluble in 3.6 parts water, sparingly in alcohol. Obtained by lixiviating the earth from the niter beds of India and filtering, evaporating and crystallizing. Used as a diuretic. Potassium permanganate (potassii permanganas U. S. P.), KMnO^. Purity, 99%. Comes in slender, monoclinic prisms of a dark purple color and a blue metallic luster by reflected light. Odorless; taste at first sweet, afterward disagreeable and astringent. Used as antiseptic, deodorant, emmenagoguc. Ad- ministered in pill form with kaolin and petrolatum. Made by boiling a solution of potassium manganate with water. sK^MnO, + 2H20 = 2KMnO,+ MnO^ + 4KOH. Soluble in 15 parts of water; it decomposes in con- tact with alcohol or glycerin. It is a powerful oxidiz- ing agent, very incompatible with reducing agents, with some of which it explodes on dry trituration. It should not be brought in contact with organic substances. Potassium sulfate (potassii sulphas U. S. P.), K2SO4. Purity, 99%. Hard, colorless, transparent crystals or a white powder, odorless, having a some- what bitter, saline taste. Soluble in 9 parts water, insoluble in alcohol. Used as cathartic. Made by SODIUM. 151 purifying residue from nitric acid manufacture. Native as kainite. Found in the Stassfurt salt beds as a double sulfate of potassium and magnesium. Made directly by decomposing common niter with H^SO^thus: 2KNO3 + H,SO, = K2SO, + 2HNO3. Among the frequently used compounds of potash, is potassa sidphurata — sulfurated potash (liver of sulfur). Made by heating together sublimed sulfur, I, and potassium carbonate, 2. SODIUM, Na, 23. Sources: (i) Sea water; (2) mineral springs; (3) cryolite, the double fluorid of sodium and aluminum; (4) borax lakes of California; (5) Chili niter. The salts of sodium are cheaper and more frequently used than those of potassium. As a rule, they are also more soluble. Sodium hydroxid (sodii hydroxidum), NaOH. Caustic soda, sodium hydrate. Known in the last U. S. P. as "soda." Prepared from slaked lime and sodium carbonate. The solution is decanted and evaporated. The crude salt is largely contaminated with carbonate and called "soda ash." Na2C03 + Ca(OH)3 = 2NaOH + CaCOj. Purity, 9o^/(, and not more than 2% of other inor- ganic substances. Description: Dry, white flakes, fused masses or sticks. Soluble in i part water. Very soluble in alcohol. With salts it forms acids and water. Preparations: Liq. sodii hydroxidi (5%). Antacid. The chemically-pure salt is prepared by 152 PHAKMAi EUTIC (IIEMISTKY. oxidizing metallic sodium with distilled water and evaporating. Sodium acetate (sodii acetas U.S. P.), CHgCOONa -f3H20. Description: Large, colorless, trans- parent, monoclinic prisms or granular powder, ef- florescent, odorless, bitter taste, alkalin reaction. Purity, 99.5%. Made by decomposing sodium carbonate with acetic acid. 2CH3COOH + Na^COg = 2('H3COOXa -h H2O + CO.. Sodium acetate is soluble in 1 part water, 23 parts alcohol. Used as diuretic. Sodium arsenate (sodii arsenas), XajHAsO^ + 7H2O. Purity, 98% of pure disodium-orthoarsenate. Description: Colorless, transparent crystals, having a mild, alkalin taste. Very poisonous; soluble in 1.2 parts water, sparingly in alcohol; precipitated by tannic acid. Oxidizes hypophosphites, sulfites and iodids. Precipitates alkaloidal salts. Used as tonic, alterative, hematinic. Made l)y heating together arsenous acid, sodium nitrate and carbonate, which form sodium pyroarsenate. The pyroarsenate is then converted into the orthoarsenate by dissolving it in water, fdtering and crystallizing. Thus: Na.As^Oy + 15H2O = 2Na.,HAsO, + 7^,0. Exsiccated sodium arsenate (sodii arsenas exsic- catus) should contain not less than 98% of anhyd- rous disodium-orthoarsenate. Prepared by drying the crystals at a temperature between 40 and 50° C. until disintegrated, then at 150° C. until they cease to lose weight- Description: An amorphous white soniiur coMi'oiiNDS. .153 ])()wder, odorless, and having a mild, alkalin taste. Preparations: Liq. sodii arsenatis (i'-/,). . Sodium Benzoate (sodii l)enzoas), CgH^COONa. IHiritv, 9(/','. Description: A white, amorphous, granular or crystalline powder; odorless with a sweetish, astringent taste. Soluble in 1.6 parts water, 43 parts alcohol. Stronger acids precipitate it from its solution. It precipitates also salts of silver, mercury and lead; precipitates pinkish fer- ric benzoate from the neutral chlorid and solutions of cjuinine bisulfate. Used as antiseptic, expectorant, diuretic. Made by decomposing sodium carbonate with benzoic acid. 2C6H5COOH + Na2C03 = 2C6H5COONa + CO2 + H.,0. Sodium bicarbonate (sodii bicarbonas), NaHCOg. Purity, 99%. Description: A white, opaque, powder, odorless with a cooling, mildly alkalin taste. Also called "baking soda" and soda saleratus. Made by washing commercial NaHCOg with HjO. Solvay's process : NaCl + NH3 + CO2 + H2O = NaHCOg +NH,C1. Preparation: Troch. sodii bicarb. Solubility: 12 parts water. Sodium bisulfite (sodii bisulphis), NaHSOg. Purity, 90%. Description : Opaque, prismatic crystals or granular powder with odor of SOj and a disagreeable sulfurous taste. Exposed to the air, it is gradually oxidized to a sulfate. Made by saturating sodium carbonate with sulfurous acid. NaXO,, + 2H.,S0, = 2NaHS0, + CO., + U.O. 154 PHARMACEUTIC CHEMISTRY. Soluble in 3.5 parts water, 70 i)arts alcoliol. Incom- patible with acids. Antiseptic. Sodium borate (sodii boras), NajB^O^ + loH^O. Borax. Purity not less than 99% of pure sodium tetraborate (orthoborate). Description: Colorless crystals or a white powder, having a sweetish, alkalin taste. Soluble in 20.4 parts water, i part glycerin; insoluble in alcohol. Incompatible with neutral solutions of many metals. Also with alum, calcium chlorid and barium chlorid. With mineral acids, boric acid is precipitated out. . It precipitates alkaloidal salts; glycerin, glucose or honey liberate boric acid from solutions of borax, rendering them incompatible with carbonates. Mild antiseptic. Made by i)urifying the neutral salts found as a crystalline dej)osit in the blue mud of Clear Lake, California. It is alst) called timal. Found in Tuscany as crude boric acid. Sodium bromid (sodii bromiduni U. S. P.), NaBr. Purity, when dried, 97%. Description : Colorless or white cubical crystals or granular powder, saline, with bitter taste. Absorbs water from the air w ithout deliquescing. Soluble in 1.7 parts water, 12.5 parts alcohol. Incompatible with alkaloidal salt solutions. Made by treating ferrous bromid with sodium car- bonate, liltering, evaporating and crystallizing. FeBr, + Na.CO., = 2NaBr + FeCOj. Used as sedative nervine. Monohydratcd sodium carbonate (sodii carbt nas mcmohydratus U. S. P.), Na,CC), + HjO. Purity, 85% of pure anhydrous salt, corresponding to 99.5% SODIUM CARBONATE. 1 55 of the crystallized salt. Description: Monohy- drated sodium carbonate is a white, crystalline, granular powder, odorless, with strong alkalin taste. It effloresces at 50 C, and at 100° C. loses its water of crystallization (14.5%). Leblanc's process: Com- mon salt is converted into the carbonate by two steps: ist step: into the sulfate: 2NaCl + H2SO,=Na2SO, +2HCI. 2d step: the sulfate with charcoal into carbonate: Na2SO, + C, + CaC03 = Na2C03 + CaS + 4CO. This mass is now digested in warm water which dis- solves out the alkali, leaving behind the insoluble "soda waste," which latter is used in the manufacture of sodium hvposulfite. The above solution is evaporated to dryness and the mass calcined with sawdust, which converts the alkali, owing to its COj, fully into carbonate. This is redissolved, filtered and evaporated. This "soda ash" contains about 50% of sodium carbonate. The CryoHte process is used in the United States: Cryolite, a double fluorid of alumi- num and sodium (Al2Fg.6NaF) is heated with chalk. The mass is leached by Hxiviation. The alumina becomes insoluble and is deposited. The liquid is filtered, purified and crystallized. In the U. S. P. '90, sodii carhonas was official, a salt which contained ten molecules of water of crystallization. This has been supplanted with the monohydrated sodium car- bonate. Sodii carbonas exsiccatus (dried) was also official. Used as antacid. Solubility: 2.9 parts water, 8 parts glycerin, insoluble in alcohol and ether. 156 PHARMACKUTIC CHEMISTRY. Sodium chlorate (sodii chloras U. S. P.), NaClOj. Purity, 99*^0- Colorless, transparent crystals or a crystalline powder; odorless, cooling saline taste. Soluble in i part water, 5 parts glycerin, 100 j^arts alcohol. Caution: Sodium chlorate is explosive when heated or triturated with organic substances or oxidizable bodies. Made by the Witt stein process, from sodium carbonate and tartaric acid. Na2C03 + 2H,C,H,0,= 2NaHC,H,06+C02 + H.,0. Then the bitartrate is added to potassium chlorate. NaHC.H.Og + KCIO3 = NaClO., + KHC^H^Og. Note. — When this salt is prescribed, under no cir- cumstances should sodium chlorid be dispensed. Sodium chlorid (sodii chloridum), NaCl. Sal communis, sal culinaris, common salt. Purity, when dried, 99%. Description: colorless, transparent cubical crystals or a white, crystalline powder. Permanent in dry air, pure saline taste, obtained by evaporating sea-water and the brine from salt wells and springs. When magnesium chlorid is present as impurity, the salt is very deliquescent. Sodium citrate (sodii citras), 2Na3C„H.-C)7 -{- 11H2O. Purity, 97%. A white, odorless, granular powder, having a cooling, saline taste. Effloresces slowly. Prepared by adding sodium carbonate to a solution of citric acid until efTervescence ceases, evaporating and granulating. Soluble in i.i parts water, slightly in alcohol. Diuretic. Sodium hypophosphite (sodii hy])o])ln)Si)his\ NaPH,(X-|-ir,(). Purity, 98C; . Description: ^m:i\\. SODIUM COMPOUNDS. 157 colorless, transparent plates of pearly luster or white granular powder. Odorless, bitterish, saline taste. Very deliquescent. Made by double decomposition between calcium hypophosphite and sodium car- bonate. (See reaction under potassium hypophos- phite.) The salt explodes with violence during evaporation which should, therefore, be performed below 100° — better at 85° C. Soluble in i part water, 25 parts alcohol; insoluble in ether. Used as tonic. Preparations: Syr. hypophosphitum (1.5%) and syr. hypophos. comp. (1.75%). Sodium iodid (sodii iodidum), Nal. Purity, 98%. Colorless, cubical crystals or crystalline powder. Description: Odorless, with saline, bitterish taste. Soluble in 0.5 part water, 3 parts alcohol. In moist air the salt decomposes, assuming a brown tint. Alterative. Preparation: Fel. + Na2C03 = 2NaI + FeCO,. Insoluble iron carbonate is filtered off. The solution is then evaporated and crystallized. Sodium nitrate (sodii nitras), NaNOg. Chili saltpeter, cubic niter. Purity, 99%. Found native in Chili and Peru. Obtained by lixiviation, evapo- ration and crystallization. Colorless, transparent, rhombohedral crystals, odorless, cooling, saline, bitterish taste. Hygroscopic. Soluble in i.i parts water and 100 parts alcohol. Diuretic. This salt constittites the cheapest source for obtaining nitrates. Sodium nitrite (sodii nitris), NaNOj. Should contain not less than go% of the pure salt. Descrip- 158 I'llAR.MACKlTIC CHEMISTRY. lion: White, opaque fused masses or pencils or transparent, hexagonal crystals. Odorless, mild saline taste. Very deliquescent; gradually oxidizes and is converted into sodium nitrate and becomes unfit for use. Soluble in 1.4 parts water, sHghtly in alcohol. Incompatible with hypophosphites, sul- fites, iodids, ammonium bromid. It reduces chlor- ates, permanganates, chromates, hydrogen dioxid, mercurous and mercuric salts. Vasodilator. Sodium phenol -sulfonate (sodii phenol-sulphonas), NaCgHjSO^ -I- H2O. Purity, 99% of pure sodium paraphenol-sulfonate. Description: Colorless, trans- parent, rhombic prisms, made by dissolving sodium carbonate in phenol-sulfuric acid. Soluble in 4.8 parts water, 130 parts alcohol. Antiseptic. Sodium phosphate (sodii phosphas), Na^HPO^ 4-12H2O. Purity, in the uneffloresced condition, 99% of pure disodium-orthophosphate. Description : Large, colorless prisms or granular salt. Odorless, cooling, saline taste. Crystals effloresce in the air, losing 5 molecules (25%) of their water of crystal- lization. Cholagogue. Soluble in 5.5 parts water. The salt contains 60.3% of water of crystallization. It precipitates nearly all other metals, some of the alkaloidal salts, and liquefies when triturated with lead acetate, phenol, chloral hydrate or salicylic acid. Prepared by dissolving calcined bones (neutral calcium phosphate) in concentrated sulfuric acid. Acid calcium phosphate is formed. By boiling this solution with sodium carbonate the phosphoric acid is SODIUM COMPOUNDS. I 59 completely saturated and the calcium is thrown down as insoluble calcium sulfate. (1) Ca3(PO,)2 + 2H2SO, = CaH,(PO,)2 + 2CaSO,. (2) CaH,(P0,)2 + Na^COg = Na,HPO, + CaHPO, +H,0+ CO.,. The calcium phosphate is separated by filtration and the filtrate evaporated and crystallized. Exsiccated sodium phosphate (sodii phosphas exsiccatus). Purity, 99% of pure anhydrous salt. Description: A white powder which absorbs moisture readily. Made by allowing crystalline sodium phosphate to effloresce for several days in warm air at between 25 to 30° C, then drying in an oven at 100° C. until constant weight. (Sodii phosphas effervescens) effervescent sodium phosphate is made from the exsiccated sodium phos- jjhate — 2o^( . Sodium pyrophosphate (sodii pyrophosphas), Na^PjO^ + 10H2O. Purity, 99%. Description: Colorless, transparent prisms or crystalline powder. Odorless, with cooling, feebly alkalin taste. Slightly efflorescent. Made by heating sodium phosphate to redness, dissolving and crystallizing. Soluble in 1 1.5 parts water; insoluble in alcohol. It precipi- tates solutions of metallic salts. Used in the prepa- ration of ferric pyrophosphate. Sodium saKcylate (sodii salicylas) CgH^(OH)- COONa. Purity, 99.5%. Description: White, microcrystalline powder or scales or an amorphous, colorless powder, having not more than a faint, pink tinge. Odorless, sweetish, saline taste. Sol- l6o PHARMACEUTIC CHEMISTRY. uhlc in 0.8 part water, 5.5 i)arts alcohol, also in glycerin. Antiseptic, cholagogue, antirheumatic. 2C6H,(OH)COQH + Na.,C03 = 2CeH,( OH)CQONa I U Q I CO sodium salicylate For internal administration only the salt i;repari(l from oil of wintergreen should be dispensed. Sodium suljate (sodii sulphas), NajSO^ + ioH._,(,). Glauber's salt. Purity, in the uneffloresced con- dition, 99%. Description: Large, colorless, trans-, parent prisms or granular crystals. (Morless, saline, bitter taste. The salt effloresces rapidly in the air and quickly loses all of its water of crystallization. Made bv decomposing common salt with sulfuric acid. Soluble in 2.8 parts water, also in glycerin; insoluble in alcohol. When heated.it dissolves in its own water of crystallization. Incompatible witii metallic chlorids. Used as hydragogue cathartic. Sodium sulfite (sodii sulphis), Na^SOj -1- 7H,(). Purity, in the uneffloresced and air-dried condition, 96%. Description: Colorless, transparent, mono- clinic prisms, odorless, cooling, saline and sulfurous taste, effloresces on exposure, and slowly oxidizes to a sulfate. Soluble in 2 parts water, sparingly in alcohol. It is decomposed by acids. Used as antiseptic. The salt is made by passing SO, gas into a solution of sodium carbonate, thus forming sodium bisulfite, mixing this with an- equal weight of sodium carbonate, neutral sulfite is formed. Na,CC)., + SO, = Na,SO, -f CO... Sodium thiosuljate (sodii thiosulphas), Na,S._,0;, -(- qli.O (sodii hyp()suli)his U. S. P. \)o) "hyposul- . AMMONIUM. l6l fite." Purity, 98%. Description: Colorless, trans- parent, monoclinic prisms. Permanent below 33° C, but efflorescent above that temperature. Deliquescent in moist air; odorless; cooling, somewhat bitter taste, neutral reaction. Made by decomposing calcium thiosulfate with sodium sulfate. Soluble in 0.35 part water, slightly in oil of turpentine; insoluble in alco- hol. Incompatible with acids; precipitates barium, silver, lead and mercurous salts from aqueous solu- tions. In acid solution it is a powerful reducer, incompatible with oxidizing agents. The tritura- tion of it with strong oxidizing substances results in explosion. Antiseptic. Used in photography. CaS.,03 + Na^SO, = Na2S303 + CaSO,. AMMONIUM, NHj, 18. Source. — Coal-gas liquor, which is the by-product in the manufacture of boneblack. Ammonium (NH^) is a compound of nitrogen and hydrogen. It is not found free and has never been isolated. It is a radical, also called a "quassi metal" and classed with the alkalis for convenience only. Ammonia (NH3) is a saturated compound capable of existing in the free state. It occurs in the atmosphere, in natural waters and in the earth. Difference between the salts of the alkalis and ammonium is but one: all ammonium salts are volatile at a moderate tem- perature, the other alkali salts are not. Remember the difference between (NH3), a saturated com- pound, and ammonium, a radical (NHJ. In ammonia the nitrogen is a triad; in ammonium it is a pentad. l62 PHARMACEUTIC CllKMlS TRY. Compounds: Ammonium benzoale (ammonii benzoas), XH^C";- H5O2. Purity, 98%. Description: Thin, white, Hminar crystals or powder; odorless; saline, l)iiter, slightly acrid taste. Soluble in 10.5 parts water, 25 parts alcohol. Used as antiseptic, expectorant, diuretic. Made by dissolving benzoic acid in ammonia water. HC7H5O2 + NH,(OH) = NH.C^HgO., + H.,(). Ammonium bromid (ammonii bromidum), NH^Br. Purity, qfi{. Should be preserved in well-stoppered bottles. Colorless, prismatic crystals or crystalline powder; odorless, with pungent, salty taste. Soluble in 1.2 parts water; 12.5 parts alcohol. Sedative nervine. Made by Pile's process of adding ammonia water to bromine water: 6Br + 8NH3 = 6NH,Br + N,. Ammonium carbonate (ammonii carbonas), C^Hji- N3O5. Should contain not less than 97% of a mixture of ammonium bicarbonate and ammonium carbamate, and should yield not less than 31.58% of ammonia gas. For dispensing purposes, only the translucent portions should be used. The opaque, friable white powder or porous lumps on the outside are the inert ammonium bicarbonate, and should be rejected. Also known as "baker's ammonia," sal volatile, hartshorn. Description: White, hard, translucent masses, with strong ammoniacal odor and a sharp saline taste. Changes to white powder on ex])osure to the air. Soluble in 4 jiarts water; alcohol dis- solves the carbamate, but not the liicarbonate. AMMONIUM COMPOUNDS. 1 63 When the official salt is dissolved in water containing ammonia gas, it is converted into the true carbonate, the formula for which is (NH4)2C03, according to the following reactions: From the carbamate: {a) NH^.NH^.COg + H^O = (NHJ^COg. From the bicarbonate : (h) NH.HCOg 4- NH3 = (NHJXO3. The salt is made by subliming a mixture of ammonium sulfate and calcium carbonate: 2(NH,)2SO, + 2CaC03 = NH,HC03.NH,NH,CO, + H2O + NH3 + 2CaSO,. Used as a reflex stimulant, carminative, expectorant. Preparations : Liquor ammonii acetatis (5%) . Incom-. patible with mercuric chlorid, calomel, copper and silver salts, alkaloidal salts. It should be dispensed with care with syrups of squills, ipecac and of citric acid or any syrup containing an acid. Ammonium chlorid (ammonii chloridum), NH^Cl. Sal ammoniac, muriate of ammonia, battery ammonia. Purity, 99.5%. Description: White crystalline pow- der, permanent, odorless, cooling, saline taste, with a neutral reaction. Soluble in 2 parts water, 50 parts alcohol and 5 parts glycerin, and i part boiling water. Made by subliming a mixture of ammonium sulfate (a by-product from gas manufacture) and sodium chlorid. (NHJ2SO, + 2NaCl = Na^SO, + 2NH,C1. Incompatible with alkali hydrates or carbonates or the hydroxids of the earthy metals which liberate NH3 gas from it. With chlorin gas explosive 164 I'HAKMACEUTIC CHEMISTRN . nitrogen chlurid may he furnifd. Ivxpectorant. hepatic stimuhmt. Preparations: Troeh. amnionii ( hioricii (o.i gni. each). Ammonium iodid (ammonii iodidum), NH^l. Purity, 97%. When deeply colored, the salt should not he dispensed. It may be deprived of free iodin hy adding to its concentrated solution ammonium sultid sufficient to decolorize it, fdtering, evaporat- ing on water-hath to dryness. Description: Minute, cubical crystals or white, granular powder; when colorless without odor, but emitting odor of iodin when colored. Sharp, saline taste, very hygroscopic. Made by mixing solutions of potassium iodid and ammonium sulfate. 2KI + (NH,),S(), - 2NHJ + K.,SO,. Soluble in 0.6 part water, 9 parts alcohol. Alterative. Ammonium salicylate (ammonii saHcylas), NHiC^- H.O,,. Purity, 98^,. Should l)c protected from heat and light and preserved in well-stoppered l)ott!es. Description: Colorless, lustrous crystals or plates or crystalline powder. Odorless, with a slightly saline, bitter taste, and a sweetish after- taste. Made by neutralizing ammonia water with .salicylic acid, evaporating and crystallizing. Soluble in 0.9 part water, 2.1, parts alcohol. Used as anti- septic, cholagogue and antirheumatic. Ammonium valerate (ammonii valeras), NH4C.:i- H„( ).,. (Ammonii valerianas U. S. P. 'go.') Descrip- tion: Colorless or white, ([uadrangular plates, emitting the odor of valeric acid, with a sharp, sweetish taste; deliquescent in moist air. Purity, AMMONIUM COMPOUNDS. 1 65 (j8'\ . Should hf preserved in stoppered bo.ttles. Made by passing ammonia gas into valerianic acid. The^alt, as found in commerce, is generally the acid salt and should be neutralized with ammonia when used in solution for making preparations like the various elixirs. Very soluble in water and in alcohol ; also soluble in ether. Incompatible with hydroxids and carbonates and sulfuric acid. Antispasmodic. It should be noted that Ammonia combines with acids and the halogens to form corresponding salts. Ammonium iodid is readily decomposed into nitrogen iodid, which is very explosive. Am- monia water precipitates solutions of mercury, lead, silver, copper, zinc, bismuth, iron, manganese, aluminum, chromium, antimonx'. With mercurous chlorid it forms a black precipitate. It also precijii- tates tartaric and picric acid solutions. With the latter acid it forms the powerfully explosive ammo- nium picrate. Ammonia precipitates nearly all alkaloids from their salt solutions. It decomposes chloral into chloroform and a formate. When boiled with solutions of formaldehyd, hexamethy- lenamin (urotropin) forms. Permanganates oxidize it to nitrate. Reactions: with phenol, blue color is slowly developed; with gallic acid, yellow to reddish - brown coloration ; with thymol, green color is formed. Preparations: Aqua ammoniae (lo*^,-), sp. gr., 0.958; aqua ammoniae fortior (28%), sp. gr., 0.897; spiritus ammoniae (10%); spir. ammoniae aromaticus (am- monia water, 9%; lin. ammoniac (ammonia water, 35%)- l66 PHARMAnaXIC ciiemistrv. MAGNESIUM, Mg, 24. Sp., gr., 1.75. Occurrence. — Very abundant metal, not found free in nature. Many of its mineral compounds, as talc, asbestos, soapstone, magnesite, dolomite, kie- serite and meerschaum, are very familiar. .\s a sulfate, it is found in many saline springs, as the Epsom, of England, and as chlorid in sea-water. The silver-white metal magnesium, in the form of a ribbon or wire, when held in a flame burns with an in- tensely active flame, producing a bulky, white i)re- cipitate. Four magnesium salts are official. Magnesium carbonate (magnesii carbonas U. S. P.), (MgC03),.Mg(OH)2 + 5H,0. When ignited, it should yield 40% of residue, of which 96% should be pure magnesium oxid. Light, white friable masses or a bulky powder; odorless with an earthy taste; per- manent Made by double decomposition between magnesium sulfate and sodium carbonate. When the solutions are made in boiling hot water, the heavy carbonate results. When the cold solutions are em- ployed the light carbonate is the product. Insoluble in water and alcohol; dissolves in dilute acids with effervescence. Antacid, laxative. Preparations: Liq. magnesii citratis. SMgSO, -f 5Na.,CO, -f H.,0 = 4MgC03.Mg(OH), + SNa.SO, -h CO,. Magnesium oxid (magnesii oxidum U.S. P.), MgO Magnesia (magnesia U. S. P. '90), calcined magne- sia, light magnesia, magnesia levis). Purity: after ignition, it should }ield 96% of pure magnesium oxid, a white, ver\- l)ulk\- and vcrx- luu' powder. MAGNESIUM. 1 67 slowlv al)S()rl)ing moisture and CO. from the air. Odorless, with earthy taste. Made by calcining light magnesium carbonate. (MgC03),.Mg(OH)2 + 5H,0 = sMgO + 4CO, + 6H2O. Almost insoluble in water; dissolves in acids. With 15 times its weight of water it gelatinizes forming a hydrate. Antacid. Heavy magnesium oxid (magnesii oxidum ponder- osum U. S.P.), MgO (magnesia ponderosa U. S. P. '90), heavy magnesia. A white, dense and very fine powder which should conform to the reactions and tests given under magnesii oxidum. It differs from the latter in not readily uniting with water to form a gelatinous hydroxid. The salt is similar to the light magnesia, except in possessing only one-fourth the bulk which facilitates its administration. It is prepared by calcining heavy magnesium carbonate which is produced by precipitating a hot, concen- trated solution of magnesium sulfate with sodium carbonate. The salt is soluble in acids; insoluble in water and alcohol. Used as antacid and laxative. Magnesium sulfate (magnesii sulphas), MgSO^ -(- 7H2O, commonly called Epsom salt, after the English spring in which it is found. It is also manufactured from the mineral kieserite, which is an impure sulfate containing but one molecule of water of crystallization. Four-sided prisms or acicular crystals. Odorless, cooling, saline, bitter taste. Slowlv efflorescent in the air. Soluble in 0.85 part l68 PlfAKMACKl'TIC CHEMISTRY. water and in 0.13 parts hot water; insoluble in alcohol. Used for the jireparation of the carbtinate. Soluble magnesium salts are precipitated by soluble hydroxids and carbonates (except ammonium salts) and by phosphates, arsenates, sulfites, oxalates and tartrates; also incompatible with the chlorids of the heavy metals. Used as hydragogue purgative. Preparations: Magnesii sulphas effervescens (5o9c). Tests. — The follow-ing method may be employed to detect the metals of this group. To a portion of the solution add sodium hydroxid and heat in a test- tube. The formation of ammonia, which may be detected by its odor or action on test papers or white fumes with hydrochloric acid prove the presence of a mmonium compounds. To a second portion add ammonium chlorid, am- monium hydroxid and sodium phosphate. A white, crystalline precipitate of ammonium magnesium phosphate proves the presence of magnesium. Evaporate a third and quite a large portion of the original solution to dryness and ignite sufficiently to volatilize all ammonium salts. Dissolve the resi- due in a small amount of water, add a drop of hydrochloric acid. Dip a clean platinum wire formed into a small loop into the solution and place it in the Bunsen flame. An intense yelloiv color indi- cates sodium; a lilac or grayish-purple color shows potassium. Examined through a polariscope, potas- sium is indicated by a crimson line. Add t<^ the solution of the above residue a few drops of platinic (■lil(ui(l solution: A yclhnc precipitate of potassium PERIODIC LAW. 169 platino-chlorid confirms potassium. Lithium in solution imparts a brilliant carmine-red to the fiamc. Disodium phosphate boiled with the lithium solution produces an insoluble lithium phosphate. This pre- cipitation is complete when sodium hvdroxid is present. CLASSIFICATION OF THE ELEMENTS ACCORD- ING TO "PERIODIC LAW." As has already been noticed, the nonmetallic elements seem to arrange themselves into groups or families. The halogens, for example, obviously form a group of closely related elements; and it is found that in such a group there is a more or less regular increase in the atomic weights. Thus, the atomic weight of bromin (80) is nearly the mean be- tween the atomic weights of chlorin and iodin. 2 Carbon and silicon, oxygen and sulfur, nitrogen and phosphorus are similarily related. Among the metals, we have the group lithium, sodium and potassium; the continuation of the nitrogen family — arsenic, antimony and bismuth, etc. John New- lands (1864) pointed out that, if the elements were arranged in the numerical order of their atomic weights, there was a recurrence of similarity in chemical and physical properties at every eighth element. He called this "The Law of Octaves." [70 PlIARMAri-:UTIC CHEMISTRY. NEWLAND'S CLASSIFICATION OF THE ELEMENTS. Atomic weigh t Atomic weight Lithium, 7 Sodium, 23 Berylh'um, 9 ^Lagnesium, 24 Boron, II Aluminum, 27 Carbon, 12 Silicon, 28 Nitrogen, 14 Phosphorus, 31 Oxygen, 16 Sulfur, ?,2 Fluorin 19 Chlorin, 35-5 About five years a fterw arc] s this idea was worked out more fully by Mendelejeff, who published a table of the elements arranged according to his "Periodic Law," as represented on page 173. The following points should be noticed: (a) After the first two octaves (lithium to chlorin), the resemblance is most marked between alternate rather than between consecutive octaves; thus, tak- ing the second vertical column, magnesium, zinc and cadmium form a natural group, and the other alter- nate octaves, calcium, strontium and barium, form a second natural group. {h) After manganese, a triplet of metals occurs — iron, nickel and cobalt — forming a sort of supple- mentary eighth vertical column; the other triplets are ruthenium, rhodium and palladium, and osmium, ir'dium and platinum. The atomic weights in each of these triplets are close together; thus, Fe, 56; Co, 59; Ni, 58.3. All these metals have high melting- points. PERIODIC LAW. 171 (c) The valences of the elements may he said to in- crease as we pass from the first to the seventh column ; thus: sodium is a monad; magnesium, a dyad; alumi- num, a triad; carbon, a tetrad; nitrogen, a pentad; sulfur, a hexad; manganese, a heptad; the same fact is indicated by the formulas of the oxids at the top of the table. On the other hand, the compounds with hydi-ogen show a diminishing number of atoms of hydrogen in the molecule as we pass from left to right; thus, CH„ NH3, OH,, CIH. Outside the great theoretical interest of this classification, it is of a practical use in several ways: (i) As a check on the atomic weights; thus, tel- lurium is an element which closely resembles selen- ium and sulfur; its old atomic weight was 128, which would place it after iodin in a group to which it was obviously not related; recent determinations have reduced the number to 127, and it seems extremely probable that it has not been obtained perfectly pure. The atomic weight of indium is 38, and its atomic weight was at one time believed to be 38 X 2 = 76, but as there is no space for an element between arsenic and selenium, it was suggested that its atomic weight must be 38 X 3 = 114, which would place it in the column under aluminum. This number was actually confirmed by determining its specific heat. (2) The classification enables us to prophesy the existence and properties, physical and chemical, of undiscovered elements; thus, in columns III and IV, when the table was first published the elements gallium (Ga) and germanium (Ge) were unknown, 172 PllARMACKCTIC CHEMISTRY. Init by t'oniparinj^ ihc- proijcrlics of uluminum and in- dium in one case and of silicon and tin in the other, an accurate forecast of all the chief properties of these elements was made and completely verified when the elements were isolated. There seems to he some difficulty in finding satisfactory jjlaces for the recent elements, argon, helium, neon, etc. 17: > ^ 1 q Fe 56. Co 50. Ni 59 Ru 102. Rh 103. Pd 106 Os 191. Ir 193. Pt 105 > 1 ^-!i s-i 111 ,:s=^-. Ill > > 1 ^ t^f^ 1 1 - 1 S " 1 ^ 1 ^ i " "^ ^ - 1 rt 1 1 > ' U H N U ' ' 1 ' m c)^ >- hJ >^ H . q ■ 1 f N SI it^'i ' pq U c« m ' 3 <^ 3 be 3 , CHAPTER XVII. THE RARE METALS. These metals are of such rarity or of so little \aluc in pharmacy, as to be deemed scarcely worthy of a place in the discussion of the several groups. I. The following are the rare metals of the hydro- chloric acid group, thallium and tungsten. The group reagent precipitates them as thallous chlorid and tungstic acid. THALLIUM, Th, 204, resembles lead in many ways and the alkali metals in some others. It is precipitated as chlorid, but this chlorid readily dis- solves in sulfuric acid, forming soluble thallous suljate. Thallium compounds impart a brilliant green to the ^amc. TUNGSTEN, W, 184. The most commonly met with comixnmd of tungsten is sodium tungstate, which is one of several compounds with sodium. Sodium metatungstate is used to render fabrics uninflammable. Tungsten compounds are characterized by the blue color given %vhen metallic zinc is added to its solution and the solution strongly acidified icith hydrochloric acid. The rare metals oj group II or the hydrogen sul- fid group. I. GOLD, .\u, i()7, and PLATINUM, Tt, 194 These metals are really not rare metals, since they are so well known in a general wa\\ but it is not ollen 174 RARE METALS. 175 that the pharmacy student is called upon to consider compounds containing them. Usually they are met with only as alloys. These metals are insoluble in acids, except the nitrohydrochloric which yields their chlorids. Because of their solubility in this acid it received the name "aqua regia" (kingwater). These metals together with silver and mercury are classed as the "noble metals." But few simple salts are known and these are characterized by the ease with which they are reduced to the metallic state. The chlorids of these metals are precipitated by hydrogen sultid or ammonium sulfid, forming sulfids; on boiling the solution the gold comes down in the metallic state. Both gold and platinum form double salts with the alkalin chlorids; thus NaCl- AuClg; NaClPtCl,. Stannous chlorid with a gold solution gives a reddish-brown to purple color or precipitate, known as the "purple of Cassius." II. Four rare elements — Iridium, telluriuw, sele- nium. a.nd molybdenum form sulfids with the group reagent H^S. They are soluble in ammonium sulfid, hence belong to the arsenic division. IRIDIUM, Ir, 193. 1, differs from platinum in not being soluble in aqua regia. In general it resembles platinum. TELLURIUM, Te, 25 (i) and SELENIUM, Se, 78.8, are on the border-line between nonmetals and metals. They so closely resemble sulfur, as to be classed with the sulfur group. MOLYBDENUM, Mo, 96, is usually met with as the ammonium molybdate, (NHJ2M0O4, and is mostly i>6 PIIAKMACEUTH: CHEMISTRY iiM'd to ])ri'(ij)it;it(.' phosphorus, with which it forms the yellow, insoluble ammonium phosphomolvbdate. Ruthenium, Ru, 101.6; Rhodium, Rh, 103; Pal- ladium, Pd, 106.5, ^^^ Osmium, Os, 190.8. These four elements belong to the platinum group — their sulfids are insoluble in ammonium sulfid. The first two are seldom met with, palladium and osmium more frequently. Osmium, forming osmic acid, is used in the preparation of microscopic sections of animal tissues. This compound is really a tetroxid, OsO^, or an anhydrid. The rare elements of the ammonium sulfid group may be divided for con- venience into five classes, in accordance with the form in which each is precipitated. Taljulatcd thus: II. III. IV. V. (a) Beryllium Be, 9 Be(OH). (n) Siandium Sc, 43.9 .Sr(OH), (b) V ttrium Y, 89 . I V(OH)3 (r) Ylt rhium Vb, 173 I Yb(OH)3 I (d) j Cerium Ce, 133 I Ce(OH)3 I (e) Lanthanum I La, 138.2 La(OH)3 (a) Zirconium Zr, 90 . 4 I Zr(OH)4 (b) Thorium Th, 232 Th((J>H)4 (a) Titanium Ti, 48 1 HjTiO., (b) ■ (a) Uranium 11,239.6 uos (b) Tantalum Indium Ta, 1 82. 6 In. 113. 7 IIjTaO, InS Niobium Nh,93.7 , H,Nb04 Thallium Th, 204.2 Th,S (d) [Vanadium I V, 51 ! Not prc- linitattd RARE METALS. 177 Uses. — These rare elements do not as yet find much application in the arts. Zirconium is used in the manufacture of the so- called "Welsbach gas mantles," where it assists in the "incandescence." Uranium is used as a chemical reagent. Uranium acetate finds considerable application in the volumetric estimation of phosphates. Cerium is found in many minerals, but especially in cerite — a silicate. Cerium oxalate is its important medicinal salt, 062(0204)3-1-91120. Made by precipi- tating cerous chlorid with ammonium oxalate. The official cerium oxalate is not a pure salt, but is a mix- ture of the oxalates of cerium, didymium, lanthanum and other rare earths. The rare elements of the alkalin group comprise Rubidium, Rb, 85.3, and Cesium, Cs, 132.6. These possess almost identical characteristics with potassium and can be detected only with difficulty. Their sepa- ration is based upon the -comparative solubility of their chloro-platinates. They play no special part in ordinary chemistry or pharmacy. 178 PHARMACKUTIC CHEMISTRY. VALENCES OF THE METALS. Sym- bol Valence n "ous" com- pounds Valence in "ic" com- pounds Atomic weights Ag Pb Hg' As Sb Sn Bi Cu ?r Fe Co Ni Mn Zn Al Cr Ca Sr Ba Mg Li Na K (NHJ Silver Lead Mercury (ous) Arsenic Antimony .... Tin Bismuth Copper Mercury (ic). . Cadmium .... j ron Cobalt Nickel Manganese . . . Zinc A]uminum . . . Chromium . . Calcium Strontium. . . . Barium Magnesium. . . Lithium Sodium Potassium. . . . Ammonium . . 3 3 3 3 2 3 4,6 2 107. 1 205 -3 198.3 74-4 II9-3 118. 1 206. 9 63.1 198.3 III. 6 55-5 58. 5 58.3 54-6 64.9 26.9 51 -7 39-8 86.9 136.4 24. T 6.9 22.8 38.8 THE IONIC THEORY.— When solutions are sub- jected to tlie action of an electric current, a decom- position known as electrolysis takes ])lace, and tlie minute particles separated, called "ions," are at- tracted to the positive pole, called the electric aiiodc, and to the negative pole, called tJie cathode. The ions attracted to the anode, positiw pole, iire eUrIro- VALENCE. 179 positive ( + ), and are called anions. Those col- lecting at the negative pole ( — ), or cathode, are electro- negative, and called cathions. As a general rule, the metallic elements form positive ions and the non- metallic, negative ions. The positive ions attract the negative ions and repell the positive, the inverse being true for the negative ions. . The polarity of an ion may, however, be changed by the inducing action of other ions. Valence. — By analysis of a great number of hydro- gen compounds, it has been determined that dif- ferent elements combine with it in definite propor- tions, but that these proportions vary in different compounds and with different elements. It was found that chlorin unites with hydrogen in propor- tion to its atomic weight. Thus: 35.4 parts by weight of chlorin unite with i part by weight of hydrogen. But oxygen unites in half its atomic weight, or requires two atoms of hydrogen to one atom of oxygen. Nitrogen similarly requires three atoms of hydrogen; carbon, four atoms, etc. This power of combination is known as valence, and the valence of any element depends upon the number of atoms of hydrogen or its equivalent that the element will unite with or replace in a compound. PHYSICAL CHEMISTRY AND ELECTRO- CHEMISTRY. At the present time two distinctive and very im- portant branches of chemistry are receiving much consideration and study; these are physical chemistry l8o IMIAKMACErilC CUEMISTK V. iind eUrtrofliciiiislry. Tliese Ijranchcs make use of the i)hvsical constants to determine the characteristics, properties, etc., of any element or compound. Close study is made of the effects of heat and cold, light, color, pressure, temperature and their changes, polari- metric properties, etc., are all taken into account. In electrochemistry the distinctive properties of the electric current are made use of and api)lied in the arts. Thus, union among the gases may readily l)c l)n)Uglit al)()ut l)y llie action of an induction sj)ark. Bv passing the galvanic current, however, such union of gas may again he resolved into its con- stituents. We can, therefore, employ the electric cur- rent for i)oth synthesis and analysis. Decomposi- tion of compounds by electric current is called electro- Ivtic; the operation, electrolysis. Thus, a sohilion of zinc sulfate may l)e electrolyzed according lo tlie following equation: ZnS()4 + (electric current) = Zn (at cathode) + SO^ (at anode). The ele(troi)osi- live metallic zinc is deposited at the negali\e pok' (cathode) and the electronegative radical (SO,) sepa- rates at the positive pole (anode). The substance to be electrolyzed must be in a gaseous, licjuid.or fused con- dition, and is known as electrolyte. The particles into which a salt will chHiroly/.e are called "io)is'\ thu>, zinc sulfate is lomposed of two ions— Zn and the (SO4) radical. Application 0/ the electric current is made use of in chemical analysis for depositing the metals, which can l)e done quantitatively, and in e!ectrotyi)ing- or (h-- ])ositing of a la\cr of copper over moulds or tyju — I UNIVERSITY J) ^ = = ELECTRICITY. l8l for the purpose of reproducing the same. Electro- types are made use of in the printing of books, maga- zines, maps, etc., and are made from the forms set up by the printer. Such electrotypes can be preserved for subsequent use. Electroplating is the process of depositing electro- lytically one metal upon another — usually a cheaper one. Eleclrxity is also used in the refining oj metals, preparation oi caustic alkalis, chlorates, hypochlorites, white lead, Prussian blue, etc., also many organic compounds. CHAPTER XVIII. CHEMICAL NOMENCLATURE AND CHEMICAL FORMULAS. Berzelius (1815) proposed the short-hand form of chemical language; since that time, we are employing a system of symbols and symbolic formulas for the elements and compounds. In Chapter II simple definitions were given for the acids, salts, etc. It is difficult — almost impossi- ble — to give concise definitions in chemistry. BASE is a term properly appHed to a combination of a basic oxid with water, thus, Na^O + HjO = 2NaOH, called sodium hydroxid, hydrate, or simply soda; CaO + U^O = Ca (OH),, called calcium hydroxid, hydrate, etc., are bases. Sodium oxid, Na,©, calcium oxid, CaO, are incor- rectly termed bases. ACID (1) is a com])()und of an electronegative element or radical with hydrogen, part or all of which can be exchanged for an electropositive clement without forming a base. (2) An acid is a salt of hydrogen. An acid can be produced by combining an anhydrid with water; thus, N2O5 -f HjO = 2HNO3 = nitric acid. Elements like S, CI, Br, 1, etc., combine with hydrogen directly, forming acids; thus, sulfur i)roduces US = hydrosulfuric acid; iodin produces HI = hydriodic acid, etc. 182 NOMENCLATURE. 1 83 SALT is hard to define concisely: (i) Salt is an acid in which the hydrogen has been replaced either in part or entirely by a metal or radical. (2) Salt is a combination of an anhydrid with a basic oxid; thus, Na.O + N2O5 = 2NaN03. Salts may be normal, acid or basic. ANHYDRID is an acid oxid. It is the part of an acid remaining after the removal of the elements of water. Anhydrids combine with water to form acids. 2HNO3 — H2O = N2O5 = nitric (oxid) anhydrid. nitric acid H2SO4 — H2O = SO3 = sulfuric (oxid) anhydrid. sulfuric acid With water these anhydrids re-form the acid: SO3 + H.O = H.,SO, = sulfuric acid. EMPIRIC FORMULA is the expression of the simplest ratio of the elements composing a com- pound. Thus, Fe03H3 is the empiric formula for ferric hydroxid, and CH^O, the empiric formula for acetic acid. MOLECULAR FORMULA is the expression of the actual number of atoms of each element in a molecule. It may be identical with the empiric formula or a multiple of it; thus, CjH^Oj is the molecular formula for acetic acid. TYPE FORMULA is a molecular formula arranged after one of the three common types: /H H— O— H -> H— CI - ^ N— H water type hydrochloric \H acid type r- ammonia type ISOMERISM is a term designating bodies having 184 PHARMACEUTIC CHEMISTRY. the same cnipirit- f(jrmuhis but different proj)erties. Isomerism applies to compounds, while to elements is applied the term — ALLOTROPISM, a term designating those modifiT cations of an element which present different physical properties. Thus, phosphorus exists in two modifications: the yellow, which is inflammable and poisonous, and the red, which is noninflam- mable and nonpoisonous. Carbon exists in three allotropic forms: diamond, graphite and coal. POLYMERISM applies to compounds having the same empiric but different molecular formulas; thus, aldehyd has the formula CjH^O; its polymer paraldehyd has the formula CgHjjO^; it is derived by multiplying the aldehyd formula by 3. HOMOLOGOUS SERIES is a group of substances with similar projierties, whose molecular weights have a common difference; thus, the paraffin series differ by CHj group from one another and l)y 14 in their molecular weights. ISOLOGOUS SERIES in organic chemistr}- ap- plies to substances differing by H^; thus: C2Hg= ethane; CjH^ = ethylene; C^H-, = acety- lene, are isologous compounds. AMORPHOUS is api)licd to ])odics incai^nble of crystallization. MONOMORPHOUS, ca])able of crystallizing in one form. DIMORPHOUS, crxstallizing in two forms, as sulfur. TRIMORPHOUS and POLYMORPHOUS are terms NOMENCLATURE. 1 85 applied to bodies crystallizing in three forms and many forms, respectively. ISOMORPHOUS is u term applied to dit^'ercnt jjodies crystallizing in the same form. ALLOY is a mixture of two or more metals. AMALGAM is a term applied to the union of a metal with mercury. (Hg does not amalgamate Fe or P.) EFFLORESCENT substances are those which lose their water of crystallization at ordinary tempera- tures (Na^COg). DELIQUESCENT substances are those which absorb sufficient water from air to form a solution at ordinary temperatures (KOH). PHARMACEUTIC CHEMISTRY EQUATIONS. 187 EQUATION WRITING. A Sludy oj Chemical Changes. Under certain condiliDns all material bodies may undergo certain changes. When these changes occur within the molecular structure of these bodies, they may be said to be "chemical changes." Thus, when two bodies upon coming in contact exert an action on one another, such action is called a reaction. A body which when added to another body causes such a change is called a reagent; the results oj the reaction are called products, and the reactive bodies are termed factors. Thus, when metalUc zinc is brought in contact with sulfuric acid, zinc sulfate is formed and hydro- gen gas is given off. Thus, zinc is the reactive body, H2SO4 the reagent, zinc sulfate and hydrogen gas are the products, while zinc and the acid have served as the factors in the reaction. Equations are representations of chemical reactions by means of symbols and algebraic signs. In writing equations, the symbolic formulas of the factors, united by the plus sign ( + ) are written to the left of the equality sign ( = ), while the symbolic formulas of the products, also united by the plus ( + ) sign, are written to the right of the equality sign. The reaction between zinc and sulfuric acid is illustrated by the following equation: The factors: The products: Zn + H2SO, = ZnSOJ+H sulfuric zinc jhydrogen acid sulfate | lOS PIIARM ACEITIC CIIKMISTRY. In another chapter it has been slated that syiuhols represent definile weights. Equations can therefore l)e easily reduced to figures. Thus, atomic weights of the elements entering in the above equa tion are zinc = 65; H._,SC)^ e([uals H = 2, S = 32, = 16. We had, therefore, 65 parts of zinc reacting with 98 parts of sulfuric acid, which produced 161 parts of zinc sulfate and 2 parts of hydrogen. If we examine further into this reaction, we will see that the total atomic weight of the factors to the left of the sign of equality is 163, and that those of the product to the right is found to be the same. In a correctly written ecjuation the sum-total of the atomic weights on both sides of the sign of equality must balance and so must the number of atoms on each side. The fol- lowing should be remembered while constructing equations: (i) That positive atoms unite only with negatives, and not with postives. (2) That the valences of the atoms and radicals must in all cases he satisfied (saturated). (3) That the members of an equation must repre- sent whole molecules. (4) That compound radicals usuall)- remain as such in the products. (5) That acids and bases neutralize each other and therefore cannot exist in the same solution. (6) That an equation nmst balance before it can be regarded as completely representing a chemical change. EQUATIONS. 109 A thorough knowledge of the rules of writing chemical equations is of absolute importance, and the student should pay most careful attention to them. By the method of presentation given below the student can quickly grasp the gist of the subject. The simpler equations are discussed first, followed by the more complex and difficult ones. Equations may he divided into jour classes: (0 Analytic Equations.— Under this heading are included those equations which represent the split- ting of more complex compounds into simpler ones. Thus, when potassium chlorate is heated, it splits up into potassium chlorid and oxygen. This can serve as a typical equation representing analysis (from ana, up; lysis, separation): (./) 2KCIO, = 2KCI + 30^ potassium = potassium + oxygen chlorate chlorid Mercuric oxid splits into mercury and oxygen: {b) 2HgO = Hg3 + _^___ mercuric = mercury + oxygen oxid By means of electricity, water can be decomposed into its elements — hydrogen and oxygen: (c) 2H,0 = JH_4 _ , + Q. water = hydrogen -f oxygen (2) Synthetic Equations.— Under this head belong equations representing the union of elements to form compounds, also the union of simpler com- pounds to form more complex ones. A type of synthetic (from syn, together; thesis, bringing) igo PHARMACEUTIC CHEMISTRY. reaction is tiie following, which represents the forma- tion of water from its elements: (a) 2H, 4- O, = 2H,0 The formation of iron sulfid from its elements: (b) 2Fe_ + S. = 2FeS iron -f sulfur = iron sulfid The formation of sulfur dioxid in the process of burning sulfur in the air; the sulfur vapor combining with the oxygen of the air: (c) S, + 20^ = 2SO^ sulfur + oxygen = sulfur dioxid (3) Single Decomposition Equations. — Under this heading are included those reactions in which one of the factors is split, the other remaining intact. The action of hydrochloric acid on zinc, in which the acid splits into its elements (hydrogen and chlorin), serves as a type : (a) Zn + _jHCl = ZnCl, + H, zinc + hydrochloric =zinc chlorid + hydrogen acid When dilute sulfuric acid acts on iron, iron sulfate (ferrous sulfate) is formed and hydrogen is set free. (The iron sulfate may be called a product, while the hydrogen in such operation is usually termed a by-product.) (b) 2Fe + 2H,S04 = 2FeSo 4 + 2H, iron + sulfuric acid = iron sulfate + hydrogen When iron hydroxid is heated in a stream of hydrogen, reduced iron (ferrum reductum U. S. P.) is formed: (f) 2Fe(OH), +_ 3H, = Fe^ -f 6H,0 ferric hydroxid + hydrogen = iron + water EQUATIONS. 191 (4) Double Decomposition Equations. — Under this heading belong those equations in which both the factors suffer decomposition. Thus, in the action of hydrochloric acid on potassium hydroxid, potassium chlorid and water are formed, showing that both the acid and the potash were decomposed. The following may serve as a type for the fourth class. (a) KOH + HCl = KCl + H^O potassium + hydrochloric = potassium + water . hydroxid acid chlorid When hydrochloric acid acts on zinc oxid, zinc chlorid and water are formed: (6) ZnO + 2HC I = ZnCU + H^O zinc oxid + ac. hydrochloric = zinc chlorid + water When hydrochloric acid acts on ferric oxid, ferric chlorid and water are formed: (c) Fe.03 + 6H C1 = 2FeCl3 + 3 H.O ferric oxid + ac. hydrochloric = ferric chlorid + water Rules for writing Equations. — All of the commoner equations belong to one of the four classes just dis- cussed. The seven rules following embrace all of the reactions common to pharmaceutic procedure. It will be observed that most of the reactions belong to the fourth class (double decomposition) . Students will do well to memorize these rules correctly, and frequently practice equation writing. Equation writing is of inestimable value in quickly grasping chemical changes and theories. Rule I. — Whenever a hydroxid of a metal is dis- 192 PHARMACEUTIC CHEMISTRY. solved in an acid, a salt oj the metal and water are produced; thus: (i) KHO + HCl = KCl + H,0 potassium hydrochloric pcjtassium water hydrate acid chlorid (2) 2KHO + H,S04 = K.SO^ + 2H,0 potassium hydrate sulfuric acid potassium sulfate water Ca(HO), + 2 HCl CaCl, + 2H,0 calcium hydrate hydrochloric acid calcium chlorid water 2Fe(HO)3 + 6HC1 = 2FeCl,, + 6H,0 ferric hvdratc hydrochloric acid ferric chlorid water (.s) (4) Zn(HO) , + H,S0 4 = ZnS04 + zH^O zinc sulfuric zinc water hydrate ai id sulfate Rule II. — Whenever an oxid oj a metal is dissolved in an acid, a salt oj the metal and wat^r are produced (the only excei)ti()ns beiiiff the higher oxids of the metals); thus: (i) (2) CaO + 2HCI CaCl. + H,0 calcium oxid •i) 'drochloric acid calcium chlorid water BaO + 2 HCl liaCl, barium chlorid + _ H,() liarium oxid •dnxhloric arid water EQUATIONS. " ^ Fe,0, + 6HC1 ^ 2FeCl3 4- 3H^O ferric hydrochloric ferric water oxid acid chlorid MgO + H,S04 = MgS04 + H,0 magnesium sulfuric magnesium water oxid acid sulfate CuO + 2HNO3 = Cu(NO,0, + H,0 copper nitric copper water oxid acid nitrate PbO + 2HNO3 _ Pb(NO,). + H,0 lead nitric lead water oxid acid nitrate Sb^O,, + 6HC1 = 2SbCl3 + 3H.O antimony h ydrochloric antimony water oxid acid chlorid (3) (4) (5) (6) (7) Rule III. — Whenever a carbonate oj a metal is dissolved in an acid, a salt oj the metal, water and carbon dioxid {carbonic-acid gas) are produced, the latter is given off. In equations the radical of the carbonates (€0^) splits up into CO^ and O, the former escaping, the latter uniting with the H^ to form ivater; thus : (i) (2) CaCO,, + 2HNO3 = Ca(N03). + CO. + H,0 calcium carbonate nitric acid calcium carbon nitrate dioxid water K.COj + 2HCI = 2KCI + CO3 + H.O potassium carbonate hydrothloric acid potassium carbon chlorid dioxid water 194 PHARMACEUTIC CHEMISTRY. Na,C03 + H,S04 = Na.S04 + CO, + H,0 sodium sulfuric sodium carbon water carbonate acid sulfate dioxid Rule IV. — Whenever a metal is dissolird in hydrochloric acid or in aqua regia, a chlorid oj the metal is akcays formed and hydrogen given of]; thus: (0 (2) Rule V. — Whenever a metal is dissolved in dilute sulfuric acid, a siiljate oj the metal is ahvays formed and hydrogen given off ; thus: Zn + H,S04 = ZnS04 + ^H^ (2) Fe, iron + 4HCI = hydrochlor'c acid 2FeCl. ferrous chlorid hydrogen Pb + 2HCI PbCU + H, lead hydrochloric acid lead chlorid hydrogen zinc sulfuric acid zinc sulfate hydrogen 2Fe + 2H,S04 = = 2FeS04 + 2H, iron sulfuric acid ferrous sulfate ■ hydrogen Rule VI. — Whenever a metal is dissolved i)i strong sulfuric acid, a suljate oj the metal and water are formed, gaseous sulfur dioxid {SO^) evolved. The sulfates usually made by the action of strong sulfuric acid on the metals are mercury, copper and silver sulfates ; thus: (0 Hk + 2H,S04 = = HgSOj + ^0, + 2H/:) mercury sulfuric acid nuTcuric sulfur water sulfate dioxid (2) (3) EQUATIONS. 195 __2CU copper + 4H.SO4 = sulfuric acid = 2CUSO4 copper sulfate + 2SO. + 4H.O sulfur water dioxid 2Ag silver + 2H,S04 = sulfuric acid = Ag,S04 silver sulfate + SO- 4- 2H-O sulfur water dioxid It should l)e noticed that twice the required quantity of the acid is taken to furnish VSO4 for the sulfate, the extra SO4 spHtting up into SO2 and O2. The former escapes and the latter unites with the hydrogen to form water. Rule VII. — The ordinary metals {excepting tin, antimony, arsenic and zinc), when acted upon uith slightly diluted nitric acid, form metallic nitrates and evolve nitric oxid (NO); thus: (i) (2) (3) (4) (5) 6Ag + 8HNO, = 6AgN03 + 2NO + 4H.O silver nitric acid silver nitrate nitrogen water oxid 3Pb + 8HNO3 = 3Pb(NO,). + 2NO + 4H2O lead nitric acid lead nitrate nitrogen water oxid 3Hg + 8HNO3 = 3Hg(N03), + 2X0 + 4H20 mercury nitric add mercuric nitrate nitrogen watf-r oxid 3Cu + 8HNO3 nitric acid = 3Cu(N03). copper nitrate + 2NO + 4H,0 copper nitrogen water oxid 2Bi + 8HNO3 = 2Bi(N03)3 + 2NO + 4H20 bismuth nitric acid bismuth nitrate nitrogen water o.xid 196 PHARMACEUTIC CHEMISTRY. It should he noticed that eight equivalents of nitric acid arc employed for every six eqtiivalents oj the metal. This is true of all the reactions of HNO., upon the metals; the by-products always being 2 molecules of nitric oxid and 4 of water. STOICHIOMETRY.— It is often necessary to con- sider, by means of figures, the relation of the atoms in a molecule, or of molecules in a compound; a'so to determine percentage composition, the weight of certain volumes, etc. For this purpose stoichiometry, or "chemical arithmetic," is made use of. All cal- culations in which use can be made of atomic weights and vo'umes are included in this class. As stated, every element has its atomic weight, and every molecule and compound, therefore, has its value expressible in figures. As already shown, all chemical changes take p'are between definite amounts of substance, and a chemical equation expresses the amount of matter taking ])art in it; thus, a reaction may be written: H,S04 + 2NaOH = 2H2O -f Na^SO,. 98 + 2(40) = 2(18) +142. The lower figures of the equation represent the quantities that take part in the reaction and express molecular weights. ' The percentage of any molecule or atoms may be easily determined by comparing the quantitx of the on(> desired with the total, on fhel)asisof 100. 'I'lui^, in our reaction just stated, if the amount of sodium sulfate produced is desired in i)ercentage, the pro- portion would be 142 : 178 : : x : 100. STOICHIOMETRY. 197 The same process of calculation would give us any factor ; thus, if the percentage of sodium as an element were desired, the proportion becomes 2(23) : 178 : : X : loo. Any ofher modification may be readily deduced. Care must be taken that the proper atomic weight, or multiple of it, be used in both reagent and product. In the example given, two molecules of sodium hydrate were required to form one molecule of sodium sulfate, and twice the atomic weight of sodium entered into both factors. If the problem had been, how much sodium sulfate would be obtained from lo grams of sodium hydrate, the proportion would remain the same, substituting 10 for 100. The answer would then be in grams instead of in per cent. Exactly the same calculation is employed with a single molecule as in equations; thus, if the amount of sodium present in lo grams of sodium sulfate were desired, the proportion would be Na2S04 = Na, + S + 0„ or (46 + 32 + 64) 46 : 142 : : X : 10, etc. Modifications of this may be readily deduced. If volumes instead of weights came into the problem, the proportion is still the same, but each molecular formula represents two volumes, since, as previously stated, molecular weight is twice that of density, which, in turn, represents but one, and by considering each molecule as twice that stated, direct calculation may be made. Example: How much carbon dioxid can be made by burning one 198 PIIARMACKUTIC CHEMISTRY. ' liter of carhon monoxid? The reaction (CO)2 + O, = (CO,), read 4 vol. (CO) + 2 vol. (O,) = 4 vol. (CO,) and 4: 4 : : i : .x. .x = i. i liter of CO, produced. If the relation of weight to volume or I'ire versa is desired, divide the weight of the gas by its weight per liter, the quotient will be the numberof liters; or multi- plying the number of liters by the weight per liter gives the weight of the given volume. The original weight or volume is determined as stated in the last two proportions respectively. Influence of temperature and pre isure on gas volumes enter the calculations: According to Boyle's law, the volume of any gas var'es inversely as the pressure, and its density directly as the pressure; hence, gas volume changes with the baometric pressure. Normal barometric pressure is 760 mm. of mercury, the factor being, therefore, 760. Similarly, all gases vary directly as the tempera- ture. Absolute zero is taken as — 273° C, and it is claimed, therefore, that a gas volume increases ^i^ of its volume for each degree increase in temperature above 0° C. In order to correct a gas volume, there- fore, to standard conditions, the following procedure may be followed: The formula y VP 760 X I -I- (.003661), in which \'' = desired volume; V = stated volume; p= barometric reading; 760 = normal barometric reading; i = normal temjjerature, and .oo366 = faclor ^i-^; t = stated temperature, is used: STOICHIOMETRY. igg Example: What would be the normal volume of a gas whose volume, at 42° C. and with barometric read- ing 732, was 976 cubic centimeters? Substituting in the formula we have: V = 976 X7H2 ^ 7 I44.S2 760X I + (.00366 X42)., 876.827. Ans. =814.7 c.c. at 0° C. Modifications of this may be easily deduced bv transposition of factors. Very many other uses may be made of stoichiometryand mathematics in chemis- try, but a full disscusion would require a volume in itself, and those given are but the foundation for manv others. PHARMACEUTIC CHEMISTRY. PART II. ORGANIC CHEMISTRY. CHAPTER XIX. INTRODUCTION. The compounds of carljon with other elements, such as hydrogen and oxygen, are so numerous that it is necessary to devote to them a special part of the study of chemistry, namely, "organic chemistry." Berzelius (1818) defined organic chemistry as the chemistry of bodies formed under the influence of life. When, however, Woehler, in 1828, in an en- deavor to evaporate an aqueous solution of ammo- nium cyanate, found the residue composed of a sub- stance different from ammonium cyanate, namely urea, the theory that "vital force " was necessary to |)roduce these compounds became untenable. It was found that they could be produced synthetically in the laboratory of the chemist, and the original belief that organic substances could only be produced by animal or vegetable organism was found to be wrong, and a new definition for organic chemistry had to be sought. Liebig (1832) defined the science as the "chemistry of compound radicals." But, whereas 201 202 I'HARMACEUTIC CHEMISTRY. almost any molecule with more than two atoms may be supi)osed to contain a compound radical, that definition, it will be seen, is inaccurate; and, besides, there are many inorganic compounds which also con- tain compound radicals, thus, NH^, NO3, SO4, etc. Since carbonic oxid, carbonic sulfid, carbonic acid and their salts are usually excluded from works on organic chemistry and studied in conjunction with the inorganic compounds, as containing incom- bustible carbon, it will be seen that the present defini- tion is most probably correct, although by some it is claimed to be too broad. Organic chemistry is now defined as the study of the carbon compounds. Thus, we have seen that the discovery of urea in 1828 marked the rise of true organic chemistry, and since then over one hundred thousand organic com- pounds have been prepared synthetically from carbon and the inorganic elements in the chemist's labora- tory, duplicating many of nature's own products. It is safe to assume that every natural product will be duplicated in the laboratory, and, indeed, many which have never been detected in nature have been created there. It may be stated that urea was not really a synthe- tic product, because it was only converted ammonium cyanate which, in turn was not obtained synthetically, but it has since been demonstrated over and over that this compound can be built up atom l)y atom from its elements. 'IMuis, if nitrogen gas is passed over charcoal and potassium carbonate, mixed and ORGANIC CHEMISTRY. 203 heated to redness, potassium cyanid is formed; and if the cyanid, in turn, is fused with lead oxid, it takes up the oxygen, becoming converted into potassium cyanate. Ammonia, on the other hand, can be formed by the direct union of nitrogen and hydrogen and absorbed by water; and if sulfuric acid be added to it, it is neutralized and converted into ammonium sulfate. If, now, the potassium cyanate and the ammonium sulfate be dissolved in water, the solution evaporated to dryness and the residue exhausted with alcohol, upon evaporation the alcohol deposits urea, the following decomposition having taken place: 2KCNO + (NH 4),S04 = K,S04 + 2Cq(NH,)3 potassium + ammonium = potassium + carbamid cyanate sulfate sulfate (urea) Thus, we have seen urea built up atom by atom from the elements; whereas, in the discovery of Woehler, it was a simple rearrangement of the atoms in the molecule, thus: NH.CNO = Cq(NH,), ammonium = urea cyanate THE SCOPE OF ORGANIC CHEMISTRY.— Until the beginning of the nineteenth century, chemistry was concerned mostly with the products of the mineral kindgom or with those of the animal and vegetable kingdoms. Those from the latter two kingdoms, which Lavoisier (1794) showed to contain carbon, hydrogen and oxygen, were called " organic " and those which were obtained from the mineral kingdom, like common salt, gyj^sum or water, were 204 PHARMAC'Eimc CHEMISTRY. tailed the "inorganic." Hut among those of the organic compounds which contained like substances, many possessed different, varying properties. Thus, sugar, vinegar and alcohol contain the same elements — carbon, hydrogen ando.xygen — but their properties are very different because the elements exist there in very variable proportions. Berzelius (1814) so im- proved the methods of organic analysis that it was possible to make determinations of the exact composi- tion of the organic acids and to establish the atomic ratio of the constituent elements one to another; and, although the discovery of Woehler was well known, as was the discovery of acetic acid by Melsens (1842) and Kolbe (1844), it was a long time before the be- lief that vital activity was necessary for the produc- tion of organic compounds, disappeared. There is a difference between an organic compound and an organism. Compounds can be created artificially, organisms cannot. For this reason it is safe to believe that the solution of the problems of life's creation is as yet afar off and the breech between the laboratory creation and that of the organism may never be mended. At least, it is far distant at the present time. At the time of Woehler's discovery, organic chemistry embraced but a few hundred substances derived from the animal and vegetable sources. Now it contains, as has previously been stated, over one hundred thousand artificial products. This most extraordinarv development can be traced directly to two ])rincipal causes: the first one was ORGANIC CHEMISTRV. 205 the formulation of the laws underlying the struc- ture of organic compounds by Kekule, and the second, the industrial application of the organic discoveries. At the present time the contributions of organic chemistry to mankind are many and varied. Thus, foods, medicines, dyes, soaps, nitrogly- cerin and dynamite, paper and celluloid, perfumes, ink, artificial silk, are all organic compounds, and at the present time there seems no apparent limit to the development of the industries in which organic chemistry plays an important part. DISTINCTION BETWEEN ORGANIC AND INOR- GANIC CHEMISTRY.— The necessities for this division are, primarily, the large variety and com- plexity of organic compounds, as will be seen by the following examples: Methane, CH, Turpentine, CjoH^g Cane-sugar Cj.^H220n Morphin, Q7H19NO3 Hematin, C32H32FeNjOg Starch (soluble), C1200H2000O1000 Secondarily, owing to the different reagents and proc- esses necessary for the production of the variety of compounds, each one requires a treatment of its own. Thus, we can oxidize iron with either nitric acid, chlorin or potassium permanganate, tlie result in each case being the same; not so with the organic sub- stances where, by the employment of these different oxidizing agents, a different product would be ob- 2o6 I'HARMACKUTIC CHKMISTRV. taincd in each case. Lastly, because the study of organic compounds cannot be limited to the knowl- edge of their components. They are very com])lcx in structure. One who has studied inorganic chemistry wilf recognize at sight HNOg to be nitric acid and HjSO^ to be sulfuric acid; but to see a formula like CijHjoOu, it is entirely different. Many organic substances have the same composition and molecular formula, but ditYer in their ])roperties. Such substances are called isomeric {isos, equal; meros, part). Isomerism is a striking characteristic of many organic compounds; thus, the formula CgHjjO^ represents 66 different compounds. To illustrate, a familiar example is taken: Alcohol, CjHgO, is a liquid having a boiling-point of 78°, whereas C2HgO is also the formula of methyl ether, also called- dimethyl ether, a liquid having a boiling-point of — 23.6° C. This difference in the two compounds, having the same composition and molecular formula but different properties, is due to the arrangement of the atoms in the molecule. Thus, the carbon, hydrogen and oxygen are ar-ranged in the alcohol and the methyl ether as follows: CH, C H, I I CH2 O I I OH CH3 alcohol methyl t thcr Tlie above substamcs, tlierofore, are isomeric, or one. is an isonier of tin- olher. CHAPTER XX. CARBON. The principal forms of carbon are : (lo\e, or it can be made artiticially by heating oxalic acid, in \vhi(_h case CO is given off during the decom- position, or, still, by the interaction of sulfuric acid and oxalic acid. Reaction: QH^O, + H2SO, = CO + CO2 + H,0. It is also produced in the manufacture of water-gas at high temperatures; thus, C + H.O = CO 4- H,; whereas, at lower temperatures CO, forms. Reac- tion: C + 2H.,0 = COo -I- 2H.,. With nickel, CO (carbonyl) forms a compound known as nickel tetracarbonyl, Ni(CO)4. Nickel tetracarbonyl is a liquid employed in dissolving nickel out of low-yield ores, thus: Ni -f 4 CO = Ni (CO),, and on heating, the compound is resolved as follows Ni(CO), = Ni + 4CO. Carbon disnlfid, thiocarbonic anhydrid, C/ , is a clear, colorless liquid, with disagreeable odor, boil- ing at 47° C, sp. gr., 1.51 ; it forms an explosive mix- ture with air. Gciod solvent for sulfur, iodin. fats, resins and rubber. THE NATURAL SOURCE OF CARBON.— T he source c)f carl)on com])ounds in nature is the carbon dioxid (CO..) exhaled by animals into the air. it is absorbed by the leaves of plants and there, in the presence of moisture and by the agency of the sun's rays is converted by the chlorophyl (leaf-green) into ORGANIC ELEMENTS. 209 Starch or similar substance. Thus, xCOj molecules + vH.^O molecules = z molecules of CgHioOs, or starch. With the nitrogen of the air it forms in the plant bodies substances like the proteins, of which albumin is an example. These substances when ingested into the human body are decomposed into water (HjO), carbon dioxid (COj), and urea (CO(NH,),). From the above it will be seen that the changes in the plant bodies are synthetic, while the changes in the human body are analytic. In the plants, energy s formed and stored; in the human body, it is evolved or expended. Elements Entering Organic Compounds. — Carbon compounds contain few elements, but many atoms. They always contain carbon, usually hydrogen, often oxygen and nitrogen, and sometimes sulfur and phosphorus. They are very complex in struc- ture. Thus, hemoglobin, the red coloring matter of the blood, contains in its molecule 600 atoms of car- bon, 960 atoms of hydrogen, 154 of nitrogen, 179 oxygen and, in addition, 3 atoms of sulfur and i of iron. Whereas, in inorganic chemistry, we deal with about 85 elements, each capable of forming but a few compounds, carbon, on the other hand, is capable of forming such great multitude of. com- pounds with so few elements, it becomes a matter of great curiosity how this can occur. The reason for it is, besides the already-mentioned isomerism, a very interesting fact, namely, that carbon can unite with itself into chains or rings to a very remarkable 14 2IO I'llARMACEUTlC CHEMISTRY. degree, and around these chains or rings other atoms are attached. A chain is a series of multivalent atoms so combined that free bonds are left unsaturated. Thus, carbon can unite in three ways: linked by one bond and leaving six unsaturated bonds, in which case the linking is known as paraflBnic; linked by two bonds, leaving four unsaturated bonds, in this case the linking being known as olefinic; and, lastly, linked by three bonds, leaving two unsaturated bonds, in which case the linking is known as acetylenic. c= c= c— I II III c= c= c— paraffinic bond olefinic bond acetylenic bond. All the above Unkings are called open chains. Besides these, the carbon links its atoms by alternate double and single bonds, in which case it is km-wn as closed chain or ring linkage, as in the case of ben- zene, in which closed chain of C\ forms a hydrocarbon having the formula C|;H„. H I C /\ H— C C— H - • II I H— C C— H C H ORGANIC COMl'OUNDS. 2 I 1 We have seen similar linkings in inorganic chemis- try, as in the case of oxygen (O = O), and in the O case of ozone X\. The quantivalence oj carbon is always 4. O — O THE CLASSIFICATION OF ORGANIC COMPOUNDS. The immense number of substances comprising the study of organic chemistry renders classification difficult. It is primarily divided into two grand classes or divisions: (i) the methane, paraffin, fatty or marsh-gas series; (2) the benzene, ring or aromatic series. In the first class all the organic substances are considered as derivatives of methane (CH^), and in the second class they are con- sidered as derivatives of benzene (CeH^). Each of these two hydrocarbons forms a variety of deriva- tives which may, for convenience, be divided into classes : (i) Hydrocarbons — compounds containing carbon and hydrogen only, as methane (CH^), benzene (CgHg), naphthalene (CjoHg). (2) Alcohols — hydrocarbon radicals combined with a hydroxyl group, as ethyl alcohol (CjH^OH). (3) Aldehyds — compounds of hydrocarbon radi cals with — CHO group, as acetaldehyd (CH3CHO). They are also defined as the oxidation products of primary alcohols. . (Alcohols less 2H. atoms.) (4) Ketones — compounds of the divalent radical, carbonyl, = CO, united with two monovalent alkvl 212 PHARMACEUTIC CHEMISTRY. radicals, as CH3 — CO — CH3, dimethyl ketone, or acetone. (Also defined as oxidation products of secondary alcohols.) (5) Acids — compounds of hydrocarbon radicals united to a carboxyl group ( — COOH), as acetic acid, CH3COOH. (6) Ethers — compounds of hydrocarbon radicals with oxygen; also defined as alkyl oxids. Example, common ether, also called diethyl ether, CgH^ — O — C2H5. (7) Esters — alkyl salts. They are also defined as acids in which the hydrogen of the carboxyl is replaced by an alkyl. Example, acetic ether, CH3COOC2H5. (8) Carbohydrates — compounds of carbon, with hydrogen and oxygen in the proportion to form water, as glucose, CgHjjOg. (9) Amins and Anids: Amins are ammonias in which one, two or all three hydrogens have been replaced by alkyl groups, as methylamin, NH2CH3, dimethylamin, NH (0113)2, or trimethylamin, N(CH3)3. Amids are acids in which the OH group of the carboxyl has been replaced by the amido (NH,) group, as acetamid, CH3CONH2. (10) Cyinids — compounds and derivatives of cyanogen, C2N2. (11) Proteins — compounds of complex structure, containing carbon, oxygen, hydrogen, nitrogen and sulfur and often ])hosphorus and .iron, as albumin, C72HU2N18SO22, or hemoglobin, C6ooH98oN,54079S3Fc. (12) Acid halids are organic acids in which the ORGANIC COMPOUNDS. 213 hydroxyl has been replaced by a halogen, as acetyl chlorid^ CH3CO.CI. (13) Anhydrids — acids deprived of water, as acetic anhydrid, (CH3CO)20. (14) Or gano-metaUk compounds — alkyl compounds of the metals, as zinc ethyl, Zn(C2H5)2. (15) Alkyl halids — compounds of alkyl with halogens, as methyliodid, CH3I; ethyl bromid, CjHgBr; propylchlorid, C3H7CI. Another method of classification is that based on the composition and properties of many of the members of the different families of organic com- pounds. For instance, in the class of hydrocarbons, each member behaves toward reagents in a manner much like every other member of the same class, and the same may be said of the class of alcohols, alde- hyds and ethers; but although the chemical behavior of each family is the same, the physical properties, such as specific weight, melting-points and boiling- points of the individual members, vary with each member. Thus, increased molecular weight usually shows a higher boiling-point; the first jour members of the paraffin series are gases, the next eight are liquids, while those having the largest carbon molecule are solids. CHAPTER XXI. HOMOLOGY. Upon examination of the first tive members of the methane series, we find that there is a simple ratio of difference between each of the individual mem- bers. It will be observed that the ratio of differ- ence between the members is CHj. It is apparent that the successive members can differ only by the same group, inasmuch as the carbon has but four valences, of which two have been satisfied Ijy the hydrogen and two remain unsaturated. This rela- tion is characteristic not only of the paraffin series, but also of the other hydrocarbon families. This relationship is termed homology, and the individual members arc called homologous. ALIPHATIC SERIES. The Hydrocarbons. The hydrocarbons have been defined as com- pounds of carljon and hydrogen only, and hence their name. They occur in nature in very large quantities and are the starting-point of a whole series of aliphatic or open-chain compounds. Occurrence. — The hydrocarbons found in nature arc almost c.xchisivcly vcgijtablc, very few being animal jji-oducls, nnd they are generally sui)i)osed 2V..\ HYDROCARBONS. 215 to be products of decc^mposition. Several theories have been advanced to explain their formation in nature: First, the chemical theory. Based on the fact that when carbids are treated with water, hydrocar- bons form; thus: AI4C,, + i2H,0 = 3CH4 + 4Al(OH)3 ^ aluminum + water = methane + aluminum carbid hydroxid. Second, the vegetable theory, also called the theory oj petroleum formation. This depends upon the fact that when organisms act upon woody fiber (cellulose), in presence of moisture, as in the case of the decay in the stagnant pools of marshes, hydro- carbons are formed. Thus: (C6HioO,)n + (H^)n = (3CQ.)n -f (3CH.)n cellulose -|- water = carbon dioxid -\- methane Third, the biologic theory. This theory purports that animal remains, under pressure and with suf- ficient water, bring about a reaction resulting in the formation of hydrocarbons. It is difficult at this stage and time to say definitely which of these three theories is the most probable. All three may be correct: paraffins may originate from either animal, vegetable or chemic matter, or all three combined. The hydrocarbons are very important in the sense that they are looked upon as the fundamental 2l6 PHAKMACEirXIC CHEMISTRY. compounds of organic chemistry from which, directly or indirectly, all the other organic com- pounds are derived. They are also important, per- haps, for the reason that comparatively few of the carbon compounds do not contain hydrogen and it is, therefore, practical to consider all organic compounds as either substitution or addition products of the hydrocarbons. All the hydrocarbons, as has been stated before, are divided into series, each having a definite general formula which applies to any indi- vidual member of the entire series. Thus, the most usual classification of hydrocarbons is into the four general classes or series: (i) The methane, paraffin or chain series; (2) the ethylene or olefin series; (3) acetylene series; (4) the benzene, aromatic or ring series. The general formula of the first, or methane series, is CnHjn+a- The general formula of the olefine series is CnHj^. The general formula of the third, or acetylene series, is Cj,H2n_2- The fourth, or ben- zene series, has the general formula of CnH2n_,;- FAMILIAR EXAMPLES OF THE HYDROCARBONS AND THEIR GENERAL PROPERTIES. All students are acquainted with ordinary turpen- tine, also most of you have seen the oils of lemon peel or orange peel. Now you will recall that while the turpentine oil is a colorless, water-white liquid, the lemon oil is a straw-colored liquid, and the oil of orange peel, a still darker ycUow-colorcd liquid. PARAFFINS. 217 One will also recall that the odor of turpentine is very unlike that of lemon and less like that of the orange-peel oil; and ycl, 4% bv vo umc ■„ ■ , °. , „ •' t/ti . lUiimiuants in coal k^s. Benzene J "^ Ammonia gas \ Nitrogen [ <>, ,1 ^ These four gases are the Carbon disuilid { usual impurities of gas. Carbon dioxid J It will be seen from the above analysis that the "diluents" constitute about 90% of coal gas, while the "luminants," rich in carbon and to which the luminosity of the flame is due, constitute but 4% by volume of the gas. The impurities are due to nitrogen (a product of decomposed air which en- ters the retorts in the process of charging them), ammonia, carbon dioxid and the sulfids which es- cape the purifiers. STRUCTURE OF GAS FLAME. A gas flame may be said to consist of three layers: the innermost layer consisting of unburnt gases; the middle layer or luminous layer, consisting of partially burnt gases and minute particles of carbon, which latter impart to the flame its reducing proper- ties and the name "reducing flame" (R. F.); the outermost layer which is colorless, consisting of completely burnt gases. This layer in which the carbon and hydrogen are completely oxidized is the hottest of the three and is called the "oxidizing flame" (O. F.). The innermost flame, therefore, is a mixture of gas and air, the middle layer to which the oxygen of the air, owing to the great heat of the oxidizing GAS FLAME. 247 flame, has no access, consists of partly l)urnt hydro- carbons with particles of carbon rendered incandes- cent so as to emit white light. Free carbon can be detected in this layer by introducing a piece of white porcelain into the flame when the carbon will de- posit on it as soot. In the outermost layer the hydrocarbons are "oxidized" or "burnt " to carbon dioxid and water. This, therefore, is the "hottest" flame. If air is mixed with gas before its ignition, as in the case of the "Bunsen burner," both the carbon and hydrogen become completely "burnt up," furnishing a colorless or " Bunsen flame." A Bunsen burner consists of a gas-jet, the base of which is provided with a perforated collar which admits the air into the jet. The temperature of gas flame is very high, that of a flat burner about 1300° C, and that of a Bunsen burner about 1500° C. The "Welsbach incandescent burner" has ef- fected an enormous economy in gas consumption. Thus, the 86% of hydrogen and methane present in gas, and Vv^hich in the ordinary burner produce barely any light, is utilized in rendering the infusible mantle of the incandescent burner hot, and thus produce a strong white light. CHAPTER XXIII. DERIVATIVES OF METHANE. The structural formula of methane, CH^, is the following: H I I — C— — H~C— H I I carbon skeleton H If one of the hydrogen atoms is substituted by an atom of any other univalent element or a univalent group of elements, a "mono-substitution" derivative is produced. Thus, by substituting the hydrogen atoms of methane with the halogens the following derivatives are obtained: H H H I I I H— C— CI H— C— Br H— C— I I 1 I H H H methyl chlorid methyl bromid methyl iodid If two hydrogens of methane are replaced by two univalent or one divalent atom or group, a "disubsti- tution" product is obtained; thus: H H H I 1 I H— C— CI H— C— Br H— C— I 1 1 I CI Hr 1 methylene chlorid methylene bromid methylene iodid (dichlormethane) (dibrommethane) (diiodomethane) 248 MKTHANE DKEIVATIVES. 24Q If three hydrogen atoms in methane are substituted by three monads, or one dyad and one monad, or by a triad atom or group, a "trisubstitution" product is obtained : H I CI— C— CI CI methenyl chlorid (or chloroform) If all of the hydrogen of methane is substituted by other atoms or groups of atoms, "tetfa-substitution " products are obtained: CI Br I CI— C— CI Br— C— Br I— C— I 1 CI Br I carbon tetrachlorid. carbon tetrabromid. carbon tetraiodid. tetra-chlor-methane) (tetra-brom-methane) (tetra-iodo-methane) Of the above halogen derivatives only the tri- and tetrasubstitution products are of practical importance to pharmacy and the arts. CHLOROFORM.— Trichlormethane(chloroformum U. S. P.)— CHCI3 (Souberain and Liebig, 183 1) is prepared by heating a mixture of chlorinated lime (calx chlorinata), alcohol and water. The mixture when distilled yields chloroform which passes over with the water-vapor and is condensed together with the water, from which it separates owing to its higher specific gravity. It is then redistilled from calcium 250 PHARMACEUTIC CHEMISTRY. chlorid which absorbs the water. Tlie reaction is very complex, and it is su[j|>osed that three changes occur in its formation. The hrst change depends upon the oxygen in the bleaching powder which con- verts the alcohol into aldehyd; the second change depends upon the action of chlorin on the alcohol and the formation of chloral; the third, upon the decomposition of the chloral by the alkalin lime (of the bleaching powder) into chloroform and calcium formate. To illustrate: (0 (2) CH, 1 CH3 + 0= 1 + H^O CH3OH CHO alcoho 1 aldehyd CH3 CCI3 + 3C1,= 1 + 3HCI CHO CHO chloral (trichloraldehyd) f CCI3 i 1 + Ca(OH)2 = 2CHCl3 + CaCCHO^)^ CHO slaked lime chloroform calcium formate (3) Lately the production of chloroform from acetone has almost entirely superseded the process just given. This latter process depends upon the formation of trichloracetone which, u])on being heated with lime, is converted into chloroform and calcium acetate; thus: C=H3 C=Cl3 C=0 + 3Cb = C = + ^HCland I I C=H3 C=H3 acetone trichloracetone METHANE DERIVATIVES. 25: H C=C1, Ca— O + C=0 = Ca— O— C = + CH Cl., lime I I chloroform [{h molecule)] CH3 CH, calcium acetate Description, Uses and Tests. — Chloroform is a color- less, heavy-thin (limpid) liquid, having a sweetish taste and a characteristic (chloroformic) odor. The specific gravity of pure chloroform is 1.525. The official variety, containing a little alcohol for the pur- pose of preservation, has a specific gravity of 1.497 and a boiling-point of 61° C. It is readily soluble in alcohol (constituting the official spirit), ether, etc., and to the extent of 0.5% in water (1:200), forming the official chloroform water (aqua chloroformi U. S. P.). It ignites with difficulty and Ijurns with a greenish, smoky flame. Chloroform is used as a solvent for fats, resins, caoutchouc, phosphorus, sulfur and iodin. The commercial variety contains aldehyd, alcohol, etc., from which it can be purified by mi.xing it with sulfuric acid, separating from this acid, neutralizing with a solution of sodium carbonate, separating from this solution, adding lime to dehydrate it and finally distilling it on a water-bath, adding to the distillate from one-half to one per cent, of alcohol to prevent the formation of its impurity, carbonyl chlorid (COClj), so-called phosgene gas. /CI CHCI3 -1- O = CO + HCl. \C1 252 IMIAKMACKl'TIC CHEMISTRY. Tests jor Purity. — Pure chlorofonii should not color solution of sulfuric acid and chromic oxid green, nor should it discolor solutions of KOH, KI or H2SO4. It should not precipitate silver nitrate. In medicine chloroform is extensively used as an anesthetic (Simpson, 1848). For this purpose it should never be administered in a room illuminated with gas, because the traces of CO which escape combustion, at once combine with the chloroform forming the strongly irritating and irrespirable phosgene gas. As an anesthetic it is safer for chil- dren and women in parturition than for other adults. Externally it is an irritant or vesicant. Tests. — -(i) Chloroform in solutions may be detected by warming together some of it with alcohol, solution of sodium hydroxid and a few drops of anilin, when a strong, irritating and poisonous vapor of phenyl-isocyanid is produced: CHCI3 + C,H,.NH3 + 3NaOH = (C.HQ NC + """" anilin phenyl-isocyanid 3KCI + 3H3O. (2) Heated with an alcoholic solutionx)f potassium hydroxid (saponified), it gives potassium formate and chlorid: CHCl, + 4K()H = HCOOK + 3KCI + 2H,0. (3) Chloroform reduces "Fehling's solution" readily, precipitating red cuprous oxid: CHCI3 + 2Cu() + 5KOH = Cu.O + K,C03 + 3KCI + 3H,(). METHANE DERIVATIVES. 253 (4) When chloroform is mixed with a solution uf betanaphthol in strong potassium hydroxid and the liquid heated to about 50° C, a dark blue color is produced, which gradually changes to green and fmally to brown. CARBON TETRACHLORID.—Tetrachlormethanc, CCI4, is produced by the action of chlorin on carbon disulfid or on chloroform (Regnault, 1840). (i) CS2 + 3a = „<^cii_ + s,cu. carbon carbon disulfid tetrachlorid The two products of the reaction are separated by distillation. (2) CHCI3 + CU_ = CCl, + HCl. Properties, Uses and Tests.— Ca.rhon tetrachlorid is a heavy, colorless liquid which boils at 77° C. Heated with water to 250° C, it decomposes into carbon monoxid and hydrochloric acid. Its specific gravity is 1.593 (20°), and it should be noted that the polychlor derivatives have a high specific gravity, and that the corresponding brom- and iodo-deriva- tives are even heavier than the chlor-products. Carbon tetrachlorid (carbona) is non inflammable and can be used as a fire extinguisher. Like petro- Icum-benzin, the odor of which it similates, it is used in extracting fats from refuse materials, in cleansing stained or soiled fabrics and as a solvent in organic chlorinations, it being unaffected by chlorin. BROMOFORM. — Tribrommethane (bromoformum U. S. P.), CHBrg (Lowig, 1832). The commercial bromoform consists of g(f:'^: of tribrommethane and 254 PHARMACEUTIC CHEMISTRY. 1% of alcohol. It is prepared by methods analogous to the production of chloroform, or by direct bromi- nation of ethyl alcohol dissolved in an aqueous .solu- tion of potassium hydro.xid, until the latter begins to acquire the color of bromin. It is purified in a similar manner to chloroform, which it resembles in odor and appearance. Properties and Uses. — Bromoform is a colorless liquid, having a specific gravity of 2.9 (17°) and boil- ing at 151° C. It is freely soluble in alcohol and ether, but sparingly so in water. It is used in medicine as an anesthetic, antispasmodic and seda- tive; exhibited in a hydroalcoholic solution or emul- sion. IODOFORM. — Triiodomethane (iodoformum U. S. P.), CHI3 (Serullas, 1822). It is prepared by precipitating a solution of iodin in potassium iodid with alcohol or acetone in the presence of an alkali carbonate or. hydroxid. The yellow powder thus produced can be purified by crystallization from alcohol (he.xagonal crystals), or by sublimation (golden yellow leaflets). Reaction: QH^OH + 4I, + 3KXO3 = CHI3 + 5KI -K ethyl alcohol 3CO2 + 2H2O + KCHO2. Properties, Uses and Tests. — Iodoform melts at 119° C, is slightly soluble in water, readily in alcohol, ether, chloroform, benzin, carbon di.sulfid, fixed and volatile oils. It has a strong antiseptic and anes- thetic action (depending on the 96.6% of iodin it contains), and is used as a dressing in surgery. It ETHANE DERIVATIVES. 255 possesses a strong, aromatic, saffron-like odor, which can be masked by traces of cumarin, vanillin, naph- thalin or oil of bergamot. Its chief adulterant is picric acid which may be detected by agitating the sample with a solution of KOH, carefully neutralizing with acetic acid; upon adding KNO3, a yellow pre- cipitate of potassium picrate is deposited. A water solution of iodoform should not yield a precipitate with BaClj (sulfates) or with AgNOj (chlorids). Iodoform is hydrolyzed by alcoholic potash in a similar manner to chloroform. When heated with zinc dust and water, iodin is evolved and methane formed; thus: 2CHI3 + 3Zn. + 3H2O =3Znl2+ sZnO + 2 CH,. CARBON TETRAIODID.— CI,, was at one time introduced as "odorless iodoform." It is prepared in a manner similar to carbon tetrachlorid. • DERIVATIVES OF ETHANE. Under Methane we have seen that by a process of gradual substitution of chlorin for the hydrogen of marsh gas, we have changed it into carbon tetra- chlorid: H H H I 1 I H— C— H — H— C— CI -^ H— C— CI -> I I I H H CI H CI I I CI— C— CI — CI— C— CI I I CI CI 256 PHARMACEUTIC CHEMISTRY. In a like manner, bromin, iodin and other mono-, di-, tri-, and tetra-substitution products may be formed from methane as well as other hydrocarbons. Thus, from ethane we may get the following: H H H I I I H— C— H H— C— H H— C— H I -. I - I -^ etc. H— C— H H— C— CI H— C— CI I I I H H Cl^ ethyl chlorid "ethylidene chlorid" (dichlorethane) The halogen derivatives of ethane are less important and interesting than those of methane. CH, ETHYL CHLORID, | , is a limpid, colorless CH2CI liquid, boiling at 12.5° C. It burns with a greenish, smoky flame, is jjut sparingly soluble in water, but freely in alcohol (this solution is called "chloric ether") and ether, etc. When heated with potas- sium hydro.xid, it forms alcohol: C2H5CI + KOH = KCl + C2H5OH. When it is treated with chlorin in direct sunlight, it yields the di-, tri-, tetra-, etc., substitution products of ethane. Used as local anesthetic. ETHYL lODID, iodoethane, C2H5I, is formed when a mixture of strong hydriodic acid and alcohol is heated; or 1)\- adding to a mixture of red phosphorus and alcohol, iodin, little by little, and then distilling on a water -bath. I""th\l iodid is a highl\- refractive. KTHAXE I)KRI\"ATIVKS. 257 very heavy liquid, having an ethereal odor, boiling at 72°, with a specific gravity of 1.94 (14°), and similar in its properties to ethvl chlorid and iodid. ' CH ETHYL BROMID, | , or bromethane, is CH.,Br formed when ethane is heated with strong h\ dro- bromic acid, or it can be produced by distilling a mixture of sulfuric acid, alcohol and potassium hromid. The distillate is washed with alkalin car- bonate and redistilled from calcium chlorid. It is a colorless, limpid liquid, with a chloroformic odor and a burning taste, boiling at 38°, and re- sembles chlorethane in its behavior with alcoholic jjotash. Other Mouolhilogen Derivatives. — The more im- portant are propyl bromid, C3H-Br; but}l iodid, C^Hgl; propyl iodid has two isomers — nornuil ])ro])yl iodid, CH3 — CHI — CH3, boiling at 102°, and iso- CH \ propvl iodid, ^'^•■'^CHI, boiling at 89.5°. Thco- LH3/ retically, there are four monohalogen derivatives of butane, of which two are produced from normal Initane: CH3 — CH, — CH3 — CH.X and CH3 — CH, — CHX — CH3. while the other two are produced from isohulanc: CH3. CH3 VH—CH^X and VX-CHj CH3/ CH3/ Tertiary butyl iodid, (CH3)3CI, is prepared l)y treating isobutyl alcohol with sulfuric acid and dis- 258 PHARMACEUTIC CHEMISTRY. solving the so-produced isohutylene in concentrated hydriodic acid; thus: CH3 CH3^ >CH— CH3OH = CU/ CH3/ CH3 CH3, ■ )C=CH, + HI= ■ )CI-CH3 CH3/ CH3/ Another method is b_\- healing triniethxlcarhinol with HI; thus: (CH3),,C — OH + HI = (CH3)3CI + H^O. SUMMARY OF THE HALOGEN DERIVATIVES OF THE HYDROCARBONS. The inorganic compounds of a metal with a hydroxyl group are called bases and resemble each other closely, owing to their common constituent — the OH group. Alcohols, on the other hand, are organic compounds, although, like the inorganic bases, they possess the OH group and, like the latter, combine with acids to form water. Inorganic example: NaOH + HI = NaT + H,0 sodium hydroxid sodium iodid Organic example: C2H5OH + HI = C,,H,I + H.,0 ethyl hydroxid ethyl iodid The products so formed are comparable with the salts of inorganic chemistry and are commonly known as "compound ethers" or cslrrs. As bases (an lose water, formiiii: ;iiih\ (bids or oxids, so also ALKYL HALIDS. 259 can the alcohols. Thus, by abstracting one molecule of water jrom two molecules oj an alcohol, "ethers" are formed. If two alcohols are employed, "mixed ethers" are formed. If an alcohol is treated with a halogen acid, alkyl halids are formed which have been called "halid ethers." Thus, ethyl chlorid, CH3CI; ethyl bromid, CjHjBr; propyl iodid, C3H7I, have been termed halid ethers. Preparation. — All the alkyl halids may be pre- pared by a similar reaction (Gay-Lussac, 1835); that is, by acting with a phosphorous halid on a corresponding alcohol, which yields the correspond- ing alkyl halid and phosphorous acid; thus: 3CH3CH2OH + PBrg = 3CH3.CH2Br + H3PO3. Properties. — Like the inorganic halids, some of the alkyl halids slowly precipitate silver nitrate solu- tion; some, however, do not react with it at all. The alkyl halids can be converted into one another. For example, if ethyl chlorid is heated with potassium iodid, ethyl iodid can be produced. CHAPTER XXIV. THE HYDROXIDS OF THE HYDROCARBON RADICALS, OR ALCOHOLS. Among the several classes of the oxygen derivatives of the hydrocarbons are the alcohols, ethers, aldehyds and the acids. These may be said to be the most important classes and all the others to be derivatives of these. Alcohols are formed when one or more h\dn)gen atoms of a hydrocarbon is replaced by the corre- sponding number of hydroxyl ( — OH) grou{)s. .Alco- hols are classified in two ways: (a) According to the number of hvdroxvl groups they contain; thus, alcohols containing one hydroxyl group arc called monatomjc or monacid; those containing two hydroxyl groups are called diatomic or diacid; those containing three hydroxyl groups are called triatomic or triacid, etc. Usually, alcohols containing more than two hydroxyl groups are termed polyatomic or polybasic alcohols. (6) According to their structure; thus, when the hydroxyl is linked to a carbon atom which is combined with only one other carbon atom, the alcoliol is known as a prim.iry alcohol, and contains the univalent primary alcohol group ■ — C'H.^OH. Primnry alcohols when oxidized yield aldchyd (lud an acid. When the hydroxyl is linked to a car- bon atom which is united with two other cari)on 260 O X o u X + c Methyl Alcohol Ethyl Propyl Butyl Pentyl (Amvl) Alcohol Hexyl Alcohol Heptyl " Octvl Cetyl Ceryl Myricyl " U ^^^^xxx ^xxxxx^xxj%%% CJ U U'U U U CJ U CJ u CO + c Methyl Ethvl Propyl Butyl Pentvl (Amyl) Hexyl Heptyl Octyl Cetyl Ceryl Myricyl < M ^. ^, ^ ::; s -s £ffi ffi ffi m m K E % % \ U U U U U CJ U CJ CJ u u' O P3 u o Pi Q >^ X + W c U Methane Ethane Propane Butane Pentane Hexane Heptane Octane Hexadecane Hexacosane Triacontane CJ CJ tJ"CJ CJ U U U U CJ CJ 262 PHARMACEUTIC CHEMISTRY. atoms, the alcohol is known as a secondary alcohol, and contains the divalent secondary alcohol group = CH()H. Secondary alcohols when oxidized yield ketones and acids. When the hydroxyl is linked to a carbon atom united with three other carbon atoms, the alco- hol is known as a tertiary alcohol containing the trivalent tertiary alcohol group =COH. Tertiary alcohols when oxidized yield compounds containing fewer carbon atoms. Preparation of the Alcohols. — Alcohols may be formed in several ways: (i) By the action of moist silver oxid upon the alkyl halids; thus: (a) CH3I + AgOH = CH3OH + Agl methyl alcohol (b) C2H5I + AgOH = C3H ,QH + Agl ethyl alcohol (c) C3H,I + AgOH = CgH.OH + Agl propyl alcohol (2) By the saponitication of the esters. The decom- position of esters by boiling with alkali hydroxids is usually spoken of as "saponification " with reference to its similarity to the decomposition of fats; thus: CHa C^ H^O a + KOH = CH3OH + KC7H,03 methyl salicylate methyl alcohol (3) By treating primary amins with nitrous acid; thus: NH2CH3 + NO.OH = CH3OH -t- K, + H,() (4) By the fermentation of fruit juices containing sugars or other carbohydrates: QH,20„ + ferment = 2C2H5OH + 2CO, sugar a'cohol PROPERTIES OF THE ALCOHOLS. 263 The production of alcohol by the fourth method will be fully discussed under Ethyl Alcohol. General Properties oj Alcohols. — The alcohols are colorless, neutral substances, among which those con- taining but few carbon atoms are liquids, while the higher members are solids. The lower members have also a distinctive odor, a burning taste and arc soluble in water. These three characteristics — taste, smell and solubility — diminish with the increase in molecular weight. Thus, the first three members are readily miscible with water — butyl alcohol dis- solves in 13 parts, amyl alcohol in 40 parts, and so on. The proportion of oxygen present seems to influence its solubility. Thus, cetyl alcohol, CjgHgjOH, which can be prepared from sper- maceti, is a water-insoluble solid, very similar to paraffin wa.x. Chemical Properties. — The structure of alcohols is shown by several reactions: (i) When alcohols are treated with alkali metals, hydrogen is liberated and a compound of the hydro- carbon and the metal is formed. Thus, if methyl alcohol is treated with metallic sodium, the metal is dissolved, and upon evaporation a white, hygroscopic solid is obtained, known as sodium methylate (methoxid), CHgONa. When ethyl alcohol is treated in the same manner, a similar compound is obtained, known as sodium ethylate (ethoxid) or, more commonly, sodium alcoholate, QH^ONa. In view of the fact that, immaterial to the quantity of the metal employed, onlv one atom of hydrogen is 264 I'lIARMACKUTlC- CHEMISTRY. replaced by it, it indicates strongly that only thi- hydrogen of the hydroxyl group is rejilaced 1)\- the sodium, and thus proves the structure of the alcohols: rH,()H + Na = CH.ONa + H. (2) Alcohols combine with acids, neutralizing them and forming water, in which reaction they are distinctly suggestive of the behavior of the metallic hydroxids; thus: 2CH3OH + H.SO, = (CH3),S(), + 2B.,(). (3) When treated with phosphorus jx^ntachlorid alcohols form alkyl chlorids, hydrochloric and l)hosphoric acids. An examination of the following reaction will show that one chlorin atom replaces the hydroxyl group in the alcohol, which is very similar to the action of the same reagent upon water; thus: 4CH3OH + PCI5 = 4CH.,n + HCl + PO(OH)3, corresponding to 4H2O + PCI5 = 5HCI + PO(OH)3. A characteristic property of all the alcohols is their tendency to form neutral compounds willi the acids. These neutral, salt-like bodies are called "ethers" or "esters"; and when oxidized, the alcohols form acids containing two hydrogen atoms less and one oxygen more than the corresponding alcohol. METHYL ALCOHOL, carl)inol, wood alcohol, wood naphtha, wood spirit, methyl hydroxid, CH3OH. Properties. — Pure methyl alcohol is a colorless liquid, with odor and taste similar to ethyl alcohol. It boils at 66.7° and has a specific gravity of o.S. It closelv resembles ordinar\- alcohol in all of its DISTILLATION OF WOOD. 265 properties and is used in its stead as a solvent for fats, oils, resins, etc. It burns with a nonluminous flame; taken internally, it intoxicates, and in concen- trated form it is highly poisonous. The crude wood alcohol has a disagreeable odor, reminding one of acetone. The purified varieties are marketed under such fanciful names as "Eagle Spirits," "Colonial Spirits," "Columbian Spirits," etc. In Great Britain a tax-free, methylated spirit is employed in the arts; it is a mixture of lo parts of crude methyl alcohol with go parts of common alcohol. Preparation. — Methyl alcohol (from meth, wine, and ule, wood) is obtained by the destructive dis- tillation of wood. (Boyle, 1661.) When wood is subjected to destructive distillation without access of air, it yields inflammable gases, an aqueous, strongly acid distillate, some tar, and the residue is wood charcoal. The operation is carried out in large iron retorts, and the products may be summarized as follows: Gases, 25%. / Carbon raonoxid, dioxid, methane < Noncondensable. \ acetylene, ethylene and propylene. y gy [ Acetone, furfurol, methyl alcohol, ^iPOi'S 5°/o- . I methylamin and acetic, formic, butyric, crotonic, capronic and Condensable acid "^"^ ■ [ propionic acids. Tarry liquid, 10%. f Creasote, toluol, xylol, cumol, methol, creasol, phlorol, naphthalin, pyrene, '^' [ chrysene and paraffin. Residue, 15%. Charcoal and inorganic salts. The aqueous distillate contains methyl alcohol mixed with acetic acid, acetone and methyl acetate. This mixture is known as pyoligneoiis arid and sepa- 266 PHARMACEUTIC CHEMISTRY. rates from the tarry liquid on standing, when it is decanted. It is next neutrahzed with lime, whereby the acetic acid is converted into lime acetate. This mi.xture is then subjected to distillation. The volatile methyl alcohol and acetone, together with water, pass into the receiver and form the crude wood spirit. This is further purified by fractional distillation over quicklime, which separates the greater part of the acetone which has a lower boiling- point (56°). Lately, wood alcohol has also been produced by subjecting the by-products of the beet- sugar industry to destructive distillation. The molasses is fermented and the ethyl alcohol is removed by distillation. The solid residue is then dried and distilled like wood (see description in previous paragraph). ETHYL ALCOHOL, ethyl hydroxid, "grain alcohol" or comm(m alcohol (alcohol U. S. P.), C^HjOH. Ethyl alcohol is obtained by the fermentation of certain carbohydrates, most i)articularly glucose with yeast (vinous fermentation, also called alcoholic fermentation). It has been shown that fermentation may be caused by the presence of small organisms, either of vegetable or animal origin, known as fer- ments. There are several kinds of ferments. The one causing alcoholic fermentation is zymase, a vegetable ferment contained in ordinary yeast. These ferments are sometimes called enzyms and are divided into organized and nonorganized ferments. These include i)cpsase (pepsin), the enzym of gastric juice; trvpsasc (tryi)sin). the cn/.yni of the pancreatic FERMf:NTS. 267 juice; diastase, found in malt; amylopsase (amvlop- sin), found in pancreatic secretion and similar to diastase; invertase, found in yeast, hydrolyzes sucrose to a mixture of dextrose and levulose (invert sugar) ; synaptase, from seeds of the rose order, converts amygdalin into benzaldehyd, hydrocyanic acid and sugar; myrosase (myrosin) exists in both the mustard seeds and hydrolyzes the albuminoids present therein, forming allyl sulfocyanid (volatile oil of mustard) ; papayotase, found in the juice of papaw (carica papaya), converts proteids and starch into soluble compounds; bromelase (bromelin), found in the juice of pineapple fruit, digests pro- teids; rennase (rennin), found in the gastric juice of the fourth stomach of the calf, coagulates milk, rendering some caseinogens soluble, while precipi- tating others: these are respectively known as "wheys" and "curds"; catalase, found in tobacco leaves, is an oxidizing enzym which causes fermenta- tion in fresh tobacco leaves, and is productive of the so-called "bouquet of tobacco," which is absent in the fresh leaves. As there are different kinds of ferments, they also cause different kinds of fermentation with different products. The principal kinds of fermentation of interest to the pharmaceutic student are the alcoholic or vinous fermentation, produced by a vegetable ferment, zymase, which is found in ordinary yeast. The products of its action are alcohol and carbon dioxid. Acetic Fermentation.'— T\ns is caused by a peculiar 268 I'lfARMACEUTIC CHEMISTRY. vegetable ferment (mycoderma aceti) which acts upon alcohol, converting it into acetic acid. Lactic Fermentation. — This is caused by a vegetable ferment (bacterium acidi lactici) contained in sour milk, which has the power of converting sugar into lactic acid. The germs of various ferments are found in the air, and under favorable conditions they develop and produce their characteristic changes. Such fer- ments develop, for instance, in a solution of grape- sugar, commonly known as glucose, and if this con- tains any nitrogenous body which is essential to their development, they will convert the glucose into alcohol and carbon dio.xid. The ordinary sugar, which we call "cane-sugar" or "sucrose," is not directly fermentable. It must first be converted by a nitrogenous substance, which is known as "invertase" and whichis invariably a constituent of yeast, into grape-sugar, or glucose, and fruit-sugar, or fructose. This change may be expressed in the following reaction: C,,W,,0,, + H,0 = CeH,30„ -h CeH^^. cane-sugar grape-sugar fruit-sugar. The above chemical change or decomposition, in which the elements of water were added to effect the reaction, is known as hydrolysis. Invertase, there- fore, is a "hydrolytic ferment " or "enzym." Either of these two sugars so produced (fructose and glucose) are directly fermentable with yeast, forming the alco- hol and by-products. It may be added that the reaction expressing the formation of alcohol from ALCOHOL MANUFACTURE. 269 glucose is not as sim])le as it may appear at first sight; for, in addition to the alcohol and carbon dioxid produced, two amyl alcohols are produced which, together, constitute the "fusel oil"; propyl and isobutyl alcohol, a little succinic acid and about 2.5% of glycerin are formed at the same time. Manufacture of Alcohol and Beverages. — The grain, which may be either maize, rye, rice, oats, potatoes or other starch-rich fruits (molasses is frequently used) is ground to a meal and macerated in water at a temperature between 85 and 88° C. This process is called "mashing," in which the starch is changed into soluble form, such as dextrose or maltose. This, upon the addition of malted barley or rye, at a tem- perature of 60° C, is converted by the action of diastase into glucose. This liquid is cooled to about 18 °C., yeast is added and the glucose is broken up into carbon dioxid, which is evolved and escapes, and alcohol, which remains in the liquid. Other products formed at the same time are, as said before, propenyl, propyl, isobutyl and amyl alcohols, to- gether with succinic acid. These latter are less volatile; that is, have a higher boiling-point than the ordinary alcohol, which is obtained by fractional distillation. This distillation is best conducted in a "columnar still," best known as "Coffey's still." The ordinary alcohol, besides the admixture of the above alcohols, also contains much water, from which it may be separated b}- fractional distillation. It, boiling at 78° C, is separated from the water readily, while the fusel oil is separated partly by distillation. 270 PHARMACEUTIC CHEMISTRY. and the last traces of it by filtering the alcohol through animal charcoal. Animal charcoal has the property of absorbing foreign odors and the process is, therefore, known as "deodorization." The water cannot, however, be completely removed b\- redistillation, though a product containing about 96% of alcohol may be obtained by that process. Absolute alcohol is prepared from ordinary alcohol by removing the water from it by means of some dehydrating agent, such as quicklime or anhydrous copper sulfate. Thus, by repeated treatment with lime, the water can be reduced to 0.5%, and this small quantity can be further removed by treatment with metallic sodium. The commercial varieties of absolute alcohol contain about 99%. The Pharma- copoeia recognizes three forms of alcohol — the ordi- nary alcohol, containing 92.3% by weight or 95% by volume of absolute alcohol; the absolute alcohol (alcohol absolutum U. S. P.), which should contain not more than 1% by weight of water; and the diluted alcohol (alcohol dilutum U. S. P.), containing 41% by weight or 49% by volume of absolute ethyl alcohol. Tlie requisites jor successjul jcnticntation are (1) Glucose, loo.o parts (2) Albuminoids, i.o parts (3) Mineral salts. 0.5 parts (4) Yeast, 0-5 parts 102.0 j)arts (5) Air, at the outset. (6) A temperature between 5 and 30° C ALCOHOLIC BEVERAGES. 27 I And the products of fermentation may be tal)ulated as follows: (i) Ethyl alcohol, 48.5 parts (2) Carbon dioxid, 46.5 parts (3) Glycerin, 3.6 parts (4) Succinic acid, 0.7 parts (5) Fusel oil and extractives, 0.7 parts (6) Yeast, increased to 2.0 parts 102.0 parts (7) Traces of organic esters which give the fer- mented product its "bouquet." Beer Manujadure. — Barley is moistened with warm water, strewn upon warm floors and allowed to germinate (sprout) . During this process a ferment, called diastase, is developed which converts part of the starch into sugar. The barley is now dried quickly to prevent further growth, and it constitutes the so-called " malt." This malt is ground to a meal and placed in water at about the temperature of 76° C, to allow the diastase to act on the unaltered starch. The liquid is then strained and is now called " wort," to which hops are added to give it the bitter taste and flavor. Yeast is now mixed and the fer- mentation is allowed to proceed to a certain point, but never to a completion. The yeast is then sepa- rated and the beer is drawn off into casks and subjected to high chilling "vatting," in which process the yeast which remains floating, deposits and becomes dormant. The best process for fer- mentation is dependent upon the correct mainte- 272 I'll AKMACKITIC (.11 KMIS TRN . nance of the tem])eratuix'. Thus, in the I'niled States, a tempeniture of between 15 and 16" C. is maintained, and the same may be said of Great Tiritain, while in France and Germany the tempera- ture is not j)ermitted to exceed 12° C. Good beer should not contain alcohol in excess of 3%, and bock beer in excess of 4' , . Lager. — This is a beer brewed at a temperature between 5 and 10° C. This low temperature keejjs the yeast at the bottom and hence the fermentation is much more com])lete. Lager contains between 5 and 7% of alcohol. Ale. — In the manufacture of ale the temperature is maintained comparatively high — between 15 and 30° C. The bubbles of carbon dioxid rise and carry the yeast to the surface, forming there a thick stum. This mechanically checks the Oxidation and hence the fermentation. After the ale has been drawn ott into the casks the fermentation starts up again and continues for some lime. Whisky Maniijacture. — Whisky is usually made from corn, but frequently from r\e, wheat, potatoes or other starch-bearing vegetables". The grain is ground to a meal and mixed with water and' a very little mall. This latter furnishes the diastase nec- es.sary to (omerl the starch into sugar. This mix- ture, called "mash,"' is kept at a warm temperature until all the starch has been acted upon. The liquid is then drawn off and mi.\ec said to be the fermented juice of grapes. When grapes are expressed and with their skins permitted to stand at a temperature not exceeding 30° C, they ferment, giving rise to red wines. If the juice, however, has been strained off from the skins before the fermentation sets in, white wines will be the product. If fermentation is per- mitted to proceed to almost completion, "dry" wines are obtained. These are subjected to distillation and all but al)out •]^\ of their alcohol is removed by dis- r8 274 PHARMACEUTIC CHKMISTRV. tillation. The alcohol so removed possesses a flavor and a bouquet peculiar to itself, and when obtained from champagne grapes is termed "cognac"; but when obtained from the ordinary grape it is termed "brandy." Brandy is, therefore, the liquor obtained by distilling wine (spiritus vlni gallici U.S. P.), con- taining from 46 to 55% of alcohol by volume, and at least four y^ars o'.d. When the fermentation is not permitted to continue to completion, sweeter wines are produced. These sweeter wines, of which port, angelica and sherry are the types, contain upward of 18% of alcohol, whereas the dry wines, such as claret or hock, contain 7 and 9%, respectively. Rum is made from molasses by fermentation and distillation. Gin is made by macerating crushed juniper ber- ries in 60% alcohol and then subjecting to distillation. Other beverages, such as porter, which may be said to be "evaporated beer," we shall not treat of. DECAY. — It is well known that many moist organic substances when exposed to the air undergo a slow process of oxidation, and so are gradually destroyed without sensible rise of temperature.- This process of slow combustion or oxidation differs from fer- mentation, and is called decay. Properties oj Ethyl Alcohol.— VA\^\\ alcohol is a colorless, transparent, mobile liquid of a character- istic agreeable odor and burning taste. It boils at 78° C. and has a specific gravity of 0.809 (25° C). It is miscible with water, ether, chloroform and, with the exception of water, it is the most generally employed solvent in pharmacy. It is one of the best ADULTERATION OF ALCOHOL. 275 solvents for resins, alkaloids, essential oils, camphor, iodin and many organic and inorganic compounds. It does not dissolve the fixed fats. It is very in- flammable. Its most common impurity is aldehyd. The presence of aldeh}d is detected by the addition of silver nitrate which produces discoloration; oak tannin in presence of potassium hydroxid T. S. gives a brownish-yellow color. When 25 c.c. of- alcohol are evaporated spontaneously, the barely moist sur- face of the dish should not be colored red or brown, with 5 drops of concentrated H2SO4 which shows the absence of fusel oil and organic impurities. Chemical Properties oj Ethyl Alcohol. — Alcohol may be detected by warming it with a little iodin and potassium hydroxid, when crystals of iodoform will separate and can be identified by their smell and crystalline form. With chlorin it forms chloral, and with bleaching powder and water, chloroform. With strong nitric acid it evolves ethyl nitrate. When it is mildly oxidized, it is converted into acetaldehyd; and if subjected to strong oxidation, it is converted into acetic acid. With chromium trioxid alcohol ignites spontaneously and burns to carbon dioxid and water. When treated with sulfuric acid, it forms ethyl sulfuric acid, commonly known as " sulfovinic acid." If, however, an excess of alcohol is heated with sulfuric acid, ether is formed by the abstraction of water, the acid simply acting as a dehydrating agent. Adulteration of Ethyl Alcohol and Alcoholic Bever- ages. — Frequently, for the purpose of reducing the cost of beverages and more frequently in reducing 276 PHARMACEUTIC CHEMISTRY. the cost of remedial agents for external application, and of those given in but small doses, part or all of the ethyl alcohol is substituted by methyl alcohol. In the first instance it is sophistication; in the second instance, substitution. To detect the presence of ethyl alcohol in such mixtures the following method can be employed to advantage: The alcohol or a solution of it is subjected to distillation and the portion distilling between 60 and 80° is collected. A spiral of copper wire is heated to redness and plunged into the liquid several times, after which it is filtered. One drop of a 0.5% aqueous resorcinol solution is added, and the mixture is floated upon concentrated sulfuric acid. A rose- red zone at line of contact indicates ethyl alcohol; a scanty white or ])inkish coagulum appears directly above the zone and finally separates and rises in purplish flakes (similar reactions are given by the tertiary butyl alcohols and formic acid, l)ut the suc- cession of colors and the deportment of flaky coloring matter are different). Nomenclature 0} the Alcohols. — It is sometimes desirable to consider all of the alcohols as derivatives of methyl alcohol — Carbinol. This greatly facilitates the naming of the alcohols. Thus: Carl)in()I is methvl alrohol, CH,()H Methyl carbinol is ethyl alcohol, CH.CH.OH Ethyl carbinol is propyl alcohol, ("JUCIIX^H Dimethyl carbinol is isopropvl alcohol, CII ;C'TI()IICH , IVopvl carbinol is butvl alcohol, (-,H,CH.,C)H Trimelhyl carbinol is 'isobuty! alcohol, (CII,),C()H Isopropyi carbinol is primary isobiityl alcoiiol, CH^CII.-OH Isomerism amoiii^ the Alcohols. — Tlic possibili- OXIDATION OF ALCOHOL. 277 ties of isomerism among the alcohols arc even greater than among the hydrocarbons. Thus it may arise in thi-ee ways: ((/) by branching of the carbon chains; (b) by changing the position of the hydroxyl group; (c) or through both of these simultaneously. Thus, while methyl and ethyl alcohols have no isomers, there are two propyl alcohols, the normal and the iso-; four butyl alcohols; eight amyl alcohols, etc. TJie Propyl Alcohols. — Normal propyl alcohol has a boiling-point of 97.4° and may be separated from fusel oil by fractional distillation, while iso- propyl alcohol boils at 82. 7° and is obtained by acting on acetone with sodium amalgam. The following are the graphic formulas of the two propyl alcohols: CH3 I ■ CH3CH3 CH, \/ I . CHOH CHjOH isopropyl alcohol, normal propyl alcohol The following are the graphic formulas of the four butyl alcohols: CHj CH3 I CH3C3H 1 CH3CH3 CH. \/ CH. \y I CH I COH CH. I - CHOH I J, C H^OH I CH3 CH^OH isobutyl ^^3 tertiary butyl normal butyl alcohol secondary butyl alcohol alcohol alcohol The Eff eels oj Oxidation Upon the Alcohols. — It has been said that primary alcohols upon oxidation yield aldehyd, and when subjected to still further oxida- 278 PHARMACEUTIC CHEMISTRY Specific gravity at 20% 0.804 0.789 0.810 0.806 0.786 0.815 0.81b Boiling- point. 00 0000 0000 0^0 t^« t^Ot^r^ 00"COCN(Nr^N', (2) /sobutylcarbinol, (3) Secondary butyirarbinol, (4) Methyipropylcarbinol, (5) Methyi/sopropylcarbinol, (6) Diethycarbinol, (7) Dimcthylethylcarbinol, (8) Tertiary butvlcarbinol, SECONDARY ALCOHOL. 279 tion, they yield acid^ demonstrate this fact: CH, I H- -c : H + o I : o :H alcohol CH3 + o The following reactions CH3 H— C +H.O O acetaldehyd CH, ! OH \/ c=o_ acetic acid acetaldehyd The secondary alcohols in the first stage of oxida- tion also lose 2 atoms of hydrogen, but the resulting compounds are termed "ketones." Thus secondary propyl alcohol (iso-) upon oxidation yields dimethyl ketone, commonly known as acetone. Ketones upon further oxidation split up into acids having fewer carbon atoms, carbon dioxid and water. The following reactions illustrate this: CH3CH3 C H. O H + isoprophyl alcohol. CH, I C =0 + H,0 I CH., CH, CH, dimethyl ketone (acetone) C^ I CH, :0 + 2O, dimethyl ketone + CO., + H,0 OH acetic acid 28o IMIAKMAC KITIC CUKMISTRY. When tertiary alcohols are oxidized they form ke- tones or acids with fewer carbon atoms than the original alcohol containetl. Thus the tertiar\- butyl alcohol containing 4 carbon atoms splits uj) into dimethyl ketone (containing three carbons), carbon dioxid and water, as the following reaction illustrates: CH3 CH^ I ■ I H,C-C-(3H + 2 0. = C = + C02 + 2H.,0 I " i ' ■ CH3 CH3 The nature of the alc(,)hols may be determined by still another process than the oxidation method. The oxidation method is somewhat tedious and a "color-test diagnosis" has been recommended. (Victor Meyer. ) The alcohol is converted into alkyl halid by treat- ment with red phosphorus and iodin; the iodid is dried with calcium chlorid and then distilled with silver nitrite. A nitroparaffin is obtained which is mixed with potassium nitrite and dilute potassium hydroxid. Dilute sulfuric acid is next" added drop by drop. If this plroduces a red color it indicates a prinnry alcohol; a blue color points to ^secondary; while no coloration indicates a tertiary alcohol. (This test is sometimes called "the red, blue and white test.") AMYL ALCOHOL, pentyl alcohol, C.,H„OH. This alcohol derives its name Irora amylum, starch. Two of its eight isomerids constitute the so-called AMYL NITRITE. 28 1 fusel oil. Fusel oil is a mixture of the secondary butyl carbinol and isobutyl carbinol, has a character- istic, unpleasant odor and is not miscible with water, but floats upon it like an oil, from which it derives its name " fusel oil." Fusel oil is obtained from high wine, but the glucose obtained from potato starch yields a considerably greater amount of it, and hence amy] alcohol is sometimes known as "potato oil." Properties. — Commercial amyl alcohol is an oily, yellowish licpiid which, ' when oxidized, yields valeric acid. AMYL NITRITE, CsH^jNOa, is prepared by a process similar to that employed in the making of ethyl nitrite; that is, by distilling a mixture of the alcohol, sodium nitrite and sulfuric acid. Amyl nitrite is a highly aromatic substance, has a low boiling-point and should consist of at least 80% of isoamyl nitrite (amylis nitris U. S. P.) AMYL ACETATE, CjHn— CoHgO,. This ester is prepared bv distilling a mixture of amyl alcohol, sodium acetate and sulfuric acid. It constitutes the jargonelle pear essence. Mixed with methyl alcohol and benzin, it constitutes the so-called "banana oil" of the painters, used to suspend aluminum and gold l)ronzes for painting. AMYLENE HYDRATE, ethyl dimethyl carbinol, is used as a hypnotic (CH3)3C. CHjOH. On oxida- tion it yields only acetic acid: CH3. .OH cn/ ^CH, — CH 3 amylene hydrate CHAPTKR XXV. DIATOMIC ALCOHOLS OR GLYCOLS. The alcohols of the olefins or the ethylene series are all diatomic or diacid. They contain two hydroxyl groups in the molecule, they are heavy and viscid, reminding one of glycerin, and hence the name "glycols" is applied to the group. The glycols are not very interesting to the pharmacist. Properties. — The glycols can be easily prepared from the dihalogen derivatives of the olefins by the action of water and a metallic oxid in much the same way as the monatomic alcohols are obtained by treating the alkyl halids with an alkali; thus: CjH.CI, + 2KOH = r.,H,(OH), + 2KCI. ethylene glycol The glycols are colorless, viscid liquids with a high boiling-point. Thus, ethylene glycol boils at 195° C. They are all very soluble in water. The glycols exhibit all the properties of the alcohols, but doubly. Thus, ethylene glycol contains two primary alcohol groups, and. by successive oxidation of these groups to aldehyd and carboxyl groups, the following series of products should be derivable. However, only the second, third and fifth have been obtained from glycol by oxidation. (i) (2) (3) (4) (5) CH.OH CH.OH Clio CHO COOH CHO coon CHO coon cooh glycoilic glycollic glyo.xal glyoxallic oxallic acid aldehyd acid acid 282 ETHYLENE OXID. 283 Among the more interesting compounds of ethylene glycol the following may be mentioned: When hydrochloric-acid gas is passed into glycol, one of its hydroxyls is replaced by the chlorin, form- ing a chlorhydrin and splitting off water. When, however, glycols are treated with phosphorus pentachlorid, both hydroxyls are replaced, and ethylene chlorid is formed; thus: (i) CH,.OH 1 " + HCl = CH,.OH CH,.C1 = 1 " +H,0 CH^.OH (2) CH,.OH 1 " + 2PCI. CH..OH ethylene chlorhydrin CH2.CI = 1 + 2POCI, + 2HCI CH,.C1 ethylene chlorid When caustic alkalis act upon chlorhydrins, "ethylene oxids " are formed: CH2.CI CH.. I + KOH =1 )0 + KCl + H.O CH2.OH C H/ ethylene oxid When ammonia gas acts upon ethylene chlorid, it replaces the chlorin with two amido groups and forms diamin: CH..C1 CH,.NH, I " + 4NH3 = I " + 2NH,CI. CH.Cl CH^-NH, ethylene diamin This is a primary diamin, with basic properties of the amins. 284 I'UARMACKUTIC CHLIMISTRV. Choliii, nciirin, laiirin, may all be said to be derivatives of eth}lcne glycol; thus: CH,OH Cl\2 CII,.NH,\ ! - _ 11 -.1 • )o CH,N:(CH,)3.0n CH.N:(CH,)3.Qli CH..SOa/_ cholin neurin taurin ChoJin is found in the brain and egg-yolk, forming with glycerol, stearic and i)hosphoric acids a com- plex compound — lecithin {C^^ Hgg N3O9P). Neu- riii is a product of the putrefaction of albumin, and classed among the ptomaines. 2\iurin is a constit- uent of bile. The second of the oletinic alcohols is a/Zy alcohol CH2 = CH — CH2OH. It is derived from the second member (propylene) of the olefin hydrocar- bons, and is prepared by heating isopropylene, allyl iodid (C3H5I) with water at 100°. The isothiocy- anate of this alcohol constitutes the essentuil oil of mustard, and the sultki constitutes oil oj i^arlic: CH,\ CH— N = CH,/ S li =c muslai d black CH, H,C 1 '\ / "1 CH — S — H C 1 / \ 1 allyl isothiocyanate In nature, the oil of by macerating grouni CH, - H2C allyl sulfid d (essential) is obtained mustard seeds with cold water and distilling the product with steam. The potassium myronate — a glucosid of the seeds — is fer- mented by myrosin, an enzym present, and the oil, glucose and potassium bisulfate are formed; thus: Q„H.„NS20,K 4- H2O = C3H =N = C = S + C„H,20„ + KHSC),. ^"yl isothiocyanate. TRIATOMIC ALCOHOLS OR GLYCERINS. 285 TRIATOMIC ALCOHOLS OR GLYCERINS. As the monatomic alcohol CHjOH corresponds to the inorganic hydroxid NaOH, and the diatomic glycol C2H4(OH)2 to the inorganic calcium hydroxid Ca(0H)2, so do the triatomic alcohols, as glycerin, C3H5(OH)3, correspond to ferric hydroxid, Fe(OH)3. GLYCERIN, glycerol, propenyl alcohol, is a clear, odorless, colorless, sweet liquid, having the specific gravity 1.246 and a boiling-point of 290°. It cannot be distilled alone, but it is readily distilled with superheated steam under reduced pressure. It is very hygroscopic, neutral, and dissolves in water and alcohol, but is insoluble in chloroform, benzol and the fixed oils. It was discovered by Scheele (1779), who isolated it while making lead plaster; and Chevreul found it to be the constituent of natural fats and oils. It can be prepared from fats by saponification, by decomposing these with caustic alkalis; also by passing superheated steam through a fat. This last method is the one most commonly used in the manufacture of glycerin. Glycerin does not freeze until about — 17 °, and for that reason it is valued in gas meters and automobiles which must be exposed to low temperatures. Large quantities of it are employed in the manufacture of glyceryl nitrate (nitroglycerin), from which, in turn, dynamite is made. In pharmacy it is used as a solvent. Its graphic formula shows it to be composed of three alcoholic groups, of which one is secondary and two are primary: OF THE UNIVERSITY OF 286 THARMACEUTIC CHEMISTRY. CH2.OH I CH.OH I CH2.OH glycerol = C3H3(OH)3. Chemical Properties oj Glycerin. — When heated with sulfuric acid, acrolein is formed, which is recog- nized by its odor. It liberates boric acid from borax. With chlorin it forms mono-, di- or tri- chlorhydrins: CH2CI CHjCl CH,C1 CHOH ► CHCl > CHCl I I I ^ CH.;OH ^H^Cl^ CHX'l monochlorhydrin dichlorhydrin trichlorhydrin Glycerin should not reduce Fehling's solution, showing the absence of glucose (its frequent adulter- ant). Glycerin dissolves coloring matters, tannin and extractives, and may be called an "intermediate " solvent between alcohol and water. It increases specific gravity of fluid extracts and tinctures, pre- venting their precij)itation. Structure. — The structure of glycerol has l)een determined by several syntheses, of whi\h the following one may be given as an example: CH3 CH3 CH, CH,v I — I _ I -^ )CHOH— 9M^9^ COOH c = o CH,/ alcohol acetic | isopropyl alcohol acid CH, GLYCERIC ACID. 287 CH, CH3 CHj.Cl CH2.OH II I I CH — . CHCl — . CH.Cl — CH.OH II I I I CH, CH.Cl CH,.C1 C H,.OH propylene propylene 3 chlor- glycerol dichlorid hydrin When acetone is reduced, isopropyl alcohol is formed which, when heated with sulfuric acid, forms propylene. Propylene, in turn, combines with chlorin, giving propylene chlorid which, when treated with iodin chlorid, is converted into trichlorhy- drin. Trichlorhydrin, heated with water to 170°, yields glycerol : CH2CI HOH CH^OH CHCl + HOH = CHOH + 3HCI. I I CHXl HOH CH^OH When glycerol is reduced with hydrogen, the secondary group is attacked, giving rise to dioxy- acetone, CH^OH — CO — CH^OH. AUyl alcohol (found in oil of garlic), when oxidized with potas- sium permanganate, yields glycerol. The trivalent radical of glycerin is sometimes termed "glyceryl." When one of the primary alcohol groups is oxidized, CH2OH I glvceric acid— CHOH — is formed. Upon further I CO.OH oxidation, the second primary alcohol group is affected, and tartronic acid is formed. W'hen dioxyacetone is treated with caustic soda, it is con- 288 PHARMACEUTIC CHEMISTRY. verted into glyceric aldehyd, which condenses with part of the dioxyacetone, giving rise to an artificial sugar which, chemically, is an inactive fructose (a-acrose), to which the name aldol has been given. .\ldol may be synthetized as follows: CH,.OH CH.,OH CH,.OH CH^OH i I ' I I CH.OH + C = = CH.OH C = i III CHO CH.OH CH.OH CHOH _^ __ " I I >j;lyceric dioxyacetone aldol _ C,.H,.,0 aldehyd " i- '' Manitj ictiD-c of Glycerin.— (i) By superheating stearin with water: C3H5 (C,,U,,0,), + 3%0 = 3HQ8H35O2 + tristearin stearic acid C, H- (OH) 3. glycerin (2) As a by-producl in the manufacture of soap. When fats are boiled with an alkali hydroxid, soaps are formed and glycerol is set free : C.7H35COO— CH, KOH Cx7lI,,sCO()lv CH.OH Cz7H3,COO— CH + KOH = CivHj.CQOK + CHOH C.7H,.COO-CH, KOH C,^H,„COOK CH.OH tristearin potassium ttearate glycerin. (soft soap) From the above it will be seen that soaps — scdium or j)()tassium oleate or stearate — arc sails oj the jalfy acids. Potassium stearate is very deliquescent. It takes up water from the air and is, therefore, termed "soft soap"; sodium stearate is not de]i(iuesi-ent and constitutes the hard soaps of the market. Some NITROGLYCEROL. 289 salts of these acids, such as calcium or magnesium, are insoluble in water, and they must all be precipi- tated before the soap will act as a detergent. This is the reason why the use of soaps in laundering is attended with great waste of soap. Hard waters for laundry purposes may be rendered soft by precipi- tating these compounds and decanting the so-softened water. One method of accomplishing this is to add about one grain of alum per each gallon of water, stirring it well and letting it stand for some little time, when the aluminum hydroxid and carbonate formed therein will slowly subside, carrying with it all of the inorganic "hardening salts" in solution, in the water. Glycerol forms salts with nitric acid, of which the trinitrate is the most important. Trinitrin, nitroglycerin, glonoin, Nobel's oil. C3H5(ON02)3. Trinitrin was discovered by Sobrero (1841), but was first applied practically by Nobel (1867). Nitroglycerin is prepared by mixing 12 parts of fuming nitric acid v/ith 20 parts of sulfuric acid, and running into this well-cooled mixture a very thin stream of glycerol, which is forced in by a current of air. The sulfuric acid serves here as a dehydrating agent: C3H,(OH)3 + 3HNO, = C3H,(ONQ J3 -f 3H2O. trinitrin The mixture is diluted with water, the nitrogly- cerin separates in oily drops or layer, which is care- fully washed with water to separate the glycerin, and next with a weak solution of soda to free it from 290 PHARMACEUTIC CHEMISTRY. the acids. It is then converted into the manv ex- plosive compounds. This highly explosive compound has the ap])ear- ance of a yellowish oil, which is highly volatile. By warming nitroglycerin carefully and dissolving in it collodion-cotton (nitrocellulose); upon cooling, the mixture solidifies to a jelly-like consistence. This jelly is insoluble in water and is well adapted to many purposes where explosives are required. It is called explosive gelatin or blasting gelatin. Dynamite is made by mixing 3 parts of nitrogly- cerin with I part of a fine silicious earth, such as kieselguhr, which is very porous and which can absorb considerable quantities of nitroglycerin with- out becoming pasty. This mixture is moulded into cartridges or sticks and fired by a detonator, usually made of mercury fulminate. When gun-cotton and nitroglycerin are made into a pulp with acetone and a little petrolatum, cordite is formed. This pulp is squeezed through small holes into tiny threads which, upon evaporation of the acetone, are used after being cut up for smokeless rifle cartridges. When mixed with sawdust, nitrate of potassium or ammonium nitrate, various exj^losivcs are formed which are known under such names as jorcite, vitlcan powder, etc. The method of manufacture of trini- trin is similar to the formation of ethyl nitrate from ethyl alcohol, and, like the latter, it can be saponified by caustic alkalis, showing that in fact it is an ester and not a nitro comj^ound. The name nitroglycerin, therefore, is only used because througii usage it has THE FATS. 291 been adopted as the technical name of the compound, but in fact it is a misnomer. Nitroglycerin is official in the Pharmacopoeia as a spirit (spiritus glycerylis nitratis U. S. P.), which contains 1% by weight of nitroglycerin. THE FATS. In constitution the fats resemble nitroglycerin in that they are esters of the higher fatty acids. Thus, olive oil, cottonseed oil and expressed almond oil are chiefly glyceryl esters of oleic acid; palm oil is chiefly glyceryl of palmitic acid; beef tallow is nearly pure glyceryl stearate, while castor oil is glyceryl ricinoleate; expressed oil of nutmeg (nutmeg butter) is chiefly glyceryl myristicate. Again, expressed laurel oil is glyceryl laurinate and butter is glyceryl butyrate. These glyceryls are the proximate prin- ciples of these various fats and are collectively known as fats. The important fats are: Laurin, C3H5(Ci2H,302)3, its acid = HC12H23O2 = lauric acid. Myristin, C3H5(Ci,H.,70,)3, its acid = HCi.H^.O^ = myristic acid. Palmitin, C3H5(C\eH3iO.,)3, its acid = HCigH3iO = palmitic acid. Olein, C3H5(Ci3H330,)3, its acid = UC,,U,,0, = oleic acid. Stearin, C3H5(Ci,H3,(),)3, its acid = HC,sH3502 = stearic acid. Liquid fats consist almost entirely of olein; olive oil, cottonseed oil and expressed oil of almonds are 292 IMIAKMACKUTIC CHKMISTKV. examples of pure olcin. They are sometimes called fatty or fixed oils, to distinguish them from the es- sential, volatile or ethereal oils. Solid fats contain a larger proportion of palmitin and stearin; it might be said that the relative pro- |K)rtion of each of the three glyceryls (palmitin and stearin are solids, olein a liquid) ]>resent in the fat determines its consistency and other ])hysicai properties. CoDiposition. — The animal fats consist })rincipally of a')out 8o'/o <^>f the glyceryl esters of the higher fatty acids (stearic, palmitic and oleic) and about 2o9c of th'e esters of the lower fatty acids and sometimes the esters of the higher alcohols. The proportion of these esters varies with the sources of the fats. Properties. — The solid fats melt below 100° C. and can be distilled at about 300° C. with a slight decomposition. At higher temi)eratures they are decomposed into acrolein. When pure they are colorless, odorless and tasteless. They are insoluble in water, sparingly in cold alcohol, but freely in ether, chloroform, benzene and carbon disulfid. They all have a lower specific gravity than water. Upon standing, by a decomposition peculiar to the fats alone and due perhajjs to oxidation or fermentation (and maybe to both), fats ac(juire color and taste. These are, therefore, products of decomposition. The disagreeable odor and taste of fats (rancidity) is due to the fatty acid which is liberated. Such rancid fats, when heated with sodium carbonate solution, are der)rivcd of their disagreeable oflor. I'RKPARATIOX AND ADULTERATION Ol' J ATS. 293 The liquid fats all have a specific gravity lighter than water, but when exposed to lower temperatures, they become partly solid (lard oil), and through such reduction of temperature some of the principles may be separated from the others. Preparation. — Animal fats are prepared from the tissues by melting them alone or in the presence of water and separating the fused fat by straining. Many of the vegetable oils are prepared by expres- sion, sometimes by extraction with a volatile solvent, such as petroleum benzin, carbon tetrachlorid, etc., while inferior oils are obtained by boiling the material with water, decanting the floating oil from the refuse matter and straining. Adulteration. — Fats are very prone to adulteration with commoner or cheaper varieties. Owing to the similarity in composition, the adulterants are difficult to detect. The principal means of detection of the fraud is by the odor, which is peculiar upon warming, by the color reaction with acids or silver nitrate and by the boiling- and melting-points. Fish oils (a frequent adulterant) are detected in the vegetable oils by passing chlorin gas through the oil. In the presence of jish oils, the fat will turn dark. Sulfuric acid, when heated with ten parts of the oil, produces different colorations, depending on the nature of the oil, and serves as a means of identifying the same. Thus, with oil of black mustard, a bluish-green color is acquired; with fish oil, a reddish color; and with linseed oil, a dark brown. The identity and purity of fats may be determined quantitatively by the 294 PHARMACEUTIC CHKMTSTRY. "saponification value." This dc])ends upon the number of cubic centimeters of alcoholic potash required to neutralize a weighed quantity of the oil. The other test is the determination of the "iodin number," which depends on the determination of the percentage of iodin solution absorbed by the fat. In the case of vegetable fats, the presence of pro- tein or mucilaginous substances tends to rancidify them. These impurities may be removed by filtra- tion or by treatment with 2% sulfuric acid. The acid is gradually added to the fat in which it carbon- izes the impurities and, after separating the acid and repeated agitation with water to wash away the last traces of it, the fat is subjected to filtration. Fats should be preserved in perfectlv dry, her- metically sealed vessels and in a cool place. Beef tallow, mutton suet and lard are mixtures of stearin, palmitin and olein. In the first fat, stearin predominates; and in the last fat, olein. Butter is a complex mixture .of the glycerids of butyric, caproic, caprylic, capric, myristic, palmitic and stearic acids. The first four of the above esters constitute about 12% of butter. They are volatile with water vapor and can be separated from the other constituents of butter by distilling with steam. Butter is made from the cream of cow's milk by the process of churning. When of good quality, it should contain about 90% of fat, 8% of water, 1% of curd and 1% of salt. As said before, butter consists mainlv of stearin, with about 7''-' of l)Ut\rin. The BUTTER MANUFACTURE. 295 purity of butter may be roughly determined by saponi- fying a weighed quantity with caustic soda, acidify- ing with sulfuric acid and distilling. The volatile fatty acids which distill over are estimated by titration with alkali hydroxids. The water is determined by drying a weighed sample of butter n a hot-water oven to a constant weight. The salt and curd may be determined by melting and passing through a weighed filter, washing the filter with ether until free from fat. The curd and salt remain upon the filter, and the salt is estimated by igniting the filter, burning off the organic matter, and the curd by difference. Old, rancid butter may be deprived of its rancidity by heating it and treating with a solution of sodium carbonate and afterward by kneading it with sweet milk, which latter serves two purposes: first, to wash away the traces of the alkali present, and, second, to impart a sweet-milk flavor to the butter. Such is the method of making "renovated butters." Renovated butters may be readily detected by heating them slightly in a test-tube, when the rancid odor will at once appear; and upon higher heating, a frothing will occur with a peculiar, crackling sound. Since, as an article of diet, butter is rather high- priced, many so-called "butter substitutes " have been offered. Of these margarin, oleomargarin, butterin and cottosuet are the familiar commercial examples. These are prepared by melting beef tallow or suet and heating to a temperature of 35° and subjecting to pressure. The lower melting portion, which is expressed, contains a large quantity of olein, to which 296 PHARMACEUTIC CHEMISTRY. the name "oleo oil" has been gi\en. This, wlu-n mixed with eottonseed oil and a little milk and genuine butter, upon chilling, constitutes oleomar- garin. The butter substitutes can be identitied by the fact that the volatile fatty acids (butyric acid) are always considerably below that of the genuine butter (4-5-5 %)• The melting-points of the two articles also vary considerably. When properly prepared, margarin is a perfectly wholesome article of food and in chemical composition ver\- similar to butter. Wool-jilt, also called wool-grease, Yorkshire grease, and its purilied varieties, known under the fanciful name of "lanolin" (adeps lanae, and adeps lan^e hydrosus U. S. P.), constitute the oflacial fat from sheep's wool. It is prepared by scouring wool Chemically, it is a complex mixture of the fatty acids with cholesterol, an alcohol having the formula ^6^44^- It is separated from the wool washings by adding sulfuric acid, which causes the "cracking," or raising the greasy matter to the surface, when it is skimmed off. It comes into the market in a brown, semi-solid mass which, upon trituration with water, forms a straw-colored emulsion known as the hy- drated wool-fat or " lanolin." The cholesterin is capa- ble of absorbing more than its own weight of water, it resists saponification and does not rancidify. It has also the property of penetrating the skin and is, therefore, preferable to the other unguents. Cacao butter, obtained by expressing roasted chocolate nuts, is known in [)harmacy as a yellowish-colored fat. LIQUID FATS AND THE WAXES. 2Q7 melting at 30 to 35 °C. to a clear liquid, and having a specific gravity of 0.97. Chemicall}-, it is a mix- ture of olein, palmitin, stearin, arachin and laurin. It is used for making suppositories and ointments (oleum theobromatis U. S. P.). Liquid fats are classified into: {a) Drying oils; this group embraces poppy, linseed, hemp and nut oils. {b) Nondrying oils; olive, almond, rape, colza, lard, tallow and neatsfoot oils. (The first four are vegetable.) (r) Inte'rmediate oils (which possess some prop- erties of each of the above two classes. These embrace codfish oil, cod-liver oil, sperm, hake, por- poise, shark and whale oils. This is the so-called fish-oil group. To the cottonseed oil group belong cottonseed oil, sunflower, beechnut and teel oils. Besides, the two alcohol-soluble oils — castor oil and croton oil, are classed here. All oj the above fats when saponified yield soaps and glycerin. The Waxes.— This is a division of the fats consisting of those which, on saponification, yield no glycerin, but do yield complex, monatomic alcohols. All waxes are solid at the ordinary temperature, and they include beeswax, which may be bleached by exposing it to light; Chinese- wax, Brazilnut wax, myrtle wax, palm wax and spermaceti, the last obtained from deposits in the head cavities of the sperm-whale. Manufacture of Candles. — Stearic acid, which we commonly call stearin, is used in the production of 298 PHARMACKUTIC CHEMISTRY. candles. After tristearin is hvdrolyzed with su])er- heated steam, pure stearic acid is obtained, this after separation from glycerin, is afterward pressed while hot to remove the liquid oleic acid, and to produce the harder and firmer stearic acid. Stearic acid, after mixing with a little paraffin wax, is moulded into candles. Sometimes paraffin wax with a mixture of but a trace of stearic acid is used for the same purpose. Varnishes. — Among the drying oils, pop]\v oil and linseed oil were mentioned. These oils, when ex- posed to the air, oxidize slowly, forming a hard varnish. The absorption of oxygen from the air by these oils can be made to take place much more rapidly; thus: By boiling the drying oils with lead oxid, manganese dioxid or oxalate, these take up all of the oxygen and are converted into "boiled oils," also called "quick-drying oils." When linseed oil is boiled with resins or "varnish gums," as they arc sometimes called, such as kauri gum, copal gum or dammar gum, varnishes are produced. Wirnishes are sometimes thinned by turpentine, benzin or alcohol. Allied Products. — As glycerin is a ])roduct of the fats, so allyl alcohol is also a product of glycerin. When glycerin is heated with oxalic acid, two of the OH groups are removed, according to the following formula: C3H5(()H)3 + (COOH), = C3H,— OH +2C(X allyl alcohol + 2H..O. ACROLEIN. 299 giving rise to allyl alcohol, to whicli the following graphic formula has been ascribed: CH. II ' CH I CH,OH When allyl alcohol is subjected to further oxidation, the remaining primary alcohol group is oxidized and an aldehyd called acrolein is formed: CH.. II " CH I O K ^H Acrolein is a liquid possessing a pungent odor and is a constituent of the acrid fumes from burning fat. When acrolein is subjected to oxidation, acrylic acid is formed, to which the following graphic formula has been ascribed: CH OH When all three hydro.xyl groups of glycerin have been replaced by oxidation with COOH groups, 300 I'HARMACKUTIC CHKMISTRY. Irkarhallylic acid, to which the following graphic formula has been ascribed, is formed: CH,.COOH 1 CH.COOH I CH2COOH This acid is chemically interesting from the fact that its hydroxyl derivative, which has also been obtained from glycerin, is the very important citric acid. CITRIC ACID, HaCeH-O;, exists naturally in the fruits of the members of the orange family, such as lemons, limes, oranges, etc. Mail II fact 11 re 0} Citric Acid. — On a large scale, the lemon peel is.first grated off and from it, by solution with petroleum ether, oil of lemon is obtained. The lemons are then sliced, their juice expressed and sub- jected to boiling. In the process of boiling the al- buminous and mucilaginous principles are coagulated and can be removed by filtration. To the filtered aqueoussolution lime-water is added, which neutral- izes the juice and forms calcium citrate. By adding to the solution of calcium citrate sulfuric acid, the salt is decomposed and citric acid is liberated. It is then subjected to filtration to free the liquid from the insoluble calcium sulfate. The liquid is further evaporated to a small bulk and permitted to crystal- lize. Citric acid should be carefully examined for the presence of calcium sulfate and free sulfuric acid Other Polyatomic Alcohols.— Besides glycerin, an- other triatomic alcohol is known, namely, pentcnyl ARTARIC ACID. 301 alcohol, C5H9(OH)3, also called amyl glycerin. Eryfliritol, C^Hg(OH)„ is a tetratomic alcohol found in certain lichens. It is of little importance, but the dibasic acid corresponding to it is very important. TARTARIC ACID is a dibasic and diatomic acid and exists in four different physical modifications. The chief difference in these modifications is found in the crystalline form of the salts produced from them and in the behavior of their solution when viewed with polarized light. The four kinds of tartaric acid known are: (i) Dextrotartaric acid (the acid in ordinary use). (2) Levotartaric acid. (3) Racemic acid (a mixture of equal weights • of the dextro- and levo- modifications ; inactive, but efflorescent). (4) Mesotartaric acid (inactive, and obtained by heating the ordinary dextro acid with a small quantity of water) . The graphic relations of the four acids may be shown by the following structural formulas: (i) ' (2) (3) (4) COOH COOH COOH COOH I i I I CHOH CHOH HOHC HOHC I - I - I - I CHOH HOHC CHOH HOHC I I 'I I COOH COOH COOH COOH When speaking of tartaric acid we said it was 302 I'lfARMACEUTIC CHEMISTRY. dibasic and diatomic. The basisity of an organic acid is reckoned by the number of the carboxyl ( — COOH) groups it contains, while the atomicity of an acid is reckoned by the number of hydro.wl ( — OH) groups it contains in addition to the carboxyl groups. Thus, we observe that the tartaric acids contain in their graphic formulas two carboxyl and two hydroxyl groups and are, therefore, dibasic and diatomic, while citric acid contains three carboxyl groups and one hydroxyl group and is, therefore, spoken of as tribasic and monatomic: (COOH) CH(OH) CH2(C00H) C(OH) (COOH) CH(OH) (COOH) A dibasic diatomic acid (tartaric) CH2(C00H^ A tribasic-monatomic acid (citric) (The different groups will be found in i)arentheses.) Tartaric acid occurs in nature chiefl\- as impure potassium bitartrate, or cream of tartar, commercially known as argols. It is deposited during the process of fermentation in the form of a brown, crystalline crust, also called "wine-lees." It was ist)lated by Scheele (1769), and is found widely distributed in fruits. With malic acid it is found in the berries of mountain ash, and is also found in gooseberries, raspberries, strawberries, its main source being grape juice. When gra|)C' juice is subjected to fermentalion, the alcohol whicli forms in the process renders the PREPARATION OF TARTARIC ACID. 303 potassium salt of tartaric acid insoluble, and this deposits in minute crystals on the sides and bottom of the vat. The brown powder dissolved in water, filtered through bone-black, the solution evaporated and allowed to crystallize, constitutes "cream of tartar." Both tartaric acid (acidum tartaricum U. S. P.) and potassium bitartrate, "cream of tar- tar" (potassii bitartras U. S. P.), are official; the first is required of 99.5%, the latter, 99% purity. • Tartaric acid is prepared from argols by dissolving it in water and neutralizing with chalk. The insol- uble calcium tartrate which deposits by filtration is separated from the neutral potassium tartrate which remains in solution. The solution, by being treated with calcium chlorid, gives a further yield of the acid. The entire process is represented in the following equations: (i) 2KHC,H,Oe + CaCOg = CaC.H.Og + KjC.H.Oe + CO, + H^O. (2) K^C.H.O, + CaCU = CaC,H/:», + 2KCI. The solution of calcium tartrate is next decomposed by sulfuric acid, filtered from the insoluble calcium sulfate, concentrated by evaporation and allowed to cool, when crystallization will take place. The potassium chlorid is recovered as a by-product and employed in the manufacture of potassium salts. Tartaric acid occurs in large prisms, is freely soluble in water and alcohol and has a melting-point of 135 ° C. When subjected to dry distillation, pyro tar- / /;7V(/r/rf— (methyl succinic acid,) CH^— CH(CX)OH) — CH,(C()OH)— is formed. 304 IMIARMACEUTIC CHEMISTRY The official salts of tartaric acid are "Rochelle salts" and "tartar emetic." Rochelle salt is chemically potassium and sodium tartrate — a double salt occurring in transparent prisms or a white powder, soluble in 1.2 parts of water. It is prepared by adding cream of tartar to a solution of sodium bicarbonate. The operation should be carried on carefully, owing to the evolution of carbon dioxid gas, until the first solution is neu- tralized. It is next filtered, evaporated and allowed to crystallize. The following reaction takes place: KHC,H,0, + NaHCOj = KNaC.H.Og + CO, 4- H,0. Rochelle salt (potassii et sodii tartras U. S. P.) is an ingredient in the official compound effervescent pow- der (seidlitz powder). It is sometimes called "Seig- nette's salt" after its discoverer, Seignette de la Rochelle. Tartar emetic (anlimonii et potassii tartras U. S.P.) is the potassio-stibyl tartrate, an acrid salt, crystal- lizing with half a molecule of water; soluble in water and prepared by dissolving antimonous oxid in a solution of cream of tartar: Sb,0 , -f 2KHC4H4O6 = 2KSbOC4H,06 -1- H,0 potassio-stibyl tartrate. COOK I CHOH = I CHOH I COO-^Sb = Tartar emetic is a stroiiLr poison. The best anti- BAKING POWDERS. 305 dote is tannic acid or any substance containing it. Baking Powders. — These usually are mixtures of cream of tartar with sodium bicarbonate and starch or other dry material which serves the purpose of a 'iiUer" and acts as an absorbent of any moisture, thus preventing the liberation of any free carbon dioxid. The baking powder is added to flour and stirred with water, forming dough. This operation liberates the carbon dioxid which, in the process of baking, is evolved, making the bread porous and spongy. The reaction which takes place is identical with the one exhibiting the formation of Rochelle salt. Since sodium carbonate is harmful, its excess in baking powders should be carefully avoided. A good baking powder can be made by carefully drying cream of tartar and sodium bicarbonate and mixing these with starch in the following proportions: cream of tartar, 4; sodium bicarbonate, 2; starch, ^ part. Alum is sometimes found a constituent in commercial baking powders, this in the presence of sodium bicar- bonate forms the injurious and insoluble aluminum hydroxid with the evolution of carbon dioxid. Alum baking powders should be guarded against. Calcium diphosphate with sodium bicarbonate frequently forms the addition to the so-called "self- rising" flours. The reactions of the three classes of baking potvders : (i) Cream of tartar with a bicarbonate reacts thus : KHC.H.O^ + NaHCOg = NaKC^H.O, + H,0 -f CO2. Rochelle salts being formed. 3o6 PHARMACiaiTlC CHKMISTRY (2) Alum powders react as follows: 2AlK.(SO,)2 + 6NaHC03= K,SO,+ 2Al(OH)3 + 3Na2SO, + 6CO,. Aluminum hydrate and sulfates of sodium and potassium being formed. (3) The acid-phosphate powders react as follows: CaH,(POj, + 2NaHC()3 = CaHPO, + Na,HPO, + 2H,0 + 2CO2. Hydrocalcium phosphate and sodium jjhosphate are produced in the reaction. Arahitol and Xylitol, C5H7(OH)5, are both pen- tatomic alcohols, both obtained by reducing their corresponding aldehyds; arabinose, a constituent of gum arable; and xylose, a wood gum obtained from various trees by digestion with caustic alkali and precipitation with alcohol. /\mong the hexatomic alcohols are classed mannitol, dukitol and sorbitol, CgHg(OH)g, all found in the different species of ash; they all contain a straight chain of carbon atoms. Synthesis oj the Alcohols.— {1) Methyl alcohol may be synthetized by treating methyl halid with potas- sium hydroxid: CH3I + KOH = CH3OH + KI Ethyl alcohol may be synthetized from its elements as follows: (a) C2 + H2 = C2H2 = acetylene. (b) C2H2 + H2 = C2H, = ethylene. (c) CjH, 4- H2SO, = C2H5HSO, = ethyl sulfuric acid. id] alcohol. SYNTHESES OF THE ALCOHOLS. 307 (2) Ethyl alcohol may be produced from methyl alcohol by converting the latter with phosphorus iodid into a methyl halid, two molecules of which treated with two molecules of potassium hydroxid split into two molecules of potassium iodid, water and ethyl alcohol; thus: (a) 3CH3OH + PI3 = 3CH3I + P(OH)3. {b) 2CH3I + 2KOH = 2KI + H2O + C2H5OH. A third method of synthesis is by converting the alkyl halids with potassium cyanid, which reaction yields alkyl cyanids, called nitrils. When a nitril is treated with zinc and hydrochloric acid, it is reduced to ethyl-amin. This can be diazotized by treating with nitrous acid, yielding ethyl alcohol, water and nitrogen, as follows: {a ) CH3I + KCN = CH3— C = N, methyl cyanid, + KI. (b) CH3CN +, Zn, + 4HCI = CH3CH2NH,, ethyl amin, + 2ZnCl2. (f) CH3CH2NH2 + HNO2 = CHgCHjOH, ethyl alcohol, + N, + HjO. This reaction is a very important one in that we may pass from a one-carbon-atom compound to a two-atom-carbon compound, and from a two-carbon to a three-carbon compound, etc. By this method of synthesis we can build up very complex compounds from simpler ones. Methyl cyanid may be obtained directly by heating ammonium acetate with phosphorus pentoxid, and for this reason it is frequently called aceto-nitril. Secondarv and tertiary alcohols mav be svnthetized 3o8 PHARMACEUTIC CH li.MISTRY. as follows: When acetaldehyd is heated with zinc alkyl. compound, the zinc atom of the latter attaches itself to the oxygen atom by one bond, losing at the same time an alkyl group which, in turn, is trans- ferred to the unsaturated carbon atom of the same group. The ])roduct is subsequently decomposed with water, forming the alcohol; thus: CH3CHO + Zn(CH,), = CH3 — CHO H — CH 3 + acetaldehyd secondary propyl alcohol ZnO + CH,. When ketones are treated with zinc alkyl com- ])ounds, tertiary alcohols are formed; thus: CH, I C H,— C( ) --CH ,+Zn(CH,), = CH;-^C— OH+ZnO+CH, dimethyl ketone | CH, tertiary biitvl alcohol. ■ Secondary alcohols may also he synthetizcd by means of the magnesium alkyl compounds by what is known as "Grignard's reaction." When an alkyl bromid or iodid reacts with magnesium in the l)resence of ether, correspontling magnesium alkyl l)romid or iodid is formed. Thus: .\ig + cH,i = y^g^j^' magnesium methyl iodid The magnesium alkyl compounds are decomposed by water and form paraffins. With aldehyds ketones and esters, etc., when decomposed with FORMATION OF SFXONDARY ALCOHOLS. 309 water, they form secondar)- and tertiary aUohols and ketones; thus; /CH3 (i) CH3CHO + CH3MgI = CH — CH ^O Mgl intermediate magne- sium compound /CH, • /CH, (2) HOH+CH3— CH =CH3— CH +Mg( \ \ \OH ^OMgl ^OH secondary propyl magnesium alcbhol oxiodid CHAPTER XXVI. THE CYANOGEN COMPOUNDS. CYANOGEN, C,N, (from kyanos, blue, and gennao, to generate, due to the fact that some of the double cyanids possess a brilliant blue color), was first prepared by Gay-Lussac, who made it by heat- ing either mercuric or silver cyanids: (i) Hg(CN), = Hg + (CN), mercuric cyanid (2) 2AgCN = Ag.. + (CN), silver cyanid Cyanogen is a colorless gas with a characteristic odor resembling thaf of the essential oil of hitter almonds; it is very solul^le in water and very poison- ous. It is combustible, burning with a pink flame, producing carbon dioxid and free nitrogen. Its specific gravity is 26 and its formula {C'N)^ is often written Cy. Te:it. — The odor of the gas and the peculiar pink color of the flame serve as the best means for the recognition of cyanogen. Dissolved in water, it forms a very poisonous acid which in its dilute form — 2% strong — is official (acidum hydrocyanicum dilutum U. S. P.). It is prepared by fi eating ])otassium cyanid witli dilute sulfuric acid; thus: 2KCN + H,S(), = 2HCN + K,S(),. 310 POTASSIUM I'ERROCYANID. 3II This acid was first discovered by Scheele (1782), who prepared it from Prussian blue by distilling it with a mineral acid. He correspondingly called it "prussic acid," which, however, contains 4% of the anhydrous acid, and is, therefore, twice as strong as the official dilute acid. In cases of poisoning the best antidotes are mild inhalations of ammonia or chlorin, the application of cold water to the head and spine and the ingestion of the following solution in the order named: (i) Potassium carbonate, 20 grains in a fluid ounce of water; (2) ferrous sulfate, 10 grains in a fluidounce of water, and tincture ferric chlorid, i fluidram; the object of the above order being, first, to form potassium cyanid; second, the ferrocyanid and, third, the ferric ferrocyanid (insoluble). Upon standing HCN decomposes into ammonium formate: HCN + 2H2O =HCOO. NH,. POTASSIUM FERROCYANID, yellow cyanid of potash, yellow prussiate of potash (potassii ferrocy- anidum U. S. P.), K,Fe(CN)6, 3H2O. This is pre- pared by heating potassium carbonate free from sulfate and introducing a mixture of iron filings and charcoal obtained from refuse matter rich in nitrogen (evaporated blood, horse hair, hoofs or horns). When the carbon dioxid and inflammable gases cease to be given off, the liquid mass is poured out, cooled and lixiviated with water. The resulting solution is crystallized, the crystals redissolved in water and repurified by recrystallization. DESCRIPTION AND PROPERTIES.— The salt occurs in large, lemon-vellow, soft, translucent 312 PHARMACEUTIC CHEMISTRY (T\stals; odorless, with a sweet saline taste, neutral reaction and slightly efflorescent; soluble in four parts of water, insoluble in alcohol. Tests. — Ac^ueous solutions of the salt with ferric chlorid give dark blue precipitates (Prussian blue); with ferrous salts, bluish-white precipitates are formed which gradually turn greenish-blue; with copper salts, chocolate-brown precipitates, and with lead acetate, \vhite precipitates are formed. The salt should not effervesce with dilute sulfuric acid (carbonates) ; wdth hydrochloric acid and barium chlorid, only slight cloudiness (limit of sulfates). Fused with potassium nitrate and dissolved in water, filtered and the filtrate treated with silver nitrate, it should give but slight white precipitate (limit of chlorids). POTASSIUM FERRICYANID, red prussiate of potash, K3Fe(CN)8. This salt is made by the reduction of potassium ferrocyanid with chlorin; thus: 2K,Fe(CN)„ + CI., = 2K3Fe(CN)e + 2KCI. A solution is made of potassium ferrocyanid, the chlorin passed into the liquid changes "its color from yellow to red. It is tested from time to time with ferric chlorid, and when it ceases to produce a blue color with it, it is concentrated by evaporation and crystallized. On exposure to air the salt decomposes into ferrocyanid. The salt is not official and is only valued as a test solution, producing with ferrous salts a dark blue precipitate (TurnbuU 's blue) ; with copper salts, a brownish-yellow precipitate; with silver IROiV I'ERROCYANIl). 313 salts, orange precipitates; with mercurous salts, reddish-brown; but no precipitates are formed with either ferric, mercuric or plumbic salts. IRON FERROCYANID, Prussian blue, William- son's blue, Paris blue, Fe,(Fe(CN)6)3. This salt, while not official, is of technical interest. It is prepared by double decomposition between potas- sium ferrocyanid and a ferric salt, washing and drying the precipitate: 3K,Fe (CNje + 2Fe2(SO,)3 = Fe,(FeCN6)3 + 6K,SO,. It is also made on a large scale by precipitating ferrous sulfate with potassium ferrocyanid and ex- posing the bluish precipitate to the air till it oxidizes and acquires color of proper depth. POTASSIUM CYANID (potassii cyanidum U. S.P.). Tw^o varieties of this salt are known in commerce— (i) the commercial cyanid, which is used for photo- graphic purposes, and made by fusing dried potas- sium ferrocyanid with potassium carbonate, decanting the semiliquid mass from the sediment of iron and allowing it to cool and solidify. The potassium cyanate, which is a by-product in this reaction, is dissolved out with carbon disulhd. The second method for the production of (2) pure potassium cyanid is by neutralizing hydrocyanic acid with potassium hydroxid. This is most con- veniently done by passing HCN gas into an alcoholic solution of potassium hydroxid: ist method: 2K,Fe(CN)6 + 2K2CO3 = loKCN-f- 2KCNO + Fe.. + 2 CO.,. 314 PHARMACEUTIC CHEMISTRY. 2d method: HCN + KOH = KCN + H,(). Potassium cyanid occurs in white, opaque, amor- phous pieces or granular powder; odorless when dry, deliquescent in air, emitting the odor of HCN. It is soluble in 2 parts of water, sparingly in alcohol. It should be 90% pure; is strongly alkalin, usually con- taining 10% of a carbonate. It is used in the arts as a solvent in the manufacture of polishing agents; in the electroplating industries, also for the extraction of gold and silver from the rocks with which it forms soluble compounds. It is a strong poison. SILVER CYANID (argenti cyanidum U. S. P.), AgCN, is prepared by precipitating silver nitrate with potassium cyanid; thus: AgNOg -fKCN = AgCN + KNO3. The salt should be 99.9% pure, which corresponds to 80.48% of metallic silver. It is a white, odorless and tasteless powder, permanent, but gradually turning brown, and should be preserved in the dark. It is insoluble in water, alcohol or cold nitric acid, but souble in boiling nitric acid, evolving HCN. It is also soluble in ammonia water, potassium cyauid and sodium th osulfate solution. The only use made of the salt is for the extemporaneous preparation of the official dilute hydrocyanic acid, which is done by mixing silver cyanid, 6 parts, witli mixture of hydrochloric acid, 5, and water, 55 parts, agitating until all of the silver chlorid precipitates and pouring off the solution of HCN. The reaction is as follows: AgCN + HCl = HCN + AgCl. AMMONIUM SULFOCYANID, NH.C^NS, ammo- POTASSIUM SUI.FOCYANID 315 nium thiocyanate, is made by dissolving carbon disulfid in alcohol and heating in the presence of ammonia, according to the following reaction: CS, + 2NH3 = NH.CNS + H^S. This salt is very analogous to the following: POTASSIUM SULFOCYANID, KCNS, potassium thiocyanate. This salt may be prepared by fusing together potassium ferrocyanid and sulfur: K,Fe(CN)« + 3S, = 4K(CN)S_+ Fe(CNS)2. potassium sulfocyanid The fused mass is next boiled with a solution of potassium carbonate which converts the ferrous sulfocyanid into potassium sulfocyanid and ferrous carbonate, which latter precipitates: Fe(CNS)2 + K2CO3 = 2K(CN)S + FeCOg. The soluble sulfocyanids can be prepared by direct union of the soluble cyanids with sulfur, as follows: NH.CN + S = NH.CNS. Potassium sulfocyanid is present in minute quanti- ties in the human saliva. Tests. — With ferric chlorid, the sulfocyanids give a blood-red coloration, which is not discharged by strong hydrochloric acid, thus distinguishing it from the red ferric acetate. POTASSIUM CYANATE, KCNO. This may^be prepared by exposing fused potassium carbonate Tor some time to the air; the salt absorbs oxygen from the air and is converted into the cyanate: 2KCN + O, = 2KCNO. 3l6 PlIAKMACiaTlC Clll^MISTRV. The salt can also be prejjared by adding lead oxid to fused putassium cyanid; the potassium salt unites with the oxygen of the lead, forming the cyanate and setting the metal free. AMMONIUM CYANATE, NH.CNO, a very soluble salt, which can be prepared by mixing a solution of potassium cyanate and ammonium sulfate. A double decomposition takes place, forming potassium sulfate in addition to the ammonium salt. This, upon the addition of alcohol, precipitates the potassium sulfate, leaving the ammonium cyanate in solution: 2KCNO + (NHJ2SO, = 2NH,CNO + K2SO,. This salt is very interesting chemically, because it is isomeric with urea, CO(NH2)2. Urea can be prepared from ammonium cyanate by simply evapo- rating its solution to dryness on the water-bath. It is evident, therefore, that boiling water is sufficient to rearrange the atoms in the molecule; on the other hand, urea may be reconverted into ammonium cyanate by heating it to dull redness. When this is done, cvanuric acid forms and ammonia gas is given off: 3CO(NH,,), = H3C3N3O3 + 3NH3. cyanuric acid If cyanuric acid is heated more strongly, it splits into cyanic acid, which distills over: H.,(;,N3()3 = 3HCNO. cyanic aciii If, now, the cyanic acid be neutralized with the ammonia previously evolved, ammonium cyanate is reproduced. THE ETHERS. 317 Other organic compounds of nitrogen tvill be dis- cussed in a special chapter. THE ETHERS. (R-O— K) Molecular Boiling- Specific formula point gravity Dimethyl ether CaHftO 23.6° Diethyl ether C4HI00 K-6° o"73i ( 4°) Dipropyl ether . . C6HI40 go. 7° 0-763 ( 0°) Di-isopropyl ether C6HX40 69° 0-743 ( 0°) Di-normal-butyl ether.. . CsH.sO 141° 0-784 ( 0°) D''-secondary-butyl ether CsHisO 121° 0-756 (21=) Di-isobutyl ether CsHxsO 122° 0-762 (15°) Di-isoamyl ether CoH^.O 170° 0-799 ( 0°) Di-normal-ortyl ether. . . C,6H340 280° Melting- point 0-805 (17°) Dicetyl ether C,.H660 55° As has been shown, alcohols correspond to the inorganic alkali hydroxids. Similarly, it may be stated that ethers correspond to metallic oxids. The ethers are formed by replacing the hydrogen of the hydroxyl of an alcohol -with an alkyl. The compound ethers may be formed by a similar intro- duction of an acid radical or by replacing the hydro- gen of the carboxyl of an acid with an alkyl. Mixed ethers, on the other hand, are oxids of two different alkyls; thus: Simple ether is ethyl oxid, CjH^ — O — CjH^. Compound ether (or ester) may be represented by ethyl acetate, CH3COOCH,,. 310 I'HARMACELiTIC CHEMISTRY. Mixed ether may he represented by methyl-ethvl ether, CH3OC2H5. Preparation. — (i) Simple ethers. These may be prepared by treating an alcohol with an alkali metal and the resulting compound with their halogen derivative of a hydrocarbon. Thus, methyl ether may be prepared as follows: (i) CH3OH + K = CH3OK + H. potassium ethylate (2) CH3OK + CH3CI = (CH3),0 + KCl. Ethyl ether, "sulfuric ether," ethyl oxid, is the ordinary ether (aether U. S. P.). This is the common ether as we know it. It can be formed when sodium ethylate is warmed with ethyl halid. This is the "synthesis of Williamson," which not only indicates the formation of ether, but also its structure: C2H30Na + QHJ = C2H5— O— CoHs + Nal. Ethyl ether is prepared on a large scale by heating alcolol with dehydrating agents, such as sulfuric acid; thus, if we abstract from two molecules of alcohol one molecule of water, ether rfesults, accord- ing to the following ecjuation: 2C2H5OH = C2H5OC2H5 + H2O. It can be prepared by heating a mixture of 5 parts of 90% alcohol and 9 parts of concentrated sulfuric acid in a flask provided with a thermometer and a dropping funnel and connected with a condenser. When the tciupcrature rises to 140°, the mi.xture will CONTINUOUS ETHER PROCESS. 319 begin to boil and ether distills over. Alcohol is now slowly run in from the dropping funnel, the tempera- ture at the same time being carefully regulated to 140-145°, until a considerable quantity of the ether passes over. The liquid in the receiver may be said to be a crude mixture of ether, alcohol and water, and in addition it contains sulfur dioxid which is produced by the decomposition of the acid. This is shaken with dilute soda in a separatory funnel, the layer of ether which floats on the surface is carefully separated and distilled from quicklime and purified by redistilling from a water-bath. The ether so prepared is about 90% pure and contains traces of alcohol and water. These are removed by adding pieces of bright metallic sodium, allowing to stand for several hours and again distilling. Sodium ethylate and hydroxid remain behind and pure ether passes over. The ether, in order to answer the re- quirements of the Pharmacopoeia, must be at least 96% pure. The reaction described above is known as the "continuous ether process"; that is to say, with a given quantity of ether which serves there as a dehydrating agent only, unlimited quantities of ether should be prepared. As a matter of fact, a comparatively small quantity of the acid transforms a very large quantity of the alcohol, but the process has a limit in that the acid finally becomes diluted with the abstracted water and a part of it is reduced with the formation of sulfur dioxid. The reaction really takes place in two stages: first, the alcohol is converted into ethyl hydrogen sulfate (sulfovinic 320 PHARMACEUTIC CHEMISTRY. acid), this compound next interacts with alcohol, yielding ether and sulfuric acid; thus: (i) QHjOH + H,SO, = QHs — HSO, 4- H,0. ethyl hydrogen sulfate. (2) (UIjHSOj + QH.OH = QH,— O— C.H. + H.,S(),. Properties. — Eth_\l ether, misnamed "sulfuric ether," because sulfuric acid is used in its manufac- ture, is a colorless, very volatile and highly inflam- mable liquid, having a specific gravity of 0.726, a boiling-point of 35°, and containing not more than 4% of alcohol. With air it forms a highly exy)losive mixture: C.HjoO -(- 6O2 = 4CO, + sH.O. ether Its vapor is heavier than air, and its administration by artificial light is only permissible when the source of the latter is high above the source of the ether. Under no circumstances should ether be evaporated over an open flame. It is soluble in about ten parts of water and in all ])roportions in alcojiol and other organic solvents; it is also a good solvent, especially for all the organic acids (distinction from inorganic acids). It is employed in considerable quantities in surgery, principally because when inhaled it first produces intoxication and then anesthesia. In this respect it is similar to chloroform in that it causes insensibility. In pharmacy it is used as a solvent for resins, fats, oils, alkaloids, for the preparation of PROPERTIES OF THE ETHERS. 32 1 collodions and the 32.5% spirit (spiritus setheiis U. S. P.); this, with 2.5% of ethereal oil, constitutes Hoffmann's anodyne (spiritus aetheris compositus U. S. P.) (2) Mixed £///en.— METHYL-ETHYL ETHER, CH3— O— C2H5, is prepared by distilling methyl alcohol with ethyl sulfuric acid. It is sometimes used as an anesthetic. PROPERTIES OF THE ETHERS.— The ethers and esters of the lower members of the monatomic alcohols and of the fatty acids possess some general characteristics: they all have a pleasant odor, usually resembling that of some fruit, and mixtures of these have been used in the manufacture of synthetic fruit essences, or fruit ethers, sometimes called "fruit oils." Thus, artificial pineapple essence consists of chloroform, i part; aldehyd, i part; ethyl butyrate, 5 parts; amyl butyrate, 10 parts; with glycerin, 3 parts. Straivherry essence consists of ethyl nitrate, i part; ethyl acetate, 5 parts; ethyl formate, i part; ethyl butyrate 5 parts; methyl salicylate, i part; amyl acetate, 3 parts; amyl butyrate, 2 parts; with glycerin, 2 parts. Pear essence consists of ethyl acetate, 5 parts; amyl acetate, 10 parts; benzoic acid, i part; with glycerin, 10 parts. Apple essence is an alco- holic solution of amyl valerate. The ethers given under the first three headings above, and in the quantities given therein, should be dissolved in a sufficient quantity of pure alcohol to make 120 parts bv measure. These mixtures are very powerful and very small quantities go a long way in producing the 322 PHARMACEUTIC CHEMISTRY. flavors. When ingested in larger quantities they are deleterious. There are many other fruit essences or mixtures of ethers which are extensively employed to imitate whiskies, brandies, rums or wines, and some of them added in small quantities to young wines improve their "bouquet," which, ordinarih', is only produced in these by aging. On the other hand, the esters of the higher acids constitute the fixed oils and fats. All the esters of the monatomic alcohols and monobasic acids are neutral compounds, the lower members being volatile liquids, while the higher members are usually nonvolatile solids. The com- binations with polyatomic alcohols and polybasic acids give rise to the neutral, acid or basic com- pound esters, closely analogous to the inorganic neutral, acid or basic salts. They sometimes give rise to compounds like glycerophosphoric acid, C3H5(OH)2H2P04, which in the same molecule affords the characteristics of all these varieties of compounds. The chief difference, chemically, be- tween the ethers and the esters is in the fact that the ethers are not acted upon by alkali hydroxids, while the esters are decomposed, forming an alcohol and a salt of the alkali metal (soap). Saponification, as has been stated under Fats, is the term applied to a process resembling the action of alkali hydroxids upon the fats with the production of soap and glycerin. The same may be said that when an ester, such as ethyl acetate, is boiled with an alkali hydroxid, a salt (alkali acetate) and an alcohol (ethyl alcohol) are formed. This method is employed THE ESTERS. 323 not only for the identification of the esters, but also for the quantitative determination of their strength: CH3C OOC2H, + KOH = CH^COOK + C.H,.O H ethyl-acetic acid ester + alkali = alkali acetate + ethyl alcohol. Among the esters of the aliphatic series, ethyl acetate, methyl salicylate, ethyl nitrite, ethyl sulfate, amyl nitrite and ethyl carbamate may be mentioned. (3) Esters.— ETHYL ACETATE, acetic ether, acetic acid, ethyl-ester (aether aceticus U. S. P.), CH3COOC2H5. It is prepared by distilling a mix- ture of sodium acetate and alcohol with sulfuric acid: C2H5OH -f NaC^HjO, + H2SO, = CH3COOC2H5 + H2O + NaHSO,. The distillate is washed with a solution of calcium chlorid, to free it from the water, then with milk of lime to free it from sulfuric acid. It is next decanted dried over calcium chlorid and finally redistilled. Acetic ether is an inflammable, colorless, limpid liquid, boiling at 76°, and having a specific gravity of 0.885. It possesses a pleasant, fruity odor, not un- like that of apples, hence it has gained the name of "apple oil." It is soluble in about 8 parts of water, which becomes slightly acid from its decomposition into acetic acid and alcohol (hydrolysis) . It is soluble in alcohol and all the other organic solvents, and serves as a good solvent for the essential oils, resins, nitrocellulose and morphin. Small quantities of it added to hock wine and to eau de cologne improve their odor. ETHYL NITRITE, nitrous ether, CH^— O— NO, 324 PHARMACEUTIC CHEMISTRY. is a fragrant, ethereal mobile liquid, with a boiling- point of 16.5° and a specific gravity of 0.947. It is insoluble in water, but freely soluble in alcohol and other organic solvents. It is made by decomposing sodium nitrite with sulfuric acid in presence of ethyl alcohol, according to the following reaction: 2C2H5OH + 2NaN02 + H2SO, = 2C2H5NO,+ 2H2O + Na^SO,. This ether is official in the spirit of nitrous ether, sometimes called "sweet spirit of nitre"; spiritus aetheris dulcis (spiritus a^theris nitrosi U. S. P.). The spirit is an alcoholic solution containing about 4% of the ester; when assayed, this spirit should yield eleven times its own volume of nitric oxid (NO). The spirit is made by decomposing the sodium nitrite with the acid in presence of alcohol, as stated above, washing it with ice-water in which the pota- sium sulfate is but sparingly soluble, adding a solu- tion of sodium carbonate to neutralize the sulfuric acid, separating the ether, drying it with potas- sium carbonate and filtering it into 22 times its own weight of alcohol. The spirit is used as a diaphoretic and diuretic. It is incompatible with many common chemicals and drugs, chief of which are antipyrin, sodium salicylate, potassium iodid, fluid extract of buchu and the (annates. METHYL SALICYLATE, "artificial oil of winter- green," synthetic oil of wintergreen, CgH^ — OH — COOCH3. Methyl salicylate is a colorless liquid, ])ossessing a strong odor and taste of the oil of gaultheria, which latter is composed almost entirely ETHYL SULFATE, 325 of the above ester. It is also identical with the oil of sweet birch (betula). The liquid boils at 220°, and has a specific gravity of 1.183 to 1.185. It is slightly soluble in water, but freely soluble in alcohol and the organic solvents. It is made by heating together methyl alcohol, salicylic and sulfuric acids: CsH^.OH.COOH + CH30H + H2SO, = CeH,.OH. COO.CH3 + H2O + H2SO,. The ester is employed as a flavoring agent and as external application in rheumatism. ETHYL SULFATE, heavy oil of wine, is the true sulfuric ether, CjHj— SO,— C2H5. This is a heavy yellow oily liquid, prepared by mixing equal volumes of alcohol and sulfuric acid and, after twenty-four hours, subjecting to distillation and collecting the portion passing between 150 and 160° C. 2C,H50H + H2SO, = C2H5— SO, — C2H5 + 2H2O. When mixed with an equal volume of ether, it constitutes the official ethereal oil (oleum aethereum U. S. P.), a constituent of Hoffmann's anodyne. ETHYL CARBAMATE, urethane, ethvl urethane, /NH3 CO (aethylis carbamas U. S. P.), an ester of \OC3H, carbamic acid obtained by reacting with ethyl alcohol upon carbamid (urea) or one of its salts. It occurs in colorless, odorless prisms, melting between 50 and 51° C, and soluble in i part water, 0.6 part alcohol and the other organic solvents. Reaction : CO(NH,),HN03 +C,H,OH = NH4N03+ CONH,-0-C.H .; urea nitrate ethyl carbamate. 326 PHARMACEUTIC CHE.MISTRY. The salt is reputed as an excellent hypnotic, free from untoward after-effects. AMYL NITRITE (amylis nitris U. S. P.), C^H,!- ONO. It is a slightly yellowish liquid possessing the suffocating odor characteristic of the amyl com- pounds, a boiling-point of 96° and a specific gravity of 0.873. It is prepared by the action of nitrous acid on pentyl alcohol. The liquid is distilled and puri- fied by washing and rectification. It is insoluble in water, but miscible with all of the organic solvents. It volatilizes at ordinary temperatures, and can best he kept in hermetically sealed glass bulbs or pearls which can be crushed in a handkerchief for inhalation. It is used as a heart tonic. The liquid should be com- posed of at least 80% of amyl nitrite, chiefly the iso- amyl, 0.26 grams of which, when assayed by the official process, should yield about 40 c.c. of gas. SALACETOL, salantol, acetol salicylate, CgH^- .(OH)CO— OCH2— COCH3. It is prepared by the interaction between monochlor-acetone and sodium salicylate. The salt was introduced as a substitute for salol. It occurs in fine, needle-shaped crystals, melting at 71°; insoluble in water and cold alcohol, but freely soluble in hot alcohol and the other organic solvents. Other ethers of importance, such as ethyl and methyl benzoate, butyrate, valerate and nitrate, are all prepared by a process similar to the one given under Ethvl Acetate. CHAPTER XXVII. THE ALDEHYDS. /,0 (CnH2,0)=R— C^ H Name Formula iBoiling- I point Formaldchyd H.CHO Acetaldehyd CH3.CHO 2r Propionaldehyd C.Hs.CHO 49' Butvraldehyd C3H7.CHO 74° Isobutvraldehyd • . C3H7.CHO 63° Valeraldehyd '. i C4H9.CHO ; 102° Isovaleraldehvd C4H9.CHO 92° Caoronaldehv-d C.H„.CHO , 128° Heptaldehyd'or ((Enanthol) C6H,,.CHO 155° The examination of the above list of aldehyds and the general formula for the same will show that they are alcohols minus two hydrogen atoms. The name aldehyd was derived from dehydrogenized alcohol (a/cohol (^e/i^irogenatus) . They are obtained by the oxidation of the primary alcohols. The lowest mem- ber of the series is obtained by the oxidation of the lowest alcohol, namely, methyl alcohol. This aldehyd has sometimes been named methaldehyd, but at the present time the nomenclature of the aldehyds is obtained from the acids they form upon oxidation. Thus, the aldehyd of methyl alcohol, upon oxidation, 327 328 PHARMACEUTIC CHEMISTRY. yields formic acid, and has, therefore, been named form-aldehyd. The aldehyd of ethyl alcohol upon oxidation yields acetic acid and has accordingly been named acet-aldehyd. The aldehyd of the third alcohol yields proprionic acid and, correspondingly, has been called proprion-aldehyd. Preparation. — When the primary alcohols arc mildly oxidized, two hydrogens are removed, split- ting off water, and aldehyd is formed. By further oxidation, aldehyd takes up oxygen and becomes an acid. Aldehyds are, therefore, the intermediate products between the alcohols and acids; thus: C.H.O . C,H,() . C.H.O, alcohol aldehyd acetic acid Properties. — The characteristic property if all aldehyds is their i)ower to combine directlv with ammonia, hydrocyanic acid, the alkalin sulfites and many other substances. They are strong reducing agents. Thus, when aldehyd is added to a solution of silver nitrate, rendered alkalin with ammonia water, the solution is reduced, and metallic silver is deposited on the walls, forming a^ mirror. By oxidation aldehyds are converted into acids, and by a process of reduction they are reconverted into alco- hols. The structure of the aldehyds may be proven by the action of phosphorus pentachlorid upon them, I)roducing a dihalid derivative and splitting oft" i)hos- ])h()ric oxychlorid, as follows: C.,H,() + PC1, = C.,H,,Cl, -f VOi\ ethylidene chlorid. ALDEHVD AND KETONE GROUPS. 329 It will be seen from the above that an atom of divalent oxygen was replaced by two monovalent chlorins, indicating the presence of the characteristic radical carhonyl, a carbon atom in combination with oxygen (C = 0) and the absence of the hydroxyl ( — OH) group. These peculiar properties of the aldehyds presuppose the presence of the group /H — C{ , called the aldehvd group. ^O When ketones are treated similarly to aldehyds with phosphorus pentachlorid, a similar dihalid sub- stitution product is formed, and phosphoric oxy- chlorid is s])lit off; thus: CaH.O + PCI,-, = C3H,C1, + POCI3 acetone dichlorpropane This reaction shows that the :=C=0 group must exist in both classes of compounds and, indeed, this latter group is characteristic of all the ketones. Whereas the aldehyds are produced from primary alcohols alone, the carbonyl (CO) group must be present at the end of a carbon chain; thus: H,0 .p CH.OH + methyl alcohol H.cf + formaidehyd CH3 CH3 1 _CH30H ethyl alcohol + ^H -1 acetaldehyd 4- H2O 330 PHARMACEUTIC CFIEMISTRY. In the ketones, however, the carbonyl group must be located in the middle of a carbon chain; thus: CH3 CH3 I 1 H3C— C— O— H + O = C = + H.,0 I I H CH, secondary propyl dimethyl alcohol ketone Furthermore, it may be stated that aldehyds can be oxidized without breaking the carbon chain, whereas the ketones when subjected to oxidation lose both carbon and hydrogen in the process. This can be illustrated by the oxidation of acetaldehyd, which produces acetic acid, and of dimethyl ketone which decomposes into acetic acid, carbon dioxid and water. Aldehyds and ketones pass into alcohols on reduc- tion. Thus, acetaldehyd forms ethyl alcohol, while acetone yields secondary propyl alcohol. With hydrocyanic acid an additive compound is formed, known as cyanhydrin, of the aldehyd or ketone employed. Thus, aldehyd gives acetaldehyd cyan- hydrin, CH3CH(OH)CN, while acetone forms ace- tone cyanhydrin, CH3C(OH)(CN)CH3. With a saturated solution of sodium bisulfite, addition com- pounds known as bisulfite compounds of the re- spective aldehyd or ketone are formed; thus: /OH ^C=0 + NaHSOs = =C( \S0..,Xa When the above comijound is formed with acetal- ALDOXIMKS, KETOXIMES, ALDEHYD AMMONIAS. 33 1 dehyd, it is known as acetaldehyd sodium bisulfite, or "ethyl-oxy-sulfonate of sodium." When aldehyds and ketones are reduced with hydroxylamin by the removal of oxygen, oximes are formed. Thus, when aldehyds are treated with hydroxylamin, aldoximes are formed: CH3CHO + N H3OH = CH3CH = N0H + H,0. acetaldehyd hydroxylamin acetaldoxime With ketones a similar reaction occurs, giving rise to kdoxlmes, thus: 01^3— CO— CH3 + NH3OH = (CHQ^CNOH + acetone hydroxylamin acetoxime HjO. With hydrazin (NH2— NH2), phenylhydrazin (NH— CgHj.NHa) and some other derivatives, aldehyds and ketones combine splitting off water, forming hydrazones and phenylhydrazones ; thus: = C = O + H^N— NH— C ,H, = C = N— NH— C,H, ^Ishenylhydrazine phenylhydrazone + H,0. In the case of acetaldehyd, the product is known as acetaldehyd-phenylhydrazone, CH3— CH = N— NH— CgHj. With ammonia, aldehyds form aldehyd-ammonias; thus: .OH CH3— CHO + NH3 = CH3— CH^ aldehyd ammonia The aldehyd ammonias are soluble in water, are decomposed by acids with the formation of the 332 PHARMACEUTIC CHEMISTRY. ammonium salt of the acid and the regeneration of the aldehyds. The only aldehyd which behaves differently is formic aldehyd which gives, with am- monia, hexamethylenetetramin; thus: 6HCH() + 4NH3 = (CH^)eN, + 6H.,Q formaldehya hexamethylenetetramin The above reaction is made use of in the deter- mination of the strength of formaldehyd solutions. The caustic alkaUs have different effects upon the aldehyds from ammonia. They resinify the lower members of the series, giving rise to a brown, resinous substance of unknown composition, called aldehyd-resin. From the above comparison many points of similarity between the aldehyds and ketones can be seen. The points of difference between them are the following: (i) Aldehyds may be oxidized to monobasic acids containing the same number of carbon atoms, while the ketones (open chain), when oxidized, yield acids containing fewer carbon atoms, while the cyclic ketones form dibasic acids of the same number of carbons. (2) Aldehyds polymerize easily; ketones do not. (3) Aldehyds reduce am- moniacal solutions of silver nitrate; ketones do not. (4) Aldehyds redden solutions of magenta which have been decolorized by sulfur dioxid; ketones do not. (5) The aldehyds of the aromatic series are converted by caustic potash into a salt of tlio acid and an alcohol; ketones are not. .Aldehyds unite with the alcohols in the presence of FORMALDKHVD. ^2;^ a little hydrochloric-acid gas, forming acetals. Thus, formaldehyd combines with methyl alcohol, giving methytal, H^CXOCHj),. Acetaldehyd with ethyl alcohol yields aceial, CH3 — CH(OC2H5)2. The equation representing the reaction is as follows: CH3CH H: oaHj 0+ = CH.,-CH(0C,H 5), + H,0 H: OC,H, ethylal (ethylacetal) FORMALDEHYD, methaldehyd, formic aldehyd, "formalin," HCHO, is obtained by the oxidation of methyl alcohol by bringing its vapor mixed with air in contact with heated platinum or copper. It may also be prepared by the dry distillation of calcium formate. Formaldehyd (Hofmann, 1867) is a very pungent, acrid gas which condenses to a liquid at — 21 °. The pure formaldehyd is very unstable. Its 40% water solutions are used extensively as antisep- tics. The official solution (liquor formaldehydi U. S. P.) should contain not less than 37% by weight of absolute formaldehyd. The solution, when evapora- ted to the extent of 6 to 10 ounces to every 1000 cubic feet of room, according to Park, forms one of the most reliable disinfectants. The solution polymer- izes very rapidly, forming [)araformaldehyd, para- form. Paraform, chemically, is trioxymethylene, (C 1120)3. It is prepared by slowly evaporating a solution of formaldehyd in methyl alcohol, when colorless crystals of paraform will separate. When heated, paraform splits into three molecules of 334 PHARMACEUTIC CHEMISTRY. formaldehyd. It is a powerful agent employed for the preparation of formaldehyd, and its vapor has the advantage of not injuring the color of tapestries and fabrics of household goods. It is also used in bandaging. The gas may be conveniently generated from an ordinary alcohol lamp filled with methyl alcohol and the projecting wick surrounded with some platinum foil. The lamp is Hghted for a minute, then ex- tinguished, when the platinum will continue to glow giving off formaldehyd. Formaldehyd is a strong antiseptic, and a few drops will preserve a consider- able quantity of material. Thus, half a grain of formaldehyd will keep a quart of cow's milk sweet for several days. In technology formaldehyd has been employed for rendering gelatin and glue in- soluble in water, also as a substitute for tannin in the leather industry. Lately it has been employed in the production of artificial silk by exposing fine threads of glue to the formaldehyd vapor. With the casein (pot-cheese) of cow's milk formaldehyd forms an insoluble substance w^hich, when treated with talcum or heavy sj)ar, is made into a stone-like -material under the name of gallalith. Recently billiard-table balls and bowling-alley balls, as well as jncture frames, have been made of gallalith. When a solution of formaldehyd is mixed with lime-water, it slowly polymerizes to a sweet syrup which, upon evaporation, gives a compound having the formula (CH._.0)b. This substance is known as jormose and exhibits many properties indicating a close ALDEHYD AND PARALDEHYD. 335 relationship with grape-sugar. The above fact is very interesting, as it is supposed to have a bearing upon the production of sugar by plants. It is known that plants absorb carbon dioxid, and it is thought that during the assimilation of carbon dioxid by the green coloring matter (chlorophyl) in the presence of the sun's rays, it is converted, first, into formaldehyd which, by a process of polymerization, is converted into sugar. ALDEHYD.— This name is commonly given to acetaldehyd, ethaldehyd, CH3CHO. It is prepared by oxidation of ethyl alcohol with a solution of potas- sium dichromate in sulfuric acid: 3aH50H + KXr,0,+4H3SO= 3CH3CHO +Cr, (504)3 -fKoSO^ +7H2O. acetaldehyd It may also be produced by heating aldehyd ammonia with sulfuric acid; thus: CH3— CH + H,SO, = CH3— CHQ + NH.HSO, N^ aldehyd OH aldehyd ammonia Aldehyd is a colorless, pungent liquid, readily soluble in water and boiling at 2 1 ° C. It polymerizes readily, giving rise to paraldehyd. PARALDEHYD is a colorless liquid, boiling at 124° C. and having the formula (CH3CHO)3. It is not an aldehyd, chemically, for it does not combine with either ammonia, sodium bisulfite, nor does it 336 PHARMACEUTIC CHEMISTRY. reduce ammoniacal silver nitrate. It is prepared by adding a few drops of concentrated sulfuric acid to aldehyd. The liquid l)ecomes hot, and when cooled to 0° C. solidities, forming crystals of paraldehyd, which liquefy at 1 1 ° C. Paraldehyd (paraldehydum U. S. P.) is soluble in water, and is one of the official hypnotics. The structure is as follows: CH3 i CH HaCHCX/CH.CH., O Acetaldehyd undergoes another polymerization in presence of potassium carbonate. It condenses to hydroxybutaldehyd, commonly known as ahiol CH3CHO + CH3CHO = CH-CH (OH) — CH XUH aldol Aldol is a svru{)y litjuid, and the process is known as ''aldol condensation." TRICHLORALDEHYD, chloral, CCI3CHO. Chlo- ral is prepared by the prolonged action of chlorin upon absolute alcohol. It may be said, chemically, to be a substitution of acetaldehyd, although it can- not be obtained from it by the direct action of chlorin. The usual method of its production (Liebig, 1832), is by passing dry chlorin gas into alcohol. The reaction which takes ])lace is a com- plicated one, giving several by-products. Of these. PREPARATION AND PROPERTIES OF CHLORAL. 337 the principal one is a compound of chloral and alcohol, known as chloral-ale oholate, and having the formula CCI3— CH(OH)— OCjH^. This compound bears a relation to the acetals. Preparation. — When a slow current of chlorin is passed through cooled ethyl alcohol, the latter is converted into aldehyd: (i) CH3CH2OH + CI2 = CH3CHO + 2HCI. The liquid is next heated and the current of chlorin is continued until saturation. The chlorin acts upon the aldehyd, abstracting three-fourths of the hydrogen (united with the carbon), replacing it by chlorin, and thus producing chloral. (2) CH3CHO + 3CI2 = CCI3CHO + 3HCI. Description and Properties. — Chloral is an oih', heavy liquid with a pungent, irritating odor and a boiling-point of 98. It polymerizes like acetaldehyd on keeping or in the presence of small quantities of mineral acids. Upon addition of one-fifth of its bulk of water and shaking, the mixture solidifies with the evolution of considerable heat. The solid crystal- line substance is known as chloral hydrate (chloral hydratum U. S. P.), or hydrated chloral, having the formula : CCI3CHO + H,0 = CCl3CH(OH) 3 chloral hydrate The hydrated chloral has a very faint odor of the liquid chloral attached to it. It is largely used in medicine as a hypnotic, and it has been stated that by the sodium carbonate of the blood it is decomposed 338 PHARMACEUTIC CHEMISTRY. into chloroform, though this statement is doubted by some. Chloral hydrate is decomposed- by caustic alkalis and alkalin carbonates into chloroform and a formate of the alkali metal. It is, therefore, incompatible with the alkalis and they should never be dispensed together. 2CCI3CHO + Ca(OH),= 2CHa3 + Ca(CH0,)2 trichlor- chloroform calcium aldehyd formate CCI3CHO + KOH = CHO^ + KCHO2 trichlor- chloroform potassium aldehyd formate Similarly to aldehyd, which, with nitric acid, is oxidized to acetic acid, chloral or trichloraldehyd is oxidized by nitric acid to trichloracetic acid: (i) 2CH3CH()+ 0,= 2CH3COOH acetic acid. (2) 2CCI3CHO+ O, = 2CCI3COOH • trichloracetic acid. Trichloracetic acid (acidum trichloraceticum U. S. P.) is a monobasic, organic acid having the formula CCI3COOH. It is obtained by oxidizing chloral hydrate with nitric acid. It occurs in white, deliquescent crystals with a characteristic odor, it should be preserved in amber glass and in a cool l)lace. The acid is very soluble in all solvents, and when heated with alkali hydroxids, it decomposes into chloroform and alkali carbonate. Chloral, besides being decomposed by the alkali hydroxids and car- bonates, is also atTectcd l)y being triturated with CHLORAL-COMPOUNDS. 339 camphor, menthol, thymol, phenol and their deriva- tives, with which it Hquefies. Chloral hydrate should with water, give a clear solution free from acid and chlorin. BUTYL CHLORAL, CH3— CHCl— CCl.— CH- (OH)2, is obtained by passing chlorin into acetal- dehyd, and has properties similar to chloral. A hydrate of this body, hutyl chloral hydrate, erroneously called "croton chloral hydrate," has been used in medicine similarly to chloral. It corresponds in constitution with ordinary chloral in its being a butyl aldehyd — C3H7CHO — from a molecule of which three hydrogens have been displaced by three chlorin atoms. Bromal, CBrgCHO, is prepared like chloral, using bromin instead of chlorin. lodal similarly prepared has the formula CI3 — CHO. Besides butyl-chloral hydrate, the following com- pounds have been used as choral substitutes in medicine: CHLORALAMID (chloralformamidum U. S. P. ), a crystalline body made by direct union of formamid OH with choral, CCl3CH<^ . Melting-point, NH.CHO 115°; soluble in 20 parts water, 1.5 parts alcohol. Chloralose, anhydroglucochloral (fr. glucose and chloral), CgHn.ClgOe. Melting-point, 185°; soluble in 170 parts water, freely in alcohol. ' Hypnal, monochloral antypyrin (fr. antipyrin and chloral), a crystalline body soluble in 6 parts water. 340 PHARMACEUTIC CHEMISTRY THE KETONES. (R— CO— R) Name. Formula. Boiling- point. Acetone or dimethyl ketone CH3.CO.CH, ^6.° Propione or diethyl ketone C2H5.CO.C.H5 103- Butvrone or dipropyl ketone C3H,.CO.C,H7 144° Isobutyrone or di-isopropyl ketone C3H7CO.C3H7 : ''^■: Isovalerone or di-isobutyl ketone C4H9CO.C4H9 i 187.° Caprone or diamyl ketone C,Hx.CO.C5H„ 227." Melting point OEnanthone or dihexyl ketone. . . . C6H,3CO.C6H.3 305-° As has been said before, ketones resemble aldehyds in some respects, but they contain the group =C0. The simplest of the ketones or acetones is the ordinary dimethyl ketone, CH3 — CO — CH3, or ace- tone. ACETONE is prepared by subjecting metallic acetates to dry distillation; thus: 2NaC2H302 = Na2C03 + CH,— CO— CH3. Another synthetical reaction which also demon- strates its structure is by the action of sodium methide on carbonvl chlorid: /CI C-0-h2NaCH3 = 2NaCH-CH3-CO-CH, \ci Under Aldehyds, we stated that all primary alcohols upon o.xidation form first the corresponding aldehyds which pass intP the fatty acids containing the same number of carbon atoms; thus: CH30H^-. HCHO — HCOOH methyl alcohol formic aldehyd. formic acid. ACETONE. 341 The secondary alcohols upon oxidation form ketones; thus: CH3 CH3CH3 I \/ ■ . C = 0+H,0 CHOH 1 CH3 Acetone is prepared on a commercial scale by subjecting to dry distillation the ordinary "gray lime" obtained as a by-product in the manufacture of wood alcohol; thus: CH3 CH3-COO. I ^Ca + heat =C = 0+CaCo3 CHg^-COO^ 1 gray lime (calcium CH3 acetate) r — acetone The so-obtained acetone may be purified by adding sodium bisulfite solution and converting it into the crystalline acetone sodium bisulfite which, when filtered, pressed and distilled with sodium carbonate, gives acetone: 2(CH3)2 = C(OH)— S03Na + Na^COg = 2CH3— CO— CH3 + 2Na2S03 + CO2 + H2O. The acetone which passes over is dehydrated by calcium chlorid and redistilled. Description and Properties. — Acetone (acetonum U. S. P.) should contain not less than 99% by weight of absolute dimethyl ketone. It is a colorless liquid, with a fragrant odor similar to methyl alcohol; soluble in water, and having a boiling-point of 56° and a specific gravity of 0.792 (20°). It is soluble in water, alcohol and other organic solvents. It is 342 PHARMACEUTIC CHEMISTRY. sometimes contained in the breath of diabetic patients and in the urine — in which it may be de- tected by the iodoform reaction (Lieben's test). It is employed chiefly as a solvent for nitrocellulose, with which it forms collodions known as "acetone collodions." It is also used as a solvent in the preparation of the official oleoresins, and in the manu- facture of iodoform, chloroform, sulfonal, etc. When acetone, mixed with twice its weight of 70% sulfuric acid, is subjected to distillation, mesitylene passes over. Mesitylene is, chemically, trimethyl benzene, CgHjj, and may be said to be a conden- sation product of three molecules of acetone from which three molecules of water have been removed. KETOLS AND MERCAPTOLS.— When ketones unite with alcohols, ketoh are formed: CH3 CH, OC^H, \ c,H,oH CH3 ogH s CR^ ' ketol. dimethyl ketone When ketones unite with mercaptans, mercaptoh are formed: CH3 CH, SC3H, / C,H,SH \^/ HO \ C.H-SH CH3 sgH, CH3 ethyl mercaptol -. r -! mercaptan dimethyl ketone When mercaptols are o.xidized, they take up oxvgen much like the mercai)tans, forming com- SULFONAL AND TRIONAL. 343 pounds containing sulfonic acid. Thus, when mercaptol is treated with two molecules of oxygen, diethylsulfondimethylmethane, or sulfonal, is formed, according to the following reaction: CH3 SQH. CH3 SOXaHj ^C^ +20= "^C^ CH3 SCHs CH3 SOo^CHs mercaptol diethylsulfondimethylmethane. (sulfonal) SULFONAL is a colorless, tasteless, inodorous, crystalline body, with a melting-point of 125-126° C. and a boiling-point of 300° C. It is soluble in 15 parts of boiling water, 500 parts of cold water and in 65 parts of alcohol. It is used as a hypnotic. It is official under the title sulphonmethane (sulphon- methanum U. S. P.). When one methvl group of sulfonal is replaced CH3 SO2C2H5 by an ethyl group, y C <^ TRIONAL is formed. C2H5 SO3C0H, It is prepared by the oxidation of a mercaptol with ethylmercaptan. It is official as sulfonethylmethane (sulphonethylmethanum U. S. P.). Trional forms colorless, shining crystals, melting at 76° C, and soluble in 320 parts cold water; freely soluble in hot water, alcohol and other organic solvents. When both methyl radicals of sulfonal are replaced C^H, SO2C2H5 by ethyl radicals, / ^ \ diethylsulfon- C3H3 SO^C.Hs 344 PIIARMACKUTIC CHEMISTRY. (liethylmethane (TETRONAL) is ])roduce(i. The method of prepanition of tetronal differs from thai of sulfonal in that diethyl ketone is employed in the place of acetone. It occurs in crystalline scales, melting at 89° C, soluble in 450 parts cold water, readily in alcohol and other organic solvents. There seems to be some connection between the hypnotic action of sulfonal and the ethyl radicals it contains, for, while dimethylsulfondimethylmethane does not produce sleep, dimethylsulfondiethylmethane does. Hence the supposition that trional with three, and tetronal with four ethyl radicals should act as stronger and safer hypnotics than sulfonal, and by e.xperience, the supposition has been confirmed. HH CO O S Q O > O U ^ w o g~ •;d-3uinoq 1 O i-> ^^-______^^_^r~s-^ aq^ ^v tC .^ O^oooooo oooo wr^ 'o "> " -^vS.vS-vSw-^-^^Aw^^^ 1 1 CJ S ^ N ro r^ lO^C r^-i/iLriMi^MO ' >o' N '^^iTr r0UOi-.0CO>/-)-t-J-0-+i^ iri w^ ^ lo 5 g. odvo°r)-°ON LOMdvd2 U U U CJ U U U UCJ U U CJ U U cJ cJ U CJ :g • ^-i 1 t3 ^ >. rt S t. 1 !•- 111 o ■ It i 3 J H < hP 3 C 5 - > 1 ^ ^ -1 re c ^CJ[i c! U 'aL i_ ^ ^ 1 jutod ^^ -3ui?[3iu aqi ly II d d 3Jnss3Jd •luiu ooi JV V^VSsI 1 1 M 1 1 M M Acids CH4 — . CH4O — . CH2O — CH202= formic acid C2H6 — C.HeO— C2H4O— . C2H40,= acetic acid. C3H8 — C3H8O — CjHsO^ CjHsOj. Propionic acid. All the above acids contain but two oxygen atoms in the molecule or one COOH (carboxyl) group, and are spoken of as monobasic acids. When diatomic alcohols, are subjected to oxi- dation, acids having four oxygen atoms in the molecule or two carboxyl groups are formed, and are spoken of as dibasic acids. Similarly, we have tribasic acids and, if in addition to the carboxyl groups they contain also one or more — OH (hydroxyl) groups, they are spoken of as atomic acids; thus, tartaric acid has two hydroxyl groups and two carboxyl groups and is, therefore, spoken of as dibasic and diatomic. All organic acids contain at least one carboxyl radical or group. The car- boxyl radical is sometimes known as oxatyl, — COOH, and is monovalent. The simplest organic acid in which the carboxyl is united to hydrogen is formic acid, H — COOH, and the series of acids of which it is the first and simplest member are sometimes called formic acid or the fatty acid-series. The basisity of an organic acid depends upon 348 1'1I.\K.MA( Kl lie CIlKMISIkV. the number of carboxyl groups contained in the molecule. Thus, formic acid contains one carboxyl group and is, therefore, monobasic; oxalic acid contains two carboxyl groups and is, therefore, COOH dibasic [ ; and citric acid, containing three COOH carboxyl and one hydroxyl group, is called a tribasic, monatomic acid. Acids containing the hydroxyl group in addition to the carboxyl are also spoken of as oxy- or hydroxy acids. In this discussion no attempt will be madt to cover all the acids, but only those of pharmaceutic importance will be taken up. Properties. — The organic acids are feebler than the inorganic acids, but otherwise possess the same general properties. The higher and more complex acids are very weak in their acidic properties. A salt of an organic acid and a non-volatile metal, and upon incineration, is converted into the metallic carbonate. There are several homologous series of these organic acids, but the most important is the fatty-acid series, which derives its name from the fact thai some of its higher members are found as salts of the glyceryl radical in fats. Many of the acids of this series, are found in nature; thus formic acid, which is the first member of the series, is found in stinging nettle and red ants. The second acid of the series is acetic acid, which occurs in many plants, in certain animal secretions, and can be readily distilled from vinegar. Butvric acid, the fourth member of the series, is found FORMIC ACID. 349 in rancid butter, and valeric acid, the fifth member, is found in valerian root, etc. Occurrence. — Besides the above sources, the higher acids are found in the animal fats, in the fats of plants, and free and combined as metallic and ethereal salts. Varieties. — Above we have mentioned the simple and the hydroxy acids. Besides these we have chlor- acids which are formed when the hydrogen of an acid radical is replaced by chlorin. When the hydrogen of the acid radical is replaced by NHj, amido acids are obtained; when one of the oxygens of the carboxyl group is replaced by sulfur, thio-acids are produced. Preparation. — Several methods of preparation are known: (i) By decomposing metallic salts with sulfuric or hydrochloric acids; (2) by saponification of the esters; (3) by fermentation; (4) by destructive distillation; (5) by oxidation of the corresponding alcohols; (6) by hydrolysis of the hydrocarbon cyanids with alcoholic potash. Characteristics 0} the Series. — The fatty acids form a homologous series, of which the first nine members are colorless liquids, showing a rise of about 22° in their boiling-points for each CH2 group added; thus, butyric acid boils at 163.2°; valeric acid, 184.5°. Beginning with pelargonic acid, C9H19COOH, which is a solid, all the higher members are also solids. FORMIC ACID, H— COOH or HCHO., can be prepared by the oxidation of methyl alcohol either 350 pnARMAC?:uTic chemistry. by dropping it on spongy platinum or by distilling methyl alcohol with potassium dichromate and sulfuric acid. This latter mixture in presence of alcohol evolves oxygen with formation of potassium and chromium sulfates: CH,OH + 02=HCOOH + H20 formic acid Formic acid can also be prepared by heating glycerol, with oxalic acid to about ioo° C, when formic acid will form and distill over with the water, while another portion of it combines with the glycerol, forming glyceryl monoformate. This second portion can be recovered and a second quantity of formic acid obtained by the addition of more crystallized oxalic acid and continued heating. The glycerol takes no part in the production of the formic acid, but modifies the method of decom- position of oxalic acid: CO OH I =HCOOH + CO, CO OH formic acid oxalic acid rropoiics. — Formic acid is a clear, colorless liquid with a i)ungent, penetrating odor, boiling at ioi°C.,and having a specific gravity of 1.231 (10°). In the concentrated form it produces a blister when applied to the skin. All its salts are soluble in water, and these as well as the acid are decom- posed by strong sulfuric acid with effervescence, yielding carbon monoxid. Pure carbon monoxid mav readily l)c obtained b\' healing llic acid with ACETIC ACID. 351 Strong sulfuric acid, the latter acting as a dehydrating agent: HCOOH — H3Q = CO formic acid carbon monoxid Formic acid and its salts are strong reducing agents. On warming a few drops of it with an ammoniacal solution of silver nitrate, a silver, mirror- like deposit will form. This reaction distinguishes formic acid from all the other fatty acids, and is due \H- The above is the principal test for the acid and the formates. ACETIC ACID, CH3COOH, is official in the Phar- macopoeia in three forms: acidum aceticum, con- taining 36%; the dilute (dilutum), 6%, and the glacial (glaciate), 99%, respectively, of the absolute acid. Acetic acid may be obtained by one of two prin- cipal methods: First, by the oxidation of alcohol; second, by the dry or destructive distillation of wood. By the first method we obtain vinegar; by the second, crude acetic, or pyroligneous acid. Vinegar. — When weak alcoholic solutions, such as wine, beer or cider, are exposed to the air, the vinegar organism (mycoderma aceti), also known as "mother vinegar" or acetous ferment, starts the fermentation. Strong alcoholic liquids — i.e., those containing more than 15% of alcohol — prevent the activity of the organism. The 10% alcoholic solutions are the most favorable. The organism acts as a 352 PHARMACEUTIC CHEMISTRY. carrier or "fixer" of oxygen between the air and the alcohol. Thus, we produce, by employing beer, mali vinegar; by employing wine, wine vinegar, containing 6% and 8% of acetic acid, respectively. Wine vinegar owes its aroma to ethyl acetate and proprionate and other substances present in the wine. Quick Vinegar Process. — In this "oxidation method" a dilute alcoholic solution, not over io% strong, is permitted to slowly drop into a large cask perforated with holes for free admission of air and filled with clean wood shavings. Some warm, fermented malt liquor, such as beer, is poured upon the shavings and acts as the "mother of vinegar," or as the ferment. The alcoholic solution dripping through the cask when it comes in contact with the shavings coated with the ferment organisms, becomes oxidized, the temperature of the cask interior rises, causing a free circulation of air, and the alcoholic solution is rapidly converted into an impure solu- tion of acetic acid which issues from an orifice at the bottom of the cask. By distilling vinegar we can obtain the free acetic acid. Second Method.— As stated under the destructive distillation of wood, the aqueous solution produced therein, known as pyroligneous acid (containing acetic acid, methyl alcohol and acetone), is permitted to run into milk of lime, forming crude calcium acetate. When crude lime acetate is subjected to distillation, methyl alcohol and acetone are distilled off. The dry acetate is next distilled in cojipcr ACETIC ACID — PROPERTIES. 353 vessels with sufficient quantity of strong hydrochloric acid to decompose it: (C H3— C OQ^Ca + 2HCI = 2 CH3COOH + CaCI^ calcium acetate acetic acid The distillate contains about 50% of acetic acid, which is further purified by distillation over a little potassium dichromate. Glacial acetic acid is made by neutralizing the ordinary strong acetic acid with soda. This forms a compound crystallizing with three molecules of water and having the formula CHgCOONa + 3H2O. When fused, water of crys- tallization is expelled, and, upon addition of con- centrated sulfuric acid and distillation, the salt is decomposed and pure acetic acid passes over. The pure acid solidifies on cooling, forming a crystalline mass resembling ice, from which its name "glacial" has originated. It melts at 16.7° and boils at 119°, and has a specific gravity of 1.049. Properties, Uses and Tests. — Acetic acid is a useful solvent for organic substances because it is little affected by oxidizing agents. When it is mixed with water, contraction in volume takes place so that an aqueous solution frequently has a higher specific gravity than the pure acid, and for this reason the strength of acetic acid cannot safely be determined by hydrometer. It can be detected by its odor or by neutralizing the liquid with soda and evaporating to dryness. If sulfuric acid is now added to the residue, strong odor of vinegar develops, and, in the presence of a little alcohol, the fragrant odor of ethyl acetate will develop. With ferric chlorid, 23 354 1'HARMACF.UTIC CHEMISTRY. acetic acid and the neutral acetates will give a deep red coloration, which is destroyed on boiling, forming an insoluble basic salt. Formic acid gives similar re- actions, but it can be distinguished from acetic by its reducing power on silver nitrate solutions — a property not possessed by acetic acid. With silver nitrate, aqueous solutions of acetates give a characteristic crystalline precipitate of silver acetate which, when dried and ignited, leaves a residue equal to 64.6% of metallic silver. By this means a quantitative deter- mination of the most satisfactory kind is made and also serves as a method for identifying organic acids. Many salts of acetic acid are official, of which the most common is lead acetate, "sugar of lead," Pb(CH3COO)2,3H20. This is obtained by dissolv- ing lead carbonate in acetic acid, evaporating and crystallizing. A solution of the normal salt dissolves lead oxid (litharge) and forms basic acetate of lead (subacetate), PbjOCCHgCOO)^- This is the chief ingredient of Goulard's extract (liquor plumbi sub- acetatis U. S. P.). This solution exposed to the air turns milky through the absorption of CO. gas. All soluble compounds of lead are poisonous, and magnesium or sodium sulfates serve as reliable anti- dotes, because they form with it insoluble lead sulfate. "Iron liquor" is a solution of the acetate of iron, and "red liquor" is a solution of aluminum acetate, both used as mordants in calico dyeing and printing. The calcium salt of acetic acid is used in tlic manufacture of acetone. PROPIONIC ACID, CH.C'H.C'OOH, is m<.st BUTYRIC ACID. 355 readily obtained by oxidizing propyl alcohol with a "pyrochromic mixture." (Pyrochromic mixture is a solution of potassium dichromate in concentrated sulfuric acid, and is the most commonly used oxidiz- ing agent -of organic chemistry.) Propionic acid is found among the products of certain fermentative processes. It is soluble in water, but is thrown out of its solution when calcium chlorid is added. Otherwise, it resembles acetic acid in odor and appearance and its properties, but has a boiling- point of 141° C. It may be synthetized by hydro- lyzing ethyl cyanid (QHjCN) : C,H.— CN + 2H2O = C2H5COOH + NH3. BUTYRIC ACID, CH3— CH^— CH^— COOH, oc- curs in two isomeric modifications: Normal or fer- mentation butyric acid (Chevreul, 1814), first found in butter, in which it is present to the extent of about 7% as a glyceryl ester. It is also found in the free state in perspiration and in certain animal secretions. The principal source of it is the fermentation known as "butyric." By mixing a solution of starch with putrid cheese and chalk in presence of tartaric acid and ammonium phosphate at a temperature of about 35° C, butyric acid is formed. It may be said that the fermentation takes place in several stages; thus, the starch is first converted into glucose, this into lactic acid, and lactic acid into butyric acid: (1) CeH^.O, = 2C3He0 3 glucose lactic acid (2) 2C3H,03 = C.HsO, -f- 2CO, -h 2H, butyric acid 356 PHARMACEUTIC CHEMISTRY. Among the products of this fermentation besides the butyric acid, acetic and caproic acids may be mentioned. The free butyric acid produced com- bines with the calcium, forming calcium butyrate, which is decomposed by hydrochloric acid, and butyric acid is separated by distillation. It may also be obtained by oxidizing normal butyl alcohol. Butyric acid is an oily liquid, possessing an un- pleasant odor of perspiration and rancid butter. It is soluble in water but, like propionic acid, it is thrown out of solution by calcium chlorid. Its ester (ethyl butyrate) is employed in making arti- ficial flavoring essence of peach. Isohntyric acid has been found free or as an ester in many plants. It has the formula ^^^^CH—COOH. It is found in the oil of chamomile, or may be prepared by oxidizing isoljutyl alcohol or by the hydrolysis of isobutyronitril (isopropylcyanid). In appearance it closely resembles the normal acid, but is less soluble in water, and its calcium salt is more soluble in hot than in cold water. VALERIC ACIDS.— "Valerianic" acid has the form- ula C3H,o02 and exists in four isomeric modifications. Two of the isomerids, the isovaleric and methyl- ethyl acetic acids, are obtained by the oxidation of fusel oil. Isovaleric acid occurs as a glycerid in certain blubber oils. The above two acids are found together in the valerian group and in angelica, from which they may be obtained by distilling with water. Thev are c)il\- li((ui(ls, slightly soluble in VALERIC ACIDS. 357 water. One of these, however, the methyl-ethyl acetic acid, exists in two modifications which cannot be distinguished in appearance or by chemical properties, but which differ in certain physical [)roperties, namely, it is "optically active" — that is, it affects the plane of polarized light. All bodies possessing this property are known as "optically active" and must contain at least one asymmetric carbon atom. An asymmetric carbon atom is one in which each of the four bonds is united to a different atom or group. The following are the structural formulas of the four valeric acids, the third one of which is optically active because it contains one asymmetric carbon atom: CH3 nonnal valeric acid (propylacetic acid) CH3. >CH -CH3-COOH CJJ / isovaleric acid (isopropy- ^ lacetic acid.) CH3 CH3 I ' I C2H5-C-H CH3- C-COOH I 1 COOH CH, active valeric acid (me- trimethylacetic acid, thylethyl acetic acid) Commercially, isovaleric acid is obtained by the oxidation of the commercial amyl alcohol with pyrochromic mixture, and this is the source of the valerates employed in medicine. Valeric acid has an unpleasant, rancid odor, a boiling-point of 170° C. and a specific gravity of 0.941 (at 0° C). 358 PHARMACEUTIC CHEMISTRY. The higher homologues of the paraffinic acids occur frequently in the fats and oils and have been de- scribed under Fats. LAURIC ACID, CnHjgCOOH, occurs in the seeds of the laurel — Laurus nohilis — and in the wood of the South American Goupia tomentosa. MYRISTIC ACID, Ci^H^COOH, is found in the seeds of the wild nutmeg — Myristica moschata. MARGARIC ACID, C.^B^^COOYi, does not seem to occur in the common fats, but it can be prepared synthetically. ARACHIDIC ACID, CigHgeCOOH, occurs in the African earth nut — Arachis hypogeia. THE DIBASIC ACIDS. I ^ \C()C)HJ Melting-point Carbonic acid HO.CO.OH , Oxalic acid COOH.COOH 1 189° Ma Ionic acid COOH.CHj.COOH 134-° Succinic acid COOH.CH..CH..COOH 182.° Glutaric acid COOH.(CH,)3.COOH . 97° Adipic acid COOH.(CH,)4.COOH , 1^0.° Pimelic acid COOH.(CH,)s.COOH 103.° Preparation 0} the Dibasic Acids. — The dibasic acids are prepared by a process resembling the formation of the fatty acid series. The glycols, which name is applied to the diatomic alcohols, and which possess two primary alcohol groups, yield, on oxidation, dibasic acids. The simi)losl of the CARBONIC ACID. 359 dibasic acids and corresponding to the first glycol is oxalic acid: CHoOH CO -OH I +20,= I +2H2O CH3OH CO -OH ethylene glycol oxalic acid It will be seen from the above that two oxygen atoms have been substituted for each two hydrogen atoms of the hydrocarbons. They contain two hydrogen atoms replaceable by metals or basic radicals. They can also be formed by hydrolysis of the cyanogen derivatives of the monobasic acids. Thus, cyanacetic acid will hydrolyze with water, splitting off ammonia and giving malonic acid: /COOH /COOH CH2 +2H20 = NH3+ CH, \CN \COOH cyanacetic acid malonic acid. They can also be produced by treating dicyanids (R''(CN)2) with caustic alkalis, and by o.xidation of diatomic primary alcohols and the oxidation of hydroxyacids. Besides these methods they may be obtained by electrolysis. CARBONIC ACID, HO— COOH. While this acid has only one carboxyl group, its compounds, how- ever, are those of a dibasic acid. Its metallic salts are fully described in the inorganic part of this book. CARBONYL CHLORID, carbonoxychlorid, phos- Cl gene, COx , is obtained bv the direct union of CI 360 PHARMACEUTIC CHEMISTRY. carbon monoxid and chlorin in sunlight (Davy, 1811). Carbonyl is also formed when chloroform is oxidized in the presence of air and light. On a large scale it is produced by passing a mixture of carbon monoxid and chlorin through heated charcoal. Carbonyl chlorid condenses to a liquid at 8°, and has a suffocating, pungent smell. It has been used for the manufacture of aniline dyes and specially of crystal violet. UREA, carbamid, CO(NH2)2. This important amid is a normal constituent of urine and constitutes the chief form in which the waste nitrogen of the system is eliminated. It may be said to be derived from two molecules of ammonia in which two hydro- gen atoms were replaced by the divalent carbonyl group. Its constitutional formula is the following: C==0 . It may be prepared by evaporating urine and adding to it strong nitric acid when, on standing, yellow crystals of urea nitrate wnll be deposited. These are collected on a filter, dis- solved in boiling water and decomposed by barium carbonate, which forms barium nitrate and frees the urea. This is then evaporated to dryness on a water-bath and the dry residue is extracted with boiling alcohol, the solution is filtered and, when concentrated, deposits crystals of urea. It may also be produced from ammonium cyanate and carbonyl chlorid, both of which methods have already been described. DERRATIVES Ol' CARBONIC ACID. 361 Derivatives of Carbonic Acid. — Carbonic acid is spoken of as methane, CH^, in which two hydrogens were replaced by two hydroxyl groups and the other two hydrogens by one oxygen. Its graphic formula may be written; OH HO— C— OH; or more compactly C=0 OH. According to the above structure, sodium acid OH carbonate would be written, C=0 , the nor- 0- -Na 0- / -Na mal sodium carbonate, c^o , and ammon- \o- -Na ^0— NH, ium carbonate, C=0 \ •^ XTTT O— NH,. Allied to carbonic acid is carhamic acid; although it has never been isolated, its ammonilim salt is a constituent of the official ammonium carbonate (ammonii carbonas). Thus ammonium carbamate, 362 PHARMACEUTIC CHEMISTRY. NH4.COO.NH2, is readily obtained by passing COj into an alcoholic solution of ammonia gas: / 2NH3 + C()2 = c=o The Pharmacopoeial salt is a mixture of this and /OH the ammonium acid carbonate, C^^O ;and its \ ^ONH, formula is: NH,HC03.NH,NH,C0,. Official ammonii:m carbonate When ammonium carbamate is heated, urea is /NH, /NH, formed: CO = CO + HjO. \0— NH, \NH, Urea may, therefore, be regarded as the amid of carbonic acid; that is, carbonic acid in which both the hydroxyl groups have been replaced by amid, — NHj, groups. It is often called carta mid. Urea is found in the urine of mammals; thus, the normal daily quantity excreted by men is from 40 to 50 grams and by women 25 to 40 grams. I'rca is the end-product of the proteid metabolism in the body, and represents about 85% of total nitrogen eliminated by the body; the quantity found in urine serves as a measure of the nitrogenous metabolism in the human bodv. OXALIC ACID. 363 OXALIC ACID, H2C20„2H20, is a dibasic acid; it occurs in the form of fine crystals containing 2 mole- cules of water of crystallization. Oxalic acid may be prepared in several ways: (i) By oxidation of sugars, starches, etc., with nitric acid; (2) on the commercial scale, by heating saw-dust with caustic soda to 250° C. Sodium oxalate is produced by this method, which extracted, with lime water, is decom- posed by strong sulfuric acid into insoluble calcium sulfate, the solution containing oxalic acid is decanted, filtered, evaporated to a small bulk and crystallized. Oxalic acid is a strong poison; it occurs naturally in juices of many plants, like sorrel, rhubarb, oak, cinchona, etc. It has been used for suicidal purposes; as antidotes, magnesia (MgO), slaked lime in a httle water, or mucilaginous liquids should be given at once. If there is no vomiting, an emetic is admin- istered. Neither a stomach pump nor alkalis, or their carbonates should be used. Tests. — With calcium chlorid neutralized with ammonia water, the soluble oxalates give a crystalline precipitate soluble in hydrochloric, but insoluble in acetic acids. Properties. — Oxalic acid is one of the very strong- est organic acids, it is soluble in water;. at 100° C. it loses its water of crystallization; it sublimes at 155° C; when treated with strong sulfuric acid, it decomposes into water and the two carbon oxids: H2C2O, = H2O + CO + CO2. Oxalic acid is a strong reducing agent, it decolor- izes solutions of permanganates, and precipitates 364 PHARMACEUTIC CHEMISTRY. gold and silver. It forms two classes of salts — acid and ncrmal. Acid potassium oxalate, "salts of sorrel," binox- alate of potassium, occurs in sorrel, is used in eradi- cating iron and ink stains from fabrics, in manicuring, COOH etc.; it has the formula | COOK. Calcium oxalate is found in many plants, also as a crystalline deposit in urine; it has the formula — COO. I >Ca. COO^ COONa Sodium oxalate is | , a normal salt. COONa All ammonium, potassium and sodium oxalates are soluble; the oxalates of the other metals are practically insoluble. MALONIC ACID is a very valuable reagent in organic syntheses; it has the formula: COOH I CH2 I COOH SUCCINIC ACID.— The normal succinic acid is obtained by hydrolvzing /i-cyanpropionic acid; thus: CH^CNCH^COOH + 2H2O = COOH + NH3. /a-cyanpropionic acid I CHj I CH2 I COOH ISOSUCCINIC AND MALIC ACIUS. 365 It is prepared by dry-distilling amber, and occurs in gastric contents. ISOSUCCINIC ACID is obtained by hydrolyzing a-cyanpropionic acid: CH3 I /COOH +NH3 CH3.CHCN.COOH + 2H20=CH( ^COOH When nor null succinic acid is heated to 235° C, it yields siucinic anhydrid and water: COOH I CH2 CHj— CO. 1=1 >0 + H,0. CH^ CHj— CQ/ I succinic anhydrid COOH When this anhydrid is heated in ammonia gas = CH,.CO I /NH, succinimid is formed. CHj.CO^^ When the /^osuccinic acid is heated above 130° C, it decomposes: COOH COOH CH3 \/ CH, + CO, CH = I I COOH CH3 propionic acid In fact, any organic acid, in which two carboxyls are attached to the same carbon atom at high tem- peratures, splits off CO, from one of the carboxyls. MALIC ACID is found in unripe apples and many 366 PHARMACEUTIC CHEMISTRY. other fruits; chemically, it is hydroxy succinic acid, and COOH I has the formula | . Malic acid can be pre- CH.OH I COOH pared from the berries of mountain ash. Aspartic COOH CH2 acid is aminosuccinic acid: | , and is closely CH.NH2 I COOH related to malic acid. Malic acid crystallizes with difl&culty; it is soluble in water and alcohol; and iron malate (ferri pomatum) is mentioned in the National Formulary; it is a very efficient form of iron when used internally. Closelv related to aspartic acid is asparaqin, CO.NH2 I CH, chemicallv, amino-succin-amic acid, | ; it CH.NH2 I COOH occurs ill many leguminous plants; it is soluble in hot water, and with HNO., it is converted into malic acid. HYDROXYACIDS. 367 HYDROXYACIDS. When ethylene glycol is oxidized, qlycollic aldehyd,- CH2OH I , is formed; this further oxidized yields, CHO the corresponding hydroxyacid— glycollic acid. GLYCOLLIC ACID, CHo.OH.COOH, occurs natur- ally in the leaves of the Virginia creeper, wild vine, etc., and is prepared by treating amidoacetic acid with nitrous acid: CH.NH, CH,OH (i) 1 + HO.NO= I + H,0 + No, COOH COOH or by the action of moist silver oxid on monochlor- acetic acid: CHXl CH.OH (2)21 + Ag.,0 =2 I + 2AgCl. COOH COOH The above are two general reactions jor the prepa- ration of hydroxy acids. Glycollic acid occurs in colorless soluble needles. Chemically, it may be regarded as hydroxyacetic acid. Substitution of this kind in the paraffin derivatives leads to the possibility of isomerism, as has been stated under Valeric Acid (p. 357), and all the fatty acids beginning with propionic exhibit this possibility. Thus, in propionic acid, CH3.CH2. — COOH, the substitution may take place in the methyl (CH^) or the methylene (CH^) group, so that there are two hydroxypropionic acids possible: iS-Hydroxy propionic acid, CHjOH.CH^.COOH, 368 PHARMACEUTIC CHEMISTRY. and a-hydroxypropionic acid, CHj.CHOH.COOH = lactic acid. Nomenclature. — For the purpose of identification of the isomerids of this kind, their names are custom- arily prefixed with letters from the Greek alphabet. Thus, the position where the substitution has occurred is indicated starting with the carbon atom nearest to the carboxyl group. (To understand this, study the formulas of the above two acids.) LACTIC ACID, a-hydroxypropionic acid, oxypro- pionic acid, H.C3H5O, is a monobasic, monatomic CH3 \ acid, its graphic formula being CH.OH ; it is I COOH found in sour milk as product of hydrolysis. Thus, milk-sugar, which is normally present in milk and has the formula Q^HjjOn.HjO through the fermen- tation induced by the lactic-acid ferment (Bacillus acidi lactici), is split into lactic acid; thus: C,3H,,0„.H,0 = 4C3H,03 acid lactic Lactic acid may also be prepared by fermenting starch paste with lactic-acid ferment or by heating cane-sugar with sodium hydroxid. Lactic may be synthesized from a-aminopropionic acid by one of two general methods given under Glycollic Acid. When oxidized with potassium permanganate, it yields pyruvic acid. aCHvCH.qiLCOOH -\-0, = ,CHi.Cq.C00H+2U,0 acid lactic. pyruvic acid. LACTIC ACIDS.. 369 While the synthetic lactic acid is identical in composition and reactions with the acid obtained by fermentation, this latter acid differs in that it is "optically active." It must, therefore, contain an "asymmetric" carbon atom, and more than one form of it should be known. In reality three lactic acids are known: (i) Inactive lactic acid (ordinary). (2) Dextrolactic acid. (3) Levolactic acid. Properties.— T\\t\r chief distinction is the action on polarized light, the crystalline structure of their salts and differences in solubility. When ordinary lactic acid forms strychnine salts, compounds of both the dextro- and levo-acid are obtained and separated by crystallization. Again, when ordinary mould culture (penicilium glaucum) is introduced into solutions of ordinary lactic acid, the levo-acid is destroyed by the bacteria and the dextro-acid remains. The acid is official as a 75% solution (acidum lacticum) and its graphic formula showing the "asymmetric carbon" is the following: CH3 I H — C — OH. Sarcolactic and Paralactic acids are I COOH found in the muscle and other tissues of the body, also in meat extracts. CHAPTER XXIX. DERIVATIVES OF THE ACIES. As stated before, acetic acid, when subjected to the action of chlorin, suffers the replacement of the hydrogen atoms of the methyl group CH3, yielding three chloracetic acids: Monochlor acetic acid, CH2CI — COOH, a crystalline compound, melting at 62° C. Dichloracetic acid, CHCU— COOH, a liquid, boil- ing at igo° C. Trichloracetic acid, CCI3 — COOH, ])repared by oxidizing the aldehyd-chloral, CCI3CHO, a crystal- line compound melting at 52° C. What has been said of acetic acid holds true with all the acids of the formic-acid series; the substitution always taking place in the alkyl group and never in the carboxyl group. These halid derivatives re- tain the characteristic properties of the acids from which they are derived, since the carboxyl group remains intact. Acid Chlorids. — When phosphorus trichlorid reacts upon alcohol, it replaces the hydroxyl by a chlorin atom; thus: ^Cl C.H, »-Cl-hC,K, -OH -OH ^OH = P-OH + C,H,-C1 C3H5-CI ^Cl C2H, -OH "^OH phosphorous acid C,H,-C1 ethylchtorid 370 ACETYL CHLORID. 37 1 This reaction is characteristic of phosphorus chlorid — with all substances containing the hydroxyl groups. When, therefore, an organic acid is treated with this reagent, the hydroxyl residue of the carboxyl group is replaced by chlorin, forming an acid chlorid : 3CH3-COOH =Pa3 = 3CH,C0-C1 + H3P03 acetic acid acid chlorid (acetyl chlorid) These halid derivatives of the acids are named after the parent acid. Thus, in the above case ''acetyl chlorid" with propionic acid we obtain "propionyl chlorid," etc. The student should observe the difference in the production of monochloracetic acids and of acetyl chlorid. In producing the first class of compounds, the halogens — chlorin, bromin, etc. — replace the hydrogen of the alkyl, while in the production of acetyl chlorid the phosphorus trichlorid replaces the hydroxyl (OH) in the carboxyl (CO— OH) group bv chlorin. ACETYL CHLORID, CH3— C— CI, is a colorless, pungent liquid, fuming in contact with moist air. With water it hydrolyzes into acetic and hydrochloric acids and w-ith alkali hydroxids into corresponding acetates and chlorids. Acetyl chlorid is a valuable reagent in organic chemistry in that it reacts tvith all substances con- taining the hydroxyJ-groups, forming acetyl dcriva- 372 PHARMACEUTIC ClI F.MISTRY. lives. It acts by replacing the hydrogen of the hydroxvl groups bv the monovalent acetvl group: CH3-C(^ Alcohols, therefore, can be converted into alkyl acetates or acetic-acid esters: C.H5OH + CHj — C O — C 1 = CHs — O— CO— CH , + HC 1 alcohol acetyl chlorid ethyl acetate The saturated acids and their alkali salts when treated vi^ith acetyl chlorid have their hydrogen of the carboxyl group or the alkali metal replaced by the acetyl group, producing a new class of organic substances, namely, the acid anhydrids: CH,^-COOK + CH., - COCl = acetic acid CH3 - CO - -co - CH, + K(1 anhydrid of acetic acid (acetic anhydrid) With the higher homologues oi acetic acicl ])hospliorus chlorid reacts similarly, producing corre- s[)onding chlorids, which resemble acetyl chlorid in pr()[)erlies. ACID ANHYDRIDS.— These are produced by the interaction of acetyl chlorid and the alkali salts of the acid, as shown above. If we employ the alkali salt of a different acid, a mixed anhydrid is produced. Thus, with sodium ])ro))ionate acetyl chlorid })ro- duces acetic-i)ro|)i()nic anhydrid: CH3COCI + CH3 — CH2 — COONa = CH3— CO— ()— COCH.-CH, -f NaCl. ALKYL-SULFONIC ESTERS AND ACIDS. 373 The anhydrids bear the same relation to the acids as the ethers do to the class of alcohols: C2H5OH . ' QH— O— QH, ethyl alcohol ethyl ether ■--— (di-ethyl-oxid) (CH3— CObH . . C H3— CO — O— CO— CH 3 - acetie-acid acetic anhydrid (di-acetyl-oxid) ACETIC ANHYDRID, (CH3— CO).©, made by a process described above, is a colorless liquid with a pungent acetous odor and a boiling-point of 138° C. It combines with water slowly, forming acetic acid, and with hydroxylic compounds acetyl derivatives; thus: CH3— OH + CH3CO— O— COCH3 = CH3— O— COCH 3 + CH3COOH methylacetate ALKYL-SULFONIC ESTERS AND ACIDS.— When ethyliodid is warmed with sodium sulfite, ethyl-sul- jonic acid is formed; when ethyl mercaptan is sub- jected to direct oxidation, the same compound forms: 2C2H5— HS + 3O2 = 2C2H— HSO3 ethyl mercaptan ethyl-sulfonic acid When thionyl chlorid (SOCU) acts upon alcohol, ethyl sulfite is formed: /CI /O.C2H5 + 2HCI 2C2H5— OH + SO< =SO< _ Vl ^O.C ^H, thionyl ethyl sulfite chlorid Sulfonic acids possess acid reactions; they form salts with metals and, when treated with phosphorus trichlorid, are converted into alkvl sulfonic chlorids; 374 PHARMACEUTIC CHEMISTRY. thus ethyl-sulfonic acid yields ethyl-sulfonic chlorid, C2H5 — SO2 — CI. Tliis reaction indicates that the sulfonic acids contain a hydroxyl group. NITROGEN IN ORGANIC COMPOUNDS AND THEIR DERIVATIVES. In Chapter XX\'I the cyanogen derivatives were treated of; all the other nitrogen compounds of pharmaceutic interest will be briefly treated in this chapter. Nitrogen occurs in organic compounds as cyano- gen, as nitric or nitrous acids, ammonia, and their derivatives. Thus, nitric acid enters organic compounds by combining with organic radicals, as, for example, in nitroglycerol. Many of the organic compounds with nitric acid, are explosive. Nitro-derivatives oj the Paraffins include those compounds wherein the NOj group replaces the hydrogen of carbon compounds when these are treated with concentrated nitric acid. While the paraffin hydrocarbons can only indirectly have their hydrogen re]>!accd: CH3CI + .AgNo., = CH3.NO., + .\gCI. nitromethane Using a paraffin derivative and a salt of nitrous acid, the aromatic hydrocarbons can be treated directly with PINOg: C„H„ + HNO3 = CoHsNOj + HjO THE NITRILS. 375 The nitroderivatives, while exhibiting the prop- erties of the ethers of nitrous acid, are far more stable. NITROETHANE, C2H5.NO2, obtained similarly to nitromethane, is a colorless liciuid, with a pleasant ethereal odor, and a boiling-point of 113° C. In composition, nitroethane is identical with ethyl nitrite, but it differs in structure and properties; thus: C2H,.Q.N0 C2H5 — n:^ ethyl nitrite O nitroethane When nitroethane is treated with nascent hydrogen it is reduced to an amin: QH^.Nf -f3H2 = C2 H,.NH2 -f2H3Q O ethylamin While ethyl nitrite similarly treated, gives ethyl alcohol and ammonia: C^H^O.N:© +3H2 = C2H50H. +H3O. +NH3. When nitroethane is treated with an alkali hydroxid, sodium nitroethane is formed: //^ //^ C,H-.NC + NaOH = CH^NaNf + H,0. Ethyl nitrite, similarly treated, gives alcohol: C,H5.0.N0 + NaOH = QH^OH + Na.O.NO. THE NITRILS. In Chapter XXV methyl cyanid, CHj.C^N, was briefly treated. The importance of the nitrils is in the syntheses of the higher carbon compounds. Thus, we can pass from a one-carbon- 376 PHARMACF.UTIC CHEMISTRY. atom compound to a iu'o-carbon-a.tom compound, then to a tliree-carbon-a.toin compound, etc.: CH 3.CJI.,CE EN + 2H2O = CHaCH^.C^^ + NH3 ethyl cyanid (Jxl propionic acid It can be readily seen that propionic acid having three carbon atoms, is a derivative of propane, and yet ethyl cyanid is prepared from ethyl iodid, which has but two carbons in the molecule: CH3.CH2.I + KCN = CHg.CH^.C^N + KI. The nitrils can also be obtained by heating the corresponding ammonium salts with phosphorus pentoxid; thus: 2CH 3CQONH, + P3O5 ammonium acetate 2CH3.CN + 2H3PO, + H2O, methyl-cyanid (acetonitril) and 2C2H5COONH, + P2O5 ammonium propionate 2C,H3.CN + 2H3PO, + H3O ethylcyanid (propionitrile) It will be seen that these nitrils are named after the salts from which derived; thus, acetonitril, propionitril, etc. THE ISOCYANIDS.— This class of compounds is a.\so called car bam ins. Whereas in the nitrils the carbon of the — C=N is directly linked to the other carbon atom, in the isocyanids, it is the nitrogen of the group that is linked to the carbon; thus: :=N — CH,.N^C methyl cyanid methyl tsocyanid FULMINIC ACID. 377 Of all the metals, silver alone, instead of a cyanid, forms an wocyanid; thus: AgNO, + K— C=N = KNO3 + Ag— N=C. All the other isocvanids may be produced by heating the alkyl iodids with silver cyanid. When they are treated with water, they are decom- posed differently from the other cyanids: ,H .0 CH,— N=C + 2H,0 = CH3— N< +H.Cf methyl j'socyanid methyl amin acid formic The isocyanids are readily produced by heating together any amin with chloroform and caustic alkali: CH3NH2 + CHCI3 + 3KOH = CHjN^C + methyl amin + chloroform + alkali = methyl Mocyanid 3KCI+3HP. Properties. — All the isocyanids are poisonous and all possess a suft'ocating disagreeable odor. FULMINIC ACID.— Fulminic acid has the formula CNOH according to theory, although it has never been isolated. Mercuric fulminate \\ /Hg, C=N.O/ crystallizes with half a molecule of water = CjNgOj.- Hg + ^HgO. It is prepared by acting with alcohol on a mercuric-nitrate solution in nitric acid. When dry, the salt is a powerful explosive and detonates. It is used in percussion caps, and fired by a fuse, sharp blow or electricity. 378 PHARMACEUTIC CHEMISTRY CYANIC AND CYANURIC ACIDS.— By fusing together potassium cyanid with lead oxid, potassium cyanate, KO — C=N, and metallic lead are produced. From this, cyanic acid, HO— C=N, may be prepared. It can be crystallized from alcohol, but in aqueous solutions it decomposes into ammonia and carbon dioxid. Cyanic acid can also be prepared from cyanuric acid, C3H3N3O3, which has the graphic formula HO— C=N— C— OH 1' II N = C— N I O— H Cyanuric acid is obtained by heating urea: C3N3(OH) 3 = 3HO. CN. cyanuric acid cyanic acid When cyanuric acid is heated, cyanic acid is pro- duced: 3CO(NH,)2 = C3H3N303 + 3NH3. Cyanic acid is a strong, unstable liquid which, above 0°, polymerizes rapidly into porcelain-like, opaque mass, called cyamclide. Potassium cyanate, KO— CN, is also produced when potassium cyanid slowly oxidizes in the air. THIOCYANIC ACID, H— S— C=N, sometimes called sidjocyanic, is ol^tained in the form of its salts by heating alkali cyanids with sulfur: KCN + S = KS— CN . potassium thiocyanate Ammotiiiim thiocyanate is obtained by heating HYDROXYLAMIN. 379 carbon disulfid with ammonia in an alcoholic solu- tion : CS2 + 4NH3 = NH.CNS + (NHJ.S. Besides thiocyanic acid, we have the isothiocyanic acid, which has the formula H.N = C = S; the best known compound of this is allyl isothiocyanate, a constituent of volatile oil of mustard (oleum sinapis volatile), which should contain not less than 92% of it. SODIUM NITROPRUSSID, Na2Fe(CN)5N0.2H20, is a valuable reagent for detecting sulfids, with which it gives an intense violet color. It is prepared by acting with nitric acid on potassium ferrocyanid. It crystallizes in ruby-red prisms, soluble in water. MERCURIC THIOCYANATE, Hg(CNS)2 is obtained by adding mercuric chlorid to a solution of potassium thiocyanate. Insoluble powder separates which, on drying, takes fire on ignition, and in- tumesces with voluminous ash, aggregating in long snake-like tubes — "Pharaoh's serpents." The vapor, containing mercury, is poisonous. HYDROXYLAMIN, NH^OH, is obtained by reducing ethyl nitrate with hydrochloric acid and tin; thus: (i) 2Sn, + 8HCl = 4SnCl2 + 4H., hydrogen (2) C2H5N03-h3H2 = NH20H + C2H50H + H20. Two forms of alkvl derivatives of hvdroxvlamin are 380 PHARMACEUTIC CHEMISTRY. known: amethyl hydroxylamin, NHjOCHg, and /3 methyl hydroxylamin, CH3. NHOH. Hydroxylamin is a valuable reagent with the aldehyds and ketones, with which it forms oximes, by splitting off water; thus: CH3^HO + NH.OH =CH3X:jH = NOH +HjO acetaldehyd + hydroxylamin = acetaldoxime It will be observed that the oxime is named after the aldehyd employed; thus, from acetaldehyd we obtained acetaldoxime; likewise, oximes of the ketones are named after the parent ketone. Acetone with hydroxylamin gives: CH3.CQ .CH3 +^H,Oi^= acetone + hydroxylamin = JCHj^jCNOH + H2O acetoxime The oximes are sometimes named iso-nitroso com- pounds. NH2 HYDRAZIN, I , is a double ammonia; its NH2 compounds, especially phenyl hydra zin, CgH^NH.- NHj, also called hydrazin-benzene, i§ a valuable reagent in organic chemistry, especially in the examination of sugars, with which it forms two well- defined classes of compounds — the hydrazones and osazones. THE DERIVATIVES OF SULFUR. MERCAPTANS or suljur nhohols. Preparation. — The mercaptans are formed by PROPERTIES OF MERCAPTANS. 38 1 treating alkyl halids with potassium hydrogen sulfid; thus: CH3I +KSH = CH^SH^ KI methyl-mercaptan C^HjBr + KSH = QH^^H^ KBr. ethyl -mercaptan Properties. — Ethyl mercaptan is the most common of the class. They are mostly liquids of a dis- agreeable, garlicky odor. Similarly with alcohols, mercaptans contain a hydrogen atom replaceable by metals; thus, we have with sodium, a compound, CHgSNa; with mercury, (C2H5S)2Hg, etc. These compounds are known as mercaptids; thus, sodium methyl mercaptid, mercury ethyl mercaptid, etc. When subjected to oxidation, mercaptans differ from the alcohols in that they take up three molecules of oxygen, forming sulfonic acids: C2H5SH + 03 = QHs .SOaOH . ethyl sulfonic acid The structure of the sulfonic acids may be written — /R /CH3 SO2 ; thus, SO, is methyl sulfonic acid. \OH \6h /OH THIOCARBONIC ACID, CO — dithiocarbonic, \SH /SH also called xanthogenic acid, CO , and trithiocarhonic \SH /SH acid CS are also known \SH 382 PHARMACEUTIC CHEMISTRY. SULFUR ETHERS.— The allyl sulfid (a constit- uent of oil of garlic), (C3H5),S, mentioned elsewhere is a type of sulfur ethers. They all possess a garlicky odor and all are prepared by acting on potassium sulfid with alkyl halids. CHAPTER XXX. SUBSTITUTION PRODUCTS OF THE ACIDS. ACID AMIDS are prepared by heating ammonium salts of the corresponding monobasic organic acids in hermetically sealed tubes: CH3COONH, = CH3C O.NH3 + H.O. ammonium acetate = acetamid Each molecule of the salt loses a molecule of water. The amids are named after the acids contained in the salt; thus, from ammonium acetate acel-amid is pro- duced; from ammonium propionate, propion-amid, etc. (2) The amids may also be formed by acting with strong ammonia solution on the acid chlorids: CH3. CO.CI + NH3 = CH3.CO. NH2 + HCl. acetyl chlorid (3) Also by acting with strong ammonia on the esters: CH3.CO.OC2H5 + NH3 =CH3.CO.NH2 + C3H50H. It will be observed that the amids are organic acids in which the hydroxyl group is replaced by the amido, NH2, group: CH3.CO.OH — CH3.C O.NHa. acid amid Properties. — .Acetamid is prepared by distilling ammonium acetate in a current of dry ammonia. It 383 384 PHARMACEUTIC CHEMISTRY. is a colorless, crystalline compound, melting at 80° C, possessing the unpleasant odor of mice urine; it is soluble in water; when boiled with acids or alkalis, it hydrolyzes into acetic acid and ammonia: CH3CO.NH2 + HjO - CH3COOH + NH3. When heated with phosphorus pentoxid, acetamid is converted into methyl cyanid (acetonitrfl) : CH3.CO.NH2 — H2O = CHg.C^N. aceto-nitril AMINO ACIDS are obtained by treating organic chloracids with strong ammonia solution: CH,ClCOOH+2NH3=CH.,.NH3.COONH,+HCl. mono-chlor (glycin-ammonia) acetic acid Glycocol is the weakest acid of the amino group, and is obtained by boiling glycin-ammonia with copper carbonate, when a crystalline copper salt is obtained. This copper salt is decomposed by hydrogen sulfid. Cupric sulfid is filtered out, and the glycin is obtained by crystallization. AMINOACETIC ACID, ciNH^.COOH, it will be observed, is acetic acid, in which one- of the hydro- gens of the hydrocarbon has been replaced by the — NH2 group. It is commonly known as glycin, a crystalline substance, melting at 235 ° C. The amino- acids are of interest because they are frequently found among the decomposition products of the proteids; thus: Benzoyl glycin, "hip])uric acid," is found in llii' urine of horbivora. \Mu'n heated with strong HipPURic acid; leucin. 385 hydrochloric acid, benzoic acid and glycin are pro- duced; thus: CH,.NH[C0.C,H5 + HO]H = CH^NH^ + I ' I ' • CO.OH CQ.QH hippuric acid glycin QH^.^OOH. benzoic acid The above is the commercial method for producing benzoic acid. Methyl glycin, "sarcosin," is obtained by boiling creatin with barium hydroxid — or, synthetically, by condensing methylamin with monochloracetic acid: //CH3 H— N— CH3 N— H + CH,C1 = I \H I " CH2 + HCl. methylamin COOH | COOH sarcosin (C3H,0,) Creatin, found in meat-juice with sarcoJactic acid, is, chemically, "methyl guanidin-acetic acid," Betain, "trimethyl glycin," HO.(CH3)3N.CH2.- COOH, is found in molasses prepared from beets. Creatinin, C4H7N3O2, is the anhydrid of creatin, found in small quantities in urine. Alanin, a-aminopropionic acid, CH3.CH(NH2)- COOH, is a product of the decomposition of silk. Leucin, a-amino isobutyl acetic acid, (CH3)2.- CH.CH2.CH(NH2).COOH, a product of decom- position of glue and other albuminoid bodies, is obtained from caproic acid. 25 386 PHARMACEUTIC CHEMISTRY. AMINS are strongly basic bodies derived from ammonia, NH^, by substituting the hydrogen atoms with alkvl grouj)s; thus: . ■ /CH3 /CH3 /CH3 NH. -^ N— H — N— CH3 -- N— CH3 \ H _„\Ji XCHa amin methylamin dimethylamin trimethylamin (primary amin) (secondary amin) (tertiary amin) Thus, by substituting one hydrogen atom in ammonia, NH3, a primary amin is obtained; by substituting two hydrogens, a secondary amin, and by substituting all three hydrogens, a tertiary amin. We have, therefore, three classes of amins: the primary, containing the characteristic group — NH,; secondary, containing the group = NH, and tertiary, containing the group EEN. Preparation. — Amins may be prepared: (i) By treating alkyl halids with ammonia: CH3Br + NH3==NH3C H3Br; methyl ammonium bromid this is decomposed by distilling with alkali-hydroxid: NH3CH3Br + KOH = CH3.NH^+ KBr + H.O. methylamin Methylamin is the simplest member of the class 0/ alkaloids. (2) By reducing corresponding nitro-compounds by nascent hydrogen: CH3NO2 + 3H, = CH3.NH, + 2H,(). Dimethylamin is obtained l)y treating methyl- amin with an alkyl halid: CH3NH2 + CH3Br = (C H3)., :NH + HBr. dimethylamin PROPERTIES OF THE AMINS. 387 Trimethylamin may be obtained from dimethyl- amin by treating it with a methyl halid : (CH3)2NH + CHgBr = (CH3)3=N + HBr. trimethylamin The =NH group of the secondary amins is also called "imido" group, and secondary amins imido compounds. (3) By reducing nitrils: C,H,.CN + 2H ., = C2H ,.CH..NH2 . propionitril propylamin Properties. — Amins usually possess strong ammoni- acal odor, strong alkalin reaction, and are usually soluble in water; they precipitate metals from their solutions, and with acids they form addition products; in these last two properties they are similar to ammonia; thus: like HNOj NH3 + HCl = NH3HCI H2SO4 NH3HNO3 ' (NH3)2H2SO, HNO3 CH3NH.>+HC1 = C H3NH2HCI— — ^ methylamin m. hydrochlorid H2SO4 CH3NH.>HN03 . (CH3NH,)3H3SQ , m. nitrate m. sulfate Identification. — (i) The primary amins with ni- trous acid lose the amido group which is replaced by the hydroxyl group: CH3NH, + HNO2 = NH3.CH3.NO, intermediate com- pound which is hydrolyzed: NH3.CH3.NO2 = CH3OH. + N, + HjO. 388 PHARMACEUTIC CHEMISTRY. (The above is a method of diazotization, whereby an — OH group can be introduced in a compound.) (2) The seoeniary amins, when heated with alcoholic potash and chloroform, give the isonitril reaction (p. 377). (3) The tertiary amins combine directly with alkyl halids: (CH,)3EEN + CHJ = N(CH 3)J. tetramethyl am- monium iodid Neither of the other classes of amins afford the reactions given under each class, and these serve, therefore, as means of identification. Amins of all three classes have the property of forming double compounds with platinum chlorid analogous to the similar compounds with ammonium and potassium. This property is made use of in quantitatively identifying an amin. Thus, methyl- aminplatinumchlorid, (CH3NH,)2.PtCl6, when ig- nited, yields 41.5% of metallic platinum. COMPOUNDS ANALOGOUS TO THE AMINS. These compounds show the close chemical rela- tionships between nitrogen, phosphorus, antimony and arsenic. They are known as PHOSPHIN or phosphonium, PH^, STIBIN or stibonium, SbHg, and ARSIN or arsonium, AsHg. They may be regarded as derivatives of ordinary phosphin or arsin, etc., and, like the amins, may be primary, secondary or tertiary: PH., — 12l2<^H:. -^ I'HjCHa), — P(CH3), phosphin methyl dimethyl trimethyl phosphin phosphin phosphin ORGANO-METALLIC COMPOUNDS. 389 Quaternary phosphonium iodids and hydroxids have likewise been isolated: (CH3),P.I (CH3).P- O H tetramethyl phosphonium tetramethyl phosphonium iodid hydroxid. Preparation. — By the action of alkyl iodids on phosphin, etc.: CH3I + PH3 = PH2.CH3 + HI. From the primary, a secondary, and from this tertiary phosphin may be obtained similarly with the amins. All the phosphins are inflammable. There are no primary or secondary arsins known ; the tertiary arsins, (CH3)3As, and quaternary arsonium iodids and hydroxids are well-known: (CH3),As.I and (CH3),As.OH. CACODYL is obtained by distilling a mixture of equal parts of arsenous oxid and potassium acetate. Cacodyl was first obtained by Cadet in 1760, and is contained in "Cadet's liquid." Its composition was ascertained by Bunsen (1837), who named it cacodyl (from kakodus, stinking) in reference to its intolerable smell. It is exceedingly poisonous, inflammable and has the formula As2(CH3)4. TRIMETHYL STIBIN has the formula (CH3)3Sb, and tetramethyl stibonium hydroxid, — (CH3)^Sb.0H, both are known, but both are unimportant. ORGANO-METALLIC COMPOUNDS.— This term is applied to alkyl compounds of the metals. They resemble nonmetal-alkyl compounds, both in prop- erties and in the method of production. 390 PHARMACEUTIC CHEMISTRY. ZINC ALKYLS.— Frankland synthetised paraffins (1849) l->^' treating alkvl halids with metallic zinc: 2CH3I + Zn = C,H« + Znl,. ethane He observed, however, that an additional com- pound was formed when the zinc was in excess: /CH, CH3I + Zn =. Zn^ ^I . zinc methyl iodid. When this compound is distilled, zinc methyl is formed : /CH3 2Zn(' = Zn(CH3), + Znl, ^ I zinc methyl When halogens act on zinc methyl alkyl halids are formed: Zn(CH3)2 + 2I2 = Znl, + 2CH3I. Similarly to zinc methyl, we obtain: Hg(CH3)2 = methyl mercury; Bi(CH3)3 = methyl bismuth, and Sn(CH3), = methyl tin. etc. These compounds are very inflammable and volatile. URIC ACID AND ITS DERIVATIVES. URIC ACID, C5H4N4O3, is closely related to urea, both physiologically and chemically. It is almost the chief nitrogenous secretion in many animals,- birds and reptiles. In human urine it constitutes in quantity about one-si.\tieth that of urea secreted under normal conditions. Uric acid forms three classes of salts — neutral, acid and hyperacid urates. STRUCTURE OF URIC ACID. 39 1 Of the alkali urates only the potassium and lithium salts are soluble. Lithium urate is the most soluble, while ammonium urate is insoluble. Formation and Structure. — Uric acid, chemically, is the diureid of trioxyacryllic acid: COOH CO + II OH + CO \nh. c/ nh.X urea ' ^OH "^^^^ trioxy-acryl- lic acid NH— CO ! I _ CO C— NH\ ■ - I II >CO+H.O NH— C— NH/ uric acid It may be made artificially by heating urea with cyanacetic acid. When uric acid (or a little evaporated urine) is covered with a drop of nitric acid, evaporated to dryness, upon the addition of a drop of ammonia, a beautiful, purplish color (murexide) is developed. Xanthin and guanin produce the same reaction, but on the addition of a drop of sodium hydrcxid the red color turns to blue (distinction from xanthin, etc.). Concentrated solutions of uric acid reduce Fehling solution. PARABANIC ACID is "oxalyl urea," produced from oxalic acid, urea and phosphorus trichlorid. It /NH.CO has the formula CO | \NH.CO. 392 PHARMACEUTIC CHEMISTRY. BARBITURIC ACID is prepared hy the same re- action from malonic acid, CH^C^ ^qut^ /CO; the hydroxvl barbituric acid is CONH DIALURIC ACID, CH()H(^ ^CO; and ALLOXAN is dihydroxybarbituric acid, rOHN C(OH).,(^ ^CO. It is prepared from uric acid l^y oxidizing it with nitric acid: C5H^N,03 -f H,0+0 = C4H,N.O, + CO(NH, ), uric acid. alloxan urea XANTHIN, CjH.N.O,, is closely related to uric acid. Occurrence. — In both the vegetable and animal kingdoms, in lupine seeds, malt, tea, in meat-juices, etc. While it contains one oxygen less than uric acid on oxidation, it yields the same products — alloxan and urea. GUANIN, C5H5N5O, is obtained from guano by extracting it with hot milk of lime, then with sodium carbonate, which extracts the guanin. The product is next precipitated with acetic acid and crystallized from hot dilute hydrochloric acid. Guanin, in structure, is related to xanthin, into which it is converted with nitrous acid. When oxidized, guanin gives guanidin (CNjHg) and oxalyl urea. THEOBROMIN, CAFFEIN AND THEIN. 393 THEOBROMIN, CyHgN^Oa, has been synthetized from xanthin. Chemically, it is diwethylxanthin. Found in cacao-beans to the extent of 2%. CAFFEIN and THEIN, CgHjoN^Oj, are present in coffee and tea, after which they have been named. Cofifee beans contain 1% of caflfein, tea leaves from 1-5 to 3% of thein; these bodies are identical and usually classed among the alkaloids. Chemically, triniethylxanthins. The relationships of the forego- ing compounds may be shown by their structure: NH— CO NH— CO II II C=0 C— NH\ C=0 C NH — nh-c-nhX jIh-C-N^^'' uric acid ^^^^^^ NH— CO (CHON CO II "II C=0 C— N(CH3) — C=0 C— N(CH3) I II >H I II >H. (CH3)— N C— n/" (CH3)N C— N./ dimethyl xanthin trimethyl xanthin (theobromin) (caffein (thein) CHAPTER XXXI THE CARBOHYDRATES. Monosaccharoses Disaccharoses Polysaccharoses (C6H,,06,: (C,.H,,0„.) + Glucose, grape- + Cane-sugar, sugar, or dextrose i saccharose — Fructose, fruit- j -J- Milk-sugar, sugar, or levulose : lactose -f Galactose -f Malt-sugar, -|- Mannose maltose — Sorbinose (C6H,o05)n, + Starch -}- Cellulose — Inulin + Glycogen -|- Dextrin The gums Trisaccharose, C,8H„Ox6, -|- Raffinose, or Melitriose The term "carbohydrate," or carbhydrjte, is applied to a group of natural substances, which, in addition to carbon, contain also hydrogen and oxygen in the proportion in which these unite to form water. Cane-sugar, CjjHjjOu; glucose, CgHisOe, and starch, (CgHioOs)^, are the familiar carbohydrates. The carbohydrates are closely related; all the members of the group are alcohols, some, in addi- Note. — The algebraic signs preceding each name refer to the character of the optical rotation; thus, the minus ( — ) sign indicates levo-(left-handed) rotary, and plus (+) sign the dextro-(right-handed) rotary sugars. ,SQ4 ALDOSES AND KETOSES. 395 tion, containing aldehyd and ketone groups. Sub- stances which give reactions of two classes of sub- stances are termed "tautomeric." Carbohydrates containing the aldehyd group are termed aldoses; those containing the ketone group, ketoses. The simplest " liydroxyaldehyd,'' or aldose, is CH.(CH) glycollic aldehvd, \ ; the second, glyceric CHO CH^COH) aldehyd CII(OH), etc. Correspondingly, the lowest CHO "hydroxyketone," or ketose, is dioxyacetone, CH^COH) C=0 I CH2(0H). These are regarded as oxidation products of polyatomic alcohols. Their nomenclature consists in the termination "ose," and a Greek numeral prefix indicating the number of carbon atoms in the mole- cule. The -above-named carbohydrates may serve as examples: CH2OH CH.(OH) CH,OH I I I " — CHOH — C = CHO 1 I aldo-biose CHO CH^O-H 396 PHARMACEUTIC CHEMISTRY. The necessity for this system is apparent with the higher members which are isomeric; thus, there are four possible aldo-tetroses, eight aldo-pentoses, sixteen aldo-hexoses; besides, there are heptoses, octoses, etc., besides the isomeric ketoses. The carbohydrates are among the chief products of plant life, and to a small extent also of animal life. We have mentioned the familiar examples, as sugar, starch, etc., from the vegetable kingdom; equally important, however, are milk-sugar, glycogen and frequently grape-sugar derived from the animal organism. The extensive distribution of the carbohydrates, their extensive use as foods, as materials for the fermentation, fabric, paper and many other indus- tries, makes them very important and interesting. Classification. — Carbohydrates are naturally di- vided into those, like sugar, sweet and soluble, and into the tasteless and insoluble. The sugars are further divided into the monosaccharids, containing 6 carbons; disaccharids, with 12 carbons, and trisaccharids, with 18 carbons in the molecule. Their empiric formula is written (CeHioOj)^. For the important sugars, examine the table at the head of this article. MONOSACCHAROSES are strong reducers, sepa- rating silver from silver nitrate ammonia solution, also reducing Fehling's solution, in this respect act- ing as aldehyds. With hydrocyanic acid they form cvanhydrin , with phenylhydrazin they form hydra- zones which, upon treatment with another molecule 397 of phenylhydrazin, are converted into phenyl- hydrozone of glucozone, this, with another molecule of the reagent, gives osazone; thus: (i) CH2OH CH2OH (CH.OH), (CH.0H),+H20 CH ib+H,; N^NELC„H3= CH:N.NH.C«H5 glucose phenyl hydrazin glucose phenyl hydrazone (2) CH2OH CHOH I CHOH I CHOH I CHOH + NHj.NH.CeH, I CHrN.NH.CeH , glucose phenylhy- drazone CH.OH I CHOH I CHOH I = CHOH I C = +NH3 +NH,.C6H , I anilin CH.N.NH. CeH.; glucozone It will be seen that the second molecule of the reagent has converted the first compound into a ketone ; (3) CH.OH CHOH i CHOH I CHOH I C = O + H, N.NH.CeH, CH:N-NH.C6H, glucozone CH2OH CHOH I CHOH I CHOH I C=N.NH.C6H5+H,0 CHiN.N H.CeH ^ phenylglucosazone. (osazone) 398 PHARMACEUTIC CHEMISTRY. The osazones are nearly insoluble in water, well- defined crystals which separate from a solution con- taining the sugar. They can be readily recognized under the microscope and have a regular definite melting-point by the use of this reagent, it was pos- sible for Fischer (1887 to 1890) to identify, separate and synthetizo a number of new sugars. With hydroxylamin, the monosaccharoses give flximes, they are readily oxidized, yielding mono- and dibasic acids in the case of aldoses, while the ketoses break up into acids containing fewer carbon atoms. When warmed with nitric acid, they are all con- verted into oxalic acid, and with hydrochloric into levulinic acids. They are directly jermentable with yeast. DEXTROSE, grape-sugar or glucose, CHjOH.- (CHOH)^.CHO, occurs naturally in many fruits and sweet plants, either alone or associated with levulose. It has been named "dextrose" in that it rotates polarized light to the right, and "grape-sugar" because it is found in ripe grapes. Grape-sugar may be artificially made by hydrolyzing cane-sugar with dilute h\drochIoric acid: C..H,,0 „ -I- H^O = C6H..0 6 -f C6H..06 sugar dextrose levulose The mixture of dextrose and levulose is known as "invert sugar," and from this grape-sugar may be obtained by crystallizing from hot aUohol in whicii levulose is soluble. This inversion of the disaccharoses mav also be LEVULOSE AND GALACTOSE. 399 brought about by hydrolytic enzymes, invertase and maltase. Dextrose melts at 86° C, is soluble in water, insoluble in absolute alcohol. The specific rotation [a]D = + 52.5. LEVULOSE, jntdose, CH20H.(CHOH)3.CO.- CHjOH, occurs naturally in honey and in ripe fruits, and is produced together with grape-sugar by hydro- lyzing cane-sugar. It is best prepared from inulin by hydrolyzing it with dilute acids. It may be isolated from this by boiling with alcohol from which levulose separates in small granular crystals. It melts at 96° C, has the specific rotation [(7]D = — 93°. Levulose is soluble in water and alcohol, directly fermentable with yeast, forming alcohol and carbon dioxid; it reduces Fehling's solution. When oxid- ized, it yields trihydroxybutyric and glycollic acids, each containing fewer carbon atoms than the original sugar, thus proving that it contains the ketonic group: CH.OH C6Hi,06-f02 = CH,OH.CHO H. CHOH . COOH + | trihydroxybutric acid COOH glycollic acid. With phenylhydrazin, it produces phenylglu- cosazone, and with hydroxylamin, an oxime. GALACTOSE, CeHijOg, is produced together with dextrose by hydrolyzing milk-sugar (lactose). Ga- lactose reduces Fehling's solution, ferments with yeast, with phenylhydrazin it gives galactosazon, melting at 193° C. 400 PHARMACEUTIC CHEMISTRY. Galactose crystallizes in fine needles, melting at 163° C. DISACCHAROSES. - CANE SUGAR, sucrose, C,2H220ji, is found naturally in the sugar-cane, beet, maple and various other plants. Preparation. — By expressing the juice from the respective plants, neutralizing with lime to remove impurities and to prevent inversion by the plant- acids. The lime is removed by passing COj into the liquid, as calcium carbonate; the liquid is next evaporated in vacuo until crystallization occurs. The crude sugar is redissolved, filtered through bone-black to decolorize it, evaporated and recrystal- lized. The mother liquor, or "residual sugar- house syrup," is sold as molasses. Sugar (saccharum) is soluble in water (one-half its own weight), sparingly in alcohol. It melts at 160° C, at higher temperatures it darkens, and finally carbonizes into a dark brown syrup, known as burnt sugar or "caramel." Sucrose has the specific rotation [a] D = -H 66.5°; the rotary power of sugar is made use of in deter- mining its sucrose content. Sucrose is not directly jerwcntahle with yeast, but after inverting with dilute acids into glucose, QH,/),, -f- H2O = aCgHioOe, it ferments into alcohol and carbon dioxid. Sucrose does not reduce Fehling's solution, nor does it react with phenyihydrazin or hydroxylamin. showing that it contains neither the aldehydic nor ketonic group. LACTOSE, MALTOSE, RAFFINOSE. 401 LACTOSE, milk sugar, C12H22O11.H2O, is a natural constituent of milk. Preparation. — By removing the curd from milk by means of rennet, evaporating the "whey," filtering through bone-black and crystallizing. Lactose (saccharum lactis) is harder than sucrose and therefore valued for its attrition properties in the preparation of triturations of energetic drugs, in the making of tablets and pills. Lactose is less soluble than sucrose and maltose, it has the rotation [a] D = + 80°. Lactose reduces FehUng's solution; is not directly jermentahle with yeast; it reacts with phenylhydrazin. When boiled with dilute acids, it hydrolyzes into dextrose and galactose. When sprinkled upon strong H2SO4, it should not immediately darken (absence of sucrose). MALTOSE, malt sugar, C12H22O11.H2O, is obtained from the "wort" extracted from malt — "sprouted l)arley," and produced by the action of "diastase" upon starch. This is the object of "malting" barley; the diastase at a favorable temperature hydrolyzes the starch in the moist grain into sugar. Maltose crystallizes in small white crystals; it is very soluble in water, and has the rotation [a] D = +140° — It is directly fermentable with yeast. It reduces Fehling's solution; with phenylhydrazin it forms crystalline phenylmaltosazon. Its other reactions indicate that it is an aldehydic sugar. RAFFINOSE, Ci8H320ifi + 5H2O, is a tasteless sugar found in the sugar-beet. When boiled with 26 402 PHARMACEUTIC CHEMISTRY. dilute acids it hydrolyzes into glucose, galactose and levulose. POLYSACCHAROSES.— STARCH (amylum) is a constituent in the cells of many plants, it is usually stored in the underground stems, as potato, or in seed, as maize or wheat, etc. In Europe, starch is mainly prepared from potatoes; in America, from maize, and in India, from rice. The process of starch-making consists in grinding the tubers or seeds, washing with a stream of cold running water, which, holding the starch grains in suspension, is run off into deposit vats, where the starch deposits as a paste, which is washed and dried. The microscopic appearance of the different starches is such as to determine its source, this is a valuable property in detecting starches in powdered drugs, of which they are frequent adulterants. Starches occur in a white, amorphous ])owdcr, insoluble in water, but upon boiling the granules swell slightly, burst and partially dissolve. The soluble portion is called granulose; the insoluble, starch cellulose. Starch is colored blue with iodin. When boiled with nitric acid, dextrin (British gum) is produced. De.xtrin dissolves in water, furnishing a valuable mucilage, which may also be used for saponification purposes. When further heated, de.x- trin is finally converted into dextrose. The constitution of starch is at the present time unknown; its empiric formula is usually written (C,H,oO,0,, INULIN, (C,.H,o()5).„ is a sul)stancc replacing the GLYCOGEN AND CELLULOSE. 403 Starch granule in the cells of the compositae. It is a white powder, soluble in hot water, colored yellow with iodin, and when hydrolyzed with dilute acids it is converted wholly into levulose. GLYCOGEN, (C^U^^O^)^, is a carbhydrate occur- ring in the liver of mammals. It is a white powder, soluble in boiling water, colored brown with iodin; when boiled with dilute acids, it is hydrolyzed into dextrose, while with diastase it becomes a maltose. CELLULOSE, (Ci2H2oOio)n, is the principal con- stituent of the cell-walls of plants. While the cell walls of young plants consist almost entirely of cellulose, as these become older this is replaced by lignin and such other material as wax, gum, etc. Pure cellulose (gossypium purificatum) can be prepared from plant fibers, such as raw cotton, by washing it with ether to remove the waxes; next, with alkali carbonate to remove gum; then with hydrochloric acid to destroy the lignin, and finally with weak alkali hydroxid to neutralize the acid. In this way absorbent cotton, which is the purest form of cellulose, is produced. Pure cellulose occurs in a white amorphous mass, insoluble, but dissolved by ammoniacal copper sulfate solution, from which it may be reprecipitated in the form of a gelatinous mass by acids. By treat- ing cellulose with strong sulfuric acid, a semitrans- parent mass of "vegetable parchment" is obtained. By dipping paper into a mixture of two volumes sulfuric and one volume of water, the paper becomes 404 PHARMACEUTIC CHEMISTRY. tough and translucent. \\'ashed free from the acid and dried, it constitutes parchment paper. Strong alkali solutions produce gelatinization and thickening of the walls of vegetable fiber, followed by contraction. Advantage is taken of this fact in dipping cotton fiber and cloth, in that it produces crinkled or mercerized surfaces. Nitric acid acts upon cellulose, rapidly pro- ducing a series of cellulose nitrates known as nitrocelluloses or pyroxylins. These substances are not true nitrates, but rather nitric esters of cellulose. The hexanitrate is known as gun-cotton. NITROCELLULOSE.— The hexanitrate, C.^Yi.^O,- (O.N02)6, is the true, highly explosive gun-cotton. It is prepared by macerating pure cotton in a mixture of 3 parts fuming nitric acid and i part strong sulfuric acid for 24 hours, at a temperature not exceeding 10° C. It is next removed, washed free from the acid and carefully dried at low temperature. When compressed into cartridges it can be detonated and forms a powerful explosive. The hexanitrate is insoluble in a mixture of ether-alcohol, but forms a transparent jelly. This jelly with nitroglycerin constitutes the powerful explosive cordite. The hexanitrate dissolved in nitroglycerin con- stitutes blasting gelatin. Soluble gun-cotton, C,2Hj608(N03)4, pyroxylinum, Pyroxylin, tetranitrocellulose, consists chiefly of cellulose tetranitrate It should be kept in cartons, protected from the light. A yellowish-white, matted mass of filaments, resembling raw cotton. Exceed- EXTRACTION OF VEGETABLE DRUGS. 405 ingly inflammable, burning with a rapid, luminous flame, slowly but completely soluble in 25 parts of a mixture of alcohol (i vol.) and ether, (3 vols.), (collo- dion); also in acetone (liquid skin) and in glacial acetic acid; and precipitated from these solutions on addition of (NHJjS, gives raw, artificial silk. Gun- cotton is prepared from cellulose in which four OH groups have been replaced by four NO3 groups; thus: 2CeH,o05 + 4HNO3 = Q3H,eOe(N03), + 4^,0. This is the official or "soluble gun-cotton," while the following: 2CeH,o05 + 6HNO3 =C,,-ii,,0,{NO,), + 6H2O constitutes the hexanitrate which is the true explosive guncotton described above, and is insoluble in the mixture of alcohol and ether. From pyroxylin the collodion of the Pharmacopoeia is prepared {4%). CELLULOID, xylonite, is a substance made from pyroxylin and camphor by dissolving the former in the latter by fusion. When coloring matter is added, delightful tints are produced. This fused mass is pressed powerfully into appropriate moulds, furnishing many appurtenances of domestic and industrial utility. DEXTRIN (British gum).— Two varieties of this substance are known — the white and the yellow. It is obtained by boiling starch with water acidulated with sulfuric or nitric acids. Employed as a mucilage, which is a good emulsifying agent. EXTRACTION OF VEGETABLE DRUGS. Based on the Insolubility oj Cellulose. — A very important 4o6 PHARMACEUTIC CHEMISTRY. l)rinci])le in i)harmacy is attached to the insolubilil)- of cellulose in inorganic solvents: Cellulose forms the bulk of inert plant-matter and, being insoluble in ordinary solvents (alcohol and water), principles soluble in these solvents can readily be separated from it. Solvents used for the extraction of proximate principles (alkaloids, glucosids, resins, oleoresins, organic acids, volatile oils, fixed oils, waxes, coloring matters and various aromatic principles, etc.) are known as menstrua (sing., menstruum). PAPER (charta) is prepared directly from cellulose in the form of wood, straw or linen rags by heating in revolving cylinders with alkalis, steam and, under pressure, beating into a pulp and bleaching with chlorin gas. The pulp is transferred to endless felt-belting, revolving on heated cylinders to dry and the sheets are finally pressed between hot rollers to give them a smooth or "calendered" surface. Paper to which glue or talcum has been added to produce a gloss and high finish is called "sized." Paper to which no similar substances have been added is called "unsized" paper, and is the kind directed for the official paper. SUBERIN is a modification of cellulose and con- stitutes cork. CF CHAPTER XXXII. CYCLIC OR AROMATIC HYDROCARBONS AND THEIR DERIVATIVES. Also called carbocyclic, or closed-chain, com- pounds, and frequently BENZENE SERIES. When coal-tar is subjected to destructive distil- lation, the distillate produced upon standing separates into two layers. The upper layer is a dark brown, aqueous liquid, containing ammonia and ammonium sulfid, the lower layer consists of "coal-tar." When the coal-tar is in turn subjected to dis- tillation, two fractions are obtained — the volatile, a brown, oily liquid, and a residue of coal-tar pitch, commonly known as "asphaltum." When asphaltum is further distilled, it yields chrysene, pyrene, etc. (commercially not valuable), and a residue which is "coke." If, now, the brown, oily liquid be subjected to fractional distillation, it can be separated into two portions, one of which floats upon water and is, therefore, known as "light oils," and a second fraction possessing a higher specific gravity than water and in which it will sink, known as "heavy oils." The "light oils" contain three different classes of compounds: 407 408 PHARMACEUTIC CHEMISTRY. (i) Hydrocarbons, as benzol, toluol, three xylols, ethyl benzene, mesitylene, pseiidociimene, terpene, naphthalene dihydrid, diphenyl, methyl anthracene, also hydrocyanic and acetic acids. (2) Oxygenated substances allied to the alcohols, as phenol, ortho-, meta- and imracresols, xylenol, etc.; and, (3) Basic compounds similar to the amins, as pyridin, pyrrol, anilin, quinolin, etc. The second class, or oxygenated substances, can be removed by shaking the "light oils" with a solution of soda, with which sodium phenolates, etc., will form, while the basic compounds can be removed by treating the "oils" with dilute acids. The residue left after the second treatment is a mixture of hydrocarbons, which are the starting- point of a new homologous series of aromatic com- pounds, are separable into its constituents by frac- tional distillation, etc. Coal-tar is the chief source of benzene. It is a by-product in gas manufacture. Bitumin- ous coal yields most coal-tar, while anthracite coal yields least. The coal is subjected to destructive distillation in the process of gas making in fire-clay retorts, 6 to 8 feet long and 10 wide. Iron retorts were formerly employed for this purpose, but this metal, being readily attacked by sulfur, has been substituted by fire-clay. When coal is subjected to destructive distillation, the degree of heat employed has a great influence ILLUMINATING GAS. 409 upon the percentage and character of the fractions; thus: At 2 5 High temperature Gas, NHjH.O, Tar, Sulfur, Water, s. 20.5% 31% 17-1% 3-o% 4.2% 47-9% 45 -0% 0.3% 6.8% loo.o part Low temperature. 6.5% 7.2% 26.5% (above ioo% C, Fixed carbon, Sulfur, Ash, 40.2% 50.0% 9-0% 5. 99.2 parts. A ton of coal "furnishes the following products of destructive distillation: 11,000 cubic feet of gas and 9 gallons of tar. ILLUMINATING GAS is composed of hydrogen, marsh gas, carbon monoxid, heavy hydrocarbons, hydrosulfuric acid, ammonia, etc. When subjected to purification by being passed first through water and then through burnt lime (CaO) or iron hydrate and lime, its composition changes; thus: Before purification. After purification. H, 47% 51% CH4, 34% 36% CO, 5% 5% Heavy hydrocarbons. 4% 4% H,S, 1% none NH3, 1% none CO,, 4% none N, 4% __i% In 100 parts In 100 parts To enrich the gas or "carburette" it, higher hydrocarbons are employed, such as naphtha. 4IO PHARMACEUTIC CHEMISTRY, benzene, nai)hthalene, etc.; nai)hthalene cannot be used to advanta>fe in the winter time, as it freezes out. FRACTIONS OBTAINED BY DESTRUCTIVELY DISTILLING COAL. The fraction that passes below 80° C. is gas. The fraction that passes between 80 and 170° C. constitutes "light oils." The fraction that passes between 210 and 270° C. is composed of creasote oil, middle oil (phenol), naphthalene, and constitutes the "heavy oils." The fraction passing above 270° C. is chiefly anthracene. The "light oils" come over to the extent of 2 to 4°, when they are fractionated; "dead oil" is left behind. The "heavy oils" are found to the extent of 32 to 35%, and coke to the extent of 45%. The "heavy coal-tar oil" is not further ])unhed, but since it possesses antiseptic properties on account of the phenols it contains, it is used as a preservative for telegraph poles, for piles for bridges, for railway- sleepers and timber in general. The light oils possess an unpleasant odor, and quickly acquire a brown color by absorbing oxygen from the air; by shaking with HjSO^, however, these oxidizable bodies are charred into a tarry mass and can be removed. The separation of the constituents of the differ- ent fractions will be dcscril^ed together with the discussion of the sul)stanccs themselves. 411 BENZENE. Benzene is sometimes called benzol, phenyl-hydrid, coal-tar benzin; its chemical formula is CgHg, or CgH-H (Faraday, 1825); it has a boiling-point, of 80.5° C. Specific gravity, 0.9 at 0°, 0.87 at 25°. Preparation. — From coal-car it is obtained by the fractional distillation of the "light oils." The fraction boiling between 80° and 150° C. is employed for the preparation of benzene and its homologues. The homologues are removed by agitation with strong H2SO4. The acid removes anilin, pyridin, etc.; when it is withdrawn, the "oils" are treated with strong solution of caustic soda which unites with the phenol, forming sodium phenolate and neutralizes the residual sulfuric acid. When the soda solution is drawn off, the residual oil is washed with water and, so purified, subjected to fractional distillation in apparatus heated by steam and provided with a long fractionating column. The fraction which is first collected is known as a "50% benzene" or as a "90% benzene." These terms signify a benzene in mixture of its higher homologues as toluene and xylene. They indicate that at 100° C, 50% of the liquid will distill over in the case of the ftjty per cent, kind; and 90% in the case of the ninety per cent. kind. The fractions having higher boiling-points are known as "solvent naphtha," used as a solvent in the rubber industry, 412 PHARMACEUTIC CHEMISTRY. in water-proofing fabrics and for illuminating purposes. The "50%" and "90%" benzenes, by a second fractional distillation, are separated into benzene, toluene, xylene and thiophene (C^H^S). Synthetic Production. — (i) Benzene may be syn- thetized by treating sodium benzoate with caustic soda, just as methane is prepared from sodium acetate and caustic soda; thus: C6H5— COONa + NaOH = C6H6 + Na.COj benzene CH3— COONa + NaOH = CH4 + Na^COj methane (2) By heating benzoic acid with lime: C^HsCOOH + CaO = CeH^ + CaCOg. (3) By heating acetylene to redness in a tube of hard glass, when it polymerizes (Berthelot) : 3C2H2 = CgH^. Benzene is, therefore, a polymer of acetylene, and on this polymerization the graphic structure of benzene may be based; thus: H H I i C C III / \ H— C C— H H— C C— H III — II I H— C C— H H— C C— H J" \^ Ic = I 3 molecules of acetylene i molecule of benzene BENZENE — PROPERTIES AND CONSTITUTION. 413 When benzene is heated in a red-hot tube, it is reconverted into acetylene (not very completely). Properties. — When cooled to o° C, benzene solidifies to a solid mass which melts at 6° C. It is insoluble in HjO, but soluble in other solvents; it burns with a sooty flame, and is a good solvent for fats, resins, sulfur, iodin, etc. Its chief impurity, thiophene, is separated from it by adding concen- trated H2SO4, freezing it, and then pouring off the charred impurities from the crystalline mass. Benzene combines with 2, 4 and 6 hydrogen atoms, forming additive compounds, as benzene hexahydrid, CgHi2 (also found in Russian petroleum). With the halogens it forms different substitution compounds. The difference between these two classes of de- rivatives should be clearly distinguished: additive compounds are named similarly to the inorganic compounds; thus, benzene dichlorid, CgHgClj, cor- responds to mercury dichlorid, HgClj. Whereas substitution compounds are distinguished by at- taching the names and numerical proportions of the substituting bodies to the parent substance; thus, CgH^Clj corresponds to dichlorbenzene. Additive Compounds. Substitution Compounds. Benzene hexahydrid =C6H6H6 C6Br6 = hexabrombenzene. Benzene hexachlorid =C6H6Cl6 C6Cl6 = hexachlorbenzene. Benzene tribromid =C6H6Br3 C6H3l3 = triiodobenzene. CONSTITUTION OF BENZENE. Kekule (1866) was the first to propose the hexava- lent benzene nucleus. That is to say, three of the four carbon bonds are used up in linking with 414 PHARMACEUTIC CHEMISTRY. adjacent carbon atoms, and the fourth bond is united with hydrogen or other elements or groups of elements. Secondly, he showed that the six hydrogen atoms are eqiii-valent; that is, when either one is substituted by another atom, one, and only one, derivative can be obtained. And in reality there are no isomeric mono- substitution compounds of benzene. Thirdly, that only three disuhstitution compounds can exist, and in reality only three have ever been prepared. This has been equally true when both the substitut- ing groups are the same, as in dimethylbenzene, and when both the groups are different, as in methyl- amido benzene. Fourthly, that with three similar substituting groups only three isomeric trisuhstitution derivatives are possible, and in reality only three trisubstitution products of benzene are known. In opposition to Kekule's theory, some chemists hold: First, that unsaturated compounds of the fatty series in which the olefinic linking (double-bond) is assumed, such as ethylene, allyl alcohol, etc., pos- sess the property of forming with bromin addition compounds at the ordinary temperature without splitting off hydrogen and forming hydrobromic acid, which fact is in contradistinction to the parafEnic linking (single bond) in which the hydrogen is split off with the formation of substitution compounds. Thus, if Kekule's assumption were correct, six bromin atoms -would unite directly with benzene under ordinary conditions, which, however, occurs THE BKNZENE RING. 415 only in direct sunlight, therefore not without the aid of active force. Secondly, there must be possible, according to Kekule's theory, two orthodisubstitu- tion derivatives; one of them where the adjacent two carbon atoms are linked by a double bond: + ' + + II Others suggested benzene nuclei in which the alter- nate single and double bonds are done away with, and nine single bonds introduced instead, as the one shown in the Armstrong ring: I I :i> O ON 00 r^ a 6 " Tj- ro ro i-O ^O \0 r^vo LO^O u-> m rS) " H M M 1-1 M M i d-dd, add 1 ^_Qxi •9-9-° 'o 6 £ d iga SI ~ f^o 00 00 2 o d tc o~"^^o^ oT" ^^ ££ ^i^^ o ^ "S O M vO in '^ '^ 00_ ro ^§8 ^§S§§ £■ ^ d d d d o d d 1 g' a u ^ o ^ ffi ^ S rt Z U If ^ A § ilisi 1 -" OJ o g >, -^ l! ^ o ^X ffi E 66 U U ^ OOOOO O OO ' O O lo •^ -1- lO M « ** Tl- 'I t^Os o O r- u^ro ^o ^ . M M N M PI be - _ _ - - - _ „ ~ - .S cidd d.d. d. dd dd 'o pxfxi £ - - £ xi B~ m >. > iS M g~^ (_, o -< >NH.. benzidine Of the important benzidine dyes, the following mav I)e mentioned: CHRYSAMIN, made by acting with sodium salicvlate upon diphenyltetrazochlorid: DIAZO-AMIDO COMPOUNDS. 447 \C00Na /OH /OH CeH^N.Cl + C6H4/ C6H4.N,.C6H3/ \COONa OH + 2HCI. OH C6H4N3CI+C6H / C6H4.N2.C6H3< \COONa \COONa chrysamine ;03Na^ CONGO-RED = (CeH,.N2.C,oH,/ -^^^3^^) 'NH, N = N r T-T I I \/ /\ I I BIEBRICH SCARLET ►3I i I The benzidine dyes can be used in dye'ng cotton \ ithout a mordant. THE DIAZO-AMIDO COMPOUNDS. This series of compounds is formed by adding an amido to a diazo compound. These compounds, upon standing, are transformed into AZO-AMIDO COMPOUNDS. DIAZOAMIDOBENZENE is obtained as follows: CeH.N.Cl + NH.CeH, = C6H,N,.NH.C6H, + HCl. diazobenzene anilin diazoamidobenzene chlorid 29 448 I'llARiMACEUTlC CHEMISTRY. This compound occurs in golden-yellow prisms which, when heated with anilin, yield: AMIDOAZOBENZENE, C«H,.N,,.NH.C«H, -^ C«H3.N,.C„H,.NH,. Structures oj the two: H /\ I /\ /\ /\ -N=N- -N = N-N- I I I I 1 r I I \/ 1 I I I -NHj diazoamidobenzene amidoazobenzene THE HYDROXYAZO-BENZENES are formed from phenol and a diazo compound. Like the amido- azo benzene, they form valuable dyes, of which those derived from para-amidosulfonic acid — are mostly valued, in that they dye silks and wool without a mordant. Structure: -N = N— I I I I OH. The rchitiouship oj the iiiiro compounds is best ;hown by the following structural formulas: ^0 (2) M — N = N— NO3 N:H, diazobenzene nitrate phenyl hvdrazin HYDROXY BENZENES. (3) H -N = N— N— 449 diazoamidobenzene (4) amidoazobenzene (5) _N = N— -NH, -O— H h ydroxyazoben z en e HYDROXY BENZENES. There are three classes of hydroxy benzenes: those containing one hydroxyl —OH group known as phenols, those containing two hydroxyh, known as diatomic or dihydroxyphenols, and with three hydroxyls, the triatomic phenols. The monatomic phenols have no isomers, but the diatomic phenols each have three isomers. There are two kinds of hydroxyderivatives of 450 PHARMACEUTIC CHEMISTRY. the aromatic hydrocarbons: those in which the hydroxy! group is substituted for the hydrogen of the nucleus and those in which the substitution takes place in the side chain. The first kind are known as phenols, the last as aromatic alcohols. Preparation. — (i) By fusion of sulfonic acids with potassium hydroxid: C^Hs.SOg.K + KOH= CeHs — OH + KjSOg. potassium benzol phenol sulfonate (2) By prolonged boiling of diazobenzene chlorid with water: CfiHs.N^ — CI + H.O = C,H,.OH + N^ + HCl. diazobenzene phenol chlorid Properties. — The phenols contain the tertiary alcohol group =C — OH, and therefore appear to be allied to the tertiary alcohols; and in reality they are acted upon similarly by the oxidizing agents. Like alcohols, the phenols form ethers and esters; and, as stated above, they may be monacid (CgH^-OH), diacid (C6H^(OH)2), or triacid (C8H3(OH)3). Phenols and the aromatic alcohols are isomeric, I)ut possess entirely different properties. PHENOL, C,H^OU, phenol, phenic acid, phen>l alcohol, phenyl hydrate (acidum carbolicum U. S. P. '90). Chemically, it is not an acid-, but a phenol or hydroxy benzene, hence the change in pharmaco- ])(x;ial name. Purity, 96%. Phenol resembles crea- sote in its odor and caustic ])ro])erties, but differs in chemical composition in being a solid at ordinary temperatures. Melting-point, 40°. It is soluble PHENOL AND PREPARATIONS. 45 1 in 9.6 parts water (creasote in 140 parts water). Boiling-point, 100° C. Insoluble in benzin, and coagulates collodion when mixed with it. Phenol liquejactum, liquefied phenol. Strength, 86.4% of phenol, 13.6% of water. Prepared by melting phenol in an unstoppered bottle on a water- bath and mixing it with 10% of its weight of distilled water. By using alcohol instead of water, corking the bottle and placing "upside down," solution may be effected without heat. Dose, i gr., largely diluted. It is a caustic and deadly poison. Alcohol prevents its caustic effect, and should be first admin- istered, followed by large doses of magnesium sulfate in solution, which forms a harmless sulfocarbolate of magnesium. Preparations: Unguentum phen- olis (3%); glyceritum (liquefied phenol, 20 %). Used as a disinfectant and antiseptic dressing. Car- bolic lotion is prepared by dissolving one part of the acid in 30 parts hot water (carbolized water). Note. — Observe that the solution of phenol is of 5% strength, while liquefied phenol is 86.4%. Tests. — With ferric chlorid, dilute solutions of phenol are colored violet. With bromin water a precipitate of tribromphenol is produced. This is known as hromal, CgHjBrgOH, upon the formation of which the phenol assay method depends. PHENOL ETHERS.— There are many valuable ethers and esters of phenol, many of which replace the natural odors of the flowers. PHENYLMETHYL ETHER, CgHj.O.CHg, is called 452 IMfARMACEUTIC CHEMISTRY. anisol. It can be obaincd from anisic acid (methoxy- benzoic acid) by boiling with barium hydroxid, or by synthesis from potassium phenolate with an alkvl halid: C«H, — OK + CHJ = CfiH5^aCH3^+ KI potassium anisol phenolate ETHYLPHENYL ETHER, or phenetol, is CoH^- — O — QHj, and can be produced ))y the above method, using an ethyl halid. DIPHENYL ETHER, CgHs.O.CeH^, resembles the ethyl ether. Among the esters we may mention: PHENYL ACETATE, CyH5O.CO.CH3, can be obtained by treating i)henol with acetyl chlorid. OTHER DERIVATIVES OF PHENOL. THE PHENOL SULFONIC ACIDS.— W hen phenol is dissolved in concentrated sulfuric acid, upon warming, a mixture of ortho- and para-sulionic acids is formed. These are colorless, deliquescent, crystal- line bodies, which, when fused with potassium hydroxid, yield corresponding diatomic phenols. Phenolsulfonic acids are variously known as sitljo- carbolic or sozolic acids, also as aseptol, and have /C0H5OH. the formula SO, \()IT Preparation. — By dissolving phenol in strong sulfuric acid: C„H,.OH + H,SO, = C.,H,.0H.HS0 3 + H.,0. phenolsulfonic acid. Used as an antiseptic wash in 109^. acjueous solu- tions. THE NITRO-PHENOLS. 453 SODIUM PHENOLSULFONATE, sodii phenol- sulfonas (sulfocarbolas, '90 j, sodium sulfocarbolate, NaSOg— CeH^.OH, is prepared by acting with phenosulfonic acid on sodium carljonate; a white, crystalline, soluble salt. SODIUM ICHTHYO-SULFONIC ACID, ichthyol, also ammonium ichthyo sidjonate, obtained by destructive distillation of bituminous shale found in Tyrolean Mountains. Undoubtedly obtained from fossilized aquatic animals by dry distillation. A dark oily distillate is obtained which, treated with an excess of sulfuric acid, yields ichthyolsulfonic acid. This latter product is purified and neutralized with ammonia or sodium hydroxid, yielding, corres- pondingly, the ammonium or sodium salt. The substance contains about 10% of sulfur. It is soluble in water, glycerin and the oils, also in a mixture of alcohol and ether. Used in skin and rheumatic affections, also in lung affections, exhibited in keratin-coated capsules. Formula^ C28H3gS30g. NO2 THE NITRO PHENOLS, CJ:l^(^ . When dilute nitric acid acts upon phenol, ortho- and para- mononitro phenols are yielded. These are separated by steam distillation, the or tho nit ro phenol being volatilized. ORTHO-NITROPHENOL is slightly soluble in water, readily in the organic solvents. It occurs in canary-yellow crystals, melting at 45 ° C. PARA-NITROPHENOL occurs in colorless needles, 454 IMIARMACEUTIC CHEMISTRY. melting at 114° C; also soluble in water to a small extent. (OH) TRINITROPHENOL C ,U^(^ (i, 2, 4, 6), (N02)3 picric or carbazotic acid, is formed very easily when strong nitric acid acts upon phenol. This is best done in the presence of sulfuric acid. This acid also results from the action of strong nitric acid on various substances such as wool, silk, resin, and indeed, the yellow stains upon the hands produced by strong nitric acid are due to picric acid. Picric acid occurs in brilliant yellow crystals, melting at 123° C; soluble in hot water, and rede- positing as the solution cools. It explodes under per- cussion and is extensively used for this purpose under the name lyddite. Ammonium picrate, C6H2(N02)3.- O.NH^; is also used in explosives. Picric acid possesses acidic properties and readily forms salts. It is a good yellow dye for wool and silk, but the color is affected by light. It will not dye cotton, and thereby forms a reliable test for its detection in mixed goods. PHENYL MERCAPTAN, CeH^.SH, phenyl hydro- siilfid, thiophenol, bears the same relation to phenol that mercaptan does to alcohol. It can be pre- pared bv reducing benzcnc-sulfonic acid. /CH, THE CRESOLS, C„H,(^ , or methyl phenols. OH cresvlic acids, hvdroxv toluols. There are three CREASOTE. 455 isomeric cresols, all found in pine- and coal-tars; they are similar to phenol. To obtain pure cresols, it is best to prepare these from the three toluidins. CRESOL, C7H7OH (Duclos, 1859), formerly known as cresylic acid, a mixture of three isomeric cresols is obtained from coal-tar and separated from phenol by fractional distillation. It is a refractive liquid of a strong, phenol-like odor, colorless, but becoming brown on exposure, soluble in 60 parts water and all other solvents. Used as disinfectant and deodorant. One to 5% solutions are more certain antiseptics than phenol minus its poisonous properties. Creolin, lysol, are preparations similar to Liquor cresolis compositus, a 5o'>(, solution of cresol in soft soap. CH, CH, CH, OH OH orthocresol melting- point 3 1° C. metacresoi melt- ing-point 4° C. OH paracresol melt- ing-point 36° C. CREASOTE is a mixture of phenols, cresols and guaiacol, obtained from wood (fagus silvatica), tar. There is also coal-tar creasote in commerce, which consists largely of phenol. CREASOTUM.— A mixture of several substances belonging to the class known as phenols. It is ob- tained by distilling wood-tar, preferably that from 456 PHARMACEUTIC CHEMISTRY. beechwood. Boiling-point above 200° C. ; consisting chiefly of guaiacol (C^HgO,) and cresol (C^HjoOz). The distillate from tar separates into two layers; the heavier one is freed from impurities by treatment alternately with KOH and HjSO^, and the portion boiling between 200° and 220° C. is separated by fractional distillation. An almost colorless, oily liquid, of a penetrating, smoky odor and a burning, caustic taste, darkening on age; gelatinizes but does not solidify at the freezing-point (difference from phenol). It is intlammable, burning with a smoky flame. It coagulates the albumin of the skin, pro- ducing a white stain. It is neutral. Specifac gravity, 1.07. Soluble in 140 parts water (phenol in 19.6 parts water). It is soluble in benzin and does not coagulate collodion (difference from phenol). It is also soluble in alcohol, ether, chloro- form, fixed and volatile oils. Used to deaden pain and preserve tissue, as an application in toothache; internally to allay nausea; in consumption and lung diseases. Preparation: Aqua creasoti (a saturated solution). GUAIACOL, CyHgOs- Guaiacol, the chief con- stituent of creasote (85%), is obtained by purification and fractional distillation. Synthetically, by methy- lization of catechol. A colorless, refractive liquid, of an agreeable, aromatic odor; specific gravity, 1.14; or a crystalline solid melting at 28.5 C. Soluble in 53 parts water, in alcohol and ether in all propor- tions, and in i part glycerin. Used as substitute for creasote in tuberculosis, in eli.xirs, .syrui:)s oils, C.UAIACOL CARBONATE AND THYMOL. 457 emulsions and in capsules. Chemically, it is mono- , , .. TT /O — CH3 methyl pyrocatechol, C-eH^ < GUAIACOL CARBONATE, guaiacolis carbonas, (C7H70)X03. Obtained by the action of carbonyl chlorid on sodium guaiacolate. An almost tasteless, odorless, white, crystalline powder, insoluble in water; soluble in 48 parts alcohol; in 1.5 parts chloroform; slightly in ether. Used as guaiacol ip tuberculosis in powder form. Chemically, it is di-monomethyl (CpH-.CHg.Ox^^ ^ CH CH 0/ ') Among the higher monatomic phenols, we have thymol and carvacrol. CH3 (1) THYMOL,— CgHg— OH (2), propylmetacresol, ^C3H, (4) is a phenol occurring together with cymene in the oil of thyme. It can be synthetically prepared from nitrocuminic aldehyd, CgHg — CHO — NOj — C3H7 (1,3, 4). Thymol forms large monoclinic crys- tals, melting at 50°, its odor reminds one of thyme, it is one of the two possible hydroxy derivatives of cymene, the other being carvacrol, which has also been obtained from the oil of carawav: CH, CH, OH OH C3H, C3H, thymol, melting- carvacrol, boiling- point, 50° point, 236° 458 PHARMACEUTIC CHEMISTRY. AMIDOPHENOLS, C,H. OH are produced xNH, by reducing the corresponding nitrophenols with hydrogen. They occur as colorless crystalline substances, basic in character. Meta-amido phenol forms the basis of some of the rhodamin dyes. Para-amido phenol is a solid, melting at 184°, and yielding an ethyl ether paraphenetidin, CgH^^f 2& ■\ this is converted by glacial acetic acid into an acetyl derivative phenacetin. PHENACETIN (acetphenelidinum), CeH^.NH.Q- HgO. (QH^O) . A phenol derivative made by acetaliz- ing para-amidophenetol. Chemically, para-acetic- phenetidin. White, crystalline scales or powder, odorless, tasteless. Soluble in 925 parts water, 12 parts alcohol, also ether and chloroform. Used as analgesic and antipyretic in powders or capsules. It melts at 134° C, should not give precipitate with bromin water (acetanilid). Preparation. — From para-nitrophenol, by convert- ing it into nitrophenylethyl ether, this reduced w-ith hvdrogen to form para-amidophenol, this acetylated bv boiling with glacial acetic acid; thus: OH O.QH., O.QH5 O.C2H5 NO, NO. para-nitio- phenol para-nitro- phenol ethyl ether _NH2 para-amido- phenetol NHCHgO para-acetamino- phenetol (acet. phenetidin) LACTOPHENIN, HOLOCAIN, PHENOCOLL. 459 If, instead of acetic acid, lactic acid be employed in the last reaction: LACTOPHENIN, C.H.(NH^C.H,0„isproduced. Both are used as antipyretics. Two other derivatives of para-aniido — phenol are: O.C3H, HOLOCAIN, CfiH / and ^0,H, PHENOCOLL, C,h/2h.CO.CH,NH, = ^^^^°- acetic acid derivative. CHAPTER XXXV. DIATOMIC PHENOLS. There are three isomeric diatomic (diacid) phenols. They are produced by fusing together the disulfonic acids with potassium hydroxid. They occur in horses' urine (pyrocatechin), and in human urine (hydroquinon) after administration of phenol; resorcinol is obtained by melting galbanum, asafetida and other resins: OH OH OH OH I I I 1 OH OH ortho-dihyd/oxy- benzene catechol (pyrocatechin) melting-point, 104° C. meta - dihydroxy- benzene resorcinol (resorcin) melting- point, 119° C. para-dihydroxy- benzene quinol (hydroquinone) melting-point, 169° C. CATECHOL, pyrocatechin, C«H,(OH).,, (1.2), occurs in nature in cutch, from which it derived its name, in kino, and obtained by the fusion of many gums with the alkalis. It is a colorless crystalline solid, soluble in water and in other solvents. Its solutions in alkali hydro.xids absorb oxvgen from the air and ra])idly l)CComc brown. Willi ferric chloric! its solutions are colored green — 460 RESORCINOL, FLUORESCEIN, EOSIN. 46 1 this being characteristic of all the urtho-dihyclroxy phenols. When catechol is treattd with methyl iodic! , mono- methyl ether of catechol, guaiacoJ, CgH^(^ OCH ^^ produced. RESORCINOL (resorcinum), C^Yi^^OU),^, (1.3), resorcin, a diatomic phenol (metadih3'droxy benzene). Obtained by action of alkalis on metabenzene disulfonates. Faintly reddish crystals; very soluble in alcohol and water. Melting-point, 110° to iii°C. Used as antiseptic, antiseborrheic in solutions, ointments, etc. Incompatible with ferric chlorid (violet color); with hypochlorite solutions (violet to yellow), with spirit of nitrous ether (dark red); on trituration, it liquefies or softens with phenol, menthol, camphor, chloral hydrate, acetanilid, anti- pyrin, etc. With phthalic anhydrid, when heated, resorcin forms a brown substance, which is soluble in caustic alkalis. The alkali solution of the body added to water produces brilliant green fluorescence, and hence the name of — FLUORESCEIN, QoHi^O^, resorcin-phthalein, has /CeH3(0H), the structure C— C6H3(OH), , and is mostly used in ^CeH,C = I O the making of — EOSIN or tetrabromfluorescein pink dyes. When fluorescein is acted upon by bromin in acetic acid 462 PHARMACEUTIC CHEMISTRY. solution, eosins are produced. The ordinary eosin dve is the sodium salt of tetrabromfluorescein: /C„HBr,ONa. C«H / O CeHBr^ONa. c=o PHENOLPHTHALEIN is obtained by heating one molecule of phthalic anhydrid with two molecules of phenol to 115° C. With the addition of strong sulfuric acid, phenolphthalein is formed. It occurs as a white, crystalline substance, melting at 251°; slightly soluble in water, but soluble in alcohol. It constitutes a valuable indicator in volumetric analysis, turning pink with alkalis. Slrurture, /CgH^OH C— C„H,OH. C«H,.CO phenol phthalein. RHODAMINES constitute some of the best brilliant red dyes. They are obtained from meta-amido- phenol and ])hthalic anhvdrid. Structure, '^/'CJI,.NH, ^ c I ^C„H3.NH, AURIN, ROSOLIC ACID, INDIGO. 463 AURIN is prepared by heating together phenol and oxalic acid in presence of strong sulfuric acid. ROSOLIC ACID is prepared from a mixture of phenol, cresol and arsenic acid in presence of a dehydrating agent. Both the above dyes are struc- turally represented — C^C,H,OH aurin CeH3(CH3)OH INDIGO, one of the most valuable blue dyes, is obtained from the leaves of the indigo plant (indigo- fera tinctoria), indigenous to India. Commercial indigo is not the pure substance, but a mixture of varying quantities of other coloring matters, as indigo brown, indiruhin, etc. It can be purified by crystallizing it from anilin, and as such it is known as indigotin or ^^ pure indigo.''^ Indigo synthesis has taken up the chemist's atten- tion for many years. It is now prepared synthetic- ally by one of two following methods: (i) From ortho-nitrobenzaldehyd and acetone with dilute sodium hydroxid solution: CHO 4- 2C = o I "^CH, CteHtoN^O^ + 2CH3COOH + 2H3O. 30 464 PHARMACEUTIC CHEMISTRY. (2) From anthranilic and chloracetic acid forming phenyl-glycine o-carboxylic acid; the process consists of two steps: (a) /COOH /C(OH)\ CeH/ =C6H4< )CH + CO.+ H,0. Xnh.c h. cqoh \ NH / Phenyl-glycine o-carboxylic indoxyl. acid (b) /C(OH)v 2C6H/ )CH + O. = \ NH / C6H4/ >C = C< >C6H4-t-2H.O. Xnh/ \nh/ indigo. MALACHITE GREEN, benzaldehyd green, is made by heating together benzaldehyd, dimethyl anilin and zinc chlorid. This forms the water-insoluble, colorless leuco-hase, H— C^CeH,.N(CH,), \C6H ,i\(CIT.,)3 leuco-base this, oxidized with lead peroxid and HCl, gives Cl.cf-CeH.N.CCH^)^ ^C,H. N.(CH3)3 malachite green. ROSANILIN, also called fuchsin and niat^cnta, was originally oinaincd by heating anilin and ])ara- toluidin with arsenic. It was one of the first dyes produced. The product is magenta arsenate, which, on addi- ANILIX AND METHYLP:NE BLUES. 465 tion of sodium chlorid, is converted into the hydro- chlorid. Structure, C(CeH,.NH2)2 C HC^>iCH HCll llCH NH.HCl para-rosanilm- hydrochlorid. ANILIN BLUE is obtained from rosanilin by heating it with anilin and acetic acid. Each of the three amino groups loses one hydrogen atom which is replaced by a phenyl-group: C ^—C H N/^H triphenyl rosanilin hydrochlorid (anilin blue). METHYLTHIONIN HYDROCHLORID is- /C.H,/N(CH,), N ? \ ^ methylene-biue. 466 PHARMACEUTIC CHEMISTRY. CRYSTAL VIOLET is the hexamethyl derivative of para-rosanilin. It has the structure /CH3 -CeH,.N CgH^.N CH3 .CH3 CH3 /CH3 I VH3 \ crystal violet. METHYL VIOLET has the structure • /C,H,N(CH3)3 Cf CeH,N(CH3)3 I \C6H,NCH3HC1 pyoktanin The above dyes, with the exception of indigo, may be said to be derivatives of tri phenyl methane, H.C^CeH,. Many other important dyes are known, Init of less interest to the pharmaceutic student than the above types. OH CREOSOL, methyl dioxytoluene, OCH3 CH, occurs m creasote. QUINOL AND ORCINOL. 467 QUINOL, CyHj(OH).,, hydroquinon, hydroquinon is usually made by reducing quinon or by fusing paraiodophenol with potassium hydroxid. It oc- curs in leaflets or prisms melting at 169° C; soluble in water. Its alkalin solutions absorb oxygen from the air. It is used for the above reason in photography as a reducing agent. By oxidizing hydroquinon quinon is produced, C 611^02; with two molecules of hydroxylamin it forms quinon- dioxime, O N— OH /\ II II _^ O N— OH ORCINOL, dihydroxytoluene, C6H3CH3(OH)2, can be conveniently classed with the dihydroxyphenols. Orcinol is obtained from several varieties of lichens, artificially by melting chlortoluene sulfonic acid with potassium hydroxid. It occurs in colorless prisms which turn red on exposure, and with ferric chlorid, deep blue. Orcinol treated with ammonia is converted into orcein, CjgHj^NjOy, which with alkalis gives a red dye. This is the chief use of orcin. Orcin is closely related to archil, litmus and cud- bear, three dye-stuffs, all prepared from the lichens by macerating them with urine which, when decom- posed, yields ammonia, and this develops the coloring principles. 468 PHARMACEUTIC CHEMISTRY. DYEING. Having mentioned the important dyes, a discussion of dyeing should prove interesting and instructive. It has been stated that a large part of the economic value of coal-tar products consists in the dyes made therefrom. Thus, the important "Turkey-red" from madder, "indigo" from the indigo plant of India and "log- wood black" from logwood, have all been replaced by the corresponding alizarin from anthracene, indigo from naphthalene and nigrosin from anilin. Likewise the number of plant dyes are limited while the artificial dyes are almost numberless and constantly increasing in number. DYES are frequently classified in two ways: (a) Into substantive dyes, which color fabrics with- out a mordant, and objective dyes, which color fabrics with mordants only. (b) Into basic dyes, usually a hydrochlorid of an aromatic amid, and acid dyes, the sodium salts of a sulfonic aromatic acid. MORDANTS (from Latin mordere, to bite in), a:e substances like albumin, which combine with dyes, making double compounds; and with the basic dyes, acids, like tannic, or salts, like stannic chlorid and tartar emetic, precipitate in the fiber of the fabric insoluble lakes. Mordants, therefore, are sub- stances which fix colors on fabrics. THE FIBERS USED can be divided into animal or vegetable. The animal fibers embrace wool, the hair of sheep; DYEING. 469 hair of goats and camel, etc.; silk, the libers from which the cocoons of the silk-worm are spun; feathers of the various fowl, etc. The vegetable fibers embrace cotton, chiefly pure cellulose; jute, the hemp fiber; linen, the flax fiber; straw, esparto, etc. PREPARATION OF THE FIBERS.— The fibers are generally washed to remove coloring material, grease, wax and dirt. This is frequently done by boiling with lime or soda-ash. These alkalis should, however, be used in moderation, excess weakens the fiber. The fibers, washed free from the alkali, are next bleached. This is effected by the use of solutions of bleaching powder, Ca(Cl20) or sodium hypochlorite, NaClO. Potassium permanganate solutions fol- lowed by thiosulfates are also used. Wool contains about 50% of its weight of a fatty suint, or residue from evaporated perspiration, which must be freed by boiling it with alkalis. Wool and silk can be bleached with sulfur dioxid. Bleaching is necessary in almost every case to prevent the impairment of the color produced in the subsequent dyeing. Dyeing consists in macerating the skeins of threads or pieces of the finished fabric in an acid or alkalin bath containing the dye. Almost all the colors have affinity for wool and silk, and no mordants are necessary. Not so with cotton; so few dyes affect cotton that invariably mordants must be employed. A dye must of necessity be a colored substance, but 470 I'lIARMACF.UTK CHEMISTRY. not all colored substances are necessarily dyes, unless they can i\x themselves to the fabric in such a way that washing or rubbing cannot remove them. Thus, azobenzcne is highly colored, but it will not dye fabrics. Likewise wdien silk or wool are placed in a solution of picric acid, they will be dyed a beautiful yellow; calico or other cotton material will also be colored yellow; but upon w-ashing, the dye, while permanent in silk and wool, will wash out from the cotton fabric. Therefore, some sub- stances may be dyes for a given material, but not for other materials. This property is common to many dyes. Again, materials may be steeped in basic dyes, like rosanilin, which is colorless by itself; but if the material has previously been steeped in a mordant, precipitation of a colloidal dye with the mordant will be affected in the fiber, producing lasting fast (not washed out or bleached) colors. Indigo, on the other hand, is converted into leuco'indigotin by reducing agents, which render it soluble in water. The yarn or material saturated with this solution and wrung out, iTpon exposure, while drying will become dyed; the solution is con- verted to the insoluble blue-indlgotin deposited in fibers of the fabric. Various decoctions of tanning materials, such as nutgalls, oak-bark or sumach, upon the addition of some salt of iron, produce desirable "ink-blacks" which are "fast." TRIATOMIC PHENOLS. 47 1 TRIATOMIC PHENOLS. There are three triatomic (triacid) i)hcnt)ls; all isomeric CbH3(OH)3 compounds: Of these three isomers pyrogallol is the most important, oxyhydroquinon the least. OH OH OH OH OH OH ' OH OH vicinal trihydroxy- symmetic trihydroxy- OH benzene benzene phloro- -—. — — ^r: pyrogallol glucinol ^ "dro^^'-b^nzene^" oxyhydroquinone. PYROGALLOL, C6H3(OH)3 (Scheele, 1786), also called pyrogaUic acid, like all phenols, has acid properties. It is obtained by heating gallic acid: =z(ov[\ /'OH(i) C'R—^^^^f, = C«H3-OH(2) + CO,. 2\C00H \0H(3) gallic acid pyrogallol. Pyrogallol occurs in colorless needles, and melts at 132° C. It sublimes readily and is more soluble in water than in alcohol and ether. Pyrogallol readily absorbs oxygen, and for that purpose is employed in gas analysis. It is a prompt reducing agent, em- ployed in photography and as external antiseptic in medicine. Pyrogallol is very poisonous. PHLOROGLUCINOL, C6H3(OH)3, phloroglucin, is found in certain resins as "dragon's blood" and gamboge. It can be prepared by fusing resorcinol 472 PHARMACEUTIC CHEMISTRY. with potash, whereby resorcinol takes up another - oxygen atom from the air: /OH(i) CeH,(OH), + O = C„H.— OH(3) \0H(5) resorcinol phloroglucinol. When dissolved in strong hydrochloric acid, it acquires a pink color in the presence of pentoses, for which it is a reagent. It melts at 218° C, sublimes readily and is very soluble. OXYHYDRCQUINON is oljtaincd by fusing quinol with caustic soda. AROMATIC ALCOHOLS, ALDEHYDS AND KETONES. The aromatic alcohols possess many properties in common with the paraffinic alcohols. They may likewise be produced by reactions analogous to those discussed under the Preparation of the Aliphatic Alcohols: (i) By acting with moist silver oxid on a halid of a benzene homologue. (2) By reducing an aromatic aldehyd or a ketone. (3) By acting on amino derivatives of the aro- matic hydrocarbons having the amino group in the alkyl (side chain). The two following are tyi)ical aromatic alcoliols: BENZYL ALCOHOL, CeHj.CHjOM, may be prepared by any of the above reactions or by boiling benzyl chlorid with a solution of potassium carbonate : 2C«H, CH,C1 + K2CO3 + H^O = 2CeHs .C H,0H + benzyl chlorid benzyl alcohol 2KCI + CO2 PHENOL ALCOHOLS. 473 Properties. — This is the simplest aromatic alcohol ; it occurs naturally in the balsams of tolu and Peru ; boiling-point, 206°. It forms derivatives and substi- tution products like the aliphatic primary alcohols; thus, an aldehyd — the benzyl aldehyd — and an acid — the benzoic acid: CH,OH CHO COOH benzaldehyd boiling-point, 179° C. benzoic acid melt- ing-point, 122° C. benzyl alcohol boiling-point, 206° C. CINNAMYL ALCOHOL, styrone, CeHsCHiCH.- CH20H(C9HeOH). It occurs naturally in styrax; it is a crystalline body, melting-point, 32° C, having a delightful hyacinth-like odor. It is obtained by reducing cinnamic aldehyd with sodium amalgam. There is another class of aromatic alcohols and aldehyds distinguished, namely, those in which the hydroxy! group is present, both in the side chain and the nucleus; or the OH in the nucleus and CH2OH group in the side chain. These are some- times called — PHENOL ALCOHOLS.— Example, ortho-hydroxy- henzyl alcohol, or SALICYL ALCOHOL, saligenin, /OH CeH, XCH^— OH. Salicyl alcohol occurs as a glucosid in certam 474 PHARMACEUTIC CHEMISTRY. willow barks under the name sal kin. Salicin acted upon by the enzym emulsin yields saUgenin. It may be also prepared by reducing salicylic aldehyd. It is a water-soluble, crystalline substance, melting at 82° C. ANISYL ALCOHOL, para-methoxy-benzyl-alcohol, CeH,(OCH3)CH20H, can be obtained from anisic aldehyd by treatment with alcoholic potash. Color- less crystals melting at 25° and boiling at 259°; upon oxidation, converted into anisic aldehyd, and this into anisic acid. VANIL-ALCOHOL, vanillin alcohol CgHg.OH.- OCH3.CH2OH, is formed from vanillin. Crystals melting at 115° C. PIPERONYL ALCOHOL, heliotropol, is formed from piperonal similarly to vanil-alcohol by reducing solutions of the respective aldehyds with sodium- amalgam. Crystals melting at 57° C. AROMATIC ALDEHYDS.— These, like the alco- hols, are divided into those containing the CHO (aldehydic) group, either in the side chain or in the nucleus. They are analogous to the aliphatic alde- hyds. Upon oxidation, they yield Aromatic acids just like their aliphatic analogues. The general methods of preparation of the aromatic aldehyds is by: (i) Oxidation of the corresponding alcohol with nitric acid or potassium dichromate. (2) By distilling a mixture of the corresponding acid calcium salt with calcium formate. BENZALDEHYD, CeHj— CHO (benzaldehydum), is artificially produced "oil of bitter almc^nds." BENZALDEHYD-PREPARATION. 475 It may also be obtained from natural oil of bitter almonds, peach- or cherry-kernel oil, etc. The U. S. P. requires at least 85% of benzaldehyd, and a boiling-point of 180°, specific gravity, 1.045, and be free from hydrocyanic acid and chlorinated products. (i) Benzaldehyd may be obtained by macerating ground bitter almonds when, through the decom- position of aniygdalin in the presence of water, benzaldehyd and hydrocyanic acid are formed: C.oH.7NOrT + (2)H,0 = C6H,.CHO + HCN + :C6Hi,06 amygaalii, benzaldehyd dextrose. (2) By the interaction and distillation of calcium benzoate and formate: Ca(C6H5.COO). + Ca(H.COO). = 2C6H,.CHO + 2CaC03 calc. benzoate calc. formate benzaldehyd. (3) Commercially, it is made by treating toluene with chlorin, which forms henzal chlorid, CgHj.- CHCI2; this heated under pressure with slaked lime gives benzaldehyd: (a) C6H,.CH3 + 2Cb = CeH .CHC l. + 2HCI. toluene benzal chlorid (ft) C6H5CHCI3 + Ca(OH)=CaCb +C6H5CHO + H,0. benzaldehyd. Description. — A colorless oil with a strong odor of bitter almonds, but free from hydrocyanic acid, upon oxidation yielding benzoic acid, which is sometimes seen as a deposit in the bottles containing old bitter almond oil. It is not poisonous when pure, but its freedom from hydrocyanic acid should be 476 PHARMACEUTIC CHEMISTRY established. With nitric acid it is converted into ortho- and metn-niti-obenzaldehyds. CI-I3 CH2OH CHO COOH CHO toluene boil- benzylalcohol benzaldehyd benzoic acid o. nitroben- ing-point, boiling-point, boiling-point, melting- zaldehyd, iii°C. 2o6°C. i8o°C. point, i2i°C. melting- point, 46° C. To the class of phenol aldehyds or oxyaldehyds the following belong: SALICYLIC ALDEHYD, saUcylal, orchidee, oil of spirea (meadow-sweet), CgH^.OH.CHO, can be obtained by oxidizing salicin with potassium dichro- mate in presence of sulfuric acid; synthetically, it is made by heating phenol, chloroform and caustic potash. Salicylic aldehyd has an adhesive strong odor, reminding one of sweet clover, in the manufac- ture of the extract of which it enters; it has the specific gravity of 1.17, and boils at 196° C. Reaction, known as "Reimer's synthesis": CeHj.OH -f CHCI3 + 3KOH = ^«"^\CHO + ^^^^ + '"^^ CINNAMIC ALDEHYD, "synthetic oil of cinna- mon" or "cassia" (cinnaldehydum), CgH^.CH = CH.CHO. It can be obtained from the oils of cinnamon or cassia in which it occurs naturally, or it can be prepared synthetically by condensing benzaldehyd with acetaldehyd, evaporating thejun- 'Tombined acetaldehyd and distilling w^ith steam VANILLIN. 47 7 It can also — as can most aromatic aldehyds— be obtained by forming a bisulfitic compound with the oil of cassia. It occurs as a pale, yellowish liquid, having a strong cinnamon-like odor and taste, boiling at 250° C. and having a specific gravity of 1.047. It should be at least 95% pure and free from chlorinated bodies. ANISIC ALDEHYD, CfiH,/"^^^'^^^ , anisal, "hawthorn oil," aubepine, can be synthetically obtained by oxidizing fennel or anise oil with nitric acid. Chemically, it is para- methoxy benzaldehyd, a fragrant oil, boiling at 246° C, and having a specific gravity of 1.126 (15°); at a low temperature, solidi- fying. Upon exposure it is oxidized to anisic acid. With cumarin and orris tincture, in alcoholic solu- tions, it constitutes the "new-mown hay" extract. PROTOCHATECHUIC ALDEHYD, C6H3(OH)2- CHO. It may be prepared from pyrocatechin with chloroform and caustic potash (Reimer's reaction). It melts at 150° and is chiefly of interest because of its close relation to vanillin and heliotropin. VANILLIN, tnethylprotocatechuic aldehyd, /OCH3 (i) CeH3^0H (2), \CHO (4) occurs naturally in vanilla to which it imparts its delicious odor and flavor. It can be prepared synthetically by "Reimer's synthesis" from mono- methvl ether of catechol (CeH^^ „ _„ guaiacol). \ULxlo 478 PHARMACEUTIC CHEMISTRY. Of late it has been prepared by oxidizing eugenol (constituent of clove oil) with ozone. Vanillin is a delightfully fragrant substance, with an odor of vanilla, melting at 80° C. and boiling at 285° C. When 2.5 % of vanillin is mixed with 97.5% of sugar, "vanillin sugar " is produced which can be used, weight for weight, in place of the best vanilla bean. CUMINIC ALDEHYD, CgHnCHO, is a constituent in the volatile oils of the iimbellijercB (cummin, caraway and water hemlock). CHO(i) PIPERONAL, CfiH^C^^CH,, methylene ether oj 0(4) protacatechuic aldehyd, hciiotropin, may be ()l)tained ])y oxidizing piperic acid. Small fragrant crystals, with a flowery odor of bitter almonds, melting at 37° C. Recently it has been prepared by oxidizing isosafrol with pyrochromic mixture diluted with water. Heliotropin possesses a delightful clinging odor of the white heliotrope flower, and mixed with alcohol its 2% solution with cumarin and oil of jasmin forms a fragrant "heliotrope extract." AROMATIC KETONES are analogous with the fattv ketones; their general formula is R — CO — R' — one of the two R rei)rcsenting an aromatic radicle. ACETOPHENONE is a typical aromatic ketone. Chemicall}-, it is phciiyhiicthylkclone or acetyl benzene, CgH. — CO — CH,. It is produced by THE QUINONES. 479 distilling a mixture of calcium benzoate and calcium acetate: Ca(C6H5.COO)3 + Ca(CH3COO), = 2C6Hs.CO.CH, + CaCO, acetophenone Acetophenone crystallizes in large transparent plates, melting at 21° C, and boiling at 200° C, and possessing an odor like benzaldehyd. It is known in pharmacy as hypnone, and in medicine employed as a soporific. BENZOPHENONE, CeHs.CO.CeH^, diphenyl ketone, is produced by the dry distillation of calcium benzoate: CaCQHs.COO), = CeH^ CO-QHs + CaCOg. diphenyi ketone. It occurs in colorless prisms, melting at 49° C; on reduction with sodium amalgam, it produces a corresponding secondary alcohol, CgHj.CHOH.- ^6^5 = di phenyl alcohol. THE QUINONES may be described as aromatic diketones. Benzoquinon, the representative of the class commonly known as quinon, is usually ob- tained hy the oxidation of para-derivatives, such as para- amidophenol or hydroquinol: O OH II + + H,0 OH hydroquinol 480 PHARMACEUTIC CHEMISTRY. TABLE OF AROMATIC ACIDS AND HYDROXY ACIDS. Monobasic Si:lurated Acids. Melting- point Benzoic acid, C^Hg-COOH 121° Phenylacetic acid. C6H5.CH,.COOH 76° I 0-, 102° Toluic acids, CeH,(CH3).COOH -^ m-, 110° ( P-, 180° Hydrocinnamic acid, C6H5.CH2.CH2.COOH . 4.9° Mesitylenic acid ) c^H3(CH3),COOH. . . . \ l^ Xylylic acids j » sv 3/2 / ^ o Cumic acid, C6H,(C3H7)COOH ^ 116-= Polyhasic Saturated Acids. COOH ) i 0-, 213° Phthalic acids, CeH,/ -....- m-, 300° + ^COOH \ I p- Trimesic acid, C8H3(COOH)3 300° Pyromellitic acid, C6H2(COOH), ^64° Benzene-penta-carboxylic acid, CgH (COOH). .... Mellitic acid, ^(COOH)^ .' .... Unsaturated Acids. Cinnamic acid, CeH5CH = CH.COOH 133° Atropic acid, CbHg.C^^p^^TT 106° Phenyl-propiolic acid, C6H5.C = C. COOH . . 136° Phenol Acids and AlcoJiol Acids. Salicylic acid, C6H,(OH)COOH 155° m- and p- oxybenzoic acids, CbH^(OH)- COOH ( m-, 200^ ( P-, 210° AROMATIC ACIDS. 481 Anisic acid, C„H,(OCH3)COOH 184° Oxytolulic acids, CbH3(CH3)^ rOOH i Melilotic acid, CoH,(OH)CHXHXOOH. . . 128° Mandelic acid, CeH^.CHOH.COOH 118° Tropic acid. C,Vi^Cll(^^f^^ } 117° Protocatechuic acid, CeH3(OH)2COOH 199° Vanillic acid, CeH3(OH)(OCH3).COOH.. . . 207° Orsellinic acid, QH^fCHg) (OI-I),COOH. ... 176° Gallic acid, C6H2(OH)3.COOI-I.'' 222° Tannic acid, Cj^H^pOg Quinic acid, C,H.Hg(OH),COOH 162° Unsaturated Phenol Acid. Coumaric acid, C6H,(0H)CTI = CH.- COOH ( 0-, 208° I P-, 206° AROMATIC ACIDS. These acids are also known as carboxylic, andean be produced by methods analogous to those em- ployed in the production of the aliphatic acids. These acids are divisible into three classes: Those containing the carboxyl group in the side chain, as cinnamic acid, CgHg.CH = CH.COOH; those con- taining the carboxyl group on the nucleus, as benzoic acid, CeHg.OH, and those which besides the carboxyl group contain also a hydroxyl group. This third class of acids is known as "phenol- or alcohol- acids''; example, salicylic acid, CyHj.OH.COOH. 482 rHARMACEUTIC CHEMISTRY. CH=CH.COOH COOH COOH '\ /\ /\ OH cinnamic acid benzoic acid salicylic acid (hydroxy-benzoic) General Properties.— AW the aromatic acids are crystalline; all sparingly soluble in water, but freely in the organic solvents. They can be distilled with- out decomposition, but when distilled with lime they are decomposed, losing carbon dioxid and forming a corresponding hydrocarbon: C.Hs.COOH + CaO = ^CeHe.. + CaCOg. benzoic acid benzene. BENZOIC ACID, CfiH.COOH, was so named because it was first obtained from the balsamic resin — benzoin. Like all the organic acids, it can be produced by one of the following general methods: (i) By the oxidation of the corresponding aro- matic alcohols and aldehyds. (2) By hydrolysis of a corresponding nitril. (3) By the oxidation of the side chain of a cyclic hydrocarbon containing such. The general reactions may be exemplified by equations showing the production of benzoic acid" (i) CeHs.CH^OH -I- 2O, = CgHs-COOH -|- H,0. benzvl alcohol benzoic acid (2) CeH,.CIK) + O = CoH,.COOH. benzaldchyd (2) C«H,.CN + 2H.,() - C^Hj.COOH + NH.,. DERI\ATIVF,S OF BENZOIC ACID. 483 The most common method of producing benzoic acid is the third one — oxidizing a side chain of a hydrocarbon; thus, by the oxidation of toluene by dilute nitric acid: CeHs.CH3 + 30= CeH^COOH + H.O. toluene. Properties oj Benzoic Acid. — Glistening colorless needles, melting at 121° C. and boiling at 250°; sparingly soluble in water, freely in the organic solvents. Benzoic acid is also produced from "hippuric acid" as well as toluene; but in pharmacy for internal use, o«/y that suhlirned jrom benzoin should he employed: Benzoic acid is used as a preservative in foods, but its use should be prohibited, in that it is converted into phenol by the liver and acts as a cumulative systemic poison. Tests. — (i) Aqueous solutions of benzoic acid and its soluble salts give with ferric chlorid salmon- colored precipitates. (2) A benzoate dissolved in alcohol to which a few drops of H2S0^ have been added, upon heating, yields the characteristic odor of ethyl benzoate. (3) Silver nitrate added to a solution of a benzoate is precipitated as a crystalline silver benzoate which, on ignition, yields a residue of 47.1^;,' of silver. DERIVATIVES OF BENZOIC ACID. THE ESTERS.— These can be prepared b.\- methods analogous to the paraffinic esters. METHYL BENZOATE, CeH^.COOCHg, is a 484 PHARMACEUTIC CHEMISTRY. colorless oil, boiling at 199° C. and having a fra- grant odor. Synonym, "niobe oil." ETHYL BENZOATE, CeHs.COOQH,, a fragrant licjuid, boiling at 212° C. BENZYL BENZOATE, CoH^.COO.CeHs, is found naturally in cinnamein (oil of balsam peru); may be obtained from l)enzyl chlorid and benzyl alcohol. BENZOYL CHLORID, C,.H5.CO.Cl, is obtained by treating benzoic acid with phosphorus j)enta- chlorid. It bears the same relation to benzoic acid that acetyl chlorid does to acetic acid and, like the latter, it is an important reagent in organic synthesis. It is a colorless oil with a very irritating odor, and boils at 198° C. With water it is gradually decom- posed into benzoic and hydrochloric acids. BENZOIC ANHYDRID is produced when IjcnzoyI chlorid is treated with .sodium benzoate. It is a crystalline substance, melting at 42° C, and has the formula (CeH5.CO)20. The monovalent benzoyl group has the formula C„H..CO. BENZAMID, C„H5.CO.NH„ is a typical example of an aromatic amid. It can be produced in much the same way as acetamid of the fatty compounds: CeH, COOC.H^ + NH3 = C6H,.CO.NH, + C^Hj.OH. ethyl benzoate benzamid. Eenzamid occurs in sparingly soluble crystals, melting at 130° C. When heated with alkalis it is decom})osed, yielding ammonia and a corre- sponding salt: CcIIs.CO.NH, + KOH = CeH.COOK -I- NH3. HALOGEN DERIVATIVES OF BENZOIC ACID. 485 BENZONITRIL or phenyl cyanid, CeHj.CN, can be prepared by treating benzamid with dehydrating agents: CeHj.CO.NH^ = C 6H5.CN + H^O. benzo nitril. It may also be prepared from an anilin derivative — diazobenzene chlorid — by treating it with cuprous cyanid {Sandmeyer^s reaction): C6H5.N2CI + CuCN = C6H5.CN + CuCl + N2. benzo nitril. Benzonitril has the odor and appearance of nitro- benzene, but it boils at 191° C. HALOGEN DERIVATIVES OF BENZOIC ACID.— Benzoic acid is attacked by the halogens, although not so readily as the hydrocarbons. The following are the more important products: META-BROMBENZOIC ACID, C6H,.Br.C00H, melting at 155° C. ORTHO-BROMBENZOIC ACID, C\H,.Br.COOH, melting at 147° C. PARA-BROMBENZOIC ACID, CeH,.Br.COOH, melting at 251° C. All the above acids last mentioned are made by oxidizing corresponding bromtoluenes with nitric acid. When nitric acid, in presence of sulfuric acid, acts on benzoic acid, the following nitro derivatives are obtained: ORTHO-NITROBENZOIC ACID, CeH^.NOj.- COOH; melts at 147° C. META-NITROBENZOICACID.CeHj.NOa.COOH; melts at 141° C. 486 PHARMACEUTIC CHEMISTRY. PARA-NITROBENZOIC ACID, C.H^.NOjCOOH; melts at 238° C. ANTHRANILIC ACID is orthcj amidobenzDic acid, ^„/COOH(i) ^«"^\NH2 (2). It is produced by boiling indigo with caustic alkali. When heated with sulfuric acid, benzoic acid is converted into mono-sulfol)enzoic acid, Ortho-sulfobenzoic acid is obtained by o.xidizing toluene ortho-sulfonic acid. This acid treated with ammonia yields suljo-henzo-imid, commonly known as "saccharin,^' ghicin, guraniose, etc.: /SO^OHCi) , NH = ^«"%CQ0H(4) ^ ^^"^^ ortho-sulfobenzoic acid ^«"^\CO/^" + 2H,0. saccharin SACCHARIN (benzosulphinidum), benzosidfinid, is about 450 times as sweet as sugar, and one gram of it will afford the sweetening ecjuivalent to i pound of granulated sugar. It is. used for this purpose and in this proportion to sweeten the jood oj diabetic patients. Its use as a sweetener of ordi- nary foods should be prohibited, as its use is produc- tive of bad effects on the plasma of the blood. There are three isomeric toluic acids (o. m. p.), which may be produced by o.xidizing the corre- sponding three xylenes with nitric acid; thus: r TT /C^^.i(^^ -4- ^O ^ r H ^^^3 4-H O TOLUIC AND PHTHALIC ACIDS. 487 ORTHO-TOLUICACID.CgH./^^Qj^j^ , melts at 103° C. META-TOLUIC ACID, C^H, . ^Jj^^j^ , melts at 110° C. PARA-TOLUIC ACID, CgH^C^^^^^jj , melts at 180° C. All the toluic acids are crystalline and all resemble benzoic acids, and each, like benzoic acid, furnishes a corresponding chlorid, amid, anilid, nitro acid, etc., by the usual methods. The three phthalic acids analogous to the fore- going have the graphic formulas: COOH COOH COOH ^ COOH r' ' I ■ I COOH COOH phthalic acid melt- iso-phthalic acid terephthalic acid ing-point, 213° C. melting-point, (sublimes without 300° C. melting) The PHTHALIC ACIDS above can be obtained by treating corresponding toluic acids with potassium permanganate in alkalin solution: r H -^^^3 4- oo — r H ^ COOH TT Q ^«"*\COOH + 3^ - '-e^ix COOH +^2'-'- When strongly heated, phthalic acid yields: PHTHALIC ANHYDRID, CgH^C^^Q^O, melting at 128° and boiling at 284°. PhthaUmid is obtained 488 PHARMACEUTIC CHEMISTRY. from the anhydrid by heating it with ammonia. It melts at 229° C. CUMIC ACID, para-isoi)ropylbenzoic acid, C3H7.- Cgll^-COOH, is oljtained Ijy the oxidation of cuminol. UNSATURATED AROMATIC ACirS. The fol- lowing are representatives: Phenylacetic acid, CoHs.CHjCOOIT, melting at 76.5°- Phenyl propionic acid, CeH5.CH.,.CH2.COOH, melting at 47°. Cinnamic acid, C«H,.CH:CHCOOH, also called phenylacryUic acid belongs to the class of unsaturated aromatic acids. It occurs naturally in the balsamic resins — tolu, peru and styrax — and may be syn- thetically prepared by '' Perkins' reaction.''' This last is also a general method for the preparation of the unsaturated aromatic acids, and depends upon the heating of an aldehyd (either aliphatic or aromatic, depending upon the product desired) with the sodium salt of a fatty acid and its or some other anhydrid. The heating at 180° is continued for several hours. Condensation occurs, splitting off water, which is absorbed by the anhydrid. The anhydrid is thus converted into an acid which liber- ates the corresponding acid from its sodium salt. Cinnamic acid is produced by the above reaction from a mi.xture of benzaldehyd, acetic anhydrid and anhydrous sodium acetate, which is heated to 180°. (i) C6II5.CHO+ CH3CO.ONa = C6li5CII.CII.,.CO.ONa OH. sodium phenyl-lactate THE HYDROXY ACIDS. 489 C«H, which occurs naturally in oil of (2) C6H5.CH.CH.CO.ONa + (CH3C0).0 = [ I acetic anhydri d OHH (3) C6H,.CH:CH.COO H + CH3CO.ONa + CH3COOH. cinnamic acid. Cinnamic acid is readily soluble in hot water; it melts at 133° C. and sublimes at 300° C. THE HYDROXY ACIDS include the important— SALICYLIC ACID, ortho-hydroxy benzoic acid, 'OH (2) XOOH(i)' wintergreen (gaultheria) as a methyl ester (methyl salicylate). It can be obtained (i) by fusing salicin with caustic soda; (2) by boiling oil of winter- green with potassium hydroxid solution, whereby potassium salicylate is formed. Methyl alcohol being liberat.^d. /COOK ^\OH (3) by heating phenol with caustic soda in a cur- rent of carbon dioxid — " Kolbe's synthesis ". QH^. O.Na + CO. = C .H^O.CO.ONa sodium phenolate When this is heated to 1 forms: O.CO.ONa H CeH,^^g^^"-HKOH: C«H + CH3OH. .sodium phenyl car- bonate. C, sodium salicylate OH CO.ONa sodium phenyl carbonate sodium salicylate. 490 PHARMACEUTIC CHEMISTRY.. Thus, the high heat effects the intramolecular change. Sodium salicylate is decomposed with sulfuric acid, and salicylic acid is set free. Properties. — Salicylic acid occurs in fine, white, sparingly soluble crystals melting at 155° C. and readily soluble in the organic solvents. It is a valuable external antiseptic and a preservative, but unsuiied for internal administration. For this later purpose only its sodium salt, which has been pre- pared from the oil of wintergreen, should be em- ployed. The same may be said of all its other salts. Tests. — With ferric chlorid soluble salicylates give a violet-red color (distinguished i in 500,000 parts). SALOL is the phenylester of salicylic acid, CgH^./ p..., TT ? phenyl salicylate; it is obtained when salicvlic acid is heated alone to 210° C: ' /OH _p„/OH •\COOH~'^«"^\COO.C6H5 H2O; also— (2) By heating phenol with salicylic acid in the presence of phosphorus oxychlorid: 3CeH,(^^^^^^ + .sCeH^OH + f OCI3 = phenyl salicylate. Properties. — A white, crystalline, tasteless powder, converted in the body to phenol and salicylic acid by the pancreatic juice (it is insoluble in the peptic juices), and excreted by the urine as such. It possesses an aromatic odor, is insoluble in water SALOPHEN, SALIPYRIN, ORTHOFORM. 491 and melts at 43° C. Owing to its low melting- point and insolubility in the stomach, it is used for the coating of enteric pills. COOCH3 SANOFORM, CgHj— OH , is di-iodo-salicylic methylester, prepared by acting on the oil of winter- green with iodin. Insoluble in water, soluble in alcohol; it melts at 100° C. SALOPHEN, acetyl par a-amido phenyl salicylate, C6H,(OH)COO.C6H,NH.COCH3, a substitute for salol, it splits in the intestines into acetyl para- amido-phenol and salicylic acid. It melts at 187° C. SALIPYRIN is obtained by heating together 57.7 parts of antipyrin with 42.3 parts of salicylic acid, cooling and crystallizing from hot alcohol. Spar- ingly soluble, it melts at 92° C. NIRVANIN, a hydrochlorid of diethyl-glycocoll- amido-oxybenzoic methyl ester. It is used for pro- ducing local anesthesia as a substitute for cocain which is more toxic, also used in dental practice in 2 to 5% solutions. It has the formula /NH.OCCH,N(CH5)2(s) C6H3— 0H(2) ■\COOCH3(i) ORTHOFORM is related to nirvanin in properties, but is more toxic. It is the methylester of amido- /NH^Ci) hydroxy benzoic acid = CgHa— 0H(2) \C00CH3(4). 492 PHARMACEUTIC CHEMISTRY. ASPIRIN is acetyl salkylk acid, C^^/^QQ^^f BETOL is the naphlliol ester oj salicxlic acid, C H /^^" METHYL SALICYLATE, ^\^4(^(jq q^ - i^ the proximate principle found in the oil of gaultheria (wintergreen) and oil of betula. It can be obtained synthetically by distilling a mixture of salicylic acid, methyl alcohol and sulfuric acid. For flavoring purposes methyl salicylate (methylis salicylas), oil of gaultheria and the oil of betula may be said to be identical; for internal administration, however, only the last two should be used. Among the dihydroxy (dioxy) benzoic acids, the ■following may be mentioned. PROTOCATECHUIC ACID, C6H3(OH)2.COOH4- H2O, is one of six isomeric dihydroxy benzoic acids. It is found in many of the commoner resins, coloring matters, also in many tannins. It has the structure: COOH HO HO proto-catechuic acid, melt- ing-point, 199° C. ■ COUMARIN is the ivfier ester (lactone) of ortho- CU: Cli livdroxv, cinnamic acid, C,iHj:' 1 ; it oc- \o— c = o TRIHYDROXYBENZOIC ACIDS. 493 curs in very white crystals, possessing a very fragrant odor of woodruff, tonka bean and new-mown hay, of which it is a constituent. It is prepared from salicylaldehyd by the Perkins reaction, and is much used in perfumery and soaps; it blends well with aubepine and heliotropin, and melts at 67°. TRIHYDROXYBENZOIC ACIDS.— Among these but two, gallic and ellagic acids, are of importance. GALLIC ACID, C6H2(OH)3COOH. It is pre- pared by exposing moistened nutgalls to the air, when, by influence of a certain peculiar fermenta- tion, tannin is converted into gallic acid. It can be prepared from gallotannic acid, of which it is an anhydrid, by boiling it with dilute acids. It can be separated from gallotannic acid because it is soluble in aqueous ether. Gallic acid occurs in colorless crystals, melting at 220° C, readily soluble in hot water, less so in cold water. Tests. — (i) With ferric chlorid a deep blue ink is produced. (2) With potassium cyanid a pink precipitate is produced, which fades on standing, but reappears on shaking. (3) It does not precipitate gelatin (distinction frpm the tannins). ELLAGIC ACID is a yellow, crystalline, insoluble substance, closely related to gallic acid and found together with certain tannins, as in sumac, etc. DERMATOL is the basic bismuth gallate, Bi( OH),- C«H2(OH)3C02; a yellow, insoluble powder. 494 PHARMACEUTIC CHEMISTRY. AIROL is the oxyiodid of basic bismuth gallate, CgH2(OH)3Bi (^ ; a greenish, voluminous, insol- uble powder. THE TANNINS. This name, as well as that of "tannic acids," is applied to a large number of substances which have the property of forming insoluble compounds with the albumin of the raw hides by which they are absorbed. The ordinary "tannic acid" is the monobasic gallotannic acid, obtained from nutgalls (which contain 50% of tannin); chemically, it is digallic acid; i. e., a, condensation product of two molecules of gallic acid with the elimination of one molecule of water. And in reality, upon heating tannic acid, gallic acid is produced: Q,H,oO, + H,0 = 2C,H,0,. tannic acid gallic acid. TANNIC ACID (acidum tannicum), HC,^H,o09, gallotannic acid, or digallic acid. Prepared from nutgall by maceration with water and e.xtraction with ether. When heated in presence of moisture by chemical reaction it is converted into gallic acid. Light yellowish, amorphous powder; strongly astrin- gent taste; soluble in 0.34 part water and in 0.23 part alcohol, in i part glycerin with heat, freely in dilute alcohol; insohible in ollur soheiits; with ferric chlorid it produces bluish-black color which upon addition of lime-water is converted into bluish- 495 white and, with excess of lime-water, pinkish. It precipitates gelatin, alkaloids and metallic salts, and with potassium chlorate and other strongly oxidizing agents, it is explosive. When in solution, it forms ink with iron salts, and its preparations should not be brought in contact with iron vessels or spatulas. (Preparations: CoUodium stypticum, glyceritum, troche, unguentum.) OH OH OH Structure: ^^ OH HO ^^ ^^ OH OH COOH HO OH CO— O— CO gallic acid tannic acid (digallic acid). In the arts it is used as a mordant for certain dye- stuffs, and in the manufacture of inks; but for the tanning of leather cheaper varieties of tannin are employed. OTHER TANNINS. Tannin is a substance peculiar to the vegetable kingdom and widely distributed. Various modi- fications of it are known. Thus in nutgall, as gallotannic acid, in oak as quercitannic acid, and in catechu, krameria and cinchona as catechu, kramero- tannic and cinchotannic acid, respectively. They are composed of C, H and O in varying propor- tions. Tannins are usually amorphous; soluble in water, alcohol and glycerin. Their solutions are ,12 496 PHARMACEUTIC CHEMISTRY. acid in reaction and precipitated by most of the metallic salts and the alkaloids. When boiled with dilute acids they split into glucose and phlobaphene, being therefore regarded as glucosids, their chief property being that they form insoluble compounds with gelatin and, therefore, are used in tanning of leather. They are astringent when applied to mucous membranes, and upon this depends their therapeutic value. With iron salts the tannins produce characteristic colorations from green to blue-black, the different shades allowing of their being identified and distinguished. Other important sources of tannin are among the following: SUMACH, leaves of, Rhus coriaria and Rhus glabra. OAK, l)ark of, Quercus alba. MYROBALANS, fruit of Tcrmuuilia chchiilo. CUTCH, extract of the wood of Acacia catechu. HEMLOCK, bark of Abies canadensis. POMEGRANATE, bark of Piinica granatum. CHESTNUT, Iwrk of Castanea vesca. TANNING is the process of treating hides uifh tannin, to prevent putrejactive changes and to render the so-produced leather permanently flexible. Tanning is effected by first soaking the raw hides in milk of lime to remove the hair and at the same time to swell the skin. The lime is ne.xt dissolved out by soaking the skins in "old tan liquor" (containing lactic and citric acids — produced by fermentation) or in fermenting dung. The skins are then digested THE GLUCOSIDS. 497 (steeped) in "tan liquor" — an aqueous extract oj tannin, which precipitates the albumin of the skin, which is absorbed by the skin, rendering it insoluble flexible and porous — or leather. During the past few years the tanning of leather has been effected by other substances; thus, chrome alum has made the "chrome-tanned" American leather famous for its good wearing and elastic equalities. Other chromates and formaldehyd have also been successfully used. THE GLUCOSIDS. The term "glucosid" or "glycosid" is applied to a class of proximate principles which may be regarded as ethers chemically. The term glucosid was applied to these, owing to the fact that they are readily hydrolized into "glu- cose" when warmed with dilute acid or alkalin liquids, and in this respect they differ from the true ethers; also, by the enzym.es: if one of these is of albuminous nature, glucose is formed. The foregoing class of tannins are frequently classed with the glucosids. For convenience we will discuss the neutral principles under this head. The neutral principles include: aloin, chrysarobin, emodin, elaterin, santonin, picrotoxin, podophylo- toxin. The glucosids include: arbutin, salicin, strophan- thin, quercitrin, amygdalin, sinigrin and the glucosids of d gitalis. 498 PHARMACEUTIC CHEMISTRY. They all contain C, H and (). While some contain also N in addition, and others S. Thus, amygdalin, CjoHjyNOn, is nitrogenized, while sinalbin, CjoH^jNzSjOig, and sinigrin, C,oHjpNS^,- KO9 + H2O are sulfurated glucosids. They are nearly all insoluble in water, though readily soluble in alcohol. Their English names end in "in," the Latin in "iniiui." To distinguish' them jrom alka- loids ending in "ine," Latin "ina." The neutral principles are solid, crystalline sub- stances derived from plants. They are composed of C, H and O; insoluble in water, freely soluble in alcohol, sparingly in ether and chloroform. They differ from the glucosids in not being split into glucose, and from alkaloids in that they are not precipitated by tannin and other alkaloidal reagents. Sometimes they are classed as ''bitter jirinciples," on account of their taste. ALOIN (aloinum) Cj^HigO^, obtained from several varieties of aloes, chiefly Curacoa aloes. Prepared by -extracting aloes with acidulated boiling water, concentrating and crystallizing from warm, dilute alcohol. A crystalline powder of yellowish color; soluble in 65 jjarts water, 10 parts alcohol. Used in pills as a cathartic. Dose, 0.06. Preparation: Pil. laxat. comp. ELATERIN {elaterinum), C^o^^js^^^v Obtained from elaterium, which is deposited in the juice of the fruit of ecbalium elaterium. Minute white crystals, sparingly soluble in the solvents, except in 22 parts chloroform. Used in the official lo'/J NEUTRAL PRINCIPLES. 499 trituration as hydrogogue cathartic. The Clutter- bucks elaterin is the most reliable. Dose, 0.03. PICROTOXIN {picrotoxinum) is soluble in 240 parts water and 9 parts alcohol. Used in o.ooi gm. doses. SALICIN {salicinum), QgHjgOy, a glucosid ob- tained from several species of the salix and populus by digestion with lead oxid, extraction with water, purification with charcoal and crystallization. Silky needles, soluble in 21 parts water, 71 parts alcohol, insoluble in other solvents. Colored violet with ferric chlorid; sulphuric acid dissolves it with red color. Saliva resolves it into saligenin and glucose. Used in rheumatism. CuHigO^ -f H2O = C.Hi.Og + Cb H,.OH.CH,OH . saligenin SANTONIN {santoninum) , CisHj^O,, the inner anhydrid or lactone of santonic acid. Obtained from santonica by boiling levant worm-seed with calcium hydroxid, decomposing this salt with HCl, dissolving in hot alcohol, purifying with charcoal and crystallizing. Flat, prismatic crystals; soluble in 35 parts alcohol, 78 parts ether, 2.5 parts chloro- form. Turns yellow when exposed to light. Used in the official troche, containing 0.03 gm. in each, as a worm remedy. CHRYSAROBIN (chrysarobinum), a neutral prin- ciple extracted from goa powder. A pale, orange- yellow powder, darkens on exposure, soluble in 150 parts boiling alcohol, insoluble in water. Used in ringworm and other skin diseases. Dose, 0.03 gm. 500 PHARMACEUTIC CHEMISTRY. With oxidizing agents it is oxidized to chrysophanic acid. Prei)araliun: Unguentum 6%. STROPHANTHIN (strophanihinum), €,^^^^0^^, a glucosid or mixture of glucosids ol^taincd from stro- phanthus. Yellowish-white, crystalline powder, in- tensely bitter, very soluble in water and dilute alco- hol, insoluble in other solvents. Used to regulate heart action. Dose, 0.0003 K^- (t^u grain). Glucosids obtained jrom Digitalis purpurea: DIGITOXIN, CjsH^bOio, most active glucosid of digitalis leaves. White, crystalline powder, almost insoluble in water, soluble in alcohol and chlorolorm. Dilute acids decompose it into digitoxose, CgHj^O^ (a-sugar), and digitoxigenin, C22H32O.,. Dose. 0.00025 gm. (jh) grain). DIGITALIN, "i'^rewc/?," yellow amorphous powder, soluble in 2000 parts of water, very soluble in alco- hol and chloroform; consists chiefly of a glucosid, physiologically identical with digiloxin. Dose, 0.00025 gm. (y^-fl grain). DIGITALIN, ''German,^' yellowish-white powder, so'iib'e in water and alcohol, almost insoluble in ch'oroform; consists of a mixture of glucosids digi- talin, amorphous digitonin and digit aleln. Dose, o.ooi gm. (^j grain). DIGITALIN cryst. (Kiliani), identical with digi- tonin cyst. C27H4G^\4+SH2<^) almost insoluble in water, ether and chloroform. Physiologically in- active. DIGITALEIN, while amorphous powder, soluble in water and alcohol. A heart poison. NEUTRAL PRINCIPLES. 50I QUERCITRIN, CgeHggOjo, is present in Qiiercus tinctoria, tea, which, when hydrolyzed, yields a yellow dye, quercetin, and rhamnose, a sugar. EMODIN, CjjHjqOs, is present in Cascara sagrada, rhubarb and buckthorn bark. ARBUTIN (C12H16O7), found in bearberry leaves, yields hydroquinone and dextrose on hydrolysis. PICROTOXIN (CgoHg.O^a), found in Cocculus indicus, is highly poisonous. PODOPHYLLOTOXIN, C.^\^^S^^ + HjO), occurs in the resin of Podophyllum pel latum. CHAPTER XXXVI. THE GUMS. The gums are a class of amorphous substances frequently produced by the degeneration of the tissue of plant cells. The gums are divided into two classes: (a) The soluble or true gums, of which ACACIA or gum arabic, an exudation from Acacia Senegal, is a type, and (b) insoluble gums, which absorb large quantities of water with which they form jellies, but do not dissolve in it. To this second class belongs TRAGACANTH, from Astragalus giimmijer and other varieties of astragalus. ACACIA, chemically, is the arabinate salt of cal- cium and magnesium, a complex compound, pre- cipitated by alcoholic and ethereal tinctures, ferric chlorid, borax and lead salts. Its mucilage (Muci- lage acacia?) and powder are useful for suspending resinous, fatty or oily substances in aqueous media, forming emulsions. TRAGACANTH, chemically, is composed of basso- rin or tragacanthin, C^^W^o^io^ ^'^d calcium salt of gummic acid, which is not identical with arabic acid. Tragacanth occurs in flakes which can be pulverized when heated to 50° C. It is also employed in making emulsions and troches and for suspending insoluble powders in water. 502 RESINS. 503 RESINS are solid, usually amorphous, vegetable products with a conchoidal fracture. Soluble in alcohol, fixed oils, but not in water. Transparent or semitransparent, readily fusible and inflamma- ble. Some contain acids, and with the alkalis are capable of forming soaps, others are not saponifiable. Composition: Resins are mi.xturcs of different compounds of C, O and H. Shellac, for example, consists of 5 different resins and a coloring matter. Amber is a mixture of several resins with succinic acid. Sandarac consists of three insoluble resins and a bitter principle soluble in water. They are, ■ perhaps, the oxidation pro- ducts of volatile oils, judged from the fact that they are always associated with it in plants. Some resins, like amber, elemi, copal, dammar, kauri gum, shellac and asphalt, all unofficial, are used for the manufacture of varnishes; others, Ukeresina, guaiac, mastic, are used in medicine. They are divided into: (i) Resins obtained from oleoresins, as the residue from distillation. (2) Natural exuda- tions. (3) Prepared resins obtained by precipi- tating extracts of drugs with acidulated water, sometimes called '"resinoids." (4) Balsamic resins or "balsams." Member of the first class RESINA, common rosin or colophony, is the residue after distilling the volatile oil (oil of turpentine) from the oleoresin of turpentine (pitch). Melting point, 100° C. Dark, amber-colored mass, soluble in alcohol, ether and the oils. Contains abietic anhvdrid. Used mainlv for varnishes, ointments. 504 PHARMACEUTIC CHEMISTRY. soaps and plasters. (Off. Prep.: Ceratum Resina- Comp.) NATURAL GUMS include all the varnish "gums" mentioned above and that of GUAIACUM (Guaiaci resina). It is found in the heart wood. A very complex substance consisting of guaiacic acid, guaiac yellow, guaretic acid, betaresin, also small pro- portion of gum. It is soluble in alcohol and caustic potash, but insoluble in turpentine and benzol. The powder is whitish, but turns green on exposure to light and air, the depth of the color being indicative of the age of the powder. Used as a stimidant, diuretic and alterative. Sometimes given as an emulsion in rheumatism and in pastils for sore throat. (Off. Prep.: Tincture and Ammoniated Tr.). MASTIC (mastiche). Obtained from vertical incisions into the bast layer of the trunk of the tree and the larger branches. Contains masticJiic acid about 90%, soluble in alcohol; masticin, soluble in hot alcohol, a trace of volatile oil. Mild astringent, also used for cements and varnishes. (OlT. Prej).: Pil. Aloes and Mastiches.) Kauri gum and amber (succinum) occur as fossils, so does asphallum. THE OLEORESINS arc of vcgetab'le origin and consist of mixtures in various proportions of resins with volatile oil, therefore partaking of the characters of both. They are divided mto: (i) Natural oleo- resins to which belong the turpentines, copaiba and the pitches. (2) Prepared oleorcsins, also called pharmaceutic oleoresins, made b\ extracting oleo- resinous drugs with ether or acetone. They are semi- solid preparations made from the following drugs: THE OLEORESINS. S05 aspidium, capsicum, cubeb, lupulin, pepper and ginger. Copaiba, commonly called "balsam of copaiba," is an oleoresin derived from various South American species of copaiba by Ijoring holes in the heart wood. Light to brownish, viscid liquid; specific gravity, from 0.95 to 0.99, increasing with age. Soluble in absolute alcohol and the other solvents; insoluble in water. Evaporated on the water-bath, it should yield 50% residue and develop no odor of turpentine. There are four varieties of copaiba: Rio Janeiro and Maranham, containing volatile oil and resin in nearly equal amounts. The Para variety contains between 70 and 85% of volatile oil, while Maracaibo contains from 20 to 40% of volatile oils and correspondingly more resin. This last variety is the best for making the mass with magnesia, and is also preferred therapeutically, the resin being most valuable and the. oil com- paratively inert. Adulteration. — This oleoresin is frequently adulterated with gurjun balsam, which is detected by dropping four drops of copaiba upon a mixture of i c.c. of glacial acetic acid and four drops of nitric acid with which the adulterant forms a coloration. The fixed oils, like castor, cottonseed, turpentine and other oleoresins, are detected by the sticky residue on evaporating the volatile oil. Volatile oils, like turpentine and pine-needle oils, are detected by their odor w^hen warmed. The oleoresin contains volatile oil, copaibic, oxycopaibic or metacopaibic acids, various resins and a bitter principle, soluble in water. Used as expectorant. 5o6 PllAKMACKUTIC CH K.MISTRV. diuretic ;ind stimulant in the form of the mixtures (N. F.), emulsion, paste or pill. The turpentines are olcoresins from trees belonging to the' Pimifcce and Conijcrce. All their volatile oils are terpenes. TEREBINTHINA, commonly called "gum," "pitch" or "common turpentine." It is a concrete oleoresin, obtained as an exudation from Pinus palustris and other species of pinus. Yellow- ish, opaque, tough masses, brittle in the cold, of tere- binthinate odor and taste, contains about ^o% of volatile oil and about 66% of resin. Used as diaphor- etic, diuretic, stimulant and astringent; externally, in ointments and plasters. Its principal use is for the preparation of oil of turpentine by distillation, the residue being common rosin. TEREBINTHINA CANADENSIS, a semiliquid oleoresin obtained as an exudation from the balsam frr (Abies balsamea). "Canada, balsam" and "balsam of fir" are two of its most common synonyms. Transparent, yellow- ish, viscid liquid, hardening with age, contains volatile oil and two resins. It is used as a stimulant, diaphoretic, diuretic; in ointment form for frost- bites; in microscopy as a mounting "medium. The unofficial turpentines and pitches embrace the following: Terebinthina venata (Venice turpentine, Terebinihina argentoratensis, Strassburg turpentine) closely resembles Canada balsam. Terebinthina chia (Chian or Cyprian turpentine), appearance like balsam of fir; balsamic, fennel-like odor. PIX BURGUNDICA (Burgundy pitch U. S. P. '90), obtained from -l/>/V.v excelsa or N\)rway spruce THE BALSAMIC RESINS. 507 fir. Semitransparent or opaque, hard, but yielding without fracture. Fix canadensis (hemlock pitch U. S. P. '80) resembles the previous one. Fix liquida, tar product of the destructive distillation of the wood of various species of pine. Viscid, black- ish-brown, semifluid, with empyreumatic odor, and terebinthinate taste. Very complex composition. It contains the guaiacols and cresols. It is slightly soluble in water, more so in alcohol, fixed and volatile oils and solutions of the alkalis. Used as local stimulant and expectorant. (Preparations: Syrupus, o.5^( ; Ung., 50%)- From this by distilla- tion is prepared OIL OF TAR {Oleum picis Hqiiida;), specific gravity, 0.97. Readily soluble, yielding acid solutions. Dose as stimulant and expectorant, 0.2 c.c. Allied to this, OIL OF CADE (Oleum cadinum), a product of the dry distillation of the wood of Juniperus oxycedrus. A brownish, dark liquid with a tarry odor and taste. Insoluble in water, partially in alcohol, completely in ether. Used in skin diseases. THE BALSAMIC RESINS or "balsams." Bal- sams are oleoresins or gum-resins containing either benzoic or cinnamic acids or both. The official balsams are benzoin, peru, tolu, and styrax. Besides these, we have the balsam of the sweet gum tree (liquidamber styracifiua of the southern United States and the dragon's blood (Resina draconis), exudation from a palm fruit of Daemonorops draco, native in Malay Archipelago. It contains both ben- zoic and cinnamic acids. Astringent and stimulant, emploved for coloring varnishes and in plasters. 5o8 PHARMACEUTIC CHEMISTRY. BENZOIN (benzoinum), gum benzoin. A Ijab samic resin obtained from styrax benzoin, a tree native to Sumatra, Java and Siam. It exudes from incisions made through the bark of tree. Several varieties known as the Sumatra benzoin, the Siam benzoin (having an agreeable, vanilla-like odor) and Penang benzoin, similar to Sumatra, more fre- quently resembling styrax. Benzoin contains from 12 to 20% of benzoic acid which is obtained by sublimation, cinnamic acids, various resins. Some varieties contain vanillin. Soluble in 5 parts of warm alcohol, also in solutions of the hydroxids of alkalis; insoluble in water. Antiseptic expecto- rant. (Preparations: Tr. Benz. 20%; Tr. Benz. Comp., \o%; Adeps Benz., 2%). When the tincture is prescribed in aqueous solutions, it should be emulsified with acacia before dispensing. BALSAM OF PERU (Balsamum peruvianum), de- rived from Toluifera pereinie. A viscid, dark brown- colored liquid, of an agreeable, vanilla-like odor and a bitter, acrid taste. Completely soluble in absolute alcohol, chloroform or glacial acetic acid. Only partially soluble in ether and petFoleum benzin. Completely soluble in 5 parts alcohol, with slight opalescence. Specific gravity, 1.14 to 1.15. Con- tains about 6o7o of volatile oil; resin, 32%; cinnamic acid, benzoic acid and benzyl alcohol. Frequently adulterated with alcohol, fixed oils, copaiba, turpen- tine and rosin. Used in ointments internally as stimulant and expectorant, also in ])crfumery. BALSAM OF TOLU (Balsamum tolutanum). A GUM RESINS. 509 balsam obtained from Toluifera balsamum (Central America). A yellow-brown solid, vanilla-like odor, with a mild, aromatic taste. Completely soluble in alcohol and chloroform, solutions of fixed alkalis and ether. Insoluble in carbon disulfid and benzin. Contains benzoic and cinnamic acids, two different resins, toluene and benzylic benzoate and cinnamate. Adulterated with the turpentines which, with sul- furic acid, bleach, while the true balsam turns cherry- red. Expectorant and stimulant. Used also in per- fumery. (Preparations: Tincture (20%); Syrupus and Tincture Benz. Comp.) STYRAX, storax. A balsam prepared from the wood and inner bark of liquidamber orientalis, a semiliquid, grayish, sticky, opaque mass. Upon standing, separates into layers. Has an agreeable odor and a balsamic taste. Soluble in alcohol, ether and carbon disulfid. Insoluble in cold benzin, but hot benzin dissolves out the styracin and cinnamic acid, which are deposited in crystals on cooling. Composition: Benzoic and cinnamic acids, styracin, storesin, resin, etc. Used as stimu- lant, diuretic, expectorant (in Tr. Benz. Comp.). GUM RESINS comprise those milky exudations of plants which contain gums, soluble in water, and resins, insoluble in water, but soluble in alcohol. Some contain volatile oils; therefore, they are divided into (i) Those containing volatile oil: ASAFETIDA (asafoetida). Exudation product from Ferula foetida and other species of Ferula. Native of Afghanistan and Turkistan. Obtained 5IO PHARMACEUTIC CHEMISTRY. by incision. Several varieties are known, like the amygdaloid, coming in irregular pieces or tears imbedded in a sticky, brownish mass. The liquid, which is a sticky, semifluid or more or less impure mass, which darkens on exposure, and the stony variety, which contains a large proportion of calcium sulfate and other impurities. Asafetida possesses a strong, garlic-like odor, bitter acrid taste, forms a milky emulsion with water, which turns yellowish with ammonia. Asafetida should yield not less than 50% of matter soluble in alcohol. Composition: vola- tile oil, 3 to 9%; gum, 20 to 30%; resin, 50 to 70%, and various impurities. Stimulant, antispasmodic, expectorant. (Preparations: Emulsum, 4%; Tr., 20%; Pil. Asaf.) Usually administered in pills, suppositories or emulsion. MYRRH (myrrha).— Spontaneous exudation from bark of Commiphora myrrha (Arabia). A dusty reddish or brownish mass of irregular tears; aromatic odor; bitter, acrid taste. It yields a brownish-yellow emulsion with water. Its alcoholic solution acquires a purple coloration with nitric acid. It is composed of gum, 40 to 6o'>^ ; resin, 25 to 40%; a trace of vola- tile oil and a bitter principle. Used as a stimulant, expectorant. (Preparations: Mixt. Ferri Comp., Pil. Aloes et Myrrh, Tr. Aloes et Myrrh). Usually administered in pill or powder or as an emulsion. The unofficial gum resins containing volatile oil are: Bdellium, very s\m'i\ar io myrrh; olibanum (frankin- cense), which contains about 30% of gum, 70^1 of resin, with volatile oil and i)ittcrs. Used in plasters GUM RESINS. 511 and fumigations; AniDioniaatDi, ammoniac (sjjon- taneous exudation product from the stem of Dorema ammoniacum U. S. P. '90), contains gum, 18 to 25%; resin, 70%; volatile oil, from ^ to 4%. Used as expectorant and stimulant for making Emuls. Ammon. Oppoponax, similar in properties and uses to ammoniac; Galbamim, spontaneous exudation, of which there are two kinds — the tear and lump galbanum. Its alcoholic solution, treated with HCl, turns purplish. It contains 20% of gum, 66% of resin, volatile oil, 6 to g'oj . Used as antispasmodic, stimulant, expectorant. (2) Gum resins containing no volatile oils: CAM- BOGIA (gamboge), obtained by making incisitms into the bark of Garcinia hanburii (Cochin China and Siam). Cylindrical sticks, sometimes hollow, con- choidal fracture, orange-red in color; odorless; acrid, unpleasant taste; the dust being sternutatory. Good quality yields a bright yellow powder, also bright yellow emulsion with water. Composition: gum, 16 to 20%; resin, about 80%. Used, com- bined with other drugs, as a hydragogue cathartic. (Preparation: Pil. Cathart. Comp.) SCAMMO- NIUM (scammony). The dried milk-juice of Con- volvulus scammonia (Western Asia). Obtained by cutting off the top of the root and collecting the milky juice. Dark greenish or l)lackish, irregular masses, l)reaking with an angular fracture. .\ resinous luster; the powder has a greenish cast. With water it \ields a dark greenish emulsion. Odor, checsc-like; taste, acrid. Composition: Gum, 5 to i59( ; resin, 33 512 PHARMACEUTIC CHEMISTRY. 80 to 9o'/c ; frequently adulterated with starch, chalk and various resins. Used as hydragogue cathartic. (Preparation: Resina scammonii). Usually adminis- tered in pill form. ELASTICA (rubber, caoutchouc). The prepared milk-juice of Hevea brasiliensis and of various other species of Hevea. Known in commerce as Para rubber. Obtained by evaporat- ing the milk-juice and exposing the semi-solid to fire and smoke until hard masses or "hams" are formed. Brown or brownish-black, internally lighter colored; insoluble in water, dilute acids, solutions of alkalis or alcohol; but soluble in chloroform, benzene and benzin, carbon disulfid and oil of turpentine. Lighter than water. Melting-point, 125° C, and at this temperature dissolves in petrolatum. With carbon disulfid it iorms a mass used as rubber cement. The 50% solution in petrolatum with lead plaster constitutes the rubber adhesive plaster. Mixed with sulfur and heated, it is rendered insoluble and un- affected by heat, or vulcanized (vulcanite or ebonite or hard rubber). EUPHORBIUM, an official ex- udation from incisions in the stem of Euphorbia resinifera or cactus-like shrub, is native to Morocco. It has an acrid taste, a brownish-yellow color, occurring in globular or irregular masses; not completely emulsified with water nor completely soluble in the simple organic solvents. It contains euphorbin, a resin, 18% of gum and impurities. Used as a violent purgative. NAPHTHALENE AND ITS DERIVATIVES. 513 NAPHTHALENE AND ITS DERIVATIVES. Naphthalene has the formula QoHg, a melting- point of 80° C. and a boiling-point of 218° C. It occurs in that portion of coal-tar which boils between 180 and 220° C, and which on cooling solidifies to a mass of crystals constituting crude naphthalene. Crude naphthalene is warmed with caustic soda, to remove phenol, next with a little sulfuric acid, to remove the bases, distilled with steam, separated and dried. It is sometimes further purified by sublimation. Properties.- — Naphthalene is insoluble in water, but dissolves readily in the organic solvents. By heating it to 130° with dilute nitric acid, it is oxidized to phthalic acid; hydriodic acid will gradually reduce naphthalene to dihydrid, CjoHjo, tetrahydrid, CioHjj, and hexahydrid, C^^Yi^^. With nascent chlorin it forms additive products: Dichlorid, CjoHgClj, tetra- chlorid, CioHgCl^, etc. Structure. — Various structural formulas were from time to time advanced for naphthalene; thus: CH CH HC I C<',^lcH CH CH Bamberger's centric formula 514 PHARMACEUTIC CHEMISTRY. H H I I C C H— C C C— H I II I H— C C C— H C C I I H H Erlenmeyer's formula Both of the above formulas have something in their favor; however, the Erlenmeyer formula, based upon Kekule's alternate single and double bond- benzene rings, is now generally accepted. From the Erlenmeyer's formula for naphthalin it may be regarded as two Ix-nzene rings having two carbon atoms in common. ^^\/\ The more compactly written formula is now generally used in the text-books on organic chemistry. Naphthalene gives two mono-derivatives which arc distinguished by the prefixes a (alpha) and P (beta). The structural formula for nai)htha- Icne shows this, on numbering the carbons in (he nucleus; thus: SYNTHESIS OF NAPHTHALENE. 515 . The sulistitution can either take place at one of the carbon atoms which is attached to one of the two carbon atoms common to both rings; thus, I, 4, 5 and 8, giving an alpha compound, while 2, 3, 6 and 7 give a beta compound. Synthesis. — Naphthalene may be synthesized by- passing phenylbutene bromid over red-h(_)t lime. CgHs.C.H.Br^ = 2HBr + QpH^ + H2 naphthalene Homologues. — Two methylnaphthalenes and two ethylnaphthalenes are known. Of these ^-methyl- naphthalene. CH3 is a solid, melting at 32° C; the other thi-ee compounds being liquids with high boiling-points. When naphthalene is heated with sulfuric acid, two mono-sulfonic acids are formed. These acids, fused with caustic alkalis, similarly with the produc- tion of phenol from benzene, yield two hydroxy- naphthalenes : 5i6 PHARMACEUTIC CHEMISTRY. OH and OH alpha-naphthol melt- ing-point, 95°; boil- ing-point, 282° C. beta-naphthol melting- point, 122°; boiling- point, 288° C. THE NAPHTHOLS are hydroxids of the monoval- ent radical naphthyl, CjoHy, and bear the same relation to naphthalene that phenol bears to benzene. ALPHA-NAPHTHOL, CioH^OH, is used as an antiseptic and antifermentative, but being more toxic is less used than — BETA-NAPHTHOL, CioH^— OH, is generally used as an antiseptic in cutaneous disorders as an oint- ment. It is soluble in aqueous solutions of alkali hydroxids, forming metallic derivatives. ORPHOL, Basicbeta-nafhthol bismuth (CioH-OjjBi + 3H2O, a brownish powder possessing an aro- matic odor and containing about 72.5% of bismuth oxid. Used as intestinal astringent. ^COOH EPICARIN, C«H3— OH , is beta-naphthyl- ^CH^.O.C.oHj ortho-oxymetatoluitic acid, a brownish-yellow powder, sparingly soluble in hot water, but freely in alcohol, ether and acetone. It is employed similarly to /3-naphthol in skin diseases, but is said to be superior to it. NAPHTHYLAMIN COMPOUNDS. 517 NAPHTHYLAMINS.— The two naphthylamins, CjqH^.NH,, resemble anilin closely and are prepared by similar methods. ALPHA-NAPHTHYLAMIN, CioH^.NH., is ob- tained by heating ammonia and a naphthol with calcium chlorid to 250° C: C,oH,OH + NH3 = C10H7.NH2 + H2O. a naphthylamin melting-point, 50°; boiling-point, 300° C. It can also be obtained by reducing a nitronaph- thalene with nascent hydrogen. It occurs in crystal- line needles (Zinin, 1842). BETA-NAPHTHYLAMIN is best obtained by acting on iS-naphthol with ammonia under pressure. i3-Naphthylamin melts at 112° and boils at 294° C. NITRONAPHTHALENES.— By the direct nitra- tion of a-naphthol only the a-nitrona phthalene is obtained. It has the melting-point 61° C. The second nitro group likewise enters the alpha (i and 4) position, consequently it is not possible to prepare beta-nitronaphihalene by any direct method. Beta-nitronaphthalene is obtained from i3-naph- thylamin by the diazo-reaction. It melts at 79° C. NAPHTHALENE SULFONIC ACIDS, C10H7.SO3H, are formed when naphthalene is heated with strong sulfuric acid. The ordinary naphthalene sulfonic acid is a mixture of both the alpha and beta varieties. These vary in ratio to each other with the temper- 5l8 PHARMACEUTIC CHEMISTRY. ature of the reaction; thus: At a temperature not exceeding 80° mostly the alpha is formed, while at 160° C. the beta acid predominates. When fused with potash, these acids are decom- posed into the corresponding naphthols. NAPHTHYLAMIN SULFONIC ACIDS are em- l)loyed in the manufacture of such azo dyes as congo red — henzopiirpiirin, etc. NAPHTHIONIC ACID (i and 4) is obtained jjy heating in vacuo a-naphthylamin sulfate to 130° C; it has the formula CioH,.(NH2)S03H. MARTINS' yellow' is obtained by acting with strong nitric acid u])()n a-naphthol. The sodium salt, C,oH-,(()H).>()Na,H20, is used as a dye. NAPHTHOL YELLOW is ol)tained by acting with strong nitric acid ujxm a-naplithol-lrisulfonit- acid. The potassium salt is used as a dye. NAPHTHAQUINONES.— Two isome;s are known, of which a-najjhthaquinone corresponds to benzo- (juinone in properties. Their formula is CjoHgC^^- NAPHTHOIC ACIDS.— Naphthalene forms also the unini])ortant carboxylic acids, of which the two known ones will l)e given: (/-NAPHTHOIC ACID, CioHj.COOH, obtained by the hydrolysis of the a-cyanid CiqH^.CN; melts at 160° C. /i-NAPHTHOIC ACID, prepared from the /3-cyanid ; melts at 182° C. NAPHTHALIC ACID, C,oHe(COOH),, has the two carbowis in per: position (both in alj)ha i, 8). STRUCTURAL FORMULAS. Structural jormulas: OH 519 OH naphthalene, CioHs NH, o-naphthol C10H7.OH 6-napthol C10H7.OH NO2 NH. a-naphthylamin C10H7.NH2 6-naphthylamin a-nitronaphthalene B10H7.NH2 CioH7.N02 OK SO3H NO, SO,K NO, 6-nitronaphthalene a-naphthalene-sul- naphthol yellow C10H7.NO3 fonicacid CioH6(N02)20.Na C10H7.SO3H O O II II COOH COOH 6-naphthaquinone napthalic acid CioH6(COOH)2 a-naphthaquinone C10H6O2 520 PHARMACEUTIC CHEMISTRY. ANTHRACENE.— Anthracene, Cj^Hjo, occurs in that fraction of the heavy coal-tar oil which boils between 230° and 270° C. It is found as a light brown deposit, mixed with phenanthrene and carhazole. This sediment is separated by means of a filter press and the residue is washed free from oil, with naphtha. The product contains, and is known in commerce as, " 50 per cent." anthracene. From this crude anthracene alizarin and other valuable dyes are made. By mixing the crude anthracene with solid potas- sium hydroxid, it combines with carbazole, forming potassium carbazole, and the residue with carbon disulfid, with which phenanthrene (more soluble) can be washed out. Properties. — Anthracene occurs in colorless plates, having a bluish fluorescence, melting at 213° and boiling at 351° C. It is insolul)le in water, but readily soluble in the organic solvents. Structure. — Naphthalene is frequently regarded as a condensation of two benzene rings with the loss of two carbon atoms; just so, anthracene may be regarded as a condensation of three benzene-rings with the loss of four carbon atoms: \, c C II I c c or, more compactly, Synthesis. — Anthracene may be synthetized by SUBSTITUTION PRODUCTS OF ANTHRACENE. 52 1 passing petroleum through red-hot tubes; also by heating benzyl chlorid with aluminum chlorid: 3C6H5CH,C1 = C6H4 = CH-CH = C6H , + Ce H, CH, + HCl. anthracene toluene SUBSTITUTION PRODUCTS.— Three isomeric monosubstitution p oducts of anthracene are pos- sible; these can be distinguished by prefixing their names with the Greek letters a, /3 or 7: a y a also fifteen disubstitution products. ANTHRAQUINONE.— With the exception of an- thraquinone and its hydroxids, the products of an- thraquinone are of little pharmaceutic importance. Anthraquinone, C14H8O2, is prepared by oxidizing anthracene with chromic acid. It occurs in yellow, insoluble prisms, which dissolve in benzene; melt at 285° C, and at higher temperatures sublime. With hydriodic acid it is reduced to anthracene. Structure: O CO 522 PIIAR.MACEUTIC CHEMISTRY. HYDROXYANTHRAQUINONES.— The «- p-dihy- droxyanthraquinone is the very im])()rtant dve alizarin, .CO. CgH/ ^CeH,(OH),. Alizarin occurs naturallv \co/ in the madder root (Rubia tinctoria) as ruberythric acid, and has from early times been employed as a red dye-stufif. Alizarin is one of the most important dyes in the entire gallaxy of dyes. It is also one of the most important synthetic economic discoveries (Perkin, Graebe and Liebermann, 1868) of all the times. It was originally synthesized l^y fusing dibrom- anthraquinone with caustic potash: /CO\ Qh/ ;CeH.Br. + 2KOH = \co-^ ' ' dibromanthraquinone QH/ )C6H..(0H), + 2KBr. ^CO^ alizarin. Synthesis. — The above method, proving too costly, was later relinquished for another process, consisting in the heating of anthraquinone with pyrosulfuric acid to 160° C. and forming anthraquinone-beta- suljonic acid: CO. CeH,( >CeH, + H,SO, = '^CO' anthraquinone .CO. C„H,( )C«H3 - SO3H + H,0. ^CO-^ anthraquinone b-sulfonic acid ALIZARIN. 523 This acid is neutralized with sodium carbonate and the so-formed sodium salt is fused with caustic soda and a little potassium chlorate, the chlorate furnishing the necessary oxygen: CO CeH,/ )C6H3.S03Na + NaOH + = CO C,H,( >CeH,(OH)3 + Na2S03. ^CO-^ alizarin The alizarin formed is dissolved out in water, digested with milk of lime, and insoluble calcium alizarate is filtered out. This calcium salt is next decomposed with hydrochloric acid, whereupon the alizarin precipitates as a brown, amorphous powder. It is sent into commerce as a 10 or 20% alizarin paste. Properties. — Alizarin is insoluble in water, but dissolves in the caustic alkalis with a violet color, forming corresponding alkali salts. This violet color is bluer in the presence of NaOH, and redder if NH^OH is present. With the metallic compounds it forms insoluble compounds of different colors, called "lakes;" thus, with the ferric salts a "violet lake"; with chromium salts, "brown lakes"; with aluminum salts, "bright red lakes"; with barium chlorid, "deep purple lake"; with stannous chlorid, "orange lake." These alizarates can be precipitated with ammonium hydroxid, collected, dried and used as pigments; thus, with aluminum acetate the familiar turkcy-rcd is obtained. 524 PHARMACEUTIC CHEMISTRY. In 1880, $8,000,000 worth of alizarin had been made artificially. Had this same amount of alizarin been made from madder root, the cost of the neces- sary material alone, irrespective of labor, would have been $28,000,000. Thus a saving of $20,000,- 000 had been effected in one year by one synthetic chemical method. Alizarin orange and alizarin blue are some of the alizarin derivatives. PURPURIN (i, 2, 4), trill ydroxya nth raquinone, occurs, like alizarin, in the roots of the various species of rubia, and it can be. obtained from alizarin by heating it with manganese dioxid and sulfuric acid. It occurs in yellowish-red, slightly hot-water-soluble prisms. In the presence of mordants, it dyes fabrics a yellowish-red color. ANTHRAPURPURIN (i, 2, 2'), trili ydroxya nthra- quinone, is obtained by fusing 1,2' disulfonic acid with caustic soda and potassium chlorate. FLAVOPURPURIN (i, 2, 3'), trihydroxyanthra- quinone, is formed in a similar way to anthiapurpurin from I, 3' anthraquinone sulfonic acid. Structure: O \/ \/ anthracene anthraquinone PHENANTHRENE. 525 O OH OH O OH OH O O OH HO OH OH O OH HO OH O anthrapurpurin flavopurpurin PHENANTHRENE, C,,U^„ is isomeric with anthracene, and is found in coal-tar associated with it. It occurs in colorless needles, melting at 99° and distilling at 340° C. Phenanthrene is regarded chemically as diphenyl C12H10, in which the two ortho- positions are linked by the group — CH = CH thus: 526 I'HARMACEUTIC CHKMISTRY- CH c^}tzz::^^c ch HC( > V ;cH CH CH CH CH or, more compactlv, Phenanthrene is of little commerical or pharmaceutic importance. CHAPTER XXXVII. HOMOCYCLIC AND HETERO-CYCLIC SUBSTANCES. All the ring (cyclic) structures thus far studied have been composed of similar atoms, namely, carbon. Thus, benzene, naphthalene, anthracene, have only carbon in their rings; such substances are called homocyclic. There are known, however, compounds having two or more dissimilar atoms in their rings, these are known as heterocyclic substances. An important example of this latter class is had in pvridin, C,H,N. PYRIDIN, C5H5N, is a colorless liquid with an odor like tobacco smoke and a boiling-point of 115° C. Pyridin occurs in bone oil, "Dippel's oil," pro- duced by the destructive distillation of bones. The fraction passing at 150° is collected and converted into pyridin ferrocyanid, which is purified bv recrystallization and decomposed by the alkalis. Pyridin is soluble in water. When treated with metallic sodium in an alcoholic solution, it is con- verted into piperidin, CjHuN. With the halogens it forms substitution products, and under certain conditions also addition products. 34 527 528 PHARMACEUTIC CHEMISTRY. With acids pyridin forms staljle crystallizable salts by addition, thus proving its amin nature. It is not acted upon by nitrous acid, nor is it converted into isonitril by alcoholic potash and chloroform, proving that it is a tertiary amin, having the structure H \ H— C ^/3C— H H— C «C— H pyridin, boiling-point. or, more compactly. /\ N This structure is verified by its synthesis from penta-methylene-diamin hydrochlorid. By rapidly heating this latter salt, it loses one molecule of NH^Cl, becoming converted into piperidin, the hexahydrid of pyridin. This, by mild oxidation, is converted to pyridin: CH2 HX CH, H2C CH., I I NH.,NH.,.HC1 pentamcthylene diamin-hydrochlorid H,C H..C CH, CH, CH, NH jiiperidin PYRIDINCARBOXY ACIDS. 529 CH HC ^^ CH HC CH. N pyridin Regarding the situation of the carbon atoms to the nitrogen atom, it is apparent that it should form three isomeric mono-substitution products, and in reality three such isomerids are known in the three pyridincarboxy acids; thus: (a) picolinic acid (;3) nicotinic acid (7) isonicotinic acid. COOH. COOH COOH N N N Pyridin has several homologues: The methyl pyridins, known as picolins; dimethylpyridins, known as lutidins; and trimethylpyridins, known as collidenes. QUINOLIN, C9H7N (Gerhardt, 1842), like pyridin, occurs in bone oil and coal-tar oil. It can be synthesized by boiling together a mixture of anilin, nitrobenzene, glycerol and sulfuric acid, removing the undecomposed nitrobenzene by steam, rendering alkalin and separating the quinolin with a current of steam. 530 'HARMACEUTIC CHEMISTRY. Quinolin is a colorless oil with an unpleasant penetrating odor, sparingly soluble in water and boiling at 239° C. It combines, like pyridin, with the acids, and exhibits all the other properties of tertiary amins. Upon oxidation, quinolin is first converted into tetra- and finally into decahydroquinolin. With potassium permanganate it is oxidized into quino- linic acid. COOH COOH COOH COOH N quinolin, boiling- point, "^32 C. quinolin ic acid, (a.|3. pyridin dicar- boxy acid.) ISOQUINOLIN, C9H7N, occurs, like (juinolin, in bone oil (Hoogewerfif). It was first obtained from crude quinolin by fractional crystallization of the sulfate. It occurs in crystals, melting at 21° and boiling at 237° C. NH isoquinolin, boil- ing-point, 237' C. carbazole, me 1 1 j n g ■ point, 338° C. THE ALKALOIDS. 53 1 CARBAZOLE, QjIigN, occurs with anthracene in anthracene grease. Melting-point, 238°; boiling- point, 351° C. THE ALKALOIDS. Some of the basic substances already mentioned, as pyridin, quinolin and isoquinolin, are usually considered as the simpler alkaloids. Alkaloids are now frequently classified with refer- ence to their parent body; i. e., body of which they are considered derivatives; thus: DERIVATIVES OF PYRIDIN, N Lobeline, C^^H^J^^j from Indian ttjbacco (Lobelia inflata). Sparteine, CijHjgNj, from broom (scoparius). Piperidine, CjHuN, found in pepper (Piper nigrum). Coniine, CgHj^N, found in poison hemlock (Conium maculatum), a liquid alkaloid, boiling at 167° C. Nicotine, QoHi^Nj, from tobacco (0.6 to 8%) (Nicotiana tabacum). Piperine, C17H19NO3, found in pepper (8%). Atropine, C17H23NO3, found in belladonna (Atropa belladonna), thorn-apple (Datura strammonium), henbane (Hyoscyamusniger). It melts at 115° C. Hyoscyamine, C17H23NO3, found associated with 532 PHARMACEUTIC CHEMISTRY. scopolamine in the plants of the deadly nightshade family. It melts at 108.5° C, and at this temper- ature becomes converted into the isomeric alkaloid atropine. Scopolamine, found in the plants of the "deadly nightshade" family and purported to constitute the bulk of the hyoscine of commerce, with which it is said 'to be identical. This last statement should be treated with some skepticism until more is known of the structure of these alkaloids; scopolamine melts at 198° C. Hyoscine, C^-^l^n^^O^, found in the plants of the deadly nightshade family. Homatropine, C,eH2iN03, an artificial alkaloid — tropine mandelate. The last-mentioned five alkaloids constitute the class of "mydriatic alkaloids," capable of dilating the pupil of the eye. Homatropine is deemed the most desirable, since its mydriasis wears off in twenty-four hours. Cocaine, Ci7H,jNOj, occurs associated with eight closely related alkaloids in coca leaves (Erythroxyl- lon coca). Cocaine also exerts a slight mydriatic action, but is chiefly employed as a local anesthetic. It melts at 08° C. DERIVATIVES OF QUINOLIN, N STRUCTURE OF QUININE. 533 Quinine, C^oHj^NjOj, found with utlier alkaloids in cinchona bark (Cinchona calisaya) and other varieties of cinchona (8 to io%) . It is a diatomic base and forms two classes of salts; melts at 177° C. Cinchonine, CjgHjjNsO, found associated with quinine (2.5%.) It is, like quinine, dibasic and forms two classes of salts; it melts at 250° C. Qiiinidine and cinchonidine are two other alkaloids of cinchona, distinguished from the former two by being dextrogyrate and forming soluble tartrates. Quinine and cinchonine are levo gyrate; and form sparingly soluble tartrates. To detect whether quinine or its salts are contaminated with the cheaper cinchona alkaloids, it should readily dissolve in ammonia water; the other alkaloids do not. Structure: C,oH,5(OH)N CH3O N quinine Morphine, CJ7H19NO3.H2O, found in opium (from Papaver somniferum) together with twenty other alkaloids, as follows; morphine, 10%; narcotine, 6%; papaverine, 1%; codeine, 0.5%; thebaine, 0.3%; narceine, 0.2%, etc.; separated by Sertiirner. It melts at 230°, and is a strong narcotic. Codeine, CjgHjiNOg, is a homologue of morphine, 534 I'llARMACEUTIC CHEMISTRY. and found associated witli it. It melts at 153° (". and is the most soluble of ojjium alkaloids. Strychnine, C21H22N2O2, found in the "dog-button" (Strychnos nux vomica) and other strychnos species. It melts at 284°, is a monacid base; sparingly soluble in water, readily in the acids. Very strongly poisonous, producing tetanus even in small doses. Brucine, C23H26N2O4, crystallizes in colorless prisms and melts at 178° C. Sparingly soluble, monacid base. Colchicine, C2iH22(CH30)N05, found in Colchicum autumnale. Amorphous alkaloid, melting at 147° C. When hydrolyzed, it yields a second alkaloid, ro/r/n- cein, C21H22OHNO5. Physostigmine, Ci5H2iN302, also called eserin; found in calabar bean (Physostigma venenosum). While the alkaloids of the deadly nightshade family are all mydriatic, the opium alkaloids are all myotic (contracting the pupil of the eye); but the strongest myotic is found in physostigmine. Pilocarpine, C11H16N2O2, found in jaborandi leaves (pilocarpus). It is a deliquescent alkaloid, very soluble, used to produce diaphoresis. " Veratrine, C37H53NO11, found in cevadilla seed (Asagrea otTicinalis), and not from veratrum, as is erroneously supi)Osed. It is poisonous and a power- ful sternutatory. THE DERIVATIVES OF XANTHIN have been con- sidered on page 3Q2, and embrace theine, caffeine which is official as well as its mi.xture with citric acid (50';, each), the "citrated" laffein, guaranine, DERIVATIVES OK PYRROL. 535 koldii'uic and theobromine. The salicylate of theo- bromine is employed as a diuretic under the name of Diuretin. DERIVATIVES OF PYRROL, C,H,:NH; pyrrol is found in bone oil (Dippel's oil) together with HC— CH II II pyridin. It has the structural formula, HC CH: NH lodol, C^I^NH, is produced by acting with iodin and caustic potash on pyrrol. It is a brown, odor- less powder containing about 89% of iodin, and used as a substitute for iodoform. Pyrazol, CgH^No, has been obtained artificially from hvdrazin and chlorhvdrin. Its structural CH— CH II II formula is N CH and the melting-point, 70° C. NH. Antipyrin, Ci^HjjNjO, phenazone, is an artificial alkaloid made from phenylhydrazin and aceto acetic ester. By heating these, condensation occurs and a ketone, phenylmethyl pyrazolone, is formed. This ketone, heated with methyl iodid and potassium CH3.C = CH hvdroxid, yields antipvrin, CH3.N CO , soluble \/ N-CeH , antipyrin, melting- point, 113° C. and a very incompatible febrifuge. 536 I'HARMACEUTIC CHEMISTRY. DEFINITION AND DISCUSSION. The alkaloids may be considered as basic carbonaceous amins which combine with acids similarly to ammonia to form crystalline salts. There are vegetable alkaloids, like morphine; animal, as ptomain, and artificial alkaloids, as quinolin. They are the most powerful of the organic principles. They all contain, in addition to nitrogen, C and H and, with few exceptions, O. When heated with alkalis, ammonia is given off (distinction from glucosids). Alkaloids are usually named after the generic name of the drug. The suffix "ine" (Latin, "ina") distinguishes them from glucosids and other principles. Some alkaloids, like morphine, which has been named in honor of Morpheus (the god of sleep), and the alkaloids of the cinchonas are named arbitrarily; thus, pelletierine has been named after the discoverer, etc. They may be divided into amins and amids; the amids containing oxygen, the amins not containing it. The amins are liquid and volatile alkaloids and embrace coniine, sparteine, nicotine, lobeline, while all the amids-are solid bodies. They are all insoluble in water, but soluble in alcohol, chloroform, benzin, benzol, amylic alcohol, kerosene, and some in ether. They do not exist naturally in the free state, but as acids or neutral salts comb'ned with some acids peculiar to the plants; thus, as quinine and cinchonine, combined with the kinic acid peculiar to cinchona. The opium alkaloids are combined with meconic acid, as meconates and the EXTRACTION OF ALKALOIDS. 537 strychnos alkaloids of mix vomica, etc., combined with igasuric acid, while other alkaloids are com- bined with such common acids as tannic, citric, tartaric, etc. Alkaloidal salts: when forming salts, the alkaloids do not replace the hydrogen of acids, thus showing the terms "sulfate," "chlorid," etc., to be incorrect when applied to an alkaloidal salt. They should be named "hydrosulfate," "hydro- chlorid," respectively, etc. Ammonia hydrochlorid (ammonium chlorid) may serve as a type of the formation of alkaloidal salts; thus: NH3 + HCl = NH3.HCI or NH.Cl. Q7H19NO3 + HCl = Ci^H^gNOa.HCl. GENERAL METHODS OF EXTRACTION.— (i) When the native alkaloidal salt is soluble in water and the alkaloid itself insoluble, strong alkali is added to a decoction of the vegetable substance. It neutralizes the organic acid with which the alkaloid is associated, precipitating the alkaloid in an impure state. (2) When the native alkaloidal salt is insoluble in water, a very dilute acid is used in the extraction of the drug, so that it combines with an inorganic acid to form a salt. This solution is decomposed with an alkali, yielding the alkaloid as a precipitated salt. The process may be divided into six steps; thus: (i) Solution; (2) precipitation; (3) re-solution; (4) decolorization (with animal charcoal or lime) ; (5) purification; (6) crystallization. The salts of the alkaloids are soluble in water, some 538 PHARMACEUTIC CHEMISTRY. arc very freely soluble in alcohol, l)Ut most of them are insoluble in ether and chloroform. Tests. — (i) Phosphomolybdic acid (Sonnenschein's Reagent) produces yellow precipitate. (2) Nitric and sulfuric acids color many alkaloids reddish. (3) Sodium phosphotungstate (Schieblcr's) produces precipitates soluble only in HjPO^. (4) Potas- sium mercuric iodid (Mayer's) forms yellowish pre- cipitates insoluble in acidulated aqueous solutions. (5) Cadmium potassium iodids (Marme's) gives a gelatinous precipitate. Other alkaloidal precipi- tants are picric acid and the following chlorids: Hg, Pt, Au, Sn, lead acetate and subacetate, Lugol's solution, KI and the iodids of Hg, Bi and Zn. With tannin insoluble tannates are formed (antidote). Among the unofficial alkaloids, aspidospermine, from quebracho bark; berberine, from berberis and hvdrastis; coniine, from conium seed; delphinine, from staphisagria; emetine and ccpha^line from ipecac; gelsemine, from yellow jasmine, and jervine and veratralbine, from veratrum (white and green), may be mentioned. THE ANIMAL ALKALOIDS, PTOMAINS AND LEUKOMAINS.— The i)tomains, as the cadaveric alkaloids are called, were so named by Selmi in 1870. This authority demonstrated that such changes as putrefaction, fermentation, etc., of the albuminous bodies are productive of alkaU)id-like bodies; that these may be either liquid or solid, volatile or fixed. PTOMAINS are formed bv the ])utrefactive changes 05 % a 05 .rio .TV « O fe o NNONOiNMiNOOOO oooo oooooooooooo oooo O o o cJ nm^^iUH l,!li' M^ ^% Ji' "?;£<- S.oSoovo^'S^ ^ -t" °,ss w u-,^-1 H^ ^ ^-s^sss-Sf-^s ¥^|f = 5-5 ^; OO^ OcoNii-. ^„ o t^«^00 " ^t^^OO ro lO t^ ■ TfOO „ ro i$ VO o ^o^ o o '^.o c ffiO gffiffi w 5? ffiffi w "3 q5°„qqq§^"dgdo' ddgo + 6 "2:0 S K.§ 3 -^ffi fflKlfflffiffiW^^Iffi^IffiK WK^^ ffi^.W J^uuJuBy,uy.uc5 6u5icj u^o 6" S" 1 '^ oj ll .1 1 1 1? 5 a o o ■>.-5 « 3-0 -S „> ^-c c c d 13 rt « fj « M » "S -S .S .£ .£ .S & . rt « S O •s -a -s -s d c -g ^ e^ e- e^ & i 3 :§ ^ 1 3 "3 3 "3 "3 3 .S .S o ° o ° a^ o o CCO'O'O'O'U U ^ ^ ^ ^ <; UUU J3 ^ J3 ■SplOlWllB 1 -spioiBJii^ BUoqDuiQ -spioiBJip umido BOtlUOA xnN 5^ ??1? o'o'g' £-..J_5 5._ 8 8 8 O O O IT'S o' o' lo o' o o o o o 6 6 6 do 6 ^,66666666666 IS _o u :i| ::kI M-»MI»y = S ill III 3s"J?s|ii?=Jl < fe rt ^ o^<«u. --- g^o^cssfc":?^'^ o^oo 666 ^-6666666^-^9.9.^. ^ z^z^ ^^^^ z^ 5 -0 z ^^^ z 'z'z ;s ^„ ^^ ^ z :z ffi ^r-^I 4 K W 1 J.e'j: K K ffi K E %X X X X u^y- 666 o 6666666^6666 O .\tropina, Atropine sulphas, Hyoscyaminae sulphas, Hyoscyaminas hydrobromi- dum, Hyoscina; hydrobromidum, Homatropinae hydrobromidum Scopolaminae hydrobromi- dum. Aconitina, Caffeina, Cocaina, Cocaina; hydrochloridum, Colchicina, Hydrastina, HydrastininjE hydrochloridum Physostigmin;e sulphas, Physostigminse salicylas, Pilocarpin;e hydrochloridum, Pilocarf)in;e nitras, Sparteine sulphas. •SplOIE>llB OIlBUpXl^ I'TOMAINS, LEUKOMAINS AND TOXINS. 54T of the animal tissues, and may be harmless or poison- ous. Among the nonoxygenaled liquid ptoniains, the following are monamins: dimethylamin, tri- ethylamin and propylamin. Among the diamins: tetra-methylene-diamin {putrescin), C^HjjN,; penta- methylene-diamin (cadaverin), C5H14N2, and its isomer found in decomposing flesh — neuridin. Hydrocollidin, CuHjjN, is found in decomposing horse-flesh. Collidin, CgHjjN (trimethyl-pyridin), and the tetramethyl-pyridin (parvolin), C9H13N, are also important. The oxygenated ptomains of importance, besides the already-described neiirin and choMn, are: Gadinin, CyHjgNOj, found in putrid fish; niyli- toxin CgHj.NOj, found in poisonous mussels. Gautier (1880) announced that in the animal excreta poisonous alkaloids are found, and he named these "leukomains." LEUKOMAINS are basic substances formed by the retrograde metamorphosis in the human body. Leukomains include the xanthin bases; some are poisonous, some not. TOXINS are classed as ptomains, formed by the action of the pathogenic bacteria in the living body. The combined action of the above three classes of products has a deleterious effect on the human body, known as autointoxication. Autointoxication, there- fore, is due to the incomplete oxidation and excretion of these accumulated products in the system. 542 PHARMACEUTIC CHEMISTRY. ANTITOXINS are bodies found in the blood- serum, which have been developed there by the action of certain microorganisms in the body. They have the property of protecting the animal system against further infection by the same organism. This protection is known as immunity. THE PROTEINS. The proteins form the chief and constant organic constituents of the animal and, to a certain extent, plant bodies. Their composition is very complex and their structure unknown; they all contain carbon, oxygen, hydrogen, nitrogen, sulfur and phosphorus, and some contain iron. Proteins are amorphous, nonvolatile, nondiffusible, odorless, colorless and tasteless bodies. On destruc- tive distillation, they yield ammoniacal derivatives. When warmed with nitric acid, their aqueous solutions are colored yellow (xanthoproteic reaction); heated with mercuric nitrate in a solution of nitric acid, proteins turn red {Millon's reaction) ; boiled with sodium hydroxid solutions, upon the addition of a little cupric sulfate solution, proteins give violet-pink color [Biuret reaction); boiled Ti'///; glacial acetic acid, and undcrlaycd with strong H^SO^, proteins give a purple color at line of contact (Adamkiew-icz's reaction). Gelatin and peptone are examples of the proteins. Thev arc all distinguished by the ease with which tlicy undergo putrefaction. PUTREFACTION. 543 PUTREFACTION. Putrefaction is a fermentative change taking place in nitrogenous substances: Example (Meeker): Enzymes Peptones Nitrogenous products Basic Acidic Indol i Leucin Skatol Tyrosin Ptomains Nitrous acid. Ammonia, etc. etc.. Non-nitrogenous products Oxalic, lactic, butyric, phenylacetic and phenyl- propionic acids, phenols, hydrogen sulfid, hydrogen, methane, carbon dioxid, etc. Becoming finally, under sufficiently long-continued aerobic conditions: Carbon Water dioxid I Nitri acid Nitrogen 35 CHAPTER XXXVIII. THE TERPENES AND ESSENTIAL OILS. The terpenes arc volatile proximate princii)les of plants. Common oil of turpentine is the common- est type of the terpenes. Terpenes are hydrocarbons having an empiric formula, (CsHg)^. The following groups of terpenes are distinguished: 1. Hemiter penes, C^Hg. Example: isoprene in rubber. 2. Terpenes, C,oHig. E.xample: australcne in turpentine oil. 3. Sesquiterpenes, C^^^.^. Examples: cadinene and anbebin. 4. Diter penes, C^ffH^^. Example: Colo pliene — oxy- genated turpentine. 5. Polyterpenes,{Cioli^^)^. Exam\)\es: caoufchouc and gutta-percha. The terpenes are further subdivided into three classes, according to physical and chemiial })rop- erties. (i) PINENE CLASS.— This class embraces the colorless terpenes, having agreeable odors, boiling about 156°, and having specific gravities about 0.8. They are usually optically active; when treated with dry hydrochloric, hydrobromic or hydriodic acid, they add on one molecule of these acids. Thus is obtained pinene hydrochlorid, CjoHjg.HCl, known 544 LIMONENE CLASS. 545 as "artificial camphor." With bromin they form dibromids, and with nitrosyl chlorid, crystalline compounds; with iodin and sulfuric acid, pinene is converted into cymene. It occurs in varying quantities in many essential oils; the dextro-modification, australene, is found in the American turpentine (Pinus australis), while the levo-modification, lerebenthene, is found in the French turpentine (Pinus maritima). It boils at 155° C, and has the specific gravity 0.855, and is obtained by distilling turpentine resin (gum) with steam. Turpentine oil (Oleum terebinthinae) is employed in the manufacture of paints and varnishes. It absorbs oxygen, in time becoming resinified. It fulminates when mixed with iodin. (2) LIMONENE CLASS.— Members of this group are also colorless, very aromatic liquids, boiling at about 170°, having the specific gravity 0.8. These combine with two molecules of dry hydrochloric-acid gas, forming dihydrochlorids, while with bromin they form crystalline tetrahromids. Oil of lemon peel and phellandrene, occurring in certain eucalyptus oils, lime and citron oils, are types of the limonenes. They are optically active. Limonene is also called citrene, carvene and hesperidene. Both the pinenes and limonenes are cyclic compounds : 546 PHARMACEUTIC CHEMISTRY. CH, I ■ C -/\ HC CH^ I I HX CH^ CH I C /% C H3 C H, limonene. (3) MYRCENE CLASS.— But few of the myrcenes known. The chief difference between this and the above two classes lies in the fact that the myrcenes are unsaturated, open-chain hydrocarbons, = C^^S=^^)CH.CH,.CH:C.CH, CH:CH, myrcene. Myrcene is a constituent of bay oil, which is the class representative. Dipentene is the racemic (inactive) form of the pinenes. It is found in many essential oils and in turpentine, and can be made by mixing equal parts of the two active limonenes. SESQUITERPENES, C^^^^„ are the higher poly- mers of hemiterpenes and constitute an interesting group of terpenes. In that, some are cyclic and others not, some form additive products with HCl gas, others will not. Cadiitnic. from oil of cade; TERPIN HYDRATK AND C'AMPHKNK. 547 humulene, from hop oil, constitute the reactive ex- amples of the group, while clovene and caryophyllene, both from clove oil, are nonreactive examples. When oil of turpentine is exposed to the action of the air in the presence of alcohol and nitric acid, a crystalline compound, known as terpin hydralc, CioHi8(OH)2,H20 (terpini hydras U. S. P.), de- posits through the union of three molecules of water. It occurs in rhombic prisms, melting at 1 16° C. Ter- pene hydrate, upon boiling with dilute sulfuric acid, loses two molecules of water and is converted into terpineol, C,oHj7,OH, known as synthetic lilac or syringa oil, extensively used in perfumery. Allowed to stand 24 hours in contact with sulfuric acid, turpentine becomes converted into terebene (tere- benum U. S. P.). Terebene is an optically inactive mixture of dipentene, terpinene, cymene and cam- phene. It boils, when pure, at 170° to 185° C. Terpinene is an isomer of limonene, and so is ter- pinolene. Camphene can be obtained by saponification of pinene hydrochlorid. Camphene is a crystalline body melting at 49° C. When turpentine is sub- jected to distillation, the volatile portion which passes over with steam constitutes the turpentine oil, while the transparent amber-colored residue constitutes colophony or "rosin." This rosin consists mainly of a complex acid which is a derivative of phenanthrene, and called abietic acid, C18H27COOH. It melts at 146° C, dissolves entirely in caustic alkalis, con- stituting the "rosin soap" of commerce. 548 PHARMACEUTIC CHEMISTRY. POLYTERPENES, (CioHi6)n- These can be ob- tained by polymerizing turpentine oil with antimonyl chlorid. The most important are the class of rubbers. CAOUTCHOUC is contained in the sap of the India-rubber tree, (Hevea elastica). This milky sap hardens on exposure and constitutes "India rubber," specific gravity, o.q6. It vulcanizes with sulfur chlorid, constituting "vulcanite," ebonite, used for many useful purposes. The best variety of raout- chouc is para rubber (elastica U. S. P.). GUTTA-PERCHA.— The coagulated milky juice of dichopsis trees (Isonandra gutta). Specific gravity, 0.98. It is decomposed on melting. Nonelastic below 60°, but very soft at 100° C. It is soluble in benzol, chloroform, turpentine and carbon disulfid, with which it forms the rubber cement. Batata and chicle gums resemble gutta-percha closely. OXYGENATED CONSTITUENTS OF THE ESSENTIAL OILS. While the various terpcnes usually constitute the bulk (body) of the essential oils, their odors are due to some of the oxygenated carbon compounds, namely: Alcohols: Borneol, linalool, geraniol, citronellol, santalol, menthol, cincol. Esters: Hornyl acetate and otlior borneol esters; linalool esters, like the acetate; geraniol esters, like the acetate; methyl esters, like the salicylate. CAMPHOR, BORNEOL AND MENTHOL. 549 Aldehyds: Citral (geranial), citronellal; benzoic and cinnamic. Ketones: Menthone; carvone, methyl nonyl ketone and camphor. Phenols : Thymol, eugenol, carvacrol. CAMPHOR, CioHjgO, is obtained by boiling chips of wood from the camphor-tree (Cinnamomum cam- phora) in a vessel with a perforated dome into which the camphor sublimes. Camphor (camphora U. S. P.) is defined as the dextrogyrate modification of the saturated ketone obtained by sublimation from camphor wood Cinnamomum c. It has a charac- teristic odor, cooling taste and melts at 175° C. The melting-point constituting the safest test for its identity and purity. BORNEOL, CioHi7(OH), Borneo camphor, is found in all three modifications — dextro, levo and inactive. The common Borneo camphor is dextro- gyrate, melting at 203° and obtained from the wood of Dryobalanops camphora. MENTHOL, CioHi9(OH), mint camphor, is ob- tained from oil of peppermint (Mentha piperita) by chilling it. It is a secondary alcohol and yields menthone, a ketone on oxidation. Chemically, it is k ex a h ydroxycy mene : DISCUSSION AND DESCRIPTION.— The essen- tial or "volatile" oils have been so named after two facts: because they are "the essential odorous prin- ciples of plants "and because "they leave transient or volatile stains on paper," this distinguishing them 550 PHARMACEUTIC CHEMISTRY. from the fats. The essential oils differ from the n.xed oils in the following points: (i) In chemical composition: they are chiefly terpenes, and not esters of the fatty acids. (2) They range in boiling-points from 150 to 250° C, volatilizing without decomposition. (3) In their specific gravities they range from 0.83 to 1. 187. (4) Thev do not form soaps with the alkalis. (5) They are slightly soluble in water and in definite proportions of alcohol. They are also freely soluble in the organic solvents. Many of the volatile oils, in addition to C, H and O, contain also nitrogen; some contain also sulfur. According to these con- stituents, oils are frequently classified for pharma- ceutic purposes into : (i) Terpenes, like the oils of lemon, orange, neroli, bergamot, etc. (2) Oxygenated, like the oils of anise, cinnamon, clove, wintergreen, rose, etc. (3) Nitrogenated, like the oflicial oil of bitter almonds, peach kernels, etc. (4) Suljurated, like the volatile oil of mustard, garlic, asafetida, horseradish, etc. They fulminate with iodin; react powerfully v/ith nitric and sulfuric acids; are readily oxidized by the air, acquiring color, resinifying, etc., and should be preserved in cool, dark place, ])referably in small comjiletely filled bottles. Adulteration. — Volatile oils are frequently adulter- ated with alcohol, which is detected by turning milky ELEOPTENES. 551 U'iih water on agitation and b\- dissolving red anilin, which is insoluble in the oils. Fixed oils are detected by leaving a permanent stain on paper. Cheaper volatile oils can only be detected by the specific gravi- ties, by the optical rotation and more frequently by the sense of smell. Many of the oxygenated oils are mixtures of liquid and solid principles; the former being solvents for the latter. These liqiiid prin- ciples are termed eleoptenes; the solid principles, stearoptenes or camphors. Thus, menthol is the stearoptene or camphor of peppermint oil. Thymol and camphor are both stearoptenes; these congeal upon chilling the oil and can be separated from the eleoptenes. SAFROL, C10H10O2 (safrolum U. S. P.), the methylene ether of pyrocatechol found in sassafras and camphor oils, is a type of the eleoptenes. EUGENOL, QoHj^O, U. S. P., is an unsaturated aromatic phenol found in clove and pimenta oils. EUCALYPTOL, C,^Yi,^0 (cirfeol), is an inactive organic oxid, boiling at 176° C; specific gravity, 0.93. CAMPHORA MONOBROMATA, CioH^^BrO, the monobromated camphor of pharmacy, is a substitu- tion product of camphor and bromin. It is insoluble in water, soluble in other solvents, and used as a sedative. 552 PHARMACEUTIC CHEMISTRY. Structures: CH, CH- -CH CH, -CH- -CH„ H3C— C— CH I CH..-^ C CH CH. I CH3 camphene, CioHie H3C— C— CH3 CH(OH) CH3 CH, -CH- borneol. CioHit.OH -CH3 HX— C— CH, CH, -c = o I CH3 camphor, C9H16.CO PREPARATION OF VOLATILE OILS.— Volatile oils are prepared after t)nc of the five methods fol- lowing: (i) By distillation ivith steam; thus, the oils of peppermint, spearmint and rose are distilled from the coarsely comminuted drugs. The oils floating on top are separated. The condensed waters are sold as distilled "floral waters." (2) By expression; where the oil is readily separated, as in the case of the oils of orange, lemon and bergamot peel. (3) By extraction with solvents; in cases where the delicate oils would decompose with heat, they are extracted by macerating the flowers with odorless fi.xed oils or lard (enfleurage) from these they are dissolved out by alcohol which is distilled off' in PREPARATION OF VOLATILE OILS. 553 vacuum. Oils of jasmin, tuberose, etc., are obtained thus. (4) By distillation of oleoresins; thus, the oils of turpentine and copaiba are obtained. (5) By destructive dist illation are obtained the oils of tar and cade, from pine and juniper-wood, respect- ively. 2i2 1' S% ; hydrocyanic acid, 1 2, Mor more than 4%- laO; anisic aldehyd, sic acid; methyl chari- 0i U il § Ml -1^ b|5 •3 •50 1 IMpi^ li iiaiiciwPiSs mummmmimi b cq ^ - - ._ ^ ^ . J J J H C) O^iJ ^ Uo> to U . ■* t30 vO in OS \C I^ ^ ° ° ? 0000 0000 - o> 00 w M M 00 00-' d d M ^1 II lis PI 2„ Is 1 1. H 1 li g^ ^' 1 ■ 11 -OS =s rt'^M le ■^ |e 1^1 >. "-^ '^'^ e§^ s ;g E grt ■S -1 l^s . I-" -i d v^ J, ol S >> « f^ > c C S w ■c .2 "m C- ? II J 1 1 It s 8 .2, ^ 1 ii 1 11 1 1 li li p 1 ft IJ W O s f 1 *j > 3 "S s ^ I -i « 3 ^^ ll 0, 1 ■ 1 (3 w 1 -s 1^ "So 2I 1 8 2 "S 1 ^0 13 k 2 IP til ■5 11 1 i 2 % ^ n If eSs SS •" - E E EE a-- 3 a c 3 33 33 V.O 0) (U <3 a a ii O O 00 5 5 55 m 111 ^ K c ^6 -^ c •S'^o 11 ,: ^b^*^ i SS "►thsSm o.oJii'SS^^ -g-c e»;^0-^ g^^ ::c 3.Hgd„■ Oi-lQ H O a> >. o-g 00 00 00 !> o O ►-O o o o o ^2 I u .5 a o d fresh flowers (Lavendula vera) fresh peel (Citrus limonum) leaves of tops (Mentha piperita) leaves and tops (Mentha viridis) leaves (Myrcia acris) seed (Myristica fragrans) oleo resin (Pix liquida) p p i a -o .2 S e 1 ^ II 2: 1 P "S O Oleum lavendute florum (oil of lavender flowers) Oleum limonis (oil of lemon) Oleum menthse piperita (oil of pep- permint) Oleum mentha; viridis (oil of spear- mint) Oil of bay Oleum myristicse (oil of nutmeg) Oleum picis liquidae (oil of tar) 5 e a ^ "o S 1 o- 5 ^ p ^ •5. s -E E 5 ^s* OKJ K|| ^"1 ^„ 2 g O- fe C « II o s <^ OilO Cfl 20- u So 2 S£52oqS|-3 r- M O mo o o o\ 00 00 ON M 11 o o o o d I in -2- ^ E c 52 > ■S o i 2c II r. >. e F EE i^ ■3 E E?^ E'«E 3 a 3 Ji o o OO O O O O O CHAPTER XXXIX. THE PURIFICATION OF ORGANIC COMPOUNDS. There are three methods used in the purification of organic compounds: 1. Crystallization | . , r i- i ^ " . . > m the case of solids. 2. bul)limation j 3. Distillation — in the case of liquids. Solvents. — In the case where solids are to be puri- fied by crystallization and recrystallization, deter- mine the best solvent ; one which dissolves the most of the salt while hot, and which, on cooling, crystallizes out the dissolved salt. Some solvents are inflam- mable; others are not. In cases where inflammable solvents are used, employ the steam-bath or water- bath to heat the same and never the naked fame. Goggles should be used to protect the eyes while working with volatile solvents. While subliming substances, the same should be mixed with about an equal quantity of pure sand which has been heated previously for about ao minutes. The funnel used should have its mouth covered by a filter paper and the beak stopped up by means of a paper plug. Some substances sublime without previous lique- faction, other liquefy first. (Try naphthaline, CjoHg, and benzoic acid, CglI,.,COOH, as e.xamples). Distillations in vacuum and with steam arc often 558 ORGANIC ANALYSIS. 559 employed in the purification of liquids. The con- densed vapor is frequently saturated with the dis- solved substance and can be "salted out" by satu- rating the water with ordinary salt, and " taken up" with a volatile solvent like ether. The solutions of solids or liquids are frequently filtered through bone- black before crystallizing or separating them and are thus freed, from impurities. BEHAVIOR OF ORGANIC SUBSTANCES WITH IMMISCIBLE SOLVENTS. Upon agitating the substance with distilled water acidulated with 2% of H^SO^, and adding half its volume of an immiscible solvent (ether, chloroform, or benzene), the following are extracted: (i) In the acidulated aqueous liquid there may be dissolved carbohydrates, soluble alkaloidal salts, acids, organic bases and proteins. Add a small excess of NaOH solution and half its volume of an immiscible solvent and again shake, thus further separating the above into (a) and (b). (a) The alkalin aqueous extract may contain : Carbohydrates, as dextrin, sugars, gums. Soluble alcohols, as methyl, ethyl, propenyl. Soluble acids, as acetic, tartaric, citric, lactic, malic, oxalic. Alkaloids and organic bases, as urea, curarine, cinchonine, pyridine and morphine. Coloring matters, as indigo, cochineal, cudbear. Proteids, as albumin, casein, gelatin. 36 560 PHARMACEUTIC CHEMISTRY. (b) The immiscible layer may contain: Vegetable alkaloids, as quinine, strychnine, acon- itine, atropine, nicotine. Coal-tar bases, as anilin, chrysotoluidin, pyridin and their homologues. (2) In the immiscible solvent there may be dissolved hydrocarbons, oils, acids, coloring matters, resins, phenols and glucosids. Add water containing a small excess of NaOH and shake again, thus further separating the above into (a) and (b). (a) The alkalin aqueous extract may contain: Fatty acids, as stearic, oleic, palmitic, valeric. Aromatic acids, as benzoic, salicylic, phthalic. Acid coloring matters and dyes, as picric or chrysophanic acid, aurin, saffranin, alizarin or bilirubin. Acid resins, as colophony (common pitches). Phenols, as phenic and cresylic acids, thymol and creasote. Glucosids, as santonin, picrotoxin. Q)) The immiscible layer may contain: Hydrocarbons, solid, as paraffin, naphthalene, anthracene. Hydrocarbons, liquid, as petroleum products, rosin-oil, benzene. Essential oils, as turpentine, tcrpcnc and oxy- genated oils. Nitro-compounds, as nitrobenzene. Chloroform, also ethers, as ethyl oxid, ^:{\^\\ acetate, nitroglycerin, etc. Fixed fats, oils and waxes. QUALITATIVE TESTS. 56 I Neutral resins and coloring matters. Camphors, as laurel camphor, borneol, menthol. Insoluble alcohols, as amyl, cetyl and cholesterin. Glucosids, as saponin, santonin and digitalin. Weak alkaloids, as caffeine, narcotine, piperine, colchicine. THE ANALYSIS OF ORGANIC COMPOUNDS. THE QUALITATIVE TESTS. TESTS FOR CARBON.— (i) Any organic sub- stance chars; if it chars, it is organic. A few inorganic compounds, like Cu(C2H302)2, also char, while some organic substances, as CHCI3, volatilize without first charring. (2) Mix an organic substance with finely powdered CuO, heat and convey the gas into lime-water, CaCOg will be deposited in presence of organic compounds. TEST FOR HYDROGEN.— Heat the dry substance in a dry test-tube; if moisture or drops of H2O collect in the upper portion of the tube, hydrogen is present. Or, heat the substance with CuO, when water will jorm. Quantitatively, Hj may be estimated by passing the gas formed through CaClj tube previously weighed. H2 being ^ of the HjO found. TEST FOR NITROGEN.— (i) When organic sub- stance i heated with soda lime, which is a mixture of equal parts of CaO and NaOH (heated together until perfectly dry), ammonia (NH3) is formed. Heat, hold a piece of turmeric paper over the mouth of the 562 PHARMACEUTIC CHEMISTRY. tube, and a brown spot will form. This test is not universal. RELIABLE TEST FOR NITROGEN.— (2) A piece of metallc sodium (half a pea size) is placed in a long, narrow test-tube with some of the substance to be tested. Heat slowly, and carefully, until redness is reached. Protect the eyes. The C and the N will unite with the Na to form Na(CN). Break the tube in water, heat the water to extract the cyanid, filter from carbonaceous mat- ter, and add FeS04 to the solution, then HCl to acidify, and heat. The alkalin Na(CN) -l-FeSO,= Fe(OH)2 which is precipitated, and sodium ferro- cyanid formed; thus: 6Na(CN) + Fe(0H)2 - Na,Fe(CN)6 + 2NaOH and on addition of FeCl, = ferric ferrocyanid or Prussian blue is formed. (Use dry acetamid or quinolin for this test.) TEST FOR HALOGENS.— (I) The simplest test is to heat a copper wire until it ceases to color the llame green. A small quantity of an organic halogen compound is now heated on the end of the wire in the flame, which in the presence of halogen com- pounds will produce or acquire a green coloration. (Use CHI3 for a solid halid and CHCI3 for a liquid). This test sometimes jails. (2) Test for halogens in the presence oj S or N. — Acidify the solution with dilute HjSO^, boil for 5 minutes in open vessel to expel the HjS formed and the HCN. Filter, acidifv with dilute HNO,; to i cr. ULTIMATE ANALYSIS. 563 of the solution add a few drops AgNo3 solutitm. If a precipitate forms, acidify a larger portion with HCl, add a few drops of CSj and then CI2 water drop by drop, continuing the addition if / is present, until the violet color disappears. (3) Tests for Halogens in Absence oj N or S. — This is the same 'as above; omit the treatment with H2SO4 and the boiling for 5 minutes. TESTS FOR PHOSPHORUS AND SULFUR IN ORGANIC COMPOUNDS.— Sulfur and phosphorus may be detected and estimated by heating the sub- stance with nitric acid. This is done in a sealed tube provided with a capillary tube; and it should be r membered that great care is necessary in break- ing the capillary tube open. By the heating, the sulfur will be oxidized entirely to HjSO^ and the phosphorus to H3PO4. These can be tested for by appropriate reagents qualitatively or estimated quan- titatively by the usual methods. ELEMENTARY ORGANIC ANALYSIS. In the discussion under this head we will present, in outline only, principles of chemical analysis, by means of which we may determine the percentage composition and the empiric formulas of com- pounds containing carbon, hydrogen, oxygen and nitrogen, and al o suljiir and phosphorus. CARBON AND HYDROGEN.— These elements are determined by burning the body, at a red heat, in a "combustion tube" of glass, porcelain or platinum, with oxygen. Under such circumstances, the carbon 564 I'HARMACEUTIC CHEMISTRY. of the compound is hurncd to carbon dioxid, CO,; and the hydrogen i^ burned to steam, H,^. The gas- eous products, COjand H2O, are aspirated through a weighed tube containing d y calcium chlorid, CaClz- TheH20 is abso bed by the CaCl^and the increase in weight of the tube is the weight of water absorbed. The CO2 is further aspirated through a weighed tube filled with grains of a mechanical mixture of sodium hydroxid (NaOH) with lime (CaO). The COj is absorbed in this tube, forming sodium carbonate, NajCOj; and the increase in weight of the "soda lime" tube, is the weight of CO2 absorbed. Having determined its weight, we are now in a position to calculate the percentages of carbon and hydrogen in the body under examination. We must first calcu- late the weights of carbon and hydrogen from the observed weights of CO2 and HjO; thus: CO2 : C = 44 : 12. 44 : 12 = observed weight of COj : required weight of C. 18 : 2 = oljserved weight of HjO : required veight of H,. Now calculate percentages, thus: Weight of carbon determined ^ ^^^ ^ ^^^^ ^f ^^^,^^„ Weight of body taken ;„ jj^p ^^^^y Weight of hyd rogenjietermuied y^ ^^^ ^ per cent, of hvdro- Weight of body taken g^^ j^ ^Yie body." DETERMINATION OF NITROGEN. 565 NITROGEN.— This element is most conveniently determined by the method of Kjeldahl. The princi- ples concerned are as follows : I. The nitrogenous body is vigorously boiled in concentrated sulfuric acid (H2SOJ. This treatment so operates as to bring about the formation of am- monium sulfate (NH4)2S04, which salt contains all of the original nitrogen of the body under examination. II. Solution I is made strongly alkalin with sodium hydroxid (NaOH) and then boiled. The ammonium sulfate is decomposed by this process with the formation of sodium sulfate, NajSO^, and the liberation of ammonia gas (NH3): (NH,)2SO, + 2NaOH= 2NH3 + 2H20 + Na2SO,. III. The NH3 liberated from solution II is con- ducted into, and absorbed by, a solution that contains a known weight of hydrochloric acid, HCl, the HCl being in excess: NH3 + HCl = NH.Cl. A portion of the HCl is thus neutralized by the NH3. IV. Solution III is titred with a standard solution of NaOH, using phenol-phthalein or another efficient indicator. The excess of HCl is thus dete mined, from which the quantity of HCl required to neutralize the Nftg is obtained by subtraction. V. Calculate the HCl equivalent to nitrogen (in ammonia), thus: HCl : N = 36.5 : 14. 36.5 : 14 = weight of HCl used to neutralize the 566 PHARMACEUTIC CHEMISTRY. VI. Calculate the percentage of nitrogen; thus: Weight of nitr ogen determined ^ ^^^^ ,,„t ^f nitrogen Weight of body taken ^ ^he body. VOLUMETRIC ANALYSIS.— We have used the terms litre and standard solution in explaining Kjeldahl's method for the determination of nitrogen in organc bodies. It is necessary that the meaning of these terms should be explained. The principle upon which volumetric analyses are based is this: By means of the balance we prepare a solution, one unit volume of which (usually i c.c.) is made to contain a certain weight of some chemically active substance — the exact substance used being dependent upon the particular analysis we desire to make. Such a known solution, is called a standard or volumetric solution. A standard or volumetric solution of anv chemic- ally active substance is called a normal ~ solu- tion when it contains in one liter (looo c.c.) as much of the chemically active substance as is equivalent to one gram of hydrogen. If, now, in the course of an analysis, we prepare another solution that contains an unknown weight of some body that can enter into a definite chemical reaction with the body in the standard solution, the standard solution furnishes us with means for determining the actual weight of active material in the unknown solution. It is only necessary for us to measure the number of unit volumes of the standard DETERMINATION OF NITROGEN. 567 solution required to conclude a certain reaction with all of the active material in the unknown solution. Then, since each unit volume of the standard solution corresponds or is equivalent to a definite weight of the active body in the unknown solution, it is simply necessary to multiply the number of unit volumes of standard solution used by the previously determined factor which expresses the weight of active material in the unknown solution equivalent to one unit volume of the known or standard solution. We are, therefore, required to have some means both for measuring the volume of standard solution used and for determining when the reaction has been fully completed. In order to measure the volume of standard solution employed, we make use of a nar- row, graduated glass cylinder, called a burette. In order to tell the end point of our titration, we make use of a solution of some body that is capable of causing a marked color change with a minute quantity of our standard solution, but cannot do so as long as any of the active material in the unknown solution remains unacted upon. Such a body is termed an indicator, because it indicates the completion of the principal reaction. Passing from the above general exposition of the nature of volumetric analyses and coming to the Kjeldahl method for the determination of nitrogen, we have to consider the quantitative relations of the reaction between NH3 and HCI. The reaction is written : NH3 + HCI = NH.Cl. 568 PHARMACEUTIC CHEMISTRY. Therefore, 14 parts of nitrogen coriespond to 36.5 parts of hydrochloric acid. In the course of our analyses we obtained a solu- tion that contained all of our nitrogen as ammonia. This would be our unknown solution — for, while we know that it contains all of our nitrogen as am- monia, we do not know the weight present. Let us now have prepared two standard solutions — one containing 3.65 grams of HCl per litre (= .00365 grams per c.c.) ; and the other containing 4 grams of NaOH per liter ( = .004 grams per c.c.) Any given volume of either of these solutions would be exactly equivalent to the same volume of the other, thus: NaOH + HCl = NaCl + H^O. 40 36-5 Suppose that the body being analyzed weighed 5 grams and that its nitrogen after being changed to ammonia was distilled into 50 c.c. of our standard HCl. Some of the HCl would have been changed to neutral NH^Cl. Now add a few drops of an alcoholic solution of phenolphthalein (which is colorless in the presence of free HCl, but is crimson in the presence of free NaOH) ; and then run into the solution from a burette NaOH solution until a red color appears. Suppose that 30 c.c. NaOH solution accomplished this result. ELvidently 50 — 30 = 20 c.c. of our HCl was neutralized by the unknown weight of NH.,. But as i c.c. HCl wc know to be equiva- lent to .0014 gram of nitrogen. Therefore, if our 5 grams of sam])le contained .0014 X 20 = .028 gram DETERMINATION OF SULFUR AND PHOSPHORUS. 569 of nitrogen. The percentage of nitrogen is therefore 0.028., „/cO/ X 100 = .56%. Note. — By means of special volumetric analyses we determine, clinically, the quantitative composition of urines, gastric juice, water, and drug strength, etc. DETERMINATION OF SULFUR AND PHOSPHORUS. In order to determine the percentage of sulfur and phosphorus in organic bodies, we heat the bodies with strong nitric acid. By this treatment the sulphur is converted to sulfuric acid and the phosphorus to ortho- phosphoric acid. These are precipitated separately (the sulfuric acid by barium chlorid in the presence of hydrochloric acid; and the phosphoric acid by magnesium chlorid in the presence of ammonium hydroxid) and weighed, after ignition in a plati- num crucible, as barium sulfate (BaSO^), and magnesium pyrophosphate (Mg2P207), respectively. The weight of BaSO^ and MgjPzO^ are calculated to S and Pj, respectively; and thence the percentage of sulfur and phosphorus in the organic body obtained. Determination of Oxygen. — Oxygen, being difhcult to determine directly, is usually determined by difference. We determine all the other elements in the body, and subtract the sum of the percentages from 100. The remainder is taken as being the percentage of oxygen. Calculating Empiric Formulas. Having obtained the percentages of the various 570 PHARMACEUTIC CHEMISTRY. elements that enter into the composition of tlie organic body under examination, we are in a position to calculate its empiric formula. By the empiric formula for a jjody we mean the simplest formula that shows a composition in har- mony with our elementary analysis. The method for calculating empirical formulas will be understood from an inspection of the sub- joined example. An elementary analysis of lactic acid showed that it has the following elementary composition: Carbon = 40.00 per cent. Hydrogen = 6.6 per cent. Oxygen = 53.4 per cent, in 100.00 parts. Divide the above numbers by the respective atomic weights: ^=3.3 ^^=6.6 -5^=3.3 C, H., O. The ratio, therefore, is = S-3 • ^-^ • 3-3 = or =1:2:1 The carbon and oxygen atoms are, therefore, equally numerous in lactic acid, but the hydrogen atoms are twice as numerous as eitber the carbon atoms or the oxygen atoms. The simplest formula for lactic acid is, therefore, CH^O. UNSATISFACTORY NATURE OF EMPIRIC FORMULAS. We have seen above that the formula CHjO ex- presses an elementary composition in entire acco:d- DETERMINATION OF MOLECULAR WEIGHT. 57 1 ance with our analytical knowledge concerning lactic acid. But that this formula is quite irrational is evidenced by the fact that we know a number of bodies that have properties widely differing from the properties of lactic acid; but to which we would give an identical empiric formula. Such bodies are formalde- hyd, formose, grape-sugar, fruit-sugar, acetic acid, etc. A rational formula for lactic acid would show the manner in which lactic acid differs from the other bodies mentioned. Now the formula for lactic acid may very well be some multiple of CH2O. We must, therefore, write (CH20)nas theformulafor lactic acid. The "n" meaning some definite whole number as yet undetermined. We are, therefore, at this stage entirely unacquainted with the true molecular weight of lactic acid, and have no means for explaining why its properties should be expected to differ from those of certain other bodies having an identical per- centage composition. DETERMINATION OF TRUE MOLECULAR WEIGHT. We have a number of methods by means of which we may arrive at conclusions as to the molecular weights of bodies. Two of these methods we will now discuss. Molecular Weight by Chemical Reasonings. — Let us consider the well-known compound, water, seeking to discover how many times heavier is its molecule than an atom of hydrogen. 572 PHARMACEUTIC CHEMISTRY. From our analyses of water, we know it to be com- posed of hydrogen, one part, and oxygen, eight parts, by weight. Each molecule of water, therefore, con- tains at least one atom of hydrogen and one atom of oxygen. We might for the moment write the formula HO (which would make oxygen have an atomic weight of 8). Now, 23 parts of the element sodium can react with 18 parts of water, liberating i part of hydrogen; and forming a perfectly definite compound that contains all of the sodium that was used, all of the oxygen from the water, and one-half of the hydrogen from the water. It is a primary conception that an atom cannot be divided; and, since we have observed that the hydrogen in the water molecule can be split into two equal parts, it is an unavoidable conclusion that the molecule of water must contain at least two atoms of hydrogen. We are consequently in a position to write the formula H2O for the molecule of water. No experiment has ever shown that the hydrogen in the water molecule can be divided into more than two parts. Also, no one has ever been able to divide the oxygen in the water molecule. We have, then, most excellent reasons for writing the formula H^O as truly expressing the molecule of water. But the atom of hydrogen is taken as unity; the hydrogen in the water molecule, therefore, weighs two, and, since we know by analysis that water has eight times as much oxygen as hydrogen, it follows that the oxvgen in the water molecule must weigh (2X8 = 16) sixteen. The molecular weight of water is, therefore DETERMINATION OF MOLECULAR WEIGHT. 573 (2 + 16 = 18), eighteen; or, in other words, the molecule of water weighs eighteen times as much as one atom of hydrogen. By similar reasonings we could come to the con- clusion that the molecule of hydrochloric acid con- tains one atom of hydrogen. We know by analysis that one part by weight of hydrogen in hydrochloric acid can be displaced by 107.7 parts by weight of silver, with the production of silver chlorid. There- fore, 107.7 parts by weight of silver (which has been set as the atomic weight of silver) is equivalent to one acid hydrogen atom. It is quite easy for us to prepare silver lactate and to analyze the salt. We find that the same weight of silver (107.7) as is equivalent to one molecule of hydrochloric acid (36.5) is also equivalent to 90 parts of lactic acid. Lactic acid, therefore, contains one acid hydrogen atom and has a molecular weight of 90. The formula CHjO, however, gives us a molecular weight (i 2 + 2-1- 16 = 30) of 30. We must, there- fore (30 X 3 = 90), triple our formula CHjO, and write the formula for lactic acid (CH20)3.' We have thus found our previously unknown "n" to be 3. We know, nevertheless, that the body trioxymethy- lene has the formula (CH20)3 (i.e., it is identical with lactic acid in elementary composition and molecular weight) ; and we are, consequently, still without means for saying why we should expect the two bodies to be so very dififerent in their properties as we know them to be. When we come to studv the structures of the 574 PHARMACEUTIC CHEMISTRY. respective molecules, we will be furnished with our desired explanation. We will now consider another example : Ethane is a well-known gas. Analysis shows it to have the following composition: Carbon = 4 parts (80%). Hydrogen = 1 part (20%). Calculate the empiric formula: 12 3 I The hydrogen atoms are thus three times aS numerous as the carbon atoms in the molecule of ethane. We thus arrive at :he empiric formula: (CH3),. But we fmd that ^ of the hydrogen in the ethane molecule may be replaced by chlorin, with the pro- duction of the definite body, ethyl chlorid. The ethane molecule mlist, therefore, contain at least six hydrogen atoms and the formula must be CoH^; i.e., "n" here is equal to two. Molecular Weight by Avogadro's Laic. — The famous law of the Italian physicist, Avogadro, may be stated thus: "Equal volumes of all gases, at the same temperature and pressure, contain equal numbers of molecules." It, obviously, follows at once, from this law, that the relative weights of the molecules of the various gases are proportional to the relative densi- ties of the gases. It is, therefore, in fixing molecular weights by the application of Avogadro's law, first necessary to fix DETERMINATION OF MOLECULAR WEIGHT. 575 the molecular weight of hydrogen (the hydrogen atom being the unit of mass) ; and then to determine the densities of other gases relative to the density of hydrogen. The hydrogen molecule is known to contain at least two atoms of hydrogen; and is not known to contain more than two atoms. The molecule of hydrogen, therefore, weighs two. The density of hydrogen is taken as one. The molecular weight of hydrogen being, thus, twice its density, it follows that the molecular weight of any gas is twice its density (compared with hydrogen). So, in order to set the molecular weight of any body by the law of Avogadro, we determine how many times heavier is any volume of the body in the gaseous state than the same volume of hydrogen. The density figure being determined, it is multiplied by two; and the product is the molecular weigh't of the body (in its gaseous state) . This method for determining molecular weights is far simpler and much more direct than the chemical method; but it is only applicable to gases and to such liquids and solids as can be vaporized without de- composition. The molecular weight of a body as set by purely chemical methods is always identical with the molecular weight determined by the application of Avogadro's law. 37 576 PHARMACEUTIC CHEMISTRY. Examples: Gas / Density (Hydrogen = i) Molecular weight Density X 2 Steam Hydrochloric acid. . Ethane 9- i8.2S 15- 32.25 etc. 18. 36.5 30- 64.5 etc. Ethyl rhlorid etc. The two methods of vapor density determination prominently mentioned are: {a) THE CRYOSCOPIC METHOD.— Depending upon the depression produced in the freezing-point of a solvent by a known weight of the substance. This was the original method and known as the "freezing-point method" or "Beckmann method." {b) THE VICTOR MEYER METHOD.— Depend- ent, as stated before, on the comparison of the vapor density with a standard (hydrogen). The substance is converted into a vapor, which displaces air. This vapor is caught in a graduated tube of the apparatus. The collected volume of gas is corrected for tempera- ture and pressure to o° and 760 mm. of mercury. The weight of this corrected volume is compared with the weight of the same volume of hydrogen (stand- ard). To illustrate: 0.073 g"^- ^^ ether displaced 25.3 c.c. of air. The column of displaced air was read at 21.5° and 718.6 mm. pressure. What was the volume of the ether vai)t)r? ^5-3 X 273- 73- + 21.5- 23.46 QX. of vapor. TOXICOLOGY. 577 This corrected for pressure: 718.6 less 19. 1 (vapor tension of HjO at 21.5°) = 699.5 iTim. Then — 23.46 c.cX ^^'^ =21.5 c.c. of ether vapor — at 0° C. and 760 mm. pressure. This volume of hydrogen weighs, — ^^ — l_v = 1. 000 0.00197 gram of H2. The quantity of ether originally taken divided by the equi\alent weight of hydrogen, '^'■^ =37-6 specific gravity of the ether vapor. TOXICOLOGY. Toxicology is a branch of medical science which treats of poisons. In this short article are included the definitions, effects on the living body, symptoms and treatment within the body. Also an abstract of the Pennsylvania poison law. True poison may be defined as a substance which when absorbed by the system produces great physical injury or death. Exami)les: hydrocyanic acid, mor- phine, strychnine. A corrosive poison is a substance which destroys the tissues with which it comes in contact. Examples : the acids, like sulfuric and nitric. These two main classes of poisons should be distinguished; thus: Sulfuric acid, which is a cor- rosive, burns the tissues with which it comes in con- tact; strychnine, which is a true poison, on the other 578 PHARMACEUTIC CHEMISTRY. hand, will do no injury lo the tissues, but when ab- sorbed into the blood it will produce death. Sulfuric acid, largely diluted, loses its corrosive properties; strychnine is no less poisonous whatever the dilution. Some poisons, like corrosive sublimate and arsenic, possess the properties of both true and corrosive poisons, and are called irritant poisons. The State Pharmaceutical Examining Board in their instruc- tions to the pharmacists regard as a poison, any drug, chemical or preparation which, according to standard works on medicine or materia medica, is liable to be destructive to adult human lije in quantities oj sixty grains or less. Substances which produce deleterious effects or cause death due solely to mechanic action are not poisons. The taking into the system of such substances as crushed glass, metal filings, boiling water, etc., may produce injury or death due solely to mechanic action. A cumulative poison is one that slowly collects in the system when taken jor some time. Such arc digitalis, mercury, lead, iodin, etc. Poisons may be administered with some other criminal intent than that of murder; the criminal administration of abortifacients and the use of narcotics in attempted rob])eries, etc., being well- known examples. The effects of poisons arc both local and remote. 'The jornier being the direct impression on the tissue with which the poison may come in contact {e.g., the corrosive effect of the mineral acids on the skin or ANTIDOTES. 579 mucous membrane). The latter are those resulting from the action oj the poison upon the blood, brain or spinal cord after having gained entrance into the system (e.g., the tetanic effect of a large dose of strychnine on the spinal cord after being absorbed from the stomach). Some poisons act both locally and remotely (e.g., arsenic acts locally on the stomach and remotely on the brain) . The usual symptoms of poisoning are due to the remote effects and are of value in the diagnosis of a case. Various conditions which affect the toxic action of poisons: (i) Dose; (2) age; (3) habit; (4) idiosyn- crasy; (5) state of health; (6) the condition in which the poison is administered; (7) the mode of intro- duction into the system; (8) the amount of food in the stomach at the time the poison is administered or taken; (9) combination of poisons. Poisoning may be acute, when produced by taking one large dose of poison ; chronic, when produced by long continued absorption of minute quantities of the poison; thus: mercurialism, produced by long- continued dosing with mercury salts; saturnism, pro- duced in painters and plumbers working with lead (lead-poisoning); iodism, cinchonism, etc., are all forms of chronic poisoning. AN ANTIDOTE is any measure or agent, which counteracts the effects of a poison or an attack of disease. Antidotes are divided into mechanic, chemic and physiologic. Examples of MECHANIC ANTIDOTES may be had in the stomach-pump, demulcents, as flour paste, 580 PHARMACEUTIC CHEMISTRY. mucilages, fixed oils and egg albumen. This last agent serves also as a chemical antidote for copper and mercury, forming albuminates (excess should be avoided in mercury poisoning as it forms a soluble double albuminate). CHEMIC ANTIDOTE is one which combines with the poison, forming harmless or insoluble compounds; thus, magnesium oxid with the corrosive acids forms harmless sulfate, chlorid or nitrate, etc.; common salt precipitates lunar caustic and other silver salts forming insoluble silver chlorid. A PHYSIOLOGIC ANTIDOTE, also called "an- tagonist," is one which produces opposite — antago- nistic — effects in the system; thus, physostigma is antagonistic to strychnine ; digitalis antagonizes aco- nite; atropine a-nidigomzts morphine. The physiologic antagonists are best administered hypodermically. CONTRAINDICATION OF ANTIDOTES.— The stomach-pump should never be used in strong mineral acid or oxalic acid, strong alkali or corrosive sublimate poisoning (perforation of esophagus or stomach may result). Alkalis, should never be used in neutralizing oxalic acid (the alkalin oxalates are poisonous and more soluble) ; the alkali carbonates are contraindicated in corrosive acid poisoning (COo is given off, which is apt to rui)ture the corroded stomach and intestines). Oils should never be used in phosphorus, j^henol, creasote and cantharides poisoning (they dissolve phos])horus and canthari- din, etc.). TREATMENT OF UNKNOWN POISONING.— In SYMPTOMS OF POISONING. 58 1 the case where the poison is unknown, administer JeauneVs universal antidote^ composed of solution ferric sulfate, 75 c.c; magnesium oxid, 60 gm.; animal charcoal, 30 gm.; water, 600 c.c; give in 2 wineglassful doses every 3 minutes. This is also known as the ^^ mulHple antidote," and acts as fol- lows: The magnesia neutralizes any acid present, the iron salt combines with any arsenical poison, and the charcoal absorbs or precipitates any alkaloid. This treatment should, if necessary, be followed with stimulants until the physician arrives. The STIMULANTS generally used in poisoning cases are: brandy, whisky, alcohol, ether, tincture of capsicum per rectum, strong tea or coffee. Strong coffee, preceded by emetic and a little tannin, is a reliable antidote for the narcotic (solanaceae) poisons. SPECIAL SYMPTOMS SUGGESTING CERTAIN COMMON POISONS. Organic. (i) Aconite: numbness, tinghng and paralysis. (2) Alcohol (acute): unconsciousness, dilated pu- pils, cold skin. (3) Belladonna, atropine: active delirium, dilated pupils, hot skin, etc. (this applies to all the solana- ceae). (4) Conium: paralysis of limbs; vertigo, convul- sions, mind clear, double vision. (5) Digitalis: heart very slow, rapid during move- ment, with nausea, pain, vertigo, disturbed vision. (6) Headache powders (phenacetin, antipyrin. 582 PHARMACEUTIC CHEMISTRY. acetanilid) : depression, vomiting, blueness of lips chilliness, collapse. (7) Nux vomica: severe convulsions and s])asms, opisthotonos, clear intellect until the end. (8) Opium and its preparations: unconscious- ness, contracted pupils, congestion. (9) Phenol (carbolic acid) : note odor or stains. (10) Ptomain or mushroom poisoning: severe vomiting and purging, chills, collapse. (11) Santonin: yellow color of urine; \cllo\v vision. Inorganic. (i) Acids and corrosive irritants: great pain, cold skin, collapse. (2) Antimony and copper: same as above; but in the latter the vomited matter is green or blue. (3) Arsenic: severe vomiting, severe burning in the mouth, esophagus (gullet) and stomach, bloody stools, convulsions, cold sweats, coma (unconscious- ness) . (4) Alkalis: severe burning in throat and stom- ach, stricture of esophagus, violent pains in stomach, cold skin, etc. (5) Corrosive sublimate: practically the same symptoms as arsenic, but appearing more rapidly. (6) Hydrocyanic acid and cyanids: death ra])id, symptoms rarely noted. Short convulsions, odor of almond oil may be noticeable. (7) lodin, bromin: similar sym})toms to last, but not quite so severe. (8) Lead salts: burning pains in throat and stom- TREATMENT IN CASES OF POISONING. 583 ach, thirst, intense colicky pains in al:)d.omen. In chronic poisoning: severe colic (lead colic), paralysis of hands and feet (lead palsy) ; blueness of gums, obstinate constipation. (9) Mineral acids: severe burning in throat and stomach, severe vomiting of black or reddish matter, convulsions, pains in bowels. (10) Phosphorus: Abdominal pains, severe vomit- ing (having odor of garlic), jaundice, suppressed urine, delirium (vomited matter phosphorescent in the dark). (11) Silver nitrate (treatment same as antimony and copper) : hard white patches about mouth (turning black in time). GENERAL METHOD OF TREATMENT OF CASES OF POISONING. In the treatment of cases of poisoning the following general method is recommended: (i) Remove the poison from the stomach or chemically and mechanically antidote the poison. (2) Administer physiologic antidotes or adopt such measures as will antagonize the action of that portion of the poison which has been absorbed. (3) Promote the elimination of that portion of the poison which has been absorbed from the system by resorting to such means as the nature of the poison may suggest. (4) Combat any dangerous symptoms and en- deavor to keep the patient alive until the toxic effects have disappeared. 584 PHARMACEUTIC CHEMISTRY. These general methods require brief discussion: (i) Removal of the poison from the stomach may be accomplished by the induction of vomiting by the use of emetics or by tickling the fauces or by the use of the stomach-pump or stomach-tube. Emetics are classitied, according to their physio- logic action, into two kinds: Peripheral and Centric. — Peripheral emetics act locally, principally upon the terminations of vagi in the stomach or locally upon the terminations of the fifth and glossopharyngeal nerves in the mucous membrane of the fauces. Centric emeti-cs act by stimulating the vomiting center in the medulla ob- longata. Some examples of emetics: Flour of mustard, ^ to 2 tablespoonfuls in ^ glass of water. Tartar emetic, ^ to i grain (wine of antimony contains two grains of tartar emetic to each ounce). Zinc sulfate, 15 to 30 grains. Powdered ipecac, 15 to 30 grains. Ammonium carbonate, 15 to 30 grains. Copper sulfate, 5 to 10 grains. Apomorphine, yV grain hypodermically. Copious draughts of tepid water. Mustard irritates the gastric mucous membrane and is a good example of a peripheral emetic. .\pomorphine stimulates the vomiting center and is a typical centric emetic. Antimony (tartar emetic) acts in both ways: it irritates the gastric mucous membrane and also stimulates the vomiting center in the medulla. TREATMENT IN CASES OF POISONING. 585 Poisons may be removed from the stomach by means of the stomach-pump or the stomach-tube, and the stomach in the use of either may at the same time be washed out. 586 PHARMACEUTIC CHEMISTRY. POISONS AND THEIR ANTIDOTES. Poison (i) Mineral Acids. (H,S04 HNO., HCl and nitro - hydro- chloric acid.) (2) Vegetable Acids. (Oxalic acids and salts; tartaric acids and salts.) (3) Alkalis. ■ (NaOH, KOH,NH4- OH and their car- bonates.) .\ntidotcs Give no emetic. Magnesia mi.xed with water, milk, whit- ing, fixed oils, demulcents, Laudanum (20 drops) if much pain. (No stomach-pump.) Chalk, whiting, air-slacked lime with vinegar. (No soda or potash to neutralize acid.) Mustard water, olive oil, de- mulcents and stimulants. {No stomach-pump.) Warm water till emetic; vinegar, lemon juice or citric acid. Olive oil, demulcents, and Tr. opium (20 drops) if much pain. {No stomach-pump.) (4) Barium, lead and their \ Epsom {h oz.) or Glauber's salt salts. (r oz.) in water. Emetic (mustard water), milk and demulcents, and laudanum if needed. (5) Arsenic and all its compounds. (6) Antimony salts, can- tharides, colchicum, elaterium, io din, copper, mercury, croton oil, savin, tansy, potass, bi- chromate, tin and zinc salts. Emetic (mustard water), hy- droxid of iron or hydroxid of iron with magnesia, olive oil, albumen, demulcents and Tr. opium. Albumen diffused in water. Emetics (warm) water with NaHCOj or mustard), strong tea or coffee, or tannin, stimu- lants, Tr. opium (if needed) and demulcents. POISONS AND THEIR ANTIDOTES. 587 POISONS AND THEIR ANTIDOTES.— Cow/mwe^i. Poison Antidotes (7) Niix vomica and] strychnine. (8) Silver nitrate. (9) Cannabis indica, opium and morphine. (10) Aconite, digitalis, er- got, lobelia, tobacco, veratrum, bella- donna, coniu m , henbane, santonin, stramonium, cala- bar bean. (11) Phosphorus. (12) Alcohol, chloral, ether, chloroform. (13) Hydrocyanic acid and the cyanids. Emetics (mustard water), pow- dered charcoal, iodized starch or tannin. To relieve spasms inhalations of chloroform or, internally, 25 grs. chloral hy- drate or i oz. potassium bro- mid. Lose no time. Sodium chlorid, emetics (mus- tard water), demulcents. Emetics (mustard water) or stomach-pump, cold affusions, strong tea or coffee; electro- magnetism. Keep patient awake and in motion. Artifi- cial respiration. Emetics (mustard water), strong tea or coffee. Hypodermics of morphine; powdered char- coal; stimulants, (whisky), etc. Warmth to extremities and artificial respirations. Emetics (CUSO4, 3 grains every 5 min.) f3i old oil turpen- tine, Mg.SO^ (^ oz.). No oils. Emetics (mustard mixture), stomach-pump, strong coffee or tea, cold affusions, artificial respiration, mustard poultice to limbs. Mild inhalations of ammonia, cold applications to head; in- ternally, the following three solutions in order given: {a) Potassium carbonate, 1 5 grains, in H2O, if§; (6) iron sulfate, i5grainsin H2O, ifo ; (c) tincture iron chlorid, ifo. (This forms the harmless "Prussian blue.") 588 PHARMACEUTIC CHEMISTRY. ABSTRACT OF THE PENNSYLVANIA POISON LAW. Unregistered dealers may sell the commonly used drugs and medicines in packages that have been legally prepared by or under the supervision of regis- tered pharmacists. After the law in regard to the mixing or com- pounding and dispensing of drugs, medicines and medicinal preparations has been complied with, it is permissible for general storekeepers and merchants who are not registered pharmacists to sell legally prepared packages of the commonly used medicines and poisons, subject, of course, to the same restric- tions that are placed upon properly qualified and registered pharmacists in regard to purity and strength under the Act of May 25, 1897; and under the restrictions of Section 10 of the Act of 1887, which is as follows: "Section 10. — A poison, in the meaning of this Act, shall be any drug, chemical or preparation which, according to standard works on medicine or materia medica, is liable to be destructive to adult human life in quantities of sixty grains or less. No person shall sell at retail any poisons except as herein provided, without affixing to the bottle, box, vessel or package containing the same a label, printed or plainly written, containing the name of the article, the word ^^ poison " and the name and place of business of the seller; nor shall he deliver poison to any person without satisfying himself that such ]K)i.son is to be used for legitimate purposes. THE PENNSYLVANIA POISON LAW. 589 It shall be the further duty of any one selling or dispensing poisons, which are known to be destruc- tive to adult human life in quantities of five grains or less, before delivering them, to enter in a book kept for this purpose the name of the seller, the name and residence of the buyer, the name of the article, quantity sold or disposed of and the purpose for which it is said to be intended, which book of registry shall be preserved for at least two years, and shall at all times be open to the inspection of the coroner or courts of the county in which the same may be kept. The provisions of this section shall not apply to the dispensing of physicians' prescriptions specifying poisonous articles, nor to the sale to agriculturists of such articles as are commonly used by them as in- secticides. Any person failing to comply with the provisions of this section shall be deemed guilty of a misdemeanor, and upon conviction thereof shall be punished by a fine of not less than five nor more than fifty dollars for each and every offense. Wood or methyl alcohol cannot he used in the com- pounding of pharmaceutical preparations. The standards of law in this State do not permit the use of wood or methyl alcohol (this includes Columbian spirits, colonial spirits, kahol, etc.) in compounding and preparation of formulae contained in the U. S. Pharmacopoeia and National Formulary, and any one so using it will be subject to the penal- ties of the Act of May 25, 1897, and will be promptly dealt with by this Board according to law. 590 PHARMACEUTIC CHEMISTRY Penalty: Fine ($ioo), imprisonment (90 days); either or both at discretion of court. AN ACT. Regulating the sale or prescription of cocaine, or of any patent or proprietary remedy containing cocaine, and prescribing penalties for the violation thereof. Section i. Be it enacted, etc., That no person shall sell, furnish or give away any cocaine, or any patent or proprietary remedy containing cocaine, e.xcept upon the prescription of a registered practic- ing physician, or of a dentist, or of a veterinarian; nor shall any such prescription be refilled; nor shall any physician, dentist or veterinarian prescribe cocaine, or any patent or proprietary remedy con- taining cocaine, for any person known to such physician, dentist or veterinarian to be an habitual user of cocaine: Provided, That the provisions of this Act shall not apply to persons engaged in the whole- sale drug trade, regularly selling cocaine to persons engaged in the retail drug trade. Section 2. Any person violating any of the provi- sions of this act shall be sentenced to pay a fine of not more than one hundred dollars and undergo an imprisonment of not more than six months, or both, or either at the discretion of the court. Approved — The 22d day of April, A. D. 1903. INDEX Abietic anhydrid, 503 Acacia, 502 Acetaldehyd, 335 Acetaldoxirn, 380 Acetal salicylate, 326 Acetamid, 383 Acetanilid, 437, 439, 441 poisoning, 582 Acetone, 340, 341 dioxy, 395 collodion, 342 properties, 341 sodium bisulfite, 341 Acetonitril, 376, 384 Acetophenone, 478, 479 Acetoxime, 380 Acetphenetidin, 458 Acetyl benzene, 478 chlorid, 3 71 group, 372 para-amido phenyl salicyl- ate, 491 salicylic acid, 492 Acetylene series, 242 table, 243 Acids, 16, 67, 182, 212 abietic, 547 acetic, 345, 351 acetic glacial, 351 anhydrid, 372 amido, 367 amino, 384 acetyl salicylate, 492 acrylic, 299 adipic, 358 alcohol, 480 alphahydroxy-propionic, 368 amidoacetic, 367 benzoic (ortho), 486 amino acetic, 384 propionic (alpha), 385 succinic, 366 succinamic, 366 anhydrids, 372 mixed, 372 anisic, 481 anthranilic, 486 arachidic, 346, 358 38 Acids, aromatic, 481 hydroxy, 480 preparation, 482 table, 480 arsenous, 74 aspartic, 366 atropic, 480 barbituric, 392 basicity, 67 behenic, 346 benzoic, 480, 482, 483, 47; 476, 385, 429 • derivatives, 483 benzenepentacarboxylic, 480 beta cyanpropionic, 364 naphthylortho-oxymeta- toluic, 516 brombenzoic-meta, 485 ortho, 485 para, 485 butyric normal, 355 fermentation, 355 capric, 345 capryhc, 345 caproic, 345 carbamic, 361 carbazotic, 454 carbolic poisoning, 582 antidote (see Phenol) carbonic, 73, 358, 359 derivatives, 361 camaubic, 346 catechutannic, 495 cerotic, 346 chloric, 71 chlorids, 370 chlorous, 71 cinchomeronic, 530 cinchotannic, 495 cinnamic, 488, 489 citric, 300 copaibic, 505 coumaric, 481 crotonic, 244 cumic, 488 cyanacetic, 359 cyanic, 378 cyanuric, 378 591 592 I Acids, cynamic, 480 daturic, 346 derivatives of, 370 dextrq-tartaric, 301 dialuric, 392 diazo-benzene sulfonic, 428 dibasic, 72 organic, 358, 359 dichlor-acetic, 370 digallic, 494 dihydroxybarbituric, 392 dithiocarbonic, 381 ellagic, 493 ethylsulfonic, 373 formic, 34S. 349 fulminic, 377 gallic, 381, 493. 494 gallo, tannic, 494 glutaric, 358 glycerophosphoric, 322 glycoUic, 367, 368, 399 guaiacic, 504 guaretic, 504 gummic, 502 halids, 212 hippuric, 384 hydriodic, 38 hydrochloric, 70 hydrocyanic, 69 poisoning, 582 antidote, 587 hydrocynamic, 480 hydrofluoric, 33 hydrosulfuric, 72 hydroxy, 348, 489 hydroxypropionic, 367 hydroxysuccinic, 366 hyenic, 346 hypochlorous, 71 hypophosphorous, 70 hyposulfuric, 72 isoacetic, 346 isobutyl acetic, 345 isobutyric, 345, 356 isonicotinic, 529 isophthalic, 432 isosuccinic, 365 isothiocyanic, 379 isovaleric, 345. 3S6, 357 kramerotannic, 495 lactic, 368 varieties, 369 laevo-tartaric, 301 lauric, 345, 358 lignoceric, 346 malic, 365, 366 malonic, 358, 359, 364 mandelic, 481 mastichic, 504 mellilotic, 481 mellissic, 346 Acids, mellitic, 480 mesetylenic, 480 meso-tartaric, 301 meta-oxy-benzoic, 480 metaphosphoric. 70 melhyl-ethyl-acetic, 345, 357 mineral poisoning, 583 antidote, 586 monochlor-acetic, 370 myristic, 345, 358 naphthalene sulfonic, 517, 518 naphthalic, 518 naphthionic, 518 naphthoic, 518 nicotinic, 529 nitric, 69 nitrobenzoic (ortho), 485 (meta), 48s (para), 486 nitrohydrochloric, 71 nitrous, 68 nomenclature, 68 cenanthylic, 345 oleic, 244 organic antidotes, 586 organic basicity, 347 nomenclature, 368 occurrence, 349 preparation, 349 properties, 348 orsellinic, 481 orthohydroxy-benzoic, 489 orthophosphoric, 74 oxalic, 358, 359. Sf^i antidotes, 5S6 toxicology, 363 oxids, 183 oxy, 348, 367 oxytoluic, 481 palmitic, 346 parabanic, 391 paralactic, 369 paraoxy-benzoic, 480 pelargonic, 345 perchloric, 71 phenol, 480 I)henol-sulfuric, 452 phenyl-acetic, 480, 488 phenyl-acryllic, 488 phenyl-propiolic, 480 phenyl-propionic. 488 phthalic, 432. 480 phosphorous, 73 picolinic, 529 picric, 454 pimelic, 358 propionic, 34S. 354, 37^ protocatechuic, 481, 49 1 prussic, 30, 69 Scheele's, 30 593 Acids, pyroligneous, 351, 352 pyro-mellitic, 480 pyro-phosphoric, 75 sulfuric, 73 tartaric, 303 pyruvic, 368 quercitannic, 495 quinic, 481 quinolinic, 530 racemiff, 301 salicylic, 480, 489, 490 ^arcolactic, 369 silicic, 47 sozalic, 452 stearic, 346 substitution, 370 succinic, 358, 364 normal, 365 sulfanilic, 428 sulfo-benzoic, 486 sulfocyanic, 378 sulfocarbolic, 452 sulfuric, 702 aromatic, 703 sulfurous, 702 tannic, 494 tartaric, 301 terephthalic, 432 thiocarbonic, 381 thiocyanic, 378 thiosulfuric, 73 toluic, 432, 480 meta, 487 ortho, 487 para, 487 tribasic, 74 trichloracetic, 338 tridecylic, 345 trimethylacetic, 345, 357 trioxyacryllic, 391 trioxybutyric, 399 trithiocarbonic, 381 tropic, 481 trimesic, 480 undecylic, 345 uric, 390, 391 derivatives, 390 valeric, 345. 356, 367 vanillic, 481 vegetable antidote, 586 xanthogenic, 381 xylylic, 480 Aconite antidote, 587 poisoning, 581 Acrolein, 299 Adhesion, 3 Adjacent, 421 Affinity, chemical, 3 Airol, 494 Alabaster, 135 Alanin, 385 Alcohol, 206, 211 Alcohol, 21 1 absolute, 270 allyl, 279 amyl, 280 anisyl, 474 antidote, 587 aromatic, 450, 472 cinnamyL 473 commercial, 270 deodorization, 270 diatomic, 282 dilute, 270 diphenyl, 479 distillation, 269 ethyl, 266 grain, 266 isomeric, table of, 278 isomerism, 276 isopropyl, 277 manufacture, 269 methyl, 264 nomenclature, 276 orthohydroxybenzyl, 473 oxidation, 277 paramethoxybenzyl, 474 piperonyl, 474 poisoning, 581 polyatomic, 300 preparation of, 262 primary, 260 properties of, 263 propyl, 277 salicylic, 473 secondary, 262 synthesis of, 306 table of, 261 tertiary, 262 triatomic, 285 vanil, 474 vanillin, 474 wood, 266 Alcohols, reaction of, 332 resin, 332 salicylic, 476 structure of, 329 table of, 327 valeric, SS4, SS7 Aldehyd, 335, 211 ammonia, 331 anisic, 477 aromatic, 472, 474 benzal, 474 benzoic, 549 butyric, 554 cinnamic, 476. 549, 5SS cuminic, 478 formic, 333 glyceric, 395 glycollic 395 group, 329 hydroxy, 367, 395 lauric, 557 594 INI Aldehyd, methylene-ether of proto-catechuic, 478 methyl-protocatechuic, 477 preparation of, 328 properties of, 328 proto-catechuic, 477 Aldobiose, 395 Aldol, 336 Aldoses, 395 Aldotriose, 395 Aldoximes, 331 Aliphatic series, 214 Alizarin, 522, 523, 525 blue, 524 orange, 524 synthesis, 522 Alkali metal group, 140 poisoning, 582 antidotes, 586 Alkaloid, 531 animal, 538 cadaveric, 538 discussion of, 536 doses, 539, S40 extraction of, 537 myotic, 534 nomenclature of, 536 occurrence. 536 solubilities of, 539, 540 tests for, 538 table of, 539, 540 unofficial, 536 Alkaloidal salts, 537 Alkyl, 430 acetates, 372 aniliri, 438 halids, 213, 259 sulfonic acid, 373 chlorid, 374 Alkyl sulfonic ester, 373 AUotropism, 184 Alloxan, 392 Alloy, 185 Ally! iso-thio-cyanate, 284, 379 SS7 Allyl sulfids, 284, 382 Aloin, 497, 498 Alpha-methylhydroxylamin, 380 Alum (kinds of), 118 compounds, 119, 120 dried, 119 preparation, 118 Aluminum, 1:7 bronze, 118 preparation, 1 1 7 properties, 1 1 7 tests, 121 Amalgam, 185 Amber, 503 Amid, 383, 212 Amido azo benzene, 448 benzene, 43s Amido compounds, 447 Amid phenol, 458 propion, 383 Amin, 212 dimethyl, 541 diphenol, 438, 440 propyl, 541 triethyl, 541 Amins, aromatic, 435 varieties, 43? preparations, 386 primary, 386 secondary, 386, 388 tertiary, 386, 388 tri phenyl, 438 Amino acid, 384 azo^benzene, 446 Ammonia, 25 tests, i6s Ammoniac, 511 Ammonium, 161 carbonate, 362 compounds, 162 cyanate, 316, 203 ichthyosulfonate, 4S3 molybdate, 175 picrate. 454 propionate, 376 sulfid group, 108 sulfo cyanid, 314 thio cyanate, 378 Amorphous, 184 Amygdalin. 475, 497 Amylacetate, 281, 326 Amylene, 238 hydrate, 281 Amyl methyl ketone, ss4 nitrite, 281 Amylopsin, 267 Analysis, elementary, 563 organic, 561 volumetric, 566 Anethol, 554, 55 5 Anhydrid, 183, 213 abietitj, 503 acetic, 373 propionic, 312 succinic, 365 Anhydro gluco chloral, 339 Anilin, 408, 435, 436 alkyl, 438 derivatives, 438 dimethyl, 43O, 440 dyes, 440 hydrochlorid, 430 methyl, 438, 439 nitrate, 436 salt. 436 sulfate, 436 Anions, 179 Anisol, 452, 477 Anode, 178 595 Antagonists, 580 Anthracene, 408, 520 substitution products, 521 synthesis, 520 Anthracite, 28 Anthra quinon, 521 beta sulfonic acid, 522 Antidotes, 597 chemic, 580 contraindications, 580 Jeaunel's universal, 581 mechanic, 579 multiple, 581 narcotic poison, 581 physiologic, 580 table of, 586, 587 Antimony, 94 compounds, 95 poisoning, 582 antidote, 586 potassium tartrate, 95 preparations, 94 properties, 94 tests, 96 Antipyrin, 535 poisoning, 5S1 Antitoxins, 542 Apple oil, 323 Arabitol, 306 Arachin, 297 Arbutin, 497, 501 Argols, 144. 302 Armstrong's nucleus, 415 Aromatic hydrocarbons, 407 diketones, 479 Arsenic, 89 antidote, 586 compounds, 90 iodid, 91 poisoning, 582 preparations, 90 properties, 90 solution (Fowler's), 91 sulfid, 91 tests, 93 toxicology, 93 wall paper, 92 white, 91 Arsin, 388 tertiary, 389 Arsonium, 388 Aryl, 430 Asafetida, 509 Aseptol, 452 Asparagin, 366 Asphalt, 503 Aspirin, 492 Asymmeteric, 369, 421 Atmosphere, 61 composition, 61, 62 impurities, 63, 66 Atomic weights, 11 Atomicity, 13 Atropine, S3i antidote, 587 poisoning, 581 Aubepine, 477 Aurin, 463 Australene, 544. 557 Autointoxication, 541 Azo benzene, 446 compounds, 445 Baker's ammonia, 162 Baking powder, 305 Baking soda, 153 Balata, 548 Balsams, 507 Balsamic resins, 503 Balsam of fir, 506 of peru, 508 of styrax, 509 of tolu, 508 Bamberger's formula, 513 Barium compounds, 133 oxids, 133 salts, antidote for, 586 tests, 133 toxicology, 133 Bases, 15, 182 Basic organic compounds, 408 Battery ammonia, 162 Bayer's benzene ring, 415 Beckman method, 576 Bdelium, 510 Beef tallow, 294 Beer manufacture, 271 Benzal chlorid, 430. 435. 475 Benzaldehyd, 475. 445 Benzaldehyd phenyl hydrazone, 445 Benzamid, Benzene, 408, 417a, 441 addition compounds of, 413 amyl, 417b butyl, 417b constitution of, 413 derivatives of, 418 diazoamido, 448 diazohydroxy, 449 diazo nitrate, 448 dichlorid, 413 dimethyl ethyl, 417b dinitro, 426, 427 disubstituted, 421 identification of, 422 halogen derivatives of, 425 hexabrom, 413 hexabromid, 425 hexachlor, 413, 425, 426 hexahydrid, 413 homologues, synthesis of, 424 hydrocarbons, table of , 4 1 7a 596 Benzene, hydroxy, 449 isopropyl, 417a metadibrom, 422 methyl, 424 methyl amido, 416 monochlor, 425 mono substituted, 419 nitro, 419 nitrobrom, 418 nitro derivatives of, 426 ortho dibrom, 422 para dibrom, 422 para sulfonic acid, 428 para methyl propyl, 433 penta, 422 penta methyl, 417b properties of, 413 propyl normal, 417a ring, Bayer's, 415 ring, Kekule's, 413 series, 407 substitution of, 413 sulfonic acid, 427, 428 sulfo derivatives of, 427 synthesis of, 412 tetra, 422 tetra methyl, 417b tribrom, 423 tribromid, 413 trichlor, 426 triethyl, 417b tri-iodo, 413 tri methyl, 417a tri substituted, 421, 423. 424 Benzidine, 446 dyes, 446 Benzenyl chlorid, 430 Benzoic anhydrid, 484 Benzoin, 508 Benzol, 408, 411 Benzonitril, 48s Benzophenone, 479 Benzoquinon, 479 sulfinid, ,486 Benzoyl chlorid, 484 Benzoyl group, 484 Benzoyl glycin, 384 Benzyl alcohol, 434. 472, 4", 476 Benzylamin, 440 Benzyl benzoate, 484 chlorid, 430. 434. 472 Benzyledene chlorid, 430 Belladonna poisoning, 581 antidote for, 587 Beryllium, 176 Betain, 38s Beta methyl hydroxylamm, 3S Beta naphthol, 576 Betol, 492 Beverages, 269 aichlorid -mercury, poisoninK by. 582 Biebrich scarlet, 407 Bismuth, 98 beta-naphthol, 516 Bismuth compounds, 99. loi gallo-oxy iodid, 494 preparations, 98 properties, 98 Bismuth subgallate, 493 tests for, loi Bisulfite compounds, 330 Bittern, 36 Bituminous coal, 28 Blasting gelatin, 404 Blue anilin, 46s methylene, 465 Paris, 313 Prussian, 313 Williamson's, 313 Bonds, T3 acetylenic, 210 olefinic, 210 paraffinic, 210 Boquet, 322 Borax, 154 Bomeol. 548, S49. SS2 5S7 esters, 548 Bornyl acetate, 548 Boron, 45 Bromal, 339 Brandy, 274 Brom benzene, 444 Bromelin, 267 Bromin, 35 Bromin compounds, 37 poisoning, 582 antidote (see Cyanid) preparation, 36 properties, 36 Bromoform, 253 Brucine, 534 Burette, 567 Burgundy pitch, 506 Butane, 229 Butter, 294 substitutes, 29s Butterine, 29s Butyl chloral, 339 hydrate, 339 Butyline, 238 Butyrin, 294 Butyrone, 340 Cacao butter, 296 oil, 297 Cacodyl, 389 Cadet's liquid, 389 Cadinene, 544. 546, SS4. 555. SS7 Cadmium, 104 compounds, 105 597 Cadmium, description of, 105 Caffein, 393, 534 citrated, 534 Calabar bean, antidote for. Calcium, 135 acetate, 341 benzoate, 475 carbid. 138 compounds, 13s formate, 475 oxylate, 364 phosphate, 138 preparations, 135 properties, 13s tests, X39 Calcutta niter, 143 Calico, 470 Calx, 136 Camphene, S47. SS2, SS7 Camphor, 549, 557 artificial, S4S mono bromated, 551 Canada balsam, 506 Cannabis indica, 587 Cannel coal, 28 Candles, manufacture of, 296 Cantharides, antidote for, 586 Caoutchouc, 512 Caprone, 340 Caramel, 400 Carbamid, 203, 360, 362 Carbamin, 376, 439 Carbazole, 520, 530, 531 Carbhydrates, 212, 394 Carbocyclic series, 407 Carbohydrate, 394 Carbon, 26, 207 amorphous, 28 asymmetric, 369 disulfid, 208, 557 determination of, 563 forms of, 207 oxids of, 29 oxychlorid, 359 source of, 208 tetra chlorid, 253 tetra iodid, 255 valence of, 211 Carbonate group, 132 Carbonyl, 208 Carbonyl chlorid, 359 Carboxyl group, 347 Carmalite, 142 Carvacrol, 457, 549 Carvene, 545 Carvone, 549. SS4> SS6 Caryophyllene, 554, 555 Catalase, 267 Catalytics, 22 Catechol, 460 Cathion, 179 Cathode, 178 Celestite, 133 Cellulose, 394, 403 Cement, 120 hydraulic, 121 Portland, 121 Roman, 121 Ceramics, 120 Cerium, 176, 177 Cesium, 177 Chain closed, 210 open, 210 Chalk, 135 Changes, chemical, 6 physical, 6 Charcoal, 28 Chemism, 3 Chemical change, 187 Chemistry, 6 of carbon compounds, 202 compound radicals, 201 electro 179 organic, 201, 205 scope of, 203 physical, 179 Chestnut tannin, 496 Chicle gum, 548 Chili niter, 151 Chloral, 250, 336 antidote for, 587 alcoholate, 337 formamid, 339 hydrate, 337 properties of, 337 Chloralamid, 339 Chloralose, 339 Chlor benzene, 444 Chloric ether, 256 Chloroform, 249 antidote for, 587 purity tests, 252 Chlortoluene, 434 Chlorin, 34 acids, 35 compounds, 35 oxids, 35 preparations, 34 properties, 34 Cholesterol, 296 Cholin, 284 Chromium, 122 acids, 122 alloys, 122 anhydrid, 122 compounds, 123 pigments, 123 preparation, 122 properties, 122 sulfate, 123 toxicology and tests, 124 Chrome alum, 497 green. 124 598 I Chrome yellow, 123 Chromic chlorid, 124 Chromyl chlorid, 124 Chrysamin, 446, 447 Chrysarobin, 497, 499 Chrysene, 407 Cinchonism 579 Cinchonidine, 533 Cinchonine, S33 Cineol, 551, 5S4, SS5. SS6 Cinaldehyd, 476 Citral, S49. 556 Citrene, S4S Citronellal, 556 Citronellol, 548, 549. 55^ Classification, 8 of compounds, 15, 211 Closed-chain series, 407 Clovene, S47. SS4 Coal distillation, 410 gas, 245 Coal tar, 407, 408 Cobalt, 1 25 compounds, 126 inks (sympathetic), 126 Cocaine, 532 law, 589 Codeine, 533 Cohesion, 3 Coke, 29, 407, 409 Colchicine, 534 Colchicum antidote, 586 Collidin, 541 Collodion, 321, 405 Colophene, 544 Colophony, 503 Combustion tube, 536 Concrete, 121 Congo red, 447 Coniine, 531 Conium poisoning, 587 antidote, 587 Copaiba, 505 adulteration, 505 Copal, 503 Copper, loi compounds, 102, 104 properties, 102 salts antidote, 586 tests, 1 04 toxicology, 104 Cordite, 290, 404 Cork, 406 Corrosive acid poisoning, 582 antidotes, 586 Cotton, 403 Cottosuet, 295 Coumarin, 492 Creatin, 385 Creatinin, 385 Creolin, 45s Creosol, 466 Creosote, 455 Cresol, 434. 454. 455 compound solution, 455 para, 408 propylmeta, 457 Crcsylic acid, 454 Croton chloral hydrate, 339 Cryolite, 151 Cryoscopic method, 576 Crystal violet, 360 Cubebin, 544 Cudbear, 467 Cumene, 417a Cutch, 417a tannin, 496 Cyamelide, 378 Cyanhydrins, 330, 396 Cyanic acid, 316 Cyanid, 212 poisoning, 582 antidote for, 311, 587 Cyanogen, 30, 310 compounds, 310 Cyanuric acid, 316 Cyclic hydrocarbons, 407 Cymene, 417a, 434, 443. 545 hexahydroxy, 549 Dammar, 503 Dead oil, 410 Decay, 274 Deliquescent, 185 Density vapor, determination of, 576 Dermatol, 493 Determination, vapor density, 576 molecular weight, 571 Dextrin, 394, 402, 405 Dextrose, 394, 398 Diamins, 441 Diamin tetramethylene, 541 pentamethylene, 541 Diaminodiphenyl, 446 Diamond, 27 Diamyl ketone, 340 Diastase, 267 Diazoamido compounds, 447 Diazobenzene, 442 butyrate, 443 chlorid, 450 hydrochlorid, 443 nitrate, 443, 444 sulfate, 443 Diazo compounds, 418. 442 Dibromanthroquinon, 522 Diethyl-glycocol-amido-oxyben- zoic methyl ester, 491 Diethyl ketone. 340 Diethylsulfondiethylmethane, 343 599 Diethylsulfondimethylmethane, Digitalein, 500 Digitalin, French, German and Killiani, 500 Digitoxin, 500 Digitalis poisoning, 581 antidote, 587 Dihexyl ketone, 340 Dihydroxytoluene, 466 Di-isopropyl ketone, 340 Di-isobutyl ketone, 340 Dimethylamin, 386 Dimethyl aniline azo benzene sulfuric acid, 429 Dimethyl ketone, 340 Dimorphous, 184 Dipentene, 546 Diphenylamin, 437 Diphenyl ether, 452 Diphenyl ketone, 479 Dippel's oil, 436 Dipropyl ketone. 340 Distillation applied, 558 Distillation, dry, 245 destructive, 245 Diuretin, 535 Dog buttons, 534 Dragon's blood, 507 Dried gypsum, 139 Dulcitol, 306 Durene, 4176 Dutch liquid, 241 Dyes, 468 colloidal, 470 Dyeing, 468, 469 Dynamite, 290 Ebonite, 512 Efflorescent, 185 Elastica, 512 Elaterin, 497, 498 Electrolysis, 180. Electrolyte, 180 Electro-negative, 179 Electroplating, 181 Electro-positive, 178 Electrotypes, 181 Electrotyping, 180 Elements, 4 Elementary matter, 4 Elements and compounds, 10 Elements, classification of, 169 Elemi, 503 Emetics, classification of, 584 Enfleurage, 552 Enteric pills, 491 Eosin, 461, 462 Epicarin, 516 Epsom salts, 166 Equations, 187 analytic, 189 Equations, double decomposit- ion, 191 single decomposition, 190 synthetic, 189 writing, 187 rules, 188, 191 Erlenmeyer's formula, 513 Erythritol, 301 Esparto, 469 Essence, fruit, 321 Essential oils, 544 constituents of, 548 Ester, 317, 323 Ethane, 229 density of, 376 derivatives of, 255 Ether, 317 antidote for, 587 preparation of, 318 compound, 317 properties of, 320 spirit of, 321, spirit compound, 321 sulfuric, 320 Williamson's synthesis of, 318 Ethereal oil, 325 Ethers, table of, 317 Ethyl acetate, 323 alcohol, 274, 275 aldehyd, 335 benzene, 408, 41 7a benzoate, 484 bromide, 257 carbonate, 325 chlorid, 256 density of, 576 cyanid, 355, 376 ether, 206 iodid, 256, 323 mercaptan, 342, 381 naphthalene, 515 nitrate, 375, 323 phenylether, 452 sulfate, 325 sulfite, 373 sulfonic acid, 3S1 toluenes, 417a Ethylamin, 442, 3 75 Ethylene, 238, 239, 242 series, 237 diamin, 283 glycol, 3S9 Ethylene oxids, 283 Ethylidene chlorid, 256 Eucalyptol, 551 Eugenol, 549, 551, 554, SS6 Euphorbin, 512 Euphorbium, 512 Extraction (vegetable), 40s Extracts (perfume), 477 6oo Factors, 187 Fats, 291 adulteration of, 293 analysis of, 293, 294 composition of, 292 liquid, 291 preparation of, 293 properties of, 293 preservation, 294 purification of, 294 solid, 292 Fatty acid, series, 347 acids, table of, 345 Feathers, 469 Fermentable sugars, 398 Fermentation acetic, 267 alcoholic, 267 Fermentation lactic, 268 requisites of, 270 vinous, 267 Ferments, 266, 267 Fixed oik. 292 Fitiig's reaction, 424, 429 Fibers, 468 animal, 468 preparation of, 468 vegetable, 468, 469 Flame, Bunsen, 247 gas, 246 oxidizing, 246 reducing, 246 Floral waters. 552 Fluorin. 32 compounds, 33 properties of, 32 Fluorescein, 461 Formaldehyd, 333 Formic acid series, 347 Forcite, 290 Formose, 334 Formulas, chemical, 14, 182 constitutional, 236 empiric, 183, 236, 563 calculation of, 569 graphic, 236 molecular, 183, 236 rational, 236, 571 structural, 236 type, 183 Frankincense, 510 Freezing-point, method, 576 Friedel and Crafts reaction, 425 Fruit oils, 321 Fructose, 394, 399 Furfurol, SS4 Gadinine, 541 Gas, carburetting, 409 composition of, 409 manufacture, 408, 409 purification, 409 Gaseous state, 575 Galactose, 394, 399, 400 Galactozone, 399 Galbanum, 511 Gallalith, 334 Gamboge, 511 Gallic acid, 471 Garantose, 486 Gelatin, 542 blasting, 290 explosive, 290 General formulas, 224 Geranial, 549 Geraniol, 548, 556 acetate, 548, 556 esters, 548 Geranyl-acetate, 536 Gin, 244 Glass, water, 47 soluble, 47 Glonoin, 289 Glucose, 394, 397, 398 Glucosid, 497 Glucozone, 397 Glusin, 486 Glycols, 284 Glycin-ammonia, 384 Glycocol, 384 Glycogen, 394, 403 Glycollic acid, 282 aldehyd, 282 Glyoxyl, 282 Glyoxallic acid, 282 Glycerins, 285 Glycerol, 285 Glyceryl, 287 Glycosids, 497 nomenclature of, 49? Glycosid, 497 Goa powder, 499 Gold, 174 Goulard's extract, 354 Granulose, 402 Graphic formulas, 231 Graphite, 27 Gray lime, 341 Green, benzaldehyd, 464 Brighton, 404 Brunswick, 404 malachite, 464 mountain, 104 Neuwieder, 104 Paris, 103 Scheele's, 104 verdites, 104 Grignard's Reaction, 308 Guaiacol, 456, 461 carbonate, 457 Guanidin, 392, 534 Guanin. 391, 392, 393 Guaranine, 534 Gum, chicle, 548 Gums, 394, S02 6oi Gums, natural, 504 resins, 509 Gun-cotton, 404 soluble, 404 Gutta-percha, 544, 548 Gypsum, 135 Halogens, 31 hydracids, 32 oxacids, 32 oxids, 32 Hartshorn, 162 Hair, 469 Hawthorn oil, 47 7 Heavy oils, 407, 410 spar, 132 Headache powders, poisoning with, 58 Helianthin, 428, 429 Heliotropin, 478 Hemellithine, 417a Hemlock tannin, 496 Henbane, 587 Heptoses, 396 Hesperidin, 545 Heterocyclic, 527 Hexahydroxycymene, 549 Hexamethylene, 417 tetramin, 417 Hexamethylenetetramin, 332 Hexamethyleneamin, 417 Hexylene, 239 Hexoses, 396 Hoffman's anodyne, 321 Homatropin, 532 Homologous series, 184 Homology, 214 Holocain, 459 Homocyclic substance, 527 Humulene, 547 Hydracids, 16 Hydroxylamin, 379, 396 Hydrazin, 380, 444 Hydrazins substituted, 439 Hydrazo benzene, 446 Hydroquinone, 460 Hydrazin benzene, 380 Hydtazones, 380, 396, 397 Hydrocarbons, halogen deriva- tives of, 258 hydroxids of. 260 Hydrochloric acid, density of, 576 Hydrocyanic acid poisoning. 582 antidote for, 587 Hydrocarbons, 211, 214 properties of, 216 synthesis, 217 Hydrocollidin, 541 Hydroxy-aldehyd, 39s Hydroxy-anthroquinones, 522 Hydroxy-benzene, 438 Hydroxy-ketones, 395 Hydroxy-napthalene, 515 Hydroxy-toluenes, 434, 454 Hydrolysis, 268 Hydrogen, 18 compounds, 18 determination of, 563 preparation, 19 properties, 18 Hypnal, 339 Hypnone, 479 Hypo, 17 Ichthyol, 453 Idiosyncrasy, 579 Imido compounds, 387 Immunity, 542 Indium, 176 Indigo, 463, 464, 468 brown, 463 synthesis, 463 Indigotin, 463 blue, 470 Indicator, 567 Indoxyl, 464 Ink-blacks, 470 Inorganic and organic, 7 Invertase, 267 Inulin, 394, 402 lodol, 53 5 Iodoform, 254 lodin, 37 antidote, 586 number, 294 preparation, 37 poisoning, 582 properties, 37 solution compound, 38 lodism, 579 Ion, 178 Ionic theory, 179 Ion, polarity of, 179 Irregular, 422 Iron and ammonium sulphate, 115 cast, no chlorid, 114 compounds, 112 dialysed, 116 distinction, 117 ferrocyanid, 313 hydroxid, 114 with magnesia, 115 hypophosphite, 115 liquor, 354 pig, no reduced, 112 sulfate, 113 tests, 116 welded, no wrought, no 6o2 Iridium, i7S Iso, 282 Isoamylene, 241 Isobutyrone, 340 Isobutyronitril, 356 Isocyanids, 376 Isologous series, 184 Isomerism, 123, 23s, 421 Isomeric, 206 Isomorphous, 185 Isonitroso compounds, 380 Isonitril, 439 Isopentane, 233 Isoprene, 554 Isopropylcyanid, 356 Isoquinolin, 530 Jeaunel's universal antidote, 581 ute, 469 Kainite, 151 Kauri gum, 503 Kekule's theory, 414 Ketone-diphenyl, 479 Ketones, 211 hydroxy, 391 table of, 340 triose, 39S structure of, 330 Ketols, 342 Ketoses, 395 isomeric, 396 Ketoximes, 331, 380 Kolanine, S3S Kolbe's synthesis, 482 KjeldahVs method, 565. s66 Lactose, 394. 400 Lactophenin, 459 Lactone, 492 Ladenburg's prism, 41 S "Lager," 272 Lakes, violet, 523 brown, 523 red, 523 purple, 523 orange, 523 Lakes, 468 Lampblack, 29 Lanolin, 296 Lanthanum, 176 Lard, 294 Laurin, 291 Law of octaves, 109 Lead, 82 acetate, 354 black, 27 properties, 63 toxicology of. 83 compounds, 84 salts, poisoning with, 582 antidote for, 586 Leather, 497 chrome, tanned, 497 Leblanc's process, 155 Leucin, 385 Leuco-base, 464 indigotin, 470 Levulose, 394- 398, 399 Leukomains, 541 Lignin, 403 Light oils, 407. 410 Lignite, 28 Linalool, 548 esters, 548 Linalal, 555 Linalyl acetate, 554. 55" Limonine, 545. 5 46 hydrochlorids, 545 tetrabrom, 545 Lime clays, 120 stone, 135 light, 136 chlorinated, 137 sulfurated, 137 water, 137 Liquor chlori compositus, 34 Lithium, 141 properties of, 141 compounds, 141. 142 Litmus, 467 Liver of sulfur, 151 Lobeline, 531 Logwood black, 468 Lye, 146 Lydite, 4 54 Lysol, 455 Madder, 522 Magenta arsenate, 464 Magnesia, heavy, 167 light. 166 Magnetite, 109 Magnesium, 166 arabinate, 503 ..as Magnesium compounds, iO-^mOS tests for, 168 Maltose, 394. 40i Manganates, 127 Manganese, 127 black oxid, 127 hypophosphite, 128 compounds, 128 ores, 127 sulfate, 128 Manganite, 127 Mannitol, 306 Mannose, 394 Margarin, 291 Mass, 2 Mastic, 503, 504 Matter, i aggregation, 2 continuity of, 2 6o3 Melitotriose, 394 Mendelejeff's classification. 170 Menthyl acetate, 556 Menthol, 548, S49. 55^ Menthone, 549 Menthyl-monyl-ketone, 549 Mercaptans, 380 Mercaptids, 381 Mercaptols, 342 Mercerized fiber, 404 Mercurialism, 579 Mercuric chlorid, 105 poisoning, 582 antidote for, 586 compounds, 105, 107 fulminate, 377 iodid, red, 106 oxid, red, 107 thiocyanate, 379 Mercury, 79 black oxid of, 82 chlorid, mild, 81 compounds, 81 green iodid, 81 mild chlorid, 81 nitrate, 82 preparation of, 79 properties of, 79 tests for, 80 toxicology of, 80 yellow oxid, 81 Mesitylene, 342, 408, 417, 433 Mesitylic acid, 433 Metals, 8, 76 atomic weights of, 178 noble, 17s rare, 174 refining of, 181 symbols of, 178 table of, 176 valences of, 178 Metalloids, 8 Metamerism, 235 Metaphenylene diamin, 442 position, 421 Methane, composition of, 219 derivatives of, 248 homologues of, 227 Methoxybenzoic acid, 452 Methyl-acetaniUd, 439 Methyl -amin, 377, 382 hydrochlorid, 387 ammonium bromid, 386 anthracene, 408 anthranilate, 454 benzoate, 483, 484 bismuth, 390 cyanid, 376 di-iodo salicylate, 491 di-oxytoluene, 446 ethyl-benzene, 417a ether, 321 Methyl-ester of amido-hydroxy- benzoic acid, 491 glycin, 385 guanidin-acetic acid, 385 Methyl isocyanid, 377 mercaptan, 381 mercury, 390 naphthalin, 515 nonyl-ketone, ss6, 557 orange, 429 phenols, 454 platinum chlorid, 388 salicylate, 324, 389, 492, 554, 555 sulfonic acids, 381 tin, 390 Methylene-blue, 465 Meyers' Victor, Method of, 576 Milk of hme, 137 Mixtures, 9 Molecule, 2 Molecular weight, 12 determination, 571 by Avogadro's law, 574 Molybdenum, 175 Monomorphous, 184 Mordants, 464 Morphine, S33 poisoning, 582 antidote for, 587 Mortars, 120 Mother of vinegar, 351 Muriate of ammonia, 163 Mushroom poisoning, 582 Mutton suet, 294 Mylitoxin, 541 Myrcene, 556, 546 Myristin, 291 Myristicol, 556 Myrobolans-tannin, 496 My rosin, 267 Myrrh, 510 Naphthalin, 408 Naphthols, 516 Naphthol salicylate, 492 Naphthyl, 516 Naphthylamins, 517 Naphthalin-sulfuric acids, 517 Naphthaquinones, 518 Naphthalin derivatives, 513, 519 Narcotine, 533 Natural gas, 220 Neutral principles, 497 Neuridin, 541 Neurin, 284, 541 "Neutral mixture," 147 Newland's classification, 170 Nicotine, 531 Niccolite, 126 Nickel, 126 6o4 Nigrosin, 468 Niobium, 176 Niobe oil, 484 Nirvanin, 491 Nitrogen, 24 determination of, 5 "5 in organic compounds, 37, preparation of, 24 properties of, 24 oxids, 25 Nitrils, 307. 375 Nitro-benzene, 374 benzaldehyd, meta, 470 Nitrocellulose, 404 Nitrocelluloses, 404 Nitroderivatives, 37S Nitro-ethane, 37S glycerin, 289 methane, 374 naphthalins, 517 paraffins, 3 74 Nitrosamin, 439 Nitroso-methylanilm, 439 Nitrophenols, 453 Nitrotoluene, 435 Nobel's oil, 289 . , „ Nomenclature, chemical, 182 Nonmetals, 8, 18 Nux vomica, 534 poisoning, 582 antidote for, 587 Oak-tannin, 496 Octoses, 396 CEnanthone, 340 Oil, Dippel's, 515 Oil of almonds, bitter, 554 anise, 554 allspice, 556 bay, 546, 556 bergamot, SS4 birch, 325 cade, 507, 554 cajuput, 554 cassia, 476 caraway, 554 cinnamon, 476, 555 cloves, 554 copaiba, 55 5 coriander, 555 cubeb, 555 erigeron, 555 eucalyptus, 55 5 fennel, 555 fleabane, 555 gaultheria, 555 garlic, 284 juniper, S55 lavender, ss^ flowers, 556 lemon, 556 lilac, 547 Oil o£ meadowsweet, 476 mirrbane, 426 mustard, 379. 557 myristica, 556 neroli, 554 nutmeg, ss6 orange flowers, 554 peel, 554 pennyroyal, S5 5 peppermint, S5<> pimenta, 556 roses, 556 rosemary, 557 rue, 557 , sandalwood, 55" sassafras, 557 savin, 557 spirea, 476 spearmint, 556 sweet birch, 554 syringa, 547 tar, 507 thyme, 557 turpentine, 557 valerian, 55 7 wintergreen, 555 synthetic, 324 wormseed, American, 556 Oils, volatile, adulteration of. difference from fixed, 550 drying, 297 essential, 549 fish, 297 intermediate, 297 nondrying, 297 oxygenated, 550 sulfurated, 5 5° terpenes, 550 . volatile, discussion, 549 Olefin, 237 Olefins, table of, 238 properties of, 239 nomenclature of, 242 Olein, 291 Oleo oil, 296 Oleomargarin, 295 Oleoresins, 503, 504 Olibanum, 510 Optical activity, 390 Oppoponax, su Opium, 538 poisoning, 582 antidote for, 587 Orcein, 467 Orcin, 467 Orcinol, 467 Orchide^, 476 Organic analysis, 556, 5p3 substances, behavoir witn immiscible solvents, SS9, 561 6o5 Organic compounds, classifica- tion of, 211 Organo-metallic compounds, 213. 389 Ortho-position, 421 dinitrobenzene, 442 hydroxycinnamic acid lac- tone, 492 phenylenediamin, 442 Orthoform, 491 Orphol, S16 Osazones, 380 " Ose," 39S Oxacids, 17 Oxalic acid, 282, 586 Oxalyl group, 347 Oxids, acid, 22 basic, 22 neutral, 22 Oxinies, 380, 398, 399 Oxaldehyds, 476 Oxyhydroquinone, 472 Oxygen, 20 determination of, 569 preparation of, 21 properties, 22 Ozone, 23 preparation of, 23 Palladium, 176 Palmitin, 291 Papayotase, 267 Papaverine, S33 Paper, 406 calendered, 406 unsized, 406 parchment, 404 Para-acetphenetidin, 458 Para-amidophenol, 458 Paraldehyd. 535 Para-nitrophenolethylether, 45S Para-phenetidin, 458 Para position, 421 Para rosanilin hydrochlorid, 46s Parchment paper, 404 vegetable, 403 Paris green, 103 white, 138 Paraffins, iso, 234 neo, 234 nomenclature of, 223 normal, 234 primary, 234 secondary, 234 table of, 221 tertiary, 234 Pearl ash, 145 Peat, 28 Pennsylvania poison law, 585 588, 589 Pental, 241 Pentamethylenediamin hydro- chlorid, 528 Pentoses, 396, 472 Pepsase, 266 Peptone, 542 Per, 17 Periposition, 518 Periodic Law, 169 Perkin's reaction, 488 Petroleum, 28, 222 fractions of, 223 industry, 221 theory of formation of, 215 Pharaoh's serpents, 379 Phellandrene, 544, 555, 556, Phenacetin, 458 poisoning, 582 Phenanthrene, 520, 525, 526 Phenetol, 452 Phenocoll, 4S9 Phenol, 408, 438, 444 alcohols, 473 aldehyds, 476 antidote (same as Vegetable acids) ethers, 451 derivatives, 452 meta-dihydroxy, 460 orthodihydroxy, 460 paradihydroxy, 460 sulfuric acids, 432 Phenols, 408, 449. 45° diatomic, 449. 460 monatomic, 449 nitric, 453 triacid, 45° triatomic, 449. 47i Phenyl, 430 acetate, 452 Phenylamin, 435 Phenyl carbamid, 439 cyanid, 440, 485 P henylglucosazone, 397. 399 Phenyl hydrazin, 380, 396, 444. 448 hydrochlorid, 444. 445 hydrazone, 331, 397 hydrosulfid, 454 isonitril, 439 mercaptan, 454 methane, 429 methylether, 451 methylketone, 478 salicylate, 490 Phloroglucinol, 471 Phosgene, 359 Phosphin, 388 dimethyl, 388 methyl, 388 trimethyl, 388 Phosphonium, 388. 389 hydroxid, 389 6o6 Phosphonium, tetramethyliodid, 389 Phosphorus, 42 acids, 44 antidote for, 587 compounds, 44 determination of, 569 poisoning, 583 preparation of, 43 properties of, 43 Phthalimid, 487 Phthalic acids, 487 anhydrid, 487 Physical science, s Physics, 5 Physiologic antagonists, 580 Physostigma, antidote for, 587 Physostigmine, 534 Plaster of Paris, 139 Platinum, 174 Plumbago, 27 Plumblism, 579 Poirrier's orange, 429 Picolins, 529 Picrotoxin, 497, 499, 501 Pills, enteric, 491 Pinene, 544 Pilocarpine, 534 Piperidine, 528, 531 Piperine, 531 Piperonal, 478 Podophyllotoxin, 497, 501 Poison, corrosive, 577 cumulative, 578 definition of, 578 irritant, 578 law, Pennsylvania, 585, 588 589 mechanic, 578 true, 577 Poisoning, acute, 579 chronic, 579 methods of treating, 583 ptomain, 582 unknown, treatment of, 580 Poisons, antidotes for, 586, 587 effects of, 578 toxic action of, 578 Pole, negative, 178 positive, 178 Polymerism, 184, 235 Polymorphous, 184 Pomegranate tannin, 496 Porcelain, 120 Porter, 274 Potash, 146 Potassium, 142 benzoate, 484 binoxalate, 364 carbazole, 520 compounds, 143, 151 cyanate, 315, 378 Potassium, cyanid, 313 ferricyanid, 312 ferrocyanid, 148, 311 hydroxid, 143 hyi)ohosphite, 148 iodid, 149 permanganate, 128 phenolate, 452 preparation of, 143 properties of, 143 sulfobenzoate, 450 sulfocyanid, 315 Pottery, 120 Prehnitine, 4173 Propane, 228 Propione, 340 Propionitril, 376, 387 Propionyl chlorid, 371 Propylamin, 387 Propylene, 238 Proteins, 212, 542 Prussiate of potash, yellow, 148 Pseudocumene, 408, 417a Ptomain poisoning, 582 Ptomains, 538, 541 Pulegone, 555 Purification of organic com- pounds, 558 Purple of Cassius, 175 Purpurin, 524, 525 anthra, 524, S2S flavo, 524, 525 Putrefaction, 543 table of, 543 Putrescin, S4i Pyoktanin, 466 Pyrazalone, 535 Pyrazol, 535 Pyrene, 407 Pyridin, 408, 527, 528, 529 derivatives, 531, 532 tetramethyl, 541 trimethyl, 541 Pyridins, dimethyl, 5^9 methyl, 529 trimethyl, 529 Pyrocatechin, 460 Pyrocatechol, 460 dimonomethyl carbonate, 457 methylene ether of, 55 1 monomethyl, 45 7 Pyrochromic mixture, 355 Pyrrol. 408 derivatives of, S3S Pyrogallol, 470, 471 Pyroxyllins, 404 Quantivalence, 13 Ounssi metal, 161 Ouaternary phosphonium, 389 (Juercitrin, 497, 501 6o7 Quick lime, 136 Quinidine, 533 Quinine, 533 Quinol, 460, 467 Quinolin, 408, 529, 53° derivatives, 532, 533. 534 Quinone, 467 Quinones, 479- Roffinose, 394. 401 Ramnose, 501 Reaction, 6, 187 Adamkiewicz s, 542 Biuret's 542 Millon's 542 xanthoproteic, 542 Sandmeyer's, 485 Reactive bodies, 187 Reagent, 187 Rectification, 273 Red, Congo, 44 7 liquor, 354 prussiate of potash, 14a Turkey, 468 Reimer's synthesis, 476 Rennin, 267 Resin of guaiac, 503, 504 Resins, 503 balsamic, 503 Resorcin, 460 phthalin, 461 Resorcinol, 460, 461 Rhodamins, 462 Rhodium, 176 Rochelle salts, 147 Rosanilin, 440, 464. 47° Rosin, S03 soap, 547 Rosolic acid, 463 Rubber, S12, 548 para, 512 Rubidium, 177 Rum, 274 Ruthenium, 176 Saccharids, 396 Saccharin, 486 Saccharoses, 394 di, 394 mono, 394. 390. 398 poly, 394, 402 tri, 394. 396 Safrol, SSI. 557 Salacetol, 326 Salacin, 497. 499. 474 Sal ammoniac, 163 Salantol, 326 Saleratus, 144 Salicylal, 476 Saligenin, 474 SaHpyrin, 491 Salol, 490 Salophen, 491 39 Salt, 183 of sorrel, 364 Saltpeter, 150 Sal tartar, 145 Salts, scale, 1 1 s Sal volatile, 162 Sandarac, S03 Sandmeyer's reaction, 485 Sanoform, 491 Santalol, S48, 557 Santonin, 497. 499 antidote for, 587 poisoning, 582 Saponification, 332 value, 294 Sarcosin, 385 Saturnism, S79 Scale salts, 1 1 5 Scammony, 511 resin, 512 Scandium, 176 Scarlet, Bieberich, 44 7 Scopolamine, 532 Seidlitz powder, 148 Seignette's salt, 147 Selenium, 47 Shellac, 503 "Side chain," 425 Siderite, 109 Silicon, 46 compounds, 46 Silk, 469 artificial, 405 Silver, 85 compounds, 86, 88 cyanid, 314 isocyanid, 377 nitrate, antidote for, 587 poisoning, 583 Sinigrin, 497 Soaps, preparation of, 85 hard, 288 Soaps, insoluble, 289 soft, 288 Soda, 151 saleratus, 153 Sodium, 151 acetate, 152 arsenate, 152 benzoate, 153 bicarbonate, 153 bisulfite, 153 Sodium bromid, 154 carbonate, dried, 155 monohydrated, 154 chlorate, 156 chlorid, 156 citrate, 156 dried, 152 hydroxid, 151 hypophosphite, 156 ichthyosulfonic acid, 453 6o8 Sodium iodid, 157 nitrite, 157 nitrate, 157 nitroethane, 375 nitroprussid, 379 orthoborate, 154 oxalate, 364 phenolate, 408, 489 phenolsulfate, 158 phenolsulfonate, 453 phenylcarbonate, 489 phosphate, 158 dried, 159 preparations, 159 pyrophosphate, 159 salicylate, 159, 489, 490 sulfate, 160 sulfite, 160 sulfocarbolate, 453 thiosulfate, 160 Solids, liquids and gases, s Solution, standard, 565, .<;66 Solvay's process, 153 Solvents, 558 Sorbinose, 394 Sorbitol, 306 Sparteine, 531 Spelter, 129 Spiegeleisen, 11 1 Spirit of nitrous ether, 324 Spirits, Colonial, 265 Columbian, 265 Eagle, 263 methylated, 265 Standard solution, 565, 566 Starch, 394 Steam, density of, 576 Stearin, 291 Stearoptenes, 551 Steel. 1 10 Bessemer, 1 10 description of, 112 open-hearth, it i Siemens-Martin process, III Stibin, 388 trimethyl, 389 Stibonium, 388 Stimulants, 588 Stoichiometry, 196 Stoneware, 1 20 Storax, 509 Strammonium, antidote for, s87 Straw, 469 Strontianite, 133 Strontium. 133 compounds, 134 description of. 134 tests, 134 Strophanthin, 497, 500 Strychnine, 534 antidote for, 587 Strychnine, poisoning, 382 Styrax, 509 Sty rone, 473 Suberin, 406 Substitution, addition, 224 of acids, 383 products, 220 Succinamid, 36s Succinum, 504 Sucrose, 400 Sugar, 394 cane, 394, 400 fruit, 394 grape, 394 house syrup, 400 invert, 398 malt, 394 milk, 394, 401 of lead, 354 Sulfonal, 343 Sulfonic acids, 381 Sulfovinic acid, 319 Sulfonmethane, 343 Sulfonmethylmethane, 343 Sulfur acids, 42 alcohols, 380 compounds, 42 derivatives, organic. 380 determination of, 569 ethers, 382 group, 39 iodid, 41 precipitated, 44 preparation of, 40 properties of, 40 Sulfurated potash, 151 Sumach tannin, 496 Sylvite, 142 Symbols, 11 Symmetric, 421, 471 Symptoms suggesting common poisons, 581, 582, 583 Synaptase, 267 Tan liquor, 496, 497 Tanning, 496 Tannins, 494. 495 Tantalum, 176 Tar, S07 Tartar emetic, 304 Taurin, 284 Tautomeric, 39s Tellurium, 47, 17s Tercbenc, 547 Terebenthene, 545 Terpcne, 408, SSS. Sh(>. S.S7 Terpenes, 544 di. 544 hemi, 544 poly, 544. 548 sesqui, 544. 546 Tcrpinene, 547 6o9 Terpineol, S47. SSS. SS7 Terpin hydrate, 547 Terpinolene, 547 Terra alba, 139 Tests for carbon, 561 halogens, 562, 563 hydrogen, 562, 563 nitrogen, 561, 562 phosphorus, 563 sulfur, 563 Tetrabromfluorescein, 462 Tetronal, 344 Tetroses, 396 Thalium, 174 Thebaine, 533 Theine, 393. 534 Theobromine, 393. S3S Thiophene, 413 Thiophenol, 4S4 Thorium, 176 Thymol, 457, 549. 557 Tin, 96 acids of, 97 oxids of, 97 preparation, 96 properties of, 96 tests for, 97 Titration, 567 Titanium, 176 Titre, 56s Toluene, 429 derivatives, 429 metachlor, 431 orthochlor, 431 parachlor, 431 Toluic acids, 432, 486 Toluidins, 440 Toluol, 408, 417a, 459 brom-, 424 Toluyl chlorid, 434 Toxicology, 577 Toxins, 541 Tragacanth, 502 Treatment of unknown poison- ing, 580 Tricarballylic acid, 300 Trichloraldehyd, 336 Trichlorhydrin, 286 Trihydroxyanthraquinone, 524 Trimethylamin, 386, 387 Trimethylaramonium iodid, 388 Trimethylbenzene, 342, 433 Trimethylglycin, 38s Trimethylxanthin, 393 Trimorphous, 184 Trinitrin, 289 Trinitrophenol, 454 Trional, 343 Triphenylmethane, 466 Tfiphenylrosanilinhydrochlorid, 46s Tristearin, 288 Trypsase, 266 Trypsin, 266 Tungsten, 174 Turkey red, 468, 523 Turpentine, American, 545 Canada, 506 Chian, 506 Cyprian, 506 French, 545 oil, 545 Strassburg, 506 Venice, 506 Turpentines, 506 Tyrotoxicon, 443 Universal antidote, Jeaunel's 580 Unknown poisoning, treatment of, 580 Uranium, 176, 177 Urate, ammonium, 391 lithium, 391 Urea, 203, 360, 362, 391 oxalyl, 391. 392 Urethane, 325 Uvitic acid, 433 Valence, 13, I79 of elements, 186 variable, 14 Vanadium, 176 Vanillin, 477, 478 sugar, 478 Vapor density, determination of 576 Varnish gums, 298 manufacture, 298 Veratrine, 534 Veratrum, antidote for, 587 •Ventilation, 63 Verdigris, 103 Vicinal, 471 Victor Meyer's method, 576 Vienna lime, 144 Vinegar, 351 process, quick, 352 Violet, crystal, 466 methyl, 466 Volatile oils, constituents of, 554, 557 preparation 01, 552 table of, 554 Volumetric analysis, 566 solution, 566 Vulcanite, 512 Vulcan powder, 290 Water, 48 analysis, 57, 60 • atmospheric, 50 ground, 52 hard (temporary), 52 (permanent), 52 6io Water, lake, 53 Xanthin, 391, 392 mineral, so, S4 derivatives of, S34 ocean, 54 dimethyl, 393 pond, 53 trimethyl, 393 potable, 56 Xylene, 424 ' rain, 51 derivatives, 431 river. S3 safe and dangerous. 57 meta, 431 ortho, 431 spring, SI para, 431 steam, 48 Xylenes, 431 terrestrial, so amido, 441 well, S2 Xylenol, 408 Waters, floral, SS2 Xylidins, 441 Wax, bees', 297 Xylitol, :,o6 Brazil-nut, 297 Xylols, 408 Chinese, 297 myrtle, 297 palm, 297 spermaceti, 297 Waxes, 297 'Welsbach burner, 247 Yellow, Martin's, 518 naphthol, 518 prussiate of potash, 14? Ytterbium, 176 Yttrium, 176 Whisky, manufacture of, 272 Zinc, 129 Whiting, 138 Zinc alloys, 131 Wine-lee's, ^02 blend, 129 Wines, 273 compounds, 130, 131 alcoholic strength of. dust, 129 274 ores, 129 Witherite, 132 salts, antidote for, s76 Wood, destructive distillation tests, :3i of, 265 toxicology of, 131 Wool, 468 Zirconium, 176, 177 fat, 296 Zymase, 266 2 OIO'^ f\ \Cp •% -■S* /- _ X