CLARK UNIVERSITY 
 
 '"lebration Lectures 
 
"> With flie compliments of the 
 Department of Chemistry, 
 C-LAKK UNTFER8IXY, 
 Worcester, - Mass, 
 
 fr 
 
 THE LIBRARY 
 
 OF 
 
 THE UNIVERSITY 
 OF CALIFORNIA 
 
 
 PRESENTED BY 
 
 PROF. CHARLES A. KOFOID AND 
 MRS. PRUDENCE W. KOFOID 
 
CHEMICAL ADDRESSES 
 
 Delivered at the Second Decennial Celebration of 
 
 CLARK UNIVERSITY, 
 
 ii 
 
 in September, 1909, 
 BY 
 
 Professor THEODORE W. RTCHA.RDS, of Harvard University; Professor WIUJAM A. 
 NOYBS, of the University of Illinois; Dr. WIMJS R. WHITNEY, Director of the Re- 
 search laboratory of the 'General Electric Company; Professor JOHN E. BUCHER, of 
 Brown University; Professor Juuus STiEGUTZ, of the University of Chicago; Dr. P. 
 A. SEVENS, of the Rockefeller Institute for Medical Research; Dr. EDWARD W. 
 WASHBURN, of the University of Illinois; Professor MARSTON TAYLOR BOGERT, of 
 Columbia University; Dr. C. S. HUDSON, of the U. S. Department of Agriculture; 
 Professor ARTHUR MiCHAKi,, sometime Director of the Department of Chemistry 
 in Clark University; Professor S. P. MULUKEN, of the Massachusetts Institute of 
 Technology; Professor H. P. TAiyBOT, of the Massachusetts Institute of Technology; 
 Mr. JESSE E. WHITSIT, of the DeWitt Clinton High School, New York; Mr. MICHAKI, 
 D. SOHON, of the Morris High School, New York; and Dr. ANDR DEBIERNK, of the 
 University of Paris. 
 
 With a Preface by 
 
 M. A. ROSANOFF, Sc.D. 
 
 Professor of Chemistry and Director of the Chemical Laboratories in Clark 
 
 University 
 
 Published jointly by Clark University, Worcester, Mass., and the American Chem- 
 ical Society. 
 
 1911. 
 
 . i. 
 
 I 
 
PREFACE. 
 
 Clark University was founded in 1889 as a research university, an insti- 
 tution in which the best part of the teaching and studying should be car- 
 ried on through original investigation. On the one hand, and primarily, 
 the University was to devote its activities to the advancement of scien- 
 tific knowledge. On the other hand, it was believed that genuine 
 knowledge and habits of independent thought can in no way be acquired 
 by the mature university student as surely as through the labor of finding 
 new truth. 
 
 While the new university has not perhaps attracted such attention 
 from the public at large as it would have received had it been attended 
 by large numbers of students, it soon gained a high reputation among 
 men of science both at home and abroad. It has been stated by good 
 authorities that the example of Clark University has had a profound in- 
 fluence on the ideals and organization of the American graduate schools 
 established since 1889.* 
 
 At the time of its foundation Clark University was almost unique in 
 this country in its ideals and methods. Even at present it can boast the 
 distinction of having none but research professorships : chairs unhampered 
 by the burdens of elementary teaching and routine administrative work. 
 If any member of the University, professor or student, fails to contribute 
 his share to the advancement of his science and thus himself gain greater 
 and greater mastery over it, the fault is not that of the University's 
 organization. 
 
 It seemed appropriate that the anniversary celebration of Clark Uni- 
 versity should consist in a series of research conferences, and the present 
 volume reproduces most of the chemical addresses of the Celebration. In 
 organizing the conferences, an effort was made to have all the more im- 
 portant chapters of American chemical research represented, and the effort 
 was in large measure successful, owing to the generosity with which a 
 majority of our chemical investigators responded to the Department's in- 
 vitation. 
 
 The technical addresses have been gradually publisned in the Journal 
 of the American Chemical Society, the educational addresses in Science. 
 
 *For example, Professor Stieglitz, reviewing the progress of American chemical 
 research, says: "The greatest recent impetus to all branches of research, including 
 chemistry, came, in my opinion, from the founding of Clark University, with research 
 as its chief and almost exclusive field...." (See Science, Vol. XXVI, p. 700, for 
 the year 1907.) 
 
 M3679G3 
 
The Chemical Department of the University wishes to again express its 
 deep appreciation of the honor bestowed upon it by the brilliant lecturers, 
 and its confidence that their joint effort here will not have been without 
 fruit. 
 
 The Department, which has recently been placed under the director- 
 ship of the present writer, also wishes to assure the chemists of the 
 country that it is making a veritable effort to grow to the ideal of 
 Clark University, which is the ideal of all sincerely scientific men. 
 
 M. A. ROSANOFF. 
 
 November. 1911. 
 
7 
 
 TABLE OF CONTENTS. 
 
 Page.* 
 I. Recent Investigations in Thermochemistry. By Professor Theodore W. 
 
 Richards X 
 
 II. Molecular Rearrangements. By Professor William A. Noyes 9 
 
 III. Organization of Industrial Research. By Dr. Willis R. Whitney 16 
 
 IV. The Acids of the Phenylpropiolic Series and Their Condensation to Naph- 
 
 thalene Derivatives. By Professor John E. Bucher 23 
 
 V. Catalysis on the Basis of Work with Imido Esters. By Professor Julius 
 
 Stieglitz 32 
 
 VI. On the Biochemistry of Nucleic Acids. By Dr. P. A. Levene 42 
 
 VII. The Fundamental Law for a General Theory of Solutions. By Dr. Edward 
 
 W. Washburn 52 
 
 VIII. A Review of Some Recent Investigations in the Quinazoline Group. By 
 
 Professor Marston Taylor Bogert 70 
 
 IX. A Review of Discoveries on the Mutarotation of the Sugars. By Dr. C. S. 
 
 Hudson 8 1 
 
 X. Outline of a Theory of Organic Chemistry Founded on the Law of Entropy. 
 
 By Professor Arthur Michael 87 
 
 XI. Progress in Systematic Qualitative Organic Analysis. By Professor S. P. 
 
 Mulliken 104 
 
 XII. The Outlook for a Better Correlation of Secondary School and College In- 
 struction in Chemistry. By Professor H. P. Talbot 113 
 
 XIII. High School Chemistry: The Content of the Course. By Mr. Jesse E. 
 
 Whitsit 125 
 
 XIV. Chemistry in Secondary Schools. By Mr. Michael D. Sohon 130 
 
 XV. Radioactivity. By Dr. Andre Debierne 135 
 
 *The numbers of this column arc to be found at the bottom of pages. 
 
RECENT INVESTIGATIONS IN THERMOCHEMISTRY. 1 
 
 BY THEODORE W. RICHARDS. 
 Received September 17, 1909. 
 
 Within a brief space of time, the world has lost two masters of thermo- 
 chemistry, Marcellin Berthelot and Julius Thomsen. To these great 
 men chemical science owes much ; their places in its history are forever se- 
 cure. Each, by his indefatigable labors, added both new methods and 
 new data to the sum of human knowledge; and upon the broad founda- 
 tion which they laid, all the subsequent development of thermochemistry 
 must be built. All honor to their memories! It is no discredit to their 
 faithful work that as science progresses many of their methods must be 
 subjected to revision and refinement, for mankind approaches precision only 
 little by little, and those workers who come later have the benefit of all 
 that has gone before, with fresh energy and new years with which to im- 
 prove upon it. In the same way, a few decades hence, others will perhaps 
 remodel the not yet perfect work of the present generation, may possibly 
 marvel at inaccuracies which have escaped our detection, and will have 
 opportunities for the exercise of charity similar to those which fall to our 
 own lot. 
 
 It is not necessary to emphasize the importance of thermochemistry, 
 or to trace in detail its history. You know that the first law of energy 
 was applied in this science by Lavoisier and Laplace, and by Hess, before 
 it was generalized by Mayer, Joule and Helmholtz. You are familiar 
 with the fact that Berthelot and Thomsen and Stohmann and others 
 utilized this principle to determine the heats of formation of most com- 
 mon substances with some degree of approximation; and that these data 
 constitute the sum and substance of our knowledge of the heat evolved 
 during chemical reaction. 
 
 Before we consider the revision of these multifarious data which is now 
 in progress, it is worth while to pause for a moment and think of their 
 significance. 
 
 Thermochemistry is concerned with the total energy-change of a chemical 
 reaction, and not with the change of the free energy, hence it cannot 
 serve as an infallible guide to the tendency of a reaction, for preponder- 
 ance of free energy, not of total energy, determines the path which a change 
 will take. Nevertheless, in spite of this limitation, thermochemistry 
 includes some of the most important facts of the universe within its scope, 
 both for the theorist and the practical man. 
 
 The total heat given out during any chemical change is one of the funda- 
 mental thermodynamic data concerning that change. Its exact evalua- 
 tion is necessary to the complete understanding of the thermodynamics 
 of any reaction, and without an understanding of the thermodynamics 
 of a reaction, the phenomena are only half interpreted. Although free 
 energy change is that which determines the tendency of the reaction, 
 bound energy is also significant, and the interpretation of bound energy 
 is being realized more and more generally as one of the coming problems 
 in thermodynamics. But bound energy is the difference between total 
 
 1 Presented at the Second Decennial Celebration of Clark University, Worcester, 
 Mass., on Sept. 16, 1909. 
 
 I 
 
1276 GENERAL, PHYSICAL, AND INORGANIC. 
 
 energy-change and the free energy-change, so that all these three quan- 
 tities are as closely connected together as is possible. In short, the ac- 
 curate determination of thermochemical data is essential to the precise 
 application of thermodynamics to chemistry. 
 
 To the practical man, perhaps, the matter takes on a different aspect 
 although ultimately he, too, will profit more than he can now appreciate 
 from the growth of pure thermodynamics. He is more immediately 
 concerned with the every-day applications of thermochemistry, espe- 
 cially the developments of heat by combustion. Our text-books of 
 chemistry discuss the union of carbon and oxygen with chief emphasis 
 upon the formation of carbon dioxide, but that is the least important 
 practical aspect of the matter. The really essential thing is the libera- 
 tion of energy, a fact which falls within the province of the thermochemist. 
 Numerous other reactions less striking but no less important, including 
 the maintenance of our own bodily heat, are concerned with the same 
 principles and methods. Hence it is not too much to say that thermo- 
 chemistry is intimately related with every breath we draw. The ac- 
 curate evaluation of its fundamental quantities is, therefore, one of the 
 most important fields of scientific advance, because accurate data are 
 needed to provide an adequate basis for precise thinking in an inductive 
 science. 
 
 Let us consider systematically the dimensions concerned, in order that 
 we may more clearly appreciate the advances which have been made 
 possible in thermochemical work during the years which have elapsed 
 since Berthelot and Thomsen carried out most of their work. The energy 
 of heat is, of course, calculated as the product of two factors, temperature 
 and heat capacity, and the accuracy of its determination is directly pro- 
 portional to the accuracy of measurement of each of these dimensions. 
 
 The advances in the accurate measurement of temperature during the 
 last thirty years have been very great. In the first place the standard 
 of reference, namely the hydrogen scale, has been fixed with much greater 
 accuracy than at that early time. There is very little evidence as to what 
 the centigrade degree, as used by Thomsen or Berthelot, really meant. 
 In the next place, the vagaries of the glass-mercury thermometer have 
 been studied by Crafts and others with much greater completeness and 
 understanding than in those earlier days. We know now how uncertain 
 its indications may be when it is not properly handled ; and we know, also, 
 how to obtain very accurate results from this instrument when it is prop- 
 erly made and carefully used. Again, thermometry has gained through 
 the introduction of new fixed points between the old classic ones of the 
 early history of thermometry; I mean the transition temperatures of 
 bi-component systems. These give a firm basis for a thermometric scale 
 in their neighborhood and thereby contribute to its certainty and defi- 
 niteness. All these things must be considered in the thermochemistry 
 of to-day and all contribute to an accuracy exceeding that of olden times. 
 
 A further gain has to be found in the introduction of the new methods 
 of measuring temperature electrically, which, when properly manipulated, 
 may exceed in accuracy the readings of the mercury thermometer. One 
 must not forget, however, that these methods are subject to their own 
 peculiar and somewhat elusive sources of inaccuracy, and that their use 
 does not yield the unqualified gain which is sometimes attributed to them. J 
 1 Emil Fischer and F. Wrede have made some excellent determinations in this way. 
 
RECENT INVESTIGATIONS IN THERMOCHEMISTRY. 1277 
 
 Turning now to heat capacity, we find that to some extent the same 
 considerations apply. Heat capacity is, of course, determined by com- 
 parison with a standard substance, and the comparison is made by means 
 of some kind of thermometer. The sources of error are partly eliminated 
 here, however, because the determination is a purely relative one and does 
 not hark back to the absolute standard, as in the case of temperature 
 change. Specific heats are reckoned by finding the rise of temperature 
 in two approximately equivalent masses of substance, one the standard 
 substance and the other the substance to be determined. If the same 
 thermometer is used in each and the quantities of substance are so ad- 
 justed that the temperature changes produced by a known quantity of 
 heat energy are nearly the same, the inaccuracies of the thermometer 
 are largely eliminated when the same thermometer is used as a standard 
 in each set of determinations. Errors of reading the thermometer still 
 appear, and indeed the range of inaccuracy here is doubled, because a 
 specific heat determination depends upon four thermometer readings 
 whereas temperature change depends upon only two. Obviously, how- 
 ever, an error in the standard interval makes no difference. The degree 
 might really be two degrees and its inaccuracy would cancel. Hence, 
 although the thermometer is used for determining heat capacity, the 
 uncertainties of the determination arise in part from a different source 
 and are chiefly to be traced to the errors of calorimetry, which deserve 
 and will receive detailed consideration in a few minutes. 
 
 Before discussing the errors of calorimetry let us for a moment discuss 
 the means of calculating the heat capacity of a given system which have 
 been used in the determinations now accepted by the chemical world. 
 We find upon studying the literature of the subject, that there has been 
 considerable variety of usage, but that the usage has rarely, if ever, 
 been precise. Marignac determined a number of specific heats by means 
 of a kind of calorifer, and Thomsen also determined many by means 
 of his combustion calorimeter, but these were seldom in either case within 
 two-tenths of one per cent. Therefore the values calculated from them 
 could not be expected to be closer than this, if as close, to the truth. 
 Work of others has not yet actually been used. Berthelot relied largely 
 on Marignac' s determinations or more commonly adopted very rough 
 approximations by assuming that the heat capacity of the solution is 
 equal to that of a like volume of water in other words, that the specific 
 heat of a solution is inversely proportional to its specific gravity. This 
 method of calculating may easily yield results several per cent, aside 
 from the truth with concentrated solutions. 
 
 Moreover, we find a general haziness concerning the question as to 
 whether the heat capacity of the factors or of the product of reaction is 
 to be used in the calculation. Should one multiply the temperature 
 rise by the heat capacity of the factors in order to obtain the heat evolved, 
 or is it the products which must be considered as having been raised 
 through the range of temperature in question? Only very recently has 
 this question been answered scientifically, and its answer is simply this: 
 either the one or the other may be used, provided that it is used intelli- 
 gently. When the heat capacity of the factors is used in calculating 
 the result, this result corresponds to the heat evolved by the reaction 
 occurring isothermally at the final temperature attained when the adiabatic 
 change is completed, whatever that may be. On the other hand, when the 
 
1278 GENERAL, PHYSICAL AND INORGANIC. 
 
 heat capacity of the products is used, the result corresponds to the heat of 
 isothermal reaction at the initial temperature. When there is no change 
 of heat capacity during the reaction, the results of the two methods 
 will, of course, be identical. In other words, in this last case the heat 
 evolved will be independent of the temperature at which the reaction 
 takes place, according to the well-known thermodynamic rule of Kirch- 
 hoff. 1 
 
 Further uncertainty concerning heat capacity arises from the fact that 
 the specific heat of the standard substance, water, changes with the 
 temperature and that therefore no expression for heat capacity is definitely 
 fixed without a qualifying phrase. In order to overcome this disadvan- 
 tage a proposition of Ostwald's to use the absolute C. G. S. scale has been 
 revived and a convenient standard of heat capacity, namely the capacity 
 raised one centigrade degree by one joule of energy, has been chosen. 
 This unit fixes the dimension of heat capacity much more definitely than 
 the old uncertain and changing one. Out of respect to the memory of 
 one of the founders of the first law of energy, the name "mayer" has been 
 suggested for this unit and its introduction seems to afford help in teach- 
 ing as well as to add precision to scientific statement. 2 
 
 In the coming revision of thermochemical data all the early incomplete- 
 nesses in these respects will be eradicated, and the matter will be put 
 upon the best basis possible to-day. 
 
 What now are the chief errors of calorimetry, which affect both the 
 determination of specific heat and of reaction heat? 
 
 Any one with any calorimetric experience whatsoever will recognize 
 that the greatest cause of uncertainty in results of this kind is the cooling 
 effect of the surroundings of the calorimeter. The errors of thermometric 
 reading, of the lag of the thermometer behind the temperature of the 
 surrounding medium, and all other uncertainties are trifling compared 
 with this. Therefore precise calorimetry is largely a question of properly 
 correcting for this cause of uncertainty, or else avoiding it altogether. 
 The well-known methods of Rumford and of Regnault as amplified by 
 Pfaundler, serve to a certain extent to correct for the effect of the ex- 
 change of heat with the environment. But the former, although it has 
 been much used in thermochemical work, is greatly at fault; and the latter, 
 although far better, is still imperfect. Rumford started his determination 
 as much below the temperature of the air around as he finished above 
 this temperature, supposing that the intake of heat during the first part 
 of the operation would balance the outgo during the latter part. We 
 have been able to show that this is by no means the case at any rate 
 in a vessel containing a solution and enclosed in a jacket of definite tem- 
 perature. Hence Rumford's method is not a very close approximation. 
 The Regnault-Pfaundler method depends upon Newton's law of cooling, 
 which under certain circumstances has been shown to be fairly accurate. 
 We must remember, however, that the cooling of the vessel is due to 
 convection and conduction as well as to radiation, so that the exact 
 fulfilment of Newton's law is hardly to be expected. Moreover the 
 evaluation of the rate of cooling depends upon the taking of a number 
 of thermometric readings which are "caught on the wing," as it were, 
 while the thermometer is moving. Hence, although the Regnault- 
 
 1 Richards, THIS JOURNAL, 25, 209 (1903). 
 1 Proc. Amer. Acad., 36, 327 (1901). 
 
RECENT INVESTIGATIONS IN THERMOCHEMISTRY. 1279 
 
 Pfaundler method may serve with sufficient approximation for quick 
 reactions, it still leaves much uncertainty in reactions which extend over 
 many minutes ; and even in quick reactions the lag of the cooling correction 
 may introduce some error. Further, many fundamental processes are 
 slow; and among them must be catalogued the determination of specific 
 heat, or heat capacity, because considerable time is needed as a rule to 
 communicate the heat to the substance to be studied. 
 
 It was with a view to eliminating these disadvantages that there has 
 recently been put into practice at Harvard a method of calorimetry 
 which wholly eliminates the correction for cooling by causing the tem- 
 perature of the environment around the calorimeter to change at the 
 same rate as the calorimeter itself. It is surprising that this obvious 
 and easily carried out device had not been applied before. It had, indeed, 
 been suggested by S. W. Holman 1 in 1895, although this paper was un- 
 known to me at the time of the first Harvard work. The somewhat 
 similar device used in the respiration calorimeter of Atwater and Benedict, 
 suggested perhaps even before this, is not exactly comparable. In the 
 respiration calorimeter the environment is not essentially changed in 
 temperature. It is merely kept constant, as is also that of the calorim- 
 eter, by a suitable quantitative cooling device. Hence, so far as I am 
 aware, the Harvard device was the first one in which the surroundings 
 of the calorimeter were changed in temperature by any considerable 
 amount during the progress of the experiment. 
 
 If the surrounding jacket about a calorimeter is thus changed in tem- 
 perature at exactly the same rate as the temperature of the calorimeter 
 itself, it is obvious that the calorimeter will neither gain nor lose heat 
 from its equally hot surroundings, excepting for the negligible quantity 
 of heat required to warm the small quantity of air immediately in contact 
 with it inside the jacket. Thus a calorimetric reaction may be made 
 really adiabatic. 
 
 Obviously there are several ways in which the outside water jacket in 
 a calorimeter might be heated in order to accomplish this purpose. The 
 simple device of pouring in hot water might be employed, or the water 
 might be warmed by an electrically heated resistance coil, or the jacket 
 itself might be made the scene of a chemical reaction of the same speed 
 and thermal intensity as that within the calorimeter itself. 
 
 Of these and other methods which suggested themselves the last named 
 seemed the most convenient and suitable for a chemical laboratory. 
 It has the special advantages that before the beginning of operations 
 all the apparatus and material employed may be at the temperature of 
 the room; that the maximum temperature attained may be easily cal- 
 culated with great nicety; that no point in the system can ever exceed 
 this maximum temperature, if the reaction is suitably chosen; and that 
 the speed of the reaction may be simply regulated by a stop cock ad- 
 mitting one of the reacting substances. A reaction easily regulated 
 and well suited to this purpose, namely, the neutralization of an alkali 
 with an acid, was chosen for this purpose. 
 
 The form of apparatus originally devised consisted of a lower jacket 
 
 containing alkali and a separate movable lid. More recently we have 
 
 found it convenient to enclose the calorimeter wholly in a water-tight 
 
 vessel a sort of submarine, provided with suitable conning towers or 
 
 1 Proc. Am. Acad., 31, 252 (1895). 
 
1280 GENERAL, PHYSICAL AND INORGANIC. 
 
 periscopes. 1 This water-tight compartment is wholly immersed in the 
 alkali to which is added, little by little, sulphuric acid in order to keep 
 the bath precisely at the same temperature as the interior, however 
 much this may be changed. Violent agitation of the warming alkali 
 is necessary in order that the heat may be quickly distributed throughout 
 the whole mass, and the interior of the calorimeter must be agitated also 
 more energetically than has usually been the custom, if great precision is 
 needed. In passing, I may state that we have evidence showing that 
 in the past no one has stirred his calorimeter violently enough. The 
 burettes delivering the sulphuric acid into the alkaline environment 
 are graduated in tenths of degrees, instead of in cubic centimeters, so 
 that a small deficiency in temperature may be instantly corrected with a 
 minimum of mental arithmetic. 
 
 This form of chemical calorimeter serves not only to determine with great 
 accuracy specific heats, but also to estimate the thermal output of all 
 forms of chemical reactions. With it series of determinations of many 
 kinds are in progress. 
 
 In the first place let me describe somewhat more closely the determina- 
 tion of specific heat with this apparatus, because upon this determination 
 the calculation of all other thermochemical results must depend. Within 
 the platinum calorimeter, enclosed in its submarine, is immersed a small 
 platinum bottle; and inside of this bottle a carefully measured chemical 
 reaction is allowed to take place which communicates its heat to the 
 calorimeter. By placing in the calorimeter, in the first place water, 
 and in the next place the unknown liquid whose specific heat is to be 
 determined, and each time allowing the measured reaction to occur 
 within the innermost platinum bottle, a direct comparison of the specific 
 heats of the standard and the unknown liquid is obtained. As the results 
 agree within one-twentieth of one per cent., the average of many experi- 
 ments must be much nearer than this, and it is not unreasonable to be- 
 lieve that the results thus obtained are at least five times as accurate as 
 those of Thomson or Marignac. 
 
 Having used this device and method for determining the specific heats 
 of liquids, it is now possible to proceed with the more accurate evaluation 
 of reactions in which liquids take part. In two recent investigations 
 the heats of neutralization of the acids and alkalis on the one hand and 
 the heats of solution of metals in acids on the other hand have been studied. 
 Time does not permit the detailed statement of the various precautions 
 necessary in these determinations. The former problem is of special 
 interest because of its relation to the theory of electrolytic dissociation, 
 and our revision of this work was prompted by the desire to discover the 
 extent of the deviation of the several results for strong acids from the 
 constant value, 137 calories or 57 kilo joules. Several unexpected points 
 were brought out in the investigation, the most important being the 
 irregularities in the results produced by the unequal distribution in heat 
 during mixing and also the grave errors caused in previous results by the 
 presence of carbonate in the alkali. The investigation is not yet finished, 
 but has already shown that many of the accepted results are much in 
 error even for this simple process of neutralizing an acid by an alkali. 
 
 The heats of solution of metals in acids are among the most essential 
 
 1 A device of this kind was employed by Richards and Forbes, Publications of the 
 Carnegie Inst., 56, 52 (1906). 
 
RECENT INVESTIGATIONS IN THERMOCHEMISTRY. 1 28 1 
 
 and fundamental of thermochemical data. The heats of formation of 
 all the metallic compounds depend upon them, because through them 
 the heat values are referred back to the element. Hence it is highly 
 important for exactness in thermochemistry that these values be deter- 
 mined vrith great precision. 
 
 As a matter of fact, in the past certain difficulties have interfered with 
 the perfection of the measurements. First and foremost among these 
 is the fact that the heat of solution of a metal requires much time, and 
 therefore the always somewhat uncertain correction for cooling in the 
 usual method becomes a serious fraction of the whole rise of temperature. 
 In the second place, the method generally used namely, the plunging 
 of a weigied sheet of metal into acid, and then withdrawing it, checking 
 the reactbn as soon as possible, and determining the amount dissolved 
 by loss k weight is open to serious criticism. It is impossible that 
 the withdrawal should be so quick as to introduce no error in the result. 
 
 The new method of adiabatic calorimetry, recently used at Harvard, 
 seems to b; especially suitable for such cases as this. With it cadmium, 
 zinc, magresium, aluminium and iron have already been investigated, 
 and very concordant and satisfactory results have been obtained. Here 
 again much greater purity of material than has been usual in work of 
 this sort wa; sought, and the results justify the trouble thus taken. There 
 can be no dcubt that in these cases also the older work was defective. 
 
 The heats of combustion of organic substances form another very im- 
 portant fiek for thermochemical research. These reactions carried 
 out in the cdorimetric bomb of Berthelot seemed especially suitable for 
 the application of the new method of calorimetry, and formed indeed 
 one of the first series of experiments to which it was applied. The com- 
 bustion of sold substances such as sugar presents no difficulty and imagi- 
 nation can easily picture the way in which this process might be carried 
 out in an aciabatic calorimeter. Several long series of experiments 
 with typical sibstances of this sort have been made in order to test the 
 method, with satisfactory results. * The combustion of liquids is a more 
 difficult probhm. As you well know, Thomsen endeavored to burn 
 liquids by firs; vaporizing them with the help of electrically generated 
 heat in his socalled "universal burner." We now know that some of 
 the superfluous heat from the electric coil must have found its way into 
 the calorimete", so that these results are usually too high. Berthelot 
 and Stohmann on the other hand, determined the heat of combustion 
 of organic liquids by saturating cellulose with the liquid, which was then 
 ignited in the lomb. This latter method of procedure is evidently open 
 to the error catsed by a varying loss of the organic liquid by evaporation. 
 Not all the vaoor of the organic liquid spread throughout the bomb is 
 capable of beirg burnt, hence Berthelot's results for volatile liquids are 
 probably all t>o low. The truth would be expected to lie somewhere 
 between them Thomsen's results for the more volatile liquids being prob- 
 ably the more accurate because there the accidental heating from his 
 apparatus was unimportant, and Berthelot's results for the less volatile 
 liquids being better because there the loss through evaporation would 
 cause less error. 
 
 We sought to overcome these difficulties by enclosing the organic liquid 
 in a small, /ery thin glass bulb, flattened on the sides and completely 
 
 1 Proc. Aner. Acad., 42, 573 (1907). 
 
1282 GENERAL, PHYSICAL AND INORGANIC. 
 
 full of liquid. No difficulty is found in making such bulbs, and they 
 will stand several hundred atmospheres of pressure without bursting, 
 if completely full of liquid, because the glass of the flattened sides is suffi- 
 ciently flexible to permit of considerable compression. These closed glass 
 bulbs were put inside the bomb in a very small platinum crucible, and 
 upon a thin glass shelf above them was placed a small weighed quantity 
 of powdered sugar. The sugar was ignited first in the usual way. This 
 exploded the bulb and instantly lighted the vapor of the liquid at all 
 points so that none escaped combustion. In this way we have been able 
 to show that the heat of combustion of volatile organic liquids is as a 
 rule distinctly higher than Stohmann and Berthelot supposed ft to be. 
 We have unquestionable evidence that complete combustion of their 
 vapor has at last been attained. These methods open the way to an un- 
 limited amount of further experimentation, and promise to afford results 
 upon which interesting theoretical considerations may be founded. 
 
 It is a pleasure to acknowledge my thanks to my several assistants, Pro- 
 fessor A. B. Lamb, and Drs. L. J. Henderson, G. S. Forbes, H. I/. Frevert, 
 A. W. Rowe, R. H. Jesse, Jr., and L. L. Burgess for their expert assistance 
 in these protracted and often tiresome researches, as well as to express my 
 obligations to the Cyrus M. Warren Fund of Harvard University, the 
 Rumford Fund of the American Academy of Arts and Science and espe- 
 cially to the Carnegie Institution of Washington, for generois pecuniary 
 help in the prosecution of the work. 
 
 Before closing let me review briefly the recent advance! in thermo- 
 chemistry which I have attempted to enumerate. In the first place, 
 the thermometric scale has been far more definitely fixed than it was 
 thirty years ago. In the next place, the determination of specific heat 
 and therefore of heat capacity has been put upon a scienlffic basis and 
 its precise treatment in the calculation of thermochemical results has been 
 pointed out. In the next place the most serious correction tor all thermo- 
 chemical results in the past, namely the cooling correction has been en- 
 tirely obviated by the use of the method preventing loss of my heat from 
 the calorimeter by enclosing the latter in a jacket of similarly changing 
 temperature. Again the necessity for more active agitatim of the con- 
 tents of the calorimeter has been demonstrated, and the necessity of the 
 use of very pure materials has been put beyond question. In every case 
 the effort has been made to insure the completeness of tte reaction and 
 to correct for any side reactions which may take place at the same time, 
 so that the final results may represent truly the data sought. In short 
 the effort has been made to apply to these fundamental figtres concerning 
 chemical energetics the same kind of precision which has recently been 
 attempted in the revision of atomic weights; and although on account 
 of the greater complexity of the problem the percentage accuracy thus 
 far reached has probably not equaled that in the case of atomic weights, 
 one cannot help thinking that the proportional gain ovei the previous 
 investigations is perhaps as great in this case as in the other. 
 
 HARVARD UNIVERSITY, CAMBRIDGE, MASS. 
 
MOLECULAR REARRANGEMENTS. 1 
 
 BY WILLIAM A. NOYES. 
 Received September 16, 1909. 
 
 "The end of chemistry is its theory. The guide in chemical research 
 is a theory" (Phil. Mag. [4], 16, 104 (1858)). With these words A. S. 
 Couper began one of the most remarkable papers in the history of chem- 
 istry. At the time when he wrote the system of types advocated by 
 Gerhardt had come into very general favor. Chemists were busy arrang- 
 ing the compounds of carbon and of other elements as well, in classes 
 according to a few simple types, especially in accordance with the type 
 of water and its multiples. The advantages of the system in comparison 
 with what had gone before were very evident and organic chemistry 
 was making rapid progress with its aid. It answered very well for the 
 classification of many of the compounds then known and as a guide in 
 the discovery of a great many new ones. And most of the chemists of 
 that day, as always, were satisfied in working away at the discovery of a 
 vast array of new facts and marshaling these in accordance with a highly 
 mechanical theory with very little thought about its philosophical basis. 
 
 Under these conditions two master spirits, Couper and Kekul, suc- 
 ceeded, entirely independently, in grasping those simple principles which 
 lie at the foundation of our knowledge of the structure of compounds 
 of carbon. Only as the result of an unfortunate accident was Kekul's 
 paper published before that of Couper. 
 
 It is interesting, and I think profitable, for us to recall that it was 
 chiefly a consideration of the philosophical basis for Gerhardt's system 
 which led Couper to reject it and propose something better. In criticizing 
 the system he says of Gerhardt "He is led, not to explain bodies according 
 to their composition and inherent properties, but to think it necessary 
 to restrict chemical science to the arrangement of bodies according to 
 their decomposition, and to deny the possibility of our comprehending their 
 molecular constitution. Can such a view tend to the advancement of 
 science? Would it not be only rational, in accepting this veto to renounce 
 chemical research altogether?" 
 
 I have dwelt thus on Couper's point of view because it carries with 
 it, as it seems to me, a lesson which we chemists of to-day may well take 
 to heart. Very few are gifted with the insight of a Dalton, a Faraday, 
 a Couper or a Rutherford but when a glimpse of the real things which 
 lie beneath the phenomena which we observe comes to such an one it 
 may, guide the development of science for a decade, for a century, or 
 even, if sufficiently true, for all time. And it seems possible that if we 
 directed our thoughts more toward fundamental problems instead of 
 towards the accumulation of compounds and of facts which are little 
 more than permutations of compounds and facts already known, more 
 real progress could be made. 
 
 The new principles proposed by Couper were very simple: First, that 
 atoms show "degrees of affinity" or as we should call it, valence, and 
 second, that carbon atoms can combine with each other. But these two 
 simple principles have been the foundation on which chemists have built 
 a knowledge of the structure of one hundred thousand compounds of 
 1 An address delivered at Worcester, Mass., September 14, 1909, at the celebra- 
 tion of the twentieth anniversary of Clark University. 
 
1369 MOLECULAR REARRANGEMENTS. 
 
 carbon. These principles involve a knowledge of the actual arrangement 
 of atoms within the molecule in the sense of the order of their successive 
 attachments to each other. Thus far, at least, they are accepted by all 
 active workers in organic chemistry and there is, among these, a prac- 
 tically universal belief that atoms and molecules actually exist and that 
 there is something in the structure of the molecules which actually cor- 
 responds to our formulas. The two principles just stated have been 
 further extended, especially by the study of optically active and of cyclic 
 compounds to include still more definite ideas with regard to the actual 
 arrangement of atoms in space and this development of stereochemistry 
 has also received very general, though not quite universal, acceptance. 
 
 For a clearer understanding of molecular rearrangements we are in 
 need of more definite knowledge with regard to the nature of those in- 
 teratomic forces or attractions which hold atoms together in molecules 
 and which also cause atoms of different molecules to react with each 
 other. Many theories with regard to these forces have been proposed 
 but none has, as yet, received any very general acceptance and the majority 
 of chemists feel that any satisfactory knowledge of this sort is beyond 
 our reach. But in 1858 nearly all chemists believed that any definite 
 knowledge of the arrangement of atoms in chemical compounds was 
 impossible, yet all of the facts for the acquirement of such knowledge 
 were already in their hands and it only needed a clear statement of the 
 simple principles proposed by Couper and by Kekule" and the application 
 of those principles in the explanation of facts already known to make 
 clear the structure of a large number of substances. Is it not possible 
 that the answer to other, equally fundamental questions lies at our hands 
 to-day? 
 
 It is in the hope that this may be so that I shall venture to state some 
 of these fundamental questions as they present themselves to me. 
 
 The first of these is as to the nature of the attractive forces between 
 atoms. The question is, perhaps, bound up with that of the nature of 
 attraction between material bodies in general and may be equally far from 
 a solution. Newton seems to have assumed an attractive force as an 
 inherent property of matter and most of the discussion of atomic forces 
 starts with a similar tacit assumption. But, as soon as the question is 
 raised the mind revolts against the assumption of a force exerted through 
 space without a medium. Physics has abandoned any idea of inherent 
 attractive or repulsive forces in sound, light, heat or electricity and has 
 accepted a kinetic explanation instead. Is it not probable that we must 
 ultimately do the same for atomic forces? The discoveries in connection 
 with radium have made us familiar with the notion that the atoms are 
 very complex in their structure and that their parts may possess an almost 
 inconceivable amount of kinetic energy. The spectroscope long ago 
 demonstrated to us that such an atom as that of iron can send out im- 
 pulses through the ether similar in complexity to those impulses of sound 
 which come from a whole orchestra. It seems altogether probable that 
 these impulses come from motions within the atom and not from vibra- 
 tions of the atom as a whole. If we think of such intraatomic motions 
 as general and that such motions within the atoms may produce effects 
 which are transmitted through the ether, a kinetic explanation of atomic 
 and molecular attraction seems possible. 
 
 The second question with regard to the atomic forces is whether these 
 
 10 
 
ORGANIC AND BIOLOGICAL. 1370 
 
 forces are purely attractive, resembling gravitation, or polar, partly 
 attractive and partly repulsive, resembling or identical with electrical 
 forces. You are all familiar with the fluctuation of opinion on this point. 
 During the first half of the nineteenth century chemists came gradually 
 to a pretty general agreement that the atomic forces are electrical in their 
 nature. Then came the discovery of the substitution of chlorine for hy- 
 drogen in organic compounds and the overthrow of the old dualistic, 
 electrochemical theory. Then for several decades the question of any 
 connection between electrical and atomic forces was generally ignored 
 and the attractions of the atoms were considered as direct and positive, 
 though, of course, specific in character. During the last twenty years, 
 as the theory of Arrhenius with regard to electrolytic dissociation or 
 ionization has come into quite general favor, many different writers have 
 proposed theories which identify atomic attractions with electrical forces. 
 Faraday's law and the whole group of phenomena which find their most 
 satisfactory explanation in the theory of ionization point very strongly 
 toward an intimate relation between the two in the case of electrolytes. 
 But if we assume that the forces which hold atoms together in electrolytes 
 are electrical it is difficult to escape from the conclusion that the forces 
 are electrical in the molecules of non-electrolytes also, for the two classes 
 pass over into each other so gradually that it is very hard to believe that 
 after the line is passed we are dealing with a radically different kind of 
 atomic force. Further than this, an electrolyte may be formed in many 
 cases by two different processes, by double decomposition in solution and 
 by the direct union of the elements. Hydrochloric acid, acetylene and 
 probably methane (from zinc methyl and by direct union of carbon and 
 hydrogen) may be cited as illustrations. The nature of the compounds 
 does not seem to depend at all on whether they are formed by the one 
 process or by the other. 
 
 The idea that organic reactions are all ionic in character enables us, 
 also to understand many reactions not so easily understood otherwise. 
 Thus ethyl alcohol gives with phosphorus pentachloride, chlorethane, 
 while phenol gives with the same reagent partly chlorobenzene, partly 
 phenyl phosphate. If we assume, as seems natural, that ethyl alcohol 
 ionizes to ethyl and hydroxyl while phenol ionizes partly in the same 
 way but chiefly to hydrogen and phenoxy ions these reactions become 
 clear : 
 
 4 C 2 H 5 + + 3 OH- + +H++P+++++ + 5C1- = 4 C 2 H 5 C1 + H S P 
 or 
 
 4C 2 H 5 ++ 4 OH- + PC1++++ + 4C1- = 4 C 2 H 5 C1 + PC1(OH) 4 
 PC1(OH) 4 = H 3 PO 4 + HC1 
 
 3 C 6 H 5 0- + 3 H+ + C 6 H 5 + + O + H+ + P+++++ + 5C1- = 
 
 C 6 H 5 C1+(C 6 H 5 ) 3 P0 4 + 4 HC1. 
 
 If we accept the reasons given and identify atomic and electrical forces 
 we have still the question as to the real nature of these forces, for after 
 we have called them electrical and even after we have identified them, 
 perhaps, as residing in electrons (Faraday's law and many other things 
 point that way) we still have the inherent difficulty of conceiving an at- 
 traction existing between bodies at a distance without a medium and I 
 can not help a strong belief that we must ultimately have a theory for 
 the attractions as an effect produced by the motions of the electrons. 
 
 ii 
 
137 1 MOLECULAR REARRANGEMENTS. 
 
 Such a belief need not interfere with our use of the idea of positive and 
 negative charges as a convenient present hypothesis. It may, perhaps, 
 help us to a theory with regard to a reversal of the charge which it seems 
 necessary to assume in certain cases and which has led to Abegg's theory of 
 normal and contravalences. The hypothesis proposed by J. J. Thompson 1 
 that combination is caused by the transfer of negative corpuscles from 
 one atom to another has much in its favor but it assumes inherent at- 
 tractions between negative corpuscles and positive atoms or parts of 
 atoms. Although the distances are small such attractions are in as 
 much need of further explanation as is the force of gravity. We assume 
 that the attractions and repulsions between conductors conveying currents 
 or between magnets are due to motions in the ether between them. Is it 
 not possible that the attractions and repulsions between corpuscles and 
 atoms amy be explained in a similar manner? 
 
 The third and last question which I wish to raise is as to the nature of 
 the forces which atoms already combined with other atoms exert in the 
 attraction or repulsion of still other atoms. Are these residual forces 
 merely the same forces which hold the atoms in combination still acting 
 past those atoms which are nearest and upon others further away or are 
 they different forces as seems to be implied rather indefinitely in the 
 "partial valences" of Thiele? The former idea seems simpler and more 
 logical. This question is intimately associated with the mechanism of chem- 
 ical reactions, the causes for the stability or instability of compounds and 
 especially with questions of molecular rearrangements. As illustrations 
 of facts requiring an explanation by a more intimate knowledge of forces 
 of this sort we may cite the stability of the union of carbon with carbon 
 in ethane as compared with oxalic acid, in propionic and butyric as com- 
 pared with malonic and acetoacetic acids and in the esters of these acids 
 as compared with the free acids, in benzoic acid as compared with 2,6- 
 dimethyl-4-aminobenzoic acid (Am. Chem. J., 20, 813 (1898)) in hydro- 
 cinnamic as compared with phenyl propiolic acid and in acetic as compared 
 with trichloracetic acid. The instability of compounds similar to those 
 mentioned has long been accepted as an empirical fact and it is easy to 
 predict many cases where such instability will occur but the reason for 
 the instability has scarcely been discussed. With one exception the 
 separation always occurs between two carbon atoms, one, at least, of 
 which is united to a group or atom commonly designated as negative; 
 and the exception may be only apparent, for the decomposition of 2,6- 
 dimethyl-4-aminobenzoic acid takes place in an acid solution in which 
 the amino group is combined with hydrochloric acid and may be con- 
 sidered negative. 
 
 It is very noticeable that acetoacetic acid, CH 3 COCH 2 CO 2 H, is much 
 less stable than pyrotartaric acid, CH 3 COCO 2 H. This is some slight 
 indication that the separation of the carbon atoms is ionic in character, 
 taking place more readily when there is a greater contrast between the 
 atoms united together. It may be that, in this connection, we have 
 
 1 "The Corpuscular Theory of Matter," p. 126. See also the recent discussion by 
 Falk, School 0} Mines Quarterly, 30, 179 (1909). My own discussion of the reaction 
 between chlorine and ammonia, THIS JOURNAL, 23, 460(1901), also has an important 
 bearing on Thompson's hypothesis of the transfer of electrons in the union of atoms of 
 the same element, Loc. cit., p. 127. 
 
 12 
 
ORGANIC AND BIOLOGICAL,. 
 
 1372 
 
 not sufficiently considered the difference between stability and reactivity. 
 Thus sodium chloride and sodium nitrate are both instantaneously re- 
 active in solutions, separating between the sodium and the chlorine or 
 the sodium and the nitrate group but when heated the former compound 
 is extremely stable while the latter decomposes between the nitrogen 
 and oxygen rather than between the sodium and the nitrate group. 
 
 This leads me to the consideration of some of those molecular rearrange- 
 ments in which I have been especially interested. When camphor is 
 heated with phosphorus pentoxide it gives cymene. 
 
 CH, 
 
 CH, 
 
 -CO 
 
 CH 3 C CH 3 
 
 CH, 
 
 -CH- 
 
 -CH, 
 
 CH 3 
 
 CH C CH 
 
 II I 
 
 CH C = CH 
 
 CH 3 CH CH 3 
 
 H,O. 
 
 The two carbon atoms which separate from each other in this rearrange- 
 ment bear the same relation to the carbonyl group as do the two carbon 
 atoms which separate in either the acid or ketonic decomposition of 
 acetoacetic ester. This primary separation of carbon from carbon is fol- 
 lowed by the wandering of four hydrogen atoms, two of these leaving 
 the molecule entirely with the oxygen. 
 
 When camphor is heated with sulphuric acid it undergoes a different 
 rearrangement, giving -acetyl-o-xylene (Armstrong and Kipping, /. 
 Chem. Soc., 63, 81). 
 
 CH, 
 
 CH 
 
 CH 2 - 
 
 CH, 
 
 -c- 
 
 -CO 
 
 CH, 
 
 CH, 
 
 -CH- 
 
 -CH 2 
 
 CH 
 
 CH 
 
 II 
 C-CH, 
 
 C CH, 
 
 4 H. 
 
 Here the rearrangement is much more complex and we must assume 
 two primary separations of carbon atoms, both of which are again in the 
 same relation as before to the carbonyl group. We have then a different 
 carbon atom uniting with one of those which has separated, forming a 
 six- ring and a transfer of a methyl group from one carbon atom to another, 
 a transfer that has been noticed so many times in other compounds that 
 it can no longer be considered abnormal. Four hydrogen atoms are lost 
 but it is not necessary to consider that more than one hydrogen atom 
 has wandered within the molecule. 
 
 When either dihydrohydroxycampholytic acid or a-campholytic acid 
 is allowed to stand for a short time with dilute sulphuric acid (i : i) 
 it is transformed into /?-campholytic acid. 
 
 CH, 
 
 -C CH 3 
 
 II 
 CH 
 
 CO 2 H CH CH 2 
 a-Campholytic acid. 
 
 CO 2 H- 
 
 j9-Campholytic acid. 
 
1373 
 
 MOLECULAR REARRANGEMENTS. 
 
 If /3-campholytic acid is allowed to stand with concentrated hydro- 
 bromic acid it passes back to the hydrobromide of d/-a-campholytic 
 
 acid : 
 
 / 
 
 CH 8 
 CH 
 
 CO,H C- 
 
 CH 2 
 -CH, 
 
 Vxiio\ 
 
 >< 
 
 CH/ 
 CO 2 H ( 
 
 /CH 3 
 
 v Q/ 
 
 CH 2 
 ^H CH 2 
 
 /?-Campholytic acid. dZ-Hydrobromide of a-<5ampholytic acid. 
 
 The latter compound may lose hydrobromic acid and give dl-a-cam- 
 pholytic acid, or it may exchange its bromine for hydroxyl giving dl-a- 
 hydroxydihydrocampholytic acid (Walker and Cormack, /. Chem. Soc., 
 77, 380; Noyes and Blanchard, Am. Chem. J., 36, 285 ; Noyes and Patterson, 
 Ibid., 27, 426). 
 
 In both of these transformations the methyl group separates from a 
 carbon atom adjacent to a carbon atom which is doubly united to a third, 
 just as in the acetoacetic ester the separation is from a carbon atom adjacent 
 to one which is doubly united to oxygen. A similar relation, but with 
 some variation is found in the transformation of the nitroso derivative 
 of the anhydroaminolauronic acid to laurolene (Noyes and Derick, /. Am. 
 Soc., 31,669(1909)). 
 
 CH 3 CH, 
 
 ^C 
 
 CH, O 
 
 CH 2 . 
 
 H 
 
 HNO 
 
 CH 8 CH CH 3 
 
 Here the carbonyl group leaves (as carbon dioxide) a carbon atom 
 attached to another which is united only to carbon. Doubtless the 
 vibrations set up in the molecule at the moment of decomposition are an 
 important factor in this rearrangement. 
 
 The pinacone-pinacolin rearrangement is, perhaps, the first of this 
 type which was studied. 
 
 OH 
 
 CH,\ 
 
 5i CH 3 ^c co CH S . 
 
 CH/ 
 
 Tiffeneau and his collaborators have recently studied very many re- 
 arrangements similar to these, phenyl and other groups as well as methyl 
 being transferred in many cases. 
 
 These shiftings of groups seem to take away from under us one of the 
 most important principles on which we rely for the determination of 
 structure, the principle that groups of atoms pass from one compound 
 to another without changing their mutual relations. But when we think 
 of the matter a little further we see that in all chemical reactions we 
 expect the atoms to separate from each other at some point, and the only 
 thing which surprises us is that a separation has taken place at a point 
 
ORGANIC AND BIOLOGICAL. 1374 
 
 where we did not expect it. We can already see some empirical relations 
 between the compounds in which these separations and rearrangements 
 take place and can predict to a certain extent where they are liable to 
 occur. But we are still wholly in the dark as to the real forces which 
 lie behind and are the cause of the transformations. 
 
 J. J. Thomson, Rutherford and others have shown that in the phe- 
 nomena of conductivity of gases and of radioactivity we have new and 
 most powerful means of studying the properties of matter and energy 
 which have thrown a flood of light upon the nature of atoms. Ostwald 
 at the other extreme has wished to discard atoms altogether and to explain 
 structural organic chemistry on the basis of thermodynamics. Richards, 
 from a somewhat intermediate point of view but with distinctly more 
 sympathy with Ostwald than with Thomson, has given us a conception of 
 compressible atoms which is surprisingly like the latter's corpuscular theory 
 of chemical combination as developed in his latest book. Michael wishes 
 to explain phenomena of this sort by the law of entropy. Thiele, imbued 
 with the ideas of structure, explains them in part by partial valences. 
 Still others have attempted to study such problems from the properties 
 of crystals, the absorption of light, and a great variety of other phenomena. 
 The great number of properties which must finally be coordinated in 
 any true explanation of atomic and molecular forces is discouraging and 
 gives some basis for that agnostic point of view which considers the 
 number of possibilities infinite and that we can never hope for a knowl- 
 edge of the truth even as to the existence of atoms. Let us rather take 
 the more hopeful view that some one, in a not too distant future, will 
 give us a simple and comprehensive theory of the nature of atoms and of 
 the forces which bind them together in compounds. The one who is 
 to do this must not look at science as cut up into water-tight compart- 
 ments but must be able to coordinate the evidence which conies from 
 workers in many diverse fields of chemistry, of physics and of other 
 sciences. 
 
 URBANA, ILL. 
 
ORGANIZATION OF INDUSTRIAL RESEARCH. 1 
 
 BY WILLIS R. WHITNEY. 
 Received November 6, 1909. 
 
 The intimate connection between the purely scientific research of a 
 people and its advance in the art of good living cannot be too frequently 
 discussed. The organization of industrial research involves arranging 
 and maintaining a body of involute parts as an operative whole of high- 
 est efficiency. It is never perfectly accomplished, and the fact that 
 improvement can always be made is an incentive for its discussion. 
 
 A recent copy of Life has this to say, which, without straining, bears 
 direct upon industrial research: 
 
 "This is the most interesting country in the world. The game here 
 is the biggest that is being anywhere played. The problems of humanity 
 that are being worked out here are the greatest problems under considera- 
 tion, and the prospect of solving them is better than it is anywhere else." 
 
 Lord Bacon said: "The real and legitimate goal of the sciences is the 
 endowment of human life with new invention and riches." He, in turn, 
 cited King Solomon, who said, "it is the glory of God to conceal a thing, 
 but the glory of a king to search it out." 
 
 Bacon distinguishes three degrees of ambition: 
 
 First, that of men anxious to enlarge their own power in their own coun- 
 try. This is "vulgar and degenerate." 
 
 Second, that of men who strive to enlarge the power and empire of 
 their country over mankind. This is "more dignified, but not less covet- 
 ous." 
 
 Third, that of those who strive to enlarge the power and empire of 
 mankind in general over the universe. Evidently this is the best, and 
 is the real ambition, whether recognized or not by himself, of any good 
 experimenter. 
 
 For purposes of systematic analysis, the subject, "Organization of In- 
 dustrial Research," may be divided into two parts: 
 
 Part one, the personal or mental organization, with its requirements, 
 etc. 
 
 Part two, the objective or material organization. 
 
 For brevity, these may be called the mind and the matter organiza- 
 tions. 
 
 The former, or personal, I will subdivide into such parts as: 
 
 Its training and characteristics. 
 
 Division of its labors. 
 
 Its records, etc. 
 
 The objective or matter organization, I divide into : 
 
 1 An address delivered at the Twentieth Anniversary of Clark University, 
 Worcester, Mass., Sept. 17, 1909. 
 
 16 
 
GENERAL, PHYSICAL AND INORGANIC. 72 
 
 The fields for material research. 
 
 The laboratory equipment and systems of its material co-operation. 
 
 Naturally, the personal comes first, relatively and chronologically, 
 and the mental precedes the material. The personal factor is everything 
 in industrial research. Strangely enough, it is everywhere and always 
 dominant, while every other factor is sometimes recessive. In an organ- 
 ization "A" cannot work well with "B" because one is too slow, too 
 fast, to egotistical, too jealous, too narrow, etc. Nowhere else do the 
 personal traits protrude so much as in concerted research. And so I 
 hold that above all, as an industrial experimenter, I should like as broad 
 a human training as possible, before any other specific one. This proba- 
 bly means little more than acquirement of a demonstrated desire to play 
 fair, and it may be no more applicable to this field than to others. 
 
 To one always in close touch with research, it seems as though there 
 is an immutable law of nature which may be stated as follows: (It is 
 an application of the principle of reversible reactions so as to include the 
 reactions of the mind.) 
 
 The equilibrium between mental and material conception is so sensi- 
 tive that anything which, to the fair mind, seems possible, is to the trained 
 persistence permissible. If this should be proven not strictly true, it 
 would still be a good working hypothesis for a research organization. 
 
 This theory requires, then, a certain characteristic in the generally 
 successful research operator. This is recognized in optimistic activity 
 and, to my mind, should be placed first among the requisites. It is placed 
 above knowledge, because, without it, little that is new will ever be done 
 except by accident. With active optimism, even in absence of more 
 than average knowledge, useful discoveries are almost sure to be made. 
 
 Speaking from personal analysis and from the observation of others, 
 I would say that general-chemical and physical knowledge may some- 
 times be as much a detriment as a help to one imbued only with a need 
 of solving new problems. A possible explanation is this: We always 
 reason deductively. We apply general laws in attempting to answer 
 specific questions. To any specific problem of research there are usually 
 general laws which may seem to forbid the solution. These laws are 
 known and revered. Naturally, the unknown, specific ways by which 
 it may be solved are more or less hidden. An illustration may not be 
 out of place here : 
 
 Cotton may be dissolved in a solution of zinc chloride. The solution 
 may be squirted through a die into alcohol in such a way that a smooth, 
 coagulated cellulose thread is thereby obtained. This may be heated 
 so as to give a solid, compact and pure carbon filament. Many are thus 
 made. But as a new problem, it would certainly appear quite imprac- 
 ticable to one who might have a fairly extensive knowledge of the chem- 
 istry of the materials. Generally speaking, zinc chloride solution does 
 not dissolve cellulose. Only a strong solution, kept at a high temperature 
 for a long time, will give the desired solution. In general, too, it could 
 not be squirted and coagulated into a smooth thread. Very specific 
 conditions are necessary. Finally, the treatment with gradually rising 
 temperature, which alone succeeds in giving the compact carbon fila- 
 ment, is a matter of specific detail. The places in this process where 
 general reasoning points to failure are numberless. Years of multiplied 
 effort are necessary to perfect such a process. Once established, it is 
 
 17 
 
73 ORGANIZATION OF INDUSTRIAL RESEARCH. 
 
 easily analyzed along the lines of understood reason and theories of re- 
 actions may be based upon the facts. But such processes are not laid 
 out greatly in advance of their accomplishment. The successful steps 
 are found among the many which are actually attempted, and something 
 more than general knowledge is necessary. This something is hopeful 
 pertinacity, optimistic activity. To a chemist imbued with fair knowl- 
 edge, it was recently apparently useless to attempt such an experiment 
 as the continual removal of traces of hydrogen from oxygen by passing 
 the gas through a red-hot iron pipe. He had seen iron wire burned 
 rapidly in oxygen, he tried wrought iron and the iron was oxidized, and 
 his knowledge was vindicated, but he also tried cast iron and found that 
 it did not burn and that it would operate perfectly. A scramble for an 
 explanation evolved the theory that the silicon burning to silica protected 
 the iron. Ex. postfacto theories are permissible. 
 
 As the mental world is constituted, optimists are greatly in the minority, 
 when one counts those only who are also imbued with knowledge. There- 
 fore, in practice, the optimist must be used to crystallize the efforts of 
 others less optimistic. Thus, any large industrial research laboratory 
 is soon perforce, systematized into organized clusters of people, working 
 along distinct and different lines. This permits, in our case, of the 
 combined use, to maximum efficiency, of the delicate hands of young 
 women, the strength and skill of trained mechanics, the mind of the use- 
 ful dreamer, the precision and knowledge of the skilful chemist, and the 
 data of the accurate electrical engineer. 
 
 Simple mathematical axioms make clear the fact that a group of opera- 
 tors working together on a subject, are related to the same group opera- 
 ting separately, as a power is related to a simple sum. This principle 
 holds as well among a group of groups and to related subjects. It is evi- 
 dent, for example, that knowledge gained along the line of insulation 
 would be of use in a study of conduction, and that the man who had 
 studied the reduction of tungstic oxide by carbon in vacua could help 
 the one who is working with a pressure furnace, upon the equilibrium 
 between carbon monoxide and carbon dioxide. Therefore, the strength 
 of a research department, properly operated, should rise exponentially 
 with its numbers. 
 
 To this audience, the importance of highest advance in specific chem- 
 ical and physical training will probably be apparent, but an expression 
 of it may be of use. The supply of highly trained men is below the de- 
 mand. There is a healthy supply of moderately trained men. This 
 applies to all general, scientific training. Let me give more concrete 
 ideas. There are a hundred chemists who can fill satisfactorily an analyst's 
 position, to one who knows what J. J. Thomson has done or who reads 
 Drude's Annalen. Reading the Annalen is not a "sine qua non," but it 
 is an indicator of no little merit. If a chemist or a physicist is not suffi- 
 ciently interested to keep informed, he is probably not going to work at 
 high efficiency as an investigator. This does not preclude the possibility 
 of splendid research work being done by some one who is confined to a 
 very limited field of vision, but such cases are the exception and cannot 
 be used as bases for common application. In general, the man with the 
 best tools and with the best knowledge and experience in their use, will 
 advance most rapidly in industrial research. In my own experience, 
 we frequently have a line of work which demands the addition to the 
 
 18 
 
GENERAL, PHYSICAL AND INORGANIC. 74 
 
 force of well trained men. The difficulty which stands out most mark- 
 edly when considering this problem is usually the scarcity of men who 
 are highly enough trained along the line of pure research. While in many 
 fields of industrial research new and brilliant discoveries will continue 
 to be made suddenly and, as it were, out of new cloth, still many more 
 are being made by the most careful application of highly refined methods 
 and knowledge, to processes which already seem at first pretty well worked 
 out. This intensive farming is most promising and demands the highest 
 skill. It is to-day most difficult to find American trained men who can 
 do this work. It is a German attribute which we would do well to make 
 our own. 
 
 If the chemist is only a chemist or the physicist confined to pure physics, 
 he is liable to overestimation of the laws he learns. He should be some- 
 thing of a "mental mixer," one who has enough history, enough psy- 
 chology, and enough faith to read possibility of acquirement for the future 
 out of knowledge of attainments in the past. 
 
 As we have said, one of the most practical detriments to successful 
 industrial research is that automatic action of the mind which recognizes 
 the possible grounds for a failure quicker than it sees the probable ways 
 to success. Research needs more aviators. Those of us who feel the 
 work-horse brand on our work have a call to cultivate a flying spirit, 
 and are to be condemned only if we stand still. 
 
 In this connection, I am in favor of anything which helps train the 
 American student in the path of sanguine research. It can be done Jay 
 research men themselves, but probably not by others. It is not the 
 knowledge which the student preparing for research needs, so much as the 
 spirit of the investigator. His thoughts should not be fettered by laws, 
 but helped by them to fly. This can be done best by those who are opti- 
 mistic almost to the extinction of reason. 
 
 A search in the research laboratories of the world to-day would dis- 
 close large numbers of J. J. Thomson men, Ostwald men, Nernst men, 
 van't Hoff men. The teacher probably made the school. The investi- 
 gator probably endowed the students, not with facts alone, but with 
 spirits. We are not of that hopeless class who assume that the sparks 
 of genius are only Heaven-sent, but we are inclined to adopt as an axiom 
 that man is flexible, auto-corrigible and mentally elastic beyond limit. 
 Therefore the rare genius in research, as elsewhere, is the one most given 
 to hopeful effort. 
 
 To dwell for a moment upon points in a system for co-operation of a 
 research force, I will describe our own scheme. 
 
 The present corps comprises about eighty people, about thirty of whom 
 are college men, mostly chemists. Every man or woman on the 
 research staff is expected to give undivided effort to the work. 
 Whatever invention results from his work becomes the property of 
 the company. I believe that no other way is practicable. An attempt 
 to reward systematically such labors by a scheme of royalty payment 
 is more impracticable than the operation of a manufacturing plant upon 
 a graded scheme of profit sharing. In this case an immediate and fairly 
 equitable division of profits is sometimes possible. In research, the 
 problem itself is an asset of the organization. Both the equipment 
 and the risks belong to the organization. The accumulated experience 
 of the force as a whole is its property. Finally, the privilege of direct- 
 
 19 
 
75 ORGANIZATION OF INDUSTRIAL RESEARCH. 
 
 ting the work of operators along lines where no direct financial benefit 
 (or an immeasurable one) to the company could ever be determined, 
 must belong to it. Every operator is expected to keep good notes and 
 his books become a part of the laboratory files. In most cases weekly 
 typewritten reports are made by each worker, and copies of these also 
 become part of accessible library files. For purposes of establish- 
 ment of dates, etc., witnesses who read and understand the notes also 
 endorse them. Photographs of apparatus, curves, etc., are frequently 
 added wherever useful, and each room of the laboratory is photographed 
 regularly and the dated photographs are bound in books, to record stand- 
 ing conditions. Wherever practicable, single sheets, of standard reporr 
 size, are printed to cover oft-repeating data, so that the experimenter 
 regularly fills in certain blanks, as, for example, in experiments on carbon 
 motor brushes: the composition of the particular lot, temperature and 
 time of drying and firing, hardness, resistivity, tensile strength, and all 
 other tests of the product. The use of plotted curves on standard milli- 
 meter paper, for use where one property of material is studied as a func- 
 tion of some other variable, is very common in our reports. This occurs, 
 for example, in practically all cases where electric furnace work is de- 
 scribed, and where the changes undergone by incandescent lamps during 
 their life are recorded. 
 
 These conditions are the result of eight years of development. The 
 system has been subjected to many changes and may still be greatly im- 
 proved. It is possible to have such a complex system of record that 
 efficiency is sacrificed. We have reached the present stage because of 
 frequent indications of previous weakness in the simpler methods. Very 
 few good investigators can keep good notes. The more interested the 
 investigator becomes, the more difficult it seems for him to carefully 
 record his passing work. His eyes and mind are always upon the ex- 
 citing and more interesting advance. It seems not so tempting to actually 
 make history by the writing as to metaphorically make it by the concep- 
 tion or experiment. 
 
 We now come to the material side of the subject. 
 
 In the early days, the same hands which mined the iron ore and operated 
 the bellows, also forged the sword and plowshare and touched the goods 
 which were the equivalent in exchange. The records of the development 
 through which the distribution of the steps of such processes has gone is 
 what we call the history of man. It is not always easy to recognize the 
 extent to which this development is progressing in our own time. Sta- 
 tistics ought to show us, but these often fail to impress us. It may be 
 that if used to a limited extent to armor an argument, a few data will be 
 of interest in connection with industrial research. 
 
 The known chemical compounds of the earth are myriads. The still un- 
 known, but knowable, are certainly many myriads more, but any consid- 
 eration of either great mass is too huge a task. We may, however, con- 
 sider for a moment a part of the alphabet from which that language is 
 made. We will consider research as applied to the metallic elements alone. 
 
 There are about 75 elements. About two-thirds are metals. Of these, 
 only a very few can be said to have been the subject of much industrial 
 research. It is impossible to accurately measure the extent to which an 
 element has been studied with a view to its possible use by the race, but 
 we have no difficulty in recognizing that iron and copper have been much 
 
 20 
 
GENERA!,, PHYSICAL AND INORGANIC. 76 
 
 studied, while calcium and silicon have not. In these illustrations we have 
 not selected rare elements. The calcium and silicon, which have been least 
 used by man thus far, are more common than copper or iron. A natural 
 explanation of the lack of development of such elements is a lack of need, 
 but this is possibly incorrect. Copper, iron, etc. , were certainly first obtained 
 by accident as distinct from design. The uses to which they could be put 
 were later developed by trial. The finding of some uses established the 
 further supply, which insured the subsequent discovery of new uses. This 
 mirrors the history now being made by new elements such as silicon. 
 Only in the past year the commercial production of this element has been 
 begun, and about 500 tons were sold for a deoxidizer in steel-making. 
 Thus a substance absolutely out of reach of almost every chemist a few 
 years ago, can now be obtained as cheaply as zinc. 
 
 Similarly, future needs, which only calcium, for example, can meet, 
 are certain to be developed. More calcium will then be made. The cost 
 of production will be reduced and the field of its usefulness will again 
 and ever afterward continue to broaden. Never in the history of the 
 world has the rate of iron production been so great as at present (nearly 
 two million tons a month by the U. S. Steel Company alone). Copper is 
 being mined more rapidly than ever before. We have ourselves seen the 
 industrial birth and growth of a new metal which points to the great 
 possibilities in case of the other unused elements. I refer to aluminium. 
 Only two to three tons were made as late as 1884 while furnaces now 
 exist which are capable of yielding three to four times this quantity every 
 hour of the day and night. Its present uses could only have been, and 
 were, very imperfectly predicted, before actual industrial research made 
 tentative use of it. So it must be with other elements. One is not too 
 bold who assumes that all the elements which are found in abundance 
 will be industrially utilized when they have been economically isolated 
 and thoroughly investigated. 
 
 I am considering the metallic elements only in order to point out in a 
 concrete manner the need of high-quality research, physical, chemical, 
 electrical, etc., in the simplest field. Evidently this field, among com- 
 pounds of the elements, is again bounded only by the infinite. I am im- 
 pressed with the idea that the commonest elements in nature have not 
 been studied with anything like the care which has been given to those for 
 which the demands are already developed. 
 
 In our age, a single investigator will probably not isolate, in large 
 quantities, the metal tellurium, for example, and also put it to use to 
 fill one of his individual needs, as did the warrior who first fashioned an 
 iron blade or axe. The men who develop the myriad uses to which the 
 common element titanium will be put, will have to rely upon the previous 
 work of many investigators. It is in this respect that the conditions are 
 continually changing, and always in one direction. I call it the direction of 
 specific complexity. Our wants are very complex. We are learning to 
 demand very specific properties. It is this fact which makes necessary 
 the research work of the specialist, the specific or narrow investigation 
 of the pure scientist, the pioneer work of the trail-blazer, the crude and 
 hurried trials by the inventor, the long and exacting developments of 
 the practical application in the factory, etc. Demands for new materials 
 do not really precede the discovery of the product, any more than the 
 
 21 
 
77 ORGANIZATION OF INDUSTRIAL RESEARCH. 
 
 demand for high-speed tool steel preceded the discovery of the prop- 
 erties of the chrome-tungsten-iron alloys. With the material dis- 
 covered, its properties known, the world apparently could then hardly 
 get along without it. This means that necessity is not the mother of 
 invention. Knowledge and experiment are its parents. It sometimes 
 happens that a successful search is made for unknown material to fill 
 well recognized and predetermined requirements. It more often happens 
 that the acquirement of knowledge of the previously unknown properties 
 of a material suggests its trial for some new use. These facts strongly 
 indicate the value of knowledge of properties of materials and indicate 
 a way for research. 
 
 Among the recently developed uses for modern metals which were 
 certainly not surmised until the metal itself had been made easily available, 
 are the use of aluminium and silicon as deoxidizers in steel-making, where 
 all the silicon and a large part of the aluminium are now used. This 
 discovery of utility by experiment, rather than the discovery of material 
 by force of necessity, is again illustrated by the metals titanium and vana- 
 dium. The former is used in arc lamps because it was found, by experi- 
 ment, to give a good light. (Your Worcester streets are lighted by it.) The 
 latter has been surprisingly useful in steel-making, where a fraction of 
 i per cent, has been found to impart additional strength to the steel. 
 In this way, about a thousand tons of vanadium are now used annually 
 in America. 
 
 When the first step is taken from the study of the supply, production 
 and utilities of our metallic elements, the next step is apparently along 
 the lines of alloys and we readily see how quickly the field widens. The 
 recent great advances in scientific foundation for much study are to be 
 attributed to the physical chemists, to such men as Tamman and his 
 school. In their work we begin to see the magnitude of the alloy field. 
 There are probably over a thousand pairs of metals whose properties as 
 alloys are still absolutely unstudied, and for alloys of three or more metals 
 the number is legion. 
 
 It seems as though our advance could be quickened by a greater in- 
 timacy with the newly cheapened elements. When sodium, chlorine, 
 bromine, silicon, magnesium, chromium, cobalt, manganese, tungsten, etc., 
 etc., are many times as available or cheap as they were only ten years 
 ago, it is probable that the possible uses are not up-to-date. 
 
 The field of material research really divides into two parts: the search 
 for more economical production and the search for wider application. These 
 two go hand in hand. If the one advances, the other is led along. In 
 this way, in our laboratory, the knowledge of such elements as carbon, 
 as in its forms of graphite in lamp filaments, in motor brushes, in electrodes, 
 etc., has been widely and continually advanced. The result is not 
 a conclusion that we know all about carbon, but rather that it still pre- 
 sents a wonderful field for useful research. 
 
 From the materials worked upon, to the tools is a step. Our experience 
 here is concrete and clear, and we want to record our impressions. Good 
 tools, new tools, rare tools, are most valuable. No good tool lives long 
 for a single use alone. Many times we have questioned the advisability 
 of installing some new apparatus a vacuum furnace, a pair of metal rolls, 
 some special galvanometer, some microscope, an hydraulic press, a power 
 
 22 
 
ORGANIC AND BIOLOGIC AL,. 78 
 
 hammer, a steam digester, etc., etc. Never, after it became a part of the 
 equipment, has it seemed possible to proceed without it. In the single 
 case of the electric vacuum furnace, for example, our laboratory has made 
 almost continual use of from three to eight for the past five years. The 
 laboratory, piped several years ago with high vacuum and with electro- 
 lytic hydrogen, besides steam, air, water and gas, will probably never 
 operate without them. 
 
 Similarly, this applies to a library. In general, the most useful and 
 fertile of our investigators use the library the most. This is as it should 
 be. The recorded research work in a library of a few thousand volumes 
 frequently represents the work of millions of work-hours, and there is 
 little excuse for not availing oneself of the published experience of others. 
 A library containing ten of the leading research journals of the world 
 may be said to have in each volume about 100,000 available brain-power- 
 hours. So a library corresponds to a charged storage battery of great 
 capacity. 
 
 RESEARCH LABORATORY. GENERAL ELECTRIC Co., 
 
 SCHBNBCTADY, N. Y. 
 
 THE ACIDS OF THE PHENYLPROPIOLIC SERIES AND THEIR 
 CONDENSATION TO NAPHTHALENE DERIVATIVES. 1 
 
 BY JOHN E. BUCHER. 
 Received December 9, 1909. 
 
 In an investigation of the action of acetic anhydride on acids of the 
 acetylene series in 1895, Michael and Bucher 2 obtained the anhydride 
 of a new acid from phenylpropiolic acid. Three years later, 3 after a 
 thorough study of the compound, they proved it to be the anhydride of 
 i-phenyl-2,3-naphthalenedicarboxylic acid. It was found to have the 
 composition corresponding to the formula C^H^Og and a molecular 
 weight of 274. 
 
 This corresponds to the composition of a phenylpropiolic anhydride 
 (C 8 H 5 .C H= C.CO) 2 O, but the acid obtained from it was found to be sat- 
 urated and entirely different from phenylpropiolic acid. This structural 
 formula evidently does not represent its constitution. 
 
 It seemed probable that three molecules of the acid might have 
 polymerized to triphenyltrimesic acid in a manner analogous to the for- 
 
 C.CO 2 H 
 
 C 6 H 5 . 
 H0 3 C.cl Jc.C0 2 H 
 
 C.C 8 H 8 
 
 1 Presented at the Second Decennial Celebration of Clark University, Worcester, 
 Mass., September 14, 1909. 
 7 Ber., 28, 2511 (1895). 
 1 Am. Chem. ] ., 20, 89 (1898). 
 
 23 
 
213 
 
 ACIDS OF THE PHENYLPROPIOLIC SERIES. 
 
 mation of benzene from acetylene. The resulting acid was found to be 
 dibasic and to have only two-thirds of the required molecular weight. 
 These facts showed conclusively that the compound is not the anhydride 
 of triphenyltrimesic acid. 
 
 It was then thought possible that the compound might be the anhy- 
 dride of diphenyltetrenedicarboxylic acid. 
 
 C 8 H 6 .C r -i C.C0 2 H 
 
 C,H 8 .C 
 
 C.CO 3 H 
 
 This acid would contain two carboxyl groups in the ortho position and 
 it would be dibasic. One might expect benzil among the oxidation 
 products of such an acid but many experiments failed to show the slightest 
 trace of this substance. It was not possible to find any evidence in 
 favor of the tetrene formula. 
 
 As none of these three formulas corresponded to the compound, it 
 was evident that the polymerization of the phenylpropiolic acid must 
 have proceeded in a very unusual manner. 
 
 H0 2 C. 
 H0 2 C. 
 
 ,C.CO 2 H 
 .CO,H 
 
 CH 
 
 24 
 
ORGANIC AND BIOLOGICAL. 214 
 
 They finally succeeded in isolating diphenyltetracarboxylic- and ortho- 
 benzoylbenzoic acids from its oxidation products and in preparing its 
 hydrocarbon. The hydrocarbon was also oxidized to orthobenzoyl- 
 benzoic acid. The preceding formulas show these transformations. 
 
 These facts can only be explained by the above constitutional formula 
 and the compound is therefore the anhydride of i-phenyl-2,3-naph- 
 thalenedicarboxylic acid. 
 
 Later, several investigators who evidently had overlooked the above work 
 obtained this compound. Basing their reasoning on insufficient experi- 
 mental evidence, they described the substance first as the anhydride of 
 triphenyltrimesic acid and afterwards as that of diphenyltetrenedicar- 
 boxylic acid, representing structural formulas which had already been 
 shown to be untenable by Michael and Bucher. For example, Lanser 1 
 obtained the compound by heating phenylpropiolic acid with phosphorus 
 oxychloride, and assigned the formula C^HgoOg for triphenyltrimesic 
 anhydride without making molecular weight determinations. 
 
 A little later Manthey 2 determined the molecular weight thus showing 
 the formula to be C 18 H 10 O S and that the constitution must be different 
 from that assigned by Lanser. This evidence together with the fact 
 that the acid contains the two carboxyl groups in the ortho-position, 
 led him to assign the tetrene formula. 
 
 In a later paper, Lanser and Halvorsen 8 acknowledge the correctness 
 of Manthey 's experimental work and they also accept the tetrene formula. 
 The reactions which they study would, however, apply equally well to 
 other ortho-dibasic acids. 
 
 Ruhemann and Meriman 4 also obtained the anhydride in studying the 
 action of phenylpropiolyl chloride on acetone in pyridine solution. 
 They proved the identity of their compound with that of Lanser and 
 regarded it as a terene compound as they did not investigate its con- 
 stitution. 
 
 Michael 5 next showed that the compound described by these investi- 
 gators is i-phenyl-2,3-naphthalenedicarboxylic anhydride. He proved 
 this by preparing a specimen by Lanser's method and finding it identical 
 in every respect with a specimen prepared by the method of Michael 
 and Bucher. 
 
 Recently, Stobbe* obtained this anhydride by the action of light on 
 dibenzalsuccinic anhydride. Failing to get diphenyltetracarboxylic 
 acid by direct oxidation but obtaining ortho-benzoylbenzoic acid, he 
 claimed to have shown the truth of the naphthalene formula of Michael 
 and Bucher for the first time. 
 
 These investigators 7 showed that his failure to get the diphenyltetra- 
 carboxylic acid was due to incomplete oxidation 8 and that they had 
 
 1 Ber., 32, 2478 (1899). 
 
 2 Ibid., 33, 3083 (1900). 
 1 Ibid., 35, 1407 (1902). 
 
 4 J. Ckem. Soc., 87, 1389 (1905). 
 
 8 Ber., 39, 1908 (1906). 
 
 Ibid., 40, 3372 (1907). 
 
 7 Ibid., 41, 70 (1908). 
 
 1 Tins JOURNAL, 30, 1246 (1908). 
 
 25 
 
215 
 
 ACIDS OF THE PHENYIvPROPIOLIC SERIES. 
 
 noticed the formation of ortho-benzoylbenzoic acid by the direct oxida- 
 tion 1 of the anhydride as well as from the hydrocarbon. 
 
 Pfeiffer and Moller 2 have polymerized phenylpropiolic ester to the 
 ester of i-phenyl-2,3-naphthalenedicarboxylic acid by simply heating 
 to 200. They point out that aromatic acetylene derivatives may thus 
 be polymerized to naphthalene derivatives without the use of condensing 
 agents. The earlier work of Lanser also shows this since Michael has 
 shown that the so-called triphenyltrimesic acid is really a naphthalene 
 derivative. Lanser obtained the anhydride of this acid by heating 
 phenylpropiolic acid to a temperature above 200. Pfeiffer and Holler's 
 work, however, illustrates the additional fact that anhydride formation is 
 not essential for this naphthalene condensation. 
 
 I have confirmed Lanser's experiment and have been able to get a 
 much better yield of the ester of the naphthalene acid than Pfeiffer and 
 Moller got. In my experiment, however, the phenylpropiolic ester was 
 polymerized by heating it with acetic anhydride instead of heating it 
 alone. 
 
 These investigations show that phenyl propiolic acid and its ester or 
 chloride can be polymerized in a number of different ways to naphthalene 
 derivatives but that the original method of Michael and Bucher which 
 gives a quantitative yield is still the best. The following formulas in- 
 dicate how this change takes place : 
 
 C.COjH 
 
 CH 
 
 This work has been continued in this laboratory for a number of years 
 in order to determine whether this transformation is general or not. 
 Besides phenylpropiolic acid, eleven of its substitution products 
 have been examined thus far and in every case they polymerized, on 
 heating with acetic anhydride, to derivatives of i-phenyl-2,3-naph- 
 thalenedicarboxylic anhydride. The facts thus far obtained justify the 
 statement 3 that phenylpropiolic acid and its substitution products show a 
 strong tendency to polymerize, with the wandering of an ortho hydrogen atom, 
 to phenylnaphthalene derivatives. 
 
 1 Am. Chem. J., 20, 112 (1898). 
 
 Bar., 40, 3839 (1907). 
 
 THIS JOURNAL, 30, 1262 (1908). 
 
 26 
 
ORGANIC AND BIOLOGICAL. 2l6 
 
 In fact, this kind of polymerization is the only form which has been 
 thus far obtained from aromatic propiolic acids. 
 
 In this work much time was spent in preparing the aromatic propiolic 
 acids as it was usually necessary to either prepare new compounds or 
 else to improve the methods of preparation of acids which were already 
 known. In most cases methods were found by which these interesting 
 acids could be prepared readily from comparatively inexpensive materials 
 providing that suitable precautions were observed. 
 
 Phenylpropiolic acid was prepared in the usual way from cinnamic 
 acid by making cinnamic ester dibromide. It is well known that alco- 
 holic potash converts this into a mixture of the salts of allo-bromocinnamic 
 acid and bromocinnamic acid and that the latter is easily converted into 
 phenylpropiolic acid by the loss of hydrobromic acid. The former acid 
 is so stable, however, that it is not practicable to convert it into phenyl- 
 propiolic acid directly by further heating with alcoholic potash. It can, 
 however, be converted into the isomeric acid by simply heating it. This 
 acid can then be converted, in turn, into phenylpropiolic acid. This 
 change of the labile bromo acids into the corresponding isomeric acids 
 was found to be quantitative in several cases. In the case of the allo- 
 bromocinnamic acid it was noticed that when it was heated with acetic 
 anhydride to 100 its own anhydride was produced but at a higher tem- 
 perature this was transformed into the bromocinnamic anhydride. The 
 latter could then be transformed into phenylpropiolic acid. From this, 
 it is evident that it is not necessary to use pure phenylpropiolic acid 
 in this work. It generally seemed desirable, however, to separate the 
 acids first. A very good way of doing this is to crystallize them from 
 carbon disulphide or from carbon tetrachloride. In this way it is possible 
 to separate much of the phenylpropiolic acid from the more soluble allo- 
 bromocinnamic acid. 
 
 In some other cases, the potassium salts of the propiolic acids were 
 found to be very sparingly soluble in the alcoholic potash, thus yielding 
 the pure acids at once. In all cases the potassium salts of the labile 
 bromocinnamic acids were found quite soluble while the ammonium salts 
 of the isomeric acids were very sparingly soluble. These properties were 
 found very useful in separating the resulting phenylpropiolic acids from 
 these labile substituted bromocinnamic acids which were formed. 
 
 The meta- and para-nitrophenylpropiolic acids can be prepared from 
 the corresponding nitrobenzoic aldehydes by Perkin's synthesis. In 
 some other cases Claissen's synthesis was found preferable to that of Per- 
 kin. 
 
 It was also found that the ortho- and para-nitrophenylpropiolic acids 
 could be converted into the corresponding halogen acids by means of the 
 diazo reaction. 
 
 Besides phenylpropiolic acid, the following substitution products were 
 prepared : Piperonylpropiolic acid, o-chloro-, o-bromo-, w-nitro-, m-chloro-, 
 p-nitro-, p-chloro-, p-bromo-, p-iodo-, />-methoxy-, and ^-methylphenyl- 
 propiolic acids. These all polymerize readily to derivatives of i-phenyl-2,3- 
 naphthalenedicarboxylic anhydride when they are heated with acetic 
 anhydride. In the earlier work it was found very difficult to prove this 
 constitution for these products. The method used in case of the first 
 compound has already been described. The meta- and para-nitro 
 compounds were oxidized and then converted into diphenyltetracar- 
 
 27 
 
217 
 
 ACIDS OF THE PHENYLPROPIOLIC SERIES. 
 
 boxylic acid thus showing them to be naphthalene derivatives. By 
 means of the diazo reaction, they were then converted into the halogen 
 derivatives identical with those obtained by direct polymerization. This 
 showed the latter to have the same constitution. The constitution of 
 the product from the para-methylphenylpropiolic acid was established 
 by oxidizing it to a diphenylpentacarboxylic acid. In more recent 
 work the very efficient method of oxidizing to benzenepentacarboxylic 
 acid described below was used. By means of this method, which depends 
 on the catalytic action of manganese nitrate in fuming nitric acid, eleven 
 of these acids were oxidized to benzenepentacarboxylic acids, thus con- 
 firming the naphthalene constitution which had previously been assigned 
 for some of the substances. 
 
 The following description gives an idea of some of the transformations 
 which these substances undergo: They are all ortho-dibasic acids from 
 which water splits out easily on heating. In fact, the first acid obtained 
 is partially converted into its anhydride even on crystallizing it from only 
 moderately heated glacial acetic acid. In this way, I obtained eight 
 grams of the anhydride from twenty grams of the acid. This loss of 
 water in crystallizing the acid from hot solvents led to the statement, 
 made in the first description, that the acid passed into the anhydride 
 spontaneously. This statement was corrected in a later paper by Michael. 
 All of these acids have this general property and some of them, as well as 
 their oxidation products, may show properties similar to those noticed 
 by Orndorff in the case of tetrachlorophthalic acid. 
 
 The acids all necessarily contain a carboxyl group with both ortho 
 positions substituted. According to V. Meyer's observations one might 
 expect difficulty in esterifying these acids. This was found to be the 
 case, little or no neutral ester being found, on heating the substances with 
 alcohol and sulphuric acid under the usual conditions. If more sulphuric 
 acid is used and the heating continued for a longer time from 40 to 60 
 per cent, of neutral ester may be obtained. 
 
 Sulphuric acid converts the i-phenyl-2,3-naphthalenedicarboxylic 
 acid into red allo-chrysoketonecarboxylic acid. 
 
 H 
 
 CH 
 
 .COjH 
 .CO.H 
 
 .00,11 
 
 H 
 
 JCH 
 
 CH CH 
 
 I. II. 
 
 When this red acid is heated to 218 with potassium hydroxide, it is 
 
 28 
 
ORGANIC AND BIOLOGICAL. 
 
 218 
 
 changed practically quantitatively into a new i-phenylnaphthalenedi- 
 carboxylic acid. 
 
 CH CH 
 C 
 
 Formulas I, II and III show a method of transferring a carboxyl 
 group from the ortho position on one ring to the corresponding position 
 on the other ring. When the new acid (III) is heated with sulphuric acid, 
 a new red acid different from the allochrysoketonecarboxylic acid (II) is 
 obtained. 
 
 The oxidation of these naphthalene acids in alkaline potassium per- 
 manganate solution has already been described. The yield of diphenyl- 
 tetracarboxylic acid is usually small, since the intermediate ketonic acids 
 are very stable towards alkaline potassium permanganate. 
 
 HO,C.O~ 
 / \ 
 HOC 
 
 H0 2 C.C 
 
 These ketonic acids are very easily oxidized to diphenyltetracarboxylic 
 acids when the solution is acidified. Formulae I, IV, V and VIII 
 indicate these reactions. These acids are obtained in the form of sirup- 
 like solutions and they resemble phthalonic acid closely. Heated with 
 caustic alkalies, they yield diphenyltricarboxylic acids and oxalic acid. 
 
 29 
 
219 
 
 ACIDS OF THE PHENYLPROPIOUC SERIES. 
 
 On reduction with hydriodic acid, the weto-glyoxylic acid (V) first yields 
 methyldiphenyltricarboxylic acid (VI) which then reduces at a higher 
 temperature to a methylfluorenecarboxylic acid. The isomeric ortho- 
 glyoxylic acid (IV), aven at the boiling point of hydriodic acid, reduces 
 to a fluorenetricarboxylic acid (VII). 
 
 CH CH 
 
 H 8 C. 
 
 HO 2 C. 
 
 HO 2 C. 
 
 C.CO 2 H 
 
 C.CO,H 
 
 VII. 
 
 This shows the ease with which diphenylcarboxylic acids close the ring 
 to form fluorene derivatives. The same tendency is shown by the action 
 of sulphuric acid on diphenyltetracarboxylic acid (VIII) in forming the 
 yellow diphenyleneketonetricarboxylic acid (IX), which can be reduced 
 to the acid represented by formula VII. I have found this closing of the 
 ring on heating to 100 with sulphuric acid, to take place when all the 
 carboxyl groups were on the same ring but generally not when the car- 
 boxyl groups were on different rings. In diphenyleneketonecarboxylic 
 acids of the general form IX, the ring is broken in such a way, on heating 
 with potassium hydroxide, that the carboxyl group is transferred from 
 the ortho position on one ring to the corresponding ortho position on the 
 other. 1 In this case, about 299 parts out of 300 are changed in this way 
 making the process practically quantitative. The following formulas 
 show these changes. 
 
 The very sharp breaking of the ring at a in formula IX and in the 
 similar case of the red acid (II) indicates a tendency to remove the 
 carboxyl groups as far as possible from each other and suggests the pos- 
 sibility of its giving a means of testing the constitution of the resulting 
 acid. For example Bamberger and Hooker, 3 after heating a yellow 
 diphenyleneketonedicarboxylic acid from retene with caustic alkali, 
 represent the resulting white diphenylenetricarboxylic acid as having 
 the three carboxyl groups on the same ring. This seemed scarcely pos- 
 sible in view of the above facts and an examination showed the acid to 
 have a different structure. 
 
 The yellow diphenyleneketonetricarboxylic acid (IX) also furnishes 
 a means of oxidizing these i-phenyl-2,3-naphthalenedicarboxylic acids 
 or diphenylpolycarboxylic acids (like I and VIII) to benzenepentacar- 
 
 1 THIS JOURNAL, 30, 1261 (1908). 
 1 Ann., 229, 159 (1885). 
 
ORGANIC AND BIOLOGICAL. 
 
 22O 
 
 CH 
 
 ,C.CO 2 H 
 
 ic.co 2 H 
 
 C.CO 3 H 
 XI. 
 
 boxylic acids. The latter acid (VIII) is very stable towards alkaline potas- 
 sium permanganate as on heating for six weeks I recovered 28 per cent, 
 of unchanged acid and could not isolate any benzenepentacarboxylic acid. 
 The yellow acid (IX), however, decolorized the theoretical quantity of 
 permanganate in less than two hours. The very soluble acid product 
 was not completely oxidized but it yielded benzene for the hydrocarbon. 
 Many experiments were made in attempting to complete the reaction 
 but without success. Even heating on the water bath with fuming nitric 
 acid did not aid very much. A small quantity of manganese nitrate 
 was then added to the hot nitric acid. Brisk effervescence began at once 
 and in a few moments pure benzenepentacarboxylic acid separated front 
 the liquid. The yield in this experiment was about 90 per cent, of the 
 theory. The manganese nitrate is evidently a very efficient catalytic 
 agent in this case. This method was also applied to the acids without 
 first converting them into ketone derivatives, and, in eleven cases out of 
 the twelve tested, benzenepentacarboxylic acid was found. Not only 
 does this give a very powerful method for determining constitution but 
 
221 CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 
 
 it gives a very easy method of preparing the hitherto almost inaccessible 
 benzenepentacarboxylic acid. It also serves for the preparation of 
 other benzene polycarboxylic acids. Bamberger and Hooker's diphenyl- 
 eneketonedicarboxylic acid from retene can be oxidized in a few hours 
 to two isomeric benzenetricarboxylic acids, thus showing that the constitu- 
 tion given for retene and all its derivatives is incorrect. 
 
 The above work dealing with the action of acetic anhydride led to the 
 supposition that anhydrides 1 might be prepared from meta- and para- 
 phthalic acids and their substitution products. On trying the experi- 
 ment it was found that such anhydrides could be obtained quantitatively 
 by heating a solution of the acid in acetic anhydride to 200 until the 
 excess of reagent was distilled off. These products apparently have a 
 very high molecular weight. A preliminary determination, in nitro- 
 benzene by the boiling point method, for the anhydride from chlorotere- 
 phthalic acid, [C 6 H B Cl(CO) 2 O]x, indicates that it may be as high as 1500 
 or 2000. 
 
 A part of this work has been carried on with the aid of my students 
 and I wish especially to acknowledge the valuable assistance of G. F. 
 Parmenter, N. A. Dubois, V. S. Babasinian, M. L. Dolt, W. C. Slade 
 and F. Keyes. 
 
 The more important results of this work thus far are as follows : 
 
 1. Satisfactory methods for the preparation of a number of aromatic 
 propiolic acids. 
 
 2. The polymerization of these acids to derivatives of i-phenyl-2,3- 
 naphthalenedicarboxylic acids giving a quantitative method of syn- 
 thesis. 
 
 3. Syntheses of acids of the diphenyl, fluorene and diphenyleneketone 
 series and a study of their characteristic reactions. 
 
 4. Syntheses of benzenepentacarboxylic acid and other benzene- 
 polycarboxylic acids. 
 
 5. The determination of the constitution of retene and its derivatives. 
 
 6. The preparation of anhydrides from meta- and para-phthalic acids 
 and their substitution products. 
 
 BROWN UNIVERSITY, PROVIDENCE, R. I. 
 
 CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 2 
 
 BY JULIUS STIEGLITZ. 
 Received December 2, 1909. 
 
 I shall not attempt to discuss to-day the general subject of catalysis 
 but shall use the short time rather to present briefly some results 3 in 
 certain lines of our work which seem to shed some light on three funda- 
 mental points of interest in catalysis, namely, on the questions how in 
 
 1 THIS JOURNAL, 30, 1263 (1908) and 31, 1319 (1909). 
 
 1 Presented at the Second Decennial Celebration of Clark University, Worcester, 
 Mass., September 15, 1909. 
 
 ' Certain parts of the work are still being carried out as indicated below and 
 for such parts this report is preliminary to a final one. Complete discussion of the 
 several parts lay outside the limits of this paper and will be brought in in later special 
 reports. 
 
 32 
 
ORGANIC AND BIOLOGICAL. 222 
 
 certain cases a catalytic agent does its work, why it does it, and what 
 limitations there are to its action. 
 
 It may be recalled that an imido ester, such as methyl imido benzoate, 
 is very slowly decomposed by pure water. One of the decompositions 
 it undergoes under these conditions is into ammonia and methyl benzoate 1 
 as expressed in the equation 
 
 C 6 H 5 C( : NH)OCH 3 + H 2 O > C 6 H 6 CO 2 CH 3 + NH 3 . (i) 
 The addition of an acid, say hydrochloric acid, enormously accelerates 
 this otherwise extremely slow action and we were able to show that the 
 acceleration is due to the fact that the reacting component in this decom- 
 position is the positive ion of the ester, 2 as expressed in the equation. 
 
 C fl H 5 ( : NH 2 +)OCH 3 + H 2 O ^ C 6 H 5 CO 2 CH 3 + NH 4 +. (2) 
 In arriving at this conclusion, account had to be taken of the so-called 
 "salt-effect" or "salt-acceleration" produced by the presence of elec- 
 trolytes, entirely analogous to the "salt-effect" in other decompositions 
 in which water is a reacting component, as in the catalysis of esters by 
 acids. This salt-effect being allowed for, the velocity of decomposition 
 of an imido ester by water in the presence of acids is given in the equation 3 
 
 dxfdi = K v(ion} X C^ M/ . * X [C H X C OH }. (3) 
 
 I have not time more than to mention the fact that it was shown that 
 the same fundamental equation may be applied to the saponification of 
 ordinary esters under the influence of acids, the main difference being 
 that for such exceedingly weak oxonium bases as esters are the con- 
 centration of the positive ester ion is practically proportional to the 
 concentrations of the ester and the hydrogen ion present at any moment, 
 so that we may transform (3) into 4 
 
 dx/dt = K V X C ester XC H X [C H X C OH ] (4) 
 
 which is also the equation based on experience. 
 
 The work on which the above conclusions were based was carried 
 out wholly with the hydrochlorides of the imido esters. More recently 
 we have also carried out measurements with the hydrobromides and 
 nitrates, and begun work also with sulphates; if the positive ion is the 
 reacting component, then, determining rigorously the degree of ionization 
 and making rigorous allowance for the salt-effect, we should find that the 
 velocity constant for the decomposition of the positive ion in the chloride 
 solution should also satisfy the observed rates of decomposition of these 
 other salts. For the rigorous treatment, the "salt-effect" produced by 
 the chlorides, bromides, nitrates, etc., has to be determined experimen- 
 tally and this has been carried out 5 with the chlorides and bromides, 6 
 mixtures with varying amounts of the potassium and sodium salts being 
 examined, the degrees of ionization of each salt in the mixture being 
 1 Stieglitz, Report International Congress of Arts and Science, St. Louis, 4, 276 
 (1904), and Am. Chem. J., 39, 29 (1908). 
 
 * Stieglitz with Derby, McCracken, Schlesinger, Am. Chem. J., 39, 29, 166, 402, 
 437, 586, 719. 
 
 3 Cp os . est. ion 1S a function of x. 
 
 * Cgster is a function of x. 
 
 ' W. W. Hickman, Dissertation, 1909. 
 
 ' Mr. Weatherby is completing the work begun by Mr. Hickman on the nitrates 
 and sulphates. 
 
 33 
 
223 CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 
 
 determined with the aid of the principle of isohydric solutions, which 
 was proved to apply to such mixtures. 1 The salt-effect is, except for 
 minute quantities of salt, proportional to its concentration or rather, 
 more probably, only to the concentration of the ionized part of the salt.. 
 The salt-effect is an acceleration and if we call K V (i on ) the velocity of 
 decomposition of the imido ester ion in the absence of any salt at all, 
 this velocity will be increased proportionally to some specific acceleration 
 factor A, and to the concentration ma of the ionized part of A salt. So we 
 have 
 
 K ,(M)ob,. = K ,<io)o (1 +Ama). (5) 
 
 Kv(ion)obs. is the constant calculated according to equation (3) from 
 the observations without any allowance for a salt-effect. 
 
 Kv(ion)o, the velocity constant when the salt effect is eliminated, is easily 
 found by extrapolation from the observations when imido ester salts 
 are present without added salts, A from the results obtained when salts 
 have been added. We arrived thus empirically at the rather unexpected 
 result that the accelerating factor A is approximately the same for 
 sodium, potassium and lithium chlorides and for the bromides as well 
 as for the chlorides, viz., about 185 per cent, per gram molecule of fully 
 ionized salt. Table I illustrates this fact for potassium chloride and 
 potassium bromide. K v is the velocity coefficient calculated without 
 regard to the degree of ionization of the imido ester salt, a is the degree 
 of ionization of the salt calculated with the aid of the principle of iso- 
 hydric solutions. In the columns headed "found" are given the values 
 obtained for K v \ a by experiment; in the columns headed "calculated" 
 are the values obtained according to equation (5), in which the velocity 
 coefficient K v (i on ) in the absence of any salts at all is taken as 164 and the 
 salt acceleration factor A is taken as 185 per cent, for both series. 
 
 TABUJ I. 1 
 
 KCl. KBr. 
 
 43430 K-oja. 43430/S^/a. 
 
 K Hal. 
 
 m. Found. Calculated. Found. Calculated, 
 
 o 176 176 176 177 
 
 O.I 191 190 191 190 
 
 0.2 213 214 209 215 
 
 0.25 227 226 230 227 
 
 0.333 247 245 (268) 247 
 
 I wish to emphasize this result because the work of others, notably of 
 Arrhenius and Euler, with cane-sugar and esters, shows varying specific 
 accelerating factors for these salts. I believe our work has the advantage 
 of our knowing from conductivity measurements the degrees of ioniza- 
 tion of the imido ester salts as well as of the added electrolyte so that 
 there seems to be no unknown factor left in our estimations. But we are 
 simply presenting these results for the time being as an empirical contri- 
 bution to the whole question of catalysis and we do not consider the 
 very complex question of "salt catalysis" as at all settled. 3 
 
 . * Edith E. Barnard, Dissertation, 1907. 
 3 Taken from W. W. Hickman's dissertation. 
 
 3 Work on "salt catalysis" is being continued by L. S. Weatherby, preliminary 
 results by Mr. Hickman on the effect of sulphates indicated an abnormally high effect. 
 
 34 
 
ORGANIC AND BIOLOGICAL. 224 
 
 With the aid of the determination of the salt factor for chlorides and 
 bromides we have been able to show that the positive ester ion shows 
 indeed the same rate of decomposition irrespective of its origin from either 
 of these salts and very probably also for the nitrate 1 (see the values for 
 K v i a for the three salts in equi-molar concentrations as given in Table II). 
 This is exactly what our theory would require, namely, that the simple 
 reason why the addition of an acid accelerates this decomposition is that 
 it forms a salt whose positive ion is the reacting component and that the 
 concentration of the ion is enormously increased when the catalyzing 
 acid is added to the free ester, which is a very weak and therefore little 
 ionized base. . 
 
 TABLE II.* ETHYL IMIDO BENZOATE. 
 
 Hydrochloride. Hydrobromide. Nitrate. 
 
 ^. 0.8 K v .* JftjT * Kv* Kfa. o. K v * Kvla. 
 
 0.05 77.8 136 175 75-9 133 i?6 75-1 133 177 
 
 o.i 71.8 132 185 69.4 128 184 68.3 127 186 
 
 0.2 64.5 121 188 61.7 119 193 60.4 118 195 
 
 0-33 57-7 "4 198 54-7 108 198 52.7 107 201 
 
 It was suggested by Arrhenius and emphasized by Euler that the 
 
 salt acceleration is probably largely due to the increased ionization of 
 
 water in the presence of electrolytes, but quantitative evidence in support 
 
 of such a conclusion has not been brought, as far as I am aware. In view 
 
 of the increase observed by Arrhenius arid others 5 in the strength of other 
 
 acids in the presence of added foreign salts, e. g., of acetic, formic and 
 
 carbonic acids in the presence of sodium chloride, it seems a sufficiently 
 
 rational assumption that water should show a similar increased ionization. 6 
 
 The imido esters, enabling us to measure the actual concentration of the 
 
 reacting imido ester ion, gave us an opportunity to bring experimental 
 
 evidence strongly supporting this view. From equation (3) it is obvious 
 
 that if the salt acceleration is due to the increased ionization of water, 
 
 viz., an increase in the value of the third factor, (C H X COM) then, Cp os . M <. i on 
 
 being known by experiment, the velocity constant K v (io n ) calculated 
 
 -without taking any increased value of [C# X COH] i nto account, should 
 
 increase in the same proportion for all the imido esters for the same 
 
 concentration of added salt ions, irrespective of the fact that, according 
 
 to the ester used, the decomposition may be a comparatively slow or a 
 
 very fast one. We have found this to be true 7 all the esters used show 
 
 the same acceleration per gram molecule ionized salt i. e., close to 
 
 185 per cent, per gram molecule ionized potassium chloride, etc. 8 
 
 Having found that the reacting component in these and a number 
 of other actions under the influence of acids is the positive ion of a salt 
 formed with the acid, we were naturally most interested in the question 
 
 1 The salt effect for nitrates is now being determined. 
 1 Taken from W. W. Hickman's dissertation. 
 
 3 Taken from Edith E. Barnard's dissertation. 
 
 4 Taken from Schlesinger's results, Loc. cit. 
 
 * E. J. Szyszkowski, Z. physik. Chem., 58, 419. 
 
 See a discussion of the other side of this question by Acree, Am. Chem. J., 41, 474- 
 
 7 Dissertation of Edith E. Barnard and W. W. Hickman. 
 
 8 The investigation of the ionization of water in salt solutions is being continued 
 with other substances and by other methods. 
 
 35 
 
225 CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 
 
 why the ion should be so reactive, why it should be so important a com- 
 ponent. We can hardly consider the decompositions to be purely ionic 
 reactions, 1 comparable with the hydrolysis of salts in aqueous solutions, 
 as was mistakenly assumed, for instance, by Euler and by Kastle. Such 
 assumptions run counter to the law of mass action applied rigorously in 
 the analysis of the conditions. 1 The law is, however, in agreement with 
 the assumption 2 based on experience gained in organic chemistry that the 
 following are the stages for the action : 
 
 . 
 
 C,H s Cf +H+ + OH- *-C,H 6 C OIH *-t^H 5 CO,CH, + NH,+ (6) 
 
 \OCH, 
 
 Now, we may well ask why this should be an enormously faster action 
 than the entirely analogous possible action of water on the non-ionized 
 free ester, which, it is clear, could proceed in a very similar series of stages 
 as expressed in the equations : 
 
 C,H 6 C^ +H+ + OH- C,H S C O:H * C,H 6 CO,CH a +NH,,. (6') 
 \OCH. \oj- 
 
 For me, one of the most interesting and important features of our 
 work is found in the unmistakable way in which the fact is brought out 
 more and more clearly that the accelerating or catalytic effect of the 
 acid is most intimately associated with the transformation, in acid solu- 
 tion, of the positive ion of a weaker base into that of a stronger one 
 the results no doubt of the principle of the loss of a maximum amount 
 of free energy. 3 This is shown most strikingly in the following illustra- 
 tion: whereas the above imido esters are very rapidly decomposed by 
 water in the presence of acid, this is not the case for the closely related 
 compounds, the urea ester salts, which, structurally considered, could 
 react quite as easily with water but are as a matter of fact quite stable 
 in acid solution. The transformation 
 
 /NH 2 + 
 NH 2 C< ' +HOH >NH 2 C OH -^ NH 4 ++H 2 NCOOCH 3 (7) 
 
 only takes place to a very slight extent at 100, and at ordinary tempera- 
 tures, where imido ester salts are completely decomposed in one to ten 
 hours, the urea ester salts have not been observed to decompose at all. 4 
 In this case we have the notable fact that such a transformation would 
 involve the change of a salt of a stronger base into that of a much weaker 
 one an ammonium salt and this does not take place. To test the 
 legitimacy of our reasoning we recently examined the behavior of ben- 
 zoyl urea ester salts: the benzoyl urea esters form very much weaker 
 
 1 See a more complete discussion by Stieglitz, Am. Chem. J ., 39, 402. 
 
 2 Stieglitz, Loc. cit. 
 8 Ibid. 
 
 * The degree of stability is being examined quantitatively. 
 
 36 
 
ORGANIC AND BIOLOGICAL. 226 
 
 bases than ammonia and our reasoning would lead us to expect that they, 
 in turn, ought to be decomposed quite as smoothly in acid solution as the 
 imido esters. Such is, in fact, the case; 1 urethanes and ammonium salts 
 readily result according to the equation 
 
 C 6 H 5 CO.NH.Cf + HOH > NH 4 + + C 6 H 5 CONHCOOCH 3 . (8) 
 X OCH, 
 
 We find then that perfect analogy in structure is of far less importance 
 in determining the result of the action of water than a definite physico-chemical 
 relation subject to quantitative measurement. 
 
 This is again brought out beautifully by the behavior of the urea esters 
 towards ammonia. The imido esters give with ammonia amidines and 
 again the action is accelerated by the addition of an acid or an ammonium 
 salt and, as we shall see presently, this is due to the fact that again it is 
 the positive ester ion that reacts with ammonia, an amidine resulting 
 according to the equation 
 
 C 6 H 5 C( : NH 2 +)OCH, + NH, * C a H 6 C( : NH 2 +)NH 2 + HOCH 3 (9). 
 
 Now, urea esters which, as explained above, would not react with water 
 in acid solution because the salt of a stronger base would be converted 
 into the salt of a weaker one if they did react, would give with ammonia 
 guanidines which are still stronger bases than they are themselves. 
 They should, therefore, according to this theory, react with ammonia in 
 the presence of an acid ; as a matter of fact they do, producing guanidines 
 very readily, and we were able to prove again that the velocity of the 
 formation is proportional to the concentration of the positive ester ion; 2 
 in fact, until our theory led us to recognize the importance of having a 
 salt-forming acid present, all our efforts to prepare guanidines from 
 urea esters by using ammonia alone had proved futile; so that this 
 theory seems to agree equally well with the reactions of a given compound 
 which do occur as with those which do not take place. 
 
 We have found too that in series of structurally closely related esters 
 where what might be called the structural and stereochemical resistances 
 to the action are perhaps approximately the same, the transformation 
 of the positive ion of a weaker base in the presence of acids into that of a 
 given stronger base, say into the ammonium ion, proceeds with the greater 
 velocity at a given temperature the weaker the original base is. 3 This brings, 
 as far as I am aware, the first complete experimental proof of a theory 
 which others, notably van't Hoff and Euler suspected to be true, 4 although 
 there appeared so many marked contradictions to the assumption that 
 the theory appeared at best a very uncertain one. For instance, Hemp- 
 tinne 5 and Lowenherz, 6 working on this problem at van't Hoff's sug- 
 gestion, obtained the following results for the saponification of esters by 
 acids : 
 
 1 J. C. Moore's dissertation, 1909. 
 
 1 R. A. Hall's dissertation (1907). 
 
 Cf. Stieglitz, Loc. cit., and McCracken, Loc. cit. 
 
 4 See the discussion by Euler, Z. physik. Chem., 36, 410. 
 
 8 Ibid., 13, 561. 
 
 Ibid., 15, 395. 
 
 37 
 
227 CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 
 
 TABLE III. 1 
 
 Ester. Velocity constant. loniz. const, of the acid. 
 
 HCOOC 2 H 5 O.H 21 X 10- 
 
 CH 3 COOC 7 H 5 0.0057 i. 8X10- 
 
 C1CH 2 COOC 2 H S 0.0033 155 X io- 
 
 C1 2 CHCOOC 2 H 5 0.0053 5ioo X io- 
 
 CH 3 CH 2 COOC 2 H 5 0.0061 i .3 X io~ 
 
 Assuming, as Euler did, that the strongest acids produce the weakest 
 bases in their esters, one might expect the positive ions of the chloroacetic 
 acid esters to be saponified most rapidly to give the positive ion of a 
 given stronger base, the oxonium base of ethyl alcohol. As a matter of fact 
 the velocity constants in the above table do not tell us anything at all 
 as to whether that is so or not and that is why the theory, heretofore, has 
 appeared as an unproved one; obviously it does not follow from the data 
 in Table III, where the weakest bases, dichloroacetic ester and chloroacetic 
 ester, have the smallest, not the largest, velocity constants of decomposi- 
 tion. But the fact that, for instance, the velocity coefficient for the 
 saponification of dichloroacetic ester is even smaller than that for ethyl 
 acetate does not mean anything at all in regard to the real relative rates of 
 transformation of their positive ions: there is a second factor involved, 
 namely, the concentrations of the positive ions of the esters are 
 dependent on the strength of the esters as oxonium bases, as expressed 
 in our fundamental equations for the catalysis of an ester by an acid. 2 
 In our fundamental equation 
 
 dx/dt = K v(ion) X C^ M , ^ X [C H X C OH ] (io) 3 
 
 we may substitute for C^j. est . ion the relation expressed in : 
 
 Cpos. est. ion = **/*' X C esU , X C H (i l) 
 
 and have 
 
 dx/dt = K v(ion) X k aff jk' X C ester X C H X [C H X C OH ] (12) 
 
 = K v X C ester X C H X C H X C OH (13) 
 
 which is the ordinary equation representing the velocity of decomposition 
 of esters by acids. What we determine with esters, for instance in Hemp- 
 tinne's and Lowenherz's work as expressed in Table III is K v and not 
 the more fundamental constant K V (i on ). Now 
 
 K v = K,(M X hrfjk' (14) 
 
 and it is obvious that if the basic strength of the ester as expressed in 
 k a ff. grows very much smaller, as it undoubtedly does when we go from 
 ethyl acetate to ethyl chloroacetate, K V (i on ) could easily grow very much 
 larger and yet K v need not change appreciably or it might even grow smaller, 
 without the result being in any disagreement whatever with the theory 
 expressed. This means, of course, that determinations simply of the 
 velocity constants K v of decomposition of such esters do not prove any- 
 
 1 The table is taken from Euler, Loc. tit., p. 412. 
 
 2 Stieglitz, International Congress of Arts and Science, St. Louis, 1904, 4, 276 
 of the report, and Am. Chem. J., 39, 47 (1908). 
 
 8 C pos . est . ion is a function of x. 
 
 4 k' is the stability constant of the oxonium hydroxide. k a ftjk' may be considered 
 the stability constant of the complex ester ion. Cf. Bredig, Z. Elektrochem., 9, 118 
 (foot-note). 
 
 38 
 
ORGANIC AND BIOLOGICAL. 228 
 
 thing as to the principle at issue. A somewhat stronger base might 
 well give a higher rate of change than a weaker one by virtue of the fact 
 that a larger proportion of the base is present in its active form, the ion, 
 and the real rate of decomposition of the ion may be much smaller than 
 that of an ester giving a smaller velocity constant K v . The imido esters 
 have the advantage that their affinity constants are easily ascertained 
 and we do not deal with any such unknown quantity at all, and thus we were 
 able to bring what I believe is the first experimental proof of the sound- 
 ness of the theory. An apt illustration of the correctness of our argu- 
 ment concerning the lack of data for a correct analysis of results like those 
 given in Table III is found in the following facts: the formation of ami- 
 dines from imido esters, as was stated, is greatly accelerated by the addition 
 of acids or of an ammonium salt and we were able to show that the amidine 
 formation may be considered essentially a function of the concentration 
 of the positive ester ion, proceeding according to 
 
 C 6 H 5 C< + NH 3 > C 6 H 5 C< + HOCH, (9) 
 
 X 
 
 OCH 3 
 and 
 
 dx/dt = K V X C pos _ est . ^ X C NHt 
 
 Now, if we develop the expression for the concentration of the positive 
 ion of a very weak base like an imido ester in the presence of a much 
 stronger one like ammonium hydroxide we find that: 
 
 .. , 
 
 *~NH 3 K off. amm. 
 
 and by substitution we get: 
 
 fir I rlt - K V kaff - est - V CesUr X CNH * + V 
 
 ax/at - K v(ion ) X , X 
 
 K aff. amm. 
 
 - a ft- est - / 
 
 a/7. amm. 
 
 Now, imido ethyl benzoate forms benzamidine considerably faster 
 than does the methyl ester: in both cases the change is from the salt of 
 the positive ion of a weaker base to that of a much stronger one, the 
 amidine, but the ethyl ester is the stronger base and yet it reacts the faster 
 and apparently contradicts our theory. A knowledge of the affinity 
 constants shows, however, that it reacts the faster only because by virtue 
 of its being a stronger base it takes a larger proportion of the catalytic 
 agent, the acid, from the ammonium chloride, and forms a proportionally 
 larger concentration of the active component, the ester ion, than does 
 the methyl ester under the same conditions. Calculating with the aid 
 
 1 Cpos. est. ion is a function of x. 
 
 2 In passing, it may be remarked that this last form shows that the action may be 
 considered one of the ion ammonium acting on the ester, but we believe our original 
 assumption to be the right one for reasons found in the behavior of organic compounds 
 which cannot be elaborated here ; it may be said, for instance, that we have found NH, 
 and not NH 4 + to react with ordinary esters to form amides and are carrying out other 
 more crucial experiments on this point. Vide Acree, Am. Chem. J., 38, 308. 
 Fitzgerald and Lapworth, /. Chem. Soc., 93, 2163. 
 
 39 
 
229 CATALYSIS ON THE BASIS OF WORK WITH IMIDO ESTERS. 
 
 of the affinity constants the true velocities of transformation of the positive 
 ions, we find the true relation: ^(ion) for the methyl ester is 140/0.434 
 and for the ethyl ester only 69/0.434. * So the true relations resulting 
 from an exact knowledge of all the quantitative constants involved agree 
 perfectly with the fundamental principle given. 
 
 This reaction shows other points of great interest: for instance, the fact 
 that the concentration of ammonia cancels out of the mathematical 
 equation leads to the conclusion that the velocity of decomposition is 
 independent of the concentration of ammonia, one of the reacting com- 
 ponents. 
 
 This peculiar conclusion has been fully verified by experience; the 
 velocity constant is as a matter of experiment almost, although not ab- 
 solutely, independent of the concentration of ammonia ; in the case of the 
 above methyl ester, the constant grows only about 10 per cent, with an 
 increase of 400 per cent, in the concentration of the ammonia. This ap- 
 parent contradiction with the law of mass action is readily understood 
 if we remember that the concentration of ammonia has two effects which 
 oppose each other; ammonia does accelerate the action in proportion to 
 its mass as required by the law, but it also to the same degree retards 
 the action by depriving the weaker base of the ionizing and therefore 
 catalyzing acid. Within a year Lapworth 2 has made the extremely 
 important discovery that water stands in exactly the same relation to 
 the esters in the catalysis by acids only then the two bases competing 
 for the acid are two oxonium bases, the ester and water. 
 
 And now in conclusion I wish to call attention to one more result with 
 these imido esters which has impressed us very much and which seems 
 to me to throw a very clear light on the whole question of catalysis or 
 acceleration by showing certain limitations to catalytic effects. It was 
 mentioned a moment ago that the velocity of formation of benzamidine 
 from methyl imido benzoate may be expressed as a function of the positive 
 imido ester ion and that it is almost independent of the concentration of 
 the ammonia; but it is not absolutely independent, there is a slight but 
 steady rise in the value of the constants with increasing concentrations 
 of ammonia. All other secondary reactions having been excluded (e. g., 
 for fourfold increase of NH 3 , the constants rise gradually from 139/0.434 
 to 154/0.434) as the cause of this increase by a knowledge of their velocity 
 constants, we suspected that besides the main action of ammonia on the 
 positive ester ion, there is a much slower action of ammonia also on the 
 non-ionized free ester, namely, that we have two simultaneous actions: 
 C 8 H 6 C( : NH 2 +)OCH, + NH, + C e H 6 C(' : NH 3 +)NH 2 + HOCH, (18) 
 
 and 
 
 C 6 H 6 C( : NH)OCH, + NH S > C 8 H 5 C( : NH)NH 2 + HOCH, (19) 
 We had the more reason to suspect this as we had already found that 
 water, besides decomposing the positive ion of an imido ester at a very 
 high speed, also undoubtedly decomposes the non-ionized ester at a very 
 slow rate. 8 It was found that the experimental results agree very well 
 with this conception of two simultaneous actions in the formation of 
 
 1 Miss Katharine Blunt's dissertation (1907). 
 
 2 Loc. cit. 
 
 * In this case the products are different. Vide Stieglitz, Derby and Schlesinger, 
 Loc. cit. 
 
 40 
 
ORGANIC AND BIOLOGICAL. 230 
 
 benzamidine and that the velocity constant for the action of ammonia 
 on the positive ester methyl ion at 25 is 325, while that on the ester 
 molecule is only 0.0069. * That is, the positive ion is almost 50,000 times 
 as reactive as the non-ionized molecule. It may appear somewhat 
 surprising that such a small constant could still be detected side by side 
 with such an enormous one, the whole action being completed in one 
 to two hours. But we must remember that for the ion action with the 
 enormously high rate of change we have at any moment only minute 
 quantities of the reacting component, e. g., 0.000,005 gram ion at the 
 beginning of a velocity measurement, which is used up at an enormous 
 speed but always formed again instantly by the purely ionic action of 
 imido ester on the ammonium chloride. On the other hand the transfor- 
 mation of the non-ionized molecule has the advantage of relatively high 
 concentrations of each of the reacting components, say 0.05 both for the 
 ammonia and for the free ester at the beginning of an action. With a 
 concentration many thousand times in its favor it is then not surprising 
 to find this very slow action becoming perceptible in careful quantitative 
 work. Now, if we should use a much weaker base still, we might easily 
 find the action with the non-ionized ester taking a more and more promi- 
 nent part in the total change, even if the actual rate of change of the 
 positive ester ion should still be very much the greater. We have recently 
 found such to be the case for the action of ammonia and ammonium 
 chloride on benzoyl urea ester: 2 the velocity constants are so nicely 
 balanced against the affinity constants that the observed changes did not 
 agree even approximately with either conception used alone, viz., that 
 the guanidine formation was due to the action of ammonia on the positive 
 ester ion alone, or on the non-ionized ester alone. But they did agree 
 well with the view that both actions occur simultaneously, the velocity 
 coefficient for the action on the ion being 34.5 and the coefficient for the 
 action on the non-ionized ester being 0.0015, a ratio of 23000 to i again. 
 We were exceedingly pleased to find this case because it forms the con- 
 necting link with what we have found to be true for the formation of 
 ordinary acid amides from acid esters in the presence of ammonia and 
 ammonium salts: 
 
 CH 3 COOCH 3 + NH 3 -> CH 3 CONH 2 + HOCH 3 (20). 
 
 This action seems to be essentially a function of the ester and ammonia 
 and it is an extremely slow reaction. 3 We can easily understand this 
 case now; the esters as extremely weak oxonium bases must be able to 
 take only the faintest traces of acid from the ammonium chloride in the 
 presence of ammonia and therefore the slow molecular transformation 
 comes to the front as enormously favored by the concentrations of the 
 reacting components. In the case of the actions of acids on esters and 
 water, the esters compete only with an oxonium base of the same order 
 of strength as they are themselves and rather weaker, 4 the oxonium base 
 of water and here the reaction with the ion is again predominant. 
 
 These studies then show us a whole range of organic compounds, obvi- 
 ously of the same type and family but giving reactions which proceed quite 
 
 1 Mr. Norton is collecting more data on these relations. 
 
 1 J. C. Moore's dissertation (1909). 
 
 * Unpublished work by J. Stieglitz and Dr. Barnard. 
 
 4 Lap worth, Loc. cit. 
 
 41 
 
231 ON THE BIOCHEMISTRY OF NUCLEIC ACIDS. 
 
 differently with the imido esters the action of ammonia on the positive 
 ion is the essential action and the use of a catalytic agent, 1 an acid is 
 advisable, in fact, necessary ; with ordinary esters the action on the ion 
 becomes negligible because the ion simply cannot be produced in sufficient 
 quantity under these conditions and the action of ammonia on the non- 
 ionized ester becomes the essential action. The addition of acid as a catalytic 
 agent is practically ineffective and therefore inadvisable. But these ap- 
 parently disconnected results are now easily understood as being per- 
 fectly consistent and logical the one case representing an almost but 
 not quite pure type of one of the two natural simultaneous reactions 
 the enormously rapid action of the ammonia on the imido ester ion and 
 the other case representing the almost pure type of the other simultaneous 
 action, the extremely slow action of ammonia on the non-ionized ester 
 molecule. And the connecting link is found when the adjustment of 
 the affinity and the velocity constants involved bring both actions out 
 prominently at the same time. Of course one must then expect every 
 possible class of reactions lying between these extremes. The results 
 show plainly then, I believe, why a catalytic agent will work smoothly 
 in a number of cases, and why it will fail utterly in accelerating actions 
 apparently of exactly the same organic type, differing only in the numer- 
 ical value of the physico-chemical constants included in the final expres- 
 sion governing the action of a catalytic agent. We have been using the 
 imido esters simply as a kind of magnifying glass to measure all these 
 constants and thus to enable us to recognize some of the general underly- 
 ing principles which govern catalysis by such chemical agents, as acids, 
 bases and salts. 
 
 ON THE BIOCHEMISTRY OF NUCLEIC ACIDS. 2 
 
 BY P. A.' LEVENE. 
 Received December 2, 1909. 
 
 Life is the most complex phenomenon in nature and its manifesta- 
 tions are innumerable. They all mysteriously arise in the living organism 
 and are all harmoniously centered in it. This, even in its simplest form 
 is the most perfect laboratory, the seat of an infinite number of chem- 
 ical reactions, none of them interfering with the equilibrium of the others. 
 The substances produced by the most primitive of the living organisms 
 are as large in number as they are varied in their properties. The dis- 
 coveries of new substances manufactured by the plant or animal cell 
 are not yet exhausted and for ages the chemist dreamed of no better 
 reward for his labors than the finding in tissue juices of a new body with 
 properties hitherto unknown. The living organism was the only retort, 
 vital force the only reaction in his possession that could furnish him with 
 carbon-containing substances. In that sense every chemist in those 
 days was a biological chemist. 
 
 In the year 1828 a startling discovery was announced. Wohler wrote 
 to Berzelius: "I must tell you that I can make urea without the aid of 
 the kidney, or generally without the living organism whether of man 
 or dog," and four years later the divorce of biological and organic 
 
 1 Loc cit. 
 
 3 Presented at the Second Decennial Celebration of Clark University, Worcester, 
 Mass., September 15, 1909. 
 
 42 
 
ORGANIC AND BIOLOGICAL. 232 
 
 chemistry was apparently accomplished when Wohler and Liebig laid 
 the foundation of the organic chemistry of to-day by their work on the 
 radicle of benzoic acid. However, the divorce was only apparent, for 
 the reason that only the knowledge of molecular constitution made it 
 possible to establish the relationship between the organism and the 
 chemical bodies manufactured by it, only the knowledge of the dynamics 
 of the chemical reactions could coordinate the observations of the func- 
 tions of the living organism, and of the accompanying changes in the 
 composition of the living cells. 
 
 The attitude of the biological chemist was altered. He saw his new 
 goal in disclosing the nature of chemical reactions occurring within the 
 living cell and finding their bearing on the manifestations of life. 
 
 If time permitted I would present to you the progress of all the work 
 done in that direction in recent years. Within the narrow limits of this 
 report, however, this is impossible to accomplish with any degree of 
 justice to the subject and I shall, therefore, limit the discussion to only 
 one phase, namely, to the work bearing on the chemical interpretation 
 of one of the most cardinal properties of living matter. 
 
 Living matter is distinguished from inanimate by the fact that it under- 
 goes cleavage and oxidation at a very perceptible velocity, and that 
 the restoration of the loss sustained in that manner takes place at approx- 
 imately the same rate. Thus the function of automatic regeneration 
 lends to living matter its principal peculiarity. 
 
 Great credit is due to the biologist for the discovery that in an or- 
 ganized cell this function is seated in a formation possessing definite 
 chemical properties, named chromatin or nuclein. At a time when 
 the process of regeneration is very active, namely, during the develop- 
 ment of the fertilized egg, the rate of the new formation of nuclein rises 
 to a very perceptible degree, and the observer is led to see a genetic re- 
 lationship between these two processes. 
 
 Our distinguished biologist, Jacques L/oeb, 1 was the first to express 
 the function of reproduction in terms of chemical reactions. In his 
 address to the International Congress of Zoologists held in Boston in 
 September, 1907, he stated: "If the question be raised as to what is the 
 mo t obvious chemical reaction which the spermatozoan causes in the 
 egg, the answer must be an enormous synthesis of chromatin or nuclear 
 material from constituents of the cytoplasm." Thus, it becomes evident 
 that the knowledge of the mechanism of regeneration is dependent on the 
 knowledge of the chemistry of nucleins. 
 
 I shall for a moment forestall the systematic discussion of the chemical 
 nature of nucleins by mentioning that at the time of Loeb's address we 
 were in possession of considerable information on the composition of 
 these substances. It was known that phosphoric acid entered into the 
 formation of the molecule. Therefore, it became evident to Loeb that 
 a supply of phosphoric acid was required in order to make a synthesis 
 of nucleins possible. In a developing egg the phosphoric acid was fur- 
 nished by the cell itself, for the formation of nucleins proceeded also 
 when the eggs were placed in a medium free of phosphoric acid. The 
 other components of the cell that are known to contain phosphoric acid 
 in their molecule are the lipoids. In these substances phosphoric acid 
 
 1 University of California Publications in Physiology, 3, 61-81 (1907). 
 
 43 
 
233 ON THE BIOCHEMISTRY OP NUCLEIC ACIDS. 
 
 is present in an ester-form combination, and Professor Loeb proceeded 
 to argue that the first phase in cell reproduction a priori ought to consist 
 in the saponification of its lipoids. This assumption was brilliantly verified 
 in his experiments on artificial parthogenesis. He brought to light the 
 fact that dissolution of the lipoids is actually the process which precedes 
 the nuclein synthesis and the segmentation of the nucleus. He further 
 demonstrated that agencies facilitating this saponification were able under 
 favorable conditions to start the development of an unfertilized egg 
 without the aid of spermatozoa. Thus only an elementary knowledge 
 of the chemical nature of two cell components furnished Professor Loeb 
 with the power at will to start or to impede cell development by chemical 
 means, and in a way to furnish evidence that the function of regeneration 
 was a chemical process. But the process of nuclein synthesis in the ac- 
 tive cells is not yet disclosed in its harmonious entirety, and no one can 
 entertain any hope of arriving at this knowledge without the discovery 
 of the chemical constitution of nudeins. 
 
 The considerations that attracted the attention of so many chemists 
 to the work on the chemical nature of these substances, therefore, are 
 becoming very obvious, and I shall attempt to present the results and the 
 achievements of the numerous endeavors towards the solution of this 
 very difficult problem. 
 
 The first important contribution to the chemistry of nucleins was 
 made by Altman, a biologist. 1 Altman was in possession of the infor- 
 mation that nucleins were endowed with the properties of fairly strong 
 acids, and further that they were quite resistant to the action of pepsin 
 hydrochloric acid. The latter property enabled him to prepare con- 
 siderable quantities of nuclein by removing the protein part of the tis- 
 sues by means of peptic digestion, and the fats by the usual extractives. 
 The remaining nuclein he found to consist of a protein combined with 
 a conjugated phosphoric acid. The acid he named "nucleic acid." 
 By means of alkaline hydrolysis, Altman succeeded in removing all the 
 protein from his nuclein so that the final product analyzed by him re- 
 fused to disclose any trace of protein even by the aid of the most sensitive 
 color test. 
 
 The further development of the chemistry of nucleic acid was accom- 
 plished through the investigations of Miescher, of Schmiedeberg and his 
 pupils, of Kossel and his school, by Haiser, G. H. Hammarsten and his 
 pupil Ivar Bang, and in this country by the work of T. B. Osborne, of 
 Walter Jones, and of my co-workers and myself. I must, however, add 
 that the purest nucleic acid was obtained by the man who was first in 
 so many lines of chemical activity, Liebig, although on this occasion 
 he failed to discover the real significance of his finding. 
 
 I shall make no attempt to present all the work on nucleic acid in its 
 chronological order, but I shall refer to individual investigations in con- 
 nection with the discussion of the development of the various phases in 
 our knowledge of chemical structure of those complex acids. 
 
 The three principal phases in the endeavors to reveal the nature of 
 nucleic acid consist: first, of work aiming to obtain the substance in a 
 convenient manner, and in a possibly unaltered condition with a 
 
 1 Arch. Anat. und Physiol. Physiol. Abt., 1889, 524. 
 
 44 
 
ORGANIC AND BIOLOGICAL. 234 
 
 view to ascertain the elementary composition of the substance; second, 
 in the work directed towards finding all the components of the various 
 nucleic acids ; and third, in determining the actual structure of the molecule ; 
 or in other words the manner of arrangement of the individual com- 
 ponents within the molecule. 
 
 Ultimate Analysis of Nucleic Acids. 
 
 I shall touch only briefly on the first phase of the work, for the reason 
 that it is of interest principally to the men personally engaged in it. The 
 achievements obtained through that work are not very significant. Only 
 in connection with the study of inosinic acid, a nucleic acid of beef muscle, 
 the elementary analysis was of unmistakable service in ascertaining the 
 composition of the substance. It was the first and thus far the only 
 instance that a salt of a nucleic acid was obtained in a crystalline form. 
 The fact that no other nucleic acid has been prepared in an absolutely 
 pure condition renders the conclusions drawn from their analysis only 
 of secondary value. The workers who contributed to the improvement 
 in the methods of preparation of the substance are: Altman, Miescher, 
 Schmiedeberg, Kossel, Neumann, Hammarsten, Bang, Haiser and myself. 1 
 
 The methods of preparation and of purification of the substance 
 employed by individual workers differed greatly either in principle or 
 detail. Under such circumstances marked divergence was noted in 
 the analytical figures obtained by different investigators for nucleic acids 
 even of the same origin. The following table illustrates some of these 
 discrepancies. 
 
 TABLE SHOWING THE ELEMENTARY COMPOSITION OP VARIOUS NUCLEIC ACIDS. 
 
 C. H. N. P. O. Base. 
 
 I. Thymonucleic acids of animal 
 origin: 
 
 1 Fisch sperm: 
 
 a Salmon (Miescher and 
 
 Schmiedeberg) 37.8 4.5 15.8 9.7 33.2 
 
 b Gadus (Levene) 34.8 5.2 16.8 9.1 
 
 c Homo (Katsuji and 
 
 Inouye) 37.5 4.4 16.0 9.7 
 
 d Maifisch (Levene and 
 
 Mandel) 36.3 5.0 15.9 8.1 
 
 2 Pancreas: 
 
 a Ivar Bang 34.2 4.4 18.2 7.7 35.6 
 
 b v. Furth, and Jerusalem. .. 29.2 4.3 u.6 6.9 ... Cu = 14.2 
 
 3 Spleen (Levene) 37.8 4.8 16.5 8.99 
 
 4 Mammary gland (Levene and 
 
 Mandel) 34.7 4.4 15.6 8.5 
 
 5 Intestinal wall (Katsuji Inouye) 37.5 4.8 15.5 9.4 
 
 6 Thymus gland: 
 
 a (Ivar Bang) 35.8 4.2 15.3 9.3 ... Na 6.25 
 
 1 Altmann, "Uber Nukleinsauren," Arch. /. Anat. u. Physiol. Physiol. Abt., 1889, 
 524. Miescher, Verhand. der naturforschenden Ges. in Basel, 1874, 6, 138; Arch. exp. 
 Path. Pharm., 37, (1896). Schmiedeberg, Arch. exp. Path. Pharm., 43, 57 (1900). 
 Kossel u. Neumann, Ber., 27, 2215, (1894), Neumann, Arch. Anat. und Physiol. Physiol. 
 Abt., 1899, 552. Bang, Z. physiol. Chem., 26, 133 (1898-9). Haiser, Monatsh. Chemic, 
 16. Levene, Z. physiol. Chem., 32, 541 (1901); 37, 402 (1902-3); 45, 370 (1905). 
 
 45 
 
235 ON THE BIOCHEMISTRY OF NUCLEIC ACIDS. 
 
 C. H. N P. O. Base. 
 
 b (Kostytschew) 3* -4 4-6 12.8 7.6 ... Ba 17.5 
 
 c (Herlant) 37-534-9316.489.63 
 
 d (Schmiedeberg) 35.82 4. 14 14.68 9. 17 
 
 II. Guanylic acid (animal origin): 
 
 a Ivar Bang 34 .28 4.39 18.21 7.64 34.48 
 
 b Levene and Mandel 36.35 4.95 18.65 6.15 33.90 
 
 III. Plant nucleic acid: 
 
 1 Yeast: 
 
 a Herlant 337 4.1 14.8 8.69 ... Cu 10 
 
 b Levene 34-97 4-4* 15.21 8.6 
 
 2 Wheat embryo (Osborne and 
 
 Harris) 33.1 4.2 14.9 8.1 
 
 In adopting an empirical formula for the nucleic acids the individual 
 investigators were guided not only by the analytical figures, but also by 
 considerations of a speculative nature based to some extent on information 
 obtained on partial or complete hydrolysis of the acids. The basis for 
 the speculations of the different workers varied considerably. This 
 led to a great divergence in the views on the empirical formula of nucleic 
 acid. The following table contains some illustrations of it: 
 
 c. H. N. o. P. 
 
 Schmiedeberg 1 (spermnucleic acid) 40 56 14 26 4 
 
 Stetidel 2 (thymus nucleic acid) 43 57 15 26 4 
 
 [54 71 20 37 5 
 
 Levene 3 (spleen nucleic acid) 
 
 {43 55 15 3i 4 
 
 Osborne and Harris 4 (wheat embryo nucleic acid) 42 62 16 31 4 
 
 117 26 6 14 2 
 
 Kossel 5 (yeast nucleic acid) . 
 
 25 36 9 20 3 
 
 Boas* (yeast nucleic acid) 36 52 14 24 4 
 
 Levene 7 (yeast nucleic acid) 38 50 15 29 4 
 
 The Components of Nucleic Acids. 
 
 It has been stated that the first knowledge of the chemical nature of 
 nucleic acids was limited to the information that it was a conjugated 
 phosphoric acid. The first work of Altmann was followed by that of 
 Kossel. The efforts of this investigator were directed towards the analysis 
 of the products of hydrolytic cleavage of nucleic acids. His first achieve- 
 ment was the discovery of purine bases in the molecule of nucleic acids. 
 These bases can be obtained on cleavage of nucleic acids with very dilute 
 solutions of mineral acids. Kossel further devised methods for the 
 separation of the individual bases. He arrived at the conclusion that 
 four purine bases, namely, adenine, guanine, hypoxanthine and xanthine, 
 enter into the molecule of nucleic acids. This view, however, was later re- 
 vised as it was established that only two purine bases, adenine and guanine, 
 actually enter into the composition of nucleic acids. Hypoxanthine and 
 
 1 Arch. exp. Path. Pharm., 57, 309 (1907). 
 
 2 Z. physiol. Chem., 46, 332 (1905). 
 8 Biochem. Z., 17, 120 (1909). 
 
 4 Z. physiol. Chem., 36, 85 (1902). 
 ' Arch. f. Anat. Physiol., p. 181 (1891). 
 Arch exp. Path. Pharm., 55, 16 (1906). 
 7 Biochem. Z., 17, 120 (1909). 
 
 46 
 
ORGANIC AND BIOLOGICAL. 236 
 
 xanthine are now regarded as secondary products. 1 However, it was 
 evident from the figures obtained on elementary analysis of nucleic acids, 
 that their molecule contained substances other than purine bases. On 
 the basis of the observation that on hydrolysis with dilute mineral acids 
 only the purine bases are liberated and the other components remain 
 intact, there was advanced a theory that in nucleic acids the phosphoric 
 acid is combined with a complex radicle forming a conjugated phosphoric 
 acid, and that this in its turn combined with the purine bases. The 
 manner of this combination was the subject of considerable discussion 
 and disagreement. 
 
 The efforts to elucidate the composition of the complex radicle resulted 
 in the discovery of the following purine derivatives. 2 
 
 N = C.NH 2 HN CO HN CO 
 
 OC CH OC CH OC C.CH 3 
 
 I II I II I II 
 
 HN CH HN CH HN CH 
 
 Cytosine. Uracil. Thyinine. 
 
 However, in order to obtain these substances it was necessary to resort 
 to the hydrolysis by means of mineral acids of considerable concentra- 
 tion. This procedure caused many investigators to express doubt as 
 to the presence of the pyrimidine bases in the nucleic acid molecule. 
 The doubt was particularly great regarding the orgin of cytosine and 
 uracil. R. Burian 3 with great persistence defended the view that these 
 two bases took their origin in the partial cleavage of the purine ring. 
 However, the majority of workers were inclined to consider cytosine 
 also as a primary constituent of the molecule of nucleic acids, while uracil 
 was considered a primary product in the acids of plant origin only. 
 
 Besides the purine and pyrimidine bases the molecule of nucleic acid 
 was found to contain carbohydrates. The complex nucleic acids of 
 animal origin contain a hexose, the exact nature of which is not yet 
 established. The nucleic acid of plant origin and the simpler nucleic 
 acid of the animal tissues contain a pentose. On the basis of the work 
 of Neuberg 4 the pentose was considered /-xylose. However, very recently 
 Jacobs and I have succeeded in isolating the substance in crystalline form. 
 This made it possible to establish the true nature of the substance as 
 d-ribose. 5 
 
 As the methods of analysis had improved, and as approximately quan- 
 titative estimation of the components was made possible, it was found 
 that in nearly all the acids the bases were present in approximately 
 equimolecular proportions, that the number of molecules of phosphoric 
 
 1 Levene, Z. physiol. Chem., 45, 370 (1905). W. Jones and Austrian, J. Biol. Chem., 
 3, i (1907). 
 
 2 Kossel and Neumann, Ber., 27, 2215 ( J 894). Ascoli, Z. physiol. Chem., 31, 161 
 (1900-1). Kossel and Steudel, Ibid., 37, 177 (1902-3). Levene, Ibid., 37, 402, 527 
 (1902-3). 
 
 * R. Burian, Ergebnisse der Physiol. 3 Jahrg. i Abt., 98 (1904); Z. physiol. Chem., 
 51, 438 (1907). Steudel, Z. physiol. Chem., 53, 508 (1907). Osborne and Heyl, Am. J. 
 Physiol., 20, 157 (1908). Levene and Mandel, Biochem. Z., 9, 233 (1908). 
 
 4 Neuberg, Ber., 32, 3386 (1899). 
 
 Levene and Jacobs, Ibid., 42, 2102, 3247 (1909). 
 
 47 
 
237 ON THE BIOCHEMISTRY Of NUCLEIC ACIDS. 
 
 acid corresponded to that of the bases, and the number of molecules of 
 carbohydrate was equal to that of phosphoric acid. 1 
 
 On the basis of these calculations, and on the basis of the numbers of 
 the character of the bases entering into the molecule of the individual 
 nucleic acids the following classification could be established: 
 
 1. Nucleic acids: Containing one purine base (no pyrimidine), a pen- 
 tose and phosphoric acid. (Inosinic acid, guanylic acid.) 
 
 2. Nucleic acids: Containing two purine bases (guanine and adenine), 
 two pyrimidine bases (cytosine and uracil) and phosphoric acid. (Phy to- 
 nucleic acids.) 
 
 3. Nucleic acids: Containing two purine bases (guanine and adenine), 
 two pyrimidine bases (thymine and cytosine), and a hexose and phos- 
 phoric acid. (Nucleic acid of animal tissue thymonucleic acids.) 
 
 The Constitution of Nucleic Acids. 
 
 The early speculations regarding the constitution of nucleic acids were 
 based on the results of partial hydrolysis by means of dilute acids or 
 weak alkalies. Reference has been made already to the views expressed 
 by Kossel. 2 By mere heating with water under increased pressure, this 
 author thought he obtained a substance, which was free of purine bases, 
 but contained all the other components of the original nucleic acid. The 
 substance was named thymic acid. Nucleic acid was regarded therefore 
 as a complex consisting of thymic acid and of purine bases. The author 
 did not furnish any detailed information regarding the nature of thymic 
 acid. Somewhat more definitely formulated was the view of Schmiede- 
 berg. According to this author there existed a complex nucleotin, this 
 complex combined with phosphoric acid to form nucleotin phosphoric acid, 
 and this acid in its turn combined with purine bases thus forming nucleic 
 acid. Schmiedeberg ascribed to the nucleotin the formula C 30 H 42 N 4 O 1S . 
 Alsberg, 3 working in Schmiedeberg's laboratory, actually succeeded in 
 obtaining a substance which had the composition of the hypothetic 
 nucleotin. However, these writers also failed to disclose the constitution 
 of the complex radicle. In fact, they failed to furnish evidence that 
 their substance was not a mixture composed of several cleavage products 
 of nucleic acids. 
 
 Results of actual significance for the interpretation of the structure 
 of the nucleic acid were obtained only recently. The point of de- 
 parture for the work was the study of inosinic acid by Levene and Jacobs. 
 As has already been pointed out this acid is comparatively simple in its 
 composition. It is composed of phosphoric acid, a pentose and hy- 
 
 1 Schmiedeberg, Arch. exp. Path. Pharm., 46, 57 (1900). Kossel u. Neumann, 
 Ber., 27, 2215 (1894). Kossel u. Steudel, Z. physiol. Ckem., 37, 119, 120, 121, 131, 
 177 (1902-3); 145, 377 (1903); 38, 49. Ascoli, Ibid., 31, 161 (1900-1). Steudel, 
 Ibid., 42, 165 (1904); 43, 402 (1905); 44, 157 (1905); 46, 332 (1905); 48, 425 (1906). 
 Osborne and Harris, Ibid., 36, 85 (1902). Jones, W., and Austrian, /. Biol. Chem., 3, 
 i (1907). Levene, Z. physiol. Chem., 37, 402, 527 (1902-3); 38, 80 (1903); 39, 4, 479 
 (1903); 43, 199 (1904); 45, 37 (1905)- Levene and Stookey, Ibid., 44, 404 (1904). 
 Mandel u. Levene, Ibid., 46, 155 (1905); 47, 140 (1906). v. Furth u. Jerusalem, Beitrage 
 Chem. Physiol. u. Pathol., 10, 174 (1907). 
 
 1 Kossel and Neumann, Z. physiol. Chem., 22, 74 (1896-7). 
 
 3 Schmiedeberg, Ach. exp. Path. Pharm., 43, 57 (1900). Alsberg, Ibid., 51, 239 
 '1904). 
 
 48 
 
ORGANIC AND BIOLOGICAL. 238 
 
 poxanthine. Through prolonged action of dilute acid at the temperature 
 of 50 it was possible to break up the molecule into hypoxanthine and 
 a pentose-phosphoric acid. 1 This substance was obtained by Jacobs 
 and myself in the form of its crystalline barium salt. This acid had all the 
 properties of a conjugated phosphoric acid, and on cleavage yielded the 
 phosphoric acid. The acid reduced Fehling's solution on heating without 
 previous hydrolysis. It was concluded from this that in the molecule 
 the phosphoric acid and the carbohydrate are bound in ester-form, and 
 that the aldehyde group of the pentose phosphoric acid was free and that 
 therefore in the inosinic acid the base and pentose were coupled in a gly- 
 coside union. This assumption was strengthened by the fact that 
 inosinic acid was found to be very resistant towards the action of alkalies 
 even at fairly high temperatures, and even on prolonged boiling the 
 acid underwent only partial hydrolysis with formation of phosphoric 
 acid and of the complex: pentose-base. Furthermore, it was found that 
 by hydrolysis at nearly neutral point the conditions for the reaction 
 were more favorable and it was possible in this manner to isolate and to 
 identify the pentoside-inosine (C^H^N^). On the basis of this we 
 concluded that the order of combination of the components in the 
 molecule of the inosinic acid was established. I could add here that 
 only on hydrolysis of the pentoside was it possible to obtain the crystal- 
 line sugar which was identified as d-ribose. The structure of the com- 
 plex pentose-hypoxanthine may be represented in the following manner: 
 
 N C N 
 
 II II I 
 HC 
 
 H H H H | 
 
 CH 2 OH C C C C N C CH 
 | OH OH | || 
 
 L O OC NH 
 
 The same substance had been found by Haiser and Wenzel in beet 
 extract. 2 
 
 Regarding the place of the purine base which entered into union with 
 the sugar, there still remains only the evidence of Burian that place 7 
 is attached to the sugar and no information exists regarding the place 
 of the hydroxyl in the pentose that is coupled with the phosphoric acid. 
 The following step in the progress of the work was the application of 
 the experience obtained on inosinic acid to the other nucleic acids. Jacobs 
 and I next directed our attention to the remaining acid of comparatively 
 simple composition, namely guanylic acid. Employing the same methods 
 of hydrolysis as applied to inosinic acid, we obtained guanosine 
 (C 10 H 13 N 5 O 5 ), a substance analogous to inosine; it possessed nearly the 
 same crystalline form, differed in its physical constants, and on hydrolysis 
 gave guanine and the same pentose as the inosine, namely d-ribose. This 
 pentoside had the same properties as inosine in its behavior towards al- 
 kalies and acids. 3 For the sake of convenience we named the substances of 
 this order " nucleosides " and the combination of the nucleoside and phos- 
 phoric acid we named "nucleotides." Thus according to that nomencla- 
 1 Ber., 44, 2703 (1908). 
 
 1 Haiser and Wenzel, Monatsh. Chem., 29, 157 (1908) 
 Ber., 42, 2474 (1909). 
 
 49 
 
239 
 
 ON THE BIOCHEMISTRY OF NUCLEIC ACIDS. 
 
 ture inosine and guanylic acid were to be regarded as mononucleotides of 
 the following structure : 
 
 N C N 
 
 X)H 
 
 CH 
 
 H H H H l| 
 
 O = P O CH 2 C C C C N C CH 
 
 
 OH 
 
 OH OH 
 i o 
 
 (Inosinic acid.) 
 
 H H H H 
 
 OC NH 
 
 N C N 
 
 !! II II 
 CH 
 
 O = P O CH 2 C C C C N C C (NH 2 ) 
 
 \ 
 
 OH 
 
 OH OH 
 
 (Guanylic acid.) 
 
 OC NH 
 
 The further application of the same methods to a more complex nucleic 
 acid, to that of the yeast, led to the conviction that this also was com- 
 posed in the same manner. Thus the same nucleoside-guanosine, as 
 obtained from guanylic acid, was also found on hydrolysis of the yeast 
 nucleic acid. When the proper conditions are observed the nucleoside 
 can be chilled out and a nearly quantitative separation accomplished. 
 In the filtrate from this nucleoside other substances of the same nature 
 were expected. On the basis of considerations expressed by me in an 
 earlier article on the composition of the yeast nucleic acid the molecule 
 of the acid is composed of four nucleotides and therefore four nucleosides 
 should be found on cleavage of the substance. The work in that direc- 
 tion is of comparatively recent date, and a second nucleoside has already 
 been obtained from the mother liquor of guanosine. 1 The second nucleo- 
 side has practically the same crystalline appearance as inosine or guano- 
 sine, and differs from these two only by its physical constants and by 
 the fact that on hydrolysis it yields in place of guanine the base adenine, 
 and is, therefore, named adenosine. Also on hydrolysis of this nucleo- 
 side the crystalline d-ribose is obtained. The substance therefore had 
 the following structure : 
 
 N C N 
 
 CH 
 
 H H H H 
 
 CH,OH C C C C N C CH 
 
 OH OH 
 
 NH,C = N 
 
 It possesses the melting point of 229 and the rotation: [a] D = 67.30. 
 On the ground of this the structure of the yeast nucleic acid may be 
 presented in the following manner : 2 
 
 1 Levene and Jacobs, Ber., 42, 2703 (1909). 
 
 2 Bloch, Zeitsch., 120, 17 (1909). 
 
ORGANIC AND BIOLOGICAL. 
 
 240 
 
 OH H H H 
 
 O = P O CH 3 C C C CH C 6 H 4 N 5 
 | OH OH | 
 
 O J O 
 
 H H H 
 
 O = P CH, C C C CH C 5 H 4 N 5 O 
 | OH OH |! 
 
 OH J O 
 
 All this work is of comparatively recent date so that as yet it could 
 not have been extended to the analysis of thymonucleic acid. But 
 evidence had been furnished that this substance also has a structure 
 analogous to that of the yeast nucleic acid. 1 In fact considerations 
 based on the work on thymus nucleic acid were the first that led to 
 formulating the structure of the complex nucleic acid as a polynucleotide, 
 of which the individual mononucleotides were composed of phosphoric 
 acid, sugar and base. Levene and Mandel have on hydrolysis of the 
 spleen nucleic acid with dilute sulphuric acid obtained a substance which 
 had the elementary composition (C U H 17 N 2 PO 10 ) of a complex consisting 
 of phosphoric acid, hexose and thy mine. On cleavage with 25 per cent, 
 sulphuric acid this body gave rise to phosphoric acid, levulinic acid and 
 thymine. This assumption is in harmony with subsequent discoveries 
 on the simple nucleic acid and on the yeast nulceic acid, and one feels justi- 
 fied in formulating the structure of thymonucleic acid in the following 
 manner : 
 
 OH H OH OH H 
 O CH 2 C C C C C- 
 
 O = P OH 
 
 H 
 
 H H 
 
 C 5 H 4 N S 
 
 -O 
 
 N 
 
 /~ OH H OH OH 
 
 = P O CH, C C C C C C 5 H 4 N 6 O 
 
 OH 
 
 H 
 
 H H 
 
 -O 
 
 Thus the details in the structure of the molecule of nucleic acids are 
 not yet known. But some general information is already obtained and 
 the route is singled out, by which the solution of the problem will be 
 reached. An indication is given for a point of departure for the work 
 on the synthesis of these substances. Work in that direction is now in 
 progress in our laboratory. 
 
 THE ROCKEFELLER INSTITUTE FOR MEDICAL RESEARCH, 
 NEW YORK CITY. 
 
THE FUNDAMENTAL LAW FOR A GENERAL THEORY OF 
 
 SOLUTIONS. 1 
 
 BY EDWARD W. WASHBURN. 
 Received March 3, 1910. 
 
 Nomenclature. 
 
 C Volume concentration. 
 
 (i) Cp, (2) Cp Molecular heat capacity of (i) a liquid, (2) a gas. 
 
 ACp Decrease in molecular heat capacity attending a change in 
 
 state of aggregation, 
 (i) KC, (2) KN Equilibrium constant in terms of (i) volume concentrations, 
 
 (2) mol fractions. (Products of the reaction in the denomi- 
 nator.) 
 
 KS Solubility product in terms of mol fractions, 
 
 (i) LS (2) Lg (3) Lp Molecular heat of (i) sublimation, (2) vaporization, (3) fusion 
 
 (under constant external pressure). 
 
 (i) N, (2) N' Mol fraction of (i) solvent, (2) solute, 
 
 (i) n, (2) n' Number of mols of (i) solvent, (2) solute. 
 
 p Gas or vapor pressure. 
 
 P External pressure on a liquid or solid. 
 
 Q x Heat evolved when the reaction aA + bB + .... = mM. + 
 
 N + . . . . takes place from left to right in a solution 
 
 under osmotic equilibrium. 
 R Gas constant. 
 
 (i) T, (2) Tp, (3) T , (i) Absolute temperature, (2) absolute temperature of the 
 (4) TB, (5) TB O freezing point of a solution, (3) of the freezing point of the 
 
 pure solvent, (4) of the boiling point of a solution, (5) of the 
 
 boiling point of the pure solvent. 
 U Total energy decrease produced when the reaction aA. + bE + 
 
 . . . . = mM. + nN + . . . takes place from left to right. 
 (i) v, (2) V Molecular volume of (i) a gas, (2) a liquid. 
 
 JT Osmotic pressure. 
 
 p. Thermodynamic potential. 
 
 tf> Fugacity. 
 
 6 Activity. 
 
 I. The Development of the Modern Theory of Solutions. 
 
 Upon the foundations laid by the labors of van't Hoff and Arrhenius 
 has arisen the structure which we know to-day as the Modern Theory of 
 Solutions. Before van't Hoff's epoch-making discovery of the ther- 
 
 1 Presented at the Second Decennial Celebration of Clark University, Worcester, 
 Mass., September 16, 1909. 
 
 52 
 
GENERAL, PHYSICAL AND INORGANIC. 654 
 
 modynamic relations which bind together the colligative properties 2 of 
 dilute solutions, our knowledge concerning these important quantities 
 was confined to a set of apparently unconnected empirical laws. Van't 
 Hoff's generalization of these laws, followed almost immediately by the 
 Ionic Theory of Arrhenius, stimulated greatly the study of solutions and 
 made possible the rapid development and perfection of our present theory. 
 Investigation has, however, been confined chiefly to the domain of dilute 
 solutions and the Modern Theory of Solutions has remained almost en- 
 tirely a theory of dilute solutions. The reason for this is, I believe, due 
 largely to one of those historical "accidents" which occur now and then 
 in the development of science. The history of this "accident" and the 
 manner in which it came about forms a chapter in physical chemistry of 
 interest alike to the chemist and to the philosopher. 
 
 Perhaps the best way to form a clear idea of the process of evolution 
 of our present theory of solutions is to consider first the colligative prop- 
 erties of solutions and the relations which connect them. These quan- 
 tities the osmotic pressure, vapor pressure, freezing point, boiling point, 
 etc. have played such an important and vital part in the development of 
 our solution theory that a clear idea of their relations to one another is 
 absolutely essential to a proper understanding of the theory and of its 
 development. The nature of these relations is expressed by the follow- 
 ing statement : The colligative properties of a solution are connected by a set of 
 rigorous differential equations which involve no assumptions except the two 
 laws of thermodynamics. The equations are as follows: 
 
 (1) Osmotic Pressure and Freezing Point, 
 
 dT F 
 V~ 
 
 (2) Vapor Pressure and Freezing Point, 
 
 / L F \ 
 
 = [ - (82) 
 
 \ V > - 
 
 (92) 
 (3) Osmotic Pressure and Vapor Pressure, 
 
 (77) 
 
 (4) Osmotic Pressure and Boiling Point, 
 
 'L. 
 
 (90) 
 
 To these should be added a number of others, such as the relation be- 
 tween the electromotive force of a concentration cell and either vapor 
 pressure (74) or osmotic pressure (70), and (16 and 14) the mutual re- 
 lations among the osmotic pressures or vapor pressures of the constituents 
 of a physical mixture or (30 and 300) the substances concerned in a 
 
 2 Following Ostwald, the term "colligative properties" is used to embrace such 
 properties as osmotic pressure, boiling point raising, freezing point lowering, vapor 
 pressure lowering, etc. 
 
 53 
 
655 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 
 
 chemical equilibrium, etc. 3 While the following discussion applies with 
 equal force to all of these relations, it will perhaps be conducive to clear- 
 ness, if we confine our attention chiefly to the four relations given above. 
 
 From the method of derivation of these relations, it is clear that they 
 do not involve any assumptions regarding the concentration of the solu- 
 tion, nor do they depend in any way upon the nature of the dissolved 
 solute or its degree of association, dissociation, or solvation. In fact, if 
 one knows, for example, the vapor pressure, freezing point lowering or 
 boiling point raising for a solution of any nonvolatile solute, he has the 
 means of calculating the osmotic pressure for the same temperature with- 
 out knowing either the concentration of the solution or the nature of the 
 solute. There may be one or several solutes present and they may as- 
 sociate, dissociate, or unite with each other or with the solvent in any 
 manner and to any extent. These questions are in no way involved in 
 the calculation. Since relations such as those existing among the collig- 
 ative properties of a solution involve only the two laws of thermody- 
 namics, it will be convenient to refer to them as "purely thermodynamic 
 relations" to distinguish them from an important group of relations which 
 involve the composition of the solution and the nature of its components, 
 and which we will now proceed to consider. 
 
 Let us consider a solution of any solute A in any solvent B, and let our 
 problem be to express each of the colligative properties of the solution 
 as a function of its composition or its "concentration." This problem 
 can in general be solved only by direct experiment for the particular 
 solvent and solute under consideration. From what has preceded, how- 
 ever, it is evident that as soon as we know the relation between any one 
 of the colligative properties and the composition of the solution, the other 
 relations become thereby determined. If, for example, we determined 
 the freezing point of the solution for a series of concentrations, we could 
 calculate thermodynamically the osmotic pressure, the vapor pressure, 
 etc., for the same concentrations and thus derive an equation connecting 
 each of these quantities with the concentration. The colligative property 
 which should be chosen for experimental study in a given case would 
 depend upon the relative ease and accuracy with which the several quan- 
 tities could be determined and the temperature range which it was desired 
 to cover; also in some cases upon whether the requisite "caloric quan- 
 tities" 4 were known with sufficient accuracy or could be determined readily. 
 
 The relation between any one of the colligative properties and the con- 
 centration of the solution for any given solvent and solute will obviously 
 depend upon the degree of association, dissociation and solvation of the 
 solute. 5 Since the magnitude of these effects and their dependence upon 
 
 3 The derivations of these relations and a more detailed discussion of them are 
 given in a previous paper, "A Simple System of Thermodynamic Chemistry Based 
 upon a Modification of the Method of Carnot" (Tins JOURNAL, 32, 467 (1910)). For 
 convenience in reference these equations are given the same number here as in the 
 previous paper where the significance of the quantities appearing in the equations is 
 explained in detail. 
 
 4 Proposed by van der Waals to distinguish heat capacities, latent heats, heats of 
 reaction, etc., from colligative properties. 
 
 5 It is hardly necessary to remark that this statement tacitly assumes that the 
 desired relation is to be one which involves the number of mols of the solute. 
 
 54 
 
GENERA!,, PHYSICAL AND INORGANIC. 656 
 
 the concentration are in general unknown quantities, the problem is too 
 complex for any complete solution. In general, therefore, it is necessary 
 to make a separate investigation for every solvent and solute in order to 
 establish the desired relation connecting some one of the colligative proper- 
 ties with the concentration. To leave the problem in this condition, how- 
 ever, is naturally not very satisfactory, and the course usually followed 
 by science when confronted with a problem which is too complex is first 
 to simplify the problem. Let us try to trace the process of simplification 
 which has been followed by science in the present instance. 
 
 Since association or dissociation of either solvent or solute molecules 
 introduces complications, the first step in the process of simplification is 
 obviously to consider the simple case of a solution in which neither takes 
 place. Since the union of a portion or all of the solute molecules with 
 the solvent molecules (solvation) is also a complicating factor, the next 
 step in the process of simplification would naturally be to eliminate this 
 factor also by assuming no solvation. After making these simplifications 
 our problem would read as follows: What are the relations connecting 
 the colligative properties with the composition in the case of a solution 
 in which the number of molecular species present is equal to the number 
 of components? Let us call such a solution, provisionally, an "ideal 
 solution," postponing until later a more definite and accurate description 
 of the properties of the type of solution to which the term "ideal" should 
 be applied. 
 
 There is, however, another method by which the complicating factor 
 of solvation can also be eliminated. Willard Gibbs, in his monumental 
 work on thermodynamic chemistry, has taught us that the proper way 
 to represent the composition of any phase is by the means of the mol 
 fractions of its several components. 7 
 
 Now in the case of a solution, the mol fraction of the solute (for ex- 
 ample) will be altered if it becomes solvated on going into solution, owing 
 to the consequent change in the number of solvent molecules. Such a 
 complication can be eliminated from our problem, as explained above, 
 by assuming no solvation; or it can be likewise eliminated by taking the 
 solution sufficiently dilute. For, as the solution becomes more and more 
 dilute, the limit approached by the mol fraction of the solute is the same 
 whether solvation occurs or not. 8 
 
 * For example, in the case of two components, a solvent and one solute, there 
 would be only two different kinds of molecules; for a solvent and two solutes, only 
 three different kinds of molecules, etc. 
 
 7 This system has been consistently followed by all investigators who use systems 
 of thermodynamics based upon Gibbs' thermodynamic potential. The reason that it 
 has not been followed by others is because they have confined themselves to the region 
 of dilute solutions, where it is possible to use one of the limiting forms approached by 
 the mol fraction of the solute, as the concentration approaches zero. 
 
 8 To illustrate, if we put n' mols of a solute in n mols of a solvent and no solvation 
 
 n' 
 
 (or dissociation or association) occurs, then the mol fraction of the solute is 
 
 (n' + n) 
 
 If, however, on the average x mols of solvent are combined with each mol of solute, 
 
 n' n' 
 
 the mol fraction of the (solvated) solute is or . As the 
 
 [n' + n n'x] \n'(ix) + n] 
 
 55 
 
657 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 
 
 Owing to an "historical accident" the latter method of eliminating the 
 complication of solvation has been the one followed by science, instead of 
 the former and more logical one. The "historical accident" 9 in this 
 instance was van't Hoff's brilliant discovery of the remarkably simple 
 equation connecting osmotic pressure with temperature and concentration 
 in very dilute solutions. Starting with this equation as a basis and using 
 the principles of thermodynamics, he showed us how to construct a com- 
 plete theory of dilute solutions. 
 
 As the field of dilute solutions became more and more developed, both 
 from the experimental and theoretical side, investigators began to turn 
 their attention to the subject of concentrated solutions. Investigation 
 in this direction has usually taken the direction of attempts to extend the 
 osmotic pressure equation by the introduction of quantities corresponding 
 to the a and b of van der Waals' condition equation for gases, upon the 
 basis of kinetic conceptions derived from an assumed analogy between 
 osmotic and gas pressure. Other investigators have sought to attribute 
 all of the deviation of concentrated solutions from the equations of dilute 
 solutions, to solvation, and have even gone so far as to compute on this 
 basis the approximate degree of hydration in some very concentrated 
 aqueous solutions, for example. Still other attempts have been taken in 
 the direction of an extension of our present equations by the addition of 
 a series of terms containing a number of constants intended to express 
 the influence of the solute molecules upon one another and upon the 
 solvent. 
 
 Attempts to obtain a satisfactory theory of concentrated solutions in 
 any of these directions give no promise of success. An attempt to "ex- 
 plain" why, as a solution becomes more and more concentrated, it de- 
 viates more and more from the equations of very dilute solutions is some- 
 what analogous to an attempt to explain why the sine of angle, which 
 for sufficiently small angles is equal to the angle, deviates more and more 
 as the angle grows larger. The reason is, of course, a purely mathematical 
 one. Similarly in the case of solutions there is first of all a purely mathe- 
 matical reason why concentrated solutions should deviate from the equa- 
 tions of the infinitely dilute solution. The equations of dilute solutions 
 are the limiting forms assumed by more general equations, owing to the 
 fact that certain terms become negligible as the concentration approaches 
 zero. In other words we have in our dilute solution laws only a portion, 
 the residue, so to speak, of a more general set of laws for solutions of all 
 
 solution becomes more and more dilute, both expressions approach - as their limit. 
 
 n 
 
 This is the familiar ratio which appears in our boiling point and freezing point equations. 
 
 (n'\ (RT\ 
 
 In the case of our osmotic pressure equation, instead of writing it jr== l~)\ ) 
 
 \n / \ r / 
 
 where V is the molecular volume of the solvent, it is customary to substitute V s = 
 nV and write nV s = n'RT. Here again, if the solution is sufficiently dilute, it is ob- 
 viously immaterial whether we understand V t to mean the volume of the solution or 
 the volume of pure solvent in which the n' mols of solute were dissolved in preparing 
 the solution. 
 
 * The expression, "historical accident," is, of course, used in the philosophical 
 sense. 
 
 56 
 
GENERAL, PHYSICAL AND INORGANIC. 658 
 
 concentrations. Consequently before science can hope to make any 
 progress in the region of concentrated solutions she must go back to the 
 point where the simplifying assumption of a dilute solution was uncon- 
 sciously introduced, and, in place of it, make the simplifying assumption 
 of an "ideal solution" as we have denned it above. We come, therefore, to 
 
 2. The Laws of the Ideal Solution. 
 
 Owing to the simplicity of the thermodynamic treatment of solutions 
 by what we may call the osmotic-cyclical-process method and the fact 
 that it uses conceptions which are comparatively easy to grasp and pro- 
 cesses which can be readily pictured in the mind, it has been the favorite 
 system among physical chemists. The fact that the theories developed 
 by the advocates of this method have been confined almost entirely to 
 the domain of the dilute solution is not due to any inherent fault in the 
 method. In addition to this method we have the systems of thermody- 
 namics based upon the Gibbs thermodynamic potential and its related 
 functions. These systems have been the favorite ones among physicists 
 and those who by training and inclination were accustomed to the use of 
 potential functions, and it is among the advocates of the thermodynamic 
 potential that we find the first successful attempt to formulate a theory 
 of solution which is free from the assumption that the solution must be 
 dilute. 
 
 This theory has been developed in Holland by van der Waals and his 
 associates, especially by van Laar. The first attempt was made in 1893 
 by Hondius Boldingh 10 in an Amsterdam Dissertation which so far as I 
 have been able to learn has never been published elsewhere. In the 
 following year van Laar 11 published two papers in which he derived a set of 
 "exact formulae for osmotic pressure, change in solubility, freezing point, 
 boiling point, etc." His results were expressed in a series of equations 
 in which the concentration of the solution appeared in a term, In(i-N'), 
 in which N' represents the mol fraction of the solute. The equations 
 contained, in addition, an undetermined function of the molecular ther- 
 modynamic potentials of the constituents. In numerous subsequent 
 publications van Laar has advocated with great warmth and zeal, the 
 use of the thermodynamic potential method and the introduction of the 
 concentration of the solution into the equations by means of the expression 
 ln(i-A 7/ ), instead of assuming that the solution is dilute. Van Laar has 
 in fact advocated a theory of solution which is entirely free from the 
 assumption that the solution must be dilute. The foundations for this 
 theory have existed in the literature for the last fifteen years. If it occurs 
 to any one to wonder why the theory has not come into general use in the 
 chemical world, he has only to glance through some of van Laar's papers, 
 especially his earlier ones, and the reason will be more or less obvious. 
 
 It is my present purpose to free this theory from the language of the 
 thermodynamic potential and to develop it in the so-called "osmotic 
 language." 12 Stated in this language, our problem is to determine the 
 
 10 Boldingh, "De Afwijkingen van de Wetten voor Verdunde Oplossingen." Dis- 
 sertation, Amsterdam, 1893. 
 
 11 van Laar, Z. physik. Chem., 15, 457 (1894). 
 
 12 The "language of the colligative properties" would be a better term. Too 
 much importance is usually ascribed to osmotic pressure in our solution theory. 
 
 57 
 
659 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 
 
 functional relation between some one of the colligative properties of the 
 solution and its concentration in the case of an ideal solution. Theoreti- 
 cally we can start with any one of the colligative properties we choose, but 
 since our present theory of dilute solutions is usually assumed to start 
 with the osmotic-pressure-concentration relation, it will perhaps be more 
 interesting to develop our theory of the ideal solution from the same 
 standpoint. 
 
 Let us, therefore, turn to the equation which expresses the osmotic 
 pressure 13 for a very dilute solution : 
 
 _ n'RT _ n'RT 
 ~T7 "~nV 
 
 In this equation, n' is the number of mols of solute in n mols of solvent 
 and V is the molecular volume of the pure liquid solvent. Let us now 
 make use of the method, introduced by Willard Gibbs, of expressing the 
 composition of the solution by means of the equation N' + N = i ,[ where 
 N' is the mol fraction of the solute and N that of the solvent. The 
 above equation can now be written : 
 
 RT 
 
 n' N'RT 
 
 n + n' 
 
 We have long recognized the fact that our osmotic pressure equation 
 expresses strictly only the limit approached by the osmotic pressure as 
 the concentration of the solution approaches zero. Let us therefore 
 write the equation itself so that it will indicate this fact. This gives us 
 
 (*N'\(RT\ 
 
 V1TAT/- 
 
 Seeing the equation in this form it is natural to suspect that the real 
 relation might possibly be 
 
 dN'\ fRT\ 
 
 AT AT/' (I 3) 
 
 or since by definition dN' = dN, 
 
 ft'p\ 
 
 -Jd\nN. (104) 
 
 Stated in words, this means that not only would the addition of dN' mols 
 of solute to a pure solvent involve an increase (i. e., from o to ATT) of 
 osmotic pressure which satisfies equation (104) but that it would also 
 involve the same increase in osmotic pressure when added to a solution 
 whose osmotic pressure is TT. If such proves to be the case (and we shall 
 see that in many cases, at least, it does) , our Modern Theory of Solutions 
 
 13 Throughout this paper, we shall understand by the term "osmotic pressure," 
 the pressure difference TT as defined by the equation TT = P P A , where P A is the 
 pressure upon the pure liquid solvent A when it is in equilibrium (through a membrane 
 or medium permeable only to itself) with the solution under the constant pressure P. 
 This has been discussed more fully in the previous paper (Tins JOURNAL, 32, 478 (1910)). 
 
 58 
 
GENERAL, PHYSICAL AND INORGANIC. 660 
 
 has remained a theory of infinitely dilute solutions, because we have 
 failed to recognize the fact that we have been working with true differen- 
 tial equations, and that in order to obtain the "theory of concentrated 
 solutions" which we have been seeking, the only thing we needed to do was 
 to integrate our equations. 
 
 In the case of osmotic pressure, for example, if we integrate equation 
 (104), we shall obtain an equation which contains no assumption whatever 
 regarding the concentration. The solution may be infinitely dilute or 
 infinitely concentrated or may have any concentration between these 
 limits. In order to do this we have only to put V = V (i + OTT), where 
 V is the molecular volume of the pure solvent under the standard pres- 
 sure P and a is its coefficient of compressibility, and on integration we 
 obtain the Boldingh-van Laar 1 * equation for osmotic pressure: 
 
 _ '!D f T t \ 
 
 Jln(i 
 
 * O * 
 
 (105) 
 
 Having come to the conclusion that the integral of equation (104) should 
 represent the osmotic pressure for an "ideal solution," whatever its con- 
 centration, we naturally seek for experimental confirmation before adopt- 
 ing it finally. 15 Owing to the great difficulty of making accurate and 
 
 14 The history of this equation (105) is very interesting. The differential form 
 as expressed by equation (104) was obtained by van der Waals as early as 1890 (Z. 
 physik. Chem., 5, 163) but no attempt was made to integrate it, only the case of dilute 
 solutions being discussed, for which case it assumes the form of equation (102) or 
 (100). In 1893 Hondius Boldingh, a student of van der Waals, making use of the 
 thermodynamic potential of Gibbs, derived equation (105) in the following form (Diss. 
 Amsterdam, 1893, p. 57): 
 
 xV = RT In (i N 1 ) + aN' 
 
 This differs from equation (105) as we have obtained it above, only in the fact that 
 the compressibility of the liquid is neglected and a small correction term aN' is added, 
 a being a quantity which, according to the molecular theory of van der Waals, expresses 
 the mutual influence of the components of the solution upon each other. For "ideal 
 solutions" it is negligible. 
 
 Boldingh apparently made no attempt to apply his equation. The same equation 
 was obtained the following year by van Laar (Loc. cit.) and in numerous publications 
 since then, this investigator has given various derivations of this equation usually by 
 methods involving the thermodynamic potential (cf., however, note 15). In 1897 
 an osmotic pressure equation in its essential points practically identical with equation 
 (105) was derived by Willard Gibbs (Nature, 60, 461 (1897)) by a method of balanced 
 columns. Finally G. N. Lewis, in a recent paper (Tins JOURNAL, 30, 675 (1908)), has 
 obtained equation (105) by a derivation involving his "activity" function and based 
 upon the assumption that the "activity" of the solvent is proportional to its mol 
 fraction. Both van Laar (Proc. Acad. Sci., Amsterdam, 9, 55 (1906)) and Lewis 
 (Loc. cit.) have discussed the relation of this equation to the van't Hoff equation and 
 have made comparisons of the values of osmotic pressure given by it with those obtained 
 by Morse and Fra/.er by direct measurement, in the case of aqueous solutions. 
 
 15 In view of the fact that the van't Hoff equation for osmotic pressure is usually 
 regarded as derivable from the kinetic theory by methods analogous to those used in 
 the kinetic derivation of the perfect gas laws (that is, on the assumption that osmotic 
 pressure is caused by the molecular bombardment of the solute molecules), it may 
 
 59 
 
66 1 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 
 
 reliable osmotic pressure measurements, it would be an unnecessary 
 waste of time and effort to seek experimental confirmation in this direc- 
 tion, especially as the equation can be tested just as satisfactorily by means 
 
 not be without interest to include here a brief kinetic derivation of the differential 
 form of equation (105). For this purpose I shall modify slightly the derivation given 
 by van Laar (Sechs Vortrage, p. 20). 
 
 Consider two solutions of the same solute in the same solvent, both under the ex- 
 ternal pressure P and separated from each other by a membrane permeable only to the 
 molecules of the solvent. According to a theorem of Boltzmann, the number of solvent 
 molecules which diffuse per second through a unit surface of the membrane in the 
 two directions is given by the expressions: 
 
 (a) From the weaker solution to the stronger, 
 
 UTB = (iN' w )eRT~ ( 107) 
 
 (6) From the stronger solution to the weaker, 
 
 i+PV f 
 
 n s = (/ N' f )e~Rf- ( 108) 
 
 In these equations e is the base of natural logarithms, N' w and N' s are the mol frac- 
 tions of solute in the weaker and the stronger solutions respectively, V is the volume 
 of the solution, R the gas constant, T the absolute temperature and A a quantity 
 which is a function of the temperature and which depends upon the units of measure- 
 ment. By adjusting the pressure on the two solutions we can make the number of 
 molecules of solvent which pass in the two directions equal ; in other words the two solu- 
 tions will be in equilibrium as respects the passage of the solvent from one to the 
 other. Under these conditions the right-hand members of the above equations can be 
 placed equal to each other, giving us the equation: 
 
 Or - 
 
 Let us now impose the condition that the "weaker solution" shall be the pure 
 solvent and that the "stronger solution" shall be an infinitely dilute solution in this 
 solvent and shall be under an external pressure P. Under these conditions the above 
 equation assumes the form 
 
 (i+PV) 
 Dividing through by e RT and using the logarithmic instead of the exponential 
 
 nomenclature, we obtain equation (104): 
 
 _ /?T\ 
 
 Jdln(z AT') (104) 
 
 After giving a kinetic derivation for equation (105), van Laar follows it with what 
 he terms a "rein thermodynamischer" proof. Such a proof is of course impossible, 
 if by "purely thermodynamic" we are to understand that the equation can be shown 
 to be a necessary consequence of the two laws of thermodynamics and nothing else. 
 In his papers on the subject, van Laar does not distinguish carefully between purely 
 thermodynamic relations and relations which involve additional assumptions. This 
 makes it difficult for the reader, who has not had considerable experience in the use of 
 the thermodynamic potential, to appreciate just what assumptions he is making and 
 what grounds he has for making them. Van Laar also falls into the error of attributing 
 the failure of the modern theory of solutions in the region of concentrated solutions, 
 to an inherent weakness in the osmotic method which he condemns severely, at the 
 same time advocating with great zeal the thermodynamic potential as the only quantity 
 
 60 
 
GENERAL, PHYSICAL AND INORGANIC. 662 
 
 of its thermodynamic derivatives. Of these we will consider first, the 
 vapor pressure derivative. The thermodynamic relation connecting 
 osmotic pressure and vapor pressure is 
 
 dr.= \^}*P' (77) 
 
 Combining this with equation (104) so as to eliminate it we obtain 
 
 Vdp = RTdlnN. (in) 
 
 RT 
 If the vapor can be regarded as a perfect gas we can put v = and 
 
 obtain 
 
 dln/> = dlnN (112) 
 
 which on integration gives 
 
 p = Pot* (3) 
 
 where p , the integration constant, is the vapor pressure of the pure 
 solvent. Since the terms solvent and solute are quite arbitrary, we can 
 state therefore in general that the partial vapor pressure of any constitu- 
 ent of an "ideal solution" is proportional to its mol fraction, if the vapor 
 obeys Boyle's law. We have therefore in equation (113) an excellent 
 means of testing our fundamental osmotic equation. 
 
 which is in a position to completely solve the problem (Sechs Vortrage, p. 19). 
 This point of view is absolutely unjustified and is doubtless partially responsible for 
 the fact that the many excellent and valuable features of this investigator's contribu- 
 tions to this problem have not received from the chemical world the consideration 
 which they deserve. Whether we should adopt a system of thermodynamic chemistry 
 based upon the entropy function (as worked out by Horstmann), or upon one of the 
 thermodynamic potentials of Gibbs or Planck, or upon the "fugacity" and "activity" 
 as defined by Lewis or upon the "osmotic pressure" and its related colligative properties, 
 is largely a philosophical question in which the personal equation is an important 
 factor. The "best" system from one point of view is not the "best" from another, 
 and instead of adopting one of these systems and severely condemning the others, we 
 should rather rejoice that the problems of our science are being attacked from these 
 different points of view. All of these systems rest upon the common ground of the 
 first and second laws of thermodynamics and any chemical problem which can be 
 solved in terms of one of them can be solved in terms of all. I cannot therefore agree 
 with van Laar, that the so-called "osmotic" system "lauft auf seinen letzen Beinen" 
 and "nach wenige Jahre wird abgereist sein." 
 
 Van Laar also attacks the so-called "gas theory" of solutions, that is, the theory 
 that what we call "osmotic pressure" is a real pressure which exists within an isolated 
 solution due to a molecular bombardment by the solute molecules. On this question, 
 I sympathize largely with van Laar's point of view. His exposition of the difficulties 
 in the way of such a theory is clear and convincing and I shall not, therefore, attempt 
 any further discussion of the question at this time. In this connection, however, it 
 is interesting to recall the views held by Willard Gibbs upon this point. In speaking 
 (Loc. cit.) of the osmotic pressure in the case of a solution A, containing a solute, D, 
 he says: 
 
 "But we must not suppose in any literal sense, that this difference of pressure 
 represents the part of the pressure in A which is exerted by the D-molecules, for that 
 would make the total pressure calculable by the law of Boyle and Charles." 
 
 6l 
 
663 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 
 
 The next question which confronts us is, where are we to look for 
 solutions whose characteristics approach most closely those which we 
 have assumed for our "ideal solution," or in other words where can we 
 find solutions for which we have reason to believe that we know the mol 
 fractions of the constituents in the solution? Our attention is naturally 
 directed towards mixtures of the so-called "normal" liquids of which 
 many examples are to be found among the hydrocarbons of the benzene 
 series and their substitution products. These liquids possess the property 
 of mixing with each other in all proportions, the process of solution being 
 accompanied by little if any heat effects or volume changes, such as 
 would, in general, necessarily occur, if the process of solution were ac- 
 companied by chemical reactions such as solvation or changes in the de- 
 gree of association or dissociation of any of the components. In general 
 the physical properties of these solutions are additive with respect to the 
 constituents. This behavior is, however, just what we should expect 
 in the case of the "ideal solution" which we have assumed. We may 
 therefore expect to find experimental confirmation of our osmotic pressure 
 equation in the case of these solutions. Fortunately data are at hand 
 in the vapor pressure measurements of Zawidski and others. These data 
 show most conclusively that equation (113) expresses the partial vapor 
 pressure for both constituents throughout the total concentration range 
 from zero to infinity for some dozen or fifteen different mixtures. 18 Freez- 
 ing point data furnish additional confirmation of the correctness of our 
 fundamental equation. Van Laar finds, for example, that the "freezing 
 point" curve for solutions of mercury in tin, throughout its entire range 
 (from t = 232 C., N' = o to i = 19, N f = 0.9964), is satisfactorily 
 represented by an equation which rests on the same basis as our funda- 
 mental osmotic pressure equation. 
 
 This perfect experimental confirmation, combined with the light which 
 is thrown upon the subject by the historical criticism, constitutes a most 
 convincing array of evidence in favor of the adoption of the Theory of the 
 Ideal Solution, as the best provisional General Theory of Solution. Before 
 turning to a more detailed consideration of the equations of the Ideal 
 Solution, let us state clearly the general characteristics of such a solution. 
 
 They are as follows : 
 
 18 The mixtures which obey this vapor pressure law are as follows: 
 (i) CO CH 8 C1; (2) C 6 H 14 C.H 18 ; (3) C 2 H 4 Cl 2 --C e H,; (3) C,H,Br, C.H.Br,; 
 (2) CH S OH C^OH; (2) CH 3 COOC Z H 6 C.H.COOC.H.; (2) C.H. C.H 6 CH 3 ; (4) 
 C.H 6 C 6 H 5 C1; ( 4 ) C.H.-C.H.Br; (2) C 8 H S CH 3 C 8 H 6 C V H 6 ; (4) C 6 H 6 CH S C.H.C1; 
 (4) CFsCHi- C 6 H s Br; (2) C 6 H S C1 C fl H s Br. 
 References: 
 
 1 Kuenen, Z. physik. Chem., u, 38 (1893). 
 1 Young, J. Chem. Soc., 81, 768; 83, 68 (1903). 
 
 3 von Zawidski, Z. physik. Chem., 35, 129 (1900). 
 
 4 Linebarger, THIS JOURNAL, 17, 615, 690 (1895). 
 
 This experimental confirmation of the theory of the ideal or "perfect" solution 
 was pointed out in a recent paper by G. N. Lewis (Loc. cit.) who has computed some 
 tables which exhibit in a very striking manner the excellent agreement of equation 
 (105) with the experimental data, even in the most concentrated solutions. 
 
 62 
 
GENERAL, PHYSICAL, AND INORGANIC. 664 
 
 I. The number of molecular species present is equal to the number of 
 components. 
 
 II. The physical properties of the solution are connected with the physi- 
 cal properties of its components in the pure state by the equation 
 
 X = xN + x'N' + x"N" + ... (114) 
 
 in which X is the molecular property in question (e. g., molecular heat 
 capacity, molecular volume, molecular refraction, molecular internal 
 energy, etc.), x (x', x", etc.) the molecular property of a constituent in 
 the pure state and N (N f , N", etc.) its mol fraction in the solution. 
 
 III. The third and most important characteristic is that which describes 
 the thermodynamic relations. The manner of stating this characteristic 
 depends upon what system of thermodynamics one chooses to make use 
 of. I shall therefore state it in three different "languages." 
 
 (a) The Gibbs Thermodynamic Potential System. According to van 
 Laar the thermodynamic characteristics of the "ideal solution" are ex- 
 pressed by the equation 
 
 ft = Ho + RTlnN (115) 
 
 in which /j. is the molecular thermodynamic potential of a constituent in 
 the solution, fio the molecular thermodynamic potential of the same 
 constituent in the pure state and N its mol fraction in the solution. 
 
 (6) The Fugacity- Activity System of Lewis. Lewis uses a system of 
 thermodynamic chemistry based upon two quantities, the "fugacity" 
 <j>, and the "activity" !;, whose relation to each other is expressed by the 
 equation 
 
 <!> = RT (116) 
 
 and which are connected with the thermodynamic potential by the equa- 
 tion 
 
 H = C + RTlntp (117) 
 
 where C is a function of the temperature only. According to Lewis 
 the "perfect solution" is defined by the equation 
 
 = SoN (118) 
 
 or what amounts to the same thing, 
 
 <p = (f> N. (119) 
 
 That van Laar's and Lewis' methods of describing the "ideal" or "perfect" 
 solution are identical is made evident by writing equation (i 19) in the form 
 
 RT\n<{> = RTlnfa + RTlnN, (120) 
 
 and combining it with equation (117) when we obtain at once equation 
 
 (US). 
 
 (c) The Colligati've Property System or the So-called Osmotic System. 
 According to this system, the relation between the colligative properties 
 of the Ideal Solution and its composition is expressed by a set of equations 
 which is composed of the equation 
 
 63 
 
665 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 
 
 (I04 ) 
 
 and its thermodynamic derivatives. 17 
 
 Having established fundamental equations for the Ideal Solution, let 
 us now derive a set of equations for such a solution similar to our present 
 equations for dilute solutions, but free from any assumptions as to the 
 concentration of the solution. In deriving such a set of equations we could 
 start either with our osmotic pressure equation (104) or the vapor pressure 
 derivative (112). In either case we should obtain the same set of equa- 
 tions. There is not much reason for choosing one of these equations 
 rather than the other as a starting point. Each possesses certain ad- 
 vantages for this purpose. In the following derivations, however, I shall 
 start with the osmotic pressure equation (104) in each case. This pro- 
 cedure will allow of direct comparison with our corresponding derivations 
 for dilute solutions and it moreover avoids the necessity of using the 
 gaseous phase in the derivation of a relation which is independent of the 
 properties of the vapor. The procedure for obtaining our set of equations 
 is very simple. In each instance, it consists simply in combining equation 
 (104) with the proper purely thermodynamic relation and then integrating 
 the result. The purely thermodynamic relations have all been obtained 
 by the author in the previous publication 3 to which the reader is referred 
 for their derivation. For convenience in reference these equations will 
 be designated by the same numbers as in the preceding publication. All 
 numbers below 100 refer to the previous paper. 
 
 3. Vapor Pressure. 
 
 We have already derived this equation for which the integrated form 
 is 
 
 P = P N (113) 
 
 where p is the partial vapor pressure of any molecular species from an 
 ideal solution in which its mol fraction is N, and p is its vapor pressure 
 in the pure liquid state at the same temperature. For a single non- 
 volatile solute whose mol fraction is N r this can also be written in the form 
 
 A* n' 
 
 r = N' = - -. (121) 
 
 Po (n + nO 
 
 If in a mixture of say two liquids, polymerization of one or both con- 
 stituents, or chemical combination between them occurs, we can obviously 
 make use of equation (113) to determine the exact nature and extent of 
 these processes if we know the necessary partial vapor pressure data. 
 Derivatives of equation (113) for special cases of association and of chemi- 
 cal combination have been applied recently with considerable success 
 
 17 Regarding the general characteristics of the Ideal Solution as stated above, it 
 should be noted that although in general the absence of heat effects or volume changes 
 on mixing two liquids may be taken as evidence for the absence of accompanying 
 chemical reactions, the reverse is not necessarily the case. Heat effects and volume 
 changes may and doubtless do occur in the absence of any chemical reaction, although 
 in such a case the heat effect will in the majority of cases be of quite a different order 
 of magnitude from that which is caused by a chemical reaction. 
 
 64 
 
GENERAL, PHYSICAL AND INORGANIC. 666 
 
 by Ikeda 18 and by Dolezalek 19 to the elucidation of the chemical condition 
 of several pure liquids and of their mixtures. The accumulation of 
 accurate and reliable vapor pressure data is of the highest importance to 
 a clearer and more complete knowledge of the nature of solutions. For 
 reasons which I have stated elsewhere, 21 the vapor pressure equation is 
 the relation best adapted to serve as a basis for the experimental attack 
 on the problem of concentrated solutions. 
 
 4. The Freezing Point Equation. 
 If we combine the purely thermodynamic equation 
 
 L F \ dT F 
 
 (82) 
 
 with our fundamental equation 
 
 _ RT 
 
 \ 
 
 Jdlntf (104) 
 
 so as to eliminate TT, we obtain the desired equation 2 
 
 For -very dilute solutions, we can of course substitute the freezing point 
 
 n' dN' 
 
 lowering A*/r in place of dT F and in place of ^ and obtain the 
 
 n jv 
 
 familiar law of Raoult-van't Hoff for freezing point lowering in dilute 
 solution : 
 
 It is preferable, however, to integrate our differential equation and 
 thus obtain a general equation for an ideal solution of any concentration. 
 Before doing this we will substitute in equation (122) 
 
 T Atp = T F , i N' = N and <*( A*/r) = dT F 
 
 where A//r is the freezing point lowering in centigrade degrees and T 
 is the freezing point of the pure solvent on the absolute scale. This gives 
 us 
 
 dN' L F (i N') 
 
 In order to integrate, we must first express L F as a function of At F which 
 is done by the following purely thermodynamic equation: 
 
 L F = L Fo ACp A< F y,a(A*F) f V^A^)' .... (85) 
 
 18 Ikeda, J. Coll. Sri. Imp. Univ. Tokyo, 25, Art. 10 (1908). 
 
 19 Dolezalek, Z. physik. Chem., 64, 730 (1908) ; see also Moller, Ibid., 69, 449 (1909). 
 zo This equation was obtained by Boldingh (Loc. tit., p. 61) in the following form: 
 
 where a has the meaning explained in note (14). Boldingh integrated his equation 
 under the assumption that L F is independent of T. 
 
 65 
 
667 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 
 
 In this equation Lp is the molecular heat of fusion of the pure solvent 
 at its freezing point T , ACp is the attendant decrease in the heat capacity 
 of the system and a, /?, etc., are constants expressing the dependence of 
 ACp upon the temperature. Combining (85) with (125) we obtain finally 
 (neglecting /?) : 
 
 dN' [L Fo &Cpo l /,a(W](i N') 
 
 This equation can now be integrated. A convenient way to do this 
 is to integrate into a power series in the desired variable by applying 
 McL/aurin's theorem directly to the differential equation, carrying the 
 series only so far as the accuracy of the experimental data warrant for 
 the particular case under consideration. For example, in the case of 
 water solutions if A/ F be known to 0.001, then for values of Atp which 
 do not exceed 7, the terms containing a, (3, etc., are negligible and 
 the application of McL/aurin's theorem gives us the equations 21 
 
 Fo F A t 
 
 v L F ~ 
 
 AT* ro I A j i / I "Til . r" I / A \ I / \ 
 
 N' atp l /,{ H I ( A^ F ) a (127) 
 
 >-T o I / I r-fc*nn A * r T^ / \ * ' 
 
 and 
 
 the remaining terms in the expansion not being significant. 
 
 If we desire to follow a freezing point curve through a considerable 
 range of temperature, the general integral of equation (126) is more ad- 
 vantageous. The general integral is 
 
 * o 
 (AC Po + aT ) Afr + V 2 a Afr] L Fo 
 
 Equations of this general character have been derived by several ob- 
 servers 22 and the corresponding theoretical curves have been compared 
 with the experimental curves for a number of systems with good agreement. 
 In these comparisons, however, the constants of the theoretical equation 
 have been evaluated from the freezing point data themselves, so that 
 the agreement loses a good deal of its significance. 
 
 5. The Boiling Point Equation. 
 By combining the purely thermodynamic equation 
 
 21 The application of equation (127) to the data for aqueous solutions and the 
 interpretation of the results obtained have been discussed by the author in a previous 
 paper (Technology Quarterly, 21, 370 (1908)). This application was made on the 
 assumption that the molecular weight of liquid water is 18. Although the results ob- 
 tained on this assumption were fairly satisfactory up to a concentration of i molal, it 
 is clear that a complete study of the behavior of aqueous solutions from the stand- 
 point of the laws of the Ideal Solution must take into account the degree of associa- 
 tion of the solvent. Further investigations along this line are now in progress in 
 this laboratory. 
 
 22 e. g., van Laar (Versl. K. Akad. van Wet., Amsterdam, 1903 and 1904; several 
 papers) Roozeboom ('Die Heterogene Gleichgewicht," 2, 267 et. seq.), and Yamamota 
 (/. Cott. Sci. Imp. Univ. Tokyo, 25, Art. n (1908)). 
 
 66 
 
GENERAL,, PHYSICAL, AND INORGANIC. 668 
 
 with equation (104) so as to eliminate TT we obtain the desired equation 
 
 ' 
 
 (I30) 
 
 which for very dilute solutions takes the familiar form 
 
 In order to integrate the differential equation (130) we have only to ex- 
 press LT, as a function of the temperature. The First Law of Thermo- 
 dynamics gives us the rigorous equation 
 
 dL, L v /^W^\ 
 
 &-*-**+-(-;)(&), 
 
 by means of which we can calculate the temperature coefficient of L,. 
 If the vapor behaves as a perfect gas this equation becomes 
 
 ^ = ACp (133) 
 
 dl 
 
 and the methods of integration of equation (130) become perfectly analo- 
 gous in every respect to those followed in the case of the freezing point 
 equation in the preceding section. It is not necessary therefore to discuss 
 them in detail. The final equations have the same form as the corre- 
 sponding ones for the freezing point lowering. 
 
 6. Chemical Equilibrium. 
 
 Two examples will be sufficient to illustrate the method of derivation 
 of the laws which regulate chemical equilibrium in the ideal solution. 
 Let the equilibrium be expressed by the equation : 
 
 oA + 6B + ..... ^~ > mM + N + ... (134) 
 
 (a) The Effect of Concentration. The purely thermodynamic equation 
 for the effect of concentration upon chemical equilibrium in a liquid phase 
 at constant temperature and pressure is 
 
 aVfidittL bVzdxB ..... + mVud^M + nV^dify + ... == o . (300) 
 According to equation (104) the osmotic pressure for each substance 
 taking part in the equilibrium is 
 
 Fxcfcrx = RTdlnN*. (135) 
 
 Combining these two equations we obtain the relation 
 
 j #!' 
 
 -~=*" (136) 
 
 where K v is a constant. This expression differs from the Guldberg- 
 Waage Law only in the substitution of the mol fraction N, in place of 
 the volume concentration C. Equation (136) was obtained by Planck 23 as 
 early as 1887, and the reasons for adopting it in place of the Guldberg- 
 Waage form and for expressing the composition of solutions in terms 
 of mol fractions instead of mols per liter were clearly stated by him at the 
 same time. 
 
 (6) The Effect of Temperature. The purely thermodynamic relation is 
 
 OxdT 
 . . . + ml/ M rf~ M + nV^dr^ + . . . = . (380) 
 
 Planck, Wied. Ann., 32, 489 (1887). 
 
 6? 
 
669 FUNDAMENTAL LAW FOR THEORY OF SOLUTIONS. 
 
 Combining this with equations (136) and (135) and introducing the First 
 Law of Thermodynamics we obtain the equation 
 
 d^Kff = U_ 
 dT RT* 
 
 which is identical with the van't Hoff Law, with the substitution of Kjy 
 in place of the Guldberg-Waage constant KC- In general it may be 
 stated that the laws for chemical equilibrium in an ideal solution may 
 be obtained from our present dilute solution laws by substituting mol 
 fractions in place of volume concentrations. This applies also to hetero- 
 geneous equilibrium. The Solubility Product Law, for example, for a 
 saturated solution of the solute BC which dissociates into B and C be- 
 comes 24 
 
 WB'NC = const. = KS. (138) 
 
 7. Concluding Discussion. 
 
 Lest any one from the perusal of the foregoing pages should gain the 
 impression that the problem of a satisfactory general theory of solutions 
 may be regarded as completely solved, it will be well to examine for a 
 moment, in a general way, the characteristics of the Theory of the Ideal 
 Solution with respect to its advantages and disadvantages when regarded 
 as the basis for a general theory of solutions. When compared with the 
 Theory of Dilute Solutions we must acknowledge that it constitutes a 
 distinct and decided step forward. One requirement of a satisfactory 
 general theory of solutions is that it shall represent the facts throughout 
 the whole range of concentrations for some type of solution, at least. 
 This requirement is fulfilled by the Theory of the Ideal Solution and we 
 may feel considerable certainty that any deviation from the requirements 
 of this theory, in a given case, is due to physical or chemical causes and 
 capable of a physical or chemical explanation and is not simply the result 
 of attempting to apply a set of incomplete laws which do not and could 
 not be expected to hold for any kind of a concentrated solution no matter 
 how simple its character. 
 
 The success of the Theory of the Ideal Solution as an instrument for 
 throwing light upon the processes occurring in solutions has already been 
 demonstrated in several instances. In the case of several solutions which 
 apparently exhibit a behavior contrary to the requirements of the Theory, 
 Dolezalek 19 has shown that perfect agreement between theory and ex- 
 periment exist if the assumption be made that a simple compound is 
 formed between the two constituents or that one of them is partially 
 associated. In the case of acetone and chloroform for example, the as- 
 sumption of a single compound, CHC1 3 (CH 3 ) 2 CO, and the introduction 
 of the corresponding equilibrium constant into the equations sufficed to 
 produce complete agreement between theory and experiment. It is true 
 that the value of the constant was computed from the vapor pressure 
 data themselves, but in a recent paper 19 Holier has shown that the values 
 of such constants may be obtained independently of the vapor pressure 
 data of the solution under consideration and that they therefore possess 
 24 This is obtained by combining equations (51) and (104). It does not involve 
 the Mass Action Law [i. e., equation (136)], which is usually assumed as the basis for 
 the derivation of the Solubility Product Law. This point, which was brought out in 
 the previous paper, has been overlooked in all of the textbooks of physical chemistry, 
 although it was explained clearly by Planck as early as 1887 (Loc. cit.). 
 
 68 
 
GENERAL, PHYSICAL AND INORGANIC. 670 
 
 the physical significance ascribed to them and are not simply empirical 
 constants of an interpolation formula. 
 
 In all the cases studied by Dolezalek he found that agreement between 
 experiment and theory is produced if the assumption be made that what 
 appears to be a deviation from the theory is simply due to the fact that 
 the numbers assumed as the mol fractions of the two constituents 
 in the solution are incorrect and that when the proper mol frac- 
 tions are used, the apparent discrepancy disappears. If we were 
 justified in assuming that all solutions are really ideal solutions and 
 that what appear to be exceptions are merely due to our inadequate 
 knowledge of the number and kind of the various molecular species present 
 and their respective mol fractions, then the Theory of the Ideal Solution 
 would constitute a general theory including all solutions and all con- 
 centrations and would enable us to ascertain just what occurs chemically, 
 when the solution is formed out of its constituents. Unfortunately such 
 is not the case, for it can be easily shown mathematically that if certain 
 liquids form an ideal solution with one another they must be miscible 
 in all proportions. The solutions in a system composed of two or more 
 liquid phases in equilibrium with one another cannot therefore be governed 
 to the laws of the Ideal Solution. Moreover, these exceptions are not 
 merely apparent but are real and cannot be explained on the grounds of 
 association, dissociation or chemical combination. The explanation 
 must be looked for in a radical difference in the physical nature of the 
 medium. 
 
 To illustrate by an extreme case, let us consider a system composed of 
 a solution of benzene in mercury and a solution of mercury in benzene, 
 both solutions in equilibrium with each other. The vapor pressure of 
 benzene from the mercury layer is equal to its vapor pressure from the 
 benzene layer and yet the mol fraction of benzene in the mercury layer 
 is probably so small that we could not detect it by any analytical means, 
 while in the benzene layer it is equal to i , within the limits of our ability to 
 measure it. The equality of the vapor pressure from the two layers can 
 only be due, therefore, to the fact that the nature of the medium between 
 the molecules of mercury is such that the benzene molecules can penetrate 
 it only with the greatest difficulty. This effect of the physical nature of 
 the medium is therefore one which must be taken account of in all applica- 
 tions of the Theory of the Ideal Solution. In order that the laws of the 
 Ideal Solution shall apply, the nature of the medium or the field of force 
 in which the molecules find themselves in the solution must not be -very 
 different from that of the pure liquid itself. Although this restricts some- 
 what the sphere of usefulness of the theory, there still remain a large 
 number of cases where it should prove of the greatest value in the elucida- 
 tion of the chemical nature of solutions. Even in cases where the theory 
 cannot be extended over all concentrations because of a consequent 
 radical change in the physical nature of the medium, we may still hope 
 to obtain valuable results with its aid in solutions of moderate concen- 
 trations. At all events, I believe that the Theory of the Ideal Solution 
 is the one which should be adopted as the basis for reference, classification 
 an interpretation of the experimental data on solutions in place of our 
 present Theory of the Infinitely Dilute Solution which is only a special, 
 though very important, case of the former theory. 
 
 URBANA, ILLINOIS, Feb. i, 1910. 
 
 6 9 
 
A REVIEW OF SOME RECENT INVESTIGATIONS IN THE QUIN- 
 
 AZOLINE GROUP. 1 
 
 BY MARSTON TAYLOR BOGERT. 
 Received March 31, 1910. 
 
 For several years past, the Organic Laboratory of Columbia Univer- 
 sity has been engaged in the synthesis and study of compounds belonging 
 to that group of organic heterocycles known as quinazolines or phen- 
 miazines. 
 
 To us, the work has been most interesting and enjoyable. The com- 
 pounds obtained have been generally crystalline solids, quite readily 
 purified, stable, and very satisfactory to work with. 
 
 Our investigations have included A. Quinazolines, B. Thioquinazo- 
 lines, and C. Naphthotetrazines of quinazoline structure : 
 
 N N N 
 
 N - NN 
 
 (Quinazoline) (Thioquinazoline) (1,3,7,9-Naphthotetrazine) 
 
 Incidentally, a great many new preparatory, intermediate and sub- 
 sidiary products have been obtained. From the standpoint of new sub- 
 stances, the field has been an unusually fruitful one. 
 
 It is, therefore, not only an honor but also a pleasure to present on 
 this occasion a brief synopsis of the major lines of the work to date. 
 
 A. Quinazolines. 
 
 Colby and Dodge, 2 as the result of their investigations of the inter- 
 action of nitriles and organic acids, under conditions of heat and pres- 
 sure, came to the following conclusions: 
 
 I. Fatty nitriles and aromatic acids give fatty acids and aromatic 
 nitriles. 
 
 II. Aromatic nitriles and fatty acids give mixed secondary amides. 
 
 III. Aromatic nitriles and aromatic acids give secondary amides, un- 
 less the temperature is very high, when the nitrile of the higher radical 
 may form. 
 
 Mathews, 3 in continuation of this work, heated acetonitrile and an- 
 thranilic acid together under pressure, hoping thereby to obtain the 
 
 1 Presented at the Twentieth Anniversary Celebration of Clark University, Wor- 
 cester, Mass., Sept. 14, 1909. 
 
 2 Am. Chem. J ., 13, i (1891). 
 
 3 THIS JOURNAL, 20, 654 (1898). 
 
 70 
 
RECENT INVESTIGATIONS IN THE QUINAZOLINE GROUP. 785 
 
 anthranilic nitrile. On examining the contents of the tube, he found 
 not the nitrile desired but a colorless crystalline compound, melting 
 at 232 (uncor.), which was not identified at the time. 
 
 Later, Bogert and Gotthelf 1 made a more careful study of this reac- 
 tion and found that the crystalline substance melting at 232 was identical 
 with the 2-methyl-4-ketodihydroquinazoline first described by Weddige, 2 
 and later obtained by Bischler and Burkart, 3 Bischler and Lang, 4 and 
 Niementovskii. 5 By varying the nitrile, they obtained other quinazolines 
 of analogous structure. 
 
 Continuing this work, Gotthelf 8 heated anthranilic acid under pressure 
 with a: 
 
 IV. Fatty nitrile alone (using aceto-, propio-, w-butyro-, t-valero- and 
 i-capronitriles). 
 
 V. Fatty nitrile and the corresponding fatty acid (acetonitrile and 
 acetic acid, propionitrile and propionic acid, etc.). 
 
 VI. Fatty nitrile and a higher fatty acid (acetonitrile and propionic 
 acid, n-butyronitrile and capric acid, etc.). 
 
 VII. Fatty nitrile and a lower fatty acid (isocapronitrile and pro- 
 pionic acid, etc.). 
 
 VIII. Fatty nitrile and the corresponding acid anhydride (propioni- 
 trile and propionic anhydride, valeronitrile and valeric anhydride, etc.). 
 
 IX. Fatty nitrile and higher acid anhydride (acetonitrile and pro- 
 pionic anhydride, etc.). 
 
 X. Fatty nitrile and lower acid anhydride (acetonitrile and formic 
 acid, etc.). 
 
 In considering case IV, Bogert and Gotthelf at the time thought it 
 probable that the production of a quinazoline was due to the formation 
 of an intermediate secondary amide. 
 
 ,NH, X X = 3 
 
 C.H 4 < + CH 8 CN = C.A 4 < fi 1 =C 6 H 4 < | + H,O 
 
 VOOH X CONHCCH 3 X CO . NH 
 
 just as acetonitrile and acetic acid when heated under pressure give 
 diacetoamide. 7 
 
 One objection to this explanation of the course of the reaction lies 
 in the fact that it involves a lactam condensation, whereas Weddige's 
 investigations in this very field have made it quite clear that these con- 
 densations follow preferably the lactim course. If the intermediate 
 secondary amide assumed by us passes directly into the quinazoline by 
 loss of water, two different quinazolines should result according to whether 
 the condensation is of lactam or lactim type : 
 
 y 
 
 C 6 H 4 < 
 N 
 
 O 
 
 +H t O 
 
 CONHCCH, CO . NH 
 
 (a) 
 
 1 THIS JOURNAL, 22, 129 (1900). 
 
 2 J. prakt. Chem., [2] 31, 124 (1885). 
 
 3 Ber., 26, 1350 (1893). 
 
 4 Ibid., 28, 282 (1895). 
 
 8 /. prakt. Chem., [2] 51, 564 (1895) and Ber., 29, 1360 (1896). 
 
 THIS JOURNAL,., 23, 6n (1901). 
 
 7 Kekuld, Lehrbuch (ist ed.), i, 574; Gautier, Ztschr. Chem., 1869, 127. 
 
 71 
 
786 ORGANIC AND BIOLOGICAL. 
 
 6 H 4 <( 
 
 NH H OH .NH.CCH, 
 
 + H,0 
 
 CON:CCH 3 CO.N 
 
 (*) 
 As a matter of fact, the product obtained by us is identical with (a). 
 
 Another objection is that it is not in harmony with the conclusions 
 of Colby and Dodge 1 cited above. According to their experiments, 
 the first products of the action of a fatty nitrile upon an aromatic acid 
 at high temperature and pressure are the aromatic nitrile and the fatty 
 acid, which may and often do subsequently combine to a mixed secondary 
 amide. That the secondary amide is not the first product seems established 
 by their results, for in no case where a fatty nitrile acted upon an aro- 
 matic acid was the secondary amide found unaccompanied by aromatic 
 nitrile, while in many cases aromatic nitrile and fatty acids were found 
 unaccompanied by any secondary amide. Thus, acetonitrile and benzoic 
 acid at 220 gave no acetobenzamide, but only benzonitrile and acetic 
 acid, whereas when the latter two were heated together at 220, only 
 acetobenzamide was formed. 
 
 It therefore seems probable that the first phase of the reaction be- 
 tween anthranilic acid and a fatty nitrile is as follows: 
 HH, /NH, 
 
 + RCN = c e H K + R.COOH 
 
 COOH \CN 
 
 As aniline when heated to sufficiently high temperatures with fatty 
 acids yields the corresponding anilides, 2 the second phase of the reaction 
 is probably 
 
 .NH, .NH.COR 
 
 C 6 H 4 < + R.COOH = C 9 H 4 < + H,0. 
 
 / 
 4V 
 
 \ 
 
 As the ease with which this acylation takes place decreases with in- 
 crease in the molecular weight of the fatty acid, the higher nitriles should 
 give smaller yields of the quinazoline, and this was found to be the case. 
 The yield with propionitrile, for example, was 22.5 per cent., while with 
 valeronitrile it was only 5 per cent, of the theoretical. 
 
 The acylanthranilic nitrile may then pass into the quinazoline by either 
 of the following reactions: 
 
 .NH.COR xNH.COR ,K = CR 
 
 C 6 H 4 < + H 8 0=C 6 H,< = C 6 H 4 < I +H k O 
 
 X CN \CONH, \CO . NH 
 
 or 
 
 xNH.COR X NH.COR /N = CR 
 
 C 6 H 4 < + R.COOH = C 6 H 4 < =C 6 H 4 < | + R.COOH. 
 
 \CN \CONHCOR X CO . NH 
 
 That a simple molecular rearrangement of the acylanthranilic nitrile 
 occurs, 
 
 xNH.COR N = CR 
 
 CN co . NH 
 
 seems unlikely, for the reason that when acetoanthranilic nitrile was 
 heated for some time above its melting point, or when its solution in 
 dry toluene was heated to high temperatures in sealed tubes, no change 
 
 1 Loc. cit. 
 
 2 Williams, Ann., 131, 288; Pebal, Ibid., 91, 152. 
 
 72 
 
. 
 
 RECENT INVESTIGATIONS IN THE QUINAZOUNE GROUP. 787 
 
 whatever occurred. 1 Moisture was, of course, rigidly excluded in these 
 experiments, since a small amount of water, by successive addition and 
 splitting off, would suffice to convert an indefinite amount of the nitrile 
 to the quinazoline. 
 
 In further support of the assumption that the acylanthranilic nitrile 
 is an intermediate product, are the following facts: (i) Acetanilide is 
 found as a by-product in the tubes. 2 (2) The presence of a small amount 
 of acetic anhydride greatly increases the yield of quinazoline. (3) The 
 same quinazoline results when acetoanthranilic acid is heated in a sealed 
 tube with acetonitrile as when anthranilic acid itself is used. 3 (4) Aceto- 
 anthranilic nitrile on partial hydrolysis changes immediately to the 
 quinazoline. 4 
 
 The by-products observed in the experiments were carbon dioxide, 
 aniline, anilides, amides and ammonia. Of these, carbon dioxide and ani- 
 line are normal decomposition products of anthranilic acid at high tem- 
 peratures. Partial hydrolysis of the nitrile accounts for the presence of 
 amide. Aniline acting on the latter, 5 or upon the fatty acid present, 
 yields the anilide, the by-product in the former case being ammonia. 
 
 In those cases (V, VI and VII) where the anthranilic acid was heated 
 with both the fatty nitrile and the fatty acid, the results are confusing 
 and the interpretation obscure. Quinazolines were formed, but the 
 course of the reactions is not clear and additional work is needed before 
 any satisfactory conclusions can be reached. 
 
 When an acid anhydride was added to the tubes containing the an- 
 thranilic acid and fatty nitrile (VIII, IX and X), the anhydride used 
 determined the quinazoline formed in practically every case. In these 
 experiments, the reaction is therefore probably as follows: 
 
 y NH, .NH.COR 
 
 C 6 H,< + O(CO.R) 2 = C 6 H 4 < + R.COOH 
 
 X COOH X COOH 
 
 /NH.COR /NH.COR 
 
 C 6 H/ + R'CN = C 6 H/ 
 
 X COOH X CONHCOR', 
 
 the latter then~condensing in either of the following ways: 
 
 N:C 
 
 X ,N 
 
 CONH 
 
 OH 
 COR 
 
 ).NH 
 
 + R'COOH (a) 
 
 C 6 H/ 
 
 N HCOR 
 
 ,N = CR' 
 
 R' 
 
 = C 8 H 4 / | + R.COOH 
 
 VO . NH 
 
 The nitrile was used with the corresponding acid anhydride (VIII), 
 with a higher acid anhydride (IX), and with a lower anhydride (X). Of 
 these, types VIII and IX invariably yielded pure quinazolines according 
 to reaction (a) above. Only when a lower anhydride was used with the 
 
 1 Bogert and Hand, THIS JOURNAL, 24, 1034 (1902). 
 
 2 Bogert and Gotthelf, Ibid., 22, 528 (1900). 
 
 3 Bogert and Gotthelf, Loc. cit. 
 
 4 Bogert and Hand, Loc. cit. 
 
 6 Kelbe, Ber., 16, 1200 (1883). 
 
 73 
 
788 ORGANIC AND BIOLOGICAL. 
 
 nitrile (X), were products encountered which were mixtures of quinazo- 
 lines. 
 
 Of these different sealed-tube reactions, much the best was that in 
 which the anthranilic acid was heated with the fatty nitrile and the 
 corresponding acid anhydride (VIII). The yield by this process was 
 fair (30 to 50 per cent, of the theory) and, unless the heating was too 
 high, the tube contents were invariably light-colored and crystalline. 
 
 In the foregoing, it is assumed that the secondary amide is an inter- 
 mediate product in the formation of the quinazoline. Such an amide, 
 R.CO.NH.CO.R', being symmetrical, should be producible either from 
 R.COOH and R'CN, or from R'COOH and RCN. In other words, 
 since the formation of the CO.NH.CO group is due solely to the 
 combination of the CN and COOH, it should make no difference which 
 radical carries the CN and which the COOH. The same secondary amide 
 and, therefore, the same quinazoline, should result whether the acylan- 
 thranilic acid is heated with the fatty nitrile, or the acylanthranilic nitrile 
 with the fatty acid (or its anhydride). On testing this practically, 1 such 
 was indeed found to be the case, and a number of quinazolines were 
 thus obtained from the acylanthranilic nitriles by heating them in sealed 
 tubes with the fatty acid or, better, its anhydride. 
 
 In experimenting with these acylanthranilic nitriles, a method of 
 converting them into the quinazolines, far superior to any of the methods 
 described above, was discovered. It consists in digesting the acylan- 
 thranilic nitrile for a few minutes with a warm alkaline dioxide solution, 
 and is really a beautiful method, being very rapid, simplicity itself in 
 execution, and giving large yields of practically pure quinazolines. It 
 depends upon the hydrolysis of the nitrile to the amide, the acylanthranil- 
 amide then condensing to the quinazoline, as shown by Weddige. 2 
 
 In those cases where the o-amino acid is best obtained from its nitrile 
 by saponification, it is convenient to be able to pass direct from the 
 nitrile to the quinazoline. Thus, homoanthranilic nitrile is readily 
 prepared from ra-nitro-/>-toluidine, through w-nitro-/>-toluonitrile, and 
 from the acyl derivatives of this homoanthranilic nitrile and an alkaline 
 dioxide solution (hydrogen dioxide solution made alkaline with sodium 
 hydroxide), the 7-methyl-4-quinazolones were prepared. 3 
 
 By a number of different processes, including those already mentioned, 
 starting with brominated anthranilic acdis, bromoquinazolines were pre- 
 pared. 4 
 
 Our attention was next turned to the nitroquinazolines, and many 
 were made from nitroanthranilic acids by the methods already described, 
 and also by heating the ammonium salt of the nitroanthranilic acid 
 with formamide, 5 by the direct action of heat on the ammonium salts 
 of nitroacylanthranilic acids, 6 and by the action of primary amines on 
 nitroacetoanthranils. 7 The last is a very fine method indeed, and one 
 we have developed quite extensively. 
 
 1 Bogert and Hand, THIS JOURNAL, 24, 1031 (1902). 
 
 2 J. prakt. Chem., [2] 31, 124 (1885); 36, 141 (1887). 
 
 3 Bogert and Hoffman, THIS JOURNAL, 27, 1293 (1905). 
 
 4 Bogert and Hand, Ibid., 25, 943 (1903); 28, 94 (1906). 
 
 5 Niementovskii, /. prakt. Chem., [2] 51, 564 (1895). 
 8 Bischler and Burkart, Ber., 26, 1349 (1893). 
 
 7 Anschiitz, Schmidt and Griffenberg, Ber., 35, 3480 (1902). 
 
 74 
 
RECENT INVESTIGATIONS IN THE QUINAZOLINE GROUP. 789 
 
 By these various methods, we prepared 5-nitro-, 1 6-nitro- 2 , and y-nitro- 
 4-quinazolones. 3 Of the four possible types of benzoylnitroquinazolines, 
 representatives of the 6-nitro, 4 and 8-nitro, 5 were already known. The 
 preparation of the 5-and y-nitro derivatives completed the series. 
 
 Reduction of the nitroquinazolines yielded the corresponding benzoyl- 
 aminoquinazolines, 6 in which, as might have been expected, the amino 
 group shows the usual aniline reactions. 
 
 Aminoquinazolines with the amino group on the miazine side of the 
 nucleus were produced by condensing simple or substituted acylanthranils 
 with primary hydrazines, 7 
 
 N.COR /N = CR 
 
 H,N.NHR' = C 6 H 4 < | + H S O. 
 
 \CO . N.NHR' 
 
 With hydrazine itself, it was also found possible to condense two mol- 
 ecules of the anthranil with one of the hydrazine, thereby giving 3,3'- 
 diquinazolonyls, 
 
 = Cr RC = N, 
 
 . N N. CC 
 
 The same result can be accomplished, though less satisfactorily, by con- 
 densing the 3-aminoquinazoline with a second molecule of the anthranil. 
 The di-quinazolonyls so far isolated are all very difficultly soluble and 
 inert. 
 
 The 3-aminoquinazolines proved interesting because of their unsym- 
 metrical secondary hydrazine structure, >N.NH 2 . In the main, their 
 properties coincide with those of other N-amino heterocyclic compounds. 
 Thus, nitrous acid does not diazotize the amino group, but replaces it 
 by hydrogen; with diacetosuccinic esters, they often yield pyrrole de- 
 rivatives; 8 with aromatic nitroso bodies, they do not give azo compounds; 
 nor are they oxidized to tetrazones by mercuric oxide. On the other 
 hand, they do not usually condense with ketones, while they do occasion- 
 ally yield phenyluramino derivatives with phenyl isocyanate. 9 In the 
 elimination of the N-amino group by the action of nitrous acid, there 
 must be some unstable intermediate product formed, for if immediately 
 after the addition of the nitrous acid the mixture be poured into an alkaline 
 solution of alpha- or beta-naphthol, dyestuffs are formed of considerable 
 tinctorial power, the structure of which has not been elucidated. 
 
 Further experimentation with the acylanthranils showed that they 
 
 1 Bogert and Chambers, THIS JOURNAL, 27, 649 (1905); Bogert and Sell, Ibid., 
 2 7 1305 (1905) and 29, 532 (1907). 
 
 2 Bogert and Cooke, Ibid., 28, 1449 (1906). 
 
 3 Bogert and Steiner, Ibid., 27, 1327 (1905); Bogert and Sell, Ibid., 29, 532 (1907); 
 Bogert and Klaber, Ibid., 30, 807 (1908). 
 
 4 Dehoff, /. prakt. Chem., [2] 42, 347 (1890); Thieme, Ibid., 43, 441 (1891). 
 
 5 Zacharias, Ibid., 43, 441 (1891). 
 
 8 Bogert and Chambers, THIS JOURNAL, 28, 207 (1906); Bogert and Klaber, Ibid., 
 30, 807 (1908). 
 
 7 Bogert and Sell, Ibid., 28, 884 (1906); Bogert and Cook, lloc. cit.; Bogert and 
 Klaber, Loc. cit. 
 
 8 Billow, Ber., 35, 4312 (1902); 39, 2621 and 3372 (1906). 
 
 9 Bogert and Gortner, THIS JOURNAL, 31, 943 (1909). 
 
 75 
 
790 ORGANIC AND BIOLOGICAL. 
 
 could also be condensed with amino nitrils or amino esters to the cor- 
 responding quinazolines. 1 
 
 The ease with which acylanthranils condense with primary amines to 
 crystalline quinazolines suggests the utilization of this reaction for the 
 separation and identification of easily soluble or sirupy amines difficult 
 to handle otherwise. 
 
 The same reaction was employed for the preparation of quinazoline 
 carboxylic acids from acylanthranil carboxylic acids, 2 
 
 X N.COR ,N = CR 
 
 HOOC.C e H 3 < | + zR'NH, = R^NH 3 OOC.C 4 H 3 < | + H,O. 
 
 N CO \CO . NR' 
 
 These quinazoline benzoylcarboxylic acids are colorless crystalline 
 solids, melting with decomposition above 300, more or less soluble in 
 alcohol, but very difficultly soluble in other neutral organic solvents. 
 
 From the oxalyl anthranils, quinazolinecarboxylic acids were pre- 
 pared carrying the carboxyl group on the miazine side of the nucleus, 3 
 
 .N.COCOOR .N = C.COOR 
 
 C 6 H/ | + R'NH, == C 6 H 4 < | + H,0. 
 
 N CO N CO . NR' 
 
 The particular quinazolines described in the foregoing are for the most 
 part of the type designated as 4-ketodihydroquinazolines or, more simply, 
 4-quinazolone s, 
 
 O 
 (4) 
 
 When there is an H at position 3 instead of a radical, there arises the 
 possibility of keto-enolic tautomerism, 
 
 .N = CR X N == CR 
 
 C,H/ | ^ C 6 H/ | . 
 
 X CO.NH \C(OH):N 
 
 (4-Quinazolone) (4-Hydroxyquinazoline) 
 
 All those 4-quinazolones (4-hydroxyquinazolines) which carry a hydro- 
 gen at position 3 are easily soluble in aqueous solutions of the caustic 
 alkalies and re-precipitable from such solutions by carbon dioxide or 
 acetic acid. When these alkali salts are treated with alkyl halides, the 
 3-(JV)alkyl derivative is the chief product. 4 The nitro derivatives furnish 
 an apparent exception to this, in that the product with the higher alkyl 
 halides is reported as chiefly the oxygen ether (i. e., the 4-(<9)alkyl, or 
 -OR compound). 5 We are somewhat skeptical, however, of the accuracy 
 of these results and feel that they should not be fully accepted until the 
 pure oxygen ethers have been prepared by other processes and the two 
 
 1 Bogert and Klaber, Loc. cit. 
 
 2 Bogert, Wiggin and Sinclair, THIS JOURNAL, 29, 82 (1907); Bogert and Jouard, 
 Ibid., 31, 489 (1909). 
 
 3 Bogert and Gortner, Ibid., 32, 119 (1910). 
 
 4 Bogert and May, Ibid., 31, 507 (1909). 
 
 5 Bogert and Seil, Ibid., 29, 517 (1907). 
 
 7 6 
 
RECENT INVESTIGATIONS IN THE QUINAZOLINE GROUP. 79 1 
 
 products compared. One reason for this skepticism on our part is that 
 certain of these suppositious oxygen ethers could not be hydrolyzed with 
 concentrated mineral acids (hydrochloric), a result contrary to our ex- 
 perience and to that of others working with true oxygen ethers. 
 
 Pure 3-(A^)alkyl derivatives are easily obtained by the acylanthranil 
 reaction already described. For the isomeric 4-OR derivatives, the 
 best method appears to be the treatment of the 4-chloroquinazolines 
 with sodium alcoholates. 1 In the case of the simple alkyl derivatives 
 of unsubstituted 4-quinazolones (4-hydroxyquinazolines), the (3)-NR 
 compounds are colorless, odorless solids, quite soluble in water, gen- 
 erally very difficultly volatile with steam, of higher melting point than 
 the 4-OR isomers, and are not hydrolyzed by strong hydrochloric acid. 
 On the other hand, the 4-OR compounds are oily liquids or low-melting 
 solids, usually of pleasant odor, readily volatile with steam, less soluble 
 in water but more soluble in hydrochloric acid than the NR isomers, 
 and are readily hydrolyzed by mineral acids to the hydroxyquinazoline 
 (4-quinazolone) again. Some of the lower ones can even be distilled 
 undecomposed at ordinary pressure. 
 
 In the preparation of the 4-chloroquinazolines from the 4-hydroxy- 
 quinazolines (4-quinazolones), 1 a methyl or ethyl group in position 2 
 exerts a peculiar influence upon the course of the reaction with phos- 
 phorus halides or similar halogenating reagents. In all such cases, it 
 was found impossible to replace the OH at 4 by chlorine without simul- 
 taneously introducing three chlorine atoms in the benzene part of the 
 nucleus. Even when 2,3-dimethyl-4-quinazolone was heated with phos- 
 phorus penta- and oxychlorides, 2 the 3-methyl group was split off, a Cl 
 attached itself at 4, but again three Cl's entered the benzene nucleus. 
 
 Our investigations in this 4-quinazolone group have led to the syn- 
 thesis and study of derivatives carrying the following substitutions: 
 
 1. At position, 2-, methyl, ethyl, normal and isopropyl, isobutyl, isoamyl, 
 phenyl, m- and />-nitrophenyl, benzyl, p-to\yl, COOH, and various com- 
 plex radicals and residues. 
 
 2. At position, 3-, methyl, ethyl, normal and isopropyl, iso- and second- 
 ary butyl, isoamyl, allyl, phenyl, o-tolyl, />-anisyl, benzyl, beta-naphthyl, 
 CH 2 COOR, CH 2 CONH 2 , CH 2 CN, C 6 H 4 COOR, C 6 H 4 CONH 2 , C 6 H 4 CN, the 
 amino group and its derivatives, quinazolonyls, and dimethyl dicarb- 
 ethoxy pyrrole. 
 
 3. At position, 4-, OH, Cl, and OR. 
 
 4. On the benzene nucleus-, alkyls, halogens, nitro, amino (and deriva- 
 tives), and COOH. 
 
 In the various series, where homologs of analogous structure are com- 
 pared, it will be found that the melting point falls quite steadily with 
 rise in molecular weight, the iso compounds melting higher than the 
 isomers carrying normal alkyls. This is perhaps not so surprising since 
 many series of anthranilic compounds (for example, the alkyl and acyl- 
 amino anthranilic acids, the acylanthranilic nitriles, etc.) exhibit a similar 
 behavior. 
 
 In addition to the 4-quinazolones, our studies have included also the 
 2-quinazolones (2-hydroxyquinazolines), 2,4-dihydroxyquinazolines (2,4- 
 
 1 Bogert and May, Loc. cit. 
 
 2 Compare Fischer, Ber., 32, 1297 (1899). 
 
 77 
 
792 ORGANIC AND BIOLOGICAL. 
 
 dike tote trahydroquinazolines, or benzoylene ureas), and a few other 
 types. 
 
 B. Thioquinazolines. 
 
 The work in the domain of the oxygenated quinazolines led quite natur- 
 ally to the production of bodies of analogous structure carrying sulphur 
 instead of oxygen, and known as the 4-thioquinazolone or quinazolthion (4) 
 type, 1 
 
 /N = Cr N===CR 
 
 C 6 H/ ! I C 6 H 4 < | . 
 
 \CS . NH \C(SH) : N 
 
 Since anthranilamides, as noted, easily condense to quinazolines by 
 loss of water, it seemed probable that the corresponding thioamides would 
 yield thioquinazolines. 
 
 /NH.COR X N = CR 
 
 C,H/ =C 6 H 4 < | + H.O. 
 
 \CS.NH, N CS . NH 
 
 and the results corroborated this fully. 
 
 The acylanthranilic thiamide was prepared either by first converting 
 the anthranilic nitrile to the amide by the direct addition of hydrogen 
 sulphide and then acylating, or by first acylatirig and then adding the H 2 S: 
 
 /NH, 
 
 C 6 H/ + O(COR), 
 
 A \CSNH, , 
 
 t+H,S I 
 
 /NH, | /NH.COR /N = CR 
 
 r\ TT s-\ TT S - , >. TT / I I TT \ 
 
 *\CN A* 4 ^CS.NH 2 4 \CS . NH 
 
 + O(COR), 
 NH.COR 
 
 H,S 
 
 CN 
 
 By the use of thiol acids (for example, thioacetic acid) in sealed tubes, 
 the thioquinazoline was obtained direct. The thiol acid first acylates 
 the amino group. The by-product of this acylation, H 2 S, cannot escape 
 from the tube and is thus forced to attach itself to the CN, thereby changing 
 it to the thioamide. The acylaminothioamide then passes to the thio- 
 quinazoline by loss of water. 
 
 As comparatively few thiol acids are readily available, we made our 
 reaction more widely applicable by substituting the acid anhydride with 
 sodium sulphide for the thiol acid. Thus, when anthranilic nitrile is 
 heated with acetic anhydride and sodium sulphide in open flasks or, 
 better, in sealed tubes, the anhydride first acetylates the amino group 
 with formation of acetic acid as the by-product. The latter then attacks 
 the sodium sulphide, setting free hydrogen sulphide and forming sodium 
 acetate. The hydrogen sulphide converts the acetoanthranilic nitrile 
 to the thioamide, which then splits out water and gives the quinazoline, 
 the sodium acetate possibly assisting in the elimination of this molecule 
 of water. 
 
 These thioquinazolines crystallize in beautiful yellow needles or prisms 
 
 when alcohol is used as the solvent. By virtue of the CS.NH 7""^ 
 
 C(SH) : N group, they dissolve freely in solutions of the caustic 
 
 1 Bogert, Breneman and Hand, THIS JOURNAL, 25, 372 (1903); Bogert and Hand, 
 
 Ibid., 25, 935 (1903)- 
 
 78 
 
RECENT INVESTIGATIONS IN THE QUINAZOLINE GROUP. 793 
 
 alkalies and are re precipitated therefrom by carbon dioxide or by acetic 
 acid. 
 
 Like the corresponding oxygen compounds, the melting point of the 
 2-alkyl derivatives steadily falls with rise in molecular weight, the iso 
 compounds melting higher than the isomers of normal structure. 
 
 In the course of the investigation, we have used both simple and sub- 
 stituted anthranilic acids. 
 
 C. Naphthotetrazines. 
 
 Our syntheses of the simple quinazolines having resulted so satis- 
 factorily, we decided to attempt the synthesis of compounds of the follow- 
 ing types, 
 
 N N N 
 
 N 
 . \/ \/ 
 
 N 
 ( 1,3,6,8-Naphthotetrazine) ( 1,3,7,9-Naphthotetrazine) 
 
 and in this were equally fortunate. 
 
 Naphthotetrazines of both types were prepared from the bis-acyl- 
 anthranils of the appropriate diaminophthalic acid and various primary 
 amines, 1 
 
 RCO.Nv JST.COR RC:Nv .N = CR 
 
 OCf *^CO R'N.CCK *\CO . NR' 
 
 as well as from the diaminophthalic acids themselves by reactions similar 
 to those employed for the synthesis of the simple quinazolines. The 
 diaminophthalic acids used, which must be, of course, of anthranilic 
 structure, were 
 
 HO C \/\/ NH ' H,N NH, 
 
 -_ Z -[ //NS//N ^COOH HOOC' S ^ \COOH 
 
 (3,6-Diamino-i,4-phthalic acid) (4,6-Diamino-i,3-phthalic acid) 
 These acids, as can be seen by a glance at their , graphic formulas, are 
 only double anthranilic acids, and undergo similar reactions, the former 
 yielding the 1,3,6,8-naphthotetrazines, and the latter the 1,3,7,9-isomers. 
 1,3,6,8-Naphthotetrazines were also obtained by condensing suc- 
 cinylosuccinic esters with amidines: 2 
 
 HN .HJ*OjCO.C.CH,CJOH~H N : CR 
 
 I " + ii ir ~+ i = 
 
 RC : NH_HO C.CH a C.CO:QR HJNH 
 
 HN.CO.C.CH..C.N: CR 
 
 RC:N.C.CH,.CCONH 
 
 All of these naphthotetrazine derivatives so far obtained by the above 
 processes are either infusible or melt very high. They are insoluble in 
 the ordinary neutral organic solvents. When they carry the NH.CO 
 
 1 Bogert and Nelson, THIS JOURNAL, 29, 729 (1907); Bogert and Kropff, Ibid., 
 31, 1071 (1910). 
 
 2 Bogert and Dox, Ibid., 27, 1127 and 1302 (1905). 
 
 79 
 
794 ORGANIC AND BIOLOGICAL. 
 
 x > N : C(OH) group, they dissolve readily in solutions of the 
 caustic alkalies, whence they are reprccipitated by carbon dioxide or 
 by acetic acid. 
 
 The naphthotetrazine prepared from guanidine and succinylosuccinic 
 ester gives a sodium salt crystallizing in beautiful yellow needles or prisms 
 which have a magnificent greenish fluorescence. 
 
 This, in a very hasty and imperfect way, indicates the main lines along 
 which this particular field of investigation has been developed. It would 
 only weary you to refer even hurriedly to the many subordinate lines 
 of investigation radiating from these main ones, necessitating or resulting 
 in the synthesis of many hundreds of new organic substances. I can only 
 say, as I did at the outset of this address, that it has all been most interest- 
 ing to us, and that we are still carrying on the work. 
 
 The articles published in the progress of these researches are listed 
 below. They all have appeared in The Journal of the American Chemical 
 Society, to which the volume numbers refer : 
 
 1900 i. A new synthesis in the quinazoline group. M. T. Bogert and A. H. Gotthelf, 
 THIS JOURNAL, 22, 129. 
 
 2. The direct synthesis of ketodihydroquinazolines from orthoamino acids. 
 M. T. Bogert and A. H. Gotthelf, Ibid., 22, 522. 
 
 1901 3. The synthesis of alkyl ketodihydroquinazolines from anthranilic acid. A. 
 H. Gotthelf, Ibid., 23, 611. 
 
 1902 4. The synthesis of alkyl ketodihydroquinazolines from anthranilic nitrile. 
 M. T. Bogert and W. F. Hand, Ibid., 24, 1031. 
 
 I93 5- The synthesis of alkyl thio ketodihydroquinazolines from anthranilic nitrile. 
 M. T. Bogert, H. C. Breneman and W. F. Hand, Ibid., 25, 372. 
 
 6. 3,5-Bibrom-2-aminobenzoic acid; its nitrile and the synthesis of quinazolines 
 from the latter. M. T. Bogert and W. F. Hand, Ibid., 25, 935. 
 
 1905 7. The synthesis of 5-nitro-4- ketodihydroquinazolines from 6-nitro-2-amino- 
 benzoic acid, 6-nitro-2-acetylaminobenzoic acid, and from the corresponding nitro 
 acetylanthranil. M. T. Bogert and V. J. Chambers, Ibid., 27, 649. 
 
 8. The condensation of succinylosuccinic acid diethyl ester with guanidine. 
 A derivative of 1,3,5,7-naphthotetrazine, a new heterocycle. M. T. Bogert and A. 
 W. Dox, Ibid., 27, 1127. 
 
 9. Some acyl derivatives of homoanthranilic nitrile, and the 7-methyl-4-ketodi- 
 hydroquinazolines prepared therefrom. M. T. Bogert and A. Hoffman, Ibid., 27, 
 1293. 
 
 10. The condensation of succinylosuccinic acid diethyl ester with acetamidine: 
 2,6-dimethyl-4,8-dihydroxy-9,io-dihydro-i,3,5,7-napthotetrazine. M. T. Bogert and 
 A. W. Dox, Ibid., 27, 1302. 
 
 11. The synthesis of 2-methyl-5-nitro-4-ketodihydroquinazolines from 6-nitro 
 acetanthranil and primary amines. M. T. Bogert and H. A. Seil, Ibid., 27, 1305. 
 
 12. The synthesis of 7-nitro-2-alkyl-4-ketodihydroquinazolines from 4-nitro 
 acetanthranilic acid and from 4-nitro acetanthranil. M. T. Bogert and S. H. Steiner, 
 Ibid., 27, 1327. 
 
 13. 5-Brom-2-aminobenzoic acid and some of its derivatives. M. T. Bogert and 
 W. F. Hand, Ibid., 27, 1476. 
 
 1906 14. The preparation of 6-brom-4-ketodihydroquinazolines from 5-brom-2 
 aminobenzoic acid and certain of its derivatives. M. T. Bogert and W. F. Hand, 
 Ibid,, 28, 94, 
 
 80 
 
RECENT INVESTIGATIONS IN THE QUINAZOUNE GROUP. 795 
 
 15. On 5-amino-4-ketodihydroquinazolines and 5-amino-2-methyl-4-ketodihy- 
 droquinazolines. M. T. Bogert and V. J. Chambers, Ibid., 28, 207. 
 
 16. On the condensation of succinylosuccinic esters with amidines. M. T. 
 Bogert and A. W. Box, Ibid., 28, 398. 
 
 17. On a 3-aminoquinazoline and the corresponding 3,3'-diquinazolyl, from 
 6-nitro acetanthranil and hydrazine hydrate. M. T. Bogert and H. A. Sell, Ibid., 28, 
 884. 
 
 18. Synthesis of 6-nitro-2-methyl-4-ketodihydroquinazolines from 5-nitro acetan- 
 thranil and primary amines. M. T. Bogert and E. P. Cook, Ibid., 28, 1449. 
 
 1907 19. The synthesis of quinazoline carboxylic acids from 4-aminoisophthalic acid 
 and from aminoterephthalic acid. M. T. Bogert, J. D. Wiggin and J. E. Sinclair, 
 Ibid., 29, 82. 
 
 20. A strange case of poisoning. M. T. Bogert, Ibid., 29, 239. 
 
 21. On 2,3-dialkyl-4-quinazolones and the products obtained by alkylating 
 2-alkyl-4-quinazolones (2-alkyl-4-hydroxyquinazolines). M. T. Bogert and H. A. 
 Sell, Ibid., 29, 517. 
 
 22. The synthesis of 1,3,6,8-naphthotetrazines from paradiaminoterephthalic 
 acid and from certain of its derivatives. M. T. Bogert and J. M. Nelson, Ibid., 29, 
 729. 
 
 1908 23. On certain 7-nitro-2-methyl-4-quinazolones from 4-nitroacetanthranil. M. 
 T. Bogert and W. Klaber, Ibid., 30, 807. 
 
 1909 24. 3-Amino-o-phthalic acid and certain of its derivatives. M. T. Bogert and 
 F. L. Jouard, Ibid., 31, 483. 
 
 25. On certain quinazoline oxygen ethers of the type N:C(OR) and the 
 isomeric NR.CO compounds. M. T. Bogert and C. E. May, Ibid., 31, 507. 
 
 26. On some amino and nitroamino derivatives of benzoic, metatoluic and 
 metaphthalic acids. M. T. Bogert and A. H. Kropff, Ibid., 31, 841. 
 
 27. On 2-methyl-3-amino-4-quinazolone and certain of its derivatives. M. T. 
 Bogert and R. A. Gortner, Ibid., 31, 943. 
 
 28. On 6-methyl-7-aminoquinazolones, 7-nitroquinazolone-6-carboxylic acids, 
 and 1,3,7,9-naphthotetrazines. M. T. Bogert and A. H. Kropff, Ibid., 31, 1071. 
 
 1910 29. On oxalyl anthranilic compounds and quinazolines derived therefrom. M. T. 
 Bogert and R. A. Gortner, Ibid., 32, 119. 
 
 HAVEMEYBR LABORATORIES, COLUMBIA UNIVERSITY, 
 March 2*, 1910. 
 
 A REVIEW OF DISCOVERIES ON THE MUTAROTATION OF THE 
 
 SUGARS. 1 
 
 By C. S. HUDSON. 
 Received May 9, 1910. 
 
 Dubrunfaut 2 discovered in 1846 that the specific rotation of a freshly 
 prepared cold solution of crystalline glucose decreases from an initial 
 value of about 110 to become constant at 52. This phenomenon he 
 named birotation but later discoveries have shown the name to be in- 
 appropriate and the better term mutarotation, which was introduced by 
 Lowry 3 in 1899, has generally replaced it, though the word muliirotation 
 
 1 Presented at the Second Decennial Celebration of Clark University, Worcester, 
 Mass., Sept. 15, 1909. 
 
 2 Ann. chim. phys., 18, 99-107 (1846); 21, 178-80 (1847); Compt. rend., 23, 38-44 
 (1846). 
 
 8 /. Chem. Soc., 75, 212-5 (1899). 
 
 8l 
 
890 ORGANIC AND BIOLOGIC AL,. 
 
 is also in use. In addition to glucose the following crystalline sugars 
 have been found to show mutarotation: lactose, 1 galactose, 2 arabinose, 3 
 maltose, 4 xylose, 5 fructose, 6 fucose, 7 rhamnose, 8 mannose, 9 rhodeose, 10 
 gentiobiose, 11 melibiose, 12 perseulose, 13 and several rare synthetic sugars. 
 All of these sugars reduce Fehling's solution and combine with phenyl- 
 hydrazine, proving that they are aldoses or ketoses and contain the 
 carbonyl group; on the other hand such sugars as sucrose, raffinose, 
 gentianose, and stachyose, and the polysaccharides starch, inulin, mannan, 
 etc., and the glucosides salicin, amygdalin, helicin, arbutin, etc., none 
 of which show the characteristic reactions for the carbonyl group, do not 
 exhibit mutarotation. This proves that the mutarotation is in some 
 way dependent upon the carbonyl group. 
 
 After Dubrunfaut's great discovery the next important observation on 
 mutarotation was made by E. O. Erdmann 14 in 1855, who noticed that 
 lactose occurs in two crystalline modifications, one having a higher rota- 
 tion (86) than that of the stable solutions (52), and the other a lower 
 rotation (36), and each form showing mutarotation towards the same 
 final rotation (52). Erdmann measured the rates at which each form 
 changes in rotation to that of the stable solution, but did not notice 
 that the rates are the same in value and that this fact is of much theoretical 
 significance. Many years later, after the principles of chemical dynamics 
 became better known, the author 15 showed that these equal rates prove 
 that the two changes of rotation are not different reactions but are opposite 
 parts of one balanced reaction. In this way the mutarotation of lactose, 
 and what is true of this sugar is doubtless true of all which show mutarota- 
 tion, was proved to belong to the great class of balanced reactions. 16 
 
 In 1859 Anthon 17 noticed that crystalline glucose forms its saturated 
 solutions in cold water very slowly even when the mixing is vigorous; 
 this fact was discovered for lactose by Mills and Hogarth 18 in 1879. It 
 is now known that this slowness of the process of solution is caused by the 
 same slow balanced chemical reaction, involving the carbonyl group, 
 
 1 E. O. Erdmann, Fortschritte Physik., p. 13; Fortschritte Chemie, p. 671 (1855). 
 
 2 Pasteur, Compt. rend., 42, 347-51 (1856). 
 
 3 Parcus and Tollens, Ann., 257, 160-78 (1890). 
 
 4 Soxhlet, /. prakt. Chem., 21, 283 (1880). 
 
 8 Koch, Pharm. Ztg. Riissland, 25, 619, 635, 651, 667, 683, 699, 730, 747, 763 
 (1886). 
 
 6 Jungfleisch and Grimbert, Compt. rend., 107, 390-3 (1888). 
 
 7 Guenther and Tollens, Ber., 23, 2585-6 (1890). 
 
 8 Parcus and Tollens, Loc. cit. 
 
 9 Van Ekenstein, Rec. tra-v. chim., 15, 221-4 (1896). 
 
 10 Z. Zuckerind. Bohmen, 25, 297 (1902). 
 
 11 Bourquelot and H6rissey, Ann. chim. phys. 27, 397-432 (1902). 
 11 Z. Ver. d. Zuckerind., 53, 1050-9 (1903). 
 
 13 Bertrand, Compt. rend., 147, 201-3 (1908). 
 
 14 Loc. cit. Also Ber., 13, 2180-4 (1880). 
 18 Z. physik. Chem., 44, 487-94 (1903). 
 
 18 Using the same method Meyer later proved this for glucose, Z. physik. Chem., 
 62, 74 (1908). Cf. also Roux, Ann. chim. phys., 30, 422-32 (1903). 
 
 17 Dingier** poly. /., 151, 213-23 (1859); 155, 386-8 (1860); 166, 69-71 (1862). 
 11 Proc. Roy. Soc. London, 28, 273-9 (1879). 
 
 82 
 
DISCOVERIES ON THE MUTAROTATION OF THE SUGARS. 89! 
 
 which causes the mutarotation, and that it is a general property of all the 
 aldehyde and ketone sugars. 1 
 
 The first attempt to find the physical law which governs the rate of the 
 mutarotation was made by Mills and Hogarth 2 in 1879, but the result was 
 only an empirical formula and must be regarded as unsatisfactory. It 
 is to Urech 3 that we owe the first real progress in this line. He showed 
 by a series of experiments during 1882-5 that the mutarotation follows 
 the law of unimolecular reactions. It is interesting, and to some minds 
 instructive, to note that this correct beginning in the physico-chemical 
 study of the long unsolved mutarotation reaction was coincident in time 
 with the beginning of the modern theory of solutions and chemical dynam- 
 ics. There can be little doubt that Urech's experiments, which are 
 the starting point of all exact work on mutarotation, were suggested by 
 the advances that were being made at that time in the study of chemical 
 dynamics by the new physico-chemical school. 
 
 In 1888 Brown and Morris 4 and Arrhenius 5 observed that the freezing 
 temperatures of glucose solutions remain unchanged during the process of 
 mutarotation, which proves that the reaction which causes mutarotation 
 is not a polymerization or dissociation of the sugar. More recently 
 Roth 8 has detected a slight change in freezing temperature of concentrated 
 solutions of anhydrous glucose on standing but this is doubtless due to 
 hydration and does not alter the conclusion from the work of Brown and 
 Morris and Arrhenius, because a polymerization or dissociation would also 
 affect the freezing point of dilute solutions, and the investigators are all 
 agreed that such an effect is not discernible. 
 
 In 1890 O'Sullivan and Tompson 7 noticed that the invert sugar which 
 is produced by the hydrolytic action of the enzyme invertase on sucrose 
 shows mutarotation; this fact was later investigated by E. F. Armstrong 8 
 and has been precisely studied lately by the author. 9 These researches 
 have shown that the glucose which is liberated from sucrose is a-glucose 
 and the fructose is a hitherto unknown form of this hexose, a-fructose; 
 these facts show that sucrose has the constitution a-glucose < > a-fructose. 
 The new form of fructose has not as yet been obtained crystalline. This 
 method for determining the constitution of the polysaccharides by study- 
 ing the mutarotation of the sugars which are formed by their enzymotic 
 hydrolysis was first used by E. F. Armstrong 2 in his correlation of the 
 a- and /?-methylglucosides with the a- and /?-glucoses. In applying the 
 method to other substances such as cane sugar where two mutarotating 
 sugars are formed at the same time it is necessary to extend the theoretical 
 considerations; a mathematical theory of the modified method of Arm- 
 
 1 Hudson, Z. physik. Chem., 44, 487-94 (1903); THIS JOURNAL, 26, 1065-82 (1904). 
 1 Loc. cit. 
 
 * Ber., 15, 2130-3 (1882); 16, 2270-1 (1883); 17, I547~5O (1884); 18, 3047-60 
 (1885). 
 
 * J. Chem. Soc., 53, 610-21 (1888). 
 
 6 Z. physik. Chem., 2, 491-505 (1888). 
 
 * Ibid., 43, 539-64 (1903). 
 
 7 /. Chem. Soc., 57, 920 (1890). 
 
 8 Ibid., 83, 1305-13 (1903)- 
 
 * THIS JOURNAL, 30, 1160-6, 1564-83 (1908); 31, 655-64 (1909). 
 
 83 
 
892 ORGANIC AND BIOLOGICAL. 
 
 strong and an experimental demonstration of it has recently been pub- 
 lished by the author. 1 
 
 In 1895 Charles Tanret 2 discovered a new form of crystalline glucose 
 which was found to have a specific rotation lower than that of the stable 
 solution (52), though its value increased to this on standing. This 
 discovery is the complement to Dubrunfaut's and the two must cause 
 chemists the world over to be grateful to French science, because more 
 fruitful single discoveries in the chemistry of the carbohydrates have 
 hardly been made. Tanret found the final rotation of glucose solutions 
 to be the same whether the solution is made from the higher or the lower 
 initially rotating form. He interpreted his results as proving that three 
 forms of glucose exist, one of high rotation, one of low, and the third the 
 form to which each of these changes in aqueous solution. About the same 
 time Tanret isolated similar new crystalline forms of rhamnose, galactose 
 and arabinose, and obtained Erdmann's lower rotating form of lactose 
 practically pure. Tanret's striking discoveries immediately caused new 
 interest to be taken in the problem of mutarotation. In 1899 Lowry 1 
 advanced the view that the mutarotation of glucose is caused by a balanced 
 reaction between the highest and lowest rotating forms of the sugar, a 
 view which may be expressed by the equation a-glucose ~^~*' {3-glucose. 
 This explanation is essentially different from any that preceded it and 
 later investigations have proved it to be entirely correct. On the other 
 hand, Lowry did not support this hypothesis with any direct proof and it 
 remained without such proof for several years. In 1902* the author 
 published the same view as an explanation of the mutarotation of lactose, 
 being at that time unacquainted with the publication of Lowry. The 
 explanation may be expressed by the equation a-lactose ~j~ > ' /?-lactose, 
 and experimental evidence for the view was given by measurements on 
 the heats of solution of the three forms of lactose, which showed that the 
 stable form to which a- and ^-lactose change in solution is not a chemical 
 individual, as Tanret had supposed, but is a mechanical mixture of a- 
 and /Mactoses. In 1903 the author 4 measured the slow maximum rate of 
 solution of a-lactose and showed that the slowness of dissolving, which 
 had been discovered by Mills and Hogarth, 1 is caused by the balanced 
 reaction which produces the mutarotation. By quantitative measure- 
 ments the hypothesis of the balanced reaction was tested and proved, 
 and the explanation which these measurements gave of the mutarotation 
 of lactose was immediately accepted by such an authority as Nernst. 5 
 In the same year Lowry 6 published similar experiments on glucose and 
 proved the suggestion which he had advanced in 1899. These questions 
 of priority are here stated for the reason that E. F. Armstrong 7 has recently 
 claimed for Lowry the discovery of the balanced reaction which causes 
 the mutarotation, a claim which in the opinion of the author is entirely 
 too broad. 
 
 1 Loc. cit. 
 
 2 Bull. soc. chim., 15, 195-205, 349-61; 17, 802-5. 
 * Princeton Univ. Bull., April, 1902. 
 
 4 Z. physik. Chem., 44, 487-94 (1903). 
 8 " Theoretische Chemie," ed. 1904. 
 
 6 Proc. Chem. Soc., 19, 156-7 (1903); 20, 108-9 (1904). 
 
 7 "The Simple Carbohydrates and Glucosides," p. 8. 
 
 84 
 
DISCOVERIES ON THE MUTAROTATION OF THE SUGARS. 893 
 
 A very fruitful idea was advanced by Llppmann 1 in 1895 in the sugges- 
 tion that the lactonic formula for glucose predicts two possible forms of 
 the sugar on account of the asymmetry of the end carbon atom, the two 
 structures being 
 
 , O -, /H 
 
 CH 2 OH.CHOH.CH.CHOH.CHOH.C< and 
 
 X OH 
 
 r- O n /OH 
 
 CH 2 OH.CHOH.CH.CHOH.CHOH.C<^ , 
 
 This suggestion, after a slight development by Simon, 2 was made more 
 probable by Armstrong's discovery, 3 that the a- and /9-forms of methyl 
 glucoside are hydrolyzed by enzymes to give methyl alcohol and the 
 a- and /?-forms of glucose respectively. As the methyl glucosides show no 
 aldehyde reactions the lactonic formulas have always been chosen for 
 them, the hydroxyl of the end carbon atom in the structures shown above 
 being replaced by the group OCH 3 . Armstrong's discovery indicates 
 that similar structures probably apply to the forms of glucose. This 
 suggestion received final proof in 1909 when the author* showed that certain 
 numerical relations which can only be explained by the assumption of 
 such lactonic structures for the two forms of the sugar, hold all through 
 the sugar group. If the rotation of the end carbon atom is B for one 
 structure it must be B for the other, and if A is the rotation of the 
 remaining asymmetric carbon atoms, which are common to both struc- 
 tures, the total rotation of the one structure is A + B, and of the other 
 structure A B, the difference between the two total rotations being 
 then 2B. This rotation B applies to all the aldoses because they contain 
 the same end asymmetric carbon, therefore the difference between the 
 molecular rotations of the a- and /3-forms of all the aldose sugars should 
 be a constant quantity if the sugars have the two isomeric lactonic struc- 
 tures. The molecular rotatory powers of the two forms of lactose, glucose, 
 arabinose and galactose were found indeed to differ by the quantities 
 17600, 16000, 16200, and 15700, which are sufficiently alike to show that 
 the theory is correct and that the two forms of each of the mutarotating 
 sugars have the stereomeric lactonic structures. Certain other similar 
 conclusions from the same theory were also found to agree with the 
 rotatory powers of the sugars and their glucosidic derivatives. 
 
 The catalytic action of various substances on the mutarotation reaction 
 has been investigated by various chemists. 5 These researches have 
 shown that only acids and alkalies have a strong action. Osaka 6 made 
 the first quantitative study of the relation between acidity or alkalinity 
 and catalytic action and found that the catalysis is proportional to the 
 concentration of the hydroxyl ions and proportional to the square root 
 
 1 " Die Chemie der Zuckerarten," ed. 1895, pp. 130, 990, 992. 
 
 2 Compt. rend., 132, 487-90 (1901). 
 
 3 Loc. cit. 
 
 4 THIS JOURNAL, 31, 66-86 (1909). 
 
 6 Levy, Z. physik. Chem., 17, 301-24 (1895); Trey, Ibid., 18, 193-218 (1895); 22, 
 424-63 (1897); 46, 620-719 (1903); Simon and Benard, Compt. rend., 132, 564-6 (1901); 
 Lowry, /. Chem. Soc., 83, 1314-23 (1903). 
 
 6 Z. physik. Chem., 35, 661-706 (1898). 
 
 85 
 
894 ORGANIC AND BIOLOGICAL. 
 
 of that of the hydrogen ions. Later the author 1 showed that the pro- 
 portionalities are somewhat different from this and that the rate of the 
 mutarotation of glucose is related to the acidity and alkalinity of the 
 solution by the expression rate = A + B(H') + C(OH'), where A, B, 
 and C are constants at constant temperature. This formula has lately 
 been used as the basis of a new method for measuring the electrolytic 
 dissociation of water. 2 A satisfactory explanation of the fact that acids 
 and alkalies are enormously powerful catalysts of the mutarotation while 
 all other substances are without comparable action is lacking. 
 
 The sugars glucose, lactose, galactose, rhamnose, melibiose, arabinose, 
 maltose, xylose and some others occur as monohydrates and these have 
 generally been regarded as hydrated aldehydes without lactonic structure 
 and thus intermediate forms between the two lactonic a- and/3-forms 
 of the sugars. The freshly prepared solutions of these monohydrates 
 are identical in properties with such solutions of one of the anhydrous 
 lactonic forms of the sugars and it is therefore to be concluded that the 
 equilibrium between this lactonic form, whichever it may be, and the 
 monohydrate is established instantly. For most of the sugars the lactonic 
 form which is thus in instantaneous equilibrium with the monohydrate 
 is the a-form, but for one sugar at least, maltose, it is the /3-form. The 
 mutarotation reaction may then be considered to be the slow change of 
 the monohydrate into the other lactonic form by a reversible reaction, 
 or in the form of an equation, 
 
 a-sugar + H 2 O "7"*' monohydrate ~^~^~ /?-sugar + H 3 O. 
 
 (i) .(2) 
 
 For most of the sugars the reaction i is instantaneous in comparison 
 with 2, which is therefore the mutarotation reaction, but for maltose the 
 relations are reversed. Why the monohydrate should change instantly 
 to the a-form for some sugars, but to the /9-form for others is entirely 
 unknown and is a most interesting problem. 
 
 The mutarotation reaction is general to all the aldehyde and ketone 
 sugars. It may indeed be called the fundamental reaction of the sugar 
 group. While its cause remained unknown during the half century 
 following its discovery, the last decade has brought a full explanation 
 of it. The principal facts regarding it have been accurately measured 
 and correlated. On the other hand the application of these facts to the 
 elucidation of the chemical and biological reactions of the sugars, in 
 every one of which mutarotation plays a part, has just begun, but it is 
 even now apparent that the unfolding chemistry of the polysaccharides 
 is to be largely a development of the mutarotation reaction. 
 
 BUREAU OF CHEMISTRY, U. S. DEPARTMENT OF AGRICULTURE, 
 WASHINGTON, D. C. 
 
 1 THIS JOURNAL, 29, 1571-6 (1907). 
 1 Ibid., 31, 1136-8 (1909). 
 
 86 
 
OUTLINE OF A THEORY OF ORGANIC CHEMISTRY FOUNDED ON 
 THE LAW OF ENTROPY. 1 
 
 BY ARTHUR MICHAEL. 
 Received June 27, 1910. 
 
 There appears to be no generalization in science more firmly estab- 
 lished than the second law of thermodynamics, which demands that 
 every spontaneous chemical change shall be accompanied by an increase 
 of entropy, and that the system shall endeavor to realize this increase 
 to its maximum extent. 
 
 Since the law of entropy represents the fundamental principle, under- 
 lying and regulating all chemical phenomena occurring in nature, it must 
 necessarily be the correct scientific basis for the theory of organic chemis- 
 try. But it is a curious fact that there has been as yet little attempt 
 to use this basic chemical principle in connection with organic theory; 
 this theory has been developed along lines so mechanical in their charac- 
 ter that it is perhaps no exaggeration to speak of them as essentially 
 pictorial. This unilateral, mechanical development is due largely to 
 the interpretation of the phenomenon called valency; and, if we are to 
 incorporate the law of entropy into chemical theory, it is here that our 
 theoretical conceptions will require a radical modification. 
 
 Before entering a discussion of the subject of valency, we shall men- 
 tion a conception of the chemical genesis of matter, since it prepares the 
 way for the theoretical views which follow. A simple hypothesis is to 
 assume that cosmos was originally made up of two kinds of matter, 
 which were the carriers of two kinds of chemical energy, 2 and that the 
 temperature of the system was inconceivably low. Chemical energy, 
 as it now appears to us, exists in two conditions. One of these is freely 
 and perfectly convertible into less active chemical energy and into various 
 forms of physical energy ; and this less active chemical energy can be recon- 
 verted into the active form only partially and then with comparative 
 difficulty. We shall designate the active form free, the relatively inac- 
 tive form, bound chemical energy, 3 and, as the transformations of 
 chemical energy must have obeyed the law of entropy since the 
 beginning of cosmos, the original corpuscles were exclusively carriers 
 of free chemical energy, and the accumulation of bound chemical energy 
 and the various forms of physical energy now existing have been grad- 
 ually evolved from it. 
 
 1 Address delivered at the Second Decennial Celebration of Clark University, 
 Worcester, Mass., September 15,1909. 
 
 1 To distinguish between them they will be called positive and negative, but this 
 does not imply any connection with positive and negative electricity. 
 
 8 The terms free and bound chemical energy, as here used, are not to be confused 
 with the terms free and bound energy as used in physical chemistry, with which they 
 are not identical. 
 
 87 
 
991 THEORY OF ORGANIC CHEMISTRY. 
 
 The permanence of the law of entropy justifies the conclusion that the 
 chemical relations which existed between the corpuscles at the beginning 
 were similar to those which now exist between the atoms and the mole- 
 cules. We may, therefore, assume that the free chemical energy of unlike 
 and like corpuscles united to form aggregations in which the corpuscles 
 were held together by bound chemical energy. At first the chemical 
 evolution of matter must have been accompanied by an enormous rise 
 of temperature, but later, owing to the decreasing amount of free chemical 
 energy in the cosmical system, a period must have come when the loss 
 of heat through radiation was greater than its formation, and then the 
 temperature of the system must have begun to decrease. We may 
 assume, too, that the atoms of those elements, the molecules of which 
 now show the greatest stability toward heat, were formed first and dur- 
 ing the hottest period of cosmical evolution. Hence, the atoms of hy- 
 drogen, and those of the non-metals, with small atomic weight, repre- 
 sent the earliest forms of atomic matter. 
 
 If we suppose that in the formation of the atoms of certain elements 
 the free chemical energy of the corpuscles was very largely converted 
 into bound chemical energy and heat, their atoms would be extremely 
 inert toward other atoms and incapable of uniting with each other. Such 
 elementary matter is represented by the so-called noble gases, in the 
 atoms of which the relation of free corpuscular to free atomic chemical 
 energy is analogous to that of free atomic to free molecular chemical 
 energy in the atom and molecule of nitrogen. Further, if we suppose 
 that thermic, or other conditions, toward the end of the corpuscular 
 period of chemical evolution no longer permitted a sufficient conversion 
 of free into bound chemical energy, we get a glimpse into the genesis of 
 radioactive matter, the atoms of which contain so much free corpuscular 
 chemical energy that they represent a reversible system and are, there- 
 fore, gradually breaking down into smaller parts, which then rearrange 
 according to the changed conditions of cosmos. 
 
 Kekule", 1 in his memorable paper, "Ueber die Constitution und die 
 Metamorphosen der chemischen Verbindungen, ' ' assumed that the first 
 phase in chemical union consists in molecules attracting each other 
 through their chemical affinity, and that a sort of loosely joined, larger 
 molecule is thus formed. It is obvious that the formation of this 
 "Kekule poly molecule" 2 is due to the attraction between the free chem- 
 ical energy in the constituent molecules, and that it proceeds with the 
 conversion of more or less free into bound chemical energy and heat 
 the extent of this change determining its stability. 
 
 Let us represent the free chemical energy in an atom by a point 
 
 1 Ann., 106, 141. 
 
 2 Michael, Ber., 34, 4028; 39, 2140, 2570. Am. Chem. J., 39, 3; 41, 120. 
 
 88 
 
ORGANIC AND BIOLOGICAL. 992 
 
 and the bound by a line, and let the number of the points and the length 
 of the lines be a rough indication of the changes in the energy values 
 occurring during the reaction. If we assume that the energies of un- 
 like character in a molecule of sodium and of chlorine are approximately 
 equal in value, we may represent the energy relations in sodium and 
 chlorine by 
 
 Na Na Cl Cl 
 
 and the " polymolecule, " representing the first phase in their interaction, 
 
 by 
 
 Na Na 
 
 Cl Cl 
 
 which indicates that some of the free has been converted into bound 
 chemical energy. The free chemical energies of unlike character would 
 then strive to neutralize each other as completely as possible, a phase of 
 the reaction that may be represented by 
 
 Na Na 
 
 I 
 
 Cl Cl 
 
 and then, certainly facilitated by the enormous " internal maximum heat 
 
 of reaction," 1 the bound chemical energies between Na and Na and Cl 
 and Cl would be converted into bound chemical energy between Na and 
 Cl and Na and Cl ; finally, to realize a phase which may be represented by 
 
 Na Na 
 
 I I . 
 
 Cl Cl 
 
 At this point, the bound chemical energy between the atoms of like nature 
 may be inadequate to hold them together, and the complex would then 
 break down into two molecules of NaCl. 2 
 
 What happens if we substitute magnesium in the place of sodium; 
 that is, an element the atom of which contains much less positive energy? 
 The formation of a "polymolecule," then the conversion of the free 
 chemical energy in the metallic and non-metallic atoms into bound be- 
 tween metal and halogen; but, although the energy in the sodium mole- 
 cule suffices to neutralize that in the chlorine to an extent that the com- 
 plex breaks down into two molecules, that in the much less positive mag- 
 
 1 Wohl, Ber., 40, 2290. That part of the free and bound chemical energy is con- 
 verted into heat has not been indicated. 
 
 2 The energies in two unlike atoms are never capable of exactly neutralizing 
 each other, so that a certain content of free chemical energy is invariably present in 
 the atoms of every molecule. 
 
 8 9 
 
993 THEORY OF ORGANIC CHEMISTRY. 
 
 nesium molecule is insufficient to convert enough of the bound energy 
 between the chlorine atoms into bound energy between metal and halo- 
 gens, therefore the latter atoms separate. On the other hand, the greater 
 energy in the chlorine atoms is capable of using up that in the magne- 
 sium to an extent that these fall apart. In magnesium chloride, there- 
 fore, the halogen has a considerably greater content of free chemical 
 energy than it has in sodium chloride, and bound chemical energy exists 
 not only between it and the metal, but between the chlorine atoms. We 
 may represent these relations by: 
 
 Mg<^ | " 
 
 While the energy in a molecule of magnesium is not sufficient to 
 separate the chlorine atoms, it obviously may be able to do so with the 
 less negative oxygen, and, if the opposite energies in magnesium and 
 oxygen approximately neutralize each other, two molecules of magne- 
 sium oxide should be formed. But, if we take oxygen and a metal with 
 considerably more positive energy than magnesium, say lithium, the 
 oxygen is not able to separate the metallic atoms, while the latter can 
 separate the oxygen atoms, thus leading to the formation of Li 2 O, in which 
 the Li atoms are held together by bound chemical energy. The valency 
 of an element, according to this interpretation, represents the resultant 
 of the intramolecular chemical forces acting on the atom in terms of 
 bound chemical energy, whether the action takes place directly, that is 
 through direct union of the atoms or through space; or indirectly, that 
 is, through other atoms. In as far as the free chemical energy in the 
 atoms is not so converted into bound chemical energy, it will be able to 
 exert readily a chemical attraction for such other atoms, either in the 
 same or other molecules, for which it shows a chemical affinity. 
 
 Although a spontaneous chemical change can proceed only with in- 
 crease of entropy, the increment depends on free chemical energy and 
 chemical affinity existing between those atoms, which in the reaction 
 enter into direct union with each other. The atoms in a molecule are 
 held together solely by bound chemical energy and, if their chemical nature 
 is such that their free chemical energy has very largely disappeared in 
 the formation of the molecule, the substance must be chemically inert; 
 if not, it will be more or less chemically active. Thus, the well neutral- 
 ized condition of NaCl and A1 2 O 3 , the superabundant positive energy 
 in Na 2 O, and the negative in A1C1 3 , is reflected in the properties of those 
 substances. 
 
 Let us suppose that we could isolate and experiment with ele- 
 ments other than the noble gases in atomic condition, and could pre- 
 vent the formation of molecules by the union of like, but not unlike, 
 atoms. In such a system free chemical energy would be amply present 
 
 90 
 
ORGANIC AND BIOLOGICAL. 994 
 
 and chemical union would therefore depend alone on the affinity relations 
 of the atoms. Moreover, if an isomeric substance could be formed, it 
 would be that particular isomer which would represent the maximum 
 entropy of the system under the prevailing conditions. 
 
 For instance, the present structure theory indicates the existence of 
 two isomeric cyanogen chlorides, i. e., C1NC and C1CN, but leaves us 
 entirely in doubt why only one is known. So great is the uncertainty 
 in regard to its constitution that this has long been a subject of active 
 discussion and investigation. 1 Chlorine, nitrogen and carbon in atomic 
 condition would possess ample free chemical energy for union and the 
 question which isomer would be formed would depend on the increase of 
 entropy connected with the affinity relations of Cl for N and for C. Since 
 we know that the affinity between Cl and N is exceedingly slight, and 
 that between Cl and C is large, it is absolutely certain that the isomer 
 in which the halogen is united directly to the C, i. e., C1CN, would be the 
 direct product. Furthermore, a consideration of the energetic condi- 
 tions enables us to predict the properties of the isomeric form (C1NC) ; 
 it could exist only at a very low temperature and under ordinary condi- 
 tion the rearrangement C1NC >-ClCN would occur so quickly, and 
 with such a great increase of heat that the substance would be a violent 
 explosive. 2 The matter we actually deal with is, however, in a molecular 
 condition and all chemical changes that do not proceed solely through 
 expenditure of free chemical energy involve an expenditure of energy 
 due to overcoming bound chemical energy between atoms in the molecule. 
 Chemical action is dependent, therefore, on a third factor, which con- 
 stitutes a chemical hindrance, and it can proceed spontaneously only 
 when the increase of entropy due to changes of free chemical energy 
 and affinity is greater than the expenditure of energy necessary to over- 
 come the chemical hindrance. That is, when the value of the equation : 
 chemical affinity plus free chemical energy divided by chemical hin- 
 drance, is positive. 
 
 To ascertain quantitative values for the various factors that determine 
 an organic reaction is at present impossible, but it is of the greatest im- 
 portance for the development of organic theory to be able to connect 
 
 1 See Michael and Hibbert, Ann., 364, 69. 
 
 2 It is evident that the content of free chemical energy in C1NC would be vastly 
 greater than that in C1CN, which implies a better condition of intramolecular neutral- 
 ization of the chemical forces of the atoms in the latter structure. Since such chem- 
 ical neutralization proceeds with increase of entropy, we may substitute chemical 
 neutralization in the place of entropy in the second law of thermodynamics. Further, 
 we may apply the Carnot principle to the activity of free chemical energy of unlike 
 kinds, and conclude that the increase of entropy will be greatest when the chemical 
 forces are able to neutralize each other exactly. This law of chemical neutralization 
 has the advantage over that of entropy in a much wider application to organic 
 reactions (Michael, /. prakt. Chem., [2] 60, 293; 68, 489. Ber., 38, 23). 
 
 91 
 
995 THEORY OF ORGANIC CHEMISTRY. 
 
 changes in these values with modifications in structure. This done, we 
 shall then be able to predict relative changes in the factors that contribute 
 to the entropy values and thus be able to understand and explain or- 
 ganic reactions to a degree at present impossible. 
 
 What are the properties of carbon on which the existence of this won- 
 derful and intricate organic world mainly depend? First, its capacity 
 to polymerize, to form stable chains of astonishing length; second, the 
 extreme sensitiveness of its properties to the influence of other elements, 1 
 which is shared in a 1 ke degree only by hydrogen, and which has been 
 called its "chemical plasticity"; 2 and third, its high valence combined 
 with its marked affinity for hydrogen and for most of the non-metals, 
 to form more or less stable derivatives. 
 
 The first of these properties stands clearly in a close relation to the 
 position of the element in the periodic system. In the halogen group, 
 the tendency to form greater than diatomic molecules is not shown, 
 with the exception perhaps of iodine; in the oxygen group it is shown 
 by that element, but in a far greater degree by the other members. From 
 analogy, a similar tendency to form large molecules by conversion of 
 free into bound chemical energy should be expected in passing from oxy- 
 gen to nitrogen, but the latter element acts anomalously, although in 
 the formation of its diatomic molecule its free is converted into bound 
 chemical energy to a remarkable extent. 
 
 The next member of this group, phosphorus, shows a marked capacity 
 to polymerize to large molecules, and the conversion of ordinary into 
 red phosphorus, which is accompanied by the evolution of only 19 calories, 
 is one of the most salient illustrations in chemistry of how a change of 
 free into bound chemical energy will radically change the properties of 
 a substance. The very existence of organic life depends on carbon not 
 sharing with nitrogen the property of polymerizing to a diatomic mole- 
 cule, which is poor in free chemical energy. The actual change in pass- 
 ing from N to C is similar to that in going from N to P, but it is in a de- 
 gree much more highly developed, and carbon represents among elements 
 the greatest capability to use the free chemical energy in its atom to form 
 molecules containing a large number of atoms. The midway position 
 of carbon in the second series of the periodic system indicates that there 
 is an approximate balance of positive and negative corpuscles in the 
 make-up of its atom. And, as the polymerizing capacity of non-metallic 
 atoms increases, generally speaking, with a tendency toward this con- 
 stitution of their atoms, it seems reasonable to connect this all-impor- 
 tant property of the carbon atom with its corpuscular composition. 
 
 A relation which is hardly less important for organic theory than the 
 
 1 Van't Hoff, Ansichten iiber organische Chem., I, 280; II, 242. 
 
 2 Michael, /. prakt. Chem. [2], 60, 325. 
 
 92 
 
ORGANIC AND BIOLOGICAL,. 996 
 
 foregoing, is to what extent the polymerizing power of carbon is modified 
 by the presence of other elements in the molecule, and the influence 
 which they exert on the affin ty of carbon for hydrogen and for non- 
 metals. Without exception, every element joined to carbon decreases 
 its polymerizing capacity, i. e., its affinity for itself, and the influence 
 is in the order, H, halogen, N, S and O. To the influence of the last ele- 
 ment carbon is so exceedingly sensitive that, through direct union with 
 a single atom of oxygen, the enormous combining capacity of the carbon 
 atom for itself is completely destroyed. 
 
 Notwithstanding the considerable content of free chemical energy in 
 the atoms of CO, this substance shows practically no tendency to polym- 
 erize, but the characteristic property of carbon reappears at once, 
 when the influence of oxygen is neutralized by the presence of other ele- 
 ments. Thus, the action of potassium on CO leads not to COK, but to a 
 polymerized product, derived from benzene. 
 
 Not only does O decrease the affinity of C for C, but of C for H and for 
 any non-metal to which carbon may be joined, whether the atoms are 
 directly or indirectly oined. This is true to a degree directly propor- 
 tionate to the extent of such negative influences acting on the atoms. 1 
 The capacity of hydrogen to decrease the affinity of carbon for carbon 
 is far less than that of oxygen, but it plays, nevertheless, an important 
 role in many organic reactions. Thus, the pinacone >-pinaco- 
 line rearrangement : (H 3 C) 2 = C(OH) (HO)C = (CH 3 ) 2 > (CH 3 ) 3 = 
 C CO CH 3 + H 2 O, takes place on boiling with dilute mineral acid, and the 
 
 1 Michael, /. prakt. Chem., 37, 473; 60, 286. Ber., 38, 28, 3221. The writer is 
 unaware of any facts in organic chemistry which are not strictly in accordance with 
 the above stated rule. W. A. Noyes (Tins JOURNAL, 31, 1371) believes that the 
 greater instability of acetoacetic acid (CH 3 COCH 2 CO 2 H) over pyrotartaric acid 
 (CH 3 COCO 2 H) "is some slight indication that the separation of the carbon atoms 
 is ionic in character, taking place more readily when there is a greater contrast be- 
 tween the atoms united together." In the first-named acid, the group C CO 2 H is 
 under the influence of H 2 and a negative, acidic radical (CH 3 CO), in the second under 
 a positive radical (CH 3 ) and O and it is quite in agreement with the above rule that 
 acetoacetic acid splits off CO 2 much more readily than pyrotartaric acid. The writer, 
 also, knows of no satisfactory evidence in favor of the view that any strictly organic 
 reaction is ionic in character (see Michael, Ber., 38, 29; Am. Chem. J., 43, 322; Michael 
 and Hibbert, Ber., 31, 1090); or of any facts that are more easily understood than 
 otherwise by such an assumption. The formation of ethyl chloride from ethyl alcohol 
 and phosphorus pentachloride, while phenol gives partly chlorobenzene, partly phenyl 
 phosphate, is mentioned by Noyes (loc. tit., 1370) as confirming this view. However, 
 when we consider that the chemical hindrance to the formation of a chloride, i. e., 
 the energy necessary to separate hydroxyl from the hydrocarbon radical, is much 
 greater with phenol than with ethyl alcohol, it is obvious that such assumptions as 
 that phenol can ionize to the phenyl and hydroxyl group, and that ethyl alcohol 
 can ionize to ethyl and hydroxyl, do not contribute in any way to make the subject 
 more clear. 
 
 93 
 
997 THEORY OF ORGANIC CHEMISTRY. 
 
 reaction apparently should lead, with loss of water, to the formation of 
 tetramethylethylene oxide. 
 
 This compound contains a three-membered, cyclic chain, which is 
 formed under considerable tension, and, besides, a large number (12) 
 of hydrogen atoms, exerting in a very important position (3) their posi- 
 tive influence on the cyclic carbons. Such a structure cannot represent 
 a very stable substance. On the one hand, there is considerable tension, 
 representing energy in a potential condition; on the other, an extremely 
 insufficient, intramolecular chemical neutralization of the positive by 
 the negative energy in its atoms. The compound may, indeed, be com- 
 pared to sodium oxide, and shares with that substance a capacity to 
 unite with water, most energetically, and with great increase of entropy. 
 It is apparent that the oxide cannot possibly be formed from pinacone 
 under the conditions of the reaction, but, if a rearrangement may lead 
 to the formation of an intramolecularly well neutralized substance, this 
 may be formed, provided the increase of entropy due to the intramol- 
 ecular neutralization is greater than the decrease that is due to the 
 chemical hindrance, *. e,, the energy necessary to effect the migration of 
 a methyl group. These conditions are possible, for pinacoline repre- 
 sents a fairly well neutralized structure and has, consequently, a con- 
 siderable heat of formation; 1 and the expenditure of energy accompany- 
 ing the migration of a methyl in pinacone is comparatively small, owing 
 to the decrease of the affinity of carbon for carbon by the influence of the 
 numerous hydrogens. 
 
 That phenyl exerts an extremely strong positive influence on any atom 
 joined directly to it 2 is evident from the fact that two such groups united 
 directly with iodine, give that non-metal a metallic character. It might, 
 therefore, have been expected, that the accumulation of phenyl groups 
 would facilitate rearrangements of the nature of the pinacone > pina- 
 coline reaction, as this has been especially proven by the investigations 
 of Tiffeneau. We have, moreover, direct experimental evidence that 
 hydrogen diminishes the affinity of carbon for carbon hi the observa- 
 tion of Acree, 3 that in the rearrangement with di-/j-tolyldiphenylpinacone 
 it is the more positive tolyl radical that migrates. 
 
 Another interesting illustration of this influence of hydrogen is found 
 in that much-discussed substance "triphenylmethyl" (hexaphenyl- 
 ethane). Tshitshibabin 4 has shown that replacement of five of the 
 hydrogens in ethane by phenyl groups materially lessens the affinity 
 of the ethane carbon atoms for each other. It is, therefore, not surpris- 
 
 1 Zoubuff, Chem. Centralbl. t 99, I, 516. 
 
 2 Michael and Leigh ton, Ber., 39, 2792. 
 8 Am. Chem. J., 33, 180. 
 
 4 Ber., 40, 367. 
 
 94 
 
ORGANIC AND BIOLOGICAL. 998 
 
 ing that when the remaining hydrogen is likewise replaced, the mutual 
 affinity of these carbons is so greatly diminished that the substance 
 easily dissociates into two molecules of triphenylmethyl, 1 and that these 
 carbons, or the. carbon, in "triphenylmethyl" joined to the three phenyl 
 groups, have chemical properties similar to those of a very positive metal, 
 for instance, sodium. 2 Nor is it surprising that hexaphenylethane may 
 undergo easily a desmotropic rearrangement into the quinoid form : 
 
 ' 
 
 - 
 
 (C 6 H 5 ) 2 =C=< X 
 
 'N 
 
 or, since the difference in the entropy values of these two forms is slight, 
 that the existence of one or the other form, or a derivative, will depend 
 on the nature of a reagent or even of a solvent. 8 
 
 The remaining fundamental properties of carbon, its high valency 
 and its capability to combine not only with hydrogen but with most of 
 the non-metals to form stable derivatives, are also related to the posi- 
 tion of the element in the periodic system. An element acts as mono- 
 valent towards H, or Cl, when its energy suffices to neutralize that of H, 
 or Cl, to an extent that the system is incapable of uniting with further 
 
 1 Since the above was written Schlenk (Ann., 372, i) has shown that with a more 
 positive radical than phenyl, i. e., biphenyl, the affinity of carbon for carbon is reduced 
 to such an extent that tribiphenylmethyl exists in solution in mono-molecular 
 condition, which is a further confirmation of the above explanation. 
 
 1 Michael, /. prakt. Chem., [2] 60, 423, 428; 64, 107; Ber., 39, 2791. 
 
 'Michael and Hibbert, Ber., 41, 1091. A thermochemical investigation on 
 intramolecular rearrangement will be published later; it may be stated that 
 all our present experimental data on this subject confirm the view that the 
 fundamental reason of the phenomenon is the increase of entropy proceeding 
 with the change. In intramolecular changes it is the formation of an iso- 
 mer with a greater heat of formation and in intermolecular rearrangements 
 the increase of entropy is connected with a change in composition and the reagent 
 uniting with a product of decomposition; in either case, slight chemical or physical 
 forces may bring about the change, if the chemical hindrance is inconsiderable (see 
 Michael and Hibbert, Ber., 41, 1091). The rearrangements of camphor on treatment 
 with P.p 4 and H 2 SO 4 , to which W. A. Noyes (Tnis JOURNAL, 31, 1372) recently called 
 attention, may be understood from the point of view here presented. In camphor 
 the affinity of the central carbon to those with which it is directly joined has been di- 
 minished considerably by the influence of hydrocarbon radicals and the central ring 
 appears to exist in a condition of tension; moreover, such reduced benzene derivatives 
 show a tendency to pass over into benzene derivatives, as the formation of the para- 
 bonds in benzene is connected with a considerable increase of entropy (Michael, /. 
 prakt. Chem., [2] 79, 418). Phosphoric anhydride is a powerful dehydrating agent 
 and the formation of a benzene derivative (cymene) with the elimination of water 
 and rupture of a central carbon bond represents the maximum increase of entropy. 
 In its action on camphor sulphuric acid acts not only as a hydrolyzing, but also as an 
 oxidizing agent; the formation of />-acetyl-o-xylene undoubtedly represents the max- 
 imum entropy under such conditioms. 
 
 95 
 
999 THEORY OF ORGANIC CHEMISTRY. 
 
 atoms of these elements. In passing from F to O, from O to N, and from 
 N to C, the valency for H, or Cl, increases, because the amount of energy 
 in these atoms, able to neutralize that of H, or Cl, is successively de- 
 creasing. CH 4 or CC1 4 represent stable substances, because the energy 
 and affinity relations between C and H, or Cl, are such that, in the com- 
 bination of four atoms of hydrogen or chlorine among themselves and 
 with one atom of carbon, comparatively little free chemical energy re- 
 mains in any of the atoms. 1 
 
 Like the polymerizing capacity and the "chemical plasticity" of car- 
 bon, its power to unite not only with hydrogen, but with most non- 
 metals, is due to the approximate balance of the positive and negative 
 corpuscular energies in its atom. The direction in which the affinity of 
 carbon for such elements will vary under the influence of other atoms 
 in the molecule must be toward those of elements adjacent to it in the 
 periodic system. Thus, the effect of increasing the influence of H on C 
 in relation to H, or to a non-metal, joined to it, must be to shift its affinity 
 values toward those of silicon, i. e., there should be a decrease in the 
 value for H and an increase for that of a non-metal. On the other hand, 
 increasing the influence of O should shift them towards those of N, i. e., 
 decrease the values both for H and a non-metal. Further, the effect of 
 such changes on the content of free chemical energy of C, and of any 
 atom joined to it, must stand in a direct relation to the changes in the 
 affinity values; in fact, the free must respond to such changes before the 
 bound chemical energy. 
 
 According to van't Hoff, 2 two atoms in a molecule acting through di- 
 rect union or through space, or indirectly, that is through intermediate 
 atoms. This idea has been further developed 3 and shown to be of great 
 importance in explaining organic reactions. If we number a certain 
 atom in any fatty compound with a normal carbon chain by the figure i, 
 our present knowledge of the combined mutual influence between this 
 atom and others in the molecule is expressed by the following "scale of 
 combined influence," the numbers indicating the degree of removal and the 
 extent of the influence decreasing in the order given : 2 3 5 6 4 7 
 
 1 Replacement of an H in CH 4 by Na gives a substance with preponderance of 
 positive energy, and which is, therefore, poorly neutralized intramolecularly. Car- 
 bon, a weak non-metal, in uniting with very positive metals, tends to form compounds 
 of the type C 2 Me, in which the accumulated negative energy of several carbon atoms 
 endeavors to neutralize the positive energy of the metal. Only with a weak positive 
 metal like Al are metallic derivatives of methane formed, and it is doubtless owing 
 to this relation between the energies of C and Al, the compounds of which are so widely 
 distributed in nature, that we owe the occurrence of such enormous deposits of satura- 
 ted hydrocarbons. 
 
 2 Ansichten tieber die organische Chemie, I, 284-285; II, 252-254. 
 
 Michael, /. prakt. Chem., [2] 60, 331. Ber., 39, 2138-2157, 2780-2790; 40, 
 141. 
 
 96 
 
ORGANIC AND BIOLOGICAL. IOOO 
 
 (9 10 n) 8. It is to be strongly emphasized that the effect of an 
 atom in position 2 or 3 is far greater than that of any similar atom less 
 closely connected, and, in the case of atoms farther removed, the in- 
 fluence must be largely direct, i. e., spatial. 
 
 The principles developed above form a new basis for the theory of 
 organic chemistry and may be applied to any problem arising in the 
 science. 
 
 Several important organic questions will be discussed from the new 
 point of view. One of the weakest sides of the present structure theory 
 is that it indicates the existence of a countless number of compounds, 
 which are incapable of existence. One instance, that of an isomeric 
 chloride of cyanogen (C1NC) has been already discussed, but this ques- 
 tion is of such importance that it will be considered with substances of 
 a different type. Nitrosomethane (H 3 CNO) does not exist, as it passes 
 over spontaneously into the isomeric oxime: H 3 C NO > H 2 C= 
 N(OH). If we add an oxygen to the nitroso group, we obtain nitro- 
 methane (H 3 CNO 2 ), which is perfectly stable, but the tautomeric form of 
 which (H 2 C = NO(OH)) is so unstable, that its existence can be proven 
 only by indirect means. The thermochemical equation, 2 NO 4- O 2 = 
 2NO 2 + 26.9 cal. proves conclusively that the nitroso group contains 
 much more free chemical energy than the nitro, which is the reason why 
 the nitroso group in nitrosobenzene is so much more reactive than the 
 nitro group in nitrobenzene. In nitrosomethane, then, the following 
 energetic and affinity relations exist: the oxygen has much free chem- 
 ical energy and a strong affinity for the H of the methyl group, and by 
 the change into the oxime, the great content of free chemical energy in 
 the nitroso group is largely converted into bound chemical energy and 
 heat. The transformation therefore proceeds with increase of entropy 
 and the oxime represents an intramolecularly well neutralized structure, 
 which agrees with its amphoteric properties and the slight additive capacity 
 at the double bond. Since the nitro group in nitromethane has less free 
 chemical energy than the nitroso in nitrosomethane, its oxygen has less 
 capability to overcome the bound chemical energy holding the hydrogen 
 to the carbon. A rearrangement to isonitromethane is barred for a sec- 
 ond reason, viz., that it would proceed with a degradation of entropy, 
 for it is evident that the neutral nitromethane, the nitro group of which 
 carries but little free chemical energy, is vastly poorer in such energy 
 than the strongly acidic, unstaturated isonitromethane. 1 
 
 In order that a rearrangement should proceed spontaneously, the atom 
 
 which receives the migrating atom, or group, must have sufficient affinity 
 
 for it to be able to overcome the bound chemical energy between the 
 
 migrating atom, or group, and the atom to which it is already joined. 
 
 1 See Ann., 363, 21. 
 
 97 
 
100 1 THEORY OF ORGANIC CHEMISTRY- 
 
 If we increase through a structural change the bound chemical energy 
 more than we do the affinity and free chemical energy factor; or if 
 we decrease the latter without essentially altering the former, 
 we obviously increase the relative stability of the new derivative and 
 it may show an existence in a free state. Through certain structural 
 changes the difference between the entropy values of the isomeric forms 
 may be lessened, and we may arrive in this way to desmotropic sub- 
 stances, the energy relations of which are so evenly balanced that the 
 existence of one or the other form may be determined by a slight expen- 
 diture of extraneous chemical, or physical energy. 1 
 
 Before 1887 the substitution process in organic chemistry was uni- 
 versally supposed to consist of the direct replacement of an atom, or 
 group, by another. It was then shown, by an investigation on the con- 
 stitution of acetoacetic ester and its sodium derivative, 2 that this view 
 could be upheld no longer and that apparent substitution is often the re- 
 sult of a combination of an addition and elimination process. Subse- 
 quent researches 3 have shown that substitution, as represented by the 
 old view is of comparatively rare occurrence, and that a rational inter- 
 pretation of the process may be based on the entropy principle. Thus, 
 by the use of a metal like sodium, which has considerable free chemical 
 energy and a strong affinity for oxygen, the hydrogen in CH 2 = NOH 
 attached directly to oxygen may be driven out, with the formation of 
 CH 2 = NONa. 4 This change is only apparently a direct replacement 
 of hydrogen by sodium, for what actually occurs is, that the energy and 
 affinity values of the metal are such that it is able to overcome the bound 
 chemical energy between the oxygen and hydrogen and that the latter 
 element is driven out, not replaced. 
 
 The distinction between replacing and driving out may seem from the 
 above instance to be unimportant, but it is in reality of fundamental 
 importance in organic reactions. Let us consider, for instance, the be- 
 havior of nitromethane and hydrocyanic acid towards sodium from the 
 new point of view! In the system 
 
 1 Michael, Ann., 363, 27. 
 
 2 Michael, /. prakt. Chem. [2], 37, 473. 
 
 8 Michael, Loc. cit., 60, 316. Ber., 33, 3739; 34, 4028; 38, 22, 1922-1938, 2083, 
 2097, 3218. Amer. Chem. ]., 43, 330. 
 
 * It does not follow from the formation of this sodium derivative that the change 
 
 as represented by CH 2 =NOH > CH Z =NONa designates an increase of entropy; 
 
 indeed, a consideration of the well neutralized, amphoteric character of the oxime 
 and the strong basic, easily hydrolyzed character of the sodium derivative, leaves no 
 doubt that the free chemical energy in the latter is much greater than in the former 
 structure. In the reaction much of the free chemical energy in sodium is converted 
 into bound; it is the total change (2CH 2 =NOH + Na., = 2CH, =NONa + H 3 ) 
 that proceeds with increase of entropy. 
 
ORGANIC AND BIOLOGICAL. IOO2 
 
 / 
 H S C-N< | + Na, 
 
 > 
 
 the metal may be attracted either by the C or the O, but not only is the free 
 chemical energy in the O larger than that in the C, but also the chemical 
 affinity for Na. Moreover, according to the law of entropy, the system 
 must strive to realize the maximum condition, which will be the formation 
 of a sodium derivative, in which the free chemical energy existing in nitro- 
 methane and in sodium is converted as completely as possible into bound 
 chemical energy and heat. This condition is realized by the direct union 
 of Na with O, since then an almost neutral salt will be formed, while the 
 derivative containing the metal joined directly to C would be strongly 
 basic and have positive energy in great excess. Indeed, if such a deriva- 
 tive as NaCH 2 NO 2 could be obtained at a low temperature, it would pass 
 over at ordinary temperature spontaneously and with an enormous in, 
 crease of entropy into CH 2 = N(ONa)O. 1 The intramolecular hindrance- 
 which nitromethane offers to attack, of the Na on the O is the energy 
 necessary to overcome the bound chemical energy between a hydrogen 
 and the carbon, which, owing to the strong negative character of the 
 nitro group, is very considerably less than in methane and the reaction 
 therefore proceeds readily. 
 
 According to the old substitution theory, the action of Na on HCN 2 
 proceeds by the direct replacement of the hydrogen by the metal, form- 
 ing NaCN; according to the new theory, the Na may be attracted by 
 the C or the N, and a salt may be formed if the metal is able to overcome 
 the bound chemical energy between the H and the C and the reaction 
 proceeds with an increase of entropy. The properties of the cyano group 
 leave no doubt as to the existence of considerable free chemical energy 
 in the C and the N, and there is also no doubt that Na has a greater affinity 
 for N than for C: furthermore, N, being an element with more negative 
 chemical energy than C, the energy of the metal in NaNC is much better 
 neutralized than it would be in NaCN. The energy and affinity condi- 
 tions permit, therefore, hi the direct formation of CH 2 = NO(ONa) and 
 NaNC, the maximum possible increase of entropy, and any other con- 
 ception of the structures of these salts, is as inconceivable from the new 
 theory, as the older view leaves us wholly in the dark in regard to them. 
 
 1 Although a "double" bond is usually an indication of the accumulation of free 
 chemical energy, its symbolistic use for this purpose would be misleading. The free 
 chemical energy in an atom must vary with the extent of intramolecular neutralization/ 
 *'. e., in CH 2 = NO(ONa) the free chemical energy at C and N is used up indi- 
 rectly to a very considerable extent in neutralizing the positive energy of the sodium. 
 An approximate idea of the free chemical energy in the atoms of a molecule can usually 
 be formed by a consideration of their chemical nature, the structure and the proper- 
 ties of the substance. 
 
 2 Michael and Hibbert, Ann., 364, 64. 
 
 99 
 
ioo3 THEORY OF ORGANIC CHEMISTRY. 
 
 We have seen that the positive energy in sodium has been largely 
 converted into bound chemical energy, when the metal is introduced 
 into nitromethane and that neither at the unsaturated carbon or nitrogen 
 of H 2 C = N(ONa)O is there much free chemical energy. It follows from 
 these energy conditions that this salt should not easily react with a re- 
 agent, unless the latter contains atoms with much free chemical energy 
 and a large affinity value for certain atoms in the salt. Hence, sodium 
 isonitromethane is comparatively inert toward methyl iodide: but, if we 
 make a change hi the structure of the salt, so that the metal is less well 
 neutralized, we shall facilitate the reaction ; for, by doing so, we increase 
 not only the free chemical energy of the unsaturated atoms, but the 
 difference between the heats of formation of sodium iodide and the sodium 
 salt, which is one of the largest factors in determining the entropy of 
 the reaction. The conditions for an easy reaction are fulfilled, for instance, 
 in sodium acetoacetic ester (CH 3 CONa = CH COOCsH 5 ), for in this 
 derivative the positive energy of the metal is very inadequately neutral- 
 ized by the weakly acidic organic radical to which it is joined, and the 
 unequal balance between the positive and negative chemical forces must 
 leave considerable free chemical energy in the unsaturated atoms. The 
 reaction may proceed in two directions: 
 
 CH, CONa > I 
 
 I. || I = CH 3 CO-CH(CH S ) COOC 7 H 5 + Nal. 
 
 H 5 C 2 OOC-CH < CH 5 
 
 H S C Na > I 
 
 II. Ill s=CH, C(OCH,)=CH COQC-Hj-fNat 
 
 H 5 C,OOC CH=C O < CH S 
 
 It is of interest to analyze the energy and affinity relations of the un- 
 saturated carbon joined directly to the carbethoxyl group and those of 
 the oxygen joined to sodium, since they determine the course of the re- 
 action. Sodium iodide is formed in either case, and, as the heat of forma- 
 tion of theC- is greater than that of theO-methyl derivative, 1 its forma- 
 tion represents the maximum entropy of the system. The introduction 
 of sodium into acetoacetic ester (CH 3 CO CH 2 COOC^) has the 
 following effect on the energy and affinity relations of the carbonyl oxy- 
 gen (in CO) and the methylene carbon (hi CH 2 ) : 
 
 First, the free chemical energy in the O has been greatly decreased 
 through direct union with the metal, while part of the bound chemical 
 energy of the C (used before in holding the eliminated H) has been con- 
 verted into free; second, the affinity of the O for CH 3 has been greatly 
 reduced by the positive influence of the metal, which, on the other hand, 
 has neutralized the effect of the two negative radicals (CH 3 CO and 
 COOCjHj) and given the unsaturated a-C a large affinity value for methyl. 
 It is evident that when we take the entropy, energy and affinity relations 
 1 Experimental proof will be published later. 
 
 IOO 
 
ORGANIC AND BIOLOGICAL. IOO4 
 
 into consideration, the conversion of the O-sodium salt into the C-methyl 
 derivative, *. e., the reaction represented by I, is not an abnormal, but a 
 perfectly normal, reaction, 1 as, indeed is every chemical change hi which 
 the condition of maximum entropy is realized. 
 
 Finally, we shall discuss another fundamental organic process, that of 
 addition, from the standpoint of the second law of thermodynamics. 
 
 If we remove one hydrogen from two adjacent hydrocarbon groups 
 in propane a compound is formed (CH 3 CH = CH 2 ) in which part of 
 the bound chemical energy previously holding the eliminated hydrogen 
 atoms hi chemical union appears as free chemical energy at the unsatura- 
 ted C-atoms. 2 In the addition of a reagent to such a compound, the 
 free chemical energy of the unsaturated atoms is more or less completely 
 converted into bound chemical energy and heat, and the second law of 
 thermodynamics compels the addition to take place hi such a manner 
 that the maximum entropy will be realized, unless there is some chemical 
 hindrance, which prevents this attainment of the ultimate goal of free 
 chemical energy. 
 
 The structure theory teaches us that in the addition of hydrobromic acid 
 to propene, two isomers (propyl and isopropyl bromide) may be formed, but 
 it fails altogether to give us any indication which of these products, or 
 whether both of them, should result. The chemical hindrance hi this reac- 
 tion is the energy necessary to overcome the bound chemical energy between 
 the H and the Br of HBr to the extent to which it exists between them 
 in the bromopropane that will be formed in the addition. 3 This hindrance 
 is obviously quantitatively the same in the formation of either isomer. 
 The maximum entropy hi this addition will be attained, therefore, hi 
 the formation of the isomeric bromopropane with the greater heat of forma- 
 tion. 
 
 Obviously, it is of great importance in this and hi many other organic 
 reactions to be able to trace the relation between the structure of iso- 
 mers and their heat of formation. This is enabled by the following 
 " thermochemical law of structure." 4 In isomers with normal chains 
 and which contain a common negative radical as a nucleus, that isomer 
 will have the largest heat of formation, the positive radicals of which to 
 the greatest extent are under the influence direct and indirect of the 
 negative nucleus. Thus, in propyl and isopropyl bromide the common 
 negative nucleus is CBr, which hi the last compound is under the direct 
 influence of two methyl groups, while in propyl bromide only one methyl 
 is directly, the other indirectly, joined. The intramolecular neutraliza- 
 
 1 Michael, Ber., 38, 129. 
 
 1 /. prakt. Chem., [2] 60, 298. 
 
 * Michael, Am. Chem. ] ., 43, 333 (foot-note). 
 
 4 Michael, /. prakt. Chem., [2] 68, 499; 79, 418; Ber., 39, 2140. 
 
 101 
 
1005 THEORY OP ORGANIC CHEMISTRY. 
 
 tion, which finds an expression in the heat of formation, is therefore 
 larger in the iso than in the normal bromide, and, since the thermic 
 value of direct is very much greater than that of indirect chemical 
 union, the heat of formation of the former compound is considerably 
 larger than that of the latter. 
 
 Not only does the system, propene and hydrobromic acid, realize its 
 maximum condition of entropy in the formation of isopropyl bromide, but 
 the affinity relations at the points of maximum concentration of the free 
 chemical energy, i. e., at the unsaturated carbons, are such as to favor the 
 course of the reaction in this direction, since the influence of methyl in 
 this substance is positive to that of hydrogen in the same position. 1 This 
 relation causes in propene a greater accumulation of positive energy at the 
 middle than at the end unsaturated carbon and the middle carbon must 
 have, therefore, the greater affinity for the strongly negative halogen of the 
 acid. It seems theoretically probable that this coincidence of affinity and 
 entropy values should lead exclusively to the formation of the iso deriva- 
 tive, as, indeed, it would if chemical change depended solely on the free 
 energy and the affinity values. When a mixture, containing an acid 
 with a very large and a very small .acidity constant, is brought together 
 with a quantity of a strong base inadequate for complete neutralization 
 of the acids present, there is always an appreciable amount of salt de- 
 rived from the weak acid formed. The chemical force in each acid en- 
 deavors to its utmost capacity to contribute its share toward the increase 
 of entropy, which depends not only on the values of the affinity constants 
 but, although to a very much smaller degree, on the actual mass, by weight, 
 of acid present. 
 
 If the formation of normal propyl bromide from propene and hydro- 
 bromic acid proceeds with an increase of entropy, which it undoubtedly 
 does, we have in this addition reaction two chemical forces, each striving 
 to increase the entropy, but, in this case, the mass by weight cannot be 
 changed and the struggle is between energies. 2 Furthermore, since 
 there is no difference in the chemical hindrance to the addition in 
 either direction, it is extremely probable that the relative amounts of 
 salts, or isomeric bromides, formed will stand in a direct relation to the 
 increase of entropy, and as this is very much greater with the formation 
 of isopropyl bromide, it agrees with the theory that the normal bromide 
 is formed only to a very slight extent. 3 
 
 The principle here involved was first used by Thomson 4 to determine 
 the relative acidity constants, and has been called the "principle of 
 
 1 Michael, /. prakt. Chem., [2] 60, 332; Ber., 39, 2142 (footnote). 
 
 2 There is no practical difference, as matter from a chemical point of view should 
 be considered only as a carrier of chemical energy. 
 
 3 Michael and Leigh ton, /. prakt. Chem., 60, 443. 
 
 4 Pogg. Ann., 138, 497. 
 
 102 
 
ORGANIC AND BIOLOGICAL,. IOO6 
 
 partition"; 1 it may be applied to every organic reaction where two or 
 more isomers may be formed. 2 Let us take, as illustrations of the appli- 
 cation of this principle, the addition of water by means of sulphuric acid 
 to hexine-i and -2. In hexine-i (CH 3 CH 2 CH 2 CH 2 CEE CH), 
 we have practically the same conditions as in propene, that is, the differ- 
 ence between the energy and affinity values of the unsaturated carbons 
 are due to the difference between the direct influence of an alkyl group 
 and a hydrogen; hexanone-2 (CH 3 CH 2 CH 2 CH 2 CO CH 3 ) and 
 probably a very slight amount of hexanal (CH 3 CH 2 CH 2 CH 2 
 CH 2 CHO) are formed. The relations in hexine-2 (CH 3 CH 2 CH 2 
 C EE C CH 3 ) are quite different; the unsaturated carbons are both joined 
 directly to alkyl groups, and the change in their energy values is due 
 not to direct, but to indirect, influences, which are largely spatial. This 
 relation must cause the heats of formation of the products that may 
 result, hexanone-2 and -3, to be much nearer together than the isomers 
 that may be formed in the addition to hexine-i ; also an approximation 
 in the energy and affinity values at the unsaturated carbons. 
 
 According to the "principle of partition," the relative amounts of 
 hexanone-2 and -3 formed should not fall very far apart. Moreover, 
 we can approximately estimate the energy values of the unsaturated 
 carbons in relative terms by the use of the "scale of combined influence" 
 mentioned above. Applying this scale to the relations in hexine-2, 
 omitting those atoms the influences of which on the unsaturated carbons 
 are equal, 2 or very nearly so, we find that A^ C 3 (joined directly to 
 methyl) is under the influence of one carbon in the 4th, one hydrogen in 
 the 3rd, and three hydrogens in the 5th position, and A r C (joined di- 
 rectly to butyl) has one carbon acting in the 3rd and 4 hydrogens in the 
 4th position. Since atoms in the 3rd and 5th positions exert a greater 
 influence than those in the 4th, it is obvious that the positive energy 
 at A^ C is greater than that at A r C, and that a larger proportion 
 of that ketone should be formed, when the negative part of the addenda 
 adds to it, i. <?., hexanone-2. A re-investigation 4 of the reaction shows 
 indeed that about 60 per cent, of hexanone-2 to 40 per cent, of -3 are 
 formed in the reaction. 
 
 The present structure theory has been, and always will be, of inestimable 
 service to organic chemistry: it has taught us, until recently, 5 the possi- 
 ble number of isomers that may exist of a given formula, and it has been 
 a guide in determining the constitution of most of the substances that 
 
 1 Michael, J. prakt. Chem., [2] 60, 341-354; Ber., 39, 2138-2156, 2569, 2786- 
 2 795; 40, 140. 
 
 2 See J. prakt. Chem., 60, 341. Ber., 39, 2141. 
 
 * The capital "Delta" denotes unsaturation (Baeyer, Ann., 245, 112). 
 4 Michael, Ber., 39, 2133. 
 8 Ber., 39, 203. 
 
 103 
 
1007 THEORY OF ORGANIC CHEMISTRY. 
 
 have been discovered. But its weakness and limitations are inherent 
 in its foundation on a mechanical conception of valency and an almost 
 exclusive theoretical development along similar lines, for surely in nature 
 there are no forces more intimately and indissolubly connected with 
 changes in energy than the chemical. 
 
 Largely for this reason, the structure theory fails to offer explanations 
 for many of the simplest organic reactions and, for many years, it has 
 failed in explaining and co-ordinating with theory much of the wonder- 
 ful experimental progress that has been made in the science. 
 
 It is true that innumerable attempts have been made to amplify or 
 change the idea of valency and the structure theory so as to remedy 
 these deficiencies, but they have always been along mechanical lines and 
 have led to such impossible theoretical conceptions as new brands of 
 valencies, dissociated and partial valencies, oxonium and carbonium 
 theories, steric hindrance due to size of the atoms, etc., etc. 
 
 All the forces in nature, whether mechanical or chemical, have the 
 same goal in view, which is the realization of the maximum condition of 
 entropy, and a scientific theory of chemistry must inevitably have this 
 law as its basis. The present aim of organic theory is not to abandon 
 the structure theory, but so to broaden and develop it that it becomes a 
 consistent and harmonious part of nature. 
 
 NEWTON CENTRE, MASS. 
 
 PROGRESS IN SYSTEMATIC QUALITATIVE ORGANIC ANALYSIS. 1 
 
 BY S. P. MULLIKEN. 
 
 Received June 29, 1910. 
 
 A general procedure in organic qualitative analysis that may be trusted 
 to lead to the discovery of the proximate composition of any unknown 
 organic substance whatever, whether this be a simple compound or a 
 mixture, is demonstrably incapable of practical realization. Before pro- 
 ceeding to the discussion of the main subject of this paper, it therefore 
 behooves us to pause for a moment to note certain limits which Nature 
 seems to have set against the too curious advances of the analyst. 
 
 The most clearly insuperable of these limitations are associated with 
 high molecular weight. If a paraffin hydrocarbon of the formula C 36 H 72 
 were to be isolated in a state of perfect purity and in large quantity from 
 some natural product, it would be impossible to absolutely identify it 
 as a compound corresponding to any particular structural formula by 
 any combination of methods of investigation now known, or whose 
 future discovery appears probable. Such a hydrocarbon would not differ 
 by one one-hundredth of one per cent, in its hydrogen or its carbon 
 content from its adjoining homologues, while in chemical and physical 
 properties there would be no measurable differences between it and 
 1 An address delivered at the Second Decennial Celebration of Clark University, 
 Worcester, Mass., Sept. 16, 1909. 
 
 104 
 
ORGANIC AND BIOLOGICAL. 1050 
 
 thousands of its four million undiscovered structural isomers, which, ac- 
 cording to the calculations of Cayley, are theoretically possible. Indeed, 
 in the case of the discovery of such a high hydrocarbon by any process 
 other than one of simple synthesis, no proof could be contrived which 
 would show that the substance might not well be a mixture of many iso- 
 mers and neighboring homologues; for all finite methods of purification 
 by fractional separation based on differences in properties must inevita- 
 bly fail when the numerical odds against them are so great, and we have 
 no choice in such a case but to resign ourselves with the best grace pos- 
 sible to an inevitably partial solution of our problem. 
 
 But without having ascended to such an altitude in the homologous 
 scale as in the instance just cited, it is often necessary or expedient to 
 accept incomplete answers in qualitative inquiries because of our thraldom 
 to the rule that unknown compounds in mixtures cannot in general be 
 fully identified without previous isolation in a state of purity. It is for 
 this reason that it is so common a practice in technical analysis to ex- 
 press the quantitative composition of familiar and important products 
 in conventional or collective terms. L/ong and thoroughly as the animal 
 fats have been studied, for example, there is probably no instance on 
 record of a quantitative examination of any natural fat in which it could 
 be safely claimed that the structural identity of all its fatty acids contain- 
 ing less than eighteen carbon atoms had been irrefutably established. 
 Nor would it be surprising under the circumstances if such a result were 
 never accomplished. 
 
 Thus handicapped, systematic qualitative organic analysis has de- 
 veloped slowly when compared with the simpler qualitative analysis of 
 the inorganic elements and salts. Yet, if we contrast the difficulties to 
 be overcome in constructing an orderly scheme for the separation and 
 identification of the list of less than one hundred elements with the diffi- 
 culties to be met in any corresponding scheme for the organic compounds, 
 and then recall what has already been accomplished in overcoming them, 
 and also the imperfections which present-day inorganic qualitative 
 schemes still exhibit when the rarer elements are included, the organic 
 chemist will find little cause for pessimism. The greater part of the con- 
 tributions to organic qualitative analysis have been made, however, with- 
 out much thought of the part which they might be made to play in 
 any comprehensive scheme of procedure, and have often owed their 
 origin to incidental observations made during the execution of investiga- 
 tions of broader scope and different purpose. Fischer's numerous char- 
 acterizations of compounds in the sugar, purine and protein groups, by 
 well chosen reactions and derivatives, and his ingenious separations 
 for the amino acids formed in proteolysis are illustrations of this fact. 
 Among the rather numerous handbooks of organic analysis, although 
 
 105 
 
1 05 1 SYSTEMATIC QUALITATIVE ORGANIC ANALYSIS. 
 
 many devote much space to qualitative testing, the speaker recalls only 
 one whose author (Barfoed, 1878) has been sufficiently venturesome to 
 incorporate the phrase "Organic Qualitative Analysis" in its title. Of 
 the many commendable partial schemes for the isolation and identifica- 
 tion, or the detection in certain classes of mixtures, of carbon compounds 
 belonging to restricted groups, we owe the origin of a large proportion 
 to an acute need of special analytical assistance in some department of 
 industry, research, or governmental control. To such cause we owe 
 much of what is most valuable in Allen's " Commercial Organic Analysis," 
 Post's " Chemisch-technische Analyse," and the works of Vortmann, 
 Dragendorff, Hoppe-Seyler, Konig, Leach, Sherman, and others. The 
 investigation of methods for the detection and determination of constit- 
 uent radicals has also proved a fruitful source of valuable material, much 
 of which has been made accessible for ready reference in H. Meyer's 
 "Analyse und Konstitutionermittelung organischer Verbindungen. " 
 
 The resolution of mixtures is usually the first, and often the most 
 difficult part of a qualitative analysis. Definite plans for correlation 
 in a broad general procedure of the methods of separation that have 
 proved effective in the study of restricted classes of mixtures have yet 
 to be proposed. The speaker is not in accord with the rather prevalent 
 view that it is useless to strive for broader and more systematic separa- 
 tion procedures. But, on the other hand, as he is unprepared to play 
 the prophet's role, it may be more profitable for him to confine the fol- 
 lowing discussion to the topic of systematic procedures for the identifica- 
 tion of pure compounds, this being an important division of the qualita- 
 tive problem whose solution seems nearer accomplishment. 
 
 Prior to 1831, the date of the inauguration of those revolutionary 
 improvements in organic combustion methods by Liebig, which rendered 
 it possible to determine the percentage composition of any carbon com- 
 pound with considerable accuracy and comparative convenience, it does 
 not appear that any comprehensive systematic methods for identifying 
 previously described organic compounds had been formulated, or that 
 the lack of them had been felt as a serious inconvenience. The num- 
 ber of pure compounds that had been described was comparatively small, 
 the possibility of laboratory syntheses for organic compounds having 
 only just become recognized, and the descriptions of such compounds 
 as were known were not scattered as to-day through an almost endless 
 list of special journals and treatises. A chemist of this earlier period, 
 if a man of extended practical experience, well read, and having access 
 to a good library, rested more or less content in the knowledge that he 
 could probably accomplish by a purely eclectic procedure, based on his 
 miscellaneous sources of information, ingenuity, and common sense, 
 all that was then analytically possible. 
 
 1 06 
 
ORGANIC AND BIOLOGICAL. 1052 
 
 Thanks to Liebig's writings and the influence of the students who passed 
 from his Giessen laboratory, his simplified methods of ultimate analysis 
 were not long in becoming widely known. In scientific laboratories 
 they were everywhere welcomed and adopted. This welcome was richly 
 deserved; for, besides serving as a means to determine percentage com- 
 position values which will perhaps always remain the most funda- 
 mental of chemical constants their use, in connection with the later 
 widely adopted vapor density molecular weight determination meth- 
 ods, furnished all information required for the calculation of empirical 
 formulas. These, if we add knowledge of genetic relations and chemical 
 behavior, become structural formulas with all the added information 
 as to chemical characteristics and individuality which are inherent in 
 the latter. The vapor density molecular weight determination methods 
 reached their climax for the organic chemist in the air displacement 
 form proposed by Victor Meyer in 1878. The prestige of the empirical 
 formula as an aid in compound identification was soon still further en- 
 hanced by the discovery of Raoult's principle, followed by the invention 
 of the Beckmann thermometer in 1888, these aids to molecular weight 
 determination finally enabling the inclusion among the compounds of di- 
 rectly determined empirical formulas of a large share of the non-volatile 
 compounds. Other causes about to be mentioned also conspired to bring 
 the analytical importance of the empirical formula to extreme promi- 
 nence. 
 
 During the two decades closing in 1880, the unprecedented increase in 
 newly described organic compounds had already begun to assume 
 the dimensions of a threatening deluge. The synthesis responsible 
 for the creation of a new species, being aware of its genetic relations, 
 and having determined its empirical formula, was usually in a position 
 to correctly interpret the chemical identity of his progeny; though 
 to prove that his discovery was really an original one by a search 
 through the swollen literature had become a task to be undertaken with 
 fear and trembling. The time rapidly approached when the healthy 
 future development of organic research seemed likely to receive a serious 
 check from the confusion and discouragement in store for investigators 
 who could only hope to escape plagiarism in recounting their alleged dis- 
 coveries by well-nigh interminable bibliographical delvings. Those of us 
 in the younger generation of organic chemists are not in a position to even 
 faintly appreciate the sigh of relief that must have been breathed by 
 hundreds of workers in many lands when these chaotic conditions were 
 ameliorated in 1882 by the completion of the first edition of Friedrick 
 Beilstein's great handbook of organic chemistry. With rare foresight 
 Beilstein had in season anticipated the mission which this remarkable 
 work had to fulfil, and its publication after twenty years of incessant 
 
1053 SYSTEMATIC QUALITATIVE ORGANIC ANALYSIS. 
 
 labor, occurring as it did at this critical period in the development of 
 organic chemistry, is of epoch-making importance to organic qualitative 
 analysis as well as to all other departments of the science. 
 
 Beilstein's "Handbuch" was a digest of the complete literature of the 
 modes of formations, properties and reactions of all the analyzed com- 
 pounds of carbon. It did not purport to be an analytical guide, and in 
 its introduction the possibility of a qualitative organic analysis at all 
 comparable to the inorganic is categorically denied. Nevertheless, 
 because of the completeness and orderly arrangement of its concise de- 
 scriptions, its importance as an aid in the identification of organic com- 
 pounds may be fairly estimated as greater than that of all the special 
 analytical treatises which have ever been issued. Its general classifica- 
 tion for the compounds has sometimes been criticized as clumsy and 
 confusing, but the division of species according to chemical function, 
 saturation, and in homologous series, has, on the whole, served the in- 
 terests of the analyst well; and the invention of a simple device for loca- 
 ting in its pages the description of any desired compound of known em- 
 pirical formula, which has been more recently made available through 
 the ingenuity and cooperation of M. M. Richter, the manager of the 
 Prinz Dye Works in Carlsruhe, has now long served in case of compounds 
 of this class to greatly facilitate their identification. 
 
 Richter's "Tabellen der Kohlenstoff-Verbindungen" with its 20,000 
 brief references to the literature and properties of the analyzed organic 
 compounds was issued in 1884. The first volume of the second edition 
 appeared in 1900 under the altered title of "Lexikon der Kohlenstoff- 
 Verbindungen." In its present completed form this edition registers 
 more than one hundred thousand compounds of determined empirical 
 formulas, and gives direct access to the full description and literature of 
 each by citation of the proper volume and page number of Beilstein. 
 As a bibliographical index for compounds of known empirical formula it 
 is hard to imagine anything simpler or more complete than the Rich- 
 terian classification. The exact position of every possible compound 
 (if we exclude the arrangement of isomers with reference to one another) 
 is automatically fixed by its formula alone, and is as easily found, and 
 in much the same manner, as a word in a dictionary through a knowledge 
 of the relative positions of its letters in the alphabet. The completeness 
 of the tabulation is suggestively indicated by the author's remark that 
 his guiding thought during its preparation was " Das Unwesentliche, 
 d. h. die weniger bekannten Verbindungen, stets in erster L,inie und 
 vollstandig hervorzuheben. " On the other hand, its use as the basis 
 for a method of identification for unknown organic compounds is often 
 attended with serious or prohibitive difficulties. 
 
 It has been already pointed out that an absolute determination of 
 
 1 08 
 
ORGANIC AND BIOLOGICAL. 1054 
 
 species among the carbon compounds is theoretically impossible by any 
 combination of tests in the case of compounds of extremely high molec- 
 ular weight, and that the unavoidable errors of ultimate organic analysis 
 with such substances are large enough to prevent analysts from making 
 any selection between a large number of seemingly possible and equally 
 probable empirical formulas. This unfortunate circumstance prohibits 
 the use of the Richterian system in large and important fields where 
 quantitative investigation by other methods may be conducted with good 
 prospect of success. For example, the dyestuff tables of Schultz and 
 Julius describe a hundred distinct tetra-azo dyestuffs having molecular 
 weights above 500, and some of them exceeding 1000. These colors are 
 many of them important, their constitutions well established by syn- 
 thesis, and their identification through their physical and chemical 
 properties, or at least their approximate identification which is often 
 all that is required is not especially troublesome. The absurdity of 
 an attempt to identify an unknown color of this class through its em- 
 pirical formula which would usually involve the quantitative deter- 
 mination of at least six elements with an impossible degree of precision 
 is so patent from the mere mention of the stoichiometric conditions that 
 it may be hoped it has never been made by any rational being. 
 
 A second defect in the method of the empirical formula, which in the 
 ordinary laboratory curtails its actual application even more than the 
 absolute limitation just mentioned, is the fact that much special 
 manipulation, skill and apparatus are necessary to insure trustworthy 
 results in elementary organic analysis, and that so much time is always 
 consumed in the preliminary arrangements for a combustion and in its 
 conduct. In the larger organic laboratories where the combustion of 
 new synthetic products is an almost daily incident of the routine of 
 investigation, and the equipment of the combustion room is maintained 
 at all times in a state of perfect preparedness for emergency calls, so that 
 no time need ever be lost in the mobilization for an analysis, the organic 
 combustion is not formidable to the initiated. But under other circum- 
 stances and they are the prevalent ones chemists do not resort to 
 the method of the empirical formula except under rather strong com- 
 pulsion, and many identifications which ought to be made are not even 
 attempted. 
 
 In view of these defects and inconveniences, it is natural to inquire 
 whether there is hope of securing in the future any scientific substitute 
 for the method of the empirical formula. In the comprehensiveness 
 and simplicity of its classification of compounds, it must be admitted 
 that it will be vain to expect anything but loss from radical changes in 
 the Richterian arrangement; but, if we accept the logician's definition 
 of a scientific classification as "Nothing more than a system of division 
 
 109 
 
1055 SYSTEMATIC QUALITATIVE ORGANIC ANALYSIS. 
 
 carried out in such a way as to best serve a given purpose," and if our 
 purpose is convenience and effectiveness in general qualitative investiga- 
 tion, the possibility of other and more scientific classifications is not to 
 be denied; and it has seemed to the speaker that the discovery of such 
 methods of classification is at present one of the important and attractive 
 fields for organic chemical research. What the final outcome of this 
 quest will be if we have the right to speak of a final outcome in a prob- 
 lem which from its nature permits of only progressive partial solution 
 no one can as yet speak with full authority. Some of the general 
 considerations bearing on the subject may, however, be brought to your 
 attention. 
 
 Scientific classifications are chiefly concerned with relations of resem- 
 blance and contrast. To answer the question what points of resemblance 
 and contrast must be regarded, and in what order, if we are to make a 
 classification scientific, is to say that no basis of classification (" funda- 
 mentum dimsionsis") is per se better than any other. All depends on 
 the ultimate object. If the object of a classification is ready diagnosis 
 of natural objects, it is evident that the characteristics used as differentiae 
 for distinguishing between groups should permit of easy as well as cer- 
 tain determination; and it is also a good quality in such a division to 
 collect individuals in the lowest group for comparison which are on the 
 whole most alike. Methods of subdivision which aim at discovering 
 something without regard to whether the resemblances of adjacent 
 species are fundamental or accidental, like the classification of words in a 
 dictionary according to the accidental alphabetical sequence of their 
 letters, are called artificial systems. The Linnaean and Richterean 
 systems belong to this category. No comprehensive system of division in 
 natural science is free from many artificial features. But these are more 
 likely to be prominent in the early than in the later stages of the develop- 
 ment of a classification, the pioneer in such work having to first bridge 
 his rivers with such structural materials as lie nearest at hand. 
 
 To the observant mind the discovery of possible differentiae for the 
 classification of natural objects is an easy and fascinating pastime, though 
 to make a wise selection may often be quite the reverse. Thus we read 
 in the quaint diary of the botanist Linnaeus under the date of June 12, 
 1632, in his "Lapland Observations": "Close to the road hung the under 
 jaw of a horse, having six front teeth, much worn and blunted, two canines, 
 and at a distance from the latter twelve grinders, six on each side. If 
 I knew how many teeth and what peculiar form, as well as how many 
 udders, and where situated, each animal has, I should perhaps be able 
 to contrive a most natural methodical arrangement of quadrupeds." 
 As with Linnaeus' quadrupeds, so with organic compounds we find a 
 multitude of easily determined properties from which we may choose 
 
 no 
 
ORGANIC AND BIOLOGICAL. 1056 
 
 the differentiae for our classification, and by the exact coincidence of a 
 sufficient number of these characteristics of different orders with those 
 of an unknown compound, the identity of the latter may be proved. 
 Qualitative elementary composition, color, melting and boiling point, 
 specific gravity, odor, taste, solubility, refractive index, specific optical 
 rotation, electrical conductivity, absorption spectra, color reactions, 
 precipitations, and general chemical behavior especially simple chemical 
 reactions that throw light on the nature of dominant atomic groups and 
 structural peculiarities may all be thus used. 
 
 Regarding the chemical compound, or individual, as the species of a 
 chemical system, it appears most natural to group these species in such a 
 way as to make the next higher unit or genus contain species which are 
 most similar in general chemical behavior. This would, for example, 
 tend to make congeners of members of all homologous series containing 
 the aldehyde radical, provided we could find sufficiently reliable and 
 simple chemical tests for showing the presence of the CHO group. Re- 
 cent chemical literature abounds in suggestions for tests suitable for 
 generic differentiae, though much additional work will be required in 
 every instance to determine the real value and exact boundaries of the 
 genera that their employment would create, there being ever-present 
 danger that overconfidence in the constancy of behavior of a reagent 
 towards a given radical in different structural environments may lead 
 to false conclusions. Thus it is not safe to assume that under certain 
 specified conditions all ketones will form oximes; all acids and phenols 
 will dissolve in alkali; all esters will be saponified; or all unsaturated 
 compounds will add bromine. In first delimiting a genus such assump- 
 tions may be adopted, after preliminary experiments, as tentative 
 working hypotheses ; but the contents and existence of the genus must be 
 held to be strictly provisional and dependent on the positive outcome of 
 the proposed genetic reaction when applied to a larger number of its care- 
 fully selected species, and to its negative outcome when tried with numer- 
 ous members of all genera of higher numerical designation in the same 
 classificatory order. It will also be the duty of the classifier to indicate, 
 in a manner that will leave no doubt in the minds of readers, all descrip- 
 tions, or parts of descriptions, for which he is personally responsible; 
 for unless some means is given for distinguishing between data which he 
 has verified, and others which he has not, the authority is liable to be 
 more or less implicated in the mistakes of others for which he need have 
 assumed no responsibility, but which will now tend to vitiate the value 
 of his classification as a whole. 
 
 It would be premature at this time to present in all its minutiae any 
 plan for such a classification as has just been suggested in its outlines. 
 Details in illustration of the speaker's original conception and partial 
 
 in 
 
IO57 SYSTEMATIC QUALITATIVE ORGANIC ANALYSIS. 
 
 execution of such a plan are to be found in the already published first and 
 third volumes of his "Method for the Identification of Pure Organic Com- 
 pounds." All that is desired here is to lead to a discussion of the ad- 
 vantages in the plan for Chemistry; and if it is sound, to arouse interest 
 with a view to eventually bringing about a wider cooperation for 
 furthering its future development. The difficulties to be overcome are 
 considerable. Recorded descriptions of organic compounds, while fre- 
 quently very complete for a few properties like melting and boiling 
 points, are commonly equally deficient concerning others especially in 
 exact data showing the extent of the influence of slight variations in chem- 
 ical constitution on the results of the selected differential tests. The occa- 
 sion hence arises for an investigation or partial reexamination of a con- 
 siderable proportion of the species receiving locations. If one has the pure 
 compounds with which to experiment, the tests are easily made. But 
 as only a few thousand pure compounds can be procured through com- 
 mercial channels, and most of these require some purification, sucess 
 in the construction of a comprehensive diagnostic classification implies 
 assistance from private collections throughout the world; for to syn- 
 thesize any considerable part of the rarer species would overtax the 
 facilities of the largest and best equipped of laboratories. 
 
 To bring a majority of the carbon compounds referred to in Richter's 
 Lexikon into an essentially "natural" classification of the kind sug- 
 gested would, assuming the study of tests and revision of constants 
 to be thoroughly done, perhaps involve a labor as great as the trans- 
 formation of the "artificial" botanical classification of Linnaeus into 
 the modern "natural" system as it was left by de Candolle. An 
 undertaking of this magnitude and character might presumably in the 
 present century be accomplished with greater benefit to science under the 
 direction of some such organization as the committee entrusted with the 
 periodical revision of Beilstein's "Handbuch" and the Richter "Lexikon" 
 than under private auspices. 
 
 MASSACHUSETTS INSTITUTE OF TECHNOLOGY, 
 BOSTON, MASS. 
 
 112 
 
THE OUTLOOK FOR A BETTER CORRELATION OF SECONDARY 
 SCHOOL AND COLLEGE INSTRUCTION IN CHEMISTRY. 1 
 
 If the question "Should more credit be allowed by institutions of col- 
 lege grade for work in chemistry done by pupils in secondary schools?" 
 were asked of any considerable number of teachers in those schools it is 
 easy to believe that the majority would make an affirmative reply, and 
 that all would at least be inclined to add to the query the traditional 
 language of the examination paper, "If not, why not? Give reasons for 
 your answer." Inasmuch as the present conditions with respect to the 
 correlation of the work in the two grades of schools is admittedly unsatis- 
 factory, and since these conditions are essentially determined by deci- 
 sions on the part of the colleges, it is fitting that the situation should be 
 occasionally reviewed, with the purpose of finding out, on the one hand, 
 how far the present situation can be defended and, on the other hand, 
 of seeking means by which better results can be attained. Others have 
 dealt with this subject from various standpoints, and the statements 
 which follow are made less with the expectation that anything like a 
 final word will be said, than the hope that a contribution of the experi- 
 ences of the teachers in one more laboratory, and a few of the conclu- 
 sions which they have reached, may do something to aid in the compre- 
 hension of one of the most perplexing problems which confront the teacher 
 of elementary chemistry to-day. 
 
 The experiences here recorded have been gathered from the routine of 
 instruction in a technical school, and it may be considered doubtful by 
 some whether observations made in the laboratory of a technical school 
 in which the instruction in chemistry becomes a part of a "step up" 
 system of requirements (that is, one in which successful work in subjects 
 of later years is directly dependent upon a thorough grounding in earlier 
 subjects to a degree that does not obtain in the less rigid sequence of 
 studies in the college) should be taken as a basis for conclusions bearing 
 also upon college work; but, while such doubts may be justified in the 
 case of a limited number of institutions in which chemical instruction is 
 merely a part of a general college course, it is increasingly true that more 
 and more students from all colleges are seeking the technical schools to 
 complete some of the professional courses which they offer. In the case 
 of the university the technical school may well be a part of its own sys- 
 tem; in the case of the college it means that its reputation for efficiency 
 in teaching is to be unexpectedly tested by some other group of instruc- 
 tors, and it should be as much a matter of concern to them to see that 
 their students have an adequate preparation in the sciences as to see 
 that they are soundly taught in mathematics or the humanities. Many 
 of the colleges have much room for improvement in this respect. 
 
 Let us first look at the situation as it apparently exists at present in 
 some of our typical institutions as indicated by the following brief sum- 
 maries. The term "entrance requirement" is assumed to represent 
 the work of a year with the ordinary time allotment for chemistry in the 
 preparatory schools. The data have been obtained through direct cor- 
 respondence with representatives of the institutions mentioned. 
 
 1 Presented at the second decennial celebration of Clark University, Worcester, 
 Mass., September 17, 1909. 
 
1 . Yale College. Does not require chemistry for entrance. Students 
 may take an examination for advanced standing, but rarely do so. 
 
 2. Harvard College. Those who have passed the entrance requirement 
 take the same lecture as those who have had no chemistry, but they have 
 special laboratory work and more advanced instruction in a special divi- 
 sion. They are also allowed to take a first course in organic chemistry 
 in the freshman year. Admission of such students to work in qualita- 
 tive analysis has not proved successful. Those' who present more chem- 
 istry than the entrance requirement are individually considered, but are 
 rarely excused from college work on the basis of secondary school work. 
 
 3. Cornell University. The entrance requirement is nearly the same 
 as that of the College Entrance Examination Board, but the passing of 
 this examination does not secure credit for introductory inorganic chem- 
 istry in the university. The student may take an examination for ad- 
 vanced standing if he desires. 
 
 4. Columbia University. Those who pass the College Entrance Ex- 
 amination Board examination are admitted to a special course in lectures 
 in chemistry, including a somewhat advanced treatment of the subject. 
 
 5. Syracuse University. For one year of chemistry in a normal school 
 credit is given for elementary chemistry in college, provided the student 
 takes another course in chemistry and passes well. After one year of 
 chemistry in a secondary school, pupils are allowed to take the regular 
 examination in elementary chemistry, and if they pass, credit is given 
 for that course. If chemistry is accepted for admission the student is 
 admitted to second-year classes, but no credit is given for elementary 
 chemistry. 
 
 6. Washington and Lee University. Students from secondary schools 
 with the equivalent of Remsen's "Briefer Course" are admitted to a 
 course including physico-chemical topics and to qualitative analysis. 
 If they do well, they are excused from the former at Christmas, and con- 
 tinue with analytical chemistry; otherwise they continue the course in 
 inorganic chemistry through the year. A few students from selected 
 schools are admitted at once to qualitative analysis, but no college credit 
 is given. 
 
 7. Washington and Jefferson University. Students from a few selected 
 schools are given credit for the first year of chemistry in college, provided 
 they take a later course in chemistry and attain a high pass record. Others 
 are required to pass an examination before any credit is given. Chemis- 
 try is given in the sophomore year in this institution. 
 
 8. Wellesley College. An advanced course is provided for those stu- 
 dents who have had a year of chemistry. Smith's "College Chemistry" 
 is used, and a somewhat exacting line of experiments is required. Some 
 quantitative experiments, some volumetric analysis and some inorganic 
 preparations are included. 
 
 9. Chicago University. Students who have completed one year of 
 chemistry in an accredited school are admitted to special courses and 
 complete the work preparatory for qualitative analysis, or elementary 
 organic chemistry, in about two-thirds of the time required by beginners; 
 that is, they complete two majors in chemistry in place of three. The 
 work of these two majors is carefully adapted to utilize and clarify the 
 knowledge already gained. 
 
 114 
 
10. University of Michigan. For a year of chemistry at an accredited 
 school four hours of university credit are allowed (sixteen hours per 
 semester is full credit). These students are admitted to a course some- 
 what less elementary than that given to beginners. 
 
 11. University of Illinois. A full year of chemistry in a secondary 
 school is accepted in place of one semester in the university, provided no 
 more chemistry is taken (and provided chemistry is not offered for en- 
 trance). When the student continues in chemical subjects he is ad- 
 vised to take the regular course of lectures in chemistry, but spends less 
 time in the laboratory. 
 
 12. University of Wisconsin.-*- Credit is given for entrance chemistry 
 to the extent of one or two units out of fourteen. These students enter 
 the same classes as the others, but have a slightly different laboratory 
 course. In the course of two months they appear to be on about the 
 same footing as those taking the subject anew. 
 
 13. Lehigh University. Up to two years ago certain certificates were 
 accepted from secondary schools but the results were so unsatisfactory 
 that an examination has been substituted. Those who fail take elementary 
 chemistry; those who pass are admitted to a course in theoretical chemis- 
 try. 
 
 14. Sheffield Scientific School. If the student passes entrance chemis- 
 try, he is allowed to take an examination to pass off the elementary 
 course in the scientific school, and if successful he is admitted to quali- 
 tative analysis. Very few students are thus admitted. 
 
 15. Stevens Institute of Technology. Students pass an entrance ex- 
 amination like that of the College Entrance Examination Board, but the 
 instructor finds that he cannot make use of the earlier work, and all stu- 
 dents take a course in elementary chemistry. 
 
 16. Worcester Polytechnic Institute. Earlier attempts to examine upon 
 a limited portion of elementary chemistry with the purpose of definitely 
 eliminating this from the college course were not successful. Note- 
 books are now examined, and when these indicate a satisfactory course, 
 the students are placed in separate divisions and given a different labora- 
 tory course. They attend the same courses of lectures as the beginners. 
 
 17. Massachusetts Institute of Technology. Students who have satisfied 
 the entrance elective requirement are admitted to a special class during 
 the first term, and the lecture and class-room instruction, as well as the 
 work in the laboratory, are designed to take advantage of the work al- 
 ready completed by the student in the preparatory school. The effort is 
 made to introduce new lines of experimentation, as well as to reawaken 
 interest in earlier work by encouraging the student to interpret the phe- 
 nomena which he now studies in the light of his more extended expe- 
 rience, and with the aid of such additional concepts as have been introduced 
 into the lectures and recitations. The two divisions of the class are uni- 
 ted for the work of the second term. 
 
 Of these seventeen institutions one does not recognize chemistry for 
 entrance, two make no specific provision for students who have had 
 chemical instruction in the preparatory schools, three provide special 
 laboratory instruction, but give no definite college credit, six provide 
 special instruction in both lecture room and laboratory, but without 
 giving college credit, while two give some college credit on certificate, 
 
and four excuse students from elementary college courses after special 
 examination. 
 
 These institutions are sufficiently varied as to locality and type to 
 justify the assertion that they represent the present practise on the part 
 of thoughtful college teachers. That there is apparently much duplica- 
 tion of effort is at once evident, and that this must result in some loss of 
 time, energy and enthusiasm hardly requires argument. Why, then, 
 have we so long tolerated this apparent waste, and why do we not imme- 
 diately take steps to avoid it? The answer seems to me to be this: It 
 appears to be impossible to select any point in the chemical instruction 
 received by the members of a college entering class at which they have 
 such a sound understanding of the facts and principles already studied 
 that this knowledge may safely be accepted as a foundation for further 
 college instruction; or, if such a point may be selected, it lies so near to 
 the beginning of the college course as to make a definite excuse from this 
 small amount or work practically meaningless. There is, of course, a 
 small proportion of students to whom this statement is not applicable, 
 but it holds true to so large a proportion that it determines the character 
 of the instruction which is given to all students who have had any pre- 
 vious chemical instruction. The situation does not appear to be appre- 
 ciably better in institutions having a definite entrance requirement in 
 chemistry than in others. 
 
 Some of the reasons for this state of affairs we will try to consider 
 presently, but let us first look at the conditions as they confront the col- 
 lege teacher who has an earnest desire to enable his students to utilize 
 every advantage which they have gained, remembering, however, that in 
 these days it is not a question of individual but of class instruction, so 
 far as the main features of a course are concerned. The college teacher 
 or the teacher in a technical school will find among the members of a 
 single class students of each of the following types, with many varia- 
 tions : 
 
 Student A. An intelligent, reasonably thoughtful pupil from a school 
 where there are small classes, a well-arranged one-year course and a 
 judicious, helpful teacher. Such a student is a source of constant pleas- 
 ure, and much can be done for and with him. 
 
 Student B. The chemical enthusiast who, during a course of one or 
 two years' duration has been permitted, because of his enthusiasm, to 
 work extra hours or to assist his teacher. He has won high praise and 
 occasionally merits it, but too often the college teacher learns to dread 
 the expenditure of energy and tact which is necessary to retain the good 
 will of such a student while bringing him to realize that a more profound 
 knowledge than his own may be possible; yet, when the battle has been 
 won, perhaps half of these men make excellent students. 
 
 Student C. The student who has had two years of chemistry, in a 
 course of ordinary excellence, under average conditions as to equipment 
 and teaching. He feels, with some reason, that all this should count 
 for a great deal, and no argument will wholly displace this notion. He 
 works without interest, and generally badly, and is a heavy load to carry. 
 You ask, Why not transfer him to the work of the higher years? We 
 reply, Because experience has shown that he probably lacks adequate 
 preparation for it, and will fail in it. The only practicable alternative 
 lies in so arranging his laboratory practise that he shall have as large a 
 
 116 
 
measure of new work assigned him as it is possible to oversee without 
 disproportionate attention on the part of the instructors. 
 
 Student D. A student of moderate ability from an average school 
 with a year of experience. His credentials are clear, but he has perhaps 
 had little personal instruction and his knowledge is ill-arranged and 
 vague, as to both fact and principle. He has no confidence in himself, 
 and there is very little which is final in his preparatory work. His is 
 one of the most difficult cases to provide for at the start, but often turns 
 out well in the end. 
 
 Student E. A student who has spent a year, or more rarely two years, 
 under inadequate instruction, which has been worse than useless. An 
 entrance examination may exclude him, but under other systems he be- 
 comes a troublesome factor in the complex problem and it may require 
 some weeks to discover or be sure of his trouble. His place is with those 
 students who take up the study of chemistry as beginners and his exclu- 
 sion from the more advanced class is logical ; but a transfer to elementary 
 classes when these are provided is almost certain to breed discontent 
 in the individual, and often disarranges other work of the term which, 
 by that time, is well advanced. 
 
 But the confusion of interest does not end here! The types just re- 
 ferred to have been selected essentially along the lines of general efficiency 
 of instruction and length of courses. It must further be recalled that 
 even efficient teachers vary widely in their conceptions of the ground to 
 be covered, and the college receives students who, during a single year 
 of chemical instruction, have had the chief emphasis laid upon descrip- 
 tive chemistry; others where it has been laid chiefly on "theoretical 
 chemistry;" again others where the course is largely one of physics rather 
 than chemistry; and, finally, where considerable qualitative analysis 
 has been included even in this brief time. 
 
 The conditions appear, then, to be these, briefly stated: Experience 
 indicates that the pupils who have had even two years of instruction in 
 secondary schools are, in general, not in a condition to take up work in 
 chemistry which is more advanced than that of the first year in the col- 
 lege, and for students who have had but a single year there is at present 
 so little that can be regarded as common knowledge that the present 
 apparent duplication of work seems unavoidable. Regarding this dupli- 
 cation more will be said presently. 
 
 Let us next face the question, Why is it that secondary-school courses 
 have failed, and, as it seems to me, are likely to fail, to serve as substi- 
 tutes for any considerable amount of college instruction in chemistry? 
 The reasons are far from simple, and they need some analysis. We may 
 distinguish, I think, at once between certain factors which, since they are 
 inherent in the nature of our science or in the period in the pupil's life 
 in which the instruction is given, are common to all schools, and those 
 elements in the situation which are the outcome of varying fitness on the 
 part of the instructors. 
 
 Is it not true that chemistry itself presents some peculiar difficulties? 
 It is often said that "physics is taught better in the secondary schools 
 than chemistry." I am inclined to think that, as a general statement, 
 it is essentially true. But might not the full truth be better stated in 
 this form: "Physics is more effectively taught than chemistry in the 
 secondary schools because physics is an easier science to teach?" It 
 
 117 
 
is true that chemical phenomena are plentifully at hand, and that our 
 very life processes are dependent upon them; yet they are not recognized 
 as such and are essentially unfamiliar. The teacher of chemical science, 
 and the practitioner who seeks recognition for his achievements, are 
 alike forced to realize that the tools which he employs, the working con- 
 ditions which he establishes and the terms in which the results of his 
 labors are to be expressed are unusual and strange and, because of this, 
 more difficult of comprehension by his fellow-men. 
 
 The beginner in chemistry is at a similar disadvantage as compared 
 with the beginner in physics. In his work in physics the pupil handles, 
 for example, the balance, the mirror, the pendulum or the battery, and 
 he makes his measurements in units which are largely familiar to him; 
 and the phenomena which he observes are not foreign to his daily life. 
 On the other hand, the very test-tube and beaker to which the student 
 of chemistry is immediately introduced are unaccustomed objects, the 
 bottle of acid is still more so, and we often accentuate the situation by 
 asking him to don breast-plate and armor for his personal protection, 
 in the shape of aprons or rubber sleeves. While, on the other hand, the 
 concepts and laws of physics may not be properly alluded to as "easy," 
 yet it seems to me evident that they make less demands upon the intellect 
 and the imagination than the fundamental principles of chemistry, if 
 these principles are to mean more to the pupil than mere memorized 
 statements. 
 
 With the growth of the holes in the pupil's clothing the strangeness of 
 the beaker, test-tube and acid bottle lessens, to be sure, but he is coinci- 
 dently introduced to increasingly complicated phenomena; he is asked to 
 conceive of molecules, atoms, ions, even of electrons; he is asked to form 
 some notion of valence, to construct chemical equations, and to "state 
 all that they express" a thing which you and I with our greater wis- 
 dom and experience may well hesitate to attempt. He must master the 
 principles of stoichiometry, that branch of chemical science which seems 
 to baffle the human intellect to a degree that never ceases to amaze even 
 experienced teachers. It may even happen that his course includes 
 such concepts as those of chemical equilibrium, the mass law, or the phase 
 rule which, in their relation to the proper subject matter of a secondary- 
 school course, somehow remind one of the records of those early chemical 
 processes found in the first chapter of Genesis in which it is quite inci- 
 dentally stated that near the close of the fourth day the Lord created 
 "the stars also." It is easier to forgive the ancient recorder for his lack 
 of a due sense of proportion than to excuse the twentieth-century instruc- 
 tor. 
 
 Keeping in mind, then, the newness of the chemical processes and chem- 
 ical concepts, and the fact that the latter necessarily make considerable 
 demands upon immature imaginations, may we not fairly ask whether it 
 is actually reasonable to expect that a young boy or girl of fifteen to seven- 
 teen will gain a really clear insight into chemical science in one year; 
 such an insight as will serve as a safe foundation for a chemical super- 
 structure without further strengthening through review? I think I can 
 hear teachers answering warmly in the affirmative. But, again, do they 
 not have in mind the exceptional rather than the average pupil? It 
 seems to me that experience indicates that the most that it is wise to at- 
 tempt in the case of the large majority of pupils of the ages named is to 
 
 118 
 
broaden their horizon by teaching them to interpret common phenomena 
 in the terms of chemistry, and with the aid of only the simplest funda- 
 mental principles to help in the understanding of those terms, leaving 
 the meaning of the more abstract conceptions to be learned in a college 
 course, or by later and more mature reading if the pupil is not destined 
 for college, but has an inquiring mind. I believe that the disparity be- 
 tween the immaturity of mind of the pupil and the demands of the sub- 
 ject matter assumed to be taught has been far too much ignored. I 
 think this is the more true in these days when it seems evident that our edu- 
 cational system, through its multiplicity of subjects and the over-promi- 
 nence of the baneful influence of the examination paper, tends to remove 
 nearly all opportunity for concentrated or independent thought on the 
 part of the pupil, or of originality in methods of instruction on the part 
 ofthe teacher. 
 
 I believe, then, that even the competent teacher, with adequate equip- 
 ment and the usual time allotment must find great difficulty in teaching 
 chemistry to even the more receptive pupils at the secondary-school age 
 so thoroughly as to permit the college to substitute it for any considerable 
 part of the college course, at least under present conditions. For, let it 
 be said with all humility, we college teachers too often made a sad mess of 
 it even with the advantages as to maturity and environment, which we 
 presumably possess. 
 
 The statement is sometimes made by college teachers that they would 
 prefer to receive students without previous chemical experience, and the 
 question may be raised whether or not it would be better to abandon 
 entrance requirements in chemistry. I believe it is the opinion of the 
 majority of college teachers, especially of those who have given the prob- 
 lem the most careful thought, that this would be very unfortunate. I 
 should consider it so far at least two important reasons: first, because, 
 while formal excuse from a definite portion of the college work is not yet 
 generally practicable, the experience already acquired by the student 
 can be made very helpful if judiciously utilized, and second, because it 
 is mainly through increased cooperation between the schools and the 
 colleges in an effort to secure better working conditions for the teacher, 
 and the adoption of a rational course of instruction in the secondary 
 schools, which will take into account all of the pupils, rather than those 
 alone who propose to enter college, that we may hope to attain better 
 results. 
 
 It is noticeable in the statements quoted above regarding the present 
 practise in the various institutions, that the state colleges are apparently 
 giving a greater amount of definite credit for work in the secondary 
 school than the others. This is frankly stated by some of the college 
 teachers to be due to the closer organic connection of the state university 
 with the general school system, and is admittedly done under slight 
 pressure. On the other hand, these institutions have, through the system 
 of school inspection on the part of the state universities, a more direct 
 means of influencing instruction in the preparatory schools. The outlook 
 for better conditions in the future is generally regarded as favorable. 
 
 Perhaps we may ask just here, What would these better conditions be 
 like? It is probably fair to say that they would be such as to avoid 
 duplication of work. Obviously repetition and duplication should be 
 reduced to a minimum, and no one would welcome changes which tend 
 
 119 
 
8 
 
 to bring this about more than I. But I think it is possibly true that 
 there is less actual duplication of work than is commonly supposed in 
 those institutions in which the students who have had a year or more of 
 chemical instruction are segregated in separate divisions. Let us take 
 a concrete case by way of illustration. The pupil in the secondary school 
 prepares chlorine, using salt, sulphuric acid and manganese dioxide, or 
 hydrochloric acid and manganese dioxide. The time available rarely 
 permits the use of any other method, and the chemical changes involved 
 are sufficiently complex to present some little difficulty for their complete 
 comprehension. Few pupils, as experience shows, really understand 
 that this is a typical, and not an isolated or unique procedure, and the 
 rdle played by the manganese dioxide is but vaguely grasped. It is 
 true that such students are asked to again prepare chlorine from these 
 materials in the college laboratory, but they are at the same time required 
 to study the action upon hydrochloric acid of such agents as lead dioxide, 
 barium dioxide, hydrogen dioxide, potassium permanganate or potassium 
 dichromate, and to discuss the changes involved from the common point 
 of view of the oxidation of the acid, and the proportion of actual duplica- 
 tion of work is really small. Similarly, in the study of the action of acids 
 upon metals, while it is desirable to ask the student for the sake of com- 
 pleteness to repeat the familiar process for the preparation of hydrogen 
 from zinc and sulphuric acid, this becomes a mere incident in the series 
 of experiments and in the broader discussion of all phenomena observed 
 which may well go so far as to include the principles of solution tension, 
 in the case of such students. 
 
 It is, apparently, work of this general character which many college 
 teachers are offering to those who have had earlier chemical training. 
 The laboratory work is, as we have seen, frequently accompanied by 
 lecture demonstration and recitations of a corresponding grade, and while 
 it does not, of course, appeal to the student as a step in advance, as would 
 some other procedure which seemed to give a stamp of finality to his 
 earlier studies, it may well be questioned whether it does not better foster 
 his intellectual welfare than the more alluring plan could do. It should, 
 however, be the purpose of the college teacher to keep closely in touch 
 with the actual and probably increasing average attainments of the pupils 
 sent to him, in order that he may take all proper advantage of the instruc- 
 tion already given, and it is probably true that a larger number of insti- 
 tutions should offer such moderately advanced courses than is at present 
 the case. 
 
 I propose next to refer briefly to one or two specific points at which it 
 appears to me that the instruction in the secondary schools might be 
 improved. I do this with much hesitation, for I realize that those very 
 details or methods which perhaps fail to appeal to me may well be very 
 dear to another, and I realize that I should be loath indeed to have the 
 actual efficiency of my own instruction judged by certain alleged quota- 
 tions on the part of some of my students, or even by the subsequent acts 
 of many of them. A conspicuous instance of the failure of some of our 
 hopes was afforded by a statement made by one of our students in a recent 
 written test that "nitroglycerine is used as a lubricant." 
 
 A question which many find difficult to answer is this: How far, 
 taking into account existing and not idealized conditions, is it just to re- 
 gard note-books as an index of the efficiency of the instruction as given 
 
 120 
 
in a particular school, or college? I shall not be rash enough to under- 
 take to answer this beyond expressing a conviction that while a note- 
 book which is well kept and carefully corrected probably indicates care- 
 ful, efficient teaching, a relatively poor note-book may represent more 
 accurately an overburdened condition of the teacher, which prevents 
 adequate inspection and correction, than actual inefficiency in instruc- 
 tion. For it is often true that much of apparent error in the records 
 may have been actually corrected in conference or class-room. This 
 does not, however, apply to some of the atrociously bad specimens 
 which are occasionally met with, nor, on the other hand, does it ignore 
 those note-books which are obviously not records of work done, but stud- 
 iedly prepared exhibits, executed through connivance of teacher and 
 pupil at the expense of a fundamental principle of all scientific work, 
 rigid honesty. 
 
 Is it not true that too many teachers are contented to have their stu- 
 dents perform more or less perfunctorily the magic "forty experiments" 
 which are said by some one else to represent a suitable course, rather than 
 to vitalize their instruction by devising ten, twenty-five, fifty-five or 
 any other number of experiments of their own to illustrate the facts or 
 principles which they themselves desire to fix in the pupils' minds, and 
 to see that these are actually discerned. The busy, often overburdened 
 teacher, will not always find time or energy to devise an entire course 
 of instruction, but the introduction of even a limited amount of well- 
 considered experiments or class-room instruction which represents the 
 personal equation of the individual teacher does much to maintain en- 
 thusiasm for the teaching which is often reflected in the work of the pupils 
 as well. 
 
 The deadening tendency of a mere following of a course of experiments 
 laid down by others shows itself also in a disposition to regard each ex- 
 periment as a thing apart, the nominal completion of which is a cause 
 mainly for relief, is also reflected in many instances in the notes sub- 
 mitted, which are long and minutely descriptive of really insignificant 
 details, but miss the real point of the experiment. This, in turn, comes 
 from the fact that the pupil is not sufficiently informed why he is asked 
 to perform the experiment at all, and in the strangeness of the work he 
 naturally confuses the important and the unimportant. For example, 
 he is often apparently left to think that a description of "the apparatus 
 used" is as essential when he pours silver nitrate solution from a bottle 
 into a test-tube containing a halide solution, as when he is preparing 
 nitric acid from saltpeter, and he elaborates his descriptions with the same 
 fidelity in the former ease as in the latter, with a very considerable aggregate 
 loss of good energy on his part and that of his instructor. But that is 
 not the worst of it, for he gains an idea that all experiments are to be 
 treated with similar uniformity in other respects, even including his 
 search for their hidden meanings. I do not, of course, advocate telling 
 the student what is to happen and then asking him to say that it did oc- 
 cur, adding, possibly, the color of a precipitate; but I do believe that a 
 great deal would be gained if nearly all experiments, or groups of experi- 
 ments, were more carefully prefaced in the laboratory directions by a 
 brief statement regarding the principles or the types of changes involved, 
 and if, then, the student were encouraged to make his observations with 
 reference to these statements and were required to show that he under- 
 
 121 
 
IO 
 
 stands how the given experiment actually confirms the points in ques- 
 tion. This would do much to avoid what is at present a wasteful expendi- 
 ture of time, muscular energy and eyesight all of which could be used 
 to increase the pupil's experience, and it would partially, at least, elim- 
 inate the vague groping which results as those appalling scientific mon- 
 strosities which follow the words "I conclude" in the note-book of many 
 a conscientious student. Have you ever recalled the bewilderment of 
 your student days, when you had no idea what to look at among so many 
 phenomena? Have you ever taken a half dozen experiments and can- 
 didly asked yourself what you can legitimately conclude from what has 
 been performed? It is very much like trying to answer some of one's 
 own well-sounding examination questions: a procedure which often causes 
 them to lose their attractiveness. 
 
 Do we not then, tend to lay too much stress upon mere performance 
 of experiments, and devote too much time to the making and reading 
 of descriptive notes which are often copies of the experiment manual, 
 and too little time to helping the pupil, through judicious suggestions 
 regarding the experiments and through questioning at the work-table 
 and in the recitation room, to comprehend what it is all about, and the 
 relation of a given experiment to others already performed? 
 
 In order that the perplexities of the college instructor may be brought 
 more clearly to mind, and in order to illustrate certain types of note- 
 books, I reproduce here a few pages from the books presented in connec- 
 tion with the entrance elective requirement of the Massachusetts Insti- 
 tute of Technology. The first (Fig. i) is a representative of a rather small 
 number of superior books. The observations are carefully recorded, the 
 deductions are valid and well expressed and there is evidence (not shown 
 in the cut) that the note-book had been inspected and corrected. Un- 
 der existing conditions as to numbers of pupils to be taught it is probably 
 too much to expect that all will attain a standard which this note-book 
 appears to represent. To all appearances the records are original and 
 the instruction efficient. 
 
 The pages reproduced in Figs. 2 and 3 are of a not uncommon type. 
 The first leaves one in doubt as to what part of the work has been per- 
 formed by the pupil, since the statements made regarding the physical 
 properties could have been copied from a book, the records of experi- 
 ments performed are distinctly wrong and, in the case of the alleged 
 preparation of chlorine, would, if ever followed, lead more directly to a 
 residence at a hospital than to any worthy scientific end. Fig. 3 shows 
 a page which makes no pretense of being anything more than a mere 
 record of a useless mixing of a few solutions, and moreover these records 
 are also entirely wrong. 
 
 The two pages just commented upon did not bear any evidence of in- 
 spection on the part of the teacher ; that shown in Fig. 4 bore the stamped 
 legend "approved," but a careful inspection leaves one in doubt as to 
 what particular feature of the record warranted this, unless it may be 
 the evidence of sympathy (?) on the part of the pupil with the tendency 
 towards spelling reform. 
 
 These are not exceptional pages; they are representatives of many 
 that pass under our inspection each year, and I ask you, with all sym- 
 pathy for the teachers concerned, what evidence does any but the first 
 give that one may safely omit a review of the ground supposed to be 
 
 122 
 
Fig. 1. 
 
 Fig. 2. 
 
Fig. 3. 
 
 Fig. 4. 
 
II 
 
 covered by this work in a college course which is primarily expected to 
 furnish a safe foundation on which there is afterwards to be erected a 
 very considerable superstructure of chemical knowledge? Are we not 
 justified in our perplexities? 
 
 I should like also to appeal to the teachers in the preparatory schools 
 to encourage the pupils to better economize their laboratory time. Too 
 many are allowed to placidly watch a crucible heat, or a solution boil, 
 when other experiments might be in progress at the same time, and these 
 habits are difficult to overcome. I should like to suggest, too, that some 
 of the most promising pupils are often seriously harmed by allowing them 
 to work too much by themselves, or by encouraging them to go beyond 
 their depth in a particular line in which they appear to be specially in- 
 terested, to the detriment of their fundamental work. Some pupils 
 usually come to college with an exaggerated sense of their own attain- 
 ments and it frequently requires long and tactful persuasion on the part 
 of the college instructor before they can be reduced to reasonable humility. 
 
 On the other hand, I venture to plead that all proper encouragement 
 be given to pupils to take advantage of such special privileges as the col- 
 leges offer. It is not an infrequent occurrence to find a pupil who tells 
 us that he has been advised by his teacher to take the elementary course 
 for beginners as one in which he will incur less risk of failure. Were 
 the examination the goal of the course, there obviously would be little 
 to criticize in this suggestion; its effect upon the student as an embryo 
 scientist is seldom happy. 
 
 In conclusion let us ask, how can we make the work in chemistry in 
 the various institutions more mutually helpful? 
 
 1. By a more extensive cooperation on the part of the colleges and 
 technical schools in the way of separate courses for those who have taken 
 chemistry before entrance, a closer study of the problem on the part of 
 all, and a readiness to recognize improved conditions. 
 
 2. By an intelligent delimitation of the secondary-school course, so 
 that it will only offer what the pupil can best assimilate at the age and in 
 the environment in which he works. This is too large a topic for dis- 
 cussion in this connection, and it is sadly complicated by the necessity 
 for furnishing a course which shall be alike useful for the pupil who ex- 
 pects to enjoy college opportunities and his less fortunate associate. I 
 plead, as I have often done, for a course which is fundamentally descrip- 
 tive in its character. I do not mean a mere catalogue of facts, but a course 
 in which selected facts are taught for some specific reason, which is in- 
 variably explained to the pupil, and in which these facts are interpreted 
 for him in terms of the simplest of the fundamental principles and con- 
 cepts, so often repeated and constantly utilized that they may ultimately 
 mean more than memorized paragraphs from what he may later remem- 
 ber only as "a book with a green cover." I think there can be no greater 
 mistake than to suppose that such a course is a less worthy one than such 
 as is often pointed to with pride as a "theoretical course," and no teacher 
 should consider that it will demand less than his best efforts, supplemented 
 by all his knowledge, to utilize the opportunities for helpful and thorough 
 instruction which such a course affords. It is, of course, difficult to de- 
 termine whether or by how much the instruction of the boy or girl destined 
 for college should be differentiated from that of their fellow-students, 
 but I venture to hope that a decision may yet be reached, through coflpera- 
 
 123 
 
12 
 
 tion, which may permit us to select a limited field which shall be so well 
 covered as not to necessitate repetition in college, and that this may be 
 done without prejudice to the candidate or non-candidate for college 
 credits. How soon this will come, or how large this field may be, I do 
 not venture to predict. 
 
 3. By increasing the time allotted to chemistry in the secondary schools 
 until it is more nearly commensurate with the dignity and difficulty of 
 the subject. Whether such increase should amount to one third, or 
 some larger fraction of the present time allotment is a point which those 
 actively concerned in the teaching can best determine. The increase in 
 time should be asked for mainly in the interests of those who will not pur- 
 sue the study of chemistry further, but it will also presumably hasten 
 the time when a definite point of articulation with the college work, as 
 just suggested, can be fixed. 
 
 Finally, there is the urgent need of decreasing the demands made upon 
 the teacher of chemistry in the secondary school for duties other than 
 those of chemical instruction, and also a critical need for relatively more 
 instructors. I believe that a very large proportion of the unsatisfactory 
 results now noticeable are due to the fact that in most of our schools it is 
 not humanly possible for the teaching force to accomplish what should be 
 expected of them, or to be at the desk of the pupil when he reasonably 
 needs assistance. In some schools which have come under my observa- 
 tion the distribution of supplies must be attended to by the senior (or 
 often the only) instructor, an operation which consumes a half hour or 
 more. 
 
 Probably no science demands for its understanding by the beginner 
 more individual instruction in laboratory and class-room than chemistry, 
 and the school authorities should realize this. When they do we shall 
 have much cause for rejoicing, and much of the present groping and be- 
 wilderment on the part of the young student will give place to enjoyment 
 in the study of a science which is really second to none in its attractive- 
 ness or value when pursued under favorable conditions. 
 
 It is a pleasure, in closing, to say that I feel that too much praise can 
 hardly be given to the loyal, hard-working, intelligent and inspiring 
 teachers who are accomplishing so much in behalf of our science in the 
 training of the beginners. No thoughtful college teacher can fail to 
 recognize the good work done in very many schools throughout the coun- 
 try, and while many feel that more definite recognition in the college 
 curriculum can not wisely be given to this work at the present time, I 
 am sure from the messages which have recently come to me from many 
 colleagues in many institutions that there is an increasing appreciation 
 of the fact that the way to better things lies through a sympathetic ap- 
 preciation and study of our common problem and our common difficul- 
 ties. 1 
 
 1 In a discussion which followed the presentation of this and other papers on 
 educational topics, a statement was made by a secondary school teacher of recognized 
 standing to the effect that many such teachers had become indifferent to the opinions 
 of college instructors, since it is "impossible to satisfy them any way." While I 
 heartily sympathize with the thoughtful teacher who desires to teach his subject in 
 his own way and with his own ideals in view, and deplore any attitude of the colleges, 
 collectively or individually, which tends to interfere with this, it seems to me that the 
 common cause of greater total efficiency in instruction can hardly be served by ignoring 
 
 124 
 
13 
 i 
 
 If there can be a determination, on the one hand, to undertake only 
 so much as can be well taught and to give the largest practicable vitality 
 to the instruction, and, on the other hand, a disposition to promptly 
 recognize and utilize every bit of ground gained which offers a secure 
 foundation for later work, a more satisfactory situation than that which 
 exists at present can hardly fail to result, even though the degree of 
 recognition of secondary school instruction may fall short of that which 
 some desire. H. P. TALBOT. 
 
 MASSACHUSETTS INSTITUTE 
 OF TECHNOLOGY. 
 
 HIGH SCHOOL CHEMISTRY: THE CONTENT OF THE COURSE. 1 
 
 Every teacher in the high school of to-day finds himself in stimulating 
 circumstances. He is obliged to question himself closely as to the part 
 that his subject plays in the curriculum, for, at least in the large cities, 
 the long-discussed change in the character of the high school is upon us. 
 The reason for the change is found in a realization of the facts that in the 
 past, high school education has been enormously wasteful; that eighty 
 to ninety per cent, of our pupils do not complete the course; that only a 
 small part of the remaining per cent, achieve the purpose for 
 which the whole course has been framed, that of entering college. 
 The evidence that the change has actually begun is found in the estab- 
 lishment of trade and vocational schools, in the frequent discussion of 
 questions pertinent to these points, and in the statements of principals 
 and superintendents that something must be done to stop the enormous 
 educational waste; and in their declaration that the high school must 
 meet real needs, must give the boy or girl the education that is best for 
 him or her, as a member of the human group, with little reference to col- 
 lege entrance. 
 
 Among the changes that are coming from a recognition of these facts, 
 we find the importance of science in the high school largely increased. 
 The fact that it is science that has produced the great material advance 
 of the past century makes it certain that in the further turning from formal 
 to practical education, science will play a larger part. It is the purpose 
 of this paper to inquire into the manner in which these changing condi- 
 tions are reacting on the high school course in chemistry, and to discuss 
 some of the considerations that are determining, or should determine, 
 a new course of study. The speaker wishes also to discuss, in general, 
 the problem of high school chemistry, presenting personal and perhaps 
 even extreme points of view. 
 
 We may classify the various forces that are shaping the new course as 
 external and internal. In the first class we find: (a) a lessening of the 
 college influence, due to a realization of the necessity of educating for 
 other purposes than college entrance; (6) a tendency to put chemistry 
 
 the opinions of the colleges, even if they are mistaken. May it not be true that the 
 secondary school teachers lack some courage, or at least some persistence, in forcing 
 their convictions upon the college teacher? They have the privilege of speaking from 
 a fullness of experience with the young pupil which the college instructor usually lacks. 
 1 Presented at the second decennial celebration of Clark University, Worcester, 
 Mass., September 16, 1909. 
 
 125 
 
14 
 
 earlier in the course and to give a second year of it; (c) what we may call 
 the lay demand for practical education. 
 
 The lessened college influence will give to the body of secondary teach- 
 ers not only greater freedom in the selection and arrangement of their 
 material, but what is of even more importance, because it serves as a 
 stimulus to their creative ability, a realization of the importance of their 
 own great work and their responsibility for it. The lack of this kind of 
 freedom is in part responsible for the condition that exists to-day when 
 the high school, paying comparatively high salaries, can not get enough 
 good men, while the college apparently has more than it needs at a smaller 
 compensation. This is not the least of the evils that have resulted from 
 the college domination of the high school. Others have often been 
 pointed out and are well known. The course of study can never be adapted 
 to the real needs of the high school so long as it is framed by the college, 
 at the best a force operating at a distance, at the worst a power acting 
 for needs it cannot know. The college, as far as the high school was con- 
 cerned, always had the idea of preparation, not growth, in mind. A 
 thousand boys went through a course in chemistry whose nature was 
 determined solely by the needs of the three or four who were to be trained 
 to be expert chemists. It is often said at this point that the course which 
 best prepares the pupil for advanced work is also best for every other 
 boy. It is nearer the truth to say that the education which best meets 
 the needs of the growing member of the human whole ought to be the 
 best preparation for college. 
 
 Chemistry earlier in the course and perhaps a second year of it; the first 
 of these conditions may bring dismay to many teachers; the second, 
 delight to all, surely. Certainly some changes in the traditional course 
 are necessary in teaching chemistry in the second year. On this point 
 the speaker can refer to an experience covering nearly seven years. During 
 all that time chemistry has been taught to some second-year students. 
 At times fourth-year students and second-year students have been taking 
 nearly the same course simultaneously in separate classes; at other times 
 the two terms of students have been mixed in the same class. In both 
 cases a certain degree of success with the second-year students has been 
 obtained, even if we judge by no other standards than results of college 
 entrance and state board examinations. Speaking for the moment from 
 the standpoint of the college entrance syllabus, but little change is neces- 
 sary to adapt the chemistry to second-year students. A less rigorous 
 insistence on the philosophical development of the atomic and other 
 hypothesis seems to be the most necessary item of change. In any case, 
 as far as the ability of the student to comprehend is concerned, the differ- 
 ence between individuals is much greater than the difference between 
 second- and fourth-year classes. The general average of work is consid- 
 erably better in fourth-year classes, but this is explained largely by the 
 dropping out of weak material. 
 
 To meet the demand for practical education, we find that there is a 
 decided tendency to introduce into the high school a great deal more of 
 chemical technology than there was in the older course. There are some 
 who go so far as to say that the high school ought to give the pupil a means 
 of earning his living; that chemistry should be taught so as to fit him for 
 some direct employment in practical occupations. While admitting 
 this as a possible ideal, the view implies such an extreme change in the 
 
 126 
 
15 
 
 character of the high school that it is not advisable to take it into con- 
 sideration in the present discussion, except to admit that, given time, it 
 would be possible to accomplish this result. Along with the demand 
 for technical education, we find a tendency to fill the course with a great 
 deal of matter that is associated with the home and every-day life. These 
 two demands have come largely from without. They have done great 
 good and have added much to the human interest of our science. We 
 teachers are very prone to an academic point of view, and the stimulus 
 has been a needed one. Yet with the good, there is some danger. There 
 is a tendency in some quarters to emphasize the technological details 
 of processes, to fill the discussion with technical terms, so that the pupils' 
 talk bristles with tuyeres and downcomers and the particular names of 
 the many towers that find application in manufacturing chemistry. 
 The chief evil of this kind of instruction is that it produces rather showy 
 results, it seems to indicate more knowledge than really exists. More- 
 over, a technical process of to-day is a very complicated thing. It is 
 improved every year and we find to our discomfiture, on visiting the 
 factory, that the process we have so carefully learned from the text- 
 book differs in a hundred details from that actually employed. 
 
 The chemical interpretation of the ordinary phenomena of the house- 
 hold is a very interesting matter. Unfortunately many of these inter- 
 pretations are very complex, others are unknown. Some are simple 
 enough to be comprehended by a beginner, and certain food tests and 
 the like can be taught so that the pupil can go through them in a more 
 or less mechanical fashion. But surely these do not constitute a suita- 
 ble vehicle for the transmission of that highly organized mass of knowl- 
 edge and way of thinking which we know as chemistry. The intellec- 
 tual and material advance that our science has brought to the world has 
 not come from the knowledge of isolated test-tube reactions, but from 
 the brilliant imaginings of the authors of its great hypotheses, from the 
 realizations of its tremendous generalizations, from the perceptions of 
 most deeply hidden relationships among the things that we call matter. 
 If this that we teach our pupils is to bear the name of chemistry, it must 
 give them at least a glimpse of these deeper things. Technological chem- 
 istry and household chemistry have a very proper place in the high school 
 course, but they should never be over-emphasized. They afford the 
 illustrative material which the good teacher will constantly use to give 
 interest to his work by showing what good the science has brought to 
 mankind. But a course composed almost wholly of such material, as 
 has been proposed, would not be chemistry, and it would probably not 
 be science. There would be an absence of principles of relationships. 
 A pupil might indeed learn that there exists a simple process for the 
 manufacture of soda, but he would not share in any degree the kind of 
 thinking that has made this and a thousand other processes possible. 
 I hold that it is our chief duty to give him this kind of knowledge. 
 
 Coming then to the internal considerations which shall help shape our 
 new course of study, we must inquire what high school chemistry should 
 seek to accomplish for the pupil. One way of answering this question is 
 by asking ourselves what it has done for us as individuals. We know 
 that it has made us broader men and freer human beings, and it is fitting 
 that we should seek to have our pupils attain in some degree this high 
 end. Again, it is certain that one who has been through a good course 
 
 127 
 
i6 
 
 in chemistry, who has learned the principles of chemical action, and com- 
 prehended the great laws that the science has revealed, looks upon the 
 world about him in an altogether new way, so much so that with the 
 increase in the general knowledge of science there is being produced a 
 new type of world mind. Our pupils must be taught so that they shall 
 share in this new world mind. 
 
 THE LABORATORY ASPECT OF THE COURSE. 
 
 The course will continue to be based on experiment, the amount of 
 laboratory work being limited only by the physical possibilities of the 
 situation. The experiment will precede the class discussion in order 
 that the pupil may conceive the things that he is talking about as reali- 
 ties. Chemical thinking cannot go far without these definite concep- 
 tions. It requires images of real things, and it is this point of view that 
 should determine the character of our laboratory work. There seems 
 to be considerable difference of opinion, if not confusion, on this point. 
 
 There is the point of view which assumes that it is the purpose of the 
 experiment to prove the statement of the teacher or the text. Because 
 there was so much that was bad in reliance upon authority in older types 
 of education, it is felt that science must have none of this, but must ac- 
 company everything by rigorous proof. Following this method at its 
 worst, the pupil is stimulated into a condition of perpetual doubt. He 
 meets every statement with a but, and has rather the air of believing 
 that some scientific charlatanry is being imposed on him. This is wrong; 
 science does not have this attitude of perpetual doubt. It requires the 
 most rigorous proof from discoverers of new things, but if each of us 
 had demanded ocular demonstration at each step in our advancing knowl- 
 edge, we should probably still be somewhere in the realm of descriptive 
 inorganic chemistry. Moreover, it is a serious scientific mistake to let 
 the pupil think that a single experiment performed under the ordinary 
 condition of the beginner's laboratory proves much of anything. If it 
 does, the speaker has seen many curious things proved in his time. Let 
 us be frank: these experiments show at best the line of thought by which 
 the proof is obtained. They illustrate the proof they do not give it. 
 
 Nor does the theory that the pupil should, in the laboratory, rediscover 
 the fundamental truths of the science, give us a right basis for experi- 
 mental work. Followed to the extreme, this method soon reduces itself 
 to an absurdity. Take, for example, the experiments of Lavoisier, which 
 afford such an excellent starting point in the teaching of the subject. 
 The pupil is given some metals and a balance, and is supposed, in an hour 
 and a half, to rediscover what it took the best minds the world then pos- 
 sessed several centuries to accomplish. The fact the pupil's laboratory 
 record, duly attested by the teacher, indicates that he independently 
 accomplished this prodigious feat is a comment on the system. All that 
 is done in this method at its best, is the arousing of the pupil's curiosity, 
 which is later gratified by judicious^ suggestions at the proper moment 
 from the teacher. There is no rediscovery; the line of thought has sim- 
 ply been retraced, and the big steps have ever been taken by the teacher. 
 To be a discoverer you must be the author of your own curiosity. An- 
 other trouble with this method is that once committed to it the teacher 
 is driven to curious round-about expedients to prevent the pupil's hav- 
 ing knowledge in advance of the thing he is going to see. l A here are 
 
 128 
 
17 
 
 hundreds of instances where the pupil should have this knowedge in ad- 
 vance. 
 
 The speaker is more and more convinced that while the laboratory 
 should to a certain extent seek to accomplish the things which the hold- 
 ers of two points of view consider desirable, its real purpose is to afford 
 illustrative material, and by illustrative material he means that which 
 will give concrete ideas images of things and processes. One might 
 read hundreds of pages about chlorine, but if he had never seen it he 
 would never know it. This is the great work of the laboratory method, 
 to teach things and not literal symbols for them. We should seek this 
 end, and let other considerations give way to it. 
 
 And we shall not neglect to exercise the pupil's scientific imagination. 
 Chemical thinking requires this faculty. After he has been well grounded 
 in the method of the laboratory, we shall want the pupil to learn to fore- 
 see chemical possibilities. The progress of the science has been by the 
 working together of experiment and imagination, the one reacting upon 
 the other and each suggesting in turn new steps in the advancing knowl- 
 edge. 
 
 THE CLASS-ROOM ASPECT OF THE COURSE. 
 
 It is no longer being framed exclusively for the college entrance re- 
 quirement; our course will not require us to cover so much material as 
 it did formerly. Discussion of the rare elements and their compounds 
 will give way to a more intensive study of those that show typical chem- 
 ical actions, and establish the main lines of thought. We shall prefer to 
 do this by reference to the things of the practical life where we can, but 
 we will not go into the chemistry of foods, dyes, textiles and the like, 
 knowing that this matter is far too complex for us to use in establishing 
 the laws and relationships that are necessary for a comprehension of the 
 science. We shall draw from every aspect of chemistry in our effort 
 to establish the principles of chemical action. Our teaching may grow 
 less descriptive and more dynamic. We may find it better to study 
 types of chemical action than to study elements and compounds. As 
 suggestion along this line, we might proceed, after reaching the defini- 
 tions of chemical action, element and compound, to the general study of 
 simple decompositions, using many experimental illustrations. We would 
 bring in the ideas of stability and heat of formation. We would then 
 proceed to direct combinations, simple replacements, and so on, until 
 finally the pupil would have a very good idea of the comparatively few 
 types of chemical action. He would acquire incidentally a very prac- 
 tical descriptive knowledge. 
 
 Our course will necessarily continue to pay a large amount of atten- 
 tion to chemical theories, in order that we may have the means of seeing 
 analogies and interpreting results. The mechanism of chemical changes 
 is so far removed from direct observation by the senses that any attempt 
 to comprehend these must be largely by aid of the imagination. The 
 atomic theory has given us a splendid instrument for this purpose. We 
 should retain it even if it had done nothing more than give us a system of 
 chemical formulas, or made it possible to represent chemical actions by 
 equations. Only one who has attempted to teach chemistry without the 
 use of these symbols can fully appreciate what a tremendous aid they 
 are. We shall therefore want to establish the atomic theory rationally, 
 and to show how formulas are determined. This is perhaps the most 
 
 129 
 
i8 
 
 difficult part of our work, but the fact that many pupils fail utterly to 
 comprehend this matter is no ground for its omission from the course. 
 There are many who succeed, and we must not forget that those who fail 
 at least learn that such knowledge was acquired by human reasoning 
 and patient experimenting. We should make our pupils feel that these 
 theories are very practical things indeed, since it is largely by their aid 
 that the science has advanced and brought material benefits to mankind. 
 
 We have in the past been given to considerable drill in certain types of 
 chemical problems, largely because of the demands of college entrance 
 examinations. There has been a good deal of mental gymnastics in the 
 matter. These calculations should be taught in a less formal way; the 
 laboratory is the best place to do it. Let the pupil calculate from the 
 equations the quantities of substances he needs for his reaction, and 
 then actually mix them in these proportions. Let him get practise in 
 correcting gas volumes in the course of experiments involving simple 
 gas measurements. Knowledge acquired in this way has a far greater 
 staying quality than that obtained in formal class-room drill. 
 
 As we have already said, chemical technology will find a place in the 
 course, but it must be taught by principle too. In the Solvay process, 
 for example, it is more important that the pupil should get the idea of 
 precipitation by differences in solubility than that he should know the 
 mechanical details of the carbonating towers. It is more important 
 he should know that the process is only commercially profitable because 
 the ammonia is recovered, thus getting hold of the principle of the utiliza- 
 tion of by-products, than that he should know the factory terms for the 
 machinery and operations. A good course in manufacturing equip- 
 ment, in which different types of furnaces, towers and the like were 
 grouped and compared, might be of great practical and educational im- 
 portance. But isolated bits of such information have no such value. 
 
 Our high school chemistry might well include a treatment of more 
 organic compounds than it has in the past. This knowledge can readily 
 be acquired by reference to inorganic types. So many of the simpler 
 derivatives of the hydrocarbons are things of every-day life that in order 
 to include them we can afford to sacrifice some of the things of the tra- 
 ditional elementary course. The pupil needs, moreover, some intima- 
 tion of the character and extent of the organic branch of the science. 
 
 In conclusion, the speaker feels that the best hope for the improvement 
 of high school chemistry lies in discussions of the kind we are engaged in 
 this morning. The experimental end of our work has been so new and 
 interesting that much of our time has been spent on these matters. But 
 the time is at hand when a reconsideration of the course as a whole in 
 its general relations would be of benefit to the teaching of the elementary 
 science. JESSE E. WmTsiT. 
 
 DKWITT CLINTON HIGH SCHOOL, 
 NEW YORK CITY. 
 
 CHEMISTRY IN SECONDARY SCHOOLS. 1 
 
 It is not necessary in a gathering such as this to recount the stages in 
 the history of chemistry teaching in secondary schools how, from the 
 
 1 Presented at the second decennial celebration of Clark University, Worcester, 
 Mass., September 16, 1909. 
 
 130 
 
19 
 
 purely descriptive natural philosophy of the early college we finally as- 
 sayed the teaching of chemistry and physics as sciences; how the mis- 
 cellaneous encyclopedic instruction has been replaced by courses, de- 
 signed, in these latter days, to develop power for the pupil rather than 
 to impart knowledge. 
 
 The changes in content and method of formal secondary-school instruc- 
 tion have been brought about by the colleges; by advice, by supplying 
 the teachers and most drastically, by the requirements for admission. 
 While the bulk of the class might pass from the school and not be heard 
 from again, the failure of a pupil to pass the college examination is quickly 
 brought home to the teacher, so that the entrance examinations have 
 become the standard of the school. 
 
 During the last fifteen years four syllabuses have been published which 
 have decidedly affected the teaching of chemistry in schools; in 1894 
 that of the Committee of Ten, descriptive and general; in 1898 a Harvard 
 syllabus, largely quantitative and scientific in method; in 1900, the 
 syllabus of the College Entrance Examination Board, a plan for a course 
 I hesitate to classify; in 1905, the last revision of the syllabus of the New 
 York Department of Education, a historico-systematic course. 
 
 There is almost nothing in common to these four courses, and although 
 the College Entrance Examination Board maintains and strengthens its 
 hold upon the schools it has never, fortunately for the pupils, conducted 
 its chemistry examination in accordance with its syllabus. 
 
 If we examine the texts to find what is being taught in high schools 
 we find the chemistry text-books to be descriptive or theoretical; very few 
 have successfully combined the two. The descriptive texts usually 
 become encyclopedic, try to include all the elements, strange compounds, 
 the latest processes and weird discoveries, often curtailing or entirely 
 displacing those common things we are too liable to take for granted 
 that every one knows. The theoretic texts are largely the product of 
 college men. These tend to become too abstract and sacrifice the 
 pupil to the subject. One elementary text of very wide use devotes 
 two pages to a discussion of the action of bleaching powder, but does not 
 state how it is used or for what goods. 
 
 If a subject is to be treated as a science many facts must be given 
 and understood in order that the pupil may acquire a comprehensive 
 idea of the subject. It is folly to expect thorough understanding of a 
 part without a general knowledge of the whole. The high schools can- 
 not train chemists or engineers. Time and cost do not admit of such 
 intensive science teaching, even if it is desirable. Such teaching should 
 be left to the college. 
 
 If we take the pupils as we find them in our large city high schools 
 they are not well informed and have little opportunity to be. They 
 live in a complex environment. The city boy or girl is brought in con- 
 tact with but few simple phenomena; a push of a button a bell is rung; 
 another push a door is unlocked; another push a light appears. The 
 modern apartment is a complicated structure operated by buttons. 
 If we look for chemical actions within this pupil's sphere we find 
 them to be rather few, too familiar to hold the attention or too 
 complicated to tempt analysis. He comes in contact with but few 
 elements and but few pure compounds. Steel is to him a specially 
 pure iron, zinc is the metal used in batteries, tin used for cans, 
 
20 
 
 sulphur smells bad. He has often been told that soda water 
 contains no soda. Soap is useful in cleaning, as it eats dirt as an acid 
 "eats metal." A material involving electric means is necessarily superior. 
 The tendency to centralization in driving our small industrial estab- 
 lishments has narrowed the child's opportunities for observation. The 
 shops of the blacksmith, carpenter and soap-maker where he learned the 
 art of critical observation and learned some things not taught in school 
 have been withdrawn behind doors marked "no admission." 
 
 The classes of our large schools are mixed as to sex, race and ability. 
 It is often said with pride that our urban population is cosmopolitan, 
 but that the second generation from the emigrant is acquainted with 
 American ways. Admitting that the second generation may be some- 
 what acquainted with American ways, we must also admit that the 
 population of our large cities is becoming mongrel. The mongrel is never 
 stable and is rarely successful. The psychology of the mongrel is analogous 
 to that of the mob. Is it not then asking too much that children of one 
 or two generations from barbarity should be put through the same course 
 and be expected to meet the same educational standards as the natives 
 of Massachusetts? 
 
 The tendency of education at present is the development of power, 
 of ability to reason, to think. We may, indeed, ask if the drill along 
 this line has not been pushed so far at times as to neglect giving some- 
 thing to think about. The school, unlike the college, works by the clock, 
 the work must be cut to fit the time, thus we often find a few facts or 
 questions are presented in such a way that but one conclusion is possible. 
 This is called inductive teaching teaching to reason. 
 
 It makes the work easier for the teacher if the work can be made to 
 follow a mathematical model, so problems come to take an important 
 place. The work becomes quantitative and is now held to develop 
 thought, originality and logical reasoning. But the problem in ele- 
 mentary chemistry is usually of type form, and is not the teacher largely 
 sponging on the power drilled into the pupil by the mathematics teacher? 
 The English of the schools is criticized by college and business men alike. 
 I believe a clear, concise exposition of phenomena in correct language 
 will be of more benefit to the pupil than any number of problems in 
 chemical arithmetic. 
 
 The pupils I have in mind are the ordinary ones in large schools, thir- 
 teen to sixteen years of age, girls and boys. Only a small percentage will 
 go to college, some will go to business, some to be clerks, some home 
 makers, some teachers. They have been herded in elementary schools 
 taught at in bulk. They are deficient in English and any correct notions 
 of the activities of the world. It is the business of the high school to 
 supplement the elementary school and by its specialization correct the 
 errors of the grades and systematize the instruction. College prepara- 
 tion is only incidental. 
 
 A large amount of knowledge is not needed in practical life so much 
 as the power to do things, but knowledge certainly increases power. 
 While we must be able to do one thing well even a superficial knowledge 
 of many things is not to be despised. Good judgment, ability to arrive 
 at accurate conclusions from given data is most essential, but if we look 
 closely a large part of what is commonly called reasoning is but rehearsing 
 of formulae. Good judgment cannot be taught. So few of our pupils 
 
 132 
 
21 
 
 will ever be so situated that they need reason independently concerning 
 chemical phenomena that it is scarcely justifiable to foist the time and 
 cost of such instruction on the public. 
 
 Where and how can chemistry accomplish the most good in the school? 
 If the object of education is to develop a youth most completely, to make 
 a well-rounded individual, to make him feel an intelligent interest in the 
 activities of the world, it is not necessary that each factor in such a total 
 should be well rounded. A number of smooth, well-rounded sticks will 
 make a very insecure bundle, but if some of the tricks are somewhat 
 rough the bundle may not appear so elegant but it will be more firm. 
 Chemistry touches every phase of human activity. It requires language 
 for its expression, mathematics for its determination, physics for its 
 operation. Its history is the history of the world. 
 
 It would be impossible to find a better subject than chemistry to bind 
 together the school work, to systematically furnish splinters to make 
 the bundle strong. The domestic science teacher, the biology teacher 
 and the physics teacher give some splinters of information which they 
 call chemistry and build their work upon this basis, usually indigestible 
 definitions. A systematic course in elementary science should be placed 
 in the first year of the high school, designed to impart that information 
 of things and processes we might well expect every one to know. This 
 might be followed later by a course more thorough. 
 
 We now expect our pupils to specialize as soon as they leave the ele- 
 mentary schools and to prepare for some life work. He or she knows 
 nothing of human activities out in the every-day world ; there is practic- 
 ally no place in the school curriculum where this is taught. We have 
 trade schools, vocation schools, commercial schools, not to mention 
 others all of which require him to specialize before showing him any 
 general plan from which to choose or guiding his choice. 
 
 The pupil who will receive no further school instruction can in a year 
 be given a good knowledge, by a teacher with adequate equipment, of 
 many of the facts of elementary chemistry relating to our daily life and 
 its activities a knowledge sufficient in most cases to excite a lasting 
 interest in natural phenomena and to cause the student to seek explana- 
 tion. There is a multitude of chemical facts which concern the boy 
 who goes into the shop or office or behind the counter, and which he 
 should know. The girl who will stop at home or teaches others' chil- 
 dren is also concerned with chemical phenomena, chemical information 
 which has been crowded out of her curriculum to make room for more 
 cultured and less mussy subjects. 
 
 Adhering to traditional procedure, our science courses have become 
 pseudotheoretical or pseudotechnical ; it is time we had one systematically 
 informational and practical. Facts are as important as explanations 
 and should precede them. Such a course need not pretend complete- 
 ness in any line. It might be comparative rather than critical. It would 
 not attempt to rediscover or verify natural laws, but would aim to culti- 
 vate the powers of observation and of accuracy of description, to express 
 ideas of phenomena in simple, direct English rather than to hide incoherent 
 thought behind a big name or a slang expression. 
 
 In a first course in chemistry, atoms, molecules, ions and many other 
 terms might be omitted altogether. They are but words, the modern 
 idea of an atom is incomprehensible to one without a wide knowledge of 
 chemistry. Theory should be eliminated as much as possible, making 
 
 133 
 
22 
 
 the course treat of facts, their sequence and relation to one another. 
 Numerical problem solving should take but a small part in recitation 
 work. No more can come out of an equation than we put into it. It 
 cannot develop originality. 
 
 Such a course for children of twelve to thirteen years would need sim- 
 plicity in its treatment. Faraday's lectures to children are a model in 
 this respect. Ostwald's "Conversations" show how some complicated 
 things may be dealt with simply. 
 
 I would have such a course give information concerning natural phe- 
 nomena and the work of man, show what is being done, and how, with- 
 out technical detail. 
 
 I would give the pupil something to know. Facts that are worth know- 
 ing in and of themselves facts that concern himself, his food, his cloth- 
 ing, his shelter and his work. Concerning the things he or she will meet 
 in life, no matter whether the future be as a chemist, a bookkeeper or in 
 the kitchen. The material is ample. 
 
 The subject might be systematized by its applications rather than 
 the traditional order. Study topics rather than elements; study deter- 
 gents, not soap; study bleaching rather than peroxide or bleaching pow- 
 der. The development of the race through the stone, bronze and iron 
 age has depended largely upon his chemical knowledge. Let us study 
 the metals in their metallic aspects rather than according to the periodic 
 table. 
 
 Foods, clothing, materials of utility and convenience or of commerce 
 often can not be rationally treated by the present systems of our texts, 
 but a suitable systematization might easily include these ; what they are, 
 how they are produced and what they do. 
 
 In its effects upon the pupil and school, we may be sure that pupils 
 who have seen something of the general trend of the instruction through 
 a systematic preliminary course will feel more interest to continue study 
 and will accomplish more and better work in later courses. 
 
 MICHAEL D. SOHON. 
 
 MORRIS HIGH SCHOOL, 
 NEW YORK, N. Y. 
 
 134 
 
RADIOACTIVITY. 1 
 
 BY ANDRE DEBiERNE. 2 
 Received July i, 1911. 
 
 Radioactivity comprises to-day a very large number of facts and theo- 
 ries of which it would not be possible to give a complete survey in a brief 
 address. Nevertheless, I shall make an effort to bring out all the chief 
 points of interest of the new science, the birth of which may be consid- 
 ered without exaggeration as the most important scientific event of the 
 past few years. 
 
 Not only has this new science revealed the existence of extremely curious 
 substances and brought a rich harvest of new natural phenomena, but 
 it has led us to the attack of a problem which seemed absolutely chimer- 
 ical only a few years ago the problem of the transmutation of atoms 
 or of the chemical elements; for it is now demonstrated that the phe- 
 nomena of radioactivity are concomitants of the disintegration of atoms. 
 Radioactivity may now be defined as the science of atomic transforma- 
 tions; it is not impossible that in time radioactivity may become the art 
 of changing chemical elements into one another. The facts known at 
 present leave no doubt as to the reality of atomic disintegrations; if as 
 yet these transformations are entirely beyond our control, possibly some 
 day we may learn how to bring them about and to control them. 
 
 The fundamental phenomenon, which was discovered by Henri Bec- 
 querel and has served as the point of departure for the development of 
 radioactivity, is as follows: Certain substances emit spontaneously a 
 peculiar radiation whose properties are analogous to those of the rays 
 obtained in a Crookes tube. The new rays render gases conductors of 
 electricity, act on a photographic plate, and produce fluorescence in certain 
 substances. This spontaneous emission of rays was first observed in the 
 case of uranium and its compounds, later also in the case of thorium com- 
 pounds. Then were discovered new substances possessing the same 
 property in a very high degree. All these substances are said to be 
 radioactive. They constitute a new source of energy. 
 
 An apparently essential characteristic of the phenomenon of radio- 
 
 1 A summary presented at the Second Decennial Celebration of Clark University, 
 Worcester, Mass., September 17, 1909. 
 
 2 Translated from the French by M. A. Rosanoff. 
 
 135 
 
1389 RADIOACTIVITY. 
 
 activity is its spontaneity : the emission of rays takes place without visi- 
 ble external cause. This characteristic permits of distinguishing the 
 phenomena of radioactivity from those that take place in the course of 
 certain chemical reactions. For instance, the oxidation of phosphorus 
 is accompanied by phosphorescence and by electrical conductivity of the 
 gases surrounding the phosphorus. The same phenomena may be brought 
 about by the action of heat upon the sulfate of quinine. But in all such 
 cases the phenomenon is not spontaneous ; it is brought about by external 
 causes which are easy to detect. Therefore, phosphorus and quinine 
 sulfate are not considered as radioactive substances. 
 
 Another essential characteristic was brought out by the early researches 
 of Madame Curie. Radioactivity is an atomic property. The spon- 
 taneous emission of rays is connected with the radioactive atom, and is 
 not in the slightest degree influenced either by changes of state of aggre- 
 gation of by chemical combination with the atoms of other elements. 
 Thus, the intensity of the Becquerel rays emitted by the substances con- 
 taining uranium, and measured by the conductivity of the surrounding 
 gases, is always proportional to the number of uranium atoms contained 
 in the substance and is independent of the form in which uranium may 
 be present. Among the numerous other properties of matter, mass alone 
 is so distinctly atomic in its nature. 
 
 Our realization of the atomic character of the radioactive property has 
 had a directing influence on the science of radioactivity and has led to 
 the establishment of its present theories. But first of all it had led to 
 the discovery of radium itself and of the other strongly radioactive sub- 
 stances. I shall review briefly the genesis of the discovery of radium, 
 which forms one of the most beautiful investigations ever carried out 
 in the physical sciences, both as regards the logical keenness with which 
 the research was carried on and as regards the material difficulties which 
 had to be overcome. The novel method employed has since been con- 
 stantly used in researches in radioactivity. 
 
 Among the elements that had previously been known, only uranium 
 and thorium were radioactive, and the activity of any substance con- 
 taining one of these elements was found to be proportional to the quan- 
 tity of the active element present. Certain minerals, however, contain- 
 ing uranium showed a greater activity than metallic uranium itself. 
 Pierre Curie and Madame Curie, thoroughly convinced of the atomic 
 nature of radioactivity, assumed that these minerals contained new 
 chemical elements, endowed with greater activity than uranium, and al- 
 though physicists by profession, and with only rudimentary laboratory 
 means at their disposal, they undertook a search after the new hypo- 
 thetical elements. 
 
 I cannot depict here all the difficulties that presented themselves in the 
 search, which involved the chemical treatment of tons of material. Suffice 
 it to recall the results obtained by Pierre Curie and Madame Curie after 
 several years of uninterrupted effort. Those results fulfilled their expec- 
 tations entirely. The minerals studied do contain strongly radioactive 
 compounds, whose radioactivity is due to the presence of new chemical 
 elements. In the case of one of these elements, namely radium, it has 
 been possible to prepare a series of pure salts; further, its spectrum has 
 been studied, its atomic weight determined and a place has been 
 
 136 
 
GENERAL, PHYSICAL AND INORGANIC. 1390 
 
 assigned to it in the periodic classification of the elements. Radium has 
 become a marvelous instrument of research, and to it we owe all the 
 most important discoveries in radioactivity. 
 
 It was soon recognized that radioactive substances may differ from 
 one another, not only in intensity of radiation, but also in the character 
 of radiation and in certain peculiarities in the mode of emission of the 
 rays. On the basis of these properties it is as easy to recognize a given 
 radioactive element with certainty as it is to recognize one of the older 
 elements with the aid of spectrum analysis. 
 
 The principal new radioactive substances are polonium and radium, 
 discovered by Pierre Curie and Madame Curie; actinium, discovered by 
 myself shortly afterwards; radio-thorium, discovered by Hahn; and 
 ionium, discovered by Rutherford and Boltwood. However, certain 
 of these substances are really complex mixtures containing entire fami- 
 lies of chemical elements: namely, the thorium family, the radium family, 
 and the actinium family. 
 
 The rays emitted by radioactive substances may be subdivided into 
 three groups, viz., the a rays, the /? rays, and the ? rays, which are analo- 
 gous to the three groups of rays emitted in a Crookes tube, viz., canal 
 rays, cathode rays, and Roentgen rays. The a rays are constituted by 
 the projection of positively charged particles ; the ft rays by a projection 
 of negatively charged particles; the f rays are not charged at all. 
 
 The particles of /? rays are electrons, and the rays are easily bent out of 
 their path by a magnetic field. Certain /? rays are constituted by elec- 
 trons projected with an extremely great velocity, a velocity approach- 
 ing that of light, and it has been possible to verify on these rays an im- 
 portant deduction from the electron theory. For very great velocities, 
 namely, the inertia of a particle ceases to be a fixed quantity; it may 
 greatly increase with increased velocity of motion, and so the particle no 
 longer obeys the laws of Newtonian mechanics. Finally, comparing 
 (3 rays and cathode rays, one finds them analogous, only the particles of 
 ft rays move with greater velocity and are capable of penetrating a much 
 thicker layer of matter (for instance, a plate of aluminium one mm. 
 thick). 
 
 The a rays are constituted by the projection of material particles, 
 charged electro-positively, having the dimensions of atoms, and moving 
 with a smaller velocity than the particles of /? rays. The a rays are bent 
 by a magnetic field with considerable difficulty, and can penetrate only 
 a very thin layer of matter (aluminium foil V 20 mm. thick absorbs them 
 completely). They have the peculiarity of suddenly stopping after 
 having traversed a certain well-determined path in a given medium. 
 The length of this path in air is a very important quantity, for it permits 
 of distinguishing from one another the different species of a rays and 
 consequently also the different radioactive substances. The a particles 
 play a very important part in radioactive transformations, and their 
 nature seems now to be clearly understood. 
 
 The f rays are not charged, and therefore are not deflected by a mag- 
 netic field. They suffer but slight absorption in matter (a considera- 
 ble proportion of the 7- rays from radium passes through a lead plate 
 one centimeter in thickness). 
 
 These several rays excite fluorescence in a number of substances (platino- 
 
 137 
 
1391 RADIOACTIVITY. 
 
 cyanide of barium, sulfide of zinc, uranyl salts, glass, paper, diamond, 
 etc.). The action of a rays upon zinc sulfide produces the very peculiar 
 phenomenon generally designated by the term scintillation; in this, the 
 luminosity of the zinc sulfide screen is caused by an infinity of brilliant 
 little points which appear and disappear continually and which are clearly 
 distinguishable when the screen is examined with a lens. 
 
 The radioactive substances constitute a new source of energy ; but dur- 
 ing the earlier researches both the origin and the mechanism of this pro- 
 duction were entirely unknown. Pierre Curie and Madame Curie ad- 
 vanced two distinct hypotheses to explain the production of this energy. 
 The first hypothesis assumed that the energy was furnished from outside 
 in the form of a special radiation, causing in the radioactive substances 
 a phenomenon analogous to phosphorescence. According to the second 
 hypothesis, the energy comes from the active substance itself, and hence 
 the emission of energy must be accompanied by a change in the substance. 
 Pierre Curie and Madame Curie, who had demonstrated the atomic char- 
 acter of the new property, believed thoroughly, even before radium had 
 been discovered, that the transformation takes place in the radioactive 
 atom itself, which must therefore change into a different atom and, con- 
 sequently, gradually disappear in course of time. It is this hypothesis of 
 atomic transmutation that has proved to be most fruitful and has formed 
 the basis of the theories accepted at present. 
 
 The principal fact which has led to these theories is as follows: With 
 the aid of radioactive substances, whose activity appears constant and 
 permanent, it is possible to produce phenomena of radioactivity whose 
 intensity diminishes in time. These phenomena of temporary activity 
 may be observed under various circumstances. Thus, if any substance 
 whatever is placed near a salt of radium, thorium, or actinium, the sur- 
 face of the substance becomes radioactive, and this activity diminishes 
 more or less rapidly in time. This is the phenomenon of induced radio- 
 activity discovered by Pierre Curie and Madame Curie. Similarly, any 
 gaseous atmosphere surrounding radium, thorium, or actinium, becomes 
 itself radioactive, and its activity likewise diminishes in time. Ruther- 
 ford, the discoverer of this last phenomenon, gave the name "emana- 
 tion" to the cause of the temporary activity of the gases. Finally, as 
 first observed by myself, in the case of actinium, substances temporarily 
 radioactive may also be obtained through certain chemical separations 
 in mixtures containing permanently radioactive substances. 
 
 These temporary radioactivities often follow complex laws of de- 
 crease. The study of these laws has shown that there exist really several 
 different kinds of radioactivity succeeding one another in time. When 
 one kind of activity has died out, another replaces it, and this may grad- 
 ually cease to exist in its turn. Each kind of radioactivity is character- 
 ized by its own velocity of decrease and by a radiation peculiar to itself. 
 Extraordinarily great temporary radioactivities may accumulate in an 
 extremely slight quantity of matter. 
 
 Applying to these temporary radioactivities the idea which had guided 
 to the discovery of radium, namely, that radioactivity is an atomic prop- 
 erty of the elements exhibiting it, one is led to think that the temporary 
 radioactivities which have been separated from radium, thorium, and 
 actinium characterize new radioactive atoms. And, accepting the 
 
 138 
 
, PHYSICAL AND INORGANIC. 1392 
 
 hypothesis of atomic transmutation as an explanation of the origin of 
 radioactive energy, the decrease of a given radioactivity appears to re- 
 sult from the gradual disappearance of a radioactive element and its 
 transmutation into another element. 
 
 The present theory of radioactive phenomena is based on these con- 
 siderations. It was proposed by Rutherford and Soddy, who have 
 published numerous observations in complete accord with it. At pres- 
 ent the theory is accepted by all investigators of radioactivity. An 
 extremely precious guide in research, it has again and again been con- 
 firmed by discoveries of great importance. 
 
 The various phenomena exhibited by radium may, then, be interpreted 
 as follows : The radium atom, which emits a certain a radiation, produces 
 continually a radioactive emanation. This emanation is considered 
 to be a radioactive gaseous element resulting from the transmutation 
 of radium, and hence the latter must gradually disappear in time. The 
 emanation emits an a radiation different from that of radium and disap- 
 pears quite rapidly (the decrease follows a simple exponential law and 
 amounts to one-half in 3.8 days). The emanation produces deposits of 
 induced radioactivity, which are considered as new elements resulting 
 from the transmutation of the emanation. In these deposits it has been 
 possible to identify a series of stages which have received the names of 
 Radium A, Radium B, Radium C, and which succeed one another, radium 
 A changing into radium B, which in turn changes into radium C. These 
 different members of the group emit different radiations and undergo de- 
 struction with considerable velocities. 
 
 Following radium C is another sequence of terms, characterized by a much 
 smaller rate of disappearance, viz., Radium D, Radium E t , Radium E 2 , 
 and Radium F. The last-named has been shown by Rutherford to be 
 identical with polonium. Polonium itself disappears little by little, but 
 the element succeeding it is as yet unknown. 
 
 It has been possible to determin with much precision the laws of forma- 
 tion and destruction of the different transition terms of the series. These 
 laws are exponential expressions analogous to those which hold for mono- 
 molecular chemical reactions. Most of the terms have been isolated 
 (by means of chemical reactions, electrolysis, heating, condensation at 
 low temperatures, etc.), and the several exponential formulas followed by 
 their rates of destruction have been determined separately, the formula 
 corresponding to each term having a characteristic exponent, X, of its 
 own. The rate of destruction of a given term is frequently characterized 
 by specifying the time T required to diminish by one-half the original 
 intensity of its radiation. The quantity i/^ may be considered as the 
 mean duration of life of an atom of the substance under consideration; 
 it is denoted by the symbol and is usually referred to briefly as "the 
 mean life." We have, then, = i/k and T = @hi2. 
 
 The numerous researches which have been carried out on radioactive 
 substances have resulted in fairly complete knowledge concerning the 
 series of radioactive transformations in the several families, the proper- 
 ties of the different terms, and the properties of the rays emitted during 
 the transformations. The knowledge gathered up to the present time is 
 reproduced in the accompanying tables. 
 
 139 
 
1393 
 
 RADIOACTIVITY. 
 
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 143 
 
1397 RADIOACTIVITY. 
 
 The inter-relation between the different terms of one and the same 
 family is not the result of theoretical interpretation. It is a thoroughly 
 established experimental fact. According to present-day theory, each 
 term represents a certain chemical element which differs from the ordi- 
 nary elements only by its ephemeral existence and by its emitting a special 
 radiation. The disappearance of the radioactive atom is the result of its 
 transformation into another atom, the special radiation representing 
 the energy which accompanies that transformation. According to this 
 theory, then, the study of radioactivity has led to the discovery of some 
 thirty new elements. 
 
 The theory outlined above permits of an easy interpretation of all 
 phenomena thus far known. Still, it was a matter of great importance to 
 obtain a direct experimental demonstration of the reality of atomic 
 transformations, and of the existence of chemical atoms having a very 
 short life, corresponding to the ephemeral radioactivities. Such direct 
 experimental demonstrations have actually been produced, and hence 
 the theory rests on an extremely solid basis. 
 
 The reality of atomic transformations accompanying the phenomena of 
 radioactivity has been demonstrated by the experiments of Ramsay 
 and Soddy on the production of helium from radium. Radium, whose 
 character as a chemical element is established by its chemical properties, 
 by its atomic weight, and by its spectrum, continually produces the gas 
 helium, which is itself a well characterized chemical element. This pro- 
 duction of helium cannot be reasonably interpreted in any other way 
 than by recognizing atomic transformation. 
 
 Some time after Ramsay and Soddy, I showed that the same phenom- 
 enon takes place in actinium, which also continually produces helium 
 gas. Recently, Soddy has discovered the production of helium also 
 from uranium and from thorium. 
 
 The production of helium from radioactive substances is the first 
 case ever discovered of the transformation of chemical atoms. 
 
 That an ephemeral radioactivity is due to the existence of a corre- 
 sponding chemical element has been experimentally demonstrated in 
 the case of the radium emanation. This emanation has been isolated 
 in a pure state, its spectrum determined, and its volume measured. 
 Somewhat numerous experiments were first carried out by Ramsay 
 and his collaborators, and though the published results are not in per- 
 fect agreement, they still leave no doubt whatever as to the material 
 existence of the emanation, which is characterized by a spectrum of its 
 own. The isolation of the substance was effected by utilizing its property 
 of easily condensing at low temperatures. These experiments were later 
 repeated by Rutherford and Royds, who obtained agreeing measure- 
 ments of the volume occupied by the pure emanation produced by a given 
 quantity of radium, and who described completely the spectrum of the 
 emanation. Recently, I have carried out analogous experiments: my 
 volume measurements agree perfectly with Rutherford's, and my spectro- 
 photographs are identical with those of Rutherford and Royds. I have 
 observed besides that the volume of gas produced does not increase pro- 
 portionally to the time, owing to the spontaneous destruction of the 
 substance. The observed volume is invariably proportional to the radio- 
 activity of the emanation, no matter what the duration of its produc- 
 tion from radium. In the experiments mentioned above, all investiga- 
 
 144 
 
GENERAL, PHYSICAL AND INORGANIC. 1398 
 
 tors have observed the production of helium from the emanation: the 
 spectrum of helium gradually appears, while that of the emanation dis- 
 appears. Finally, Rutherford, and also Ramsay, have succeeded in de- 
 termining the point of liquefaction and the point of solidification of the 
 emanation. 
 
 It thus appears entirely certain that the emanation is a material gas 
 a fact which corroborates very strongly Rutherford and Soddy's theory. 
 
 The production of helium by radioactive substances is directly rela- 
 ted to the emission of a particles, and the hypothesis early advanced 
 by Rutherford, that each a particle is an atom of helium, is to-day con- 
 firmed. In fact, Rutherford has shown that the a rays and the helium 
 produced by the radium emanation pass through thin layers of matter 
 in a similar manner. Other properties of the a particles are in complete 
 accord with this conception of their nature. 
 
 Now, if we assume that in all transformations accompanied by the 
 emission of a. particles each radioactive atom changes into the next in 
 order by loss of a single a particle or helium atom, it becomes possible 
 to calculate the atomic weights of the several transition elements of the 
 radium series. The atomic weight of helium being 4, we have, namely: 
 Radium 226.5 > Emanation 222.5 > Radium A 218.5 * 
 Radium B 214.5 > Radium C 214.5 > Radium D 210.5 > 
 Radium E 210. 5 > Radium F, or Polonium, 210. 5 > a last unknown 
 substance 206.5. This l as * number represents exactly the atomic weight 
 of lead, which suggests the idea that this element is the final product 
 of the transformation of radium. It is probable that this idea can be 
 subjected to experimental verification. 
 
 The mother substances, uranium, radium, actinium, and thorium, 
 ought to gradually disappear in course of time, as they are transformed 
 into other elements. But the destruction is certainly very slow, and no 
 diminution of their activity has been directly detected. The laws of 
 their destruction may, however, be determined indirectly. Since the 
 transformation of each radioactive atom produces an emission of rays, 
 it is natural to assume that the more intense the radiation produced by 
 a gram-atom of the substance, the more rapid is the transformation. 
 Thus, radium ought to have a much shorter life than uranium or thorium. 
 The comparison of the radiations may be carried out quantitatively, 
 and thus the ratio of the mean lives of two radioactive substances may 
 be readily obtained. 
 
 On the other hand, if it is assumed that the emission of a single a par- 
 ticle corresponds to the transformation of a single atom, it will suffice 
 to determin the number of particles emitted per second by a given mass 
 of the active substance under consideration, in order to ascertain its 
 velocity of transformation. Indirect determinations were first made by 
 measuring the total positive charge emitted in the form of a rays by the 
 active substance and making an assumptiion concerning the charge of a 
 single particle. The results so obtained have been confirmed by directly 
 counting the a particles emitted by a certain quantity of active sub- 
 stance. 
 
 The first direct results were yielded by the scintillations produced by 
 a particles on a screen of zinc sulfide. Each scintillation being assumed 
 to be produced by a single a particle, the number of scintillations was 
 
 H5 
 
1399 RADIOACTIVITY. 
 
 determined, produced in a given time by . known quantity of the active 
 substance. This gave the number of a particles emitted by the sub- 
 stance, and consequently the number of atoms transformed in a given 
 time. Another, and very ingenious, method was first employed by 
 Rutherford and Geiger, who utilized the ionization produced in a gas by a 
 particles. These investigators succeeded in determining the ionizing 
 effect produced in a rarefied gas by each a particle by making use of the 
 phenomenon of ionization by shock. The entrance of each single a par- 
 ticle into the gas affects the electrometer, and all that is necessary is to 
 count the number of disturbances produced in a given time. The two 
 methods have yielded well agreeing results, which indicate that radium 
 ought to be one-half destroyed in about 2000 years. 
 
 The destruction of radium is too slow to be capable of being detected 
 by direct experiment. Nevertheless, in order to account for the presence 
 of radium in minerals, it is necessary to assume that radium is continually 
 produced in those minerals, the destruction being thus partly compensa- 
 ted for. The element which appears evidently to be the most capable 
 of changing into radium is uranium. 
 
 In fact, radium is always found in uranium minerals and, furthermore, 
 uranium is radioactive and hence in a state of decomposition. Since the 
 radioactivity of uranium is much less intense than that of radium, its 
 duration of life must be much greater than that of radium, and this ex- 
 plains the occurrence of uranium in considerable quantities in nature. 
 
 An extremely important argument in support of the accepted rela- 
 tionship between uranium and radium lies in the constant ratio of the 
 quantities of the two elements found in minerals. The constancy of this 
 ratio, which has been principally affirmed by the experiments of Bolt- 
 wood, is readily explained if we assume that radium is produced from 
 uranium, and that the destruction of radium is much more rapid than that 
 of uranium. The ratio permits of calculating the mean life of uranium. 
 
 Attempts to demonstrate directly the formation of radium from ura- 
 nium have shown that this transformation is certainly not immediate, 
 and that there ought to exist at least one substance intermediate between 
 uranium and radium. This has been confirmed by Rutherford and 
 Boltwood's discovery of a new substance capable of producing radium. 
 This new substance has been named ionium. The mean life of ionium 
 being probably long, there is hope that this substance will be isolated 
 without much difficulty. 
 
 The question of the relationship between uranium and radium seemed 
 to be definitly settled, when recently Mile. Gleditsch announced that 
 the ratio of the quantities of uranium and radium was not the same in all 
 minerals, contradicting the earlier results of Bolt wood. While the 
 ratios found by Mile. Gleditsch are of the same order of magnitude, 
 they nevertheless differ very materially from one another. The hypothesis 
 of the formation of radium from uranium furnishes so simple an explana- 
 tion of the presence of radium in minerals that one can hardly abandon 
 it. As a matter of fact, however, the conditions of formation of radium 
 appear to be complex and not yet completely elucidated. Unquestion- 
 ably, further study of the relative quantities of the different active sub- 
 stances in minerals will yield new and important results. Such study 
 will also be of great usefulness in geology. 
 
 146 
 
GENERAL, PHYSICAL AND INORGANIC. 1400 
 
 If the phenomena of radioactivity indicate atomic transformation, one 
 expects to find radioactive energy, corresponding to the transformation 
 of atoms, to be far greater than the energy changes generally accompany- 
 ing the transformation of molecules. That this is true is shown by Pierre 
 Curie and Laborde's discovery of the enormous quantity of energy given 
 off by radium. One gram of radium in radioactive equilibrium would 
 produce about 1 20 calories of heat in an hour. The quantity of heat that 
 would be set free by the complete transformation of one gram of radium 
 is nearly the same as that produced by the combustion of a ton of coal. 
 Most of this heat has been shown to come from the kinetic energy of the 
 a particles. Heat has also been shown to be developed by actinium, 
 thorium, and polonium. Radioactivity thus constitutes an extremely 
 important source of energy. A very slight proportion of radium in the 
 sun (about i gram per cubic meter) would be sufficient to account for 
 all the energy radiated by it. The energy radiated by our own planet 
 seems to be more than compensated for by the radium contained in its 
 crust, so that the progressive cooling of the earth, once generally accepted, 
 now seems to be problematic. It seems legitimate to assume that radio- 
 activity constitutes one of the principal sources of the energy radiated 
 in the universe. No other hypothesis is based on an equally serious ex- 
 perimental foundation. 
 
 The atomic transformation of radioactivity takes place under very pecul- 
 iar conditions. As already stated, the phenomenon is spontaneous, 
 apparently causeless. Moreover, no method is as yet known by which 
 such transformations might be brought about or stopped, or even in the 
 least degree hastened or slowed up. Elevation of temperature, which is 
 so sure to increase the velocity of chemical reactions, seems to have no 
 effect whatever on radioactive transformations. Thus, the characteris- 
 tic constant of the destruction of radium emanation is the same at high 
 temperatures as at the temperature of liquid air. Neither does the 
 nature of an inactive chemical element combined with the radioactive 
 atom seem to have any influence upon the velocity of its destruction. 
 As yet, we are mere spectators, observing the transformation of atoms, 
 but unable to interfere with it in any way. 
 
 The transformation follows a probability law identical with the law of 
 mass action followed by chemical reactions: the number of atoms trans- 
 formed per unit of time is at any instant proportional to the total number 
 of atoms present. No simple and satisfactory hypothesis, however, has 
 been advanced explaining this fact. In the case of mono-molecular 
 chemical reactions, the fact that the transformation takes place grad- 
 ually is explained on the assumption that all the molecules present are 
 not in the same condition, either owing to collisions between the mole- 
 cules or because of differences in whatever motion may be going on within 
 the molecules themselves. The transformation of a given molecule is 
 instantaneous, but the molecule will not undergo transformation unless 
 it happens to get into a certain condition necessary for it. The proba- 
 bility law must then remain the same as long as the number of molecules 
 remains very great and the external conditions of the reaction remain 
 the same. In the case of radioactive transformations, external condi- 
 tions (e. g., of temperature) and intermolecular collisions ought to have 
 no effect. Therefore, only the motion within the interior of the atom 
 
 147 
 
1401 RADIOACTIVITY. 
 
 can be invoked in an effort to explain why, in one and the same substance, 
 some atoms break down immediately after being formed, while others 
 are destined to live hundreds or even thousands of years before under- 
 going transformation. 
 
 It is imaginable that there exists in space a special field of force which 
 influences intra-atomic motion and is therefore capable of causing the 
 disintegration of atoms. The action of such a force must then be inde- 
 pendent of any translatory motion of the atoms. There is, however, at 
 present absolutely no indication of the existence of such a force in space. 
 
 If the transformation is not brought about by an external force, and if 
 external conditions of pressure, temperature, etc., have really no influ- 
 ence upon the progress of radioactive changes, one is led to assume 
 that the destiny of a given atom is completely determined at the very 
 moment of its formation, that at that moment it is already in such a state 
 that its transformation must take place after exactly a certain interval 
 of time. In that case a radioactive element must be considered as 
 made up of atoms of different nature, some destined to very speedy de- 
 struction, others to a more or less prolonged existence. It is not un- 
 thinkable that these different atoms of one and the same radioactive ele- 
 ment may some day be separated. 
 
 In order to account for the exponential law of spontaneous destruction, 
 it is necessary, in that case, to assume that the distribution of life dura- 
 tions among the atoms at the moment of their formation is represented 
 by a simple exponential function, the atoms of short life being much more 
 numerous than those of long life. It is, however, difficult to imagine 
 what can possibly be the cause of such a law of distribution, and con- 
 siderations like the above only show that while the laws of radioactive 
 transformations have been determined with precision and are well 
 known, the initial cause of the phenomena is as yet altogether obscure. 
 
 In concluding this summary, I will mention the attempts that have 
 been made with a view to artificially bringing about atomic transforma- 
 tions with the aid of radioactive energy. Some results in this connec- 
 tion have been published by Ramsay and Cameron. They believed 
 that by the action of radium emanation upon water they had succeeded 
 in producing neon. They further believed that by the action of the 
 emanation upon a salt of copper they had produced alkali metals: the 
 formation of lithium appeared to have been especially well demonstrated. 
 
 These results have, unfortunately, been shown to be erroneous. Mme. 
 Curie and Mile. Gleditsch repeated the experiments on the formation of 
 lithium and found that when no other than platinum vessels were used, 
 the appearance of lithium could not be detected ; in Ramsay and Cameron's 
 experiments the lithium came from the glass of the apparatus employed. 
 Similarly, Rutherford and Royds have re-investigated the effect of emana- 
 tion upon water and have failed to obtain any neon. I, too, have failed 
 to find neon in the gases evolved by a solution of radium. The neon 
 found by Ramsay and Cameron must have come from a small quantity 
 of air introduced by accident. 
 
 So it may be said that up to the present time no atomic transmutation 
 has been produced artificially. All we can do is to subject to inquiry 
 spontaneous transmutations which we cannot control. A long step, 
 
 148 
 
GENERAL, PHYSICAL AND INORGANIC. 1402 
 
 therefore, remains to be taken before the dream of the alchemists 
 has been realized. 1 
 
 CLARK UNIVERSITY. WORCESTER. MASS. 
 
 1 New results have been published by Ramsay and Gray. According to these 
 investigators, carbon dioxide may be produced by the action of radium emanation 
 upon compounds of thorium, zirconium, silicon, etc. But inasmuch as carbon com- 
 pounds may easily find their way into apparatus by accident, it is difficult to establish 
 beyond doubt a transformation of the elements thorium or zirconium into carbon. 
 The authors themselves admit that their experiments are not conclusive. 
 
 149 
 
Duplicate 
 Stanford Lib.