LIBRARY 
 
 UNIVERSITY OF CALIFORNIA. 
 
 GIFT OF" 
 
 Class 
 
 
The University of Chicago. 
 
 Founded by JOHN D. ROCKEFELLER. 
 
 On the Oxygen Ethers of Urea* 
 
 A DISSERTATION 
 
 SUBMITTED TO THE FACULTIES OF THE GRADUATE 
 
 SCHOOLS OF ARTS, LITERATURE, AND SCIENCE, 
 
 IN CANDIDACY FOR THE DEGREE OF DOCTOR 
 
 OF PHILOSOPHY. 
 
 DEPARTMENT OF CHEMISTRY. 
 
 BY WILLIAM McAFEE BRUCE. 
 
 EASTON, PA. : 
 
 Press of the Chemical Publishing Co. 
 1904. 
 
ON THE OXYGEN ETHERS OF UREA. 
 
 investigations on the oxygen ethers of the ureas as carried 
 on in this laboratory by F. B. Dains 1 and R. H. McKee, 2 under 
 the direction of Professor Stieglitz, 3 have been continued by me 
 at the latter's suggestion, with the object of studying the isourea 
 ethers from points of view which it was impossible to include 
 in the work done by Dains and McKee. 
 
 A more detailed study was first made of the chemical nature 
 of the acylisoureas. Stieglitz and McKee 4 found that by the 
 action of acylchlorides on monosubstituted isoureas, two series 
 of isoureas may be obtained, the symmetric acylisourea ethers, 
 
 RCO.RHC(OR'):NR" (I) 
 and the asymmetric ethers, 
 
 RCO.NR"C(OR') : NH (II). 
 
 These ethers are very sensitive to hydrogen chloride, which in 
 aqueous solutions at low temperatures converts them into acyl- 
 ureas, with an evolution of alkyl chloride, R'Cl. 5 We have been 
 able to show that the loss of alkyl chloride is always preceded by 
 the formation of hydrochlorides, which were isolated and analyzed 
 and found to be very unstable. In some cases the salts lose methyl 
 or ethyl chloride spontaneously at ordinary temperatures. The 
 basic character of the acylisoureas was also confirmed by the 
 preparation of a number of chlorplatinates. 
 
 The acylisourea ethers of the first series (I) also have acid 
 properties : McKee had observed that methyl benzoylphenyliso- 
 urea is soluble in alkalies as well as in acids, but had not under- 
 taken the isolation of any of these salts. We have been able to 
 prepare silver and sodium salts of several derivatives of this 
 series, thus establishing the fact of their dual or amphoteric char- 
 acter as bases and acids. On the other hand, we found that 
 
 1 J. Am. Chem. Soc., ai, 136 (1899). 
 2 Am. Chem.J., 26, 209 (1901). 
 
 * Ibid., ai, 101 (1899); Ber. d. chem. Ges., 32, 1494 (1899); 33, 807 and 1517 (1900). 
 
 * Loc. cit. 
 
 6 Stieglitz, McKee : Loc. cit; Wheeler and Johnson : Am. Chem. /., 34, 216 (1900). 
 
 143986 
 
acylisoureas of the second series (II) have no acid properties. 
 McKee's observation that they were soluble in alkalies was con- 
 firmed, but it could be readily proved that in dissolving they are 
 saponified to the acids and the free isoureas, the latter of which, 
 as will be shown below, again have the property of forming salts 
 with both acids and bases. 
 
 Acylisoureas of the first series can also be easily obtained by 
 the action of ammonia or amines on acylimido monothiocarbonic 
 ethers, by the method of Miquel, 1 as improved by Loessner, 2 
 Dixon, 3 and especially by Wheeler and Johnson. 4 The formation 
 of metal salts of these symmetric acylisoureas and the ready 
 saponification of the asymmetric acyl derivatives under the in- 
 fluence of alkalies made it appear possible to accomplish the 
 saponification also of the symmetric acylisoureas under conditions 
 which would permit the isolation of the free isourea ethers and 
 thus make Dixon's method available for the preparation of the 
 isourea ethers themselves. Such a method would be desirable as 
 the practical variation of the nature of the alcohol radical, R' 
 (see I) is very limited in our present methods for preparing 
 isoureas and nearly unlimited in Dixon's method of preparing the 
 acyl derivatives. But all attempts to saponify the symmetric acyl- 
 isoureas without completely decomposing the isourea radical were 
 unsuccessful; very small quantities or none of the free isourea 
 ether could be isolated. 
 
 Perhaps the most interesting observation which we have made 
 on the acylisourea ethers is that we have been able to verify a 
 suspicion entertained two years ago, that the isomers of asym- 
 metric series (II) are rearranged spontaneously, but gradually 
 into the more stable symmetric isomers I. The action is as fol- 
 lows: 
 
 RCO.NR"C(OR'): NH (NR"): C(OR').NH(COR). 
 The rearrangement is entirely analogous to other migrations of 
 acyl groups from oxygen or nitrogen atoms to more basic neigh- 
 boring amine groups, e. g., to the rearrangement of orthoamino- 
 phenylcarbonates to oxyphenylurethanes, as extensively studied 
 
 1 Ann. chim.phys., (5) n, 318 (1877). 
 tj.prakt. Chent., (2), 10, 237 (1874). 
 *J. Chem. Soc. (L,ondon), 75, 380 (1899). 
 * Loc. cit. 
 
by Stieglitz and Ransom, 1 and Stieglitz and Upson. 2 The rear- 
 rangement is also analogous to that of the isomeric acylthioureas, 
 as studied by Professor H. L,. Wheeler, 3 and in order not to inter- 
 fere with Professor Wheeler's investigations, we have made no 
 further study of the rearrangement of our asymmetric acylisourea 
 ethers beyond the establishment of the above fact. 
 
 In their work on the oxygen ethers of the ureas in this lab- 
 oratory, Dains and McKee studied, in particular, to what extent 
 these ethers exhibited the reactions of ethers and notably of the 
 imido ethers to which they are closely allied. In the second part 
 of this work attention was directed especially to a study of the 
 character of the isoureas as amidines. Methylisourea, as its con- 
 stitution shows, may be considered to be an amidoformimido 
 ether, or methoxyformamidine. The study was especially in- 
 viting, because in one important particular the isoureas seemed 
 to show a marked difference from other amidines of the aliphatic 
 series, as studied by Pinner. This was in the fact that the iso- 
 ureas can be readily isolated as free bases and are comparatively 
 stable bodies, whereas Pinner's aliphatic amidines are described 
 as very unstable bodies, hardly any or none of which can be pre- 
 pared as free bases. 4 The isoureas give the most important reac- 
 tions of amidines. In particular they condense very readily with 
 yff-oxy acid esters to form pyrimidines according to : 
 
 (RO)(NH 2 )C : NH -f CH 3 C(OH):CHCOOR > 
 
 NH.(RO)C : N.C(CH 3 ): CH.CO. 
 
 i i 
 
 They also form condensation products with oxalic ether, produc- 
 ing oxygen ethers of parabanic acid : 
 
 (RO)NH 2 .C : NH + (COOR) 2 NH(RO).C :N.CO.CO. 
 
 \ 1 
 
 They form, therefore, a very convenient starting-point for the 
 synthesis of the oxygen ethers of the ureides. 
 
 Whereas in these reactions both the nitrogen groups react read- 
 ily probably on account of the great tendency to form five and 
 
 1 Am. Ckem.J., 23, i (1900). 
 
 2 Vide, a later report. 
 
 3 Am. Chem.J., 37, 270 (1902). 
 
 * Pinner: " Imidoather," p. 90 (1892). 
 
six atomic rings only one group is, as a general rule, 1 reactive 
 when no ring formation occurs. Thus only one amine group is 
 attacked by benzaldehyde a benzylidenediisourea being formed, 
 viz. : 
 
 C 6 H 5 CH[N:C(NH 2 )OCH 3 ] 2 . 
 
 Acetyl chloride, chlorcarbonic ether and phenyl mustard oil 
 also react with but one amine group. 
 
 The oxygen ethers of phenylureas were also found to form 
 salts with metals as well as with acids a property which is char- 
 acteristic of amidines. 2 In these salts the metal is held by a nitro- 
 gen atom. 
 
 It has long been a question of considerable interest to us to 
 know just how strong the oxygen ethers of the ureas are as bases. 
 It seemed very possible that the fundamental difference in their 
 behavior as contrasted with that of the closely related group of 
 the imidoethers should be due to the former's greater strength 
 as bases and their ability to form neutral salts. 3 It was also 
 thought that it would be of interest to determine quantitatively 
 to what extent the basic properties of the ureas are increased by 
 converting them into their oxygen ethers. In the third part of 
 this investigation the affinity constants of four typical isourea 
 ethers methyl and ethyl isourea and methyl and ethyl phenyl- 
 isourea were determined by conductivity methods. The results 
 are given in the following table, together with the constants of 
 urea 4 and several other bases, for purposes of comparison. 
 
 K. 
 
 Methyl Amine io~ s x 38.00 
 
 Ethyl Isourea io~ s X 10.40 
 
 Methyl Isourea IQ- s X 6.40 
 
 Ammonia io~ s X 1.80 
 
 Ethyl Phenylisourea io~ s x 0.05 
 
 Methyl Phenylisourea io~ * X 0.02 
 
 Aniline io~ 8 X -5 
 
 Urea io- T 3 X 0.15 
 
 Guanidine is nearly as strong a base as the alkalies. Methyl 
 and ethyl isourea, as mon-acid bases, are, therefore, of about the 
 same order of strength as ammonia and the mon-alkyl amines. 
 
 1 The only exception found to the rule is that two molecules of phenylisocyanate are 
 taken up by one molecule of the isourea. 
 
 2 Bamberger: Ann. Chem. (I^iebig), 273, 277 (1893). 
 8 Stieglitz : Am. Chem.J., ai, 106. 
 
 * See page 115. 
 
In spite of the presence of two amine nitrogen atoms they behave 
 essentially as mon-acid bases. 1 They have also exceedingly small 
 affinity constants for a second molecule of acid, evidence of which 
 was shown in the conductivity measurements of the hydrochlo- 
 rides in extreme dilution (see Part III) and in the tendency of 
 these bases to form solid chlorides containing at first more than 
 one equivalent of hydrochloric acid. 2 
 
 It is noteworthy that the change of urea into methyl isourea, 
 
 NH 2 CONH 2 NH 2 C(.OCH 3 )NH 
 has increased the affinity constant of the basic molecule 4 X 10*. 
 
 EXPERIMENTAL PART. 
 
 I. . TH ACYUSOUR3AS. 
 
 The acylisoureas were obtained during this investigation by 
 two methods: First, from acyl mustard oils by the method of 
 Miquel, as improved by Lossner, Dixon, and Wheeler and John- 
 son ; 3 second, the method of Stieglitz and McKee. 3 
 
 The first method is very much the longer and more tedious, 
 requiring the four successive reactions after the preparation of 
 the mustard oils, and gives smaller yields than the second one. 
 
 By the second method the acylisoureas are very readily and 
 simply obtained by treating the isoureas with acyl chlorides and 
 potassium hydroxide. The isoureas themselves were very easily 
 accessible in any quantity by the methods of Stieglitz and Dains, 
 and Stieglitz and McKee. In some cases these have been made 
 still more rapid and convenient by modifications by Dr. R. H. 
 McKee of some of the experimental conditions originally used. 
 These modifications have not yet been published by Dr. McKee, 
 but they were kindly furnished to me by the latter while this 
 work was in progress. The first new acylisourea prepared was 
 the methyl ether of symmetrical w-nitrobenzoylphenylisourea. It 
 was prepared in the hope that the strong negative character of the 
 acyl radical would make it easy to saponify the body and in the 
 expectation that it would prove to be a solid which would serve 
 as a rapid and convenient test for the presence of methyl phenyl- 
 
 1 Vide Bredig : Ztschr. phys. Chem., 13, 289 (1894). 
 
 2 Am. Chem.J., a6, 217 (1901). 
 Loc. tit. 
 
8 
 
 isourea in oily mixtures. Only the latter expectation was ful- 
 filled. 
 
 m-Nitrobenzoylsulphocarbimide, m-NO 2 C Q H 4 CONCS f was pre- 
 pared from 25 grams dry lead sulphocyanate (about twice the 
 theoretical amount) and 12.5 grams w-nitrobenzoyl chloride in 
 the presence of dry benzene, according to the general method of 
 Dixon. 1 It was purified by fractional precipitation by petroleum 
 ether and recrystallization from the same solvent. It melts at 
 94. The analysis gave 13.58 per cent. N; calculated, 13.49 per 
 cent. 
 
 Methyl m-Nitrobenzoylthio carbonate, 
 
 m-N0 2 C.H,CONC(SH) OCH Z . 
 
 The greater part of the benzene solution of the carbimide ob- 
 tained in the last experiment was mixed with a slight excess of 
 anhydrous methyl alcohol and the mixture was uently warmed 
 on the water-bath and set aside for a few hours. Masses of light 
 yellow crystals of the appearance of velvet buttons were then ob- 
 served. These crystals were recrystallized from hot 80 per cent. 
 alcohol. The substance melted at 120. 3.5 grams of the pure 
 substance were obtained. Upon evaporation the benzene solution 
 left 4 grams of a light yellow solid, which melted at 70. This 
 was methyl w-nitrobenzoate. 
 
 Analysis of the crystals melting at 120 gave the following 
 figures: n.86 per cent. N. ; calculated for C 9 H 8 O 4 N 2 S, 11.64 
 per cent. 
 
 About 3.25 grams of the carbonate were suspended in a little 
 anhydrous methyl alcohol and the calculated amount of potassium 
 hydroxide dissolved in the minimum amount of methyl alcohol 
 was added. Thin, small scales of the potassium salt were precip- 
 itated. The salt, which is very soluble in water, was filtered off, 
 washed with absolute ether and dried on a clay plate. The yield 
 was 3 grams. Some of the salt, when heated, decomposed at 
 about 260. 
 
 Methyl Ethyl m-Nitrobenzoylimidothiocarbonate, 
 
 Three grams of the above salt were suspended in a little abso- 
 lute methyl alcohol and the calculated quantity (1.7 grams) ethyl 
 
 1 Loc. tit. 
 
iodide added. The needle-like crystals which formed over night 
 were recrystallized from methyl alcohol. The melting-point was 
 constant at 78. By evaporation another crop of the crystals was 
 obtained from the mother-liquid. The analysis gave 10.65 P er 
 cent. N. ; calculated, 10.47 P 61 " cent - 
 
 Sym-. O-Methyl m-Nitrobenzoylphenylisourea, 
 
 m-NO,C Q H,CONC (OCH Z ) NHC 6 H 5 . 
 
 This substance was prepared from the above compound and 
 aniline, according to the method of Wheeler and Johnson 1 for the 
 preparation of methyl benzoylphenylisourea. Mercaptan was 
 evolved and a dark-colored oil remained which amounted to nearly 
 the calculated quantity for the isourea. When cooled in a freez- 
 ing mixture, the oil solidified. The solid was washed with pe- 
 troleum ether, dissolved in chloroform and reprecipitated by pe- 
 troleum ether. The substance now had the form of needles, which 
 melted at 124. 
 
 The same compound was also prepared much more easily from 
 methyl phenylisourea, according to Stieglitz and McKee, as fol- 
 lows: A mixture of I gram methyl phenylisourea in 15 cc. of 
 alcohol-free ether and 0.4 gram potassium, hydroxide in 0.5 cc. 
 water was cooled to o and treated with 1 .2 grams w-nitrobenzoyl 
 chloride dissolved in a little absolute ether. A white flocculent 
 substance separated. The ether was poured off and the residue 
 extracted several times with more ether. The crystalline residue, 
 insoluble in ether, was thoroughly washed with water. The yield 
 was i gram and the melting-point 120. Precipitated from a 
 chloroform solution by petroleum ether, the substance was ob- 
 tained in the form of colorless needles, which melted at 124. 
 Some of these crystals were mixed with those obtained by the 
 method of Wheeler and Johnson, and the melting-point was un- 
 changed. The ether extracts above obtained were now examined 
 to see if they contained and isomeric methyl w-nitrobenzoylphenyl- 
 isourea, The ether was evaporated and 0.3 to 0.4 gram of a some- 
 what mucilaginous solid was left, which, after recrystallization, 
 proved to be identical with the substance already obtained, which 
 melted at 124. The latter was analyzed and gave 14.08 per cent. 
 N ; calculated, 14.07 per cent. 
 
 i Loc. cit. 
 
10 
 
 Sym. m-Nitrobenzoylphenylurea, 
 
 m-N0 2 C 6 HtCONCONHC 6 H 6 . 
 
 A small amount of the isourea was decomposed by dry hydro- 
 gen chloride at 90 to 130 and gave methyl chloride and sym. 
 w-nitrobenzoylphenylurea. The latter was purified by repeated 
 extraction with boiling alcohol or by recrystallization from a large 
 quantity of boiling alcohol. It formed very fine, colorless needles, 
 soluble in hot water, little soluble in ether and melting at 224 
 to a clear colorless liquid. The same substance also may be ob- 
 tained from the isourea by the action of warm concentrated hy- 
 drochloric acid. The analysis gave 14.88 per cent. N ; calculated, 
 14.77 P er cent - 
 
 Action of Potassium Hydroxide on Sym. O -Methyl m-Nitro- 
 benzoylphenylisourea. Very many attempts were made to saponify 
 the acylisourea in the hope of developing a new method of prepar- 
 ing isoureas. Potassium hydroxide and weaker bases (e. g., lead 
 hydroxide) were used in aqueous and alcoholic mixtures in the 
 cold and at elevated temperatures. The saponification was ob- 
 served to go with difficulty and to result in the almost total de- 
 composition of any isourea that may have been first formed. Only 
 very small quantities of the isourea were isolated. A single ex- 
 periment will illustrate the process used. 
 
 Three grams methyl w-nitrobenzoylphenylisourea were boiled 
 for one hour under a reflux condenser with 0.7 gram (i mol. +) 
 potassium hydroxide in 10 cc. water; a little more of the alkali 
 was gradually added, as the action seemed slow. Most of the sub- 
 stance finally passed into solution. The whole solution became 
 dark red in color and smelled of aniline and ammonia. Upon 
 cooling, a dark red gum separated out, but was not removed. 
 Ten grams potassium hydroxide were now added and the solu- 
 tion extracted with ether. A dark red solid remained undissolved 
 by the ether. This solid was dissolved in water and the solution 
 acidified with hydrochloric acid. A brown mucilaginous precip- 
 itate was obtained. This was washed with alcohol and gave a 
 yellow powder, which did not melt when heated to 270, but black- 
 ened. The acid solution, when cooled with ice, gave another 
 considerable precipitate, which melted sharply at 140, even when 
 mixed with m-nitrobenzoic acid. The ether was distilled from 
 the ether extract and a small amount of a reddish oil remained 
 
II 
 
 which contained some colorless crystals. The oil, when tested 
 for aniline with nitrous acid, gave a strong phenol odor and a deep 
 red oil. The remainder of the reddish oil was taken up in petro- 
 leum ether; the colorless crystals remaining melted at 147, and 
 when mixed with phenyl urea still melted at 147. The petroleum 
 ether was distilled off and the oil which was left gave, when 
 treated with dry hydrogen chloride, no methyl chloride. Hence 
 no isourea was present. A very little of the oil gave a strong 
 test for aniline with bleaching-powder. The chief products of 
 the reaction w-nitrobenzoic acid and aniline showed that com- 
 plete decomposition of the acylisourea had occurred. 
 
 Sym. O-Methyl Benzoylphenylisourea, 
 
 C Q H 5 CONC(OCH 3 )NHC Q H,. 
 
 This compound, which had been prepared both by Wheeler and 
 Johnson, and by McKee and described by them as an oil, was 
 obtained in the form of fine needles, which, when pure, melt at 
 50. 5.8 grams dimethyl benzoylimidothiocarbonate were con- 
 verted into the benzoylisourea ether by treatment with aniline, 
 according to the method of Wheeler and Johnson. The resulting 
 oil was set aside and after one day fine yellow crystals began to 
 separate in the form of needles which, in one day more, penetrated 
 the whole mass. As the quantity of these crystals did not in- 
 crease after standing several weeks, the substance was exposed 
 all day to the winter cold ( 10) and the whole mass solidified. 
 The solid was purified by cooling a concentrated methyl alcohol 
 solution of it in a freezing-mixture. The pure crystals melt at 
 50 and evolve methyl chloride almost quantitatively when treated 
 with dry hydrogen chloride. Some of the substance in petro- 
 leum ether solution was treated with hydrogen chloride and a 
 precipitate was obtained which, when purified, melted at 205, 
 the melting-point of sym. benzoylphenylurea. This proves that 
 the substance melting at 50 is symmetrical methyl benzoylphenyl- 
 isourea. 
 
 'ilie same compound was also prepared by McKee's method 
 and obtained in crystalline form. 
 
 Action of Potassium Hydroxide on O-Methyl Benzoylphenyl- 
 isourea. Six grams of the isourea were mixed with 1.4 grams 
 (i mol.) potassium hydroxide in 25 cc. water and vigorously 
 boiled under a reflux condenser for about a half hour. Some of 
 
12 
 
 the oil was then taken out and tested with hydrochloric acid. As 
 the formation of benzoylphenylurea showed that a considerable 
 quantity of the original isourea was still present, 5 cc. of alcohol 
 and i gram more of potassium hydroxide were added and the 
 boiling continued for another half hour. During the boiling a 
 strong odor of ammonia was observed. All the oil finally disap- 
 peared. After the addition of 15 grams of potassium hydroxide 
 to the cold solution a white crystalline solid separated out. This 
 was filtered off, washed with ether and dried. The amount was 
 1.5 grams. This solid was dissolved in water and the solution 
 acidified with dilute hydrochloric acid. Benzoic acid was pre- 
 cipitated (m. p. 122). The alkaline solution was extracted sev- 
 eral times with ether and then acidified with hydrochloric acid; 
 more benzoic acid was precipitated. The ether solution was dried 
 with freshly ignited sodium sulphate and the ether distilled 
 off. A thick, light yellow oil remained. When tested with con- 
 centrated hydrochloric acid the oil showed the presence of a small 
 amount of the original methyl benzoylphenylisourea. Some of 
 the residue was washed with dilute acetic acid and gave a solid, 
 which melted at 155. Some of this solid was mixed with benz- 
 anilide (m. p. 161) and the mixture still melted at 155. The 
 remainder of the oil was extracted with petroleum ether, which, 
 upon evaporation, left 1.4 grams of an oil. The oil was distilled 
 at 10-20 mm. pressure and part of the material came over at 100, 
 but nothing more distilled, although the bath was heated to 220. 
 The distillate boiled under atmospheric pressure at 183 and a 
 few drops treated with benzoyl chloride gave benzanilide (m. p, 
 161, unchanged by synthetic benzanilide). The above residue, 
 insoluble in petroleum ether, was dissolved in ether and I mol. 
 (calculated for methyl phenylisourea) of potassium hydroxide 
 in i cc. of water was added. The whole was then cooled to o 
 and i mol. -m-nitrobenzoyl chloride in absolute ether was slowly 
 added. The ether solution was then poured off and the ether was 
 evaporated. The white, gummy mass remaining was purified by 
 treating a chloroform solution of it with petroleum ether. A 
 very small amount of a substance was obtained, which melted at 
 124. The melting-point was not changed when it was mixed 
 with w-nitrobenzoylphenylisourea. It follows that the substance 
 which reacted with the w-nitrobenzoyl chloride was methyl phenyl- 
 
isourea. But it formed only a very small part of the products of 
 the reaction. It must have been formed as follows : 
 C 6 H 5 CONC(OCH 3 )NHC 6 H 5 + KOH 
 
 C 6 H 5 NHC(OCH 3 ): NH + C 6 H 5 COOK. 
 
 Many other experiments, varying all possible conditions, were 
 made on the saponification of methyl benzoylphenylisourea for 
 the purpose of improving the yield of the phenylisourea, but noth- 
 ing more than a trace was ever obtained. 
 
 It was found by Dixon that when methyl benzoylisourea was 
 boiled with a large excess of aqueous potassium hydroxide com- 
 plete saponification to benzoic acid, alcohol, carbon dioxide and 
 ammonia occurred. My results on the action of alkalies on methyl 
 benzoylphenylisourea also show complete saponification of the 
 molecule, with a destruction of the urea radical. 
 
 Silver Salt of sym. Methyl Benzoylphenylisourea, 
 C Q H 5 C(OAg) : N.C(OCH S ) : NCH 5 . 
 
 Silver nitrate (0.25 gram, a little less than I molecule) dissolved 
 in 8 cc. of 50 per cent, methyl alcohol was slowly added to a 
 mixture of methyl benzoylphenylisourea (0.4 gram dissolved in 
 10 cc. methyl alcohol) and sodium methylate (from 0.07 gram 
 sodium and 10 cc. methyl alcohol). A little silver oxide which 
 formed was filtered off and the filtrate was treated with water; 
 a white precipitate, very difficult to purify, was obtained. The 
 substance was thoroughly washed with water and ether and dried 
 on a clay plate in vacuo. A silver determination gave 30.50 per 
 cent. Ag. ; calculated for C 15 H 13 O 2 N 2 Ag, 29.92 per cent. 
 
 The silver salt, when treated with methyl chloride, gave chiefly 
 methyl benzoylphenylisourea again, no alkylation of the substance 
 being produced. The recovered benzoylphenylisourea gave methyl 
 chloride and benzoylphenylurea (m. p. 205) and formed a plat- 
 inum salt which gave 21.24 P er cent - platinum; calculated, 21.24 
 per cent. 
 
 O -Methyl Benzoylisourea Hydro chloride, 
 
 C 6 H 5 CONHC(OCH 3 )NH.HCl. 
 
 Methyl benzoylisourea (0.5 gram) was dissolved in absolute 
 ether and dry hydrogen chloride passed into the solution. The 
 precipitate was filtered off, washed with absolute ether and dried 
 in a vacuum over concentrated sulphuric acid and solid potassium 
 
hydroxide. The salt now evolved methyl chloride when heated 
 to 50. The methyl benzoylisourea itself, when treated with dry 
 hydrogen chloride without a diluent, gave off methyl chloride at 
 ordinary temperatures. Chlorine determinations of the salt freshly 
 prepared, and as dried for two days, gave 16.46 and 16.06 per 
 cent. Cl. ; calculated, 16.50 per cent. 
 
 Hence, in the course of two to three days the salt must have 
 undergone some decomposition with the loss of methyl chloride. 
 This conclusion is further confirmed by the fact that when II 
 was prepared for analysis, a slight amount of the substance 
 was found to be insoluble in water, whereas I dissolved im- 
 mediately and completely. 
 
 The Sodium Salt of O-Methyl Benzoylisourea, 
 C Q H 5 C(ONa) : N.C(OCH 3 ) : NH. 
 
 The isourea (0.5 gram) was dissolved in the least possible 
 quantity of absolute methyl alcohol and a slight excess of sodium 
 methylate, dissolved in the minimum amount of dry methyl alco- 
 hol, was added. An oil was precipitated which, after standing 
 for some time, solidified. In another experiment the oil solidified 
 at once when seeded with a little of the sodium salt. The yield 
 was quantitative. The analysis gave 1 1 .86 per cent. Na. ; calcu- 
 lated, 11.50 per cent. 
 
 As in the case of the silver salt of benzoylphenylisourea methyl 
 ether, all attempts to methylate the sodium salt led to the forma- 
 tion of the original substance, benzoylisourea. 
 
 Action of Acetyl Chloride on Methyl Phenylisourea. 
 
 Five grams methyl phenylisourea were dissolved in 25 cc. ether 
 and 2 grams ( I mol. + ) potassium hydroxide in 2 cc. water were 
 added and the mixture cooled by ice-water. The flask was then 
 removed from the cold water and 2.7 grams (i mol.) acetyl chlo- 
 ride added at once and the whole well shaken for about half an 
 hour or until all the acetyl chloride was used up. The ether solu- 
 tion was filtered off and the residue extracted several times with 
 ether, the extracts being added to the first filtrate. The ether 
 solution was dried with anhydrous sodium sulphate, filtered and 
 evaporated in vacuo. A white solid was left, mixed with a little 
 clear, colorless oil. The oil was taken up in a little petroleum 
 
15 
 
 ether, most of the solid (X) remaining. When the petroleum 
 tion washed with a little water, then with a very little dilute 
 (X) and (Y), as will be proved presently, are the isomeric methyl 
 acetylphenylisoureas. In the solid (X) the acetyl and phenyl 
 groups are attached to the same nitrogen atom, and in the oil (Y) 
 these groups are bound to different nitrogen atoms. 
 
 Sy m. O -Methyl Acetylphenylisourea, 
 
 CH 3 CONHC( :NC Q H 5 )OCH Z . 
 
 The oil ( Y) was dissolved in alcohol-free ether, the ether solu- 
 tion washed with a little water, then with a very little dilute 
 hydrochloric acid to remove any excess of methyl phenylisourea, 
 then three more times with a little water. It was finally thor- 
 oughly dried with freshly ignited sodium sulphate. Nearly all 
 the ether was evaporated and the remaining ether solution de- 
 canted from a few crystals which had separated, and the ether 
 completely evaporated. An oil was left which, when exposed all 
 day to the winter cold, showed no tendency to solidify. The com- 
 pound was identified in the following way : A small amount was 
 dissolved in absolute ether and dry hydrogen chloride passed into 
 the cold solution ; a white precipitate, which formed at once, was 
 filtered off and placed on a clay plate in vacua for two days. The 
 substance then melted at I25-I55. Washed with alcohol and 
 dried, the compound melted at 182 to a clear colorless liquid 
 and when mixed with synthetic sym. acetylphenylurea it still 
 melted at 182. Hence, the original oil (Y) was symmetrical 
 O-methyl acetylphenylisourea. The latter when treated in ether 
 solution with hydrogen chloride either reacted at once, giving 
 the corresponding urea, or else the hydrochloride was first formed 
 and then spontaneously decomposed when left in vaciw for two 
 days. Experiment showed that the former reaction takes place, 
 the methyl acetylphenylurea being formed at once from the 
 corresponding isourea. The hydrochloride itself is, under 
 these conditions, entirely unstable. Some of the oil (Y) when 
 treated with dry hydrogen chloride evolved methyl chloride when 
 heated to 60. 
 
 Two attempts further to identify the sym. methyl acetylphenyl- 
 isourea by analysis gave low results for nitrogen, which showed 
 that the substance was not obtained absolutely pure. Analytical 
 
i6 
 
 evidence identifying it completely was obtained, however, by the 
 preparation and analysis of its chlorplatinate. 
 
 Some of the oil (Y) was dissolved in absolute ether and the 
 calculated quantity of hydrochlorplatinic acid dissolved in a little 
 absolute alcohol added. A light yellow crystalline precipitate 
 formed immediately. This precipitate was washed several times 
 with absolute ether and dried for half an hour over concentrated 
 sulphuric acid and solid potassium hydroxide. It then gave 24.73 
 and 24.17 per cent. Pt; calculated for C 20 H 28 O 4 N 4 PtCl 6 , 24.54 
 per cent. 
 
 Asym, O -Methyl Acetylphenylisourea, 
 
 CH,CO(C Q H,)NC( : NH)OCH 3 . 
 
 The solid (X), recrystallized several times from boiling petro- 
 leum ether, was obtained in the form of long, beautiful, rhombic 
 prisms which melt at 102 and are very soluble in chloroform, 
 benzene, acetone and alcohol, quite easily in ether, but somewhat 
 less soluble in petroleum ether. The analysis gave 14.25 per cent. 
 N. ; calculated, 14.58 per cent. 
 
 Asym. Acetylphenylurea, CH 3 CONC 6 H 5 CONH 2 .The ether 
 (X), 0.5 gram, was treated with dry hydrogen chloride. Methyl 
 chloride, which began to form at ordinary temperature, was ob- 
 tained in quantity (35 cc.) under the influence of gentle heat, and 
 asym. acetylphenylurea was left as a white solid in the reaction 
 vessel. It was recrystallized twice from hot water and obtained in 
 the form of fine needles. These melted at 167 to a turbid liquid 
 as if on melting there had been decomposition. Mixed with sym. 
 acetylphenylurea (m. p. 183) the melting-point was depressed to 
 154. 
 
 Asym. O-M ethyl Acetylphenylisourea Hydro chloride, 
 
 CH 3 CON(C Q H 5 )C( : NH)OCH S HCI. 
 
 The asym. acylisourea, i gram, was dissolved in absolute ether 
 and dry hydrogen chloride passed into the cold solution. The 
 white precipitate was washed with absolute ether and placed in 
 vacuo over concentrated sulphuric acid and solid potassium hy- 
 droxide for forty-five minutes. A sample of the substance was 
 then dissolved in water, only a very slight turbidity appearing, 
 the solution neutralized with sodium bicarbonate and titrated with 
 
te.ith-normal sliver nitrate, which gave 15.60 per cent. Cl. ; calcu- 
 lated, 15.49 per cent. 
 
 Asym. methy acetylphenylisourea, when treated with dry hy- 
 drogen chloride, at once liquefied and evolved methyl chloride at 
 the ordinary temperature. 
 
 About 1.5 grams of the solid asym. acylisourea, not quite pure, 
 was placed in a sample tube and kept for a year and. a half. The 
 tube was then found to contain an oil, near the top of which a few 
 plate-like crystals (about o.i gram) adhered to the side of the 
 tube. The substance was placed in a freezing-mixture and cooled 
 to ( 10) for several hours, but showed no tendency to solidify 
 The plate-like crystals mentioned above were removed, powdered 
 and washed with petroleum ether. The body melted at 112, even 
 when mixed with acetanilide. No asym. acylisourea could be 
 obtained from the oil by treating it with petroleum ether accord- 
 ing to the method already pursued for the separation of the two 
 isomers. Some of the oil was now placed in a sample tube and 
 treated with dry hydrogen chloride. Methyl chloride began to be 
 evolved at a temperature of 60. The solid residue was washed 
 with petroleum ether and the melting-point was found to be 183, 
 which shows that the product was sym. acetylphenylurea. Hence 
 it is evident that the asym. O-methyl acetylphenylisourea originally 
 placed in the tube had, on being kept, passed over completely, 
 with the exception of a small amount which had decomposed, into 
 the more stable isomeric sym. O-methyl acetylphenylisourea. The 
 rearrangement can be expressed as follows : 
 
 CH 3 CONC fl H 6 .C(OCH 3 ) : NH > 
 
 HNC 6 H 5 C(OCH 3 ) : NCOCH 3 . 
 
 It was found that when the crystalline isomer is perfectly pure, 
 this transformation is much slower. Some of the pure crystals 
 when kept several months adhered to each other and the melting- 
 point had fallen only 7-io. 
 
 Action of Sodium Methy late and Silver Nitrate on Asym. 
 Methyl Acetylphenylisourea. A solution of sodium methylate 
 (from 0.06 gram sodium and 3 cc. pure methyl alcohol) was added 
 to 0.5 gram asym. methyl acetylphenylisourea (i mol.) dissolved 
 in 2.5 cc. methyl alcohol. Silver nitrate, 0.4 gram (0.8 mol.), dis- 
 solved in 5 cc. water, was gradually but rapidly added to the mix- 
 
i8 
 
 ture and this thoroughly shaken and cooled under the water tap. 
 The precipitate, which began to form at once, was at first brown, 
 but it quickly changed to a light cream color. It was immediately 
 filtered off, washed with a mixture of methyl alcohol and water 
 ( i : i ) until the washings were no longer alkaline to sensitive lit- 
 mus paper, brought on a clay plate and placed at once in a vacuum 
 desiccator over concentrated sulphuric acid and solid potassium 
 hydroxide. The yield appeared good. The filtrate when diluted 
 had a strong odor of methyl acetate. As soon as the silver salt 
 was dry, analyses were made. There was found, 41.83, 41.40 and 
 41.83 per cent. Ag. ; calculated for C 10 H 12 O 2 N 2 Ag, 41.94 per cent. 
 From the analyses it is apparent that the silver compound ob- 
 tained was not the salt of methyl acetylphenylisourea, but the silver 
 salt of methyl phenylisourea itself, the acyl group having been 
 saponified away by the treatment with sodium methylate: 
 
 CH 3 CONC 6 H 5 C( : NH)OCH 3 + NaO.CH 3 + AgNO 3 * 
 
 CH.COOCH, + AgNC(OCH 3 )NHC 6 H 5 + NaNO 3 . 
 The asym. acylphenylisoureas are therefore saponified rapidly and 
 smoothly to isoureas, in marked contrast to their symmetrical 
 isomers. 
 
 The same silver salt was now prepared directly from O-methyl 
 phenylisourea. 
 
 Silver O-Methyl Phenylisourea, AgNC(OCH s )NHC 6 H 6 or 
 HNC(OCH 3 )NAgC 6 H 5 . To a methyl alcohol solution of 0.5 
 gram methyl phenylisourea was added a solution of 0.45 
 gram (about 0.8 mol.) silver nitrate in a mixture of water and 
 methyl alcohol ( i : i ) and then to the whole was added, drop by 
 drop, with constant shaking, a concentrated sodium methylate 
 solution prepared from 0.057 gram (0.75 mol.) of sodium. The 
 pure white curdy precipitate was filtered off, thoroughly washed 
 with cold water until the washings were no longer alkaline, then 
 several times with very dilute acetic acid to remove any silver 
 oxide and finally with a little methyl alcohol. The analysis gave 
 42.08 per cent. Ag; calculated, 41.94 per cent. 
 
 This salt was also prepared in water solution as follows : To a 
 saturated aqueous solution of 0.5 gram methyl phenylisourea a 
 little less than the calculated quantity of normal sodium hydroxide 
 was added and then the whole was treated with somewhat less than 
 
UNIVEK8H 
 
 v OF 
 
 VP4 
 
 19 
 
 the theoretical amount of silver nitrate in 10 cc. of water. The 
 salt prepared by this method had a yellow color and was much 
 more difficult to purify than when prepared according to the 
 method given above. 
 
 The silver salt of methyl phenylisourea, 0.5 gram, was suspended 
 in absolute ether, the whole well cooked and a slight excess (3 
 grams) acetyl bromide added and the mixture allowed to 
 stand in the dark for several days with frequent shaking. The 
 ether solution was filtered off and evaporated in vacuo. 2.5 
 grams of an oil was left which, according to the following tests, 
 consisted largely of sym. methyl acetylphenylisourea. Some of the 
 oil was dissolved in absolute ether and treated with dry hydrogen 
 chloride. A mucilaginous precipitate was filtered off and placed 
 in vacuo over night. This precipitate, when washed with absolute 
 alcohol and dried, melted at 183. Mixed with sym. acetylphenyl- 
 urea, the melting-point was unchanged. 
 
 The formation of the sym. acetyl derivative favors the following 
 as the probable constitution of the silver salt : 
 
 AgN:C(OCH 3 )(NHC 6 H 5 ). 
 
 As a rule, the metal, in the salts of the phenyl amidines, is 
 supposed to go to the phenylamide group. 1 
 
 Silver Salt of O-Bthyl Phenylisourea, HNC Q H 5 C(OC 2 H 6 )NAg 
 or C 2 H 5 O.C(NH)NAgC 6 H 5 .To 0.5 gram ethyl phenylisourea 
 in 5 cc. absolute ethyl alcohol was added 0.5 gram (0.9 mol.) of 
 silver nitrate dissolved in a mixture of water and ethyl alcohol 
 ( i : i ) . The whole was then treated, slowly and with constant 
 shaking, with an ethyl alcohol solution of sodium ethylate pre- 
 pared from 0.06 gram (0.9 mol.) of sodium. The curdy pre- 
 cipitate was filtered off, washed, dried and analyzed, giving 39.88 
 per cent. Ag; calculated, 39.80 per cent. 
 
 Silver Salt of Sym. Methyl Acetylphenylisourea. Sym. methyl 
 acetylphenylisourea, 0.4 gram, was nearly all dissolved in about 12 
 cc. of water and 1.8 cc. (0.85 mol.) normal sodium hydroxide was 
 added and then 16 cc. (0.8 mol.) tenth-normal silver nitrate, drop 
 by drop, with shaking. The nearly white precipitate was filtered off, 
 and washed with water until the washings were only slightly alka- 
 line. An attempt was made to wash with methyl alcohol, but the 
 
 1 Bamberger : Loc. cit. 
 
20 
 
 first drop dissolved some of the precipitate and no more was added. 
 The washing was completed with ether and the salt dried in the 
 usual way. The analysis gave 35.72 per cent. Ag; calculated for 
 C 10 H 12 O 2 N 2 Ag, 36.06 per cent. 
 
 O-Methyl Acetylisourea, CH s CONC(OCH 3 )NH 2 .Methylis<>- 
 urea hydrochloride, 2 grams, and about 15 cc. absolute ether were 
 placed in a flask, 2 grams (2 mols.) potassium hydroxide in I cc. 
 water were added, the mixture shaken and the whole cooled to o. 
 Two grams (i mol.) acetic anhydride were now added and the 
 mixture shaken for some time. The ether solution was poured 
 off, the residue extracted again with ether and nearly the whole 
 of the latter allowed to evaporate in the air. The extract was then 
 placed in a vacuum desiccator for an hour or two. The substance, 
 which was at first oily, became solid. It was purified by recrystal- 
 lization from warm petroleum ether. After one recrystallization 
 the melting-point was constant at 58.5. The analysis gave 23.94 
 per cent. N. ; calculated, 24.19 per cent. 
 
 Silver Salt of O-Methyl Acetylisourea, 
 
 CH,C(OAg) : NC(OCH Z ) : NH. 
 
 Methyl acetylisourea, 1.5 grams, was dissolved in about 8 cc. 
 absolute methyl alcohol and a concentrated methyl alcohol 
 solution of sodium methylate (0.8 mol.) was added and the whole 
 treated with 1.3 grams silver nitrate. The white gelatinous pre- 
 cipitate was washed as thoroughly as possible until the washings 
 were only very slightly alkaline. The yield was good. There 
 was found, on analysis, 48.14 per cent. Ag; calculated, 48.35 per 
 cent. 
 
 O -Methyl m-Nitrobenzoylisourea, 
 
 m-N0 2 C Q H,CONC(NH 2 ) OCH 3 . 
 
 Methyl isourea hydrochloride, 3 grams, was dissolved in about 
 20 cc. water and 3 grams (2 mols.) potassium hydroxide dissolved 
 in a little water were added and then 5.1 grams (i mol.) w-nitro- 
 benzoyl chloride and the whole thoroughly shaken. A colorless 
 solid separated out. The yield was almost quantitative. The 
 substance was dissolved in benzene or in chloroform and repre- 
 cipitated by petroleum ether. In this way it was obtained in the 
 form of fine needles melting at 115. These gave 19.00 per cent. 
 N. ; calculated, 18.87 P er cent - 
 
21 
 II. CONDENSATIONS OF THE ISOUREAS. 
 
 Sym. 0-Methyl Diphenyldiureidoisourea, 
 
 C Q H 5 NHCONHC(OCH 3 ) : NCONHC 6 H 6 . 
 
 Methyl phenylisobiuret, 0.6 gram, prepared according to the 
 method of Stieglitz and McKee, was treated with 0.3 gram phenyl- 
 isocyanate, the material being kept cold. The product soon be- 
 came semi-fluid and after standing over night the contents of the 
 tube had become solid. This solid was washed a great many times 
 with ether and then melted constant at 153. It gave: C, 61.60; 
 H, 5.46. Calculated: C, 61.47; H, 5.18. 
 
 Some of the above compound was dissolved in absolute ether 
 and treated with a little dry hydrogen chloride. The precipitate 
 was filtered off, washed with absolute ether and dried as usual for 
 one and a half hours. The salt melted at 122, giving off methyl 
 chloride. A chlorine determination gave results agreeing best 
 with a sesquichloride. There was found 14.81 per cent. Cl. Cal- 
 culated for (C 16 H 16 O 3 N 4 ) 2 .3HC1, 14.48 per cent. 
 
 Carbonyl Diphenyldiurea, (C 6 H 5 NHCONH) 2 CO.$ome of 
 the diureid was placed in a sample tube and treated with dry hy- 
 drogen chloride at 60. Methyl chloride was evolved and a color- 
 less solid was left which melted sharply at 211. As the quantity 
 was small, the substance was placed in a desiccator for a day or 
 two and then analyzed without further purification. It gave: 
 C, 60.50; H, 5.20. Calculated: C, 60.34; H, 4.74. 
 
 O-M ethyl Carbethoxyisourea, C 2 H 5 OCONC ( O CH 3 ) NH 2 . 
 Methyl isourea hydrochloride, 2 grams, was treated at o, in 
 ethereal solution with potassium hydroxide (2.2 grams dissolved 
 in 1.5 cc. water) and ethyl chlorformate (1.9 gram). The dried 
 ether extracts left a colorless mobile oil, which, when it was 
 cooled in a freezing-mixture and persistently scratched, solidified 
 completely. The substance was purified by precipitation from 
 ether solution by petroleum ether. The melting-point is 5. The 
 analysis gave: C, 41.15; H, 7.21. Calculated: C, 41.05; H, 6.91. 
 
 O-M ethyl Carbethoxyisourea Hydrochloride, 
 
 C 2 H 5 OCONC(OCH S )NH 2 .HCI. 
 
 Some methyl carbethoxyisourea was dissolved in absolute ether 
 and dry hydrogen chloride passed into the solution. The precipi- 
 tate was filtered off, washed and dried as usual and analyzed 
 
22 
 
 (I, II and III) after an interval of half an hour and again (IV) 
 after a week. There was found, I, 17.72, II, 18.02, III, 19.16, 
 and IV, 15.15 per cent. Cl. Calculated, 19.40 per cent. 
 
 These results show a gradual decomposition with loss of chlo- 
 rine. The decomposition occurs as follows: 
 C 2 H 5 OCONC(OCH 3 )NH 2 .HCl-~ 
 
 CH 3 C1 + C 2 H 5 OCONHCONH 2 . 
 
 This was confirmed by the following: Some methyl carbethoxy- 
 isourea was treated with dry hydrogen chloride; at the ordinary 
 temperature, methyl chloride was evolved. The solid residue was 
 washed with water and dried; it then melted at 191 and was 
 recognized as allophanic ester. 
 
 Some of the hydrochloride, when heated, evolved methyl chlo- 
 ride in quantity at 90. 
 
 All attempts to introduce a second carbethoxyl group left the 
 body unchanged. 
 
 -Methyl Thiophenylureidoisourea, 
 
 (C 6 H 5 NHCSN:)C(OCH 3 )NH 2 . 
 
 Methyl isourea, 0.2 gram, was mixed with 0.5 gram phenyl 
 mustard oil; heat was evolved and the product soon solidified 
 when it was cooled. The substance was purified by several re- 
 crystallizations from hot benzene. Obtained thus, the compound 
 consists of diamond-shaped plates, insoluble in water and ether 
 but easily soluble in chloroform. The melting-point is 131. 
 
 The compound can also be obtained much more conveniently by 
 warming the isourea hydrochloride with phenyl mustard oil and 
 potassium hydroxide in the presence of a little water. The yield, 
 however, is much less by this method. 
 
 The substance is somewhat unstable. When kept in a desiccator 
 several days it melted at I2i-i26 and on analysis (I) gave a low 
 nitrogen content. Another sample (II) was analyzed after re- 
 maining in a vacuum only two hours. The results were 19.04 
 and 19.92 per cent. N. Calculated, 20.13 per cent. 
 
 Methyl phenylisothiobiuret was dissolved in chloroform and 
 dry hydrogen chloride added. The white crystalline precipitate 
 was dried and when heated to 115 melted with evolution of 
 methyl chloride. 
 
 Methyl phenylisothiobiuret, when treated with dry hydrogen 
 chloride and heated to 75-9O, gave off methyl chloride. The 
 
23 
 
 solid phenylthiobiuret remaining in the tube was recrystallizcd 
 from absolute alcohol and obtained in the form of very fine 
 needles, which melted at 171 with decomposition, a gas being 
 evolved having an odor similar to that of mercaptan. 
 
 While methyl isourea condenses with 2 molecules of phenyliso- 
 cyanate, it reacts only with I molecule of phenyl mustard oil. 
 
 O-M ethyl Isobiuret, H 2 NCON :C(OCH 3 )NH 2 . One gram 
 methyl isourea hydrochloride was dissolved in 4 cc. water and 
 added to a solution of 0.08 gram potassium isocyanate in 4 cc. 
 water and the mixture allowed to evaporate to dryness in a warm 
 place. The residue was extracted repeatedly with boiling benzene. 
 The benzene solution was evaporated and 0.2 gram of a solid was 
 obtained which melted at 110. Some of this solid, when treated 
 with dry hydrogen chloride, began to evolve methyl chloride at the 
 room temperature and left a product which, thoroughly washed 
 with water and dried, melted at 190 the melting-point of 
 biuret. It also gave the biuret reaction with copper sulphate and 
 sodium hydroxide. Methyl isobiuret, when purified by recrystal- 
 lization from hot benzene, melted at 118. 
 
 The analysis gave : C, 30.98 ; H, 6.30. Calculated : C, 30.72 ; H, 
 6.03. 
 
 Benzylidene Dimethyldiisourea, 
 
 C Q H 5 CH:(NHC(OCH 3 ) :NH) 2 . 
 
 Methyl isourea, 0.72 gram, was added to I gram (a mol.) benz- 
 aldehyde. Nearly all the methyl isourea dissolved in a few minutes 
 without heat evolution. After standing for about two days, the sub- 
 stance was almost completely solid. This solid, insoluble in ether, 
 acetone and chloroform but soluble in methyl alcohol, was washed 
 many times with absolute ether. It then melted constant at 137. 
 The ether washings were treated with dry hydrogen chloride and 
 allowed to stand and a small amount of a crystalline substance 
 separated which melted at 235. Tribenzotetraureid melts at 
 240. 
 
 The substance melting at 137 was analyzed and gave: C, 
 55.33 ; H, 6.81. Calculated : C, 55.85 ; H, 6.84. 
 
 It is evident from the above that 2 molecules of methyl isourea 
 reacted with one of the benzaldehyde as follows : 
 
 2H 2 NC(OCH 3 ) : NH + C 6 H 5 CHO 
 
 C,H 5 CH : [NHC(OCH 3 ) : NH] 2 + H 2 O. 
 
24 
 
 Small quantities of a tribenzylidene tetraisourea were formed 
 at the same time. 
 
 Some of the diisourea when treated with dry hydrogen chloride 
 evolved methyl chloride at the room temperature. The residue, 
 benzylidene diureid, was washed with ether and acetone and began 
 to decompose when heated to 195 -200 and melted at 210, 
 giving off a little gas. Schiff 1 gives the melting-point of his 
 benzodiureid as 195 and adds that heated higher it decomposed. 
 Richter gives the melting-point 200. 
 
 The following experiment was made in the attempt to obtain 
 the hydrochloride. The isodiure'id was dissolved in absolute 
 methyl alcohol and dry hydrogen chloride slowly passed into the 
 cold solution. A precipitate, obtained by the addition of ether, 
 was filtered off, washed and dried as usual for two hours. 
 
 It then melted at 85, giving off methyl chloride. It gave, by 
 titration, 19.37 P er cent - Cl. Calculated for C n H 16 O 2 N 4 .2HCl, 
 22.91 per cent. 
 
 Benzylidene Diethyldiisourea, 
 
 C Q H 5 CH: [NHC(OC 2 H 5 ):NH] 2 . 
 
 Ethyl isourea, 0.7 gram, dissolved in a little absolute ether, was 
 mixed with 0.84 gram (i mol.) redistilled benzaldehyde. After 
 standing two weeks, a white crystalline mass was obtained which 
 was thoroughly washed many times with absolute ether and finally 
 with a little acetone. The substance then melted at 154 and was 
 insoluble in water, ether and alkalies and nearly insoluble in ben- 
 zene, but soluble in chloroform, acetone and in dilute acids. No 
 definite crystalline form could be observed under the microscope. 
 
 The analysis gave: C, 59.19; H, 7.51. Calculated: C, 59.01; 
 H, 7.64. 
 
 An impure hydrochloride of the isodiureid was obtained by 
 treating a chloroform solution of the ureid with dry hydrogen 
 chloride. When heated, this salt melted and gave off ethyl chlo- 
 ride at 90. The chloride was allowed to stand in the air in a 
 warm place for several hours. The melting-point was then found 
 to be 195 the melting-point of benzodiureid. Evidently com- 
 plete decomposition had occurred. 
 
 Some ethyl isourea and benzaldehyde were mixed in equimolec- 
 ular quantities and the mixture allowed to stand for several 
 
 i Ann. Chem. (Uebig), 151. J 92 (1869). 
 
25 
 
 months. The product was then washed with ether and treated 
 with dry hydrogen chloride. Ethyl chloride was evolved and a 
 solid residue remained which, when purified, melted at 240 with 
 decomposition. This is the melting-point tribenzylidene tetra- 
 ureid. Evidently the substance formed by the long-continued 
 action of benzaldehyde was a much higher condensation product 
 than that first obtained. This substance, as is shown by its de- 
 composition product, tribenzylidene tetraureid, was tribenzylidene 
 tetrethyl isotetraure'id. 
 
 By condensation of isourea ethers with /3-keto-acid esters the 
 oxygen ethers of ju -oxypyrimidines were easily obtained. Their 
 ready formation by this method promises to be serviceable in syn- 
 thetic work in the uric acid series. 1 
 
 IJL-Methoxy-a-methyl-y-oxypyrimidine, 
 
 N: C(OCH^N: C(CH,}CH: C OH. 
 
 A mixture of 0.5 gram methyl isourea and 0.8 gram (i mol.) 
 acetoacetic ether formed a light yellow oil which, after standing 
 a day or two^or upon being warmed on the water-bath to 50 
 for a few minutes, almost completely solidified. The product 
 was thoroughly washed with ether and crystallized from boiling 
 alcohol in feathery masses of needles which melted constantly at 
 207 after several recrystallizations. The yield was about 90 per 
 cent, of the theoretical. The pyrimidine is insoluble in the or- 
 dinary organic solvents in the cold, readily soluble in boiling ben- 
 zene or alcohol, as well as in dilute acids or alkalies. 
 
 The analysis gave: C, 51.26; H, 5.93. Calculated: C, 51.37; 
 
 H, 576. 
 
 The reaction between methyl isourea and acetoacetic ether is 
 analogous to that between the amidines and acetoacetic ether, 2 and 
 may be given as follows : 
 CH 3 OC( : NH)NH 2 + CH 3 C(OH) : CHCOOC 2 H 5 -> 
 
 N :C(OCH 3 )N : C(CH 3 )CH : C(OH) + C 2 H 6 O + H 2 O 
 I I 
 
 The splitting off of both alcohol and water seems to be simul- 
 taneous, as no indications of any intermediate products were ever 
 found. 
 A little of the oxypyrimidine was dissolved in the minimum 
 
 1 Mr. R. W. Noble is carrying out work along this line in this laboratory. J. S. 
 
 2 pinner: " Imidoather," p. 216. 
 
26 
 
 amount of ethyl alcohol and treated with a slight excess of hydro- 
 chlorplatinic acid, also in concentrated solution. Absolute ether 
 was now added and an oil was precipitated, which soon crystal- 
 lized in the form of yellow spindle-shaped needles. The crystals 
 were dried for half an hour, and then gave 28.33 P er cent - Pt. 
 Calculated for (C 6 H 8 O 2 N 2 ) 2 H 2 PtCl 6 , 28.24 per cent. 
 
 A small amount of the oxypyrimidine was dissolved in dry 
 benzene and treated with dry hydrogen chloride. The precipitate 
 was dried in vacuo over solid potassium hydroxide for half an 
 hour. 
 
 Some of the hydrochloride evolved methyl chloride when heated 
 to 90 -i 00. The solid residue began to decompose when heated 
 to 270, proving it to be methyl uracil formed according to 
 
 HC1, N : C(OCH 3 )N : C(CH 3 )CH : COH 
 
 I i 
 
 HN, CO.N : C(CH 3 )CH : COH + CH 3 C1 
 
 By titration there was found 20.03 P er cent - Cl. Calculated, 
 20.06 per cent. 
 
 The silver salt was obtained from 0.2 gram of the oxypyr- 
 imidine dissolved in absolute methyl alcohol, by the addition of 
 a methyl alcohol solution of sodium methylate (prepared from 
 the calculated amount of sodium) and then of the equivalent 
 amount of silver nitrate in a mixture of methyl alcohol and water 
 ( i : i ) . A very thick gelatinous precipitate formed which it was 
 impossible to wash even with the pump. It was placed on a clay 
 plate in vacuo for several days until it was perfectly dry, then 
 finely powdered and washed repeatedly with water, methyl alcohol 
 and ether, and dried as before. It thus gave 43.36 per cent. Ag. 
 Calculated for C 6 H 7 O 2 N 2 Ag, 43.65 per cent. 
 
 p-Ethoxy- a-methyl- y-oxypyrimidine, 
 
 N: C(OC,H,).N: C(CH Z )CH : COH 
 
 Ethyl isourea, 2 grams, was mixed with 3 grams (i mol.) aceto- 
 acetic ether. The mixture, warmed at 60 for one hour, almost 
 completely solidified. This solid, when washed with absolute 
 ether and recrystallized from boiling absolute alcohol, was ob- 
 tained in the form of fine shining needles, which melted at 206. 
 These gave : C, 54.43 ; H, 6.73. Calculated : C, 54.48 ; H, 6.55. 
 
27 
 
 The chlorplatinate was prepared by the method described above 
 for the corresponding methyl derivative. The crystals were yel- 
 low needles, which gave 26.95 per cent. Pt. Calculated, 27.14 
 per cent. 
 
 A small amount of the oxypyrimidine in concentrated benzene 
 solution was treated with a little dry hydrogen chloride. The 
 precipitate was washed with dry benzene and dried for forty 
 minutes (I) and eighteen hours (II), respectively. By titra- 
 tion these gave, 1749 and 17.78 per cent. Cl. Calculated for 
 C 7 H 10 O 2 N 2 HC1, 18.59 per cent. 
 
 Some of the oxypyrimidine was heated in a stream of dry 
 hydrogen chloride and evolved ethyl chloride at 9O-I3O. The 
 solid residue decomposed when heated to 270. It was methyl 
 uracil. 
 
 fJi-Methoxy- a-methyl-$-ethyl- y '-oxypyrimidine, 
 
 N: C( OCH,} .N: C. ( C7/ 3 ) . C( C,// 6 ) C OH. 
 
 Methyl isourea, 0.6 gram, was mixed with 1.2 grams (i mol.) 
 ethyl acetoacetic ether. The mixture formed a clear oil which 
 on standing over night became filled with four-sided needles in 
 masses from a common center. The crystals were washed with 
 absolute ether and after several recrystallizations from hot abso- 
 lute alcohol melted constant at 210. 
 
 The compound is easily soluble in acid or alkali. The analysis 
 gave: C, 56.94; H, 7.43. Calculated: C, 57.07; H, 7.20. 
 
 An attempt was made to prepare the hydrochloride from the 
 oxypyrimidine in benzene or chloroform solution and dry hydrogen 
 chloride, but the product was always mucilaginous and not easily 
 purified. However, the salt was easily obtained from a solution 
 of 0.3 gram oxypyrimidine in the calculated amount of hexanor- 
 mal hydrochloric acid, by evaporation in vacuo. After standing 
 in vacuo nearly a day the dry salt was analyzed, and gave 17.12 per 
 cent. Cl. Calculated for C 8 H 13 O 2 N 2 C1, 17.31 per cent. 
 
 O-M ethyl Oxdylisourea, ( p-M ethyl Parabanic Acid), 
 
 NH. C( OCH^ : N. CO. CO. 
 
 i I 
 
 Methyl isourea, 0.4 gram, was mixed with a slight excess (i 
 gram) oxalic ester. In a few minutes the whole mass apparently 
 became solid. After standing for several days, the compound 
 
28 
 
 was washed repeatedly with ether, benzene and petroleum ether 
 and then recrystallized from absolute alcohol. It was obtained 
 in the form of three-sided prisms, which melt at 137.5. Th e 
 crystals are insoluble in ordinary organic solvents, but easily 
 soluble in water, alkali and boiling alcohol. 
 
 The chlorplatinate of this substance was prepared and analyzed 
 as follows: A small amount of the compound was dissolved in 
 absolute alcohol and about the calculated quantity of hydrochlor- 
 platinic acid, also in absolute alcohol, was added. Upon the ad- 
 dition of dry benzene, a bright yellow solid separated. 
 
 This gave 29.60 per cenr. Pt. Calculated for C 8 H 10 O 6 N 4 PtCl , 
 29.71 per cent. 
 
 The reaction by which methyl oxalylisourea is formed may be 
 given as follows : 
 
 CH 3 OC( : NH)NH 2 + (COOC 2 H 5 ) 2 ~ 
 
 CH 3 OC : N.CO.CONH -f- 2C 2 H 6 O 
 
 [ i 
 
 Some of the compound, when treated with a little dilute hydro- 
 chloric acid, dissolved completely at first and then almost imme- 
 diately deposited a solid. This solid, dried in vacuo, was gently 
 heated, dissolved in alcohol and reprecipitated by petroleum ether. 
 The substance thus obtained began to decompose when heated 
 to 190. It was undoubtedly oxalylurea. 
 
 in. THE AFFINITY CONSTANTS OF ISOUREAS. 
 For an isourea which is ionized according to 4 
 
 HN : C(OR)NH 2 , H 2 COHN : C(OR)NH 3 + OH, 
 and which does not belong to the class of strongest bases, 1 such 
 as the alkalies, we would have the affinity constant, K, expressed 
 in the following equation: 
 
 CoHXCp = KXC M . (i) 
 
 COH and C P are the concentrations of the hydroxyl ions and 
 the positive base ions in terms of gram ions per liter and C is 
 the concentration of the non-ionized amine. 
 
 The affinity constants of the most important representatives of 
 
 1 For the strongest bases, as is well known, equation (\) does not hold good. Vide 
 Rudolphi : Ztschr. phys. Chem., 17, 385; Van't Hoff: Ibid., 18, 301 ; Kohlrausch : Ibid., 18, 
 661. The isomers, as will be shown below, give good constants according to (i) and be- 
 long, therefore, to the so-called class of "half electrolytes." (Van't Hoff: "Theoretical 
 and Physical Chemistry," I, p. 117.) 
 
29 
 
 the typical classes of isoureas, H 2 NC(OR):NH, and (alphyl) 
 HNC(OR) : NH, were determined by the conductivity method 
 as developed by Ostwald, 1 and van't HofP and as applied espe- 
 cially by Bredig 3 to the measurement of the affinity constants of 
 bases. The proportion (or) of the base ionized in a given solu- 
 tion was ascertained from the molecular conductivity of the solu- 
 tion from the relation 
 
 in which A*> expresses the molecular conductivity of the base 
 when i gram-molecule is dissolved in v cc. water, and A w * s the 
 extreme molecular conductivity. 
 
 Then if we express by A the number of liters 4 containing I 
 gram-molecule of the amine, equation (I) resolves itself into 
 
 (3)' 
 
 The molecular conductivities A of the bases were determined 
 by conductivity measurements made with solutions of the free 
 bases. The Kohlrausch apparatus was used and the measure- 
 ments made at a temperature of 25 (0.01). The molecular 
 conductivities of the bases in the extreme dilution, A,I were 
 ascertained in the usual way by a determination of the extreme 
 molecular conductivity, A'OO> f the hydrochlorides of the bases 
 and by calculation of A*, according to the well-known equation, 
 Aoo A'OO 4>ci + 4>OH (4) 
 
 in which AOO an d A'OO are the extreme molecular conductivities 
 of the free bases and the hydrochlorides respectively and /^QH 
 and /ooci represent the extreme mobility of the hydroxyl and the 
 chlorine ions. /^OH was taken as I95.8, 6 /,ci as 75. 9, 7 both in 
 
 1 Ztschr. phys. Chem., 2, 36, 270 (1888). 
 
 2 Ibid., 2, 781 (1888). 
 a Ibid., 13, 289 (1893). 
 
 * The conductivity measurements are given in this paper in reciprocal ohms, and all 
 the units used in the measurements are those given in Kohlrausch and Holborn's 
 " I<eitverm6gen der Blektrolyte," the unit of concentration being the gram-molecule (or 
 equivalent) in i cc. The affinity constants, however, are given, in accordance with the 
 more general usage, in terms of the unit of concentration of i gram-molecule per liter. 
 
 5 Ostwald : Ztschr. phys. Chem., 2, 278 (1889). 
 
 6 Kohlrausch (Loc. cit., p. 200) gives for /^OH at 18 the value 174 in reciprocal ohms. 
 Its value at 25 was calculated with the aid of the temperature coefficient (a) for hydroxyl 
 ions as determined by I<oeb and Nernst (Ztschr. phys. Chem., 2, 963). a = 0.0159 and 
 
 is = 4s !>+(< 25)]- 
 
 7 Kohlrausch (Loc. cit.) gives for the extreme mobility of chlorine ions at 18 the value 
 65.9. The temperature coefficient for these ions is 0.022 of the value found at 18 (Arrhe- 
 nius : " Electrochemistry," p. 142). 
 
30 
 
 reciprocal ohms, for 25. By combining (2), (3) and (4) the 
 constants, K, were calculated on the basis of the experimental 
 determinations made. The results obtained with the various bases 
 follow : 
 
 Methyl Isourea, HN :C(OCH 3 )NH 2 . Methyl isourea chloride, 
 prepared according to the method of Stieglitz and McKee, 1 and 
 recrystallized twice from boiling absolute methyl alcohol, washed 
 with absolute ether and placed in vacuo over solid potassium hy- 
 droxide and concentrated sulphuric acid for three days. A solu- 
 tion of some of this salt in water reacted neutral to sensitive litmus 
 paper. An analysis gave 32.22 per cent. Cl. Calculated for 
 C 2 H 6 ON 2 .HC1, 32.04. 
 
 The conductirity measurements with this salt are given in 
 Table I, in which v is the volume in liters, containing a gram- 
 molecule of the salt, A the molecular conductivity at 25 in re- 
 ciprocal ohms, at the concentration in question. A'> > the extreme 
 molecular conductivity of the salt, is found according to Ost- 
 wald's 2 and Bredig's 3 empirical law from each molecular conduc- 
 tivity, Av by adding values, 4 d v , which are characteristic for the 
 differences A, At/, and which are approximately constant for 
 salts in general. 
 
 TABI,E I. 
 
 v. A. A'o,- 
 
 i. n. i. ii. 
 
 32 104.06 104.04 119.1 119.0 
 
 64 107.97 107.97 119.7 119.7 
 
 128 111.30 110.98 IJ 9-9 119.6 
 
 256 US-IS 113-05 II9-55 II9-7 
 
 512 U5.87 H5.5I 120.2 119.8 
 
 1024 [120.12] [118.17] [ I2 3-3] [121.4] 
 
 Means (excluding v= 1024): 119.7 119.6 
 
 In taking the mean value for A'*,* the value found when 
 v = 1024, was excluded because of the obvious fact that at that 
 dilution some irregularity manifests itself. The irregularity is 
 either due to a slight hydrolysis or, much more likely, to the fact 
 
 1 Loc. cit. 
 
 2 " L,ehrbuch d. Allgem. Chemie," Vol. II, 693. 
 8 Ztschr. phys. Chem., 13, 198. 
 
 4 Bredig's values for dv were used, multiplied by the factor i. 066 to convert the re- 
 ciprocal Siemens' units into reciprocal ohms (see Kohlrausch : Loc. cit., p. 144, for the 
 use of the factor 1.066 in place of 1.063, the international factor). 
 
lliat at that dilution methyl isourea begins to act perceptibly as a 
 diacid base. 1 
 
 The agreement between the values for A ' in each series and 
 
 A\. 00 
 
 between the means for each series is very satisfactory. This 
 fact shows that, except possibly in very high dilutions (when 
 v = 1024) and probably not even then, there is no hydrolysis of 
 the salt of any moment. Even the most dilute solutions were per- 
 fectly neutral to sensitive litmus paper and litmus solution. 
 
 Since ^01=75.9 at 25 we have / ooP = 119.7 75-9 = 43-8. 
 That is, the extreme mobility of the positive ion of methyl isourea 
 is 43-8. 
 
 The molecular conductivity of the free base in extreme dilu- 
 tion, A oo> i s found from equation (4). 
 
 A*, = /OOP + /OOOH = 43-8 + 195-8 = 239.6. 
 
 A sample of the free base was prepared according to the 
 method of Stieglitz and McKee, 2 and dried next to solid potas- 
 sium hydroxide for several hours. Its purity was ascertained by 
 titration against tenth-normal hydrochloric acid (with methyl 
 orange as indicator). 3 
 
 0.0939 gram required 12.68 cc. tenth-normal HC1. Calculated, 
 12.66 cc. 
 
 The conductivity measurements for the free base at 25 are 
 given in Table II, in which v and A*/ have the same meanings as 
 in Table I. In the third column the values for a are given as 
 calculated according to equation (2), and in the last column 
 
 TABLE II. 
 
 V, 
 
 Az>. 
 
 looa. io 6 K. 
 
 
 i. 
 
 n. 
 
 I. 
 
 ii. 
 
 i. 
 
 ii. 
 
 C 
 
 10.61 
 14.60 
 
 10.57 
 14.59 
 
 4-43 
 6. 10 
 
 4-42 
 6.10 
 
 6.4 
 6.4 
 
 6.4 
 
 6.2 
 
 128 
 
 20.30 
 
 20.22 
 
 8.48 
 
 8-45 
 
 6.1 
 
 6,1 
 
 256 
 
 27-73 
 
 27.57 
 
 11-55 
 
 11.52 
 
 5-9 
 
 5-9 
 
 5" 
 
 37-93 
 
 37-02 
 
 15-85 
 
 15-47 
 
 5-8 
 
 5-5 
 
 1024 
 
 51-74 
 
 49-35 
 
 21.62 
 
 20.62 
 
 5-9 
 
 5-2 
 
 Means : 6.08 5.90 
 
 1 Vide, Bredig : Loc. ctt., p. 122. For the case in question, the correctness of this 
 latter view is demonstrated by the fact that the weaker bases of the series, the phenyl- 
 isoureas, do not show any anomaly ; their salts would be much more likely to suffer hy- 
 drolysis than the salts of the unsubstituted isoureas, but they would be much less likely 
 to behave as diacid bases. Their normal behavior is good evidence, therefore, that the 
 irregularity in the case of methyl and ethyl isourea when v is 1024 is due to the partial 
 ionization of the latter as diacid bases. 
 
 Loc. ctt. 
 
 Stieglitz and McKee : Loc. cit. 
 
32 
 
 the values for the affinity constant, K, are given as determined 
 from equation (3). 
 
 For comparison, the affinity constant of urea was calculated 
 from the data given by Walker 1 on the hydrolysis of solutions 
 of urea hydrochloride containing varying proportions of the acid 
 and base. The constant, K, was derived according to Walker's 
 formula 
 
 Salt ^ 
 Acid X Base 
 
 in which salt, acid and base represent the concentrations of the 
 substances in gram-molecules per liter. The average constant 
 was found to be 1.28 (0.06). This constant, according to 
 Arrhenius 2 is the constant ratio between the affinity constant of 
 the base and the dissociation constant of water which is 
 i.2X io~~ 14 . We find thus the affinity constant 3 of urea to be 
 1.28 X 1.2 X io~ 14 or 1.54 X io~ 14 . Urea is then but little 
 stronger as a base than water namely, about sixty times as 
 strong. 4 The simplest isourea, methyl isourea, whose affinity con- 
 stant, as just determined, is 6.4 X io~5 , is, therefore, 4 X io 9 
 as strong a base as the parent substance, urea. 
 
 It is a base whose affinity is of the order of that of ammonia r> 
 (K NH4 oH = i.8X io-5). 
 
 Guanidine, the amide corresponding to the isourea ethers, is 
 a very much stronger base, standing much closer to the alkalies 
 than to the amines. 6 
 
 Ethyl Isourea, NH 2 C(OC 2 H 5 ) :NH. Ethyl isourea hydrochlo- 
 ride was recrystallized twice from boiling absolute alcohol. An 
 aqueous solution of the salt was neutral to sensitive litmus paper. 
 The salt was dried for three days over concentrated sulphuric 
 acid and solid potassium hydroxide, and its purity tested by a 
 titration against tenth-normal silver nitrate, which gave 28.61 per 
 cent. Cl. Calculated for C 3 H 8 ON 2 .HC1, 28.43 per cent. 
 
 1 Ztschr.phys. Chem., 4, 326 (1891) and Ber. d. chem. Ges., 34, 4117 (1901). 
 
 2 Ztschr.phys. Chem., 5, 17 (1892). 
 
 3 Walker (/. Chem. Soc. (Condon) 83, (1903)), since this was written, has calculated the 
 affinity constant of urea on the basis of a new set of more careful experiments and found 
 K = 1.5 X io *< . This value is so near the one calculated in the text that we have let the 
 latter stand. 
 
 * The affinity constant of water. K = CH C g O H is one fifty-fifth of its dissociation 
 
 constant, K = CH X COH. 
 
 & Bredig: Ztschr.phys. Chem., 13, 294, and foot-note p. 293 (1893). 
 Ostwald : J. prakt. Chem., 33, 367. 
 
33 
 
 The conductivity measurements made with this salt at 25 are 
 given in Table III. 
 
 TABUS III. 
 
 Af. AOO- 
 
 v. I- II. I. II. 
 
 32 99-Jo 99.24 114.1 114.2 
 
 64 102.72 103.19 114.5 ii5-o 
 
 128 106.59 106.71 115.2 115.3 
 
 256 107.60 107.60 114.0 114.0 
 
 512 III. 20 110.33 II5-5 II4.6 
 
 1024 [114.28] [114.17] [117.5] [117.4] 
 
 Means (excluding v = 1024): 114.7 114.6 
 
 t<*P= II4-7 75.9 = 38.8. 
 
 The extreme molecular conductivity of the free base A> is 
 the sum of 38.8 and 195.8 (the extreme mobility of hydroxl ions), 
 or 234.6. 
 
 The free base obtained according to the method of Stieglitz and 
 McKee was tested for purity with the following result : 
 
 0.0902 gram substance required 10.15 cc. tenth-normal HC1. 
 Calculated, 10.23 cc - 
 
 The conductivity measurements and the calculation of the affin- 
 ity constant, K, follow : 
 
 
 
 1 
 
 'ABLE IV. 
 
 
 
 
 A. looa. 
 
 I0 5 
 
 K. 
 
 V. 
 
 I. 
 
 ii. 
 
 i. 
 
 II. 
 
 I. 
 
 II. 
 
 8 
 
 6.73 
 
 6.70 
 
 2.87 
 
 2.86 
 
 10.6 
 
 10.5 
 
 16 
 
 9.58 
 
 9.41 
 
 4.09 
 
 4.02 
 
 10.9 
 
 10.5 
 
 32 
 
 1341 
 
 13.18 
 
 5-72 
 
 5-63 
 
 10.9 
 
 10.5 
 
 64 
 
 18.74 
 
 18.37 
 
 8.00 
 
 7.84 
 
 10.9 
 
 10.4 
 
 128 
 
 25.9 1 
 
 25.34 
 
 1 1. 06 
 
 10.80 
 
 10.8 
 
 10.0 
 
 256 
 
 35.56 
 
 34.30 
 
 15-18 
 
 14.64 
 
 10.6 
 
 10.0 
 
 Means : 10.8 10.3 
 
 Ethyl isourea is, therefore, nearly twice as strong a base as 
 methyl isourea. It is interesting to observe that the substitution 
 of an ethyl for a methyl group attached to oxygen has caused a 
 much more decided increase in the affinity constant than is the 
 case when a similar single substitution is effected for a methyl 
 group attached to nitrogen (the constants for methyl and ethyl 
 amine are 0.00x350 and 0.00056 respectively). 
 
 Methyl Phenylisourea, C 6 H.NHC(OCH B ) : NH. Pure redis- 
 tilled methyl phenylisourea was dissolved in absolute ether and 
 
34 
 
 a slight excess of dry hydrogen chloride added. The salt was 
 washed with absolute ether and dried in vacuo over concentrated 
 sulphuric acid and solid potassium hydroxide for several days. 
 Its water solution was then neutral to sensitive litmus paper. The 
 analysis gave 18.90 per cent. Cl. Calculated, 18.99 P er cent - 
 
 The conductivity measurements made with this salt at 25 
 are given in Table V. 
 
 TABUS V. 
 
 
 
 A". 
 
 
 
 Aoo- 
 
 
 V. 
 
 I. 
 
 II 
 
 III. 
 
 I. 
 
 II. 
 
 in. 
 
 32 
 
 90.36 
 
 90-33 
 
 89.79 
 
 105.4 
 
 105.3 
 
 105.8 
 
 64 
 
 94-49 
 
 94-35 
 
 94.66 
 
 106.3 
 
 106.1 
 
 106.5 
 
 128 
 
 96.85 
 
 96.85 
 
 96.64 
 
 105.5 
 
 105.4 
 
 105.2 
 
 256 
 
 98.87 
 
 98.82 
 
 98.79 
 
 105-3 
 
 105.2 
 
 105.2 
 
 512 101.07 101.22 100.97 105.4 105.5 105.3 
 
 1024 102.55 102.67 102.40 105 7 1 105.8 105.6 
 
 Means : 105.6 105.6 105.6 
 
 4,p= 105.6 75-9 = 29.7. 
 
 The extreme molecular conductivity of the free base, A W i- s 
 the sum of 29.7 and 195.8 (the extreme mobility of hydroxyl 
 ions), or 225.5. 
 
 For the measurements of the conductivities of the free methyl 
 phenylisourea, the latter was purified by two redistillations. The 
 base, after it was dried for two days in vacuo, gave the following 
 test for purity : 
 
 0.2627 gram substance required 17.54 cc. tenth-normal HC1. 
 Calculated, 17.49 cc. 
 
 The measurements and the calculation of the affinity constant, 
 K, follow : 
 
 TABT.E VI. 
 
 At'. 
 
 iooa. 10 K. 
 
 V. 
 
 I. 
 
 II. 
 
 I. 
 
 n. 
 
 I. 
 
 II. 
 
 8 
 
 0.307 
 
 0.31 
 
 0.136 
 
 0.138 
 
 0.022 
 
 0.024 
 
 16 
 
 0.440 
 
 0.445 
 
 0.195 
 
 0.198 
 
 0.024 
 
 0.024 
 
 32 
 
 0.627 
 
 0.634 
 
 0.278 
 
 0.282 
 
 0.024 
 
 0.025 
 
 64 
 
 0.909 
 
 0.905 
 
 0.404 
 
 0.402 
 
 0.026 
 
 0.025 
 
 128 
 
 I-33I 
 
 I-33I 
 
 o.59i 
 
 Q.59 1 
 
 O.O27 
 
 0.027 
 
 256 
 
 2.056 
 
 2.017 
 
 0.913 
 
 0.896 
 
 0.026 
 
 O.O32 
 
 Means : 0.025 0.026 
 The affinity constant of methyl phenylisourea is, therefore, only 
 
 1 It is noteworthy, but not unexpected, that in this case there is no abnormal 
 increase of the molecular conductivity (see foot-note p. 459). 
 
35 
 
 one-three hundredth that of methyl isourea. It is five hundred 
 times greater than that of aniline 1 (K 5 X io~ 10 ). The de- 
 terminations show that it is not sensibly 2 hydrolyzed in dilute 
 solution and the neutrality to sensitive litmus paper and litmus 
 solution confirms this view. 
 
 Ethyl Phenylisourea, C 6 H 5 NHC(OC 2 H 5 ) :##. Ethyl phenyl- 
 isourea hydrochloride was prepared in exactly the same way as 
 the methyl derivative. A water solution of the salt was neutral to 
 sensitive litmus and a chlorine determination gave 17.76 per cent. 
 Cl. Calculated, 17.57 per cent. 
 
 Table VII gives the conductivity measurements made with the 
 salt at 25. 
 
 TABUS VII. 
 A.V. Aoc 
 
 V. I. II. I. II. 
 
 32 88.70 89.38 103.7 104.4 
 
 64 92.86 92.86 104.8 104.7 
 
 128 95.90 95.90 104.5 104.5 
 
 256 97.51 97.51 103.9 103.9 
 
 512 99.67 100.15 104.0 104.4 
 
 1024 101.43 101.44 104.6 104.6 
 
 Means: 104.1 104.6 
 
 1 XP = 104.3 75.9 = 28.4. 
 
 The extreme molecular conductivity of the free base, Aoo * s 
 the sum of 28.4 and 195.8 (the extreme mobility of hydroxy! 
 ions), or 224.2. 
 
 Ethyl phenylisourea was prepared, purified, and tested for 
 purity exactly as the methyl derivative. 
 
 0.4806 gram substance required 29.30 cc. tenth-normal HC1. 
 Calculated, 29.27 cc. 
 
 The measurements and the calculation of the affinity constant, 
 
 K, follow : 
 
 TABUJ VIII. 
 \ v looor. io 5 K. 
 
 t/.s I. ' II. I. II. I. II. 
 
 26.03 0.822 0.822 0.367 0.367 0.052 0.052 
 
 52.07 1.118 1.108 0.499 -498 0.048 0.048 
 
 104.13 1.580 1.571 0.705 0.701 0.048 0.048 
 
 208.26 2.314 2.285 1.032 1.019 0.052 0.050 
 
 416.53 3-469 3-383 1.548 1.510 0.058 0.056 
 
 833.06 5.406 5.253 2.412 2.344 
 
 Mean : 0.051 ; 0.051 
 1 Bredig : Loc. '/., p. 322. 
 
 * Within the limits of the sensitiveness of the measurements. 
 
 3 An error was made in calculating the amount of the base necessary for a N/32 solu- 
 tion. The volumes, v, given are those actually used. 
 
36 
 
 Here again the substitution of the ethyl for the methyl group 
 doubles the strength of the base. 
 
 For his interest, constant aid and advice, I wish here to express 
 my great sense of obligation and gratitude to Professor Stieglitz. 
 
 OF THI 
 
 1 UNIVERSITY ] 
 
OVERDUE. 
 
 wir 1934 
 
 LD 21-100m-7,'33 
 
YC 39910 
 

 i ^i