RULE: AMIDINE SALTS, ETC. 3

I L-Amidine Salts and the Constitution qf the so - ca Ilc d 1932 in oh y d ?,ins. By HAROLD GORDON RULE.

THE iminohydrins, or isoamides, are first meiitioiied by Eschweiler (Bw., 1897, 30, 1003), who prepared them from thel corresponding imino-ether hydrochlorides by thel action of moist silver oxide or by the interaction of the free imino-ethers and water. The resultr

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4 RULE: AMIDINE SALTS AND THE

ing compounds, from their analysis and apparent unimolecular condition in aqueous solution, were represented as having the con- stitution R*C(OH):NH, isomeric with the acid amides.

Thus the formation of glycolliminohydrin, the first of these compounds to be obtained from the corresponding ethyl ether hydrochloride, was explained according to the equation

OH*CH,*C(OEt):NH,HCl+ AgOH = OH*CH,*C(OH):NH + AgCl+ EtOH,

the iminohydrin, together with a large proportion of glycollamide, being supposed to result from the direct hydrolytic action of the water present. I n addition to the above, lactiminohydrin and a-hydroxyisobutyriminohydrin were prepared and very shortly described.

The chief characteristics of these compounds, as noted by Esch- weiler, are their high melting points, fusion being generally accom- panied by decomposition, the liberation of ammonia by alkalis, and their peculiar reaction towards certain metiallic salts, the glycollic compound, for example, slowly giving a deposit of calcium glycollate on the addition of a solution of calcium chloride. The latter action was supposed t o take the course

20H-CH2*C(OR):NH + CaC1, + 2H20 = (OH*CH,*CO,)Ca + 2NH,Cl.

Eschweiler further states that the irriiiiohydrins are basic i 11 character, and cldims t o have isolated definite hydrochlorides of the general type R*C(OH):NH,HCl, which are neutral in aqueous solution.

The failure of all attempts to effect' an interconversion between the iminohydrins and their apparent isomerides, the acid amides, led to an extended investigation by Hantzsch (Ber., 1901, 34, 3142), who showed that these compounds were. comparatively strong electrolytes, having in reality a molecular weight double that assigned to them by Eschweiler. I n opposition to the latter author, Hantzsch finds the iminohydrin hydrochloride to be strongly hydrolysed in aqueous solution, and also comments 011

the fact that all the known iminohydrins are derivatives of a-hydroxy-acids." I n spite of numerous attlempte, however, he was unable to prepare other types. I n explanation OF the dis- covery that the iminohydrins were electrolytes of the general formula (R*CO*NH,),, they were represented as having the con- stitutJon NH:CR*O*NH,:CR*OH, the complex being supposed to ionise in aqueous solution into the ions (NH:CR*O)' and

* In a patent application Eschweiler makes the bare claim to have prepared wet- and bone-iminohydrins, but no further details are given.

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CONSTITUTION O F THE SO-CALLED IMINOHYDRINS. 5

(NH,:CR-OH)’. The failure to establish any relationship to the acid amides, despite the similarity between the structure of these compounds and thatt suggested above for the iminohydrins, was met by Hantzsch with the statement that “amides and isoamides (iminohydrins) are not isomerides, but polymerides, and their relations are theref ore different from those of genuine tautomerides, which possem equal molecular weights.” The hydrochloride of glycolliminohydrin was nevertheless formulated as

OR*CH,*C(OH):NH,Cl, in which case we should have a true isomeride of glycollamide exist- ing in combination with hydrochloric acid.

More recently, the behaviour in solution of glycolliminohydrin, lactiminohydrin, and their salta has been examined by Professor James Walker (see Note to preceding paper), with results which led him to the conclusion that, these compounds are not true amphot’eric electrolytes, and that the formula assigned to them by Hantzsch is incorrect. For this reason, and since all previous at’tempts to prepare imiiiohydrins other than a-hydroxy-deriv- atives had failed, pointing to the possibility that tho hydroxyl group was an integral part of the molecule, the following investiga- tion was undertaken.

Several representatives of this class have been prepare’d and examined, and all were found to possess the high molecular weight and saline properties characteristic of glycolliminohydrin. The early preparation of the methoxyacetic and the phenylacetic deriv- atives showed that< the formation of an iminohydrin was in no way dependent on the presence of an cchydroxy-group in the molecule of the interacting imino-ether. Subsequently, an ex- amination of the comparatively stable mandelic compound * led to the discovery that the iminohydrins are complex amidine salts of the general formula R*C(NH,):N€I,R*CO,H. Th;s was con- firmed by the synthesis of mandeliminohyclrin (mandelamidine mandelate) from m andelamidine hydrochloride and sodium mandelate,

C6H5*CH(OH)*C(NH,):NH,HC1 + C,H,*CH(OH)*CO,Na = C6H5*CH( OH)-C( NH,) :NH ,C,H,*CH( OH) *CO,H + NaCl,

and of Eschweiler’s original glycolliminohydrin (glycollami dine glycollate) from the corresponding amidine hydrochloride and sodium glycollate,

OH*CH,*C(NH,):NR,HCl+ OH*CH,*CO,Na =

I n connexion with the latter synthesis, for which glycollamidine OH*CH,*C(NH,):NH,OH~CH,*CO,H + NaCl.

* Seeipreceding paper by J. E. Mackenzie.

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6 RULE: AMIDINE SALTS AND THE

hydrochloride had first, t o be prepared, some of Eschweiler's work on the iminohydrin (amidine) salts has been repeated and several inaccuracies have been corrected.

From the above point! of view, a, review of the properties of the " iminohydrins " presents no peculiarities. Evidence of saline character is furnished by high melting points, insolubilit-y in ether or hydrocarbons, and by high electrical conductivities in aqueous solution, the latter in the case of the glycollic compound being very little short of the value for a typical salt such as sodium acetate. The reaction with metallic salts is seen to be an example of ordinary double decomposition, that between glycolliminohydrin and calcium chloride following the course 20H*CH2*C(NH,):NH,0H*CH,*C0,H + CaC1, =

20H*CH,*C'(NH2):NH,HC1 + (OH*CH2~C"0,),Ca.

The soluble substance left' in solution is glycollamidine hydro- chloride, and not ammonium chloride, as assumed by Eschweiler, and later by Hantzsch. Characteristic of amidine salts is the disruption which accompanies fusion and the readiness with which ammonia is evolved on treatment with alkalis, whilst the decorn- position suffered by the iininohydrins in general on heating with aqueous solvents is due t o hydrolysis of the amidine into amide and ammonia,. This is well illust'rated in thel case of the phenyl- acetic compound, where attempted crystallisation from alcohol was fouiid to lead to the production of phenylacetamide and ammonium phenylacetate, CH,Ph*C(NHz):NH,@HzPh*CO,H + H,O =

The contradictory statements of Eschweiler and Wantzsch in connexion with the neutrality of the " iminohydrin salts " are also made clear, since these authors believed that, the iminohydrin, (R-C(OH):NH),, was capable of uniting with two molecules of hydrochloric acid to yield two molecules of the salt,

R-C(OH):NH,HCl. The hydrochloride, in reality an amidine salt, as isolated by Escli- weiler, proved to be neutral when dissolved in water, whilst hydro- lysis measure'ments carried out by Hantzsch with a solution con- taining one molecular proportion of iminohydrin t o two of hydro- chloric acid naturally led to the conclusion khat the salt was considerably hydrolysed. The organic acid which is liberated in the latter case remains practically non-ionised in the presence of the excess of hydrochloric acid, thus accounting for the apparent dissociation values of 50 per cent. obtained by Walker (see Note to preceding paper) for glycolliminohydrin and lactiminohydrin

CH,Ph-CO*NH, -+ CH2Ph*C0,NH,.

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CONSTITUTTON O F 'I'LIE SO CRTdLEl) 1 MIINOI1YI)RINS. 7

ltyclrochloridea, and by the author for the iiietlioxyacetic aiicl iiiandelic derivatives.

Mechnrzisnz of t h e Interact ion of Iinino-etlhers mid Tl'cctrr.

Pinner, in his monograph on the imino-ethers (" Die Imidoather und ihre Derivate "), states that these compounds decompose slowly on keeping, generally giving rise to the alcohol and nitrile from which they are derived. I n some cases the nitrile may poly- merise on being liberated, whilst in others the decompositiofi may take place in a different manner and lead to the formation of an acid amide. An example of the' latter type is furnished by a-hydroxyisobutyrimino-ethyl ether (Pinner, Zoc. cit ., p. 37), which on attempted distillation decomposes into the corresponding amide and alcohol, and i t is probable that the interaction between benz- irnino-ethyl ether and water to form cyaphenin (Mackenzie, P., 1913, 29, 175) is due to the initial formation and subsequent poly- merisation of benzonitrile.

I n those reactions where water is present, however, other changes may take place. Imino-ethers are at once strongly alkaline' and readily hydrolysable compounds, and the work of Pinner has shown that the imino- and alkyloxy-groupings are extremely sensitive t o attack, the actual group or groups affected depending on the reagent employed. I n particular, ammonia reacts with imino-ether hydrochlorides with great readiness to form amidine salts. Although in no single instance was any trace of free ammonia observed during the above interact'ions between imino- ether and water, i t was found by experiment thatl the addition of a 11 equivalent of ainmonium mandelate to an aqueous suspension of mandelimino-ethyl ether not only doubled the yield of amidine mandelate, but the deposition of the salt commenced almost immediately after the addition had been made. It seems prob- able, then, that in the interaction of imino-ethers and water, the first step is autohydrolysis of a portion of the subst'aiice in the alkaline medium to form the ammonium salt of the corresponding acid,

R*C(OEt):NH + 2H20 = R*C(ONH4):0 + EtOH. This salt, then, reacts with more free imino-ether to give the

amidine salt or iminohydrin, R*C(ONH,):O + R.C(OEt'):NH =z

R*C(NFI,):NH,R*CO,H + EtOH. l t i this connexiou, Pinner, in describing the formation of

amidine hydrochloride from imino-ether hydrochloride and a slight excess of alcoholic ammonia, remarks on the precipitation of

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S RULE: AMIDINE SALTS AND THE

ammonium chloride, which then slowly dissolves with the formation of the soluble amidine salt.*

The production of amide is probably caused by direct hydro- lysis of imino-ether and amidine in the alkaline solution, and the amount4 formed in any given experiment, does not appear to bear any constant relation to that of the amidine salt!.

E X P E R I M E N T A L .

The method of preparation adopted by Eschweiler, and later by Hantzsch, in which the imino-et,her hydrochloride is added in small portions at, a time to an equivalent amount of silver oxide suspended in water, led to such small and variable yields that its use was abandoned. Yields of 30-35 per cent. were obtained by allowing the free imino-ethers to remain with excess of water for some days a t the ordinary temperature. During this time, the originally strong a1 kaline reaction of the iniii?cwt8her gradually disappeared, and a mixture of irninohydrin anti acid was produced. Atl firsfi the imiaohydrin was isolated by repeated crystallisation from a suitable solvent. I n some later cases, the dried products of reaction were extracted with ether in a Soxhlet apparatus, the iiisoluble iiniiiohydrin being left behind in a comparatively pure state.

‘ Glycolliminohydrin ” (glycol1 amidiiie glycollate) was prepared in a 30 per cent. yield by dissolving glycollimino-ethyl ether in excess of water and allowing the solution to remain for ten or twelve days. On evaporation to dryness in a vacuum over sulphuric acid, and repeated recrystallisation of the residual solid from alcohol, the pure iminohydrin was obtained in well-defined plates melting and decomposing a t 166-1 6 8 O . Eschweiler (Zoc. c i t . ) gives 161-162O.

I n the hope of isolating some definite oxidation or reduction product, an electrolysis of the iminohydrin in aqueous solution was carried out in a divided cell. An analysis of the electrode gases, however, indicated complete disruption of the iminohydrin mole- cule. Similarly, all attempts by chemical means to isolate a basic or acidic component other than ammonia or glycollic acid, both of which were believed to be products of hydrolysis, led to no result.

Earlier attempts t o prepare acet- and benz-iminohydrins were also unsuccessful (compare Hantzsch, loc. cit., and Mackenzie, P., 1913, 29, 175), the only recognisable products of reaction in the

* Since the above WBP wribten, a paper has been published by A . Knorr (Ber., 1917, 50, 229), in which the aut’hor claims to have shown conc1usivc;ly Ohat free ammonia does not, react with free imino-ethers, but that amidine hydrochlorides are formed from ellern by reaction with ammonium chloride.

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CONSTITUTION OF THE SO-CALLED IMINOHYDRINS. 9

case of benzimino-ethyl ether being benzamide, cyaphenin, and a little ethyl benzoate. The first indicatdon that the presence of an a-hydroxy-group was not an essential condition for the formation of an iminohydrin was given by the preparation of methoxyaceb iminohydrin .

~ethoxyacetimino-eth.yl Ether, CH,-O*CH,*C(O-C,H,):NH.

Methoxyacetonitrile (29 grams), prepared from paraformaldehyde according to Wedekind’s method (Ber., 1903, 36, 1383), was dis- solved in ether and treated with an equivalent (24 c.c.) of absolute alcohol. The solution was cooled in ice, and dry hydrogen chloride (15 grams) passed in. After a short time, the liquid separated into two layers, and subsequently methoxyacetimino-ethyl ether hydrochloride crystallised out.

Some of the hydrochloride (16 grams) was shaken with ether and a concentrated solution of potassium carbonate. Much carboil dioxide was evolved, and the ethereal extract, after drying over sodium sulphate, was distilled. The boiling point of the distillate slowly rose to 136O, where i t remained constant. The yield of methoxyacetimino-ethyl ether (b. p. 136O) was 5-5 grams.

The imino-ether is a colourless liquid with a peculiar odour; it is alkaline to litmus and miscible in all proportions with water. Ammonia is readily evolved on treatment with alkalis.

0.1789 gave 0.3381 CO, and 0.1474 H,O.

It is probable that the substance was not. quite pure, since all imino-ethers decompose to some extent on heating. An attempt to purify a portion by distillation under 50 mm. pressure gave a distillate passing over a t 66-67O. This specimen on analysis proved to be no purer than the above.

Met hoxyacetiminohydrin ” ( m e t hoxyacet antidime met hox y- acetate) was obtained by allowing the free imino-ether (12 grams), mixed with excess of water, to remain at the ordinary tempera- ture for five weeks. The water was removed in a vacuum over sulphuric acid, and the resulting mixture recrystallised repeatedly from alcohol containing about a third of its volume of benzene. The iminohydrin (2.2 grams) was obtlained in large, well-shaped needles melting a t 162-164O :

C=51*52; H=9*22 . C5H,,O2N requires C = 51-25 ; H = 9-47 per cent.

0.1835 gave 0.2715 CO, and 0.1332 H,O.

It is readily soluble in alcohol and moderately so in water.

C=40*35; H=8.06. C6H1404N2 requires C = 40.42 ; H = 7.93 per cent.

In On heating with aqueous ether or benzene it dissolves sparingly.

sodium hydroxide, ammonia is evolved. B*

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10 RULE: AMIDINE SALTS AND THE

M o l e c i d i l r I V e i y h ~ i i i A pcc)?[ .s rS’ol(1ctiott (Cryoscopic N c t A od) .

Using 20 grams of solvent, the following data were obtained

0.1225 gave A t = - 0.129O. (K= 1870) :

M.W. = 89. 0.2481 ,, At= - 0.250’. M.W. -= 93. 0.3067 ,) A t = - 0.309’. M.W. = 93. C,,FI,,0,N2 requires M.W. = 178, hence at the above dilutiolls the

substance is almost completely ionised

Electr.ical Cotaductivity in IT’ater nt 25’.

The following determinations were made, using electrodes covered with a deposit ol “grey” platinum, and t o reduce still further errors arising from the oxidation at the electrodes, the electrolyte a t each dilution was freshly prepared from a stock solution bj7 the addition of the requisite amount of water (pZ5 = 1.6 x 10-6).

An N/20-solulion was prepared by dissolving 0.8907 gram of the ‘‘ iminohydrin ” up to 100 C.C.

...... 20 40 100 200 400 1000 2000 ,u~~....,. 60.9 64.0 67.S 69.8 50.8 71.8 72 0

At dilution v=2000 oxidation was noticeable, as shown by the dropping of the cell-resistance. The figures show methoxyacet- iminohydrin to be a good electrolyte, with a conductivity a t high dilutions comparable with that of glycollirninohydrin, for which Hantzsch finds ~ ~ ~ = 7 9 . 5 at ~ ~ 2 0 4 8 .

Hydrolysis of &€ e t hotyxyn ce t i )ti ino hydrin Hydrocli loride.”

According to Eschweiler and Hantzsch, the iminohydrins form hydrochlorides of the general type R*C(OH):NH,HCl, salts which are considerably hydrolysed in aqueous solution. Walker (see Note) to preceding paper) finds this hydrolysis in the case of the glycollic and lactic derivatives t o approximate t o 50 per cent. in A’ / 8 -so 1 u t i on.

The hydrolysis a t the same dilutdon of methoxyacetimiriohydrin hydrochloride was measured by the methyl acetate catalysis method, and found in this case also to be almost exactly 50 pcr cent,

Experiments directed towards the preparation of the unsubsti- tuted “ iminohydriiis ” corresponding with benzoic, phenylacetic, and acetic acids met a t first with no success. As has been already stated, beiizimino-ethyl ether reacts with water to give cyaphenin, and failure in the cases of phenylacet- and acet-imino-ethyl ethers was subsequently found t20 be due to hydrolysis of the “imino-

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CONSTITUTION O F TIIE SO-CALLED IMINOHYDRINS. 1 1

hyclrins ” during attempted purification by crystallisation. The two latter compounds were eveukually obtained from the crude reaction mixture after removing the accompanying acid amid0 by extraction with ether in a Soxhlet apparatus.

“ L4 cetinainohydrin ” ( A cetnnaidine A ce t t r t c ) , CH,*C(NH,) :NH,CH,*CO,H.

Acetimino-ethyl ether hydrochloride, prepared from acetonitrile (37.5 grams), alcohol, and hydrogen chloride in the usual manner, was converted into the free imino-ether by shaking with ether and a concentrated solution of potassium carbonate. The bulk of the ether was cautiously removed on the water-bath, and thel residual liquid mixed with excess of water in a stoppered bottle. After ten weeks, the still faintly alkaline solution was evaporated to dryness in a vacuum over sulphuric acid, and the solid residue extracted with ether in a Soxhlet apparatus. The residue, melt- ing a t 66-148*, was partly soluble in benzene, the solution deposit- ing crystals of acetamide (m. p. 79-82O). The insoluble portion, amounting to 3 grams, melted a t 155-175O. The latter was purified by solution in cold alcohol and precipitation with benzene, giving a final product melting and decomposing atl 185-187’.

All attempts to recrystallise i t from warm alcohol or ethyl acetate, with or without the addition of benzene, resulted in the de corn p osition of the iminoh y dr in.

Qualitative tests showed that this substance was a good electro- lyte, whilst its high melting point, insolubility in ether, and the evolution of ammonia with sodium hydroxide, showed it to be of the same class of substances as glycolliminohydrin. Owing to the low yield and its unstable nature, i t was not further examined.

( ( Ph enyla cet imitr oh ydrin ” (Phen ylnce t a midi?, e Phen ylacet rr t e), C‘,H,*CH,*C(NH,) :NII,CY6H5*CI12.C0,H.

Free phenylacetimino-ethyl ether, prepared from phenylaoeto- nitrile’ (Pinner, ‘‘ Die1 Imidoather,” p. 66), was allowed to remain in contact with water a t the ordinary temperature for several weeks. The semi-solid mass was filtered, and the solid portion, after drying, extracted with ether in a Soxhlet apparatus. After thirty hours’ extraction, the iminohydrin was left b e h i d in a pure state, melting and decomposing a t 227-230° :

0.1586 gave 0.4138 (20, and 0.0974 H,O. C,,H,,O,N, requires C = 71.10 ; I3 = 6-72 per cent.

By solution in ethyl acetate and precipitation with benzene, a product of the original melting point was obtained in very fin0

C=71 13; H=6*82,

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12 RULE: AMIDINE SALTS AND THE

needles. The substance is very sparingly soluble in water, soluble in alcohol, and insoluble in benzene or ether. With aqueous alkalis, ammonia is readily evolved, and the compound is of the same unstable nature as acetiminohydrin, attempted recrystallisa- tion from alcohol or water leading to partial decomposition into amide and the ammonium salt of the corresponding acid. For this reason, it was not further examined.

The four ‘( iminohydrins ” described above, derivatives of glycollic, methoxyacetic, acetic, and phenylacetic acids, were not suited t o a detailed investigation on account of their instability towards solvents and their general physical properties. A more convenient subject for examination was found in ‘‘ mandeliminohydrin.”

( ( ~ a ? 2 d e l i ? ~ i i . l ~ o l ~ ~ ~ ~ ~ ~ } ~ ’’ (Jfa?idelarnidiiz e iiandellrt e) , C,H,*CH (OH)* C(NH,) :NH,C,H,-CB(OH)* C0,H.

This compound had already been obtained in small quantities by Mackenzie (see precediiig paper) by the interaction of aqueous silver oxide and mandelimino-ethyl ether hydrochloride. I n the preparation of larger quantities, it was obtained from benzaldehyde as follows.

Moist potassium cyanide (80 grams) was placed in a flask and covered with an ethereal solution of one equivalent (106 grams) of benzaldehyde. The whole was cooled in ice, and rather less than one equivalent (50 c.c.) of concentrated hydrochloric acid added slowly with constant shaking. The ethereal solution was decanted and dried for twenty-four hours over anhydrous sodium sulphate, after which it, was poured off and cooled in ice. Equivalent amounts of alcohol (46 grams) and dry hydrogen chloride (36.5 gramsj were added, and after a shortl time the liquid became almost solid, owing to the separation of mandelimino-ethyl ether hydrochloride. I n a few hours the latter (135 grams) was collected.

The hydrochloride was suspended in ether and shaken with a conoentrated solution of potassium carbonate. On removal of the ethereal layer and evaporation of the solvent in a vacuum, the free imino-ether (87 grams) remained as a white solid.

The imino-ether was introduced into a stoppered bottde contain- ing excess of water, and the latter placed in a shaking machine. After five or six days, the bulk of the solid suddenly passed into solution, when the reaction mixture was removed and the water evaporated in a vacuum over sulphuric acid. The dry residue was transferred to a Soxhlet apparatus and extracted for some hours with ether, leaving an insoluble portion melting and decom- posing at about 180° which, after one crystallisation from alcohol,

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CONSTITUTION OF THE SO-CALLED IMINOHYDRINS. 13

gave the pure iminohydrin (25 grams), melting and decomposing a t 185-187O. Mackenzie quotes 173-179O (see preceding paper), the actual figure depending very much on the rate of heating.

Mandelamidine mandelat e crystallises in colourless plates, in- soluble in ether, benzene, or light petroleum, sparingly soluble in water (100 grams dissolve 1.87 grains atl 25O), rather more readily so in ethyl alcohol, and moderately so in methyl alcohol (100 grams dissolve 4.80 grams a t 25O). It’ is comparatively unaffected by solvents, and can be recovered from them unchanged, whereas glycolliminohydrin recovered, for example, from a solution in hot alcohol, has always a decidedly lower melting point than the start- ing material.

ilfolec.ztlw 1 Veigh t itL A q t6 eo us Solu t i o i ~ (G’r~oscoyic Met k od) .

Using 20 grams of solvent, the following data were obtained

0*1210 gave A t = -0.073. M.W.=155.

C,,H,,O,N, requires M.W. = 302, hence a t these dilutions the compound is almostl completely ionised.

I n boiling methyl alcohol (pure anhydrous), the following figures were obtained, using an electrically heated modification of Beck- mann’s apparatus, jacketed in a vacuum tube.

(K = 1870) :

0.2348 ,, A t = -0.147. M.W.=149.

Weight of alcohol taken, 27.91 grams (K=860). 0.5340 gave E = 0.080. M. W. = 206. 0.9923 ,, ,, =0.150. M.W.=204. 1.384 ,, ,, ~ 0 . 2 1 4 . M.W.=200. As was to be expected, these figures indicate partial ionisation

only of the compound in methyl alcohol.

Electrical Conducthit?/ in ?Vater a t 2 5 O .

As in the case of methoxyacetirninohydrin, the electrodes used were coated with “grey .’ platinum, but at8 the higher dilutions,

1 1 -- 400 and above, oxidation was made apparent’ by the falling resistance of tlhe cell. The solution a t each dilution was freshly made u p from an N/20-stoclr solutdon containing 1.511 grams in 100 C.C. The water used had a specific conductivity value of 1.4 x 10-6 a t 25O.

v ...... 20 40 100 200 400 1000 2000 p,,...... 43.0 46.0 51.0 53.0 54.4 55.2 56.2

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14 RULE: AMI1)INE SALTS AND THE

(‘ M a ?rdelinziiaohydi.irt E l ydrochloride. ”

The hydrolysis in aqueous solution of the (‘hydrochloride of glycollimiiiohydrin ” was measured by Hantzsch by determining the electrical conductivity of a solution containing one molecular proportion of the bimolecular “ iminohydrin ” and two molecular proportions of hydrogen chloride. The figures obtsined indicated extensive hydrolysis. As already stated, Walker, using the methyl acetate catalysis method, found almost exactly 50 per cent. of the hydrogen chloride in the uncombined state in N/8-solution. The hydrolysis of the mandelic compound, determined by the latter method, was again found to be 50 per cent. in N/1&solution. On the other hand, Eschweiler states (compare Hantzsch, Ber., 1901, 34, 3154) that glycolliminohydrin hydfochloride, obtained by evaporation of the solution of iininohydrin in hydrochIoric acid, is a neutral salt having the structure OH-CH,*@(OH):NH,HCl.

(‘ Mandeliminohydrin,” on being treated with excesq of aqueous hydrochloric acid and evaporation in a vacuum over solid potassium hydroxide, was found t o retain exactly a half-equivalent of acid, which could be estimated by titration with standard alkali in the presence of methyl-red. This solid hydrochloride showed no definite melting point, but ‘I mandeliminohydrin,” when dissolved in hot dilute hydrochloric acid, deposited, on cooling, well-f orined crystals of a hydrochloride nielting at 215-219O. These crystals proved to be1 neutral in aqueous solution, and evolved much ammonia with sodium hydroxide.

*4 ction, of Alkalis on ( ( ~mndeliiziitioltydi.irL.“

I n the course of some experiments on the action of alkalis on mandeliminohydrin,” an aqueous solution of the latter was

treated with exactly one molecular equivalent of sodium hydr- oxide. No ammonia could be detected after remaining for some minutes in the cold, but on warming the strongly alkaline solution, a considerable evolution of the gas was observed. The mixture was boiled until the evolution of ammonia ceased, when the resi- dual liquid was found to be neutral. On cooling, a crop of crystals was deposited melting at 128--132*. These, after crystal- lisation from alcohol, melted a t 131-13Z0, and proved to be pure mandelamide. The aqueous mother liquor contained sodium inandelate and yielded free mandeIic acid on acidification. No other product could be detected.

These results suggested that, the basic portion of the irnino- hydrin was set free by alkali and subsequently decomposed with

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CONSTITUTION OF THE SO-CALLED 1MINOHIYI)RINS. 15

evolution of amrnonia. Attempts to isolate a base soluble in ether were only successful when the aqueous alkali originally in use was replaced by a saturated solution.

When the finely powdered iminohydrin was rapidly shaken in a separating funnel with ether and saturated aqueous potassium hydroxide, the ethereal layer left, on evaporation in a vacuum, a very small amount of a white solid. This substance melted at 98--110°, was soluble in water, giving a, powerfully alkaline solu- tion, and after a short time decomposed, with the evolution of much ammonia. These properties are those of an amidine, mandel- amidine, C,H,*CH(OH)*C(NH,):NH (Beyer, J . pr. Chem., 1885, [ii], 31, 383), melting a t llOo. The neutral hydrochloride melt- ing a t 215-219O obt’ained above should then correspond with mandelamidine hydrochloride, C,H,*CH( OH)*C( NH,) :NH,HC1, which melts a t 213-214O (Beyer). A specimen of the latter pre- lmreci from mande81imiiio-ethy1 ether hydrochloride a i d alcoholic ammonia was found t o melt at 219-220O.

The behaviour of “ mandeliminohydrin ” towards acids and alkalis, coupled with the characteristic reaction of glycollimino- hydrin with calcium chloride, resulting in the deposition of calcium glycollate, pointed t o these compounds being, in reality, amidine salts of the general type R*C(NH,):NH,R*CO,H.

Synthesis of (‘ Mandel.lnzi?2ohycin.~’

This constitution was readily confirmed by the formation of the iminohydrin ” on mixing in warm aqueous solution equivalent

amounts of mandelaniidine hydrochloride and sodium mandelate. On cooling, the solution deposited hard nodules melting and decomposing a t 1 75-180°, which, after recrystallisation from alcohol, showed the characteristic plate formation of “ mandel- iminohydrin,” and melted and decomposed a t 184-186O.

Synthesis of “ Glycollimi~zohydrit~ .,’ Equivalent amounts of sodium glycollato and glycollamidine

hydrochloride (for preparation, see later) were mixed in aqueous solution. After evaporating t o dryness, ext’raction with alcohol removed “ glycolliminohydrin,” melting at 166-168O.

“ p-Ch1oromandeliminohiyd.ri.n ” ( pChloronzandelamidirte p-Chloro- nr a d e l a t e ) , C,H,Cl-@H (OH)*C( NH,) :NH , C,H,Cl-CH( OH)=CO,H.

This compound was prepared for the purpose of comparing its physical constants with those of the mandelic derivative before the

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I6 RULE: AMIDINE SALTS AND THE

constitution of the iminohydrins as amidine salts had been estab - lished. The preparation was a somewhat lengthy process, start- ing with the conversion of pchlorotoluene into Pchlorobenzyl- idem chloride, C,H4C1*CHC1,, by the action of chlorine on the boiling liquid under the influence of rays from a (( Uviol " mercury- vapour lamp. The chloro-compound was heated in a sealed tube a t 170° with water, yielding p-chlorobenzaldehyde, and the latter extracted with ether. The ethereal solution, after drying over sodium sulphate, was used direct for the preparation of p-chloro- mandelimino-et hyE ether, C,H4C1=CH (OH) C( OEt) XH, by the method used above for the mandelic compound. Owing to the great tendency of the chloroaldehyde to oxidise in air, it was found necessary t o carry out the reaction in closed vewds in an atmo- sphere of carbon dioxide. idene chloride gave 8 grams of the free imino-ether.

'The compound crystallised from ether in well-defined plates melt- ing a t 107-logo. When recrystallised from light petroleum, i t melted a t 108-110°.

The crude product tends to oxidise in air, becoming red, but the pure substance can be kept for some weeks without much dis- coloration. It is sparingly soluble in water, soluble in dilute hydrochloric acid o r alcohol, and readily so in hot benzene, from which it is precipitated by light petroleum.

An attempt to determine the chlorine content by Stepanov's method, using alcohol and metallic sodium, led t o too high a figure being found, and i t was noticed that decomposition of the imino- ether had taken place in such a way as to lead t o the production of hydrogen cyanide.

Using the Carius-Volhard method, the following figures were obtained: 0.1172 gram was heated in a sealed tube with 0.2242 gram of silver nitrate and 2 C.C. of fuming nitric acid. After the reaction, the oxides of nitrogen were removed and the unchanged silver nitrate was titrated with thiocyanats, of which 7.35 C.C. (0*1052N) were required :

Twenty-f our grams of p-chlorobenzyl

Cl= 16.5. C,,H,,O,NCl requires (21 = 16.6 per cent.

'' Chloromandeliminohydrin " was prepared, in small quantity only, by the method adopted in the case of the mandelic derivative. Continuous extraction of the dry product with ether separated the mixt'ure into two portions.

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CONSTITUTION OF TRE SO-CALLED IMINOHYDRINS. 17

p-Ghloroman d elamide, C,H,Cl*CH (OH) *CO*NH,.

The ethereal extract deposited a white, crystalline substance which, on crystallisation from benzene, melted a t 122-123O. Analysis showed this to be the expected pchloromandelamide. On hydrolysis with alkali, it yielded ammonia and a salt of chloro- mandelic acid.

0.1162 Gram heated with 0.2626 gram of silvsr nitrate and fuming nitric acid required for titration 9.10 C.C. of N/lO-thio- cyanate. C1= 19.4.

C8H,0,NC1 requires C1= 19.1 per cent!. The amide is soluble in alcohol, sparingly so in ether, and very

sparingly so in benzene. p-Chloromandelamidine p-chloro- mnndelate was left behind in the crude state after extraction with ether as a white powder melting a t 170-180°. Recrystallisation from a mixture of alcohol and benzene raised the melting point to 186-195O (with decomposition).

This compound proved to be unexpectedly unstable, and very readily decomposed with the evolution of ammonia on heating with solvents. Owing t o its instability and the fact that its percentage composition does n o t differ from that of the amide with which it i,s liable to be contaminated, it was not further examined.

Treatment with dilute hydrochloric acid and subsequent recrystal- lisation from alcohol yielded the crystalline p-chloromandelamidine hydrochloride , C,H,Cl-CH (OH)-C { NH,) NH , H C1, melting and decomposing a t 252-253O :

0.3360 required 15-20 C.C. Nl10-AgNO,. C1’ = 16-04 C,H,ON,Cl,HCl requires C1’ = 15*97 per cent.

Amidiize Salts.

Some compounds of this type have been described by Eschweiler under the heading of “iminohydrin salts,” but since much of t,he data furnished by this author is inaccurate, and since, moreover, he was under a misapprehension as to the structure of the com- pounds with which he was dealing, it was thought desirable to repeat certain of the preparations.

Glycollamidine Hydrochloride, OH*CH,=C(NH,):NH,HCl.

Eschweiler (ibid.) describes glycolliminohydrin hydrochloride as being prepared by the evaporation of a solutlion of the iminohydrin in an equivalent’ amount of dilute hydrochloric acid. The re-

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18 RULE: AMIlXNE SALTS AND THE

crystallised product is quoted as melting a t 135O and bavirlg the structure OH* CH,-C (OH) :NH ,HC1.

Glycollamidine glycollate, prepared froin the free imino-ether by treatment with water, gave, on evaporation with hydrochloric acid, a crude product melting a t 130--150". After repeated purification by solution in hot alcohol and precipitation with benzene, the hydrochloride was obtained in very fine needles melt- ing att 150-151°.

I n larger quantities, t,his salt was prepared from glycolliniiao- ehhyl ether hydrochloride and alcoholic ammonia according to the general method recommended by Pinner ( l o c . cit.). After puri- fication from 98 per cent, alcohol. a product of the above melting point was obtained.

0.2003 was distilled with excess of sodium hydroxide and the ammonia trapped in 25 C.C. of (1.2036 iT-sulphuric acid. The excess of acid required 7-70 c.c. of 0.1934 #-sodium hydroxide. N = 25.17.

0.1037 treated with 20 C.C. of NIlO-silver nitrate required for titration 10.65 C.C. of N/lO-ammonium thiocyanate. C1= 31.97.

C,H,ON,,HCl requires N = 25.34 ; C1= 32.08 per cent. The salt is sparingly soluble in alcohol and practically insoluble

It is very readily soluble in water and in benzene or ether. deliquescent in air.

Glycollamidine Sulph>ate, (OH.CB,*C(NH,):NH),,H,SO,.

Glycollamidine hydrochloride was treated with an equivalent of sulphuric acid, and the excess of water evaporated on the steam- bath. Recrystallisation from aqueous alcohol gave the sulphate in colourless leaflets melting and decomposing a t 205O. Eschweiler (Zoc. c i t . ) gives 150° as the melting pointl of glycolliminohydrin sulphat'e, prepared in a similar manner :

S = 12.78. 0.2042 gave 0.1900 BaSO,.

The salt is nob deliquescent, is readily soluble in water, and very (C,H,ON,),H,SO, requires S = 13.02 per cent.

sparingly so in absolute alcohol.

(n'lycoltamicfiine Hyd?*oge?t, Sulp?~/rfc7, OH.CH,*C(NH2):NH,H,S0,.

I n order to ascertain if Eschweiler's sulphate, melting a t 150°, were the hydrogen sulphate, glycollamidine hydrochloride was treated in aqueous solution wit'h exactly two equivalents of sulphuric acid and evaporated to dryness in a vacuum over sodium hydr- oxide and sulphuric acid. The product was quite free from

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chloride, and, after drying on porous porcelain in a vacuum, melted at 65-67O after having softened at, 63O. On recrystallisation from aqueous alcohol, leaflets melting at’ 150-1‘75° were deposit’ed, which proved on analysis to contain more than 90 per cent. of the normal sulphate. Even from solvents containing a large excess of acid, the crystals deposited were mainly of the normal salt.

G 7y c oUc/ nz idin e Nitro t e , OH- C H,* C (N H3) : N H , H NO,.

This substance was obtained by evaporating on the steam-bath equivalent amounts of glycollamidine hydrochloride and aqueous ilitric acid. Recryst’allisation from aqueous alcohol gave the pure nitrate, melting a t 110-11lo (Eschweiler gives 9 5 O as the melting point of glycolliminohydrin nitrate).

A product melting a t l l O - l l l o was also obtained from glycoll- aniidine glycollate (iminohydrin) and nitric acid :

0.2330 gave 0.1504 GO, and 0.1074 H,O. 0.1497 ), 39-10 C.C. N, (dry) a t 10-5O and 747 mm. N=30.88.

C=17*58; H=5.15.

C,H,ON,,HNO, requires C= 17.52 ; H= 5-15 ; N =30*68 per cent.

The salt is very readily soluble in water, and practically in- soluble in absolute alcohol, benzene, or ether. From aqueous alcohol, it is deposited in leaflets which are stable in air.

Eschweiler’s ‘‘ lactiminohydrin sulphate ” (lactamidine sulphate) is correctly quoted as melting at about 1 9 8 O . A specimen pre- pared from the “iminohydrin” was found to melt and decompose at 2OO-20Zo. The hydrochloride and nitrate have already been described by Pinner.

Sum rri a r y . (1) The iminohydrins or isoamides, formulated by Eschweiler as

R*C(OH):NH, and by Hantzsch as NH:CR*O*NH,:CR*OH, have been,shown to be amidine salts of the general type

R*C(NH,):NH,R-CO,H. This structure has been confirmed by the synthesis of the maiidelic compound and of Eschweiler’s original “ glycolliminohydrin.”

(2) It is suggested that the production of amidine salt by tlie reaction between imino-ether and water takes place mainly through the intermediate format.ion of the ammonium salt of the corre- sponding acid, which by subsequent reaction with free imino-ether gives rise to the amidine salt.

(3) Certain inaccuracies of Eschweiler in reference to “imino- hydrin ’’ (amidine) salts have been corrected.

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20 WERNER : THE PREPARATION OF a-NAPHTHOLPHTHALEIN.

I n conclusion, I desire t o express my thanks to Professor Walker, a t whose suggestion the above work was undertaken, for the interest he has shown throughout its course. 1: am also indebted to the Earl of Moray Research E’und for a grant which has covered most of the expenses in connexion with this research,

CHEMISTRY DEPARTMENT, UNIVERSITY OF EDINBTJICGH. [Received, J u l y 2nd, 1917.1

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