235 FOSTEB ON ACETOXYBENZAMIC ACID. XX.-On Acetoxybenzarnic Acid an Isomer of Wippuric Acid. BY G. C. FOSTER. IF we regard hippuric acid as benzoyl-glycocol or glycocol in which an atom of hydrogen is replaced by benzoyl it seems natural to expect that an acid isomeric with and analogous to hiypuric acid might be obtained by replacing an atom of hydrogen in oxgbenzamic acid (syn. benzamic acid amidobeneoic acid) by ncetyl. From the results recorded in this paper it appears that such is the case. When oxybenzamic acid is heated in a sealed tube with about half its weight (rather more than one equivalent) of monohydrated acetic acid the whole mass becomes quite fluid at about 130' or 140°C. but solidifies almost entirely at about 160° all that remailis liquid king the portion of acetic acid used in excess.The reac-tion which takes place is the following :-C7H7N0 + C2H,02 = C,N,NO +-H20.* Oxybenzamic Acetic Acetoxybenzamic acid acid. acid. Using at a tirm from 15 to 20 granimes of oxybenzamic acid T found that thc reaction 'CI tij quitc complete after an hour's heating to 160° especially if advautage had been taken of the period of complete liquefaction to mix thc materials thoroughly. The same product is also formed by tile reactioii of chloride of acetyl on ovybenzamate of zinc-f at 100" C7€I,%nN02 + C2H,0Cl = C,H,NO + ZnCl. Oxybenzamate of Chloride of Acetoxybenzamic zinc. acetyl. acid. On mixing chloride of acetyl with oxybenzamate of zinc sufficient heat is given off to volatilize a considerable part of the chloride of acetyl if care be not tziken to condense it and tlie whole quickly soliclifies to a hard mass (probably a combination of the two sub-stances analogous to the combination of hydrochloric acid with oxybenzamic acid) which in a sealed tube at looo melts arid then again gradually solidifies ; complete solidification iiidicates the end of the reaction.Oxybenzamate of zinc heated with two equivalents of acetic acid or a mixture of equivalent quantities of hydrochlorate of oxybenzamic acid and acetate of calcium with a little acetic acid yields the same product ; but neither of these processes is advanta- geous on account of the high temperature required and the difficulty of thoroughly mixing the materials.* C = 12 0= 16 + Oxybenzamate of zinc is easily obtained by mixing solutions of chloride of zinc and oxybenzamate of calcium. It separates as a granular precipitate which is very easily washed on a filter. It is nearly insoluble in water but soluble in acetic acid. *3624 grm. dried at loo" was boiled with carbonate of sodium till completely decomposed the resulting carbonate of zinc yielded on ignition .0921 grm. oxide of zinc. Calculated. Found. Zinc percent. . . . . 21.16 20.42 I have found the formation of this salt to be a convenient method of separating oxybenzarnic acid from impure solutions. The substance yielded by these reactions is easily purified. It is sufficient to dissolve it in an alkali to precipitate the solution by hydrochloric acid and to crystallize the precipitate two or three times from boiling water or alcohol.Any colouring matter which still adheres to the product thus obtained may be completely removed by animal charcoal. I have named the new substance ace~oxybenxamicacid. Dried over snlphuric acid it does not lose weight at 100". -3788 grm. prepared fcom acetic and oxybcnzamic acids gave ,8382grm. carbonic acid and -1'766grm. water. -2913 grm. prepred ffom chloride of acetyl and osybenzamate of zinc gaw -6396 grm. carbonic acid and *139 grm. water. *4363grm. of another similar preparation gave 9677 grm. car- bonic acid and ,1987' grm. water. *3302grm. of the same product heated with soda-lime gave a platinum-salt containing 02375grm.platinum.* .4-1.42 grm. of the same product gave 29.2 ec. nitrogen at 0" and '760 mm. pressure. Calculated. Found. f 1.. L4. Mean. C 108 6033 60.36 59.88 60.49 - - 60.24 H 9 5.03 5.18 5.23 5-06 - - 5-16 N 14 7.82 - - - 7.50 8.25 8.02 0 48 26.82 - - - .- .__ 26.64 __I_ C,H,NO 179 100*00 100*00 Acetoxybenzamic acid is obtained as a white powder which under the microscope is seen to be formed of needle-shaped crystals. It is almost insoluble iu cold water and in ether and is onlyrnoderately soluble in boiling water or in cold alcohol j in boiling alcohol it dissolves easily. It has a slightly bitter taste a good deal resembling that of nitre. Like its isomer liippuric acid it dissolves readily in a solution of common phosphate of sodium giving an acid reaction to the liquid but is reprecipitated by acetic or a mineral acid.It is soluble in strong sulphuric acid without colouration in the cold and also in glacial acetic acid ; these solutions are precipitated by dilrrtion with water. A mixture of * In the decomposition of acetoxybenzamic acid by soda-lime very little ammonia is formed ; nearly the whole of the nitrogen is given off as aniline. FOSTER ON ACETOSYBENZAMIC ACID. acetoxybenzamic acid with sufficient strong hydrochloric or nitric acid to make it flow eqsily becomes nearly solid on standing for a few minutes but it was found that a mixture of hydrochloric acid and acetoxybenzamic acid loses all its hydrochloric acid when dried under a bell-jar over lime and snlphuric acid.At about 200"acetoxybenzamic acid sublimes somewhat rapidly ; it melts between 220" and230" and enters into ebullition at about 260" apparentiy undergoing decomposition at the same time. It may be boiled for a long time with water and even with dilute acids without undergoing perceptible change ; but when heated in a sealed tube with hydrochloric or dilute sulphuric acid to about 140"it is decomposed into oxybenzamic and acetic acids just as hippuric acid is decomposed under similar circumstances into glycocol and benzoic acid. A quantity of hydrochlorate of oxy- benzamic acid thus obtained gave the following results on analysis : r- ~3767grm. burned with chromate of lead gave -677 grm. car- bonic acid and ,1719 grm.water. *4399em. gave *3624grm. chloride of silver. Calculated. Found. Carbon . * . . 48.42 49.01 Hydrogen . . . 461 5.07 Chlorine . . . . 20.46 20.39 Another quantity of acetoxybenzamic acid was deromposed by dilute sulphuric acid of 10 per cent. When the decomposition was complete the contents of the tube were transferred to a retort and distilled. The distillate was saturated with carbonate of barium filtered and evaporated. The barium-salt so obtained proved to be acetate of barium. $8039grm. dried at 120° gave -7365 grm. sulphate of barium. Calculated. Found. C2W,Ba0 Barium per cent. . . . 53.73 53.72 The residue iu the retort deposited on cooling crystals of sulphate of oxybenzamic acid. Acetoxybenzamic acid is similarly decomposed by a.n alcoholic solution of hydrochloric acid but oxybenzamate and acetate of ethyl are formed at the same time as the corresponding acids.The FOSTER 03 ACETOXYBENZAMIC ACID. 239 decomposition takes place slowly in the cold but quickly at 100". On distilling the product of the reaction in a water-bath a light ethereal liquid possessing the smell and general properties of acetate of ethj-1 passed over with the excess of alcohol and was separated from it by the addition of water. The residue in the retort crystallized on cooling in radiating needles. The crystals which mere very soluble in water and alcohol but slightly soluble in ether were recrystallized from water washed with ether and dried over sulphuric acid. *4748grm.gave -3501 grm. chloride of silver. -392 grm. gave -2924grm. chloride of silver. -5091 grm. burned with chromate of lead gave 09642grm carbonic acid and -2638grm. water. These results correspond to a mixture of the hydrochlorates of sxybenzamic acid and oxybenzamate of ethyl. Hydroehlorate of Found. Hydrochlorate of oxybenzamic acid. oxybenzamate of ethyl. Carbon . . . 48.42 5 1-65 53.60 Hydrogen . . 4.61 5.76 5.96 -Chlorine . . . 20.64 18.24 18.45 17.62 What was left of the crystals after making the above analyses was dissolved in water a slight excess of milk of lime added and the whole shaken up with ether. The ether left on evaporation an oily liquid apparently oxybenznmate of ethyl which was nearly insoluble iu water but soluble in hydrochloric acid giving a chloride insoluble in ether and combining readily with bichloride of platinum.The quantity of the platinum salt obtained was not sufficient for a determination of the percentage of platinum. The aqueous liquid from which the ether had been poured off was filtered and the excess of lime separated by carbonic acid. After being somewhat concentrated by evaporation it gave with chloride of zinc a precipitate resembling oxybenzamate of zinc. Attempts were made to obtain acetoxybenzoic acid C9H8OQ isomeric with benzoglycollic acid by the action of nitric oxide on a mixture of nitric acid and acetoxybenzamic acid and also by the action of nitrous acid on a briiling aqueous solution of acetoxyben-zamic acid but in both cases the only product was a nitro-substi- tution compound.Acetoqbewamate of pntassium was prepared by digesting a solution of tlie acid in strong alcohol with dry carbonate of potas- sium. It is exceedingly soluble in water and dissolves easily in alcohol but is precipitated from this solution by ether. From a solution in alcohol containing more tliaii about 10 per cent. of water,it is precipitated by ether in the form of a strong aqueous solution which solidifies only after standing for a considerable time. Acetoxybenzamate of sodium CgH8NaN0 + xH,O. -This salt was prepared in the same way as tlie potassium salt. It is very soluble in water and easily soluble in alcohol but can be obtained crystallized soinewhat inore easily than the potassium salt.It is insoluble in ether and is not deliquescent. -468 grm. dried between 120' and 1304 gave 01636 grm. sulphate of sodium. Calculated. Found. (:91-l,Eax0, ~ Sodium per cent. . . 11.44 11 -32 Acetoxybenzamate of barium C,H,BaKO + 1 $€I,O. -0btaiiied by saturating a hot aqueous solution of the acid with carbonate of barium. It is very soluble in water and crystallizes by the spontaneous evqoration of its solution in minute radiating needles grouped together in tufts. It dissolves readily iii spirit of wine but is precipitated from a strong aqueous solution by absolute alcohol. It loses only a part of its matcr of crystallization at 100"; for analysis it was dried between 138' and 145'. 1.8858 grm. dried over sulphuric acid lost -1812 grm.water between 130"and 14So. *8776grm. lost *Of387grm. water at the same temperature. ~6464grin. of the dry salt gave *3027grm. sulphate of barium. -3783 grrn. gave -1774 gri. sulphate of barium. 03918 grm. gave .1824 grrn. sulphate of bariuln. a9185 grm. burned with chromate of lead gave 1.4625 grm. carbonic acid and ,288 grin. watcr. Calculated. Found. 108 43.81 /--43.43\ c9 HE3 8 3-25 --3.48 Ba 68.5 27.79 27.54 27.32 27.42 --.__ N 14 5.68 -48 19.47 --03 -__. _I__-C9H,BaN0 246.5 100 00 FOSTER ON ACETOXYBENZAMIC ACID. 241 Calculated. Foyd. CSH,BaWO + 1iH,O -7 Water of crystallization . . 9.87 9.61 10.11 Acetoxybenznmate of calcium C9R8CaN0 + l+H,O.-This salt was prepared by saturating the acid with milk of lime and removing the excess of lime by carbonic acid.It is only moderately soluble in cold water and can be easily obtained in well-defined crystals consisting of very thin rhombic plates by cooling its hot aqueous solution. ,6428grm. air-dry lost *081grm water at 130". -63 grm. lost *0781grm. water at 130". -2978grm. dried at 130° gave -1039 grm. sulphate of calcium. -2087grm. gave -0722grm. sulphate of calcium. ,342grrn. burned with chromate of lead gave *6786grm. car-bonic acid and *1337grm. water. Calculated. Found. -. h 108 54.55 /--54.12 C9 H* 8 4-04 -4.34 Ca 20 10*10 10.26 10.17 -N 14 7.07 --03 48 24.24 ---"-C9HsCaN0 + l+H,O Water of crystallization . . . 12.0 12.6 12.4 Acetate of lead gives with a solution of ail acetoxybenzamate a sticky precipitate which melts in boiling water and gradually dissolves; it is also soluble in alcohol.Nitrate of .doer and chloride of zinc give no precipitate with a nioderately strong solution of an acetoxybenzamate. With a con-centrzted solution nitrate of silver gives ft. prscipitste which blackens on boiling. Acetoxybenzamate of ethyZ.-This substance cannot be obtained by the process indicated by Stenhouse for the preparation of fiippurate of ethyl namely by heating the acid with alcohol saturated with hydrochloric acid. The manner in which acetoxy- benzamic acid is decomposed under these circumstances has already been described. When acetoxybenzamic acid and absolute VOL. XITI. R 242 FOSTER ON ACETOXYBENZAMIC ACID alcohol are heated together no apparent action takes place at looo; but at about 150" a compound is formed ahich is soluble in ether and can thus be separated from the acid which remains in excess.This body which is probably acetoxybenzamate of ethyl is very slightly soluble in cold water but tolerably soluble in hot water; from this solution it sometimes separates by cooling in the form of an oil which solidifies gradually on standing. If long boiled with water it regenerates acetoxybenzamic acid. It is very soluble in alcohol. On heating this substance to 100" in a Liebig's drying-tube in order to dry it for analysis a few drops of a colourless liquid which was scarcely soluble in water but miscible with alcohol and which greatly resembled carbolic acid in taste and smell condensed in the tube leading to the aspirator.As this liquid continued slowly to distil after the substance had been heated for many hours to looo the temperature was raised to between 130"and 135'. At this temperature the liquid distilled more rapidly and mas accompanied by a crystalline sublimate; at the same time the supposed acetoxybenzamate of ethyl rapidly became of a dark brown colour. Neither the liquid nor the sub- limate was obtained in sufficient quantity for further examination. Cahours* mentions a substance which he obtained by the action of chloride of benzoyl on oxybenzamate of silver but of which he neither gives the formula nor describes the properties. Hoping to obtain benzoyl-oxybenzamic acid I reacted on oxybenzamate of zinc with chloride of benzoyl.The product was an acid insoluble in cold water and in ether slightly soluble in boiling water in alcohol and in chloroform and resembling acetoxybenzamic acid in taste and in its appearance under the microscope. A determination of nitrogen by D u m as's process and the mean of two concordant combustions gave the following results :- Carbon . . 68.03 Hydrogen . . 5-12 Nitrogen . . 6.27 Oxygen . . 20.58 1oo*oo which differ too much from the calculated composition of benzoyl- oxphenzarnic acid ; nnmely-* Ann. Ch. Pharm ciii 90. This product is spoken of as glycobeiizamic acid in the Handw6rterbnch FOSTER ON ACETOXY BENZAMIC ACID. 24!3 Carbon .. 69.71 Hydrogen . . 4.56 Xitrogen . . 5.81 Oxygen . . 19.92 100*00 It is a matter of some interest to consider the relation in which acetoxybenzamic acid stands to hippuric acid and the nature of the isomerism of these two bodies. If we bear in mind the close analogy which exists between glycocol and oxybenzamic acid the formation of acetoxybenzsmic acid from chloride of acetyl and oxybenzamate of zinc is strictly comparable to the formation of hippuric acid from chloride of benzoyl and zinc-glycocol ; and its decomposition wheri heated with water in presence of a strong acid into acetic and osyben- zamic acids is analogous to the decomposition of hippuric acid into benzoic acid and glpcocol. C,H,OCl + C,N6ZnN0 = CgHgN30 + ZnCl Chloride of acetyl.Oxybenzamate of zinc. Acetoxybenzamic acid. C,H,OCl + C,H,ZnNO = CgHgNO + ZnC1 Chloride of benzoyl. Zinc-glycocol. Hippuric acid. CgKgNO3 + H,O = C,H,O + C,H,NO Acetoxybenzamic acid. Acetic acid. Oxybenzamic acid CgHgNO + H,O = C,H602 + C,H,NO Hippuric acid. Benzoic acid. Glycocol. Allowing for the difference between acetyl and benzoyl acetoxy- benzamic acid is to oxybenzamic acid what hippuric acid is to glycocol. The simplest way of expressing these relations in the formula? of the two substances is to write acetoxybenzamic acid as an acetyl-derivative of oxybenzamic acid (or as oxybenzamic acid in which an atom of hydrogen is replaced by acetyl) and ‘hippuric acid as a benzoyl-derivative of glycocol (or as glycocol in which an atom of hydrogen is replaced by benzoyl).Before we can give formulz which will indicate the further relations of these acids it is therefore necessary to consider the formulae of glycocol amid oxybenzamic acid. These two bodies occupy corresponding positions in two analogous series of compounds. R2 FOSTER ON ACETOXTBENZAMIC ACID. Acetic acid . C2H4O2 Benzoic acid C7H602 Chloracetic aci .d C2H,C102 Nitrobenzoic acid C,H (NOJO Glycocol . . C2H5N02 Oxybenzamic acid C7H7N02 Glycollic acid C2H*O3 Oxybenzoic acid C,H60 There are two principal points of view from which the members of the two series may be regarded and accordingly two principal. systems of rational formula by which they may be represented. We may on the one hand adopt formuh expressing only the genetic relations of the two sets of compounds to acetic and benzoic acids respectively; or on the other hand formula which express in addition the general nature of the differences which the various terms of each series exhibit in their relation to other substances.In the first case if we write acetic and benzoic acids as deriving from the type H20 we get- Acetic Series. Chloracetic acid . * C2H,,O) 0 Glycollic acid . C2R,(HHO)) 0 Benzoic Series. Berizoic acid Nitrobenzoic acid . Oxybenzamic acid . C7H4(H2N)0] 0 H L Oxybenzoic. acid In the second case we get the following or equivalent forrntih :- FOSTER ON ACETOXYBENZAMIC ACID. Acetic Series. Type.Acetic acid . . CHOJ .. 22Hio Elo Chloracetic acid Qlycocol * Glycollic acid . Benxoic Series. Benzoic acid . . CHO '*HI0 .. :lo Nitrobenxoic acid Oxybenzamic acid . Oxyhenzoic acid It will be seen that these two systems of formula3 differ in this that in the first set the type remains unchanged throughout but that the radicle is different in each compound; while in the FOSTEIl ON ACETOXYBENZAJIIC ACII). second set the type is variable but the radicle constant. It may perhaps be said that this difference is not essential but merely a difference of form the elements which in the one case are represented as replacing hydrogen in the radicles acetyl and beiizoyl and are written in the same line with the remaining elements of these radicles being in the other case separated and written above the other elements.Admitting this to he the case and supposing the two sets of formu18 to be used in the same sense the question arises whether or no one set of forrnuh is preferable to the other as a matter of form. On this point it may be observed first that the only consistent definition of a compound radicle is a group of elements contained in a greater or less number of substances and not altered by the reactions by which these substances are tramJ-bmed one iizto anof her and that it is therefore inconsistent to represent closely allied and mutually convertible substances as containing different radicles ; secondly that the only consistent iise of typical formuh is to express the nature of the tra?~~or~ut~ons which the bodies repre- sented by them are capable of undergoing and therefore that it is inconsistent to refer to the same type bodies of which the trans-formations are very different.For example the forniula+- Benzoic acid Nitrobenzamic acid Oxybenzarnic acid ought to imply that the salts of these three acids give similar products when acted upon by acid chlorides such as chloride of acetyl or chloride of benzoyl experiment however proves that the first two give anhydrides when so acted upon while the third gives a well characterized acid. The same difference .also exists between the salts of acetic acid and the salts of glycocol in respect to their behaviour with similar reagents. For these reasons the relations of glycocol and oxybenzamic acid to their congeners are most correctly expressed by the €armula3-and CHO 'H4 >' ol~cocol.Oxybenzamic acid. which represent them as amidic acids corresponding respectively to FOSTER ON ACETOXYBENZAMIC ACID. 247 giycollic (oxyacetic) acid and oxrbenzoic acid. Hence for hippuric and acetoxybenzamic acids we get the formule-Hippuric acid. Acetyl-oxybenzamic acid. (Benzoyl-oxyacetamic acid.) By way of justification of this discussion of what may seem very obvious formul~e I may perhaps be allowed to give a collection {probably far from complete) of formullx which have recently been proposed for glycocol hippuric acid and oxybeiizarnic acid. GI;LYCOCOL. HIPPURIC ACID.OXYBENZAMIC ACID. CLH302 N N{ : { q3 Gerhardt Trait6 iv 767 (1856). C14H5(H2x>04 Cahours Ann Ch. Phys. [3] liii (1858). Wislicen us Zeitschr. f. d. gesammt. Nsturwissenschaften xiv (1859) * W eltzien Zusnmmenstell. d. organ. Verbind. (1860)% * / * 4 I 4k /? C~H~HZ)O~ C,,FNHZP H }02 H ‘}O2 Borup-Besanez Lehrb. d. organ. Chemie ii (1860) * (‘2 { 2N) [c2’21’0 Ho’C&2 ;:{ { 2N) c202}Ec2’21,0 Ho*(‘12 { 2N) [c&021J0 Kolbe Ann. Ch. Pharm. csiii (1860). co Limpricht Lehrb. d. organ. Chemie (1860). * In the forrnnls marked with an asterisk 33:= 1 C 6 0= 8. 1= FOSTER ON ACETOXYBENZBMIC ACID. It is hardly necessary to add in conclusion that I make no claim to originality in reference to the formuh proposed in this paper.Gerhardt in the formula quoted above represented lrippiiric acid as benzoyl-glycocol and the formulz which I have adopted for oxybenzamic acid and glycocol were first proposed by Keliule' (Ann. Ch. Pharm. civ. 148; cvi. 150). Moreover the formulze for glycocol arid hippuric acid which are quoted from Limpricht are very nearly identical with those proposed in this paper The only difference is that in order to represent other reactions than those which are here taken into account he has divided the radicle C2H20 into CO and CW, and has consequently derived giycocol and hippuric acid from the type H5N1 ,which might perhaps be more correctly 890I ;for though in some compounds nitrogen is com-bined with the equivalent of five atoms of hydrogen these substances are always easily broken up into a group equivalent to H and a group equivalent to H,N Through the kindness of Professor ICekul6 of the University of Ghent I have been able to perform the experiments described in this paper in his laboratory.Ghent 19th Jzcne 18GO.