DERIVATIVES OF CAMPHOROXALIC ACID.
I499
point could not be changed by further recrystallization. The compound is soluble in boiling water, hot alcohol or boiling chloroform. but dissolves in ether with difficulty. Found: N, 31.64. Calculated for C,H,N,: N, 31.58.
DERIVATIVES OF CAMPHOROXALIC ACID. XIII.’ B Y J. BISHOP TINGLE A N D S. J. BATES.
Received September
IO,
xgxo.
In some of the earlier papers on this subject i t has been pointed out that the condensation compounds of camphoroxalic acid and of its esters (2 : CC0,H (alkyl) with amines may be formulated either as C,H, [ I or CO NHR 1
1.
CHCC0,H (alkyl)
. C(0H)- group in the condensation compound? Our first experiments were carried out with phenylcamphoformeneC : CC0,H aminecarboxylic acid, C,H, ; it is prepared very readily from C(NHC,H,)CO,H,
the former of which then yields
the quinine. The only product which could be obtained by the action of phosphorus trichloride on phenylcamphoformeneaminecarboxylic acid was camphoroxalic acid. Phosphorus pentachloride reacts like the trichloride, ultimately, therefore, the reaction may be expressed as one of simple hydrolysis of the CN linkage. A considerable number of experiments were made, under varying conditions, on the interaction of methyl sulphate and phenylcamphoformeneaminecarboxylic acid. I t was, of course, to be expected that a methyl group would replace the hydrogen of the carboxyl, so giving the methyl ester, but we hoped that, in addition, the hydrogen of the -NHC,H, (formula I) might be substituted, thus giving the compound
C : CCO,CH, C,H,,(
I 1 /CH, .
This would afford direct evidence in favor of
CON
‘CJh the formula in question. Unfortunately, this double substitution could not be realized, the only product which we could obtain was methyl phenylC : CCO,CH, campho~ormeneantznecarboxylate,C,H,,’ 1 I . I t is deposited in \CONHC,H, yellow crystals, melting a t 1 2 7 ~ . Under the varied conditions of our experiments it does not react with methyl sulphate. We failed to obtain any reaction between methyl sulphate and phenyl S! : CH camphoformeneamine, C8H,,’ I 1 . These results, apart from \CONHC,H, - other evidence, appear, therefore, to decide effectively against any formula : C(OH)CO,H such as C8H, , for the condensation products of camC:NR phoroxdic acid and amines.
(j!
DERIVATIVES OF CAMPHOROXALIC ACID.
15PI
Methyl sulphate and carnphoroxalic acid give the methyl ester. Qn one occasion, by the further action of the sulphate, this ester yielded a small quantity of what appears to be methyl methoxycamphoroxalGte, C : C(OCH3)C0,CH, . Hitherto we have not succeeded' in obC8Hl4' I
'co
taining this substance in quantity sufficient for adequate study. Attempts to obtain compounds from nitrous acid and phenyl camphoformeneaminecarboxylic acid, carnphoroxalic acid, or its ethyl ester were unsuccessful. We employed sodium nitrite and also amyl nitrite, under varied conditions. Camphoroxalic and thiosemicarbazine react readily in hot alcohols more slow& a t the ordinary temperature, to form thzosemicarbazylcamC , : CCO,H phoformeneaminecarboxylic acid, C,H 1 1 ; in benzene, 14\CONHNHCSNH, the combination occurs much more slowly at the boiling point of the solution and is inappreciable a t the ordinary temperature. The acid exists in two modifications which melt a t 120-5 O and '+go, respectively. The lower melting form (A) is the more readily soluble in benzene, i t is somewhat viscid and is produced by adding hydrochloric acid to an aqueous solution of the sodium salt of the carboxylic acid. It is also formed by recrystallizing the higher melting modification (B) from water. I t changes slowly a t the ordinary temperature, more rapidly when heated alone or with benzene, to the (B) form. A mixture of (A) and (B) melts a t 140-5O. The modes of formation of (A) and (B) suggest that the former is an unstable hydrate of the latter. From the nature of the case it is impossible to determine this fact with certainty. There are also the possibilities of cis- and tram-isomerism, C8HM C8HM A A
c.co I1
-
0c.c
I1 H,NCSNHNHCCO,H + H,NCSNHNHCCO,H and of tautomerism, C , : CCO,H /CHCCO,H C"H1, I I1 to be considered. C8H14\ I I CONHNHCSNH, 'TONNHCSNH, Our chief object in preparing thiosemicarbazylcamphoformeneaminecarboxylic acid was to compare its'behaviar with the similar derivative of semicarbazine,' i. e., to determine the effect of exchanging an oxygen for a sulphur atom. The contrast between the two compounds is most marked in the relative readiness with which they form closed chain derivatives. Whereas semicarbazylcamphoformeneaminecarboxyiic acid, Bishop Tingle and Robinson, LOC.c i t .
I 502
ORGANIC AND BIOLOGICAI,.
C , C*"
: CC0,H
I I
undergoes further condensation without diffi'TONHNHCONH, culty, the thio derivative exhibits comparatively little tendency to change in this direction. When fused, a portion of the acid is recovered and the remainder is converted into resinous products. Absolute alcohol and dry hydrogen chloride give only ethyl thzoseirzicnrbaz3ilcamphojormenearnzn&C : CCO,C,H, carboxylate, C,H,,/ 1 1 which is deposited from benzene \CONHNHCSNH, in white crystals, melting a t 150-1 ". Thiosemicarbazylcamphofornieneaminecarboxylic acid is dehydrated by the action of acetic anhydride, quickly a t about IOO", more slowly a t the ordinary temperature. The yield is almost quantitative and the compound is deposited in bright red crystals, melting a t 181-2'. IVhen treated with a warm aqueous solution of potassium hydroxide or a boiling aqueous solution of sodium carbonate the parent acid is regenerated. These reactions make us inclined to regard the conipound as being thioC :C-CO-NH semicarbazylcamphoformenearninecarboxj~lactzrnzde, C,H,,(/ 1 ' , \CO~-H.NH.CS, its deep color, which appears to be characteristic of the compound itself and not due to traces of ferric thiocyanate, suggests that it probably c : c-co-N exists in a tautomcric form, such as C,H,/l I ii or \CONH.NH .CSH C : C.C(OH) :N C&M\ / I I I ' CONH . NH . CS Acetic anhydride, to which a few drops of conc. sulphuric acid have been added, hydrolyzes thiosemicarbazylcamphoformeneaminecarboxylic acid to thiocyanic acid, the presence of which was shown by means of a ferric salt, and aminocamphoformenearninecarboxylic acid, which latter then condenses to camphylpyrazolecarboxylic acid (in. p. 261-2 "), ,C : CCO,H C : CCO,H C 8 " \ I I -+HSCN+ C8H14< 1 [ + CONHNH CSNH, CONHNH, C - CCO,H C,H,,( I / I! .C N )
~
1
\/
NH The identity of this pyrazole derivative with that prepared from camphoroxalic acid and hydrazine, or semicarbazine by Bishop Tingle and Robinson,' was shown by direct comparison, Our acid melted a t 261-2', Am. Chem. I., 36, 259.
DERIVATIVES OF CAMPHOROXALIC ACID.
1.503
whereas the melting point observed previously was 255-8'. The difference is undoubtedly due to variation in the rapidity of heating, because the carboxylic acid evolved carbon dioxide a t a temperature below its melting p0int.l A slight modification of Bishop Tingle and Robinson's process for the preparation of camphylpyrazolecarboxylic acid is described in the experimental portion of this paper (vide p. 1511). Only resinous products could be obtained by the action of concentrated sulphuric acid alone, a t the ordinary temperature, on thiosemicarbazylcamphoformeneaminecarboxylic acid. We propose to make a further examination, under other experimental conditions, of the ability of this carboxylic acid to form cycloids containing sulphur. I n the hope of obtaining material suited for further investigation, we have examined the interaction of camphoroxalic acid with a number of amines. With I ,3,4-xylidine it gives r1g,4-xylidine1,3,4-xylidylC : CCO,NH,C,H,(CH,), camphoformeneaminecarboxylate, C,H li' 1 1 , which \CO NHC,H,(CH,), is deposited in brown crystals, melting a t 93-4'. By the action of sodium carbonate, followed by hydrochloric acid, on this salt, 1,3,4-xylidyl,C : CCO,H camphoformeneaminecarboxylic acid, C , is produced. The acid is deposited in yellow crystals, melting at 117-8'. C , : CH The third member of the series, the amine, CBH,, I 1 \co NHC,H,(CHJ,' is probably formed a t a temperature above the melting point of the acid, but i t could not be isolated in a crystalline condition. Comparing these compounds with the corresponding derivatives of aniline, it is evident that they crystallize with greater difficulty and are, therefore, less suited for our projected investigations. p-Chloroaniline and camphoroxalic acid combine readily to form ,C : CC0,H p-chlorophenylcamphoformeneaminecarboxylic acid, C,H,,( I I co NHC,H,CI' which was obtained in yellow needles, melting a t 182-3'. I t s crystallizing power is considerable. With a larger proportion of p-chloroaniline it failed to form a p-chloroaniline salt, although possibly one could be obtained at a low temperature. When camphoroxalic acid and 9-chloroaniline are heated gradually up to 155-6oo,without a solvent, carbon dioxide is evolved and p-chlmo-
' L O C cit.
f
SO4
ORGANIC AND BfOLOGfCAL.
,c: 1
CH
1 , is produced. It is C 'O NHC,H,Cl also formed by heating p-chlorophenylcamphoformeneaminecarboxylic acid above its melting point. The amine is deposited in white crystals, melting a t 194-jo. Dibenzylamine and camphoroxalic acid react quickly, in equimolecular proportion, to form an additive compound. I t gives an intense reddish purple color with an alcoholic solution of ferric chloride and is resolved somewhat slowly into its constituents by the action of an aqueous solution of sodium carbonate, or by hydrochloric acid. I n spite of the slowness of this decomposition, we regard the substance as being dibenzylC : C(OH)CO,NH,(CH,C,H,), , rather than amine camphoroxalate, C,H,, fihenyZcam@ojormeneamine, C,H,,
