[CONTRIBUTION FROM
THB
CHEMICAL LABORATORIES OF COLUMBIA UNIVERSITY]
THE ANHYDRIDES OF N-ARYLANTHRANILIC ACIDS. I1 J. STEIGMAN
AND
G. POWELL
Received January 86, 1957
Compounds of unknown constitution, analyzing m anhydrides, have often been reported in dealing with anthranilic acids, salicylic acids, and related compounds1. While working with N-phenylanthranilic acid and N , N-diphenylanthranilic acid the authors observed that the action of benzenesulfonyl chloride on pyridine solutions of these acids did not lead to N-benzenesulfonyl derivatives of the acids, but to yellow anhydrides. These anhydrides were observed to give rise to acridones on heating, and to rearrange to compounds of a peptide type if a hydrogen atom was still available on the nitrogen for rearrangement. To the yellow anhydride, by virtue of its reaction with ammonia and alkalies, was acribed the acyl anhydride formula2, hitherto unrecognized among such amino-acids. The present communication describes further results with substituted N-arylanthranilic acids. The reaction appears to be a general one for N-arylanthranilic acids. Attempts have been made to obtain the peptide type of compound from N-arylanthranilic acids by other methods not involving the possibility of anhydride formation in the synthesis. These have been so far unsuccessful and the preparation of N-arylanthranoyl-N-arylanthranilic acids is at present limited to the method described above. EXPERIMENTAL
A . Acyl anhydride8 1. N-o-Ethoxyphenylanthranilicanhydride.-By the addition of benzenesulfonyl chloride to a pyridine solution of N-o-ethoxyphenylanthranilicacid. Crystallized from alcohol or by the addition of alcohol to a chloroform Rolution of the crude anhydride; m. p. 135"-137"; yellow needles. Anal. Calc'd: C, 72.55; H, 5.68; N, 5.64. Found: C, 72.70; H, 5.68; N, 5.5. 8. N-o-chlorphenylanthranilicanhydride.-Yellow needles melting near 170°, only ( a ) HELLERAND LAUTH,Ber. 62B, 2295 (1919). ( b ) SRALLINO, Guzz. chim. ital., 37, (11) 151 (1907). (c) MEYER,Ann., 361,267 (1907). 2 GOODMAN, ARBITER,AND POWELL, J . Am. Chem. Soc., 66,4294 (1933). 211 1
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slowly changed by treatment with acetic acid, but converted into a compound of the B type by heating for a short time with dilute alcoholic solutions of alkalies. Anal. Cdc'd: N, 5.87. Found: N, 6.08. 3. N-o-tolylanthranilic anhydride.-Yellow needles, m. p. 164'-166' (from alcohol). Gives an acridone and o-tolylanthranilic acid on heating to 190" for five minutes, and is converted into a compound of the B type by refluxing with acetic acid containing sodium acetate for a short time. Anal. Calc'd: N, 6.42. Found: N, 6.75. 4. N, N-di-o-tolylanthranilic anhydride.-Yellow needles, m. p. 188'-191". Givee no compound of the B type on treatment with acetic acid, and is hydrolysed by alcoholic alkalies. 6. N-mesitylanthranilic anhydride.-N-mesitylanthranilic acid was prepared, and the yellow anhydride was obtained in the usual way; m. p. 200'C-203".
B . Compounds of the Peptide Type 1. From N-o-ethoxyphenylanthranilic anhydride by treatment with glacial acetic acid; colorless; m. p. 188-190'. Soluble in dilute ammonia. Anal. Calc'd: C, 72.55; H, 5.68; N, 5.64. Found: C, 72.57; H, 5.74; N, 5.5. 2. From N-o-tolylanthranilic anhydride in the same manner; colorless; n p. variable; probably not pure. 3. From N-o-chlorphenylanthranilic anhydride by heat with alcoholic alkalies for a short time; colorless; m. p. near 225" with decomposition.
.
SUMMARY
The preparation of substituted N-arylanthranilic anhydrides is d e scribed. The reaction appears to be a general one for N-arylanthranilic acids.
