July, 1938
DERIVATIVES OF 4-AMINOBENZENESULFONANILIDE
A solution of the ene-diol in alcoholic ferric chloride produces a deep green-blue color which gradually fades to yellow on standing. Evaporation of this solution yields a light yellow solid, melting point and mixed melting point with the above 134” melting compound unchanged.
Summary Herein are reported the preparation aiid prop-
1(hNTRIRUTION
1553
erties of a new ene-diol having the ope11 chain -C=C-C-
I
1
OH OH
11 , and some further evidences of the
activating influence of the mesityl nucleus upon a-substituents together with its stabilizing effects on the resulting compound. WASHINGTON,
D.
c.
RECEIVED MAY10. 1938
FROM THE COLLEGE O F PHARMACY, UNIVERSITY OF ILLINOIS]
Derivatives of 4-Aminobenzenesulfonanilide. I BY G. L. WEBSTERAND L. D.POWERS We have prepared a series of derivatives of 4Following the observation made by Trefouel, Trefouel, Nitti and Bovet’ that 4 aninobenzene- aminobenzenesulfonanilide in which a hydrogen sulfonamide was a valuable therapeutic agent in atom of the anilide ring has been substituted with the treatment of infections caused by the P-hemo- a nitro, amino or hydroxyl group in the hope that lytic streptococcus, a large number of deriva- biological tests might disclose active chemotheratives and analogs of this compound were tested in peutic agents. Preliminary reports to us have indicated that the search for other compounds which would be effective against the same and other organisms. several of these compounds show some slight proBiological tests have shown only a few substances tective action against experimental streptococcal which have comparable action against bacterial infections in mice and one, 4-acetaminobenzenesulfon-4’-aminoanilide, has been described as modorganisms of any type. It has been shown by Buttle, Gray and Stephen- erately effective.6 A more detailed report will be son*and by Rosenthal, Bauer and Branham3that, published elsewhere by Dr. Long. Nitro derivatives of 4-acetaminobenzenesuIfonwhen given in equal molecular doses, 4-aminobenzenesulfonanilide is just as effective against anilide were prepared by the action of 4-acetpneumococcic infections in mice as is 4-aminoben- aminobenzenesulfonchloride on a hot solution of that the nitroaniline in dimethylaniline. zenesulfonamide. It has also been The corresponding amino derivatives were prethe presence of an amino group para to the sulfonamide group is necessary for therapeutic action. pared by the ferrous hydroxide reduction method Only a few derivatives of 4-aminobenzenesul- of Jacobs and Heidelberger.’ The hydroxyl derivatives of 4-acetaminobenfonanilide, in which an amino or a nitro group has zenesulfonanilide were prepared by the action of been substituted for a hydrogen atom of the ani4-acetaminobenzenesulfonchloride on a hot aquelide ring, have been reported in the literature. ous solution of the corresponding aminophenol Whitby4 has published results on the protective and also by the method used for preparing the action of the tartrates of 4,4’-diaminobenzenesulnitro derivatives. fonanilide and 4,3’-diaminobenzenesulfonanilide Preparation of derivatives of 4-aminobenzeneagainst experimental infections in mice and Bauer and RosenthaP have reported their results with sulfonanilide was accomplished by boiling the the first of these two diamines and with 4-amino- acetamino compounds with an alcoholic solution benzenesulfon-4’-nitroanilide. The authors of of hydrochloric acid. Diazotization of 4-acetaminobenzenesulfon-3’these papers presented no syntheses or chemical aminoanilide and heating the resulting solution characterization of these compounds. yielded the cortesponding 3’-hydroxy derivative. (1) Trefouel, Trefouel, Nitti and Bovet, Cowspl. rend. soc. b i d . , lPo,756 (1935). Diazotization of 4-acetaminobenzenesuIfon-4’(2) Buttle, Gray and Stephenson, Lancet, I , 1286 (1936). aminoanilide and boiling the diazonium solution (3) Rosenthal, Bauer and Branham, U . S. P u b . Health Refits., 61, 662 (19371. (4) Whitby, Lancet, 1 , 1517 (1937). (S) Baucr and Rosenthal, U . S. Pxb. H c i i l l k Regls., 63, 40 (1938)
(6) Private communication from Dt. Perrin H. Long. The Johns Ilopkins Hospital. ( 7 ) Jacohs and Heidellxrger, THISJ O U R N A L 39, 1435 (1017).
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