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The data further require that the benzainide nucleus of I11 have the three hydroxyl groups a t tlie 2, 3 and 6 positions with the y-(P-[4-chloro-7hydroxy-3-methylphthalide-3 ])-butyricacid radical a t position 4. Position 5 is free for ring closure i!i the formation of IV. C. W. WALLER
1-01. 7-1
solution is decreased when a carboxamide group is located on the central carbon of a P-diketone system.' The presence of this added chromophore and the acidic function a t pKa 7.2 suggests that an isolated cyclic P-diketone is present in I. The infrared bands in the 6 to 7 p region substantiate this conclusion. LEDERLE LABORATORIES DIVISION B. L. HUTCKISCS When aureomycinic acid, I, is further treated AMERICASCYANAMID COMPANY A. A. GOLDMAS with 3 N sodium hydroxide (in the absence of PEARLRIVER,XEWYORK C. F. WOLF R. 1%'. BROSCHARD reducing agents), dimethylamine and desdimethylJ. H , ~VILLIAMS aureornycinic acid is formed. This elimination of dimethylamine with the introduction of a double RECEIVED SEPTEMBER 15, 1953 bond readily explains the formation of the aromatic group, 2,3,6-trihydroxybenzamide,of desdimethylaminoaureomycinic acid.2 The placing of diDEGRADATION OF AUREOMYCIN. V. methylamine in the 5 position of the cyclohexaneAUREOMYCINIC ACID dione ring makes possible the ,&elimination of this Sir: group when a trace of oxygen forms the a-diketone, When aureomycin is treated with 5 N sodium 111, from I. hydroxide containing a reducing agent, a- or paureomycinic acid, I, is formed. With sodium CHI CH? hydrosulfite and a reaction time of 2.5 hours a t room temperature a-aureomycinic acid, m.p. 225230' for the hydrochloride, [ a I z 5 D 4-54' (dilute hydrochloric acid), anal. Calcd. for C22H26N2ClOs.HC1: C, 49.53; H, 4.88; N, 5.25; C1, 13.32; C-CH3, 2.82. Found: C, 49.38; H, 5.20; N, 5.34; il li C1, 13.58; C-CH3, 2.54, is obtained. If the reac0 0 tion time is increased to four days, P-aureomycinic 111 Iv acid, map. 174-185' (dec.) for the hydrochloride, [CY]% - 10.2' (dilute hydrochloric acid), anal. Calcd. as for the a-isomer. Found: C, 49.G0; H, 5.62; N, 5.23; C1, 13.35, is isolated. The pIfO--j)j-CONH~ . isomer also results if zinc dust is used in lieu of I hydrosulfite and the reaction mixture is heated OH for two hours on the steam-bath. A free carboxyl group in I is indicated by the The final step in the reaction shows the o-quinone, facile formation of a monoester, anal. Calcd. for TV, acting as a hydrogen acceptor for the oxidation C21H24NzC107COOCH3~HC1 : OCH3, 5.68. Found : of another molecule of I. If more than a trace of OCH3, 5.11, with methanolic hydrogen chloride. oxy en is present, further changes are initiated. T e formulation of the structure of aureornycinic The preparation of the monomethyl ester monomethyl ether, 11, of I with diazomethane or meth- acid as V is consistent with the chemical and physisulfate and sodium carbonate and the subsequent cal data. oxidation of I1 to the half ester of p-(d-chloro-7C,Hs 5H3 methoxy-3-methylphthalide-3)-glutaric acid con\ / CI CH? S firms the presence of a carboxyl group in I. The lactone band a t 5.7 p in the infrared spectra of I establishes the presence of the phthalide nucleus. Similarly, the ultraviolet absorption spectra of I and I1 clearly show the presence of a phthalide moiety. The titration curve of I, in addition to showing the acid functions due to the carboxyl and 7hydroxyphthalide, demonstrates the presence of an Aureoniycinic Acid acid function of pKa 7.2. Subtraction of the ultraviolet absorption specB. L. HUTCHISGS tra of P-(4-chloro-7-methoxy-3-methylphthalide-3)-LEDERLE LABORATORIES DIVISIOX C. LV. ~ Y A L L E R R. 1V. BROSCHARD COMPATY glutaric acid from those of I, gives spectra with AMERICANCYAXAMID C. F. WOLF RIVER,~ E YORK W absorption maxima a t 282 mp ( E 15,500) in 0.1 N PEARL P. W. FRYTH sodium hydroxide and a t 267 mp ( E 15,400) in 0.1 N J. H. WILLIAMS hydrochloric acid. The spectra of this added RECEIVED SEPTEMBER 5, 1952 chromophore compares favorably with those of (1) For comparison of 1,3-cyclopentanedione with that of 3.4dimedone which has maxima a t 282 mp ( E 23,700) in 0.1 N sodium hydroxide and a t 260 mp ( E 14,- dihydroxy-2,5-dioxocyclopentane-l-carboxamidesee C. W. Waller, L. Hufchings, C. F. Wolf, R.W. Broschard, A. A. Goldman and 000) in 0.1 N hydrochloric acid, except the ex- JH.. H. Williams, THISJOURNAL,74, 4078 (1952). tinction coefficient of dimedone in alkali is greater. (2) C. W. Waller, B. L. Hutchings, A. A. Goldman, C. F. Wolf, 'fhc. molecular extinction coefficient in alkaline K . XV. Broxhard and J. H . Williams, ibid., 74, 4970 (1952).
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