COMMUNICATIONS TO THE EDITOR
3710
VOI. 74
vanadium(II1) ions. The possibility of rapid sepa- and K’ = groups as shown in Table I. These ration-induced exchange brought about when the phthalides can be degraded to phthalic or benzoic reaction mixture is added to alcoholic ala‘-dipyri- acid derivatives to prove the position of the chlorine dyl is not excluded by these observations. Dod- atom as indicated in the previous paper. 4-Chloro-7-methoxy-3-rnethyl-phthalide (111) son’s work with the iron(I1)-iron(II1) exchange showed exchange half-times of the order of 15-50 was prepared from 2-amino-3-methoxyacetopheseconds with the reactant species a t ca. 0.001 f none3by reducing the ketone to the alcohol and reeach. Reduction of the concentrations of the placing the amino by a cyano group. On hydrolyvanadium reactants may slow the observed rapid sis, I1 was formed which was chlorinated to 111 exchange rate to a point where kinetic studies with chlorine in acetic acid or with sodium hypocould be undertaken, but the techniques used so far chlorite and hydrochloric acid. 4-Chloro-3-hydroxy-7-methoxy-3-methylphthahave not permitted this because of difficulties with oxidation of both vanadium species in solutions at lide (V) was prepared by replacement of the amino by cyano in 2-amino-3-methoxyacetophenone, hyhigh dilution by traces of oxygen present. I V and chlorination to V. Both IV and drolysis to DEPARTMENT OF CHEMISTRY UNIVERSITY OF CALIFORNIA ~VILLIAM R. K I N G , J R . 1’probably exist in equilibrium with the correspondLos ANGELES 24, CALIFORNIA CLIFFORD S. GARNER ing o-carboxyacetophenonestructure and both will RECEIVED JUNE 6, 1952 form “normal” esters with diazomethane and “pseudo” esters with acid-methanol or acid chloride-methanol procedures. SYNTHESIS OF DEGRADATION PRODUCTS OF AUREOMYCIN
4-Chloro-7-methoxy-3-methyl-3-phthalidecar-
Sir : The synthesis of several degradation products‘ of Aureomycin by unequivocal methods has been accomplished. In each case these synthetic products were compared with the degradation products by means of m.p., mixed m.p., ultraviolet and infrared absorption spectra, and other properties to prove their identity. PITO.
I1 I11 IV
V VI
VI1 VI11 IX
R
R‘
H
-H
C1
-H
H
-OH -OH
c1
M.p., “C.
73-75 113-14 164-65 204-206
--C
boxylic acid (VII)was prepared by adding hydrogen cyanide to 2-cyano-3-methoxyacetophenone,hydrolysis of the product to VI and chlorination to VII. The compound was resolved by crystallizing ~ (1.2% in the brucine salt from water; [ a ] ” f25” ethanol). 3-(4-Chloro-7-methoxy-3-methylphthalidyl) -succinic acid (IX) was prepared by treating I V with
TABLE1 I1
Theory OCHi
07.4 50.5 61.8 52.4
5.6 4.2 5.2 3.9
H C1 H
-COOH -COOH -CH*COOH
168-70 199-200 207-209.5
59.5 51.5 57.1
4.5 3.5 4.8
c1
-CH&OOH CHnCOOH
209-210.5
51.1
4.0
I
-
CI
16.7 16.0 15.5 13.8 10.5 10.8
7
Found OCHI
C
H
66.9 57.0 62.1 52.3
6.0 4.6 5.9 3.9
59.8 51.7 57.3
5.2 3.9 5.2
51.4
4.4
T
C1
16.3 16.4 15.4 13.8
9.7 10.9
I
CHzCOOH
The first of these products is 6-chloro-3-methoxy- phosphorus pentachloride to form the “pseudo” phthalic anhydride (I) which definitely places the acid chloride which reacted with sodio diethyl carposition of the rnethoxyl and chloro groups in rela- bethoxysuccinate. Hydrolysis and decarboxylation to the other 2 substituents on the benzene ring. tion yielded VI11 which was chlorinated to IX. This compound was prepared from 3-methoxy-6- Two racemates resulted and the higher melting one, chloroanthranilic acid2by replacement of the amino m.p. 228-229’ with gas, was resolved by crystallizgroup by a cyano group through a Sandmeyer re- ing the brucine salt from ethanol; m.p. 209-210.5’ action and hydrolysis to the phthalic acid deriva- with gas; [ c y I z 6 ~- 2 0 . 4 O (5y0in alcohol). tive, m.p. 187-188’. Anal. Calcd. for C9H~04C1: (3) J. C.E. Simpson, el d.,J . Chcm. S O L . 646 (1945). C, 50.8; HI 2.4; C1, 16.7. Found: C, 51.5; H, S. KUSHNER CONTRIBUTION FROM THE JAMES H. BOOTHE 2.7; C1, 16.7. LEDERLELABORATORIES DIVISION JOHNMORTON I1 The remaining compounds are phthalides of the AMERICAN CYANAMID COMPANY JOSEPH PETISI following general formula in which R = chlorine PEARLRIVER, N E W YORK J . H. WILLIAMS RECEIVED JUNE23, 1952
OG
sir:
OCHs
I
11-IX
ol., T E I E J O m N a L . 74, 3710 (1962). (1) E. 1.B d w , rl ol., 1.Or#. C h m . , l?,180 (leS1).
(1) B. L. Htttchbg6,
81
DEGRADATION OF AUREOMYCIN
I n a preliminary report’ certain of the physical and chemical properties of aureomycin were out(1) R. W. Bro-rd, A. C. Dornbuah, S. Gordon, E. L. Hutchias, A. R.Kohl-, 0. Krupka, S,Kushner, D.V. Lcfemine and C.Pidacks. Sckncr, lW,199 (1949).
