GB1132318A - New substituted phenylacetic esters, their production and compositions containing them - Google Patents

Abstract

1,132,318. Phenylacetic esters. J. R. GEIGY A.G. 29 March, 1967 [30 March, 1966], No. 14261/67. Heading C2C. New phenylacetic esters of the general formula (wherein R 1 , R 2 and R 4 each represent a C 1-4 alkyl or alkoxy group, a halogen atom up to atomic number 35 or a CF 3 group, or R 2 and R 4 may also represent H, R 3 represents H, a C 1-4 alkyl or alkoxy group or a halogen atom up to atomic number 35, R 5 and R 6 represent H, C 1-5 alkyl groups or benzyl groups, and R 7 represents a C 1-6 alkyl group or an aralkyl group with up to 3 carbon atoms in the alkylene portion) are prepared from the corresponding acid by known esterification methods, raised temperatures being avoided when the reaction medium is acid. Methods specified are reaction of the free acid with a diazoalkane in an inert organic solvent, with a 1,1-dialkoxy- or -diaralkoxy-trimethylamine in an inert solvent, with an alkanol or arylalkanol in the presence of 1,1-dineopentyloxytrimethylamine, or, at temperatures not above - 5‹ C., with an alkanol or arylalkanol and SOCl 2 , and reaction of a salt of the acid with an alkyl or aralkyl halide, sulphate or sulphonate. Phenylacetic acids employed as starting materials are prepared by the following processes: (1) hydrolysing the correspondingly substituted 1-phenyl-2-indolinones, which in turn are prepared as follows: (a) when R 5 and R 6 are H or R 5 is C 1-5 alkyl and R 6 is H, reacting an appropriately substituted diphenylamine with a 2-chloroalkanoyl chloride and heating the resulting 2 - chloro - N - phenylalkanoanilide with AlCl 3 ; (b) when one or both of R 5 and R 6 is or are C 1-5 alkyl or benzyl, converting a corresponding 1-phenyl-2-indolinone in which R 5 = R 6 = H to its mono- or di-Na compound by reaction with NaH or NaNH 2 in dimethylformamide and reacting the product with the corresponding amount of a C 1-5 alkyl or benzyl halide; (c) when R 5 is benzyl and R 6 is H, condensing a 1-phenyl-2-indolinone in which R 5 = R 6 = H with benzaldehyde and hydrogenating the resulting 1-phenyl-3-benzylidene-2-indolinone; (2) reducing a low alkyl ester of an appropriate N-phenylanthranilic acid to a substituted o-anilinobenzyl alcohol, boiling this with acetyl chloride to form a substituted α-chloro- N-phenyl-o-toluidine or a substituted α-chloro- N-phenylaceto-o-toluidide (depending on the nature of the substitution in the phenyl group), reacting the product with NaCN or KCN and hydrolysing the resulting α-cyano compounds. The preparation of the following starting materials is also described: 2,6-dichloro-N- phenyl - m - toluidine; 2,6 - dichlorodiphenylamine; N - (2,6 - dichlorophenyl) - acetanilide; 2,6,41 - trichlorodiphenylamine; N - (p - chlorophenyl) - 2,6 - dichloro - m - toluidine; 2,6 - dichloro - N - (p - methoxyphenyl) - m - toluidine. Therapeutic preparations for the treatment of inflammatory diseases comprise the esters of the general formula above in combination with an inert carrier and, optionally, further additives.