Patent GB-1139332-A (GB)
Title: Substituted phenylacetic acids and processes for their production
IPC: C07D209/38
Filed: 1966-04-07
Abstract: 1,139,332. Amino-phenylacetic acids and their salts. J. R. GEIGY A.G. 7 April, 1966 [8 April, 1965], No. 15497/66. Heading C2C. [Also in Division A5] The invention comprises substituted aminophenylacetic acids of the general formula wherein R 1  represents a C 1-4  alkyl or alkoxy radical, a halogen atom up to the atomic number 35 or the trifluoromethyl group; R 2  and R 3  each represent hydrogen, a C 1-4  alkyl or alkoxy radical or a halogen atom up to atomic number 35, R 4  represents hydrogen, a low alkyl or alkoxy radical, a halogen atom up to atomic number 35 or the trifluoromethyl group, and R 5  and R 6  each represent hydrogen, a low alkyl radical or a benzyl radical, and their salts with inorganic and organic bases. The novel compounds may be made by heating a compound of the general formula with an alkali metal hydroxide or carbonate or an alkaline earth metal hydroxide and, if desired, liberating the acid from the salt. Alternatively, a compound of general formula wherein A represents hydrogen or a carboxylic acyl radical, and R 7  represents a C 1-4  alkyl, or aralkyl, particularly benzyl, radical, is heated with an alkali metal hydroxide, carbonate or bicarbonate, an alkaline earth metal hydroxide or a basic ion-exchanger, or if R 7  is the benzyl radical, splitting this off by catalytic hydrogenolysis. As a further alternative, a compound of general formula is heated with an alkali metal hydroxide in an aqueous solvent. The 1-aryl-2-indolinones (II) are also novel and may be made by chloracetylating corresponding unsymmetrically substituted diphenylamines to form substituted 2-chloro-N-phenyl acetanilides and heating the latter with aluminium chloride. The radicals R 5  and R 6  can be introduced by alkylation with an alkyl halide or dialkyl sulphate or an aralkyl halide. A benzyl radical may be introduced by reaction with benzaldehyde and reduction of the benzal so formed. Compounds of Formula II where R 5  is low alkyl and R 6  is a hydrogen atom are made by reacting α-halogen alkanoic acid halides with substituted diphenylamines and then closing the ring. Compounds of Formula II are also obtained by saponification of compounds of Formulµ III and IV whereby ring closure occurs. Compounds of Formula III are obtained by converting the corresponding cyano compounds into imino-ether hydrochlorides and decomposing these with water. They can also be made by treating acids of Formula I with diazo alkanes or dialkyl sulphates, or with an aralkyl alcohol and N,N-dimethyl formamide neopentyl acetal, or with thionyl chloride at - 10‹ C. in abs. alkyl or aralkyl alcohol. Compounds of Formula IV are made by reacting α-halogen-N-aryl-o-toluidines or toluidides with sodium or potassium cyanide. α-Chloro-otoluidines or toluidides are made from o-arylamino-benzyl alcohols by boiling with acetyl chloride. The o-aryl-amino-benzyl alcohols are made by reduction of N-aryl-anthranilic acid alkyl esters with lithium aluminium hydride in ether or tetrahydrofuran, sodium borohydride in methanol or sodium borohydride and lithium bromide in diglyme. Diphenylamines substituted by R 1  to R 4  can be made by decarboxylating corresponding o-anilinobenzoic acids, or by reacting a substituted acetanilide with an R 4 - substituted bromobenzene. The substituted acetanilides are made by reacting the appropriate substituted aniline with acetyl chloride in glacial acetic acid.