Patent GB-984120-A (GB)
Title: Anthranilic acid derivatives and methods for producing same
IPC: C07C/
Filed: 1961-06-22
Abstract: The invention comprises compounds of the general formula <FORM:0984120/C2/1> (wherein R1 represents a chlorine atom or a methyl group and R2 a chlorine atom or a methyl or ethyl group, R2 being chlorine when R1 is methyl) and their salts, and the preparation thereof by condensing a benzoic acid derivatives of the general formula <FORM:0984120/C2/2> with a compound of the general formula <FORM:0984120/C2/3> (wherein Y and Z are different and represent -NH2 or a halogen atom and M represents hydrogen or a metal) or by hydrolysing (preferably under alkaline conditions) an N-acyldiphenylamine of the general formula <FORM:0984120/C2/4> (wherein Acyl represents an acyl radical, especially an optionally substituted benzoyl radical, and R represents a carboxyl group or a group hydrolysable thereto).  N-Acyldiphenylamines of the last general formula above may be prepared as follows: (a) by reacting an anilide of the general formula <FORM:0984120/C2/5> (wherein R3 represents a tertiary alkyl group or an optionally substituted aryl radical) with phosphorus pentachloride to produce a benzimidoyl chloride of the general formula <FORM:0984120/C2/6> which is then reacted with an o-R4-phenol or alkali metal phenate (where R4 is a cyano, carboxy, alkoxycarbonyl, aryloxycarbonyl, aralkoxycarbonyl or carbamido group) to form an imido-ester of the general formula <FORM:0984120/C2/7> from which the desired compounds is formed by thermal rearrangement; (b) (when R = CN) by treating an N-acylaniline of the general formula <FORM:0984120/C2/8> with thionyl chloride to obtain an iminochloride of the general formula <FORM:0984120/C2/9> which with an alkali metal salt of a phenol of the general formula <FORM:0984120/C2/100> yields an imido-ester of the general formula <FORM:0984120/C2/111> from which again the desired compounds is obtained by thermal rearrangement; (c) (when R = COOH and neither R1 nor R2 is an oxidizable substituent) by oxidizing a compound of the general formula <FORM:0984120/C2/122> (wherein R6 represents a radical oxidizable to COOH and Ar an o-chlorophenyl group containing non-oxidizable R1 and R2 substituents); (d) (when R is a carboxylic halide group) by treating the corresponding acid (R = COOH) with a halogenating agent.  2 - Methyl - 3,6 - dichloroaniline is prepared by brominating 2-methyl-3-chloroacetanilide in the 4-position, chlorinating the product in the 6-position, and removing the bromine atom by catalytic hydrogenolysis and the acetyl group by acid hydrolysis.  2,6 - Dichloro - 3 - ethylaniline is prepared analogously from 3-ethylacetanilide, using two molecular proportions of chlorine in the chlorination step.  Pharmaceutical preparations, having antiinflammatory activity and suitable for heating rheumatic symptoms, comprise the compounds of the first general formula above, or their salts (e.g. alkali and alkaline-earth metal, ammonium, choline and mono-, di- and tri-ethanolamine salts), together with a solid or liquid carrier or diluent. They are preferably in forms suitable for oral administration, e.g. tablets, capsules, powders, dragees, suspensions or solutions.