GB1353499A - Substituted phosphoramide compounds and their conversion to substituted benzamide derivatives - Google Patents

Abstract

1353499 Preparing substituted benzamides; substituted phosphoramides SOC D'ETUDES SCIENTIFIQUES ET INDUSTRIELLES DE L'ILE-DE-FRANCE and TEIKOKU CHEMICAL INDUSTRY 20 Dec 1971 [21 Dec 1970] 59101/71 Headings C2C and C2P A substituted benzamide of the formula in which A is a C 1 -C 5 alkylene group, X is H or halogen, R 3 is H, OH or C 1 -C 5 alkoxy and R 1 and R 2 are each C 1 -C 5 alkyl, or salt thereof, is obtained by reacting a substituted benzoic acid of the formula: with a novel phosphoramide compound of the formula: or a salt thereof. The reaction is suitably effected by heating the reactants at 50-150‹ C. in an inert solvent and when the phosphoramide is used in the form of a salt, e.g. the hydrochloride, the product I is also obtained in the form of a salt. Examples are given for the production of substituted benzamides of Formula I in which (a) R 1 and R 2 are each ethyl, X is Cl and R 3 is OCH 3 and OH respectively, (b) R 1 and R 2 are each ethyl and R 3 and X are each H, the product being obtained directly as the hydrochloride by using the phosphoramide in the form of its trihydrochloride and (c) R 1 and R 2 are each ethyl, R 3 is methoxy and X is Br. When R 3 in the product I is OH the product can be converted to the corresponding compound in which R 3 is alkoxy and in one example 2 - methoxy - 4 - amino - 5 - chloro- (N,N-diethylaminoethyl) benzamide is obtained by treating the corresponding 2-hydroxy compound with dimethyl sulphate. Also, when X is H in the product the latter may be converted to the corresponding 5-chloro compound by treatment with a suitable chlorinating agent, e.g. phenyliodine dichloride, iodine trichloride or succinic imide chloride. The products have pharmacological activity. The novel phosphoramides of Formula III are obtained in the form of their trihydrochloride salts by reacting an appropriate N,N- dialkylene diamine, e.g. diethylethylene diamine, with phosphorus oxychloride and the resulting salt can be converted to the free base by adding an alkali to the trihydrochloride salt. 2 - Hydroxy - 4 - amino - 5 - chlorobenzoic acid is obtained by reacting p-aminosalicylic acid with an appropriate chlorinating agent, e.g. phenyl iodine dichloride, iodine trichloride, succinic imide chloride, or cyanuric chloride.