GB1012235A - Phthalimide derivatives - Google Patents

Abstract

The invention comprises compounds of the formula <FORM:1012235/C2/1> where R1 represents a chlorine or fluorine atom or a methyl group and R2 represents an alkenyl, alkynyl, haloalkyl, hydroxyalkyl, sulphoxyalkyl, acyloxyalkyl, cycloalkyl or cycloalkyl-alkyl group, the cycloalkyl group being unsubstituted or having as substituents one or more halogen atoms, hydroxy and alkyl groups wherein the alkyl, alkenyl and alkynyl radicals have 1-6 carbon atoms and cycloalkyl groups have 5 to 8 carbon atoms, and the preparation thereof by (a) reacting a phthalimide of the formula <FORM:1012235/C2/2> where M represents an alkali metal ion; with a reactive ester of the formula R2X where X represents the acid residue of a reactive ester, preferably in a polar non-hydroxylic organic solvent at between 60 DEG C. and the boiling point of the solvent; (b) by heating a phthalimide of the formula <FORM:1012235/C2/3> with an equivalent of a primary amine R2NH2 in an inert organic solvent medium, preferably an alcohol, a benzene hydrocarbon or a halogenated hydrocarbon, until ammonia is no longer evolved; (c) by heating a phthalimide of the Formula (III) with a carbonate of a dihydroxyalkane or an alkylene oxide; (d) by heating a phthalic anhydride of the formula <FORM:1012235/C2/4> with a primary amine R2NH2 or a urea or urethane derivative thereof, in the absence or presence of an inert non-hydroxylic-organic solvent, suitably at above 100 DEG C. and preferably at between 130 DEG C. and 180 DEG C.; (e) by reacting a phthalic halide or ester of the formula <FORM:1012235/C2/5> where R represents a halogen atom or an alkoxy group, with a primary amine of the formula R2NH2; (f) by heating an N-acetylphthalimide of the formula <FORM:1012235/C2/6> with a primary amine R2NH2; (g) by reacting a diazonium salt of an aminophthalimide of the formula <FORM:1012235/C2/7> with a cuprous halide, or with an alkali metal flouroborate and heating the diazonium borofluoride thus obtained, and (h) (where R1 represents chlorine) by chlorination of a phthalimide of the formula <FORM:1012235/C2/8> by methods known per se for the monochlorination of phthalimide compounds, with the proviso that R2 does not represent an alkenyl or alkynyl group, and with the proviso that in processes (b), (d), (e) and (f) R2 does not represent a sulphoxyalkyl or acyloxy alkyl group in which the acyl moiety is derived from a polybasic-carboxylic acid. The compounds may also be prepared by converting one R2 substituent into another by methods known per se. 3 - Amino - N - cyclohexylphthalamide can be prepared heating 3-nitrophthalic anhydride with cyclohexylamine to give 3-nitro-N-cyclo-hexylphthalimide which is reduced with hydrogen in the presence of Raney nickel. Therapeutic compositions with anti-hypertensive properties, e.g. in the form of tablets, pills, powders, granules, emulsions, suspensions, solutions and capsules for oral administration, comprise one or more compounds of the general Formula (I) together with a suitable pharmaceutical carrier.