GB1089853A - Substituted benzimidazoles and compositions containing them - Google Patents

Abstract

Compounds of the formula <FORM:1089853/C2/1> wherein R1 is an acyl radical and each of R2 and R3 is a hydrogen atom or a C1- 6 alkyl or C1- 6 alkoxy group, at least one of R2 and R3 being hydrogen and salts thereof and preparation thereof by reacting a compound of the formula <FORM:1089853/C2/2> wherein R2 and R3 have the above significance and Y is -NH2 with 2-naphthaldehyde and treating the resulting compound of the first general formula above wherein R1 is hydrogen with sodium hydride followed by the appropriate acyl halide. In addition there is disclosed the preparation of substituted benzimidazoles of the first formula above, wherein R1 is hydrogen, alkali metal, C1- 6 alkenyl and R2 and R3 have the above significance by reacting a compound of the second general formula above, wherein Y is -NO2, -NH2 or -NH.R1 (wherein R1 is C1- 6 alkyl or C2- 6 alkenyl) with 2-naphthoic acid or the ester, amide, nitrile or halide thereof in the presence of mineral acid (e.g. polyphosphoric or aqueous sulphuric acid) which cyclises the intermediate anilide or with 2-naphthaldehyde in the presence of an oxidizing agent (e.g. nitrobenzene, cupric acetate, lead tetraacetate, mercuric acetate or air) which converts the intermediate Schiff base to the desired product. In cases where Y is -NO2 the intermediate anilide is reductively cyclised, preferably with a metal/acid system (e.g. Zn/HCl, Zn/HOAc, Fe/HX or Sn/HX). The N-substituted benzimidazoles are obtained by treating compounds of the first formula above wherein R1 is hydrogen with sodium hydride and reacting the resulting alkali metal salt with alkyl, alkenyl or acyl halides. The preparation of 1-methyl-, 1-allyl-, 1-acetyl-, 1-benzoyl-, 5(6)-methyl- and 5(6)-methoxy-substituted 2 - (21 - naphthyl) - benzimidazoles is described.ALSO:Pharmaceutical compositions suitable for oral administration in the veterinary treatment and prophylaxis of helminthiasis, particularly infestations with blood-sucking nematodes such as whipworms and hook-worms, comprise a compound of the formula: <FORM:1089853/A5-A6/1> wherein R1 is hydrogen or alkali metal atom or a C1-6 alkyl, C2-6 alkenyl or acyl radical and each of R2 and R3 being hydrogen, or a C1-6 alkyl or C1-6 alkoxy group, at least one of R2 and R3 being hydrogen, or an acid addition salt thereof, intimately dispersed in or admixed with specified vehicles such as a non-toxic liquid carrier or diluent containing a suspending or dispersing agent or a non-toxic solid carrier or diluent. The compositions may be in unit dosage forms such as a capsule, tablet, bolus or drench containing 5-70% by weight of the active compound or in the form of an animal feed supplement containing 5-50% by weight of the active compound. Compounds of the above formula wherein R1 is acyl may also be used in drinking water.