Patent ES-363762-A1 (ES)
Title: Benzimidazole Derivatives
Inventor: HOFF D R
IPC: C07D417/04
Filed: 1969-02-17
Abstract: Novel compounds (I) in which X is O or S R 1 is a five-membered monocyclic heteroaromatic ring containing 1-3 O, S or N atoms R 2 is H, OH, C 1-8 alkyl, C 1-8 alkoxy, aralkyl, acyl, acyloxy, carboxyalkoxy, carbamoyl, N-alkylcarbamoyl, or alkoxycarbonyl R 3 is H, or C 1-8 alkyl and R 4 is H, aralkyl, haloaralkyl, cycloalkyl, C 1-8 alkylamino, di - (C 1-8 alkyl)amino, alkylenimino, hetero - interrupted alkylenimino, cycloalkylamino or a radical R-, RO- or RS- in which R is a C 1-8 univalent aliphatic hydrocarbon, C 1-8 univalent aliphatic halohydrocarbon, aryl, haloaryl, alkaryl, aminoaryl or heterocyclic radical and their acid addition salts and metal complexes when R 2 is H are prepared by: (a) reacting an appropriate 5- NH(R 3 )-substituted benzimidazole with R 4 - C(X)Y where Y is a halogen atom (b) reacting an appropriate 5-RS-CO-N(R 3 )- substituted benzimidazole with a compound ROH to give a compound (I) in which X is O and R 4 is RO (R being radical R from ROH) (c) reacting an appropriate 5-isothiocyanato benzimidazole with a compound ROH or RSH to give a compound (I) in which X is S and R 4 is RO- or RS- (d) reacting a compound (I) in which X is O with phosphorus pentasulphide to give a compound (I) in which X is S (e) reacting an appropriate 5-NH(R 3 )- substituted benzimidazole with an alkyl isocyanate or isothiocyanate to give a compound (I) in which R 4 is alkylamino (f) reacting an appropriate 5-NH(R 3 )- substituted benzimidazole with a dialkylcarbamoyl halide to give a compound (I) in which X is O and R 4 is dialkylamino (g) reacting a compound (I) in which X is O and R 4 is alkylthio with a dialkylamine, alkylenimine or hetero-interrupted alkylenimine to give a compound (I) in which R 4 is dialkylamino, alkylenimino or hetero-interrupted alkylenimino (h) reacting an appropriate 5- isothiocyanato-benzimidazole with a dialkylamine, alkylenimine or hetero-interrupted alkylenimine to give a compound (I) in which X is S and R 4 is dialkylamino, alkylenimino or hetero-interrupted alkylenimino or (i) introducing the group R 2 into an appropriate benzimidazole by reacting an alkali metal salt of a compound (I) in which R 2 is H with an alkyl, aralkyl or acyl halide, or by reacting a compound (I) in which R 2 is H with an alkyl isocyanate to give a compound (I) where R 2 is carbamoyl, or by reacting a compound (I) in which R 2 is H with an alkyl haloformate to give a compound (I) in which R 2 is alkoxycarbonyl followed in any of (a)-(i) by salt formation, where desired. Intermediates isolated are 5-nitro-2-(41-thiazolyl)-benzimidazole, prepared by nitration of the 5 - unsubstituted compound 5 - nitro - 2 - (21 - furyl) - benzimidazole, 5 - nitro - 2 - (21- pyrryl) - benzimidazole and 5 - nitro - 2 - (21- thienyl) - benzimidazole, prepared by reacting the appropriate furan-, pyrrole- or thiophene- 2 - aldehyde with o - amino - p - nitro - aniline 5 - amino - 2 - (41 - thiazolyl) - benzimidazole, prepared by reduction of the 5-nitro compound 5 - isothiocyanato - 2 - (41 - thiazolyl) - benzimidazole, prepared from the 5-phenoxythiocarbonylamino compound by heating in pyridino 5 - nitro - 1 - methoxy - 2 - (41 - thiazolyl)- benzimidazole, prepared by nitration of the 5- unsubstituted compound and 5-amino-1-methoxy - 2 - (41- thiazolyl) - benzimidazole hydrochloride, prepared by reduction of the previous intermediate. Pharmaceutical compositions comprise a novel compound (I) in conjunction with a suitable carrier or diluent and are suitable for oral or parenteral administration as anthelmintics or antifungal agents.