Patent GB-1310998-A (GB)
Title: 4,5,6,7-tetrahydrobenzimidazoles
IPC: D06M13/352
Filed: 1970-09-14
Abstract: 1310998 Tetrahydrobenzimidazoles PLIVA PHARMACEUTICAL & CHEMICAL WORKS 14 Sept 1970 [26 Sept 1969] 43850/70 Heading C2C [Also in Divisions C3 and C5] Novel 4,5,6,7 - tetrahydrobenzimidazoles of the formula in which R 1  represents a hydrogen atom, a straight or branched alkyl group containing 1 to 18 carbon atoms, a hydroxyalkyl or carboxyalkyl group containing 1 to 4 carbon atoms in the alkyl group, a 5 or 6 membered cycloalkyl, alkylcycloalkyl or cycloalkylalkyl group, an arylalkyl group containing 1 to 4 carbon atoms in the alkyl group, a glucosyl, arabinosyl, xylosyl or ribosyl group or other sugar residue derived from hexoses, pentoses or tetroses, or R 1  is the group A-Z, in which A is a straight or branched alkylene group containing 1 to 4 carbon atoms and Z is an amino, lower monoalkylamino, lower dialkylamino, morpholino, N-pyrrolidino, N-piperidino, N-piperazino, N<SP>1</SP>-lower alkyl-N-piperazino, N<SP>1</SP>- (# - hydroxy - lower alkyl) - N - piperazino or N<SP>1</SP> - (# - hydroxy - alkoxy - lower alkyl) - N- piperazino group, R 2  represents a hydrogen atom, a straight or branched alkyl group containing 1 to 20 carbon atoms, a trifluoromethyl, hydroxymethyl or carboxyl group, a carboxyalkyl group containing 1 to 4 carbon atoms, a phenyl-lower alkyl or cyclohexyl-lower alkyl group, a dialkylaminoethylaminocarbonylalkyl, dialkylaminoethylaminocarbonyl or dialkylaminoethoxycarbonylalkyl group containing 1 to 4 carbon atoms in the alkyl group, the 3-(2,3- dihydroxy propionic acid) group, the 3-(2,3- diacetoxy propionic acid methyl ester) group or the 3 - (2,3 - diacetoxy propionic acid dialkylaminoethylamide) group containing 1 to 4 carbon atoms in the alkyl group, the 5-(2,3,4,5- tetrahydroxy valeric acid) group, a polyhydroxyalkyl group containing 4 to 6 carbon atoms, a cyclopentyl or cyclohexyl radical, an alkylcyclohexyl radical containing 1 to 4 carbon atoms in the alkyl group, the carboxyoyclohexyl radical, the 2-, 3- or 4-piperidyl radical, a phenyl, mono or dialkylphenyl radical containing 1 to 4 carbon atoms in the alkyl group, a mono- or dialkoxy phenyl, mono- or dialkoxybenzyl or mono- or dialkoxyphenylethyl radical containing 1 to 4 carbon atoms in the alkoxy group, a 3,4-methylene dioxyphenyl, 3,4-methylene dioxybenzyl or 3,4-methylene dioxyphenylethyl radical, a tetrahydrofuryl group, an acylaminophenyl radical in which the acyl groups are derived from an aliphatic carboxylic acid containing 1 to 3 carbon atoms, the fluorophenyl radical, the 4,5,6,7-tetrahydrobenzimidazolyl - (2) - 1,2 - dihydroxyethyl or 4,5,6,7 - tetrahydrobenzimidazolyl - (2) - 1,2,3,4- tetrahydroxybutyl radical, an imidazolylalkyl, triazolylalkyl or tetrazolylalkyl group containing 1 to 4 carbon atoms in the alkyl group, R 3  represents a hydrogen atom, a straight or branched alkyl group containing 1 to 18 carbon atoms, a carboxyl group or an alkoxycarbonyl radical containing 1 to 4 carbon atoms in the alkoxy group, and R 4  represents a hydrogen atom, or a straight or branched alkyl group containing 1 to 4 carbon atoms, and the acid addition salts and quaternary ammonium salts of the compounds of Formula I above, excepting specifically 4, 5, 6, 7-tetrahydrobenzimidazole and 2-methyl, 5-methyl, 1,2-dimethyl, 2,5- dimethyl, 2-ethyl, 2-ethyl-5-methyl, 2-n-propyl, 2-n-propyl-5-methyl, 2-isopropyl, 2-isobutyl, 2- hexyl, 2-cyolohexyl, 2-phenyl and 2-amisyl- 4,5,6,7-tetrahydrobenzimidazoles, are prepared by hydrogenating a benzimidazole of formula where R 1 , R 2 , R 3  and R 4  are as above, or the unsaturated precursors thereof which can be hydrogenated, (a) in the form of acid addition salts or (b) in the form of free bases and in the presence of at least one equivalent of an acid for each basic group, in the presence of rhodium catalysts, and a polar solvent and, if required, the salt of the 4,5,6,7-tetrahydrobenzimidazole obtained is converted into the free base in known manner and, if required, the free base is converted into an acid addition salt or quaternary ammonium salt by reaction with an inorganic or organic acid or alkylating agent.