GB703273A - Manufacture of new derivatives of imidazole - Google Patents

Abstract

The invention comprises benzimidazole compounds, and their salts, containing in the 1-position an unsubstituted or substituted aryl or aralkyl residue and in the 2-position a saturated aliphatic residue which contains at least one basic nitrogen atom (but excluding the compounds of the parent Specification), and the preparation thereof by the following methods: (i) reacting an ester (e.g. a halide or p-toluenesulphonic ester) of an o-nitrophenol with an aminoaryl or aminoaralkyl compound, reducing the nitro group to an amino group and ring-closing the monosubstituted o-diamine by reaction with a compound containing a reactive substituent suitable for ring closure (e.g. a carboxyl, acid chloride, anhydride, ester, amide, amidine or aldehyde group) and also containing (a) a basic group or (b) a substituent (e.g. a halogen atom or an imido-ether group) which is subsequently replaced by a basic group by reaction with ammonia or a primary or secondary amine or diamine; (ii) (a) arylating or aralkylating an o-nitro amine (e.g. by means of the appropriate halide) and reducing the nitro group, or (b) monoarylating or monoaralkylating an o-diamine, and in either case treating the monosubstituted o-diamine as in (i); (iii) ring-closing as in (i) an o-diamine not substituted in either amino group and then arylating or aralkylating the 1-nitrogen atom in the resulting 2-substituted benzimidazole; (iv) acylating a monoarylated or monoaralkylated o-diamine by the action of the halide of a halogenated carboxylic acid under mild conditions, replacing the halogen by a basic residue, and, finally, effecting ring-closure by the application of more energetic conditions; (v) acylating as in (iv) an o-diamine not substituted in either amino group, replacing the halogen by a basic residue, aralkylating the amino group still free by condensation with an aromatic aldehyde followed by catalytic hydrogenation, and, finally, closing the imidazole ring. In examples: (1) 1-benzyl-2-dimethylaminomethylbenzimidazole hydrochloride is prepared by method (i) (b) using chloracetic acid for the ring-closure; the corresponding 2-diethylaminomethyl, 2-n-butylaminomethyl and 2-dimethylaminoethylmethylamino-methyl compounds may be similarly prepared; (2)1-p-chlorobenzyl-2-dimethylaminomethylbenzimidazole hydrochloride is prepared by method (iv) using chloroacetyl chloride for the acylation and effecting ring-closure by boiling in nitrobenzene, or by method (v) or method (i) (b); 1-p-chlorobenzyl-2-diethylaminomethylbenzinimidazole and 1-p-chlorobenzyl - 2 - piperidinomethylbenzimidazole hydrochloride may be similarly prepared; (3) 1-p-methoxyphenyl-2-N-pyrrolidylmethylbenzimidazole is prepared by method (i) (b); (4) in the process of example (4) of the parent Specification, the small crystals of N-o1-methylbenzyl-o-nitraniline are selected for conversion to 1-o-methylbenzyl-2-N-pyrrolidylmethylbenzimidazole hydrochloride.