Application of Resin-Bound Reagents for the Synthesis of Benzimidazole Derivatives

Abstract

In an efficient exploitation of solid-phase chemistry, this work describes the preparation of the new resin-bound 4-( N-arylamino)-3-aminobenzoates and their successful cyclocondensations with the sodium bisulfite adducts of different aldehydes and triethyl orthoformate or triethyl orthoacetate, followed by resin cleavage to produce the target 1,2-diaryl- and 1-aryl-2-(un)substituted benzimidazole-5-carboxylic acid derivatives, respectively. In another variation, the cyclocondensation of the resin-bound 4-( N-arylamino)-3-aminobenzoates with carbon disulfide afforded the corresponding resin-bound thioxobenzimidazoles, which upon cleavage gave the corresponding 2-thioxobenzimidazoles. S-Alkylation of the resin-bound thioxobenzimidazoles with benzyl chloride and 4-bromophenacyl bromide furnished 2-benzylsulfanyl benzimidazoles and 4-bromophenyl-2-oxoethylsulfanyl-benzimidazoles, respectively. Reacting the resin-bound 4-( N-arylamino)-3-aminobenzoates with phenyl isothiocyanate gave the open-form 4-(arylamino)-3-(3-phenylthioureido) benzoic acids. Moreover, the reaction of the resin-bound 4-( N-arylamino)-3-aminobenzoates with N,N-carbonyldiimidazole yielded the corresponding 2-bezimidazolones.