%0 Journal Article
%T Synthesis of N-Alkyl-2-thiomethyl Benzimidazoles: A Green Approach
%A S. Srinivas Rao
%A Ch. Venkata Ramana Reddy
%A P. K. Dubey
%J Organic Chemistry International
%D 2014
%I Hindawi Publishing Corporation
%R 10.1155/2014/239710
%X A green approach for the synthesis of N-alkyl-2-thiomethyl benzimidazoles 2 (R=CH3, C2H5, CH2Ph) under different conditions has been developed from N-alkyl-2-chloromethyl benzimidazole (i.e., CH3, C2H5, CH2Ph) 1 by reaction with thiourea by physical grinding, or by using green solvents like ethanol and PEG-600, or by using microwave irradiation technique. 1. Introduction Benzimidazoles are very useful intermediates/subunits for the development of molecules of pharmaceutical or biological interest [1, 2]. Benzimidazoles are an important class of bioactive molecules in the field of drugs and pharmaceuticals [3¨C7]. N-Methyl-o-phenylenediamine on treatment with thioacetic acid in HCl under reflux gave N-methyl-2-thiomethyl benzimidazole that was reported [8] by Casella et al. Rall et al. described [9] that N-methyl o-Phenylenediamine with S-benzyl thioacetic acid in aq. HCl under reflux gave N-benzyl-2-benzylthio methylbenzimidazole. Kato et al. reported [10] that 2-((methylthio)methyl)-1H-benzimidazole was prepared on treatment of S-methylthio acetic acid with o-phenylenediamine in aq. HCl under reflux for 16£¿hr. Reaction of S-methylthio methylbenzimidazole on treatment with methyl iodide in presence of sodium methoxide gave N-methyl-S-methylthio methylbenzimidazole that was reported by Haugwitz et al. [11]. Zubenko et al. reported [12] that N-methyl-2-chloromethyl benzimidazole was reacted with thiomethane in ethanol in NaOMe and gave N-methyl-2-methylthio methylbenzimidazole. Rao et al. [13] reported that N-alkyl-2-chlorobenzimidazole was treated with thiourea green conditions and gave N-alkyl-2-thiomethyl benzimidazole in good yields. In continuation of our earlier studies [14], we now wish to report a green syntheses of N-alkyl-2-thiomethylbenzimidazoles. 2. Results and Discussion Reaction of 1a¨Cc, that is, N-alkyl-2-chloromethyl benzimidazole [8] (R=CH3, C2H5, or PhCH2), independently, each with thiourea by a simple physical grinding of the reaction mixture in a mortar with a pestle, under solvent-free conditions, for 10¨C15£¿min at RT, followed by simple processing, gave respectively (1-methyl-1H-benzimidazol-2-yl)methanethiol (2a, i.e., 2, R=CH3), (1-ethyl-1H-benzimidazol-2-yl)methanethiol (2b, i.e., 2, R=C2H5), and (1-benzyl-1H-benzimidazol-2-yl)methanethiol (2c, i.e., 2, R=CH2Ph) in excellent yields, matching the products identically with the ones reported [8] by the literature in all respects (m.p., m.m.p., and co-TLC) (Scheme 1). Scheme 1: 2a, R=CH 3; 2b, R=C 2H 5; 2c, R=CH 2Ph. The reaction of 1a, 1b, and 1c, independently, each with thiourea in
%U http://www.hindawi.com/journals/oci/2014/239710/