Indian Journal of Chemistry Vol. 55B, June 2016, pp. 707-712 A convenient route to benzimidazole fused chiral heterocyclic bases Swapnil J Wagh, Trupti S Tawde, Jai V Sapre, Vaibhav N Khose & Anil V Karnik* Department of Chemistry, University of Mumbai, Vidyanagari, Mumbai 400 098, India E-mail: avkarnik@chem.mu.ac.in Received 6 May 2015; accepted (revised) 8 February 2016 An efficient synthetic protocol has been developed to obtain new chiral heterocyclic bases pyrrolo-benzimidazoles (DHP-Bz) and thiazolo-benzimidazoles (DHT-Bz). Notable characteristic of both series of the fused heterocycles is the presence of a chiral center. Chiral HPLC separations of the fused heterocycles have been achieved. These molecules possess structural features well-suited to function as chiral organocatalysts after resolution, apart from potential biological activities. Keywords: Benzimidazole, organocatalyst, chiral bases, fused heterocycles, multiple hetero-atoms Chiral heterocyclic molecules have been considered as very fascinating and occupy a significant position in heterocyclic chemistry 1 . The nitrogen containing chiral heterocycles have found use as ‘aminocatalysts’ in many types of reactions such as Baylis-Hilmann 2 , Michael addition 3 , aldol condensation 4 , asymmetric Diels-Alder 5 , Mannich reaction 6 , etc. A large number of nitrogen containing heterocycles have been employed in many stereo-discrimination processes 7 . Benzimidazoles, pyrroles and thiazoles are also bestowed with significant biological activities. Cinchona and quinine alkaloids are naturally occurring heterocyclic amines which have found applications as chiral auxiliary, organo-catalysts and resolving agents 8 . Many of these naturally occurring heterocyclic bases, though efficient, are expensive, which limits their use in chiral chemistry. Thus, there is a need to develop chiral heterocyclic bases, accessible through easy synthetic protocols. This has resulted in undiminished research in this exciting area in the last 3 to 4 decades. Presence of two or more tertiary nitrogens is one of the desired structural features for potential organo- catalysts. Proceeding on this hypothesis and in continuation to our quest for novel chiral bases for organocatalysts, we have successfully developed several benzimidazole based systems for some stereodiscrimination processes 9 . With our reasonable success in benzimidazole chemistry, it was decided to use benzimidazole as a starting moiety to develop potent heterocyclic organocatalysts. We focused on the synthesis of two new class of benzimidazole fused chiral heterocycles namely, 3-aryl-2,3-dihydro[1,3]thiazolo[3,2- a] benzimidazoles [DHT-Bz] 3a-c and 1-aryl-2,3- dihydro-1H-pyrrolo[1,2-a] benzimidazoles [(DHP-Bz] 6a-b (Figure 1). Herein, we report efficient synthetic approaches for the preparation of chiral benzimidazole based [DHT-Bz] 3a-c and [(DHP-Bz] 6a-b. Results and Discussion We decided to employ 2-mercaptobenzimidazole as the synthon for development of fused heterocyclic system (DHT-Bz) 3a-c. Compound 1a-b were obtained by alkylation reaction with 4-substituted phenacyl bromide using reported procedure 10 . Based on our experience 11 of formation of secondary carbocation from aryl-alkyl carbinols followed by intramolecular attack of the internal nucleophile to obtain cyclised products, we decided to reduce the compounds 1a-c using NaBH 4 . The reduced products were well characterized. On refluxing 2a-c in 1N HCl the desired fused heterocyclic bases 3a-b were obtained in 70-75% yield 12 (Scheme I). The compounds were fully characterised by spectroscopic techniques. The 1 H NMR of 3a showed three dd’s at δ 3.84, 4.81 and 5.81 respectively for –CH-CH 2 proton linkage with geminal couplings, along with one singlet at δ 3.81 for –OCH 3 protons. The DEPT NMR showed one negative peak at δ 43.89 which confirmed the presence of methylene proton. In addition, HSQC NMR showed one cross peak at δ 4.36 correlating