Green route for the heterocyclization of 2-mercaptobenzimidazole into b-lactum segment derivatives containing –CONH– bridge with benzimidazole: Screening in vitro antimicrobial activity with various microorganisms Krunal G. Desai * and Kishor R. Desai Department of Chemistry, Faculty of Science, Synthetic Organic Chemistry Research Laboratory, Veer Narmad South Gujarat University, Udhna-Magdalla Road, Surat (west)-395 007, Gujarat State, India Received 31 July 2006; revised 5 September 2006; accepted 8 September 2006 Available online 10 October 2006 Abstract—The efficient and rapid synthesis of novel azetidin-2-ones 4a–j has been established. Thus, both microwave and conven- tional condensation 2-{(1H-benzimidazol)-ylthio}-N 0 -2-(substituted phenyl) hydrazide with chloroacetylchloride were carried out in DMF-benzene solvent in the presence of Et 3 N catalyst. The microwave synthesis route afforded better yield with short time. The novel heterocycles were characterized by elemental analysis and spectral features. Some of the produced compounds were screened for their antimicrobial activity. Ó 2006 Elsevier Ltd. All rights reserved. 1. Introduction 2-Mercaptobenzimidazole derivatives are known to pos- sess varied biological activities. 1 2-Azetidinone deriva- tives have been reported to possess anti-inflammatory, 2 anticonvulsant, 3 fungicidal, 4 antibiotic, 5 anticancer, 6 antielastase, 7 antiviral, 8 antimicrobial, 9 antitumor, 10 anti-HCMV, 11 antibacterial 12 activities and pharmalog- ical interest. 13 The incorporation of a 2-oxoazetidine moiety in to 2-mercaptobenzimidazole scaffold enhances its activity. In the last few years, microwave-induced organic reac- tion enhancement (MORE) has gained popularity as a non-conventional technique for rapid organic synthe- sis 14 and many researchers have described accelerated organic reactions, with a large number of papers that have appeared proving the synthesis utility of MORE chemistry in routine organic synthesis. 15,16 It can be termed as ‘e-chemistry’ because it is easy, effective, eco- nomical, and eco-friendly, and is believed to be a step toward achieving green chemistry objectives. Within the framework of ‘Green Chemistry’ we have now devel- oped an environmentally benign and novel approach for the synthesis of azetidine-2-ones. In view of the above, and in continuation to our earlier work on the applica- tion of MORE 17–19 chemistry to organic synthesis and the biological importance of 2-azetidinones, we now report a simple, novel and environmentally benign ap- proach using facile, microwave synthesis of 2-azetidi- nones 4a–j from precursors 3a–j and ClCH 2 COCl using triethylamine (TEA) as a catalyst (Fig. 1). 0968-0896/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved. doi:10.1016/j.bmc.2006.09.017 Keywords: 2-Azetidinones; Heterocyclization; Microwave effect; Anti- microbial interest. * Corresponding author. Tel.:/fax: +91 0261 2258384; e-mail: kgdapril@yahoo.co.in N H N SCH 2 C O NH N C H Cl O R 1 2 3 4 5 6 1' 2' 3' 4' 1" 2" 3" 4" 5" 6" 7" 4 R 4 R a 4-NO 2 f 2-OCH 3 b 3, 4, 5-(OCH 3 ) 3 g 4-OCH 3 c 2-OH h 2-Cl d 3-OH i 3-Cl e 4-OH j 4-Cl Figure 1. General structure of synthesized 2-azetidinones 4a–j. Bioorganic & Medicinal Chemistry 14 (2006) 8271–8279