MAGNETIC RESONANCE IN CHEMISTRY Magn. Reson. Chem. 2005; 43: 551–556 Published online 28 April 2005 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/mrc.1588 NMR investigation of hydrogen bonding and 1,3-tautomerism in 2-(2-hydroxy-5-substituted-aryl) benzimidazoles V. Sridharan, S. Saravanan, S. Muthusubramanian * and S. Sivasubramanian Department of Organic Chemistry, Madurai Kamaraj University, Madurai 625 021, India Received 6 December 2004; Revised 15 February 2005; Accepted 28 February 2005 The 1,3-tautomerism associated with 2-(2-hydroxy-5-substituted-aryl)benzimidazoles was studied in different solvents. The effect of hydrogen bonding involving the hydroxyl group of the 2-aryl ring on the tautomerism was investigated using NMR spectroscopy. The influence of the solvent concentration on 2-(2-hydroxy-5-chloroaryl)benzimidazole was studied in acetone-d 6 and DMSO-d 6 . Copyright  2005 John Wiley & Sons, Ltd. KEYWORDS: NMR; 1 H NMR; 13 C NMR; 2D techniques; dynamic NMR; 5-substituted 2-(2-hydroxyaryl)benzimidazoles INTRODUCTION The chemistry 1–4 of suitably substituted benzimidazoles is very important as some benzimidazole derivatives pos- sess anticancer, 5 antiparasitic, 6 antitumour, 7 analgesic 8 and antipoliovirus 9 activities. The 1,3-tautomerism associated with benzimidazoles is a very popular topic and the existence of this tautomerism has been proved by several approaches, including NMR spectroscopy. 10 This 1,3-migration is not found when the imidazole hydrogen is replaced by other substituents such as an alkyl group 11 or under special cir- cumstances where the hydrogen migration is affected by inter- and/or intramolecular hydrogen bonding. We have recently synthesized a set of 2-(2-hydroxy-5- substituted-aryl)benzoxazoles 12 and showed the presence of hydrogen bonding in the compounds between the hydroxy hydrogen and oxazole nitrogen of the benzoxazole ring. It would be interesting to find out in analogous benzimidazoles whether (i) the hydroxyl hydrogen of the 2-aryl group is involved in hydrogen bonding with the imino nitrogen or (ii) the hydroxyl oxygen is involved in hydrogen bonding with the NH of benzimidazole or (iii) there is no hydrogen bonding, in which case the system will have a free tautomeric existence involving 1,3-hydrogen migration. To the best of our knowledge, no systematic study in this respect has been carried out on the related compounds. Hence we planned to prepare a set of 2-(2-hydroxy-5-substituted- aryl)benzimidazoles (2), most of which are new, and to investigate the NMR spectra in solution to address the above hypotheses. L Correspondence to: S. Muthusubramanian, Department of Organic Chemistry, Madurai Kamaraj University, Madurai 625 021, India. E-mail: muthumanian2001@yahoo.com Contract/grant sponsor: DST. RESULTS AND DISCUSSION The target compounds 2 were synthesized by the lead tetraac- etate oxidation of the imines prepared from 2-hydroxy- 5-substituted-benzaldehydes (1) with o-phenylenediamine (Scheme 1). It has been shown that the simple benzalde- hyde on reaction with o-phenylenediamine in a 1 : 1 molar ratio gives the monoimine, which was then subjected to lead tetraacetate oxidation to give benzimidazole. 13 However, in the case of 2-hydroxy-5-substituted-benzaldehydes, even in a 1 : 1 molar ratio of o-phenylenediamine and aldehydes, the diimine 3 and not the monoimine 4 was obtained in moderate yield. The treatment of o-phenylenediamine and the aldehyde in a 1 : 2 ratio, of course, leads to the diimine 3 in very good yield. Upon treatment of the diimine with lead tetraacetate in acetic acid, surprisingly the target benzimidazole 2 was obtained in good yield. Probably the initial hydrolysis of the diimine 3 to monoimine 4 with acetic acid would have occurred, the latter subsequently being oxidized to the target compound 2. The imine 3 has not been separated in many cases and the reaction product of 1 : 1 o-phenylenediamine and aldehyde has been treated with LTA–AcOH to obtain Scheme 1 Copyright  2005 John Wiley & Sons, Ltd.