Novel one-pot synthesis of (4 or 5)-aryl-2-aryloyl-(1H)-imidazoles in water and tauto-isomerization study using NMR Behzad Khalili, Tahereh Tondro, Mohammed M. Hashemi * Department of Chemistry, Sharif University of Technology, PO Box 11365-9516, Tehran, Iran article info Article history: Received 13 January 2009 Received in revised form 2 June 2009 Accepted 19 June 2009 Available online 25 June 2009 abstract A simple and green route to synthesis of (4 or 5)-aryl-2-aryloyl-(1H)-imidazoles is described. Two iso- mers can tautomerize to each other by the heat absorption. The tauto-isomerization process was studied by NMR technique. Acidity and stability of products were studied using B3LYP method. Ó 2009 Elsevier Ltd. All rights reserved. 1. Introduction As an important member of the five-membered ring heterocycles, the imidazole moiety is present in a wide range of naturally occurring molecules. 1 It is a common scaffold in highly significant biomolecules, including biotin, the essential amino acid histidine, histamine, and the pilocarpine alkaloids. 2 Imidazoles also have an ability to behave as ligands in metalloenzymes and non-natural metal complexes. 3 The use of imidazoles and their derivatives in chemical processes, espe- cially in pharmaceuticals, is becoming increasingly important, be- cause of the possibility of hydrogen bond formation. 4 Compounds with an imidazole moiety have many pharmaceutical activities, sev- eral of which have been incorporated in marketed drugs such as ci- metidine and losartan. 5 The biological importance of the imidazole ring system has made it a common structure in numerous synthetic compounds, such as fungicides, 6 herbicides, 6 plant growth regula- tors 7 and therapeutic agents. 8 Recently, advances in green chemistry and organometallic chemistry have extended the boundary of imid- azoles to the synthesis and application of a large class of imidazoles such as ionic liquid and imidazole 9 related N-heterocyclic carbenes. 10 Due to their wide range of biological, industrial and synthetic appli- cations, these compounds have recently received a great deal of at- tention. There are several methods reported in the literature for the synthesis of imidazoles, such as hetero-cope rearrangement, 11 four component condensation of aryl glyoxals, primary amines, carboxylic acids and isocyanides on Wang resin, 12 reaction of N-(2-oxo)amides with ammonium trifluroacetate, 13 1,2-aminoalcohols in the presence of PCl 5 , 14 diketones, aldehydes, amine and ammonium acetate 15 ; from a-aminonitriles, 16 Palladium-catalysed 17 cyclisation of o-pen- tafluorobenzoylamidoximes, 18 from keto-oxime, aldehydes and am- monium acetate. 19 To the best of our knowledge, there are no reports in the literature on the formation of (4 or 5)-aryl-2-aryloyl-(1H)-imi- dazole derivatives via condensation of arylglyoxals with ammonium acetate. In this paper, we describe the one-pot reaction between arylglyoxals 2 and excess amount of ammonium acetate in water to give (4 or 5)-aryl-2-aryloyl-(1H)-imidazoles (1a or 1b)(Scheme 1). 2. Results and discussion During our latest work describing the synthesis of new pyrole derivatives, 20 we found that in some cases 1,3-dicarbonyl com- pounds did not react and were recovered. Therefore the reactions were repeated without using 1,3-dicarbonyl compounds to give new compounds which were characterized as imidazole de- rivatives. For example, the reaction of 4-methoxyphenylglyoxal in the presence of an excess amount of ammonium acetate in ethanol at room temperature was carried out. 1 H NMR gave two signals for NH with different intensities (13.4 ppm with high intensity and 13.5 ppm with low intensity), two singlet signals for the CH of imidazole ring (7.90 ppm with high intensity and 7.64 ppm with low intensity), two different signals for phenyl groups, and two different signals for both methyl groups (Figs. 1a–c in Supple- mentary data). These results show that there are two isomeric 2-aryloylimidazoles. The signal for NH of 4-aryl-2-aryloyl- (1H)-imidazole (isomer 1a) has a lower chemical shift (ppm) than 5-aryl-2-aryloyl-(1H)-imidazole (isomer 1b). The a/b ratio was determined by 1 H NMR, using the intensities of the NH of the im- idazole rings of two isomers. Two isomers (a and b) can be gen- erated via a [1,5]-hydrogen shift as shown in Scheme 2. According O O Ar H NH 4 OAc N N H Ar O Water, rt 2 1a Ar N N H Ar O Ar 1b + Scheme 1. Synthesis of (4 or 5)-aryl-2-aryloyl-(1H)-imidazole. * Corresponding author. Tel.: þ98 2166165313; fax: þ98 2166165718. E-mail address: mhashemi@sharif.edu (M.M. Hashemi). Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet 0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved. doi:10.1016/j.tet.2009.06.082 Tetrahedron 65 (2009) 6882–6887 Contents lists available at ScienceDirect Tetrahedron journal homepage: www.elsevier.com/locate/tet