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Sulphanilic Acid Catalyzed Facile One-pot Synthesis of 2,4,5-Triarylimidazoles From Benzil/Benzoin and Aromatic Aldehydes
Sulphanilic Acid Catalyzed Facile One-pot Synthesis of 2,4,5-Triarylimidazoles From Benzil/Benzoin and Aromatic Aldehydes
Journal of the Korean Chemical Society. 2007. Oct, 51(5): 418-422
Copyright © 2007, The Korean Chemical Society
  • Received : May 28, 2007
  • Published : October 20, 2007
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About the Authors
A. F. Mohammed
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University Aurangabad-431004, (MS), India
N. D. kokare
Wockhardt Research Centre, New Drug Discovery, Aurangabad-431004 (India)
J. N. Sangshetti
D. B. Shinde
Department of Chemical Technology, Dr. Babasaheb Ambedkar Marathwada University Aurangabad-431004, (MS), India

Abstract
A simple and high yielding one-pot method for synthesis of 2,4,5-triarylimidazoles from condensation of benzoin or benzil, ammonium acetate and aromatic aldehydes using sulphanilic acid catalyst is described. The lower priced catalyst, higher yields and shorter reaction time are the advantages of the presented method.
Keywords
INTRODUCTION
Triarylimidazole compounds have gained the remarkable importance due to their widespread biological activities and their use synthetic chemistry. The imidazole ring system is one of the most important substructures found in a large number of natural products and pharmacologically active compounds. For example, the amino acid histidine, the hypnotic agent etomidate, 1 the antiulcerative agent cimetidine, 2 the proton pump inhibitor omeprazole, 3 the fungicide ketoconazole, 4 and the benzodiazepine antagonist flumazenil 5 are imidazole derivatives. In recent years, substituted imidazoles are substantially used in ionic liquids, 6 that has been given a new approach to ‘Green Chemistry’. In addition, they are used in photography as photosensitive compound. 7 Literature survey reveals the several methods for synthesizing them, mainly using nitriles and esters 8 - 10 as the starting substrates. Japp and Radziszewski proposed the first synthesis of theimidazole core in 1882, starting from 1,2-dicarbonyl compounds aldehydes and ammonia, to obtain 2,4,5-triphenylimidazoles. 11 , 12 Subsequently, many other syntheses of this important heterocycle have been published. 13 For example, 2,4-diaryl-1 H -imidazoles are often obtained from amidines and Rbromo arylketones. 14 Moreover, Zhang and Chen described an efficient procedure to obtain unsymmetrical, C5 unsubstituted 2,4-diarylimidazoles. In this approach acetophenones are oxidized in situ to R-tosyloxyacetophenones, which then condense with arylamidines to obtain the desired compounds. 15 Recently, ionic liquids like (Hbim)BF 4 were used for the synthesis of theses compounds in a very short reaction time. 16 Also, the microwave-assisted solid-phase synthetic methods were reported for synthesis of 2,4,5-trylimidazoles using benzil or N -hydroxybenzil, ammonium acetate and aldehydes. 17 , 18 However, some of theses previous methods have suffered from one or more drawbacks like high temperature requirement, highly acidic conditions, and the use of metal cyanides for preparation of the nitrile compounds that limit their uses. 19 - 20 Some of methods have resorted to harsh conditions (e.g. the formamide synthesis, which requires excess reagents, H 2 SO 4 as a condensing agent, 150-200 ℃, 4-6 h, 40-90%). 21 - 23 Therefore, the development of mild, efficient and versatile method is still strongly desirable. Herein, we have presented a novel, mild and efficient method for synthesis of 2,4,5-triarylimidazole using sulphanilic acid catalyst. Out of range of acid catalysts, sulphanilic acid has attracted much attention because of its suitable acidity, eco-friendliness, easy availability and low cost.
RESULTS AND DISCUSSION
Initially, we studied the catalytic efficiency of sulphanilic acid for synthesis of 2,4,5-triphenyl-1 H -imidazole ( 3a ) using benzil, ammonium acetate and benzaldehyde in different solvents and various mol% of sulphanilic acid ( 1 ). The title compound 3a was isolated with 97% yield using optimized reaction conditions ( 1 ), (ethanol-water (1:1) solvent and 10 mol% sulphanilic acid catalyst). Using the standardized reaction conditions, a range of 2-aryl-4,5-diphenyl-1 H -imidazoles were synthesized and results were summarized in 2 . From the results obtained, the aldehydes with electron-donating substituents favor the reaction and it was completed within the shorter reaction time ( 2 , entries 3a, 3h) than the aldehydes with electron-withdrawing substituents ( 2 , entry 3d). Especially, for the p -nitrobenzaldehyde the ( 3d ), the reaction was very slow and also it was the low yielding. The method was found to be effective for hetero-aromatic aldehydes also for the synthesis 2-heteroaryl-4,5-diphenyl-1 H -imidazoles with better yields ( 3i , 3j and 3k ). The easy work-up is advantageous aspect of this method, which includes the pouring of the reaction mixture over ice-water to get the precipitation of solid. It could be filtered to give the sufficiently pure compound in good yield. The present method was superior to the available methods in regards with yields and reaction time. 21 Especially, for the preparation of 2-(4-methylphenyl)-4,5-diphenyl-1 H -imidazole ( 3h ) was synthesized in 96% while the reported yield was 74% and also 2-(2-chlorophenyl)-4,5-diphenyl-1 H -imidazole ( 3b ) was synthesized in 95% while the reported yield was 85 %. 25
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Synthesis of 2,4,5-triarylimidazoles using benzil, aromatic aldehydes, ammonium acetate and 10 mol% sulphanilic acid catalyst.
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Synthesis of 2,4,5-triarylimidazoles using benzoin, aromatic aldehydes, ammonium acetate and 10mol% sulphanilic acid catalyst.
Optimization of reaction conditions and mol% of sulphanilic acid for the synthesis of 1-methylphenyl-2-phenyl-1H-benzimidazoles
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Optimization of reaction conditions and mol% of sulphanilic acid for the synthesis of 1-methylphenyl-2-phenyl-1H-benzimidazoles
Synthesis 2,4,5-triaryl-1H-imidazoles using benzil or benzoin, ammonium acetate, aromatic aldehydes, and 10 mol% sulphanilic acid
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Synthesis 2,4,5-triaryl-1H-imidazoles using benzil or benzoin, ammonium acetate, aromatic aldehydes, and 10 mol% sulphanilic acid
1,2-Diketones (like benzil) are usually prepared from the a-hydroxy ketones (like benzoin) catalyzed by various oxidants. Some of these catalysts are toxic, costly and also required the tedious experimental procedures. 26 To avoid the preparation of starting material 1,2-diketones like benzil, the synthesis of 2,4,5-triphenyl-1 H -imidazole was studied using benzoin. Surprisingly, using the similar reaction conditions, 2,4,5-tripheny-1 H -imidazole was isolated in 93% yield. Encouraged by this result, we extended the methodology for synthesis of various 2,4,5-triaryl-1 H -imidazoles using benzoin and various aromatic aldehydes. The yields obtained were in the range of 66% to 94%.
CONCLUSION
Using 10 mol% sulphanilic acid catalyst, 2,4,5-triaryl-1 H -imidazoles were efficiently synthesized with moderate to excellent yields from benzil and as well as benzoin. For all the presented reactions, the ethanol-water solvent was used which is relatively environmentally benign and supporting to Green Chemistry. The advantages of the reported method are the use of cheap and easily available catalyst, easy work-up, and better yields.
EXPERIMENTAL
1 H NMR spectra were recorded on a 400 MHz Varian-Gemini spectrometer and are reported as parts per million (ppm) downfield from a tetramethylsilane internal standard. The following abbreviations are used; singlet (s), doublet (d), triplet (t), quartet (q), multiplate (m) and broad (br). Mass spectra were taken with Micromass - QUATTROII of WATER mass spectrometer. HPLC was performed using Zorbax SB-C18 reverse phase column (0.46×25 cm) on Shimadzu instrument equipped with an automatic injector with UV-PDA detector. Detection was carried out at 254 nm. The mobile phase consists of 0.05% TFA and acetonitrile (1:1, V/V). The products were eluted at flow rate of 1 ml/min using isocratic method. Flash column chromatog-raphy was performed with 300-400 meshes silica gel and analytical thin layer chromatography was performed on precoated silica gel plates (60F-254) with system (v/v) indicated. Melting points were determined in capillary tubes and are uncorrected.
- General method for the synthesis of 2,4,5-triaryl-1H-imidazoles
A mixture of sulphanilic acid (10 mol%), ammonium acetate (40 mmol), and benzil or benzoin (10 mmol) was dissolved in ethanol-water (20 ml, 1:1, v/v) and to the reaction mixture, aromatic aldehyde (12 mmol) was added. Then, the reaction mixture was heated at 80 ℃ till the reaction was complete (TLC). The reaction mixture was cooled to room temperature and poured on ice-water (50 ml) to get the solid precipitated. It was collected by filtration, washed with water and dried to give the corresponding 2,4,5-triaryl-1 H -imidazoles.
All synthesized compounds were characterized with 1 HNMR and mass. Also the melting points recorded and compared with the corresponding literature mp and found to be matching with those. The representative analytical data for 2,4,5-triphenyl-1H-imidazole (3a) Off-white solid, mp 276-277 ℃ (ref 17 b mp 276-277 ℃), HPLC purity -99.56 %; 1 H NMR (400 MHz, DMSO): δ = 7.55-7.68 (m, 6H), 7.72-7.75 (m, 3H), 7.9-7.95 (m, 6H), 8.8 (bs, 1H); MS (EI, 70 eV): m/z = 296 [M+H] + .
2-(2-chlorophenyl)-4,5-diphenyl-1H-imidazole (3b) Off-white solid, mp 188-189 (ref 16 , mp 188 ℃) ℃; HPLC purity -99.18%; 1 H NMR (400 MHz, CDCl 3 ): δ = 7.5-7.65 (m, 6H), 7.68-7.72 (m, 2H), 7.9-8.0 (m, 6H), 8.7 (bs, 1H); MS (EI, 70 eV): m/z = 330 [M+H] + .
References
Wauquier A. , Van Den Broeck W. A. E. , Verheyen J. L. , Janssen P. A. J. 1978 Eur. J. Pharmacol. 47 367 -    DOI : 10.1016/0014-2999(78)90117-6
Brimblecombe R. W. , Duncan W. A. M. , Durant G. J. , Emmett J. C. , Ganellin C. R. , Parons M. E. 1975 J. Int. Med. Res. 3 86 -
Tanigawara Y. , Aoyama N. , Kita T. , Shirakawa K. , Komada F. , Kasuga M. , Okumura K. 1999 Clin. Pharmacol. Ther. 66 528 -    DOI : 10.1016/S0009-9236(99)70017-2
Heers J. , Backx L. J. J. , Mostmans J. H. , Van Cutsem J. 1979 J. Med. Chem. 22 1003 -    DOI : 10.1021/jm00194a023
Hunkeler W. , Mo¨hler H. , Pieri L. , Polc P. , Bonetti E. P. , Cumin R. , Schaffner R. , Haefely W. 1981 Nature 290 514 -    DOI : 10.1038/290514a0
Wasserscheid P. , Keim W. 2000 Angew Chem. Int. Ed. Eng. 39 37872 -
Satoru I. 1989 Imidazoles derivative for chemiluminescence microanalysis. Japn Kokkai Tokyo Koho JP 01, 117, 867 Chem Abstr 1989, 111, 214482.
Grimmett M. R. 1984 In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Rees, C. W., Eds. Pergamon New York 5 457 -
Grimmett M. R. 1996 In Comprehensive Heterocyclic Chemistry II; Katritzky, A. R., Rees, C. W., Scriven, E. F. V., Eds. Pergamon NewYork 3 77 -
Balalaie S. , Arabanian A. , Hashtroudi M. S. 2000 Monatsh. Chem. 131 945 -    DOI : 10.1007/s007060070049
Radziszewski B. 1882 Chem. Ber. 15 1493 - 1496    DOI : 10.1002/cber.18820150207
Japp F. R. , Robinson H. H. 1882 Chem. Ber. 15 1268 -    DOI : 10.1002/cber.188201501272
Grimmett M. R. 1996 In ComprehensiVe Heterocycle Chemistry II; Katritzky, A. R., Rees, C., Scriven E. F. V., Eds. Pergamon Press Elmsford, NY For example, see, 3 77 - 220
Li B. , Chiu C. K.-F. , Hank R. F. , Murry J. , Roth J. , Tobiassen H. 2002 Org. Proc. Res. DeV. 6 682 -    DOI : 10.1021/op025552b
Zhang P.-F. , Chen Z.-C. 2001 Synthesis 14 2075 -    DOI : 10.1055/s-2001-18059
Siddiqui S. A. , Narkhede U. C. , Palimkar S. S. , Thomas D. , Lahoti R. J. , Srinivasan K. V. 2005 Tetrahedron 61 3539 -    DOI : 10.1016/j.tet.2005.01.116
Wolkenberg S. E. , Wisnoski D. D. , Leister W. H. , Wang Y. , Zhao Z. , Lindsley C. W. 2004 Org. Lett. 6 1453 -
Oskooie H. A. , Alimohammadi Z. , Heravi M. M. 2006 Heteroatom Chemistry 7 699 -    DOI : 10.1002/hc.20237
Davidson D. , Weiss M. , Jelling M. 1937 J. Org. Chem. 2 319 -    DOI : 10.1021/jo01227a004
Zhang E. J. , Moran E. J. , Woiwode T. F. , Short K. M. , Mjalli A. M. 1996 Teterahedron Lett. 37 351 -    DOI : 10.1016/0040-4039(95)02153-1
Usyatinsky A. Y. , Khmelnitsky Y. L. 2000 Tetrahedron Lett. 41 5031 -    DOI : 10.1016/S0040-4039(00)00771-1
Wasserman H. H. , Long Y. O. , Zhang R. , Parr J. 2002 Tetrahedron Lett. 43 3351 -    DOI : 10.1016/S0040-4039(02)00548-8
Deprez P. , Guillaume J. , Becker R. , Corbier A. , Didierlaurent S. , Fortin M. , Frechet D. , Hamon G. , Heckmann B. , Heitsch H. , Kleemann H.-W. , Vevert J.-P. , Vincent J.-C. , Wagner A. , Zhang J. 1995 J. Med. Chem. 38 2357 -    DOI : 10.1021/jm00013a013
Balalaie S. , Hashtroudi A. M. 2000 Monat. Chem. 131 945 -    DOI : 10.1007/s007060070049
Jian-Feng Z. , Yuan-Zhi S. , Yan-Ling Y. , Shu-Jiang T. 2005 Synthetic Communications 35 1369 -    DOI : 10.1081/SCC-200057281
Weiss m , Abbel M. 1948 J. Am. Chem. Soc. 70 3666 -