Zinc Sulfamate Catalysed Synthesis of Trisubstituted Imidazole
Jairaj K Dawle1*, Suryawanshi V B2, S R Mathapati3, A S Bondge4, K I Momin5
1Reserch Lab of Pure and Applied Chemistry, Maharashtra Mahavidhyalaya, Nilanga, Dist: Latur.
2Department of Chemistry, K M C College, Khopoli, Dist Raigad.
3Department of Chemistry, S. M. P. College, Murum, Omerga, Dist: Osmanabad.
4Department of Chemistry, Shivneri Mahavidhyalaya, Shirur Anantpal, Dist Latur.
5Department of Chemistry, Rajshri Shahu Mahavidhyalaya, Latur.
*Corresponding Author E-mail: amritkund_jk@rediffmail.com
ABSTRACT:
Numerous imidazole derivatives are reported as pharmacological agents like azomycin, clotrimazole, Miconazole, ergothionine, clonidine and moxonidine. One of the most important applications of imidazoles derivatives are treatment for denture and cancer therapy. Imidazoles are in general, well known to possess, anti-cancer activity. These compounds are 5 membered planar ring, soluble in water and other polar solvents. Radziszewski and Jaapproposed the first synthesis of the imidazole corein 1882, starting from 1,2-dicarbonyl compounds, aldehydes and ammonia to obtain 2,4,5-triphenylimidazole [1, 2].
KEYWORDS: Imidazole, Zinc Sulphate, trisubstitution etc.
Lot of synthetic procedures are available for the synthesis of imidazoles, including the reaction between glyoxal and formaldehyde resulted 2-mono substituted and 2,4,5 homo trisubstitutedimidazoles (Debus synthesis). Similarly, N,N’-diethyloxalamide on treatement with phosphorous oxychloride in the presence of phosphorous penta chloride resulted 1,2 disubtitutedchloroimidazoles (Wallach chloroimidazole synthesis). To sylmethylisocyanide on reaction with N-benzylidenebenzenamine gives 1,4,5trisubstitute dimidazoles[3]. In addition triarlyimidazoles are also used in photography as photo sensitive compounds [4]. The classical synthesis of triarylimidazoles involves multi component condensation of 1,2-di ketone, α-hydroxy ketone or ketoxime with and aldehyde and ammonia (or its salt)under pressure [5].
Review of literature has revealed a variety of catalyst used in these reactions, Viz., ionic liquids [6], silica supported sulphuric acid [7] acetic acid [8], NiCl2.6H2O/Al2O3 [9], iodine [10], sodium bi sulphite [11], p-toluene sulfonic acid [12], In Cl3.3H2O [13], ceric ammonium nitrate [14], However, a meager have been observed in amino acid catalyzed reactions [15,16].
However, some of these protocols have not been entirely satisfactory because of such drawbacks as low yields, long reaction time, strong acidic conditions, tedious workup procedures, requirement of excess amounts of catalyst and use of toxic reagents, catalysts or solvent, cumbersome experimental processes, and use of moisture-sensitive and costly catalysts. Ultrasonic and Microwave irradiation methods also reported for this synthesis, but need special instrument.
So, it is necessary to find a new catalyst for this important reaction. To overcome all these disadvantages here we report a practical, inexpensive and green method for the synthesis of imidazole derivatives. We have found that zinc sulfamate can smoothly catalyze the cyclocondensation efficiently with the advantages of rapid reaction rates, high yields, no corrosion of equipment, ease of manipulation, and low-cost catalyst. This prompted us to extend the scope of zinc sulfamate catalysed cyclization for the synthesis of imidazole derivatives.
In this work, we report the synthesis of 2,4,5-trisubstituted imidazoles using zinc sulfamate as a catalyst under classical heating. We examined a wide variety of aromatic or aliphatic aldehydes with various substituents to establish the catalytic importance of zinc sulfamate for this reaction. A wide range of ortho-, meta- and para-substituted aromatic aldehydes undergo this one-pot multicomponent synthesis with Benzoin and ammonium acetate to afford 2,4,5-trisubstitute dimidazoles in good yields.
RESULT AND DISCUSSION:
Literature gives various process for the synthesis of trisubstituted imidazole. In the present work we are synthesis trisubstitted imidazole derivatives from the benzoin. In the first step Benzyl was synthesis from benzoin by reported process. Imidazole derivatives are synthesis from Benzyl, and ammonium acetate in ethanol and Zinc sulfamate as catalyst.
The compounds reported in this project work ie. Derivatives of trisubstitted imidazole. Final compounds were prepared due to its biological activity. These products were good in yield in presence of zinc sulfamate catalyst. The key advantages of this process are high yield, cost effectiveness of catalyst, easy work up etc. The yield and malting point of synthesized compounds are given in Table.
EXPERIMENTAL WORK:
All the chemicals used for synthesis were of LR (Laboratory Reagent) grade. TLC (Thin Layer Chromatography) was performed on microscopic glass slides coated with silica gel-G, using chloroform: ethyl acetate (7:3) as a solvent systems and the spots were visualized by exposure to iodine vapors. The IR spectrum of synthesized compounds was recorded on FT-IR Spectrophotometer using potassium bromide.
Step I : General procedure for the synthesis of Benzyl from Benzoin 1
Benzoin (5.0 g, 0.235 mol) was placed in a 1000 mL Erlenmeyer flask and concentrated nitric acid (250 mL) was added into it in a fumecupboard. The mixture was heated on a hot plate with occasional shaking until all the red colored nitrogen oxide gas was evolved (about 2 hours). The mixture was transferred to another 2000 ml Erlenmeyer flask which contained 1000 ml distilled water and stirred vigorously until the oil solidified as a yellow crystalline material. It was filtered over a Buchner funnel and washed with a liberal quantity of cold water until all the excess HNO3 was removed. The solid material was recrystallized from 95% ethanol which resulted yellow needle crystalline material. Its m.p. was found to be 92°C (literature 95°C).
Its IR (mull in nujol) (cm-1): 3050 (C=CH, aromatic), 1680 (C=O, s), 1595, 1585, 1450 (C=C aromatic, m).
Step II : General procedure for the synthesis of Trisubstituted Imidazole Derivative From Benzyl.
A mixture of various substituted aldehyde4a-h (1 mmol), benzil 2 (1 mmol), ammonium acetate 3(5 mmol) and Zinc sulfamate (3 mmol, 30 mol %) as a catalyst in a 10 ml ethanol was stirred at 110 oC for 45-75min. After completion of the reaction, the reaction was cooled to room temperature and solid materials washed with water and the solvent was evaporated to give the crude product. For further purification it was recrystallized from ethanol 96% to afford pure product.
Spectral and Analytical Data:
2,4,5-Triphenyl-1H-imidazole (5a): MP. 271-272 oC. FTIR (KBr, cm-1): 3434(NH), 2993, 2470, 1638(C=C), 1510(C=N); 1H NMR (300 MHz, DMSO-d6): 12.7 (s, 1H), 8.1 (d, J¼7.8 Hz, 2H), 7.1-7.9 (m, 13H, arom.); 13C NMR (300 MHz, DMSO-d6): d 146, 136, 135.4, 130.8, 130, 129, 128.75, 128.3, 127.5, 127, 125.6.
2-(2-Hydroxyphenyl)-4,5-diphenyl-1H-imidazole: (5c)M.p. 209–211 °C (Ref. 24) 209–210 °C; IR (KBr) max ν% / cm–1: 3450, 3385, 1584, 1529, 1480, 1240, 1098. 1 HNMR (400.13 MHz, CDCl3) δ / ppm: 6.92 (d, J = 7.28 Hz, 1H), 7.08 (d, J = 7.7 Hz, 1H), 7.26–7.62 (m, 12H), 9.36 (s, 1H), 12.83 (s, 1H). 13CNMR (100.62 MHz, CDCl3) δ / ppm: 111.39, 116.80, 117.92, 122.00, 126.32, 127.14, 127.38, 128.07, 129.54, 144.67, 156.45.
-(4-Methoxyphenyl)-4,5-diphenylimidazole (5d):
IR (KBr, cm−1): 3400, 3060, 1611, 1490, 1179, 1028, 830, 761; 1HNMR (DMSO-d6, 300MHz): δ=12.52 (s, 1H), 8.03 (dt, J=8.80 Hz, 2.0 Hz, 2H), 7.70-7.10(m, 10H), 7.03 (dt, J=8.8 Hz, 2.0 Hz, 2H), 3.81 (s, 3H); 13C NMR (300 MHz, DMSO-d6): 158.32, 145.09, 136.01, 134.62, 131.38, 12130, 127.4, 126.01, 123,07, 113.89, 54.62 ppm.
2-(3-Nitrophenyl)-4,5-diphenyl-1H-imidazole (5e):
M.p. 308–309 °C (Ref. 27) >295 °C; IR (KBr) max ν% / cm–1: 3380, 3065, 1580, 1527, 1479, 1239, 1099, 810, 758. 1 HNMR (400.13 MHZ, DMSO-d6) δ / ppm: 7.30– 7.53 (m, 10H), 7.78 (t, J = 8 Hz, 1H), 8.51 (d, J = 8 Hz, 1H), 8.95 (t, J = 1.8 Hz, 1H), 9.41 (d, J = 8 Hz, 1H), 13.10 (s, 1H), 13CNMR (100.62 MHz, DMSO-d6) δ / ppm: 119.40, 122.61, 127.13, 128.44, 128.68, 130.44, 131.17, 131.82, 143.38, 148.37.
2-(4-Nitrophenyl)-4,5-diphenyl-1H-imidazole (5f):
Mp 199–201 oC. (KBr, cm-1): 3421(NH), 2928, 1596(C=N), 1515, 856; 1HNMR (DMSO-d6, 300MHz): 7.00-8.52 (m., 14H, arom.), 11.7(s. br., NH); 13C NMR (300 MHz, DMSO-d6): 124.165, 126.659, 126.862, 128.568, 129.631, 130.341, 131.103, 131.435, 134.737, 137.891, 148.069, 145.633, 147.460 ppm.
Table: Analytic data of synthesized trisubstituted imidazole derivatives 5(a-h)
|
Sr.No |
Structure of products |
Molecular formula |
M.P. in oC |
Yield in % |
|
1 |
|
C21H16N2 |
260 |
90 |
|
2 |
|
C21H15N2Cl |
180 |
85 |
|
3 |
|
C21H16 O N2 |
175 |
82 |
|
4 |
|
C22H18 ON2 |
170 |
80 |
|
5 |
|
C21H15O2N3 |
280 |
90 |
|
6 |
|
C21H15O2N3 |
203 |
85 |
|
7 |
|
C16H14N2 |
220 |
86 |
|
8 |
|
C15H12N2 |
210 |
82 |
CONCLUSION:
It is evident from this work that the trisubstituted imidazoles can be well synthesized as evident from their spectral authentication using zinc sulphate in the catalytic amount as a catalyst.
ACKNOWLEDGEMENT:
The authors are thankful to their respective institution authorities and also to IICT, Hyderabad And NCL , Pune for providing spectral data.
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Received on 01.12.2016 Modified on 24.12.2016
Accepted on 30.12.2016 © AJRC All right reserved
Asian J. Research Chem. 2016; 9(12): 674-678.
DOI: 10.5958/0974-4150.2016.00093.6