Use of Solid-Supported Reagents towards Synthesis of 2-Arylbenzoxazole, 3, 5-Diarylisoxazole and 1, 3, 5-Triarylpyrazole


Herein we report a convenient and efficient synthesis of 2-Arylbenzoxazole from the Schiff’s bases of 2-Aminophenol, 3, 5-Diarylisoxazole from α, β-unsaturated ketoxime and 1,3,5-Triarylpyrazole from 2-pyrazoline and N-Arylhydrazone by using milder, less toxic and less expensive-NBS-SiO2, KMnO4-Al2O3, PCC-SiO2 and ACC-Al2O3 as solid-supported oxidizing agents at room temperature. Within the framework of Green Chemistry, the use of solid supported reagents has many advantages such as 1) they are easy to remove from reactions by filtration 2) excess reagents can be used to drive the reaction without introducing any difficulties in purification 3) such solid-supported reagents react differently, mostly more selectively, than their unbound counterparts and 4) toxic, noxious and explosive chemicals are handled more safely when contained on solid support.

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S. Naik and V. Desai, "Use of Solid-Supported Reagents towards Synthesis of 2-Arylbenzoxazole, 3, 5-Diarylisoxazole and 1, 3, 5-Triarylpyrazole," Green and Sustainable Chemistry, Vol. 3 No. 1, 2013, pp. 1-7. doi: 10.4236/gsc.2013.31001.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] R. J. Perry, B. D. Wilson and R. J. Miller, “Synthesis of 2-Arylbenzoxazoles via the Palladium Catalysed Carbonylation and Condensation of Aromatic Halides and O-Aminophenols,” Journal of Organic Chemistry, Vol. 57, No. 10, 1992, pp. 2883-2887. doi:10.1021/jo00036a025
[2] T. Kondo, S. Yang, K.-T. Huh, M. Kobayashi, S. Kotachi and Y. Watanabe, “Ruthenium Complex-Catalysed Facile Synthesis of 2-Substituted Benzoxazoles,” Chemistry Letters, Vol. 20, No. 7, 1991, pp. 1275-1278. doi:10.1246/cl.1991.1275
[3] M. I. E. Sheikh, A. J. Marks and E. R. Biehl, “Investigation of the Synthesis of Benzoxazoles via Aryne Reaction,” Journal of Organic Chemistry, Vol. 46, No. 16, 1981, pp. 3256-3259. doi:10.1021/jo00329a022
[4] T. L. Gilchrist, “Heterocyclic Chemistry,” 3rd Edition, Addison-Wesley Longman, Ltd., London, 1998.
[5] D. Azarifar and M. Shaebanzadeh, “Synthesis and Characterisation of New 3,5-Dinaphthyl Substituted 2-Pyrazolines and Study of Their Anti-Microbial Properties,” Molecules, Vol. 7, No. 12, 2002, pp. 885-895. doi:10.3390/71200885
[6] A. Barco, S. Benitti, G. P. Pollini and D. Simoni, “Synthesis of Natural Products via Isoxazoles,” Synthesis, Vol. 1987, No. 10, 1987, pp. 857-869.
[7] Y. Kondo, D. Uchiyama, T. Sakamoto and H. Yamanaka, “Synthesis and Reactions of 5-(Tributylstannyl)Isoxazoles,” Tetrahedron Letters, Vol. 30, No. 32, 1989, pp. 4249-4250. doi:10.1016/S0040-4039(01)80702-4
[8] O. Morriyo, H. Nakamura, T. Kageyama and Y. Urata, “Synthesis of Isoxazolines and Isoxazoles from Aldoximes by the Use of Sodium Bromite with Organotin Halide,” Tetrahedron Letters, Vol. 30, No. 30, 1989, pp. 3987-3990. doi:10.1016/S0040-4039(00)99302-X
[9] O. Temiz, I. Rren, E. Sener, I. Yalcin and N. Ucartuk, “Synthesis and Microbiological Activity of Some Novel 5-and 6-Methyl-2-(2,4-Disubstitutedphenyl) Benzoxazole Derivatives,” Farmaco, Vol. 53, No. 5, 1998, pp. 337-341. doi:10.1016/S0014-827X(98)00030-5
[10] S. Aiello, G. Wells, E. L. Stone, H. Kadri, R. Bazzi, D. R. Bell, M. F. G. Stevens, C. S. Mathews, T. D. Bradshaw and A. D. Westwell, “Synthesis and Biological Properties of Benzothiazoles, Benzoxazoles and Chromene-4-One Analogues of the Potent Antitumor Agent 2-(3,4-Dimethoxyphenyl)-5-fluorobenzothiazole(PMX610, NSC 721648),” Journal of Medicinal Chemistry, Vol. 51, No. 16, 2008, pp. 5135-5139. doi:10.1021/jm800418z
[11] E. Dominguez, E. Ibeus, E. M. de Margart, J. K. Palacius and E. San Marka, “A Convenient One-Pot Preparative Method for 4,5-Diaryl Isoxazoles involving Amine Exchange Reaction,” Journal of Organic Chemistry, Vol. 61, No. 16, 1996, pp. 5435-5439. doi:10.1021/jo960024h
[12] J. W. Wang, J. Jai, H. M. Li and C. Wang, “Synthesis of Novel Isoxazole-Contained Analogues of Losartan,” Chinese Chemical Letters, Vol. 11, No. 11, 2000, pp. 961-962.
[13] H. Katayama, T. Oshiyama, “Preparation and Bioactivity of Pyrazole Derivatives as Potential Cross-Linking Agents,” Canadian Journal of Chemistry, Vol. 75, No. 6, 1997, pp. 913-919. doi:10.1139/v97-109
[14] H. M. Faid and H. M. Mokhtar, “Pyrazole Derivatives with Possible Hypoglycemic Activity,” Indian Journal of Chemistry, Vol. 27B, No. 3, 1988, pp. 245-249.
[15] R. S. Varma, R. K. Saini and O. Prakash, “Hypervalent Iodine Oxidation of Phenolic Schiff’s Bases: Synthesis of 2-Arylbenzoxazoles,” Tetrahedron Letters, Vol. 38, No. 15, 1997, pp. 2621-2622. doi:10.1016/S0040-4039(97)00444-9
[16] R. S. Varma and D. Kumar, “Manganese Triacetate Oxidation of Phenolic Schiff Bases: Synthesis of 2-Arylbenzoxazoles,” Journal of Heterocyclic Chemistry, Vol. 35, No. 6, 1998, pp. 1539-1540. doi:10.1002/jhet.5570350656
[17] R. G. Shrivastava and P. S. Venkataramani, “Barium Manganate Oxidation in Organic Synthesis: Part III: Oxidation of Schiff’s Bases to Benzimidazoles, Benzoxazoles and Benzthiazoles,” Synthetic Communications, Vol. 18, No. 13, 1988, pp. 1537-1544. doi:10.1080/00397918808081311
[18] K. Nakagawa and H. Onoue, “Oxidation with Nickel Peroxide. IV. The Preparation of Benzoxazoles from Schiff’s Bases,” Chemical and Pharmaceutical Bulletin, Vol. 12, No. 10, 1964, pp. 1135-1138. doi:10.1248/cpb.12.1135
[19] F. F. Stephens and J. D. Bower, “The Preparation of Benzimidazoles and Benzoxazoles from Schiff’s Bases. Part I,” Journal of Chemical Society, Vol. 71, No. 9, 1949, pp. 2971-2972. doi:10.1039/jr9490002971
[20] J. Chang, K. Zhao and S. Pan, “Synthesis of 2-Arylbenzoxazoles via DDQ Promoted Oxidative Cyclization of Phenolic Schiff’s Bases—A Solution Phase Strategy for Library Synthesis,” Tetrahedron Letters, Vol. 43, No. 6, 2002, pp. 951-954. doi:10.1016/S0040-4039(01)02302-4
[21] V.G. Desai and S.G. Tilve, “A Novel and Convenient Method for the Synthesis of 3, 5-Diarylisoxazoles,” Synthetic Communications, Vol. 29, No. 17, 1999, pp. 3017- 3020. doi:10.1080/00397919908086477
[22] R. F. Kurangi, R. Kawthankar and V. G. Desai, “Convenient Synthesis of 3,5-Disubstituted Isoxazoles,” Synthetic Communications, Vol. 37, No. 4, 2007, pp. 585-587. doi:10.1080/00397910601055107
[23] G. Buchi and J. C. Vedera, “Interchange of Functionality Compounds through Isoxazoles,” Journal of American Chemical Society, Vol. 94, No. 26, 1972, pp. 9128-9131. doi:10.1021/ja00781a023
[24] S. P. Singh, D. Kumar, O. Prakash and R. P. Kapoor, “Hypervalent Iodine Oxidation of 1,3,5-Trisubstituted Pyrazolines: A Facile Synthesis of 1,3,5-Trisubstituted Pyrazoles,” Synthetic Communications, Vol. 27, No. 15, 1997, pp. 2683-2689. doi:10.1080/00397919708004136
[25] I. Bhatnagar and M. V. George, “Oxidation with Metal Oxides-II: Oxidation of Chalcone Phenylhydrazones, Pyrazolines, O-Aminobenzylidine Anils and O-Hydroxybenzylidine Anils with Manganese Dioxide,” Tetrahedron, Vol. 24, No. 3, 1968, pp. 1293-1298. doi:10.1016/0040-4020(68)88080-9
[26] W. A. F. Gladstone and R. O. C. Norman, “Reactions of Lead Tetra-Acetate Part VII: Some Reactions Leading to Pyrazoles,” Journal of Chemical Society(C), 1966, pp. 1536-1540. doi:10.1039/j39660001536
[27] G. Sabitha, G. S.K. Kumar Reddy, Ch. S. Reddy, N. Fatima and J. S. Yadav, “Zr(NO3)4: A Versatile Oxidizing Agent for Aromatization of Hantzsch 1,4-Dihydropyridines and 1,3,5-Trisubstituted Pyrazolines,” Synthesis, No. 8, 2003, pp. 1267-1271.
[28] C. Wei-hua and Yi. Pang, “Efficient Synthesis of 2-(2’- Hydroxyphenyl)Benzoxazole by Palladium(II)-Catalyzed Oxidative Cyclization,” Tetrahedron Letters, Vol. 50, No. 48, 2009, pp. 6680-6683. doi:10.1016/j.tetlet.2009.09.084
[29] K. H. Park, K. Jun, S. R. Shin and S. W. Oh, “2-Aryl Benzoxazoles from Phenolic Schiffs Bases by Thianthrene Cation Radical,” Tetrahedron Letters, Vol. 37, No. 49, 1996, pp. 8869-8870. doi:10.1016/S0040-4039(96)02070-9
[30] M. Kidwai, S. Kukreja and R. Thakur, “K2CO3-Mediated Regioselective Synthesis of Isoxazoles and Pyrazolines,” Letters of Organic Chemistry, Vol. 3, No. 2, 2006, pp. 135-139. doi:10.2174/157017806775224170
[31] S. Tang, J. He, Y. Sun and X. She, “Efficient and Regioselective One Pot Synthesis of 3-Substituted and 3,5-Disubstituted Isoxazoles,” Organic Letters, Vol. 11, No. 17, 2009, pp. 3982-3985. doi:10.1021/ol901626n
[32] S. Morrocohi, A. Ricca and A. Zanarotti, “New Features of the Reaction between Nitrilimines and Arylacetylenes,” Tetrahedron Letters, Vol. 11, No. 37, 1970, pp. 3215-3218. doi:10.1016/S0040-4039(01)98434-5
[33] D. Azarifar, M. A. Zulfigol and B. Maleki, “Silica-Supported 1,3-Dibromo-5,5-Dimethylhydantoin (DBH) as a Useful Reagent for Microwave-Assisted Aromatization of 1,3,5-Trisubstituted Pyrazolines under Solvent-Free Conditions,” Synthesis, No. 11, 2004, pp. 1744-1746. doi:10.1055/s-2004-829149
[34] S. Tariq and S. Wakode, “Synthesis through Microwave Irradiation, Characterisation and Evaluation of Antimicrobial Activity of 2-Phenyl-1,3-Benzoxazole Derivatives,” International Research Journal of Chemistry, Vol. 3, No. 9, 2012, pp. 213-217.
[35] C. Praveen, A. Nandakumar, P. Dheenkumar, D. Murlidharan and P. T. Perumal, “Microwave Assisted One Pot Synthesis of Benzothiazole and Benzoxazole Libraries as Analgesics Agents,” Journal of Chemical Society, Vol. 124, No. 3, 2012, pp. 609-624.
[36] B. C. Bishop, K. M. J. Brands, A. D. Gibbs and D. J. Kennedy, “Regioselective Synthesis of 1,3,5-Substituted Pyrazoles from Acetylenic Ketones and Hydrazines,” Synthesi, No. 1, 2004, pp. 43-52. doi:10.1055/s-2003-44376
[37] O. A. Ignatenko, A. N. Blandov and M. A. Kuznetsov, “Oxidative Addition of N-Aminophthalimide to Alkenyl-4,5-Dihydropyrazoles and Alkenyl pyrazoles Synthesis of Aziridinylpyrazoles,” Russian Journal of Organic Chemistry, Vol. 41, No. 12, 2005, pp. 1793-1801. doi:10.1007/s11178-006-0039-3

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