HIGHLY EFFICIENT SYNTHESIS OF 2,4-DISUBSTITUTED OXAZOLES THROUGH PALLADIUM/COPPER COMEDIATED DIRECT ARYLATION REACTION

  • Venkata Reddy Regalla Department of Chemistry, Koneru Lakshmaiah University, Vaddeswaram, Guntur, Andhra Pradesh, India.
  • Rama Krishnam Raju Addada Department of Chemistry, Koneru Lakshmaiah University, Vaddeswaram, Guntur, Andhra Pradesh, India.
  • Venkat Swamy Puli Department of Chemistry, Koneru Lakshmaiah University, Vaddeswaram, Guntur, Andhra Pradesh, India.
  • Abhishek S Saxena GVK Biosciences Private Limited, Medicinal Chemistry Division, 28A, IDA, Nacharam, Hyderabad, Telangana, India.
  • Anindita Chatterjee Department of Chemistry, Koneru Lakshmaiah University, Vaddeswaram, Guntur, Andhra Pradesh, India.

Abstract

Objective: The aim of the present study is to synthesize 2,4-disubstituted oxazoles through palladium/copper comediated direct arylation reaction.

Methods: 2,4-disubstituted oxazoles (3a-i) have been synthesized by the reaction of 4-substituted oxazole with aryl bromide in the presence of KOH , CuI and Pd(PPh3)4 in dimethoxyethane. Titled compounds (3a-i) were obtained in good yields using an expedient two-step synthesis of 2,4-disubstituted oxazoles from commercially available starting materials

Results: The structures of the newly synthesized compounds were characterized by Fourier-transform infrared, 1H NMR, 13C NMR, and mass spectral studies. This method can be an efficient method for the synthesis of 2,4-disubstituted oxazoles (3a-i).

Conclusion: Pd(PPh3)4 and CuI cocatalytic system direct arylation of 4-aryl/alkyl oxazoles with various aryl bromides has been developed to generate 2,4-disubstituted oxazoles. The high functional group tolerance and the speed of the reaction afford this method appropriate for the combinatorial synthesis of a variety of 2,4-disubstituted oxazoles.

Keywords: Oxazoles, Arylation, Palladium/copper.

References

1. (a) Wipf P. Synthetic studies of biologically active marine cyclopeptides. Chem Rev 1995;95:2115-34. (b) Jin Z. Muscarine, imidazole, oxazole, and thiazole alkaloids. Nat Prod Rep 2003;20:584-605.
2. (a) McGovern SL, Caselli E, Grigorieff N, Shoichet BK. A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening. J Med Chem 2002;45:1712-22. (b) Murcia- Soler M, Perez-Gimenez F, Garcia-March FJ, Salabert-Salvador MT, Diaz-Villanueva W, Castro-Bleda MJ, et al. Drugs and nondrugs: An effective discrimination with topological methods and artificial neural networks. J Chem Inf Comput Sci 2004;44:1031-41.
3. Sarkate AP, Shinde DP. Synthesis and docking studies of 2-(nitrooxy)-ethyl-2-(substituted-2,5-diphenyl-oxazole)-acetate as anti-inflammatory agents with analgesic and nitric oxide releasing properties. Int J Pharm Pharm Sci 2015;7:128-34.
4. Parlapalli A, Cidda KM, Manda S. Antiinflammatory and antioxidant activities of 2-amino-n-(substitutedalkyl)benzoxazole-5-carboxamide derivatives. Int J Pharm Pharm Sci 2014;6:311-4.
5. (a) Lewis JC, Bergman RG, Ellman JA. Direct functionalization of nitrogen heterocycles via Rh-catalyzed C-H bond activation. Acc Chem Res 2008;41:1013-25. (b) Ritleng V, Sirlin C, Pfeffer M. Ru-, Rh-, and Pd-catalyzed C-C bond formation involving C-H activation and addition on unsaturated substrates: Reactions and mechanistic aspects. Chem Rev 2002;102:1731-70. (c) Zhao BG, Han ZB, Ding KL. Organometallic catalysis. Angew Chem Int Ed 2013;52:4744-88. (d) Sakakura A, Ishihara K. Rational design of highly effective asymmetric Diels- Alder catalysts bearing 4,4’-sulfonamidomethyl groups. Chem Soc Rev 2011;40:163-72. (e) Pati K, Liu RS. Gold-catalyzed synthesis of substituted 2-aminofurans via formal [4+1]-cycloadditions on 3-en-1-ynamides. Chem Commun 2012;48:6049 51. (f) Tietze LF, Ila H, Bell HP. Enantioselective palladium-catalyzed transformations. Chem Rev 2004;104:3453-516.
6. (a) Do HQ, Daugulis OJ. Copper-catalyzed arylation of heterocycle C− H bonds. Am Chem Soc 2007;129:12404. (b) Turner GL, Morris JA, Greaney MF. Direct arylation of thiazoles on water. Angew Chem Int Ed 2007;46:7996. (c) Sanchez RS, Zhuravlev A. Mechanistic evidence for a ring-opening pathway in the Pd-catalyzed direct arylation of benzoxazoles. J Am Chem Soc 2007;129:5824.
7. (a) Turchi IJ, Dewar MJ. ???. Chem Rev 1975;75:389-437. (b) Turchi IJ. ???. Ind Eng Chem Prod Res Dev 1981;20:32-76.
8. (a) Shi B, Blake AJ, Lewis W, Campbell IB, Judkins BD, Moody CJ. Rhodium carbene routes to oxazoles and thiazoles. Catalyst Effects in the synthesis of oxazole and thiazole carboxylates, phosphonates, and sulfones. J Org Chem 2010;75:152-61. (b) Xie J, Jiang H, Cheng Y, Zhu C. Metal-free, organocatalytic cascade formation of C–N and C–O bonds through dual sp3 C–H activation: Oxidative synthesis of oxazole derivatives. Chem Commun 2012;48:979-81. (c) Xue WJ, Li Q, Zhu YP, Wang JG, Wu AX.Convergent integration of two self-labor domino sequences: a novel method for the synthesis of oxazole derivatives from methyl ketones and benzoins. Chem Commun 2012;48:3485-7.
9. Hoarau C, Du Fou de Kerdaniel A, Bracq N, Grandclaudon P, Couture A, Marsais F. Regioselective palladium-catalyzed phenylation of ethyl 4-oxazolecarboxylate. Tetrahedron Lett 2005;46:8573.
10. Li X, Murray WV, Macielag MJ, Guan Q. U.S. Patent 113522 A1; 2005.
11. Li J, Chen J, Gui C, Zhang L, Qin Y, Xu Q, et al. Design, synthesis and antitumor evaluation of a new series of N-substituted-thiourea derivatives. Bio Org Med Chem 2006;14:2209-24.
12. (a) Chen R, Liu S, Liu X, Yang L, Deng G. Palladium-catalyzed desulfitative C-H arylation of azoles with sodium sulfinates. Org Biomol Chem 2011;9:7675. (b) Wu M, Luo J, Xiao F, Zhang S, Deng GJ, Luo HA . Palladium-catalyzed direct and Site-selective desulfitative arylation of indoles with sodium sulfinates. Adv Synth Catal 2012;354:335. (c) Wang M, Li D, Zhou W, Wang L. A highly efficient palladium-catalyzed desulfitative arylation of azoles with sodium arylsulfinates. Tetrahedron 2012;68:1926. (d) Zhang M, Zhang S, Liu M, Cheng J . Palladium-catalyzed desulfitative C-arylation of a benzo[d]oxazole C–H bond with arene sulfonyl chlorides. Chem Commun 2011;47:11522.
13. Hachiya H, Hirano K, Satoh T, Miura M. Oxidative nickel–air catalysis in C-H Arylation: Direct cross-coupling of azoles with arylboronic acids using air as sole oxidant. Chem Cat Chem 2010;2:1403-6.
14. Alagille D, Baldwin RM, Tamagnan GD. One-step synthesis of 2-arylbenzothiazole (‘BTA’) and -benzoxazole precursors for in vivo imaging of β-amyloid plaques. Tetrahedron Lett 2005;46:1349-51.
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Regalla, V. R., R. K. R. Addada, V. S. Puli, A. S. Saxena, and A. Chatterjee. “HIGHLY EFFICIENT SYNTHESIS OF 2,4-DISUBSTITUTED OXAZOLES THROUGH PALLADIUM/COPPER COMEDIATED DIRECT ARYLATION REACTION”. Asian Journal of Pharmaceutical and Clinical Research, Vol. 11, no. 8, Aug. 2018, pp. 511-4, doi:10.22159/ajpcr.2018.v11i8.26125.
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