TBHP/I₂-Promoted Oxidative Coupling of Azoles with Benzyl Compounds via Cleavage of Nonactivated C(sp³)–H Bonds under Solvent-Free Conditions

Abstract

A novel and efficient TBHP/I₂-promoted oxidative coupling of azoles with benzyl compounds via cleavage of nonactivated C(sp³)–H bonds under metal-free, base-free, and solvent-free conditions for the synthesis of N-alkylated azoles has been developed. The procedure, using I₂ as the catalyst, is a simple, economical, and environmentally friendly protocol, which could be applied to various available substrates in moderate to good yields.

Key words

solvent-free - metal-free - oxidative coupling - N-alkylated azoles - free-radical reaction

• References

• 1a Soderlind KJ, Gorodetsky B, Singh AK, Bachur N, Miller GG, Lown JW. Anticancer Drug Des. 1999; 14: 19
• 1b Woynarowski JM, McHugh MM, Sigmud RD, Beerman TA. Mol. Pharmacol. 1989; 35: 177
• 1c Nakano H, Inoue T, Kawasaki N, Miyataka H, Matsumoto H, Taguchi T, Inagaki N, Nagai H, Satoh T. Bioorg. Med. Chem. 2000; 8: 373
• 1d Horton DA, Bourne GT, Smythe ML. Chem. Rev. 2003; 103: 893
• 1e Kosano H, Kayanuma T, Nishigori H. Biochem. Biophys. Acta 2000; 1499: 11
• 2a Butler MS. J. Nat. Prod. 2004; 67: 2141
• 2b Joule JA, Mills K. Heterocyclic Chemistry . Vol. 8. Blackwell Science; Oxford: 2000: 231
• 2c Asensio JA, Gomez-Romero P. Fuel Cells 2005; 5: 336
• 3 Schwartz G, Fehse K, Pfeiffer M, Walzer K, Leo K. Appl. Phys. Lett. 2006; 89: 083509
• 4a Al-Azmi A, George P, El-Dusouqui OM. E. J. Heterocycl. Chem. 2007; 44: 515
• 4b Begtrup M, Larsen P. Acta Chem. Scand. 1990; 44: 1050
• 4c Jeletic MS, Jan MT, Ghiviriga I, Abboud KA, Veige AS. Dalton Trans. 2009; 2764
• 5a Murru S, Patel BK, Bras JL, Muzart J. J. Org. Chem. 2009; 74: 2217
• 5b Monguchi D, Fujiwara T, Furukawa H, Mori A. Org. Lett. 2009; 11: 1607
• 5c Wang Q, Schreiber SL. Org. Lett. 2009; 11: 5178
• 5d Yang F, Xu Z, Wang Z, Yu Z, Wang R. Chem. Eur. J. 2011; 17: 6321
• 5e Liang Y.-M, Liu X.-Y, Gao P, Shen Y.-W. Org. Lett. 2011; 13: 16
• 5f Matsuda N, Hirano K, Satoh T, Miura M. Org. Lett. 2011; 13: 2860
• 5g Hamada T, Ye X, Stahl SS. J. Am. Chem. Soc. 2008; 130: 833
• 5h Chen L, Shi E, Liu Z, Chen S, Wei W, Li H, Xu K, Wan X. Chem. Eur. J. 2011; 12: 4085
• 6a Stuart DR, Fagnou K. Science 2007; 316: 1172
• 6b Stuart DR, Villemure E, Fagnou K. J. Am. Chem. Soc. 2007; 129: 12072
• 6c Truong T, Daugulis O. J. Am. Chem. Soc. 2011; 133: 4243
• 6d Cao H, Zhan HY, Lin YG, Lin XL, Du ZD, Jiang HF. Org. Lett. 2012; 14: 1688
• 6e Suarez LL, Greaney MF. Chem. Commun. 2011; 47: 7992
• 6f Zhu YP, Liu MC, Jia FC, Yuan JJ, Gao QH, Lian M, Wu AX. Org. Lett. 2012; 14: 3392
• 7 Xia Q, Chen W, Qiu H. J. Org. Chem. 2011; 76: 7577
• 8a Yadav JS. B, Reddy VS, Premalatha K, Swamy T. Tetrahedron Lett. 2005; 46: 2687
• 8b Zeng LY, Cai C. J. Comb. Chem. 2010; 12: 35
• 8c Zeng L.-Y, Cai C. Org. Biomol. Chem. 2010; 8: 4803
• 8d Wang XS, Li Q, Wu JR, Li YL, Yao CS, Tu SJ. Synthesis 2008; 1902
• 8e Yue D, Yao T, Larock RC. J. Org. Chem. 2006; 71: 62
• 8f Zhang X, Campo MA, Yao T, Larock RC. Org. Lett. 2005; 7: 763
• 8g Yue D, DellaCa N, Larock RC. J. Org. Chem. 2006; 71: 3381
• 8h Kim J.-G, Jang DO. Synlett 2010; 2093
• 9a Li J, Wang D, Zhang Y, Li J, Chen B. Org. Lett. 2009; 11: 3024
• 9b Li J, Zhang Y, Wang D, Wang W, Gao T, Wang L, Li J, Huang G, Chen B. Synlett 2010; 1617
• 9c Meng X, Xu X, Gao T, Chen B. Eur. J. Org. Chem. 2010; 5409
• 9d Li N, Wang D, Li J, Shi W, Li C, Chen B. Tetrahedron Lett. 2011; 52: 980
• 10 Chen W, Yan R, Tang D, Guo S, Meng X, Chen B. Tetrahedron 2012; 68: 7956
• 11 General Procedure of the Reaction between Azoles and Toluenes – Synthesis of 1-Benzyl-1H-benzo[d][1,2,3]triazole (3aa) All reactions were performed on a 0.50 mmol scale relative to azoles. The benzotriazole (1a, 0.50 mmol), toluene (2a, 2.0 mmol), I₂ (0.050 mmol), and TBHP (2 equiv) were taken in a round-bottom flask equipped with a stirrer. The resulting mixture was stirred for 8 h at 100 °C. After cooling to r.t., to the reaction mixture was added H₂O (2 mL) and extracted with ester (3 × 10 mL). The combined organic phases were washed with brine (2 × 5 mL), dried over anhyd MgSO₄, and concentrated in vacuo. The residue was subjected to flash column chromatography with hexanes–EtOAc (10:1) as eluent to obtain the desired 3aa a light yellow solid (90% yield). The remaining substituted triazoles were prepared in the similar manner and their characterization data are as follows. Compound 3aa was purified by flash chromatography (hexane–EtOAc = 10:1, v/v) as light yellow solid (yield 90%), mp 113–115 °C. ¹H NMR (300 MHz, CDCl₃): δ = 8.04–8.06 (d, J = 7.8 Hz, 1 H), 7.25–7.38 (m, 8 H), 5.82 (s, 2 H). ¹³C NMR (100 MHz, CDCl₃): δ = 146.2, 134.7, 132.7, 128.9, 128.3, 127.5, 127.3, 123.8, 119.9, 109.6, 52.1.