Exploration of Copper(II) Acetate Catalyzed Regioselective Ethoxylation of o-Haloanilides with Picolinamide as a Directing Group

Abstract

An efficient Cu-catalyzed Ullmann-type C–O coupling of o-haloanilides was developed. This method permits regioselective 2-ethoxylation of N-(2-bromoaryl)- or N-(2-iodoaryl)picolinamides in ethanol with Cu(OAc)₂ as a convenient catalyst and with picolinamide as a directing group and intramolecular ligand. The reaction is characterized by good regioselectivity, high yields, and the absence of the need for an additional ligand.

Key words

copper catalysis - Ullmann coupling - ethoxylation - haloanilides - picolinamides

Publication History

Received: 05 September 2022

Accepted after revision: 17 October 2022

Accepted Manuscript online:
17 October 2022

Article published online:
15 December 2022

• References and Notes

• 1a Zhu R, Sun Q, Li J, Li L, Gao Q, Wang Y, Fang F. Chem. Commun. 2021; 57: 13190
• 1b Carmona E, Paneque M, Santos LL, Salazar V. Coord. Chem. Rev. 2005; 249: 1729
• 1c Zhang Y, Geng Z, Niu S, Zhang S, Luan J, Wang G. Adv. Ind. Eng. Polym. Res. 2020; 3: 175
• 2a Dou X, Li W, Zhu C, Jiang X, Chang H.-m, Jameel H. RSC Adv. 2020; 10: 43599
• 2b Lindstedt E, Ghosh R, Olofsson B. Org. Lett. 2013; 15: 6070
• 2c Chen G, Du J. Youji Huaxue 2014; 34: 65
• 3 Tobisu M, Chatani N. Acc. Chem. Res. 2015; 48: 1717
• 4a Aranyos A, Old DW, Kiyomori A, Wolfe JP, Sadighi JP, Buchwald SL. J. Am. Chem. Soc. 1999; 121: 4369
• 4b Lam PY. S, Vincent G, Clark CG, Deudon S, Jadhav PK. Tetrahedron Lett. 2001; 42: 3415
• 5a Joseph PJ. A, Priyadarshini S. Org. Process Res. Dev. 2017; 21: 1889
• 5b Sun C.-L, Shi Z.-J. Chem. Rev. 2014; 114: 9219
• 5c Qiao S, Deng W, Deng G, Liang Y, Yang Y. Org. Biomol. Chem. 2022; 20: 6275
• 6 Rouzifar M, Sobhani S, Farrokhi A, Sansano JM. New J. Chem. 2021; 45: 19963
• 7 Enthaler S, Company A. Chem. Soc. Rev. 2011; 40: 4912
• 8 Majumder A, Gupta R, Mandal M, Babu M, Chakraborty D. J. Organomet. Chem. 2015; 781: 23
• 9 Garnier T, Danel M, Magné V, Pujol A, Bénéteau V, Pale P, Chassaing S. J. Org. Chem. 2018; 83: 6408
• 10 Milton EJ, Fuentes JA, Clarke ML. Org. Biomol. Chem. 2009; 7: 2645
• 11 Yamakawa K. US 5006660, 1991
• 12 Ma D, Xie S, Xue P, Zhang X, Dong J, Jiang Y. Angew. Chem. Int. Ed. 2009; 48: 4222
• 13 Jadhav J, Gaikwad V, Kurane R, Salunkhe R, Rashinkar G. Tetrahedron 2013; 69: 2920
• 14a Li Q, Zhang S.-Y, He G, Ai Z, Nack WA, Chen G. Org. Lett. 2014; 16: 1764
• 14b Yang Q.-L, Wang X.-Y, Lu J.-Y, Zhang L.-P, Fang P, Mei T.-S. J. Am. Chem. Soc. 2018; 140: 11487
• 14c Shen J, Xu J, Cai H, Shen C, Zhang P. Org. Biomol. Chem. 2019; 17: 490
• 14d Martínez ÁM, Rodríguez N, Arrayás RG, Carretero JC. Chem. Commun. 2014; 50: 2801
• 15 Damkaci F, Altay E, Waldron M, Knopp MA, Snow D, Massaro N. Tetrahedron Lett. 2014; 55: 690
• 16 Li M.-X, Li M.-L, Tang Y.-L, Sun Y, Qu L, Huang F, Mao Z.-W. J. Organomet. Chem. 2021; 943: 121844
• 17 Li Q, Huang J, Chen G, Wang S.-B. Org. Biomol. Chem. 2020; 18: 4802
• 18 Ethoxylation of o-Haloanilides; General Procedure A stirred solution of the appropriate o-haloanilide 1 (1 mmol), Cu(OAc)₂ (20 mg, 0.1 mmol), and K₂CO₃ (276 mg, 2 mmol) in EtOH (10 mL) was stirred at 100 °C for 8–12 h. When the reaction was complete (TLC), the mixture was concentrated in vacuo, and the residue was purified by column chromatography [silica gel, PE–EtOAc (5:1)]. N-(2-Ethoxyphenyl)picolinamide (2a) Prepared according to the general procedure from 1a or 1a′ as a pale-yellow thick liquid; yield: 85 or 90%, respectively. ¹H NMR (400 MHz, CDCl₃): δ = 10.67 (s, 1 H), 8.63 (d, J = 5.7 Hz, 2 H), 8.29 (d, J = 7.8 Hz, 1 H), 7.85–7.88 (m, 1 H), 7.41–7.44 (m, 1 H), 6.99–7.08 (m, 1 H), 6.92 (d, J = 7.8 Hz, 1 H), 4.18 (q, J = 7.0 Hz, 2 H), 1.53 (t, J = 7.0 Hz, 3 H). ¹³C NMR (100 MHz, CDCl₃): δ = 162.06, 150.49, 148.28, 148.20, 137.49, 127.94, 126.22, 123.97, 122.30, 121.09, 119.74, 111.50, 64.51, 14.91.