Transition-Metal-Free Method for the Synthesis of Benzo[b]thiophenes from o-Halovinylbenzenes and K₂S via Direct S_NAr-Type Reaction, Cyclization, and Dehydrogenation Process

Abstract

A new, highly efficient procedure for the synthesis of benzothiophenes from easily available o-halovinylbenzenes and potassium sulfide has been developed. The reaction tolerated a wide range of functionalities, and various 2-substituted benzo[b]thiophenes are provided in the high yields in the absence of a transition-metal catalyst.

Key words

transition-metal-free - benzo[b]thiophenes - o-halo­vinylbenzenes - direct S_NAr-type reaction - cyclization - dehydrogenation process

• References and Notes

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• 10 Benzo[b]thiophenes 2; General Procedure Under the protection of nitrogen, an oven-dried Schlenk tube was charged with K₂S (0.9 mmol, 3 equiv) and the 1-fluoro-2-styryl derivative (0.3 mmol). The tube was evacuated and backfilled with nitrogen before DMF or MeCN (2 mL) was added. The reaction mixture was stirred at 140 °C, and after 24 h was quenched with H₂O. The mixture extracted with EtOAc, and the combined organic layers were washed with H₂O and brine, dried over Na₂SO₄, concentrated in vacuo and purified by column chromatography to afford the product. Analytical Data for Compound 2a white solid; isolated yield 96% (60 mg; mp 172.2–173.0 °C. ¹H NMR (500 MHz, CDCl₃): δ = 7.82 (d, J = 8.0 Hz, 1 H), 7.77 (d, J = 7.5 Hz, 1 H), 7.72 (d, J = 8.5 Hz, 2 H), 7.54 (s, 1 H), 7.42 (t, J = 7.8 Hz, 2 H), 7.36–7.29 (m, 3 H). ¹³C NMR (125 MHz, CDCl₃): δ = 144.2, 140.7, 139.5, 134.3, 128.9, 128.2, 126.5, 124.5, 124.3, 123.5, 122.2, 119.4.