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Regioselective C-H Thiocyanation of Arenes by Iron(III) Chloride Catalysis

Lachlan J. N. Waddell, Maisie R. Senkans and Andrew Sutherland*

*School of Chemistry, The Joseph Black Building, University of Glasgow, Glasgow G12 8QQ, U.K., Email: Andrew.Sutherlandglasgow.ac.uk

L. J. N. Waddell, M. R. Senkrans, A. Sutherland, J. Org. Chem., 2023, 88, 7208-7218.

DOI: 10.1021/acs.joc.3c00454



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Abstract

Iron(III) chloride is an effective Lewis acid for the activation of N-thiocyanatosaccharin and the subsequent thiocyanation of a wide range of activated arenes. The procedure was applicable for the thiocyanation of biologically active compounds such as metaxalone and an estradiol derivative.


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General Procedure: 4-Thiocyanatoanisole

To a solution of N-thiocyanatosaccharin (0.0960 g, 0.400 mmol) and iron(III) chloride (0.00135 g, 0.00832 mmol, 2.5 mol %) in dry dichloromethane (2 mL) under argon was added anisole (0.0362 mL, 0.333 mmol). The reaction mixture was stirred at 40 C in the absence of light for 0.5 h. After cooling to room temperature, the reaction mixture was diluted with dichloromethane (10 mL) and washed with water (10 mL). The aqueous layer was extracted with dichloromethane (2 10 mL), and the combined organic layers were washed with brine (20 mL). The organic phase was dried (MgSO4), filtered, and concentrated in vacuo. Purification by flash column chromatography (15% diethyl ether in hexane) gave 4-thiocyanatoanisole (0.0514 g, 93%) as a colorless oil. Spectroscopic data were consistent with the literature. 1H NMR (CDCl3, 400 MHz): δ 7.53-7.48 (m, 2H), 6.97-6.93 (m, 2H), 3.83 (s, 3H); 13C{1H} NMR (CDCl3, 101 MHz): δ 161.5 (C), 134.0 (2 CH), 116.0 (2 CH), 114.0 (C), 111.8 (C), 55.7 (CH3); MS (ESI) m/z 166 (M + H+, 100).


Key Words

thiocyanation


ID: J42-Y2023