Simple Synthesis of Sulfonyl Chlorides from Thiol Precursors and Derivatives by NaClO₂-Mediated Oxidative Chlorosulfonation

Abstract

A simple method to synthesize diverse sulfonyl chlorides through NaClO₂-mediated oxidative chlorosulfonation of S-alkyl isothiourea salts is presented. The approach features safe operation, environmental friendliness, convenient purification procedures, and delivers high yields of up to 96%. The procedure is also applicable to substrates such as thiols, disulfides, thioacetates, and xanthates. It is a versatile and convenient method for the synthesis of various sulfonyl chlorides from different thiol precursors and derivatives.

Key words

sulfonyl chloride - sodium chlorite - oxidative chlorosulfonation - synthetic methods - isothiourea

• References and Notes

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Chlorine and N-chlorosuccinimide were used to realize the chlorosulfonation of S-alkyl isothiourea salts, see:
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• 9 Synthesis of 3e; Typical Procedure: (1) p-Chlorobenzyl chloride 1e (0.805 g, 5 mmol) and thiourea (0.381 g, 5 mmol) were heated at reflux in EtOH (5 mL) for 1 h. After removal of the solvent under vacuum S-p-chlorobenzyl isothiouronium chloride (2e) was obtained as a white solid in quantitative yield. (2) A 50-mL three-necked flask equipped with a thermometer and a solid-addition funnel was immersed in an ice-bath. To the flask was sequentially added solid NaClO₂ (1.61 g, 15 mmol, 85% purity), MeCN (10 mL), and then concd HCl (3 mL) during 1 min, keeping the inner temperature below 10 °C. Then 2e was slowly added through the solid-addition funnel to keep the inner temperature below 20 °C. After the addition, the resulting mixture was stirred for another 30 min, then H₂O (25 mL) was added, and the resultant mixture was evaporated in vacuum at 15 °C to remove MeCN. After addition of H₂O (100 mL), filtration on a Büchner funnel and drying under an infrared lamp, 3e was afforded as colorless crystals. Yield: 1.080 g (96%); mp 91–93 °C (Lit.^6c 90–92 °C). ¹H NMR (400 MHz, CDCl₃): δ = 7.46–7.41 (m, 4 H), 4.83 (s, 2 H); ¹³C NMR (101 MHz, CDCl₃): δ = 136.8, 132.6, 129.5, 124.6, 70.0.