Copper-Catalyzed Direct Synthesis of Aryl Thiols from Aryl Iodides Using Sodium Sulfide Aided by Catalytic 1,2-Ethanedithiol

Abstract

A copper-catalyzed direct and effective synthesis of aryl thiols from aryl iodides using readily available Na₂S·9H₂O and 1,2-ethanedithiol was described. A variety of aryl thiols were readily obtained in yields of 76–99%. In this protocol, Na₂S·9H₂O was used as ultimate sulfur source, and 1,2-ethanedithiol functioned as an indispensable catalytic reagent.

Key words

aryl thiols - copper - sodium sulfide - 1,2-ethanedithiol - thiolation

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• 21 General Experimental Procedure for the Synthesis of Aryl Thiols from Aryl Iodides To a test tube containing a magnetic bar was added aryl iodide (1 mmol), copper powder (6.35 mg, 0.1 mmol), Na₂S·9H₂O (720.54 mg, 3 mmol), and DMSO (2 mL). After flushing with argon, 1,2-ethanedithiol (8.4 μL, 0.1 mmol) was added. The mixture was stirred in the oil bath at 100 °C for 20 h. After cooled to ambient temperature, the reaction mixture was distributed in aq HCl (5%) and EtOAc. The organic layer was separated and washed with water and brine, dried, and concentrated under vacuum. The crude product was further purified by column chromatography using ethyl acetate/n-hexane as eluent to provide the desired aryl thiol. Analytical Data of Representative Compounds 4-Methylbenzenethiol (2a) ¹⁹ Yield 97%; white solid. ¹H NMR (500 MHz, CDCl₃): δ = 7.19 (d, J = 8.1 Hz, 2 H), 7.06 (d, J = 8.0 Hz, 2 H), 3.39 (s, 1 H), 2.31 (s, 3 H). ¹³C NMR (126 MHz, CDCl₃): δ = 135.6, 129.8, 129.8, 126.5, 20.9. 4-Methoxybenzenethiol (2h) ¹⁹ Yield 93%; yellow liquid. ¹H NMR (500 MHz, CDCl₃): δ = 7.18 (d, J = 8.5 Hz, 2 H), 6.72 (d, J = 8.8 Hz, 2 H), 3.70 (s, 3 H), 3.28 (s, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 158.5, 132.4, 119.8, 114.7, 55.3. 4-Mercaptobenzoic Acid (2n)¹⁹ Yield 99%; white powder. ¹H NMR (500 MHz, CDCl₃): δ = 7.96 (d, J = 7.5 Hz, 2 H), 7.32 (d, J = 7.6 Hz, 2 H), 3.65 (s, 1 H). ¹³C NMR (126 MHz, CDCl₃): δ = 171.1, 139.8, 130.8, 128.1, 126.1.