Facile and Odorless One-Pot Process for the Synthesis of N-Substituted Thioamides via TsCl-Mediated Beckmann Rearrangement of Ketoximes

Abstract

A facile and odorless one-pot thionation process for the synthesis of N-substituted thioamides using chemically stable and inexpensive thiourea reagent via the Beckmann rearrangement of ketoximes, has been described.

Beckmann rearrangement - thioamides - tosyl chloride - ketoximes

References and Notes

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15

General Procedure for the Synthesis of Thioamides: To a solution of the ketoxime (2 mmol) and Et₃N (0.62 mL, 4.4 mmol) in anhyd MeCN (5 mL) under a nitrogen atmosphere was added TsCl (2.2 mmol) in an ice bath. After stirring at r.t. for 30 min, thiourea (4 mmol) was added and the resulting mixture was then refluxed for 2 h. After the reaction was finished (monitored by TLC), it was quenched by brine. The organic layer was extracted with CH₂Cl₂, and dried over anhyd Na₂SO₄. After evaporation of the organic layer under reduced pressure, the resulting crude product was purified by column chromatography on silica gel to give the corresponding thioamides in moderate to high yields. All products gave satisfactory analytical data and are consistent with published data.⁸ The data for selected compound 2a: mp 75-76 ˚C (lit.⁸ 75-76 ˚C). ^¹H NMR (400 MHz, CDCl₃): δ = 9.51 (br s, 1 H), 8.71 (br s, 1.2 H), 7.67 (d, J = 7.7 Hz, 2.4 H), 7.48-7.33 (m, 5.5 H), 7.29 (d, J = 7.4 Hz, 1 H), 7.18 (d, J = 7.6 Hz, 2 H), 2.75 (s, 3.6 H), 2.52 (s, 3 H). ^¹³C NMR (100 MHz, CDCl₃): δ = 204.0, 200.7, 138.6, 137.9, 129.7, 128.9, 128.1, 127.1, 125.1, 124.3, 35.4, 30.3.