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Synlett 2011(7): 979-981  
DOI: 10.1055/s-0030-1259720
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

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

Li-Feng Liua, Na Ana, Hong-Jun Pia, Jun Yinga, Wenting Du*a,b, Wei-Ping Deng*a
a School of Pharmacy, East China University of Science and Technology, 130 Meilong Road, Shanghai 200237, P. R. of China
Fax: +86(21)64252431; e-Mail: weiping_deng@ecust.edu.cn; Fax: +86(21)64252431; e-Mail: ddwwtt@163.com;
b Department of Pharmacy, Zhejiang Medical College, 481 Binwen Road, Hangzhou 310053, P. R. of China
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Publication History

Received 26 October 2010
Publication Date:
10 March 2011 (online)

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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.

Key words

Beckmann rearrangement - thioamides - tosyl chloride - ketoximes

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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.