Synlett 2017; 28(14): 1795-1800
DOI: 10.1055/s-0036-1588419
letter
© Georg Thieme Verlag Stuttgart · New York

Metal-Free Mediated C-3 Methylsulfanylation of Imidazo[1,2-a]-pyridines with Dimethyl Sulfoxide as a Methylsulfanylating Agent

Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China   Email: zkchen@zstu.edu.cn   Email: renhj@zstu.edu.cn
,
Gangjian Cao
Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China   Email: zkchen@zstu.edu.cn   Email: renhj@zstu.edu.cn
,
Fengjin Zhang
Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China   Email: zkchen@zstu.edu.cn   Email: renhj@zstu.edu.cn
,
Hongli Li
Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China   Email: zkchen@zstu.edu.cn   Email: renhj@zstu.edu.cn
,
Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China   Email: zkchen@zstu.edu.cn   Email: renhj@zstu.edu.cn
,
Maozhong Miao
Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China   Email: zkchen@zstu.edu.cn   Email: renhj@zstu.edu.cn
,
Hongjun Ren*
Department of Chemistry, Zhejiang Sci-Tech University, Hangzhou 310018, P. R. of China   Email: zkchen@zstu.edu.cn   Email: renhj@zstu.edu.cn
› Author Affiliations
We thank the National Nature Science Foundation of China (Grant No. 21602202), the Science Foundation of Zhejiang Sci-Tech University (Grant Nos. 15062092-Y, 1206820-Y, and 1206821-Y), and the Zhejiang Provincial Top Key Academic Discipline of Chemical Engineering and Technology of Zhejiang Sci-Tech University for their financial support.
Further Information

Publication History

Received: 01 March 2017

Accepted after revision: 18 April 2017

Publication Date:
10 May 2017 (online)


Abstract

A simple approach is described for the regioselective C-3 methylsulfanylation of imidazo[1,2-a]pyridines through diiodine-­mediated, acetone-promoted, C–S bond construction with dimethyl sulfoxide as both the source of the methylsulfanyl moiety and the solvent. Preliminary mechanistic investigations indicated that three different reaction mechanisms might be involved in the transformation.

Supporting Information

 
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  • 11 3-(Methylsulfanyl)-2-phenylimidazo[1,2-a]pyridine (2a); Typical Procedure I2 (152 mg, 0.6 mmol) and acetone (35 mg, 0.6 mmol) were added to a solution of substrate 1a (0.3 mmol) in DMSO (1 mL), and the mixture was stirred at 100 °C under air for 12 h. When the reaction was complete (TLC), the mixture was cooled to r.t., the reaction was quenched by H2O, and the mixture was extracted with EtOAc (3 × 15 mL). The extracts were washed with 10% aq Na2S2O3 (2 × 15 mL), dried (Na2SO4), and concentrated in vacuo. The resulting crude product was purified by column chromatography (silica gel, PE–EtOAc) to give a brown-yellow solid; yield: 53 mg (74%); mp 65–67 °C. 1H NMR (400 MHz, CDCl3): δ = 8.49 (d, J = 6.8 Hz, 1 H), 8.29 (m, 2 H), 7.68 (d, J = 9.2 Hz, 1 H), 7.49 (t, J = 7.6 Hz, 2 H), 7.39 (m, 1 H), 7.30 (m, 1 H), 6.94 (td, J1 = 6.8, J2 = 0.8 Hz, 1 H), 2.26 (s, 3 H). 13C NMR (100 MHz, CDCl3): δ = 148.7, 146.3, 133.7, 128.4, 128.3, 128.2, 126.0, 124.2, 117.6, 112.7, 111.4, 18.1. HRMS (ES+–TOF): m/z [M + H]+ calcd for C14H13N2S: 241.0799; found: 241.0799.
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