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Synlett 2004(12): 2200-2202  
DOI: 10.1055/s-2004-831302
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of 2-Alkylidene-4-(hydroxymethyl)thiazolidines by One-Pot Cyclization of Dilithiated Arylmethylnitriles with Isothiocyanates and Epibromohydrin

Uwe Albrecht, Peter Langer*
Institut für Chemie und Biochemie, Ernst-Moritz-Arndt-Universität Greifswald, Soldmannstr. 16, 17487 Greifswald, Germany
e-Mail: peter.langer@uni-greifswald.de;
Further Information

Publication History

Received 15 June 2004
Publication Date:
26 August 2004 (online)

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Abstract

2-Alkylidene-(4-hydroxymethyl)thiazolidines were regioselectively prepared by one-pot cyclization of dilithiated aryl­methylnitriles with isothiocyanates and epibromohydrin.

Key words

cyclizations - epoxides - N-heterocycles - isothiocyanates - one-pot reactions

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18

Typical Procedure for the Preparation of (4-Hydroxymethyl)thiazolidines: To a THF solution (10 mL) of 4-tolylmethylnitrile 1c (0.262 g, 2.0 mmol) was added n-BuLi (4.4 mmol, 1.6 M) at 0 °C. After stirring for 1 h, ethylisothiocyanate (2d, 0.174 g, 2.0 mmol) was added and the solution was stirred for 1 h at 0 °C. Subsequently, epibromohydrin (0.274 g, 2.0 mmol) was added. After warming to 20 °C during 16 h, an aqueous solution of HCl (20 mL, 1 M) was added. The organic and the aqueous layers were separated and the latter was extracted with EtOAc (3 × 30 mL). The combined organic layers were extracted with brine (30 mL), dried (Na2SO4), filtered and the solvent of the filtrate was removed in vacuo. The residue was purified by chromatography (silica gel, hexane-EtOAc, 3:2) to give 4n as colorless oil (0.491 g, 90%, E/Z = 5:1). 1H NMR (300 MHz, CDCl3, signals are given for both E/Z isomers): δ = 0.97, 1.27 (2 × t, 3 J = 7 Hz, 3 H, CH3), 2.28, 2.30 (2 × s, 3 H, CH3), 2.94-3.22 (m, 3 H, CH, CH2), 3.56-3.66 (m, 2 H, CH2), 3.94-4.08 (m, 2 H, CH2), 7.09 (d, 3 J = 8 Hz, 2 H, CH), 7.28 (d, 3 J = 8 Hz, 2 H, CH). 13C NMR (75 MHz, CDCl3, signals are given for both E/Z isomers): δ = 12.53, 13.43, 20.74, 21.89 (CH3), 27.49, 29.39, 43.93, 45.15, 60.30, 60.87 (CH2), 68.48, 68.57 (CH), 70.88, 73.87, 121.24, 123.47 (C), 127.87, 128.75, 128.76, 128.99 (CH), 130.62, 133.61, 135.78, 136.29, 161.23, 162.62 (C). IR (KBr): 3432 (s), 2975 (w), 2934 (m), 2873 (w), 2177 (s), 1645 (w), 1548 (s), 1461 (m), 1444 (m) cm-1. MS (EI, 70 eV): m/z (%) = 274 (100) [M+], 243 (84), 215 (46), 188 (14), 119 (33); the exact molecular mass for C15H18N2OS m/z = 274.1140 ± 2mD (M+) was confirmed by HRMS (EI, 70 eV). All new compounds gave satisfactory spectroscopic and correct analytical and/or high resolution mass data.