Synlett 2014; 25(09): 1267-1270
DOI: 10.1055/s-0033-1341229
letter
© Georg Thieme Verlag Stuttgart · New York

One-Pot, Sequential Four-Component Synthesis of Thiazepine Derivatives

Abdolali Alizadeh*
a  Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: aalizadeh@modares.ac.ir   Email: abdol_alizad@yahoo.com
,
Masoomeh Feizabadi
a  Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: aalizadeh@modares.ac.ir   Email: abdol_alizad@yahoo.com
,
Fahimeh Bayat
a  Department of Chemistry, Tarbiat Modares University, P.O. Box 14115-175, Tehran, Iran   Fax: +98(21)88006544   Email: aalizadeh@modares.ac.ir   Email: abdol_alizad@yahoo.com
,
Long-Guan Zhu
b  Department of Chemistry, Zhejiang University, Hangzhou 310027, P. R. of China
› Author Affiliations
Further Information

Publication History

Received: 21 February 2014

Accepted after revision: 24 March 2014

Publication Date:
10 April 2014 (online)

Abstract

A one-pot, sequential, four-component procedure for the synthesis of thiazepines by the reaction of primary amines, 1,3-dicarbonyl compounds, aryl isothiocyanates, and chloroacetyl chloride at room temperature is described. Advantages of this protocol include ease of handling, regioselectivity, the absence of a metal catalyst, and moderate yields.

Supporting Information

 
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  • 16 Thiazepines 5ah; General Procedure A mixture of primary amine 1 (1 mmol) and 1,3-dicarbonyl compound 2 (1 mmol) was stirred at r.t. for 0.5 h. Aryl isothiocyanate 3 (1 mmol) was then added and the mixture was stirred for another 6 h. Subsequently, a soln of ClCH2COCl (1 mmol) in MeCN (3 mL) was added. When the reaction was complete (1.5 h, TLC), the solvent was removed under reduced pressure and the residue was purified by column chromatography (hexane–EtOAc, 5:1). Methyl 5-Methyl-3-oxo-7-(phenylimino)-4-propyl-2,3,4,7-tetrahydro-1,4-thiazepine-6-carboxylate (5a) Pale-yellow powder; yield: 0.26 g (78%); mp 137–139 °C; IR (KBr): 1726 (CO2Me), 1668 (NCO), 1640 (SC=N), 1586, 1482 and 1441 (Ar), 1273 (C–O) cm–1; 1H NMR (300 MHz, DMSO-d 6): δ = 0.87 (t, 3 J HH = 6.3 Hz, 3 H, CH 3CH2CH2N), 1.37–1.48 (m, 2 H, CH3CH 2CH2N), 2.26 (s, 3 H, Me), 3.11 (dt, 2 J HH = 13.1 Hz, 3 J HH = 6.4 Hz, 1 H, CH2N), 3.22 (d, 2 J HH = 13.2 Hz, 1 H, SCH2CO), 3.76 (s, 3 H, OMe), 3.93 (dt, 2 J HH = 13.1 Hz, 3 J HH = 6.4 Hz, 1 H, CH2N), 4.14 (d, 2 J HH = 13.2 Hz, 1 H, SCH2CO), 6.71 (d, 3 J HH = 6.8 Hz, 2 H, 2 × CH ortho of Ph), 7.14 (t, 3 J HH = 6.2 Hz, 1 H, CH para of Ph), 7.38 (t, 3 J HH = 6.8 Hz, 2 H, 2 × CH meta of Ph); 13C NMR (75 MHz, DMSO-d 6): δ = 11.0 (CH3), 18.7 (CH3), 21.1 (CH2), 32.6 (CH2S), 43.9 (CH2N), 52.4 (OMe), 118.8 (2 × CH ortho of Ph), 124.9 (CH para of Ph), 125.1 (C ipso ), 129.4 (2 × CH meta of Ph), 149.5 (C6), 149.6 (C7), 160.9 (C5), 165.7 (CO2Me), 167.3 (NCO); MS (EI, 70 eV): m/z = 333 [M + 1]+, 332 [M+], 229, 200, 187, 158, 142, 116, 84, 77, 51; Anal. Calcd for C17H20N2O3S: C, 61.43; H, 6.06; N, 8.43. Found: C, 61.37; H, 6.11; N, 8.50. Crystal data: C17H20N2O3S: MW = 332.42, orthorhombic, space group Pna21, a = 17.3838(8) Å, b = 14.3978(6) Å, c = 6.9357(3) Å, V = 1735.93(13) Å3, Z = 4, Dc = 1.272 Mg/m3, F(000) = 704; crystal dimensions: 0.38 × 0.26 × 0.23 mm; radiation: Mo Kα (λ = 0.71073Å), 3.06 ≤ 2θ ≤ 25.09. Intensity data were collected at 295(2) K with a Bruker APEX area-detector diffractometer, employing the ω/2θ scanning technique, in the range –20 ≤ h ≤ 20, –17 ≤ k ≤ 17, –8 ≤ l ≤ 8. The structure was solved by a direct method; all nonhydrogen atoms were positioned and anisotropic thermal parameters were refined from 3048 observed reflections with R(int) = 0.0500 by a full-matrix least-squares technique converging to R = 0.0399 and Rw = 0.1080 [I > 2σ(I)].
  • 17 Crystallographic data for compound 5a have been deposited with the accession number CCDC 971337, and can be obtained free of charge from the Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EZ, UK; Fax: +44(1223)336033; E-mail: deposit@ccdc.cam.ac.uk; Web site: www.ccdc.cam.ac.uk/conts/retrieving.html.