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Synlett 2007(3): 0465-0469  
DOI: 10.1055/s-2007-968027
LETTER
© Georg Thieme Verlag Stuttgart · New York

New Benzothiazole and Benzoxazole Scaffolds from the Ugi-Smiles Couplings of Heterocyclic Thiols

Laurent El Kaim*, Marie Gizolme, Laurence Grimaud*, Julie Oble
Laboratoire Chimie et Procédés, Ecole Nationale Supérieure de Techniques Avancées, 32 Bd Victor, 75739 Paris Cedex 15, France
Fax: +33(1)45525587; e-Mail: laurent.elkaim@ensta.fr; e-Mail: laurence.grimaud@ensta.fr;
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Publication History

Received 13 November 2006
Publication Date:
07 February 2007 (online)

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Abstract

New four-component benzoxazole and benzothiazole scaffolds were obtained via an Ugi-Smiles coupling of 2-mercapto benzoxazole and 2-mercapto benzothiazole derivatives with isocyanides, aldehydes and primary amines. The 2-mercapto benzimidazoles tested were not reactive under similar conditions as well as the analogous 2-hydroxy benzoxazoles and 2-hydroxy benzothiazoles.

Key words

benzothiazole - benzoxazole - multicomponent reaction - thioamides

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11

Preparation of Thioamide 4b; Typical Procedure To a 1 M solution of carbonyl compound 1b in toluene were added the amine 2a (1.0 equiv), the isocyanide 3a (1.0 equiv)and the mercapto benzoxazole (1.0 equiv). The resulting mixture was stirred at 50 °C under an inert atmosphere for 2 d and concentrated in vacuo. The crude product was then purified by flash chromatography on silica gel to give the desired adduct 4b.
1H NMR (400 MHz, CDCl3): δ = 10.00 (br s, 1 H), 7.38-7.28 (m, 6 H), 7.24 (td, 1 H, J = 7.8, 1.3 Hz), 7.12 (td, 1 H, J = 7.8, 1.3 Hz), 4.96 (d, 1 H, J = 16.2 Hz), 4.76 (d, 1 H, J = 16.2 Hz), 4.53 (t, 1 H, J = 7.6 Hz), 2.36-2.24 (m, 1 H), 2.12-2.02 (m, 1 H), 1.52 (s, 9 H), 0.82 (t, 3 H, J = 7.3 Hz). 13C NMR (100.6 MHz, CDCl3): δ = 199.2, 162.8, 148.9, 142.3, 136.5, 133.9, 129.7, 129.1, 124.8, 121.8, 116.5, 109.7, 74.1, 56.0, 51.7, 27.5, 24.2, 11.3. IR (thin film): 2965, 2930, 2349, 1625, 1563, 1458, 1362, 1245, 1210, 1014 cm-1. MS (DI, CI NH3): m/z = 416 [M + H+]. HRMS: m/z calcd for C22H26ClN3OS: 415.1485; found: 415.1471.