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

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

References and Notes

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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.