Efficient Microwave Enhanced Synthesis of 4-Thiazolidinones

Abstract

A microwave-enhanced, rapid, three-component one-pot condensation method has been developed for the synthesis of 4-thiazolidinones using environmentally benign solvent ethanol in open vessels at atmospheric pressure. Applying this methodology ten different 4-thiazolidinones were synthesized in good yields.

Key words

microwave - heterocycles - condensation - 4-thiazolidinones - synthesis

References

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8

Typical Procedure for the Synthesis of 4-Thiazolidinones: A mixture of glycine methyl ester hydrochloride (1a, 0.50 g, 4.00 mmol), aldehyde (2e, 1.66 g, 8.30 mmol), mercaptoacetic acid (0.83 mL, 12.00 mmol), diisopropylethylamine (0.85 mL, 4.83 mmol), and molecular sieves (4 Å, 0.10 g) in EtOH (10 mL) was irradiated with microwaves (power: 100 W) at 120 °C for 30 min, following which the sample was cooled using compressed air. The reaction mixture was diluted with CHCl₃ (75 mL), sequentially washed with sat. NaHCO₃, H₂O, brine, dried (Na₂SO₄) and solvent was removed in vacuo to get crude product that was purified by column chromatography (silica gel, hexanes-EtOAc) to afford 4e (1.00 g, 80%). ¹H NMR (300 MHz, CDCl₃): δ = 2.85-2.86 (m, 1 H), 2.92 (s, 6 H), 3.50-3.63 (s, 3 H), 3.83 (br s, 2 H), 4.64 (d, J = 17.1 Hz, 1 H), 6.67 (br s, 0.6 H), 7.07 (br s, 0.7 H), 7.34 (d, J = 9.0 Hz, 1 H), 7.55 (d, J = 3.3 Hz, 2 H), 7.90 (br s, 1 H), 8.31 (m, 1 H). ¹³C NMR (300 MHz, CDCl₃): δ = 31.94, 43.75, 44.53, 51.76, 58.47, 76.72, 112.97, 121.63, 122.69, 124.83, 124.94, 126.18, 131.33, 168.09. MS (ESI): m/z = 345 [M + H].