Efficient Microwave Enhanced Synthesis of 4-Thiazolidinones

Veeresa Gududuru; Viet Nguyen; James T. Dalton; Duane D. Miller

doi:10.1055/s-2004-832811

LETTER

Efficient Microwave Enhanced Synthesis of 4-Thiazolidinones

Veeresa Gududuru^a, Viet Nguyen^a, James T. Dalton^b, Duane D. Miller*^a
^a Department of Pharmaceutical Sciences, College of Pharmacy, University of Tennessee, Memphis, TN 38163, USA
Fax: +1(901)4483446; e-Mail: dmiller@utmem.edu;
^b Division of Pharmaceutics, College of Pharmacy, The Ohio State University, Columbus, OH 43210, USA

Abstract

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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

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References

1a Newkome GR. Nayak A. Advances in Heterocyclic Chemistry Vol. 25: Academic Press; New York: 1979. p.83

1b Singh SP. Parmar SS. Raman K. Stenberg VI. Chem. Rev. 1981, 81: 175

2 Homes CP. Chinn JP. Look CG. Gordon EM. Gallop MA. J. Org. Chem. 1995, 60: 7328

3 Srivatsava T. Haq W. Katti SB. Tetrahedron 2002, 58: 7619

4 Srivatsava SK. Srivatsava SL. Srivatsava SD. J. Indian Chem. Soc. 2000, 77: 104

5 Sharma RC. Kumar D. J. Indian Chem. Soc. 2000, 77: 492

6 Gedye R. Smith F. Westaway K. Ali H. Baldisera L. Laberge L. Rousell J. Tetrahedron Lett. 1986, 27: 279

7 Khatri BL. Trivedi AM. Sodha VA. Hirpara HM. Parekh HH. Indian J. Heterocycl. Chem. 2002, 12: 175

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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].