A New Synthesis Strategy for Rhodanine and Its Derivatives

Abstract

Rhodanine and its derivatives have been known as privileged structures in pharmacological research because of their wide spectrum of biological activities, but the synthesis method of rhodanine skeleton is limited. In this paper, not only rhodanine skeleton, but also N-aryl rhodanines can be directly prepared via the reaction of thioureas and thioglycolic acid in one step catalyzed by protic acid, which provides a new approach of the synthesis of rhodanine and its derivatives. The developed strategy is straightforward, efficient, atom economical, and convenient in good yields.

Key words

rhodanine - thiourea - thioglycolic acid - thiazolidone - heterocycle

Publication History

Received: 17 March 2021

Accepted after revision: 19 April 2021

Accepted Manuscript online:
19 April 2021

Article published online:
10 May 2021

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• 56 General Experimental Procedures To a solution of thiourea (10 mmol) and thioglycolic acid (10 mmol) in toluene (20 mL) was added hydrochloric acid (12 mmol). The reaction mixture was heated to 110 °C under stirring monitored by TLC. The mixture was then quenched by the addition of H₂O and extracted with toluene. The isolated organic phase was dried over Na₂SO₄, filtered, concentrated in vacuo, and purified by column chromatography on silica gel eluting with ethyl acetate–hexane.
• 57 Characterization Data
  2-Thioxothiazolidin-4-one Light yellow solid, mp 169–170 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 13.15 (s, 1 H), 4.27 (s, 2 H). 3-Methyl-2-thioxothiazolidin-4-one Light yellow solid, mp 69–70 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 4.25 (s, 2 H), 3.32–3.23 (s, 3 H). 3-Phenyl-2-thioxothiazolidin-4-one Light yellow solid, mp 188–190 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 7.55–7.46 (m, 3 H), 7.28–7.26 (d, 2 H), 4.39 (s, 2 H). 3-(4-Methylphenyl)-2-thioxothiazolidin-4-one Light yellow solid, mp 169–170 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 7.33–7.31 (d, 2 H), 7.14–7.12 (d, 2 H), 4.38 (s, 2 H), 2.50–2.25 (s, 3 H). 3-[3-(Trifluoromethyl)phenyl]-2-thioxothiazolidin-4-one Yellow solid, mp 176–177 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 7.89–7.87 (d, 1 H), 7.81–7.78 (m, 2 H), 7.67–7.61 (m, 1 H), 4.38 (s, 2 H). 3-(2-Chlorophenyl)-2-thioxothiazolidin-4-one Yellow solid, mp 122–123 ℃. ¹H NMR (DMSO-d ₆, 400 MHz): δ = 7.69–7.66 (m, 1 H), 7.58–7.50 (m, 2 H), 7.49–7.45 (m, 1 H), 4.65–4.44 (dd, 2 H). 5-Methyl-3-phenyl-2-thioxothiazolidin-4-one Light yellow solid, mp 118–119 ℃. ¹H NMR (CDCl₃, 400 MHz): δ = 7.55–7.47 (m, 3 H), 7.21–7.19 (m, 2 H), 4.43–4.37 (q, 1 H), 1.80–1.78 (d, 3 H). 5-Methyl-3-(2-chlorophenyl)-2-thioxothiazolidin-4-one Light yellow sticky oil. ¹H NMR (CDCl₃, 400 MHz): δ = 7.58–7.56 (m, 1 H), 7.47–7.45 (m, 2 H), 7.26–7.25 (m, 1 H), 4.52–4.40 (m, 1 H), 1.85–1.80 (m, 3 H). 3,5-Diphenyl-2-thioxothiazolidin-4-one Light yellow solid, mp 132–133 ℃. ¹H NMR (CDCl₃, 400 MHz): δ = 7.58–7.57 (m, 3 H), 7.45–7.43 (m, 4 H), 7.36–7.34 (m, 3 H), 5.89 (s, 1 H). 5-Phenyl-3-[3-(trifluoromethyl)phenyl]-2-thioxothiazolidin-4-one Light yellow sticky. ¹H NMR (CDCl₃, 400 MHz): δ = 8.04–8.02 (t, 1 H), 7.45–7.41 (m, 4 H), 7.36–7.27 (m, 4 H), 5.90 (s, 1 H)