Ytterbium(III) Triflate Catalyzed One-Pot Synthesis of 1,3-Thiazolidin-2-imines­ from Epichlorohydrin and Thioureas

Abstract

2-Arylimino-3-aryl-1,3-thiazolidines were successfully obtained from epichlorohydrin and thioureas in DMF catalyzed by Yb(OTf)₃. Inversion of the configuration occurred at the chiral center of the epoxide.

ytterbium triflate - cyclization - thiazolidinimine - epi­chlorohydrin - thiourea

References and Notes

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<A NAME="RW20307ST-10">10</A>

HPLC conditions: DAICEL CHIRALCELOD-H-4.6 × 250 mm, hexane-i-PrOH-Et₂NH = 90:10:1 (% v/v/v), 236 nm, 0.8 mL/min, 30 °C.

<A NAME="RW20307ST-11">11</A>

Typical Experimental Procedure for Cyclization of Thioureas with Epoxides
Thiourea 2 (5 mmol) was added to a stirred mixture of DMF (20 mL) and epoxide 1. The reaction was monitored by TLC until completion. The temperature of this reaction was kept at 70 °C (or r.t.) for 72 h, then the solvent was removed by distillation at reduced pressure. The residual was purified on silica gel (PE-EtOAc-CH₂Cl₂ = 10:1:1) to give thiazolindinimes 3 as white crystals.
Spectral data for obtained compounds:
(3-Phenyl-2-(phenylimino)thiazolidin-5-yl)methanol (3a)
White crystalline solid; mp 86.0-88.0 °C. ESI-MS: m/z (%) = 282.9 (70), 163.8 (100), 117.9 (56). Anal. Calcd for C₁₆H₁₆N₂OS: C, 67.58; H, 5.67; N, 9.85; Found: C, 67.50; H, 5.78; N, 9.79. IR (KBr): ν_max = 3274, 1645, 1595, 1529 cm^-1. ¹H NMR (400 MHz, CDCl₃,): δ = 2.13 (dd, 1 H, J ₁ = 5.6 Hz, J ₂ = 1.2 Hz), 2.46 (d, 1 H, J = 6.4 Hz,), 3.20 (m, 1 H), 3.84 (q, 1 H, J = 7.2 Hz), 3.98 (q, 1 H, J = 5.6 Hz), 6.16 (s, 1 H), 6.98-7.53 (m, 10 H). ¹³C NMR (100 MHz, CDCl₃): δ = 24.5, 32.0, 55.2, 119.3 (2 × CH), 123.0, 128.5, 128.7 (2 × CH), 130.4 (4 × CH), 138.4, 141.0, 153.9.
(3-Butyl-2-(phenylimino) thiazolidin-5-yl)methanol (3h)
White crystalline solid; mp: 69.4-71.5 °C. MS (EI): m/z (%) = 265 (4) [M⁺ + 1], 231 (85), 132 (65), 106 (100). Anal. Calcd for C₁₄H₂₀N₂OS: C, 63.60; H, 7.62; N, 10.60. Found: C, 63.51; H, 7.81; N, 10.52. IR (KBr): ν_max = 3355, 2949, 1639, 1510 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 0.87 (t, 3 H, J = 7.2 Hz), 1.24 (m, 2 H), 1.40 (m, 2 H,), 2.07 (d, 1 H, J = 5.2 Hz), 2.41 (d, 1 H, J = 5.6 Hz), 3.16 (m, 3 H), 3.68 (m, 1 H), 3.98 (q, 1 H, J = 5.2 Hz), 4.25 (s, 1 H), 7.26-7.47 (m, 5 H). ¹³C NMR (100 MHz, CDCl₃): δ = 13.5, 19.7, 24.4, 32.0, 32.1, 40.2, 54.9, 127.7 (2 × CH), 128.5, 129.9 (2 × CH), 141.5, 156.6.