Novel Method for the Synthesis of Substituted Imidazothiazolones

Abstract

A general and highly selective method for the synthesis of 4-substituted 3a,6a-diphenyltetrahydro-2H-imidazo[4,5-d][1,3]thiazole-2,5(3H)-diones has been developed through a new reaction of 1-substituted 5-hydroxy-4,5-diphenyl-1Н-imidazol-2(5Н)-оnes with potassium thiocyanate in the presence of acetic acid in acetonitrile. Details of supramolecular organization in the crystalline imidazothiazolones, as revealed by X-ray diffraction, are highlighted.

Key words

cyclocondensations - potassium thiocyanate - heterocycles - polycycles - imidazolоnes - imidazothiazoles

• References and Notes

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• 12 1-Substituted 5-Hydroxy-4,5-diphenyl-1,5-dihydro-2H-imidazol-2-ones 8a–h; General Procedure 63% aq HNO₃ (5 mL) was added dropwise to a suspension of the appropriate imidazolone 9a–h (4 mmol) in MeCN (25 mL). The reaction was monitored by the dissolution of the precipitated 9a–h and by the change in color of the solution. The mixture was then extracted with 1:1 CHCl₃/H₂O, the CHCl₃ layer was evaporated, and the product was washed with Et₂O. 5-Hydroxy-1-methyl-4,5-diphenyl-1,5-dihydro-2H-imidazol-2-one (8a) White powder; yield: 0.94 g (88%); mp 222–224 °С. ¹H NMR (300 MHz, DMSO-d ₆): δ = 2.55 (s, 3 H, Me), 7.25–7.48 (m, 7 H, Ph), 7.52–7.56 (m, 1 H, Ph), 7.75 (s, 1 H, OH), 8.01–8.04 (m, 2 H, Ph). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 23.82 (Me), 92.61 [С(Ph)OH], 125.18, 128.75, 128.83, 129.05, 129.60, 133.35, 136.61 (Ph), 163.44 (C=O), 186.39 (C=N). MS: m/z (%) = 266 (6) [M⁺], 250 (61), 180 (13), 163 (56), 135 (53), 134 (56), 118 (100). Anal. Calcd for C₁₆H₁₄N₂O₂: C, 72.16; H, 5.30; N, 10.52. Found: C, 72.07; H, 5.34; N 10.47. 1-Ethyl-5-hydroxy-4,5-diphenyl-1,5-dihydro-2H-imidazol-2-one (8b) White powder; yield: 0.91 g (81%); mp 214–216 °С. ¹H NMR (300 MHz, DMSO-d ₆): δ = 0.88 (t, J = 7.1 Hz, 3 H, Me), 2.87–3.04 (m, 1 H, СH₂), 3.13–3.30 (m, 1 H, CH₂), 7.25–7.50 (m, 7 H, Ph), 7.53–7.57 (m, 1 H, Ph), 7.73 (s, 1 H, OH), 7.99–8.02 (m, 2 H, Ph). ¹³C NMR (50 MHz, DMSO-d ₆): δ = 13.79 (Me), 33.58 (CH₂), 92.81 [С(Ph)OH], 125.20, 128.75, 128.82, 128.97, 129.65, 133.32, 137.32 (Ph), 163.38 (C=O), 186.07 (C=N). MS: m/z (%) = 280 (13) [M⁺], 252 (3), 208 (4), 177 (50), 165 (8), 148 (75), 134 (35), 105 (75), 91 (7), 77 (100). Anal. Calcd for C₁₇H₁₆N₂O₂: C, 72.84; H, 5.75; N, 9.99. Found: C, 72.79; H, 5.78; N, 10.06. 4-Substituted 3a,6a-Diphenyltetrahydro-2H-imidazo[4,5-d][1,3]thiazole-2,5(3H)-diones 13a–h; General Procedure AcOH (3.00 mL) was added to a solution of the appropriate imidazolone 8a–h (4 mmol) and KSCN (0.44 g, 4.5 mmol) in MeCN (17 mL) at r.t., and the mixture was refluxed for 1 h. The mixture was allowed to cool to r.t. and kept for 24 h to give a precipitate. (3aR*,6aR*)-4-Methyl-3a,6a-diphenyltetrahydro-2H-imidazo[4,5-d][1,3]thiazole-2,5(3H)-dione (13a) White powder; yield: 1.20 g (92%); mp >300 °С. ¹H NMR (300 MHz, DMSO-d ₆): δ = 2.64 (s, 3 H, Me), 6.85–6.98 (m, 2 H, Ph), 7.01–7.17 (m, 6 H, Ph), 7.18–7.28 (m, 2 H, Ph), 8.35 [s, 1 H, NH(NCO)], 9.72 [s, 1 H, NH(SCO)]. ¹³C NMR (75 MHz, DMSO-d ₆): δ = 25.73 (Me), 83.19, 87.52 [(Ph)–C–C–(Ph)], 126.93, 127.49, 127.57, 128.07, 128.18, 128.71 (Ph), 132.92, 137.51 [C(Ph)], 158.38 [(N)C=O], 171.91 [(S)C=O]. HRMS: m/z [M + H]⁺ calcd for C₁₇H₁₆N₃O₂S: 326.0958; found: 326.0958. (3aR*,6aR*)-4-Ethyl-3a,6a-diphenyltetrahydro-2H-imidazo[4,5-d][1,3]thiazole-2,5(3H)-dione (13b) White powder; yield: 1.22 g (74%); mp 235–237 °С. ¹H NMR (300 MHz, DMSO-d ₆): δ = 1.12 (t, J = 7.0 Hz, 3 H, Me), 2.71–2.91 (m, 1 H, CH₂), 3.31–3.50 (m, 1 H, CH₂), 6.90–7.01 (m, 2 H, Ph), 7.02–7.19 (m, 6 H, Ph), 7.20–7.31 (m, 2 H, Ph), 8.20 [s, 1 H, NH(NCO)], 9.65 [s, 1 H, NH(SCO)]. ¹³C NMR (75 MHz, DMSO-d ₆): δ = 14.80 (Me), 35.15 (CH₂), 83.81, 87.80 [(Ph)–C–C–(Ph)], 126.95, 127.47, 127.51, 127.84, 128.14, 128.65 (Ph), 133.87, 137.49 [C(Ph)], 158.42 [(N)C=O], 172.27 [(S)C=O]. HRMS: m/z [M + H]⁺ calcd for C₁₈H₁₈N₃O₂S: 340.1114; found: 340.1110.