Direct Synthesis of 1-Alkyl-6-hydroxyalkyl-3a,6a-diphenylglycolurils from 1-Alkylimidazolinones and Their Cyclic Analogues

Abstract

Two methods for the direct synthesis of previously inaccessible 1-alkyl-6-(hydroxyalkyl)-3a,6a-diphenylglycolurils have been developed as a result of a study of novel cyclocondensations of 1-alkylureas with tetrahydroimidazooxazolones, tetrahydroimidazooxazinones and 1-(hydroxyalkyl)ureas with 1-substituted imidazolinones. A mechanism to rationalize the highly regioselective formation of the target glycolurils is proposed.

Key words

glycolurils - imidazolinones - condensation

• References and Notes

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• 8 Synthesis of 1-Alkyl-6-hydroxyalkyl-3a,6a-diphenylglycolurils 3 Method 1: To a mixture of the corresponding urea 8b–d (1 mmol), bicyclic compounds 4 or 5 (1 mmol) and MeCN (10 mL) for 4 or MeOH (10 mL) for 5, the hydrochloric acid (0.1 mL, 36.5%) was added. The reaction mixture was heated at reflux with stirring for 20 min (for 4) or 8 h (for 5). The reaction mixture was then cooled and the precipitate was filtered off and washed with a mixture of CHCl₃/H₂O (1:1, 4 mL), and dried in air. Method 2: To a solution of the corresponding urea 9a and 9b (1 mmol) and imidazolinone 10a–d (1 mmol) in MeCN (10 mL), the hydrochloric acid (0.1 mL, 36.5%) was added. The reaction mixture was heated at reflux with stirring for 20 min. The reaction mixture was then cooled and the precipitate was filtered off and washed with a mixture of CHCl₃/H₂O (1:1, 4 mL), and dried in air.
• 9 Analytical Data for 1-Ethyl-6-(2-hydroxyethyl)-3a,6a-diphenyltetrahydroimidazo[4,5-d]imidazole-2,5(1H,3H)-dione (3a): Yield: 88% (Method 1), 76% (Method 2); white solid; mp 275–277 °C. ¹H NMR (300 MHz, DMSO-d ₆): δ = 1.21 (t, J = 6.8 Hz, 3 H, Me), 2.91–3.10 (m, 2 Н, CH₂), 3.11–3.30 (m, 2 Н, CH₂), 3.56–3.73 (m, 2 H, CH₂), 4.79 (t, J = 5.5 Hz, 1 H, OH), 6.75–6.89 (m, 2 H, Ph), 6.92–7.01 (m, 2 Н, Ph), 7.02–7.14 (m, 6 Н, Ph), 8.02 (s, 1 H, NH), 8.12 (s, 1 H, NH). ¹³C NMR (75 MHz, DMSO-d ₆): δ = 14.84 (Me), 36.95, 44.68, 59.46 (CH₂), 79.28, 89.91 ((Ph)-C-C-(Ph)), 127.11, 127.41, 127.86, 128.04, 128.42 (Ph), 133.73, 137.45 (C(Ph)), 159.87, 160.30 (C=O). HRMS (ESI): m/z [M+Na]⁺ calcd for C₂₀H₂₂N₄O₃Na⁺: 389.1584; found: 389.1580.