An Efficient One-Pot Multicomponent Synthesis of 2,3-Dihydro-3-alkyl/aryl-2-thioxoquinazolin-4(1H)-ones under Solvent-Free Conditions

Abstract

A series of 2,3-dihydro-3-alkyl/aryl-2-thioxoquinazolin-4(1H)-one is prepared by one-pot multicomponent reaction of anthranilic acid, S,S-dimethyl trithiocarbonate and aliphatic/aromatic amine under solvent-free conditions.

Key words

dihydroquinazoline - multicomponent reaction - solvent-free - trithiocarbonate - anthranilic acid

• References and Notes

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• 16 General Procedure for the Synthesis of 2,3-Dihydro-3-alkyl-2-thioxoquinazolin-4(1H)-diones 4a–f: Anthranilic acid (1; 2.5 mmol), amine 2a–f (2.5 mmol) and dimethyl trithiocarbonate (3; 2.5 mmol) were heated at 90–100 °C with stirring for 1 h. Then H₂O was added, and the product was extracted with EtOAc. After the organic layer was dried over anhyd Na₂SO₄, filtered and evaporated. The residue was recrystallized from EtOAc and hexane to afford pure products 4a–f. In cases where further purification was required, the crude products were subjected to column chromatography (10% EtOAc–hexane as eluent) to give the pure product. Compound 4a: colorless crystals; mp 270–271 °C. IR (KBr): 1610, 1685, 3178 cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.85 (s, 3 H), 7.15 (d, J = 6.0 Hz, 1 H), 7.32 (t, J = 11.4 Hz, 1 H), 7.65 (t, J = 12.3 Hz, 1 H), 8.15 (d, J = 6.0 Hz, 1 H), 10.32 (s, 1 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 33.3, 115.3, 115.6, 124.4, 127.3, 135.3, 139.1, 159.6, 175.4. MS: m/z = 192 [M⁺]. Anal. Calcd for C₉H₈N₂OS: C, 56.23; H, 4.19; N, 14.57. Found: C, 56.21; H, 4.20; N, 14.59.
• 17 General Procedure for the Synthesis of 2,3-Dihydro-3-aryl-2-thioxoquinazolin-4(1H)-ones 4g–j: Anthranilic acid (2.5 mmol), aromatic amine (2.5 mmol), and dimethyl trithiocarbonate (2.5 mmol) were heated at 130 °C in the presence of SnCl₂⋅2H₂O (5 mol%) with stirring for 1 h. Then H₂O was added, and the product was extracted with EtOAc. After the organic layer was dried over anhyd Na₂SO₄, filtered and evaporated. The residue was recrystallized from EtOAc and hexane to afford products 4g–j. In cases where further purification was required, the crude products were subjected to column chromatography (10% EtOAc–hexane as eluent) to give the pure product. Compound 4g: white solid; mp 296 °C (Lit.^18b 295 °C). IR (KBr): 1661 (C=O), 3245 (NH), 1227 (C=S) cm^–1. ¹H NMR (400 MHz, DMSO-d ₆): δ = 6.50–7.90 (m, 9 H, ArH), 11.60 (br s, 1 H, NH exchange with D₂O). ¹³C NMR (75.5 MHz, DMSO-d ₆): δ = 115.3, 115.5, 124.1, 124.4, 126.6, 127.8, 128.2, 132.5, 132.7, 139.1, 159.7, 175.5. MS: m/z = 252 [M⁺]. Anal. Calcd for C₁₄H₁₀N₂OS: C, 66.12; H, 3.96; N, 11.02. Found: C, 66.13; H, 3.99; N, 11.05.
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• 19 Benzylamine (2e; 2.5 mmol) and dimethyl trithiocarbonate (3; 2.5 mmol) were heated at 90–100 °C with stirring for 1 h. Then H₂O was added, and the product was extracted with EtOAc. After the organic layer was dried over anhyd Na₂SO₄, filtered and evaporated. The residue was subjected to silica gel column chromatography (5% EtOAc–hexane as eluent) to give intermediate A. Intermediate A: ¹H NMR (400 MHz, CDCl₃): δ = 1.58 (s, 1 H), 2.63 (s, 3 H), 4.86 (d, J = 16.0 Hz, 2 H), 7.30–7.36 (m, 5 H). ¹³C NMR (75.5 MHz, CDCl₃): δ = 18.1, 51.1, 127.7, 127.9, 128.7, 136.1, 199.0.
• 20 Crystallographic data for the X-ray crystal structure analysis reported in this paper have been deposited with the Cambridge Crystallographic Data Center (CCDC) as supplementary publication no. CCDC 879350. Copies of the data can be obtained free of charge on application to the Director, CCDC, 12 Union Road, Cambridge CB2 1EZ, UK [fax: [phone], e-mail: [e-mail]].