Microwave-Assisted Copper-Powder-Catalyzed Synthesis of Pyrimidinones from β-Bromo α,β-Unsaturated Carboxylic Acids and Amidines

Son Long Ho; Chan Sik Cho

doi:10.1055/s-0033-1340283

Synlett, Inhaltsverzeichnis

Synlett 2013; 24(20): 2705-2708
DOI: 10.1055/s-0033-1340283

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Microwave-Assisted Copper-Powder-Catalyzed Synthesis of Pyrimidinones from β-Bromo α,β-Unsaturated Carboxylic Acids and Amidines

Son Long Ho

Department of Applied Chemistry, Kyungpook National University, Daegu 702-701, South Korea Fax: +82(53)9506594 eMail: cscho@knu.ac.kr

,

Chan Sik Cho*

Department of Applied Chemistry, Kyungpook National University, Daegu 702-701, South Korea Fax: +82(53)9506594 eMail: cscho@knu.ac.kr

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Abstract

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Abstract

β-Bromo α,β-unsaturated carboxylic acids were coupled and cyclized with amidine hydrochlorides by microwave irradiation in the presence of catalytic amounts of copper powder and a base to give the corresponding pyrimidinones in high yields.

Key words

copper - coupling - cyclization - heterocycles - heterogeneous catalysis

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Referenzen

References and Notes
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16 The reaction appears to proceed by an initial Cu-catalyzed C–N coupling between 1a and 2a followed by condensative cyclization.
17 The reaction did not proceed efficiently under normal heating (100 °C, 3 h), 3a being obtained in only 14% yield.
18 Pyrimidinones 3; General Procedure A 10 mL microwave reaction tube was charged with the appropriate β-bromo α,β-unsaturated carboxylic acid 1 (0.5 mmol) and amidine hydrochloride 2 (1 mmol), together with Cu powder (0.05 mmol), t-BuONa (2 mmol), and DMF (3 mL). The mixture was heated to 100 °C for 30 min by microwave irradiation (CEM Discover Microwave System) at 100 W initial power. The mixture was then cooled to r.t. and filtered through a short column of silica gel (CHCl₃–MeOH) to remove inorganic salts. Evaporation of the solvent gave a crude mixture that was purified by TLC [silica gel 60 GF₂₅₄ (Merck), CHCl₃–MeOH]. 6-Methyl-2-phenyl-5,6,7,8-tetrahydroquinazolin-4(3H)-one (3c) White solid; yield: 103 mg (86%); mp 254–256 °C. IR (KBr): 1638 (C=O) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.12 (d, J = 6.6 Hz, 3 H), 1.41–1.51 (m, 1 H), 1.83–1.95 (m, 2 H), 2.05–2.12 (m, 1 H), 2.71–2.84 (m, 3 H), 7.44–7.54 (m, 3 H), 8.19–8.21 (m, 2 H), 12.88 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 21.73, 28.25, 30.31, 30.63, 32.03, 119.91, 127.66, 129.02, 131.58, 132.65, 153.45, 162.47, 164.95. HRMS (EI): m/z [M⁺] calcd for C₁₅H₁₆N₂O: 240.1263; found: 240.1260. Anal. Calcd for C₁₅H₁₆N₂O: C, 74.97; H, 6.71; N, 11.66. Found: C, 74.70; H, 6.72; N, 11.83. 2,6-Diphenyl-5,6,7,8-tetrahydroquinazolin-4(3H)-one (3d) White solid; yield: 125 mg (83%); mp 223–225 °C. IR (KBr): 1629 (C=O) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.94–2.05 (m, 1 H), 2.18–2.22 (m, 1 H), 2.59–2.66 (m, 1 H), 2.89–3.10 (m, 4 H), 7.24–7.38 (m, 5 H), 7.45–7.52 (m, 3 H), 8.13–8.16 (m, 2 H), 12.18 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 29.79, 32.55, 39.55, 120.02, 126.63, 127.10, 127.46, 128.77, 129.21, 131.81, 132.53, 145.74, 153.55, 162.19, 164.36. HRMS (EI): m/z [M⁺] calcd for C₂₀H₁₈N₂O: 302.1419; found: 302.1416. Anal. Calcd for C₂₀H₁₈N₂O: C, 79.44; H, 6.00; N, 9.26. Found: C, 79.12; H, 5.82; N, 9.20. 2-Phenyl-3,5,6,7-tetrahydro-4H-cyclopenta[d]pyrimidin-4-one (3e)White solid; yield: 80 mg (75%); mp 212–214 °C. IR (KBr): 1650 (C=O) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 2.10–2.18 (m, 2 H), 2.87–3.00 (m, 3 H), 7.44–7.57 (m, 3 H), 8.10–8.12 (m, 2 H), 11.92 (br s, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 20.71, 27.06, 34.33, 127.45, 127.62, 128.19, 128.60, 131.32, 156.73, 161.07, 167.88. HRMS (EI): m/z [M⁺] calcd for C₁₃H₁₂N₂O: 212.0950; found: 212.0952. Anal. Calcd for C₁₃H₁₂N₂O: C, 73.56; H, 5.70; N, 13.20. Found: C, 73.45; H, 5.65; N, 13.11. 2-Phenyl-5,6,7,8,9,10,11,12,13,14-decahydrocyclododeca[d]pyrimidin-4(3H)-one (3h)White solid; yield: 95 mg (61%); mp 223–224 °C. IR (KBr): 1622 (C=O) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 1.25–1.53 (m, 12 H), 1.80–1.92 (m, 4 H), 2.68–2.70 (m, 4 H), 7.44–7.54 (m, 3 H), 8.16–8.18 (m, 2 H), 12.01 (br s, 1 H). ¹³C NMR (100 MHz, CDCl₃): δ = 22.02, 22.87, 23.16, 23.88, 25.25, 25.47, 25.86, 25.99, 28.93, 31.13, 123.11, 127.21, 128.74, 131.38, 132.47, 153.69, 164.61, 165.18. HRMS (EI): m/z [M⁺] calcd for C₂₀H₂₆N₂O: 310.2045; found: 310.2045. Anal. Calcd for C₂₀H₂₆N₂O: C, 77.38; H, 8.44; N, 9.02. Found: C, 77.19; H, 8.48; N, 9.02. 2-Phenyl-5,6-dihydrobenzo[h]quinazolin-4(3H)-one (3i)White solid; yield: 89 mg (65%); mp 229–230 °C. IR (KBr): 1638 (C=O) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 2.98–3.00 (m, 4 H), 7.26–7.29 (m, 1 H), 7.36–7.41 (m, 2 H), 7.55–7.59 (m, 3 H), 8.32–8.41 (m, 3 H), 12.20 (br s, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 26.91, 28.98, 125.73, 126.84, 127.28, 127.84, 128.82, 130.53, 131.62, 132.40, 132.58, 138.71, 155.94, 157.06, 164.10. HRMS (EI): m/z [M⁺] calcd for C₁₈H₁₄N₂O: 274.1106; found: 274.1108. Anal. Calcd for C₁₈H₁₄N₂O: C, 78.81; H, 5.14; N, 10.21. Found: C, 78.72; H, 5.01; N, 10.02. 3-Phenyl-5,6-dihydrobenzo[f]quinazolin-1(2H)-one (3j)White solid; yield: 80 mg (58%); mp 226–228 °C. IR (KBr): 1625 (C=O) cm^–1. ¹H NMR (400 MHz, CDCl₃): δ = 3.01 (s, 4 H), 7.26–7.30 (m, 1 H), 7.33–7.37 (m, 1 H), 7.56–7.63 (m, 4 H), 8.32–8.34 (m, 2 H), 8.79 (d, J = 7.6 Hz, 1 H), 12.63 (br s, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 27.85, 31.30, 126.58, 126.80, 127.04, 127.41, 127.52, 127.83, 128.58, 129.06, 130.24, 132.02, 135.84, 154.97, 161.96, 164.49. HRMS (EI): m/z [M⁺] calcd for C₁₈H₁₄N₂O: 274.1106; found: 274.1104. Anal. Calcd for C₁₈H₁₄N₂O: C, 78.81; H, 5.14; N, 10.21. Found: C, 78.61; H, 5.47; N, 10.31.