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Synlett 2013; 24(20): 2705-2708
DOI: 10.1055/s-0033-1340283
DOI: 10.1055/s-0033-1340283
letter
Microwave-Assisted Copper-Powder-Catalyzed Synthesis of Pyrimidinones from β-Bromo α,β-Unsaturated Carboxylic Acids and Amidines
Authors
Further Information
Publication History
Received: 30 August 2013
Accepted after revision: 05 September 2013
Publication Date:
05 November 2013 (online)
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.
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References and Notes
- 1 Driscoll JS, Marquez VE, Plowman J, Liu PS, Kelley JA, Barchi JJ. Jr. J. Med. Chem. 1991; 34: 3280
- 2 Salimbeni A, Canevotti R, Paleari F, Poma D, Caliari S, Fici F, Cirillo R, Renzetti AR, Subissi A, Belvisi L, Bravi G, Scolastico C, Giachetti A. J. Med. Chem. 1995; 38: 4806
- 3 Saladino R, Crestini C, Palamara AT, Danti MC, Manetti F, Corelli F, Garaci E, Botta M. J. Med. Chem. 2001; 44: 4554
- 4 Madhavan GR, Chakrabarti R, Vikramadithyan RK, Mamidi RN. V. S, Balraju V, Rajesh BM, Misra P, Kumar SK. B, Lohray BB, Lohray VB, Rajagopalan R. Bioorg. Med. Chem. 2002; 10: 2671
- 5 Saleh MA, Abdel-Megeed MF, Abdo MA, Shokr AM. Molecules 2003; 8: 363
- 6 Petricci E, Mugnaini C, Radi M, Togninelli A, Bernardini C, Manetti F, Parlato MC, Renzulli ML, Alongi M, Falciani C, Corelli F, Botta M. ARKIVOC 2006; (vii): 452
- 7 Mai A, Artico M, Rotili D, Tarantino D, Clotet-Codina I, Armand-Ugón M, Ragno R, Simeoni S, Sbardella G, Nawrozkij MB, Samuele A, Maga G, Esté JA. J. Med. Chem. 2007; 50: 5412
- 8 Guo Q, Yang H, Liu H, Jiang Y, Fu H. Synlett 2010; 2611
- 9 Yu L, Wang M, Li P, Wang L. Appl. Organomet. Chem. 2012; 26: 576
- 10a Liu X, Fu H, Jiang Y, Zhao Y. Angew. Chem. Int. Ed. 2009; 48: 348
- 10b Zhang X, Ye D, Sun H, Guo D, Wang J, Huang H, Zhang X, Jiang H, Liu H. Green Chem. 2009; 11: 1881
- 11 It has also been reported that quinazolinones can be synthesized by CuI-catalyzed coupling of 2-iodobenzamides with methanimidamide acetate followed by condensative cyclization; see: Zhou J, Fu L, Lv M, Liu J, Pei D, Ding K. Synthesis 2008; 3974
- 12a Cho CS, Patel DB, Shim SC. Tetrahedron 2005; 61: 9490
- 12b Cho CS, Shim HS. Tetrahedron Lett. 2006; 47: 3835
- 12c Cho CS, Patel DB. Tetrahedron 2006; 62: 6388
- 12d Cho CS, Kim JU, Choi H.-J. J. Organomet. Chem. 2008; 693: 3677
- 12e Cho CS, Kim HB, Lee SY. J. Organomet. Chem. 2010; 695: 1744
- 12f Cho CS, Kim HB. Catal. Lett. 2010; 140: 116
- 12g Cho CS, Kim HB. J. Organomet. Chem. 2011; 696: 3264
- 12h Lee HK, Cho CS. Appl. Organomet. Chem. 2012; 26: 185
- 12i Lee HK, Cho CS. Appl. Organomet. Chem. 2012; 26: 406
- 12j Cho CS, Son JI, Yoon NS. Appl. Organomet. Chem. 2012; 26: 499
- 12k Lee HK, Cho CS. Appl. Organomet. Chem. 2012; 26: 570
- 12l Ho SL, Cho CS, Choi H.-J, Sohn H.-S. Appl. Organomet. Chem. 2013; 27: 277
- 12m Son J.-K, Cho CS, Choi H.-J. Appl. Organomet. Chem. 2013; 27: 380
- 12n Bae YK, Cho CS. Synlett 2013; 24: 1848
- 13a Arnold Z, Holly A. Collect. Czech. Chem. Commun. 1961; 26: 3059
- 13b Coates RM, Senter PD, Baker WR. J. Org. Chem. 1982; 47: 3597
- 14a Brahma S, Ray JK. Tetrahedron 2008; 64: 2883
- 14b Jana R, Chatterjee I, Samanta S, Ray JK. Org. Lett. 2008; 10: 4795
- 14c Karthikeyan P, Meena Rani A, Saiganesh R, Balasubramanian KK, Kabilan S. Tetrahedron 2009; 65: 811
- 14d Samanta S, Jana R, Ray JK. Tetrahedron Lett. 2009; 50: 6751
- 14e Nandi S, Ray JK. Tetrahedron Lett. 2009; 50: 6993
- 14f Jana R, Paul S, Biswas A, Ray JK. Tetrahedron Lett. 2010; 51: 273
- 14g Samanta S, Yasmin N, Kundu D, Ray JK. Tetrahedron Lett. 2010; 51: 4132
- 14h Yasmin N, Ray JK. Synlett 2010; 924
- 14i Paul S, Gorai T, Koley A, Ray JK. Tetrahedron Lett. 2011; 52: 4051
- 15 Dalcanale E, Montanari F. J. Org. Chem. 1986; 51: 567
- 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.