Synlett, Table of Contents Synlett 2012; 23(14): 2111-2115DOI: 10.1055/s-0032-1316698 letter © Georg Thieme Verlag Stuttgart · New YorkAn Efficient One-Pot Multicomponent Synthesis of 2,3-Dihydro-3-alkyl/aryl-2-thioxoquinazolin-4(1H)-ones under Solvent-Free Conditions Nepram Sushuma Devi Department of Chemistry, Manipur University, Canchipur 795003, Manipur, India, Fax: +91(385)2435145 Email: ok_mukherjee@yahoo.co.in , Sarangthem Joychandra Singh Department of Chemistry, Manipur University, Canchipur 795003, Manipur, India, Fax: +91(385)2435145 Email: ok_mukherjee@yahoo.co.in , Okram Mukherjee Singh* Department of Chemistry, Manipur University, Canchipur 795003, Manipur, India, Fax: +91(385)2435145 Email: ok_mukherjee@yahoo.co.in› Author AffiliationsRecommend Article Abstract Buy Article All articles of this category 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 Key wordsdihydroquinazoline - multicomponent reaction - solvent-free - trithiocarbonate - anthranilic acid Full Text References References and Notes 1a Russel HE, Alaimo RJ. J. Med. Chem. 1972; 15: 335 1b Hour M.-J, Huang L.-J, Kuo S.-C, Xia Y, Bastow K, Nakanishi Y, Hamel E, Lee K.-H. J. Med. Chem. 2000; 43: 4479 1c Neil GL, Li LH, Buskirk HH, Moxley TE. Cancer Chemother. Rep. 1972; 56: 163 1d Xu Z, Zhang Y, Fu H, Zhong H, Hong K, Zhu W. Bioorg. Med. Chem. Lett. 2011; 21: 4005 1e Somers F, Ouedraogo R, Antoine M.-H, de Tullio P, Becker B, Fontaine J, Damas J, Dupont L, Rigo B, Delarge J, Lebrun P, Pirotte B. J. Med. Chem. 2001; 44: 2575 2a Rhim H, Lee YS, Park SJ, Chung BY, Leed JY. Bioorg. Med. Chem. Lett. 2005; 15: 283 2b Heo JH, Seo HN, Choe YJ, Kim S, Oh CH, Kim YD, Rhim H, Choo DJ, Kim J, Lee JY. Bioorg. Med. Chem. Lett. 2008; 18: 3899 3 Hess HJ, Cronin TH, Scriabine A. J. Med. 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Green Chem. 2011; 13: 718 11b Portela-Cubilo F, Scott JS, Walton JC. J. Org. Chem. 2009; 74: 4934 12 Chen J, Su W, Wu H, Liub M, Jina C. Green Chem. 2007; 9: 972 13 Bouillon I, Krchnak V. J. Comb. Chem. 2007; 9: 912 14 Albrecht U, Reinke H, Langer P. Synthesis 2006; 3067 15a Singh OM, Devi NS. J. Org. Chem. 2009; 74: 3141 15b Singh OM, Devi NS, Thokchom DS, Sharma GJ. Eur. J. Med. Chem. 2010; 45: 2250 15c Singh OM, Devi NS, Devi LR, Lim KB, Yoon YJ, Lee S.-G. Bull. Korean Chem. Soc. 2011; 32: 175 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. 18a Wang F, Zhao P, Xi C. Tetrahedron Lett. 2011; 52: 231 18b Allameh S, Heravi MM, Hashemi MM, Bamoharram FF. Chin. Chem. Lett. 2011; 22: 131 18c Tiwari VK, Kale RR, Mishra BB, Singh A. ARKIVOC 2008; (xiv): 27 18d Lecoutey C, Fossey C, Rault S, Fabis F. Eur. J. Org. Chem. 2011; 2785 18e Reddy CK, Reddy PS. N, Ratnam CV. Indian J. Chem., Sect. B: Org. Chem. Incl. Med. Chem. 1987; 9: 882 18f Lakhan R, Srivastava M. J. Chem. Sci. 1993; 1: 11 18g Adib M, Sheikhi E, Bijanzadehb HR. Synlett 2012; 23: 85 18h Azizian J, Mohamadi AA, Karimi AR. Synth. Commun. 2003; 3: 415 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: +44(1223)336033, e-mail: deposit@ccdc.cam.ac.uk].
