Synlett 2016; 27(12): 1836-1839
DOI: 10.1055/s-0035-1561611
letter
© Georg Thieme Verlag Stuttgart · New York

A Green, One-Pot Synthesis of Substituted 2,3-Dihydroquinazoline-4(1H)-ones in the Presence of N-Sulfonic Acid Pyridinium Chloride

Seyedeh Bahareh Azimi
Department of Chemistry, Science and Research Branch, Islamic Azad University, P. O. Box 19395-1775, Tehran, Iran   Email: j.azizian13@gmail.com
,
Javad Azizian*
Department of Chemistry, Science and Research Branch, Islamic Azad University, P. O. Box 19395-1775, Tehran, Iran   Email: j.azizian13@gmail.com
› Author Affiliations
Further Information

Publication History

Received: 08 February 2016

Accepted after revision: 18 March 2016

Publication Date:
13 April 2016 (online)


Abstract

We present a one-pot method for the synthesis of 2,3-dihydroquinazoline-4(1H)-ones. The three-component reaction between isatoic anhydride, primary amines, and dialkyl acetylenedicarboxylates in the presence of N-sulfonic acid pyridinium chloride under solvent-free conditions affords the corresponding alkyl 2-[(alkoxycarbonyl)methyl]-1,2,3,4-tetrahydro-3-alkyl-4-oxo-quinazoline-2-carboxylates in excellent yields.

 
  • References and Notes

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  • 23 Typical Procedure for the Preparation of Compound 5a A mixture of isatoic anhydride (0.163 g, 1 mmol) and aniline (0.093 g, 1 mmol) was stirred under solvent-free conditions at 70 °C for 40 min. After nearly complete conversion into anthranilamide, as indicated by TLC monitoring, dimethyl acetylenedicarboxylate (0.142 g, 1 mmol) was added over 3 min and stirring was continued under same reaction conditions for 20 min. Next, the reaction mixture was cooled to room temperature, H2O (2 mL) was added, and the mixture was allowed to stir for 30 min. The pale yellow precipitate was filtered and and recrystallized from of H2O–EtOH (1:1) to give 5a as pale yellow crystals. Dimethyl 2-[2-(Phenylcarbamoyl)phenylamino]but-2-enedioate (5a) Pale yellow powder, mp 149 °C, yield 0.337 g (95%). IR (KBr): 3312 and 3260 (NH), 1746, 1641 and 1615 (C=O), 1503, 1488, 1434, 1382, 1327, 1248, 1201, 1164, 1129, 1064, 1028, 994, 866, 765, 702, 665, 564 cm–1. 1H NMR (500.13 MHz, acetone-d 6): δ = 3.71 and 3.72 (2 s, 6 H, 2 OCH3), 5.45 (s, 1 H, C=CH), 6.80 (d, J = 8.1 Hz, 1 H, CH), 7.12 (t, J = 7.9 Hz, 1 H, CH), 7.13 (t, J = 8.1 Hz, 1 H, CH), 7.37 (t, J = 7.9 Hz, 2 H, CH), 7.43 (dt, J = 8.1, 1.1 Hz, 1 H, CH), 7.76 (d, J = 8.1 Hz, 1 H, CH), 7.86 (d, J = 7.9 Hz, 2 H, CH), 9.69 (br s, 1 H, NH), 11.05 (br s, 1 H, NH). 13C NMR (125.8 MHz, acetone-d 6): δ = 51.41 and 53.16 (2 OCH3), 97.75 (C=CH), 120.93, 120.97, 123.26 and 124.79 (4 CH), 126.26 (C=CH), 129.20, 129.51 and 132.18 (3 CH), 139.97, 141.36 and 146.73 (3 C), 165.66 (NC=O), 167.26 and 168.72 (2 OC=O).
  • 24 Typical Procedure for the Preparation of Compounds 4a–l, Exemplified with 4a A mixture of isatoic anhydride (0.163 g, 1 mmol) and aniline (0.093 g, 1 mmol) was stirred under solvent-free conditions at 70 °C for 40 min. After nearly complete conversion into anthranilamide, as indicated by TLC monitoring, dimethyl acetylenedicarboxylate (0.142 g, 1 mmol) and N-sulfonic acid pyridinium chloride (0.04 g, 20 mol%) were added over 3 min and stirring was continued for 50 min. Next, the reaction mixture was cooled to room temperature and was allowed to stir for 30 min in H2O. The white precipitate was filtered, washed with H2O (3 × 2 mL), dried, and then recrystallized from of H2O–EtOH (1:1) to give 4a as white crystals. Methyl 2-[(Methoxycarbonyl)methyl]-1,2,3,4-tetrahydro-4-oxo-3-phenylquinazoline-2-carboxylate (4a) White crystals, mp 156 °C, yield 0.332 g (94%). IR (KBr): 3368 (NH), 1729, 1668 and 1655 (C=O), 1594, 1531, 1508, 1438, 1370, 1324, 1283, 1207, 1154, 1031, 971, 887, 799, 755, 689, 627, 512, 472 cm–1. 1H NMR (500.13 MHz, CDCl3): δ = 2.91 and 2.95 (2 d, ΑΒ system, 2 J = 16.0 Hz, 2 H, CH A H BCO2CH3), 3.63 and 3.68 (2 s, 6 H, 2 OCH3), 6.22 (s, 1 H, NH), 6.75 (d, J = 8.1 Hz, 1 H, CH), 6.90 (t, J = 8.1 Hz, 1 H, CH), 7.26 (d, J = 7.1 Hz, 2 H, 2 CH), 7.36 (t, J = 7.1 Hz, 1 H, CH), 7.41 (t, J = 8.1 Hz, 1 H, CH), 7.44 (t, J = 7.1 Hz, 2 H, 2 CH), 7.93 (d, J = 8.1 Hz, 1 H, CH). 13C (125.8 MHz, CDCl3): δ = 41.50 (CH2), 52.24 and 53.22 (2 OCH3), 76.11 (NCN), 114.61 (CH), 115.69 (C), 119.90, 128.75, 128.90, 129.47, 130.21 and 134.07 (6 CH), 137.34 and 144.72 (2 C), 163.34 (NC=O), 170.34 and 170.61 (2 OC=O). Analytical Data for Novel Products Ethyl 2-[(Ethoxycarbonyl)methyl]-3-(4-chlorophenyl)1,2,3,4-tetrahydro-4-oxoquinazoline-2-carboxylate (4j) White crystals, mp 143 °C, yield 0.371 g (89%). IR (KBr): 3312 (NH), 1744, 1640 and 1622 (C=O), 1511, 1487, 1450, 1412, 1370, 1360, 1331, 1232, 1183, 1112, 1025, 974, 738, 688, 630, 512 cm–1. 1H NMR (300.13 MHz, CDCl3): δ = 1.09 and 1.21 (2 t, J = 7.1 Hz, 6 H, 2 OCH2CH 3), 2.82 and 2.90 (2 d, 2 J = 15.8 Hz, 2 H, CH 2CO2C2H5), 4.04–4.15 (m, 4 H, OCH 2CH3), 6.24 (s, 1 H, NH), 6.75 (d, J = 8.0 Hz, 1 H, CH), 6.89 (dt, J = 8.0, 1.0 Hz, 1 H, CH), 7.24 (d, J = 8.0 Hz, 2 H, 2 CH), 7.35 (dt, J = 8.0, 1.0 Hz, 1 H, CH), 7.39 (d, J = 8.0 Hz, 2 H, 2 CH), 7.89 (d, J = 8.0 Hz, 1 H, CH). 13C NMR (75.5 MHz, CDCl3): δ = 13.81 and 13.92 (2 OCH2 CH3), 41.46 (CH2CO2C2H5), 61.54 and 62.61 (2 OCH2CH3), 75.92 (NCN), 114.68 (CH), 115.67 (C), 119.95, 128.76, 129.59, 131.75 and 134.13 (5 CH), 134.63, 135.84 and 144.93 (3C), 163.51 (NC=O), 169.56 and 170.04 (OC=O). Ethyl 2-[(Ethoxycarbonyl)methyl]-3-benzyl-1,2,3,4-tetrahydro-4-oxoquinazoline-2-carboxylate (4k) White crystals, mp 136–138 °C, yield 0.361 g (91%). IR (KBr): 3306 (NH), 1736, 1640 and 1617 (C=O), 1523, 1491, 1444, 1392, 1371, 1365, 1328, 1237, 1201, 1120, 1030, 981, 743, 699, 631, 515 cm–1. 1H NMR (500.13 MHz, CDCl3): δ = 1.05 and 1.25 (2 t, J = 7.1 Hz, 6 H, 2 OCH2CH 3), 2.88 and 3.26 (2 d, 2 J = 16.2 Hz, 2 H, CH 2CO2C2H5), 3.96 and 4.01 (2 dq, ABX3 system, 2 J = 11.6 Hz, 3 J = 7.1 Hz, 2 H, OCH A H BCH3), 4.09–4.18 (m, 2 H, OCH 2CH3), 4.64 and 5.13 (2 d, 2 J = 16.5 Hz, 2 H, NCH2), 6.08 (s, 1 H, NH), 6.70 (d, J = 8.0 Hz, 1 H, CH), 6.89 (t, J = 8.0 Hz, 1 H, CH), 7.22 (t, J = 7.0 Hz, 1 H, CH), 7.27 (d, J = 7.0 Hz, 2 H, 2 CH), 7.31 (t, J = 7.1 Hz, 2 H, 2 CH), 7.35 (dt, J = 8.0, 1.5 Hz, 1 H, CH), 7.94 (d, J = 8.0 Hz, 2 H, CH). 13C NMR (125.8 MHz, CDCl3): δ = 13.74 and 14.02 (2 OCH2 CH3), 40.52 (CH2CO2C2H5), 45.58 (NCH2), 61.50 and 62.54 (2 OCH2CH3), 75.54 (NCN), 114.44 (CH), 114.79 (C), 119.58, 126.86, 127.09, 128.58, 128.72 and 133.99 (6 CH), 138.11 and 144.76 (2 C), 163.60 (NC=O), 169.55 and 170.47 (OC=O). Ethyl 2-[(Ethoxycarbonyl)methyl]-3-(4-methylbenzyl)-1,2,3,4-tetrahydro-4-oxoquinazoline-2-carboxylate (4l) White crystals, mp 137 °C, yield 0.370 g (90%). IR (KBr): 3308 (NH), 1740, 1641 and 1619 (C=O), 1521, 1495, 1452, 1399, 1374, 1359, 1332, 1239, 1192, 1118, 1033, 983, 747, 698, 632, 514 cm–1. 1H NMR (300.13 MHz, CDCl3): δ = 1.06 and 1.25 (2 t, J = 7.1 Hz, 6 H, 2 OCH2CH 3), 2.32 (s, 3 H, CH3), 2.88 and 3.27 (2 d, 2 J = 16.2 Hz, 2 H, CH 2CO2C2H5), 3.94 and 4.01 (2 dq, ABX3 system, 2 J = 11.5 Hz, 3 J = 7.1 Hz, 2 H, OCH A H BCH3), 4.08–4.20 (m, 2 H, OCH 2CH3), 4.57 and 5.11 (2 d, 2 J = 16.4 Hz, 2 H, NCH2), 6.08 (s, 1 H, NH), 6.69 (d, J = 8.0 Hz, 1 H, CH), 6.88 (dt, J = 8.0, 1.0 Hz, 1 H, CH), 7.10 (d, J = 8.0 Hz, 2 H, 2 CH), 7.16 (d, J = 8.0 Hz, 2 H, 2 CH), 7.33 (dt, J = 8.0, 1.5 Hz, 1 H, CH), 7.94 (dd, J = 8.0, 1.4 Hz, 2 H, CH). 13C NMR (75.5 MHz, CDCl3): δ = 13.70 and 13.99 (2 OCH2 CH3), 40.50 (CH2CO2C2H5), 45.34 (NCH2), 61.45 and 62.49 (2 OCH2CH3), 75.56 (NCN), 114.33 (CH), 114.79 (C), 119.50, 126.80, 128.67 and 129.19 (4 CH), 133.90 (C), 135.01 (CH), 136.63 and 144.69 (2 C), 163.54 (NC=O), 169.56 and 170.51 (OC=O).