Synlett 2018; 29(04): 493-496
DOI: 10.1055/s-0036-1591509
letter
© Georg Thieme Verlag Stuttgart · New York

Green Synthesis of Pyrido[2,1-a]isoquinolines and Pyrido[1,2-a]quinolines by Using ZnO Nanoparticles

Maryam Ghazvini
a  Department of Chemistry, Payame Noor University, PO Box 3971189451, Tehran, Iran
,
Fatemeh Sheikholeslami-Farahani*
b  Department of Chemistry, Firoozkooh Branch, Islamic Azad University, Firoozkooh, Iran
,
Somayeh Soleimani-Amiri
c  Department of Chemistry, Karaj Branch, Islamic Azad University, Karaj, Iran
,
Masoomeh Salimifard
d  Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran
,
Rezvaneh Rostamian
d  Department of Chemistry, Qaemshahr Branch, Islamic Azad University, Qaemshahr, Iran
› Author Affiliations
We gratefully acknowledge financial support provided by the Islamic Azad University of Firoozkooh, Karaj and Payame Noor University.
Further Information

Publication History

Received: 27 August 2017

Accepted after revision: 04 October 2017

Publication Date:
07 December 2017 (online)


Abstract

Pyrido[2,1-a]isoquinoline and pyrido[1,2-a]quinoline derivatives have been produced in good yields by the reaction of isoquinoline or quinoline, activated acetylenic compounds, α-halo ketones, and triphenylphosphine in the presence of ZnO nanoparticles (NPs) as an efficient catalyst under solvent-free conditions at room temperature. The reaction workup is easy, and the products can be readily separated from the reaction mixture. ZnO NPs markedly improved the yield of the product. The catalyst showed significant reusable activity.

 
  • References and Notes

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  • 28 ZnO Nanoparticles NaOH (0.44 g) was dissolved in distilled H2O (75 mL) at r.t. Zn(OAc)2·2H2O (0.6 g) was added, and the solution and was heated at 80 °C for 1.5 h. The solution was then cooled to r.t., and the precipitate was collected by filtration and washed several times with distilled H2O and 96% EtOH. The solid ZnO NPs were dried in air at r.t. for 24 h. Pyrido [2,1-a]isoquinolines 5af; General Procedure To a stirred mixture of isoquinoline 1 (0.258 g, 2 mmol) and the appropriate activated acetylenic diester 2 (2 mmol) was added a mixture of Ph3P (4; 2 mmol), the appropriate alkyl bromide 3 (2 mmol), and ZnO NPs (10 mol%). The resulting mixture was stirred at r.t. for about 5 h until the reaction was complete (TLC). H2O (15 mL) was poured onto the reaction mixture, and the solids were collected by filtration. The catalyst was separated by washing the solid with EtOAc (2 × 3 mL) and filtering. The EtOAc was evaporated and the residue was washed with Et2O. Methyl 1-[Ethoxy(oxo)acetyl]-2-methoxy-6H-pyrido[2,1-a]isoquinoline-4-carboxylate (5a) Yellow powder; yield: 0.75 g (95%); mp 135–137 °C. IR (KBr): 1738, 1732, 1725, 1692, 1575, 1486, 1293 cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 1.02 (t, J = 7.3 Hz, 3 H, Me), 3.75 (s, 3 H, MeO), 3.78 (s, 3 H, MeO), 4.22 (q, J = 7.3 Hz, 2 H, CH2O), 5.18 (s, 1 H, CH), 5.62 (d, J = 7.5 Hz, 1 H, CH), 5.78 (s, 1 H, CH), 7.12 (d, J = 7.5 Hz, 1 H, CH), 7.28 (t, J = 7.6 Hz, 1 H, CH), 7.32 (t, J = 7.6 Hz, 1 H, CH), 7.45 (d, J = 7.6 Hz, 1 H, CH), 7.56 (d, J = 7.6 Hz, 1 H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 13.8 (Me), 52.3 (MeO), 55.7 (CH), 58.4 (MeO), 62.3 (CH2O), 102.3 (CH), 106.3 (CH), 121.2 (CH), 121.8 (C), 126.7 (CH), 127.4 (CH), 127.8 (CH), 128.3 (CH), 136.2 (C), 141.5 (C), 142.2 (C), 155.3 (C), 160.2 (C=O), 166.4 (C=O), 182.7 (C=O). MS (EI-MS): m/z (%) = 369 [M] (15), 338 (62), 129 (100), 31 (100). Anal. Calcd for C20H19NO6 (369.37): C 65.03, H 5.18, N 3.79; Found: C 65.18, H 5.34, N 3.94. Ethyl 2-Ethoxy-1-[ethoxy(oxo)acetyl]-6H-pyrido[2,1-a]isoquinoline-4-carboxylate (5b) Yellow powder; yield: 0.70 g (93%); mp 142–144 °C. IR (KBr): 1742, 1736, 1727, 1687, 1562, 1485, 1285 cm –1. 1H NMR (500.1 MHz, CDCl3): δ = 0.98 (t, J = 7.3 Hz, 3 H, Me), 1.06 (t, J = 7.4 Hz, 3 H, Me), 1.12 (t, J = 7.4 Hz, 3 H, Me), 4.12 (q, J = 7.4 Hz, 2 H, CH2O), 4.18 (q, J = 7.4 Hz, 2 H, CH2O), 4.25 (q, J = 7.4 Hz, 2 H, CH2O), 5.22 (s, 1 H, CH), 5.68 (d, J = 7.6 Hz, 1 H, CH), 5.82 (s, 1 H, CH), 7.16 (d, J = 7.6 Hz, 1 H, CH), 7.33 (t, J = 7.6 Hz, 1 H, CH), 7.36 (t, J = 7.6 Hz, 1 H, CH), 7.47 (d, J = 7.6 Hz, 1 H, CH), 7.63 (d, J = 7.6 Hz, 1 H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 13.5 (Me), 14.2 (Me), 14.8 (Me), 55.6 (CH), 61.3 (CH2O), 62.4 (CH2O), 62.8 (CH2O), 102.5 (CH), 106.7 (CH), 121.5 (CH), 122.3 (C), 127.2 (CH), 127.7 (CH), 128.2 (CH), 128.7 (CH), 136.5 (C), 141.8 (C), 142.5 (C), 155.6 (C), 160.8 (C=O), 166.7 (C=O), 183.2 (C=O). MS (EI-MS): m/z (%) = 397 [M] (15), 352 (68), 129 (100), 45 (86). Anal. Calcd for C22H23NO6 (397.42): C 66.49, H 5.83, N 3.52; Found: C 66.63, H 5.98, N 3.73. Methyl 2-Methoxy-1-(4-nitrobenzoyl)-6H-pyrido[2,1-a]isoquinoline-4-carboxylate (5f) Yellow powder; yield: 0.67 g (80%); mp 195–197 °C. IR (KBr): 1738, 1729, 1695, 1593, 1487, 1295 cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 3.78 (s, 3 H, MeO), 3.85 (s, 3 H, MeO), 5.47 (s, 1 H, CH), 5.74 (d, J = 7.8 Hz, 1 H, CH), 5.93 (s, 1 H, CH), 7.22 (d, J = 7.8 Hz, 2 H, 2 CH), 7.29 (d, J = 7.8 Hz, 1 H, CH), 7.36 (t, J = 7.6 Hz, 1 H, CH), 7.42 (t, J = 7.6 Hz, 1 H, CH), 7.52 (d, J = 7.6 Hz, 1 H, CH), 7.63 (d, J = 7.6 Hz, 1 H, CH), 7.98 (d, J = 7.8 Hz, 2 H, 2 CH). 13C NMR (125.7 MHz, CDCl3): δ = 52.6 (MeO), 57.2 (CH), 58.3 (MeO), 101.4 (CH), 105.4 (CH), 113.6 (C), 118.3 (CH), 122.6 (2 CH), 125.7 (CH), 126.2 (CH), 126.8 (CH), 127.3 (CH), 130.2 (2 CH), 134.3 (C), 140.2 (C), 142.3 (C), 143.8 (C), 151.6 (C), 160.3 (C=O), 161.5 (C), 194.2 (C=O). MS (EI-MS): m/z (%) = 418 [M] (15), 387 (64), 129 (100), 31 (100). Anal. Calcd for C23H18N2O6 (418.39): C 66.02, H 4.34, N 6.70; Found: C 66.18, H 4.49, N 6.87.
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  • 31 Pyrimido[1,2-a]quinolines 7ad; General Procedure To a stirred mixture of quinoline (1; 0.258 g, 2 mmol) and the appropriate activated acetylenic diester 2 (2 mmol) was added a mixture of Ph3P (4; 2 mmol), the appropriate alkyl bromide 3 (2 mmol), and ZnO NPs (10 mol%), The resulting mixture was stirred for about 5 h until the reaction was complete (TLC), then H2O (15 mL) was poured onto the reaction mixture and the solids were collected by filtration. The catalyst was separated by washing the solids with EtOAc (2 × 3 mL) and filtering. The product was then obtained by evaporating the EtOAc and washing the residue with Et2O. Methyl 4-[Ethoxy(oxo)acetyl]-3-methoxy-4aH-pyrido[1,2-a]quinoline-1-carboxylate (7a)Yellow powder; yield: 0.72 g (92%); mp 143–145 °C. IR (KBr): 1737, 1733, 1727, 1694, 1576, 1488, 1284 cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 1.08 (t, J = 7.3 Hz, 3 H, Me), 3.78 (s, 3 H, MeO), 3.82 (s, 3 H, MeO), 4.25 (q, J = 7.3 Hz, 2 H, CH2O), 5.22 (d, J = 4.5 Hz, 1 H, CH), 5.78 (s, 1 H, CH), 6.63 (d, J = 7.6 Hz, 1 H, CH), 6.95 (t, J = 7.5 Hz, 1 H, CH), 7.14 (d, J = 7.6 Hz, 1 H, CH), 7.24 (t, J = 7.6 Hz, 1 H, CH), 7.32 (d, J = 7.6 Hz, 1 H, CH), 7.43 (d, J = 7.6 Hz, 1 H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 3.6 (Me), 51.2 (CH), 52.3 (MeO), 58.4 (MeO), 62.3 (CH2O), 102.4 (CH), 115.3 (CH), 116.7 (C), 122.3 (CH), 123.4 (CH), 126.4 (C), 129.7 (CH), 132.2 (CH), 135.6 (CH), 141.2 (C), 144.3 (C), 151.2 (C), 165.2 (C=O), 169.3 (C=O), 182.3 (C=O). MS (EI-MS): m/z (%) = 369 [M] (10), 338 (68), 129 (100), 31 (100). Anal. Calcd for C20H19NO6 (369.37): C 65.03, H 5.18, N 3.79; Found: C 65.22, H 5.38, N 3.96. Ethyl 3-Ethoxy-4-[ethoxy(oxo)acetyl]-4aH-pyrido[1,2-a]quinoline-1-carboxylate (7b)Yellow powder; yield: 0.70 g (90%); mp 147–149 °C. IR (KBr): 1742, 1736, 1727, 1687, 1562, 1485, 1285 cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 1.02 (t, J = 7.3 Hz, 3 H, Me), 1.12 (t, J = 7.4 Hz, 3 H, Me), 1.18 (t, J = 7.4 Hz, 3 H, Me), 4.10 (q, J = 7.4 Hz, 2 H, CH2O), 4.25 (q, J = 7.4 Hz, 2 H, CH2O), 4.28 (q, J = 7.4 Hz, 2 H, CH2O), 5.25 (d, J = 4.3 Hz, 1 H, CH), 5.82 (s, 1 H, CH), 6.75 (d, J = 7.6 Hz, 1 H, CH), 7.03 (t, J = 7.5 Hz, 1 H, CH), 7.15 (d, J = 7.6 Hz, 1 H, CH), 7.28 (t, J = 7.6 Hz, 1 H, CH), 7.34 (d, J = 7.6 Hz, 1 H, CH), 7.46 (d, J = 7.6 Hz, 1 H, CH). 13C NMR (125.7 MHz, CDCl3): δ = 13.6 (Me), 13.8 (Me), 14.6 (Me), 51.7 (CH), 61.7 (CH2O), 62.6 (CH2O), 63.2 (CH2O), 102.3 (CH), 115.4 (CH), 116.5 (C), 122.7 (CH), 123.6 (CH), 126.6 (C), 130.2 (CH), 132.3 (CH), 136.3 (CH), 141.4 (C), 144.7 (C), 151.6 (C), 165.5 (C=O), 169.7 (C=O), 182.5 (C=O). MS (EI-MS): m/z (%) = 397 [M] (15), 352 (84), 129 (100), 45 (88). Anal. Calcd for C22H23NO6 (397.42): C 66.49, H 5.83, N 3.52; Found: C 66.65, H 6.02, N 3.76. Methyl 3-Methoxy-4-(4-methoxybenzoyl)-4aH-pyrido[1,2-a]quinoline-1-carboxylate (7d) Yellow powder; yield: 0.70 g (87%); mp 176–178 °C. IR (KBr): 1735, 1726, 1685, 1587, 1486 cm–1. 1H NMR (500.1 MHz, CDCl3): δ = 3.72 (s, 3 H, MeO), 3.78 (s, 3 H, MeO), 3.85 (s, 3 H, MeO), 5.84 (d, J = 4.3 Hz, 1 H, CH), 5.95 (s, 1 H, CH), 6.86 (d, J = 7.5 Hz, 1 H, CH), 7.04 (d, J = 7.8 Hz, 2 H, 2 CH), 7.12 (d, J = 7.6 Hz, 1 H, CH), 7.23 (t, J = 7.6 Hz, 1 H, CH), 7.32 (t, J = 7.6 Hz, 1 H, CH), 7.32 (t, J = 7.6 Hz, 1 H, CH), 7.38 (d, J = 7.6 Hz, 1 H, CH), 8.12 (d, = 7.8 Hz, 2 H, 2 CH). 13C NMR (125.7 MHz, CDCl3): δ = 51.5 (CH), 52.3 (MeO), 55.4 (MeO), 58.6 (MeO), 101.2 (CH), 105.4 (C), 112.6 (2 CH), 114.3 (CH), 120.3 (CH), 122.4 (CH), 126.3 (C), 130.4 (CH), 132.3 (2 CH), 132.7 (C), 133.4 (CH), 140.6 (CH), 141.8 (C), 142.6 (C), 157.2 (C), 163.4 (C), 169.3 (C=O), 192.5 (C=O). MS (EI-MS): m/z (%) = 403 [M] (10), 372 (74), 129 (100), 31 (100). Anal. Calcd for C24H21NO5 (403.43): C 71.45, H 5.25, N 3.47; Found: C 71.61, H 5.39, N 3.65.