Download PDF
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 AffiliationsWe 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)

    Permissions and Reprints All articles of this category


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.

Key words

pyridoisoquinolines - pyridoquinolines - solvent-free synthesis - dialkyl acetylenedicarboxylates - nanoparticles - zinc oxide
 

  • References and Notes

  • 1 Hermecz I. Vasvári-Debreczy L. Mátyus P. In Comprehensive Heterocyclic Chemistry II . Vol. 8, Chap. 8.23. Katritzky AR. Rees CW. Scriven EV. F. Pergamon; Oxford: 1996: 563
    CrossrefGoogle Scholar
    • 2a Jayaraman M. Fox BM. Hollingshead M. Kohlhagen G. Pommier Y. Cushman M. J. Med. Chem. 2002; 45: 242
      CrossrefPubMed
    • 2b Goldberg DR. Butz T. Cardozo MG. Eckner RJ. Hammach A. Huang J. Jakes S. Kapadia S. Kashem M. Lukas S. Morwick TM. Panzenbeck M. Patel U. Pav S. Peet GW. Peterson JD. Prokopowicz AS. III. Snow RJ. Sellati R. Takahashi H. Tan J. Tschantz MA. Wang X.-J. Wang Y. Wolak J. Xiong P. Moss N. J. Med. Chem. 2003; 46: 1337
      CrossrefPubMed
    • 2c Griffin RJ. Fontana G. Golding BT. Guiard S. Hardcastle IR. Leahy JJ. J. Martin N. Richardson C. Rigoreau L. Stockley M. Smith GC. M. J. Med. Chem. 2005; 48: 569
      CrossrefPubMed
    • 2d Goldbrunner M. Loidl G. Polossek T. Mannschreck A. von Angerer E. J. Med. Chem. 1997; 40: 3524
      CrossrefPubMed
  • 3 Ruppert D. Weithmann KU. Life Sci. 1982; 31: 2037
    CrossrefPubMed
  • 4 Swinbourne JF. Hunt HJ. Klinkert G. Adv. Heterocycl. Chem. 1987; 23: 103
  • 5 Kidwai M. Bhushan KR. Sapra P. Saxena RK. Gupta P. Bioorg. Med. Chem. 2000; 8: 69
    CrossrefPubMed
    • 6a Touré BB. Hall DG. Chem. Rev. 2009; 109: 4439
      CrossrefPubMed
    • 6b Balme G. Bossharth E. Monteiro N. Eur. J. Org. Chem. 2003; 4101
    • 6c Hulme C. Gore V. Curr. Med. Chem. 2003; 10: 51
      CrossrefPubMed
    • 6d Zhu J. Eur. J. Org. Chem. 2003; 1133
    • 6e Tietze LF. Modi A. Med. Res. Rev. 2000; 20: 304
      CrossrefPubMed
    • 6f Maiti S. Biswas S. Jana U. J. Org. Chem. 2010; 75: 1674
      CrossrefPubMed
    • 6g Gu YL. Green Chem. 2012; 14: 2091
      Crossref
    • 6h Gers CF. Nordmann J. Kumru C. Frank W. Müller TJ. J. J. Org. Chem. 2014; 79: 3296
      CrossrefPubMed
    • 6i Mondal A. Mukhopadhyay C. ACS Comb. Sci. 2015; 17: 404
      CrossrefPubMed
  • 8 Erlanson DA. McDowell RS. O’Brien T. J. Med. Chem. 2004; 47: 3463
    CrossrefPubMed
  • 11 Shingate BB. Org. Chem.: Curr. Res. 2012; 1: e107; DOI: 10.4172/2161 >0401.1000e107
    • 12a Keivanloo A. Kazemi SS. Nasr-Isfahani H. Bamoniri A. Tetrahedron 2016; 72: 6536
      Crossref
    • 12b Hajduk PJ. Greer J. Nat. Rev. Drug Discovery 2007; 6: 211
      CrossrefPubMed
  • 13 Microwaves in Organic Synthesis . 2nd ed.; Loupy A. Wiley-VCH; Weinheim: 2006
    Google Scholar
  • 14 Chmura AJ. Davidson MG. Frankis CJ. Jones MD. Lunn MD. Chem. Commun. 2008; 1293
    PubMed
  • 15 Góra M. Kozik B. Jamroży K. Łuczyński MK. Brzuzan P. Woźny M. Green Chem. 2009; 11: 863
    Crossref
    • 16a Hasaninejad A. Shekouhy M. Zare A. Catal. Sci. Technol. 2012; 2: 201
      Crossref
    • 16b Hasaninejad A. Zare A. Shekouhy M. Ameri-Rad J. Green Chem. 2011; 13: 958
      Crossref
    • 16c Hasaninejad A. Rasekhi Kazerooni M. Zare A. Catal. Today 2012; 196: 148
      Crossref
  • 17 Rostamizadeh S. Nojavan M. Aryan R. Isapoor E. Azad M. J. Mol. Catal. A: Chem. 2013; 374–375: 102
  • 18 Beydoun D. Amal R. Low G. McEvoy S. J. Nanopart. Res. 1999; 1: 439
    Crossref
  • 19 Comparelli R. Fanizza E. Curri ML. Cozzoli PD. Mascolo G. Agostiano A. Appl. Catal., B 2005; 60: 1
    Crossref
  • 20 Moghaddam FM. Saeidian H. Mater. Sci. Eng., B 2007; 139: 265
    Crossref
  • 21 Mirjafary H. Saeidian H. Sadeghi A. Moghaddam FM. Catal. Commun. 2008; 9: 299
    Crossref
  • 22 Gupta M. Paul S. Gupta R. Loupy A. Tetrahedron Lett. 2005; 46: 4957
    Crossref
  • 23 Lietti L. Tronconi E. Forzatti PJ. Busca G. J. Mol. Catal. 1989; 55: 43
    Crossref
  • 24 Eskandari K. Karami B. Khodabakhshi S. Chem. Heterocycl. Compd. 2015; 50: 1658
    Crossref
  • 25 Hossaini Z. Ghambarian M. Afshari Sharif Abad S. Mohtat B. Lett. Org. Chem. 2015; 12: 176
    Crossref
  • 26 Hossaini Z. Rostami-Charati F. Ghasemian M. Afshari Sharif Abad S. Synlett 2015; 26: 1222
    Article in Thieme Connect
  • 27 Hossaini Z. Sheikholeslami-Farahani F. Rostami-Charati F. Comb. Chem. High Throughput Screening 2014; 17: 804
    CrossrefPubMed
  • 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 5a–f; 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.
  • 29 Sabbaghan M. Anaraki Firooz A. Ahmadi VJ. J. Mol. Liq. 2012; 175: 135
    Crossref
  • 30 Mehrabi Matin B. Mortazavi Y. Khodadadi AA. Abbasi A. Anaraki Firooz A. Sens. Act. B: Chem. 2010; 151: 140
    Crossref
  • 31 Pyrimido[1,2-a]quinolines 7a–d; 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, J = 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.