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Synlett 2020; 31(11): 1126-1128
DOI: 10.1055/s-0039-1690902
letter
© Georg Thieme Verlag Stuttgart · New York

Hantzsch-Like Three-Component Synthesis of 9,10-Dihydro-3H-10a-azaphenanthrene-2,4-dicarbonitriles

Fatma M. Saleh
,
Hamdi M. Hassaneen
,
Ismail A. Abdelhamid  ∗
Further Information

Publication History

Received: 08 March 2020

Accepted after revision: 02 April 2020

Publication Date:
22 April 2020 (online)

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Abstract

A novel series of 9,10-dihydro-3H-10a-azaphenanthrene-2,4-dicarbonitrile derivatives that contain a bridgehead nitrogen were prepared by a three-component reaction of aldehydes, 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile, and 3-aminocrotononitrile in acetic acid.

Key words

multicomponent reaction - Hantzsch reaction - Michael reaction - aminocrotononitrile - pyridoisoquinolines - azaphenanthrenedicarbonitriles

Supporting Information

    Supporting information for this article is available online at https://doi.org/10.1055/s-0039-1690902.
  • Supporting Information
 

  • References and Notes

  • 1 Vohra RK, Bruneau C, Renaud J.-L. Adv. Synth. Catal. 2006; 348: 2571
    CrossrefSearch in Google Scholar
  • 2 Sridharan V, Perumal PT, Avendaño C, Menéndez JC. Tetrahedron 2007; 63: 4407
    CrossrefSearch in Google Scholar
  • 3 Kumar A, Maurya RA. Tetrahedron 2008; 64: 3477
    CrossrefSearch in Google Scholar
  • 4 Sridhar R, Perumal PT. Tetrahedron 2005; 61: 2465
    CrossrefSearch in Google Scholar
  • 5 Wang G.-W, Miao C.-B. Green Chem. 2006; 8: 1080
    CrossrefSearch in Google Scholar
  • 6 Yang J, Wang C, Xie X, Li H, Li Y. Eur. J. Org. Chem. 2010; 4189
  • 7 Galat A. J. Am. Chem. Soc. 1951; 73: 3654
    CrossrefSearch in Google Scholar
  • 8 Rueffer M, Amann M, Zenk MH. Plant Cell Rep. 1986; 5: 182
    CrossrefPubMedSearch in Google Scholar
  • 9 Huang L, Shi A, He F, Li X. Bioorg. Med. Chem. 2010; 18: 1244
    CrossrefPubMedSearch in Google Scholar
  • 10 Mukherjee A, Dutta S, Shanmugavel M, Mondhe DM, Sharma PR, Singh SK, Saxena AK, Sanyal U. J. Exp. Clin. Cancer Res. 2010; 29: 175
    CrossrefPubMedSearch in Google Scholar
  • 11 Mohamed MF, Hassaneen HM, Abdelhamid IA. Eur. J. Med. Chem. 2018; 143: 532
    CrossrefPubMedSearch in Google Scholar
  • 12 Yang X, Yang S, Chai H, Yang Z, Lee RJ, Liao W, Teng L. PLoS One 2015; 10: e0136649
    CrossrefPubMedSearch in Google Scholar
  • 13 Elwan NM, Abdelhadi HA, Abdallah TA, Hassaneen HM. Tetrahedron 1996; 52: 3451
    CrossrefSearch in Google Scholar
  • 14 Maryanoff BE, McComsey DF, Costanzo MJ, Setler PE, Gardocki JF, Shank RP, Schneider CR. J. Med. Chem. 1984; 27: 943
    CrossrefPubMedSearch in Google Scholar
  • 15 Kashiwada Y, Aoshima A, Ikeshiro Y, Chen Y.-P, Furukawa H, Itoigawa M, Fujioka T, Mihashi K, Cosentino LM, Morris-Natschke SL, Lee K.-H. Bioorg. Med. Chem. 2005; 13: 443
    CrossrefPubMedSearch in Google Scholar
  • 16 Buchanan MS, Davis RA, Duffy S, Avery VM, Quinn RJ. J. Nat. Prod. 2009; 72: 1541
    CrossrefPubMedSearch in Google Scholar
  • 17 Boehringer M, Kuhn B, Mattei P, Narquizian R. US 7122555, 2006
  • 18 Boehringer M, Kuhn B, Luebbers T, Mattei P, Narquizian R, Wessel HP. US 7718666, 2010
  • 19 Abrecht S, Adam J.-M, Fettes A, Hildbrand S. US 201512674312, 2015
  • 20 Mohamed MF, Darweesh AF, Elwahy AH. M, Abdelhamid IA. RSC Adv. 2016; 6: 40900
    CrossrefSearch in Google Scholar
  • 21 Sanad SM. H, Kassab RM, Abdelhamid IA, Elwahy AH. M. Heterocycles 2016; 92: 910
    CrossrefSearch in Google Scholar
  • 22 Salama SK, Mohamed MF, Darweesh AF, Elwahy AH. M, Abdelhamid IA. Bioorg. Chem. 2017; 71: 19
    CrossrefPubMedSearch in Google Scholar
  • 23 Abdella AM, Mohamed MF, Mohamed AF, Elwahy AH. M, Abdelhamid IA. J. Heterocycl. Chem. 2018; 55: 498
    CrossrefSearch in Google Scholar
  • 24 Abdelmoniem AM, Ghozlan SA. S, Abdelmoniem DM, Elwahy AH. M, Abdelhamid IA. J. Heterocycl. Chem. 2017; 54: 2844
    CrossrefSearch in Google Scholar
  • 25 Abdelhamid IA, Darwish ES, Nasra MA, Abdel-Gallil FM, Fleita DH. Synthesis 2010; 1107
    Thieme Connect
  • 26 Afon’kin AA, Kostrikin ML, Shumeiko AE, Popov AF. Russ. J. Org. Chem. 2011; 47: 731
    CrossrefSearch in Google Scholar
  • 27 Openshaw HT, Hittak N. J. Chem. Soc. 1961; 4939
    Crossref
  • 28 Ajzert KI, Takács K. Liebigs Ann. 1987; 1061
  • 29 Awad EM, Elwan NM, Hassaneen HM, Linden A, Heimgartner H. Helv. Chim. Acta 2001; 84: 1172
    CrossrefSearch in Google Scholar
  • 30 2-Aryl-9,10-dimethoxy-4-methyl-6,7-dihydro-2H-pyrido[2,1-a]isoquinoline-1,3-dicarbonitriles 4a–g; General Procedure A mixture of the appropriate aldehyde 1a–g (1 mmol) and 2-(6,7-dimethoxy-3,4-dihydroisoquinolin-1-yl)acetonitrile (2; 1 mmol) was refluxed in HOAc (10 mL) for 5 min. 3-Aminocrotononitrile (3; 1 mmol) was then added, and refluxing was continued for 3 h. The excess solvent was evaporated under reduced pressure, and the crude product was crystallized from EtOH. 9,10-Dimethoxy-4-methyl-2-phenyl-6,7-dihydro-2H-pyrido[2,1-a]isoquinoline-1,3-dicarbonitrile (4a): Yellow crystals; yield: 288 mg (75%); mp 208–210 °C. IR (KBr): 2182 (CN) cm–1. 1H NMR (400 MHz, DMSO-d 6): δ = 2.31 (s, 3 H, CH3), 2.88–2.91 (m, 2 H, CH2), 3.54–3.59 (m, 1 H, CH2), 3.75 (s, 3 H, CH3O), 3.76–3.83 (m, 1 H, CH2), 3.88 (s, 3 H, CH3O), 4.46 (s, 1 H, H-2), 7.02 (s, 1 H, Ar-H), 7.34–7.42 (m, 5 H, Ph), 7.63 (s, 1 H, Ar-H). 13C NMR (100 MHz, DMSO-d 6): δ = 18.9 (Me), 28.6 (C-7), 42.1 (C-2), 44.2 (C-6), 56.1 (OMe), 56.2 (OMe), 82.2 (C-1), 85.1 (C-3), 111.2 (C-11), 111.3 (C-8), 119.6 (CN), 120.3 (CN), 121.6 (Ar-C), 127.8 (Ar-C), 128.3 (Ar-C), 129.5 (Ar-C), 131.8 (Ar-C), 143.7 (Ar-C), 146.3 (C10), 147.1 (C9), 150.4 (C4), 151.3 (C11b). Anal. Calcd for C24H21N3O2 (383.5): C, 75.18; H, 5.52; N, 10.96. Found: C, 75.04; H, 5.60; N, 10.87.