Synlett, Table of Contents Synlett 2020; 31(11): 1126-1128DOI: 10.1055/s-0039-1690902 letter © Georg Thieme Verlag Stuttgart · New YorkHantzsch-Like Three-Component Synthesis of 9,10-Dihydro-3H-10a-azaphenanthrene-2,4-dicarbonitriles Fatma M. Saleh , Hamdi M. Hassaneen , Ismail A. Abdelhamid ∗Recommend Article Abstract Buy Article All articles of this category 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 Key wordsmulticomponent reaction - Hantzsch reaction - Michael reaction - aminocrotononitrile - pyridoisoquinolines - azaphenanthrenedicarbonitriles Full Text References References and Notes 1 Vohra RK, Bruneau C, Renaud J.-L. Adv. Synth. Catal. 2006; 348: 2571 2 Sridharan V, Perumal PT, Avendaño C, Menéndez JC. Tetrahedron 2007; 63: 4407 3 Kumar A, Maurya RA. Tetrahedron 2008; 64: 3477 4 Sridhar R, Perumal PT. Tetrahedron 2005; 61: 2465 5 Wang G.-W, Miao C.-B. Green Chem. 2006; 8: 1080 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 8 Rueffer M, Amann M, Zenk MH. Plant Cell Rep. 1986; 5: 182 9 Huang L, Shi A, He F, Li X. Bioorg. Med. Chem. 2010; 18: 1244 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 11 Mohamed MF, Hassaneen HM, Abdelhamid IA. Eur. J. Med. Chem. 2018; 143: 532 12 Yang X, Yang S, Chai H, Yang Z, Lee RJ, Liao W, Teng L. PLoS One 2015; 10: e0136649 13 Elwan NM, Abdelhadi HA, Abdallah TA, Hassaneen HM. Tetrahedron 1996; 52: 3451 14 Maryanoff BE, McComsey DF, Costanzo MJ, Setler PE, Gardocki JF, Shank RP, Schneider CR. J. Med. Chem. 1984; 27: 943 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 16 Buchanan MS, Davis RA, Duffy S, Avery VM, Quinn RJ. J. Nat. Prod. 2009; 72: 1541 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 21 Sanad SM. H, Kassab RM, Abdelhamid IA, Elwahy AH. M. Heterocycles 2016; 92: 910 22 Salama SK, Mohamed MF, Darweesh AF, Elwahy AH. M, Abdelhamid IA. Bioorg. Chem. 2017; 71: 19 23 Abdella AM, Mohamed MF, Mohamed AF, Elwahy AH. M, Abdelhamid IA. J. Heterocycl. Chem. 2018; 55: 498 24 Abdelmoniem AM, Ghozlan SA. S, Abdelmoniem DM, Elwahy AH. M, Abdelhamid IA. J. Heterocycl. Chem. 2017; 54: 2844 25 Abdelhamid IA, Darwish ES, Nasra MA, Abdel-Gallil FM, Fleita DH. Synthesis 2010; 1107 26 Afon’kin AA, Kostrikin ML, Shumeiko AE, Popov AF. Russ. J. Org. Chem. 2011; 47: 731 27 Openshaw HT, Hittak N. J. Chem. Soc. 1961; 4939 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 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. Supplementary Material Supplementary Material Supporting Information
