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

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

• References and Notes

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• 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.