Molecular-Iodine-Promoted Synthesis of Dihydrobenzofuran-3,3-dicarbonitriles through a Novel Rearrangement

CSIR-IICT Communication No. IICT/pubs./2018/203.

Abstract

The title compounds were synthesized from 5,5-dimethyl­cyclohexane-1,3-dione, benzaldehyde, and malononitrile promoted by molecular iodine in basic medium via 2-amino-7,7-dimethyl-5-oxo-4-phenyl-5,6,7,8-tetrahydro-4H-chromene-3-carbonitrile, by a novel protocol. The protocol involves a novel rearrangement in which the 4H-chromene fragment dissociates to a cyclopropane moiety and rearranges to the five-membered compound 6,6-dimethyl-4-oxo-2-phenyl-4,5,6,7-tetrahydrobenzofuran-3,3(2H)-dicarbonitrile. Simple reaction conditions, excellent yields, and high compatibility are the advantages of this protocol.

Key words

dimedone - aromatic aldehydes - chromenes - triethylamine - rearrangement

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• 29 2-(Het)aryl-6,6-Dimethyl-4-oxo-2-phenyl-4,5,6,7-tetrahydro­benzofuran-3,3(2H)-dicarbonitriles (2a–r); General Procedure A round-bottomed flask equipped with a reflux condenser and stopper was charged with the appropriate nitrile 1 (1.02 mmol), I₂ (1.02 mmol), Et₃N (2.04 mmol), and DCE (20 mL), and the mixture was refluxed with stirring for 2 h. When the reaction was complete (TLC), the homogeneous reaction mass was concentrated under reduced pressure and the residue was transferred to a separatory funnel, washed with H₂O (3 × 20 mL), and extracted with EtOAc (20 mL). The organic layer was dried (­Na₂SO₄) and concentrated under reduced pressure. The residue was purified by column chromatography (silica gel, 20–40% EtOAc–hexane). 6,6-Dimethyl-4-oxo-2-phenyl-4,5,6,7-tetrahydro-1-benzo­furan-3,3(2H)-dicarbonitrile (2a) Colorless solid; yield: 0.232 g (80%); mp 142–144°C. IR (KBr): 2952, 2238, 1655, 1412, 1120, 1059, 985, 850, 776 cm^–1. ¹H NMR (500 MHz, CDCl₃): δ = 7.55–7.46 (m, 3 H), 7.45–7.41 (m, 2 H), 6.14 (s, 1 H), 2.64–2.50 (m, 2 H), 2.46–2.31 (m, 2 H), 1.19–1.15 (s, 6 H). ¹³C NMR (100 MHz, CDCl₃): δ = 190.4, 179.2, 131.4, 130.9, 129.3, 125.9, 112.8, 110.2, 108.2, 92.4, 50.4, 42.5, 37.8, 34.3, 28.8, 27.9. ESI-MS: m/z = 293 [M + H]⁺. HRMS (ESI): m/z [M + H]⁺ calcd for C₁₈H₁₇N₂O₂: 293.1300; found: 293.1284.