A Novel Synthesis of Aminofurans Using a Four-Component Reaction

Abstract

Protonation of the reactive intermediate produced in the reaction between triphenylphosphine and dialkyl acetylenedicarboxylates by carboxylic acid leads to vinylphosphonium salts, which undergo nucleophilic reaction with carboxylate anion to ­produce dialkyl (E)-2-aroyl-2-butenedioate. This intermediate is trapped with isocyanide to produce dialkyl 2-(alkylamino)-5-(aryl)-3,4-furandicarboxylate.

Key words

alkyl isocyanide - dialkyl acetylenedicarboxylate - carboxylic acid - multicomponent reaction - triphenylphosphine

References and Notes

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29

To a magnetically stirred solution of 4-nitrobenzoic acid (0.17 g, 1 mmol) and dimethyl acetylenedicarboxylate (0.14 g, 1 mmol) in anhyd CH₂Cl₂ (5 mL) was added dropwise a solution of triphenylphosphine (0.26 g, 1 mmol) and tert-butyl isocyanide (0.83 g, 1 mmol) in anhyd CH₂Cl₂ (3 mL) at r.t. over 20 min. The reaction mixture was stirred for 24 h. The solvent was removed under reduced pressure, and the residue was separated by silica gel (Merck 230-240 mesh) column chromatography using hexane-EtOAc mixture as eluent. The product 4a was obtained as orange crystals; yield: 74% (0.28 g); mp 177-179 °C. IR (KBr): 3445 (NH), 1724 (CO₂Me), 1669 (CO₂Me), 1504, 1468 (Ar), 1591, 1326 (NO₂), 1261, 1213, 1184, 1103 (CO) cm^-1. ¹H NMR (500.1 MHz, CDCl₃): δ = 1.52 (s, 9 H, CMe₃), 3.79 (s, 3 H, OMe), 3.96 (s, 3 H, OMe), 6.97 (s, 1 H, NH), 7.61 (d, ³ J _HH = 8.9 Hz, 2 H, 2 × CH of Ar), 8.22 (d, ³ J _HH = 8.9 Hz, 2 H, 2 × CH of Ar). ¹³C NMR: δ = 29.81 (CMe ₃), 51.43 (CMe₃), 53.03 (OMe), 53.13 (OMe), 89.65 (C₃ of furan), 117.51 (C₄ of furan), 123.95 (2 × CH of Ar), 124.40 (2 × CH of Ar), 134.99 (C_ipso), 138.36 (C_ipsoNO₂), 146.00 (C₅ of furan), 161.94 (C₂ of furan), 164.58 (CO₂Me), 165.50 (CO₂Me). MS: m/z (%) = 377 (10) [M⁺ + 1], 376 (30) [M⁺], 320 (100), 288 (78), 256 (19), 151 (71), 104 (35), 76 (21), 57 (81), 41 (66). Anal. Calcd for C₁₈H₂₀N₂O₇ (376.36): C, 57.44; H, 5.36; N, 7.44. Found: C, 58.00; H, 5.51; N, 7.52.