One-Pot Three-Component Access to Furan and Thiophene Derivatives

Abstract

The furan and thiophene skeleton structures are widely present in natural products and synthetic drugs, and display multiple bioactivities. An effective one-pot three-component reaction to access furan and thiophene derivatives from 2-bromo-5-(dichloromethyl)furan or -thiophene; cyanoacetate esters, cyanoacetamides, or malononitrile; and aliphatic secondary amines has been developed. The multicomponent reaction for the construction of new C–N and C–C bonds in one pot is simple, mild, and efficient, and the yield of the target product is as high as 96%.

Key words

one-pot reaction - multicomponent reaction - furans - thiophenes - cascade reaction

Publikationsverlauf

Eingereicht: 03. August 2024

Angenommen nach Revision: 18. September 2024

Artikel online veröffentlicht:
25. November 2024

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• 14 Compounds 4a–z; General Procedure A round-bottomed flask was charged with the appropriate compound 1 (1.0 mmol) and EtOH (10 mL), and the mixture was stirred at r.t. until 1 dissolved. The appropriate compounds 2 (1 mmol) and 3 (1 mmol), Et₃N (3 equiv), and EtOH (10 mL) were added, and the mixture was refluxed until the reaction was complete (TLC). The mixture was then concentrated under vacuum, and the crude product was purified by column chromatography (silica gel). Ethyl (2E)-2-Cyano-3-(5-morpholin-4-yl-2-furyl)acrylate (4a) Pale-yellow solid; yield: 84%. ¹H NMR (400 MHz, CDCl₃): δ = 7.53 (s, 1 H), 7.06 (s, 1 H), 5.46 (s, 1 H), 4.29 (q, J = 7.1 Hz, 2 H), 3.84–3.80 (m, 4 H), 3.54–3.49 (m, 4 H), 1.34 (t, J = 7.1 Hz, 1 H). ¹³C NMR (100 MHz, DMSO-d ₆): δ = 165.1, 164.1, 140.1, 135.5, 133.7, 118.8, 92.6, 81.6, 65.7, 61.0, 46.0, 14.8. HRMS (EI): m/z [M⁺] calcd for C₁₄H₁₆N₂O₄: 276.1110; found: 276.1111.