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

Ruipeng Bao; Yao Wang; Xinbo Lin; Jinglin Tan; Zhihua Chen; Teng Wang; Xinhong Yu

doi:10.1055/s-0043-1775412

Synlett, Table of Contents

Synlett 2025; 36(07): 841-844
DOI: 10.1055/s-0043-1775412

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

Ruipeng Bao

^aEngineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, and State Key Laboratory of Bioengineering Reactors, East China University of Science and Technology, Shanghai 200237, P. R. of China

,

Yao Wang

^aEngineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, and State Key Laboratory of Bioengineering Reactors, East China University of Science and Technology, Shanghai 200237, P. R. of China

,

Xinbo Lin

^aEngineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, and State Key Laboratory of Bioengineering Reactors, East China University of Science and Technology, Shanghai 200237, P. R. of China

,

Jinglin Tan

^aEngineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, and State Key Laboratory of Bioengineering Reactors, East China University of Science and Technology, Shanghai 200237, P. R. of China

,

Zhihua Chen∗

^bShanghai Aoqi Pharmaceutical Co., Shanghai, P. R. of China

,

Teng Wang∗

^cCollege of Chemical Engineering, Beijing Institute of Petrochemical Technology, Beijing 102617, P. R. of China

,

Xinhong Yu ∗

^aEngineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, Shanghai Key Laboratory of New Drug Design, School of Pharmacy, and State Key Laboratory of Bioengineering Reactors, East China University of Science and Technology, Shanghai 200237, P. R. of China

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Abstract

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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

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References

References and Notes
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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.

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