A Consecutive Four‐Component Synthesis of Polysubstituted Thiophenes in Aqueous Medium

Abstract

An efficient and straightforward four‐component synthesis of mono‐, bi‐ and tricyclic thiophenes from C–C + C + C + S atom fragments from 1,3‐dicarbonyl compounds, aldehydes, activated methylene halides and elemental sulfur in aqueous medium is described. Arylidene‐1,3‐dicarbonyls, N‐phenacylpyridinium bromides/N‐(p‐nitrobenzyl)pyridinium chloride, pyridinium ylides and 2,3‐dihydrofurans are believed to be the key intermediates of these consecutive transformations. This synthetic strategy provides a potential route to the construction of a library of highly substituted thiophenes with a large substrate scope in good‐to‐excellent yields.

Recent Advances in the Synthesis of Heterocycles via Reactions Involving Elemental Sulfur

“…hyde 12 and α-pyridiniumacetophenone bromide 14 (generated from reaction between phenacyl bromide 13 and pyridine). [5] Likewise, 1,3-diketo compounds such as 4-hydroxycoumarine, ethyl acetoacetate, dimedone and cyclohexa-1,3-dione could be used in place of penta-2,4dione, whereas p-nitrobenzyl chloride displayed the same reactivity in this kind of multicomponent reactions. Selected examples were shown in Scheme 5.…”

“…While the reaction conditions were relatively complex with the involvement of copper-TEMPO-2,2'-bipyridine catalysts and tetrabutylammonium acetate as an ionic reaction medium, the reaction followed the same pathway as for the reaction of o-nitrochalcones with sulfur in the presence of a tertiary amine previously described by our group (Section 2.2.1). [16,17] Huang et al reported a copper-catalyzed threecomponent access to a variety of benzo [4,5]thieno [3,2c]isoquinoline and thieno[3,2-c]isoquinoline 105 from methylketoxime acetates 103, o-halobenzaldehydes 104, and elemental sulfur (Scheme 39). [39] It was postulated that 3-aminobenzothiophene would be formed from sulfuration of acetophenone oxime acetate.…”

“…According to the proposed reaction pathway, it is possible that 2-aminobenzothiophene 125 displays similar behavior (Scheme 46). [52] Generated in situ from o-bromophenylacetonitriles 122 by copper-catalyzed sulfuration with elemental sulfur, this heteroaromatic amine could be further sulfuration and trapped with a benzadehyde to provide 2-phenylbenzo [4,5] thieno[2,3-d]thiazole 124.…”

One-Pot Synthesis of 2,4-Diacyl Thiophenes from α-Oxo Ketene Dithioacetals and Propargylic Alcohols

“… The traditional approach to obtaining 2-acylthiophenes relies on late-stage modification via the Friedel–Crafts acylation of thiophenes using specific Lewis acid promoters combined with acyl anhydrides or acid chlorides, which often provides poor atom economy and/or deleterious environmental effects . However, the synthesis of 2-acylthiophenes has received little attention and, to the best of our knowledge, there have been no reports to date concerning the straightforward synthesis of 2,4-diacylthiophenes from alkynes …”

l-Proline-Catalyzed Three-Component Reaction of 4-Chloro-3-formylcoumarin, Sodium Sulfide, and α-Halo Ketones: A Direct Approach to Thieno[3,2-c]coumarins

“…Utilizing the first approach, thieno[3,2-c]coumarins were synthesized by four-component reaction of 4-hydroxycoumarin, phenacyl bromides, aromatic aldehydes and elemental sulfur. The reaction was mediated by pyridine and involved the use of both trimethylamine and morpholine as catalysts 40 . Moreover, thieno[3,2-c]coumarins were prepared by the reaction of chalcones, 4-hydroxycoumarin and elemental sulfur.…”