Insights into the triple self-condensation reaction of thiophene-based methyl ketones and related compounds

Abstract

The acid catalysed triple self-condensation of 1-thien-2-ylethanone (2-acetylthiophene) and five related compounds is presented. Tetrachlorosilane used as the Lewis acid produces dry hydrogen chloride which catalyzes the self-condensation process. Depending on the reaction conditions and the substitution of the carbonyl substrates, the reaction can proceed as a [2+2+2] cyclotrimerization towards C 3 -symmetric 1,3,5trisubstituted benzenes, or as the single-type aldol condensation leading to 1,3-disubstituted (E)-β-methylchalcones. This is important for the design of new aromatic/olefinic compounds beyond the model structures. Synthesis of 4'-fluoro-3,5-di-(2-thienyl)biphenyl through a mixed-type aldol reaction using erbium triflate is discussed. Mechanistic rationale is provided.

2-{3,5-Bis-[5-(3,4-didodecyloxyphenyl)thien-2-yl]phenyl}-5-(3,4-didodecyloxyphenyl)thiophene

“…Though this method is applicable to acetylthiophene [27], the cyclization of the analogous 5-bromo-2-acetylthiophene failed [28]. Nevertheless, Tokárová reported a 28% yield of the trimer when SiCl 4 /ethanol was used as dehydrating agent [29]. In an extensive study, we could raise the yield up to 37%.…”