17265-50-8

Upstream product

• 34721-89-6 2-methyl-5-phenyl-furan 
• 100-52-7 benzaldehyde 
• 17265-44-0 (3-methyl-isothiazol-5-yl)-phenyl-methanol 

Relevant academic research and scientific papers

One-step synthesis of 5-acylisothiazoles from furans

Premixed ethyl carbamate, thionyl chloride and pyridine (which generate thiazyl chloride, N≡SCl) in boiling benzene or toluene convert 2,5- and 2,3,5-substituted furans into 5-acylisothiazoles regiospecifically. The reactions are much faster and generally higher yielding in boiling chlorobenzene with more thionyl chloride and with pyridine or isoquinoline as base. Under the more vigorous conditions, even fully substituted 3-bromofurans give isothiazoles, with the displacement of bromine. Deactivated furans, with electron-withdrawing groups such as ester, cyano, benzoyl and phenylsulfonyl in the α-position, react under the more vigorous conditions to give 5-acylisothiazoles with the electronegative group in the 3-position. The 'activated' 2-methyl-5-phenyl- and 5-phenyl-2-phenylthio-furans react analogously, with the more electron-releasing group becoming part of the 5-acyl substituent, exclusively or predominantly. These results are explained by initial electrophilic attack of the furan ring to give a β-thiazyl derivative which spontaneously ring-opens and closes to the isothiazole. The X-ray structures of five of the differently substituted isothiazole compounds are reported. All have very similar patterns of bonding within their isothiazole rings that appear to be independent of the electron-withdrawing or -donating nature of the substituents. Three of the compounds (8a, 8g and 13) have loosely linked chain structures in the solid state, adjacent molecules being connected by combinations of hydrogen bonding and π-π stacking interactions.

Further reactions of furans with trithiazyl trichloride; mechanistic considerations

The reaction of 2,5-diarylfurans with trithiazyl trichloride 1 to give 5-aroyl-3-arylisothiazoles in a useful one-step synthesis of isothiazoles has been extended to both weakly and strongly polarised unsymmetrical 2,5-diarylfurans. These react in an entirely analogous manner; the more electron releasing aryl group becomes incorporated into the 5-aroyl group of the isothiazole as the exclusive (strong polarisation) or the major (weak polarisation) product. However, with 3-bromo-2-(4-methoxyphenyl)-5-(4-nitrophenyl)-furan 7, where the more reactive furan β-position is now substituted, this regiospecificity is reversed (to give isothiazole 8). When one of the α-aryl groups in the furan is replaced by methyl the same regiospecific isothiazole formation is now accompanied by some ring and side chain chlorination (15 → 16 + 17 + 18). All of these results can be explained by mechanisms (Schemes 2 and 5) which involve initial electrophilic attack of the furan to give a β-thiazyl derivative. This highly reactive (nitrenoid) substituent then induces a novel opening of the furan ring 21 to give a highly delocalised intermediate 22 which recyclises to the isothiazole.