Chemistry of Polyhalogenated Nitrobutadienes, Part 11: ipso-Formylation of 2-Chlorothiophenes under Vilsmeier-Haack Conditions

Abstract

The regioselective ipso-formylation of electron-rich, 3,4-push-pull-substituted 2-chlorothiophenes under Vilsmeier-Haack conditions was performed in good yields. The synthetic scope of this new reaction was explored using various halothiophenes, chloroanilines, and 1-methyl-3-chloroindole. In comparison with their structural C-H analogs the chlorinated thiophenes, anilines, and the indole proved to be less reactive toward electrophilic attack by chloromethyleniminium salts.

Polyhalonitrobutadienes as Versatile Building Blocks for the Biotargeted Synthesis of Substituted N-Heterocyclic Compounds

“…The push-pull substituted thiophene 53 was efficiently accessible in 85% yield upon treatment of dithiolane 52 with sodium hydroxide using DMSO as solvent. The regioselective ipso-formylation of the 2-chloro-thiophene 53 under Vilsmeier-Haack conditions led to the carbaldehyde 54 (64% yield), according to [82].…”

“…The next successive steps were performed with the most stable derivative 3-morpholino-4-nitro-5-(vinylthio)thiophene-2-carbaldehyde (55) [82]. Knoevenagel condensation of thiophene 55 with malononitrile in ethanol in the presence of a catalytic amount of sodium ethanolate gave the gem-dicyanovinylthiophene 56 in 68% yield [83].…”

Formation of Carbon-Silicon Bond and Effect of Silicon on Organic Reactions

“…For formylation of thiophene, Vilsmeier reaction is well known for the formulation of thiophene (Vogt et al, 2012;Su et al, 2010). Vilsmeier reaction has been performed which form comparatively weak electrophile (Scheme 1).…”

SO2ClF-promoted chlorination-oxidation of 2-methylindoles: a one-step synthetic method to access 2,3-difunctionalized indoles

“…Following a similar route, the Kaufmann group reported that the formylation process using the Vilsmeier reagent instead could also give the desired product, however, with a low yield of only 30% (Scheme 1b, condition B). 10 Jiang et al recently introduced a facile method that relies on the chlorination-oxidation of 2-indolylmethanols in the presence of 1,3-dichloro-5,5-dimethylhydantoin (DCDMH) (Scheme 1b). 11 However, this approach requires the preparation of alcohol as the starting material.…”