Applications of the Vilsmeier reaction in heterocyclic chemistry

3-(2-Chloroethoxy)-1-(4-methoxyphenyl)-1H-pyrazole-4-carbaldehyde

“…Finally, the most downfield 1 H and 13 C NMR signals were easily attributed to the formyl moiety via 1 H- 13 C HSQC and HMBC spectral data (Figure S5). The 15 N NMR data were obtained through the 1 H- 15 N HMBC experiment where the pyrazole 5-H proton (singlet, δ 8.15 ppm) exhibited long-range correlations with neighboring N-1 "pyrrole-like" (δ −179.0 ppm) and N-2 "pyridine-like" (δ −117.0 ppm) nitrogen atoms (Figure S6). 13 C NMR signals were easily attributed to the formyl moiety via 1 H- 13 C HSQC and HMBC spectral data (Figure S5).…”

“…Usually, dimethylformamide and phosphorus trichloride are utilized to form the Vilsmeier reagent [15]. The latter was shown to participate in chlorination as well as chloroformylation reactions [16].…”

Synthesis of novel thiazole, imidazole, benzimidazole, and benzothiazole derivatives incorporating 2‐phenoxy‐N‐arylacetamide unit as novel hybrid molecules

“…Investigations were also conducted on the threecomponent reaction of benzil (27), ammonium acetate, and aldehydes 5a. The single product obtained by the reaction, which was carried out in MeOH at reflux and yielded 78%, was 2-(4-(4,5-diphenyl-1H-imidazol-2-yl) phenoxy)-N-phenylacetamide (28a).…”

“…Figure 1 depicts drugs including thiazole, imidazole, benzimidazole, and benzothiazole, as well as acetamides and phenoxyacetamides. In light of these findings and our ongoing interest in the synthesis of heterocycles with improved pharmacophoric properties [18][19][20][21][22][23][24][25][26][27][28][29][30], we present here the design and synthesis of novel hybrid molecules containing thiazoles, imidazoles, benzimidazoles, and benzothiazoles, each linked to 2-phenoxy-Nphenylacetamide.…”

Acetal Radicals: Synthetic Access and Applications

“…[9,10] Notably, the Vilsmeier-Haack reaction allows for the direct formylation of electron-rich heterocycles and relies on the nucleophilicity of electron-rich arenes for CÀ C bond formation (Scheme 1). [11] Due to the abundance and utility of aldehydes, notably electrophilic heterocyclic aldehydes, the introduction of novel methods and reagents for their installation are required to access a complementary scope of coupling partners (Scheme 1). For the past several decades, radical-mediated reactions have been reported using acetal radicals in lieu of traditionally nucleophilic acyl radicals for coupling with electron-deficient heterocycles.…”