Vilsmeier-Haack reagent-promoted formyloxylation of alpha-chloro-N-arylacetamides by formamide

In this study, a Vilsmeier-Haack reagent-promoted formyloxylation of alpha-chloro-N-arylacetamides by formamide was developed. The reaction successfully provided the desired alpha-formyloxy-N-arylacetamides 4 and 7a-n in moderate to excellent yields (70-96%) by use of 3.0 equivalents of PBr3 at 80-90 degrees C and was applicable to substrates bearing electron-donating or withdrawing groups at the aryl moiety. For alpha-chloro-N-(naphthalenyl)acetamide (8a), alpha-chloro-N-(quinolin-8-yl)acetamide (8b), and alpha-chloro-N-(thiazol-2-yl)acetamide (8c) possessing the alpha-chloro group, the reaction also provided the desired formyloxylated products 9a-c in 70-87% yields. A plausible mechanism was proposed through the activation of alpha-chloroacetamide by the Vilsmeier-Haack reagent to account for the new transformation.