Synthesis of primary aromatic amides by aminocarbonylation of aryl halidesusing formamide as an ammonia synthon

Primary aromatic amides were prepared by a palladium-catalyzed aminocarbony lation reaction of aryl halides in high yields (70-90%) using formamide as the amine source. The reactions require a palladium catalyst in combination with a nucleophilic Lewis base such as imidazole or 4-(dimethylamino)pyrid ine (DMAP). Aryl, heteroaryl, and vinyl bromides and chlorides were convert ed to the primary amides under mild conditions (5 bar, 120 degreesC) using 1 mol % of a palladium-phosphine complex. Best results were obtained in dio xane using triphenylphosphine as the ligand and DMAP as the base. For activ ated aryl bromides, a phosphine-to-palladium ratio of 2:1 was sufficient, b ut less reactive aryl bromides or aryl chlorides required ligand-to-palladi um ratios up to 8:1 in order to stabilize the catalyst and achieve full con version. The influence of catalyst, base, solvent, pressure, and temperatur e was studied in detail. The mechanism of the reaction could be clarified b y isolating and identifying the reaction intermediates. In addition, methyl amides and dimethylamides were prepared by the same method using N-methylfo rmamide and N,N-dimethylformamide as the amine source.