Synthesis of primary amides by a one-pot reaction of ammonia gas with esters or tertiary amides

Relative to secondary or tertiary amides, the synthesis of primary amides is more challenging because only a few nitrogen sources, such as NH 3 , NH 2 − , and others, can be used in these synthetic methods. Here, we present an efficient and rapid method for the synthesis of primary amides by a one-pot reaction of NH 3 gas and unactivated esters at ambient temperature, in which sodium hexamethyldisilazide was used to initiate the reaction by abstracting a proton of NH 3 . The reaction had a broad substrate scope tolerating sensitive substituents and was also used to synthesize bioactive molecules and 15 N-labeled drugs from 15 NH 3 gas. Furthermore, this strategy is also appropriate for the transamidation of various tertiary amides and amidation of phosphinate esters. The mechanism revealed that the NaNH 2 forming in situ is a crucial species in the reaction. This work provides an alternative method for amidation and transamidation by directly using gaseous NH 3 .