Formamide Hydrolysis in Alkaline Aqueous Solution: Insight from Ab Initio Metadynamics Calculations

摘要

The nucleophilic attack of an amide bond by hydroxide is probably one of the best illustrations of solvent effects in chemistry (see Scheme 1).While barrierless and highly exothermic in the gas phase,formation of the tetrahedral intermediate (TI) is the rate-determining step in the hydrolysis of formamide in alkaline aqueous solution,with a free energy of activation of about 21 kcal mol~(-1).