Aspects of the hydrolysis of formamide: revisitation of the water reaction and determination of the solvent deuterium kinetic isotope effect in base

Abstract

A study of the hydrolysis of formamide is reported with the aims of isolating the water reaction for hydrolysis from the acid and base hydrolysis terms and determining the solvent deuterium kinetic isotope effect (dkie) on base-catalyzed hydrolysis. Respective activation parameters (ΔH‡and ΔS‡) of (17.0 ± 0.4) kcal mol–1and (–18.8 ± 1.3) cal mol–1K–1for the acid reaction and (17.9 ± 0.2) kcal mol–1and (–11.1 ± 0.5) cal mol–1K–1for the base reaction were determined from Eyring plots of the second-order rate constants over the range of 27–120°C. Kinetic studies at the minima of the pH/rate profiles in the pH range from 5.6 to 6.2 in MES buffers at 56°C, and in the pH range of 4.25–6.87 in acetate and phosphate buffers at 120°C are reported. At 56°C the available data fit the expression k56obs= 0.00303[H3O+] + 0.032[HO–] + (3.6 ± 0.1) × 10–9, while at 120°C the data fit k120obs= (0.15 ± 0.02)[H3O+] + (3.20 ± 0.24)[HO–] + (1.09 ± 0.29) × 10–6. Preliminary experimental estimates of Ea(ln A) of 22.5 kcal mol–1(15.03) for the water rate constant (kw) are calculated from an Arrhenius plot of the 56 and 120°C data giving an estimated kwof 1.1 × 10–10s–1(t1/2= 199 years) at 25°C. Solvent dkie values of kOH/kOD= 1.15 and 0.77 ± 0.06 were determined at [OL–] = 0.075 and 1.47 M, respectively. The inverse value is determined under conditions where the the first step of the reaction dominates and is analyzed in terms of a rate-limiting attack of OL–.Key words: formamide, activation parameters, water reaction, acid and base hydrolysis, solvent kinetic isotope effect.