Protonation of Amides

Evidence from cryoscopic measurements is presented that N,N-dimethylformamide (DMF), N,N-dimethylacetamide (DMA), N-methylacetamide (NIMA) and acetamide are monoprotonated in 100% sulfuric acid. The n.m.r. spectra of a wide variety of amides in acid solution have been investigated. It is concluded that all materials examined protonate predominantly on oxygen. In aqueous acid solution proton exchange on nitrogen has been detected, the concentration of N-protonated species being too small to measure. A more precise method for calculating barriers to rotation for DMF is described and the values found for pure DMF and protonated DMF are 9.6 +/- 1.5 and 12.7 +/- 1.5 kcal./mole, respectively. The rate of exchange protolysis on nitrogen of DMA is first order in (DMA) and (H+) with a rate constant of 400 M-1 sec.(-1). The activation energy for this process for 0.4 M DMA in 6 M aqueous HCl is 7 +/- 0.5 kcal./mole.