WATER SOLVENT EXCHANGE-RATES OF PRIMARY AMIDES - ACID-CATALYZED NMR SATURATION TRANSFER AS AN INDICATOR OF ROTATION AND STRUCTURE OF THE PROTONATED FORM

The nitrogen proton resonances of several primary amides have been studied by Fourier transform NMR. The generally accepted assignment of these resonances has been confirmed by nuclear Overhauser effect. Solvent exchange rates have been measured for the amide protons of propionamide, α and β-chloropropionamide, oxidized and reduced nicotinamide adenine dinucleotide, and benzamide by means of pulsed NMR saturation recovery and solvent saturation transfer, and roughly estimated for other compounds by NMR saturation. Base catalysis of exchange for the proton cis to the carbonyl oxygen is roughly twice that previously observed for analogous N-methylamides. Base catalysis for the proton trans to the carbonyl oxygen is roughly three times more rapid than for the cis proton. Acid catalysis rates are the same for cis and trans protons for all saturated amides, and are roughly ten times faster than has been reported for analogous N-methylamides. Rotation of the amide nitrogen has been estimated by means of saturation transfer between cis and trans resonances. There is a pH-independent rotation at a rate of roughly 1 s-1 at 22°C, and no base-catalyzed rotation. There is definite acid-catalyzed rotation resulting in 20-40% saturation transfer for saturated amides at low pH. These data are interpreted in terms of N-protonation and rotational diffusion of the protonated form at a rate comparable to deprotonation, for the saturated amides. There is asymmetric saturation transfer for unsaturated compounds; the acid-catalyzed trans to cis saturation transfer is 75% for benzamide and methacrylamide, but much smaller from cis to trans. In these compounds the trans proton shows more rapid solvent exchange than the cis proton. The kinetic behavior for the unsaturated amides is generally consistent with the model of Perrin, but the strong trans-cis saturation transfer indicates the existence of some other, unknown, acid-catalyzed rotation mechanism not involving nitrogen protonation. © 1979, American Chemical Society. All rights reserved.