Nitrogen-15 nuclear magnetic resonance spectroscopy. N?H proton exchange reactions of urea and substituted ureas

Proton-coupled nitrogen-15 NMR spectra of urea, N-methylurea, N,-N′-dimethylurea, N-methyl-N′-benzylurea and N-phenylurea have been obtained at natural abundance level in neutral, basic and acidic solutions at 25°C. Base-catalyzed N? H proton exchange of the ? NH₂ group of N-methylurea in water was found to be 1.5 times faster than that for the -NH- group, while the corresponding acid-catalyzed exchange is 7.5 times faster. Comparison of urea and N,-N′-dimethylurea in water shows urea to be 10 times faster in base but 2 times slower in acid. The ratio of the base-catalyzed N? H proton exchanges of the two -NH- groups of N-methyl-N′-benzylurea in dimethyl sulfoxide is close to unity, whereas the CH₃NH- group exchanges 4 times faster in acid. Similarly, the C₆H₅NH- group of N-methyl-N′-phenylurea exchanges 50 times faster than the CH₃NH- group in base and about 3 orders of magnitude slower in acid. The results are rationalized by consideration of steric and electronic effects.