Flow 1H nmr study of the rapdid nucleophilic addition of amino acids to 4-formylpyridine

Article abstract of DOI:10.1139/v82-113

Rapid addition of primary amino acids and imidazole to 4-formylpyridine to form carbinolamine intermediates in water has been studied by means of stopped-flow ¹H nuclear magnetic resonance spectroscopy.The equilibrium constant K_n for this process was determined using stopped-flow uv spectroscopy.For the amino acid D,L-alanine and its derivatives , D,L-alanine methyl ester and D,L-alanylglycine K_n does not appear to correlate with K_a, the acid dissociation constant.Values of k_n, the addition rate constant, appear to be independent of pH and bufferconcentration fo these nucleophiles.The limited data indicate that the variation in rates of nucleophilic addition to 4-formylpyridine cannot be accounted for in terms of pK_a, K_n or related to systematic changes in structure of the nucleophile.As a group, the primary amino acid D,L-alanine and its derivatives have comparable k_n values within a factor of two in spite of their different pK_a values.Imidazole, an aromatic secondary diamine, has a k_n value that is 10 to 20 times larger than these primary amines and has a relatively small K_n value.At the same time , its k_n value is comparable to that found previously for sarcosine, a secondary acyclic amino acid having substantially larger pK_a and K_n values.The nucleophilic addition step of primary amino acid and derivatives is rapid relative to the subsequent dehydration and prototropic shift steps.It occurs in a pH range at which pyridine nitrogen protonation is negligible.