Equilibria for the reaction of amines with formaldehyde and protons in aqueous solution. A re-examination of the formol titration.

The existence of protonated hydroxymethylamines of sec+ ondary amines, RzNHCHtOH, in equilibrium with hydroxymethylamines and protonated amines, has been demonstrated by titration at equilibrium and by rapid titration of the protonated hydroxymethylamines. Analogous compounds, . R3NCHeOH, are formed from formaldehyde and the sterically favorable tertiary amines: pyridine, iv-methylimidazole, and triethylenediamine. The equilibrium constants for the formation of these cationic hydroxymethylamines are two to three orders of magnitude less favorable than for the formation of neutral hydroxymethylamines; conversely, the basicity of hydroxymethylamines is two to three orders of magnitude less than that of the parent amines. These differences are ascribed primarily to solvation and polar effects. Protonation of the dihydroxymethyl adducts of primary amines was not detected. An analysis of the complex equilibria for the addition of protons and hydroxymethyl groups to imidazole suggests that protonation and hydroxymethylation do not occur on the same nitrogen atom. The equilibrium constant