Chapter 8 Enzyme reactions involving imine formation

This chapter discusses the physical organic chemistry of imine formation and the chemical reactivity of the imine adduct thus formed. The formation of iminium ions from basic amines and carbonyl compounds is a two-step process involving addition of the amine to the carbonyl group to form a tetrahedral intermediate, followed by dehydration of this carbinolamine to form the new C–N double bond. At higher pH values, the dehydration of the carbinolamine is the rate-determining step. The rate expression—for example, of the reaction of methyl amine with acetone, is dominated above pH 4 by a term proportional to methyl amine, which reflects rate-determining dehydration of the carbinolamine formed in a rapid pre-equilibrium. The direct observation of this reaction is difficult because of the small equilibrium constant for imine formation. Therefore, this type of reaction is commonly studied by trapping the imine as it is formed with hydroxylamine, which reacts rapidly to form an oxime. Because the equilibrium constant for formation of the imine between methyl amine and acetone is small, the equilibrium is established very rapidly. Thus, the addition of methylamine and acetone to an aqueous solution results in the establishment of an equilibrium concentration of imine (and iminium ion) in several seconds.