Ketone to enamine equilibrium constants

Important parameters for understanding the efficiency of primary amine catalysis are the ketone + amine to enamine equilibrium constants. Unfortunately, data are very scarce. Equilibrium constants for the interconversion (65) of [2H6]acetone and protonated enamine in water ( H = 

Recently, the present author (Toullec and Verny-Doussin, 1980) obtained a concordant value for the equilibrium constant of (65 L = H) for [83, n — 3] from kinetic data on amine-catalysed iodination of acetone at low iodine concentrations. The principle of this determination is similar to that described for estimation of the keto-enol equilibrium constants by the kinetic halogenation method (see p. 48). At low iodine concentrations ( 10-6 mol dm-3), the enamine pathway is preferred [see (61)] and iodination of the enamine is rate-limiting. Rate measurements, in a pH range in which only the monoprotonated and diprotonated forms of the diamine exist, made it possible to determine the second-order rate constants k u which include the equilibrium constants, for interconversion of the ketone and protonated enamine 

It is of great interest to compare this last value with the keto-enol equilibrium constant obtained similarly for acetone = 0.35 x 10-8). Indeed, in many enzyme-catalysed reactions, aldolisation for example, enamine formation is not rate-limiting, and the rate is usually controlled by subsequent electrophilic additions. Consequently, the rate depends on enamine reactivity and on the enamine concentration at equilibrium. Therefore, if one wants to compare the two processes, via enol and via enamine, in order to explain why the enamine route is usually preferred, the difference in equilibrium constants for enol and enamine formation must be taken into account. Data on ketone to enol and ketone to enamine equilibrium constants show that the enamine and enol concentrations are of similar magnitude even for relatively small concentrations of primary amine. Thereafter, since the enamine is much more reactive than the enol for reactions with electrophilic reagents (in a ratio of 4-6 powers of ten for proton addition), it can be easily understood why the amine-catalysed pathway is energetically more favourable. 

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