Base-promoted Ionisation

It is generally considered that the kA. [Afl terms in the general rate law (3) correspond to rate-limiting base-promoted ionisation leading to enolate (4). 

Extensive studies were devoted to verifying the Bronsted equation (5) when Aj- is varied. Linear relationships with the slope depending on the ketone were 

Modern theoretical developments in the theory of proton-transfer reactions suggest that such linear Bronsted plots are only a first approximation when the range of the P-KHA-values is narrow. When a wider range of bases is used, the curve obtained should be such that the Gibbs free energy of activation AG fits the Marcus eqn (6). This equation was derived (Cohen and Marcus, 1968  

Marcus, 1969) by assuming that the point which represents the transition state on the potential energy profile is the intersection of two parabolas of equal curvature. It was also considered that the proton abstraction reaction can be divided up [eqn (7)] into three discrete steps (0 encounter of the reactants, (ii) 

Attempts were made to observe a curvature of the Bronsted plots for ketone ionisation. Cohen and Marcus (1968) and Bell (1973) (see also J. R. Jones, 1973 Kresge, 1975b) collected data for the reaction of carbonyl compounds (including ketones, esters and keto-esters) with bases and have observed a slight curvature. The data fit the Marcus equation with AG% = 10 kcal mol-1 and Wr = 4 kcal mol-1 (Hupe and Wu, 1977). 

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Substituent effects on rate constants of base-promoted ionisation of ketones have led to the conclusion that an electron-withdrawing substituent increases the rate of ionisation, in agreement with the anionic character of the transition state. This is based chiefly on studies on halogenation and isotope exchange of aromatic ketones. Data on p-values observed by plotting ionisation rate constants versus Hammett -parameters (Table 3) for substituted... 

A great number of data on inductive effects in the aliphatic series have been reported. Broadly speaking, results are in agreement with what is expected from the anionic and cationic characters of the transition states an electron-withdrawing substituent increases the rate of the base-promoted ionisation, whereas it retards that of acid-catalysed enolisation. For instance, a bromine atom at the exposition modifies the rate constants of acetate and HCl-catalysed bromination of acetone in water by factors of 4400 and 1/6.5, respectively (R. A. Cox and Warkentin, 1972 Watson and Yates, 1932). 

Deprotonation trans to the leaving group is especially effective at promoting the dissociation step. The conjugate base mechanism cannot operate if a tertiary amine with no ionisable proton is placed trans to the leaving group as expected the rate of substitution is then slower and does not depend on [OH-]. 

The pH of the buffer used in the mobile phase will affect the EOF. In most silica reversed-phase-based packing, the silanol groups on the surface of the phase will only be ionised at higher pHs (> 4). The recent intrcxluction of Mixed Mtxle phases [24) incorporating SCX groups and C, s or Q alkyl chains attached to each particle surface has allowed the use of low-pH buffers, as the SCX groups are ionised and promote stable EOF over a wider pH range. This is discussed in the next section. 

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