Protonation pre-equilibrium

The influence of / ara-substituents on the benzamide and benzyloxyl side chains upon the pre-equilibrium protonation step is likely to be negligible considering their remoteness from the site of protonation and their electronic influence must rather impact upon the rate determining N-O bond heterolysis step. Para-substituents on the leaving group should impact upon both the protonation and bond heterolysis steps. 

A mechanistic study of acid and metal ion (Ni2+, Cu2+, Zn2+) promoted hydrolysis of [N-(2-carboxyphenyl)iminodiacetate](picolinato)chromate (III) indicated parallel H+- or M2+-dependent and -independent pathways. Solvent isotope effects indicate that the H+-dependent path involves rapid pre-equilibrium protonation followed by rate-limiting ring opening. Similarly, the M2+-dependent path involves rate-determining Cr-0 bond breaking in a rapidly formed binuclear intermediate. The relative catalytic efficiencies of the three metal ions reflect the Irving-Williams stability order (88). 

Hydride transfer from [(bipy)2(CO)RuH]+ occurs in the hydrogenation of acetone when the reaction is carried out in buffered aqueous solutions (Eq. (21)) [39]. The kinetics of the reaction showed that it was a first-order in [(bipy)2(CO)RuH]+ and also first-order in acetone. The reaction proceeds faster at lower pH. The proposed mechanism involved general acid catalysis, with a fast pre-equilibrium protonation of the ketone followed by hydride transfer from [(biPy)2(CO)RuH]+. 

The kinetics of the ionic hydrogenation of isobutyraldehyde were studied using [CpMo(CO)3H] as the hydride and CF3C02H as the acid [41]. The apparent rate decreases as the reaction proceeds, since the acid is consumed. However, when the acidity is held constant by a buffered solution in the presence of excess metal hydride, the reaction is first-order in acid. The reaction is also first-order in metal hydride concentration. A mechanism consistent with these kinetics results is shown in Scheme 7.8. Pre-equilibrium protonation of the aldehyde is followed by rate-determining hydride transfer. 

Prior to 1967 acetal hydrolysis had been found to be a specific-acid catalysed reaction with the accepted mechanism [equation (46)] involving fast pre-equilibrium protonation of the acetal by hydronium ion, followed by unimolecular rate-determining decomposition of the protonated intermediate to an alcohol and a resonance stabilized carbonium ion (Cordes, 1967). An A-1 mechanism was supported by an extremely large body of evidence, but it appeared unlikely that such a mechanism could expledn the... 

Ru Ru step and a self-exchange rate of 2xlO" M s for the c -[Ru 0)2(L)] " /cw [Ru (0)2(L)]+ couple has been estimated a mechanism involving a pre-equilibrium protonation of ci5-[Ru (0)2(L)]+ followed by outer-sphere electron transfer is proposed for the Ru Ru step. For reduction by [Fe(H20)6] +, an outer-sphere mechanism is proposed for the first step and an inner-sphere mechanism is proposed for the second step. ... 

A series of A-benzoyloxy-A-benzyloxybenzamides (116) reacted with similarly positive AS (25-29 calK moH ) but with lower a values of between 11 and 21 kcal mol . Rate constants at 308 K gave a positive Hammett a correlation but with a much smaller /O-value of 0.32 in accordance with the opposing influences of para substituents, Z, on the pre-equilibrium protonation and heterolysis steps . ... 

The available studies imply that general catalysis will be operative in systems involving sulfate monoesters and potential six-membered ring transition states. Salicyl sulfate hydrolyzes at pH 4 via intramolecular carboxyl group participation involving pre-equilibrium proton transfer leading to sulfur trioxide expulsion (Fig. 9)2HH, viz. 

If it is assumed that ester hydrolysis by the AAc2 mechanism involves fast pre-equilibrium protonation of the substrate, followed by rate-determining attack of water on the conjugate acid of the ester, the mechanism can be written as... 

We see here that the mechanism with a pre-equilibrium proton transfer leads to a specific acid catalysis rate law whereas that with a rate-determining proton transfer leads to general acid catalysis. It follows that, according to which catalytic rate law is observed, one of these two mechanisms maybe excluded from further consideration. Occasionally, however, different mechanisms lead to the same rate law and are described as kinetically equivalent (see Chapters 4 and 11) and cannot be distinguished quite so easily. 

In examples such as the above, the rate law establishes the composition of the activated complex (transition structure), but not its structure, i.e. not the atom connectivity, and provides no information about the sequence of events leading to its formation. Thus, the rate law of Equation 1.2 (if observed) for the reaction of Equation 1.1 tells us that the activated complex comprises the atoms of one molecule each of B and X, plus a proton and an indeterminate number of solvent (water) molecules, but it says nothing about how the atoms are bonded together. For example, if B and X both have basic and electrophilic sites, another mechanistic possibility includes a pre-equilibrium proton transfer from AH to B followed by the reaction between HB+ and X, and this also leads to the rate law of Equation 1.2. Observation of this rate law, therefore, allows transition structures in which the proton is bonded to a basic site in either B or X, and distinguishing between the kinetically equivalent mechanisms requires evidence additional to the rate law. 

For rate-determining proton transfer (mechanism A-SK2), the determined AV value directly refers to the slow step. For the mechanisms with pre-equilibrium proton transfer, A1 and A2, the experimental AV is the sum of the volume changes of the two steps... 

Consequently, the expected kinetic solvent isotope effect in the case of pre-equilibrium proton transfer [2, 97, 99] is... 

It may be concluded that rate-determining proton transfer in the first step (mechanism A-Se2) is indicated if kH/kD > 1 [2, 4, 99]. On the other hand, pre-equilibrium proton transfer (mechanisms A1 or A2) is indicated if kH/kD < 0.6. 

A distinction between mechanisms A1 and A2 on the basis of solvent isotope effect data is probably feasible if model calculations [102] of isotope effects are carried out with special consideration of the particularities of the reaction under study. In a similar way, it may be possible to distinguish between rate-determining and pre-equilibrium proton transfer with the aid of model calculations for reactions with kH/kD values in the region around 0.7 to 0.9. 

When a base catalyzed reaction with proton transfer in the first step is carried out in D20 solution, the substrate exchanges its acidic hydrogen with the deuterium of the solvent before the reaction takes place if the mechanism is fast pre-equilibrium proton transfer with subsequent slow step. If, on the other hand, hydrogen exchange does not occur prior to the reaction, it may be concluded that proton transfer is the rate-determining step. 

The solvent isotope effect for the acid catalyzed hydrolysis of ethyl diazoacetate (without halide ions) is much smaller than 1 (Table 19, p. 63) as expected for a pre-equilibrium proton transfer mechanism. Furthermore, according to the findings of Roberts et al. [205] the products of ethanolysis of ethyl diazoacetate in C2HsOD solution are C2HS OCHDCOOEt as well as C2 H5 OCD2 COOEt which indicates that H exchange is faster than ethanolysis. 

The solvent isotope effects on individual rate coefficients computed from the experimental results are fe /fep = 2.32, kfJ°/kf2° = 3.68, kf fe jfe5i/fep fe fe i = 0.28. The first two values are of the magnitude expected for rate-determining proton transfer. The third quantity corresponds to a solvent isotope effect on a reaction with pre-equilibrium proton transfer, and the value is of the expected magnitude. It is approximately equal to Ks D /Ks H since fen % /eft. 

The halogenation of ketones is also general acid catalysed. The mechanism usually consists of a rapid pre-equilibrium protonation of the carbonyl group followed by a slow proton transfer from carbon to the base catalyst [41]. The enol thus produced reacts rapidly with halogen. The overall mechanism is similar to mechanism (7) described earlier and the observed rate coefficient is a product of the equilibrium constant for protonation of the carbonyl group and the rate coefficient for the proton transfer from carbon, and therefore does not refer to a single proton transfer step. 

Differences in Structure - Reactivity Patterns in Acid-catalysed and Spontaneous Hydrolyses - Effect of the Pre-equilibrium Protonation... 

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