Rate-determining protonation

The kinetic features of this reaction, including the solvent isotope effect, are consistent with a rate-determining protonation to form a vinyl cation. ... 

In agreement with expectation for a rate-determining proton transfer, the reaction shows general acid catalysis. Base-catalyzed ketonization occurs by C-protonation of the enolate. 

Reversible electron addition to the enone forms the radical anion. Rate determining protonation of the radical anion occurs on oxygen to afford an allylic free radical [Eq. (4b) which undergoes rapid reduction to an allylic carbanion [Eq. (4c)]. Rapid protonation of this ion is followed by proton removal from the oxygen of the neutral enol to afford the enolate ion [Eq. (4c)]. 

The reaction is general acid, not specific acid catalyzed, implying rate-determining proton transfer from the acid to the double bond. " ... 

This is ordinary electrophilic addition, with rate-determining protonation as the first... 

The general acid catalysis, the deuterium solvent isotope effects, and the lack of deuterium incorporation upon partial hydration in D2 0 are particularly convincing evidence for a rate-determining protonation and the discrete intermediacy of a vinyl cation such as 6. 

Clearly, a large body of diverse evidence indicates that the acid-catalyzed hydration of alkynyl ethers and thioethers proceeds via a rate-determining protonation through a vinyl cation. However, these vinyl cations are unique in that they have a resonance form where the positive charge resides on the... 

Rate-determining protonation to give a vinyl cation rather than 1,4 addition of water has been proposed as the most consistent mechanism (25) for the acid-catalyzed hydration of arylpropiolic acids in aqueous sulfuric acid. Hydration of arylpropiolic acid closely resembles the acid-catalyzed isomeriza-... 

In contrast, the hydration of arylbenzoylacetylenes is believed to proceed via a vinyl cation formed by rate-determining protonation on carbon (28) ... 

However, the observations of Ward and Sherman need not rule out triple-bond participation and vinyl cations in the systems studied by Hanack and co-workers (75-79). Presumably, the enol formate 61 itself arises via a transition state involving a rate-determining protonation and vinyl cation 62 (see previous section). A vinyl cation such as 62 with an adjacent phenyl group is considerably more stable and hence more accessible than a vinyl cation such as 63, stabilized only by a neighboring alkyl group. Hence, formation of enol formate 61 and its... 

This involves rate-determining proton transfer, equation (37) in principle it should show general acid catalysis, but in practice this usually cannot be seen as the catalyzing acid is simply H30+ . A typical example would be aromatic hydrogen exchange, such as the detritiation of tritiated benzene shown in equation (38) 147... 

The observation of a primary solvent deuterium isotope effect (kH/fa>) = 2-4 on the specific acid-catalyzed hydrolysis of vinyl ethers provides evidence for reaction by rate-determining protonation of the alkene.69 Values of kHikD 1 are expected if alkene hydration proceeds by rate-determining addition of solvent to an oxocarbenium ion intermediate, since there is no motion of a solvent hydron at the transition state for this step. However, in the latter case, determination of the solvent isotope effect on the reaction of the fully protonated substrate is complicated by the competing exchange of deuterium from solvent into substrate (see above). 

Another way in which a transition-metal hydride may conceivably interact with a substrate is by rate-determining proton transfer to the substrate itself, reaction 7. 

The radical anion pathway (e-c-P-d-p Scheme 2) requires a rate-determining protonation after cyclization, i.e., a slow protonation of a hard oxyanion. However, such proton transfer rates are usually diffusion controlled, so this seems unlikely [32,33], On the other hand, the carbanion closure (e-P-d-c-p) portrayed in Scheme 4 requires a very reasonable suggestion that the ratedetermining step corresponds to protonation of the soft, weakly basic radical anion 42, prior to cyclization [32-35] this is the preferred mechanism. One must use caution, however, realizing that these conclusions are drawn for the particular set of substrates which were examined. In some cases, radical anion cyclization remains a viable option. 

A further investigation of the ortholithiation of anisole has taken advantage of previous spectroscopic evidence of the exclusive formation of disolvated dimers of n-BuLi in TMEDA, combined with rate studies which demonstrate that this combination promotes ortholithiation via [(n-BuLi)2((TMEDA)2(anisole)] in pentane. The substantial kinetic isotope effect fcbs(H)/ obs(D) = 20 3] found on comparison of anisole with anisole- fg is indicative of rate-determining proton transfer but the unusually high value has not been explained satisfactorily. 

The loss of optical activity accompanying deprotonation of (/f)-2,2,6-trimethyl-cyclohexanone by lithium diisopropylamide (LDA, which exists as a dimer) in THF is governed by the rate equation v = /c [ketone] [LDA]°-, which is consistent with a rate-determining proton transfer involving amine monomer. ... 

The nitrosation of A-alkylureas in dioxane-acetic acid mixtures is governed by the expression v = fc[HN02][urea], at fixed pH, and dependent on rate-determining proton transfer from the protonated iV-alkyl-iV-nitrosourea to acetate anion the order of reactivity, which reflects relative impediment by the alkyl groups, is as for nitrosation in aqueous media (methyl- ethyl- propyl- butyl- > allyl-urea). 

The rate-pD profile for the 2-position could be accounted for by parallel rate-determining proton abstraction from the conjugate acid of imidazole by OD and by DgO leading to an ylide intermediate (Scheme 2). These pathways together with OD -catalyzed proton abstraction from the neutral imidazole molecule accounted for the 4(5)-... 

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