Cation solvent isotope effects

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

The second step in acetal and ketal hydrolysis is conversion of the hemiacetal or hemiketal to the carbonyl compound. The mechanism of this step is similar to that of the first step. Usually, the second step is faster than the initial one. Hammett a p plots and solvent isotope effects both indicate that the transition state has less cationic character than... 

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. 

The experiments of Bott (17) and Noyce (19-21) show that a vinyl cation best represents the intermediate in the hydration of phenylacetylenes. In particular, the large solvent Isotope effects observed indicate a rate-limiting protonation and formation of a vinyl cation, for these values are not in agreement with solvent isotope effects observed for compounds which react by other possible mechanisms, such as one involving equilibrium formation of the vinyl cation followed by the slow attack by water. 

Increasing numbers of nitrogen atoms increase not only the kinetic susceptibility toward attack but also the thermodynamic stability of the adducts. Reversible covalent hydration of C = N bonds has been observed in a number of heterocyclic compounds (76AHC(20)117). Pyrimidines with electron-withdrawing groups and most quinazolines show this phenomenon of covalent hydration . Thus, in aqueous solution the cation of 5-nitropyrimidine exists as (164) and quinazoline cation largely as (165). These cations possess amidinium cation resonance. The neutral pteridine molecule is covalently hydrated in aqueous solution. Solvent isotope effects on the equilibria of mono- (166) and dihydration (167) of neutral pteridine as followed by NMR are near unity (83JOC2280). The cation of 1,4,5,8-tetraazanaphthalene exists as a bis-covalent hydrate (168). 

Detailed studies of the temperature dependence of the kinetics of cation-pseudobase equilibration have been reported92 for three cations, and activation parameters have been evaluated for each of k0H, kH20, kt, and k2 in these cases. Whereas entropies of pseudobase formation from the cation are positive (Section III), the entropies of activation associated with k0H are quite negative (-11 to -17 cal mol-1 deg-1). For direct hydroxide ion attack on the cation via transition state A, one would predict an entropy of activation similar to the entropy of formation of the pseudobase from heterocyclic cation and hydroxide ion. Interpretation of k0H in terms of transition state B in which hydroxide ion acts as a general-base catalyst for the attack of a water molecule seems to be more consistent with the observed entropies of activation. The k2 step, which is the microscopic reverse of fcoH would then be interpreted as general-acid-catalyzed (by a water molecule) decomposition of the neutral pseudobase to the cation. These interpretations of /cqH and k2 are also consistent with the observed solvent isotope effects for the reactions in HzO and DzO and with the presence of general... 

Hydrolysis of acetals by acid is considered to proceed normally via the A1 mechanism. Electron release in the aldehyde facilitates reaction, the p value being —3.5, indicating stabilization of a cationic intermediate. The solvent isotope-effect k H2O/ D2O is approximately 2.6, which indicates that the acidic property of the solvent is more important than its nucleophilicity. The entropy of activation is positive, 5-20 K l mol-1. Glycopyranosides fit into this generalization, but the acidic hydrolysis of the corresponding furanosides shows negative entropies of activation, indicating a difference in mechanism. 

Alkynes are somewhat less reactive than alkenes. For example, 1-butene is 20 times more reactive than 1-butyne in 8.24 M112804. " Alkyne reactivity increases with the addition of ERG substituents. Solvent isotope effects are indicative of a ratedetermining protonation. " These reactions are believed to proceed by rate-determining proton transfer to give a vinyl cation. Reactions proceeding through a vinyl cation would not be expected to be stereospecific, since the cation will adopt sp hybridization (see Section 3.4.1). 

Under these conditions, the primary reactions after the formation of the diazoalkane cation radical can be studied. First-order kinetics were found. The rates are independent of pyridine and methanol and there is practically no deuterium isotope effect in tetradeuterated methanol. The solvent isotope effect (CD3CN and CD3OD and its mixtures) is minimal (e.g., kcH oa/f CD OD = 1-02). These results indicate a simple unimolecular dissociation of the CN bond, forming the dinitrogen molecule and the carbene cation radical. 

Evidence that a 1,2-dihydroxycyclohexadienide anion is stabilized by aromatic negative hyperconjugation has been described. It complements an earlier inference of positive hyperconjugative aromaticity for the cyclohexadienyl cation. The anion is a reactive intermediate in the dehydration of benzene cw-l,2-dihydrodiol to phenol. The measurements of the solvent isotope effects are consistent with reaction via a carbanion intermediate or a concerted reaction with a carbanionlike transition state. These confirm that the reaction proceeds by a stepwise mechanism, with a change in ratedetermining step from proton transfer to the loss of hydroxide ion from the intermediate. 

However, a number of examples have been found where addition of bromine is not stereospecifically anti. For example, the addition of Bf2 to cis- and trans-l-phenylpropenes in CCI4 was nonstereospecific." Furthermore, the stereospecificity of bromine addition to stilbene depends on the dielectric constant of the solvent. In solvents of low dielectric constant, the addition was 90-100% anti, but with an increase in dielectric constant, the reaction became less stereospecific, until, at a dielectric constant of 35, the addition was completely nonstereospecific.Likewise in the case of triple bonds, stereoselective anti addition was found in bromination of 3-hexyne, but both cis and trans products were obtained in bromination of phenylacetylene. These results indicate that a bromonium ion is not formed where the open cation can be stabilized in other ways (e.g., addition of Br+ to 1 -phenylpropene gives the ion PhC HCHBrCH3, which is a relatively stable benzylic cation) and that there is probably a spectrum of mechanisms between complete bromonium ion (2, no rotation) formation and completely open-cation (1, free rotation) formation, with partially bridged bromonium ions (3, restricted rotation) in between. We have previously seen cases (e.g., p. 415) where cations require more stabilization from outside sources as they become intrinsically less stable themselves. Further evidence for the open cation mechanism where aryl stabilization is present was reported in an isotope effect study of addition of Br2 to ArCH=CHCHAr (Ar = p-nitrophenyl, Ar = p-tolyl). The C isotope effect for one of the double bond carbons (the one closer to the NO2 group) was considerably larger than for the other one. ... 

---