Solvolysis nucleophilic solvent assistance

The effect of a-silyl substitution on the stability of a carbenium ion was qualitatively unclear for a long time. Early solvolytic studies by the groups of liaborn36 and Cartledge37 suggest a destabilizing effect of a-silyl substitution compared with alkyl. The measurement and interpretation of the kinetic a-silicon effect in solvolysis reactions is, however, often complicated by the fact that steric and ground state effects may play an important role and that, in addition, the rates of ionization often involve a contribution from nucleophilic solvent assistance. 

In contrast to typical mono- or acyclic substrates (e. g.,isopropyl), 2-adaman-tyl derivatives are also found to be insensitive to changes in solvent nucleophilicity. A variety of criteria, summarized in Table 13, establish this point. In all cases, the behavior of 2-adamantyl tosylate is comparable to that observed for its tertiary isomer but quite unlike that observed for the isopropyl derivative. Significant nucleophilic solvent participation is indicated in the solvolysis reactions of the isopropyl system. The 2-adamantyl system, on the other hand, appears to be a unique case of limiting solvolysis in a secondary substrate 296). The 2-adamantyl/ isopropyl ratios in various solvents therefore provide a measure of the minimum rate enhancement due to nucleophilic solvent assistance in the isopropyl system 297). 

The solvent acts as a kinetically significant nucleophile in the overall solvolysis process for many simple secondary substrates, and this appears to be the major cause of the variation in relative rates with changes in solvent (Table 2, p. 11). This conclusion is supported by the quantitative correlations discussed in Section 6. The stereochemical evidence further suggests that, even when the magnitude of nucleophilic solvent assistance is less than a rate factor of 10 at 25°, solvolyses (e.g. of cylcohexyl tosylate in formic acid) can proceed with essentially complete inversion of configuration. These results are consistent with an SN 2 mechanism and the evidence for ion pair intermediates can then be considered in one of two ways. 

It may be argued that the evidence for ion pair intermediates is too indirect, since it has not been established that the ion pairs undergoing 18 O-scrambling or interned return are the same as those undergoing solvolysis. Evidence for ion pairs would then be explained by side-reactions and the solvolytic reactions for which nucleophilic solvent assistance is greater... 

Alternatively, if it is accepted that ion pairs are involved in the solvolysis process and that nucleophilic solvent assistance is also significant, then the reaction might proceed via a nucleo-philically-solvated ion-pair intermediate (e.g. [34], Fig. 8). 

Perhaps the most spectacular success of explanations based on solvation of ground states, published to date, is the dissection of activation parameters for solvolysis of t-butyl chloride in mixtures of ethanol and water, first discussed by Winstein and Fainberg (1957). The complex variation of AH and AS (Fig. 21) has been shown to be due almost entirely to ground state solvation effects, at least for the solvents ethanol—40% ethanol/water studied by Arnett et al. (1965). For 90%, 80%, 70%, 60%, 50% and 40% ethanol/water the parameter AH1 for solvation of the transition state (by transfer from the gas phase) was calculated to be linearly proportional to the corresponding value of AS, as expected from the behaviour of simple salts. The point for pure ethanol did not fall on the calculated line, and this was attributed to nucleophilic solvent assistance. The variation in AG, AH and AS (Fig. 21) can be reproduced remarkably well using ethane and the zwitterionic a-amino acid, glycine, as model compounds (Abraham et al., 1975 see also Abraham, 1974 Abraham and Abraham, 1974). 

Raber et al. (1971b) noted that, in addition to 2-octyl mesylate, a number of primary and secondary substrates which also underwent solvolysis with substantial nucleophilic solvent assistance all showed considerably higher selectivities than expected from the reactivity-selectivity relationship illustrated in Fig. 8. They concluded that, while the failure of these points to correlate with the carbocations did point to a mechanistic difference between the two groups, the conclusion... 

Kevill and co-workers first address the much-debated issue of nucleophilic involvement in solvolysis of tert-butyl derivatives. Interestingly, the tert-butyl sulfonium salt shows more rate variation with solvent changes than does the 1-adamantyl salt. In particular, the tert-butyl salt shows a rate increase in aqueous TFEs (where both Y and N increase) that is not found for 1-adamantyl. Because a variation in Y cannot explain the result, Kevill argues that the tert-butyl derivative is receiving nucleophilic solvent assistance. On the basis of the available evidence, Harris et al. (Chapter 17) propose that tert-butyl chloride is inaccurately indicated by some probes to receive nucleophilic solvent assistance because the model system (1-adamantyl chloride) has a different susceptibility to solvent electrophilicity. Kevill and coworkers disagree with this proposal, noting that essentially the same tert-butyl to 1-adamantyl rate ratio is found for the chlorides and the sulfonium salts if solvent electrophilicity were important in one case but not the other, then the rate ratio should vary. 

The initial objective of our work was to quantify solvent effects (particularly solvent nucleophilicity) by adapting the Grunwald-Winstein equation (2) (5). In equation 2, k is the rate of solvolysis of a substrate (RX) in any solvent relative to 80% v/v ethanol-water (k0) and Y is the solvent ionizing power defined by m = 1.000 for solvolyses of tert-butyl chloride at 25 °C. In this chapter, a discussion of equation 2 and similar free-energy relationships is presented. At the time our work began (1969), in collaboration with Schleyer, mechanisms of solvolytic reactions were close to a high in controversy (6-8). More recent mechanistic developments (9-13) are not reviewed in detail here, but increased recognition of the importance of nucleophilic solvent assistance should be noted. 

However, the relatively weak nucleophilic solvent assistance in the solvolysis of 2-endo-norbornyl sulphonate is corroborated, firstly, by the formation of about 8 % of optically active 2-exo-acetate 66 secondly, by a significant decrease in the solvolysis rate of 2-endo-tosylate on introducing 3-exo-substituents shielding the backside approach of solvent molecules... 

Solvolysis rates of tertiary systems where a methyl group is present, have been used to estimate the rate of solvolysis of the corresponding secondary compounds good agreement was obtained between predicted and observed solvolysis rates for several systems which involved nucleophilic solvent assistance. Solvolysis in 60% aqueous acetone of the 3,5-dinitrobenzoate esters of cycloalk-2-en-l-ols labelled with deuterium at the 1-position, showed that little scrambling of the label or racemization occurred in the cyclo-octenol case, ca. 33 % scrambling occurred in the cycloheptenol case, and 56% scrambling occurred in the cyclohexenol case. Therefore, allylic participation, especially in the cyclo-octenol case, was rather weak. ... 

The solvolysis rates of the C-5-substituted epimeric 2-norbomyl p-bromobenzene-sulphonates (92) and (93) and their 2-methyl homologues have been investigated in 60% aqueous ethanol and in 97% hexafluoropropan-2-ol at various temperatures. The rate ratio exo-(92) endo-(92) is solvent-dependent, rising to the value 1746in hexafluoro-propan-2-ol at 25 °C, indicating the absence of internal return for exo-(92) and nucleophilic solvent assistance for endo- 92). The rates for the epimeric brosylates (93) are lower, the exo-brosylate being affected more, even in hexafluoropropan-2-ol. The rate ratio reductions are much less pronounced in the tertiary series. The results are as expected for the stabilization of the transition state from exo-(92) by 0-delocalization or some other electronic effect. 

Medium ring compounds commonly show enhanced solvolysis rates and solvolysis products derived from transannular hydride transfer. Ionisation in these systems may take place with some degree of transannular C—H bond participation, the extent of bridging in the transition state and competitive nucleophilic solvent assistance (A s-process) being broadly and independently variable. 

In the reactions of secondary halides and esters that contain neighboring groups an important, frequently the most important, competing pathway is solvolysis with nucleophilic solvent assistance, the k process. This means that compounds that react without anchimeric assistance or with only weak anchimeric assistance in strongly nucleophilic solvents may react with strong anchimeric assistance in poorly nucleophilic solvents. Obviously the quantity kjk — = kjkc)/(kjkc) (see p. 14) depends on k, as well as on k. ... 

Another widely used comparison, especially in bicyclic systems, is the exojendo rate ratio. This comparison is also fraught with pitfalls. Problems arise because the endo and exo isomers of a polycyclic system have unique configurations and hence different steric requirements. This can affect anchimeric assistance by neighboring groups. In addition there are inherent differences in field effects and nucleophilic solvent assistance. The 350-fold difference in rate constant for acetolysis of exo- and endo-2-norbornyl p-bromobenzenesulfonates [(11) and (12), respectively] was taken as evidence for a participation in the solvolysis of (11) by Winstein... 

Certain irregularities in effects of systematic variations in structure on the solvolytic reactivity of tertiary chloroalkanes have been attributed to the swamping of the relief of B-strain by nucleophilic solvent assistance. A well-known example of such an irregularity is found in the series RCMe2Cl, in which the rate coefficients for solvolysis in 80% aqueous ethanol lie in the order R = Me < Et > i-Pr < r-Bu. In... 

Use of other methods has contributed further to the emerging picture of solvolysis of most secondary systems as being solvent-assisted. For example, the solvolysis rate acceleration on substituting a-hydrogen by CH3 in 2-adamantyl bromide is 107 5, much larger than that found for other secondary—tertiary pairs such as isopropyl-/-butyl. In molecules less hindered than 2-adamantyl, the secondary substrate is accelerated by nucleophilic attack of solvent.100 Rate accelerations and product distributions found on adding azide ion to solvolysis mixtures (Problem 4) also provide confirmatory evidence for these conclu-... 

Returning, then, to the two alternatives for solvolysis mechanisms with which we began this section, it appears that it is indeed possible to construct systems that solvolyze without nucleophilic assistance from solvent. For solvent-assisted reactions, the two alternatives are essentially equivalent we can therefore choose the first alternative as being more consistent with current information. 

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