Borderline-SN2 mechanism

Because such reactions have features of both the SN2 mechanism (stereochemistry) and the SN1 mechanism (regiochemistry), they are said to follow a borderline SN2 mechanism. The transition state geometry resembles that for an SN2 reaction, but the bond to the leaving group is broken to a greater extent than the bond to the nucleophile is formed, resulting in considerable positive charge buildup on the carbon. Therefore, the transition state that has... 

If the electrophile has an unshared pair of electrons, the reaction is one from Table 11.3 and proceeds through a three-membered cyclic intermediate, which is formed by syn addition. If the cyclic intermediate is neutral, the reaction stops here. If the intermediate is chained, the nucleophile adds with inversion (borderline SN2 mechanism), resulting in overall anti addition. 

With further shift into the direction of still more advanced breaking of the bond within active species this borderline Sn2 mechanism could eventually convert into the Sjql mechanism. This should be promoted by the presence of the stabilizing group located closely to the carbe-nium ion (like in cyclic acetals polymerization) and/or high ring strain (like in the three membered rings). Indeed, contribution of Sj l mechanism in both cases has been postulated for polymerization of 1,3-dioxolane and isobutylene oxide but there is still no clear-cut evidence for its operation. 

Some reactions of a given substrate under a given set of conditions display all the characteristics of Sn2 mechanisms other reactions seem to proceed by SnI mechanisms, but cases are found that cannot be characterized so easily. There seems to be something in between, a mechanistic borderline region. At least two broad theories have been devised to explain these phenomena. One theory holds that intermediate behavior is caused by a mechanism that is neither pure Sn I nor pure Sn2, but some in-between type. According to the second theory, there is no intermediate mechanism at all, and borderline behavior is caused by simultaneous operation, in the same flask, of both the SnI and Sn2 mechanisms that is, some molecules react by the SnI, while others react by the Sn2 mechanism. 

The difference between the SnI and Sn2 mechanisms is that in the former case the formation of the ion pair (ki) is rate determining, while in the Sn2 mechanism its destruction ( 2) i rate determining. Borderline behavior is found where the rates of formation and destruction of the ion pair are of the same order of magnitude. However, a number of investigators have asserted that these results could also be explained in other ways. ... 

Among the experiments that have been cited for the viewpoint that borderline behavior results from simultaneous SnI and Sn2 mechanisms is the behavior of 4-methoxybenzyl chloride in 70% aqueous acetone. In this solvent, hydrolysis (i.e., conversion to 4-methoxybenzyl alcohol) occurs by an SnI mechanism. When azide ions are added, the alcohol is still a product, but now 4-methoxybenzyl azide is another product. Addition of azide ions increases the rate of ionization (by the salt effect) but decreases the rate of hydrolysis. If more carbocations are produced but fewer go to the alcohol, then some azide must he formed by reaction with carbocations—an SnI process. However, the rate of ionization is always less than the total rate of reaction, so some azide must also form by an Sn2 mechanism. Thus, the conclusion is that SnI and Sn2 mechanisms operate simultaneously. ... 

The perchloric acid-catalyzed methanolysis of 2-methyloxetane gives a mixture of 4-methoxy-2-butanol and 3-methoxy-l-butanol, with the former somewhat predominating (equation 21). The effect of solvent on the product distribution and the reaction rates indicated that protonated 2-methyloxetane was reacting by a borderline n1-Sn2 mechanism (67MI51302). Similar studies with the acid-catalyzed methanolysis of oxetane itself indicated that methanol reacted with protonated oxetanium ion by the N2 process. The same type of studies with a series of 2-aryloxetanes indicated that methanolysis of these compounds involved the borderline mechanism for the protonated oxetanium ions (69MI5101, 72MI5102, 73MI5100). 

Further support for this interpretation can be found by considering the data for the hydrolysis of isopropyl compounds in Table 28. The values of r are calculated from (112). It can be seen that the transition states for the isopropyl transfers are much looser than those for the methyl transfers. The solvolysis of isopropyl compounds is closer to the borderline between the SN1 and SN2 mechanisms and therefore we may expect the SN2 transition state to be looser. As discussed above there is supporting evidence from Ko and Parker s (1968) measurements of transfer activity coefficients for the transition state. 

Some reactions of a given substrate under a given set of conditions display all the characteristics of Sn2 mechanisms other reactions seem to proceed by SnI mechanisms, but cases are found that cannot be characterized so easily. There seems to be something in between, a mechanistic borderline region. At least two broad... 

Borderline-SN2-Type Mechanism. Some enzymes, such as limonene-1,2-epoxide hydrolase, have been shown to operate via a single-step push-pull mechanism [573]. General acid catalysis by a protonated aspartic acid weakens the oxirane to facilitate a simultaneous nucleophilic attack of hydroxyl ion, which is provided by deprotonation of H2O via an aspartate anion. Due to the borderline-SN2-character of this mechanism, the nucleophile preferentially attacks the higher substituted carbon atom bearing the more stabilized 5 -charge. After liberation of the glycol, proton-transfer between both Asp-residues closes the cycle. 

Scheme 2.87 Sn2- and borderline-SN2-type mechanism of epoxide hydrolases...

Secondary alkyl halides occupy a borderline region in which the nature of the nucleophile is the main determining factor in respect to the mechanism. Secondary alkyl hahdes usuaUy react with good nucleophiles by the Sn2 mechanism, and with weak nucleophiles by SnI. 

Several proposals have been made to fit the borderline reactions into a well-defined mechanistic scheme. Most of these adopt one of two viewpoints either (1) borderline substrates undergo concurrent SnI and Sn2 processes, with the particular system determining which mechanism, if either, predominates or (2) all Sn reactions are related by essentially the same mechanism, which differs from case to case in the detailed disposition of electrons in the transition state. In this view pure SnI and Sn2 processes are merely the extreme limiting forms of a single mechanism, and the borderline mechanism is a merged process having some features of both. 

The notion of concurrent SnI and Sn2 reactions has been invoked to account for kinetic observations in the presence of an added nucleophile and for heat capacities of activation,but the hypothesis is not strongly supported. Interpretations of borderline reactions in terms of one mechanism rather than two have been more widely accepted. Winstein et al. have proposed a classification of mechanisms according to the covalent participation by the solvent in the transition state of the rate-determining step. If such covalent interaction occurs, the reaction is assigned to the nucleophilic (N) class if covalent interaction is absent, the reaction is in the limiting (Lim) class. At their extremes these categories become equivalent to Sn and Sn , respectively, but the dividing line between Sn and Sn does not coincide with that between N and Lim. For example, a mass-law effect, which is evidence of an intermediate and therefore of the SnI mechanism, can be observed for some isopropyl compounds, but these appear to be in the N class in aqueous media. 

Sneen et al. formulated an intermediate-mechanism theory. The formulation is in fact very broad and applies not only to borderline behavior but to all nucleophilic substitutions at a saturated carbon. According to Sneen, all SnI and Sn2 reactions can be accommodated by one basic mechanism (the ion-pair mechanism). The substrate first ionizes to an intermediate ion pair that is then converted to products ... 

The yield of the nucleophilic substitution product from the stepwise preassociation mechanism k[ = k. Scheme 2.4) is small, because of the low concentration of the preassociation complex (Xas 0.7 M for the reaction of X-2-Y). Formally, the stepwise preassociation reaction is kinetically bimolecular, because both the nucleophile and the substrate are present in the rate-determining step ( j). In fact, these reactions are borderline between S l and Sn2 because the kinetic order with respect to the nucleophile cannot be rigorously determined. A small rate increase may be due to either formation of nucleophile adduct by bimolecular nucleophilic substitution or a positive specific salt effect, whUe a formally bhnole-cular reaction may appear unimolecular due to an offsetting negative specific salt effect on the reaction rate. 

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