Nucleophile solvent participation

The importance of solvent participation in the borderline mechanisms should be noted. Nucleophilic participation is minimized by high electronegativity, which reduces the Lewis basicity and polarizability of the solvent molecules. Trifluoroacetic acid and perfiuoro alcohols are among the least nucleophilic of the solvents used in solvolysis studies. These solvents are used to define the characteristics of reactions proceeding without nucleophilic solvent participation. Solvent nucleophilicity increases with the electron-donating capacity of the molecule. The order trifluoroacetic acid < trifluoroetha-nol <acetic acid < water < ethanol gives a qualitative indication of the trend in solvent nucleophilicity. More will be said about solvent nucleophilicity in Section 5.5. 

Reactant structure will also influence the degree of nucleophilic solvent participation. Solvation is minimized by steric hindrance. The 2-adamantyl system is regarded as being a... 

Similar changes in nucleophilic (or dipole) solvation (Scheme 2.8A) provide a simple explanation for the observation of other correlations between rate constants for solvolysis and solvent nucleophilicity. This interpretation does not require that there be stabilization of the transition state for solvolysis of tertiary derivatives by a partial covalent interaction between nucleophile and electrophile. We have defined this latter interaction as nucleophilic solvent participation (Scheme 2.8B) and have argued that the results of simple and direct experiments to detect stabilization of the transition state for reaction of simple tertiary derivatives by... 

In summary, controversy concerning the mechanism for solvolysis at tertiary carbon is semantic and can be avoided by making a clear distinction between (a) nucleophilic solvation, which is stabilization of the transition state for stepwise solvolysis through carbocation or ion pair intermediates by charge-dipole interactions with nucleophilic solvents (Scheme 2.8A) and, (b) nucleophilic solvent participation, which is stabihzation of the transition state for concerted solvolysis by formation of a partial covalent bond to the solvent nucleophile (Scheme 2.8B). 

J. P. Richard, M. M. Toteva, and T. L. Amyes, What is the Stabihzing Interaction with Nucleophibc Solvents in the Transition State for Solvolysis of Tertiary Derivatives Nucleophilic Solvent Participation or Nucleophilic Solvation Org. Lett. 2001, 3, 2225. 

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 limiting nature of the solvolysis reactions of 2-adamantyl solvolyses apparently arises as a result of steric inhibition of rearside nucleophilic solvent participation by the axial hydrogens shown in 95. Such steric effects are absent... 

Traditionally, relative stabilities of carbocations have been derived from the comparison of the rates of solvolysis reactions following the SN1 mechanism, for which the designation Dm + An has recently been proposed [36], The comparison of solvolytic rate constants for substrates of a large structural variety is hampered by the fact that the published solvolysis rates refer to different solvents, different temperatures, and precursors with different leaving groups. Dau-Schmidt has, therefore, converted solvolysis rates of a manifold of alkyl chlorides and bromides to standard conditions, i.e., soiv of RC1 in 100% EtOH at 25° C (Scheme 6) [37]. Although from a theoretical point of view, ethanol is not an ideal solvent for observing unassisted SN 1-type reactions (nucleophilic solvent participation), it has been selected as the reference solvent because most available experimental data have been collected in solvents of comparable nucleophilicity, a fact which made conversions to 100% ethanol relatively unproblematic [38],... 

Adamantyl and Homoadamantyl Cations. The 2-adamantyl system is exceptional among sec-alkyl substrates since it solvolyzes without nucleophilic solvent participation (Section 7.2.1). The extent of anchimeric assistance is more difficult to evaluate. Some evidence is consistent with a weakly bridged intermediate ... 

I. Further work from Liu s group has involved B-strain and solvolytic reactivity revisited. Nucleophilic solvent participation and abnormal rate ratios for tertiary chloroalkanes. The abnormal rate ratios are those involving introducing FV, and are considered due to competition between B strain and nucleophilic solvent participation. In presenting solvolytic studies of 4-methoxybenzyl chloride and bromide, and of l-(4-methoxyphenyl)ethyl chloride, further opportunity was taken to criticize the introduction and use of the aromatic ring parameter /. ... 

Kinetic and Stereochemical Tests for Nucleophilic Solvent Participation... 

As a test of the extent of nucleophilic solvent participation in transition states in the borderline or combat zone region, we studied 1-arylethyl... 

Solvolyses of systems ArAr C(OTs)CF3 and the related bromides have also been studied and also show rate decelerations of approximately 105 for CF3 relative to hydrogen (35, 36). The highly crowded nature of these substrates appears to preclude any kinetically important nucleophilic solvent participation. The constancy of the k(R)/k(CF3) rate ratios in comparison to less crowded systems suggests either that no steric effects involve the CF3 groups on the kc reactivity of these substrates or that any such effects tend to cancel. 

Before leaving the discussion of possible mechanisms, it should be pointed out that they ntav not be as distinctly separated in concept as it may have appeared in their individual descriptions. The distinction between SNI and SN-2 in solvolysis reactions is blurred by the probability of varying degrees of nucleophilic solvent participation in the S, I transition slate [72]. Within SN2 (eq. 2.8) there can be different extents of bond breaking and bond making in the transition state at one extreme, a loose transition state with a nearly broken bond to I. but little bond making to Nu could be described as SNl-like (72. Second-order kinetics may also be expected if Nu reacts with an ion pair formed by rapid, reversible ionization of RL [73. ... 

The role of nucleophilic solvent participation is more clearly developed in the case of bromine addition to alkynes Modena, G. Rivetti, F. Tonellato, U. /. Org. Chem. 1978, 43,1521. 

The reason that the adamantyl system is much more sensitive to the substitution of CH3 for H is that it has no nucleophilic solvent participation while the 2-propyl system has much stronger solvent participation. As was discussed earlier, the adamantyl structure effectively shields the back side of the reacting carbon. 

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