Solvent effects solvolysis reactions

The choice of an appropriate solvent as the reaction medium is of primary importance and usually involves a compromise among various unfavorable factors. Because of the high chemical reactivity of the halogens and of the polyhalides, solvents which are easily susceptible to halo-genation or which effect solvolysis reactions are to be avoided. This, of course, precludes the use of aqueous solutions for many syntheses, with the exception of those of some polyiodides since iodine is fairly unreactive with water. 

Winstein suggested that two intermediates preceding the dissociated caibocation were required to reconcile data on kinetics, salt effects, and stereochemistry of solvolysis reactions. The process of ionization initially generates a caibocation and counterion in proximity to each other. This species is called an intimate ion pair (or contact ion pair). This species can proceed to a solvent-separated ion pair, in which one or more solvent molecules have inserted between the caibocation and the leaving group but in which the ions have not diffused apart. The free caibocation is formed by diffusion away from the anion, which is called dissociation. 

Stabilization of a carbocation intermediate by benzylic conjugation, as in the 1-phenylethyl system shown in entry 8, leads to substitution with diminished stereosped-ficity. A thorough analysis of stereochemical, kinetic, and isotope effect data on solvolysis reactions of 1-phenylethyl chloride has been carried out. The system has been analyzed in terms of the fate of the intimate ion-pair and solvent-separated ion-pair intermediates. From this analysis, it has been estimated that for every 100 molecules of 1-phenylethyl chloride that undergo ionization to an intimate ion pair (in trifluoroethanol), 80 return to starting material of retained configuration, 7 return to inverted starting material, and 13 go on to the solvent-separated ion pair. 

A unimolecular ionization was shown to be the mechanism of solvolysis by means of rate studies, solvent effects, salt effects, and structural effects (179,180). The products of reaction consist of benzo [bjthiophen derivatives 209 or nucleophilic substitution products 210, depending upon the solvent system employed. By means of a series of elegant studies, Modena and co-workers have shown that the intermediate ion 208 can have either the open vinyl cation structure 208a or the cyclic thiirenium ion 208b, depending... 

This reaction proceeds via the transition state illustrated in Fig. 10.2. An Sn2 reaction (second order nucleophilic substitution) in the rate limiting step involves the attack of the nucleophilic reagent on the rear of the (usually carbon) atom to which the leaving group is attached. The rate is thus proportional to both the concentration of nucleophile and substrate and is therefore second order. On the other hand, in an SnI reaction the rate limiting step ordinarily involves the first order formation of an active intermediate (a carbonium ion or partial carbonium ion, for example,) followed by a much more rapid conversion to product. A sampling of a and 3 2° deuterium isotope effects on some SnI and Sn2 solvolysis reactions (i.e. a reaction between the substrate and the solvent medium) is shown in Table 10.2. The... 

Extensive studies have been carried out on the concentrated salt effects on the solvolysis reaction rates of aliphatic halides and related compounds in acetone-water mixed solvents. The main outcome of the complicated results presented appears to be that Tt is proposed that one could simply distinguish 5n1 from 5n2 reactions merely by observing a substantial increase in the solvolysis rate constant at 1.0 mol dm LiC104 in aqueous mixed solvents. ... 

There is an ongoing controversy about whether there is any stabilization of the transition state for nucleophilic substitution at tertiary aliphatic carbon from interaction with nucleophilic solvent." ° This controversy has developed with the increasing sophistication of experiments to characterize solvent effects on the rate constants for solvolysis reactions. Grunwald and Winstein determined rate constants for solvolysis of tert-butyl chloride in a wide variety of solvents and used these data to define the solvent ionizing parameter T (Eq. 3). They next found that rate constants for solvolysis of primary and secondary aliphatic carbon show a smaller sensitivity (m) to changes in Y than those for the parent solvolysis reaction of tert-butyl chloride (for which m = 1 by definition). A second term was added ( N) to account for the effect of changes in solvent nucleophilicity on obsd that result from transition state stabilization by a nucleophilic interaction between solvent and substrate. It was first assumed that there is no significant stabilization of the transition state for solvolysis of tert-butyl chloride from such a nucleophilic interaction. However, a close examination of extensive rate data revealed, in some cases, a correlation between rate constants for solvolysis of fert-butyl derivatives and solvent nucleophicity. " ... 

The solvent may serve only as the medium for the reaction, or it may in addition be a reactant, as in a solvolysis reaction. It is possible that the reaction mechanism may be changed by a change in solvent (e.g., from SnI to Sn2) or that the rate-determining step of a complex reaction may be altered. All of these phenomena can be studied by examining the solvent dependence. One goal of research on medium effects is to achieve a level of understanding that will allow us to make mechanistic interpretations from such data. Handbooks of solubility parameters are valuable (Barton, 1983). 

The preceding sections have shown the complexity of solvent effects in the solvolysis of acyl chlorides, and how ambiguities in the role of the solvent, particularly in its apparent reaction order, critically affect the assignment of detailed mechanism. It is the intention in this brief section to point to some of... 

In summary, therefore, the detailed mechanism of the hydrolysis of carboxylic anhydrides is still in doubt and we must hope for further experimental evidence to clarify the position. As for the hydrolysis of the other carboxylic acid derivatives dealt with in this chapter, none of the mechanistic criteria, that have been used to interpret the kinetic data, gives an unambiguous interpretation, resulting in a situation where details of mechanism are open to argument. This is particularly the case for solvolysis reactions where uncertainty as to the structure and effect of the solvent preclude a firm assignment of transition state structures. This is not to say that the mechanisms are not... 

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. 

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... 

It has been recognized that the solvent isotope effect on solvolysis reactions is a disappointing piece of information (Laughton and Robertson, 1969a Schowen, 1972), since, regardless of mechanism, the substitution of DzO for H20 produces very much the same rate ratio. Some typical results are collected together in Table 19. The puzzling feature is that one would expect Sn2 reactions to have more pronounced solvent isotope effects than SN1... 

An analysis of these results in terms of solvent effects leads to the observation of similarities with Ritchie s work on the N+ relation. Thus the constant selectivities obtained in the solvolysis reactions of certain methyl derivatives (Table 9) may indicate the existence of a basic similarity between the rate-determining process in these reaction and in the electrophile-nucleophile combination reactions correlated by the IV+ relation. The failure of the methyl halides to conform to this pattern might suggest that their substitution reactions are fundamentally different, and that the free energy of activation is dependent on factors other than desolvation. 

The difficulties encountered in using the analysis of substituent effects in solvolyses as a mechanistic probe mostly arise from the mechanistic involvement of the solvent (Shorter, 1978, 1982 Tsuno and Fujio, 1996). Consequently, the behaviour of benzylic carbocations in the gas phase should be the best model for the behaviour of the solvolysis intermediate in solution (Tsuno and Fujio, 1996). The intrinsic substituent effects on the benzylic cation stabilities in the gas phase have also been analysed by equation (2), and they will be compared here with the substituent effects on the benzylic solvolysis reaction. In our opinion, this provides convincing evidence for the concept of varying resonance demand in solvolysis. Finally, we shall analyse the mechanisms of a series of benzylic solvolysis reactions by using the concept of a continuous spectrum of varying resonance demand. 

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