Solvolytic reactions, isotope effects

Mechanisms, of proton transfer between oxygen and nitrogen acids and bases in aqueous solutions, 22, 113 Mechanisms, organic reaction, isotopes and, 2, 1 Mechanisms of reaction, in solution, entropies of activation and, 1, 1 Mechanisms of reaction, of /3-lactam antibiotics, 23, 165 Mechanisms of solvolytic reactions, medium effects on the rates and, 14, 10 Mechanistic analysis, perspectives in modern voltammeter basic concepts and, 32, 1 Mechanistic applications of the reactivity-selectivity principle, 14, 69 Mechanistic studies, heat capacities of activation and their use, 5, 121 Mechanistic studies on enzyme-catalyzed phosphoryl transfer, 40, 49 Medium effects on the rates and mechanisms of solvolytic reactions, 14, 1 Meisenheimer complexes, 7, 211... 

As mentioned above in the introductory section, this survey will be selective rather than all-inclusive. To begin with, some early work on isotope effects in solvolytic reactions which was interpreted in steric terms, and which in part actually pre-dates the treatment of BarteU (1960, 1961a, b) will be reviewed. 

Solvolytic experiments specifically designed to test Bartell s theory were carried out by Karabatsos et al. (1967), who were primarily interested in an assessment of the relative contributions of hyperconjugation and non-bonded interactions to secondary kinetic isotope effects. Model calculations of the (steric) isotope effect in the reaction 2- 3 were performed, as well as that in the solvolyses of acetyl chloride... 

For reviews, see L. Melander, Isotope Effects on Reaction Rates, Ronald Press, New York, 1960 F.W. Westheimer, Chem. Rev., 61, 265 (1961) Streitwieser, A., Jr., Solvolytic Displacement Reactions, McGraw-Hill, New York, 1962 E. H. Halevi,Prog Phys. Org. Chem., 1, 109 (1963) C. J. Collins and N. S. Bowman, eis.. Isotope Effects in Chemical Reactions, Van Nostrand Reinhold Co., New York, 1970. 

These structures were then used to generate the force fields and calculate the secondary /3-deuterium-d6 equilibrium isotope effects (EIEs) for the formation of the isopropyl carbocation (Table 30). Because the transition states for formation of the carbocation will be close to the structure of the carbocation, these KIEs should be excellent approximations of the maximum secondary /3-deuterium KIEs expected for the limiting SN1 solvolytic reaction. 

Secondary deuterium isotope effects are important in the study of neighbouring-group participation in solvolytic reactions.61 This subject has now been reviewed at considerable length. Other evidence bearing on participation is also discussed. 

It is generally agreed that the mechanism of the solvolysis of benzyl halides lies near the region which marks the transition from Sjfl to Sjf2 solvolysis. Considerations of the kinetic chlorine isotope effect have recently led to the conclusion that even 4-nitrobenzyl chloride undergoes Sul solvolysis (Hhl and Pry, 1962) but an examination of the data suggests that this effect does not represent a sensitive test of solvolytic mechanism (Kohnstam, 1967). On the other hand, the values oi AC, AC I AS, and AS show that the solvolysis of the parent compoimd has the characteristic featvues of an 8 2 reaction (Tables 5, 6), and other evidence also supports this conclusion (see Bensley and Kohnstam, 1957). 

Primary and secondary kinetic isotope effects are of general importance in the study of neighboring group participation. Isotopic substitution a to the incipient carbo-cation produces a secondary isotope effect whereas 0 and y substituents may give rise to both primary and secondary effects. For example, if the rate determining step of a solvolytic reaction involves a hydrogen shift or elimination, primary deuterium isotope effects are clearly implicated. 

Secondary kinetic isotope effects provide one of the most subtle probes of reaction mechanism currently available as the perturbation of the system under study is small. Unfortunately, the interpretation of isotope effects is far from straightforward. There is no general agreement about the mechanistic significance of a-deuterium isotope effects in solvolytic reactions. The interpretation of more remote deuterium isotope effects appears to be even more complex. 

Methyl-d3 isotope effects and 0L-methyl hydrogen rate effects in solvolytic reactions... 

In the solvolysis of cyclopentyl brosylate the increase in the isotope effect /c(H)/7c(/S d4) with increasing solvent ionizing power has been interpreted as evidence for a rate-limiting elimination in the more polar solvent207. Investigation of a much larger number of substituents is needed to understand the effect of electron-withdrawing a-substituents on solvolytic reactions. 

The above brief outline indicates that secondary deuterium isotope effect studies provide a powerful supplementary isotopic technique, shedding new light on obscure kinetic problems encountered in nucleophilic solvolytic substitution reactions with sulphonate esters215-217. 

Though secondary deuterium isotope effects were first observed in solvolytic reactions, historical priority alone is no compelling argument for priority of discussion. A sounder justification is that the solvolytic effects are easiest of all secondary isotope effects to understand in the light of what we have said earlier. 

Saunders and coworkers have applied the isotopic perturbation technique to a number of persistent carbocations and have demonstrated that C—H hyperconjugation is a principal cause of P-secondary deuterium equilibrium isotope effects in stable carbocations. The results fully support the interpretation of secondary kinetic isotope effects in solvolytic substitution reactions. 

The low values obtained for the secondary deuterium kinetic isotope effects in the comparative solvolyses of (141) and (142) in formic acid (kn/ko = 1.154 at 29.9 °C) and in aqueous ethanol kji/ko = 1.116 at 64.4 °C) are regarded as evidence for extensive bridging (143) in the solvolytic transition state the deuterium atom at the C-1 bridgehead in (142) obviates the scrambling problem.As the contribution from the P-deuterium is unknown, then assuming the effects of a- and -deuterium are cumulative the tt-kinetic isotope effect is further decreased from the value expected for reaction occurring without nucleophilic assistance. The products of solvolysis of ent-methyl-12p-p-tolylsulphonyloxybeyeran-19-oate, which is a related bicyclo [3,2,1 ] -octan-2-yl system, have been discussed in terms of intermediate carbocation stabilities and lifetimes in the solvent employed. ... 

The relation of solvolytic 3-effects to hyperconjugation was pointed out very early by Lewis and Boozer (6). Subsequent research was primarily concerned with establishing whether hyperconjugation alone, or hyperconjugation as the dominant factor, could interpret solvolytic isotope effects adequately. This research took three principal directions (i) The solvent and temperature dependence (ii) The relation of /3-isotope effects to the steric requirements of hyperconjugation (iii) The effects of isotopic substitution at points farther removed from the site of reaction. The first two of these lines of investigation will be discussed under (1) and (3) of this section, and the third will be deferred until Sec. VB, 4(b). 

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