Solvolysis isotope effects

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. 

In TFE the secondary isotope effect for solvolysis ( h/ d3)s is found to have the value 1.46 and that for Na,Np-rearrangement (kH/kD3)r has the value 1.42 (Szele and Zollinger, 1981). The two isotope effects are similar to the largest values observed in nucleophilic aliphatic substitutions following the DN + AN mechanism (Shiner,... 

Leffek, Llewellyn and Robertson (1960a, b) made careful conductometric determinations of deuterium kinetic isotope effects on the solvolysis rates (in water) of some ethyl, isopropyl and n-propyl sulphonates and halides. In the case of the n-propyl compoimds,... 

It was of course not possible to introduce the deuterium atoms closer than three bonds away from the center of reaction , but the attenuation of the inductive effect with distance was not expected to affect the validity of the conclusions, especially considering the work of Streit-wieser and Klein (1964), who found that the isotope effect per deuterium in the solvolysis of benzhydryl chloride only decreased from 1 9% for deuterium in the ortho positions to l-5% for deuterium in the meta positions. 

What concerns us here are three topics addressing the fates of bromonium ions in solution and details of the mechanism for the addition reaction. In what follows, we will discuss the x-ray structure of the world s only known stable bromonium ion, that of adamantylideneadamantane, (Ad-Ad, 1) and show that it is capable of an extremely rapid degenerate transfer of Br+ in solution to an acceptor olefin. Second, we will discuss the use of secondary a-deuterium kinetic isotope effects (DKie) in mechanistic studies of the addition of Br2 to various deuterated cyclohexenes 2,2. Finally, we will explore the possibility of whether a bromonium ion, generated in solution from the solvolysis of traAU -2-bromo-l-[(trifluoromethanesulfonyl)oxy]cyclohexane 4, can be captured by Br on the Br+ of the bromonium ion, thereby generating olefin and Br2. This process would be... 

Deuterium isotope effects have been found even where it is certain that the C—H bond does not break at all in the reaction. Such effects are called secondary isotope effectsf" the term primary isotope effect being reserved for the type discussed previously. Secondary isotope effects can be divided into a and P effects. In a P secondary isotope effect, substitution of deuterium for hydrogen p to the position of bond breaking slows the reaction. An example is solvolysis of isopropyl bromide ... 

A number of kinetic /J-deuterium isotope effects in the solvolytic generation of vinyl cations have been measured. Stang and co-workers (193) observed a kn /kp = 1.43 in the solvolysis of 237 in 80% aqueous ethanol at 25° C. This effect is considerably larger than the corresponding j8-deuterium... 

The discrepancy in isotope effects observed by Jones and Maness (140) and Stang et al. (193) for the solvolysis of... 

Stang and Hargrove (197) have examined the effect of substituents on the kinetic deuterium isotope effects in the solvolysis of 240 in 80% aqueous ethanol at 50°. The results are shown in Table XVI. The results indicate... 

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... 

It is remarkable that the isotope effects measured for these reactions in the vapor phase are about the same as the solvolysis KIEs measured in aqueous solution. 

In addition to these probes, theoretical calculations are being made in efforts to decide upon the inherently most stable stmcture of the ion. These will be discussed along with the conclusions which have been derived from the study of isotope effects in solvolysis and substituent effects in stabilizing media. 

An excellent review of the use of secondary a and isotope effects in the norbomyl system has recently been written by Scheppele (1972). We shall briefly summarize a few of the factors and conclusions arrived at because of their relevance to the interpretation of other solvolysis data, but the interested reader should turn to that article and the original sources quoted for a more extensive discussion. 

The kinetic isotope effect has its origin in force constant changes occurring at an isotopically substituted position as the react2mt is converted into an activated complex. Hence it provides information about the transition state in the solvolysis reaction, but not necessarily about the stmcture of possible intermediates. This limits the utility of information drawn from isotope studies in resolving the structure of ions under stabilizing conditions. 

Let us now consider Scheppele s discussion of the solvolysis of 2-d-exo- and -endo-bicyclo[2.2.1]hept-2-yl p-nitrobenzoates and p-toluenesulfonates. A maximum a isotope effect of 1 22 is suggested for the limiting solvolysis of simple secondary... 

Isotope effect measurements have been conducted with labelling at the 6- and 3-positions as well as C-2. These results appear to be no more conclusive than those briefly discussed Scheppele s conclusion concerning y effects at Cg in solvolysis of exo-2-norbomyl brosylate being that they are (a) probably inconsistent with classical theory, but (b) not clearly consistent with non-classical theory. Although not resolving the non-classical issue, the studies indicate many difficulties which obscure the interpretation of any rate data. 

KINETIC ISOTOPE EFFECTS Sn DISPLACEMENT REACTIONS SOLVOLYSIS S/N ratio,... 

A solvent kinetic isotope effect (SKIE) of 0.44 from solvolysis in CD3CN-H2O versus CD3CN-D2O mixtures was in line with predicted values for the protonation-dissociation mechanism for which the SKIE should be between 0.48 and 0.33 (Figure 18a... 

In contrast, the acid-catalyzed hydrolysis of alkyl selenates is A-2158. The actual species which undergoes decomposition to alcohol and sulfur trioxide is probably the zwitterion as in the case of phosphate monoester monoanions. Evidence for sulfur trioxide as the reactive initial product of the A-1 solvolysis is obtained from the product compositions arising with mixed alcohol-water solvents. The product distribution is identical to that found for sulfur trioxide solvolysis, with the latter exhibiting a three-fold selectivity for methanol. Although the above entropies of activation and solvent deuterium isotope effects do not distinguish between the conventional A-l mechanism and one involving rate-limiting proton transfer, a simple calculation, based on the pKa of the sulfate moiety and the fact that its deprotonation is diffusion controlled. 

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