Isotope effects steric

There is an alternative mechanism by which we can see isotope effects in cases that do not involve breaking or making C-H bonds. This is a steric effect, in which the differing effective steric sizes of H vs. D come into play. In a C-H vs. a C-D bond, not only is the ZPE less for D, but we should also anticipate that the vibrational amplitude should be less for D than for H. This in turn should make D appear to be smaller than H in some contexts. 

A classic demonstration of this effect is in the racemization of the chiral biphenyl compound characterized by Mislow and shown in Eq. 8.6. Rotation about the central bond race-mizes the material and forces a severe steric clash between the two methyl groups in the transition state. Indeed, it is found that the deuterio compound racemizes faster than the protio, consistent with the notion that D is effectively smaller than H. The effect is certainly not a large one, as only a 15% difference is seen in a system with a really severe steric interaction and with multiple H/D substitutions. Nevertheless, steric isotope effects can be comparable to other secondary isotope effects, and so should be considered when evaluating experimental data. 

and Fitzpatrick, P. F. pH and Secondary Kinetic Isotope Effects on the Reaction of d-Amino Acid Oxidase withNitroalkane Anions Evidence for Direct Attack on the Flavin by Carbanicms. . Am. Chem. Soc., 119,1155(1997). 

An Ingenious Method for Measuring Very Small Isotope Effects 

Heavy atom and secondary hydrogen kinetic isotope effects are often quite small, so they can be difficult to measure due to the error values often associated with rate constants. However, as any reaction occurs, the reactants are incrementally enriched in the slower reacting components. Thus, for reactants with the natural abundance of heavy isotopes, near the end of the reaction the proportion of heavy isotopes in the reactants has increased relative to the proportion present at the beginning of the reaction. 

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Steric isotope effects may be ascribed to differences in effective size of isotopic atoms. The early part of our discussion will be concerned with the problem of the meaning of this concept. The experimental results which are to be explained are differences in the positions of chemical equilibria and in reaction velocities arising from this difference in size . 

Studies of the molar volumes of perdeuteriated organic compounds might be expected to be informative about non-bonded intermolecular forces and their manifestations, and such studies might be considered to obviate the necessity of investigating steric isotope effects in reacting systems. The results from non-reacting systems could then be simply applied to the initial and transition states in order to account for a kinetic steric isotope effect. 

In the following, a detailed exposition of Bartell s (1961a) theory of steric isotope effects will be given (Section II, A), and an alternative model will be developed, based on somewhat different assumptions about the timing in the transition state, which leads to predictions at variance with the experimental results (Section II, B). In both of these sub-sections, special reference will be made to the work of Melander and Carter (1964). Finally, a selective non-comprehensive review of other experimental work in this field will be presented (Section III). 

As already indicated above, kinetic studies of steric isotope effects afford a possibility of testing our present ideas about the transition state. Bartell s perturbation treatment (Section II, A) involves a timeaveraging of the repulsion energy with respect to the ordinary vibrational motion within the transition state. The passage through the... 

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... 

The molecules most profitably studied in connection with purely steric isotope effects have been isotopically substituted biphenyl derivatives. Mislow et al. (1964) reported the first more or less clearcut example of this kind in the isotope effect in the configurational inversion of optically active 9,10-dihydro-4,5-dimethylphenanthrene (7), for which an isotopic rate ratio ( d/ h) of 1-17 at 295-2°K in benzene solution was determined. The detailed conformation of the transition state is not certain in this case, as it involves the mutual passage of two methyl groups, and thus it is difficult to compare the experimental results with... 

H H non-bonded interactions are of great importance in organic compoimds, and thus it was of interest to attempt to investigate H H non-bonded potential functions via the determination of a steric isotope effect in the configurational inversion of an unsubstituted biaryl. In view of the extensive work of Harris and her co-workers in the 1,1 -binaphthyl series (see, for example, Badar et al., 1965 Cooke and Harris, 1963), and since the parent compound is one of the simplest hydrocarbons that may be obtained in enantiomeric forms, the determination of the isotope effect in the inversion of l,l -binaphthyl-2,2 -d2 (9) was... 

INVERSE KINETIC ISOTOPE EFFECT STERIC ISOTOPE EFFECT Isotope effects on Aiax/fCn,... 

Stability and reactivity of crown-ether complexes, 17, 279 Stereochemistry, static and dynamic, of alkyl and analogous groups, 25, 1 Stereoelectronic control, the principle of least nuclear motion and the theory of, 24, 113 Stereoselection in elementary steps of organic reactions, 6, 185 Steric isotope effects, experiments on the nature of, 10, 1... 

Steric isotope effects are well documented in the literature of organic chemistry, and have been measured in several reactions in which severe crowding occurs. Mislow and co-workers first demonstrated such effects by determining racemization rates of I, where R = H or D [92], The inverse... 

In AIBN photolysis, as in most solid-state product studies, the reaction was carried out at much higher temperature (200 K), where it is probably safe to assume that steric isotope effects are unimportant. At cryogenic temperatures, however, they should be important whenever strong steric interactions influence the rate of reaction. 

We have observed steric isotope effects at higher temperatures in the transitions between A and B ( 30 K) and between B and C ( 50 K) in mixed crystals of 13C-1-UP and deuterated peroxides. By observing the differences in the rates of these transitions for hosts and guests, we could assess the effect of deuterium in the a and P positions of the radicals themselves. 

Since the radical motions are unlikely to involve changes in bonding, the effects of deuterium in the P positions are almost certainly steric, but the sense of the effect (kH > kD) is opposite the steric isotope effects that are normally observed. Given the standard interpretation of steric isotope effects, which assumes that the transition state survives several periods of normal vibration [98], the present results imply that the smaller size of deuterium reduces the driving force for radical motion. That is, the P methylene group is under more stress in Species A24 than in the transition state leading to the next intermediate structure. 

Mugridge JS, Bergman RG, Raymond KN (2010) The steric isotope effect in a supramolecular host-guest exchange reaction. Angew Chem Int Ed Engl 49(21) 3635-3637... 

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