Beta-secondary isotope effects

Lin, S., Saunders, W. H. (1994) Tunneling in elimination reactions -structural effects on the secondary beta-tritium isotope effect, J. Am. Chem. Soc. 116, 6107-6110. 

The intramolecular isotope effect reflects zero-point energy differences in the isotopic transition states and also contains a secondary isotope effect contribution as the non-reacting atom at the beta carbon is tritium for and hydrogen for k. The intermolecular isotope effect is independent of the secondary phenomenon in this case. 

The beta-tritium secondary isotope effect for elimination from the propyl-trimethylammonium ion (8, Table 7) seems most probably explained in terms of reduced acidity of the beta hydrogen caused by the greater inductive effect of the bond to the heavier isotope. A hyperconjugative effect also fits the observed data as in the transition state the developing double bond would be more effectively stabilised by the methyl than the monotritiomethyl group. However, the latter explanation seems less likely as the elimination from the propyl compound is slightly slower than that from the ethyl derivative . 

A number of kinetic isotope studies have been reported for gas-phase eliminations. Isopropyl bromide-dg decomposes more slowly than isopropyl bromide and the intramolecular isotope effects (A ,c2D4hx-c2D4)/ (C2D4hx-c2D.iH)) have been recorded for pyrolyses of ethyl acetate (2.0), chloride (2.20), and bromide (2.10) at 500°C. At the elevated reaction temperatures, these values correspond to the maximum predicted for complete loss of the C-H stretching vibration and they have been interpreted as indicating considerable weakening of the C-H bond in the transition state. Whether this is a homolytic or hetero-lytic bond fission, it is remarkably insensitive to beta substituent effects on rate. The intramolecular isotope effects in these cases could reflect predominantly a secondary isotope effect rather than the intended primary effect and dissection into an intermolecular and secondary isotope effect would prove more fruitful. (Section 2.2.1.)... 

Mechanistically, radical polymerizah ons are addition polymerizations, and they follow the exact same radical chain process discussed in Chapters 10 and 11. The key steps of initiation, propagation, and termination are again involved, as recapitulated in Figme 13.13 B. Based upon studies of substituents on the carbon beta to the site of radical addition, it has been concluded that the adding radical has almost completely formed a bond at the transition state. Secondary isotope effects support this notion of a late transition state, with values between 1.05 to 1.17 for deuterium at the site beta to addition. 

Secondary hydrogen kinetic isotope effects are further classified as alpha, beta, etc. depending on the distance of the isotopically substituted atom from the bond(s) that is (are) being made or broken (a = 1 bond, 3 = 2 bonds, etc.). Consider the simple Sn2 reaction between hypochlorite anion and ethyl chloride ... 

WA Garland, SD Nelson, HA Sasame. Primary and beta-secondary deuterium isotope effects in the O-deethylation of phenacetin. Biochem Biophys Res Commun 72 539—545, 1976. 

Despite practical difficulties, tritium tracers can be used to dissect the various isotope effects which are incorporated in the direct rate comparisons for substrates having secondary or primary beta carbon. The requisite rate coefficients in reaction (66) can be calculated from a knowledge of the mole fraction reacted (/), the molar activity of the reactant (M,) and the product Mi) at that time, and the initial molar activity (Mo) of the reactant (67, 68) - ... 

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