Hydrogen atom transfers, isotope effects

Lewis, E. S. Isotope Effects in Hydrogen Atom Transfer Reactions. 74, 31-44 (1978). 

The mechanistic proposal of rate-limiting hydrogen atom transfer and radical recombination is based on the observed rate law, the lack of influence of CO pressure, kinetic isotope effects [studied with DMn(CO)s] and CIDNP evidence. In all known cases, exclusive formation of the overall 1,4-addition product has been observed for reaction of butadiene, isoprene and 2,3-dimethyl-l,3-butadiene. The preferred trapping of allyl radicals at the less substituted side by other radicals has actually been so convincing that its observation has been taken as a mechanistic probe78. 

There have been numerous kinetic studies of the deuterium isotope effect for proton and hydrogen atom transfer where values for EH — Ev greatly exceed 1.4kcal/mol and the ratio of A factors, AD/AH, are significantly >1.4 values >10 are very common [4]. These observations directly challenge the classical model for proton transfer based upon transition state theory that neglects contributions from k. 

It may be concluded that for reactions where the proton is less or more than one-half transferred in the transition state, i.e. the A—H and H—B force constants are unequal, the primary hydrogen-deuterium kinetic isotope effect will be less than the maximum of seven. The maximum isotope effect will be observed only when the proton is exactly half-way between A and B in the transition state. This relationship is also found for carbon kinetic isotope effects where the isotopically labelled carbon is transferred between two atoms in the reaction10,11. This makes interpreting carbon isotope effects difficult. 

Shorthand notations such as ET (electron transfer), HAT (hydrogen atom transfer), BDE (bond dissociation energy), NHE (normal hydrogen electrode), CV (cyclic voltammetry), LFP (laser flash photolysis), EPR (electron paramagnetic resonance) and KIE (kinetic isotope effect) will be used throughout the chapter. In addition, recurring chemical compounds such as TEMPO (2,2,6,6-tetramethylpiperidine-Ai-oxyl), HBT (1-hydroxyben-zotriazole), BTNO (benzotriazole-A-oxyl), HPI (iV-hydroxyphthalimide), PINO (phthal-imide-iV-oxyl), NHA (A-hydroxyacetanilide) and a few others will be referred to by means of the capital-letter acronym. 

Participation of the hydride-formyl equilibrium in (16) is also plausible in light of an apparent inverse kinetic deuterium isotope effect for the catalytic process. Use of deuterium gas instead of hydrogen (cf. Expts. 6 and 4 in Table II) causes an increased rate, with kH/k = 0.73 (37). The existence of an isotope effect implies that hydrogen atom transfer occurs before or during the rate-determining step, and an inverse kinetic isotope effect may be possible in the case of a highly endothermic, product-like transition state (73). On the other hand, Bell has concluded that inverse kinetic isotope... 

The combination of small but significant inverse deuterium and normal 13C KIEs at Cl indicate the bond formation to this carbon atom in the early ratedetermining transition state. The observed hydrogen and carbon isotope effects in position 3 are consistent with proton transfer in the rate-determining step. Thus, from the qualitative analysis of isotope effect an early concerted pericyclic transition state can be concluded. The more detailed structure of transition state was described on the basis of theoretical calculations (Beck-e3LYP/6-31G ). 

If we consider the hydrogen atom transfer as successive transfer of proton and electron, the kinetic isotope effect requires the proton transfer step to be rate determining.2 This assumption, together with the negative p values found experimentally, implies that the electron moves somewhat ahead of the more slowly moving proton (Ingold, 1967). 

Isotope Effects in Hydrogen Atom Transfer Reactions... 

It is always tempting to try to fit observed quantities into a theoretical framework, no matter how simple and crude. One obstacle to such an attempt is the prevalence of experimental error. A discussion of experimental methods for the study of isotope effects in hydrogen atom transfers including some common errors, has been presented elsewhere11 and will not be repeated. This reference also contains many of the experimental values on which the following discussion is based. 

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