Hydrogen/deuterium reaction with kinetic isotope effect

The reactions of A-phenyl a-r-butyl nitrone (PEN) with maleimides, maleic anhydride, and diethyl maleate have been studied by EPR and two types of spin adduct detected. They arise from the reductive addition of PEN to the alkenes and the degradation product of DEN (2-methyl-2-nitropropane). The deuterium and muonium kinetic isotope effects for the addition of the hydrogen atom to a variety of alkenes have been determined experimentally and theoretically. ... 

Large hydrogen isotope effects were found experimentally very soon after the discovery of deuterium in 1932, and there is now an extensive literature on the subject, recently supplemented by work with tritium. Much of this relates to the kinetics of reactions involving proton transfer, but there is also a large amount of information on acid-base equilibria. A recent review estimated that about 300 papers on isotope effects are now published each year, and a considerable proportion of these relate to the isotopes of hydrogen. The present chapter will be devoted to the effect of isotope substitution on acid-base equilibrium constants, while Chapter 12 will deal with kinetic isotope effects in proton transfer reactions. 

When one of the ortho hydrogens is replaced by deuterium, the rate drops from 1.53 X 10 " s to 1.38 X lO s. What is the kinetic isotope effect The product from such a reaction contains 60% of the original deuterium. Give a mechanism for this reaction that is consistent with both the kinetic isotope effect and the deuterium retention data. 

The deuterium kinetic isotope effect between BH3-THF and BD3-THF was obtained by measuring the reaction rate constants of the two reactions with the unsaturated sulfoxide (Sj-40 independently via React-IR. The k(BH3)/k(BD3) is 1.4, consistent with hydrogen transfer not being the rate-limiting step [15, 16]. 

Three mechanisms have been proposed for this reaction (Scheme 21). The reaction is first order in each of the reactants. In another study, Reutov and coworkers159 found a large primary hydrogen-deuterium kinetic isotope effect of 3.8 for the reaction of tri-(para-methylphenyl)methyl carbocation with tetrabutyltin. This isotope effect clearly demonstrates that the hydride ion is transferred in the slow step of the reaction. This means that the first step must be rate-determining if the reaction proceeds by either of the stepwise mechanisms in Scheme 21. The primary hydrogen-deuterium kinetic isotope effect is, of course, consistent with the concerted mechanism shown in Scheme 21. 

The results from these experiments also allowed Hannon and Traylor to determine the primary and secondary hydrogen deuterium kinetic isotope effects for the hydride abstraction reaction. If one assumes that there is no kinetic isotope effect associated with the formation of 3-deutero-l-butene, i.e. that CH2=CHCHDCH3 is formed at the same rate (k ) from both the deuterated and undeuterated substrate (Scheme 25), then one can obtain both the primary (where a deuteride ion is abstracted) and the secondary deuterium... 

Song and Beak161 have used intramolecular and intermolecular hydrogen-deuterium kinetic isotope effects to investigate the mechanism of the tin tetrachloride catalysed ene-carbonyl enophile addition reaction between diethyloxomalonate and methylenecy-clohexane (equation 105). These ene reactions with carbonyl enophiles can occur by a concerted (equation 106) or a stepwise mechanism (equation 107), where the formation of the intermediate is either fast and reversible and the second step is slow k- > k-i), or where the formation of the intermediate (the k step) is rate-determining. 

Song and Beak found intramolecular and intermolecular hydrogen-deuterium kinetic isotope effects of 1.1 0.2 and 1.2 0.1, respectively, for the tin tetrachloride catalysed ene reaction. Since significant intramolecular and intermolecular primary deuterium kinetic isotope effects of between two and three have been found for other concerted ene addition reactions161, the tin-catalysed reaction must proceed by the stepwise pathway with the k rate determining step (equation 107). 

Abeywickrema and Beckwith162 have measured the primary hydrogen-deuterium kinetic isotope effect for the reaction between an aryl radical and tributyltin hydride. The actual isotope effect was determined by reacting tributyltin hydride and deuteride with the ort/ro-alkcnylphcnyl radical generated from 2-(3-butenyl)bromobenzene (equation 111). 

The exo and the endo ring closures (the kc reactions) are in competition with the aryl radical-tributyltin hydride transfer (the ks or ku reaction). These workers162 used this competition to determine the primary hydrogen-deuterium kinetic isotope effect in the hydride transfer reaction between the aryl radical and tributyltin hydride and deuteride. 

This method gave a primary hydrogen-deuterium kinetic isotope effect of 1.3 for the reaction between the aryl radical and tributyltin hydride. This isotope effect is smaller than the isotope effect of 1.9 which San Filippo and coworkers reported for the reaction between the less reactive alkyl radicals and tributyltin hydride163 (vide infra). The smaller isotope effect of 1.3 in the aryl radical reaction is reasonable, because an earlier transition state with less hydrogen transfer, and therefore a smaller isotope effect164, should be observed for the reaction with the more reactive aryl radicals. 

In one study, Ingold and coworkers166 measured the rate constants for the reactions of several alkyl radicals with tributyltin hydride using a laser flash photolytic technique and direct observation of the tributyltin radical. They also used this technique with tributyltin deuteride to determine the primary hydrogen-deuterium kinetic isotope effects for three of these reactions. The isotope effects were 1.9 for reaction of the ethyl radical, and 2.3 for reaction of the methyl and n -butyl radicals with tributyltin hydride at 300 K. 

Other primary hydrogen-deuterium kinetic isotope effects have been measured for radical reactions with tributyltin hydride. For example, Carlsson and Ingold167 found primary hydrogen-deuterium kinetic isotope effects of 2.7 and 2.8, respectively, for the... 

TABLE 10. The primary hydrogen-deuterium kinetic isotope effects for the reactions of a series of para-substituted benzyl radicals with tributyltin hydride3... 

Finally, Franz and coworkers171 measured the rate constants and primary hydrogen-deuterium kinetic isotope effects for the radical reactions between tributyltin hydride and the neophyl and the 2-allylbenzyl radical in diphenyl ether. The isotope effect in the first reaction was 1.64 at 192.5 °C and that in the second reaction was 1.91 at 236 °C. These values compare well with those predicted from Kozuka and Lewis s primary... 

Several monographs2-5 have detailed discussions dealing with heavy-atom and primary and secondary hydrogen-deuterium kinetic isotope effects. The monograph by Melander and Saunders5 covers the entire area particularly well. For this reason, only a brief summary of the theory of kinetic isotope effects as well as their important uses in the determination of reaction mechanism and transition-state geometry will be presented. 

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