Kinetics additive effects

In the Sharpless epoxidation of divinylmethanols only one of four possible stereoisomers is selectively formed. In this special case the diastereotopic face selectivity of the Shaipless reagent may result in diastereomeric by-products rather than the enantiomeric one, e.g., for the L -(-(-)-DIPT-catalyzed epoxidation of (E)-a-(l-propenyl)cyclohexaneraethanol to [S(S)-, [R(S)-, [S(R)- and [R(R)-trans]-arate constants is 971 19 6 4 (see above S.L. Schreiber, 1987). This effect may strongly enhance the e.e. in addition to the kinetic resolution effect mentioned above, which finally reduces further the amount of the enantiomer formed. 

Bromination has been shown not to exhibit a primary kinetic isotope effect in the case of benzene, bromobenzene, toluene, or methoxybenzene. There are several examples of substrates which do show significant isotope effects, including substituted anisoles, JV,iV-dimethylanilines, and 1,3,5-trialkylbenzenes. The observation of isotope effects in highly substituted systems seems to be the result of steric factors that can operate in two ways. There may be resistance to the bromine taking up a position coplanar with adjacent substituents in the aromatization step. This would favor return of the ff-complex to reactants. In addition, the steric bulk of several substituents may hinder solvent or other base from assisting in the proton removal. Either factor would allow deprotonation to become rate-controlling. 

If (A i[X ]/A 2[Y ]) is not much smaller than unity, then as the substitution reaction proceeds, the increase in [X ] will increase the denominator of Eq. (8-65), slowing the reaction and causing deviation from simple first-order kinetics. This mass-law or common-ion effect is characteristic of an S l process, although, as already seen, it is not a necessary condition. The common-ion effect (also called external return) occurs only with the common ion and must be distinguished from a general kinetic salt effect, which will operate with any ion. An example is provided by the hydrolysis of triphenylmethyl chloride (trityl chloride) the addition of 0.01 M NaCl decreased the rate by fourfold. The solvolysis rate of diphenylmethyl chloride in 80% aqueous acetone was decreased by LiCl but increased by LiBr. ° The 5 2 mechanism will also yield first-order kinetics in a solvolysis reaction, but it should not be susceptible to a common-ion rate inhibition. 

However, measurements of substituent effects supported the hypothesis that the aryl cation is a key intermediate in dediazoniations, provided that they were interpreted in an appropriate way (Zollinger, 1973a Ehrenson et al., 1973 Swain et al., 1975 a). We will first consider the activation energy and then discuss the influence of substituents, as well as additional data concerning the aryl cation as a metastable intermediate (kinetic isotope effects, influence of water acitivity in hydroxy-de-di-azoniations). Finally, the cases of dediazoniation in which the rate of reaction is first-order with regard to the concentration of the nucleophile will be critically evaluated. 

Important additional evidence for aryl cations as intermediates comes from primary nitrogen and secondary deuterium isotope effects, investigated by Loudon et al. (1973) and by Swain et al. (1975 b, 1975 c). The kinetic isotope effect kH/ki5 measured in the dediazoniation of C6H515N = N in 1% aqueous H2S04 at 25 °C is 1.038, close to the calculated value (1.040-1.045) expected for complete C-N bond cleavage in the transition state. It should be mentioned, however, that a partial or almost complete cleavage of the C — N bond, and therefore a nitrogen isotope effect, is also to be expected for an ANDN-like mechanism, but not for an AN + DN mechanism. 

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... 

In addition to the magnetic differences between the deuteron and proton, however, their mass difference may also cause observable effects. A well known example is found in the theory of chemical reactions, where the so called kinetic isotope effects (KIE s) are an important source of information about reaction mechanisms. Also in the field of ESR, such effects may arise, although these have been much less studied than the KIE s. 

Interest has been shown by several groups on the effect of solvent and of added anions upon the oxidation of alcohols. The oxidation of isopropanol proceeds 2500 times faster in 86.5 % acetic acid than in water at the same hydrogen ion concentration . The kinetics and primary kinetic isotope effect are essentially the same as in water. Addition of chloride ion strongly inhibits the oxidation and the spectrum of chromic acid is modified. The effect of chloride ion was rationalised in terms of the equilibrium,... 

The first term was found to correspond to the rate of enolisation (measured by an NMR study of hydrogen-deuterium exchange at the methylene group). The second term predominates at [Cu(II)] > 10 M and is characterised by a primary kinetic isotope effect of 7.4 (25 °C) and a p value of 1.24. Addition of 2,2 -bipridyl (bipy) caused an increase in 2 up to a bipy Cu(II) ratio of 1 1 but at ratios greater than this 2 fell gradually until the enolisation term dominated. The oxidation of a-methoxyacetophenone is much slower but gives a similar rate... 

Another result of the cold-fusion epopee that was positive for electrochemistry are the advances in the experimental investigation and interpretation of isotope effects in electrochemical kinetics. Additional smdies of isotope effects were conducted in the protium-deuterium-tritium system, which had received a great deal of attention previously now these effects have become an even more powerful tool for work directed at determining the mechanisms of electrode reactions, including work at the molecular level. Strong procedural advances have been possible not only in electrochemistry but also in the other areas. 

Jenner investigated the kinetic pressure effect on some specific Michael and Henry reactions and found that the observed activation volumes of the Michael reaction between nitromethane and methyl vinyl ketone are largely dependent on the magnitude of the electrostriction effect, which is highest in the lanthanide-catalyzed reaction and lowest in the base-catalyzed version. In the latter case, the reverse reaction is insensitive to pressure.52 Recently, Kobayashi and co-workers reported a highly efficient Lewis-acid-catalyzed asymmetric Michael addition in water.53 A variety of unsaturated carbonyl derivatives gave selective Michael additions with a-nitrocycloalkanones in water, at room temperature without any added catalyst or in a very dilute aqueous solution of potassium carbonate (Eq. 10.24).54... 

It is still not clear whether steric constraints can modify the magnitude of bromine bridging. There is at least one example that suggests that this is possible. Non-additive kinetic substituent effects and cis-dibromoadducts imply that the intermediate of cis-cyclooctene bromination in methanol is a /J-bromocarbocation (Dubois and Fresnet, 1974). 

Another interesting lithium-based system is Li3N/Li2NH [53]. Lithium nitride can be hydrogenated to lithium imide and lithium hydride (5.4 wt% H2). The latter reaction can be used for reversible storage at 250°C. The formation of ammonia can be completely avoided by the addition of 1% TiCl3 to the system, which has the positive additional effect to improve the kinetics [54]. Very fast kinetics has been reported for a partially oxidized lithium nitride [55]. 

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. 

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). 

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