Deuterium solvent kinetic isotope effects

An examination of the deuterium solvent kinetic isotope effects (SKIEs) for the reactions with (l)Feffl(X)2 and (2)Fe (X)2 show that the SKIEs values are comparable for alkyl hydroperoxides and hydrogenperoxide. Moreover, the SKIEs for the decomposition of IH2 (k lk P) display values that are >2 and <3, while the values for the decomposition of IIH ( k4 lk4 ) are - l.O. This establishes that the decomposition of IIH2 at low pH represents general-base catalysis with water solvent as the catalyst. In contrast, the reactions at intermediate pH (i.e., IIH decomposition) are not subject to such catalysis. Recall that 4-substituted 2,6-dimethylpyridines act as general base catalysts in the decomposition of IIH2 . 

Solvent isotope effects. Much mechanistic information can be obtained about reactions involving proton transfer from solvent kinetic isotope effects, particularly in solvents of mixed isotopic composition. For practical reasons work is essentially confined to H/D effects, especially those in water. Unlike ordinary primary hydrogen isotope effects, solvent isotope effects have to take into account a host of exchangeable sites, subject to equilibrium as well as kinetic isotope effects. A key concept is that of the fractionation factor, (p, which is the deuterium occupancy of a site in a 1 1 H2O/D2O mixture more formally it is defined by equation l.l ... 

Supportive of the suggestion that ionization is not a major pathway in the Claisen rearrangement of the parent compound is the fact that the SDKIEs in aqueous solution are comparable to those in the gas phase and in m-xylene. Furthermore, attempts to solvolyze 1,1-dideuterioaUyl mesylate in aqueous methanol resulted in no ionization to an allyl cation instead, the direct displacement product was formed exclusively. Finally, determinations of a solvent kinetic isotope effect in deuterium oxide resulted in values around unity 10%. ° In the solvolysis reaction of tert-butyl chloride the value is 40% at room temperature. " It is possible to cause allylvinyl ethers to ionize by providing cation stabilizing substituents and Lewis acids or Lewis acidic solvents. ... 

Interpreting solvent kinetic isotope effects in terms of these interactions can provide information about the transition structure, its solvation, or both. With one technique, known as the proton inventory technique, the rate of a reaction is studied in a series of mixtures of H2O and D2O. The isotope effect, / H20/ is plotted versus the parameter n, the mole fraction of deuterium in the solvent. The slope and curvature of the resulting plot are then analyzed for information about the number and role of solvent molecules involved in the rate-limiting step. ° ... 

It is clear from the results that there is no kinetic isotope effect when deuterium is substituted for hydrogen in various positions in hydrazobenzene and 1,1 -hydrazonaphthalene. This means that the final removal of hydrogen ions from the aromatic rings (which is assisted either by the solvent or anionic base) in a positively charged intermediate or in a concerted process, is not rate-determining (cf. most electrophilic aromatic substitution reactions47). The product distribution... 

A second reason for the larger isotope effect observed by Jones and Maness (140) might be that in the less polar acetic acid solvent, there might be a small degree of E2 elimination (with solvent acting as base) superimposed on the dominant Sn 1 mechanism. Such an elimination would involve a primary kinetic deuterium isotope effect with a kn/ko s 2 to 6, and hence even a 1 to 5% contribution from such a pathway would have a significant effect on the experimentally observed kinetic isotope effect. 

Kelley and co-workers [70, 71] measured the dynamics of the excited-state intramolecular proton transfer in 3-hydroxyflavone and a series of its derivatives as a function of solvent (Scheme 2.9). The energy changes associated with the processes examined are of the order of 3 kcal/mol or less. The model they employed in the analysis of the reaction dynamics was based upon a tunneling reaction path. Interestingly, they find little or no deuterium kinetic isotope effect, which would appear to be inconsistent with tunneling theories. For 3-hydroxy-flavone, they suggest the lack of an isotope effect is due to a very large... 

The nucleophile in the S.v2 reactions between benzyldimethylphenylammonium nitrate and sodium para-substituted thiophenoxides in methanol at 20 °C (equation 42) can exist as a free thiophenoxide ion or as a solvent-separated ion-pair complex (equation 43)62,63. The secondary alpha deuterium and primary leaving group nitrogen kinetic isotope effects for these Sjv2 reactions were determined to learn how a substituent on the nucleophile affects the structure of the S.v2 transition state for the free ion and ion-pair reactions64. 

The electrophile E+ attacks the unhindered side of the still unsubstituted second aromatic ring. A proton (deuteron) is transferred from this ring to the second, originally substituted ring, from which it leaves the molecule. Thus, the electrophile enters, and the proton (deuteron) leaves the [2.2]paracyclophane system by the least hindered paths. Some migration of deuterium could be detected in the bromination of 4-methyl[2.2]paracyclophane (79). The proposed mechanism is supported by the kinetic isotope effects ( h/ d) found for bromination of p-protio and p-deuterio-4-methyl[2.2]paracyclophanes in various solvents these isotope effects demonstrate that proton loss from the a complex is the slowest step. 

The only kinetic isotope effects so far reported for these reactions are those given by Pocker (1960), without experimental detail. He reports closely similar values for the rates of solvent-catalysed hydration of the species CHg. CHO, CD3. CHO, CH3. CDO and CD3. CDO in water at 0° C the replacement of CH3 by OD3 increases the velocity by about 7%. The same effect is reported for solutions in deuterium oxide at 0° C, presumably super-cooled. A comparison was also made of rates of hydration in HjO and DgO at 0°C, giving the following values for k(H.z0)lk(T>20) in presence of different catalysts H+/D+, 1 -3 AcOH/AcOD, 2 5 AcO , 2-3 H2O/D2O, 3-6. Almost exactly the same ratios were obtained by measuring rates of dehydration at 25° C in dioxan containing 10% of H2O or D2O and various catalysts. The presence of a considerable solvent isotope effect is consistent with the mechanism given in Section IV,B, and it would not be expected that substitution of deuterium on carbon would have an appreciable effect on the rate. 

Hydrogen abstraction from propan-2-ol and propan-2-ol- /7 by hydrogen and deuterium atoms has been studied by pulsed radiolysis FT-ESR. A secondary kinetic isotope effect was observed for H (D ) abstraction from the C—H (C—D) bonds. The results were compared with ab initio data. In similar work, the kinetic isotope effects in H and D abstraction from a variety of other alcohols in aqueous solvents have been measured. It was found that, compared with the gas phase, the reactions exhibit higher activation energies in agreement with the ability of solvation to decrease the dipole moment from the reactant alcohol to the transition state. 

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