Isotope effects primary, tautomerization

Nuclear tunnelling in the aqueous iron (2+)-iron (3+) electron transfer has been investigated467 and the rate enhancement for H2O has been assessed to be 65 times the classical rate, and that for D2O 25 times the classical rate, yielding a H/D isotope effect of 2.6. The occurrence of the general base catalysis and sizable primary D KIEs indicated that the isomerization of l//-indene-l-carboxylic acid to l//-indene-3-carboxylic acid in aqueous solution takes place through an enolization-reketonization sequence468. Kinetic HH/HD/DD isotope and solvent effects have been used in a dynamic NMR study469 of the tautomerization of 15N-and 2H -labelled bicyclic oxalamidines. 

Magnesium bis(hexamethyldisilazide), Mg(HMDS)2, catalyses the enolization of ketones.287 On addition to propiophenone in toluene at ambient temperature, a ca 3 1 E Z mixture of enolates (103, R=SiMe3) is formed. These enolates, and an initial ketone complex, have been characterized by NMR, X-ray, IR, and UV-visible spectroscopy and computational studies. Kinetics of tautomerization have been measured, with proton transfer confirmed as rate determining ( hAd = 18.9 at 295 K). The significant temperature dependence of the primary isotope effect is indicative of tunnelling. 

A kinetic isotope effect would favour the tautomerization 40 - 41 and consequently the elimination of CH30//. Because independent of the lifetime only CH3OZ) is eliminated, one has to exclude 40 as a reactive intermediate in the primary fragmentation steps (8). 

Primary deuterium isotope effects have also been measured in 8-hydroxyquinoline N-oxides (32) . It was found that a plot of A( H, H) vs. 50H had a different slope than observed for tautomeric hydroxyquinones and /3-diketones . 

The only isotope effects which are usually of significance in electroorganic mechanism considerations are those involving H and D in (a) primary kinetic isotope effects, (b) secondary solvent isotope effects where reactions are compared in pure H2O and D2O or pure h- and rf-alcohols, and (c) in prior protonation equilibria, e.g., with ketone reduction. Primary kinetic isotope effects having a magnitude of > 2.5 may be expected in reactions that involve a rearrangement with proton participation, e.g., keto-enol tautomerism prior to an electron transfer step. Most other H/D isotope effects arise from protonation equilibria prior to the rate-controlling electron transfer step (e.g., in ketone reduction RR CO + RR COH ) and the isotope effect is... 

Hansen (1983) has reviewed a number of primary deuterium isotope effects in other tautomeric systems and only some recent examples are given here. 

The primary isotope effects used in the study of tautomeric equilibria are primarily those of deuterium or tritium. As these are proportional [51], they can be used interchangeably as long as one remembers that they should be scaled. Primary deuterium isotope effects in hydrogen-bonded nontautomeric systems are found to correlate with the OH chemical shifts in a nonhnear manner. This is illustrated in Figure 6.25. 

Schiff bases are important molecules also in biological contexts. Schifif bases of ortho-hydroxy type (Figure 6.26) represent both static and tautomeric cases. Primary deuterium isotope effects are small in a static case. For tautomeric systems, the primary deuterium isotope effects on chemical shifts are temperature dependent [50]. This was also investigated in detail for a series of Schiff bases (X = 4-methoxy, 5-methoxy, and 4,6-dimethoxyphenyl of Figure 6.26). These have been studied in detail using secondary isotope effects on chemical shifts. One approach is the simple one presented in Eq. (6.1). The other one is based on the Limbach approach [40]. The presence of an equilibrium is established in many of these Schiff bases. A... 

The primary tritium and deuterium isotope effects were found to be 0.91 and 0.62 ppm, respectively, again suggesting either a very strong hydrogen bond or a tautomeric equihbrium. 

As seen in Figure 3.24 a plot of secondary deuterium isotope effects on chemical shifts versus primary deuterium chemical shifts clearly reveal which compounds are tautomeric. 

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