Solvent deuterium KIE

Transition-state analysis has been reported for acid-catalysed hydrolysis of the enol ether functionality of enol pyruvylshikimate 3-phosphate for which rate-determining C(3) protonation precedes attack of H2O 2- " C, 3- " C, 3,3- H2, and solvent deuterium KIEs have been discussed." " ... 

The effect of a change in solvent on the secondary a-deuterium KIEs 195 Secondary a-deuterium KIEs and the effect of ionic strength on transition state structure 197... 

For instance, (kH/kD)a was 1.085 0.011 when the sodium thiophenoxide concentration was 0.0086 mol dm-3 and 1.129 0.010 when the concentration of the sodium thiophenoxide was reduced to 0.0040 mol dm-3 in DMF at 20°C. Conductivity and UV studies of sodium thiophenoxide solutions in DMF, in DMSO, in methanol and in diglyme, and reactions done in the presence of the macrocyclic polyether 15-crown-5 (Westaway and Lai, 1988), showed that the change in the secondary a-deuterium KIE was due to a change in the form of the reacting nucleophile from a solvent-separated ion-pair complex at the higher concentration (see (27)) to a free ion at the lower concentration. 

Table 26 The secondary a-deuterium KIEs for the SN2 reactions between butyl chloride and thiophenoxide ion when the nucleophile is a contact ion-pair, a solvent-separated ion-pair complex and a free ion at 200C.0...

THE EFFECT OF A CHANGE IN SOLVENT ON THE SECONDARY a-DEUTERIUM KIEs... 

Kluger and Brandi (1986b) also studied the decarboxylation and base-catalysed elimination reactions of lactylthiamin, the adduct of pyruvate and thiamin (Scheme 2). These reactions are nonenzymic models for reactions of the intermediates formed during the reaction catalysed by the enzyme pyruvate decarboxylase. The secondary j3-deuterium KIE for the decarboxylation was found to be 1.09 at pH 3.8 in 0.5 mol dm-3 sodium acetate at 25°C. In the less polar medium, 38% ethanolic aqueous sodium acetate, chosen to mimic the nonpolar reactive site in the enzyme, the reaction is significantly faster but the KIE was, within experimental error, identical to the KIE found in water. This clearly demonstrates that the stabilization of the transition state by hyperconjugation is unaffected by the change in solvent. 

Ab initio MO calculations were carried out on the hydrolysis of CH3CI, with explicit consideration of up to 13 water solvent molecules. The treatments were at the HF/3-21G,HF/6-31G,HF/6-31 G orMP2/6-31 G levels. Forn > 3 three important stationary points were detected in the course of the reaction. Calculations for n = 13 at the HF/6-31 G level reproduced the experimental activation enthalpy and the secondary deuterium KIE. The proton transfer from the attacking water to the water cluster occurs after the transition state, in which O-C is 1.975 A and C-Cl is 2.500 A. 

Deuterium KIE in the reaction of 3-metyl-l-butene, 378, with CF3COOH-D (TFA-D), providing 3-methyl and 2-methylbutyl trifluoroacetate, 389, in about 53 47 ratio both in TFA-H and in TFA-D, was 6.8 (at 26.5 °C)434. In the similar reaction with 2-methyl-l-butene 379, and 2-methyl-2-butene, 380, with TFA-D, the D KIEs have been found434 to be 5 (379, —18 °C). and 3.9 (380, —18 °C). 378 reacts by carbocationic mechanism and undergoes a Me shift. Extensive H/D exchange between the solvent and the ester 381 took place. 

The deuterium KIE in the nitrile-forming elimination of 467 (equation 275), promoted by Et3N-MeCN, t-BuOK-t-BuOH-and t-BuOK-DMSO, has been found533 to be dependent on the base-solvent variation from t-Bu-OH to DMSO. 

Finally, strong solvation of the carbenium ion intermediate also causes a marked reduction in secondary (5-deuterium KIE.84 For example, the (5-deuterium KIE in the solvolysis of isopropyl tosylate is reduced from 1.13/(5-D in trifluoroethanol, which does not solvate the developing carbenium ion strongly, to 1.08/ p-D in water where the carbenium ion is strongly solvated. Again, hyperconjugation is reduced because the solvent stabilizes the developing carbenium ion in the transition state. 

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