Solvents deuterium isotope effects

For this type of reaction the value of the solvent deuterium isotope effect is often a conclusive argument for the proposed mechanism 16). Rate measurements of 1 in acetic acid-acetate buffers in light and heavy water resulted in an isotope effect ktiiO lkozo of 2.5, and A oac/ doac of 9. A ratedetermining proton transfer to the /3-carbon atom of the enamine has been proposed and accounts for the experimental results I6-18 Eq. (5). 

The solvent deuterium isotope effect for hydration of 4a and CH3C=C-0CH=CHCH3 were A Hjo/ DjO =2.13 and h o/ DjO" 1-90, respectively (8, 6). No deuterium was incorporated at the acetylenic position in 4a when this compound was reisolated after partial hydration in D2 O. 

Solvent Deuterium Isotope Effects for the Hydration of Phenylacetylenes at 25° ... 

The rates of hydration of substituted phenylpropiolic acids give a rho of —4.77 when plotted against a, comparable to Ihe acid-catalyzed isomerization of czs-cinnamic acid, with a rho value of —4.3. The solvent deuterium isotope effects are 3.7-S.2 for the isomerization of cinnamic acids at... 

The acid catalysed denitrosation of N-nitrosamides is subject to a substantial solvent deuterium isotope effect [k (H)/k (D)... 

This all seemed very reasonable at the time, but subsequent work was not consistent with it. A small but measurable amount of 180 exchange was reported for some amides in reasonably concentrated HC1 media,277,278 and for at least one amide the amount of exchange decreased with increasing acidity,277 which is the opposite of what would be expected with the Scheme 14 one-water-molecule mechanism taking over from the equation (74) three-water-molecule mechanism as the acidity increased. Also, the solvent deuterium isotope effect was found to be close to unity for at least one amide,278 a result that has since been confirmed,279 which is not what would be expected on the basis of either a three- or a one-water-molecule process.280 Because of this it was decided to reexamine the lactam hydrolysis data subsequent to the publication of the excess acidity analysis of the H NMR results for these,268 a new study appeared with rate constant data for four of these molecules in aqueous H2S04 media obtained by UV spectroscopy at several temperatures,281 and this was included too.282... 

The observation of a primary solvent deuterium isotope effect (kH/fa>) = 2-4 on the specific acid-catalyzed hydrolysis of vinyl ethers provides evidence for reaction by rate-determining protonation of the alkene.69 Values of kHikD 1 are expected if alkene hydration proceeds by rate-determining addition of solvent to an oxocarbenium ion intermediate, since there is no motion of a solvent hydron at the transition state for this step. However, in the latter case, determination of the solvent isotope effect on the reaction of the fully protonated substrate is complicated by the competing exchange of deuterium from solvent into substrate (see above). 

At low hydroxide-ion concentrations, the rate of approach to equilibrium after a temperature jump decreases as the hydroxide-ion concentration increases. At higher concentrations the reaction becomes first order in hydroxide ion. The value of the kinetic solvent deuterium isotope effect on the reaction shows little variation over the range of hydroxide-ion concentrations studied as shown in Fig. 19. The ratio t-1(H20)/t 1(D20) at a particular concentration of OL (L = H or D) remains within the range 2.0 to 3.0 for OL" concentrations of 0.001 to 0.100 mol dm - 3 and provides little mechanistic information. Similar results were obtained in the original work (Perlmutter-Hayman and Shinar, 1978). 

In contrast, the acid-catalyzed hydrolysis of alkyl selenates is A-2158. The actual species which undergoes decomposition to alcohol and sulfur trioxide is probably the zwitterion as in the case of phosphate monoester monoanions. Evidence for sulfur trioxide as the reactive initial product of the A-1 solvolysis is obtained from the product compositions arising with mixed alcohol-water solvents. The product distribution is identical to that found for sulfur trioxide solvolysis, with the latter exhibiting a three-fold selectivity for methanol. Although the above entropies of activation and solvent deuterium isotope effects do not distinguish between the conventional A-l mechanism and one involving rate-limiting proton transfer, a simple calculation, based on the pKa of the sulfate moiety and the fact that its deprotonation is diffusion controlled. 

The rates of spontaneous hydrolysis of aryl a-disulfones and aryl sulfinyl sulfones in dioxan-water are similar in their response to reaction variables solvent composition, electronic effects (p = +3.5), activation parameters and solvent deuterium isotope effects AfeoMuio = 2.3,BS. The difference in rate (the aryl a-disulfone hydrolyzing some 10,000 times more slowly) is principally the result of a more unfavorable energy of activation and not a change in... 

Recently, Noyce and Pollack306 have found kinetic evidence for a changeover from acyl to alkyl-oxygen cleavage in the hydrolysis of a-acetoxystyrenes. At low acidities (1 M H2S04) compounds with electron-withdrawing substituents are hydrolyzed in a reaction which behaves as expected for the Aac2 mechanism. The solvent deuterium isotope effect, kH/kD = 0.75, and the effect of substituents on the rate is small. As the acidity of the medium is increased... 

The experimental evidence that these reactions do, in fact, represent general base catalysis, rather than nucleophilic catalysis of hydrolysis, is very strong. The solvent deuterium isotope effect of 2-3 (Table 39) is consistent with the breaking of a bond to hydrogen in the rate-determining step of the reaction ... 

The very small solvent deuterium isotope effect in this case is consistent with nucleophilic catalysis, which would anyway be expected because of the high basicity of cyanide. 

The kinetics of hydrolysis of N-salicylidene-2-aminothiazole (119 = HL) have been studied in aqueous 5% methanol in the presence and absence of Co11, Ni, Cu11 and Zn11.408 The solvent deuterium isotope effect on the rate of spontaneous and hydroxide-catalyzed hydrolysis of the Schiff-base anion (L ) is consistent with intramolecular catalysis by the phenoxide ion. Only... 

The solvent deuterium isotope effect in the reaction of 359 with glyoxylate decreases from ( H2o/ D2o) °f 1-66 to ( H2o/ D2o) °f 1-12 with increasing pH from 1.25 to 6.43, respectively. 361 probably decarboxylates via a cyclic transition state. Transfer of the carboxylic proton takes place simultaneously with heavy-atom reorganization as indicated by small solvent DIE in the acid-catalysed reaction. The solvent DIE h2o/ D20 °f 1-20 at 1. M H+, observed in the reaction of 359 with pyruvic acid, is similar to the reaction of pyruvic acid with nitrosobenzene for which nucleophilic attack of nitroso nitrogen has been proposed395. 

Cis- and trans-440 with base yield 1,4-diphenylbutan-l-one, 441. In D2O the product incorporates one deuteron at C(4) and varying amounts of deuterium at the enolizable 2-position507 (equation 263). The inverse solvent deuterium isotope effect (kn2o/kD2o = 0.68) and the discrimination isotope effect (k /k ) = 0.99 0.05)508 support a reaction scheme, in which the alkoxide reacts in the RDS to yield a benzylic anion 442, which in turn yields the deuteriated product 441 (equation 263). 

Application of the extended Grunwald-Winstein equation to solvolyses of propyl chloroformate, PrOCOCl, in a variety of pure and binary solvents indicated an addition-elimination pathway in the majority of the solvents but an ionization pathway in the solvents of highest ionizing power and lowest nucleophilicity. For methanolysis, a solvent deuterium isotope effect of 2.17 was compatible with the incorporation of general-base catalysis into the substitution process.21... 

Very different solvent deuterium isotope effects (SDIE) of (/ch)/( d) = 0.42 and 1.66, respectively, are observed for acid-catalyzed addition of solvent to o-l and 81.50,58 The inverse SDIE for hydration of o-1 is consistent with initial fast and reversible protonation of substrate followed by rate-determining addition of solvent to the protonated benzylic carbocation o-H-l +. The normal primary SDIE on acid-catalyzed hydration of 81 is consistent with a change in mechanism from stepwise, for acid-catalyzed addition of water o-l,50 to concerted for the acid-catalyzed reaction of 81, where the addition of water and hydron occurs at a single reaction stage (kcon, Scheme 47). 

Faraci and Walsh263 studied the substrate and solvent deuterium isotope effects of the reactions catalyzed by alanine racemases of S. typhimurium (DadB and Air enzymes) and B. stearothermophilus. Although the kinetic constants for all three alanine racemases obey the Haldane equation, i.e., Keq= 1 (this confirms that the enzymes are true racemases), the individual Micaelis-Menten parameters in both directions show marked difference in the binding of each isomer. This suggests a structural asymmetry at the active sites of these enzymes. The asymmetry in the recognition and turnover of substrate enantiomer was also clearly seen in the results of isotope effect experiment with DadB enzyme. In the d-... 

Experiments on solvent deuterium isotope effect with L-tryptophan and S-methyl-L-... 

Figure 19. Products and solvent deuterium-isotope effect (see...

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