Solvents solvent isotopic effect

The term solvent isotope effect is used in discussions of equilibrium processes in normal and heavy water for the isotope effect, which is attributed to isotopic substitution of the solvent. Solvent isotope effects may be due primary to differences in the structure constructed by the two isotopic water molecules. 

The details of proton-transfer processes can also be probed by examination of solvent isotope effects, for example, by comparing the rates of a reaction in H2O versus D2O. The solvent isotope effect can be either normal or inverse, depending on the nature of the proton-transfer process in the reaction mechanism. D3O+ is a stronger acid than H3O+. As a result, reactants in D2O solution are somewhat more extensively protonated than in H2O at identical acid concentration. A reaction that involves a rapid equilibrium protonation will proceed faster in D2O than in H2O because of the higher concentration of the protonated reactant. On the other hand, if proton transfer is part of the rate-determining step, the reaction will be faster in H2O than in D2O because of the normal primary kinetic isotope effect of the type considered in Section 4.5. 

Alkenes lacking phenyl substituents appear to react by a similar mechanism. Both the observation of general acid catalysis and the kinetic evidence of a solvent isotope effect are consistent with rate-limiting protonation with simple alkenes such as 2-metlQ lpropene and 2,3-dimethyl-2-butene. 

The kinetic features of this reaction, including the solvent isotope effect, are consistent with a rate-determining protonation to form a vinyl cation. ... 

The second-order rate constants for hydration and the kinetic solvent isotope effect for hydration of several 2-substituted 1,3-butadienes ate given below. Discuss the information these data provide about the hydration mechanism. 

Solvent isotope effects are usually in the range / h20+ = 2-3. These values reflect the greater equilibrium acidity of deuterated acids (Section 4.5) and indicate that the initial protonation is a fast preequilibrium. 

The second step in acetal and ketal hydrolysis is conversion of the hemiacetal or hemiketal to the carbonyl compound. The mechanism of this step is similar to that of the first step. Usually, the second step is faster than the initial one. Hammett a p plots and solvent isotope effects both indicate that the transition state has less cationic character than... 

In analyzing the behavior of these types of tetrahedral intermediates, it should be kept in mind that proton-transfer reactions are usually fast relative to other steps. This circumstance permits the possibility that a minor species in equilibrium with the major species may be the major intermediate. Detailed studies of kinetics, solvent isotope effects, and the nature of catalysis are the best tools for investigating the various possibilities. 

This variation from the ester hydrolysis mechanism also reflects the poorer leaving ability of amide ions as compared to alkoxide ions. The evidence for the involvement of the dianion comes from kinetic studies and from solvent isotope effects, which suggest that a rate-limiting proton transfer is involved. The reaction is also higher than first-order in hydroxide ion under these circumstances, which is consistent with the dianion mechanism. 

Values of kH olki3. o tend to fall in the range 0.5 to 6. The direction of the effect, whether normal or inverse, can often be accounted for by combining a model of the transition state with vibrational frequencies, although quantitative calculation is not reliable. Because of the difficulty in applying rigorous theory to the solvent isotope effect, a phenomenological approach has been developed. We define <[), to be the ratio of D to H in site 1 of a reactant relative to the ratio of D to H in a solvent site. That is. 

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). 

Hyland, L., Toma.szek, T, and Meek, T, 1991. Human immunodeficiency viru.s-1 protease 2 Use of pH rate. studies and solvent isotope effects to elucidate details of chemical mechanism. Biochemistry 30 8454-8463. 

Dediazoniation does not show a significant solvent isotope effect ( h2o/ d2o = 0.98 0.01 Crossley et al., 1940 Swain et al., 1975 a). This result is definitely not consistent with a mechanism in which charge is built up on oxygen in the rate-limiting transition state, as expected for an ANDN-like process. 

Hartshorn and Ridd48 showed that there is a negligible solvent isotope effect on nitrating anilinium ions in sulphuric acid and deuterated sulphuric acid (cf. an earlier less accurate determination by Brickman and Ridd48). The absence of a solvent isotope effect also argues against reaction on the free base because the free base concentration would be lower by a factor of about four in the deuterium-containing medium. Consequently, the differences in the rate coefficients in Table 6... 

The log rate versus acid strength curve for the latter compound is of the exact form expected for reactions of the free base, whilst that of the former compound is intermediate between this form and that obtained for the nitration of aniline and phenyltrimethylammonium ion, i.e. compounds which react as positive species. That these compounds react mainly or entirely via the free base is also indicated by the comparison of the rate coefficients in Table 8 with those in Table 5, from which it can be seen that the nitro substituent here only deactivates weakly, whilst the chloro substitutent appears to activate. In addition, both compounds show a solvent isotope effect (Table 9), the rate coefficients being lower for the deuterium-containing media, as expected since the free base concentration will be lower in these. 

VARIATION OF SOLVENT ISOTOPE EFFECT WITH MEDIUM COMPOSITION IN REACTION... 

Further substrate and solvent isotope effects were measured by Batts and Gold472 for the dedeuteration and detritiation of labelled 1,3,5-trimethoxy-benzene in aqueous protium- and deuterium-containing perchloric acid. Contrary to the observations above, they found the rate coefficients for dedeuteration to detritiation to be independent of the concentration of the catalysing acid (Table 125). Detritiation in the deuterium-containing aqueous perchloric acid media occurred 1.68 times faster than in the protium-containing media. 

Thus the above observations indicate that the reaction mechanism is not A-l and confirmation was provided by measurement of the solvent isotope effect kH/kD for protodeboronation of 4-methoxybenzeneboronic acid in 6.3 M sulphuric... 

SOLVENT ISOTOPE EFFECTS FOR REACTION OF ARYLBORONIC ACIDS WITH ACID IN... 

Measurements of the solvent isotope effect for different aromatic substrates in a range of sulphuric acid media (Table 196) showed the values to increase as... 

A further examination of the solvent isotope effect in 65-100 mole % H20-CF3C00H or D20-CF3C00D at 25 °C showed a maximum in the rate with both media at ca. 85 mole % acid (Table 228), as was also observed for... 

RATE COEFFICIENTS AND SOLVENT ISOTOPE EFFECT FOR REACTION OF 4-ClC6H4SiMe3 WITH AQUEOUS TRIFLUOROACETIC ACID AT 25 "C471... 

This prediction has now been confirmed by the observation (R. Alexander, C. Eaborn and T. G. Traylor, /. Organometal. Chem., 21 (1970) P65) that a solvent-isotope effect is obtained in base cleavage of benzyl- and aryl-tin bonds by NaOH in MeOH-MeOD. 

If one limits the consideration to only that limited number of reactions which clearly belong to the category of nucleophilic aromatic substitutions presently under discussion, only a few experimental observations are pertinent. Bunnett and Bernasconi30 and Hart and Bourns40 have studied the deuterium solvent isotope effect and its dependence on hydroxide ion concentration for the reaction of 2,4-dinitrophenyl phenyl ether with piperidine in dioxan-water. In both studies it was found that the solvent isotope effect decreased with increasing concentration of hydroxide ion, and Hart and Bourns were able to estimate that fc 1/ for conversion of intermediate to product was approximately 1.8. Also, Pietra and Vitali41 have reported that in the reaction of piperidine with cyclohexyl 2,4-dinitrophenyl ether in benzene, the reaction becomes 1.5 times slower on substitution of the N-deuteriated amine at the highest amine concentration studied. 

In this, as in many catalysed reactions, the protonated substrate is postulated as an intermediate, and although the proposed reaction scheme in fact accords with all the known experimental facts it perhaps would be instructive to determine the dependence of the rate coefficient on the Hammett acidity function at high acid concentration and also to investigate the solvent isotope effect kD2JkH20. Both these criteria have been used successfully (see Sections 2.2-2.4) to confirm the intermediacy of the protonated substrate in other acid-catalysed aromatic rearrangements. 

Secondly, it has been found that the benzidine rearrangement is subject to a solvent isotope effect d2o/ h2o > 1- If a proton is transferred from the solvent to the substrate in a rate-determining step the substitution of protium by deuterium will lead to a retardation in the rate of reaction (primary isotope effect) whereas if a proton is transferred in a fast equilibrium step preceeding the rate-determining step as in... 

The kinetic data based on the demonstration of specific acid catalysis in buffers, solvent isotope effects and acidity functions all support mechanisms where the proton-transfers are fast. It is possible to write equations which accommodate these facts together with the first-order dependence on hydrazo-compound and the concurrent first and second-order dependence on acidity. These are... 

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