Kinetic isotope effects determination

The intramolecular kinetic isotope effect determined in reaction of BTNO with p-MeO-C6H4CH(D)0H gave a h/ d ratio of 5.6 in MeCN , consistent with a rate-determining H-abstraction step. Additional determinations gave a h/ d of 7 with PhCH(D)OH, and 12 for the intermolecular competition of fluorene vs. 9,9-dideuteriofluorene. The latter value supports the contribution of tunnelling already commented on for reaction of PINO with various C—H donors ( h/ d values in the 11-27 range) . ... 

A complete set of 13C kinetic isotope effects determined (by a natural abundance CMR method) for addition of lithium dibutylcuprate to cyclohexenone, in THF at —78°C, have been shown to be consistent with those calculated theoretically for ratedetermining reductive elimination from an intermediate square-planar copper complex.120 Thus, die KIE (12k/13k) = 1.020-1.026 at C(3) is indicative of substantial bonding change, and partial alkyl transfer can explain the significant low KIE = 1.011-1.016 for Ca of die butyl group. 

C-2 was observed in the residual alanine, it can be inferred that once the carhanion is formed, it reacts readily with the thioester. The deuterium kinetic isotope effect determined with [ H]Ala was weak 1.3),... 

The efficiency of oxidation of open-chain alkyl, cycloalkyl, and unsaturated alcohols in acetonitrile by 9-phenylxanthylium ion (PhXn+) was dependent on the alcohol stmc-tures. Structure-reactivity relationship was discussed with relation to formation of a carbocationic transition state (C +-OH). Kinetic isotope effects determined at a-D, p-D3, and OD positions for the reaction of 1-phenylethanol suggested a hydride-proton sequential transfer mechanism that involved a rate-limiting formation of the a-hydroxy carbocation intermediate. Unhindered secondary alkyl alcohols were selectively oxidized in the presence of primary and hindered secondary alkyl alcohols. Strained C(7)-C(ll) cycloalkyl alcohols reacted faster than cyclohexyl alcohol, whereas the strained C(5) and C(12) alcohols reacted slower. Aromatic alcohols were oxidized efficiently and selectively in the presence of aliphatic alcohols of comparable steric requirements. ... 

Melander first sought for a kinetic isotope effect in aromatic nitration he nitrated tritiobenzene, and several other compounds, in mixed acid and found the tritium to be replaced at the same rate as protium (table 6.1). Whilst the result shows only that the hydrogen is not appreciably loosened in the transition state of the rate-determining step, it is most easily understood in terms of the S 2 mechanism with... 

A special type of substituent effect which has proved veiy valuable in the study of reaction mechanisms is the replacement of an atom by one of its isotopes. Isotopic substitution most often involves replacing protium by deuterium (or tritium) but is applicable to nuclei other than hydrogen. The quantitative differences are largest, however, for hydrogen, because its isotopes have the largest relative mass differences. Isotopic substitution usually has no effect on the qualitative chemical reactivity of the substrate, but often has an easily measured effect on the rate at which reaction occurs. Let us consider how this modification of the rate arises. Initially, the discussion will concern primary kinetic isotope effects, those in which a bond to the isotopically substituted atom is broken in the rate-determining step. We will use C—H bonds as the specific topic of discussion, but the same concepts apply for other elements. 

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. 

A number of studies of the acid-catalyzed mechanism of enolization have been done. The case of cyclohexanone is illustrative. The reaction is catalyzed by various carboxylic acids and substituted ammonium ions. The effectiveness of these proton donors as catalysts correlates with their pK values. When plotted according to the Bronsted catalysis law (Section 4.8), the value of the slope a is 0.74. When deuterium or tritium is introduced in the a position, there is a marked decrease in the rate of acid-catalyzed enolization h/ d 5. This kinetic isotope effect indicates that the C—H bond cleavage is part of the rate-determining step. The generally accepted mechanism for acid-catalyzed enolization pictures the rate-determining step as deprotonation of the protonated ketone ... 

A distinction between these four possibilities can be made on the basis of the kinetic isotope effect. There is no isotope effect in the arylation of deuterated or tritiated benzenoid compounds with dibenzoyl peroxide, thereby ruling out mechanisms in which a C5— bond is broken in the rate-determining step of the substitution. Paths (ii) and (iii,b) are therefore eliminated. In path (i) the first reaction, Eq. (6), is almost certain to be rate-determining, for the union of tw o radicals, Eq. (7), is a process of very low activation energy, while the abstraction in which a C—H bond is broken would require activation. More significant evidence against this path is that dimers, Arz, should result from it, yet they are never isolated. For instance, no 4,4 -dinitrobiphenyl is formed during the phenylation of... 

Grovenstein and Kilby218 showed that the kinetic isotope effect kH/kD is 3.97 for the iodination 2,4,6-trideuterophenol by iodine in aqueous buffer at 25 °C, and this is in accord with the base catalysis described above. However, this large isotope effect means that the intermediate is in fairly rapid equilibrium with the reactants, so that it is difficult to determine from kinetic studies which iodinating species is involved. Thus it might be positive iodine, equilibria (112), (113), (115)... 

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... 

Leffek, Llewellyn and Robertson (1960a, b) made careful conductometric determinations of deuterium kinetic isotope effects on the solvolysis rates (in water) of some ethyl, isopropyl and n-propyl sulphonates and halides. In the case of the n-propyl compoimds,... 

Brown and McDonald (1966) provided another type of kinetic evidence for these size relationships by determining secondary kinetic isotope effects in reactions of pyridine-4-pyridines with alkyl iodides. For example, the isotopic rate ratio in the reaction between 4-(methyl-d3)-pyridine and methyl iodide at 25-0 C in nitrobenzene solution was determined to be kjyfk = l-OOl, while that in the corresponding reaction with 2,6-(dimethyl-d6)-pyridine was 1-095. (Brown and McDonald (1966) estimate an uncertainty of 1% in the k jk values.) Furthermore, the isotopic rate ratio in the case of the 2-(methyl-d3)-compound increased from 1 030 to 1-073 as the alkyl group in the alkyl iodide was changed from methyl to isopropyl, i.e. the isotope effect increased with increasing steric requirements of the alkyl iodide. 

Kaplan and Thornton (1967) determined secondary kinetic isotope effects in two 8 2 displacement reactions, one of which involved quatemi-zation of N,N-dimethylaniline and N,N-dimethyl-eig-aniline with methyl p-toluenesulphonate (CHgOTs). The reactions were carried out in... 

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