Carbon-13 isotope effects

Keywords NMR spectroscopy isotope effects carbon 13C deuterium natural abundance theoretical calculations reaction mechanisms... 

The occurrence of a hydrogen isotope effect in an electrophilic substitution will certainly render nugatory any attempt to relate the reactivity of the electrophile with the effects of substituents. Such a situation occurs in mercuration in which the large isotope effect = 6) has been attributed to the weakness of the carbon-mercury bond relative to the carbon-hydrogen bond. The following scheme has been formulated for the reaction, and the occurrence of the isotope effect indicates that the magnitudes of A j and are comparable ... 

Figure 1.9. NMR spectra of a mixture of ethanol and hexadeuterioethanol [27 75 v/v, 25 °C, 20 MHz], (a) H broadband decoupled (b) without decoupling. The deuterium isotope effect Sch - d on chemical shifts is 1.1 and 0.85 ppm for methyl and methylene carbon nuclei, respectively...

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). 

A second piece of evidence in support of the E2 mechanism is provided by a phenomenon known as the deuterium isotope effect. For reasons that we won t go into, a carbon-hydrogen bond is weaker by about 5 kj/mol (1.2 kcal/mol) than the corresponding carbon-rfaiiferiwm bond. Thus, a C-H bond is more easily broken than an equivalent C-D bond, and the rate of C-H bond cleavage is faster. For instance, the base-induced elimination of HBv from l-bromo-2-phenylethane proceeds 7.11 times as fast as the corresponding... 

In the El reaction, C-X bond-breaking occurs first. The substrate dissociates to yield a carbocation in the slow rate-limiting step before losing H+ from an adjacent carbon in a second step. The reaction shows first-order kinetics and no deuterium isotope effect and occurs when a tertiary substrate reacts in polar, nonbasic solution. 

A small isotope effect has been observed in nitration of benzene by nitronium borofluoride in tetramethylene sulphone at 30 °C (kH/kD = 0.86) and this has been attributed to a secondary effect of the change in hybridisation from sp2 to sp3 of the ring carbon during the course of the reaction109. However, naphthalene gives an isotope effect of 1.15 under the same conditions, and anthracene a value of 2.6115. It does not seem at all clear why these relatively unhindered and normally more reactive molecules should give rise to an isotope effect when benzene does not. 

Further evidence regarding the mechanism was provided by LynnandBoums643 , who found a pH-dependent carbon-13 isotope effect in the decarboxylation of 2,4-dihydroxybenzoic acid in acetate buffers. The dependence was interpreted in favour of the A-SE2 mechanism, for an increase in acetate concentration would increase kL t and hence partitioning of the intermediate so that k 2 becomes more rate-determining. 

Kinetic isotope effect. Calculate the kie for R-H/R-T and R-D/R-T, taking for a carbon-hydrogen bond a stretching frequency of 2900 cm 1. 

However, a number of examples have been found where addition of bromine is not stereospecifically anti. For example, the addition of Bf2 to cis- and trans-l-phenylpropenes in CCI4 was nonstereospecific." Furthermore, the stereospecificity of bromine addition to stilbene depends on the dielectric constant of the solvent. In solvents of low dielectric constant, the addition was 90-100% anti, but with an increase in dielectric constant, the reaction became less stereospecific, until, at a dielectric constant of 35, the addition was completely nonstereospecific.Likewise in the case of triple bonds, stereoselective anti addition was found in bromination of 3-hexyne, but both cis and trans products were obtained in bromination of phenylacetylene. These results indicate that a bromonium ion is not formed where the open cation can be stabilized in other ways (e.g., addition of Br+ to 1 -phenylpropene gives the ion PhC HCHBrCH3, which is a relatively stable benzylic cation) and that there is probably a spectrum of mechanisms between complete bromonium ion (2, no rotation) formation and completely open-cation (1, free rotation) formation, with partially bridged bromonium ions (3, restricted rotation) in between. We have previously seen cases (e.g., p. 415) where cations require more stabilization from outside sources as they become intrinsically less stable themselves. Further evidence for the open cation mechanism where aryl stabilization is present was reported in an isotope effect study of addition of Br2 to ArCH=CHCHAr (Ar = p-nitrophenyl, Ar = p-tolyl). The C isotope effect for one of the double bond carbons (the one closer to the NO2 group) was considerably larger than for the other one. ... 

---