Editing Kinetic isotope effect (section)

=== Isotope effects with elements heavier than carbon ===
Interpretation of carbon isotope effects is usually complicated by simultaneously forming and breaking bonds to carbon. Even reactions that involve only bond cleavage from the carbon, such as S{{sub|N}}1 reactions, involve strengthening of the remaining bonds to carbon. In many such reactions, leaving group isotope effects tend to be easier to interpret. For example, substitution and elimination reactions in which [[chlorine]] acts as a leaving group are convenient to interpret, especially since chlorine acts as a monatomic species with no internal bonding to complicate the reaction coordinate, and it has two stable isotopes, {{sup|35}}Cl and {{sup|37}}Cl, both with high abundance. The major challenge to the interpretation of such isotope affects is the solvation of the leaving group.<ref name="Saunders" />

Owing to experimental uncertainties, measurement of isotope effect may entail significant uncertainty. Often isotope effects are determined through complementary studies on a series of isotopomers. Accordingly, it is quite useful to combine hydrogen isotope effects with heavy-atom isotope effects. For instance, determining nitrogen isotope effect along with hydrogen isotope effect was used to show that the reaction of 2-phenylethyltrimethylammonium ion with ethoxide in ethanol at 40°C follows an E2 mechanism, as opposed to alternative non-concerted mechanisms. This conclusion was reached upon showing that this reaction yields a nitrogen isotope effect, ''k''{{sub|14}}/''k''{{sub|15}}, of 1.0133±0.0002 along with a hydrogen KIE of 3.2 at the leaving hydrogen.<ref name="Saunders" />

Similarly, combining nitrogen and hydrogen isotope effects was used to show that syn eliminations of simple ammonium salts also follow a concerted mechanism, which was a question of debate before. In the following two reactions of 2-phenylcyclopentyltrimethylammonium ion with ethoxide, both of which yield 1-phenylcyclopentene, both isomers exhibited a nitrogen isotope effect ''k''{{sub|14}}/''k''{{sub|15}} at 60°C. Though the reaction of the trans isomer, which follows syn elimination, has a smaller nitrogen KIE (1.0064) than the cis isomer which undergoes anti elimination (1.0108); both results are large enough to be indicative of weakening of the C-N bond in the transition state that would occur in a concerted process.{{efn|In the diagrams below, "Et" means [[ethyl radical|ethyl]], C{{sub|2}}H{{sub|5}}; "Ph" means [[phenyl]], C{{sub|6}}H{{sub|5}}. Phenyl is also called by the symbol Φ ([[phi]]).}}
[[File:Elimination reactions of 2-phenylcyclopentyltrimethylammonium isomers.png|center]]