Primary isotope effects temperature dependence

Finally the temperature dependence of the primary isotope effects was determined. Here the traditional expectations of Chart 3 were fully met the results translate into A /Ad = 1.1 0.1, = 0.8 kcaFmol. Thus the amount of... 

Magnesium bis(hexamethyldisilazide), Mg(HMDS)2, catalyses the enolization of ketones.287 On addition to propiophenone in toluene at ambient temperature, a ca 3 1 E Z mixture of enolates (103, R=SiMe3) is formed. These enolates, and an initial ketone complex, have been characterized by NMR, X-ray, IR, and UV-visible spectroscopy and computational studies. Kinetics of tautomerization have been measured, with proton transfer confirmed as rate determining ( hAd = 18.9 at 295 K). The significant temperature dependence of the primary isotope effect is indicative of tunnelling. 

Finally the temperature dependence of the primary isotope effects was determined. Here the traditional expectations of Chart 3 were fully met the results translate into AH/AD = 1.1 0.1, aD — aH = 0.8 kcal/mol. Thus the amount of tunneling present, adequate to produce the observed exaltation of secondary isotope effects, violations of the Swain-Schaad relationship, and violations of the Rule of the Geometric Mean in the neighborhood of room temperature, does not lead to anomalies in either the ratio of isotopic pre-exponential factors nor the isotopic activation energy difference over the temperature range studied (approximately 0-40 °C). As will be seen later, the temperature dependence of isotope effects for reactions that include tunneling is in general a complex, unresolved issue. 

Just how large the rate difference is depends on the nature of the TSs. The maximum effect occurs when the hydrogen being transferred is bound about equally to two other atoms at the TS. The calculated maximum for the isotope effect h/ d involving C—H bonds is about 7 at room temperature. When bond breaking is more or less than half complete at the TS, the isotope effect is smaller and can be close to 1 if the TS is very reactant-like or very product-like. Primary isotope effects can provide two very useful pieces of information about a reaction mechanism. First, the existence of a substantial isotope effect, i.e., > 2, is strong evidence that the... 

Equilibrium constants determined at 13-36°C by IR measurements of Vco show that the thermochemical parameters for binding of H2 are AH° = — 6.8 0.5 kcal/mol and AS° = —24.7 2.0 e.u. (these newer values are more accurate than those in Table 7.5). For binding of D2, AH° = -8.6 0.5 kcal/mol and AS° = -30.0 2.0 e.u., i.e., D2 binds better enthalpically (AAH = 1.8 kcal/mol), which easily overcomes the disfavored entropy of D2 complexation (AA5 = 5.3 cal/mol deg). This domination of enthalpy over entropy is general to these primary isotope effects (unlike, e.g.,H2 versus N2 binding), and thus EIEs are enthalpically driven. It should be kept in mind that EIEs are temperature-dependent because of the entropy differences. 

Part of the isotope effect is temperature dependent, but for the primary isotope effect the reaction coordinate motion effect, which is always normal, is temperature independent. The primary isotope effects are almost always normal. Secondary isotope effects can be either normal or inverse. 

Primary isotope effects can, of course, be also useful. The chemical shift difference between the OH and the SH protons is in this case very large (16 — 5 = 11 ppm) [18], depending slightly on the nature of R. The shift will be in the direction of A. This will lead to a negative contribution to the primary isotope effect. Experimentally, it is seen that both positive and negative primary isotope effects are found depending on temperature, solvent, and, with that, the position of the equihbrium. In Andresen... 

San Filippo and coworkers163 have determined the temperature dependence of the primary hydrogen-deuterium kinetic isotope effects for the hydrogen transfer reactions between several organic radicals and tributyltin hydride (deuteride) see equation 116. 

Not only primary but also secondary hydrogen isotope effects can be indicative of tunneling. The most frequently employed criteria of tunneling are the temperature dependence of kinetic isotope effects and the isotopic ratio of the pre-exponential factors in Arrhenius plots, but the pre-exponential criterion has been shown to be invalid for small secondary isotope effects. 

Fig. 1 Lewis and Funderburk found that the H/D primary kinetic isotope effects (25 °C in aqueous t-butyl alcohol) for proton abstraction from 2-nitropropane by pyridine derivatives all exceed the maximum isotope effect that could have been derived from the isotopic difference in reactant-state zero-point energies alone (a value around 7). The magnitude of the isotope effect increases with the degree of steric hindrance to reaction presented by the pyridine derivative, the identical results for 2,6-lutidine and 2,4,6-collidine ruling out any role for electronic effects of the substituents. The temperature dependence shown for 2,4,6-collidine is exceedingly anomalous the pre-exponential factor Ahis expected to be near unity but is instead about 1/7, while the value of AH — AH = 3030 cal/mol would have generated an isotope effect at 25 °C of 165 if the pre-exponential factor had indeed been unity.

These studies had therefore found the tunneling phenomenon, with coupled motion, as the explanation for failures of these systems to conform to the expectations that the kinetic secondary isotope effects would be bounded by unity and the equilibrium effect and that the primary and secondary effects would obey the Rule of the Geometric Mean (Chart 3), as well as being consistent with the unusual temperature dependences for isotope effects that were predicted by Bell for cases involving tunneling. 

Lewis et al. (entry 11 of Table 2) examined the temperature-dependence of isotope effects in the action of both the human enzyme and the soybean enzyme, by measuring the relative amounts of per-protio and per-deuterio-13-hydroperoxy-products by HLPC. The observed effects are, therefore, composed of primary, secondary, and perhaps remote isotope-effect contributions. Isotope effects on fecat/ M for both enzymes (determined by competition between labeled substrates) are increased by high total substrate concentration, an effect previously observed but stiU ill-understood. At 100 /rM substrate, the effects are roughly independent of temperature below about 15 °C, and are about 60 (H/D) for the human enzyme and 100 (H/D) for the soybean enzyme. Above 15 °C, the effects decline to about 50 for the human enzyme and about 60 for the soybean enzyme, perhaps because non-isotope-sensitive steps become more nearly rate-limiting (see Chart 4). 

This study on the kinetic chlorine isotope effect in ethyl chloride50 was extended to secondary and tertiary alkyl halides pyrolyses51. The isotope effects on isopropyl chloride and terf-butyl chloride pyrolysis were found to be primary and exhibited a definite dependence on temperature. They increased with increasing methyl substitution on the central carbon atom. The pyrolysis results and model calculations implied that all alkyl chlorides involve the same type of activated complex. The C—Cl bond is not completely broken in the activated complex, yet the chlorine participation involves a combination of bending and stretching modes. 

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