Kinetic isotope effects origin

When one of the ortho hydrogens is replaced by deuterium, the rate drops from 1.53 X 10 " s to 1.38 X lO s. What is the kinetic isotope effect The product from such a reaction contains 60% of the original deuterium. Give a mechanism for this reaction that is consistent with both the kinetic isotope effect and the deuterium retention data. 

Support for such an interaction of the H—C bonds with the carbon atom carrying the positive charge is provided by substituting H by D in the original halide, the rate of formation of the ion pair is then found to be slowed down by 10% per deuterium atom incorporated a result compatible only with the H—C bonds being involved in the ionisation. This is known as a secondary kinetic isotope effect, secondary... 

Isotope Effects in C-H Bond Activation Reactions by Transition Metals (225) were reviewed, and some pitfalls in interpreting kinetic isotope were pointed out. The interpretation of the kinetic isotope effects offered by the authors of the original reports (75,76,85) on the system shown in Schemes 15,16 was criticized. 

The electrophile E+ attacks the unhindered side of the still unsubstituted second aromatic ring. A proton (deuteron) is transferred from this ring to the second, originally substituted ring, from which it leaves the molecule. Thus, the electrophile enters, and the proton (deuteron) leaves the [2.2]paracyclophane system by the least hindered paths. Some migration of deuterium could be detected in the bromination of 4-methyl[2.2]paracyclophane (79). The proposed mechanism is supported by the kinetic isotope effects ( h/ d) found for bromination of p-protio and p-deuterio-4-methyl[2.2]paracyclophanes in various solvents these isotope effects demonstrate that proton loss from the a complex is the slowest step. 

The simplest version of the origin of kinetic isotope effects holds that, say A h/A d will given by ... 

Fig. 2.16. Origin of kinetic isotope effects. [4,5,66] The change in vibrational frequencies, and thus in density of states causes somewhat higher activation energy and consequently smaller excess energy for the reaction of the deuterated bond, and thus reduces kxj.

The kinetic isotope effect has its origin in force constant changes occurring at an isotopically substituted position as the react2mt is converted into an activated complex. Hence it provides information about the transition state in the solvolysis reaction, but not necessarily about the stmcture of possible intermediates. This limits the utility of information drawn from isotope studies in resolving the structure of ions under stabilizing conditions. 

Nearly all kinetic isotope effects (KIE) have their origin in the difference of isotopic mass due to the explicit occurrence of nuclear mass in the Schrodinger equation. In the nonrelativistic Bom-Oppenheimer approximation, isotopic substitution affects only the nuclear part of the Hamiltonian and causes shifts in the rotational, vibrational, and translational eigenvalues and eigenfunctions. In general, reasonable predictions of the effects of these shifts on various kinetic processes can be made from fairly elementary considerations using simple dynamical models. 

Repeated deprotonation of 278 removed due to a high H/D kinetic isotope effect the 1-proton, forming the dideuterio compound 279 with low diastereoselectivity . It is quite likely that a dynamic thermodynamic resolution is the origin. Intermediate 277 is configurationally labile, enabling an equilibration of the diastereomeric ion pairs 277 and epi-211. Similar studies were undertaken with 1-phenyl-l-pyrid-2-ylethane (280) and l-(4-chlorophenyl)-l-(pyrid-2-yl)-3-(dimethylamino)propane (281) (50% eef. An improvement of the achieved enantiomeric excesses resulted when external chiral proton sources, such as 282 or 283, were applied (84% ee for 280 with 283 and 75% ee for 281). 

These results, as well as rate studies " and kinetic isotope effects ", support a concerted, 5ptra-structured oxenoid-type transition state for the CH oxidations". The original oxygen-rebound mechanism has been discounted (see the computational work in Section I.D). Recently, however, the stepwise radical mechanism was revived in terms of the so-called molecule-induced homolysis , but such radical-type reactivity was severely criticized on the basis of experimental" and theoretical grounds. 

We have examined the proton transfer reaction AH-B A -H+B in liquid methyl chloride, where the AH-B complex corresponds to phenol-amine. The intermolecular and the complex-solvent potentials have a Lennard-Jones and a Coulomb component as described in detail in the original papers. There have been other quantum studies of this system. Azzouz and Borgis performed two calculations one based on centroid theory and another on the Landau-Zener theory. The two methods gave similar results. Hammes-Schiffer and Tully used a mixed quantum-classical method and predicted a rate that is one order of magnitude larger and a kinetic isotope effect that is one order of magnitude smaller than the Azzouz-Borgis results. 

The original experimental evidence for concerted acid-base catalysis of the mutarotation in benzene is now considered unsound133 134 and concerted acid-base catalysis has been difficult to prove for nonenzy-matic reactions in aqueous solution. However, measurements of kinetic isotope effects seem to support Swain and Brown s interpretation.135 Concerted acid-base catalysis by acetic acid and acetate ions may have been observed for the enolization of acetone136 and it may be employed by enzymes.1363... 

The value of the kinetic isotope effect method lies mainly in the possibility of making a substitution within tlve reactive center of the molecule, while still retaining the original type of the read ion, thus allowing the cancellation of many poorly defined quantities in the absolute rate equations and permitting a direct comparison between the measured and calculated values of the relative rate constants. Since the magnitude of these latter values depends on the hypothetical transition state model, a diagnostic means is provided by the method for the experimental verification of the nature of tlie transition state in question. 

The origin of the kinetic isotope effect lies in the dependence of rate constants of transfer of isotopes with masses ml and m2 is temperature-independent and equal to... 

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