Secondary Deuterium Kinetic Isotope Effects and Transition State

Deuterium kinetic isotope effects, secondary, and transition state structure, 31,143 Diazo compounds, aliphatic, reactions with acids, 5, 331... 

Tetrahedral intermediates, derived from carboxylic acids, spectroscopic detection and the investigation of their properties, 21, 37 Thermodynamic stabilities of carbocations, 37, 57 Topochemical phenomena in solid-state chemistry, 15, 63 Transition state analysis using multiple kinetic isotope effects, 37, 239 Transition state structure, crystallographic approaches to, 29, 87 Transition state structure, in solution, effective charge and, 27, 1 Transition state structure, secondary deuterium isotope effects and, 31, 143 Transition states, structure in solution, cross-interaction constants and, 27, 57 Transition states, the stabilization of by cyclodextrins and other catalysts, 29, 1... 

Transition state analysis using multiple kinetic isotope effects, 37, 239 Transition state structure, crystallographic approaches to, 29, 87 Transition state structure, in solution, effective charge and, 27, 1 Transition stale structure, secondary deuterium isotope effects and,... 

The density functional theory calculations of primary 14C KIE and secondary deuterium kinetic isotope effects (SKIE)220 did not reproduce satisfactorily all the experimentally determined 14C KIE and deuterium (4,4-2H2)- and 6,6-2H2-SKIE, though the non-local DFT methods provide transition state energies on a par with correlated molecular orbital theory221. 

Secondary Deuterium Kinetic Isotope Effects and Transition State Structure... 

Secondary a-deuterium kinetic isotope effects (KIEs) have been widely used to determine the mechanism of SN reactions and to elucidate the structure of their transition states (Shiner, 1970a Westaway, 1987a). Some of the significant studies illustrating these principles are presented in this section. 

A secondary deuterium kinetic isotope effect is observed when substitution of a deuterium atom(s) for a hydrogen atom(s) in the substrate changes the rate constant but the bond to the deuterium atom is neither broken nor formed in the transition state of the rate-determining step of the reaction. Several types of secondary hydrogen-deuterium (deuterium) KIEs are found. They are characterized by the position of the deuterium relative to the reaction centre. Thus, a secondary a-deuterium KIE is observed when an a-hydrogen(s) is replaced by deuterium [equations (1) and (2)], where L is either hydrogen or deuterium. 

Several monographs2-5 have detailed discussions dealing with heavy-atom and primary and secondary hydrogen-deuterium kinetic isotope effects. The monograph by Melander and Saunders5 covers the entire area particularly well. For this reason, only a brief summary of the theory of kinetic isotope effects as well as their important uses in the determination of reaction mechanism and transition-state geometry will be presented. 

Other workers have concluded that the transition state for the Menshutkin reaction is late with more nitrogen-alpha carbon bond formation than alpha carbon-leaving group bond rupture. For instance, Harris and coworkers51 found that the secondary alpha deuterium kinetic isotope effects (Table 8) decreased when a poorer nucleophile was used in the S v 2 reactions between 3,5-disubstituted pyridines and methyl iodide in 2-nitropropane at 25 °C (equation 38, Table 8). 

Finally, it is worth noting that the substituent effects are different on the two types of Menshutkin reactions as well. For the benzyl substrates, changing to a better nucleophile, i.e. changing the substituent on the nucleophile from the meta-nitro to a para-methoxy substituent, leads to a later, more product-like transition state with more inverse secondary incoming nucleophile deuterium kinetic isotope effects. Flowever, the same change in nucleophile in the reactions with the methyl and ethyl substrates leads to an earlier transition state and less inverse secondary incoming nucleophile deuterium kinetic isotope effects. 

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