Alpha-secondary isotope effects

Kurz, L.C. and Erieden, C. (1980). Anomalous equilibrium and kinetic alpha-deuterium secondary isotope effects accompanying hydride transfer from reduced nicotinamide adenine dinucleotide. J. Am. Chem. Soc. 102, 4198-4203... 

Apart from a few studies (ref. 7), the use of deuterium kinetic isotope effects (kie s) appears to have had limited use in mechanistic studies of electrophilic bromination of olefins. Secondary alpha D-kie s have been reported for two cases, trans-stilbene fi and p-substituted a-d-styrenes 2, these giving relatively small inverse kie s of... 

The primary hydrogen-deuterium kinetic isotope effect for the reaction was 3.7 and the secondary alpha-deuterium kinetic isotope effect was found to be 1.1. It is worth noting that the primary hydrogen-deuterium kinetic isotope effect of 3.7 is in excellent agreement... 

C. Secondary Alpha Hydrogen-Deuterium Kinetic Isotope Effects. 896... 

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). 

TABLE 8. The secondary alpha hydrogen-deuterium kinetic isotope effects for the Menshutkin reaction between 3,5-disubstituted pyridines and methyl iodide in 2-nitropropane at 25 °C... 

TABLE 9. The carbon-12/carbon-14 and secondary alpha hydrogen-tritium kinetic isotope effects for the Sat2 reactions between Y-substituted /VA-dimethylanilines and Z-substituted benzyl X-substituted benzensulfonates in acetone at 35°C ... 

TABLE 10. The secondary alpha deuterium and secondary incoming nucleophile deuterium kinetic isotope effects found for the S 2 reactions between para-substituted anilines and benzylamines with benzyl, methyl and ethyl para-substituted benzensulfonates in ace- ... 

TABLE 13. The secondary alpha hydrogen-deuterium and primary nitrogen kinetic isotope effects for the SN2 reaction between sodium thiophenoxide and benzyldimethylphenylammonium nitrate at different ionic strengths in DMF at 0 C... 

The nucleophile in the S.v2 reactions between benzyldimethylphenylammonium nitrate and sodium para-substituted thiophenoxides in methanol at 20 °C (equation 42) can exist as a free thiophenoxide ion or as a solvent-separated ion-pair complex (equation 43)62,63. The secondary alpha deuterium and primary leaving group nitrogen kinetic isotope effects for these Sjv2 reactions were determined to learn how a substituent on the nucleophile affects the structure of the S.v2 transition state for the free ion and ion-pair reactions64. 

TABLE 14. The secondary alpha deuterium kinetic isotope effects and primary leaving group nitrogen kinetic isotope effects for the free ion and ion-pair S 2 reactions between benzyldimethylphenylammonium nitrate and para-substituted thiophenoxide ions in methanol at 20 °C... 

Unfortunately, the isotope effects were measured at different temperatures. Applying an average temperature dependence of 0.008 per 20 °C to the secondary alpha deuterium... 

Secondary hydrogen kinetic isotope effects are further classified as alpha, beta, etc. depending on the distance of the isotopically substituted atom from the bond(s) that is (are) being made or broken (a = 1 bond, 3 = 2 bonds, etc.). Consider the simple Sn2 reaction between hypochlorite anion and ethyl chloride ... 

Welsh, K.M., Creighton, D.J. and Khnman, J.P. (1980). Transition-state structure in the yeast alcohol dehydrogenase reaction the magnitude of solvent and alpha-secondary hydrogen isotope effects. Biochemistry 19, 2005-2016... 

Karsten, W.E., Hwang, C.C. and Cook, P.F. (1999). Alpha-secondary tritium kinetic isotope effects indicate hydrogen tunneling and coupled motion occur in the oxidation of L-malate by NAD-malic enzyme. Biochemistry 38, 4398-4402... 

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