Secondary Kinetic Isotope Effects in Substitution Mechanisms

Secondary Kinetic Isotope Effects in Substitution Mechanisms 

Shiner, Jr., Isotope Effects in Chemical Reactions, C. J. Collins and W. S. Bowman (eds.). Van Nostrand Reinhold Company, New York, 1970, Chap. 2. 

SECTION 5.9. SECONDARY KINETIC ISOTOPE EFFECTS IN SUBSTITUTION MECHANISMS 

The utility of kinetic isotope effects in probing reaction mechanisms was described in the preceding chapter, where it was pointed out that measurable secondary kinetic isotope effects were evident in reactions that do not involve cleavage of the bond to the isotopic nucleus. Measurements of secondary kinetic 

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Reactions of (ii)-l-decenyl(phenyl)iodonium salt (6a) with halide ions have been examined under various conditions. The products are those of substitution and elimination, usually (Z)-l-halodec-l-ene (6b) and dec-l-yne (6c), as well as iodobenzene (6d), but F gives exclusively elimination. In kinetic studies of secondary kinetic isotope effects, leaving-group substituent effects, and pressure effects on the rate, the results are compatible with the in-plane vinylic mechanism for substitution with inversion. The reactions of four ( )-jS-alkylvinyl(phenyl)iodonium salts with CP in MeCN and other solvents at 25 °C have been examined. Substitution with inversion is usually in competition with elimination to form the alk-l-yne. 

Investigation on secondary kinetic isotope effects with deuterium labeling on the arene suggests a reaction mechanism in which the C-H bond cleavage is the rate-determining step. This may explain the requirement for the methyl-substituted alkene in order to arrive at a more stabilized neopentyl-like palladium intermediate M. For 2-chlorophenyl as aryl substituent, the superiority of the present pathway was demonstrated over a potential sequence of oxidative insertion,... 

The kinetics and mechanism of the aminolysis of phenyl-substituted phenyl phosphonyl chlorides (136) with anilines (135) were investigated in MeCN at 55.0 °C. Very sensitive variation of /Oy(5/Oy2>0) with the change of substituent on the nucleophile Sax) led to a large negative cross-interaction constant, pxY = Spy)/ Sox) = —1.31. The secondary kinetic isotope effects observed with deuteriated aniline nucleophiles were of the inverse type (/th/ d = 0.61-0.87), and small A// (1.6-9.7kcalmor ) and large negative A5 (—43 to —65 e.u.) values were... 

Indicate mechanisms that would account for the formation of each product. Show how the isotopic substitution could cause a change in product composition. Does your mechanism predict that the isotopic substitution would give rise to a primary or secondary deuterium kinetic isotope effect Calculate the magnitude of the kinetic isotope effect from the data given. 

The kinetic isotope effect (KIE) results in variation of the reaction rate constant as a function of isotopic variations in either of the reactants. A primary isotope effect occurs when the labeled bond is directly involved in the reaction coordinate and a secondary isotope effect occurs when the labeled bond is elsewhere in the ion or molecule. The effect is greater for larger changes in relative isotope mass. Often, a precise measure of the KIE can provide valuable information regarding the reaction mechanism. The predominant cause of the KIE is variation in the zero-point vibration energy (ZPE) as a function of isotope mass since changes to the ZPE may alter the reaction enthalpy of activation. Isotope substitution also effects changes in the translation, rotation and vibration partition functions, which in turn alters the reaction entropy of activation. 

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