Kinetic isotope effects structures

A substantial body of data, including reaction kinetics, isotope effects, and structure-reactivity relationships, has permitted a thorough understanding of the steps in aromatic nitration. As anticipated from the general mechanism for electrophilic substitution, there are three distinct steps ... 

Consider a reactant molecule in which one atom is replaced by its isotope, for example, protium (H) by deuterium (D) or tritium (T), C by C, etc. The only change that has been made is in the mass of the nucleus, so that to a very good approximation the electronic structures of the two molecules are the same. This means that reaction will take place on the same potential energy surface for both molecules. Nevertheless, isotopic substitution can result in a rate change as a consequence of quantum effects. A rate change resulting from an isotopic substitution is called a kinetic isotope effect. Such effects can provide valuable insights into reaction mechanism. 

Despite its apparent simplicity, the PK pyrrole synthesis has retained its mystique since being discovered. Several investigations into the PK mechanism have been reported, including a gas phase study. Current evidence (intermediate isolation, kinetics, isotope effects) suggests the following (abbreviated) mechanism for the formation of pyrrole 13. However, the specific PK mechanism is often dependent on pH, solvent, and amine and dicarbonyl structure, especially with regard to the ringclosing step. 

What concerns us here are three topics addressing the fates of bromonium ions in solution and details of the mechanism for the addition reaction. In what follows, we will discuss the x-ray structure of the world s only known stable bromonium ion, that of adamantylideneadamantane, (Ad-Ad, 1) and show that it is capable of an extremely rapid degenerate transfer of Br+ in solution to an acceptor olefin. Second, we will discuss the use of secondary a-deuterium kinetic isotope effects (DKie) in mechanistic studies of the addition of Br2 to various deuterated cyclohexenes 2,2. Finally, we will explore the possibility of whether a bromonium ion, generated in solution from the solvolysis of traAU -2-bromo-l-[(trifluoromethanesulfonyl)oxy]cyclohexane 4, can be captured by Br on the Br+ of the bromonium ion, thereby generating olefin and Br2. This process would be... 

Mechanistic studies have been designed to determine if the concerted cyclic TS provides a good representation of the reaction. A systematic study of all the E- and Z-decene isomers with maleic anhydride showed that the stereochemistry of the reaction could be accounted for by a concerted cyclic mechanism.19 The reaction is only moderately sensitive to electronic effects or solvent polarity. The p value for reaction of diethyl oxomalonate with a series of 1-arylcyclopentenes is —1.2, which would indicate that there is little charge development in the TS.20 The reaction shows a primary kinetic isotope effect indicative of C—H bond breaking in the rate-determining step.21 There is good agreement between measured isotope effects and those calculated on the basis of TS structure.22 These observations are consistent with a concerted process. 

Today a good understanding of transition state structure can be obtained through a combination of experimental measurements of kinetic isotope effects (KIE) and computational chemistry methods (Schramm, 1998). The basis for the KIE approach is that incorporation of a heavy isotope, at a specific atom in a substrate molecule, will affect the enzymatic reaction rate to an extent that is correlated with the change in bond vibrational environment for that atom, in going from the ground state to the... 

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

The physical organic chemistry of very high-spin polyradicals, 40, 153 Thermodynamic stabilities of carbocations, 37, 57 Topochemical phenomena in solid-slate 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... 

Using kinetic isotope effects to determine the structure of the transition states of SN2 reactions, 41, 219... 

The crystal structure of an isopropylamine complex of Ru of this type has been reported [78]. Surprisingly, a negligible kinetic isotope effect (kRuHOH/kRUDOD= 1.05 0.14) was found when D labels on both the OH and RuH sites were used,... 

The present findings suggest that mechanistic and reaction product variations are not necessarily accompanied by a clear difference in reactivity and the TS structure, and hence experimentally observable quantities, such as relative reactivities (Hammett equation) and kinetic isotope effects (KIEs), which are commonly considered to be useful means to detect a change in reaction mechanism (77,72), may not always be useful. 

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. 

The presence of a significant kinetic isotope effect for the losses of OH from the nitroazoles (ThAd = 4.6) supports the suggestion that the fragmentations are adequately described by a stepwise hydrogen transfer, followed by cleavage of the OH moiety or, alternatively, rearrangement to structures which can eliminate OH and H2O98. 

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. 

---