Rate-determining intermediate transition state

TDI and TDTS are new terms that only have sense in catalysis. In noncatalytic reactions, it is more accurate to speak about rate-determining intermediate (RDI) and rate-determining intermediate transition state (RDTS) (or collectively, RDStates) [37, 54, 55]. However, the concept is not new (as always), and has been called by other names. The determining intermediate is also known as the resting state or the most abundant reaction intermediate MARI) [2, 22-24, 56]. Unfortunately, the kinetic importance of the TDI has been disregarded, rarely... 

Another possibility is that breakdown of the tetrahedral intermediate is rate determining, the transition state being very early, as in 2. 

AG, Free Energy of Activation Rate Constant Upper Limit on Concentration Diffusion-Controlled Limit Dropping the AG by 1.36 kcal/mol (5.73 kJ/mol) Increases the Rate of Reaction Tenfold at Room Temperature Reasonable Rate at 25°C Half-Life Lifetime of an intermediate Rate-Determining Step Transition State Position Reactivity vs. Selectivity Thermodynamic vs. Kinetic AG = AH -TAS, Enthalpy of Transition Entropy of Transition Stabilization of Intermediates Stabilization of Reactants... 

Figure 10.18 Catalytic monoclonal antibody (MAb) mediated ester hydrolysis. The MAb was generated through immunoreaction with the illustrated hapten linked to an appropriate carrier protein. The part of the hapten related to the substrate structure is shown in red. The phosphonate link is used as a transition state analogue of the rate determining step transition state leading to the key tetrahedral intermediate of ester hydrolysis. The MAb should optimally bind the rate determining step transition state relative to substrate or products in order to effect maximum catalytic effect.

This dramatic difference of behavior has been interpreted in terms of transition state 81). The benzene series has not enough electron-deficient character to determine a transition state similar to a charge-transfer complex, so that the reaction rates would be affected more by the stability of the intermediate cyclo-hexadienyl radicals (23, 24) than by polar effects... 

The models of these surface reactions (more details are given in Section 6.7) imply a number of assumptions (I) there is equilibrium in adsorption and desorption (2) there is only one rate-determining intermediate reaction between adsorbed species (3) the species on the surface are well mixed and (4) there is a thermal probability of a transition of the physisorbed to the chemisorbed state before subsequent reaction and diffusion. These assumptions are not independently proved but are justified by the degree of success of the models in predicting the kinetics. 

Since the early transition state does not involve covalent interaction with the nucleophile, the rate-determining intermediate also does not involve covalent interaction with the nucleophile, and is best represented as an ion pair. A structural representation of this ion pair cannot be specified precisely, but certainly there has been massive electron reorganization with little covalent interaction between the nuclei in the bond being broken. Mutual polarization of the carbonium ion and counter-ion can be assumed, as well as coulombic attraction. The intermediate formed in the rate-determining step is then rapidly converted to an intermediate which does involve covalent interaction with solvent or other nucleophiles present. Thus, the rate-determining step is unimolecular, and the observed kinetics are first-order. As will be seen shortly, the stereochemical course of the reaction can also be accommodated. 

Nucleophilic substitution reactions that follow second order kinetics and takes place in one step are called S 2 reactions. The rate determining step is the formation of intermediate transition state where both the reactant molecules undergo simultaneous covalency change, i.e., in an S 2 reaction, breaking of bond between the carbon atom and leaving nucleophile and making of bond between the carbon atom and incoming nucleophile occurs simultaneously. 

Using Si NMR and Raman spectroscopy, Jonas [68], Artaki et al. [81], and Zerda and Hoang [71] have investigated the hydrolysis of TMOS (pH - 5-7.5) at pressures up to 5 kbar. Their observations that pressure increases the rates of reaction without affecting the distributions of hydrolyzed and/or condensed species are consistent with an associative mechanism involving a pentacoordinate intermediate (transition-state volume, AF, is negative) rather than a dissociative mechanism in which the rate-determining step is the formation of a tricoordinated siliconium ion plus alcohol (AF positive). 

The picture of the process of substitution by the nitronium ion emerging from the facts discussed above is that of a two-stage process, the first step in which is rate-determining and which leads to a relatively stable intermediate. In the second step, which is relatively fast, the proton is lost. The transition state leading to the relatively stable intermediate is so constructed that in it the carbon-hydrogen bond which is finally broken is but little changed from its original condition. 

Even though the rearrangements suggest that discrete carbocation intermediates are involved, these reactions frequently show kinetics consistent with the presence of at least two hydrogen chloride molecules in the rate-determining transition state. A termolecular mechanism in which the second Itydrogen chloride molecule assists in the ionization of the electrophile has been suggested. ... 

For alkyl-substituted alkynes, there is a difference in stereochemistry between mono-and disubstituted derivatives. The former give syn addition whereas the latter react by anti addition. The disubstituted (internal) compounds are considerably ( 100 times) more reactive than the monosubstituted (terminal) ones. This result suggests that the transition state of the rate-determining step is stabilized by both of the alkyl substituents and points to a bridged intermediate. This would be consistent with the overall stereochemistry of the reaction for internal alkynes. 

The first step, which is rate determining, is an ionization to a carbocation (carbonium ion in earlier terminology) intermediate, which reacts with the nucleophile in the second step. Because the transition state for the rate-determining step includes R-X but not Y , the reaction is unimolecular and is labeled S l. First-order kinetics are involved, with the rate being independent of the nucleophile identity and concentration. 

The notion of concurrent SnI and Sn2 reactions has been invoked to account for kinetic observations in the presence of an added nucleophile and for heat capacities of activation,but the hypothesis is not strongly supported. Interpretations of borderline reactions in terms of one mechanism rather than two have been more widely accepted. Winstein et al. have proposed a classification of mechanisms according to the covalent participation by the solvent in the transition state of the rate-determining step. If such covalent interaction occurs, the reaction is assigned to the nucleophilic (N) class if covalent interaction is absent, the reaction is in the limiting (Lim) class. At their extremes these categories become equivalent to Sn and Sn , respectively, but the dividing line between Sn and Sn does not coincide with that between N and Lim. For example, a mass-law effect, which is evidence of an intermediate and therefore of the SnI mechanism, can be observed for some isopropyl compounds, but these appear to be in the N class in aqueous media. 

A large primary isotope effect kH/kD = 3.6 had also been found earlier by Ibne-Rasa122 in the nitrosation of 2,6-dibromophenol in the 4 position which was also shown to be base-catalysed. These values are not unexpected in view of the isotope effect found with diazonium coupling which involves a similarly unreactive electrophile, so that the rate-determining transition state will be displaced well towards products. Furthermore, the intermediate will have a quinonoid structure and will, therefore, be of low energy consequently, the energy barrier for the second step of the reaction will be high. 

In the above formulation the proton is transferred in the step in which the intermediate is formed. Such proton transfer is not essential for base catalysis. An alternate mode of catalysis is one in which the transition state for intermediate formation is a hydrogen-bonded complex, e.g. L, but in which this complex collapses to VI and the catalyst rather than to VIII. For such a formulation the only significant intermediate determining the rates would be VI, which would now be formed by the additional steps... 

On the basis of the examples given above, it is reasonable to suggest that the underlying principles for optimization of the overall reaction rate with respect to the choice of metal ion are similar. That is, there are basically three states along the reaction pathway which determine the most suitable choice of metal ion. These are (1) the reactant state with bound metal and substrate before the proton transfer step, (2) the intermediately created free OH nucleophile and, (3) the subsequent transition state associated with... 

The correct explanation of the peculiar behaviour of the butadiene-styrene system was provided by O Driscoll and Kuntz 144). As stated previously, under conditions of these experiments butadiene is indeed more reactive than styrene, whether towards lithium polystyrene or polybutadiene, contrary to a naive expectation. This was verified by Ells and Morton 1451 and by Worsfold 146,147) who determined the respective cross-propagation rate constants. It is germane to stress here that the coordination of the monomers with Li4, assumed to be the cause for this gradation of reactivities, takes place in the transition state of the addition and should be distinguished from the formation of an intermediate complex. The formation of a complex ... 

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