Kinetics rate determining step

This observation is consistent with the assumptions of the authors predicting microwave effects when the polarity is enhanced in a dipolar TS. The kinetic rate-determining step consists of an intramolecular attack of the nitrogen lone pair on the carbon atom of the carbonyl moiety (Scheme 3.15). 

The noticeable rate enhancement due to a microwave-specific effect is consistent with a reaction mechanism in which the kinetic rate-determining step is nucleophilic attack of an amino group on the chloroquinoline ring (Scheme 3.16). 

The Sj l reaction mechanism and kinetics. Rate-determining step... 

The treatment may be made more detailed by supposing that the rate-determining step is actually from species O in the OHP (at potential relative to the solution) to species R similarly located. The effect is to make fi dependent on the value of 2 and hence on any changes in the electrical double layer. This type of analysis has permitted some detailed interpretations to be made of kinetic schemes for electrode reactions and also connects that subject to the general one of this chapter. 

Melander first sought for a kinetic isotope effect in aromatic nitration he nitrated tritiobenzene, and several other compounds, in mixed acid and found the tritium to be replaced at the same rate as protium (table 6.1). Whilst the result shows only that the hydrogen is not appreciably loosened in the transition state of the rate-determining step, it is most easily understood in terms of the S 2 mechanism with... 

Hughes and Ingold interpreted second order kinetic behavior to mean that the rate determining step is bimolecular that is that both hydroxide ion and methyl bromide are involved at the transition state The symbol given to the detailed description of the mech anism that they developed is 8 2 standing for substitution nucleophilic bimolecular... 

Each act of proton abstraction from the a carbon converts a chiral molecule to an achi ral enol or enolate ion The sp hybridized carbon that is the chirality center m the start mg ketone becomes sp hybridized m the enol or enolate Careful kinetic studies have established that the rate of loss of optical activity of sec butyl phenyl ketone is equal to Its rate of hydrogen-deuterium exchange its rate of brommation and its rate of lodma tion In each case the rate determining step is conversion of the starting ketone to the enol or enolate anion... 

Overall the reaction exhibits second order kinetics Both the ester and the base are involved m the rate determining step or m a rapid step that precedes it... 

Second order kinetics is usually interpreted m terms of a bimolecular rate determining step In this case then we look for a mechanism m which both the aryl halide and the nucleophile are involved m the slowest step Such a mechanism is described m the fol lowing section... 

Kinetics As the observation of second order kinetics requires the rate determining step (step 1) involves both the aryl halide and the nucleophile... 

Until now we have been discussing the kinetics of catalyzed reactions. Losses due to volatility and side reactions also raise questions as to the validity of assuming a constant concentration of catalyst. Of course, one way of avoiding this issue is to omit an outside catalyst reactions involving carboxylic acids can be catalyzed by these compounds themselves. Experiments conducted under these conditions are informative in their own right and not merely as means of eliminating errors in the catalyzed case. As noted in connection with the discussion of reaction (5.G), the intermediate is stabilized by coordination with a proton from the catalyst. In the case of autoprotolysis by the carboxylic acid reactant, the rate-determining step is probably the slow reaction of intermediate [1] ... 

The course of the reaction is dependent on the configuration of the oxime. The (Z)-oxime gave 1,2-benzisoxazoles as the primary product while the (E)-oxime generally produced a Beckmann rearrangement product with or without subsequent cyclization to a benzisoxazole (Scheme 167) (67AHC(8)277). Bunnett conducted a kinetic study on the reaction shown in Scheme 167 and determined that cyclization to intermediate (551) was the rate determining step (61JA3805). 

The goal of a kinetic study is to establish the quantitative relationship between the concentration of reactants and catalysts and the rate of the reaction. Typically, such a study involves rate measurements at enough different concentrations of each reactant so that the kinetic order with respect to each reactant can be assessed. A complete investigation allows the reaction to be described by a rate law, which is an algebraic expression containing one or more rate constants as well as the concentrations of all reactants that are involved in the rate-determining step and steps prior to the rate-determining step. Each concentration has an exponent, which is the order of the reaction with respect to that component. The overall kinetic order of the reaction is the sum of all the exponents in the... 

Kinetic data provide information only about the rate-determining step and steps preceding it. In the hypothetical reaction under consideration, the final step follows the rate-determining step, and because its rate will not affect the rate of the overall reaction, will not appear in the overall rate expression. The rate of the overall reaction is governed by the second step, which is the bottleneck in the process. The rate of this step is equal to A2 multiplied by the molar concentration of intermediate C, which may not be directly measurable. It is therefore necessary to express the rate in terms of the concentrations of reactants. In the case under consideration, this can be done by recognizing that [C] is related to [A] and [B] by an equilibrium constant ... 

These examples illustrate the relationship between kinetic results and the determination of reaction mechanism. Kinetic results can exclude from consideration all mechanisms that require a rate law different from the observed one. It is often true, however, that related mechanisms give rise to identical predicted rate expressions. In this case, the mechanisms are kinetically equivalent, and a choice between them is not possible on the basis of kinetic data. A further limitation on the information that kinetic studies provide should also be recognized. Although the data can give the composition of the activated complex for the rate-determining step and preceding steps, it provides no information about the structure of the intermediate. Sometimes the structure can be inferred from related chemical experience, but it is never established by kinetic data alone. 

A special type of substituent effect which has proved veiy valuable in the study of reaction mechanisms is the replacement of an atom by one of its isotopes. Isotopic substitution most often involves replacing protium by deuterium (or tritium) but is applicable to nuclei other than hydrogen. The quantitative differences are largest, however, for hydrogen, because its isotopes have the largest relative mass differences. Isotopic substitution usually has no effect on the qualitative chemical reactivity of the substrate, but often has an easily measured effect on the rate at which reaction occurs. Let us consider how this modification of the rate arises. Initially, the discussion will concern primary kinetic isotope effects, those in which a bond to the isotopically substituted atom is broken in the rate-determining step. We will use C—H bonds as the specific topic of discussion, but the same concepts apply for other elements. 

The details of proton-transfer processes can also be probed by examination of solvent isotope effects, for example, by comparing the rates of a reaction in H2O versus D2O. The solvent isotope effect can be either normal or inverse, depending on the nature of the proton-transfer process in the reaction mechanism. D3O+ is a stronger acid than H3O+. As a result, reactants in D2O solution are somewhat more extensively protonated than in H2O at identical acid concentration. A reaction that involves a rapid equilibrium protonation will proceed faster in D2O than in H2O because of the higher concentration of the protonated reactant. On the other hand, if proton transfer is part of the rate-determining step, the reaction will be faster in H2O than in D2O because of the normal primary kinetic isotope effect of the type considered in Section 4.5. 

Kinetic studies of the addition of hydrogen chloride to styrene support the conclusion that an ion-pair mechanism operates because aromatic conjugation is involved. The reaction is first-order in hydrogen chloride, indicating that only one molecule of hydrogen chloride participates in the rate-determining step. ... 

A number of studies of the acid-catalyzed mechanism of enolization have been done. The case of cyclohexanone is illustrative. The reaction is catalyzed by various carboxylic acids and substituted ammonium ions. The effectiveness of these proton donors as catalysts correlates with their pK values. When plotted according to the Bronsted catalysis law (Section 4.8), the value of the slope a is 0.74. When deuterium or tritium is introduced in the a position, there is a marked decrease in the rate of acid-catalyzed enolization h/ d 5. This kinetic isotope effect indicates that the C—H bond cleavage is part of the rate-determining step. The generally accepted mechanism for acid-catalyzed enolization pictures the rate-determining step as deprotonation of the protonated ketone ... 

TWo types of rate expressions have been found to describe the kinetics of most aromatic nitration reactions. With relatively unreactive substrates, second-order kinetics, first-order in the nitrating reagent and first-order in the aromatic, are observed. This second-order relationship corresponds to rate-limiting attack of the electrophile on the aromatic reactant. With more reactive aromatics, this step can be faster than formation of the active electrq)hile. When formation of the active electrophile is the rate-determining step, the concentration of the aromatic reactant no longer appears in the observed rate expression. Under these conditions, different aromatic substrates undergo nitration at the same rate, corresponding to the rate of formation of the active electrophile. 

Enolization is the rate-determining step in the halogenation of normal ketones. Where alternate directions for enolization exist, the preferred direction (and hence the position of kinetic bromination) depends on the substituents and stereochemistry. Furthermore, the orientation of the bromine introduced depends on stereochemical and stereoelectronic factors. 

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