Reactivity determining step

It may seem, at first sight, paradoxical that a competition reaction carried out under conditions in which the measured rate is independent of the concentration of the aromatic can tell us about the relative reactivities of two aromatics. Obviously, the measured rate has nothing to do with the rate of the product-determining step, and what is important in determining relative reactivities is the ratio of the values of ( 3.2.4) for two compounds. The criteria to be met for a correct application of the competitive method are well understood. ... 

Both steps m this general mechanism are based on precedent It is called elec trophilic addition because the reaction is triggered by the attack of an acid acting as an electrophile on the rr electrons of the double bond Using the two rr electrons to form a bond to an electrophile generates a carbocation as a reactive intermediate normally this IS the rate determining step... 

As we have seen the nucleophile attacks the substrate m the rate determining step of the Sn2 mechanism it therefore follows that the rate of substitution may vary from nucleophile to nucleophile Just as some alkyl halides are more reactive than others some nucleophiles are more reactive than others Nucleophilic strength or nucleophilicity, is a measure of how fast a Lewis base displaces a leaving group from a suitable substrate By measuring the rate at which various Lewis bases react with methyl iodide m methanol a list of then nucleophihcities relative to methanol as the standard nucleophile has been compiled It is presented m Table 8 4... 

For most color photographic systems, development is the rate determining step, and within that step the formation of semiquinone is the slow process (37). The fate of the highly reactive QDI is deterrnined by the relative rates of a number of competing processes (38). The desired outcome is reaction with ionized coupler to produce dye (eq. 3). Typically, the second-order rate constant for this process with ionized coupler is about 10 to 10 ... 

Generally, the reactions of halopyrazines and haloquinoxalines with nucleophiles are believed to proceed by way of addition/elimination sequences, although there are clear-cut examples where this is not the case (see Section 2.14.2.2) and, consistent with a mechanism which involves bond forming, rather than bond breaking, reactions in the rate-determining step, fluoro derivatives are considerably more reactive ca. xlO ) than the corresponding chloro derivatives. 

The effect of conformation on reactivity is intimately associated with the details of the mechanism of a reaction. The examples of Scheme 3.2 illustrate some of the w s in which substituent orientation can affect reactivity. It has been shown that oxidation of cis-A-t-butylcyclohexanol is faster than oxidation of the trans isomer, but the rates of acetylation are in the opposite order. Let us consider the acetylation first. The rate of the reaction will depend on the fiee energy of activation for the rate-determining step. For acetylation, this step involves nucleophilic attack by the hydroxyl group on the acetic anhydride carbonyl... 

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. 

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. 

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. 

I > Br > Cl > F. In nucleophilic aromatic substitution, the formation of the addition intermediate is usually the rate-determining step so the ease of C—X bond breaking does not affeet the rate. When this is the ease, the order of reactivity is often F > Cl > Br > I. This order is the result of the polar effeet of the halogen. The stronger bond dipoles assoeiated with the more eleetronegative halogens favor the addition step and thus inerease the overall rate of reaetion. 

In this solvent the reaction is catalyzed by small amounts of trimethyl-amine and especially pyridine (cf. 9). The same effect occurs in the reaction of iV -methylaniline with 2-iV -methylanilino-4,6-dichloro-s-triazine. In benzene solution, the amine hydrochloride is so insoluble that the reaction could be followed by recovery. of the salt. However, this precluded study mider Bitter and Zollinger s conditions of catalysis by strong mineral acids in the sense of Banks (acid-base pre-equilibrium in solution). Instead, a new catalytic effect was revealed when the influence of organic acids was tested. This was assumed to depend on the bifunctional character of these catalysts, which act as both a proton donor and an acceptor in the transition state. In striking agreement with this conclusion, a-pyridone is very reactive and o-nitrophenol is not. Furthermore, since neither y-pyridone nor -nitrophenol are active, the structure of the catalyst must meet the conformational requirements for a cyclic transition state. Probably a concerted process involving structure 10 in the rate-determining step... 

If the rate-determining step were not a surface reaction but adsorption of competing reactants, we should obtain from the corresponding equations the expression which is formally identical with Eq. (15), in which, however, the relative reactivity is given by the expression S = fc dsA/ adsB. On the basis of data on competitive reactions only, these two cases cannot there-... 

The outstanding problem is to decide how much, if any, association exists between N02 and X" in the generally rate-determining step of the reaction. Kinetic studies tend to indicate the presence of different electrophiles under different conditions whereas the derived partial rate factors are closely similar and therefore indicate one electrophile common to most, if not all, nitrating agents. The more electron-attracting is X , the more easily is N02 displaced from it and hence a reactivity sequence should be... 

Finally, the brominations of mesitylene, 1,2,4,5-tetramethyl- and pentamethyl-benzene in chloroform (which is more polar than carbon tetrachloride) are first-order in bromine and iodine monobromide318, so that this is entirely consistent with the pattern developed above, i.e. the more polar the solvent and the more reactive the compound, the fewer the number of molecules of iodine monobromide that are involved in the rate-determining step. Measurements of rates between 25 and 42 °C revealed no significant trend owing to the variability of the rate coefficients determined at any temperature, but even so it is clear that there is no appreciable activation energy for these compounds, and there may have been temperature inversion for some of them. 

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