Substitution, electrophilic selectivity relationship

The selectivity relationship merely expresses the proportionality between intermolecular and intramolecular selectivities in electrophilic substitution, and it is not surprising that these quantities should be related. There are examples of related reactions in which connections between selectivity and reactivity have been demonstrated. For example, the ratio of the rates of reaction with the azide anion and water of the triphenylmethyl, diphenylmethyl and tert-butyl carbonium ions were 2-8x10 , 2-4x10 and 3-9 respectively the selectivities of the ions decrease as the reactivities increase. The existence, under very restricted and closely related conditions, of a relationship between reactivity and selectivity in the reactions mentioned above, does not permit the assumption that a similar relationship holds over the wide range of different electrophilic aromatic substitutions. In these substitution reactions a difficulty arises in defining the concept of reactivity it is not sufficient to assume that the reactivity of an electrophile is related... 

One interesting proposal86 is that the encounter pair is a radical pair N02 ArH formed by an electron transfer (SET), which would explain why the electrophile, once in the encounter complex, can acquire the selectivity that the free N02+ lacked (it is not proposed that a radical pair is present in all aromatic substitutions only in those that do not obey the selectivity relationship). The radical pair subsequently collapses to the arenium ion. There is evidence87 both for and against this proposal.88... 

The observed effects of structure on rate and on orientation, confirmed by the Brown selectivity relationship, show that there is no basic difference between heterogeneous catalytic alkylation of aromatic compounds and homogeneous electrophilic aromatic substitution, cf. nitration, sul-phonation etc. This agreement allows the formulation of the alkylation mechanism as an electrophilic attack by carbonium ion-like species formed on the surface from the alkene on Br0nsted acidic sites. The state of the aromatic compound attacked is not clear it may react directly from the gas phase (Rideal mechanism ) [348] or be adsorbed weakly on the surface [359]. 

In 1956, as additional information was obtained for a range of substitution reactions, it was proposed that the linear relationship (8) be designated as the Selectivity Relationship (Brown and Smoot, 1956). The reactivity ratio, pfe/mfe, representing a measure of the discriminatory property of the electrophile, was employed to define the Selectivity Factor, 8t (9). In cases where the partial rate factors are not known, 8f... 

The Selectivity Relationship was shown to be applicable for substitution in the meta and para positions of toluene (Section II). The fine adherence of the -methyl group to a linear free-energy relationship (Fig. 37) is apparently typical of the behavior of the other alkyl substituents, as illustrated for the p-ethyl, p-i-propyl, and p-t-butyl groups (Figs. 38-40). Indeed, the data for electrophilic substitution in toluene are better correlated by a linear relationship than are the data for ordinary side-chain reactions of p-tolyl derivatives (Stock and Brown, 1959a). In the Extended Selectivity Treatment (Fig. 25) the side-chain reactions show a slightly greater scatter from the correlation line than the aromatic substitution reactions. 

The observations for the electrophilic substitution reactions of the monosubstituted benzenes have been examined for adherence to a linear free-energy relationship. As shown, the Selectivity Relationship,... 

Stock and Brown (1959) have carried out a detailed study of reactions involving the electrophilic substitution of hydrogen in toluene, and have shown that the selectivity relationship (eqs. (11), (20-23) of article by Stock and Brown) is applicable. 

Early examples of reactivity-selectivity relationships in aromatic substitutions are limited since, in the absence of absolute rate data, it is often difficult to assign relative reactivity to the different electrophiles. For certain cases where the relative reactivity order may be assumed, a reactivity-selectivity relationship was noted. For example, bromina-tion with the reactive species Br+ results in lower selectivity than with the less reactive species Br2 (de la Mare and Harvey, 1956 Brown, 1957). However, it appears that no general reactivity-selectivity relationship exists in electrophilic aromatic substitution reactions, for there exist slow, unselective reactions such as aromatic... 

More recently, Olah et al. (1970) have varied the reactivity of the electrophile in a systematic way and observed a number of convincing examples of reactivity- selectivity relationships. The Friedel-Crafts benzylation reaction on benzene and toluene was conducted for a large number of substituted benzyl chlorides. The data are in Table 18 and indicate that the selectivity of electrophilic attack decreases as the substituent becomes more electron withdrawing. 

Reactivity-selectivity relationships play an important part in free radical chemistry for the same reasons as in carbene chemistry and electrophilic substitution. Absolute rate constants for free radical reactions are not generally available (and when they are known they are often associated with large systematic errors), and the use of relative rate studies is an important technique in the study of free radical reactions. A comprehensive monograph dealing with various... 

Table IV compares the reactivity ratios of a soft (PhS-) to a hard (MeO-) nucleophile in vinylic substitution. PhS is always more reactive, and ratios lower than unity, as for 4, X = Br (4), are certainly due to elimination-addition with MeO . The ratios change by >2000-fold and are sensitive to the geometry of the substrate. An important feature is that for (3-halo-p-nitrostyrenes the ratio decreases strongly with the increased hardness of the (3-halogen (38). The lowest ratios are for the (3-fluoro derivative, whereas the differences between the chloro and bromo compounds are not so large. This behavior is similar to that in SNAr reactions. This behavior can be rationalized by symbiotic effects, which favor the soft-soft PhS--Br interaction and the hard-hard MeO-F interaction. A reactivity-selectivity relationship for vinyl bromides of different electrophilicities does not exist.

The selectivity of an electrophile, measured by the extent to which it discriminated either between benzene and toluene, or between the meta- and ara-positions in toluene, was considered to be related to its reactivity. Thus, powerful electrophiles, of which the species operating in Friedel-Crafts alkylation reactions were considered to be examples, would be less able to distinguish between compounds and positions than a weakly electrophilic reagent. The ultimate electrophilic species would be entirely insensitive to the differences between compounds and positions, and would bring about reaction in the statistical ratio of the various sites for substitution available to it. The idea has gained wide acceptance that the electrophiles operative in reactions which have low selectivity factors Sf) or reaction constants (p+), are intrinsically more reactive than the effective electrophiles in reactions which have higher values of these parameters. However, there are several aspects of this supposed relationship which merit discussion. 

Other matters that are important include the ability of the electrophile to select among the alternative positions on a substituted aromatic ring. The relative reactivity of different substituted benzenes toward various electrophiles has also been important in developing a firm understanding of electrophilic aromatic substitution. The next section considers some of the structure-reactivity relationships that have proven to be informative. 

At this point, attention can be given to specific electrophilic substitution reactions. The kinds of data that have been especially useful for determining mechanistic details include linear ffee-energy relationships, kinetic studies, isotope effects, and selectivity patterns. In general, the basic questions that need to be asked about each mechanism are (1) What is the active electrophile (2) Which step in the general mechanism for electrophilic aromatic substitution is rate-determining (3) What are the orientation and selectivity patterns ... 

Equation (7-85) is a selectivity-reactivity relationship, with lower values of Sf denoting lower selectivity. Lower values ofpt correspond to greater reactivity, with the limit being a partial rate factor of unity for an infinitely reactive electrophile. This selectivity-reactivity relationship is followed for the electrophilic substitution reactions of many substituted benzenes, although toluene is the best studied of these. 

Figs, 29—30. The relationship between logpK for electrophilic substitution and (29) the reaction constant, (30) the Selectivity Factor. (Fig. 30 reproduced by permission from Stock and Brown, J. Am. Chem. Soc. 84, 1242 (1962).)... 

Guideline 4 Some disubstituted compounds are also readily available and they may contain a relationship (especially ortho) that is difficult to achieve by electrophilic substitution. Here is a selection a supplier s catalogue will reveal more. 

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