The Reactivity-Selectivity Postulate

The Hammond postulate is often accepted as a general principle an increase in reactivity is accompanied by a decrease in selectivity because the transition structure becomes closer to that of the reactant state as the energy barrier decreases. This idea has some truth for a hypothetical A to B reaction model where it is implicit that only a single bond change occurs moreover the Hammond postulate is predicted by the Marcus theory (above). The postulate often breaks down for reactions where more than one major bond change results in product formation. It should be emphasised that any discussion of the reactivity-selectivity relationship has to be confined to those reactions where there is no change in rate-limiting step or mechanism. 

The effect of variation in structure for example changing, the leaving group in the series fluoride, chloride, bromide, iodide and azide ion, has been used extensively in mechanistic studies but results should be viewed only in a confirmatory sense because the essentially gross structural change could cause equally gross mechanistic changes. The selectivity of the reaction between 2-substituted pyridines and methyl iodide appears 

The manifest linearity of the majority of free energy plots is paradoxical because the constant slope would indicate that the transition structure is substituent independent. Variation in structure might be expected to occur due to the change in substituent and thus yield curved relationships as indicated in Section 6.1. The relationship between reactivity and selectivity is based on a very simple model, to which most reactions do not conform because they involve not only at least two major bonding changes but solvation changes as well. 

The rate-limiting steps of many reactions are composed of several major, fundamental, bonding changes and hence it is not surprising that the transition structure is dependent on several variables. The elimination reaction (Equation 17) provides a useful example. 

The degree of proton transfer to the base in the transition structure is recorded as the Bronsted J3-value obtained by varying the structure of 

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Lewis and co-workers also are concerned with the reactivity-selectivity postulate (RSP), which can also be derived from the Marcus expression. In the examples given here, selectivity does not vary with reactivity, in apparent contradiction to Marcus theory. This result can be explained on the basis that the intrinsic barriers are not constant and by assuming that the quadratic term of the Marcus equation contributes very little when the identity barriers are high (as they are when rates are well below diffusion control). Other important contributions to understanding the RSP have been made recently (9a, 9b). 

Chemists have intuitively assumed for some time that selectivity is inversely related to reactivity. Thus a very fast reaction is likely to be less affected by substituents than is a slower one. There is at present considerable discussion as to the general validity of the reactivity-selectivity postulate (RSP) and Johnson [91] has indicated in his book that the linearity of the Hammett correlation is directly contrary to the postulate. The validity of the reactivity-selectivity postulate is directly related to that of Hammond (see later) which states that the structure of the transition state is closest to the state (ground or product) which has the highest potential energy. 

In other words, under these restrictive conditions, outer sphere electron-transfer reactions obeying the Marcus-Hush model are typical examples where the Hammond-Leffler postulate and the reactivity-selectivity principle (see, for example, Pross, 1977, and references cited therein, for the definition of these notions) are expected to apply. 

On the basis of the Leffler-Hammond postulate the theoretical justification for the reactivity-selectivity principle may be observed. First, let us define the selectivity 5, of a species A, in its reaction with two competing reagents X and Y, as indicated by (4), where k ... 

It is important to note that the above presentation, justifying the reactivity-selectivity principle, is based on a number of fundamental assumptions. First, it is assumed that the Leffler-Hammond postulate is valid, which in turn implies that the reaction under consideration obeys a rate-equilibrium relationship [eqn (2)]. This assumption often cannot be verified since for reactions of highly active species such as carbenes, free radicals, carbonium ions, etc., equilibrium constants are generally not measurable. However it follows that for reactions which do not conform to a rate-equilibrium relationship, no reactivity-selectivity relationship is expected. Also, in Fig. 4, the difference in the free energy of the... 

In spite of these uncertainties, however, the utility of the reactivity-selectivity principle has been illustrated for a number of diverse areas of mechanistic interest. Such applications are being extended to other areas as well. For example, Olah has recently studied the mechanism of electrophilic addition to multiple bonds using selectivity data and concluded that the transition states of the bromine addition to alkenes are of a 7r-complex nature (Olah and Hockswender, 1974). Finally the large number of reactivity-selectivity relationships which have been discovered offer considerable experimental support for the various expressions and formulations of the Hammond postulate whose profound effect on modem mechanistic chemistry is now beyond question. 

Leffler and reactivity-selectivity postulates, which predict that the selectivity should decrease and the Brpnsted (5 approach unity as the reactions become more endergonic. The curvature in this plot is much greater than predicted by the Marcus equation (equation 6) (22), however, and is believed to be an artifact caused by enhanced solvation of 7r-acceptor para substituents such as CN, COC6H5, and N02 (21). [The Marcus equation, which has gained wide acceptance in the interpretation of electron-transfer reactions, is represented in equation 6 as a Brpnsted relationship with an exponential term added to take into account curvature (23)]. 

The reactivity-selectivity relationship can be analyzed by postulating the following with respect to the reactants reactant A is designated as if it is highly... 

Physical organic chemistry has been built around LFER, which is still a matter of active research from experiment to theoretical simulation [53,54]. We ourselves have also addressed these problems under the perspective of the ISM [10,36a,42]. Here we will only deal with the interpretation of the Brpnsted relations, the postulate of Hammond and the Reactivity-Selectivity Principle (RSP). 

The reactivity-selectivity relationship can be analyzed by making the following postulations with respect to the reactants Reactant A is designated as Afj if it is highly reactive (hot) and as Ac if it is less reactive (cold), and the second reactant (which is also referred to as the substrate) is designated as B if it is more reactive and as 5 if less. Thus, the selectivity will vary depending on different combinations of A and B. 

Important differences are seen when the reactions of the other halogens are compared to bromination. In the case of chlorination, although the same chain mechanism is operative as for bromination, there is a key difference in the greatly diminished selectivity of the chlorination. For example, the pri sec selectivity in 2,3-dimethylbutane for chlorination is 1 3.6 in typical solvents. Because of the greater reactivity of the chlorine atom, abstractions of primary, secondary, and tertiary hydrogens are all exothermic. As a result of this exothermicity, the stability of the product radical has less influence on the activation energy. In terms of Hammond s postulate (Section 4.4.2), the transition state would be expected to be more reactant-like. As an example of the low selectivity, ethylbenzene is chlorinated at both the methyl and the methylene positions, despite the much greater stability of the benzyl radical ... 

In conclusion, bromination is a particularly attractive reaction for studying the origin of reactivity-selectivity effects in detail, since it is now well established that substituent and solvent effects arise not only from changes in the stability of the cationic intermediate but also from transition-state shifts, in agreement with the Bema Hapothle, i.e. RSP, Hammond postulate and Marcus effects. 

The influence of the classical anomeric effect and quasi-anomeric effect on the reactivity of various radicals has been probed. The isomer distribution for the deu-teriation of radical (48) was found to be selective whereas allylation was non-selective (Scheme 37). The results were explained by invoking a later transition state in the allylation, thus increasing the significance of thermodynamic control in the later reactions. Radical addition to a range of o -(arylsulfonyl)enones has been reported to give unexpected Pummerer rearrangement products (49) (Scheme 38).A mechanism has been postulated proceeding via the boron enolate followed by elimination of EtaBO anion. 

An efficient and selective Cu-assisted ortho-hydroxylation procedure for the conversion of benzoate to salicylate has been described, involving trimethylamine N-oxide (TMAO) as the oxidant [191,192]. The reaction was assumed to proceed via oxidation of a Cu carboxylate complex by TMAO to produce the active species (postulated to be a Cu hydroxo complex, but with only circumstantial evidence), followed by oxygen transfer to the benzoate group (Scheme 14). Using a set of different amide derivatives of benzoic acid, Comba and co-workers gained additional mechanistic hints in support of a reactive Cu-oxo or Cu-hydroxo intermediate that is stabilized by a five-membered chelate [193]. A pre-equilibrium involving Cu the ligand, and TMAO was proposed, but details of the reaction are far from clear. 

The reactive species generated by the photoexcitation of organic molecules in the electron-donor-acceptor systems are well established in last three decades as shown in Scheme 1. The reactivity of an exciplex and radical ion species is discussed in the following sections. The structure-reactivity relationship for the exciplexes, which possess infinite lifetimes and often emit their own fluorescence, has been shown in some selected regioselective and stereoselective photocycloadditions. However, the exciplex emission is often absent or too weak to be identified although the exciplexes are postulated in many photocycloadditions [11,12], The different reactivities among the contact radical ion pairs (polar exciplexes), solvent-separated radical ion pairs, and free-radical ions as ionic species... 

In line with the Leffler-Hammond postulate, which is a differential analogue of the Hammond postulate, the rationale for a differential reactivity-selectivity principle has been demonstrated, i.e., the marginal stabilization of a particular species will result in a corresponding increase in its selectivity. Recently, the view has been expressed that there is no substantive evidence for such behaviour... 

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