And Wheland intermediates

The overall mechanism shown in Scheme 2, outlined by Shilov at an early stage in the research, has been essentially vahdated by all subsequent work. The reaction begins with activation of a C-H bond at a Pt(II) center. (There are examples of arene, but not alkane, activation by Pt(lV) these probably involve classical electrophihc routes via 7i-complexes and Wheland intermediates [10].) This fact seems incontrovertible since Pt(ll) by itself catalyzes H/D exchange the detailed mechanism of the activation is much less obvious, as discussed in Sect. 3. The resulting RPt(II) complex is extremely sensitive to electrophilic cleavage - no [RPt Cl c(H20)3 J species can be observed in the presence of any protmi source - so using Pt(II) alone, no alkane conversion beyond isotopic exchange would be feasible. However, [Pt Cle] effects oxidation to RPt(IV), which is virtually completely inert to protonolysis but quite susceptible to nucleophilic... 

Wheland intermediate (see below) as its model for the transition state. In this form it is illustrated by the case mentioned above, that of nitration of the phenyltrimethylammonium ion. For this case the transition state for -nitration is represented by (v) and that for p-substitution by (vi). It is argued that electrostatic repulsions in the former are smaller than in the latter, so that m-nitration is favoured, though it is associated rvith deactivation. Similar descriptions can be given for the gross effects of other substituents upon orientation. 

However, the existence of the Wheland intermediate is not demanded by the evidence, for if the attack of the electrophile and the loss of the proton were synchronous an isotope effect would also be expected. The... 

Thompson points out that there is no evidence that adducts give other than acetates on thermolysis. The exocyclic methylene intermediate (iv) postulated by Robinson could arise by proton abstraction from a Wheland intermediate analogous to (vll) above, rather than from the adduct (in). Similarly its decomposition does not necessarily require the intermediacy of the adduct (v). The fact that i -methyl-4-nitromethylnaphthalene is the product even when the nitrating medium is nitric acid and nitromethane would then require no separate explanation. 

Significantly, the pre-exponential factors decrease with increasing reactivity, and this suggests that the Wheland intermediate is more nearly formed in the transition state, the more reactive the compound. Or, considered another way, the position along the reaction co-ordinate at which a given amount of carbon-halogen bond formation occurs is nearer to the ground state the more reactive the compound. 

The textbook definition of a reactive intermediate is a short-lived, high-energy, highly reactive molecule that determines the outcome of a chemical reaction. Well-known examples are radicals and carbenes such species cannot be isolated in general, but are usually postulated as part of a reaction mechanism, and evidence for their existence is usually indirect. In thermal reactivity, for example, the Wheland intermediate (Scheme 9.1) is a key intermediate in aromatic substitution. 

The validity of Wheland intermediates such as (18) and (20) in Friedel-Crafts alkylation has been established by the actual isolation... 

What we shall be doing in the discussion that follows is comparing the effect that a particular Y would be expected to have on the rate of attack on positions o-/p- and m-, respectively, to the substituent Y. This assumes that the proportions of isomers formed are determined entirely by their relative rates of formation, i.e. that the control is wholly kinetic (cf. p. 163). Strictly we should seek to compare the effect of Y on the different transition states for o-, m- and p-attack, but this is not usually possible. Instead we shall use Wheland intermediates as models for the transition states that immediately precede them in the rate-limiting step, just as we have done already in discussing the individual electrophilic substitution reactions (cf. p. 136). It will be convenient to discuss several different types of Y in turn. 

After what we have seen to date, it surely comes as no great surprise to find that the ratio of o- to p-product obtained from substitution of C6H5Y, where Y is o-/p-directing, is seldom, if ever, the statistical ratio of 2 1. There is found to be very close agreement between calculation and n.m.r. data for the distribution of +ve charge—p-> o- m—around the ring in the cyclohexadienyl cation (57), which is the Wheland intermediate for proton exchange in benzene (cf. p. 133) ... 

With naphthalene, electrophilic substitution (e.g. nitration) is found to take place preferentially at the 1- (a-), rather than the alternative 2- (/ -), position. This can be accounted for by the more effective delocalisation, and hence stabilisation, that can take place in the Wheland intermediate for 1 - attack (60a - 606) compared with that for 2-attack (61) ... 

Pyridine is thus referred to as a n-deficient heterocycle and, by analogy with a benzene ring that carries an electron-withdrawing substituent, e.g. N02 (p. 151), one would expect it to be deactivated towards electrophilic attack. Substitution takes place, with difficulty, at the 3-position because this leads to the most stable Wheland intermediate (63) the intermediates for 2- and 4-attack (64 and 65, respectively) each has a canonical state in which the charge is located on divalent N—a highly unstable, i.e. high energy, state ... 

It is to be expected that attack by nucleophiles on an unsubstituted benzene nucleus will be much more difficult than attack by electrophiles. This is so (o) because the n electron cloud of the nucleus (p. 130) is likely to repel an approaching nucleophile, and (b) because its n orbital system is much less capable of delocalising (and so stabilising) the two extra electrons in the negatively charged (72), than the positively charged Wheland intermediate (73) ... 

The subsequent, spontaneous fragmentation of the nitropyridinyl radical and the collapse of the ion-radical pair to the Wheland intermediate (followed by rapid deprotonation) completes the nitration, i.e.,... 

Fig. 20 Deconvolution of the transient spectrum obtained upon the application of a 25-ps laser pulse to a solution of [hexamethylbenzene, NO+] charge-transfer complex showing the Wheland intermediate (430 nm) and the hexamethylbenzene cation radical (495 nm). Courtesy of S.M. Hubig and J.K. Kochi, unpublished results.

The formation of the Wheland intermediate from the ion-radical pair as the critical reactive intermediate is common in both nitration and nitrosation processes. However, the contrasting reactivity trend in various nitrosation reactions with NO + (as well as the observation of substantial kinetic deuterium isotope effects) is ascribed to a rate-limiting deprotonation of the reversibly formed Wheland intermediate. In the case of aromatic nitration with NO, deprotonation is fast and occurs with no kinetic (deuterium) isotope effect. However, the nitrosoarenes (unlike their nitro counterparts) are excellent electron donors as judged by their low oxidation potentials as compared to parent arene.246 As a result, nitrosoarenes are also much better Bronsted bases249 than the corresponding nitro derivatives, and this marked distinction readily accounts for the large differentiation in the deprotonation rates of their respective conjugate acids (i.e., Wheland intermediates). 

Temporal evolution of aromatic cation radicals to the Wheland intermediate and the nucleophilic adduct in charge-transfer nitration... 

The observation of second-order kinetics (ku) for the spectral decay of the anisole cation radical in Fig. 15 points to the disappearance of AN + - after its separation from the initially formed triad in (63). Owing to the high yields of nitroanisoles obtained, such a process can be formulated as in Scheme 11 as the bimolecular (homolytic) reaction in (64) that produces the critical Wheland intermediate in aromatic nitration according to Perrin (1977) and Ridd (1991). 

AN+- (Reitstoen and Parker, 1991). In other words, the triad of reactive fragments produced in (63) in the charge-transfer excitation of the EDA complex with A-nitropyridinium ion is susceptible to mutual (pairwise) annihilations leading to the Wheland intermediate W and the nucleophilic adduct N (Scheme 12), so that the observed second-order rate constant ku for the spectral decay of ArH+- in Table 3 actually represents a composite of k2 and k2. A similar competition between the homolytic and nucleophilic reactivity of aromatic cation radicals is observed in the reaction triad (55)... 

The triad annihilations in Schemes 12 and 13 again provide the mechanistic basis for analysing these apparently disparate results. Thus the difference between Me2PyN02 and MeOPyNOj in (i) and (ii), respectively, mirrors that observed for toluene (vide supra). Accordingly, the statistical ortho/ para pattern obtained from Me2PyN02 in (i) can be attributed to a similar dominance of the homolytic annihilation of AN+- to produce the critical Wheland intermediate in aromatic nitration (Scheme 17). Indeed, the... 

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