Wheland intermediates

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... 

A different explanation of the high 0 -ratios is based on the view, for which there is some evidence, that in a transition state for substitution which resembles the Wheland intermediate in structure there is a larger positive charge at the - than at the o-position. Substituents of the present type would therefore stabilise the transition state more from the 0-than from the -position. ... 

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. 

As the o-complexes in these azo coupling reactions are steady-state intermediates (Wheland intermediates, named after Wheland s suggestion in 1942), their stereochemistry cannot be determined directly. Bent structures like that in Figure 12-6 can, however, be isolated in electrophilic substitutions of 1,3,5-triaminobenzene... 

Wheland intermediate 357 see also Azo coupling reaction, o-complex Wolff rearrangement 80f., 281, 284ff. Woodward-Hoffmann rules 129, 361, 396... 

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 ... 

Electrophilic substitution of pyrrole can, however, be carried out under specialised conditions (e.g. acylation with (MeC0)20/BF3, sulphonation with a pyridine/S03 complex, C5H5N-S03, cf. (67)) leading to preferential attack at the 2-, rather than the 3-, position. This reflects the slightly greater stabilisation of the Wheland intermediate for the former (70) compared with that for the latter (71) ... 

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.,... 

---