Intermediates in aromatic substitution

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. 

Ipso adducts. Ipso adducts as reactive intermediates in aromatic substitution are diagnostic of the electrophilic reactivity of the nitrating agent, particularly towards the following prototypical aromatic donors (Schofield, 1980 Olah et al., 1989). 

Benzyne produced from the zwitterion can also be captured by dienes in a Diels—Alder reaction (see Chapter 35). But this merely shows that benzyne can exist for a short time. It does not at all prove that benzyne is an intermediate in aromatic substitution reactions. Fortunately, there is very convincing evidence for this as well. 

The objective in the original application of this technique was to see if the arenonium intermediates in aromatic substitution are stable intermediates or, as Wheland had suggested, transition states. A study (see p. 316) of the rates of substitution in a number of aromatic AHs, combined with a PMO analysis, showed very clearly that arenonium ions or radicals are stable intermediates and also led to an explanation of the relation between the reactivity of reagents and their selectivity in substitution reactions. 

A great body of evidence supports the formulation of structure 38, as a key intermediate in aromatic substitution, although it is by no... 

It should be pointed out that the existence of stable structures of the intermediate-complex type (also known as a-complexes or Wheland complexes) is not of itself evidence for their being obligate intermediates in aromatic nucleophilic substitution. The lack of an element effect is suggested, but not established as in benzene derivatives (see Sections I,D,2 and II, D). The activated order of halogen reactivity F > Cl Br I has been observed in quantita-tivei36a,i37 Tables II, VII-XIII) and in many qualitative studies (see Section II, D). The reverse sequence applies to some less-activated compounds such as 3-halopyridines, but not in general.Bimolecular kinetics has been established by Chapman and others (Sections III, A and IV, A) for various reactions. 

In aromatic substitution of the electrophilic type, a cation or potential cation attacks the benzene ring. The transition state or intermediate, whichever it may be, has largely covalent bonds holding... 

Remarkable regioselectivity is exhibited in aromatic substitutions via aryne intermediates. When there is a donor group at the meta position, apparent ipso substitution occurs [24], The polarity alternation sequence indicates an electronic cause. 

Protonated polymethylbenzenes281 and the chlorohexamethylbenzenium cation,282 intermediates in aromatic electrophilic substitutions known as Wheland intermediates, have been isolated as crystalline salts, allowing investigators to obtain their X-ray crystal structure. Nitrosoarenium a complexes of various arenes were directly observed by transient absorption spectroscopy.283 Kochi presented a method combining appropriate instrumental techniques (X-ray crystallography, NMR, time-resolved UV-vis spectroscopy) for the observation, identification, and structural characterization of reactive intermediates fa and n complexes) in electrophilic aromatic substitution.284... 

Now, of course, the transition state in fact has a structure intermediate between the reactants and products the situation is the same as in aromatic substitution where the transition state lies between the reactants and the arenonium intermediate. This can be allowed for by an exactly similar procedure. If the bonds to atoms i, j are formed to an equal extent in the transition state, then... 

The fourteen alkaloids discussed in this section constitute a remarkable series of structurally and stereochemically interrelated substances. Superficially, all the alkaloids contain the same basic ring system, 5,10b-ethanophenanthridine (145), but alkaloids are elaborated from both enantiomorphs of this basic nucleus. Further variations are produced by differences in aromatic substitution and the functional groups attached to rings C.and D. It has been possible to interrelate all the alkaloids of this section through a combination of simple oxidation, reduction, and dehydration reactions coupled with four rather specific degradative techniques. These reactions are (1) aromatic demethoxylation by sodium and amyl alcohol (82), (2) replacement of OH by H via the action of lithium aluminum hydride on an intermediate chloro compound (146), (3) acid hydrolysis of ally lie methyl ethers to alcohols (147, 148), and (4) 0-methylation of hydroxylic alkaloids with... 

---