Electrophilic attack on aromatic

Functionalization of C—H bonds via aromatic substitution is an important means of adding functional groups to all kinds of arenes and as such is of significant relevance to many areas of chemistry. Notably, the key step in several industrially important reactions is an electrophilic attack on aromatic Jt-systems by carbocations or other strong electrophiles. 

There are only two reports of electrophilic attack on aromatic oxathioles. The cyclization of (62) in TFA generates the 1,3-oxathiolium (63), which cannot be isolated as such but which suffers acylation to give the stable derivative (64). It is unclear whether the nitrosation of thiapentalene (65) represents an electrophilic attack on the intact system or whether attack occurs on the ring-opened species (66). In the event, nitrosyl hexafluorophosphate... 

The formyl cation HCO+ (vco at 2110 cm ) is generated from CO under pressure in the presence of HF/SbFs. Concentrated sulfuric acid or the HCl/CuCl system, activates carbon monoxide toward the electrophilic attack on aromatic hydrocarbons to form aromatic aldehydes (Gatterman-Koch reaction). Branched carboxylic acids are obtained from alkenes and CO in the presence of concentrated sulfuric acid (Koch process) (equation 3). ... 

Because the position of electrophilic attack on an aromatic nng is controlled by the direct ing effects of substituents already present the preparation of disubstituted aromatic com pounds requires that careful thought be given to the order of introduction of the two groups Compare the independent preparations of m bromoacetophenone and p bromoace tophenone from benzene Both syntheses require a Friedel-Crafts acylation step and a bromination step but the major product is determined by the order m which the two steps are carried out When the meta directing acetyl group is introduced first the final product IS m bromoacetophenone... 

Having its pyrazolic 4-position substituted, electrophilic attack on indazoles takes place in the 3-position and in the homocycle (the 5- and 7-positions). The condensation of a benzene ring results in a decrease of the aromaticity of the pyrazole moiety, as in naphthalene compared to benzene, and therefore basic ring cleavage is easier in indazoles than in pyrazoles (Section 4.04.2.1.7(v)). 

As discussed in the theoretical section (4.04.1.2.1), electrophilic attack on pyrazoles takes place at C-4 in accordance with localization energies and tt-electron densities. Attack in other positions is extremely rare. This fact, added to the deactivating effect of the substituent introduced in the 4-position, explains why further electrophilic substitution is generally never observed. Indazole reacts at C-3, and reactions taking place on the fused ring will be discussed in Section 4.04.2.3.2(i). Reaction on the phenyl ring of C- and A-phenyl-pyrazoles will be discussed in Sections 4.04.2.3.3(ii) and 4.04.2.3.10(i), respectively. The behaviour of pyrazolones is quite different owing to the existence of a non-aromatic tautomer. 

Onium ions of small and large heterocyclics are usually produced by electrophilic attack on a heteroatom. In three- and four-membered rings nucleophilic attack on an adjacent carbon follows immediately, in most cases, and ring opening stabilizes the molecule. In large rings the onium ion behaves as would its acyclic analog, except where aromaticity or transannular reactions come into play (each with its electronic and steric pre-conditions). A wide diversity of reactions is observed. 

All these kinetic results can be accommodated by a general mechanism that incorporates the following fundamental components (1) complexation of the alkylating agent and the Lewis acid (2) electrophilic attack on the aromatic substrate to form the a-complex and (3) deprotonation. In many systems, there m be an ionization of the complex to yield a discrete carbocation. This step accounts for the fact that rearrangement of the alkyl group is frequently observed during Friedel-Crafts alkylation. 

Because the position of electrophilic attack on an aromatic ring is controlled by the dir ecting effects of substituents aheady present, the preparation of disubstituted aromatic compounds requires that careful thought be given to the order of introduction of the two groups. 

Draw and compare Lewis structures for benzene and pyridine. How many 7C electrons does each molecule have Where are the most accessible electrons in each Display the electrostatic potential map for pyridine and compare it to the corresponding map for benzene. Would you expect electrophilic attack on pyridine to occur analogously to that in benzene If so, should pyridine be more or less susceptible to aromatic substitution than benzene If not, where would you expect electrophilic attack to occur Explain. 

Intermodular Alkylation by Carbocations. The formation of carbon-carbon bonds by electrophilic attack on the ir system is a very important reaction in aromatic chemistry, with both Friedel-Crafts alkylation and acylation following this pattern. These reactions are discussed in Chapter 11. There also are useful reactions in which carbon-carbon bond formation results from electrophilic attack by a carbocation on an alkene. The reaction of a carbocation with an alkene to form a new carbon-carbon bond is both kinetically accessible and thermodynamically favorable. 

Where a starting material may be converted into two or more alternative products, e.g. in electrophilic attack on an aromatic species that already carries a substituent (p. 150), the proportions in which the alternative products are formed are often determined by their relative rate of formation the faster a product is formed the more of it there will be in the final product mixture this is known as kinetic control. This is not always what is observed however, for if one or more of the... 

Attack on aromatic species can occur with radicals, as well as with the electrophiles (p. 131) and nucleophiles (p. 167) that we have already considered as with these polar species, homolytic aromatic substitution proceeds by an addition/elimination pathway ... 

There is, however, no very satisfactory explanation of why such m-attack as does take place on QH5Y should also be faster than attack on QHg or of why attack on the o-position in C6H5Y is commonly faster than attack on the p-position. The relatively small spread of the partial rate factors for a particular QH5Y means that homolytic aromatic substitution normally leads to a more complex mixture of products than does electrophilic attack on the same species. 

To provide an example of a reaction that is very different to electrophilic aromatic substitution, the oxidation of formic acid by bromine was also studied. This reaction, which involves electrophilic attack on the formate anion (15) (Cox and McTigue, 1964 Smith, 1972 Herbine et al., 1980 Brusa and Colussi, 1980), is catalysed by a-CD (/c /k2u = 11) (Tee et al., 1990a), and the degree of transition state stabilization (Xts = 0.18 mM) is similar to that for phenols (Table A4.2) and most of the other substrates (Table A4.4). 

The reactivity of allenyl ketones is also manifested in the Hg(II)-catalyzed ipso substitution that converts 54 to spirodione 55 (Eq. 13.17) [19]. The reaction presumably involves activation of the allene by Hg(II), followed by intramolecular electrophilic attack on the aromatic ring. Hydrolytic cleavage of the metal from the intermediate product of the reaction, followed by rearrangement leads to the observed spirocyclic dione. 

The student should develop the mechanism of this reaction using the following stepwise information (1) protonation of the carbonyl (2) electrophilic attack on the aromatic ring (3) rearomatization by proton loss (4) another protonation, but then loss of a water molecule and (5) electrophilic attack and rearomatization. 

Treatment of the silyl compound, 61, above with hydrogen peroxide leads to the diol 62 which formally constitutes an oxidation as well as an electrophilic attack on the carbon atom. Classically, oxidation of nonconjugated rings to furnish their conjugated (usually aromatic) analogues is achieved by treatment with nickel(ii) peroxide however, these reactions are common and have been extensively explored for a number of different heterocyclic systems in both GHEC(1984) and CHEC-II(1996) so are not discussed further here. 

These equations show the general theoretical basis for the empirical order of rate constants given earlier for electrophilic attack on an aromatic ligand L, its metal complex ML, and its protonated form HL, one finds kt > n > hl. Conflicting reports in the literature state that coordination can both accelerate electrophilic aromatic substitution (30) and slow it down enormously (2). In the first case the rates of nitration of the diprotonated form of 0-phenanthroline and its Co(III) and Fe(III) complexes were compared. Here coordination prevents protonation in the mixed acid medium used for nitration and kML > h2l. In the second case the phenolate form of 8-hydroxyquinoline-5-sulfonic acid and its metal chelates were compared. The complexes underwent iodination much more slowly, if at all, and kL > kML ... 

The Friedel-Crafts alkylation of aromatic compounds by oxetanes in the presence of aluminum chloride is mechanistically similar to the solvolyses above, since the first step is electrophilic attack on the ring oxygen by aluminum chloride, followed by a nucleophilic attack on an a-carbon atom by the aromatic compound present. The reaction of 2-methyloxetane and 2-phenyloxetane with benzene, toluene and mesitylene gave 3-aryl-3 -methyl-1-propanols and 3-aryl-3-phenyl-l-propanols as the main products and in good yields (equation 27). Minor amounts of 3-chloro-l-butanol and 4-chloro-2-butanol are formed as by-products from 2-methyloxetane, and of 3-phenyl-l-propanol from 2-phenyloxetane (73ACS3944). 

Step (1) is reminiscent of electrophilic addition to an alkene. Aromatic substitution differs in that the intermediate carbocation (a benzenonium ion) loses a cation (most often to give the substitution product, rather than adding a nucleophile to give the addition product. The benzenonium ion is a specific example of an arenonium ion, formed by electrophilic attack on an arene (Section 11.4). It is also called a sigma complex, because it arises by formation of a o-bond between E and the ring. See Fig. 11-1 for a typical enthalpy-reaction curve for the nitration of an arene. 

Figure 6.40 Sites of electrophilic attack on guanine. PAHs are polycyclic aromatic hydrocarbons such as benzo(a)pyrene.

Photocycloadditions of higher order than 2 + 2) are sometimes encountered, but they are not so general as the (2 +2) reactions. Often they arise in reactions that occur by way of radical cations 2.83), when electrophilic attack on an aromatic ring may divert the reaction from cyclobutane formation, or in those that are promoted... 

---