Nitration electrophilic aromatic substitution

Charge-transfer activation as the unifying theme in electrophilic aromatic substitution — nitration 237... 

The nitration, sulphonation and Friedel-Crafts acylation of aromatic compounds (e.g. benzene) are typical examples of electrophilic aromatic substitution. 

Nitration in sulphuric acid is a reaction for which the nature and concentrations of the electrophile, the nitronium ion, are well established. In these solutions compounds reacting one or two orders of magnitude faster than benzene do so at the rate of encounter of the aromatic molecules and the nitronium ion ( 2.5). If there were a connection between selectivity and reactivity in electrophilic aromatic substitutions, then electrophiles such as those operating in mercuration and Friedel-Crafts alkylation should be subject to control by encounter at a lower threshold of substrate reactivity than in nitration this does not appear to occur. 

Now that we ve outlined the general mechanism for electrophilic aromatic substitution we need only identify the specific electrophile m the nitration of benzene to have a fairly clear idea of how the reaction occurs... 

Figure 12 3 adapts the general mechanism of electrophilic aromatic substitution to the nitration of benzene The first step is rate determining m it benzene reacts with nitro mum ion to give the cyclohexadienyl cation intermediate In the second step the aro maticity of the ring is restored by loss of a proton from the cyclohexadienyl cation... 

Complexation of bromine with iron(III) bromide makes bromine more elec trophilic and it attacks benzene to give a cyclohexadienyl intermediate as shown m step 1 of the mechanism (Figure 12 6) In step 2 as m nitration and sulfonation loss of a proton from the cyclohexadienyl cation is rapid and gives the product of electrophilic aromatic substitution... 

Returning to Table 12 2 notice that halogen substituents direct an incoming electrophile to the ortho and para positions but deactivate the ring toward substitution Nitration of chlorobenzene is a typical example of electrophilic aromatic substitution m a halobenzene... 

Electrophilic aromatic substitution (Sec tion 22 14) Arylamines are very reac tive toward electrophilic aromatic sub stitution It IS customary to protect arylamines as their N acyl derivatives before carrying out ring nitration chio rination bromination sulfonation or Friedel-Crafts reactions... 

Other typical electrophilic aromatic substitution reactions—nitration (second entry) sul fonation (fourth entry) and Friedel-Crafts alkylation and acylation (fifth and sixth entnes)—take place readily and are synthetically useful Phenols also undergo elec trophilic substitution reactions that are limited to only the most active aromatic com pounds these include mtrosation (third entry) and coupling with diazomum salts (sev enth entry)... 

Nitration (Section 12 3) Replacement of a hydrogen by an —NO2 group The term is usually used in connection with electrophilic aromatic substitution... 

The active electrophile is formed by a subsequent reaction, often involving a Lewis acid. As discussed above with regard to nitration, the formation of the active electrophile may or may not be the rate-determining step. Scheme 10.1 indicates the structure of some of the electrophihc species that are involved in typical electrophilic aromatic substitution processes and the reactions involved in their formation. 

Because of Us high polarity and low nucleophilicity, a trifluoroacetic acid medium is usually used for the investigation of such carbocationic processes as solvolysis, protonation of alkenes, skeletal rearrangements, and hydride shifts [22-24] It also has been used for several synthetically useful reachons, such as electrophilic aromatic substitution [25], reductions [26, 27], and oxidations [28] Trifluoroacetic acid is a good medium for the nitration of aromatic compounds Nitration of benzene or toluene with sodium nitrate in trifluoroacetic acid is almost quantitative after 4 h at room temperature [25] Under these conditions, toluene gives the usual mixture of mononitrotoluenes in an o m p ratio of 61 6 2 6 35 8 A trifluoroacetic acid medium can be used for the reduction of acids, ketones, and alcohols with sodium borohydnde [26] or triethylsilane [27] Diary Iketones are smoothly reduced by sodium borohydnde in trifluoroacetic acid to diarylmethanes (equation 13)... 

Nitration by electrophilic aromatic substitution is not limited to benzene alone, but is a general reaction of compounds that contain a benzene ring. It would be a good idea to write out the answer to the following problem to ensure that you understand the relationship of starting materials to products in aromatic nitration before continuing to the next section. 

The hydroxyl group is a strongly activating, ortho- and para-directing substituent in electrophilic aromatic substitution reactions (Section 16.4). As a result, phenols are highly reactive substrates for electrophilic halogenation, nitration, sulfonation, and lTiedel-Crafts reactions. 

Unlike benzene, pyridine undergoes electrophilic aromatic substitution reactions with great difficulty. Halogenation can be carried out under drastic conditions, but nitration occurs in very low yield, and Friedel-Crafts reactions are not successful. Reactions usually give the 3-substituted product. 

First we will discuss reaction systems of the types shown here in which adducts were detected analytically and characterized as 7T-complexes. The idea of 7T-com-plexes as intermediates on the path to products of an electrophilic aromatic substitution was originally suggested by Dewar (1949). He did not, however, follow his hypothesis further. It was taken up again by Olah, particularly in relation to nitration (reviews Olah, 1971 Olah et al., 1987, 1989). 

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