Substitution, electrophilic with nitronium ions

Nitration of toluene is the only important reaction that involves the aromatic ring rather than the aliphatic methyl group. The nitration reaction occurs with an electrophilic substitution hy the nitronium ion. The reaction conditions are milder than those for henzene due to the activation of the ring hy the methyl substituent. A mixture of nitrotoluenes results. The two important monosubstituted nitrotoluenes are o- and p-nitrotoluenes ... 

Aniline is an important derivative of benzene that can be made in two steps by nitration to nitrobenzene and either catalytic hydrogenation or acidic metal reduction to aniline. Both steps occur in excellent yield. Almost all nitrobenzene manufactured (97%) is directly converted into aniline. The nitration of benzene with mixed acids is an example of an electrophilic aromatic substitution involving the nitronium ion as the attacking species. The hydrogenation of nitrobenzene has replaced the iron-... 

Figure 12.3 adapts the general mechanism of electrophilic aromatic substitution to the nitration of benzene. The first step is rate-determining in it benzene reacts with nitronium ion to give the cyclohexadienyl cation intermediate. In the second step, the aromaticity of the ring is restored by loss of a proton from the cyclohexadienyl cation. 

The question of the identity of the nitrating species can be approached by comparing selectivity with that of nitrations known to involve the nitronium ion. Examination of Part B of Table 9.8 shows that the position selectivity exhibited by acetyl nitrate toward toluene and ethylbenzene is not dramatically different from that observed with nitronium ion. The data for 2-propylbenzene suggest a higher o p ratio for nitronium ion nitrations, however. Several substituted aromatic compounds— for example, anisole and acetanilide — give much higher 0 p ratios when nitrated by acetyl nitrate than when nitronium ion conditions are used, suggesting the involvement of a different electrophile. ... 

When a positively charged substituent such as the trimethylam-monio group is anywhere on the ring, but most effectively when it is ortho to the leaving group, it can favorably affect the entropy of activation with anionic nucleophiles and accelerate reaction. A recent example of reagent-substituent interaction is the electrophilic substitution of 2-carboxybiphenyl, nitration (non-polar solvent) of which occurs only at the 2 -position and not the 4 -position and has been postulated to be due to the interaction of the nitronium ion with the carboxyl group. 

Similar to the alkylation and the chlorination of benzene, the nitration reaction is an electrophilic substitution of a benzene hydrogen (a proton) with a nitronium ion (NO ). The liquid-phase reaction occurs in presence of both concentrated nitric and sulfuric acids at approximately 50°C. Concentrated sulfuric acid has two functions it reacts with nitric acid to form the nitronium ion, and it absorbs the water formed during the reaction, which shifts the equilibrium to the formation of nitrobenzene ... 

Aromatic rings can be nitrated by reaction with a mixture of concentrated nitric and sulfuric acids. The electrophile is the nitronium ion, N02+, which is generated from HNO3 by protonation and loss of water. The nitronium ion reacts with benzene to yield a carbocation intermediate, and loss of H+ from this intermediate gives the neutral substitution product, nitrobenzene (Figure 16.4). 

Olah, G. A. Germain, A. Lin, H. C. Forsyth, D. Electrophilic reactions at Single Bonds. XVIII.1 Indication of Protosolvated de facto Substituting Agents in the Reactions of Alkanes with Acetylium and Nitronium Ions in Superacidic Media. J. Am. Chem. Soc. 1975, 97, 2928-2929. 

The simplest and most commonly used method of preparing nitric esters consists in the O-nitration reaction of alcohols with nitric acid, usually in the presence of sulphuric acid. The reaction is accompanied by reversible hydrolysis, which is typical of esterification reactions. It is very likely that the main nitrating agent is the nitronium ion NO (nitryl cation). It acts through electrophilic substitution. The presence of sulphuric and perchloric acids in the esterifying mixed acid favours the esterification, as it increases the concentration of NO ion. 

Nitration is widely applicable, can be carried out under a variety of conditions, can usually be stopped cleanly after mononitration, is usually effected by the nitronium ion, can take place on a neutral molecule or a cation, and in many cases can be considered as the standard aromatic electrophilic substitution. However, this last point must be treated with caution. Depending on the reaction conditions and reagents, the mechanism of the reaction does vary, and accompanying reactions such as oxidation (due to the oxidative action of nitric acid), acetoxylation (by acetyl nitrate), and migration of nitro groups following ipso attack (80MI1) can occur. Ipso nitration processes have been extensively studied by Fischer and co-workers. 

Another type of electrophilic substitution subject to microscopic diffusion control occurs when a highly reactive form of the substrate is produced in a pre-equilibrium step (e.g. by proton loss) and when this form reacts on encounter with the electrophile. The nitration of p-nitroaniline in 90% sulphuric acid appears to be a reaction of this type (Hartshorn and Ridd, 1968), although the short lifetime of the free amine complicates the mechanistic interpretation. The formulation in Scheme 1 fits this type of reaction provided A is taken to represent the protonated amine, X the free amine, and B the nitronium ion. In 90% sulphuric acid, the nitronium ion is the bulk component of the NOJ—HN03 equilibrium mixture. Many of the reactions in this review can be represented by Scheme f with some reservations concerning the lifetime of the intermediate X. 

As commonly accepted, the nitration of aromatic compounds is a typical reaction of electrophilic substitution, with the N02+ nitronium ion serving as a directly attacking moiety. On nitration by only nitric acid, the nitronium cation is formed via autoprotolysis according to Scheme 1 ... 

These steps illustrate how to generate the electrophile E for nitration and sulfonation, the process that begins any mechanism for electrophilic aromatic substitution. To complete either of these mechanisms, you must replace the electrophile by either or S03H in the general mechanism (Mechanism 18.1). Thus, the two-step sequence that replaces H by E is the same r ardless of E. This is shown in Sample Problem 18.1 u.sing the reaction of benzene with the nitronium ion. 

Nitroimidazoles are readily made by nitration of imidazole or 1-substituted imidazoles in concentrated sulfuric acid (see Section 7.2.1). It is much more difficult to make 2-nitroimidazoles since direct nitration is seldom observed in the 2-position. Although electrophilic nitrodehalogenation reactions, too, occur mainly at C-4(5) [1], Katritzky has recently selectively nitrodeiodinated 2,4,5-triiodoimidazole to prepare 2,4(5)-dinitro-5(4)-iodo-and 2,4,5-triiiitroimidazoles, albeit in poor yield [2], Other routes to 2-nitroimidazoles include those which react a diazonium fluoroborate with the nitrite ion, and methods which oxidize 2-amino derivatives, themselves often only available by laborious sequences. The most appealing routes to 2-nitroimidazoles are the methods which make the 2-lithio derivative and treat it with a source of nitronium ion (e.g. n-propyl nitrate or N2O4) [3-5] (see Section 7.2.2). 

The interaction of certain electrophiles with an aromatic ring leads to substitution. These electrophilic reactions involve a carbocation intermediate that gives up a stable, positively charged species (usually a proton) to a base to regenerate the aromatic ring. Typical electrophiles include chlorine and bromine (activated by interaction with a Lewis acid for all but highly reactive aromatic compounds), nitronium ion, SO3, the complexes of acid halides and anhydrides with Lewis acids (see Example 4.5) or the cations formed when such complexes decompose (R— —O or Ar =0), and carbocations. 

It appears that in nitration reactions the nitronium ion is sufficiently powerful as an electrophile to enable ring-substitution of the aryl azide to compete adequately with the decomposition pathway, and modest yields of nitroaryl azides may be achieved It is significant that... 

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