Nitronium electrophile

Substitution reactions are characterized by the fact that a substrate reacts with a second molecule by incorporating the second molecule in its structure and hy releasing a part of the substrate. Substitution reactions can take place as electrophilic (see Section 2.2.5 for details), nucleophilic (Section 2.2.3), or radical suhstitu-tion reactions (Section 2.2.2) depending on the nature of the attacking reagent. Scheme 2.2.1 shows the electrophilic substitution of a hydrogen atom at henzene by the nitronium electrophile N02. This technically relevant reaction liberates a proton and forms nitrobenzene. It represents an important step in the synthesis of nitrobenzene, the key-intermediate for the production of aniline. 

Nitration can be effected under a wide variety of conditions, as already indicated. The characteristics and kinetics exhibited by the reactions depend on the reagents used, but, as the mechanisms have been elucidated, the surprising fact has emerged that the nitronium ion is preeminently effective as the electrophilic species. The evidence for the operation of other electrophiles will be discussed, but it can be said that the supremacy of one electrophile is uncharacteristic of electrophilic substitutions, and bestows on nitration great utility as a model reaction. 

In more dilute solutions the concentration of the nitronium ion falls below the level of spectroscopic detection, and the nature of the electrophilic species has been the subject of conjecture. 

Concentrated solutions are here considered to be those containing > c. 89 % by weight of sulphuric acid. In these solutions nitric acid is completely ionised to the nitronium ion. This fact, and the notion that the nitronium ion is the most powerful electrophilic nitrating species, makes operation of this species in these media seem probable. Evidence on this point comes from the effect on the rate of added water ( 2.4.2)... 

As the medium is still further diluted, until nitronium ion is not detectable, the second-order rate coefficient decreases by a factor of about 10 for each decrease of 10% in the concentration of the sulphuric acid (figs. 2.1, 2.3, 2.4). The active electrophile under these conditions is not molecular nitric acid because the variation in the rate is not similar to the correspondii chaise in the concentration of this species, determined by ultraviolet spectroscopy or measurements of the vapour pressure. " ... 

The results in table 2.6 show that the rates of reaction of compounds such as phenol and i-napthol are equal to the encounter rate. This observation is noteworthy because it shows that despite their potentially very high reactivity these compounds do not draw into reaction other electrophiles, and the nitronium ion remains solely effective. These particular instances illustrate an important general principle if by increasing the reactivity of the aromatic reactant in a substitution reaction, a plateau in rate constant for the reaction is achieved which can be identified as the rate constant for encounter of the reacting species, and if further structural modifications of the aromatic in the direction of further increasing its potential reactivity ultimately raise the rate constant above this plateau, then the incursion of a new electrophile must be admitted. 

For nitrations in sulphuric and perchloric acids an increase in the reactivity of the aromatic compound being nitrated beyond the level of about 38 times the reactivity of benzene cannot be detected. At this level, and with compounds which might be expected to surpass it, a roughly constant value of the second-order rate constant is found (table 2.6) because aromatic molecules and nitronium ions are reacting upon encounter. The encounter rate is measurable, and recognisable, because the concentration of the effective electrophile is so small. 

In the uncatalysed reaction the fact that added nitrate strongly accelerates the rate to the same extent as other salts makes it improbable that the nitronium ion is the effective electrophile. The authors of the work conclude that covalent dinitrogen pentoxide is the electrophilic... 

Further evidence that the nitronium ion was not the electrophile in the uncatalysed reaction, and yet became effective in the catalysed reaction, came from differences in the orientation of substitution. The nitration of chlorobenzene in the uncatalysed reaction yielded only 43 % of the para compound, whereas, when the catalysed reaction was made important by adding some nitric acid, the ratio of substitution was that usually observed in nitration involving the nitronium ion ( 5.3.4). In the case of the uncatalysed reaction however, the reaction was complicated by the formation of nitrophenols. 

It has been necessary to comment upon these various studies because Olah and his co-workers have suggested that whilst nitrations, like those with nitronium salts, which give a relative rate of reaction of toluene with respect to benzene not much greater than unity involve the nitronium ion as the electrophile, this is not so in other cases. It is important to consider these opinions closely. In the earlier of the two relevant papers it is agreed that since nitrations of toluene with nitronium tetrafluoroborate in sulpholan show no abnormal o -ratio there... 

The nitronium ion is the electrophile in nitrations with nitronium salts in organic solvents. 

In other systems electrophiles other than the nitronium ion are involved with activated substrates (in these cases intermolecular selectivity is high, whereas with nitronium salts it is low). 

Another reason for discussing the mechanism of nitration in these media separately from that in inert organic solvents is that, as indicated above, the nature of the electrophile is not established, and has been the subject of controversy. The cases for the involvement of acetyl nitrate, protonated acetyl nitrate, dinitrogen pentoxide and the nitronium ion have been advocated. 

In earlier chapters we have been concerned with the identification of the effective electrophile in nitrations carried out under various conditions. We have seen that very commonly the nitronium ion is the electrophile, though dinitrogen pentoxide seems capable of assuming this role. We now consider how the electrophile, specifically the nitronium ion, reacts with the aromatic compound to cause nitration. 

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. 

From these results it appears that the 5-position of thiazole is two to three more reactive than the 4-position, that methylation in the 2-position enhances the rate of nitration by a factor of 15 in the 5-position and of 8 in the 4-position, that this last factor is 10 and 14 for 2-Et and 2-t-Bu groups, respectively. Asato (374) and Dou (375) arrived at the same figure for the orientation of the nitration of 2-methyl and 2-propylthiazole Asato used nitronium fluoroborate and the dinitrogen tetroxide-boron trifluoride complex at room temperature, and Dou used sulfonitric acid at 70°C (Table T54). About the same proportion of 4-and 5-isomers was obtained in the nitration of 2-methoxythiazole by Friedmann (376). Recently, Katritzky et al. (377) presented the first kinetic studies of electrophilic substitution in thiazoles the nitration of thiazoles and thiazolones (Table 1-55). The reaction was followed spec-trophotometrically and performed at different acidities by varying the... 

Aliphatic Nitration. Alkanes undergo electrophilic nitration with nitronium salts such as (N02) piotic solvent such as CH2CI2... 

The general mechanistic framework outlined in this section must be elaborated by other details to fully describe the mechanisms of the individual electrophilic substitutions. The question of the identity of the active electrophile in each reaction is important. We have discussed the case of nitration, in which, under many circumstances, the electrophile is the nitronium ion. Similar questions arise in most of the other substitution reactions. 

Nitronium fluorosulfate in fluorosulfonic acid adds electrophilically across the double bond offluoroolefins in a nonspecific manner. Tnfluorochloroethylene reacts accordingly with nitronium fluorosulfate to give a 2.1 mixture of regio-isomers [7] (equation 7). Under these reaction conditions perfluoropropylene is unreactive even after extended heating at 80 C 2-Nitroperfluoropropyl fluorosulfate is obtained on treatment of the perfluoropropylene with nitronium fluorosulfate in antimony pentafluoride [5] (equation 8). 

Tnflic acid is an excellent catalyst for the nitration of aromatic compounds [.S7]. In a mixture with nitnc acid, it forms the highly electrophilic nitronium inflate, which can be isolated as a white crystalline solid Nitronium inflate is a powerful nitrating reagent in inert organie solvents and in tnflic acid or sulfuric acid. It nitrates benzene, toluene, chlorobenzene, nitrobenzene, m-xylene, and benzotn-fluoride quantitatively in the temperature range of-110 to 30 °C with exeeptionally high positional selectivity [87],... 

The electrophile (E" ) in this reaction is nitronirim ion ( 0=N=0 ). The charge distribution in nitronium ion is evident both in its Lewis structure and in the electrostatic potential map of Figure 12.2. There we see the complementar y relationship between the electron-poor region near- nitrogen of NO, and the electron-rich region associated with the TT electrons of benzene. 

Equation (1-3) is an aromatic electrophilic substitution (Se), the nitronium ion being the electrophile and the proton the leaving group (electrafuge). 

Electrostatic potential map for nitronium cation shows most positively-charged regions (in blue) as likely electrophilic sites. 

Among the most common and synthetically-usef electrophiles are nitronium and acyl cations, NO2+ at CH3CO+, respectively. The former is the active agent electrophilic nitration while the latter is the active reage in Friedel-Crafts acylation. 

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 ... 

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 ... 

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). 

With ten 7i-electrons delocalized over seven atoms, trithiadiazepine is electron rich and should undergo electrophilic substitution, which indeed it does. Nitronium tetrafluoroborate at — 10 C or copper(II) nitrate gives the mononitro derivative 5, which can be converted into the dinitro compound 6 by the action of an excess of nitronium tetrafluoroborate at 10 C.388... 

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