Nitration ipso attack

An ipso attack on the fluorine carbon position of 4-fIuorophenol at -40 °C affords 4-fluoro-4-nitrocyclohexa-2 5-dienone in addtion to 2-nitrophenol The cyclodienone slowly isomenzes to the 2-nitrophenol Although ipso nitration on 4-fluorophenyl acetate furnishes the same cyclodienone the major by-product is 4 fluoro-2,6-dinitrophenol [25] Under similar conditions, 4-fluoroanisole pnmar ily yields the 2-nitro isomer and 6% of the cyclodienone The isolated 2 nitro isomer IS postulated to form by attack of the nitromum ion ipso to the fluorine with concomitant capture of the incipient carbocation by acetic acid Loss of the elements of methyl acetate follows The nitrodienone, being the keto tautomer of the nitrophenol, aromatizes to the isolated product [26] (equation 20) Intramolecular capture of the intermediate carbocation occurs in nitration of 2-(4-fluorophenoxy)-2-methyIpropanoic acid at low temperature to give the spiro products 3 3-di-methyl-8 fluoro 8 nitro-1,4 dioxaspiro[4 5]deca 6,9 dien 2 one and the 10-nitro isomer [2d] (equation 21)... 

We have discussed orientation in the case of monosubstituted benzenes entirely in terms of attack at the ortho, meta, and para positions, but attack at the position bearing the substituent (called the ipsoposition ) can also be important. Ipso attack has mostly been studied for nitration. When NOj attacks at the ipso position there are at least five possible fates for the resulting arenium ion (13). 

Bromoanisole. The competition between ortho and ipso attack (83) is also pertinent to the simultaneous nitration and transbromination of 4-bromoani-sole (Perrin and Skimer, 1971). Charge-transfer nitration leads to mixture of 2-nitro-4-bromoanisole and 2,4-dibromoanisole (and 4-nitroanisole), the relative amounts of which are equivalent to those obtained in the electrophilic nitration of 4-bromoanisole. 

Methylanisole. The competition between ortho and ipso attack [analogous to that depicted in (83)] applies to the simultaneous nitration and demethyla-tion of 4-methylanisole. The identification of 4-nitro-4-methylcyclohexa-2,5-dienone as the metastable intermediate in charge-transfer nitration (Kim et al., 1993) is particularly diagnostic of the ipso adduct (84) that is also apparent in the electrophilic nitration of 4-methylanisole (Sankararaman and Kochi, 1991). The common bifurcation of nitration pathways resulting from para (ortho) and ipso attack on the various aromatic donors, as noted above, indicates that the activation step leading to the Wheland intermediate and... 

Nitro group rearrangements have also been postulated during aromatic nitration reactions, particularly those associated with reaction pathways involving ipso attack by the reagent (N02+ or NO2). This topic is more fully discussed elsewhere in this volume and so just a few examples will be presented here. 

Of necessity, only a few of the many papers published in this area have been examined in detail in this review. Clearly, the area of aromatic nitration is still full of surprises38 and ipso-attack of nitrating species on substituted aromatics is proving useful in elucidating many of the subtle mechanistic details37. 

The reaction of durene with H NOj under the conditions just mentioned is another specific but principally important case. The reaction is accompanied with a strong enhanced absorption in N NMR spectrum with respect to a signal belonging to the product, that is, nitrodurene. Durene and naphthalene have very similar standard potentials (2.07 and 2.08 V, respectively, in AN see Ridd 1991). A significant difference between them is that, with durene, much of the nitration supposedly arises from ipso attack followed by rearrangement according to Scheme 4.41. 

There are examples of ipso attack during the nitration of pyrroles, furans and thiophenes and in the corresponding benzo-fused systems. Reactions resulting in nitro-dealkylation, nitrodeacylation, nitro-decarboxylation and nitro-dehalogenation are to be found in the monograph reactivity chapters of CHEC. Treatment of the 3-azophenylindole (64) with nitric acid in acetic acid at room temperature gives 80% of the 3-nitroindole (65) (81JCS(P2)628). 

As mentioned in Section 3.14.2.4, one of the consequences of ipso attack could be side-chain functionalization. Examples of nitration and diazo coupling of a methyl group attached to thiophene are known. 

In general, orientation effects in the substitution of alkylbenzenes are complicated by ipso attack. For example, in the nitration of 4-methylisopropylbenzene (para-cymene) about 10% of the nitration product is 4-nitromethylbenzene ... 

The 4-nitromethy (benzene arises from ipso attack of NOW at the isopropyl-substituted ring carbon. Unlike methyl, the isopropyl group is eliminated rapidly as propene. Can we say that the other products, 3 and 4, arise by direct substitution Evidently not, because nitration at 0° gives two other products, 5 and 6, which must be formed by ipso attack at the inelhyl-heanng carbon. At low temperatures, intermediate ion 7 is attacked by the weakly nucleophilic ethanoate ion to give 5 and 6. Both of these adducts solvolyze rapidly in 78% sulfuric acid to give 3 only ... 

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. 

In the case of 5-bromo-3,4-dimethyl-l-phenyl-l/f, 6//-pyrano[2,3-c]pyrazol-6-one (59), mixed acid nitration results not only in para substitution in the phenyl ring, but also in ipso attack at the 5-position to yield... 

Earlier the presence of NO in nitric acid-hydrofluoric acid solution was postulated by Vorozhtsov Jr and his School [IS]. Vorozhtsov Jr and associates [19] found that nitric acid-hydrofluoric acid solution can produce both the nitration and (luorization of aromatic compounds through an ipso-attack (see p. 50) of both NO and F. ... 

The nitration of a number of anilines 172 in ca 70% sulfuric acid was reported as ipso-attack followed by a 1,3-rearrangement of the nitro group. The reaction occurs through the (pso-intermediate 173 to afford orf/zo-nitroaniline 174257 (equation 68). 

By use of H-ZSM-5 with a Si-to-Al ratio of 30 and boron ZSM-5, Salakhutdi-nov et al. [30] conducted the nitration of toluene with N2O4. No yields were reported, but boron ZSM-5 increased p-NT selectivity from 47 to 67 % at 125 °C. It was concluded that at elevated temperatures (> 125 °C) NB was formed in increasing amounts by dealkylation reactions after ipso attack of the aromatic compound by the nitronium ion. 

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