Nitration electrophilic

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)... 

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

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. 

Electrophilic nitration of a substituted benzene may lead to ortho, meta or para products, depending on the substituent. According to the Hammond Postulate, the kinetic product will be that which follows from the most stable intermediate benzenium ion, i.e. 

Predict the products of electrophilic nitration of toluene, aniline and nitrobenzene. 

Figure 16.4 The mechanism of electrophilic nitration of an aromatic ring. An electrostatic potential map of the reactive electrophile N02+ shows that the nitrogen atom is most positive (blue).

Figure 24.6 Electrophilic nitration of pyrrole. The intermediate produced by reaction at C2 is more stable than that produced by reaction at C3.

Recently, nitration of organolithiums and Grignards with N204 has been developed for the preparation of certain kinds of nitro compounds (Eqs. 2.14 and 2.15).31 The success of this process depends on the reaction conditions (low temperature) and the structure of substrates. For example, 3-nitrothiophene can be obtained in 70% overall yield from 3-bromothiophene this is far superior to the older method. 3-Nitroveratrole cannot be prepared usefully by classical electrophilic nitration of veratrole, but it can now be prepared by direct o>7/ o-lithiation followed by low-temperature N204 nitration. The mechanism is believed to proceed by dinitrogen tetroxide oxidation of the anion to a radical, followed by the radical s combination. 

The nitration of active methylene compounds generally proceeds via the reaction of carbanionic intermediates with an electrophilic nitrating agent such as alkyl nitrate (alkyl nitrate nitration). Details of this process are well documented in the reviews.38 The alkyl nitrate nitration method has been used extensively for the preparation of arylnitromethanes. The toluene derivatives, which have electron-withdrawing groups are nitrated with alkyl nitrates in the presence of KNH2 in liquid ammonia (Eqs. 2.19 and 2.20).39... 

Aromatic nitrosation with nitrosonium (NO + ) cation - unlike electrophilic nitration with nitronium (NO ) cation - is restricted to very reactive (electron-rich) substrates such as phenols and anilines.241 Electrophilic nitrosation with NO+ is estimated to be about 14 orders of magnitude less effective than nitration with N02+. 242 Such an unusually low reactivity of NO+ toward aromatic donors (as compared to that of NO ) is not a result of the different electron-acceptor strengths of these cationic acceptors since their (reversible) electrochemical reduction potentials are comparable. In order to pinpoint the origin of such a reactivity difference, let us examine the nitrosation reaction in the light of the donor-acceptor association and the electron-transfer paradigm as follows. 

As useful as tetranitromethane is as a charge-transfer nitrating agent, it is generally too unreactive to effect the comparable electrophilic nitration of most aromatic donors, except the most electron-rich ones. Thus in order to make the direct comparison between the photochemical and thermal nitration of the same ArH, we now turn to the A-nitropyridinium acceptor (PyNOj) as the alternative nitrating agent (Olah et al., 1965, 1980). For example, PyNO can be readily prepared as a colourless crystalline salt, free of any adventitious nitrosonium impurity, and used under essentially neutral conditions. Most importantly, the electrophilic reactivity of this... 

Mechanistic relevance of charge-transfer nitration to the electrophilic nitration of various aromatic donors... 

Thermal (electrophilic) and photochemical (charge-transfer) nitrations share in common the rapid, preequilibrium formation of the EDA complex [ArH, PyNO ]. Therefore let us consider how charge-transfer activation, as established by the kinetic behaviour of the reactive triad in Scheme 12, relates to a common mechanism for electrophilic nitration. Since the reactive intermediates pertinent to the thermal (electrophilic) process, unlike those in its photochemical counterpart, cannot be observed directly, we must rely initially on the unusual array of nonconventional nitration products (Hartshorn, 1974 Suzuki, 1977) and the unique isomeric distributions as follows. 

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... 

In view of the striking similarities that are consistently delineated in all three aspects dealing with (a) the isomeric product distributions, (b) nuclear versus side-chain nitration and (c) ipso adducts, the most direct formulation of electrophilic nitration invokes the production of the same intermediates (as those in the reactive triad in Scheme 10) via a purely thermal process (Scheme 19). 

Since the latter conditions pertain to aromatic nitration solely via the homolytic annihilation of the cation radical in Scheme 16, it follows from the isomeric distributions in (81) that the electrophilic nitrations of the less reactive aromatic donors (toluene, mesitylene, anisole, etc.) also proceed via Scheme 19. If so, why do the electrophilic and charge-transfer pathways diverge when the less reactive aromatic donors are treated with other /V-nitropyridinium reagents, particularly those derived from the electron-rich MeOPy and MePy The conundrum is cleanly resolved in Fig. 17, which shows the rate of homolytic annihilation of aromatic cation radicals by NO, (k2) to be singularly insensitive to cation-radical stability, as evaluated by x. By contrast, the rate of nucleophilic annihilation of ArH+- by pyridine (k2) shows a distinctive downward trend decreasing monotonically from toluene cation radical to anthracene cation radical. Indeed, the... 

Finally, we ask, if the reactive triads in Schemes 1 and 19 are common to both electrophilic and charge-transfer nitration, why is the nucleophilic pathway (k 2) apparently not pertinent to the electrophilic activation of toluene and anisole One obvious answer is that the electrophilic nitration of these less reactive [class (ii)] arenes proceeds via a different mechanism, in which N02 is directly transferred from V-nitropyridinium ion in a single step, without the intermediacy of the reactive triad, since such an activation process relates to the more conventional view of electrophilic aromatic substitution. However, the concerted mechanism for toluene, anisole, mesitylene, t-butylbenzene, etc., does not readily accommodate the three unique facets that relate charge-transfer directly to electrophilic nitration, viz., the lutidine syndrome, the added N02 effect, and the TFA neutralization (of Py). Accordingly, let us return to Schemes 10 and 19, and inquire into the nature of thermal (adiabatic) electron transfer in (87) vis-a-vis the (vertical) charge-transfer in (62). 

The electron-transfer mechanism for electrophilic aromatic nitration as presented in Scheme 19 is consistent with the CIDNP observation in related systems, in which the life-time of the radical pair [cf. (87)] is of particular concern (Kaptein, 1975 Clemens et al., 1984, 1985 Keumi et al., 1988 Morkovnik, 1988 Olah et al., 1989 Johnston et al., 1991 Ridd, 1991 Rudakov and Lobachev, 1991). As such, other types of experimental evidence for aromatic cation radicals as intermediates in electrophilic aromatic nitration are to be found only when there is significant competition from rate processes on the timescale of r<10 los. For example, the characteristic C-C bond scission of labile cation radicals is observed only during the electrophilic nitration of aromatic donors such as the dianthracenes and bicumene analogues which produce ArH+- with fragmentation rates of kf> 1010s-1 (Kim et al., 1992a,b). 

Since electrophilic and charge-transfer nitrations are both initiated via the same EDA complex and finally lead to the same array of nitration products, we infer that they share the intermediate stages in common. The strength of this inference rests on the variety of aromatic substrates (with widely differing reactivities and distinctive products) to establish the mechanistic criteria by which the identity of the two pathways are exhaustively tested. On this basis, electrophilic nitration is operationally equivalent to charge-transfer nitration in which electron-transfer activation is the obligatory first step. The extent to which the reactive triad in (90) is subject to intermolecu-lar interactions in the first interval (a few picoseconds) following electron transfer will, it is hoped, further define the mechanistic nuances of dissociative electron transfer in adiabatic and vertical systems (Shaik, 1991 Andrieux et al., 1992), especially when inner-sphere pathways are considered (Kochi, 1992). 

Electrophilic nitrations of aliphatic nitriles, carboxylic acids,carboxylic esters, ° and /3-diketones have been reported. The nitration of 2-alkyl-substituted indane-l,3-diones with nitric acid, followed by alkaline hydrolysis, is a standard laboratory route to primary nitroalkanes. ... 

While we believe our discussions of nitramine and nitrate ester synthesis to be comprehensive, it would be quite impossible to have a comprehensive discussion of aromatic nitration in this short chapter - published studies into aromatic nitration run into many tens of thousands. The purpose of this chapter is primarily to discuss the methods used for the synthesis of polynitroarylene explosives. Undoubtedly the most important and direct method for the synthesis of polynitroarylenes involves direct electrophilic nitration of the parent aromatic hydrocarbon. This work gives an overview of aromatic nitration but the discussion doesn t approach mechanistic studies in detail. Readers with more specialized interests in aromatic nitration are advised to consult several important works published in this area which give credit to this important reaction class.The use of polynitroarylenes as explosives and their detailed industrial synthesis has been expertly covered by Urbanski in Volumes 1 and 4 of Chemistry and Technology of Explosives ... 

Olah showed that nitrations can be split into the three categories of electrophilic, nucleophilic and free radical nitration. Free radical nitrations are extensively used for the industrial synthesis of low molecular weight nitroalkanes from aliphatic hydrocarbons. Nucleophilic nitration is the basis for a number of important methods for the synthesis of nitro and polynitro alkanes. Generally speaking only electrophilic nitration is of preparative importance for the... 

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