Mechanism of nitration

The observation already discussed ( 2.2, 2.3, 2.4) of nitrations, in concentrated and aqueous mineral acids and in pure nitric acid, which depend on the first power of the concentration of the aromatic compound, does not help much in elucidating the mechanisms of nitrations under these conditions. In contrast, the observation of zeroth-order... 

In contrast to its effect upon the general mechanism of nitration by the nitronium ion, nitrous acid catalyses the nitration of phenol, aniline, and related compounds. Some of these compounds are oxidised under the conditions of reaction and the consequent formation of more nitrous acids leads to autocatalysis. 

The kinetics of nitration of anisole in solutions of nitric acid in acetic acid were complicated, for both autocatalysis and autoretardation could be observed under suitable conditions. However, it was concluded from these results that two mechanisms of nitration were operating, namely the general mechanism involving the nitronium ion and the reaction catalysed by nitrous acid. It was not possible to isolate these mechanisms completely, although by varying the conditions either could be made dominant. 

The catalysis was very strong, for in the absence of nitrous acid nitration was very slow. The rate of the catalysed reaction increased steeply with the concentration of nitric acid, but not as steeply as the zeroth-order rate of nitration, for at high acidities the general nitronium ion mechanism of nitration intervened. 

Under the conditions mentioned, i-methylnaphthalene was nitrated appreciably faster than was mesitylene, and the nitration was strongly catalysed by nitrous acid. The mere fact of reaction at a rate greater than the encounter rate demonstrates the incursion of a new mechanism of nitration, and its characteristics identify it as nitration via nitrosation. 

The results of Olah and his co-workers require, then, no special hypothesis regarding mechanism of nitration, in so far as they relate to... 

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. 

Because of the chemical similarity between benzoyl nitrate and the acetyl nitrate which is formed in solutions of nitric acid in acetic anhydride, it is tempting to draw analogies between the mechanisms of nitration in such solutions and in solutions of benzoyl nitrate in carbon tetrachloride. Similarities do exist, such as the production by these reagents of higher proportions of o-substituted products from some substrates than are produced by nitronium ions, as already mentioned and further discussed below. Further, in solutions in carbon tetrachloride of acetyl nitrate or benzoyl nitrate, the addition of acetic anhydride and benzoic anhydride respectively reduces the rate of reaction, implying that dinitrogen pentoxide may also be involved in nitration in acetic anhydride. However, for solutions in which acetic anhydride is also the solvent, the analogy should be drawn with caution, for in many ways the conditions are not comparable. Thus, carbon tetrachloride is a non-polar solvent, in which, as has been shown above,... 

The evidence outlined strongly suggests that nitration via nitrosation accompanies the general mechanism of nitration in these media in the reactions of very reactive compounds.i Proof that phenol, even in solutions prepared from pure nitric acid, underwent nitration by a special mechanism came from examining rates of reaction of phenol and mesi-tylene under zeroth-order conditions. The variation in the initial rates with the concentration of aromatic (fig. 5.2) shows that mesitylene (o-2-0 4 mol 1 ) reacts at the zeroth-order rate, whereas phenol is nitrated considerably faster by a process which is first order in the concentration of aromatic. It is noteworthy that in these solutions the concentration of nitrous acid was below the level of detection (< c. 5 X mol... 

Despite the fact that solutions of acetyl nitrate prepared from purified nitric acid contained no detectable nitrous acid, the sensitivity of the rates of nitration of very reactive compounds to nitrous acid demonstrated in this work is so great that concentrations of nitrous acid below the detectable level could produce considerable catalytic effects. However, because the concentration of nitrous acid in these solutions is unknown the possibility cannot absolutely be excluded that the special mechanism is nitration by a relatively unreactive electrophile. Whatever the nature of the supervenient reaction, it is clear that there is at least a dichotomy in the mechanism of nitration for very reactive compounds, and that, unless the contributions of the separate mechanisms can be distinguished, quantitative comparisons of reactivity are meaningless. 

The mechanisms of nitration with acetyl nitrate in acetic anhydride... 

By analogy with the mechanisms of nitration in other media, and from a knowledge of the composition of solutions of acetyl nitrate in acetic anhydride, the following may be considered possible nitrating species in these solutions ... 

Thus, strong arguments against all of the obvious nitrating species acting alone can be found. However, as has been pointed out, the extent to which ions require solvation by nitric acid molecules in this medium is unknown, and such solvation would influence the apparent order with respect to the stoichiometric nitric acid. The possibility also exists that more than one mechanism of nitration, excluding nitrosation, is operative. 

Because of these difficulties, special mechanisms were proposed for the 4-nitrations of 2,6-lutidine i-oxide and quinoline i-oxide, and for the nitration of the weakly basic anilines.However, recent remeasurements of the temperature coefficient of Hq, and use of the new values in the above calculations reconciles experimental and calculated activation parameters and so removes difficulties in the way of accepting the mechanisms of nitration as involving the very small equilibrium concentrations of the free bases. Despite this resolution of the difficulty some problems about these reactions do remain, especially when the very short life times of the molecules of unprotonated amines in nitration solutions are considered... 

As has been noted above, there is no gross change in the mechanism of nitration of PhNH3+ down to 82 % sulphuric acid. The increase in o- andp-substitution at lower acidities has been attributed differential salt effects upon nitration at the individual positions. The two sets of partial rate factors quoted for PhNH3+ in table 9.3 show the effect of the substituent on the Gibbs function of activation at the m- and -positions to be roughly equal for reaction in 98 % sulphuric acid, and about 28 % greater at the -position in 82 % sulphuric acid. ... 

The precise mechanism of nitrate action is not cleady understood and may be a combination of many factors. The basic pharmacologic action of nitrates is a relaxation of most vascular smooth muscle, eg, vascular, bronchial, gastrointestinal, uretal, uterine, etc. Vascular smooth muscle relaxation is a... 

Nitration of 3-phenyl-1,2-benzisoxazole with fuming nitric acid has been shown to give dinitro products of undetermined substitution pattern (67AHC(8)277, p. 290>. However, more satisfactory studies have now been described, especially on the kinetics and mechanism of nitration of 3-methyl-l,2-benzisoxazole (77JCS(P2)47). Nitration in cold, concentrated mixed acids yields the 5-nitro derivative exclusively, nitration in 80-90% sulfuric acid occurring on the free base whereas at higher acidities the conjugate acid is the species involved in the nitration. 

T. Urbadski, Chemistry and Technology of Explosives , Vols 1, 2 3 (Refs 74, 75 82), an excellent presentation of the prepn, properties and chemistry of nitrated compds and the technology and mechanisms of nitrations... 

L.F. Albright C. Hansen, Eds, Industrial and Laboratory Nitrations , ACS Symposium Series 22, ACS, Washington, DC (1976). Excellent modern review. Ten chapters emphasize various aspects of the chemistry and mechanism of nitrations, including oxidation and ipso-nitration side reactions. Six chapters discuss the chemistry and physical transfer steps between phases. Eight chapters discuss plant operation-improvements, safety features, and new operations. The final chapter is devoted to vapor phase nitrations... 

These theories are reviewed in Urbanski (Ref 74, pp53—60). Modern views of the mechanism of nitration will be examined in detail in Section VIII... 

Summary. Modern views of the mechanism of nitration are divided into two schools. 

It should be pointed out that most of the evidence presented above in support of the ni-tronium ion or free radical mechanisms of nitration was obtained with homogeneous solns under conditions that cannot be compared directly with the conditions prevailing in industrial nitrations... 

The general mechanism of nitrating alcohols to form nitrate esters is described under Nitration in this Vol. Several specific remarks about PETN are contained in that article. The industrial nitration of PE differs from most nitrate esters in that it employs coned nitric acid rather than mixed acid. Nevertheless nitration via the nitronium ion mechanism, which is the preferred mechanism in mixed acid nitrations, is also feasible in coned nitric acid. However, Eremenko and co-workers claim that the nitrating agent in PE nitrations, in mixed acid, is unionized nitric acid (Refs 39 76). The present writer does not find Eremenko s arguments to be very convincing. In any case, commercial production of PETN employs nitric acid and not the mixed acids of Eremenko s studies... 

For instance, nitration of naphthalene, azulene, biphenylene, and triphenylene proceeds preferentially in positions with the greatest constant of hyperfine splitting at the hydrogen atom in ESR spectra of corresponding cation-radicals. The constant is known to be proportional to the spin density on the carbon atom bearing the mentioned hydrogen. It is important, however, that the same orientation is also observed at classical mechanism of nitration in cases of naphthalene, azulene, and biphenylene, but not triphenylene (see Todres 1985). 

Fung HE and Bauer JA. Mechanisms of nitrate tolerance. Cardiovasc Drug Ther 1994 8 489. 

The kinetics and mechanisms of nitrate radical reactions with alkanes and a variety of other organics relevant to the atmosphere are discussed in detail in two excellent reviews by Wayne et al. (1991) and Atkinson (1991). The kinetics of the N03-alkane reactions are summarized in Table 6.3, where it can be seen that, with the exception of methane, they are in the range 10 lX-10 lf cm3 molecule-1 s-1. 

Investigation of the mechanism of nitrate reduction by Desulfovibrio desulfuricans nitrate reductase at various levels of theory has confirmed the utility of the orbital-free embedding method in the description of enzymatic processes.379... 

Titov, A.I. 1963. The free radical mechanism of nitration. Tetrahedron 19 557-580. 

Schofield (80MI1) has provided a comprehensive review of aromatic nitration but with slight emphasis on phenyl heterocycles. There have also been extensive reviews of the methods and mechanisms of nitration... 

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