Rate profile for nitration

Fig. 2.1. Rate profiles for nitration in 80-100% sulphuric acid. For references see table 3.3.

Fig. 3.3. Rate profiles for nitration at 25 °C corrected for variation in activity coefficients. ...

For this series of compounds qualitative information is quite extensive. Application of the criteria discussed in 8.2, in particular comparison with the corresponding methyl quaternary salt, establishment of the rate profile for nitration in sulphuric acid, and consideration of the encounter rate and activation parameters, shows that 2,4,6-collidine is nitrated as its cation. The same is true for the 3-nitration of 2,4- ... 

A useful general assessment of nitration of a range of substrates in aqueous nitric acid has been presented/ which has centered on the rate profile for nitration in nitric acid, the limiting rate of nitration when reaction occurs on encounter, and the rate of reaction of nitronium ions with the solvent. In this work hydrazine was added when necessary to prevent catalysis by nitrous acid. New Raman data on nitric acid and d-nitric acid have been reported. ... 

There are certain limitations to the usefulness of nitration in aqueous sulphuric acid. Because of the behaviour of the rate profile for benzene, comparisons should strictly be made below 68% sulphuric acid ( 2.5 fig. 2.5) rates relative to benzene vary in the range 68-80% sulphuric acid, and at the higher end of this range are not entirely measures of relative reactivity. For deactivated compounds this limitation is not very important, but for activated compounds it is linked with a fundamental limit to the significance of the concept of aromatic reactivity as already discussed ( 2.5), nitration in sulphuric acid cannot differentiate amongst compounds not less than about 38 times more reactive than benzene. At this point differentiation disappears because reactions occur at the encounter rate. 

Further problems arise if measurements of the rate of nitration have been made at temperatures other than 25 °C under these circumstances two procedures are feasible. The first is discussed in 8.2.2 below. In the second the rate profile for the compound imder investigation is corrected to 25 °C by use of the Arrhenius parameters, and then further corrected for protonation to give the calculated value of logio/i fb. at 25 °C, and thus the calculated rate profile for the free base at 25 °C. The obvious disadvantage is the inaccuracy which arises from the Arrhenius extrapolation, and the fact that, as mentioned above, it is not always known which acidity functions are appropriate. 

This method is exemplified by its application to quinoline, isoquinoline, cinnoline, and isoquinoline 2-oxide, which are nitrated as their conjugate acids. The rate profiles for these compounds and their N- or O-methyl perchlorates show closely parallel dependences upon acidity (fig. 2.4). Quaternisation had in each case only a small effect upon the rate, making the criterion a very reliable one. It has the additional advantage of being applicable at any temperature for which kinetic measurements can be made (table 8.1, sections B and D). 

The similarity of their rate profiles, and the similarity of their rate constants for nitration at a particular temperature and acidity show that 4-pyridone, i-methyl-4-pyridone, and 4-methoxypyridine are all nitrated as their cations down to about 85 % sulphuric acid. The same is true of 2-methoxy-3-methylpyridine. In contrast, 3- and 5-methyl-2-pyridone, i,5-dimethyl-2-pyridone and 3-nitro-4-pyridone all react... 

A comparison of the second-order rate coefficients for nitration of 2,4,6-tri-methylpyridine and 1,2,4,6-tetramethylpyridinium ion (both at the 3-position) shows similarity of profile in the common acidity region and a rapidly increasing rate with acidity for the trimethyl compound at acidities below 90 wt. % (where the usual maximum is obtained). These two pieces of evidence show reaction to occur on the conjugate acid as also indicated by the large negative entropy of activation. Surprisingly, the tetramethyl compound is less reactive than the trimethyl compound so maybe this is an example of steric hindrance to solvation. Calculation of the encounter rate also showed that reaction on the free base was unlikely. 

By contrast, the rate-acidity profiles for nitration of 3-nitro-4-pyridone, 3-and 5-methyl-2-pyridone and l,5-dimethyl-2-pyridone resemble each other and differ from the above-indicated reaction upon the free base, and correction of the observed rates to allow for the concentration of free base actually present gave rate-acidity profiles of the expected form the corrected entropies of activation then turned out to be positive. Furthermore, if the logarithms of the corrected rate coefficients obtained in media of low acidity were plotted against +log aHlQ, then slopes of near unity were obtained (see above, p. 18), but not otherwise. A similar result was obtained from the nitration data for 4-pyridone in media of low acidity suggesting that here it reacts as the free base. A further test which was applied was to calculate the concentration of nitronium ions in the various media and to correct the observed rate coefficients for this the logarithms of these coeffi-... 

Figure 1 Rate profiles for the nitration of (a) 2,6-dimethoxypyridine (x = 3) and (b) 2,6-dimethoxy-3-nitropyridine ( = 5.5)...

The data available for —130 compounds were processed in this way to derive the standard rate coefficients [75J(P2) 1600]. Note that when nitration occurs at more than one position, the slope of the rate profile refers to the overall reaction. Standard rate coefficients for nitrations at the individual positions are then obtained using the isomer distribution at the measured acidity nearest to 75 wt% H2S04. When nitration occurs at two or more equivalent positions, the calculated log k% values refer to overall reactivity, and must therefore be statistically corrected. 

Generally the determination of the reactivity of a particular compound depends upon comparison of its rate of nitration with that of benzene at the same acidity and temperature. Because of the spread of rates this may not be practically possible and, in any case, is usually not necessary because of the parallelism existing among rate profiles (fig. 2.4). Reactivities in aqueous sulphuric acid are, in fact, very nearly independent of acidity, and stepwise comparison of data for a compound with those of benzene determined at different acidities is possible. 

For deactivated compounds this limitation does not exist, and nitration in sulphuric acid is an excellent method for comparing the reactivities of such compounds. For these, however, there remains the practical difficulty of following slow reactions and the possibility that with such reactions secondary processes might become important. With deactivated compounds, comparisons of reactivities can be made using nitration in concentrated sulphuric acid such comparisons are not accurate because of the behaviour of rate profiles at high acidities ( 2.3.2 figs. 2.1, 2.3). 

Similar difficulties arise in the nitrations of 2-chloro-4-nitroaniline and /)-nitroaniline. Consideration of the rate profiles and orientation of nitration ( 8.2.5) these compounds suggests that nitration involves the free bases. However, the concentrations of the latter are so small as to imply that if they are involved reaction between the amines and the nitronium ion must occur upon encounter that being so, the observed activation energies appear to be too high. The activation energy for the simple nitration of the free base in the case of/>-nitroaniline was calculated from the following equation ... 

The interest attaching to the nitration of pyridine i-oxide and its derivatives has already been mentioned ( 8.2.5). Some data for these reactions are given in tables 8.1, 8.2 and 8.4. The 4-nitration of pyridine I-oxide is shown to occur through the free base by comparison with the case of i-methoxypyridinium cation ( 8.2.2), by the nature of the rate profile ( 8.2.1), and by consideration of the encounter rate ( 8.2.3). - Some of these criteria have been used to show that the same is true for... 

TABLE in-45. RATE PROFILE SLOPES FOR NITRATION OF THIAZOLE (242)... 

In the section dealing with electrophilic attack at carbon some results on indazole homocyclic reactivity were presented nitration at position 5 (Section 4.04.2.1.4(ii)), sulfon-ation at position 7 (Section 4.04.2.1.4(iii)) and bromination at positions 5 and 7 (Section 4.04.2.1.4(v)). The orientation depends on the nature (cationic, neutral or anionic) of the indazole. Protonation, for instance, deactivates the heterocycle and directs the attack towards the fused benzene ring. A careful study of the nitration of indazoles at positions 2, 3, 5 or 7 has been published by Habraken (7UOC3084) who described the synthesis of several dinitroindazoles (5,7 5,6 3,5 3,6 3,4 3,7). The kinetics of the nitration of indazole to form the 5-nitro derivative have been determined (72JCS(P2)632). The rate profile at acidities below 90% sulfuric acid shows that the reaction involves the conjugate acid of indazole. 

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