Nitration of bases

Arrhenius parameters, and nitration of bases, 155-9 for nitration of aza-naphthalenes, 209-11... 

Conditions A, nitrate of base added to H2SO4 solution of base in H2SO4 added to KNO3. 

Many aromatic compounds are sufficiently basic to be appreciably protonated in concentrated sulphuric acid. If nitration occurs substantially through the free base, then the reactivity of the conjugate acid will be negligible. Therefore, increasii the acidity of the medium will, by depleting the concentration of the free base, reduce the rateof reaction. This probably accounts for the particularly marked fall in rate which occurs in the nitration of anthraquinone, benzoic acid, benzenesulphonic acid, and some nitroanilines (see table 2.4). 

The value of the second-order rate constant for nitration of benzene-sulphonic acid in anhydrous sulphuric acid varies with the concentration of the aromatic substrate and with that of additives such as nitromethane and sulphuryl chloride. The effect seems to depend on the total concentration of non-electrolyte, moderate values of which (up to about 0-5 mol 1 ) depress the rate constant. More substantial concentrations of non-electrolytes can cause marked rate enhancements in this medium. Added hydrogen sulphate salts or bases such as pyridine... 

If the concentration of effective aromatic species does vary with acidity, as sometimes happens if the compound is substantially proto-nated, then the acidity-dependence of the rate will be less steep than usual, because the concentration of the active free base diminishes significantly with increasing acidity. This situation has been observed in certain cases ( 8.2). The fall in the concentration of the active species can be allowed for from a knowledge of its pK and the acidity function which, for the particular compound, gives the best measure of the acidity of the medium. Then the corrected acidity-dependence of the rate resembles that observed with compounds the concentration of which does not change significantly with acidity. The nitration of minor species is discussed later ( 8.2). 

Another circumstance which could change the most commonly observed characteristics of the two-stage process of substitution has already been mentioned it is that in which the step in which the proton is lost is retarded because of a low concentration of base. Such an effect has not been observed in aromatic nitration ( 6.2.2), but it is interesting to note that it occurs in A -nitration. The A -nitration of A -methyl-2,4,6-trinitroaniline does not show a deuterium isotope effect in dilute sulphuric acid but does so in more concentrated solutions (> 60 % sulphuric acid kjj/kjj = 4 8). ... 

Comparison of the rate of nitration of the base with that of a necessarily cationic derivative. 

TABLE 8.2 The acidity dependence of rates of nitration of some free bases in sulphuric acid... 

An alternative approach is to assume, in the light of the experimental evidence just mentioned, that the reactions of cations and neutral molecules have similar values of (or, equivalently, of log ( /l mol and to try to calculate the difference which would arise from the fact that the observed entropy of activation for a minority free base includes a contribution from the acidic dissociation of the conjugate acid in the medium in question (see (5) above). Consider the two following reaction schemes one (primed symbols) represents nitration via the free base, the other the normal nitration of a non-basic majority species (unprimed symbols) ... 

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 ... 

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... 

For the nitration of the very weak base, acetophenone, there is reasonable agreement between observed and calculated activation parameters, and there is no doubt that nitration of the free base occurs at acidities below that of maximum rate. In this case the equilibrium concentration of free base is much greater than in the examples just discussed and there is no question of reaction upon encounter. ... 

Using the partial rate factors for nitration of chlorobenzene, Ridd and de la Mare calculated the relative rates of nitration of the dichlorobenzenes, with respect to /)-dichlorobenzene, with the results shown below. Also given are results based on more recent nitrations in mixed... 

The 2-nitration of 3-hydroxy- and 3-methoxy-pyridine in 85-96% sulphuric acid involves the conjugate acids, whilst the 3-nitration of 6-hydroxy and 6-methoxy-2-pyridone in 70-77 % sulphuric acid involves the free bases, which react at, or near to the encounter rate. ... 

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... 

A more detailed study of the nitration of quinolinium (l) in 80-05 % sulphuric acid at 25 °C, using isotopic dilution analysis, has shown that 3-) 5-) 6-, 7- and 8-nitroquinoline are formed (table 10.3). Combining these results with the kinetic ones, and assuming that no 2- and 4-nitration occurs, gives the partial rate factors listed in table 10.4. Isoquinolinium is 14 times more reactive than quinolinium. The strong deactivation of the 3-position is in accord with an estimated partial rate factor of io for hydrogen isotope exchange at the 3-position in the pyridinium ion. It has been estimated that the reactivity of this ion is at least 10 less than that of the quinolinium ion. Based on this estimate, the partial rate factor for 3-nitration of the pyridinium ion would be less than 5 x io . 

Comparison of the behaviour of cinnoline 2-oxide (vi, i = O) with that of 2-methoxycinnolinium (vi, R = OMe) suggests that at high acidities the former is nitrated as its conjugate acid (vi, R = OH), but that as the acidity is lowered the free base becomes active. At high acidities 5- and 8-nitration are dominant, but as the acidity is lowered 6-nitration becomes increasingly important. The 5- and 8-nitro compounds are probably formed mainly or wholly by nitration of the conjugate acid, and the 6-nitro compound wholly or mainly from the free base. ... 

Ochiai and Okamoto showed that nitration of quinoline i-oxide in sulphuric acid at o °C gave 5- and 8-nitroquinoline i-oxides with a trace of the 4-isomer, but that at 60-100 °C 4-nitration became overwhelmingly dominant. The orientation depends not only upon temperature but also upon acidity, and kinetic studies (table 8.4 table 10.3) show that two processes are occurring the nitration of the free base (vil, R = O at C(4), favoured by low acidities and high temperatures, and the nitration of the cation (vil, R = OH), favoured by high acidities and low temperatures. ... 

---