Encounter rates

Forbes M D E 1993 The effect of n-system spacers on exchange couplings and end-to-end encounter rates in flexible biradicals J. Phys. Chem. 97 3396-400... 

NITRATION AT THE ENCOUNTER RATE IN AQUEOUS SULPHURIC AND PERCHLORIC ACIDS... 

The possibility that the rate of reaction of benzene is affected by the phenomenon of reaction at the encounter rate is a matter of importance, because benzene is the datum relative to which comparisons of reactivity are made. Up to 68 % sulphuric acid the slope of a plot of log [kffi moU s i) against — + log is unity for data relating to 25 °C, and... 

The results in table 2.6 show that the rates of reaction of compounds such as phenol and i-napthol are equal to the encounter rate. This observation is noteworthy because it shows that despite their potentially very high reactivity these compounds do not draw into reaction other electrophiles, and the nitronium ion remains solely effective. These particular instances illustrate an important general principle if by increasing the reactivity of the aromatic reactant in a substitution reaction, a plateau in rate constant for the reaction is achieved which can be identified as the rate constant for encounter of the reacting species, and if further structural modifications of the aromatic in the direction of further increasing its potential reactivity ultimately raise the rate constant above this plateau, then the incursion of a new electrophile must be admitted. 

For nitrations in sulphuric and perchloric acids an increase in the reactivity of the aromatic compound being nitrated beyond the level of about 38 times the reactivity of benzene cannot be detected. At this level, and with compounds which might be expected to surpass it, a roughly constant value of the second-order rate constant is found (table 2.6) because aromatic molecules and nitronium ions are reacting upon encounter. The encounter rate is measurable, and recognisable, because the concentration of the effective electrophile is so small. 

A similar circumstance is detectable for nitrations in organic solvents, and has been established for sulpholan, nitromethane, 7-5 % aqueous sulpholan, and 15 % aqueous nitromethane. Nitrations in the two organic solvents are, in some instances, zeroth order in the concentration of the aromatic compound (table 3.2). In these circumstances comparisons with benzene can only be made by the competitive method. In the aqueous organic solvents the reactions are first order in the concentration of the aromatic ( 3.2.3) and comparisons could be made either competitively or by directly measuring the second-order rate constants. Data are given in table 3.6, and compared there with data for nitration in perchloric and sulphuric acids (see table 2.6). Nitration at the encounter rate has been demonstrated in carbon tetrachloride, but less fully explored. ... 

Nitration at the encounter rate and nitrosation As has been seen ( 3.3), the rate of nitration by solutions of nitric acid in nitromethane or sulpholan reaches a limit for activated compounds which is about 300 times the rate for benzene imder the same conditions. Under the conditions of first-order nitration (7-5 % aqueous sulpholan) mesitylene reacts at this limiting rate, and its nitration is not subject to catalysis by nitrous acid thus, mesitylene is nitrated by nitronium ions at the encounter rate, and under these conditions is not subject to nitration via nitrosation. The significance of nitration at the encounter rate for mechanistic studies has been discussed ( 2.5). 

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. 

Under the same conditions the even more reactive compounds 1,6-dimethylnaphthalene, phenol, and wt-cresol were nitrated very rapidly by an autocatalytic process [nitrous acid being generated in the way already discussed ( 4.3.3)]. However, by adding urea to the solutions the autocatalytic reaction could be suppressed, and 1,6-dimethyl-naphthalene and phenol were found to be nitrated about 700 times faster than benzene. Again, the barrier of the encounter rate of reaction with nitronium ions was broken, and the occurrence of nitration by the special mechanism, via nitrosation, demonstrated. 

Again the uncertainty about the proportion of an observed result which is due to nitration and the proportion which is due to nitrosation exists. Thus, in expt. 11 phenol was being nitrated above the encounter rate and the observed isomer distribution could arise from a combination of nitration by whatever is the usual electrophile with nitration by a new, less reactive electrophile, or with nitrosation, or all three processes could be at work. 

If, on the other hand, the encounter pair were an oriented structure, positional selectivity could be retained for a different reason and in a different quantitative sense. Thus, a monosubstituted benzene derivative in which the substituent was sufficiently powerfully activating would react with the electrophile to give three different encounter pairs two of these would more readily proceed to the substitution products than to the starting materials, whilst the third might more readily break up than go to products. In the limit the first two would be giving substitution at the encounter rate and, in the absence of steric effects, products in the statistical ratio whilst the third would not. If we consider particular cases, there is nothing in the rather inadequate data available to discourage the view that, for example, in the cases of toluene or phenol, which in sulphuric acid are nitrated at or near the encounter rate, the... 

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. 

The limit to the significance of aromatic reactivity set by reaction at the encounter rate is reached at different levels of reactivity in different conditions. As already seen, for nitration with nitric acid in organic... 

The significance of establishing a limiting rate of reaction upon encounter for mechanistic studies has been pointed out ( 2.5). In studies of reactivity, as well as settii an absolute limit to the significance of reactivity in particular circumstances, the experimental observation of the limit has another dependent importance if further structural modification of the aromatic compound leads ultimately to the onset of reaction at a rate exceeding the observed encounter rate then a new electrophile must have become operative, and reactivities established above the encounter rate cannot properly be compared with those measured below it. 

Comparison of the observed rate of nitration with the calculated encounter rate. 

Other substituents which belong with this group have already been discussed. These include phenol, anisole and compounds related to it ( 5.3.4 the only kinetic data for anisole are for nitration at the encounter rate in sulphuric acid, and with acetyl nitrate in acetic anhydride see 2.5 and 5.3.3, respectively), and acetanilide ( 5.3.4). The cations PhSMe2+, PhSeMe2+, and PhaO+ have also been discussed ( 9.1.2). Amino groups are prevented from showing their character ( — 7 +717) in nitration because conditions enforce reaction through the protonated forms ( 9.1.2). 

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- ... 

Pyridone is one of the eompounds for which the encounter rate eriterion for... 

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... 

Any attempt to calculate partial rate factors for the i-oxides being The encounter rate criterion ( 8.2.3) is ambiguous for these compounds. 

With the oxides which are nitrated as the cations the difficulties are much less serious for the use of an acidity function is not involved. Comparison of 2,6-dimethoxy- and 3,5-dimethoxy-pyridine i-oxide with wt-dimethoxybenzene (which is nitrated at the encounter rate)... 

Reaction rates caimot be faster than coUision frequencies. Such reactions are diffiision-controUed. The encounter rate, for dmg binding to receptors is... 

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