Kinetically equivalent mechanisms

It is absolutely imperative to be aware that more than one mechanism may fit the experimental observations and the observed kinetics, and that an exact fit of prediction with experiment does not prove a given mechanism to be the correct one. 

This is one of the fundamental tenets of the scientific method, viz., that it is not possible to prove a hypothesis using experimental data, whereas it is possible to refute a hypothesis by reference to experimental data. All that can be said is that the data fits a given hypothesis, so that the hypothesis is a plausible one. The possibility remains open that, in the future, experimental evidence may show that the hypothesis is not justified. 

Question. The reaction between nitric oxide (nitrogen monoxide) and oxygen gives nitrogen dioxide according to the stoichiometric equation. 

This reaction is second order in NO and first order in 02. The following mechanisms can be proposed. 

Assuming the steady state approximation, deduce the rate expressions for each mechanism. 

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The mechanisms available to intramolecular reactions are the same as those of intermolecular reactions. The same problems of kinetic equivalence of rate terms may arise, and Table 6-3 shows some kinetically equivalent mechanisms for intramolecular reactions of the acyl function. The efficiency of intramolecular reactivity may be difficult to assess. One technique, described above as a method for the detection of an intramolecular reaction, is to make a comparison with an analog incapable of the intramolecular process. Thus p-nitrophenyl 5-nitrosalicylate, 17, hydrolyzes about 2500 times faster than p-nitrophenyl 2-methoxy-5-nitrobenzoate, 18. 

In principle, reactions which are subject to electrophilic catalysis by protons can be catalysed by metal ions also (e.g. Tee and Iyengar, 1988 Suh, 1992). However, metal ions may function in other ways, such as to deliver a hydroxide ion nucleophile to the reaction centre (e.g. Dugas, 1989 Chin, 1991), and it is often difficult to decide between kinetically equivalent mechanisms without resorting to extensive (and intensive) model studies. Use of the Kurz approach may help to resolve such ambiguities, as shown below. 

Even in this case, traditionally, a logarithmic form is used [Equation (9)] to treat kinetic data. The intercept of the linear plot (Figure 3) gives the value of k0 and the slope the value of ZAZB, and this is very useful information for ionic reactions to discriminate between kinetically equivalent mechanisms ... 

Finally, different mechanisms must obtain in those cases where the breakdown of the tetrahedral intermediate is the slow step of the reaction. Two kinetically equivalent mechanisms are possible in this case also. Here, too, the catalyst may be involved as a general base, in which circumstances it would catalyze the elimination of the leaving group by the E-2 mechanism, viz-... 

The only time that kinetically equivalent mechanisms can be distinguished is when one of the mechanisms involves an impossible step and generates, say, a... 

In examples such as the above, the rate law establishes the composition of the activated complex (transition structure), but not its structure, i.e. not the atom connectivity, and provides no information about the sequence of events leading to its formation. Thus, the rate law of Equation 1.2 (if observed) for the reaction of Equation 1.1 tells us that the activated complex comprises the atoms of one molecule each of B and X, plus a proton and an indeterminate number of solvent (water) molecules, but it says nothing about how the atoms are bonded together. For example, if B and X both have basic and electrophilic sites, another mechanistic possibility includes a pre-equilibrium proton transfer from AH to B followed by the reaction between HB+ and X, and this also leads to the rate law of Equation 1.2. Observation of this rate law, therefore, allows transition structures in which the proton is bonded to a basic site in either B or X, and distinguishing between the kinetically equivalent mechanisms requires evidence additional to the rate law. 

We have already seen from Equation 4.11 that it is not possible to distinguish between the first four reactions of Scheme 4.6 from kinetic data at constant pH. But when the influence of acidity is taken into account, only two possibilities are compatible with the observed rate law - the first and the fourth (r3 and 7-4). These two are kinetically equivalent mechanisms, i.e. they cannot be distinguished from the form of the rate law alone - the distinction has to be made on other grounds. 

Table 4.3 Two kinetically equivalent mechanisms for the chlorination of amines by aqueous chlorine at pH > 5.

Note. The constitution of the activated complex is the same in both cases again a feature of kinetically equivalent mechanisms. 

This is an anion-catalysed mechanism analogous to metal ion or cation-catalysed reactions. But the kinetically equivalent mechanism of general acid hydrolysis by HSO4, analogous to general base hydrolysis, is also possible (Section 8.1.3 and Problem 8.3). 

Reaction of NO(g) with 02(g) - analysis and demonstration of kinetically equivalent mechanisms, 198-201... 

Base hydrolysis of an ester in presence of metal ions, metal ion catalysis - analysis in terms of kinetically equivalent mechanisms, 330-331 Acid hydrolysis of a charged ester in the presence of SC>4 (aq) anion catalysis - analysis in terms of kinetically equivalent mechanisms, 332-336 Decarboxylation of /3-ketomonocarboxylic acids - formulation of the rate expression from the mechanism, 339-341... 

At pHs above the p/STg of the 3-carboxyl group, the rate of degradation of penicillin is acid catalysed up to about pH 6. The pathway for hydrolysis could be an acid catalysed reaction of the penicillin with an ionised carboxylate or the kinetically equivalent mechanism, the spontaneous degradation of penicillin with an unionised carboxyl function as indicated in (3). 

Zinc(II) and tris-buffers are effective catalysts for the aminolysis of benzylpenicillin. It is suggested that this is due to formation of a ternary complex in which the metal ion binds both penicillin and tris. Nucleophilic attack of the ionised hydroxyl on bound tris forms a penicilloyl ester which may then react with tris to form a penicilloyl amide (Schwartz, 1982 Tomida and Schwartz, 1983). A kinetically equivalent mechanism, however, would simply involve nucleophilic attack of tris on the zinc-penicillin complex. 

As with intermoleculariy general-acid and general-base catalysed reactions, it is frequently difficult to distinguish between kinetically equivalent mechanisms and eliminate all but one. Mechanisms which involve intramolecular nucleophilic catalysis are often kinetically equivalent to those which involve intramolecular general-acid or base catalysis. As these do not involve a proton transfer they will not be discussed in this chapter unless the evidence is fairly evenly balanced between them and the latter. 

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