Acid-base catalysis, salt effects

The rate of a reaction that shows specific acid (or base, or acid-base) catalysis does not depend on the buffer chosen to adjust the pH. Of course, an inert salt must be used to maintain constant ionic strength so that kinetic salt effects do not distort the pH profile. 

One can test for general acid-base catalysis by varying [BH+] and [B] at constant pH. An easy test is to dilute the buffer progressively at a constant ratio of [BH+]/[B], making up any ionic strength change so as not to introduce a salt effect. If the rate is invariant with this procedure, then general acid-base catalysis is absent under the circumstances chosen. 

The mutarotation constant, ki + ko is the sum of the constants for the two opposing reactions, and k lki is the equilibrium constant. Lowry and Hudson pointed out and showed that the same value is obtained for ki + kj from the mutarotation of the a and /8 anomers, a situation which has been experimentally confirmed by many others. Hudson found the reaction constant to be independent of the concentration of sugar over a wide range, and dependent on catalysis by both acids and bases, as had also been shown less precisely by Urech and by Levy. The effect of acids, bases, and salts will be considered in more detail in Part II of this review. 

A similar substitution on anilines causes the reverse effect. Nitro groups in ortho position either in the isocyanate or the aniline lower the reactivity by steric hindrance. These authors also reported that the reaction is subject to catalysis by pyridine, tertiary bases, and certain carboxylic acids but is unaffected by water, inorganic acids, bases, or salts. Relative rates for the reactions of some primary aliphatic amines with phenyl isocyanates have been determined by Davis and Ebersole (52). 

II. The Empirical Laws of Acid-Base Catalysis 1. Salt Effects... 

The subject of salt effects in one which arises in all reaction-kinetic problems involving electrolytes and has no special relevance to acid-base catalysis. However, much of the early work on salt effects was in fact carried out with catalyzed reactions, and a neglect of these effects is still the commonest cause of misinterpretation of data on acid-base catalysis, so that a brief account will be given here. It is convenient to include under the heading of salt effects the various ways in which the assumptions of the classical theory have been modified by modern views on electrolytic solutions. Since the catalyst itself is commonly ionic, the same problems often arise even when no other electrolyte has been added to the system. 

The -primary salt effect deals with the effect of salt concentration on reaction velocity when the reacting system involves no equilibria which can be displaced by a change in ionic environment. This effect can be very large when both the reacting species are ions, but it is of less importance in acid-base catalysis, where the substrate is almost always an uncharged molecule. To avoid complications due to secondary salt effects, the primary effect is best studied in catalysis by solutions of strong acids and bases, and there exists a large body of experimental data. Some of the main conclusions are as follows ... 

General acid-base catalysis is not involved since the addition of other salts had no effect on the reaction rates. The [Cr(LL)2F(0H2)](C104)2 complexes with LL = 1,3-pn, bipy, or phen were isolated. ... 

The above discussion shows that the dependence of the reaction rate upon the pH contains very important information on the reaction mechanism. Each rate must be measured at constant pH, which usually involves measuring it in a buffer solution. In addition, usually an inert salt is added to maintain ionic strength constant to avoid the salt effects discussed in Chapter 9. In fact, experimentally, the rates are measured at different buffer concentrations, keeping the pH and the ionic strength constant. Under these conditions, and for a constant substrate concentration, there is a linear dependence between the rate and the buffer concentration, as illustrated in Figure 13.3. Extrapolating to zero buffer concentration, one obtains the rate for a constant pH. When general acid-base catalysis is present. 

In acid-base catalysis it is convenient to distinguish between a primary salt effect and a secondary salt effect. The primary effect is related to the dependence of the rate constant on the activity coefficients of the species entering the rate law... 

In this solvent the reaction is catalyzed by small amounts of trimethyl-amine and especially pyridine (cf. 9). The same effect occurs in the reaction of iV -methylaniline with 2-iV -methylanilino-4,6-dichloro-s-triazine. In benzene solution, the amine hydrochloride is so insoluble that the reaction could be followed by recovery. of the salt. However, this precluded study mider Bitter and Zollinger s conditions of catalysis by strong mineral acids in the sense of Banks (acid-base pre-equilibrium in solution). Instead, a new catalytic effect was revealed when the influence of organic acids was tested. This was assumed to depend on the bifunctional character of these catalysts, which act as both a proton donor and an acceptor in the transition state. In striking agreement with this conclusion, a-pyridone is very reactive and o-nitrophenol is not. Furthermore, since neither y-pyridone nor -nitrophenol are active, the structure of the catalyst must meet the conformational requirements for a cyclic transition state. Probably a concerted process involving structure 10 in the rate-determining step... 

In the case of A -alkyl amino acids, the oxazohum ion 18 is formed even in the absence of base catalysis because of the electron-donating effect of the A -alkyl group,thus increasing the risk of racemization (Scheme 8). Although proline can be considered as an N-alkylated amino acid, formation of the oxazolium salt is not observed, probably as a consequence of the steric constraints of the five-membered ring which disfavors cyclization.P l As a result, in... 

Naegeli et al. [177] reported mild catalysis by tertiary amines and carboxylic acids, but not by water, inorganic acids, salts or bases. In contrast. Craven [179] found that the typical tertiary amines and acids had little catalytic effect in the systems he studied. Certain substituted ureas appeared to catalyse the reaction to a greater extent than many tertiary amines. Ten mole % of butyric acid reduced the half-life of the reaction between phenyl isocyanate and o-toluidine by 57%, and 10 mole % of N-phenyl-N -o-tolylurea reduced it by 38%. Arnold et Jil. [178] and... 

The classical theory of catalysis supposed that the hydrogen and hydroxyl ions were the only effective catalysts in solutions of acids and bases. In a few instances early attempts were made to remedy some of the discrepancies encountered by attributing some catalytic power to undissociated acid molecules, but these attempts were mostly based on incorrect values for degrees of dissociation, and they did not take into account the possibility of primary or secondary salt effects. However, later work has shown definitely that species other than hydrogen and hydroxyl ions often can exert a catalytic effect, and the development of these ideas was closely linked with a closer understanding of the nature of the hydrogen ion in solution, and with the clarification of acid-base definitions (cf. Bell, 11). 

These researchers have used supercritical CO2 to tune reaction equilibria and rates, improve selectivity, and eliminate waste. They were the first to use supercritical CO2 with phase transfer catalysts to separate products cleanly and economically. Their method allows them to recycle their catalysts effectively. They have demonstrated the feasibility of a variety of phase transfer catalysts on reactions of importance in the chemical and pharmaceutical industries, including chiral syntheses. They have carried out a wide variety of synthetic reactions in near-critical water, replacing conventional organic solvents. This includes acid- and base-catalysis using the enhanced dissociation of near-critical water, negating the need for any added acid or base, and eliminating subsequent neutralization and salt disposal. They have used CO2 to expand organic fluids to make it easier to recycle... 

---