Reactions Catalyzed by Acids and Bases

One approach to the mechanism of a reaction is by way of kinetic studies. Kinetic experiments yield the order of a reaction. For example, if A and B react and the rate equation is 

Pedersen (39) has presented the theory of protolytic reactions and considers that the mechanisms are usually bimolecular. He makes the seemingly justifiable assumption that a proton cannot move spontaneously from one place in the molecule to another without a catalyst, while valency electrons can move spontaneously within the molecule. For example, in the triad systems, 

It can be shown that the mechanism expressed in equation (41) always appears as a first-order reaction catalyzed by bases (proton acceptors) in general, when the hydrogen ion concentration is so great that [RH] [ ]. If 1 takes up protons to form mainly SH, we measure the velocity of the protolytic reaction between RH and B, i.e., the velocity of dissociation of the very weak acid RH. If I takes up protons to form RH, the apparent basic catalysis is a disguised acid catalysis of the ion I. If neither of these possibilities is especially favored, we get an apparent basic catalysis which is the result of both a protolytic reaction between RH and the bases and between the acids and I. From the kinetic experiments, it is impossible to decide which of the three possible cases we have in a given reaction. 

For general acid catalysis the mechanism is expressed by the scheme 

A part of the evidence for the mechanisms given in equations (40) and (42) is provided by the work of Lowry and co-workers (Lowry and Richards, 113 Lowry and Faulkner, 24) on the mutarotation of tetra methylglucose. In water the reaction proceeds at a measurable rate, and it is clearly catalyzed by both acids and bases. In aqueous solution pyridine is a powerful catalyst but in pure dry pyridine no reaction occurs, and likewise in pure dry re-cresol there is no reaction. Upon investigating the reaction in a mixture of pyridine and n-cresol, Lowry and Faulkner (24) found it to take place very rapidly. From these experiments Lowry drew the important conclusion that a proton cannot by itself wander from one part of the molecule to another. The transformation can occur only if the medium in which the molecule is placed has both acidic and basic properties, so that a proton can be removed from the molecule at one place and a proton added to the molecule at another place. Now these experiments furnish strong support to the mechanism of reactions (40) and (42) whereby both members of the conjugate acid-base pair play a part in the reaction. Instead of representing this mutual dependence by means of consecutive bimolecular reactions, Lowry chose to represent it by means of one trimolecular reaction 

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In conclusion it should be pointed out that the ternary picture cannot be dismissed merely on the grounds that a triple collision is an improbable event. Exactly the same result is achieved kinetically if two of the molecules concerned associate together loosely (e.g., by hydrogen bonding) before the approach of the third. Although the modem tendency is to split up complex reactions into consecutive bimolecular steps (Hinshel-wood, 122) there appear to be cases in which this cannot be done (Bell and Darwent, 61), and the ternary hypothesis must certainly be considered as one of the possible mechanisms for reactions catalyzed by acids and bases. 

The study of catalysis by acids and bases played a very important part in the development of chemical kinetics, since many of the reactions studied in the early days of the subject were of this type. The early investigations of the kinetics of reactions catalyzed by acids and bases were carried out at the same time that,the electrolytic dissociation theory was being developed, and the kinetic studies contributed considerably to the development of that theory. The reactions considered from this, point of view were chiefly the inversion of cane sugar and the hydrolysis of esters. 

The intermediate X is now an addition compound formed from C and S, and in the second step it forms products. This scheme also applies to many reactions catalyzed by enzymes. For reactions catalyzed by acids and bases, however, it is necessary to include the additional species Y, W, and Z. 

Synthesis of Biodiesel Reactions Catalyzed by Acids and Bases. 

In a study of the acid-catalyzed formation of the hemiacetal, Grunwald has shown that the data best fit a mechanism in which the three steps shown here are actually all concerted that is, the reaction is simultaneously catalyzed by acid and base, with water acting as the base ... 

Bronsted and Guggenheim [J. /Am. Chem. Soc., 49 (2554), 1927] have studied the mutaro-tation of glucose as catalyzed by acids and bases. The reaction takes place slowly in pure water, is weakly catalyzed by hydrogen ions, and is strongly catalyzed by hydroxide ions. When strong acids and bases are employed as catalysts, the apparent first-order rate constants can be written as... 

Aldonamides are readily prepared by reaction of lactones with liquid ammonia (86,99,100), with ammonium hydroxide (101,102), or by bubbling ammonia gas into alcoholic solutions of the sugar lactones (103-104). Aldonamides of the tetronic adds are stable in aqueous solution (105), but penton- or hexon-amides are hydrolyzed, as shown by the change of the optical rotation of the amide solutions (106). The hydrolysis is catalyzed by acids and bases, and the product was the ammonium salt of the aldonic acid. 

This hypothesis was supported in 1974 when he and others [10] reported that the reaction can be simultaneously catalyzed by acids and bases. The methanolysis of aryloxysilanes was carried out in sodium formate-formic acid buffers. The rate law developed showed a first-order dependence on both the base and the acid. This led to the proposal of a concerted-displacement mechanism ... 

The electrophilic aromatic substitution reaction may be advantageously modeled by isotopic exchange reactions. Shatenshtein and his co-workers77-79 studied hydrogen exchange catalyzed by acids and bases in nonaqueous solution, and their studies throw considerable light on both electrophilic substitution and protophilic (base-induced) replacement of hydrogen in the system (see Section V, A). 

The reaction of carbodiimides with water to give the corresponding N,N -disubstituted ureas 433 is catalyzed by acids and bases. For example, acetic acid is an effective catalyst in the formation of ureas from sugar derived carbodiimides. ... 

These catalysts increase the rate of the reaction, but they do not affect the equilibrium constant. Starting materials that give a low yield of gcm-diol do so whether or not a catalyst is present. Because these reactions are reversible, the conversion of gem-diols to aldehydes and ketones is also catalyzed by acid and base, and the steps of the mechanism are reversed. 

The hydrocyanation of aldehydes provides access to synthetically important a-hydroxy carboxylic acids. This reaction can be catalyzed by acids and bases, but acid catalysis is more suitable because the presence of a base leads to racemization of cyanohydrins. 

These experiments employing acidic media were at best only semi-quantitative, and none comprised a systematic investigation of the catalysis. Nevertheless, they placed the transformation in a new light and broadened the opportunities for investigating its mechanism. From the dependence of the reactions on the concentrations of formate, acetate, or succinate ions, Ashmarin argued for a general add and base catalysis. The results of Petuely s experiments implied the same kind of catalytic effect, and Petuely wrote the reaction as an enolization catalyzed by acids and bases. 

Nitrile hydrolysis is known to be catalyzed by acids and bases. None were added in the study whose Delplots are shown here. However, butyric acid is formed and must be assumed to accelerate the reaction autocatalytically. This suggest a network with a catalytic reaction parallel to the first thermal step ... 

The term v0 represents what is commonly described as the spontaneous reaction, though this is really a misnomer, since it is actually due to catalysis by solvent molecules, acting as acids or bases. It appears that all reactions catalyzed by acids or bases can be arrested completely in solvents having no acidic or basic properties (e.g., hydrocarbons), and an apparently uncatalyzed reaction of this type can usually be traced to the presence of some adventitious acidic or basic catalyst. 

If it is accepted that reactions catalyzed by acids or bases involve at some stage a slow acid-base reaction, then the Bronsted relation (cf. Sec. II.4) assumes a reasonable aspect. The constants used to express the strengths of the catalyzing species are usually defined with reference to an equilibrium with some standard acid-base system such as the solvent, but they could in principle be defined in terms of the (hypothetical) protolytic equilibrium between the catalyst and the substrate. The Bronsted relation then amounts to a parallelism between the rates and equilibrium constants of a series of similar reactions. The general form of the relation can in fact be inferred without any reference to a molecular interpretation. Suppose that we have any acid-base equilibrium... 

Work of this kind has been done for nonenzymic reactions, such as the hydrolyses of esters catalyzed by acids and bases. In most cases the labeled oxygen atom is found in the resulting alcohol, and not in the acid, indicating that there is breaking of the bond between the oxygen atom and the carbonyl group ... 

The nature of catalysis in homogeneous systems has been the subject of a considerable amount of research. A catalyst is any substance which affects the rate of reaction but is not consumed in the overall reaction. From thermodynamic principles we know that the equilibrium constant for the overall reaction must be independent of the mechanism, so that a catalyst for the forward reaction must also be one for the reverse reaction. In aqueous solution, a large number of reactions are catalyzed by acids and bases for our purposes we shall employ the Bronsted definition of acids and bases as proton donors and acceptors, respectively. Catalysis by acids and bases involves proton transfer either to or from the substrate. For example, the dehydration of acetaldehyde hydrate is subject to acid catalysis [20], probably by the mechanism (II). 

When applied to reactions catalyzed by acids or bases, the Bronsted relationship has a slightly different connotation. Examples of these are the base-catalyzed halogenation of ketones and esters and the acid-catalyzed dehydration of acetaldehyde hydrate. For an acid-catalyzed reaction. 

So far, the Polanyi relation has been applied only to catalytic sequences with free radicals as intermediates. But its scope is much wider. Many organic reactions in the liquid phase proceed through ionic intermediates and arc catalyzed by acids and bases. Before the Polanyi relation is shown to correlate rate constants in acid-base catalysis, it will be put in an equivalent form by a series of self-explanatory steps. The temperature is assumed to be constant. 

Substances whose reactions undergo homogeneous catalysis are commonly known as substrates. There are several different types of homogeneous catalysis. Examples in the gas phase sometimes involve chain mechanisms. Reactions in solution are commonly catalyzed by acids and bases, and many reactions in biological systems are catalyzed by enzymes, which are proteins. Reactions in aqueous solution are often catalyzed by ions of variable valency. 

Sometimes when reactions are catalyzed by acids and bases there is little sign of any effect other than catalysis by hydrated hydrogen ions (usually written as H30" ) or by hydroxide ions. One then speaks of specific acid-base catalysis, and the rate of reaction might be of the form... 

The activation energy for stereoisomerization of metal carbonyl hydrides varies considerably. Complexes possessing the coordination numbers 6 and 4 are generally inert, while compounds which have coordination numbers 5 or higher than 6 are usually stereochemically labile. Because of crucial importance in catalytic processes, the isotopic H-D exchange between hydrido complexes and hydroxyl solvents, deuterium, and olefins is of particular interest. Often, exchange reactions with solvents such as D2O or EtOD are catalyzed by acids and bases. 

The reaction, or hydration, of PO with water to produce PG is utilized commercially. Some dipropylene glycol, tripropylene glycol, and higher-order PGs are also produced. As the molar ratio of PO to water is increased, the proportion of higher-molecular-weight glycols in the product is increased. Usually, about 15-20 mol water per mole epoxide is used in the production of PG. The reaction is catalyzed by acids and bases however, in the commercial processes, heat and pressure are applied without catalyst. 

A gem-diol is commonly referred to as the hydrate of the corresponding aldehyde or ketone. These compounds are unstable and are rarely isolated. This reaction is catalyzed by acids and bases. The mechanism is identical to that for the addition of alcohols, which is discussed next. 

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