Hydration and Acid-Base Catalysis

We consider first the simple addition of a nucleophile to a carbonyl carbon, preceded, accompanied, or followed by addition of a proton to the oxygen, and the reverse. The overall process (Equation 8.3) amounts to addition of H—X to C=0. The reaction differs from the additions to C=C discussed in Chapter 7 in two important respects. First, the nucleophile always becomes bonded to the 

Water adds to the carbonyl group of aldehydes and ketones to yield hydrates (Equation 8.4). For ketones and aryl aldehydes, equilibrium constants of the 

Mechanistic questions in the hydration-dehydration equilibrium center around the acid-base relationships and the precise sequence of events in the addition or elimination of the water molecule. Investigations have relied primarily on kinetics of aldehyde hydration to elucidate the mechanistic details  

We have already encountered general catalysis in Section 7.1 (p. 340). Because it is so important to the understanding of carbonyl reactions, we shall consider it here in more detail. The discussion will be restricted to aqueous solutions, because these have been the most thoroughly studied. 

The reaction rate is given by Equation 8.5. Concentration [SH+] is in turn determined by the preliminary equilibrium, for which we may write the equilib- 

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Acid—Base Catalysis. Inexpensive mineral acids, eg, H2SO4, and bases, eg, KOH, in aqueous solution are widely appHed as catalysts in industrial organic synthesis. Catalytic reactions include esterifications, hydrations, dehydrations, and condensations. Much of the technology is old and well estabhshed, and the chemistry is well understood. Reactions that are cataly2ed by acids are also typically cataly2ed by bases. In some instances, the kinetics of the reaction has a form such as the following (9) ... 

The reactions are accompanied by a considerable volume change, and a dilatometric method was employed by Bell and Higginson (1949), who added acetaldehyde-water mixtures (containing about equal quantities of MeCHO and MeCH(OH)2) to an excess of acetone, and thus measured kj, in presence of a large number of acid catalysts. The direct hydration of acetaldehyde in aqueous buffer solutions is inconveniently fast at room temperatures, but ( (j + A ) was measured dilatometrically at 0°C by Bell and Darwent (1950), who established the existence of general acid-base catalysis. 

Since rapid conversion of hemiacetal to acetal requires more acidic conditions than does formation of the hemiacetal, it is possible to measure the rate of hemiacetal production without complication from the second stage of the reaction.52 As might be expected, the hemiacetal formation displays characteristics similar to those of hydration general acid and general base catalysis are observed.53... 

Carbonyl addition reactions include hydration, reduction and oxidation, the al-dol reaction, formation of hemiacetals and acetals (ketals), cyanohydrins, imines (Schiff bases), and enamines [54]. In all these reactions, some activation of the carbonyl bond is required, despite the polar nature of the C=0 bond. A general feature in hydration and acetal formation in solution is that the reactions have a minimum rate for intermediate values of the pH, and that they are subject to general acid and general base catalysis [121-123]. There has been some discussion on how this should be interpreted mechanistically, but quantum chemical calculations have demonstrated the bifunctional catalytic activity of a chain of water molecules (also including other molecules) in formaldehyde hydration [124-128]. In this picture the idealised situation of the gas phase addition of a single water molecule to protonated formaldehyde (first step of Fig. 5) represents the extreme low pH behaviour. 

In acid-catalyzed reactions, the distinction between single-species and complex catalysis is not always clear-cut. The actual catalyst is the solvated proton, H30+ in aqueous solution, and H20 (or a molecule of the nonaqueous solvent) may thus appear as a co-product in the first step and as a co-reactant in the step reconstituting the original solvated proton, possibly also in other additional steps, e.g., if the overall reaction is hydrolysis or hydration. Moreover, the acid added as catalyst may not be completely dissociated, and its dissociation equilibrium then affects the concentration of the solvated proton. At high concentrations this is true even for fairly strong acids such as sulfuric, particularly in solvents less polar than water. Such cases are better described as acid-base catalysis (see Section 8.2.1). 

Several examples in previous sections fall under the heading of acid-base catalysis. Nitration of aromatics with catalyst acid HB and its conjugate base B is one of these (see reaction 4.6 in Section 4.1). Also, acid-catalyzed hydrolysis and hydration reactions such as 8.3 and 8.7 can be viewed as belonging to this category because the original catalyst actually is H30+ rather than H+ and is reconstituted in a step that involves its conjugate base, H20, as co-reactant. 

The potential for general acid/base catalysis is constrained by the available functional groups that can participate in proton transfer. The pKas of RNA nucleobases are 3.5 and 4.2 for A and C, and 9.2 for G and U and the ribose 2 OH has a pKa of 12 (Fig. 2a). As outlined below, metal ions can be bound tightly by RNA and such hydrated Mg(2- -) ions have pKa of 10. Thus, at neutral pH, A and C would be good acids, but at a low concentration relative to the unprotonated form. Although G and U could serve as bases, they exist predominantly in their protonated forms. Conversely, A and C could act as bases... 

The most important t5q)es of homogeneous catalysis in water are performed by acids, bases and trace metals. A wide variety of mechanisms have been outlined for acid/base catalysis and are presented in kinetics texts (e.g. Moore and Pearson, 1981 Laidler, 1965). A number of bases have been observed to catalyze the hydration of carbon dioxide (Moore and Pearson, 1981 Dennard and Williams, 1966). Examples are listed in Table 9.7 for OH and the base Co(NH3)gOH2. The most dramatic effect is the catalysis of HS-oxidation by cobalt-4,4, 4",4"-tetrasulfophthalocyanine (Co-TSP ). At concentrations of 0.1 nM Co-TSP the reaction rate was catalyzed from a mean life of roughly 50 h to about 5 min. The investigators attributed the reason for historically inconsistent experimentally determined reaction rates for the H2S-O2 system by different researchers partly to contamination by metals. Clearly, catalysis by metal concentrations that are present in less than nanomolar concentrations is likely to be effective in aquatic systems. We shall see that similar arguments apply to catalysis by surfaces and enzymes. 

Many industrial processes are based on acid/base catalysis (over 130). Examples include alkylation, etherification, cracking, dehydration, condensation, hydration, oligomerizations, esterification, isomerization and disproportionation. The dimensions of the processes range from very large scale in the field of refinery (thousand tons per day) to very small productions in fine and specialty chemical industries. In the latter case, adds and bases are often used in stoichiometric quantities, leading thus to large amounts of waste. 

Photfrfysis of a-Diazo Carbonyl Compounds - Some recent advances in the matrix photochemistry of diazoketones, including some heterocyclic species, have been reviewed. Flash photolysis of 10-diazo-9(10//)-phenanthrenone (35) in aqueous solution led to the detection of two transient species on the pathway to the final product, fluorene-9-carboxylic acid. These were identified, from solvent isotope effects and the nature of the observed acid-base catalysis, as fluorenylideneketene (36, X = CO) and the enol of fluorene-9-carboxylic acid (36, X = C(0H)2), formed by hydration of the ketene. In related studies, fluorenylideneketene was found to react with amines to give ylides as intermediates on the route to the amide final products. The product distribution from the photochemical reactions of 2-diazo-3-oxo-5,10,15,20-tetraphenylchlorins with alcohols strongly depends on the central metal ion of the irradiated diazoketones. ... 

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... 

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