Hydration of ketones

Hydration (Section 17.6) Can be either acid- or base-catalyzed. Equilibrium constant is normally unfavorable for hydration of ketones unless R, R, or both are strongly electron-withdrawing. 

In the case of the bis phosphine derivatives of the group 7b metals, the lability of the oxygen atoms was so markedly retarded by substitution that it was necessary to enhance their reactivity by means of base catalysis (15, 14), a process having mechanistic features common wi Tx general base catalysis of the hydration of ketones (eq. 6) (15). 

In later discussion on the correlation of entropies of activation and reaction mechanism, we shall be particularly concerned with reactions in aqueous solution. Particularly germane in this respect is a recent study by Bell and McDougall (1960) on the hydration of ketones and aldehydes (Table 6). The reaction,... 

We showed in Figs. 3-2 and 3-3 that the tetrahedral intermediate which is initially formed from the reaction of a nucleophile with a carbonyl compound may further react in a number of different ways. In this section, we will consider some reactions which proceed along the pathway indicated in Fig. 3-3. The hydration of ketones is a reaction analogous to the hydrolysis of an ester, with the first step of the reaction involving nucleophilic attack of water on the carbonyl group. The tetrahedral intermediate is trapped by reaction with a proton to yield the hydrated form of the ketone, the geminal diol (Fig. 3-15). Similar reactions occur with alcohols as nucleophiles to yield, initially, hemiacetals. 

Mechanism 18-2 The Wittig Reaction 844 18-13 Hydration of Ketones and Aldehydes 847... 

These stability effects are apparent in the equilibrium constants for hydration of ketones and aldehydes. Ketones have values of Keq of about 10-4 to 10-2. For most aldehydes, the equilibrium constant for hydration is close to 1. Formaldehyde, with no alkyl groups bonded to the carbonyl carbon, has a hydration equilibrium constant of about 40. Strongly electron-withdrawing substituents on the alkyl group of a ketone or aldehyde also destabilize the carbonyl group and favor the hydrate. Chloral (trichloroacetaldehyde) has an electron-withdrawing trichloromethyl group that favors the hydrate. Chloral forms a stable, crystalline hydrate that became famous in the movies as knockout drops or a Mickey Finn. 

In accordance with the above discussion, general base catalysis is not found in thiol addition reactions to aldehydes and ketones only specific base catalysis is prevalent (Lienhard and Jencks, 1966). This is in contrast to the general base-catalyzed hydration of ketones or aldehydes. The reactions of the carbonyl group at the carboxylic acid level of oxidation have much in common with the reactions of the carbonyl group at the aldehyde or ketone level of oxidation. In an excellent review on simple carbonyl addition reactions Jencks (1964) has discussed in detail the mechanisms of catalyzed additions to the carbonyl group of ketones and aldehydes. For general base-catalj ed additions the mechanism... 

Hydrates of ketones and aldehydes are also known and, in general, as already noted in Chapter 5, they too are unstable with regard to the carbonyl compound. Exceptions occur when there are electron-withdrawing substituents on the adjacent carbon (aldehydes) or carbons (ketones) and, as shown by the large equilibrium constant, some of the hydrates can be isolated (Figure 8.4). 

FIGURE 19.74 In the hydration of ketones, the hydrate is usually not favored at equilibrium. Similarly, in the aldol reaction of ketones the initial product molecule is not usually favored, but the dehydrated product is. 

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