Hydrates, of aldehydes and ketones

PRINCIPLES OF NUCLEOPHILIC ADDITION HYDRATION OF ALDEHYDES AND KETONES... 

Principles of Nucleophilic Addition Hydration of Aldehydes and Ketones... 

Hydration of aldehydes and ketones is a rapid reaction quickly reaching equilibrium but faster in acid or base than in neutral solution Thus instead of a single mechanism for hydration we 11 look at two mechanisms one for basic and the other for acidic solution... 

In the first stage of the hydrolysis mechanism water undergoes nucleophilic addi tion to the carbonyl group to form a tetrahedral intermediate This stage of the process IS analogous to the hydration of aldehydes and ketones discussed m Section 17 6... 

The hydrates of aldehydes and ketones are considerably more acidic than normal alcohols (pAl Fs 16-19). How would you account for this fact Some reported values are shown below. Explain the order of relative acidity. 

Many addition and elimination reactions, e.g., the hydration of aldehydes and ketones, and reactions catalyzed by lyases such as fumarate hydratase are strictly reversible. However, biosynthetic sequences are often nearly irreversible because of the elimination of inorganic phosphate or pyrophosphate ions. Both of these ions occur in low concentrations within cells so that the reverse reaction does not tend to take place. In decarboxylative eliminations, carbon dioxide is produced and reversal becomes unlikely because of the high stability of C02. Further irreversibility is introduced when the major product is an aromatic ring, as in the formation of phenylpyruvate. 

The reaction, by either mechanism, is fast at room temperature. However, because water is a relatively weak nucleophile, the equilibrium does not favor the product in most cases. As a result, the hydrates of aldehydes and ketones usually cannot be isolated because removal of the water solvent also drives the equilibrium back to the left. Therefore, the hydration reaction is not useful in synthesis. 

The overall reaction proceeds in two stages. The hemiacetal is formed in the hrst stage by nucleophilic addition of the alcohol to the carbonyl group. The mechanism of hemiacetal formation is exactly analogous to that of acid-catalyzed hydration of aldehydes and ketones (Section 17.6) ... 

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