6.2.2 Reactions of Aldehydes and Ketones
The nucleophilic addition to the carbonyl group is the most important reaction of aldehydes and ketones. Several nucleophiles such as water, alcohols, cyanide etc attack the carbonyl carbon. But, it should be noted that all adducts of this addition reaction are not stable and many reaction are readily reversible. The reaction can be catalyzed by the presence of both acids and bases. The mechanisms are given below.
Since in both cases, the amount of negative charge increases in transition state, so it is expected that electron withdrawing substituents in the carbonyl compound will enhance the rate of reaction.
6.2.2.1 Hydration
The addition of water to aldehydes and ketones seems insignificant as the reaction is usually reversible with the equilibrium lying largely to the left. However, in some cases the hydrate may be stabilized due to various reasons. Thus, powerful electron withdrawing effect on the carbonyl carbon may facilitate hydration thereby moving the equilibrium to the right. Thus, trichloroethanal, diphenylpropantrione and ninhydrin readily form their corresponding hydrates (Scheme 9). Further stabilization is also provided by the hydrogen bonding interactions.
Scheme 9
6.2.2.2 Acetal Formation
The reactions of aldehydes with one equiv of alcohols yield hemiacetals. The reaction follows the same pattern as with hydration and stable hemiacetals can be isolated by using aldehydes possessing electron withdrawing groups.
Hemiacetals may react with one more equiv of alcohol to form acetals. The reaction requires specific acid catalysis indicating that the loss of water as the slow rate determining step.
This reaction is not very feasible with ketones however, ketones do react with 1,2-diols to form cyclic acetals (Scheme 10). The fact that the reaction can be made to go with 1,2-diols but not with simple alcohols (ROH) is due to the entropy factor for the former being more favourable than that for the latter, which involves a decrease in the number of molecules on going from starting material to product. The acetals are not susceptible to hydrolysis by a base and thus are used as a protecting group.
Scheme 10
6.2.2.2 Cyanohydrin Synthesis
The addition of cyanide leads to the formation of cyanohydrins, a class of molecules with interesting synthetic application. The formation of cyanohydrin is also a reversible reaction and the equilibrium can be shifted to the right by using an acid or base as catalyst. In this case the rate limiting step is the attack of the nucleophile. This reaction proceeds quantitatively for aldehydes and simple ketones but not so for aryl alkyl ketones and diaryl ketones (Scheme 11).
Scheme 11
As told above the cyanohydrin moiety is of synthetic importance and it can be easily transformed into other important functionalities. Thus, the OH group can undergo several functional group transformations such as oxidation and dehydration. Similarly, the cyano group can be reduced to amines or oxidized to carboxylic acids.
