Carboxylic Acids and Derivatives
Carboxylic acid derivatives generally undergo substitution reactions instead of addition reactions like aldehydes and ketones. The reactivity of carboxylic acid derivatives can be explained by the relative stability of the leaving groups. Since Cl-1 is a stable ion, acid chlorides are very reactive. However, NH2-1 is a very strong base, and so amides are relatively stable (unreactive). The relative stability of these derivatives is shown in the table below.
| Most Reactive | Acid Chloride |
¬¾(Addition of SOCl2)¾ | |||
| ¯ |
Anhydride |
||||
| ¾(Addition of ROH)® ¾(Addition of H2O)® |
Ester |
Carboxylic Acid |
¬(Hot acid)¾ ¬(Hot base)¾ |
||
| Least Reactive | ¾(Formed by addition of amine)¾® | Amide |
|||
In general, reactions proceed relatively easily going from a more reactive compound to a less reactive compound. For example, addition of alcohol to an acid chloride gives an ester. The reverse reactions are generally more difficult. The most important of these reverse reactions is the hydrolysis of amides, which requires high temperatures, an aqueous solvent, and a strong acid or strong base as a catalyst.
Synthesis of acid chlorides is done most conveniently by addition of thionyl chloride (SOCl2) to a carboxylic acid.
Claisen Condensation
The Claisen condensation is almost identical to the aldol condensation. In the first step, a strong base abstracts the proton (H) from an a-carbon, generating a carbanion, which is a good nucleophile. In the second step, this carbanion attacks a second molecule containing a carbonyl. In the aldol condensation, the resulting anion is protonated to leave an alcohol. In the Claisen condensation, an alkoxide group is lost to regenerate a ketone.
