Carboxylic acid derivatives are very reactive. The following sections detail how the various carboxylic acid derivatives can be converted one into another.
Reactions of acid halides (acyl halides). Acyl halides are very reactive and easily converted to esters, anhydrides, amides, N‐substituted amides, and carboxylic acids. In the following reactions, X represents any halide.
An acid halide can be converted to an ester by an acid catalyzed reaction with an alcohol.
An anhydride may be produced by reacting an acid halide with the sodium salt of a carboxylic acid.
Reacting ammonia with an acid halide produces an amide.
Reacting a primary amine with an acid halide creates an N‐substituted amide.
Similarly, reacting a secondary amine with an acid halide produces an N,N‐disubstituted amide.
Finally, hydrolysis of an acid halide with dilute aqueous acid produces a carboxylic acid.
Reaction of anhydrides. Anhydrides react rapidly to form esters, amides, N‐substituted amides, and carboxylic acids.
Reaction of an alcohol with an anhydride creates an ester and a carboxylic acid.
Reacting an anhydride with ammonia produces an amide and a carboxylic acid salt.
A primary amine reacts with an anhydride to give an N‐substituted amide.
Similarly, a secondary N‐substituted amine reacts with an anhydride to produce an N,N‐disubstituted amide plus a carboxylic acid salt.
Finally, reacting an N,N‐disubstituted amide anhydride with dilute aqueous acid produces a carboxylic acid.
Reactivity of carboxylic acid derivatives
The conversion of one type of derivative into another occurs via nucleophilic acyl substitution reactions. In these types of reactions, any factor that makes the carbonyl group more easily attacked by a nucleophile favors the reaction. The two most important factors are steric hindrance and electronic factors.
Sterically unhindered, accessible carbonyl groups react more rapidly with nucleophiles than do hindered carbonyl groups. Electronically, groups which help polarize the carbonyl group make the compound more reactive. Thus acid chlorides would be more reactive than esters, because the chlorine atom is much more electronegative than an alkoxide ion.
Based on the above factors, the order of reactivity of carboxylic acid derivatives is
The more reactive acid derivative can be easily converted into a less reactive derivative. However, the opposite cannot occur. Thus, less reactive derivatives cannot be converted into their more reactive cousins.
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