Question

Which of the following will most easily react with an amine to form an amide? A. acyl chloride B. ester C. carboxylic acid D. acid anhydride

Short answer

Acyl chloride

Step-by-step solution

Understand the Reaction

An amine reacts with a carboxylic acid derivative to form an amide. The reactivity of the carboxylic acid derivative determines how easily the reaction occurs.

Compare Reactivities

Among the given options, compare the reactivity of acyl chloride, ester, carboxylic acid, and acid anhydride with amines. Usually, acyl chlorides are the most reactive towards nucleophiles, including amines.

Determine the Most Reactive Derivative

Acyl chloride is the most reactive among the given options because it has a good leaving group (chloride ion), which makes it more susceptible to nucleophilic attack by the amine, forming an amide.

Key concepts

Carboxylic Acid Derivatives

Carboxylic acid derivatives are compounds that can be hydrolyzed to carboxylic acids. They include a variety of functional groups that differ mainly by the nature of the leaving group. The major derivatives are:

• Acyl chlorides
• Esters
• Amides
• Anhydrides

Because of their structural differences, these derivatives have different levels of reactivity.
The reactivity mainly depends on how easily the leaving group can depart. Now, let's dive into each derivative's specifics and their reactivity.

Amine Reactivity

Amines are nucleophiles, meaning they donate a pair of electrons to form a new bond. In reactions with carboxylic acid derivatives, amines attack the carbonyl carbon because it is electrophilic.
The reactivity of amines depends on the type of carboxylic acid derivative they are reacting with. Acyl chlorides react readily with amines due to the excellent leaving group, chloride ion.
When an amine reacts with an acyl chloride, an amide is formed almost instantly.
However, when reacting with less reactive derivatives like esters or carboxylic acids, the reaction is slower because these compounds have poorer leaving groups.

Acyl Chloride Reactivity

Acyl chlorides are among the most reactive carboxylic acid derivatives. This is because the chloride ion is a very good leaving group. When amines react with acyl chlorides, the result is the rapid formation of an amide.
The reaction mechanism involves the nucleophilic attack by the amine on the carbonyl carbon of the acyl chloride, followed by the departure of the chloride ion.
The overall process is straightforward and efficient. This is why acyl chlorides are often used as reactants in laboratories when the goal is to synthesize an amide.
Other carboxylic acid derivatives like esters, carboxylic acids, and anhydrides cannot match the reactivity of acyl chlorides due to their inferior leaving groups, making the reaction process slower and less efficient.