Question

Which conversion between carboxylic acid derivatives is NOT possible by a nucleophilic reaction? (A) Carboxylic acid to ester (B) Ester to carboxylic acid (C) Anhydride to amide (D) Ester to anhydride

Short answer

(D) Ester to anhydride

Step-by-step solution

- Understanding the Reactivity

Carboxylic acid derivatives have varying reactivities. Reactivity typically follows the order: acyl chlorides > anhydrides > esters > amides. More reactive derivatives can be converted to less reactive ones by nucleophilic substitution.

- Analyzing Carboxylic Acid to Ester

Carboxylic acids can be converted to esters through a process called esterification, typically using an alcohol and an acid catalyst. Hence, (A) is possible.

- Analyzing Ester to Carboxylic Acid

Ester can be hydrolyzed in acidic or basic conditions to yield carboxylic acid. This involves nucleophilic attack by water or hydroxide ions. Hence, (B) is possible.

- Analyzing Anhydride to Amide

Anhydrides can be converted to amides by reaction with ammonia or an amine. This is a straightforward nucleophilic acyl substitution. Hence, (C) is possible.

- Analyzing Ester to Anhydride

Converting an ester to an anhydride is challenging because it requires moving from a less reactive to a more reactive derivative, which is not typically achieved by nucleophilic substitution. Therefore, this conversion is not feasible via a simple nucleophilic reaction. Hence, (D) is impossible.

Key concepts

nucleophilic substitution

Nucleophilic substitution is a fundamental reaction type crucial in organic chemistry, especially in the context of carboxylic acid derivatives. In this reaction, a nucleophile (an electron-rich species) attacks an electrophilic carbon atom, leading to the replacement of a leaving group.
Examples of nucleophiles include water, alcohols, and amines. These reactions are integral in converting one carboxylic acid derivative to another.
For instance, the reaction of an acyl chloride with water yields a carboxylic acid, as the chloride ion is substituted by the hydroxyl group from water.
Understanding nucleophilic substitution helps in predicting the possible conversions and identifying those that are not feasible.

reactivity order

The reactivity order of carboxylic acid derivatives significantly influences their transformation efficiency. The typical order of reactivity is as follows:

• Acyl chlorides (most reactive)
• Anhydrides
• Esters
• Amides (least reactive)

This order matters because more reactive derivatives can be converted into less reactive ones via nucleophilic substitution. For example, acyl chlorides can easily be transformed into esters, amides, or anhydrides.
Conversely, converting less reactive derivatives into more reactive ones is challenging, if not impossible, through simple nucleophilic substitution.
Such knowledge is vital in predicting feasible reactions in organic synthesis.

esterification

Esterification is a key reaction to form esters from carboxylic acids and alcohols. The process involves a nucleophilic attack of the alcohol on the carbonyl carbon of the carboxylic acid.
This reaction typically requires an acid catalyst, such as sulfuric acid, to proceed efficiently. Esterification is a reversible reaction, but the removal of water promotes the formation of the ester product.
This reaction is common in organic synthesis and has many applications in producing fragrances, flavors, and plastics.
Understanding esterification helps grasp the feasibility of transforming carboxylic acids into esters.

hydrolysis

Hydrolysis is the process of breaking down a compound by reacting it with water. For esters, hydrolysis can occur under acidic or basic conditions:

• Acidic hydrolysis: The ester reacts with water, often catalyzed by an acid, yielding a carboxylic acid and an alcohol.
• Basic hydrolysis (saponification): The ester reacts with a base, such as sodium hydroxide, forming a carboxylate salt and an alcohol.

Hydrolysis is crucial for understanding the reverse reaction of esterification: converting esters back into carboxylic acids.
This reaction is essential in biochemistry for breaking down fats and oils.

acyl substitution

Acyl substitution involves replacing the acyl group (R-C=O) of a carboxylic acid derivative with another group through nucleophilic attack.
This reaction is widespread in organic synthesis and is key in converting one carboxylic acid derivative to another. For example, an anhydride can react with ammonia to form an amide.
The feasibility of acyl substitution reactions heavily relies on the reactivity order of the starting and target compounds.
Reactions moving from more reactive to less reactive derivatives are straightforward, while the reverse can be challenging.
Understanding acyl substitution helps predict feasible transformations among carboxylic acid derivatives.