Carboxylic acid derivatives include anhydrides, esters, and amides.

The general chemical structure of carboxylic acid derivatives like anhydrides, amines, and esters all include a carbonyl (C=O) group. The general chemical structures for these acid derivatives are:

(eN = electronegative)

Symmetrical acid anhydrides are named like carboxylic acids except the ending acid is replaced with -anhydride. Unsymmetrical acid anhydrides are named by first naming each component carboxylic acid alphabetically arranged (without the word acid), followed by spaces, and then the word anhydride (e.g. acetic propionic anhydride). Anhydrides are usually colourless liquids.

Simple amides are named as derivatives of carboxylic acids. The –ic or –oic ending of the carboxylic acid is replaced with the suffix –amide (e.g. methanamide). Amides are usually solids.

Esters are named as if the alkyl chain connected to the O is a substituent. The name of the group attached to the carbonyl part of the ester has the –e removed and replaced with the ending –oate (e.g. ethyl ethanoate). Many fats and oils contain ester groups.

The derivatives of carboxylic acids react similarly to aldehydes because they are also electrophilic at the carbonyl carbon atom. However, unlike reactions with aldehydes and ketones, nucleophilic additions to carboxylic acid derivatives are usually followed by elimination. (Remember, addition and eliminations are opposites– while you can recognize an addition reaction because a new π bond is formed while two σ bonds break.) This is because the tetrahedral intermediate formed upon attack of the nucleophile on the carbonyl carbon has both a negatively charged oxygen atom (the former carbonyl oxygen), and a good leaving group (the eN-group of the carboxylic acid derivative). This elimination by the electrons on the oxygen atom regenerates the carbonyl, thereby displacing the leaving group (eN^–). This is called a nucleophilic addition-elimination reaction, and is sometimes referred to as an acyl substitution.

Practice Questions

Khan Academy 

Synthesis of anti-tumor drug Combretastatin and its derivatives

 MCAT Official Prep (AAMC)

Key Points

• Carboxylic acid derivatives like anhydrides, amines, and esters all include a carbonyl (C=O) group.

• Symmetrical acid anhydrides are named like carboxylic acids except the ending acid is replaced with -anhydride. Anhydrides are usually colorless liquids.

• Simple amides are named like carboxylic acids with the –ic or –oic ending replaced with –amide. Amides are usually solids.

• Esters are named as if the alkyl chain connected to the O is a substituent. The name of the group attached to the carbonyl part of the ester has the –e removed and replaced with the ending –oate. Many fats and oils contain ester groups.

• The derivatives of carboxylic acids react similarly to aldehydes because they are also electrophilic at the carbonyl carbon atom.

Key Terms

Carboxylic acid derivatives: Compounds with the acyl group, RCO-, bonded to an electronegative atom or substituent, -Y, that can act as a leaving group in substitution reactions.

Anhydrides: Any chemical compound obtained, either in practice or in principle, by the elimination of water from another compound.

Amines: Formally derivatives of ammonia, wherein one or more hydrogen atoms have been replaced by a substituent such as an alkyl or aryl group.

Esters: An organic compound made by replacing the hydrogen of an acid by an alkyl or other organic group.

Nucleophilic addition-elimination reaction: A two-stage reaction process of an addition reaction followed by an elimination reaction. This gives an overall effect of substitution, and is the mechanism of the common nucleophilic acyl substitution often seen with esters, amides, and related structures.

Acyl substitution: A class of substitution reactions involving nucleophiles and acyl compounds.