Carboxylic Acid Derivatives and their Reactions

Core Concepts

Carboxylic acid is a common functional group (RCOOH) that, when reacted with other molecules, become carboxylic acid derivatives. These are a group of functional groups that are nearly identical to carboxylic acid itself, but instead with a different heteroatom or group in place of the OH. Each uses carboxylic acid as a starting material, but due to different properties and reactivities, have different uses throughout organic chemistry.

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What is carboxylic acid?

Briefly, it’s important to understand carboxylic acid before moving on to its derivatives. Carboxylic acid is a functional group on organic molecules that contains both a carbonyl group and an alcohol group bonded to the same carbon, as shown below.

Due to possible resonance structures upon the removal of the H on the alcohol group (learn about resonance here!), this molecule is very stable when deprotonated. Because of this, it is fairly acidic and therefore reactive in basic and neutral conditions. For a more in depth exploration of carboxylic acid and its reactions, continue reading here.

The Carboxylic Acid Derivatives

Because of the reactivity of carboxylic acids, combining them with other things produces several other types of molecules. These molecules produced are the carboxylic acid derivatives. These derivatives are structurally very similar to carboxylic acid itself, containing a carbonyl group and another group on the same carbon. However, in the derivatives, the OH is swapped for another heteroatom or group.

This difference in the group attached to the carbon makes different reactivities among the derivatives, making each useful for different purposes. Shown below, the derivatives are in order from most to least reactive.

carboxylic acid derivatives most to least reactive — most reactive (left) to least reactive (right)

The reactivity of each derivative is determined by the stability of the leaving group, which is the the other group than the carbonyl. The molecule with the best/most stable leaving group is the most reactive derivative. Therefore, the molecule with the least stable leaving group after leaving is the least reactive.

Now, it’s time to discuss each derivative, what reactions form them, and their uses in chemistry. This is in the order of most reactive to least reactive.

Acid chlorides

Acid chloride is the most reactive carboxylic acid derivative. They are made when a carboxylic acid’s OH is replaced by a halogen, most commonly seen with Cl.

Acid chloride is the most reactive due to the stability of the chloride ion, which makes an excellent leaving group. This derivative is synthesized by the following mechanism, combining carboxylic acid with SOCl₂, which replaces the OH with Cl via a nucleophilic acyl substitution (learn the mechanism of this reaction here!).

reaction of carboxylic acid and SOCl2 to create acid chloride

Because of their high reactivity, acid chlorides react to make tons of different things, including other carboxylic acid derivatives as well as other molecules. This molecule’s versatility makes it incredibly useful in synthesis of other molecules.

Anhydrides

Anhydrides are the second most reactive carboxylic acid derivative. An anhydride is a functional group that replaces the OH of a carboxylic acid with another carboxylic acid, resulting in two carbonyls connected in the middle by a single O.

Combining a carboxylic acid with an acid chloride produces an anhydride, creating HCl as a byproduct. This can also be done with the carboxylate ion instead of carboxylic acid, which eliminates the production of HCl.

reaction of carboxylate and acid chloride to form anhydride

The reactivity of anhydrides is similar to that of acid chlorides, but the leaving group is rather unique. In this case, the leaving group consists of the entire O, second carbonyl, and the R’ group. This is a stable leaving group because of the resonance stabilization of the carbonyl group.

Anhydrides reacts similarly to acid chlorides in synthesis, but are sometimes favorable in certain reactions because they don’t hydrolyze as easily and don’t produce the corrosive HCl when reacting.

Esters

Esters are a functional group that contains merely a carbon group attached to the O rather than a hydrogen. Though, despite looking the most similar to carboxylic acids, they actually take an extra step to produce. Generally, a carboxylic acid won’t react on its own with an alcohol, but acid chlorides and anhydrides will. Once an acid chloride or an anhydride is present, simply adding any alcohol will produce an ester. However, in acidic conditions, acid acts as a catalyst and the reaction can happen from carboxylic acid to ester in just one step. Scientists call this reaction the Fischer Esterification, and it is very important to organic chemistry (learn more about it here!)

reaction of carboxylic acid and alcohol to form ester in acidic conditions, fischer esterification

Esters are not very reactive, but are known for having pleasant scents. Manufacturers often use them as ingredients in perfumes and artificial fragrances. They can also be combined with amines to make amides, though the reaction is rather slow and unfavorable.

Amides

Amides are the weakest carboxylic acid derivative. The amide functional group contains an NH₂ group in place of carboxylic acid’s OH.

It’s possible to produce amides from any of the three previous derivatives. This happens by combining each one with NH₃ or another amine. The amide is primary, secondary, or tertiary depending on the amine used.

formation of amides from acid halide and anhydride — In this image, X represents a halogen, such as Cl in an acid chloride as previously discussed.

Amides are generally not reactive enough to undergo nucleophilic substitutions like the other derivatives do because of its poor leaving group. However, they can react with water to create carboxylic acids (hydrolysis), or SOCl₂ to create nitriles.

Reduction to Aldehydes

Following the synthesis of any of these derivatives, it is also possible to further reduce to aldehyde using hydride, the H- ion. When hydride is in the presence of carboxylic acid or its derivatives, it will undergo nucleophilic attack at the carbonyl carbon, destroying the C=O double bond and then reforming it while the OH leaves the molecule, as shown below.

reduction of carboxylic acid to aldehyde via hydride

Once in the form of an aldehyde, further reduction is possible through the Wolff-Kischner reaction and Clemmensen reduction. The Wolff-Kischner reduction uses the specific reagent NH₂NH₂, which reduces a C=O all the way to only H, essentially removing the O altogether.

The other way to further reduce aldehydes is the Clemmensen reduction. The starting material and product are the same as the Wolff-Kischner, starting with a carbonyl and ending with only H in the same spot, but is instead done with ZnHg and HCl as reagents.

All of these carboxylic acid derivatives are important to organic chemistry because of how many pathways they open up when synthesizing molecules. Through these derivatives, carboxylic acid can have a leaving group of varying reactivity. This allows tons of options for how to progress through a synthesis in the most successful way possible.