Carboxylic Acid Derivatives

What are carboxylic acid derivatives?

You might already know from articles such as Carboxylic Acids that carboxylic acids have the structure RCOOH, which includes the carboxyl functional group (-COOH). The carboxyl group in turn is made up of the carbonyl (C=O) and hydroxyl (-OH) functional groups.

Acid derivatives are similar molecules. However, acid derivatives have the structure RCOZ. They still contain a carbonyl group (C=O) that is joined on one side to an organic R group; we call the RCO- combination the acyl group. But instead of the hydroxyl group (-OH) found in carboxylic acids, acid derivatives contain a Z group. The Z group is special because it always has an electronegative atom (such as oxygen, nitrogen, or sulphur) directly bonded to the acid derivative's C=O carbon atom.

Fig. 1: From carboxylic acid to acid derivative. Can you spot the difference?StudySmarter Originals

Properties of carboxylic acid derivatives

The Z group found in carboxylic acid derivatives contributes to their overall properties. For example, acid derivatives are polar. The more electronegative atom in the Z group pulls the shared pair of electrons in the C-Z bond towards itself, becoming partially negatively charged and leaving the carbon atom partially positively charged. Likewise, the oxygen atom in the C=O carbonyl group is a lot more electronegative than carbon, further increasing the carbon atom's partial charge. This is shown below.

Fig. 3: The polarity of acid derivatives is caused by their electronegative oxygen atom and Z group.StudySmarter Originals

The other physical properties of acid derivatives depend on their Z group and the length of their R alkyl chain. However, acid derivatives tend to be more soluble than some other organic molecules because their carbonyl (C=O) group can form hydrogen bonds with water.

We'll look at examples of different Z groups and the names of their parent carboxylic acid derivative families next.

Examples of carboxylic acid derivatives

Let's now introduce you to examples of carboxylic acid derivatives. We'll look at the four main types of acid derivatives, including their structures, Z group, and some common examples. Don't worry about being overloaded with new information - you might have already come across some of these molecules before without realising it!

Esters

Esters are a type of carboxylic acid derivative. Their Z group is an oxygen atom bonded to another alkyl R group, giving esters the structure RCOOR'. We call the -COO- combination of atoms the ester linkage group.

Examples of esters include methyl ethanoate (CH₃COOCH₃) and propyl methanoate (CHOOCH₂CH₂CH₃).

Fig. 4: The general structure of esters (above); examples of esters (below). Their Z group and ester linkage group are highlighted.StudySmarter Originals

Amides

Amides are another type of acid derivative. Their Z group is an amine group (-NH₂), giving them the structure RCONH₂. The combination of the C=O double bond and the amine group is known as the amide group.

The common painkiller paracetamol (also known as acetaminophen but with the tongue-twisting IUPAC name of N-(2,3,5,6-tetradeuterio-4-hydroxyphenyl)acetamide) is a great example of an amide.

Fig. 5: The general structure of amides (above); an example of an amide (below). Their Z group and the amide group are highlighted.StudySmarter Originals

Acid anhydrides

You probably haven't seen an acid anhydride before. Their name literally means without water, and it gives you a clue as to their structure. Acid anhydrides are formed when two carboxylic acids join together in an elimination reaction that releases water. They have the general structure RCOOCOR'.

You can think of acid chlorides as two acyl groups joined by an oxygen atom Z group. But for some reactions, such as in acylation reactions, it makes sense to group the entire -OCOR' chain as the Z group.

To name an acid anhydride in accordance with IUPAC nomenclature:

• Find the carboxylic acid(s) it is based on.
• Add the suffix -anhydride.

For example, the acid anhydride formed from two molecules of methanoic acid is known as methanoic anhydride, whilst the acid anhydride formed from one molecule of ethanoic acid and one molecule of propanoic acid is called ethanoic propanoic anhydride.

Fig. 6: The general structure of acid anhydrides (above); examples of acid anhydrides (below). Their Z group is highlighted.StudySmarter Originals

Acyl chlorides

Finally, let's look at acyl chlorides. They're a type of acyl halide - an acid derivative with a halogen atom Z group. It'll come as no surprise to you that in acyl chlorides, the halogen atom is a chlorine atom. Acyl chlorides have the general structure RCOCl.

To name an acyl chloride in accordance with IUPAC nomenclature:

• Count the number of carbon atoms in its parent carbon chain and give it the appropriate root name.
• Add the suffix -oyl chloride.

An example of an acyl chloride is ethanoyl chloride. It is commonly known as acetyl chloride and so you might see it referred to with the abbreviation AcCl.

Fig. 7: The general structure of acyl chlorides (above); an example of an acyl chloride (below). Their Z group is highlighted.StudySmarter Originals

Preparation of carboxylic acid derivatives

Moving on - time to focus on the preparation of carboxylic acid derivatives. In particular, we'll look at how we make acyl chlorides, but we'll also consider the preparation of other acid derivatives.

Preparation of acyl chlorides

We synthesise acyl chlorides by reacting a carboxylic acid with either phosphorus(V) chloride (PCl₅), phosphorus(III) chloride (PCl₃), or sulphur dichloride oxide (SOCl₂).

• Reacting carboxylic acids (RCOOH) with phosphorus (V) chloride produces an acyl chloride (RCOCl), phosphoryl chloride (POCl₃), and hydrogen chloride gas (HCl). This reaction takes place at room temperature.
• Reacting carboxylic acids with phosphorus (III) chloride produces an acyl chloride and phosphorous acid (H₂PO₃). This reaction requires heat.
• Reacting carboxylic acids with sulphur dichloride oxide produces an acyl chloride, sulphur dioxide (SO₂) and hydrogen chloride gas (HCl). This reaction takes place at room temperature.

Here are the respective equations for the three reactions:

$$RCOOH+PCl_5\rightarrow ROCl+POCl_3+HCl$$

$$3RCOOH+PCl_3\rightarrow 3ROCl+H_3PO_3$$

$$RCOOH+SOCl_2\rightarrow ROCl+SO_2+HCl$$

Preparation of other acid derivatives

Here are some of the ways of making other acid derivatives:

• Amides can be formed by reacting an acyl chloride or acid anhydride with ammonia or a primary amine. This is a nucleophilic addition-elimination acylation reaction, and we look at it in more detail in the section below on the reactions of carboxylic acid derivatives.
• Esters can be formed by reacting a carboxylic acid with an alcohol in an esterification reaction. They're also made by acylating alcohols using an acyl chloride or acid anhydride (which, once again, is another example of an electrophilic addition-elimination reaction).
• Acid anhydrides can theoretically be made in a dehydration reaction between two carboxylic acids. However, there are much more efficient (if slightly roundabout) ways of producing them!

Reactions of carboxylic acid derivatives

Remember how at the start of the article, we mentioned that carboxylic acids aren't that reactive? For example, they require both an acid catalyst and heating in order to react with alcohols. However, particular types of acid derivatives are much more reactive. For example, acyl chlorides react vigorously with alcohols at room temperature!

We'll now turn our attention to the reactions of acid derivatives. But before that, we'll first find out about their relative reactivity.

Reactivity of acid derivatives

Not all acid derivatives are as reactive as each other. In fact, some of them are less reactive than carboxylic acids themselves! Here's a diagram showing the relative reactivity of carboxylic acids and their four main acid derivatives. You can see that acyl chlorides are the most reactive whilst amides are the least.

Fig. 8: The relative reactivity of acid derivatives. Acyl chlorides are the most reactive whilst amides are the least.StudySmarter Originals

Moving on - here are a selection of reactions of acid derivatives themselves.

Nucleophilic addition-elimination acylation reactions

Acyl chlorides and acid anhydrides react with various nucleophiles in nucleophilic addition-elimination acylation reactions. Acylation reactions introduce the acyl group (RCO-) to another molecule. In nucleophilic addition-elimination reactions, as the name suggests, the acylated molecule is a nucleophile.

The products and conditions of nucleophilic addition-elimination acylation vary depending on the combination of reactants, but we can generalise the reactions with the following equation:

$$RCOZ+NuH\rightarrow RCONu+HZ$$

Fig. 9: The structures of the species involved in the general equation for a nucleophilic addition-elimination acylation reaction. Their acyl groups and Z groups are highlighted.StudySmarter Originals

Note that the Z group acts as a leaving group - it splits off from the rest of the acid derivative. The Z group then forms an acid by combining with hydrogen from the nucleophile. In certain reactions, this acid reacts with another molecule of the nucleophile to form a salt.

Here's a handy table that summarises the different reactions. Notice that the reactions involving acyl chlorides take place at room temperature whilst the reactions involving acid anhydrides require heating. This is because acyl chlorides are more reactive than acid anhydrides, as we looked at earlier.

Table 1: Nucleophiles, acyd chlorides and acid anhydrides.

Friedel-Crafts acylation reactions

Friedel-Crafts acylation reactions are another type of acylation reaction involving acyl chlorides or acid anhydrides. They introduce the acyl group (RCO-) to benzene or another aromatic molecule.

Friedel-Crafts acylation reactions are examples of electrophilic substitution reactions and involve an aluminium chloride catalyst. They all produce an aromatic ketone and an acid with the structure HZ, where Z is the acid derivative's Z group. Once again, the Z group acts as a leaving group:

• Acyl chlorides react with benzene to produce an aromatic ketone and hydrochloric acid (HCl).
• Acid anhydrides react with benzene to produce an aromatic ketone and a carboxylic acid (RCOOH).

Here's the general equation:

$$RCOZ+C_6H_6\rightarrow C_6H_5COR+HZ$$

Fig. 11: The structures of the species involved in the general equation for a Friedel-Crafts acylation reaction. Their acyl groups and Z groups are highlighted.StudySmarter Originals