Select your language

Suggested languages for you:
Log In Start studying!
StudySmarter - The all-in-one study app.
4.8 • +11k Ratings
More than 3 Million Downloads
Free
|
|

All-in-one learning app

  • Flashcards
  • NotesNotes
  • ExplanationsExplanations
  • Study Planner
  • Textbook solutions
Start studying

Acylation

Save Save
Print Print
Edit Edit
Sign up to use all features for free. Sign up now
Chemistry

You should know by now about some of the ways that carboxylic acids react (see Reactions of Carboxylic Acids for more information). In fact, they readily react like typical acids - they neutralise bases and form salts with metals or ammonia.

However, carboxylic acids don’t really take part in many other reactions. This is because they contain the hydroxyl functional group, . This particular group,, is a very poor leaving group. It isn’t stable on its own and prefers to be part of another molecule, such as a carboxylic acid. However, the close cousins of carboxylic acids, known as acid derivatives, react much more readily with a variety of substances - including in acylation reactions.

An acylation reaction is a reaction that involves adding the acyl group to another molecule.

In acylation reactions, we introduce the acyl group, , to another molecule. In this case, the acyl group comes from an acid derivative. The acid derivative is attacked by a nucleophile in an addition-elimination reaction, and the end result is the addition of the acyl group onto the nucleophile.

Don’t worry if that sounds complicated! We’ll break all those terms down in turn. We’ll then explore a mechanism for acylation using different reactants, and we’ll finish with a summary.

Let’s look at acid derivatives.

What are acid derivatives?

As the name suggests, acid derivatives are molecules very similar to carboxylic acids. You should already know that carboxylic acids have the structure , which includes the carboxyl functional group . This group in turn is made up of the carbonyl () and hydroxyl () groups. In acid derivatives, the hydroxyl group is replaced by a different group that we refer to as Z. Acid derivatives therefore have the structure .

Acylation acid derivatives StudySmarter

Acid derivatives are closely related to carboxylic acids. Anna Brewer, StudySmarter Originals

All acid derivatives are polar molecules. The oxygen atom in the double bond is a lot more electronegative than the carbon atom and attracts the shared pair of electrons towards itself, becoming partially negatively charged and leaving the carbon atom partially positively charged. Likewise, the group also tends to be more electronegative than carbon, further increasing the partial charge on the carbon atom. This is shown below.

Acylation acid derivative polarity RCOZ StudySmarterThe polarity of acid derivatives. Anna Brewer, StudySmarter Originals

We’ll focus on two common types of acid derivatives: acyl chlorides and acid anhydrides.

Acyl chlorides

Acyl chlorides have a chlorine atom as their group. This means that they all contain the functional group. They’re made by reacting a carboxylic acid with a chlorinating agent such as phosphorus(V) chloride.

To name an acyl chloride:

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

For example, ethanoyl chloride has the formula and the following structure:

Acylation ethanoyl chloride StudySmarterEthanoyl chloride. It has two carbon atoms in its carbon chain and so takes the root name -eth-. commons.wikimedia.org

Struggling with nomenclature? Check out Organic Compounds for a more detailed guide.

Acid anhydrides

Acid anhydrides are a type of acid derivative made in an elimination reaction between two carboxylic acids. This reaction also produces water.

To name an acid anhydride:

  • Find the carboxylic acid it is based on.
  • Add the word anhydride.

For example, the acid anhydride based on methanoic acid is called methanoic anhydride, and has the following structure:

Acylation methanoic anhydride StudySmarterMethanoic anhydride. commons.wikimedia.org

You’ll probably only meet simple acid anhydrides made from two molecules of the same carboxylic acid. These are simple to name - for example, the acid anhydride made from two molecules of ethanoic acid is called ethanoic anhydride. However, acid anhydrides can be made from two different carboxylic acid molecules. In this case, we list the names based on both acids in alphabetical order, followed by anhydride. For example, the acid anhydride made from one molecule each of ethanoic acid and propanoic acid is called ethanoic propanoic anhydride.

Acylation acid anhydrides StudySmarterEthanoic anhydride, left, and ethanoic propanoic anhydride, right. Anna Brewer, StudySmarter Originals

Nucleophilic addition-elimination

We learnt above that acid derivatives are polar molecules. They contain a partially negatively charged oxygen atom and a partially positively charged carbon atom:

Acylation acid derivative polarity RCOZ StudySmarterThe polarity of acid derivatives. Anna Brewer, StudySmarter Originals

This means that the molecule can be attacked by nucleophiles.

A nucleophile is an electron pair donor, containing a lone pair of electrons and a negative or partially negative charge.

In this case, nucleophiles are attracted to the acid derivative’s partially positively charged carbon atom.

Some common nucleophiles are water, alcohols, ammonia, and primary amines. They can all react with acid derivatives in nucleophilic addition-elimination reactions. These are two-step mechanisms.

  • In the first step, the nucleophile adds onto the acid derivative.
  • In the second step, the Z group is eliminated from the molecule.

We’ll explore these reactions below.

Acyl chlorides are a lot more reactive than acid anhydrides. Nucleophilic addition-elimination reactions involving acyl chlorides are vigorous at room temperature, whereas ones involving acid anhydrides are a lot slower.

Acylation of water

The first set of reactions we’ll look at involve water as the nucleophile.

Acyl chlorides

To start with, let’s take a look at the reaction between an acyl chloride and water. This is probably the simplest of the nucleophilic addition-elimination acylation reactions and shows you the reaction’s general mechanism. It produces a carboxylic acid, and hydrochloric acid, .

Acylation acyl chloride water StudySmarterAcylation of water using an acyl chloride. Anna Brewer, StudySmarter Originals

Acid anhydrides

To make acid anhydrides, we used an elimination reaction between two carboxylic acids. Reacting an acid anhydride with water is simply the reverse of this reaction. You should only have to know the reaction with a symmetrical anhydride - one made from two molecules of the same carboxylic acid. In this case, both carboxylic acid molecules are reformed.

For example, reacting ethanoic anhydride with water produces two molecules of ethanoic acid.

Acylation Ethanoic ahydride and water StudySmarterThe reaction between ethanoic anhydride and water. Anna Brewer, StudySmarter Originals

Most exam boards don’t require you to know the mechanism for this reaction, but make sure you check yours so you don’t get caught out!

Acylation of primary alcohols

The acylation reaction between acid derivatives and a primary alcohol is very similar to their reaction with water. When drawing your mechanism, simply replace one of the hydrogen atoms on the water molecule with an alkyl group.

Acylation primary alcohols StudySmarterNucleophilic addition-elimination reactions with alcohols - simply replace one of water's hydrogen atoms with an alkyl group in the mechanism. Anna Brewer, StudySmarter Originals

Acyl chlorides

Let’s take ethanoyl chloride and methanol as an example. The reaction produces hydrochloric acid and an ester, methyl ethanoate.

Acylation alcohol acyl chloride StudySmarterAcylation of methanol using ethanoyl chloride. Anna Brewer, StudySmarter Originals

Remember that when naming esters, the first part of the name comes from the alcohol. In acylation reactions, the second part comes from the acid derivative.

Acid anhydrides

When we react ethanoic anhydride with methanol, we also get methyl ethanoate. However, the second product is a carboxylic acid based on the acid anhydride. Here we get ethanoic acid.

Acylation acid anhydride alcohol acylation StudySmarterThe reaction between methanol and ethanoic anhydride. Anna Brewer, StudySmarter Originals

Acylation of ammonia

Reacting acid derivatives with ammonia produces an amide and an ammonium salt. This uses the same mechanism as the two reactions above, but there is an additional step involving an additional molecule of ammonia.

Acyl chlorides

Look at the reaction between ethanoyl chloride and ammonia. The initial reaction produces ethanamide and hydrochloric acid, but the hydrochloric acid reacts further with another ammonia molecule to produce an ammonium salt, ammonium chloride. Ammonium chloride is produced in all reactions between acyl chlorides and ammonia.

Acylation ammonia acyl chloride StudySmarterThe acylation of ammonia using an acyl chloride. Anna Brewer, StudySmarter Originals

The overall reaction is between ethanoyl chloride and two ammonia molecules, producing ethanamide and ammonium chloride.

The other product of this reaction is what we call an amide. Amides are organic molecules that contain the amine group, NH2, next to the carbonyl group, . You’ll meet them further in Amines, but we’ll briefly look at how you name amines now.

  • Count the number of carbon atoms in the carbon chain that contains the double bond - even if this chain isn’t the longest. This gives you the amine’s root name.
  • Check to see if there are any additional carbon chains attached to the nitrogen atom. If there are, name them like side chains. But instead of using a number to indicate their position, place the letter N before them. This shows that they come from the nitrogen atom instead of the carbon chain.

Amides with an additional carbon chain attached to the nitrogen atom are known as N-substituted amides.

Here, the carbon chain containing the group has one carbon atom, giving the root name -meth-. It is circled in red to help you identify it. The molecule on the left is therefore called methanamide. But the second molecule also contains an ethyl group attached to its nitrogen atom, giving it the name N-ethylmethanamide. The ethyl group is circled in blue.

Acylation methanamide N-ethylmethanamide StudySmarterMethanamide, left, and N-ethylmethanamide, right. Anna Brewer, StudySmarter Originals

Acid anhydrides

If we react an acid anhydride with an excess of ammonia, we again produce an amide. The initial reaction also produces a carboxylic acid. However, a second molecule of ammonia reacts with the carboxylic acid to produce an ammonium salt. For example, the reaction between ethanoic anhydride and ammonia produces ethanamide and ammonium ethanoate.

The reaction between ethanoic anhydride and ammonia. Anna Brewer, StudySmarter Originals

Acylation of primary amines

A lot of new information has been thrown at you, but we just need to look at one more type of reaction: reacting acid derivatives with primary amines. This is very similar to their reactions with ammonia - when you are drawing the mechanism, simply replace one of ammonia’s hydrogen atoms with an R group.

The reaction produces an N-substituted amide and a different ammonium salt.

Acyl chlorides

Reacting propanoyl chloride with methylamine gives N-methylpropanamide and methylammonium chloride.

The reaction between propanoyl chloride and methylamine. Anna Brewer, StudySmarter Originals

Acylation acylation methylamine StudySmarterThe reaction between propanoyl chloride and methylamine. The different parts of the molecules are highlighted so you can understand the reaction better. Anna Brewer, StudySmarter Originals

Acid anhydrides

Reacting propanoic anhydride with methylamine produces N-methylpropanamide too. The initial reaction also produces a carboxylic acid based off of the acid derivative. Because we started with propanoic anhydride, we produce propanoic acid. This then reacts with another molecule of methylamine to produce a different ammonium salt. Here we produce methylammonium propanoate.

Acylation acid anhydride amine StudySmarterThe reaction between propanoic anhydride with methylamine. Anna Brewer, StudySmarter Originals

Comparing nucleophilic addition-elimination reactions

Phew - you made it!

The following table should help consolidate your newfound knowledge of nucleophilic addition-elimination reactions, comparing reactants and products.

A table comparing various nucleophilic addition-elimination reactions. Anna Brewer, StudySmarter Originals

Remembering all the different reactions can be tricky. However, they all follow similar mechanisms. Instead of trying to remember each one individually, learn how to apply a few examples to a variety of different combinations of reactants.

Factors affecting acylation

Some nucleophilic addition-elimination acylation reactions happen much faster than others. This is due to many different factors.

  • The carbon atom’s partial charge.
  • The acid derivative’s Z group.
  • The strength of the nucleophile involved.

Partial charge

As we explored above, the carbon atom in the acid derivative that is joined to the oxygen atom and the Z group is partially negatively charged. The strength of this partial charge varies, depending on how electronegative the Z group is. A more electronegative Z group will attract the shared pair of electrons more strongly towards itself, increasing the carbon atom’s partial positive charge.

Imagine a tug of war between you and your friend. A piece of fabric tied around the middle of the rope represents the shared pair of electrons involved in the covalent bond between the two of you. If you are a lot stronger than your friend, you’ll be able to pull the rope and the fabric towards you. You have attracted the electrons towards yourself. We can say you are more electronegative than your friend. This leaves your friend electron-deficient and therefore partially positively charged. A carbon atom with a higher charge will be attacked by nucleophiles a lot more easily, as nucleophiles are negatively or partially negatively charged.

Leaving ability of Z group

Some Z groups are better leaving groups than others. This increases their reactivity. We won’t go into the reasons here, but it involves things like electronegativity, size and resonance. However, you should know that chloride ions are a much better leaving group than carboxylate ions, so acyl chlorides are more reactive than acid anhydrides.

Strength of nucleophile

Stronger nucleophiles will attack the acid derivative’s partially charged carbon atom more readily than weaker nucleophiles. Again, this is due to factors that we won’t go into right now, but which include charge and basicity.

We have explored reactions between acid derivatives and four different nucleophiles. These nucleophiles all vary in strength. Their relative strengths are given below:

primary amine > ammonia > primary alcohol > water

Acylation reactions involving a primary amine will therefore happen a lot faster than those involving water.

Uses of acylation

You’ll notice that reacting acyl chlorides or acid anhydrides with an alcohol produces an ester. We can also make esters by reacting a carboxylic acid with an alcohol in an esterification reaction. This is reversible, whereas acylation goes to completion. Therefore, acylation is often preferred to esterification as it gives a higher yield. However, we tend to use an acid anhydride instead of an acyl chloride to make esters for the following reasons.

  • It is cheaper.
  • It is a slower, more controlled reaction.
  • It does not produce , which is a corrosive gas.

One example of an important acylation reaction is the production of aspirin. Aspirin is manufactured by reacting a compound known commonly as 2-hydroxybenzoic acid, 2-hydroxybenzenecarboxylic acid or simply just salicylic acid, with ethanoic anhydride. This produces aspirin - an ester - and ethanoic acid.

Acylation aspirin StudySmarterThe skeletal structure of aspirin. commons.wikimedia.org

Aspirin is scientifically known as 2-acetyloxybenzoic acid, but it is also called acetylsalicylic acid, or ASA. The salicylic part of its name gives you a clue to its origins - willow trees. Willows are trees in the family Salicaceae. Chewing willow bark has been a known source of pain relief for centuries. In fact, medicines made from willow and other salicylate-rich plants are even recorded in the Ebers Papyrus from ancient Egypt!

You might synthesise and purify aspirin in class. This involves various different stages of heating, cooling, and filtering, all with the aim of getting a pure product. You can then calculate your percentage yield. It is hard to get a 100 percent yield on such a small scale in a laboratory - can you think of possible reasons why?

Acylation - Key takeaways

  • Acid derivatives are molecules that are derived from carboxylic acids. They all contain a double bond and have the general formula . Examples include acyl chlorides and acid anhydrides.
  • Acylation reactions add the acyl group, , to another molecule. In nucleophilic addition-elimination acylation, the acyl group from an acid derivative is added on to a nucleophile, producing a variety of different products.
  • Acyl chlorides are much more reactive than acid anhydrides and react readily with nucleophiles at room temperature.
  • The rate of acylation depends on the partial charge of the carbon atom, the leaving ability of the Z group, and the strength of the nucleophile used.

Acylation

Acylation is a type of reaction that involves adding the acyl group, -RCO-, to another molecule.

The acyl group is an organic group with the formula -RCO-. It consists of a carbon atom bonded to an oxygen atom with a double bond, and an R group with a single bond.

You can make acyl chlorides by reacting carboxylic acids with either solid phosphorus(V) chloride or liquid phosphorus(III) chloride.

Final Acylation Quiz

Question

What is the acyl group?

Show answer

Answer


Show question

Question

What happens in an acylation reaction?

Show answer

Answer

The acyl group is added on to another molecule.

Show question

Question

What is an acid derivative?


Show answer

Answer

A molecule derived from a carboxylic acid.

Show question

Question

Give the general formula of an acid derivative.

Show answer

Answer

RCOZ

Show question

Question

Name two types of acid derivative.

Show answer

Answer

  • Acyl chloride
  • Acid anhydride

Show question

Question

Draw the general structure of an acid derivative, showing any partial charges.


Show answer

Answer

Show question

Question

Define nucleophile.


Show answer

Answer

An electron pair donor with a lone pair of electrons, and either a negative or partial-negative charge.

Show question

Question

 Name the following acid derivative:


Show answer

Answer

Propanoyl chloride

Show question

Question

Name the following acid anhydride:

Show answer

Answer

Butanoic anhydride

Show question

Question

Acyl chlorides are more reactive than acid anhydrides. True or false? 

Show answer

Answer

True

Show question

Question

Draw the mechanism for the acylation reaction between ethanoyl chloride and water.


Show answer

Answer

Show question

Question

Draw the mechanism for the acylation reaction between ethanoyl chloride and ammonia.

Show answer

Answer

Show question

Question

The acylation reaction between an acid anhydride and water produces:


Show answer

Answer

A carboxylic acid

Show question

Question

The acylation reaction between an acid anhydride and a primary alcohol produces:


Show answer

Answer

An ester

Show question

Question

The acylation reaction between an acid anhydride and a primary amine produces:


Show answer

Answer

A secondary amine

Show question

Question

Name the products of the acylation reaction between ethanoic anhydride and methylamine.


Show answer

Answer

N-methylethanamide and methylammonium ethanoate.

Show question

Question

Name the following amide:

Show answer

Answer

N-ethylethanamide

Show question

Question

Name the following amide:

Show answer

Answer

Propanamide

Show question

Question

 Predict the products of the reaction between propanoyl chloride and ammonia.

Show answer

Answer

Propanamide

Show question

Question

A reaction between an acyl chloride and a primary amine produces N-ethylmethanamide and ammonium chloride. Name the reactants used.

Show answer

Answer

Methanoyl chloride

Show question

Question

Give a reason why producing esters using ethanoic anhydride is preferred to using ethanoyl chloride.

Show answer

Answer

Doesn’t produce HCl, which is corrosive.

Show question

Question

State three factors affecting the rate of acylation.

Show answer

Answer

  • Partial charge of carbon atom.
  • Leaving group ability.
  • Nucleophile strength.

Show question

60%

of the users don't pass the Acylation quiz! Will you pass the quiz?

Start Quiz

Discover the right content for your subjects

No need to cheat if you have everything you need to succeed! Packed into one app!

Study Plan

Be perfectly prepared on time with an individual plan.

Quizzes

Test your knowledge with gamified quizzes.

Flashcards

Create and find flashcards in record time.

Notes

Create beautiful notes faster than ever before.

Study Sets

Have all your study materials in one place.

Documents

Upload unlimited documents and save them online.

Study Analytics

Identify your study strength and weaknesses.

Weekly Goals

Set individual study goals and earn points reaching them.

Smart Reminders

Stop procrastinating with our study reminders.

Rewards

Earn points, unlock badges and level up while studying.

Magic Marker

Create flashcards in notes completely automatically.

Smart Formatting

Create the most beautiful study materials using our templates.

Sign up to highlight and take notes. It’s 100% free.