Reactions of Amino Acids: Acylation - Online Tutor, Practice Problems & Exam Prep

Acylation is a reaction that transforms the amino group of amino acids into an amide using acid chlorides or acetic anhydrides as reagents, often in the presence of pyridine. This process occurs at the amine group, which is a stronger nucleophile than the carboxylate group, leading to the formation of an amide. If the reaction had occurred at the carboxylate side, an anhydride would have formed instead. Understanding this mechanism is crucial for grasping nucleophilic acyl substitution and the reactivity of amino acids in organic synthesis.

Reactions of Amino Acids: Acylation Concept 1

Hey everyone. So in our discussion of reactions of amino acids, we take a look at acylation. Now, acylation converts the amino group of amino acids into an amide. And we're going to say here that the acid chloride that we have, so acid chlorides and acetic anhydrides are used as reagents alongside our pyridine. Now, here we have our amino acid.

We're going to use here an acid chloride. So remember, this is one of our carboxylic acid derivatives over our purity. And what happens in the process is we're going to have one of these hydrogens being exchanged for this portion here, this Acetyl group right here. So we're still going to have a hydrogen that's still up on Nitrogen. Then Nitrogen now is going to be connected to this Acetyl group.

And in that way, what we've just created is an amide group. Now, we're going to say acylation occurs at the amine group because it's a stronger nucleophile than the carboxylate group. Right. So just remember, this could have happened on either side. It happened on the amine side to create an amide.

If it had occurred on this side, then we would have gotten an anhydride. But again, the amine group is a stronger nucleophile, so it's more likely to interact with this acid chloride. And thus, giving us an amide at the end.

Reactions of Amino Acids: Acylation Example 1

Here in this example, it says, provide the product of the following acylation reaction. Now remember, in this type of reaction, all that occurs is that one of the hydrogens is substituted out for the acyl group of this acid chloride, so this portion right here. So we're going to have still this nitrogen connected to one of its H's. We're still going to be connected to this alpha carbon here, connected to this R group, connected to this carboxylate group. And, again, we're going to introduce this carbonyl, which is this carbonyl, which is connected to this O, connected to this carbon, which is still connected to this benzene.

Alright. So, this would be our final product. An amide group has been formed through the interaction of the amine group and the acyl group of this acid chloride.

Supply an anhydride needed to produce given amide. 

• A.
• B.
• C.
• D.

Here’s what students ask on this topic:

What is acylation in the context of amino acids?

Acylation in the context of amino acids refers to the chemical reaction where the amino group (–NH₂) of an amino acid is converted into an amide (–CONH₂). This transformation is typically achieved using reagents such as acid chlorides or acetic anhydrides, often in the presence of a base like pyridine. The amine group is a stronger nucleophile compared to the carboxylate group, making it more reactive towards acylation. This process is crucial for understanding nucleophilic acyl substitution and the reactivity of amino acids in organic synthesis.

Why is the amine group more likely to undergo acylation than the carboxylate group?

The amine group (–NH₂) is more likely to undergo acylation than the carboxylate group (–COO⁻) because it is a stronger nucleophile. Nucleophiles are species that donate an electron pair to form a chemical bond. The nitrogen atom in the amine group has a lone pair of electrons that is more readily available for bonding compared to the oxygen atoms in the carboxylate group. This makes the amine group more reactive towards electrophiles like acid chlorides or acetic anhydrides, leading to the formation of an amide.

What reagents are commonly used in the acylation of amino acids?

In the acylation of amino acids, the most commonly used reagents are acid chlorides and acetic anhydrides. These reagents react with the amino group of the amino acid to form an amide. The reaction is often carried out in the presence of a base such as pyridine, which acts as a catalyst and helps to neutralize the hydrochloric acid or acetic acid by-products formed during the reaction. This setup ensures a smooth conversion of the amino group into an amide.

What is the role of pyridine in the acylation reaction of amino acids?

Pyridine plays a crucial role in the acylation reaction of amino acids. It acts as a base and a catalyst. As a base, pyridine neutralizes the hydrochloric acid or acetic acid by-products formed during the reaction, preventing them from interfering with the reaction. As a catalyst, pyridine helps to activate the acid chloride or acetic anhydride, making them more reactive towards the amino group. This dual role of pyridine ensures a more efficient and smoother acylation process, leading to the formation of the desired amide.

What would be the product if acylation occurred at the carboxylate group instead of the amine group?

If acylation occurred at the carboxylate group (–COO⁻) instead of the amine group (–NH₂), the product would be an anhydride instead of an amide. The carboxylate group would react with the acid chloride or acetic anhydride to form a new anhydride linkage (–CO–O–CO–). However, this is less likely to happen because the amine group is a stronger nucleophile and more reactive towards acylation reagents, making the formation of an amide the more common outcome.