Reactions of Amino Acids: Acylation: Videos & Practice Problems

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

In the study of amino acid reactions, acylation is a significant process that transforms the amino group of amino acids into an amide. This reaction typically involves the use of acid chlorides or acetic anhydrides as reagents, often in the presence of pyridine, which acts as a base to facilitate the reaction.

During acylation, the amino acid reacts with an acid chloride, a derivative of carboxylic acids. The reaction involves the exchange of one hydrogen atom from the amino group with an acetyl group from the acid chloride. As a result, the nitrogen atom in the amino group becomes bonded to the acetyl group, forming an amide. It is important to note that the nitrogen retains one hydrogen atom, maintaining its amine characteristics.

The preference for acylation to occur at the amine group is due to its stronger nucleophilicity compared to the carboxylate group. This means that the amine group is more reactive and more likely to interact with the acid chloride, leading to the formation of the amide. If the reaction were to occur at the carboxylate side instead, it would yield an anhydride. However, the stronger nucleophilic nature of the amine group makes the formation of an amide the favored outcome in this reaction.

Reactions of Amino Acids: Acylation Example 1

In an acylation reaction involving an acid chloride, the primary transformation is the substitution of a hydrogen atom with an acyl group. This process typically occurs with an amine, where the nitrogen atom retains one hydrogen while forming a bond with the acyl group from the acid chloride. The structure of the resulting product features an amide group, characterized by the presence of a carbonyl (C=O) directly bonded to the nitrogen atom.

To visualize this, consider the following components: the nitrogen remains connected to one of its hydrogen atoms, while it is also linked to an alpha carbon. This alpha carbon is further connected to an R group and a carboxylate group. The acyl group, which includes the carbonyl, is introduced from the acid chloride, connecting to an oxygen atom and a carbon that is still attached to a benzene ring. The final product, therefore, is an amide, formed through the interaction of the amine group and the acyl group of the acid chloride.

The general structure of the amide can be represented as follows:

R₁CONH₂

where R₁ represents the acyl group derived from the acid chloride.

Supply an anhydride needed to produce given amide. 

• A.
• B.
• C.
• D.

Answer: (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.