Acylation of Aniline - Online Tutor, Practice Problems & Exam Prep

Aniline, being a highly activated benzene due to its amino group, poses challenges in electrophilic aromatic substitution (EAS) reactions, leading to polysubstitution. To mitigate this, acetylation is employed, where an acyl chloride reacts with aniline in the presence of a base like pyridine, forming a moderately activated acetylated amine. This allows for controlled nitration, predominantly yielding para products. The acetyl group can later be removed through hydrolysis, restoring the aniline structure with the desired substituent. Always consider protection when working with aniline to avoid unwanted reactions.

Synthesize the target molecule

This is a very typical multi-step synthesis problem that you would face in this chapter. There's a lot going on. The first thing that we notice is that first of all, none of the substituents on the first molecule are on the second. We either have to figure out how to remove them or how to transform them. In the case of the nitro, do we know any ways to transform a nitro group into an amino group? Hell yeah. We do. We'll come back to that in a second. Now we are also adding a chlorine. Do we now have the tools to add chlorine to a benzene ring? Yep, that's Electrophilic Aromatic Substitution (EAS). You might be wondering why this takes 4 steps. If you're getting aniline, if you're working with aniline, you're going to have to protect it. Let's start off at the beginning. What do you think the first reagent should be? For example, can my first reagent be an EAS chlorination? Should I do that first? No, guys, you can't because if you chlorinate right now, you have a meta director. You're going to wind up getting a chlorine here. Is that what we want? No. We need to transform it to an ortho/para director first, meaning that I have to reduce it first. Now you could use any of the reducing agents that I've mentioned in the past. All of them will be correct. I'm going to use the stannous chloride. I told you guys that's my personal favorite. I've got my tin chloride SnCl₂ and water. What that's going to give me is my aniline. I'm just going to draw it on this side.

Okay. So now I've got my aniline in place. Can I just do a chlorination? No, I can't. Before this topic, you would have and you would have thought you're doing great. But now because of this topic, we know that you need to acetylate or protect the amino group before we can keep reacting with it. What we're going to do is we're going to add CH₃COCl over pyridine. What that's going to give us is now a molecule that look

Here’s what students ask on this topic:

What is the purpose of acetylation in the acylation of aniline?

Acetylation is used to protect the highly reactive amino group in aniline during electrophilic aromatic substitution (EAS) reactions. Aniline is so reactive that it can lead to polysubstitution, which is undesirable. By acetylating aniline, the amino group is converted into an acetylated amine, which is moderately activated. This allows for controlled reactions, such as nitration, to occur predominantly at the para position. After the desired substitution, the acetyl group can be removed through hydrolysis, restoring the aniline structure with the desired substituent.

How does acetylation affect the reactivity of aniline in EAS reactions?

Acetylation reduces the reactivity of aniline in EAS reactions by converting the highly activating amino group into a moderately activating acetylated amine. The acetyl group introduces a carbonyl group adjacent to the nitrogen, which decreases the electron-donating ability of the nitrogen's lone pair. This makes the benzene ring less reactive, preventing polysubstitution and allowing for more controlled and selective reactions, such as nitration, to occur.

What reagents are used in the acetylation of aniline?

The acetylation of aniline typically involves the use of an acyl chloride (such as acetyl chloride) and a base. Pyridine is a commonly used base in this reaction because it is aromatic and can effectively catalyze the reaction. The general reaction involves the aniline reacting with the acyl chloride in the presence of pyridine to form the acetylated amine.

How can the acetyl group be removed after the desired substitution in aniline?

The acetyl group can be removed from the acetylated amine through a process called hydrolysis. This involves treating the acetylated compound with a base, which hydrolyzes the acetyl group, restoring the original aniline structure with the desired substituent. This step is crucial to revert the protection and obtain the final product.

Why is it necessary to protect aniline before performing EAS reactions?

It is necessary to protect aniline before performing EAS reactions because the amino group in aniline is highly activating, making the benzene ring extremely reactive. This high reactivity can lead to polysubstitution, where multiple substituents are added to the ring, resulting in unwanted products. By protecting the aniline through acetylation, the reactivity is reduced, allowing for more controlled and selective reactions to occur, preventing polysubstitution and ensuring the desired product is obtained.