Curtius Rearrangement - Online Tutor, Practice Problems & Exam Prep

The Curtius rearrangement is a synthetic pathway that transforms acyl azides into primary amines through a two-step process involving heat and water. Initially, heat induces the formation of isocyanate from the acyl azide, a reactive intermediate. The subsequent addition of water leads to the formation of carbamic acid, which undergoes decarboxylation, releasing CO₂ and N₂ gases. This reaction is significant in organic synthesis for generating amines while eliminating a carbon atom, showcasing the utility of isocyanates in various organic reactions.

General Mechanism

Hey guys. In this video, we're going to talk about a really important synthetic pathway called the Curtius rearrangement. This reaction does go by another name. It's also called the reduction of acyl azide. That name really describes what's going on here. An acyl azide is a functional group that has a carbonyl, an R group and then N₃ on one side. That's an azide. If you can reduce this molecule and get the carbonyl to come off, what we're going to wind up getting is we're going to wind up getting a primary amine. This is going to require a really interesting rearrangement for that to take place. There are only 2 reagents in this reaction. There's heat and there's water. You might think that it's a really easy mechanism, but actually, it's really strange because of the fact that atoms are rearranging and we're going to have a reactive intermediate called a nitrene that isn't really commonly seen in orgo. We're going to definitely make sure to handle that in the mechanism part. What are the 2 steps? The first step is heat. Heat is going to drive the rearrangement of this molecule here into isocyanate. Now isocyanate is its own topic within organic chemistry. There are a lot of reactions that we can do with isocyanate. But for right now, this is just going to be the middle structure that we use, the intermediate structure that we then react with again to get our primary amine. What's our second step? Our second step is the addition of water to that isocyanate. That's going to result in a decarboxylation reaction and it's going to liberate 2 gases at the end. It's going to liberate CO₂ gas because decarboxylation reactions always liberate CO₂ gas and we're also going to liberate N₂ gas from the decomposition of the acyl azide in the first step. Now I have mentioned a few terms here. For example, decarboxylation. That's a mechanism that I teach in a separate video. If you want to know more about what a decarboxylation reaction is, you can always just type it into the Klutch search bar and you'll find that video. That being said, let's go ahead and just dive into this mechanism and see what it's all about. I already showed you guys what an acyl azide looks like. When you draw it out in bond line structure, this is what you're going to get. That's the most common way that it's represented. It's N double bond N double bond N and with the formal charges accordingly. But guys, this azide has a resonance structure, and that resonance structure has to be taken into account. That resonance structure would be that the negative charge could make a triple bond. That would already have 3 bonds on one side. That means I only need 1 more bond on the other, or I'd be violating the octet. If I make this bond, I'm going to break this bond and form a lone pair on that nitrogen. That means that the resonance structure on the other side looks something like this. I've got a triple bond here, a negative charge here because I added an extra lone pair, and I still have a positive in the middle because it still has 4 bonds. Nothing changed for that middle nitrogen. What's interesting here guys is that usually, these resonance structures both exist. They're both averaging into the hybrid. But in the presence of heat, one of these resonance structures is going to influence the character of the molecule more than the other. The reason is that we can have a decomposition reaction. Heat is going to make this decompose. And the reason is that this resonance structure, the second one, looks a whole lot like N₂ gas. N₂ gas is just N triple bond N and it composes 78% of the atmosphere. If 78% of the atmosphere is N₂ gas, do you think it's stable or unstable? It's highly stable, guys. I mean you're breathing it in constantly. It's not reacting with you, is it? Or not too much. This is a very stable entity. And if you can become N₂ gas, you're like in chemical Nirvana. That's like the best thing you can do. Look at this resonance structure. It's one bond away from being N₂ gas. In heat, what you're going to get is a decomposition reaction where these electrons pick up and leave as a lone pair. What you wind up getting is now your n with just 2 lone pairs and nothing else, R plus your N₂ gas. This molecule product, it's really an intermediate because it has the right number of valence electrons. Remember that nitrogen wants to have 5? It has 5. But this is highly reactive because it's not filling its octet. This nitrogen only has 6 octet electrons. If you were to count, lone pair is 2, lone pair is 2, the bond is 2, that's 6. We need 8. This is a very reactive intermediate called a nitrene. It turns out this nitrene is going to want to rearrange. This is the Curtius rearrangement part. What we're going to get is that the R group, the electrons from the R group actually attach to the N. A lone pair comes down and forms a double bond. This is just going to be our rearrangement. And what we wind up getting is our isocyanate as a product. I'm going to have O double bond C, double bond N with now an R group coming off of it. This is a molecule called isocyanate, which as I alluded to earlier, is actually a really important molecule in organic chemistry. There are a lot of different addition reactions we can do to this. But for this mechanism, we're only going to do 1 and that's going to be the addition of water. You could end this here. If all you did was you added heat to an acyl azide, you'd get isocyanate and you'd be done. But we want to get a primary amine. Essentially, we want to liberate this part. All we want is the NR component. We don't want the carbon. We don't want the O. How can we get rid of that if we add water? In my second step, I add water. Can you guys predict which atom the water will be most attracted to in a nucleophilic attack? What do you guys think? You got it. We're going to attack the carbon, carbonyl carbon. We're going to push the electrons down to the end. What this is going to give us is a molecule that looks like this. OHNR, and eventually, this is going to get an H because it's going to form a negative charge and it's going to protonate. This is called Carbamic acid. What's special about carbamic acid is that it is very unstable. It's not a stable molecule, so it can spontaneously decarboxylate. Now again, for more on the mechanism of decarboxylation, search that topic individually. But we'll just draw it as it relates to this molecule here. This is going to be our decarboxylation. What we're going to do is that the nitrogen, let me actually draw this H sticking out so it's going to be easier. This nitrogen grabs the H. Make a bond. Break a bond. We're going to take the electrons from this single bond and donate them to the bond between the O and the C. Now that that carbon has 4 bonds, the carbonyl carbon, we're going to use these electrons to make a lone pair on the end. It's a weird reaction. But notice what you get at the end. What you're going to get is now a nitrogen with an R group with how many H's? 2. You've got the original H, and we've got the new H that we grabbed. What else do we have? Well, we also have carbon with now a double bond O and a double bond O. Do you guys know what that is? The product of a decarboxylation is always CO₂ gas. We just created 2 different gases. One of them is a greenhouse gas. Oh no. Hurting the environment. Hopefully it's you know, we're keeping it in the lab though. Guys, this is really interesting. We've just made CO₂ gas. We've made N₂ gas here and here. But most importantly and what your professors will be most interested in is that we made a primary amine. That primary amine also lost a carbon. This is going to be an interesting synthetic reaction that we use when we're trying to get an amine and we're trying to lose a carbon. I'll show you guys why you would want to use that in a second. This is a really great reaction to use. It looks complicated, but it's actually used more often than you think in organic chemistry. That being said, that’s the whole mechanism. I hope that made sense. Let's go ahead and look.

Propose a Synthesis

Right, guys. Maybe you didn't know it, and that's okay. But what I do want to emphasize here is that this pathway that I'm showing you is one of the more important pathways for aromatic synthesis and it's one of the fastest ways that you can make aniline because if you recall, I've never taught you an EAS mechanism for aniline. We have to get creative when we want to make it. The first thing you'd do is you'd add an R group. That was already done for you. We already have an R group there. If you wanted to add an R group, hopefully you could remember some reactions that you could use to add R groups. For example, Friedel Crafts alkylation. But now that the R group is there, what can we do? We want to turn this into an acyl azide to rearrange. The first step to doing that would be a carboxylic acid. Let's go ahead and do a side chain oxidation with KMnO₄. Now I'm already noticing I'm going to run out of room in this box because KMnO₄, you could write it, but some professors want to see every single reagent, so let's write that out. It's going to be in base with heat/over acid. KMnO₄ is the short way to put it, but now I just included all the reagents. What that's going to do, guys, is that's going to add a carboxylic acid here. Remember that you always pretty much can oxidize any side chain to a carboxylic acid as long as it has at least one hydrogen on it, which it did. Perfect. The second step would be let's figure out a way to make this an acyl azide. We have to put an N₃. The next step would be to use SOCl₂. SOCl₂ is a very common reagent to turn carboxylic acids into acid chlorides. Now I've just kind of heightened the reactivity of my carboxylic acid derivative. The next two reactions that you're going to find come mostly from your carboxylic acid derivative section of organic chemistry. If you want to brush up on any of these reactions, feel fr

Here’s what students ask on this topic:

What is the Curtius rearrangement and what are its key steps?

The Curtius rearrangement is a synthetic pathway that converts acyl azides into primary amines. The process involves two key steps: first, heating the acyl azide to form an isocyanate intermediate, and second, adding water to the isocyanate, which leads to the formation of carbamic acid. This carbamic acid then undergoes decarboxylation, releasing CO₂ and N₂ gases, and resulting in the formation of a primary amine. This reaction is particularly useful in organic synthesis for generating amines while eliminating a carbon atom.

What are the reagents required for the Curtius rearrangement?

The Curtius rearrangement requires only two reagents: heat and water. Heat is used in the first step to drive the rearrangement of the acyl azide into an isocyanate intermediate. Water is then added in the second step to react with the isocyanate, leading to the formation of carbamic acid, which subsequently undergoes decarboxylation to produce a primary amine.

What is the role of isocyanate in the Curtius rearrangement?

In the Curtius rearrangement, isocyanate serves as a key intermediate. It is formed in the first step when heat is applied to the acyl azide. The isocyanate then reacts with water in the second step to form carbamic acid. This carbamic acid is unstable and undergoes decarboxylation, releasing CO₂ and N₂ gases, and ultimately yielding a primary amine. The isocyanate intermediate is crucial for the transformation of the acyl azide into the desired amine product.

What gases are released during the Curtius rearrangement?

During the Curtius rearrangement, two gases are released: carbon dioxide (CO₂) and nitrogen (N₂). CO₂ is released during the decarboxylation of carbamic acid, while N₂ is liberated from the decomposition of the acyl azide in the first step. These gas releases are indicative of the reaction's progression and are important for the overall transformation of the acyl azide into a primary amine.

How does the Curtius rearrangement differ from the Hofmann rearrangement?

Both the Curtius and Hofmann rearrangements convert amides into amines with the loss of a carbon atom, but they differ in their starting materials and mechanisms. The Curtius rearrangement starts with an acyl azide and involves the formation of an isocyanate intermediate, whereas the Hofmann rearrangement starts with an amide and involves the formation of an isocyanate via a nitrene intermediate. Additionally, the Curtius rearrangement requires heat and water, while the Hofmann rearrangement typically uses bromine and a strong base like sodium hydroxide.