Amines by Reduction - Online Tutor, Practice Problems & Exam Prep

Primary amines can be synthesized through various reductions of nitrogen compounds, including amides, nitriles, and nitro groups, using common reducing agents like lithium aluminum hydride, catalytic hydrogenation, and iron with HCl. Special reagents, such as stannous chloride, selectively reduce nitro groups. Reductive amination converts carbonyls to amines, while the Curtius rearrangement transforms acyl azides into primary amines. Carboxylic acids can be converted to amides or acyl azides, facilitating these reductions. Understanding these reactions is crucial for effective organic synthesis.

The Primary Amines Flowchart

Hey guys. One of the most common ways that you can make amines is through the reduction of more highly oxidized nitrogen compounds. There's actually a ton of these reactions. What I'm doing in this video is grouping together a bunch of similar reductions that all generate primary amines so that you can have like a cheat sheet of similar related reductions that all lead to the same type of product. Now as a disclaimer, keep in mind that your professor may not need you to know all of these right now. But I'm banking on the fact that at some point in this course, you're going to see all these reactions in different places, so I'm grouping them together for you so that you'll think of them as similar reactions that are related to each other. Let's start off with amines by reduction. As you can see, I've got a lot of arrows here. There are 6 main reductions that we're going to consider to be related. They all lead to the same product which is a primary amine.

Now before we get into the specific reactions, I want to talk about something I'm calling the common reducing agents. This is not a term you're going to see in your textbook. But just through kind of looking at all these reactions, I noticed that there are some reducing agents that are used more often than others. The ones that are the most common are lithium aluminum hydride, which is your typical strong reducing agent, H₂ and palladium catalyst. That would just be catalytic hydrogenation. Obviously, you could also use nickel or platinum for that. And then finally, iron and HCl which is also pretty commonly used. I'm going to refer to these as the common reducing agents and I'm just going to generalize them as H in brackets. Now H in brackets always just stands for reduction in general. I'm just going to say if I write an H in brackets, that means all 3 of these reactions count as a reduction that would work here. Let's go ahead and start off on the left side of my chart and then we'll kind of move to the right side. What we're going to find is that the first few reagents are just straight common reducing agents all the way. So if you want to turn an amide into a primary amine, guess which reagents you use? You're going to use your common reducing agents. That means you could use lithium aluminum hydride. You could use catalytic hydrogenation. You could use iron and HCl. It's up to you. All of them work. Pretty easy so far.

Let's move on to the next one. Nitrile. How about if I want to turn a nitrile to a primary amine? The common reducing agents. Once again, it's the same three reagents. The same three reagents can work with a nitrile to add hydrogens to that triple bond. By the way, it is going to be 2 equivalents. That is kind of interesting. That means whatever you're reacting with is going to work twice since there's a triple bond. You have to get rid of both of those pi bonds and you wind up getting your primary amine. Good.

What do you guys think about nitro groups? A nitro group can turn into a primary amine using the common reducing agents. This chart is seeming pretty easy actually because we're using the same reagents for all of these. You can use again the three reagents that we talked about would all work. But actually, nitro is special guys because I have discussed this in the past or I do have other videos talking about the reduction of nitro groups. Maybe you guys might recall or maybe you haven't heard of yet that there's a chemoselective reducing agent that really just focuses in on the nitro group and doesn't reduce any groups around it. Maybe you remember it. Maybe you don't. I'm going to write here which one's the chemoselective one. Well, it turns out that there's another reducing agent that you can use on nitro that is probably the ideal one to use and that's what we call Tin 2 Chloride. It's SnCl₂ and water. This is also known as stannous chloride or tin chloride. What that's going to do is it's a very special reagent because it only works on nitro groups. It doesn't reduce anything else which means that we don't have to worry about protecting other vulnerable groups to reduction. It's only going to react with NO₂ which is why we call it chemoselective.

Let's move on to the other side. The other side is going to get more complicated as a heads up. If I want to turn an azide, an azide is a functional group with N triple N triple N. It's got some formal charges in there but they balance out, so there's no net charge. For azide, we're not going to be able to use the common reducing agents. We're going use another reagent instead and that is triphenylphosphine, so P₃P and water. What this is going to do is it's going to work consecutively адресующий those nitrogens to basically, it's going to release 2 of them and you're going to just get a primary amine.

What about the next one? Well, I have a question for you. Maybe you guys can integrate some other stuff we've talked about before. What do you think about my common reducing agents here? If I took carbinol, in this case, this is an aldehyde. If I took an aldehyde and I used one of the three common reducing agents on this, would I get an amine? No guys. If you use for example lithium aluminum hydride, LAH. If you use that on my aldehyde, you're going to get an alcohol. You're not going to get an amine. How do I turn a carbonyl without a nitrogen group on it, how do I turn that into a primary amine? For this, you can only use one solution, one of my favorite reactions. This is going to be reductive amination. Reductive amination is going to turn a carbonyl into a primary amine. The reagents for reductive amination are going to be some source of nitrogen. I'm just going to put NH₃, but it could be any source of nitrogen that's either a zero-degree or primary degree, some kind of acid. I'm going to put here H⁺. It's always going to be in an acidic environment. And then you're going to use in the second step, you're going to use a reducing agent that has a cyano group in it. It's NaBH₃CN. What you wind up doing is in the first part, it's going to be like making an imine. And the second part is a reduction that takes that imine and makes it into a carbonyl. I do have separate videos for some of these reactions. For example, reductive amination. If you want to know more about the mechanism, you can type in reductive amination into the search bar and then you'll find a whole video just about that one reaction. Remember, this is just a cheat sheet, so I'm not going to go through any mechanisms on this sheet. Hopefully, that one makes sense. You guys know you need to learn that one. What else? How about if I want to turn an acyl azide into a primary amine? This one's a bit more complicated. Again, we're not going to use the typical common reducing agents. This is going to be a very famous reaction called the Curtius rearrangement. Again, an important reaction. You may need to know it now. You may not need to know it now. But there is a separate whole lesson just on this one reaction. It's a very strange mechanism. The reagents for a Curtius rearrangement are just going to be two things. It's just going to be heat and water. Pretty straightforward. As you can see, it's like how does this thing turn into a primary amine? What winds up happening is that you've got your R group here, so that's your R and you've got your nitrogen here. Eventually, you wind up making a bond between those two. I know I was kind of in the way for that but what I'm trying to say is that these two carbons here wind up attaching to the one single nitrogen that remains here and you wind up getting, there you go, your primary amine because you got your two carbons. It could have been as many carbons as I wanted. But on this structure, it's two plus the nitrogen, which gives us our primary amine. Again, not going over mechanisms here but you could search the Curtius rearrangement and I'll explain that whole reaction in detail. Now we're done with all of the amines by reduction. These are all the reactions that I consider similar because they all yield the same exact products. Okay. Now what I'm going to do is in the next video, I'm going to talk about some related reactions that might help us make the initial starting product. So let's move on to the next video.

Making Amine Precursors

Now guys, the reason for this part of the video is because I talked about 2 carbonyl precursors to an amine. One was an amide and the other was the acyl azide. It turns out that both of them have a common parent structure and that's carboxylic acid right here. This section is just to serve as a reminder of some of the carboxylic acid conversions that will be in the carboxylic acid derivative part of your text. This is just again kind of a cheat sheet of how you could use carboxylic acid to make these two initial structures that then you could reduce to an amine. Let's say that you wanted to make you're starting off with carboxylic acid and you wanted to make an amide. Well, that's pretty straightforward. All you'd have to use is NH₃. If you react NH₃ with your carboxylic acid, you can make an amide. Some professors may want you to throw in some DCC in there. DCC is a dehydration agent that helps the yield to be stronger or a better yield. Regardless, it's not a

Here’s what students ask on this topic:

What are the common reducing agents used in the reduction of nitrogen compounds to primary amines?

The common reducing agents used in the reduction of nitrogen compounds to primary amines include lithium aluminum hydride (LiAlH₄), catalytic hydrogenation (H₂ with a palladium, nickel, or platinum catalyst), and iron with hydrochloric acid (Fe/HCl). These agents are effective in reducing various nitrogen-containing functional groups such as amides, nitriles, and nitro groups to primary amines.

How does reductive amination convert carbonyl compounds to primary amines?

Reductive amination converts carbonyl compounds to primary amines through a two-step process. First, the carbonyl compound reacts with a nitrogen source (e.g., NH₃) in an acidic environment (H⁺) to form an imine. In the second step, the imine is reduced using a reducing agent like sodium cyanoborohydride (NaBH₃CN), resulting in the formation of a primary amine.

What is the Curtius rearrangement and how does it produce primary amines?

The Curtius rearrangement is a chemical reaction that transforms acyl azides into primary amines. The reaction involves heating the acyl azide, which causes it to rearrange and release nitrogen gas (N₂), forming an isocyanate intermediate. The isocyanate then reacts with water to produce a primary amine.

What is the role of stannous chloride in the reduction of nitro groups to primary amines?

Stannous chloride (SnCl₂) is a chemoselective reducing agent used specifically for the reduction of nitro groups (NO₂) to primary amines. It selectively reduces the nitro group without affecting other functional groups in the molecule, making it ideal for reactions where selective reduction is required.

How can carboxylic acids be converted to amides and acyl azides for further reduction to primary amines?

Carboxylic acids can be converted to amides by reacting with ammonia (NH₃), optionally with a dehydration agent like DCC to improve yield. To form acyl azides, carboxylic acids are first converted to acid chlorides using reagents like SOCl₂, PCl₃, or PCl₅. The acid chloride then undergoes nucleophilic substitution with azide ion (N₃^-) to form the acyl azide, which can be further reduced to a primary amine.