Concept: Concept: The Primary Amines Flowchart10m
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 I’m 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. 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 six main reductions that we're going to consider to be related. They all lead to the same product which is a primary amine. Before we get into 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 looking at all these reactions, I notice 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 strong typical strong reducing agent. H2 and palladium catalysts. That would just be catalytic hydrogenation. Obviously, you could also use nickel or platinum for that. Then finally, iron and HCl which is also pretty commonly used. I’m going to refer these as the common reducing agents. I’m just going to generalize them as H in brackets. 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 three 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 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. If you want to turn an amide into a primary amine, guess which reagents we 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 the next one. Nitrile. How about if I want to turn a nitrile to pa primary amine? The common reducing agents. Awesome. 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 two equivalents. That is kind of interesting. That means whatever you're reacting with is going to work twice since this is a triple bond. You have to get rid of both of those pi bonds and you wind up getting your primary amine. Bueno. Okay, let’s keep going.
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 these. Again, the three reagents that we talked about would all work. But actually, nitro is special because I have discussed this in the past that I do have other videos talking about the reduction of nitro group. Maybe you guys might recall or maybe you haven't heard of yet that there's a chemoselective reducing aged that really just focuses in on the nitro group and it doesn't reduce any groups around it. Maybe you guys remember it, maybe you don't. I’m going to write here which one is the chemoselective one. It turns out that there's another reducing agent that you can use on nitro that is probably the ideal one to use. That’s what we call tin [ii] chloride. It’s SnCl2 and water. This is also known as stannous chloride. Stannous chloride or tin [ii] chloride, whatever. There are all different ways of saying it. But anyway, stannous chloride, tin [ii] chloride, SnCl2 over water. 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 called 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 double bond N double bond 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 to use another reagent instead and that is a triphenylphosphine, Ph3P and water. What this is going to do is it’s going to work consecutively on those nitrogens. Basically it's going to release two of them and you’re going to just get a primary amine. What about the next one? I have a question for you. Maybe you guys can integrate some other stuff that we've talked about before. What do you think about my common reducing agents here? If I took a carbonyl, 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? What do you think? No, guys. If you use, for example lithium aluminum hydride, LiAlH. If we 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 a primary degree, some kind of acid. I’m just going to put here H+. It's always going to be in an acidic environment. In the second step, you’re going to use a reducing agent that has a cyano group in it. It’s NaBH¬3CN. What wind up doing is in the first part, it's going to be kind of like an amine reaction like making an imine. 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 just 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. I’m not going to really 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 is a little 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, very important reaction. You may need to know it now; you may not need to know it now. But there is a whole separate lesson just on this one reaction. It's a very strange mechanism. The reagents for Curtius rearrangement are just going to be two things. It’s just going to be heat and water, pretty straightforward. Heat and water as you can see, it’s like how does thing turn into a primary amine? Eventually 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 in the way for that but what I’m trying to say is that these two carbons 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 gives us our primary amine. Again, not going over mechanisms here but you could search the Curtius rearrangement and then 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 product. What we’re 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. Let’s move on to the next video.
Concept: Concept: Making Amine Precursors4m
Now guys, the reason for this part of the video is because I talked about two carbonyl precursors to an amine, one was in amide and the other was the acyl halide and it turns out that both of them have a common like parent structure and that's carboxylic acid right here. So, 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 texts, okay? So, this is just again kind of a cheat sheet of how you could use carboxylic acid to make these two initial structures then you could reduce to an amine, okay? So, let's say that you wanted to make, you're starting off the carboxylic acid and you wanted to make an amide, okay? Well, that's pretty straightforward, all you have to use is NH3 okay, if you react NH3 with your carboxylic acid you can make an amide. Now, some text, some professors may want you to throw in some DCC in there, DCC is a dehydration agent that helps be yield to be stronger or better yield. So, regardless it's not a huge component of the reaction, NH3 will eventually work, if you throw in some DCC it's going to work faster, okay? Awesome, so that was easy, that's how you get to an amide, how do we get to an acyl azide? Well, there's actually no way to go straight from carboxylic acid to acyl azide, what we can do is we could use SOCl2 to convert our carboxylic acid into an acid chloride, okay? Now, remember that there are some other reagents for this or you could use PCL3 or you could use PCL5, all these reagents really do the same thing, they add, they replace an OH group with Cl. So, you could get your acid chloride, from there now this is just going to be a simple nucleophilic acyl substitution, you could just use N3 negative, okay? You could use N3 negative to basically do a substitution reaction on the chlorine and get your N3 where the chlorine was and that's your acyl acid and then you could plug that into my cheat sheet and you could say, okay, well, what would that make if I added heat and water, you know that would be a Curtius rearrangement, you would get a primary amine, alright? Awesome, and then just two more conversions that I want to show you, which is that a acid chloride doesn't just go to acyl acid, you could also make an m it just by using NH3, okay? By the way this one you definitely wouldn't need DCC with because the yield would be so high you don't need a dehydration agent and also an anhydride, which is a related functional group, if you want to start with from an anhydride you could also just use NH3, which could, which would make your amide, so the only one that you really usually have to use a dehydration agent on would be your carboxylic acid itself, okay? Awesome guys, so that was just a little refresher of how to make some related structures that then you could later reduce using the reagents that we talked about, alright? So I hope that makes sense, I hope this chart is helpful for you in a section that have a lot of random seaming reactions. So, let's move on to the next video.
Show how to synthesize the following amines from the indicated starting materials by acylation–reduction.
(a) N-butylpiperidine from piperidine
(b) N-benzylaniline from aniline
Predict the product of the following reaction.
Predict the major product for the following reaction paying attention to the regio- and stereochemistry.
Predict the product.
Draw the organic product of the following reaction. If no reaction occurs, write "No Reaction." Indicate stereochemistry where appropriate. Assume the reaction undergoes an aqueous acidic workup and neutralization.
Draw the organic product of the following reaction. If no reaction occurs, write "No Reaction." Indicate stereochemistry where appropriate. Assume all reactions undergo an aqueous acidic workup and neutralization.
Predict the product(s) for the following reaction.
Predict the product of the following reaction.
Complete the following reaction by drawing the structure of the principal organic product in the box. Draw the correct stereochemistry in the product where necessary. Be sure the product possesses the correct number of carbons and other atoms.
What sequence will yield (CH 3)3CNH2
a) (CH3)3CBr + NaN3 then LiAlH4, followed by water.
b) Phthalimide + KOH, then (CH3)3CBr, followed by H2O/OH - .
c) 2,2-Dimethylpropanoyl chloride + excess NH3, then Br2/NaOH/H2O
d) All of the above
e) None of the above
Which reaction scheme yields ethylamine?
a) React iodoethane with NaN3 followed LiAlH4 then water.
b) Treat acetamide with LiAlH4 followed by water
c) Treat CH3CH=O with ammonia and NaBH3CN
d) All of the above
e) None of the above