Amine Alkylation

Concept: Concept: General Reaction

4m
Video Transcript

In these next few videos, I’m going to be discussing amine alkylation. By the word amine, I'm not talking about an angry alkylation. Obviously, I'm talking about the functional group amines. Now that we’ve settled that one, let's go ahead and get into the reaction.
A huge part of this section of your text, the amines portion of your text is going to be trying to figure out how to synthesize primary amines. Primary amines are useful for lots of different applications. We're always trying to figure out what's the best way to make a primary amine of my choice. The go-to reaction that we would possibly think of is why don't we use an alkyl halide because if you look at an amine, it's got a very nucleophilic lone pair. There isn't a full formal charge on this molecule at all. I'm just using the NU negative as my symbol for a nucleophile. I’ve got an electrophile which is the carbon that is attached to my halide. This opens up for a reaction that we learned a long time ago. It’s one of those mechanism you’re never allowed to forget – backside attack or SN2. Theoretically, we can make primary amines through the reaction of an amine and an alkyl halide. Let’s go ahead and just talk about this for a second. I'm not going to draw the whole mechanism but we’re just going to draw an abridged one here. You would have the lone pair doing a backside attack on my electrophilic carbon. I would kick out my leaving group. What you would wind up getting just from this very first reaction is you’d have an NH3 that's now attached to a three-carbon chain. I’m just going to write 1, 2, 3. One of the problems with that is that you're going to have a positive charge because now you have an extra bond to that nitrogen that wasn't there before. That's why we always run this reaction in a basic environment, something like NaOH. The OH negative is going to serve to deprotonate the product. So then hopefully by the end, we're actually getting our primary amine. I’ll just draw that one more time, NH2 with our three-carbon chain.
Everything seems pretty straightforward. It seems like this should be our go-to reaction for making primary amines because it’s so easy to use. I could just literally throw out any alkyl halide in there as long as it was primary or secondary or methyl and I could get an SN2. Remember that SN2s are tricky. They don’t work on tertiary alkyl halides because the leaving group is too backed up. It's too difficult to access. But we've got another problem on top of that. It's not just that SN2 has its limitations. One of the biggest problems of this reaction is that we still have a nucleophilic lone pair at the end of the reaction. Notice that your product is just as nucleophilic as it was at the beginning. What we get is a possibility of multiple alkylations. What we’re going to find is that the predominant product in these reactions is going to be a polyalkylated amine which kind of sucks if you're trying to make a primary amine. There is a way to counteract that which is to use excessive amounts of amine. If you can drown the solution with tons of your amine, and then have very little of your alkyl halide, that reduces the chances of getting multiple R groups on the same nitrogen. But it’s still quite a limiting reaction and one that we're not going to find very synthetically useful. We're going to rely on other methods of making primary amines for this reason. Let's go ahead and look at the next video. In the next video, I’m going to be explaining the entire polyalkylation mechanism of an amine.