Nitrogenous Nucleophiles

Concept: Concept: Four Ways to Make a Primary Amine Precursor

8m
Video Transcript

If you’ve watched my amines by reduction video already, then you’ll know how important reduction reactions are to making primary amines. If you haven't watched already, you need to go back and watch it because the concepts in this video are going to build upon the cheat sheet that I taught you in that one. In this video, what we’re going to discuss is how you don't always have to start with those highly oxidized nitrogen compounds to get to a primary amine. Sometimes you can start off with just an alkyl halide and use nitrogen in an SN2 reaction to get to a primary amine eventually.
Let’s check this out. Three of the reagents that were the starting compounds in my amines by reduction video can be found as excellent nucleophiles. It turns out that some of the ways that we can make those oxidized nitrogen compounds is to use nitrogen as a nucleophile first in an SN2 reaction. That’s what we’re going to write here. They're going to participate in SN2 reactions because it works if there's a good leaving group present. Obviously, maybe it's been a while since SN2 so you might need to brush up a little bit but it's really easy. It’s backside attack. Let me just show you an example of what I'm talking about and then maybe you'll understand more of what I’m saying. Here I have a secondary alkyl halide. What we learned back with SN2 is that SN2 is favored for secondary alkyl halides if you have a strong nucleophile, if you have a good nucleophile, something that’s good at donating electrons. A really easy way to put a nitrogen where that bromine is is to react it for example with CN negative. Remember, CN negative is a strong nucleophile that we used plenty in Organic Chemistry 1. This would do a backside attack. It would attack the backside. It would kick out the bromine. What would you get as a consequence? We would get a product that now looks like this. C triple bond N. Now that we have a nitrile, how can I turn this into a primary amine? Do you guys remember any reagents that would work on this to make it into a carbon with an NH2? I’ll put the H at the bottom. Perfect. What reagents could we use to turn a CN group into a primary amine? This is our common reducing agents. What I'm trying to do is I’m trying to take you a step backwards. I’m trying to say if you don't have an nitrile already, what nucleophile could we use to get there? Now I’m going to show you some other ones. CN is a possibility. Can you think of any others? How about NO2 negative? NO2 negative is a strong nucleophile that we've used before. It can also do you a backside attack and we would get a nitro group.
How can we reduce nitro into an amine? What reagents could we use for that? Again, we can use our common reducing agents. Do you guys remember maybe a more chemoselective reduction that’s only going to work on the NO2? In case you didn’t or maybe you did, it’s your stannous chloride. It’s going to be your tin[II] chloride. Your tin[II] chloride is your chemoselective version that's just going to pick the NO2 moiety and it's just going to reduce that. What’s another nucleophile? Wrack your brain. Think what's another of those six reduction reactions. What’s another one that we could make through an SN2 reaction? Maybe you thought about it already. We could make an azide because N3 negative is a strong nucleophile. We could do a backside attack. What that would give us is a compound that looks like this, N3. What reagents could we use on N3 to turn it into a primary amine? The answer guys, this one’s a little bit weird. We can't use the common reducing agents. We would have to use your triphenylphosphine and water. The point of this whole lesson here is that I want to show you that you don't always need to start off at these middle steps. You don’t always have to start off with an azide. You can create an azide through SN2 by using the nucleophilic properties of those nitrogens.
On top of that, there's one more that we can't make through an SN2 but we can still make it through negatively charged species and that is N3 negative. Remember that N3 negative can do a substitution reaction with an acid chloride. This isn't the full mechanism but this is like the abridged mechanism. The full mechanism is called nucleophilic acyl substitution. That one you can look up on your own. You can type in nucleophilic acyl substitution into the Clutch search bar and you’ll find a whole video on that. So I have here N3 negative. It can act on acid chloride to produce acyl azides. Like I said, it's no-SN2 mechanism but we talked about it in another video. It's an NAS mechanism. What you wind up getting is acyl azide. Do you guys remember how you can turn an acyl azide into an amine? This one would look like this. What reagents could you use for that? This one would be the Curtius rearrangement. The reagents for Curtius were just heat and water. Just showing you guys how you don't always have to start off with that highly oxidizing nitrogen. You can add the nitrogen because nitrogen is in a lot of nucleophilic compounds.
What I want you to do next is just go ahead and do this practice problem. See how far you can get. I will warn you guys that the third reagent, I’m just going to tell you right now. This is a reaction called a diazonization. You might not know it yet depending on if you've watched this video or not. If you don't know the last one, no hurt feelings. Just go ahead and watch me solve it. But at least you should be able to do the first two. Then I'll go ahead and finish up the last part for you guys. Go ahead and do it.