Gabriel Synthesis - Video Tutorials & Practice Problems

General Reaction

Let's talk about a really efficient way to make primary amines and that's through the Gabriel synthesis. So guys, the Gabriel synthesis is going to use a really weird looking molecule called potassium thalamide. Now I know that's like a lot of consonants at the beginning. You could kind of get jumbled up there. But just consider the pH almost to be silent. It's thalamide but it's like I don't know. You got to move your lips a little bit weird on that one. Anyway, the point here being that you need to be able to recognize this molecule, not necessarily draw it from scratch. The potassium thalidomide is a secondary diamide that can yield primary amines in much better yield. Obviously, I'm talking about something that we haven't mentioned yet. In much better yield in respect to what? What is it better at making primary amines at than what's the other reaction that we're comparing it to? What I'm talking about here is amine alkylation. If you haven't watched this video yet, it's fine. But basically, amine alkylation and Gabriel synthesis kind of very inefficient, amine alkylation whereas Gabriel synthesis is much more efficient. If you haven't watched amine alkylation yet, then you can go ahead and review it. But just letting you know, that's what I'm referring to. This is going to be really our ideal way to make specific primary amines of our choosing. What you do is you take your potassium thalidomide or just thalidomide in general and you're going to use 3 reagents. You're going to use KOH. We're going to use an alkyl halide. I'm going to put here a primary alkyl halide. That's going to become important in a second. I'm going to put here R X , a primary alkyl halide. Then finally, we're going to use hydrazine. It's NH₂NH₂. It's called hydrazine. Effectively, what winds up happening is that these all serve like their own purpose. The KOH is going to deprotonate the nitrogen and it's going to turn the thalidomide into what we call potassium thalidomide. Potassium thalidomide would actually be what it's called after the first step. It'd have an N - K+ . This happens to be an excellent nucleophile because if you think about it, N - , that's one of the strongest bases that there is. It's going to be pretty good at deprotonating stuff, attacking stuff, etc. I'm going to put here strong nucleophile. What's great about that is that now I can react this with an alkyl halide. Let's say a primary alkyl halide like here we go. A 3 carbon alkyl halide. What we can do guys is just an SN2. This is just another SN2 mechanism that you need to know. You can never forget the backside attack. Vi