Synthesis of Amino Acids: N-Phthalimidomalonic Ester Synthesis - Online Tutor, Practice Problems & Exam Prep

Synthesis of Amino Acids: N-Phthalimidomalonic Ester Synthesis Concept 1

Hey, everyone. So in this video, we're going to talk about amino acid synthesis and in particular, the N-Beta-methylamino malonic ester synthesis. Now, you're going to say that N-Beta-methylamino malonic ester synthesis combines the Gabriel synthesis and malonic ester synthesis. Now, here, it's going to take place in 4 steps. So we have steps 1, 2, 3, and then we have steps 4a and 4b.

These are steps 4 which are just segmented into 2 parts. Now, if we take a look here, we're going to say step 1 deals with an SN2 reaction. Here, we're going to say potassium ethylamide reacts with an alpha bromomolonic ester. Alright. So here we have our potassium ethylamide, which remember is a key ion key molecule in terms of the Gabriel synthesis.

We're going to say here, it's going to hit this alpha carbon and kick out the bromine. And we're going to say here, when we do that, that's going to create this, which is our N-methylamidomelonic ester. Next step 2, we have enolization. We're going to say a strong base deprotonates the alpha carbon of N. So here's our strong base here.

We're going to say, here's our alpha carbon still. This is going to come and deprotonate. We're going to say here the alpha carbon holds on to the electrons. So next, we're going to say for step 3, so again this negative carbon here. Step 3 is alkylation of the enolate.

So the enolate anion attacks an alkyl halide in an SN2 mechanism or SN2 reaction. So this is going to come in with its lone pairs. It's going to hit this carbon, kicking out the halogen by SN2. So what we've just done is we've alkylated the alpha carbon. So we've created an alkylated and N-methylamidomelonic ester.

Then we go to steps 4a and 4b. We're coming back up here. 4a, we have the imide and the esters are hydrolyzed for hydrolysis. And in decarboxylation, we're going to say one of the carboxylic acid groups is lost to CO₂. So if we come back down here, we have our H₃O⁺ which is acid hydrolysis and heat.

That'll change my esters into carboxylic acids. And then we're going to introduce this heat later here in step 4b, which causes decarboxylation, so we lose CO₂, this one here. And that's how we wind up with this amino acid at the end. Here's our alpha carbon, the methyl group that we've attached, our amino group, and our carboxylic acid. Right?

So this is yet another process that we can employ in order to make amino acid.

Synthesis of Amino Acids: N-Phthalimidomalonic Ester Synthesis Example 1

Hey, everyone. In this example question, it says, draw the structure of the product of hydrolysis of a non-alkylated N-methylmalonic ester. Right. So it's non-alkylated. What we're going to do here is we're going to draw our structure.

We have our benzene ring here. We're going to say that we have connected to a 5-membered ring. Here's the nitrogen here. Now, it's going to be connected to the alpha carbon. And so we have here our ester and here our ester.

That R could be ethyl or it could be another R group. Alright. So what we're going to do next is we're going to do H3O+ and some heat. So remember, what effect is that going to have? That's going to basically change these esters into carboxylic acids.

And then we're cutting this out here, excising it out, and that's going to be my coordinated amine. And then we use additional heat which is going to cause decarboxylation. So we lose one of these carboxylic acids as CO2. So we have at the end is our protonated amine. It's going to be connected to the same carbon, which is still connected to this carboxylic acid.

Right. So we've made our amino acid, our glycine, our most simplest of amino acids as our final product. Right. So this is the process we would do in order to get the product from the hydrolysis of our non-alkylated N-methylmalonic ester.

Synthesis of Amino Acids: N-Phthalimidomalonic Ester Synthesis Concept 2

Ampithalamidomelonic ester synthesis uses simpler starting materials than the acetomito malonic or malic ester synthesis. Now, we're going to say the amino group comes from the nitrogen atom of the pethylamide molecule. And we're going to say here that the base skeleton or the base carbon skeleton of the amino acid comes from the alpha-bromomelanic ester. And then finally, the side chain comes from an alkyl halide. So if we take a look here, here is our alkylated amino acid or amino acid in general.

So let's break this down retrosynthetically. We're going backwards here. We first cleave off this from the alpha carbon. And what we have here is our regular glycine here. We have our amino group.

We have a carboxylic acid, they're connected to this alpha carbon. If we go further and cut it here, the nitrogen that got cut off was part of the pethalamide molecule. So here it is right here. And then this alpha carbon and this carboxylic acid group was originally part of this, our malonic ester. And we're going to say here we see that the alpha carbon has a bromine on it.

And then this group here in pink or magenta that we cut off in the beginning, this was originally our alkyl halide. So, again, the way you can look at this is we have our alkyl halide, we have our methylamide molecule, and then we have our halogenated malonic ester. These components together are what we used to create this amino acid by way of our pathalmetomelonic ester synthesis.

Synthesis of Amino Acids: N-Phthalimidomalonic Ester Synthesis Example 2

In this example question, it suggests using an alkyl halide to synthesize histidine using the N-bethylamidomelanic ester synthesis. Alright. So let's draw out what histidine resembles. Here we're going to have our cyclic structure which has our nitrogen embedded within it. So we have NH here and then we have another pi bond here.

Oops. That goes right there. Actually, so there goes my 5-membered ring. And then it's going to be connected to this carbon here, which is then connected to an alpha carbon connected to an NH₂ group. And we have our carboxylic acid here.

Alright. So we have our carboxylic acid portion right here, which is part of the alpha carbon. This part came from our malonic ester. We have our amino group, which was part of the Bbethelimide molecule. And then we have the rest of this which was part of our alkyl halide.

Now we want to see what the alkyl halide was. All you have to do is cleave this portion right here. And looking back retrosynthetically, all we do now is redraw this again. Okay. Five-membered ring connected to this. And when we cut, we're just going to add a halogen there.

So this was our alkyl halide that we used in the beginning. So again, for this particular synthesis, look at your histidine, mark the portion that is the amino group that came from the Bbethylimide molecule, mark the portion that's the alpha carbon and the carboxylic acid group, that came from your malonic ester. The rest of it, the side chain came from an alkyl halide. So all you have to do is add a halogen to where you cut it. We cut it right here.

So you just have to add a halogen to that carbon, and you'll have your alkyl halide that you started with. Right? So that's the process you need to employ in order to get to your final answer.