A. Show how the amino acid alanine can be synthesized from...

Key Concepts

Hell–Volhard–Zelinsky Reaction

This reaction is used to selectively halogenate the alpha position of carboxylic acids. By treating a carboxylic acid with a halogen in the presence of a phosphorus reagent, the alpha hydrogen is replaced with a halogen atom, creating an alpha-halocarboxylic acid that can be further manipulated through substitution reactions to introduce additional functional groups.

Nucleophilic Substitution on Alpha-Halocarboxylic Acids

Following alpha-halogenation, these activated intermediates can undergo nucleophilic substitution where a nucleophile, such as ammonia, displaces the halide. This process is particularly useful for introducing an amino group at the alpha carbon, forming the backbone of amino acids like alanine.

Gabriel Synthesis

The Gabriel synthesis is a well-known method for preparing primary amines using phthalimide as a masked ammonia equivalent. Phthalimide is deprotonated to form a stabilized anion, which is then alkylated with an appropriate alkyl halide. Subsequent hydrolysis or hydrazinolysis liberates the free amine, making this strategy suitable for constructing amino acid structures.

Malonate Ester Alkylation and Decarboxylation

Malonate ester chemistry involves the alkylation of diethyl malonate derivatives with electrophiles, followed by hydrolysis and decarboxylation to yield substituted acetic acid derivatives. This sequence of reactions allows for the formation of the carbon framework found in amino acids like glycine, showcasing the utility of malonate esters as building blocks in multi-step synthetic routes.

Transcript

00:01 Okay, this problem is asking us to identify the reactants needed to make these products from our starting materials.

00:05 Okay, so first up, we have proponoke acid turning into alanine, in which alonine is an amino acid.

00:11 Okay, so first up, we have my carboxylac acid, and we recognize that we still have that carboxylac acid nature in my product, except for the fact that we have this nh2 attached to my alpha carbon, in which my alpha carbon is right here.

00:23 Okay, so in this chapter, we've talked a lot about alpha carbons, right? we usually have a deprotonation step in order to turn that alpha carbon into either a base or a nucleophile, usually a nucleophile, and then we attack an electrophile.

00:35 Okay, but as we can see, if we're to use a base to take off that, quote -unquote, acidic proton on this alpha -carbon, we would have our corresponding nucleophile.

00:46 But let's just say that we did have an acid base reaction.

00:49 This base, sodium hydroxide, is not going to take off this proton, right? because we have an even more acidic proton.

00:55 It is this one, right? it's called carboxylic acid, not because of this alpha carbon, or sorry, hydrogen, but because of this hydrogen associated with the alcohol.

01:04 Okay, so we know that my base is not going to take off that proton to make that carbon nucleophilic.

01:11 Okay, so what's our other option? either we can make that carbon into a nucleophile some other way, or we can behave it as a electrophile.

01:19 Okay, and our logic behind why we behave it as an electrophile as opposed to a nucleophile is because we have nh2 here.

01:25 Okay, so nh2, that is my substituent attached to my alpha carbon.

01:30 I know that that would have probably originated as an h3, and we know that nh3 is a much better nucleophile than it is an electrophile.

01:37 So i know that this site is probably going to behave as an electrophile.

01:41 Okay, and one way that we can make that alpha carbon, specifically on a carboxyl acid, an electrophile, is by reacting this with the reactants needed for hvz, or helvol hart -izzolensky.

01:52 Okay, so that is pbr3, b .r2.

01:56 In the presence of water.

01:58 And all that does is add a bromine to that alpha carbon.

02:02 And it retains my carboxylacic acid nature.

02:05 So now i'll just have a bromine on that alpha carbon.

02:07 So now we recognize something like an alkali bromide that is usually behaving as an electrophile so that we can have an incoming nucleophile, replace that bromine as an s &2 or perhaps an s &1 reaction.

02:18 So the next step is using nh3 to behave as a nucleophile to replace this bromine.

02:26 Okay, and i would just like to point out, that this is going to take a long time.

02:30 So i'm just going to write down time, right? because nh3 can have a possibility to take off this proton, but if we have a long amount of time, it is going to replace that bromine.

02:41 Okay, so it's specified time.

02:43 Okay, so the very next problem is this one.

02:46 We have the reaction of thalomide with diethyl to bromomalinate, and then that is going to turn into the other amino acid of glycine.

02:53 Okay, so this is actually a relatively complicated reaction, but as we break it down, we'll see that it's not as complicated as the reactions might show.

03:03 Okay, so first off, we have thalamide.

03:05 Okay, so the thing about thalomide is that it is very acidic, right? because first off, we have our alpha carbons here, alpha carbons there, and we also have this nitrogen, even though it's not an alpha carbon, it is in that alpha -like position, right? so let's just call that alpha for now, even though it's not an alpha carbon.

03:21 Okay, so in terms of acidity, we know that these carbons don't have any protons, so those are not considered acidic.

03:29 And then this one, my nitrogen, it does have a proton.

03:32 Okay, so there's a lot of factors contributing to the acidity of this molecule.

03:35 One, we know that carbons with hydrogens are very acidic on the alpha position, but nitrogen is even more election negative than carbon is.

03:43 So that means that any protons associated with that nitrogen are going to be even more acidic than a carbon.

03:47 And to top that off, this nitrogen is sandwiched between these two carbonyles.

03:51 So that makes this hydrogen very acidic.

03:54 Okay, so anytime we see a molecule like this, we know that the first step is probably going to be an acid -based reaction in which we just take that off with something like sodium hydroxide...

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