Show how you would use the acetoacetic ester synthesis to make...

Question

Show how you would use the acetoacetic ester synthesis to make the following compounds.

Accepted Answer

All right. Hi, everyone. So this question is asking us to show how the aceto acidic synthesis can be used to produce the compounds given below. And on the screen here are three keys. Now recall first and foremost, right, that the Aceto Acetic estro synthesis is very similar to the meic estro synthesis, except our key or rather our main product here is a ketone. Whereas in the Banic Essy ISIS, it is a carboxylic acid. No, going back to the discussion of our final product, right. In addition to our product being a ketone, it is specifically the substituted derivative of acetone, right. So an oculd derivative of acetone and for the starting material here, what I've dropped on the screen here is ethyl ato acetate which is an aceto acetic ether. So to review the steps of the Aceto acetic synthesis recall that the first step is going to involve the dep protonation of the alpha carbon in between our two carbons. And so that process is going to require a strong base, namely sodium oxide. So after treatment with sodium meth oxide, we get an eel only iron in which the alpha carbon in between the two car bottles of ethyl aceto acetate has a negative charge. So at this point, babe, an additional R group can be introduced using an S and two reaction with an unhindered oy hali. Because the eno laid on here can very easily react with again, an unhindered Ocu Halide in an essence two reaction which results in the attachment of an R group on to the alpha carbon in between our two car bottles here. Now, in order to yield the resulting substituted derivative of ketone, two steps have to occur. First is the acidic hydrolysis of the aceto acetic ether, specifically the O aceto ay ester followed by decarboxylate. So the first step is going to be hydrolysis of the ether in the presence of acid. So that is going to convert are acito acidic ester into an aceto acetic acid, right. So in the case of the starting material that I drew on the screen here, the a Foxy group is going to be converted into a hydroxy group with our our group still attached. So specifically its an all kill aceto acetic acid. Now, the main thing to keep in keep in consideration here is that our resulting product after acidic hydrolysis is in fact a beta keto acid. So because it's a beta keto acid, our final step is going to be decarboxylate in the presence of heat Rachel. As a result, the carboxylic acid group is removed and we are left with are substituted acetone, as well as carbon dioxide, as well as two equivalents of ethanol stemming from the epoxy group of our starting Esther. So it's this framework that we're going to keep in mind here when determining how we can use the aceto acetic synthesis to produce the compounds given on the screen. So if we go ahead and reanalyze the structure of compound A, in addition to the methyl group, what you'll notice is that we have an additional four carbon chain and we actually labeled it in the opposite direction, right? We've got a four carbon chain, but the attachment of the carbon chain to the car bono is inside the carbon chain specifically on position two. Now due to the fact that this alpha carbon here is attaching to two other carbons. What that means is that we have to attach two different R groups. And that's fine considering that this alpha carbon in between our two car bottles actually has two protons that can be removed. So in our first step, right, for compound A here, our objective is to attach, they may actually erase this. Actually, our objective is to attach a one carbon, our group as well as a two carbon art group. And together along with the alpha carbon itself that will produce the four carbon chain that we see in the end product. So let's go ahead and do that and we'll start off with our Aceto Acetic ether and I'm going to actually move this over for the sake of space. So the first step in this process is going to be the detonation of the alpha carbon with sodium meth oxide followed by the addition of our one carbon R group, which I'm going to do using methyl iodide. So that is going to result in a meth group adding on to the alpha carbon in between our carbon. Now to add the second R group, I'm going to repeat this process again. Right? I am going to add sodium oxide once again. But this time because I need two more carbons, I'm going to add ffo iodide instead. And so that is going to attack not only a two carbon chain but a one carbon chain to the out of position, which will then allow me to remove the oxy group and subsequently the carboxylic acid group. So I'm actually going to combine those steps, right. I'm going to go ahead and write acid first followed by heat to showcase that ester hydrolysis and decarboxylate are both taking place. Right. So here is my resulting ketone, but you also have to recall your by-product. So we've also got co two and we have two equivalents of ethanol from the oxy group of our. And now we can go ahead and repeat this process. We're both B and C. So if we go ahead and we scroll upwards to examine the structure of compound B right here, right. We have the same problem as compound A because our alpha position is connecting to two other carpets, which would mean that we would have to add two separate R groups. But we also have to consider that, that the R group itself is actually a ring. So what we can do in this scenario is introduce a die highlight. So we can introduce with a die Halide, which would allow ESSEN two to happen twice, resulting in the formation of a ring. So the die highlight itself if we discount the alpha carbon has to contain the remaining five carbons of the ring. And these additional metal substituents, let's go ahead and do that right. And I'm going to scroll all the way down here like that. So now let's get started, right? And I'm going to start off with my same exact Aceto acetic ether. And now we can go ahead and begin with our Essen two except right, recall that we would need a dial light in order to form the ring that we see. So instead of adding only one equivalent of sodium oxide, I'm actually going to go ahead and add two equivalents of sodium oxide to go ahead and detonate both alpha hydrogens. And then I'm going to go ahead and introduce a five carbon chain like so with my meal substituents in the center, and Bromine Adams on either end because that after two s and two reactions is going to go ahead and create a six member ring like. So heres my six, my ring and here are, are methyl groups. So now we can go ahead and combine acidic hydrolysis and decarboxylate with both HDO plus and heat. So here is my ring, my key to can't forget my methyl substituents. And we've also got some by-product, specifically carbon dioxide and two equivalents of ethanol. So now we can go ahead and finish off with reaction C. So let's scroll up to examine its structure. Now, compound C has a very similar issue to compound B in the sense that we've also got a ring. So if we discount the alpha carbon itself, what we're going to need is a die Halide with the three additional carbons that will make this four member ring. And because it's a four member ring, I know that my hay lights have to be on either end of the carbon chain. So on positions one and three, let's go ahead and do that and I'll be scrolling down all the way down. So here is my aceto acidic Esther and here we can go ahead and actually reference part B because we're using a di Halide, we're once again going to need two equivalents of sodium meth oxide before proceeding to react with our die highlight, which as we said before is going to be a three carbon chain with BROM means on both ends or halogens on both ends. So that will o kate our Esther specifically with a four member ring. And now last but not least, we proceed with hydrolysis using hto plus, followed by decarboxylate with heat to yield or keto with of course are by products. So here's carbon dioxide and two equivalents of ethanol. So at long last, right, we are done with our full solution, we were able to successfully showcase how to use the Aceto Acetic Astro synthesis to produce all three methyl ketones, including scenarios that required the use of di halides and multiple S and two reactions. So with that being said, thank you so very much for watching and I hope you found this helpful.

Show how you would use the acetoacetic ester synthesis to make the following compounds.

Key Concepts

Acetoacetic Ester Synthesis

Nucleophilic Substitution

Decarboxylation

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