[Bru]

Hello, everyone! I'm currently taking organic chemistry (nearing the end, woo!). One of our final projects is to do a retrosynthesis of a really big compound, and I'm having immense trouble with mine. The main goal is to disconnect our compound into commercially available compounds with six carbons or less. I talked to my professor and he redirected me to a bunch of websites that ended up just confusing me more. We've only ever done retrosyntheses with like, two parts, never four like this.

This is my compound (sorry I'm not using the structural formula, but it's much easier for me like this):


This is what I've tried so far:



I guess I'm basically asking for help on the retrosynthesis of the two middle pieces (after the first retrosynthesis), or for help in general. Did I break down the target molecule at the right place? I think once I understand what the two middle pieces should be, I can kind of (maybe?) figure out the rest of it.

[kriggy]

some thoughts:
triethylamine is comercialy available, however it wont react with ethanol.
how do you make ester? I think its good idea to disconect there but your "product" is wrong, its and acid and alkane and those dont form esters.
The disconection which leads to triethylamine and ethanol but those two will not form the ether you want. I think you might want to read a bit about reaction of oxirane, more specificaly addition of amines and alcohols
http://en.wikipedia.org/wiki/Ethylene_oxide#Adding_ammonia_and_amines
http://en.wikipedia.org/wiki/Ethylene_oxide#Addition_of_water_and_alcohols
And the last one, when you disconect the benzene ring you get an acid and benzene but those will not form the bond you need. You need to introduce some functional groups which can make this possible. How can you alkylate benzene?

I hope my thoughts will help you

[AlphaScent]

Questions like these are why I love organic chemistry.  There is never one way to a product, especially on paper.  I would go with what kriggy has said.  Great start.  Let us know where you get.

[Bru]

Alright, I alkylated my benzene, but how do I get the carboxylic acid there? I can't use chromic acid because that'll just cause it to add at the benzylic position, right? So I'm really stuck there. (Ignore the fact that the picture cut off the last carbon in the synthesis of the alkyated benzene.)

I'm still completely stuck on the amine and ether group. I don't even know if the part where I broke the target compound is right--will those two react to give me my target compound?

Can I please get more help on the formation of the amine-ether compound?

[kriggy]

I see the same problem as before: by disconecting ester you get carboxylic acid and alcohol.
About the problem with alkylating benzene: Do you realy need to remove the carboxylic group ? Why dont you do FC alkylation with compound already having carboxylic group present?
About the amino-ether part of the molecule: I see you drew some oxirane reactions, can you use them to make the amino-ether chain?
Remember, you dont have to split to the smallest pieces, you can use anything you want, only requirment is that you can buy it somewhere.

[AlphaScent]

let me give you a hint about the Friedel-Crafts alkylation.  You need to alkylate the benzene with the carboxylic acid present.  But you need to have a reactive element alpha to the carboxylic acid.  What sort of molecule can you put alpha to the carboxylic acid that helps with Friedel-Crafts alkylation?? 

[Bru]

That's the problem-- I don't know. I never even learned that I could do FC-alkylation with a carboxylic acid group present. I already have a chlorine alpha to the carboxylic acid, right? I don't think I need anything else in order to make FC-alkylation occur?

If I can use benzene and 2-chlorobutanoic acid to create what I need, then I need to know how to make 2-chlorobutanoic acid. I need to know how to make that because my starting materials have to be 1.) commercially available, 2.) have 6 or fewer carbons, and 3.) can only have one functional group.

[Bru]

edit: Okay, in answer to my own question in creating 2-chlorobutanoic acid, I can use 1,2-butanediol, right?

[kriggy]

How can you be sure that the substitution will be done on the -OH group you want?
I think it might be better to oxidize the diol to keto-acid and then reduce the ketone to alcohol by some mild reduction agent, I think NaBH₄ could work here. Then you can make the ester and convert the hydroxy group to chloro group and do the alkylation.

[Bru]

Ahh, thank you Kriggy! I didn't even think about that (oops). So, I think I have the first part done, seen here:



I'll post again when I work a little bit harder on the other half of the synthesis. I'm sorry you all have to spoonfeed me like this  thank you so much for all your help so far, I don't know how I would do this by myself.

[AlphaScent]

Way too complicated for making an alpha-halo (bromo) carboxylic acid....this is a known reaction.  Also it should be taught in all general organic chemistry courses.

Look up the Hell-Volhard-Zylinsky reaction. 

[Bru]

Thank you, Alpha! I honestly wasn't taught that reaction. That makes things a lot easier.

[kriggy]

Way too complicated for making an alpha-halo (bromo) carboxylic acid....this is a known reaction.  Also it should be taught in all general organic chemistry courses.

Look up the Hell-Volhard-Zylinsky reaction. 

Never heard of it to be honest  . But yeah, now it looks so simple.

@Bru: Im pretty sure you could figure it out by yourself
 

[Bru]

Alright, so, for the left half of the synthesis, this is what I've come up with. I've used reductive amination to get the two ethyl groups. Do I need to be worried about the alcohol also reacting during the amination?



I'm also trying to think of how to get the alcohols to turn into the needed ethers, but give me some more time on that one.

[AlphaScent]

you are going to have to do something to the carboxylic acid to make it more reactive towards alcohols.  what do you think we can do?