[allenjw4]

Hello I am currently in Organic 2 and we are starting our Mega project. My group has chosen synthesis of Dopamine. We are starting with catechol and while I have the proposed reaction completed for most of the synthesis I am stuck with one of my intermediates. In this case 3,4-Dihydroxyacetophenone, I am unsure how to deoxygenate the ketone without also removing my alcohol groups. Any help with this directly or pointing me to relevant material would be greatly appreciated.


It might also be that there is a better way to add the carbons to the benzene ring instead of adding Acetyl chloride which is something I am currently looking into.

[allenjw4]

I also revisited one of my proposed reactions that i showed my professor. I realized that I had one of my reactions backwards and that might have been why he didnt think it would work. Would a friedel crafts alkylation using vinyl bromide or bromo ethane with febr3 work on catechol.

[wildfyr]

No, it would not. You can't do friedel-krafts in the presence of labile protons. You can exert some control to by forcing thermodynamically favorable conditions, but your ring will be so activated that you're going to end up polyalkylating the ring, and separation of such materials is a total pain the ass.

I think what you are asking is how to reduce the ketone to an alkane. I think you can find a method on your own if you think of it in terms of reduction chemistry.... but I dont think 4-ethyl catechol will get you very close to your end product.

Catechol is a very difficult substrate to start from frankly. Heck, dopamine is a tough molecule to make non-biogenically period using normal lab conditions. The catechol group has very unique reactivity which is hard to work around. I've thought of a pathway, but I dont like it and its about 4-5 steps

If you want to work with it, you need to look into protecting group chemistry.

PS: Your group is trying to actually make this at the bench right?

[allenjw4]

To be frank we just browsed chemical structures and picked this. I am the only one in the group who can propose any sort of mechanism for our reaction, but i am finding out that dopamine is very hard to synthesize. My professor said it would be cool so I stuck with it. The good news is that we only have to do 2-3 steps of our proposed reaction. From what i currently know now I plan on synthesizing chloroacetyl acid and adding it to the catechol, depending on my research into group protection at your advisement ill see if we can do another step in getting closer to the product.             


So yes we are trying to make it but we know at this point we will only get a few steps in.

[wildfyr]

If I could be so bold, would it be possible to start from at least 1-methyl-3,4-dihydroxy benzene?

[zarhym]

It looks like you don't have enough tools in your tool box.

I'd like to give you some links of reactions you probably do not know.

http://www.organic-chemistry.org/synthesis/
https://faculty.chemistry.harvard.edu/myers/pages/chem-215-handouts

I agree with wildfyr on your friedel-krafts idea. It requires protecting groups to make it work.
And here is the link for protecting groups.

http://www.organic-chemistry.org/protectivegroups/

1-methyl-3,4-dihydroxy benzene is a good starting material.
You can do something with the methyl. 
Hmm, maybe protect the hydroxy groups first and then do something with the methyl group.

[allenjw4]

I've searched our inventory, @wildfyr we do not have that starting material @organicdan96 we do not have that either.  It looks like my best bet at the moment is working on addition chloroacetic acid and working from there.

[wildfyr]

What protecting group chemistries does you stock room give you access to? I can think of 1 (the most useful one for this reaction!) that should be accessible in any stockroom.

[wildfyr]

BabcockHall and I were having a PM discussion and I stumbled across this spectacularly useful reaction for you allen

http://www.prepchem.com/synthesis-of-2-chloro-3%E2%80%B24%E2%80%B2-dihydroxyacetophenone/

I can't justify to myself why it works, but its sure as hell worth a shot because that is the substrate you are aiming for. I'm puzzled by lack of any other reagents.

If you can make this, then getting to dopamine should be possible in a few simple steps.