Doctor Cat
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Question on Friedel-Craft alkylation of Catechol and Dopamine synthesis
My target molecule is dopamine hydrochloride. From a long time I've been wanting to synthesise dopamine just for the fun of it.
I came up with the idea that the easiest pathway is the friedel craft alkylation of catechol with 3-chloro propanamide (made from a 3-chloropropanoic
acid ester and anhydrous ammonia) and then the resulting amide would be reacted with chlorine and sodium hydroxide in a hofmann rearrangement to give
the free dopamine molecule. after that the only thing left would be adjust pH and isolate the hydrochloride salt.
The biggest problem with my process is that I have no reference (I couldn't find any) that the alkylation of catechol is actually posible. I'm
thinking that maybe is a good idea to protect the hydroxyl groups in catechol first...
What are your thoughts on this? any help will be greatly received 
Also, plz forgive me if I am committing an ovbious mistake... I'm not a chemist...
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clearly_not_atara
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Can't you just use acrylamide? The 3-chloro is going to give off HCl easily.
But yes you can do FC rxns on phenols, FC alkylation is acidic, whereas nucleophilic exchange (O-alkylation) happens under basic conditions.
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CuReUS
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Quote: Originally posted by Doctor Cat  |
I came up with the idea that the easiest pathway is the friedel craft alkylation of catechol with 3-chloro propanamide |
FC on phenols is not a good reaction,the lewis acid catalyst will react with the phenolic group rather than forming the electrophile from the
3-chloropropanamide.
I think the best method would be to start with catechol aldehyde and either react it with nitromethane and then reduce it ,or make the corresponding
cinnamic acid derivative,reduce the double bond to get hydrocinnamic acid and then do a hoffman bromamide on that.
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Nicodem
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Thread Moved
10-8-2015 at 09:33 |
Doctor Cat
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I'm thinking in something like this:
1) Perform a Henry reaction on protocatechuic aldehyde with ammonium acetate on GAA to give 4-(2-nitroethenyl)-1,2-benzenediol
2) Reduce the nitro group with SnCl2 / HCl
3) Hydrogenation of the double bond
It seems easy enough!
Now to the long and tedious gathering of the reactants... :/
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Doctor Cat
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I was thinking... would it be possible to perform a FC reaction on 1,4‐benzodioxan or say... 1,2-Dimethoxybenzene?
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byko3y
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Catechol is very prune to oxidation, you need to protect it first. https://commons.wikimedia.org/wiki/File:Dopamine_synthesis.p...
Then I know no easy way to directly add the ethyl group to dialkyl catechol, so you should stick to well known methods (as pointer by Doctor Cat),
until you are ready to perform an extensive analysis of your product.
[Edited on 11-8-2015 by byko3y]
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FriedBrain
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To methylate the OH- Groups of your catechol, you can take a look at the following thread, there is someone looking for safe methylating reagents like monomethyloxalate. You (or your catechol) could serve as there
little guinea pig 
You could give it a try, I would be interested in your results, good luck!
[Edited on 11-8-2015 by FriedBrain]
You always have time to do some chemistry, but maybe you just have other priorities?
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