[Rishi]

Can anyone please highlight the process for synthesis of 3,4-Dihydroxybenzaldehyde (Protocatechualdehyde)? And especially if the process involves the bromination of 4-Hydroxybenzaldehyde and then the next step leading to the product. I am through with the bromination but couldnt substiture the bromo group with hydroxy group.

Please help at earliest.
With many warm regards

[macman104]

I didn't check to see if there's conflicts, but assuming the reaction will go forward without reacting some other way, you can take your brominated product, put it in NaI and Acetone, then you can react it with AgNO₃ and Acetone-Water solution, to form replace the I with an OH group.

[proufs]

Alternatively you may consider looking at this link and the citations therein:

http://orgsyn.org/orgsyn/default.asp?formgroup=basenpe_form_group&dataaction=db&dbname=orgsyn

[Rishi]

Well, I did take a look and tried it. But somehow doesnt work out in the costing. I read many references from Chem. Abstracts. The two most effective methods are from Mandelic acid and o-hyrdoquinone. Again 0-hydroquinone gives mixed isomers. And the products being solids pose difficulties in separation. So have to overlook that route.

Macman, the route you suggested makes use of iodine and AgNO3 which drives the costing through the roof.

[russellm72]

Is this not commercially available at a much reduced price from how you could make it in house. This of course depends if your in an academic or pharmaceutical enviroment...

Regards

R.

[Rishi]

Russell...I work in an industry and am looking out for commerically viable option.

[russellm72]

Ok so what do you want to start with? any ideas

R.

[Rishi]

Either I have to synthesize the mandelic acid and hydrolize it or the second rout is to brominate p-hydroxy benzaldehyde and then hydroxylate the resulting 3-bromo-4-hydroxybenzaldehyde. And right now, I am not getting good yields in this hydroxylation process. Hence i was confused.

[Dynamic]

Why don't you start with vanillin?

[Rishi]

If i start with vanillin, i need to use HBr to hydrolyse the -OCH₃. I tried and couldnt get good conversion. Got about 80% conversion. Then it becomes difficult to separate Vanillin and 3,4-Dihydroxybenzaldehyde.
Could you tell a better option to hydrolyse the -OCH₃ ?

[alphahydroxy]

Had a quick look, amd according to patent: DE 269544, 3-bromo-4-hydroxy-benzaldehyde and be converted to the dihydroxy compound using NaOH and CuBr...


Didn't look at closely at all though, so not sure how effective this is, or whether you have tried this already...

[Rishi]

Have tried the process. It involves use of CuBr or CuCl and DMF as solvent. A dirty process. Wouldnt go for it if i get a better alternative.

[Rishi]

Is it possible to demethylate Vannilin to get 3,4-Dihydroxybenzaldehyde ?
What would be a safer choice, aqueous HBr or Sulfuric acid ?

[Fleaker]

Sulfuric acid doesn't work well. HBr works, but you mentioned isolation is difficult (although I'm sure you can figure it out). HI is even better but it's expensive and a regulated chemical. There is also demethylation of vanillin with thiourea and AlCl₃, which is in the 70s yield-wise.

3,4-dihydroxybenzaldehyde is really prone to oxidation, so make sure you attempt this under argon.

Since your interest is industrial, you will likely not want to start from the rather expensive vanillin and go about demethylation.

You'd probably be better served starting from catechol and doing some sort of modified RT to para formylate rather than ortho. It has been done, I know I've seen a paper on it. I don't think yields were horrific, but they weren't amazing either.

Good luck.

[Rishi]

Thanks, Fleaker...Would like to try it out. Could you pass on the paper of the same ?