Sciencemadness Discussion Board - Extraction of Protocatechualdehyde from Conc Sulfuric Acid

Extraction of Protocatechualdehyde from Conc Sulfuric Acid

Lancer85 - 25-9-2024 at 22:17

Ethyl vanillin and a very large molar excess of conc sulfuric acid were heated in a flask and everything dissolved. Yields are supposedly good however after the reaction is done and everything cools down to room temperature, the product stays dissolved in the acid. Now similar reactions to this like producing isovanillin they extract the product in ice water with an organic solvent.

From others i’ve heard they were able to extract half of it while the other half stayed stuck in the sulfuric acid/water layer. Could something be added to the aqueous solution to get more to dissolve in the organic layer? NaCl reacts with sulfuric acid but I don’t know at what concentration. What concentration would it be best to have the acid/water layer? What solvent would be best to use? Ether?

Sulaiman - 25-9-2024 at 22:52

I know very little but in general
If this is prototyping for bulk production then you can investigate many options to get more product into the organic layer,
but if it's a one time experiment I would first extract my nice 50% yield,
then work out how to get more from what remains,
without worrying that in trying to get more I could damage the good 50%.

Lancer85 - 25-9-2024 at 23:32

Quote: Originally posted by Sulaiman

I know very little but in general
If this is prototyping for bulk production then you can investigate many options to get more product into the organic layer,
but if it's a one time experiment I would first extract my nice 50% yield,
then work out how to get more from what remains,
without worrying that in trying to get more I could damage the good 50%.

True but being a perfectionist and not to do things wastefully I want my obtained yield in full.

Niklas - 26-9-2024 at 06:33

Pouring the reaction mixture onto some crushed ice and extracting the resulting strongly acidic solution with an organic solvent should work quite well. DCM, the usual choice for extractions at least for me, quite sucks in this case, tho I‘ve gotten satisfactory results with both ethyl acetate and MTBE.

I recommend not to wash the resulting extracts with brine though (at least in case of MTBE, haven’t checked with ethyl acetate), since for me this surprisingly resulted in a lot of product moving into the aqueous phase. Directly drying it with sodium sulfate or such is more than sufficient.

The protocatechuic aldehyde resulting from all this will most likely be somewhat impure, so you‘ll have to recrystallize it from water afterwards.

Lancer85 - 26-9-2024 at 08:00

Quote: Originally posted by Niklas

Pouring the reaction mixture onto some crushed ice and extracting the resulting strongly acidic solution with an organic solvent should work quite well. DCM, the usual choice for extractions at least for me, quite sucks in this case, tho I‘ve gotten satisfactory results with both ethyl acetate and MTBE.

I recommend not to wash the resulting extracts with brine though (at least in case of MTBE, haven’t checked with ethyl acetate), since for me this surprisingly resulted in a lot of product moving into the aqueous phase. Directly drying it with sodium sulfate or such is more than sufficient.

The protocatechuic aldehyde resulting from all this will most likely be somewhat impure, so you‘ll have to recrystallize it from water afterwards.

What were your yields like? Excluding the time you washes with brine. And what should you aim for in terms of ice water? 20-30% wt acid solution? I’m surprised that you lost some still using brine…

Niklas - 26-9-2024 at 10:19

Quote: Originally posted by Lancer85

I made it by the demethylation approach of vanillin, so the yields are somewhat hard to compare. Tho the idea of the workup is basically the same, just that you have hydrochloric acid as your acid rather than sulfuric. I recall it being above 75% for sure, at least the crude yield (didn’t have to purify for the next step of my synthesis).

The exact quantity of water shouldn’t really matter, just make sure the pH is above 1. I think in my particular case I had something like 3 g of product in around 40 ml of aqueous acid.

And yeah, regarding the brine, it really threw my off as well, I think I may not have acidified it enough that time, but I really don’t know. It shouldn’t happen normally, that’s for sure.

clearly_not_atara - 26-9-2024 at 11:43

If you can extract 50% from the solution the first time, then since partition coefficients are usually constant for stable molecules, you can just repeat the extraction to get the next 25%, then 12%, etc.

However, if the yield is stated as 50%, it is likely that some of the product is decomposing. Multiple extraction is a very common technique in chemistry. People wouldn't just forget.