Sciencemadness Discussion Board

Synthesis of dopamine from catechol

 Pages:  1  2

clearly_not_atara - 9-11-2017 at 01:18

Yeesh. I knew making BBr3 was hard, but I didn't think it was bromine at 325 C hard.

Pyridinium hydrochloride is reported as an effective demethylating agent. I've always secretly suspected that pyridinium hydrobromide might be even better.

CuReUS is right: unsubstituted o-quinones are unstable. O-quinone undergoes Diels-Alder reactions with itself, forming strange side products.

Melgar - 9-11-2017 at 11:45

If I can do the niacin to pyridine decarboxylation, then I'll look into pyridinium chloride and/or bromide. I think the chloride is because halogen exchange would make the bromide pointless and potentially complicating, since AlCl3 is also present, no?

With the type of videos we want to show, unorthodox routes and reactions that haven't been documented are actually preferred. The idea we want to convey is that you don't need to have a state-of-the-art lab to make new discoveries in science. Like, new scientific discoveries are within reach of anyone of moderate means.

I have boron carbide and bromine, the trouble is finding anything that won't instantly be eaten through by bromine at 325C. Besides boron carbide, apparently. The only way it'd be possible is by sealing it in a glass tube, but the tube would have to be at least 20-30 cm long, so the bromine wouldn't boil away as you melted the glass.

[Edited on 11/9/17 by Melgar]

JJay - 9-11-2017 at 12:17

I don't have any boron carbide....

clearly_not_atara - 9-11-2017 at 13:09

Quote:
I think the chloride is because halogen exchange would make the bromide pointless and potentially complicating, since AlCl3 is also present, no?


No, the reaction uses pyridine hydrochloride alone with strong heating (microwave):

"Basically the microwave demethylation fucking rocks, as far as ease goes, but the downside is because you need 5:1 pyridine HCl:eugenol."
"I made my pyridine HCl by gassing pyridine with anhydrous HCl gas, this was pretty easy (just gassed it for a while, some crystals formed but it was quite hot so i froze it, many more crystals formed, filtered it, washed with ether, then put the crystals on the bench to dry, came back, almost no crystals left and very sloppy, note-they are very deliquescent and they sublime so put them in a closed container immediately post production."
"All I did was added eugenol in the weight ratio five parts pyridine HCl two parts eugenol (this is molar 5:1), put this in a round bottom flask, stoppered it, microwaved in a normal microwave on medium low (the paper uses 215 watt oven) for two minutes, the stuff melts and turns quite hot, it was removed, cooled under the tap until it was room temp again (just felt it with my hand), then microwaved again for two minutes etc etc, this process was repeated six times, the more you do it the hotter it gets each time. After the sixth time i cooled it again, poured some cold water from the fridge into into it and extracted it three times with ether, pooled the ether extracts, removed the ether on the rotavap, the residue had no smell of clove oil whatsoever, just the smokey smell of the demethylated product, so i assumed quantitative yeild cause I couldn't be fucked vac distilling a room temp solid and/or GC'ing it, also the methylation requires an excess of all other reagants anyway."



[Edited on 9-11-2017 by clearly_not_atara]

Melgar - 9-11-2017 at 14:05

Quote: Originally posted by JJay  
I don't have any boron carbide....

Got five bucks?

https://www.ebay.com/i/181516028071

It's also a commonly-used sandblasting grit, so I'd consider it OTC for all practical purposes.

JJay - 9-11-2017 at 14:34

It's about as OTC as iron oxide... but I think you can use boric acid or borax with carbon too.

It looks like higher temperatures reduce the amount of bromine required: https://www.google.com/patents/US2989375

Edit: I should probably point out that I'm having some difficulty finding a credible reference for the temperature of 300 C quoted in various places.

[Edited on 9-11-2017 by JJay]

Melgar - 10-11-2017 at 01:10

Quote: Originally posted by JJay  
It's about as OTC as iron oxide... but I think you can use boric acid or borax with carbon too.

It looks like higher temperatures reduce the amount of bromine required: https://www.google.com/patents/US2989375

Edit: I should probably point out that I'm having some difficulty finding a credible reference for the temperature of 300 C quoted in various places.

[Edited on 9-11-2017 by JJay]

Hmm. What about a fused-quartz reaction area, heated to red hot with a torch, containing boron carbide? Say, a length of tube, bent slightly in the center so the boron carbide stays there. Run bromine through the reaction area in a loop by collecting the distillate in a non-pressure-equalizing funnel, then adjust the flow rate on the funnel to send more bromine through the reaction area? Not sure how to make a fused quartz tube part of a closed loop for bromine distillation, but if that could be solved, it seems straightforward otherwise.

JJay - 10-11-2017 at 11:31

Continuously recycling the bromine in a reasonably-priced setup is going to be tricky.

[Edited on 10-11-2017 by JJay]

Melgar - 10-11-2017 at 11:49

Oh, I just meant use borosilicate for everything except the hottest part where the boron carbide is. It could also be open to the air, via a vigreux column or something, since bromine vapors are easy to see. Really though, I wouldn't bother with that since bromine barely generates any pressure in a closed system, assuming the vapors can easily flow to cooler parts. There needs to be vapor movement though, and what you seem to be suggesting could result in an equilibrium, with very little bromine ever being able to come in contact with the boron carbide.

Boron tribromide has a boiling point of 91C, apparently. Wikipedia is saying it's soluble in ethanol but reacts violently with water. Usually a violent reaction with water implies a somewhat less-violent reaction with ethanol, but perhaps not in this case?

JJay - 10-11-2017 at 13:16

It would be easiest to recycle the bromine manually. But according to that patent, if the temperature is high enough, it will all be consumed.

I would personally not try using a sealed system for 900 C bromine at home except maybe a small sealed test tube, but I'd prefer to have more than a tenth of a gram of boron tribromide to play with. I'd just drop it or boil the vapors through the hot zone and condense them in another part of the apparatus, fractionally distill, and recycle the excess bromine.

Aluminum tribromide looks easier to make than boron tribromide. I wonder if you can make sodium borohydride by reacting boron tribromide and sodium hydride....

wakatutu - 11-11-2017 at 18:17

Since people are asking about it, I have never seen a write up of an amateur successful with producing protocatechualdehyde via ether cleavage. I had read someone post on this site, I think, where the notion of using sulfuric acid to cleave vanillin was dismissed but the same procedure was said to be effective with ethyl vanillin.

I will have to post some lab notes on here when I get back to my home area. But from here, on my phone at work, I can at least say some of the basics about the reaction. I first tried it with my ample supply of vanillin. The idea is to dissolve the aldehyde in sulfuric acid at 0C, then heat the mixture for some time on a steam bath. The work up is to drip the acid solution into ice water, which causes the unreacted vanillin to precipitate, leaving the catechol aldehyde in aqueous solution. The aqueous solution is then extracted with diethyl ether.

This was highly ineffective with vanillin. Yields were there but very very low. Then I bought some ethyl vanillin after several attempts and failures. This substrate was magical for this process. Upon dripping the acid solution into ice water, no precipitate formed. Ether was used to extract, was distilled leaving behind a crystalline solid with a bit of purple tint. The reaction prior to extraction smelled of ether due to dehydration of the formed ethanol.

Further studies in this area led to methylenation with DCM in DMSO which resulted in heliotropin at a yield of 36% on starting protocatechualdehyde. I had wanted to avoid ether but after attempting to use DCM, and being unable to resolve the formed emulsion and finding the same with chloroform and finding alkanes and aromatics to be poor solvents for this, ether turned out to be the easiest solvent to extract this with.

Melgar - 11-11-2017 at 18:51

Quote: Originally posted by wakatutu  
Since people are asking about it, I have never seen a write up of an amateur successful with producing protocatechualdehyde via ether cleavage. I had read someone post on this site, I think, where the notion of using sulfuric acid to cleave vanillin was dismissed but the same procedure was said to be effective with ethyl vanillin.

I will have to post some lab notes on here when I get back to my home area. But from here, on my phone at work, I can at least say some of the basics about the reaction. I first tried it with my ample supply of vanillin. The idea is to dissolve the aldehyde in sulfuric acid at 0C, then heat the mixture for some time on a steam bath. The work up is to drip the acid solution into ice water, which causes the unreacted vanillin to precipitate, leaving the catechol aldehyde in aqueous solution. The aqueous solution is then extracted with diethyl ether.

This was highly ineffective with vanillin. Yields were there but very very low. Then I bought some ethyl vanillin after several attempts and failures. This substrate was magical for this process. Upon dripping the acid solution into ice water, no precipitate formed. Ether was used to extract, was distilled leaving behind a crystalline solid with a bit of purple tint. The reaction prior to extraction smelled of ether due to dehydration of the formed ethanol.

Further studies in this area led to methylenation with DCM in DMSO which resulted in heliotropin at a yield of 36% on starting protocatechualdehyde. I had wanted to avoid ether but after attempting to use DCM, and being unable to resolve the formed emulsion and finding the same with chloroform and finding alkanes and aromatics to be poor solvents for this, ether turned out to be the easiest solvent to extract this with.

Indeed, there seems to be a lot of hinting at the existence of some original "Q document" describing the dealkylation of ethyl vanillin, but I've never been able to find that document. Thanks for adding that additional information, both about the reaction and about the solubility difference that's used for workup.

I'm really looking forward to planning out this video series now. There was another series we were going to do called "how to do chemistry unsafely", where a mannequin with poor impulse control attempts to do chemistry and makes all sorts of common mistakes that blow up in his face, often literally. I thought that would be a lot of fun, but now I'm having trouble deciding. :D

AvBaeyer - 11-11-2017 at 22:12

Isovannilin is synthesized by methylation of ethylvanillin then selective removal f the ethyl group by treatment with sulfuric acid. This has been published at least once in JACS which you will need to look up as I do not have the reference at hand so you will have to look it up. I have not looked specifically for a reference for delkylation of ethylvanillin.

AvB

JJay - 11-11-2017 at 22:48

This looks pretty interesting: http://www.sciencemadness.org/talk/viewthread.php?tid=28035#...

They discovered reaction conditions for preparing 3,4-dihydroxy mandelic acid, which can be oxidized to protocatechualdehyde. They had some issues with singularities and resolved them using partial least squares (I think you'd get the same results with SVD). Their targets were various flavoring compounds, but as we know, protocatechualdehyde is a couple of easy reactions away from dopamine.
 Pages:  1  2