Sciencemadness Discussion Board

Benzoquinone from Paracetamol

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JJay - 5-2-2017 at 11:45

That makes sense. I'll use sulfuric acid for neutralization, and I'll let you know how it goes.

JnPS - 5-2-2017 at 12:19

I'm still interested in doing this but with the new semester in full swing I haven't had much time in the lab, you're switching to dichromate as an oxidant but could I still use KMnO4? The problems with your earlier proposed procedure wasn't the choice of oxidant and I have an excess amount of KMnO4 but I only have a small amount of dichromate on hand. If you have any success I'll definitely make time to repeat the experiment. Just to double check the new proposed procedure is :

1. Base hydrolysis of paracetamol loosely following chemplayer's video but barring the purification step to avoid product degradation
2. Use crude aminophenol in oxidation to benzoquinone using respective stoichiometric amount of oxidant

JJay - 5-2-2017 at 12:39

I think it's possible to do the oxidation with permanganate, but the OrgSyn article above states reaction conditions and yields for dichromate, and finding those with permanganate will likely take some experimentation. I think permanganate is a somewhat stronger oxidizer than dichromate. I haven't closely checked the stoichiometry of the OrgSyn procedure, but I plan to use something pretty close to the ratios that they recommend... I would think they would be stoichiometric.

It's going to be harder to nail the exact amount of oxidizer to use when using an impure reactant, of course... I'm tentatively leaning towards keeping the same ratios as the OrgSyn researchers and expecting slightly lower yields.

JJay - 5-2-2017 at 20:30

I am attempting to de-acetylate now. 7.23 grams acetaminophen, 5.85 grams NaOH, 35 ml water on a water bath with stirring with a Vigreux column as condenser

IMG_20170205_192636.jpg - 393kB

Edit: If you try this, I would suggest filtering the mixture through paper. I used a frit and it was horrible to clean... methanol and water didn't seem to help much, but vinegar cleared out most of the gunk, and then concentrated bleach took out the brown color.

[Edited on 6-2-2017 by JJay]

JJay - 5-2-2017 at 22:31

7.23 grams acetaminophen was measured out. The chemist noticed that the acetaminophen, formerly a light pink color, had turned mostly brown and smelled moldy after sitting for a couple of weeks. 5.85 grams NaOH was weighed and added to 35 ml water in a 100 mL flask on a water bath with stirring. After it had dissolved, the acetaminophen was unceremoniously dumped in, and the flask was fitted with a Vigreux column to serve as a low-capacity reflux condenser. The water bath was brought to boiling and kept there for 1h.

The dark brown reaction mixture was removed from heat and filtered while still hot, leaving behind some chunks and goo that were difficult to clean from the frit. The intensely dark brown filtrate was then neutralized with 5.5 mL of concentrated sulfuric acid, which reacted vigorously when added dropwise to the still-warm solution. Wearing goggles is highly recommended. After all the sulfuric acid had been added, the pH was very slightly acidic.

The chemist was pleased to see that some precipitate was visible in the still-warm flask, which was set aside and allowed to cool.

[Edited on 6-2-2017 by JJay]

JJay - 6-2-2017 at 00:12

Ugh... I looked at the flask a few times, and it appeared to me that there was less precipitate than I had noticed previously. I thought that was odd... so anyway, I watched Nile Red's workup of p-aminophenol, and he thought that decomposition significantly impacted his yields, so I figured I should do the workup right away. I quickly vacuum filtered and barely got anything... just .11 grams of a dark brown powder.

JJay - 3-3-2017 at 14:25

I'm going to attempt this again. I don't think acetaminophen is very soluble in aqueous sulfuric acid, but I think it will slowly dissolve as it is de-acetylated under reflux with stirring, and p-aminophenol should be reasonably stable in sulfuric acid. Once everything dissolves, I will hopefully successfully oxidize the p-aminophenol by adding dichromate solution and proceeding as in the orgsyn article.

It would be nice to use peroxide, hypochlorite, permanganate, or some other more easily accessible and less toxic oxidizer....

[Edited on 3-3-2017 by JJay]

Attempted benzoquinone synthesis by tandem sulfuric acid hydrolysis and MnO2 oxidation

Lex - 4-2-2019 at 22:07

I've just attempted to make benzoquinone from acetaminophen by first deacetylating with H2SO4, and then stirring the 4-aminophenol produced (likely present as a bisulfate salt) with manganese dioxide powder. I think this may have worked, but I've run into a lot of trouble with the work up: I tried extracting whatever the product is into ethyl acetate, and then tried to distill the ester off, but the distillation seemed to bump excessively, even with vigorous stirring, so I've put it aside after a rather alarming boiling-over. Anyway, I'll go into my process in case it is of use to anyone or if anyone has pointers.


Acetaminophen was extracted from 20 g worth of paracetamol tablets by covering them in around 150 mL of acetone and boiling and stirring until the pills had disintegrated. The mixture was filtered hot, and the acetone was distilled off of the acetaminophen in a 500 mL rb flask. 19.5 g of largely dry, but quite pink acetaminophen was obtained.


~80 mL of 50% H2SO4 (w/w) was charged into the same 500 mL flask, on top of the acetaminophen, and the flask was set up for distillation. The liquid temperature was held at about 120 ºC (above the bp of acetic acid), and the distillation was continued until the drip-rate slowed.

About 40 mL of distillate was collected, and given the theoretical amount of AcOH hydrolysed and distilled should be 7.75 g or so, a lot of this will be water. The clear, slightly syrupy distillate had a pH of ~3-4 (my pH paper isn't much good), a density of around 1 gcm-3. It smelt like AcOH (but there was another scent to it too - something more burnt smelling), and attacked the nose in the same way. It fizzed with Na2CO3, and make a characteristic blue copper acetate solution with some basic copper carbonate I happened to have handy.

I never actually isolated the 4-aminophenol product, as I was slightly worried about decomposition, and wanted to minimise loses and labour - instead I left it in the flask overnight ready for oxidation. However this hydrolysis seems to have been successful judging by the distillate characteristics. Not even close to a rigorous proof, I know, but there you go! Note that a pretty crystalline mass appeared in the flask on cooling - I suspect this is the bisulfate salt of the product.


This procedure was losely based on the attached articles

34 g (3 eq.s based on starting acetaminophen) of MnO2 powder (obtained as a by-product of KMnO4 oxidation of toluene, dry but otherwise untreated) was added to the rb flask along with 150 mL of water. This was "stirred" while being cooled in a CaCl2 ice bath. I had hoped to keep the temperature below 10 ºC, but the temperature rose fairly rapidly but did not get above 40 ºC. I don't really know if temperature control is imperative, but i suggest adding the MnO2 slowly in order to manage what is obviously an exothermic interaction. There was also a lot of foaming, and my stirrer bar quickly became useless. I had to swirl the flask by hand occasionally. After 30 mins of this, the reaction mixture was worked-up.


This is where I ran into trouble.

The flask contents were filtered, and the flask and filter cake were washed with 3x 50 mL of EtOAc. Things seemed to be going well - where the solution had dried around the sides of the buchner flask, yellow crystals were forming. The ester layer (dark red) was shaken with and then separated from the aqueous (which proceeded fine), but when the ester layer was washed with sat. Na2CO3, I ended up with a nasty emulsion. To make matters worse, the contents had turned black, and it was very difficult to tell if an ester/water interface was forming at all. I tried to break the emulsion with sat. NaCl solution, which might have worked, and I drained what was possibly the ester solution (now jet black) into a 250 rb flask and attempted to carefully distill off the EtOAc.

With strong stirring, the flask appeared to be at a nice rolling boil, but suddenly the thermometer well popped out when the solution "bumped". Stupidly I put it back in and continued trying to boil down the solution. Again, the boiling looked stable, but then suddenly "bumped" again - this time spraying black goo everywhere and popping the distillation rig apart. I now have a lot of cleaning up to do.

I'm unsure what went wrong here. There was obviously some pressure build-up in the flask, but what caused it is unclear. It's possible it was caused by crystals of benzoquinone forming between the thermometer-well and distillation head, which blocked the exit of the flask. It's also possible that there was some sort of exothermic reaction between benzoquinone and an impurity, or the ester itself?

I think this process might be viable though - there are beautiful yellow glints of crystals in the patches of split mixture as the EtOAc evaporates - mocking me. I will have to try again to confirm this route, but if anyone else wants to try it - please let me know how it goes!

Does anyone have any ideas as to what led to the pressure build-up, or any ideas around optimising this process generally?

Hope this thread isn't permanently dead!

Attachment: Newer aminophenol oxidation paper.pdf (626kB)
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Attachment: Older aminophenol oxidation paper.pdf (426kB)
This file has been downloaded 42 times

[Edited on 5-2-2019 by Lex]

nitro-genes - 5-2-2019 at 14:08

Not of much help, though since you started with 80 ml 50% sulfuric, and collected about 40 ml distilate, the sulfuric left in the flask would be around 67-70%, which is enough maybe for sulfonation to occur as well. Maybe reflux conditions would do better? Did you smell any SO2 during the deacetylation?

Would be interesting to know actually what is the end product of heating acetaminophenol with dilute sulfuric. Performed quite a similar reaction (though at 0.5 g scale) as you described once. Also used minimal 50% sulfuric (just enough to dissolve) and kept at 100-120 C for several hours, quite some water and acetic was evaporated off and after several hours, quite suddenly, a white compound started to rapidly precipitate from the solution, until it became almost solid. When reacted with nitrous acid at 0 deg C, it formed a bright yellow compound IIRC, barely soluble in water. It was somewhat recognizable that it was just the slightest bit more energetic and could only just sustain deflageration upon ignition. Upon burning it produced a very strong smell of SO2. Didn't do any further characterization of the compound, and not sure if a bisulfate salt of 4-diazophenol would immediately dissociate in water, though my guess would be that the compound from boiling acetaminophenol with 50-70% sulfuric contains a free amine and sulfonic acid/sulfone group at least.

[Edited on 6-2-2019 by nitro-genes]

Lex - 5-2-2019 at 16:53

Thanks nitro, sulfonation is an interesting thought! Should have taken a sample of the hydrolysis product (my spatula was in the flask with one of the crystals on it, but for some reason I just decided not to bother!).

When I do this again I might reflux, as you say, and then dump in a bit more water and continue the reflux for another 20 mins to make sure sulfonation is reversed in the dilute acid.

Now that you mention it, I suppose the distillate did smell faintly of SO2, and now that I think of it, I'd be very surprised if some of the electron-rich aminophenol wasn't oxidised by H2SO4! I might try bubbling the gases from out of the reflux condenser into KMnO4 solution.

I'd also be very interested in what the gas that caused the foaming on MnO2 addition was. I suspect N2, from the amino groups, but that's just a hunch.

I think that the black tar that made the work-up difficult was polymerised product now, and I reckon the aqueous alkaline wash might have initiated it!

I notice that the older paper I attached above (vacuum) steam distills the quinone out of the reaction mixture, rather than extracting first. This might be a goer if I can set up a viable steam distilling rig.

draculic acid69 - 5-2-2019 at 23:38

If the paracetamol sits in water for too long it turns brown and starts to decompose.even after extracting and recrystallising if it is a little bit wet after a week or two it will turn brown.i suspect it needs to be vacuum dried at a low or room temperature to avoid this if it isn't going to be used right away.

Tsjerk - 6-2-2019 at 09:40

Phenols are easily sulfonated, and sulfonated phenols are prone to addition of nucleophiles. I would suggest to go down to at least single digit percentages sulfuric acid for the hydrolysis. With that much water around I can't imaging the hydrolysis to be far from completion once equilibrium is reached.

Wouldn't it be an idea to do this reaction in a closed bottle to keep oxygen out, and then heat it below boiling point on a water bath?

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