Sciencemadness Discussion Board

Benzoquinone from Paracetamol

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tupence_hapeny - 3-4-2007 at 08:38

I have recently searched for both hydroquinone and benzoquinone in this country and the OTC sources of these interesting compounds have basically died. Then, when I typed paracetamol and benzoquinone into google I noticed that the toxicity of paracetamol is caused by the conversion of acetaminophen into N-acetyl-p-benzoquinone imine via oxidation.

Therefore my question is, whether it is possible to further oxidise (and cleave) the n-acetyl-imine from the benzoquinone, leaving the benzoquinone to be used (or reduced to the hydroquinone) as and when required?

I have no idea as to whether or not this is possible, I am basically well behind the chemists on this board. My only interest is basically whether it is or is not possible to transform easily available OTC chemicals to their overly restricted kissing cousins, thereby providing an OTC route for the chemically challenged amongst us.

YT2095 - 3-4-2007 at 09:32

I don`t know about the extraction, but find it hard to believe you can`t get Hydroquinone???

have you searched Photography shops and Skin Whiteners for black people?

not_important - 3-4-2007 at 09:46

And how are you proposing to obtain N-acetyl-p-benzoquinone? Popping pain meds isn't useful, 2/3 to 90% is pissed out as glucurosulfates, N-acetyl-p-benzoquinone is a minor metabolite, and if your liver is working is quickly further metabolised.

Extract acetaminophen/paracetamol with boiling water, filtering out the trash. Cool and filter to collect the product. Hydrolyse with 10% H2SO4, 5 minutes in the microwave under an inert atmosphere. Cool, neutralise excess H2SO4, oxidise using a modified version of the sodium chlorate + V2O5 catalyst method, dichromate oxidation, or other method.

[Edited on 4-4-2007 by not_important]

Nicodem - 3-4-2007 at 09:57

Quote:
Originally posted by tupence_hapeny
My only interest is basically whether it is or is not possible to transform easily available OTC chemicals to their overly restricted kissing cousins, thereby providing an OTC route for the chemically challenged amongst us.

Hydroquinone and p-benzoquinone are both way simpler to just buy given that they are completely OTC. Extracting acetaminophen from pills to get enough for an oxidation where the reagents required would be much less OTC, seems to miss your main idea, doesn't it? Perhaps making something that is not OTC form acetaminophen would make sense, but making two widely available chemicals from another available chemical is a bit irrational.

But essentially, yes, you can oxidize acetaminophen to p-benzoquinone.

tupence_hapeny - 4-4-2007 at 01:36

Ummm, I didn't say I couldn't get hydro/benzoquinone, it's just that what I can get is way overpriced, seriously impure and a minor constituent part of the products I can get. As I am not a great fan of extraction from expensive substances where it is possible to synthesise the same compound from purely otc products - in what hopefully would be a decent yield - I would prefer to go that way. I have been unable to find a single source in Australia that is willing to provide even a miniscule quantity of pure hydro/benzoquinone, whereas I have access to some basic oxidants and shitloads of paracetamol (which is a major part of the tablets - 500mg).

So, taking it as accepted fact, I am actually irrational, how should one proceed if one wished to do so?;)

not_important - 4-4-2007 at 01:44

2.5 cents - already gave a thumbnail outline.

tupence_hapeny - 4-4-2007 at 02:01

oops, half asleep:(

PlatinumCal99 - 4-4-2007 at 10:40

Here in the US it is possible to get hydroquinone but not para-benzoquinone.
One synthesis I was reading involved oxidizing the hydroquinone to para-benzoquinone with chromium trioxide in acetic acid.
Does anyone know what the mechanism of this reaction is? Does the chromium trioxide just form chromic acid and decompose back to chromium trioxide and H2?
If someone with a greater understanding can post back that would be great.

PainKilla - 4-4-2007 at 11:17

http://www.erowid.org/archive/rhodium/chemistry/benzoquinone...

I2/H2O2 in water works wonders.

not_important - 4-4-2007 at 11:46

Quote:
Originally posted by PlatinumCal99...
One synthesis I was reading involved oxidizing the hydroquinone to para-benzoquinone with chromium trioxide in acetic acid.
Does anyone know what the mechanism of this reaction is? Does the chromium trioxide just form chromic acid and decompose back to chromium trioxide and H2?
If someone with a greater understanding can post back that would be great.


Uh - a strong oxidiser forming H2 and not being consumed? I'd sue my inorganic chem teacher if I were you.

The Cr(VI) gets reduced to Cr(III), just like in dichromate reactions.

benzylchloride1 - 8-2-2009 at 22:20

In an attempt to alter the synthesis of p-chloranil from p-acetamidophenol, I ended up producing p-benzoquinone in a yield of 80%. I was trying to conserve nitric acid and see what effect low reaction temperatures has on this oxidation reaction. I started with p-acetamidophenol recrystallized from tylenol tablets, dissolved 15g of the recrystallized material in 100 mL of concentrated hydrochloric acid and then I added 33 mL of concentrated nitric acid. The foam produced by the reaction filled a 1000 mL beaker. The mixture was stirred with a glass rod and allowed to sit in a snow drift for 3 hours. Yellow crystals of the crude quinone formed. 300 mL of cold water was added with stirring and the mixture was filtered. The filter cake was pressed to remove excess water and the benzoquinone was dissolved in about 200 mL of 91% 2-propanol. The solution was heated to boiling and allowed to cool. Yellow, needle shaped crystals of p-benzoquinone filled the liquid upon cooling. The crystals were filtered off, pressed and allowed to dry for one day. The final percentage yield was 80% of theoretical. The melting point was taken with a Haake-Buchler melting point apparatus, the product melted at 117 celsius one degree above the value in the CRC Handbook of Organic Compound Identification, due to a fairly rapid heating rate. The benzoquinone was instantly decolorized by bisulfite solution, and when added to a solution of hydroquinone, peacock green crystals of quinhydrone formed. I plan on making some chloranil in the near future for dehydrogenation reactions. The oxidation of aromatic compounds with aqua regia could be a very useful method for the synthetic amateur chemist.

IPN - 3-2-2010 at 13:45

I gave the aqua regia oxidation a go after the results from a dichromate/sulfuric acid oxidation of paracetamol to quinone weren't very satisfying.

Using pretty much the same amounts of reagents as benzylchloride1 I added 15g of pure paracetamol to 100ml of concentrated hydrochloric acid (new bottle so should be close to 37%). This was stirred overnight (accidentally, I kind of forgot about it while doing other stuff..) and formed a slurry of white fine precipitate. The slurry was cooled outside for approximately 1h (-5C outside) and poured into a 2l beaker. 40ml of 13.5M nitric acid was added in one go with some swirling. This caused the slurry to turn yellow. The color quickly deepened and turned more orange and suddenly the slurry changed to a paste and a vigorous reaction ensued which filled the beaker half full with foam and released a cloud of nitrogen oxides. The beaker was then left in the snow outside for a few hours.
The foam was diluted with around 1/4l of water and stirred for a few minutes while setting up the vacuum filtration equipment. The product was filtered and washed with a few ml of water on a glass frit funnel. It looked almost like picric acid, maybe a little lighter yellow. After being sucked dry for 5min or so it was dissolved in 200ml boiling isopropyl alcohol with 10% water (that is 180ml dry IPA + 20ml H2O) and left to crystallize after full dissolution.
The recrystallized product was filtered with suction and washed with 20ml cold 50/50 IPA/water.

Few pictures of the product can be found here.

So this certainly seems like a good method to make some quinone if you don't need much of it and can't find hydroquinone anywhere. Just be wary of the toxic nitrogen oxides! :)

un0me2 - 3-2-2010 at 23:08

Hypochlorite with acetaminophen/tylenol/paracetamol/etc. gives a combination of the hydroquinoe the the related imine, which would probably give good yields of the sought after hydroquinone on acid hydrolysis.

[Edited on 4-2-2010 by un0me2]

Attachment: Bedner.MacCrehan.Transformation.Acetaminophen.Hypochlorite.pdf (135kB)
This file has been downloaded 1903 times


UnintentionalChaos - 3-2-2010 at 23:25

Quote: Originally posted by IPN  
I gave the aqua regia oxidation a go after the results from a dichromate/sulfuric acid oxidation of paracetamol to quinone weren't very satisfying.

Using pretty much the same amounts of reagents as benzylchloride1 I added 15g of pure paracetamol to 100ml of concentrated hydrochloric acid (new bottle so should be close to 37%). This was stirred overnight (accidentally, I kind of forgot about it while doing other stuff..) and formed a slurry of white fine precipitate. The slurry was cooled outside for approximately 1h (-5C outside) and poured into a 2l beaker. 40ml of 13.5M nitric acid was added in one go with some swirling. This caused the slurry to turn yellow. The color quickly deepened and turned more orange and suddenly the slurry changed to a paste and a vigorous reaction ensued which filled the beaker half full with foam and released a cloud of nitrogen oxides. The beaker was then left in the snow outside for a few hours.
The foam was diluted with around 1/4l of water and stirred for a few minutes while setting up the vacuum filtration equipment. The product was filtered and washed with a few ml of water on a glass frit funnel. It looked almost like picric acid, maybe a little lighter yellow. After being sucked dry for 5min or so it was dissolved in 200ml boiling isopropyl alcohol with 10% water (that is 180ml dry IPA + 20ml H2O) and left to crystallize after full dissolution.
The recrystallized product was filtered with suction and washed with 20ml cold 50/50 IPA/water.

Few pictures of the product can be found here.

So this certainly seems like a good method to make some quinone if you don't need much of it and can't find hydroquinone anywhere. Just be wary of the toxic nitrogen oxides! :)


Get a melting point on your material. I tried this and found that overheating did manage to contaminate the p-benzoquinone with chloranil, even after recrystallization. My melting point was 10 degrees too low.

Taoiseach - 4-2-2010 at 02:02

http://www.versuchschemie.de/topic,13634,-Synthese+von+p-Ben...


User - 4-2-2010 at 05:17

For the people that have a hard time reading german.

http://translate.google.nl/translate?js=y&prev=_t&hl...

Nice write up, i like the use of otc sources.
I feel some resistance here and there but it is no better or worse than TNP from asprin :)

mr.crow - 4-2-2010 at 11:01

Quote: Originally posted by Taoiseach  
http://www.versuchschemie.de/topic,13634,-Synthese+von+p-Ben...



I love versuchschemie :)

They mentioned nitrate salts. That would be easier to get and maybe a less vigorous reaction.

No one has addressed the catalytic I2 route yet. Its probably not a powerful enough oxidizer for the nitrogen.

potassium dichromate

xwinorb - 4-2-2010 at 11:55

I have before made p-benzoquinone using the SpiceBoy recipe, see reference given by Painkilla in this same thread.


You need hydroquinone, sulfuric acid and potassium dichromate, all very easy to get and unexpensive. The reaction is easy and fast, done in 2 h or so. Sodium dichromate can be used also. Don't need to dissolve all the potassium dichromate, it will not. Just drip it in anyway.


Workup, cool it to 5 deg C or close. Filter, if too wet use Saran Wrap when filtering, or squeeze filter cake with a spoon. You will get a dark green solid paste. Filter it as dry as you can.


Can use as it is, just dry it a few days in a closed container or vacuum dessicator with drierite or any other dessicant. It has a substantial ammount of water and other impurities, but for most purposes it works fine. Yield is tipically 60 % or close to that. I mean here, pure p-benzoquinone yield. Just by weight you might have close to 100 % or even higher, but remember it is not pure p-benzoquinone. Also, the impure p-benzo is water soluble.

Assume your yield to be 60 %, calculate how much p-benzoquinone is in and scale accordingly.


If you want purer p-benzoquinone, dissolve it in the minimum ammount of DCM, filter.

You will get a thin layer of green-black solid in the filter cake, and the filtrate has two layers. The bottom layer is DCM + p-benzo ( orange color ), and the top layer is watery, almost black. Separate, keep the bottom layer.

Place in a large boiling flask, boil out the DCM first at RT then with aspirator vacuum.

Evaporate the DCM. It wil start to boil at a higher temperature than the DCM boiling point, you will need aspirator vacuum or similar.

Apply vacuum gently first, then increase. When it becomes a orange paste, bubbling, stop, pour out of boiling flask into a pyrex dish or other shallow container.

Mix with a spoon till most of the DCM evaporates. Better if you have a fume hood, but can be done without it.
It will look orange first, but will become yellow as soon as the DCM evaporates out.

You will haver nice, yellow p-benzoquinone xtals, with just a hint of green color.

The work up is from the Organic Synthesis. They use benzene. I have tried it also, but DCM is much better. Slightly modified.

If you want really pure p-benzoquinone, then from here sublimate or steam distill. I have never done it though.

The non-purified, dark green stuff works fine for most purposes. Dry it well before using.

Suggested to use gloves, handle and pour it carefully, avoid spilling.

Taoiseach - 4-2-2010 at 14:58

Quote: Originally posted by mr.crow  
Quote: Originally posted by Taoiseach  
http://www.versuchschemie.de/topic,13634,-Synthese+von+p-Ben...



I love versuchschemie :)

They mentioned nitrate salts. That would be easier to get and maybe a less vigorous reaction.


No it is very vigorous. I tried it with ammonium nitrate instead of HNO3. Its an amazing reaction - at first the mixture doesn't do anything but all of a sudden it foams up like crazy and gives off thick fumes of nitric oxides. Cooling is crucial to avoid chlorination, which leads to a product contaminated with chloranil.

jwarr - 13-2-2010 at 10:26

I don't understand why anyone fools around with this junk when you can easily prepare p-Benzoquinone from hydroquinone in quantitative yields via catalytic reduction w/ NO2. Hell, if you don't like using gases just use sodium nitrite w/ a drop of HCl.

IPN - 13-2-2010 at 10:39

Well if you would have read the thread you would know that for some, hydroquinone is not that easily available so other ways of synthesis are needed.
And also if only small amounts are needed, what is the problem with this synthesis?

jwarr - 13-2-2010 at 10:42

"Unique Photo" sells 500g of hydroquinone for 15.62 USD, they ship internationally. What is the problem?

mfilip62 - 29-6-2010 at 08:26

Yes in USA,and shipping is ten times the price + no way it can be imported for hobby chemist.
Even Kodak branch here doesn't sell it!

watson.fawkes - 29-6-2010 at 17:11

Quote: Originally posted by mfilip62  
Yes in USA,and shipping is ten times the price + no way it can be imported for hobby chemist.
Even Kodak branch here doesn't sell it!
"No way" is a relative term, given the plentiful existence of black markets and smuggling. Assuming you want a rather more legitimate route, you'll have to state what jurisdiction you're in so that somebody with experience can help you.

mfilip62 - 3-7-2010 at 05:12

HNO3/HCl method seem to be good and working,but only issued being contamination with chloranil...

IS there way to completely remove chloranil,convert it to p-beznoquinone or is there some similar reaction
(HNO3/any other acid for instance) that can produce p-benzoquinone from paracetamol without chloranil contamination
which is too similar in properties and apperance thus making it hard to get rid of and keep the yield!?

un0me2 - 4-7-2010 at 21:09

Mate, I am NOT GOING TO IMPORT ANY CHEMICALS - I have been busted going the import route, I was doing nothing wrong, but it took me months to sort that shit out. I still don't have any chance of getting my glass/chemicals/laptop/pc back...

Good luck if you import to this Cunt Tree:mad:

However, back on subject, from what I can see (There is at least one reference on its use on methoxyanilines) Fremy's Salt will do the job.

There is a great writeup on Orgsyn where it is prepared from sodium nitrite, SO2, sodium carbonate and electrolysis with a Stainless electrode.

That should allow for the preparation of p-methoxyphenol from p-methoxyaniline (2 min MW/HCl will remove the AcOH group from the amine according to at least one report). Methylation, followed by hydrolysis & oxidation of the p-methoxyaniline to the p-methoxyphenol is the ONLY route I know of that will give solely the monomethoxyhydroquinone.:cool:

[Edited on 5-7-2010 by un0me2]

[Edited on 5-7-2010 by un0me2]

JohnWW - 5-7-2010 at 00:49

What jurisdiction do you live in, Unome2? If I were you, I would be looking at emigrating to a less Fa$cist country or $tate.

peach - 8-7-2010 at 09:22

do you specifically need hydro / benzo unome? how much are you talking about?

are you trying to make a ketone?

[Edited on 8-7-2010 by peach]

mfilip62 - 8-7-2010 at 09:58

Hydro/benzo are great as selective oxidants.
I used them a lot in peroxide research, just when I started to do some research on
HMDT analogues they became banned and extremely hard to find.
That is because retarded people used them as "wonder medicine" a lot and irresponsibly for
minor skin imperfections causing cancer, mutilations...
IMHO that is just evolution working, let the bastards die instead of banning something useful!!:P
Anyway, photographers got pissed and now it is good business selling this stuff!

Ketone is pretty wide deffinition, you mean THE ketone from THE olefin or!?
I am not very familiar with that kind of chemistry but I am sure it could be used for that,
but as long as I remember this procedure uses some
H2O2 and formic/acetic acid, at least procedure I read about...don't take me by the word!

peach - 8-7-2010 at 10:13

I'm reasonably sure benzo / hydro became a problem because drug labs were all using it in their wackers; after reading certain google searches.

The wacker / peracid / oxidizing salt / halide + base method will work for a huge number of ketones. You don't need to use benzo for a wacker to make a ketone. Some of them use O2. Anything that'll supply an oxidative potential to the CuCl2 / PdCl2 will work. There are a huge number of ways to a ketone; contrary to your suggestion.

[Edited on 8-7-2010 by peach]

mfilip62 - 9-7-2010 at 14:17

As I said I am not very fammiliar with that field of chemistry.
Just read some searches on that synth.,looks interesting and plausible but
salt formation seems to be waste of time and product.
You think that bubbling O2 instead of using p-benzo in this report would
work?(just google it,it is star something synth.)

un0me2 - 9-7-2010 at 16:54

I just had a good look around and found some interesting procedures, most of which use only fairly innocuous, easily sourced chemicals, to give us a possible route at 2-nitro-4-methoxyaniline, which according to the people here is fairly simply made, although their yields are not stated. That set me looking further, which led me to this paper (attached) which states that extremely good yields can be had by adding H2O2 along with the nitrite/HCl to affect the nitration.

From there, I was looking at a link Nicodem provided for the diazotization of m-Nitroaniline to m-nitrophenol and wondering, could we use that to end up with 2-methoxy-5-hydroxynitrobenzene?

If so, that would open up a whole new route to the 2C series that is so beloved of so many without any majorly difficult-to-acquire chemicals.

Attachment: Matsuno.etal.A.New.Nitration.Product.3NO2.4Acetamidophenol.Obtained.from.Acetamidophen.with.Nitrous.Acid.pdf (143kB)
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mfilip62 - 15-7-2010 at 14:37

Back on main subject...
I tried synthesis and it works quite well!

First time I botched it because I accidentally made wrong blend of acids.
(HNO3 3 : 1 HCl)I figured out something is wrong when I got big mushroom cloud of NO2 and
mosquitoes stoped to sting that night... :D
Anyway, in next synth. I got cca. 7g of pure dry crystals from 15g of paracetamole.
Is this good!?

I skipped reflux of p-benzo in alchohol and filtering of boiled solution since it completely dissolved in 200ml of denat. ethanol
with light heating without crude crap leftover and it is obvious killer of the yield.
There were far less crystals than in pics of IPN synth. and they were all at the bottom.
First I let them at the room temp. for 24h and then 12h in the freezer(looks like everything
was already there at the room temp.)
I have few questions:
Is the black liquid they recrystallized them from worth effort!?I poured in few ml of CH2Cl2 and it seems to be miscible?! Is this normal?!
Is 200ml of ethanol too much!? On versuchtchemie they use 200ml isopropyl alcohol so is it more soluble in ethanol than in isopropyl !?

On next paracetamole extraction crystals became pink upon drying !
Is this normal!? It was on the direct sunlight for a day on extremely hot day with high UV index.

Thanks

Alastair - 27-10-2011 at 02:39

Quote: Originally posted by Taoiseach  
Quote: Originally posted by mr.crow  
Quote: Originally posted by Taoiseach  
http://www.versuchschemie.de/topic,13634,-Synthese+von+p-Ben...



I love versuchschemie :)

They mentioned nitrate salts. That would be easier to get and maybe a less vigorous reaction.


No it is very vigorous. I tried it with ammonium nitrate instead of HNO3. Its an amazing reaction - at first the mixture doesn't do anything but all of a sudden it foams up like crazy and gives off thick fumes of nitric oxides. Cooling is crucial to avoid chlorination, which leads to a product contaminated with chloranil.


as far as i understand german ''aber kein Ammoniumnitrat'' is BUT NOT AMMONIUM NITRATE (ie sodium instead of ammonium).
Also i found that para quinone can be reduced with ascorbic acid in water (vitamin C, another otc). this reaction works better in less acidic conditions. (yield hydroquinone)

[Edited on 27-10-2011 by Alastair]

Scr0t - 12-9-2012 at 22:57

I've attempted this method of preparing p-Benzoquinone and compared it to Benzoquinone prepared via HQ/H2O2/I2 by using both as reagents to prepare 5-hydroxy-1,3-benzoxathiol-2-one as described under PIHKAL #167.
Results were markedly different.

Benzoquinone prepared by this method produced a compound that was close in mp (depressed by a couple of Kelvin) however other differences were noted e.g. slightly lower solubility in IPA and it was more difficult to form large crystals from IPA but otherwise closely resembled Benzoquinone.

Apart from a few other differences in observations during the course of the reaction with thiourea the end product did not form large needles of the Benzoxathiolone but formed an off-white powder and did not have a melting point (~170°C) but simply carbonised >200°C.

This leads me to think that the material so obtained is not primarily Benzoquinone but perhaps predominately chlorinated intermediates to Chloranil.
The reaction is not easily controlled by an ice-salt bath and can briefly peak at a Temp >40°C on the 15g scale used in the versuchschemie procedure.

Perhaps Aqua-regia is not a good choice of oxidant here.


Nicodem - 13-9-2012 at 06:57

Quote: Originally posted by Scr0t  
I've attempted this method of preparing p-Benzoquinone ...

Perhaps Aqua-regia is not a good choice of oxidant here.

Just to make things clear, are you referring to the procedure developed by benzylchloride1?
Quote: Originally posted by benzylchloride1  
In an attempt to alter the synthesis of p-chloranil from p-acetamidophenol, I ended up producing p-benzoquinone in a yield of 80%.

...

Thanks for sharing your results.
Interesting coincidence that the melting points are so close. Anybody has the time to review the mp of the most likely candidates? It would be interesting to see what the actual product is. It appears to be a substituted quinone.

Scr0t - 14-9-2012 at 09:34

Quote: Originally posted by Nicodem  

Just to make things clear, are you referring to the procedure developed by benzylchloride1?

Yes.
A similar or the same procedure is also posted on versuchschemie.de.

Nicodem - 15-9-2012 at 04:37

Quote: Originally posted by benzylchloride1  
The melting point was taken with a Haake-Buchler melting point apparatus, the product melted at 117 celsius one degree above the value in the CRC Handbook of Organic Compound Identification, due to a fairly rapid heating rate.

The lit. mp of 2,6-dichloro-1,4-benzoquinone is 122-124 °C or less (depends on the source), while that of 1,4-benzoquinone is 113-115 °C. So, the slightly higher mp might have not been a mistake due to a rapid heating rate. Since benzylchloride1 does not report the melting interval, it is hard to estimate, if his product was a pure substance or perhaps he obtained a slightly impure 2,6-dichloro-1,4-benzoquinone which would explain the 117 °C mp due to its depression.

Given the nature of the oxidant used, it would be unusual to obtain nonchlorinated 1,4-benzoquione as the main product. Finally, taking into account the derivatization results reported by Sc0t, I would say that the identification of the product obtained in this procedure requires a revision.

Certain references support the idea of 2,6-dichloro-1,4-benzoquinone as the product of chlorine reagent based oxidations of substrates that could go through related intermediates:


Quote:
Chem. Abstr. 69: 58917
The soln. of NaClO2 (0.03 mole in 10 ml. H2O) was added dropwise during 1-2 hrs. into a stirred mixt. of 0.01 mole phenol and 25 ml. 2N H2SO4 or 2N HCl. The temp. was kept at 0-5° to give 2,6-dichloro-p-benzoquinone (I), m. 119-20°, as a main product, some chloro-p-benzoquinone, and traces of p-benzoquinone. Similarly, I was obtained from 2,6-dichloro-, 2,4-dichloro-, and 2,4,6-trichlorophenol in the yields 84.9, 32.5, and 59.8% resp.; 2,5-dichlorophenol gave 34.5% 2,5-dichloro-p-benzoquinone, m. 160-1°, and traces of trichloro-p-benzoquinone. The results were independent of the inorg. acid used.


Another example: In the chlorination of phenol with NaClO3/HCl, a 1:1 mixture 2,6-dichloro-1,4-benzoquinone and 2,5-dichloro-1,4-benzoquinone was obtained (Bulletin of the Korean Chemical Society, 32, 472-476; DOI: 10.5012/bkcs.2011.32.2.472). Anisole gave 2,6-dichloro-1,4-benzoquinone as the second major product, right after 2,4,6-trichloroanisole.

JJay - 17-12-2016 at 00:51

I was recently looking through papers for a method to convert acetaminophen to hydroquinone and found several possible routes, all of which go through p-benzoquinone. I like the idea of doing it with hydrogen peroxide in sulfuric acid, but oxidation by aqueous permanganate is well researched and apparently produces a quality product without the need for much purification.



Attachment: 01932691003656938.pdf (369kB)
This file has been downloaded 289 times


JJay - 12-1-2017 at 17:56

I've been meaning to try this out for a few weeks now, and I'm planning on getting started tonight. I made a few changes from the original procedure from the PDF above. In particular, the reaction has been scaled up by a factor of 10. Also, instead of using chloroform, I tentatively plan to substitute ether because it evaporates more readily and I don't have any chloroform prepared. Also, I think ether probably dissolves benzoquinone more readily. In addition, I hope to use less solvent than in the original procedure to avoid wasting solvent and to minimize the impact on the environment.

Acetaminophen is not very soluble in water, so reaction conditions are necessarily dilute. I'm quite sure they don't have to be as dilute as in the original procedure, though, and the stoichiometry looks off, but I'd like to get the synthesis working before doing any further optimization.

---


Proposed Procedure for Preparation of Benzoquinone


Extraction of acetaminophen from OTC pain reliever medication

Crush 10x500 mg acetaminophen pain reliever pills to a fine powder and place in a 250 mL beaker. Add 100 mL of methanol and with strong stirring, slowly heat to just boiling over 30 minutes. Allow to cool to room temperature and gravity filter. Cool the resulting solution to 0 C and then add 100 mL of cold water in small portions. Vacuum filter the product with a glass sinter and extract most of the water on the pump, then dry the product in a dessicator over anhydrous calcium chloride before weighing and placing in a suitable storage container.

Oxidation of acetaminophen

Dissolve 1.20g acetaminophen in 500 mL room temperature distilled water with strong stirring in a 1000 mL beaker. Dissolve 4.00g potassium permanganate in 250 mL distilled water. With strong stirring, add the permanganate solution to the acetaminophen solution and allow to react for several hours or until complete. Gravity filter, and add to a separatory funnel. Extract with 3x10 mL diethyl ether. Combine the ether extracts and wash with 3x50 mL distilled water. Dry the ether solution over a few grams of anhydrous magnesium sulfate. Place the ether solution in a dish and allow it to evaporate at room temperature. Remove and weigh the product, and place in a suitable storage container.


Edit: After reviewing the literature, I tentatively decided to substitute ether instead of DCM for chloroform. I'm still trying to decide exactly what solvent to use.



[Edited on 13-1-2017 by JJay]

JnPS - 12-1-2017 at 21:55

That's an excellent short write-up JJay, I'll definitely be trying that before this semester starts, what was your yield when using ether? I'll try using DCM and we could compare the solvent choices. I'm out of ether from chlorophyll extractions :(

JJay - 13-1-2017 at 01:13

Quote: Originally posted by JnPS  
That's an excellent short write-up JJay, I'll definitely be trying that before this semester starts, what was your yield when using ether? I'll try using DCM and we could compare the solvent choices. I'm out of ether from chlorophyll extractions :(


Thanks. I haven't tried it yet, and I'm still trying to decide for sure what solvent to use. Right now, I'm watching acetaminophen pills dissolve in methanol on a hotplate. They seem to dissolve quite readily (I'm just using the generic Equate brand), so minimal crushing is required.

JJay - 13-1-2017 at 01:58

I have a still slightly-warm solution of acetaminophen sitting in one of my three oldest ground-glass Erlenmeyers. I got impatient and filtered the solution through a cotton ball twice, and the solution is milky. I'm not 100% sure what the cause of the milkiness is... could be talc, titanium dioxide, stearic acid, corn starch, or any number of other substances. I'm going to let it cool overnight before proceeding. Hopefully the milkiness will settle.

Edit: The proposed extraction method didn't work. I think it could work, but the methanol solution should be saturated, and that requires a lot more than 5g of acetaminophen in 100mL of methanol.

I did some searching around and found a couple of procedures for extracting acetaminophen from pills:

BlackDragon2712 obtained very nice-looking crystals using 95% ethanol: lhttp://www.sciencemadness.org/talk/viewthread.php?tid=65167#pid437040
The RSC wrote a guide for educators on acetaminophen that describes an extraction with acetone: http://www.rsc.org/learn-chemistry/content/filerepository/CM...

The crystals in BlackDragon2712's pictures look awfully nice, so I think I'll adapt his procedure. I suspect I can get away with using slightly less ethanol, but first I'm going to try replicating his procedure exactly.

[Edited on 14-1-2017 by JJay]

JnPS - 15-1-2017 at 09:28

Yeah I just tried the methanol prep and I got a small amount of precipitate when adding the cold water to the methanol solution but not enough to bother recovering, I've been saving my 95% EtOH for a rainy day but I don't have much, I'll probably end up following the acetone extraction route

JJay - 15-1-2017 at 09:59

I was thinking about giving the methanol extraction another try but with something more like 20-30g of acetaminophen. I have 4L jugs of ethanol and acetone but only about a liter and a half of methanol... the crystals from absolute ethanol look so pretty, though, so I think I'll try that next.

JnPS - 15-1-2017 at 10:48

Acetone extraction worked great for me, I'm recrystallizing from water just to be safe, but yeah those crystals from EtOH looked amazing, maybe when I'm 21 and can get ethanol more readily I'll try and get those cool looking crystals.

Back to benzoquinone though, should I add the permanganate solution slowly or just mix the two and allow to react?

EDIT: Nevermind, I'm reading the PDF JJay linked to and there doesn't appear to be any reason to slowly add the oxidant

[Edited on 15-1-2017 by JnPS]

JJay - 15-1-2017 at 18:23

I have a crop of acetaminophen crystals growing in the freezer. They don't look as nice as BlackDragon2712's, and they are pretty small (around 0.5 mm long), but they have a similar shape as his, and I think they'll be pure enough for the next step.

Edit: I took the crystals out of the freezer and vacuum filtered them through a glass sinter. Most of the precipitate was a powder, and even the biggest crystals seemed pretty fragile. I washed them a couple of times with water and dried them on a water aspirator for about 10 minutes, and now they are sitting in a makeshift desiccator made out of nested Tupperware containers over calcium chloride in the dark.

For some reason, the powder is light pink rather than white as I would expect. I'm not really sure why... this is obviously some sort of impurity, but the pills started out entirely white, so I suspect it is a decomposition product or a polymer. I started out with 20 grams of acetaminophen, and there appears to be a pretty good amount of product, which I will weigh when it is fully dry.

There has been some research done on acetaminophen decomposition products that form in solution, but they appear to range from yellow to brown rather than pink....

[Edited on 16-1-2017 by JJay]

JnPS - 15-1-2017 at 20:23

I ran the oxidation but I the total volume of filtrate (doing the gravity filtration) is ~750mL. This is too large for my biggest sep. funnel (500mL). Would I be okay boiling off up to half the volume of water so I can do the extraction of the product? Or should I just opt for doing the extraction in two steps?

JJay - 15-1-2017 at 20:50

I'd say do the extraction in two steps. I'm not really sure what boiling off the water would do.

Boffis - 15-1-2017 at 21:45

@JnPS, I would not try boiling off the water as benzoquinone is steam volatile and you will loose most of it to the distillate. I would do as JJay suggested and divide the solution into 2 or 3 portions that you can extract and then extract with dichloromethane, dry the extract and then distil of the chlorinated solvent with reduced pressure distillation to minimise co distillation of the volatile benzoquinone.

DJF90 - 15-1-2017 at 23:37

I would set up for steam distillation and use this property of benzoquinone to advantage. Amarego and Perrin list this as one of the methods for purification, and in your case theres very little else that should pass over.

JJay - 16-1-2017 at 01:44

Interesting... I guess you could run the steam distillation like a simple distillation and then extract the product from the distillate?

DJF90 - 16-1-2017 at 04:29

Benzoquinone is not particularly soluble in water and so should crystallise out. Just collect the distillate, cool in an ice bath to improve the extent of crystallisation and filter to obtain the solids. If further purification is required then sublimation or recrystallisation can be used.

JJay - 16-1-2017 at 07:32

Here's the problem with that approach: There's only a small amount of benzoquinone in the reaction mixture, and I'd rather not sacrifice any to mechanical losses. I'm also not relishing the idea of scraping benzoquinone out of my adapters, condenser, and receiver.

DJF90 - 16-1-2017 at 08:09

I don't think it poses that much of an issue, or it wouldn't be recommended.

See http://www.orgsyn.org/demo.aspx?prep=CV4P0148 for a related compound, also purified by steam distillation (note 12)

JJay - 16-1-2017 at 08:18

They did an ether extraction of the distillate (after filtering) to obtain about 20% more product. They also extended the steam distillation longer than absolutely required to flush the adapters and condenser. Of course, this would result in lower yields without doing an extraction on the distillate.

I think the suggestion to steam distill is a good one, but I'm quite certain that it's a good idea to follow it up with a solvent extraction for the reasons previously mentioned.


[Edited on 16-1-2017 by JJay]

DJF90 - 16-1-2017 at 08:35

You might find that by cooling the distillate in the fridge/ice bath for a few hours might make the solvent extraction unnecessary, but in the first instance a quick extraction with ether or DCM sounds pragmatic.

JnPS - 16-1-2017 at 11:47

I followed JJay's little mini-write up for oxidizing paracetemol via KMnO4, but after extracting both portions with 3 portions of DCM the reaction mixture didn't seem to change color/clear-up and after drying and evaporating the combined DCM layers I was left with a small lonely empty beaker :( I kept my reaction mixture just in case anyone has any idea how to extract any possible product out of it

JJay - 16-1-2017 at 14:58

I am not sure if benzoquinone will dissolve in DCM. It does dissolve in ether and chloroform.

Here I have 10.22 grams of slightly pink acetaminophen extracted from pain reliever alongside some potassium permanganate and 60 mL homemade ether.



IMG_20170116_135158.jpg - 464kB

JJay - 16-1-2017 at 15:12

Quote: Originally posted by JnPS  
I followed JJay's little mini-write up for oxidizing paracetemol via KMnO4, but after extracting both portions with 3 portions of DCM the reaction mixture didn't seem to change color/clear-up and after drying and evaporating the combined DCM layers I was left with a small lonely empty beaker :( I kept my reaction mixture just in case anyone has any idea how to extract any possible product out of it


There is a distinction that I probably should have drawn before... the procedure was not a "write up" - it was a proposal. A writeup should be written in the past tense and have a reported yield. A proposal hasn't actually been tested yet.

I'm reasonably sure that it can be gotten to work. If you have some product in solution, it should be possible to extract it with chloroform, according to the PDF from which I derived the procedure. Other solvents are untested. I am reasonably sure that ether should make a good substitute for chloroform. From a quick search, I didn't see any solid-looking reports where anyone successfully dissolved benzoquinone in DCM, although I don't see any theoretical reason why that wouldn't be possible. I did see one unreferenced comment made on another forum suggesting that it does not dissolve in DCM and a few other comments stating that it does. (Note that I certainly do not possess omniscience with relation to chemistry, so there may very well be a reason that benzoquinone does not dissolve in DCM, but I don't know what it is, if there is one.)


[Edited on 16-1-2017 by JJay]

[Edited on 16-1-2017 by JJay]

Metacelsus - 16-1-2017 at 15:16

I know DDQ dissolves in DCM, and I would expect benzoquinone to have greater solubility. You could probably find an exact value with some searching.

JnPS - 16-1-2017 at 15:28

Thanks for the distinction, I'll try to extract it with chloroform tomorrow, guess I finally found a use for my home-made chloroform. :)

If I manage to get some benzoquinone crystals after that, I'll see if I can get them to dissolve in DCM

EDIT: I just realized @JJay, your acetaminophen is slightly pink, mine was too after extraction so I decided to recrystallize from water. I'm pretty sure we used different brand pills so what a coincidence XD




[Edited on 16-1-2017 by JnPS]

JJay - 16-1-2017 at 19:30

I'm ready to start the reaction.

Reading over that paper again, the calculations they made to estimate the Gibbs free energy don't make sense... they calculated a positive Gibbs free energy at 25 C, which would indicate that the reaction does not happen at that temperature... but they clearly show experimental results indicating that the reaction does proceed spontaneously at 25 C....

The reaction clearly happens more quickly at higher temperatures, so slight heating might not be a bad idea. They have tested the reaction at temperatures as high as 55 C.


JJay - 16-1-2017 at 19:45

When I poured in the permanganate, I could see a definite brown color of manganese dioxide forming before the solution went completely dark.

I still had a tiny amount of undissolved permanganate in my 250 ml beaker, so I rinsed it with about 10 ml of water and added it to the reaction.

IMG_20170116_181652.jpg - 433kB

JnPS - 16-1-2017 at 20:14

I believed the delta G they were talking about was for the formation of the transition state usually denoted by a 'double dagger' symbol but they used a hashtag instead. A positive delta G for the transition state would explain why slight heating is necessary for the reaction. I don't think they were talking about the overall delta G for the reaction.

I had the same issue with the KMnO4, though I used around 50mL of extra distilled water to wash out the beaker. I also kept the reaction mixture around 40C for five hours and the reaction appeared to be finished when I went to begin the work-up. Can you take a picture of your reaction mixture afterwards? I want to see if the color of my solution matches yours.

JJay - 16-1-2017 at 20:36

I was just reading over the paper to figure out how fast the reaction should go, and I think I found a couple of errors. The units on figure 2 don't seem to make any sense... the log of PAM<sub>0</sub>, the initial molarity of the acetaminophen, can't be positive. Surely they meant mmol/dm<sup>-3</sup>. Also, they mistakenly refer to "dichromate" instead of permanganate on the same page as the figure.

Ignoring those obvious errors and doing some crude estimation that assumes the rate equation is first order, it looks like the half life of acetaminophen is about 7 minutes with the initial permanganate concentration at 35 C. That means the reaction would be about 99% complete in an hour.

There are some particles of manganese dioxide floating around, but mostly, the reaction mixture just looks dark. There is a trace of an oil floating on top of it; it looks almost like a gasoline slick. I'll take a picture, but it won't show anything very interesting....


[Edited on 17-1-2017 by JJay]

JJay - 16-1-2017 at 21:12

Whoah.. after turning off my stirrer, something interesting is happening! The manganese dioxide particles are settling to reveal a brownish/yellowish clear solution that likely contains the product!

IMG_20170116_194808.jpg - 443kB IMG_20170116_200931.jpg - 482kB IMG_20170116_204005.jpg - 466kB

So anyway, I don't know for sure yet, but it looks pretty likely that I have some benzoquinone.

[Edited on 17-1-2017 by JJay]

JJay - 16-1-2017 at 22:22

Here's the problem I'm running into with ether: it's too soluble in water! I added 30 mL of ether to the approximately 700 mL of solution, saw two layers form, shook it, and the top layer disappeared! If I add the entire 60 mL, I get a very small layer.

I only had 60 mL of ether, and I'm pretty reluctant to handle a larger quantity in this location, so it looks like I might have to make some chloroform....

Boffis - 16-1-2017 at 23:02

@JJay, yes ether is slightly soluble in water, about 3g per 100g of water, so thats why your ether layer dissolved. However, dispare not. You can reduce this figure and the solubility of benzoquinone too by adding salt to the aqueous liquid, up to about 20g per 100ml of aqueous phase but 15g is probably enough in your case. The addition of salt may be sufficient to salt out the benzoquinone anyway.

I tend to try methylene dichloride (dichloromethane) first because it is cheaper and more readily available but is less polar and so not a perfect substitute.

JJay - 16-1-2017 at 23:16

@Boffis: I was seriously considering giving that a try but figured that since the reaction was so simple and the reactants are cheap there was no point really, so unfortunately, it's in an organic waste container outside at this point and I've washed and put away my glassware... I definitely do appreciate that suggestion, though, and I'll have to try again in the near future, perhaps tomorrow.

[Edited on 17-1-2017 by JJay]

JnPS - 17-1-2017 at 06:30

Your solution looks more red than mine does, but I don't think color differences are a huge concern. I guess I'll try salting it out first and if I don't get any benzoquinone from that I'll just scrap my reaction mixture and try the reaction again using chloroform for the extraction.

PHILOU Zrealone - 17-1-2017 at 08:22

Interesting to see that the protons for the oxydation comes from:
-the phenolic moeity --> phenate
-the hydrolysed acetyl group --> acetic acid

So the pink color may come from excès KMnO4, manganese(II) phenate or acetate :).

JJay - 17-1-2017 at 13:32

The solution actually wasn't pink to my eyes... more of a yellow to brown color. There was a trace of violet on the sides of the beaker from splashing, but that was just KMnO4 and not very much of it... that stuff has an extremely intense color.

Benzoquinone is yellow and tar is brown... but perhaps pink mixed with yellow looks brown... IDK.

JnPS - 17-1-2017 at 14:12

I added 120g of salt to my 800mL of solution and It still yielded no yellow precipitate, all I filtered off was a bit of MnO2 dust that remained. I won't be able to be in my lab again until Saturday morning, but I'll re-run the oxidation and try extracting with chloroform. I'll keep an eye on this thread to see if JJay manages to beat me to the benzo


JJay - 17-1-2017 at 17:35

I am swamped with work tonight, but I'll definitely start on it before this weekend.

Boffis - 18-1-2017 at 11:14

@JJay and JnPS, have you considered the reaction that is actually occurring and its stoichiometry. The paper you posted on the 17th Dec is short on actual experimental detail as it is not really about the preparation of benzoquinone but rather about the distruction of paracetamol and other pharmaceuticals in waste water, hence while KMnO4 may be used in excess it is also carried out in very dilute soutions. I have tried to work out a plausible reaction scheme and come up with the following equation:

6C<sub>8</sub>H<sub>9</sub>NO<sub>2</sub> + 10KMnO<sub>4</sub> &rarr; 6C<sub>6</sub>H<sub>4</sub>O<sub>2</sub> + 6KC<sub>2</sub>H<sub>3</sub>O<sub>2</sub> + 4KOH + 3N<sub>2</sub> + 10MnO<sub>2</sub> + 4H<sub>2</sub>O

The products other than benzoquinone are potassium acetate, potassium hydroxide, nitrogen and Mn dioxide.

From this equation is follows that for 1.2g of paracetamol roughly 2g of KMnO4 are required, about half the amount you used. While benzoquinone is fairly resistant to further oxidation it is not indistructable. Your large excess of oxidant may break the benzoquinone down to oxalic acid and similar compounds. In support of this idea is the red-purple solution you obtained; the Mn3+ oxalato complex is of about this colour.

So the problems you are having isolating the benzoquinone may be due the the facr that there isn't much there! I suggect you try the reaction again with less permanganate.

JJay - 18-1-2017 at 11:50

"After complete degradation of acetaminophen, which was
confirmed from no change in absorbance after 90 minutes,
the whole reaction mixture (acetaminophen=2x10<sup>-2</sup>
mol dm<sup>-3</sup> i.e., 0.120gm in 50 ml distilled water and
KMnO<sub>4</sub>=10x10<sup>-2</sup>mol dm<sup>-3</sup> i.e., 0.400gm in 25 ml distilled
water) was extracted with 50 ml chloroform. The
chloroform layer was washed with 350 ml distilled water.
Chloroform was evaporated and the product obtained was
crystallized. The product obtained was compared with benzoquinone
by spot method.[27] Melting point of these crystals
was similar to that of benzoquinone (m.p.=114–116C).
Sultan also suggested similar products by using different
oxidant.[28] Free radical formation was confirmed following
the literature method.[29] Product formation was further
supported by detection of ammonium ions in solution that
was verified by spot test.[28]"

I think the suggestion to try again with less permanganate is a good one. The excess permanganate is being consumed somehow or the solution would be dark purple when the reaction completes, and if it's being consumed destroying the benzoquinone, that's almost certainly not desirable.

AvBaeyer - 19-1-2017 at 15:32

I have read the paper posted by JJay a while back. It is truly not useful as the basis of a synthetic method for obtaining benzoquinone from paracetamol. The mechanism that is proposed in the paper at step 9 (hydrolysis of N-acetylamidobenzoquinone imine [NABQI] to benzoquinone) makes no sense whatsoever. NABQI is a notoriously unstable compound unless special precautions are taken during it synthesis. It is an extremely electrophilic compound among other things. The information given in the paper (quoted in the above comment by JJay) is completely indeterminant. The product was compared to benzoquinone by a spot test but no result is stated. The product had a melting point "similar to benzoquinone" - a garbage statement. Despite all the effort being put into this KMnO4 oxidation, I suspect that you are not going to find success.

See the following for some insight:
Tet. Lett. 1980, v21, 4947
J. Med. Chem. 1982, v25, 885

There is a lot more if you do a Google scholar search.

AvB

JJay - 19-1-2017 at 16:20

Quote: Originally posted by AvBaeyer  
I have read the paper posted by JJay a while back. It is truly not useful as the basis of a synthetic method for obtaining benzoquinone from paracetamol. The mechanism that is proposed in the paper at step 9 (hydrolysis of N-acetylamidobenzoquinone imine [NABQI] to benzoquinone) makes no sense whatsoever. NABQI is a notoriously unstable compound unless special precautions are taken during it synthesis. It is an extremely electrophilic compound among other things. The information given in the paper (quoted in the above comment by JJay) is completely indeterminant. The product was compared to benzoquinone by a spot test but no result is stated. The product had a melting point "similar to benzoquinone" - a garbage statement. Despite all the effort being put into this KMnO4 oxidation, I suspect that you are not going to find success.

See the following for some insight:
Tet. Lett. 1980, v21, 4947
J. Med. Chem. 1982, v25, 885

There is a lot more if you do a Google scholar search.

AvB


According to this paper, p-benzoquinone is obtained from hydrolysis of NABQI.

I definitely think it's worth another try.


Attachment: ja00194a046.pdf (1.2MB)
This file has been downloaded 154 times

Edit: I'm still reading over this paper to try to avoid making any erroneous conclusions and to try to determine experimental conditions.

[Edited on 20-1-2017 by JJay]

Magpie - 19-1-2017 at 16:52

speculation:

Could the acetyl group be removed (as in a protective group removal) leaving p-aminophenol? From there one could diazotize then acidify to form the 2nd OH group, giving hydroquinone. Benzoquinone should be easy from there, if desired.

http://www.synarchive.com/protecting-group/Amine_Acetamide

PHILOU Zrealone - 20-1-2017 at 05:14

Quote: Originally posted by Magpie  
speculation:

Could the acetyl group be removed (as in a protective group removal) leaving p-aminophenol? From there one could diazotize then acidify to form the 2nd OH group, giving hydroquinone. Benzoquinone should be easy from there, if desired.

http://www.synarchive.com/protecting-group/Amine_Acetamide

p-amino-phenol will yield a relatively stable diazo-phenoxide...concentrated acid will simply make the diazonium back. See DDNP tread into energetic material section

Hydrolysis of paracetamol is exposed into that vast tread as a starting material for iso-para-diazo-dinitrophenol.

I think that maybe to submit p-amino-phenol to water hydrolysis into the warm (acidic or basic?) will take the NH3 off.
Because phenols as their name indicates are enols...and so anilins are enamines...as discrete transcient structure
-CH=C(-OH)-CH= <----> -CH2-C(=O)-CH=
-CH=C(-NH2)-CH= <----> -CH2-C(=NH)-CH=
This is proven by much specific organic reactions like picric acid (trinitrophenol) conversion to picramide (trinitroanilin) with NH3; or like the formation of cyclohexan-trion-trioxime from phloroglucidol (1,3,5-trihydroxybenzen) and hydroxylamine.

JJay - 20-1-2017 at 13:14

It might be met with utter failure, but I am going to make an attempt at oxidizing acetaminophen again tonight in an acetate buffer with a stoichiometric amount of permanganate.

JJay - 20-1-2017 at 14:01

Quote: Originally posted by Magpie  
speculation:

Could the acetyl group be removed (as in a protective group removal) leaving p-aminophenol? From there one could diazotize then acidify to form the 2nd OH group, giving hydroquinone. Benzoquinone should be easy from there, if desired.

http://www.synarchive.com/protecting-group/Amine_Acetamide


If acetaminophen can be easily de-acetylated by reflux in potassium hydroxide, I think sodium dichromate could be used to oxidize it to benzoquinone. DJF90 pointed out earlier this oxidation of a chlorinated aminophenol to benzoquinone with sodium dichromate, and the researcher mentioned in the notes that he's prepared benzoquinone by this same reaction at 5-10 C: http://www.orgsyn.org/demo.aspx?prep=CV4P0148

Other oxidants might work too.



Magpie - 20-1-2017 at 16:12

Quote: Originally posted by PHILOU Zrealone  

p-amino-phenol will yield a relatively stable diazo-phenoxide...concentrated acid will simply make the diazonium back.


Thanks PHILOU for your comments. I don't have the depth of knowledge about diazotization to add much here. I understand that diazonium ions can couple with themselves if sufficiently electron rich as I imagine a phenol might be.

This link shows a Chinese patent that purports to use this technology to make resorcinol. Using the patent translator I converted this to English from Chinese. Then I went a step further and converted the "Example 1" into English usable to me. This is shown in the attached Word file.

Do you think this patent is untrustworthy?


Attachment: Preparation of Resorcinol CN105601476.doc (30kB)
This file has been downloaded 239 times

PHILOU Zrealone - 20-1-2017 at 17:55

Quote: Originally posted by Magpie  
Quote: Originally posted by PHILOU Zrealone  

p-amino-phenol will yield a relatively stable diazo-phenoxide...concentrated acid will simply make the diazonium back.


Thanks PHILOU for your comments. I don't have the depth of knowledge about diazotization to add much here. I understand that diazonium ions can couple with themselves if sufficiently electron rich as I imagine a phenol might be.

This link shows a Chinese patent that purports to use this technology to make resorcinol. Using the patent translator I converted this to English from Chinese. Then I went a step further and converted the "Example 1" into English usable to me. This is shown in the attached Word file.

Do you think this patent is untrustworthy?



It is trustworthy...

Meta-amino-phenol doesn't form diazo-oxides; only ortho-amino-phenol and para-amino-phenol do.
If you read the DDNP tread, you will see that the formation of diazo-oxide seems to have a link with (require) the possibility of a quinonic structure formation...while p-quinon or o-quinon are possible; m-quinon is not.

For the same kind of reason, you get benzotriazole from o-diamino-benzen diazotation and another weird imino-diazo-compound from p-diamino-benzen and no or with difficulty bis-diazoniums...while m-diamino-benzen provides exclusively the bis-diazonium (and coupling products if accessible positions onto another aminobenzenic molecule; or triazenes if position unavailable).

Diazoniums are really strange and fascinating weird beasts.

JJay - 20-1-2017 at 22:55

I think this is the balanced equation for oxidation of acetaminophen to NAPQI:

2 C8H9NO2 + KMnO4 -> 2 C8H7NO2 + KOH + MnO2 + H2O

Here's what I'm about to try:

--

Place 3.64 grams of sodium bicarbonate in a 1000 mL beaker. Add 50.00 mL 5% distilled vinegar. Dilute the resulting buffer to 500 mL with distilled water and dissolve 1.20 grams acetaminophen in it then cool to 0C on an ice bath.

Dissolve 0.63 grams potassium permanganate in 50 mL distilled water and chill to 0C.

Mix the two solutions thoroughly and allow to slowly warm to room temperature, then filter and extract the product with a suitable solvent.

--


JJay - 21-1-2017 at 08:19

I just noticed something that I didn't notice in my last attempt: There is a pale precipitate on top of the dark brown precipitate. I can't see its color clearly due to the dark solution.

I'm not too sure about what that is... I'd think benzoquinone would be somewhat soluble... with 550 mL of solution and the solubility of benzoquinone being 11.1 mg/mL at 18 °C... around 6 grams would dissolve... but there are ions in solution... hmm....

I think it is premature to declare victory, but I'm very curious about what the precipitate is.

JJay - 22-1-2017 at 16:56

I haven't forgotten about this, but I've been busy with other things and haven't done the workup yet. I did take out my beaker and take a look at it earlier, and the solution is visibly much darker than it was previously... it's now almost opaque, and the precipitates are not visible. Not sure why....

I decanted the contents into another beaker and observed as I was pouring the mixture that there are most definitely two different precipitates: A dark one that I assume is manganese dioxide and a fluffy lighter one that *hopefully* is benzoquinone.

I'm going to try steam distilling first and then do a solvent extraction if I see any product.

JnPS - 22-1-2017 at 19:11

So the purpose of performing the reaction in an acetate buffer was simply to reduce the solubility of benzoquinone in the reaction mixture? If you get any product let me know so I can try and repeat the procedure. I'll start looking to buy the vinegar necessary to make the buffer in the mean time between classes.

JJay - 22-1-2017 at 19:28

The effect of an acetate buffer was to increase the yield from hydrolosys of NAPQI in the paper cited here: http://www.sciencemadness.org/talk/viewthread.php?tid=8250&a...

I tried to make the pH at the midpoint of the oxidation equal to 5.6.




[Edited on 23-1-2017 by JJay]

Magpie - 23-1-2017 at 13:31

I was doing some reading in Groggins, "Unit Processes in Organic Synthesis," 3rd ed (1947), a chemical engineering text. There I found a synthesis for "quinone." (Quinone is an archaic name for p-benzoquinone.) What surprised me is that the precursor was aniline. Here's the synthesis:

"A mixture of 25 parts aniline, 200 parts of water-white sulfuric acid, and 600 parts of water, contained in a wooden or corrosion-resistant vat, is cooled by ice or refrigeration. A solution of 25 parts of sodium dichromate in 100 parts of water is then slowly added with agitation, and stirring continued for 12 hrs. A solution of 50 parts of sodium dichromate in 200 parts of water is then added, and stirring continued until the reaction is complete. During the whole operation, the temperature is maintained below 5°C through the addition of ice or by refrigeration. Quinone is recovered by skimming from the surface of the solution and purified by steam distillation.

Oxidation of aniline with MnO2-H2SO4 mixtures is claimed to give 73 per cent yield of quinone (Gibbs, US patent 2,343,768)."

JJay - 23-1-2017 at 15:13

Aniline has largely fallen out of favor as a precursor to benzoquinone in the U.S. and Europe due to environmental regulations, but that process is still widely used in China.

I am curious as to whether the dark color in my beaker is due the formation of a quinhydrone complex between hydroquinone and benzoquinone. I'm not completely sure what would cause hydroquinone to form in solution, but it seems plausible that some of the NABQI attacked the some of the product and reduced it to hydroquinone.

I am not sure if I will have time to run the steam distillation today, but I will definitely get to it in the next couple of days.

[Edited on 24-1-2017 by JJay]

Amos - 24-1-2017 at 07:12

For those looking into the NAPQI route, I know there are a lot of p-substituted aniline derivatives in hair dyes that are converted to the corresponding imine using hydrogen peroxide (the "developer"), so this may be a cleaner method of oxidizing the paracetamol.

JJay - 24-1-2017 at 22:26

After steam distilling off 50 mL of water, I can see that there is definitely a solid floating in it, but it doesn't look very yellow, and there's very little of it. If I look at the very largest particle, it looks like it might be yellow, but it's hard to be 100% sure under these yellow lights. The particle is a little bit darker than a piece of typing paper. There might be some benzoquinone here, but it's only maybe a few hundredths of a gram. I've read that benzoquinone smells like chlorine, and this substance has a sharp smell that reminds me of chlorine if I take a strong whiff (which I probably shouldn't do), but it reminds me of nitric oxide more than chlorine. The material left in the boiling flask has the same odor, but it is very weak. Oddly, I don't smell any acetic acid.

There might be a measurable amount of recoverable product here, but I don't have the equipment I would need to handle such tiny quantities, so I guess I will discard it.

...I just read that benzoquinone smells like a cross between chlorine bleach and burning plastic. That is a more apt description of the smell, but I didn't see the neon yellow color that is characteristic of benzoquinone, so I am skeptical that the substance that steam distilled over was actually benzoquinone.



[Edited on 25-1-2017 by JJay]

Magpie - 26-1-2017 at 15:08

Quote: Originally posted by JJay  

If acetaminophen can be easily de-acetylated by reflux in potassium hydroxide, I think sodium dichromate could be used to oxidize it to benzoquinone.


This is supported by Cason & Rapoport in their "Laboratory Text in Organic Chemistry," (1950), p. 332.
I quote: "... the best yields of p-benzoquinones are obtained by oxidation of derivatives having amino or hydroxy in para positions." "Oxidation of crude aminophenol often gives yields of quinone amounting to 80-95 percent..."

[Edited on 26-1-2017 by Magpie]

JJay - 26-1-2017 at 17:45

Quote: Originally posted by Magpie  
Quote: Originally posted by JJay  

If acetaminophen can be easily de-acetylated by reflux in potassium hydroxide, I think sodium dichromate could be used to oxidize it to benzoquinone.


This is supported by Cason & Rapoport in their "Laboratory Text in Organic Chemistry," (1950), p. 332.
I quote: "... the best yields of p-benzoquinones are obtained by oxidation of derivatives having amino or hydroxy in para positions." "Oxidation of crude aminophenol often gives yields of quinone amounting to 80-95 percent..."

[Edited on 26-1-2017 by Magpie]


Chem Player posted a video on de-acetylation of acetaminophen with sodium hydroxide: https://www.youtube.com/watch?v=lIw82Vjp0rk It looks as though p-aminophenol is easy to prepare but hard to purify completely.

I only have a small amount of potassium hydroxide and have sodium hydroxide in great abundance. I'm going to be looking at a location where I might be able to set up a lab next week, so I hope to give it a try.

JJay - 3-2-2017 at 23:12

I'm going to be attempting de-acetylation of acetaminophen this weekend. I plan to follow Chem Player's procedure with a few variations, something like this:

1. Dissolve 4g NaOH in 25 mL of water and add to a 50 mL flask.

Chem Player used "10 mL of water and an ice cube" to dissolve 4g NaOH and ended up with about 25 mL of solution. So I think this is about the right amount of water. Chem Player also used a 100 mL flask, but I think 50 mL is sufficient.

2. Add 5g acetaminophen with stirring.

3. Fit the flask with an air condenser and heat on a boiling water bath with stirring until the internal temperature reaches 90 C for an hour..

Chem Player didn't use a condenser and simply heated the flask on a hot plate on low heat. I don't know exactly what temperature is optimal. I suspect it would be fine to use a small beaker or Erlenmeyer flask directly on a hotplate on low heat with no condenser.

4. Filter the hot mixture and wash the filter cake with a small amount of hot water.

5. Neutralize the mixture to as close to pH 7 as possible with hydrochloric acid.

It's pretty easy to calculate how much hydrochloric acid would be required with a 100% yield. So I'll add that much and then add a little more, checking the pH as I go if necessary.

6. Chill the mixture to close to 0 C and filter.

At this point, after drying, we will [hopefully] have a crude product. Chem Player attempted to purify theirs by recrystallization and found it difficult due to decomposition. I don't know for sure, but it may be feasible to simply use the crude product directly to make benzoquinone. If additional purification is required, perhaps one could simply dissolve the crude aminophenol in a suitable nonpolar solvent and precipitate it as the hydrochloride salt with dry HCl gas. One possible problem with doing this is that to obtain p-aminophenol freebase, one must neutralize the HCl and then extract the p-aminophenol somehow, and that might cause additional decomposition. Also, this won't necessarily remove nitrogen-containing impurities.

I think I'm going to try using the crude product, perhaps with one recrystallization, in an oxidation with sodium dichromate to produce benzoquinone and see how it works out.

Boffis - 4-2-2017 at 22:10

@ JJay, I wouldn't bother trying to purify the p-aminophenol, its very sensitive to oxidation. Also avoid chloride ions and hydrochloric acid if you are going to carry out the oxidation to benzoquinone under acid conditions as you tend to generate chlorohydroquinol by the addition of hydrogen chloride to benzoquinone in aqueous solutions. This compound is then oxidized to chlorobenzoquinone and so on. I use this process deliberately to generate chloranil. At low temperatures the process tends to stop at mono and dichloro compounds but that make purifying the product difficult and increases the consumption of oxidant. When I carry out the latter reaction now I boil the paracetamol with 30-32% hydrochloric acid for an hour under reflux to hydrolyse the acetamido group, cool and then add the saturated solution of oxidizing agent to the reaction mixture so the temperature rises steadily to about 90 C and then maintain this temperature until chlorine evolution becomes significant, then add some more 36% hydrochloric acid and reflux for a further 45 to 60 minutes.

In your case the target is benzoquinone so I would use 50-70% sulphuric acid, reflux for an hour, cool and then start adding your sodium dichromate solution and keep the mixture cool.

JJay - 4-2-2017 at 22:31

Quote: Originally posted by Boffis  
@ JJay, I wouldn't bother trying to purify the p-aminophenol, its very sensitive to oxidation. Also avoid chloride ions and hydrochloric acid if you are going to carry out the oxidation to benzoquinone under acid conditions as you tend to generate chlorohydroquinol by the addition of hydrogen chloride to benzoquinone in aqueous solutions. This compound is then oxidized to chlorobenzoquinone and so on. I use this process deliberately to generate chloranil. At low temperatures the process tends to stop at mono and dichloro compounds but that make purifying the product difficult and increases the consumption of oxidant. When I carry out the latter reaction now I boil the paracetamol with 30-32% hydrochloric acid for an hour under reflux to hydrolyse the acetamido group, cool and then add the saturated solution of oxidizing agent to the reaction mixture so the temperature rises steadily to about 90 C and then maintain this temperature until chlorine evolution becomes significant, then add some more 36% hydrochloric acid and reflux for a further 45 to 60 minutes.

In your case the target is benzoquinone so I would use 50-70% sulphuric acid, reflux for an hour, cool and then start adding your sodium dichromate solution and keep the mixture cool.


Interesting. So neutralizing with hydrochloric acid might not be such a great idea.... I can certainly use sulfuric instead.

Doing the hydrolysis with sulfuric acid could potentially make things easier....

Edit: After thinking this over a bit more, it appears that HCl would likely not present a huge problem if removed before the oxidizer is added. But yes, chloride ions in the oxidation reaction would lead to problems.


[Edited on 5-2-2017 by JJay]

Boffis - 5-2-2017 at 04:31

@JJay, yes if you free base the aminophenol and then isolate it you'd be fine but its just one more operation in which to loose you primary reactant.
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