Aspirin to Acetaminophen - Part 6 of 6: Acetaminophen from p-aminophenol
HTML-код
- Опубликовано: 30 сен 2024
- This is the final part of the series, where the p-aminophenol is converted to the acetaminophen.
Using acetic anhydride, the p-aminophenol is going to be acetylated. The reaction is carried out in water at room temperature.
Acetic anhydride does react with water, but it happens slowly. By including an excess of acetic anhydride, we can assure that the acetylation goes to completion.
Procedure (on page 14): goo.gl/2PDLVn
-------------------------------------------------------------------------------
Merch - nilered.tv/store
-------------------------------------------------------------------------------
■ NileRed is now available on Nebula! go.nebula.tv/n...
(when signing up with this link, a portion of your membership directly supports the channel)
Join the community:
Patreon - / nilered
Discord - / discord
NileRed Newsletter - nile.red/home#...
You can also find me here:
Facebook - / nilered2
Instagram - / nile.red
Twitter - / nilered2
Nile talks about lab safety: • Chemistry is dangerous.
Audio work: Kyle Gamble (kylegambleaudio@gmail.com)
If anyone wants NileRed beakers, I am selling some at my new online store: www.nilered.ca
As things expand, I'll start selling more glassware and accessories.
NileRed i almost bought the set but shipping doubled the price...great work though!
Hey Nile, i was wondering if u could make a video about singlet oxygen. You could make a
qualitative video...would be the first on RUclips :D
Sometimes I hate to live in Europe :D
Why does the Acetic anhydride not attack the OH as well as it would making Aspirin 😷
I got a bunch of now red equipment that I made for half the price hit me up and got sum
Caffeine total synthesis.
Please.
Duly noted. Ill try to make that the next one
jhunkubabu Check lambdasyn on Google
My teacher uses to say, WHY IN THE FUCK WOULD YOU SYNTHETIZE SOMETHING IF A PLANT CAN DO IT!? those same words... It would be interesting, it is fun to make such a complex compound, the rings are beautiful
you know Taxanes? a highly potent cancer-drug, found only in the bark of some rare pacific yew .. it almost got extinct until someone found at-least a partial-synthesis :/
extracting is always better if its cheaper, but thats not always the case
What say, NileRed?
Start with only elements and make a chocolate cake
Okay, doing that now. brb
@@NileRed well...¿
@NileRed did it happen?
@@pcxo2213He died
omg is that cute stirr bar again *.*
ikrrr goals :D
ficolas2 I think it's called a Fish
Yes. Do another one. This was a great series to follow, man! Well done!
will do!
7:50 "I never wanted some high amount of yield".
Estimated a yield of 33% in the beginning :D
He meant high yield wasn't the goal of the exercise
make methenphetamine
Caffeine total synthesis.
Also great work. Really informative.
Thanks!
*I'd love to see the total synthesis of caffeine please.*
This was insanely cool. You've really shown how complicated organic chemistry can be.
As for what I'd like to see next, personally, is Chromium Trioxide and then PCC. I love me some oxidizers (the first reaction I did on my own was KMnO4 + H2SO4 + MeOH, EtOH, and any other alcohols I could get my hands on, because life, for me, just isn't exciting if I'm not singing my eyebrows. :)
I'd love more longer projects like this!
Hey I do LC-MS as a career. I love your videos and would like to help out in any way possible. Thanks for the continuing education and the wonderful videos. :)
Cool! I might take you up on that offer one day
this was a great series to follow
whoeveriam0iam14222 same here
Thanks!
Hey, @nilered have you thought of trying to convert acetaminophene to aspirin? ;)
haha, i think ill pass for now. I have thought of making aspirin from phenol, but I cant do the carboxylation at home (at least without some engineering efforts). The pressure and temperature needed is just too much.
NileRed Just can't handle the pressure:)
Vielsmeier reaction (POCL3/DMF) give aldehyde, oxydation and you have carboxylic acid
+NileRed You could formylate (Reimer-Tiemann is probably easiest) to salicylaldehyde (which has an interesting aroma, if that sweetens the pot for you ^^) and then do a Lindgren oxidation to get salicylic acid? Acetylisation with acetic anhydride should be ok.
Cool stuff!
As a non-chemist, I'm eagerly anticipating your NMR video - spectroscopy is downright "magical" in what it can reveal, and I'd love to know more about how it works. If you can expand on different types, limitations of each, requirements for the examined material etc. all the better!
Well, solid state NMR (testing solids) has a technique called magic angle spinning....
Making acetone from isopropyl alcohol with permanganate as an oxidizer.
Your initial prediction of 34% made me roll my eyes instantly, but even I did not expect you to fall below 1% :D
Math says you need an average yield of 47% to achieve 1% btw
caffeine total synthesis sounds exciting. Btw: I wanted to ask what kind of degree you have, because you sometimes say some chemicals were tough to get. For example the acetic anhydride is 36,50€ per liter where I live, all that is necessary is a paper evidence that you have the necessary knowledge in handling the respective chemicals. I don't know though, if it is just because of the drug control thing you mentioned. As always thank you for your content =)
Felixkeeg, Nile has said before he has a B.Sc. in Biochemistry.
+Humberto Castro
Ahh, thank you!
Felixkeeg h
Atropine from Datura...
Turn aluminum into gold!!! That's chemistry right?
Do R/C! more like nuclear physics
Brok3nC4rrot or alchemy:)
Do R/C! It would be nuclear physics
al·che·my
ˈalkəmē/
noun
the medieval forerunner of chemistry, based on the supposed transformation of matter. It was concerned particularly with attempts to convert base metals into gold or to find a universal elixir.
Do R/C! There you have it... MEDIEVAL. Turning elements into other elements is called nuclear physics. Chemistry is putting elements together
The low yeld, beside the recrystalizations, is probably due to the fact that you used water as solvent: acetic anhydride is notoriusly sensibile to water, being hydrolized to acetic acid. Usually all the acetilation process via acetic anhydride are conducted in a water free environment.
Nitrous oxide, uracil and caffeine synthesis sound interesting :)
You should try making your own acetic anhydride.
I'm a tiny bit disappointed you didn't acetylate using aspirin :)
Loving the final yield, thanks for entertaining someone who understands!
Hey! Can you extract Pelargonic Acid from potatoes or orange flesh next?
By the way, keep up the good work on your channel, I've been bingewatching all your videos.
Would love to see the caffeine total synthesis! Great series!
so are you confident enough in the chemistry to actually take that Tylenol?
Kevin Klika he knows how good he washed the beacons so he knows it could be contaminated with sth he has no reason to take it because he already prooved the purity
Kevin Klika you should never consume anything you made in the lab. There could be all kinds of contamination depending from what you used the glassware for in the past.
Colin Ries I'm interested, what potencial contamination could there be?
talha yaprak all kinds. He did distill mercury. There's a big chance that some equipment he used in this synthesis was also used in the mercury distillation. Furthermore, most of the chemicals he used probably weren't food-grade, so every single chemical introduced its own contaminants. Sodium hydroxide is produced in process involving mercury (which is BTW one of the primary sources of mercury in the atmosphere). So yeah, it's really not a good idea to try it.
arthroxon nö He also explained that the purity was only determined by H-NMR and no trace metal analysis (such as for mercury, palladium, etc.) was done. To sufficiently purify it would require a couple of passes through some ion exchange columns, followed by at least 2 passes through a proper UHPLC system with food grade C-18 silica and solvents, oh and all of this would have to be done with completely new glassware as well (you really can't get the mercury out of the glass by washing with acids or bases or even through chelation, because the mercury diffuses into the glass lattice and slowly seeps back out over time).
So basically, yes he could very easily purify the product to meet the required purity standards, but it would literally cost HUNDREDS of thousands (if not millions) of Dollars (just look up the pricing of preperative UHPLC systems + C-18 silica + USP & HPLC grade solvents...).
Hello Nilered, will you show us how to purify gold that is heavily contaminated with other metals?
drvelocci please stop spamming - nobody cares about your channel, and spamming pretty much guarantees that they won't check it out.
You've already posted this crap several times in this comment section. I'd encourage everyone to report you to RUclips, as I did.
TCPO and nylon!You have promised like years ago about this,as I remembered.
TCPO
Caffein total Synthesis
nice video (as always). is it possible for you to do a synthesis with column chromatography as prufication method? it's the most common method in organic synthesis and i'm missing it a little bit (although i'm doing them every day....sounds stupid i know)
I know it's not on your list, but is it possible to make sucralose? Or to extract a pure form from the packets? Nothing warms the heart like some 1,6-dichloro-1, 6-dideoxy-β-D-fructofuranosyl-4-chloro-4-deoxy-α-D-galactopyranoside.
I wonder, could you do the opposite and make acetylsalicylic acid from acetaminophen?
I guess removing that NH and placing a carboxylate group on that benzene ring might be quite a challenge.
piranha031091 starting from Phenol its possible to use the Reimer-Tieman reaction to get Salicylaldehyde which can be oxydised to salicylic acid
But I dont know how to get to phenol from aminophenol
piranha031091 Tali-bahn NH2 on benzene ring can be removed by nitrous acid (diazotisation) followed by borohydride reduction.
Getting the acetyl group off the amine without destroying the aminophenol is a bit of a trick too.
I guess that's it! Acid hydrolysis to aminophenol, diazotization & reduction to phenol, Riemer-Tieman to salicylaldehide, oxidation with KMnO4 to salicylic acid, and esterification to aspirin.
it's really funny that someone looked at his aspirin tablets and think "as paracetamol you 'll be so mich better" and turn the stuff into paracetamol. i find that funny/interesting and overhaul it was great !
(tips :to improve your yeld use virgin sacrifice as catalist at any given step 66% more % yeld guaranted !)
After all of that you barely have enough to cure one of the headaches this project must have caused :P. Loved the series. Thanks for the videos.
How to dispose of the final product... That's the real headache.
fburton8 😂
Sulphur trioxide or nitrous oxide please and yes the series is complete, congrats 😤 for it.... but sorry for your bad yield ....
Were not a synthesis only associated with acetic anhydride linked with a higher yield? Acetic anhydride and water react to acetic acid, and I would say that the amount of water you have used has converted all the acetic anhydride into acetic acid ...
Total synthesis of a simple natural product
Nitrous oxide pls.
And racetams seems like good idea too.
Oh geez Rick...I don't think he can do that.
If the efficiency of all steps was 100%, total yield would be 89.9 g
I'm a student in chemisty (bac) and I truly love your video and some time they teach me new reactions. I want to says thank you and i hope to see more video of you. Puissiez-vous continuer jusqu’à ce que l'aube ne puisse plus se levé.
why do you not reflux the p-aminophenol, acetic anhydride and water at the beginning?
My vote is for caffeine total synthesis, although I'll watch any of those! Thanks!
Enuf drugs. Let's see some useful polymer synthesis and manipulation.
something interesting to try, making sodium metal through electrolysis, dissolve salt in water, use separate cell electrolysis, collect the sodium hydroxide in anhydrous form, then melt and electrolyse that to create sodium metal in an inert atmosphere. it's not difficult chemistry but it would make a nice series. or perhaps you could collect the chlorine that comes of from the separate cell electrolysis, run it through the aqueous sodium hydroxide to make bleach. all from salt water
I might eventually do that
synth/extraction of nicotine? plus titrating in soln to determine concentration? extraction would be pretty straight forward, synth would be ??? and titration re: concentration i haven't seen you do yet.
That would be really cool but really dangerous as well as the lethal dosage of pure nicotine is like 30 - 60 mg. I'd imagine the total overall synthesis wouldn't be too difficult though if you had access to the required chemicals. After all its only a matter of starting off with the required bromopyridine and then forming a N-methyl-pyrrolidine ring in a few separate steps.
Do Full Version
Looks like you finally got rid of that pink 😂😂😂
I would love to see some really complex synthesis, like vitamin B-12.
you should make a hormone like cortisone or progestins
ok now do sudafed to meth... you know, for research
Yay!
*Nitrous oxide
I think making basic silicone fluids would make a good series with a lot of jumping off points for making other silicon-based materials
hmm interesting
caffeine total synthesis or nylon 6 and nylon 6,6
my vote is for Caffeine Total Synthesis.
Had to smile a bit at the choice of your ppm range ;)
..skipped the 1.5 ppm peak? :P
But very nice videos - love watching these! Keep up the good work!
As a proposal why not try the Fremy's salt synthesis and oxidation of phenol to p-benzoquinone. Nice colorful chemistry although the prepartion of the salt is quite tedious!
Hey Nile Red, this was an AMAZING series! I really like the concept and I also feel like you totally nailed it aswell.
Also, thank you SO MUCH for taking the time to purify the paracetamol until it was almost completely white and, furthermore, running an H-NMR to verify the product's identity and purity (at least with respect to organic byproducts); I really appreciated it!
As for what videos you should do; I know it's not on the list, but I think it would be awesome if you could maybe do an exploration of electrochemistry sometime this year... Specifically, I was wondering if it would be possible to produce a volume of water than only contains H2O together with a substantial amount of H3O+ (such as 0.1M or maybe even 1M, without any 'counter ions'). For instance, we know that the electrolysis of pure water produces an acidic environment at the anode and a basic solution at the cathode; so I was wondering if one could use an apperatus consisting of 2 non-conductive containers, each containing an unreactive electrode, which are connected through a relatively narrow, non-conductive tube that has a non-conductive shut-off valve at the center. Then one could simply ramp up the voltage to compensate for the developing overpotential and once the power supply reaches its limit, you could then close the valve, discard the basic catholyte and replace it with either some new, pure water (or perhaps even with half of the acidic anolyte solution)and finally open the valve again and repeat the procedure... Does this sound even reasonably possible, or am I just being stupid again? 😅
How about a capsaicin synthesis?
NITROUS OXIDE
Oxallyl chloride would be neat
Also, adding activated carbon to your refluxing solvent might have discoloured it enough the 1st or 2nd recrystallisation. I'm a huge fan of recrystallisation and I hate running columns but they usually are terrible for your yield.
I also think your product contains a huge amount of water unless your DMSO-d6 was extremely wet, so your actual yield might be even lower.
I love your video's, keep it up!
if you still have some palladium on carbon you can convert vanillin to zingerone via aldolic condensation and hydrogenation, it would be a really nice synthesis, also you could start from eugenol to show how vanillin is industrially produced!
On the first video in the series I guessed 18% yield for the sequence overall. I was a bit too confident in your capabilities, but then you guessed 33%. :-)
Were there any steps in the sequence that could have been done more efficiently by doing multiple steps in one workup? I.e. without cleaning and isolating the product of reaction A, just dump in the chemical to do reaction B.
I have an idea for you to try out. About 25 years ago I came across a bottle of slightly viscous fluid from an old paper manufacturer. It smells kind of strong but not unpleasant, its clear in colour and it bleaches skin like hydrogen peroxide. There is no label on the bottle and I only have about 50ml of it. I kept it just to find out what it is, sometime in the future, but I never did. I can send you a sample and your task is to find out what it is. I can also include another chemical in powder form that also is missing its label. I think it is hydrokinon but i'm not sure.
WGwireless, so, you don't know what it is, but you know that it bleaches skin?
Isn't that somewhat ...wrong?! :P
Extremly wrong. To be honest I got some on my fingers the first time I opened the bottle. When I think about is i must have been more like 28 years ago, still got most of my ten fingers. :P I just remembered that it's not soluable in water and also is heavier than water.
I would love it if you would check your reactions with F254 TLC under some 254nm UV light (you have those in handheld flashlight like form) but I know the plates are expensive
you should make nitrous oxide
I still think a nicotine synthesis or pure extraction process would be a great video. Second choice would be a Caffeine series.
Maybe you could do lidocaine total synthesys for next video series :)
For next video to film, SO3 seems nice ;)
Please keep doing these amazing videos!! I love your experiments! Who else, like me, after watching NileRed's videos, wants to do his experiments?
Nilered could you do the nitrous oxide video and the caffeine complete synthesis?
Can you make a Video about forming rings?
Like forming cyclohexan from hexan.
Now can you go the other way
extract some more essential oils like eugenol from cloves via steam dist. or brew some coffee via shoxlet extraction !
aspirin from willow bark
Why dont u do de reverse way, the industrial Acetaminophen to Aspirin?
Nylon Synthesis please. it'll be a good way to see condensation polymerisation
nitrous oxide
Are you interested in making pyrimethamine? You could compare your work to nurdrage's and it might be for a good cause.
Aspirin from willow bark ! Please, that'd be so interesting ! :'D
i vote for the nylon 6
Caffeine for sure for next demonstration. Great material in this series.
synthesis of nicotine
caffffffinneeeee
I know this is asking for something that is a little different than your normal type of videos but could you make a video explaining the difference between sN1, sN2, E1, and E2 reactions?
Nitrous oxideeee.
Hey Nile, i was wondering if u could make a video about singlet oxygen. You could make a
qualitative video...would be the first on RUclips :D
Oxalyl chloride.
Some suggestions Nile, try doing the carbylamine test, benzene Diazonium chloride coupling reaction with phenol and aniline, please.
WOW!!!!!! Aspirin completion , Nile plz tell me happy birthday even though it's not
Happy birthday!
I liked this series very much Thank you Nile You are the best
CHEM 120L AYYYY
I loved this series! Congrats on finishing it up even though it wasn't efficient!
Some cool ideas would be going back to inorganic chemistry, I find organic stuff a bit dry at times.
Maybe nanopartcles and some electrochemistry stuff.
Gratz on 100k!
It's funny because I am the total opposite. I find that org is lively and inorg can be more dry
NileRed It's a great subject but it's often a bit 'unspectacular' for videos. ;)
organic is nice, if not for the long waiting sometimes, like 6h mixing for example :D
NileRed Thinking about it, you could do the organic dyes if you've not already. Visually cool and relevant to lots of other chemistry.
Can you extract quinine from tonic water?
You can also reduce Vanillin Oxime using Pd/C , NaOH,NaBH4 to turn it into vanillin amime
He said it didn't work for him...
I didn't know that
where did he mention it
Ephedrine synthesis from pseudoephedrine
One vote for oxalyl chloride, the more OTC the better :)
How is the reverse process done, acetaminophen to p-acetaminophenol from Tylenol? As p-aminophenol is a developing agent for photography, this process interests me very much.
As I am in Brazil, getting p-aminophenol is difficult and expensive, it would be good to know how to get this agent in other ways.
Thanks
P.S.: Sorry about my English
Loved the series NR. My vote for next potential synthesis series is a Methylxanthine alkaloid, although not the Caffeine everyone else seems to want. My vote is for
8-Chlorotheophylline, much milder stimulant than 1,3,7-Trimethylxanthine(generally referred to as "caffeine" by the uncultured savages, ;-P)
They only differ by 1 C, 3 H, and 1 CL; and I wonder how much easier or harder that will make the synth, also it's a fairly common additive for reducing drowsiness in OTC anti-emetics that most people are simply unaware of.
Congrats Nile! To complete your first six-stage synthesis to the final product is a big achievement despite of the yield. This indicates that your skill matures. But I think you have to invest into proper glassware for working with small quantities. I bet your supersized funnel with porous filter contributed big time to your 18% yield. Are you acquainted with the techniques of micro scale synthesis by the way? If not I suggest you to. It could help you to reduce losses on the last recrystallization stage.