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- เผยแพร่เมื่อ 19 เม.ย. 2024
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Correction: Cumene hydroperoxide structure is wrong (Chemdraw name to structure conversion issue), it should have the hydroperoxide attached to the alkyl.
Synthesis:
pubs.acs.org/doi/10.1021/acso...
Patent:
patentimages.storage.googleap...
Sharpless literature:
www.thieme-connect.de/product...
pubs.acs.org/doi/10.1021/cr04...
www.sciencedirect.com/science...
link.springer.com/chapter/10.... - วิทยาศาสตร์และเทคโนโลยี
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Alright folks, if your interested in a more in depth case effect profile:
( I was the other bloke in the vid who tried the CE-123 )
0:00> 125mg single oral dosage
0:40> I noticed an increase in clarity and awareness, more awake, bit stronger than caffeine would. Fague stimulant alike tendencies.
1:20> More focus on tasks, motivating and subtly calming. Gentle increase in energy is also noted.
3:30> peak effects, this compound would be good for office hours. Can be best compared to a weaker version of R-modafinil but with more dopaminergic response, actions that give rise to a dopamine spike are exacerbated and thus, more enjoyable and satisfying.
A dramatic increase in memory acquisition and retrieval is not particularly noted.
4:00> I’m way more aware now, I’m way more focused ( refrence? xd )
4:30> slow decrease towards baseline, still very functional without being pushing.
This plateau is preferred over peak serum levels thus in the future a lower dosage would suffice. No comedown.
6:00> baseline, no after effects.
Conclusions:
Is this compound one that’ll make you a hyperfunctional CEO millionaire, like selegiline or amphetamine would? Not at all.
However it may have its use in gently providing extra alertness and motivation where caffeine fails.
As far is I noted with this single experience it is side free and does not feel “present” like modafinil or caffeine does.
Not to be repeated personally.
good to know
how long have you been taking modafinil yourself for? I'm curious if you've had built up any tolerance?
Personally, I've been taking it for over 2 years, and I'm not sure whether I've built up a tolerance or not, but I've kept the daily dose the same (100mg modafinil + 75mg armodafinil).
@@Jackson_Zheng Only a few times, I do not really believe in taking any medication for a prolonged period since this will induce changes in cortical tissue which might be permanent.
Modafinil for me is only used sparsely when I have been procrastinating important things such as meetings, company calls etc. and have to finish them all in a day. I would not recommend taking such for a prolonged amount of time without any medical reason 👀
Is this in hours or minutes?
@@evilsanta8585 hours
If patents were invented 2k years ago, we would still ride horses.
Так и есть, патентное право очень тормозит развитие
@@user-arbuzer12 что
@@aciddev_ ничего
@@aciddev_you can easily understand what he said
That is not true. Patenting stuff also requires you to make a very detailed description, which helps others in R&D as patents are often fairly easy to bypass.
There is a fine line between patenting or not, and while it's far from a perfect system, it does work well.@user-arbuzer12
'Since I don't fucking hate myself...' The man speaks truth.
I'd smoke that vial as is..... I don't hate myself.. ha-ha
This is why this drug is always faked.
Who likes cleaning? I feel this guy for sure!
I laughed so hard at that.
Time stap this
while redbull can give you wings, it can also give you patents for chemicals
Or an addiction if you can find the juneberry🫶...the summer one is at only one Walmart near me but it's pretty good other than the fact it's a one and done you're not having multiple a day
@@dimagass7801 Redbull is the only one i cant drink. I taste it in every burp until i go to sleep. the sappiness does not work with my stomach acid
can't wait for "eugeroics i have known and loved" so you will be like Shulgin
But you have too admit that Phenethylamines carry a sertain punch 😅
Xd
@@TheLtVossi love how you spelled “phenethylamines” correctly but not “to”, or “certain” lmao
@@zonkz6947 Dyslexia kicks yoooooo I just dont see it 🤷
Is eugeroics that bad?
“I set up a drinking glass…” haha
Minor point - this isn't patented. What you found is a patent application publication, which is issued 18 mos. after the initial filing (or priority) date. The EPO application was withdrawn (abandoned), along with the Canadian counterpart. The US application is still pending, but if it meets significant resistance from the USPTO, it will likely be abandoned as well (Red Bull seems unwilling to invest significant money in pursuing the application). If/when it gets patented, the document will say "United States Patent" and be assigned an 8 digit number (currently in the 11 million series).
Publications of applications are not enforceable - only patents are.
I’d love it if they added this shit to Red Bull, but the FDA and DEA would throw a fit
@@Sniperboy5551 probably because we know the interactions of modafinil with other drugs (or cardiac conditions) and an analog could easily be safer, or less-safe, fairly in depth studies would probably be needed.
@@Sniperboy5551 I mean, If the company pays them enough money theyll do anything so you can keep your hopes up c: Corporate lobbying always got your back
This guy patents
@@CatgirlExplise6039 it would help but health Canada in particular is *very touchy* about these things, they dont like the high dose caffeine stuff as-is. Tax dollars deal with the results of ill-health so there is a significant federal, provincial and public interest in making sure that red-bull drinkers dont start suddenly dropping like flies with cardiac issues, as our system is already strained beyond capacity.
lobbyists can do alot but if reactions start happening, that stuff will get pulled very fast, rofecoxib is a great example.
I would love to see more in depth studies, as this compound (or yet another analog) will likely exist in some consumer form eventually, and if safe could be very useful for those with a methylxanthine sensitivity that cant leverage the cognitive benefit of coffee for example.
Owning a bottle of Thionyl Chloride is an actual flex
Even I thought it
Wait why is it haha
@@thymenwaterman8672 it's a super powerful reagent, a convenient chlorinating agent that is very hard to get on hand as a private customer. Expensive too.
@@thymenwaterman8672 Controlled substance under the chemical weapons convention, apparently 🤷🏻♀
@@katrinabryce Regulations are stupid sometimes. Last time I ordered sulfuric acid, I had to sign an end-use declaration. I thought they were joking. Apparently because it can be used as a catalyst for making acetone peroxide. Why acetone is not regulated by that logic is beyond me.
Later I also found out that my institution doesn't have the permission required to buy potassium permanganate, which is also super weird. Luckily I found some bottles of old stock...
To realise that I'm actually living in a time where this just happened... and the author linking to a synthesized dose of product available worldwide... what a beautiful moment this day is for me.
Bravo for everything about this... how interesting... this entire situation is brilliant and such a testament to so many things. What a time to be alive.
I love these videos and the way you explicate them including the reaction mechanisms... welcome to the SHORT PATH VACUUM DISTILLATION channel
I've always wondered, why always short path distillation??
@@noobkanon2 Because he does not have rotary evaporator, which is normally used for the rutine solvent distillation
@@ondrejnovak339 I might have one in a few months ;)
No machine has probably revolutionized organic chemistry like rotavaps did. Even more than magnetic stir plates
@@christiannorf1680 You forgot about vacuum distillation
Modafinil’s dopamine reuptake inhibitory effects are known from rat studies taking heroic doses afaik, so I wouldn’t say it’s a DRI. Its mechanism of action at normal doses is still unclear and involves multiple sites, including histamine (H1 & H3) and adrenaline (α1).
I don’t agree, with receptor coupling with target site at DRD2 (PHE76, ILE484, VAL152, PHE326, ILE148, ALA81) there is a clear positive correlation between its dose related effects and affinity.
Also there has been established in multiple papers that the primary eugeroic, stimulant action of CE123 (like (R-)modafinil is directly correlated to the agonism of the sub2 human dopamine transporter. If I remember correctly it has even been studied with cloned basal ganglia dopaminergic receptors.
Furthermore all of its effects like memory aquisition/retrieval, awakeness, motivating, etc. Can be directly connected with dopamine activation
@@Quinazolinekingas somebody with a svt heart condition, I cannot take amphetamines or modafinil without triggering heart palpitations, but I can take coca alkaloids with zero effect on my heart condition.
yeah it's a really weak dri (not even close to mph or amphetamine) but it's one part in its pharmacological profile, quite an interesting molecule though ngl
Gotta love those heroic doses 😂
Yes, this cu#ts dangerous. Do not try this shit punters. Just tell your Dr you seen this shi# and he'll write you up some Ritalin scripts, problem will solve itself. Aint no fun being a guinea pig for some pseudo scientist. Steer clear guys its dangerous and could fuc$ your kidneys and/or heart. There is a reason guys who do know these 'trick' dont put them on youtube its simply click bait fellas. Good on ya mate for setting them right. It takes real empathy to weed these pricks out. Stay safe learn chemistry in a lab not on youtube guy's.
Sonicating in Heptane is typically a much easier way to force an oil to crash out. It also has the benefits of being much less toxic than toluene and a much lower boiling point, so pulling it off is much easier too.
Eh, heptane is pretty much just as toxic as toluene (if you are not a pregnant woman). But toluene smells nicer :) It's true though, removing toluene is a pain in the ass.
Toxicity wise, if you are using chlorinated solvents, there is not really a point in avoiding toluene.
Loved that silica gel filtration
Man, you are, in my opinion the best chemist on the web today. I really loveyour videos!
Modafinil isn't really a dopamine reuptake inhibitor like MPH, it has a unique mechanism of action and also interacts with the orexin pathways.
also modulates histamine release in the thalamus to increase wakefulness
Only source I’ve seen with a good explanation of the Mechanism is Stahl’s essential psychopharmacology
literally every medical text in a decade of pharmacist practice was vague outside the orexin stuff
The dopaminergic activity is SUUUUPER selective to some areas of the brain too
I forget exactly where it’s been a while (knee jerk is thalamus or mesocortical but I cannot remember well)
very true, minimal dopamine interactions. It has a slight effect on dopamine, but that is not it's main mechanism of action(unlike amphetamines, very very different, which is why modafinil is non addictive, can take it daily for months and go fully cold turkey and it won't bother you at all).
NOPE it is a D1 agonist in many parts of the brain it will block the re-up take of dopamine and it is his main mecanism of action
I'm subscribing.
You explain very good and put the names of the reagents and explain the mechanisms.
I learned a lot! Thank you.
Great video as always. Would like to hear more about the pharmacodynamics of drugs you make in the future!
Icilin samples from one of my previous videos are now available for sale chemiolis.squarespace.com/ Only 50 available.
❤
can you provide the 1h nmr result of the product pls :P
bro please make a single video without 4000 hours of stock footage
I bought it, I hope it will be deliverd safe and sound. I'll measure nmr for you)
@@captainchicky3744 I will
btw Im pretty sure the hydroperoxide in cumene hydroperoxide is attached to the benzylic carbon, not the benzene ring. maybe this is some other cumene hydroperoxide that I havent heard of, but "cumene hydroperoxide" generally refers to the benzylic hydroperoxide
You're right, it seems it is an issue with Chemdraw when converting name to structure
Congrats! Your video started my day and gave me motivation to arrange my workspace and if I happen to get the glassware washed you will have at least an anecdotal report of previous video having "stimulant" like effects by just watch ing it first thing in the morning. I'm glad for the selective sulfur oxidation step you described as classical H2O2 method was the slightly annoying part when I made modafinil years ago... also you may know that in the case of the well sold one, a certain crystal lattice is remarkably more potent then the crude stuff I obtained. Even though pure, the potency albeit obvious, it increased significantly after performing a well described method of recrystalization involving some ethyl acetate and some more solvents. I bioassayed it because proton NMR could be agreed with and I can't make any sense of XRD data. I'm sure you might have thought of trying to obtain the derivative starting from bis-(4-Phenyl)-methanol it may be a thing. Cheers!
Neat that you are making that.
Yoooo no way! I mentioned this patent in a modafinil video about a year ago and have kept my eye on it ever since. A energy drink company patenting drugs could be suggestive of a new era of recreational pharmaceuticals.
great video! It was seriously cool that you actually tried the drug
don't drink the chemicals you make! pour them in tea first
Nice, I didnt know this compound existed at all! I'd love to see the med chem rationale between the substitution of the amide for the 1,3-thiazole.
Btw cymene hydroperoxide bears the peroxide moiety at the tertiary alkyl carbon rather than the aromatic one. The benzylic C-H bond is much more susceptible to HAT than aryl C-H, since the resulting radical is delocalized into the ring whereas the aryl radical would not because the lone electron is located in a sp2 orbital which is orthogonal to the delocalized p orbitals.
Missing: a melting point determination for purity. An HPLC/UV/FL test for presence of trace contaminants. An IR scan for compound ID.
love to see more drug syntheses
I feel like a caveman growing different strains of ephedra plants when I see that lmao
Fun fact, Ephedra are conifers (gymnosperms)
You're a gym no sperm.
15:13 hits my soul
great video, didn’t know about the compound! that column tho
awsome syth, i enjoyed watching that,
Great work! Im first time at your channel and im your fan!
Really cool video, love seeing the organic synthesis!
Just a side note, instead of having to column the compound 4 times, as its a solid - wouldn't it be possible to recrystallise it in say, MeOH/DCM? or some other polar solvent?
I think chromatography can give more definitive purity, whereas some impurities can co-crystalize during recrystallization. If I needed something to be close to 99% for a reaction, I'd just recrystalize it. But if I'm going to swallow a significant amount of it, I wouldn't want to take chances to see if that last 1% is a newly discovered carcinogen
@Chemiolis Hey I'm wondering if you'd consider doing a video about phenazone - one of the earliest analgesics/NSAIDs. Wikipedia is terribly thin on the chemical and it seems like something you might be able to synthesize?
I love these topics, so many interesting molecules that have been invented but never officially used. For example the ring-restricted PEAs from norbornane-analogues like Fencamfamine over morpholines like Phenmetrazine and more exotic stuff like Aminorex analogues.
I wonder why they didn't have the plan for some calcium antagonist, they use taurine as a sedative counterpart to caffeine but something that acts more potently on GABA-B or the calcium channels (like e.g. an Gabapentin, Theanin, Picamilon or GABOB-analogue) would have a much nicer effect, for me the taurine in energy drinks causes a very fatigue-like feeling, almost like feeling painfully exhausted, maybe because taurine can cause hyperalgesia as it blocks opioids. I bet others have the same side effect but can't pinpoint it to the taurine.
Btw; it would be very interesting to see simple as it can get DIY methods to make simple esters, amides and similar conversions of easy obtainable molecules like GABA, Theanine, etc.
Did you do any purification after the first step so that you can give a meaningful yield number?
It could just as well be Thiourea and DPMOH
Have to be careful with celite it sometimes contains heavy metals.
Hi there, for now it´s been months scince i started to search for the chemical synthesis of a pheromone called ANDROSTADIENONE from pregnenolone via converting it with aluminium isopropoxide to progesterone and then removing the acetyl group al c17 position but there seem to appear no information about it, and i think nobody has done it before, the other way i thought it could be synthetized is via elimination of alcohol group in testosterone, but ilegal androgens such as testosterone are hard to obtain so you could use DEHYDROPIANDROSTERONE and use a prosses likely similar to the first one
I REALLY enjoy your videos and hope you could make a video talking of this??!!
Looking at 3:13, it should be SN1 mechanism rather than SN2, for three key reasons. 1. Reaction is in aqueous medium (highly polar protic solvent). This stabilises the carbocation intermediate. Solvation shell around Br- disfavours SN2. 2. Phenyl groups are very sterically hindering, making SN2 unlikely. 3. Phenyl groups are excellent at stabilising carbocation intermediate through conjugation.
So the Sharpless oxidation is really only necessary for enantioselective oxidation, but the racemate made with HP is plenty good enough for most applications. Aside from maybe the Thionylchloride this is a pretty accessible procedure
Short path vacuum distillation my beloved
I used to have a prescription for modafinil for ADHD and chronic fatigue. As I also suffer anxiety, Ritalin and Dexedrine were a no go for me, but modafinil was relatively smoother
@Chemiolis there is a caffeine-free drink that tastes exactly like Redbull in the GCC region called Super. The Tutti Frutti flavor
Good stuff! 🤙
That sulfoxidation process is wild. I don't even understand what is epoxidated, and how the sulfide turns to sulfoxide.
That’s alright mate, don’t feel bad… I honestly don’t understand what you just said here 😂
Wow--that desreves a tip!
I was on board for the sketchy white powder, but peach Lipton is where I draw the line.
This could actually be really interesting, just the thought of someone coming up with a new approach to energy drinks/focus drinks. Anything different from the same old copy paste high levels of caffeine mixture nonsense.. It would be really refreshing to see an actual selection of options in this area
By today's standards that would be considered a psychostimulant (which it is) and heavily regulated (which is good considering the possible side effects). Not gonna happen
Very interesting. you show the target molecule in a pure enantiomeric form so what about chirality of S atom?
Can you provide any explenation of cicloexane/toluene solidification process?
Redbull also sells Sodas, like their Redbull Organics line
but im not sure they would use CE-123 in that
Can you make Picaridin(Icaridin) the mosquito repellent?
I'm wondering how cheap it actually is compared to what we can buy commercially.
I tried the patented Concerta which had undesirable effects. For my ADHD I prefer coffee. It helps me focus more. I usually have instant coffee expresso a few a day.
Espresso 🤣
Is there any difference between short-path distillation and using a rotavap?
I wish I had a friend like you 😊
Very good
Are files for the printed parts of the chromatography setup available anywhere? Looks amazing!
How about bupropion? Or are the precursors too expensive?
9:30. I'm not yet into practical, but searching the wiki shows the cumene hydroperoxide as having the peroxide at the bbenzylic position.
Awesome video! Just as a side note, at 9:30 I think you displayed the cumene hydroperoxide molecule incorrectly. The hydroperoxide group is supposed to attach to the benzylic tertiary carbon instead of a carbon on the benzene ring.
that's in the description
what kind of micropipette are you using? I've never seen anything like that before
13:15 separation, i somehow knew this would lead to a big loss, even though I don't understand anything else in this video. I'll have to take your word that working to not have that loss, would have been as much of a pain as you said, since the other 5000 steps you did seemed overwhelming on their own, unless maybe that's what you meant that this whole process is so long and intricate that you just wanted to finish it.
It’s worth remembering modafinil and traditional ADHD meds don’t work in the same place
Methylphenidate and amphetamines are much less selective than modafinil when it comes to where they act
Though in the decade I was a pharmacist I only saw one source with a good MoA for modafinil, though these days we know a lot more about orexin receptor antagonists (and agonists for sleep)
This is only tangentially related, but I noticed modafinil, while similar in effect to amphetamines, had a cumulative side effect profile- namely, after a week or so of daily use, it caused fatigue and brain fog, as one might experience after night of almost-but-not-quite enough sleep. Food for thought. Chew and swallow, perhaps with c123
Is this just your personal lab? Can you do a lab tour maybe? Your lab looks so clean and organized.
It also causes super vasoconstriction. Drank a red bull and got so cold and the veins on my hands were barely visible. Felt like I was dying.
13:00 Do you have any security measures when working with silica? I I have understood it's quite bad for the lungs.
Silica dust (and dust of all silicates) is problematic. The grain size of column silica is too large for it be air borne under normal conditions.
Oh also, what’s that second addition funnel called? It looks really cool!
Maybe try 200mg. That's the typical dose for modafinil I take, so maybe it'll be more effective.
If I had the reagents and equipment, I'd definitly try this synthesis myself.
It is 6x more potent than modafinil
Red Bull does sell drinks without caffeine: Red Bull ORGANICS.
15:09 I felt that.
“ and I don’t fucking hate myself”
Amen brother
This actually seems like an awesome compound, the main issue with modafinil is the stupid long half life, this from literature is 9.3 food faster metabolising
It's just long enough. You're supposed to be awake for 16 hours a day.
@@maestro9765 have you ever had it? It’s drags on so god damn long, I’m not sleeping that night and if I had it that morning. Granted it’s a very metabolism dependent drug but a 2 hour version would be perfect for me, can always take more
Where can I find the likely 3D printed modular chemistry equipment holder? I know it is made with 2020 extrusions.
It’s SmartRack from Better Basics Laborbedarf
Just in time for this to drop, I have to wait so long to get my sleep study it would probably be faster to just build a lab and make this myself instead
What was dropped in at 7:20 ? The magnetic stirrer?
Can I ask why you use short path distillation instead of normal?
So modafinil is a controlled substance but ce-123 isn't? Even considering they do mostly the same thing?
It could be considered a controlled substance under the analogue act.
I think you asked for video ideas once, one I'd have that's similar to this would be bromantane
"very achievable synthesis" 😅
Very well of a video, bro!
oh kay, i wasn't sure, but now that it's done - totally a diy thing :snark:
Where buy the reagenti this guy?
I'm pretty sure this ISH can be allowed in a drink only in US, not in Europe. Am I right?
I have a whole bunch of this Im prescribed it 2x 36mg concerta and 10mg methylphenidate hcl per day
That's awesome I want to use modafinil for focusing on video editing and making music
I have a whole bunch saved up in a little tub It would be nice to know how to extract The chemical
correct me if im wrong, but based on the mechanism of action of this chemical shouldn't individuals who are being treated for depression avoid taking this as it could interfere/cause synergies with depression treatment related drugs?
Yes, esp adhd meds
Idk why you would think that. I'm not watching the whole vid but if it's anything close to actual modafinil, it's completely fine to use with most antidepressants. Just might need to watch for side effects if combined with SNRI's.
Stimmulants and coffein is not that bad. Mostly bp and hearth related risks. So if ur bp is in healthy range, and u got an healthy ekg recently the risk is almost non existing.
I always did really good in it also
9:27 usually when I think of cumene hydroperoxide I think of the intermediate in the cumene process
6:20 me nodding my head as if I know what he's talking about.
I have a video idea for you, test the concentration of estrogen in tap water. I really think this could be an interesting video.
Modafinil precursors are restricted or I'd make myself
The column comment is SO real if youve ever done large columns 😂 one collumn already tests patience sometimes lol
Whaaaat? Sounds illegal to me ....😊
Look forward to it being sold online, then schedule I by DEA fiat. (oops, my bad, already available online)
I've been playing with nootropics since the 70s, but generally shy away from ones that are too dopaminergic....just don't fall into habits of daily use.
So for someone with narcolepsy and already taking dex; this seems like an awful lot of chemistry to create something probably not even a blip on my radar compared to my medication?
I dunno; all these benzoyl compound solutions seems a little bit hazardous for my liking, i think I might pass. Cheers
How do I get it tho
Can you make a research benzo that's legal in your area? I mean, you made barbiturates, so why not. Always wanted to see a benzo synthesis.
Do you have trusted supplier?
There's tons of "legal" research benzos. But most of them are analogues or very similar to prescribable benzos that it really isn't worth it. The main ones being sold online are etizolam, clonazolam, bromazolam, flu-alprazolam, among others. These are just the most common ones I have seen.
These compounds are also found in green apples.
Confused so is ce123 in redbull?
Now we know where the color of Red Bull comes from
does this count as studying for my O-chem exam?
doin good work o7