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.
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 👀
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
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
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.
@@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
@@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.
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.
@@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.
@@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...
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
@@Quinazolinkingas 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
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.
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).
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.
@@bestelevated Then why is it not classified as cancerogenic despite a production volume of dozens of millions of tons per year? "Big Chem"? Benzene contamination in dirty toluene doesn't count
Screw Modafanil, let's just skip straight to a Morphinan structure. ;D Speaking of Modafanil, it doesn't do jack for me. I take a hlf a gram and still have a good night sleep. lol
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
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.
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!
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.
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.
@@durshurrikun150 No... Phenyl groups are highly sterically hindering. Even more so, the reaction is in aqueous solution, which stabilises the carbocation (favours SN1) and solvation of nucleophile disfavours SN2. The substitution site is also secondary, which is even more sterically hindering (disfavouring SN2) and more stabilising of the carbocation (favouring SN1).
@@durshurrikun150 Only when the leaving group is primary - this case is secondary, which is more sterically hindered and stabilises carbocation even more
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
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.
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
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
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)
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.
1:18 Caffeine, in combination with modafinil isn't dangerous. It's just that modafinil increases the effects of caffeine. So if you've been prescribed modafinil, maybe just take half the amount of caffeine you usually take, wait to see how it affects you, and then if you still want more, take more.
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
Love your videos! I would like to ask you to elaborate more on the solvent selections in your videos. Unfortunately, I don't understand why you sometimes use solvent mixtures and sometimes you don't. That would help me a lot, thanks 😊
any particular reason over just buying the active alkaloids? I live in a place where the plants containing the active alkaloids grow like weeds and even the, less than legally minded night walker types, dont seem to bother
@therideneverends1697 probably to try boost the natural concentration of the alkaloid. Bit like how poppies and coca are bred to boost levels of morphine and cocaine.
@@therideneverends1697it depends on the species, some contain only pseudoephedrine which make them pretty pointless aside from making flue remedies, on the other hand a lot of species especially in Europe contain notable level of ephedrine which make them quite active even in tea form. Here ephedra plants can grow really tall and you’ll harvest more than you need easily
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
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.
Patents should be exponentially more and more expensive to renew, so that at some point it's unreasonable to continue to hold them when they are in use.
Patents in any case in most countries completely expire in 20 years. Patent maintaining fees too gradually increase toward end of patent lifetime, but not especially exponentially, though probably you could try to fit exponential curve to that few (law defined) points of increase, if you feel so inclined.
I tried modafinil, it is my favorite stimulant so far. Improves wakefulness, focus and wellbeing with way lower risk of anxiety. I would love to see variation of red bull using their patent however I don't know if i'm ever gonna see it since mega-corporations fkn suck so sadly i think it's just a dead patent.
@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?
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.
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?
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.
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
@@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
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.
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??!!
I think it's called "defensive patents" - They invent something, patent it so no one else can make it, and then they don;t make it themselves... no one can, which help keep them in the business. Also they can sue others who do and make money of it anyway.
Interesting and thanks. If you are going to do a chromatography anyway, you might want to think about putting some wool into the column, as this will separate out the optical isomers. Which means that if you go back a couple of steps you can end up saving yourself some $ and time with solvents and so on. Using wool or maybe unbleached paper is sort of old hat and there's been books and papers endless written about this, so you should be able to adapt your general scheme pretty easily, I think. Used to be a pretty common approach in commercial pharmaceuticals.
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
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.
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
'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
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
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?
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.
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 set up a drinking glass…” haha
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...
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
@@Quinazolinkingas 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.
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 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 was going to say, it has a completely different route than MPH.
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.
@@christiannorf1680 as an ex dmt extractor, nope. Toulene may cause a lot of cancer but heptane won't.
@@bestelevated Then why is it not classified as cancerogenic despite a production volume of dozens of millions of tons per year? "Big Chem"?
Benzene contamination in dirty toluene doesn't count
@@bestelevated Is toluene a carcinogen?
I thought that they replaced benzene with it because it is not a carcinogen.
@@christiannorf1680 Heptane and toluene have fairly similar boiling points.
You can remove them with a rotavapor and a vacuum pump.
Loved that silica gel filtration
I was on board for the sketchy white powder, but peach Lipton is where I draw the line.
whattttt it’s good 😂
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
Please tell me you will be selling samples of what you made in this video soon as well?
Screw Modafanil, let's just skip straight to a Morphinan structure. ;D Speaking of Modafanil, it doesn't do jack for me. I take a hlf a gram and still have a good night sleep. lol
Man, you are, in my opinion the best chemist on the web today. I really loveyour videos!
Thanks for explaining the mechanisms behind the reactions, it makes it more engaging to follow along.
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
I specifically liked how you and your friend tried it so we can have a expectation.thanks a lot
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 as always. Would like to hear more about the pharmacodynamics of drugs you make in the future!
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!
Wow--that desreves a tip!
I'm subscribing.
You explain very good and put the names of the reagents and explain the mechanisms.
I learned a lot! Thank you.
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.
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.
Benzilic positions are very activated towards both Sn2 and Sn1
@@durshurrikun150 No... Phenyl groups are highly sterically hindering. Even more so, the reaction is in aqueous solution, which stabilises the carbocation (favours SN1) and solvation of nucleophile disfavours SN2. The substitution site is also secondary, which is even more sterically hindering (disfavouring SN2) and more stabilising of the carbocation (favouring SN1).
@@thecsslife Yes they are, in general, in this specific case sn1 is favoured over sn2
@@durshurrikun150 Only when the leaving group is primary - this case is secondary, which is more sterically hindered and stabilises carbocation even more
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 😂
15:13 hits my soul
great video! It was seriously cool that you actually tried the drug
don't drink the chemicals you make! pour them in tea first
love to see more drug syntheses
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
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
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
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
Short path vacuum distillation my beloved
Missing: a melting point determination for purity. An HPLC/UV/FL test for presence of trace contaminants. An IR scan for compound ID.
-that chemist
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)
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 🤣
Coffee makes me feel like im going to die.
Adderall or Dexedrine however are smooth sailing
"Otherwise it might explode" all of a sudden made me shoot beer out my nose lmao
😂😂
1:18 Caffeine, in combination with modafinil isn't dangerous. It's just that modafinil increases the effects of caffeine. So if you've been prescribed modafinil, maybe just take half the amount of caffeine you usually take, wait to see how it affects you, and then if you still want more, take more.
Redbull also sells Sodas, like their Redbull Organics line
but im not sure they would use CE-123 in that
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.
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
9:30. I'm not yet into practical, but searching the wiki shows the cumene hydroperoxide as having the peroxide at the bbenzylic position.
What was dropped in at 7:20 ? The magnetic stirrer?
@Chemiolis there is a caffeine-free drink that tastes exactly like Redbull in the GCC region called Super. The Tutti Frutti flavor
Love your videos! I would like to ask you to elaborate more on the solvent selections in your videos. Unfortunately, I don't understand why you sometimes use solvent mixtures and sometimes you don't. That would help me a lot, thanks 😊
Neat that you are making that.
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.
any particular reason over just buying the active alkaloids?
I live in a place where the plants containing the active alkaloids grow like weeds and even the, less than legally minded night walker types, dont seem to bother
@therideneverends1697 probably to try boost the natural concentration of the alkaloid. Bit like how poppies and coca are bred to boost levels of morphine and cocaine.
@@therideneverends1697it depends on the species, some contain only pseudoephedrine which make them pretty pointless aside from making flue remedies, on the other hand a lot of species especially in Europe contain notable level of ephedrine which make them quite active even in tea form. Here ephedra plants can grow really tall and you’ll harvest more than you need easily
Red Bull does sell drinks without caffeine: Red Bull ORGANICS.
absolutely incredible video, chemistry is beautiful.
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
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.
its called the analog act buddy..
Patents should be exponentially more and more expensive to renew, so that at some point it's unreasonable to continue to hold them when they are in use.
Patents in any case in most countries completely expire in 20 years. Patent maintaining fees too gradually increase toward end of patent lifetime, but not especially exponentially, though probably you could try to fit exponential curve to that few (law defined) points of increase, if you feel so inclined.
You forgot the bull semen
You forgot my semen
And my semen
It’s right here he just forgot to mention it: 4:57
And the poor bastid who has to collect it
2:29 urea?
I tried modafinil, it is my favorite stimulant so far. Improves wakefulness, focus and wellbeing with way lower risk of anxiety. I would love to see variation of red bull using their patent however I don't know if i'm ever gonna see it since mega-corporations fkn suck so sadly i think it's just a dead patent.
@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?
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.
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.
Im pretty sure there is caffeine free red bull, Ill check on monday when stores get opened
No, there's sugar-free Red Bull, but there's not a caffeine free version.
Have to be careful with celite it sometimes contains heavy metals.
Is this just your personal lab? Can you do a lab tour maybe? Your lab looks so clean and organized.
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
I didn't see it on the ingredients label
might have to drink another one to make sure
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.
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
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??!!
Now we know where the color of Red Bull comes from
how can cocaine be illegal but we just casually do shit like this and call it taking “smart drugs” lol
Can you make Picaridin(Icaridin) the mosquito repellent?
I'm wondering how cheap it actually is compared to what we can buy commercially.
Can you do an issue on how to extract oxytocin from ergot?
Holy shit why does red bull have a modafinnil analogue patent wtf
The oxidation is btw. a so called Keagan Oxidation. Keagan as the guy modifying the sharpless oxidation.
I have a video idea for you, test the concentration of estrogen in tap water. I really think this could be an interesting video.
If it's a modafanil analog, it's not a stimulant. Wakefulness is not the same as stimulation.
It is a stimulant in the DRI aspect. It is also personally confirmed to have stimulating properties x)
Great work! Im first time at your channel and im your fan!
How much more difficult would it be to make modafinil ?
Fun fact Provigil is the drug the movie Limitless was based off of.
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
oh kay, i wasn't sure, but now that it's done - totally a diy thing :snark:
great video, didn’t know about the compound! that column tho
I'm pretty sure this ISH can be allowed in a drink only in US, not in Europe. Am I right?
Is there any difference between short-path distillation and using a rotavap?
"very achievable synthesis" 😅
Very well of a video, bro!
This is wonderful, thank you 🙏
“ and I don’t fucking hate myself”
Amen brother
I think it's called "defensive patents" - They invent something, patent it so no one else can make it, and then they don;t make it themselves... no one can, which help keep them in the business. Also they can sue others who do and make money of it anyway.
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
9:27 usually when I think of cumene hydroperoxide I think of the intermediate in the cumene process
How about bupropion? Or are the precursors too expensive?
Guy finds patent for niche stimulant and decides to not only make it but to consume it as well. Holy based...
Interesting and thanks. If you are going to do a chromatography anyway, you might want to think about putting some wool into the column, as this will separate out the optical isomers. Which means that if you go back a couple of steps you can end up saving yourself some $ and time with solvents and so on. Using wool or maybe unbleached paper is sort of old hat and there's been books and papers endless written about this, so you should be able to adapt your general scheme pretty easily, I think. Used to be a pretty common approach in commercial pharmaceuticals.
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
Very interesting. you show the target molecule in a pure enantiomeric form so what about chirality of S atom?
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 need my daily stimulant and caffeine just to get out of bed, lmao.
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.
Can you provide any explenation of cicloexane/toluene solidification process?
Where buy the reagenti this guy?