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Author: Subject: Nootropic syntheses -- piracetam etc.
Quince
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Nootropic syntheses -- piracetam etc.

Anyone try to synthesize any of the 'smart drugs' in the line or piracetam, aniracetam, pramiracetam, etc. ? Some of the newer versions are not available for sale yet, and it would be interesting to compare. I've not found any synthesis information. (Note to moderators: these drugs are not illegal and can be bought without prescription, so don't have a heart attack I posted this).
The other issue is of course how one can test for purity of homemade stuff...
It would be interesting if one could derive any of the newer such as oxiracetam, etiracetam,
nefiracetam, levetiracetam, nebracetam, fasoracetam, and rolziracetam, loracetam, and tenilsetam (did I miss any? hard to keep track...) from the cheaply available ones.
BTW, there's very little information on the distinctions between the members of this large group. Any info on that would be appreciated.

[Edited on 4-10-2005 by Quince]

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Quince
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OK, let me start by posting some images of molecular structure. The attachment is a commonly available one.

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Quince
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So, how do I make the three imaged below, if I say have the first one from above?

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Quince
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[I couldn't figure out how to post more than one attachment at a time, and I didn't want to hotlink to the site I ripped these images from.]

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Quince
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I'm especially interested in synthesizing this one, as it's more rare than the other two. As for the rest mentioned in the first post, I haven't found structural information yet.

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Nicodem
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But what exactly do you want to know about these compounds?

Obviously you did not even try to find them. Just find the respective papers where these compounds were first reported. The syntheis is described there. To find the references use a reference database like PubMed.

…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)

Quince
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I should have been more specific: I'm interested in synthesis from OTC stuff (+piracetam).

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transformer
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I cannot get this refference myself but this one is supposed to be very informative regarding the synthesis of Piracetam

Alex Haahr Gouliaev, Jane Binau Mønster, Mette Vedsø and Alexander Senning: Synthetic and Analytical Aspects of the Chemistry of Piracetam-Type Substituted Pyrrolidines. A. Review; Org. Prep. Proced. Int. 27, 273-303 (1995); Chem. Abstr. 123, 169434 (1995).

[Edited on 12-10-2005 by samsung]

[Edited on 12-10-2005 by samsung]

Quince
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Well, piracetam is the cheap one (I just got 1/4 kilo for $10). The most interesting and useful one to DIY would be pramiracetam. The earliest paper I found at PubMed is this: "Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl] -2-oxo-1-pyrrolidineacetamides, including pramiracetam." However, I'm unable to access it at the moment as the university VPN system is not working right on my home machine, so I don't know if there's synthesis information in it. BTW, is it likely that an individual can place an order from a chemical supply company such as Sigma-Aldrich? I'm not sure if I should try, or would they send the cops on me... [Edited on 12-10-2005 by Quince] \"One of the surest signs of Conrad\'s genius is that women dislike his books.\" --George Orwell Quince International Hazard Posts: 773 Registered: 31-1-2005 Location: Vancouver, BC Member Is Offline Mood: No Mood I've attached the paper. The pramiracetam synthesis is item (8) on page 690, using the precursor synthesized above it, item (43). The second reagent used in (8), the N,N-bis..... I did not find anywhere on the internet... Now, (43) itself uses chemicals that would be hard for me to obtain. Looking at the part it contributes to the final synthesis, can't one use the cheaply available piracetam instead?  The attachment is too big, here's the relevant section:  Quote: Ethyl 2-Oxo-1-pyrrolidineacetate (43). A suspension of sodium hydride (57%) in mineral oil, 45 g, 1.07 mol) in tetrahydrofuran (1.5 L) was stirred, and a solution of 2-pyrrolidinone (Aldrich Chemical Co.; 85 g, 1.0 mol) in tetrahydrofuran (200 mL) was added in slow stream). After the hydrogen gas evolution had subsided, the mixture was heated to reflux, and ethyl 2-bromoacetate (Eastman Kodak; 184 g, 1.1 mol) was added dropwise. The mixture was refluxed for 16 h, cooled, and diluted with diethyl ether, 2 L. The resulting slurry was filtered to remove solids and concentrated on a rotary evaporator. The resulting two-phase oil was washed twice with petroleum ether (500 mL) and carefully distilled to yield 130 g (76%) of 43, bp 140-145*C (20 mm). Anal. (C8H13NO3) C, H, N. N-[2-[Bis(1-methylethyl)amino]ethyl]-2-oxo-1-pyrrolidineacetamide (8). A solution of ethyl 2-oxo-1-pyrrolidineacetate (43; 17.1 g, 0.1 mol) in N,N-bis(1-methylethyl)-1,2-ethanediamine (Ames Laboratories; 28.8 g, 0.2 mol) was heated at 100*C with stirring for 16 h, removing ethanol as it was produced. The mixture was concentrated to an oil on the rotary evaporator and was rapidly distilled through a short Vigreaux column to yield 18.6 g (69%) of 8, bp 162-164*C (0.15 mm). Anal. (C14H27N3O2) C, H, N.  Before vulture attacks me here as well: these are not drugs, in North America they are supplements. Has anyone heard of this N,N-bis..... thing? I can't find any other reference. Also, if someone has access to the ftp (I don't, what a surprise!), I can email them the PDF to upload. [Edited on 13-10-2005 by Quince] \"One of the surest signs of Conrad\'s genius is that women dislike his books.\" --George Orwell ChemistryGhost Hazard to Others Posts: 112 Registered: 5-7-2012 Member Is Offline Mood: Supercooled One of the best nootropics out there are 2C-D. However, Rob Portman made it illegal. 2C-D(2,5-Dimethoxy-4-methylphenethylamine) can greatly increase memory. There are no side effects. "Imagination is more important than knowledge" ~Einstein ChemistryGhost Hazard to Others Posts: 112 Registered: 5-7-2012 Member Is Offline Mood: Supercooled I wonder if a new drug that combines the focusing and processing abilities of racetams with the memory enhancing effects of 2C-D can be synthesized. It'll be like NZT 2.0, but in real life! It'll look like this. Would it even be active. Note: The molecule is fake and doesn't exist. "Imagination is more important than knowledge" ~Einstein trip96 Harmless Posts: 16 Registered: 23-7-2012 Member Is Offline Mood: No Mood I am extreemly excited to hear some more ideas on nootropic synthesis and discussion. I read the synthesis for aniracetam on wiki and it isn't simple, but, it's not super complicated either. Check it here: http://en.wikipedia.org/wiki/Aniracetam#Synthesis A sweet way to further this would be to make up new nootropics like the post above. Surely there must be a large audience here for exploring ther realm of noots. Think about it! Where have all the pioneers gone? Dr.Bob International Hazard Posts: 2475 Registered: 26-1-2011 Location: USA - NC Member Is Offline Mood: No Mood  Quote: Originally posted by ChemistryGhost There are no side effects. That statement is naive about any pharmaceutical compound. There are no compounds for which you can give that blanket statement, as most compounds/drugs have side effects within the normal dosage, and all chemicals have side effects at some higher dosage, including water, salt, and sugar. That is not to say that the compound might not have a wide therapeutic window, where the side effects are quite low and tolerable but there is still a useful desired effect. But be real. That said, the chemical N,N-bis(1-methylethyl)-1,2-ethanediamine is the IUPAC name for 2-(N,N-(di-isopropyl)amino)ethylamine, which is the piece that you desire to attach to the piracetam. They are simply making the ethyl ester and then displacing it with the amine. It could be made from Boc-ethylenediamine and acetone via reductive amination or from di-isopropylamine via a few methods, none of which are likely OTC compounds. kmno4 International Hazard Posts: 1455 Registered: 1-6-2005 Location: Silly, stupid country Member Is Offline Mood: No Mood "Piracetam technology" - paper found some time ago, possibly on this forum (but now I cannot find it), available thanks to some Damned User. It can be useful and informative study about piracetam. Attachment: Piracetam technology.pdf (163kB) This file has been downloaded 2267 times Слава Україні ! Героям слава ! Tungsten. Harmless Posts: 2 Registered: 22-11-2010 Member Is Offline Mood: No Mood  Quote: Originally posted by Quince Well, piracetam is the cheap one (I just got 1/4 kilo for$10). The most interesting and useful one to DIY would be pramiracetam. The earliest paper I found at PubMed is this: "Amnesia-reversal activity of a series of N-[(disubstituted-amino)alkyl] -2-oxo-1-pyrrolidineacetamides, including pramiracetam." However, I'm unable to access it at the moment as the university VPN system is not working right on my home machine, so I don't know if there's synthesis information in it. BTW, is it likely that an individual can place an order from a chemical supply company such as Sigma-Aldrich? I'm not sure if I should try, or would they send the cops on me... [Edited on 12-10-2005 by Quince]

Don't even try with Sigma, you have to be a university or a major lab just to get their catalogue.

Good luck trying to find an easy way with any sort of yield for pramiracetam. If you do, I tip my cap to you.

 Quote: Originally posted by ChemistryGhost One of the best nootropics out there are 2C-D. However, Rob Portman made it illegal. 2C-D(2,5-Dimethoxy-4-methylphenethylamine) can greatly increase memory. There are no side effects.

2C-D is psychedelic in nature. Although that may be a desireable side effect to some, it is a side effect.

 Quote: Originally posted by ChemistryGhost I wonder if a new drug that combines the focusing and processing abilities of racetams with the memory enhancing effects of 2C-D can be synthesized. It'll be like NZT 2.0, but in real life! It'll look like this. Would it even be active. Note: The molecule is fake and doesn't exist.

That isn't how your receptors treat drugs. What would most likely result is a strong psychedelic because the amine is being protected by the cyclic amide. This would make the compound less open to being broken down by mono amine oxidase and thus, more potent.
Dr.Bob
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 Quote: Originally posted by kmno4 "Piracetam technology" - paper found some time ago, possibly on this forum (but now I cannot find it), available thanks to some Damned User. It can be useful and informative study about piracetam.

Very interesting paper. The synthesis looks easy and scalable, all of the materials are easy to get except maybe the GHB, which might be a little harder to buy. I wish the preps I got were nearly that clear and simple. I'm used to the Tett. Letters footnote that does not give any experimental details or yields as my usual starting point. That is a really simple way to make piracetam.
dennisfrancisblewettiii
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 Quote: Originally posted by ChemistryGhost One of the best nootropics out there are 2C-D. However, Rob Portman made it illegal. 2C-D(2,5-Dimethoxy-4-methylphenethylamine) can greatly increase memory. There are no side effects.

Sources for its nootropic effects, please.

*in walks a cognitive neuroscientist*

Really, a drug would show excellent affects of learning with learning curve analysis and a comparative study population. This could be done with mice, bugs, primates, and humans. I suspect the more preferential would be mice (or something non-human) as people have different abilities and tempos for which they analyze, interpret, collect, and abstract from information and data.

I know I could just look it up, but I rather see what credible sources you get your views from. But you're telling me a psychedelic is going to help me learn faster? Learn what?

Of the main drugs that I know really help with learning are ADHD/ADD drugs and modafinil-like drugs. Of course, synthesis and usage without prescription would be illegal. But I've wished I had a few containers of modafinil. Many studies have shown the usefulness of modafinil in sleep deprived animals (no, I won't source it; as it's easier to find than 2c-d on the SCI).

[Edited on 17-8-2012 by Genecks]
Nicodem
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2C-D is a codename for 2-(4-methyl-2,5-dimethoxyphenyl)ethylamine. This compound is certainly not a nootropic. Its main biological activity is agonism at the 5-HT2A and 5-HT2C receptor. As far as I know, no study ever demonstrated it having any direct glutaminergic or acetylholinergic activity. Even if it would have any, the 5-HT2A receptor agonism would cause severe psychedelic side effects before any of the nootropic effect could even be noticed.

Perhaps it just some sort of a stupid anecdotal thing. Mild psychedelic effects have some sort of a "sobering effect" on people, which allows for temporary improvement of some cognitive functions. This might have lead some inexperienced people, who used low doses of 2C-D, to claim it has nootropic effects, but in reality this has nothing to do with the effects of nootropics, which are in any case mostly manifested only in demented people. Sane people, with a normally functioning glutaminergic system, generally do not notice any obvious improvement upon nootropics treatment. This is why they are mostly only prescribed to the elderly and alcoholics.

…there is a human touch of the cultist “believer” in every theorist that he must struggle against as being unworthy of the scientist. Some of the greatest men of science have publicly repudiated a theory which earlier they hotly defended. In this lies their scientific temper, not in the scientific defense of the theory. - Weston La Barre (Ghost Dance, 1972)

ChemistryGhost
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http://www.erowid.org/chemicals/2cd/2cd_smartpills1.shtml
http://www.smarternootropics.com/table-of-contents/2c-d/
I couldn't find the report of this person who was using it to study and how it was helping that person remomber more and focus on how each topic and sub-topic related to each other. 2C-D does not function via the glutaminergic system. The nootropic effects might be due to serotonin. I know someone who used low doses of 2C-P for nootropic potential. I think the nootropic may work by releasing serotonin to certain parts of the brain. None of these people had any alcohol. Since research can no longer be done, I guess we'll never know. 2C-D was created by the texas institute of mental sciences. It's 2C-T-4 which has the sobering effects you are talking about. The things you are talking about are mostly cognitive enhancers and a few nootropics. There's a difference between cognitive enhancers and nootropics. Enhancement from cognitive enhancers are only temporary enhances the mind while leaving it worse than before. Cognitive enhancers are toxic. Nootropics can permanently enhance the brain and the better functions the brain obtains doesn't go away even after you stop taking them. What if there was a pill that could make the average person(or even smart people) be even smarter, study even better, remember more things and see how each sub-topic is related to the topic. People use caffeine all the time, but the moment someone takes seregiline or 2C-D, every other person freaks out.

"Imagination is more important than knowledge" ~Einstein
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i have become interested in this nootropic: http://en.wikipedia.org/wiki/Phenylpiracetam

because of its high cost and potency, it looks ideal to synthesize

http://gyazo.com/fe1c460347c8b31665f4e9fb7ffbf92c

that looks like a nice synthesis that is analogous to one of the synthesis of piracetam

does anyone know if it would work though?

Li
ChemistryGhost
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Deprenyl is an interesting nootropic. It has neuroprotective properties and a great antidepressant. Only 1mg is required for a day. Sulbutiamine is another nootropic that works by increasing Vitamin B1 in the brain. It's better able to cross the blood brain barrier than vitamin B1.

[Edited on 27-8-2012 by ChemistryGhost]

"Imagination is more important than knowledge" ~Einstein
SM2
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Honestly, find a connect you trust in mainland and have em mailed. Anything not controlled and treated as a commodity (just like a mylar static bag with label) will usually just go through. You have lots of good advice above. I just don't know if your time is best spent laboriously purifying. The older you get, the more precious time becomes. Personally.

There is that old book that kicked it all off by Dirk Pearson and Sandy Shaw (MIT grads) called Life Extension. Many of the tenants in the book have been called into doubt, and then bolstered, only to be called into doubt again, later. Intuitively, I believe a reason the data on the overall beneficiality of anti-oxidants is mixed (at best), or even negative, relating to the body receiving massive anti-oxidants, (when we have our own endogenous anti-oxidants and get a potent mixture of tiny amounts which act synergically). Then you turn on the blunt spigot of something with activity, in huge amounts. It's all very blunt. And through negative feedback (just as with taking opioids chronically), and the body, almost always trying to maintain homeostasis, it's no wonder taking relatively large amounts of 2-3 nootripics/anti-oxidants, and the body will shut down or lower it's own production.

Just something to consider when trying to use a well intentioned sledgehammer on a very sophisticated and finely tuned system. Think of your body as one of the most elaborate organic synthesis setups.
ChemistryGhost
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What about sesamol? It can protect the brain from free radicals and is an excellent antioxidant. Sesamol is neuroprotective. Sesamol in combination with other nootropics may be harmful or fatal.

"Imagination is more important than knowledge" ~Einstein
dennisfrancisblewettiii
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Tell you what I think as a cognitive neuroscientist.

If a drug works as a nootropic or gives people some form of enhanced cognitive ability, then scientists will more than likely be interested in doing experiments with it. That does not always mean they'll be able to get approval for medical studies, however. But if there is some truth to them being nootropes, then providing studies showing that the sample population had increased cognitive ability over the control will do well enough to make a synthesis and self-experimentation worthwhile.

Hence, me being interested in modafinil-like drugs. They add cognitive ability.

I'm an unusual in person in that I've been diagnosed with ADD. So, I'm different from a lot of people in how I will re-act toward a drug. I mean, I've tried focalin for some time, which does great but gives me a next-day burn-out feel (not a great amount, but enough to slow me down and average out my work efficiency). I've considered trying methamphetamine to see how I would react to it. Maybe it would help me focus wayy more than I could have ever imagined. Yeah, I classify ADD as a person who wants to focus but can't manage to focus despite the really strong desire to focus.

[Edited on 9-9-2012 by Genecks]
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 Sciencemadness Discussion Board » Fundamentals » Organic Chemistry » Nootropic syntheses -- piracetam etc. Select A Forum Fundamentals   » Chemistry in General   » Organic Chemistry   » Reagents and Apparatus Acquisition   » Beginnings   » Responsible Practices   » Miscellaneous   » The Wiki Special topics   » Technochemistry   » Energetic Materials   » Biochemistry   » Radiochemistry   » Computational Models and Techniques   » Prepublication Non-chemistry   » Forum Matters   » Legal and Societal Issues