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Author: Subject: 3,4,5-trimethoxy-beta-nitrostyrene synthesis
trilobite
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[*] posted on 7-1-2005 at 02:02
Yeah right


Persistent? I don't think so. Besides, that is hardly a question of metabolism anyway. To my knowledge there is evidence of the easily-cleaved methylenedioxy bridge actually being behind the neurotoxicity of those compounds. I don't think neurotoxicity is a big deal to anyone sensible with his usage though.
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guaguanco
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[*] posted on 7-1-2005 at 08:59


I would debate the idea that the trimethoxy substitution pattern is intrinsically 'nastier' in some way. Mescaline is one of the nicest and friendliest hallucinogens around.
This isn't a drug forum, so we should probably steer the topic elsewhere...

[Edited on 7-1-2005 by guaguanco]
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VooDooMan
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[*] posted on 7-1-2005 at 12:07
hum


Enima, care to give me alink to that aldehyde to the corresponding nitrostyrene.........IE you said a link or mirror from rhodium, curous becasue I never seen it, You can u2u me too!

thank you
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Rosco Bodine
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[*] posted on 7-1-2005 at 14:24


Quote:
Originally posted by trilobite
Persistent?
That's right persistent
Quote:
I don't think so. Besides, that is hardly a question of metabolism anyway.
If not a question of metabolism , in the general sense what else determines the persistance of chemicals or their "metabolites" residues of whatever sort in the brain ?
I can't recall the citation at the moment but there have been studies showing some interesting similarities between the brain chemistry of some seriously insane persons and the brain chemistry of mescaline fanciers .
Quote:
To my knowledge there is evidence of the easily-cleaved methylenedioxy bridge actually being behind the neurotoxicity of those compounds. I don't think neurotoxicity is a big deal to anyone sensible with his usage though.
Are we talking about acute toxicity , no that's another subject entirely . And mescaline is anything else but a "gentle" drug . That characterization of mescaline is frankly hysterical .
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guaguanco
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[*] posted on 7-1-2005 at 15:11


Quote:
Originally posted by Rosco Bodine
And mescaline is anything else but a "gentle" drug . That characterization of mescaline is frankly hysterical .

Since Mescaline requires higher dosages than some other analogues, more of the chemical is required. So from that point of view I agree with you.
But I've never come across any literature suggesting that that substitution pattern, milligram per milligram, causes any more harm than other similar phenethylamines (which as a whole are probably not the best possible chemicals to be abusing). There *are* reports of other phenethylamines that display unusual levels of toxicity.
I'm not a biochemist, so I'm not up to date on the literature.
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Rosco Bodine
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[*] posted on 7-1-2005 at 16:08


LD50 figures are a long way from the whole story about toxicity and "physical" toxicity and "psychological" toxicity are also two very different matters . Mescaline is one of the drugs which was used to induce psychosis in order to test the effectiveness of antipsychotic medications in a lab setting . Mescaline was chosen for that purpose because it does such an effective job of artificially inducing psyhosis that it can serve as a
sort of lab standard for the study of drugs for the treatment of the naturally insane .
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Mendeleev
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[*] posted on 7-1-2005 at 17:09


In that case any hallucinogen can be said to induce psychosis simply because of the effects. How exactly does mescaline cause psychosis?



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Rosco Bodine
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[*] posted on 7-1-2005 at 17:24


I do not remember all the details of the literature . You will have to do the research to get the whole story . No not all hallucinogens induce "model" psychoses , at least not in ways that closely resemble the real thing . The way in which mescaline does it exactly is something involving the trimethoxy substituent metabolite longevity / accumulation and
receptor sites which can't deal with it .
IIRC that was the explanation , and as similar problem had been identified about the brain chemistry of seriously insane persons . It was a published article in a professional journal , more than one article about this IIRC . Hey , I don't like it either , I'm just telling you what I've read , and you can check it out yourself .
From personal experience , and a whole lot of it , I'd say there is likely something to the correlation , more than just opinion . BTW IIRC this theory had been supported by radioisotopic trace studies .

[Edited on 8-1-2005 by Rosco Bodine]
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Darkfire
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[*] posted on 7-1-2005 at 18:14


Anyone who says mescaline is "gentle" is out of their mind, or have never taken mescaline. At least in a real dosage. Mescaline is incredibly hard, brutal, and awe inspiring. I have never seen or felt power liek that before. Persisting insanity is incredibly true. I took 18" of 5 or 6" thick san pedro and 200mg of crystals i scraped from the jar january 18th of last year. I felt like an alien to this world for MANY months after. My perception changes were emence for 4 or 5 mounths and moderate for a couple more. To this day i dont see the world the same. For the first time in my life it was like i could really see things for what they were. It was horrifiing on one level, enlightening on another. But anything but "Gentle" thats for sure...

[Edited on 8-1-2005 by Darkfire]




\"I love being alive and will be the best man I possibly can. I will take love wherever I find it and offer it to everyone who will take it. I will seek knowledge from those wiser and teach those who wish to learn from me.\" Duane Allman
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Mendeleev
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[*] posted on 7-1-2005 at 18:43


Really? From what people have told me, it makes colors and shapes look cool, and makes you feel much more love.



Trogdor was a man. A dragon man. Or maybe just a dragon. . .
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Darkfire
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[*] posted on 7-1-2005 at 18:50


Thats all true. But 3 smalls things like that cant even begin to describe it. When people ask me what its like i usualy tell them, "Take every adjective you ever heard, and all of them put together dont even come close to describing more than a fleeting instant of the mescaline experiance." Much less the 18 hours of tripping. I mean every adject you can think of describes it. Scary, fun, good, bad, terrible, awsome, amazing, colorful, dark, religous, ... on and on forver...



\"I love being alive and will be the best man I possibly can. I will take love wherever I find it and offer it to everyone who will take it. I will seek knowledge from those wiser and teach those who wish to learn from me.\" Duane Allman
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[*] posted on 7-1-2005 at 19:39


Quote:
Originally posted by enima
There is an article on rhodium (mirror) which has a nice reduction of a nitrosytrene using Al/Hg around 70% yield, for personal use, I'd recommend this.

The trick is to let the Al/Hg type reductions to run until all the al is consume, add heat and reflux if necessary, it seems to also improve yields.


PLEASE< do you have the link or know where this page can be found, I am looking and have had no success, yet!

thank you
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trilobite
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[*] posted on 8-1-2005 at 00:05


Rosco, I'm not saying hallucinogens can give no persistent effects. My point is that it has nothing to do with the metabolite residues in brain, even if it is no unusual idea among urban legends, but more with psychology and the fact that not all things our brains can learn have positive effects. You only need to go through one extreme emotional experience, maybe one filled with undescribably strong fear, to be able to remember a 1/10 or 5/10 version of it later on -- post traumatic stress syndrome is a very good example of this. Many war veterans are well-aware of it too. Any drug can give persistent effects but some might do so more than others, that is something on which I agree with you, it is the mechanisms I disagree of.

Another side of this issue is the fact that as such effects are psychological, they can be better dealt with pre-emptively than those caused by metabolites could be. If one wanted to minimize the risk of various after effects he should try to make sure the surroundings are not such that provoke fear, something which I learned the hard way btw, not just hope that the metabolites won't play a trick on him. This fact actually enables taking responsibility of one's own actions to some degree.;) But then there is also HPPD (google) which is a bit different thing.

All this reminds me of the well-debunked urban legend that LSD should leave crystalline residues in spinal fluid, giving flashbacks upon release.

My point about the methylenedioxy brigde was to illustrate that harmful metabolites are indeed a problem with MD-compounds and that easy metabolism at the ring isn't necessarily a good thing, and even then it is not because of a residue of any sort but the reactivity of the metabolite. Besides, both mescaline and MDA are also metabolized at the amine function, the former by diamine oxidase (sic) and the latter by monoamine oxidase. All these transformations are to make the compounds more water-soluble and thusly more prone to elimination as those metabolites and as different conjugates of those metabolites -- too bad the metabolites are sometimes toxic compounds themselves... like acetaldehyde in the case of ethanol.

But guaguanco is right, this is very off-topic, so enough said. I only have trouble keeping quiet when I hear these theories.;)
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Rosco Bodine
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[*] posted on 8-1-2005 at 07:28


Quote:
Originally posted by trilobite
Rosco, I'm not saying hallucinogens can give no persistent effects. My point is that it has nothing to do with the metabolite residues in brain, even if it is no unusual idea among urban legends, but more with psychology and the fact that not all things our brains can learn have positive effects. {SNIP}
I only have trouble keeping quiet when I hear these theories.;)


Dood ....or Dr. Dood , There is more to heaven and earth than you have dreamt in your "philosophy" . Now I have spoken of good science done involving radiosotope tagging of mescaline and identification of receptor sites in the brain for metabolite studies , and frankly it doesn't get any more damn concrete than that , so let's not get dismissive about "urban legends" versus hard science when that just doesn't sell , except in the counter culture rap about how it's "organic" so it won't hurt you .
My data had zip to do with "psychology" , it was all about biochemistry and hard data derived from profesionally done studies developing measurable results read on instrumentation......not subjective opinion . So I stand by what I say with something from the lab to back it up , and you stand by whatever you want to believe otherwise and we will both be happy :D
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trilobite
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[*] posted on 8-1-2005 at 10:24


Where's the data you speak of, then? I'm very interested.
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[*] posted on 8-1-2005 at 10:58


Vaguely recalling scientific papers is not good enough. We need hard data. Mescalin became the standard hallucinogen by chance, nothing more.



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Rosco Bodine
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[*] posted on 8-1-2005 at 11:34


This is not just some vague recollection of an article I once read . It was significant enough to me that I photocopied the several page long journal article and kept it for years , along with other related information which was gotten rid of along with a lot of lab equipment , during a time when it became inconvenient for me to have those things in my posession . Now I have no reason to mislead anyone . The article can be found at any regional archives at a university having a complete
professional journal collection . It was at least 15 years ago and perhaps even 30 years ago when the article published , and it was an English language journal ,
and it was indexed then , so I am sure it can be found if you are doing research on mescaline you will run across it as one of the more comprehensive works . IIRC it was a grant funded research , but I can't remember any further details . It may even have been a JAMA article , I'm not sure .

[Edited on 8-1-2005 by Rosco Bodine]
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thumbdown.gif posted on 8-1-2005 at 13:35


trilobite, I suggest you look at the David Nicoles research on the neurotoxidity of serotonin releasing compounds, the damage is supposedly related to dopamine oxidation in the serotonin axon. Serotonin reuptake channels supposedly have a high affinity for the dopamine NT. (Message me if you would like the PDFs) He has made several not toxic serotonin 3H releasers, such as MMA and MMAI. (MMA = 3-methoxy,4-methylamphetamine)

Rosco, persistent insanity???? WTF???
sounds like government propaganda, I'd understand HPPD, maybe, and down regulation of the HT-2a receptors. Insanity? no way. Persistent Perception Disorder....yess...
-----
anyway, back to the thread.

Heres the proceedure for the hendry condensation using ammonium acetate as the amine catalyst. It worth noting that substituting this with cyclohexamine would give higher yields as the ammonium acetate catalyst is known give more impurities than other methods.
----
3,4,5-trimethoxynitrostyrene

Place the following in a 2L RBF;

* 250g 3,4,5-Trimethoxybenzaldehyde
* 500ml Nitromethane
* 10g Ammonium Acetate (anhydrous)
Procedure

* Gently reflux for 5-6 hours
* Cool and distill off any residual nitromethane.

If the crystaline mass prevents distillation, remove it by vacuum filtration and use what is collected OR distill off the filtered nitromethane solution to collect an additional crop of crystals (If the crystals are stuck in the flask skip to the next step).

* Add enough boiling MeOH to dissolve the entire mass (If it's stuck in the flask, if not skip this step, filter, and recrystalize once from boiling MeOH)
* Decant, cool and vacuum filter, repeat the recrystalization if the crystals are not a pure yellow color (which they usually are).
----
(IMO I'd recrystallize once again using IPA)
Be sure to keep this nitrostyrene and any nitrostyrene AWAY FROM THE EYES.

Use gloves when handling it.
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[*] posted on 8-1-2005 at 13:50
al/hg


Enima, do you have the procedure from the 345 nitrostyrene to the correcponding amine, via al/hg amalgam, A link or mirror or some thing? I cant find any thing
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trilobite
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[*] posted on 10-1-2005 at 07:18


Yes, the Nichols group works on interesting stuff. ;) The theory about dopamine causing the damage is well-known, what I'm referring to is this recent article:

http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&a...

Rosco: Ok, maybe I'll try to find it some day. I think I've never done a good medical literature search on mescaline. The reason why I remain skeptical is that I've never noticed even the professionals write about something like that either. By the way, the only reason I'm talking about psychology is that to my knowledge the problems caused by mescaline and many other hallucingens (but not all) are usually more of psychological problems than clearly neurochemical. If we were discussing illnessess like schizhophrenia, depression or anxiety you probably wouldn't be denying these viewpoints either. If you faced one of these conditions you would most likely (eventually) see a psychiatrist, who would likely use chemicals as a tool in something that is very much based in psychology.

The article referred to in the abstract above is the kind of evidence I prefer when questions are directly related to the biochemical side, so please keep your guesses about the philosophy of a stranger to yourself. I never said anything about "organic" not causing any harm, otherwise I wouldn't believe in the potential of MDMA to cause neurotoxicity either. To tell you the truth I very much dislike it when people imply harmful or toxic when using the words chemical or synthetic, as opposed to the so-called natural, so your guess couldn't be much worse off.

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[*] posted on 10-1-2005 at 10:33


Trilobite, I am not sure I understood.
It is well-known that schizophrenia and clinical depression & anxiety show distinct changes in brain chemistry, and the drugs one gets to treat them counteract this imbalance. I guess there is this type of depression which is environmentally induced, and the type that is chronic (internal). Anyway, what you speak of is not a a psychological problem, it is an imbalance in brain chemistry causing this, with the neurotransmitters/receptors involved being well-known. The drugs seek to counteract this, while the psychologist readies the patient for the effect...

Having done a years worth of courses on clinical biochemistry, I think it is safe to assume that ALL drugs alter brain chemistry - the question is how long that effect lasts, and how severe the changes are.
Re. mescaline & permanent insanity- I am sure you know a case or two where people never escaped out of their trip?




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trilobite
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[*] posted on 10-1-2005 at 13:11


Quote:
Anyway, what you speak of is not a a psychological problem, it is an imbalance in brain chemistry causing this


Sorry that I missed it, but what am I speaking of? Schizhophrenia?

Quote:
The drugs seek to counteract this, while the psychologist readies the patient for the effect...


I agree about the distinct neurochemical changes and the fact that all drugs alter neurochemistry. But if the patient has to be readied for the effect by a psychologist then there surely has to be also psychological factors involved, don't they? Otherwise one could just skip the psychologist. I don't think you can rule out either of the factors, but I suppose there are different cases, like the chronic depression for one.

My original point is that many psychedelics (and not all, for sure) are primarily harmful not because they are neurological toxins in the chemical sense, but because of the intense psychological effect they have on the user, which is more likely to have a bad outcome when in wrong circumstances, ie. bad trips. Or why is it so, that one can take LSD many times without problems in a safe and reliable environment, but the one time in a completely wrong place results in problems with symptoms of social anxiety and panic attacks? It then takes a few years to recover from, something that happens through gaining understanding of what is it in other people that makes one feel that way. You might call that very complex neurochemical imbalance but I don't think it is the best way to describe the situation, even if it isn't always possible to say if a disorder is purely neurochemical or purely psychological.

Then there is HPPD, which doesn't seem to fall in the same category. To me, it would resemble a neurochemical imbalance more likely than that above. It is also known that psychedelics can trigger schizhophrenia, but to my knowledge they aren't the actual cause for it. But none of these are direct neurotoxic effects, the kind which MDA/MDMA can cause.

Maybe a new thread for this subject would be in order, this isn't organic chemistry anymore!
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enima
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[*] posted on 11-1-2005 at 01:29
Al/Hg


I will have it posted by the weekend, I do not have access to my main pc which has paper. I will upload it as soon as possible.
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[*] posted on 11-1-2005 at 07:46
YES


Quote:
Originally posted by enima
I will have it posted by the weekend, I do not have access to my main pc which has paper. I will upload it as soon as possible.


Thank god for you enima!!
thanx
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[*] posted on 12-1-2005 at 17:17


Quote:
Originally posted by Rosco Bodine
It would be my personal recommendation to steer away from the trimethoxy whatevers and look with more interest at the MDA , MDMA type compounds which are generally more "user friendly" on terms of the benefit versus risk category .
Trimethoxy compounds are persistent psychomimetics , along with being psychedelics , whereas the methylenedioxy group is more easily metabolized and doesn't have the potential legacy effects afterwards involving little problems like long term persistent insanity for example :D



Yeah, right... How come so many morons get interested in PEAS/AMPHS lately?




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