Sciencemadness Discussion Board - 3,4,5-trimethoxy-beta-nitrostyrene synthesis

3,4,5-trimethoxy-beta-nitrostyrene synthesis

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yogi - 29-12-2004 at 13:34

Im looking for synthesis routes for 3,4,5-trimethoxy-nitrostyrene.
The more routes the better. Can anyone help? i know of the spath method mentoined by the MIA Rhodium, but that dates back to the 1919, and also offline.
There must be better ways...

[Edited on 29-12-2004 by yogi]

This should help

Joeychemist - 29-12-2004 at 13:54

3,4,5-Trimethoxy-beta-nitrostyrene

"The following components were placed in a one-necked 1000ml conical flask equipped with a Dean-Stark water trap (capacity about 30ml): 3,4,5-trimethoxybenzaldehyde (98.1 g, 0.5 mol), dimethylammonium chloride (81.5 g. 1 mol), nitromethane (300ml), toluene (300ml) and anhydrous potassium fluoride (4.36 g, 75 mmol). This mixture was vigorously refluxed with stirring for 5 h. The reaction flask was cooled down, then fitted to a rotary evaporator to order to remove the volatiles by gradual heating under reduced pressure. To the tepid residue (~55°C), chloroform (125 ml) and 0.2 M HCl (400 ml) were added. The mixture was heated on the water bath until complete dissolution. Then the flask was stored overnight in a refrigerator (-5°C). A crystalline solid was filtered out by suction, carefully rinsed with water and thoroughly dried in a vacuum oven. The filtrate was poured into a separatory funnel, the layers were separated and the aqueous phase was extracted with chloroform (3x100 ml). The organic extracts were combined then evaporated to give a crude oily material, which was chromatographed over silica gel (400g, eluent dichloromethane-ethyl acetate, 95:5). After removal of the solvent, the resulting solid and the previously separated product were recrystallized together from isopropanol: yield 99.2g (83%); mp 125.5-126.5°C (allotropic change at 121-121.5°C)."

Rosco Bodine - 29-12-2004 at 14:07

There is a much easier way . Heat your nitromethane up and dissolve into it your trimethoxy benzaldehyde , adding some denatured alcohol if necessary for all to go into solution . Add a few ml of butylamine , seal the vessel and incubate it for several days . A layer of water will separate and float on top the mixture . When the layer of water ceases to increase , the reaction is finished . On cooling the nitrostyrene will crystallize and may be filtered . If it is the amphetamine analogue of mescaline which is your intended end product and a better investment of time , then substitute nitroethane for the nitromethane , and your intermediate product will be a nitropropene instead of a nitrostyrene .

yogi - 29-12-2004 at 14:17

Rosco, do you have refs for that incubatioin method?
Also at what temps to incubate? what atmpspheric conditions are needed? etc.. etc...
a ref would be very nice

thankx for all the info guys.
This place is starting to feel like a nice home for this refuge bee....

Rosco Bodine - 29-12-2004 at 14:29

The method is journal published but I don't have the citation handy . One reference was in regards to an electrochemical reduction of methlyenedioxyphenylnitropropene to MDA , in an acetic acid and alcohol electrolyte with a small amount of HCl ,
in a porous cup with water cooled lead sheet cathode , surrounded by an anolyte
of dilute H2SO4 and a sheet lead anode .
I can confirm the method works for the condensation of piperonal and nitroethane . Also can confirm the method works for plain benzaldeyde and nitroethane . The method is general so I'm sure it is referenced several places .

BTW ,
The iron / HCl reduction of the phenylnitropropylene to the phenylacetone is 90% efficient but requires superb mixing equipment , rapid reversing counter-rotational stirrer to keep the iron filings in suspension and the reaction mixture emulsified while the phenylacetone product steam distills .

[Edited on 29-12-2004 by Rosco Bodine]

trilobite - 29-12-2004 at 14:39

Never forget PIHKAL.

http://www.erowid.org/library/books_online/pihkal/pihkal096....

yogi - 29-12-2004 at 14:45

u r of great help Rosco.
Have you heard of the simple condensation of a benzeldehyde in nitromethane with ammonium acetate as a catalyst? It seems also as good., though again refluxing of the volatile nitromethane is needed.

trilobite - 29-12-2004 at 14:53

But that's why you should be refluxing it under a condenser and not evaporating in an open flask.

Rosco Bodine - 29-12-2004 at 15:06

Any time you see lithium aluminum hydride and ether , understand that you can get the thing you are trying to make with less complication than trying to avoid trouble obtaining such reagents as are highly suspect and highly watched , as well as damn expensive .

BTW , refluxing nitromethane is not safe .

[Edited on 29-12-2004 by Rosco Bodine]

trilobite - 29-12-2004 at 15:16

Then there's the cold way of doing the Knoevenagel condensation where the benzaldehyde is dissolved in the nitroalkane, some amine catalyst added, and the mixture kept in a stoppered bottle for a couple of weeks pipetting the formed water out from the bottle now and then. However, I haven't got any details and 3,4,5-trimethoxybenzaldehyde is known to be the picky one.

Rosco: Are you implying that distilling nitromethane is not safe? That's known to not be true as many people have distilled their nitromethane in the past.

Rosco Bodine - 29-12-2004 at 15:25

Quote:

Originally posted by trilobite
Then there's the cold way of doing the Knoevenagel condensation where the benzaldehyde is dissolved in the nitroalkane, some amine catalyst added, and the mixture kept in a stoppered bottle for a couple of weeks pipetting the formed water out from the bottle now and then. However, I haven't got any details and 3,4,5-trimethoxybenzaldehyde is known to be the picky one.

You need to incubate the mixture like I said , 60 C is good .

Quote:

Rosco: Are you implying that distilling nitromethane is not safe? That's known to not be true as many people have distilled their nitromethane in the past.

Nope , I'm not implying anything , I'm saying it straight out , and I knew I'd get an argument . Anybody who want's to reflux and distill the stuff is welcome . I have too , and I'll never do it again because of the autooxidation potential for explosion in distilling a monopropellant which sooner or later catches up with you when you did not plan on it .

trilobite - 29-12-2004 at 16:33

I'm not looking for an argument. This is a matter of theory vs. practice, theoretically it can happen, in practice people really do seem to get away with it. It's something you could argue over forever, quite pointless. However, I can explain my point of view.

In those chemistry boards which are not involved with explosives but the chemistry this thread deals with, the concensus among respected people has been that nitromethane can be distilled safely, as numerous people have done so, that's all. Maybe it can be different if glassware/nitromethane/whatever is contaminated with the right material and you distill to dryness or something. I'm not the person to ask about materials that sensitize nitromethane, I know that microscopic glass spheres can do that though.

yogi - 29-12-2004 at 16:47

I belive nowadays fiddling with nitromethane if possible should be avoided. Technology has evolved a great deal in the last years, and new ways to make anything are popping up like mushrooms after the rain.
Still I accept that while refluxing nitromethane and the likes *could* be dangerous, it is often used and with no dire consequensces.
On the topic at hand - relfuxing with nitromethane is possible, but patience is a virtue, and I like rosco's view.
So ne way, to make a long story short, i believe some1 will try to incubate the Benzeldehyde with nitromethane in the future and report it

Rosco Bodine - 29-12-2004 at 16:58

Let me put it this way . Just because something has a boiling point and can be distilled doesn't necessarily mean that it is a benign material under distillation conditions . Isopropyl nitrite and methyl nitrate can also be distilled , probably nitroglycerin as well , and even though you can get your glass really clean and your vacuum high , sooner or later you are going to get a big and loud surprise .
It is that way with nitroparaffins too . I have seen it happen . It is simply a matter of time .

HRH_Prince_Charles - 29-12-2004 at 17:03

Does anyone know of NM exploding during distillation? I haven't heard of this happening.

Darkfire - 29-12-2004 at 20:18

Keep the temps under control and youll be fine, a vacume could help. Ive never had a problem at atmospheric pressure.

enima - 3-1-2005 at 14:57

Well, there are sooo many wonderful routes...
where to begin?

lets go for the benzaldehyde first.
here are a few methods.

1. Vanillin
a. brominate with NaBr/Oxone, or a NH4Br /H2O2 system for aromatic rings, should have nice high yields.
b. react with NaOH in N2 env to produce the 5-hydroxyvanillin and then react with 2 molar of trimethylphosphate (TMP)
b-ii . do a nucliophillic substition of the 5-bromo with NaOCH3 and then perform a alkylation with 1 molar of TMP and a base.

2. Starting with anisaldehyde, dibrominate the molecule using a really strong system, the FeCl3 (20% molar), NBS (2molar) 1 molar of the anisaldehyde in a CH3CN solvent, stir for a few hours. Evaporate solvent.

b. React with 2 molar of NaOCH3 to do the nucliophillic substition.

3. Starting with elemicin, react with KOH at 140-150C to produce the isoelemicin.
b. React with KMnO4 to produce the benzaldehyde.

From here you can proceed with the typical hendry condensation using an amine, methylamine, butylamine, cyclohexamine in IPA or someother solvent, equal molar amount of nitromethane (maybe 10% extra) and reflux for 5-6 hours.

Recrystallize and you have you product.

Sorry I do not have the time to go into detail, if you would like a more detailed description on any one of the proceedurees feel free to ask. the 3,4 are the safest routes as methylating agents are carcinogenic.

Darkfire - 3-1-2005 at 15:41

From the TMBA with NM MeNH2 NaOH and an HCl dehydration works very well, from begining to filtering your product is less than an hour. No reflux or anything.

Mephisto - 3-1-2005 at 15:53

enima: Do you have a reference for 1b? The mono-methylation of syringaldehyde with TMP to TMBA is shown in US4453017, but I was always unsure if TMP is strong enough to di-methylate 5-hydroxyvanillin directly to TMBA, like DMS can do.

Sergei_Eisenstein - 4-1-2005 at 00:16

Quote:

2. Starting with anisaldehyde, dibrominate the molecule using a really strong system, the FeCl3 (20% molar), NBS (2molar) 1 molar of the anisaldehyde in a CH3CN solvent, stir for a few hours. Evaporate solvent.

b. React with 2 molar of NaOCH3 to do the nucliophillic substition.

Dibromination of anisaldehyde usually is a slow reaction. What they usually do is to dibrominate p-hydroxybenzaldehyde and methylate after the alkoxylation step. Also, it is better to use more than 2 molar alkoxide. Generally, a 3 to 4-time molar excess per bromine is advisable.

For the Henry condensation reaction of 3,4,5-trimethoxybenzaldehyde with nitromethane, I suggest the procedure written out by Shulgin in PiHKAL. It works as described.

example of alkylation with tmp

enima - 4-1-2005 at 11:41

In a three-neck flask (capacity 100 ml) equipped with a mechanical stirrer and reflux condenser, 5.00 g (0.033 mol) of vanillin and 5.00 g (0.036 mol) of anhydrous potassium carbonate were placed and the mixture was heated under a nitrogen atmosphere to 85° C. The mixture was a clear to amber melt of vanillin with carbonate in suspension. To this mixture was added 5.00 ml (0.043 mol) of trimethyl phosphate over about 5 minutes while maintaining the reaction temperature below 125° C. The mixture was maintained at about 80° C. for one hour and then cooled to 40° C. The mixture was poured into 20 ml water and extracted two times with 20 ml of methylene chloride. The combined extracts were dried over anhydrous potassium carbonate, filtered, and concentrated to give 5.4g (99%) of veratraldehyde as a pale oil.

-----------
*keep in mind you need double the tmp amount for your the two hydroxy groups.

Blind Angel - 4-1-2005 at 16:56

Btw, anyone know the best method to reduce the nitrostyrene to the corresponding ethylamine? CTH/Catalyst(Pd/C) or Al/Hg? Which one has the best result, and also a work-up or a good link would be very welcome.

Darkfire - 4-1-2005 at 17:22

Hg/Al is the simpler and more easily acessible choice for a small scale synth.

Borohydride to open up the double bond and catalitic hydrogenation to the ethylamine is higher yeilding, and better for a large scale synth.

Al/Hg gives good yields.

enima - 6-1-2005 at 14:36

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.

Rosco Bodine - 6-1-2005 at 22:13

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

Yeah right

trilobite - 7-1-2005 at 02:02

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.

guaguanco - 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]

hum

VooDooMan - 7-1-2005 at 12:07

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

Rosco Bodine - 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 .

guaguanco - 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.

Rosco Bodine - 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 .

Mendeleev - 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?

Rosco Bodine - 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]

Darkfire - 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]

Mendeleev - 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.

Darkfire - 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...

VooDooMan - 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

trilobite - 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.

Rosco Bodine - 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

trilobite - 8-1-2005 at 10:24

Where's the data you speak of, then? I'm very interested.

HRH_Prince_Charles - 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.

Rosco Bodine - 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]

enima - 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.

al/hg

VooDooMan - 8-1-2005 at 13:50

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

trilobite - 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.

---
I can't decide which culture is the more irritating one, the counterculture or the counter-counterculture.

chemoleo - 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?

trilobite - 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!

Al/Hg

enima - 11-1-2005 at 01:29

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.

YES

VooDooMan - 11-1-2005 at 07:46

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

Sandmeyer - 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

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

Rosco Bodine - 13-1-2005 at 19:18

Here's a thought . Are prions toxic ?

Blind Angel - 13-1-2005 at 19:35

Not alls according to wikipedia, some are native in the cell some are external.

Quote:

The reason prions are not detected by the immune system is that their "safe" form is already present from birth in the body. The only distinction the "dangerous" prions have is that they are folded slightly differently.

http://en.wikipedia.org/wiki/Prion

Rosco Bodine - 13-1-2005 at 19:50

I guess the point I am trying to make is that there are compositions of matter which are ultimately harmful , but that harm does not arise from direct toxicity , nor is it any way related to psychology .

Darkfire - 13-1-2005 at 20:47

The vast majority of mescaline is NOT metabolised by the body, well over 90% passes through without any change. So seeing as only <10% of a active dose will be metabolised, i see problems in assuming the matabolites of a dose inactive by over 10 fold are somehow active enough to cause the long term effects i have noticed.

enima - 14-1-2005 at 07:29

Rosco, maybe you need to look into receptor down regulation, all 5HT-2A antagonist that are considered hallucinogenic have the potential for your so called "insanity" it has nothing to do with the molecular structure of mescaline.

Darkfire - 14-1-2005 at 14:13

His logic is flawed, but it does have to do with its molecular structure, if its structure was H2O, the effects would be diferent. As far as PEA's go mescaline is diferent, as its dose is 10 to 100 times larger than the doses of other PEA's.

Rosco Bodine - 14-1-2005 at 21:20

There you go , its the loading density of the dosage with the trimethoxy group that's the problem with mescaline , and that's because the phenethylamine group is a lousy complement which creates the need for the high dosage . The amphetamine ,( phenylisopropylamine ) or methamphetamine structure would provide enhanced effects and lower risk to the receptor sites simply because of the much decreased dosage required , even with the higher toxicity , that should hold true for the reduction of long term risks . But still in that regard , MDA or MDMA would be less hazardous ....and BTW my logic isn't flawed and neither is my information , unless the study I am getting this from was bogus , which seems doubtful in a peer reviewed journal . You fellows can believe whatever you like about metabolic angles , toxicity , psychology and whatever else you think makes mescaline cool and harmless . It isn't . And the inference from the data I saw was that it can screw up the body's mechanism for managing of natural levels of trimethoxy or methoxy groups in general from whatever dietary or metabolic processes they arise . It sort of reminded me of the analogy where you might give someone who doesn't have diabetes insulin and artificially create a diabetic as a consequence , although that is probably too simple an analogy , it was something like that . So please , do more reading before you dismiss the notion that certain chemicals are capable of causing long term imbalances and dysfunctions in delicate brain chemistries , while attributing any bad user experiences to pre-existing problems or other factors which in many cases simply isn't so . Mescaline can make a fried egg of a brain just like acid can , so there , unfry the egg , and good luck .

enima - 15-1-2005 at 14:15

A Few words to consider.

Brain blood barrier.
Methyl groups, monoxidase enzymes less effective at metabolizing chemical. Increased potency.
----
The long term effects of the hallucinogens are related to receptor down regulation, but MDMA is much worse, I'd rather deal with receptor down regulation than axonal damage as down regulation can fix itself much easier. Granted yes, because mescaline has LONGER DURATION, the down regulation effect is much more. It has NOTHING to do with the dose of the chemical ABSOLUTELY NOTHING. It has NOTHING to do with the molecular structure either .

I will agree with you on the following. The HPPD caused by mescaline is longer lasting than another other natural psychedelics, and this is because of the duration of the drug, (16-20 hours depending on dose). LSD last around 10-12 hours). You will find that individuals who continously use the DOX series (highly potent amphetamines, as you know, which have very small doses) last ~24 hours, also experience HPPD. By no means due these compounds cause long term insanity, IMO this is dependendent on the stability of the individual using these compounds. (FYI HPPD is more prevelent amoung people with preexisting anxiety or depression) Other short lasting substances such as DMT cause servere HPPD but this is due to their high affinity towards the 5HT-2A receptors.

MDA is a strong 5HT-2A inhibitor and while killing off serotonin axons, it is also causing down regulation, resulting in the same HPPD.

Now on the topic of actual "insanity," unlike most other psychedelics which inhibit the 5HT-2A receptors (which actually makes these receptors fire) Mescaline in addition causes an increase in the amount of dopamine. So now you have effectively perceived low levels of serotonin, and high levels of dopamine, which setup a nice chemical model for schizophrenia. (schizophrenic type delusions occur at high doses of any psychedelic drug). Through this I can see how it would seem more likely for an individual using mescaline to go off the deep end, but there is no actual research and thus no conclusion can be made. (Unless of course you have documents that you would like to share with us).

Darkfire - 15-1-2005 at 16:43

The whole MD(M)A killing cells is ridiculas. Normal doses of MDMA or MDA will not cuase damage to the cells. Nueroadaptation is responcible for shutting down or removing re-uptake pumps in the cells, after prolonged usage of MDMA but once use stops the brain returns to normal.

Sandmeyer - 15-1-2005 at 17:02

Quote:

Originally posted by Rosco Bodine
There you go , its the loading density of the dosage with the trimethoxy group that's the problem with mescaline , and that's because the phenethylamine group is a lousy complement which creates the need for the high dosage . The amphetamine ,( phenylisopropylamine ) or methamphetamine structure would provide enhanced effects and lower risk to the receptor sites simply because of the much decreased dosage required , even with the higher toxicity , that should hold true for the reduction of long term risks . But still in that regard , MDA or MDMA would be less hazardous ....and BTW my logic isn't flawed and neither is my information , unless the study I am getting this from was bogus , which seems doubtful in a peer reviewed journal . You fellows can believe whatever you like about metabolic angles , toxicity , psychology and whatever else you think makes mescaline cool and harmless . It isn't . And the inference from the data I saw was that it can screw up the body's mechanism for managing of natural levels of trimethoxy or methoxy groups in general from whatever dietary or metabolic processes they arise . It sort of reminded me of the analogy where you might give someone who doesn't have diabetes insulin and artificially create a diabetic as a consequence , although that is probably too simple an analogy , it was something like that . So please , do more reading before you dismiss the notion that certain chemicals are capable of causing long term imbalances and dysfunctions in delicate brain chemistries , while attributing any bad user experiences to pre-existing problems or other factors which in many cases simply isn't so . Mescaline can make a fried egg of a brain just like acid can , so there , unfry the egg , and good luck .

Get yourself familliar with the meaning of the words: "hazard", "toxicity", "risk"etc before starting these discussions. Move out of the united states, try to adopt some other mentality, stop using methamphetamines and get yourself another hobby.

Geomancer - 15-1-2005 at 17:07

Relating to the original topic (almost): Why not do something interesting, like assembling the ring from scratch. The layout of those oxygens is just so tempting. Friedel-Crafts anyone? Or some sort of enolate type thing? Sure, it may not be as practical, but since when was this board dvoted to practical chemistry?

Rosco, or anyone who knows: I really would like to know more about those studies you mention. U2U if you don't want to stir up the riffraff

. At the moment the avenues I would choose for finding the stuff myself aren't available to me. Are there any reviews regarding the chronic toxicity of simple PEA derivatives?

Also, I'm somewhat skeptical of the claim that permanent brain damage can occur without either histologic or anatomical changes.

Chemoleo: You state that "It is well-known" that various mental disorders "show distinct changes in brain chemistry". This is true. It is not, however, known (and would be very difficult to prove) that this "imbalance" causes such disorders. Indeed, regarding "psychology", it is well known, if underappreciated, that behavior and experience can alter not only brain chemistry, but histology and gross anatomy as well.

Rosco Bodine - 15-1-2005 at 17:11

Quote:

Originally posted by enima
A Few words to consider.

Brain blood barrier.
Methyl groups, monoxidase enzymes less effective at metabolizing chemical. Increased potency.

Brain blood barrier is very easily crossed by mescaline sulfate .

Quote:

----
The long term effects of the hallucinogens are related to receptor down regulation, but MDMA is much worse, I'd rather deal with receptor down regulation than axonal damage as down regulation can fix itself much easier. Granted yes, because mescaline has LONGER DURATION, the down regulation effect is much more. It has NOTHING to do with the dose of the chemical ABSOLUTELY NOTHING. It has NOTHING to do with the molecular structure either .

It has EVERYTHING to do with molecular structure , especially the substituents on the benzene ring and the position of methyl groups on the side chain . What do you think makes MDA different from Benzedrine except for the methylenedioxy substituent on the benzene ring . Duh , structure is EVERYTHING , EVERYTHING , EVERYTHING .....understand ?

Quote:

Now on the topic of actual "insanity," unlike most other psychedelics which inhibit the 5HT-2A receptors (which actually makes these receptors fire) Mescaline in addition causes an increase in the amount of dopamine. So now you have effectively perceived low levels of serotonin, and high levels of dopamine, which setup a nice chemical model for schizophrenia. (schizophrenic type delusions occur at high doses of any psychedelic drug). Through this I can see how it would seem more likely for an individual using mescaline to go off the deep end, but there is no actual research and thus no conclusion can be made. (Unless of course you have documents that you would like to share with us).

I know more about what I'm saying here with documents not in hand than all the bullshit you are talking , Mr. Molecular Structure means NOTHING . Molecular Structure means nothing huh ? Pardon me . In your world , whatever planet you are on , for sure dosage means nothing if the molecular structure means nothing either . This would be just plain hilarious if you weren't serious about your pseudoscience and what you try to pass off for knowledge . But in your mind this actually makes sense , and there's the problem . Have you considered the failed regulatory mechanism which accounts for bipolar disorder , that condition where the brain chemistry never has a stable median state , but swings like a pendulum driven endlessly in over correction , like an inexperienced driver
who can't seem to counter steer into a skid and regain control ? Have you ever thought that just maybe , insulting a delicate regulatory balance in the brain chemistry can throw it into endless overcorrection convulsions , which then subsequently results in physical damage that is permanent ? Well maybe it's not a theory that it can happen just like that . Just like coke can induce a heart attack in a young person with no coronary disease . Psychedelics have similar potential for causing mental disorders , and some of them have more of that potential than others , for reason of their molecular structure , and their dosage . Is there by any chance a medical doctor in the house ? This is actually a topic that would better be addressed by a medical doctor , possibly a pharmacologist , not a psychologist or psychiatrist , but someone versed in chemistry and biochemistry . Better yet , how about a pharmacologist with a second degree in endocrinology .

Rosco Bodine - 15-1-2005 at 17:15

Quote:

Originally posted by Sandmeyer
Get yourself familliar with the meaning of the words: "hazard", "toxicity", "risk"etc before starting these discussions. Move out of the united states, try to adopt some other mentality, stop using methamphetamines and get yourself another hobby.

I don't use drugs , nor do I drink . Maybe that accounts for my depth of discerning being like the ocean , while yours is like a bird bath .

Sandmeyer - 15-1-2005 at 17:20

This energy and time that you waste typing line after line of egocentric nonsence could be directed to open a book and study organic chemistry...

[Edited on 16-1-2005 by Sandmeyer]

Rosco Bodine - 15-1-2005 at 17:24

It's obvious I am wasting my time here .
And I'll leave it with you experts okay ?
See ya .

enima - 15-1-2005 at 17:48

Wow some intellegent individual you are resulting to personal attacks which I assume are easy to do behind a computer.

Yes obviously molecular structure is going to play a role in the alteration of chemistry of the brain, otherwise chem a or chem b of different structures would do the same. I was simply stating that the hppd effects are caused by receptor down regulation. It is a current running and most logical theory (IMO) at the moment. I think you lack the ability to understand what I was trying to get across. It is the function that occurs (obviously attributed to the structure) that brings on the results, not just the structure. Consuming psilocin at high doses and at a period that would give similar duration periods to mescaline and concurrently using an amphetamine would result in similar hppd.

Mr. MDA is safer than mescaline, excuse me, MDA is more TOXIC than MDMA. Why don't you look up the data, its all in the journals.

You knowledge of brain chemistry seems very limited. Please do not attempt to give me your 1920's bullshit. What next? you are going to tell me that mescaline works by depriving the brain of oxygen? and thus producing hallucinations?
I have lots of documentation backing up by data.

Your cocaine example. Methamphetamine and other such stimulants can also too cause heart attacks. Remember the phrase speed kills? It is not the methamphetamine causing your heart attack or your cocaine, it is the release of norepinephrine (noradrenaline) and dopamine which causes these effects. So hey..its not structrure, its the function of that structure and there are many different structures with similar functions

(FYI: Cocaine acts as a potent dopamine reuptake inhibitor: its end result is increased dopamine, Meth mimics norepinephrine).

Please share with us your insightful documents on the 3,4,5-trimethoxy configuration and its ability to cause damage.

Keep away from personal attacks, they show your age.

Al/Hg Reduction!!!!

enima - 15-1-2005 at 18:04

haha finally!
Now back to the REAL thread.

The reduction of the nitrostryrene via Al/Hg.

(Health tip: Use gloves when working with the Al/Hg solution, the mercury can slowly make its way into your liver).

---
(From Rhodium Mirror)
#1: The original procedure by Hyperlab Bee #1.

Into a 3 liter kitchen jar.....yes, exactly :-).

So... into a 3 liter kitchen jar there’s placed:

- 75 mmoles of any nitrostyrene or phenylnitropropene (that should bee ~20 g) [Note 1]
- 200 mls GAA
- 300 mls IPA
- 100 mls water
- 0.75-1.3 g Hg(NO3)2 [Note 2]

Lastly, 40 g of kitchen Al foil is dumped into the soup.

The suspension is incubated for 30-40 mins after which it assumes black color and starts heating up.

At this moment SWIM simply takes the whole shebang and shakes it violently until the full dissolution of the nitro. At this point the mixture is usually vigorously boiling and is so hot that it can't bee held with bare hands.

From that moment the reaction proceeds for 5-10 mins, leaving a grey aluminous sludge as the result. The sludge is immediately dissolved in 300 g KOH in 800 mls water (which makes the mixture again boil so violently that the jar's bottom once fell off - after that we switched to using plastic canisters). Surprisingly, this treatment seems to not harm the product at all

The result is a two-phase mixture, the upper layer being the desired amine in IPA.

The procedure has been tested multiple times on the nitroalkenes corresponding to TMA-2, TMA-6 and 2C-H. It always gave yields not less than 70%. [Note 3]

[Note 1]: the nitroalkene must bee purified (rextallization from IPA) as much as possible. Using dirty nitroalkenes results in a sharp drop in yield.

[Note 2]: the actual quantity of mercuric salt was never accurately measured - SWIM just added it at the tip of the knife.

[Note 3]: The lowest yield thus far was 12 mls of 2C-H freebase from 20 g of 2,5-diMeO-nitrostyrene.
---

HgCl2 can be used instead of the nitrate, about 400mg would do the job.

I also recommend running the reaction until all the aluminum is consumed. Reflux it for an addition 2-3 hours, this will generally help with the yield and make the work up much easier. (The aluminum breaks down to Aluminum hydroxide).

Obviously you want to be using a round bottom flask with a condenser attached to avoid the reaction from going crazy. The Al/Hg type reductions are highly exothermic.

Blind Angel - 15-1-2005 at 18:50

If using Al powder instead of foil, should the amount be decreased because it's more reactive or all the foil is consumed in this reaction, thus 40g of Al powder be used too?

Darkfire - 15-1-2005 at 23:27

If the Al is in powder form, the reaction will be a mess. The temp would rise way too fast, the solvent would boil off way to fast. Ans the imine formation would likley not occur at the rate the Al is being used up.

Hum

VooDooMan - 16-1-2005 at 00:58

Quote:

Originally posted by Darkfire
If the Al is in powder form, the reaction will be a mess. The temp would rise way too fast, the solvent would boil off way to fast. Ans the imine formation would likley not occur at the rate the Al is being used up.

I never thought about that, a good point you brought up, I guess al foil was used for a specific reason, Does thickness and quality matter?

Exactly how much mercuric salt are we talking here, in that thread it stats only an estimate, to much of the catalyst couldnt be to good I dont think?

20 grams of the styrene or propane or either one can be used with the 20 gram it says?

Seems like an easy work up, even when using plastic jubs like they did!

thanx

HgCl2

VooDooMan - 16-1-2005 at 01:00

Quote:

Originally posted by enima
haha finally!
Now back to the REAL thread.

The reduction of the nitrostryrene via Al/Hg.

(Health tip: Use gloves when working with the Al/Hg solution, the mercury can slowly make its way into your liver).

---
(From Rhodium Mirror)
#1: The original procedure by Hyperlab Bee #1.

Into a 3 liter kitchen jar.....yes, exactly :-).

So... into a 3 liter kitchen jar there’s placed:

- 75 mmoles of any nitrostyrene or phenylnitropropene (that should bee ~20 g) [Note 1]
- 200 mls GAA
- 300 mls IPA
- 100 mls water
- 0.75-1.3 g Hg(NO3)2 [Note 2]

Lastly, 40 g of kitchen Al foil is dumped into the soup.

The suspension is incubated for 30-40 mins after which it assumes black color and starts heating up.

At this moment SWIM simply takes the whole shebang and shakes it violently until the full dissolution of the nitro. At this point the mixture is usually vigorously boiling and is so hot that it can't bee held with bare hands.

From that moment the reaction proceeds for 5-10 mins, leaving a grey aluminous sludge as the result. The sludge is immediately dissolved in 300 g KOH in 800 mls water (which makes the mixture again boil so violently that the jar's bottom once fell off - after that we switched to using plastic canisters). Surprisingly, this treatment seems to not harm the product at all

The result is a two-phase mixture, the upper layer being the desired amine in IPA.

The procedure has been tested multiple times on the nitroalkenes corresponding to TMA-2, TMA-6 and 2C-H. It always gave yields not less than 70%. [Note 3]

[Note 1]: the nitroalkene must bee purified (rextallization from IPA) as much as possible. Using dirty nitroalkenes results in a sharp drop in yield.

[Note 2]: the actual quantity of mercuric salt was never accurately measured - SWIM just added it at the tip of the knife.

[Note 3]: The lowest yield thus far was 12 mls of 2C-H freebase from 20 g of 2,5-diMeO-nitrostyrene.
---

HgCl2 can be used instead of the nitrate, about 400mg would do the job.

I also recommend running the reaction until all the aluminum is consumed. Reflux it for an addition 2-3 hours, this will generally help with the yield and make the work up much easier. (The aluminum breaks down to Aluminum hydroxide).

Obviously you want to be using a round bottom flask with a condenser attached to avoid the reaction from going crazy. The Al/Hg type reductions are highly exothermic.

Also what would the ratios look like if this was to be scaled up, not much but slightly, would every thing double correspondingly?
So roughly 400 mg HgCl2 for 20 gram styrene?

thanx

Upscaling

enima - 16-1-2005 at 10:45

Doubling works, although you probably won't need twice the amount of HgCl2. You could use about 600-700mg and that should work. (You could probably do with less solvent too).

Another interesting route would be a darzen condensation on the benzaldehyde, formation of the oxime with with hydroxylamine and finally reduction with magnesium/zinc and ammonium chloride/ potassium formate. You would be able to reduce more with this method. I'd recommend the magnesium over zinc as stirring the zinc with a magnetic stirrer can be troublesome. (lots of bumping). The disadvantages to this route are of course cost but you do end up with a product which is mercury free. (I'm sure there are trace amounts if not more present in products reduced by the Al/Hg method).

Oh before I forget.
On preparation of the foil, get the heavy duty stuff, put it thru a paper shredder, one of those which do square cutting, then get a coffee grinder and grind it up. (it will form little balls).

[Edited on 16-1-2005 by enima]

VooDooMan - 16-1-2005 at 11:12

Quote:

Originally posted by enima
Doubling works, although you probably won't need twice the amount of HgCl2. You could use about 600-700mg and that should work. (You could probably do with less solvent too).

Another interesting route would be a darzen condensation on the benzaldehyde, formation of the oxime with with hydroxylamine and finally reduction with magnesium/zinc and ammonium chloride/ potassium formate. You would be able to reduce more with this method. I'd recommend the magnesium over zinc as stirring the zinc with a magnetic stirrer can be troublesome. (lots of bumping). The disadvantages to this route are of course cost but you do end up with a product which is mercury free. (I'm sure there are trace amounts if not more present in products reduced by the Al/Hg method).

Oh before I forget.
On preparation of the foil, get the heavy duty stuff, put it thru a paper shredder, one of those which do square cutting, then get a coffee grinder and grind it up. (it will form little balls).

[Edited on 16-1-2005 by enima]

Good idea on the shredder - I was wonderfing can you give me a link on the above methods of reduction. All viable leads just personal prefreence on what to use how much to spend and yield!

thanx

Board Policy

UpNatom - 16-1-2005 at 13:13

Quote:

haha finally!
Now back to the REAL thread.

The reduction of the nitrostryrene via Al/Hg.

Actually the subject was synthesis of the nitrostyrene not reduction of it

.....

Quote:

The procedure has been tested multiple times on the nitroalkenes corresponding to TMA-2, TMA-6 and 2C-H. It always gave yields not less than 70%

...and this thread seems to have slipped almost unnoticed from the realms of the theoretical into the actual, practical discussion of the synthesis of a controlled drug.
Better yet it has developed into a discussion of potential refinements to the synthesis. (I'm asssuming everything after the snip marks in the post is your voice enima)

VooDooMan - 16-1-2005 at 13:41

Quote:

Originally posted by UpNatom

Quote:

haha finally!
Now back to the REAL thread.

The reduction of the nitrostryrene via Al/Hg.

Actually the subject was synthesis of the nitrostyrene not reduction of it

.....

Quote:

The procedure has been tested multiple times on the nitroalkenes corresponding to TMA-2, TMA-6 and 2C-H. It always gave yields not less than 70%

No one has said any thing about actually carrying out a complicated procedure like this, I bet most of us would be unable to acquire 345 trimethoxybenzaldehyde. not to mention all the other goodies, strictly theoretical on my part.

and as for the thread slipping, I would imagine all threads slip a bit, doesnt matter to much as long as its remotly linked IMHO!

thanx

enima - 16-1-2005 at 19:00

heh yes, access to the benzaldehyde is definitely not something many people have and those who do are not making mescaline.

But reductions are fun to do. There is always the vanillin route, but then you would have to have access to dimethyl sulfate or some other nasty methylating agent.

What would be fun though is getting 1,2-dihydroxybenzene, convert it the the benzaldehyde and make dopamine.

Blind Angel - 16-1-2005 at 20:46

is Dopamine or Serotonine active I.V. or parental or it can't travel throught the Blood Brain Barrier? Then poke a hole in my head, and insert me a permanent cateter, if that mean emotion control.

LeonardNimoy - 18-1-2005 at 13:33

Quote:

(I'm sure there are trace amounts if not more present in products reduced by the Al/Hg method)

This not the case. Correctly performed, the mercury salt is completely reduced to elemental mercury. The solvent and A/B extraction ensures that no mercury passes through to the final stage of the reaction. We are talking parts per billion here. You get more mercury from your fillings.

Most people can excrete mercury and a low level of intake is not cumulative (contrary to popular belief).

enima - 18-1-2005 at 14:17

Well I was speaking about the elemental mercury. Mainly it is a personal (paranoid) concern.

Also handling solvent post reaction is much safer with the zinc/magnesium method.

But yea mercury is still in _trace_ amounts. \

If need be a recrystallization / distillation can be performed to get a more pure product. (which you should be doing anyway if the final project is for 'lab rat' tests.)

LeonardNimoy - 18-1-2005 at 16:33

With good technique, mercury is mainly a desposal problem. Mercury waste should not be disposed of in normal refuse where it will end up in a landfill and polluting groundwater nor down the drain etc. Clearly label it as mercury contaminated waste and dispose of properly. Ask the council where to dispose of your cracked but unspilled mercury thermometer etc.

Mendeleev - 18-1-2005 at 17:00

I'm sorry I am sort of getting the thread off topic again, but I was just reading the huge Rosco vs. enima debate and I am still kind of muddled as to how harmful mescaline is. As for ecstacy, it is probably worse for your brain long-term than psychadelics. However what's up with mescaline? Is it something that I can do regularly? Simply put if I was to choose between regularly using shrooms and LSD vs. mescaline which once would be less harmful to me in the long run?

enima - 18-1-2005 at 18:24

I wouldn't recommend using mescaline weekly, or any psychedelic. People who use psychedelics on a regular basis (ie once a week)become "weird" and slighly disassociated from reality.

Also mescaline lasts 14-20 hours depending on the dose you take, with a 300mg dose, you will experience a 14 hour 'trip'. With a higher dose, say 600-650mg. You will have a full blown mescaline experience, expect it to last the 22 hours.

I am talking about time from injestion. On my debate with Rosco, my point was, it is the mechanism that mescaline worked in, (the same mechanism most psychedelics use) that caused disorders like hppd. The found that 5HT-2A receptors down-regulate when bound by mimics serotonin. When something binds a serotonin receptor, it causes it to fire in a pattern that is irregular from normal firing. Anyway, as a result of down regulation there are not many receptors aval. for serotonin to bind to and inhibit receptor firing (So the receptor fires in a manner which the brain does not have control over). People generally do not go insane. I think by insane Rosco meant schizophrenia/psychosis? But people can develope something called HPPD. HPPD is very far from insanity.

I recommend that when using mescaline you still to lower doses. Most people find them more pleasant. The duration will be less and chances of getting something like HPPD are reduced. At high doses of any psychedelic is it possible to schizophrenic type delusions. (Psilocin, LSD, 2CX, DOX, MDA, all will do this)

MDA can cause HPPD, and MDMA is slighly hallucinogenic, the more you use it, the higher doses you use it as, the more hallucinogenic it begins to become. (by no means do most consider it a psychedelic because hallucinations are generally subtle)
MDA does a very good job at inhibting the 5HT-2A receptors.

MDMA usage, on a regular basis will result in memory loss, attention deficit, social anxiety mainly because of the loss of serotonin axons. Axons do regrow, however this process can take years depending on dose.
It is possible to limit the brain damage of MDMA via dopamine reuptake inhbitors, and reutake inhibitors such as prozac/zoloft.

My Point: Mescaline will not make you go insane, however you may develope HPPD. MDMA is a reward experience but does come at the cost of brain damage.

If you opt to use the mescaline, do not it on a weekly basis, keep you doses on the lower end of the spectrum (this is true of all psychedelics). The reason I recommend this is because of the HPPD.

Annyway, becareful with drug use (A recent study came showing there is a correlation between marijuana and psychosis and marijuanas interaction with the dopamine system.)

enima - 18-1-2005 at 18:34

Another idea about mescaline synthesis.
(the goal to avoid methylating agents, making its synthesis easy and less hazardous).

1. p-anisaldehyde is dibrominted using a powerful halogenation mechanism. (One that is able to brominate nitrobenzene with a 95% yield). (the paper uses NBS, FeCl3, and acetonitrile as the solvent.) This is stirred at room temp.

2. Nucleaophillic substitution. Using sodium methoxide, you could replace the bromine with methoxy groups, this would leave you with a 3,4,5-trimethoxy configuration.

3. Hendry condensation, Reduction. (already been covered here).

I have the following questions concerning this. I know p-hydroxybenzaldehyde can be dibrominated using just bromine. My question is would powerful be capable of nitrobenzene methylation be capable of brominating both the 3,5 (which are favored by the methoxy and aldehyde groups). Even when dealing with two deactivating groups.

Attachment: Bromination of Deactived Aromatics.pdf (67kB)
This file has been downloaded 6663 times

Darkfire - 18-1-2005 at 18:44

There is no way in hell anyone would do mescaline weekly, mescaline itself wont alow it. Altho that might not make sence to the straightedged it does make sence to pysconaughts.

The axons of cells are never destroyed, thats ridiculas, sert's (seretonin reuptake terminals) simply move from the cell membrane and retract back into the cell or are inactivated by a protein, as habitual use of MD(M)A occurs, in order to adapt to the bodys draining seretonin reserves.

Mendeleev - 18-1-2005 at 19:07

I understand that weekly psychadelic use probably is bad, but what I gathered from Rosco's post was that it could make you schizophrenic. Either way would LSD be considered more gentle than mescaline?

enima - 18-1-2005 at 19:10

Darkfire, you have support for that because I have seen anything about that, serotonin axons according to many articles are destroyed. They are destroyed via radical oxidation. Axons do regenerate though.

3-methoxy-4-methylamphamine drains serotonin reserves and the brain does not "retract" its axons reuptake gates in this case. Same for other nontoxic serotonin releasers. Axonal damage can be seen via straning of the serotonin receptors. From the pictures I have seen the axon becomes much shorter. Also it doesn't make sense, if you are wanting to reduce the amount of serotonin you want those gates working, (prozac prevents the gates from working) so they can reuptake the serotonin that lies in the synaptic clef. The serotonin taken up is reused.

The damage caused by human consumption of MDMA maybe far less than that of the rats used for these studies. The doses given to rats are about 4-6mg/kilogram, that would make the avg for a 150lb male 272mg (2.7x human dose) to 409mg. (4x human dose)

The theory is not rediculous, what is though is a theory that MDMA causes programmed cell death.

---
Most people consider mescaline to be a very gentle psychedelic. Even psychedelic mushrooms bring on more intense (but shorter lasting of course) experiences.
Psychedelic phenethylamines are very gentle creatures. I have several friends that have used mescaline many times before and non of them are crazy.

[Edited on 19-1-2005 by enima]

Darkfire - 18-1-2005 at 21:17

Its not a toxic effect its nueroadaptation, the compound you are talking about may have a reduction of radical damage, but it will cause the same neuroadaption, as it is due to an exess of serotonin in the synapse and not caused by the drug itself.

Granted total axon damge has been show to occur after frequent heavy use, it has also been show that its not the MDMA that does it its some other chemical entering, most attribute this to dopamine.

[Edited on 19-1-2005 by Darkfire]

REf : 3-5- dimethoxy-4....dimethylamines

solo - 19-1-2005 at 18:50

I haven't read the whole thread so if this is a repeat ...sorry...solo

A new route to 3,5-dimethoxy-4-something-phenethylamines
by Labrat

Attachment: 345labrat.html (6kB)
This file has been downloaded 1578 times

Darkfire - 19-1-2005 at 22:43

Quote:

Originally posted by Blind Angel
is Dopamine or Serotonine active I.V. or parental or it can't travel throught the Blood Brain Barrier? Then poke a hole in my head, and insert me a permanent cateter, if that mean emotion control.

They cant be IVed becuase that will only bring them to the nerve cells themselves increasing their stockpiles if they are low, from depletion such as over use of MDMA. It wont release them into the synapse.

A few comments - other view of the situation

Ullmann - 21-1-2005 at 21:02

Enima :

I personally feel that mild so-called HPPD is sign of a healthy mind, consider yourself lucky if you are able to enjoy this on a regular basis. Usually it is more a chance than a disorder, as long as you can remain compatible enough to survive in the sick society. Why do you want to reduce HPPD? Not too intense it is a gift. Good and natural. The most probable after effect is an increase of wisdom, call it insanity. As you know insanity is a minority issue, altough when you become a part of this minority your conviction is that the masses are insane and a few alike ppl are sane.

Quote:

MDA can cause HPPD, and MDMA is slighly hallucinogenic, the more you use it, the higher doses you use it as, the more hallucinogenic it begins to become. (by no means do most consider it a psychedelic because hallucinations are generally subtle).

MDMA give more what I call "hallucinogenic" effects than psychedelics give (each used in normal dose). MDMA it is not what I would call psychedelic IMHO, it give practically no visionnary effect, altough it could bee called "hallucinogenic" at normal dosage. Well Of course it is still only slightly hallucinogenic, its not BZ or datura ;-). Psychedelics are visionnary materials, "hallucinogen" is misleading here. This rambling is just a vocabulary issue, it doesnt really matter.

Quote:

My Point: Mescaline will not make you go insane, however you may develope HPPD. MDMA is a reward experience but does come at the cost of brain damage.

If you opt to use the mescaline, do not it on a weekly basis, keep you doses on the lower end of the spectrum (this is true of all psychedelics). The reason I recommend this is because of the HPPD.

M would generally be much more rewarding that MDMA IMHO. It depends of the issues the labrat would want to adress of course. Taking a good medium dose of M (400 mg of the sulfate for instance) should not be a problem if you are in a good set/setting. Dont be afraid of the so called HPPD but use the good compound with respect and dont be a moron.

Quote:

Annyway, becareful with drug use (A recent study came showing there is a correlation between marijuana and psychosis and marijuanas interaction with the dopamine system.)

Personally I consider marijuana a much more difficult substance to dealt with than say M or other usual PEAs. It is a very dark, strong and negative compound cannabis. Not very insightfull neither, but alot of paranoid issues. It is habituating too. I would definitely skip on that one. ;-)

Professor Mendeleev :

Variation of the toxics is the key : be sure to eat more or less regularly each of them tryptamines, PEAs and ergolines by rotating their use aiming for the maximization of spectrum of insightfull effects. I agree with Darkfire on the regular M issue. It is a profound experience, better decant it with other compounds inbetween sessions ;-)

Rosco :

Personally I think you are completely misleading. I cannot agree with you on any point. Btw good luck with your future trial of the Rage Compound, you will enjoy that happy experience I am sure ;-)

I really hate the way Science take the charm away, especially in this utterly unmaterialistic, unfactuable and hard to monitor issue of the human mind. Science as nothing to do here. Eat and learn from yourself through direct experience. Threads like this one is loss of time, better study art of o’chem instead as Traugott pointed out.

[Edited on 22-1-2005 by Ullmann]

Darkfire - 22-1-2005 at 01:14

I love your post. People wanna label anything as disorders no days. HPPD is what goverment calls blinding flashes of insight. "HPPD" brought me to my knees several times. I was nearly in tears two memorable times within the first week or so after my mescaline trip. At the pound i saw those dogs, and my hart was just breaking, and i saw this small new plant just stating to grow through this crack of dirt all alone on the way home from school. Some times it bored on pysocosis and cuase extreme depression. Then i realised that it was just what other thought of it i felt that way. since then i treat mescaline like its a god to me. It took me from the average type of person, and forged this new version of me, more powerful and just and faithful, who i am now is light years above who i was. The self esteem and self belife i poses now is beyond words, it was a long hard road out of the hell mescaline forced me in, but its worth it. http://www.angelfire.com/theforce/highexplosives/DarkfiresSh... I wrote that soon after, its a nice long trip report.

some thoughts on the issue

Vitus_Verdegast - 23-1-2005 at 06:52

Quote:

The damage caused by human consumption of MDMA maybe far less than that of the rats used for these studies. The doses given to rats are about 4-6mg/kilogram, that would make the avg for a 150lb male 272mg (2.7x human dose) to 409mg. (4x human dose)

Have you seen what many of those pill poppers on trance parties ingest on a single evening? Some of them do this every weekend, and many do not care at all about increased neurotoxicity caused by combining MDMA with other stimulants as amphetamine or cocaine. And we are not even mentioning the additional effects of excessive alcohol consumption. I'd say the damage could be even worse but we'll have to see about that in 10 or 20 years from now..

Give me one normal dose of a safe psychedelic with its HPPD package any day of the week.

Of course if everyone would do it the Shulgin way things would be different, but IMO it is more likely that hell will freeze over first.

About 3-MeO-4-Me-amphetamine, I'd be very careful with that one. From PiHKaL:
http://www.drugsinfo.net/pihkal/pihkal123.html

Quote:

Some years ago a report appeared in the forensic literature of Italy, of the seizure of a small semitransparent capsule containing 141 milligrams of a white powder that was stated to be a new hallucinogenic drug. This was shown to contain an analogue of DOM, 3-methoxy-4-methylamphetamine, or MMA. The Italian authorities made no mention of the net weight contained in each dosage unit, but it has been found that the active level of MMA in man is in the area of 40-60 milligrams. The compound can apparently be quite dysphoric, and long lived.

I can't access Rhodium's mirror site now, but there is mentioned 3-hydroxy-4-methylamphetamine, which can be assumed to be one of the primary metabolites of MMA, and the pharmacological profile didn't really look healthy at all.

Remember when 4-methylthioamphetamine was being promoted and sold as a safe legal non-neurotoxic MDMA-like compound? Caveat emptor!

Quantum - 23-1-2005 at 09:11

Mescaline is used as a standard to scientificly rate other drugs of the same sort - nothing more nothing less.

I don't undestand all this about 16 hour trips - erowid states the trip lasts more like 8hours. Perhaps your body is differnet from most.

All this talk of journals is counterproductive. Journals can be wrong as is the many cases of misleading tests on other drugs throughout the years.

Anyway if one is to look at Lab Tips(yes I know its totse) they will see a great post detailing the synth of benzaldehyde(and more) using very common OTC chems and toluene.

As far as mescaline goes I think its up there with shrooms and LSD25 in terms of safety. Erowid says know your body and mind and that should be done. Anyone reading the trip reports would agree that the benefits outweight the risks for these drugs - used correctly they are very good

Darkfire - 23-1-2005 at 10:52

Erowids a good source, but its got its mistakes. 8 hours is bullshit.

Quantum - 23-1-2005 at 11:04

I think that for you it lasted more. For most people it lasts 8 hours.

Face it - you fucked your trip up:
No sitter
Unknown dose
Parents were home - your were inside at night

Better would be with friends, outside in the day time with a known dose of extract not juice

Poor thinking leads to poor planning leads to a bad trip

Darkfire - 23-1-2005 at 11:14

My trip wasnt bad, and i knew what i was doing and getting into and i had things that needed resolution between me and my parents. Tripping is suposed to be done alone in silent darkness in high doses. Thats what pyscidelics really are, not thing to have fun with friends. Tripping isnt suposed to be fun. Ive talked to at least 4 other people who have done a varity of doses from a normal light dose up to 1 gram of mescaline. Trips ranged from 12 to 48 hours. Never 8.

guaguanco - 26-1-2005 at 09:14

Quote:

Originally posted by Darkfire
Tripping isnt suposed to be fun.

Shulgin would certainly disagree with you. So do I.

Darkfire - 26-1-2005 at 15:20

If its fun in the truest sence of the world i guess your corect. Its not fun like getting drunk is. It much more than that.

A touch of terror gives the stamp of validity to an experience because it means, "This is real." We are in the balance. We read the literature, we know the maximum doses, the LD-50 and so on. But nevertheless, so great is one's faith in the mind that when one is out in it one comes to feel that the rules of pharmacology do not really apply and that control of existence on that plane is really a matter of focus of will and good luck.

I'm not saying that there is something intrinsically good about terror. I'm saying that, granted the situation, if one is not terrified then one must be somewhat out of the full dynamics of what is happening. To not be terrified means that one is either a fool or that one has not taken a compound that paralyses the ability to be terrified. I have nothing against hedonism, and I certainly live my life in that philosophy. But the experience must move one's heart, and it will not move the heart unless it deals with issues of life and death. If it deals with life and death then it will move one to fear, it will move one to tears, it will move one to laughter.

guaguanco - 27-1-2005 at 15:28

Well, it certainly can be an exciting and scary experience. But (done properly) it's more fun than a barrel of monkeys. So I guess we're more or less in agreement.

Darkfire - 27-1-2005 at 16:15

Fun is one adjective to describe it, but labled strictly as somethign to do for fun cuase your bored, is nothing short of insane.

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