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Author: Subject: 3,4,5-trimethoxy-beta-nitrostyrene synthesis
Rosco Bodine
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[*] posted on 13-1-2005 at 19:18


Here's a thought . Are prions toxic ?
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[*] posted on 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




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Rosco Bodine
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[*] posted on 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 .
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[*] posted on 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.



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[*] posted on 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.
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[*] posted on 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.



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Rosco Bodine
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[*] posted on 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 .
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[*] posted on 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).
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[*] posted on 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.



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[*] posted on 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.




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[*] posted on 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.
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Rosco Bodine
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[*] posted on 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 .
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Rosco Bodine
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[*] posted on 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 .:P
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[*] posted on 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]




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Rosco Bodine
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[*] posted on 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 .
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[*] posted on 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.
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[*] posted on 15-1-2005 at 18:04
Al/Hg Reduction!!!!


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.
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[*] posted on 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?



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Darkfire
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[*] posted on 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.



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[*] posted on 16-1-2005 at 00:58
Hum


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
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[*] posted on 16-1-2005 at 01:00
HgCl2


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
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[*] posted on 16-1-2005 at 10:45
Upscaling


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]
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[*] posted on 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
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[*] posted on 16-1-2005 at 13:13
Board Policy


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)
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[*] posted on 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%


...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)


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
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