PhenethylamineMachine
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Route specific impurities piperine/piperonal
piperonal prepared via a catalytic ruthenium tetroxide oxidation of piperine extracted from black pepper is becoming a common precursor in the
synthesis of 3,4-methylenedioxyphenyl-2-nitropropene and 3,4-methylenedioxyphenyl-2-propanone. However, recent discoveries have demonstrated that
during the oxidation process 6-chloropiperonal was produced. The means by which this occurs are not understood and have yet to be elucidated.
When the 3,4-methylenedioxyphenyl-2-nitropropene and 3,4-methylenedioxyphenyl-2-propanone that were produced from piperine derived from black pepper
are used in the synthesis of 3,4-methylenedioxy-N-methyl-amphetamine a chlorinated analogue compound is also produced,
2-chloro-4,5-methylenedioxymethamphetamine (6-Cl-MDMA), and is present in the final product.
I can find very little information regarding 6-chloro-MDMA or it's pharmacological properties or toxicity, and have been seeking any available
information on the topic.
Mainly, I wanted to speculate and attempt to understand how exactly this 6-chloropiperonal was generated in the first place.
also, to discuss potential implications and effects of this compound being present in chemical samples which are being consumed by humans.
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Bert
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Mood: " I think we are all going to die. I think that love is an illusion. We are flawed, my darling".
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also, to discuss potential implications and effects of this compound being present in chemical samples which are being consumed by human
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Only part I am qualified to comment on.
Implications: Large drug companies occasionally fuck the dog. They have QC departments and nervous lawyers chasing the mistakes, miscalculations and
unintended consequences.
Individuals making chemicals for their own consumption will likely do the best they can to not make a bad product, for obvious reasons. It is the
individual chemists PERSONAL issue if they are ignorant of a potential hazard they create. Ethically, this is not a problem for me, if they don't
expose unknowing others to their work and the potential consequences. No distributing to anyone less knowledgable than, say, your lab partner. I know.
Snowball's chance in hell you all will let a batch go no further than that, but ethically, that is where it SHOULD stop
Stuff made to be sold? By people who don't put their name and address on the package, and are wanting the largest profit? Distributed via multilevel
black markets, with no producer accountability?
Large chance for ignorant and trusting people to consume shoddy, potentialy dangerous chemicals, near zero chance those harming them will be held
accountable.
One of many reasons to make your own or do without.
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Texium
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Thread Moved
24-3-2018 at 08:39 |
PhenethylamineMachine
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Quote: Originally posted by Bert  |
| Quote: |
also, to discuss potential implications and effects of this compound being present in chemical samples which are being consumed by human
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Only part I am qualified to comment on.
Implications: Large drug companies occasionally fuck the dog. They have QC departments and nervous lawyers chasing the mistakes, miscalculations and
unintended consequences.
Individuals making chemicals for their own consumption will likely do the best they can to not make a bad product, for obvious reasons. It is the
individual chemists PERSONAL issue if they are ignorant of a potential hazard they create. Ethically, this is not a problem for me, if they don't
expose unknowing others to their work and the potential consequences. No distributing to anyone less knowledgable than, say, your lab partner. I know.
Snowball's chance in hell you all will let a batch go no further than that, but ethically, that is where it SHOULD stop
Stuff made to be sold? By people who don't put their name and address on the package, and are wanting the largest profit? Distributed via multilevel
black markets, with no producer accountability?
Large chance for ignorant and trusting people to consume shoddy, potentialy dangerous chemicals, near zero chance those harming them will be held
accountable.
One of many reasons to make your own or do without.
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I understand what you are saying, though I don't want you to misunderstand my intentions. I have no interest in the marketing of any chemicals, my
concerns are centered around research and potential harm reduction.
Here, I found this research article on the topic:
| Quote: | Abstract
This work examines the chemical synthesis of 3,4-methylenedioxy-N-methylamphetamine (MDMA) from piperonal prepared via a catalytic ruthenium tetroxide
oxidation of piperine extracted from black pepper. A variety of oxidation conditions were experimented with including different solvent systems and
co-oxidants. A sample of prepared piperonal was successfully converted into MDMA via 3,4-methylenedioxyphenyl-2-nitropropene (MDP2NP) and
3,4-methylenedioxyphenyl-2-propanone (MDP2P) and the impurities within each product characterised by GC–MS to give a contaminant profile of the
synthetic pathway. Interestingly, it was discovered that a chlorinated analogue of piperonal (6-chloropiperonal) was created during the oxidation
process by an as yet unknown mechanism. This impurity reacted alongside piperonal to give chlorinated analogues of each precursor, ultimately yielding
2-chloro-4,5-methylenedioxymethamphetamine (6-Cl-MDMA) as an impurity within the MDMA sample. The methodology developed is a simple way to synthesise
a substantial amount of precursor material with easy to obtain reagents. The results also show that chlorinated MDMA analogues, previously thought to
be deliberately included adulterants, may in fact be route specific impurities with potential application in determining the origin and synthesis
method of seized illicit drugs.
https://www.researchgate.net/publication/293330219_The_synth...
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So, we know the route specific impurity 6-chloro-piperonal is formed during the oxidation of piperine, yet we do not know how or why this is
happening.
| Quote: | | Interestingly, it was discovered that a chlorinated analogue of piperonal (6-chloropiperonal) was created during the oxidation process by an as yet
unknown |
Further more, it is probable that a good amount of 6-chloro-MDMA is going to be unintentionally consumed by those obtaining certain phenethylamines on
the black market.
Information on the compound is sparse, and for once Wikipedia displays most of what is known:
| Quote: | | 6-Chloro-MDMA (6-Cl-MDMA, 2-Cl-4,5-MDMA) is a derivative of the amphetamine drug MDMA, which has been identified both in seized "Ecstasy" tablets and
in urine samples from drug users.[1][2] It is thought most likely to be an impurity from synthesis and its pharmacological properties have not been
established, however it has been banned in several countries. -Wikipedia |
Though Wikipedia obviously has not updated since these articles were published, as it is pretty clear the compound is a route specific impurity.
I have also been researching methods for removing this impurity, but in all honesty I am more interested in the means by which it is being formed in
the first place...
I understand that as far as organic chemistry goes, these topics are pretty well in a gray area, and that it is fully reasonable to expect some
reluctance in discussing them, however, I figured if I stuck purely to research and did not stray into any subjects which pass beyond that gray area,
that there would not be any issues.
The communities which are generally concerned with these subjects aren't advanced enough to answer my inquiries, and I don't want to ask these
questions in my academic circle for obvious reasons. I figured there were some top-notch organic chemists lurking around here...
...thank you for the response though, it is appreciated.
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JJay
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I assume you're looking at this:
Attachment: j.scijus.2016.01.003.pdf (511kB)
This file has been downloaded 1231 times
I'm certainly not claiming to be a top-notch organic chemist (there are some on this board), but as far as hobbyists go, I don't think I'm a slouch
either.
The only obvious source of chlorine is the RuCl3 used in situ to produce ruthenium tetroxide. A strong oxidizer with chlorides can pretty easily
produce dichlorine or chlorine radicals. The chlorination probably happens before oxidation to piperonal since piperonal would be hard to chlorinate
directly at that position.
[Edited on 28-3-2018 by JJay]
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Reboot
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Mm, I'd say the chlorine came from the formation of the catalyst (from ruthenium chloride.) The reaction mechanism by which it was incorporated into
the product is beyond my modest skills. :-)
Halogenated phenethylamines have a long history of being psychoactive, however there's no reason to think it might have an exceptional levels of
activity. Given the modest trace amounts that appear to be present in the chromatograph spectrum, I would feel confident in saying that the presence
of the chloro-MDMA analog is of no pharmacological significance to users.
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PhenethylamineMachine
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| Quote: Originally posted by JJay | I assume you're looking at this:
I'm certainly not claiming to be a top-notch organic chemist (there are some on this board), but as far as hobbyists go, I don't think I'm a slouch
either.
The only obvious source of chlorine is the RuCl3 used in situ to produce ruthenium tetroxide. A strong oxidizer with chlorides can pretty easily
produce dichlorine or chlorine radicals. The chlorination probably happens before oxidation to piperonal since piperonal would be hard to chlorinate
directly at that position.
[Edited on 28-3-2018 by JJay] |
Pdf download did not work, crashed my device. I am trying to respond but am having technological issues at the moment.
Ill try again on another device.
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PhenethylamineMachine
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| Quote: Originally posted by Reboot | Mm, I'd say the chlorine came from the formation of the catalyst (from ruthenium chloride.) The reaction mechanism by which it was incorporated into
the product is beyond my modest skills. :-)
Halogenated phenethylamines have a long history of being psychoactive, however there's no reason to think it might have an exceptional levels of
activity. Given the modest trace amounts that appear to be present in the chromatograph spectrum, I would feel confident in saying that the presence
of the chloro-MDMA analog is of no pharmacological significance to users. |
Thank you for the response, very informative.
I had a long response relating to piperine oxidation typed out and my device crashed on me...Ill have to go into detail on another device, it's
frustrating when you write a good deal of technical information complete with links and citations and then your device crashes...
On another note, when it comes to halogenated phenethylamines I condenser myself quite knowledgeable. That magic 4 position is fascinating, though
it's not just halogens, alkyl chains on 4 also produce some pretty fascinating molecules. One molecule, 2,5-dimethoxy-4-methyl-phenethylamine has been
of particular interest to me. At lower doses this molecule appears to have significant nootropic properties. I am straying off topic though...
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JJay
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Huh, weird. Don't worry, I'm not trying to hack you or anything, LoL. But it sounds like you might have some bad software running on your machine.
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PhenethylamineMachine
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| Quote: Originally posted by JJay |
Huh, weird. Don't worry, I'm not trying to hack you or anything, LoL. But it sounds like you might have some bad software running on your machine.
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Oh, No, I am not worried about that, besides, this device has already been hacked, so there isn't anything useful or valuable on it, I only mentioned
my malware issues because often they cause my device to crash, or prevent me from opening up links, things of this nature, so there are no worries on
my part, just a good deal of technical issues which interfere with my posting.
Anyway, I think I had a big post relating to heating protocatechualdehyde with potash and methylene iodide, or decarboxylating oxidation of
3,4-methylenedioxy mandelic acid by nitric acid in aqueous medium in the presence of hydrochloric acid...or something along those lines.
...any way, it's all lost now.
ruthenium chloride...?
In the research posted piperonal was prepared by a catalytic ruthenium tetroxide (RuO4) of piperine...
Any way, it's been a while, though if this topic still holds any relevance I am still willing to discuss it.
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PhenethylamineMachine
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I was not sure if I should put this next piece here or give it it's own thread. in all honesty it probably deserves it's own thread, but I figured
that it was close enough on topic that I could put it here without bothering everybody with a new thread on the matter.
I found an article which mentions an intermediate in the synthesis of valuable pharmaceutical compounds relating to piperonal* namely
5-trifluoromethyl-piperonal which can be used to produce 6-amino-piperonal as well as other valuable substituted piperonal compounds. The work
describes a palladium-catalyzed synthesis method of 5-trifluoromethyl-piperonal starting from 5-iodo-piperonal, I can easily understand the chemistry
even with the poor translation, its the other information regarding this research that the translation makes difficult.
* | Quote: | | 6-amino piperonal is an important pharmaceutical intermediates in the antimalarial drugs, anti-Alzheimer's drugs, antihypertensive and antipsychotic
drugs have applications; sedative, anticonvulsant and antidepressant effects of piperine may synthesis of piperonal. Therefore, synthetic pepper
aldehyde derivative has been of concern. |
Fascinating material, but a poor translation.
I have been trying to find better translations without success, but again, I am on a an old device which is full of malware and barley functions as it
is...
Here is what I mean:
| Quote: | FIELD
[0001] The present invention relates to a pharmaceutical intermediates art of organic synthesis, particularly, the present invention relates to a
pharmaceutical intermediate
The method of synthesis of 5-trifluoromethyl-piperonal.
Background technique
[0002] piperonal derivative is an important organic intermediates, have extensive use in the field of fine chemicals perfumes, fragrances, pesticides,
pharmaceuticals, etc., they provide an important part of the development of new compounds with biological activity. Such as:
6-amino piperonal is an important pharmaceutical intermediates in the antimalarial drugs, anti-Alzheimer's drugs, antihypertensive and antipsychotic
drugs have applications; sedative, anticonvulsant and antidepressant effects of piperine may synthesis of piperonal. Therefore, synthetic pepper
aldehyde derivative has been of concern.
[0003] piperonal derivative at the 5 position with a leaving group having good functionality value, the present invention contemplates a new
derivative of piperonal: 5_ trifluoromethyl piperonal, since the 5-position trifluoromethyl having a relatively strong activity, the compound can be
used as intermediates for the preparation of a derivative of any of piperonal containing. Trifluoromethyl having a high electronegativity, high
stability, high permeability and other special features fat-soluble, which is incorporated piperonal can substantially increase the polarity,
lipophilicity and stability, significantly enhance biological activity. Trifluoromethyl piperonal with less dosage, low toxicity, high efficacy, high
metabolic capacity and other characteristics, it has very important applications in the field of biochemistry, medicine, pesticides, dyes, and the
like and functional materials.
https://patents.google.com/patent/CN103242284A/en
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Cool stuff right? But it's not as easy to ingest with the poorly translated text, I find that in some cases I will have to read the poor translation
several times over before properly understanding the intended communication.
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Reboot
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Generated in situ from ruthenium chloride. Re-read their 'methods' section.
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PhenethylamineMachine
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What ruthenium chloride?
The piperonal was prepared through a catalytic ruthenium tetroxide (RuO4) of piperine...
Methods section? We might not be speaking about the same research article...
I apologize for any potential difficulty, but something is not properly connecting for me, and I really want to understand this, I would appreciate
any help with clarification.
Much thanks.
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Reboot
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| Quote: Originally posted by PhenethylamineMachine | What ruthenium chloride?
The piperonal was prepared through a catalytic ruthenium tetroxide (RuO4) of piperine...
Methods section? We might not be speaking about the same research article.. |
The paper you cited in your second post (Plummer et al) is littered with references to ruthenium chloride. It's in the materials and methods
sections, it's in the reaction diagrams. See "Figure 1" for where it gets turned into the oxide in situ.
https://www.researchgate.net/publication/293330219_The_synth...
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JJay
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I suspect that if the RuO4 were prepared from RuO2, there would be no chlorinated piperonal in the product.
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zed
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Probably it is wishful thinking, but it has crossed my mind that it is remotely "possible" that Heliotropin might be derived from Piperic acid,
without oxidation.
Benzaldehyde can be recovered from Cinnamaldehyde, via steam distillation from a basic solution. A reverse Aldol...or, Re-hydration. About a 70%
yield, as I recall. There is a reference to the process on Wiki. https://en.wikipedia.org/wiki/Benzaldehyde
C6H5-CH=O + CH3CH=O <-> C6H5-CH=CH2-CH=O +H2O
C6H5-CH=CH2-CH=O +H2O +NaOH +Steam > Benzaldehyde + Acetaldehyde Gas.
Piperic acid is produced by the condensation reaction of 3,4-Methylenedioxy-cinnamaldehyde, with Acetic Anhydride. An Aldol type reaction. Is this
also a reversible reaction?
If both sequences of reactions are reversible, then it might be possible to just steam distill Heliotropin from a basified solution of piperic acid.
Leaving behind the Sodium Salt of Acetic Acid, While distilling out Heliotropine, and Acetaldehyde Gas.
Might not be a huge yield, and the process might not be commercially viable. But, Heliotropin is hard to come by, these days. Worth a try.
[Edited on 18-4-2018 by zed]
[Edited on 18-4-2018 by zed]
[Edited on 18-4-2018 by zed]
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