Author Topic: Thiophene analog of mephedrone  (Read 234 times)

mildronate

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Thiophene analog of mephedrone
« on: May 13, 2012, 06:37:09 PM »
Just idea about synthesing thiophene analog of mephedrone. Anbody know something about it? I know that Chinise make Methiopropamine, howabout thiophene analog of pyrovalerone?

Tsathoggua

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Re: Thiophene analog of mephedrone
« Reply #1 on: May 13, 2012, 07:04:56 PM »
REALLY fucking bad idea. Toady wouldn't touch mephedrone or methedrone with a ten foot, dog shit covered dengue virus-contaminated stick. The main metabolites are the corresponding ephedrines, and are very, very potent vasoconstrictors. Dangerously so.

Methiopropamine has been noted, as have other thiophene analogs of amphetamines, to be much more vasoconstrictive than the parent amphetamine. So One can expect, extrapolating from the SAR of amphetamines, cathinones and the analogs with the thiophene ring in place of phenyl, that the thiophene homolog of mephedone, or of methedrone, to be both highly vasoconstrictive itself, and to produce large quantities (especially given that mephedrone/methedrone are widely noted all over the net, to lend themselves to extremely compulsive, very reinforcing, addictive patterns of use, blowing multiple grams in a session)

The MPA analog of mephedrone and/or methedrone is asking for serious, dangerous levels of vasoconstriction, and quite possibly, loss of extremities or even deaths. Not to mention serious strain on the cardiovascular system.

Avoid these like the plague!
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dream0n

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Re: Thiophene analog of mephedrone
« Reply #2 on: May 13, 2012, 08:56:16 PM »
Conclusion, it would be very irresponsible to synthesize those compounds.
off to bigger and better things - don't worry I will visit from time to time

Tsathoggua

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Re: Thiophene analog of mephedrone
« Reply #3 on: May 13, 2012, 09:03:42 PM »
Yes. These WILL be toxic, full of side effects, as well as extremely compulsively addictive and reinforcing. IIRC, thiophene substitution in place of phenyl in amphetamines tends to lower potency by weight also. Thus tending towards still greater production of the toxic, vasoconstrictive ephedrine analog.

If synthed, and tasted, chances are very probable indeed that the resultant compounds would be damn addictive, and after a while, and after the user has snorted, bombed, plugged etc. a metric arseload of said compounds, then will come SEVERE vasospasm and probable neurotoxicity.

Mephedrone and methedrone were bad enough ideas and should never have been released onto the RC market. Seriously...what the bloody christ were they thinking. Para-methyl, and para-methoxyamphetamine are notorious for being seriously neurotoxic and extremely dangerous drugs, the beta-keto derivatives need never have seen the light of day. And there is no reason to think that the benzothiophene analogs should be made either.
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Enkidu

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Re: Thiophene analog of mephedrone
« Reply #4 on: May 14, 2012, 04:23:26 AM »
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These WILL be toxic, full of side effects, as well as extremely compulsively addictive and reinforcing
If the substitution is even active.. According to DOI: 10.1021/jm9017465, the thiophene analog of bupropion is inactive at DAT, NET, and SERT. Please back up your statements with fact.

mildronate

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Re: Thiophene analog of mephedrone
« Reply #5 on: May 14, 2012, 06:13:06 AM »
How about other heterocycles, furan?

Tsathoggua

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Re: Thiophene analog of mephedrone
« Reply #6 on: May 14, 2012, 10:02:14 AM »
Toady would simply avoid ALL amphetamines or cathinones with a mono-substitution at the 4-position. They are all nasty, from everything he has ever heard about any of them.

Para-haloamphetamines are outright neurotoxins, powerful, selective, serotonergic neurotoxins, used in research on animals to selectively ablate 5HTergic neurons. With the exclusion of para-fluoroamphetamine, which produces a short lived 5HT depletion, but nothing too dramatic, and not the long-lasting damage caused by para chloro, bromo and iodoamphetamine.

Pseudohalogens such as cyano, should be avoided, don't know if they fry serotonergic axons, but it isn't worth finding out.

4-methylamphetamine is known, appeared in russia, and produced long lasting, serious personality changes, insomnia, and other severe effects.

4-methoxyamphetamine, aka PMA is a potent 5HT releaser, like MDxx, but also with an EXTREMELY steep dose-response curve, nicknamed flatliners, for appearing as a substitute for MDxx in pills, causes severe temperature elevation due to, IIRC, MAOI(a) effects, neurotoxic, it appears from time to time in Es, and when it does, deaths typically occur. The precursor essential oil is much easier to obtain, and far less watched than is the sassafrass oil needed as a MD(M)A precursor.

5-methylthioamphetamine is apparently not neurotoxic, but it IS a MAOI(a) and as such, being also a 5HT releaser etc. is still dangerous, and poses the risk of serotonin syndrome. Which I can tell you, is a horrendous, slow, painful way to die. Toady's stalker/soulmate went through it once, due to a sudden, unpredictable interaction between fluvoxamine and a triptan migraine med. She thought she was going to die that night, and couldn't move to summon help.

Methedrone, and mephedrone are known to be powerful vasoconstrictors, and known metabolites include the toxic, vasoconstrictive ephedrine derivatives.

If you take toady's advice, simply avoid all para-monosubstituted amphetamines, alkylamphetamines, cathinones and cathinone derivatives. Avoid like the plague. Nothing good is going to come from this, only a waste of precursors.

The 2,5-disubstituted-4X-amphetamines/cathinones are another matter entirely.Bring 'em on :D

The cathinone analogs of known nasties have been released, even, by some dumb fucking profiteering cocksuckers, para-bromethcathinone. Wouldn't touch that with a 20-foot pole covered in diarrhea from a cholera-infected muslim HIV patient. Unless maybe to ram a few grams up the vendors fucking arse ring(s)

Don't waste your lab time, your energy and thought synthesizing these compounds, save for in-vitro research, analytical chemistry. Toxic, nasty bunch,they are, both the (para-methyl, methoxy, methylthio phenethylamines, the amphetamines, cathinones and methcathinones. Primary amine cathinones are so unstable they like nothing better than to dimerize during workup to give rubbish, primary amine beta-keto derivatives are unstable, and MUST be produced instead of the bare amine, as prodrugs using a pthalimidopropiophenone as precursor, the body chews off that pthalimide, and releases the active, primary amine cathinone suitably diluted in body fluid.


Good point, enki. Assuming activity for novel derivatives. Toady was referring however to known, neurotoxic, vasoconstrictive toxic rubbish, rather than new compounds entirely. Although its highly likely that toxic products will result. Simple para-substituted cathinones and M-cats seem overall to be pretty damn noxious with the potential both for severe toxic reactions, and for ending up as nasty ass ephedrine metabolites with extremely potent,vasoconstrictive ephedrine derivatives.                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                   
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I'm hyperbolic, hypergolic, viral, chiral. So motherfucking twisted my laevo is on the right side.

fresh1

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Re: Thiophene analog of mephedrone
« Reply #7 on: May 14, 2012, 10:34:31 AM »
 
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Toady's stalker/soulmate went through it once,

lmao I dont think I have ever seen these two words in the same sentence, let alone beside each other :o

good stuff everyone... I agree this shit doesnt need help to be produced

don't take this as a dis mildronate just some wasps are quite responsible  ::)

keep up the ideas  8)
"Curiosity is a gift"

mildronate

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Re: Thiophene analog of mephedrone
« Reply #8 on: May 14, 2012, 03:53:09 PM »
i know that phtalimide, very interesting, there was one israel company producing with trade name SUB COCA. I need good legal stimulant which is not structure analog and little known.

mildronate

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Re: Thiophene analog of mephedrone
« Reply #9 on: May 14, 2012, 07:07:25 PM »
But i am speaking about phenyl ring change with thiophen not thiophen substition at benzene ring para place. I speaking about 1-(thiophen-2-yl)-2-methylaminopropane. I am not interested in ring substition (I am interested to change phenyl with something else) and there napthalene ring also is not very good in nowdays, i need 100% legal coumpound.

Tsathoggua

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Re: Thiophene analog of mephedrone
« Reply #10 on: May 14, 2012, 08:00:59 PM »
Those thiophene mephedrone analogs would actually be MORE dangerous than mephedrone itself. Which was highly toxic to begin with. MPA (methiopropamines trade name) was a thiophene analog of methamphetamine (or it might have been amphetamine, memory fails toady...besides he's JUST woken up to do his morning shot of oxy literally this minute...and of course, had to check for new posts at the vespiary:D and another forum for hobbyist biochemistry, as well as pharmacology and drugs) and it was quite a powerful vasoconstrictor in comparison with(meth)amphetamine, the presence of the thiophene ring as the aryl group tends to make amphetamines more powerful vasoconstrictors. Its true, cathinones don't always match up, SAR-wise to their descarbonyl counterparts, but in the case of an analog derived from a notorious, well known as toxic derivative of the truly noxious and often lethal PMA, that will probably lend it additional potency to the vasoconstrictive properties. Presumably making it a more potent agonist at alpha1 adrenoreceptors. And of course, there will be the corresponding ephedrine analog being produced as a metabolite, which may be all that, and a (nor)adrenergic release agent also.

Not good, There is nothing good that can come of this, and very little promise in simple para-ring substituted amphetamines or cathinones (which are of course, just beta C=O amphetamines)

What would interest toady, is seeing protected prodrugs of the psychedelic phenethylamines and amphetamines. A secondary amine is known to abolish most psychedelic effects and turn them into relatively little known, rather odd sounding compounds such as ARIADNE and BEATRICE, so pthalimidoacetophenones, and pthalimidopropiophenones could make way for exploration of basically enough compounds to double Shulgin's work in PIHKAL.

The Gabriel synthesis would work just fine for these, simply omitting the hydrazinolysis step usually performed to remove the pthalimide.

As for stimulants, what about the selective DARI hxxp://en.wikipedia.org/wiki/GYKI-52895
This is a 2,3-benzodiazepine, and highly selective DARI. Beware, however, if aiming towards producing analogs, as many 2,3-benzodiazepines are antagonists of the AMPA type ionotropic glutamate receptor which is important for fast excitatory signaling, and long term potentiation, especially in the hippocampus, where it is critical for learning and memory.
 

This is a benzodiazepine, although not of the same type that gives us the clinically used sedatives, which are in any case, in SCH-IV or V IIRC, so could not be judged analogs in a court case, as to be an analog, the drug must be in schedule I or II.
Nomen mihi Legio est, quia multi sumus

I'm hyperbolic, hypergolic, viral, chiral. So motherfucking twisted my laevo is on the right side.

fresh1

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Re: Thiophene analog of mephedrone
« Reply #11 on: May 15, 2012, 12:45:54 AM »
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I need good legal stimulant which is not structure analog and little known.
Quote
do you mind me asking why?  Not that I care what you are doing, it's your life you live it, it's just from curiousity

Are you in need of a stimulant or is this more of a synthesis challenge?  :-\

 Just saying,,coz if the legality isn't  absolutely necessary there are much easier ways to go to get one ;)
"Curiosity is a gift"

mildronate

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Re: Thiophene analog of mephedrone
« Reply #12 on: May 15, 2012, 05:58:39 AM »
Its for large scale producing, comercial. Pro drugs of course is very interesting. How about succin imide or saccharin instead of phtalimide?

Adrenaline

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Re: Thiophene analog of mephedrone
« Reply #13 on: May 15, 2012, 04:25:00 PM »
What do you guys think about 2,5-Dimethylmethcathinone? I intend to synthesize this, simply because I have the reagents lying around.
There`s a lot of info around on 3,4-DMMC but the current opinion is, that its not worth trying. How far do you think will the p-dimethylgroup change its activeness?

I also thought about synthesizing the Cathinone analogons of the 2C-X. Theres some information on the 2C-H-Cathinone on bluelight

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I ate about 50 mg of it about an hour ago in a gel cap, and now I feel really good. My knees are bouncing to the music I'm playing, which sounds great. 50 mg feels equivalent to about 100 mg of MDA. I would be dancing if I were in a club. More awake than methylone or MDMA, a feeling not unlike MDMA plus shards--entactogenic but clear-headed with euphoric stimulation. Will have more to report later. (No flames please.)

Do you think they´re worth trying?
« Last Edit: May 15, 2012, 04:26:57 PM by Adrenaline »

Tsathoggua

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Re: Thiophene analog of mephedrone
« Reply #14 on: May 15, 2012, 06:23:26 PM »
Toady would be most interested in bioassaying those. Not the n-methylated versions, but the pthalimide-protected primary amines. Shulgin's 2C-x series and DOX series seemed to lose psychedelic activity when made into secondary amines.
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I'm hyperbolic, hypergolic, viral, chiral. So motherfucking twisted my laevo is on the right side.

fresh1

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Re: Thiophene analog of mephedrone
« Reply #15 on: May 16, 2012, 03:08:25 PM »
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. Pro drugs of course is very interesting
yes very 8)  Its an underexplored field so anything you think of would be good to hear 8)

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succin imide or saccharin instead of phtalimide?

 I'm not sure I understand you...as feedstocks or somehow as possible prodrugs?

Midronatemon do you have access to the precursors you need/might need/want ??? ;) 8) :o   this fact alone makes a huge difference with where you could go although I am not the person to discuss the specifics of hypothetical chemical synthesis, I do come across the odd interesting idea from time to time :D

 I think if you keep posting relevant materials and especially any of your own work, especially if its interesting, ;)  there's a very good chance the wasps who can, will pop in from time to time to comment.

 So thank you for your honest answer midronatemon, much appreciated 8)

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What do you guys think about 2,5-Dimethylmethcathinone? I intend to synthesize this, simply because I have the reagents lying around

 hello adrenaline  :)  matey fresh very much appreciates your honesty here and is happy you are able to have the things needed for such pleasant dreams :)  but at the same time this nest is a fairly friendly place once we get to know you a bit,, it's not the kind of place one can ask for spoon feeding with much hope of getting it  ;)

  That's NOT to say wasps here won't help you with even the simplest or most basic of things, once you have shown us a little about yourself.

 Matey I suggest you introduce yourself at member introductions and read a bit more of the forum to get a 'feel' for it.  In the meantime if you just want to shoot the shit, throw up a topic in the den and see what happens  :o

  anyway welcome mate I like your ideas but I'd like to hear more about exactly what is your starting products and where do you plan on going from there...then all the much smarter wasps than fresh can get their stings into it and who knows what wonderful ideas will appear?  ;D 8)
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2,5-Dimethylmethcathinone (2,5-DMMC) is a stimulant drug briefly reported in 2004 as a designer drug analogue of 2,5-dimethoxyamphetamine, possibly produced in response to the recent popularity of other Substituted cathinone of amphetamines, such as methylone.[1] Anecdotal reports indicate stimulant activity in doses around 50–75 mg lasting for around 16 hours, but proper scientific study has not been done on this compound, and it's availability on the black market was short lived and small scale, so little is really known of its activity or toxicity. More recently, the positional isomer 3,4-dimethylmethcathinone has surfaced on the designer drug market.

btw adrenaline have you or any friends tried this stuff?

cheers all f1 ;)   
« Last Edit: May 16, 2012, 03:16:10 PM by fresh1 »
"Curiosity is a gift"

Adrenaline

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Re: Thiophene analog of mephedrone
« Reply #16 on: May 16, 2012, 04:32:54 PM »
Thanks for your response fresh1 ;)

I really wasn`t looking for any spoonfeeding concerning the synthesis of 2,5-DMMC. Synthesis of cathinones isn`t that hard. ;)
I was just wondering if anyone in here had heard about/ tried 2,5-DMMC, to get a feeling for what im going to deal with. :)
The wikipedia article you quoted is unfortunately misleading. The article is about 2,5-Dimethoxymethcathinone even if it says Dimethyl in the title. Whoever wrote that article obviously made a mistake in the title. If you look at the reference you`ll see that the articel is simply a small summery of the bluelight thread about 2-methylamino-1-(2,5-dimethoxyphenyl)propan-1-one, which is Dimethoxymethacathinone.

This is how i wanted to do it:

Step 1: Friedel-Crafts acylation of p-xylene with propionyl chloride. (AlCl3-catalyzed)
Step 2: Bromination of the 2,5-dimethylpropiophenone to 2-bromo-2,5-dimethylpropiophenone
Step 3: Amination of the bromoketone with Methylamine(aq) in toulene

So my dream is basically going to be kinetics way of synthesizing 4-MMC. :)

Quote
btw adrenaline have you or any friends tried this stuff?

Nope, I don´t know a single person who has tried this cathinone.

cheers
Adrenaline
« Last Edit: May 16, 2012, 04:41:50 PM by Adrenaline »

fresh1

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Re: Thiophene analog of mephedrone
« Reply #17 on: May 16, 2012, 05:01:21 PM »
ok cool thank you for YOUR reply clarifying things and well spotted with the wiki article, nice one  8)  I think you'll fit in here just fine adrenalinemon  ;D 8)

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Synthesis of cathinones isn`t that hard.

  Er no  ;)  Your synth seems fine but as for the molecule no fresh knows of no experiences with this one, let alone dreams  :o

 will look forward to hearing how your synths go matey ,,  if you need help with questions use the short questions thread in 'other chemistry' otherwise so far so good keep up with the interesting posts  ;)

cheers fresh :)

 
"Curiosity is a gift"

mildronate

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Re: Thiophene analog of mephedrone
« Reply #18 on: May 16, 2012, 09:27:39 PM »
Kinetics synth is not very correct, because there is methylamine in product and pirazines is big problem, belive me i tryed :), you need boill water layer with NaOH after reaction. Rotavaping water layer  is bad idea, use reextraction and  HCl gas (or HCl in organic solvent). And in street market mephedrone is mixed with NaHCO3 or phosphates and that way its more potent, because you snuf some free base :D

I need know something more about phtahlimide compounds metabolism. I have no problems with precursors, but i need fully legal compound. Sacharine is used in Gabriel synth and its similar to phtahlimide.  But i was seen only one publication about phtahlimide prodrug, that about "sub coca"

Wizard X

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Re: Thiophene analog of mephedrone
« Reply #19 on: May 17, 2012, 05:57:12 AM »
Albert Einstein - "Great ideas often receive violent opposition from mediocre minds."