Phenethylamines N-methyl-2,5-dimethoxy-4-haloamphetamine?

[KattyKorner]

So has anyone tried an N methylated DOX variant?

Were they seen in pihkal? A quick google didnt give anything that I saw.

I'm just kind of wondering if anyone has pharmacological knowledge and can speculate what the added methyl group could do. The hope would be similar to MDA to MDMA comparison, or even amphetamine to meth, minus more duration lol.

 

[tuppingtoncity]

As for the n-methyl DOM analogue, called BEATRICE by Shulgin; In PiHKAL, there is the following report:

(with 30 mg) “There is a real physical aspect to this, and I am not completely happy with it. There is diarrhea, and I am restless, and continuously aware of the fact that my body has had an impact from something. The last few hours were spent in talking, and I found myself still awake some 24 hours after the start of the experiment. The mental was not up there to a +++, and yet the physical disruption was all that I might care to weather, and exceeds any mental reward. When I did sleep, my dreams were OK, but not rich. Why go higher?”

Clearly active, although peripheral effects seem to outweigh any positives. I believe this caused Shulgin's hesitance towards exploring further N-methylated DOx's much further.

As for the halogenated N-methyl DOx's, Shulgin did go on to synthesize the N-methyl DOB analogue, appropriately named by Shulgin "methyl-DOB". There are two listed reports in PiHKAL:

QUALITATIVE COMMENTS: (with 8.0 mg) “At an hour and twenty minutes, I was suddenly quite light headed. An hour later I must say that the effects are real, and generally good. I am spacey—nothing tangible. And a couple of hours yet later I am still aware. My teeth are somewhat rubby, and as things have been pretty steady for the last three hours, this will prove to be long lasting. There are a lot of physical effects that may be kidding me into providing myself some of the mental. At the sixth hour, I find that this is almost entirely physical. My teeth are tight, there is a general physical tenseness, my reflexes seem exaggerated, and my eyes are quite dilated. All of these signs are lessened by the eighth hour, and do not interfere with sleep at the twelfth hour. There is no desire to proceed any further, at least at the present time. Mental (+) physical (++). Next day, slight impression of persistence of toxicity.”
(with 10 mg) “Nothing psychedelic, but awfully hard on the bod. The next day (24 hours later) I had a severe response to 5 milligrams of psilocybin.”

Again, there appears to be substantially negative peripheral activity with the N-methylated DOx analogues. Shulgin did not, as far as I can find, go on to assay the N-methylated DOC or DOI analogues. Interestingly, Shulgin also synthesized IDNNA (2,5-Dimethoxy-N,N-dimethyl-4-iodoamphetamine), the N,N-dimethylated analogue of DOI. Although, no activity was found up to doses of 2.6 mg (was not assayed at higher doses).

Ultimately, the N-methyl DOx's don't seem too promising as psychedelics... perhaps even mildly dangerous at higher doses?

 

[fuckabout89]

So has anyone tried an N methylated DOX variant?

Were they seen in pihkal? A quick google didnt give anything that I saw.

I'm just kind of wondering if anyone has pharmacological knowledge and can speculate what the added methyl group could do. The hope would be similar to MDA to MDMA comparison, or even amphetamine to meth, minus more duration lol.

They need to make new and completely different one that last long and is extremely powerful without much of the negative effects of regular stims.

 

[xdrc]

There are some N-Et-2C-x which are supposedly active, which I find quite curious.

 

[4DQSAR]

It seems highly likely that N-demethylation takes place (as is demonstrated by every other N-alkyl PEA so in fact those long onsets are simply the result of said enzymatic demethylation.

 

[Esperighanto]

They need to make new and completely different one that last long and is extremely powerful without much of the negative effects of regular stims.

I don't know how much you can separate the DOx experience from the stimulant experience, but you may be more interested in reading the reports of "Eternity", 2C-E-5-Eto. It's a "tweetio" of 2C-E, where the 5-Methoxy substitution in 2C-E was replaced with a 5-Ethoxy, making it milder and much longer lasting. I suspect that this SAR feature would extend out to any 2C, there's no reason to not expect that something like 2C-B-5-EtO or 2C-T-4 with a 5-Ethoxy substitution wouldn't fit what you're looking for. Tragically they're a bit of a bitch to whip up (usually they are only made from rather uncommon synthetic pathways) and most people hate long lasting drugs, so I doubt it would sell well even if they were to be synthesized. I doubt we'll see them on the market any time soon.

 

[fuckabout89]

I don't know how much you can separate the DOx experience from the stimulant experience, but you may be more interested in reading the reports of "Eternity", 2C-E-5-Eto. It's a "tweetio" of 2C-E, where the 5-Methoxy substitution in 2C-E was replaced with a 5-Ethoxy, making it milder and much longer lasting. I suspect that this SAR feature would extend out to any 2C, there's no reason to not expect that something like 2C-B-5-EtO or 2C-T-4 with a 5-Ethoxy substitution wouldn't fit what you're looking for. Tragically they're a bit of a bitch to whip up (usually they are only made from rather uncommon synthetic pathways) and most people hate long lasting drugs, so I doubt it would sell well even if they were to be synthesized. I doubt we'll see them on the market any time soon.

I never got to try the 2C-Bs they sound fun. What was that crazy one bromodragon fly i read about lasts like 3 days.

 

[Esperighanto]

I never got to try the 2C-Bs they sound fun. What was that crazy one bromodragon fly i read about lasts like 3 days.

DOB lasted 104 hours for me once, it's the amphetamine homolog of 2C-B. It would've been about half of that, but halfway through I chiefed the old spice box mod a little too hard and it restarted the trip.

 

[4DQSAR]

I don't know how much you can separate the DOx experience from the stimulant experience, but you may be more interested in reading the reports of "Eternity", 2C-E-5-Eto. It's a "tweetio" of 2C-E, where the 5-Methoxy substitution in 2C-E was replaced with a 5-Ethoxy, making it milder and much longer lasting. I suspect that this SAR feature would extend out to any 2C, there's no reason to not expect that something like 2C-B-5-EtO or 2C-T-4 with a 5-Ethoxy substitution wouldn't fit what you're looking for. Tragically they're a bit of a bitch to whip up (usually they are only made from rather uncommon synthetic pathways) and most people hate long lasting drugs, so I doubt it would sell well even if they were to be synthesized. I doubt we'll see them on the market any time soon.

Resolve the two isomers?

I cannot remember if Shulgin resolved all of those DOx compounds. I seem to remember he did resolve one and concluded one was responsible for most of the activity which isn't the same as saying that the two may be more than a sum of their parts.

I'm thinking here of the stimulant activity. If only because the 2,5-diomethoxy derivative of PPA (methoxamine (INN][BAN] Vasoxin™/Vasoxyl™/Vasoxyl™) was apparenly used in general anesthesia to treat hypotension and was the raecemate, but it is/was classed as a long-acting α1-adrenergic receptor agonist.

But I just noticed the closely related butaxamine which is chiral and apparently a β2-selective beta blocker and 3-MeO derivative of epinephrine is also use to treat hypotension (shorter duration of activity being the advantage but is also an α1-adrenergic receptor agonist).

You know, this may infer why some users find 5-MeO derivatives of the trypamines produce the feeling of 'being sat on by an elephant' (I believe Shulgin was first to say words to that effect). The α1-adrenergic receptor agonist activity. My hypothesis, I hasten to add. But nobody has undertaken a study to find out. No money in publishing the fact that you product is toxic, I guess. Of the O-desmethyl metabolite, not just the active itself.

Fascinating to see how the shillers are massively bigging up 5-MeO DMT which unlike plain DMT has KILLED people with criminal proceeding taken against those promoting it's use as part of their $2000/day 'retreats'. All I can remark on that topic is that in Amsterdam where both were freely available, DMT cost considerably more and dodgy dealers were adding 5-MeO-DMT to real DMT to increase profits. I know this because as always, I got the NMR/GC-MS pairs on quite a few samples. So given the choise, people preferred DMT by a huge margin.

In fact, my limited experience of 5-MeO-DMT is why I passed on the offer of free 5MeO-AMT. It was in the form of a green gel so my very first question was 'why is it green' as I KNOW 5-MeO-AMT to be a while powder.

But back to the plot. I also hypothesized that since 2C-N was considered similar but inferior to MDMA, could resolving DON produce something more akin to MDA? That 4-nitro is almost unique as ayl nitro compounds are zwitterions. I am unaware of any recent research into DON because it is not a rewarding synthesis and losing the more potent half of your product would go against anyone with laser-like focus on profits. In this single case, the N-methyl would at once reduce potency still more BUT may potentially make it more like MDMA than MDA. After all, it's only a partial (low effaciacy) agonist at the 5HT2a receptor, has affinty for the serotonin receptor.

Sci-Hub: are you are robot?

Sorry the reference is so old. I just feel it's one of the least explored even when 2C-N apparently suggests it's at least as likely to be an entactogen than hallucinogen and like AMT may have a window offering both much like MDA. You can't patent it unless it's for specific ratios of the isomers, a novel polymorph and/or the fact nobody appears to have synthesized the N-alkyl derivatives of the parent.

 

[Esperighanto]

Resolve the two isomers?

I cannot remember if Shulgin resolved all of those DOx compounds. I seem to remember he did resolve one and concluded one was responsible for most of the activity which isn't the same as saying that the two may be more than a sum of their parts.

I'm thinking here of the stimulant activity. If only because the 2,5-diomethoxy derivative of PPA (methoxamine (INN][BAN] Vasoxin™/Vasoxyl™/Vasoxyl™) was apparenly used in general anesthesia to treat hypotension and was the raecemate, but it is/was classed as a long-acting α1-adrenergic receptor agonist.

But I just noticed the closely related butaxamine which is chiral and apparently a β2-selective beta blocker and 3-MeO derivative of epinephrine is also use to treat hypotension (shorter duration of activity being the advantage but is also an α1-adrenergic receptor agonist).

You know, this may infer why some users find 5-MeO derivatives of the trypamines produce the feeling of 'being sat on by an elephant' (I believe Shulgin was first to say words to that effect). The α1-adrenergic receptor agonist activity. My hypothesis, I hasten to add. But nobody has undertaken a study to find out. No money in publishing the fact that you product is toxic, I guess. Of the O-desmethyl metabolite, not just the active itself.

Fascinating to see how the shillers are massively bigging up 5-MeO DMT which unlike plain DMT has KILLED people with criminal proceeding taken against those promoting it's use as part of their $2000/day 'retreats'. All I can remark on that topic is that in Amsterdam where both were freely available, DMT cost considerably more and dodgy dealers were adding 5-MeO-DMT to real DMT to increase profits. I know this because as always, I got the NMR/GC-MS pairs on quite a few samples. So given the choise, people preferred DMT by a huge margin.

In fact, my limited experience of 5-MeO-DMT is why I passed on the offer of free 5MeO-AMT. It was in the form of a green gel so my very first question was 'why is it green' as I KNOW 5-MeO-AMT to be a while powder.

But back to the plot. I also hypothesized that since 2C-N was considered similar but inferior to MDMA, could resolving DON produce something more akin to MDA? That 4-nitro is almost unique as ayl nitro compounds are zwitterions. I am unaware of any recent research into DON because it is not a rewarding synthesis and losing the more potent half of your product would go against anyone with laser-like focus on profits. In this single case, the N-methyl would at once reduce potency still more BUT may potentially make it more like MDMA than MDA. After all, it's only a partial (low effaciacy) agonist at the 5HT2a receptor, has affinty for the serotonin receptor.

Sci-Hub: are you are robot?

Sorry the reference is so old. I just feel it's one of the least explored even when 2C-N apparently suggests it's at least as likely to be an entactogen than hallucinogen and like AMT may have a window offering both much like MDA. You can't patent it unless it's for specific ratios of the isomers, a novel polymorph and/or the fact nobody appears to have synthesized the N-alkyl derivatives of the parent.

I expect that even isomerically resolved, it would still be rather stimulating. As far as the 2,5-dimethoxy-4-nitro compounds go, they are not that tough to make, they share a synthetic route with the 4-halogenated compounds but differ by a single reagent. I've only had DOB that was allegedly isomerically pure, but until I'm isomerizing these things myself I won't really trust it.

 

[4DQSAR]

Resolve - isomerization would need to step back to an achiral intermediate. As part of isolating the enantiopure product it only make sense if part of an MER stratergy.

That's my point, the LESS potent (S) enantiomer is the one of interest.

Also, is 2,5-dimethoxy amphetamine an item of commerce? Because I've gone from the benzaldehyde and it was a non-trivial process. Even resolving the two isomers is a bit of a pain.

Sure, there ARE a few chiral reductions of nitroolefins and the nitroalkanes, but the ee is only about 38% at top whack. So not facile if you want one isomer as you would still need to resolve to get rid of the more active isomer. So yes, slighly more molar efficient; even more work.

But so far nobody has tried this so I mention it purely as a hypothesis and then slowly worked though the logic of why it MAY be a overlooked gem. But only MAY - I apologised for the lack of more recent papers but could find no more and while only weak evidence, it is evidence.

But hey, it you have access to exquisite technologies that make it a trivial matter - go right ahead and let us know how it all went. Sure, maybe there is some novel way to nitrate but all the methods I am aware of are non-trivial.