Possible PMA/PMMA analogs

[pickle11]

This is my first post to the hive.  I am curious about PMA/PMMA analogs and have found a few references on rhodium's site, here, and in PIHKAL that I think could apply to PMA.  I might be wrong though and would appreciate any advice.  If I
have any dreams that seem realistic enough I'll try to start a PMA analog daydreamer's FAQ.

#1 Nitro-PMA/PMMA

A solution of 7.1g PMA (or 7.7g PMMA) base in 40mL acetic acid was added dropwise over the course of 0.5 hrs to 43mL of 50% nitric acid which was well stirred and cooled with an external ice bath.  The resulting solution was quenched with ice water, made basic with aqueous NaOH,  and extracted with a non-polar solvent.  Dry, Gas, Recrystalize, give .25mg to your neighbors dog, see if he dies, then start upping the dose.

This proposed synthesis was based on

Shulgin's DON synth

(http://www.erowid.org/library/books_online/pihkal/pihkal070.shtml)
In it he mentioned acetamide and formamide derivatives. Were these formed later as another synthesis or during this reaction?  How could a kitchen chemist accompish the hydrolysis?

#2 Iodo-PMA/PMMA

There are two documents on rhodiums site that I thought could be used: 

https://www.thevespiary.org/rhodium/Rhodium/chemistry/doisynth.html

describes a very specific synthesis of 3-iodo-PMA but uses expensive and uncommon silver sulfate whereas

https://www.thevespiary.org/rhodium/Rhodium/chemistry/aromatic.iodination.i2-nitrate.html

uses sodium nitrate (cheaper and easier to get), but is written for anisole.  Would this work on PMA?  Also, it lists the product as 4-iodoanisole.

Where on the PMA would the iodine end up? On the ring? which position?


#3 Bromo-PMA/PMMA

33.3g PMA (or 36.1g PMMA) is dissolved in 500mL of a 3:1 acetone/dH2O solution.  The RXN is cooled to 0C in an icebath with magnetic stirring.  37.3g of 48% HBr(aq) was added, followed  immediately by 23.8g H2O2. the RXN was stirred for six hours, allowing the ice bath to melt. The acetone is removed under vacuum and the residue is dissolved in 0.5-1L dH2O.  The aqueous solution is washed with non-polar solvent (ethyl acetate, toluene, ether), basified to pH 12 with aqueous NaOH, and extracted with 3x200mL portions of ether.  The combined extracts are washed with brine, H2O, and dried over MgSO4. Gas, filter, and recrystalize from IPA/Toluene

This was based on the bromination step in beaker's 2C-B synth, thanks.  It would be nice to  find a synthesis using NaBr, H2SO4, and H2O2. I know it would work but dont know the amounts.

I would test out these drugs by dissolving 1.00g in 100 "units" of a 1cc syringe.  Expel all but 10 units, refill and repeat.  Each unit now contains 0.1mg

[Rhodium]

In any electrophilic substitution of PMA or PMMA, the substituent will end up in the 3-position.

[Osmium]

> 33.3g PMA (or 36.1g PMMA) is dissolved in 500mL of a 3:1
> acetone/dH2O solution.

Do NOT use acetone! You will regret it! bromoacetone is a serious lachrymator, it makes your eyes water like tear gas!

Didn't search the original post you took that from, but I guess the writeup said AcOH. That is acetic acid, not acetone!
I'm not fat just horizontally disproportionate.

[pickle11]

thanks Osmium, it should be 500mL of a 3:1 acetic acid/dH2O solution.

[Chromic]

I tried making 3-br-PMA by brominating freebase PMA in acetic acid with 1 eq. KBr and 2 eq. H2O2 with 2 eq H2SO4. Well, the reaction was easy, the yield about 50%... and the product... boring.

Good luck!

[yellium]

How about the nitro analog?

(Nitro-MDA seems to be quite interesting. Have seen it somewhere on rhodiums page, can't find it now.)

[Rhodium]

I believe you are referring to this document:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/fluoronitro.html

[hypo]

this was more or less coincidence. due to equipment problems nothing interesting could be done and during spring-cleaning some forgotten PMP2P-oxime turned up. so it was reduced with Al/Hg and reacted with 48% HNO3 as in PIHKAL#70 (DON). after recrystallising from EtOH/Acetone: mp=214°C (PMA:208-209°C)

60mg were similar to PMA (not a sign of psychedelia) but much more benign. just that cozy methoxy-amphetamine feeling without much of heart-racing or high blood pressure. after redosing with 50mg first signs of blood-pressure and cardiovascular effects became apparent but again nothing compared to the roller-coaster ride that is PMA.

conclusion: i had expected that a bulky NO2-group would have a much bigger effect on melting point, dosage and effect. but it is definitely not PMA. i think most people will prefer the nitro derivate. personally i think the "wow, i survived"-feeling after a PMA trip is quite appealing, but i'm getting too old for that shit.    the question that remains to be answered is if at higher dosage it will be harsh as PMA or more benign like PMMA. i think the latter.

[Nicodem]

Great! Thanks for sharing the results. In theory it should be 4-methoxy-3-nitro-amphetamine?

...after redosing with 50mg first signs of blood-pressure and cardiovascular effects became apparent...

Could you explain a little more. Does that mean you first took 60mg and a little later (when?) 50mg more or was that in two separate trials?

but it is definitely not PMA

Are you sure? Like you said the m.p. are close, but how about taste, color, TLC or other properties?

[Vitus_Verdegast]

Would you describe the general effects as euphoric, psychedelic, or merely an intoxicated feeling?

I'm abit weary of experimenting with these compounds myself ever since I got migraine headaches from normal doses of PMMA.
What I have been pondering on is N-ethyl-PMA. Has anyone tried this yet?


This is just some loud thinking, but if you look at the PMA molecule, and you compare it with tyramine, one notices that PMA is tyramine with an alpha-methyl group which blocks breakdown by MAO enzymes, and an added methyl ether to help it pass the bloodbrain barrier. So one could speculate that PMA gives exactly the effects that people using MAO-inhibitors want to avoid.

Monoamine oxidase enzyme usually also breaks down tyramine. If an MAO-inhibitor is used, tyramine is not broken down as it usually is, and levels of this chemical build up. Tyramine causes elevation of blood pressure, so an increase in this chemical leads to an increase in blood pressure which could lead to stroke, heart attack, and other nasty side effects. Because of this, people using MAO-inhibitors must avoid foods that are high in tyramine, such as alcohol, legumes (e.g., fava and soy beans), cheese, fish, ginseng, meat, sauerkraut, shrimp paste, soups, and yeast extracts (baking yeast is OK in small quantities).

http://www.afraidtoask.com/depression/depressionmao.htm

It might be a good idea to avoid above foods too when experimenting with it, or with its analogs.

[hypo]

nicodem,

> In theory it should be 4-methoxy-3-nitro-amphetamine?

yes, i think so.

> Could you explain a little more. Does that mean you first took 60mg
> and a little later (when?) 50mg more or was that in two separate trials?

separated by about 1 hour. (duration is short as with all compounds in the
family).

> Are you sure? Like you said the m.p. are close, but how about taste, color,
> TLC or other properties?

i'd say 95% sure. i've had very variable results with PMA, but the one common
thing to all PMA experiences: high heart rate and this sleepy feeling at
the begin of the trip was totally missing.

the chemist needs some serious kick in the ass, because no PMA was prepared
for comparison purposes. taste and appearance are just like every other molecule
in this family. the only way to tell will be a higher dose experiment. the rest
of the research group already announced that they are interested in it, i'm still
a bit sceptical.

vitus,

> Would you describe the general effects as euphoric, psychedelic,
> or merely an intoxicated feeling?

if i have to choose from those 3, i'd take euphoric. but it was mostly body
feeling, so if i can pick something else, i'd describe it as "agreeable".

> What I have been pondering on is N-ethyl-PMA. Has anyone tried this yet?

there's a thread in the general forum, where bwiti said he ingested 1g of
PMEA(sp?) and it did not do much. but as usual his posts are rather cryptic.

> It might be a good idea to avoid above foods too when experimenting with
> it, or with its analogs.

i don't know anything about pharmacology, but i'm willing to avoid those foods (is
there anything you _may_ eat?). the drinks OTOH might pose a problem.    

[Bwiti]

"there's a thread in the general forum, where bwiti said he ingested 1g of PMEA(sp?) and it did not do much. but as usual his posts are rather cryptic."

  What, me? Cryptic posts?  Seriously, what I was trying to say in the gen. dis. is the baggie I received was labeled as "4-MEA". I assumed this to mean 4-methoxy-ethylamphetamine.. What the hell else could it stand for, because I can’t think of anything else?

[_mu_]

4-methyl-amphetamine?
4-methyl-ethyl-amphetamine?
4-methyl-aminorex?