• N&PD Moderators: Skorpio | thegreenhand

Fluorinated amphetamines- dextro & levo

paracelsius

Bluelighter
Joined
Mar 11, 2020
Messages
197
Fluorinated meth(amph)s like 2-FA, 2-FEA, 3-FA, 3-FMA...etc) are more popular than ever. I wonder if the optically pure version of any of those have even been done/tested. Like dextro-3-FMA or dextro-2-FEA....etc
I suppose only one isomer is active if the case of dextro-(meth)amph versus levo-(meth)amph is any indication where dextro is actually the good psychoactive. the other shitty levo isomer only add to cardio side-effects. Sure they wont be cheaper than the racemates so I guess the cartel won't bother separating dextro and the levo.
 
I suspect that a novel resolution methodology would have to be developed. Experience has shown that these fluoroamphetamines are somewhat less soluble than their parent drugs and so appropriate temperatures & volumes of solvent would need to be calculated.

Depending on the synthesis, it's possible to produce them enantiomerically pure with might actually work out to be cheaper. In the case of dexamphetamine, P2P & (1S)-1-phenylethan-1-amine are hydrogenated. Initially 1-phenyl-N-[(1S)-1-phenylethyl]propan-2-amine is formed which on further hydrogenation produces dexamphetamine & ethylamine.

The above is how it was done in the 1960s. Now their are chiral hydrogenation catalysts. Costly but they can be used 40 or 50 times before losing 10% of their catalytic ability (the point at which they are usually replaced).

So it would require investment. I presume Chinese suppliers offer such compounds and experience has taught me that such suppliers are loathe to invest in anything without 100% certainty that they will profit from it.
 
Weird how diphenylprolinol (the pyrrolidine version of pipradrol) was used for synthesis of optically active compounds...
Just commenting.
 
If it’s easier, what about 2-bromo-amp/methamp. 2-chloro, 2-nitro? The 2-fluoro proved to be a great thing. Not revolutionary or anything but 2-fma is nearly as good as dexamp.

3-fa is particularly good, strong and euphoric. 3-fma… somehow sucks (in my opinion but I also think 2-FA is way too weak too).

I wonder if it’s hard to make 2,3-difluoroamphetamines.
 
I don't know if 2-FA has significantly different binding to amphetamine. I think it's mostly the fact that the -F increases the lipophilic character or the molecule and MAY alter metabolism. I would expect a faster onset but I would not guess any more.
 
Weird how diphenylprolinol (the pyrrolidine version of pipradrol) was used for synthesis of optically active compounds...
Just commenting.
there are easier and cheaper routes from L-Proline but it use borane. Not something
Depending on the synthesis, it's possible to produce them enantiomerically pure with might actually work out to be cheaper. In the case of dexamphetamine, P2P & (1S)-1-phenylethan-1-amine are hydrogenated. Initially 1-phenyl-N-[(1S)-1-phenylethyl]propan-2-amine is formed which on further hydrogenation produces dexamphetamine & ethylamine.
The jury is out on that one: whether it is cheaper to just do diastereoisomers separation or use $$ chiral auxiliaries I've seen a pretty neat separation by Hugarians of d and l amph. Stereoselective distillation of one isomer from a salt of racemic amph (acid to make the salt is chiral)!. really neat: just add racemate-distill off isomers one by one... add racemate aging distill off isomer...etc etc I mean you can run on a ton scale without loosing the auxiliary acid
 
there are easier and cheaper routes from L-Proline but it use borane. Not something

The jury is out on that one: whether it is cheaper to just do diastereoisomers separation or use $$ chiral auxiliaries I've seen a pretty neat separation by Hugarians of d and l amph. Stereoselective distillation of one isomer from a salt of racemic amph (acid to make the salt is chiral)!. really neat: just add racemate-distill off isomers one by one... add racemate aging distill off isomer...etc etc I mean you can run on a ton scale without loosing the auxiliary acid
No, I meant it was used as an adduct in the synthesis of a whole range of optically active compounds, not in the synthesis of diphenylprolinol itself. Found it in a chemical catalogue and thought, "that should be a CNS stimulant". Also set thought processes in action that lead to desoxypipradrol...

Although not suitable for industrial scale synthesis, repeat substitution reactions about the chiral atom (is it SN1 or SN2 reactions?) can get you to a chiral end product (at poor yield, at best).
Best if you can get nature to do a pure optically active precursor (like d-pseudoephedrine/l-ephedrine to d-methamphetamine). Makes things a lot easier!
 
I've always preferred DIBAL-H ever since I had a spatula of LAH burst into flames.... I'm not safe to be left around LAH :)
 
Yes - Grignards.... nice organo-metallic chemistry in solvents that will take your head off.

I've read about PCP synthesis and my opinion is that the Chinese are selling the appropriate Grignard (phenyl magnesium bromide) in diethyl ether or THF but labelling it either just as the solvent or possibly as something totally different (which they will readily do).

So just imagine the 'cook' adding the iminium salt (a solid) to the 55 gallon drums which have large overhead stirrers doing their stuff,

The stink, the toxicity and the potential for fire are shocking.

Occasionally the DEA provides images of clandestine labs, and the ONLY images of PCP labs are shells of buildings after fire broke out. Those heavy diethyl ether & THF fumes will fill the workspace and it only takes a spark (faulty wiring, static, improperly grounded items and the MOST common - overloaded supplies) and whoosh!!!!

I HAD presumed that since the original papers from the 60s & 70s, science would have come up with a safer methodology. I mean, surely their must be legitimate chemicals of a similar structure? But no, they all proceed via Grignard or organolithium reactions. Their is theoretically several alternatives but the volume of solvent is huge and they all use Br-CH2-CH2-CH2-CH2-CH2-CH2-Br which I suggest is going to lead to dimers, trimers and polymers... and what I DO know about these people is that they don't put any effort into ensuring that the product is clean.

I was once performing a Grignard in a 3-neck flask. I had used a wired down glass stopper on the neck I wasn't using but it developed a leak. Suddenly a jet of diethyl ether shot up from around the stopper & ignited (I do not know why). I used tongs to hold down the stopper all the time worrying that I couldn't move and that I was within a foot of about 1.5L of 1L of hot ether.

I switched everything off, got the people at adjacent benches to move away and let it all cool... but you can barely see the flame it's so hot.

I suppose we ALL have had one of those scary experiences. It's keeping calm and having a plan. But after that I worked hard with Chemical Abstracts to find alternatives!
 
I suspect that a novel resolution methodology would have to be developed. Experience has shown that these fluoroamphetamines are somewhat less soluble than their parent drugs and so appropriate temperatures & volumes of solvent would need to be calculated.

Depending on the synthesis, it's possible to produce them enantiomerically pure with might actually work out to be cheaper. In the case of dexamphetamine, P2P & (1S)-1-phenylethan-1-amine are hydrogenated. Initially 1-phenyl-N-[(1S)-1-phenylethyl]propan-2-amine is formed which on further hydrogenation produces dexamphetamine & ethylamine.

The above is how it was done in the 1960s. Now their are chiral hydrogenation catalysts. Costly but they can be used 40 or 50 times before losing 10% of their catalytic ability (the point at which they are usually replaced).

So it would require investment. I presume Chinese suppliers offer such compounds and experience has taught me that such suppliers are loathe to invest in anything without 100% certainty that they will profit from it.
what's up with the Rilke picture?? there's more than a bluelighter with it...
 
I found fluorinated amphs way smoother than regular racemic amphetamine. Might be the lower dose but I wouldn’t exclude possibility dextro and levo don’t play nearly as big part as with regular amphetamine. If dextro f-amphs would be even smoother in that case I would prefer them over regular amph any day, if I had an option..
 
I've read that Mexican methamphetamine is sometimes optically pure, sometimes the racemate. They resolved the isomers and kept hold of the (R) since their are papers on how to racemize the product thus one can use half as much BMK to produce the same number of dose units.

I'm most certainly not a fan of methamphetamine. Fencamfamine, 4MAR and phenmetrazine are all good, but methamphetamine... well I just didn't enjoy the experience. Pity because a friend made some and gave me about 6 grams of it... after 30mg I just gave it away.
 
I found fluorinated amphs way smoother than regular racemic amphetamine. Might be the lower dose but I wouldn’t exclude possibility dextro and levo don’t play nearly as big part as with regular amphetamine. If dextro f-amphs would be even smoother in that case I would prefer them over regular amph any day, if I had an option.


Never tried any Psychostimulants apart from caffeine and nicotine, so can’t speak from personal experience. however, I’ve always found it strange that people describe fluorinated amphetamines as more pleasant, calming and cleaner than traditional dextroamphetamine. The only possible scientifically valid reason I’ve heard is that fluorinated amphetamines have significant serotonin releasing activity and this serotonin in turn suppresses/dampens dopamine release. serotonin also has calming/antidepressant and antianxiety effects of its own when released in certain brain regions. basically, fluorinated amphetamines probably still manage to release large amounts of dopamine and so are rewarding/euphoric whilst the serotonin release still restrains the magnitude or decreases The duration of dopamine release. this could decrease negative symptoms of amphetamine use like paranoia and impulsivity.
Since I assume you have experience with both fluorinated and traditional amphetamines, I would be interested to know if you found The fluorinated analogues less reinforcing. i’m interested in this as I read that reinforcement is not necessarily linked to how good a drug feels and I find that a bit strange. nevertheless, I read that serotonin release makes drugs less reinforcing, despite having mood elevating properties.
 
I'm most certainly not a fan of methamphetamine. Fencamfamine, 4MAR and phenmetrazine are all good, but methamphetamine... well I just didn't enjoy the experience. Pity because a friend made some and gave me about 6 grams of it... after 30mg I just gave it away.


As a person who’s never tried traditional psychostimulants, phencamphamine really appeals to me. i’ve read about it before, but I can’t really find any personal experiences so I would appreciate if you could provide your own experience with this drug.
Basically, I’m interested in Phencamphamine because from what I’ve heard, it is a short acting, generally mild and pleasant feeling dopaminergic psychostimulant that is a dopamine reuptake inhibitor. I want to get your thoughts on my future plans to use this stimulant in the following situations.
1: as a functional stimulant to be used on an as needed basis when I’m really struggling to get through boring tasks.
2: on a long-term basis to treat my chronic low mood and anxiety.
3: on an occasional basis for example, when attending large social gatherings where a slight confidence boost and an energy boost would help me fight off my constant urge to fall asleep.

I only ever intend to take this stimulant orally, and to be honest, if I do use it, I think I will stick to occasional use. please note, I’m not asking for a medical diagnosis/Advice, just for some guidance and personal experience, which will help me in my research.
 
Never tried any Psychostimulants apart from caffeine and nicotine, so can’t speak from personal experience. however, I’ve always found it strange that people describe fluorinated amphetamines as more pleasant, calming and cleaner than traditional dextroamphetamine. The only possible scientifically valid reason I’ve heard is that fluorinated amphetamines have significant serotonin releasing activity and this serotonin in turn suppresses/dampens dopamine release. serotonin also has calming/antidepressant and antianxiety effects of its own when released in certain brain regions. basically, fluorinated amphetamines probably still manage to release large amounts of dopamine and so are rewarding/euphoric whilst the serotonin release still restrains the magnitude or decreases The duration of dopamine release. this could decrease negative symptoms of amphetamine use like paranoia and impulsivity.
Since I assume you have experience with both fluorinated and traditional amphetamines, I would be interested to know if you found The fluorinated analogues less reinforcing. i’m interested in this as I read that reinforcement is not necessarily linked to how good a drug feels and I find that a bit strange. nevertheless, I read that serotonin release makes drugs less reinforcing, despite having mood elevating properties.

In my experience with 2FA, 2FMA and racemic Amphetamine, I would say that the fluorinated ones are subjectively less adrenergic.
Not as much vasoconstriction and racing heart in my experience even when dosing over 100mg intranasal in a few hours.
Calmly euphoric and it's possible to focus even on high dosages, while that's completely impossible on regular amphetamine for me.

Ofcourse it might just be that the fluorine makes them a more effective CNS stim due to both isomers crossing the BBB, while levorotary Amphetamine can only target the peripheral nervous system causing high heart rate, vasoconstriction and tremors.
So a racemic amphetamine dose that is subjectively equivalent to a fluorinated analogue will come with a higher body load.

I mean you could be onto something with that higher serotonin release hypothesis, they do are less reinforcing for me than regular amph regardless of me liking the fluorinated ones way more.
Easy for me to have a fluorinated at home and not use it or think of it too much, while with regular amphetamine I basically nose dive into daily use if I have any.
 
Never tried any Psychostimulants apart from caffeine and nicotine, so can’t speak from personal experience. however, I’ve always found it strange that people describe fluorinated amphetamines as more pleasant, calming and cleaner than traditional dextroamphetamine. The only possible scientifically valid reason I’ve heard is that fluorinated amphetamines have significant serotonin releasing activity and this serotonin in turn suppresses/dampens dopamine release. serotonin also has calming/antidepressant and antianxiety effects of its own when released in certain brain regions. basically, fluorinated amphetamines probably still manage to release large amounts of dopamine and so are rewarding/euphoric whilst the serotonin release still restrains the magnitude or decreases The duration of dopamine release. this could decrease negative symptoms of amphetamine use like paranoia and impulsivity.
Since I assume you have experience with both fluorinated and traditional amphetamines, I would be interested to know if you found The fluorinated analogues less reinforcing. i’m interested in this as I read that reinforcement is not necessarily linked to how good a drug feels and I find that a bit strange. nevertheless, I read that serotonin release makes drugs less reinforcing, despite having mood elevating properties.
Yes I found fluorinated amphetamines a lot less reinforcing than regular amphetamine, if that means less fiendish as I think it does. Small amount of 2-fa, 2-fma and I think third was 3-fa but it was quite a long ago so I’m not 100% sure all produced effects I enjoyed but not nearly as much urge to redose. It might be cuz they could be considered less recreational in a sense but that’s not all that’s to it. Last couple times I used amphetamine it was what I was given as a gift and ended up using up all with my ex in a day or so while it could have lasted us for days if used reasonably. But I’m like that a long time with amphetamine, when I used to have a nice stash of it, I would go on a binge usually not lasting longer than 2 days but I would use huge amounts during that 2 days and than not touch it for some time. Funny and sad thing is I’m not even a huge fan of stimulants but tend to be like that with amphetamine and even got addicted to coke, but hey, I’m not a fan of cigarettes either end used to be addicted to them also.

First I tried good amphetamine sulphate I ended up using it for months, most days in a week, sometimes in nice combos, but all the time in rather small doses and never skipping sleep or eating. That was kind of my amphetamine honeymoon. I developed what might be called perma-tolerance but is in reality simply lack of novelty in high amphetamine produces (and it’s quite consistent experience every time you take it). Unlike with some drugs after you get used to amphetamine simply, even doubling the dose doesn’t do the trick like it does with let’s say MDMA (with MDMA you can take 125mg many times and when it starts loosing novelty adding even just 50mg to that amount will produce at least somewhat qualitatively different high and not just increase intensity) but what keeps amphetamine interesting for me is doing loads of it while having sex. One person who used to really be into cocaine always said how doing coke is dull/stupid without sex, for me it’s kinda like that with amphetamine (with maybe another exception being high on it on some party). Unlike him I find coke to be good for sex, in fact as good as any stimulant but I find it great for conversations too, for social occasions that wont lead to neither sex or wild party.

One thing I don’t really like about stimulants, and it’s not a problem with those drugs per se but more with a general culture surrounding them, booze is almost a must for most people when doing them and even tho I used to rather combine them with other stuff, when booze is in front of you on stimulants and you start drinking, that combo removes a lot of bad sides of booze but also mellows out stimulant. Combo of stimulants with other downers makes for a much nicer experience but where I am you’ll certainly be looked down more as junkie if you pop benzos or something with stimulants than down booze with it. While amphetamine makes even a shitty opiate shine better and vice versa (like even “poor man’s speedball” or buprenorphine and amphetamine combo) you can certainly imagine why doing such things will immediately label you as a junkie and is better kept out of sight from most people.

At this point of life I really don’t have much interest in stimulants (lack of sex might have to do something with that, lack of really good stuff too, lack of place to spend energy they would give also) but I certainly wouldn’t mind a good, pure stimulant for a combo with something, but more like an addon than a main component in a combo. Beside in a really specific set and setting and beside a really good stuff without tolerance stimulants alone ain’t really at the top of my list. That has a lot to do with a thing that for me truly uplifting drugs are those that make me anxiety free and that feel great and comfortable for both body and mind. And in occasions many people chose stimulants without thinking I often rather chose some uplifting and “candy” psychedelic, some emphatogen, what most consider downers or dissociative depending on specific set and setting but far from that to say they don’t have their use and that can’t be used for a nice time sometimes. Most people like stimulant high, but no one likes harsh comedowns so that often results in overuse or polysubstance abuse as people develop habit of taking something to ease comedown and at that point I think it’s time to reconsider use of such drugs.
 
I don't think that the NET activity is reduced, rather the SERT is increased which will tend to reduce subjective stimulation. Well, the p-F & m-F certainly. I'm not sure if o-F will elicit increase increased SERT.

But that -F will increase the LogP of the compound and may actually promote hydroxylation of the fluorobenzene ring by activating the 5 position so duration will drop slightly... but it's still crude. I don't think ANYONE who has sampled the 3 stimulants I previously mentioned would touch (meth)amphetamine if they have the choice.

I mean, 4MAR has SERT activity, fencamfamine has mu activity and phenmetrazine has reduced NET activity and so in each case they are much smoother.
 
I'm most certainly not a fan of methamphetamine. Fencamfamine, 4MAR and phenmetrazine are all good, but methamphetamine... well I just didn't enjoy the experience. Pity because a friend made some and gave me about 6 grams of it... after 30mg I just gave it away.

Sounds like you didn't try a euphorigenic dose of methamphetamine 🤔. At low doses (like 30mg) methamphetamine is somewhat dull and not particularly enjoyable. The recreational effects only truly become apparent in doses sufficient enough for the serotonergic effects to shine through.

Granted I'm not a big methamphetamine fan myself but definitely superior to fencamfamine.
 
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