why 2C-TFM is so potent?

[hugo24]

I remember that bad batch,but what I tasted was 94% pure material.

 

[nanobrain]

i didnt think 2ct-fm that potent, just potently excellent

 

[IGNVS]

you got teh dash in the wrong spot. there is no sulphur in this compound.

 

[nanobrain]

doh!

 

[<pyridinyl_30>]

I've never yet tried 2ctfm, but I was rather impressed with
3-trifluoromethylphenylpiperazine. I would love to taste
3,4-di-trifluoromethylamphetamine. Sadly, fenfluramine (N-ethyl-3-TFM-amp) was shown to cause heart valve defects.

 

[MokumChemist]

I would love to taste
3,4-di-trifluoromethylamphetamine. Sadly, fenfluramine (N-ethyl-3-TFM-amp) was shown to cause heart valve defects.

Slightly OT, but I did try dexfenfluramine before it was withdrawn. Initially, and at lower doses it felt similar to 4-fluoroamphetamine, a bit less stimulating though. Quite pleasant and calmly euphoric, but nothing incredible. Later on, and at higher doses, it became somewhat psychedelic. It even produced some simple OEVs - patterning and colouring over every surface.

Unfortunately I can't remember the dosage because it was years ago. I used it only 3 times, no sign of heart valve damage yet...

 

[stirfry]

Slightly OT, but I did try dexfenfluramine before it was withdrawn. Initially, and at lower doses it felt similar to 4-fluoroamphetamine, a bit less stimulating though. Quite pleasant and calmly euphoric, but nothing incredible. Later on, and at higher doses, it became somewhat psychedelic. It even produced some simple OEVs - patterning and colouring over every surface.

Unfortunately I can't remember the dosage because it was years ago. I used it only 3 times, no sign of heart valve damage yet...

cool. i always had a suspicion that fenfluramine would be interesting in higher doses.

anyone else try it before it was discontinued?

 

[nuke]

Well, the most probable sites of metabolic degradation are supposed to be the amino-function (...MAO), the methoxys (maybe COMT or other methyl transferases) and the CF3. Then again does our body not posess the ability (i.e. the necessary enzymes) to degradade any organic fluorine compound (IIRC). Therefore, metabolism is "reduced" from 3 possibilities (like with 2C-B or alike) vs. just 2 possibilites with 2C-TFM.

So, your "theory" and FnB's statement are not mutually exclusive IMO.

Peace! Murphy

That doesn't explain the duration and potency of 2c-e though, which has quite a few more different routes.

Studies on the metabolism and toxicological detection of the designer drug 4-ethyl-2,5-dimethoxy-β-phenethylamine (2C-E) in rat urine using gas chromatographic–mass spectrometric techniques

The phenethylamine-derived designer drug 4-ethyl-2,5-dimethoxy-β-phenethylamine (2C-E) was found to be mainly metabolized in rats by O-demethylation, N-acetylation, hydroxylation of the ethyl side chain at C2′ or at C1′ followed by oxidation at C1′ to the corresponding ketone, by deamination followed by reduction to the corresponding alcohols or by oxidation to the corresponding acids, and finally combinations of these steps. Most of the metabolites were excreted in conjugated form. The authors’ systematic toxicological analysis (STA) procedure using full-scan GC–MS allowed the detection of an intake of a dose of 2C-E in rat urine that corresponds to a common drug users’ dose. Assuming similar metabolism, the described STA procedure should be suitable for proof of an intake of 2C-E in human urine.

http://www.sciencedirect.com/scienc...serid=10&md5=7b5fd81af0f9ea1ef4475b216b234e7b

You would expect that the iodine in 2c-i would prevent clearance and have a longer duration than 2c-e, but 2c-e seems to run most people longer.

 

[nuke]

In a larger subject. Branched alkanes is lipophilic, maybe good size... It must be a good "4-" substituents! Someone try to put a isopropyl or tertbutyl? I have find no data...

Without going into detail, you could probably get 2c-iP if you substituted one of the beginning chemicals in the synth... Kind of a wonder Shulgin never made it himself, I'm guessing either he didn't have any of the specific acyl chloride around (it's not terribly common) or the there was a problem going by that route. I think the former though, it'd be a neat one to see around.

 

[kidamnesiac]

to make 2ce, shulgin starts with the 1,4 dimethoxybenzene, which is acylated with acetyl chloride and alcl3 to make the acetophenone.
it is impossible to make the corresponding acyl i-propyl chloride, because you have a secondary carbon already and you can't well put a double bonded oxygen and chloride on that carbon (5 bonds). it would make the i-propiophenone, which is equally impossible.
therefore a different, most likely even nastier route than the already-shitty Friedel-Crafts is needed.

ps-One of the labs in my undergrad o-chem experience was making the exact acetophenone described in pihkal. it's kinda fun to do and the yield is reasonable. bottles of the purified material just sat on the shelfs. going all the way to 2ce looks like a real pain.

pps. i hope this isn't too synthetic, as im only discussing what is in pihkal and what is impossible

 

[kidamnesiac]

ppps-sec-butyl seems like a good idea though

 

[nuke]

Rut roh! Yeah, I was thinking the sec or isobutyl as a substitution for the para group...

 

[kidamnesiac]

ah my poor, poor iupac knowledge. only isobutyl is possible for the reason outlined above. sec-butyl denotes the branch is on the carbon beta to the R group

 

[MurphyClox]

That doesn't explain the duration and potency of 2c-e though, which has quite a few more different routes.
...
You would expect that the iodine in 2c-i would prevent clearance and have a longer duration than 2c-e, but 2c-e seems to run most people longer.

Ok, one thing after another.
First, my comment was mainly referring to the duration and not so much to the potency of 2C-TFM.
Second, I admit that I oversimplified the situation a bit. Of course (and here you are absolutely right) there are more than just 2 metabolic pathways available to degradate 2C-E and most probably for 2C-TFM as well.
But: The trifluoromethyl-moiety is a highly unnatural substituent and does everything but facilitate degradation of the compound. Even if the CF3 isn't touched, lets say in a MAO-catalyzed reaction, it does interfere with the substrate's binding to the enzyme. And IMO does that count for probably most (if not all) of the involved metabolising enzymes. This counts in particular for the directly neighboured hydroxy-function (pos. 5) and the meta-postitioned hydroxyl (pos. 2).
In other words: The CF3 makes 2C-TFM an overall bad substrate.

Fig. 2 in the article that you linked (J Chromatograph B 2006, 842, p.76) proposes that the metabolism of 2C-E starts with 4 main reactions (followed by numerous others), one of them involving the pos. 4-ethyl (not working with 2C-TFM!), one with the ortho-hydroxy (hindered metabolism by the CF3), and two involving the amino-function. One of the two latter pathways starts even with acetylation of the amine, a reaction that should
So, I conclude that the CF3-group indeed has (presumably) a major impact on the overall metabolism of 2C-TFM, and thus, slowing down degradation.

About the potency-issue, I can only comment that fluorine has a very special position in nature (...organo-fluorine compounds being the least abundant natural organohalides).
Some examples: There are practically no enzymes known that can handly any F-containing moiety. Fluorine possesses an outstanding electronegativity, paired with it's small size. This implies special properties that are hardly shared by any other element or functional group. I don't want to go too much into detail with fluorine's specialities, but can recommend Science 2007, 317, p.1881 (article avaible upon PM-request) as a good reading for this topic.

With iodine (2C-I) it is different. To my knowledge is the human metabolism able to handle it. Therefore, I would rather expect the iodine-congener getting metabolized faster. And indeed, as you said, most people report about a shorter duration compared to 2C-TFM.

Peace! Murphy

 

[ShadowCatGames]

Ok, one thing after another.
First, my comment was mainly referring to the duration and not so much to the potency of 2C-TFM.
Second, I admit that I oversimplified the situation a bit. Of course (and here you are absolutely right) there are more than just 2 metabolic pathways available to degradate 2C-E and most probably for 2C-TFM as well.
But: The trifluoromethyl-moiety is a highly unnatural substituent and does everything but facilitate degradation of the compound. Even if the CF3 isn't touched, lets say in a MAO-catalyzed reaction, it does interfere with the substrate's binding to the enzyme. And IMO does that count for probably most (if not all) of the involved metabolising enzymes. This counts in particular for the directly neighboured hydroxy-function (pos. 5) and the meta-postitioned hydroxyl (pos. 2).
In other words: The CF3 makes 2C-TFM an overall bad substrate.

Fig. 2 in the article that you linked (J Chromatograph B 2006, 842, p.76) proposes that the metabolism of 2C-E starts with 4 main reactions (followed by numerous others), one of them involving the pos. 4-ethyl (not working with 2C-TFM!), one with the ortho-hydroxy (hindered metabolism by the CF3), and two involving the amino-function. One of the two latter pathways starts even with acetylation of the amine, a reaction that should
So, I conclude that the CF3-group indeed has (presumably) a major impact on the overall metabolism of 2C-TFM, and thus, slowing down degradation.

About the potency-issue, I can only comment that fluorine has a very special position in nature (...organo-fluorine compounds being the least abundant natural organohalides).
Some examples: There are practically no enzymes known that can handly any F-containing moiety. Fluorine possesses an outstanding electronegativity, paired with it's small size. This implies special properties that are hardly shared by any other element or functional group. I don't want to go too much into detail with fluorine's specialities, but can recommend Science 2007, 317, p.1881 (article avaible upon PM-request) as a good reading for this topic.

With iodine (2C-I) it is different. To my knowledge is the human metabolism able to handle it. Therefore, I would rather expect the iodine-congener getting metabolized faster. And indeed, as you said, most people report about a shorter duration compared to 2C-TFM.

Peace! Murphy

I'd say this is very well thought out and aligns with my reserach. I recently received a batch of 2C-TFM (I received an H-NMR with it and a COA, conducted a melting point test also - its the real deal). I found it to be worthwhile if you want to compare and contrast to other 2Cs. Akin to 2C-T-21, based on Shulgin's reports, not personal research (interestingly and obviously another fluorinated compound). 2C-TFM doesn't quite have the magic I had anticipated. A remarkably clear-headed, egoless material. Not exceptionally potent compared to other 2Cs, DOx, NBOMes. I enjoy it of course. High affinity to the 5HT2A receptor doesn't directly translate into "yeehaw." I anticipate that this alone was where the doses on wikipedia got pulled from (comparing affinities to DOx.)

It is active at 3mg, but rats would feel comfortable with 10-15mg for sure, at least IMO. I wouldn't hesitate to push the envelope, other than the fact that there are things working behind the scenes that I might not be aware of. It'll be a slow slow titration to see if there is a breaking point into the rodeo.

 

[Incunabula]

I'd say this is very well thought out and aligns with my reserach. I recently received a batch of 2C-TFM (I received an H-NMR with it and a COA, conducted a melting point test also - its the real deal). I found it to be worthwhile if you want to compare and contrast to other 2Cs. Akin to 2C-T-21, based on Shulgin's reports, not personal research (interestingly and obviously another fluorinated compound). 2C-TFM doesn't quite have the magic I had anticipated. A remarkably clear-headed, egoless material. Not exceptionally potent compared to other 2Cs, DOx, NBOMes. I enjoy it of course. High affinity to the 5HT2A receptor doesn't directly translate into "yeehaw." I anticipate that this alone was where the doses on wikipedia got pulled from (comparing affinities to DOx.)

It is active at 3mg, but rats would feel comfortable with 10-15mg for sure, at least IMO. I wouldn't hesitate to push the envelope, other than the fact that there are things working behind the scenes that I might not be aware of. It'll be a slow slow titration to see if there is a breaking point into the rodeo.

No, It's more likely from this thread:
The-Big-and-Dandy-2C-TFM-Thread

You should ship some of to http://www.ecstasydata.org/ for independent testing. In my opinion vendor HNMR and COA is worthless.

Edit: From what I've been able to read, I would say your doses aren't that far of what other people have found. 5-12 mg seems to be the dose.

 

[Didgital]

There's very few compounds I'm interested in (that's not true but I've tried most), but I am and always have been curious about true 2C-TFM. It surprises me it hasn't become available just due to it's potency and anecdotal reports, maybe it's a lot of trouble isolating as a pure compound.

regardless, its def on my bucket list

 

[AlsoTapered]

Trifluoromethyl arene synthesis by trifluoromethylation

www.organic-chemistry.org

The reagents to swap an aryl I or aryl Br for an aryl CF3 aren't too friendly.

Size and electronic character both have a role in activity but while the exact details have yet to be teased out, RO5 and metabolism are likely other cornerstones of potency and DOA.

It's possible to dick-size over such tiny details. But I'm more interested in things like (R) 7,a-DMT because at no point in TiHKAL did Shulgin ever resolve the enantiomers. He DID in PiHKAL and I presume recognized that one isomer was more or less inactive. Not the case for tryptamines. One isomer has significant 5HT2a affinity, the other is an SRI/DRI making it a potent entactogen... and that 7-methyl is also of huge value as it means that almost all of the material follows a single metabolic pathway which means one doesn't have to consider many metabolites and their potential activity and toxicity.