• N&PD Moderators: Skorpio | thegreenhand

Some Interesting 2C-T Analogues (Chemical Masturbation)

given that sulfur tetrafluoride is a good fluorinating agent don't expect an aryl tetravalent sulfur fluoride to be anything less than lethal.
the hexavalent sulfur compound might be less dangerous and more stable. But pretty much sulfur hexafluoride is the only inert and therefore non toxic sulfur fluoride.
 
The SF5 group is listed as a functional group you can use in my medicinal chemistry textbook, but thats the only place i've ever seen it, never come across any drug molecule where its actually been used.

The sigma+ and pi+ factors for the SF5 group are larger than those for CF3, so it is very strongly electron withdrawing and hydrophobic. I'd imagine with all that electronegativity at the 4-position compound D should be highly active, so long as the SF5 group isn't so big it blocks the binding site. 2C-CF3 is very active, but 2C-T9 (with the S-t-butyl group at 4-position) is down in activity by maybe 10x.

So the 4-SF5 derivative might be more potent because of the increased electronegativity, or less potent because of steric hinderance. Other similar substitution schemes that might be interesting would be 4-S-CF3, 4-CF2CF3, 3,4-tris(CF2) etc.
 
Personally, I would steer clear of any Ar-SF5.
It doesn't look healthy.
 
You felt that telepathically, did you see data somewhere to show that, or just a hunch? :)
 
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Inhaling sulfur hexafloride is fun. Your voice goes down 2 octives. Don't do this with gas thats been used because it contains some S2F10 which is deadly.
How to add a -SF5 group? I suspect it might be a total bitch. I think SF5Cl is the way to go.
Link

You might well react the SF5Cl with the -SH to form the appropiate SF5 species and HCl. This species is very unusual but does open up the possibility for, say, -S-CH2-CH2-SF5 which would be an interesting 2CT analog. Someone should ask Sasha if he's thought about this analog. Some friends have his E-mail address but I don't know him personally.
 
haribo1 said:
open up the possibility for, say, -S-CH2-CH2-SF5 which would be an interesting 2CT analog.

It would indeed!

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You know, I was wondering....there is a known active analogue of DOM called DOMCL in which a chlorine atom replaces a hydrogen on the 4-Me. I was told this was bad, as halogens on carbon chains can result in "DNA alkylization." I have no idea if that is true or not, but I've noted so many older sedatives that feature chlorine on a carbon chain. Is that old science, and we know these drugs are now dangerous (many still exist) or is there a chance DOMCL can be brought to light? It seems really interesting to me...I have some of Helio's psychic powers to test new materials and I feel this one could be a winner.
 

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wow !

Very interdesting thread !

A new phenethylamine with an ultimate halogen analog with extreme electronegativity...

Yes the SF5-Ph exist of course http://ambit.acad.bg/ambit/php/display2.php?idstruc=510032 .

This molecule can be extremly potent. the 2C-TFM is very potent with the trifluoromethyl halogen-analog. So I cant imagine the 2C-PFS !!!!

The synthesis way is propably : SF5-Cl + Dimethoxybenzene catalysed with AlCl3.
 
Nice idea MGS. I would imagine that would be a VERY active compound. 2CT21 is pretty damned active but this should be better,
 
From what I've read, SF5Cl is a pretty new reagent. I suspect it's not 'fun' to work with. Starting with SF4, one can make SF5Cl but it's a strong oxidizing agent and is readily hydrolysed to sulfate all the papers on its use are like 2004-2005 so I guess Sasha wouldn't have had this stuff when he wrote Pihkal. I wonder, will it just add right to an -SH? X-S-SF5 would be a mighty big group.
 
morninggloryseed said:
You know, I was wondering....there is a known active analogue of DOM called DOMCL in which a chlorine atom replaces a hydrogen on the 4-Me. I was told this was bad, as halogens on carbon chains can result in "DNA alkylization." I have no idea if that is true or not, but I've noted so many older sedatives that feature chlorine on a carbon chain. Is that old science, and we know these drugs are now dangerous (many still exist) or is there a chance DOMCL can be brought to light? It seems really interesting to me...I have some of Helio's psychic powers to test new materials and I feel this one could be a winner.

Halogens on carbon chains aren't always bad, but they sometimes have a tendancy to break off easily when your body metabolises them, which can generate reactive compounds which can then alkylate DNA or proteins, leading to cancer or anaphylactic reactions respectively. How likely this is depends on the compound used and on the individual's mix of liver enzymes.

Benzylic halogen groups (i.e. Ar-CH2-Cl) are particularly known as alkylating agents (this motif is actually used in some anticancer drugs) and so would not be suitable for use in recreational drugs in my opinion. In fact with a 5HT2A agonist series as discussed such compounds might instead act as antagonists by covalently binding to the active site on the 5HT2A receptor...
 
Would I be right in thinking that the 1 halogen that DOESN'T act as an alkylating agent is F?
I had another thought. What about X-O-SF5?
 
I think the alkylating ability is directly proportional to its tendency to undergo an SN2 reaction. Of all the halogens, fluorine is the worst leaving group, so an aliphatic fluorine would be the least likely to alkylate DNA.
 
Yeah alkyl fluorine groups don't generally act as alkylating agents.

If you see a halogen other than fluorine used in a drug molecule then it was probably invented 20 years ago or more. These days its quite common to always use CF3 instead of Cl and CH2CH2F instead of Br or I, just because your body can't metabolise fluorine, so using fluorinated substituents minimises the chances of unusual adverse reactions (and consequent lawsuits)

That said though there are many widely used drugs with halogens attached that don't appear to cause allergic reactions or DNA alkylation (i.e. valium, many other benzos) so i've always been a bit suspicious that the medicinal chemists that were teaching us were just being over-cautious about it. Certain groups such as Ar-CH2-Cl however are well known for acting this way and i won't be eating any compounds with that motif in the molecule...
 
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I guess this holds generally true. That drug chlormethiazole is the only compound I can think of the top of my head, but then there are other compounds such as trichloroethanol and chlorbutanol for example. PhCH2Cl clearly has resonance stabilization in its conjugate Lewis acid making chloride an OK leaving group.

But aromatic halogens are particularly fascinating. In something like p-iodo-phenyltropane (RTI-55), the compound is so potent that the dose is going to be miniscule. Then there are compounds like 2cb and to a lesser extent 2ci which are not really 'research chemicals' and are known to be relatively safe and well tolerated.

Another good example is in the paper Kozikowski recently published on Nocaine/Modafinil hybrids. After reducing the ester, the alcohol was converted into an iodo-methyl group which was tested and shown to posess considerable activity.
 
morninggloryseed said:
It would indeed!

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You know, I was wondering....there is a known active analogue of DOM called DOMCL in which a chlorine atom replaces a hydrogen on the 4-Me. I was told this was bad, as halogens on carbon chains can result in "DNA alkylization." I have no idea if that is true or not, but I've noted so many older sedatives that feature chlorine on a carbon chain. Is that old science, and we know these drugs are now dangerous (many still exist) or is there a chance DOMCL can be brought to light? It seems really interesting to me...I have some of Helio's psychic powers to test new materials and I feel this one could be a winner.

Here's a improved way of 2C-T-21-SF5 synthesis... I think the real problem is working with SF5Cl. Probably expensive reagent and it's a gas : high pressure or low temperature is required.

What do you think ?
 

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Here's a improved way of 2C-T-21-SF5 synthesis... I think the real problem is working with SF5Cl. Probably expensive reagent and it's a gas : high pressure or low temperature is required.

In this case I think that's about the limit of detail before I have to start weilding a big axe...
 
I would try D, but thats really only because the Pentafloural lambda sulfanyl group looks cool.

Trying drugs because they have cool molecular structure? Sounds like a good method to me! :D


Also MG, jokes aside, you should note that your 7 posts away from the 10k mark! go go go go go go
 
I'm confused here...

In Nichols paper about dragonflys, it has the diagram of 2,5-dimethoxy-4-halo-PEAs, saying the 4 position must have a "hydrophobic region" (IIRC), and isn't SF5 extremely hydrophilic (polar S-F bonds)???

PIHKAL is confusing me more, 2C-F isn't active (at least < 250mg) but DOEF (2,5-dimethoxy-4-fluoroethyl-amphetamine) is active at 2 - 3.5mg! I wonder how DOMF would fair?
 
My money says DOMF (4-fluoromethyl-2,5-DMA) would be more potent than DOM, but not quite as potent as DOEF/DOB.
 
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