Halogenated PEA Confusion/Discussion

[Morninggloryseed]

In the entry for 2C-N, Shulgin says (of 2C-B)..."The 4-bromo group of 2C-B, is a dead-end. It cannot be stretched or compressed or lengthened or shortened."

But fluorine is also a halogen, isn't it? There is 2C-F/DOF, as well as 4-(2-fluoroethyl) and 4-(2-difluoroethyl) substituted psychedelics. So why no 4-(2-bromoethyl) or 4-(2-dibromoethyl) psychedelics?

Oh, while I am at it...any ideas on the activity of, for example, 4-(2-fluoromethyl)-2,5-DMPEA? How about 4-(2-fluoropropyl)-2,5-DMPEA?

Wow, with 4-(2-fluoromethyl, ethyl, and (iso)propyl) substituted PEAs, the difluoro, and trifluoros of each...plus the corresponding alpha-methyl and beta-methoxy homologues for all, coupled with (of course) the N-hydroxys of each does indeed make for a large sub-group of psychedelics. Oh, and each can also exist as a corresponding analogue with the addition of sulfur (as seen the relationship between 2C-EF and 2C-T-21). So (leaving out the beta-ketones, 2-EtO, 5-EtO, and 2,5-EtOs) that makes 144 potentially active psychedelics in this one subgroup!

Just to keep discussion going after this is answered, who else has some (potentially) interesting theoretical halogenated PEAs in mind? I heard of 2,4,5-tribromophenethylamine and 4-methyl-2,5-dibromophenethylamine in another thread. What else should we try in a dream?

 

[fastandbulbous]

Yhe fluoroethyl group is special, in that it alters the electon density in the aromatic ring system in the same way as a halogen, but generally, tagging a halogen at the end of an alkyl chain alters the chemical properties in a way that direct attachment of the halogen to the aromatic ring doesn't. An example being; a halogen on the end of an alkyl chain can react with amines via an substitution reaction, whereas a halogen attached to an aromatic ring can't. This makes haloalkyl groups much more toxic rgan haloaryl groups, as they can act as DNA alkylators (giving tumours etc in some cases). With 2C-T-21, this isn't much of a worry, as fluoroalkyls will only alkylate amines under conditiond that are far more extreme than those ever found in physiological systems. The same can't be said of chloro, bromo or iodo analogues of 2C-T-21 (the heavier the atom, the more likely it is to be an alkylator)

 

[leungkachong]

What Shulgin means is that w/ a halogen attached directly to the 4-position of the benzene ring allows for no continuation. In these cases, the halogen is attached to the alkyl chain used to lengthen.

Plus, DOTFM (the trifluoromethyl substitution) was already made by Nichols in an article about superpotent 5-HT2A agonists (pubmed won't load for me right now :S, reference later).

 

[blase deviant]

I'm not trying to shit on your parade, and this post is entirely off-topic, but I don't like the fact that we're tossing out more and more and more psychedelics when there's barely any research on the ways the ones we have affect the brain, their method of action, etc...

 

[leungkachong]

blase deviant - These are not psychedelics though. To public knowledge, these have not been tasted by man before. They are simply 5-HT2 agonists, and have served the purpose of helping in refinement of the model of receptors involved. The best information on their psychoactivity right now is simply drug discrimination.

 

[fastandbulbous]

but I don't like the fact that we're tossing out more and more and more psychedelics when there's barely any research on the ways the ones we have affect the brain, their method of action

If you were to limit the discussion to psychedelics that were tried and tested, you'd also limit how much can be learned. The way the post reads, you make it sound like were making them available for people to taste (obviously we're not).

A good example is Dave Nichols work with the dragonfly compounds (the conformationally restricted, superpotent 5HT2a agonists mentioned by leungkachong); by making compounds that are essentially planar, other than the phenethylamine side chain, the importance of the planar structure of most of the LSD molecule could be overlooked (and its importance to 5HT2a agonist receptor structure).

It'll also take lots more weird and wonderful compounds in order to fully understand what the 5HT2a receptor is all about.