6-Halogenated LSD

[tycon69]

So I was addyed up writing a physical chemistry lab report and casually browsing structures of psychedelics when I got an idea for a possible new molecule. I was thinking what if someone were to halogenate the 6 position of the indole ring of LSD? If you inspect closely, ignoring the pyrrole of the inner indole ring and a couple other ring structures, one can see the structure of phenethylamine within the molecule. My numbering may not be the best and I can't number it from the entire molecule, but if it were just phenethylamine, the position I am refferring to would be the 4 position. 2c-X phenethylamines have halogen substituents at that spot, and I am curious as to how this would effect the psychoactivity of the molecule or if it would even be stable. Would the size of the halogen cause steric hindrance problems with the nitrogen of the indole structure? I know a synthesis of this would be extremely difficult as their are many other spots that would be succeptible to bromination, but it should be possible (assuming stability) if a synthesis is started from scratch. Would be an expensive endeavor. I looked all over the internet, but all I could find was halogenation at the 2 position of the inner indole ring. Anybody have any ideas/comments?

P.S. I think this is my first post, long time lurker, don't really care to comment very often unless i have something really valuable to contribute.

Thanks

 

[$linky]

You cannot halogenate that bond selectively would be my guess.

 

[sn23]

Yeah my guess is that the halogen would have to be introduced relatively early in a synthesis starting from simple indole compounds (such routes do exist but they aren't very economic of course). I don't know if the halogen would interfere with crucial reactivities needed for synthesis of the lysergic acid scaffold or not, but it is quite possible.

It would be very interesting if these compounds showed psychedelic effects. Nice idea in any case.

 

[sekio]

Like that?

Ring substitutions on the aromatic bit of LSx don't really go well, a brominated LSD analog (BOL whatever) is entirely inactive as a psychedelic, and AFAIK N-methyl lysergamides aren't hot stuff either

Just because LSD contains the skeleton of a phenethylamine, does not mean that it has the same pharmacology.

 

[tryp2fun]

If I recall correctly, 6-substituted DMTs are not psychoactive.

 

[atara]

sekio: that's the 7-position of the indole that you indicated. 6 relative to the indole is to the left; ergolines are numbered in some odd way I don't remember, though it does start with the indole nitrogen. The brominated analogue you're thinking of is BOL-148, the 2-Br analog of LSD; the N-methyl derivative is active only on catabolic demethylation.

Anywho, no, it won't work because LSD binds like a tryptamine, not like a phenethylamine. Pretty much every 6-substituted tryptamine that has been investigated has been inactive.

 

[Dmytry]

what about a fluorinated analogue at the 5 position? fluorine might be small enough that it wont sterically hinder binding, and thats the 7 position seiko