Sciencemadness Discussion Board

Buchwald fischer indole to sub. tryptamines

jwarr - 14-6-2011 at 12:59

Hopefully someone can tell me why this won't work. I've attached the relevant paper. This is mostly mental masturbation, but sometimes it's fun to think about this sort of stuff. None of the precursors are watched/listed except for bromo benzene, but this can be easily prepared.

First, the necessary precursors:
The aryl halide: aryl bromination shouldn't be too hard? Perhaps an excess of benzene to prevent disubstitution.
benzophenone hydrazone: commercially available, cheap, non-watched
The aldehyde: Hydrolyze the acetal, 4,4-Diethoxy-N,N-dimethyl-1-butanamine to the aldehyde. The precursor is commercially available, non watched.

The reaction should proceed smoothly to yield dimethylated tryptamine. My only concern is Buchwald does not have any examples of the reactions with aldehydes. I'd imagine the hydrazone intermediate should still be stable enough for the reaction to proceed, but it's still a bit unnerving.


Attachment: buchwald.pdf (448kB)
This file has been downloaded 1759 times

[Edited on 14-6-2011 by jwarr]

[Edited on 14-6-2011 by jwarr]

[Edited on 14-6-2011 by jwarr]

[Edited on 15-6-2011 by jwarr]

jwarr - 16-6-2011 at 08:05

109 views and not a single reply? Alright, I'll throw in another 2 cents. After some basic research it seems aldehydes are too reactive and as such are used in their protected form. It's unlikely a di-methoxy/ethoxy protection would be adequate given the reaction conditions, and a cyclic acetal is more preferred.

Looks like this probably wont work. After a more careful reading of the paper: "Fischer cyclization of enolizable hydrazones derived from methyl ketones occurs exclusively to the more highly substituted side of the hydrazones (entries 1, 2, 5-7, and 9).6,43 In instances where there is only one enolizable position on the hydrazone, cyclization onto the methyl group carbon does occur to afford 3-unsubstituted indoles"

Does anyone know if the situation would be changed assuming an acetal was used instead?

[Edited on 16-6-2011 by jwarr]