yabee8 (Stranger)
10-18-01 16:51
No 226473
      RXN mech?  Bookmark   


There's a one-pot shot in Psychedelic Chemistry for tryptamine from phenylhydrazine and 4-chlorobutyryl chloride, reflux in EtOH, 90% yield.  Anybody know a mechanism?

If the mech works right, there's obvious paths to other tryptamines via 1,1-dimethyl-2-phenylhydrazine for example.


PS Hi, I'm me :)
(Hive Bee)
10-18-01 19:30
No 226594
      Re: RXN mech?  Bookmark   

IAre you sure you have that right? If its a one-pot-shot to a tryptamine from a phenylhydrazine, then you're talking about the Fischer indole synthesis, but then you'd need to use an acetal of 4-aminobutyraldehyde....er, um, whatever.
10-19-01 00:11
No 226679
      Re: RXN mech?  Bookmark   

Oopses.  PC sez 4-chlorobutyraldehyde, reflux 6 hours in EtOH, 70% yield.  It's the mechanism that's buggin', tho.
(Chief Bee)
10-19-01 07:34
No 226760
      Re: RXN mech?  Bookmark   

Look up the Fisher Indole synthesis. That's the mechanism.
10-19-01 16:16
No 226942
      Re: RXN mech?  Bookmark   

yabee8 lugs out dusty refs...

either i'm totally misunderstanding the fischer indole synth tongue or that can't be it, 'cause there's no catalyst and the product is tryptamine, not indole.  Anybody got CA 79,146321(1973) or CA 80,3381(1974) handy?
10-19-01 16:26
No 226945
      Re: RXN mech?  Bookmark   

J. Org. Chem. 59 3738 1994: They couldn't reproduce that 90% yield and developed a better synth. Search the tryptamine forum for several threads about it.
Check also my reference list: http://www.fortunecity.com/westwood/storey/116/
(Hive Bee)
10-20-01 07:31
No 227156
      Re: RXN mech?  Bookmark   


I think I figured it out. The mechanism behind this is not exactly a straight-forward example of the Fischer indole synthesis (if you haven't looked the Fischer indole synthesis mechanism up already, do so; its on the net.) Instead,  there are a couple other things going on to make it happen. Its creative, though I'm just not convinced it works.

This is the logic behind this "synthesis", as far as I see it: the idea is atomic efficiency. At first glance, there are two things missing from this that make it look impossible: the first thing missing is an acid catalyst to promote the Fischer indole synthesis, the second is the terminal aliphatic amine on theend of the butyl chain (where the chlorine is.) With those two things missing, it looks like there's no way that these starting materials could yield anything like tryptamine.

But, if you stare at it long enough, it all comes into place...

I think they way they're hoping it to work is that the amine leaving group will replace the chlorine, and as this SN2 reaction takes place, an equivalent of HCl (the acid catalyst) is released. The result: there's an acid catalyst in place to promote the Fischer indole synthesis, and an amine dangling off a butyl chain. The reaction seems to depend on some very strange things to take place in order for it to go forward.

Its a cute idea, but I'm just not convinced that it would actually ever work. Like I said, it certainly displays an economy of atoms, but to go through some crazy additional mechanism and obtain an unheard-of, fantastic 90% yield from a Fischer indole synthesis, I'd say this is an example of highly-refined, military-grade bullshit.

In any case, tryptophan is readily decarboxylated to yield tryptamine, so what's the problem? Why not go that route?