I've been trying to develop a viable reaction pathway for DET from tryptophan and I think I have one, but I wanted to run it through here to double
check and see if I need to fix anything. Theoretically, one would...
1. Decarboxylate tryptophan in xylene with MEK as a catalyst
2. React said tryptamine with ethyl iodide and sodium carbonate (In much the same way as in the classic DMT synthesis) to obtain a quaternary
triethyltryptammonium salt
3. Stir this in ethanolamine to de-ethylate and form DET
Does this make sense? Am I missing anything? Is there a better way to de-ethylate? Any help at all would be greatly appreciated!
[Edited on 23-9-2020 by SaccharinSlayer]Cou - 22-9-2020 at 19:09
#1 and #2 make sense, but as for #3 I don't know anything about converting quaternary ammonium salts to tertiary amines.
[Edited on 9-23-2020 by Cou]stoichiometric_steve - 22-9-2020 at 23:48
the reaction seems to be sodium thiophenoxyde + ethanolamine
Edit: Nope it isnt't
[Edited on 23-9-2020 by brubei]ArbuzToWoda - 23-9-2020 at 00:32
1. You should probably look for a different decarboxylation method.
Xylene boils a bit too low and MEK is not a suitable catalyst. In reality, one should go with a high boiling ketone like acetophenone and benzyl
alcohol or some natural essential oil ketone like pugelone or carvone (both enantiomers). This saves a lot of trouble in your theoretical scheme.
2. Diethylation by the use of ethyl iodide or bromide with a carbonate as a base catalyst is a well known reaction. The problem is, it's yields are
low, close to 20%. I'm sure you'll find some information about it, as it is nothing hidden. The quaternary ammonium salt forms very slowly unlike in
the matter of methylation.
The ethanoloamine step is therefore unneeded. And even if it was needed, there has been quite a discussion on whether this method - "Breath of Hope",
or more known as "Breath of Hoax" actually works.
Good luck.SaccharinSlayer - 23-9-2020 at 06:53
So I would be forming the tertiary amine in the second step (With 20% yields) and not the ammonium salt. If that's the case then the yields aren't too
much of an issue as tryptamine and ethyl iodide are easy enough to come by for me. It's the ethanolamine that's hard to get. Thanks!
[Edited on 23-9-2020 by SaccharinSlayer]karlos³ - 23-9-2020 at 07:58
I would highly suggest that you use a different base for the ethylation.
Use some organic base, triethylamine for example works as well, not as good as DIPEA, but still much better than a carbonate salt.
Na2CO3 is a bad choice by the way, K2CO3 works better, we had one of ours try it.
I think he still got only like 8% yield or so I believe.SaccharinSlayer157 - 1-10-2020 at 18:35
Forgive me for not knowing exactly how this reaction works or why it is base catalyzed but how much should I use? Should I do a 2:1 molar ratio to
carbonate because triethylamine has half the Brønsted-Lowry base power?
[Edited on 2-10-2020 by SaccharinSlayer157]karlos³ - 1-10-2020 at 19:16
Its not about its "base power" here, otherwise you could use a strong anorganic base.
Why it is base catalysed? Where should the halogen go otherwise?
If you say, to the tryptamines amino group, then where should the second alkylation go? Or, where should it even go without a base and why?
Its actually quite a simple reaction.
The side product is the halide salt of triethylamine or diisopropylethylamine, and you need enough of that amine to act as acid scavenger for two
equivalents of alkyl halide.
And an excess doesn't hurt either, better to use some more to be sure.SaccharinSlayer157 - 1-10-2020 at 20:11
My bad, I was getting dimethyltryptamine and diethyltryptamine chemistry mixed up and forgot we weren't working with an ammonium salt. It all makes
sense now!
