Author Topic: transamination with pyrillium salts  (Read 1483 times)

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  • Guest
transamination with pyrillium salts
« on: March 21, 2002, 11:53:00 PM »
Forgive me for I am not sober!!!
Was reading this :

and came up with an idea:
(not really related to the article)

1. prime amine is converted to pyridinium salt via reaction with 2,4,6-trimethyl-pyrillium  (246TMP) clorate.
Example : tryptamine + 246TMP -> N-[2-(indol-3-yl)-ethyl]-2,4,6-trimethyl-pyridinium (Tryp246TMP)
Note: 2,4,6-pyridine is good leaving group, it seems.

2. Nucleophilic substitution with dialkyl amine.
Example: Tryp246TMP + [CH3NHCH2CH3]
__> N-methyl-N-Ethyl-Tryptamine
I guess, one can do "cold version" with corresponding
sodium dialkyl amide (e.g. Na[CH3NCH2CH3])

General Note: seems that it would be the best method
for convertening -NH2 into good leaving group in the case of indole derivatives;
oxidative methods, (e.g. -NH2 -> -N2+, etc.) usually mess
up pyrrol ring nitrogen as well, turning it into N-0 radical


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  • Guest
pyrillium-pyridium salts
« Reply #1 on: March 22, 2002, 05:03:00 PM »
an interesting idea Z_hound,  this is a fairly universal reaction with many variations, but afaik no one has reported trying it with tryptamine.

the major down side is that the creation of the pyrillium salt is awkward, either one creates the perchlorate salt which is rather unstable and explosive, or one uses the tetraflouroborate salt which involve the use of BF3 etherate or fluoroboric acid both of which are very corrosive to glass, and rather toxic. I don't know whether perchlorate salts oxidise indole it seems a strong possibility.
Other pyrillium salts with better non nucleophilic counter ions may have been developed since my days in a lab if anyone knows of them speak now. 

a few variations are none of them overcome the awkward problems:

1 substitute a different pyrillium salt the 2,4,6 triphenylpyrillium salts are good as they create even better leaving groups than the trimethyl compounds and are easily synthesised from acetophenone and benzaldehyde.

2 produce a tryptyl halide (indole ethyl bromide for example) by treating tryptamine with a pyrillium bromide salt and heating the resulting pyridium bromide salt, this has the advantage of enabling purification of the intermediate halide. treatment of tryptyl halide with aqueous dialkylamine produces the desired tert amine

creating a good leaving group from -NH2 using the pyrillium-pyridium doesn't seem to be as good as converting the NH2 group to an NN ditosyl group. NB depending on the base used the indole 1 nitrogen can reacts as well so tryptamine would become the 1, NN, -tritosyl derivative. treatment of this with dialkylamine would give the nn dialkyl 1 tosyl tryptamine and hydrolysis of the 1 tosyl group with acid would give the nn dialkyl trytamine salt.
Having said all that the pyrillium pryridium method is certainly much better than the use of nitrous acid.   


  • Guest
« Reply #2 on: March 25, 2002, 10:42:00 AM »
I liked #2, that sounds feasible.

 good non-nucleophilic group can be F3CCOO-, i think;
which is easy to get too. triphenyl pyridinium sounds nice;
I beleive products can be separated based on their differences in pH (titration/electrophoresis?)

Hmm, with agarose gel you go as high as pH 10, i guess some other matrix can be used if I d need higher pH.
that would be cool! - If instead of some silly proteins I would separate amines on the gel...

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  • Guest
more on nitrous acid.
« Reply #3 on: March 25, 2002, 06:15:00 PM »
Is it possible to get indol-3-yl-methyl-carben from tryptofan by treatment withnitrous acid ( or NaNO2, HCL)
this carben, I bet can find its use, for future (yr. ~2025?) one-step synthesis of dmt from tryptophan

Imagine this:
indole-3-yl-CH2CH(NH3+)COO-  +NaNO2/H+ ---------> indole-3-ylCH2CH(N2+)COO-
indole-3-yl-CH2CH: +H-N(dialkyl) ----> indole-3-yl-CH2CH2N(dialkyl)
or, indole-3yl-CH2CH: + ON-N(dialkyl) ------> indole-3-yl-CH2CH2N(dialkyl) + NO; this  ON-N(dialkyl) can be made from HN(dialkyl) in the same pot...  (i beleive it it the result with nitrous acid with dialkyl amines, right?)
If I were motivated, I would right a grant for that!
well, most probbaly it will react with itself, forming indole-3-yl-HC=CH2,
and products of addition.
one could protect indile N-H with benzyl-halide, I guess, if any problems.



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