looked up some nice ref's

[element109]

Anyone ever looked into this?
H.DAKIN, BIOCHEM.J. , vol X, 1916

On the oxidation of amino acids to aldehydes and especially nitriles with sodium p-tolylchloramide
and states  phenylalanine-> benzylcyanide in 60% yield

more interesting is the previous paper he refers to, J.Biol.Chem. 1906,
oxidation of amino acids to the corresponding aldehyde & acetic acid  with H2O2 at RT  ,BUT no yield given .
Maybe this is a better way to indole-3-acetaldehyde/acetic acid than the use of NaOCl?

If someone is really interested than i'll care to type 'em out and post here.


e109

[element109]

Shit! I'm sorry it's not phenylalanine but a-amino-phenylacetic acid that gives benzylcyanide in 60% yield.
I surely DON'T want to spread desinformation.
But enough about this, this is tryptamine chemistry.

From Biochem.J. (319-323,1916):
"Recently the writer has been engaged with the investigation of the properties of sulfochloramides such as sodio-p-toluenesulfochloroamide [...] It has already been shown that though a solution of this substance contains no free hypochlorite, it reacts with a-amino acids much in the same way as hypochlorite, yielding aldehydes, CO2 and NH3
[Dakin et al., Proc. Roy. Soc. B.,89,232,1916]. The corresponding aldehydes were prepared from glycine, alanine, leucine, aminophenylacetic acid & methylaminophenylacetic acid. Now sodio-p-toluenesulfochloroamide gives a p^ractically neutral solution and the products of its decomposition are neutral. It appeared therefore that this substance might prove to be a useful oxidising agent suitable for the oxidation of rather unstable substances."

Now the author goes on to state that using TWO molar amounts of sodio-p-toluenesulfochloroamide instead of ONE results in the corresponding nitrile, yields are in the 60-80% range

Knowing that the hypochlorite route is shit b'cause you have to extremely dilute the hypo and concentrate liters of benzene to get a descent amount of unstable product (see Rhodium's for this), could this be a more viable practical way? Sodio-p-toluenesulfochloroamide is cheap and easily obtained.

The other paper i have oxidises the amino acid to a mixture of the corresponding aldehyde and acetic acid with H2O2.



e109

[foxy2]

Definately sounds possible, why don't you give us the procedure and the yields.

I would bet that the procedure on Rhodiums site can be scaled up.  I would try skipping the initial 1200mL dilution and slowly dripping the Hypochlorite into the reaction flask with good stirring.  I would try to regulate the addition so that it is carfully controlled over several hours.  This could allow scaleing into the multiple tens of gram range, if it works.

Do Your Part To Win The War

[element109]

Using undiluted hypo gives a brown product. Maybe H2O2 doesn't?

experimental:
1.0g of alanine was added to the calculated amount of H2O2, neutralised with KMnO4 and standardised with Na2CO3, a few milligrams of ferrous sulfate was added and the solution was allowed to stand overnight. The smell of acetaldehyde increased, and the mixture was distilled in a freezing mix to recover acetaldehyde, residu was acidified and acetic acid w. recovered.
No yields stated, only another ref.

This is also possible with 1:1 molar ratio sodium p-toluenesulfonylchloramide (w/slight heat).

This is all from the head, i don't have much time and don't have them with me now.



e109

[foxy2]

well have we tried diluteing the hypo but not diluteing the tryptophan?  That might bee the ticket?  Slow drip, massive stirring(overhead probably)??

The procedure you posted with H2O2 and KMnO4 seems strange, they are both strong oxidizers, so which one is doing the oxidising?  I would like to have that reference if ya got it.

I like the acetaldehyde synth from alanine, I have been kinda wondering if that would work.  For acetaldehyde you could probably use hypo since the molecule is not nearly as sensitive as tryptophan. 
Anyone make acetaldehyde from alanine? 
Anyone try oxidizing etoh to acetaldehyde, can it bee done?
Hmmm, I wonder what nonpolar solvent would work to extract the acetaldehyde from an aqueaous solution(preferably a high boiling solvent to facilitate distillation)?
I am sure some bee's could find a use for acetaldehyde.


Do Your Part To Win The War

[element109]

No, i think you misunderstood
I don't know why they do the KMnO4-thing but i think H2O2 at RT is the oxidator.
What does worry me is that there aren't any yields stated.

I'm not that interested in acetaldehyde, since I could buy it too if i wish, but couldn't this be applied to more interesting alpha-amino acids like phenylalanine or, more interesting to me and the reason why it's in this forum, indole-3-acetaldehyde or I-3-acetic acid.

The reason why hypochlorite isn't a good way to go is because it will give a mixed product, the chloroamine and the dichloroamine, which decompose to the acetaldehyde and the nitrile respectively.

 R-NH2-COOH  +  NaOCl  ---> [R-NHCl-COONa + R-NCl2-COONa ]
 ------> R-CHO + R-CN (+ R-COOH, oxidation of aldehyde) + NH3 + CO2

As I told before, sodium-p-toluenesulfonylchloramide (used as 'Cloramine-T' as an aquarium desinfectans) seems much more feasible oxidation agent, as 1 mol gives the aldehyde and 2 mol gives the nitrile in good yields (see example above in this thread). What worries me here again is the fact that no yields are stated for the aldehyde, only an isolation procedure. Aldehydes are very reactive so that's why part of it, especially in the case of H2O2, oxidises further into the acetic acid.

BUT that's exactly the beauty here. Indole-3-acetaldehyde is a very unstable critter which could only be stored as the bisulphite addition product, and must be a pain in the ass to work with. But couldn't this be oxidised further in the same reaction vessel, eg. by using a molar excess of oxidation agent, to give (almost) only  indole-3-acetic acid?
ref is:
   H. DAKIN, Journal of Biological chemistry, 1916, p.319

For more details about the chloramine-T reaction i wil dig up this one next week: 
       PROC.ROY.SOC.B. 89,232 (1916),  H.D.DAKIN



Well, I mean, there must be SOMEONE interested in an OTC tryptophan --> I-3-acetic acid way  


e109

[Rhodium]

How about reducing the aldehyde to the alcohol instead, to tryptophol? The tryptophol could then be reacted with tosyl chloride, and the tryptophol tosylate could then be reacted with a dialkylamine directly (or possibly cyanide or azide followed by reduction).

Would tosyl chloride attack the heterocyclic nitrogen?

http://rhodium.lycaeum.org

[Lilienthal]

There is a nice extremly simple new reaction for conversion of aldehydes to nitriles: simply mix your aldehyde with ammonia (you may use THF to dissolve the aldehyde), add I₂ while stirring, wait 5 - 60 min, and extract the nitrile. Yields are usually above 90%.

S. Talukdar et al., Tet. Lett. 42, 1103 (2001)

> Would tosyl chloride attack the heterocyclic nitrogen?

Definitely under breath-of-hoax conditions (CH₂Cl₂, NaOH, TEBAC). Possibly also (but very slowly) without phase transfer catalyst (TEBAC) in the presence of a strong base.

The best way to dialkylated tryptamines is tryptophol ^__> indolyl-ethyl-bromide or -iodide ^__> N,N-dialkyl-tryptamine. Conditions for the conversion to indolyl-ethyl-halogenides are PBr₃ or triphenylphosphine / imidazole / I₂ or Br₂ / CH₂Cl₂ @ RT. The halogenides can be purified by distillation under oil pump vacuum. The major side reaction during the last step of the sequence seems to be the basic dehydrohalogenation.

[Rhodium]

Lili: A while ago you promised to give a detailed writeup on how to go from indole to tryptophol to DMT via indolyl-MgBr. Do you have a heap of refs on the subject?

And is there any specific procedure to follow when brominating tryptophol, or is any PBr3 bromination protocol satisfactory?

http://rhodium.lycaeum.org

[foxy2]

Hmmm
How about this, indoleacetaldehyde and dimethylamine in an Al/Hg reaction?  This is a reaction I have been wondering about for a while.  Easy precursors all the way around.

Or maybe Zn/Hg if a slightly more robust reduction is needed.

Would they react as MDP2P and methylamine do?



Do Your Part To Win The War

[Rhodium]

I'm afraid that the indole-3-acetaldehyde would polymerize under the acid or basic conditions needed for the Al/Hg reduction to work.

http://rhodium.lycaeum.org

[foxy2]

I understand the IAA possibly reacting with the indole nitrogen.

You could have a solution of Al/Hg and dimethylamine(in large excess) and slowly drip in your indoleacetaldehyde solution under heavy overhead stirring.  This would ensure the aldehyde reacts with a dimethylamine before it has a chance to polymerize with the indole nitrogen.
Maybee???

Do Your Part To Win The War

[obituary]

is there a way to reduce the polymerization- even yeilds of 50% would be ok here

and is that aldehyde to nitrile route good for all aliphatic aldehydes? what about aromatics?

[foxy2]

Yea obit thats what I mean
I would actually bee ok with 20%

These are research chems after all

Do Your Part To Win The War

[Lilienthal]

A while ago you promised to give a detailed writeup on how to go from indole to tryptophol to DMT via indolyl-MgBr. Do you have a heap of refs on the subject?

Mee??

I never did it, but I would use 1 equiv. tryptophol and 0.4 - 0.5 equiv. PBr₃ in absolutely dry THF or MeCN. At RT the reaction should be very fast. Work up by partitioning between water / CH₂Cl₂, washing with water, drying the organic phase with MgSO₄, and evaporation.