Author Topic: 4-ACOIndole -> 4-ACOTryptamine -> 4-ACO-DMT  (Read 1623 times)

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trade_om

  • Guest
4-ACOIndole -> 4-ACOTryptamine -> 4-ACO-DMT
« on: July 24, 2004, 04:28:00 PM »
Ive searched and found a synthesis from

indole to trypamine

(https://www.thevespiary.org/rhodium/Rhodium/pdf/indoles2tryptamines.pdf).
The reseachers also claim to have produced 5-benzyloxytrypamine and 6-benzyloxytrypamine.
a bee was thinking of using this mehtod for going from 4-acoindole to 4-acotryptamine, and from that to 4-aco-dmt via KrZ's way.
Here is how the bee thought of doing it -
1. 4-acoindole-3-aldehyde :
 a. Phosphorus oxybromide added dropwise (10cc) to dimethylformamide (35cc) while maintaining a constant stir  and temperatures between 10-20C. A solution of 4-acoindole (17.5g, or 0.1M) in 25ml of  dimethylformamide was added gradually to the first solution, while maintaining temperatures between 20-30C.
 b. The solution was kept at 35-37C for 45minutes-1hour
 c. Then the solution dropped into a stirred solution of ice/water (100g/100cc). sodium hydroxide (19g) in 100cc of water was added gradually over the course of 1/2 hour maintaining 20-30degreesC. the rate of addition - by the     time 3/4 of the solution has been dropped, pH was at 6.    the remainder of the solution was dropped all at once.
 d. Then 200cc of water was added and the mixture boiled for 3 minutes.
 e. The aldehyde collected, washed 5 times with cold water     and dried. Recristalized.
2. 4-Acetoxy-3-2'-nitrovinylindole :
 a. 4-Acoindole-3-aldehyde (3.3g), nitromethane (25cc) and     ammonium acetate (1g) were heated gently to reflux for     1/2 hour. upon cooling the product was fitlered and crystalized.
3. 4-Acetoxy-Tryptamine :
 a. LAH (5g) in ether (250cc) was dropped in a soxhelt     flask. In the thimble the 4-Acetoxy-3-2'-nitrovinylindole was placed (2.4g) and was extracted for 6h. The solution was cooled and 30cc of water were added to decompose the LAH and the additional complex.
 b. The solid was filtered off and washed twice with ether (25cc X 2).
 c. The ethereal solution was dried with KOH and gassed with  anyhdrous HCl. the percipitate was collected, washed with ether and allowed to evaporate.
4. 4-ACO-N,N-DMT : 
 a. 4-aco-tryptamine was reacted according to

KrZ's tryptamine2dmt

(https://www.thevespiary.org/rhodium/Rhodium/chemistry/tryptamine2dmt.html) to give 4-ACO-N,N-DMT.

So the bee has some questions :
Do you bees think this is a feasible and good way to get 4-aco-dmt?
In 1.e where the aldehyde is collected and recrystalized, the paper says that for the 5-benzyloxy equivalent they used ethanol for rextalization. Is it possible to rextalize the 4-aco-equivalent with ethanol?
In 2.a where the 4-aco-3-2'-nitrovinylindole was obtained the paper says to rextalize with benzene or methanol. Could this be done with the 4-aco variation?
In 3.a, where water is added to decompose the LAH, wouldnt this be a bit dangerous? as LAH would react with water?

In 3.c, the paper says to use KOH to dry the ether. I do not get this. Isnt KOH used for adjusting ph and a drying agent is used to dry (like MgSO4)?
And this one is really stupid but please dont flame me - The paper uses Ether. Are they refering to petroleum ether or diethylether?

8)

Rhodium

  • Guest
ethers and esters
« Reply #1 on: July 24, 2004, 04:44:00 PM »
4-acetoxyindole is a labile ester, while the benzyloxy-indoles referred to in the text are stable ethers. Esters will easily undergo hydrolysis and decompose in various ways if subjected to the treatment suggested by you.

In 3.c, the paper says to use KOH to dry the ether. I do not get this. Isnt KOH used for adjusting ph and a drying agent is used to dry (like MgSO4)?

Sure, but KOH has a multitude of uses, among those being an excellent drying agent for ethers as well as being a strong base.

The paper uses Ether. Are they refering to petroleum ether or diethylether?

If not specified further, the term "ether" always refers to diethyl ether.


Lilienthal

  • Guest
4-substituted indoles might also need harsher...
« Reply #2 on: July 24, 2004, 05:44:00 PM »
4-substituted indoles might also need harsher conditions for 3-formylation. It is not possible to generalize recrystallization solvents, they have to be selected for every compound in experiments.

(Beside that it is "4-AcO-N,N-DMT" and not "4aco-nn-dmt"  :P )

Lilienthal

  • Guest
Sure, lithium aluminum hydride reacts heavily...
« Reply #3 on: July 24, 2004, 05:59:00 PM »
Sure, lithium aluminum hydride reacts heavily with water, generating explosive hydrogen gas, but in order to work up the reaction mixture you have to destroy excess reagent  ;D . After this reduction you would have the free 4-OH-tryptamine, which is extremely unstable under basic conditions and will form a nice blue pigment during workup  :) .

trade_om

  • Guest
Argon atmosphere
« Reply #4 on: July 24, 2004, 09:48:00 PM »
The rxn is prefrebly conducted under argon atmosphere, so oxidation or decompostition due to moisture wouldnt take place, but if 4-substituted indoles would need harsher consitions then what could a bee make to make this rxn feasible?
Also, if 4-substituted indoles are unstable under basic conditions then would make it possible to do?
I was under the impression that the 4-hydroxy indoles are sensitive to basic conditions, and not any 4-substituted indole? I thought an acetoxy group would be a nice protector and would not decompose so readily as hydroxy would. I suppose a benzyloxy group would be better...

Rhodium

  • Guest
Protecting groups
« Reply #5 on: July 25, 2004, 01:27:00 AM »
I thought an acetoxy group would be a nice protector and would not decompose so readily as hydroxy would. I suppose a benzyloxy group would be better...

You are fully correct, except that the acetoxy ester is also too sensitive for the suggested reaction conditions. As you say, a 4-benzyloxy protecting group is the way to go, see this procedure:

https://www.thevespiary.org/rhodium/Rhodium/chemistry/psilocybin.html



If you choose the Speeter-Anthony route to prepare your target compoound, the use of 4-Acetoxy-indole is feasible though, see

https://www.thevespiary.org/rhodium/Rhodium/pdf/psilocin-psilocybin.large-scale.pdf




trade_om

  • Guest
New strategy
« Reply #6 on: July 25, 2004, 12:40:00 PM »
OK, so after reviewing and rethinking my strategy, it seems that the route suggested by Shirota, Hakamata and Goda (

https://www.thevespiary.org/rhodium/Rhodium/pdf/psilocin-psilocybin.large-scale.pdf

(https://www.thevespiary.org/rhodium/Rhodium/pdf/psilocin-psilocybin.large-scale.pdf)) going from  : 4-acoindole -> 3-dimethylaminooxayl-4-acetylindole -> psilocin would be a good route. From there it seems that psilocin could be simply acetylated to form the 4-Aco-DMT via the same route on the same paper proposed : 4-hydroxyindole -> 4-acetoxyindole, simply replacing the indoles by dmt.
Does this sound feasible? The bee thinks yes, but the bee isnt sure.