Some questions on DMT synthesis

[pashov]

Hi!

So I've been researching the DMT synthesis from tryptamine for some time now... And I guess I have got a fair grasp of the processes involved, in theory.
However, lacking much lab expirience, my questions are more general... That's why I'm posting in thsi forum too.

First... Why does KrZ run the synthesis for 60hours, and gets a yield of only 67%, while in "Journal of Medical Chemistry, 1994, vol. 37, No. 19 pg.3029" (as quoted in

https://www.thevespiary.org/rhodium/Rhodium/chemistry/tryptamine2dmt.html

) the reaction runs for about 3 hours and achieves a yield of 83%? That makes me think the workup described in the journal article is somehow superior... But why?

Then it comes to purifying the reaction product...
The journal articles goes:

"Saturated aqueous k2co3 was added and the MeOH was removed under vacuum. The residue was diluted with H2O and the product was extracted with EtOAc twice, washed with salt sol. twice, dried, and concentrated."

I don't understand what's being done there. Why do they add the saturated K2CO3 solution? What will EtOAc not dissolve (thus being useful for purification) and why is the product (with MeOH removed) diluted with H2O first, why isn't extraction with EtOAc possible directly?
And what does the wash with salt solution (do they mean NaCl or K2CO3 by "salt") do?

[Rhodium]

Why does KrZ run the synthesis for 60hours

He is overdoing it (or simply forgot the rxn in the lab over the weekend). Less is much better.

Why do they add the saturated K2CO3 solution?

To neutralize the acetic acid and basify the solution so that the water-soluble DMT acetate salt turns into its freebase form (not soluble in water, but soluble in organics). The reason why potassium carbonate is used instead of the more common sodium hydroxide is that it is a much milder base and you will not risk hurting your relatively sensitive DMT molecule.

What will EtOAc not dissolve?

Inorganic salts and water-soluble byproducts.

why is the product (with MeOH removed) diluted with H2O first, why isn't extraction with EtOAc possible directly?

The MeOH is removed first, as that would otherwise interfer with the extraction, as MeOH is soluble in both water and EtOAc. The water is added to dissolve residual inorganic salts (from the NaBH3CN etc) and other water-soluble byproducts, so that the product DMT can easily be separated from those things by EtOAc extraction. If it was done without water, a way less effective purification would result.

what does the wash with salt solution (do they mean NaCl or K2CO3 by "salt") do?

See

Post 394075 (missing)

(pHarmacist: "Washing with brine", Newbee Forum) (Brine = Salt solution = NaCl_(aq))

[pashov]

Thanks a lot Rhodium! Oh, and one other thing: Is it necessary to do the rxn under an inert atmosphere? KrZ does that, the journal article doesn't mention it.
Oh, and how well does the DMT freebase crystallize from EtOAc?

[yellium]

shitty.

[Rhodium]

If you run the reaction for 60h, then I can understand that an inert atmosphere could be desired, but not if you just let it stir for 3-5h. Use a drying tube filled with CaCl₂ on top of your setup to minimize atmospheric contact.

It is very desirable to flash the crude DMT oil through a short silica gel column, eluting with EtOAc. The resulting purified product crystallizes so much easier (not directly from the EtOAc, evaporate the solvent and recrystallize the DMT freebase from boiling pentane, hexane or cyclohexane).

[yellium]

Ah, so that's the trick... tryptamine crystallizations were much shittier than phenethylamine xtalizations...

[raffike]

So ordinary methylation with Me2SO4 or MeI still works?There has been lot of argueing on that subject

[heavenadisaster]