Introduction
There is another catalyst NaBH4 vs. the more selective NaCNBH3. It actually being discarded, without much trial, as producing quarternary tryptamines (β-carbolines) rather than the desired N,N-dimethyl because of a certain mechanism in the Pictet-Spengler reaction. The Pictet-Spengler side-reaction occurs whenever a reductive amination of Tryptamine is performed under acidic conditions (such as HCOOH/HCHO methylation), the reason sodium borohydride usually is disfavored is because it is powerful enough to reduce the formaldehyde to methanol before it has any chance to react with the tryptamine (unless suitable measures are taken to prevent this from happening).
Difficulty rating: 3/10
Equipment and glassware:
- Round bottom flask 1 L;
- Ice bath;
- pH indicator paper;
- Drip funnel;
- Separation funnel;
- Funnel;
- Rotary evaporator;
- Vacuum pump;
- Buchner flask and funnel;
- Beakers 500 ml x3; 200 ml; 100 ml x3;
- Measuring cylinder 200 ml;
- Magnetic stirrer;
- Retort stand and clamp for securing apparatus;
- Laboratory scale (0.1 g-100 g is suitable);
- Freezer;
Reagents:
- Tryptamine hydrochloride (10 g, 62.4 mmol);
- Sodium cyanoborohydride (6.28 g, 100 mmol);
- Methanol 525 mL;
- Glacial acetic acid (11.76 g, 196 mmol);
- Nitrogen baloon;
- Formaldehyde (4.20 g, 140 mmol, 11.05 mL of 38% aq. CH2O);
- Sodium bicarbonate (NaHCO3) aqueous solution;
- Ethyl acetate 275 ml;
- Brine solution 250 mL;
- Anhydrous magnesium sulphate MgSO4 15g;
DMT Synthesis From Tryptamine
Tryptamine to N,N-Dimethyltryptamine (DMT)
1. Tryptamine hydrochloride (10 g, 62.4 mmol) and sodium cyanoborohydride (6.28 g, 100 mmol) in a mixture of methanol (400 mL) and glacial acetic acid (11.76 g, 196 mmol) were cooled to 0°C in the 1 L round bottom flask in an ice bath over a steady stream of nitrogen [note: the stream of nitrogen can be substituted by any other inert gas atmosphere from a balloon].2. A solution of 4.20 g formaldehyde (140 mmol, 11.05 mL of 38% aq. CH2O) in 125 mL of methanol was added dropwise to the solution over a period of one hour with mild stirring.
3. The flask was stoppered, the reaction allowed to cool down to room temperature slowly, and allowed to proceed for the next 60 h.
4. Upon completion the pH was adjusted to 8.0 by the dropwise addition of an aqueous solution of sodium bicarbonate (NaHCO3).
5. The mixture was then extracted with 4 x 50 mL of ethyl acetate.
6. The combined extracts were washed once with brine solution 250 mL and dried over MgSO4 15g for 15 minutes. Magnesium sulphate MgSO4 was rinsed clean with another 75 mL of ethyl acetate.
7. The solvent was reduced to 100 mL on the rotary evaporator.
8. The hot solution was added to a 200 mL beaker and covered with plastic wrap which was sealed on with a rubber band.9. Upon cooling in the freezer overnight, the precipitated DMT was removed by filtration, and dried in the desiccator.
Overall yield is 7.88 g, 45 mmol, 67%. The melting point is around 64-67°C.
Removal of N-Methyltryptamine and Tryptamine from DMT [Optional]
If you're worried about N-MT/T contaminating your product just do the workup this way:1. Basify the aq. reaction mix to 13-14 with NaOH.
2. Extract repeatedly with DCM.
3. Rotovap off the DCM and add petroleum ether, heat to a boil and filter the PE from any undissolved material.
4. Cool PE in the freezer and collect any precipitated solids. This will remove any unreacted tryptamine.
5. To remove NMT you can react this mixture with acetic anhydride and seperate. It's quite inconvenient to handle but it's a good way to cover all the bases as far as purity is concerned.
Sources
- Castro, Jose L., et al. "Synthesis and biological activity of 3-[2-(dimethylamino) ethyl]-5-[(1, 1-dioxo-5-methyl-1, 2, 5-thiadiazolidin-2-yl) methyl]-1H-indole and analogs: agonists for the 5-HT1D receptor." Journal of medicinal chemistry 37.19 (1994): 3023-3032. https://pubs.acs.org/doi/pdf/10.1021/jm00045a006
- https://www.erowid.org