5-MeO-Tryptamine Synthesis From Melatonin

[WillD]

Introduction
The synthesis of 5-MeO-Tryptamine from melatonin is a process of considerable interest within the field of organic chemistry and pharmacology. 5-MeO-Tryptamine, a naturally occurring compound found in certain plants and animals, has garnered attention for its potential therapeutic applications, particularly in the treatment of various neurological and psychological disorders. Melatonin, a hormone primarily known for its role in regulating sleep-wake cycles, serves as a readily available precursor for the synthesis of 5-MeO-Tryptamine. This article explores the synthetic pathway from melatonin to 5-MeO-Tryptamine, discussing key reaction.

Reagents:​

• Sodium hydroxide (NaOH) 40 g;​
• n-Butanol 300 mL;​
• Melatonin (cas 73-31-4) 60 g;​
• Distilled water 100 mL;​
• Isopropanol (IPA) ~300 mL;​
• Hydrochloric acid (conc. HCl 37%) 50 mL;​
• Acetone ~500 mL;​

Equipment and glassware:​

• Round bottom flask 500 mL;​
• Retort stand and clamp for securing apparatus;
• Magnetic stirrer;
• Separatory funnel 500 mL;
• Reflux condenser;
• Glass rod and spatula;
• Heating plate;
• Laboratory grade thermometer (up to 150 °C);
• Laboratory scale (0.1-200 g is suitable);
• Measuring cylinder 100 mL;
• Funnel;
• Filter paper;
• pH Indicator paper;
• Rotovap machine (optional);
• Distillation kit;
• Vacuum source;
• Buchner flask and funnel;
• Beakers 100 ml x2; 250 ml x2;
• TLC kit (optional);

Synthesis Procedures​

1. Sodium hydroxide (NaOH) 40 g flakes are added to n-butanol 300 mL in a 500 mL flask. The mixture is heated up to 80 °C and magnetically stirred for 15 min.
2. Melatonin is added to the flask slowly, a few grams in one portion. Melatonin portions have to be dissolved completely before next portion. All melatonin 60 g is added after a slow sequential addition ~20 min.
3. Thick, highly colored reaction mixture is refluxed at ~110 °C for 2 hours.
4. The reaction mixture is partially solidified after 2 h and become very thick. Some butanol are added in order to re-dissolve a slurry and allow to stir the solution for another 15 min.
5. TLC is taken at this moment and complete conversion of the starting material to product is checked.
6. External heating is turned off, distilled water 100 mL is added. The mixture is stirred for 10 min. The solution is become less viscous and a water layer is separated out.
7. The water layer is separated by a separatory funnel. Then butanol is added back to the reaction flask and distillation is set up. A half of butanol is distilled off until the liquid is become very thick. The mixture is cooled, mexamine free base crystals are formed.
8. Isopropanol (IPA) 50 mL is added to the solution. The flask is heated up to re-dissolve crystals.
9. Hydrochloric acid (conc. HCl 37%) 50 mL is diluted with IPA 100 mL. Acid solution is added slowly to the mexamine mixture in the reaction flask. The mixture is stirred well. The acid is added until pH become acidic (30-40 mL conc. HCl is required) and the solution color is changed to a dark purplish with visible mexamine hydrochloride crystal formation.
10. The mixture is diluted with acetone 100 mL. The flask is placed into a freezer overnight.
11. Crystals are vacuum filtered on the next day, washed with IPA 50mL and acetone 3x100 mL. Product is dried and a silvery grey, sparkly crystalline material 38 g is obtained.
12. A filtrate (IPA and acetone) is concentrated, diluted with acetone and placed into the freezer. The secondary crystals are washed as before (Step 11) and dried to a constant weight 7g. The material is darker, has dull tan and less crystalline than the first filtration batch product. Anyway, this product has an appropriate purity for using in a next step. The recovered mexamine hydrochloride can be recrystallized in isopropanol or ethanol in order to remove the color and by products. 5-MeO-Tryptamine*HCl total yield is 45g (92%).​

 

[Joker_55555]

View attachment 1717
1. 40 g of NaOH prills are added to 300 mL of n-butanol in a 500 mL flask, and brought to 80 C and magnetically stirred for 15 minutes.
2. Melatonin is added to the flask slowly, a few grams at a time, allowing for complete dissolution before adding more. After 20 minutes of slow addition, all the melatonin was added.
3. The now thick, deeply coloured reaction mixture was brought to gentle reflux (temp approx 110 C). And held at this temperature for 2 hours.
4. At the 2-hour mark, the reaction mixture had partially solidified and had become very thick, some butanol was added to redissolve the slurry and aid in stirring for another 15 minutes.
5. At this point, TLC was taken and indicated complete conversion of the starting material to product.
6. The reaction was taken off the heat, and 100 mL of water was added and stirred for 10 minutes, the reaction became considerably less viscous and a water layer separated out.
7. The water layer was separated in a separatory funnel, and then the butanol was added back to the flask and set up for distillation. Half of the butanol was distilled off, until the liquid became very thick. On cooling, crystals were observed to form (freebase mexamine).
8. Some isopropanol (50 mL) was added, and the flask was heated up to redissolve the crystals.
9. 50 mL of conc. HCl (37%) was diluted with 100 mL of isopropanol, and this solution was added slowly to the mixture in the flask, swirling the flask by hand to ensure good mixing. The acid was added, until pH papers read acidic (required 30-40 mL conc. HCl), and the colour of the solution changed to a dark purplish, with visible crystals of mexamine HCl forming.
10. The mixture was further diluted with 100 mL of acetone, and the flask was placed in the freezer overnight.
11. The next day, the crystals were recovered by vacuum filtration, washed with 50 mL of isopropanol, then with 3x 100 mL of acetone, to yield a silvery grey, sparkly crystalline material that weighed 38 g dry.
12. The recovered filtrate was concentrated by distillation, then diluted with acetone and placed in the freezer. The second crop of crystals was washed as before and weighed 7 g dry. The material was darker, and dull tan, and less crystalline than the first crop, but still of adequate purity to be used in the next step. To remove the colour, the recovered mexamine hcl can be recrystallized in isopropanol or ethanol. Total yield: 45 g 5-MeO-Tryptamine HCl (92%).

William DampierHi, the amount of melatonin in this reaction is a few grams

 

[simplechemistry]

700ml of butanol was added to an rbf setup for reflux with an allihn condenser. 60g of KOH was added and the solution was brought up to 80C.
100g of melatonin was added gradually. When done, the solution was brought up to 110C and left there for 3 hours. The solution was checked every 30 minutes.
At one point the solution became very thick and stirring stopped. Butanol was added to redissolve the slurry. After 3 hours, the solution was put off heat and
200ml of water was added and the solution was left to stir for 15 minutes. The solution was transferred to a separatory funnel and the water layer was discarded.
The leftover butanol was concentrated and became very viscous. IpOH was added to redissolve the slurry. Concentrated HCl was added dropwise and the colour of the solution changed to dark purple.
This mixture was diluted with Et2O and put in the freezer overnight. Roughly 92g of 5-methoxytryptamine hcl was obtained which is a yield of 94%.

 

[Bennychairman]

how does the product looks ? is there a picture? my product kinda looks like sand , even after washing few times , crystaline sand

 

[Bennychairman]

View attachment 1717
1. 40g of NaOH prills are added to 300mL of n-butanol in a 500mL flask, and brought to 80*C and magnetically stirred for 15 minutes.
2. Melatonin is added to the flask slowly, a few grams at a time, allowing for complete dissolution before adding more. After 20 minutes of slow addition, all the melatonin (60g) was added.
3. The now thick, deeply coloured reaction mixture was brought to gentle reflux (temp approx 110*C). And held at this temperature for 2 hours.
4. At the 2-hour mark, the reaction mixture had partially solidified and had become very thick, some butanol was added to redissolve the slurry and aid in stirring for another 15 minutes.
5. At this point, TLC was taken and indicated complete conversion of the starting material to product.
6. The reaction was taken off the heat, and 100mL of water was added and stirred for 10 minutes, the reaction became considerably less viscous and a water layer separated out.
7. The water layer was separated in a separatory funnel, and then the butanol was added back to the flask and set up for distillation. Half of the butanol was distilled off, until the liquid became very thick. On cooling, crystals were observed to form (freebase mexamine).
8. Some isopropanol (50mL) was added, and the flask was heated up to redissolve the crystals.
9. 50mL of conc. HCl (37%) was diluted with 100mL of isopropanol, and this solution was added slowly to the mixture in the flask, swirling the flask by hand to ensure good mixing. The acid was added, until pH papers read acidic (required 30-40mL conc. HCl), and the colour of the solution changed to a dark purplish, with visible crystals of mexamine HCl forming.
10. The mixture was further diluted with 100mL of acetone, and the flask was placed in the freezer overnight.
11. The next day, the crystals were recovered by vacuum filtration, washed with 50mL of isopropanol, then with 3x100 mL of acetone, to yield a silvery grey, sparkly crystalline material that weighed 38g dry.
12. The recovered filtrate was concentrated by distillation, then diluted with acetone and placed in the freezer. The second crop of crystals was washed as before and weighed 7g dry. The material was darker, and dull tan, and less crystalline than the first crop, but still of adequate purity to be used in the next step. To remove the colour, the recovered mexamine hcl can be recrystallized in isopropanol or ethanol. Total yield: 45g 5-MeO-Tryptamine HCl (92%).

William Dampier
sorry forgot to quote . my product came out not silver gray buy sparkly yellowish sand in hcl form , does it look correct?

 

[ASheSChem]

it is a precursor ? of what ?

 

[Netflix]

It is 5 meo mipt

 

[Bennychairman]

it is a precursor ? of what ?

ASheSChem
for 5 meo tryptamine sutff , 5 meo dmt , 5 meo mipt , 5 meo dipt and such , i try to make 5 meo mipt trough reductive amination

 

[ASheSChem]

crazy; that's cool

 

[ASheSChem]

and it's only a precursor or we can use in this form?

 

[archae]

It is not active as is, you'll have to use it for something else.

 

[ASheSChem]

ok; thanks

 

[ASheSChem]

5-MeO-Tryptamine HCl

William Dampier

5-methoxytryptamine hcl

this is the same or the second is an other precursor? or a recreational variant?
not evident on google ^^

 

[G.Patton]

this is the same or the second is an other precursor? or a recreational variant?
not evident on google ^^

ASheSChemsame

 

[G.Patton]

sorry forgot to quote . my product came out not silver gray buy sparkly yellowish sand in hcl form , does it look correct?

BennychairmanHi, it looks okay. Have you checked melting point?

 

[Chery]

Would tert-butanol (C4H10O) work?

 

[G.Patton]

Would tert-butanol (C4H10O) work?

ChernobaevI can't answer you for sure.

 

[bblanco]

couple of months ago swim couldnt even replace a light bulp so to say... now i'm obsessed as a lot of substances or not so difficult to create if you just put some effort and energy and near death experiences... kidding..

ok the idiot has arrived.. talking about myself..
1)
"for 5 meo tryptamine sutff , 5 meo dmt , 5 meo mipt , 5 meo dipt and such , i try to make 5 meo mipt trough reductive amination"
to much options on the menu card... i only need to reach 5 meo dmt... just follow Mr Dampiers initial writings?
2) no way Hose you get turn the mimosa based variant into 5MEO right? only through melatonine?
3) what is this what the Chinese offer Dimethylterphalate cas 120-61-6? Just as dmt can be mentioned a dead bird in a box or are there some things to with?

Thanks and enjoy!

BB

 

[csigger]

What can replace n-butanol?
Thanks

 

[HerrHaber]

What can replace n-butanol?
Thanks

csiggerYou know I was wondering the same thing right this very instance for I don't have any close at hand right now. I'm pretty sure I had great success with some MeOH\KOH a.q. 6h reflux, but sadly I don't have my notebook and hence I have no idea about the quantitative ratios nor preparative details. Surely it's a boiling point thing, isobutanol would be the reasonable candidate.