This method is suitable for the synthesis of Mescaline and its analogues (look Pihkal).
Exhaust ventilation, respiratory and eye protection are needed.
- Beakers 25, 50, 100 (x2), 250 и 500 mL
- Reflux condenser 29/32
- Lab support stand
- Hot plate with temperature control
- Magnetic stirrer
- Flat-bottomed flask 29/32 1000, 2000 mL
- Rotary evaporator
- Glass funnel d=100 mm
- Single stage vacuum pump
- Drop funnel 500 and 60 mL
- Litmus test paper (pH 0-12)
- Glass stirring rod
- Bunsen flask 500, 2000 mL
- Buchner funnel d=100 mm
- Filter paper
- Generator of hydrogen gas (dry hydrogen chloride HCl)
- Lab spoon spatula (stainless steel)
- Syringes 20ml (x2)
- Mortar and Pestle
- 3,4,5-trimethoxybenzaldehyde 20g (cas 86-81-7)
- Nitromethane 100ml (for Mescaline synthesis) or Nitroethane 80ml (for TMA synthesis)
- Anhydrous ammonium acetate (AcONH4) 5g
- Methanol 100ml
- IPA 500ml
- THF 350ml
- LiAH 10g
- NaOH 7.5g
- Ethyl acetate 150ml
- Dry hydrogen chloride HCl (gas)
Stage 1/3
Preparation of 3,4,5-trimethoxy-nitrostyrene (for Mescaline) or 3,4,5-trimethoxy-nitropropene (for TMA)by condensation from 3,4,5-trimethoxybenzaldehyde
20g 3,4,5-trimethoxybenzaldehyde + 100ml Nitromethane (for Mescaline) or 80ml Nitroethane (for TMA)
+ 5g Anhydrous ammonium acetate (AcONH4)
Stage 2/3
Reductive amination of 3,4,5-trimethoxy-nitrostyrene/propeneto Mescaline/TMA via LiAH
THF (50ml per 10g) + 3,4,5-trimethoxy-nitrostyrene/propene
250ml THF + 10g LiAH
25ml H₂O
7.5g NaOH
Stage 3/3
Preparation of Mescaline or TMA hydrochloride saltsOil (Freebase) + 150ml Ethyl acetate
Stage 1/3 (00:00-03:07)
The condensation reaction is typical and suitable for the preparation of 1-(2,5-dimethoxyphenyl)-2-nitropropene which is intermediate for the synthesis of a such psychedelic as 2,5-dimethoxy-4-bromoamphetamine (DOB).
20 g of 3,4,5-trimethoxybenzaldehyde is added to the flask 100 mL Nitromethane (for Mescaline) or 80ml Nitroethane (for TMA)
5g Anhydrous ammonium acetate (AcONH4)
Rm is stirred with a magnetic stirrer for 10 minutes
Then Rm is boiled in the round bottom flask (1000ml) with attached reflux condenser for 1-2 hours
The solution is boiled until a deep orange color is reached.
Then Nitromethane (Nitroethane for TMA synthesis) without residue is distilled off in a rotary evaporator
Remember that special hoses have to be used for a vacuum handling. Also, the trap is practically useless in this case.
The nitromethane which was collected in the receiving flask is suitable for further use.
3,4,5-Trimethoxy-nitrostyrene (for Mescaline synthesis) or 3,4,5-Trimethoxy-nitropropene (for TMA synthesis) remain in the flask
They crystallize during cooling
The solution is placed in the freezer. The product crystallize as spectacular crystal needles.
The resulting styrene (or propene) is recrystallized by methanol in a ratio of 1:10
Crystals are filtered and washed with cooled IPA
Do not neglect additional purification at each of the synthesis steps. The purity of the benzaldehyde condensation product significantly affects the quality of the final result.
Stage 2/3 (03:08-09:37)
THF (50ml per 10g) was added to 3,4,5-trimethoxy-nitrostyrene
Stir the solution until the substance is completely dissolved
Rm is poured into the drip funnel
In a flat-bottom flask (2000 mL), 10g of LiAH is gradually poured with 250ml of THF
(optimal use of a two-necked flask)
All reagents and glassware must be absolutely dry. The reaction in the presence of water is unacceptable. A safety violation can cause the mixture to ignite.
Flask immersed into ice water, supplied with reflux condenser and drip funnel
Through reflux condenser, the benzaldehyde condensation product, which was dissolved in THF, is added dropwise to Rm
The reaction is exothermic!
Funnel and reflux condenser are washed with a small amount of THF
Rm is then boiled with attached reflux condenser for 2-4 hours
After a while, the flask is cooled by ice water
Distilled water is slowly added dropwise and the LAH exess are decomposed
It worth to start with 10 ml of distilled water, and than add a NaOH solution (about 15 ml).
Rm pH is corrected with NaOH solution to 11pH
pH measurements are carried out using a glass rod. The glass rod is immersed in the solution and then this glass rod with drop of the solution is touched an indicator paper.
Rm have to be stirred for 10 minutes
Then, the solution have to stay without stirring for one hour until layers are separated
Some chemists leave the solution to stay for 24 hours.
Rm is filtered through paper filter
Vacuum release by a ball valve will significantly extend the life of the pump
After filtration, THF is completely distilled off from the solution
The evaporation of the solvent is carried out in batches or at one time, it is depends on the volume of the rotary evaporator flask.
If condensate is no longer visible in the reflux condenser of the rotary evaporator, it means that all THF was evaporated
The resulting free base can be distilled in a high vacuum for absolutely purity level of the product.
Free base (TMA or Mescaline) is dissolved in a portion of ethyl acetate
The solution have to be dried over the dehydrated MgSO4 (approximately 10 minutes), if a visible water particles are there.
The solution is placed on a magnetic stirrer
Rm have to be cooled and shouldn't be heated during acid is addition.
Stage 3/3 (09:38-11:53)
Mescaline can be crystallized with sulfuric acid, but Mescaline sulfate has a higher dosage
Therefore, gas generator of dry hydrogen chloride gas should be used for Mescaline and TMA
e.g. from sodium chloride and sulfuric acid
The most convenient solution is the using of dioxane hydrochloride
Dioxane hydrochloride, unlike hydrochloric acid, does not contain water
Rm pH is adjusted to 6pH
If the mixture is too thick, it is possible to dilute with a portion of ethyl acetate
The solution exactly equal to 6pH
Rm should now be kept in the freezer for one hour
The final product is filtered
The final product have to be washed with cooled IPA
If you suspend the hydrochloride in a portion of IPA and filter the suspension again, the powder would completely white.
The final yield of mescaline hydrochloride is not less than 19g.
You can find out more about the gas generator here.
The condensation reaction is typical and suitable for the preparation of 1-(2,5-dimethoxyphenyl)-2-nitropropene which is intermediate for the synthesis of a such psychedelic as 2,5-dimethoxy-4-bromoamphetamine (DOB).20 g of 3,4,5-trimethoxybenzaldehyde is added to the flask 100 mL Nitromethane (for Mescaline) or 80ml Nitroethane (for TMA)
5g Anhydrous ammonium acetate (AcONH4)
Rm is stirred with a magnetic stirrer for 10 minutes
Then Rm is boiled in the round bottom flask (1000ml) with attached reflux condenser for 1-2 hours
The solution is boiled until a deep orange color is reached. Then Nitromethane (Nitroethane for TMA synthesis) without residue is distilled off in a rotary evaporator
Remember that special hoses have to be used for a vacuum handling. Also, the trap is practically useless in this case. The nitromethane which was collected in the receiving flask is suitable for further use.3,4,5-Trimethoxy-nitrostyrene (for Mescaline synthesis) or 3,4,5-Trimethoxy-nitropropene (for TMA synthesis) remain in the flask
They crystallize during cooling
The solution is placed in the freezer. The product crystallize as spectacular crystal needles.The resulting styrene (or propene) is recrystallized by methanol in a ratio of 1:10
Crystals are filtered and washed with cooled IPA
Do not neglect additional purification at each of the synthesis steps. The purity of the benzaldehyde condensation product significantly affects the quality of the final result.Stage 2/3 (03:08-09:37)
THF (50ml per 10g) was added to 3,4,5-trimethoxy-nitrostyrene
Stir the solution until the substance is completely dissolved
Rm is poured into the drip funnel
In a flat-bottom flask (2000 mL), 10g of LiAH is gradually poured with 250ml of THF
(optimal use of a two-necked flask)
All reagents and glassware must be absolutely dry. The reaction in the presence of water is unacceptable. A safety violation can cause the mixture to ignite.Flask immersed into ice water, supplied with reflux condenser and drip funnel
Through reflux condenser, the benzaldehyde condensation product, which was dissolved in THF, is added dropwise to Rm
The reaction is exothermic!Funnel and reflux condenser are washed with a small amount of THF
Rm is then boiled with attached reflux condenser for 2-4 hours
After a while, the flask is cooled by ice water
Distilled water is slowly added dropwise and the LAH exess are decomposed
It worth to start with 10 ml of distilled water, and than add a NaOH solution (about 15 ml).Rm pH is corrected with NaOH solution to 11pH
pH measurements are carried out using a glass rod. The glass rod is immersed in the solution and then this glass rod with drop of the solution is touched an indicator paper.Rm have to be stirred for 10 minutes
Then, the solution have to stay without stirring for one hour until layers are separated
Some chemists leave the solution to stay for 24 hours.Rm is filtered through paper filter
Vacuum release by a ball valve will significantly extend the life of the pump
After filtration, THF is completely distilled off from the solution
The evaporation of the solvent is carried out in batches or at one time, it is depends on the volume of the rotary evaporator flask.If condensate is no longer visible in the reflux condenser of the rotary evaporator, it means that all THF was evaporated
The resulting free base can be distilled in a high vacuum for absolutely purity level of the product.Free base (TMA or Mescaline) is dissolved in a portion of ethyl acetate
The solution have to be dried over the dehydrated MgSO4 (approximately 10 minutes), if a visible water particles are there.The solution is placed on a magnetic stirrer
Rm have to be cooled and shouldn't be heated during acid is addition.Stage 3/3 (09:38-11:53)
Mescaline can be crystallized with sulfuric acid, but Mescaline sulfate has a higher dosage
Therefore, gas generator of dry hydrogen chloride gas should be used for Mescaline and TMA
e.g. from sodium chloride and sulfuric acid
The most convenient solution is the using of dioxane hydrochloride
Dioxane hydrochloride, unlike hydrochloric acid, does not contain waterRm pH is adjusted to 6pH
If the mixture is too thick, it is possible to dilute with a portion of ethyl acetate
The solution exactly equal to 6pH
Rm should now be kept in the freezer for one hour
The final product is filtered
The final product have to be washed with cooled IPA
If you suspend the hydrochloride in a portion of IPA and filter the suspension again, the powder would completely white. The final yield of mescaline hydrochloride is not less than 19g. You can find out more about the gas generator here.
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