Methamphetamine Synthesis. Leuckart Method From P2P.

GhostChemist

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The reactions proceed according to Scheme 1
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Reagents and materials:

  • 1-Phenyl-2-propanone (P2P) 5.4 ml;
  • N-methylformamide 13.4 ml;
  • Sodium sulphate (Na2SO4);
  • Hydrochloric acid (14% aq HCl) 32.1 ml or 20 ml 44% sulfuric acid H2SO4;
  • DCM 100-150 ml;
  • Sodium hydroxide (NaOH) 9,6 g in 24 ml H2O;
  • Sodium hydroxide (NaOH) 7.5 g in 30 ml H2O;
  • Ethanol 88% 10-15 ml;
  • Distilled water 100 ml;
  • Diethyl ether 5-10 ml;
  • Acetone 5-10 ml;
  • Hydrogen chloride gas (HCl);
  • Flasks;
  • Beakers;
  • Reflux condenser;
  • Hydrogen chloride gas generator;
  • Heater;

Execution of synthesis

N-methylformamide is added to P2P, a reflux condenser is attached. The mixture is heated to 165-170°C and refluxed at this temperature for 36 hours.

The initial components are N-methylformamide and P2P. Fig 1

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Mixture of N-methylformamide and P2P. Fig 2

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The reaction mass reaches a temperature of 160°C. Fig 3

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The reaction mass after 1 hour of heating at the specified temperature. Fig 4

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The reaction mass, after 18 hours of heating at the specified temperature, turns red. Fig 5

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After 36 hours, the reaction mixture is cooled to room temperature. Then, 9.6 grams of sodium hydroxide dissolved in 24 ml of water is added, and the reaction mixture is refluxed for 2 hours with vigorous stirring. There is a significant release of methylamine or ammonia, even upon loading 5 grams!!! Fig 6

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After 2 hours of boiling, the reaction mixture is cooled to room temperature and separated into different layers. Fig 7

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An aqueous layer is discarded. Hydrochloric acid 32.1 ml (14% aq HCl) or 20 ml 44% sulfuric acid H2SO4 is added to a red organic layer. Fig 8

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The mixture is boiled under a reflux condenser for 2 hours. After boiling, the color changes to dark green when treated with hydrochloric acid, while it remains brown when treated with sulfuric acid. Fig 9
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Then, the solution is cooled to room temperature. The desired aqueous layer is separated, and the organic layer is further washed with water. NaOH solution (7.5 g in water 30 ml) is added. After the addition of the alkali, the color turns brown again. Fig 10
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Methamphetamine is extracted from the aqueous layer with several portions of DCM. Fig 11

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The DCM layer is dried with anhydrous sodium sulfate and filtered through a paper filter. Fig 12

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DCM is distilled off at a temperature of 90°C. Fig 13

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In the flask, there remains a brown oil of the free base with a characteristic amine odor. Fig 14

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The obtained free base is dissolved in ethanol and saturated with hydrogen chloride until a strongly acidic reaction is achieved. The color of the solution should also change to raspberry. Fig 15

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The resulting solution is evaporated to crystallization. Ultimately, a brown mass is obtained. Fig 16

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Subsequently, the mass is fully crystallized. Fig 17

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To the obtained crystallized mass, a small volume of diethyl ether is added, and it is transferred to a porous filter. Only one diethyl ether washing doesn't yield a pure product. Fig 18

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Further washing with even strongly cooled acetone does not yield an absolutely pure product and leads to significant losses due to its high solubility. Fig 19
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The final powdery product is the hydrochloride methamphetamine salt. Fig 20
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Due to the fact that the final product is heavily contaminated, despite using initially purified P2P, an analyzing of the obtained data recommends (especially for larger loading volumes of 50 g P2P and more) mandatory steam distillation of the obtained methamphetamine free base after DCM extraction. This will help to avoid significant additional losses. Additionally, based on the conducted experiments, it should be noted that hydrolysis with sulfuric acid is more convenient and prevents its volatilization during boiling, unlike hydrochloric acid.

The yield of the hydrochloride (hydrolysis with hydrochloric acid) after washing with diethyl ether and acetone is 2.3 g or 30.8%.
The yield of the hydrochloride (hydrolysis with sulfuric acid) after washing with diethyl ether and acetone is 2.4 g or 32.1%.
When using steam distillation of the free base after the removal of DCM, the yield of the free base is 2.3-2.4 g or 38.3-40%.

Subsequent yield of the hydrochloride is 2.7-2.8 g or 36.2-37.5%.
 

CryoThio

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The leuckart is so simple, but the yields are absolutely garbage.

If people could figure out how to increase yields, this would help the clandestine chemistry community so much.

Apparently magnesium chloride can be used as a catalyst, from what I've gathered online, maybe that will help yields a few percent points.
 
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G.Patton

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The leuckart is so simple, but the yields are absolutely garbage.

If people could figure out how to increase yields, this would help the clandestine chemistry community so much.

Apparently magnesium chloride can be used as a catalyst, from what I've gathered online, maybe that will help yields a few percent points.
CryoThioWe carried out own experiments and now can say for sure about yield, there is synthesis report.
 

41Dxflatline

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The leuckart is so simple, but the yields are absolutely garbage.

If people could figure out how to increase yields, this would help the clandestine chemistry community so much.

Apparently magnesium chloride can be used as a catalyst, from what I've gathered online, maybe that will help yields a few percent points.
CryoThioA Brief Review: Advancement in the Synthesis of Amine through the Leuckart Reactionby Qasim Umar and Mei Luo

There you go, massive increases in yield and also speed.
 

CryoThio

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A Brief Review: Advancement in the Synthesis of Amine through the Leuckart Reactionby Qasim Umar and Mei Luo

There you go, massive increases in yield and also speed.
41DxflatlineI'm a complete beginner, but I'm looking at the paper, and they have a part that is showing how much ketone they used, formic acid, and the catalyst.

The notation they used confused me. They had 3.00 mmol, exactly as written, for the ketone 15 mmol for the formic acid or ammonium formate, didn't look closely, and then 15 mmol of the catalyst.

Could you explain why they used 3.00 mmol, when they just used 15 mmol for another reagent, and not 15.00?
 

The_Real_Gus_Fring

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A Brief Review: Advancement in the Synthesis of Amine through the Leuckart Reactionby Qasim Umar and Mei Luo

There you go, massive increases in yield and also speed.
41DxflatlineI don't understand any of the shit in that paper, please break it down. Also how high is the yield with this, what chemicals need to be used and how fast does this speed shit up? If possible just make a diagram plz.
 

jackofspades

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The leuckart is so simple, but the yields are absolutely garbage.

If people could figure out how to increase yields, this would help the clandestine chemistry community so much.

Apparently magnesium chloride can be used as a catalyst, from what I've gathered online, maybe that will help yields a few percent points.
CryoThioI don't have the link on hand, but I have read amongst the Rhodium archives that the use of a Dean Stark trap filled with water increased yeild. By removing water as it was generated but keeping the trap full gave a bette result.
 

Win Win

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The reactions proceed according to Scheme 1

Reagents and materials:

  • 1-Phenyl-2-propanone (P2P) 5.4 ml;
  • N-methylformamide 13.4 ml;
  • Sodium sulphate (Na2SO4);
  • Hydrochloric acid (14% aq HCl) 32.1 ml or 20 ml 44% sulfuric acid H2SO4;
  • DCM 100-150 ml;
  • Sodium hydroxide (NaOH) 9,6 g in 24 ml H2O;
  • Sodium hydroxide (NaOH) 7.5 g in 30 ml H2O;
  • Ethanol 88% 10-15 ml;
  • Distilled water 100 ml;
  • Diethyl ether 5-10 ml;
  • Acetone 5-10 ml;
  • Hydrogen chloride gas (HCl);
  • Flasks;
  • Beakers;
  • Reflux condenser;
  • Hydrogen chloride gas generator;
  • Heater;

Execution of synthesis

N-methylformamide is added to P2P, a reflux condenser is attached. The mixture is heated to 165-170°C and refluxed at this temperature for 36 hours.

The initial components are N-methylformamide and P2P. Fig 1


Mixture of N-methylformamide and P2P. Fig 2

The reaction mass reaches a temperature of 160°C. Fig 3

The reaction mass after 1 hour of heating at the specified temperature. Fig 4

The reaction mass, after 18 hours of heating at the specified temperature, turns red. Fig 5

After 36 hours, the reaction mixture is cooled to room temperature. Then, 9.6 grams of sodium hydroxide dissolved in 24 ml of water is added, and the reaction mixture is refluxed for 2 hours with vigorous stirring. There is a significant release of methylamine or ammonia, even upon loading 5 grams!!! Fig 6

After 2 hours of boiling, the reaction mixture is cooled to room temperature and separated into different layers. Fig 7

An aqueous layer is discarded. Hydrochloric acid 32.1 ml (14% aq HCl) or 20 ml 44% sulfuric acid H2SO4 is added to a red organic layer. Fig 8

The mixture is boiled under a reflux condenser for 2 hours. After boiling, the color changes to dark green when treated with hydrochloric acid, while it remains brown when treated with sulfuric acid. Fig 9

Then, the solution is cooled to room temperature. The desired aqueous layer is separated, and the organic layer is further washed with water. NaOH solution (7.5 g in water 30 ml) is added. After the addition of the alkali, the color turns brown again. Fig 10

Methamphetamine is extracted from the aqueous layer with several portions of DCM. Fig 11

The DCM layer is dried with anhydrous sodium sulfate and filtered through a paper filter. Fig 12

DCM is distilled off at a temperature of 90°C. Fig 13

In the flask, there remains a brown oil of the free base with a characteristic amine odor. Fig 14

The obtained free base is dissolved in ethanol and saturated with hydrogen chloride until a strongly acidic reaction is achieved. The color of the solution should also change to raspberry. Fig 15

The resulting solution is evaporated to crystallization. Ultimately, a brown mass is obtained. Fig 16

Subsequently, the mass is fully crystallized. Fig 17

To the obtained crystallized mass, a small volume of diethyl ether is added, and it is transferred to a porous filter. Only one diethyl ether washing doesn't yield a pure product. Fig 18

Further washing with even strongly cooled acetone does not yield an absolutely pure product and leads to significant losses due to its high solubility. Fig 19
The final powdery product is the hydrochloride methamphetamine salt. Fig 20

Due to the fact that the final product is heavily contaminated, despite using initially purified P2P, an analyzing of the obtained data recommends (especially for larger loading volumes of 50 g P2P and more) mandatory steam distillation of the obtained methamphetamine free base after DCM extraction. This will help to avoid significant additional losses. Additionally, based on the conducted experiments, it should be noted that hydrolysis with sulfuric acid is more convenient and prevents its volatilization during boiling, unlike hydrochloric acid.

The yield of the hydrochloride (hydrolysis with hydrochloric acid) after washing with diethyl ether and acetone is 2.3 g or 30.8%.
The yield of the hydrochloride (hydrolysis with sulfuric acid) after washing with diethyl ether and acetone is 2.4 g or 32.1%.
When using steam distillation of the free base after the removal of DCM, the yield of the free base is 2.3-2.4 g or 38.3-40%.

Subsequent yield of the hydrochloride is 2.7-2.8 g or 36.2-37.5%.
GhostChemistMay i know your fig 9 boild under reflux condesor for 2 hour. What is the temperature?
 

Win Win

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The reactions proceed according to Scheme 1

Reagents and materials:

  • 1-Phenyl-2-propanone (P2P) 5.4 ml;
  • N-methylformamide 13.4 ml;
  • Sodium sulphate (Na2SO4);
  • Hydrochloric acid (14% aq HCl) 32.1 ml or 20 ml 44% sulfuric acid H2SO4;
  • DCM 100-150 ml;
  • Sodium hydroxide (NaOH) 9,6 g in 24 ml H2O;
  • Sodium hydroxide (NaOH) 7.5 g in 30 ml H2O;
  • Ethanol 88% 10-15 ml;
  • Distilled water 100 ml;
  • Diethyl ether 5-10 ml;
  • Acetone 5-10 ml;
  • Hydrogen chloride gas (HCl);
  • Flasks;
  • Beakers;
  • Reflux condenser;
  • Hydrogen chloride gas generator;
  • Heater;

Execution of synthesis

N-methylformamide is added to P2P, a reflux condenser is attached. The mixture is heated to 165-170°C and refluxed at this temperature for 36 hours.

The initial components are N-methylformamide and P2P. Fig 1


Mixture of N-methylformamide and P2P. Fig 2

The reaction mass reaches a temperature of 160°C. Fig 3

The reaction mass after 1 hour of heating at the specified temperature. Fig 4

The reaction mass, after 18 hours of heating at the specified temperature, turns red. Fig 5

After 36 hours, the reaction mixture is cooled to room temperature. Then, 9.6 grams of sodium hydroxide dissolved in 24 ml of water is added, and the reaction mixture is refluxed for 2 hours with vigorous stirring. There is a significant release of methylamine or ammonia, even upon loading 5 grams!!! Fig 6

After 2 hours of boiling, the reaction mixture is cooled to room temperature and separated into different layers. Fig 7

An aqueous layer is discarded. Hydrochloric acid 32.1 ml (14% aq HCl) or 20 ml 44% sulfuric acid H2SO4 is added to a red organic layer. Fig 8

The mixture is boiled under a reflux condenser for 2 hours. After boiling, the color changes to dark green when treated with hydrochloric acid, while it remains brown when treated with sulfuric acid. Fig 9

Then, the solution is cooled to room temperature. The desired aqueous layer is separated, and the organic layer is further washed with water. NaOH solution (7.5 g in water 30 ml) is added. After the addition of the alkali, the color turns brown again. Fig 10

Methamphetamine is extracted from the aqueous layer with several portions of DCM. Fig 11

The DCM layer is dried with anhydrous sodium sulfate and filtered through a paper filter. Fig 12

DCM is distilled off at a temperature of 90°C. Fig 13

In the flask, there remains a brown oil of the free base with a characteristic amine odor. Fig 14

The obtained free base is dissolved in ethanol and saturated with hydrogen chloride until a strongly acidic reaction is achieved. The color of the solution should also change to raspberry. Fig 15

The resulting solution is evaporated to crystallization. Ultimately, a brown mass is obtained. Fig 16

Subsequently, the mass is fully crystallized. Fig 17

To the obtained crystallized mass, a small volume of diethyl ether is added, and it is transferred to a porous filter. Only one diethyl ether washing doesn't yield a pure product. Fig 18

Further washing with even strongly cooled acetone does not yield an absolutely pure product and leads to significant losses due to its high solubility. Fig 19
The final powdery product is the hydrochloride methamphetamine salt. Fig 20

Due to the fact that the final product is heavily contaminated, despite using initially purified P2P, an analyzing of the obtained data recommends (especially for larger loading volumes of 50 g P2P and more) mandatory steam distillation of the obtained methamphetamine free base after DCM extraction. This will help to avoid significant additional losses. Additionally, based on the conducted experiments, it should be noted that hydrolysis with sulfuric acid is more convenient and prevents its volatilization during boiling, unlike hydrochloric acid.

The yield of the hydrochloride (hydrolysis with hydrochloric acid) after washing with diethyl ether and acetone is 2.3 g or 30.8%.
The yield of the hydrochloride (hydrolysis with sulfuric acid) after washing with diethyl ether and acetone is 2.4 g or 32.1%.
When using steam distillation of the free base after the removal of DCM, the yield of the free base is 2.3-2.4 g or 38.3-40%.

Subsequent yield of the hydrochloride is 2.7-2.8 g or 36.2-37.5%.
GhostChemistHi sir. I cant get N-methylformamide. Got other material can replace N-methylformamide?
 

CryoThio

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Hi sir. I cant get N-methylformamide. Got other material can replace N-methylformamide?
Win WinNot the person you asked, but I've found a possible workaround, if you can find the chemical.

N methylacetamide. You can't just substitute it out, you have to hydrolyse the NMeAcet to produce acetic acid and methylamine, isolate the methylamine, react it with formic acid, heat it, then you have NMF.

You can use methyalmine and formic acid together as a substitute for NMF, as the methylammonium salts or the amide works.
 
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Not the person you asked, but I've found a possible workaround, if you can find the chemical.

N methylacetamide. You can't just substitute it out, you have to hydrolyse the NMeAcet to produce acetic acid and methylamine, isolate the methylamine, react it with formic acid, heat it, then you have NMF.

You can use methyalmine and formic acid together as a substitute for NMF, as the methylammonium salts or the amide works.
CryoThioIn my place i can get methylamine solution and methylammonium salts. What is NMF?
 

Win Win

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What is the ratio?
 

Jesse_Pinkman_

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Win Win

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Did you read the beginning of this thread? Please do it carefully, everything is written there.
Jesse_Pinkman_Yes sir i have read all… but i still cant understand use what material to replace N methylacetamide. Maybe i am urgent to learn it… cuz i have 20 little p2p
 

CryoThio

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Yes sir i have read all… but i still cant understand use what material to replace N methylacetamide. Maybe i am urgent to learn it… cuz i have 20 little p2p
Win WinIf you have access to methyl ammonium salts, aka methylamine formate, you don't need anything else really. You are good to go.
 

CryoThio

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situ1984That's methylammonium chloride.

It can be used in this case, but not directly.

You'd need to remove the chloride by using an alkali base, then I believe use this solution in the reaction vessel, or throw in some formic acid and heat until all water is removed, then use the created n methyl formamide in the reaction.

Methylammonium formate works, or n methyl formamide, but not methylamine hydrochloride, which is what you posted.
 

situ1984

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That's methylammonium chloride.

It can be used in this case, but not directly.

You'd need to remove the chloride by using an alkali base, then I believe use this solution in the reaction vessel, or throw in some formic acid and heat until all water is removed, then use the created n methyl formamide in the reaction.

Methylammonium formate works, or n methyl formamide, but not methylamine hydrochloride, which is what you posted.
CryoThioThank you, this is very useful to me. Can you help me make another detailed process for hydroiodic acid and ephedrine? I want to start simple.
 
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