Reactions proceed according to Scheme 1.
Prepared aluminum amalgam. Fig 2
Close-up view of properly amalgamated aluminum. Fig 2.1
Initial reagents for obtaining Amphetamine and Methamphetamine:
Aqueous ammonia solution, impure P2P, aqueous sodium chloride solution, ethanol for obtaining Amphetamine. Fig 3
Aqueous ammonia solution, pure P2P, aqueous sodium chloride solution, ethanol for obtaining Amphetamine. Fig 4
Aqueous ammonia solution, impure P2P, aqueous sodium chloride solution, ethanol for obtaining Methamphetamine. Fig 5
Aqueous ammonia solution, pure P2P, aqueous sodium chloride solution, ethanol for obtaining Methamphetamine. Fig 6
Progress of the reaction. Fig 8
End of the reaction. After that, a solution of sodium hydroxide is added to the reaction mixture to dissolve residual aluminum. Fig 9
The reaction mixture is maintained at room temperature for 30-40 minutes and then allowed to settle for sediment compaction. Fig 10
The solution is decanted and filtered, and the precipitate is additionally washed with ethanol to extract the formed amines.
Solution of amphetamine obtained from impure P2P. Fig 11
Solution of amphetamine obtained from pure P2P. Fig 12
Solution of methamphetamine obtained from impure P2P. Fig 13
Solution of methamphetamine obtained from pure P2P. Fig 14
Dried solution of amphetamine in dichloromethane, obtained from impure P2P. Fig 15
Dried solution of amphetamine in dichloromethane, obtained from pure P2P. Fig 16
Dried solution of methamphetamine in dichloromethane, obtained from impure P2P. Fig 17
Dried solution of methamphetamine in dichloromethane, obtained from pure P2P. Fig 18
Amphetamine in the free base form, obtained from impure P2P. Fig 19
Amphetamine in the free base form, obtained from pure P2P. Fig 20
Methamphetamine in the free base form, obtained from impure P2P. Fig 21
Methamphetamine in the free base form, obtained from pure P2P. Fig 22
Acidified solution of sulfuric acid for amphetamine, obtained from pure P2P. Fig 24
Saturated hydrochloric acid solution for Methamphetamine, obtained from impure P2P. Fig 25
Saturated hydrochloric acid solution for Methamphetamine, obtained from pure P2P. Fig 26
The obtained solutions are evaporated to crystallization.
Crystallization of amphetamine sulfate obtained from impure P2P. Fig 27
Crystallization of amphetamine sulfate obtained from pure P2P. Fig 28
Crystallization of Methamphetamine hydrochloride obtained from impure P2P. Fig 29
Crystallization of Methamphetamine hydrochloride obtained from pure P2P. Fig 30
Appearance of amphetamine sulfate obtained from impure P2P. Fig 31
Appearance of amphetamine sulfate obtained from pure P2P. Fig 32
Appearance of Methamphetamine hydrochloride obtained from impure P2P. Fig 33
Appearance of Methamphetamine hydrochloride obtained from pure P2P. Fig 34
Conclusions
Reagents and materials for a single synthesis.
For Methamphetamine
- Aluminum foil 14 µm, 10.5 g
- Mercury(II) chloride, 0.1 g
- Distilled water, 3 L
- 10 g of pure or impure P2P (P2P obtained through the reduction of P2NP with sodium borohydride)
- Methylamine 39%, 25-30 ml
- Sodium chloride, 10 g in 30 ml of water
- Ethanol or IPA, 150 ml
- Dichloromethane (DCM), 150-200 ml
- Ethanol 88%, 25 ml
- Ammonium chloride, 50-100 g
- Concentrated sulfuric acid 80%, 15-20 ml
- Technical water, 2 L with 500 g of ice
- Anhydrous sodium sulfate, 20-30 g
- 10-15 ml of 25% NaOH
- Diethyl ether, 15 ml
- Acetone, 20-25 ml
- 2 L flask, 500 ml flask, 250 ml flask
- 3-necked 500 ml flask for generating hydrogen chloride
- Reflux condenser
- Apparatus for solvent distillation with a water bath
- Vacuum filtration setup
- Separatory funnel
- Silicone grease for joints
- Filter paper
- Funnels
- Beakers
- Heater
For Amphetamine
- 10.5 g of 14 µm aluminum foil
- 0.1 g of mercury chloride
- 50 ml of 20-25% ammonia
- 10 g of pure or impure P2P (P2P obtained through the reduction of P2NP with sodium borohydride)
- 100-150 ml of 88% ethanol or isopropyl alcohol
- 150-200 ml of dichloromethane (DCM)
- Concentrated sulfuric acid 80%, 3-5 ml
- pH indicator paper
- Technical water, 2 L with 500 g of ice
- Anhydrous sodium sulfate, 20-30 g
- 10-15 ml of 25% NaOH
- Acetone, 35-40 ml
- 2 L flask, 500 ml flask, 250 ml flask
- Reflux condenser
- Apparatus for solvent distillation with a water bath
- Vacuum filtration setup
- Separatory funnel
- Silicone grease for joints
- Filter paper
- Funnels
- Beakers
- Heater
In this study, a series of 4 syntheses of Methamphetamine hydrochloride and amphetamine sulfate were conducted using pure and impure P2P by the amalgamation method. P2P was obtained via the reduction of P2NP using a borohydride method.
The preparation of aluminum amalgam was the same in all 4 experiments and involved adding a portion of mercury(II) chloride to aluminum foil submerged in water. After the disappearance of shine on the foil and the intense evolution of hydrogen (approximately after 10-15 minutes), the solution was decanted, and the amalgam was washed with two portions of water.
Aluminum before amalgamation. Fig 1
The preparation of aluminum amalgam was the same in all 4 experiments and involved adding a portion of mercury(II) chloride to aluminum foil submerged in water. After the disappearance of shine on the foil and the intense evolution of hydrogen (approximately after 10-15 minutes), the solution was decanted, and the amalgam was washed with two portions of water.
Aluminum before amalgamation. Fig 1
Prepared aluminum amalgam. Fig 2
Close-up view of properly amalgamated aluminum. Fig 2.1
Initial reagents for obtaining Amphetamine and Methamphetamine:
Aqueous ammonia solution, impure P2P, aqueous sodium chloride solution, ethanol for obtaining Amphetamine. Fig 3
Aqueous ammonia solution, pure P2P, aqueous sodium chloride solution, ethanol for obtaining Amphetamine. Fig 4
Aqueous ammonia solution, impure P2P, aqueous sodium chloride solution, ethanol for obtaining Methamphetamine. Fig 5
Aqueous ammonia solution, pure P2P, aqueous sodium chloride solution, ethanol for obtaining Methamphetamine. Fig 6
Preparation of ice-cold water in advance is necessary for cooling the flask. All components are added to the amalgam, and a reflux condenser is attached. It should be noted that in the case of amphetamine, with impure P2P, the heating starts relatively quickly, so cooling is required immediately and more frequently (3-5 times) throughout the reaction. In the case of purified P2P for obtaining amphetamine and methamphetamine, the reaction proceeds more smoothly, with the flask requiring cooling only 1-2 times during the entire process. The entire process takes 30-40 minutes for amphetamine and 2.5-3 hours for Methamphetamine.
The reaction starts after loading all the components. Fig 7
The reaction starts after loading all the components. Fig 7
Progress of the reaction. Fig 8
End of the reaction. After that, a solution of sodium hydroxide is added to the reaction mixture to dissolve residual aluminum. Fig 9
The reaction mixture is maintained at room temperature for 30-40 minutes and then allowed to settle for sediment compaction. Fig 10
The solution is decanted and filtered, and the precipitate is additionally washed with ethanol to extract the formed amines.
Solution of amphetamine obtained from impure P2P. Fig 11
Solution of amphetamine obtained from pure P2P. Fig 12
Solution of methamphetamine obtained from impure P2P. Fig 13
Solution of methamphetamine obtained from pure P2P. Fig 14
To the obtained solution, portions of dichloromethane are added, and the mixture is vigorously shaken for complete extraction of amines. After phase separation, dichloromethane is separated in a separatory funnel and dried with anhydrous sodium sulfate.
Dried solution of amphetamine in dichloromethane, obtained from impure P2P. Fig 15
Dried solution of amphetamine in dichloromethane, obtained from pure P2P. Fig 16
Dried solution of methamphetamine in dichloromethane, obtained from impure P2P. Fig 17
Dried solution of methamphetamine in dichloromethane, obtained from pure P2P. Fig 18
The solutions in DCM are completely evaporated to a temperature of 90°C, resulting in the formation of an oil with distinct odors different from ammonia and methylamine. Vacuum distillation can also be used. Acetone is added to the obtained free bases.
Amphetamine in the free base form, obtained from impure P2P. Fig 19
Amphetamine in the free base form, obtained from pure P2P. Fig 20
Methamphetamine in the free base form, obtained from impure P2P. Fig 21
Methamphetamine in the free base form, obtained from pure P2P. Fig 22
To amphetamine, a small amount of acetone and concentrated sulfuric acid are added until the pH reaches 5.5-6.
To Methamphetamine, a small amount of acetone is added, and gaseous hydrogen chloride is passed through until saturation and a change in color to intense pink.
Acidified solution of sulfuric acid for amphetamine, obtained from impure P2P. Fig 23
To Methamphetamine, a small amount of acetone is added, and gaseous hydrogen chloride is passed through until saturation and a change in color to intense pink.
Acidified solution of sulfuric acid for amphetamine, obtained from impure P2P. Fig 23
Acidified solution of sulfuric acid for amphetamine, obtained from pure P2P. Fig 24
Saturated hydrochloric acid solution for Methamphetamine, obtained from impure P2P. Fig 25
Saturated hydrochloric acid solution for Methamphetamine, obtained from pure P2P. Fig 26
The obtained solutions are evaporated to crystallization.
Crystallization of amphetamine sulfate obtained from impure P2P. Fig 27
Crystallization of amphetamine sulfate obtained from pure P2P. Fig 28
Crystallization of Methamphetamine hydrochloride obtained from impure P2P. Fig 29
Crystallization of Methamphetamine hydrochloride obtained from pure P2P. Fig 30
The crystallized mass of amphetamine sulfate is washed only with cold acetone. Methamphetamine hydrochloride is thoroughly washed first with a small portion of diethyl ether, and then with the volume of cold acetone until it becomes snow-white in color. The obtained salts are dried directly on a vacuum filter or under a stream of warm air.
Appearance of amphetamine sulfate obtained from impure P2P. Fig 31
Appearance of amphetamine sulfate obtained from pure P2P. Fig 32
Appearance of Methamphetamine hydrochloride obtained from impure P2P. Fig 33
Appearance of Methamphetamine hydrochloride obtained from pure P2P. Fig 34
Yield of amphetamine sulfate
From pure P2P, 5.65 g of amphetamine sulfate was obtained, which corresponds to 41.1% yield.
From impure P2P, 2.29 g of amphetamine sulfate was obtained, which corresponds to 16.68% yield.
From impure P2P, 2.29 g of amphetamine sulfate was obtained, which corresponds to 16.68% yield.
Yield of methamphetamine hydrochloride
From pure P2P, 9.6 g of methamphetamine hydrochloride was obtained, which corresponds to 69% yield.
From impure P2P, 5.05 g of methamphetamine hydrochloride was obtained, which corresponds to 36.5% yield.
From impure P2P, 5.05 g of methamphetamine hydrochloride was obtained, which corresponds to 36.5% yield.
Conclusions
- Analyzing the obtained data, it can be concluded that the synthesis of amphetamine sulfate from P2P through amalgamation is not advisable due to the fact that ammonia evaporates from the reaction volume under the influence of exothermic effects.
- The reduction in yields of amine salts by 2-2.5 times is due to impurities present in impure P2P, which intensify the exothermic effects and consequently increase the temperature, sometimes locally (localized overheating). This likely leads to thermal degradation of the desired product as well as evaporation of the starting methylamine and ammonia. Ammonia, being lighter than air, evaporates from the reaction volume much more easily than methylamine, which is heavier than air and remains in the reaction volume as a "cushion".
- The use of pure P2P allows for decent yields of amines and smoother progression of the exothermic process compared to the use of impure P2P.
- Overall, it is more advisable and cost-effective to use P2P, with prior purification, specifically for the synthesis of methamphetamine. Methamphetamine hydrochloride is much more stable during storage compared to amphetamine sulfate.
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