Research on the Use of Pure and Impure P2P in the Production of Amphetamine and Methamphetamine

[GhostChemist]

Reactions proceed according to Scheme 1.

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​

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​

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​

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.
​

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.​

Conclusions

1. 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.​
2. 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".​
3. 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.​
4. 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.​

 

[the money]

You are really amazing, you always surprise us with your experiences

 

[lalosalamanca84]

Do you can ise this method f
do you think this method can be used for 100x more production of amphetamine? that with pure p2p we get about 600 ml of pure amp. free base ?

 

[UWe9o12jkied91d]

Yes, at least from what I can remember, I read it's used in mexico on a large scale, there is literature that mentions this

 

[the money]

Yes

 

[Mr.Blanks00]

hello Mr. ghost chemist, can you make the crystallization, and how big is the size of the crystal needle, and can you test it by burning it so you can see if it leaves a mark or not on a glass plate.

 

[G.Patton]

There is video how to get d-meth crystals, look at there

 

[hy16a]

Where is it?

 

[OrgUnikum]

You forgot the methylamine in the first reaction drawing, very fist picture

What is the difference between "pure" and "impure" P2P? In the pictures it looks pretty much the same and not at all like P2P is supposed to look like. What would be a clear, highly refractive thin oil which is clear or has a very slight yellow tint. Her both are dark brown.

And sorry, nobody gets over 40% Amphetamine from an Al/Hg with Ammonia, I told the reason for this already elsewhere, it is the problem of formation of di-alkyl-amphetamine instead of Amphetamine. Reason: The Amphetamine as primary Amine is a much stronger nucleophile then Ammonia. At least 20 times as strong. Therefore the remaining P2P is much more probable to rect with the Amphetamine then with Ammonia what ends up with mostly di-alkyl-Amphetamine what is two P2P molecules having formed one big molecule with one Amino group. Thats why all attempts to aminate P2P with Ammonia give lousy to zero Amphetamine. Reactions which work are those which form some intermediate like formylamphetamine in the Leuckart which prevent the attack of P2P on the freshly formed Amine.

Here is an excerpt from the attached article which shows what one gets, funny is that the authors did not comprehend what the actual problem is and blamed it lamely on solubility. Shows nicely how rare really good chemists are.

 

[GhostChemist]

Hi! Thanks, Scheme 1 is corrected.
Nucleophilic properties are also an important parameter, but ammonia is a very volatile reagent that is ligter than air. Therefore, during the local heating on amalgam centers, evaporation will occur of ammonia.

 

[OrgUnikum]

As bonus I got a forensic article from Kangaroo Country where they do the Leuckart in different variations with pure and impure (30%) P2P and they have some interesting results as can be seen in table I and table II of the article.

 

[GhostChemist]

It`s an interesting study, but even in the tables, the experiments were not identically. For example, in experiment where Ammonium carbonate 5 eq + Formic acid 5 eq, the reaction time is 8 h, while in another experiment it`s 14 h.

 

[OrgUnikum]

They are putting up the best results they achieved with certain reagents, or thats how it is done in scientific literature to avoid the complete cluttering of articles which useless data.
Also it is an scientific article from Australia and worse it is a forensic article, the first tells there is a maybe 50% chance thats correct and the second tells that there is a 100% chance of some obfusication taking place. I mean, thats the enemy, yes?
Still there is a lot genuine information left to learn something from.
And do not forget thats Formylamphetamine they are talking about and they state not more then 37% Yield in a 2 hours acid hydrolysis with HCl, with a 82% product purity, whats lousy at best..

 

[41Dxflatline]

How about using an addition funnel to continue to add ammonia to the reaction?

 

[GhostChemist]

Simply adding ammonia is not sufficient, because the process is rapid. It`s possible that with excess pressure, the product yield may be increase.