Amphetamine Synthesis via P2P Oxime Reduction

[alterego]

Hi there, great write up!
So manny respect for u guys bringing this up/ take time to share with us!
But 1 thing strugles me.
This forum teached me that Amfetamine should be white, other colors are (faulty) synthesis related,precursor/ poison leftovers...
I know its common to have a slight color change in the end product, but your end product is just full yellow/orange color ?
Whats the deal about that ?

 

[GhostChemist]

Hi there, great write up!
So manny respect for u guys bringing this up/ take time to share with us!
But 1 thing strugles me.
This forum teached me that Amfetamine should be white, other colors are (faulty) synthesis related,precursor/ poison leftovers...
I know its common to have a slight color change in the end product, but your end product is just full yellow/orange color ?
Whats the deal about that ?

alteregoHi, alterego!
Yep, that the fact pure Amfetamine have a white color.
The yellow color of Amfetamine is specifically due to its oxidation.
For example, during the evaporation of the solvent at its boiling and during storage with exposure to air.
Additionally, the yellow color can be attributed to impurities of iron salts and sodium sulphate.
In future research, we will study this further and publish new research data.

 

[OrgUnikum]

is the purity affected at all by long term storage?

mithyl2It will hold a long time if it is dry, pure, kept cool, away from light and air. Nevertheless there was an article where they examined stored drugs from an old pharmacy which were in a dark cool place for 30 years + and one of the meds was Amphetamine. It had deteriorated to less then half the original amount Amphetamine present over this long time.
Primary Amines are just very reactive even as salts. Amphetamine base deteriorates within hours when subjected to sunlight and 25 °C + in the presence of oxygen (like a bottle with air above the liquid). Best make the salt instantly or keep in a deep-freezer.

 

[Win Win]

Hello! I have 20 liters of p2p, but I can't find a best recipe to experiment with. Is this the best recipe?

 

[GhostChemist]

Hello! I have 20 liters of p2p, but I can't find a best recipe to experiment with. Is this the best recipe?

Win WinHi!

What do you plan to obtain from p2p? Amphetamine or Methamphetamine?

 

[door]

I recomended using the method with NaBH4. Spoiler: a video of this method will be available soon.
You also need to obtain a methylamine solution in alcohol (methanol or IPA) from methylamine hydrochloride. Can you do this stage?
http://bbzzzsvqcrqtki6umym6itiixfhn...e-methylamine-gas-to-methanol.1315/#post-4279

GhostChemistWhen will video method be can you let me know please bozz

 

[Win Win]

Yes i can

 

[GhostChemist]

Yes i can

Win WinIn the next step I recomended carried out a trial synthesis of meth for your experimental expirience.
How many g of P2P you willing to trial synthesis?
P2P should be pure (steam distillation will be applied).
You will need of drying agents such as SiO2 (silica gel) and angydrous Na2SO4 (sodium sulphate). Do You have this compounds?
Main reaction carry out in three-necked flask with stirrer and thermometr in ice batch.

 

[GhostChemist]

Yes i can

Win WinFirst stage: Drying reagents, Imine preparation and Reduction.
Proportions for 10 g of pure P2P (after distillation add SiO2):
1,1 g NaBH4 powder
20 ml of 40% methylamine in methanol (methanol saturated of methylamine) or 23-25 ml of 30% methylamine in IPA
20-50 g or more SiO2
20-30 g or more Na2SO4 angydrous
65-80 ml absolute MeOH or IPA (isopropyl alcohol)
ice bath
ice reserves for a few days
thermometere with range -20 to +50C preferably
Preparing these reagents and flasks for start test working. Need a separate flask with germetic cork for drying of mixture p2p with absolute MeOH or IPA.
Are You understand it?

 

[Win Win]

First stage: Drying reagents, Imine preparation and Reduction.
Proportions for 10 g of pure P2P (after distillation add SiO2):
1,1 g NaBH4 powder
20 ml of 40% methylamine in methanol (methanol saturated of methylamine) or 23-25 ml of 30% methylamine in IPA
20-50 g or more SiO2
20-30 g or more Na2SO4 angydrous
65-80 ml absolute MeOH or IPA (isopropyl alcohol)
ice bath
ice reserves for a few days
thermometere with range -20 to +50C preferably
Preparing these reagents and flasks for start test working. Need a separate flask with germetic cork for drying of mixture p2p with absolute MeOH or IPA.
Are You understand it?

GhostChemistYes i understood

 

[Win Win]

I have 1set 1L double jacket reactor. And 1set 10L double jacket reactor. 1set 10L vaporrator. Na2SO4 i got. SiO2 can get it.

 

[GhostChemist]

I have 1set 1L double jacket reactor. And 1set 10L double jacket reactor. 1set 10L vaporrator. Na2SO4 i got. SiO2 can get it.

Win WinSiO2 needs be purchased. It is a good absorbent in synthesis.
This stage drying methylamine in MeOH or IPA, cooling is not necessary.
Carry out the process in a separate flask or bottle (polypropylene or glass) with germetic cork.
In this flask add 20-30 g Na2SO4 angydrous + 20 g SiO2, next add 20-25 ml of 30-40% methylamine in alcohol and 65 ml absolute MeOH or IPA (isopropyl alcohol). Close hermetic cork and drying 1-2 days, sometimes shaking.

Stage preparing of imine. The main reactor will be equipped with termometr, ice bath and a stirrer. The reactor should be connected with atmosphere through SiO2 ( See attached scheme).
In main reactor place 30 g SiO2 or more, but volume of SiO2 less than liquid. Drying reactor at 1 h. After that, adding methylamine solution after drying from separate flask. Methylamine solution is added to the reactor carefully draining it from the Na2SO4+ SiO2. The Na2SO4+ SiO2 is washed with several portions of IPA.
After that in the main reacor adding p2p. Reaction mass (RM) stirring at 2h.

Stage reduction. Cool the RM at 0-5C. Next adding very small portions of NaBH4. The temperature of RM not more than +15C!!! After added all NaBH4, RM stirring 1-1,5 days.

After 1-1,5 days in RM add distill water to dissolving precipitate. Decanted from SiO2. The SiO2 is washed with several portions of water. SiO2 is discarded. In this water solution RM add water solution of NaOH (10-15 g in 50 ml H2O). Next stages are classical extraction of DCM, Evaporation DCM and Saturation HCL of meth free base to hydrochloride.

 

[Win Win]

SiO2 needs be purchased. It is a good absorbent in synthesis.
This stage drying methylamine in MeOH or IPA, cooling is not necessary.
Carry out the process in a separate flask or bottle (polypropylene or glass) with germetic cork.
In this flask add 20-30 g Na2SO4 angydrous + 20 g SiO2, next add 20-25 ml of 30-40% methylamine in alcohol and 65 ml absolute MeOH or IPA (isopropyl alcohol). Close hermetic cork and drying 1-2 days, sometimes shaking.

Stage preparing of imine. The main reactor will be equipped with termometr, ice bath and a stirrer. The reactor should be connected with atmosphere through SiO2 ( See attached scheme).
In main reactor place 30 g SiO2 or more, but volume of SiO2 less than liquid. Drying reactor at 1 h. After that, adding methylamine solution after drying from separate flask. Methylamine solution is added to the reactor carefully draining it from the Na2SO4+ SiO2. The Na2SO4+ SiO2 is washed with several portions of IPA.
After that in the main reacor adding p2p. Reaction mass (RM) stirring at 2h.

Stage reduction. Cool the RM at 0-5C. Next adding very small portions of NaBH4. The temperature of RM not more than +15C!!! After added all NaBH4, RM stirring 1-1,5 days.

After 1-1,5 days in RM add distill water to dissolving precipitate. Decanted from SiO2. The SiO2 is washed with several portions of water. SiO2 is discarded. In this water solution RM add water solution of NaOH (10-15 g in 50 ml H2O). Next stages are classical extraction of DCM, Evaporation DCM and Saturation HCL of meth free base to hydrochloride.

View attachment 23757

GhostChemistWooo very clear… thank you sir. Once i start i will take photo part to part and show you.

 

[Win Win]

SiO2 needs be purchased. It is a good absorbent in synthesis.
This stage drying methylamine in MeOH or IPA, cooling is not necessary.
Carry out the process in a separate flask or bottle (polypropylene or glass) with germetic cork.
In this flask add 20-30 g Na2SO4 angydrous + 20 g SiO2, next add 20-25 ml of 30-40% methylamine in alcohol and 65 ml absolute MeOH or IPA (isopropyl alcohol). Close hermetic cork and drying 1-2 days, sometimes shaking.

Stage preparing of imine. The main reactor will be equipped with termometr, ice bath and a stirrer. The reactor should be connected with atmosphere through SiO2 ( See attached scheme).
In main reactor place 30 g SiO2 or more, but volume of SiO2 less than liquid. Drying reactor at 1 h. After that, adding methylamine solution after drying from separate flask. Methylamine solution is added to the reactor carefully draining it from the Na2SO4+ SiO2. The Na2SO4+ SiO2 is washed with several portions of IPA.
After that in the main reacor adding p2p. Reaction mass (RM) stirring at 2h.

Stage reduction. Cool the RM at 0-5C. Next adding very small portions of NaBH4. The temperature of RM not more than +15C!!! After added all NaBH4, RM stirring 1-1,5 days.

After 1-1,5 days in RM add distill water to dissolving precipitate. Decanted from SiO2. The SiO2 is washed with several portions of water. SiO2 is discarded. In this water solution RM add water solution of NaOH (10-15 g in 50 ml H2O). Next stages are classical extraction of DCM, Evaporation DCM and Saturation HCL of meth free base to hydrochloride.

View attachment 23757

GhostChemistSir after evaporate. Need use HCL gas to get crystall or just dropwise HCL untill ph6 to get crystall?
Thank you

 

[Win Win]

SiO2 needs be purchased. It is a good absorbent in synthesis.
This stage drying methylamine in MeOH or IPA, cooling is not necessary.
Carry out the process in a separate flask or bottle (polypropylene or glass) with germetic cork.
In this flask add 20-30 g Na2SO4 angydrous + 20 g SiO2, next add 20-25 ml of 30-40% methylamine in alcohol and 65 ml absolute MeOH or IPA (isopropyl alcohol). Close hermetic cork and drying 1-2 days, sometimes shaking.

Stage preparing of imine. The main reactor will be equipped with termometr, ice bath and a stirrer. The reactor should be connected with atmosphere through SiO2 ( See attached scheme).
In main reactor place 30 g SiO2 or more, but volume of SiO2 less than liquid. Drying reactor at 1 h. After that, adding methylamine solution after drying from separate flask. Methylamine solution is added to the reactor carefully draining it from the Na2SO4+ SiO2. The Na2SO4+ SiO2 is washed with several portions of IPA.
After that in the main reacor adding p2p. Reaction mass (RM) stirring at 2h.

Stage reduction. Cool the RM at 0-5C. Next adding very small portions of NaBH4. The temperature of RM not more than +15C!!! After added all NaBH4, RM stirring 1-1,5 days.

After 1-1,5 days in RM add distill water to dissolving precipitate. Decanted from SiO2. The SiO2 is washed with several portions of water. SiO2 is discarded. In this water solution RM add water solution of NaOH (10-15 g in 50 ml H2O). Next stages are classical extraction of DCM, Evaporation DCM and Saturation HCL of meth free base to hydrochloride.

View attachment 23757

GhostChemistSir What is the ratio of H2O and DCM?

 

[GhostChemist]

Sir What is the ratio of H2O and DCM?

Win WinBetter use HCL gas, and you can use dry ethylacetate as a solvent for dissolve free base of meth.
ratio of H2O and DCM: volume of H2O is approx to disolve precepitate. 250-300 ml DCM in 3-4 portions (for 10 g starting P2P) is give better and full extraction.

 

[Win Win]

SiO2 needs be purchased. It is a good absorbent in synthesis.
This stage drying methylamine in MeOH or IPA, cooling is not necessary.
Carry out the process in a separate flask or bottle (polypropylene or glass) with germetic cork.
In this flask add 20-30 g Na2SO4 angydrous + 20 g SiO2, next add 20-25 ml of 30-40% methylamine in alcohol and 65 ml absolute MeOH or IPA (isopropyl alcohol). Close hermetic cork and drying 1-2 days, sometimes shaking.

Stage preparing of imine. The main reactor will be equipped with termometr, ice bath and a stirrer. The reactor should be connected with atmosphere through SiO2 ( See attached scheme).
In main reactor place 30 g SiO2 or more, but volume of SiO2 less than liquid. Drying reactor at 1 h. After that, adding methylamine solution after drying from separate flask. Methylamine solution is added to the reactor carefully draining it from the Na2SO4+ SiO2. The Na2SO4+ SiO2 is washed with several portions of IPA.
After that in the main reacor adding p2p. Reaction mass (RM) stirring at 2h.

Stage reduction. Cool the RM at 0-5C. Next adding very small portions of NaBH4. The temperature of RM not more than +15C!!! After added all NaBH4, RM stirring 1-1,5 days.

After 1-1,5 days in RM add distill water to dissolving precipitate. Decanted from SiO2. The SiO2 is washed with several portions of water. SiO2 is discarded. In this water solution RM add water solution of NaOH (10-15 g in 50 ml H2O). Next stages are classical extraction of DCM, Evaporation DCM and Saturation HCL of meth free base to hydrochloride.

View attachment 23757

GhostChemistSir you give me this ratio is using how many little reactor?

 

[Win Win]

Better use HCL gas, and you can use dry ethylacetate as a solvent for dissolve free base of meth.
ratio of H2O and DCM: volume of H2O is approx to disolve precepitate. 250-300 ml DCM in 3-4 portions (for 10 g starting P2P) is give better and full extraction.

GhostChemistSir this is the first stage i follow your ratio to prepaid is it correct? All the solution become dry….

 

[eu.lab]

Very nice! Will try it

 

[Win Win]

First stage stirring RM at 1hour. The temperature is 0’c?

 

[GhostChemist]

First stage stirring RM at 1hour. The temperature is 0’c?

Win WinFirst stage. When added p2p to dry Methylamine, RM stirring 1-2 h at temperature range 0-5C
When addition NaBH4 (small portions!!!) temperature not more +15C! After added all NaBH4, RM stirring 1-1,5 days, temperature not more +20C (better +15C).

 

[OrgUnikum]

First stage. When added p2p to dry Methylamine, RM stirring 1-2 h at temperature range 0-5C
When addition NaBH4 (small portions!!!) temperature not more +15C! After added all NaBH4, RM stirring 1-1,5 days, temperature not more +20C (better +15C).

GhostChemistYou are doing this exceptionally well and I highly appreciate you are sharing your knowledge with others here.

It is a pity this is buried in the wrong thread, which is originally about Amphetamine synthesis from the Oxime not Meth by reductive Amination of P2P with Methylamine, but anyways, better here then not at all. I am happy that I have now posts I can point people to who are asking about this, so thx again!

 

[Win Win]

First stage my coolant circulation system set on 0c. Second stage all the way i set on 15c. Thank you

 

[OrgUnikum]

Reactions proceed according to Scheme 1

View attachment 21718 ​

Reagents and Materials:​

• 8.1 g of aluminum
• 0.05 g of mercury(II) chloride
• 5 g P2P
• 2 g of hydroxylamine or a mixture (50-60 ml of IPA (or ethanol) + 2.5 g of NaOH + 4.55 g of hydroxylamine hydrochloride)
• 50 ml of ethanol
• 2-liter flask
• 2 liters of ice-cold water (500 g of ice)
• 100 ml DCM
• 10 ml of acetone
• 1 ml of 89% sulfuric acid
• pH indicator paper
• Various-sized beakers
• Heater

Synthesis Procedure​

Starting materials for the synthesis. Fig 1

View attachment 21719​

In two separate beakers, hydroxylamine hydrochloride and sodium hydroxide are mixed with ethanol or IPA. Fig 2

View attachment 21720​

Next, the contents of the beakers are combined. Fig 3

View attachment 21721 ​

To the resulting mixture, P2P is added. The color changes from pale yellow to orange. Additionally, 50 ml of ethanol or IPA is added to the solution. Fig 4

View attachment 21722 ​

Next, aluminum amalgam is prepared using the standard method. Fig 5

View attachment 21723 ​

The prepared P2P oxime solution is added to the resulting aluminum amalgam, and a reflux condenser is connected. Fig 6​

View attachment 21724 ​

The reaction proceeds slowly without significant heat generation, and additional cooling is not required. It is possible that with larger loads, the exothermic effect would be more pronounced. Fig 7​

View attachment 21725​

The reaction is fully completed within 1-1.5 hours. Fig 8

View attachment 21726​

The reaction mass is filtered through a paper filter. Fig 9

View attachment 21727​

Due to the fine dispersion of the formed sediment, filtration is quite challenging. In this case, it is possible to perform the extraction of DСM from the reaction mixture directly with the sludge and then filter the organic extract. Fig 10​

View attachment 21728​

The filtered DСM is dried with anhydrous sodium sulfate. Fig 11

View attachment 21729​

DCM is distilled off at a temperature of 90°C. Fig 12

View attachment 21730​

After distillation, a yellow-colored oil remains in the residue. Fig 13

View attachment 21731​

The obtained oil is transferred to a beaker, and any remaining residues in the flask are rinsed with acetone. The pH of the amphetamine oil is alkaline. Fig 14

View attachment 21732​

Sulfuric acid is added to the obtained amphetamine solution until the pH reaches 5-6, resulting in the precipitation of amphetamine sulfate. Fig 15

View attachment 21733​

The obtained solution is evaporated to half of its volume, and then 5 mL of anhydrous cold acetone is added. The precipitate is filtered off and dried. Fig 16

View attachment 21734​

The yield of amphetamine sulfate is 2.5 g, which corresponds to 36%.​

GhostChemist
Good post, I want to make some qualified suggestions how yields can be improved:

- The Al/Hg should be done in acidic conditions similar to the Al/Hg P2NP reduction. Alternativly the reduction is done with di-ethyl ether or THF as solvent and only a measured amount of water. Some alcohol will not hurt much, so reduce the alcohol volume of the Oxime solution to a minimum and use as is with THF. No further addition of water is needed then.

- Oxime formation is a bitch and needs a big excess of Hydroxylamine added in several portions. Best results by now have been achieved by using a 5 g P2P to 5 g Hydroxylamine.HCL to 5 ml Pyridine in 50 ml methanol and nuking this to 115 °C in a microwave using a PTFE pressure vessel. Rapid cooling down in a ice-water bath, adding Pyridine/Hydroxylamine.HCl and nuke again repeat twice more. Thats still experimental, no guarantees whatsoever. I hope to be able to do this in a normal pressure vessel and immersion of this into a hot-oil bath or another way of rapid heating as thats what this is all about. Iron (salts) catalyze Hydroxylamine decomposition btw.

- Al/Hg workup is a mess, NaBH4/CuSO4 is probably the better way to do this reduction. (Done the same way as a P2NP reduction)

 

[rampage]

hi
whats the process of getting methylamine in methanol or ipa?
can you start with methylamine hcl?