One-pot Amphetamine Synthesis From P2NP With NaBH4/CuCl2 (1kg scale)

[G.Patton]

My question now: Can the mixture of NabH4 and P2NP be separated in any way so that both can be returned to their original forms? so that it can be used again for another new synthesis.

Sasha89Is your NaBH4 dissolved in IPA/H2O? In this case, answer - no. The better thing which you can do - put your mixture in fridge.

 

[Mystery_chemistry]

hi i found some old notes regarding this p2np reduction. photo attached

 

[Mystery_chemistry]

I also found a reduction with sodium or potassium borohydride without the use of copper chloride with only acetic acid.​

General Procedure​

Use the following amounts of reagents:

• 1 mole eq. of any arylnitrostyrene
• 1,25 mol eq. potassium or sodium borohydride1
• Approximately 5*wt. of the nitrostyrene in mL's of IPA (i.e. 10 g P2NP would require 50 mL IPA)
• 2/5 the vol of IPA used of dH2O

Mix the IPA and water in a sufficiently large beaker. Add the borohydride in one portion and commence stirring. Begin adding the nitrostyrene in small portions after a minute or two. This will cause a rise in temperature and moderate hydrogen evolution. Add the substrate in small portions to avoid any nasty volcano reactions. The rate of addition should be such that a lively evolution of hydrogen can be observed in the beaker, but slow enough to avoid the reaction shooting out of the flask.

Once all of the substrate has been added, keep stirring the mixture for 30 mins. The colour of the mixture should be alot more pale than that of the nitrostyrene2. Add dilute (32-80%) acetic acid drop wise untill fizzing stops. Add solid non-iodized table salt while stirring heavily, untill no more dissolves. Suction filter the mixture, to remove any remaining salt and borates. Rinse the filter cake with a little fresh IPA. The IPA layer, containing the product will float on top of the water. Isolate the IPA layer, and discard the water.

At this point the reaction is over, and the IPA layer contains a product which is sufficiently pure for a CTH, Zn/Formate, SnCl2 nitro reduction or whatever your preference might be. So simply use this IPA direcly.

 

[cesc]

I also found a reduction with sodium or potassium borohydride without the use of copper chloride with only acetic acid.​

General Procedure​

Use the following amounts of reagents:

• 1 mole eq. of any arylnitrostyrene
• 1,25 mol eq. potassium or sodium borohydride1
• Approximately 5*wt. of the nitrostyrene in mL's of IPA (i.e. 10 g P2NP would require 50 mL IPA)
• 2/5 the vol of IPA used of dH2O

Mix the IPA and water in a sufficiently large beaker. Add the borohydride in one portion and commence stirring. Begin adding the nitrostyrene in small portions after a minute or two. This will cause a rise in temperature and moderate hydrogen evolution. Add the substrate in small portions to avoid any nasty volcano reactions. The rate of addition should be such that a lively evolution of hydrogen can be observed in the beaker, but slow enough to avoid the reaction shooting out of the flask.

Once all of the substrate has been added, keep stirring the mixture for 30 mins. The colour of the mixture should be alot more pale than that of the nitrostyrene2. Add dilute (32-80%) acetic acid drop wise untill fizzing stops. Add solid non-iodized table salt while stirring heavily, untill no more dissolves. Suction filter the mixture, to remove any remaining salt and borates. Rinse the filter cake with a little fresh IPA. The IPA layer, containing the product will float on top of the water. Isolate the IPA layer, and discard the water.

At this point the reaction is over, and the IPA layer contains a product which is sufficiently pure for a CTH, Zn/Formate, SnCl2 nitro reduction or whatever your preference might be. So simply use this IPA direcly. View attachment 5315

Mystery_chemistryYes, there is only t'he first step, t'he second one is Hcl Sn , formic àcid Zinc, etc...to reach t'he amine.
In my way, with Zinc-hcl, somebody reach a pinky amine or Who knows..help!

 

[Mystery_chemistry]

Oh, and one more question about this IPA and water, is there too much of it? I read that on 1g p2np 5m IPA and 0.4 water: it would then come out 7l 5 IPA / 2 h2o

 

[G.Patton]

1g p2np 5m IPA and 0.4 water: it would then come out 7l 5 IPA / 2 h2o

Mystery_chemistrywhat does it mean, 5m IPA? 0.4 of water?? Whaaat? Man, you have to represent your minds in commonly understand language...

7l 5 IPA / 2 h2o

???

 

[Mystery_chemistry]

quickly spelled and escaped letters. I say that I read somewhere and they gave such proportions. to 5ml of IPA / 1g of P2NP and 0.4 times volume of H2O in RBF was dumped 6 mol eq. of NaBH4.

therefore, counting their proportions, 5000ml of IPA and 2000ml of water comes out…. and here in the recipe is 18l 2: 1 or 12l: 6l.

 

[btcboss2022]

Hello,

I did it in big scale for first time with professional equipment and littles changes and I had 1 liter of freebase of very good quality and clean for each kg of P2NP.
One of the best routes for that product.
Thanks.

 

[G.Patton]

Hello,

I did it in big scale for first time with professional equipment and littles changes and I had 1 liter of freebase of very good quality and clean for each kg of P2NP.
One of the best routes for that product.
Thanks.

btcboss2022Hi. Cool! What percentage of yield have you got?

 

[btcboss2022]

Hi. Cool! What percentage of yield have you got?

G.PattonHere are the exactly details how I did, I must did it in these amounts because I didn't had enough sodium borohydride( new order arriving ;-)) and I used a big glass reactor so don't pay so much attention to the amounts the original synth posted here has the correct amounts of products, focus on the process only.

Synthesis:

1. Solution IPA/H2O 2:1 (10,4L) was added to the reactor and stir at room temp.
2. NaBH4 (500gr) was added at once while stirring.
3. P2NP (287gr) was added in small portions, so that the temperature of the mixture did not exceed 60 *С.
4. CuCl2 (30 g) in water (57,50 ml) was added at once the temperature of the mixture did not exceed 80 *С.
5. Thereafter, reaction was then held at 80 °C for 30 minutes using external heating.
6. The mixture is filtered with Buchner funnel to clean it from the solid waste of the CuCl2
7. 25% water solution of NaOH (2,3 liters) was added to reaction mixture stir 5 min and once stirring stopped leave separate phases 1 hour.
8. The aqueous phase was thereafter extracted with 2,3 liters of IPA.
9. The first layer separated is mixed with the IPA extraction and the mixture dried with anhydrous sodium sulfate, filtered with Buchner funnel.
10. IPA was evaporated on vacuum to an oil.
11. Water is added to the oil to make steam distillation.
12. The distilled mixture is extracted twice with DCM(around 250ml of DCM for each 2 liters of mixture)
13. Extraction is evaporated on vacuum in rotavap until gets off all the DCM.
14. 254gr of Amphetamine freebase are obtained(transparent oil with PH 13)
15. The cooled freebase is mixed with cold methanol(533ml).
16. 34,5 ml of cooled pure sulfuric acid was added slow dropwise while strong stirring until PH 6 during this process an increasingly dense paste is formed.
17. 790gr of amphetamine "pasta" are obtained.
18. The mixture was put in the freezer for 12 hours.
19. After this 12 hours you can choose if filter it and dry it to obtain the amphetamine sulfate(wash it with acetone with this clean and pure result won't change anything), or directly keep it as "pasta" form in freezer.
20. To consume the product from the "pasta" form take and small portion of it and spread it for example on a sheet of paper or on a hot plate until it dries.

 

[G.Patton]

254gr of Amphetamine freebase are obtained(transparent oil with PH 13)

btcboss2022Did you get 121% yield? Are you sure that it is grams, maybe milliliters (in this case it is 107%)?

 

[btcboss2022]

Did you got 121% yield? Are you sure that it is grams, maybe milliliters (in this case it is 107%)?

G.Patton100% sure in grams next batch I will make pics. I got 254gr of freebase from 287gr of P2NP.

 

[G.Patton]

100% sure in grams next batch I will make pics. I got 254gr of freebase from 287gr of P2NP.

btcboss2022You are wizzard or it is not pure amph oil =)

 

[btcboss2022]

It's pure because it was distilled and I got 790gr of amphetamine paste and 760gr after 12 hours in the frezzer that is practically the best yield expected from freebase I don't have the dried sulfate weight because I won't dry it all in 1 time, the only thing could be in the oil is a small amount of water and very very small amount of DCM not completely distilled nothing else. Anyway next batch all will be documented(except magic things from wizzards of course ;-)joking)

 

[btcboss2022]

Here are the exactly details how I did, I must did it in these amounts because I didn't had enough sodium borohydride( new order arriving ;-)) and I used a big glass reactor so don't pay so much attention to the amounts the original synth posted here has the correct amounts of products, focus on the process only.

Synthesis:

1. Solution IPA/H2O 2:1 (10,4L) was added to the reactor and stir at room temp.
2. NaBH4 (500gr) was added at once while stirring.
3. P2NP (287gr) was added in small portions, so that the temperature of the mixture did not exceed 60 *С.
4. CuCl2 (30 g) in water (57,50 ml) was added at once the temperature of the mixture did not exceed 80 *С.
5. Thereafter, reaction was then held at 80 °C for 30 minutes using external heating.
6. The mixture is filtered with Buchner funnel to clean it from the solid waste of the CuCl2
7. 25% water solution of NaOH (2,3 liters) was added to reaction mixture stir 5 min and once stirring stopped leave separate phases 1 hour.
8. The aqueous phase was thereafter extracted with 2,3 liters of IPA.
9. The first layer separated is mixed with the IPA extraction and the mixture dried with anhydrous sodium sulfate, filtered with Buchner funnel.
10. IPA was evaporated on vacuum to an oil.
11. Water is added to the oil to make steam distillation.
12. The distilled mixture is extracted twice with DCM(around 250ml of DCM for each 2 liters of mixture)
13. Extraction is evaporated on vacuum in rotavap until gets off all the DCM.
14. 254gr of Amphetamine freebase are obtained(transparent oil with PH 13)
15. The cooled freebase is mixed with cold methanol(533ml).
16. 34,5 ml of cooled pure sulfuric acid was added slow dropwise while strong stirring until PH 6 during this process an increasingly dense paste is formed.
17. 790gr of amphetamine "pasta" are obtained.
18. The mixture was put in the freezer for 12 hours.
19. After this 12 hours you can choose if filter it and dry it to obtain the amphetamine sulfate(wash it with acetone with this clean and pure result won't change anything), or directly keep it as "pasta" form in freezer.
20. To consume the product from the "pasta" form take and small portion of it and spread it for example on a sheet of paper or on a hot plate until it dries.

btcboss2022I received some private messages with questions about the proportions of my process and I think is better to clarify it in the public post in that way you will understand why I did it in that way and how:

1- I have a 100L glass reactor and the first cross of the stirrer to move liquid is around 10L that means that less than 10l can't be stirred in my reactor.

2- The day of the synth I only had 500gr of NaBH4 that means 3,478 times less product than in the original synth(1739gr of Nabh4).

3- If you calculate the original synth proportions divided in 3,478 won't be the min 10L that I need for my reactor so I decided to make all proportions with 3,478 except water and IPA mixture because this wouldn't affect the process only time of distillation. I used water-IPA mixture(18L)/3,478=5,175L*2.

4- In short I made exactly the original proportions divided 3,478 due my NaBH4 stock except the water-IPA mixture that I used the double that I should use to be able to stir it in my reactor.

In the next batch I will reproduce again exactly that process with pics to show how the weights, amounts and yield are exactly as I detailed, in the next batch of the next one I will do it exactly the original synth to check if yield change but I'm practically sure that it wouldn't change.

Thanks.

 

[Taimo]

Great Instruction, i will be taste this way too the next days.
Greez

 

[Montecristo]

is the aqueous layer bottom or top in this reaction?

 

[Montecristo]

is the aqueous layer bottom or top in this reaction?

thatfellonokay i now see aqueous layer is bottom. was hard to see when i didnt filter it before basifying, now it is obvious.

 

[Montecristo]

i didnt get much salt precipitate out when i added phosphoric acid on my 67g p2np batch.
will this change during freeze? i thought i had followed instructions pretty well.
after p2np addition is complete do you go straight to cucl? or should i wait for it to stop reacting?
i shook it up after adding the lye and left it for about an hour, and when extracting with ipa i let it separate and then mixed again 3/4 times.
i vacuum distilled off the ipa @ 50-60oC , was this too hot?
maybe i acidified it too quick, as my sep funeel still had the aqueous layer ( i am doing 2 ipa extractions just in case) so i used a syringe and it wasnt dropwise exactly..
any ideas? i will update after its been in freezer overnight

 

[Montecristo]

I received some private messages with questions about the proportions of my process and I think is better to clarify it in the public post in that way you will understand why I did it in that way and how:

1- I have a 100L glass reactor and the first cross of the stirrer to move liquid is around 10L that means that less than 10l can't be stirred in my reactor.

2- The day of the synth I only had 500gr of NaBH4 that means 3,478 times less product than in the original synth(1739gr of Nabh4).

3- If you calculate the original synth proportions divided in 3,478 won't be the min 10L that I need for my reactor so I decided to make all proportions with 3,478 except water and IPA mixture because this wouldn't affect the process only time of distillation. I used water-IPA mixture(18L)/3,478=5,175L*2.

4- In short I made exactly the original proportions divided 3,478 due my NaBH4 stock except the water-IPA mixture that I used the double that I should use to be able to stir it in my reactor.

In the next batch I will reproduce again exactly that process with pics to show how the weights, amounts and yield are exactly as I detailed, in the next batch of the next one I will do it exactly the original synth to check if yield change but I'm practically sure that it wouldn't change.

Thanks.

btcboss2022any ideas?

 

[Montecristo]

any ideas?

Is your NaBH4 dissolved in IPA/H2O? In this case, answer - no. The better thing which you can do - put your mixture in fridge.

G.Patton