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

[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]

Yes, 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!

 

[Pervitin]

Hello, I read some time now in this forum?thread and want everyone in this topic to ask what point of the synthesis is for him the most difficult/ important and on witch details everyone should pay attention to?

And in the video is no exactly shown, Is it better to use a reflux condenser for the synthesis?

 

[WinterDust]

No part is difficult in this synthesis, it is just about being careful so there won't be any accidents.

I have had them and wrote about them here in the thread for other people to not do the same thing.

Yes, you need to use reflux condenser.

 

[ElementalEnigma]

Exactly! You can skip reflux but you loose quality and I believe some for of side products form. Anyone find a variant with more euphoric effect form?

 

[Pervitin]

I read about problems with storing the pure freebase, over a couple of time its react. What have to be done to store it propably? Do I need an exsikkator?

 

[WinterDust]

For what reason do you need to store it?

Yes, is degenerates over time. The ideal storage would be in a vacuumcontainer stored inside a fridge.

 

[UWe9o12jkied91d]

Just store the stable sulphate salt and base it when needed

 

[WinterDust]

Here's a legit question in my opinion.

What would happen if we don't ad the catalyst (CuCl2) to the reaction?

Since it's a "booster", will it have effect on the yield?

 

[Melv99]

You'll end up with an intermediate and still need to reduce it with Zinc-HCL to the disired product.

 

[Felix34-73]

I want to try on a 1 liter scale
How many ml should the ratios be

 

[WinterDust]

If you would have taken the time and read through the thread, you would quickly find out that the reaction is linear in scaling.

 

[Mystery_chemistry]

can you add water after removing the ipa / freebase phase, bring it to ph 6 add a non-polar solvent. extract our product, raise the pH to 12-13 and evaporate the non-polar solvent from our freebase

 

[CasualChemist]

Hello, I decided to use this method in my first attempt to make amphetamine and also my very first synthesis ever.

Below is my detailed write-up of procedure scaled down to 5 g of P2NP. I'd be grateful if someone experienced could take a look and maybe give me some pointers on what I could do better next time.

1. 10 g of NaOH was added to 30 ml of distilled water in 100 ml beaker, mixed and left to cool.
2. 2,63 g of CuCL2x2H2O was added to 5 ml of distilled water in small weighing bottle and mixed.
3. 60 ml of IPA and 30 ml of dH2O was added to a 3-necked 500 ml round bottom flask. Flask was equipped with 0-150 °C glass thermometer, a 300 mm Liebeg condenser, third neck was closed with a glass stopper to be used later for additions.
4. 8,7 g of NaBH4 was added to the Reaction Mixture in one batch, under constant stirring.
5. Water bath was filled with refrigerated water to reach 16-17 °C.
6. 5 g of P2NP was ground in a mortar and slowly added to the RM, temperature didn't rise above 25 °C. Mixture was bubbling a lot, with small and abundant bubbles.
7. When no yellow crystals of P2NP were visible anymore in the RM, total of ~1,2 ml of CuCl2 solution was added drop-wise using a 1 ml Pasteur pipette. Each drop caused fizzing and made a small cloud of black/dark brown particles precipitating from the solution. Addition was stopped because it already exceeded initial plan of adding only 1 ml.
8. RBF with RM was placed in an oil bath (white mineral oil was used) and slowly heated to 72-76 °C under condenser running water at 16-17 °C. Magnetic stirrer was on the whole time. RM temperature was kept at this level for 30 minutes. White mist was visible escaping the condenser, a lot of solvent was dropping back to the RM. RM was left to cool with strong stirring on. RM has split into two layers. Bottom layer was still bubbling, black residue in form of small flakes settled between the layers, top layer was clear and calm.
9. Heat was reapplied, RM was heated to 80 °C and left to reflux again for 30 minutes. After this time layer separation disappeared and black/brown dusty residue settled to the bottom. Almost no liquid was dripping down the condenser this time.
10. Clear liquid from the top was decanted into a Büchner funnel with filter paper into a 250 ml Erlenmeyer flask, dark slurry from the bottom was discarded. Clear liquid was transferred into a 300 ml beaker.
11. 40 ml of 25% NaOH solution was added to the liquid under strong stirring, pH strips indicated pH of 10-11. Mixture was poured into a 250 ml separatory funnel and left to fully separate. Mixture was left to separate for 15 minutes, liquid was dripping from the valve so decision was made to start draining, it seemed to be finished at this point anyway.
12. Two clear, colorless layers emerged, bottom one contained some solids in form of sparse dusty particles, top one was completely clear. Bottom layer was discarded and the top one (<50 ml) was collected into o 250 ml beaker.
13. 2 ml of 85% ortho-phosphoric acid was mixed with 2 ml of ice-cold acetone in a 100 ml beaker.
14. Acid solution was slowly added to the amphetamine oil/IPA solution using a 3 ml Pasteur pipette.
15. Snow white precipitate caused the mixture to thicken so much, the magnetic sitter couldn't mix it anymore. 20 ml of ice-cold acetone was added to thin-out the solution. Mixture was left outside for approx. 1 h, temperature was 2-3 °C.
16. Mixture was poured over a filter paper in a Büchner funnel, solvent was captured in a 250 ml Erlenmeyer flask.
17. Filtered liquid was transferred back to the beaker with the remaining product. Solution's pH was checked with test strips and more acid solution was added until more white salt precipitated. Routine was repeated until test strips shown pH of 6-7, probably still around 7.
18. When solvent stopped dripping from the Büchner funnel, snow white paste was transferred into a small crystalizing dish and left to dry under room conditions overnight.
19. Process was finished 20h later by heating crystalizing dish to 50 °C using a 3D-printer heated bed in the last 3 hours. Product reached constant weight and the yield at this point was 3,23 g of pure white powder with faint "fishy" smell.
20. Dry product was mixed with 50 ml of IPA and left to stir for approx. 3 hours in room temperature. Product was filtered over a filter paper in a Büchner funnel and the remaining paste was washed with 50 ml of cold acetone.
21. Product was dried on a heated bed at 50 °C, final weight was 2,82 g. Total loss in washing process was 0,39 g or 12% of the product. The final yield corresponds to a total efficiency of 40%. Product almost completely lost its smell. It burns a bit when put on tongue and it causes burning sensation in nostrils and throat when snorted. Medicinal effect is strong even with tiny amounts.

I know I've messed something up in steps 7. to 9., maybe I've rushed things too much.

I think my yield could've been better if I'd add more acid in steps 14. to 17., but I only had pH strips with range 1-14 and the resolution wasn't good enough and I didn't want to spoil the product by overacidifation. I think I've lost some product with the dark sludge discarded in step 10., but I didn't want to spoil the quality of my end product so I'm okay with that.

 

[UWe9o12jkied91d]

you are overcooling and have a lot of unreacted starting material in the finished.As long as it's not foaming too hard let it rip, don't cool unless absolutely necessary, add as much propene as you can at a time, within reason, same as Cu solution.A good measure is letting RM reach 50-60 C during propene addition, apply cooling THEN continue adding propene + Cu sol. . This way the RM goes down in temp steadily and shoots up again with addition, letting you control the reaction temp to be more or less fixed at a toasty-yield-enhancing temp.

 

[CasualChemist]

I thought I've over cooled it. Instructions never mentioned that temperature MUST reach 60 °C, only not exceed it. That's why I thought it would be good idea to cool it from the beginning. I won't do that in the next batch, I'll follow your guides, thank you!

Shouldn't the rest of the P2NP and NaBH4 continue to react in step 9. though?

Do you suspect that because of this error my final product can be contaminated, even after washing with IPA and acetone? I've tested it for water solubility and it dissolves quickly, without a trace. Is there anything else I could test in clandestine conditions?

 

[UWe9o12jkied91d]

You could do TLC, I made my own plates from plastic credit card wrapped in aluminium foil and coated with stationary phase slurry, you can use glass panes etc Altough if you say it dissolves maybe it's reaction product between it and sulphuric acid.

Absolutely, P2NP is pretty hard to clean from precipitated sulphate, if you say it burns after washing even and it is white , not red (overacid) or yellow(unreacted base) than surley it is raw material contamination

 

[Melv99]

Thanks for your response and @Casualchemist writeup..

I myself have been keeping it way to cool on the initial adding of the propene as well. My first attempt went exactly like I anticipated. Or so I thought. But I believe when adding the acid, the xtals that formed in acetone and IPA were mostly Nacl or NaSulfate because of the Naoh also going into the Ipa layer.
So second time I extracted with a NP solvent and it still seem to be a mix of both disired product and some simple salt.
(Also suspect a bunch of unreacted FP2P stayed in the solvent layer since it stayed orangish/yellow)

To test I tried heating the f-amp sulfate before proceeding to other tests and some did melt as anticipated and left a salt that stayed in its salt form even when hit with high temps. Does anyone know if Amp sulfate melts as it decomposes or the amp melts and leave behind the sulfate salt? In this case 4F-P2NP was used. Which I’d assume acts fairly similar.

 

[nsrnsr]

How to solve the burning problem when the finished product burns? Thank you

 

[UWe9o12jkied91d]

Burning can mean many things, it can be raw material, over-acid, under-acid.
Check out amphetamine purity assement thread that may help you troubleshoot.

 

[nsrnsr]

The finished product will be burnt after burning. How to solve it? Thank you

 

[nsrnsr]

I mean after burning thank you~

 

[Pervitin]

My syntheses still bubling after adition of cucl2 and refluxing it. Should I still vacuum destill the ipa of or wait ?

 

[Melv99]

I added a small amount of CH₃COOH to kill the Nabh4 before filtering.

 

[Melv99]

Keep us posted.. I was able to distil off the IPA and very miniscule amount of product came over with the IPA. Finally got to see the oil floating. Since I didn't have a vacuum working at the time I extracted with a NP. Worked just find.

Interesting though was the yellow-ish orange color thst remain in the NP.. it smelled very sweet which It made me wonder if that was P2P that didn't get fully reduced.

 

[Pervitin]

Yeah I vacuum destilled it at the moment. I have clear product in the receiver, just like ipa. My oilbath is at 70 C, but steam temperature is at 50 C. Hope I fuked something up, because my magnetic stirrer was not strong enough and now I have a clear layer on top and this hard sludge on the ground. I think I have to invest in a kpg stirrer next time.