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

[mithyl2]

in the video novator says that around half of the 26.25g CuCl2 solution will be enough to 'cease' the black copper oxide formation.

does he actually use all of the CuCl2 solution, or only half of it?

(the last synth i did i added the CuCl2 solution in an unmeasured amount until the black copper oxide forms at the bottom of the reaction mix. i have yet to determine the quality and yield of the final product).

 

[InLikeFlynn]

Whatever you do, do it on a mg or gram scale first just so you can see what’s going on. That’s a lot of product to waste if you mess up somewhere.

 

[mithyl2]

I always appreciate tips from real experience. I haven't tried dry IPA yet

what is your source of p2np?

 

[InLikeFlynn]

Found it on eBay. Currently in the process of teaching myself how to make it.

 

[mithyl2]

has anyone else had a much larger amount of substance precipitate at the last step?

after i did the precipitation step with phosphoric acid i had more than 4 times the amount of what should be amphetamine precipitating

 

[Gordon Ramsay]

Very interesting, I'll observe and wait for an explenation of the experts on this I have heared typical street rumors as to the fact that phosphoric acid is supposed to increase yield but I'd wonder why it would yield more and also what effect this would have on the purity of the product. Amphetamines from phosphroic acid are supposed to be a little weaker, aren't they?

 

[mithyl2]

I tried to do a melting point determination but i had some problems. when i used the paraffin wax it would already be too hot once melted, and the p2np i had in the capillary tube would immediately have melted before i could record a temp. When i used silicone oil as a heating medium instead of the wax i couldn't see the p2np inside the capillary tube at all when it was immersed in the silicone oil.

anything else i can do or any alterations i can make to accurately measure the melting point?

 

[OrgUnikum]

1 g Amphetamine Sulfate contains 720 mg Amphetamine
1 g Amphetamine Monophosphate contains 570 mg Amphetamine
This might be an explanaition.

 

[mithyl2]

I think it's probably from where I contaminated the p2np with sodium bisulfite during the re-crystallization stage. (adding it to etoh while the p2np is dissolved as a way of removing specific impurities). I used far to much of it (an amount equal to the amount of p2np i had, when i think i need to use about 5%).
my p2np looks and smells as it should if it was really pure though.

i did synthesize a very small batch (my very first synthesis of amphetamine) with p2np that hadn't been potentially contaminated, and where everything else about this synthesis was the same as all of the other ones I did with the (most likely) contaminated p2np. i got a 30% yield, which would indicate a poor synthesis (i made a few mistakes as one is prone to for the first time) but otherwise more or less in line with what to expect yield wise.

 

[V€ctor Company]

Sorry, I have another noob chemist question

What purity does the acetone and sulfuric acid need to be?

I know a hardware store in my town which sells this extremely high purity sulfuric acid, let's say the purity of the sulfuric acid for this synthesis has to be 50%, could I just dilute the concentrated form with water?

 

[InLikeFlynn]

You want as close to pure reagents as possible. No you do not want to dilute the sulfuric acid with water, in fact you would want to make sure there is little to no water in the sulfuric acid at all. Your acetone also should be anhydrous (dry) and of decent purity with no other chemicals mixed in

 

[V€ctor Company]

Thank you so much for the help guys, much appreciated

 

[Cctim]

Can someone explain how he connected the hoses to transfer the liquid. so that the liquid does not flow into the pump. Does he used a special Ventil or a trap in the video ?

 

[InLikeFlynn]

AFAIK it is a liquid transfer pump of some sort designed specifically to move liquid and is separate from a vacuum filtration pump (I think)

Depending on the scale you’re synthesizing at, chemists wont usually need it and can do without. You can replace all the liquid pumping with more traditional methods like dumping/decanting things directly into flasks and separation funnels or using gravity filtration to get the big copper pieces out

 

[Cctim]

how much does nabh4 cost you? Is this method really worth it if I can get 1liter base for 1200 euros?

 

[Sig]

How match freebase a-oil can you make in a 50 liter glas reactor and in how many time ?

 

[Mr.Magic]

Hi, I'm fairly new to organic chemistry (9 month or so now, no other experience in chemistry )and have synthesized amphetamine via the Al/Hg route a few dozen times in the last couple of months.

I was able to reduce up to 120g of P2NP in a 20L round bottom flask. The purity of the end product was phenomenal in the last syntheses.
Most of the time I only had to purify the amphetamine sulfate once pro forma with acetone because it was already so white.

I found the NaBH4/CuCl²-route interesting because I have a great deal of respect for working with mercury, it had already led to a violent exothermic reaction three times, a large amount was distributed throughout the room and I would like to do without it in future.

The reduction with NaBH4/CuCl² also allows a significantly higher yield with a flask that is only half the size.
So far I have synthesized three times. The first time 80g P2NP, the second time 200g P2NP and the last time 250g P2NP.
The last one was the best of all, as I managed to stick exactly to the temperatures.

What I should also mention is that in order to shorten the process of administering P2NP, I place the flask in a large container full of ice, which I then heat over a hotplate. I was able to fill the entire 250g of P2NP into the flask in a good three quarters of an hour without getting above the 60°C mark. Does this affect the reaction with the Borohydride?

Despite all the care taken, the sulfate has a somewhat sweet, pungent smell at the end, despite its snow-white color. The consistency is also much more crystalline, crunching softly when crushed.
I have cleaned it several times with acetone and DCM, filtered it in a Buchner funnel, etc.
It definitely seems that another salt has joined the sulfate.

Has something similar ever happened to you?

Is it possible that the Sodium Borohydride, if not completely dissolved, mixes with the amphetamine freebase and is converted to a sodium salt when neutralized with H²SO4?
The stuff also burns badly in the nose. A friend had watery nasal mucus running out of his nose for several minutes immediately after taking a drag.

And now the real question: if there is another salt in it, how or what method can I use to separate the two substances?
I'm slowly coming to the end of my tether.

Thank you in advance for your patience in reading the whole text

I am grateful for any advice.

Mr.Magic

 

[OrgUnikum]

Ammonium sulfate or sodium sulfate contamination, I would for the burning guess ammonium sulfate. You have to dissolve the Amph-base in an solvent like Toluene or Xylene and then wash it with water to remove the ammonia. As Ammonia is very very water soluble but Amph base is almost not at all so if you are generous with the Xylene like 5 times the amount of base, you can wash out the ammonia with two washes water of the same amount as the base is. Completely and without losses.
Also steamdistillation of the base is needed to get rid of the dimeric byproduct.

Rolled into one, steamdistill the base directly from the flask, it will come over easily and completely then add Xylene 5 time the amount of the oil, separate the two layers and add water (as much as the oil was) shake and wait, separate and now you have Amph base fre from Ammonia, any sodium and the byproduct from step one.

 

[WillD]

Before adding the copper salt, you can neutralize the borohydride with a little acid. Or dilute the mixture with water to extract and wash the extract from excess salts. Afterwards you can work with pure extract and copper salts (there are other reagents for this).

 

[WillD]

Washing with water after the first stage and extraction in general is desirable to obtain a pure product without any burning.

 

[mithyl2]

is this as simple as adding water after all of the boro and p2np has been added, and then continuing with the synthesis as normal?

could you elaborate a little?

 

[WillD]

Carefully dilute the reaction with water, extract an intermediate product from the mixture using ethylacetate (as an example) for use in the next reaction.

 

[mithyl2]

Apologies if I'm being stupid and I don't want to be annonying with too many noob questions, but do you mean extracting the amphetamine with ethylacetate from the ipa mixture that has just been seperated from the black copper oxide?

 

[chenfei]

Can anyone help me write the formula?

 

[OrgUnikum]

Some theoretical background: P2NP is a so called Nitroalkene what means there s a double bond in the molecule. To get this to the Amine first this double bond is reduced forming a Nitroalkane. The Nitroalkane is reduced to the Amine by NaBH4/Cu(II) without issues. The problem is in the first reduction of this double bond as there is a competing reaction taking place (I spare you the details, its a "Michaels addition"). To solve the problem (partly) a huge amount of NaBH4 is used and the reaction runs hot and fast, it is a race: The faster one gets to the Alkane the less side-reaction. Nevertheless the side reaction cannot be completely eliminated this way. Also the huge amount of NaBH4 needed is wasteful, the reaction volume is huge too, runaways are possible.... Better then the acidic Al/Hg but far from perfect.

After quite some reading up on this I think I know a way to solve some of this. I would try it myself, but I have no P2NP at the moment and I do not want to buy something like this just now for other reasons. Well I tell how I would try this:

60 g NaBH4 and 500 g silica gel or diatomeous earth (chromatography quality) and 200 ml DCM are mixed thoroughly using a kitchen-dough kneader and put in a 3 liter flask.with overhead stirrer. IPA is added to make a stirable slurry and then P2NP 100 g in IPA is dripped in keeping the temperature at 25°C or below. Coo so needed.

There are plenty od wxamples for this reaction scheme and it is used to prevent exactly this kind of side reaction from happening. The unwanted reaction is caused mostly due to the ph of the reaction being to alkaline. The silica-gel being acidic lets the reaction take place on the surface of the gel and there ph is about 3 although the solvent is much more alkaline.

After all the P2NP was added the reaction is stirred (as slurry) until the yellow color of P2NP is completely gone. (if it does not go, add some more NaBH4, no problem)

Then more IPA is added, the CuCl2, 6 g, and 30 g more NaBH4 and the rest is the same as known.

Advantages are obvious, I bet with some optimizing NaBH4 and volume of reaction can be reduced further. It will work the better the better the NaBH4 is impregnated onto the the silica gel.

I would recommend to always steamdistill or vacuum distill the amphetamine base from any NaBH4 reduction of P2NP (same if using Al/Hg) as otherwise there will be some contamination by unpleasant dimeric products, the side reaction can be reduced but its nigh to impossible to get rid of it (using NaBH4 at least).

I read here that copper oxide is precipitating as black powder. This seems to me a bit strange, why should this happen in presence of a strong reducing agent? I say thats metallic copper nano-particles, the salt reduced to the metal, those particles do the actual reducing job, nitro-alkane to amine utilizing hydrogen supplied by NaBH4. But I might be wrong here, I did not look so closely into this part as it is not the problem.

If somebody would try this, would be great, or somebody in the EU donate me some P2NP and I try it myself and post the results.

 

[zeus]

I can give you 50g if you can't get it. I will try this method when have the possibility and will share the results here.

 

[Mr.Magic]

@OrgUnikum: If you don't need big amounts of P2NP, I can give you up to 50g for free. PM me for further details