Author Topic: Possibility a new route: Pse Dehydration to meth  (Read 315 times)

headstrong

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Possibility a new route: Pse Dehydration to meth
« on: March 21, 2010, 11:08:18 AM »

Below is the procedure to convert Pseudoephedrine/Ephedrine to P2P, from Rhodium archive;

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When ephedrine and related compounds are heated in strong aqueous acid, they are dehydrated to the enamine, which spontaneously can rearrange to the isomeric imine (Schiff Base), which then can be hydrolyzed into phenyl-2-propanone and an amine salt. As all the steps are reversible processes, the reaction equilibrium is driven towards the desired product by continuously removing the formed phenyl-2-propanone by the aid of steam distillation.
Ephedrine derivatives that can be used in this procedure include Ephedrine, Pseudoephedrine, Norephedrine and Norpseudoephedrine (Phenylpropanolamine). Many other metal salts can be used instead of the zinc chloride.

 

1025g 75% sulfuric acid was mixed with 1g ZnCl2, and 192g (1.16 mol) Ephedrine or Pseudoephedrine freebase was dissolved at a temperature of 50-100°C, and the reaction mixture was heated further to 145-150°C. At 125°C steam is passed through the solution to facilitate mixing of the contents. At 145°C the stream of steam is increased, and during 2.5-3 hours the phenylacetone is steam distilled from the reaction mixture. The the crude phenyl-2-propanone, which is free from propiophenone, is isolated by toluene extraction of the distillate. After distillation through a short vigreaux column, 130g (82%) of phenyl-2-propanone is isolated in a purity of 99.8%.

Basically the procedure above is one pot 2 step from pse/e to p2p, 1st step is dehydration pse to imine and 2nd step is imine hydrolysis to p2p and methylamine.
If 2nd step is not performed, imine is gotten, imine is known very easy to reduce/hydrogenate, moreover if compare to damn hydroxyl group.

So, the procedure from pse to meth may be something like;
1.   Pse dehydration to imine,
By strong acid like h2so4 or h3po4, 98% or more considering imine is very sensitive to water.
 
2.   Imine reduction/hydrogenation
May be by neutralized H2So4 with metal like zinc, in anhydrous alcohol, the flask is in ice bath. Or neutralized by anything that wont produced water, methylamine freebase?
Filter and then reduce by nabh4.
But if possible, another reducing agent instead of nabh4, an otc one. Will be very interesting if Sodium dithionite (Na2S2O4) can be used as reducing agent (like in Rhodium archive).

 
Notes;
1.   85% H3po3 is heated to almost anhydrous, can be done by heating it at temperature just above 149 c. pse freebase is added, stirred well, heat 80 c for 12 hrs.
Anhydrous IPA and urushibara nickel is added, reflux for 4 hrs. Extract the product, no oil is occurred when basify, solid freebase only, means the pse didn’t converted to enamine.

2.   85% h3po4 is heated to almost anhydrous, pse freebase is added, heat 149 c min for 3 hrs. Some precipitation is occured.
Anhydrous IPA and urushibara nickel is added, reflux for 4 hrs. 2 kind of product is obtained, one has a lower melting point than another, both are not pseudo (but it cant use as conclusion). So, pse dehydration by h3po4 should be performed at temperature above 149, and may be for 5 hours at 149c, or 3 hours at 160c, just maybe.


Every feedback will be much appreciated, about how to do, chemicals that should be used, even you can prove that this idea is only good on the paper  :)

Sedit

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Re: Possibility a new route: Pse Dehydration to meth
« Reply #1 on: March 22, 2010, 02:44:00 PM »
The dehydration requires the use of a lewis acid catalyst notably zinc cloride. The reaction is reversable so steam distillation of the formed Phenyl-2-propanal is required in order to isolate it. Your products are P2P and Methylamine sulfate from the dehydration as well. This is also a reversable reaction where the MeNH2*SO4 reforms the imine. I have thought about ways to reduce this insitu to afford the methylated amphetamine product but all I keep ariving at is the conclusion that in the presence of such stong acid you will just keep pushing the reaction towards dehydration. There is also the issue that in order to afford any decent yeilds an excess of methylamine would be needed and here it is only produced in 1/1 ratio.  I posted over at WD sometime ago about this as well and got no where other then kewls telling me how stupid is would be to attempt it yada yada...

I know it has potential to produce the ketone but direct reduction may be a little out of reach unless someone can come up with a way of doing so at elevated temperatures... Aq enviroment, Highly acidic enviroment.
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headstrong

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Re: Possibility a new route: Pse Dehydration to meth
« Reply #2 on: March 22, 2010, 04:09:38 PM »

Please correct me if I'm wrong...
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The reaction is reversable so steam distillation of the formed Phenyl-2-propanal is required in order to isolate it. Your products are P2P and Methylamine sulfate from the dehydration as well. This is also a reversable reaction where the MeNH2*SO4 reforms the imine.
Imine <=> ketone + amine, is reversible in the presence of water. The method in Rhodium archive is run in aqueous H2SO4, that's why steam is performed to distill/isolate any P2P formed.
But imine won't undergo into ketone + amine in absence of water. That's why i start from almost 100% H3PO4. (I have bad feeling if using 98%+ H2SO4.)
 
Quote
I have thought about ways to reduce this insitu to afford the methylated amphetamine product but all I keep ariving at is the conclusion that in the presence of such stong acid you will just keep pushing the reaction towards dehydration. There is also the issue that in order to afford any decent yeilds an excess of methylamine would be needed and here it is only produced in 1/1 ratio.  I posted over at WD sometime ago about this as well and got no where other then kewls telling me how stupid is would be to attempt it yada yada...
Excess methylamine is necessary to make imine from ketone, but here imine is already formed by dehydration of PSE.

There are 2 question in my mind when i do research about this topic;
1. can imine be formed, by  dehydration with H3PO4 or something else (pyrophosphoric acid,...), in absence of water since beginning.
2. if it can be, how to reduce said imine that is in H3PO4.


POSEIDON

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Re: Possibility a new route: Pse Dehydration to meth
« Reply #3 on: March 23, 2010, 10:19:03 PM »
HEADSTRONG Read this :
Oxidation of primary, secondary, and tertiary amines with neutral permanganate. Simple method for degrading amines to aldehydes and ketones (http://127.0.0.1/talk/index.php/topic,785.40.html)
Surjan S. Rawalay, Harold Shechter
Journal of Organic Chemistry
1967, 32  (10), pp 3129–3131
DOI: 10.1021/jo01285a042
The chemists are a strange class of mortals, impelled by an almost insane impulse to seek their pleasures amid smoke and vapour, soot and flame, poisons and poverty; yet among all these evils I seem to live so sweetly that may I die if I were to change places with the Persian king.
— Johann Joachim

headstrong

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Re: Possibility a new route: Pse Dehydration to meth
« Reply #4 on: March 24, 2010, 07:03:19 AM »
Thanks Poseidon,
I get 2 points from that paper,
1. nice procedure, an alternative for NaOCl stecker degradation.
2. amine containing alpha hydrogen can be oxidized rapidly to enamine-imine, but under this condition the schiff bases usually undergo addition of the parent amine to give ammonals and aminals. I should learn about aminal issue.
Please let  me know, if there's something you want to tell but lost from my attention.

Below is a patent about imine preparation-isolation, and the said ketimine is reduced to meth.

headstrong

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Re: Possibility a new route: Pse Dehydration to meth
« Reply #5 on: May 05, 2010, 02:36:09 PM »
I think i know the answer;
1. 50%-75% sulfuric acid was mixed with small amount  ZnCl2, and Ephedrine or Pseudoephedrine freebase was dissolved at a temperature of 50-100°C, and the reaction mixture was heated further to 145-150°C. Yielding p2p. No need to isolate the imine neither steam distillate.
2. extract p2p with Hexane, wash with Na2CO3 solution. Heat to evaporate Hexane.
3. reductive amination

But by this way nothing is new here, maybe just a bit simplification lol.
The benefits;
1. OTC chemicals
2. various target synthesis, n substitute amphetamine, like a legal substance n propyl amphetamine.

Sedit

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Re: Possibility a new route: Pse Dehydration to meth
« Reply #6 on: May 05, 2010, 02:53:19 PM »
The starting materials added without prior processing of the starting pill mass and the mixture is heated to affect the dehydration. After sometime passes steam is lead into the reaction flask and a distillate recieved showing an amber colored oil that floats on the surface.

Steam entering reaction proves to great and the H2SO4 concentration increases to the point where charing of the reaction becomes to great. The distillate reaks to all hell of a smell that can not be described other then nasty on top of the SO2 smell also present.

No attempt was made to isolate the yellow oil due to an overwhelming stench.

Quote
Below is a patent about imine preparation-isolation, and the said ketimine is reduced to meth.
But the question remains is if this can be isolated under the conditions of the dehydration. The reaction is reversible and I am not sure if one would be able to isolate the imine under the conditions needed to perform the dehydration without forcing the equilibrium in the wrong direction. Not to mention you have to make sure it does not proceed all the way to full dehydration in the process. Does anyone have thoughts in this area because its something that has had me thinking for sometime.
Perhaps Neutralization which still heated would work?


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2. various target synthesis, n substitute amphetamine, like a legal substance n propyl amphetamine.

And lets not forget the greatest thing you can do performing the reaction this way. Create a reasonable doubt that you are only creating Propyl amphetamine for your own personal use.
There once were some bees and you took all there stuff!
You pissed off the wasp now enough is enough!!!

headstrong

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Re: Possibility a new route: Pse Dehydration to meth
« Reply #7 on: May 06, 2010, 12:32:37 PM »
Quote
No attempt was made to isolate the yellow oil due to an overwhelming stench.
I can imagine that  ;D

Quote
But the question remains is if this can be isolated under the conditions of the dehydration. The reaction is reversible and I am not sure if one would be able to isolate the imine under the conditions needed to perform the dehydration without forcing the equilibrium in the wrong direction. Not to mention you have to make sure it does not proceed all the way to full dehydration in the process. Does anyone have thoughts in this area because its something that has had me thinking for sometime.
Perhaps Neutralization which still heated would work?
I. In that patent is forming imine in basic condition, the rxn can be forced to the desired direction by;
1. removing water, maybe by drying agent like CaO
2. excess of any precursor, in this case is methylamine because it's easier to make.
The isolation is fairly simple, only by evaporating methylamine. The problem to perform that patent is it's use liquid methylamine, but may be itcan be substitute by anhydrous methyalmine in alcohol.

II. In acid condition, by dehydrating E/PSE with H2SO4/H3PO4
A question, is imine can be formed in acid condition? If it can be, then the rxn can be forced to the desired direction by;
1. The Presence of methylamine. Note, Pseudoephedrine phosphate is soluble in 100% H3PO4 so possibility methylamine phosphate is soluble as well.
2. start with mixture of H3PO4 and H4P2O7 (pyrophosphoric acid), that is still easy to prepare, just by heating H3PO4.
The isolation can done by (wait.., imine can form salt like amine or not?), if it can form salt then crashing by a suitable solvent, if it can't then distillation is the answer. According to that patent, n-methylimine of phenylacetone is colorless liquid, BP 63-66 c.
But if imine can't be formed in acid condition, then a lot of effort with a poor yield since the rxn isn't reversible.
Too many "if then"  ;D.