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Author: Subject: Reductive amination of L-PAC
jon
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[*] posted on 9-1-2007 at 18:02


here was the reference I was talking about earlier it uses ammonium formate in a CTH with zinc.
Journal of chemical research, synopses, 2003, 6, 332-334 "zinc/ammonium formate a new facile system for the rapid and selective reduction of oximes to amines (K. Abiraj; D. Channe Gowda)
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roamingnome
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[*] posted on 9-1-2007 at 18:35


i can respect pepper

substituted PDC biotransformations are logically the next inquiry

yes i currently champion microwaves. I desire to know the most direct way between two points, but in the end youll find me lost on the scenic route.....

reducing the ketone group to the desired R group might be the right move... then work on the OH group in any mannor you fancy... i bet you got it figured out...
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roamingnome
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[*] posted on 10-3-2007 at 11:50
fly ash.....


no, you dont need to run out and buy fly paper as i first thought....


http://www.arkat-usa.org/home.aspx?VIEW=MANUSCRIPT&MSID=...

Table 4. Microwave assisted formation of Schiff bases catalyzed by Activated Fly ash

who is brave enough to toss the lpac into the crater of fly ash..... ... the gods demand a sacrafice......rumble rumble....
possible mudslide....and rain...
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jon
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[*] posted on 10-3-2007 at 23:14


I was thinking tht zinc/ammonium formate process would be perfect for something like this it's procedure is on rhodium's mirror
here:
http://www.erowid.org/archive/rhodium/chemistry/oxime2amine....

and here's one too
JOC 57, 6324 (1992)

At room temperature with stirring, Zinc dust (74 mg) was added to a solution of
the oxime (44mg, 0.185 mmol) in 2 ml glacial acetic acid. Stirring was continued
for another 15 minutes. The reaction mixture was then filtered through a sintered
glass funnel with suction. The filtrate was concentrated under vacuum to afford
the amine as an oil (37mg, 0.166 mmol, 90% yield).

all very doable

[Edited on 11-3-2007 by jon]

[Edited on 11-3-2007 by jon]
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hamdan
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[*] posted on 16-3-2007 at 07:52


please i want preparation diisopropyl amine without pressure
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[*] posted on 1-2-2008 at 07:49


Recently in a reductive amination experiment I tried using the methylamine HCL which was put in solution with water and methanol.........the catalytic reduction of the material didn't happened , hence upon adding some concentrated NaOH slowly and covering the vessel the amine gas was produced and was consumed in the water alcohol L-PAC solution making the solution a grenish yellow with the L-Pac sitting in the bottom.......the hydrogenation did occurred but slower than it I had used plain methanol with my methylamine dissolved in it.....i was trying to prove that reductive methylation of L-PAC does occur under catalytic hydrogenation using Pd/C 10% and of course with molar ratios of Methylamine 2:1 with L-PAC.

.............picture of resulting un recrystalized ephedrine.







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Ephoton
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[*] posted on 12-2-2008 at 03:59


that is very nice solo :) very clean for an un recrystalised product. I still wonder if
one is going for the psuedo unless your absolutly wanting a dextro product would it not be a lot easier to aim for the ketone then do the whole reductive alkylation.
I would love some info on how you did the broth though its hard to tell but that looks like a fair amount :)
oh just a thought fly ash your not thinking burnt winged things are you. thats nearly as good as distilling ants.

[Edited on 12-2-2008 by Ephoton]




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azo
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[*] posted on 12-2-2008 at 19:42
reduction lpac


hi ephoton

just a thought .. solo is doing a reductive amination of a ketone l/pac
if you are doing a reductive amination of lpac you are always going to get a racemic product
to me if you only want the dextro product you would have to seperate it using tartaric acid when it is reduced to meth
another thing if you are going to reduce the imine formed between lpac and methylamine with pt and h2 i cant see how it would not reduce the hydoxyl group at the same time
as you can reduce ephedrine with catalytic hydogenation

thank you all for my first post ;)
;););):cool:
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[*] posted on 12-2-2008 at 20:43


Quote:
Originally posted by azo
if you are going to reduce the imine formed between lpac and methylamine with pt and h2 i cant see how it would not reduce the hydoxyl group at the same time
as you can reduce ephedrine with catalytic hydogenation

:


Maybe by reading the material found with the enclosed link , you will understand why it won't................solo

http://www.erowid.org/archive/rhodium/chemistry/ephedrine.ca...




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[*] posted on 12-2-2008 at 21:20


I think its reductive alkylation that makes a racemate product not the reduction of
an opticaly pure imine. I might be wrong on this but I think there would be a difference.
organikum was mentioning something along those lines I belive. though if you have
some docs to show that this is not the case I would love to see them. If not I guess the only way to tell is to form the imine and let stand for a period of time then reduce and
treat with either d or l tartaric acid. so your saying that any kind of reduction of the hydroxyl needs to go via a halide swap.




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[*] posted on 14-2-2008 at 03:12
lpac


hear are sum references you would like see

this might help

The synthesis of either amphetamine or methamphetamine from P2P, regardless of the synthetic procedure used, will give a racemic mixture. However, when using ephedrine as the precursor, its chirality will determine the chirality of the methamphetamine formed. Retention of configuration will be observed during the reduction and this has been verified in the conversion of phenylpropanolamine to amphetamine.81 Extensive reports characterizing the enantiomeric composition of illicit amphetamine or methamphetamine have not been reported. Analytical methods are available for characterizing each enantiomer. However, this is not routinely done by the forensic drug chemist since the law currently treats the d and I isomers of both amines as Schedule II drugs unless present in the appropriate drug formulation.
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Ephoton
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[*] posted on 19-2-2008 at 23:26


hmm thats not a reference but a straight out plagerism that has nothing to do with ketols. note that P2P is a ketone and
by defanition of a ketone it has no chirality so there for leads to a mixture of isomers. now if you have a look at the subject of this thread you will notice an L before the PAC ie levo phenyl acetyl carbonol. notice the ol at the end of this chemicals name.
this means it is an alcohol. now to my knowlage and this is why I asked for some refs and I mean in the regards to ketols not ketones (big difference if you take what I just said to heart),
the two bonds from the oxygen that are attached to the second
carbon make the oxygen cycle around the carbon. now if
it is possible to actualy have such a thing as L-PAC then the
hydroxyl group would have to stabalise this. This is pritty new
terratory for me as im not realy into this kind of stuff I just found
it interesting how one could make the ketol from a ferment in the first place and still manage to keep its chirality.

so lets review the synth of L-PAC from ferment.

one if it is done in the dark and kept reasonably cold and acidic
you will keep the levo chirality. two if this product then has
any kind of energy submited to it, it will racermise.
now the questions I have been proposing and with out some
seriouse refs that deal exactly with ketols that form imine alcohols or oxime alcohols will have to be tested is. does the formation of these secondary double bonded nitrogen primary
alcohol compounds create a racemate and two if not can they
be reduced to an opticaly pure substance.

I kind of take most of what org says at face value to be honest.
I think he would know the difference between products.

the refs we need are from the psuedo ephedrine manufacture
patents. dambed if I can be bothered looking them up on espace but I know org probably did. so as I said I take his
word at face value. I can not see the pham industry doing it
this way if they could use allylbenzene and keep chirality if
this process does not.


no refs just straight logic.

but I think if you wish to find out for sure you either have to do
the tests or find the patents.
this is new territory for the hivers. they never realy worked
this one out it was jacked I think then org.

just to add to what i said so I dont look like my post above was not with out thought. I think that the energy in the reduction might make a racemate of the ketol not the imine alcohol. but on second thoughts ferments are reductive anyway so I am probably wrong and you could do a reductive alkylation and keep chirality. I would say your biggest enemy in creating an opticaly pure substance other than heat and light is the fact that the amine that you are
attaching to the ketal group is basic.

[Edited on 20-2-2008 by Ephoton]




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R.Esposito
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[*] posted on 28-11-2012 at 05:14


hi... i have industrial bottle with monomethylamine and now i apllying methylamine by pressure... I am not able to calculate the ideal ratio of methylamine, because he can not keep ... I can apply it to ethanol ... tell someone how much I could use for example methylamine in the application of industrial bottle directly into the reactor? I use liquid output bottles ...
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[*] posted on 28-11-2012 at 05:59


....try weighing it ...before and after you add the gas methylamine....solo



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[*] posted on 3-12-2012 at 23:51


a few kilos of crushed ice and some salt should cool your gasbottle nicely below 6°C and the methylamine will be a liquid.
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[*] posted on 5-12-2012 at 13:53


Hamdan. Di-phenylisopropyl-methylamines apparently have some use as analgesics. The final structures resembling those of opiates. And, should you use inadequate amounts of methylamine in your reductive aminations, you will surely produce some.

It was with these materials in mind that Henzelman crafted one of his classic synthesis. Apparently, methods other than catalytic hydrogenation, do not work well for producing such materials (according to Shulgin). High pressures however, are not required.

Physiologically Active Secondary Amines. β-(o-Methoxyphenyl)-isopropyl-N-methylamine and Related Compounds.

http://bitnest.ca/Rhodium/pdf/2-meo-methamphetamine.pdf
[Edited on 5-12-2012 by zed]

[Edited on 5-12-2012 by zed]
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Jesse Pinkman
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[*] posted on 6-12-2012 at 13:41
Maybe Urushibara?


Which is the most appropriate method for the reductive amination of L-PAC in your opinion ?

IMO the Leuckart reaction will not yield the desired (nor)ephedrine, so this makes Pd/C and probably Urushibara nickel attractive but I have seen a mystery around Urushibara - here on Science Madness some say, that Urushibara works, others say that it doesn't work?


Quote:

Ketones and aldehydes can be reduced to their respective alcohols using Urushibara catalysts with hydrogen at atmospheric pressure and room temperature. (this states the attached paper)


Interesting, if I remember correctly the reduction of carbonyl compounds to the corresponding alcohols requires harsher conditions that the hydrogenation of imines to form amines.

Attachment: urushibara_nickel_eros.ru003.pdf (36kB)
This file has been downloaded 1327 times
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[*] posted on 6-12-2012 at 14:56


That may be so, Pinkman. As I recall, most ketones resist hydrogenation. NaBH4 performs the reduction readily, but may be a bit pricey to obtain.

Another possibility that is seldom used is Ketone+Isopropyl Alcohol+ plus Al-isopropoxide> distill.......

Acetone distills off; driving the reaction to completion.

If this reaction proved applicable to L-PAC, the product would be the 1,2-diol.
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[*] posted on 6-12-2012 at 15:34


l-PACcondensed with hydroxylamine (easily pepared from nitromethane) and this reduced to the amine by

- Al/Hg or Al/Ga (for those paranoid about mercury).
Yields fair to good, has the advantage that the raw extract from the biotransformation can be used directly avoiding hassle with workup which always likes to introduce razemisation...

- noble metal catalysts, Pd usually poisoned with sulfur or similar, preferably in supercritical CO2. Thats industrial and outa reach for most. Best results though.

- Rayney Nickel under elevated to high pressure. Same as above.

- Urushibara Nickel. Not so trivial in preparation as it seems but works with elevated pressure.

With nickel and noble metals it is advised to stir a heavy amount of Urushibara or Rayney nickel, activated but without pressure, heat and hydrogen source into the reaction mix. After some hours filter this out and proceed with the reduction as by the books.
The procedure removes/deactivates catalyst poisons and is for the challenged amateur the basically only way to get this going in decent yields.

regards
ORG
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[*] posted on 7-12-2012 at 02:09
Raney nickel/Formic acid


Or maybe the reduction of L-PAC oxime to amine using Raney nickel and Formic acid as hydrogen donor(if Raney Ni/Formic acid can reduce nitro to amine, it will also reduce the oxime):

http://www.erowid.org/archive/rhodium/chemistry/cth.nitro2amine.rani-hcooh.html

from : Selective Reduction of Nitro Compounds Using Formic Acid and Raney Nickel

Synth. Commun. 30(16), 2889-2895 (2000)

Quote:

Aliphatic and aromatic nitro compounds were selectively reduced to their corresponding amino derivatives in good yields using formic acid and Raney nickel. This system is found to be compatible with several sensitive functionalities such as halogens, -OH, -OCH3, -CHO, -COCH3, -COC6H5, -COOH, -COOEt, -CONH2, -CN, -CH=CH-COOH, -NHCOCH3. The reduction can be carried out not only with HCOOH but also with HCOONH4.




Quote:

A suspension of an appropriate nitro compounds (5 mmol) and Raney nickel (0.2-0.3g) in methanol or in any suitable solvent (3 mL) was stirred with 90% HCOOH (2.5 mL) or ammonium formate (0.5 g) at room temperature. After completion of the reaction (monitored by TLC), the mixture was filtered off. The organic layer was evaporated and the residue dissolve in CHCl3 or ether was washed with saturated NaCl to remove ammonium formate. The organic layer on evaporation gave the desired amino derivatives.


The authors say that there is no need for strong acidic media and pressure apparatus. :)

There is a similar approach for reductive amination with Pd/Formic acid. (uploaded paper)


One problem - this reaction will only produce primary amines, but if one wants secondary amines (in this case ephedrines)?
Maybe monomethylation of PPA with formaldehyde and another hydrogenation with Raney Ni/Formic acid, or direct reductive amination of L-PAC with methylamine and Raney Ni/Formic acid ?

Attachment: redamin.hcook-pd(oac)2.pdf (52kB)
This file has been downloaded 767 times

[Edited on 7-12-2012 by Jesse Pinkman]
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[*] posted on 19-2-2020 at 00:36


Quote: Originally posted by MEXCHEM2006  
The information came from the book : Secrets Of Methamphetamine Manufacture

.....One would think that the reductive alkylation of that phenylacetone derivative would yield d,l-ephedrine, and then that reduction of that d,l-ephedrine would then give d,l-meth. That same racemic meth that results from reductive alkylation of phenylacetone. (Your Uncle prefers the buzz produced by the racemate over the harsher, more nerve jangling buzz produced by d-meth.) Apparently, this isn't the case. The references for this process claim that solely l-ephedrine is produced, and then reduction of this l-ephedrine, which is identical to natural ephedrine, yields that potent but harsh d-meth.
The phenylpropanol-1-one-2 can be reductively alkylated to give l-ephedrine. Any one of several methods can be used, just as in the case of reductively alkylating phenylacetone to meth. Method number one has to be catalytic hydrogenation using platinum catalyst.
In the example taken from US Patent 1,956,950, the chemists place 300 ml of the distilled phenyl-propanol-1-one-2 in the hydrogenation bomb along with one gram of platinum catalyst, and 85 grams of 33% methylamine solution. They state that it's advantageous to add some ether to the hydrogenation solution. How much is some, they don't say. They then hydrogenate the solution in the usual manner, with up to 3 atmospheres of hydrogen pressure, and magnetic stirring of the contents of the hydrogenation bomb.
When absorption of hydrogen stops in two or three hours, the platinum catalyst is filtered out. Then the ethery hydrogenation mixture is shaken with a volume or two of 10% HCl solution to pull the ephedrine out of the ether and into the acid water, forming the HCl salt of ephedrine. The ether layer is separated off with a sep funnel, then the dilute acid is boiled away. The residue is diluted with a little alcohol, and then a lot more ether. Passing dry HCl through this mixture then gives crystals of pure ephedrine hydrochloride. Their yield was around 110 grams.
My commentary on this hydrogenation? That yield is awfully low. Using phenylacetone as a guide, one should be expecting a yield around 300 grams of ephedrine. What's up? Check out the amount of methylamine used. There are about two moles of the phenylacetone derivative, but they don't even use one mole of methylamine. It should be the other way around, an excess of methylamine. Perhaps this is how they only get l-ephedrine from the phenylacetone derivative. In any case, I'd much rather have 300 grams of racephedrine than 110 grams of 1-ephedrine. My thoughts are that one would be better served just going to Chapter Eleven, and just plug in this phenylacetone derivative for the regular phenylacetone. That means two or three moles of methylamine for each mole of phenylacetone, alcohol as solvent, and a bit more platinum catalyst in the mixture.
In the patent, they give another reductive alkylation example. They use amalgamated aluminum as the reducer, just like in Method Three in Chapter Twelve. They take 120 grams of the undistilled fermentation product containing the 1-phenylpropanol-1-one-2, and drip it over the course of two hours into a solution of 10 grams of methylamine in 500 ml of ether in the presence of 20 grams of activated aluminum amalgam. Simultaneously, they drip into the mixture 20 to 30 ml of water. Stirring of the mixture is required.
The vigorous reaction that sets in is moderated by periodic cooling. When the reaction is complete after a few hours, they filter the mixture to remove the aluminum. Then they shake the ether solution with 10% HCl solution to draw the ephedrine into the water. The ether layer is separated then the dilute acid boiled off. The residue is thinned with a little alcohol, then dissolved in a lot more ether. Bubbling with dry HCl gives 25 to 45 grams of 1-ephedrine hydrochloride crystals.
My commentary on this procedure is identical to the last one. So little methylamine used! I haven't tried this, but I would be surprised to say the least if more methylamine didn't greatly increase the yield of product. I would also think that any one of the activated aluminum procedures given in Chapter Twelve could be used, just by plugging in this phenylacetone derivative for the regular phenylacetone. Also the use of ether is to be avoided when possible.


I’m a newbie so excuse the ignorance, I would like to pick your brain, in his book Uncle Fester mentioned brewing ephedrine and than he speaks about using toluene as a solvent and when it comes to one of the reduction methods he speaks about using undistilled fermentation product as part of the reduction with aluminum amalgam, ether, methylamine, etc. I would like some clarification there by what he means by UNDISTILLED FERMENTATION PRODUCT is he talking about the product after removing the yeast but before using the solvent or is he talking about after using the solvent and than doing the first distillation before doing the vaccuum distillation? The same chapter of the book I’m asking about is the one I just quoted which was posted by Mexchem
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[*] posted on 19-2-2020 at 00:41


Found the information I needed from another forum posted by Orgy....

[Edited on 20-2-2020 by Hulagu khan]
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