Reduction of L-PAC to ----

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onevegasdave
(Stranger)
05-01-04 17:10
No 504242




reduction of L-PAC to ----
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Swim has produced about 100g of L-PAC with the help of freindly Bee's...now the reduction to ---- is a little confusing. Which is the preferred ---- of reduction of the Bees that have done the L-Pac reduction. Comments, criticisms are welcomed

2 Heads r Better than 1

ChemoSabe
(Hive Addict)
05-01-04 17:23
No 504245




Organikum L-PAC
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All I can say is that you might find out with a search of Organikum & L-PAC

Good luck and congrats on the L-PAC production. It's the real wave of the future. Fuck pill extraction.

methylamine is another keyword that might get you somewhere

Country line dancing royally sucked until black people got ahold of it

DrLucifer
(Hive Bee)
05-02-04 03:08
No 504327




l-pac
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You will need to reductively aminate the raw l-pac juice to get l-ephedrine. From there, the path to ---- is your preferred choice obviously.
I havn't performed the bio-synth, but i hear the al/hg reduction is a preferred method.
If you dont mind, i have a few questions.
Did you treat your yeast with acid prior to fermentation?
What combination of nutrients did you utilise?
How much benzaldehyde did you add to obtain 100g?
Cheers, and congrats, i wish you luck

I'm a diamond that is tired, of all the faces i've aquired.

Organikum
(Wonderful Personality)
05-06-04 05:44
No 505265




Benzaldehyde -> L-PAC -> Ephedrine
(Rated as: good read)
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The article he spoke of is probably:

Biotransformation of benzaldehyde to l-phenylacetylcarbinol (l-PAC) by Torulaspora delbrueckii and conversion to ephedrine by microwave radiation
J. Technol. Biotechnol. 77, 137-140 (2002) DOI:10.1002/jctb.534

The article deals with the usual biosynthesis followed by microwave supported imine formation and reduction of the imine by NaBH4 in a microwave.

The claimed yields of the biosynthesis are to good to be true (maybe the are true but the technical effort is immense), the yields of the imine formation are lousy and the yields in the final NaBH4 reduction are ok.
A modificated household microwave oven was used.

btw. of course all reductive alkylations of l-PAC with methylamine end with ephedrine - what else?

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amalgum
(Hive Bee)
05-06-04 06:25
No 505270




One speculation SWIM has had in the past is...
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One speculation SWIM has had in the past is reduction of an imine formed between an l-pac ester and methylamine, to proceed straight to ----.

Would it be possible to somehow esterfy the alcohol group without disturbing the keto group (including ways to protect/de-protect the keto group) wich would allow proper imine formation when reacted with methylamine without fucking up the ester group (damn did I even word that right?)? Lets say for examples sake the l-PAC was reacted with acetic anhydride to make acetic ester of the alcohol group. Then that was added to an alcohol and gassed with methylamine to form the imine, then followed up with say Pd/C-ammonium formate reflux, reducing both imine and ester, turning imine to amine and removing the alcohol all at the same time proceeding directly to ----.

Is anything like that even remotely possible?

Organikum
(Wonderful Personality)
05-06-04 06:39
No 505272




A reduction of the preformed imine under ...
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A reduction of the preformed imine under (strong) acidic conditions with a powerful reducing agent (maybe Al/HG suffices, Pt/Pd will) should produce methedrine directly.
Hydroxyphenylacetones form stable imines, so the there is no attackable keto-group left. The hydroxy group of the imine is told to be prone to reduction in acidic environment - thats why usually alkaline conditions are used - to suppress the reduction of the -OH.
Not to forget: The pathway l-PAC - ephedrine - ---- is not straightforward but more two steps forward and one back, this is also true if done as "one pot" reaction.

Shareholder of Paranoid Fucks inc.

amalgum
(Hive Bee)
05-06-04 16:45
No 505394




Re: A reduction of the preformed imine under...
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A reduction of the preformed imine under (strong) acidic conditions with a powerful reducing agent (maybe Al/HG suffices, Pt/Pd will) should produce methedrine directly.

You think so? Like maybe a conglomeration of the catalytic hydrogenation methods for ephedrine with Pd catalyst and acid promoter (like H2SO4 or HClO4). Maybe preform the imine in alcohol, add Pd/C bring to reflux and slowly add the NH4COOH over time. When reduction of the imine is complete, maybe one could just cool it down, add acid and maybe some fresh catalyst, bring back to reflux and add more formate for reduction of the alcohol group (damn that was a long run on sentence).

Hydroxyphenylacetones form stable imines, so the there is no attackable keto-group left.

Yeah SWIM knows, what SWIM meant was will ESTERFICATION of some sort attack the keto group before imine formation. SWIM knows halogenation is probably out of the question as any halogenic acids will cause condensation of the ketone (if SWIM remembers correctly from reading about making phenylmethylbutenone from MEK and benzaldehyde). But SWIM forgot all about those catalytic hydrogenation documents for ephedrine that use acid promoter and Pd or Pt catalysts using straight ephedrine (no ester) as precursor. So it seems apparent that no esterfication would be required anyway (for a one pot reduction anyhow).

Not to forget: The pathway l-PAC - ephedrine - ---- is not straightforward but more two steps forward and one back, this is also true if done as "one pot" reaction.

What exactly do you mean?

Man if a one pot method can be developed, then like someone said above this pathway may very well be the wave of the future. SWIM is gonna have to tinker with this idea now. Now SWIM needs some benzaldehyde.....hrmmm. SWIM was always partial to the akabori process however, but has never tried it so only knows how it would work in theory. The speculations above are still only theory, and we all know chemistry more often than not deviates from theory (in reality that is).

Man I love this website. All we need is a bunch of smart chemists to keep on callaborating, and the drug war will never be won! I mean as far as ---- goes, we could make it from styrofoam cups and vinegar for christ sake (talk about starting from scratch!)! Are they gonna control those two?

borolithium
(Stranger)
05-06-04 22:45
No 505500




Borohydride reduction of L-PAC
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- The claimed yields of the biosynthesis are to good to be true (maybe the are true but the technical effort is immense), the yields of the imine formation are lousy and the yields in the final NaBH4 reduction are ok.
A modificated household microwave oven was used.[blue]

[black] I have read in the serious chemistry forum that the reductive amination of L-PAC to ephed is almost identical to the MDP2P aminations and that any of those techniques can be applied to the L-PAC.

With MDP2P, the borohydride reduction is very exothermic, requiring heavy cooling and slow additions of the borohydride over several hours under strong stirring. If cooled sufficiently, it is also high yielding.

Is this not the case with the L-PAC reduction? Does the reaction require energy from microwave radiation to proceed?

The borohydride reduction appears to be the best way to produce ephed in large quantities, as it is quite scalable and the availability of sodium borohydride is becoming more and more available, not only as an alternative energy source, but also for pulp and paper mills and waste water management. The HG/Al amalgamation on the other hand generates a lot of toxic waste and is better for small scale operations. I would imagine it is much harder to obtain mercury salts in large quantities and you may need to hire someone full time to cut up pie plates! If you're sloppy, enjoy the permament brain damage!

Raney nickel is a pain in the ass to get as well I understand.

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Organikum
(Wonderful Personality)
05-07-04 03:30
No 505552




Yes, of course , all methods which work for...
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Yes, of course , all methods which work for P2P or MDP2P will work for l-PAC too. But l-Pac has also the option of preforming a stable imine what doesnt apply for P2P and MDP2P.

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amalgum
(Hive Bee)
05-07-04 16:03
No 505653




Re: But l-Pac has also the option of ...
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But l-Pac has also the option of preforming a stable imine

Heh, thats music to swims ears!

borolithium
(Newbee)
05-07-04 20:49
No 505701




Pardon My NewBee Ignorance
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Organikum, what exactly does that mean to us in the scheme of things?

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Organikum
(Wonderful Personality)
05-08-04 03:38
No 505766




Re: Organikum, what exactly does that mean to...
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Organikum, what exactly does that mean to us in the scheme of things?

This says that there is a realistic chance that it is possible to form the imine from l-PAC by adding methylamine (called condensation) and to reduce this imine straight through to methedrine. Acidic conditions and a powerful reducing agent will be needed - Al/Hg maybee, Zn/HCl, or best noble metal catalysts (Pt/Pd). Maybe other catalysts might work too (H2S/HI), this I dont know.
Nevertheless there is strong evidence that the hydroxyl-group of an imine is easier reduced than the hydroxyl-group of the amine.

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amalgum
(Hive Bee)
05-08-04 16:21
No 505862




Hehe, add methylamine HCl to some methanol and
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Hehe, add methylamine HCl to some methanol and add equal molar amount of lye, filter off NaCl that precips. Throw on mag stirrer, and drip in l-PAC. From there, can someone say microwave assisted Pd/C with ammonium formate for reduction. Imine first, then add promoter acid and kick off that hydroxyl. Easy as pie. SWIM hopes this proves viable.

borolithium
(Newbee)
05-08-04 22:17
No 505918




But,,,,
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The lye additions to the methylamine hydrochloride will produce a fair bit of water. Won't that interfere with the reaction?

It would seem better to me if one used dry methanol and bubble methylamine gas through a drying tube of Magnesium Sulphate, then into a -20C solution, by liberating the methylamine HCL in a seperate vessel.

I would seem to think water is not a good thing in this type of reaction. Am I wrong?

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amalgum
(Hive Bee)
05-09-04 00:08
No 505927




It would be overkill to do all that drying.
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It would be overkill to do all that drying. When an imine gets formed, water is formed as a byproduct anyway which never seemed to hurt reduction (of the imine to amine least), esp. the Pd/C with NH4COOH reflux. SWIM doesn't think it would hurt reduction of the hydroxyl group either as it is most often reduced in an aqueous environment (look at HI/P reductions of ephedrine).

BOS
(Hive Bee)
05-10-04 08:26
No 506203




Another patent
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Patent WO03018531
Carry on from Co2 patent posted by Roger2003

This is an interesting read if not for only showing possibilities.

Not much use to the home handy man, but does touch upon reducing PAC to ---- etc.

Organikum
(Wonderful Personality)
05-10-04 09:56
No 506223




Re: but does touch upon reducing PAC to ----...
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but does touch upon reducing PAC to ----

where please?

Schnabufugl!

Rhodium
(Chief Bee)
05-18-04 11:18
No 507915




Benzaldehyde -> L-PAC -> PPA
(Rated as: excellent)
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Synthesis of (1RS,2SR)-(±)-2-Amino-1-phenyl-1-propanol from (R)-(-)-1-Hydroxy-1-phenyl-2-propanone
Prema M. Subramanian, Sunil K. Chatterjee and Mahesh C. Bhatia
J. Chem. Tech. Biotechnol. 39, 215-218 (1987) (https://www.rhodium.ws/chemistry/ppa.l-pac.raney-ni.html)

Abstract
Synthesis of (1RS,2SR)-(±)-2-amino-1-phenyl-1-propanol (2) by reductive amination of (R)-(-)-1-hydroxy-1-phenyl-2-propanone (1) using ammonia and Raney nickel as a catalyst was investigated. Compound 1 was produced by fermentation of molasses with a strain of yeast and benzaldehyde was added during the course of fermentation.

Also see Post 44728 (LaBTop: "Patent Collection: L-PAC Synthesis", Stimulants)

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aia2
(Stranger)
06-24-04 17:38
No 515219




Where can we go from our L-PAC?
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where please?

The "SUMMARY OF THE INVENTION" includes the following:

According to one embodiment of the invention, the amine (VI) is selected from the group consisting of ephedrine (R4 = OH, R5 = phenyl, R2 = methyl, R6 = R3 methyl), isoetharine (R4 = OH, R5 = 3,4-dihydroxyphenyl, R2 = ethyl, R6 = R3 = isopropyl), ritodrine (R4 = OH, R5 = 4- hydroxyphenyl, R2 = methyl, R6 = R3 = 2- (4- hydroxyphenyl) ethyl), methedrine (R4 = H, R5 = phenyl, R2 = methyl, R6 = R3 = methyl), fenfluramine (R4 = H, R5 = 3-trifluoromethylphenyl, R2 = methyl, R6=R3= ethyl) and propylhexedrine (R4 = H, R5 = cyclohexyl, R2 = methyl, R6 R3 = methyl). These compounds are preferably formed using hydrogen and a catalyst as the reductant, although they can be formed using a hydride reducing agent.

According to an alternative embodiment of the invention, the amine (VI) is selected from the group consisting of amphetamine, methoxamine, phenylpropanolamine, hydroxyamphetamine, ethylnorepinepherine and metaraminol. These compounds may be formed using a hydride reducing agent as the reductant.

I'm a Newbee, so please forgive and correct my errors. The imine that is formed from the L-PAC is 2-(methylamino)-1-phenyl-1-propanol, which needs to be reduced twice to get to methedrine. However, it looks to me like there will be ephedrine in situ because it is the result of a single reduction. How is this taking two steps forward and one step back?

Another question, why should this be done under strong acidic conditions?

--aia

ChemoSabe
(Hive Addict)
06-24-04 22:48
No 515276




L-Pac Questions
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aia2 axed...

Another question, why should this be done under strong acidic conditions?

I think Orgy somewhat covered this in one of his posts above by stating...

Hydroxyphenylacetones form stable imines, so the there is no attackable keto-group left. The hydroxy group of the imine is told to be prone to reduction in acidic environment - thats why usually alkaline conditions are used - to suppress the reduction of the -OH.

I really don't get your first question but if it's what I think it it is the answer is just be happy enough that you didn't have to deal with pill extraction.

He was just another tree in the forest whom nobody heard on his final fall

aia2
(Stranger)
06-25-04 00:33
No 515287




How much reduction
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I really don't get your first question but if it's what I think it it is the answer is just be happy enough that you didn't have to deal with pill extraction.

I think your answer to my second question clarified things for me. The first reduction will happen no matter what, but I now understand that acidic conditions enable a second reduction on the hydroxyl group...

I think this looks very promising, and hope to meet Someone Who Isn't Me in the next few months who will try this!

--aia

ChemoSabe
(Hive Addict)
06-25-04 08:31
No 515340




Glad my comment proved useful
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Even though I've read and reread this thread ad infinitum it's still mostly over my head so I'm glad what I did write led you to a better understanding of your first Q.

All I can really say about it after a few more read-throughs is best of luck to you all working towards a one pot shot on this. You guys are blazing a very interesting trail.

Personally my intuitions lean towards something somehow incorporating Pd with all this but don't ask me why 'cuase I really don't know.

He was just another tree in the forest whom nobody heard on his final fall

aia2
(Stranger)
06-25-04 13:28
No 515385




possible byproducts?
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What's the NCH3 functional group on the imine called? I would guess from the name 2-(methylamino)-1-phenyl-1-propanol that it's a methylamine, but NHCH3 in ephedrine and methedrine is also called a methylamine right?

Anyhow, I am wondering about the possible byproducts of a reduction of this imine due to incomplete reduction in acidic conditions... might there be some that only gets its hydroxyl group reduced? Or would the double bond to NCH3 be the more attractive reduction target? I would also suspect that some imine would only be reduced to ephedrine as well.

If my first suspected byproduct is possible, what is it?

Thanks!

--aia

Organikum
(Wonderful Personality)
06-25-04 15:17
No 515397




If Adams catalyst, platinium oxide or a ...
(Rated as: good read)
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Imine is the name of the functional group. The compound is named xxxx-xxxx-imine. Same principle like with the amines.

If Adams catalyst, platinium oxide or a similar Pt/C catalyst in acidic conditions is used, then the imine comes first followed by the hydroxy group on the alpha carbon and next to come would be the aromatic ring itself.
The reduction of the imine and the hydroxy group "overlapp", the ringreduction needs more rigid conditions. To avoid ringreduction the amount of hydrogen taken up can be measured and the reaction terminated in time. Or it can be done CTH style.

But this requires quite sophisticated equipment and catalysts and very clean starting compounds.

If Al/Hg or Zn/Hg or Zn/HCl is used ringreduction wont be a problem AFAIK, but I doubt that the OH-group will be reduced like the imine, say you will have a mixture of ---- and ephedrine.

As in a plain reductive alkylation with Al/Hg and methylamine the raw extract from the biosynth can be used with very good yields it is IMHO better to do this in two steps. First l-PAC to ephedrine (or by using rougher conditions to a mixture of ---- and ephedrine) followed by one of the wellknown reactions to convert this to ---- exclusivly. d----- of course.
It should be not forgotten that the recrystallized product of the alkylation is un-gakked ephedrine which is not to compare to the pfed extracts from pills. Whoever remembers the old days will back this up.
Somebody who masters the biosynth and red. alkylation for sure will be able to produce HI without phosphorus and to recover the iodine after the reaction for reuse.

If one is able to produce l-PAC but finally lost his nerves on this (pseudo)ephedrine reduction thingie, like I did, he might take a look into Bandils most famous writeups and realize that l-PAC can be converted to norephedrine the same as it is converted to ephedrine.

But first: LEARN TO MAKE BENZALDEHYDE FROM OTC COMPOUNDS BEFORE TALKING ABOUT SHORTCUTS FOR l-PAC TO ----!
got this?

Schnabufugl!

aia2
(Stranger)
06-25-04 15:45
No 515402




benzaldehyde?
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Thanks for the naming help, and also going into the different catalysts for reduction.

If Al/Hg or Zn/Hg or Zn/HCl is used ringreduction wont be a problem AFAIK, but I doubt that the OH-group will be reduced like the imine, say you will have a mixture of ---- and ephedrine.

So if this mixture was used with a well known reaction, the ---- already there won't be endangered right? In that case the "l-PAC -> mumblemumble-imine -> ----+E -> ----" method might compensate for its additional step by increasing yield. It gets two opportunities to get to methedrine instead of one.

But first: LEARN TO MAKE BENZALDEHYDE FROM OTC COMPOUNDS BEFORE TALKING ABOUT SHORTCUTS FOR l-PAC TO ----!

Funny, I just got back from reading the reference in Wanted References Vol. 1 about oxidizing alcohols and ethers with hypochlorites, where they report 98% yield converting benzyl alcohol to benzaldehyde with both Calcium hypochlorite and Clorox.

However, since this is all theoretical for me for the foreseeable future, I don't really see why that's a prerequisite.

Organikum
(Wonderful Personality)
06-25-04 17:42
No 515433




HI reactions dont overreduce.
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HI reactions dont overreduce. Birch-style reactions with Li can well overreduce. Birch-style reactions with Na hardly do and those with K are told to do this never.

For this reason I named the HI reaction as a good one for transforming a mixture of ---- and ephedrine to ---- only.

If this is and stays all theory for you, the practical advise on the manufacture of benzaldehyde does not apply to yours and there is no need to complain about. I am actually posting here not only for you aia2, but for many others too - this is at least one of my most beloved illusions....

Schnabufugl!

jemma_jamerson
(Hive Addict)
06-25-04 19:28
No 515453




otc benzaldehyde->lpac->----
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forgive my ignorance, i cant find any thing in tfse, but orgy, if you go directly to BENZALDEHYDE, isnt it more practical to go straight to p2p them ----, practical meaning in yeild and ratio of precursor for BENZALDEHYDE to finalo product.

as opposed to using all your BENZALDEHYDE to make l-pac then ----?

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Vitus_Verdegast
(Hive Addict)
06-25-04 19:40
No 515455




that depends...
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...if you can obtain nitroethane or 2-chloropropionic acid esters, or if the 35% yield from the aldol condensation with MEK followed by peracid oxidation is acceptable for you.

...or more concrete, whether you prefer d-methedrine above dl-methedrine, or vice versa.

But, as organikum said before, better to concentrate first on the best way to oxidize cheap paint thinner (toluene) into benzaldehyde.

http://www.psychedelicrepublicans.com/

Rhodium
(Chief Bee)
07-08-04 15:20
No 518222




Yet another L-PAC to Ephedrine Amination
(Rated as: good read)
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N,N'-Dimethyl-1-phenyl-1,2-propanediamine. A Hither to Unreported Product in Ephedrine Synthesis
Seymour Hyden, Santo Emmanuele, Henry Wetstein, Godfrey Wilbert
J. Med. Chem. 10, 953-954 (1967) (https://www.rhodium.ws/pdf/ephedrine.l-pac.menh2.pdf)

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