From L-meth to D-meth

[Selassi]

Hello guys,

Maybe a noobquestion but is there a route or pathway to convert the L-meth-isomer into the D-isomer?
I mean after u seperate the racemic mixture with tartaric acid what are the options with the L-stereoisomer?

 

[G.Patton]

I mean after u seperate the racemic mixture with tartaric acid what are the options with the L-stereoisomer?

SelassiWhat do you mean "options"?

Maybe a noobquestion but is there a route or pathway to convert the L-meth-isomer into the D-isomer?

You can do same procedure with meth as described here for amph.

 

[Selassi]

What do you mean "options"?

You can do same procedure with meth as described here for amph.

G.PattonYes i know how to seperate the racemate into D and L.

I meant after the seperation of the racemate, its possible to convert the L into the D isomer?

Only the D-isomer is sold then as meth, so what do the big producers do with the L-isomer? Thats what i meant with " options"

 

[G.Patton]

I meant after the seperation of the racemate, its possible to convert the L into the D isomer?

Selassino

Only the D-isomer is sold then as meth, so what do the big producers do with the L-isomer? Thats what i meant with " options"

They sell it as D-isomer as well, or sell as racemate.

 

[Selassi]

I know its theoretically possible to do this optical inversion.
Ill take a dive into this matter and keep everybody updated

 

[MadHatter]

Just a question: what would happen if you converted the L-methamphetamine to amphetamine? You'd get L-amphetamine right? Which isn't totally useless.

 

[sharetea]

once you have seperated the d and l..
the process is cslled racemitatuon..

which then conveets your l meth back into racetize mixture... of l/d again..
you resolve and repeat the process..


RRR racemitization resolution and i thinm last ris recycle

 

[41Dxflatline]

Hello guys,

Maybe a noobquestion but is there a route or pathway to convert the L-meth-isomer into the D-isomer?
I mean after u seperate the racemic mixture with tartaric acid what are the options with the L-stereoisomer?

SelassiS Patent 2797243

Improved Method for Converting l-Amphetamine into d-l-Amphetamine


This invention relates to an improved method for obtaining greater yields of a desired optically active isomer from racemic mixtures and more particularly to a method wherein optically active isomers are converted to the corresponding optically inactive racemic mixtures.

Example 1:

A mixture of 50g of l-amphetamine and 5g of Raney nickel was charged into a Magne-Dash autoclave and the bomb pressurized with hydrogen to an initial pressure of 100lbs. The mixture was stirred and heated at 95-100*C for 5 hours, after which time the reaction was cooled and the nickel removed by filtration. The treated base showed a rotation of –3.1*. This would amount to about 65% racemization of the l-base present initially.

Example 2:

A mixture of 135g of l-amphetamine, 50g of Raney nickel and 1.7g of ammonia gas in 10cc of methanol was charged into Magne-Dash bomb and pressurized to 100lbs with hydrogen. Then the mixture was heated to 150*C and maintained at this temperature with stirring for 19 hours. The reaction was then cooled, the gases vented, and the reaction mixture filtered to remove nickel catalyst. A 50g aliquot was distilled yielding 37.4g (75%) of amphetamine; BP: 83-87*C/15mmHg, and 4.8g of residue consisting of diamine. The rotation of the essentially d-l-amphetamine was –0.3*.

Example 3:

A mixture of 135g of l-amphetamine, 50g of Raney nickel and 0.5g of ammonia gas in 10cc of methanol, was charged into a Magne-Dash autoclave and pressurized to an initial pressure of 100lbs of hydrogen. The reaction was heated at 150*C with stirring for 13.5 hours. The gases were vented from the cooled reaction vessel, and the mixture filtered to remove catalyst. A 50g aliquot sample was distilled under reduced pressure to yield 37.4g of amphetamine; BP: 83-86*C/15mmHg., and a residue of diamine weighing 10.4g. The yield of amphetamine was 74.5%, and the rotation of essentially d-l-amphetamine was –0.2*.

Example 7:

35.5g of l-amphetamine was charged into a Magne-Dash bomb containing used Raney nickel catalyst. This mixture was cooled in ice, and treated with a cold solution of 2.2g of ammonia gas and 10cc of methanol. This mixture was then shaken in an atmosphere of hydrogen (initial pressure 100lbs) and at 150-155*C for 10 hours. During this heating period a pressure of 250 lbs was developed. The bomb was cooled, the nickel catalyst allowed to settle and the base poured out by decantation. The solvent methanol was removed by distillation in vacuo and the residual oil fractionated. BP: 82-86*C/15mmHg., The yield was 30g (85%) no forerun and only a small amount of still residue. The rotation was –2.4*.

Other examples were available but at lower yields and lesser racemization.

 

[Amphibian]

from the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA):

Recycling unwanted by-product: a game-changer in methamphetamine production​

Previously, when the d-methamphetamine was separated using tartaric acid, the leftover material containing the l-isomer was regarded as an unwanted by-product to be discarded. Illustrating the continuous drive to improve efficiency and profits, illicit drug producers in Europe have introduced new methods to reconvert these discarded solutions back to a racemic 50:50 mixture of d- and l-methamphetamine, from which the d-methamphetamine can be separated using tartaric acid. These recycling procedures explain the record quantities of tartaric acid seized in Europe (see Figure Quantity of tartaric acid seized in Europe).

This process can be repeated several times: each time a fraction with the unwanted l-methamphetamine is produced, it can be reconverted (‘racemised’) back to a mixture and the d-isomer separated until the waste cannot be further recycled. The process, called ‘RRR’ (resolution-racemisation-recycling) (see Figure Processing of methamphetamine: resolution-racemisation-recycling), is a standard technique used in the pharmaceutical industry to increase production yields of medicines where only one isomer is pharmaceutically active (Astleford and Weigel, 1997). The RRR technique increases the yield of d-methamphetamine from BMK from 50 % to 75 % after one iteration, up to 87.5 % on the second iteration and 93.75 % by the third. The racemisation of the discarded solutions of l-methamphetamine is triggered using small amounts of a chemical such as AIBN (or another radical initiator) and a source of thiyl radicals (for example methyl thioglycolate, thioglycolic acid or dimyristyl peroxydicarbonate) (Escoubet et al., 2006; Yerande et al., 2014). AIBN has a low decomposition temperature, can easily ignite and its use presents a risk of explosion (National Center for Biotechnology Information, 2022).

Data reported to the European Commission indicates that in 2020, 327 kilograms of AIBN, 525 kilograms of methyl thioglycolate, 248 kilograms of dimyristyl peroxydicarbonate and 2.5 litres of thioglycolic acid were seized in Europe. Partial data available for 2021 indicate seizures of 19 kilograms of AIBN, 90 kilograms of methyl thioglycolate, 139 kilograms of dimyristyl peroxydicarbonate and 20 litres of thioglycolic acid. All seizures occurred in the Netherlands and some were seized during the dismantling of illicit laboratories. Information reported by Dutch police to the EMCDDA indicates that at least one shipment of 13 kilograms of AIBN in 2021 originated in Mexico. As well as indicating the level of sophistication involved, bearing in mind that these reagents are required in small amounts (relative to the quantity of methamphetamine being treated), the quantities seized provide further evidence of the scale of methamphetamine production using BMK methods in Europe. They also show that combining the expertise of Mexican and Dutch drug producers and applying techniques from the pharmaceutical industry has maximised production efficiency....

Source: https://www.emcdda.europa.eu/publications/eu-drug-markets/methamphetamine/main-production-methods-europe_en

 

[SoldadoDeDrogas]

Can anyone help me understand if it is possible to use generic nasal inhalers that contain "levmetamfetamine 50mg" to get to d-meth.
https://bbgate.com/threads/methamphetamine-synthesis-vicks-inhaler.4974/#post-46343 Will these instructions work in theory?
Or do I need to use the above racemization and resolution provided by Amphibian? Or 41Dxflatline, etc?

 

[SoldadoDeDrogas]

Can anyone help me understand if it is possible to use generic nasal inhalers that contain "levmetamfetamine 50mg" to get to d-meth.
https://bbgate.com/threads/methamphetamine-synthesis-vicks-inhaler.4974/#post-46343 Will these instructions work in theory?
Or do I need to use the above racemization and resolution provided by Amphibian? Or 41Dxflatline, etc?

SoldadoDeDrogasI have answered my own question and it appears as though the RRR or simillar procedures will be necessary.

 

[azides]

Can anyone help me understand if it is possible to use generic nasal inhalers that contain "levmetamfetamine 50mg" to get to d-meth.
https://bbgate.com/threads/methamphetamine-synthesis-vicks-inhaler.4974/#post-46343 Will these instructions work in theory?
Or do I need to use the above racemization and resolution provided by Amphibian? Or 41Dxflatline, etc?

SoldadoDeDrogasWhile it would work... some of those chemicals are hard to get or might be dangerous like my username, instead you should use naproxen and use the pope-peachy with the NASID Naproxen. I have posted the full guide below

 

[SoldadoDeDrogas]

While it would work... some of those chemicals are hard to get or might be dangerous like my username, instead you should use naproxen and use the pope-peachy with the NASID Naproxen. I have posted the full guide below

azidesHey @azides Thank you for response and info. I just went through all of that and am still trying to digest the contents. I am not a chemist so I am just trying to get my head around it. Basically, what I am getting is, if we take levo-meth and add naproxen and heat, we can turn it into racemic? Or am I not understanding correctly?
I have to ask - if it is that simple, why is nobody talking about or doing this? Do you have a work up or any info about the procedure?

 

[riahisunak]

Hey @azides Thank you for response and info. I just went through all of that and am still trying to digest the contents. I am not a chemist so I am just trying to get my head around it. Basically, what I am getting is, if we take levo-meth and add naproxen and heat, we can turn it into racemic? Or am I not understanding correctly?
I have to ask - if it is that simple, why is nobody talking about or doing this? Do you have a work up or any info about the procedure?

SoldadoDeDrogasTry it , it might work lol

 

[SoldadoDeDrogas]

Try it , it might work lol

riahisunakI will definitely give it a shot. I am wondering if anyone has extracted the nasal inhalers containing "Levomefamfetamin 50mg" - what is the best process for doing this and does it crystallize like ice will? Or what can I expect the isolated product to look like?

 

[azides]

Naproxen don't seems to be the best resolving agent:

https://www.designer-drug.com/pte/12.162.180.114/dcd/pdf/meth.chiral-sep.distn.pdf

btcboss2022Never said it was I said it was most accessible and better then plain tartaric acid

 

[btcboss2022]

Never said it was I said it was most accessible and better then plain tartaric acid

azidesI understood that was better for resolution and that only heating the L-meth obtained from this resolution it cames racemic Im sorry if I was wrong.

 

[btcboss2022]

Hello guys,

Maybe a noobquestion but is there a route or pathway to convert the L-meth-isomer into the D-isomer?
I mean after u seperate the racemic mixture with tartaric acid what are the options with the L-stereoisomer?

SelassiIm very very close to achieve it!!!!;-)

 

[riahisunak]

Im very very close to achieve it!!!!;-)

btcboss2022Are you going to post it brother

 

[azides]

Are you going to post it brother

riahisunakThru that way... or my easier I posted below props if you went thru all that hassle XD

 

[azides]

What the fuck is this crap? This is BBgate/ the new hive.. AIBN, methyl thioglycolate, dimyristyl peroxydicarbonate thioglycolic acid? Can anyone get these easily or cheap? Is it safe for the avg chemist?

Shit just googling DIMYRISTYL PEROXYDICARBONATE decomposes violently or explosively at temperatures 0-10°C owing to self-accelerating exothermic decomposition; Several explosions doesn't sound very ummmm unsafe for the avg chemist that would read this board. Hell it kinda reminds of this this guys username. And while meth chemists have been using AIBN to racemate meth on a bulk scale with D tartaric acid.

Clandestine chemists have also used NAPROXEN ages ago to convert the L into the racemate with heat. ... yes yes the NASID. This actually has a 2 fold advantage besides being safe, so really 3, 4 if count count it is accessible as all hell . The route is called a pope-peachy and i'll document everything for ya it really is as simple as it sounds

The trick is to find the cheapest optically active acid that will bind to one isomer but not the other and which will change solubility sufficiently so that one of the products (be it the unreacted freebase or the reacted amide, sulfonate or whatever) can be washed into another solvent (one that is immiscible with the first solvent) so you end up with one isomer dissolved in the first solvent, the other isomer dissolved in the second solvent.

Then the cool twist the meth makers use - the use of AIBN (which you all head by now) which will react with the secondary amine (via in imine) so that 50% of the less active/inactive isomer is transformed into the active isomer).
Below are examples of the class of racemization specified in the above paper. AIBN (azabisisobutyrlonitrile) is a catalyst for the radical reaction
https://www.academia.edu/81633940/T...Racemization_of_Nonactivated_Aliphatic_Amines


However this naproxen research it was based on... nothing new just old stuff but put 2 and 2 and bingo was his nameo the ideal Pope-Peachy. This resolution may have practical application because the efficiency of the resolution is in the same range as with tartaric acid but only 0.25 molar equivalent of resolving agent is required for the resolution of 1 mol base. Chirality 11:373–375, 1999. © 1999 Wiley-Liss, Inc.


Anyways PROFF it works on meth ohh IDK maybe this
Study of the mechanism of the optical resolution of N-methylamphetamine via diastereoisomeric salt formation by the Pope-Peachey resolution method as discussed by the retort later

https://sci-hub.wf/10.1016/s0957-4166(00)86170-4

https://www.sciencedirect.com/science/article/abs/pii/S0957416600861704

However ... instead of AIBN we use naproxen to turn l into racemic with heat . .Probably based on this retort I also found.. The same Pope-Peachy mentioned earlier .

As I said earlier...if the trick is to find the cheapest optically active acid that will bind to one isomer but not the other and which will change solubility sufficiently so that one of the products (be it the unreacted freebase or the reacted amide, sulfonate or whatever) can be washed into another solvent (one that is immiscible with the first solvent) so you end up with one isomer dissolved in the first solvent, the other isomer dissolved in the second solvent.

http://www1.udel.edu/chem/sametz/Sa..._Diastereomeric_Salt_Formation__Naproxen.html

The scheme https://dump.li/image/ac34d7b4b88983a0.jpeg

The Retort

Resolution of Enantiomers via Diastereomeric Salt Formation: Naproxen

In my biochem slides from CHE322 the analgesic naproxen is resolved in a manner very similar to that discussed in CHE321. Naproxen is a chiral carboxylic acid, and it is the (d)-(S)- enantiomer that is sold as the active drug.
Racemic naproxen is resolved by a modification of the salt-formation technique we learned in class. There are two twists to the protocol that make the process even more useful for commercial production of enantiomerically pure naproxen. First, in a twist known as the Pope-Peachy method, only half an equivalent of chiral amine is used. Half an equivalent of a cheaper, optically inactive amine base is used in its place. This not only makes the process cheaper, but results in a more dramatic difference in solubilities. The conjugate base of the desired (d)-(+)-enantiomer crystallizes out with the conjugate acid of the chiral amine, with high selectivity. This leaves the more soluble salt product of (l)-(-)-naproxen and the achiral amine behind in solution.
The second twist is that, by simply heating the “mother liquor” (the solution that remains after filtration) , the undesired enantiomer of naproxen can be converted back to a racemate. You will learn in CHE322 that protons next to a carbonyl are modestly acidic; this means that if you have a methine stereocenter next to a carbonyl you always have to be wary that its configuration can get “scrambled” by deprotonation/reprotonation. In this case, however, we want the configuration to equilibrate back to a racemic mixture, and the achiral base that was used, plus heat, is enough to do the job.
This process allows naproxen to be synthesized by a simpler, cheaper route as a racemate instead of a single enantiomer. Not only can the two enantiomers be resolved by this process, but the “undesired” enantiomer is converted to the desired, rather than being discarded--effectively doubling the yield of product.
Reference: Harrington, P.J.; Lodewijk, E. “Twenty Years of Naproxen Technology”. Organic Process Research and Development, 1997, 1, 72-76.
Or this Non-enzymatic dynamic kinetic resolution of racemic α-arylalkanoic acids: an advanced asymmetric synthesis of chiral nonsteroidal anti-inflammatory drugs (NSAIDs)
An efficient protocol was developed to produce chiral 2-arylalkanoic esters in high yields (up to 99%) from racemic carboxylic acids utilizing the racemization of the mixed-anhydrides generated from acid components with pivalic anhydride in the presence of an acyl-transfer catalyst. The present DKR involves the enantio-discriminating esterification of the racemic 2-arylalkanoic acids and the rapid racemization of the chiral 2-arylalkanoic acids under suitable reaction conditions using pivalic anhydride, diisopropylethylamine, and benzotetramisole (BTM) in a polar solvent, and this method was successfully applied for the preparation of pharmacodynamically active (S)-enantiomers of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen.

https://pubs.rsc.org/en/content/articlelanding/2012/cy/c2cy20329d

https://doi.org/10.1039/C2CY20329D


Someone told me they use naproxen but couldn't find anything... so I did some digging.

 

[btcboss2022]

What the fuck is this crap? This is BBgate/ the new hive.. AIBN, methyl thioglycolate, dimyristyl peroxydicarbonate thioglycolic acid? Can anyone get these easily or cheap? Is it safe for the avg chemist?

Shit just googling DIMYRISTYL PEROXYDICARBONATE decomposes violently or explosively at temperatures 0-10°C owing to self-accelerating exothermic decomposition; Several explosions doesn't sound very ummmm unsafe for the avg chemist that would read this board. Hell it kinda reminds of this this guys username. And while meth chemists have been using AIBN to racemate meth on a bulk scale with D tartaric acid.

Clandestine chemists have also used NAPROXEN ages ago to convert the L into the racemate with heat. ... yes yes the NASID. This actually has a 2 fold advantage besides being safe, so really 3, 4 if count count it is accessible as all hell . The route is called a pope-peachy and i'll document everything for ya it really is as simple as it sounds

The trick is to find the cheapest optically active acid that will bind to one isomer but not the other and which will change solubility sufficiently so that one of the products (be it the unreacted freebase or the reacted amide, sulfonate or whatever) can be washed into another solvent (one that is immiscible with the first solvent) so you end up with one isomer dissolved in the first solvent, the other isomer dissolved in the second solvent.

Then the cool twist the meth makers use - the use of AIBN (which you all head by now) which will react with the secondary amine (via in imine) so that 50% of the less active/inactive isomer is transformed into the active isomer).
Below are examples of the class of racemization specified in the above paper. AIBN (azabisisobutyrlonitrile) is a catalyst for the radical reaction
https://www.academia.edu/81633940/T...Racemization_of_Nonactivated_Aliphatic_Amines


However this naproxen research it was based on... nothing new just old stuff but put 2 and 2 and bingo was his nameo the ideal Pope-Peachy. This resolution may have practical application because the efficiency of the resolution is in the same range as with tartaric acid but only 0.25 molar equivalent of resolving agent is required for the resolution of 1 mol base. Chirality 11:373–375, 1999. © 1999 Wiley-Liss, Inc.


Anyways PROFF it works on meth ohh IDK maybe this
Study of the mechanism of the optical resolution of N-methylamphetamine via diastereoisomeric salt formation by the Pope-Peachey resolution method as discussed by the retort later

https://sci-hub.wf/10.1016/s0957-4166(00)86170-4

https://www.sciencedirect.com/science/article/abs/pii/S0957416600861704

However ... instead of AIBN we use naproxen to turn l into racemic with heat . .Probably based on this retort I also found.. The same Pope-Peachy mentioned earlier .

As I said earlier...if the trick is to find the cheapest optically active acid that will bind to one isomer but not the other and which will change solubility sufficiently so that one of the products (be it the unreacted freebase or the reacted amide, sulfonate or whatever) can be washed into another solvent (one that is immiscible with the first solvent) so you end up with one isomer dissolved in the first solvent, the other isomer dissolved in the second solvent.

http://www1.udel.edu/chem/sametz/Sa..._Diastereomeric_Salt_Formation__Naproxen.html

The scheme https://dump.li/image/ac34d7b4b88983a0.jpeg

The Retort

Resolution of Enantiomers via Diastereomeric Salt Formation: Naproxen

In my biochem slides from CHE322 the analgesic naproxen is resolved in a manner very similar to that discussed in CHE321. Naproxen is a chiral carboxylic acid, and it is the (d)-(S)- enantiomer that is sold as the active drug.
Racemic naproxen is resolved by a modification of the salt-formation technique we learned in class. There are two twists to the protocol that make the process even more useful for commercial production of enantiomerically pure naproxen. First, in a twist known as the Pope-Peachy method, only half an equivalent of chiral amine is used. Half an equivalent of a cheaper, optically inactive amine base is used in its place. This not only makes the process cheaper, but results in a more dramatic difference in solubilities. The conjugate base of the desired (d)-(+)-enantiomer crystallizes out with the conjugate acid of the chiral amine, with high selectivity. This leaves the more soluble salt product of (l)-(-)-naproxen and the achiral amine behind in solution.
The second twist is that, by simply heating the “mother liquor” (the solution that remains after filtration) , the undesired enantiomer of naproxen can be converted back to a racemate. You will learn in CHE322 that protons next to a carbonyl are modestly acidic; this means that if you have a methine stereocenter next to a carbonyl you always have to be wary that its configuration can get “scrambled” by deprotonation/reprotonation. In this case, however, we want the configuration to equilibrate back to a racemic mixture, and the achiral base that was used, plus heat, is enough to do the job.
This process allows naproxen to be synthesized by a simpler, cheaper route as a racemate instead of a single enantiomer. Not only can the two enantiomers be resolved by this process, but the “undesired” enantiomer is converted to the desired, rather than being discarded--effectively doubling the yield of product.
Reference: Harrington, P.J.; Lodewijk, E. “Twenty Years of Naproxen Technology”. Organic Process Research and Development, 1997, 1, 72-76.
Or this Non-enzymatic dynamic kinetic resolution of racemic α-arylalkanoic acids: an advanced asymmetric synthesis of chiral nonsteroidal anti-inflammatory drugs (NSAIDs)
An efficient protocol was developed to produce chiral 2-arylalkanoic esters in high yields (up to 99%) from racemic carboxylic acids utilizing the racemization of the mixed-anhydrides generated from acid components with pivalic anhydride in the presence of an acyl-transfer catalyst. The present DKR involves the enantio-discriminating esterification of the racemic 2-arylalkanoic acids and the rapid racemization of the chiral 2-arylalkanoic acids under suitable reaction conditions using pivalic anhydride, diisopropylethylamine, and benzotetramisole (BTM) in a polar solvent, and this method was successfully applied for the preparation of pharmacodynamically active (S)-enantiomers of nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and naproxen.

https://pubs.rsc.org/en/content/articlelanding/2012/cy/c2cy20329d

https://doi.org/10.1039/C2CY20329D


Someone told me they use naproxen but couldn't find anything... so I did some digging.

azidesThe way that im testing is not related with that products and processes, AIBN way is very difficult to scale up until I know only possible small scale and odor is one of the worst that exists.
In fact is more simple that all this anyway everyone can do what they want no problem.
About post it or not firstly I must achieve it completely and once that possibly will be offered as extra info to the guidance service customers.