L-Ephedrine synthesis from L-phenylacetylcarbinol (L-PAC)

[btcboss2022]

Any option to replace the microwave by normal heating obviously changing temp and time?

 

[btcboss2022]

@G.Patton Won't be enough with a standard reductive amination of the L-PAC?
Ethanol + methylamine (40% in water) + L-PAC and left to react at room temperature for 30 min, to allow imine formation.
The mixture was cooled to around 0 C and reduced using NaBH4.
The mixture was then basified and extracted with DCM
Dried dried anhydrous sodium sulphate, filtered and evaporated.

 

[OrgUnikum]

l-PAC is very sensitive to bases, they cause it to racemise what would be a pity. Acidic or neutral conditions are advised, with NaBH4 one can use use easily prepared derivates like STAB (from NaBH4 in Toluene with 3 equivalent GAA added) or Zinc-Borohydride (from anhydrous ZnCl2 and NaBH4) or others. No heating whatsoever is needed and water is no problem just add equimolar methylamine acetate to the l-PAC in Toluene add 0,01 molar tosic acid dihydrate and let it sit at rt for a day, this forms a stable Imine which is then reduced by STAB. Excellent yields. Avoids completely alkaline conditions. Only drawback is the amount of GAA needed - 4 equivalent

 

[The-Hive]

@Consider look here

 

[rampage]

my first trial run of making l-pac, here is my recipe not sure if it's all correct but i'll give it a go anyway.

2.5 ltrs of h2o
87.50 gms of molasses
yeast and nutrient
20ml of benzaldehyde
75ml of ether

in to a 5ltr demijohn goes 2.5ltrs of h2o and 87.50 gms of molasses,
saturate wash with pure oxygen,
add yeast and nutrient and allow to ferment for 8hrs or so,
once wash is rapidly fermenting add 10ml of benzaldehyde ,
after 4hrs or so add another 10ml of benzaldehyde and allow to ferment for another 12hrs or more,
once finished remove yeast,
extract l-pac with 50ml of ether and then 25ml of ether,
combine ether and distill
collect l-pac?
theoretical yield 10ml is 50% conversion.

feedback is appreciated and i'll post my results once done.

 

[OrgUnikum]

It seems not to be understood that this is a condensation reaction of two aldehydes. Benzaldehyde and - what? So Acetaldehyde is added and there is your second one. Or Acetone in the Austrian Patent which Uncle Fester sold (it does not really work like most of his stuff). Or Pyruvate is added this is a energy source for the yeast and forms Acetaldehyde in the process.

So, if you do this without a second Aldehyde or a precursor of it then TWO Benzaldehyde will be needed as Benzaldehyde + Benzaldehyde works too but of course maximum yield counted from Benzaldehyde is reduced to half.

And Dextrose and Frucose can provide energy but no Aldehyde to the reaction.

 

[OrgUnikum]

Sodium Pyruvate is the gold standard. Calcium Pyruvate works too. Problem is you need a frigging lot of it so for serious production Acetaldehyde is better suited. If you can buy Paraldehyde - thats perfect, easily de-polymerized to Acetaldehyde and far better to handle.
With Acetaldehyde you need to add a energy source like sucrose or dextrose though.
The trick with pyruvate is that it does not need the yeast fermenting.

 

[rampage]

how much sodium pyruvate would be required?

 

[rampage]

sorry guys this evaluation was not correct, there is a need to incorporate sodium pyruvate and a yeast strain that can handle slightly acidic conditions, ph 5 - 5.5, and possibly a greating temperature range. its still a work in progress, albite very slow progress lol

 

[rampage]

these are the questions i have:

ph of h2o, slightly acidic at 5 -5.5?
do i saturate wash with pure oxygen for yeast growth ?
is benz per ltr of h2o 4ml?
do i add additional benz of 4ml a ltr of h2o after 4hrs?
is ethanol production 35gms a ltr of h2o?
is ph 6 at various stages of benz concentration?
do i maintain 20 degrees celsius for wash?
Is there a need to change ph of solution before extraction??? if l-pac is sensitive to basing?
do i dry the ether/l-pac solution with anhydrous sodium sulfate or anhydrous magnesium sulfate before distilling?
is theoretical yield 50% or more or less?
molasses vs dextrose?

 

[handle]

Yes this synthesis has more questions than time..

 

[handle]

Have you made any progress?

 

[handle]

10 mM of benzaldehyde is approximately 1.0612 g/L. This concentration would be used to optimize L-PAC production.

 

[Consider]

Please who will teach me by hand on how to make l-ephedrine, I am willing to pay for the knowledge

 

[rampage]

hi consider, you need to do most of the study ones self then through trial and error put things into practice, document any trial then you will have the questions you need to obtain the proper answers, good luck

 

[The-Hive]

Don’t buy it I have over 1000 messages on 11 syntheses and he could stick to one complicated the whole process by switching synthesis

 

[Consider]

Rampage please I appreciate you work with me but u taught me to do P2P which gave racemic and I just hate everything about racemic, secondly u taught me another process which yielded nor - ephedrine which could not be used to produce meth, I don't like argument and say thank you dear, I made my mind that i want to learn l-ephedrine or D-pseudoephedrine, that i can use for meth production, dear if anybody can help me in this area I will pay you thousands of dollar

 

[Consider]

Rampage please I appreciate you work with me but u taught me to do P2P which gave racemic and I just hate everything about racemic, secondly u taught me another process which yielded nor - ephedrine which could not be used to produce meth, I don't like argument and say thank you dear, I made my mind that i want to learn l-ephedrine or D-pseudoephedrine, that i can use for meth production, dear if anybody can help me in this area I will pay you thousands of dollars

 

[Consider]

Hive I just don't like racemic stuff which you taught me, I finally made up my mind to learn how I can produce L-ephedrine or D-pseudoephedrine from yeast fermentation or any other method with good yield that would not lead to racemic product, am willing to pay thousands of dollar to my mentor, am confident that an expert is here that has the knowledge, please let's do business

 

[handle]

No point making l-pac. Yield 0.5ml l-pac per 1L of water. Makes No sense. 20L of water for 10ml of product? Mmm?

 

[rampage]

hi handle
may i ask how you worked that out?

 

[handle]

Biotransformation for L-Ephedrine Production
P.L. Rogers, H.S. Shin and B. Wang. Department of Biotechnology, University of New South
Wales, Sydney 2052, Australia

Spoiler: Benzaldehyde Concentration

2.3 Benzaldehyde Concentration
The effect of benzaldehyde on L-PAC production by S.cerevisiae has been investigated by Gupta
et al. (32) and Agarwal et al. (33). The latter authors reported that once the benzaldehyde
concentration increased above 16 mM (1.7 g L-1), the species rate of L-PAC production
decreased, and beyond 20 mM (2.1 g L-1) it was inhibited completely. When the residual
benzaldehyde declined below 4 mM (0.4 g L-1), the formation of benzyl alcohol was predominant
over L-PAC. They estimated that the optimum benzaldehyde concentration range
was 4-16 mM. Further studies (34) cited the optimum concentration for L-PAC
production as 10 mM (1.1 g L-1).

 

[rampage]

interesting org, how would you go about doing a continuous extraction?

 

[OrgUnikum]

I would start using a bloody internet search engine

 

[Consider]

Please how do I separate DL-Pseudoephedrine to have only D-pseudoephedrine

 

[handle]

Using d-tartaric acid as a resolving agent.
Extraction of d-amphetamine
Scroll down to around pic17 I think.

 

[The-Hive]

He’s just Contradicted himself