Isomers and tartaric acid

[btcboss2022]

I think something wrong with graph.
If you use L+-tartaric acid(cheaper and easier to find)the D enantiomer(amph,Meth) will be in the solution not in the solid as there appears.
If you use D-tartaric acid(more expensive and difficult to find) the D enantiomer(amph,Meth) will be in the solid.
Thanks.

 

[G.Patton]

His scheme is correct. Salt is precipitated into the solid state. No difference, d-amphetamine l-tartaric acid salt or l-amphetamine d-tartaric salt. You can change acid and get difference isomer in the solid state with following procedures.

P.S. same for methamphetamine.

 

[Ihml]

I’m not Patton, but: it’d produce only D-meth of the ephedrine that was used was derived from a plant, since plants naturally only produce L-ephedrine (which turns into the opposite enantiomer after reaction - D-meth in this case). If chemically synthesized ephedrine was used, than you’d get racemic meth, because ephedrine synthesis isn’t stereospecific.

 

[btcboss2022]

Ok I have the results of my tests trying to follow the video method but the similar reagents that I have on hand and that I usually use.
I divided 70gr of racemic freebase(not steam distilled and no acid-base washing made just extracted and dried from the NaBH4 P2P reduction) in 2 equal parts of 35gr each. With the first 35 gr I did video process but with some different reagents and with the other 35gr I did the method that I use to make that is similar to the video process:

- Method 1(Video method)


- 35gr pure freebase
- 42gr L-tartaric
- 205ml Methanol
The amounts are like video ratio but methanol I decided to use a 12% less due ethanol in video is a 88% solution.
I added the acid to the flask later the methanol and finally the freebase.
Once I started stirring immediately happened what usually happened to me in the rest of the processes I have tried for this purpose the solid salts precipitated quickly forming a mass.
I reflux it during one hour, with heating the mass come a thick liquid.
After the refluxing hour I keep it at RT around 4-5 hours until no new solids are visible created in the mixture.
I filtered it and keep in different pots the solid and the liquid part.
-Liquid part
I get cold the liquid part in the freezer with a NaOH solution to avoid excess heat in the alkalinization step.
I added slowly the NaOH solution to the mixture until ph13 and add it to a separation funnel during 30 min.
I take out the aqueous bottom layer and keep it , the thin oil top layer is kept in a pot.
I extract with DCM the aqueous layer and add these DCM extractions to oil layer.
I dried it with anhydrous sodium sulfate and filtered it.
I evaporated the DCM and 10gr of D-meth freebase obtained(don't looks as clean as it should)
- Solid part
I added more or less the same ml of warm water than gr of the solids weight, they has been dissolved it with stirring and let it cool down.
I added slowly the cold NaOH solution until ph13 and add it to a separation funnel during 30 min.
The next steps are exactly the same as the liquid part process.
After DCM is evaporated I got 15gr of L-meth freebase quite "dirty" too

- Method 2(the one I usually do and similar to the video method)


- 35gr pure freebase
- 41,2gr L-tartaric
- 412ml Methanol
Methanol and tartaric are mixed until complete dissolution, freebase is added while stirring and continue stirring vigorously 2-3min.
Let it at RT during 24 hours until the complete solid mass is formed(if in a couple of hours no solids are formed you should stir it again)
It's filtered and now are exactly the same steps as the other method.

- In the liquid part once I had all the DCM extractions I decided to make an acid-base washing, even the DCM color looks cleaner than the other one, to avoid to be "dirty" like the first method happened and I obtained 10gr of D-meth absolutely clean and pure(pic link at the bottom)
- In the solid part 13gr of enough clean L-meth freebase without acid-base washing obtained.
- Cleaning issue could be fixed during the crystallization stage too are many ways.

Obviously is very difficult to check how much D or L are in reality in the stuff only with Chiral analysis not easy accessible.
I also know that it is not the most correct to compare two methods using some different reagents but in reality they do practically the same function in the process.

In short, similar methods and yields the main differences are that in the second one you can avoid the reflux(so could be easier) and the final freebases looks cleaner than the others method.

When I will have free time again like this weekend(unfortunately not usual :-( only will be remaining to test in small scale the"mexican"method for meth isomer separation is quite different and I only did it in big scale although I finally decided to use the method explained for big scale too.
These would be the 3 methods that I did and I can talk about them with experience.

About when and how to make an acid-base washing instead steam distillation...etc etc needs a complete and long post the same for crystallization.

I'm thinking to post all the possible and more profitable options during the route from BMK(5449) to D-Meth HCL but this would be a long work and I don't know when I will have enough time again hahah at least is planned.

Thanks.

 

[jade52]

can anyone tell me what he meant "acid - base washing"?
@Osmosis Vanderwaal i know you are smart enough to enlighten a dumass

 

[Osmosis Vanderwaal]

I stayed up all night combing through scholar and patents and here is my findings

L(+) tartaric acid (2R,3R) is the naturally occuring isomer.Since it's chiraliity ir R,R, it bends light and is optically active. D(-)(2S,3S) is also optically active. These 2 compounds are enantiomers. They share the same boiling, freezing, temperature, mol.wt. ect.
The diastereomer of both is meso tartaric acid. (2R,3S or 2S,3R) the 2 mesos are enantiomers.
What makes a compound optically active is bending light. What make it bend light? Having an uneven plane of carbon substituants. For instance L(+)tartaric acid is active. It bends light right and right ( I say right but I am just using right as a reference). Same with D(-) tartaric acid, it bends light " left left". Meso tartaric acid is chiral but not optically active. Because (for instance) 2R,3s bends light right the left again for a net gain of 0°.
The reason we are talking about optically active compounds is because active compounds have a higher melting point and a higher boiling point. Another way to look at it is they solidify(crystallize) at a higher temperature. Yes an optically active compound crystallizes before an inactive one. Now we get to the point.
If you use D(ss) tartaric acid the D-(S) Methamphetamine is optically active (S,S,S) and the L(R) Methamphetamine is not, (R,R,S)
The opposite is also true. If you use the natural isomer of tartaric acid, the levo-methamphetamine crystallizes first, so if you use natural tartaric acid, the crystals are the trash. The rework. The mother liquor contains the Dextro-meth.
If you use racemic D,L-tartaric acid on racemic meth, you crystallize racemic Methamphetamine tartrate. Wasted your time.
Summary of the invention; use one tartaric acid isomer and if you want the D-crystals, use the D tartaric acid. Otherwise use the L and filter the crystals out.
Bring your references when you come to debate these facts.

 

[Labchef]

What you are saying is that D tartaric with salt out “L amph d tartrate” while L tartaric will salt out “D amph L tartrate”. Is that right

 

[Acab1312]

Very nicely explained, and I can agree with you 100%. I would like to add: Levo-methamphetamine tratrate is not soluble in cold methanol (Very low). Use it to flush the L-methamphetamine tratrate. After I started flushing, my final yield of d-methamphetamine increased by about 5%. What is also highly recommended is a polarimeter to measure chirality. If necessary, it can be built by yourself.

 

[Labchef]

A member with an expert status suggests using DL tartaric acid to separate both isomers I.e DL tartaric acid will salt out D amph/meth tartrate & dissolve the L amph/meth tartrate in the alcohol mother liquor. Do you think it’s possible to obtain D amph/meth using DL tartaric acid. For now I can only get the L tartaric acid. I hope to perform the resolution soon & obtain pure D meth.

 

[Acab1312]

For me, d,L tartaric acid did not work, L-tartaric acid is the most effective and cheapest to work.
There is also the possibility: via dibenzoyl tartaric acid, the chiral separation is highest in one pass, but also the highest in terms of price. But I have posted a synthesis for dibenzoyl tartaric acid

 

[Osmosis Vanderwaal]

Since then I learned that L tartaric won't bind to D meth because of steric hinderance and vice versa. I'm not sureif it's the same for amphetamine or not. If it is, then it's L-amp-L-tartrate od D-amp-D-tartrate because these are the optically active isomers. If you have 1L,2D or 1D,2L the net rotation is 0. Both chiral carbons have to turn the same way to be optically active .

 

[Labchef]

So I can’t use L tartaric to separate D & L and obtain pure D amph/meth is that what you are saying? Can DL tartaric acid be used for the same purpose.

 

[Osmosis Vanderwaal]

No, I didn't say that. You can L or D tartaric acid if you use L,you have L-meth L-tartrate, an acid salt ( and D-meth base. The salt will precipitate from non polar solvent and you filter it off and the reaction mixture still holds the D, that you can hcl ( hcl isn't chiral, so it obviously attaches to either). If you use D yartaric though A) it's a lot more expensive, 2) it's watched, VI) YOU'LL have to strip the tartrate of and hcl it

 

[Labchef]

Ok, that’s what I actually thought. The video seems to confuse people because DL was used for the resolution. Thanks for the clarification

 

[VamonosPest2]

is it possible to save the L-amphetamine somehow?

 

[Osmosis Vanderwaal]

You say save it, like it's dieing. You recover it, wether you want to or not. Now the question I think you are really asking is "Can a person turn L-meth into D-meth?" and the answer is yes, via several pathways, racemerization epimerization and SN2 inversion.