Isomers and tartaric acid

[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.

 

[btcboss2022]

This is the way how isomer separation looks like after 1 hour with method 2 ;-)

 

[Acab1312]

Hello btcboss2022 I tested their method, unfortunately it didn't work for me. Everything worked out wonderfully with the precipitation. Unfortunately, with the separation of the freebase from methanol I did you something wrong, could you explain the separation of the liquid phase again in how far you separate it?

 

[btcboss2022]

Is not my method hahah but ok I understood you, what you did exactly and what happened?

 

[Acab1312]

I set the methanol/freebase mixture to ph 13, and tried to extract it with toluene, but everything mixed. Because of that, I couldn't separate it. How do you do that, or where is my mistake? Regularly I did it with h2o, quite similar to this method. The only annoying thing is that I have to disconnect 2x to get a high d-isomer and thus get high losses.

 

[btcboss2022]

How you set it until ph13?
If sodium hydroxide water solution used is impossible that its get mixed with toluene you must have 2 layers.
If any alkali methanol solution used you just need to evaporate methanol not extract. Possibly solid precipitation happened is that last case you should filter it dissolve that solid in water and extract with solvent.

 

[btcboss2022]

If you have all mixed in one layer I guess you used an alkali methanol solution to set it to ph13.
In that case you must fix it adding water until 2 layers appears.

 

[Acab1312]

That's how I did it, thank you very much

 

[btcboss2022]

Once 2 layers appears you must take the toluene layer and evaporated but in that case you should evaporate the methanol from the other layer and later extract again possibly some freebase is remaining in the methanol.

 

[Acab1312]

Thanks: I will do so, and give an update when my polarimeter arrives on the exact ee-value

 

[btcboss2022]

I dont speak German sorry

 

[Acab1312]

I will do it this way, and give an update when my polarimeter has arrived, about the exact ee value.

 

[Jordan Belfort]

Brother, use hexane.

Hexane layers with methanol and water.
Toluene layers with water but NOT with methanol

https://www.sigmaaldrich.com/MK/en/technical-documents/technical-article/analytical-chemistry/purification/solvent-miscibility-table

 

[Acab1312]

Thank you

 

[ZACARIASKLK123]

@btcboss2022

Even though some people are not thankful towards you, I am. Thank you for sharing your report

 

[Mr Good Cat]

Could someone describe some basic principles of tartaric acid for the newbies, please? Or, might be, there is some popular article about it?

I read some "leaflet" about tartaric acid, and got the impression it reacts separately with one isomer only (LorD) leaving another one intact. Is it wrong?

Of course, I can repeat the steps as described in the "manual" without understanding, but my state of mind always demands to fully understand the topic.

 

[Never to sleep]

Very simple.

To a solution containing your racemic mixture of choice is added L-tartaric acid until no more precipitate forms. The precipitate is the levo isomer.

If that's what you wanted you filter it, the filter cake is your product (a tartrate salt).

If you want the dextro isomer it remains dissolved in the filtrate instead of the filter cake. Then you convert it to the desired salt like for instance a hydrochloride by pumping HCl gas through the solution. There are usually mane stable salts which you can precipitate from the filtrate afterwards. Depends on which one you want.

To note though you can also buy D-tartaric acid but it is more expensive and generally not worth it.

The general idea is that since the acid is either (L-) or (D-) it will always react only with the specific isomer of the two enantiomers.

 

[Mr Good Cat]

Thanks. This is exactly what I wanted to know.

I asked as I read a few methods here, on BB, and all of them refer to proportions 1:1.1-1.2 of FB to the acid. And this is quite weird for me, as technically 1:0.5 will be enough. I guess extra acid is added to reduce solubility of methanol or water.

If I'm right, then probably we can do something different:

1. We are looking for R-isomer of meth. So we acidify the FB with D-tartaric in proportions 1:0.5, then add petroleum ether and separate FB with R-isomer without waiting for salt percipitation, as classical abe.


2. We are looking for S-isomer of MDMA. So we acidify the FB with L-tartaric in proportions 1:0.5, then add petroleum ether and separate FB with S-isomer...


3. We are looking for S:R isomers of MDMA in proportions 2:1. So we acidify the FB with L-tartaric in proportions 1:0.25, then add petroleum ether and separate FB with required mixture 2:1...

Am I thinking in the right direction?

 

[Never to sleep]

It's important to remember that the term "racemic mixture" is broad.

You don't always as a rule obtain a 1:1 mixture of the isomers when utilizing something like P2P and definitely not ephedrine in case of which the ratio is more like (0.7-8) : (0.2-3) where there larger portion composes of the dextro isomer. Even if you use P2P you might obtain a mixture with more dextro than levo isomer but you still refer to it as racemic.

So it's not entirely accurate to assume that adding half the weight of your freebase of the acid is ideal. This is why you should observe the precipitation as it is happening to help you determine the amount to add rather than adding it blindly.

Even then you really can't overshoot it if you add more than ideal. The pH of the solution does not change much so long as the salt precipitates as a result of an acid-base reaction where the freebase is the base which neutralizes the acid. There is some wiggle room where you can add more than ideal just not too much. If you add it in small portions and monitor the precipitate adding one extra spoon which goes over the ideal amount is not a problem. Adding less than ideal is a problem though since provided you sell the product as dextromethamphetamine it is literally contaminated with a contaminant which was meant to specifically be removed.

Hope this helps. I must point out that when I was researching this myself back then I was in a similar headspace as you are. Really fucking confused by strangely varying information which was wildly inaccurate regarding this process. It really is as simple as I've described in the last comment. There is no secret to it.

 

[Mr Good Cat]

What if I try to go from another side?

For example, I'm targeting for MDMA S-isomer. I apply classical ABE with ether to mother liquor. So, I have the FB in ether.
Then, L-tartaric is soluble in ether as well, but the salt is not soluble. So I simply prepare another solution of L-tartaric in ether, and start dripping it slowly to avoid excess of heat, may be even using the ice bath.
I guess, the salt starts precipitate immediately as the FB reacts with L-tartaric (as salt is not soluble in ether). I continue dripping ether with L-tartaric until precipitation continues. Then separate ether with unreacted FB, evaporate ether and acidify it with HCl.
Sensitive point is the leftovers of unreacted L-tartaric that may left in the ether. Is it necessary to remove it and how?

 

[UWe9o12jkied91d]

Umm, no? If using L-tartric the precipitate is the good stuff

 

[UWe9o12jkied91d]

You are right, I see the procedure you are proposing as working.You could use anhydrous methanol or ethanol to dissolve your acid since I think is more soluble in these then diethyl ether.
Or just add solid and stir, even if the tartric is not soluble in ether it will precipitate you product which will appear as a flocculant in solution while the unreacted acid will sink to the bottom, it is fairly obvious to tell.

 

[Mr Good Cat]

No, no, no! It is common misunderstanding, we had a long discussion with @btcboss2022 about it.
For meth - yes, good stuff is R, and it will be in solids. But for MDMA it is vice versa: R is useles, S is desirable.

 

[Mr Good Cat]

Actually, I was thinking about petroleum ether. As I checked the properties in different sources, L-tartaric is soluble in pertoleum ether, but haven't found any details about percentage.
As I remember, petroleum ether is easily explosive. How excessive is heat release when FB acidified by L-tartaric?

 

[Jordan Belfort]

If that is the case, you would be able to extract it with hexane or toluene. But you can't

 

[Never to sleep]

Did you even actually try to perform this yourself? You know that there is no way D-methamphetamine tartrate precipitates when you add L-tartaric acid right? The acid which is the L- isomer only reacts with the same isomer of an opposite base. Meaning it is exactly like I said. Your desired D-methamphetamine (the better isomer of the two you would wanna keep) stays dissolved in the freebase which is the liquid filtrate which you can then directly pump with dry HCl gas to obtain the sweet D-methamphetamine hydrochloride salt. Trust me man. This is how it goes... Thank me later once you try out the result.

This truly does seem to confuse the shit out people.