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Author: Subject: Help! Questions concerning Extraction, Washing, and Concentration Every Hobby-Chemist Should Be Able to Answer!
Li Jun
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[*] posted on 30-6-2019 at 08:59
Help! Questions concerning Extraction, Washing, and Concentration Every Hobby-Chemist Should Be Able to Answer!


Hello, friends!

We, having no formal training in chemistry, followed the manufacturing instructions (patent) for an organic compound, let's call it "the goodies", which were published in a reputable chemical journal by a team of researchers with excellent credentials.

To our surprise, everything worked out for the most part on the first attempt. We really created the product we wanted, and, having carefully tested it over several days, we are certain that the purity is high, maybe around 50-90% (and probably much closer to 90%, as the paper itself suggests). There is still some contamination but the paper explains why this can happen and how to get rid of it (recrystallization).

The problem is that

1. We got remarkably little of "the goodies" in crude form (less than 1 g or ml), and that seems to be very little, seeing that we began the extraction process with a reaction mixture of 100 ml (which we then diluted with another 100 ml of dichloromethane [DCM] as solvent). The paper didn't say how much to add, so we thought to add as much as we have in the reaction mixture is fair?

We would have after concentration expected at least an output of a few g, maybe even more of "the goodies" ... unfortunately, the paper doesn't say how much we should expect. But we fear that we lost most of "the goodies" somehow during the extraction, washing, drying, and/or during concentration process.

2. After concentration, we didn't get "the goodies" in a yellow crystallized crude form (as the paper suggests; the color yellow would come from the contaminant), but in form of a thick viscuous dark-brown liquid of the consistency of resina (but not gluey).

We suppose it is dark-brown and not yellow, because we somehow lost most of "the goodies," thus there is a disproportional amount of contaminant left in relation to the amount of the product we obtained. If we put a calculated amount of the thick viscuous dark-brown liquid on a spoon, add 10 ml of water, and cook it, "the goodies" get released from the dark-brown liquid, while the dark-brown contaminant simply swims on top and can be easily filtered out.

So we are certain we got what we want (and in the strength/purity we want), we just fear we lost most of it during washing, extraction, drying and/or concentration.

To start with the last thing, the concentration, we don't have access to a rotary evaporator to begin with. We started with "the goodies" in HCl form dissolved in about 60 ml of DCM, and simply evaporated/boiled the DCM away (which happens to have a boiling point of 39.2 °C, while the product has a melting point in excess of 100 °C), so we got rid of all the DCM by boiling it away (with excellent ventilation, far away from other living beings) at around 45° C until it was gone, leaving us with "the goodies" and a contaminant in the form described.

Could this be part of the problem? Should we simply get a rotary evaporator? On the other hand, we don't see how we could lose most of the "goodies" in this process of slow boiling, but it might explain why we weren't left with crystals but rather this dark-brown goo.

Let's quickly look over the other steps, too.

Here is what the article says about extraction, washing, and drying:

The reaction mixture was then diluted with dichloromethane ...

We added 100 ml of DCM to 100 ml of reaction mixture. Is that okay?

... and washed with 4% aqueous sodium hydroxide solution followed by water.

We washed 3 x, each with about 40 ml of 4% aqueous sodium hydroxide solution. We trashed the aqueous layer, and kept the organic layer.

Then we washed 3 x more, each time with about 40 ml of destilled water. We trashed the aqueous phase, and kept the organic phase.

Is this too much washing?

The organic phase was then shaken with 2N HCl. The organic layer was separated and the aqueous layer was extracted with DCM.

Here we might have messed up. What does this mean? *confused*

Here are more details from the paper about what should happen in this process:

The product was purified by shaking organic phase with 2 N HCl which converted all the basic compounds along with desired product in to their hydrochloride salts. The organic phase was separated and washed well with water. The non-polar "goodies"-hydrochloride remained in the dichloromethane layer.

We have 36% HCl (what is allegedly about 12 N). So we created about 120 ml of a 1 : 5 HCl : destilled water mixture (what is about 2 N).

We mixed the organic phase from above with 40 ml of it, shook, vented, shook, vented, etc., until no gas was coming out of the separation funnel anymore, then we trashed the aqueous layer and kept the organic layer (containing the DCM).

We repeated this step 3 x also, always keeping the organic phase (solved in the DCM), trashing the aqueous layer (containing the unwanted polar molecules). The last time, the aqueous layer was totally transparent.

Thereafter we washed once again with destilled water.

Combined organic phase was dried over sodium sulfate and concentrated to give crude HCl salt of "the goodies". Crude product was recrystallised with acetone to give powder of 'the goodies' hydrochloride.

We are pretty confident we did the drying and filtering correct. But what does "combined" mean? What were we supposed to combine? Has this something to do with the sentence/instructions above, of which we are not sure that we understood them correctly? What are we supposed to combine?

Are we supposed to add DCM to the aquaeous layer(s), too (which we trashed), shake/vent it, separate it, and then keep the DCM layer, combining it with the previous DCM layer (which we kept)?

Is this where we might have lost most of product? How do you understand these sentences/instructions?

Since we didn't have any salt, we couldn't recrystallize anything either. Not certain how we would do this, though. Simply add some acetone to the crude product (assuming we have hydrochloride crystals in the first place) and it would recrystallize by itself?

If we didn't do something wrong, maybe all we need is really a rotary evaporator? There is probably a good reason why these things exist? :D

Thank you for all opinions, advise, and help!

[Edited on 30-6-2019 by Li Jun]
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Tsjerk
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[*] posted on 30-6-2019 at 09:06


I'm perfectly fine with helping you, whatever the "goodies" are, but I won't without knowing what they are. I don't like speculations and I can't help you without speculating when I don't know what you are talking about.

A rotary evaporator is a very nice unit to have, but when you are skilled enough you can work around it (in most cases).
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Li Jun
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[*] posted on 30-6-2019 at 09:37


Quote:

I'm perfectly fine with helping you, whatever the "goodies" are, but I won't without knowing what they are. I don't like speculations and I can't help you without speculating when I don't know what you are talking about.

Sorry, I did not add it, because I am not familiar with the forum's rules/guidelines. The product might be illegal to produce without special permission in many countries (but not in mine), which are usually only given to selected pharmaceutical industries (big players), and I didn't want to bring the owners/operators/the board in legal trouble by asking for instructions how to yield a better output of something that might be illegal wherever the board is located (as I have also no idea where this actually is).


[Edited on 30-6-2019 by Li Jun]
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[*] posted on 30-6-2019 at 09:49


You probably have more luck with the admins/moderaters when you state what you are talking about. They decide whether or not to allow your topic. But as far as I know this is the common consensus:

Quote: Originally posted by Polverone  
It's probably spitting into the wind but I would like to remind everyone that the legal restrictions (or lack thereof) on possessing/manufacturing a substance has never been a reason for me to shut down discussions here. Hence the large, flourishing Energetic Materials section. I would actually enjoy more discussion of novel psychoactive substances here, or novel routes to popular materials. Much how I enjoy new substances or synthetic routes to energetic materials when they're discussed in the EM section. The USA has some of the most overbearing synthetic drug laws but some of the most permissive free speech laws in the world, so there is no risk to the forum or myself from discussing any chemistry here no matter how great the legal penalties might be if you get caught trying to implement said chemistry in your own home.

I don't like low-effort threads started by people who are apparently just looking for a quick way to get high or get rich. Nor do I like low-effort threads started by people who just want to make a big, impressive explosion without too much work. But I am never going to lock a thread just because it might be a felony to do the chemistry where I live, or where some other members live. Everything is fine to write about and some members may be more risk-tolerant or lucky enough to live in less legally uptight jurisdictions. The legal considerations, like the personal safety risks, are the responsibility and choice of the individual contemplating doing some chemistry.

So please, feel free to discuss synthetic routes to this ketamine metabolite or any other interesting molecule that crosses your mind.


Edit: Polverone is the owner of the forum.

[Edited on 30-6-2019 by Tsjerk]
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Li Jun
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[*] posted on 30-6-2019 at 10:00


OK, thanks, I didn't know this. Just didn't want to bring anybody into trouble. We are talking about Fentanyl HCl. Thanks, America, for shutting down my Chinese supplier.
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[*] posted on 30-6-2019 at 10:30


Even knowing you are making fentanyl HCl I still don't get what you are saying... I can't smell what you mean.

Also I don't think this is what Polverone meant when he said "new" or "novel". Sounds like very detailed cookery to me.

[Edited on 30-6-2019 by Tsjerk]
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[*] posted on 30-6-2019 at 17:58


No, discussing drug synthesis here wont give us trouble, this isnt china…



Useful sites:
Balance Chemical Equation: http://www.webqc.org/balance.php
Molecular mass and elemental composition calculator: https://www.webqc.org/mmcalc.php
Solubility table: https://en.wikipedia.org/wiki/Solubility_table
Azeotrope table: https://en.wikipedia.org/wiki/Azeotrope_tablesIt's not crime if noone finds out - Nyaruko
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[*] posted on 30-6-2019 at 22:53


On the one hand, I think fentanyl is a very nasty thing that can ruin people's lives.

On the other hand, impure fentanyl (or fentanyl of unknown purity) is probably even worse.

I won't provide specific advice, but I would suggest that you do some reading on acid/base workups. A good starting point is here: https://en.wikipedia.org/wiki/Acid-base_extraction

You should also look up the pKa of the protonated form of the product, and also its partition coefficient. I'm sure the data exist somewhere in a pharmaceutical patent. Until the workup is optimized, don't throw away any of the layers. Save them so that you can figure out where the product is going.

Fentanyl kills people, and I would strongly suggest you reconsider what you're doing. But if you must do it, make sure you get it right.




As below, so above.
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[*] posted on 1-7-2019 at 05:07


Fentanyl seems to have a pka of 7.3, (acidic), i suppose that you extracted it in your water layer with NaOH, the one you threw away.
Anyway the problem is that you followed a paper without even trying to understand the chemistry behind, we could discuss this topic further but in my opinion is just spoonfeeding, you are not interested in the chemistry or the learning possibilities given by this synthesis, you are after the goodies, it's quite clear. The only critique you gave yourself is "we are just following instructions, we have no idea of anything we are doing".
You want to make drugs? Great, but at least have the time to learn the meaning of each action in the "instructions" you are following, by doing this you can solve most problems (like not throwing away the wrong phase) and maybe make a better product, drugs are bad enough, there's no need to make them worse by not cleaning and purify them enough.





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[*] posted on 1-7-2019 at 12:14


You don't understand basic organic workups and, at the same time, you're working with a compound that has a lethal dose of 2 milligrams? Drug chemistry is interesting and fun, but you really should stop before you inadvertently poison yourself and whoever has the misfortune of discovering your lifeless corpse.
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[*] posted on 1-7-2019 at 13:39


Closed.
Not for fentanyl, but for spoonfeeding request.
Nothing good will come from this one.




If you are interested, take a look at the latest offering from sum_lab:
A primer on metals and non-metals with at least one novel experiment.
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