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Topic: Solvent Systems  (Read 3372 times)

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Offline beakers13

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Solvent Systems
« on: March 02, 2016, 12:38:54 AM »
I know generally when coming up with a solvent system one usually uses DCM/methanol or hexanes/ethyl acetate. Why are these always paired together, why can't you use DCM/ethyl acetate? I know although DCM and hexanes are nonpolar, DCM is more polar than hexanes and methanol is more polar than ethyl acetate. This would mean the DCM/ethyl acetate may seem like a better system if a small amount of methanol is too polar, why is this never used?

Offline Dan

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Re: Solvent Systems
« Reply #1 on: March 02, 2016, 03:14:30 AM »
People get set in their ways, that's all. I don't understand it either. I was working with a particularly tricky compound class about 18 months ago, which my colleagues told me were impossible to purify by flash chromatography. This is true if the only thing you attempt is hexanes/EtOAc, but chromatography was straightforward with a hexanes/toluene/acetone/AcOH mixture - that is a complex example, but my point is that if you are adventurous with chromatography solvents, you can purify almost anything.

You can use DCM/EtOAc, I have on several occasions.

I always recommend experimenting with solvents for tough separations, because the Rf differences can change significantly with different solvents (and sometimes elution order will even change). For example, I often find hexanes/acetone gives better separation than hexanes/EtOAc, and hexanes/acetone is normally my first port of call with an unfamiliar reaction. I usually use combinations of:

Weak solvents: alkanes, toluene, DCM
Strong solvents: diethyl ether, EtOAc, acetone
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Offline zarhym

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Re: Solvent Systems
« Reply #2 on: March 04, 2016, 03:38:47 AM »
You have to consider polarity and solubility at the same time. These two combinations are kind of balanced on both sides. They also cover a very broad range of polarity. Perhaps, this is the reason these two solvent system are commonly used.

There is no rule in chemistry saying you have to use these two solvent systems in flash column. If you find some system good for your purification, go ahead and use it.

Offline BRSM

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Re: Solvent Systems
« Reply #3 on: March 06, 2016, 04:04:03 PM »
I think the answer is twofold: 1. These systems are a good one-size-fits-all to try first---if it ain't broke, don't fix it; and 2. People are very dogmatic, especially when they lack experience. They see these systems in the lab/literature and use them, the work, and they end up in the literature again.

To answer your specific question, people do. EtOAc/DCM is actually a good system if you want something with more dissolving power than an EtOAc/hydrocarbon system but an eluent that's less polar than a DCM/MeOH system. If at all possible I prefer EtOAc/MeOH to MeOH/DCM as it's way less toxic and doesn't go through gloves so fast.

Miscibility can also be an important factor: methanol/hexanes don't mix well, and acetonitrile/hexanes are totally immiscible, so don't waste your time on those. I saw a first year grad student run a column in methanol hexanes once -- she literally ended up with biphasic fractions in her rack of tubes. Very funny.

There are so many good alternatives if the off-the-shelf systems don't work well. Subbing toluene for hexane in EtOAc/hexanes is a great, slightly more polar alternative with much better dissolving power for (poly)aromatic compounds. Acetonitrile/toluene or acetone/toluene are also great for more polar compounds. Toluene/hexanes is nice for apolar polyaromatics---I had great success separating regioisomers of a bromonaphthalene in this.

Sometimes you get desperate and try odd mixtures. A labmate of mine just ran a column in hexanes/THF as it was the only thing after 6 hours of TLC-ing that separated her diastereomers. I ran a column in MTBE/i-PrOH/Hexanes a couple of years ago for lack of anything reasonable that worked.

My PhD supervisor said that during his graduate studies in the 70s, acetone/CHCl3 was a very popular mixture, but it's fallen out of favor as CHCl3 is kinda toxic and those solvents will react with each other in the presence of trace base (the Bargellini reaction).

There are a few wacky options too: I have columned N-alkylpyridinium salts on silica in aq NH4OH/MeOH/AcOEt, and the famous 4:1:1 n-butanol/acetic acid/water is a classic for purifying unprotected amino acids on silica, although god knows that's it's a pain to rotavap down. I'd also add that 4:1:1 is also good for biotinylated molecules, which are far more polar than they have any right to be.

So I guess what I'm saying is: as you gain experience, and work with tougher mixtures, you'll end up branching out. But EtOAc/hexanes usually a good way to start. And as I'm a process chemist, I should also point out that recrystallizations and distillations are good options too!

Offline mikeB

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Re: Solvent Systems
« Reply #4 on: May 17, 2022, 12:08:18 PM »
I know this an old thread, but one thing I don't like about hexane/EtAcO (or any other polar solvent) mixtures is that many products have poor solubility in it. On several occasions the columns ran "normally" (with my product having a rf of 0.5) but most of my product turn out to be stuck in the celite layer. That's why I started replacing hexanes with toluene or DCM.  Rf and solubility don't necessarily go together.

Mike

Offline rolnor

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Re: Solvent Systems
« Reply #5 on: May 17, 2022, 04:56:32 PM »
You learn a system, how different compounds behave in it and thats why you get dogmatic. EtOAc/Toluene is a much better solvent and is similar to EtOAc/Hexane.

Offline Babcock_Hall

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Re: Solvent Systems
« Reply #6 on: May 18, 2022, 11:04:59 AM »
I have much less experience than some other people here.  However, I can attest to the general need to be empirical and a little creative in trying different solvent systems.

Offline rolnor

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Re: Solvent Systems
« Reply #7 on: May 18, 2022, 04:20:30 PM »
Agree, I was working with separation of a diastereomer derivative and we tried many systems, at last with EtOAc/DCE/Toluene we got baseline separation on silica. This way we could demonstrate a 3-fold better biological activity of one isomer over the other.

Offline kriggy

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Re: Solvent Systems
« Reply #8 on: May 19, 2022, 06:58:21 AM »
You learn a system, how different compounds behave in it and thats why you get dogmatic. EtOAc/Toluene is a much better solvent and is similar to EtOAc/Hexane.

TBH toluene is annoying because its UV active.

Anyway, EtOAc/DCM is solid mix but I think most chemists hace the "if it works dont fix it" attitude.

Offline rolnor

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Re: Solvent Systems
« Reply #9 on: May 20, 2022, 06:01:57 AM »
You can use a hair-dryer or heating-gun to remove toluene, no problem.

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