Chemical Forums
Chemistry Forums for Students => Organic Chemistry Forum => Topic started by: uglepik on July 20, 2011, 04:39:21 AM
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I've recently run some flash columns using chloroform:methanol:water:acetic acid mixtures as eluant. Usually with ratios in this range:
CHCl3: 60-90%
MeOH: 10-30%
H2O: 1-4%
AcOH: 1-3%
A typical eluant would like this: CHCl3:MeOH:H2O:AcOH (80:20:2:1)
Now I have, based on some odd elemental analysis with consistently low ratios for each element, begun to wonder whether such mixtures will dissolve silica and thereby transfer it to your (supposedly) purified product.
Does anyone have any knowledge or experience regarding this? If it happens? To what extent it happens? How to prevent it? Or how to get rid of the silica once it's there?
Most of my compounds are not soluble in neat organic solvents, but need added acid (formic acid, TFA).
Thanks in advance!
Andreas
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Silica (SiO2) is very diffucult to dissolve and requiers either hydrofluoric acid or concetrated hot alkali like NaOH and should not happen with the used eluent.
On the other hand TFA might be able to dissolve silica, but I'm not familiar enough with it to say for certain.
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Greater than 15 % MeOH solutions can dissolve silica, I've seen it happen, you don't get a lot, but it is visible when you evaporate the solvent.
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I've recently run some flash columns using chloroform:methanol:water:acetic acid mixtures as eluant. Usually with ratios in this range:
CHCl3: 60-90%
MeOH: 10-30%
H2O: 1-4%
AcOH: 1-3%
A typical eluant would like this: CHCl3:MeOH:H2O:AcOH (80:20:2:1)
Now I have, based on some odd elemental analysis with consistently low ratios for each element, begun to wonder whether such mixtures will dissolve silica and thereby transfer it to your (supposedly) purified product.
Does anyone have any knowledge or experience regarding this? If it happens? To what extent it happens? How to prevent it? Or how to get rid of the silica once it's there?
Most of my compounds are not soluble in neat organic solvents, but need added acid (formic acid, TFA).
Thanks in advance!
Andreas
Run a sulphate ash test on your products, this will indicate the inorganic content of the material
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I have also heard that methanol in high enough concentrations will dissolve silica. If the product can be redissolved in an organic solvent that does not contain methanol, the silica should fall back out.
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Yes, high percentages of methanol in chloroform in dichloromethane can dissolve silica gel. Using a straight chloroform/methanol mixture, I find that 20% methanol is usually okay, and I have pushed it to 25%. but I wouldn't go any higher than that and expect not to find silica gel in the product. As Babcock_Hall says, redissolving the product in acetonitrile, ethyl acetate, or even DMF if you have the vacuum pump to rotovap it back off, will allow you to filter out the silica gel if you absolutely have to go that high.
I don't know what the addition of water and acetic acid would do, but I would expect that it would make it easier to dissolve the silica gel.
Chloroform:Ethyl Acetate:Acetic Acid mixtures might allow you to get a more polar solvent system without dissolving silica gel - I've never had a problem with silica gel dissolving in any other solvent I've tried.
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The only thing I can add is that I've seen silica dissolving when using 100% EtOAc as eluent. Re-dissolving stuff in a small amount of DCM and filtering seems a fairly good way around it.
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Okay guys, good answers. I guess I'll have to deal with a bit of silica in some of my products :-\
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Contrary to other posts, it doesn't take that much polarity to dissolve _small_ amounts of silica. Hexane-ether mixes can pick up a little, especially if you are concentrating extremely large amounts of solvent relative to the amount of material coming through (trying to isolate a very faint band).
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Someone seriously needs to do an in depth investigation into the solubility of silica in organic solvents. I've heard everything from "no more than 10% MeOH" to "MeOH doesn't dissolve new silica, only dissolved silica gel made through an older process" to opsomath's comment in this thread. I don't know who or what to trust anymore and its getting frustrating.
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Someone seriously needs to do an in depth investigation into the solubility of silica in organic solvents. I've heard everything from "no more than 10% MeOH" to "MeOH doesn't dissolve new silica, only dissolved silica gel made through an older process" to opsomath's comment in this thread. I don't know who or what to trust anymore and its getting frustrating.
Can it really be that such a study has never been done? It sure would be interesting information... And not too hard to do I suppose.
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This is an old topic for this forum … but considering the answers, and the number of views, I felt I had to respond before too many people start believing some of these answers.
Silica gel does not dissolve in organic solvents alone.
Methanol does not dissolve silica gel.
If you have silica gel in your products recovered after chromatography, it is because the Silica gel of … for example, 43-75 microns … ALSO has a lot of what are called ‘fines’. Fines are particles of silica very much smaller than the stated size formed after sizing. This happens because silica gel particles are not that strong and break up fairly easily. These smaller particles cannot be retained by the frit at the end of the column, and therefore wind up in small amounts in chromatographic eluent. After evaporation of the solvent, the substance of interest is still there, and so are the silica gel fines.
Silica gel does not dissolve in organic solvents alone.
Methanol does not dissolve silica gel.
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if you are going to use an eluent that polar then you may want to consider using a reverse phase column.
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I was using MeOH + water (vol:vol = 1:4) as eluent and found that some of the silica was coming out with the eluent. So, initially I thought it could be the MeOH dissolving silica particles. Thereafter, I prepared a different silica column where I used only water as eluent, I found the same was repeated, some particles came out with the eluent. So, I continued to flush using water as eluent till the clean and transparent water came out of the column. This gave me the understanding that there are finer silica particles which are much smaller than the specified sizes by the manufacturer.
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This is an old topic for this forum … but considering the answers, and the number of views, I felt I had to respond before too many people start believing some of these answers.
Silica gel does not dissolve in organic solvents alone.
Methanol does not dissolve silica gel.
If you have silica gel in your products recovered after chromatography, it is because the Silica gel of … for example, 43-75 microns … ALSO has a lot of what are called ‘fines’. Fines are particles of silica very much smaller than the stated size formed after sizing. This happens because silica gel particles are not that strong and break up fairly easily. These smaller particles cannot be retained by the frit at the end of the column, and therefore wind up in small amounts in chromatographic eluent. After evaporation of the solvent, the substance of interest is still there, and so are the silica gel fines.
Silica gel does not dissolve in organic solvents alone.
Methanol does not dissolve silica gel.
How can you be so sure?
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Rolnor, the post you quoted was from Sept 2015, and I haven't seen that name in a while. I doubt he will respond.
In terms of studying this, it seems to me that dynamic light scattering would be the way to look at this. You take silica gel, suspend it in some solvent or solvent mixture, filter it through a frit that should stop the gel, and put it on DLS. If the silica is truly dissolved there won't be particles, if its just suspended, there will be a DLS profile of particle sizes.
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Thanks, i missed the date. It could be that very small particles breaks loose from the gel when polar protic solvents are used. I really think someone should look in to this, many of my collegues have observed this when working with nucleosides. DLS sounds like a good start.
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Here is a brief "study" supporting the idea that granular silica gel can shed some fines:
http://www.flash-purification.com/does-methanol-really-dissolve-silica-during-flash-column-chromatography/
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Although SiO2 is considered to be water insoluble, it forms colloids and hydrogels with water that deteriorate the separation. Methanol further boosts that hydrogel formation. Besides, there is more than 5% water in the typical eluent because super-dry methanol and/or glacial acetic are unlike to be used. As a conclusion, water must be avoided in normal chromatography.
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According to the link above the problem seems to be not so big but to avoid it spherical silica is better.
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I think that I had this problem of dissolving silica in MeOH, or even more correctly reacting it with my compound.
I used silica gel column chromatography to purify a partial ester of bisphosphonic acid and used gradient elution with DCM/MeOH mixtures. I ended up with rather low yield of my product even though my crude was composed mainly of the desired product. Moreover, according to NMR 1H the “silica complex” of my bisphosphonic acid partial ester had the right integration of hydrogens as “normal” non-silica containing product, but the peaks were all broadened. And this silica containing product was elited with a lot of MeOH