[Babcock_Hall]

My student accidentally prepared some ethyl acetate with 4% acetic acid, not 1 %.  He was supposed to use 4% methanol and 1 % acetic acid (it's a long story).  Is 4% too much in terms of possibly dissolving the silica?

[blackcat]

I personally think no. It won't dissolve for 4% HOAc with 96% EA.

Indeed, theoretically methanol or ethanol can dissolve silica column. I once used ethanol to push our my stuff on column. Nothing dissolved.

By the way, usually the addition of a little HOAc additive is for basic alumina column when your stuff is acidic.

[hypervalent_iodine]

Indeed, theoretically methanol or ethanol can dissolve silica column.

I believe this is a myth, albeit a very pervasive one. Silica isn't dissolved by methanol, but it can cause for it to shed fine particles that are able to move through the column. (https://selekt.biotage.com/blog/does-methanol-really-dissolve-silica-during-flash-column-chromatography)

[blackcat]

Yes, very true

[wildfyr]

As long as the column is working fine, the acetic acid won't hurt anything. Think about it, silica gel is just tiny pieces of very porous glass. Glassware does fine containing 100% acetic acid!

[blackcat]

Just try to avoid acetic acid if possible. Use some other polar solvents like DCM/MeOH or EtOH instead.

Acetic acid has a strong smell. With high boiling point (118 oC), it remains with your product, very hard to remove and you can smell the poor acid from your product.

[hypervalent_iodine]

Just try to avoid acetic acid if possible. Use some other polar solvents like DCM/MeOH or EtOH instead.

Acetic acid has a strong smell. With high boiling point (118 oC), it remains with your product, very hard to remove and you can smell the poor acid from your product.

Sometimes MeOH / DCM doesn't quite cut it. It's not that hard with enough vacuum or by the addition of toluene, and can be quite useful when you are separating difficult acids.

[Babcock_Hall]

We thought that we had carboxylic acid present.  In the past we have used 1% acetic acid in the eluting solvent, presumably to ensure that the product is in the protonated form.

[blackcat]

We thought that we had carboxylic acid present.  In the past we have used 1% acetic acid in the eluting solvent, presumably to ensure that the product is in the protonated form.

Then it seems you are running an alumina column, not silica gel column.

1% acetic acid is best described as "additive". It is not something to tune the polarity of the eluting solvent.

[wildfyr]

Kamiyu, with highly polar eluents, I think you'd be surprised what can increase polarity. I see things sometimes in carbohydrate or natural product syntheses where the eluent is things like 90% DCM 8% MeCN 2% Acetic acid.

[Babcock_Hall]

We were indeed running a silica column, but it may have been chloroform/methanol/acetic acid, possibly patterned after Janecka et al., J. Med. Chem. 1994,37, 2238-2241.