Hi! I am trying to solve a process for isolating the product of a reaction from the reagents. Basically there's a salicylic acid derivative created, in the presence of nitromethane, ammonium acetate, in an ethanol solution.
Removing the salicylic acid at the end is easy: add water, cool, the salicylic acid drops out of suspension and crystallizes, then either filter or decant + evaporate then wash a couple times in hot water and recrystallize / evaporate to purify. HOWEVER, I believe the ammonium acetate will also drop out of suspension and crystallize, and I need to remove that prior? Or I could try crystallizing the salicylic acid, probably get a bunch of ammonium acetate crystals in the process, decant those from the nitromethane and ethanol, wash, and come up with a final step to separate from the ammonium acetate?

Edited July 23Jul 23 by lexxatron

Ammonium acetate will not crystilize. Check it's soloubilty.

So where I've gotten thus far is: ammonium acetate's 1000x more soluble in water than salicylic acid, so any crystallizing would be the salicylic acid derivative and then mechanical separation. Adding water to the mixture will most likely cause the nitromethane to mostly separate as well, due to its poor miscibility with water - the ethanol will fully mix with the water and the nitro will mostly separate out, so a separatory vessel takes care of that (mostly).

One question is where the salicylic acid prefers ethanol or nitromethane - I mean, either way I can separate it out. But given salicylic acid transforms >70*C, using distillation is out of the question, and vacuum distillation's a step more fancy than I think I can pull off.

Nitro methane is a reactant and will be consumed. Ethanol is the solvent.

The product is 5-(2 Nitro-Vinyl) salicylic acid. Not Salicylic acid itself.

Edited July 25Jul 25 by chenbeier

18 minutes ago, chenbeier said:

Nitro methane is a reactant and will be consumed. Ethanol is the solvent.

The product is 5-(2 Nitro-Vinyl) salicylic acid. Not Salicylic acid itself.

Yes but they are trying to get rid of the residual salicylic acid, aren't they?

So the nitromethane ends up donating its NO2, and in the presence of ammonium acetate is further reacts to end up with a negatively charged acetate and a free ammonia?

13 minutes ago, exchemist said:

Yes but they are trying to get rid of the residual salicylic acid, aren't they?

Ideally 100% conversion to the salicylic acid derivative, but a little bit of unreacted product is acceptable. It's more the reactants and other end products I want to remove after. I'm checking solubility tables and it looks like just by adding water to the ethanol, the salicylic acid derivative (assuming it has similar properties) should drop out of solution, at which point I can decant and then evaporate.

18 minutes ago, exchemist said:

Yes but they are trying to get rid of the residual salicylic acid, aren't they?

For this we need more information about procedure of the reaction, amount of reactants, mechanism, solubilities each components, yield, etc.

Without all this I would choose more nitromethane as the formyl salicylic acid, to get maximum tranzformed to the product.

Edited July 25Jul 25 by chenbeier

14 minutes ago, chenbeier said:

For this we need more information about procedure of the reaction, amount of reactants, Mechanism, solubilities each components, etc.

Yeah unfortunately the above diagram is all I have here. I've contacted the researchers inquiring as to methodology specifics so I can tinker until I manage to recreate it.

Am I wrong in thinking that the format of the published reaction is a bit wrong here? ammonium acetate and nitromethane are shown above the line, where reagents, catalysts etc go. Except it looks like the nitromethane is consumed in the reaction which makes it a reactant and belonging on the left side of the equation and not above the line. Same with the ammonium acetate I think?

The mechanism is a Henryreaction. Its a Nitroaldolreaction

https://en.m.wikipedia.org/wiki/Henry_reaction

42 minutes ago, chenbeier said:

The mechanism is a Henryreaction. Its a Nitroaldolreaction

https://en.m.wikipedia.org/wiki/Henry_reaction

Hmm. Then I think that the ammonium acetate is there because when it breaks into ammonia and acetic acid in solution, the ammonia can function as a weak base to catalyze the nitroaldol reaction required to remove the NO2 group from the nitromethane.

You didn't got the mechanism The whole Nitromethan will be built in

R-CHO + CH3NO2 => R-CH=CHNO2 + H2O

Read about Aldol and the exchange to CH acide CH3NO2 instead of CH3CHO

Ammonium acetate works as a buffer to keep pH stable.

The ammonium acetate is water soluble and easily separated from the 5-formylsalicylic acid reactant and the SANA product using an organic/aqueous extraction, done at acidic pH to be sure that the salicylic acid derivatives are mostly protonated, in which case they are much more soluble in the organic phase (especially the product, which has a significantly lower % polar surface area). It seems to me that the difficult part is separating the SANA product from any unreacted 5-formylsalicylic acid, as these are likely to have a similar pKa. The electron-withdrawing effect of the nitro group on the conjugated system would be expected to lower the pKa of the former slightly relative to the latter, but this effect may well be small given how far away it is from the carboxyl and the fact that the two are not in direct resonance--quite possibly too small to find a pH where the product is >90% ionized yet <1% of the reactant is.

21 hours ago, SFBayFMT5 said:

The ammonium acetate is water soluble and easily separated from the 5-formylsalicylic acid reactant and the SANA product using an organic/aqueous extraction, done at acidic pH to be sure that the salicylic acid derivatives are mostly protonated, in which case they are much more soluble in the organic phase (especially the product, which has a significantly lower % polar surface area). It seems to me that the difficult part is separating the SANA product from any unreacted 5-formylsalicylic acid, as these are likely to have a similar pKa. The electron-withdrawing effect of the nitro group on the conjugated system would be expected to lower the pKa of the former slightly relative to the latter, but this effect may well be small given how far away it is from the carboxyl and the fact that the two are not in direct resonance--quite possibly too small to find a pH where the product is >90% ionized yet <1% of the reactant is.

For this reason it would be nice to know the yield of this reaction. Also I would suggested to add high amount of Nitomethane, so that the amount of the 5-Formyl salicylic acid is low a possible after reaction

17 hours ago, chenbeier said:

For this reason it would be nice to know the yield of this reaction. Also I would suggested to add high amount of Nitomethane, so that the amount of the 5-Formyl salicylic acid is low a possible after reaction

Per the researchers, their yield is 93% of theoretical.