[cheesewithwhine]

My experiment involves hydrolysis of glycine methylester with KOH in methanol. Normally water workup is needed, but glycine ion is soluble in water so it's difficult to retrieve. What can be done to work up the reaction in a way that makes isolating glycine easy?

Thanks!

[Doc Oc]

Using KOH in methanol will not hydrolyze the ester to the acid, you're creating conditions to make the methyl ester again.  You need to use a different solvent.

Aqueous NaOH or KOH solutions will work in the hydrolysis.  Tracking the reaction can be tricky and depends on what tools are available to you.  If you have LC/MS, that's probably the easiest.  After the reaction is done, acidify the aqueous phase to pH 1 and extract several times (5-10 times or more) with ethyl acetate to get your amino acid.

[fledarmus]

KOH in methanol will hydrolyze the glycine. -OH is a better nucleophile than -OEt, and once it is attached, it is deprotonated by the base and no longer undergoes substitution. I don't believe you can make esters with hydroxide bases in any solvent system.

Also, although the extraction would work with most simple carboxylic acids, I don't believe you would be able to extract your glycine from an acid solution using ethyl acetate. Glycine is an amino acid, and at pH 1 that amine would be fully protonated.

You could try adding HCl in either methanol or dioxane to your solution, calculated to just neutralize the KOH that you started with. The solubility of KCl in methanol is much less than the solubility of KOH in methanol, and most of it should precipitate. The when you strip down the methanol, you would be left with glycine contaminated with a small amount of KCl.

Is there a particular reason for carrying out this transformation? It seems like a lot of work to prepare something that is cheap and readily available.