If you don't want to read the details of my life story, skip ahead to the next bold part. That's my real question.
Hi guys, this is my first post in the forum- I'm looking forward to participating in this community, as I very much enjoy Chemistry, and that's why it's my major. I volunteer in a research lab, working on making protein modulators for specific proteins. I'm not allowed to talk very much about it, but there you go- it's organic synthesis.
It's actually been quite a while since I've had an organic chemistry course, and I have a problem:
I'm protecting an alcohol with an ester, and then performing a friedel crafts acylation on the parent molecule. This gives me an ester and a ketone in my target molecule. I only had about 50% yield- leaving me with a large quantity of acid chloride. I need to get rid of it, and for some reason, washing with water doesn't wash it out. My instructor said that some acid chlorides are resistant to water washing. (TLC shows that it remains the acid chloride rather than becoming the carboxylic acid.)
I didn't want to run a column, because I'm doing several reactions in parallel, which would mean running like 7 columns. So I thought maybe I could attack the acid chloride with a water soluble nucleophile that is less reactive than a chloride, but more reactive than the ester-- so that I don't end up actually decomposing my product. I remember that acid chlorides are more reactive than anhydrides, which are more reactive than sulfonic esters, which are in turn more reactive than esters, and ketones and aldehydes, etc... The point of this is that the nucleophile that I attach to the unreacted acid chloride would then lend water solubility to this new acyl compound.
So I thought of selecting an anhydride because it would not destroy my ester, but it would indeed attack the acid chloride. Then I could simply wash off the new acyl compound, leaving my product in the organic layer. The problem I saw with this is that my anhydride might decompose into alcohols, which I have already found not to be water soluble (the rest of the molecule is too greasy, i suppose). So the question at the heart of this is: will an anhydride decompose into two alcohols under neutral conditions? Or does a base need to be present to pluck off the hydrogen from the water molecule that attacks the acyl carbon?
Ultimately, the compounds would probably be in the separatory funnel for a few minutes.
I suppose I could also use a sulfonic ester, but I've never actually used one before. Can anyone recommend a water soluble one? My initial thought was nitro groups because they're so polar, but then I realized the nitrogen would act as a nucleophile as well, and would mess up the product. Then I thought maybe some alcohols would help, for their hydrogen bonding business. Phosphate maybe?