I'm new here and this is my first post, also english is not my main language so sorry in advance if I make any mistakes.
So, the problem that I have is that I need to prepare a mixed anhydride from a carboxylic acid and methanesulfonyl chloride and triethylamine, as an activation method for the preparation of a certain amide. I've found in the available literature that, when carrying out this reaction, two other subproducts may be obtained: the symmetric anhydride and the acyl chloride.
Neither the starting carboxylic acid, nor the products can be analysed by gas chromatography since they rather decompose or are not volatile enough. So, we are trying to monitor the reaction by HPLC analysis, using a reverse phase column and a water:solvent mixture as the eluent.
The problem is that the mixed anhydride, the symmetric anhydride and the acyl chloride are readily hydrolyzed by the aqueous mobile phase, so some derivatization method must be found in order to differentiate the aforementioned compounds. The thing is that, for the symmetric anhydride, if you use a nucleophile as a derivatizing agent, such as an amine or alcohol, for each derivatized molecule you also get a caboxylic acid molecule as a subproduct. As a result, you never know if the acid that you are seeing comes from the derivatization or from an incomplete reaction, thus making this monitoring method useless for the needed purpose. The other obvious problem with nucleophilic derivitizing agents is that the mixed anhydride, the symmetric anhydride and the acyl chloride give all the same product.
Any ideas about how to differentiate this compounds in an HPLC analysis?
Thanks in advance!