Metylering av alkylmetylfosfonsyror för GC-MS-analys med trimetylsilyldiazometan

A method for the methylation of alkyl methylphosphonic acids for GC-MS analysis using the reagent trimethylsilyl diazomethane (TMSD) has been optimized by experimental design. The aim was to develop a method that can replace the traditional methylation based on diazomethane which is toxic, explosive and must be generated shortly before use. Five different alkyl methylphosphonic acids (AMPA) were used in the evaluation of TMSD; methylphosphonic acid (MPA), ethyl methylphosphonic acid (EMPA), isopropyl methylphosphonic acid (IMPA), pinacolyl methylphosphonic acid (PMPA) and cyclohexyl methylphosphonic acid (ChMPA). The parameters evaluated were added amount of methanol, concentration of phosphonic acid, derivatization temperature and time, and choice of solvent. The optimization resulted in a method that gives yields close to 100%. The method is optimal at room temperature, is relatively fast (< 90 minutes), has negligible carry-over in the GC-MS analysis and is not sensitive to traces of water. Methylation with TMSD is a very useful alternative to diazomethane for derivatization of phosphonic acids.