Identification and recovery of an asymmetric calix[4]arene tetranitrile derivative using liquid chromatography and mass spectrometry

A simple analytical liquid chromatography mass spectrometry (LC-MS) method and associated instrumentation has been adapted for use by the organic chemist to yield milligram quantities of target compound from a reaction mixture. Calix[4]arene 3 was identified as representing 51% of total peak area of a reaction mixture containing no less than 10 components, using LC-MS. This peak corresponded to a mass of 878.8, equivalent to a complex of 3 and an ammonium cation. Molecular models further rationalize this observation by showing that the asymmetric binding cavity of 3 is suitable for binding tetrahedral guests such as the ammonium ion. By scaling up the LC method, using analytical instrumentation, 55 mg of 98% pure 3 was isolated with a recovery yield of 90% in 1 h. The current method represents a powerful and easily adapted tool for monitoring a challenging synthesis that combines identification, efficient separation and partial characterization for reaction mixture components using readily available instrumentation and methods.