Electron-capture detection: difluorobenzyl and related electrophores

Difluorobenzyl derivatives (several isomers were tested) of 4-hydroxyacetophenone were synthesized and found to have similar properties (retention and response) by both reversed-phase HPLC and GC-ECD relative to each other, and also relative to that of a corresponding conventional pentafluorobenzyl derivative. The same was true for a representative difluorobenzyl derivative of thymine and 1-naphthoic acid. Overall, the responses by GC-ECD for the same core structure were only about two- to four-fold lower for a difluorobenzyl compared to a corresponding pentafluorobenzyl derivative. This makes a difluorobenzyl derivative attractive as an HPLC-UV retention marker, and sometimes as a substitute for a pentafluorobenzyl derivative (to help overcome an interference) in a method based on detection by electron capture. We also observed, somewhat as an aside, that the GC-ECD response of the benzyl derivative of 4-hydroxyacetophenone was only seven-fold lower than that of the corresponding pentafluorobenzyl derivative, and that this former benzyl derivative gave a 2.10(4) higher response than acetophenone. Thus, replacing the ring hydrogen atoms of a benzyl group with fluorine atoms had a relatively small impact on both the hydrophobicity and electron capture properties of the compounds tested here.