Replacement of aromatic fluorine by a methoxy group during reaction with methyl iodide inN,N-dimethylformamide solvent

Abstract

The DNA base uracil was derivatized with pentafluorobenzoyl chloride, followed by methylation with methyl iodide in the presence of N,N-dimethylformamide (DMF). In addition to a 3-pentafluorobenzoyl-1-methyl derivative of uracil, GC/MS analysis of the reaction mixture revealed the formation of an unusual product, whose molecular weight was 12 U higher than that of the prior derivative. This unexpected product has been identified as the 3-(para-methoxytetrafluorobenzoyl)-1-methyl derivative of uracil. Isotopic labeling and related experiments have revealed that the DMF solvent contributes the oxygen atom of the methoxy group that replaces the para fluorine atom. This work allowed a single derivative to be obtained for the methylation reaction by changing the solvent to acetonitrile.

Derivatization in trace organic analysis: selection of an inert solvent

“…This is in spite of many examples in the general literature of solvents participating in chemical reactions, including some analytical reactions (e.g. ref 1).…”