Synthesis and reaction of ortho-fluoronitroaryl nitroxides. Novel versatile synthons and reagents for spin-labelling studies

Abstract

2-Flurophenyl- and 2,5-bis(fluorophenyl)pyrrolidin-1-oxyls (2 and 6) were synthesized from the corresponding nitrones 1,4, and 5 with the Grignard reagent prepared from 1-bromo-4-fluorobenzene. The reaction of 2,2,5,5-tetramethyl-3-formyl-3-pyrrolin-1-oxyl (8) with (4-FC6H4)2Cd gave 2,2,5,5-tetramethyl-3-(α-hydroxy-4-fluorobenzyl)-3-pyrrolin-1-oxyl (9), which was oxidized with MnO2 to 2,2,5,5-tetramethyl-3-(4-fluorobenzoyl)-3-pyrrolin-1-oxyl (10). The aryl nitroxides 2, 6, and 10 were nitrated with concentrated H2SO4/HNO3 to ortho-fluoronitrophenyl compounds 3, 7, and 11. The fluoro nitro derivatives served as versatile synthons in the nucleophilic replacement of fluorine with OH, NH2, α-amino acid ester, or thiol. The hydroxy nitroaryl compounds 16, 26, and 30 were nitrated further to give dinitrophenol derivatives 17, 27, and 31. Keywords: fluorophenyl nitroxides, nitroaryl nitroxides, NMR spectra of nitroxides.