Effects of fluoro substitution on 4-bromodiphenyl ether (PBDE 3)

Abstract

It is our hypothesis that fluoro substitution provides a powerful tool to modulate the desired characteristics and to increase the specificity of studies of structure–activity relationships. 4-Bromodiphenyl ether (PBDE 3) and its five corresponding monofluorinated analogues (F-PBDEs 3) have been synthesized and fully characterized (using 1H, 13C and 19F NMR spectroscopy, and mass spectrometry). The accurate structure from X-ray crystal analysis was compared with iterative calculations using semi-empirical self-consistent field molecular-orbital (SCF-MO) models. The compounds studied were 4-bromodiphenyl ether (PBDE 3), the 13C6-isotopically labeled PBDE 3 (13C6-PBDE 3) and 2-fluoro-4-bromodiphenyl ether (3-2F), 2′-fluoro-4-bromodiphenyl ether (3-2′F), 3-fluoro-4-bromodiphenyl ether (3-3F), 3′-fluoro-4-bromodiphenyl ether (3-3′F), and 4′-fluoro-4-bromodiphenyl ether (3-4′F). Solid-state intermolecular interactions for PBDE 3 and the F-PBDEs 3 isomers are dominated by weak C—H(F,Br)...π and C—H...F interactions. The C—F bond lengths varied between 1.347 (2) and 1.362 (2) Å, and the C4—Br bond length between 1.880 (3) and 1.904 (2) Å. These bond lengths are correlated with electron-density differences, as determined by 13C shifts, but not with the strength of the C—F couplings. The interior ring angles of ipso-fluoro substitution increased (121.9–124.0°) as a result of hyperconjugation, a phenomenon also predicted by the calculation models. An attraction between the vicinal fluoro and halo substituents (observed in fluoro substituted chlorobiphenyls) was not observed for the bromo substituted F-PBDEs. The influence of a fluoro substituent on the conformation was only observable in PBDEs with di-ortho substitution. Calculated and observed torsion angles showed a positive correlation with increasing van der Waals radii and/or the degree of substitution for mono- to tetra-fluoro, chloro, bromo and methyl substitutions in the ortho positions of diphenyl ether. These findings utilizing F-tagged analogues presented here may prove fundamental to the interpretation of the biological effects and toxicities of these persistent environmental pollutants.