Influence of fluoro-substitution on the planarity of 4-chlorobiphenyl (PCB 3)

Abstract

Accurate structure determinations by X-ray crystal analysis and computation using semi-empirical self-consistent field molecular orbital calculations are described and compared for five monofluorinated analogues of 4-chlorobiphenyl, i.e. 2-fluoro-4-chlorobiphenyl, 2'-fluoro-4-chlorobiphenyl, 3-fluoro-4-chlorobiphenyl, 3'-fluoro-4-chlorobiphenyl and 4'-fluoro-4-chlorobiphenyl. Intermolecular interactions for all monofluorinated isomers are dominated by phenyl-phenyl stacking and C-H-phenyl interactions. C-F bond lengths varied between 1.341 and 1.374 A, C-Cl between 1.733 and 1.765 A, and both correlate with electron-density differences as determined by (13)C NMR shifts. The interior ring angles at ipso-fluoro substitution increase up to 122.2-124.2 degrees due to hyperconjugation by 2p-pi-orbital overlapping, a phenomenon that was also reflected in the computer calculation. The angles of C-F and C-Cl relative to the aromatic ring for vicinal fluoro- and chloro substituents show an attraction, not a repulsion, between the adjacent F and Cl substituents. This finding is explained on the basis of electron donor and acceptor properties. The dihedral angles of ortho-substituted biphenyls show that monofluoro substitution results in slightly smaller increases compared with chlorine, while additional ortho-fluorination results in little further change in the dihedral angle. In contrast, ortho-chlorination strongly decreases the co-planarity. This is likely to be due to interior ring-angle distortion and the size of the halogen substituent. Fluoro substitution does indeed affect the planarity of the PCB3 analogues, but these effects are minor compared with chloro substitution. Fluorine tagging offers promise for use in in vitro and in vivo studies. Differences in computational versus measured data emphasize the need to use a variety of methods to ascertain the true nature of the physical properties of a compound.

Thermal degradation of polybrominated diphenyl ethers over as-prepared Fe3O4 micro/nano-material and hypothesized mechanism

“…The stability of a PCB congener will increase as the angle increases, so the generation of multiple-ortho-chlorine-substituted congeners is preferred. As shown in Scheme 1c, the C1…C1′ and C (aromatic) -Cl distances for CB-209 have been calculated to be 1.495 and 1.741 Å, respectively, as comparable to that of the reported 1.48 and 1.747 Å (Luthe et al 2007.…”

“…This angle depends on the PCB's substitution pattern, particularly at the ortho-positions. The dihedral angles of PCBs have been determined to be 35-45°for nonortho-chlorine substitution, 47-51°for mono-ortho-chlorine substitution, 58-68°for di-ortho-chlorine substitution, and 86-87°for tetra-ortho-chlorine substitution (Luthe et al 2007). The stability of a PCB congener will increase as the angle increases, so the generation of multiple-ortho-chlorine-substituted congeners is preferred.…”

“…There are important differences in the structures of PCBs compared with PBDEs owing to the lack of an ether linkage. The conformation of a PCB can be described using the dihedral angle between the benzene rings, which seems to be the most important determinant of the structure (Luthe et al 2007). This angle depends on the PCB's substitution pattern, particularly at the ortho-positions.…”

Receptor interactions by polybrominated diphenyl ethers versus polychlorinated biphenyls: A theoretical structure–activity assessment

“…According to our review of the literature, the experimental dihedral angles determined for non-ortho-chloro substituted PCBs are 35-45°, mono-ortho 47-51°, di-58-68° and tetra 86-87° (Luthe et al, 2007). Based on these findings, the descriptor of PCBs as 'coplanar' is in fact a misnomer.…”

The three-dimensional structure of 3,3′,4,4′-tetrachlorobiphenyl, a dioxin-like polychlorinated biphenyl (PCB)

“…This was contained in the Spartan 02 package and carried out on a Quad 2.5 GHz Power Mac G5 with a PCI express graphic card as described previously (Luthe et al, 2007). The use of symmetry constraints enhanced the convergence compared with completely unconstrained runs.…”