Improved syntheses of non-dioxin-like polychlorinated biphenyls (PCBs) and some of their sulfur-containing metabolites

Abstract

Polychlorinated biphenyls (PCBs) are an important group of environmental pollutants that have been associated with adverse human health effects. Despite recent advances in their synthesis, the availability of PCB congeners in sufficient quantity and purity still represents one obstacle in the investigation of their biological effects. We report herein improved syntheses of PCB congeners (and their metabolites) containing two or more ortho-chlorine substituents. The Suzuki coupling reaction at 110 °C yielded PCB congeners with a 2,2′-substitution pattern in good yields (78–99%), but failed to give PCB congeners with 3 or 4 ortho chlorine substituents. Symmetrically substituted PCB congeners with multiple ortho chlorine substituents were obtained in 20–52% yields using a modified Ullmann coupling reaction. The yield of the coupling increased with increasing degree of chlorination of the starting material. The modified Ullmann coupling reaction employed much milder reaction conditions (copper–bronze/CuCl in N-methylpyrrolidinone, 110 °C) and, therefore, appears to be advantageous compared to the classical Ullmann coupling reaction (copper–bronze, no solvent, 230 °C). PCBs 136 and 155 prepared via the modified Ullmann coupling reaction were nitrated and reduced with Na 2S 2O 4 to the corresponding amino-PCBs. Subsequently, the amino-PCBs were converted into sulfur-containing PCB metabolites or PCB 184 via the corresponding diazonium salt. These modified reaction conditions allow the synthesis of large quantities of pure, non-dioxin-like PCB congeners and their sulfur-containing metabolites for environmental and toxicological studies by overcoming problems associated with classical PCB synthesis strategies.