Synthesis of Hydroxylated and Methoxylated Polybrominated Diphenyl Ethers − Natural Products and Potential Polybrominated Diphenyl Ether Metabolites

• Published in: European journal of organic chemistry 2003-07, Vol.2003 (14), p.2566-2576
• Main Authors: Marsh, Göran, Stenutz, Roland, Bergman, Åke
• Format: Article
• Language: English
• Subjects: Aromatic substitution; Halogenation; Natural products; Oxidations; Polybrominated diphenyl ethers
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.200300081

Hydroxylated and methoxylated polybrominated diphenyl ethers (OH‐PBDEs and MeO‐PBDEs) may be natural products or they may be formed as metabolites of polybrominated diphenyl ethers (PBDEs), frequently used as flame retardants. The aim of this work was to synthesize authentic OH‐ and MeO‐PBDE reference standards for analytical and toxicological studies. Brominated phenoxybenzaldehydes were prepared either by coupling of 2,4‐dibromophenol with various fluorobenzaldehydes or by coupling of brominated hydroxybenzaldehydes with 2,2′,4,4′‐tetrabromodiphenyliodonium chloride. OH‐PBDEs were synthesized via the brominated phenoxybenzaldehydes by Baeyer−Villiger oxidation and acid‐catalyzed hydrolysis. These OH‐PBDEs were ortho‐ and para‐brominated (relative to the hydroxy group) with benzyltrimethylammonium tribromide and/or ortho‐brominated with bromine/tert‐butylamine, and were also brominated with bromine in one case. MeO‐PBDEs were obtained by methylation of the prepared OH‐PBDEs. MeO‐PBDEs were also prepared through the coupling of brominated methoxyphenols with 2,2′,4,4′‐tetrabromodiphenyliodonium salts, the corresponding OH‐PBDEs being obtained after demethylation. A majority of the OH‐/MeO‐PBDEs prepared have the hydroxy/methoxy group in the ortho position relative to the diphenyl ether bond. All OH‐/MeO‐PBDEs prepared have 2,4‐dibromo substitution patterns (relative to the diphenyl ether bond) in the non‐hydroxy‐/non‐methoxy‐containing ring. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003)