Bromination of 2-methoxydiphenyl ether to an average of tetrabrominated 2-methoxydiphenyl ethers

Brominated 2-phenoxyanisoles (2-methoxydiphenyl ethers, 2-MeO-BDEs) are a class of halogenated natural products, produced by algae and sponges. Especially two tetrabrominated isomers, i.e. 2′-MeO-BDE 68 (BC-2) and 6-MeO-BDE 47 (BC-3), have also been frequently determined in environmental and food samples. In addition, 2-MeO-BDEs are under discussion as metabolites of polybrominated diphenyl ethers (PBDEs). In this study, we synthesized the backbone 2-methoxydiphenyl ether and brominated it to an average degree of four bromine substituents. The reaction mixture only contained one major product (∼90%) along with three further MeO-BDEs and ∼5% hydroxylated BDEs. In all likelihood, the HO-BDEs were formed in a side reaction by cleavage of the methoxy group. The major MeO-BDE was identified as 6′-methoxy-2,3′,4,4′-tetrabromodiphenyl ether (6′-MeO-BDE-66). The HO-BDEs were separated by KOH/n-hexane partitioning, and the resulting 2-MeO-BDEs were fractionated by means of high-speed counter-current chromatography (HSCCC). Due to the excellent enrichment facilities of HSCCC, some 15 MeO-BDEs, mainly present at traces only, could be detected in 26 fractions, and eight of them could be characterized by nuclear magnetic resonance spectroscopy (NMR). Only two of the compounds – 2′-MeO-BDE 68 and 6-MeO-BDE 123 – had been characterized as natural products while the prominent halogenated natural product 6-MeO-BDE 47 was not detected at all in the reaction product. The “non-natural” 2-MeO-BDEs may be useful internal standards in trace analysis.

► Brominated 2-methoxydiphenyl ethers (2-MeO-BDEs) are environmental contaminants of both natural and anthropogenic origins.
► We synthesized 2-methoxydiphenyl ether and brominated it to an average degree of four substituents.
► The major compound, 6′-methoxy-2,3′,4,4′-tetrabromodiphenyl ether (6′-MeO-BDE-66) accounted for ∼90% of the crude product.
► High-speed counter-current chromatography was used to fractionate the crude product.
► Eight – including five novel – 2-MeO-BDEs could be characterized by NMR.