Synthesis of Octabrominated Diphenyl Ethers from Aminodiphenyl

Oct 4, 2007 - products of the high-volume industrial BFR mixture. “DecaBDE”, which most exclusively consists of perbrominated diphenyl ether (BDE-...
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Environ. Sci. Technol. 2007, 41, 7459-7463

Synthesis of Octabrominated Diphenyl Ethers from Aminodiphenyl Ethers DANIEL TECLECHIEL,* ANNA CHRISTIANSSON, ÅKE BERGMAN, AND GO ¨ RAN MARSH Department of Environmental Chemistry, Stockholm University, SE-10691, Stockholm, Sweden

Polybrominated diphenyl ethers (PBDEs) are additive brominated flame retardants (BFRs), which have become widespread pollutants in abiotic and biotic environments including man. Tetra- to hexaBDEs and decaBDE are the most common environmental PBDE contaminants. Congeners of octabromodiphenyl ethers (octaBDEs) originate from used industrial OctaBDE mixtures and from transformation products of the high-volume industrial BFR mixture “DecaBDE”, which most exclusively consists of perbrominated diphenyl ether (BDE-209). The objective of the present work was to develop methods for the synthesis of authentic octaBDE congeners in order to make them available as standards for analytical, toxicological, and stability studies, as well as studies concerning physical-chemical properties. The syntheses of six octaBDEs, 2,2′,3,3′,4,4′,5,5′octabromodiphenyl ether (BDE-194), 2,2′,3,3′,4,4′,5,6′octabromodiphenyl ether (BDE-196), 2,2′,3,3′,4,5,5′,6octabromodiphenyl ether (BDE-198), 2,2′,3,3′,4,5′,6,6′octabromodiphenyl ether (BDE-201), 2,2′,3,3′,5,5′,6,6′octabromodiphenyl ether (BDE-202), and 2,2′,3,4,4′,5,6,6′octabromdipheny ether (BDE-204), are described, of which BDE-204 was prepared via two different pathways. Syntheses of BDE-198, BDE-201, BDE-202, and BDE-204 are based on octabromination of mono- or diaminodiphenyl ethers followed by diazotization and reduction of the amino group(s). BDE-194 and BDE-196 were prepared by bromination of 3,3′,4,4′,5,5′-hexabromodiphenyl ether (BDE169) and 2,3,3′,4,4′,5′,6-heptabromodiphenyl ether (BDE191), respectively, and BDE-169 and BDE-191 were prepared from 4,4′-diaminodiphenyl ether and 3,4′-diamiodiphenyl ether, respectively. The synthesized PBDE congeners are described by 1H NMR, 13C NMR, electron ionization mass spectra, and their melting points.

Introduction Polybrominated diphenyl ethers (PBDEs) are brominated flame retardants (BFRs) with special environmental interest because of their properties as being both persistent and bioaccumulative, i.e., accumulating in wildlife and humans (1-3). Industrial mixtures of PBDEs, i.e., the “PentaBDE”, “OctaBDE”, and “DecaBDE” have been used in large volumes as additives in a variety of articles and polymer products, e.g., in televisions, computers, electric wire coating, textiles, * Corresponding author phone: +46-8-163677; fax: +46-8-163979; e-mail: [email protected]. 10.1021/es071496o CCC: $37.00 Published on Web 10/04/2007

 2007 American Chemical Society

upholstery, and building materials (4-6). Environmental concerns about the “PentaBDE” and “OctaBDE” mixtures led to the ban of these mixtures in the European Union (EU) (7) and to a voluntary halt in production by the sole U.S. producer (8). The present work is focused on chemical synthesis and characterization of individual octabrominated diphenyl ethers (octaBDEs). The octaBDE congeners originate from industrial “OctaBDE” mixtures and from transformation (debromination) of compounds present in industrial DecaBDE, i.e., decabromodiphenyl ether (BDE-209) and about 0.3-3% of nonabromodiphenyl ethers (5, 9). The most important octaBDE congeners present in commercial OctaBDE mixtures are BDE-197, BDE-196, BDE-203, and BDE-201 named in concentration order starting with the most abundant one (10, 11). These compounds and several other octaBDE congeners have been found as transformation products of BDE-209 or industrial DecaBDE in, e.g., anaerobic degradation in sewage sludge (12), fish metabolism (13), and photolysis (14-16). OctaBDEs have been reported to be present in, e.g., sediment (17), house dust (18), tree bark (19), foodstuffs (20), various fish species (21, 22), and human blood (9). BDE-197, BDE-196, and BDE-203 were the identified octaBDE congeners in these works. Limited data are available regarding the toxicity of octaBDEs but BDE-203 has shown neurotoxic effects in mice, i.e., affecting their learning and memory functions (23). The availability of authentic PBDE congeners is a need in environment research for chemical analysis, toxicological studies, and studies on their chemical-physical properties, e.g., photolysis. Synthetic methods for authentic PBDE congeners, with a bromine degree of 1-10 bromine atoms have been described in the scientific literature, except for the octaBDEs. These methods include bromination of diphenyl ether or of a PBDE congener (24-26); bromophenols coupling with symmetrical (24, 27) or unsymmetrical (27) bromodiaryliodonium salts; aromatic nucleophilic substitution reactions (SNAr) by coupling bromophenols with bromoflouronitrobenzenes followed by reduction of the nitro group, diazotization, and Sandmeyer reaction (27); Suzuki coupling by reacting a bromophenol with bromoarylboronic acids (27); and Ullmann diphenyl ether synthesis by coupling bromophenol with bromobenzene (26). Recently, all three nonaBDE congeners were synthesized from monoaminodiphenyl ethers based on perbromination followed by diazotization of the amino group and reduction of the diazonium ion (28). In the present work diaminodiphenyl ethers and monoaminodiphenyl ethers were used for the preparation of six octaBDE congeners. Hence the aim of the present work was to develop synthetic methods for the preparation of authentic octaBDE congeners with the purpose to supply those to analytical, toxicological, and stability studies, as well as to studies concerning physical-chemical properties. Hitherto, no synthetic methods for octaBDE congeners have been described in the literature.

Results and Discussion Here we report the synthesis of six octaBDEs, BDE-194, BDE196, BDE-198, BDE-201, BDE-202, and BDE-204, of which the latter was prepared via two pathways. The hexaBDE, BDE169, and the heptaBDE, BDE-191, which were prepared as precursors to BDE-194 and BDE-196, respectively, are reported as well. The octaBDEs synthesized were characterized by melting points, 1H NMR, 13C NMR, and MS in EI mode. BDE-194, BDE-198, BDE-201, BDE-202, and BDE-204 have been characterized by X-ray crystallography and these VOL. 41, NO. 21, 2007 / ENVIRONMENTAL SCIENCE & TECHNOLOGY

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SCHEME 1

SCHEME 2

data were in accordance with NMR data. The detailed X-ray results are to be published elsewhere. Three octabromodiphenyl ethers, BDE-201, BDE-202, and BDE 204, were synthesized in 7-13% yields from 3,4′diaminodiphenyl ether (2), 4,4′-diaminodiphenyl ether (3), and 3,5-diaminodiphenyl ether (4), respectively, as shown in Scheme 1. Thus, the commercially available diaminodiphenyl ethers 2-4 were perbrominated in an excess of bromine with aluminum bromide as catalyst (29). The perbrominated diaminodiphenyl ethers obtained were diazotized using boron trifluoride diethyl etherate and 3-methylbutyl nitrite (30). The crude diazonium salts were reduced with iron(II)sulfate heptahydrate in DMF (31). This methodology has previously been successfully used for preparation of the two nonabrominated BDE congeners, BDE-207 and BDE-208, synthesized from 3-aminodiphenyl ether (5) and 4-aminodiphenyl ether (1), respectively (28). These two mono-aminodiphenyl ethers were in the present work brominated to obtain octabrominated aminodiphenyl ether products which after diazotization and reduction gave BDE198 (from (1), 9% yield) and BDE-204 (from (5), 30% yield) (Scheme 1). The octaBDE congener obtained from 3-aminodiphenyl ether was previously reported as BDE-197 (28), but this work proves that this octaBDE is BDE-204, as shown by NMR (cf. below) and X-ray crystallography (unpublished). An attempt to synthesize BDE-194 from commercially available 2,2′-diaminodiphenyl ether, which has its two amino groups in the ortho position to the diphenyl ether oxygen failed and no PBDE product was observed. Similarly, the preparation of the nonaBDE, BDE-206, from the mono-amino analogue, 2-aminodiphenyl ether, has previously also been reported to fail (28). In the latter case however, BDE-206 was synthesized by protection (acetylation) of the amino group prior to perbromination. In this work no attempts were done to protect the two amino groups in 2,2′-diaminodiphenyl ether to prepare BDE-194. Instead BDE-194 was prepared from BDE-169 using bromine and iron powder in carbon tetrachloride (CCl4) (Scheme 2). BDE-169 was prepared from 4,4′-aminodiphenyl ether (3) by tetrabromination of the active positions, ortho to the amino groups with bromine in acetic acid, followed by diazotiation (using boron trifluoride diethyl 7460

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etherate and 3-methylbutyl nitrite) and Sandmeyer type of reaction using a mixture of copper(Ι) bromide and copper(ΙΙ) bromide (32) (Scheme 2). BDE-169 has C2 symmetry with all four hydrogens ortho to the diphenyl ether oxygen and two octabrominated products could theoretically be formed (BDE-194 and BDE-205). However, BDE-194 was the only octaBDE formed at the octabromo level in this reaction with a minor nonaBDE as the only byproduct. BDE-196 was prepared from 3,4′ diaminodiphenyl ether (2) via BDE-191 using reaction methodology similar to that for the preparation of BDE-194. The yield of the octaBDEs, BDE-194 and BDE196 were 80% and 94%, respectively. This study shows that single octaBDEs can be prepared in a pure form via polybromination of aminodiphenyl ethers or perbromination of diaminodiphenyl ethers followed by reduction of the amino groups to hydrogens. The limitation seems to be that diphenyl ether precursors with amino groups in ortho positions to the diphenyl ether oxygen cannot be used due to side reactions during the bromination, mainly resulting in ring closures forming polybrominated dibenzofuranes. Protection of the amino group prior to bromination is therefore required as previously described for the perbromination of 2-aminodiphenyl ether, i.e., perbromination of 2-acetamidodiphenyl ether (28). Diaminodiphenyl ethers can also be used for stepwise synthesis of octaBDEs, initially by selective bromination, then by the conversion of amino groups to bromines, and finally by selective bromination of the PBDE congener obtained.

Experimental Section Instruments and Instrument Operational Conditions. Melting points were determined on a Bu ¨ chi 353 apparatus and were not corrected. The 1H NMR and 13C NMR were recorded on a Varian Mercury 400 or a Bruker 400 spectrometer at 400 and 100 MHz, respectively, with TMS as the internal standard in THF-d8 solution at 25 °C unless stated otherwise. Gas chromatography-mass spectrometry (GCMS) was performed on an ion trap GCQ Finnigan Mat instrument. The gas chromatograph was equipped with a fused silica capillary column (DB-5, 15 m × 0.25 mm, 0.1-

SCHEME 3

mm film thickness, J&W Scientific, Folsom, CA). The temperature program was 80 °C for 2 min, raised at 15 °C min-1 to 300 °C which was held for 15 min. The injections were made in the splitless mode using an injection temperature of 260 °C. Helium was used as carrier gas. Mass spectra were recorded in electron ionization mode at an ion source temperature of 150 °C and an electron energy of 70 eV. Mass spectra were scanned from 150 to 1000 m/z. Highperformance liquid chromatography (HPLC) was performed on a Knauer K-501(Berlin, Germany) equipped with an UV detector UV100 from Spectra-Physics (Fremont, CA) and a preparative C18 reversed-phase column (Ace 5 C18, 250 × 21 mm, 5 µm particles) from Advanced Chromatography Technologies (Aberdeen, Scotland). The flow rate was 10 mL min-1, the eluent was 8% methanol and 92% acetonitrile, and the wavelength was set at 310 nm. Chemicals. All organic extracts were dried with anhydrous sodium sulfate before the solvent was evaporated in a rotary evaporator under reduced pressure at temperatures not exceeding 35 °C. Silica gel column chromatography was carried out using MATREX Silica, 60 Å, 35-70 µm, Millipore (Bedford, MA). All solvents, acids, and other chemicals used were of pro analysis quality. The starting materials 3-phenoxyaniline, 4-phenoxyaniline, 2,2′-diaminodiphenyl ether, and 3,4′-diaminodiphenyl ether were purchased from SigmaAldrich Chemie (Steinheim, Germany). 3,5-Diaminodiphenyl ether was from Chemical Block Ltd (Moscow, Russia) and 4,4′-diaminodiphenyl ether was from Lancaster Synthesis Ltd (Newgate, United Kingdom). Synthesis. 2,2′,3,3′,4,5,5′,6-Octabromodiphenyl Ether (BDE198). 4-Phenoxyaniline (1), (0.40 g, 2.07 mmol) in bromine (5 mL, 98 mmol) was added dropwise to a refluxing solution of aluminum tribromide (1.16 g, 4.34 mmol) in bromine (5 mL, 98 mmol) under vigorous stirring. The mixture was refluxed for 1 h. Subsequently, a gentle stream of nitrogen removed the excess bromide and the residue was washed with water (3 × 50 mL), aqueous NaOH (1 M, 3 × 50 mL), and 10% aqueous sodium hydrogen sulfite (50 mL). The solid crude product was dissolved with toluene (100 mL) and washed with water (100 mL). The organic phase was collected and the solvent was evaporated to give a solid brown-yellow crude product of 4-amino-octabromodiphenyl ether (1.79 g). Next, boron trifluoride diethyl etherate (1.25 g, 8.80 mmol, 1.12 mL) was added to the crude product of 4-aminooctabromodiphenyl ether (1.79 g, 2.20 mmol) in THF (10 mL) and the mixture was cooled to -15 °C. 3-Metylbutyl nitrite (1.55 g, 13.2 mmol, 1.8 mL) in THF (5 mL) was added dropwise to the solution during a period of 10 min. The temperature was maintained at -15 °C for 30 min and then allowed to rise to room temperature. The solvent was evaporated and the crude 4-diazonium tetrafluoroborate-

octabromodiphenyl ether (1.79 g, 1.96 mmol) was dissolved in DMF (6 mL). Iron(II)sulfate heptahydrate (1.64 g, 5.88 mmol) in DMF (6 mL) was added dropwise at room temperature and the mixture was stirred for 30 min. Water (100 mL) was added and the mixture was extracted with toluene (3 × 100 mL). The combined organic layers were dried and the solvent was evaporated off. The crude product of BDE-198 was first purified on a silica gel column with n-hexane as the mobile phase, then by preparative HPLC (see above), and finally it was crystallized from acetonitrile/ THF. Yield: 0.14 g, 0.18 mmol, 9%. Mp 221-222 °C. 1H NMR (DMSO-d6): δ ) 7.15 (d, 1H), 7.82 (d, 1H). 13C NMR: δ ) 154.87, 150.23, 131.50, 130.22, 128.40, 128.24, 122.80, 122.41, 117.19, 115.10 ppm. EIMS: m/z [ion] (rel. int. %) 802 [M + 8]+ (6), 642 [M- 2Br + 6]+ (100), 561 [M - 3Br + 4]+ (14), 533 [M - 3BrCO + 4]+ (20), 482 [M - 4Br + 4]+ (32), 454 [M 4BrCO + 4]+ (10), 373 [M -5BrCO + 2]+ (29), 321 [M- 2Br + 3]2+ (42), 267.5 [M - 3BrCO + 2]2+ (15), 241 [M - 4Br + 2]2+ (14), 213 [M - 7BrCO]+ (9). 2,2′,3,3′,4,5′,6,6′-Octabromodiphenyl Ether (BDE-201). To 3,4′-diaminodiphenyl ether (2) (0.41 g, 2.05 mmol) and aluminum tribromide (5.4 g, 20.2 mmol) was added bromine (15 mL, 293 mmol) and the mixture was refluxed for 5 h. The synthesis was then performed as described above for BDE198 with the following crude products obtained. Diazotization of the perbrominated crude product (1.48 g, 1.78 mmol) was carried out with boron trifluoride diethyl etherate (1.0 g, 7.12 mmol, 0.90 mL) in THF (10 mL) and 3-metylbutyl nitrite (1.25 g, 10.7 mmol, 1.44 mL). The diazonium salt was obtained in an amount of 1.48 g (1.44 mmol) and iron(II)sulfate heptahydrate (1.2 g, 4.32 mmol) in DMF (12 mL) was used for the reduction. Yield: 0.12 g, 0.15 mmol, 7%. Mp 198-199 °C. 1H NMR: δ ) 8.07 (s, 1H), 8.10 (s, 1H). 13C NMR: δ ) 152.55, 150.72, 137.45, 133.83, 129.53, 126.72, 121.60, 121.07, 118.98, 113.82 ppm. EIMS: m/z [ion] (rel. int. %) 802 [M + 8]+ (10), 642 [M - 2Br + 6]+ (100), 561 [M - 3Br + 4]+ (8), 533 [M - 3BrCO + 4]+ (11), 482 [M - 4Br + 4]+ (8), 373 [M - 5BrCO + 2]+ (9), 321 [M - 2Br + 3]2+ (17), 267.5 [M 3BrCO + 2]2+ (6). 2,2′,3,3′,5,5′,6,6′-Octabromodiphenyl Ether (BDE-202). Bromine (10 mL, 195 mmol) was added to 4,4′-diaminodiphenyl ether (3) (0.40 g, 2.00 mmol) and aluminum tribromide (5.6 g, 21.00 mmol) and the mixture was refluxed for 5 h. The subsequent reaction steps were performed as described above for BDE-198 with the following crude products obtained. Diazotization of the perbrominated crude product (1.54 g, 1.86 mmol) was carried out with boron trifluoride diethyl etherate (1.05 g, 7.42 mmol, 0.94 mL) in THF (10 mL) and 3-methylbutyl nitrite (1.31 g, 11.2 mmol, 1.31 mL). The diazonium salt obtained in an amount of 1.54 g (1.50 mmol) was dissolved in DMF (6 mL) and iron(II)sulfate heptahydrate VOL. 41, NO. 21, 2007 / ENVIRONMENTAL SCIENCE & TECHNOLOGY

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(1.25 g, 4.5 mmol) in DMF (6 mL) was used for the reduction. The product was purified on a silica gel column with n-hexane as the mobile phase and crystallized from acetonitrile/THF. Yield: 0.21 g, 0.26 mmol, 13%. Mp 239.5-241 °C. 1H NMR (DMSO-d6): δ ) 8.19 (s, 2H). 13C NMR: δ ) 152.50, 133.70, 126.80, 118.58 ppm. EIMS: m/z [ion] (rel. int. %) 802 [M + 8]+ (7), 642 [M - 2Br + 6]+ (100), 561 [M - 3Br + 4]+ (8), 533 [M - 3BrCO + 4]+ (12), 482 [M - 4Br + 4]+ (7), 373 [M 5BrCO + 2]+ (8), 321 [M - 2Br + 3]2+ (16), 267.5 [M - 3BrCO + 2]2+ (6). 2,2′,3,4,4′,5,6,6′-Octabromodiphenyl Ether (BDE-204), Pathway A. Bromine (5 mL, 98 mmol) was added to 3,5diaminodiphenyl ether (4) (0.43 g, 2.12 mmol) and aluminum tribromide (2.3 g, 8.53 mmol). The reaction mixture was refluxed for 5 h. The synthesis was continued as described above for BDE-198 with the following crude products obtained. Diazotization of the perbrominated crude product (1.63 g, 1.96 mmol) was carried out with boron trifluoride diethyl etherate (1.1 g, 7.84 mmol, 0.99 mL) in THF (10 mL) and 3-methylbutyl nitrite (1.38 g, 11.8 mmol, 1.58 mL). The diazonium salt obtained in an amount of 1.63 g (1.58 mmol) was dissolved in DMF (6 mL) and iron(II)sulfate heptahydrate (1.32 g, 4.7 mmol) was dissolved in DMF (6 mL) during the reduction. Purification was performed without preparative HPLC. Yield: 0.23 g, 0.28 mmol, 13%. Mp 197.5-198.5 °C. 1H NMR: δ ) 7.85 (s, 2H) ppm. 13C NMR: δ ) 151.63, 149.62, 136.91, 129.90, 125.76, 120.17, 118.12, 115.78 ppm. EIMS: m/z [ion] (rel. int. %) 802 [M + 8]+ (14), 642 [M - 2Br + 6]+ (100), 561 [M - 3Br + 4]+ (10), 533 [M - 3BrCO + 4]+ (13), 482 [M - 4Br + 4]+ (7), 452[M - 4Br + 4]+ (5), 373 [M 5BrCO + 2]+ (8), 321 [M- 2Br + 3]2+ (17). 2,2′,3,4,4′,5,6,6′-Octabromodiphenyl Ether (BDE-204), Pathway B. Bromine (5 mL, 98 mmol) was added to 3-aminodiphenyl ether (5) (0.38 g, 2.06 mmol) and aluminum tribromide (1.66 g, 6.22 mmol). The mixture was refluxed for 5 h. The synthesis was continued as described above for BDE-198 with the following crude products obtained. Diazotization of the perbrominated crude product (1.77 g, 1.98 mmol) was performed by boron trifluoride diethyl etherate (0.84 g, 5.94 mmol, 0.75 mL) in THF (6 mL) and 3-methylbutyl nitrite (0.93 mg, 7.92 mmol, 1.06 mL). The diazonium salt obtained in an amount of 1.77 g (1.78 mmol) was dissolved in DMF (6 mL) and iron(II)sulfate heptahydrate (1.48 g, 5.3 mmol) in DMF (6 mL) was added for the reduction. Purification was performed without preparative HPLC. Yield: 0.51 g, 0.64 mmol, 31%. 3,3′,5,5′-Tetrabromo-4,4′-diaminodiphenyl Ether (6). Bromine (2.0 mL, 40 mmol) was added to 4,4′-diaminodiphenyl ether (2.0 g, 10 mmol) in acetic acid (50 mL) at room temperature. The reaction was stirred at 35 °C for 5 min and then poured into ice-cold water (200 mL). The crude product was filtered off and purified on silica gel column with n-hexane/ethyl acetate (6:1) as the mobile phase. Yield: 3.7 g, 7.2 mmol, 72%. Mp 165-167 °C (Lit. 169.5-170 (33).1H NMR (CDCl3): δ ) 7.07 (s, 4H) ppm, 4.39 (s, 4H) ppm. 13C NMR (CDCl3): δ ) 148.86, 138.62, 122.49, 108.68 ppm. EIMS: m/z [ion] (rel. int. %), 516 [M + 4]+ (100), 435 [M - Br + 2]+ (8), 407 [M - BrCO + 2]+ (13), 355 [M - 2BrH + 2]+ (25), 266 [M - 2Br6CN2H]+ (33), 168 [M - 4BrCO]+ (9). 3,3′,4,4′,5,5′-Hexabromodiphenyl Ether (BDE-169). 3,3′,5,5′Tetrabromo-4,4′-diaminodiphenyl ether (1.03 g, 2.0 mmol) was suspended in acetonitrile (150 mL). The reaction was cooled to 0 °C and boron trifluoride diethyl etherate (0.76 mL, 6.0 mmol) was added. The reaction was stirred at 0 °C for 10 min (during which time the suspension was dissolved) and at room temperature for 60 min. 3-Methylbutyl nitrite (0.80 mL, 5.2 mmol) was added at 0 °C and the reaction was stirred for 60 min at 0 °C. Subsequently, the reaction mixture was cooled to -25 °C and poured into a mixture of copper (Ι) bromide (29 g, 0.2 mol) and copper (ΙΙ) bromide (54 g, 7462

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0.24 mol) in water (25 mL) at 0 °C and the reaction vessel was washed with acetonitrile (25 mL) in order to transfer all diazonium salt. The reaction mixture was stirred at 25 °C for 2 h, quenched by adding aqueous 5% sodium hydrogen carbonate (300 mL), and extracted with ethyl acetate (3 × 250 mL). The combined organic phases were concentrated to a volume of about 200 mL and washed with brine (3 × 200 mL). The product was isolated by recrystallization from THF/ acetonitrile. Yield: 0.83 g, 1.3 mmol 65%. Mp: 218-218.5 °C. 1 H NMR: δ ) 7.48 (s, 4H) ppm. 13C NMR: δ ) 156.77, 127.18, 124.48, 123.35 ppm. EIMS: m/z [ion] (rel. int.%), 644 [M + 6]+ (39), 563 [M - Br + 4]+ (7), 535 [M - BrCO + 4]+ (15), 484 [M - 2Br + 4]+ (76), 456 [M - 2BrCO + 4]+ (13), 403 [M - 3Br + 2]+ (94), 375 [M - 3BrCO + 2]+ (100), 324 [M - 4Br + 2]+ (35), 242 [M - 2Br + 2]2+ (40), 136 [M - 6BrCO]+ (5). 2,2′,3,3′,4,4′,5,5′-Octabromodiphenyl Ether (BDE-194). 3,3′,4,4′,5,5′-Hexabromodiphenyl ether (BDE-169) (0.64 g, 1.0 mmol) was added to a mixture of bromine (0.20 mL, 4.0 mmol) and iron powder (0.06 g, 1.0 mmol) in carbon tetrachloride (3.5 mL). The mixture was refluxed at 70 °C for 1.5 h and the residue was washed with aqueous 5% sodium bisulfite (5 mL), sodium hydroxide (1 M, 5 mL), water (5 mL), aqueous 5% sodium disulfite (5 mL), and water (5 mL). Finally, the product was recrystallized in THF/acetonitrile. Yield: 0.64 g, 0.80 mmol, 80%. Mp 221-222 °C. 1H NMR: δ ) 7.47 (s, 2H) ppm. 13C NMR: δ ) 153.72, 131.16, 125.76, 124.96, 123.60, 118.81 ppm. EIMS: m/z [ion] (rel. int. %), 802 [M - 4Br + 4]+ (6), 642 [M - 2Br + 6]+ (100), 482 [M - 4Br + 4]+ (6). 2,3′,4,5′,6-Pentabromo-3,4′-diaminodiphenyl Ether (7). Bromine (2.6 mL, 51 mmol) was added during 10 min to 3,4′-diaminodiphenyl ether (2.0 g, 10 mmol) in acetic acid (60 mL) at room temperature. The reaction was stirred at 35 °C for 1 h, during which time the product precipitated and the mixture was poured into ice-cooled water (200 mL). The crude product was filtered off and purified on silica gel column with n-hexane/THF (4:1) as the mobile phase. Yield: 4.8 g, 8.1 mmol, 81%. Mp 175-177 °C. 1H NMR (CDCl3): δ ) 7.67 (s, 1H), 6.92 (s, 2H), 4.74 (s, 2H), 4.30 (s, 2H) ppm. 13C NMR (CDCl3): δ ) 148.65, 148.30, 143.45, 137.93, 134.78, 119.05, 109.06, 105.22, 104.95, 104.39. EIMS: m/z [ion] (rel. int. %), 594 [M + 4]+ (47), 434 [M - 2Br + 2]+ (100). 2,3,3′,4,4′,5′,6-Heptabromodiphenyl Ether (BDE-191). This compound was prepared from 2,3′,4,5′,6-pentabromo-3,4′diaminodiphenyl ether (1.19 g, 2.0 mmol) following the procedure used for the synthesis of BDE-169 above. Yield: 0.83 g, 1.15 mmol 57%. Mp 228-228.5 °C. 1H NMR: δ ) 8.19 (s,1H), 7.27 (s, 2H) ppm. 13C NMR: δ ) 156.44, 149.43, 137.55, 129.66, 127.37, 124.48, 123.98, 121.98, 120.89, 118.19 ppm. EIMS: m/z [ion] (rel. int. %), 722 [M + 6]+ (50), 560 [M - 2Br + 4]+ (100). 2,2′,3,3′,4,4′,5,6′-Octabromodiphenyl Ether (BDE-196). Bromine (0.26 mL, 5.0 mmol) in carbon tetrachloride (5 mL) was added to BDE-191 (0.72 g, 1.0 mmol) and iron powder (60 mg, 1.0 mmol) in carbon tetrachloride (50 mL). The mixture was heated at 80 °C for 2 h after which bromine (0.26 mL, 5.0 mmol) in carbon tetrachloride (5 mL) was added and the mixture was heated for an additional 2 h at 80 °C. Carbon tetrachloride and bromine were evaporated by a gentle stream of nitrogen at 30 °C and the product residue was purified from polar compounds on a silica gel column with n-hexane as the mobile phase. Finally, the product was recrystallized in THF/acetonitrile. Yield: 0.77 g, 0.945 mmol, 94%. Mp 209209.5 °C. 1H NMR: δ ) 8.21 (s, 1H) ppm, 6.97 (s, 1H) ppm. 13C NMR: δ ) 153.68, 149.67, 137.55, 131.40, 129.71, 125.61, 124. 67, 123.68, 123.06, 118.39, 117.85, 116.42. EIMS: m/z [ion] (rel. int. %), 802 [M + 8]+ (47), 642 [M - 2Br + 6]+ (100), 533 [M - 3BrCO + 4]+ (6), 482 [M - 4Br + 4]+ (7), 321 [M - 2Br + 3]2+ (5).

Acknowledgments We are grateful to Ioannis Athanassiadis for his MS assistance. Financial support has been obtained from the EU R&D 6th framework programme for the program “FIRE” (QLRT-200100596). Financial support was also gained through the Swedish foundation for strategic environmental research (MISTRA) to the “News” programme.

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Received for review June 19, 2007. Accepted August 7, 2007. ES071496O

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