Environ. Sci. Technol. 1999, 33, 3033-3037
Synthesis and Characterization of 32 Polybrominated Diphenyl Ethers GO ¨ RAN MARSH,* JIWEI HU,† EVA JAKOBSSON, SARA RAHM, AND A˙ K E B E R G M A N Department of Environmental Chemistry, Stockholm University, SE-106 91 Stockholm, Sweden
Polybrominated diphenyl ethers (PBDEs) are widely used as additive flame retardants in, for example, textiles, computers, television sets, and other electrical appliances. PBDEs are ubiquitous environmental contaminants, present also in humans. The environmental levels of the PBDEs are, however, still in general lower than those of polychlorinated biphenyls (PCBs). However, while the levels of PCBs generally are decreasing, those of the PBDEs are increasing in, for example, human milk. In the present study 32 individual PBDE congeners were synthesized and characterized. Physicochemical parameters including melting points and UV, 1H NMR, and mass spectra are reported. Twenty-nine monobrominated to heptabrominated diphenyl ethers were synthesized by the coupling between four diphenyliodonium salts and nine phenolates. One tetrabromodiphenyl ether and two hexabromodiphenyl ethers were synthesized by bromination of two different PBDEs. Twenty-one of the PBDEs and two of the iodonium salts, 2,2′,4,4′-tetrabromodiphenyliodonium chloride and 3,3′,4,4′tetrabromodiphenyliodonium chloride, are to the authors’ knowledge described for the first time. These synthesized reference compounds will aid in the identification and quantification of PBDEs present in environmental samples and will allow further assessment of PBDE toxicity.
Introduction Polybrominated diphenyl ethers (PBDEs) are industrially produced and used as flame retardant additives in, for example, high-impact polystyrene, ABS, flexible polyurethane foam, textiles, wire and cable insulation, and electrical connectors. PBDEs are also used in many common goods such as computers, television sets, and household electrical appliances. Three types of commercial PBDEs find wide application, namely “pentaBDEs”, “octaBDEs”, and “decaBDE”. Each of these are mixtures of several PBDE congeners (1). The global world consumption of PBDEs was in 1992 estimated to be 40 000 tonnes/year, of which 75% consisted of the decaBDE product, 15% the octaBDE product, and 10% the pentaBDE product (2). PBDEs are today ubiquitous environmental contaminants (3-6), measurable in human blood plasma (7, 8) and human mothers’ milk (9). In Sweden the levels of PBDEs in human mothers’ milk are still lower than the levels of polychlorinated biphenyls (PCBs), but while the PCB levels are decreasing (10), those of the PBDEs have increased by a factor of >50 * Corresponding author phone: +46-8-162029; fax: +46-8-152561; e-mail:
[email protected]. † Present address: Department of Chemistry, University of Jyva¨skyla¨, P.O. Box 35, 40351 Jyva¨skyla¨, Finland. 10.1021/es9902266 CCC: $18.00 Published on Web 07/27/1999
1999 American Chemical Society
between 1972 and 1997 [i.e., from 72 to 4010 pg/g of lipid weight based on the sum of eight PBDE congeners (9)]. The dominating PBDE congener in biota is 2,2′,4,4′-tetraBDE (BDE-47) (3-7, 9). [Note: The individual PBDE congeners are numbered according to the PCB numbering system (11).] According to many tests PBDEs exhibit low apparent toxicity (1); however, recent data indicate that this substance class may be more harmful than previously believed. 2,2′,4,4′,5-PentaBDE (BDE-99) has been reported to induce learning disabilities in mice (12) analogous to those caused by 2,2′,5,5′-tetrachlorobiphenyl (CB-52), one of the most potent PCB congeners in this context (13). Furthermore, PBDE congeners have been shown to interfere with the Ah-receptor, exhibiting both agonist and antagonist activities (14). The aim of the present work was to synthesize and characterize a number of individual PBDE congeners and to acquire their basic physical chemical parameters such as melting points and UV, mass, and 1H NMR spectra. These PBDEs will aid in their identification and quantification in environmental samples and, furthermore, allow assessment of their toxicity. Mainly three routes for the synthesis of individual PBDEs have previously been described: (i) bromination of diphenyl ether (15); (ii) coupling of a phenolate with a bromobenzene according to the Ullmann diphenyl ether synthesis (15); and (iii) coupling of a diphenyliodonium salt with a bromophenolate (16). In the present work, the latter method was used for the preparation of most of the reported PBDEs.
Experimental Section Chemicals. Bromobenzene was purchased from BDH (Poole, U.K.). 2,5-Dibromoaniline, 1,2-dibromobenzene, and all phenols (except 2,5-dibromophenol) were obtained from Aldrich (Gillingham, U.K.). 2,5-Dibromophenol was prepared as described below. 1,3-Dibromobenzene was obtained from Lancaster Synthesis Ltd. (Morecambe, U.K.). Open silica gel chromatography was performed on Kieselgel 60 (Merck, 4063 µm particles) (Darmstadt, Germany). Instruments. Gas chromatography (GC) was performed on a Varian 3400 gas chromatograph. The gas chromatograph was equipped with a DB-5 megabore column, 9.3 m × 0.53 mm, 1.5 µm film thickness (J&W Scientific, Folsom, CA) and a FID. The temperature program was 80 °C for 2 min, raised at 20 °C min-1 to 280 °C, which was held for 20 min. Nitrogen was used as the carrier gas, and the temperature of the injector was 290 °C. Gas chromatography/mass spectrometry (GC/MS) was performed on a quadrupole TSQ 700 Finnigan MAT instrument. The Varian 3400 gas chromatograph was equipped with a DB-5 fused silica capillary column, 30 m × 0.25 mm, 0.025 mm film thickness (J&W Scientific, Folsom CA). The temperature program was 80 °C for 2 min, raised at 30 °C min-1 to 200 °C, raised at 5 °C min-1 to 320 °C, which was held for 10 min. Helium was used as the carrier gas, and the temperature of the injector was 260 °C. Electron ionization (EI) was used at an ion source temperature of 140 °C and an electron energy of 70 eV. 1H NMR spectra were recorded at room temperature in CDCl3 or DMSO-d6 with a JEOL EX270 instrument at 270 MHz and a digital resolution of 0.37 Hz. Melting points were determined with a Bu ¨ chi 353 apparatus. UV spectra were recorded in cyclohexane using a Hitachi U-3210 spectrophotometer. The absorbance was determined for two concentrations (4.6-14 and 67-330 µg/mL), giving absorptions for the λmax between 0.2 and 1.5. VOL. 33, NO. 17, 1999 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
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Synthesis. Diphenyliodonium bromide (I) was synthesized as previously described (17). Potassium iodate (4.3 g, 20 mmol) was dissolved in concentrated sulfuric acid (20 mL), and iodine (1.8 g, 7 mmol) was added at 15-20 °C. After 15 h of stirring, the iodyl sulfate was collected and then suspended in concentrated sulfuric acid (25 mL) at 5-10 °C. Acetic anhydride (15 mL) and benzene (20 mL, 225 mmol) were added, and the mixture was stirred at room temperature for 2 h. Water (200 mL) was added and the mixture was filtered. The filtrate was extracted three times with ethyl acetate (3 × 30 mL) and three times with diethyl ether (3 × 30 mL). The product was precipitated from the filtrate by the addition of sodium bromide (10 g, 100 mmol) in water (10 mL): yield, 7.0 g (19 mmol, 56%); mp 173-174 °C [lit. 246247 °C (18)]; 1H NMR (DMSO-d6) δ 8.23 (H2, H2′, H6, H6′, d, J ) 7.8 Hz), 7.66 (H4, H4′, t, J ) 7.3 Hz), 7.52 (H3, H3′, H5, H5′, t, J ) 7.8, 7.3 Hz). 4,4′-Dibromodiphenyliodonium chloride (II) was synthesized with only minor modification of methodology previously described (16, 19). A mixture of concentrated sulfuric acid (15 mL) and 30% fumic sulfuric acid (30 mL) was added to iodine (12.7 g, 50 mmol) under stirring. Then a mixture of concentrated sulfuric acid (4 mL), 65% fumic sulfuric acid (2 mL), and 100% fumic nitric acid (6.5 mL) was slowly added. The reaction mixture was stirred at 70-80 °C for 1.5 h, at which time yellow crystals of iodyl sulfate precipitated. The mixture was then cooled to 0 °C, and bromobenzene (40 g, 250 mmol) was slowly added. The mixture was stirred at 45 °C for 2 h and then cooled to 0 °C. Water (100 mL) was carefully added in small portions [Caution: Exothermic reaction!]. The nitrogen oxides were removed by introducing a gentle steam of nitrogen into the reaction solution. The product, a brown oil, was collected, dissolved in methanol, and crystallized as the chloride salt by dropwise addition of concentrated hydrochloric acid: yield, 10.7 g (23 mmol, 23%); mp 173-174 °C [lit. 212 °C (19)]; 1H NMR (DMSO-d3) δ 8.13 (H2, H2′, H6, H6′, d, J ) 8.2 Hz), 7.71 (H3, H3′, H5, H5′, d, J ) 8.2 Hz). 2,2′,4,4′-Tetrabromodiphenyliodonium chloride (III) synthesis was performed at two-fifths the scale for synthesis of compound II and with the addition of 1,3-dibromobenzene (25 g, 106 mmol) at 10-15 °C. The careful addition of water [Caution: Exothermic reaction!] at 5-10 °C resulted in a precipitation of the solid iodonium salt: yield, 16.6 g (26 mmol, 62%); mp 164-165 °C; 1H NMR (DMSO-d6) δ 8.34 (H6, H6′, d, J ) 8.4 Hz), 8.18 (H3, H3′, d, J ) 2.2 Hz), 7.17 (H5, H5′, dd, J ) 8.4, 2.2 Hz). 3,3′,4,4′-Tetrabromodiphenyliodonium chloride (IV) synthesis was performed as described above for the synthesis of compound III but with the addition of 1,2-dibromobenzene (25 g, 106 mmol): yield, 15.2 g (24 mmol, 57%); mp 188-189 °C; 1H NMR (DMSO-d6) δ 8.70 (H2, H2′, d, J ) 1.5 Hz), 8.13 (H6, H6′, dd, J ) 8.4 Hz, J ) 1.5 Hz,), 7.90 (H5, H5′, d, J ) 8.4 Hz). General Procedure for Synthesis of PBDEs. The phenol (2.5 mmol) with or without bromine substituents was dissolved in an aqueous solution (20 mL) of sodium hydroxide (0.1 g, 2.5 mmol). The diphenyliodonium salt (2.5 mmol) was added and the mixture refluxed. The time necessary to complete the reaction varied from 20 min to 1.5 h. For the synthesis of 2,2′,4,5′-tetraBDE (BDE-49) and 2,2′,3,4,4′,5,6-heptaBDE (BDE-181) 3.75 mmol of the diphenyliodonium salt was used. The PBDEs were generally extracted from the crude mixtures using diethyl ether (2 × 30 mL). However, BDE-181 and 2,3,3′,4,4′,5,6-heptaBDE (BDE-190) were extracted with dichloromethane because of their better solubility in this solvent. The combined organic phases were washed with water and then dried over sodium sulfate. The solution was filtered, the solvent was evaporated, and the product was purified on an open silica gel column with n-hexane as the mobile phase. 3034
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TABLE 1. Structures, Abbrevations, and Yields of the Synthesized PBDEs (Starting Materials of the PBDEs Synthesized via Iodonium Salt Coupling Are Included) PBDE no.a
structure
1 2 3 7 8 10 12 13 15 17 25 28 30 32 33 35 37 47 49 51 66 71 75 77 100 116 119 140 154 166 181 190
2342,42,4′2,63,43,4′4,4′2,2′,42,3′,42,4,4′2,4,62,4′,62′,3,43,3′,43,4,4′2,2′,4,4′2,2′,4,5′2,2′,4,6′2,3′,4,4′2,3′,4′,62,4,4′,63,3′,4,4′2,2′,4,4′,62,3,4,5,62,3′,4,4′,62,2′,3,4,4′,6′2,2′,4,4′,5,6′2,3,4,4′,5,62,2′,3,4,4′,5,62,3,3′,4,4′,5,6-
iodonium saltb
bromophenol
I I I I II I IV II II III III II I II IV IV IV III III III IV IV II
2342,422,6phenol 34232,42,4,62,62342,4 2,5 2,62,42,62,4,6-
III I IV
2,4,6penta2,4,6-
II III IV
pentapentapenta-
yield previously (%) reported in ref 44 35 18 35 17 37 23 17 18 39 58 16 25 23 58 45 35 43 87 52 55 43 23 95 36 17 8 20 14 10 11 5
21 15, 21 22, 23 24 25 25 16, 26 27 28
29, 30
30
a The PBDEs are numbered according to nomenclature used for the PCBs (11). b I, diphenyliodonium bromide; II, 4,4′-dibromodiphenyliodonium chloride; III, 2,2′,4,4′-tetrabromodiphenyliodonium chloride; IV, 3,3′,4,4′-tetrabromodiphenyliodonium chloride.
The PBDEs were finally purified from any trace amounts of dioxin-like contaminants, which may give erroneous results when used unpurified in toxicological studies, on an open column containing a mixture of activated charcoal and Celite with n-hexane as the mobile phase. Charcoal (0.2 g) and Celite (0.8 g) were used for each 100 mg of total amount of substance. 3,3′,4,4′-Tetrabromodiphenyl Ether (BDE-77). Bromine (0.38 mL, 7.4 mmol), dissolved in tetrachloromethane (60 mL), was slowly added to a stirred mixture of 3,3′,4-triBDE (BDE-35) (300 mg, 0.73 mmol) and iron powder (41 mg, 0.74 mmol) in tetrachloromethane (90 mL). The mixture was stirred at 50 °C for 2 h. Any residual bromine was reduced by the addition of 5% aqueous sodium bisulfite (2 × 50 mL). The product was purified as described above. 2,2′,3,4,4′,6′-Hexabromodiphenyl Ether (BDE-140) and 2,2′,4,4′,5,6′-Hexabromodiphenyl Ether (BDE-154). Bromine (9.1 µL, 0.18 mmol) was dissolved in tetrachloromethane (1 mL) and added to a mixture of 2,3′,4,4′,6-pentaBDE (BDE119) (100 mg, 0.18 mmol) and iron powder (10 mg, 0.18 mmol) in tetrachloromethane (10 mL). The mixture was stirred at 80 °C. The progress of the reaction was studied by GC (FID). After 1.5 h, ∼1% of BDE-119 remained and the reaction was stopped by the addition of 5% aqueous sodium bisulfite (10 mL). The organic layer was washed with water (3 × 10 mL) and dried over sodium sulfate. The product was purified as described above, but with the use of n-hexane/dichloromethane (9:1) as the mobile phase on the silica gel column. Two PBDE congeners were isolated and recrystallized from n-hexane.
TABLE 2. Melting Points (mp), UV Data, and MS Data of the Synthesized PBDEs PBDE no.
mp (°C)
UVa λ (nm) (log E)
MS (m/z, rel int %)
BDE-1 BDE-2 BDE-3 BDE-7 BDE-8 BDE-10 BDE-12 BDE-13 BDE-15 BDE-17 BDE-25 BDE-28 BDE-30 BDE-32 BDE-33 BDE-35 BDE-37 BDE-47 BDE-49 BDE-51 BDE-66 BDE-71 BDE-75 BDE-77 BDE-100 BDE-116 BDE-119 BDE-140 BDE-154 BDE-166 BDE-181 BDE-190
oil oil oil oil oil oil oil oil 56-56.5 oil oil 64-64.5 85-86 77-77.5 oil oil 48-49 78,5-79 oil 96-97 oil 134-135 134.5-135.5 94-95 97-98 199.5-200 86-87 180-181 142-143 183.5-184.5 156-157 197-197.5
200,b 269.8 (3.31), 276.8 (3.33) 200,b 271,6 (3.03), 277.5 (3.09), 283.3 (3.00) 200,b 268.1 (3.23), 271.6 (3.23), 278.6 (3.23), 290.3 (3.01) 205.2 (4.58), 269.5 (3.24), 276.9 (3.20), 286.4 (3.15), 295.0 (3.00) 202.0 (4.62), 275.2 (3.27), 281 (3.23) 205.0 (4.75), 262.0 (3.06), 268.7 (3.19), 275.2 (3.16) 204.8 (4.70), 268.9 (3.14), 278.6 (3.09), 285.5 (3.11), 294.2 (3.05) 200,b 275.3 (3.34), 282.9 (3.32) 200,b 273.7 (3.32), 281.7 (3.32), 289.7 (3.23) 203.2 (4.80), 275.5 (3.19), 282.1 (3.18) 293.2 (2.98) 203.2 (4.48), 274.4 (3.08), 281.2 (3.05) 201.4 (4.89), 274.4 (3.12), 281.6 (3.08) 210.4 (4.83), 268.7 (3.31), 275.1 (3.26), 289.9 (2.90) 204.6 (4.83), 279.2 (3.22), 287.4 (3.13) 203.8 (4.84), 267.8 (3.22), 275.3 (3.28), 283.9 (3.29), 292.5 (3.19) 207.4 (4.73), 274.6 (3.24), 283.9 (3.22), 292.8 (3.02) 203.4 (4.27), 276.6 (3.20), 284.0 (3.19) 204.4 (4.81), 278.6 (3.38), 285.1 (3.44), 293.4 (3.32) 202.6 (4.61), 281.3 (3.27), 284.1 (3.27), 288.5 (3.22) 211.8 (4.34), 283.9 (3.37), 292.8 (3.34) 205.8 (4.93), 279.5 (3.32), 284.9 (3.36), 292.3 (3.26) 205.4 (4.85), 282.9 (3.23), 291.1 (3.20) 210.8 (4.88), 279.9 (3.32), 286.7 (3.26) 202.6 (4.64), 285.6 (3.30), 294.1 (3.25) 210.6 (4.95), 282.9 (3.46), 292.2 (3.42) 225.6 (4.77), 267.9 (3.51), 274.7 (3.49) 209.2 (4.95), 282.3 (3.24), 290.9 (3.22) 213.2 (4.91) 286.1 (3.04), 296.0 (3.05) 211.4 (4.83) 289.2 (3.27), 298.3 (3.23) 226.4 (4.85) 271.2 (3.50), 277.9 (3.48), 285.4 (3.37) 227.6 (4.63), 283.1 (3.43), 291.6 (3.36) 226.8 (4.66), 274.4 (3.47), 282.8 (3.46), 291.0 (3.40)
M+, 48; (M - Br)+, 100 M+, 100; (M - Br)+, 25 M+, 100; (M - Br)+, 9 (M + 2)+, 30; (M - 2Br)+, 100 (M + 2)+, 41; (M - 2Br)+, 100 (M + 2)+, 22; (M - 2Br)+, 100 (M + 2)+, 100; (M - 2Br)+, 46 (M + 2)+, 100; (M - 2Br)+, 57 (M + 2)+, 100; (M - 2Br)+, 43 (M + 2)+, 84; (M - 2Br)+, 100 (M + 2)+, 30; (M - 2Br)+, 100 (M + 2)+, 94; (M - 2Br)+, 100 (M + 2)+, 41; (M - 2Br)+, 100 (M + 2)+, 75; (M - 2Br)+, 100 (M + 2)+, 43; (M - 2Br)+, 100 (M + 2)+, 100; (M - 2Br)+, 31 (M + 2)+, 100; (M - 2Br)+, 27 (M + 4)+, 86; (M - 2Br + 2)+, 100 (M + 4)+, 60; (M - 2Br + 2)+, 100 (M + 4)+, 64; (M - 2Br + 2)+, 100 (M + 4)+, 55; (M - 2Br + 2)+, 100 (M + 4)+, 46; (M - 2Br + 2)+, 100 (M + 4)+, 73; (M - 2Br + 2)+, 100 (M + 4)+, 100; (M - 2Br + 2)+, 22 (M + 4)+, 100; (M - 2Br + 2)+, 82 (M + 4)+, 33; (M - 2Br + 2)+, 100 (M + 4)+, 61; (M - 2Br + 2)+, 100 (M + 6)+, 38; (M - 2Br + 4)+, 100 (M + 6)+, 41; (M - 2Br + 4)+, 100 (M + 6)+, 47; (M - 2Br + 4)+, 100 (M + 6)+, 61; (M - 2Br + 4)+, 100 (M + 6)+, 36; (M - 2Br + 4)+, 100
a The λ b Due to measurement max value of the largest absorption is given first followed by λmax of other characteristic absorption bands values. difficulties near 200 nm, the λmax values of the largest absorption for the three monoBDEs, BDE-13, and BDE-15 are only approximate.
2,5-Dibromophenol. 2,5-Dibromoaniline was reacted at one-third of the scale described by Henley and Turner (20). The product was purified as described above for the heptaBDEs and with dichloromethane/n-hexane (2:1) as the mobile phase on the silica gel column. 2,5-Dibromophenol was obtained in 91% yield (7.3 g, 29.0 mmol): mp 72-73 °C [lit. 73-74 °C (20)]; 1H NMR (270 MHz, CDCl3) δ 7.31 (H3, d, J ) 8.4 Hz), 7.12 (H6, d, J ) 2.2 Hz), 6.95 (H4, dd, J ) 8.4, 2.2 Hz), δ 5.56 (OH, s).
Results Three monoBDEs, six diBDEs, eight triBDEs, six tetraBDEs, three pentaBDEs, one hexaBDE, and two heptaBDEs were all synthesized by the reaction between phenol or eight brominated phenols and the diphenyliodonium salt or three brominated diphenyliodonium salts. Three additional PBDE congeners, one tetra- and two hexaBDEs, were synthesized by bromination of BDE-35 and BDE-119, respectively. All PBDEs synthesized were at >98% purity, and 2,5-dibromophenol was >99% purity according to GC (FID) analysis. Structures, abbreviations, and yields for all synthesized PBDEs and starting materials are given in Table 1. Melting points, UV absorption, and mass spectrometry data are given for all PBDE congeners in Table 2. 1H NMR characteristics of the synthesized PBDEs are shown in Table 3. The syntheses of 2,5-dibromophenol, diphenyliodonium bromide, 4,4′-dibromodiphenyliodonium chloride, 2,2′,4,4′-tetrabromodiphenyliodonium chloride, and 3,3′,4,4′-tetrabromodiphenyliodonium chloride are described under Experimental Section. The physicochemical characteristics of these compounds are given there as well.
4,4′-Dibromodiphenyliodonium chloride, 2,2′,4,4′-tetrabromodiphenyliodonium chloride, and 3,3′,4,4′-tetrabromodiphenyliodonium chloride were prepared according to methods similar to those previously described for the synthesis of various diphenyliodonium chlorides (16, 19). Besides the bromodiphenyliodonium salts described above, 2,2′,5,5′-tetrabromodiphenyliodonium salt has previously been reported (16). The iodonium salts were coupled with phenols in aqueous solutions of sodium hydroxide according to the method of Nilsson et al. (16). This method was previously used for the preparation of polychlorinated diphenyl ethers (PCDEs) (17, 31) and also three PBDEs (16, 28). Two of these PBDEs, 4,4′-diBDE (BDE-15) (16) and 2,4,6triBDE (BDE-30) (28), have also been synthesized in this work. This reaction pathway has proven to be valuable for the preparation of a large number of PCDEs (17, 31). The method generates only one PCDE/PBDE congener, which facilitates the cleanup procedure. Other methods, such as the Ullmann ether synthesis or bromination (15), were based on previous experiences, known to give more complex reaction mixtures, resulting in a difficult cleanup. Taken together these considerations led to the selection of the iodonium salt pathway for the synthesis of most PBDEs presented in this study. However, the Ullmann ether synthesis and direct bromination of various PBDEs may be useful for the preparation of certain PBDEs.
Discussion
The yields of the pentaBDEs and higher brominated PBDEs, especially the heptaBDEs, synthesized via the iodonium salt coupling reaction are lower than those of PBDEs containing one to four bromine atoms (Table 1). More side reactions were observed when the penta-heptaBDEs were prepared in comparison to synthesis of mono-tetraBDEs.
The synthesis of diphenyliodonium bromide was performed according to the method of Nevalainen and Koistinen (17).
Seven of the brominated phenols were commercially available, whereas 2,5-dibromophenol was prepared from VOL. 33, NO. 17, 1999 / ENVIRONMENTAL SCIENCE & TECHNOLOGY
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TABLE 3. 1H NMR Chemical Shifts and 1H-1H Coupling Constants of the Synthesized PBDEs δ (from TMS)
PBDE no. BDE-1 BDE-2 BDE-3 BDE-7 BDE-8 BDE-10 BDE-12 BDE-13 BDE-15 BDE-17 BDE-25 BDE-28 BDE-30 BDE-32 BDE-33 BDE-35 BDE-37 BDE-47 BDE-49 BDE-51 BDE-66 BDE-71 BDE-75 BDE-77 BDE-100 BDE-116 BDE-119 BDE-140 BDE-154 BDE-166 BDE-181 BDE-190
7.63 (H3, dd, J ) 7.9, 1.6 Hz), 7.34 (H3′, H5′, t, J ) 8.6, 7.5 Hz), 7.25 (H5, dt, J ) 8.6, 7.5, 1.6 Hz), 7.11 (H4′, t, J ) 7.5 Hz), 7.01 (H4, t, J ) 7.9, 7.5, 1.5 Hz), 6.97 (H2′, H6′ d, J ) 8.6 Hz), 6.96 (H6, d, J ) 8.6, 1.5 Hz) 7.36 (H3′, H5′, t, J ) 8.3, 7.5 Hz), 7.22 (H4, dt, J ) 7.9, 2.2 Hz), 7.18 (H5, t, J ) 7.9, 7.7 Hz), 7.15 (H4′, t, J ) 7.5 Hz), 7.14 (H2, t, J ) 2.2 Hz), 7.02 (H2′, H6′, d, J ) 8.3 Hz), 6.93 (H6, dt, J ) 7.7, 2.2 Hz) 7.43 (H3, H5, d, J ) 9.2 Hz), 7.35 (H3′, H5′, t, J ) 8.1, 7.6 Hz), 7.12 (H4′, t, J ) 7.6 Hz), 7.00 (H2′, H6′, d, J ) 8.1 Hz), 6.88 (H2, H6, d, J ) 9.2 Hz) 7.77 (H3, d, J ) 2.2 Hz), 7.36 (H5, dd, J ) 8.8, 2,2 Hz), 7.35 (H3′, H5′, t, J ) 8.3, 7.6 Hz), 7.13 (H4′, t, J ) 7.6 Hz), 6.96 (H2′, H6′, d, J ) 8.3 Hz), 6.81 (H6, d, J ) 8.8 Hz) 7.64 (H3, dd, J ) 7.9, 1.6 Hz), 7.43 (H3′, H5′, d, J ) 9.2 Hz), 7.28 (H5, dt, J ) 8.1, 7.7, 1.6 Hz), 7.05 (H4, dt, J ) 7.9, 7.7, 1.5 Hz), 6.98 (H6, dd, J ) 8.1, 1.5 Hz), 6.83 (H2′, H6′, d, J ) 9.2 Hz) 7.61 (H3, H5, d, J ) 8.1 Hz), 7.30 (H3′, H5′, t, J ) 8.3, 7.5 Hz), 7.05 (H4′, t, J ) 7.5 Hz), 7.01 (H4, t, J ) 8.1 Hz), 6.81 (H2′, H6′, d, J ) 8.3 Hz) 7.53 (H5, d, J ) 8.8 Hz), 7.38 (H3′, H5′, t, J ) 8.5, 7.3 Hz), 7.25 (H2, d, J ) 2.9 Hz), 7.17 (H4′, t, J ) 7.3 Hz), 7.01 (H2′, H6′, d, J ) 8.5 Hz), 6.83 (H6, dd, J ) 8.8, 2.9 Hz) 7.46 (H3′, H5′, d, J ) 9.0 Hz), 7.24 (H4, dt, J ) 7.7, 1.8 Hz), 7.19 (H5, t, J ) 7.7 Hz), 7.13 (H2, t, J ) 1.8 Hz), 6.93 (H6, dt, J ) 7.7, 1.8 Hz), 6.90 (H2′, H6′, d, J ) 9.0 Hz) 7.44 (H3, H5, H3′, H5′, d, J ) 9.0 Hz), 6.88 (H2, H6, H2′, H6′, d, J ) 9.0 Hz) 7.78 (H3, d, J ) 2.2 Hz), 7.64 (H3′, dd, J ) 7.9, 1.8 Hz), 7.34 (H5, dd, J ) 8.8, 2.2 Hz), 7.28 (H5′, dt, J ) 8.1, 7.3, 1.8 Hz), 7.06 (H4′, dt, J ) 7.9, 7.3, 1.5 Hz), 6.89 (H6′, dd, J ) 8.1, 1.5 Hz), 6.66 (H6, d, J ) 8.8 Hz) 7.79 (H3, d, J ) 2.2 Hz) 7.41 (H5, dd, J ) 8.8, 2.2 Hz), 7.25 (H4′, dt, J ) 8.1, 2.2, 1.8 Hz), 7.19 (H5′, t, J ) 8.1, 8.0 Hz), 7.09 (H2′, t, J ) 2.2, 1.8 Hz), 6.88 (H6′, dt, J ) 8.0, 2.2, 1.8 Hz), 6.87 (H6, d, J ) 8.8 Hz) 7.78 (H3, d, J ) 2.3 Hz), 7.44 (H3′, H5′, d, J ) 8.8 Hz), 7.39 (H5, dd, J ) 8.5, 2.3 Hz), 6.84 (H6, d, J ) 8.5 Hz), 6.83 (H2′, H6′, d, J ) 8.8 Hz) 7.76 (H3, H5, s), 7.30 (H3′, H5′, t, J ) 8.6, 7.5 Hz), 7.06 (H4′, t, J ) 7.5 Hz), 6.80 (H2′, H6′, d, J ) 8.6 Hz) 7.61 (H3, H5, d, J ) 8.1 Hz), 7.40 (H3′, H5′, d, J ) 9.2 Hz), 7.03 (H4, t, J ) 8.1 Hz), 6.70 (H2′, H6′, d, J ) 9.2 Hz) 7.65 (H3′, dd, J ) 7.9, 1.8 Hz), 7.53 (H5, d, J ) 8.8 Hz), 7.32 (H5′, dt, J ) 8.1, 7.7, 1.8 Hz), 7.19 (H2, d, J ) 2.6 Hz), 7.10 (H4′, dt, J ) 7.9, 7.7, 1.5 Hz), 7.03 (H6′, dd, J ) 8.1, 1.5 Hz), 6.77 (H6, dd, J ) 8.8, 2.6 Hz) 7.57 (H5, d, J ) 8.8 Hz), 7.29 (H4′, dt, J ) 8.1, 1.8 Hz), 7.27 (H2, d, J ) 2.9 Hz), 7.22 (H5′, t, J ) 8.1, 7.7 Hz), 7.16 (H2′, t, J ) 2.2, 1.8 Hz), 6.94 (H6′, ddd, J ) 7.7, 2.2, 1.8 Hz), 6.84 (H6, dd, J ) 8.8, 2.9 Hz) 7.55 (H5, d, J ) 8.8 Hz), 7.47 (H3′, H5′, d, J ) 8.8 Hz), 7.24 (H2, d, J ) 2.6 Hz), 6.90 (H2′, H6′, d, J ) 8.8 Hz), 6.82 (H6, dd, J ) 8.8, 2.6 Hz) 7.79 (H3, H3′ d, J ) 2.2 Hz), 7.38 (H5, H5′, dd, J ) 8.8, 2.2 Hz), 6.71 (H6, H6′, d, J ) 8.8 Hz) 7.80 (H3, d, J ) 2.2 Hz), 7.50 (H3′, d, J ) 8.8 Hz), 7.41 (H5, dd, J ) 8.8, 2.2 Hz), 7.17 (H4′, dd, J ) 8.8, 2.2 Hz), 6.91 (H6′, d, J ) 2.2 Hz), 6.78 (H6, d, J ) 8.4 Hz) 7.78 (H3, d, J ) 2.2 Hz), 7.62 (H3′, H5′, d, J ) 8.1 Hz), 7.25 (H5, dd, J ) 8.8, 2.2 Hz), 7.05 (H4′, t, J ) 8.1 Hz), 6.26 (H6, d, J ) 8.8 Hz) 7.80 (H3, d, J ) 2.2 Hz), 7.55 (H5′, d, J ) 8.8 Hz), 7.43 (H5, dd, J ) 8.8, 2.2 Hz), 7.19 (H2′, d, J ) 2.9 Hz), 6.89 (H6, d, J ) 8.8 Hz), 6.77 (H6′, dd, J ) 8.8, 2.9 Hz) 7.62 (H3, H5, d, J ) 8.1 Hz), 7.51 (H5′, d, J ) 8.8 Hz), 7.09 (H2′, d, J ) 2.9 Hz), 7.05 (H4, t, J ) 8.1 Hz), 6.65 (H6′, dd, J ) 8.8, 2.9 Hz) 7.76 (H3, H5, s), 7.40 (H3′, H5′, d, J ) 9.2 Hz), 6.69 (H2′, H6′, d, J ) 9.2 Hz) 7.58 (H5, H5′, d, J ) 8.8 Hz), 7.27 (H2, H2′, d, J ) 2.9 Hz), 6.84 (H6, H6′, dd, J ) 8.8, 2.9 Hz) 7.78 (H3′, d, J ) 2.2 Hz), 7.77 (H3, H5, s), 7.26 (H5′, dd, J ) 8.8, 2.2 Hz), 6.27 (H6′, d, J ) 8.8 Hz) 7.32 (H3′, H5′, t, J ) 8.1, 7.4 Hz), 7.09 (H4′, t, J ) 7.4 Hz), 6.79 (H2′, H6′, d, J ) 8.1 Hz) 7.77 (H3, H5, s), 7.52 (H5′, d, J ) 8.8 Hz), 7.08 (H2′, d, J ) 2.9 Hz), 6.64 (H6′, dd, J ) 8.8, 2.9 Hz) 7.78 (H3′, H5′, s), 7.45 (H5, d, J ) 8.8 Hz), 6.24 (H6, d, J ) 8.8 Hz) 7.88 (H3, s), 7.79 (H3′, H5′, s), 6.58 (H6, s) 7.42 (H3′, H5′, d, J ) 9.2 Hz), 6.68 (H2′, H6′, d, J ) 9.2 Hz) 7.80 (H3′, d, J ) 2.2 Hz), 7.27 (H5′, dd, J ) 8.8, 2.2 Hz), 6.25 (H6′, d, J ) 8.8 Hz) 7.53 (H5′, d, J ) 8.8 Hz), 7.09 (H2′, d, J ) 2.9 Hz), 6.62 (H6′, dd, J ) 8.8, 2.9 Hz)
2,5-dibromoaniline as previously described (20), but it was isolated and purified differently. BDE-77 was prepared in high yield by bromination of BDE-35 using bromine as the bromination reagent, similar to the way Tolstaya et al. (30) brominated 3,3′-diBDE (BDE11) leading to BDE-77. BDE-140 and BDE-154 were prepared by bromination of BDE-119 using bromine as the bromination reagent. BDE-140 and BDE-154 coeluted to some extent on silica gel and were therefore only partly separated. To our knowledge, 21 of the PBDEs and 2 of the iodonium salts, 2,2′,4,4′-tetrabromodiphenyliodonium chloride and 3,3′,4,4′-tetrabromodiphenyliodonium chloride, are described here for the first time. All monoBDEs, most of the di- and triBDEs, and two tetraBDEs were oils at room temperature, whereas the majority of the tetraBDEs and higher brominated PBDEs were solids with melting points between 70 and 200 °C (Table 2). The UV spectra of the PBDEs showed the largest maximum absorbance between 200 and 230 nm. Highly brominated PBDEs had the largest maximum absorbance at longer 3036
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wavelengths. Characteristic absorption bands were observed for all PBDE congeners between 265 and 300 nm, with values that are 1 or 2 orders of magnitude lower than values at the largest absorption maxima. In the case of mass spectra data only the most abundant ions are given (Table 2). The major ions corresponded to the molecular ion (M+) or the loss of one (for the monoBDEs) or two bromine substituents (for the di-heptaBDEs). The molecular ion was the base peak of PBDEs with no bromine substituents in the ortho positions, whereas the base peak of ortho-brominated PBDE congeners corresponded to m/z (M - 2Br)+. The only exception to this rule was 2,2′,4,4′,6pentaBDE (BDE-100), which had the molecular ion as the base peak. Doubly charged ions were observed of an intensity up to 60% of the base peak in some of the PBDE mass spectra. 1H chemical shifts for the PBDE protons occur in the shift region δ 6.24-7.88 (Table 3). The 1H chemical shifts for orthohydrogens of tri-ortho-substituted PBDEs were significantly upfield. Similar observations have previously been reported for PCDEs (17, 32). This diamagnetic shielding of the ortho-
hydrogen in diphenyl ethers with three bulky ortho-substituents may partly be described as an inter-ring effect caused by the neighboring ring current due to the skew or near skew conformation with the ortho-hydrogen forced inside (33). Diamagnetic shielding was also clearly observed for the 2,6substituted PBDEs, but the effect was not as pronounced as for the PBDEs containing three ortho-bromine atoms. Most of the 32 individual PBDE congeners synthesized have already been used in several cases for identification and quantification of PBDEs in environmental samples (4, 6-9) as well as for toxicological studies (14, 34). Relative retention times, from four different GC columns, for 25 of the 32 synthesized PBDEs have been reported elsewhere (35). The synthesized PBDEs were together with the PBDEs prepared by O ¨ rn et al. (15) used for the identification of 11 major PBDE congeners (9 of them new) in the commercial pentaBDE product Bromkal 70-5DE (35). Five of the synthesized PBDE congeners have been identified as major PBDE constituents in environmental samples. Those are 2,4,4′triBDE (BDE-28), BDE-47, 2,3′,4,4′-tetraBDE (BDE-66), BDE100, and BDE-154 (6, 7, 9). Other PBDE congeners that have been identified in biota include BDE-99, 2,2′,4,4′,5,5′hexaBDE (BDE-153) (6, 7, 9), and 2,2′,3,4,4′,5′,6-heptaBDE (BDE-183) (8).
Acknowledgments We acknowledge Vlado Zorcec and Ioannis Athanasiadis for their assistance with mass spectrometry. We are grateful to Thomas Wehler for his expertise in NMR discussions. This study was funded by both the European Union R&D program “Environment and Climate” and the Swedish EPA.
Literature Cited (1) Environmental Health Criteria 162: Brominated Diphenyl Ethers; World Health Organization: Geneva, Switzerland, 1994. (2) Arias, P. Brominated diphenyloxides as flame retardants, Bromine based chemicals; Consultants report to the OECD: Paris, France, 1992; p 4. (3) Haglund, P. S.; Zook, D. R.; Buser, H.-R.; Hu, J. Environ. Sci. Technol. 1997, 31, 3281-3287. (4) Sellstro¨m, U.; Kierkegaard, A.; de Wit, C.; Jansson, B. Environ. Toxicol. Chem. 1998, 17, 1065-1072. (5) de Boer, J.; Wester, P. G.; Klamer, H. J. C.; Lewis, W. E.; Boon, J. P. Nature 1998, 394, 28-29. (6) Asplund, L.; Athanasiadou, M.; Sjo¨din, A.; Bergman, A° .; Bo¨rjeson, H. Ambio 1999, 28, 67-76. (7) Klasson Wehler, E.; Hovander, L.; Bergman, A° . Organohalgen Compd. 1997, 33, 420-425. (8) Sjo¨din, A.; Hagmar, L.; Klasson-Wehler, E.; Kronholm-Diab, K.; Jakobsson, E.; Bergman, A° . Environ. Health Perspect. 1999, 107, 643-648.
(9) Meironyte´, D.; Nore´n, K.; Bergman, A° . Jpn. J. Toxicol. Environ. Health (in press). (10) Nore´n, K.; Meironyte´, D. Organohalogen Compd. 1998, 38, 1-4. (11) Ballschmiter, K.; Mennel, A.; Buyten, J. Fresenius’ J. Anal. Chem. 1993, 346, 396-402. (12) Eriksson, P.; Jakobsson, E.; Fredriksson, A. Organohalogen Compd. 1998, 35, 375-377. (13) Eriksson, P.; Fredriksson, A. Organohalogen Compd. 1996, 29, 143-146. (14) Meerts, I. A. T. M.; Luijks, E. A. C.; Marsh, G.; Jakobsson, E.; Bergman, A° .; Brouwer, A. Organohalogen Compd. 1998, 37, 147150. (15) O ¨ rn, U.; Eriksson, L.; Jakobsson, E.; Bergman, A° . Acta Chem. Scand. 1996, 50, 802-807. (16) Nilsson, C.-A.; Norstro¨m, A° .; Hansson, M.; Andersson, K. Chemosphere 1977, 6, 599-607. (17) Nevalainen, T.; Koistinen, J. J. Environ. Sci. Technol. 1994, 28, 1341-1347. (18) Beringer, F. M.; Galton, S. A. J. Org. Chem. 1965, 30, 1930-1934. (19) Beringer, F. M.; Falk, R. A.; Karniol, M.; Lillien, I.; Masullo, G.; Mausner, M.; Sommer, E. J. Am. Chem. Soc. 1959, 81, 342-351. (20) Henley, R. V.; Turner, E. E. J. Chem. Soc. 1930, 928-940. (21) Sax, K. J.; Saari, W. S.; Mahoney, C. L.; Gordon, J. M. J. Org. Chem. 1960, 25, 1590-1595. (22) Krause, E.; Weinberg, K. Chem. Ber. 1929, 62, 2235-2241. (23) Olah, G. A.; Ohannesian, L.; Arvanaghi, M. Synthesis 1986, 10, 868-870. (24) Sharutin, V. V.; Zhidkov, V. V.; Muslin, D. V.; Liapina, N. Sh.; Fukin, G. K.; Zakharov, L. N.; Yanovsky, A. I.; Struchkov, Yu. T. Russ. Chem. Bull. 1995, 44, 931-936. (25) Kreisel, G.; Rudolph, G.; Schulze, D. K.-W.; Poppitz, W. Monatsh. Chem. 1992, 123, 1153-1161. (26) Le Fe`vre, R. J. W.; Saunders: S. L. M.; Turner, E. E. J. Chem. Soc. 1927, 1168-1173. (27) Fink, W. Helv. Chim. Acta. 1973, 56, 355-363. (28) Hu, J.; Kolehmainen, E.; Nevalainen, T.; Kauppinen, R. Chemosphere 1994, 28, 1069-1078. (29) Norstro¨m, A° .; Andersson, K.; Rappe, C. Chemosphere 1976, 5, 255-261. (30) Tolstaya, T. P.; Vanchikova, L. N.; Lisichkina, I. N. Bull. Acad. Sci. USSR Div. Chem Sci. 1984, 33, 1282-1285. (31) Garå, A.; Andersson, K.; Nilsson, C.-A.; Norstro¨m, A° . Chemosphere 1981, 10, 365-390. (32) Nevalainen, T.; Kolehmainen, E. Magn. Reson. Chem. 1994, 32, 480-486. (33) Montaudo, G.; Finocchiaro, P. J. Mol. Struct. 1972, 14, 53-59. (34) Meerts, I. A. T. M.; Marsh, G.; van Leeuwen-Bol, I.; Luijks, E. A. C.; Jakobsson, E.; Bergman, A° .; Brouwer, A. Organohalogen Compd. 1998, 37, 309-312. (35) Sjo¨din, A.; Jakobsson, E.; Kierkegaard, A.; Marsh, G.; Sellstro¨m, U. J. Chromatogr. A 1998, 822, 83-89.
Received for review February 25, 1999. Revised manuscript received June 7, 1999. Accepted June 8, 1999. ES9902266
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