Synthesis of polychlorinated biphenyls and their metabolites with a modified Suzuki-coupling

Article abstract of DOI:10.1016/j.chemosphere.2004.04.035

A modified procedure for the synthesis of polychlorinated biphenyls (PCBs) utilizing the Suzuki-coupling, a palladium-catalyzed cross-coupling reaction, is described. The coupling of (chlorinated) benzene boronic acids with bromochlorobenzenes, using Pd(dppf)₂Cl₂ (dppf=1,1 ^′-bis(diphenylphosphino)ferrocene) as the catalyst and aqueous sodium carbonate as the base, gave the desired PCB congeners in moderate to good yields. Eleven PCB congeners, including environmentally important PCB congeners and metabolites, were synthesized using this modified procedure. This new catalyst Pd(dppf)₂Cl₂ offers the advantage of being less air-sensitive and has a longer shelf life compared to Pd(PPh₄) ₄. Three new (di-)methoxylated PCB congeners were synthesized using the same procedure by either coupling a chlorinated benzene boronic acid with a bromo (di-)methoxybenzene or by coupling a (di-)methoxy benzene boronic acid with a chlorinated bromobenzene. The dimethoxylated PCB congeners were readily converted into the respective dihydroxylated PCB derivatives using boron tribromide in dichloromethane. This approach offers the advantage of high selectivity and moderate to good yields compared to conventional methods such as the Cadogan reaction and allows the use of less toxic starting materials.

Full text of DOI:10.1016/j.chemosphere.2004.04.035

Chemosphere 56 (2004) 735–744
www.elsevier.com/locate/chemosphere
Synthesis of polychlorinated biphenyls and their
metabolites with a modified Suzuki-coupling
Izabela Kania-Korwel , Sean Parkin , Larry W. Robertson a,*,
a,b
c
a
Hans-Joachim Lehmler
a
Department of Occupational and Environmental Health, College of Public Health, University of Iowa,
1
00 Oakdale Campus #219 IREH, Iowa City, IA 52242, USA
b
c
Department of Environmental Chemistry and Technology, University of Silesia,
Szkolna 9, Katowice 40-006, Poland
Department of Chemistry, University of Kentucky, Lexington, KY 40536, USA
Received 2 September 2003; received in revised form 2 February 2004; accepted 20 April 2004
Abstract
A modified procedure for the synthesis of polychlorinated biphenyls (PCBs) utilizing the Suzuki-coupling, a pal-
ladium-catalyzed cross-coupling reaction, is described. The coupling of (chlorinated) benzene boronic acids with
0
bromochlorobenzenes, using Pd(dppf) Cl
sodium carbonate as the base, gave the desired PCB congeners in moderate to good yields. Eleven PCB congeners,
including environmentally important PCB congeners and metabolites, were synthesized using this modified procedure.
2
2
(dppf ¼ 1,1 -bis(diphenylphosphino)ferrocene) as the catalyst and aqueous
This new catalyst Pd(dppf)
2 2
Cl offers the advantage of being less air-sensitive and has a longer shelf life compared to
Pd(PPh . Three new (di-)methoxylated PCB congeners were synthesized using the same procedure by either coupling a
4 4
)
chlorinated benzene boronic acid with a bromo (di-)methoxybenzene or by coupling a (di-)methoxy benzene boronic
acid with a chlorinated bromobenzene. The dimethoxylated PCB congeners were readily converted into the respective
dihydroxylated PCB derivatives using boron tribromide in dichloromethane. This approach offers the advantage of
high selectivity and moderate to good yields compared to conventional methods such as the Cadogan reaction and
allows the use of less toxic starting materials.
ꢀ
2004 Elsevier Ltd. All rights reserved.
Keywords: PCB; Methoxylated PCB; Synthesis; Palladium; Cross-coupling
1
. Introduction
resulted in their worldwide distribution. Physicochemi-
cal characteristics, such as lipophilicity and stability
towards biological and thermal degradation, have re-
sulted in their accumulation in the food chain, raising
concerns about human health effects. Animal and epi-
demiological studies have implicated PCBs in a number
of human disease processes such as carcinogenesis and
arteriosclerosis. However, possible mechanisms of PCB
toxicity are still poorly understood, partly because
technical PCB products contain a complex mixture of
the possible 209 PCB derivatives or congeners. Studies
of the biological effects of PCBs as well as studies of
Polychlorinated biphenyls (PCBs) were manufac-
tured for a large number of technical applications
including for use in transformers and capacitors (Han-
sen, 1999; Robertson and Hansen, 2001). Their wide-
spread use and their persistence in the environment have
*
Corresponding author. Tel.: +1-319-335-4554; fax: +1-319-
3
35-4290.
E-mail address: larry-robertson@uiowa.edu (L.W. Robert-
son).
0
045-6535/$ - see front matter ꢀ 2004 Elsevier Ltd. All rights reserved.
doi:10.1016/j.chemosphere.2004.04.035

736
I. Kania-Korwel et al. / Chemosphere 56 (2004) 735–744
their chemical transport, degradation and remediation
greatly benefit from the availability of single congeners.
This situation is further complicated by the fact that
PCBs are metabolized in the environment as well as in
vivo to hydroxy- and sulfur-containing metabolites
spectroscopy. The IR spectra were obtained using a
1
Nicolet Magna-IR 560 Spectrometer ESP. The H and
1
3
CNMR spectra were recorded on a Varian VXR-400S
NMR Spectrometer by using CDCl (Cambridge Iso-
3
tope Laboratories, Andover, MA) as solvent and TMS
(tetramethylsilane) as internal standard. Combustion
analysis of all new compounds was performed by
Atlantic Microlab (Atlanta, GA). If not stated other-
wise, a Thermal Analysis 2920 differential scanning
instrument equipped with a refrigerated cooling system
(RSC) of a Perkin Elmer DSC 7 were used to measure
the melting points. Samples were heated at a rate of 10ꢁ/
min from 20 to 230 ꢁC and the onset of the main phase
transition was determined as reported previously (Le-
hmler et al., 2001). The analytical data of all compounds
are in agreement with their proposed structure as well as
literature data (Safe and Hutzinger, 1972; Welti and
Sissons, 1972; Wilson, 1975; Hutzinger et al., 1983;
Yanagisawa et al., 1986, 1987). The purity of all PCB
congeners and methoxy PCBs was analyzed with a
Hewlett Packard 5890 A Gas Chromatograph equipped
with a HP-1 (Methyl Silicone Gum) column (Hewlett
Packard, Avondale, PA) and determined based on rel-
ative peak area. The following conditions were used for
the gas chromatographic analysis: injector: 255 ꢁC,
detector (FID): 300 ꢁC, starting temperature: 40 ꢁC, final
temperature: 245 ꢁC, heating rate: 10 ꢁC/min. In addi-
tion, the GC–MS analysis of all compounds was per-
formed by the Mass Spectrometry Facility of the
University of Kentucky (Lexington, KY). Caution:
PCBs and their metabolites are reasonably anticipated
to be human carcinogens and should therefore be han-
dled in an appropriate manner. All phenols and anisoles
have a high vapor pressure and should be handled in a
fume hood.
(
Letcher et al., 2000). Many questions remain regarding
the biological and toxic effects of PCBs and their
metabolites, largely because these compounds are diffi-
cult to synthesize in large quantities for biological
studies.
We recently published the straightforward synthesis
of several PCB congeners (Lehmler and Robertson,
2
001b) and various (di-)methoxylated and (di-)hydroxy-
lated PCB metabolites via the Suzuki-coupling (Bauer
et al., 1995; McLean et al., 1996; Lehmler and Robert-
son, 2001a). This cross-coupling reaction between an
aryl boronic acid and an aryl bromide (Suzuki, 1999)
was conducted in the presence of tetrakis(triphenyl-
phosphine) palladium(0) and aqueous sodium carbonate
in toluene/ethanol at 80 ꢁC for 12 h. This approach has
significant advantages over conventional methods com-
monly employed for the synthesis of individual PCB
congeners such as the Cadogan (Cadogan et al., 1962) or
Ullmann (Fanta, 1974) coupling. Advantages include
the formation of a single product in a single step in high
yields. At the same time no highly toxic byproducts such
as dibenzofurans are formed during the reaction (Moron
et al., 1973). One drawback of the conventional Suzuki-
coupling is the tetrakis(triphenylphosphine) palla-
dium(0) catalyst itself which, in our hands, appears to be
difficult to store over periods of several month and
causes the formation of various side products (Lehmler
and Robertson, 2001b). We therefore investigated
0
Pd(dppf)
2
Cl
2
(dppf ¼ 1,1 -bis(diphenylphosphino)ferro-
cene) as a catalyst for the synthesis of individual PCB
congeners using the Suzuki-coupling. This catalyst
apparently can be stored without any problems even
over extended periods of time. At the same time we
streamlined the clean-up step of the reaction with the
goal of reducing the potential exposure of laboratory
personnel to PCBs and of minimizing the generation of
PCB-containing hazardous wastes.
2.1. General procedure for the synthesis of PCBs and PCB
derivatives
Sodium carbonate (5 ml, 2 M aq.) was added to a
solution of a chlorinated bromo- or iodobenzene (5
0
mmol) and Pd(dppf)
2
Cl
2
(dppf ¼ 1,1 -bis(diphenylphos-
This modified procedure has been utilized to syn-
thesize eleven important PCB congeners such as PCB 77
and PCB 118 as well as selected methoxylated and
hydroxylated PCB congeners. Methoxylated PCB
congeners are of interest as analytical standards for PCB
metabolism studies while hydroxylated PCB congeners
were synthesized to be used in various in vitro and in
vivo toxicity studies.
phino)ferrocene) (0.18 mg) in 1,4-dioxane (20 ml). A
solution of a chlorobenzene boronic acid (5 mmol) in
ethanol (10 ml) was added slowly to the solution of the
bromo or iodobenzene under a nitrogen atmosphere.
The reaction mixture was heated under reflux for 12–16
h. The reaction mixture was allowed to cool to room
temperature and Alumina (20 to 40 g, Alumina
adsorption 80–200 mesh, Fisher Scientific, Pittsburg,
PA) was added. The solvent was removed under reduced
pressure and the resulting powder was filtered through
an Alumina plug (ꢀ70–100 g) with 150–250 ml n-hex-
anes as eluent to yield the desired PCB congener.
Methoxylated PCBs were eluted with 150–250 ml n-
hexanes-ethyl acetate (9:1 v/v). The crude PCB deriva-
2
. Materials and methods
All PCB congeners and PCB metabolites were char-
13
acterized by H and C NMR, FT-IR and GC–MS
1

I. Kania-Korwel et al. / Chemosphere 56 (2004) 735–744
737
tives were purified either by recrystallization or column
chromatography as described previously (Bauer et al.,
Elemental Analysis Calcd. for C12
2.74; found: C 56.21, H 2.74.
H
7
C
3
: C 55.94, H
1
2
7
1
995; Lehmler and Robertson, 2001b).
0 0
.1.5. 2,3 ,4 ,5-Tetrachlorobiphenyl (3e)
2
.1.1. 2,6-Dichlorobiphenyl (3a)
1
1
H-NMR (CDCl
0
3
, 400 MHz) d 7.22–7.28 (m, 3H, H-
H-NMR (CDCl
.38–7.49 (m, 5H).
3
, 400 MHz) d 7.19–7.28 (m, 3H),
0
0
4
,6,6 ), 7.38 (m, 1H, H-3), 7.47–7.50 (m, 2H, H-2 ,6 ).
13
C-NMR (CDCl
CH), 130.22 (CH), 130.69, 130.84 (CH), 131.16 (CH),
3
, 100 MHz) d 128.68 (CH), 129.27
1
3
C-NMR (CDCl
3
, 100 MHz) d 128.00 (2 · CH),
(
28.05 (CH), 128.18 (2 · CH), 128.97 (CH), 129.47
1
31.22 (CH), 132.44, 132.52, 132.85, 137.90, 139.48.
EI-MS m=z (relative intensity, %): 290 (78,
(
2 · CH), 134.92, 136.94, 139.48.
EI-MS m=z (relative intensity, %): 222 (97,
ꢁþ
C
12
H
6
Cl ), 220 (55, M–Cl
ꢂ1
2
), 150 (23, M-4Cl).
IR (KBr pellet) [cm ]: 1456, 1360, 1139, 1103, 1029,
4
ꢁ
þ
C
12
H
8
Cl ), 186 (11, M-HCl), 152 (100, M–Cl
ꢂ1
2
).
IR (KBr pellet) [cm ]: 1557, 1437, 1423, 1191, 788,
2
881, 820, 811, 613.
Elemental Analysis Calcd. for C12
2.07; found: C 49.59, H 2.09.
7
3
2
77, 759, 697.
Elemental Analysis Calcd. for C12
.62; found: C 64.79, H 3.74.
6 4
H Cl : C 49.34, H
8 2
H Cl : C 64.58, H
0 0
.1.6. 3,3 ,4,4 -Tetrachlorobiphenyl (3f)
2
0
.1.2. 2,4,4 -Trichlorobiphenyl (3b): (Lehmler and Rob-
1
H-NMR (CDCl
J ¼ 2:0 Hz, 2H, H-6,6 ), 7.50 (d, J ¼ 8:4 Hz, 2H, H-
3
, 400 MHz) d 7.34 (dd, J ¼ 8:4 Hz,
ertson, 2001b)
0
1
H-NMR (CDCl
H, H-6), 7.30 (dd, J ¼ 8:4 Hz, J ¼ 2:0 Hz, 1H, H-5),
.33 (AA XX system, 2H, H-3 ,5 ), 7.40 (AA XX sys-
3
, 400 MHz) d 7.23 (d, J ¼ 8:4 Hz,
0
1
0
5
,5 ), 7.60 (d, J ¼ 2:0 Hz, 2H, H-2,2 ).
1
7
3
C-NMR (CDCl , 100 MHz) d 126.14 (CH), 128.78
3
0
0
0
0
0
0
(
CH), 130.94 (CH), 132.44, 133.20, 138.68.
EI-MS m=z (relative intensity, %): 290 (92,
0
0
tem, 2H, H-2 ,6 ), 7.48 (d, J ¼ 2:0 Hz, 1H, H-3).
1
3
C-NMR (CDCl , 100 MHz) d 127.26 (CH), 128.41
3
ꢁ
þ
C
12
H
6
Cl ), 220 (46, M–Cl
ꢂ1
2
).
IR (KBr pellet) [cm ]: 1462, 1453, 1134, 818.
4
(
2 · CH), 129.81 (CH), 130.66 (2 · CH), 131.88 (CH),
1
33.16, 134.06, 136.63, 137.83.
EI-MS m=z (relative intensity, %): 256 (100,
Elemental Analysis Calcd. for C12
.07; found: C 49.37, H 1.98.
6 4
H Cl : C 49.34, H
2
ꢁ
þ
þ
ꢂ1
þ
C
12
H
7
Cl ), 186 (65, M –Cl
2
), 150 (26, M –Cl
3
).
IR (KBr pellet) [cm ]: 1465, 1003, 877, 841, 808,
3
0
2
.1.7. 2,4,4 ,5-Tetrachlorobiphenyl (3g)
1
7
35, 542, 443.
0
0
3
H-NMR (CDCl , 400 MHz) d 7.31 (AA XX system,
0
0
0
0
0
2H, H-3 ,5 ), 7.38 (s, 1H, H-6), 7.39 (AA XX system,
2
.1.3. 2,4 ,5-Trichlorobiphenyl (3c)
1
0 0
2H, H-2 ,6 ), 7.56 (s, 1H, H-3).
H-NMR (CDCl
J ¼ 8:4 Hz, 1H, H-4), 7.30 (d, J ¼ 2:4 Hz, 1H, H-6),
3
, 400 MHz) d 7.25 (dd, J ¼ 2:4 Hz,
1
3
C-NMR (CDCl
3
, 100 MHz) d 128.56 (2 · CH),
0
0
0
0
130.53 (2 · CH), 131.21, 131.27 (CH), 132.12 (CH),
132.34, 134.55, 135.52, 139.08.
7
.34 (AA XX system, 2H, H-3 ,5 ), 7.38 (d, J ¼ 8:4 Hz,
H, H-3), 7.40 (AA XX system, 2H, H-2 ,6 ).
0
0
0
0
1
1
3
EI-MS m=z (relative intensity, %): 290 (76,
C-NMR (CDCl
3
, 100 MHz) d 128.44 (2 · CH),
ꢁ
þ
þ
ꢂ1
þ
C
12
H
6
Cl ), 220 (40, M –Cl
2
), 150 (11, M –Cl
4
).
IR (KBr pellet) [cm ]: 1455, 1142, 1084, 1036, 1014,
1
28.79 (CH), 130.61 (2 · CH), 130.73, 130.96 (CH),
31.11 (CH), 132.69, 134.26), 136.49, 140.69.
4
1
8
91, 869, 835, 736, 681, 622, 558, 491, 454, 423.
Elemental Analysis Calcd. for C H Cl : C 49.34, H
2.07; found: C 49.19, H 1.99.
EI-MS m=z (relative intensity, %): 256 (100,
ꢁ
þ
C
12
H
7
Cl ), 186 (82, M–Cl
ꢂ1
2
).
IR (KBr pellet) [cm ]: 1497, 1456, 1098, 1025, 1012,
12
6
4
3
8
2
2
7
28, 818, 586, 427.
Elemental Analysis Calcd. for C12
.74; found: C 56.01, H 2.81.
0
H
7
C
3
: C 55.94, H
2.1.8. 2,3 ,4,6-Tetrachlorobiphenyl (3h)
1
H-NMR (CDCl
), 7.21–7.23 (m, 1H, H-6 ), 7.37–7.39 (m, 2H, H-2 ,4 ),
3
, 400 MHz) d 7.08–7.11 (m, 1H, H-
0
0
0
0
5
7.40 (s, 2H, H-3,5).
.1.4. 2,4,5-Trichlorobiphenyl (3d)
1
13
H-NMR (CDCl
.44 (s, 1H, H-6), 7.58 (s, 1H, H-3).
3
, 400 MHz) d 7.38–7.48 (m, 5H),
3
C-NMR (CDCl , 100 MHz) d 127.80 (CH), 128.13
(2 · CH), 128.60 (CH), 129.63 (CH), 129.66 (CH),
134.21, 134.39, 135.36, 136.77, 137.51.
1
3
C-NMR (CDCl
3
, 100 MHz) d 128.52 (2 · CH),
1
28.56 (CH), 129.41 (2 · CH), 131.26, 131.39 (CH),
31.54, 132.16, 132.57 (CH), 137.49, 140.57.
EI-MS m=z (relative intensity, %): 290 (76,
ꢁ
þ
1
C
12
H
6
Cl ), 220 (61, M–Cl
ꢂ1
2
), 185 (12, M–Cl
3
).
IR (neat) [cm ]: 1575, 1430, 1367, 1183, 1079, 841,
4
EI-MS m=z (relative intensity, %): 256 (100,
ꢁ
þ
þ
ꢂ1
þ
C
12
H
7
Cl ), 186 (55, M –Cl
2
), 150 (41, M –Cl
IR (KBr pellet) [cm ]: 1454, 1442, 1088, 1045, 886,
3
).
800, 698, 663, 576, 497.
Elemental Analysis Calcd. for C12
2.07; found: C 49.69, H 2.20.
3
6 4
H Cl : C 49.34, H
7
58, 694, 679, 601, 435.

738
I. Kania-Korwel et al. / Chemosphere 56 (2004) 735–744
0
2
.1.9. 2,4,4 ,6-Tetrachlorobiphenyl (3i) EI-MS m=z (relative intensity, %): 282 (100,
1
0
0
ꢁþ
H-NMR (CDCl
0
3
, 400 MHz) d 7.17 (AA XX system,
H, H-3 ,5 ), 7.43 (s, 2H, H-3,5), 7.44 (AA XX system,
C
14
H
12Cl
2
O
), 267 (39, M–CH
ꢂ1
3
), 239 (60), 204 (98).
IR (KBr pellet) [cm ]: 3449, 1605, 1502, 1466, 1242,
2
0
0
0
0
2
2
0
H, H-2 ,6 ).
1
1141, 1030, 807, 647.
Elemental Analysis Calcd. for C14
H 4.27; found C 59.16, H 4.14.
3
C-NMR (CDCl
3
, 100 MHz) d 128.15 (2 · CH),
12 2 2
H O Cl : C 59.36,
1
1
28.69 (2 · CH), 130.98 (2 · CH), 134.25, 134.50, 135.42,
37.01.
EI-MS m=z (relative intensity, %): 290 (100,
0
0
ꢁþ
4
12 6 2
H Cl ), 254 (2, M-HCl), 220 (50, M–Cl ), 150 (17,
2.1.13. 2 ,5 -Dichloro-3,4-dihydroxybiphenyl (6)
m.p. ¼ 132 ꢁC.
C
4
M–Cl ).
1
3 3
H-NMR (CD COCD , 400 MHz) d 6.79 (dd,
ꢂ1
IR (KBr pellet) [cm ]: 1542, 1444, 1098, 1020, 1001,
54, 797, 736, 574.
J ¼ 8:0 Hz, J ¼ 2:0 Hz, 1H, H-6), 6.92 (d, J ¼ 8:0 Hz,
8
2
2
1
H, H-5), 6.96 (d, J ¼ 2:4 Hz, 1H, H-2), 7.34 (dd,
Elemental Analysis Calcd. for C12
.07; found: C 49.53, H 2.04.
6 4
H Cl : C 49.34, H
0
J ¼ 2:4 Hz, J ¼ 8:4 Hz, 1H, H-4 ), 7.36 (dd, J ¼ 0:4 Hz,
0
J ¼ 2:4 Hz, 1H, H-6 ), 7.49 (dd, J ¼ 0:8 Hz, J ¼ 8:4 Hz,
0
1
H, H-3 ).
1
0
0
.1.10. 2,3,3 ,4 ,5-Pentachlorobiphenyl (3j)
1
3
3 3
C-NMR (CD COCD , 100 MHz) d 116.01 (CH),
H-NMR (CDCl
0
3
, 400 MHz) d 7.20 (dd, J ¼ 2:4 Hz,
1
1
1
17.32 (CH), 121.94 (CH), 128.97 (CH), 130.68, 131.61,
31.87 (CH), 132.21 (CH), 133.13, 143.15, 145.65,
46.32.
0
1
7
H, H-2 ), 7.22 (dd, J ¼ 8:4 Hz, J ¼ 2:4 Hz, 1H, H-6 ),
.47 (d, J ¼ 2:4 Hz, 1H, H-6), 7.49 (d, J ¼ 2:4 Hz, 1H,
0
H-4), 7.50 (d, J ¼ 8:4 Hz, 1H, H-5 ).
EI-MS m=z (relative intensity, %): 398 (21,
1
3
C-NMR (CDCl
CH), 129.64, 129.73 (CH), 130.28 (CH), 130.97 (CH),
3
, 100 MHz) d 128.47 (CH), 129.14
ꢁþ
þ þ
2
18 2 2 3
H24Cl O Si ), 383 (6, M –CH ), 310 (11, M –
C
(
3
Si(CH )), 73 (100).
1
32.54, 132.71, 132.86, 134.59, 137.70, 141.07.
EI-MS m=z (relative intensity, %): 324 (60,
ꢂ1
IR (KBr pellet) [cm ]: 3499, 1621, 1560, 1584, 1523,
1513, 1442, 1386, 1329, 1300, 1208, 1097, 1028, 923, 874,
ꢁ
þ
C
12
H
5
Cl ), 254 (38, M–Cl
ꢂ1
2
).
IR (KBr pellet) [cm ]: 1543, 1474, 1413, 1360, 1136,
5
8
15, 799, 774, 642, 550.
1
1
2
032, 868, 820, 623.
Elemental Analysis Calcd. for C12
.54; found: C 44.01, H 1.61.
0
0
H
5
Cl
5
: C 44.13, H
2.1.14. 3 ,4 ,-Dichloro-2,3-dimethoxybiphenyl (8)
1
H-NMR (CDCl , 400 MHz) d 3.61 (s, 1H, –OCH ),
.91 (s, 1H, –OCH
3
3
3
3
), 6.90 (dd, J ¼ 2:0 Hz, J ¼ 8:0 Hz,
0
0
0
.1.11. 2,3 ,4,4 ,5-Pentachlorobiphenyl (3k)
1
1H, H-6), 6.96 (dd, J ¼ 2:0 Hz, J ¼ 8:4 Hz, 1H, H-4 ),
0
H-NMR (CDCl
J ¼ 2:0 Hz, 1H, H-6 ), 7.42 (s, 1H, H-6), 7.51 (d, J ¼ 2:0
3
, 400 MHz) d 7.26 (dd, J ¼ 8:0 Hz,
7.11 (dd, J ¼ 8:0 Hz, J ¼ 8:0 Hz, 1H, H-5 ), 7.41 (dd,
0
J ¼ 2:0 Hz, J ¼ 8:8 Hz, 1H, H-6), 7.47 (d, J ¼ 8:8 Hz,
1H, H-5), 7.65 (d, J ¼ 2:4 Hz, 1H, H-6).
0
0
Hz, 1H, H-2 ), 7.52 (d, J ¼ 8:0 Hz, 1H, H-5 ), 7.61 (s,
1
3
1
H, H-3).
1
3 3
C-NMR (CDCl , 100 MHz) d 55.93 (–OCH ),
3
C-NMR (CDCl
3
, 100 MHz) d 128.60 (CH), 130.34
CH), 131.09 (CH), 131.16, 131.40 (CH), 132.03 (CH),
60.68 (–OCH ), 112.26 (CH), 122.05 (CH), 124.30 (CH),
3
(
128.70 (CH), 129.98 (CH), 131.07 (CH), 131.18, 132.04,
133.44, 138.16, 146.41, 153.18.
1
32.60, 132.84, 132.93, 136.94, 137.86.
EI-MS m=z (relative intensity, %): 322 (62,
EI-MS m=z (relative intensity, %): 282 (83,
ꢁ
þ
ꢁþ
C
12
H
5
Cl ), 254 (29, M–HCl), 218 (5, M–HCl–Cl
2
), 184
C H Cl O ), 267 (32, M–CH ), 239 (100, M–C H O).
ꢂ1
5
14 12
2
2
3
2
3
(
8, M–Cl
IR (KBr pellet) [cm ]: 3084, 1453, 1145, 1091, 925,
77.
Elemental Analysis Calcd. for C12
.54; found: C 44.31, H 1.50.
4
).
IR (KBr pellet) [cm ]: 1578, 1454, 1265, 1117, 1034,
1004, 878, 793, 676.
Elemental Analysis Calcd. for C H O Cl : C 59.36,
ꢂ1
8
1
2
3
1
4
12
2
2
H
5
Cl
5
: C 44.13, H
H 4.27; found: C 59.09, H 4.36.
0
0
0
0
.1.12. 2 ,5 -Dichloro-3,4-dimethoxybiphenyl (5)
1
2.1.15. 3 ,4 -Dichloro-2,3-dihydroxybiphenyl (9)
m.p. ¼ 123 ꢁC.
H-NMR (CDCl
.93 (s, 3H, –OCH
3
, 400 MHz) d 3.91 (s, 3H, –OCH
3
),
1
), 6.92 (d, J ¼ 8 Hz, 1H, H-5), 6.96
H-NMR (CDCl
J ¼ 2:4 Hz, 1H, H-6), 6.90 (‘‘t’’, J ¼ 8:0 Hz, 1H, H-5),
6.93 (dd, J ¼ 8:0 Hz, J ¼ 2:4 Hz, 1H, H-3), 7.41 (dd,
3
, 400 MHz) d 6.86 (dd, J ¼ 8:0 Hz,
3
(
dd, J ¼ 2 Hz, J ¼ 8 Hz, 1H, H-6), 6.98 (d, J ¼ 2 Hz,
0
1
7
H, H-2), 7.22 (dd, J ¼ 2:4 Hz, J ¼ 8:4 Hz, 1H, H-4 ),
0
0
.34 (d, J ¼ 2:4 Hz, 1H, H-6 ), 7.38 (d, J ¼ 8:4 Hz, 1H,
J ¼ 8:0 Hz, J ¼ 2:0 Hz, 1H, H-6 ), 7.55 (d, J ¼ 8:0 Hz,
0
0
0
H-3 ).
1H, H-5 ), 7.67 (d, J ¼ 2:0 Hz, 1H, H-2 ).
1
3
13
C-NMR (CDCl
5.92 (–OCH ), 110.72, 112.54, 121.72, 128.12, 130.74,
30.85, 130.98, 131.10, 132.45, 141.65, 148.43, 148.89.
3
, 100 MHz) d 55.85 (–OCH
3
),
3
C-NMR (CDCl , 100 MHz) d 115.40 (CH), 121.18
5
1
3
(CH), 122.17 (CH), 126.47, 128.54 (CH), 130.91 (CH),
131.15 (CH), 132.02, 133.09, 137.31, 140.88, 143.97.

I. Kania-Korwel et al. / Chemosphere 56 (2004) 735–744
739
ꢂ1
EI-MS m=z (relative intensity, %): 398 (15,
IR (KBr pellet) [cm ]: 2829, 1498, 1469, 1463, 1224,
1037.
Elemental Analysis Calcd. for C16
6.62; found: C 70.02, H 6.59.
ꢁþ
þ þ
2
18 2 2 3
C H24Cl O Si ), 383 (8, M –CH ), 310 (8, M –
Si(CH
3
)
4
), 73 (100).
H
18 4
O : C 70.04, H
ꢂ1
IR (KBr pellet) [cm ]: 3464, 1552, 1384, 1255, 1164,
085, 678, 509.
1
2
.2. Crystal structure analysis
0
2
.1.16. 3,4 -Dichloro-4-methoxybiphenyl (11)
1
0
0
H-NMR (CDCl
3
, 400 MHz) d 3.98 (s, 3H, –OCH
3
),
X-ray diffraction data of 2,2 ,5,5 -tetramethoxybi-
0
0
6
.99 (d, J ¼ 8:4 Hz, 1H, H-5), 7.39 (AA XX system, 2H,
phenyl (12) were collected at 173 K on a Nonius kap-
paCCD diffractometer from an irregular block-shaped
crystal. Raw data were integrated, scaled, merged and
corrected for Lorentz-polarization effects using the
HKL-SMN package (Otwinowski and Minor, 1997).
The structure was solved by direct methods and differ-
ence Fourier (Sheldrick, 1997). Refinement was carried
0
0
H-3 ,5 ), 7.41 (dd, J ¼ 8:4 Hz, J ¼ 2:4 Hz, 1H, H-6),
0
0
0
0
7
1
.45 (AA XX system, 2H, H-2 ,6 ), 7.57 (d, J ¼ 2:4 Hz,
H, H-2).
1
3
3 3
C-NMR (CDCl , 100 MHz) d 56.25 (–OCH ),
1
1
1
12.29 (CH), 122.91, 126.13 (CH), 127.92 (2 · CH),
28.69 (CH), 128.98 (2 · CH), 133.29, 133.40, 137.99,
54.62.
2
out against F by weighted full-matrix least-squares
EI-MS m=z (relative intensity, %): 252 (100,
(Sheldrick, 1997). Hydrogen atoms were found in dif-
ference maps but subsequently placed at calculated
positions and refined using a riding model. Non-
hydrogen atoms were refined with anisotropic displace-
ment parameters. Atomic scattering factors were taken
from the International Tables for Crystallography
ꢁ
þ
C
13
H
11OCl ), 237 (96, M–CH
ꢂ1
3
), 209 (47, M–C
IR (KBr pellet) [cm ]: 3434, 1600, 1486, 1291, 1063,
2
H
3
O).
2
8
08.
Elemental Analysis Calcd. for C13
H 3.98; found C 61.91, H 3.93.
2
H10OCl : C 61.66,
(
Wilson, 1992). Further details of the crystal structure
0
0
analysis are available from the Cambridge Structural
Database.
2
.1.17. 2,2 ,5,5 -Tetramethoxybiphenyl (12)
m.p. ¼ 96–97 ꢁC.
1
3 3
H-NMR (CDCl , 400 MHz) d 3.73 (s, –OCH , 6H),
3
.78 (s, –OCH
3
, 6H), 6.83–6.88 (m, 4H), 6.91 (d, J ¼ 8:4
0
Hz, d, J ¼ 0:8 Hz, 2H, H-6, H-6 ).
3. Results and discussion
1
3
C-NMR (CDCl
3
, 100 MHz) d 55.67 (2 · –OCH
3
),
56.44 (2 · –OCH
1
3
), 112.40 (2 · CH), 113.34 (2 · CH),
The effects of different reaction solvents, reaction
temperatures, bases, and reaction times were investi-
gated to optimize the reaction conditions for the Suzuki-
17.08 (2 · CH), 128.56, 151.24, 153.26.
EI-MS m=z (relative intensity, %): 274 (100,
ꢁ
þ
).
C
16
H
18
O
2 2
coupling using Pd(dppf) Cl as a catalyst (Scheme 1).
4
R2
R1
R '
R '
R2
R1 R1'
R '
1
2
2
Pd(ppdf)Cl2,
2
M Na CO ,
dioxane
2
3
R3
X
+
(HO) B
R '
R3
R '
2
3
3
R4
R5
R '
R '
R4
R5 R5'
R '
5
4
4
1
a-h
2a-c
' = R
' = Cl
3
' = Cl
' = Cl
3a-k
1
1
a
b
c
d
e
f
X = Br; R
X = Br; R
X = Br; R
1
1
1
= R
= R
= R
5
3
4
= Cl
= Cl
= Cl
2a
2b
2c
2d
R
1
3
2
2
' = R
2
3
' = R
4
' = R
5
' = H
3a
R
R
R
R
R
R
R
R
R
R
1
1
1
1
1
2
1
1
1
1
= R
= R
= R
= R
= R
= R
= R
= R
= R
= R
5
3
4
3
4
3
3
3
3
3
= Cl
R
R
R
3b
3c
3d
3e
3f
3g
3h
= R
= R
= R
= R
= R
= R
= R
= R
= R
3
3
4
2
2
4
5
5
5
' = Cl
' = Cl
= Cl
1
1
1
1
1
1
' = R
X = I; R
X = I; R
X = I; R
X = I; R
X = I; R
1
2
1
1
1
= R
= R
= R
= R
= R
3
3
3
3
2
= R
= Cl
= R
= R
= R
4
= Cl
' = R
' = R
3
' = Cl
' = Cl
4
5
4
= Cl
= Cl
= Cl
3
g
h
= R
= R
= R
= R
3
' = Cl
' = Cl
' = Cl
' = Cl
2
3
3
3
3
i
h
Scheme 1. Synthesis of PCB congeners using the modified Suzuki-coupling reaction. See Table 1 for the respective boronic acids and
0
chloro bromo- or chloro iodobenzenes. R
n
and R ¼ H if not stated otherwise.
n

740
I. Kania-Korwel et al. / Chemosphere 56 (2004) 735–744
The effect of different reaction conditions is illustrated
using the synthesis of 2,4,5-trichlorobiphenyl (3d) as an
example in Table 1. The choice of solvent is of great
importance and apparently influences the purity and
yield of the (crude) product significantly. In contrast to
the classical catalyst used for Suzuki-coupling reactions,
In addition to using a different catalyst, we also
modified the clean-up step of the Suzuki-coupling with
the goal of minimizing exposure of laboratory personnel
and of reducing the generation of highly contaminated,
PCB hazardous wastes. Our previously published pro-
cedure for the Suzuki-coupling (Bauer et al., 1995; Le-
hmler and Robertson, 2001a,b) calls for hydrogen
peroxide to destroy excess benzene boronic acid. With
some boronic acids this deboronation step offers the
advantage that a volatile benzene derivative is formed
which can be removed with the solvent under reduced
pressure, while inorganic boronic acids salts are re-
moved from the reaction mixture by extraction with
sodium hydroxide. Unfortunately most chlorobenzenes
are not volatile and can not easily be removed under
reduced pressure. Because the properties, i.e. polarity, of
chlorobenzenes are similar to the properties of PCBs, it
is also difficult to remove these side products of the
deboronation by column chromatography, thus requir-
ing (several) recrystallization(s) of the product. Instead,
excess benzene boronic acids can be easily removed by
coating the crude reaction mixture on Alumina and,
subsequently, eluting the product from the dry adsor-
bent using hexanes as eluent. This workup also avoids
3 4 2 2
Pd(PPh ) , Pd(dppf) Cl is not soluble in nonpolar sol-
vents such as toluene or benzene. However, it is soluble
in polar solvents such as 1,4-dioxane, THF and DMF.
Reactions performed in DMF and THF, especially when
CsF was employed as a base (Wright et al., 1994), re-
sulted in a high percentage of impurities (usually about
2
0% based on peak area) and, in all cases, significant
amounts of starting material were present, even after
reaction times of 2 days. The purification of product
obtained in DMF and THF was therefore tedious and
several recrystallizations were required to obtain purities
above 98%. Moderate to good yields (36–77%, see Ta-
bles 1 and 2) were obtained when the reaction was
performed in 1,4-dioxane using aqueous sodium car-
bonate as base. Only low yields of 2,4,5-trichlorobi-
phenyl (3d) were obtained with CsF (3–15%, see Table
1
), which is frequently used as a base in Suzuki reactions
Wright et al., 1994).
(
Table 1
Effect of different reaction conditions on the yield of 2,4,5-trichlorobiphenyl (3d)
Solvent
Temperature [ꢁC]
Base
CsF
Time [h]
Yield [%]
THF
DMF
80
65
49
18
17
24
49
40
15
9
Na
2
CO
3
3
DMF
DMF
65
CsF
CsF
CsF
15
3
100
100
100
Dioxane
Dioxane
3
52
Na
2
CO
Table 2
Synthesis of PCBs and methoxylated PCBs using modified Suzuki-coupling
Bromo- or
iodo-benzene
Boronic acid
Product
Melting point
[ꢁC]
Melting point [ꢁC]
(Bolgar et al., 1995)
Yield
[%]
a
1
1
1
1
1
1
1
1
1
1
1
4
1
1
a
a
b
c
d
c
e
d
f
2a
2b
2b
2a
2c
2c
2b
2d
2b
2c
2c
2e
7a
2b
3a
3b
3c
3d
3e
3f
3g
3h
3i
Oil
56
35–36
58–59
64.5–65
77–78
104–105
180–181
127–129
52–54
62–63
70–71
111–113
–
36
42
61
52
68
69
16
11
64
77
56
69
77
41
64
80
101
179
130
Oil
68
f
g
d
3j
99
3k
5
111
80
i
8
11
88
105
–
0
–
Purified by two column chromatography steps, first on deactivated Alumina and then on Alumina activated at 400 ꢁC.

I. Kania-Korwel et al. / Chemosphere 56 (2004) 735–744
741
OMe
OH
MeO
Br
MeO
HO
Cl
Pd(ppdf)Cl2,
2M Na2CO3
dioxane
BBr3,
MeO
4
+
CH Cl
2
2
Cl
Cl
(
HO) B
2
Cl
Cl
5
6
2e
Cl
Scheme 2. Synthesis of a dihydroxylated PCB metabolite by the coupling of a chlorobenzene boronic acid with a bromo dimeth-
oxybenzene, followed by demethylation.
the aqueous extraction step employed to remove inor-
ganic salts. The product is obtained in moderate to good
yields and in good purities (>95%) with this modified
clean-up procedure (Table 2). The final purification was,
in most cases, a single recrystallization step yielding the
desired PCB in >99% purity as determined by GC. A
variety of PCB congeners, including environmentally
important congeners, such as PCB 28, PCB 77 and PCB
from a toxicological as well as from a regulatory point of
view. We are therefore particularly interested in
improving the availability of PCB congeners with mul-
tiple ortho substituents. Using this modified Suzuki-
coupling we were able to synthesize PCBs with two
ortho chlorine substituents in one phenyl ring (i.e., a 2,6-
dichloro substitution pattern) in good yields, for exam-
ple 3g and 3h (Scheme 1). However, we were unable to
extend the Suzuki-coupling to the synthesis of congeners
with ortho chlorine substituents in both phenyl rings, i.e.
1
synthesized using Pd(dppf) Cl in 1,4-dioxane and so-
18 (Hansen, 1999; Robertson and Hansen, 2001), were
2
2
0
dium carbonate as base (Table 2). These reaction con-
ditions can be easily used to synthesize large quantities
a 2,2 -dichloro substitution pattern.
Methoxylated PCBs are frequently employed as GC
standards for PCB metabolism studies (Bergman et al.,
1994), while hydroxylated PCBs are needed for various in
situ and in vitro toxicity studies (Srinivasan et al., 2001;
Tampal et al., 2002; van den Hurk et al., 2002). The
modified Suzuki-coupling procedure was therefore
(
e.g., >10 g) of a desired PCB congener.
PCB congeners with multiple (i.e., 3 or 4) ortho
chlorine substituents have mechanisms of toxicity dis-
tinctively different from dioxin-like congeners (Hansen,
1
999). There is increasing interest in these compounds
Cl
MeO
MeO
HO
Cl
Br
Pd(ppdf)Cl2,
BBr3,
2
M Na CO ,
dioxane
1
+
i
2
3
HO
CH Cl
2
2
MeO
OMe
(
HO) B
Cl
Cl
2
Cl
Cl
7
8
9
Scheme 3. Synthesis of a dihydroxylated PCB metabolite by the coupling of a dimethoxy benzene boronic acid with a chloro-
bromobenzene, followed by demethylation.

742
I. Kania-Korwel et al. / Chemosphere 56 (2004) 735–744
Cl
Cl
Pd(ppdf)Cl2,
2
M Na CO ,
dioxane
2
3
MeO
Br
+
(HO) B
Cl
MeO
Cl
2
10
2b
11
Scheme 4. Synthesis of 4-methoxylated PCB congeners.
Cl
Br
MeO
MeO
MeO
Pd(ppdf)Cl2,
Pd(ppdf)Cl2,
2
M Na CO
dioxane
1
a
Cl
2
3
2
M Na CO3
dioxane
2
OMe
OMe
MeO
Cl
+
Cl
MeO
(HO) B
2
12
7c
OMe
Scheme 5. Coupling of di-ortho chlorinated bromobenzenes with mono-ortho methoxy benzene boronic acids.
0
0
Fig. 1. Molecular structure of 2,2 ,5,5 -tetramethoxybiphenyl
12).
0
0
(
Fig. 2. Packing of 2,2 ,5,5 -tetramethoxybiphenyl (12) mole-
cules.
applied to the synthesis of methoxylated and hydroxyl-
ated PCB derivatives. Dimethoxylated PCBs were syn-
thesized by coupling of a bromo dimethoxybenzene (e.g.,
from the Alumina with hexanes-ethylacetate (9:1 v/v)
instead of hexanes. The modified Suzuki-coupling can
also be employed to synthesize PCB metabolites similar
to the ones found in human plasma, as illustrated for one
methoxylated standard (11) in Scheme 4.
4) with a chlorinated benzene boronic acid 2 (Scheme 2)
or by coupling of a (chlorinated) bromobenzene 1 with a
dimethoxybenzene boronic acid such as 7 (Scheme 3). In
both approaches the desired dimethoxy PCB was eluted

I. Kania-Korwel et al. / Chemosphere 56 (2004) 735–744
743
We investigated the coupling of 2,5-dimethoxyben-
zene boronic acid 7c with bromo-2,6-dichlorobenzene 1a
Bolgar, M., Cunningham, J., Cooper, R., Kozloski, R.,
Hubball, J., Miller, D.P., Crone, T., Kimball, H., Janooby,
A., Miller, B., Fairless, B., 1995. Physical, spectral and
chromatographic properties of all 209 individual pcb
congeners. Chemosphere 31, 2687–2705.
(
Scheme 5). We were unable to obtain the desired tri-
0
0
ortho substituted 2 ,6 -dichloro-2,5-dimethoxybiphenyl,
which is in agreement with our previous observations
that the reaction conditions employed are not suitable
for the synthesis of PCBs with one ortho-chlorine
Cadogan, J.I.G., Roy, D.A., Smith, D.M., 1962. An alterna-
tive to the Sandmeyer reaction. J. Chem. Soc. C, 1249–
1
250.
Fanta, P.E., 1974. The Ullmann synthesis of biaryls. Synthesis,
–21.
0
substituent in each phenyl ring (i.e., a 2,2 -dichloro sub-
0
0
stitution pattern). Instead, small quantities of 2,2 , 5,5 -
tetramethoxybiphenyl 12, the homocoupling coupling
product of 2,5-dimethoxybenzene boronic acid 7c, were
isolated. The structure of this product was confirmed by
NMR, IR and GC–MS as well as a crystal structure
analysis. A thermal ellipsoid plot and the molecular
packing of the tetramethoxy biphenyl 12 are shown in
Figs. 1 and 2, respectively. In contrast, we were never
able to detect or isolate the corresponding homocoupling
product of an ortho substituted chlorobenzene boronic
acid. At this point we can not explain this observation
but most likely steric and/or electronic effects prevent the
homocoupling of the chlorinated boronic acids.
9
Hansen, L.G., 1999. The Ortho Side of PCBs: Occurrence and
disposition. Kluwer Academic Publishers, Boston.
Hutzinger, O., Safe, S., Zitko, V., 1983. The Chemistry of
PCB’s. Robert E. Krieger Publishing Company, Malabar.
Lehmler, H.-J., Oyewumi, M.O., Jay, M., Bummer, P.M., 2001.
Behavior of partially fluorinated carboxylic acids at the air–
water interface. J. Fluorine Chem. 107, 141–146.
Lehmler, H.-J., Robertson, L.W., 2001a. Synthesis of hydrox-
ylated PCB metabolites with the Suzuki-coupling. Chemo-
sphere 45, 1119–1127.
Lehmler, H.-J., Robertson, L.W., 2001b. Synthesis of poly-
chlorinated biphenyls using the Suzuki-coupling. Chemo-
sphere 45, 137–143.
In summary, the modified Suzuki reaction described
herein allows the straightforward synthesis of a large
variety of PCB derivatives in good to moderate yields.
Letcher, R.J., Klasson-Wehler, E., Bergman, A., 2000. Methyl
sulfone and hydroxylated metabolites of polychlorinated
biphenyls. In: Paasivirta, J. (Ed.), The Handbook of
Environmental Chemistry, vol. 3, Part k. New Types of
Persistent Halogenated Compounds, Springer Verlag, Ber-
lin, Heidelberg, pp. 315–359.
2 2
The Pd(dppf) Cl catalyst, although more expensive,
apparently offers the advantage of an improved stability
during storage and lowers the occurrence of side
reactions. The improved clean-up procedure eliminates
the deboronation as well as the aqueous extraction step
without significantly lowering the reaction yield or
affecting the purity of the product, thus reducing exposure
of laboratory personnel during work-up and minimizing
generation of PCB contaminated hazardous wastes.
McLean, M.R., Bauer, U., Amaro, A.R., Robertson, L.W.,
1
996. Identification of catechol and hydroquinone meta-
bolites of 4-monochlorobiphenyl. Chem. Res. Toxicol. 9,
59–164.
1
Moron, M., Sundstr o€ m, G., Wachtmeister, C.A., 1973. Poly-
chlorinated biphenyls. VI. 2,3,7,8-tetrachlorodibenzofuran,
0
0
0
a critical byproduct in the synthesis of 2,2 ,4,4 ,5,5 -hexa-
chloro-biphenyl by the Ullmann reaction. Acta Chem.
Scand. 27, 3121–3122.
Acknowledgements
Otwinowski, Z., Minor, W., 1997. Processing of X-ray diffrac-
tion data collected in oscillation mode. In: Carter, C.W. Jr.,
Swet, R.M. (Eds.), Methods in Enzymology, vol. 276:
Macromolecular crystallography, Part A. Academic Press.
Robertson, L.W., Hansen, L.G., 2001. Recent Advances in the
Environmental Toxicology and Health Effects of PCBs.
University Press of Kentucky, Lexington.
The authors would like to thank Drs. Bummer
University of Kentucky, Lexington, USA) and Flana-
(
gan (University of Iowa, Iowa City, USA) for access to
the DSC instruments. The project was supported by
grant number P42 ES 07380 from the National Institute
of Environmental Health Sciences, NIH. Its contents are
solely the responsibility of the authors and do not nec-
essarily represent the official views of the NIEHS or
EPA. I.K.K. gratefully acknowledges the support of a
Fulbright Junior Research Grant and a Kosciuszko
Foundation Grant.
Safe, S., Hutzinger, O., 1972. The mass spectra of polychlori-
nated biphenyls. J. Chem. Soc. Perkin Trans. I, 686–
691.
Sheldrick, G.M., 1997. Shelx97––programs for crystal structure
solution and refinement. University of Gottingen, Germany.
Srinivasan, A., Lehmler, H.-J., Robertson, L.W., Ludewig, G.,
2
001. Production of DNA strand breaks in vitro and
reactive oxygen species in vitro and in HL-60 cells by PCB
metabolites. Toxicol. Sci. 60, 92–102.
References
Suzuki, A., 1999. Recent advances in the cross-coupling
reactions of organoboron derivatives with organic electro-
philes. J. Organomet. Chem. 576, 147–168.
Bauer, U., Amaro, A.R., Robertson, L.W., 1995. A new
strategy for the synthesis of polychlorinated biphenyl
metabolites. Chem. Res. Toxicol. 8, 92–95.
Tampal, N., Lehmler, H.-J., Espandiari, P., Malmberg, T.,
Robertson, L.W., 2002. Glucuronidation of hydroxylated
polychlorinated biphenyls (PCBs). Chem. Res. Toxicol. 15,
1259–1266.
ꢀ
Bergman, A., Klasson-Wehler, E., Kuroki, H., 1994. Selective
retention of hydroxylated PCB metabolites in blood.
Environ. Health Perspect. 102, 464–469.

744
I. Kania-Korwel et al. / Chemosphere 56 (2004) 735–744
van den Hurk, P., Kubiczak, G.A., Lehmler, H.J., James, M.O.,
002. Hydroxylated polychlorinated biphenyls as inhibitors
nated biphenyls. J. Am. Chem. Soc. 97, 3573–
3578.
2
of the sulfation and glucuronidation of 3-hydroxy-
benzo[a]pyrene. Environ. Health Perspect. 110, 343–348.
Welti, D., Sissons, D., 1972. The proton chemical shifts of
polychlorinated biphenyls. Org. Mag. Res. 4, 309–319.
Wilson, A.J.C. (Ed.), 1992. International Tables for Crys-
tallography, vol. 3. Kluwer Academic Publishers, Dordr-
echt.
Wright, S.W., Hageman, D.L., McClure, L.D., 1994. Fluorine-
mediated boronic acid coupling reactions. J. Org. Chem. 59,
6095–6097.
13
Yanagisawa, M., Hayamizu, K., Yamamoto, O., 1986. C
NMR shifts of chlorinated biphenyls. J. Mag. Res. 24,
1013–1014.
Yanagisawa, M., Hayamizu, K., Yamamoto, O., 1987.
1
H
Wilson, N.K., 1975. Carbon-13 nuclear magnetic resonance.
C shieldings and spin–lattice relaxation times in chlori-
NMR parameters of chlorinated biphenyls. J. Mag. Res. 25,
184–186.
13