7468
S.N. Joshi et al. / Tetrahedron 67 (2011) 7461e7469
159 (15); HRMS m/z: calculated for C6H4NCl2I2 [MþH] 413.7805;
6.94 (s, 2H), 5.57 (s, 1H, eOH); 13C NMR (100 MHz, CDCl3):
d/ppm
found 413.7774.
156.0, 137.1, 135.3, 132.7, 132.4, 131.4, 130.5, 129.7, 128.5, 115.4; mass
spectrum m/z (relative abundance %): 306 (Mꢄþ, 75), 270 (5), 235
(5); HRMS m/z: calculated for C12H6OCl4 [M] 305.9167, found
305.9177.
4.3. Synthesis of PCB derivatives
4.3.1. Synthesis of 4,40,6-trichloro-2-methoxybiphenyl 6a. A mixture
of 2c (0.45 g, 1.5 mmol), 4-chlorophenylboronic acid (5a) (0.47 g,
4.4. X-ray crystal structure analysis
3.0 mmol),
22.5 mol),
bis(dibenzylideneacetone)
palladium
(20 mg,
m
2-dicyclohexylphosphino-20,60-dimethoxybiphenyl
X-ray diffraction data were collected at 90.0 (2) K on either
a Nonius KappaCCD or a Bruker-Nonius X8 Proteum diffractometer
with graded-multilayer focusing optics as described previously.59
Crystallographic data (excluding structure factors) for the struc-
tures in this paper have been deposited with the Cambridge Crys-
tallographic Data Centre as supplementary publication nos. CCDC
827884e827887. Copies of the data can be obtained, free of charge,
on application to CCDC, 12 Union Road, Cambridge CB2 1EZ, UK,
(DPDB) (40 mg, 0.1 mmol), and powdered K3PO4 (0.95 mg) in tol-
uene (3.5 mL) were heated at 100 ꢀC in a sealed tube under a ni-
trogen atmosphere as described previously.4 The tube was allowed
to cool to room temperature and the reaction mixture was passed
through a CeliteÒ bed. The residue was washed with dichloro-
methane (2ꢃ25 mL) and the combined filtrate was concentrated
under reduced pressure. The residue was purified by flash chro-
matography on silica gel with n-hexane as eluent and the pure
compound was crystallized from methanoledichloromethane to
yield 4,40,6-trichloro-2-methoxybiphenyl (6a) as a colorless solid in
18% yield. Mp: 58e59 ꢀC (chloroformemethanol); 1H NMR
(300 MHz, CDCl3):
system, 2H), 7.13 (d, J¼1.8 Hz, 1H), 6.87 (d, J¼1.8 Hz, 1H), 3.73 (s, 3H,
eOCH3); 13C NMR (100 MHz, CDCl3):
/ppm 158.1, 134.7, 134.3,
133.7, 132.8, 131.7, 128.3, 127.3, 121.6, 110.2, 56.2; Anal. Calcd for
C13H9Cl3O: C, 54.30; H, 3.15; found: C, 54.39; H, 3.13; mass spec-
trum m/z (relative abundance %): 286 (Mꢄþ, 100), 249 (6), 236 (82),
216 (20), 173 (40).
Acknowledgements
d
/ppm 7.41 (AAXX0 system, 2H), 7.20 (AA0XX0
This research was supported by grants ES05605, ES013661, and
ES017425 from the National Institute of Environmental Health
Sciences (NIEHS), National Institutes of Health (NIH). Contents of
this manuscript are solely the responsibility of the authors and do
not necessarily represent the official views of the NIEHS/NIH.
d
Supplementary data
4.3.2. 2,20,50,6-Tetrachloro-4-methoxybiphenyl 6b. Synthesized as
described above by the Suzuki coupling of 3c (0.50 g, 1.66 mmol)
and 2,5-dichlorophenylboronic acid (5b) (0.48 g, 2.5 mmol) to af-
ford 6b as a colorless solid in 77% yield. Mp: 87 ꢀC (chlor-
Supplementary data associated with this article can be found in
References and notes
oformemethanol); 1H NMR (400 MHz, CDCl3):
d
/ppm 7.41 (d,
J¼8.8 Hz, 1H), 7.32 (dd, J¼2.4 and 8.8 Hz, 1H), 7.21 (d, J¼2.4 Hz, 1H),
6.97 (s, 2H), 3.84 (s, 3H, eOCH3); 13C NMR (100 MHz, CDCl3):
/ppm
1. Naidu, A. B.; Ganapathy, D.; Sekar, G. Synthesis 2010, 3509.
2. Pacuszka, T.; Panasiewicz, M. J. Labelled Compd. Radiopharm. 2000, 43, 1255.
3. Waller, S. C.; He, Y. A.; Harlow, G. R.; He, Y. Q.; Mash, E. A.; Halpert, J. R. Chem.
Res. Toxicol. 1999, 12, 690.
d
159.9, 137.3, 135.2, 132.7, 132.4, 131.5, 130.5, 129.7, 128.2, 113.9, 55.8;
Anal. Calcd for C13H8Cl4O: C, 48.49; H, 2.48; found: C, 48.73; H, 2.37;
4. Joshi, S. N.; Vyas, S. M.; Duffel, M. W.; Parkin, S.; Lehmler, H. J. Synthesis 2011,
1045.
5. Comins, D. L.; Baevsky, M. F.; Hong, H. J. Am. Chem. Soc. 1992, 114, 10971.
6. Springer, D. M.; Luh, B.-Y.; Goodrich, J.; Bronson, J. J. Bioorg. Med. Chem. 2003, 11,
265.
þ
HRMS m/z: calculated for C13H8OCl4 (Mꢄ
) 319.9324, found
319.9325.
4.3.3. 4,40,6-Trichlorobiphenyl-2-ol 7a. BBr3 (1.2 mL, 1.2 mmol, 1 M
solution in heptane) was added to a stirred solution of 6a (70 mg,
0.24 mmol) in anhydrous CH2Cl2 (5 mL) under a nitrogen atmo-
sphere.3 The reaction was stirred at room temperature for 5 days,
quenched by pouring onto crushed ice and extracted with
dichloromethane (5 mL). The organic layer was washed with 2 M
NaOH solution (5 mL), the aqueous layer was acidified with 2 N HCl
(5 mL) and extracted with dichloromethane (3ꢃ5 mL). The com-
bined organic layer was washed with water (25 mL), brine (25 mL),
dried over (Na2SO4), and concentrated under reduced pressure. The
crude product was purified by column chromatography on silica gel
using a hexaneechloroform gradient (100%e90% hexane) to yield
4,40,6-trichlorobiphenyl-2-ol (7a) as a colorless oil in 29% yield. 1H
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11. Buchgraber, P.; Snaddon, T. N.; Wirtz, C.; Mynott, R.; Goddard, R.; Fuerstner, A.
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13. Tsuji, J. Transition Metal Reagents and Catalysts. Innovations in Organic Synthesis;
John Wiley: Chichester, UK, 2000.
14. Diederich, F.; Stang, P. J. Metal-Catalyzed Cross-Coupling Reactions; Wiley-VCH
GmbH: Weinheim, 1998.
15. Stavber, S.; Jereb, M.; Zupan, M. Synthesis 2008, 1487.
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19. Kung, P.-P.; Meng, J. J. International patent WO 2010018481, 2010.
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NMR (400 MHz, CDCl3):
d
/ppm 7.50 (AA0XX0 system, 2H), 7.26
(AA0XX0 system, 2H), 7.08 (d, J¼2.0 Hz, 1H), 6.93 (d, J¼2.0 Hz, 1H),
4.95 (s, 1H, eOH); 13C NMR (100 MHz, CDCl3):
d/ppm 154.2, 135.4,
134.7, 134.3, 131.9, 130.8, 129.8, 124.9, 121.9, 114.8; mass spectrum
m/z (relative abundance %): 272 (Mꢄþ, 47), 236 (18), 237 (38), 202
(100), 173 (42), 139 (46), 118 (27), 86 (82); HRMS m/z: calculated for
C12H6OCl3 [MꢁH] 270.9484, found 270.9481.
24. Di Fabio, R.; Giacobbe, S.; Bertani, B.; Micheli, F. World patent WO 9712870,
1997.
4.3.4. 2,20,50,6-Tetrachlorobiphenyl-4-ol 7b. Prepared from 2,20,50,6-
tetrachloro-4-methoxybiphenyl (6b) (0.31 g, 1 mmol) as described
above to afford 7b as a colorless solid in 87% yield. Mp: 101 ꢀC
25. Waring, W. S. Great Britain patent GB 895395, 1962.
26. Lee, D.; Marino, J. P.; Zhao, Y. World patent WO 2005009993, 2005.
27. Sugiyama, T. Bull. Chem. Soc. Jpn. 1981, 54, 2847.
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(chloroformemethanol); 1H NMR (400 MHz, CDCl3):
d/ppm 7.42 (d,
J¼8.4 Hz, 1H), 7.33 (dd, J¼2.4 and 8.4 Hz, 1H), 7.21 (d, J¼2.4 Hz, 1H),