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A. Heynderickx et al.
PAPER
suspension was degassed again for 15 min. The mixture was re-
fluxed and stirred under a positive pressure of N2 for 3 d. The sol-
vents were evaporated near to dryness and the aqueous residue was
extracted with Et2O. The organic phase was dried (MgSO4) and fil-
tered on Celite. After evaporation of the solvent under vacuum, the
crude product was purified by chromatography on silica gel.
2-(2,6-Dimethoxyphenyl)-3-(2,6-dimethylphenyl)benzo[b]thio-
phene (12)
This compound was prepared as described above from 3-bromo-2-
(2,6-dimethoxy)phenylbenzo[b]thiophene (130 mg, 0.37 mmol),
2,6-dimethylphenylboronic acid (224 mg, 1.5 mmol),
Ba(OH)2 8H2O (586 mg, 1.8 mmol), DME (5 mL), H2O (2 mL) and
Pd(PPh3)4 (42 mg, 0.038 mmol). After 4 d at reflux and standard
workup, the crude product was purified by chromatography on sili-
ca gel (cyclohexane–toluene, 5:3 gradient as eluent) to afford 80 mg
(0.21 mmol, 58%) of product 12 as solid; mp 134 °C.
2,3-Bis(2,6-dimethylphenyl)benzo[b]thiophene (9)
From 2,6-dimethylphenylboronic acid (285 mg): The product was
isolated by chromatography (cyclohexane) and recrystallised from
cyclohexane; yield:177 mg (74%); crystals; mp 149–151 °C.
1H NMR (CDCl3): = 1.88 (s, 6 H, CH3), 2.08 (s, 6 H, CH3), 6.80–
1H NMR (CDCl3): = 1.93 (s, 6 H, CH3), 3.54 (s, 6 H, OCH3), 6.38
(d, 2 H, J = 8.4 Hz), 6.85–7.34 (m, 7 H), 7.79 (d, 1 H, J = 8.0 Hz).
7.31 (m, 9 H), 7.80 (d, 1 H, J = 7.3 Hz).
13C NMR (CDCl3): = 19.99, 55.29, 103.62, 111.34, 122.06,
123.10, 123.53, 123.73, 124.54, 126.90, 130.05, 132.49, 134.48,
134.98, 138.25, 139.76, 140.30.
13C NMR (CDCl3): = 21.13, 21.51, 121.99, 123.68, 123.96,
124.19, 127.41, 127.75, 128.21, 132.68, 133.69, 134.13, 137.81,
138.23, 139.47, 140.29
MS: m/z = 374 (M+).
MS: m/z = 342 (M+).
Anal. Calcd for C24H22O2S (374.50): C, 76.97; H, 5.92; Found: C,
77.02; H, 6.10.
Anal. Calcd for C24H22S (342.5): C, 84.16; H, 6.47. Found: C,
84.14; H, 6.46.
References
2,3-Bis(2,6-dimethoxyphenyl)benzo[b]thiophene 10
From 2,6-dimethoxyphenylboronic acid (330 mg). The product was
isolated by chromatography (cyclohexane–CH2Cl2 5:3 gradient as
eluent) and recrystallised from cyclohexane; yield: 185 mg (65%);
crystals; mp 220 °C.
(1) (a) Benati, L.; Montevecchi, P. C. J. Chem. Soc., Perkin
Trans. 1 1992, 1659. (b) Benati, L.; Montevecchi, P. C.;
Spagnolo, P. J. Chem. Soc., Perkin Trans. 1 1991, 2103.
(c) Effenberger, F.; Russ, W. Chem. Ber. 1982, 115, 3719.
(d) Buquet, A.; Couture, A.; Lablache-Combier, A.; Pollet,
A. Tetrahedron 1981, 37, 75. (e) Marcuzzi, F.; Melloni, G.
Synthesis 1976, 451. (f) Sonoda, T.; Kawakami, M.; Ikeda,
T.; Kobayashi, S. J. Chem. Soc., Chem. Commun. 1976,
612. (g) Dann, O.; Fick, H.; Pieztner, B.; Walkenhorst, E.;
Fernbach, R.; Zeh, D. Liebigs Ann. Chem. 1975, 160.
(h) Modena, G.; Tonellato, U. J. Chem. Soc. (B) 1971, 381.
(i) Crenshaw, R. R.; Jeffries, A. T.; Luke, G. M.; Cheney, L.
C.; Bialy, G. J. Med. Chem. 1971, 14, 1185. (j) Sauter, F.;
Dzerovicz, A. Monatsch. Chem. 1970, 101, 1806.
1H NMR (CDCl3): = 3.51 (s, 6 H, OCH3), 3.58 (s, 6 H, OCH3),
6.48 (m, 4 H), 7.12–7.27 (m, 4 H), 7.37 (m, 1 H), 7.81 (m, 1 H).
13C NMR (CDCl3): = 55.34, 55.57, 103.59, 103.66, 112.79,
113.52, 121.88, 122.99, 123.23, 123.66, 128.55, 128.66, 129.32,
133.25, 139.57, 140.08, 158.47.
MS: m/z = 406 (M+).
Anal. Calcd for C24H22O4S (406.5): C, 71.91; H, 5.46. Found: C,
71.88; H, 5.42.
(k) Capozzi, G.; Melloni, G.; Modena, G. J. Chem Soc.(C)
1970, 2621.
2-(2,6-Dimethylphenyl)-3-(2,6-dimethoxyphenyl)benzo[b]thio-
phene (11)
(2) Suzuki, A. J. Organomet. Chem. 1999, 576, 147.
(3) Sall, D.; Zhang, M. J. Med. Chem. 2000, 43, 649.
(4) (a) Bussolari, J.; Rehborn, D. Organic Lett. 1999, 1, 965.
(b) Pinto, D.; Copeland, R.; Covington, M.; Pitts, W.; Batt,
D.; Orwat, M.; Lam, G.; Joshi, A.; Chan, Y.; Wang, S.;
Trzaskos, J.; Magolda, R.; Kornhauser, D. Bioorg. Med.
Chem. Lett. 1996, 6, 2907.
(5) Miyaura, N.; Ishiyama, T.; Sasaki, H.; Ishikawa, M.; Satoh,
M.; Suzuki, A. J. Am. Chem. Soc. 1989, 111, 314.
(6) Sura, T.; MacDowel, D. J. Org. Chem. 1993, 58, 4360.
(7) Vallgarda, J.; Apppelberg, U.; Arvidsson, L. E.; Hjorth, S.;
Svensson, B.; Hacksell, U. J. Med. Chem. 1996, 39, 1485.
(8) Dalmann, U.; Neidlein, R. Helv. Chim. Acta 1997, 80, 111.
(9) The assignment of the signals was realised by comparison
with analogous compounds: Viswanatha, V.; Hruby, V. J.
Org. Chem. 1979, 44, 2892.
A mixture of 3 (590 mg, 1.86 mmol), 2,6-dimethoxyphenylboronic
acid (676 mg, 3.71 mmol), Ba(OH)2 8H2O (1.46 g, 4.65 mmol),
DME (10 mL) and H2O (4 mL) was degassed and flushed with N2
for 60 min. Then, the catalyst Pd(PPh3)4 (107 mg, 0.093 mmol) was
quickly added and the resulting suspension was degassed again for
15 min. The mixture was refluxed under a positive pressure of N2
for 3 d. The solvents were evaporated near to dryness and the aque-
ous residue was extracted with Et2O. The organic phase was dried
(MgSO4) and filtered on Celite. After evaporation of the solvent un-
der vacuum, the crude product was purified by chromatography on
silica gel (cyclohexane–toluene, 5:3 gradient as eluent) to afford
494 mg (71%) of product 11 as solid; mp 139 °C.
1H NMR (CDCl3): = 2.11 (s, 6 H, CH3), 3.47 (s, 6 H, OCH3), 6.42
(d, 2 H, J = 8.4 Hz), 6.87–7.28 (m, 7 H), 7.78 (m, 1 H).
13C NMR (CDCl3): = 20.32, 54.99, 103.54, 111.97, 121.83,
123.48, 123.58, 126, 88, 127.65, 127.93, 129.21, 133.31, 138.64,
139.34, 139.41, 140.54, 158.58
(10) (a) Miyaura, N.; Suzuki, A. Chem. Rev. 1995, 95, 2457.
(b) Suzuki, A. Pure Appl. Chem. 1994, 66, 213.
MS: m/z = 374 (M+).
(c) Watanabe, T.; Miyaura, N.; Suzuki, A. Synlett 1992, 207.
(11) Coulson, D. R. Inorg. Synth. 1972, 13, 121.
Anal. Calcd for C24H22O2S (374.50): C, 76.97; H, 5.92. Found: C,
76.88; H, 6.01.
Synthesis 2002, No. 2, 213–216 ISSN 0039-7881 © Thieme Stuttgart · New York