LETTER
Three-Step Synthesis of (Thio)xanthene and Dibenzothiepine/Dibenzoxepine
Chem. 2009, 74, 3978.
421
closure conditions. Despite this modest selectivity, the
method provides a convenient synthesis of these fused
heterocycles, and the sulfur analogues could easily be sep-
arated and isolated by column chromatography. A future
prospect is to use the protocol for synthesis of substituted
derivatives from suitably functionalized aromatic precur-
sors.
(8) Okuma, K.; Nojima, A.; Nahoko, M.; Shioji, K. Org. Lett.
2009, 11, 169.
(9) Synthesis of 2-(2-Bromophenylsulfanyl)benzaldehyde
(5a): 2-Fluorobenzaldehyde (3; 2.0 g, 16 mmol), 2-bromo-
thiophenol (4a; 3.0 g, 16 mmol) and anhyd K2CO3 (3.29 g,
23.8 mmol) were dissolved in MeCN (10 mL) and stirred at
100 °C for 30 min under MW conditions. The crude reaction
mixture was evaporated onto Celite and purified using
column chromatography on silica gel (eluent: heptane →
30% EtOAc in heptane). The title compound was obtained as
a colorless solid (3.97 g, 84%); Rf 0.61 (EtOAc–heptane,
1:2); mp 49–50 °C. 1H NMR (600 MHz, CDCl3): d = 10.39
(s, 1 H), 7.95 (dd, J = 7.6, 1.7 Hz, 1 H), 7.66 (dd, J = 7.9, 1.3
Hz, 1 H), 7.48–7.51 (m, 1 H), 7.43 (m, 1 H), 7.24–7.28 (m,
1 H), 7.14–7.21 (m, 3 H). 13C NMR (151 MHz, CDCl3): d =
191.8, 138.8, 135.7, 134.6, 134.4, 133.6, 133.3, 131.8,
131.6, 129.3, 128.4, 127.5, 126.4. GC–MS: m/z = 392 [M+].
Anal. Calcd for C13H9BrOS: C, 53.26; H, 3.09. Found: C,
53.22; H, 3.05.
Acknowledgment
We gratefully thank Prof. Phil S. Baran (The Scripps Research
Institute) for fruitful discussions.
References and Notes
(1) Bøgesø, K. P.; Bang-Andersen, B. In Textbook of Drug
Design and Discovery, 4th ed.; Krogsgaard-Larsen, P.;
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Synthesis of 2-(2-Bromophenoxy)benzaldehyde (5b):
2-Fluorobenzaldehyde (3; 2.0 g, 16 mmol), 2-bromophenol
(4b; 2.8 g, 16 mmol), and anhyd K2CO3 (3.29 g, 23.8 mmol)
were dissolved in anhyd DMF (20 mL) and the mixture was
refluxed for 2 h. The mixture was then diluted with EtOAc
(30 mL) and brine (100 mL); the layers were separated and
the aqueous layer was extracted with EtOAc (3 × 30 mL).
The combined organic layers were washed with 2 M aq
NaOH (2 × 20 mL) and H2O (20 mL), dried with MgSO4,
filtered, concentrated in vacuo onto Celite, and purified
using column chromatography on silica gel (eluent: heptane
→ 30% EtOAc in heptane). Compound 5b was obtained as
a pale-yellow solid (3.19 g, 71%); Rf 0.60 (EtOAc–heptane,
1:2); mp 62–63 °C. 1H NMR (600 MHz, CDCl3): d = 10.60
(s, 1 H), 7.96 (dd, J = 7.8, 1.6 Hz, 1 H), 7.66–7.70 (m, 1 H),
7.50 (m, 1 H), 7.32–7.37 (m, 1 H), 7.19 (td, J = 7.7, 0.8 Hz,
1 H), 7.10 (m, 2 H), 6.74 (d, J = 8.4 Hz, 1 H). 13C NMR (151
MHz, CDCl3): d = 189.2, 159.4, 152.5, 135.7, 134.2, 129.0,
128.6, 126.3, 126.1, 123.3, 121.7, 116.9, 115.5. GC–MS:
m/z = 276 [M+]. Anal. Calcd for C13H9BrO2: C, 56.34; H,
3.27. Found: C, 56.39; H, 3.25.
Synthesis of 2-Bromophenyl-2-vinylphenylsulfane (6a):
Methyltriphenylphosphonium iodide (3.31 g, 8.19 mmol)
was dissolved in anhyd THF (50 mL) and the solution was
cooled to 0 °C under an argon atmosphere. t-BuOK (1.15 g,
10.2 mmol) was added by which the solution turned yellow
and after stirring for 10 min, compound 5a (2.00 g, 6.82
mmol) was added and the mixture was allowed to reach r.t.
and stirred for 1.5 h. The crude mixture was concentrated in
vacuo directly onto Celite and purified using column
chromatography on silica gel (eluent: heptane → 30%
EtOAc in heptane). Compound 6a was obtained as a yellow
solid (1.98 g, 100%); Rf 0.77 (EtOAc–heptane, 1:2); mp 58–
59 °C. 1H NMR (600 MHz, CDCl3): d = 7.69 (dd, J = 7.9, 1.2
Hz, 1 H), 7.53 (dd, J = 7.9, 1.3 Hz, 1 H), 7.48 (dd, J = 7.7,
1.3 Hz, 1 H), 7.42 (m, 1 H), 7.29 (td, J = 7.6, 1.4 Hz, 1 H),
7.18 (dd, J = 17.4, 11.0 Hz, 1 H), 7.07–7.10 (m, 1 H), 6.97
(td, J = 7.6, 1.5 Hz, 1 H), 6.63 (dd, J = 8.0, 1.5 Hz, 1 H), 5.73
(dd, J = 17.4, 0.9 Hz, 1 H), 5.29 (dd, J = 11.0, 0.9 Hz, 1 H).
13C NMR (151 MHz, CDCl3): d = 141.3, 138.9, 136.0, 134.4,
132.8, 130.3, 129.7, 128.9, 128.2, 127.7, 126.5, 126.4,
121.6, 116.7. GC–MS: m/z = 290 [M+]. Anal. Calcd for
C14H11BrS: C, 57.74; H, 3.81. Found: C, 53.72; H, 3.85.
Synthesis of 1-Bromo-2-(2-vinylphenoxy)benzene (6b):
Methyltriphenylphosphonium iodide (5.51 g, 13.6 mmol)
was dissolved in anhyd THF (50 mL) and the solution was
cooled to 0 °C under an argon atmosphere. t-BuOK (1.64 g,
14.6 mmol) was added by which the solution turned yellow
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