Synthesis of dibenzothiophene, dibenzofuran and carbazole donor-acceptor chromophores

Article abstract of DOI:10.1055/s-0032-1318484

We present efficient synthetic protocols for functionalizing dibenzothiophene, dibenzofuran, and carbazole with hydroxy and nitro or cyano groups. The synthesis of these donor-acceptor chromophores is based on a key Suzuki-Miyaura coupling using an approp

Full text of DOI:10.1055/s-0032-1318484

PAPER
▌1115
paper
Synthesis of Dibenzothiophene, Dibenzofuran and Carbazole Donor–Acceptor
Chromophores
Dibenzo-Fused Donor–Acceptor Heterocycles
Tue Heesgaard Jepsen,a,b Mogens Larsen,b Morten Jørgensen,b Mogens Brøndsted Nielsen*a
a
Department of Chemistry, University of Copenhagen, Universitetsparken 5, 2100 Copenhagen Ø, Denmark
Fax +4535320212; E-mail: mbn@kiku.dk
b
Medicinal Chemistry Research, H. Lundbeck A/S, Ottiliavej 9, 2500 Valby, Denmark
Received: 04.02.2013; Accepted after revision: 27.02.2013
Abstract: We present efficient synthetic protocols for functionaliz-
ing dibenzothiophene, dibenzofuran, and carbazole with hydroxy
and nitro or cyano groups. The synthesis of these donor–acceptor
chromophores is based on a key Suzuki–Miyaura coupling using an
appropriately substituted aromatic boronic acid. Subsequent intra-
molecular SNAr reaction allows formation of the dibenzothiophene
and dibenzofuran scaffolds, while a carbon–hydrogen activation re-
action is employed to afford the carbazole. A final demethylation
step unmasks the phenol moiety of the tricyclic chromophores. The
UV/Vis absorption properties of the phenol and phenolate forms of
these chromophores are also studied.
O2N
O2N
O2N
OH
OH
OH
S
1
O
2
Key words: dibenzothiophene, dibenzofuran, carbazole, hetero-
cycles, palladium, phenols
N
H
3
Figure 1 Tricyclic heterocyclic donor–acceptor chromophores 1–3
Nitrophenolates are key examples of donor–acceptor
chromophores, which are interesting in terms of their lin-
ear and nonlinear optical properties.1 Considerable effort
has been focused on functionalizing oligo(phenylene)s,
oligo(phenylene-ethynylene)s, and oligo(phenylenevinyl-
ene)s with hydroxy and nitro substituents.1 Along these
lines, we became interested in developing synthetic proto-
cols for preparing related donor–acceptor chromophores
based on conformationally-locked heterocyclic scaffolds:
dibenzothiophene, dibenzofuran and carbazole. Three
such target molecules (1–3) are shown in Figure 1. Syn-
thetically, we took advantage of our previously reported
three-step protocol for the synthesis of functionalized
dibenzothiophenes based on palladium-catalyzed carbon–
carbon (C–C) and carbon–sulfur (C–S) bond formation,2
and related methods for preparing dibenzofurans3 and car-
bazoles.4,5
yield. In order to obtain the desired nitrophenol 1, the final
step was demethylation of the methoxy group. Numerous
experiments with various reagents under different condi-
tions were examined, but the transformation was surpris-
ingly challenging due to the very poor solubility of 4.
Initial attempts using boron tribromide (BBr3) and boron
trichloride (BCl3) in the presence of tetrabutylammonium
iodide (TBAI), at temperatures ranging from –78 to 60 °C
and in different solvents (CH2Cl2, CHCl3, MeCN), as well
as heating at reflux temperature in concentrated aqueous
hydrobromic acid or concentrated hydrogen bromide in
acetic acid, all failed. Reactions with excess lithium io-
dide (LiI) in N,N-dimethylformamide at reflux tempera-
ture also resulted in no conversion of 4, whereas treatment
with trimethylsilyl iodide (TMSI) fully, or partly, reduced
the nitro group into the corresponding amino and nitroso
compounds. Gratifyingly, heating in neat pyridine hydro-
chloride (py·HCl) at 200 °C for 10 minutes in a micro-
wave (MW) oven led to full conversion of 4, and the
desired nitrophenol 1 was obtained in 92% yield. Al-
though the temperature seems relatively high, it can be
reached rapidly by the use of microwave heating, and the
short reaction time prevented any formation of by-prod-
ucts. Thus, an efficient protocol for preparing target mol-
ecule 1 was developed with an overall yield of 54% being
obtained over the four steps.
The synthesis of 7-nitrodibenzo[b,d]thiophen-3-ol (1)
started with preparation of the corresponding methoxy de-
rivative 4 via our three-step protocol (Scheme 1).2 A
Suzuki–Miyaura coupling6 between aryl dibromide 5 and
boronic acid 6 furnished biphenyl compound 7 in 81%
yield, and a subsequent palladium-catalyzed carbon–
sulfur coupling with ethyl 3-mercaptopropanoate7 gave
sulfide 8 in 82% yield. Next, the thiolate was generated by
elimination under basic conditions, which underwent an
in situ intramolecular nucleophilic aromatic substitution
(SNAr) reaction to afford dibenzothiophene 4 in 89%
SYNTHESIS 2013, 45, 1115–1120
Advanced online publication: 14.03.2013
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X
DOI: 10.1055/s-0032-1318484; Art ID: SS-2013-T0102-OP
© Georg Thieme Verlag Stuttgart · New York

1116
T. H. Jepsen et al.
PAPER
F
MeO
OMe
O2N
MeO
OMe
F
(HO)2B
OMe
O2N
(HO)2B
Br
F
Br
py⋅HCl
6
12
OMe
PdCl2(PPh3)2
K2CO3
DME, H2O
80 °C, 4 h
93%
200 °C
MW, 10 min
91%
[PdCl2(PPh3)2]
O2N
O2N
Br
K2CO3
F
11
DME, H2O
80 °C, 5 h
5
Br
13
7
81%
F
O
HO
OH
HS
OEt
OMe KOt-Bu
O2N
Pd2(dba)3, dpephos
K2CO3, toluene
110 °C, 16 h
THF, 150 °C
MW, 30 min
89%
Cs2CO3
S
OH
O2N
MeCN
150 °C
MW, 30 min
78%
8
O
O
82%
O2N
F
2
OEt
14
Scheme 3 Synthesis of 7-nitrodibenzo[b,d]furan-3-ol (2)
py⋅HCl
OMe
OH
O2N
O2N
200 °C
MW, 10 min
92%
S
S
4
1
phenyl 18 in 86% yield. The palladium-catalyzed carbon–
hydrogen activation was performed according to
Buchwald’s procedure4a under an oxygen atmosphere in
the presence of a stoichiometric amount of copper(II) ac-
etate. In the event, carbazole 19 was obtained in 92%
yield. Subsequent demethylation and deacetylation were
completed efficiently by heating at reflux temperature in
concentrated aqueous HBr to afford the desired phenol 3
in 79% yield; an overall yield of 58% of 3 was obtained
over the four steps.
Scheme 1 Synthesis of 7-nitrodibenzo[b,d]thiophen-3-ol (1)
The cyano group represents an alternative acceptor group,
and by subjecting previously prepared 7-methoxydiben-
zo[b,d]thiophene-3-carbonitrile (9)2 to the pyridine hy-
drochloride demethylation conditions, phenol 10 was
obtained in an isolated yield of 90% (Scheme 2).
py⋅HCl
OMe
OH
NC
NC
200 °C
MW, 10 min
90%
OMe
S
S
9
10
Br
Br
(HO)2B
Ac2O
17
Scheme 2 Synthesis of 3-hydroxy-7-cyanodibenzothiophene (10)
CH2Cl2
r.t., 24 h
92%
O2N
NH2
PdCl2(PPh3)2
O2N
NHAc
K2CO3
DME, H2O
80 °C, 5 h
86%
15
16
The synthesis of the dibenzofuran derivative 2 was in-
spired by the work of Liu et al.3 Initially, commercially
available bromide 11 and boronic acid 12 were coupled
via a Suzuki–Miyaura reaction to afford the correspond-
ing biphenyl 13 in 93% yield (Scheme 3). The subsequent
demethylation was achieved as described above to give
the desired bis-phenol 14 in 91% isolated yield. On react-
ing 14 with cesium carbonate at 150 °C in acetonitrile for
30 minutes under microwave irradiation, the desired
dibenzofuran 2 was obtained through an intramolecular
ring-closure, in a yield of 78% (Scheme 3). The synthesis
of this target molecule proceeded in an overall yield of
66% over three steps. Attempts to perform the ring-clo-
sure with sodium tert-butoxide as the base in tetrahydro-
OMe
OMe
Pd(OAc)2 (5 mol%)
Cu(OAc)2 (1 equiv)
N
O2N
O2, toluene
120 °C, 2 d
92%
Ac
O2N
NHAc
18
19
OH
concd aq HBr
N
H
reflux, 1 h
79%
O2N
3
furan resulted in the formation of several by-products, Scheme 4 Synthesis of 7-nitro-9H-carbazol-2-ol (3)
most likely involving redox reactions of the nitro group.
The UV/Vis absorption properties of the new chromo-
phores 1–3 and 10, and their corresponding phenolates
were measured in methanol as the solvent. Sodium
methoxide was used as the base to form the phenolate an-
ions (Figure 2, Table 1). As expected, the longest-wave-
length absorption maxima of all the phenolate anions were
clearly red-shifted compared to the neutral phenol species,
by approximately 0.5 eV.
Our synthesis of the carbazole derivative 3 was inspired
by the work of Buchwald and colleagues,4 since the key
step of our strategy was an intramolecular ring-closure to
give the carbazole scaffold based on oxidative carbon–
hydrogen (C–H) activation. Scheme 4 summarizes the
protocol starting with acetylation of the commercially
available aniline 15, followed by a Suzuki–Miyaura cou-
pling of the product 168 with boronic acid 17 to afford bi-
Synthesis 2013, 45, 1115–1120
© Georg Thieme Verlag Stuttgart · New York

PAPER
Dibenzo-Fused Donor–Acceptor Heterocycles
1117
rivative. The blue-shifted absorption of the phenolate of
10 relative to that of the phenolate of 1 can be explained
by the weaker acceptor strength of the cyano group, which
should result in a lowest unoccupied molecular orbital
(LUMO) of higher energy in 10.
Table 1 Longest-Wavelength Absorption Maxima (λmax/nm) in
Methanol
Compound
Phenol
Phenolatea
ΔE (eV)b
1
355
356
373
312
421
421
443
353
0.55
0.54
0.53
0.46
2
3
10
a Generated by addition of NaOMe.
b Energy difference between the phenolate and phenol absorptions.
In conclusion, we have synthesized four new tricyclic het-
erocyclic donor–acceptor chromophores containing a hy-
droxy donor end and a nitro or cyano acceptor end, by
very efficient strategies. Each procedure relied on a key
Suzuki–Miyaura coupling, using an appropriately substi-
tuted aromatic boronic acid and different bromide deriva-
tives. Intramolecular SNAr reactions gave rise to the
dibenzothiophene and dibenzofuran scaffolds, while a
carbon–hydrogen activation step was employed for the
preparation of the carbazole scaffold. Finally, the reaction
conditions were optimized for the demethylation step,
which unmasks the phenol unit of these tricyclic chromo-
phores. The UV/Vis absorption properties of the phenol
and phenolate forms of the chromophores were studied,
which will be followed by more advanced measurements.
Chemicals were purchased from Aldrich, Acros, Merck or Fluka
and were used without further purification. Microwave (MW) ex-
periments were performed using a Biotage Advancer Microwave
Synthesizer using standard MW vials. All reactions were monitored
by GC–MS and TLC (Merck 5554). Column chromatography was
accomplished using Merck silica gel (40–63 μm) as the stationary
phase. Melting points were determined on a Büchi apparatus and are
uncorrected. IR spectra were obtained on a Perkin-Elmer Spectrum
One IR spectrophotometer with a universal ATR accessory and the
signals are reported in wavenumbers (cm–1). Solid samples were ei-
ther loaded directly or dissolved in CH2Cl2 and loaded, then allow-
ing the solvent to evaporate before recording the spectrum. NMR
spectra were recorded on either a 500 MHz Bruker Spectrospin in-
strument or a 600 MHz Bruker Ultrashield 600 Plus instrument;
deuterated solvents from Cambridge Isotope Labs and Aldrich were
Figure 2 UV/Vis absorption spectra of the neutral and anionic chro-
mophores
The absorption spectra of the nitrophenolates of 1 and 2 used. Proton and carbon chemical shifts are reported in parts per
million relative to solvent chemical shifts. GC–MS data were ob-
tained using a Varian gas chromatograph equipped with an EI mass
spectrometer as the detector and a Varian FactorFour VF-5ms silica
capillary column (10 m × 0.15 mm × 0.15 μm). UV/Vis absorption
showed similar absorption maxima (λmax = 421 nm) with
comparable molar absorptivities. The absorption of the
phenolate of the carbazole derivative 3 was somewhat
red-shifted (λmax ≈ 443 nm). It was apparent that oxygen
spectra were recorded on a Cary 50 Bio spectrophotometer. Ele-
and sulfur heteroatoms had little impact on the overall po-
sition of the charge-transfer absorption, while the pres-
ence of a nitrogen resulted in a significant change, most
likely being due to an increase in the energy of the highest
occupied molecular orbital (HOMO) of the carbazole de-
mental analyses were performed using a Flash EA 1112 fra Thermo
analyzer at the Department of Chemistry, University of Copenhagen.
2-Bromo-2′-fluoro-4′-methoxy-4-nitro-1,1′-biphenyl (7)
H2O (5 mL) and DME (40 mL) were added to a round-bottomed
flask, fitted with a condenser and Ar flow, and degassed with Ar.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1115–1120

1118
T. H. Jepsen et al.
PAPER
K2CO3 (3.08 g, 22.2 mmol), 1,2-dibromo-4-nitrobenzene (5) (2.50
g, 8.90 mmol), 2-fluoro-4-methoxyphenylboronic acid (6) (1.51 g,
8.90 mmol) and bis(triphenylphosphine)palladium(II) chloride
[PdCl2(PPh3)2] (625 mg, 0.890 mmol) were added to the mixture,
which was then heated at 80 °C for 5 h. The mixture was allowed to
cool to r.t., the DME was evaporated, and H2O (50 mL) and Et2O
(30 mL) were added. The layers were separated and the aq layer was
extracted with Et2O (3 × 30 mL). The combined organic layers were
washed with brine (ca. 20 mL), dried over MgSO4, filtered, and con-
centrated in vacuo to afford a yellow oil, which was purified by col-
umn chromatography on silica gel (heptane → 30% EtOAc in
heptane). The title compound was isolated as a colorless solid (2.34
g, 81%).
which were recrystallized from MeCN to afford the pure compound
as pale brown needle-shaped crystals (194 mg, 89%).
Mp 227–228 °C; Rf = 0.40 (EtOAc–heptane, 1:5).
1H NMR (600 MHz, CDCl3): δ = 8.71 (d, J = 2.1 Hz, 1 H), 8.29 (dd,
J = 8.7, 2.1 Hz, 1 H), 8.10 (m, 2 H), 7.36 (d, J = 2.3 Hz, 1 H), 7.13
(dd, J = 8.8, 2.3 Hz, 1 H), 3.94 (s, 3 H).
13C NMR (151 MHz, CDCl3): δ = 160.6, 145.3, 143.7, 140.5, 138.7,
127.3, 123.7, 120.6, 119.9, 118.8, 114.8, 105.7.
GC–MS: tR = 4.467 min, m/z = 259 [M+].
Anal Calcd for C13H9NO3S: C, 60.22; H, 3.50; N, 5.40. Found:
60.16; H, 3.56; N, 5.45.
Mp 62–63 °C; Rf = 0.75 (EtOAc–heptane, 1:2).
7-Nitrodibenzo[b,d]thiophen-3-ol (1)
1H NMR (600 MHz, CDCl3): δ = 8.55 (d, J = 2.3 Hz, 1 H), 8.21 (dd,
J = 8.4, 2.3 Hz, 1 H), 7.49 (d, J = 8.4 Hz, 1 H), 7.21 (t, J = 8.5 Hz,
1 H), 6.81 (dd, J = 8.5, 2.5 Hz, 1 H), 6.74 (m, 1 H), 3.87 (s, 3 H).
13C NMR (151 MHz, CDCl3): δ = 161.7, 159.7 (d, J = 248.3 Hz),
147.5, 143.7, 132.4, 131.3, 128.0, 124.7, 122.1, 119.0, 110.1, 101.9
(d, J = 25.3 Hz), 55.6.
Compound 4 (100 mg, 0.386 mmol) was mixed with py·HCl (3.0 g,
26 mmol) under an Ar atm and heated in a vial for 10 min at 200 °C
under MW irradiation conditions. After full conversion of 4, the sol-
id reaction mass was dissolved in sat. aq NH4Cl soln (100 mL) and
extracted with EtOAc (3 × 20 mL). The combined organics were
washed with brine (20 mL), dried over MgSO4, filtered, concentrat-
ed onto Celite and purified by column chromatography on silica gel
(heptane → 50% EtOAc in heptane). The title compound was re-
crystallized from MeCN and isolated as a colorless solid (87 mg,
92%).
GC–MS: tR = 3.127 min; m/z = 325 [79Br, M+].
Anal Calcd for C13H9BrFNO3: C, 47.88; H, 2.78; N, 4.29. Found:
47.79; H, 2.77; N, 4.35.
Mp 248–249 °C; Rf = 0.33 (EtOAc–heptane, 1:2).
Ethyl 3-{(2′-Fluoro-4′-methoxy-4-nitro-[1,1′-biphenyl]-2-
yl)sulfanyl}propanoate (8)
IR (ATR): 3401, 1634, 1514, 1444, 1368, 1336, 1296, 1217, 1144,
1115, 1064, 952, 864, 852, 809, 757, 736, 640 cm–1.
1H NMR (600 MHz, DMSO-d6): δ = 10.32 (s, 1 H), 8.98 (d, J = 2.2
Hz, 1 H), 8.39 (d, J = 8.7 Hz, 1 H), 8.32 (d, J = 8.7 Hz, 1 H), 8.27
(dd, J = 8.7, 2.2 Hz, 1 H), 7.43 (d, J = 2.2 Hz, 1 H), 7.05 (dd,
J = 8.7, 2.2 Hz, 1 H).
13C NMR (151 MHz, DMSO-d6): δ = 158.7, 144.5, 143.4, 140.5,
137.9, 125.5, 124.6, 121.0, 119.8, 119.2, 115.1, 108.2.
GC–MS: tR = 4.231 min, m/z = 245 [M+].
UV/Vis (MeOH): λmax = 355 nm (ε = 16 × 103 M–1·cm–1).
A Schlenk tube was dried with a heat gun and cooled under an Ar
atm. Anhyd toluene (20 mL) was added to the tube and degassed
with Ar. Compound 7 (1.15 g, 3.53 mmol), ethyl 3-mercaptopro-
panoate (0.520 g, 3.88 mmol), Pd2(dba)3 (161 mg, 0.176 mmol),
bis(2-diphenylphosphinophenyl)ether (dpephos) (191 mg, 0.351
mmol) and oven-dried K2CO3 (1.22 g, 8.83 mmol) were added. The
mixture was then degassed with Ar, the Schlenk tube sealed and the
contents stirred at 110 °C for 16 h. The mixture was quenched with
5% aq citric acid soln (20 mL) and diluted with EtOAc (20 mL). The
two layers were separated, and the aq layer was extracted with
EtOAc (3 × 20 mL). The combined organic layers were washed
with brine (ca. 20 mL), dried over MgSO4, filtered, and evaporated
in vacuo to give a brown oil, which was purified by column chro-
matography on silica gel (heptane → 30% EtOAc in heptane). The
title compound was isolated as a pale yellow oil (1.10 g, 82%).
Anal Calcd for C12H7NO3S: C, 58.77; H, 2.88; N, 5.71. Found:
58.72; H, 2.96; N, 5.75.
7-Hydroxydibenzo[b,d]thiophene-3-carbonitrile (10)
An identical procedure to that used for preparing compound 1 was
followed by reacting substrate 9 (20 mg, 0.08 mmol) and py·HCl
(480 mg, 4.2 mmol) at 200 °C for 10 min under MW irradiation
conditions. The title compound was isolated as a colorless solid (17
mg, 90%).
Rf = 0.72 (EtOAc–heptane, 1:2).
1H NMR (600 MHz, CDCl3): δ = 8.22 (d, J = 2.3 Hz, 1 H), 8.06 (dd,
J = 8.3, 2.3 Hz, 1 H), 7.38 (d, J = 8.3 Hz, 1 H), 7.19 (t, J = 8.5 Hz,
1 H), 6.81 (m, 1 H), 6.73 (m, 1 H), 4.14 (q, J = 7.1 Hz, 2 H), 3.86
(s, 3 H), 3.18 (t, J = 7.4 Hz, 2 H), 2.61 (t, J = 7.4 Hz, 2 H), 1.25 (t,
J = 7.1 Hz, 3 H).
13C NMR (151 MHz, CDCl3): δ = 171.2, 161.6, 159.8 (d, J = 247.7
Hz), 147.8, 142.2, 139.3, 131.8, 131.3, 121.8, 120.3, 118.0 (d,
J = 16.1 Hz), 110.1, 101.8 (d, J = 25.5 Hz), 60.8, 55.7, 33.6, 28.1,
14.0.
Mp 250–251 °C; Rf = 0.54 (EtOAc–heptane, 1:1).
IR (ATR): 3352, 2231, 1615, 1562, 1461, 1428, 1335, 1284, 1203,
905, 878, 805, 703, 624 cm–1.
1H NMR (600 MHz, DMSO-d6): δ = 10.25 (s, 1 H), 8.53 (s, 1 H),
8.35 (d, J = 8.2 Hz, 1 H), 8.28 (d, J = 8.6 Hz, 1 H), 7.84 (d, J = 8.2
Hz, 1 H), 7.40 (d, J = 2.2 Hz, 1 H), 7.03 (dd, J = 8.6, 2.2 Hz, 1 H).
13C NMR (151 MHz, DMSO-d6): δ = 158.4, 142.1, 138.9, 137.8,
127.8, 127.2, 125.9, 124.2, 121.4, 119.1, 114.8, 108.1, 107.0.
GC–MS: tR = 6.795 min, m/z = 379 [M+].
Anal Calcd for C18H18FNO5S: C, 56.98; H, 4.78; N, 3.69. Found:
56.99; H, 4.86; N, 3.61.
GC–MS: tR = 3.257 min, m/z = 225 [M+].
UV/Vis (MeOH): λmax = 312 nm (ε = 28 × 103 M–1·cm–1).
3-Methoxy-7-nitrodibenzo[b,d]thiophene (4)
A MW vial was purged with Ar and anhyd THF (5 mL) was added.
Compound 8 (0.72 g, 1.9 mmol) and KOt-Bu (319 mg, 2.85 mmol)
were added to the vial and the resulting mixture stirred at 150 °C for
30 min under MW irradiation. The mixture was quenched with 5%
aq citric acid soln (20 mL) and diluted with EtOAc (10 mL). The
two layers were separated, and the aq layer was extracted with
EtOAc (3 × 20 mL). The combined organic layers were washed
with brine (ca. 20 mL), dried over MgSO4, filtered, and evaporated
in vacuo. The title compound was obtained as dark brown crystals,
Anal Calcd for C13H7NOS: C, 69.31; H, 3.13; N, 6.22. Found: C,
69.23; H, 3.20; N, 6.15.
2-Fluoro-2′,4′-dimethoxy-4-nitro-1,1′-biphenyl (13)
The procedure for preparing compound 7 was followed using
K2CO3 (3.80 g, 27.5 mmol), 1-bromo-2-fluoro-4-nitro-benzene (11)
(2.42 g, 11.0 mmol), 2,4-dimethoxyphenylboronic acid (12) (2.00 g,
11.0 mmol), and PdCl2(PPh3)2 (386 mg, 0.550 mmol) in DME (40
mL) and H2O (5 mL). The product was purified by column chroma-
Synthesis 2013, 45, 1115–1120
© Georg Thieme Verlag Stuttgart · New York

PAPER
Dibenzo-Fused Donor–Acceptor Heterocycles
1119
tography on silica gel (heptane → 30% EtOAc in heptane). The title
compound was isolated as a yellow solid by recrystallization from
MeCN (2.82 g, 93%).
1H NMR (600 MHz, CDCl3): δ = 9.28 (s, 1 H), 7.84 (dd, J = 8.8, 2.7
Hz, 1 H), 7.73 (m, 2 H), 2.30 (s, 3 H).
13C NMR (151 MHz, CDCl3): δ = 168.3, 147.8, 136.7, 132.8,
Mp 106–107 °C; Rf = 0.16 (EtOAc–heptane, 1:5).
119.34, 119.31, 116.3, 24.9.
1H NMR (600 MHz, CDCl3): δ = 8.06 (dd, J = 8.4, 2.3 Hz, 1 H),
7.98 (dd, J = 9.5, 2.3 Hz, 1 H), 7.53 (dd, J = 8.4, 7.3 Hz, 1 H), 7.20
(dd, J = 8.3, 0.5 Hz, 1 H), 6.62–6.57 (m, 2 H), 3.88 (s, 3 H), 3.80 (s,
3 H).
13C NMR (151 MHz, CDCl3): δ = 161.9, 159.5 (d, J = 251.9 Hz),
157.8, 147.4, 133.5 (d, J = 16.0 Hz), 132.6, 131.6, 118.8, 115.3,
111.4 (d, J = 28.2 Hz), 104.8, 98.9, 55.5.
GC–MS: tR = 3.254 min, m/z = 258 [79Br, M+].
N-(4′-Methoxy-4-nitro-[1,1′-biphenyl]-2-yl)acetamide (18)
The procedure for preparing compound 7 was followed using
K2CO3 (5.23 g, 37.8 mmol), acetamide 16 (4.0 g, 15.0 mmol),
4-methoxyphenylboronic acid (17) (2.58 g, 17.0 mmol) and
PdCl2(PPh3)2 (530 mg, 0.756 mmol) in DME (50 mL) and H2O (10
mL). The title compound was isolated as a yellow powder (3.8 g,
86%).
GC–MS: tR = 3.965 min, m/z = 277 [M+].
Mp 151 °C; Rf = 0.34 (EtOAc–heptane, 1:1).
Anal Calcd for C14H12FNO4: C, 60.65; H, 4.36; N, 5.05. Found: C,
60.63; H, 4.32; N, 5.10.
1H NMR (600 MHz, CDCl3): δ = 9.23 (s, 1 H), 8.00 (dd, J = 8.2, 1.9
Hz, 1 H), 7.36 (d, J = 8.3 Hz, 1 H), 7.33–7.27 (m, 3 H), 7.07 (d,
J = 8.2 Hz, 2 H), 3.90 (s, 3 H), 2.09 (s, 3 H).
13C NMR (151 MHz, CDCl3): δ = 168.3, 160.2, 147.5, 137.4, 135.8,
130.7, 130.1, 128.0, 118.8, 116.1, 115.0, 55.4, 24.7.
2′-Fluoro-4′-nitro-[1,1′-biphenyl]-2,4-diol (14)
The procedure for preparing compound 1 was followed by reacting
compound 13 (1.14 g, 4.11 mmol) and py·HCl (12.0 g, 104 mmol)
at 200 °C for 10 min under MW irradiation conditions. The title
compound was isolated as a yellow oil (0.93 g, 91%).
GC–MS: tR = 3.367 min, m/z = 286 [M+].
Rf = 0.31 (EtOAc–heptane, 1:2).
Anal Calcd for C15H14N2O4: C, 62.93; H, 4.93; N, 9.79. Found: C,
62.90; H, 4.96; N, 9.88.
1H NMR (600 MHz, DMSO-d6): δ = 9.83 (s, 1 H), 9.72 (s, 1 H),
8.09–8.03 (m, 2 H), 7.63 (t, J = 8.3 Hz, 1 H), 7.03 (d, J = 8.3 Hz, 1
H), 6.46 (d, J = 2.1 Hz, 1 H), 6.36 (dd, J = 8.3, 2.1 Hz, 1 H).
1-(2-Methoxy-7-nitro-9H-carbazol-9-yl)ethanone (19)
A Schlenk tube was dried and cooled under an Ar atm. Compound
18 (1.0 g, 3.5 mmol), Pd(OAc)2 (39.2 mg, 0.175 mmol), and pow-
dered activated 3 Å MS (750 mg) were added. The flask was evac-
uated under vacuum and then filled with argon. Cu(OAc)2 (634 mg,
3.49 mmol) followed by anhyd toluene (15 mL) were added under
Ar. The mixture was degassed and refilled with O2 gas from a bal-
loon (3 times). The contents of the sealed tube were stirred at
120 °C for 2 d, during which precipitation was observed. The tolu-
ene was evaporated and CH2Cl2 (50 mL) and 5% aq citric acid soln
(100 mL) were added. The layers were separated and the aq layer
was extracted with CH2Cl2 (3 × 30 mL). The combined organic lay-
ers were washed with brine (30 mL), dried over MgSO4, filtered,
and concentrated in vacuo to afford the crude product as a yellow
solid. Recrystallization from EtOH furnished the title compound as
yellow cotton-like needles (0.91 g, 92%).
13C NMR (151 MHz, DMSO-d6): δ = 159.5, 158.7 (d, J = 249.6
Hz), 155.8, 146.3, 134.0 (d, J = 15.7 Hz), 132.7, 131.5, 119.0,
111.5, 111.0 (d, J = 28.4 Hz), 106.9, 102.6.
GC–MS: tR = 4.356 min, m/z = 249 [M+].
Anal Calcd for C12H8FNO4: C, 57.84; H, 3.24; N, 5.62. Found: C,
57.94; H, 3.25; N, 5.67.
7-Nitrodibenzo[b,d]furan-3-ol (2)
Compound 14 (500 mg, 2.01 mmol) and Cs2CO3 (1.96 g, 6.02
mmol) were dissolved in MeCN (10 mL) and stirred for 30 min at
150 °C under MW irradiation conditions. EtOAc (30 mL) was add-
ed to the mixture and the organic layer was washed with H2O
(2 × 20 mL), dried over MgSO4, filtered and concentrated in vacuo
to afford the crude product as a brown solid. Recrystallization from
MeCN furnished the title compound as pale brown needle-shaped
crystals (360 mg, 78%).
Mp 209–210 °C; Rf = 0.39 (EtOAc–heptane, 1:2).
1H NMR (600 MHz, CDCl3): δ = 9.06 (s, 1 H), 8.28 (dd, J = 8.6, 1.4
Hz, 1 H), 7.95 (m, 2 H), 7.82 (s, 1 H), 7.06 (dd, J = 8.6, 1.8 Hz, 1
H), 3.96 (s, 3 H), 2.94 (s, 3 H).
Mp 248–249 °C; Rf = 0.19 (EtOAc–heptane, 1:2).
IR (ATR): 3427, 2923, 1614, 1560, 1507, 1457, 1320, 1279, 1206,
1130, 1050, 903, 841, 805, 769, 754, 728 cm–1.
13C NMR (151 MHz, CDCl3): δ = 169.7, 161.6, 145.7, 142.1, 137.5,
1H NMR (600 MHz, DMSO-d6): δ = 10.44 (s, 1 H), 8.50 (d, J = 2.0
Hz, 1 H), 8.26 (dd, J = 8.5, 2.0 Hz, 1 H), 8.21 (d, J = 8.5 Hz, 1 H),
8.08 (d, J = 8.5 Hz, 1 H), 7.11 (d, J = 2.1 Hz, 1 H), 6.96 (dd, J = 8.5,
2.1 Hz, 1 H).
131.8, 121.8, 119.4, 118.7, 117.9, 112.4, 112.0, 101.6, 55.8, 27.6.
GC–MS: tR = 5.385 min, m/z = 284 [M+].
Anal Calcd for C15H12N2O4: C, 63.38; H, 4.25; N, 9.85. Found: C,
63.43; H, 4.19; N, 9.88.
13C NMR (151 MHz, DMSO-d6): δ = 160.1, 159.5, 154.1, 144.7,
130.5, 123.2, 119.9, 118.8, 113.6, 113.3, 107.2, 98.1.
GC–MS: tR = 5.451 min, m/z = 229 [M+].
UV/Vis (MeOH): λmax = 356 nm (ε = 20 × 103 M–1·cm–1).
7-Nitro-9H-carbazol-2-ol (3)
Compound 19 (0.300 g, 1.06 mmol) was heated at reflux tempera-
ture in aq HBr (50.0 mL, 8.8 M) soln for 1 h, which gave full con-
version of the starting material. The HBr was evaporated in vacuo,
and EtOAc (20 mL) and brine (100 mL) were added to the mixture.
The layers were separated and the aq layer was extracted with
EtOAc (3 × 20 mL). The combined organic layers were washed
with brine (30 mL), dried over MgSO4, filtered, and concentrated in
vacuo to afford the crude product as a yellow solid. Recrystalliza-
tion from acetone–heptane furnished the title compound as a yellow
solid (190 mg, 79%).
Anal Calcd for C12H7NO4: C, 62.89; H, 3.08; N, 6.11. Found: C,
62.90; H, 3.15; N, 6.09.
N-(2-Bromo-5-nitrophenyl)acetamide (16)
2-Bromo-5-nitroaniline (15) (5.0 g, 23 mmol) and Ac2O (4.35 mL,
46.1 mmol) were dissolved in CH2Cl2 (50 mL) and the mixture was
stirred at r.t. under an Ar atm for 24 h. The product crystallized from
the reaction mixture, and the crystals were isolated and washed with
H2O to yield the title compound as a colorless solid (5.5 g, 92%).
Mp >270 °C; Rf = 0.35 (EtOAc–heptane, 1:1).
IR (ATR): 2923, 1633, 1502, 1457, 1280, 1152, 1070, 830, 804, 738
cm–1.
Mp 183 °C (Lit.8 178–180 °C); Rf = 0.22 (EtOAc–heptane, 1:2).
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2013, 45, 1115–1120

1120
T. H. Jepsen et al.
PAPER
1H NMR (600 MHz, CD3OD): δ = 8.15 (s, 1 H), 7.91 (s, 2 H), 7.84
(d, J = 8.5 Hz, 1 H), 6.77 (d, J = 1.2 Hz, 1 H), 6.68 (m, 1 H).
13C NMR (151 MHz, CD3OD): δ = 159.8, 145.8, 145.5, 140.2,
130.1, 123.2, 119.5, 116.1, 115.1, 111.3, 107.1, 97.4.
GC–MS: tR = 6.012 min, m/z = 228 [M+].
ChemPhysChem 2010, 11, 2495. (e) Wanko, M.;
Houmøller, J.; Støchkel, K.; Kirketerp, M-. B. S.; Petersen,
M. Å.; Nielsen, M. B.; Nielsen, S. B.; Rubio, A. Phys. Chem.
Chem. Phys. 2012, 14, 12905.
(2) Jepsen, T. H.; Larsen, M.; Jørgensen, M.; Solanko, K. A.;
Bond, A. D.; Kadziola, A.; Nielsen, M. B. Eur. J. Org.
Chem. 2011, 53.
UV/Vis (MeOH): λmax = 377 nm (ε = 16 × 103 M–1·cm–1).
(3) Liu, J.; Fitzgerald, A. E.; Mani, N. S. J. Org. Chem. 2008,
73, 2951.
Anal Calcd for C12H8N2O3: C, 63.16; H, 3.53; N, 12.28. Found: C,
63.11; H, 3.54; N, 12.19.
(4) (a) Tsang, W. C. P.; Zheng, N.; Buchwald, S. L. J. Am.
Chem. Soc. 2005, 127, 14560. (b) Jordan-Hore, J. A.;
Johansson, C. C. C.; Moises, G.; Beck, E. M.; Gaunt, M. J.
J. Am. Chem. Soc. 2008, 130, 16184. (c) Tsang, W. C. P.;
Munday, R. H.; Brasche, G.; Zheng, N.; Buchwald, S. L.
J. Org. Chem. 2008, 73, 7603.
Acknowledgment
We acknowledge support from The Danish Council for Independent
Research, Natural Sciences (#10-082088).
(5) For an alternative synthesis of dibenzothiophenes and
carbazoles using palladium-catalyzed tetra-fold Heck
couplings on tetrabromothiophene and N-methyltetra-
bromopyrrole as key reactions, see: Toguem, S.-M. T.;
Knepper, I.; Ehlers, P.; Dang, T. T.; Patonay, T.; Langer, P.
Adv. Synth. Catal. 2012, 354, 1819.
(6) (a) Miyaura, N.; Yamada, K.; Suzuki, A. Tetrahedron Lett.
1979, 36, 3437. (b) Miyaura, N.; Suzuki, A. Chem. Rev.
1995, 95, 2457. (c) Rossi, R.; Bellina, F.; Lessi, M.
Tetrahedron 2011, 67, 6969.
(7) (a) Itoh, T.; Mase, T. Org. Lett. 2004, 6, 4587.
(b) Mispelaere-Canivet, C.; Spindler, J. F.; Perrio, S.;
Beslin, P. Tetrahedron 2005, 61, 5253.
(8) Chandramohan, M. R.; Sardessai, M. S.; Shah, S. R.;
Seshadri, S. Indian J. Chem. 1969, 7, 1006.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
n
nfomartit
References
(1) (a) Muthuraman, M.; Bagieu-Beucher, M.; Masse, R.;
Nicoud, J. F.; Desiraju, G. R. J. Mater. Chem. 1999, 9, 1471.
(b) Muthuraman, M.; Nicoud, J. F.; Masse, R.; Desiraju, G.
R. Mol. Cryst. Liq. Cryst. Sci. Technol., Sect. A 2001, 356, 1.
(c) Kirketerp, M.-B. S.; Petersen, M. Å.; Wanko, M.; Leal,
L. A. E.; Zettergren, H.; Raymo, F. M.; Rubio, A.; Nielsen,
M. B.; Nielsen, S. B. ChemPhysChem 2009, 10, 1207.
(d) Kirketerp, M.-B. S.; Petersen, M. Å.; Wanko, M.;
Zettergren, H.; Rubio, A.; Nielsen, M. B.; Nielsen, S. B.
Synthesis 2013, 45, 1115–1120
© Georg Thieme Verlag Stuttgart · New York