Palladium-Catalyzed Regioselective Direct Arylation of Benzofurazans at the C-4 Position

Article abstract of DOI:10.1002/adsc.201700435

The palladium-catalyzed direct arylation of benzofurazans with aryl bromides to access 4-arylbenzofurazans proceeds in moderate-to-high yields using phosphine-free palladium acetate as the catalyst and potassium acetate as an inexpensive base. A wide variety of (hetero)aryl bromides, including bromopyridine and bromothiophene derivatives has been successfully employed. Palladium-catalyzed one-pot C-4,C-7-diarylation of benzofurazan was also achieved using a larger amount of aryl bromide. Moreover, the derivatization of 4-arylbenzofurazans into 4-arylquinaxolines is also reported. (Figure presented.).

Full text of DOI:10.1002/adsc.201700435

Title: Palladium-Catalyzed Regioselective Direct Arylation of
Benzofurazans at C4 Position
Authors: Imane Idris, Fazia Derridj, Jean-Francois Soulé, and Henri
Doucet
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10.1002/adsc.201700435
Advanced Synthesis & Catalysis
FULL PAPER
DOI: 10.1002/adsc.201((will be filled in by the editorial staff))
Palladium-Catalyzed Regioselective Direct Arylation of
Benzofurazans at C4 Position
Imane Idris,a,b Fazia Derridj,a,b Jean-François Soulé,a*and Henri Doucet a*
a
Institut des Sciences Chimiques de Rennes, UMR 6226 CNRS-Universitꢀ de Rennes 1 “Organometalliques, Mateꢁiaux
́
et Catalyse”, Campus de Beaulieu, 35042 Rennes, France. Fax: (+33)-(0)2-2323-6939, jean-framcois.soule@univ-
rennes1.fr and henri.doucet@univ-rennes1.fr
Laboratoire de physique et chimie des Matériaux (LPCM), UMMTO University, BP 17 RP, 15000 Tizi-Ouzou, Algeria.
b
Received: ((will be filled in by the editorial staff))
Supporting information for this article is available on the WWW under http://dx.doi.org/10.1002/adsc.201######.((Please
delete if not appropriate))
Abstract. The palladium-catalyzed direct arylation of Palladium-catalyzed
one-pot
C4,C7-diarylation
of
benzofurazans with aryl bromides to access 4- benzofurazane was also described using a larger amount of
arylbenzofurazans proceeds in moderate-to-high yields using aryl bromide. Moreover, the derivatization of 4-
phosphine-free palladium acetate as the catalyst and arylbenzofurazans into 4-arylquinaxolines is also reported.
potassium acetate as an inexpensive base. A wide variety of
(hetero)aryl bromides, including bromopyridine and
bromothiophene derivatives has been successfully employed.
Keywords: Benzofurazans; C–H activation; Catalysis;
Palladium; Quinaxolines.
One of the most common access to 4-
Introduction
arylbenzofurazan
derivatives
is
through
a
bromination of benzofurazan followed by palladium
catalyzed Suzuki[5] or Stille[6] cross-coupling
reactions (Scheme 1a). Oligomers have also been
synthetized from 4,7-dibromofurazan and an
organometallic reagent.[7] Negishi reactions with an
organozinc reagent prepared from benzofurazan
Benzofurazan is an important unit, which found
applications in materials sciences. Especially C4
or/and C7 (hetero)aryl benzofurazans are involved in
the molecular design of photovoltaic materials
(Figure 1).[1]
Some 4-arylbenzofurazans also
displayed important biological activities such as I,
which inhibits the PAS‐B domain of the hypoxia
through
a
magnesiation
with
bis(2,2,6,6-
tetramethylpiperidin-1-yl)magnesium–lithium
inducible
factor
2α;[2]
or
the
chloride complex (TMP2Mg·2LiCl) followed by
transmetalation with zinc chloride, have also been
reported (Scheme 1b).[8] Since the discovery by
Nakamura[9] and Otha[10] of the Pd-catalyzed C–H
bond arylation of heteroarenes using aryl halides, this
technology has emerged as one of the most powerful
method for the formation of C–C bonds for the access
to a wide variety of arylated heterocycles as no
benzo[c][1,2,5]oxadiazole-1-oxide II, which has been
synthetized for its antimicrobial properties.[3]
Recently, electron donor–acceptor type organic
semiconductors were designed based on 4-
heteroarylbenzofurazan (Th-BO-Th) for application
as organo-photocatalysts (Figure 1).[4]
prefunctionalization is required.[11]
However,
examples of palladium-catalyzed non-directed C–H
bond arylation of 6-membered rings remains
scarce.[12] Recent examples on the arylation of
activated benzothiadiazole via C–H bond activation
have been reported using palladium catalysis.[13] To
the best of our knowledge there is no example of
direct arylation of benzofurazan in the literature, to
date (Scheme 1c).
Figure 1. Examples of Useful Molecules Containing a 4-
Arylbenzofurazan Unit.
1
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10.1002/adsc.201700435
Advanced Synthesis & Catalysis
source (Table 1, entry 14). It should also be
mentioned that using the optimized reaction
conditions, benzothiadiazole was unreactive.
Table 1. Optimization of the Reaction Conditions
Pd
Solve Conv. Yield
nt
(%)[a] in 1 (%)[a]
Entry
1
Base
(x mol%)
PdCl(C3H5)
(dppb) (2)
PdCl(C3H5)
(dppb) (2)
Pd(OAc)2
(2)
KOAc DMA 100
KOAc DMA 100
KOAc DMA 100
75
74
82
2[b]
3
Scheme 1. Previous Strategies to Synthetize 4-
Arylbenzofurazans.
Pd(OAc)2
(1)
4
KOAc DMA 100
85
As part of our continuing efforts concerning the
functionalization of benzene rings fused to
heterocycles via palladium-catalyzed C–H bond
arylation, we recently reported an efficient protocol
for the synthesis of benzothiazoles and benzoxazoles
arylated at the C7 position.[14] Based on these results,
we examined the reactivity of benzofurazan in
palladium-catalyzed direct arylation using aryl
bromides as aryl source.
Pd(OAc)2
(0.5)
Pd(OAc)2
(1)
5
6
KOAc DMA
PivOK DMA
K2CO3 DMA
Cs2CO3 DMA
83
80
95
67
79
53
12
0
Pd(OAc)2
(1)
7
Pd(OAc)2
(1)
8
Pd(OAc)2
9[b]
10[b,c]
11[b]
12[b]
13[b]
14[d]
KOAc DMA 100
87
89
0
(1)
Pd(OAc)2
(1)
KOAc DMA 100
CPM
Results and Discussion
Pd(OAc)2
KOAc
KOAc
KOAc
0
0
0
0
(1)
E
Pd(OAc)2
(1)
pentan-
1-ol
We began our investigations by fine-tuning the
0
conditions
using
benzofurazan
and
4-
Pd(OAc)2
(1)
Pd(OAc)2
(1)
bromobenzonitrile as model substrates in 1.5:1 ratio
(Table 1). We were pleased to find that the reaction
occurred regioselectively at the C4 position to afford
1 in good yields using 2 mol% of a diphosphine-
palladium catalyst in the presence of KOAc as base in
DMA at 150 ºC or even at 120 ºC (Table 1, entries 1
and 2). More interestingly, we found that the reaction
is also operative using 2 mol% of phosphine-free
Pd(OAc)2 catalyst in a comparable yield (Table 1,
entry 3). A lower catalyst loading of 1 mol% of
Pd(OAc)2 gave 1 in 85% yield; while partial
conversion was obtained if only 0.5 mol% catalyst
loading was used (Table 1, entries 4 and 5). Other
inorganic bases, such as PivOK, K2CO3 or Cs2CO3
did not allow to improve the yield in 1 (Table 1,
entries 6-8). When the reaction was performed using
1 mol% Pd(OAc)2 at 120 ºC, the C4-arylated
benzofurazan 1 was obtained in 87% yield (Table 1,
entry 9). Under these conditions, the excess of
benzofurazan can be decreased up to 1.15 equivalents,
as the desired product 1 was isolated in 89% yield
(Table 1, entry 10). Then, we employed greener
solvents than DMA such as cyclopentylmethyl ether,
1-pentanol or diethylcarbonate,[15] but no reaction
occurred (Table 1, entries 11-13). No reaction
occurred when 4-chlorobenzonitrile was used as aryl
DEC
0
KOAc DMA
0
[a] Determined by GC-MS analysis using dodecane as
internal standard. [b] Reaction performed at 120 ºC. [c]
Reaction performed using 1.15 equiv. of benzofurazan. [d]
4-Chlorobenzonitrile was used instead of 4-
bromobenzonitrile. DMA = Dimethylacetamide; CPME =
Cyclopentylmethyl ether; DEC = Diethylcarbonate
With the best conditions in hands, namely 1 mol%
phosphine-free Pd(OAc)2 associated to KOAc as base
in DMA at 120 ºC, we turned our attention to the
scope of the reaction (Scheme 2). First, we examined
the reactivity of para-substituted aryl bromides. The
coupling of benzofurazan with 4-bromonitrobenzene,
4-bromobenzaldehyde, 4-bromopropiophenone, and
ethyl 4-bromobenzoate proceeded nicely to afford 2–
5 in 69–83% yields. A moderate yield in the desired
4-aryl benzofurazan 6 was obtained from the less
electron-deficient 4-bromochlorobenzene owing a
partial conversion of this aryl bromide.
For
bromobenzene and electron-rich 4-bromoanisole, as
their oxidative addition to palladium is more
challenging,[16] the reactions were conducted at a
more elevated temperature of 150 ºC to afford the
2
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10.1002/adsc.201700435
Advanced Synthesis & Catalysis
desired products 7 and 8 in 65% and 62% yields,
respectively. It should be noted that no additional
phosphine ligand is required to perform such
couplings. The electron-deficient meta-substituted
substituted by an electron-donating group such as a
methoxy at C5 position underwent Pd(OAc)2-
catalyzed direct arylation.
The reaction was
completely regioselective with 4-bromobenzonitrile
or 3-chlorobromobenzene and the arylation took
place exclusively at the C4 position to afford
products 20 and 21 in 68% and 56% yields,
respectively (Scheme 3a). Conversely, the reaction
was not regioselective using 2-bromonitrobenzene,
probably because of its greater steric hindrance. The
major regioisomer 22a was isolated in 38% yield and
resulted from the C–H bond activation at the less
sterically hindered C7 position of the benzofurazan
(Scheme 1b); whereas, the C4-arylation regioisomer
22b was formed in less than 11% yield, making its
aryl
bromides
3-bromobenzonitrile,
and
3-
3-
(trifluoromethyl)bromobenzene
bromonitrobenzene were also very reactive using 1
mol% Pd(OAc)2 as the catalyst at 120 ºC and
afforded 9–11 in yields of 71–79%. Then, we
investigated the effect of an ortho substituent on the
aryl bromide. 2-Nitrile-, 2-formyl-, and 2-fluoro-
bromobenzenes allowed the formation of the desired
4-arylated benzofurazans 12–14 in good yields.
Under the standard reaction conditions, more
sterically demanding 1-bromonaphthalene was also
efficiently coupled with benzofurazan to deliver 15 in
57% yield. N-containing heteroaryl bromides (e.g.,
isolation difficult.
In contrast, benzofurazans
substituted by an electron-withdrawing group such as
5-bromobenzofurazan or 4-nitrobenzofurazan were
not reactive under our reaction conditions, even at
150 ºC or in the presence of PdCl(C3H5)(dppb)
catalyst (Scheme 3c and 3d).
2-bromo-6-(trifluoromethyl)pyridine,
3-
bromoquinoline, or 2-bromo-6-methoxypyridine)
nicely reacted in the presence of 1 mol% Pd(OAc)2 at
150 ºC to afford the desired products 16–18 in good
yields. In addition, this methodology allowed the
synthesis 4-thiophen-2-ylfurazan 19, which is a
useful intermediate in the design of organic materials,
in 63% yield.
Scheme 3. Reactivities of Substituted Benzofurazans in
Palladium-Catalyzed Direct Arylation.
Using the same reaction conditions, but in the
presence of an excess amount of aryl bromides and
base (3 equivalents), benzofurazan has been
diarylated at both C4 and C7 carbons in one pot
(Scheme
4).
From
bromobenzene,
and
4-
3,5-
Scheme 2. Scope of Aryl Bromides in Palladium-
Catalyzed Direct C4 Arylation of Benzofurazan. [a] 4-
chlorobromobenzene
bis(trifluoromethyl)bromobenzene the diarylated
products 23–26 were isolated in a range of yield of
57–72%. Again, it is important to note that this
procedure did not required the use of a phosphine
ligand.
Chloronitrobenzene
bromonitrobenzene. [b] Reaction performed at 150 ºC.
was
used
instead
of
4-
Next, we investigated the reactivity of 4- and 5-
substituted benzofurazans (Scheme 3). Benzofurazan
3
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10.1002/adsc.201700435
Advanced Synthesis & Catalysis
and sulfur or nitrogen containing heteroaromatic
substrates have also been employed successfully. In
addition, some of these 4-arylated benzofurazans
were successfully transformed into quinoxaline
derivatives.
Experimental Section
General Methods: All reactions were carried out under
argon atmosphere with standard Schlenk techniques.
DMA was purchased from Acros Organics and were not
purified before use. Benzofurazans were purchased from
Sigma-Aldrich. 1H NMR spectra were recorded on Bruker
GPX (400 MHz) spectrometer. Chemical shifts (δ) were
reported in parts per million relative to residual chloroform
(7.28 ppm for 1H; 77.23 ppm for 13C), constants were
Scheme 4. Scope of Palladium-Catalyzed C4,C7
Diarylation of Benzofurazan
1
reported in Hertz. H NMR assignment abbreviations were
It is known that furazan unit of benzofurazans can
easily undergo a ring opening in the presence of
ethanolamines under acidic conditions to yield
the following: singlet (s), doublet (d), triplet (t), quartet (q),
doublet of doublets (dd), doublet of triplets (dt), and
multiplet (m). 13C NMR spectra were recorded at 100
MHz on the same spectrometer and reported in ppm. All
reagents were weighed and handled in air.
quinoxaline derivatives.[17]
Quinoxaline is an
important motif, which is present in many
pharmaceuticals.[18] Therefore, we investigated the
synthesis of some quinoxalines from arylated
benzofurazans. Using the Samsonov conditions,[17]
namely, 10 mol% para-toluenesulfonic acid in the
Procedure A (Palladium-catalyzed direct C4 arylation):
To a 5 mL oven dried Schlenk tube, benzofurazan
derivative (1.15 mmol), aryl bromide (1 mmol), AcOK
(196 mg, 2 mmol), DMA (4 mL) and Pd(OAc)2 (2.2 mg,
0.01 mmol, 2 mol%) were successively added. The
reaction mixture was evacuated by vacuum-argon cycles (5
times) and stirred at 120-150 °C (oil bath temperature) for
16 hours (see tables and schemes). After cooling the
reaction at room temperature and concentration, the crude
mixture was purified by silica column chromatography to
afford the desired arylated products.
presence
of
1-aminoethanol,
the
arylated
benzofurazans 6, 15 and 25 were converted into 5-
aryl quinoxalines 27-29 in 82-87% yields.
4-(Benzo[c][1,2,5]oxadiazol-4-yl)benzonitrile (1):
Following the general procedure
A
using 4-
bromobenzonitrile (182 mg, 1 mmol) and benzofurazan
(138 mg, 1.15 mmol), the residue was purified by flash
chromatography on silica gel (pentane-CH2Cl2, 60-40) to
afford the desired compound 1 (197 mg, 89%) as a white
solid (Mp = 180-184 ºC). 1H NMR (400 MHz, CDCl3) δ
(ppm) 8.13 (d, J = 8.5 Hz, 2H), 7.91 (d, J = 8.9 Hz, 1H),
7.82 (d, J = 8.5 Hz, 2H), 7.66 (d, J = 7.0 Hz, 1H), 7.56 (dd,
J = 7.0, 9.0 Hz, 1H).13C NMR (100 MHz, CDCl3) δ (ppm)
149.7, 148.1, 139.4, 132.7, 131.6, 129.3, 128.9, 128.4,
118.5, 116.8, 112.8.Elemental analysis: calcd (%) for
C13H7N3O (221.22): C 70.58, H 3.19; found: C 70.85, H
3.46.
Scheme 5. Synthesis of 5-Arylated cc from Arylated
Benzofurazans
Conclusion
4-(4-Nitrophenyl)benzo[c][1,2,5]oxadiazole
(2):
Following the general procedure using 4-
A
In summary, we disclose here an elegant route to
access 4-arylated benzofurazans from commercially
available benzofurazan through palladium-catalyzed
regioselective C–H bond arylation. Our phosphine-
free procedure using Pd(OAc)2 catalyst, KOAc as
inexpensive base in the presence of aryl bromides as
coupling partners promotes the C4 arylation or the
C4,C7-diarylation of benzofurazan depending of the
aryl bromide stoichiometry. A wide range of
functions such as methoxy, fluoro, formyl, propionyl,
carboxylate, nitrile or nitro on the aryl bromide is
tolerated. Some sterically hindered aryl bromides,
bromonitrobenzene (202 mg, 1 mmol) and benzofurazan
(138 mg, 1.15 mmol), the residue was purified by flash
chromatography on silica gel (pentane-EtOAc, 90-10) to
afford the desired compound 2 (200 mg, 83%) as a yellow
1
solid (MP = 198-202 ºC). H NMR (400 MHz, CDCl3) δ
(ppm) 8.42 (d, J = 8.9 Hz, 2H), 8.23 (d, J = 8.9 Hz, 2H),
7.96 (d, J = 9.0 Hz, 1H), 7.73 (d, J = 6.8 Hz, 1H), 7.60 (dd,
J = 6.8, 9.0 Hz, 1H).
13C NMR (100 MHz, CDCl3) δ (ppm) 149.7, 148.2, 148.1,
141.2, 131.5, 129.7, 129.2, 128.1, 124.2, 117.1.Elemental
analysis: calcd (%) for C12H7N3O3 (241.21): C 59.75, H
2.93; found: C 59.81, H 3.19.
4
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10.1002/adsc.201700435
Advanced Synthesis & Catalysis
4-(Benzo[c][1,2,5]oxadiazol-4-yl)benzaldehyde (3):
Following the general procedure using 4-
7.46 (m, 4H).13C NMR (100 MHz, CDCl3) δ (ppm) 149.8,
148.6, 135.3, 131.8, 130.5, 129.3, 129.0, 128.4, 128.0,
115.0. Elemental analysis: calcd (%) for C12H8N2O
(196.21): C 73.46, H 4.11; found: C 73.69, H 3.90.
A
bromobenzaldehyde (185 mg, 1 mmol) and benzofurazan
(138 mg, 1.15 mmol), the residue was purified by flash
chromatography on silica gel (pentane-Et2O, 70-30) to
afford the desired compound 3 (166 mg, 74%) as a pale
4-(4-methoxyphenyl)benzo[c][1,2,5]oxadiazole (8):
Following the general procedure A using 4-bromoanisole
(187 mg, 1 mmol) and benzofurazan (138 mg, 1.15 mmol),
the residue was purified by flash chromatography on silica
gel (pentane-toluene, 80-20) to afford the desired
compound 8 (140 mg, 62%) as an orange solid (MP = 118-
121 ºC). 1H NMR (400 MHz, CDCl3) δ (ppm) 8.00 (d, J =
8.8 Hz, 2H), 7.77 (dd, J = 1.3, 8.5 Hz, 1H), 7.58 – 7.47 (m,
2H), 7.08 (d, J = 8.8 Hz, 2H), 3.92 (s, 3H).13C NMR (100
MHz, CDCl3) δ (ppm) 160.5, 149.9, 148.7, 131.9, 130.1,
129.7, 127.7, 126.7, 114.4, 114.1, 55.4. This is a known
compound and the spectral data are identical to those
reported in literature.[5a]
1
yellow solid (MP = 128-130 ºC). H NMR (400 MHz,
CDCl3) δ (ppm) 10.14 (s, 1H), 8.22 (d, J = 8.4 Hz, 2H),
8.07 (d, J = 8.4 Hz, 2H), 7.93 (d, J = 9.0 Hz, 1H), 7.72 (d,
J = 6.8 Hz, 1H), 7.58 (dd, J = 6.8, 9.0 Hz, 1H).13C NMR
(100 MHz, CDCl3) δ (ppm) 191.6, 149.8, 148.3, 140.9,
136.5, 131.6, 130.2, 129.3, 129.1, 129.0, 116.5.Elemental
analysis: calcd (%) for C13H8N2O2 (224.21): C 69.64, H
3.60; found: C 69.52, H 3.75.
1-(4-(Benzo[c][1,2,5]oxadiazol-4-
yl)phenyl)propan-1-one (4): Following the general
procedure A using 4-bromopropiophenone (213 mg, 1
mmol) and benzofurazan (138 mg, 1.15 mmol), the residue
was purified by flash chromatography on silica gel
(pentane-CH2Cl2, 50-50) to afford the desired compound 4
3-(Benzo[c][1,2,5]oxadiazol-4-yl)benzonitrile (9):
Following the general procedure
A
using 3-
bromobenzonitrile (182 mg, 1 mmol) and benzofurazan
(138 mg, 1.15 mmol), the residue was purified by flash
chromatography on silica gel (pentane-toluene, 80-20) to
afford the desired compound 9 (157 mg, 71%) as a yellow
1
(174 mg, 69%) as a white solid (MP = 161-165 ºC). H
NMR (400 MHz, CDCl3) δ (ppm) 8.14 (s, 4H), 7.90 (d, J =
9.0 Hz, 1H), 7.69 (d, J = 6.8 Hz, 1H), 7.57 (dd, J = 6.8, 9.0
Hz, 1H), 3.09 (q, J = 7.3 Hz, 2H), 1.29 (t, J = 7.2 Hz,
3H).13C NMR (100 MHz, CDCl3) δ (ppm) 200.2, 149.8,
148.4, 139.3, 137.1, 131.6, 129.3, 128.9, 128.6, 128.5,
116.1, 32.0, 8.2.Elemental analysis: calcd (%) for
C15H12N2O2 (252.27): C 71.42, H 4.79; found: C 71.56, H
3.81.
1
solid (MP = 156-159 ºC). H NMR (400 MHz, CDCl3) δ
(ppm) δ 8.34 – 8.24 (m, 2H), 7.92 (d, J = 8.9 Hz, 1H), 7.78
(dt, J = 1.4, 7.7 Hz, 1H), 7.69 (d, J = 7.8 Hz, 1H), 7.67 –
7.63 (m, 1H), 7.58 (dd, J = 6.8, 8.9 Hz, 1H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 149.7, 148.2, 136.4, 132.6,
132.5, 131.8, 131.6, 129.9, 128.9, 128.1, 118.4, 116.5,
113.4. Elemental analysis: calcd (%) for C13H7N3O
(221.22): C 70.58, H 3.19; found: C 70.41, H 3.29.
4-(3-
Ethyl
4-(benzo[c][1,2,5]oxadiazol-4-yl)benzoate
(5): Following the general procedure A using ethyl 4-
bromobenzoate (229 mg, 1 mmol) and benzofurazan (138
mg, 1.15 mmol), the residue was purified by flash
chromatography on silica gel (pentane-CH2Cl2, 40-60) to
afford the desired compound 5 (188 mg, 70%) as an orange
(Trifluoromethyl)phenyl)benzo[c][1,2,5]oxadiazole
(10): Following the general procedure A using 1-bromo-3-
(trifluoromethyl)benzene (225 mg,
1
mmol) and
1
solid (MP = 105-108 ºC). H NMR (400 MHz, CDCl3) δ
benzofurazan (138 mg, 1.15 mmol), the residue was
purified by flash chromatography on silica gel (pentane-
toluene, 90-10) to afford the desired compound 10 (209
(ppm) 8.22 (d, J = 8.2 Hz, 2H), 8.11 (d, J = 8.2 Hz, 2H),
7.89 (d, J = 9.0 Hz, 1H), 7.68 (d, J = 6.8 Hz, 1H), 7.56 (dd,
J = 6.8, 9.0 Hz, 1H), 4.45 (q, J = 7.1 Hz, 2H), 1.46 (t, J =
7.1 Hz, 3H).13C NMR (100 MHz, CDCl3) δ (ppm) 166.1,
149.8, 148.4, 139.3, 131.6, 131.0, 130.1, 129.4, 128.9,
128.3, 116.0, 61.2, 14.4.
1
mg, 79%) as pale yellow oil. H NMR (400 MHz, CDCl3)
δ (ppm) 8.28 – 8.24 (m, 2H), 7.90 (d, J = 8.9 Hz, 1H), 7.77
– 7.73 (m, 1H), 7.70 (d, J = 7.9 Hz, 1H), 7.67 (d, J = 6.8
Hz, 1H), 7.57 (dd, J = 6.8, 9.0 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ (ppm) 149.7, 148.4, 135.9, 131.7, 131.6,
131.5 (q, J = 32.8 Hz), 129.5, 129.0, 128.7, 125.9 (q, J =
4.1 Hz),125.0 (q, J = 4.1 Hz), 123.9 (q, J = 272.4), 116.1.
Elemental analysis: calcd (%) for C13H7F3N2O (264.21): C
59.10, H 2.67; found: C 59.33, H 2.51.
Elemental analysis: calcd (%) for C15H12N2O3 (268.27): C
67.16, H 4.51; found: C 66.98, H 4.79.
4-(4-Chlorophenyl)benzo[c][1,2,5]oxadiazole (6):
Following the general procedure A using 1-bromo-4-
chlorobenzene (191 mg, 1 mmol) and benzofurazan (138
mg, 1.15 mmol), the residue was purified by flash
chromatography on silica gel (pentane- CH2Cl2, 80-20) to
afford the desired compound 6 (111 mg, 48%) as a yellow
solid (MP = 95-97 ºC). 1H NMR (400 MHz, CDCl3) δ
(ppm) 7.98 (d, J = 8.5 Hz, 2H), 7.85 (d, J = 8.9 Hz, 1H),
7.59 (d, J = 6.8 Hz, 1H), 7.57 – 7.44 (m, 3H).13C NMR
(100 MHz, CDCl3) δ (ppm) 149.8, 148.4, 135.4, 133.6,
131.7, 129.6, 129.2, 129.2, 128.0, 115.5. Elemental
analysis: calcd (%) for C12H7ClN2O (230.65): C 62.49, H
3.06; found: C 62.53, H 3.00.
4-(Phenyl)benzo[c][1,2,5]oxadiazole (7): Following
the general procedure A using bromobenzene (157 mg, 1
mmol) and benzofurazan (138 mg, 1.15 mmol), the residue
was purified by flash chromatography on silica gel
(pentane-toluene, 80-20) to afford the desired compound 7
(127 mg, 65%) as a yellow solid (MP = 58-60 ºC). 1H
NMR (400 MHz, CDCl3) δ (ppm) 8.04 – 7.98 (m, 2H),
7.87 – 7.80 (m, 1H), 7.60 (td, J = 1.0, 6.8 Hz, 1H), 7.57 –
4-(3-Nitrophenyl)benzo[c][1,2,5]oxadiazole (11):
Following the general procedure
A
using 3-
bromonitrobenzene (202 mg, 1 mmol) and benzofurazan
(138 mg, 1.15 mmol), the residue was purified by flash
chromatography on silica gel (pentane-EtOAc, 90-1510 to
afford the desired compound 11 (171 mg, 71%) as a brown
1
solid (MP = 150-153 ºC). H NMR (400 MHz, CDCl3) δ
(ppm) 8.86 (s, 1H), 8.45 (d, J = 7.5 Hz, 1H), 8.35 (d, J =
7.9 Hz, 1H), 7.94 (d, J = 9.1 Hz, 1H), 7.81 – 7.68 (m, 2H),
7.64 – 7.53 (m, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm)
149.7, 148.8, 148.2, 136.7, 134.4, 131.6, 130.1, 129.1,
127.9, 123.8, 123.0, 116.7. Elemental analysis: calcd (%)
for C12H7N3O3 (241.21): C 59.75, H 2.93; found: C 59.98,
H 3.07.
2-(Benzo[c][1,2,5]oxadiazol-4-yl)benzonitrile (12):
Following the general procedure
A
using 2-
bromobenzonitrile (182 mg, 1 mmol) and benzofurazan
(138 mg, 1.15 mmol), the residue was purified by flash
5
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700435
Advanced Synthesis & Catalysis
chromatography on silica gel (pentane-CH2Cl2, 60-40) to
7.97 (dd, J = 0.8, 8.9 Hz, 1H), 7.74 (dd, J = 0.9, 7.8 Hz,
1H), 7.64 (dd, J = 6.9, 9.0 Hz, 1H).
afford the desired compound 12 (148 mg, 67%) as a white
1
solid (MP = 164-166 ºC). H NMR (400 MHz, CDCl3) δ
13C NMR (100 MHz, CDCl3) δ (ppm) 152.1, 149.9, 148.3
(q, J = 34.9 Hz), 147.7, 138.8, 131.9, 131.2, 126.8, 126.5,
121.4 (q, J = 274.7 Hz), 119.9, 117.7. Elemental analysis:
calcd (%) for C12H6F3N3O (265.20): C 54.35, H 2.28;
found: C 64.43, H 2.37.
(ppm) 7.97 (d, J = 9.1 Hz, 1H), 7.93 (d, J = 7.8 Hz, 1H),
7.90 (d, J = 7.2 Hz, 1H), 7.79 (dt, J = 1.4, 7.7 Hz, 1H),
7.72 (d, J = 6.7 Hz, 1H), 7.65 – 7.57 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 149.5, 148.6, 138.7, 134.1,
133.0, 131.7, 131.4, 131.1, 129.3, 126.9, 118.0, 117.0,
111.7. Elemental analysis: calcd (%) for C13H7N3O
(221.22): C 70.58, H 3.19; found: C 70.39, H 3.30.
4-(Quinolin-3-yl)benzo[c][1,2,5]oxadiazole
(17):
Following the general procedure using 3-
A
bromoquinoline (208 mg, 1 mmol) and benzofurazan (138
mg, 1.15 mmol), the residue was purified by flash
chromatography on silica gel (pentane-EtOAc, 70-30) to
afford the desired compound 17 (200 mg, 81%) as an
2-(Benzo[c][1,2,5]oxadiazol-4-yl)benzaldehyde
(13): Following the general procedure A using 2-
bromobenzaldehyde (185 mg, 1 mmol) and benzofurazan
(138 mg, 1.15 mmol), the residue was purified by flash
chromatography on silica gel (pentane-Et2O, 70-30) to
afford the desired compound 13 (141 mg, 63%) as an
1
orange solid (MP = 143-145 ºC). H NMR (400 MHz,
DMSO-d6) δ (ppm) 9.53 (d, J = 2.4 Hz, 1H), 9.06 (d, J =
2.0 Hz, 1H), 8.18 – 8.10 (m, 4H), 7.87 (ddd, J = 1.4, 6.9,
8.4 Hz, 1H), 7.81 (dd, J = 6.8, 9.0 Hz, 1H), 7.72 (ddd, J =
1.2, 6.9, 8.1 Hz, 1H). 13C NMR (100 MHz, DMSO-d6) δ
(ppm) 150.1, 150.0, 148.7, 147.8, 135.9, 133.6, 131.0,
130.9, 129.3, 129.2, 128.3, 127.9, 127.7, 126.3, 116.3.
Elemental analysis: calcd (%) for C15H9N3O (247.26): C
72.87, H 3.67; found: C 72.98, H 3.54.
1
orange solid (MP = 140-143 ºC). H NMR (400 MHz,
CDCl3) δ (ppm) 9.97 (s, 1H), 8.12 (d, J = 7.9 Hz, 1H), 7.94
(d, J = 9.0 Hz, 1H), 7.77 (dt, J = 1.5, 7.5 Hz, 1H), 7.71 –
7.63 (m, 2H), 7.57 (dd, J = 6.6, 9.1 Hz, 1H), 7.36 (d, J =
6.6 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ (ppm) 190.8,
149.6, 149.1, 138.1, 134.4, 133.9, 131.8, 131.3, 131.2,
129.7, 129.5, 128.0, 116.4. Elemental analysis: calcd (%)
for C13H8N2O2 (224.21): C 69.64, H 3.60; found: C 69.72,
H 3.88.
4-(6-Methoxypyridin-2-
yl)benzo[c][1,2,5]oxadiazole (18): Following the general
procedure A using 2-bromo-6-methoxypyridine (188 mg, 1
mmol) and benzofurazan (138 mg, 1.15 mmol), the residue
was purified by flash chromatography on silica gel
(pentane-toluene, 90-10) to afford the desired compound
18 (130 mg, 57%) as a yellow solid (MP = 140-143 ºC). 1H
NMR (400 MHz, CDCl3) δ (ppm) 8.53 (d, J = 6.9 Hz, 1H),
8.32 (d, J = 7.5 Hz, 1H), 7.89 (d, J = 8.9 Hz, 1H), 7.79 (dd,
J = 7.4, 8.3 Hz, 1H), 7.60 (dd, J = 6.9, 9.0 Hz, 1H), 6.85
(d, J = 8.3 Hz, 1H), 4.09 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ (ppm) 163.5, 150.0, 148.8, 147.9, 139.6, 131.8,
129.5, 128.1, 117.7, 116.4, 111.7, 53.3. Elemental analysis:
calcd (%) for C12H9N3O2 (227.22): C 63.43, H 3.99; found:
C 63.68, H 4.13.
4-(2-Fluorophenyl)benzo[c][1,2,5]oxadiazole (14):
Following the general procedure A using 1-bromo-2-
fluorobenzene (175 mg, 1 mmol) and benzofurazan (138
mg, 1.15 mmol), the residue was purified by flash
chromatography on silica gel (pentane-toluene, 90-10) to
afford the desired compound 14 (167 mg, 78%) as a yellow
1
solid (MP = 119-121 ºC). H NMR (400 MHz, CDCl3) δ
(ppm) 7.91 – 7.84 (m, 2H), 7.62 (d, J = 6.9 Hz, 1H), 7.54
(dd, J = 6.8, 9.0 Hz, 1H), 7.51 – 7.44 (m, 1H), 7.34 (td, J =
1.2, 7.6 Hz, 1H), 7.30 – 7.24 (m, 1H). 13C NMR (100
MHz, CDCl3) δ (ppm) 159.9 (d, J = 249.5 Hz), 149.5,
148.7, 131.5, 131.2 (d, J = 5.4 Hz), 130.8 (d, J = 8.6 Hz),
124.9, 124.5, 124.5, 123.1 (d, J = 12,8 Hz), 116.4 (d, J =
20.9 Hz), 115.8. Elemental analysis: calcd (%) for
C12H7FN2O (214.20): C 67.29, H 3.29; found: C 67.18, H
3.45.
1-(5-(Benzo[c][1,2,5]oxadiazol-4-yl)thiophen-2-
yl)ethan-1-one (19): Following the general procedure A
using 1-(5-bromothiophen-2-yl)ethan-1-one (205 mg, 1
mmol) and benzofurazan (138 mg, 1.15 mmol), the residue
was purified by flash chromatography on silica gel
(pentane-EtOAc, 80-20) to afford the desired compound 19
4-(Naphthalen-1-yl)benzo[c][1,2,5]oxadiazole (15):
Following the general procedure
A
using 1-
1
bromonaphthalene (207 mg, 1 mmol) and benzofurazan
(138 mg, 1.15 mmol), the residue was purified by flash
chromatography on silica gel (pentane-toluene, 95-15) to
afford the desired compound 15 (140 mg, 57%) as a yellow
(154 mg, 63%) as a yellow solid (MP = 205-207 ºC). H
NMR (400 MHz, CDCl3) δ (ppm) 8.17 (d, J = 4.0 Hz, 1H),
7.90 – 7.83 (m, 1H), 7.78 (d, J = 4.0 Hz, 1H), 7.75 (d, J =
6.8 Hz, 1H), 7.51 (dd, J = 6.8, 9.0 Hz, 1H), 2.64 (s, 3H).
13C NMR (100 MHz, CDCl3) δ (ppm) 190.6, 149.5, 147.3,
145.1, 144.7, 133.3, 131.6, 129.8, 127.6, 123.3, 116.3,
26.8. Elemental analysis: calcd (%) for C12H8N2O2S
(244.26): C 59.01, H 3.30; found: C 58.87, H 3.11.
1
solid (MP = 68-71 ºC). H NMR (400 MHz, CDCl3) δ
(ppm) 8.03 – 7.96 (m, 2H), 7.94 (d, J = 8.9 Hz, 1H), 7.74
(d, J = 8.9 Hz, 1H), 7.69 – 7.63 (m, 1H), 7.63 – 7.56 (m,
2H), 7.55 – 7.50 (m, 2H), 7.50 – 7.43 (m, 1H). 13C NMR
(100 MHz, CDCl3) δ (ppm) 149.9, 149.5, 133.9, 133.5,
131.6, 131.6, 131.3, 130.1, 129.5, 128.6, 127.9, 126.6,
126.2, 125.3, 125.3, 115.5. Elemental analysis: calcd (%)
for C16H10N2O (246.27): C 78.03, H 4.09; found: C 78.45,
H 4.19.
4-(5-Methoxybenzo[c][1,2,5]oxadiazol-4-
yl)benzonitrile (20): Following the general procedure A
using 4-bromobenzonitrile (182 mg, 1 mmol) and 6-
methoxybenzofurazan (173 mg, 1.15 mmol), the residue
was purified by flash chromatography on silica gel
(pentane-Et2O, 60-40) to afford the desired compound 20
4-(6-(Trifluoromethyl)pyridin-2-
1
yl)benzo[c][1,2,5]oxadiazole (16): Following the general
procedure A using 2-bromo-6-(trifluoromethyl)pyridine
(225 mg, 1 mmol) and benzofurazan (138 mg, 1.15 mmol),
the residue was purified by flash chromatography on silica
gel (pentane-toluene, 80-20) to afford the desired
compound 16 (188 mg, 71%) as a yellow solid (MP = 148-
150 ºC). 1H NMR (400 MHz, CDCl3) δ (ppm) 8.89 (d, J =
8.0 Hz, 1H), 8.64 (d, J = 6.9 Hz, 1H), 8.15 – 8.05 (m, 1H),
(172 mg, 68%) as an orange solid (MP = 195-197 ºC). H
NMR (300 MHz, CD2Cl2) δ (ppm) 8.02 – 7.89 (m, 3H),
7.81 (d, J = 8.7 Hz, 2H), 7.58 (d, J = 9.8 Hz, 1H), 4.02 (s,
3H). 13C NMR (100 MHz, CD2Cl2) δ (ppm) 156.4, 150.0,
146.9, 137.3, 131.8, 131.0, 123.6, 118.7, 117.9, 111.5,
110.0, 57.6. Elemental analysis: calcd (%) for C14H9N3O2
(251.25): C 66.93, H 3.61; found: C 67.05, H 3.88.
6
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700435
Advanced Synthesis & Catalysis
4-(3-Chlorophenyl)-5-
(ppm) 8.02 (d, J = 8.3 Hz, 4H), 7.69 (s, 2H), 7.55 (d, J =
8.3 Hz, 4H).
methoxybenzo[c][1,2,5]oxadiazole (21): Following the
general procedure A using 1-bromo-3-chlorobenzene (191
mg, 1 mmol) and 6-methoxybenzofurazan (173 mg, 1.15
mmol), the residue was purified by flash chromatography
on silica gel (pentane-Et2O, 90-10) to afford the desired
compound 21 (169 mg, 65%) as a yellow solid (MP = 76-
13C NMR (100 MHz, CDCl3) δ (ppm) 149.0, 135.4, 133.5,
129.6, 129.2, 128.5, 128.0. Elemental analysis: calcd (%)
for C18H10Cl2N2O (341.19): C 63.37, H 2.95; found: C
63.18, H 3.09.
4,7-Bis(3,5-
1
79 ºC). H NMR (400 MHz, CDCl3) δ (ppm) 7.89 (d, J =
bis(trifluoromethyl)phenyl)benzo[c][1,2,5] oxadiazole
(25): Following the general procedure B using 1-bromo-
3,5-bis(trifluoromethyl)benzene (879 mg, 3 mmol) and
benzofurazan (120 mg, 1 mmol), the residue was purified
by flash chromatography on silica gel (pentane-toluene,
90-10) to afford the desired compound 25 (392 mg, 72%)
9.7 Hz, 1H), 7.79 (d, J = 1.5 Hz, 1H), 7.69 (td, J = 1.5, 7.5
Hz, 1H), 7.51 (d, J = 9.7 Hz, 1H), 7.48 – 7.42 (m, 1H),
7.42 – 7.38 (m, 1H), 3.98 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ (ppm) 155.7, 150.3, 146.9, 134.1, 133.9, 130.3,
129.4, 128.5, 128.3, 123.9, 117.1, 111.3, 57.7. Elemental
analysis: calcd (%) for C13H9ClN2O2 (260.68): C 59.90, H
3.48; found: C 60.12, H 3.27.
1
as a yellow solid (MP = 156-159 ºC). H NMR (300 MHz,
CDCl3) δ (ppm) 8.53 (s, 4H), 8.02 (s, 2H), 7.86 (s, 2H).
13C NMR (100 MHz, CDCl3) δ (ppm) 148.6, 136.5, 132.7
(q, J = 33.6 Hz), 129.6, 128.4 (d, J = 2.6 Hz), 127.7, 123.2
(m), 123.1 (q, J = 270.1 Hz). Elemental analysis: calcd
(%) for C22H8F12N2O (544.30): C 48.55, H 1.48; found: C
48.62, H 1.54.
6-Methoxy-4-(2-
nitrophenyl)benzo[c][1,2,5]oxadiazole (22a): Following
the general procedure A using 2-bromonitrobenzene (191
mg, 1 mmol) and 6-methoxybenzofurazan (173 mg, 1.15
mmol), the residue was purified by flash chromatography
on silica gel (pentane-Et2O, 60-40) to afford the desired
compound 22a (103 mg, 38%) as a yellow solid (MP =
200-202 ºC). 1H NMR (400 MHz, CDCl3) δ (ppm) 8.20 (d,
J = 8.1 Hz, 1H), 7.77 (t, J = 7.6 Hz, 1H), 7.68 (t, J = 7.9
Hz, 1H), 7.59 (d, J = 7.6 Hz, 1H), 7.10 (d, J = 2.0 Hz, 1H),
6.92 (d, J = 2.0 Hz, 1H), 3.99 (s, 3H). 13C NMR (100
MHz, CDCl3) δ (ppm) 161.4, 150.1, 146.6, 133.5, 132.0,
130.3, 130.2, 128.8, 127.2, 125.2, 89.6, 56.2. Elemental
analysis: calcd (%) for C13H9N3O4 (271.23): C 57.57, H
3.34; found: C 57.21, H 3.56. 22b 1H NMR (400 MHz,
CDCl3) δ (ppm) 8.10 (d, J = 8.1 Hz, 1H), 7.95 (d, J = 9.7
Hz, 1H), 7.75 (t, J = 7.5 Hz, 1H), 7.70 (d, J = 7.5 Hz, 1H),
7.61 (t, J = 7.7 Hz, 1H), 7.46 (d, J = 9.7 Hz, 1H), 3.90 (s,
3H).
4,7-Bis(6-(trifluoromethyl)pyridin-2-
yl)benzo[c][1,2,5]oxadiazole (26): Following the general
procedure B using 2-bromo-6-(trifluoromethyl)pyridine
(678 mg, 3 mmol) and benzofurazan (120 mg, 1 mmol),
the residue was purified by flash chromatography on silica
gel (pentane-toluene, 80-20) to afford the desired
compound 26 (263 mg, 64%) as a yellow solid (MP = 209-
211 ºC). 1H NMR (300 MHz, CDCl3) δ (ppm) 8.96 (d, J =
8.0 Hz, 2H), 8.84 (s, 2H), 8.14 (d, J = 8.0 Hz, 2H), 7.78 (d,
J = 8.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm)
150.7, 147.5, 147.4 (q, J = 34.9 Hz), 137.8, 130.8, 126.2,
126.0, 120.3 (q, J = 275.7 Hz), 119.2.Elemental analysis:
calcd (%) for C18H8F6N4O (410.28): C 52.70, H 1.97;
found: C 52.89, H 1.63.
Procedure
B
(Palladium-catalyzed one-pot direct
Procedure
C
(acid-promoted the formation of
C4,C7-diarylation): To a 5 mL oven dried Schlenk tube,
benzofurazan derivative (1 mmol), aryl bromide (3 mmol),
AcOK (294 mg, 3 mmol), DMA (4 mL) and Pd(OAc)2 (2.2
mg, 0.01 mmol, 2 mol%) were successively added. The
reaction mixture was evacuated by vacuum-argon cycles (5
times) and stirred at 150 °C (oil bath temperature) for 16
hours. After cooling the reaction at room temperature and
concentration, the crude mixture was purified by silica
column chromatography to afford the desired diarylated
products.
quinoxalines): To a 5 mL oven dried Schlenk tube,
arylated benzofurazan derivative (0.5 mmol), p-
toluenesulfonic acid (8.6 mg, 0.05 mmol), 2-aminoethan-1-
ol (0.45 mL, 7.5 mmol) were successively added. The
reaction mixture wasstirred at 150 °C (oil bath
temperature) for 72 hours. After cooling the reaction at
room temperature and concentration, the crude mixture
was purified by silica column chromatography to afford
the desired arylated products.
5-(4-Chlorophenyl)quinoxaline (27): Following the
4,7-Diphenylbenzo[c][1,2,5]oxadiazole
(23):
general
procedure
C
using
4-(4-
Following the general procedure B using 1-bromobenzene
(471 mg, 3 mmol) and benzofurazan (120 mg, 1 mmol),
the residue was purified by flash chromatography on silica
gel (pentane-Et2O, 95-5) to afford the desired compound
23 (155 mg, 57%) as a yellow solid (MP = 190-191 ºC). 1H
NMR (400 MHz, CDCl3) δ (ppm) 8.11 – 8.03 (m, 4H),
chlorophenyl)benzo[c][1,2,5]oxadiazole (6) (115 mg, 0.5
mmol), the residue was purified by flash chromatography
on silica gel (pentane-CH2Cl2, 70-30) to afford the desired
compound 27 (101 mg, 84%) as a brown solid (MP = 109-
1
111 ºC). H NMR (400 MHz, CDCl3) δ (ppm) 8.97 – 8.85
(m, 2H), 8.20 (dd, J = 1.6, 8.3 Hz, 1H), 7.88 (t, J = 7.1 Hz,
1H), 7.82 (dd, J = 1.6, 7.2 Hz, 1H), 7.63 (d, J = 8.5 Hz,
2H), 7.51 (d, J = 8.5 Hz, 2H). 13C NMR (100 MHz,
CDCl3) δ (ppm) 144.9, 144.7, 143.1, 140.9, 140.0, 136.5,
134.1, 131.9, 130.5, 129.9, 129.3, 128.4. Elemental
analysis: calcd (%) for C14H9ClN2 (240.69): C 69.86, H
3.77; found: C 69.90, H 4.02.
7.71 (s, 2H), 7.62 – 7.54 (m, 4H), 7.53 – 7.47 (m, 2H). 13
C
NMR (100 MHz, CDCl3) δ (ppm) 149.3, 135.3, 129.2,
129.0, 128.9, 128.7, 128.4. Elemental analysis: calcd (%)
for C18H12N2O (272.31): C 79.39, H 4.44; found: C 79.57,
H 4.60.
4,7-Bis(4-chlorophenyl)benzo[c][1,2,5]oxadiazole
(24): Following the general procedure B using 1-bromo-4-
chlorobenzene (574 mg, 3 mmol) and benzofurazan (120
5-(Naphthalen-1-yl)quinoxaline (28): Following the
general
procedure
C
using
4-(naphthalen-1-
mg,
1
mmol), the residue was purified by flash
yl)benzo[c][1,2,5]oxadiazole (15) (123 mg, 0.5 mmol), the
residue was purified by flash chromatography on silica gel
(pentane-CH2Cl2, 70-30) to afford the desired compound
28 (111 mg, 87%) as a brown solid (MP = 100-103 ºC). 1H
NMR (400 MHz, CDCl3) δ (ppm) 8.88 (d, J = 1.8 Hz, 1H),
chromatography on silica gel (pentane-CH2Cl2, 80-20) to
afford the desired compound 24 (205 mg, 60%) as a yellow
solid (MP = 230-232 ºC). 1H NMR (400 MHz, CDCl3) δ
7
This article is protected by copyright. All rights reserved.

10.1002/adsc.201700435
Advanced Synthesis & Catalysis
8.77 (d, J = 1.8 Hz, 1H), 8.28 (dd, J = 1.5, 8.4 Hz, 1H),
8.01 – 7.91 (m, 3H), 7.86 (dd, J = 1.5, 7.1 Hz, 1H), 7.63
(dd, J = 7.0, 8.2 Hz, 1H), 7.53 (dd, J = 1.3, 7.0 Hz, 1H),
7.49 (ddd, J = 2.0, 6.0, 8.1 Hz, 1H), 7.38 – 7.30 (m, 2H).
13C NMR (100 MHz, CDCl3) δ (ppm) 144.9, 142.9, 142.3,
140.5, 136.5, 133.5, 132.7, 132.0, 129.7, 129.4, 128.5,
128.3, 128.1, 126.3, 125.9, 125.7, 125.2. Elemental
analysis: calcd (%) for C18H12N2 (256.31): C 84.35, H
4.72; found: C 84.14, H 4.96.
[8] H. Langhals, P. Knochel, A. Walter, S. Zimdars,
Synthesis 2012, 44, 3465-3477.
[9] N. Nakamura, Y. Tajima, K. Sakai, Heterocycles 1982,
17, 235-245.
[10] a) A. Ohta, Y. Akita, T. Ohkuwa, M. Chiba, R.
Fukunaga, A. Miyafuji, T. Nakata, N. Tani, Y. Aoyagi,
Heterocycles 1990, 31, 1951-1958; b) Y. Aoyagi, A.
Inoue, I. Koizumi, R. Hashimoto, K. Tokunaga, K.
Gohma, J. Komatsu, K. Sekine, A. Miyafuji, J. Kunoh,
Heterocycles 1992, 33, 257-272.
5,8-Bis(3,5-bis(trifluoromethyl)phenyl)quinoxaline
(29): Following the general procedure C using 4,7-bis(3,5-
bis(trifluoromethyl)phenyl)benzo[c][1,2,5] oxadiazole (25)
(272 mg, 0.5 mmol), the residue was purified by flash
chromatography on silica gel (pentane-CH2Cl2, 80-20) to
afford the desired compound 29 (227 mg, 82%) as a brown
[11] a) F. Kakiuchi, T. Kochi, Synthesis 2008, 3013-3039;
b) L. Ackermann, R. Vicente, A. R. Kapdi, Angew.
Chem. Int. Ed. 2009, 48, 9792-9826; c) F. Bellina, R.
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1
solid (MP = 200-203 ºC). H NMR (400 MHz, CDCl3) δ
(ppm) 8.98 (s, 2H), 8.30 – 8.16 (m, 4H), 8.01 (s, 2H), 8.00
(s, 2H). 13C NMR (100 MHz, CDCl3) δ (ppm) 145.3,
140.7, 139.6, 138.9, 131.5 (q, J = 33.7 Hz), 130.8, 130.3,
123.4 (q, J = 273.4 Hz), 121.8. Elemental analysis: calcd
(%) for C24H10F12N2 (554.34): C 52.00, H 1.82; found: C
52.18, H 2.07.
Acknowledgements
We thank the Algeria “Ministry of Higher Education and
Scientific Research” for a fellowship to I.I. We thank CNRS and
“Rennes Metropole” for providing financial support.
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Palladium-Catalyzed Regioselective Direct
Arylation of Benzofurazans at C4 Position
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