A highly efficient one-pot reaction of 2-(gem-dibromovinyl) phenols(thiophenols) with K4Fe(CN)6 to 2-cyanobenzofurans(thiophenes)

Article abstract of DOI:10.1039/c2ob25356a

2-Cyanobenzofurans and 2-cyanobenzothiophenes were prepared through an efficient one-pot Ullmann-reaction/cyanation reaction. In the presence of CuI/Na₂CO₃-Pd(OAc)₂/PPh₃ in DMF, the reaction of 2-(gem-dibromovinyl)phenols and 2-(gem-dibromovinyl)thiophenols with K₄Fe(CN)₆, as non-toxic and user-friendly cyanating reagent, proceeded smoothly to generate the corresponding 2-cyanobenzofurans and 2-cyanobenzothiophenes in good yields.

Full text of DOI:10.1039/c2ob25356a

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PAPER
A highly efficient one-pot reaction of 2-(gem-dibromovinyl)phenols-
(thiophenols) with K4Fe(CN)6 to 2-cyanobenzofurans(thiophenes)†
Wei Zhou,a Wei Chena and Lei Wang*a,b
Received 20th February 2012, Accepted 3rd April 2012
DOI: 10.1039/c2ob25356a
2-Cyanobenzofurans and 2-cyanobenzothiophenes were prepared through an efficient one-pot Ullmann-
reaction/cyanation reaction. In the presence of CuI/Na2CO3–Pd(OAc)2/PPh3 in DMF, the reaction of
2-(gem-dibromovinyl)phenols and 2-(gem-dibromovinyl)thiophenols with K4Fe(CN)6, as non-toxic and
user-friendly cyanating reagent, proceeded smoothly to generate the corresponding 2-cyanobenzofurans
and 2-cyanobenzothiophenes in good yields.
Representative methods for the preparation of heteroaromatic
Introduction
cyanides via the direct cyanation of heterocycles can be achieved
from the corresponding heterocycles with a suitable cyanide
agent. Methods for direct cyanation of pyridines,13a thiophe-
nols,13b,d indoles,13b,d,g pyrroles,13b,d and 2-phenylpyridines13c,e,f
have been reported in the literature. Most recently, the direct cya-
nation of 3-position of indoles and pyrroles,14a–d and 2-position
of benzoxazoles, benzothiazoles, benzimidazoles, caffeines, and
triazoles have been developed.14e However, the direct cyanation
of benzofurans and benzothiophenes for the synthesis of 2-cya-
nobenzofurans and 2-cyanobenzothiophenes has not been
described yet, to our knowledge because introduction of a cyano
functionality into a benzofuran or benzothiophene ring is more
difficult by using such an approach.
Over the past decade, gem-dihaloolefins have been received
much attention owing to their high reactivity and easy prep-
aration from the corresponding aldehydes.15 Most importantly,
2-(gem-dibromovinyl)phenols, 2-(gem-dibromovinyl)thiophe-
nols and 2-(gem-dibromovinyl)anilines were extensively used
for the preparation of a variety of heterocycles, such as
indoles,16 benzothiophenes,17 and benzofurans16d,i,17b via tran-
sition-metal-catalyzed one-pot Ullmann-type reaction/amin-
ation–Suzuki/Heck/Sonogashira coupling reactions with
organoboron agents,16a,i,17a alkenes,16c or alkynes.16d Recently,
Lautens et al. isolated 2-bromobenzofurans, 2-bromobenzothio-
phenes and 2-bromoindoles, as significant synthetic intermedi-
ates, which subsequently were used as electrophiles for further
carbon–carbon bond formations via transition-metal-catalyzed
cross-coupling reactions, from corresponding 2-(gem-dibromo-
vinyl)phenols, 2-(gem-dibromovinyl)thiophenols17b and 2-(gem-
dibromovinyl)anilines,18 respectively via Cu- and Pd-catalyzed
intramolecular cross-coupling reactions. Therefore, to expand the
application scope of gem-dibromoolefins and provide a practical
straightforward route to 2-substituted benzofused heterocycles is
more and more essential.
Heteroaromatic cyanides, are not only structural skeletons that
were widely found in dyes, agrochemicals, pharmaceutically
active compounds, materials and natural products,1 but also ver-
satile building blocks in modern organic chemistry.2 In addition,
they are readily converted to a variety of other organic com-
pounds, such as acids, esters, amides, amines, and aldehydes.3
Therefore, it is important to develop efficient methods to intro-
duce the cyano group into heteroaromatic compounds.
For the preparation of heteroaromatic cyanides, the traditional
methods are Rosenmund–von Braun method,4 and Sandmeyer
reaction.5 However, these reactions require a stoichiometric
amount of CuCN and suffer from harsh reaction conditions and
complicated workup procedures. Recently, transition-metal-cata-
lyzed cyanation of aromatic and heteroaromatic halides with
metal cyanides has received much attention.6 In general, nucleo-
philic metal-catalyzed cyanations proceed in the presence of Cu,
Pd, or Ni-complexes and various cyanation reagents, such as
KCN and NaCN‡,7 Zn(CN)2,8 CuCN,9 (CH3)2C(OH)CN,10
TMSCN,11 and K4Fe(CN)6.12 Compared with other cyanation
reagents, K4Fe(CN)6 exhibits excellent properties of low-cost,
non-toxic and handling without special precautions.
aDepartment of Chemistry, Huaibei Normal University, Huaibei, Anhui
235000, P R China. E-mail: leiwang@chnu.edu.cn; Fax: +86-561-309-
0518; Tel: +86-561-380-2069
bState Key Laboratory of Organometallic Chemistry, Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences, Shanghai 200032,
P R China
‡KCN and NaCN are extremely toxic [LDL0 (oral, human): 2.86 and
2.80 mg kg−1, respectively] and develop HCN on contact with acidic
water. K4[Fe(CN)6] is nontoxic and is used in the food industry for
metal precipitation in wine, it has also been used as an anti-agglutinating
auxiliary for NaCl. It is soluble in water without decomposition.
†Electronic supplementary information (ESI) available. See DOI:
10.1039/c2ob25356a
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Table 1 Optimization of the reaction conditionsa
Entry
Base
Pd catal./ligand
Solvent
2ab (%)
Scheme 1 One-pot reaction of 2-(gem-dibromovinyl)phenols(thiophe-
nols) with K4Fe(CN)6.
1
2
3
4
5
6
7
8
Na2CO3
t-BuOK
NaHCO3
t-BuONa
K2CO3
Et3N
Cs2CO3
K3PO4
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
PdCl2/PPh3
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
NMP
DMA
Glyme
DMSO
Toluene
THF
Dioxane
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
DMF
92
86
84
68
62
59
NR
NR
NR
NR
76
69
54
26
NR
NR
NR
85
78
69
In continuation of our efforts on the organic transformations
of gem-dihaloolefins,19 herein we report a novel one-pot reaction
of 2-(gem-dibromovinyl)phenols and 2-(gem-dibromovinyl)thio-
phenols with K4Fe(CN)6 in the presence of CuI/Na2CO3–Pd
(OAc)2/PPh3 in DMF. The reactions proceeded smoothly
through a one-pot Ullmann-reaction/cyanation process and gen-
erated the corresponding 2-cyanobenzofurans and 2-cyanoben-
zothiophenes in good yields under mild and low-toxic reaction
conditions (Scheme 1).
9
DMAP
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
29
30
31
DABCO
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Na2CO3
Results and discussion
Pd(PPh3)4
Our initial investigation was focused on the optimization of reac-
tion conditions for the model reaction of 2-(gem-dibromovinyl)
phenol (1a) with K4Fe(CN)6. As listed in Table 1, the base plays
an important role in the one-pot reaction. Among the bases
tested, Na2CO3 was the most suitable base. t-BuOK, NaHCO3,
t-BuONa, K2CO3, and Et3N were subsequently inferior.
However, no desired product 2a was isolated and only the inter-
mediate bromobenzofuran was formed when Cs2CO3, K3PO4,
DMAP, or DABCO was used as base instead of Na2CO3 in the
model reaction (Table 1, entries 1–10). The solvent also has a
significant effect on the model reaction. When the reaction was
carried out in the presence of CuI–Pd(OAc)2/PPh3 in DMF, 92%
yield of 2a was obtained, and 26–76% yields of 2a was isolated
when the reaction was performed in NMP, DMA, glyme, or
DMSO. Unfortunately, no desired 2a was detected and only bro-
mobenzofuran was obtained as the reaction media was switched
to toluene, THF or dioxane (Table 1, entries 11–17). For the
effect of palladium catalyst on the model reaction, the one-pot
reaction could occur in the presence of a catalytic amount
(1.0 mol%) of palladium salt/P-ligand or palladium complex,
such as Pd(OAc)2/PPh3, PdCl2/PPh3, Pd(PPh3)4, Pd(PPh3)2Cl2,
PdCl2(CH3CN)2, Pd(OAc)2/PCy3, Pd(OAc)2/dppf, or Pd(OAc)2/
dppe in DMF in the presence of CuI and Na2CO3, 2a was
obtained in 69–92% yields (Table 1, entries 1 and 18–24). To
our delight, 92% yield of 2a was isolated, representing the best
results, when Pd(OAc)2/PPh3 or Pd(OAc)2/dppf was used as cat-
alyst system in the model reaction (Table 1, entries 1 and 23). It
is obvious that palladium, as well as P-ligand are essential in the
reaction (Table 1, entries 25 and 26). For the optimiztion of CN
source, K4Fe(CN)6 displayed the highest reactivity in the reac-
tion. Other CN sources, such as CuCN, K3FeCN6 and TMSCN
exhitited the low reactivity to the reaction. Although NaCN dis-
played the comparable reactivity with K4Fe(CN)6, but it is a very
toxic compound (Table 1, entries 27–30). However, the use of a
single metal CuI or Pd(OAc)2 for the one-pot reaction was not
effective, even in the presence of Pt-Bu3 (Table 1, entries 26 and
31).18 For the further optimization of reaction conditions, the
Pd(PPh3)2Cl2
PdCl2(CH3CN)2
Pd(OAc)2/PCy3
Pd(OAc)2/dppf
Pd(OAc)2/dppe
Pd(OAc)2
82
84
92
86
25
PPh3
NR
42c
27d
0e
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/PPh3
Pd(OAc)2/Pt-Bu3
92f
38g
a Reaction conditions: 1a (1.0 mmol), CuI (0.10 mmol), base
(2.0 mmol), solvent (2.0 mL) at 80 °C, 6 h; then K4Fe(CN)6
(0.20 mmol), Pd catal. (0.01 mol), ligand (0.02 mmol) at 120 °C, 6 h.
b Isolated yields. c K3FeCN6 (0.20 mmol). d CuCN (1.20 mmol).
e TMSCN (1.20 mmol). f NaCN (1.20 mmol). g In the absence of CuI.
sequential reaction of 2-(gem-dibromovinyl)phenol in the pres-
ence of CuI (10 mol%), Na2CO3 (2.0 equiv) in DMF at 80 °C
for 6 h, then K4Fe(CN)6 (0.20 mmol) and Pd(OAc)2/PPh3
(1.0 mol%) were added to the reaction system and then the cya-
nation reaction was carried out at 120 °C for 6 h.
Under the optimized reaction conditions, the scope of substi-
tuted 2-(gem-dibromovinyl)phenols and 2-(gem-dibromovinyl)
thiophenols with K4Fe(CN)6 in the one-pot Ullmann-reaction/
cyanation reaction was investigated. The results are shown in
Scheme 2. As can be seen from Scheme 2, the one-pot reactions
of K4Fe(CN)6 with substituted 2-(gem-dibromovinyl)phenols
(Scheme 2, 1a–o) generated the corresponding products (2a–o)
in good to excellent yields. A variety of 2-(gem-dibromovinyl)-
phenols bearing substituents on the benzene rings were exam-
ined. The results in Scheme 2 indicated that a variety of func-
tional groups, including electron-donating and electron-
withdrawing ones were tolerated. 2-(gem-Dibromovinyl)phenols
with an electron-donating group, such as Me, MeO, t-Bu, and a
weak electron-withdrawing group, such as Cl, on the para-pos-
ition of phenols, gave superior yields of the products (2b–e) to
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Scheme 3 The one-pot reaction of 1s and the further transformation of
2s and 2a.
Scheme 2 Cu/Pd-catalyzed one-pot reactions of 2-(gem-dibromovinyl)-
a
phenols(thiophenols) with K4Fe(CN)6
.
that of 2f, with a strong electron-withdrawing group, NO2 on the
para-position of phenols. It should be noted that 2-(gem-dibro-
movinyl)phenol with a strong electron-donating functionality,
such as MeO on the meta-position of phenol generated 76%
yield of the product 2g. Meanwhile, the ortho-effect is not
obvious for Me, MeO, and Ph groups on the ortho-position of
phenols in the reactions (2h, 2j and 2k). However, a little ortho-
effect was observed for relatively larger bulky groups, such as
EtO and t-Bu groups (2i and 2l). Disubstituted 2-(gem-dibromo-
vinyl)phenols, such as 1m, 1n, and 1o, also underwent the one-
pot reaction smoothly with K4Fe(CN)6 under the present reaction
conditions and afforded the corresponding products 2m–o in
75–85% yields. Under the recommended reaction conditions, 1-
(gem-dibromovinyl)-2-naphthalenol also underwent the reaction
to generate the corresponding product 2p in 77% yield. The
present reaction conditions were also suitable for the synthesis of
2-cyanobenzothiophenes (2q and 2r) from the corresponding 2-
(gem-dibromovinyl)thiophenols (1q and 1r) and K4Fe(CN)6 in
one-pot.
Scheme 4 Possible reaction mechanism.
cyanobenzofuran 2s was obtained in 57% yield (Scheme 3). On
the other hand, when the reaction of 1s and K4Fe(CN)6 with
2.5 : 1 molar ratio was performed under the reaction conditions
(b), an Ullmann-type di-cyanation product, 2,5-dicyanobenzo-
furan 2t was isolated in 76% yield (Scheme 3). These results
indicated that the reactivity of Br at furan ring is more than that
of Br in benzene ring of 2,5-dibromobenzofuran. When obtained
2s was used as a starting material to react with 4-methoxyphe-
nylboronic acid under the classic Suzuki reaction conditions, the
corresponding Suzuki coupling product, 2-cyano-5-(4-methoxy-
phenyl)benzofuran (2u) was isolated in 92% yield. We also used
2a as a starting material to react with 2-aminophenylthionol in
the presence of phosphotungstic acid, and the di-heterocycle
compound, 2-(benzofuran-2-yl)benzothiazole (2v) was obtained
in 91% yield (Scheme 3).
When the reaction of 4-bromo-2-(gem-dibromovinyl)phenol
(1s) and K4Fe(CN)6 with 5 : 1 molar ratio was performed under
reaction conditions (a), a mono-cyanation product, 5-bromo-2-
Although the exact mechanism of this reaction is not clear, a
possible pathway was proposed and shown in Scheme 4. The
reaction occurs involving an intramolecualr Ullmann-type
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under a nitrogen atmosphere. 1H and 13C NMR spectra
were measured on a Bruker Avance 400 MHz NMR spec-
trometer with CDCl3 as solvent and recorded in ppm relative to
internal tetramethylsilane standard. High resolution mass spec-
troscopy data of the product were collected on a Waters Micro-
mass GCT instrument. Solvents, and general chemicals were
purchased from commercial suppliers and used without further
purification. All the gem-dibromovinyl substrates were syn-
thesized according to the reported procedures in the
literatures.17b,22
Scheme 5 The formation of 2-bromobenzofuran and D-labelled
experiment.
Typical procedure for the one-pot reaction
A sealable reaction tube equipped with a magnetic stirrer bar
was charged with gem-dibromovinyl substrate (1.0 mmol), CuI
(0.10 mmol), Na2CO3 (2.0 mmol) and DMF (2.0 mL). The
rubber septum was then replaced by a Teflon-coated screw cap,
and the reaction vessel placed in an oil bath at 80 °C. After stir-
ring of the mixture at this temperature for 6 h, it was cooled to
room temperature and K4Fe(CN)6 (0.20 mmol), Pd(OAc)2
(0.01 mmol) and PPh3 (0.02 mmol) were added to the reaction
system. Then the reaction vessel was placed in an oil bath at
120 °C for 6 h. It was cooled to room temperature after the reac-
tion and diluted with ethyl acetate, washed with water and brine,
dried with Mg2SO4. After the solvent was removed under
reduced pressure, the residue was purified by column chromato-
graphy on silica gel (eluant: petroleum ether) to afford the corre-
sponding product.
reaction of 2-(gem-dibromovinyl)phenol, and subsequently inter-
molecular cyanation reaction with K4Fe(CN)6. Initially, an elim-
ination of HBr from 2-(gem-dibromovinyl)phenol (1a) via a
classic Ullmann reaction to 2-bromobenzofuran taken place in
the presence of CuI and Na2CO3.20 The obtained 2-bromobenzo-
furan then underwent an oxidative addition with Pd(0) from the
reduction of its precursor Pd(OAc)2 in the presence of a reducing
agent, such as PPh3,21 to generate intermediate B. The obtained
B proceeded in a ligand exchange with CN− to generate an Ar–
Pd(II)–CN intermediate C, which subsequently underwent reduc-
tive elimination to form the corresponding product 2-cyanoben-
zofuran, 2a, along with the generation of Pd(0), and finally the
catalytic cycle was closed.
To verify the formation of 2-bromobenzofuran, 1a was carried
out in the presence of CuI (10 mol%) and Na2CO3 (2.0 equiv) in
DMF and 2-bromobenzofuran was isolated in 94% yield. The
obtained 2-bromobenzofuran then reacted with K4Fe(CN)6 in the
presence of Pd(OAc)2/PPh3 to give 2a in 95% yield (Scheme 5,
eqn (1)). We also tried the reaction of 1-bromo-2-phenylacety-
lene with K4Fe(CN)6 under the present reaction conditions.
However, no cyanation product was obtained, and a homo-coup-
ling product was obtained in 92% yield (Scheme 5, eqn (2)).
When 2-(gem-dibromovinyl)phenol-D, prepared from D2O
exchange, was carried out in the presence of CuI/Na2CO3, 2-bro-
mobenzofuran was isolated in 93% yield without a D-rich
element in the product (Scheme 5, eqn (3)). These results
support the intermolecular reaction of 1a through a key inter-
mediate A.
Benzofuran-2-carbonitrile, 2a. White solid, m.p. 36–38 °C.
1H NMR (400 MHz, CDCl3): δ 7.69 (d, J = 8.0 Hz, 1H),
7.57–7.50 (m, 2H), 7.46 (s, 1H), 7.40–7.36 (m, 1H); 13C NMR
(100 MHz, CDCl3): δ 155.59, 128.36, 127.22, 125.42, 124.48,
122.50, 118.37, 111.98, 111.74. IR (KBr, cm−1): 2230 (νCuN).
HRMS (EI) ([M]+) Calcd for C9H5NO: 143.0371, Found:
143.0372.
Conclusion
5-Methylbenzofuran-2-carbonitrile, 2b. White solid, m.p.
71–73 °C. H NMR (400 MHz, CDCl3): δ 7.43–7.41 (m, 2H),
In conclusion, a novel and highly efficient synthetic method for
the preparation of 2-cyanobenzofurans and 2-cyanobenzothio-
phenes has been developed. In the presence of CuI/Na2CO3–Pd
(OAc)2/PPh3, 2-(gem-dibromovinyl)phenols and 2-(gem-dibro-
movinyl)thiophenols reacted with K4Fe(CN)6 smoothly to gener-
ated the corresponding products in good yields through an
Ullmann reaction/cyanation reaction in one-pot. The extend
investigation of this kind reaction and detail reaction mechanism
are currently underway in our laboratory.
1
7.36 (s, 1H), 7.32–7.30 (m, 1H), 2.46 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 154.19, 134.27, 129.92, 127.24, 125.58,
121.96, 118.16, 111.92, 111.51, 21.19. IR (KBr, cm−1): 2225
(νCuN). HRMS (EI) ([M]+) Calcd for C10H7NO: 157.0528,
Found: 157.0530.
Experimental section
All the reactions of 2-(gem-dibromovinyl)phenols and 2-(gem-
dibromovinyl)thiophenols with K4Fe(CN)6 were carried out
5-(tert-Butyl)benzofuran-2-carbonitrile, 2c. White solid, m.p.
58–60 °C. H NMR (400 MHz, CDCl3): δ 7.64 (d, J = 2.0 Hz,
1
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1H), 7.59–7.57 (m, 1H), 7.47 (d, J = 8.8 Hz, 1H), 7.41 (s, 1H),
1.38 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 154.05, 147.88,
127.28, 126.76, 125.27, 118.67, 118.36, 111.99, 111.40, 34.85,
31.60. IR (KBr, cm−1): 2225 (νCuN). HRMS (EI) ([M]+) Calcd
for C13H13NO: 199.0997, Found: 199.0995.
1H), 7.43 (s, 1H), 7.30–7.23 (m, 2H), 2.53 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 154.92, 129.05, 126.97, 125.02, 124.61,
122.53, 119.87, 118.69, 111.98, 14.82. IR (KBr, cm−1): 2229
(νCuN). HRMS (EI) ([M]+) Calcd for C10H7NO: 157.0528,
Found: 157.0525.
5-Methoxybenzofuran-2-carbonitrile, 2d. White solid, m.p.
1
89–91 °C. H NMR (400 MHz, CDCl3): δ 7.43 (d, J = 9.2 Hz,
1H), 7.37 (s, 1H), 7.12–7.09 (m, 1H), 7.05 (d, J = 2.8 Hz, 1H),
3.85 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 157.07, 150.77,
127.74, 126.05, 118.38, 118.35, 112.64, 111.82, 103.31, 55.83.
IR (KBr, cm−1): 2230 (νCuN). HRMS (EI) ([M]+) Calcd for
C10H7NO2: 173.0477, Found: 173.0474.
7-(tert-Butyl)benzofuran-2-carbonitrile, 2i. White solid, m.p.
101–103 °C. 1H NMR (400 MHz, CDCl3): δ 7.53–7.51 (m, 1H),
7.45 (s, 1H), 7.41–7.39 (m, 1H), 7.30–7.26 (m, 1H), 1.50 (s,
9H); 13C NMR (100 MHz, CDCl3): δ 154.24, 135.96, 126.47,
126.11, 124.98, 124.61, 120.36, 118.47, 112.16, 34.43, 29.68.
IR (KBr, cm−1): 2227 (νCuN). HRMS (EI) ([M]+) Calcd for
C13H13NO: 199.0997, Found: 199.0995.
5-Chlorobenzofuran-2-carbonitrile, 2e. White solid, m.p.
1
123–125 °C. H NMR (400 MHz, CDCl3): δ 7.66 (dd, J = 2.0,
0.8 Hz, 1H), 7.51–7.45 (m, 2H), 7.40 (d, J = 0.8 Hz, 1H); 13C
NMR (100 MHz, CDCl3): δ 153.96, 130.44, 128.85, 128.68,
126.77, 121.97, 117.68, 113.17, 111.22. IR (KBr, cm−1): 2229
(νCuN). HRMS (EI) ([M]+) Calcd for C9H4NOCl: 176.9981,
Found: 176.9980.
7-Phenylbenzofuran-2-carbonitrile, 2j. White solid, m.p.
116–118 °C. 1H NMR (400 MHz, CDCl3): δ 7.82–7.79 (m, 2H),
7.66–7.63 (m, 2H), 7.54–7.51 (m, 3H), 7.46–7.42 (m, 2H); 13C
NMR (100 MHz, CDCl3): δ 153.03, 134.93, 128.80, 128.52,
128.35, 127.72, 127.41, 126.51, 126.29, 125.13, 121.50, 118.62,
111.80. IR (KBr, cm−1): 2228 (νCuN). HRMS (EI) ([M]+) Calcd
for C15H9NO: 219.0684, Found: 219.0681.
5-Nitrobenzofuran-2-carbonitrile, 2f. White solid, m.p.
117–119 °C. 1H NMR (400 MHz, DMSO-d6): δ 8.82 (d, J = 2.4
Hz, 1H), 8.45–8.42 (m, 1H), 8.28 (d, J = 4.0 Hz, 1H), 8.02–7.99
(m, 1H); 13C NMR (100 MHz, DMSO-d6): δ 158.00, 145.30,
129.65, 126.43, 124.33, 121.21, 120.49, 113.71, 111.60. IR
(KBr, cm−1): 2237 (νCuN). HRMS (EI) ([M]+) Calcd for
C9H4N2O3: 188.0222, Found: 188.0223.
7-Methoxybenzofuran-2-carbonitrile, 2k. White solid, m.p.
102–104 °C. 1H NMR (400 MHz, CDCl3): δ 7.43 (s, 1H),
7.30–7.22 (m, 2H), 6.97 (dd, J = 7.6, 1.2 Hz, 1H), 4.02 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 145.65, 145.42, 127.39,
127.10, 125.35, 118.64, 114.23, 111.54, 109.74, 56.19. IR (KBr,
cm−1): 2228 (νCuN). HRMS (EI) ([M]+) Calcd for C10H7NO2:
173.0477, Found: 173.0476.
6-Methoxybenzofuran-2-carbonitrile, 2g. White solid, m.p.
1
78–80 °C. H NMR (400 MHz, CDCl3): δ 7.51 (d, J = 8.4 Hz,
1H), 7.38 (s, 1H), 7.01–6.97 (m, 2H), 3.87 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 161.20, 157.14, 126.30, 122.66, 118.61,
118.55, 114.88, 112.10, 95.44, 55.75. IR (KBr, cm−1): 2218
(νCuN). HRMS (EI) ([M]+) Calcd for C10H7NO2: 173.0477,
Found: 173.0475.
7-Ethoxybenzofuran-2-carbonitrile, 2l. White solid, m.p.
74–76 °C. 1H NMR (400 MHz, CDCl3): δ 7.43 (s, 1H),
7.27–7.20 (m, 2H), 6.96 (dd, J = 7.6, 1.6 Hz, 1H), 4.26 (q, J =
6.8 Hz, 2H), 1.52 (t, J = 7.2 Hz, 3H); 13C NMR (100 MHz,
CDCl3): δ 145.57, 144.96, 127.28, 127.14, 125.32, 118.69,
114.07, 111.62, 110.74, 64.78, 14.69. IR (KBr, cm−1): 2231
7-Methylbenzofuran-2-carbonitrile, 2h. White solid, m.p.
46–48 °C. H NMR (400 MHz, CDCl3): δ 7.49 (d, J = 7.2 Hz,
1
4176 | Org. Biomol. Chem., 2012, 10, 4172–4178
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Benzothiophene-2-carbonitrile, 2q. Colorless oil. 1H NMR
(400 MHz, CDCl3): δ 7.91–7.83 (m, 3H), 7.54–7.44 (m, 2H);
13C NMR (100 MHz, CDCl3): δ 141.21, 137.37, 134.90,
127.80, 125.66, 125.20, 122.29, 114.38, 109.59. IR (KBr,
cm−1): 2224 (νCN). HRMS (EI) ([M]+) Calcd for
C9H5NS:159.0143, Found: 159.0147.
(νCuN). HRMS (EI) ([M]+) Calcd for C11H9NO2: 187.0633,
Found: 187.0636.
5,7-Dimethylbenzofuran-2-carbonitrile, 2m. White solid, m.p.
1
88–90 °C. H NMR (400 MHz, CDCl3): δ 7.35 (s, 1H), 7.25 (d,
J = 2.4 Hz, 1H), 7.11 (s, 1H), 2.48 (s, 3H), 2.41 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 153.50, 134.31, 130.69, 126.94,
125.15, 121.88, 119.28, 118.42, 112.12, 21.17, 14.76. IR (KBr,
cm−1): 2230 (νCuN). HRMS (EI) ([M]+) Calcd for C11H9NO:
171.0684, Found: 171.0686.
4-Chlorobenzothiophene-2-carbonitrile, 2r. White solid, m.p.
107–109 °C. 1H NMR (400 MHz, CDCl3): δ 7.99 (s, 1H),
7.75–7.71 (m, 1H), 7.47–7.42 (m, 2H); 13C NMR (100 MHz,
CDCl3): δ 142.07, 135.99, 133.03, 130.24, 128.51, 125.58,
120.77, 113.75, 110.53. IR (KBr, cm−1): 2226 (νCuN). HRMS
(EI) ([M]+) Calcd for C9H4NSCl: 192.9753, Found: 192.9756.
6,7-Dimethylbenzofuran-2-carbonitrile, 2n. White solid, m.p.
1
37–39 °C. H NMR (400 MHz, CDCl3): δ 7.36 (d, J = 9.6 Hz,
5-Bromobenzofuran-2-carbonitrile, 2s. White solid, m.p.
147–149 °C. H NMR (400 MHz, CDCl3): δ 7.83 (d, J = 2.0
2H), 7.15 (d, J = 8.0 Hz, 1H), 2.43 (s, 3H), 2.41 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 155.42, 137.24, 126.90, 126.42,
122.86, 120.63, 118.87, 118.78, 112.23, 19.32, 11.50. IR (KBr,
cm−1): 2226 (νCuN). HRMS (EI) ([M]+) Calcd for C11H9NO:
171.0684, Found: 171.0680.
1
Hz, 1H), 7.61 (dd, J = 8.8, 2.0 Hz, 1H), 7.45 (d, J = 8.8 Hz,
1H), 7.40 (d, J = 0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ
154.31, 131.48, 128.48, 127.35, 125.07, 117.75, 117.50, 113.55,
111.15. IR (KBr, cm−1): 2228 (νCuN). HRMS (EI) ([M]+) Calcd
for C9H4NOBr: 220.9476, Found: 220.9474.
Benzofuran-2,5-dicarbonitrile,
2t. White
solid,
m.p.
5,7-Dichlorobenzofuran-2-carbonitrile, 2o. White solid, m.p.
1
171–173 °C. H NMR (400 MHz, CDCl3): δ 8.09 (d, J = 1.2
Hz, 1H), 7.80 (dd, J = 8.8, 1.6 Hz, 1H), 7.70 (d, J = 8.8 Hz,
1H), 7.56 (d, J = 0.8 Hz, 1H); 13C NMR (100 MHz, CDCl3): δ
156.77, 131.44, 129.62, 127.85, 126.12, 118.08, 117.84, 113.51,
110.59, 109.05. IR (KBr, cm−1): 2227 (νCuN), 2228 (νCuN).
HRMS (EI) ([M]+) Calcd for C10H4N2O: 168.0324, Found:
168.0320.
1
109–112 °C. H NMR (400 MHz, CDCl3): δ 7.58 (d, J = 2.0
Hz, 1H), 7.51 (d, J = 1.6 Hz, 1H), 7.45 (s, 1H); 13C NMR
(100 MHz, CDCl3): δ 150.10, 130.72, 129.40, 128.54, 127.66,
120.55, 118.47, 118.08, 110.58. IR (KBr, cm−1): 2234 (νCuN).
HRMS (EI) ([M]+) Calcd for C9H3NOCl2: 210.9592, Found:
210.9595.
5-(4-Methoxyphenyl)benzofuran-2-carbonitrile,
2u. White
Naphtho[2,1-b]furan-2-carbonitrile, 2p. White solid, m.p.
88–90 °C. H NMR (400 MHz, CDCl3): δ 8.05 (d, J = 7.6 Hz,
1
1
solid, m.p. 87–89 °C. H NMR (400 MHz, CDCl3): δ 7.77 (d,
J = 1.6 Hz, 1H), 7.69–7.67 (m, 1H), 7.58–7.47 (m, 4H),
7.02–6.98 (m, 2H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 159.34, 154.91, 138.03, 132.90, 128.41, 127.95, 127.73,
126.03, 120.09, 118.57, 114.37, 112.10, 111.78, 55.35. IR (KBr,
cm−1): 2226 (νCuN). HRMS (EI) ([M]+) Calcd for
C16H11NO2:249.0790, Found: 249.0788.
1H), 7.94 (d, J = 8.0 Hz, 1H), 7.87 (d, J = 9.2 Hz, 1H), 7.82 (d,
J = 0.8 Hz, 1H), 7.67–7.63 (m, 1H), 7.60–7.54 (m, 2H); 13C
NMR (100 MHz, CDCl3): δ 154.11, 130.57, 129.93, 128.98,
127.67, 127.22, 126.44, 125.87, 123.12, 121.36, 117.16, 112.03,
111.99. IR (KBr, cm−1): 2224 (νCuN). HRMS (EI) ([M]+) Calcd
for C13H7NO: 193.0528, Found: 193.0529.
This journal is © The Royal Society of Chemistry 2012
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2-(Benzofuran-2-yl)benzothiazole, 2v. Yellow solid,23 m.p.
218–220 °C. H NMR (400 MHz, CDCl3): δ 8.14 (d, J = 8.4
F. Y. Kwong, Org. Lett., 2011, 13, 648; (f) B. Mariampillai, J. Alliot,
M. Li and M. Lautens, J. Am. Chem. Soc., 2007, 129, 15372.
1
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Hz, 1H), 7.95 (d, J = 8.0 Hz, 1H), 7.70 (d, J = 7.6 Hz, 1H), 7.64
(d, J = 8.4 Hz, 1H), 7.56–6.53 (m, 2H), 7.46–6.41 (m, 2H),
7.34–7.41 (m, 1H); 13C NMR (100 MHz, CDCl3): δ 157.58,
155.51, 153.86, 149.79, 134.70, 128.15, 126.67, 126.45, 125.64,
123.78, 123.51, 122.12, 121.66, 111.87, 107.55.
Acknowledgements
This work was financially supported by the National Science
Foundation of China (nos. 21172092 and 20102039).
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