Synthesis of (Z)-3-aryloxy-acrylonitriles, (E)-3-aryloxy-acrylonitriles and 3-cyanobenzofurans through the sequential reactions of phenols with propiolonitriles

Article abstract of DOI:10.1039/c2ob25969a

A Na₂CO₃-promoted addition of phenols to propiolonitriles generated (Z)-3-aryloxy-acrylonitriles in nearly quantitative yields with exclusively Z-isomers, and a DABCO-promoted addition reaction of phenols with propiolonitriles afforded mainly (E)-3-aryloxy-acrylonitriles with high yields. The obtained (E)-3-aryloxy-acrylonitriles underwent intramolecular cyclization to give 3-cyanobenzofurans in good yields through palladium-catalyzed direct C-H bond functionalization.

Full text of DOI:10.1039/c2ob25969a

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PAPER
Synthesis of (Z)-3-aryloxy-acrylonitriles, (E)-3-aryloxy-acrylonitriles and
3-cyanobenzofurans through the sequential reactions of phenols with
propiolonitriles†
Wei Zhou,a Yicheng Zhang,a Pinhua Lia and Lei Wang*a,b
Received 19th May 2012, Accepted 3rd July 2012
DOI: 10.1039/c2ob25969a
A Na2CO3-promoted addition of phenols to propiolonitriles generated (Z)-3-aryloxy-acrylonitriles in
nearly quantitative yields with exclusively Z-isomers, and a DABCO-promoted addition reaction of
phenols with propiolonitriles afforded mainly (E)-3-aryloxy-acrylonitriles with high yields. The obtained
(E)-3-aryloxy-acrylonitriles underwent intramolecular cyclization to give 3-cyanobenzofurans in good
yields through palladium-catalyzed direct C–H bond functionalization.
Introduction
Aromatic nitriles, especially heteroaromatic cyanide units, are
important structural motifs frequently found in a variety of bio-
logically active compounds, agrochemicals, dyes, materials and
natural products.1 Moreover, they are also versatile building
Scheme 1 Synthesis of heteroaromatic cyanides.
blocks, as well as starting materials for the synthesis of a number
of their corresponding derivatives, such as acids, esters, amides,
amines, aldehydes, and so forth by modern organic synthesis2
C–H bonds of indoles,8 Cu-catalyzed cyanation of heterocycle
C–H bonds,9 and Cu-catalyzed cyanation of 2-arylpyridine and
indole C–H bonds (Scheme 1, eqn (3))10 have been reported in
the literature. Nevertheless, the requirement of the chelation
group in some cases would limit the substrate scope.
through simple and easy transformations.3
The classic synthetic protocols for the synthesis of hetero-
aromatic cyanides via cyanating reactions of heteroaromatic com-
pounds are the Rosenmund–von Braun method and the
Sandmeyer reaction.4 However, there are some drawbacks, such
as stoichiometric amount of cuprous cyanide required, harsh
reaction conditions used and laborious isolation of products
needed in the reactions. In recent years, transition-metal-cata-
lyzed cyanation of heteroaromatic halides with metal cyanides,
acetone cyanohydrin, TMSCN, and K4Fe(CN)6 (Scheme 1,
eqn (1)),5 and electrophilic cyanation of metalated hetero-
aromatics using cyano electrophiles (Scheme 1, eqn (2))6 have
attracted much attention. However, pre-functionalized substrates
are required.
However, compared to the direct cyanation of pyridines,11a
thiophenols,11b,d indole, substituted indoles, and pyrroles,8,11b–d
2-phenylpyridines,7,10 and benzoxazole, benzothiazole, benzimi-
dazole, caffeine, and triazoles,9 introduction of a cyano function-
ality into the 3-position of benzofuran ring, an electron-rich
heteroaromatic ring, is more difficult. When using transition-
metal-catalyzed cyanation of heteroaromatic halides (Scheme 1,
eqn (1)) or electrophilic cyanation of metalated heteroaromatics
(Scheme 1, eqn (2)), the requisite 3-halo benzofurans are not
easily prepared via the general halogenation of benzofurans.12 In
addition, the direct cyanation of benzofurans at the 3-position is
also rare.8a,13
Most recently, the direct cyanation of heteroarenes as well as
chelation-assisted reactions, such as Pd-catalyzed cyanation
of C–H bonds of 2-arylpyridines,7 Pd-catalyzed cyanation of
In our continuing efforts on organic transformations through
C–H functionalizations and preparation of heteroaromatic
cyanides,14 herein we report that a Na2CO3-promoted addition of
phenols to propiolonitriles generated (Z)-3-aryloxy-acrylonitriles
in nearly quantitative yields with exclusively Z-isomers, and a
DABCO-promoted addition reaction of phenols with propiolo-
nitriles afforded mainly (E)-3-aryloxy-acrylonitriles with high
yields. The obtained (E)-3-aryloxy-acrylonitriles underwent
intramolecular cyclization to afford the corresponding
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
†Electronic supplementary information (ESI) available. CCDC 879485
and 879486. For ESI and crystallographic data in CIF or other electronic
format see DOI: 10.1039/c2ob25969a
7184 | Org. Biomol. Chem., 2012, 10, 7184–7196
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Table 1 Optimization of the reaction conditions for the addition of 4-
methylphenol (1b) to 3-phenylpropiolonitrile (2a)a
Temp. Yieldb (3b + E : Z
Entry Base (equiv)
Solvent
(°C)
3b′) (%)
ratio
1
2
3
4
5
6
7
8
—
DMF
DMF
rt
rt
rt
rt
rt
rt
0
91
97
48
97
94
15
32
53
97
49
36
53
34
17
0/0
96
0 : 0
K2CO3 (1.0)
0 : 100
0 : 100
0 : 100
0 : 100
0 : 100
0 : 100
0 : 100
10 : 90
12 : 88
34 : 66
58 : 42
86 : 14
33 : 67
0 : 100
0 : 0
Na2CO3 (1.0) DMF
Na2CO3 (0.5) DMF
Na2CO3 (1.5) DMF
Na2CO3 (1.0) DMAc
Na2CO3 (1.0) (CH2Cl)2 rt
Na2CO3 (1.0) CH3CN rt
Na2CO3 (1.0) C2H5OH rt
Na2CO3 (1.0) DMF
DABCO (1.0) DMF
DABCO (1.0) CH2Cl2
DABCO (1.0) (CH2Cl)2 rt
DABCO (1.0) C2H5OH rt
Scheme 2 Synthesis of (Z)-3-aryloxy-acrylonitriles, (E)-3-aryloxy-
acrylonitriles and 3-cyanobenzofurans.
3-cyanobenzofurans in good yields through
a palladium-
catalyzed direct C–H bond functionalization (Scheme 2).
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
100
rt
rt
Results and discussion
Firstly, our exploration was focused on the optimization of reac-
tion conditions for the model addition of 4-methylphenol (1b) to
3-phenylpropiolonitrile (2a). Table 1 shows that the base plays
an important role in the reaction,15 and base is essential in the
model reaction (Table 1, entry 1). When 1 equiv of Na2CO3 or
K2CO3 was used as a base, the model reaction proceeded
smoothly in DMF at room temperature (25 °C) and generated the
corresponding addition product 3b + 3b′ in 97, or 91% yield,
with 100% Z-isomer 3b′ (Table 1, entries 2 and 3). On the other
hand, organic base DABCO (1,4-diazabicyclo[2.2.2]octane,
1 equiv) could promote the model reaction with increasing
product yield of 3b + 3b′ (up to 96%) and E-isomer (3b) ratio
(E : Z = 3b : 3b′ = 85 : 15) in ClCH2CH2Cl at 45 °C (Table 1,
entries 11–19). Fortunately, the mixture of a pair of Z- and
E-isomers could be separated and isolated by chromatography on
a silica column. However, only a trace amount of 3b + 3b′ was
isolated when Et3N, Ph3N, DBU (1,8-diazabicycloundec-7-ene),
or DMAP (4-dimethylaminopryidine) was used as a base in
ClCH2CH2Cl at 45 °C (Table 1, entries 20–23).
A variety of phenols and propiolonitriles were examined for
the extension of the addition reaction. As can be seen from
Table 2, when the reaction of various substituted phenols and
3-aryl(aliphatic)-propiolonitriles was performed under Na2CO3/
DMF/20–25 °C reaction conditions, the corresponding addition
products were isolated in almost quantitative yields with
Z-isomers as the sole ones (Table 2, entries 1–19). An obvious
ortho-position effect of 3-arylpropiolonitrile was observed
(Table 2, entry 20). Under DABCO/ClCH2CH2Cl/45 °C reaction
conditions, the phenols also exhibited high reactivity to 3-phenyl-
propiolonitrile and the corresponding addition products were
obtained in excellent yields with the ratios of E : Z in the range
of 93 : 7 to 74 : 26 (Table 2, entries 1′–13′). However, the E : Z
ratio of the product obtained using phenol with an electron-with-
drawing group at the para-position, was greater than that of the
phenol without substitution, or with an electron-donating group
(Table 2, entries 9′–11′ vs. 1′–8′, 12′, and 13′). The addition of
α-naphthalenol to 3-phenylpropiolonitrile generated 3n + 3n′ in
96% yield with 70 : 30 (E : Z) ratio (Table 2, entry 14′). The
DABCO (1.0) CH3CN
rt
DABCO (1.0) (CH2Br)2 rt
DABCO (1.0) (CH2Cl)2 45
DABCO (1.0) (CH2Cl)2 65
DABCO (0.5) (CH2Cl)2 45
Et3N (1.0)
Ph3N (1.0)
DBU (1.0)
DMAP (1.0)
85 : 15
75 : 25
85 : 15
—
—
—
91
49
Trace
Trace
Trace
Trace
(CH2Cl)2 45
(CH2Cl)2 45
(CH2Cl)2 45
(CH2Cl)2 45
—
a Reaction conditions: 4-methylphenol (1b, 1.1 mmol), 3-phenyl-
propiolonitrile (2a, 1.0 mmol), solvent (2.0 mL), base (amount in
Table 1) at the temperature indicated in Table 1, 12 h. b Isolated yield.
DMF = N,N-dimethylformamide, DMAc = N,N-dimethylacetamide,
rt = 20–25 °C.
reactions of 4-methylphenol with 3-(4-tert-butylphenyl)-, 3-(4-
methoxyphenyl)- and 3-(4-chlorophenyl)-propiolonitriles pro-
ceeded well and generated the corresponding products in good
yields with the ratios of E : Zfrom 85 : 15 to 77 : 23 (Table 2,
entries 15′–17′). It is important to note that 3-aliphatic propiolo-
nitriles, such as non-2-ynenitrile and hept-2-ynenitrile also
reacted with 4-methylphenol to generate the corresponding pro-
ducts in good yields and good regio- and stereoselectivity
(Table 2, entries 18′ and 19′). However, no desired product was
found when 4-methylphenol reacted with 3-(2-methylphenyl)-
propiolonitrile (Table 2, entry 20′). X-ray crystallographic analy-
sis of 3j confirmed its structure16 and showed that the dihedral
angel of the phenol ring and vinyl plane is 77.78°.
With the addition products (E)-3-aryloxy-acrylonitriles and
(Z)-3-aryloxy-acrylonitriles in our hands, transformation of them
into the corresponding 3-cyanobenzofurans was examined via
palladium-catalyzed direct C–H bond activation. The results are
summarized in Table 3. Firstly, the effect of solvent on the
model reaction of 3b was investigated, and a significant solvent
effect was observed. Dioxane was found to be the best among
the solvents tested (Table 3, entries 1–7). The effect of palladium
catalytic systems was also examined, and the results indicated
that Pd(OAc)2–PPh3 system displayed the highest reactivity
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Table 2 Base-promoted addition reactions of phenols to
Table 3 Optimization of the reaction conditions for palladium-
catalyzed intramolecular cyclization of (E)-3-phenyl-3-(p-tolyloxy)-
acrylonitrile (3b)a
propiolonitrilesa,b
Entry R1
R
Yieldc (3 + 3′) (%) E : Z ratio
1
1′
2
2′
3
3′
4
4′
5
5′
6
6′
7
7′
8
8′
H
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
C6H5
3a + 3a′, 99
3a + 3a′, 96
3b + 3b′, 99
3b + 3b′, 97
3c + 3c′, 98
3c + 3c′, 94
3d + 3d′, 93
3d + 3d′, 89
3e + 3e′, 98
3e + 3e′, 91
3f + 3f′, 99
3f + 3f′, 93
3g + 3g′, 97
3g + 3g′, 95
3h + 3h′, 95
3h + 3h′, 94
3i + 3i′, 99
3i + 3i′, 95
3j + 3j′, 99
3j + 3j′, 98
3k + 3k′, 96
3k + 3k′, 94
3l + 3l′, 99
3l + 3l′, 93
3m + 3m′, 96
3m + 3m′, 91
3n + 3n′, 96
3n + 3n′, 96
0 : 100
85 : 15
0 : 100
83 : 17
0 : 100
81 : 19
0 : 100
78 : 22
0 : 100
83 : 17
0 : 100
84 : 16
0 : 100
80 : 20
0 : 100
74 : 26
0 : 100
91 : 9
Entry Pd catal.
Ligand Solvent
Oxidant
Yieldb (%)
p-CH3
1
2
3
4
5
6
7
8
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(PPh3)2Cl2
Pd(CH3CN)2Cl2
Pd(PPh3)4
Pd(PCy3)2Cl2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
Pd(OAc)2
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
dppf
dppe
DMF
Cu(OAc)2 81
Cu(OAc)2 74
Cu(OAc)2
Cu(OAc)2 13
Cu(OAc)2 27
DMAc
i-PrOH
DMSO
NMP
Toluene Cu(OAc)2 18
Dioxane Cu(OAc)2 92
Dioxane Cu(OAc)2 47
Dioxane Cu(OAc)2 54
m-CH3
o-CH3
0
p-C2H5
p-(i-C3H7)
p-(t-C4H9)
p-CH3O
p-Cl
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
Pn-Bu3 Dioxane Cu(OAc)2 68
—
—
—
—
Dioxane Cu(OAc)2 61
Dioxane Cu(OAc)2 81
Dioxane Cu(OAc)2 73
Dioxane Cu(OAc)2 58
Dioxane Cu(OAc)2 67
Dioxane Cu(OTf)2 59
Dioxane CuCl2
Dioxane CuBr2
Dioxane CuSO4
Dioxane Ag2O
Dioxane K2S2O8
Dioxane TBHP
Dioxane O2
9
9′
—
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
PPh3
10
10′
11
11′
12
12′
13
13′
14
14′
15
15′
16
16′
17
17′
18
18′
19
19′
20
20′
p-NO2
0 : 100
93 : 7
0
0
0
17
0
0
0
p-C6H5CO
0 : 100
90 : 10
0 : 100
80 : 20
0 : 100
87 : 13
0 : 100
70 : 30
0 : 100
82 : 18
0 : 100
77 : 23
0 : 100
85 : 15
0 : 100
80 : 20
0 : 100
81 : 19
0 : 100
—
m,m-(CH3)2 C6H5
p-Cl-m-CH3 C6H5
a Reaction conditions: (E)-3-phenyl-3-(p-tolyloxy)acrylonitrile (3b,
1.0 mmol), Pd catalyst (5.0 mol%), ligand (10.0 mol%) if necessary,
solvent (2.0 mL), oxidant (2.0 mmol) at 130 °C, 16 h. b Isolated yield.
DMF = N,N-dimethylformamide, DMAc = N,N-dimethylacetamide,
DMSO = dimethyl sulfoxide, NMP = N-methyl-2-pyrrolidone, dppf =
α-naphthyl
p-CH3
p-CH3
p-CH3
p-CH3
p-CH3
p-CH3
C6H5
p-(t-C4H9)C6H4 3o + 3o′, 97
3o + 3o′, 91
p-CH3OC6H4
p-ClC6H4
n-C6H13
3p + 3p′, 95
3p + 3p′, 90
3q + 3q′, 98
3q + 3q′, 92
3r + 3r′, 93
3r + 3r′, 85
3s + 3s′, 91
3s + 3s′, 82
3t + 3t′, 62
3t + 3t′, 0
1,1′-bis(diphenylphosphino)ferrocene, dppe
phosphino)ethane, TBHP = tert-butyl hydroperoxide.
=
1,2-bis(diphenyl-
substrates 3 derived from 3-phenylpropiolonitrile and phenols
with an electron-donating or electron-withdrawing group were
able to make the reaction proceed smoothly, and afforded the
corresponding products 4a–k in 64–92% yields. The yields of
products from substrates prepared from phenols with electron-
donating groups were greater than those from substrates prepared
from phenols with electron-withdrawing groups (Scheme 3,
4a–h vs. 4i–k). It should be noted that the reaction could tolerate
an ortho-substituted group (4d). When two positions of phenol
were occupied with Me/Me or Cl/Me groups, good yields of 4l
and 4m were obtained. Substrate 3n from α-naphthalenol also
generated 4n in 81% yield. When substrates 3o and 3q from
4-methylphenol and 3-(4-tert-butylphenyl)-propiolonitrile and
3-(4-chlorophenyl)-propiolonitrile also underwent the reaction,
82, and 84% yields of 4o and 4q were obtained. It is worth
noting that only 6-substituted-3-cyanobenzofuran isomers (4c, 4l
and 4m) were observed when substrates were prepared from
3-substituted phenols with propiolonitrile. The reactions of 3r
and 3s also underwent the cyclization to generate 4r and 4s in
74 and 70% yields, respectively. However, when 3p was used as
substrate, no desired cyclization product 4p was isolated. It is
important to note that the reactions of 3i–k in DMF were
superior to those in dioxane.
n-C4H9
o-CH3C6H4
a For entries 1–20: phenol (1, 1.1 mmol), propiolonitrile (2, 1.0 mmol),
Na2CO3 (1.0 mmol), DMF (2.0 mL) at room temperature, 12 h. b For
entries 1′–20′: phenol (1, 1.1 mmol), propiolonitrile (2, 1.0 mmol),
DABCO (1.0 mmol), DCE (2.0 mL) at 45 °C, 12 h. c Isolated yields.
(Table 3, entries 8–15). The oxidant also played an important
role in the reaction. Cu(OAc)2 was found to be the best among
the oxidants examined (Table 3, entries 16–23). So, the opti-
mized reaction conditions were found to be Pd(OAc)2–PPh3–Cu-
(OAc)2–dioxane at 130 °C for 16 h. It should be noted that when
(Z)-3-aryloxy-acrylonitrile 3b′ was used as a substrate under the
same reaction conditions, no desired cyclization product was
detected, and starting material was unchanged and recovered.
Under the optimized cyclization reaction conditions, (E)-
3-aryloxy-3-substituted acrylonitriles 3a–o and 3q–s, underwent
palladium-catalyzed intramolecular cyclization well via the
direct C–H bond activation to afford the desired 3-cyanobenzo-
furans, 4a–o and 4q–s. As can be seen from Scheme 3,
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Scheme 4 Proposed reaction mechanism.
reaction to remove DABCO via a simple separation, it was possi-
ble to proceed with the intramolecular cyclization of 3-aryloxy-
acrylonitriles, providing comparable total yields of desired
products (Scheme 3). It is important to note that this procedure
eliminated the column chromatographic separation of the
mixture of (Z)-3-aryloxy-acrylonitriles and (E)-3-aryloxy-
acrylonitriles.
A possible reaction mechanism is proposed in Scheme 4.
First, an intermolecular nucleophilic addition of phenol to pro-
piolonitrile promoted by DABCO generated (E)-3-aryloxy-acryl-
onitrile (3) with good regio- and stereo-selectivity.15,17
Subsequently, the formed 3 reacted with Pd(OAc)2 to form a
vinylpalladium intermediate I through electrophilic palladation
via C–H activation of the vinyl proton,18 which underwent intra-
molecular electrophilic aromatic palladation via C–H activation
of the aromatic hydrogen to give an intermediate II.19 Carbon–
carbon bond formation via reductive elimination of II, afforded
the corresponding product 3-cyanobenzofuran (4) and Pd0. And
finally, the oxidation of Pd0 by the oxidant Cu(OAc)2 regener-
ated the PdII species to complete the catalytic cycle. Moreover,
the structure of product 4j was further confirmed by X-ray
crystallography.20
Conclusion
In conclusion, a series of organic transformations of simple
phenols and propiolonitriles was developed, including (1) a
Na2CO3-promoted addition of phenols to propiolonitriles gener-
ating (Z)-3-aryloxy-acrylonitriles in almost quantitative yields
with exclusively Z-isomers; (2) a DABCO-promoted addition
reaction of phenols to propiolonitriles affording mainly (E)-
3-aryloxy-acrylonitriles with high yields; (3) a palladium-cata-
lyzed intramolecular cyclization of (E)-3-aryloxy-acrylonitriles
giving 3-cyanobenzofurans in good yields through direct C–H
bond functionalization. It provides a novel, efficient and practical
approach to (Z)-3-aryloxy-acrylonitriles, (E)-3-aryloxy-acrylo-
nitriles and 3-cyanobenzofurans under mild reaction conditions.
Scheme 3 Palladium-catalyzed synthesis of 3-cyanobenzofurans.
To simplify the procedure and increase the novelty of this
study, we tried to develop a one-pot procedure for benzofuran
preparation directly from alkynes and propiolonitriles, instead of
sequential operation and avoiding isolation of the intermediate
vinyl derivatives. However, no satisfactory results were obtained
by using one-pot procedures for benzofuran preparation directly
from alkynes and propiolonitriles. To our delight, when the reac-
tion of phenol with propiolonitrile in the presence of DABCO
was neutralized with HCl (1.0 mol L−1, aq.) after the addition
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funnel, and concentrated under reduced pressure. The residue
was purified by flash chromatography on silica gel to give
5-methyl-2-phenylbenzofuran-3-carbonitrile, 4b, in 92% yield.
Experimental section
All the chemicals and solvents were purchased from commercial
suppliers and used without further purification. 1H NMR,
13C NMR spectra were measured on a Bruker Avance NMR
spectrometer (400 MHz or 100 MHz, respectively) with CDCl3
as solvent and recorded in ppm relative to internal tetramethyl-
silane standard. The peak patterns are indicated as follows: s,
singlet; d, doublet; t, triplet; m, multiplet; q, quartet. The coup-
ling constants, J, are reported in Hertz (Hz). High resolution
mass spectroscopy data of the product were collected on a
Waters Micromass GCT instrument.
(E)-3-Phenoxy-3-phenylacrylonitrile, 3a. Colorless oil. 1H
NMR (400 MHz, CDCl3): δ 8.02–8.00 (m, 2H), 7.56–7.45 (m,
5H), 7.33–7.29 (m, 1H), 7.16–7.14 (m, 2H), 4.56 (s, 1H); 13C
NMR (100 MHz, CDCl3): δ 172.63, 153.28, 131.83, 131.49,
130.29, 128.52, 127.94, 126.26, 121.01, 117.90, 75.05. IR (KBr,
cm−1): 2215 (νCuN). HRMS (EI) ([M]+) Calcd for C15H11NO:
221.0841, Found: 221.0840.
Typical procedure for Na2CO3-promoted addition reaction of
phenol to propiolonitrile
Under an air atmosphere, a sealable reaction tube equipped
with a magnetic stir bar was charged with 4-methylphenol
(1.1 mmol), 3-phenylpropiolonitrile (1.0 mmol), Na2CO3
(1.0 mmol) and DMF (2.0 mL). The rubber septum was then
replaced by a Teflon-coated screw cap, and the reaction vessel
placed in air bath at room temperature for 12 h. After the reaction
was completed, it was diluted with ethyl acetate. The resulting
solution was directly filtered through a pad of silica gel using a
sintered glass funnel, and concentrated under reduced pressure.
The residue was purified by flash chromatography on silica gel
to give (Z)-3-phenyl-3-(p-tolyloxy)acrylonitrile (3b′) in 99%
yield.
(Z)-3-Phenoxy-3-phenylacrylonitrile, 3a′. Colorless oil. 1H
NMR (400 MHz, CDCl3): δ 7.59–7.56 (m, 2H), 7.47–7.43 (m,
1H), 7.41–7.37 (m, 2H), 7.34–7.30 (m, 2H), 7.14–7.10 (m, 1H),
7.06–7.03 (m, 2H), 5.44 (s, 1H); 13C NMR (100 MHz, CDCl3):
δ 168.29, 155.61, 132.05, 131.39, 129.66, 128.84, 126.83,
124.11, 118.03, 115.07, 81.83. IR (KBr, cm−1): 2218 (νCuN).
HRMS (EI) ([M]+) Calcd for C15H11NO: 221.0841, Found:
221.0842.
Typical procedure for DABCO-promoted addition reaction of
phenol to propiolonitrile
Under an air atmosphere, a sealable reaction tube equipped
with a magnetic stir bar was charged with 4-methylphenol
(1.1 mmol), 3-phenylpropiolonitrile (1.0 mmol), DABCO
(1.0 mmol) and ClCH2CH2Cl (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 45 °C for 12 h. After the reaction
was completed, it was cooled to room temperature and diluted
with ethyl acetate. The resulting solution was directly filtered
through a pad of silica gel using a sintered glass funnel, and con-
centrated under reduced pressure. The residue was purified
by flash chromatography on silica gel to give (Z)-3-phenyl-3-(p-
tolyloxy)acrylonitrile (3b′) and (E)-3-phenyl-3-(p-tolyloxy)-
acrylonitrile (3b).
1
(E)-3-Phenyl-3-(p-tolyloxy)acrylonitrile, 3b. Colorless oil. H
NMR (400 MHz, CDCl3): δ 7.99 (d, J = 7.6 Hz, 2H), 7.57–7.50
(m, 3H), 7.26 (d, J = 8.4 Hz, 2H), 7.02 (d, J = 7.6 Hz, 2H), 4.55
(s, 1H), 2.40 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 172.98,
151.07, 136.13, 132.02, 131.47, 130.80, 128.55, 127.98, 120.81,
118.12, 74.63, 20.84. IR (KBr, cm−1): 2215 (νCuN). HRMS (EI)
([M]+) Calcd for C16H13NO: 235.0997, Found: 235.0992.
Typical procedure for palladium-catalyzed intramolecular
cyclization of (E)-3-aryloxy-acrylonitrile
Under an air atmosphere, a sealable reaction tube equipped with
a magnetic stirrer bar was charged with (E)-3-phenyl-3-(p-toly-
loxy)acrylonitrile (3b, 1.0 mmol), Pd(OAc)2 (0.05 mmol), PPh3
(0.10 mmol), Cu(OAc)2 (2.0 mmol) and dioxane (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 130 °C for 16 h.
After the reaction was completed, it was cooled to room temp-
erature and diluted with ethyl acetate. The resulting solution was
directly filtered through a pad of silica gel using a sintered glass
1
(Z)-3-Phenyl-3-(p-tolyloxy)acrylonitrile, 3b′. Colorless oil. H
NMR (400 MHz, CDCl3): δ 7.56 (d, J = 7.6 Hz, 2H), 7.46–7.36
(m, 3H), 7.10 (d, J = 7.6 Hz, 2H), 6.92 (d, J = 7.6 Hz, 2H), 5.37
(s, 1H), 2.30 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 168.66,
153.50, 133.86, 132.39, 131.34, 130.15, 128.84, 126.91, 118.07,
115.18, 81.03, 20.67. IR (KBr, cm−1): 2219 (νCuN). HRMS (EI)
7188 | Org. Biomol. Chem., 2012, 10, 7184–7196
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([M]+) Calcd for C16H13NO: 235.0997, Found: 235.1001.
for C16H13NO: 235.0997, Found: 235.0994.
(E)-3-(4-Ethylphenoxy)-3-phenylacrylonitrile, 3e. White solid,
m.p. 48–50 °C. H NMR (400 MHz, CDCl3): δ 8.04–8.02 (m,
1
(E)-3-Phenyl-3-(m-tolyloxy)acrylonitrile, 3c. Colorless oil. H
NMR (400 MHz, CDCl3): δ 8.02–8.00 (m, 2H), 7.57–7.50 (m,
3H), 7.37–7.33 (m, 1H), 7.12 (d, J = 7.6 Hz, 1H), 6.97–6.94 (m,
2H), 4.57 (s, 1H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 172.69, 153.25, 140.66, 131.93, 131.42, 129.94, 128.49,
127.91, 127.02, 121.54, 118.01, 117.92, 74.81, 21.21. IR (KBr,
cm−1): 2215 (νCuN). HRMS (EI) ([M]+) Calcd for C16H13NO:
235.0997, Found: 235.0998.
1
2H), 7.57–7.49 (m, 3H), 7.29 (d, J = 8.8 Hz, 2H), 7.06 (d, J =
8.4 Hz, 2H), 4.57 (s, 1H), 2.70 (q, J = 7.6 Hz, 2H), 1.29 (t, J =
7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 172.77, 151.04,
142.27, 131.89, 131.32, 129.48, 128.39, 127.84, 120.73, 117.96,
74.49, 28.07, 15.40. IR (KBr, cm−1): 2214 (νCuN). HRMS (EI)
([M]+) Calcd for C17H15NO: 249.1154, Found: 249.1153.
(Z)-3-(4-Ethylphenoxy)-3-phenylacrylonitrile, 3e′. Colorless
oil. 1H NMR (400 MHz, CDCl3): δ 7.59–7.56 (m, 2H),
7.47–7.43 (m, 1H), 7.41–7.37 (m, 2H), 7.15–7.12 (m, 2H),
6.98–6.94 (m, 2H), 5.40 (s, 1H), 2.61 (q, J = 7.6 Hz, 2H), 1.22
(t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 168.52,
153.59, 140.05, 132.23, 131.28, 128.89, 128.78, 126.83, 117.89,
115.14, 81.31, 27.95, 15.45. IR (KBr, cm−1): 2218 (νCuN).
HRMS (EI) ([M]+) Calcd for C17H15NO: 249.1154, Found:
249.1152.
1
(Z)-3-Phenyl-3-(m-tolyloxy)acrylonitrile, 3c′. Colorless oil. H
NMR (400 MHz, CDCl3): δ 7.59–7.57 (m, 2H), 7.47–7.43 (m,
1H), 7.41–7.37 (m, 2H), 7.20–7.16 (m, 1H), 6.94–6.89 (m, 2H),
6.83–6.80 (m, 1H), 5.43 (s, 1H), 2.33 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 168.29, 155.59, 139.91, 132.13, 131.33,
129.28, 128.81, 126.77, 124.89, 118.58, 115.13, 114.88, 81.76,
21.28. IR (KBr, cm−1): 2218 (νCuN). HRMS (EI) ([M]+) Calcd
for C16H13NO: 235.0997, Found: 235.0999.
1
(E)-3-Phenyl-3-(o-tolyloxy)acrylonitrile, 3d. Colorless oil. H
(E)-3-(4-iso-Propylphenoxy)-3-phenylacrylonitrile, 3f. Color-
less oil. 1H NMR (400 MHz, CDCl3): δ 8.03–8.01 (m, 2H),
7.57–7.50 (m, 3H), 7.32 (d, J = 8.4 Hz, 2H), 7.07 (d, J = 8.4
Hz, 2H), 4.58 (s, 1H), 3.02–2.92 (m, 1H), 1.31 (s, 3H), 1.29 (s,
3H); 13C NMR (100 MHz, CDCl3): δ 172.82, 151.12, 146.98,
131.97, 131.38, 128.46, 128.12, 127.90, 120.77, 118.03, 74.55,
33.50, 23.90. IR (KBr, cm−1): 2211 (νCuN). HRMS (EI) ([M]+)
Calcd for C18H17NO: 263.1310, Found: 263.1307.
NMR (400 MHz, CDCl3): δ 8.07–8.04 (m, 2H), 7.58–7.52 (m,
3H), 7.35–7.29 (m, 2H), 7.26–7.22 (m, 1H), 7.08–7.06 (m, 1H),
4.41 (s, 1H), 2.28 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 171.74, 151.19, 131.96, 131.82, 131.50, 130.07, 128.55,
127.83, 127.80, 126.61, 121.32, 118.07, 73.45, 15.67. IR (KBr,
cm−1): 2215 (νCuN). HRMS (EI) ([M]+) Calcd for C16H13NO:
235.0997, Found: 235.0999.
1
(Z)-3-Phenyl-3-(o-tolyloxy)acrylonitrile, 3d′. Colorless oil. H
NMR (400 MHz, CDCl3): δ 7.63–7.61 (m, 2H), 7.51–7.47 (m,
1H), 7.44–7.41 (m, 2H), 7.28–7.26 (m, 1H), 7.15–7.09 (m, 2H),
6.87–6.85 (m, 1H), 5.33 (s, 1H), 2.43 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 168.35, 153.56, 132.55, 131.42, 131.33,
128.89, 128.85, 126.97, 126.52, 125.01, 118.31, 114.75, 78.42,
16.04. IR (KBr, cm−1): 2213 (νCuN). HRMS (EI) ([M]+) Calcd
(Z)-3-(4-iso-Propylphenoxy)-3-phenylacrylonitrile, 3f′. Color-
less oil. 1H NMR (400 MHz, CDCl3): δ 7.59–7.56 (m, 2H),
7.47–7.36 (m, 3H), 7.18–7.14 (m, 2H), 6.98–6.94 (m, 2H), 5.41
(s, 1H), 2.93–2.83 (m, 1H), 1.24 (s, 3H), 1.22 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 168.46, 153.63, 144.63, 132.24, 131.29,
128.80, 127.48, 126.83, 117.75, 115.14, 81.57, 33.27, 23.93. IR
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(KBr, cm−1): 2219 (νCuN). HRMS (EI) ([M]+) Calcd for
(νCuN). HRMS (EI) ([M]+) Calcd for C16H13NO2: 251.0946,
C18H17NO: 263.1310, Found: 263.1309.
Found: 251.0948.
(E)-3-(4-tert-Butylphenoxy)-3-phenylacrylonitrile, 3g. White
solid, m.p. 102–104 °C. 1H NMR (400 MHz, CDCl3):
δ 8.03–8.01 (m, 2H), 7.57–7.47 (m, 5H), 7.08–7.05 (m, 2H),
4.58 (s, 1H), 1.37 (s, 9H); 13C NMR (100 MHz, CDCl3):
δ 172.82, 150.91, 149.33, 132.02, 131.43, 128.51, 127.94,
127.15, 120.45, 118.07, 74.62, 34.50, 31.31. IR (KBr, cm−1):
2213 (νCuN). HRMS (EI) ([M]+) Calcd for C19H19NO:
277.1467, Found: 277.1473.
(E)-3-(4-Chlorophenoxy)-3-phenylacrylonitrile, 3i. White
solid, m.p. 76–78 °C. 1H NMR (400 MHz, CDCl3): δ 7.98–7.95
(m, 2H), 7.57–7.49 (m, 3H), 7.44–7.41 (m, 2H), 7.10–7.06 (m,
2H), 4.58 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 172.21,
151.82, 131.63, 131.59, 131.45, 130.37, 128.57, 127.92, 122.32,
117.46, 75.83. IR (KBr, cm−1): 2212 (νCuN). HRMS (EI)
([M]+) Calcd for C15H10NOCl: 255.0451, Found: 255.0452.
(Z)-3-(4-Chlorophenoxy)-3-phenylacrylonitrile, 3i′. White
solid, m.p. 53–55 °C. 1H NMR (400 MHz, CDCl3): δ 7.54–7.52
(m, 2H), 7.48–7.44 (m, 1H), 7.41–7.37 (m, 2H), 7.27–7.24 (m,
2H), 6.97–6.93 (m, 2H), 5.46 (s, 1H); 13C NMR (100 MHz,
CDCl3): δ 167.96, 154.24, 131.64, 129.72, 129.22, 129.00,
126.83, 119.14, 114.88, 82.77. IR (KBr, cm−1): 2219 (νCuN).
HRMS (EI) ([M]+) Calcd for C15H10NOCl: 255.0451, Found:
255.0450.
(Z)-3-(4-tert-Butylphenoxy)-3-phenylacrylonitrile, 3g′. White
solid, m.p. 79–81 °C. 1H NMR (400 MHz, CDCl3): δ 7.59–7.57
(m, 2H), 7.47–7.39 (m, 3H), 7.34–7.30 (m, 2H), 6.98–6.94 (m,
2H), 5.42 (s, 1H), 1.30 (s, 9H); 13C NMR (100 MHz, CDCl3):
δ 168.41, 153.40, 146.87, 132.23, 131.31, 128.82, 126.83,
126.47, 117.28, 115.14, 81.86, 34.19, 31.29. IR (KBr, cm−1):
2219 (νCuN). HRMS (EI) ([M]+) Calcd for C19H19NO:
277.1467, Found: 277.1469.
(E)-3-(4-Methoxyphenoxy)-3-phenylacrylonitrile, 3h. White
solid, m.p. 62–64 °C. 1H NMR (400 MHz, CDCl3): δ 8.00–7.98
(m, 2H), 7.57–7.49 (m, 3H), 7.07–7.04 (m, 2H), 6.99–6.96 (m,
2H), 4.53 (s, 1H), 3.84 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 173.28, 157.61, 146.59, 132.00, 131.48, 128.54, 127.96,
122.05, 118.15, 115.24, 74.35, 55.61. IR (KBr, cm−1): 2210
(νCuN). HRMS (EI) ([M]+) Calcd for C16H13NO2: 251.0946,
Found: 251.0949.
(E)-3-(4-Nitrophenoxy)-3-phenylacrylonitrile, 3j. White solid,
m.p. 87–89 °C. H NMR (400 MHz, CDCl3): δ 8.32–8.28 (m,
1
2H), 7.92–7.89 (m, 2H), 7.57–7.48 (m, 3H), 7.25–7.22 (m, 2H),
4.90 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 170.41, 158.88,
144.84, 132.08, 130.65, 128.89, 128.06, 126.14, 120.60, 116.66,
80.05. IR (KBr, cm−1): 2213 (νCuN). HRMS (EI) ([M]+) Calcd
for C15H10N2O3: 266.0691, Found: 266.0692.
(Z)-3-(4-Methoxyphenoxy)-3-phenylacrylonitrile, 3h′. White
solid, m.p. 71–73 °C. 1H NMR (400 MHz, CDCl3): δ 7.58–7.56
(m, 2H), 7.47–7.37 (m, 3H), 7.01–6.97 (m, 2H), 6.85–6.82 (m,
2H), 5.31 (s, 1H), 3.77 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 168.99, 156.36, 149.19, 132.44, 131.29, 128.78, 126.89,
119.65, 115.14, 114.59, 79.76, 55.48. IR (KBr, cm−1): 2205
(Z)-3-(4-Nitrophenoxy)-3-phenylacrylonitrile, 3j′. White solid,
m.p. 78–80 °C. H NMR (400 MHz, CDCl3): δ 8.21–8.17 (m,
2H), 7.54–7.47 (m, 3H), 7.44–7.39 (m, 2H), 7.12–7.08 (m, 2H),
5.68 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 166.77, 160.40,
143.49, 132.16, 130.64, 129.28, 126.57, 125.94, 117.35, 114.43,
85.27. IR (KBr, cm−1): 2224 (νCuN). HRMS (EI) ([M]+) Calcd
1
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for C15H10N2O3: 266.0691, Found: 266.0689.
81.77, 21.23. IR (KBr, cm−1): 2214 (νCuN). HRMS (EI) ([M]+)
Calcd for C17H15NO: 249.1154, Found: 249.1155.
(E)-3-(4-Benzoylphenoxy)-3-phenylacrylonitrile,
3k. White
(E)-3-(4-Chloro-3-methylphenoxy)-3-phenyl-acrylonitrile, 3m.
White solid, m.p. 65–67 °C. 1H NMR (400 MHz, CDCl3):
δ 7.99–7.96 (m, 2H), 7.57–7.48 (m, 3H), 7.41 (d, J = 8.8 Hz,
1H), 7.03 (d, J = 2.8 Hz, 1H), 6.93–6.90 (m, 1H), 4.59 (s, 1H),
2.41 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 172.33, 151.64,
138.51, 131.73, 131.59, 131.56, 130.55, 128.54, 127.90, 123.27,
119.61, 117.60, 75.49, 20.14. IR (KBr, cm−1): 2213 (νCuN).
HRMS (EI) ([M]+) Calcd for C16H12NOCl: 269.0607, Found:
269.0612.
solid, m.p. 118–112 °C. 1H NMR (400 MHz, CDCl3):
δ 7.98–7.95 (m, 2H), 7.91 (d, J = 8.4 Hz, 2H), 7.81–7.79 (m,
2H), 7.64–7.60 (m, 1H), 7.54–7.49 (m, 5H), 7.22 (d, J = 8.4 Hz,
2H), 4.77 (s, 1H); 13C NMR (100 MHz, CDCl3): δ 194.99,
171.43, 156.83, 137.04, 135.02, 132.56, 132.43, 131.72, 131.25,
129.77, 128.64, 128.30, 127.97, 120.40, 117.23, 77.45. IR (KBr,
cm−1): 2212 (νCuN), 1653 (νCvO). HRMS (EI) ([M]+) Calcd for
C22H15NO2: 325.1103, Found: 325.1104.
(Z)-3-(4-Chloro-3-methylphenoxy)-3-phenyl-acrylonitrile, 3m′.
White solid, m.p. 51–53 °C. 1H NMR (400 MHz, CDCl3):
δ 7.55–7.53 (m, 2H), 7.48–7.37 (m, 3H), 7.22 (d, J = 8.8 Hz,
1H), 6.92 (d, J = 2.8 Hz, 1H), 6.78–6.75 (m, 1H), 5.46 (s, 1H),
2.32 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 167.96, 154.07,
137.70, 131.71, 131.56, 129.86, 129.33, 128.94, 126.78, 120.08,
116.32, 114.98, 82.70, 20.19. IR (KBr, cm−1): 2219 (νCuN).
HRMS (EI) ([M]+) Calcd for C16H12NOCl: 269.0607, Found:
269.0605.
(Z)-3-(4-Benzoylphenoxy)-3-phenylacrylonitrile, 3k′. White
solid, m.p. 97–99 °C. 1H NMR (400 MHz, CDCl3): δ 7.79–7.73
(m, 4H), 7.59–7.54 (m, 3H), 7.48–7.44 (m, 3H), 7.41–7.37 (m,
2H), 7.10–7.06 (m, 2H), 5.60 (s, 1H); 13C NMR (100 MHz,
CDCl3): δ 195.16, 167.30, 158.95, 137.37, 132.91, 132.28,
132.24, 131.77, 131.21, 129.70, 129.06, 128.18, 126.66, 116.97,
114.77, 84.22. IR (KBr, cm−1): 2216 (νCuN), 1657 (νCvO).
HRMS (EI) ([M]+) Calcd for C22H15NO2: 325.1103, Found:
325.1106.
(E)-3-(3,5-Dimethylphenoxy)-3-phenylacrylonitrile, 3l. Color-
less oil. 1H NMR (400 MHz, CDCl3): δ 8.02–7.99 (m, 2H),
7.57–7.50 (m, 3H), 6.95 (s, 1H), 6.77 (s, 2H), 4.58 (s, 1H), 2.37
(s, 6H); 13C NMR (100 MHz, CDCl3): δ 172.75, 153.25,
140.25, 132.05, 131.38, 128.48, 127.90, 127.89, 118.51, 118.13,
74.62, 21.14. IR (KBr, cm−1): 2215 (νCuN). HRMS (EI) ([M]+)
Calcd for C17H15NO: 249.1154, Found: 249.1158.
(E)-3-(Naphthalen-1-yloxy)-3-phenylacrylonitrile, 3n. White
solid, m.p. 80–82 °C. H NMR (400 MHz, CDCl3): δ 8.18 (d,
1
J = 8.0 Hz, 2H), 7.97–7.93 (m, 2H), 7.83 (d, J = 8.4 Hz, 1H),
7.61–7.51 (m, 6H), 7.27 (d, J = 7.2 Hz, 1H), 4.50 (s, 1H); 13C
NMR (100 MHz, CDCl3): δ 172.36, 148.97, 135.00, 131.75,
131.66, 128.70, 128.24, 127.92, 127.02, 127.01, 126.56, 126.00,
125.68, 120.99, 117.85, 117.55, 75.17. IR (KBr, cm−1): 2212
(νCuN). HRMS (EI) ([M]+) Calcd for C19H13NO: 271.0997,
Found: 271.1001.
(Z)-3-(3,5-Dimethylphenoxy)-3-phenylacrylonitrile, 3l′. Color-
less oil. 1H NMR (400 MHz, CDCl3): δ 7.59–7.57 (m, 2H),
7.47–7.37 (m, 3H), 6.75 (s, 1H), 6.66 (s, 2H), 5.42 (s, 1H), 2.27
(s, 6H); 13C NMR (100 MHz, CDCl3): δ 168.30, 155.65,
139.49, 132.31, 131.31, 128.82, 126.77, 125.81, 115.54, 115.19,
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(Z)-3-(Naphthalen-1-yloxy)-3-phenylacrylonitrile, 3n′. White
solid, m.p. 71–73 °C. 1H NMR (400 MHz, CDCl3): δ 8.39–8.37
(m, 1H), 7.90 (d, J = 7.6 Hz, 1H), 7.65–7.58 (m, 5H), 7.46–7.42
(m, 1H), 7.37–7.27 (m, 3H), 6.86 (d, J = 7.6 Hz, 1H), 5.52 (s,
1H); 13C NMR (100 MHz, CDCl3): δ 168.36, 151.35, 134.61,
132.00, 131.51, 128.94, 127.91, 126.85, 126.46, 125.66, 125.20,
124.24, 121.28, 114.99, 112.35, 82.01. IR (KBr, cm−1): 2218
(νCuN). HRMS (EI) ([M]+) Calcd for C19H13NO: 271.0997,
Found: 271.0995.
C17H15NO2: 265.1103, Found: 265.1105.
(Z)-3-(4-Methoxyphenyl)-3-(p-tolyloxy)acrylonitrile, 3p′.
White solid, m.p. 39–41 °C. 1H NMR (400 MHz, CDCl3):
δ 7.50 (d, J = 8.8 Hz, 2H), 7.09 (d, J = 8.4 Hz, 2H), 6.92–6.86
(m, 4H), 5.29 (s, 1H), 3.82 (s, 3H), 2.30 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 168.33, 161.98, 153.70, 133.44, 130.06,
128.54, 124.44, 117.71, 114.18, 114.16, 79.45, 55.30, 20.58. IR
(KBr, cm−1): 2216 (νCuN). HRMS (EI) ([M]+) Calcd for
C17H15NO2: 265.1103, Found: 265.1102.
(E)-3-(4-tert-Butylphenyl)-3-(p-tolyloxy)acrylonitrile,
3o.
White solid, m.p. 93–95 °C. 1H NMR (400 MHz, CDCl3):
δ 7.97 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.26 (d, J =
8.4 Hz, 2H), 7.02 (d, J = 8.4 Hz, 2H), 4.52 (s, 1H), 2.40 (s, 3H),
1.39 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 172.84, 154.89,
151.04, 135.90, 130.68, 129.10, 127.67, 125.42, 120.75, 118.29,
73.81, 34.84, 30.98, 20.74. IR (KBr, cm−1): 2210 (νCuN).
HRMS (EI) ([M]+) Calcd for C20H21NO: 291.1623, Found:
291.1626.
(E)-3-(4-Chlorophenyl)-3-(p-tolyloxy)acrylonitrile, 3q. White
solid, m.p. 89–81 °C. H NMR (400 MHz, CDCl3): δ 7.94 (d,
1
J = 8.8 Hz, 2H), 7.47 (d, J = 8.4 Hz, 2H), 7.25 (d, J = 8.0 Hz,
2H), 7.00 (d, J = 8.4 Hz, 2H), 4.56 (s, 1H), 2.39 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 171.56, 150.73, 137.41, 136.19,
130.76. 130.32, 129.25, 128.72, 120.64, 117.73, 74.83, 20.74.
IR (KBr, cm−1): 2210 (νCuN). HRMS (EI) ([M]+) Calcd for
C16H12NOCl: 269.0607, Found: 269.0610.
(Z)-3-(4-tert-Butylphenyl)-3-(p-tolyloxy)acrylonitrile,
3o′.
White solid, m.p. 76–78 °C. 1H NMR (400 MHz, CDCl3):
δ 7.52 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz, 2H), 7.11 (d, J =
8.4 Hz, 2H), 6.94 (d, J = 8.4 Hz, 2H), 5.37 (s, 1H), 2.31 (s, 3H),
1.32 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 168.56, 155.02,
153.69, 133.63, 130.13, 129.44, 126.60, 125.83, 117.87, 115.39,
80.38, 34.88, 31.00, 20.68. IR (KBr, cm−1): 2221 (νCuN).
HRMS (EI) ([M]+) Calcd for C20H21NO: 291.1623, Found:
291.1622.
(Z)-3-(4-Chlorophenyl)-3-(p-tolyloxy)acrylonitrile, 3q′. White
solid, m.p. 77–79 °C. H NMR (400 MHz, CDCl3): δ 7.51 (d,
1
J = 8.4 Hz, 2H), 7.36 (d, J = 8.8 Hz, 2H), 7.11 (d, J = 8.0 Hz,
2H), 6.92 (d, J = 8.4 Hz, 2H), 5.35 (s, 1H), 2.31 (s, 3H); 13C
NMR (100 MHz, CDCl3): δ 167.55, 153.20, 137.55, 134.23,
130.24, 129.92, 129.16, 128.16, 118.11, 115.01, 81.07, 20.67.
IR (KBr, cm−1): 2219 (νCuN). HRMS (EI) ([M]+) Calcd for
C16H12NOCl: 269.0607, Found: 269.0606.
(E)-3-(p-Tolyloxy)-non-2-enenitrile, 3r. Colorless oil. 1H
NMR (400 MHz, CDCl3): δ 7.20 (d, J = 8.4 Hz, 2H), 6.89–6.86
(m, 2H), 4.15 (s, 1H), 2.65 (t, J = 7.6 Hz, 2H), 2.36 (s, 3H),
1.79–1.72 (m, 2H), 1.47–1.42 (m, 2H), 1.38–1.33 (m, 4H), 0.93
(t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 178.96,
150.60, 136.02, 130.61, 120.75, 117.86, 74.17, 33.09, 31.37,
28.46, 26.84, 22.42, 20.76, 13.96. IR (KBr, cm−1): 2217
(νCuN). HRMS (EI) ([M]+) Calcd for C16H21NO: 243.1623,
(E)-3-(4-Methoxyphenyl)-3-(p-tolyloxy)acrylonitrile,
3p.
White solid, m.p. 54–56 °C. 1H NMR (400 MHz, CDCl3):
δ 7.97 (d, J = 8.8 Hz, 2H), 7.24 (d, J = 8.4 Hz, 2H), 7.01–6.99
(m, 4H), 4.45 (s, 1H), 3.88 (s, 3H), 2.39 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ 172.64, 161.98, 151.17, 135.95, 130.72,
129.72, 124.34, 120.83, 115.02, 113.83, 72.94, 55.38, 20.82. IR
(KBr, cm−1): 2212 (νCuN). HRMS (EI) ([M]+) Calcd for
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Found: 243.1626.
for C17H15NO: 249.1154, Found: 249.1158.
(Z)-3-(p-Tolyloxy)-non-2-enenitrile, 3r′. Colorless oil. 1H
NMR (400 MHz, CDCl3): δ 7.16 (d, J = 8.0 Hz, 2H), 6.95–6.92
(m, 2H), 4.67 (s, 1H), 2.35 (s, 3H), 2.23 (t, J = 7.6 Hz, 2H),
1.51–1.45 (m, 2H), 1.30–1.22 (m, 6H), 0.88 (t, J = 6.8 Hz, 3H);
13C NMR (100 MHz, CDCl3): δ 174.29, 151.62, 135.03,
130.08, 119.92, 115.19, 77.29, 32.94, 31.22, 28.32, 26.39,
22.30, 20.72, 13.87. IR (KBr, cm−1): 2220 (νCuN). HRMS (EI)
([M]+) Calcd for C16H21NO: 243.1623, Found: 243.1624.
2-Phenylbenzofuran-3-carbonitrile, 4a. White solid, m.p.
1
71–73 °C. H NMR (400 MHz, CDCl3): δ 8.20–8.18 (m, 2H),
7.72–7.70 (m, 1H), 7.58–7.50 (m, 4H), 7.44–7.36 (m, 2H); 13C
NMR (100 MHz, CDCl3): δ 161.57, 153.22, 131.13, 129.10,
127.72, 127.15, 126.40, 126.34, 124.63, 119.84, 114.25, 111.65,
88.01. IR (KBr, cm−1): 2222 (νCuN). HRMS (EI) ([M]+) Calcd
for C15H9NO: 219.0684, Found: 219.0687.
(E)-3-(p-Tolyloxy)-hept-2-enenitrile, 3s. Colorless oil. 1H
NMR (400 MHz, CDCl3): δ 7.20 (d, J = 7.6 Hz, 2H), 6.88 (d,
J = 7.6 Hz, 2H), 4.15 (s, 1H), 2.66 (t, J = 7.6 Hz, 2H), 2.36 (s,
3H), 1.78–1.71 (m, 2H), 1.53–1.44 (m, 2H), 1.00 (t, J = 7.6 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ 179.00, 150.63, 136.07,
130.64, 120.79, 117.91, 74.21, 32.87, 29.01, 22.02, 20.80,
13.75. IR (KBr, cm−1): 2217 (νCuN). HRMS (EI) ([M]+) Calcd
for C14H17NO: 215.1310, Found: 215.1307.
5-Methyl-2-phenylbenzofuran-3-carbonitrile, 4b. White solid,
m.p. 105–107 °C. 1H NMR (400 MHz, CDCl3): δ 8.19–8.17 (m,
2H), 7.56–7.49 (m, 4H), 7.45 (d, J = 8.4 Hz, 1H), 7.23–7.21 (m,
1H), 2.49 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 161.59,
151.75, 134.54, 131.01, 129.10, 127.94, 127.66, 127.28, 126.38,
119.61, 114.44, 111.18, 87.75, 21.31. IR (KBr, cm−1): 2222
(νCuN). HRMS (EI) ([M]+) Calcd for C16H11NO: 233.0841,
Found: 233.0844.
(Z)-3-(p-Tolyloxy)-hept-2-enenitrile, 3s′. Colorless oil. 1H
NMR (400 MHz, CDCl3): δ 7.17 (d, J = 8.0 Hz, 2H), 6.94 (d,
J = 8.0 Hz, 2H), 4.66 (s, 1H), 2.36 (s, 3H), 2.23 (t, J = 7.6 Hz,
2H), 1.52–1.45 (m, 2H), 1.34–1.27 (m, 2H), 0.88 (t, J = 7.2 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ 174.32, 151.64, 135.09,
130.12, 119.96, 115.23, 77.23, 32.73, 28.56, 21.85, 20.78,
13.60. IR (KBr, cm−1): 2220 (νCuN). HRMS (EI) ([M]+) Calcd
for C14H17NO: 215.1310, Found: 215.1311.
6-Methyl-2-phenylbenzofuran-3-carbonitrile, 4c. White solid,
m.p. 114–116 °C. 1H NMR (400 MHz, CDCl3): δ 8.16–8.14 (m,
2H), 7.55–7.51 (m, 4H), 7.34 (s, 1H), 7.18 (d, J = 7.6 Hz, 1H),
2.49 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 161.02, 153.64,
137.02, 130.88, 129.06, 127.92, 126.25, 126.04, 124.61, 119.29,
114.49, 111.77, 87.82, 21.74. IR (KBr, cm−1): 2225 (νCuN).
HRMS (EI) ([M]+) Calcd for C16H11NO: 233.0841, Found:
233.0842.
(Z)-3-(o-Tolyl)-3-(p-tolyloxy)acrylonitrile, 3t′. White solid,
1
m.p. 43–45 °C. H NMR (400 MHz, CDCl3): δ 7.37 (d, J = 7.2
7-Methyl-2-phenylbenzofuran-3-carbonitrile, 4d. White solid,
m.p. 82–83 °C. H NMR (400 MHz, CDCl3): δ 8.22–8.19 (m,
1
Hz, 1H), 7.29–7.26 (m, 1H), 7.21–7.17 (m, 1H), 7.12 (d, J = 7.2
Hz, 1H), 7.01 (d, J = 8.0 Hz, 2H), 6.85 (d, J = 8.0 Hz, 2H), 4.97
(s, 1H), 2.39 (s, 3H), 2.24 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ 170.45, 152.17, 136.24, 133.88, 132.19, 130.86,
130.48, 129.83, 129.72, 125.83, 118.70, 115.20, 82.88, 20.54,
20.10. IR (KBr, cm−1): 2212 (νCuN). HRMS (EI) ([M]+) Calcd
2H), 7.58–7.52 (m, 4H), 7.30–7.27 (m, 1H), 7.22–7.20 (m, 1H),
2.60 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 161.21, 152.33,
131.03, 129.09, 127.93, 127.29, 126.73, 126.38, 124.69, 122.08,
117.26, 114.48, 88.24, 14.81. IR (KBr, cm−1): 2220 (νCuN).
HRMS (EI) ([M]+) Calcd for C16H11NO: 233.0841, Found:
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233.0845.
([M]+) Calcd for C16H11NO2: 249.0790, Found: 249.0791.
5-Chloro-2-phenylbenzofuran-3-carbonitrile, 4i. White solid,
m.p. 108–110 °C. 1H NMR (400 MHz, CDCl3): δ 8.18–8.16 (m,
2H), 7.67 (d, J = 2.0 Hz, 1H), 7.56–7.54 (m, 3H), 7.51–7.49 (m,
1H), 7.39–7.36 (m, 1H); 13C NMR (100 MHz, CDCl3):
δ 162.86, 151.62, 131.61, 130.59, 129.23, 128.52, 127.31,
126.75, 126.56, 119.55, 113.61, 112.75, 87.66. IR (KBr, cm−1):
2224 (νCuN). HRMS (EI) ([M]+) Calcd for C15H8NOCl:
253.0294, Found: 253.0292.
5-Ethyl-2-phenylbenzofuran-3-carbonitrile, 4e. White solid,
m.p. 81–83 °C. H NMR (400 MHz, CDCl3): δ 8.20–8.18 (m,
1
2H), 7.57–7.47 (m, 5H), 7.27–7.24 (m, 1H), 2.80 (q, J = 7.6 Hz,
2H), 1.32 (t, J = 7.6 Hz, 3H); 13C NMR (100 MHz, CDCl3):
δ 161.66, 151.89, 141.10, 131.02, 129.12, 127.97, 127.32,
126.71, 126.39, 118.43, 114.51, 111.31, 87.91, 28.77, 15.99. IR
(KBr, cm−1): 2222 (νCuN). HRMS (EI) ([M]+) Calcd for
C17H13NO: 247.0997, Found: 247.0999.
5-Nitro-2-phenylbenzofuran-3-carbonitrile, 4j. White solid,
m.p. 152–153 °C. H NMR (400 MHz, CDCl3): δ 8.56 (d, J =
1
5-(iso-Propyl)-2-phenylbenzofuran-3-carbonitrile, 4f. White
solid, m.p. 64–66 °C. 1H NMR (400 MHz, CDCl3): δ 8.19–8.17
(m, 2H), 7.56–7.47 (m, 5H), 7.30–7.27 (m, 1H), 3.12–3.01 (m,
1H), 1.35 (s, 3H), 1.33 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 161.60, 151.85, 145.78, 130.96, 129.06, 127.91, 127.19,
126.32, 125.43, 116.89, 114.50, 111.28, 87.95, 34.08, 24.27. IR
(KBr, cm−1): 2224 (νCuN). HRMS (EI) ([M]+) Calcd for
C18H15NO: 261.1154, Found: 261.1151.
2.4 Hz, 1H), 8.33–8.31 (m, 1H), 8.18–8.15 (m, 2H), 7.70 (d, J =
9.2 Hz, 1H), 7.58–7.55 (m, 3H); 13C NMR (100 MHz, CDCl3):
δ 164.41, 155.55, 145.17, 132.28, 129.33, 127.67, 126.64,
126.46, 122.04, 116.17, 112.72, 112.31, 88.55. IR (KBr, cm−1):
2228 (νCuN). HRMS (EI) ([M]+) Calcd for C15H8N2O3:
264.0535, Found: 264.0538.
5-Benzoyl-2-phenylbenzofuran-3-carbonitrile,
4k. White
solid, m.p. 127–129 °C. 1H NMR (400 MHz, CDCl3):
δ 8.21–8.18 (m, 2H), 8.13 (d, J = 1.2 Hz, 1H), 7.96–7.94 (m,
1H), 7.83–7.81 (m, 2H), 7.68–7.62 (m, 2H), 7.57–7.51 (m, 5H);
13C NMR (100 MHz, CDCl3): δ 195.45, 163.02, 155.13,
137.31, 134.51, 132.59, 131.67, 129.89, 129.22, 128.56, 128.40,
127.15, 127.00, 126.53, 122.48, 113.60, 111.75, 88.42. IR (KBr,
cm−1): 2229 (νCuN), 1655 (νCvO). HRMS (EI) ([M]+) Calcd for
C22H13NO2: 323.0946, Found: 323.0952.
5-(tert-Butyl)-2-phenylbenzofuran-3-carbonitrile, 4g. White
solid, m.p. 55–57 °C. 1H NMR (400 MHz, CDCl3): δ 8.21–8.18
(m, 2H), 7.71–7.70 (m, 1H), 7.57–7.51 (m, 3H), 7.50–7.49 (m,
2H), 1.43 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 161.67,
151.58, 148.15, 130.98, 129.09, 127.96, 126.91, 126.35, 124.41,
116.08, 114.59, 111.00, 88.15, 34.93, 31.65. IR (KBr, cm−1):
2225 (νCuN). HRMS (EI) ([M]+) Calcd for C19H17NO:
275.1310, Found: 275.1307.
5-Methoxy-2-phenylbenzofuran-3-carbonitrile,
4h. White
4,6-Dimethyl-2-phenylbenzofuran-3-carbonitrile,
4l. White
solid, m.p. 113–115 °C. 1H NMR (400 MHz, CDCl3):
δ 8.16–8.14 (m, 2H), 7.55–7.50 (m, 3H), 7.44 (d, J = 9.2 Hz,
1H), 7.09 (d, J = 2.8 Hz, 1H), 7.00–6.97 (m, 1H), 3.88 (s, 3H);
13C NMR (100 MHz, CDCl3): δ 161.99, 157.26, 148.10,
131.00, 129.07, 127.92, 127.86, 126.27, 115.68, 114.42, 112.34,
101.40, 88.07, 55.85. IR (KBr, cm−1): 2225 (νCuN). HRMS (EI)
solid, m.p. 121–123 °C. 1H NMR (400 MHz, CDCl3):
δ 8.18–8.15 (m, 2H), 7.56–7.50 (m, 3H), 7.18 (s, 1H), 6.92 (s,
1H), 2.71 (s, 3H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ 161.12, 153.74, 136.78, 131.14, 130.73, 129.03, 128.12,
127.15, 126.27, 122.93, 115.98, 109.32, 87.31, 21.60, 17.79. IR
(KBr, cm−1): 2221 (νCuN). HRMS (EI) ([M]+) Calcd for
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C17H13NO: 247.0997, Found: 247.1001.
Found: 267.0452.
5-Chloro-6-methyl-2-phenylbenzofuran-3-carbonitrile, 4m.
1
White solid, m.p. 117–119 °C. H NMR (400 MHz, CDCl3):
2-Hexyl-5-methylbenzofuran-3-carbonitrile, 4r. Colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.40 (s, 1H), 7.36 (d, J = 8.4
Hz, 1H), 7.17–7.14 (m, 1H), 2.95 (t, J = 7.2 Hz, 2H), 2.47 (s,
3H), 1.86–1.78 (m, 2H), 1.42–1.32 (m, 6H), 0.91 (t, J = 6.8 Hz,
3H); 13C NMR (100 MHz, CDCl3): δ 168.70, 152.03, 134.07,
126.59, 125.99, 119.30, 113.58, 110.97, 90.26, 31.27, 28.64,
28.16, 27.40, 22.41, 21.24, 13.96. IR (KBr, cm−1): 2229
(νCuN). HRMS (EI) ([M]+) Calcd for C16H19NO: 241.1467,
Found: 241.1471.
δ 8.11–8.08 (m, 2H), 7.58 (s, 1H), 7.52–7.49 (m, 3H), 7.37 (s,
1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 161.92,
151.77, 134.81, 131.27, 131.07, 129.10, 127.37, 126.29, 126.07,
119.47, 113.73, 113.19, 87.22, 20.89. IR (KBr, cm−1): 2226
(νCuN). HRMS (EI) ([M]+) Calcd for C16H10NOCl: 267.0451,
Found: 267.0452.
2-Phenylnaphtho[1,2-b]furan-3-carbonitrile, 4n. White solid,
1
m.p. 142–144 °C. H NMR (400 MHz, CDCl3): δ 8.25 (d, J =
2-Butyl-5-methylbenzofuran-3-carbonitrile, 4s. Colorless oil.
1H NMR (400 MHz, CDCl3): δ 7.41 (s, 1H), 7.36 (d, J = 8.4
Hz, 1H), 7.16 (d, J = 8.4 Hz, 1H), 2.96 (t, J = 7.2 Hz, 2H), 2.47
(s, 3H), 1.84–1.77 (m, 2H), 1.48–1.39 (m, 2H), 0.97 (t, J = 7.6
Hz, 3H); 13C NMR (100 MHz, CDCl3): δ 168.73, 152.05,
134.12, 126.63, 126.00, 119.33, 113.65, 111.00, 90.29, 29.50,
27.90, 22.15, 21.28, 13.61. IR (KBr, cm−1): 2229 (νCuN).
HRMS (EI) ([M]+) Calcd for C14H15NO: 213.1154, Found:
213.1151.
8.4 Hz, 1H), 8.20–8.18 (m, 2H), 7.90 (d, J = 8.0 Hz, 1H), 7.72
(d, J = 8.4 Hz, 1H), 7.64–7.60 (m, 2H), 7.57–7.50 (m, 4H); 13C
NMR (100 MHz, CDCl3): δ 160.41, 148.92, 132.04, 130.73,
129.08, 128.51, 127.92, 127.13, 126.22, 126.01, 125.46, 123.13,
120.50, 119.74, 117.07, 114.31, 88.97. IR (KBr, cm−1): 2225
(νCuN). HRMS (EI) ([M]+) Calcd for C19H11NO: 269.0841,
Found: 269.0843.
Acknowledgements
This work was financially supported by the National Science
Foundation of China (Nos. 21172092 and 20102039).
2-(4-tert-Butylphenyl)-5-methylbenzofuran-3-carbonitrile, 4o.
White solid, m.p. 72–74 °C. 1H NMR (400 MHz, CDCl3):
δ 8.09 (d, J = 8.4 Hz, 2H), 7.55 (d, J = 8.4 Hz, 2H), 7.44 (s,
1H), 7.40 (d, J = 8.4 Hz, 1H), 7.17 (d, J = 8.4 Hz, 1H), 2.47 (s,
3H), 1.40 (s, 9H); 13C NMR (100 MHz, CDCl3): δ 161.70,
154.48, 151.48, 134.24, 127.26, 127.21, 126.08, 125.93, 125.02,
119.32, 114.47, 110.99, 86.89, 34.91, 30.97, 21.20. IR (KBr,
cm−1): 2221 (νCuN). HRMS (EI) ([M]+) Calcd for C20H19NO:
289.1467, Found: 289.1472.
Notes and references
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4 For Rosenmund–von Braun method, see: (a) K. W. Rosenmund and
E. Struck, Ber. Chem. Dtsch. Chem. Ges., 1919, 52, 1749; (b) J. von
Braun and G. Manz, Justus Liebigs Ann. Chem., 1931, 488, 111. For
Sandmeyer reaction, see: (c) T. Sandmeyer, Ber. Chem. Dtsch. Chem.
Ges., 1884, 17, 2650; (d) T. Sandmeyer, Ber. Chem. Dtsch. Chem. Ges.,
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5 Selected recent examples: Using KCN and NaCN as cyanation reagents,
(a) J. Zanon, A. Klapars and S. L. Buchwald, J. Am. Chem. Soc., 2003,
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2-(4-Chlorophenyl)-5-methylbenzofuran-3-carbonitrile,
4q.
1
White solid, m.p. 138–140 °C. H NMR (400 MHz, CDCl3):
δ 8.07–8.05 (m, 2H), 7.47–7.40 (m, 4H), 7.20 (d, J = 7.6 Hz,
1H), 2.47 (s, 3H); 13C NMR (100 MHz, CDCl3): δ 160.17,
151.65, 137.03, 134.69, 129.35, 127.90, 127.42, 127.02, 126.26,
119.58, 114.14, 111.15, 87.99, 21.29. IR (KBr, cm−1): 2223
(νCuN). HRMS (EI) ([M]+) Calcd for C16H10NOCl: 267.0451,
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