Synthesis of functionalized fluorescent indenes from electron-rich α-aryl ketonitriles

Article abstract of DOI:10.1021/jo300367q

A series of functionalized indenes bearing 1,3-dicyano groups were synthesized from electron-rich α-aryl ketonitriles in the presence of K₃Fe(CN)₆ and NaOAc, possibly through tandem process involving dimerization, heterolytic cleavag

Full text of DOI:10.1021/jo300367q

Article
pubs.acs.org/joc
Synthesis of Functionalized Fluorescent Indenes from Electron-Rich
α-Aryl Ketonitriles
Le Liu, Yanfeng Fan, Qiaoqiao He, Yun Zhang, Daisy Zhang-Negrerie, Jianhui Huang,* Yunfei Du,*
and Kang Zhao
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of Pharmaceutical Science and Technology, Tianjin
University, Tianjin 300072, China
S
* Supporting Information
ABSTRACT: A series of functionalized indenes bearing 1,3-
dicyano groups were synthesized from electron-rich α-aryl
ketonitriles in the presence of K3Fe(CN)6 and NaOAc,
possibly through tandem process involving dimerization,
heterolytic cleavage of carbon−carbon bond, intermolecular
coupling, and the subsequent intramolecular cyclization. The
2-arylindene compounds obtained possess good fluorescent
properties.
(Figure 1, path b).9 However, to the best of our knowledge, the
formation of indene compound directly from α-aryl ketonitriles
has not been reported before.
INTRODUCTION
■
Indenes show a wide range of biological activities1 and possess
great interest as functional materials as well as precursors for
catalysts of olefin polymerization.2 Consequently, recent years
have witnessed a number of reports on the construction of the
indene ring system. The most effective approaches for the
synthesis of indenes include the reduction or dehydration of
indanones,3 acid-catalyzed cyclodehydration of the phenyl-
substituted allylic alcohols,4 the ring expansion of certain
substituted cyclopropenes,5 and Lewis-acid catalyzed Friedel−
Crafts cyclization of aryl allenes.6 In addition to these classical
methods, transition metal7 catalyzed carboannulations of
alkynes have also been proven to be useful tools for the access
to indene rings. Each of these methods has its own merit in the
preparation of the corresponding indene compound with
specific substitution pattern. Herein, we described a novel
method that can afford a variety of highly functionalized
fluorescent indenes, which are undoubtedly difficult to achieve
by the existing approaches.
It has been well documented that the α-aryl ketonitriles can
undergo oxidative coupling reactions at benzylic position to
afford the diastereomeric homodimers in the presence of
various oxidants such as K3Fe(CN)6, KMnO4, Ag2O and PbO2
(Figure 1, path a).8 Alternatively, the electron-rich α-aryl
ketonitriles can also be converted into benzo[b]furan
compounds via intramolecular oxidative C−O bond formation
mediated by FeCl3, which acts as a single electron-oxidant
RESULTS AND DISCUSSION
■
Initially, we treated the electron-rich α,β-diaryl ketonitrile 1a
with K3Fe(CN)6, anticipating that the reaction would adopt the
“path a” depicted in Figure 1 to give the corresponding
homocoupled product. Unexpectedly, the reaction of 1a with
K3Fe(CN)6 in the presence of NaOAc in acetone under reflux
for 12 h was found to give the fluorescent compound 2a. The
result of X-ray crystal analysis clearly indicated that it is a novel
highly substituted indene compound (see the Supporting
Information for details).
Encouraged by this finding, 1a was used as a model substrate
to investigate the different parameters in order to optimize the
reaction conditions (Scheme 1). Screening of a series of other
solvents, including THF, 1,4-dioxane, DCE, EtOAc, MeCN,
EtOH, and DMF (Table 1, entries 2−8), showed that the
reaction in DCE at reflux afforded the best yield in 88% (Table
1, entry 4). Control experiment implied that the reaction
turned out to be sluggish if it was operated at room
temperature (Table 1, entry 9).
Furthermore, the base was found to be indispensable for the
conversion of 1a to 2a since no reaction occurred in the
absence of NaOAc (Table 1, entry 10). An examination of the
other bases revealed that Na2CO3 also provided a good yield of
2a, while the use of pyridine or triethylamine afforded the
product in much lower yield in each case. Finally, for
comparison we also carried out the reaction using other
iron(III) compounds. The results showed that no reaction
Received: February 21, 2012
Published: March 28, 2012
Figure 1. The existing oxidative reactions of α-aryl ketonitriles.
© 2012 American Chemical Society
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moderate to good yields. Furthermore, this method works
equally well for the substrates bearing the strong electron-
withdrawing trifluoromethyl group.
Scheme 1. Proposed Reaction Pathway
The substrate scope can be expanded with the β-phenyl ring
being changed with the thienyl, furyl, or pyridinyl rings.
Notably, when a vinyl group was inserted between the carbonyl
group and the aryl group in substrate 1a as a conjugation
bridge, the related ketonitrile 1p (not shown) was successfully
converted to indene 2p under the described conditions.
Intriguingly, when the β-aryl ring in the substrate was changed
to alkyl groups, the reactions also occurred to afford indene
products 2r and 2s in good yields of 68 and 78%, respectively.
Next, we turned to replace the α-phenyl ring with other
substituents. Substrates with only one methoxy group at either
para or meta position of the α-phenyl ring were also applicable
to give the corresponding indenes 2s and 2t, however in
relatively much lower yields. In addition, when the α-phenyl
ring was replaced with a methoxy substituted naphthyl ring, the
corresponding indene 2u can be obtained in a good 75% yield.
Furthermore, we found that methoxy group(s) on the α-
phenyl ring of the substrate is crucial for the reaction to occur.
The reaction failed for the α-phenylacetoacetonitrile (1v) and
α-phenylbenzoylacetonitrile (1w), in which the α-phenyl ring
bears no methoxy group. In both of these two cases, the
reactions adopt “path a” depicted in Figure 1 to give the
homodimerized products.
Table 1. Reaction Conditions Optimization for K3Fe(CN)6-
Mediated Synthesis of Indenes
A possible mechanistic pathway is proposed for this
heterocoupling/cyclization process (Scheme 1). On the basis
of the experimental fact that substrates without any methoxy
substituents on the α-phenyl ring will undergo homocoupling
at the benzylic position to give a dimer under the same
conditions, we postulated that the first step in the mechanistic
sequence might be the formation of the homodimer A, from
the benzylic radical intermediate (not shown) generated by the
single electron transfer process mediated by K3Fe(CN)6 in the
presence of base. Next, the electron-donating methoxy group in
the α-phenyl ring and the electron-withdrawing cyano and
carbonyl groups in intermediate A might exert the “push−pull”
effect, which leads to the heterolytic cleavage of the carbon−
carbon bond under thermal conditions to give the oxonium
intermediate B and enolate C. Subsequently, the conjugate
addition of enolate C to intermediate B affords the adduct D.
Further deprotonation from D realizes the rearomatization of
the phenyl ring and the formation of enolate E. The subsequent
intramolecular cyclization of E gives intermeidate F, which
undergoes further cyclization to form a four-membered ring
intermediate G. Finally, after the removal of one molecule of
benzoate anion, the title indene compound 2a can be achieved.
In all of the above reactions, the fragmented aryl carboxylic acid
(after acidic workup) can be detected by TLC comparison.
In order to test the possibility of the carbon−carbon bond
cleavage process described above, we came to subject the
homodimers 1a′, 1f′, and 1q′ to the identical reflux conditions
(Scheme 2). As expected, the corresponding indene products
can be formed in good yields. However, the homodimers of 1v
and 1w, without methoxy group on the α-phenyl ring, provided
no indene product at reflux in DCE even for 24 h, which
proved that the methoxy group substituted on the α-phenyl
ring played a vital role in the process.
a
b
entry
solvent
oxidant
base
yield (%)
1
acetone
THF
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
K3Fe(CN)6
Fe(NO3)3·9H2O
Fe(acac)3
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
NaOAc
38
30
59
88
56
41
2
3
dioxane
DCE
4
5
EtOAc
CH3CN
EtOH
DMF
DCE
6
ce
,
7
15
10
10
c
8
de
,
9
10
11
12
13
14
15
DCE
NR
82
DCE
Na2CO3
TEA
DCE
70
DCE
pyridine
NaOAc
NaOAc
50
e
e
DCE
NR
NR
DCE
a
Conditions: 1a (0.4 mmol), oxidant (3 equiv), and base (2 equiv)
reflux in solvent (4 mL) for 12 h. Isolated yields. Retarded by
unidentified byproducts. Carried out at rt, based on 30% conversion
of dimerized intermediate. The reaction time was prolonged to 24 h.
b
c
d
e
occurred when either Fe(acac)3 or hydrated Fe(NO3)3 was
applied.
Under the optimal reaction conditions, a series of substrates
bearing various substituents were employed to investigate the
scope of the method, and the results are summarized in Table
2. The reaction was found to tolerate a range of different
substituents on the β-phenyl ring in the substrates. When the
diaryl ketonitriles 1c−e (not shown) were substituted with
methoxy groups on the β-phenyl ring, they were converted into
the corresponding indene 2c−e in good to excellent 92, 90, and
80% yields, respectively. The substrates bearing halogen(s)
substituted at para, meta, or ortho position of the β-phenyl ring
also proceed successfully to afford the desired products 2f−j in
Furthermore, a preliminary survey of the optical properties of
this series of compounds was carried out. The photophysical
properties of some representative indenes are outlined in
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a
Table 2. Synthesis of Functionalized Indenes from Electron-Rich α-Aryl Ketonitriles
a
b
All the reactions were carried out with 1a (0.4 mmol), K3Fe(CN)6 (3 equiv), and Na2CO3 (2 equiv) reflux in DCE (4 mL) for 12 h. Isolated
yields.
Figure 2 and Table 3 (for the optical data of all the indenes 2,
see the Supporting Information).
HOMO−LUMO (highest occupied molecular orbital−lowest
unoccupied molecular orbital) gap and consequently pushes the
absorption and emission wavelengths, λabs and λem, respectively,
from the UV region to the visible region.10 The planar skeleton
of the indenes with a conjugated π-system enables them to
possess relatively larger Stokes shifts of around 84−130 nm,
with quantum yield ranging from 0.46 to 0.72.11
All target compounds listed in Table 2 exhibit fluorescence
property except for those where R2 is an alkyl group (2q, 2r,
and 2t). This indicates that π conjugation exists between the
unsaturated R2 substituent and the main π skeleton of the
indene, and it is this conjugation that significantly lowers the
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hypothesized that it might be ascribed to the π6 system of
Scheme 2. Evidence of the Carbon−Carbon Bond Cleavage
under the Thermal Conditions
5
thienyl ring, which is more electron-rich than the π66 system of
phenyl ring,13 and therefore decreases the energy gap of the
HOMO and LUMO.14
CONCLUSION
■
In conclusion, we have demonstrated a novel method to
synthesize functionalized indenes bearing 1,3-dicyano groups,
which features inexpensive reagents and mild reaction
conditions. Mechanistic study suggests that the reaction
involves an interesting tandem process involving dimerization,
heterolytic cleavage of carbon−carbon bond, intermolecular
coupling, and the subsequent intramolecuar cyclization.
EXPERIMENTAL SECTION
■
General Information. All reactions were carried out at room
temperature without precaution of air and stirred magnetically. 1H and
13C NMR spectra were recorded on a 400 MHz spectrometer at 25 °C.
Chemical shift values are given in ppm and referred as the internal
standard to TMS: 0.00 ppm. The peak patterns are indicated as
follows: s, singlet; d, doublet; t, triplet; q, quartet; qui, quintet; m,
multiplet, and dd, doublet of doublets. The coupling constants, J, are
reported in Hertz (Hz). High resolution mass spectrometry (HRMS)
was obtained on a Q-TOF microspectrometer. Melting points were
determined with MicroMelting point apparatus without corrections.
Organic solutions were concentrated by rotary evaporation below 40
°C in a vacuum. TLC plates were visualized by exposure to ultraviolet
light. Reagents and solvents were purchased as reagent grade and were
used without further purification. All reactions were performed in
standard glassware, heated at 110 °C for 3 h before use. Flash column
chromatography was performed over silica gel 100−200 m, and the
eluent was a mixture of ethyl acetate (EA) and petroleum ether (PE).
All the UV/vis spectra were performed on a spectrofluorimeter, and
fluorescent measurement was carried out on a fluorescent spectro-
fluorimeter with a concentration of 10 μM in CH2Cl2. The quantum
yields were measured using Rhodamine B as a standard (φ =
0.71).15−17
Figure 2. Absorption spectra (solid line) and fluorescence spectra
(dashed line) in CH2Cl2.
Table 3. Optical Data of Representative Indenes
λ
εmax
λ
Stokes shift
(cm−1
abs a
b
em a
c
indenes
(nm)
(M−1 cm−1
)
(nm)
)
φ
2a
2c
2l
375
363
390
404
408
361
7300
9000
506
498
523
519
518
461
91743
84746
0.68
0.55
0.55
0.52
0.48
0.46
8100
80000
Ketonitriles 1a−1u were prepared according to the literature.9,18
General Procedure for the Synthesis of Indenes (2a−2u). To
a solution of α-aryl ketonitriles 1 (0.4 mmol) in 1,2-dichloroethane (4
mL) were added potassium ferricyanide (0.395 g, 1.2 mmol) and
sodium acetate (0.066 g, 0.8 mmol) with efficient stirring at room
temperature. The mixture was then heated at reflux, and the process of
the reaction was monitored by TLC analysis. After the completion of
the reaction, the reaction mixture was filtered and washed with 1,2-
dichloroethane (15 mL × 3). The filtrate was concentrated in a
vacuum to remove the solvent. The residue was purified by silica gel
chromatography using a mixture of petroleum ether and ethyl acetate
as eluent to give the desired products 2.
2n
2p
2s
16800
21400
7200
95238
101010
119048
a
Wavelengths of maximum absorbance (λabs) or emission intensity
b
c
(λem). Extinction coefficient. Quantum yield determined by using
Rhodamine B as a standard (φ = 0.71).
Substituent effect on the energy gap of the HOMO and
LUMO affect the fluorescent properties of the indenes
dramatically. It is obvious that the introduction of an
electron-donating methoxy group to the α-phenyl ring, which
is known to increase the occupied molecular orbitals, leads to a
red-shift maximum comparing 2a with 2s as well as the increase
of quantum yield from 0.46 to 0.68. Substituents of the β ring
changing from methoxyl (2c) to trifluoromethyl (2l) and
thienyl group (2n) cause bathochromic emission wavelength
shifts from 498 to 523 and 519 nm. Relative to 2a, the
hypsochromic behavior in 2c is probably caused by reduced π
conjugation due to the steric effect of the bulky methoxyl group
on the β-phenyl ring. The red shift of 2p can be rationalized by
the more extended π system as a result of an extra CH
CH group. We suggested that the increase of both emission
wavelength and Stokes shift of 2l might be attributed to the
“push−pull” effect of the π-electron mode, in which the
methoxy groups act as electron donor and the electron-
withdrawing group (trifluoromethyl) of the indene acts as
electron acceptor.12 As to the bathochromic shift of 2n, we
2-(3,4-Dimethoxyphenyl)-3-oxo-3-(o-tolyl)propanenitrile
(1b). 1b was purified by silica gel chromatography (EA/PE = 15/85):
yield 2.235 g, 67%, isomers (enol/ketone ratio 5:1) are reported
together, white solid; 1H NMR (400 MHz, CDCl3) major isomer
(enol) δ 7.37 (d, J = 7.0 Hz, 1H), 7.32 (d, J = 7.0 Hz, 1H), 7.25−7.17
(m, 5H, peaks of two isomers overlapped), 6.88 (d, J = 8.0 Hz, 1H),
3.86 (s, 3H), 3.3.86 (s, 3H), 2.37 (s, 3H), minor isomer (ketone) δ
7.25−7.17 (m, 5H, peaks of two isomers overlapped), 6.64 (s, 2H),
6.24 (s, 1H), 3.76 (s, 3H), 3.39 (s, 3H), 2.12 (s, 3H); 13C NMR (100
MHz, CDCl3) major isomer (enol) δ 164.8, 149.3, 148.9, 136.4, 134.3,
130.8, 130.6, 129.0, 126.1, 123.8, 120.9, 119.1, 111.5, 111.0, 91.9, 56.0,
56.0, 19.4 (the 13C NMR data of the minor isomer was not collected
because of the low concentration); HRMS (ESI) m/z calcd for
+
C18H18NO3 [M + H]+ 296.1281, found 296.1283.
2-(3,4-Dimethoxyphenyl)-3-(3-methoxyphenyl)-3-oxopro-
panenitrile (1d). 1d was purified by silica gel chromatography (EA/
1
PE = 20/80): yield 2.710 g, 77%, white solid, mp 111−113 °C; H
NMR (400 MHz, CDCl3) δ 7.51 (d, J = 8.0 Hz, 1H), 7.45 (s, 1H),
7.33 (d, J = 8.0 Hz, 1H), 7.11 (dd, J = 8.0, 2.0 Hz, 1H), 6.97 (dd, J =
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8.0, 2.0 Hz, 1H), 6.90 (d, J = 2.0 Hz, 1H), 6.84 (d, J = 8.0 Hz, 1H),
5.58 (s, 1H), 3.85 (s, 3H), 3.84 (s, 3H), 3.81 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 189.0, 160.0, 149.9, 149.7, 135.0, 129.9, 122.6, 121.6,
121.1, 120.8, 116.8, 113.6, 111.8, 110.8, 56.1, 55.9, 55.5, 46.4; HRMS
(ESI) m/z calcd for C18H18NO4+ [M + H]+ 312.1230, found 312.1231.
(E)-3-(2,3-Dimethoxyphenyl)-2-(3,4-dimethoxyphenyl)-3-hy-
droxyacrylonitrile (1e). 1e was purified by silica gel chromatography
(EA/PE = 20/80): yield 2.735 g, 71%, white solid, mp 121−123 °C;
1H NMR (400 MHz, CDCl3) δ 7.98 (s, 1H), 7.41 (d, J = 7.0 Hz, 2H),
chromatography (EA/PE = 20/80): yield 2.245 g, 57%, white solid,
mp 129−131 °C; H NMR (400 MHz, CDCl3) δ 8.22 (s, 1H), 8.13
1
(d, J = 8.0 Hz, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.62 (t, J = 8.0 Hz, 1H),
6.99 (dd, J = 8.0, 2.0 Hz, 1H), 6.90 (d, J = 2.0 Hz, 1H), 6.88 (d, J = 8.0
Hz, 1H), 5.58 (s, 1H), 3.88 (s, 3H), 3.87 (s, 3H); 13C (100 MHz,
CDCl3) δ 187.9, 150.1, 150.0, 134.2, 132.2, 131.7 (d, JF−C = 33.2 Hz),
130.6 (d, JF−C = 3.3 Hz), 129.7, 126.0 (q, JF−C = 3.7 Hz), 123.3 (q,
JF−C = 271 Hz), 121.7, 121.0, 116.2, 112.0, 110.9, 56.1, 56.0, 46.8;
HRMS (ESI) m/z calcd for C18H15F3NO3+ [M + H]+ 350.0999, found
350.1003.
7.25 (d, J = 8.0 Hz, 1H), 7.11 (t, J = 8.0 Hz, 1H), 6.95−6.82 (m, 2H),
3.96−3.84 (m, 9H), 3.78 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
162.0, 152.5, 148.7, 148.5, 145.7, 129.0, 124.8, 124.7, 122.2, 121.2,
120.2, 114.5, 111.6, 111.1, 92.0, 61.7, 56.0, 55.9, 55.7; HRMS (ESI)
2-(3,4-Dimethoxyphenyl)-3-oxo-3-(4-(trifluoromethyl)-
phenyl)propanenitrile (1l). 1l was purified by silica gel chromatog-
raphy (EA/PE = 20/80): yield 2.640 g, 67%, white solid, mp 91−93
°C; 1H NMR (400 MHz, CDCl3) δ 8.02 (d, J = 8.0 Hz, 2H), 7.75 (d, J
= 8.0 Hz, 2H), 7.12 (dd, J = 8.0, 2.0 Hz, 1H), 7.03 (d, J = 2.0 Hz, 1H),
6.98 (d, J = 8.0 Hz, 1H), 6.56 (s, 1H), 3.93 (s, 6H); 13C NMR (100
MHz, CDCl3) δ 188.4, 150.0 (d, JF−C = 10.3 Hz), 136.4, 135.4 (q, JF−C
+
m/z calcd for C19H20NO5 [M + H]+ 342.1336, found 342.1338.
3-(2-Chlorophenyl)-2-(3,4-dimethoxyphenyl)-3-oxopropa-
nenitrile (1f). 1f was purified by silica gel chromatography (EA/PE =
20/80): yield 2.845 g, 68%, isomers (enol/ketone ratio 5:1) are
1
reported together, white solid; H NMR (400 MHz, CDCl3), major
= 32.8 Hz), 129. 6, 128.7, 126.0 (q, JF−C = 3.7 Hz), 123.2 (q, JF−C
=
isomer (enol), δ 7.57 (dd, J = 7.5, 2.0 Hz, 1H), 7.50 (dd, J = 7.5, 1.0
Hz, 1H), 7.44 (t, J = 7.5, 2.0 Hz, 1H), 7.41−7.35 (m, 1H), 7.30−7.28
(m, 1H), 7.24 (d, J = 2.0 Hz, 1H), 6.94 (d, J = 8.0 Hz, 1H), 6.74 (s,
1H), 3.93 (s, 3H), 3.92 (s, 3H), 3.81 (s, 1H), 3.56 (s, 1H), minor
isomer (ketone), 7.24 (d, J = 2.0 Hz, 2H), 7.21−7.18 (m, 2H), 6.68−
6.64 (m, 2H), 6.50 (s, 1H), 6.41 (d, J = 2.0 Hz, 1H), 3.79 (s, 3H), 3.54
(s, 3H); 13C NMR (100 MHz, CDCl3), major isomer, δ 161.8, 149.2,
149.0, 133.7, 132.8, 131.8, 130.9, 130.3, 127.1, 123.5, 121.1, 111.5,
111.4, 93.1, 56.1, 56.0, 49.7 (the 13C NMR data of the minor isomer
was not collected because of the low concentration); HRMS (ESI) m/
271 Hz), 121.7, 121.1, 116.4, 110.8, 56.1, 55.9, 46.8; HRMS (ESI) m/z
+
calcd for C18H15F3NO3 [M + H]+ 350.0999, found 350.1003.
2-(3,4-Dimethoxyphenyl)-3-oxo-3-(pyridin-4-yl)-
propanenitrile (1m). 1m was purified by silica gel chromatography
(EA/PE = 20/80): yield 1.910 g, 60%, yellow solid, mp 221−223 °C;
1H NMR (400 MHz, CDCl3) δ 8.78 (d, J = 6.0 Hz, 1H), 8.48 (d, J =
6.0 Hz, 1H), 7.76 (d, J = 6.0 Hz, 1H), 7.71−7.65 (m, 1H), 7.31 (d, J =
8.0 Hz, 1H), 6.95 (dd, J = 8.0, 2.0 Hz, 1H), 6.86 (d, J = 8.0, 1H), 5.45
(s, 1H), 3.92 (s, 3H), 3.87 (s, 3H); 13C NMR (100 MHz, DMSO-d6)
δ 164.3, 150.2, 148.8, 148.5, 143.8, 125.3, 123.8, 123.4, 120.8, 112.2,
111.8, 89.7, 56.0, 55.9; HRMS (ESI) m/z calcd for C16H15N2O3+ [M +
H]+ 283.1077, found 283.1078.
2-(3,4-Dimethoxyphenyl)-3-(furan-2-yl)-3-oxopropanenitrile
(1o). 1o was purified by silica gel chromatography (EA/PE = 15/85):
yield 1.745 g, 57%, white solid, mp 98−100 °C; 1H NMR (400 MHz,
CDCl3) δ 7.64 (s, 1H), 7.36 (d, J = 3.5 Hz, 1H), 7.02 (dd, J = 8.0, 2.0
Hz, 1H), 6.96 (d, J = 2.0 Hz, 1H), 6.85 (d, J = 8.0 Hz, 1H), 6.65−6.49
(m, 1H), 5.41 (s, 1H), 3.88 (s, 3H), 3.86 (s,3H); 13C NMR (100
MHz, CDCl3) δ 177.6, 149.8, 149.7, 147.8, 122.1, 121.2, 120.4, 116.4,
113.4, 111.7, 111.1, 56.1, 55.9, 46.0 (one carbon peak was missing
because of overlapping); HRMS (ESI) m/z calcd for C15H14NO4+ [M
+ H]+ 272.0917, found 272.0919.
(E)-2-(3,4-Dimethoxyphenyl)-3-oxo-5-phenylpent-4-eneni-
trile (1p). 1p was purified by silica gel chromatography (EA/PE = 20/
80): yield 2.080 g, 60%, yellow solid, mp 149−151 °C; 1H NMR (400
MHz, CDCl3) δ 7.57 (d, J = 7.0 Hz, 2H), 7.45−7.37 (m, 3H), 7.35 (d,
J = 6.0 Hz, 1H), 7.18 (d, J = 16.0 Hz, 1H), 7.05 (dd, J = 8.0, 2.0 Hz,
1H), 6.98 (d, J = 2.0 Hz, 1H), 6.95 (d, J = 8.0 Hz, 1H), 6.28 (s, 1H),
3.92 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 189.6, 161.0, 146.9,
136.6, 131.5, 129.1, 127.7, 123.2, 120.3, 119.0, 116.6, 112.0, 111.6,
110.7, 56.1, 56.0, 49.7; HRMS (ESI) m/z calcd for C19H18NO3+ [M +
H]+ 308.1281, found 308.1281.
+
z calcd for C17H1535ClNO3 [M + H]+ 316.0735, found 316.0739.
3-(4-Chlorophenyl)-2-(3,4-dimethoxyphenyl)-3-oxopropa-
nenitrile (1g). 1g was purified by silica gel chromatography (EA/PE
= 25/75): yield 2.970 g, 72%, white solid, mp 105−107 °C; 1H NMR
(400 MHz, CDCl3) δ 7.88 (d, J = 8.5 Hz, 2H), 7.42 (d, J = 8.5 Hz,
2H), 6.95 (dd, J = 8.0, 2.0 Hz, 1H), 6.88−6.85 (m, 2H), 5.50 (s, 1H),
3.86 (s, 3H), 3.85 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 188.1,
149.9, 149.8, 141.0, 132.0, 130.6, 129.3, 122.2, 121.0, 116.6, 111.9,
+
110.8, 56.1, 55.9, 46.5; HRMS (ESI) m/z calcd for C17H1535ClNO3
[M + H]+ 316.0735, found 316.0739.
3-(3-Bromophenyl)-2-(3,4-dimethoxyphenyl)-3-oxopropa-
nenitrile (1h). 1h was purified by silica gel chromatography (EA/PE
= 20/80): yield 3.160 g, 78%, white solid, mp 151−153 °C; 1H NMR
(400 MHz, CDCl3) δ 8.07 (s, 1H), 7.85 (d, J = 8.0 Hz, 1H), 7.70 (d, J
= 8.0 Hz, 1H), 7.33 (t, J = 8.0 Hz, 1H), 6.95 (dd, J = 8.0, 2.0 Hz, 1H),
6.88 (d, J = 2.0 Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H) 5.51 (s, 1H), 3.87 (s,
3H), 3.86 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 187.9, 150.0,
149.9, 137.2, 135.4, 132.2, 130.5, 127.6, 123.3, 121.9, 121.1, 116.4,
111.9, 110.8, 56.1, 56.0, 46.5; HRMS (ESI) m/z calcd for
+
C17H1579BrNO3 [M + H]+ 360.0230, found 360.0233.
2-(3,4-Dimethoxyphenyl)-3-(4-fluorophenyl)-3-oxopropane-
nitrile (1i). 1i was purified by silica gel chromatography (EA/PE =
1
25/75): yield 2.165 g, 64%, white solid, mp 102−104 °C; H NMR
2-(7-Methoxynaphthalen-1-yl)-3-oxo-3-phenylpropaneni-
(400 MHz, CDCl3) δ 8.03−7.94 (m, 2H), 7.11 (t, J = 8.5 Hz, 2H),
6.97 (dd, J = 8.0, 2.0 Hz, 1H), 6.90 (d, J = 2.0 Hz, 1H), 6.85 (d, J = 8.0
Hz, 1H), 5.59 (s, 1H), 3.85 (s, 6H); 13C NMR (100 MHz, CDCl3) δ
187.8, 166.2 (d, JF−C = 256 Hz), 149.9, 149.8, 132.0 (d, JF−C = 10 Hz),
130.1, 122.4, 121.0, 116.2 (d, JF−C = 22 Hz), 116.1, 111.9, 110.9, 56.1,
trile (1u). 1u was purified by silica gel chromatography (EA/PE = 15/
1
85): yield 0.855 g, 55%, white solid, mp 131−133 °C; H NMR (400
MHz, CDCl3) δ 7.91 (d, J = 7.5 Hz, 2H), 7.78 (d, J = 9.0 Hz, 2H),
7.58 (d, J = 7.0 Hz, 1H), 7.52 (t, J = 7.0 Hz, 1H), 7.37 (t, J = 8.0 Hz,
2H), 7.32 (d, J = 7.5 Hz, 1H), 7.30−7.26 (m, 1H), 7.20 (dd, J = 9.0,
2.0 Hz, 1H), 6.13 (s, 1H), 3.90 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ 189.6, 159.0, 134.3, 134.1, 131.7, 130.9, 129.9, 129.7, 129.1, 129.0,
128.6, 125.2, 123.3, 119.1, 116.2, 101.5, 55.5, 45.3; HRMS (ESI) m/z
+
55.9, 46.4; HRMS (ESI) m/z calcd for C17H15FNO3 [M + H]+
300.1030, found 300.1030.
(E)-3-(3,4-Dichlorophenyl)-2-(3,4-dimethoxyphenyl)-3-hy-
droxyacrylonitrile (1j). 1j was purified by silica gel chromatography
(EA/PE = 20/80): yield 2.955 g, 75%, yellow solid, mp 133−135 °C;
1H NMR (400 MHz, CDCl3) δ 7.96 (d, J = 2.0 Hz, 1H), 7.80 (dd, J =
+
calcd for C20H16NO2 [M + H]+ 302.1176, found 302.1178.
1-(3,4-Dimethoxyphenyl)-5,6-dimethoxy-2-phenyl-1H-in-
dene-1,3-dicarbonitrile (2a). 2a was purified by silica gel
chromatography (EA/PE = 15/85): yield 0.077 g, 88%, yellow green
solid, mp 163−165 °C; 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 8.0
Hz, 2H), 7.40 (d, J = 8.0 Hz, 2H), 7.14 (s, 1H), 6.99 (d, J = 8.0 Hz,
2H), 6.84−6.80 (m, 2H), 6.62 (s, 1H), 4.02 (s, 3H), 3.88 (s, 3H), 3.87
(s, 3H), 3.76 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.3, 151.3,
151.0, 150.2, 149.9, 137.4, 131.1, 130.8, 129.4, 128.3, 126.2, 118.9,
118.5, 115.1, 113.2, 112.1, 108.8, 108.8, 107.3, 104.2, 57.5, 56.8, 56.8,
8.0, 2.0 Hz, 1H), 7.56 (d, J = 8.0 Hz, 1H), 7.09 (dd, J = 8.0, 2.0 Hz,
1H), 7.00 (d, J = 2.0 Hz, 1H), 6.96 (d, J = 8.0 Hz, 1H), 6.55 (s, 1H),
3.92 (s, 3H), 3.92 (s, 3H); 13C NMR (100 MHz, DMSO-d6) δ 164.0,
148.8, 148.6, 136.6, 133.5, 131.7, 131.1, 131.0, 129.9, 129.5, 125.4,
122.4, 120.9, 112.3, 112.1, 89.9, 56.0; HRMS (ESI) m/z calcd for
35
+
C17H14 Cl2NO3 [M + H]+ 350.0345, found 350.0349.
2-(3,4-Dimethoxyphenyl)-3-oxo-3-(3-(trifluoromethyl)-
phenyl)propanenitrile (1k). 1k was purified by silica gel
4001
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The Journal of Organic Chemistry
Article
+
56.4, 56.3; HRMS (ESI) m/z calcd for C27H26N3O4 [M + NH4]+
456.1918, found 456.1917.
56.6, 56.4; HRMS (ESI) m/z calcd for C27H2535ClN3O4+ [M + NH4]+
490.1528, found 490.1526.
1-(3,4-Dimethoxyphenyl)-5,6-dimethoxy-2-o-tolyl-1H-in-
dene-1,3-dicarbonitrile (2b). 2b was purified by silica gel
chromatography (EA/PE = 15/85): yield 0.063 g, 69%, white solid,
2-(3-Bromophenyl)-1-(3,4-dimethoxyphenyl)-5,6-dime-
thoxy-1H-indene-1,3-dicarbonitrile (2h). 2h was purified by silica
gel chromatography (EA/PE = 15/85): yield 0.094 g, 91%, yellow
green solid, mp 189−191 °C; 1H NMR (400 MHz, CDCl3) δ 7.83 (s,
1H), 7.60 (d, J = 8.0 Hz, 1H), 7.53 (d, J = 8.0 Hz, 1H), 7.24 (d, J = 8.0
Hz, 1H), 7.13 (s, 1H), 6.92 (dd, J = 8.0, 2.0 Hz, 1H), 6.88−6.76 (m,
2H), 6.59 (d, J = 2.0 Hz, 1H), 4.01 (s, 3H), 3.87 (s, 6H), 3.76 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 154.6, 151.6, 151.5, 150.4, 150.3,
1
mp 184−186 °C; H NMR (400 MHz, CDCl3) δ 7.31 (t, J = 7.5 Hz,
1H), 7.21 (d, J = 7.5 Hz, 1H), 7.14 (s, 2H), 7.02 (s, 2H), 6.73 (d, J =
8.0 Hz, 1H), 6.56 (d, J = 8.0 Hz, 1H), 6.41 (s, 1H), 4.03 (s, 3H), 3.91
(s, 3H), 3.86 (s, 3H), 3.59 (s, 3H), 1.98 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 158.0, 151.1, 150.5, 149.9, 149.3, 137.6, 134.7, 131.4, 130.6,
129.9, 129.8, 128.7, 125.5, 124.3, 119.2, 117.7, 116.0, 113.5, 111.2,
110.3, 107.9, 104.0, 59.0, 56.5, 56.5, 55.9, 55.8, 19.2; HRMS (ESI) m/z
137.6, 134.0, 132.9, 131.1, 131.0, 130.9, 127.0, 125.6, 123.6, 119.1,
118.2, 114.6, 114.6, 112.4, 109.1, 107.4, 104.4, 57.7, 57.0, 56.9, 56.6,
+
calcd for C28H28N3O4 [M + NH4]+ 470.2074, found 470.2070.
+
56.4; HRMS (ESI) m/z calcd for C27H2579BrN3O4 [M + NH4]+
1-(3,4-Dimethoxyphenyl)-5,6-dimethoxy-2-(2-methoxy-
phenyl)-1H-indene-1,3-dicarbonitrile (2c). 2c was purified by
silica gel chromatography (EA/PE = 15/85): yield 0.086 g, 92%,
yellow green solid, mp 129−131 °C; H NMR (400 MHz, CDCl3) δ
534.1023, found 534.1023.
1-(3,4-Dimethoxyphenyl)-2-(4-fluorophenyl)-5,6-dime-
thoxy-1H-indene-1,3-dicarbonitrile (2i). 2i was purified by silica
gel chromatography (EA/PE = 20/80): yield 0.061 g, 67%, yellow
green solid, mp 109−111 °C; H NMR (400 MHz, CDCl3) δ 7.77−
7.67 (m, 2H), 7.13 (s, 1H), 7.08 (t, J = 8.5 Hz, 2H), 6.98 (dd, J = 8.5,
2.0 Hz, 1H), 6.84 (d, J = 7.5 Hz, 2H), 6.59 (d, J = 2.0 Hz, 1H), 4.01 (s,
3H), 3.87 (s, 6H), 3.76 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 163.8
(d, JF−C = 252 Hz), 154.7, 151.0, 150.8, 149.9, 149.7, 136.87, 130.6,
130.1 (d, JF−C = 8.4 Hz), 126.7 (d, JF−C = 3.3 Hz), 125.6, 118.5, 117.9,
116.3 (d, JF−C = 21.8 Hz), 114.6, 112.9, 111.9, 108.4, 107.0, 103.9,
1
1
7.35 (t, J = 7.5 Hz, 1H), 7.29 (d, J = 7.5 Hz, 1H), 7.14 (s, 1H), 6.94 (d,
J = 8.5 Hz, 2H), 6.91−6.86 (m, 2H), 6.77 (d, J = 8.5 Hz, 1H), 6.51 (s,
1H), 4.01 (s, 3H), 3.88 (s, 3H), 3.84 (s, 3H), 3.82 (s, 3H), 3.69 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 157.4, 153.5, 151.1, 150.6,
149.7, 149.6, 136.7, 131.9, 131.5, 129.5, 125.6, 120.7, 120.2, 119.2,
118.3, 117.2, 114.2, 111.7, 111.5, 109.3, 107.6, 104.1, 58.6, 56.6, 56.1,
55.4 (two OMe carbon peaks were missing because of overlapping);
+
HRMS (ESI) m/z calcd for C28H28N3O5 [M + NH4]+ 486.2023,
+
57.3, 56.4, 56.4, 56.1, 55.9; HRMS (ESI) m/z calcd for C27H25FN3O4
[M + NH4]+ 474.1824, found 474.1823.
found 486.2020.
1-(3,4-Dimethoxyphenyl)-5,6-dimethoxy-2-(3-methoxy-
phenyl)-1H-indene-1,3-dicarbonitrile (2d). 2d was purified by
silica gel chromatography (EA/PE = 20/80): yield 0.084 g, 90%,
2-(3,4-Dichlorophenyl)-1-(3,4-dimethoxyphenyl)-5,6-dime-
thoxy-1H-indene-1,3-dicarbonitrile (2j). 2j was purified by silica
gel chromatography (EA/PE = 20/80): yield 0.083 g, 82%, yellow
green solid, mp 153−157 °C; 1H NMR (400 MHz, CDCl3) δ 7.80 (d,
J = 2.0 Hz, 1H), 7.53 (dd, J = 8.5, 2.0 Hz, 1H), 7.45 (d, J = 8.5 Hz,
1H), 7.12 (s, 1H), 6.93 (dd, J = 8.5, 2.0 Hz, 1H), 6.83 (t, J = 5.0 Hz,
2H), 6.57 (d, J = 2.0 Hz, 1H), 4.00 (s, 3H), 3.87 (s, 6H), 3.76 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 187.5, 152.9, 151.2, 151.1, 150.0,
1
yellow green solid, mp 170−172 °C; H NMR (400 MHz, CDCl3) δ
7.36−7.28 (m, 3H), 7.14 (s, 1H), 7.00 (d, J = 9.5 Hz, 1H), 6.95 (d, J =
5.5 Hz, 1H), 6.84 (d, J = 9.0 Hz, 2H), 6.62 (s, 1H), 4.02 (s, 3H), 3.87
(s, 6H), 3.78 (s, 6H); 13C NMR (100 MHz, CDCl3) δ 159.7, 155.8,
151.0, 150.8, 149.9, 149.7, 137.1, 131.6, 130.7, 130.0, 126.0, 120.4,
118.5, 118.1, 117.0, 114.7, 113.0, 112.9, 111.9, 108.7, 107.0, 103.9,
57.2, 56.4, 56.1, 55.9, 55.4 (one carbon peak was missing because of
149.9, 137.2, 135.0, 133.5, 131.1, 130.2, 129.4, 127.0, 124.9, 118.5,
117.6, 114.3, 114.1, 111.9, 108.3, 106.8, 103.9, 57.1, 56.5, 56.4, 56.1,
+
overlapping); HRMS (ESI) m/z calcd for C28H28N3O5 [M + NH4]+
+
55.9; HRMS (ESI) m/z calcd for C27H2435Cl2N3O4 [M + NH4]+
486.2023, found 486.2020.
524.1138, found 524.1135.
2-(2,3-Dimethoxyphenyl)-1-(3,4-dimethoxyphenyl)-5,6-di-
methoxy-1H-indene-1,3-dicarbonitrile (2e). 2e was purified by
silica gel chromatography (EA/PE = 20/80): yield 0.080 g, 80%,
yellow green solid, mp 128−130 °C; H NMR (400 MHz, CDCl3) δ
1-(3, 4-Dimethoxyphenyl) -5, 6-dimethoxy-2-(3-
(trifluoromethyl)phenyl)-1H-indene-1,3-dicarbonitrile (2k). 2k
was purified by silica gel chromatography (EA/PE = 25/75): yield
0.085 g, 84%, yellow green solid, mp 219−221 °C; H NMR (400
1
1
7.16 (s, 1H), 7.03−6.91 (m, 3H), 6.82−6.72 (m, 3H), 6.58 (s, 1H),
4.03 (s, 3H), 3.90 (s, 3H), 3.86 (s, 6H), 3.70 (s, 3H), 3.66 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 154.2, 153.3, 151.5, 151.0, 150.1, 149.9,
148.2, 136.6, 132.0, 125.6, 125.3, 123.9, 121.4, 119.6, 118.6, 117.5,
115.2, 114.3, 111.8, 110.3, 108.0, 104.5, 61.6, 59.0, 56.9, 56.9, 56.4,
MHz, CDCl3) δ 7.91 (s, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.0
Hz, 1H), 7.52 (t, J = 8.0 Hz, 1H), 7.14 (s, 1H), 6.92 (dd, J = 8.0, 2.0
Hz, 1H), 6.86 (s, 1H), 6.82 (d, J = 8.0 Hz, 1H), 6.60 (d, J = 2.0 Hz,
1H), 4.01 (s, 3H), 3.87 (s, 3H), 3.86 (s, 3H), 3.75 (s, 3H); 13C NMR
(100 MHz, CDCl3) δ 154.0, 151.2, 151.2, 150.0 (d, JF−C = 9.7 Hz),
137.2, 131.9, 131.8 (q, JF−C = 32.7 Hz), 131.2, 131.1, 130.4, 129.7,
127.0, 124.9, 124.5 (q, JF−C = 3.6 Hz), 123.5 (q, JF−C = 271 Hz), 118.6,
117.6, 114.5, 114.1, 112.0, 108.6, 107.0, 104.0, 57.3, 56.4, 56.4, 56.1,
+
56.4, 56.3; HRMS (ESI) m/z calcd for C29H30N3O6 [M + NH4]+
516.2129, found 516.2126.
2-(2-Chlorophenyl)-1-(3,4-dimethoxyphenyl)-5,6-dime-
thoxy-1H-indene-1,3-dicarbonitrile (2f). 2f was purified by silica
gel chromatography (EA/PE = 15/85): yield 0.065 g, 69%, yellow
green solid, mp 129−131 °C; 1H NMR (400 MHz, CDCl3) δ 7.45 (d,
J = 8.0 Hz, 1H), 7.37 (t, J = 8.0 Hz, 1H), 7.28−7.20 (m, 2H), 7.18 (s,
1H), 6.98 (s, 1H), 6.81−6.71 (m, 2H), 6.46 (s, 1H), 4.05 (s, 3H), 3.91
(s, 3H), 3.87 (s, 3H), 3.67 (s, 3H); 13C NMR (100 MHz, CDCl3) δ
153.8, 151.1, 150.9, 149.9, 149.4, 135.6, 134.3, 131.2, 131.0, 130.3,
130.0, 129.5, 126.6, 123.7, 119.5, 118.2, 117.4, 113.2, 111.3, 109.8,
107.6, 104.2, 58.8, 56.5, 55.9, 55.9 (one OMe carbon peak was missing
+
55.9; HRMS (ESI) m/z calcd for C28H25F3N3O4 [M + NH4]+
524.1792, found 524.1790.
1-(3, 4-Dimethoxyphenyl) -5, 6-dimethoxy-2-(4-
(trifluoromethyl)phenyl)-1H-indene-1,3-dicarbonitrile (2l). 2l
was purified by silica gel chromatography (EA/PE = 20/80): yield
1
0.082 g, 81%, yellow green solid, mp 219−221 °C; H NMR (400
MHz, CDCl3) δ 7.92 (s, 1H), 7.86 (d, J = 8.0 Hz, 1H), 7.65 (d, J = 8.0
Hz, 1H), 7.53 (t, J = 8.0 Hz, 1H), 7.15 (s, 1H), 6.93 (dd, J = 8.0, 2.0
Hz, 1H), 6.88−6.80 (m, 2H), 6.60 (d, J = 2.0 Hz, 1H), 4.02 (s, 3H),
3.88 (s, 3H), 3.86 (s, 3H), 3.75 (s, 3H); 13C NMR (100 MHz, CDCl3)
δ153.9, 151.3, 151.2, 150.0, 149.9, 137.3, 133.8, 132.0 (q, JF−C = 32.7
Hz), 130.3, 128.2, 126.0 (q, JF−C = 3.7 Hz), 125.0, 123.5 (q, JF−C = 271
Hz), 118.6, 117.7, 114.9, 114.1, 111.9, 108.4, 106.9, 104.1, 57.3, 56.5,
+
because of overlapping); HRMS (ESI) m/z calcd for C27H2535ClN3O4
[M + NH4]+ 490.1528, found 490.1526.
2-(4-Chlorophenyl)-1-(3,4-dimethoxyphenyl)-5,6-dime-
thoxy-1H-indene-1,3-dicarbonitrile (2g). 2g was purified by silica
gel chromatography (EA/PE = 20/80): yield 0.081 g, 86%, yellow
green solid, mp 121−124 °C; 1H NMR (400 MHz, CDCl3) δ 7.68 (d,
J = 8.0 Hz, 2H), 7.37 (d, J = 8.0 Hz, 2H), 7.29 (s, 1H), 6.98 (d, J = 8.0
Hz, 1H), 6.84 (d, J = 8.0 Hz, 2H), 6.59 (s, 1H), 4.02 (s, 3H), 3.88 (s,
6H), 3.77 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 154.9, 151.5,
151.4, 150.4, 150.2, 137.5, 137.3, 130.9, 129.9, 129.6, 129.3, 125.9,
119.0, 118.4, 115.0, 113.7, 112.3, 108.8, 107.4, 104.3, 57.6, 56.9, 56.9,
+
56.4, 56.1, 55.9; HRMS (ESI) m/z calcd for C28H25F3N3O4 [M +
NH4]+ 524.1792, found 524.1790.
1-(3,4-Dimethoxyphenyl)-5,6-dimethoxy-2-(pyridin-4-yl)-
1H-indene-1,3-dicarbonitrile (2m). 2m was purified by silica gel
chromatography (EA/PE = 20/80): yield 0.072 g, 82%, yellow green
solid, mp 205−207 °C; 1H NMR (400 MHz, CDCl3) δ 8.67 (d, J = 5.0
Hz, 2H), 7.58 (d, J = 5.0 Hz, 2H), 7.16 (s, 1H), 6.97 (d, J = 7.0 Hz,
4002
dx.doi.org/10.1021/jo300367q | J. Org. Chem. 2012, 77, 3997−4004

The Journal of Organic Chemistry
Article
1H), 6.90−6.80 (m, 2H), 6.58 (s, 1H), 4.01 (s, 3H), 3.88 (s, 3H), 3.87
(s, 3H) 3.76 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 152.2, 151.6,
151.2, 150.7, 150.0, 149.9, 137.7, 137.3, 130.0, 124.7, 121.2, 118.5,
117.5, 116.1, 113.8, 112.0, 108.2, 106.8, 104.1, 56.8, 56.5, 56.4, 56.1,
55.9; HRMS (ESI) m/z calcd for C26H22N3O4+ [M + NH4]+ 440.1605,
found 440.1606.
1-(3,4-Dimethoxyphenyl)-5,6-dimethoxy-2-(thiophen-2-yl)-
1H-indene-1,3-dicarbonitrile (2n). 2n was purified by silica gel
chromatography (EA/PE = 20/80): yield 0.072 g, 81%, yellow green
solid, mp 191−193 °C; 1H NMR (400 MHz, CDCl3) δ 7.60 (d, J = 3.0
Hz, 1H), 7.48 (d, J = 5.0 Hz, 1H), 7.13−7.02 (m, 3H), 6.88 (d, J = 8.0
Hz, 1H), 6.80 (s, 1H), 6.67 (s, 1H), 4.00 (s, 3H), 3.89 (s, 3H), 3.86 (s,
3H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 151.0, 150.5,
149.9, 149.8, 149.7, 136.5, 133.2, 130.6, 130.3, 129.9, 128.0, 126.1,
118.8, 118.0, 114.8, 111.8, 109.1, 108.6, 106.9, 103.7, 57.3, 56.4, 56.4,
56.1, 55.9; HRMS (ESI) m/z calcd for C25H21N2O4S [M + NH4]+
445.1217, found 445.1219.
110.2, 56.9, 55.8, 55.3; HRMS (ESI) m/z calcd for C25H22N3O2+ [M +
NH4]+ 396.1707, found 396.1703.
5-Methoxy-1-(3-methoxyphenyl)-2-methyl-1H-indene-1,3-
dicarbonitrile (2t). 2t was purified by silica gel chromatography (EA/
1
PE = 15/75): yield 0.037 g, 58%, colorless oil; H NMR (400 MHz,
CDCl3) δ 7.29 (d, J = 8.0 Hz, 1H), 7.23 (d, J = 8.0 Hz, 1H), 7.04 (d, J
= 2.0 Hz, 1H), 6.92−6.82 (m, 2H), 6.77 (d, J = 8.0 Hz, 1H), 6.70 (s,
1H), 3.87 (s, 3H), 3.77 (s, 3H), 2.20 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 161.3, 161.1, 160.4, 139.9, 135.1, 134.6, 130.7, 125.2, 118.0,
117.0, 115.0, 114.6, 114.0, 113.1, 112.2, 106.1, 57.7, 55.8, 55.4, 13.6;
+
HRMS (ESI) m/z calcd for C20H20N3O2 [M + NH4]+ 334.1550,
found 334.1550.
8-Methoxy-3-(7-methoxynaphthalen-1-yl)-2-phenyl-3H-
cyclopenta[a]naphthalene-1,3-dicarbonitrile (2u). 2u was puri-
fied by silica gel chromatography (EA/PE = 20/80): yield 0.072 g,
75%, yellow green solid, mp 205−207 °C; 1H NMR (400 MHz,
CDCl3) δ 8.49 (s, 1H), 8.43 (d, J = 7.5 Hz, 1H), 7.85 (d, J = 9.0 Hz,
2H), 7.78 (d, J = 8.0 Hz, 1H), 7.68 (d, J = 9.0 Hz, 1H), 7.64 (d, J = 7.5
Hz, 2H), 7.51 (t, J = 8.0 Hz, 1H), 7.42−7.29 (m, 4H), 7.20 (d, J = 8.0
Hz, 1H), 6.98 (d, J = 9.0 Hz, 1H), 6.27 (s, 1H), 4.09 (s, 3H), 3.25 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 160.1, 159.7, 158.3, 143.0,
132.0, 131.0, 130.8, 130.7, 130.6, 130.5, 129.8, 129.7, 129.5, 129.2,
129.0, 128.2, 126.1, 123.2, 120.4, 119.2, 118.3, 117.6, 117.1, 112.7,
101.0, 100.8, 60.6, 55.7, 54.7 (two carbon were missing because of
1-(3,4-Dimethoxyphenyl)-2-(furan-2-yl)-5,6-dimethoxy-1H-
indene-1,3-dicarbonitrile (2o). 2o was purified by silica gel
chromatography (EA/PE = 25/85): yield 0.061 g, 71%, yellow green
1
solid, mp 204−206 °C; H NMR (400 MHz, CDCl3) δ 7.57 (s, 1H),
7.09 (s, 1H), 7.03 (d, J = 8.0 Hz, 1H), 6.91−6.72 (m, 3H), 6.64 (s,
1H), 6.47 (s, 1H), 3.98 (s, 3H), 3.85 (s, 3H), 3.84 (s, 3H) 3.78 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 151.1, 150.5, 149.7, 149.7,
146.5, 145.4, 144.5, 136.2, 130.7, 126.4, 118.4, 117.8, 114.5, 114.4,
112.7, 111.7, 108.5, 107.7, 107.1, 103.8, 56.4, 56.1, 55.9, 55.4 (one
OMe carbon peak was missing because of overlapping); HRMS (ESI)
+
overlapping); HRMS (ESI) m/z calcd for C33H26N3O2 [M + NH4]+
496.2020, found 496.2018.
ASSOCIATED CONTENT
+
m/z calcd for C25H21N2O5 [M + NH4]+ 429.1445, found 429.1448.
■
S
(E)-1-(3,4-Dimethoxyphenyl)-5,6-dimethoxy-2-styryl-1H-in-
dene-1,3-dicarbonitrile (2p). 2p was purified by silica gel
chromatography (EA/PE = 15/75): yield 0.060 g, 65%, yellow green
solid, mp 230−232 °C; 1H NMR (400 MHz, CDCl3) δ 7.44 (d, J = 7.0
Hz, 2H), 7.40−7.30 (m, 3H), 7.21 (d, J = 16.0 Hz, 1H), 7.14−7.05
(m, 2H), 7.00 (d, J = 16.0 Hz, 1H), 6.90 (d, J = 8.0 Hz, 1H), 6.82 (s,
1H), 6.64 (s, 1H), 4.00 (s, 3H), 3.90 (s, 3H), 3.87 (s, 3H), 3.83 (s,
3H); 13C NMR (100 MHz, CDCl3) δ 155.4, 151.5, 151.3, 150.5,
150.2, 138.3, 137.9, 135.9, 130.8, 130.2, 129.4, 128.0, 127.2, 118.8,
118.6, 1178.0, 114.4, 113.9, 112.4, 108.8, 107.5, 104.2, 56.9, 56.7, 56.4,
55.4 (one OMe carbon peak was missing because of overlapping);
* Supporting Information
Spectral data for all new compounds and X-ray structural data
of 2a (CIF). This material is available free of charge via the
Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*E-mail: duyunfeier@tju.edu.cn; jhuang@tju.edu.cn.
Notes
+
HRMS (ESI) m/z calcd for C29H28N3O4 [M + NH4]+ 482.2074,
The authors declare no competing financial interest.
found 482.2071.
ACKNOWLEDGMENTS
1-(3,4-Dimethoxyphenyl)-5,6-dimethoxy-2-methyl-1H-in-
dene-1,3-dicarbonitrile (2q). 2q was purified by silica gel
chromatography (EA/PE = 10/90): yield 0.051 g, 68%, white solid,
mp 175−177 °C; 1H NMR (400 MHz, CDCl3) δ 7.02 (s, 1H), 6.88−
6.78 (m, 3H), 6.50 (s, 1H), 3.98 (s, 3H), 3.88 (s, 3H), 3.84 (s, 3H),
3.79 (s, 3H), 2.17 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.9,
150.8, 150.0, 149.8, 135.6, 131.0, 125.0, 118.8, 117.3, 114.1, 113.5,
111.7, 108.6, 107.5, 103.5, 58.0, 56.4, 56.3, 56.1, 56.0, 13.4 (one OMe
carbon peak was missing because of overlapping); HRMS (ESI) m/z
■
Y. Du acknowledges the National Natural Science Foundation
of China (#20802048, 21072148) and Cultivation Foundation
(B) for New Faculty of Tianjin University (TJU-YFF-08B68)
for financial support.
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calcd for C22H24N3O4 [M + NH4]+ 394.1761, found 394.1760.
1-(3,4-Dimethoxyphenyl)-5,6-dimethoxy-2-propyl-1H-in-
dene-1,3-dicarbonitrile (2r). 2r was purified by silica gel
chromatography (EA/PE = 10/90): yield 0.063 g, 78%, yellow solid,
mp 131−133 °C; 1H NMR (400 MHz, CDCl3) δ 7.02 (s, 1H), 6.95−
6.76 (m, 3H), 6.48 (s, 1H), 3.98 (s, 3H), 3.89 (s, 3H), 3.83 (s, 3H),
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+
6-Methoxy-1-(4-methoxyphenyl)-2-phenyl-1H-indene-1,3-
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8.5, 2.0 Hz, 1H), 6.85 (m, 3H), 3.80 (s, 3H), 3.77 (s, 3H); 13C NMR
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