FeCl3-promoted tandem 1,4-conjugate addition/6-endo-dig cyclization/oxidation of propargylamines and benzoylacetonitriles/malononitriles: Direct access to functionalized 2-aryl-4 H -chromenes

Article abstract of DOI:10.1039/c8ob01927d

An efficient and concise procedure has been developed for the synthesis of functionalized 2-aryl-4H-chromenes based on a tandem reaction of propargylamines and benzoylacetonitriles/malononitriles in the presence of FeCl₃ as an environmentally friendly promoter. This reaction involves a highly efficient tandem sequence consisting of 1,4-conjugate addition, 6-endo-dig cyclization, and oxidation. This protocol tolerates a variety of functional groups, thereby providing a practical and efficient method for the fabrication of 2-aryl-4H-chromene skeletons.

Full text of DOI:10.1039/c8ob01927d

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COMMUNICATION
Takeharu Haino et al.
Solvent-induced emission of organogels based on tris(phenylisoxazolyl)
benzene
rsc.li/obc

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FeCl3-promoted Tandem 1,4-Conjugate Addition/6-endo-dig
Cyclyzation/Oxidation
Benzoylacetonitriles/Malononitrile:
of
Propargylamines
Direct Access
and
to
Received 00th January 20xx,
Accepted 00th January 20xx
Functionalized 2-Aryl-4H-chromenes
DOI: 10.1039/x0xx00000x
Xinwei He,* Hui Wang, Xiaoting Cai, Qianqian Li, Jiajia Tao, and Yongjia Shang*
www.rsc.org/
An efficient and concise procedure has been developed for the synthesis of functionalized 2-aryl-4H-chromenes based on
tandem reaction of propargylamines and benzoylacetonitriles/malononitrile in the presence of FeCl3 as an
a
environmentally friendly promoter. This reaction involves a highly efficient tandem sequence consisting of the 1,4-
conjugate addition, 6-endo-dig cyclyzation, and oxidation. This protocol tolerates a variety of functional groups, thereby
providing a practical and efficient method for the fabrication of 2-aryl-4H-chromene skeletons.
compounds from propargylamines and are generally catalyzed
by transition metal catalysts,7 such as Au, Cu, and Pd. In
addition, metal-free methods to synthesize heterocycles from
Introduction
Chromene is one of the privileged pharmacophores1 in
medicinal chemistry, which is capable of interacting with a
variety of cellular targets and thus possessing a wide range of
biological activities2 such as antitumor, antivascular,
antimicrobial, antioxidant, antifungal, antiviral, anticancer,
anti-HIV, antitubercular and anti-inflammatory activity.
Especially, 4H-chromene core skeletons as the derivatives of
chromenes have a broad spectrum of biological properties3
such as antimicrobial, antineoplastic, antiviral, anti-
inflammtory, etc. Accordingly, the efficient construction of the
4H-chromene structures has proven to be an inspiring
endeavor for drug discovery. Various approaches for the
preparation of 4H-chromenes have been well established.4
Due to their vital biological and pharmacological activities, it is
particularly attractive to develop a method that uses cheap
catalysts under mild reaction conditions to access 4H-
chromenes.
propargylamines have been also described.8 Iron catalyst, as
an Earth-abundant, low toxic and environmentally benign
transition metal, is attractive in organic synthesis and
tremendous development in this field has been achieved.9 Our
previous synthesis of β-alkynyl ketones and 9-arylethynyl-
2,3,4,9-tetrahydro-1H-xanthen-1-ones, which was a FeCl3-
promoted domino reactions of propargylamines and 1,3-
diketones, has been proposed to involve nucleophilic
substitution/intramolecular cyclization and subsequent
process to desired products (Scheme 1a).10 By exploring this
strategy, we presumed that the use of benzoylacetonitriles
might react with propargylamines to form a 2-aryl-4-
(arylethynyl)-4H-chromene-3-carbonitrile. Surprisingly, instead
of obtaining the expected products, we have obtained a novel
highly functionalized 2-aryl-4H-chromenes (Scheme 1b).
Herien, we report an efficient and simple strategy to prepare
2-aryl-4H-chromene derivatives from readily available
materials.
Propargylamines and their derivatives are of significance
organic compounds, easily accessed from aldehydes, terminal
alkynes, and amines.5 They have been widely utilized as key
synthetic intermediates to participate in many sorts of organic
transformations, such as in the manufacturing of different
organic substrates, natural products, and drugs.6 There are
various approaches to synthesize heterocyclic organic
a.Key Laboratory of Functional Molecular Solids, Ministry of Education, Anhui
Laboratory of Molecule-Based Materials (State Key Laboratory Cultivation Base),
College of Chemistry and Materials Science, Anhui Normal University, Wuhu
241000, P.R. China. E-mail: shyj@mail.ahnu.edu.cn, xinweihe@mail.ahnu.edu.cn
† Electronic Supplementary Information (ESI) available. Optimization of reaction
conditions and NMR spectra of the target compounds. CCDC 1841800, 1841801.
For ESI and crastallographic data in CIF or other electronic format see
DOI: 10.1039/x0xx00000x
Scheme
1 FeCl3-promoted domino Reactions of propargylamines with 1,3-
diketones or benzoylacetonitriles.
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Organic & Biomolecular Chemistry
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
FeCl3
dioxane
DCE
80
80
80
80
r.t.
60
100
80
trace
22
12
13
14
15
16
17
18
19e
Results and discussion
As a continuation of our efforts to construct novel molecular
toluene
EtOH
53
frameworks, we aimed to develop
a
practical and
trace
trace
38
regioselective synthetic route to 2-aryl-4H-chromenes. Firstly,
we focused on developing a general and efficient system to
achieve the envisioned one-pot tandem sequence and to build
the 2-aryl-4H-chromenes. We started our investigation with 2-
MeCN
MeCN
MeCN
MeCN
78
57
(3-phenyl-1-(piperidin-1-yl)prop-2-yn-1-yl)phenol
(
1a)
and
a
Reaction conditions: 2-(3-phenyl-1-(piperidin-1-yl)prop-2-yn-1-yl)-
benzoylacetonitrile (2a) as model substrates. Several reaction
parameters (promoter, solvent, and temperature) were
screened (Table 1).
phenol 1a (0.50 mmol), benzoylacetonitrile 2a (0.50 mmol), catalyst
b
(0.25 mmol), solvent (5 mL), in open air for 24 h. Isolated yields. 0.2
c
d
e
equiv of catalyst was used. 0.8 equiv of catalyst was used. Reaction
In the first assay, only trace product was detected in the
absence of promoter or in the presence of Brønsted acid (HCl)
as promoter (Table 1, entries 1, 2). Lewis acids such as AlCl3,
Sc(OTf)3, BF3·Et2O, and FeCl3 were subsequently used to allow
the formation of 2-aryl-4H-chromenes skeleton from
propargylamines, among which FeCl3 gave the best result
(Table 1, entries 3-6). Subsequently, increasing the amount of
FeCl3 from 0.5 equiv. to 0.8 equiv. gave the expected products
in 78% yield (Table 1, entry 8); further decreasing the loading
amount of FeCl3 led to an inferior result (Table 1, entry 7).
Various solvents, such as dimethylsulfoxide (DMSO),
tetrahydrofuran (THF), N,N-dimethylformamide (DMF), 1,4-
dioxane, 1,2-dichloroethane (DCE), toluene, and EtOH, were
investigated in the presence of 0.5 equiv. of FeCl3 as the Lewis
acid (Table 1, entries 9-15). No better result was obtained than
that of CH3CN, and 76% isolated yield was obtained (Table 1,
entry 6). A range of temperatures were screened to improve
the yield (Table 1, entries 16-18), and 80 °C was identified as
the optimal temperature for this domino reaction. Finally, the
yield of 4a was remarkably decreased to 57% when the
reaction time was decreased from 24 h to 12 h (Table 1, entry
19). The optimal reaction conditions thus far being developed
employing 0.5 equiv. of FeCl3 in CH3CN at 80 °C for 24 h. This
time for 12 h.
With the optimal reaction conditions in hand, various
aromatic propargylamines
1 and benzoylacetonitriles 2 were
examined to test the scope and limitation of this tandem
reaction. As shown in Table 2, this protocol was amenable to a
wide rang of propargylamines
1, and the reactions all
proceeded smoothly to yield the corresponding (Z)-3-oxo-3-
phenyl-2-(2-phenyl-4H-chromen-4-ylidene)propanenitriles in
good yields (65%-85%). First, benzoylacetonitrile 2a and 4-
chlorobenzoylacetonitrile 2b were used as a substrate to react
with different propargylamines
broad range of propargylamines
Benzoylacetonitriles could react
1
. To our delight, a remarkably
was tolerated.
efficiently with
propargylamines bearing either electron-donating or electron-
withdrawing groups on the benzene ring or Ar1 rings, and gave
the desired products in good yields (4aa-4ea). Halogens,
including F, Cl and Br, were well-tolerated, which makes this
transformation particularly attractive for increasing the
molecular complexity by transition-metal-catalyzed coupling
reactions. Compared to the yield of 4qb with the yield of 4rb
(74% vs. 67%), we found that the steric hindrance did not
influence this reaction obviously. When other propargylamines
with hetero-aromatic and alkyl group, such as 2-(1-(piperidin-
1-yl)-3-(pyridin-4-yl)prop-2-yn-1-yl)phenol and 2-(1-(piperidin-
1-yl)non-2-yn-1-yl)phenol, were used for this reaction, no
procedure
provided
(Z)-3-oxo-3-phenyl-2-(2-phenyl-4H-
chromen-4-ylidene) propanenitrile (4a) in 76% of isolated
yield.
desired product was obtained (4va
with substituents F, Me, and Cl at the para- or meta-position
of the phenyl ring of benzoylacetonitriles extensively
, 4wa). Next, substrates
Table 1 Optimization of the reaction conditions. a
2
investigated, and the results indicated that both electron-
withdrawing (F, Cl) and electrion-donating (CH3) groups were
well tolerated; the corresponding products (Table 2, 4ac, 4ad,
4ae) were obtained in 65%, 69%, 71% yields, respectively. In
contrast, switching Ar group to OAr group of
Entry
1
Catalyst
—
Solvent
MeCN
MeCN
MeCN
Temp. (°C)
Yield (%)b
trace
benzoylacetonitriles
2 and OH group to NH2 group of
80
80
80
80
80
80
80
80
80
80
80
propargylamines 1, such as phenyl 2-cyanoacetate and 2-(3-
HCl
trace
2
phenyl-1-(piperidin-1-yl)prop-2-yn-1-yl)aniline, this tandem
reaction hardly took place, and no desired product was
AlCl3
12
3
Sc(OTf)3
BF3·Et2O
FeCl3
MeCN
MeCN
MeCN
MeCN
MeCN
DMSO
THF
43
28
76
63
78
19
28
59
4
obtained (4af, 4ua).
5
6
7c
8d
9
FeCl3
FeCl3
FeCl3
FeCl3
10
11
FeCl3
DMF
2 | Org. Biomol. Chem., 2018, 00, 1-3
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cyanoacetate (3b) as the starting materials. When we tried to
do the reaction of 1a with 3a using the similar procedure used
in Table 2, we obtained only 55% yield of corresponding
product 5a, as shown in Table S1 in the electronic supporting
information (ESI) (Table S1, entry 11). Then we tried to
optimize the reaction conditions for this method by changing
reaction conditions from CH3CN to DMF at 90 °C, the
corresponding desired product 5a was obtained in 70% yield
(see ESI, Table S1, entry 6). Next, using these optimized
reaction conditions and by varying propargylamine derivatives,
we have prepared some 2-(2-aryl-4H-1-benzopyran-4-
Table 2 FeCl3-mediated tandem reactions of propargylamines and benzoylacetonitriles.
a,b
O
CN
O
Ar2
N
FeCl3 (0.5 equiv.)
MeCN, 80 oC, 24 h
CN
Ar2
+
2
R
R
Ar1
OH
1
O
4
Ar1
ylidene)propanedinitrides
(5a-5v), and the results are
summarized in Table 3. It is worth mentioning that substrate
with a bulk tert-butyl group at the ortho- and para- position of
the hydroxyl of propargylamine was also tolerated in the
reaction to give the corresponding product 5v in 78% yield.
Likewise, ethyl 2-cyanoacetate (3b) was reacted with different
propargylamines, and the corresponding (Z)-ethyl 2-cyano-2-
(2-aryl-4H-chromen-4-ylidene)acetates (Table 3, 5w−5z) were
obtained in 58%, 56%, 50%, 60% yields, respectively.
Table
3 FeCl3-catalyzed tandem reaction for the formation of 2-(2-aryl-4H-1-
benzopyran-4-ylidene)propanedinitrides. a,b
O
O
O
CN
CN
CN
Ph
Ph
Ph
N
O
O
n-C6H13
H
N
4wa, 0%
4ua, 0%
4va, 0%
a Reaction conditions: propargylamines 1 (0.5 mmol), benzoylacetonitriles 2 (0.5 mmol),
FeCl3 (0.25 mmol), CH3CN (5 mL), 80 °C, 24 h. b Isolated yields.
After having these encouraging results for the synthesis of
(Z)-3-oxo-3-phenyl-2-(2-phenyl-4H-chromen-4-
a
Reaction conditions: propargylamines 1 (0.5 mmol), malononitrile (3a) or ethyl
b
2-cyanoacetate (3b) (0.5 mmol), FeCl3 (0.25 mmol), DMF (5 mL), 90 °C, 24 h.
Isolated yields.
ylidene)propanenitriles using benzoylacetonitriles, next we
wanted to develop an alternative method where we can
access the similar products using malononitrile (3a) or ethyl 2-
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In addition, all the products were fully characterized by IR, In conclusion, a concise and efficient protocol for the synthesis
1H and 13C NMR as well as by HRMS. The structure of the of a variety of functionalized 2-aryl-4H-chromene derivatives
products has also been confirmed by X-ray crystallographic has been developed. The reaction is carried out with easily
analysis of compounds 4f and 5a (see ESI).
accessible for substituted propargylamines bearing electron-
To gain insight into the possible mechanism of this reaction, rich and electron-poor groups, and FeCl3 as a non-expensive
a few control experiments were carried out (Scheme 2). When and eco-friendly promoter. Due to the described usefulness of
2-(3-phenyl-1-(piperidin-1-yl)prop-2-yn-1-yl)-phenol
1a 4H-chromene derivatives, such simple reaction conditions and
reacted with benzoylacetonitrile 2a under the nitrogen functional group tolerance are offering a new attractive
atmosphere with the standard reaction conditions, the method for access to such structures. Therefore, from these
corresponding product 4aa was obtained only in 20% yield and results, it can be envisioned that this procedure will find many
51% of substrate 1a was recycled. We next treated this applications in the synthesis of pharmacological compounds.
reaction with an oxygen balloon as the oxidant, the desired
product 4aa was obtained in 81% yield. These results indicated
Experimental
that the oxidation process possibly proceeded with oxygen in
air as oxidant.
General experimental method
Unless otherwise specified, all reagents and starting materials
were purchased from commercial sources and used as
received, and the solvents were purified and dried using
standard procedures. The chromatography solvents were
technical grade and distilled prior to use. Flash
chromatography was performed using 200-300 mesh silica gel
with the indicated solvent system according to standard
Scheme 2 Control experiments.
techniques. The NMR spectra were recorded with a Bruker
1
Avance 300 spectrometer (300 MHz for H) and Avance 500
spectrometer (125 MHz for 13C) with CDCl3 as solvent. NMR
On the basis of the experimental results obtained above and
those described in previous reports,11 a plausible mechanism
multiplicities are abbreviated as follows: s = singlet, d =
was proposed (Scheme 3). The propargylamines 1a first
doublet, t = triplet, q = quartet. All new products were further
resulted in the generation of an alkynyl ortho-quinone methide
characterized by HRMS (high resolution mass spectrometry);
(o-AQM) intermediate with releasing piperidine in the
presence of Lewis acid as reported lituratures.12 Then, an
HRMS spectra were obtained with an Agilent 6200 using a
quadrupole time-of-flight mass spectrometer equipped with
intermolecular 1,4-conjugate addition of intermediate
tautomerized from benzoylacetonitriles produced
intermediate , which would further undergo 6-endo-dig
cyclyzation to give the intermediate , an iron complex with
the coordination of C≡N bond to iron atom. Following the
oxidation of intermediate , in situ quickly formed (Z)-isomer
intermediate with an exocyclic double bond to promote the
degree of conjugation in the presence of air as oxidant. Finally,
intermediate underwent protodeauration to afford the final
(Z)-isomers product
A
an APCI source. The IR spectra were measured with an
IRPrestige-21 spectrometer as dry pellets (KBr), and the peaks
are reported in terms of the wavenumber (cm-1). The melting
points were measured using SGWX-4 melting point apparatus.
General procedure for the synthesis of (Z)-3-oxo-3-aryl-2-
2
B
C
C
(2-aryl-4H-chromen-4-ylidene)propanenitriles
FeCl3 (0.25 mmol) was added to a stirred solution of
propargylamines (0.5 mmol), and benzoylacetonitriles (0.5
4. Anhydrous
D
1
2
D
mmol) in acetonitrile (5 mL). The mixture was heated at 80 °C
for 24 h in an oil bath. Upon completion of the reaction, the
mixture was cooled to room temperature, diluted with CH2Cl2
(3 × 20 mL), and washed with water. The organic layers were
combined, dried over Na2SO4, filtered, and then evaporated in
vacuum. The residue was purified by flash column
chromatography on silica gel with ethyl acetate and petroleum
4.
O
OH
Lewis acid
CN
CN
O
Ar
Ar
N
A
2
Ar
FeCl3
1,4-conjugate
addition
N
OH
B
FeCl3
O
OH
6-endo-dig
cyclyzation
piperidine
(o-AQM)
ether as the eluting solvent to produce the product 4.
1a
HCl
General procedure for the synthesis of 2-(2-aryl-4H-
chromen-4-ylidene)malononitriles 5. Anhydrous FeCl3 (0.25
O
O
O
N
N
CN
Ar
Ar
Ar
Cl
Cl
HCl
Fe
Ph
Fe
Ph
mmol) was added to a stirred solution of propargylamines
1
Cl
Cl
air
oxidation
FeCl3
Ph
O
C
(0.5 mmol), and malononitrile 3a (0.5 mmol) in DMF (5 mL).
The mixture was heated at 90 °C for 24 h in an oil bath. Upon
completion of the reaction, the mixture was cooled to room
temperature, diluted with CH2Cl2 (3 × 20 mL), and washed with
water. The organic layers were combined, dried over Na2SO4,
filtered, and then evaporated in vacuum. The residue was
purified by flash column chromatography on silica gel with
O
D
O
4
Scheme 3 Proposed mechanism for the FeCl3-mediated tandem reactions of
propargylamines and benzoylacetonitriles.
Conclusions
4 | Org. Biomol. Chem., 2018, 00, 1-3
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ethyl acetate and petroleum ether as the eluting solvent to 1653, 1319, 1301, 1244, 765, 744, 717, 694, 669 cm-1; HRMS
produce the product
5.
(APCI) calcd for [C24H14NO2F+H]+ 368.1081, found 368.1078.
(Z)-3-Oxo-3-phenyl-2-(2-phenyl-4H-chromen-4-
(Z)-2-(6-Methyl-2-phenyl-4H-chromen-4-ylidene)-3-oxo-3-
ylidene)propanenitrile (4aa). Petroleum ether/ethyl acetate phenylpropanenitrile (4fa). Petroleum ether/ethyl acetate 8:1;
8:1; yellow solid; yield 78% (126 mg, 0.39 mmol); mp 174-176 yellow solid; yield 83% (152 mg, 0.42 mmol); mp 187-189 °C;
°C; 1H NMR (300 MHz, CDCl3) δ 9.23 (d, J = 6.3 Hz, 1H), 8.26 (s, 1H NMR (300 MHz, CDCl3) δ 9.03 (s, 1H), 8.27 (s, 1H), 7.96 (d, J
1H), 7.93-7.98 (m, 4H), 7.71 (d, J = 6.0 Hz, 1H), 7.51-7.60 (m, = 7.8 Hz, 2H), 7.91 (d, J = 7.8 Hz, 2H), 7.48-7.61 (m, 7H), 7.37 (s,
7H), 7.29 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 192.1, 157.4, 1H), 2.52 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 192.3, 157.3,
153.7, 150.6, 138.4, 133.7, 132.9, 131.6, 131.3, 129.2, 129.1, 151.9, 150.7, 138.6, 135.5, 135.0, 132.8, 131.5, 129.2, 129.0,
128.4, 126.5, 126.4, 125.5, 122.2, 119.1, 118.6, 103.5, 92.1; IR 128.4, 126.4, 126.0, 122.4, 118.8, 118.4, 103.4, 91.5, 21.4; IR
(KBr) ν 3057, 2183, 1639, 1278, 1247, 765, 744, 713, 682 cm-1; (KBr) ν 3055, 3037, 2189, 1622, 1311, 1246, 821, 765, 725, 686
HRMS (APCI) calcd for [C24H15NO2+H]+ 350.1176, found cm-1; HRMS (APCI) calcd for [C25H17NO2+H]+ 364.1332, found
350.1177.
(Z)-2-(2-(4-Ethylphenyl)-4H-chromen-4-ylidene)-3-oxo-3-
364.1335.
(Z)-2-(2-(4-Fluorophenyl)-6-methyl-4H-chromen-4-ylidene)-
phenylpropanenitrile (4ba). Petroleum ether/ethyl acetate 3-oxo-3-phenylpropanenitrile (4ga). Petroleum ether/ethyl
8:1; yellow solid; yield 81% (154 mg, 0.41 mmol); mp 136-138 acetate 8:1; yellow solid; yield 69% (133 mg, 0.35 mmol); mp
1
°C; 1H NMR (300 MHz, CDCl3) δ 9.22 (d, J = 7.5 Hz, 1H), 8.28 (s, 137-139 °C; H NMR (300 MHz, CDCl3) δ 9.03 (s, 1H), 8.22 (s,
1H), 7.96 (d, J = 6.6 Hz, 2H), 7.84 (d, J = 7.5 Hz, 2H), 7.70 (d, J = 1H), 7.85-8.05 (m, 4H), 7.58 (d, J = 7.2 Hz, 1H), 7.51 (d, J = 7.2
6.3 Hz, 1H), 7.55 - 7.63 (m, 2H), 7.50 (t, J = 7.5 Hz, 3H), 7.33 (s, Hz, 2H), 7.47 (s, 2H), 7.18 (t, J = 8.1 Hz, 2H), 2.51 (s, 3H); 13C
1H), 7.30 (s, 1H), 2.72 (q, J = 7.5 Hz, 2H), 1.27 (t, J = 7.5 Hz, 3H); NMR (125 MHz, CDCl3) δ 192.6, 165.1 (d, J = 253.5 Hz), 156.7,
13C NMR (125 MHz, CDCl3) δ 192.3, 157.8, 153.7, 151.0, 148.7, 152.2, 150.8, 138.9, 136.0, 135.4, 133.2, 129.6, 129.1, 129.0 (d,
138.6, 133.6, 132.8, 129.2, 128.6, 128.4, 126.5, 125.5, 122.5, J = 8.9 Hz), 128.8, 128.1 (d, J = 3.0 Hz), 126.4, 122.6, 119.1,
119.2, 118.6, 103.1, 91.5, 28.9, 15.3; IR (KBr) ν 3070, 2185, 118.7, 116.7 (d, J = 22.0 Hz), 103.5, 92.1, 21.8; IR (KBr) ν 3053,
1637, 1311, 1296, 1242, 831, 771, 744, 721, 665cm-1; HRMS 3034, 2189, 1647, 1280, 1247, 835, 800, 748, 707, 686 cm-1;
(APCI) calcd for [C26H19NO2+H]+ 378.1489, found 378.1482.
(Z)-2-(2-(4-Chlorophenyl)-4H-chromen-4-ylidene)-3-oxo-3-
phenylpropanenitrile (4ca). Petroleum ether/ethyl acetate
HRMS (APCI) calcd for [C25H16NO2F+H]+ 382.1238, found
382.1242.
(Z)-2-(2-(4-Bromophenyl)-6-methoxy-4H-chromen-4-
8:1; saffron yellow solid; yield 71% (138 mg, 0.36 mmol); mp ylidene)-3-oxo-3-phenylpropanenitrile
(4ha)
.
Petroleum
1
182-184 °C; H NMR (300 MHz, CDCl3) δ 9.20 (s, 2H), 8.19 (s, ether/ethyl acetate 8:1; yellow solid; yield 71% (164 mg, 0.36
1
2H), 7.98 (d, J = 7.2 Hz, 2H), 7.86 (d, J = 7.2 Hz, 1H), 7.69-7.74 mmol); mp 177-179 °C; H NMR (300 MHz, CDCl3) δ 9.37 (s,
(m, 1H), 7.46-7.63 (m, 5H), 7.29 (s, 1H); 13C NMR (125 MHz, 1H), 8.22 (s, 1H), 7.95 (d, J = 6.3 Hz, 2H), 7.85 (d, J = 7.8 Hz,
CDCl3) δ 192.0 156.1, 153.6, 150.1, 138.3, 137.9, 133.8, 133.0, 2H), 7.78 (d, J = 7.8 Hz, 1H), 7.58 (d, J = 6.6 Hz, 1H), 7.42-7.52
129.4, 129.2, 129.0, 128.5, 127.6, 127.4, 126.5, 125.7, 119.1, (m, 3H), 6.99 (s, 1H),6.97 (s, 1H), 3.88 (s, 3H); 13C NMR (125
118.60, 103.6, 92.7; IR (KBr) ν 2181, 1639, 1246, 831, 763, 742, MHz, CDCl3) δ 192.0, 162.7, 157.5, 152.5, 148.9, 138.4, 136.4,
719, 707 cm-1; HRMS (APCI) calcd for [C24H14NO2Cl+H]+ 132.9, 129.2, 128.9, 128.4, 128.2, 123.3, 121.8, 120.7, 120.2,
384.0786, found 384.0787.
118.3, 114.6, 102.1, 91.6, 55.6; IR (KBr) ν 3064, 2181, 1641,
1280, 1244, 866, 831, 725, 704, 686 cm-1; HRMS (APCI) calcd
(Z)-2-(2-(4-Bromophenyl)-4H-chromen-4-ylidene)-3-oxo-3-
phenylpropanenitrile (4da). Petroleum ether/ethyl acetate for [C25H16NO3Br+H]+ 458.0386, found 458.0381.
8:1; saffron yellow solid; yield 73% (157 mg, 0.37 mmol); mp
(Z)-2-(6-Chloro-2-phenyl-4H-chromen-4-ylidene)-3-oxo-3-
1
199-201 °C; H NMR (300 MHz, CDCl3) δ 9.21 (s, 1H), 8.20 (s, phenylpropanenitrile (4ia). Petroleum ether/ethyl acetate 8:1;
1H), 7.97 (d, J = 6.3 Hz, 2H), 7.77 (d, J = 6.6 Hz, 2H), 7.72 (s, yellow solid; yield 70% (134 mg, 0.35 mmol); mp 193-195 °C;
1H), 7.62 (d, J = 8.1 Hz, 3H), 7.58 (s, 1H), 7.47-7.54 (m, 3H); 13C 1H NMR (300 MHz, CDCl3) δ 9.22 (s, 1H), 8.16 (s, 1H), 7.97 (d, J
NMR (125 MHz, CDCl3) δ 192.1, 156.1, 153.5, 150.2, 138.2, = 6.3 Hz, 2H), 7.88 (d, J = 4.8 Hz, 2H), 7.58-7.66 (m, 2H), 7.52
133.9, 133.0, 132.3, 130.3, 129.7, 129.2, 128.5, 127.6, 126.5, (d, J = 6.9 Hz, 6H); 13C NMR (125 MHz, CDCl3) δ 191.7, 157.2,
126.3, 125.7, 119.0, 118.6, 105.1, 103.5, 92.7; IR (KBr) ν 3053, 152.1, 148.6, 138.0, 133.8, 133.2, 131.8, 131.1, 129.7, 129.3,
3034, 2181, 1647, 1323, 1303, 1246, 829, 765, 755, 719, 707 129.1, 128.9, 128.5, 126.3, 125.8, 121.4, 120.2, 120.1, 105.0,
cm-1; HRMS (APCI) calcd for [C24H14NO2Br+H]+ 428.0281, found 103.2, 92.9; IR (KBr) ν 3057, 3034, 2185, 1641, 1280, 1244,
428.0276.
(Z)-2-(2-(2-Fluorophenyl)-4H-chromen-4-ylidene)-3-oxo-3-
phenylpropanenitrile (4ea). Petroleum ether/ethyl acetate
850, 763, 744, 707, 680 cm-1; HRMS (APCI) calcd for
[C24H14NO2Cl+H]+ 384.0786, found 384.0787.
(Z)-2-(6-Chloro-2-(p-tolyl)-4H-chromen-4-ylidene)-3-oxo-3-
8:1; yellow solid; yield 75% (139 mg, 0.38 mmol); mp 148-150 phenylpropanenitrile (4ja). Petroleum ether/ethyl acetate 8:1;
°C; 1H NMR (300 MHz, CDCl3) δ 9.19 (s, 1H), 7.88-8.09 (m, 4H), yellow solid; yield 73% (147 mg, 0.37 mmol); mp 156-158 °C;
7.70 (s, 1H), 7.58 (s, 1H), 7.50 (s, 5H), 7.29 (s, 1H), 7.19 (s, 1H); 1H NMR (300 MHz, CDCl3) δ 9.22 (s, 1H), 8.18 (s, 1H), 7.97 (d, J
13C NMR (125 MHz, CDCl3) δ 191.6, 160.5 (d, J = 255.7 Hz), = 7.8 Hz, 2H), 7.79 (d, J = 7.8 Hz, 2H), 7.28-7.68 (m, 5H), 7.29
153.6, 152.6, 149.6, 138.0, 133.7, 133.1, 132.8 (d, J = 9.0 Hz), (d, J = 8.1 Hz, 1H), 7.23 (s, 1H), 2.43 (s, 3H); 13C NMR (125 MHz,
129.4, 129.0, 128.5, 126.4, 125.6, 124.6 (d, J = 3.3 Hz), 118.9, CDCl3) δ 191.8, 157.6, 152.1, 148.8, 142.7, 138.2, 133.7, 133.1,
118.6, 117.0 (d, J = 22.5 Hz), 107.8, 107.7, 93.2; IR (KBr) ν 2185, 131.0, 129.9, 129.3, 128.5, 128.2, 126.3, 125.8, 120.3, 120.0,
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102.7, 21.6; IR (KBr) ν 3061, 3034, 2181, 1641, 1321, 1301, 1325, 1305, 1244, 842, 817, 767, 754, 740 cm-1; HRMS (APCI)
1244, 856, 815,769, 709, 682 cm-1; HRMS (APCI) calcd for calcd for [C24H13NO2Cl2+H]+ 418.0396, found 418.0398.
[C25H16NO2Cl+H]+ 398.0942, found 398.0941.
(Z)-2-(2-(4-Bromophenyl)-4H-chromen-4-ylidene)-3-(4-
chlorophenyl)-3-oxopropanenitrile (4db) Petroleum
(Z)-2-(6-Bromo-2-phenyl-4H-chromen-4-ylidene)-3-oxo-3-
.
phenylpropanenitrile (4ka). Petroleum ether/ethyl acetate ether/ethyl acetate 8:1; yellow solid; yield 71% (166 mg, 0.36
8:1; yellow solid; yield 71% (153 mg, 0.36 mmol); mp 204-206 mmol); mp 191-193 °C; 1H NMR (300 MHz, CDCl3) δ 9.20 (d, J =
1
°C; H NMR (300 MHz, CDCl3) δ 9.36 (s, 1H), 8.14 (s, 1H), 7.98 8.1 Hz, 1H), 8.32 (s, 1H), 7.90 (d, J = 8.4 Hz, 2H), 7.80 (d, J = 8.4
(d, J = 6.6 Hz, 2H), 7.89 (s, 2H), 7.79 (s, 1H), 7.60 (d, J = 6.7 Hz, Hz, 2H), 7.73 (d, J = 7.5 Hz, 1H), 7.61 (dd, J = 17.0, 8.4 Hz, 3H),
1H), 7.43 - 7.51 (m, 5H), 7.43 (s, 1H); 13C NMR (125 MHz, 7.49 (s, 2H), 7.46 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 190.8,
CDCl3) δ 191.7, 157.1, 152.5, 148.3, 138.0, 136.6, 133.2, 131.8, 156.6, 153.6, 150.9, 139.3, 136.7, 134.0, 132.4, 131.0, 130.6,
131.0, 129.3, 129.1, 128.8, 128.5, 126.3, 121.4, 120.6, 120.3, 130.2, 128.8, 127.8 126.6, 126.5, 125.8, 122.1, 119.0, 118.7,
118.5, 103.3, 93.0; IR (KBr) ν 3057, 3034, 2181, 1641, 1280, 103.6, 91.9; IR (KBr) ν 3034,3016, 2185, 1653, 1330, 1315,
1244, 858, 767, 742, 709, 682 cm-1; HRMS (APCI) calcd for 1249, 833, 813, 785, 767, 669 cm-1; HRMS (APCI) calcd for
[C24H14NO2Br+H]+ 428.0281, found 428.0276.
[C24H13NO2ClBr+H]+ 461.9891, found 461.9894.
(Z)-2-(6-Bromo-2-(p-tolyl)-4H-chromen-4-ylidene)-3-oxo-3-
(Z)-3-(4-Chlorophenyl)-2-(2-(2-fluorophenyl)-4H-chromen-
phenylpropanenitrile (4la). Petroleum ether/ethyl acetate 8:1; 4-ylidene)-3-oxopropanenitrile (4eb). Petroleum ether/ethyl
yellow solid; yield 75% (167 mg, 0.38 mmol); mp 165-167 °C; acetate 8:1; yellow solid; yield 78% (156 mg, 0.39 mmol); mp
1H NMR (300 MHz, CDCl3) δ 9.36 (s, 1H), 8.19 (s, 1H), 7.96 (d, J 167-169 °C; 1H NMR (300 MHz, CDCl3) δ 9.19 (d, J = 8.1 Hz, 1H),
= 6.6 Hz, 2H), 7.78 (s, 3H), 7.59 (d, J = 6.0 Hz, 1H), 7.38-7.56 (m, 8.20 (s, 1H), 7.90 (t, J = 7.5 Hz, 3H), 7.71 (d, J = 7.5 Hz, 1H),
3H), 7.29 (s, 2H), 2.42 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 7.43-7.57 (m, 4H), 7.27-7.36 (m, 1H), 7.17-7.24 (m, 1H); 13C
191.8, 157.5, 152.5, 148.7, 142.7, 138.2, 136.5, 136.2, 133.1, NMR (125 MHz, CDCl3) δ 190.8, 161.0 (d, J = 256.3 Hz), 154.1,
129.8, 129.3, 128.8, 128.5, 128.2, 126.3, 121.6, 120.7, 120.3, 153.5, 150.6, 139.8, 136.8, 134.3, 133.4 (d, J = 9.2 Hz), 131.5,
118.4, 104.5, 102.7, 92.3, 21.6; IR (KBr) ν 2966, 2189, 1637, 131.1, 129.6, 129.4, 129.2, 126.8, 126.1,125.1 (d, J = 3.5 Hz),
1313, 1296, 1244, 854, 800, 775, 744, 721 cm-1; HRMS (APCI) 122.2, 119.2, 119.0, 118.9, 117.4 (d, J = 22.5 Hz), 108.2, 108.1,
calcd for [C25H16NO2Br+H]+ 442.0437, found 442.0438.
92.9; IR (KBr) ν 2185, 1637, 1328, 1311, 1253, 827, 775, 758,
744, 694 cm-1; HRMS (APCI) calcd for [C24H13NO2ClF+H]+
(Z)-3-(4-Chlorophenyl)-3-oxo-2-(2-phenyl-4H-chromen-4-
ylidene)propanenitrile (4ab). Petroleum ether/ethyl acetate 402.0692, found 402.0690.
8:1; yellow solid; yield 81% (157 mg, 0.41 mmol); mp 162-164
(Z)-3-(4-Chlorophenyl)-2-(6-methyl-2-phenyl-4H-chromen-
°C; 1H NMR (300 MHz, CDCl3) δ 9.22 (d, J = 7.8 Hz, 1H), 8.37 (s, 4-ylidene)-3-oxopropanenitrile (4fb). Petroleum ether/ethyl
1H), 7.84-8.10 (m, 5H), 7.74 (t, J = 7.2 Hz, 1H), 7.48-7.63 (m, acetate 8:1; yellow solid; yield 85% (170 mg, 0.43 mmol); mp
6H), 7.46 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 190.9, 157.9, 150-152 °C; H NMR (300 MHz, CDCl3) δ 8.94 (s, 1H), 8.31 (s,
1
153.8, 151.2, 139.1, 136.9, 133.9, 131.8, 131.3, 130.6, 129.1, 1H), 7.91 (s, 4H), 7.49 (s, 6H), 7.47 (s, 1H), 2.46 (s, 3H); 13C
128.7, 126.5, 125.7, 122.3, 119.1, 118.7, 103.6, 91.4; IR (KBr) ν NMR (125 MHz, CDCl3) δ 190.8, 157.8, 151.9, 151.3, 139.0,
2181, 1639, 1323, 1246, 831, 763,742,707,682 cm-1; HRMS 137.0, 135.6, 135.2, 131.7, 131.2, 130.6, 129.1, 128.7, 126.4,
(APCI) calcd for [C24H14NO2Cl+H]+ 384.0786, found 384.0785.
118.6, 118.4, 103.6, 21.4; IR (KBr) ν 3057, 3037, 2185, 1637,
(Z)-3-(4-Chlorophenyl)-2-(2-(4-ethylphenyl)-4H-chromen-4- 1332, 1311, 1249, 823, 792, 773, 761, 682 cm-1; HRMS (APCI)
ylidene)-3-oxopropanenitrile (4bb). Petroleum ether/ethyl calcd for [C25H16NO2Cl+H]+ 398.0942, found 398.0944.
acetate 8:1; saffron yellow solid; yield 78% (160 mg, 0.39
(Z)-3-(4-Chlorophenyl)-2-(2-(4-fluorophenyl)-6-methyl-4H-
1
mmol); mp 146-148 °C; H NMR (300 MHz, CDCl3) δ 9.03 (s, chromen-4-ylidene)-3-oxopropanenitrile (4gb) Petroleum
.
1H), 9.30 (s, 1H), 7.89 (dd, J = 7.7 Hz, 4H), 7.71 (q, J = 6.9 Hz, ether/ethyl acetate 8:1; saffron yellow solid; yield 66% (137
1
1H), 7.58 (d, J = 8.1 Hz, 1H), 7.47 (d, J = 6.9 Hz, 3H), 7.35 (s, mg, 0.33 mmol); mp 191-193 °C; H NMR (300 MHz, CDCl3) δ
1H), 7.32 (s, 1H), 2.73 (q, J = 6.6 Hz, 2H), 1.28 (t, J = 6.6 Hz, 3H); 8.93 (s, 1H), 8.26 (s, 1H), 7.84-8.04 (m, 4H), 7.45-7.55 (m, 4H),
13C NMR (125 MHz, CDCl3) δ 191.0, 158.3, 153.8, 151.6, 148.9, 7.22 (s, 1H), 7.19 (d, J = 8.4 Hz, 1H), 2.49 (s, 3H); 13C NMR (125
138.9, 137.1, 133.8, 130.5, 128.7, 126.6, 125.6, 119.1, 118.7, MHz, CDCl3) δ 191.4, 165.2 (d, J = 254.0 Hz), 157.2, 152.3,
103.1, 90.8, 28.9, 15.2; IR (KBr) ν 3064, 3034, 2181, 1645, 151.5, 139.4, 137.4, 136.2, 135.6, 135.4 (d, J = 7.7 Hz), 131.3,
1323, 1303, 1242, 821, 802, 704, 688 cm-1; HRMS (APCI) calcd 131.0, 129.4, 129.1, 129.0, 128.0 (d, J = 2.6 Hz), 126.3, 122.7,
for [C26H18NO2Cl+H]+ 412.1099, found 412.1095.
119.1, 118.7, 116.7 (d, J = 22.1 Hz), 103.6, 91.3, 21.8; IR (KBr) ν
(Z)-3-(4-Chlorophenyl)-2-(2-(4-chlorophenyl)-4H-chromen-
3034, 3012, 2185, 1637, 1323, 1303, 1247, 844, 817, 779, 758,
4-ylidene)-3-oxopropanenitrile (4cb). Petroleum ether/ethyl 669 cm-1; HRMS (APCI) calcd for [C25H15NO2ClF+H]+ 416.0848,
acetate 8:1; yellow solid; yield 67% (141 mg, 0.34 mmol); mp found 416.0849.
1
185-187 °C; H NMR (300 MHz, CDCl3) δ 9.19 (s, 1H), 8.29 (s,
(Z)-2-(6-Chloro-2-phenyl-4H-chromen-4-ylidene)-3-(4-
(4ib) Petroleum
1H), 7.90 (t, J = 8.1 Hz, 4H), 7.73 (t, J = 8.1 Hz, 1H), 7.57 (d, J = chlorophenyl)-3-oxopropanenitrile
.
8.4 Hz, 1H), 7.48 (d, J = 8.1 Hz, 4H), 7.29 (s, 1H); 13C NMR (125 ether/ethyl acetate 8:1; yellow solid; yield 71% (150 mg, 0.36
1
MHz, CDCl3) δ 194.8, 147.7, 143.3, 137.4, 136.9, 136.6, 134.4, mmol); mp 185-187 °C; H NMR (300 MHz, CDCl3) δ 9.22 (s,
131.9, 129.5, 129.3, 129.1, 128.5, 123.6, 123.0, 121.3, 117.2, 1H), 8.27 (s, 1H), 7.91 (d, J = 6.9 Hz, 4H), 7.68 (d, J = 8.1 Hz,
94.4, 49.4, 44.4, 21.0, 20.7; IR (KBr) ν 3034, 3016, 2189, 1637, 1H), 7.49-7.59 (m, 5H), 7.47 (s, 1H); 13C NMR (125 MHz, CDCl3)
δ 190.5, 157.7, 152.2, 149.3, 139.5, 136.5, 134.0, 133.8, 132.0,
6 | Org. Biomol. Chem., 2018, 00, 1-3
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131.2, 131.0, 130.9, 130. 7, 129.2, 128.8, 126.4, 125. 8, 121.5, 154.2, 152.1, 139.2, 137.7, 134.1, 131.3, 130.8, 129.4, 129.0,
120.1, 103.3, 92.1; IR (KBr) ν 2185, 1637, 1321, 1305, 1265, 128.8, 126.9, 125.9, 123.9, 123.1, 119.5, 119.0, 115.0, 102.8,
802, 765, 744, 717, 692 cm-1; HRMS (APCI) calcd for 90.5, 56.0; IR (KBr) ν 3057, 3034, 2181, 1637, 1328, 1311,
[C24H13NO2Cl2+H]+ 418.0396, found 418.0395.
1251, 850, 827, 773, 752, 740 cm-1; HRMS (APCI) calcd for
(Z)-3-(4-Chlorophenyl)-2-(6-methyl-2-(p-tolyl)-4H-chromen- [C25H16NO3Cl+H]+ 414.0891, found 414.0889.
4-ylidene)-3-oxopropanenitrile (4jb). Petroleum ether/ethyl
(Z)-3-(4-Chlorophenyl)-2-(2-(4-fluorophenyl)-4H-chromen-
acetate 8:1; saffron yellow solid; yield 65% (142 mg, 0.33 4-ylidene)-3-oxopropanenitrile (4ob). Petroleum ether/ethyl
1
mmol); mp 194-196 °C; H NMR (300 MHz, CDCl3) δ 9.19 (s, acetate 8:1; yellow solid; yield 68% (136 mg, 0.34 mmol); mp
1H), 8.28 (s, 1H), 7.91 (d, J = 7.5 Hz, 2H), 7.80(d, J = 7.5 Hz, 3H), 168-170 °C; 1H NMR (300 MHz, CDCl3) δ 9.20 (d, J = 7.4 Hz, 1H),
7.64 (s, 1H), 7.43-7.55 (m, 3H), 7.31 (d, J = 8.1 Hz, 1H), 2.44 (s, 8.31 (s, 1H), 7.83-8.06 (m, 4H), 7.74 (s, 1H), 7.57 (d, J = 7.4 Hz,
3H); 13C NMR (125 MHz, CDCl3) δ 194.1, 158.1, 152.2, 149.6, 1H), 7.36-7.53 (m, 3H), 7.19 (s, 2H) ; 13C NMR (125 MHz, CDCl3)
142.9, 139.3, 136.7, 133.9, 131.1, 130.6, 129.9, 128.8, 128.1, δ 191.2, 165.3 (d, J = 254.2 Hz), 157.2, 154.0, 151.4, 139.6,
126.4, 125.8, 121.8, 120.1, 102.8, 91.5, 21.6; IR (KBr) ν 3037, 137.2, 134.4, 131.0, 129.1 (d, J = 8.9 Hz), 126.9, 126.1, 122.5,
3012, 2185, 1637, 1321, 1309, 1247, 842, 815, 779, 754, 694 119.4, 119.0, 116.8 (d, J = 22.1 Hz), 103.6, 92.0; IR (KBr) ν 3037,
cm-1; HRMS (APCI) calcd for [C25H15NO2Cl2+H]+ 432.0553, found 3016, 2185, 1637, 1323, 1307, 1242, 848, 835, 767, 754, 744
432.0560.
(Z)-2-(6-Bromo-2-phenyl-4H-chromen-4-ylidene)-3-(4-
chlorophenyl)-3-oxopropanenitrile (4kb) Petroleum
cm-1; HRMS (APCI) calcd for [C24H13NO2ClF+H]+ 402.0692,
found 402.0695.
.
(Z)-3-(4-Chlorophenyl)-2-(2-(4-chlorophenyl)-6-methyl-4H-
ether/ethyl acetate 8:1; yellow solid; yield 73% (170 mg, 0.37 chromen-4-ylidene)-3-oxopropanenitrile (4pb)
.
Petroleum
1
mmol); mp 196-198 °C; H NMR (300 MHz, CDCl3) δ 9.35 (s, ether/ethyl acetate 8:1; saffron yellow solid; yield 69% (150
1
1H), 8.26 (s, 1H), 7.91 (d, J = 7.2 Hz, 4H), 7.81 (d, J = 7.8 Hz, mg, 0.35 mmol); mp 207-209 °C; H NMR (300 MHz, CDCl3) δ
1H), 7.51 (d, J = 8.1 Hz, 5H), 7.47 (s, 1H); 13C NMR (125 MHz, 9.01 (s, 1H), 8.33 (s, 1H), 7.88 (t, J = 9.0 Hz, 4H), 7.47-7.57 (m,
CDCl3) δ 190.5, 157.6, 152.6, 149.0, 139.5, 136.8, 136.5, 132.0, 4H), 7.46 (s, 2H), 2.52 (s, 3H) 55 (m, 4H), 7.22 (s, 1H), 7.18 (d, J
130.9, 130.7, 129.2, 128.8, 126.4, 126.3, 121.5, 120.5, 120.3, = 8.7 Hz, 1H), 2.49 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 191.0,
118.6, 103.3, 92.2; IR (KBr) ν 3061, 3053, 2185, 1637, 1427, 156.5, 151.9, 151.0, 139.1, 138.0, 136.9, 135.8, 135.3, 130.6,
835, 800, 779, 748, 707 cm-1; HRMS (APCI) calcd for 129.4, 128.7, 127.6, 125.9, 122.3, 118.7, 118.4, 103.5, 91.3,
[C24H13NO2ClBr+H]+ 461.9891, found 461.9890.
21.4; IR (KBr) ν 3034, 3016, 2185, 1637, 1305, 1286, 1259, 831,
821, 779, 758, 671 cm-1; HRMS (APCI) calcd for
(Z)-2-(6-Bromo-2-(p-tolyl)-4H-chromen-4-ylidene)-3-(4-
chlorophenyl)-3-oxopropanenitrile
(4lb)
.
Petroleum [C25H15NO2Cl2+H]+ 432.0553, found 432.0555.
ether/ethyl acetate 8:1; yellow solid; yield 71% (171 mg, 0.36 (Z)-3-(4-Chlorophenyl)-2-(6-methoxy-2-phenyl-4H-
mmol); mp 192-194 °C; H NMR (300 MHz, CDCl3) δ 9.35 (s, chromen-4-ylidene)-3-oxopropanenitrile (4qb) Petroleum
1
.
1H), 8.30 (s, 1H), 7.90 (d, J = 7.8 Hz, 2H), 7.81 (d, J = 7.5 Hz, ether/ethyl acetate 8:1; yellow solid; yield 74% (152 mg, 0.37
1
3H), 7.49 (s, 1H), 7.46 (s, 2H), 7.30 (d, J = 7.5 Hz, 2H), 2.44 (s, mmol); mp 182-184 °C; H NMR (300 MHz, CDCl3) δ 8.56 (s,
3H); 13C NMR (125 MHz, CDCl3) δ 190.6, 158.0, 152.6, 149.3, 1H), 8.41 (s, 1H), 7.89-7.96 (m, 4H), 7.46-7.55 (m, 5H), 7.46 (s,
142.9, 139.3, 136.7, 130.6, 129.9, 128.8, 128.1, 126.4, 121.7, 1H), 7.32-7.36 (m, 1H), 3.92 (s, 3H); 13C NMR (125 MHz, CDCl3)
120.6, 120.3, 118.5, 102.8, 91.5, 21.6; IR (KBr) ν 21815, 1643, δ 191.0, 158.0, 156.8, 148.7, 138.9, 137.3, 131.7, 131.4, 130.5,
1321, 1301, 1244, 850, 819, 763, 744, 721 cm-1; HRMS (APCI) 129.1, 128.7, 126.4, 124.0, 122.9, 119.9, 106.6, 103.3, 90.2,
calcd for [C25H15NO2ClBr+H]+ 476.0047, found 476.0048.
56.2; IR (KBr) ν 3057,3034, 2181, 1647, 1323, 1303, 1246, 852,
829, 765, 740, 709 cm-1; HRMS (APCI) calcd for
(Z)-3-(4-Chlorophenyl)-3-oxo-2-(2-(p-tolyl)-4H-chromen-4-
ylidene)propanenitrile (4mb). Petroleum ether/ethyl acetate [C25H16NO3Cl+H]+ 414.0891, found 414.0883.
8:1; saffron yellow solid; yield 83% (167 mg, 0.42 mmol); mp
(Z)-3-(4-Chlorophenyl)-2-(8-methoxy-2-phenyl-4H-
1
163-165 °C; H NMR (300 MHz, CDCl3) δ 9.04 (s, 1H), 8.30 (s, chromen-4-ylidene)-3-oxopropanenitrile (4rb) Petroleum
.
1H), 7.87 (q, J = 8.1 Hz, 4H), 7.71 (t, J = 7.5 Hz, 1H), 7.58 (d, J = ether/ethyl acetate 8:1; saffron yellow solid; yield 67% (140
1
8.2 Hz, 1H), 7.47 (d, J = 8.1 Hz, 3H), 7.32 (s, 1H), 7.29 (s, 1H), mg, 0.34 mmol); mp 170-172 °C; H NMR (300 MHz, CDCl3) δ
2.44 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 191.0, 158.3, 153.8, 8.58 (s, 1H), 8.30 (s, 1H), 8.00 (d, J = 4.2 Hz, 2H), 7.91 (d, J = 8.1
151.6, 142.7, 138.9, 137.1, 133.8, 130.5, 129.9, 128.7, 128.4, Hz, 2H), 7.52-7.47 (m, 4H), 7.45 (s, 1H), 7.31-7.40 (m, 1H), 7.22
126.5, 125.6, 122.5, 119.1, 118.7, 103.1, 90. 8, 21.6; IR (KBr) ν (d, J = 7.8 Hz, 1H), 4.05 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
3034, 3016, 2181, 1647, 1321, 1307, 1249, 817, 775, 765, 754, 191.0, 157.6, 151.5, 149.3, 144.3, 139.0, 137.0, 131.8, 131.3,
744, 686 cm-1; HRMS (APCI) calcd for [C25H16NO2Cl+H]+ 130.6, 129.1, 128.7, 126.6, 125.1, 122.4, 119.9, 117.3, 114.5,
398.0942, found 398.0941.
103.4, 91.3, 56.5; IR (KBr) ν 3231, 3064, 2181, 1614, 1369,
1321, 1246, 831, 735, 704, 688, 671 cm-1; HRMS (APCI) calcd
Petroleum for [C25H16NO3Cl+H]+ 414.0891, found 414.0888.
(Z)-3-(4-Chlorophenyl)-2-(2-(4-methoxyphenyl)-4H-
chromen-4-ylidene)-3-oxopropanenitrile (4nb)
.
ether/ethyl acetate 8:1; saffron yellow solid; yield 72% (149
1
(Z)-3-(4-Chlorophenyl)-2-(2-(4-methoxyphenyl)-6-methyl-
mg, 0.36 mmol); mp 188-190 °C; H NMR (300 MHz, CDCl3) δ 4H-chromen-4-ylidene)-3-oxopropanenitrile (4sb). Petroleum
9.16 (s, 1H), 8.36 (s, 1H), 7.91 (s, 4H), 7.70 (d, J = 5.1 Hz, 1H), ether/ethyl acetate 8:1; saffron yellow solid; yield 69% (156
1
7.57 (d, J = 6.6 Hz, 1H), 7.47 (s, 1H), 7.45 (s, 2H), 6.99 (s, 2H), mg, 0.35 mmol); mp 205-207 °C; H NMR (300 MHz, CDCl3) δ
3.89 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 191.5, 163.1, 158.7, 9.02 (s, 1H), 8.22 (s, 1H), 7.90 (d, J = 6.9 Hz, 4H), 7.65 (d, J = 7.5
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Hz, 1H), 7.43-7.54 (m, 3H), 7.01 (d, J = 8.4 Hz, 2H), 3.90 (s, 3H); 1H), 7.35 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 158.8, 153.1,
13C NMR (125 MHz, CDCl3) δ 190.7, 162.9, 158.2, 151.9, 139.3, 152.6, 134.8, 132.5, 130.4, 129.3, 126.5, 126.3, 125.9, 118.9,
136.8, 133.8, 130.6, 128.8, 128.4, 123.1, 120.0, 114.7, 105.1, 117.8, 116.7, 115.6, 105.0, 103.1, 63.2; IR (KBr) ν 2210, 2200,
102.4, 55.6; IR (KBr) ν 3034, 3008, 2181, 1637, 1323, 1305, 1618, 1255, 1327, 777, 765, 750, 686 cm-1; HRMS (APCI) calcd
1282, 1257, 827, 817, 777, 756, 692 cm-1; HRMS (APCI) calcd for [C18H10N2O+H]+ 271.0866, found 271.0870.
for [C25H15NO2Cl2+H]+ 448.0502, found 448.0506.
(Z)-2-(6-Bromo-2-(4-methoxyphenyl)-4H-chromen-4-
ylidene)-3-(4-chlorophenyl)-3-oxopropanenitrile
2-(2-(p-Tolyl)-4H-chromen-4-ylidene)malononitrile
(5b).
Petroleum ether/ethyl acetate 8:1; yellow solid; yield 72% (102
1
mg, 0.36 mmol); mp 272-274 °C; H NMR (300 MHz, CDCl3) δ
(4tb)
.
Petroleum ether/ethyl acetate 8:1; saffron yellow solid; yield 8.96 (d, J = 8.4 Hz, 1H), 7.86 (d, J = 7.8 Hz, 2H), 7.76 (t, J = 7.5
1
72% (176 mg, 0.36 mmol); mp 194-196 °C; H NMR (300 MHz, Hz, 1H), 7.60 (d, J = 8.1 Hz, 1H), 7.48 (t, J = 7.5 Hz, 1H), 7.35 (d,
CDCl3) δ 9.34 (s, 1H), 8.30 (s, 1H), 7.88 (d, J = 8.1 Hz, 4H), 7.77 J = 7.8 Hz, 2H), 7.31 (s, 1H), 2.46 (s, 3H) ; 13C NMR (125 MHz,
(d, J = 7.8 Hz, 1H), 7.47 (d, J = 8.7 Hz, 2H), 7.42 (s, 1H), 7.00 (d, J CDCl3) δ 159.1, 153.2, 152.5, 143.5, 134.7, 130.0, 127.5, 126.5,
= 8.7 Hz, 2H), 3.89 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 190.7, 126.2, 125.8, 118.8, 117.9, 116.9, 115.8, 102.5, 62.5, 21.7; IR
162.9, 158.1, 152.6, 149.5, 139.2, 136.6, 130.6, 128.8, 128.3, (KBr) ν 2208, 2200, 1618, 1325, 1261, 815, 763, 740, 669 cm-1;
123.2, 121.9, 120.2, 118.5, 114.7, 102.2, 90.8, 55.6; IR (KBr) ν HRMS (APCI) calcd for [C19H12N2O+H]+ 285.1022, found
3034, 3016, 2181, 1643, 1323, 1300, 1244, 850, 819, 763, 744, 285.1018.
686 cm-1; HRMS (APCI) calcd for [C25H15NO3ClBr+H]+ 491.9997,
found 491.9993.
2-(2-(4-Ethylphenyl)-4H-chromen-4-ylidene)malononitrile
(5c). Petroleum ether/ethyl acetate 8:1; yellow solid; yield 75%
1
(112 mg, 0.38 mmol); mp 136-138 °C; H NMR (300 MHz,
(Z)-3-(4-Fluorophenyl)-3-oxo-2-(2-phenyl-4H-chromen-4-
ylidene)propanenitrile (4ac). Petroleum ether/ethyl acetate CDCl3) δ 8.96 (d, J = 8.4 Hz, 1H), 7.88 (d, J = 8.1 Hz, 2H), 7.76 (t,
8:1; yellow solid; yield 65% (121 mg, 0.33 mmol); mp 164-166 J = 7.8 Hz, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.48 (t, J = 7.8 Hz, 1H),
°C; 1H NMR (300 MHz, CDCl3) δ 9.21 (d, J = 7.2 Hz, 1H), 8.26 (s, 7.37 (d, J = 8.1 Hz, 2H), 7.31 (s, 1H), 2.75 (q, J = 7.5 Hz, 2H),
1H), 7.94-8.10 (m, 4H), 7.72 (d, J = 6.9 Hz, 1H), 7.47-7.60 (m, 1.30 (t, J = 7.5 Hz, 3H); 13C NMR (125 MHz, CDCl3) δ 159.1,
5H), 7.20 (s, 1H), 7.16 (d, J = 7.5 Hz, 1H); 13C NMR (125 MHz, 153.1, 152.5, 149. 7, 134.7, 128.9, 127.7, 126.6, 126.2, 125.8,
CDCl3) δ 191.0, 166.0 (d, J = 254.5 Hz), 158.0, 154.1, 151.3, 118.8, 117.8, 116.9, 115.8, 102.5, 62.5, 28.9, 15.2; IR (KBr) ν
135.1, 134.2 ,132.8 (d, J = 9.0 Hz), 132.3, 132.2, 132.1, 131.7, 2210, 2204, 1618, 1263, 815, 761, 742, 711 cm-1; HRMS (APCI)
129.5, 126.8, 126.0, 122.6, 119.5, 119.1, 116.0 (d, J = 22.0 Hz), calcd for [C20H14N2O+H]+ 299.1179, found 299.1176.
103.8, 92.0; IR (KBr) ν 3034, 3020, 2185, 1637, 1319, 1298,
2-(2-(4-Methoxyphenyl)-4H-chromen-4-
1246, 833, 767, 754, 740, 690 cm-1; HRMS (APCI) calcd for ylidene)malononitrile (5d). Petroleum ether/ethyl acetate 8:1;
[C24H14NO2F+H]+ 368.1081, found 368.1099.
yellow solid; yield 73% (109 mg, 0.37 mmol); mp 191-193 °C;
1H NMR (300 MHz, CDCl3) δ 8.96 (d, J = 8.4 Hz, 1H), 7.93 (d, J =
(Z)-3-Oxo-2-(2-phenyl-4H-chromen-4-ylidene)-3-(p-
tolyl)propanenitrile (4ad). Petroleum ether/ethyl acetate 8:1; 8.7 Hz, 2H), 7.75 (t, J = 7.5 Hz, 1H), 7.58 (d, J = 8.1 Hz, 1H), 7.47
yellow solid; yield 69% (145 mg, 0.40 mmol); mp 147-149 °C; (t, J = 7.6 Hz, 1H), 7.25(s,1H), 7.04 (d, J = 8.7 Hz, 1H), 3.92 (s,
1H NMR (300 MHz, CDCl3) δ 9.20 (s, 1H), 8.12 (s, 1H), 7.90 (d, J 3H); 13C NMR (125 MHz, CDCl3) δ 163.2, 158.9, 153.1, 152.5,
= 5.7 Hz, 4H), 7.69 (s, 1H), 7.56 (s, 1H), 7.50 (s, 4H), 7.30 (d, J = 134.6, 128.4, 126.1, 125.9, 122.6, 118.7, 117.9, 117.0, 116.0,
7.8 Hz, 2H), 2.44 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 191.7, 114.8, 101.7, 61.9, 55.7; IR (KBr) ν 2210, 2204, 1618, 1325,
157.0, 153.6, 150.0, 143.9, 135.5, 133.6, 131.5, 131.4, 129.2, 1303, 1261, 835, 763, 740, 665 cm-1; HRMS (APCI) calcd for
129.0, 126.4, 126.3, 125.5, 122.2, 119.1, 118.6, 104.9, 103.4, [C19H12N2O2+H]+ 301.0972, found 301.0971.
92.5, 21.8; IR (KBr) ν 3034, 2189, 1635, 1321, 1280, 1244, 825,
2-(2-(4-Fluorophenyl)-4H-chromen-4-ylidene)malononitrile
788, 765, 752, 688 cm-1; HRMS (APCI) calcd for [C25H17NO2+H]+ (5e). Petroleum ether/ethyl acetate 8:1; yellow solid; yield
364.1332, found 364.1336.
58% (83.5 mg, 0.29 mmol); mp 217-219 °C; 1H NMR (300 MHz,
(Z)-3-(2-Fluorophenyl)-3-oxo-2-(2-phenyl-4H-chromen-4-
CDCl3) δ 8.95 (d, J = 8.1 Hz, 1H), 7.98 (t, J = 6.3 Hz, 3H), 7.78 (t,
ylidene)propanenitrile (4ae). Petroleum ether/ethyl acetate J = 7.5 Hz, 1H), 7.61 (d, J = 8.1 Hz, 1H), 7.5 (t, J = 7.5 Hz, 1H),
8:1; yellow solid; yield 71% (137 mg, 0.36 mmol); mp 127-129 7.25 (s, 1H), 7.22 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 165.6 (d,
1
°C; H NMR (300 MHz, CDCl3) δ 9.16 (s, 1H), 8.37 (s, 1H), 7.95 J = 253.9 Hz), 158.2, 153.3, 152.8, 135.3, 129.2 (d, J = 8.8 Hz),
(d, J = 5.4 Hz, 2H), 7.91 (s, 1H), 7.84 (d, J = 6.9 Hz, 1H), 7.71 (d, J 127.0 (d, J = 3.8 Hz), 126.8, 126.2, 119.2, 118.1, 117.1 (d, J =
= 6.9 Hz, 1H), 7.60 (s, 1H), 7.53 (s, 4H), 7.44 (d, J = 7.5 Hz, 2H); 22.5 Hz), 117.0, 116.0, 103.2, 63.8; IR (KBr) ν 2214, 1602, 1313,
13C NMR (125 MHz, CDCl3) δ 190.8, 157.8, 151.88, 151.3, 1296, 1273, 827, 761, 738, 663 cm-1; HRMS (APCI) calcd for
139.0, 137.0, 135.6, 135.2, 131.7, 131.2, 130.6, 129.1, 128.7, [C18H9N2OF+H]+ 289.0772, found 289.0775.
126.4, 118.6, 118.4, 103.6, 90.9, 21.4; IR (KBr) ν 3066, 3034,
2-(2-(4-Chlorophenyl)-4H-chromen-4-ylidene)malononitrile
2189, 1635, 1321, 1244, 806, 790, 765, 754, 742 cm-1; HRMS (5f). Petroleum ether/ethyl acetate 8:1; yellow solid; yield 62%
(APCI) calcd for [C24H14NO2Cl+H]+ 384.0786, found 384.0784.
2-(2-Phenyl-4H-chromen-4-ylidene)malononitrile (5a)
(94 mg, 0.31 mmol); mp 183-185 °C; 1H NMR (300 MHz, CDCl3)
.
δ 8.97 (d, J = 7.8 Hz, 1H), 7.91 (d, J = 8.1 Hz, 2H), 7.78 (t, J = 6.9
Petroleum ether/ethyl acetate 8:1; yellow solid; yield 70% (94 Hz, 1H), 7.60 (d, J = 8.4 Hz, 1H), 7.52-7.55 (m, 3H), 7.31 (s, 1H);
o
1
mg, 0.35 mmol); mp 175-177 C; H NMR (300 MHz, CDCl3) δ 13C NMR (125 MHz, CDCl3) δ 157.6, 152.8, 152.4, 138.9, 135.0,
8.97 (d, J = 8.4 Hz, 1H), 7.97 (d, J = 6.9 Hz, 2H), 7.78 (t, J = 7.5 129.7, 128.8, 127.7, 126.5, 125.9, 118.9, 117.8, 116.5, 115.5,
Hz, 1H), 7.63 (s, 1H), 7.58 (t, J = 6.9 Hz, 3H), 7.5 (t, J = 7.8 Hz, 103.2, 63.8; IR (KBr) ν 2216, 2208, 1629, 1259, 831, 765, 742,
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669 cm-1; HRMS (APCI) calcd for [C18H9N2OCl+H]+ 305.0476, yellow solid; yield 71% (113 mg, 0.36 mmol); mp 136 - 139 °C;
found 305.0479.
1H NMR (300 MHz, CDCl3) δ 8.74 (s, 1H), 7.95 (d, J = 6.0 Hz,
2-(2-(4-Bromophenyl)-4H-chromen-4-ylidene)malononitrile 2H), 7.49-7.56 (m, 4H), 7.31 (s, 1H), 2.50 (s, 3H); 13C NMR (125
(5g). Petroleum ether/ethyl acetate 8:1; yellow solid; yield 62% MHz, CDCl3) δ 158.7, 153.0, 150.8, 136.5, 136.1, 132.4, 130.5,
1
(108 mg, 0.31 mmol); mp 221-223 °C; H NMR (300 MHz, 129.3, 126.5, 125.2, 118.6, 117.6, 116.9, 115.8, 103.0, 62.6,
CDCl3) δ 8.96 (d, J = 7.9 Hz, 1H), 7.90 (d, J = 7.8 Hz, 2H), 7.79 (t, 21.4; IR (KBr) ν 2208, 2196, 1618, 1313, 1280, 1259, 819, 775,
J = 7.5 Hz, 1H), 7.60 (d, J = 8.4 Hz, 2H), 7.53 (d, J = 7.2 Hz, 2H), 690, 669 cm-1; HRMS (APCI) calcd for [C19H11N2OCl+H]+
7.30 (s, 1H); 13C NMR (125 MHz, CDCl3) δ 157.6, 152.8, 152.4, 319.0633, found 319.0637.
138.9, 135.0, 132.7, 129.7, 128.8, 127.7, 126.5, 125.9, 118.8,
2-(2-(4-Bromophenyl)-6-methyl-4H-chromen-4-
117.7, 116.5, 115.5, 103.2, 63.9; IR (KBr) ν 2216, 2204, 1627, ylidene)malononitrile (5m). Petroleum ether/ethyl acetate
1257, 831, 765, 742, 669 cm-1; HRMS (APCI) calcd for 8:1; yellow solid; yield 72% (130 mg, 0.36 mmol); mp 237-239
[C19H11N2OBr+H]+ 348.9971, found 348.9965.
°C; 1H NMR (300 MHz, CDCl3) δ 8.75 (s, 1H), 7.67-7.83 (m, 4H),
2-(2-(2-Fluorophenyl)-4H-chromen-4-ylidene)malononitrile 7.48-7.60 (m, 2H), 7.29 (s, 1H), 2.50 (s, 3H); 13C NMR (125 MHz,
(5h). Petroleum ether/ethyl acetate 8:1; yellow solid; yield CDCl3) δ 157.6, 152.7, 150.7, 136.7, 136.2, 132.6, 129.4, 127.8,
1
64% (92 mg, 0.32 mmol); mp 183-185 °C; H NMR (300 MHz, 127.2, 125.3, 118.5, 117.5, 116.6, 115.7, 103.1, 63.3, 21.4; IR
CDCl3) δ 8.95 (d, J = 7.5 Hz, 1H), 7.93 (s, 1H), 7.77 (s, 1H), 7.58 (KBr) ν 2212, 2200, 1624, 1313, 1300, 1261, 854, 827, 750, 719
(d, J = 7.2 Hz, 2H), 7.50 (s, 2H), 7.35 (t, J = 6.3 Hz, 1H), 7.23 (s, cm-1; HRMS (APCI) calcd for [C19H11N2OBr+H]+ 363.0128, found
1H); 13C NMR (125 MHz, CDCl3) δ 161.1 (d, J = 255.1 Hz, 1H), 363.0131.
154.6, 153.2, 153.0, 135.3, 134.1 (d, J = 8.8 Hz, 3H), 129.4,
2-(6-Methoxy-2-phenyl-4H-chromen-4-
126.8, 126.2,125.3 (d, J = 3.8 Hz, 2H), 119.5, 119.2, 118.0, ylidene)malononitrile (5n). Petroleum ether/ethyl acetate 8:1;
117.6 (d, J = 22.5 Hz, 2H) 116.9, 115.6, 108.0, 107.9, 64.8; IR yellow solid; yield 74% (111 mg, 0.37 mmol); mp 200-202 °C;
(KBr) ν 2212, 2200, 1618, 1303, 1251, 767, 758, 740, 713 cm-1; 1H NMR (300 MHz, CDCl3) δ 8.41 (s, 1H), 7.96 (d, J = 7.8 Hz,
HRMS (APCI) calcd for [C18H9N2OF+H]+ 289.0772, found 2H), 7.52-7.59 (m, 4H), 7.38 (d, J = 7.8 Hz, 1H), 7.34 (s, 1H),
289.0780.
3.94 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 158.7, 157.2, 153.2,
2-(6-Methyl-2-phenyl-4H-chromen-4-ylidene)malononitrile 147.4, 132.4, 130.5, 129.3, 126.4, 124.9, 120.0, 118.4, 117.2,
(5i). Petroleum ether/ethyl acetate 8:1; saffron yellow solid; 115.9, 105.6, 102.7, 56.1; IR (KBr) ν 2999, 2204, 2189, 1608,
o
1
yield 77% (109 mg, 0.38 mmol); mp 220-222 C; H NMR (300 1309, 1251, 837, 773, 690, 648 cm-1; HRMS (APCI) calcd for
MHz, CDCl3) δ 8.76 (s, 1H), 7.96 (d, J = 6.9 Hz, 2H), 7.43-7.66 [C19H12N2O2+H]+ 301.0972, found 301.0977.
(m, 4H), 7.33 (s, 1H), 2.51 (s, 3H); 13C NMR (125 MHz, CDCl3) δ
2-(6-Methoxy-2-(p-tolyl)-4H-chromen-4-
158.7, 153.0, 150.9, 136.5, 136.1, 132.4, 130.5, 129.3, 126.5, ylidene)malononitrile (5o). Petroleum ether/ethyl acetate 8:1;
125.3, 118.6, 117.6, 116.9, 115.8, 103.0, 62.7, 21.4; IR (KBr) ν yellow solid; yield 66% (104 mg, 0.33 mmol); mp 195-197 °C;
2208, 2196, 1618, 1334, 1313, 1261, 821, 775, 690, 648 cm-1; 1H NMR (300 MHz, CDCl3) δ 8.37 (s, 1H), 7.82 (d, J = 7.5 Hz,
HRMS (APCI) calcd for [C19H12N2O+H]+ 285.1022, found 2H), 7.52 (d, J = 9.0 Hz, 1H), 7.32 - 7.34 (m, 3H), 7.25 (s, 1H),
285.1029.
2-(2-(4-Methoxyphenyl)-6-methyl-4H-chromen-4-
3.91 (s, 3H), 2.45 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 158.9 ,
157.1, 153.2, 147.3, 143.3, 130.0, 128.4, 127.6, 126.4, 124.7,
ylidene)malononitrile (5j). Petroleum ether/ethyl acetate 8:1; 120.0, 118.4, 117.3, 116.0, 105.6, 102.0, 61.3, 56.1, 21.7; IR
yellow solid; yield 71% (111 mg, 0.36 mmol); mp 187-189 °C; (KBr) ν 2212, 2196, 1620, 1309, 1251, 817, 810, 738, 709 cm-1;
1H NMR (300 MHz, CDCl3) δ 8.70 (s, 1H), 7.89 (d, J = 8.1 Hz, HRMS (APCI) calcd for [C20H14N2O2+H]+ 315.1128, found
2H), 7.45-7.56 (m, 2H), 7.18 (s, 1H), 7.01 (d, J = 8.4 Hz, 2H), 315.1121.
3.91 (s, 3H), 2.48 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 141.8,
2-(2-(4-Fluorophenyl)-6-methoxy-4H-chromen-4-
137.4, 131.6, 129.4, 115.0, 114.5, 107.0, 103.9, 101.3, 97.1, ylidene)malononitrile (5p). Petroleum ether/ethyl acetate 8:1;
96.2, 95.8, 94.8, 93.4, 80.2, 39.9, 34.3; IR (KBr) ν 2208, 2196, yellow solid; yield 63% (102 mg, 0.32 mmol); mp 223-225 °C;
1616, 1298, 1269, 831, 821, 765, 750 cm-1; HRMS (APCI) calcd 1H NMR (300 MHz, CDCl3) δ 8.41 (d, J = 7.5 Hz, 1H), 7.995-
for [C20H14N2O2+H]+ 315.1128, found 315.1129.
8.007 (m, 2H), 7.52-7.57 (m, 1H), 7.35-7.39 (m, 2H), 7.27 (s,
1H), 7.23 (d, J = 8.4 Hz, 1H), 3.94 (s, 3H); 13C NMR (125 MHz,
2-(2-(4-Fluorophenyl)-6-methyl-4H-chromen-4-
ylidene)malononitrile (5k). Petroleum ether/ethyl acetate 8:1; CDCl3) δ 157.7, 157.3, 153.1, 147.3, 129.5, 128.8 (d, J = 8.8 Hz),
yellow solid; yield 66% (100 mg, 0.33 mmol); mp 221-223 °C; 125.0, 120.0, 118.3, 117.1, 116.7 (d, J = 22.1 Hz), 105.7, 105.0,
1H NMR (300 MHz, CDCl3) δ 8.73 (s, 1H), 7.96 (s, 2H), 7.48- 102.5, 95.1, 56.2; IR (KBr) ν 2216, 2196, 1624, 1319, 1296,
7.60(m, 2H), 7.24 (s, 2H), 7.21(s,1H), 2.49 (s, 3H); 13C NMR (125 1253, 835, 819, 777, 738 cm-1; HRMS (APCI) calcd for
MHz, CDCl3) δ 165.2 (d, J = 255.2 Hz), 157.7, 152.8, 150.7, [C19H11N2O2F+H]+ 319.0877, found 319.0979.
136.7, 136.2, 128.8 (d, J = 9.0 Hz), 126.7 (d, J = 2.9 Hz, 5H),
2-(8-Methoxy-2-phenyl-4H-chromen-4-
125.2, 118.5, 117.5, 116.7 (d, J = 22.2 Hz), 115.8, 102.7, 62.8, ylidene)malononitrile (5q). Petroleum ether/ethyl acetate 8:1;
21.4; IR (KBr) ν 2216, 2196, 1624, 1319, 1286, 1238, 835, 819, yellow solid; yield 68% (102 mg, 0.34 mmol); mp 209-211 °C;
771, 750 cm-1; HRMS (APCI) calcd for [C19H11N2OF+H]+ 1H NMR (300 MHz, CDCl3) δ 8.50 (d, J = 8.2 Hz, 1H), 8.00-8.03
303.0928, found 303.0930.
(m, 2H), 7.56 (d, J = 7.2 Hz, 2H), 7.37-7.43 (m, 2H), 7.27 (s, 1H),
7.25 (s, 1H), 4.05 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 158.7,
2-(2-(4-Chlorophenyl)-6-methyl-4H-chromen-4-
ylidene)malononitrile (5l). Petroleum ether/ethyl acetate 8:1; 157.2, 153.2, 147.4, 132.4, 130.5, 129.3, 126.4, 125.0, 120.0,
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118.4, 117.2, 115.9, 105.6, 102.7, 62.0, 56.2; IR (KBr) ν 2214,
(Z)-Ethyl-2-cyano-2-(2-phenyl-4H-chromen-4-
2200, 1625, 1321, 1307, 1230, 790, 767, 727, 711, 678 cm-1; ylidene)acetate (5w). Petroleum ether/ethyl acetate 8:1;
HRMS (APCI) calcd for [C19H12N2O2+H]+ 301.0972, found yellow solid; yield 70% (111 mg, 0.35 mmol); mp 160-162 °C;
301.0980.
2-(2-(4-Fluorophenyl)-8-methoxy-4H-chromen-4-
1H NMR (300 MHz, CDCl3) δ 9.10 (d, J = 8.4 Hz, 1H), 8.90 (s,
1H), 7.91 (dd, J = 4.4, 3.4 Hz, 2H), 7.61 (dd, J = 11.3, 4.1 Hz, 1H),
ylidene)malononitrile (5r). Petroleum ether/ethyl acetate 8:1; 7.35-7.59 (m, 5H), 7.19 (s, 1H), 4.28 (q, J = 7.1 Hz, 2H), 1.34 (t, J
yellow solid; yield 76% (114 mg, 0.38 mmol); mp 178-180 °C; = 7.1 Hz, 3H); 13CNMR (125 MHz, CDCl3) δ 165.8, 157.6, 153.8,
1H NMR (300 MHz, CDCl3) δ 7.43-7.67 (m, 2H), 7.29 (s, 2H), 151.8, 133.9, 132.0, 131.8, 129.4, 127.2, 126.8, 125.8, 120.9,
7.21 (d, J = 9.0 Hz, 2H), 7.09 (s, 1H), 7.02 (d, J = 6.9 Hz, 1H), 119.2, 118.9, 103.3, 84.5, 77.6, 77.4, 77.1, 61.7, 14.7; IR (KBr) ν
4.09 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 164.8 (d, J = 252.8 2218, 1728, 1248, 915, 845, 753, 738 cm-1; HRMS (APCI) calcd
Hz), 156.8, 150.4, 146.7, 145.9, 132.0 (d, J = 8.9 Hz), 129.1, for [C20H15NO3+H]+ 318.1085, found 318.1089.
125.4, 120.6, 120.5, 116.5 (d, J = 22.1 Hz), 114.8, 113.7 (d, J =
(Z)-Ethyl-2-cyano-2-(2-(4-ethylphenyl)-4H-chromen-4-
2.5 Hz), 113.2, 112.3, 112.2, 79.7, 57.0; IR (KBr) ν 2222, 1560, ylidene)acetate (5x). Petroleum ether/ethyl acetate 8:1;
1305, 1232, 806, 775, 729, 707, 669 cm-1; HRMS (APCI) calcd yellow solid; yield 56% (96 mg, 0.28 mmol); mp 178-180 °C; 1H
for [C19H11N2OF+H]+ 301.0972, found 301.0980.
NMR (300 MHz, CDCl3) δ 9.11 (d, J = 8.4 Hz, 1H), 8.89 (s, 1H),
7.84 (d, J = 8.1 Hz, 2H), 7.62 (t, J = 7.5 Hz, 1H), 7.47 (d, J = 8.1
2-(6-Chloro-2-(p-tolyl)-4H-chromen-4-
ylidene)malononitrile (5s). Petroleum ether/ethyl acetate 8:1; Hz, 1H), 7.37 (t, J = 7.8 Hz, 1H), 7.28 (s, 1H), 7.19 (s, 1H), 4.28
yellow solid; yield 64% (101 mg, 0.32 mmol); mp 197-199 °C; (q, J = 14.2, 7.1 Hz, 2H), 2.66 (q, J = 15.1, 7.5 Hz, 2H), 1.34 (t, J =
1H NMR (300 MHz, CDCl3) δ 8.91 (d, J = 7.2 Hz, 1H), 7.82 (d, J = 7.2 Hz, 3H), 1.21 (t, J = 7.5 Hz, 3H); 13CNMR (125 MHz, CDCl3) δ
8.1 Hz, 2H), 7.68-7.72 (m, 1H), 7.55 (d, J = 9.0 Hz, 1H), 7.36 (s, 166.0, 158.0, 153.8, 152.1, 149.0, 133.9, 129.3, 129.0, 127.2,
1H), 7.33 ( s, 1H), 7.27 (s, 1H), 2.46 (s, 3H); 13C NMR (125 MHz, 126.9, 125.8, 121.2, 119.3, 119.0, 102.9, 83.8, 61.7, 29.3, 15.7,
CDCl3) δ 159.1, 151.6, 151.0, 143.8, 134.9, 131.8, 130.1, 127.1, 14.8; IR (KBr) ν 2218, 1728, 1248, 901, 856, 833, 727 cm-1;
126.4, 125.1, 118.8, 116.2, 115.3, 106.8, 102.3, 63.5, 21.7; IR HRMS (APCI) calcd for [C22H19NO3+H]+ 346.1365, found
(KBr) ν 2212, 2204, 1614, 1303, 1292, 1257, 831, 821, 738, 715 346.1369.
cm-1; HRMS (APCI) calcd for [C19H11N2OCl+H]+ 318.0871, found
318.0876.
(Z)-Ethyl-2-(2-(4-chlorophenyl)-4H-chromen-4-ylidene)-2-
cyanoacetate (5y). Petroleum ether/ethyl acetate 8:1; yellow
1
solid; yield 50% (87 mg, 0.25 mmol); mp 194-196 °C; H NMR
2-(6-Bromo-2-phenyl-4H-chromen-4-ylidene)malononitrile
(5t). Petroleum ether/ethyl acetate 8:1; yellow solid; yield 63% (300 MHz, CDCl3) δ 1.42 (t, J = 15.0 Hz, 3H), 4.35 (dd, J = 12Hz,
1
(109 mg, 0.32 mmol); mp 267-269 °C; H NMR (300 MHz, J=12.0 Hz, 2H), 7.48-7.70 (m, 5H), 7.92 (d, J = 12.0 Hz, 2H),
CDCl3) δ 9.10 (s, 1H), 7.95 (d, J = 7.2 Hz, 2H), 7.84 - 7.87(m, 1H), 8.96(s, 1H), 9.18(d, J = 9.0 Hz, 1H); 13CNMR (125 MHz, CDCl3):
7.56-7.61 (m, 3H), 7.49-7.52 (m, 1H), 7.34 (s, 1H); 13C NMR δ165.7, 156.4, 153.7, 151.6, 138.2, 134.0, 130.3, 129.7, 128.0,
(125 MHz, CDCl3) δ 158.8, 151.5, 151.4, 137.8, 132.7, 130.0, 127.2, 126.0, 120.7, 119.1, 118.9, 103.3, 84.9, 77.6, 77.4, 77.1,
129.4, 128.3, 126.5, 120.5, 119.4, 116.0, 115.1, 103.1, 64.4; IR 61.8, 14.7; IR (KBr) ν 2217, 1728, 1248, 889, 845, 817, 749 cm-
(KBr) ν 3034, 3012, 2208, 2200, 1610, 1307, 1298, 1257, 825, 1; HRMS (APCI) calcd for [C20H14ClNO3+H]+ 352.0633, found
775, 748, 688 cm-1; HRMS (APCI) calcd for [C18H9N2OBr+H]+ 352.0.660.
348.9971, found 348.9973.
(Z)-Ethyl-2-cyano-2-(6-methyl-2-phenyl-4H-chromen-4-
2-(6-Bromo-2-(p-tolyl)-4H-chromen-4-
ylidene)acetate (5z). Petroleum ether/ethyl acetate 8:1;
ylidene)malononitrile (5u). Petroleum ether/ethyl acetate 8:1; yellow solid; yield 60% (99 mg, 0.30 mmol); mp 165-167 °C; 1H
yellow solid; yield 65% (119 mg, 0.33 mmol); mp 205-207 °C; NMR (300 MHz, CDCl3) δ 8.97 (d, J = 4.5 Hz, 2H), 7.98 (dd, J =
1H NMR (300 MHz, CDCl3) δ 9.07 (s, 1H), 7.83 (d, J = 7.5 Hz, 6.3 Hz, 3.0 Hz, 2H), 7.43-7.52 (m, 5H), 4.35 (q, J = 7.2 Hz, 2H),
3H), 7.49 (d, J = 8.8 Hz, 2H), 7.35 (d, J = 7.8 Hz, 2H), 7.28 (s, 2.50 (s, 3H), 1.42 (t, J = 7.2 Hz, 3H); 13CNMR (125 MHz, CDCl3) δ
1H), 2.46 (s, 3H); 13C NMR (125 MHz, CDCl3) δ 159.0, 151.4, 165.9, 157.9, 153.8, 152.1, 149.0, 133.8, 129.2, 129.0, 127.2,
143.8, 137.7, 130.1, 128.2, 127.1, 126.5, 120.5, 119.2, 116.2, 126.9, 125.8, 121.2, 119.3, 118.9, 102.9, 83.8, 77.7, 77.4, 77.2,
115.3, 105.0, 102.5, 63.6, 21.71; IR (KBr) ν 2212, 2196, 1614, 61.7, 29.3, 15.7, 14.8; IR (KBr) ν 2218, 1728, 1248, 891, 854,
1305, 1292, 1255, 823, 813, 717, 671 cm-1; HRMS (APCI) calcd 813, 726 cm-1; HRMS (APCI) calcd for [C21H17NO3+H]+ 332.1208,
for [C19H11N2OBr+H]+ 363.0128, found 363.0125.
found 332.1213.
2-(6,8-Di-tert-butyl-2-phenyl-4H-chromen-4-
ylidene)malononitrile (5v). Petroleum ether/ethyl acetate 8:1;
yellow solid; yield 78% (149 mg, 0.39 mmol); mp 213-215 °C;
1H NMR (300 MHz, CDCl3) δ 8.86 (d, J = 6.9 Hz, 1H), 7.99-
8.01(m, 2H), 7.82 (d, J = 6.9 Hz, 1H), 7.57-7.59 (m, 3H), 7.40 (s,
1H), 1.59 (s, 9H), 1.41 (s, 9H); 13C NMR (125 MHz, CDCl3) δ
159.0, 151.4, 143.8, 137.7, 130.1, 128.2, 127.1, 126.5, 120.5,
119.2, 116.2, 115.3, 105.0 102.5, 63.6, 21.7; IR (KBr) ν 2208,
2193, 1624, 1309, 1290, 1253, 848, 813, 763, 680 cm-1; HRMS
(APCI) calcd for [C26H26N2O+H]+ 383.2118, found 383.2120.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
The work was partially supported by the National Natural
Science Foundation of China (Nos. 21772001, 21372008), the
Anhui Provincial Natural Science Foundation (No.
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Mandal, and C. J. Lovely, Bioorg. Med. Chem., 2017, 25
1608-1621.
,
1808085MB41), the Natural Science Foundation of Education
Administration of Anhui Province (No. KJ2016A267), the
Special and Excellent Research Fund of Anhui Normal
University, and the Doctoral Scientific Research Foundation of
Anhui Normal University (No. 2016XJJ110).
7
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