Synthesis of coumarins via PIDA/I2-mediated oxidative cyclization of substituted phenylacrylic acids

Article abstract of DOI:10.1039/c3ra23188g

A variety of functionalized coumarins were synthesized from substituted phenylacrylic acids via PIDA/I₂-mediated and irradiation-promoted oxidative carbon-oxygen bond formation. Our studies show that the oxygen in the pendant carboxylic acid group cyclizes favorably to the aryl ring that is cis to it. The main advantages of this method include good functional group tolerance and the transition-metal-free characteristic. The Royal Society of Chemistry 2013.

Full text of DOI:10.1039/c3ra23188g

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Synthesis of coumarins via PIDA/I2-mediated oxidative
cyclization of substituted phenylacrylic acids3
Cite this: RSC Advances, 2013, 3,
4311
Jinming Li, Huiyu Chen, Daisy Zhang-Negrerie, Yunfei Du* and Kang Zhao*
A variety of functionalized coumarins were synthesized from substituted phenylacrylic acids via PIDA/I2-
mediated and irradiation-promoted oxidative carbon–oxygen bond formation. Our studies show that the
oxygen in the pendant carboxylic acid group cyclizes favorably to the aryl ring that is cis to it. The main
advantages of this method include good functional group tolerance and the transition-metal-free
characteristic.
Received 5th December 2012,
Accepted 17th January 2013
DOI: 10.1039/c3ra23188g
www.rsc.org/advances
protected hydroxy group at the ortho-position with various
arylboronic acids (Fig. 2, path g).10 In addition to the above
Introduction
strategies, some other methods4,11 have also been developed to
access this important scaffold. What’s in common among the
existing approaches is that the oxygen connected to the aryl
ring comes from the phenol derivatives, which means this
O-atom is installed to the aryl ring in the early stage of the
synthetic route. In this paper, we report an alternative
approach to access the 4-aryl coumarin skeletons, in which a
pendant oxygen in the carboxylic acid moiety in phenylacrylic
acid derivatives as the starting material is annulated to the
benzene ring through oxidative carbon–oxygen bond forma-
tion (Fig. 2, path h). To our knowledge, the method described
herein, differing from all existing approaches, represents the
first synthesis of 4-aryl coumarins that does not use phenol
derivatives as starting materials.
Coumarin and its derivatives are widely distributed in natural
products.1 Among the naturally occurring products, 4-aryl
coumarin derivatives, also known as neoflavonoids, have
received considerable attention after they were reported to
show important biological properties2 such as cytotoxic,3a anti-
HIV,3b antibacterial,3c and antimalarial activities3d (for repre-
sentative examples, see Fig. 1).
To date, many synthetic methods have been developed for
the formation of 4-aryl coumarin compounds.4–10 Most of the
currently known strategies fall into one of the following
categories, differing from each other in the starting materials:
(1) condensation of phenols with esters of arylacetic acids (the
Pechmann reaction) (Fig. 2, path a);4 (2) reactions starting
from substituted o-hydroxybenzophenones, utilizing the well-
known Perkin reaction, Wittig reaction or Knoevenagel-type
condensation reaction (Fig. 2, path b).4,5 (3) Ester formation
from propargylic acid derivatives, followed by intramolecular
annulation, with the exception that aryl 3-phenylpropiolate
was reported to also undergo direct cyclization mediated by
catalysts to give 4-aryl coumarin compounds (Fig. 2, path c).6
(4) Dehydrogenation of 3,4-dihydrocoumarin in the presence
of iodine or Pd/C (Fig. 2, path d).4,7 (5) Arylation of coumarins
at 4-positions using organometallic reagents or arylboronic
acids (Fig. 2, path e).4,8 (6) A domino reaction between 3-
(o-hydroxyaryl)acrylates and aryl iodides or bromides involving
Pd-mediated allylic arylation and the subsequent lactonization
(Fig. 2, path f).9 (7) Cu-mediated hydroarylation of methyl
phenylpropiolates containing a methoxy-methyl-ether (MOM)-
Owing to their superb oxidizing properties and low toxicity
compared with classic heavy-metal oxidants, hypervalent
iodine(III) reagents have recently been widely applied to form
carbon–carbon bonds as well as construct heterocyclic
compounds through carbon–heteroatom and heteroatom–
heteroatom bond formation.12 Several novel methods have
been developed for the synthesis of lactones using hypervalent
iodine reagents,13 which realizes the oxidative bond formation
Tianjin Key Laboratory for Modern Drug Delivery & High-Efficiency, School of
Pharmaceutical Science and Technology, Tianjin University, Tianjin 300072, P. R.
China. E-mail: duyunfeier@tju.edu.cn; kangzhao@tju.edu.cn;
Fax: +86-22-27404031; Tel: +86-22-27404031
Electronic supplementary information (ESI) available: NMR data. CCDC
3
Fig. 1 Representative examples of some naturally occurring 4-arylcoumarin
911557. For ESI and crystallographic data in CIF or other electronic format see
DOI: 10.1039/c3ra23188g
products.
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Table 1 Optimization of the reaction conditionsa
Additive
(equiv.)
Solvent
(conc.)
Time Yieldb
Entry Oxidant
(h)
(%)
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
PIFA
PIDA
BF3?Et2O (1.5) TFA (0.2)
BF3?Et2O (1.5) TFA (0.2)
6
6
24
24
6
NDc
NDc
ND/NDc
ND/NDc
20
PIDA or PIFA TFA (0.5)
PIDA or PIFA LiBr (0.5)
PIFA
PIDA
—
PIDA
PIDA
PIDA
PIDA
PIDA
PIDA
PIDA
PIDA
DCM (0.2)
DCM (0.2)
DCM (0.2)
DCM (0.2)
DCM (0.2)
DCM (0.1)
DCM (0.05)
DCM (0.05)
DCM (0.05)
toluene (0.05)
DMF (0.05)
CH3CN (0.05)
EtOH (0.05)
I2 (0.2)
I2 (0.2)
I2 (0.2)
I2 (0.2)
I2 (0.2)
I2 (0.2)
I2 (0.2)
I2 (0.2)
I2 (0.2)
I2 (0.2)
I2 (0.2)
Fig. 2 Representative strategies for the construction of the 4-aryl coumarin
6
46
NDc
79
skeleton.
12
12
8
8
2
6
6
6
6
90
71d
between the oxygen of the carboxylic acid moiety and the
aromatic sp2-carbon or the benzylic sp3-carbon. For example,
Yokoyama and coworkers reported that oxidative cyclization of
o-alkyl or o-arylaromatic acids with hypervalent iodine reagent
or simply iodine gave the corresponding lactones under
92e
56
NRf
NRf
NRf
a
Conditions: 1a (0.2 mmol), I(III) oxidant (0.3 mmol) and additive in
irradiation with
a
high-pressure mercury lamp.14 Upon
solvent (4 mL) stirred at rt. Isolated yields. c No desired product was
b
detected. d The reaction was carried out at 50 uC. e The reaction was
treatment with phenyliodine(III) bistrifluoroacetate (PIFA) or
phenyliodine diacetate (PIDA), the para-substituted phenol or
phenol ether derivatives bearing a side-chain containing a
terminal carboxylic acid moiety underwent oxidative cycliza-
tion to give spiro dienone lactones.15 Most recently, Gu and co-
workers reported the synthesis of 3,4-dihydrocoumarins
through oxidative cyclization of either electron-neutral or
electron-deficient 3-arylpropionic acids with PIFA in the
presence of BF3?Et2O in TFA.16 Inspired by the above
transformations, we envisioned a similar aromatic C–O bond
formation which would eventually lead to coumarin com-
pounds if phenylacrylic acid derivatives were subjected to
certain oxidative conditions mediated by the hypervalent
iodine reagent.
irradiated with a tungsten lamp (200 W) at rt. f No reaction occurred.
favorable conditions including using TFA and LiBr as additives
and DCM as solvent yielded no successful result. Inspired by
Yokoyama’s lactonization methods14 in which molecular
iodine was used as catalyst, we treated substrate 1a with
PIFA in the presence of 0.2 equivalent of iodine in DCM. To
our delight, the reaction afforded the desired cyclized 2a in
20% yield, with the formation of a decarboxylated and
iodinated byproduct, i.e. (2-iodoethene-1,1-diyl)dibenzene ,in
15% yield and some other unidentified byproducts (Table 1,
entry 5). When PIDA was used in place of PIFA, the reaction
became much cleaner and the desired product was separated
and amounted to an improved yield of 46%. A control
experiment showed that no desired coumarin product was
formed in the absence of PIDA or PIFA if solely iodine was
used as the oxidant (Table 1, entry 7). Our further studies of
condition-screening showed that the yield of product 2a
dramatically increased as the concentration of substrate 1a
in CH2Cl2 decreased (Table 1, entries 6, 8, 9). Particularly,
when the reaction mixture was diluted to 0.05 M, the cyclized
product 2a was obtained in 90% yield, with the formation of
only a trace amount of the decarboxylated and iodinated
byproducts (Table 1, entry 9), even though the reaction needed
relatively longer reaction time (8 h). On the other hand, an
attempt to accelerate the reaction rate by raising the
temperature to 50 uC turned out to be unsuccessful due to
the formation of more byproducts under these conditions
(Table 1, entry 10). However, much to our delight, when the
reaction was irradiated with a tungsten lamp (200 W) at room
temperature, the reaction went to completion within 2 h and
Result and discussion
We selected the readily available cinnamic acid and subjected
it to the identical oxidative conditions (PIFA, BF3?Et2O, TFA)
described by Gu16 as our initiative test of the feasibility of the
reaction. However, no desired cyclized coumarin product was
obtained, which indicated that the trans- configuration in the
substrate, not to isomerize to the cis configuration during the
reaction, prevented the cyclization from occurring. To get
around the configuration problem, phenylacrylic acid 1a was
then chosen as the substrate for further study as cyclization
between the oxygen in the pendant carboxylic acid group and
the cis-phenyl ring can be naturally expected. However, the
reaction gave a complex mixture and the expected 4-aryl
coumarin 2a was not formed under the mentioned conditions.
No desired product was formed either after replacing PIFA
with the less potent PIDA. Further explorations of more
4312 | RSC Adv., 2013, 3, 4311–4320
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Table 2 Scope of substituted substrates in PIDA/I2-mediated coumarin synthe-
sisa
Table 2 (Continued)
Entry Substrate 1
Product 2
Time (h) Yieldb(%)
Entry Substrate 1
Product 2
Time (h) Yieldb(%)
8
3
67
1
2
92
9c
3
75c
2
3
4
5
2
81
10
11
8
7
61
65
4
6
82
68
46
12
10
59
24
13
12
76
43
85
6
7
4
4
84
78
14d
3
15
2
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Table 2 (Continued)
Entry Substrate 1
Product 2
Time (h) Yieldb(%)
16e
ND
8
0
Fig. 3 X-ray crystal structure of 2f.
17f,g
30
12
41
0
during the reaction process, while the other substituents
included in this study do not display this effect. For substrates
bearing an electron-withdrawing cyano group on the phenyl
ring, no isomerized byproduct was observed in either case
(Table 2, entries 10–11). When a phenylacrylic acid bearing a
nitro group was used, the reaction needs a much longer time
and a lower yield of cyclized product was obtained (Table 2,
entry 12). Further investigation revealed that the reaction was
also applicable to the synthesis of highly substituted 4-aryl
coumarins (Table 2, entry 14). Moreover, the method can be
further extended to the preparation of 4-methyl coumarin
compounds (Table 2, entry 15).
Some substituted cinnamic acids were explored to further
study whether the isomerization of the double bond may occur
and therefore allow the cyclization. Disappointingly, neither
substrate (E)-1p or (Z)-1r was converted to the cyclized product
under the same conditions (Table 2, entry 16). However, to our
delight, a 41% yield of the cyclized 2q was obtained17 if the
reaction was conducted using 3.0 equivalent of PIDA and 0.5
equivalent of iodine in DCE under reflux for 30 h (Table 2,
entry 17).
18g
ND
a
Optimal conditions: substrate 1 (0.2 mmol), PIDA (0.3 mmol), I2
(0.04 mmol) in CH2Cl2, irradiation with a tungsten lamp (200 W) at
rt, unless otherwise stated. Isolated yields. Trace of 2h was
detected. 0.4 equiv. of I2 was used for a complete reaction. No
reaction occurred at room temperature; when stirred at reflux in
DCE, no desired product was detected. The reaction was carried
out using 3.0 equiv. of PIDA and 0.6 equiv. of I2 under fluorescent
light (40 W). DCE was used as solvent, reflux.
b
c
d
e
f
g
yielded the product in an excellent 92% yield (Table 1, entry
11). Finally, our solvent study shows that toluene was inferior
to CH2Cl2 while the other solvents including DMF, CH3CN and
EtOH prevented this conversion from taking place (Table 1,
entries 12–15).
We initiated our investigation of the scope of substituents
by firstly exploring the symmetrically substituted diaryl acrylic
acids. It was found that the reaction could tolerate various
substituents, such as methyl, chloro and bromo groups and
afforded the corresponding 4-aryl coumarin in acceptable to
good yields (Table 2, entries 2–4). Notably, even the substrate-
bearing nitro groups underwent the same reaction and yielded
the cyclized product 2e, albeit in a lower yield (Table 2, entry
5), along with much longer time and an excess dosage of both
PIDA and iodine.
When an unsymmetrically diphenyl substituted acrylic
acid, i.e. (Z)-1f, was applied, the oxygen atom of the carboxylic
acid cyclized to the adjacent chloro-substituted phenyl ring
(Table 2, entry 6). This result is consistent with our earlier
finding of the configuration requirement of this reaction.
Similarly, the cyclization of the opposite isomer (E)-1g resulted
in the formation of 2g Table 2, entry 7). The reaction involving
the bromo-substituted 1h and 1i displays similar cyclization
selectivity, but with trace formation (5%) of the other isomer
2h in the case of (E)-1i (Table 2, entry 9). We tentatively
propose that the presence of bromo in (E)-1i facilitates the
isomerization of the double bond via a conjugation effect
In addition to the spectroscopic data, X-ray crystallography
of the colorless crystal of 2f (shown in Fig. 3) was obtained,
which unambiguously confirmed the structure of the cou-
marin products.
Two unexpected reactions were observed associated with
the symmetrically substituted diaryl acrylic acids 1s in which a
methoxy group is substituted on either of the two phenyl rings.
When 1s was subjected to the mentioned conditions (1.5
equiv. of PIDA, 0.5 equiv. of I2, hv), no cyclization took place,
but rather, a decarboxylated and iodinated product 3 was
separated as the major product (see Scheme 1).18 We postulate
here that the electron-donating methoxy groups on the phenyl
rings facilitate the electrophilic iodination of the double bond
via conjugation, followed by decarboxylation and gave 3.
Scheme 1 Formation of iodinated compound 3 and diphenylethylene 4 from
1s.
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ppm and referred to the internal standard of TMS set as 0.00
ppm. The peak patterns are indicated as follows: s, singlet; d,
doublet; t, triplet; q, quadruplet; m, multiplet; br, broad and
dd, doublet of doublets. The coupling constants J, are reported
in Hertz (Hz). High-resolution mass spectra (HRMS) were
obtained on a Q-TOF micro spectroMeter. Melting points were
determined with a micro melting-point apparatus without
correction. TLC plates were visualized by exposure to ultravio-
let light. Dichloromethane and 1,2-dichloroethane were dried
by CaH2 before use, other reagents and solvents were
purchased as reagent grade and were used without further
purification. Flash column chromatography was performed
over silica gel 200–300 m and a mixture of ethyl acetate (EtOAc)
and petroleum ether (PE) was used as the eluent.
Scheme 2 Proposed reaction pathway.
However, in the absence of I2 and upon treatment of 1s with
PIDA in CH2Cl2 under reflux for 18 h, a completely different
product of 1,2-diphenylethyne 4 was obtained in 60% yield.19
A plausible reaction mechanism is proposed based on
previously reported results14b as well as this study, shown in
Scheme 2. Initially, phenylacrylic acid 1 reacts with PIDA to
form trivalent iodine B by losing two equivalents of AcOH.
Then the reaction of intermediate B with molecular iodine
forms hypoiodite C, with the concurrent release of PhI. Next,
photolysis of C leads to homolytic cleavage of the I–O bond in
C to generate the oxygen radical species D, which cyclizes to
the adjacent phenyl ring to form radical E. Furthermore,
mediated by PIDA, intermediate E is converted to cation
intermediate F via a single-electron transfer (SET) process.
Finally, the abstraction of a proton from F regenerates the
aromatic system to afford the 4-aryl coumarin 2. The
mechanism suggests that any electron-withdrawing substitu-
ents on the phenyl ring would disfavor the reaction due to the
formation of the cationic intermediate F, which is consistent
with our results concerning the nitro-substituted substrate.
Furthermore, a control experiment involving the adding of
2,2,6,6-tetramethyl-1-piperidinoxyl (TEMPO) as the additive
was carried out. It was found that the reaction could be
effectively retarded and no formation of the desired coumarin
2a was observed, which might indicate that the reaction
involves the formation of some radical species.
General procedure for the preparation of 1
According to the general procedure described in the litera-
ture,20 3,3-diarylacrylic acids were synthesized from the
corresponding benzophenones via Horner–Wadsworth–
Emmons reaction using (EtO)2P(LO)CH2CO2Et followed by
saponification.
General procedure. To a suspension of sodium hydride (1.4
g, 35 mmol, 60% in mineral oil) in THF (20 mL) was added
triethyl phosphonoacetate (5.4 g, 24.0 mmol) dropwise at 0 uC.
The mixture was stirred at room temperature for 1 h and then
a solution of benzophenone (10 mmol) in THF (10 mL) was
added. The resulting mixture was stirred at room temperature
and monitored by TLC analysis. After the completion of the
reaction, the reaction mixture was treated with saturated
aqueous NH4Cl solution (50 mL). The aqueous phase was
extracted with ethyl acetate (100 mL 6 3) and the combined
organic layer was washed with brine (100 mL 6 2) and dried
over Na2SO4. The organic solvent was removed under vacuum,
and the residue was purified by silica gel column to give the
3,3-diarylacrylic acid ester. (In the preparation of unsymmetric
products, two isomers were separated during this step,
followed by saponification respectively.)
To a solution of 3,3-diarylacrylic acid ester in a mixture
solvent EtOH/H2O (12 mL/3 mL) was added KOH (0.8 g, 14.3
mmol). The mixture was stirred at room temperature for 5 h
and then acidified with 3 M HCl. The resulting mixture was
extracted with ethyl acetate (50 mL 6 3) and the combined
organic layer was washed with brine (50 mL 6 2), H2O (50 mL)
and dried over Na2SO4. The solvent was evaporated and the
residue was purified by silica gel column chromatography to
give the desired phenylacrylic acid.
Conclusions
In conclusion, we have reported a new route to construct 4-aryl
coumarin skeletons from phenylacrylic acid through PIDA/I2-
mediated intramolecular cyclization. In contrast to all the
existing methods, this approach allows a direct, intramole-
cular C–O oxidative coupling between the sp2-carbon of the
phenyl ring and the oxygen atom of the pendant carboxylic
acid moiety. Furthermore, this method features good func-
tional-group tolerance as well as the environmentally friendly
transition-metal-free characteristic.
3,3-Diphenylacrylic acid (1a). Following the general proce-
dure, 1a was purified by silica gel chromatography (EtOAc/PE =
20/80). Yield: 60%, yellow solid, mp. 161-162 uC. 1H NMR (600
MHz, CDCl3) d 7.35–7.34 (m, 4H), 7.30 (t, J = 7.0 Hz, 2H), 7.26–
7.25 (m, 2H), 7.20–7.18 (m, 2H). 13C NMR (125 MHz, CDCl3) d
171.1, 159.0, 140.9, 138.5, 129.8, 129.3, 128.5, 128.4(6),
+
128.4(2), 127.9, 116.5. HRMS (ESI) m/z calcd for C15H13O2
[M + H+] 225.0910, found 225.0913.
3,3-Di-p-tolylacrylic acid (1b). Following the general proce-
dure, 1b was purified by silica gel chromatography (EtOAc/PE =
40/60). Yield: 61%, white solid, mp. 168–169 uC. H NMR (400
Experimental
1H and 13C NMR spectra were recorded on 400 MHz or 600
1
MHz spectrometer at 25 uC. Chemical shifts values are given in
MHz, DMSO-d6) d 7.12–7.18 (m, 6H), 7.02 (d, J = 8.0 Hz, 2H),
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6.27 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d 167.3, 154.4,
131.7, 130.0, 129.2, 128.7, 128.1, 124.3, 116.8. HRMS (ESI) m/z
calcd for C15H1279BrO2 [M + H+] 303.0015, found 303.0018.
+
139.4, 138.5, 137.6, 136.5, 129.5, 129.5, 128.9, 128.4, 118.0,
+
21.3, 21.2. HRMS (ESI) m/z calcd for C17H17O2 [M + H+]
(E)-3-(4-Bromophenyl)-3-phenylacrylic acid (1i). Following
the general procedure, 1i was purified by silica gel chromato-
graphy (EtOAc/PE = 40/60). 16% yield over 2 steps from (4-
bromophenyl)(phenyl)methanone; white solid, mp. 168–170
253.1223, found 253.1228.
3,3-Bis(4-chlorophenyl)acrylic acid (1c). Following the gen-
eral procedure, 1c was purified by silica gel chromatography
(EtOAc/PE = 30/70). Yield: 65%, white solid, mp. 174–175 uC.
1H NMR (600 MHz, DMSO-d6) d 7.44 (t, J = 8.0 Hz, 4H), 7.28 (d,
J = 8.0 Hz, 2H), 7.17 (d, J = 8.0 Hz, 2H), 6.43 (s, 1H). 13C NMR
(125 MHz, DMSO-d6) d 166.4, 151.2, 138.8, 137.3, 134.2, 132.8,
130.8, 129.6, 128.6, 128.0, 119.9. HRMS (ESI) m/z calcd for
1
uC. H NMR (400 MHz, CDCl3) d 7.49 (d, J = 8.0 Hz, 2H), 7.40–
7.30 (m, 3H), 7.25 (d, J = 8.0 Hz, 2H), 7.07 (d, J = 8.0 Hz, 2H),
6.32 (s, 1H). 13C NMR (100 MHz, CDCl3) d 171.0, 158.0, 140.3,
137.3, 131.2, 131.0, 130.0, 128.6, 128.5, 122.8, 116.7. HRMS
(ESI) m/z calcd for C15H1279BrO2 [M + H+] 303.0015, found
+
C15H1135Cl2O2 [M + H+] 293.0131, found 293.0135.
+
303.0018.
(Z)-3-(4-Cyanophenyl)-3-phenylacrylic acid (1j). Following
the general procedure, 1j was purified by silica gel chromato-
graphy (EtOAc/PE = 40/60). 26% yield over 2 steps from
4-benzoylbenzonitrile; white solid, mp. 174–176 uC. 1H NMR
(600 MHz, DMSO-d6) d 7.86 (d, J = 8.0 Hz, 2H), 7.39– 7.35 (m,
5H), 7.26 (d, J = 8.0 Hz, 2H), 6.48 (s, 1H). 13C NMR (125 MHz,
DMSO-d6) d 166.2, 152.4, 144.1, 139.2, 131.8, 129.9, 129.6,
128.7, 127.7, 119.7, 118.7, 110.5. HRMS (ESI) m/z calcd for
3,3-Bis(4-bromophenyl)acrylic acid (1d). Following the gen-
eral procedure, 1d was purified by silica gel chromatography
(EtOAc/PE = 40/60). Yield: 73%, white solid, mp. 190–192 uC.
1H NMR (400 MHz, DMSO-d6) d 12.33 (br s, 1H), 7.60–7.56 (m,
4H), 7.21 (d, J = 8.0 Hz, 2H), 7.10 (d, J = 8.0 Hz, 2H), 6.43 (s,
1H). 13C NMR (100 MHz, DMSO-d6) d 166.9, 151.8, 139.6,
138.1, 132.0, 131.6, 131.5, 130.4, 123.4, 121.9, 120.3. HRMS
(ESI) m/z calcd for C15H1179Br2O2 [M + H+] 380.9120, found
+
C16H12NO2 [M + H+] 250.0863, found 250.0863.
+
380.9121.
(E)-3-(4-Cyanophenyl)-3-phenylacrylic acid (1k). Following
the general procedure, 1k was purified by silica gel chromato-
graphy (EtOAc/PE = 40/60). 18% yield over 2 steps from
4-benzoylbenzonitrile; white solid, mp. 180–182 uC. 1H NMR
(400 MHz, DMSO-d6) d 7.83 (d, J = 8.0 Hz, 2H), 7.44 (d, J = 8.0
Hz, 2H), 7.41–7.39 (m, 3H), 7.17–7.15 (m, 2H), 6.51 (s, 1H). 13C
NMR (100 MHz, DMSO-d6) d 167.0, 151.6, 145.4, 138.4, 132.9,
129.4, 129.1, 128.7, 128.6, 122.2, 119.0, 111.9. HRMS (ESI) m/z
3,3-Bis(3-nitrophenyl)acrylic acid (1e). Following the general
procedure, 1e was purified by silica gel chromatography
(EtOAc/PE = 50/50). Yield: 80%, white solid, mp. 152–154 uC.
1H NMR (400 MHz, DMSO-d6) d 8.28 (t, J = 8.0 Hz, 2H), 8.09 (s,
1H), 8.06 (s, 1H), 7.68–7.80 (m, 4H), 6.70 (s, 1H). 13C NMR (100
MHz, DMSO–d6) d 166.5, 149.6, 148.5, 148.1, 141.5, 140.0,
136.2, 134.7, 130.8, 130.3, 124.6, 124.3, 123.7, 123.3, 122.9.
HRMS (ESI) m/z calcd for C15H11N2O6 [M + H+] 315.0612,
+
+
calcd for C16H12NO2 [M + H+] 250.0863, found 250.0863.
found 315.0612.
(Z)-3-(4-Nitrophenyl)-3-phenylacrylic acid (1l). Following the
general procedure, 1l was purified by silica gel chromatogra-
phy (EtOAc/PE = 50/50). 40% yield over 2 steps from (4-
nitrophenyl)(phenyl)methanone; white solid, mp. 181–183 uC.
1H NMR (400 MHz, DMSO-d6) d 12.39 (br s, 1H), 8.25 (d, J = 8.0
Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H),7.42–7.37 (m, 3H), 7.28 (d, J =
8.0 Hz, 2H), 6.52 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d
166.7, 152.6, 147.4, 146.7, 139.5, 130.7, 130.2, 129.2, 128.3,
(Z)-3-(4-Chlorophenyl)-3-phenylacrylic acid (1f). Following
the general procedure, 1f was purified by silica gel chromato-
graphy (EtOAc/PE = 30/70). 34% yield over 2 steps from (4-
chlorophenyl)(phenyl)methanone; white solid, mp. 167–169
uC. 1H NMR (400 MHz, DMSO-d6) d 12.28 (br s, 1H), 7.44 (d, J =
8.0 Hz, 2H), 7.40–7.35 (m, 3H), 7.27 (dd, J = 8.0, 2.0 Hz, 2 H),
7.17 (d, J = 8.0 Hz, 2H), 6.40 (s, 1H). 13C NMR (100 MHz,
DMSO-d6) d 167.0, 153.2, 140.5, 138.2, 133.1, 131.3, 129.9,
128.4, 128.3, 119.7. HRMS (ESI) m/z calcd for C15H1235ClO2+ [M
+ H+] 259.0520, found 259.0523.
123.6, 120.4. MS (ESI) m/z calcd for C15H11NO4 [M + H+]
+
270.0766, found 270.0771.
2-Cyano-3,3-diphenylacrylic acid (1m)21. To a suspension of
ethyl cyanoacetate (4.5 g, 40 mmol), benzophenone (5.4 g, 30
mmol) in heptane (13 mL) was added ammonium acetate (580
mg, 7.5 mmol) and glacial acetic acid (1.73 g, 1.65 mL). The
mixture was stirred at reflux and a 0.15 mL solution of
ammonium acetate-acetic acid was added (at a predetermined
rate) every hour for 24 h. The reaction mixture was cooled to
room temperature, treated with brine (100 mL) and then
extracted with EtOAc (100 mL 6 2). The combined organic
layer was washed with brine (100 mL 6 2) and dried over
Na2SO4. The organic solvent was removed under vacuum and
to the residue, EtOH (45 mL), H2O (15 mL), and NaOH (2.0 g,
50 mmol) were added. The mixture was stirred at room
temperature for 8 h. EtOH was removed under vacuum and the
residue was acidified with 3 M HCl. The resulting mixture was
extracted with EtOAc (100 mL 6 2) and the combined organic
layer was washed with brine (100 mL 6 3) and dried over
Na2SO4. The solvent was evaporated and the residue was
(E)-3-(4-Chlorophenyl)-3-phenylacrylic acid (1g). Following
the general procedure, 1g was purified by silica gel chromato-
graphy (EtOAc/PE = 30/70). 27% yield over 2 steps from (4-
chlorophenyl)(phenyl)methanone; white solid, mp. 150–151
1
uC. H NMR (400 MHz, DMSO-d6) d 7.43 (d, J = 8.0 Hz, 2H),
7.39–7.37 (m, 3H), 7.27 (d, J = 8.0 Hz, 2H), 7.16–7.14 (m, 2H),
6.40 (s, 1H). 13C NMR (100 MHz, DMSO-d6) d 167.1, 152.6,
139.8, 138.9, 134.4, 130.1, 129.4, 129.0, 128.5, 128.4, 120.0.
+
HRMS (ESI) m/z calcd for C15H1235ClO2 [M + H+] 259.0520,
found 259.0523.
(Z)-3-(4-Bromophenyl)-3-phenylacrylic acid (1h). Following
the general procedure, 1h was purified by silica gel chromato-
graphy (EtOAc/PE = 40/60). 24% yield over 2 steps from (4-
bromophenyl)(phenyl)methanone; white solid, mp. 165–167
uC. 1H NMR (400 MHz, CDCl3) d 7.44 (d, J = 8.0 Hz, 2H), 7.36–
7.34 (m, 3H), 7.18–7.15 (m, 2 H), 7.12 (d, J = 8.0 Hz, 2H), 6.28
(s, 1H). 13C NMR (100 MHz, CDCl3) d 171.0, 157.8, 139.8, 137.9,
4316 | RSC Adv., 2013, 3, 4311–4320
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purified by silica gel column chromatography (EtOAc/PE = 60/
40) to give 2-cyano-3,3-diphenylacrylic acid (3.2 g, 43%); white
mixture was washed with HCl 1 M (50 mL 6 2), saturated
NaHCO3 (50 mL 6 2) and water (50 mL). The organic phase
was dried over Na2SO4 and solvent was evaporated under
reduced pressure. Crude product was distilled under reduced
pressure to obtain diethyl 2-benzylidenemalonate (8.9 g, 76%).
To a solution of LiOH?H2O (0.42 g, 10 mmol) in a mixture
solvent THF/H2O (20 mL/20 mL) was added diethyl 2-benzy-
lidenmalonate (2.5 g, 10 mmol). The reaction mixture was
stirred for 5 h at room temperature. THF was evaporated under
reduced pressure. The residue was then acidified to pH = 1
with HCl (3 M), and extracted with CH2Cl2 (50 mL 6 2). The
organic phase was combined, dried over Na2SO4, evaporated
under reduced pressure. The residue was purified by silica gel
column chromatography (EtOAc/PE = 30/70) to give (Z)-2-
(ethoxycarbonyl)-3-phenylacrylic acid (1q) as white solid (1.8 g,
82%); mp. 91–92 uC. 1H NMR (400 MHz, DMSO-d6) d 13.35 (br
s, 1H, COOH), 7.67 (s, 1H, CHLC), 7.49–7.44 (m, 5H, ArH), 4.26
(q, J = 7.0 Hz, 2H,CH2), 1.20 (t, J = 7.0 Hz, 3H, CH3). 13C NMR
(100 MHz, DMSO-d6) d 166.9, 165.4, 141.0, 133.0, 131.1, 129.7,
129.4, 127.5, 61.7, 14.1.
(Z)-3-Cyano-3-phenylacrylic acid (1r)25. To a mixture of
benzonitriles (2.9 g, 25 mmol), glyoxylic acid (6.9 g, 37.5
mmol) in methanol (50.0 mL) was added potassium carbonate
(8.8 g, 64 mmol). The reaction was stirred at reflux for 8 h. The
resulting thick solid precipitate was filtered and washed with
CH2Cl2. This solid was suspended in 250 mL of cold water,
stirred for 3 h, and then filtered to provide the crude
potassium (Z)-3-cyano-3-phenylacrylate. The crude solid was
dissolved in 50 mL water and acidified by 3 M HCl. The
resulting mixture was extracted with EtOAc (100 mL 6 2) and
the combined organic phase was washed with brine (100 mL
1
solid, mp. 209–211 uC. H NMR (400 MHz, DMSO-d6) d 7.55–
7.36 (m, 5H), 7.18 (d, J = 8.0 Hz, 2H). 13C NMR (100 MHz,
DMSO-d6) d 167.7, 163.7, 139.2, 138.9, 131.4, 130.5, 130.0,
129.5, 129.0, 128.6, 117.7, 105.9.
2,3,3-Triphenylacrylic acid (1n)22. 1) To a suspension of NaH
(2.2 g, 55 mmol, 60% in mineral oil) in THF (50 mL) was added
phenylacetonitrile (5.8 mL, 50 mmol). The reaction mixture
was stirred at 40 uC for 2 h and then cooled to room
temperature whereupon a solution of benzophenone (1.8 g, 10
mmol) in THF (30 mL) was added dropwise via a dropping
funnel. The resultant solution was heated to reflux for 6 h. The
reaction mixture was cooled to room temperature and the
solvent was removed under reduced pressure. The residue was
dissolved
in
a
2.5 : 2.5 : 1
solvent
mixture
of
THF : MeOH : HCl (2 M, 60 mL) and stirred at room
temperature for 3 h. The solvents were concentrated under
reduced pressure and the aqueous layer was extracted with
EtOAc (100 mL 6 2). The combined organic phase was washed
with saturated NaHCO3 (100 mL), brine (100 mL 6 2) and
dried over Na2SO4. After the removal of the solvent via
evaporation, the residue was purified by recrystallization with
EtOAc/PE to give 2,3,3-triphenylacrylonitrile (1.7 g, 68%).
2) To a stirred solution of 2,3,3-triphenylacrylonitrile (1.1 g,
4 mmol), KOH (1.1 g, 20 mmol) in H2O (0.27 mL, 5 mmol) and
ethylene glycol (20 mL) were heated at 185 uC. Every hour of
the reaction time period H2O (0.3 mL) was added cautiously.
The mixture was heated for 48 h and cooled to room
temperature. The mixture was acidified with 3 M HCl to pH
= 5–6 and extracted with EtOAc (50 mL 6 2) and the combined
organic phase was washed with brine (50 mL 6 3). The
organic phase was dried over Na2SO4 and evaporated under
reduced pressure. The residue was purified by silica gel
column chromatography (EtOAc/PE = 30/70) to give 2,3,3-
triphenylacrylic acid (0.85 g, 71%); white solid, mp. 211–212
6
2). The organic phase was dried over Na2SO4 and
evaporated under reduced pressure. The residue was purified
by silica gel column chromatography (EtOAc/PE = 30/70) to
give (Z)-3-cyano-3-phenylacrylic acid (3.8 g, 69%); white solid,
1
mp. 140–142 uC. H NMR (400 MHz, DMSO-d6) d 13.54 (br s,
1
uC. H NMR (400 MHz, CDCl3) d 7.34–7.27 (m, 5H), 7.20–7.09
1H, COOH), 7.81–7.79 (m, 2H), 7.54–7.52 (m, 3H), 7.27 (s, 1H).
13C NMR (100 MHz, DMSO-d6) d 165.0, 132.8, 132.1, 131.8,
129.8, 127.4, 124.2, 115.8.
(m, 8H), 6.96 (d, J = 7.0 Hz, 2H). 13C NMR (100 MHz, CDCl3) d
174.9, 148.4, 142.0, 140.5, 137.4, 132.2, 130.9, 130.1, 129.1,
128.4, 128.2, 127.8, 127.8, 127.6.
3,3-Bis(4-methoxyphenyl)acrylic acid (1s). Following the
general procedure, 1s was purified by silica gel chromatogra-
phy (EtOAc/PE = 30/70). Yield: 77%, white solid, mp. 142–143
uC. 1H NMR (400 MHz, CDCl3) d7.21 (d, J = 8.0 Hz, 2H), 7.14 (d,
J = 8.0 Hz, 2H), 6.82– 6.88 (m, 4H), 6.17 (s, 1H), 3.83 (s, 3H),
3.80 (s, 3H). 13C NMR (100 MHz, CDCl3) d 171.6, 161.0, 160.0,
158.8, 133.8, 131.1, 130.7, 130.3, 113.9, 113.8, 113.3, 55.4, 55.2.
MS (ESI) m/z calcd for C17H17O4+ [M + H+] 285.1121, found
285.1124.
(Z)-3-Phenylbut-2-enoic acid (1o)23. Following the general
procedure, 1o was purified by silica gel chromatography
(EtOAc/PE = 30/70). Yield: 14%, white solid, mp. 131–133 uC.
1H NMR (400 MHz, DMSO-d6) d 11.90 (br s, 1H), 7.21–7.33 (m,
5H), 5.89 (s, 1H), 2.12 (s, 3H). 13C NMR (100 MHz, DMSO-d6) d
167.2, 153.5, 141.1, 128.2, 128.0, 127.5, 118.9, 27.0.
(E)-3-Phenylbut-2-enoic acid (1p). Following the general
procedure, 1p was purified by silica gel chromatography
(EtOAc/PE = 30/70). Yield: 42%, white solid, mp. 97–99 uC.
1H NMR (400 MHz, CDCl3) d 7.51–7.49 (m, 2H), 7.40–7.38 (m,
3H), 6.18 (s, 1H, CLCH), 2.61 (s, 3H, CH3). Physical and
spectral data were consistent with those reported in the
literature.23b
(Z)-2-(Ethoxycarbonyl)-3-phenylacrylic acid (1q)24. To a mix-
ture of diethyl malonate (6.4 mL), benzaldehyde (5.0 mL) in
anhydrous toluene (15.0 mL) was added piperidine (0.5 mL). A
4 Å molecular sieve (0.2 g) was added and the reaction was
stirred at reflux for 15 h. EtOAc (50 mL) was added and the
General procedure for the preparation of coumarins 2
To a solution of phenylacrylic acid 1 (0.2 mmol) in dry CH2Cl2
(4 mL) in a 25 mL round-bottom flask was added PIDA (97 mg,
0.3 mmol). The mixture was stirred at rt for 5 min and then I2
(10.2 mg, 0.04 mmol) was added. The reaction mixture was
stirred at rt under irradiation with a tungsten lamp (200 W)
and monitored by TLC analysis. After the completion of the
reaction, the reaction mixture was concentrated in vacuo to
remove the solvent. The residue was purified by silica gel
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(ESI) m/z calcd for C15H1035ClO2 [M + H+] 257.0364, found
+
chromatography using a mixture of petroleum ether (PE) and
ethyl acetate (EtOAc) as eluent, to give the desired product 2.
257.2.
4-Phenyl-2H-chromen-2-one (2a)
4-(4-Chlorophenyl)-2H-chromen-2-one (2g)
Following the general procedure, 2a was purified by silica gel
chromatography (EA/PE = 5/95). Yield: 92%, white solid, mp.
90–91 uC. 1H NMR (400 MHz, CDCl3) d 7.57–7.40 (m, 8H), 7.23
(t, J = 8.0 Hz, 1H), 6.39 (s, 1H). 13C NMR (100 MHz, CDCl3) d
160.7, 155.7, 154.2, 135.2, 131.9, 129.7, 128.9, 128.4, 127.0,
124.2, 119.0, 117.3, 115.2. HRMS (ESI) m/z calcd for
Following the general procedure, 2g was purified by silica gel
chromatography (EA/PE = 10/90). Yield: 78%, white solid, mp.
187–188 uC. 1H NMR (400 MHz, CDCl3) d 7.57 (t, J = 8.0 H, 1H),
7.52 (d, J = 8.0 H, 2H), 7.46–7.40 (m, 4H), 7.25 (t, J = 8.0 H, 1H),
6.37 (s, 1H). 13C NMR (100 MHz, CDCl3) d 160.5, 154.4, 154.2,
136.0, 133.6, 132.2, 129.8, 129.2, 126.7, 124.3, 118.7, 117.5,
115.4. The spectral data are identical to those reported in the
literature.10
C15H10NaO2 [M + Na+] 245.0573, found 245.0577.
+
7-Methyl-4-(p-tolyl)-2H-chromen-2-one (2b)
7-Bromo-4-phenyl-2H-chromen-2-one (2h)
Following the general procedure, 2b was purified by silica gel
chromatography (EA/PE = 10/90). Yield: 81%, white solid, mp.
153–154 uC. H NMR (400 MHz, CDCl3) d 7.40 (d, J = 8.0 Hz,
Following the general procedure, 2h was purified by silica gel
chromatography (EA/PE = 10/90). Yield: 67%, white solid, mp.
102–104 uC. 1H NMR (400 MHz, CDCl3) d 7.57 (s, 1H, 7.54–7.53
(m, 3H), 7.44–7.42 (m, 2H), 7.35 (m, 2H), 6.38 (s, 1H). 13C NMR
(100 MHz, CDCl3) d 159.9, 155.1, 154.4, 134.8, 130.0, 129.0,
128.3, 128.0, 127.6, 125.9, 120.5, 118.0, 115.3. HRMS (ESI) m/z
calcd for C15H979BrNaO2+ [M + Na+] 322.9678, found 322.9680.
1
2H), 7.36 (m, 4H), 7.20 (s, 1H), 7.03 (d, J = 8.0 Hz, 2H), 6.29 (s,
1H), 2.45 (s, 6H). 13C NMR (100 MHz, CDCl3) d 161.2, 155.7,
154.3, 143.1, 139.8, 132.5, 129.5, 128.4, 126.7, 125.3, 117.4,
116.7, 113.8, 21.6, 21.4. HRMS (ESI) m/z calcd for C17H15O2+ [M
+ H+] 251.1067, found 251.1068.
7-Chloro-4-(4-chlorophenyl)-2H-chromen-2-one (2c)
4-(4-Bromophenyl)-2H-chromen-2-one (2i)
Following the general procedure, 2c was purified by silica gel
Following the general procedure, 2i was purified by silica gel
chromatography (EA/PE = 5/95). Yield: 82%, white solid, mp.
162–163 uC. H NMR (400 MHz, CDCl3) d 7.52 (d, J = 8.0 Hz,
chromatography (EA/PE = 10/90). Yield: 75%, white solid, mp.
202–203 uC. H NMR (400 MHz, CDCl3) d 7.68 (d, J = 8.0 Hz,
1
1
2H), 7.43 (d, J = 2.0 Hz, 1H) 7.36–7.39 (m, 3H), 7.22 (dd, J = 2.0
Hz, J = 8.0 Hz, 1H), 6.35 (s, 1H). 13C NMR (100 MHz, CDCl3) d
159.7, 154.5, 153.8, 138.2, 136.3, 133.2, 129.7, 129.4, 127.6,
124.9, 117.7, 117.4, 115.2. HRMS (ESI) m/z calcd for
2H), 7.57 (t, J = 8.0 Hz, 1H), 7.43 (t, J = 8.0 Hz, 2H), 7.34 (d, J =
8.0 Hz, 2H), 7.25 (t, J = 8.0 Hz, 1H), 6.37 (s, 1H). 13C NMR (100
MHz, CDCl3) d 160.4, 154.4, 154.2, 134.0, 132.2, 132.2, 130.0,
126.7, 124.3, 124.2, 118.6, 117.5, 115.4. HRMS (ESI) m/z calcd
C15H935Cl2O2 [M + H+] 290.9974, found 290.9979.
for C15H979BrNaO2 [M + Na+] 322.9678, found 322.9681.
+
+
7-Bromo-4-(4-bromophenyl)-2H-chromen-2-one (2d)
2-Oxo-4-phenyl-2H-chromene-7-carbonitrile (2j)
Following the general procedure, 2d was purified by silica gel
Following the general procedure, 2j was purified by silica gel
chromatography (EA/PE = 5/95). Yield: 68%, white solid, mp.
166–168 uC. H NMR (400 MHz, CDCl3) d 7.68 (d, J = 8.0 Hz,
chromatography (EA/PE = 10/90). Yield: 61%, white solid, mp.
134–135 uC. H NMR (600 MHz, CDCl3) d 7.69 (d, J = 1.0 Hz,
1
1
2H), 7.59 (d, J = 2.0 Hz, 1H), 7.37 (dd, J = 8.0, 2.0 Hz, 1H), 7.32–
7.28 (m, 3H), 6.37 (s, 1H). 13C NMR (100 MHz, CDCl3) d 159.5,
154.4, 153.9, 133.6, 132.3, 129.9, 127.7, 127.6, 126.2, 124.5,
120.7, 117.7, 115.4. HRMS (ESI) m/z calcd for C15H979Br2O2+ [M
+ H+] 378.8964, found 378.8967.
1H), 7.61 (d, J = 8.0 Hz, 1H), 7.57–7.56 (m, 3H), 7.49 (dd, J = 1.0
Hz, J = 8.0 Hz, 1H), 7.44–7.22 (m, 2H), 6.51 (s, 1H). 13C NMR
(125 MHz, CDCl3) d 159.0, 154.3, 153.7, 134.0, 130.3, 129.2,
128.3, 128.0, 127.2, 122.7, 121.0, 117.8, 117.3, 115.0. HRMS
(ESI) m/z calcd for C16H10NO2 [M + H+] 248.0706, found
+
248.0707.
6-Nitro-4-(3-nitrophenyl)-2H-chromen-2-one (2e)
4-(2-Oxo-2H-chromen-4-yl)benzonitrile (2k)
Following the general procedure, 2e was purified by silica gel
chromatography (EA/PE = 10/90). Yield: 46%, white solid, mp.
176–178 uC. 1H NMR (400 MHz, CDCl3) d 8.50–8.46 (m, 2H),
8.37 (s, 1H), 8.25 (d, J = 2.0 Hz, 1H), 7.87– 7.81 (m, 2H), 7.59 (d,
J = 9.0 Hz, 1H), 6.58 (s, 1H). 13C NMR (100 MHz, CDCl3) d
158.1, 157.7, 152.2, 148.8, 144.2, 135.3, 134.0, 130.8, 127.3,
125.3, 123.4, 122.2, 118.9, 118.6, 118.1. HRMS (ESI) m/z calcd
Following the general procedure, 2k was purified by silica gel
chromatography (EA/PE = 15/85). Yield: 65%, white solid, mp.
1
243–245 uC. H NMR (400 MHz, CDCl3) d 7.85 (d, J = 8.0 Hz,
2H), 7.62–7.58 (m, 3H), 7.44 (d, J = 8.0 Hz, 1H), 7.34 (d, J = 8.0
Hz, 1H), 7.28–7.24 (m, 1H), 6.39 (s, 1H). 13C NMR (125 MHz,
CDCl3) d 160.0, 154.2, 153.6, 139.7, 132.7, 132.5, 129.3, 126.3,
124.5, 118.2, 118.0, 117.7, 116.0, 113.8. HRMS (ESI) m/z calcd
for C15H9N2O6 [M + H+] 313.0455, found 313.0455.
+
+
for C16H9NNaO2 [M + Na+] 270.0525, found 270.0530.
7-Chloro-4-phenyl-2H-chromen-2-one (2f)26
7-Nitro-4-phenyl-2H-chromen-2-one (2l)
Following the general procedure, 2f was purified by silica gel
chromatography (EA/PE = 10/90). Yield: 84%, yellow solid, mp.
100–102 uC. 1H NMR (400 MHz, CDCl3) d 7.55–7.53 (m, 3H),
7.44–7.42 (m, 4H), 7.20 (dd, J = 8.0, 2.0 Hz, 2 H), 6.37 (s, 1H).
13C NMR (100 MHz, CDCl3) d 160.1, 155.1, 154.5, 137.9, 134.8,
130.0, 129.0, 128.4, 128.0, 124.7, 117.7, 117.5, 115.0. HRMS
Following the general procedure, 2l was purified by silica gel
chromatography (EA/PE = 10/90). Yield: 59%, white solid, mp.
1
135–137 uC. H NMR (600 MHz, CDCl3) d 8.23 (d, J = 2.0 Hz,
1H), 8.06 (dd, J = 9.0, 2.0 Hz, 1H), 7.68 (d, J = 9.0 Hz, 1H), 7.57–
7.59 (m, 3H), 7.46–7.44 (m, 2H), 6.54 (s, 1H). 13C NMR (125
4318 | RSC Adv., 2013, 3, 4311–4320
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+
MHz, CDCl3) d 159.1, 154.2, 153.9, 149.3, 134.1, 130.4, 129.3,
128.3, 128.2, 124.0, 118.6, 118.0, 112.9. HRMS (ESI) m/z calcd
88.0, 55.3. HRMS (ESI) m/z calcd for C16H15O2 [M + H+]
239.1067, found 239.1072.
+
for C15H10NO4 [M + H+] 268.0604, found 268.0606.
2-Oxo-4-phenyl-2H-chromene-3-carbonitrile (2m)
Acknowledgements
Following the general procedure, 2m was purified by silica gel
chromatography (EA/PE = 20/80). Yield: 76%, yellow solid, mp.
217–218 uC. 1H NMR (400 MHz, CDCl3) d 7.73–7.69 (m,1H),
7.63–7.61 (m, 3H), 7.50–7.46 (m, 3H), 7.40 (d, J = 8.0 Hz, 1H),
7.32 (t, J = 8.0 Hz, 1H) 13C NMR (100 MHz, CDCl3) d 164.2,
157.0, 154.0, 135.3, 131.7, 131.2, 129.2, 129.0, 128.5, 125.4,
118.1, 117.7, 113.6, 101.7. HRMS (ESI) m/z calcd for
Y.D. acknowledge the National Natural Science Foundation of
China (#21072148) for financial support.
Notes and references
+
C16H9NNaO2 [M + Na+] 270.0531, found 270.0536.
1 (a) R. D. H. Murray, Nat. Prod. Rep., 1995, 12, 477; (b)
´
´
A. Estevez-Braun and A. G. Gonzalez, Nat. Prod. Rep., 1997,
14, 465; (c) V. M. Malikov and A. I. Saidkhodzhaev, Khim.
Prir. Soedin., 1998, 34, 250; (d) M. M. Garazd, Y. L. Garazd
and V. P. Khilya, Chem. Nat. Compd., 2003, 39, 54.
2 M. M. Garazd, Y. L. Garazd and V. P. Khilya, Khim. Prir.
Soedin., 2003, 39, 47.
3,4-Diphenyl-2H-chromen-2-one (2n)
Following the general procedure, 2n was purified by silica gel
chromatography (EA/PE = 10/90). Yield: 43%, white solid, mp.
228–229 uC. 1H NMR (400 MHz, CDCl3) d 7.56–7.52 (m, 1H),
7.43 (d, J = 8.0 Hz, 1H), 7.30–7.31 (m, 3H), 7.24–7.12 (m, 9H).
13C NMR (100 MHz, CDCl3) d 161.3, 153.3, 151.6, 134.5, 133.9,
131.5, 130.5, 129.4, 128.4, 128.3, 127.8, 127.7, 127.6, 127.0,
3 (a) S. F. Wu, S. L. Chen, C. C. Wu, C. F. Wu, Y. Wu, T.
L. Hwang, E. Ohkoshi and K. Lee, Bioorg. Med. Chem. Lett.,
2011, 21, 5630; (b) L. M. Bedoya, M. Beltran, R. Sancho, D.
´
+
124.1, 120.5, 116.8. HRMS (ESI) m/z calcd for C21H15O2 [M +
´
´
A. Olmedo, S. Sanchez-Palomino, E. Olmo, J. L. Lpez-Perez,
H+] 299.1067, found 299.1069.
˜
´
E. Munoz, A. S. Feliciano and J. Alcamı, Bioorg. Med. Chem.
Lett., 2005, 15, 4447; (c) M. C. Yimdjo, A. G. Azebade, A.
E. Nkengfack, A. M. Meyer, B. Bodo and Z. T. Fomum,
Phytochemistry, 2004, 65, 2789; (d) R. Argotte-Ramos,
4-Methyl-2H-chromen-2-one (2o)
Following the general procedure, 2o was purified by silica gel
chromatography (EA/PE = 10/90). Yield: 85%, white solid, mp.
82–83 uC. 1H NMR (600 MHz, CDCl3) d 7.61 (d, J = 8.0 Hz, 1H),
7.53 (t, J = 8.0 Hz, 1H), 7.34–7.29 (m, 2H), 6.30 (s, 1H), 2.45 (s,
3H). 13C NMR (125 MHz, CDCl3) d 160.8, 153.6, 152.3, 131.8,
124.6, 124.2, 120.0, 117.1, 115.1, 18.6. HRMS (ESI) m/z calcd for
´
´
´
G. Ramırez-Avila, M. C. Rodrıguez-Gutierrez, M. Ovilla-
˜
´
´
Munoz, H. Lanz-Mendoza, M. H. Rodrıguez, M. Gonzalez-
Cortazar and L. Alvarez, J. Nat. Prod., 2006, 69, 1442.
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Compd., 2005, 41, 245; (b) M. M. Garazd, Y. L. Garazd and
V. P. Khilya, Khim. Prir. Soedin., 2005, 41, 199.
+
C21H15O2 [M + H+] 161.0597, found 161.0582.
5 For selected examples, see: (a) J. Crecente-Campo, M.
P. Vazquez-Tato and J. A. Seijas, Eur. J. Org. Chem., 2010,
4130; (b) I. Hwang, S. Lee, J. Hwang and K. Lee, Molecules,
2011, 16, 6313.
Ethyl 2-oxo-2H-chromene-3-carboxylate (2q)
Following the general procedure, 2q was purified by silica gel
chromatography (EA/PE = 10/90). Yield: 41%, white solid, mp.
1
93–95 uC. H NMR (400 MHz, CDCl3) d 8.53 (s, 1H), 7.67–7.61
6 For selected examples, see: (a) C. Jia, D. Piao, J. Oyamada,
W. Lu, T. Kitamura and Y. Fujiwara, Science, 2000, 287,
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Chem., 2000, 65, 7516; (c) T. Kitamura, K. Yamamoto,
M. Kotani, J. Oyamada, C. Jia and Y. Fujiwara, Bull. Chem.
Soc. Jpn., 2003, 76, 1889; (d) S. J. Pastine, S. W. Youn and
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62, 6918; (h) Z. Shi and C. He, J. Org. Chem., 2004, 69, 3669;
(i) K. Li, Y. Zeng, B. Neuenswander and J. A. Tunge, J. Org.
Chem., 2005, 70, 6515; (j) J. Sun, W. X. Ding, K. Y. Zhang
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(m, 2H), 7.38–7.32 (m, 2H), 4.42 (q, J = 7.0 Hz, 2H), 1.42 (t, J =
7.0 Hz, 3H). 13C NMR (100 MHz, CDCl3) d 163.0, 156.7, 155.1,
148.6, 134.3, 129.5, 124.9, 118.3, 117.9, 116.8, 62.0, 14.2. HRMS
(ESI) m/z calcd for C12H11O4 [M + H+] 219.0652, found
+
219.0653.
4,4’-(2-Iodoethene-1,1-diyl)bis(methoxybenzene) (3)
Following the general procedure, 3 was purified by silica gel
chromatography (EA/PE = 3/97). Yield: 82%, yellow oil. 1H
NMR (400 MHz, CDCl3) d 7.20 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 8.0
Hz, 2H), 6.92 (d, J = 8.0 Hz, 2H), 6.79 (d, J = 8.0 Hz, 2H), 6.71 (s,
1H), 3.84 (s, 3H), 3.79 (s, 3H). 13C NMR (100 MHz, CDCl3) d
159.6, 159.2, 151.7, 134.4, 134.3, 130.9, 130.0, 113.7, 113.6,
76.0, 55.3, 55.2. HRMS(ESI) m/z calcd for C16H15O2 [M + H+]
239.1067, found 239.1069.
+
7 (a) E. R. Krajniak, E. Ritchie and W. C. Taylor, Aust. J.
Chem., 1973, 26, 899; (b) A. K. Das Gupta and M. S. Paul, J.
Indian Chem. Soc., 1970, 47, 95.
1,2-Bis(4-methoxyphenyl)ethyne (4)
8 For selected examples, see: (a) P. G. Ciattini, E. Morera and
G. Ortar, Synth. Commun., 1995, 25, 2883; (b) G. M. Boland,
D. M. X. Donnelly, J. Finet and M. D. Rea, J. Chem. Soc.,
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Following the general procedure, without the addition of I2, 4
was purified by silica gel chromatography (EA/PE = 5/95).
1
Yield: 60%, white solid, mp. 140–142 uC. H NMR (400 MHz,
CDCl3) d 7.45 (d, J = 8.0 Hz, 4H), 6.86 (d, J = 8.0 Hz, 4H), 3.82 (s,
6H). 13C NMR (100 MHz, CDCl3) d 159.4, 132.9, 115.7, 114.0,
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¯
26 Compound 2f, crystallized in the triclinic space group P1
with cell dimensions: a = 9.6658(12) Å, b = 10.3292(14) Å, c
= 18.5201(18) Å, a = 85.61(12)u, b = 86.14(14)u, c = 81.72(10)u,
V = 1821.5(4) Å3, Dc = 1.404 g cm23, Z = 6. CCDC 911557.
4320 | RSC Adv., 2013, 3, 4311–4320
This journal is ß The Royal Society of Chemistry 2013