Domino reactions of alkenyl p-benzoquinones: Access to aryl sulfide derivatives of coumarins

Article abstract of DOI:10.1016/j.tet.2017.03.030

An efficient domino approach has been developed for the synthesis of coumarin aryl sulfides utilizing alkenyl arenes derived electrophilic alkenyl p-benzoquinones through Michael addition of thiols followed by cyclization. The reaction proceeds regioselec

Full text of DOI:10.1016/j.tet.2017.03.030

Accepted Manuscript
Domino reactions of alkenyl p-benzoquinones: Access to aryl sulfide derivatives of
coumarins
Shweta Bisht, Rama Krishna Peddinti
PII:
S0040-4020(17)30268-5
10.1016/j.tet.2017.03.030
TET 28536
DOI:
Reference:
To appear in: Tetrahedron
Received Date: 1 February 2017
Revised Date: 3 March 2017
Accepted Date: 10 March 2017
Please cite this article as: Bisht S, Peddinti RK, Domino reactions of alkenyl p-benzoquinones: Access to
aryl sulfide derivatives of coumarins, Tetrahedron (2017), doi: 10.1016/j.tet.2017.03.030.
This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to
our customers we are providing this early version of the manuscript. The manuscript will undergo
copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please
note that during the production process errors may be discovered which could affect the content, and all
legal disclaimers that apply to the journal pertain.

ACCEPTED MANUSCRIPT
Graphical Abstract
To create your abstract, type over the instructions in the template box below.
Fonts or abstract dimensions should not be changed or altered.
Domino Reactions of Alkenyl p-
Benzoquinones: Access to Aryl Sulfide
Derivatives of Coumarins
Leave this area blank for abstract info.
Shweta Bisht, and Rama Krishna Peddinti*
Department of Chemistry, Indian Institute of Technology, Roorkee-247667, Uttarakhand, India

1
ACCEPTED MANUSCRIPT
Tetrahedron
journal homepage: www.elsevier.com
Domino Reactions of Alkenyl p-Benzoquinones: Access to Aryl Sulfide Derivatives
of Coumarins
Shweta Bisht, and Rama Krishna Peddinti*
aDepartment of Chemistry, Indian Institute of Technology Roorkee, Roorkee, Uttarakhand-247667, India
ARTICLE INFO
ABSTRACT
Article history:
Received
Received in revised form
Accepted
An efficient domino approach has been developed for the synthesis of coumarin aryl sulfides
utilizing alkenyl arenes derived electrophilic alkenyl p-benzoquinones through Michael addition
of thiols followed by cyclization. The reaction proceeds regioselectively under mild conditions
within short reaction time to afford the title products in good to excellent yields. This catalyst-
free reaction has good substrate scope.
Available online
Keywords:
Domino approach
Coumarin
2009 Elsevier Ltd. All rights reserved
.
Biaryl sulfides
Cyclization
Complex Molecule
1. Introduction
OMe
NEt2
In the enormously progressing field of synthetic chemistry, the
edifice of carbon–heteroatom bond formation is an important
strategy for the construction of complex organic molecules.1
Domino approach is one of the major tool to construct
biologically important complex molecules from simple substrates
in one-pot fashion which is ecologically and economically
benign.2 p-Quinone3,4 is one of the potent starting materials for
the synthesis of compounds having biological profiles.5,6 p-
Quinones react with thiols to generate hydroquinones bearing
arylthio moiety.7 In recent years, p-quinones have been
derivatized in more useful forms like nitrovinyl p-quinones8 and
alkenyl p-benzoquinones.9 The alkenyl p-benzoquinones are
fascinating precursors for the cascade protocol due to their
inherent multiple functionalities. The alkenyl p-benzoquinones
have potential to react with alkyl and aryl thiols to generate alkyl
or aryl sulfide derivatives of coumarins which seem to be
promising bioactive compounds since coumarins10 and biaryl
sulfides11 have enriched literature of bioactivity such as anti-
inflammatory, anti-malarial, anti-cancer and anti-HIV activities
(Figure 1).12–14 In addition, coumarin derivatives derived from
alkenyl p-benzoquinone have also found application in
fluorescence probe.15 However, the reports on the synthesis of
coumarin-coupled aryl sulfides are scarce.16 Keeping the above in
mind, we hypothesized that alkenyl p-benzoquinones, having
multiple sites for nucleophilic attack, can undergo Michael
addition with thiols followed by cyclization in domino fashion,
resulting in the formation of novel aryl sulfide derivatives of
coumarin of types I, II and III (Scheme 1). These compounds are
interesting due to the presence of both coumarin and aryl sulfide
moiety. In continuation of our work on harnessing the reactivity
OMe
O
S
HN
S
OMe
CO2Me
N
H
antiinflammatory agent
MCF-6 growth inhibitor
CF3
F3C
O
N
R
O
S
O
O
N
O2N
HO
S
O
F
coumarin–thiazoline
hybrids as potent
anti-tubercular agents
5-lipoxygenase inhibitor
F
Figure 1. Some of the diaryl sulfide containing biologically
active compounds.
of benzoquinone derivatives17 and synthesis of diaryl sulphides,18
herein, we report a rapid, novel and efficient method for the
Scheme 1. Working hypothesis.
synthesis of aryl sulfide derivatives of coumarin through
sequential construction of C–S and C–O bonds in a domino
sequence. The current strategy involves one-pot domino Michael

2
addition cyclization protocol to produce coumarin-based aryl mixture of 5b and 2a′ in a combined yield of 18% (Table 1, entry
sulfides.
ACCEPTED MANUSCRIPT
1) where the regioisomers 4b and 5b resulted from the addition of
3b on alkenyl p-benzoquinone 2a at position 3 and position 6,
respectively.
2. Results and Discussion
Accordingly, the alkenyl p-benzoquinones 2a-d, were
synthesized19 by the oxidative demethylation of the
corresponding alkenylarenes 1a-d (Scheme 2). Since the oxidized
products 2a-d are pure, as checked by 1H NMR, they are used as
such after work-up without purification.
Encouraged by this result, we sought to optimize the reaction
conditions in various solvents such as THF, ethyl lactate, toluene,
CH2Cl2, CHCl3, EtOH, MeOH, H2O and found that the nature of
solvent has great impact on the reaction outcome. In polar/non-
polar aprotic solvents, 4b was obtained in comparatively lower
yield along with varying amounts of 5b and 2a′ (entries 2–6). On
switching towards the polar protic solvents, as in case of water, 4b
was obtained selectively in 41% yield along with 2a′ (22%) (entry
7). In the reaction performed in EtOH and MeOH, both
regioisomers 4b and 5b were formed in good yield (entries 8 and
9). Further, the reaction in a 1:1 mixture of MeOH and H2O proved
to be less reactive (entry 10). Though the reaction proceeds in all
solvents, it worked more efficiently in MeOH where 4b was
obtained as major isomer and 5b in minor quantity.
a: X = H, R = Me
b: X = H, R = Et
c: X = Br, R = Me
Used after work-up
without further purification
After identifying the suitable solvent, we performed the reaction
at lower temperature and found that the reaction temperature had a
great influence on the reaction outcome. The decrease in
temperature led to an increase in the yield of the products (entries
11–13). When the amount of 2a was increased from 1 equiv to 1.3
equiv, the reaction worked efficiently to afford a separable mixture
of two regioisomers 4b and 5b in 73 and 18% yield, respectively
(Table 1, entry 14). Thus, the screening of various parameters
identified the above condition as the optimal for this
transformation.
Used after work-up
without further purification
Scheme 2. Oxidation of 1,4-dimethoxy-alkenyl arenes to p-
quinones 2a-d.
Table 1. Optimization of reaction conditions.a
In view of the success of the above reaction, the scope of the
reaction of 2a was exemplified with various substituted
thiophenols under the optimized reaction conditions. The nature of
substituent on aryl ring of thiophenols 3a–f affected the reaction
yield of diaryl sulfides 4a–f and 5a–f slightly. Electron–donating
groups on aryl ring of thiophenol showed more reactivity than
those with electron-withdrawing groups (Table 2). For example, 4-
methoxythiophenol (3c) produced the products 4c and 5c in 75 and
15% yield, respectively. Use of 2-naphthalenethiol (3d), delivered
4d and 5d in 75 and 18% yield, respectively. Notably, the reactions
of 3e and 3f bearing electron-withdrawing halo groups furnished
the sulfides 4e and 5e in 72 and 13%, and 4f and 5f in 71 and 13%
yield, respectively. The slight reduction in the yield may be
attributed to the moderate electron-withdrawing nature of the halo
substituents. The structures of the both regioisomers were
temp/
time (min)
yield (%)b
Entry
solvent
4b
55
5b/2a′
1
2
3
4
5
6
7
8
9
10d
11
12
13
14e
CH3CN
THF
Ethyl lactate
Toluene
CH2Cl2
CHCl3
H2O
Ethanol
MeOH
rt/5
rt/5
rt/5
rt/5
rt/5
rt/5
rt/10
rt/5
rt/1
18c
35c
22c
20c
23c
22c
47
50
57
60
55
41
55
63
42
65
68
70
73
1
unambiguously confirmed by H NMR analysis by the inspection
of coupling constants. In case of 4c, ortho coupling (J = 9.5 Hz) is
observed between H-7 and H-8 protons which indicates that
thiophenol is attached at 3rd position of alkenyl p-benzoquinone 2a.
In case of 5c, H-5 and H-7 protons showed meta coupling (J = 2.5
Hz) confirming the addition of thiophenol at 6th position of 2a.
Moreover, the structures of 4e and 5e were confirmed by their
single crystal X-ray analysis (Figure 2).20
2a′ (22)
5b (19)
5b (21)
2a′ (27)
5b (18)
5b (17)
5b (18)
5b (18)
MeOH+H2O
MeOH
rt/10
0 oC /1
–20 oC /1
–40 oC /1
–40 oC /1
MeOH
MeOH
MeOH
Inspired by the above results, we further extended the scope of
the reaction of alkenyl p-benzoquinone 2b bearing ethyl ester
with various thiophenols and here again the reaction proceeded
smoothly under the optimized conditions. Moreover, electron-
donating and withdrawing groups on the aryl ring of thiophenol
were well tolerated, leading to the desired major products 6a–f
and minor 7a-f in good yields (Table 2).
a All reactions were performed with 2a (0.5 mmol), 3b (0.5 mmol) in 1 mL of
b
solvent. Yield of isolated products after column chromatography, unless
c
1
otherwise noted. Combined yield of 5b and 2a′ as determined by H NMR
d
e
analysis. MeOH and H2O (1:1). 2a (1.0 mmol) and 3b (0.6 mmol) were
used.
As a prelude to our objective, we performed the reaction of
alkenyl p-benzoquinone 2a and 4-methylthiophenol (3b) in
acetonitrile at room temperature. To our delight, aryl sulfide
derivative of coumarin 4b was obtained in 55% yield along with a

3
Table 2. Scope of thiols and alkenyl p-benzoquinones.a,b
ACCEPTED MANUSCRIPT
aThe reaction was carried out using 2a/2b (1.0 mmol) and 3a–f (0.6 mmol) in MeOH (1 mL) at –40 oC. bIsolated yield after column chromatography.
under the optimized conditions and afforded the anticipated
products 8a–f in good yields of 65–78% (Table 3). In addition,
2c′ was obtained as minor product in each case.
O
CO2Me
O
Br
The feasibility and scope of the above reaction was also
evaluated with aliphatic thiols 3g and 3h. To our delight, it was
found that when aliphatic thiols reacted with alkenyl p-
S
4e
OH
benzoquinones 2a-c,
a single regioisomer was produced
exclusively in each case in very good yield along with 2a′-c′ in 2
min (Table 4). This observation reflected the fact that the
reactions of arylthiols are relatively faster than those of
alkylthiols as recorded in the literature.21
Figure 2. Single crystal X-ray structure of compound 4e and 5e.
To further extend the scope of the current domino protocol,
bromo derivative 2c of alkenyl p-benzoquinone was treated with
various thiophenols under the same conditions. Astonishingly,
regioselective addition of the nucleophile at position 3 of 2c was
observed resulting in the formation of the diaryl sulfides 8. This
may be attributed due to the stereoelectronic effect of bromo
group situated at 5th position of 2c. Thus a series of thiophenols
bearing methyl, methoxy, chloro, bromo substituted at para
position of phenyl ring and 2-naphthylthiol were well tolerated

4
Table 3 Scope of domino reaction of alkenyl p-benzoquinones
afford the products 9g and 9h regioselectively in 70 and 68%
yield, respectively (Table 5).
ACCEPTED MANUSCRIPT
with thiols.a,b
Table 5. Thiolation of alkenyl p-benzoquinone 2da,b
O
O
CO2Me
CO2Me
O
O
O
MeOH
40 o
CO2Me
CO2Me
C
Ar
Br
2 min
Br
Br
S
O
OH
Ar SH
OH
2c
3a-f
8a-8f
2c'
O
O
O
CO2Me
CO2Me
CO2Me
O
O
O
OMe
Br
S
Br
S
Br
S
OH
OH
OH
8c (76%)
2c' (20%)
8a (70%)
2c' (13%)
8b (73%)
2c' (15%)
O
O
O
O
CO2Me
CO2Me
CO2Me
O
O
Cl
Br
Br
S
Br
S
Br
S
OH
OH
OH
8f (65%)
2c' (16%)
8e (68%)
2c' (19%)
8d (78%)
2c' (15%)
aThe reaction was carried out using 2c (1.0 mmol) and 3a–f (0.6 mmol) in
MeOH (1 mL) at –40 oC. bIsolated yield after column chromatography.
aThe reaction was carried out using 2d (1.0 mmol) and 3a–h (0.6 mmol) in
MeOH (1 mL) at –40 oC. bIsolated yield after column chromatography.
Table 4 Scope of aliphatic thiols.a,b
To support the observed regioselectivity of the reaction, we
calculated Fukui functions22 for alkenyl p-benzoquinones. These
calculations were performed with GAUSSIAN 09 program at
B3LYP/6-31** level of theory. The Fukui function for
nucleophilic attack was associated with the lowest unoccupied
+
Figure 3. Fukui functions (fk ) of alkenyl p-benzoquinones for
attack of thiol.
molecular orbital (LUMO) density. Higher the electrophilic
activation (fk ) value, greater the probability for nucleophilic
attack of thiols. There are three electrophilic sites (C-3, C-5, C-6)
+
2a
2a
2b
2b
2c
2c
R = CH2Ph
4g (70%)
4h (69%)
6g (73%)
6h (70%)
8g (70%)
8h (68%)
2a′ (12%)
2a′ (11%)
2b′ (13%)
2b′ (12%)
2c′ (13%)
2c′ (17%)
R = CH2CH2CO2Me
R = CH2Ph
available in alkenyl p-benzoquinones 2a-d for the attack of
+
R = CH2CH2CO2Me
R = CH2Ph
thiols. The calculated fk indicate that the C-3 is more
+
electrophilic (fk+ = 0.09) site than C-6 (fk+ = 0.06), and C-5 (fk
=
R = CH2CH2CO2Me
0.05) (2a, Figure 3). Similar electrophilic trend is observed in
quinones 2c and 2d. These calculated values supported our
experimental results where thiols are attached at 3rd (major) and
6th (minor) positions of alkenyl p-benzoquinones.
aThe reaction was carried out using 2a–c (1.0 mmol) and 3g,h (0.6 mmol) in
MeOH (1 mL) at –40 oC. bIsolated yield after column chromatography.
Encouraged by these results, we further employed this protocol to
the addition of various thiophenols bearing either electron-
donating groups 3b, 3c and 3d or electron-withdrawing groups 3e
and 3f with alkenyl p-benzoquinone 2d. The reaction underwent
smoothly and afforded the sole Michael addition products 9a–f in
1 min in good yield as shown in Scheme 5. This may be due to
the less electrophilicity of 2d as comparision to 2a-2b. The
reaction of 2d with aliphatic thiols 3g and 3h worked well to
Based on the above experimental results, a reasonable
mechanism for the formation of coumarin aryl sulfide derivatives
4b, 5b and cyclised product 2a′ is depicted in Scheme 3. Since
the C2-C3 double bond is in conjugation with C-1 carbonyl and
two ester groups of vinylic moiety at 2nd position and as
supported by theoretical observations (Figure 3), 3rd position of
2a is more electrophilic than 6th position. More electrophilicity of
3rd position facilitates the quick Michael attack of 4-

5
methylthiophenol (3b) to form species A (path a). Then the
4. Experimental section
4.1 General information:
ACCEPTED MANUSCRIPT
nucleophilic oxygen of hydroxy function of A attacks on the
electrophilic carbon of ester moiety to give the cyclised species B
spontaneously with the concomitant release of methanol.
Tautomerization of B produces 4b as major product. In addition
Unless otherwise noted, chemicals were purchased from the
highest purity grade available and were used without further
purification. Thin layer chromatography was performed on
Merck pre-coated 0.25 mm silica gel plates (60F-254) using UV
light as visualizing agent. Silica gel (100–200 mesh) was used for
column chromatography. IR spectra of the compounds were
recorded on FT-IR and are expressed as wave number (cm–1).
NMR spectra were recorded in CDCl3 and DMSO-d6 using TMS
as an internal standard on 500 MHz and 400 MHz instruments.
Chemical shifts (δ) were reported as parts per million (ppm) in δ
scale downfield from TMS. 1H NMR spectra were referenced to
CDCl3 (7.26 ppm) or DMSO-d6 (2.50 ppm), and 13C NMR
spectra were referenced to CDCl3 (77.0 ppm, the middle peak) or
DMSO-d6 (39.5 ppm, the middle peak). Coupling constants were
expressed in Hz. The following abbreviations were used to
explain the multiplicities: s = singlet, d = doublet, dd = doublet of
doublet, t = triplet, q = quartet, m = multiplet. High-resolution
mass spectra (HRMS) were obtained on a Brüker micrOTOF™-
Q II mass spectrometer (ESI-MS).
O
H
R
S
CO2Me
O
O
CO2Me
CO2Me
6
5
CO2Me
3
R
S
CO2Me
MeO2
C
O
O
H
O
path a
path c
2a
O
3b
R-SH
MeO
..
O
R = p-tolyl
redox process
CO2Me
H
path b
OH
CO2Me
CO2Me
S
R
RS SR
E
H
S
R
OH
OH
C
O
A
CO2Me
CO2Me
Tautomerization
O
Cyclization
MeOH
OH
O
MeO
F
.. CO2Me
CO2Me
OH
O
O
Cyclization
S
4.2 General procedure for the synthesis of aryl sulfide
R
H
S
R
derivatives of coumarins 4/5 and 6/7:
O
OH
D
CO2Me
A solution of ceric ammonium nitrate (2.5 mmol) in H2O (3
mL) was added to a solution of dimethoxy arene 1 (1 mmol) in
CH3CN (1 mL) with rapid stirring. The color changed rapidly
from orange to red. After 5 min, dichloromethane (10 mL) and
brine solution were added and the organic layer was separated.
The aqueous layer was extracted with DCM. The combined
organic layer was dried over anhyd. Na2SO4, concentrated under
reduced pressure and the residue was used further without
purification. Thus obtained benzoquinone 2 was dissolved in
O
B
Cyclization
O
Tautomerization
CO2Me
MeOH
O
O
OH
CO2Me
O
2a'
S
R
S
R
OH
o
OH
4b
MeOH (0.5 mL) at –40 C was added thiol derivative 3 (0.6
5b
mmol) in MeOH (0.5 mL) and stirred the reaction mixture for 1
min. After completion of the reaction, as checked by TLC, the
solvent was removed under vacuo and the residue was purified
by silica gel column chromatography using 30% ethyl acetate in
hexanes to furnish the pure aryl sulfide derivative of coumarin.
Major
Minor
Scheme 3. Proposed mechanism for the formation of coumarin
derivatives 4b, 5b and cyclized product 2a′
to affording 4b and 5b, the alkenyl p-benzoquinone 2a may
also undergo self-cyclisaton to produce 2a′ (path b). This
cyclization is triggered by the oxidation of thiophenol 3b by
quinone 2a to disulfide E with simultaneous reduction of 2a to
hydroquinone F, which undergoes cyclisation to form coumarin
2a′ (path b). Michael attack of 3b on the less electrophilic 6th
position of 2a leads to the formation of minor product 5b from
path c. Initial attack of thiol results in generation of intermediate
Methyl
6-hydroxy-2-oxo-5-(phenylthio)-2H-chromene-3-
carboxylate (4a): Reaction time: 1 min; Yield: 0.147 g (75%) as
o
yellow solid; mp: 167–168 C; IR (KBr): νmax 3467, 2945, 2728,
1743, 1701, 1566, 1363, 1263, 1226, 1039, 691 cm–1; H NMR
1
(500 MHz, CDCl3): δ 8.94 (s, 1H), 7.39 (AB quartet, J = 9.0,
13.5 Hz, 2H), 7.25–7.20 (m, 2H), 7.19–7.14 (m, 1H), 7.03 (d, J =
7.5 Hz, 2H), 6.89 (s, 1H), 3.88 (s, 3H) ppm; 13C NMR (125 MHz,
CDCl3): δ 163.5 (CO), 156.2 (CO), 155.2 (C), 150.2 (C), 146.6
(CH), 133.7 (C), 129.6 (CH), 126.9 (CH), 122.3 (CH), 120.6
(CH), 120.3 (CH), 118.9 (C), 113.9 (C), 52.9 (OCH3) ppm;
HRMS (ESI+): m/z calcd for C17H12O5SNa [M + Na]+: 351.0298,
found: 351.0302.
C
which immediately tautomerizes to hydroquinone D.
Cyclization of D gives the minor product 5b with the release of
MeOH.
3. Conclusion
Methyl
6-hydroxy-2-oxo-8-(phenylthio)-2H-chromene-3
In summary, we have demonstrated a concise simple, efficient
and novel approach for the generation of coumarin aryl sulfide
derivatives via regioselective Michael addition of thiols on
alkenyl p-benzoquinones in domino fashion. Thus this protocol
constitutes a straight forward route to aryl sulfide derivatives of
coumarin in good to excellent yields. As the products contain
coumarin as well as coumarin aryl sulfide moieties, these are
potential structural motifs in medicinal chemistry. The
calculation of Fukui indices on the benzoquinone derivatives
supported the obtained regioselectivity of the reaction. Further
investigations are underway in our laboratory to expand the
scope of the reactivity of these quinone synthons.
carboxylate (5a): Reaction time: 1 min; Yield: 0.029 g (15%) as
o
yellow solid; mp: 219–220 C; IR (KBr): νmax 3433, 2949, 1750,
1566, 1385, 1260, 1039, 688 cm–1; H NMR (500 MHz, DMSO-
1
d6): δ 9.96 (s, 1H), 8.71 (s, 1H), 7.49–7.46 (m, 5H), 7.11 (d, J =
2.5 Hz, 1H), 6.68 (d, J = 2.5 Hz, 1H), 3.83 (s, 3H) ppm; 13C
NMR (100 MHz, DMSO-d6): δ 163.1 (CO), 155.5 (CO), 153.9
(C), 148.9 (CH), 144.8 (C), 133.1 (CH), 130.8 (C), 130.0 (CH),
128.8 (CH), 124.9 (C), 121.5 (CH), 118.7 (C), 117.8 (C), 112.8
(CH), 52.4 (OCH3) ppm; HRMS (ESI+): m/z calcd for
C17H12O5SNa [M + Na]+: 351.0298, found: 351.0299.

6
Methyl
6-hydroxy-2-oxo-5-(4-methylphenylthio)-2H-
Methyl
6-hydroxy-8-(napthalen-2-ylthio)-2-oxo-2H-
ACCEPTED MANUSCRIPT
chromene-3-carboxylate (4b): Reaction time: 1 min; Yield: 0.150
g (73%) as yellow solid; mp: 151–152 C; IR (KBr): νmax 3383,
chromene-3-carboxylate (5d): Reaction time: 1 min; Yield: 0.041
g (18%) as yellow solid; mp: 238–239 C; IR (KBr): νmax 3429,
o
o
2954, 2907, 1753, 1707, 1567, 1261, 1228, 1026, 800, 673 cm–1;
1H NMR (500 MHz, CDCl3): δ 8.97 (s, 1H), 7.37 (AB quartet, J
= 9.5, 13.0 Hz, 2H), 7.05 (d, J = 8.0 Hz, 2H), 6.96 (d, J = 8.0 Hz,
2H), 6.88 (s, 1H), 3.90 (s, 3H), 2.26 (s, 3H) ppm; 13C NMR (125
MHz, CDCl3): δ 163.6 (CO), 156.3 (CO), 155.0 (C), 150.2 (C),
146.8 (CH), 137.3 (C), 130.4 (CH), 130.0 (C), 127.5 (CH), 122.2
(CH), 120.5 (C), 120.1 (CH), 118.8 (C), 114.7 (C), 52.9 (OCH3),
20.9 (CH3) ppm; HRMS (ESI+): m/z calcd for C18H14O5SNa [M
+ Na]+: 365.0454, found: 365.0447.
2928, 2852, 2360, 1754, 1575, 1397, 1265, 1038, 806, 591 cm–1;
1H NMR (500 MHz, DMSO-d6): δ 9.89 (s, 1H), 8.72 (s, 1H),
8.15 (s, 1H), 8.02–7.96 (m, 3H), 7.60–7.59 (m, 2H), 7.51– 7.50
(m, 1H), 7.11 (d, J = 2.5 Hz, 1H), 6.70 (d, J = 2.5 Hz, 1H), 3.83
(s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6): δ 163.0 (CO),
155.6 (CO), 154.0 (C), 149.0 (CH), 144.7 (C), 133.5 (C), 132.8
(CH), 132.6 (C), 130.0 (CH), 129.7 (CH), 128.0 (CH), 127.8
(CH), 127.7 (C), 127.2 (CH), 127.0 (CH), 125.2 (C), 121.2 (CH),
118.7 (C), 117.8 (C), 112.7 (CH), 52.5 (OCH3) ppm; HRMS
(ESI+): m/z calcd for C18H14O5SNa [M + Na]+: C21H14O5SNa [M
+ Na]+: 401.0454, found: 401.0454.
Methyl
6-hydroxy-2-oxo-8-(4-methylphenylthio)-2H-
chromene-3-carboxylate (5b): Reaction time: 1 min; Yield: 0.036
o
g (18%) as yellow solid; mp: 196–197 C; IR (KBr): νmax 3430,
Methyl
5-(4-bromophenylthio)-6-hydroxy-2-oxo-2H-
2916, 2849, 2366, 1747, 1566, 1403, 1268, 1026, 803, 641 cm–1;
1H NMR (500 MHz, DMSO-d6): δ 9.90 (s, 1H), 8.69 (s, 1H),
7.41 (d, J = 7.5 Hz, 2H), 7.31 (d, J = 7.5 Hz, 2H), 7.05 (s, 1H),
6.58 (s, 1H), 3.83 (s, 3H), 2.36 (s, 3H) ppm; 13C NMR (100
MHz, DMSO-d6): δ 163.6 (CO), 156.1 (CO), 154.4 (C), 149.5
(CH), 144.8 (C), 139.7 (C), 134.6 (CH), 131.3 (CH), 126.9 (C),
126.8 (C), 120.8 (CH), 119.0 (C), 118.3 (C), 112.6 (CH), 53.0
(OCH3), 21.3 (CH3) ppm; HRMS (ESI+): m/z calcd for
C18H14O5SNa [M + Na]+: 365.0454, found: 365.0446.
chromene-3-carboxylate (4e): Reaction time: 1 min; Yield: 0.175
g (72%) as yellow solid; mp: 182–183 C; IR (KBr): νmax 3421,
o
2946, 2849, 1757, 1566, 1315, 1247, 125, 1079, 803, 670 cm–1;
1H NMR (500 MHz, CDCl3): δ 8.90 (s, 1H), 7.43 (s, 2H), 7.37 (d,
J = 8.0 Hz, 2H), 6.90 (d, J = 8.0 Hz, 2H), 6.76 (s, 1H), 3.92 (s,
3H) ppm; 13C NMR (125 MHz, CDCl3): δ 163.5 (CO), 156.1
(CO), 155.2 (C), 150.3 (C), 146.3 (CH), 132.9 (CH), 132.7 (C),
128.4 (CH), 122.5 (CH), 121.0 (C), 120.8 (CH), 120.5 (C), 119.3
(C), 113.2 (C), 53.0 (OCH3) ppm; HRMS (ESI+): m/z calcd for
C17H11BrO5SNa [M + Na]+: 428.9403, found: 428.9404.
Methyl
6-hydroxy-5-(4-methoxyphenylthio)-2-oxo-2H-
chromene-3-carboxylate (4c): Reaction time: 1 min; Yield: 0.161
g (75%) as yellow solid; mp: 105–106 C; IR (KBr): νmax 3415,
Methyl
8-(4-bromophenylthio)-6-hydroxy-2-oxo-2H-
o
chromene-3-carboxylate (5e): Reaction time: 1 min; Yield: 0.032
2928, 2848, 1749, 1624, 1562, 1436, 1241, 1032, 815, 623 cm–1;
1H NMR (500 MHz, DMSO-d6): δ 10.40 (s, 1H), 9.00 (s, 1H),
7.40 (d, J = 9.5 Hz, 1H), 7.34 (d, J = 8.0 Hz, 1H), 7.09 (d, J = 9.0
Hz, 2H), 6.83 (d, J = 8.5 Hz, 2H), 3.80 (s, 3H), 3.68 (s, 3H) ppm;
13C NMR (125 MHz, CDCl3): δ 163.6 (CO), 156.3 (CO), 154.9
(C), 150.0 (C), 146.9 (CH), 130.0 (CH), 124.3 (C), 122.3 (CH),
120.3 (C), 119.7 (C), 119.6 (CH), 118.6 (C), 116.0 (C), 115.2
(CH), 55.3 (OCH3), 52.8 (OCH3) ppm; HRMS (ESI+): m/z calcd
for C18H14O6SNa [M + Na]+: 381.0403, found: 381.0399.
g (13%) as yellow solid; mp: 221–222 C; IR (KBr): νmax 3422,
o
2854, 2372, 1751, 1569, 1391, 1264, 1032, 841, 659 cm–1; H
1
NMR (400 MHz, DMSO-d6): δ 10.00 (s, 1H), 8.71 (s, 1H), 7.63
(d, J = 8.4 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.16 (d, J = 2.8 Hz,
1H), 6.81 (d, J = 2.8 Hz, 1H), 3.83 (s, 3H) ppm; 13C NMR (100
MHz, DMSO-d6): δ 163.0 (CO), 155.5 (CO), 153.9 (C), 148.8
(CH), 145.2 (C), 134.1 (CH), 132.8 (CH), 131.1 (C), 123.4 (C),
122.4 (CH), 121. 8 (C), 118.9 (C), 117.9 (C), 113.6 (CH), 52.4
(OCH3) ppm; HRMS (ESI+): m/z calcd for C17H11BrO5SNa [M +
Na]+: 428.9403, found: 428.9402.
Methyl
6-hydroxy-8-(4-methoxyphenylthio)-2-oxo-2H-
chromene-3-carboxylate (5c): Reaction time: 1 min; Yield: 0.032
g (15%) as yellow solid; mp: 199–200 C; IR (KBr): νmax 3420,
Methyl
5-(4-chlorophenylthio)-6-hydroxy-2-oxo-2H-
o
chromene-3-carboxylate (4f): Reaction time: 1 min; Yield: 0.154
2937, 2848, 1750, 1629, 1570, 1433, 1260, 1032, 820, 620 cm–1;
1H NMR (500 MHz, DMSO-d6): δ 9.85 (s, 1H), 8.69 (s, 1H),
7.51 (d, J = 8.5 Hz, 2H), 7.09 (d, J = 9.0 Hz, 2H), 6.99 (d, J =
2.5 Hz, 1H), 6.43 (d, J = 2.5 Hz, 1H), 3.83 (s, 3H), 3.82 (s, 3H)
ppm; 13C NMR (100 MHz, DMSO-d6): δ 163.2 (CO), 158.2
(CO), 156.1 (C), 155.7 (C), 148.9 (C), 146.5 (CH), 129.9 (CH),
126.4 (C), 123.0 (CH), 120.6 (C), 118.8 (C), 118.0 (CH), 116.2
(C), 114.9 (CH), 55.2 (OCH3), 52.6 (OCH3) ppm; HRMS (ESI+):
m/z calcd for C18H14O6SNa [M + Na]+: 381.0403, found:
381.0391.
g (71%) as yellow solid; mp: 177–178 C; IR (KBr): νmax 3355,
o
2937, 2840, 1748, 1558, 1364, 1036, 800, 610 cm–1; H NMR
1
(500 MHz, CDCl3): δ 8.90 (s, 1H), 7.41 (s, 2H), 7.21 (d, J = 8.5
Hz, 2H), 6.97 (d, J = 8.5 Hz, 2H), 6.85 (s, 1H), 3.90 (s, 3H) ppm;
13C NMR (125 MHz, CDCl3): δ 163.6 (CO), 156.2 (CO), 155.2
(C), 150.4 (C), 146.4 (CH), 133.2 (C), 132.4 (C), 129.8 (CH),
128.3 (CH), 122.6 (CH), 120.7 (CH), 120.6 (C), 119.3 (C), 113.5
(C), 53.1 (OCH3) ppm; HRMS (ESI+): m/z calcd for
C17H11ClO5SNa [M + Na]+: 384.9908, found: 384.9907.
Methyl
8-(4-chlorophenylthio)-6-hydroxy-2-oxo-2H-
Methyl 6-hydroxy-5-(napthalen-2-ylthio)-2-oxo-2H-chromene-
chromene-3-carboxylate (5f): Reaction time: 1 min; Yield: 0.028
g (13%) as yellow solid; mp: 210–211 oC; IR (KBr): νmax 3418,
2923, 2852, 2345, 1747, 1632, 1574, 1390, 1270, 1032, 832, 606
3-carboxylate (4d): Reaction time: 1 min; Yield: 0.170 g (75%)
o
as yellow solid; mp: 123–124 C; IR (KBr): νmax 3346, 2919,
1
1
2852, 2375, 1757, 1566, 1373, 1262, 1030, 829, 606 cm–1; H
cm–1; H NMR (500 MHz, DMSO-d6): δ 10.00 (s, 1H), 8.71 (s,
NMR (500 MHz, CDCl3): δ 8.99 (s, 1H), 7.78–7.72 (m, 2H), 7.64
(d, J = 7.5 Hz, 1H), 7.48–7.38 (m, 5H), 7.16 (d, J = 8.5 Hz, 1H),
6.85 (s, 1H), 3.88 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ
163.5 (CO), 156.2 (CO), 155.3 (C), 150.2 (C), 146.6 (CH), 133.6
(C), 131.9 (C), 131.1 (C), 129.5 (CH), 127.7 (CH), 127.1 (CH),
126.4 (CH), 125.4 (CH), 124.6 (CH), 122.4 (CH), 120.6 (C),
120.4 (CH), 119.0 (C), 113.8 (C), 52.9 (OCH3) ppm; HRMS
(ESI+): m/z calcd for C21H14O5SNa [M + Na]+: 401.0454, found:
401.0451.
1H), 7.52 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 8.0 Hz, 2H), 7.15 (d, J
= 2.0 Hz, 1H), 6.77 (d, J = 1.5 Hz, 1H), 3.82 (s, 3H) ppm; 13C
NMR (100 MHz, DMSO-d6): δ 163.1 (CO), 155.5 (CO), 153.9
(C), 148.9 (CH), 145.2 (C), 134.1 (CH), 133.5 (C), 130.5 (C),
129.9 (CH), 123.8 (CH), 122.2 (C), 118.9 (C), 118.0 (C), 113.4
(CH), 52.5 (OCH3) ppm; HRMS (ESI+): m/z calcd for
C17H11ClO5SNa [M + Na]+: 384.9908, found: 384.9906.
Methyl
5-(benzylthio)-6-hydroxy-2-oxo-2H-chromene-3-
carboxylate (4g): Reaction time: 2 min; Yield: 0.144 g (70 %) as
o
yellow solid; mp: 121–122 C; IR (KBr): νmax 3403, 2919, 1748,

7
1
1633, 1559, 1312, 1224, 1044, 709, 600 cm–1; H NMR (500
(CH), 130.2 (C), 127.7 (CH), 122.0 (CH), 120.5 (C), 120.0
ACCEPTED MANUSCRIPT
MHz, CDCl3): δ 8.42 (s, 1H), 7.29 (AB quartet, J = 9.0, 11.6 Hz,
2H), 7.18–7.13 (m, 3H), 6.90 (d, J = 7.0 Hz, 2H), 6.84 (s, 1H),
3.92 (s, 3H), 3.82 (s, 2H) ppm; 13C NMR (125 MHz, CDCl3): δ
163.4 (CO), 156.3 (CO), 155.0 (C), 150.0 (C), 146.6 (CH), 136.0
(C), 128.8 (CH), 128.7 (CH), 127.8 (CH), 121.2 (CH), 119.5
(CH), 117.8 (C), 115.4 (C), 52.7 (OCH3), 40.9 (CH2) ppm;
HRMS (ESI+): m/z calcd for C18H14O5SNa [M + Na]+: 365.0454,
found : 365.0453.
(CH), 119.3 (C), 114.8 (C), 62.0 (CH2), 20.9 (OCH3), 14.0 (CH3)
ppm; HRMS (ESI+): m/z calcd for C19H16O5SNa [M + Na]+:
379.0611, found: 379.0606.
Ethyl 6-hydroxy-2-oxo-8-(4-methylphenylthio)-2H-chromene-
3-carboxylate (7b): Reaction time: 1 min; Yield: 0.036 g (17%)
o
as yellow solid; mp: 207–208 C; IR (KBr): νmax 3469, 2920,
1745, 1569, 1460, 1390, 1250, 1229, 1130, 679 cm–1; H NMR
1
(500 MHz, DMSO-d6): δ 9.93 (s, 1H), 8.66 (s, 1H), 7.41 (d, J =
8.0 Hz, 2H), 7.31 (d, J = 7.5 Hz, 2H), 7.04 (d, J = 2.5 Hz, 1H),
6.56 (d, J = 2.5 Hz, 1H), 4.28 (q, J = 7.5 Hz, 2H), 2.35 (s, 3H),
1.30 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (100 MHz, DMSO-d6): δ
162.9 (CO), 156.1 (CO), 154.2 (C), 148.9 (CH), 144.6 (C), 139.5
(C), 134.2 (CH), 131.1 (CH), 126.7 (C), 126.4 (C), 120.8 (CH),
118.8 (C), 118.4 (C), 112.4 (CH), 61.7 (CH2), 21.0 (OCH3), 14.3
(CH3) ppm; HRMS (ESI+): m/z calcd for C19H16O5SNa [M +
Na]+: 379.0611, found: 379.0606.
Methyl 6-hydroxy-5-(3-methoxy-3-oxopropylthio)-2-oxo-2H-
chromene-3-carboxylate (4h): Reaction time: 2 min; Yield: 0.139
o
g (69%) as yellow solid; mp: 108–109 C; IR (KBr): νmax 3469,
2922, 1742, 1698, 1565, 1465, 1377, 1256, 1224, 1035, 676 cm–
1; 1H NMR (400 MHz, CDCl3): δ 9.00 (s, 1H), 7.40 (s, 1H), 7.27
(AB quartet, J = 9.2, 15.6 Hz , 2H), 3.90 (s, 3H), 3.66 (s, 3H),
2.92 (t, J = 6.8 Hz, 2H), 2.51 (t, J = 6.8 Hz, 2H) ppm; 13C NMR
(100 MHz, CDCl3): δ 171.8 (CO), 163.4 (CO), 156.4 (CO), 155.6
(C), 149.3 (C), 147.1 (CH), 122.3 (CH), 120.5 (C), 118.4 (CH),
117.6 (C), 116.2 (C), 52.6 (OCH3), 51.7 (OCH3), 33.5 (CH2),
30.1 (CH2) ppm; HRMS (ESI+): m/z calcd for C15H14O7SNa [M
+ Na]+: 361.0352, found: 361.0355.
Ethyl
6-hydroxy-7-(4-methoxyphenylthio)-2-oxo-2H-
chromene-3-carboxylate (6c): Reaction time: 1 min; Yield: 0.174
o
g (78%) as yellow solid; mp: 153–154 C; IR (KBr): νmax 3419,
2923, 1754, 1683, 1565, 1492, 1380, 1267, 1033, 797, 608 cm–1;
1H NMR (500 MHz, CDCl3): δ 8.98 (s, 1H), 7.33 (AB quartet, J
= 9.0, 18.5 Hz, 2H), 7.08 (d, J = 8.5 Hz, 2H), 6.77 (d, J = 9.0 Hz,
2H), 4.37 (q, J = 7.0 Hz, 2H), 3.72 (s, 3H), 1.37 (t, J = 7.0 Hz,
3H) ppm; 13C NMR (125 MHz, CDCl3): δ 163.0 (CO), 159.2
(CO), 156.2 (C), 154.7 (C), 150.1 (C), 146.3 (CH) 130.2 (CH),
124.2 (C), 122.0 (CH), 120.3 (C), 119.8 (CH), 119.1 (C), 116.0
(C), 115.3 (CH), 62.0 (C), 55.3 (CH2), 14.1 (CH3) ppm; HRMS
(ESI+): m/z calcd for C19H16O6SNa [M + Na]+: 395.0560, found:
395.0565.
Methyl 6-hydroxy-2-oxo-2H-chromene-3-carboxylate (2a′):
o
mp: 195–196 C; IR (KBr): νmax 3437, 2928, 2369, 1731, 1569,
1
1486, 1378, 1026, 800 cm–1; H NMR (500 MHz, DMSO-d6): δ
9.95 (s, 1H), 8.69 (s, 1H), 7.28 (d, J = 9.0 Hz, 1H), 7.21 (d, J =
3.0 Hz, 1H), 7.16 (dd, J = 3.0, 9.0 Hz, 1H), 3.82 (s, 3H) ppm; 13C
NMR (100 MHz, DMSO- d6): δ 163.2 (CO), 156.8 (CO), 153.8
(C), 148.8 (C), 148.8 (CH), 148.2 (C), 122.9 (CH), 117.7 (C),
116.9 (CH), 113.0 (CH), 52.2 (OCH3) ppm; HRMS (ESI+): m/z
calcd for C11H8O5Na [M + Na]+: 243.0263, found : 243.0133.
Ethyl
6-hydroxy-2-oxo-5-(phenylthio)-2H-chromene-3-
Ethyl
6-hydroxy-8-(4-methoxyphenylthio)-2-oxo-2H-
carboxylate (6a): Reaction time: 1 min; Yield: 0.162 g (79%) as
chromene-3-carboxylate (7c): Reaction time: 1 min; Yield: 0.028
o
o
yellow solid; mp: 132–133 C; IR (KBr): νmax 3165, 1740, 1676,
g (13%) as yellow solid; mp: 191–192 C; IR (KBr): νmax 3424,
1
1
1561, 1453, 1306, 1229, 1135, 1045, 797, 726 cm–1; H NMR
2924, 1701, 1573, 1438, 1383, 1266, 1098 cm–1; H NMR (500
(500 MHz, CDCl3): δ 8.92 (s, 1H), 7.42 (s, 2H), 7.28–7.24 (m,
2H), 7.22–7.20 (m, 1H), 7.06 (d, J = 7.5 Hz, 2H), 7.05 (s, 1H),
4.37 (q, J = 7.0 Hz, 2H), 1.37 (t, J = 7.0 Hz, 3H) ppm; 13C NMR
(125 MHz, CDCl3): δ 163.0 (CO), 156.3 (CO), 155.1 (C), 150.2
(C), 146.1 (CH), 133.8 (C), 129.6 (CH), 127.1 (CH), 127.0 (CH),
122.1 (CH), 120.6 (C), 120.3 (CH), 119.4 (C), 113.9 (C), 62.0
(CH2), 14.1 (CH3) ppm; HRMS (ESI+): m/z calcd for
C18H14O5SNa [M + Na]+: 365.0454, found: 365.0460.
MHz, DMSO-d6): δ 9.88 (s, 1H), 8.65 (s, 1H), 7.51 (d, J = 9.0
Hz, 2H), 7.09 (d, J = 8.5 Hz, 2H), 6.99 (d, J = 2.5 Hz, 1H), 6.44
(d, J = 3.0 Hz, 1H), 4.28 (q, J = 7.0 Hz, 2H), 3.81 (s, 3H), 1.30 (t,
J = 7.0 Hz, 3H) ppm; 13C NMR (100 MHz, DMSO-d6): 163.5
(CO), 161.2 (CO), 156.8 (C), 154.5 (C), 149.6 (CH), 144.5 (C),
137.6 (CH), 128.5 (C), 120.1 (C), 119.9 (CH), 119.0 (C), 118.6
(C), 116.6 (CH), 112.0 (CH), 62.4 (CH2), 56.1 (OCH3), 14.7
(CH3) ppm. HRMS (ESI+): m/z calcd for C19H17O6S [M + H]+:
373.0740, found: 373.0741.
Ethyl
6-hydroxy-2-oxo-8-(phenylthio)-2H-chromene-3-
carboxylate (7a): Reaction time: 1 min; Yield: 0.024 g (12%) as
Ethyl 6-hydroxy-5-(napthalen-2-ylthio)-2-oxo-2H-chromene-
o
yellow solid; mp: 147–148 C; IR (KBr): νmax 3400, 3058, 2925,
3-carboxylate (6d): Reaction time: 1 min; Yield: 0.176 g (75%)
1
o
1748, 1571, 1444, 1385, 1268, 1034, 800, 735 cm–1; H NMR
as yellow solid; mp: 179 C; IR (KBr): νmax 3414, 2920, 1749,
1
(500 MHz, DMSO-d6): δ 9.96 (s, 1H), 8.67 (s, 1H), 7.47–7.46
(m, 5H), 7.10 (s, 1H), 6.69 (s, 1H), 4.29 (q, J = 7.0 Hz, 2H), 1.30
(t, J = 7.0 Hz, 3H) ppm; 13C NMR (100 MHz, DMSO-d6): δ
162.6 (CO), 155.7 (CO), 154.0 (C), 148.6 (CH), 144.8 (C), 133.1
(CH), 130.8 (CH), 130.1 (C), 128.9 (CH), 124.9 (C), 121.5 (CH),
118.8 (C), 118.2 (C), 112.8 (CH), 61.3 (CH2), 14.1 (CH3) ppm;
HRMS (ESI+): m/z calcd for C18H14O5SNa [M + Na]+: 365.0454,
found: 365.0454.
1570, 1459, 1382, 1252, 1038, 800, 672 cm–1; H NMR (500
MHz, CDCl3): δ 8.93 (s, 1H), 7.74–7.69 (m, 2H), 7.62 (d, J = 7.5
Hz, 1H), 7.45–7.36 (m, 5H), 7.15 (d, J = 8.5 Hz, 1H), 4.32 (q, J =
7.0 Hz, 2H), 1.31 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (125 MHz,
CDCl3): δ 162.9 (CO), 156.3 (CO), 155.2 (C), 150.2 (C), 146.1
(CH), 133.6 (C), 131.9 (C), 131.2 (C), 129.5 (CH), 127.7 (CH),
127.1 (CH), 126.4 (CH), 125.6 (CH), 125.6 (CH), 124.8 (CH),
122.2 (CH), 120.6 (C), 120.3 (CH), 119.4 (C), 113.9 (C), 62.0
(CH2), 14.0 (CH3) ppm; HRMS (ESI+): m/z calcd for
C22H16O5SNa [M + Na]+: 415.0611, found: 415.0612.
Ethyl 6-hydroxy-2-oxo-5-(4-methylphenylthio)-2H-chromene-
3-carboxylate (6b): Reaction time: 1 min; Yield: 0.160 g (75%)
o
as yellow solid; mp: 108–109 C; IR (KBr): νmax 3469, 2922,
Ethyl 6-hydroxy-8-(napthalen-2-ylthio)-2-oxo-2H-chromene-
1
1742, 1698, 1565, 1465, 1377, 1256, 1224, 1035, 676 cm–1; H
3-carboxylate (7d): Reaction time: 1 min; Yield: 0.040 g (17%)
o
NMR (500 MHz, CDCl3): δ 8.93 (s, 1H), 7.37 (AB quartet, J =
9.0, 11.0 Hz, 2H), 7.05 (d, J = 7.5 Hz, 2H), 6.98 (d, J = 7.5 Hz,
2H), 6.86 (s, 1H), 4.36 (q, J = 7.0 Hz, 2H), 2.26 (s, 3H), 1.36 (t, J
= 7.0 Hz, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ 163.0 (CO),
156.3 (CO), 154.9 (C), 150.1 (C), 146.2 (CH), 137.3 (C), 130.4
as yellow solid; mp: 230–231 C; IR (KBr): νmax 3414, 2918,
1
1749, 1570, 1462, 1382, 1250, 1038, 800, 658 cm–1; H NMR
(500 MHz, DMSO-d6): δ 9.92 (s, 1H), 8.68 (s, 1H), 8.14 (s, 1H),
8.03–7.95 (m, 3H), 7.60–7.57 (m, 2H), 7.50 (dd, J = 1.0, 8.5 Hz,
1H), 7.10 (d, J = 2.5 Hz, 1H), 6.70 (d, J = 2.5 Hz, 1H), 4.29 (q, J

8
= 6.5 Hz, 2H), 1.30 (t, J = 7.5 Hz, 3H) ppm; 13C NMR (100
MHz, DMSO-d6): 162.6 (CO), 156.4 (CO), 155.7 (C), 149.1 (C)
146.0 (CH) ,134.0 (C), 133.3 (C), 131.2 (C), 128.8 (CH), 127.7
(CH), 127.0 (CH), 126.9 (CH), 125.8 (CH), 125.2 (CH), 124.5
(CH), 123.1 (CH), 120.9 (C), 119.4 (C), 118.4 (CH), 114.1 (C),
61.4 (CH2), 14.0 (CH3) ppm; HRMS (ESI+): m/z calcd for
C22H16O5SNa [M + Na]+: 415.0611, found: 415.0610.
MHz, CDCl3): δ 162.8 (CO), 156.3 (CO), 154.9 (C), 149.4 (C),
ACCEPTED MANUSCRIPT
146.1 (CH), 136.0 (C), 128.8 (CH), 128.6 (CH), 127.8 (CH),
121.3 (CH), 121.1 (C), 119.4 (CH), 118.1 (C), 115.4 (C), 61.7
(CH2), 40.7 (CH2), 14.2 (CH3) ppm; HRMS (ESI+): m/z calcd for
C19H16O5SNa [M + Na]+: 379.0611, found : 379.0611.
Ethyl-6–hydroxy-5-(3-methoxy-3-oxopropylthio)-2-oxo-2H-
chromene-3-carboxylate (6h): Reaction time: 2 min; Yield: 0.148
g (70%) as yellow solid; mp: 114–115 C; IR (KBr): νmax 3246,
o
Ethyl 5-(4-bromophenylthio)-6-hydroxy-2-oxo-2H-chromene-
3-carboxylate (6e): Reaction time: 1 min; Yield: 0.197 g (78%)
2946, 1742, 1697, 1561, 1366, 1251, 1161, 1041, 835, 667 cm–1;
1H NMR (500 MHz, CDCl3): δ 9.02 (s, 1H), 7.42 (s, 1H), 7.32
(AB quartet, J = 9.0, 11.0 Hz, 2H), 4.43 (q, J = 7.5 Hz, 2H), 3.73
(s, 3H), 2.98 (t, J = 6.5 Hz, 2H), 2.57 (t, J = 6.5 Hz, 2H), 1.42 (t,
J = 7.0 Hz, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ 171.9
(CO), 163.0 (CO), 156.4 (CO), 155.4 (C), 149.7 (CH), 146.3 (C),
122.0 (CH), 120.5 (C), 119.3 (CH), 118.8 (C), 115.7 (C), 61.9
(CH2), 52.0 (OCH3), 33.2 (CH2), 31.1 (CH2), 14.0 (CH3) ppm;
HRMS (ESI+): m/z calcd for C16H16O7SNa [M + Na]+: 375.0509,
found : 375.0507.
o
as yellow solid; mp: 160–161 C; IR (KBr): νmax 3423, 2921,
1
1750, 1566, 1381, 1229, 1035, 802, 659 cm-1; H NMR (500
MHz, CDCl3): δ 8.85 (s, 1H), 7.41 (s, 2H), 7.37 (d, J = 8.5 Hz,
2H), 6.92 (d, J = 8.5 Hz, 2H), 6.73 (s, 1H), 4.38 (q, J = 7.0 Hz,
2H), 1.37 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (125 MHz, CDCl3):
δ 162.9 (CO), 156.1 (CO), 155.1 (C), 150.2 (C), 145.8 (CH),
133.1 (C), 132.6 (CH), 128.5 (CH), 122.3 (CH), 120.9 (C), 120.6
(CH), 120.5 (C), 119.6 (C), 113.3 (C), 62.1 (CH2), 14.0 (CH3)
ppm; HRMS (ESI+): m/z calcd for C18H14BrO5S [M + H]+:
420.9739, found: 420.9753.
Ethyl 6-hydroxy-2-oxo-2H-chromene-3-carboxylate (2b′): mp:
174–175 oC; IR (KBr): νmax 3333, 2922, 1744, 1572, 1256, 1386,
Ethyl 8-(4-bromophenylthio)-6-hydroxy-2-oxo-2H-chromene-
1
3-carboxylate (7e): Reaction time: 1 min; Yield: 0.025 g (10%)
1184, 1038, 797, 670 cm–1; H NMR (400 MHz, DMSO-d6): δ
o
as yellow solid; mp: 221–222 C; IR (KBr): νmax 3421, 2946,
9.92 (s, 1H), 8.65 (s, 1H), 7.28 (d, J = 8.8 Hz, 1H), 7.20–7.14
(m, 2H), 4.27 (q, J = 7.2 Hz, 2H), 1.29 (t, J = 6.4 Hz, 3H) ppm;
13C NMR (100 MHz, DMSO-d6): δ 162.8 (CO), 156.3 (CO),
154.0 (C), 148.4 (CH), 147.9 (C), 122.7 (CH), 118.3 (C), 117.8
(CH), 117.1 (C), 113.8 (CH), 61.2 (CH2), 14.1 (CH3) ppm;
HRMS (ESI+): m/z calcd for C12H10O5Na[M + Na]+: 257.0420,
found: 257.0430.
1
2849, 1757, 1566, 1315, 1247, 1079, 803, 670 cm-1; H NMR
(500 MHz, DMSO-d6): δ 10.00 (s, 1H), 8.69 (s, 1H), 7.64 (d, J =
8.0 Hz, 2H), 7.38 (d, J = 8.0 Hz, 2H), 7.16 (s, 1H), 6.80 (s, 1H),
4.29 (q, J = 7.0 Hz, 2H), 1.30 (t, J = 7.0 Hz, 3H) ppm; 13C NMR
(100 MHz, DMSO-d6): δ 162.6 (CO), 155.6 (CO), 154.0 (C),
148.6 (CH), 145.3 (C), 134.2 (CH), 132.9 (CH), 131.2 (C), 123.5
(C), 122.4 (CH), 121.9 (C), 119.0 (C), 118.3 (C), 113.6 (CH),
61.4 (CH2), 14.1 (CH3) ppm; HRMS (ESI+): m/z calcd for
C18H14BrO5S [M + H]+: 420.9739, found: 420.9740.
4.3 General procedure for the synthesis of aryl sulfide
derivatives of coumarins 8a–h:
Ethyl 5-(4-chlorophenylthio)-6-hydroxy-2-oxo-2H-chromene-
3-carboxylate (6f): Reaction time: 1 min; Yield: 0.169 g (75%)
The diaryl sulfides 8a–h were synthesized according to the
procedure described for the synthesis of compounds 4/5.
o
as yellow solid; mp: 156–157 C; IR (KBr): νmax 3432, 2931,
1
1749, 1632, 1570, 1470, 1370, 1229, 1035, 805 cm–1; H NMR
Methyl
7-bromo-6-hydroxy-2-oxo-5-(phenylthio)-2H-
(500 MHz, CDCl3): δ 8.87 (s, 1H), 7.41 (s, 2H), 7.23 (d, J = 8.5
Hz, 2H), 6.99 (d, J = 8.5 Hz, 2H), 6.79 (s, 1H), 4.37 (q, J = 7.5
Hz, 2H), 1.37 (t, J = 7.0 Hz, 3H) ppm; 13C NMR (125 MHz,
CDCl3): δ 163.0 (CO), 156.1 (CO), 155.1 (C), 150.2 (C), 145.9
(CH), 133.1 (C), 132.3 (C), 129.8 (CH), 128.3 (CH), 122.3 (CH),
120.6 (CH), 120.4 (C), 119.6 (C), 113.4 (C), 62.2 (CH2), 14.1
(OCH3) ppm; HRMS (ESI+): m/z calcd for C18H13ClO5SNa [M +
Na]+: 399.0064, found: 399.0060.
chromene-3-carboxylate (8a): Reaction time: 2 min; Yield: 0.170
o
g (70%) as yellow solid; mp: 179–180 C; IR (KBr): νmax 3414,
2922, 1771, 1622, 1550, 1415, 1318, 1203, 1041, 806, 617 cm-1;
1H NMR (500 MHz, CDCl3): δ 8.91 (s, 1H), 7.70 (s, 1H), 7.30–
7.22 (m, 3H), 7.08 (d, J = 7.5 Hz, 2H), 7.04 (s, 1H), 3.92 (s, 3H)
ppm; 13C NMR (125 MHz, CDCl3): δ 163.4 (CO), 155.6 (CO),
152.3 (C), 149.5 (C), 146.4 (CH), 133.0 (C), 129.8 (CH), 127.6
(CH), 127.5 (CH), 123.5 (CH), 120.1 (C), 119.4 (C), 117.0 (C),
115.4 (C), 53.0 (OCH3) ppm; HRMS (ESI+): m/z calcd for
C17H11BrO5SNa [M + Na]+: 428.9403, found: 428.9402.
Ethyl 8-(4-chlorophenylthio)-6-hydroxy-2-oxo-2H-chromene-
3-carboxylate (7f): Reaction time: 1 min; Yield: 0.025 g (11%)
o
as yellow solid; mp: 233–234 C; IR (KBr): νmax 3366, 2934,
2857, 1748, 1573, 1477, 1444, 1388, 1270, 1035, 812, 644 cm–1;
1H NMR (500 MHz, DMSO-d6): δ 10.00 (s, 1H), 8.68 (s, 1H),
7.51 (d, J = 8.5 Hz, 2H), 7.45 (d, J = 8.0 Hz, 2H), 7.14 (d, J = 2.5
Hz, 1H), 6.77 (d, J = 2.5 Hz, 1H), 4.28 (q, J = 7.0 Hz, 2H), 1.30
(t, J = 7.0 Hz, 3H) ppm; 13C NMR (125 MHz, DMSO-d6): δ
162.7 (CO), 155.9 (CO), 153.9 (C), 148.3 (CH), 145.4 (C), 134.8
(CH), 134.5 (C), 129.9 (CH), 129.7 (C), 129.5 (C), 125.9 (C),
122.3 (CH), 118.1 (C), 111.9 (CH), 61.6 (CH2), 13.9 (CH3) ppm;
HRMS (ESI+): m/z calcd for C18H13ClO5SNa [M + Na]+:
399.0064, found: 399.0064.
Methyl 7-bromo-6-hydroxy-2-oxo-5-(4-methylphenylthio)-2H-
chromene-3-carboxylate (8b): Reaction time: 2 min; Yield: 0.184
o
g (73%) as yellow solid; mp: 167–168 C; IR (KBr): νmax 3414,
2922, 1771, 1622, 1550, 1415, 1318, 1203, 1041, 806, 617 cm–1;
1H NMR (500 MHz, CDCl3): δ 8.95 (s, 1H), 7.67 (s, 1H), 7.09 (d,
J = 8.0 Hz, 2H), 7.08 (s, 1H), 7.02 (d, J = 8.0 Hz, 2H), 3.92 (s,
3H), 2.29 (s, 3H) ppm; 13C NMR (125 MHz, CDCl3): δ 163.4
(CO), 155.7 (CO), 152.2 (C), 149.4 (C), 146.5 (CH), 138.0 (C),
130.6 (CH), 129.4 (C), 128.2 (CH), 123.2 (CH), 120.0 (C), 119.2
(C), 117.0 (C), 116.3 (C), 53.0 (OCH3), 21.0 (CH3) ppm; HRMS
(ESI+): m/z calcd for C18H13BrO5SNa [M + Na]+: 442.9559,
found: 442.9559.
Ethyl
7-(benzylthio)-6-hydroxy-2-oxo-2H-chromene-3-
carboxylate (6g): Reaction time: 2 min; Yield: 0.156 g (73 %) as
o
Methyl 7-bromo-6-hydroxy-5-(4-methoxyphenylthio)-2-oxo-
yellow solid; mp: 110–111 C; IR (KBr): νmax 3369, 2925, 1752,
1
1563, 1468, 1383, 1248, 1041, 803, 703 cm–1; H NMR (500
2H-chromene-3-carboxylate (8c): Reaction time: 2 min; Yield:
o
0.199 g (76%) as yellow solid; mp: 187–188 C; IR (KBr): νmax
MHz, CDCl3): δ 8.39 (s, 1H), 7.28 (AB quartet, J = 9.0, 12.5 Hz,
2H), 7.17–7.10 (m, 3H), 6.90–6.85 (m, 3H), 4.37 (q, J = 7.0 Hz,
2H), 3.82 (s, 2H), 1.41 (t, J = 7.5 Hz, 3H) ppm; 13C NMR (125
1
3417, 2924, 1702, 1571, 1498, 1374, 1266, 1028, 803 cm–1; H
NMR (500 MHz, CDCl3): 9.01 (s, 1H), 7.63 (s, 1H), 7.17–7.13
(m, 2H), 6.81 (d, J = 9.0 Hz, 2H), 3.94 (s, 3H), 3.76 (s, 3H) ppm;

9
13C NMR (125 MHz, CDCl3): δ 163.4 (CO), 159.7 (CO), 155.7
(ESI+): m/z calcd for C15H13BrO7SNa [M + Na]+: 438.9458,
found: 438.9456.
ACCEPTED MANUSCRIPT
(C), 151.9 (C), 149.4 (C), 146.6 (CH), 130.9 (CH), 123.3 (C),
123.0 (CH), 119.8 (C), 119.0 (C), 117.5 (C), 117.0 (C), 115.5
(CH), 55.4 (OCH3), 53.0 (OCH3) ppm; HRMS (ESI+): m/z calcd
for C18H13BrO6SNa [M + Na]+: 458.9508, found: 458.9509.
Methyl
7-bromo-6-hydroxy-2-oxo-2H-chromene-3-
o
carboxylate (2c′): mp: 214–215 C; IR (KBr): νmax 3343, 2920,
1746, 1572, 1348 ,1180, 1038, 760, 670 cm–1; H NMR (500
1
Methyl 7-bromo-6-hydroxy-5-(napthalen-2-ylthio)-2-oxo-2H-
MHz, DMSO-d6): δ 10.80 (s, 1H), 8.71 (s, 1H), 7.71 (s, 1H), 7.34
(s, 1H) 3.82 (s 3H) ppm; 13C NMR (125 MHz, DMSO-d6): δ
163.2 (CO), 155.8 (CO), 151.0 (C), 148.4 (CH), 147.6 (C), 120.4
(CH), 117.8 (C), 117.6 (C) 117.5 (C), 114.0 (CH), 52.4 (OCH3)
ppm; HRMS (ESI+): m/z calcd for C11H7BrO5Na [M + Na]+:
320.9370, found: 320.9370.
chromene-3-carboxylate (8d): Reaction time: 2 min; Yield: 0.214
o
(78%) as yellow solid; mp: 193–194 C; IR (KBr): νmax 3437,
1
2928, 1731, 1569, 1486, 1378, 1178, 1026, 800, 635 cm–1; H
NMR (500 MHz, CDCl3): δ 8.96 (s, 1H), 7.78–7.74 (m, 2H),
7.70–7.65 (m, 2H), 7.52–7.45 (m, 3H), 7.16 (dd, J = 1.5, 8.5 Hz,
1H), 7.12 (s, 1H), 3.89 (s, 3H) ppm; 13C NMR (125 MHz,
CDCl3): δ 163.3 (CO), 155.6 (CO), 152.4 (C), 149.5 (C), 146.3
(CH), 133.6 (C), 132.2 (C), 130.3 (C) 129.8 (CH), 127.8 (CH),
127.3 (CH), 127.2 (CH), 126.7 (CH), 126.4 (CH), 125.0 (CH),
123.5 (CH), 120.2 (C), 119.3 (C), 117.2 (C), 115.5 (C), 53.0
(OCH3) ppm; HRMS (ESI+): m/z calcd for C21H13BrO5SNa [M +
Na]+: 478.9559, found: 478.9559.
4.4 General procedure for the synthesis of aryl sulfide
derivatives of alkenyl hydroquinone 9a–h:
The diaryl sulfides 9a–h were synthesized according to the
procedure described for the synthesis of compounds 4/5.
Methyl
(E)-3-(3,6-dihydroxy-2-(phenylthio)phenyl)acrylate
Methyl 7-bromo-5-(4-bromophenylthio)-6-hydroxy-2-oxo-2H-
(9a): Reaction time: 1 min; Yield: 0.123 g (68%) as brown solid;
chromene-3-carboxylate (8e): Reaction time: 2 min; Yield: 0.198
o
o
mp: 205–206 C; IR (KBr): νmax 3344, 1685, 1626, 1438, 1338,
g (68%) as yellow solid; mp: 204–205 C; IR (KBr): νmax 3414,
1265, 1170, 824, 646 cm–1; H NMR (400 MHz, DMSO-d6): δ
1
1
2945, 1762, 1622, 1542, 1453, 1244, 1032, 812, 620 cm–1; H
10.12 (s, 1H), 9.35 (s, 1H), 8.22 (d, J = 16.0 Hz, 1H), 7.22 (t, J =
7.6 Hz, 2H), 7.08 (t, J = 7.6 Hz, 1H), 7.00–6.91 (m, 5H), 3.64 (s,
3H) ppm; 13C NMR (100 MHz, DMSO-d6): δ 167.6 (CO), 152.2
(C), 151.5 (C), 140.3 (CH), 137.6 (C), 129.0 (CH), 125.9 (CH),
125.0 (C) 123.6, (CH), 121.7 (CH), 119.2 (CH), 118.7 (CH),
117.2 (C), 51.3 (OCH3) ppm; HRMS (ESI+): m/z calcd for
C16H14O4SNa [M + Na]+: 325.0505, found: 325.0519.
NMR (500 MHz, CDCl3): δ 8.88 (s, 1H), 7.70 (s, 1H), 7.40 (d, J
= 8.5 Hz, 2H), 6.95 (d, J = 8.5 Hz, 2H), 3.93 (s, 3H) ppm; 13C
NMR (125 MHz, CDCl3): δ 163.3 (CO), 155.5 (CO), 152.3 (C),
149.6 (C), 146.0 (CH), 132.9 (CH), 132.3 (C), 129.0 (CH), 123.7
(CH), 121.6 (C), 120.0 (C), 119.6 (C), 117.2 (C), 114.9 (C), 53.0
(OCH3) ppm; HRMS (ESI+): m/z calcd for C17H10Br2O5SNa [M
+ Na]+: 506.8508, found: 506.8507.
Methyl 7-bromo-5-(4-chlorophenylthio)-6-hydroxy-2-oxo-2H-
chromene-3-carboxylate (8f): Reaction time: 2 min; Yield: 0.172
Methyl (E)-3-(3,6-dihydroxy-2-(4-methylthio)phenyl)acrylate
o
g (65%) as yellow solid; mp: 206–207 C; IR (KBr): νmax 3411,
(9b): Reaction time: 1 min; Yield: 0.132 g (70%) as brown solid;
1
2925, 1770, 1700, 1622, 1550, 1182, 1035, 797, 617 cm–1; H
o
mp: 205–206 C; IR (KBr): νmax 3326, 2919, 1686, 1628, 1433,
1
1338, 1264, 1195, 808, 643 cm–1; H NMR (400 MHz, DMSO-
NMR (500 MHz, CDCl3): δ 8.81 (s, 1H), 7.63 (s, 1H), 7.18 (d, J
= 8.5 Hz, 2H), 6.95 (d, J = 8.5 Hz, 2H), 6.89 (s, 1H), 3.86 (s, 3H)
ppm; 13C NMR (125 MHz, CDCl3): δ 163.3 (CO), 155.5 (CO),
152.2 (C), 149.5 (C), 146.1 (CH), 133.6 (C), 131.6 (C), 129.9
(CH), 128.8 (CH), 123.6 (CH), 120.0 (C), 119.4 (C), 117.3 (C),
115.0 (C), 53.1 (OCH3) ppm; HRMS (ESI+): m/z calcd for
C17H10BrClO5SNa [M + Na]+: 462.9013, found: 462.9012.
d6): δ 10.10 (s, 1H), 9.30 (s, 1H), 8.23 (d, J = 16.0 Hz, 1H), 7.04
(d, J = 8.0 Hz, 2H), 6.98–6.91 (m, 3H), 6.90–6.86 (m, 2H), 3.65
(s, 3H), 2.20 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-d6): δ
167.6 (CO), 152.0 (C), 151.4 (C), 140.4 (CH), 134.5 (C), 133.9
(C), 129.6 (CH), 126.3 (C), 123.5 (CH), 121.5 (CH), 119.0 (CH),
118.6 (CH), 118.0 (C) 51.3 (OCH3), 20.4 (CH3) ppm; HRMS
(ESI+): m/z calcd for C17H17O4S [M + H]+: 317.0842, found:
317.0853.
Methyl
5-(benzylthio)-7-bromo-6-hydroxy-2-oxo-2H-
chromene-3-carboxylate (8g): Reaction time: 2 min; Yield: 0.176
o
g (70%) as yellow solid; mp: 167–168 C; IR (KBr): νmax 3455,
Methyl
(E)-3-(3,6-dihydroxy-2-(4-
2925, 1758, 1633, 1553, 1399, 1240, 1140, 1039, 879, 656 cm–1;
1H NMR (500 MHz, CDCl3): δ 8.30 (s, 1H), 7.54 (s, 1H), 7.20 (s,
1H), 7.14–7.12 (m, 3H), 6.89 (d, J = 7.0 Hz, 2H), 3.89 (s, 3H),
3.86 (s, 2H) ppm; 13C NMR (125 MHz, CDCl3): δ 163.1 (CO),
155.7 (CO), 152.2 (C), 148.7 (C), 146.3 (CH), 135.6 (C), 128.8
(CH), 128.7 (CH), 127.9 (CH), 122.6 (CH), 120.7 (C), 117.8 (C),
116.6 (C), 116.0 (C), 52.7 (OCH3), 40.8 (CH2) ppm; HRMS
(ESI+): m/z calcd for C18H13BrO5SNa [M + Na]+: 442.9559,
found: 442.9561.
methoxyphenylthio)phenyl)acrylate (9c): Reaction time: 1 min;
o
Yield: 0.143 g (72%) as light brown solid; mp: 182–183 C; IR
(KBr): νmax 3394, 1679, 1629, 1497, 1436, 1339, 1271, 820, 518
1
cm–1; H NMR (400 MHz, DMSO-d6): δ 10.00 (s, 1H), 9.24 (s,
1H), 8.31 (d, J = 16.0 Hz, 1H), 7.00 (d, J = 8.8 Hz, 2H), 6.94–
6.88 (m, 3H), 6.83 (d, J = 8.8 Hz, 2H), 3.68 (s, 3H), 3.67 (s, 3H)
ppm; 13C NMR (100 MHz, DMSO-d6): δ 167.7 (CO), 157.7 (C),
151.9 (C), 151.4 (C), 140.7 (CH), 129.0 (CH), 127.8 (C), 123.4
(CH), 121.4 (C), 119.4 (C), 118.8 (CH), 118.6 (CH), 114.8 (CH),
55.2 (OCH3), 51.4 (OCH3) ppm; HRMS (ESI+): m/z calcd for
C17H17O5S [M + H]+: 333.0791, found: 333.0811.
Methyl 7-bromo-6-hydroxy-5-(3-methoxy-3-oxopropylthio)-2-
oxo-2H-chromene-3-carboxylate (8h): Reaction time: 2 min;
Yield: 0.170 g (68%) as yellow solid; mp: 170–171 oC; IR (KBr):
Methyl
(E)-3-(3,6-dihydroxy-2-(naphthalen-2-
ν
max 3248, 2946, 1740, 1697, 1561, 1366, 1161, 1044, 820, 667
ylthio)phenyl)acrylate (9d): Reaction time: 1 min; Yield: 0.150 g
1
cm–1; H NMR (500 MHz, CDCl3): 9.00 (s, 1H), 7.88 (s, 1H),
7.60 (s, 1H), 3.95 (s, 3H), 3.74 (s, 3H), 3.02 (t, J = 6.5 Hz, 2H),
2.60 (t, J = 7.0 Hz, 2H) ppm; 13CNMR (125 MHz, CDCl3): δ
172.1 (C), 163.5 (C), 155.8 (C), 152.7 (C), 149.1 (C), 146.6
(CH), 122.7 (CH), 120.0 (C), 118.9 (C), 117.3 (C), 116.9 (C),
52.0 (OCH3), 52.3 (OCH3), 33.0 (CH2), 31.3 (CH2) ppm; HRMS
o
(71%) as light brown solid; mp: 194–195 C; IR (KBr): νmax
3387, 2916, 1681, 1625, 1384, 1265, 1179, 1124, 815, 614 cm–1;
1H NMR (400 MHz, CDCl3 + DMSO-d6): δ 9.27 (s, 1H), 8.20 (d,
J = 16.0 Hz, 1H), 7.66 (d, J = 7.6 Hz, 1H), 7.60 (d, J = 8.8 Hz,
1H), 7.54 (d, J = 7.6 Hz, 1H|), 7.36–7.27 (m, 3H), 7.13 (d, J = 6.0
Hz, 1H), 7.03 (s, 1H), 7.00–6.97 (m, 1H), 6.91 (t, J = 8.8 Hz 1H),
3.62 (s, 3H) ppm; 13C NMR (100 MHz, CDCl3 + DMSO-d6): δ

10
168.1 (CO), 151.6 (C), 151.0 (C), 139.9 (CH), 138.9 (C), 133.3
(C), 131.3 (C), 128.4 (CH), 127.3 (CH), 126.7 (CH), 126.2 (CH),
125.3 (CH), 124.8 (CH), 124.5 (CH), 123.9 (C), 122.4 (CH),
119.6 (CH), 117.1 (CH), 51.1 (OCH3) ppm; HRMS (ESI+): m/z
calcd for C20H17O4S [M + H]+: 353.0842, found: 353.0861.
1. (a) Cano, R.; Ramón, D. J.; Yus, M. J. Org. Chem. 2011, 76,
ACCEPTED MANUSCRIPT
654. (b) Sach, N. W.; Richter, D. T.; Cripps, S.; Tran-Dubé, M.;
Zhu, H.; Huang, B.; Cui, J.; Sutton, S. C. Org. Lett. 2012, 14,
3886. (c) Mehta, V. P.; Punji, B. RSC Adv. 2013, 3, 1195.
2. (a) Tietze, L. F.; Beifuss, U. Angew. Chem., Int. Ed. Engl. 1993,
32, 131.(b) Tietze, L. F. Chem. Ind. (London) 1995, 12, 453.(c)
Tietze, L. F. Chem. Rev. 1996, 96, 115. (d) Tietze, L. F.; Lieb, M.
E. Curr. Opin. Chem. Biol. 1998, 2, 363. (e) Tietze, L. F.;
Brasche, G.; Gericke, K. In Domino Reactions in Organic
Synthesis; Wiley-VCH: Weinheim, Germany, 2006.
Methyl
(E)-3-(2-(4-bromophenylthio)-3,6-
dihydroxyphenyl)acrylate (9e): Reaction time: 1 min; Yield:
o
0.149 g (65%) as light brown solid; mp: 218–219 C; IR (KBr):
νmax 3328, 2919, 1690, 1628, 1433, 1338, 1264, 1190, 806, 642
1
cm–1; H NMR (400 MHz, DMSO-d6): δ 10.20 (s, 1H), 9.47 (s,
1H), 8.16 (d, J = 16.0 Hz, 1H), 7.41 (d, J = 8.4 Hz, 2H), 7.01–
6.88 (m, 5H), 3.65 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-
d6): 167.6 (CO), 152.1 (C), 151.5 (C), 140.0 (CH), 137.3 (C),
131.8 (CH), 127.8 (CH), 123.5 (C), 121.8 (CH), 119.5 (CH),
118.7 (CH), 117.8 (C), 116.6 (C), 51.4 (OCH3) ppm; HRMS
(ESI+): m/z calcd for C16H13BrO4SNa [M + Na]+: 402.9610,
found: 402.9533.
3. (a) Ilangovan, A.; Saravanakumar, S.; Malayappasamy, S. Org.
Lett. 2013, 15, 4968. (b) Walker, S. E.; Jordan-Hore, J. A.;
Johnson, D. G.; Macgregor, S. A.; Lee, A.-L. Angew. Chem. Int.
Ed. 2014, 53, 13876. (c) Chen, Y.-H.; Cheng, D.-J.; Zhang, J.;
Wang, Y.; Liu, X.-Y.; Tan, B. J. Am. Chem. Soc. 2015, 137,
15062. (b) Mori-Quiroz, L. M.; Clift, M. D. Org. Lett. 2016, 18,
3446. (c) Hosamani, B.; Ribeiro, M. F.; da Silva Júnior, E. N.;
Namboothiri, I. N. N. Org. Biomol. Chem. 2016, 14, 6913.
Methyl
(E)-3-(2-(4-chlorophenylthio)-3,6-
dihydroxyphenyl)acrylate (9f): Reaction time: 1 min; Yield:
0.131 g (65%) as light brown solid; mp: 216–217 C; IR (KBr):
4. (a) He, Z.; Liu, T.; Tao, H.; Wang, C.-J. Org. Lett. 2012, 14, 6230.
(b) Rojas-Martín, J.; Veguillas, M.; Ribagorda, M.; Carreňo, M. C.
Org. Lett. 2013, 15, 5686. (c) Löbermann, F.; Weisheit, L.;
Trauner, D. Org. Lett. 2013, 15, 4324. (d) Tran, M. Q.;
Ermolenko, L.; Retailleau, P.; Nguyen, T. B.; Al-Mourabit, A.
Org. Lett. 2014, 16, 920. (e) Fujii, Y.; Takehara, T.; Suzuki, T.;
Fujioka, H.; Shuto, S.; Arisawa, M. Adv. Synth. Catal. 2015, 357,
4055. (f) Mfuh, A. M.; Zhang, Y.; Stephens, D. E.; Vo, A. X. T.;
Arman, H. D.; Larionov, O. V. J. Am. Chem. Soc. 2015, 137,
8050. (g) Zhou, X.-L.; Wang, P.-S.; Zhang, D.-W.; Liu, P.; Wang,
C.-M.; Gong, L.-Z. Org. Lett. 2015, 17, 5120. (h) Guo, J.;
Chaithanya Kiran, I. N.; Reddy, R. S.; Gao, J.; Tang, M.; Liu, Y.;
He, Y. Org. Lett. 2016, 18, 2499. (i) Gelis, C.; Bekkaye, M.;
Lebée, C.; Blanchard, F.; Masson, G. Org. Lett. 2016, 18, 3422.
o
νmax 3412, 2950, 1690, 1624, 1432, 1358, 1193, 1080, 815, 620
1
cm–1; H NMR (400 MHz, DMSO-d6): δ 10.20 (s, 1H), 9.48 (s,
1H), 8.22 (d, J = 16.0 Hz, 1H), 7.27 (d, J =8.4 Hz, 2H), 7.03–
6.93 (m, 5H), 3.65 (s, 3H) ppm; 13C NMR (100 MHz, DMSO-
d6): δ 167.7 (CO), 152.2 (C), 151.6 (C), 140.2 (CH), 136.8 (C),
129.8 (C), 129.0 (CH), 127.6 (CH), 123.7 (C), 122.0 (CH), 119.6
(CH), 118.8 (CH), 117.0 (C), 51.4 (CH3) ppm; HRMS (ESI+):
m/z calcd for C16H14ClO4S [M + H]+: 337.0295, found: 337.0290.
Methyl
(E)-3-(2-(benzylthio)-3,6-dihydroxyphenyl)acrylate
(9g): Reaction time: 2 min; Yield: 0.129 g (68%) as light brown
o
solid; mp: 169–170 C; IR (KBr): νmax 3328, 2930, 1689, 1628,
1
1436 1338, 1264, 1190, 800, 647 cm–1; H NMR (400 MHz,
DMSO-d6): δ 9.82 (s, 1H), 9.25 (s, 1H), 8.15 (d, J = 16.0 Hz,
1H), 7.21–7.12 (m, 5H), 6.84–6.72 (m, 3H), 3.97 (s, 2H), 3.69 (s,
3H) ppm; 13C NMR (100 MHz, DMSO-d6): δ 167.8 (CO), 151.6
(C), 150.9 (C), 140.8 (CH), 138.0 (C), 128.8 (CH), 128.2 (CH),
126.9 (CH), 123.5 (C), 120.9 (CH), 120.7 (C), 117.7 (CH), 117.5
(CH), 51.3 (OCH3), 38.4 (CH2) ppm; HRMS (ESI+): m/z calcd
for C17H16O4S [M + Na]+: 339.0661, found: 339.0657.
5. (a) Suzuki, T.; Kubomura, K.; Takayama, H. Chem. Pharm. Bull.
1991, 39, 2164. (b) Canto, M.; March, P.; de Figueredo, M. J.;
Font Rodríguez, S.; Alvarez-Larena, A.; Piniella, J. F.
Tetrahedron: Asymmetry 2002, 13, 455. (c) Sankararaman, S.;
Srinivasan, M. Org. Biomol. Chem. 2003, 1, 2388. For examples,
see: (d) Furusaki, A.; Watanabe, T. Chem. Pharm. Bull. 1973, 21,
931. (e) Nagoaka, H.; Kishi, Y. Tetrahedron 1981, 37, 3873. (f)
Maddaford, S. P.; Andersen, N. G.; Cristofoli, W. A.; Keay, B. A.
J. Am. Chem. Soc. 1996, 118, 10766
Methyl
(E)-3-(2-(benzylthio)-3,6-dihydroxyphenyl)acrylate
(9h): Reaction time: 2 min; Yield: 0.131 g (70%) as brown solid;
o
mp: 130–131 C; IR (KBr): νmax 3389, 2919, 1684, 1585, 1384,
6. (a) Errante, G.; Motta, G. L.; Lagana, C.; Wittebolle, V.; Sarciron,
M.-É.; Barret, R. Eur J Med Chem 2006, 41, 773. (b) Lagorio, S.
H.; Bianchi, D. A.; Sutich, E. G.; Kaufman, T. S. Eur J Med
Chem. 2006; 41, 1333.
1
1269, 1171, 988, 829, 614 cm–1; H NMR (400 MHz, CDCl3 +
DMSO-d6): δ 9.04 (s, 1H), 8.23 (d, J = 16.0 Hz, 1H), 7.02 (d, J =
16.0 Hz, 1H), 6.89 (s, 1H), 6.82 (dd, J = 8.8, 21.6 Hz, 2H), 3.73
(s, 3H), 3.59 (s, 3H), 2.82 (t, J = 7.2 Hz, 2H), 2.42 (t, J = 6.8 Hz,
2H) ppm; 13C NMR (100 MHz, CDCl3 + DMSO-d6): δ 171.9
(CO), 168.5 (CO), 151.6 (C), 150.9 (C), 140.1 (CH), 123.5 (C),
122.5 (CH), 119.0 (CH), 118.7, 116.5 (CH), 51.75 (OCH3), 51.40
(OCH3), 33.4 (CH2), 30.8 (CH2) ppm; HRMS (ESI+): m/z calcd
for C14H17O6S [M +H]+: 313.0740, found: 313.0737.
7. (a) Yadav, J. S.; Swamy, T.; Reddy, B. V. S.; Rao, D. K., J. Mol.
Catal. A: Chem. 2007, 274, 116. (b) da Rocha, D. R.; de Souza, A.
C. G.; Resende, J. A. L. C.; Santos, W. C.; dos Santos, E. A.;
Pessoa, C.; de Moraes, M. O.; Costa-Lotufo, L. V.; Montenegro,
R. C.; Ferreira, V. F. Org. Biomol. Chem. 2011, 9, 4315.
8. Noland, W. E.; Kedrowski, B. L. J. Org. Chem. 2002, 67, 8366.
9. Tremblay, M. S.; Sames, D. Org. Lett. 2005, 7, 2417.
Acknowledgements
This work was supported by Council of Scientific and
Industrial Research (CSIR), New Delhi (research grant No.
02(0231)/15/EMR-II) for financial support and DST-FIST
program (HRMS facility), New Delhi and S.B. thanks CSIR for a
research fellowship. We thank Prof. U. P. Singh for collecting X-
ray crystallographic data.
10. Review: Medina, F. G.; Marrero, J. G.; Macías-Alonso, M.;
Gonzalez, M. C.; Córdova-Guerrero, I.; García, A. G. T.;
Osegueda-Roblesa, S. Nat. Prod. Rep. 2015, 32, 1472. (b)
Widelski, J.; Melliou, E.; Fokialakis, N.; Magiatis, P.; Glowniak,
K.; Chinou, I. J. Nat. Prod. 2005, 68, 1637.
11. (a) Murata, M.; Buchwald, S. L. Tetrahedron 2004, 60, 7397. (b)
Fernndez Rodrguez, M. A.; Shen, Q.-L.; Hartwig, J. F. J. Am.
Chem. Soc. 2006, 128, 2180. (c) Wang, L.; Zhou, W.-Y.; Chen,
Notes and references

11
S.-C.; He, M.-Y.; Chen, Q. Synlett 2011, 3041. d) Guan, P.; Cao,
ACCEPTED MANUSCRIPT
C.; Liu, Y.; Li, Y.; He, P.; Chen, Q.; Liu, G.; Shi, Y. Tetrahedron
Lett. 2012, 53, 5987. For review see: (e) Lee, C.-F.; Liu, Y.-C.;
Badsara, S. S. Chem. Asian J. 2014, 9, 706. (f) Kazemi, M.; Shiri,
L.; Kohzadi, H. Phosphorus, Sulfur, and Silicon 2015, 190, 978.
(g) Chauhan, P.; Mahajan, S.; Enders, D. Chem. Rev. 2014, 114,
8807.
12. Review: (a) Grover, J.; Jachak, S. M. RSC Adv. 2015, 5, 38892.
(b) Gaudino, E. C.; Tagliapietra, S.; Martina, K.; Palmisanob, G.;
Cravotto, G. RSC Adv. 2016, 6, 46394. (c) Cravotto, G.; Nano, G.
M.; Palmisano, G.; Pilati, T.; Tagliapietra, S. J. Heterocycl. Chem.
2001, 38, 965. (d) Bhat, M. A.; Al-Omar, M. A.; Siddiqui, N.
Med. Chem. Res. 2013, 22, 4455. (e) Nasr, T.; Bondock, S.;
Youns, M. Eur. J. Med. Chem. 2014, 76, 539.
13. (a) Pérez-Cruz, F.; Vazquez-Rodriguez, S.; Matos, M. J.; Herrera-
Morales, A.; Villamena, F. A.; Das, A.; Gopalakrishnan, B.; Olea-
Azar, C.; Santana, L.; Uriarte, E. J. Med. Chem. 2013, 56, 6136.
(b) Witaicenis, A.; Seito, L. N.; Chagas, A.; Da, S.; De Almeida
Junior, L. D.; Luchini, A. C.; Rodrigues-Orsi, P.; Cestari, S. H.; Di
Stasi, L. C. Phytomedicine 2014, 21, 240.
14. (a) Nielsen, S. F.; Nielsen, E. O.; Oslen, G. M.; Liljefors, T.;
Peters, D. J. Med. Chem. 2000, 43, 2217. (b) Liu, G.; Huth, J. R.;
Olejniczak, E. T.; Mendoza, R.; De Vries, P.; Leitza, S.; Reilly, E.
B.; Okasinski, G. F.; Fesik, S. W.; von Geldern, T. W. J. Med.
Chem. 2001, 44, 1202. (c) Parveen, S.; Khan, M. O. F.; Austin, S.
E.; Croft, S. L.; Yardly, V.; Rock, P.; Douglas, K. T. J. Med.
Chem. 2005, 48, 8087. (d) Beletskaya, I. P.; Ananikov, V. P.
Chem. Rev. 2011, 111, 1596.
15. Chen, Y.; Clouthier, C. M.; Tsao, K.; Strmiskova, M.; Lachance,
H.; Keillor, J. W. Angew. Chem. Int. Ed. 2014, 53, 13785.
16. (a) Peng, Y.-Y.; Wen, Y.; Qiu, X. G. Tetrahedron Lett. 2009, 50,
2405. (b) Rajesha, G.; Mahadevan, K. M.; Satyanarayan, N. D.;
Bhojya Naik, H. S. Phosphorus, Sulfur, and Silicon 2011, 186,
1733.(c) Paul, N.; Muthusubramanian, S. Med. Chem. Res. 2014,
23, 1612. (d) Tian, H.; Zhu, C.; Yanga, H.; Fu, H. Chem.
Commun. 2014, 50, 8875.
17. (a) Parumala, S. K. R.; Peddinti, R. K. Org. Lett. 2013, 15, 3546.
(b) Surasani, S. R.; Parumala, S. K. R.; Peddinti, R. K. Org.
Biomol. Chem. 2014, 12, 5656. (c) Sharma, S.; Naganaboina, R.
T.; Peddinti, R. K. RSC Adv. 2015, 5, 100060.
18. (a) Parumala, S. K. R.; Surasani, S. R.; Peddinti, R. K. New J.
Chem. 2014, 38, 5268. (b) Parumala, S. K. R.; Peddinti, R. K.
Green Chem. 2015, 17, 4068.
19. Jacob, P.; Callery, P. S.; Shulgin, A. T.; Castagnoli, N. J. Org.
Chem. 1976, 41, 3627.
20. (a) 4e: CCDC No. 1489675. (b) 5e: CCDC No. 1511658.
21. (a) Tundo, P.; Rossi, L.; Loris, A. J. Org. Chem. 2005, 70, 2219.
(b) Navarro, R.; Pérez, M.; Rodriguez, G.; Reinecke, H. Eur.
Polym. J., 2007, 43, 4516. (c) Azizi, N.; Khajeh-Amiri, A.;
Ghafuri, H.; Bolourtchian. M. Green Chem. Lett. Rev., 2009, 2,
43.
22. (a) Domingo, L. R.; Aurell, M. J. J. Org. Chem. 2002, 67, 959. (b)
Bultinck, P.; Carbó-Dorca, R. Langenaeker, W. J. Chem. Phys.
2003, 118, 4349. (c) Gayatri, G.; Sastry, N. J. Chem. Sci., 2005,
117, 573.