Pd-catalyzed cross-coupling study of bi-functional 3-bromo-4-trifloxycoumarins with triarylbismuth reagents

Article abstract of DOI:10.1016/j.tet.2015.05.060

Abstract The cross-coupling reactions of functionalized 3-bromo-4-trifloxycoumarins have been explored with threefold arylating triarylbismuth reagents. These palladium-catalyzed reactions afforded chemo-selective C-4 arylations with the facile formation of 3-bromo-4-arylcoumarins in good to high yields. Additionally, palladium-catalyzed arylations of functionalized 3-bromo-4-arylcoumarins also participated in the second arylation to give functionalized 3,4-diarylcoumarins in high yields.

Full text of DOI:10.1016/j.tet.2015.05.060

Tetrahedron 71 (2015) 5137e5147
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Tetrahedron
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Pd-catalyzed cross-coupling study of bi-functional 3-bromo-4-
trifloxycoumarins with triarylbismuth reagents
*
Maddali L.N. Rao , Abhijeet Kumar
Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The cross-coupling reactions of functionalized 3-bromo-4-trifloxycoumarins have been explored with
threefold arylating triarylbismuth reagents. These palladium-catalyzed reactions afforded chemo-
selective C-4 arylations with the facile formation of 3-bromo-4-arylcoumarins in good to high yields.
Additionally, palladium-catalyzed arylations of functionalized 3-bromo-4-arylcoumarins also partici-
pated in the second arylation to give functionalized 3,4-diarylcoumarins in high yields.
Ó 2015 Elsevier Ltd. All rights reserved.
Received 8 January 2015
Received in revised form 14 May 2015
Accepted 18 May 2015
Available online 22 May 2015
Keywords:
Pd-catalyzed
Cross-coupling
Triarylbismuth
3-Bromo-4-trifloxycoumarin
3-Bromo-4-arylcoumarin
3,4-Diarylcoumarin
1. Introduction
These efforts gave the opportunity for chemo-selective couplings of
3-bromo-4-trifloxycoumarins and their bis-coupling studies under
palladium-catalyzed conditions as outlined here.
Coumarin scaffolds are prevalent in various plant species1 and
are popular with a vast range of biological and medicinal proper-
ties.2 Arylated coumarins in particular, are precursors for various
biologically active drug molecular skeletons.3 The development of
new and viable synthetic methods for functionalized coumarins is
vital and of general interest, as this will augment studies using
coumarins for various medicinal and other applications.3,4 Transi-
tion metal catalyzed reactions have been extensively used for the
arylation of coumarin skeletons.5,6 Recently, we too have reported
the Pd-catalyzed synthesis of 4-arylcoumarins using triarylbismuth
reagents as threefold arylating agents.7,8 In continuation, we have
explored the novel reactivity of 3-bromo-4-trifloxycoumarin and
its other bromide derivatives (Fig. 1) with triarylbismuth reagents.
2. Results and discussion
To start this coupling study, the required 3-halo-4-
trifloxycoumarins have been prepared from 4-hydroxycoumarins
as given in Scheme 1.6a,9
O
O
X
O
O
X
O
O
Conditions B
Conditions A
R
R
R
Step 2
(56-68%)
Step 1
(75-88%)
OTf
OH
OH
(X = Br or Cl)
1a-1e (X = Br)
1f (X = Cl)
1a, R = H; 1b, R = 6-Ph; 1c, R = 7,8-Benzofused;
1d, R = 6-Br; 1e, R = 6,8-Dibromo; 1f, R = H
Conditions A: NBS or NCS (1.05 equiv), NH4OAc (0.1 equiv), MeCN, rt, 3-10 h
Conditions B: Tf2O (1.5 equiv), Et3N (1.2 equiv), CH2Cl2, 0 oC - rt, 10 h
Scheme 1. Synthesis of 3-halo-4-trifloxycoumarins.
It was of interest to explore the competitive coupling reactivity
of bi-functional 3-bromo-4-trifloxycoumarins in the context of
facile couplings witnessed vide supra using 4-bromo, 4-chloro and
4-trifloxycoumarin derivatives and triarylbismuth reagents. To
understand the bi-functional coupling reactivity of 3-bromo-4-
trifloxycoumarin, it was tested with tri(p-anisyl)bismuth as
Fig. 1. Coumarin skeletons with reactive functionality.
* Corresponding author. Tel./fax: þ91 512 2597532; e-mail address: maddali@
iitk.ac.in (M.L.N. Rao).
http://dx.doi.org/10.1016/j.tet.2015.05.060
0040-4020/Ó 2015 Elsevier Ltd. All rights reserved.

5138
M.L.N. Rao, A. Kumar / Tetrahedron 71 (2015) 5137e5147
summarized in Table 1. The reactivity of 3.3 equiv of 3-bromo-4-
trifloxycoumarin was initially studied with 1 equiv of tri(p-anisyl)
bismuth using PdCl2(PPh3)2 (0.09 equiv), K3PO4 (1 equiv) in DMA at
90 ꢀC for 2 h and this testing provided selective coupling at triflate
terminus to give chemo-selectively coupled 3-bromo-4-(4-
methoxyphenyl)-2H-chromen-2-one (2.1) in 50% yield (Entry 1,
Table 1). It was further tested with bases involving KOAc, Na2CO3
and NaHCO3 to check their utility to improve the yield (Entries 2e4,
Table 1). From this, the reaction with NaHCO3 showed a marginal
improvement up to 58% yield. Importantly, we have observed the
hydrolysis of triflate terminus and the corresponding 4-
hydroxycoumarin was observed in minor amount at the end of
the reaction. To circumvent this problem, the coupling was tested
with 4 equiv of 1a and this showed the improvement to afford 66%
yield (Entry 5, Table 1).
from organic electrophile and threefold coupling of triarylbismuths
to deliver high yields. In general, the couplings of 1a with elec-
tronically different triarylbismuths proved to be more efficient with
arylations selectively at 4-position. This reactivity gave the re-
spective 3-bromo-4-arylcoumarins (2.1e2.10) in 63e88% yields
(Entries 1e10, Table 2). In particular, the coupling reaction carried
out with 4-CF3 substituted BiPh3 reacted somewhat poorly and
gave 2.11 in 36% yield (Entry 11, Table 2). The broadness of the
established protocol was further tested with electronically different
3-bromo-6-phenyl-4-trifloxycoumarin (1b), 7,8-benzofused 3-
bromo-4-trifloxycoumarin (1c), 3,6-dibromo-4-trifloxycoumarin
(1d) and 3,6,8-tribromo-4-trifloxycoumarin (1e) substrates. It was
planned to explore the respective chemo-selective coupling re-
activity of these substrates with triarylbismuth reagents. Under the
established conditions, the reactions of 1b and 1c gave coupling
products (2.12e2.22) in 60e86% yields (Entries 12e22, Table 2). The
reactivity tested with 1d and 1e with additional bromo sub-
stitutions provided the selective couplings at C-4 position with the
formation of 3,6-dibromo-4-arylcoumarins (2.23e2.26) and 3,6,8-
tribromo-4-arylcoumarins (2.27e2.29) in 61e74% yields (Entries
23e29, Table 2). One of these products, 3,6-dibromo-4-p-tolyl-2H-
chromen-2-one (2.23) was crystallized out and found to be suitable
for single X-ray crystal analysis (Fig. 2). This further established
unambiguously the selective arylation at 4-position. Finally, the
formation of diverse 3-bromo-4-arylcoumarins in good to excellent
yields was witnessed from chemo-selective arylation of 3-bromo-
4-trifloxycoumarins with the optimized conditions. The chemo-
selective couplings leaving 3-bromo group intact allows further
functionalizations.4,10
Having successfully established chemo-selective couplings at 4-
position, it was of interest to further functionalize 3-bromo-4-
arylcoumarin with triarylbismuth reagents. To check this feasibil-
ity, a brief screening was carried out using earlier established
conditions (Scheme 2).
Under the conditions tested, the desired arylation at 3-bromo
position took place moderately with the formation of 3,4-bis(4-
methoxyphenyl)-2H-chromen-2-one (3.1) in 53% yield. The ap-
plied conditions with 4 h duration furnished 60% yield, while the
heating at 110 ꢀC for 2 h afforded 73% yield. The bis-coupling yield
was further improved to 80% at 110 ꢀC, 4 h condition. It was satis-
fying to realize that the optimized protocol established for chemo-
selective couplings was found to be appropriate for second aryla-
tion with slight modification in reaction temperature and time to
furnish high yield.
Table 1
Screening conditionsa,b
O
O
O
O
Catalyst (0.09 equiv)
+
Bi
OMe
Br
Br
base, solvent
temp. (oC), time (h)
3
OTf
2.1
(1 equiv)
1a
(4 equiv)
OMe
(3 equiv)
Entry
Catalyst
Base (equiv)
Solvent
Yield (%)
1
2
3
4
5
6
7
8
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
PdCl2(PPh3)2
Pd(PPh3)4
K3PO4 (1)
KOAc (1)
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMF
NMP
DMA
DMA
DMA
DMA
DMA
DMA
DMA
DMA
50c
45c
56c
58c
66
67
52
77
58
Na2CO3 (1)
NaHCO3 (1)
NaHCO3 (1)
NaHCO3 (1)
NaHCO3 (1)
NaHCO3 (1)
NaHCO3 (1)
NaHCO3 (1)
NaHCO3 (2)
NaHCO3 (0.5)
NaHCO3 (1)
NaHCO3 (1)
NaHCO3 (1)
NaHCO3 (1)
d
Pd(OAc)2/4PPh3
Pd(OAc)2(Cy2NH)2
Pd(OAc)2(Cy2NH)2
Pd(OAc)2(Cy2NH)2
Pd(OAc)2(Cy2NH)2
Pd(OAc)2(Cy2NH)2
Pd(OAc)2(Cy2NH)2
Pd(OAc)2(Cy2NH)2
Pd(OAc)2(Cy2NH)2
Pd(OAc)2(Cy2NH)2
Pd(OAc)2(Cy2NH)2
d
9
10
11
12
13
14
15
16
17
18
69
52
60
62d
65e
58f
67g
56
NaHCO3 (1)
d
a
Reaction conditions: 1a (0.5 mmol, 4 equiv), tri(p-anisyl)bismuth (0.125 mmol,
1 equiv), Pd(OAc)2(Cy2NH)2 (0.011 mmol, 0.09 equiv), base (0.125 mmol, 1 equiv),
DMA (3 mL), 2 h, 90 ꢀC.
b
Isolated yields based on three aryl coupling from BiAr3; bianisyl formed in
The 3-bromo arylation was carried out with different 3-bromo-
4-arylcoumarins and BiAr3 reagents. The effective second aryla-
tions were witnessed with the formation of 3,4-diarylcoumarins
(3.1e3.12) (Entries 1e12, Table 3) in 61e80% yields. These couplings
carried with different BiAr3 reagents furnished both symmetrically
and unsymmetrically substituted 3,4-diarylcoumarins in good to
high yields.
5e22% amounts.
c
With 1a in 3.3 equiv (0.412 mmol).
d
At 60 ꢀC.
e
At 100 ꢀC.
With1 h.
f
g
With 0.05 equiv catalyst.
Additional check with different catalyst precursors (Entries 6e8,
Table 1) revealed the better performance with Pd(OAc)2(Cy2NH)2
and in this case 77% yield was obtained (Entry 8, Table 1). Further
study in DMF or NMP did not improve the yield (Entries 9 and 10,
Table 1). Further scrutiny with base, temperature, catalyst and time
(Entries 11e18, Table 1) gave additional clarity of the overall re-
quirement for better coupling reactivity. This made us to consider
the combination with Pd(OAc)2(Cy2NH)2 (0.09 equiv) and NaHCO3
(1 equiv) in DMA at 90 ꢀC for 2 h as the most effective (Entry 8, Table
1) to achieve high cross-coupling yield with chemo-selective
coupling.
In addition, the bis-arylated 3,4-bis (4-methoxyphenyl)-2H-
chromen-2-one (3.1) was measured by single X-ray crystal analysis
(Fig. 3). The optimized conditions thus allowed the synthesis of
various 3,4-diarylcoumarins in a facile manner. The practical utility
of these products is high as some of the hybrid derivatives of 3,4-
diarylcoumarins have been reported to exhibit DNA-binding and
anti-proliferative activities.11 Further, some diarylated coumarin
analogues were studied as estrogen receptor modulators.12 The
corresponding 3,4-diarylchromanes have been explored as estro-
gen agonists.13
In continuation, the synthesis of symmetrically substituted 3,4-
diarylcoumarin (3.1) was attempted in one pot operation (Scheme
3). However, under the conditions employed, the exclusive aryla-
tion at C-4 position was obtained with the formation of 2.1 in 79%
yield. The corresponding bis-arylated product 3.1 was not formed
The generality of these couplings was further investigated with
divergent 3-bromo-4-trifloxycoumarins and triarylbismuths under
established coupling conditions (Table 2). This evaluation demon-
strated excellent consistency in terms of chemo-selective coupling

M.L.N. Rao, A. Kumar / Tetrahedron 71 (2015) 5137e5147
5139
Table 2
Pd-catalyzed chemo-selective couplings with 3-bromo-4-trifloxycoumarins and BiAr3 reagentsa,b
O
O
O
O
Ar
Ar
Pd(OAc)2(Cy2NH)2 (0.09 equiv)
R
Bi
Ar
R
+
Br
Br
NaHCO3 (1 equiv), DMA
90 oC, 2 h
OTf
(4 equiv)
Ar
(1 equiv)
(3 equiv)
3-Bromo-4-aryl
coumarin
3-Bromo-4-aryl
coumarin
3-Bromo-4-trifloxy
coumarin
3-Bromo-4-trifloxy
coumarin
Ar3Bi
Entry
16
Entry
1
Ar3Bi
Yield (%)
79
Yield (%)
77
O
O
Br
Br
O
O
O
O
O
O
OiPr
Bi
OMe
Bi
Bi
Bi
OiPr
OMe
Br
Br
Ph
Ph
OTf
OTf
3
3
2.16
2.1
2.2
2.3
1a
Ph
1b
Br
O
O
O
O
Br
O
O
O
O
F
F
3
Br
2
60
Bi
Bi
Bi
Bi
17
Br
84
OTf
OTf
3
2.17
1b
1a
Ph
Br
Br
O
O
O
Br
O
O
O
Me
2.18
O
Me
Me
O
Me
Br
3
4
Br
72
62
88
64
18
19
3
OTf
OTf
3
1c
1a
O
O
O
O
OMe
Br
Br
OMe
O
O
O
O
Bi
Br
Br
OTf
3
3
OTf
1a
2.4
2.19
2.20
1c
Br
O
OMe
O
O
OMe
O
O
O
O
OMe
O
Bi
Bi
OMe
OMe
5
6
7
OMe
76
73
20
21
70
82
Br
Br
3
OTf
OTf
3
2.5
2.6
2.7
1a
1c
O
Br
O
O
O
O
Br
O
O
OEt
2.21
O
OEt
F
OEt
Br
Bi
Bi
Bi
OEt
OTf
Br
3
3
OTf
1a
1c
O
O
Br
O
O
O
Br
Br
O
OiPr
2.22
F
O
O
Br
64
82
63
Bi
Bi
OiPr
22
23
24
86
72
OTf
3
Br
3
1a
OTf
O
Br
1c
O
O
O
O
OiPr
OiPr
O
O
O
8
9
Br
Me
2.23
3
Me
OTf
Br
Br
Br
2.8
2.9
3
1a
OTf
1d
Br
Br
O
O
Br
Br
O
O
Bi
Bi
Cl
3
Cl
O
O
Br
O
O
OTf
OMe
2.24
Bi
Bi
OMe
OEt
1a
Br
71
OTf
3
O
O
1d
O
O
Br
Br
OnBu
OnBu
10
74
Br
O
O
3
OTf
O
O
2.10
2.11
OEt
2.25
1a
74
72
25
26
Br
Br
Br
O
O
Br
Br
O
O
OTf
1d
3
CF3
11
12
Bi
CF3
3
Br
Br
Br
36
78
OTf
1a
O
O
O
O
O
O
O
O
OiPr
2.26
Bi
Bi
OiPr
Br
OMe
OTf
Bi
Bi
OMe
Br
Ph
3
3
1d
OTf
3
Br
1b
2.12
2.13
2.14
Ph
Br
O
Br
Br
O
O
O
O
O
O
OMe
2.27
O
Me
OMe
13
61
67
27
28
29
Me
74
81
Br
Ph
3
Br
Br
Br
OTf
OTf
Br
Br
1b
1e
Ph
Br
Br
Br
O
O
O
O
O
O
O
OiPr
2.28
O
Bi
Bi
OiPr
Me
OEt
Bi
Bi
OEt
Br
Ph
Ph
14
15
Br
Br
Br
Br
OTf
1b
3
3
OTf
1e
Br
Br
Ph
Br
O
O
O
O
Me
O
O
O
O
Me
Me
2.29
Br
70
68
Br
OTf
OTf
Br
3
3
1b
1e
2.15
Br
Ph
a Reaction conditions: 1a-1e (0.5 mmol, 4 equiv), Ar3Bi ( 0.125 mmol, 1 equiv), Pd(OAc)2(Cy2NH)2 (0.011 mmol, 0.09 equiv), NaHCO3 (0.125 mmol, 1 equiv),
and DMA (3 mL), 90 oC, 2 h. b Isolated yields based on threefold coupling from Ar3Bi reagents; biaryls formed in 5-16% amounts.

5140
M.L.N. Rao, A. Kumar / Tetrahedron 71 (2015) 5137e5147
triarylbismuths as threefold arylating partners under palladium
coupling conditions. In these couplings, 3-bromo-4-
trifloxycoumarins have selectively afforded C-4 arylations in good
to high yields. Further, a facile approach for the synthesis of 3,4-
diarylcoumarins was demonstrated involving 3-bromo-4-
arylcoumarins and bismuth reagents. The work described sig-
nifies the facile and robust nature of our methodology with triar-
ylbismuths in structural elaborations leading to mono-, di- and
triarylated coumarins. These methods embedded with high prac-
tical and synthetic scope are expected to find further applications in
organic synthesis.
Fig. 2. Crystal structure of 2.23 (CCDC No.1059353).
4. Experimental section
4.1. General remarks
O
O
O
O
Pd(OAc)2(Cy2NH)2
(0.09 equiv)
Br
+
Bi
OMe
NaHCO3 (1 equiv), DMA
temp., time
3
OMe
3.1
2.1
The cross-coupling reactions under palladium conditions have
been performed under nitrogen atmosphere in oven dried Schlenk
tubes. Literature procedures have been adopted for the synthesis of
3-bromo-4-trifloxycoumarins (1ae1e)6a,9 and triarylbismuth
compounds.14 NMR spectra were recorded on JEOL-500 MHz (ECX
500) and JEOL-400 MHz (JNM-ECS) spectrometers. WATERS-Q-Tof
Premier-HAB213 and WATERS GCT Premier-CAB155 instruments
were used to measure HRMS spectra. Bruker Vector 22 FTIR spec-
trometer were used to measure IR spectra. Purification of the crude
products was carried out using silica gel column chromatography
with hexane and ethyl acetate as eluent. Standard drying methods
have been applied for purification of solvents.
(1 equiv)
OMe
(3 equiv)
OMe
(3 equiv)
(a) 90 oC, 2 h, 53%
(b) 90 oC, 4 h, 60%
(c) 110 oC, 2 h, 73%
(d) 110 oC, 4 h, 80%
Conditions:
Scheme 2. Screening for arylation at 3-bromo position.
in this reaction. From this, it was clear that further modification of
the coupling conditions is necessary to achieve the one-pot bis-
arylation using 3-bromo-4-trifloxycoumarin.
We also attempted the synthesis of triarylated coumarin by
exploiting the differential reactivity with different bromide sub-
stitutions. For example, the sequential arylation of 3,6-dibromo-4-
(4-methoxyphenyl)-2H-chromen-2-one (2.24) was attempted
(Scheme 4).
4.2. Representative procedures for compounds 1ae1f
Initially, the arylation at arylbromide terminus was carried out
with tri(p-isopropoxyphenyl)bismuth using PdCl2(PPh3)2 with
KOAc in DMFat 90 ꢀC to afford 4.1 in 60% yield (Conditions A, Scheme
4).7 In the next step, it was further cross-coupled with tri(p-ethox-
yphenyl)bismuth under the conditions established (Conditions B,
Scheme 4). This endeavor furnished 3,4,6-triarylated coumarin 4.2
in 65% yield. The synthesis of triarylated coumarin under different
conditions demonstrates the selective and practicable nature of our
cross-coupling methodology under different reaction conditions.
At this stage we were curious to test the coupling reactivity of 3-
chloro-4-trifloxycoumarin as given in Scheme 5. Under our estab-
lished conditions, this reaction afforded 5.1 in 39% yield as chemo-
selective coupling product. Further attempt to convert 5.1 to the
corresponding 3,4-diarylcoumarin (3.1) under the conditions
employed for second arylation (Table 3) did not afford the product.
It is to be highlighted that the coupling reactions carried out in
the present study with tiarylbismuth reagents has threefold cou-
pling advantage in comparison to similar couplings reported with
arylboronic acids6a for the functionalization of 3-bromo-4-
trifloxycoumarin under palladium coupling conditions. In cou-
plings with arylboronic acids two different catalytic protocols were
needed to achieve bis-arylations of 3-bromo-4-trifloxycoumarin to
obtain 3,4-diarylcoumarin via 3-bromo-4-arylcoumarin. However,
in our case it was essentially one protocol conditions but with
simpler modification of reaction temperature adopted with estab-
lished protocol conditions for the second arylation step. Overall, the
reactivity unleashed with triarylbismuth reagents showed broad
applicability under the established coupling conditions.
4.2.1. Preparation of 3-bromo-4-hydroxy-2H-chromen-2-one
(step1).9 Bromination of 4-hydroxycoumarin (5 g, 30.8 mmol)
was carried out in acetonitrile (100 mL) with the addition of N-
bromosuccinimide (5.7 g, 32.34 mmol) followed by ammonium
acetate (0.237 g, 3.08 mmol). The reaction mixture was stirred at rt
for 3 h. After the reaction time, organic solvent was evaporated and
the crude was treated with ethyl acetate and water mixture (50 mL,
1:1). The organic layer was extracted with ethyl acetate (3ꢁ20 mL),
treated with brine, dried over anhydrous MgSO4 and concentrated
under reduced pressure. The crude product was purified by crys-
tallization to obtain 3-bromo-4-hydroxycoumarin as light yellow
solid (6.5 g, 88%). It was used directly in the next step.
4.2.2. Preparation of 3-bromo-2-oxo-2H-chromen-4-yl trifluoro-
methanesulfonate, 1a (step 2).6a A dried two-neck round bottom
flask was charged with 3-bromo-4-hydroxycoumarin (5 g,
20.7 mmol) and dry dichloromethane (100 mL). The mixture was
cooled to ice bath temperature. Then triethylamine (3.4 mL,
24.8 mmol) was added and stirred for 5 min followed by triflic
anhydride (5.2 mL, 31 mmol) slowly. The resultant mixture was
allowed to stir at rt for 10 h. After reaction time, it was quenched
with water and extracted with dichloromethane (3ꢁ20 mL) and
dried over anhydrous MgSO4 and concentrated. It was purified by
silica gel column chromatography (2% EtOAc/petroleum ether) to
obtain 1a as white solid (4.8 g, 62%).
4.2.3. 3-Bromo-2-oxo-2H-chromen-4-yl trifluoromethanesulfo-nate
(1a).6a White solid (62%); mp 100e102 ꢀC, Rf (10% ethyl acetate
in hexane) 0.74; IR (KBr, cmꢂ1): 1746, 1609, 1564, 1429, 1327, 1246,
1210, 1139, 1051, 993, 895, 791, 758, 745, 653, 632, 587; dH NMR
(500 MHz, CDCl3): 7.76e7.70 (m, 2H, AreH), 7.46e7.43 (m, 2H,
AreH); dC NMR (100 MHz, CDCl3): 156.94, 154.79, 151.57, 133.98,
125.61, 122.88, 118.36 (q, J¼322.85 Hz), 117.28, 115.20, 107.25; ESI
3. Conclusion
We have disclosed an efficient protocol for the chemo-selective
synthesis of
a
library of 3-bromo-4-arylcoumarins using

M.L.N. Rao, A. Kumar / Tetrahedron 71 (2015) 5137e5147
5141
Table 3
Synthesis of 3,4-diarylated coumarinsa,b
O
O
O
O
O
O
Bi
OiPr
3
Bi
OEt
3
Br
Br
Br
iPrO
4.2 (65%)
OEt
iPrO
4.1 (60%)
Conditions A
Conditions B
OMe
OMe
OMe
2.24
Conditions A: Compound 2.24 (0.412 mmol, 3.3 equiv), tri(p-isopropoxyphenyl)bismuth (0.125 mmol, 1 equiv),
PdCl2(PPh3)2 (0.011 mmol, 0.09 equiv), KOAc (0.5 mmol, 4 equiv), DMA (3 mL), 90 oC, 8 h
Conditions B: Compound 4.1 (0.206 mmol, 3.3 equiv), tri(p-ethoxyphenyl)bismuth (0.062 mmol, 1 equiv),
Pd(OAc)2(Cy2NH)2 (0.005 mmol, 0.09 equiv), NaHCO3 (0.062 mmol, 1 equiv), DMA (3 mL),
oC, 4 h
110
Scheme 4. Synthesis of 3,4,6-triarylated coumarin.
Fig. 3. Crystal structure of 3.1 (CCDC No. 1059354).
O
O
O
O
Pd(OAc)2(Cy2NH)2
(0.09 equiv)
O
O
Cl
Pd(OAc)2(Cy2NH)2
(0.09 equiv)
O
O
O
O
Br
+
+
Bi
OMe
Bi
+
OMe
Br
3
OMe
Cl
3
NaHCO3 (1.0 equiv)
DMA, 90 oC, 2 h
NaHCO3 (1.0 equiv)
DMA, 90 oC, 2 h
OTf
OTf
1a
OMe
(1 equiv)
OMe
3.1 (Not formed)
OMe
(1 equiv)
(2 equiv)
(4 equiv)
5.1 (39%)
2.1 (79%)
Scheme 5. Cross-coupling with 3-chloro-4-trifloxycoumarin.
Scheme 3. Attempted one-step bis-arylations.

5142
M.L.N. Rao, A. Kumar / Tetrahedron 71 (2015) 5137e5147
(HRMS) (m/z) calcd for C10H8BrF3NO5S [MþNH4]þ 389.9259, found:
(1% EtOAc/petroleum ether) to obtain compound 2.2 as white solid
(0.095 g, 84%). For the yield calculation 0.375 mmol of the product
was considered as 100% yield. It was identified by spectroscopic
analysis and in comparison with the known data.6a
389.9251.
4.2.4. 3-Bromo-2-oxo-6-phenyl-2H-chromen-4 trifluoromethane-
sulfonate (1b). Light yellow solid (65%); mp 118e120 ꢀC, Rf (10%
ethyl acetate in hexane) 0.63; IR (KBr, cmꢂ1): 1753, 1618, 1572, 1413,
1228, 1126, 760; dH NMR (500 MHz, CDCl3): 7.94e7.91 (m, 2H,
AreH), 7.58 (d, J¼7.45 Hz, 2H, AreH), 7.53e7.49 (m, 3H, AreH), 7.43
(t, J¼7.45 Hz, 1H); dC NMR (125 MHz, CDCl3): 156.97, 154.81, 150.83,
139.09, 138.41, 132.85, 129.28, 128.44, 127.02, 120.92, 118.39 (q,
J¼319.16 Hz), 117.68, 115.44, 107.61; ESI (HRMS) (m/z) calcd for
4.3.2. Synthesis of 3,4-bis(4-methoxyphenyl)-2H-chromen-2-one
(3.1) (Table 3). The cross-coupling procedure given in 4.3.1 was
adopted using conditions: 3-Bromo-4-(4-methoxyphenyl)-2H-
chromen-2-one (0.375 mmol, 0.124 g), tri(p-anisyl)bismuth
(0.125 mmol, 0.066 g), NaHCO3 (0.125 mmol, 0.010 g), Pd(OAc)2(-
Cy2NH)2 (0.011 mmol, 0.006 g), DMA (3 mL), 110 ꢀC, 4 h. The crude
product was subjected to silica gel column chromatography (10%
EtOAc/petroleum ether) to afford compound 3.1 as white solid
(0.108 g, 80%).
C
16H12BrF3NO5S [MþNH4]þ 465.9572, found: 465.9575.
4.2.5. 3-Bromo-2-oxo-2H-benzo[h]chromen-4-yl trifluorometh-
anesulfonate (1c). Light yellow solid (56%); mp 132e134 ꢀC, Rf
(10% ethyl acetate in hexane) 0.62; IR (KBr, cmꢂ1): 1741, 1596, 1428,
1232, 1135, 1086, 994, 913, 816, 754, 593; dH NMR (500 MHz,
CDCl3): 8.53 (d, J¼8.05 Hz, 1H, AreH), 7.92 (d, J¼8.0 Hz, 1H, AreH),
7.81 (d, J¼9.15 Hz, 1H, AreH), 7.76e7.65 (m, 3H, AreH); dC NMR
(100 MHz, CDCl3): 157.24, 155.68, 149.67, 135.40, 130.21, 128.29,
128.08, 125.85, 122.56, 122.33, 118.40 (q, J¼322.85 Hz), 117.42,
110.71, 106.03; ESI (HRMS) (m/z) calcd for C14H7BrF3NO5S [MþH]þ
422.9150, found: 422.9141.
4.3.3. Synthesis of 3-bromo-6-(4-isopropoxyphenyl)-4-(4-
methoxyphenyl)-2H-chromen-2one (4.1) (Scheme 4). The cross-
coupling procedure given in 4.3.1 was adopted using conditions:
Compound 2.24 (0.412 mmol, 0.168 g), tri(p-isopropoxyphenyl)
bismuth (0.125 mmol, 0.076 g), KOAc (0.5 mmol, 0.049 g),
PdCl2(PPh3)2 (0.011 mmol, 0.007 g), DMA (3 mL), 90 ꢀC, 8 h. The
crude product was purified on silica gel by column chromatography
(8% EtOAc/petroleum ether) to afford compound 4.1 as white solid
(0.105 g, 60%).
4.2.6. .43,6-Dibromo-2-oxo-2H-chromen-4-yl trifluorometha-
nesulfonate (1d). White solid (68%); mp 136e138 ꢀC, Rf (10% ethyl
acetate in hexane) 0.64; IR (KBr, cmꢂ1): 1739,1610,1556,1419,1449,
1225, 1130, 1053, 1001, 901, 823, 794, 788, 756, 727, 633, 591; dH
NMR (500 MHz, CDCl3): 7.84 (d, J¼2.3 Hz, 1H, AreH), 7.80 (dd,
J¼2.02, 8.87 Hz, 1H, AreH), 7.34 (d, J¼8.6 Hz, 1H, AreH); dC NMR
(100 MHz, CDCl3): 156.30, 153.43, 150.34, 136.80, 125.31, 118.97,
118.54, 118.34 (q, J¼323.17 Hz), 116.66, 108.77; ESI (HRMS) (m/z)
calcd for C10H7Br2F3NO5S [MþNH4]þ 469.8343, found: 469.8336.
4.3.4. Synthesis of 3-(4-ethoxyphenyl)-6-(4-isopropoxyphenyl)-4-(4-
methoxy-phenyl)-2H-chromen-2-one (4.2) (Scheme 4). The cross-
coupling procedure given in 4.3.1 was adopted using conditions:
Compound 4.1 (0.206 mmol, 0.095 g), tri(p-ethoxyphenyl)bismuth
(0.062 mmol, 0.035 g), NaHCO3 (0.062 mmol, 0.005 g), Pd(OAc)2(-
Cy2NH)2 (0.005 mmol, 0.003 g), DMA (3 mL), 110 ꢀC, 4 h. The crude
product was purified by silica gel by column chromatography (10%
EtOAc/petroleum ether) to afford compound 4.2 as white solid
(0.061 g, 65%).
4.2.7. 3,6,8-Tribromo-2-oxo-2H-chromen-4-yl trifluorometha-
nesulfonate (1e). White solid (64%); mp 142e144 ꢀC, Rf (10% ethyl
acetate in hexane) 0.80; IR (KBr, cmꢂ1): 1735,1607,1548,1439,1415,
1298, 1224, 1139, 1071, 1000, 909, 866, 802, 755, 609, 600, 498; dH
NMR (500 MHz, CDCl3): 8.04 (d, J¼1.7 Hz, 1H, AreH), 7.79 (d,
J¼2.25 Hz, 1H, AreH); dC NMR (100 MHz, CDCl3): 155.30, 152.91,
147.48, 139.55, 124.52, 118.44, 118.32 (q, J¼323.17 Hz), 117.50, 112.15,
109.53; ESI (HRMS) (m/z) calcd for C10H6Br3F3NO5S [MþNH4]þ
547.7448, found: 547.7435.
The characterization data for all the cross-coupled products are
given below.
4.3.5. 3-Bromo-4-(4-methoxyphenyl)-2H-chromen-2-one
(2.1).6a Pale yellow solid (0.096 g, 77%); mp 170e172 ꢀC, Rf (10%
ethyl acetate in hexane) 0.31; IR (KBr, cmꢂ1): 1731, 1605, 1507, 1450,
1297, 1273, 1251, 1171, 1034, 983, 810, 755, 626, 587; dH NMR
(500 MHz, CDCl3): 7.55 (t, J¼6.72 Hz, 1H, AreH), 7.40 (d, J¼8.55 Hz,
1H, AreH), 7.25 (d, J¼9.15 Hz, 2H, AreH), 7.20e7.15 (m, 2H, AreH),
7.07 (d, J¼8.55 Hz, 2H, AreH), 3.90 (s, 3H); dC NMR (125 MHz,
CDCl3): 160.23, 157.49, 154.49, 152.39, 131.94, 129.72, 127.69, 127.25,
124.62, 120.50, 116.79, 114.16, 112.74, 55.36; ESI (HRMS) (m/z) calcd
for C16H12BrO3 [MþH]þ 330.9970, found: 330.9974.
4.2.8. 3-Chloro-2-oxo-2H-chromen-4-yl trifluoromethane-sulfonate
(1f). White solid (64%); mp 88e90 ꢀC, Rf (10% ethyl acetate in
hexane) 0.74; IR (KBr, cmꢂ1): 1727, 1604, 1566, 1427, 1347, 1281,
1229, 1133, 1056, 1013, 896, 761, 747, 594; dH NMR (400 MHz,
CDCl3): 7.74e7.68 (m, 2H, AreH), 7.48e7.44 (m, 2H, AreH); dC NMR
(100 MHz, CDCl3): 156.74, 152.26, 150.92, 133.81, 125.71, 122.84,
118.36 (q, J¼322.53 Hz), 117.29, 116.23, 114.98; EI (HRMS) (m/z)
calcd for C10H4ClF3O5S [M]þ 327.9420, found: 327.9424.
4.3.6. 3-Bromo-4-phenyl-2H-chromen-2-one (2.2).6a Light yellow
solid (0.095 g, 84%); mp 140e142 ꢀC, Rf (10% ethyl acetate in hex-
ane) 0.52; IR (KBr, cmꢂ1): 1728, 1592, 1552, 1446, 1272, 1033, 991,
753, 697, 604; dH NMR (500 MHz, CDCl3): 7.58e7.52 (m, 4H, AreH),
7.41 (d, J¼8.3 Hz, 1H, AreH), 7.31e7.29 (m, 2H, AreH), 7.20e7.17 (m,
1H, AreH), 7.08 (dd, J¼1.42, 8.02 Hz, 1H, AreH); dC NMR (125 MHz,
CDCl3): 157.36, 154.63, 152.47, 135.28, 132.03, 129.35, 128.86, 128.07,
127.61, 124.70, 120.33, 116.83, 112.64; ESI (HRMS) (m/z) calcd for
4.3. Representative cross-coupling procedures
4.3.1. Synthesis of 3-bromo-4-phenyl-2H-chromen-2-one (2.2) (Table
2). A hot-oven dried Schlenk tube was charged with 3-bromo-4-
trifloxycoumarin (0.5 mmol, 0.186 g), BiPh3 (0.125 mmol,
0.055 g), NaHCO3 (0.125 mmol, 0.010 g), Pd(OAc)2(Cy2NH)2
(0.011 mmol, 0.006 g) and DMA (3 mL) under nitrogen atmosphere.
The reaction mixture was stirred in an oil bath at 90 ꢀC for 2 h. At
the end of the reaction time, the contents were brought to rt,
quenched with water (10 mL) and extracted with ethyl acetate
(3ꢁ15 mL). The organic extract was treated with brine, dried using
MgSO4 and the solvent was removed under reduced pressure. The
crude product was purified on silica gel column chromatography
C
15H10BrO2 [MþH]þ 300.9864, found: 300.9867.
4.3.7. 3-Bromo-4-p-tolyl-2H-chromen-2-one (2.3). Light yellow
solid (0.104 g, 88%); mp 158e160 ꢀC, Rf (10% ethyl acetate in hex-
ane) 0.52; IR (KBr, cmꢂ1): 1739, 1723, 1606, 1593, 1508, 1445, 1335,
1273, 1247, 1181, 1038, 987, 806, 751, 732, 624; dH NMR (500 MHz,
CDCl3): 7.57e7.53 (m, 1H, AreH), 7.40e7.36 (m, 3H, AreH),
7.20e7.16 (m, 3H, AreH), 7.11 (dd, J¼1.15, 8.05 Hz, 1H, AreH), 2.47
(s, 3H); dC NMR (125 MHz, CDCl3): 157.42, 154.79, 152.44, 139.42,
132.29, 131.94, 129.48, 128.03, 127.69, 124.61, 120.44, 116.77, 112.58,

M.L.N. Rao, A. Kumar / Tetrahedron 71 (2015) 5137e5147
5143
21.43; ESI (HRMS) (m/z) calcd for C16H12BrO2 [MþH]þ 315.0021,
CDCl3): 157.10,153.44,152.44,135.60,133.53,132.23,129.62,129.28,
found: 315.0029.
127.27, 124.83, 120.01, 116.95, 112.92; ESI (HRMS) (m/z) calcd for
C
15H9BrClO2 [MþH]þ 334.9474, found: 334.9470.
4.3.8. 3-Bromo-4-(3-methoxyphenyl)-2H-chromen-2-one
(2.4). White solid (0.079 g, 64%); mp 138e140 ꢀC, Rf (10% ethyl
acetate in hexane) 0.36; IR (KBr, cmꢂ1): 1718,1588, 1551, 1450, 1346,
1275, 1234, 1030, 998, 790, 754; dH NMR (500 MHz, CDCl3):
7.57e7.54 (m, 1H, AreH), 7.47 (t, J¼7.95 Hz, 1H, AreH), 7.40 (d,
J¼7.95 Hz, 1H, AreH), 7.20e7.17 (m, 1H, AreH), 7.11 (d, J¼7.9 Hz, 1H,
AreH), 7.06 (d, J¼7.95 Hz, 1H, AreH), 6.87 (d, J¼7.95 Hz, 1H, AreH),
6.82 (s, 1H, AreH), 3.85 (s, 3H); dC NMR (125 MHz, CDCl3): 159.80,
157.36, 154.48, 152.42, 136.46, 132.03, 130.10, 127.63, 124.70, 120.20,
116.78, 114.74, 113.67, 112.52, 55.40; ESI (HRMS) (m/z) calcd for
4.3.14. 3-Bromo-4-(4-butoxyphenyl)-2H-chromen-2-one
(2.10). White solid (0.103 g, 74%); mp 132e134 ꢀC, Rf (10% ethyl
acetate in hexane) 0.46; IR (KBr, cmꢂ1): 2961, 1731, 1720, 1609,1509,
1246,1181,1036, 990, 756; dH NMR (500 MHz, CDCl3): 7.57e7.53 (m,
1H, AreH), 7.40 (d, J¼8.55 Hz, 1H, AreH), 7.24e7.16 (m, 4H, AreH),
7.06 (d, J¼9.15 Hz, 2H, AreH), 4.05 (t, J¼6.4 Hz, 2H), 1.85e1.80 (m,
2H), 1.56e1.52 (m, 2H), 1.01 (t, J¼7.32 Hz, 3H); dC NMR (125 MHz,
CDCl3): 159.92, 157.51, 154.57, 152.45, 131.91, 129.72, 127.75, 127.05,
124.60, 120.58, 116.81, 114.65, 112.75, 67.84, 31.27, 19.26, 13.85; ESI
(HRMS) (m/z) calcd for C19H18BrO3 [MþH]þ 373.0439, found:
373.0435.
C
16H12BrO3 [MþH]þ 330.9970, found: 330.9970.
4.3.9. 3-Bromo-4-(3,4-dimethoxyphenyl)-2H-chromen-2-one
(2.5). Light yellow solid (0.103 g, 76%); mp 142e144 ꢀC, Rf (10%
ethyl acetate in hexane) 0.28; IR (KBr, cmꢂ1): 1720, 1605, 1511, 1463,
1349, 1246, 1229, 1137, 1018, 996, 807, 753, 647; dH NMR (400 MHz,
CDCl3): 7.57e7.53 (m, 1H, AreH), 7.39 (d, J¼8.24 Hz, 1H, AreH),
7.22e7.16 (m, 2H, AreH), 7.03 (d, J¼8.24 Hz, 1H, AreH), 6.86 (d,
J¼8.68 Hz,1H, AreH), 6.81 (s,1H, AreH), 3.97 (s, 3H), 3.89 (s, 3H); dC
NMR (100 MHz, CDCl3): 157.43, 154.46, 152.39, 149.67, 149.12,
131.97, 127.68, 127.48, 124.66, 120.91, 120.47, 116.78, 112.74, 111.31,
111.13, 56.07, 55.94; ESI (HRMS) (m/z) calcd for C17H14BrO4 [MþH]þ
361.0075, found: 361.0079.
4.3.15. 3-Bromo-4-(4-(trifluoromethyl)phenyl)-2H-chromen-2-one
(2.11). Light yellow solid (0.050 g, 36%); mp 132e134 ꢀC, Rf (10%
ethyl acetate in hexane) 0.48; IR (KBr, cmꢂ1): 1737,1599,1449,1324,
1175, 1121, 1109, 1068, 998, 815, 753; dH NMR (400 MHz, CDCl3):
7.85 (d, J¼8.24 Hz, 2H, AreH), 7.61e7.57 (m, 1H, AreH), 7.46e7.42
(m, 3H, AreH), 7.21 (t, J¼8.24 Hz, 1H, AreH), 6.99 (d, J¼8.24 Hz, 1H,
AreH); dC NMR (100 MHz, CDCl3): 156.95, 153.11, 152.48, 138.80,
132.39, 131.57 (q, J¼32.89 Hz), 128.72, 127.09, 126.06, 126.02,
124.93, 123.72 (q, J¼273.68 Hz), 119.79, 117.05, 112.93; EI (HRMS)
(m/z) calcd for C16H8BrF3O2 [M]þ 367.9660, found: 367.9668.
4.3.10. 3-Bromo-4-(4-ethoxyphenyl)-2H-chromen-2-one
(2.6). White solid (0.094 g, 73%); mp 140e142 ꢀC, Rf (10% ethyl
acetate in hexane) 0.38; IR (KBr, cmꢂ1): 1726,1609,1508,1244,1176,
1044, 996, 810, 751, 598; dH NMR (400 MHz, CDCl3): 7.57e7.53 (m,
1H, AreH), 7.40 (d, J¼8.24 Hz, 1H, AreH), 7.26e7.15 (m, 4H, AreH),
7.05 (d, J¼8.68 Hz, 2H, AreH), 4.13 (q, J¼7.17 Hz, 2H), 1.48 (t,
J¼7.1 Hz, 3H); dC NMR (100 MHz, CDCl3): 159.71, 157.51, 154.56,
152.45, 131.92, 129.73, 127.73, 127.12, 124.61, 120.57, 116.81, 114.64,
112.76, 63.62, 14.80; ESI (HRMS) (m/z) calcd for C17H14BrO3 [MþH]þ
345.0126, found: 345.0125.
4.3.16. 3-Bromo-4-(4-methoxyphenyl)-6-phenyl-2H-chromen-2-one
(2.12). Light brown solid (0.119 g, 78%); mp 210e212 ꢀC, Rf (10%
ethyl acetate in hexane) 0.40; IR (KBr, cmꢂ1): 1724, 1606, 1508,
1245, 1180, 1026, 991, 830, 762, 699, 646; dH NMR (500 MHz,
CDCl3): 7.77 (dd, J¼2.27, 8.57 Hz, 1H, AreH), 7.47 (d, J¼8.6 Hz, 1H,
AreH), 7.41e7.38 (m, 4H, AreH), 7.36e7.31 (m, 2H, AreH), 7.29 (d,
J¼8.6 Hz, 2H, AreH), 7.09 (d, J¼8.6 Hz, 2H, AreH), 3.91 (s, 3H); dC
NMR (125 MHz, CDCl3): 160.28, 157.45, 154.53, 151.83, 139.37,
138.06, 130.91, 129.75, 128.94, 127.78, 127.20, 127.07, 125.86, 120.74,
117.22, 114.28, 113.19, 55.37; ESI (HRMS) (m/z) calcd for C22H16BrO3
[MþH]þ 407.0283, found: 407.0287.
4.3.11. 3-Bromo-4-(4-fluorophenyl)-2H-chromen-2-one
(2.7). White solid (0.076 g, 64%); mp 126e128 ꢀC, Rf (10% ethyl
acetate in hexane) 0.50; IR (KBr, cmꢂ1): 1713, 1605, 1595, 1505,
1344, 1246, 1220, 1160, 1037, 996, 847, 812, 781, 759, 623, 551; dH
NMR (500 MHz, CDCl3): 7.59e7.55 (m, 1H, AreH), 7.41 (d,
J¼8.55 Hz, 1H, AreH), 7.31e7.19 (m, 5H, AreH), 7.07 (d, J¼8.55 Hz,
1H, AreH); dC NMR (125 MHz, CDCl3): 163.07 (d, J¼248.36 Hz),
157.21, 153.68, 152.39, 132.19, 131.06, 130.22 (d, J¼8.4 Hz), 127.36,
124.81, 120.20, 116.93, 116.16 (d, J¼21.6 Hz), 113.08; ESI (HRMS) (m/
z) calcd for C15H9BrFO2 [MþH]þ 318.9770, found: 318.9776.
4.3.17. 3-Bromo-6-phenyl-4-p-tolyl-2H-chromen-2-one
(2.13). Colorless solid (0.108 g, 74%); mp 186e188 ꢀC, Rf (10% ethyl
acetate in hexane) 0.48; IR (KBr, cmꢂ1): 1728, 1553, 1507, 1402,
1346, 1288, 1248, 1179, 1075, 986, 818, 759, 695, 629; dH NMR
(500 MHz, CDCl3): 7.76 (dd, J¼2.02, 8.57 Hz, 1H, AreH), 7.47 (d,
J¼8.6 Hz, 1H, AreH), 7.41e7.33 (m, 7H, AreH), 7.28 (d, J¼2 Hz, 1H,
AreH), 7.23 (d, J¼8.0 Hz, 2H, AreH), 2.48 (s, 3H); dC NMR (125 MHz,
CDCl3): 157.40, 154.85, 151.83, 139.52, 139.39, 138.09, 132.16, 130.96,
129.60, 128.91, 128.02, 127.76, 127.10, 125.84, 120.62, 117.18, 113.00,
21.49; ESI (HRMS) (m/z) calcd for C22H16BrO2 [MþH]þ 391.0334,
found: 391.0338.
4.3.12. 3-Bromo-4-(4-isopropoxyphenyl)-2H-chromen-2-one
(2.8). White solid (0.110 g, 82%); mp 110e112 ꢀC, Rf (10% ethyl ac-
etate in hexane) 0.42; IR (KBr, cmꢂ1): 2977, 1731, 1720, 1608, 1594,
1507, 1450, 1242, 1184, 1122, 1106, 990, 947, 815, 756, 602; dH NMR
(500 MHz, CDCl3): 7.55e7.53 (m, 1H, AreH), 7.40 (d, J¼8.55 Hz, 1H,
AreH), 7.23e7.18 (m, 4H, AreH), 7.04 (d, J¼8.55 Hz, 2H, AreH),
4.67e4.62 (m, 1H), 1.41 (d, J¼6.1 Hz, 6H); dC NMR (125 MHz, CDCl3):
158.72, 157.52, 154.57, 152.44, 131.89, 129.78, 127.76, 126.87, 124.59,
120.56, 116.79, 115.66, 112.70, 70.05, 22.03; ESI (HRMS) (m/z) calcd
for C18H16BrO3 [MþH]þ 359.0283, found: 359.0284.
4.3.18. 3-Bromo-4-(4-ethoxyphenyl)-6-phenyl-2H-chromen-2-one
(2.14). Off white solid (0.128 g, 81%); mp166e168 ꢀC, Rf (10% ethyl
acetate in hexane) 0.0.44; IR (KBr, cmꢂ1): 1727, 1608, 1508, 1470,
1250, 1179, 983, 834, 760, 693, 610; dH NMR (500 MHz, CDCl3): 7.77
(dd, J¼2.3, 8.6 Hz, 1H, AreH), 7.47 (d, J¼8.6 Hz,1H, AreH), 7.41e7.38
(m, 4H, AreH), 7.35e7.32 (m, 2H, AreH), 7.27 (d, J¼8.85 Hz, 2H,
AreH), 7.07 (d, J¼8.6 Hz, 2H, AreH), 4.13 (q, J¼6.96 Hz, 2H), 1.48 (t,
J¼6.87 Hz, 3H); dC NMR (125 MHz, CDCl3): 159.71, 157.46, 154.58,
151.82, 139.35, 138.02, 130.87, 129.73, 128.93, 127.76, 127.05, 126.99,
125.87, 120.74, 117.20, 114.68, 113.12, 63.60, 14.80; ESI (HRMS) (m/z)
calcd for C23H18BrO3 [MþH]þ 421.0439, found: 421.0437.
4.3.13. 3-Bromo-4-(4-chlorophenyl)-2H-chromen-2-one
(2.9). White solid (0.079 g, 63%); mp 124e126 ꢀC, Rf (10% ethyl
acetate in hexane) 0.48; IR (KBr, cmꢂ1): 1733,1721,1598,1485,1448,
1276,1246,1088, 991, 807, 753, 732, 616; dH NMR (500 MHz, CDCl3):
7.59e7.54 (m, 3H, AreH), 7.41 (d, J¼7.95 Hz, 1H, AreH), 7.26e7.19
(m, 3H, AreH), 7.06 (d, J¼7.95 Hz, 1H, AreH); dC NMR (125 MHz,
4.3.19. 3-Bromo-6-phenyl-4-m-tolyl-2H-chromen-2-one (2.15). Off
white solid (0.103 g, 70%); mp 120e122 ꢀC, Rf (10% ethyl acetate in
hexane) 0.52; IR (KBr, cmꢂ1): 1724, 1605, 1554, 1476, 1451, 1250,

5144
M.L.N. Rao, A. Kumar / Tetrahedron 71 (2015) 5137e5147
990, 832, 766, 700; dH NMR (500 MHz, CDCl3): 7.76 (dd, J¼2.0,
8.6 Hz, 1H, AreH), 7.48e7.44 (m, 2H, AreH), 7.40e7.32 (m, 6H,
AreH), 7.24 (d, J¼2.3 Hz, 1H, AreH), 7.12 (d, J¼7.45 Hz, 2H, AreH),
2.45 (s, 3H); dC NMR (125 MHz, CDCl3): 157.39, 154.93, 151.83,
139.37, 138.80, 138.09, 135.12, 130.98, 130.19, 128.93, 128.81, 128.46,
127.77, 127.08, 125.81, 125.01, 120.60, 117.18, 112.93, 21.54; ESI
(HRMS) (m/z) calcd for C22H16BrO2 [MþH]þ 391.0334, found:
391.0331.
ESI (HRMS) (m/z) calcd for C20H14BrO3 [MþH]þ 381.0126, found:
381.0123.
4.3.25. 3-Bromo-4-(4-ethoxyphenyl)-2H-benzo[h]chromen-2-one
(2.21). Yellow solid (0.122 g, 82%); mp 170e172 ꢀC, Rf (10% ethyl
acetate in hexane) 0.50; IR (KBr, cmꢂ1): 1726,1606,1508,1246,1177,
1041, 822, 766; dH NMR (500 MHz, CDCl3): 8.63e8.61 (m, 1H,
AreH), 7.85e7.83 (m, 1H, AreH), 7.67e7.65 (m, 2H, AreH), 7.57 (d,
J¼8.55 Hz, 1H, AreH), 7.28e7.26 (m, 2H, AreH), 7.14 (d, J¼8.55 Hz,
1H, AreH), 7.08 (d, J¼9.2 Hz, 2H, AreH), 4.15 (q, J¼6.91 Hz, 2H), 1.50
(t, J¼7.0 Hz, 3H); dC NMR (125 MHz, CDCl3): 159.69, 157.68, 155.44,
149.63, 134.71, 129.76, 129.01, 127.71, 127.54, 127.44, 124.46, 123.02,
122.83, 122.53, 115.80,114.67, 112.20, 63.63,14.81; ESI (HRMS) (m/z)
calcd for C21H16BrO3 [MþH]þ 395.0283, found: 395.0288.
4.3.20. 3-Bromo-4-(4-isopropoxyphenyl)-6-phenyl-2H-chromen-2-
one (2.16). White solid (0.129 g, 79%); mp148e150 ꢀC, Rf (10% ethyl
acetate in hexane) 0.46; IR (KBr, cmꢂ1): 1727, 1607, 1505, 1244, 1155,
992, 832, 762; dH NMR (500 MHz, CDCl3): 7.76 (dd, J¼2, 8.6 Hz, 1H,
AreH), 7.47 (d, J¼8.6 Hz, 1H, AreH), 7.41e7.40 (m, 4H, AreH),
7.35e7.34 (m, 2H, AreH), 7.27 (s, 2H, AreH), 7.05 (d, J¼8.6 Hz, 2H,
AreH), 4.69e4.62 (m, 1H), 1.41 (d, J¼6.3 Hz, 6H); dC NMR (125 MHz,
CDCl3): 158.72, 157.50, 154.60, 151.82, 139.40, 138.03, 130.89, 129.81,
128.93, 127.76, 127.09, 126.74, 125.92, 120.73, 117.20, 115.71, 113.10,
70.05, 22.04; ESI (HRMS) (m/z) calcd for C24H20BrO3 [MþH]þ
435.0596, found: 435.0597.
4.3.26. 3-Bromo-4-(4-isopropoxyphenyl)-2H-benzo[h]chromen-2-
one (2.22). Light yellow solid (0.132 g, 86%); mp 168e170 ꢀC, Rf
(10% ethyl acetate in hexane) 0.54; IR (KBr, cmꢂ1): 1727, 1607, 1507,
1241, 1120, 1099, 821, 765; dH NMR (500 MHz, CDCl3): 8.62e8.60
(m, 1H, AreH), 7.85e7.83 (m, 1H, AreH), 7.67e7.65 (m, 2H, AreH),
7.56 (d, J¼9.15 Hz, 1H, AreH), 7.27e7.25 (m, 2H, AreH), 7.16 (d,
J¼9.15 Hz, 1H, AreH), 7.06 (d, J¼9.15 Hz, 2H, AreH), 4.69e4.64 (m,
1H),1.42 (d, J¼6.1 Hz, 6H); dC NMR (125 MHz, CDCl3): 158.71,157.69,
155.45, 149.61, 134.70, 129.82, 128.99, 127.70, 127.41, 127.29, 124.43,
123.07, 122.83, 122.51, 115.80, 115.70, 112.16, 70.06, 22.06; ESI
(HRMS) (m/z) calcd for C22H18BrO3 [MþH]þ 409.0439, found:
409.0439.
4.3.21. 3-Bromo-4-(4-fluorophenyl)-6-phenyl-2H-chromen-2-one
(2.17). White solid (0.089 g, 60%); mp 156e158 ꢀC, Rf (10% ethyl
acetate in hexane) 0.56; IR (KBr, cmꢂ1): 1734, 1604, 1505, 1224,
1003, 841, 761; dH NMR (500 MHz, CDCl3): 7.78 (dd, J¼2.3, 8.6 Hz,
1H, AreH), 7.49 (d, J¼8.6 Hz, 1H, AreH), 7.41e7.38 (m, 4H, AreH),
7.36e7.33 (m, 3H, AreH), 7.30e7.26 (m, 2H, AreH), 7.20 (d,
J¼2.3 Hz, 1H, AreH); dC NMR (125 MHz, CDCl3): 163.10 (d,
J¼248.36 Hz.), 157.16, 153.70, 151.79, 139.18, 138.24, 131.14, 130.22
(d, J¼8.4 Hz), 128.99, 127.90, 127.02, 125.48, 120.41, 117.34, 116.29 (d,
J¼21.58 Hz), 113.51; ESI (HRMS) (m/z) calcd for C21H13BrFO2
[MþH]þ 395.0083, found: 395.0085.
4.3.27. 3,6-Dibromo-4-p-tolyl-2H-chromen-2-one
(2.23). White
solid (0.106 g, 72%); mp 188e190 ꢀC, Rf (10% ethyl acetate in hexane)
0.60; IR (KBr, cmꢂ1): 1721, 1593, 1545, 1466, 1398, 1262, 1246, 990,
819, 628; dH NMR (500 MHz, CDCl3): 7.64 (dd, J¼2.12, 8.82 Hz, 1H,
AreH), 7.38 (d, J¼7.9 Hz, 2H, AreH), 7.28 (d, J¼8.55 Hz, 1H, AreH),
7.21 (d, J¼2.45 Hz, 1H, AreH), 7.17 (d, J¼8.55 Hz, 2H, AreH), 2.48 (s,
3H). dC NMR (125 MHz, CDCl3): 156.79, 153.64, 151.31, 139.85,
134.75, 131.61, 129.87, 129.76, 127.93, 121.97, 118.55, 117.53, 113.95,
21.49; ESI (HRMS) (m/z) calcd for C16H11Br2O2 [MþH]þ 394.9105,
found: 394.9115.
4.3.22. 3-Bromo-4-p-tolyl-2H-benzo[h]chromen-2-one (2.18). Light
yellow solid (0.099 g, 72%); mp 186e188 ꢀC, Rf (10% ethyl acetate in
hexane) 0.56; IR (KBr, cmꢂ1): 1725, 1510, 1349, 1272, 1053, 939, 766,
752; dH NMR (500 MHz, CDCl3): 8.63e8.61 (m, 1H, AreH),
7.85e7.83 (m, 1H, AreH), 7.67e7.65 (m, 2H, AreH), 7.55 (d,
J¼9.15 Hz, 1H, AreH), 7.40 (d, J¼7.9 Hz, 2H, AreH), 7.23 (d, J¼7.9 Hz,
2H, AreH), 7.09 (d, J¼9.15 Hz, 1H, AreH), 2.49 (s, 3H); dC NMR
(125 MHz, CDCl3): 157.61, 155.69, 149.65, 139.40, 134.72, 132.73,
129.54, 129.03, 128.07, 127.72, 127.45, 124.48, 122.96, 122.81, 122.51,
115.69, 112.03, 21.47; ESI (HRMS) (m/z) calcd for C20H14BrO2
[MþH]þ 365.0177, found: 365.0174.
4.3.28. 3,6-Dibromo-4-(4-methoxyphenyl)-2H-chromen-2-one
(2.24). White solid (0.109 g, 71%); mp 158e160 ꢀC, Rf (10% ethyl
acetate in hexane) 0.52; IR (KBr, cmꢂ1): 1725, 1607, 1509, 1258, 1187,
1021, 993, 822; dH NMR (500 MHz, CDCl3): 7.64 (dd, J¼2.12, 8.82 Hz,
1H, AreH),7.29e7.22 (m, 4H, AreH), 7.09 (d, J¼9.15 Hz, 2H, AreH),
3.91 (s, 3H); dC NMR (125 MHz, CDCl3): 160.50, 156.83, 153.32,
151.30, 134.73, 129.90, 129.66, 126.59, 122.08, 118.57, 117.52, 114.47,
114.12, 55.41; ESI (HRMS) (m/z) calcd for C16H11Br2O3 [MþH]þ
410.9054, found: 410.9052.
4.3.23. 3-Bromo-4-phenyl-2H-benzo[h]chromen-2-one (2.19). Light
yellow solid (0.082 g, 62%); mp 174e176 ꢀC, Rf (10% ethyl acetate
in hexane) 0.58; IR (KBr, cmꢂ1): 1727, 1633, 1598, 1350, 1098,
1050, 936, 825, 756, 734, 700, 635; dH NMR (500 MHz, CDCl3):
8.63e8.61 (m, 1H, AreH), 7.85e7.84 (m, 1H, AreH), 7.68e7.66 (m,
2H, AreH), 7.61e7.55 (m, 4H, AreH), 7.34 (d, J¼6.7 Hz, 2H, AreH),
7.05 (d, J¼8.55 Hz, 1H, AreH); dC NMR (125 MHz, CDCl3): 157.56,
155.50, 149.69, 135.70, 134.73, 129.32, 129.08, 128.89, 128.09,
127.74, 127.49, 124.57, 122.83, 122.79, 122.49, 115.56, 112.03; ESI
(HRMS) (m/z) calcd for C19H12BrO2 [MþH]þ 351.0021, found:
351.0027.
4.3.29. 3,6-Dibromo-4-(4-ethoxyphenyl)-2H-chromen-2-one
(2.25). White solid (0.118 g, 74%); mp 160e162 ꢀC, Rf (10% ethyl
acetate in hexane) 0.54; IR (KBr, cmꢂ1): 1724,1608, 1509, 1474,1251,
1179, 996, 828, 608; dH NMR (500 MHz, CDCl3): 7.64 (dd, J¼2.3,
8.6 Hz, 1H, AreH),7.29e7.26 (m, 2H, AreH), 7.21 (d, J¼8.6 Hz, 2H,
AreH), 7.07 (d, J¼8.85 Hz, 2H, AreH), 4.14 (q, J¼6.96 Hz, 2H), 1.48 (t,
J¼7.02 Hz, 3H); dC NMR (125 MHz, CDCl3): 159.90, 156.88, 153.39,
151.26, 134.70, 129.92, 129.63, 126.34, 122.06, 118.55, 117.50, 114.84,
114.05, 63.65, 14.80; ESI (HRMS) (m/z) calcd for C17H13Br2O3
[MþH]þ 424.9211, found: 424.9216.
4.3.24. 3-Bromo-4-(4-methoxyphenyl)-2H-benzo[h]chromen-2-one
(2.20). Yellow solid (0.101 g, 70%); mp 190e192 ꢀC, Rf (10% ethyl
acetate in hexane) 0.44; IR (KBr, cmꢂ1): 1724,1607, 1510,1291, 1250,
1177, 1028, 936, 836, 820, 760, 568; dH NMR (500 MHz, CDCl3):
8.62e8.60 (m, 1H, AreH), 7.85e7.83 (m, 1H, AreH), 7.67e7.65 (m,
2H, AreH), 7.56 (d, J¼9.15 Hz, 1H, AreH), 7.29e7.26 (m, 2H, AreH),
7.14e7.09 (m, 3H, AreH), 3.92 (s, 3H); dC NMR (125 MHz, CDCl3):
160.26, 157.64, 155.36, 149.61, 134.70, 130.10, 129.77, 129.01, 127.70,
127.44, 124.47, 122.97, 122.80, 122.50, 115.76, 114.23, 112.22, 55.38;
4.3.30. 3,6-Dibromo-4-(4-isopropoxyphenyl)-2H-chromen-2-one
(2.26). White solid (0.118 g, 72%); mp 136e138 ꢀC, Rf (10% ethyl
acetate in hexane) 0.54; IR (KBr, cmꢂ1): 1731, 1608, 1508, 1466,
1254, 1184, 992, 954, 818, 727; dH NMR (500 MHz, CDCl3): 7.63 (dd,
J¼2.42, 8.72 Hz, 1H, AreH), 7.28e7.26 (m, 2H, AreH), 7.20 (d,
J¼8.9 Hz, 2H, AreH), 7.05 (d, J¼8.6 Hz, 2H, AreH), 4.67e4.63 (m,

M.L.N. Rao, A. Kumar / Tetrahedron 71 (2015) 5137e5147
5145
1H), 1.42 (d, J¼6.0 Hz, 6H); dC NMR (125 MHz, CDCl3): 158.93,
156.89, 153.40, 151.27, 134.69, 129.93, 129.69, 126.07, 122.06, 118.54,
117.49, 115.80, 114.01, 70.06, 22.04; ESI (HRMS) (m/z) calcd for
1290, 1246, 1175, 1160, 980, 819, 766; dH NMR (500 MHz, CDCl3):
7.52e7.49 (m, 1H, AreH), 7.40 (d, J¼7.95 Hz, 1H, AreH), 7.29 (dd,
J¼1.22, 7.92 Hz, 1H, AreH), 7.19e7.16 (m, 1H, AreH), 7.07e7.02 (m,
4H, AreH), 6.83 (d, J¼9.15 Hz, 2H, AreH), 6.74 (d, J¼8.55 Hz, 2H,
AreH), 4.02 (q, J¼6.91 Hz, 2H), 3.75 (s, 3H),1.41 (t, J¼7.02 Hz, 3H); dC
NMR (125 MHz, CDCl3): 161.65, 158.74, 158.71, 153.06, 150.94,
131.87, 131.10, 130.82, 127.71, 126.59, 126.42, 126.28, 123.97, 120.82,
116.67, 114.22, 113.27, 63.40, 55.10, 14.76; ESI (HRMS) (m/z) calcd for
C
18H15Br2O3 [MþH]þ 438.9367, found: 438.9381.
4.3.31. 3,6,8-Tribromo-4-(4-methoxyphenyl)-2H-chromen-2-one
(2.27). White solid (0.112 g, 61%); mp 192e194 ꢀC, Rf (10% ethyl
acetate in hexane) 0.54; IR (KBr, cmꢂ1): 1735, 1608, 1535, 1506,
1436, 1321, 1296, 1246, 1178, 1165, 1004, 847, 786, 759, 651; dH NMR
(400 MHz, CDCl3): 7.90 (d, J¼2.32 Hz, 1H, AreH), 7.22e7.19 (m, 3H,
AreH), 7.09 (d, J¼9.16 Hz, 2H, AreH), 3.91 (s, 3H); dC NMR
(100 MHz, CDCl3): 160.58, 155.87, 152.98, 148.36, 137.45, 129.60,
129.26, 126.33, 122.87, 117.30, 114.89, 114.53, 111.50, 55.41; ESI
(HRMS) (m/z) calcd for C16H10Br3O3 [MþH]þ 488.8160, found:
488.8161.
C
24H21O4 [MþH]þ 373.1440, found: 373.1443.
4.3.37. 3,4-Bis(4-ethoxyphenyl)-2H-chromen-2-one
(3.4). White
solid (0.110 g, 76%); mp 100e102 ꢀC, Rf (10% ethyl acetate in hexane)
0.26; IR (KBr, cmꢂ1): 1714, 1610, 1508, 1450, 1289, 1246, 1172, 1162,
1112,1045, 983, 820, 764, 561; dH NMR (400 MHz, CDCl3): 7.52e7.48
(m, 1H, AreH), 7.40 (d, J¼7.36 Hz, 1H, AreH), 7.29 (dd, J¼1.4,
8.24 Hz, 1H, AreH), 7.19e7.15 (m, 1H, AreH), 7.05e7.01 (m, 4H,
AreH), 6.83 (d, J¼8.72 Hz, 2H, AreH), 6.72 (d, J¼9.16 Hz, 2H, AreH),
4.04e3.94 (m, 4H), 1.43e1.35 (m, 6H); dC NMR (100 MHz, CDCl3):
161.61, 158.77, 158.17, 153.11, 150.88, 131.88, 131.06, 130.85, 127.71,
126.69, 126.54, 126.17, 123.94, 120.89, 116.68, 114.26, 113.81, 63.42,
4.3.32. 3,6,8-Tribromo-4-(4-isopropoxyphenyl)-2H-chromen-2-one
(2.28). Light yellow solid (0.129 g, 67%); mp 152e154 ꢀC, Rf (10%
ethyl acetate in hexane) 0.60; IR (KBr, cmꢂ1): 1730, 1606, 1504,
1433, 1247, 1170, 1015, 955, 840, 654; dH NMR (500 MHz, CDCl3):
7.90 (d, J¼1.85 Hz, 1H, AreH), 7.26e7.17 (m, 3H, AreH), 7.05 (d,
J¼8.55 Hz, 2H, AreH), 4.68e4.63 (m, 1H), 1.42 (d, J¼6.15 Hz, 6H); dC
NMR (125 MHz, CDCl3): 159.04, 155.94, 153.06, 148.36, 137.43,
129.65, 129.31, 125.84, 122.88, 117.28, 115.87, 114.81, 111.48, 70.09,
22.02; ESI (HRMS) (m/z) calcd for C18H14Br3O3 [MþH]þ 516.8473,
found: 516.8472.
63.28, 14.78; ESI (HRMS) (m/z) calcd for
387.1596, found: 387.1596.
C
25H23O4 [MþH]þ
4.3.38. 4-(4-Isopropoxyphenyl)-3-phenyl-2H-chromen-2-one
(3.5). White solid (0.098 g, 73%); mp 138e140 ꢀC, Rf (10% ethyl
acetate in hexane) 0.34; IR (KBr, cmꢂ1): 1707, 1604, 1508, 1448,
1242, 1117, 951, 772, 697; dH NMR (500 MHz, CDCl3): 7.54e7.51 (m,
1H, AreH), 7.42 (d, J¼8.55 Hz, 1H, AreH), 7.33 (d, J¼7.95 Hz, 1H,
AreH), 7.20e7.17 (m, 4H, AreH), 7.13 (d, J¼6.7 Hz, 2H, AreH), 7.01
(d, J¼8.55 Hz, 2H, AreH), 6.80 (d, J¼8.55 Hz, 2H, AreH), 4.54e4.49
(m, 1H), 1.32 (d, J¼5.5 Hz, 6H); dC NMR (125 MHz, CDCl3): 161.40,
157.79, 153.21, 151.48, 134.13, 131.30, 130.85, 130.57, 127.88, 127.74,
127.46, 126.77, 126.18, 124.01, 120.71, 116.72,115.41, 69.85, 21.92; ESI
4.3.33. 3,6,8-Tribromo-4-p-tolyl-2H-chromen-2-one (2.29). White
solid (0.120 g, 68%); mp 160e162 ꢀC, Rf (10% ethyl acetate in hex-
ane) 0.62; IR (KBr, cmꢂ1): 1732, 1538, 1505, 1431, 1250, 1009, 862,
844, 813, 738, 723, 651, 605, 507; dH NMR (500 MHz, CDCl3): 7.90
(d, J¼2.45 Hz, 1H, AreH), 7.38 (d, J¼7.9 Hz, 2H, AreH), 7.16e7.14
(m, 3H, AreH), 2.48 (s, 3H); dC NMR (125 MHz, CDCl3): 155.86,
153.29, 148.37, 140.05, 137.48, 131.37, 129.85, 129.22, 127.84, 122.75,
117.32, 114.74, 111.49, 21.51; ESI (HRMS) (m/z) calcd for
(HRMS) (m/z) calcd for
357.1490.
C
24H21O3 [MþH]þ 357.1491, found:
C
16H10Br3O2[MþH]þ 472.8210, found: 472.8213.
4.3.39. 4-(4-Isopropoxyphenyl)-3-(4-methoxyphenyl)-2H-chromen-
2-one (3.6). White solid (0.102 g, 70%); mp 132e134 ꢀC, Rf
(10% ethyl acetate in hexane) 0.60; IR (KBr, cmꢂ1): 2978, 1708, 1611,
1594, 1507, 1449, 1287, 1244, 1159, 981, 813, 768, 637, 594; dH NMR
(500 MHz, CDCl3): 7.52e7.48 (m, 1H, AreH), 7.40 (d, J¼8.55 Hz, 1H,
AreH), 7.31 (dd, J¼1.82, 7.92 Hz, 1H, AreH), 7.19e7.16 (m, 1H,
AreH), 7.06 (d, J¼9.15 Hz, 2H, AreH), 7.01 (d, J¼9.15 Hz, 2H, AreH)
6.82 (d, J¼8.55 Hz, 2H, AreH), 6.74 (d, J¼8.55 Hz, 2H, AreH),
4.56e4.51 (m, 1H), 3.75 (s, 3H), 1.34 (d, J¼6.15 Hz, 6H); dC NMR
(100 MHz, CDCl3): 161.65, 158.74, 157.75, 153.10, 150.96, 131.90,
131.10, 130.88, 127.76, 126.49, 126.41, 126.34, 123.96, 120.84, 116.68,
115.53, 113.27, 69.91, 55.12, 21.97; ESI (HRMS) (m/z) calcd for
4.3.34. 3,4-Bis (4-methoxyphenyl)-2H-chromen-2-one
(3.1).6a White solid (0.108 g, 80%); mp 172e174 ꢀC, Rf (10% ethyl
acetate in hexane) 0.20; IR (KBr, cmꢂ1): 1709,1610,1592,1507,1448,
1291, 1244, 1175, 1159, 1033, 980, 809, 767, 622; dH NMR (400 MHz,
CDCl3): 7.53e7.49 (m, 1H, AreH), 7.41 (d, J¼8.24 Hz, 1H, AreH), 7.28
(dd, J¼1.36, 8.24 Hz, 1H, AreH), 7.20e7.15 (m, 1H, AreH), 7.07e7.03
(m, 4H, AreH), 6.84 (d, J¼9.16 Hz, 2H, AreH), 6.74 (d, J¼8.72 Hz, 2H,
AreH), 3.80 (s, 3H), 3.75 (s, 3H); dC NMR (100 MHz, CDCl3): 161.62,
159.34, 158.73, 153.08, 150.87, 131.87, 131.11, 130.84, 127.69, 126.78,
126.49, 126.28, 123.98, 120.82, 116.69, 113.76, 113.29, 55.20, 55.11;
ESI (HRMS) (m/z) calcd for C23H19O4 [MþH]þ 359.1283, found:
359.1280.
C
25H23O4 [MþH]þ 387.1596, found: 387.1592.
4.3.35. 3-(4-Isopropoxyphenyl)-4-(4-methoxyphenyl)-2H-chro-men-
2-one (3.2). White solid (0.105 g, 72%); mp 112e114 ꢀC, Rf (10% ethyl
acetate in hexane) 0.30; IR (KBr, cmꢂ1): 1720, 1608, 1505, 1446,
1296, 1249, 1176, 1113, 982, 950, 819, 762, 572; dH NMR (500 MHz,
CDCl3): 7.52e7.49 (m, 1H, AreH), 7.41 (d, J¼8.2 Hz, 1H, AreH),
7.29e7.27 (m, 1H, AreH), 7.19e7.16 (m, 1H, AreH), 7.05e7.02 (m,
4H, AreH), 6.85e6.83 (m, 2H, AreH), 6.71e6.70 (m, 2H, AreH),
4.51e4.46 (m, 1H), 3.80 (s, 3H), 1.29 (d, J¼5.8 Hz, 6H); dC NMR
(125 MHz, CDCl3): 161.65, 159.33, 157.12, 153.07, 150.82, 131.91,
131.07, 130.86, 127.69, 126.84, 126.55, 125.98, 123.96, 120.87, 116.69,
115.06, 113.75, 69.73, 55.21, 22.02; ESI (HRMS) (m/z) calcd for
4.3.40. 3,4-Bis(4-isopropoxyphenyl)-2H-chromen-2-one
(3.7). White solid (0.114 g, 72%); mp 116e118 ꢀC, Rf (10% ethyl ac-
etate in hexane) 0.32; IR (KBr, cmꢂ1): 1706, 1606, 1506, 1450, 1290,
1248,1181,1135, 986, 952, 863, 835, 769; dH NMR (500 MHz, CDCl3):
7.52e7.48 (m, 1H, AreH), 7.40 (d, J¼8.55 Hz, 1H, AreH), 7.31 (d,
J¼7.95 Hz, 1H, AreH), 7.19e7.16 (m, 1H, AreH), 7.04e7.00 (m, 4H,
AreH), 6.81 (d, J¼8.55 Hz, 2H, AreH), 6.70 (d, J¼8.55 Hz, 2H, AreH),
4.56e4.45 (m, 2H), 1.33 (d, J¼6.1 Hz, 6H), 1.29 (d, J¼6.1 Hz, 6H); dC
NMR (100 MHz, CDCl3): 161.66, 157.71, 157.10, 153.06, 150.89,
131.92, 131.04, 130.89, 127.74, 126.52, 126.45, 126.03, 123.93, 120.85,
116.65, 115.49, 115.04, 69.88, 69.72, 22.00, 21.95; ESI (HRMS) (m/z)
calcd for C27H27O4 [MþH]þ 415.1909, found: 415.1905.
C
25H23O4 [MþH]þ 387.1596, found: 387.1594.
4.3.36. 4-(4-Ethoxyphenyl)-3-(4-methoxyphenyl)-2H-chromen-2-
one (3.3). White solid (0.104 g, 75%); mp 150e152 ꢀC, Rf (10% ethyl
acetate in hexane) 0.28; IR (KBr, cmꢂ1): 1705, 1609, 1507, 1449,
4.3.41. 4-(4-Isopropoxyphenyl)-3-(4-methoxyphenyl)-6-phenyl-2H-
chromen-2-one (3.8). White solid (0.126 g, 73%); mp 156e158 ꢀC, Rf
(10% ethyl acetate in hexane) 0.21; IR (KBr, cmꢂ1): 2978, 1718, 1608,

5146
M.L.N. Rao, A. Kumar / Tetrahedron 71 (2015) 5137e5147
1507, 1288, 1246, 1185, 1176, 1120, 980, 839, 834, 761, 695; dH NMR
(500 MHz, CDCl3): 7.73 (dd, J¼1.85, 8.55 Hz, 1H, AreH), 7.50e7.33
(m, 7H, AreH), 7.06 (t, J¼8.87 Hz, 4H, AreH), 6.83 (d, J¼8.55 Hz, 2H,
AreH), 6.75 (d, J¼9.15 Hz, 2H, AreH), 4.56e4.51 (m, 1H), 3.76 (s,
3H), 1.33 (d, J¼6.15 Hz, 6H); dC NMR (125 MHz, CDCl3): 161.59,
158.76, 157.78, 152.54, 150.98, 139.90, 137.30, 131.91, 130.92, 130.08,
128.88, 127.51, 127.07, 126.70, 126.36, 126.02, 121.00, 117.09, 115.60,
113.27, 69.93, 55.13, 21.97; ESI (HRMS) (m/z) calcd for C31H26NaO4
[MþNa]þ 485.1729, found: 485.1720.
69.94, 55.12, 21.98; ESI (HRMS) (m/z) calcd for C29H25O4 [MþH]þ
437.1753, found: 437.1759.
4.3.46. 3-Bromo-6-(4-isopropoxyphenyl)-4-(4-methoxyphenyl)-2H-
chromen-2-one (4.1). White solid (0.105 g, 60%); mp 152e154 ꢀC, Rf
(10% ethyl acetate in hexane) 0.38; IR (KBr, cmꢂ1): 1721, 1607, 1505,
1472, 1275, 1246, 1184, 1120, 1029, 983, 827; dH NMR (400 MHz,
CDCl3): 7.59 (dd, J¼2.28, 8.72 Hz, 1H, AreH), 7.38 (d, J¼2.28 Hz, 1H,
AreH), 7.28 (d, J¼8.68 Hz, 1H, AreH), 7.02 (dd, J¼2.06, 8.94 Hz, 4H,
AreH), 6.86 (d, J¼8.72 Hz, 2H, AreH), 6.71 (d, J¼8.92 Hz, 2H, AreH),
4.51e4.45 (m, 1H), 3.81 (s, 3H), 1.29 (d, J¼5.96 Hz, 6H); dC NMR
(100 MHz, CDCl3): 160.98, 159.55, 157.32, 151.90, 149.57, 133.82,
131.85, 130.76, 129.94, 127.51, 126.10, 125.47, 122.60, 118.42, 116.80,
115.06, 114.02, 69.73, 55.23, 22.00; ESI (HRMS) (m/z) calcd for
4.3.42. 3,4-Bis(4-isopropoxyphenyl)-6-phenyl-2H-chromen-2-one
(3.9). White solid (0.136 g, 74%); mp 196e198 ꢀC, Rf (10% ethyl
acetate in hexane) 0.28; IR (KBr, cmꢂ1): 2979, 1713, 1606, 1507,
1477, 1300, 1242, 1181, 1122, 989, 952, 845, 823, 766, 701; dH NMR
(400 MHz, CDCl3): 7.74e7.71 (m, 1H, AreH), 7.51e7.33 (m, 7H,
AreH), 7.05 (dd, J¼2.28, 8.68 Hz, 4H, AreH), 6.83 (d, J¼8.72 Hz,
2H, AreH), 6.72 (d, J¼8.72 Hz, 2H, AreH), 4.57e4.47 (m, 2H), 1.33
(d, J¼5.96 Hz, 6H), 1.30 (d, J¼5.96 Hz, 6H); dC NMR (100 MHz,
CDCl3): 161.58, 157.80, 157.17, 152.56, 150.93, 139.95, 137.30,
131.95, 130.94, 130.02, 128.88, 127.51, 127.08, 126.80, 126.46,
126.08, 126.01, 121.05, 117.08, 115.63, 115.11, 69.95, 69.79, 22.01,
21.97; ESI (HRMS) (m/z) calcd for C33H31O4 [MþH]þ 491.2222,
found: 491.2226.
C
25H22 BrO4 [MþH]þ 465.0701, found: 465.0705.
4.3.47. 3-(4-Ethoxyphenyl)-6-(4-isopropoxyphenyl)-4-(4-meth-oxy-
phenyl)-2H-chromen-2-one (4.2). White solid (0.061 g, 65%); mp
142e144 ꢀC, Rf (10% ethyl acetate in hexane) 0.36; IR (KBr, cmꢂ1):
1709, 1608, 1517, 1505, 1477, 1246, 1182, 1126, 821; dH NMR
(400 MHz, CDCl3): 7.68 (dd, J¼2.06, 8.46 Hz, 1H, AreH), 7.46e7.34
(m, 4H, AreH), 7.08e7.03 (m, 4H, AreH), 6.91 (d, J¼8.72 Hz, 2H,
AreH), 6.85 (d, J¼8.68 Hz, 2H, AreH), 6.71 (d, J¼8.68 Hz, 2H, AreH),
4.52e4.46 (m, 1H), 4.04 (q, J¼7.01 Hz, 2H), 3.81 (s, 3H), 1.42 (t,
J¼7.1 Hz, 3H), 1.30 (d, J¼5.96 Hz, 6H); dC NMR (100 MHz, CDCl3):
161.65, 159.34, 158.68, 157.12, 152.11, 150.91, 137.00, 132.20, 131.93,
130.88,129.68,128.05,126.80,126.05,125.33,120.99,116.99,115.08,
114.86, 113.81 69.74, 63.53, 55.20, 22.03, 14.80; ESI (HRMS) (m/z)
calcd for C33H31O5 [MþH]þ 507.2171, found: 507.2173.
4.3.43. 3-(4-Ethoxyphenyl)-4-(4-isopropoxyphenyl)-2H
benzo[h]-
chromen-2-one (3.10). Yellow solid (0.103 g, 61%); mp 164e166 ꢀC,
Rf (10% ethyl acetate in hexane) 0.26; IR (KBr, cmꢂ1): 2978, 1710,
1608, 1508, 1286, 1246, 1173, 1118, 1047, 823; dH NMR (500 MHz,
CDCl3): 8.67 (d, J¼7.35 Hz, 1H, AreH), 7.85 (d, J¼6.7 Hz, 1H, AreH),
7.66e7.62 (m, 2H, AreH), 7.57 (d, J¼8.55 Hz, 1H, AreH), 7.31 (d,
J¼8.55 Hz, 1H, AreH), 7.09 (d, J¼9.15 Hz, 2H, AreH), 7.05 (d,
J¼8.55 Hz, 2H, AreH), 6.84 (d, J¼8.55 Hz, 2H, AreH), 6.74 (d,
J¼8.55 Hz, 2H, AreH), 4.58e4.53 (m, 1H), 3.98 (q, J¼6.91 Hz, 2H),
1.39e1.34 (m, 9H); dC NMR (125 MHz, CDCl3): 161.67, 158.11, 157.71,
151.84, 150.03, 134.40, 131.95, 130.95, 128.45, 127.57, 126.99, 126.91,
126.30, 125.99, 123.61, 123.41, 123.10, 122.67, 115.98, 115.54, 113.80,
69.90, 63.28, 21.98, 14.81; ESI (HRMS) (m/z) calcd for C30H27O4
[MþH]þ 451.1909, found: 451.1904.
4.3.48. 3-Chloro-4-(4-methoxyphenyl)-2H-chromen-2-one
(5.1). White solid (0.042 g, 39%); mp 138e140 ꢀC, Rf (10% ethyl
acetate in hexane) 0.30; IR (KBr, cmꢂ1): 1729, 1607, 1507, 1349, 1247,
1175, 1040, 1015, 828, 764; dH NMR (400 MHz, CDCl3): 7.55e7.51 (m,
1H, AreH), 7.40 (d, J¼8.72 Hz, 1H, AreH), 7.29e7.27 (m, 2H, AreH),
7.23e7.18 (m, 2H, AreH), 7.09e7.07 (m, 2H, AreH), 3.90 (s, 3H); dC
NMR (125 MHz, CDCl3): 160.36, 157.58, 151.96, 150.96, 131.70,
130.05, 127.50, 125.05, 124.64, 120.54, 120.32, 116.85, 114.21, 55.37;
EI (HRMS) (m/z) calcd for C16H11ClO3 [M]þ 286.0397, found:
286.0397.
4.3.44. 3,4-Bis(4-isopropoxyphenyl)-2H-benzo[h]chromen-2-one
(3.11). Yellow solid (0.132 g, 76%); mp 124e126 ꢀC, Rf (10% ethyl
acetate in hexane) 0.28; IR (KBr, cmꢂ1): 2976, 1711, 1606, 1509,
1381, 1242, 1119, 1049, 953, 937, 832, 805, 535; dH NMR (400 MHz,
CDCl3): 8.67 (d, J¼9.16 Hz, 1H, AreH), 7.86e7.84 (m, 1H, AreH),
7.67e7.61 (m, 2H, AreH), 7.56 (d, J¼9.16 Hz, 1H, AreH), 7.31 (d,
J¼8.72 Hz, 1H, AreH), 7.09e7.04 (m, 4H, AreH), 6.84 (d, J¼8.68 Hz,
2H, AreH), 6.73 (d, J¼9.16 Hz, 2H, AreH), 4.58e4.46 (m, 2H,
AreH), 1.35 (d, J¼5.96 Hz, 6H), 1.31 (d, J¼5.92 Hz, 6H); dC NMR
(100 MHz, CDCl3): 161.66, 157.72, 157.11, 151.82, 150.02, 134.40,
131.99, 130.96, 128.44, 127.57, 126.98, 126.19, 126.01, 123.60, 123.41,
123.10, 122.66, 116.00, 115.56, 115.08, 69.92, 69.75, 22.03, 21.98; ESI
Acknowledgements
The financial support received from the Council of Scientific and
Industrial Research (CSIR), New Delhi (No. 02(0091)/12/EMR-II) is
gratefully acknowledged. A. K also acknowledges the research fel-
lowship received from the CSIR, New Delhi.
Supplementary data
Supplementary data (Supplementary data comprising 1H and
13C NMR and HRMS for all the products was given and it can be
found in the online version.) related to this article can be found at
http://dx.doi.org/10.1016/j.tet.2015.05.060.
(HRMS) (m/z) calcd for
465.2060.
C
31H29O4 [MþH]þ 465.2066, found:
4.3.45. 4-(4-Isopropoxyphenyl)-3-(4-methoxyphenyl)-2H-benzo-[h]
chromen-2-one (3.12). Light yellow solid (0.108 g, 66%); mp
182e184 ꢀC, Rf (10% ethyl acetate in hexane) 0.24; IR (KBr, cmꢂ1):
1712, 1609, 1553, 1508, 1352, 1285, 1244, 1120, 1021, 824, 777, 749;
dH NMR (400 MHz, CDCl3): 8.68e8.66 (m, 1H, AreH), 7.86e7.84 (m,
1H, AreH), 7.67e7.61 (m, 2H, AreH), 7.57 (d, J¼8.68 Hz, 1H, AreH),
7.31 (d, J¼9.12 Hz, 1H, AreH), 7.11 (d, J¼8.72 Hz, 2H, AreH), 7.05 (d,
J¼9.12 Hz, 2H, AreH), 6.85 (d, J¼9.16 Hz, 2H, AreH), 6.76 (d,
J¼8.72 Hz, 2H, AreH), 4.59e4.52 (m, 1H), 3.76 (s, 3H), 1.35 (d,
J¼6.4 Hz, 6H); dC NMR (100 MHz, CDCl3): 161.64, 158.72, 157.74,
151.87, 150.04, 134.42, 131.96, 130.94, 128.47, 127.58, 126.99, 126.90,
126.49, 125.94, 123.62, 123.40, 123.10, 122.66, 115.97, 115.57, 113.29,
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