A Regioselective Approach to C3-Aroylcoumarins via Cobalt-Catalyzed C(sp 2)-H Activation Carbonylation of Coumarins

Article abstract of DOI:10.1055/s-0037-1610702

A new cobalt-catalyzed C-H bond activation of coumarins with aryl halides or pseudohalides and carbon monoxide insertion to give various 3-aroylcoumarin derivatives is described. It is the first time that CO as C1 feedstock is used as the coupling partners in cobalt-catalyzed regioselective coumarin C-H functionalization reactions. Upon activation with manganese powder, the Co catalyzes the C-H bond activation carbonylation reactions of aryl iodides, bromides, and even triflates under mild conditions, providing the regioselective aroylated products in moderate to good yields.

Full text of DOI:10.1055/s-0037-1610702

SYNTHESIS
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© Georg Thieme Verlag Stuttgart · New York
2019, 51, A–G
paper
A
en
R. Pashazadeh et al.
Paper
Synthesis
A Regioselective Approach to C3-Aroylcoumarins via Cobalt-
Catalyzed C(sp2)–H Activation Carbonylation of Coumarins
Rahim Pashazadeh*a
0
0
0
0-0
0
0
2-
4
8
5
1-2
9
3
2
O
O
H
X
1 atm CO
Saideh Rajai-Daryasareib
Siyavash Mirzaeic
Mehdi Soheilizadd
Samira Ansarid
H
O
R2
R1
R1
R2
Co
+
O
O
X = I, Br, OTf
- C–X/C–H carbonylation - regioselective aroylation reaction
- single 3d metal catalyst - 21 different examples
- cost-effective and robust - up to 84% isolated yield
Meisam Shabaniane
a SOHA Pharmaceutical Company, PO BOX 31999-98461, Karaj, Iran
pashazadeh.rahim@yahoo.com
b School of Chemistry, College of Science, University of Tehran, Tehran, Iran
c Department of Genetics, Royan Institute for Reproductive Biomedicine,
ACECR, Tehran, Iran
d CinnaGen Medical Biotechnology Research Center, Alborz University of
Medical Sciences, Karaj, Iran
e Faculty of Chemistry and Petrochemical Engineering, Standard Research
Institute (SRI) Karaj, Karaj, Iran
Received: 22.01.2019
Accepted after revision: 12.03.2019
Published online: 02.04.2019
Table 1 Optimization of Cross-Coupling Carbonylation Reactiona
I
O
DOI: 10.1055/s-0037-1610702; Art ID: ss-2019-z0043-op
CO (1 atm)
CoBr2/Bpy(7 mol%)
+
Abstract A new cobalt-catalyzed C–H bond activation of coumarins
with aryl halides or pseudohalides and carbon monoxide insertion to
give various 3-aroylcoumarin derivatives is described. It is the first time
that CO as C1 feedstock is used as the coupling partners in cobalt-cata-
lyzed regioselective coumarin C–H functionalization reactions. Upon
activation with manganese powder, the Co catalyzes the C–H bond ac-
tivation carbonylation reactions of aryl iodides, bromides, and even tri-
flates under mild conditions, providing the regioselective aroylated
products in moderate to good yields.
Mn (3 equiv)
MeCN, 80 °C, 16 h
O
O
O
O
1a
2a
3a
Entry Catalyst system: Changes from the standard conditions Yield (%)b
1
2
none
77
ND
23
ND
62
43
40
57
65
36
46
52
63
30
45
<5
21
ND
without CoBr2
3
without 2,2′-bipyridine
without Mn powder
4
Key words cobalt-catalyzed, C–H activation, carbon monoxide,
carbonylation, 3-aroylcoumarin
5
Mn powder (2 equiv)
6
CoI2 in place of CoBr2
7
Co(OAc)2 in place of CoBr2
Co(OAc)2·4H2O in place of CoBr2
1,10-phenanthroline in place of 2,2′-bipyridine
PPh3 in place of 2,2′-bipyridine
Cu in place of Mn
The direct C–H bond activation and functionalization
method has emerged as a straightforward and step-eco-
nomical synthetic methodology for the sustainable synthe-
sis of diverse organic structures.1 Construction of C–C
bonds is one of the most facile and powerful strategies in
organic chemistry, and ether containing compounds are
widely employed in the synthesis of complex molecules and
functional materials, which this methodology facilitated by
using transition metals.2 Indeed, utilization of metal-cata-
lyzed cross-coupling reactions for the development of new
C−C bonds formation is still progressing impressively and is
certainly an undeniable strategy for the chemists. In recent
years, tremendous breakthroughs have been achieved in
transition-metal-catalyzed C–H bond carbonylation with
carbon monoxide as C1 feedstock and represents one of the
most atom-economic and efficient ways to construct car-
bonyl compounds.3 Because cobalt metal is abundant, more
8
9
10
11
12
13
14
15
16
17
18
Zn in place of Mn
toluene in place of MeCN
1,4-dioxane in place of MeCN
PhCl in place of MeCN
DMA in place of MeCN
NMP in place of MeCN
DMSO in place of MeCN
a Reaction conditions: 1a (0.6 mmol), 2a (0.5 mmol), catalyst (7.0 mol %),
solvent (3 mL), CO (1 atm), at 80 °C for 16 h in a sealed reaction tube.
b Isolated yields. ND: Not detected.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

B
R. Pashazadeh et al.
Paper
Synthesis
environmentally friendly, and less expensive compared
with noble metals, cobalt catalysts have received significant
attention due to their high activities in C–H functionaliza-
tions.4 In 1956, Murahashi and Horiie showed an elegant
method for the carbonylation reactions using a simple,
commercially available cobalt(II) precursor via chelation-
assisted C–H activation process.5 In spite of undisputed ad-
vances in the cross-coupling reactions field, Co-catalyzed
C–H carbonylation has attracted significant fondness due to
the wide presence of carbonyl groups in organic and medic-
inal chemistry.6 Particularly, C–C bond formation by using
low-valent cobalt catalysis in the presence of manganese
powder as the reducing agent has witnessed major prog-
ress, which illustrates the high importance and application
of Co(II)/Mn catalytic system in the cross-coupling reac-
tions.7 To continue our efforts on metal-free heterocyclic C–
H functionalization8 and palladium-catalyzed carbonyla-
tion aroylation of coumarins (Scheme 1a),9 we disclose here
the cobalt-catalyzed C3-aroylation of coumarins with aryl
halides and aryl triflates through an sp2 C–H bond carbon-
ylation functionalization reaction (Scheme 1b). This pro-
cess represents the first example of aroylation cross-cou-
pling reactions on a coumarin platform via a regioselective
sp2 C–H functionalization process with cobalt catalysis in a
carbon monoxide atmosphere (Scheme 1).
Upon subsequent screening of 1,10-phenanthroline and
PPh3 ligands (entries 9 and 10), we identified that 1,10-
phenanthroline has slightly higher ligand activity (entry 9)
but PPh3 afforded a lower yield of product 3a (entry 10).
Other reducing agents such as Cu and Zn powder gave 3a in
only moderate yields (entries 11 and 12). Low conversion
into 3-benzoylcoumarin (3a) was observed when other sol-
vents such as toluene, 1,4-dioxane, and PhCl were employed
(entries 13–15). It is necessary to mention that the use of
different polar aprotic solvents such as DMA, NMP, and
DMSO did not increase the yield of the desired product (en-
tries 16–18).
To know the scope of the present cobalt-catalyzed C–H
activation functionalization, various substituted aryl io-
dides 1 and coumarins 2 were tested under the optimized
reaction conditions (Scheme 2). Substrates bearing elec-
tron-donating groups, such as Me, iPr, and OMe, could par-
ticipate in the reaction smoothly to give the desired prod-
ucts 3b, 3c, and 3d , respectively, in good yields (72–82%).
Steric hindrance was observed for an electron-donating
OMe group at ortho-position of iodobenzene and relatively
lower yield was obtained (3e, 70%). Iodobenzenes bearing
electron-rich aryl groups 1f and 1g behaved similarly gen-
erating the 3-aroylcoumarins 3f,g in good yields. The halo-
gen groups (F and Cl) at the para-position were also tolerat-
ed, and the corresponding C–H activation products 3h and
3i were obtained in 68% and 72% yield, respectively. We
were pleased to find that coumarins with different substit-
uents such as 6-methyl, 7-methoxy, 6-chloro, and 6-bromo
survived well under the reaction conditions (→ 3j–o, 72–
84% yields). Pleasingly, 2-iodothiophene with coumarin
(2a) and 6-methylcoumarin (2b) survived the reaction con-
ditions and were successfully transformed into the corre-
sponding products 3p and 3q in good yields. When 6-nitro-
coumarin (2f) was examined, no desired product 3r was de-
tected.
a) Palladium catalysis
O
O
X
R1
R1
CO (1 atm)
Pd(OAc)2/BINAP
O
R3
O
O
R1
R2
+
R3
AgOAc
toluene
O
X = I, Br
O
b) Cobalt catalysis (this work)
X
O
CO (1 atm)
CoBr2/Bpy
R2
R1
R1
R2
+
Mn powder
O
MeCN
O
O
O
Furthermore, we set out to explore the scope with a
wide range of aryl bromides and aryl triflates for the carbo-
nylation coupling reaction (Scheme 3). Moderate to good
yields of coupled products were obtained with neutral, var-
ious electron-donating, and electron-deficient aryl bro-
mides, but aryl triflates proved to be less efficient as double
C–C coupling partner, resulting in the aroylated products in
low yields. However, 2,6-diisopropylphenyl triflate did not
give the 3-aroylcoumarin 3v.
To test chemoselective carbonylation mediated by CO,
we examined the benzene derivative 1k, which is substitut-
ed with two different halogens: iodide and bromide. Selec-
tive C–I bond cleavage carbonylation led to product 3w in
75% yield under the standard reaction conditions (Scheme
4).
X = I, Br, OTf
Scheme 1 Transition-metal-catalyzed coumarin C(sp2)–H bond carbo-
nylation
The regioselective aroylation of coumarin (2a) was car-
ried out under CO (1 atm) at 80 °C in the presence of Co-
Br2/Bpy10 (Bpy = 2,2′-bipyridine) and Mn powder (3.0
equiv) in acetonitrile (Table 1). Under the standard condi-
tions, 3-benzoylcoumarin (3a) was obtained in 77% yield
(Table 1, entry 1). Without CoBr2, product 3a was not ob-
tained (entry 2). In the absence of 2,2′-bipyridine, the reac-
tion led to reduced synthesis of product 3a (entry 3). With-
out the addition of Mn powder, the C–H activation aroyla-
tion did not proceed at all (entry 4). When the amount of
manganese powder was reduced to 2.0 equivalents, the
yield of 3a was decreased to 62% (entry 5). Furthermore,
use of CoI2, Co(OAc)2, and Co(OAc)2·4H2O as the cobalt
sources did not give any interesting results (entries 6–8).
Based on the above studies and relevant literature,7 a
plausible regioselective aroylation mechanism is proposed
in Scheme 5. Initially, the CoBr2/Bpy as the catalytic system
is reduced to the electron-rich Co(0) species by the manga-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

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R. Pashazadeh et al.
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Synthesis
I
O
O
CO (1 atm)
CoBr2/Bpy (7 mol%)
R1
R2
+
R2
R1
Mn (3 equiv)
MeCN, 80 °C, 16 h
O
O
O
1a-j
2a-f
3a-q
O
O
O
O
O
O
O
O
O
O
3c, 72%
3a, 77%
3b, 79%
OMe
O
O
O
O
O
O
O
O
O
O
OMe
OMe
OMe
3f, 76%
3d, 82%
3e, 70%
O
OMe
OMe
O
O
O
O
O
O
F
Cl
OMe
3i, 72%
3g, 73%
3h, 68%
O
O
O
O
O
O
O
O
O
F
OMe
3l, 79%
3j, 84%
3k, 80%
O
O
O
O
Cl
Br
O
O
O
O
O
F
MeO
Cl
3o, 72%
3m, 74%
3n, 83%
O
O
O
O
O2N
S
S
O
O
O
O
O
3r, 0%
3p, 77%
3q, 72%
Scheme 2 Carbonylation of aryl iodides with a range of coumarin derivatives. Reagents and conditions: 1 (0.6 mmol), 2 (0.5 mmol), catalyst (7.0 mol%),
MeCN (3 mL), CO (1 atm), at 80 °C for 16 h in a sealed reaction tube. Isolated yields are given.
nese reductant. The oxidative addition of the C–I bond to
low-valent cobalt occurs to form organocobalt species A,
followed by coordination and the migratory insertion of a
carbonyl moiety to generate the benzoylcobalt intermedi-
ate C. Then, the subsequent addition of Co-complex C into
the C3(sp2)−H bond of coumarin (2a) through migratory in-
sertion takes place to give rise to a coumarincobalt(II) com-
plex D, which the undergoes the -hydride elimination to
generate the aroylated product 3a and liberate the H–
Co(II)–I species E. The reduction of Co(II) E to Co(0) by Mn
continues the cycle. Finally, reduction of E with manganese
affords the corresponding zerovalent cobalt catalytic spe-
cies for regeneration.
ide as the carbonyl source. This protocol could significantly
simplify provide new insight into Co-catalyzed C–H func-
tionalization for the formation of two C–C bonds, which
paves the way for other Co-catalyzed carbon–carbon bond
cross-coupling carbonylation reactions.
All reactions were carried out in oven-dried Schlenk tubes under a CO
atmosphere using a balloon filled with CO. All chemicals were pur-
chased from Merck (Germany) and were used without further purifi-
cation. Mn powder (≥99%) was purchased from Sigma-Aldrich and
stored under a N2 atmosphere. CoBr2/Bbpy was prepared according to
a published method.10 Aryl triflates were synthesized according to lit-
erature procedures.11 Melting points were measured on an Electro-
thermal 9100 apparatus and are uncorrected. FT-IR spectra were ob-
tained on a Unicom Galaxy Series FT-IR 5000 spectrophotometer.
High-resolution mass spectra (HRMS) were measured with a Waters
Micromass GCT instrument. 1H and 13C NMR spectra were recorded
(CDCl3 solution with TMS as an internal standard) on a Bruker DRX-
In summary, we have established an efficient and con-
venient approach for the regioselective C(sp2)–H bond car-
bonylation of coumarins using stable, inexpensive, and
commercially available CoBr2 as the catalyst, Mn powder as
the best reducing agent, and easily handling carbon monox-
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

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R. Pashazadeh et al.
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Synthesis
X
O
O
CO (1 atm)
CoBr2/Bpy(7 mol%)
R1
R2
R2
R1
+
Mn (3 equiv)
MeCN, 80 °C, 16 h
O
O
O
X = Br and OTf
1
2
3
O
O
O
O
O
OMe
O
O
O
O
O
O
O
OMe
OMe
3a X = Br, 64%
X = OTf, 56%
3e X = Br, 61%
3f X = Br, 53%
X = OTf, 17%
3s X = Br, 66%
X = OTf, 50%
O
O
O
S
O
O
O
O
O
O
F
3j X = Br, 60%
X = OTf, 49%
3q X = Br, 56%
3h X = Br, 58%
O
O
iPr
O
Ar
Ar =
iPr
O
O
O
O
Cl
O
O
3t X = Br, 57%
X = OTf, 55%
3u X = Br, 62%
X = OTf, 44%
3v X = OTf, 0%
Scheme 3 Carbonylation of aryl bromides and aryl triflates with a range of coumarins. Reagents and conditions: 1 (0.6 mmol), 2 (0.5 mmol), catalyst
(7.0 mol%), MeCN (3 mL), CO (1 atm), at 80 °C for 16 h in a sealed reaction tube. Isolated yields are given.
O
CoBr2/Bpy
Mn
I
MnBr2
[Co]0Ln
O
O
Br
CO (1 atm)
CoBr2/Bpy (7 mol%)
Mn2+
Br
3w, 75%
1k
O
O
PhI 1a
+
Mn (3 equiv)
MeCN, 80 °C, 16 h
Mn
+
oxidative
addition
reductive
elimination
O
I
O
O
Ph[Co]IIILn
HCoILn
A
O
O
E
3x, Not detected
2a
CO
Ph
Scheme 4 Chemoselectivity on a single substrate. Reagents and condi-
tions: 1k (0.6 mmol), 2a (0.5 mmol), catalyst (7.0 mol%), MeCN (3 mL),
CO (1 atm), at 80 °C for 16 h in a sealed reaction tube. Isolated yields are
given.
coordination
β-hydride
elimination
O
I
3a
O
C
[Co]IILn
B
ILn
Ph
II
O
Co
O
migratory
insertion
H
Ph
H
O
500 Avance (at 500.1 and 125.8 MHz) or a Bruker DRX-300 Avance III
(at 300.1 and 75.4 MHz) instrument. Elemental analyses for C and H
were performed using an ECS 4010 CHNSO analyzer. Chromatography
columns were prepared from Merck silica gel (230–240 mesh).
O
C–H
cobaltation
II
D
Ph
Co ILn
C
2a
3-Aroylcoumarins 3; General Procedure
Scheme 5 Proposed mechanism of Co-catalyzed carbonylation reac-
In an oven-dried Schlenk tube equipped with a stir bar, CoBr2/Bpy (7
mol%, 13.1 mg), and Mn powder (1.5 mmol, 82 mg) were placed in
MeCN (1.5 mL). The reaction mixture was activated by a trace of tri-
fluoroacetic acid (0.1 mmol, 7.6 L). Then, the mixture was stirred for
10 min at r.t. In a vial, aryl halide 1 or aryl triflate 1 (0.6 mmol, 1.2
equiv) and coumarin 2 (0.5 mmol, 1.0 equiv) were dissolved in MeCN
(1.5 mL) and added to the Schlenk tube. Next, a balloon filled with CO
(1 atm) was connected to the Schlenk tube by the side tube and the
system was purged three times. The Schlenk tube was heated at 80 °C
for 16 h. When the reaction was completed (detected by TLC), the
mixture was cooled to r.t. The reaction was quenched with aq 2 N HCl
tion
or NH4Cl (20 mL) and extracted with CH2Cl2 (3 × 10 mL). The com-
bined organic layers were dried (anhyd Na2SO4) and evaporated in
vacuum. The residue was purified by column chromatography (n-
hexane/EtOAc 6:1) on silica gel to afford the corresponding 3.
3-Benzoyl-2H-chromen-2-one (3a)12a
Yield: 0.096 g (77%); white solid; mp 132–134 °C (Lit.12a mp 134–136 °C).
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

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R. Pashazadeh et al.
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Synthesis
IR (KBr): 3054, 1715, 1601, 1491, 1240, 1045, 798 cm–1
.
3-(3,4,5-Trimethoxybenzoyl)-2H-chromen-2-one (3g)
1H NMR (300.1 MHz, CDCl3):  = 8.10 (s, 1 H), 7.90 (d, J = 7.4 Hz, 2 H),
7.55–7.76 (m, 3 H), 7.49 (t, J = 7.4 Hz, 2 H), 7.28–7.46 (m, 2 H).
13C NMR (75.4 MHz, CDCl3):  = 191.7, 158.5, 154.8, 145.6, 136.2,
Yield: 0.127 g (73%); white solid; mp 208–210 °C.
IR (KBr): 3012, 2876, 1692, 1651, 1603, 1512, 1238, 1065, 790 cm–1
1H NMR (500.1 MHz, CDCl3):  = 8.08 (s, 1 H), 7.68 (td, J = 7.6, 1.5 Hz, 1
H), 7.62 (dd, J = 7.8, 1.3 Hz, 1 H), 7.43 (d, J = 8.4 Hz, 1 H), 7.38 (td, J =
7.7, 0.8 Hz, 1 H), 7.16 (s, 2 H), 3.96 (s, 3 H, OCH3), 3.89 (s, 6 H, 2 ×
OCH3).
.
133.9, 133.7, 129.6, 129.3, 128.6, 126.9, 125.0, 118.2, 116.9.
3-(4-Methylbenzoyl)-2H-chromen-2-one (3b)12b
Yield: 0.104 g (79%); colorless crystals; mp 130–132 °C (Lit.12b mp
13C NMR (125.8 MHz, CDCl3):  = 190.5, 158.5, 154.7, 153.1, 145.2,
132–133 °C).
143.5, 133.7, 131.2, 129.2, 127.2, 125.1, 118.2, 117.0, 107.3, 61.0, 56.4.
IR (KBr): 3064, 1710, 1662, 1608, 1567, 1240, 1095, 758 cm–1
.
Anal. Calcd for C19H16O6: C, 67.06; H, 4.74. Found: C, 67.21; H, 4.69.
1H NMR (300.1 MHz, CDCl3):  = 8.06 (s, 1 H), 7.80 (d, J = 7.9 Hz, 2 H),
7.59–7.67 (m, 2 H), 7.27–7.42 (m, 4 H), 2.43 (s, 3 H, CH3).
3-(4-Fluorobenzoyl)-2H-chromen-2-one (3h)12b
Yield: 0.091 g (68%); white solid; mp 162–164 °C (Lit.12b mp 167–168 °C).
13C NMR (75.4 MHz, CDCl3):  = 191.3, 158.5, 154.7, 145.1, 144.9,
IR (KBr): 3054, 1710, 1658, 1601, 1597, 1240, 1162, 761 cm–1
.
133.6, 133.5, 129.8, 129.4, 129.2, 127.2, 124.9, 118.2, 116.9, 21.8.
1H NMR (500.1 MHz, CDCl3):  = 8.12 (s, 1 H), 7.86 (dd, 3JH,H = 8.9 Hz,
4JF,H = 5.4 Hz, 2 H), 7.67 (td, J = 7.4, 1.3 Hz, 1 H), 7.62 (d, J = 7.8, 1.5 Hz,
1 H), 7.41 (d, J = 8.4 Hz, 1 H), 7.37 (td, J = 7.7, 1 Hz, 1 H), 7.11 (t, J = 8.6
Hz, 2 H).
3-(4-Isopropylbenzoyl)-2H-chromen-2-one (3c)12c
Yield: 0.105 g (72%); white solid; mp 134–136 °C (Lit.12c mp 135–136 °C).
IR (KBr): 3068, 3042, 2889, 1721, 1659, 1603, 1549, 1252, 1141, 770
cm–1
.
1
13C NMR (125.8 MHz, CDCl3):  = 190.2, 166.3 (d, JC,F = 288.0 Hz, C),
158.5, 154.8, 145.8, 133.9, 132.3 (d, 3JC,F = 9.6 Hz, 2 × CH), 129.3, 126.8,
125.1, 118.2, 116.9, 115.9 (d, 2JC,F = 22.2 Hz, 2 × CH).
1H NMR (500.1 MHz, CDCl3):  = 8.04 (s, 1 H), 7.83 (d, J = 8.2 Hz, 2 H),
7.63 (t, J = 7.9 Hz, 1 H), 7.59 (d, J = 7.7 Hz, 1 H), 7.29–7.36 (m, 4 H),
2.97 (sept, J = 6.9 Hz, 1 H, CH), 1.27 (d, J = 6.9 Hz, 6 H, 2 × CH3).
13C NMR (125.8 MHz, CDCl3):  = 191.2, 158.6, 155.6, 154.7, 145.0,
134.0, 133.5, 130.0, 129.2, 127.3, 126.8, 125.0, 118.2, 116.9, 34.4, 23.7.
3-(4-Chlorobenzoyl)-2H-chromen-2-one (3i)12b
Yield: 0.102 g (72%); white solid; mp 205–207 °C (Lit.12b mp 205–206 °C).
IR (KBr): 3069, 1715, 1659, 1607, 1571, 1231, 1074, 752 cm–1
1H NMR (300.1 MHz, CDCl3):  = 8.14 (s, 1 H), 7.83 (dd, J = 7.4, 2.5 Hz,
.
3-(4-Methoxybenzoyl)-2H-chromen-2-one (3d)12d
Yield: 0.114 g (82%); white solid; mp 171–173 °C (Lit.12d mp 174–175 °C).
2 H), 7.62–7.70 (m, 2 H), 7.32–7.57 (m, 4 H).
IR (KBr): 3075, 1714, 1643, 1605, 1587, 1256, 1166, 755 cm–1
.
13C NMR (75.4 MHz, CDCl3):  = 190.6, 158.1, 154.8, 146.2, 140.3,
1H NMR (300.1 MHz, CDCl3):  = 8.03 (s, 1 H), 7.89 (d, J = 8.8 Hz, 2 H),
7.59–7.67 (m, 2 H), 7.41 (d, J = 8.4 Hz, 1 H), 7.35 (t, J = 7.6 Hz, 1 H),
6.96 (d, J = 8.8 Hz, 2 H), 3.89 (s, 3 H, OCH3).
134.6, 133.9, 130.9, 129.4, 128.9, 126.5, 125.1, 118.1, 116.9.
3-Benzoyl-6-methyl-2H-chromen-2-one (3j)12a
Yield: 0.110 g (84%); white solid; mp 171–172 °C (Lit.12a mp 174 °C).
13C NMR (75.4 MHz, CDCl3):  = 190.0, 164.3, 158.6, 154.6, 144.7,
IR (KBr): 3094, 1726, 1659, 1612, 1490, 1250, 1152, 701 cm–1
.
133.4, 132.2, 129.1, 128.9, 127.5, 124.9, 118.3, 116.9, 113.9, 55.6.
1H NMR (300.1 MHz, CDCl3):  = 8.03 (s, 1 H), 7.87–7.89 (m, 2 H),
7.30–7.61 (m, 6 H), 2.43 (s, 3 H, CH3).
13C NMR (75.4 MHz, CDCl3):  = 191.9, 158.7, 152.9, 145.6, 145.5,
136.3, 134.9, 133.8, 129.6, 128.9, 128.6, 126.7, 117.9, 116.6, 20.8.
3-(2-Methoxybenzoyl)-2H-chromen-2-one (3e)12b
Yield: 0.098 g (70%); white solid; mp 155–156 °C (Lit.12b mp 158–159 °C).
IR (KBr): 3032, 2923, 2856, 1737, 1642, 1618, 1563, 1239, 745 cm–1
.
1H NMR (300.1 MHz, CDCl3):  = 8.18 (s, 1 H). 7.78 (dd, J = 7.6, 1.6 Hz,
1 H), 7.57–7.63 (m, 2 H), 7.54 (t, J = 7.4 Hz, 1 H), 7.32–7.40 (m, 2 H),
7.10 (t, J = 7.5 Hz, 1 H), 6.95 (d, J = 8.3 Hz, 1 H), 3.75 (s, 3 H, OCH3).
3-(4-Fluorobenzoyl)-6-methyl-2H-chromen-2-one (3k)12a
Yield: 0.112 g (80%); white solid; mp 161–163 °C (Lit.12a mp 158–160 °C).
13C NMR (75.4 MHz, CDCl3):  = 190.8, 158.9, 158.7, 154.7, 143.7,
134.4, 133.2, 130.7, 129.5, 129.4, 127.6, 124.7, 121.1, 118.7, 116.7,
111.4, 55.8.
IR (KBr): 3051, 1712, 1647, 1601, 1247, 1154, 775 cm–1
1H NMR (300.1 MHz, CDCl3):  = 8.01 (s, 1 H), 7.79 (d, J = 8.0 Hz, 2 H),
7.45 (d, J = 7.6 Hz, 1 H), 7.38 (s, 1 H), 7.20–7.31 (m, 3 H), 2.44 (s, 6 H).
.
13C NMR (75.4 MHz, CDCl3):  = 191.4, 158.8, 152.9, 145.2, 144.9,
134.8, 134.7, 133.7, 129.8, 129.3, 128.8, 127.1, 117.9, 116.6, 21.8, 20.8.
3-(3,4-Dimethoxybenzoyl)-2H-chromen-2-one (3f)12b
Yield: 0.117 g (76%); white solid; mp 196–198 °C (Lit.12b mp 193–194 °C).
IR (KBr): 3069, 3046, 1701, 1652, 1605, 1580, 1243, 1066, 782 cm–1
.
3-(4-Methoxybenzoyl)-6-methyl-2H-chromen-2-one (3l)9
1H NMR (500.1 MHz, CDCl3):  = 8.03 (s, 1 H), 7.66 (td, J = 8.7, 1.6 Hz, 1
H), 7.61 (dd, J = 7.8, 1.4 Hz, 1 H), 7.57 (d, J = 2.0 Hz, 1 H), 7.45 (dd, J =
8.4, 2.0 Hz, 1 H), 7.43 (d, J = 8.3 Hz, 1 H), 7.37 (td, J = 7.7, 1.0 Hz, 1 H),
6.90 (d, J = 8.4 Hz, 1 H), 3.98 (s, 3 H, OCH3), 3.97 (s, 3 H, OCH3).
13C NMR (125.8 MHz, CDCl3):  = 190.1, 158.7, 154.7, 154.2, 149.3,
144.5, 133.4, 129.2, 129.0, 127.6, 125.6, 125.0, 118.3, 116.9, 111.0,
109.9, 56.2, 56.1.
Yield: 0.116 g (79%); white solid; mp 204–206 °C (Lit.9 mp 206–207 °C).
IR (KBr): 3028, 1724, 1657, 1570, 1532, 1244, 1209, 738 cm–1
.
1H NMR (500.1 MHz, CDCl3):  = 2.45 (s, 3 H, CH3), 3.90 (s, 3 H, OCH3),
6.96 (d, J = 8.9 Hz, 2 H), 7.31 (d, J = 8.5 Hz, 1 H), 7.38 (s, 1 H), 7.45 (dd,
J = 8.5, 1.5 Hz, 1 H), 7.89 (d, J = 8.8 Hz, 2 H), 7.99 (s, 1 H).
13C NMR (125.8 MHz, CDCl3):  = 190.3, 164.3, 158.9, 152.9, 144.9,
134.9, 134.6, 132.3, 129.2, 128.8, 127.4, 118.1, 116.7, 113.9, 55.7, 20.9.
© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

F
R. Pashazadeh et al.
Paper
Synthesis
3-Benzoyl-7-methoxy-2H-chromen-2-one (3m)12d
Yield: 0.103 g (74%); white solid; mp 150–152 °C (Lit.12d mp 152–153 °C).
IR (KBr): 3093, 1713, 1654, 1373, 1227, 867, 765 cm–1
1H NMR (500.1 MHz, CDCl3):  = 8.09 (s, 1 H), 7.85 (dd, J = 8.2, 1.1 Hz,
2 H), 7.60 (tt, J = 7.4, 1.2 Hz, 1 H), 7.50 (d, J = 8.7 Hz, 1 H), 7.48 (t, J = 7.8
Hz, 2 H), 6.91 (dd, J = 8.7, 2.4 Hz, 1 H), 6.86 (d, J = 2.3 Hz, 1 H), 3.92 (s,
3 H, OCH3).
13C NMR (125.8 MHz, CDCl3):  = 192.1, 164.7, 158.8, 157.1, 146.6,
136.8, 133.5, 130.6, 129.6, 128.5, 122.8, 113.6, 111.9, 100.7, 56.1.
1H NMR (500.1 MHz, CDCl3):  = 8.09 (s, 1 H). 7.72 (s, 1 H), 7.68 (td, J =
8.6, 1.5 Hz, 2 H), 7.62 (dd, J = 7.8, 1.5 Hz, 1 H), 7.36–7.46 (m, 4 H), 2.43
(s, 3 H, CH3).
13C NMR (125.8 MHz, CDCl3):  = 191.9, 158.5, 154.8, 145.3, 138.6,
136.3, 134.8, 133.6, 130.0, 129.2, 128.5, 127.3, 126.9, 125.0, 118.2,
117.0, 21.4.
.
3-(4-Isopropylbenzoyl)-6-methyl-2H-chromen-2-one (3t)
Yield: 0.087 g (57%); white solid; mp 110–112 °C.
IR (KBr): 3060, 1723, 1652, 1599, 1546, 1248, 1141, 773 cm–1
.
6-Chloro-3-(4-fluorobenzoyl)-2H-chromen-2-one (3n)12a
Yield: 0.117 g (83%); white solid; mp 160–162 °C (Lit.12a mp 162–164 °C).
1H NMR (500.1 MHz, CDCl3):  = 8.01 (s, 1 H), 7.84 (d, J = 8.3 Hz, 2 H),
7.46 (dd, J = 8.5, 1.9 Hz, 1 H), 2.45 (s, 3 H), 7.38 (s, 1 H), 7.30–7.35 (m,
3 H), 3.00 (sept, J = 6.9 Hz, 1 H, CH), 1.29 (d, J = 6.9 Hz, 6 H, 2 × CH3).
13C NMR (125.8 MHz, CDCl3):  = 191.4, 158.8, 155.6, 152.9, 145.1,
134.8, 134.6, 134.0, 130.0, 128.8, 127.2, 126.8, 118.0, 116.7, 34.4, 23.7,
20.8.
IR (KBr): 3073, 1723, 1651, 1239, 1227, 685 cm–1
.
1H NMR (500.1 MHz, CDCl3):  = 8.00 (s, 1 H), 7.88 (dd, J = 8.4, 1.3 Hz,
2 H), 7.65 (td, J = 7.4, 1.3 Hz, 1 H), 7.58–7.62 (m, 2 H), 7.50 (t, J = 7.8
Hz, 2 H), 7.37 (d, J = 9.7 Hz, 1 H).
Anal. Calcd for C20H18O3: C, 78.41; H, 5.92. Found: C, 78.59; H, 5.81.
13C NMR (125.8 MHz, CDCl3):  = 191.2, 157.9, 153.1, 143.9, 135.9,
134.1, 133.5, 130.3, 129.7, 128.8, 128.3, 128.2, 119.2, 118.4.
3-(4-Chlorobenzoyl)-6-methyl-2H-chromen-2-one (3u)12a
Yield: 0.092 g (62%); white solid; mp 217–219 °C (Lit.12a mp >200 °C].
6-Bromo-3-(4-chlorobenzoyl)-2H-chromen-2-one (3o)12e
Yield: 0.118 g (72%); white solid; mp 170–172 °C (Lit.12e mp 171.2–
IR (KBr): 3065, 1711, 1662, 1698, 1512, 1238, 759 cm–1
.
1H NMR (300.1 MHz, DMSO-d6):  = 8.38 (s, 1 H), 7.94 (d, J = 8.2 Hz, 2
H), 7.45–7.75 (m, 4 H), 7.39 (d, J = 8.1 Hz, 1 H), 2.38 (s, 3 H, CH3).
13C NMR (75.4 MHz, DMSO-d6):  = 191.3, 158.7, 152.9, 146.4, 139.2,
172.1 °C).
IR (KBr): 3073, 1717, 1658, 1563, 1239, 828 cm–1
.
1H NMR (500.1 MHz, CDCl3):  = 7.99 (s, 1 H), 7.87 (dd, J = 7.3, 1.2 Hz,
2 H), 7.72–7.74 (m, 2 H), 7.63 (t, J = 7.4 Hz, 1 H), 7.49 (t, J = 7.8 Hz, 2
H), 7.30 (d, J = 8.6 Hz, 1 H).
135.9, 135.4, 134.7, 131.9, 129.9, 129.3, 126.3, 118.4, 116.6, 20.7.
3-(4-Bromobenzoyl)-2H-chromen-2-one (3w)
13C NMR (125.8 MHz, CDCl3):  = 191.2, 157.8, 153.5, 143.9, 136.3,
Yield: 0.123 g (75%); white solid; mp 236–238 °C.
135.9, 134.1, 131.4, 129.7, 128.8, 128.1, 119.7, 118.7, 117.6.
IR (KBr): 3058, 1713, 1670, 1610, 1515, 1232, 766 cm–1
1H NMR (500 MHz, CDCl3):  = 8.14 (s, 1 H), 7.89–7.86 (m, 3 H), 7.77–
.
3-(Thiophene-2-carbonyl)-2H-chromen-2-one (3p)12d
Yield: 0.098 g (77%); white solid; mp 146–148 °C (Lit.12d mp 148–150 °C).
7.73 (m, 3 H), 7.44–7.46 (d, J = 8.8 Hz, 1 H), 7.34–7.36 (t, J = 8.8 Hz, 1
IR (KBr): 3091, 1724, 1630, 1609, 1402, 1238, 758 cm–1
.
H).
1H NMR (500.1 MHz, CDCl3):  = 8.1 (s, 1 H), 7.77 (dd, J = 4.9, 0.9 Hz, 1
H), 7.72 (dd, J = 3.9, 1.0 Hz, 1 H), 7.66 (td, J = 8.6, 1.5 Hz, 1 H), 7.62 (dd,
J = 7.7, 1.2 Hz, 1 H), 7.39 (d, J = 8.4 Hz, 1 H), 7.36 (td, J = 7.6, 0.8 Hz, 1
H), 7.16 (dd, J = 4.8, 4.0 Hz, 1 H).
HRMS (ESI): m/z calcd for
327.9746.
C
16H9BrO3 [M+]: 327.9735; found:
Funding Information
13C NMR (125.8 MHz, CDCl3):  = 183.0, 158.3, 154.6, 144.8, 142.9,
135.9, 135.3, 133.8, 129.3, 128.5, 126.7, 125.1, 118.0, 116.9.
We acknowledge the financial support from the SOHA pharmaceuti-
cal company and the University of Tehran.()
6-Methyl-3-(thiophene-2-carbonyl)-2H-chromen-2-one (3q)
Yield: 0.097 g (72%); white solid; mp 140–142 °C.
IR (KBr): 3092, 2990, 2786, 1725, 1631, 1601, 1416, 1250, 726 cm–1
.
Supporting Information
1H NMR (500.1 MHz, CDCl3):  = 8.05 (s, 1 H), 7.76 (dd, J = 4.9, 1.0 Hz,
1 H), 7.72 (dd, J = 3.9, 1.0 Hz, 1 H), 7.45 (dd, J = 8.5, 2 Hz, 1 H), 7.39 (s,
1 H), 7.28 (d, J = 8.5 Hz, 1 H), 7.16 (dd, J = 4.9, 3.9 Hz, 1 H), 2.44 (s, 3 H).
Supporting information for this article is available online at
https://doi.org/10.1055/s-0037-1610702.
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13C NMR (125.8 MHz, CDCl3):  = 183.2, 158.5, 152.8, 144.9, 142.9,
135.8, 135.3, 134.9, 134.8, 128.9, 128.5, 126.6, 117.8, 116.6, 20.8.
References
Anal. Calcd for C15H10O3S: C, 66.65; H, 3.72; S, 11.86. Found: C, 66.79,
H, 3.61; S, 11.95.
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G

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Synthesis
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© Georg Thieme Verlag Stuttgart · New York — Synthesis 2019, 51, A–G