KMnO4/AcOH-mediated C3-selective direct arylation of coumarins with arylboronic acids

Article abstract of DOI:10.1039/c6ra04787d

An efficient protocol for KMnO₄/AcOH-mediated dehydrogenative direct radical arylation of coumarins with arylboronic acids to afford 3-arylcoumarin derivatives is described. A similar reaction system is also applicable to the 3-arylation of quinolinone derivatives. These KMnO₄/AcOH-mediated coupling reactions occur regioselectively at the C3 position of coumarins and quinolinones. Some notable features of this method are high efficiency, moderate to good yield, and a broad group tolerance.

Full text of DOI:10.1039/c6ra04787d

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KMnO4/AcOH-mediated C3-selective direct arylation of coumarins
with arylboronic acids
Received 00th January 20 xx,
Accepted 00th January 20xx
Jin-Wei Yuan,* Liang-Ru Yang, Qiu-Yue Yin, Pu Mao, and Ling-Bo Qu*
An efficient protocol for KMnO4/AcOH-mediated dehydrogenative direct radical arylation of coumarins with arylboronic
acids to afford 3-arylcoumarin derivatives is described. A similar reaction system is also applicable to the 3-arylation of
quinolinone derivatives. These KMnO4/AcOH-mediated coupling reactions occur regioselectively at the C3 position of
coumarins and quinolinones. Some notable features of this method are high efficiency, moderate to good yield, and a
broad groups tolerance.
DOI: 10.1039/x0xx00000x
www.rsc.org/
OH
Introduction
O
O
N
O
O
O
Coumarins are significant natural products, which display wide
and interesting pharmacological properties such as anti-breast
cancer, anti-HIV, anti-Alzheimer, vasorelaxant and anti-
aggregatory activities.1 Coumarin derivatives have proven to
be useful skeletons in organic synthesis as valuable building
blocks and in pharmaceuticals due to their biological and
physical properties. In particular, 3-arylcoumarin represents an
O
O
O
O
Inhibitor of HIV-1 replication
Vipirinin, HIV-1 inhibitor
Scheme 1. Examples of 3-arylcoumarins medical intermediate
important structural element in
oxidase B (MAO-B) inhibitor,2 a horseradish peroxidase (HRP)
inhibitor,3 an inhibitor of HIV-1 replication4
Scheme 1). As a
a selective monoamine
The general methods for the preparation of 3-arylcoumarins
were based on the palladium-catalyzed Suzuki-type coupling
reaction or Heck reaction. Matos group reported a method
toward 3-arylcoumarins by the Suzuki coupling reaction of 3-
chlorocoumarin and phenylboronic acid in the presence of
palladium complex and sodium carbonate at 110 oC for 2-3 h in
55-65 % yields.8 Wu group synthesized 3-arylcoumarins using
3-bromocoumarin derivatives and phenylboronic acid in the
presence of palladium complex and base, and Matsuura group
used 3-bromocoumarin and aromatic compounds by photo-
catalyzed coupling reaction to obtain 3-arylcoumarin
derivatives.9 Jafarpour and Messaoudi groups describeda
(
result of their expressive structural diversity, 3-arylcoumarins
have been found some possible applications in treatment of
allergic disorders, as HSP90 C-terminal inhibitors and strong
inhibitors
of
antigen-induced
RBL-2H3 mast
cell
degranulation.5 Moreover, 3-arylcoumarin derivatives are also
important class of fluorophores and found their application as
fluorescent labels in complex biological systems.6 Despite the
importance of 3-arylcoumarins, the synthesis of 3-
arylcoumarins is difficult due to the regioselective bias of 4-
arylation of coumarins.7 Thus, the development of novel,
efficient, and regioselective methods for the construction of 3-
arylcoumarins will be of great value in screening of novel
functional active molecules.
synthetic method for the preparation of 3-arylcoumarin by a
palladium-catalyzed decarboxylative coupling of coumarin-3-
carboxylic acids and aryl halides.10 Knochel group used the 3-
zincated coumarin and 4-substituted iodobenzenes through
Pd-catalyzed Negishi cross-coupling reaction to obtain 3-
arylcoumarins (Scheme 2 a).11 Direct functionalization through
HO
HO
O
O
O
O
O
metal-catalyzed double C
emerge as an alternative route for C
direct arylation approach allows for the construction of C
bonds without the need for prior functionalization of coupling
partners via metalation. synthetic method of 3-
−
H activation reactions have began to
−
C bond formation.12
A
MAO-B inhibitor
HRP inhibitor
−
C
A
arylcoumarins was described using coumarins and
arenesulfonyl chlorides or sodium arenesulfinates via
School of Chemistry and Chemical Engineering, Henan University of Technology,
Zhengzhou 450001, P.R. China. E-mail: yuanjinweigs@126.com, Fax: +86-371-
67756718; Tel: +86-371-67756718
† Electronic Supplementary Informaꢀon (ESI) available. Part of the experimental
dedail, and NMR spectra data See DOI: 10.1039/x0xx00000x
palladium-catalyzed direct C−H functionalization, Cu(OAc)2 as
the oxidant for 24 h.13 Yadav group described a direct 3-
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Journal Name
arylation of coumarins by the reaction of coumarins and Manganese(IV). The potassium permanganate/acetic acid
phenylhydeazine using K2CO3 as the base in DMSO solvent for system in an organic solvent is a powerful substitute for
4-24 h.14 You group reported synthesis of 3-arylcoumarins to Manganese(III) acetate.21 Guided by recent studies on
use coumarins and aromatic compounds by Pd(OAc)2- Manganese(III)-promoted hemolytic aromatic substitution
catalyzed coupling reaction and (NH4)2S2O8 for the oxidant in (HAS) using arylboronic acid as C-radical precursors, we
TFA for 24 h.15 Jafarpour group described a Pd(OAc)2-catalyzed decided to investigate the modular synthesis of 3-arylcoumarins
dehydrogenative 3-arylaction of coumarins using coumarins by this approach. Herein, we disclose
a KMnO4/AcOH-
and aryl compounds for the materials, and trifluoroacetic acid mediated dehydrogenative direct and regioselective radical
anhydride (TFAA) as the solvent at 120 oC for 16 h.16 3- arylation of coumarins with arylboronic acids to afford 3-
Arylcoumarins were also achieved by Pd(PPh3)4-catalyzed Heck arylcoumarin derivatives in good to high yield (Scheme 2 c).
coupling reactions between coumarins and aryliodides using
AgOAc for the base for 72 h (Scheme 2 b).17 Other procedures
Results and discussion
Table 1 Optimization of reaction conditionsa
for the synthesis of 3-arylcoumarins involving cyclization
reactions such as Pechmann, or Perkin reactions have been
published as well.18 Although all the above methodologies
have been utilized effectively for 3-arylcoumarins, some
problems exist with these procedures, such as: (1) the
prefunctionalization, and narrow scope of substrates; (2) use
of toxic ligands, strong acid solvent, high temperatures, long
reaction time and poor yields. Therefore, developing a
Oxidant
(eq.)
Temp Time Yieldb
(oC)
(h) (%)
90 1.0 43
Entry
Solvent
general and applicable strategy for
arylcoumarins is highly desirable.
a variety of 3-
1c
2d
3
−
−
CH3CN
CH3CN
CH3CN
90
90
90
90
90
90
90
80
90
120
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
1.0
0.25
0.5
2.0
22
0
Previous works:
CuSO4 (0.2)
FeCl3
4
⋅
6H2O (0.2) CH3CN
32
40
28
0
5
KMnO4 (0.2)
MnO2 (0.2)
CH3CN
CH3CN
CH3CN
CH3CN
C2H5OH
DCE
6
7
MnSO4 (0.2)
Mn(OAc)2 (0.2)
KMnO4 (0.2)
KMnO4 (0.2)
KMnO4 (0.2)
KMnO4 (0.2)
KMnO4 (0.2)
KMnO4 (2.0)
KMnO4 (2.0)
KMnO4 (2.0)
KMnO4 (2.0)
KMnO4 (2.0)
KMnO4 (2.0)
KMnO4 (2.0)
KMnO4 (2.0)
8
0
9
0
10
11
12
13
14
15
16
17
18
19
20
0
DMF
0
This work:
Dioxane 90
0
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
AcOH
120
50
30
55
62
80
78
70
85
78
20
40
60
80
100
80
80
80
Scheme 2. Synthesis of 3-arylcoumarins and 3-arylquinolines
Recently, radical C H functionalization of innately reactive
−
21
heterocycles has re-emerged as an avenue for selective, early
or late stage functionalization of pharmaceutically important
precursors and products.19 Metal-promoted radical reactions
have been achieved substantially utilizing a variety of aryl
coupling partners, in which one of the well-known examples of
this application is the Mn(OAc)3-mediated reaction.
Manganese(III) acetate is a one-electron oxidant, largely used
a
Reaction conditions: coumarins 1a (0.5 mmol, 73 mg), phenylboronic acid 2a
(1.0 mmol, 122 mg), oxidant in solvent (20 mL).
b Isolated yield.
c PdCl2 (0.1 eq) was used as the catalyst.
d Pd(OAc)2 (0.1 eq) was used as the catalyst.
Our initial experiments showed that using a PdCl2 or Pd(OAc)2
as the catalyst without the oxidant, coumarin 1a occurred with
phenylboronic acid 2a to obtain 3-phenyl coumarin 3a with a
as a radical generator that can lead to C−C bond forming
reactions.20 But, Manganese(III) acetate is not stable, and it
occurs easily disproportionated reaction to Manganese(II) and
2 | J. Name., 2013, 00, 1-9
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low yield (43% and 22%) (Table 1, entries 1 and 2). Various transformation. Gratifying, aliphatic boric acid, isopropyl boric
oxidants including CuSO4, FeCl3 6H2O, KMnO4, MnO2, MnSO4, acid could also react with coumarin to obtain 3-
⋅
and Mn(OAc)2 were added to the reaction system without the isopropylcoumarin 3zz. Unfortunately, benzyl acid failed to
catalyst, respectively. CuSO4, MnSO4, and Mn(OAc)2 were deliver the desired products with the current reaction system.
found to be ineffective (Table 1, entries 3, 7 and 8). When Various substituted coumarins were also found to be
FeCl3
phenylation of coumarin at C-3 was pleasingly achieved albeit Arylation of coumarins bearing alkyl and alkoxy proceeded
in 32%, 40%, and 28% (Table 1, entries 4-6). Among various smoothly leading to 3-arylcoumarins scaffolds 3s 3u, and 3w
⋅6H2O, KMnO4, and MnO2 were used however selective amenable to this direct C−H functionalization reaction.
,
oxidants screened, KMnO4 proved to the most effective. This in 72-93% yields. The highest yield 93% was obtained in
fact showed that the oxidant was crucial to the coupling transformation of 4-methyl-7-ethyloxycoumarin to its related
efficiency in C−H activation reactions. Subsequently, only the product 3w with an almost quantitative yield. We were
oxidant KMnO4 was used to promote the reaction without any pleased to see that even sensitive functionalities such as
catalyst. The solvent also affected the coupling reaction of hydroxyl and amino groups were also tolerated and the
coumarin and phenylboronic acid. No product was found with coupling reactions proceeded with no requisite for protection
C2H5OH, DCE, DMF or dioxane as solvent (Table 1, entries 9- of these groups (3t, 3x and 3y). This feature is ubiquitous in
12), and only low yield was obtained when CH3CN was hydroxycoumarin and aminocoumarin based biologically active
employed (Table 1, entry 5), where AcOH turned out to be the products, which eliminates the requirement of protection and
most appropriate (Table 1, entry 13). The amount of KMnO4 deprotection of hydroxyl and amino groups. Unfortunately,
was also screened. To our delight, the yield was improved to coumarin possessing an electron-withdrawing group such as -
75% when 2.0 eq KMnO4 was used, which indicated that the NO2 at the C6 position gave the desired product 3v in poor
KMnO4 played an important role in this reaction (Table S1
Supporting Information). The ratio of substrates coumarin and conditions were also applied to 4-substituted coumarins,
phenylboronic acid was investigated, and the ratio 1:2 of affording the corresponding products 3w 3x and 3y in 93%, 48%
coumarin and phenylboronic acid proved to be best result and 49% yields, respectively. Moreover, the reaction of 3-
Table S2 Supporting Information). When the reaction acetyl coumarin with phenylboronic acid led to the formation
,
yield. It is worthy of note that these standard reaction
,
(
,
temperature was increased from 20 oC to 80 oC, the yield of 3a of 3-phenylcoumarin derivative 3z with moderate yield (44%).
was enhanced from 30% to 80% (Table 1, entries 14-18). These results indicated the steric hinderance of coumarins
However, the product yields dramatically dropped if the played a weak role in this reaction.
reaction temperature continued to be increased, and 80 oC
was found to be best choice. Various reaction times were also Table 2 Synthesis of 3-arylcoumarins from coumarins and
examined, 0.5 h proved to the best appropriate and the yield arylboronic acidsa
was 85% (Table 1, entries 18-21).
With the optimum conditions in hand (Table 1, entry 20), we
next sought to explore the scope of coumarins and arylboronic
acids reaction for the construction of 3-arylcoumarins (Table
2). Accordingly, coumarin and various substituted arylboronic
acids possessing electron-donating and withdrawing groups
were employed in the reaction (Table 2, 3a-r). The results
showed that arylboronic acids with various groups including
alkyl, methoxy, halogeno, carbonyl, cyano group, aldehyde
group, and amide group were tolerated, and the reactions
were highly regioselective, where in all cases 4-arylcoumarins
were not observed. The crystallization of compound 3j from
EtOAc gave a single crystal suitable for X-ray analysis. It
illustrates the molecular structure of the substituted 3-
O
O
O
O
O
O
3a (85%b)
3b (88%)
3c (73%)
O
O
O
O
O
O
O
O
O
O
O
O
arylcoumarin 3j (Figure 1). Moreover, arylboronic acids with
3d (90%)
3e (94%)
3f (78%)
electron-donating groups (-CH3, -C(CH3)3, -OCH3, etc) could
promote the coupling reaction, and give better yields than
those with electron-withdrawing groups (-F, -Cl, -Br, -CF3, -
COCH3, -CN, -CHO, etc). Especially, 3,4,5-trimethoxy
phenylboronic acid could react with coumarin, giving 94% yield
Cl
F
O
O
O
O
O
3g (73%)
3h (61%)
3i (52%)
(
Table
established. In addition, ortho-methoxy phenylboronic acid
and -naphthaleneboronic acid underwent smoothly this
2, 3e), where an almost quantitative yield was
Br
CF3
F
α
O
O
O
O
O
O
coupling reaction to generate the corresponding products 3f
and 3g in good yield. The fact showed that the steric hindrance
of arylboronic acids did not obviously affect this
3j (55%)
3k (68%)
3l (45%)
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Journal Name
O
Cl
O
R2
Cl
H
O
R2
O
HO
HO
KMnO4, AcOH
80oC, 0.5h
R1
B
R1
+
N
R
N
R
O
O
O
O
O
O
O
4
2
5
3m (38%)
3n (43%)
3o (36%)
O
CN
NH
CHO
OCH3
O
O
O
O
O
O
H3CO
N
O
N
O
N
O
3p (28%)
3q (35%)
3r (52%)
5a (63%b)
5b (66%)
5c (73%)
O
O
O
HO
O
O
O
O
Br
3s (72%)
3t (55%)
3u (85%)
N
O
N
H
O
O2N
5d (75%)
5e (60%)
HO
O
O
O
O
O
O
O
3v (trace)
3w (93%)
3x (48%)
a Reaction conditions: a solution of KMnO4 (1.0 mmol, 158 mg) in 20 mL AcOH
was stirred under reflux until the purple color of KMnO4 turn brown (20 min).
After the reaction was cooled to room temperature, quinolinones 4 (0.5 mmol)
and arylboronic acid 2 (1.0 mmol) were added and the reaction was continued at
80 oC for 0.5 h.
O
H2N
O
O
O
O
O
O
3y (49%)
3z (44%)
3zz (52%)
b Isolated yields.
a Reaction conditions: a solution of KMnO4 (1.0 mmol, 158 mg) in 20 mL AcOH
was stirred under reflux until the purple color of KMnO4 turn brown (20 min).
After the reaction was cooled to room temperature, coumarins 1 (0.5 mmol) and
arylboronic acid 2 (1.0 mmol) were added and the reaction was continued at 80
oC for 0.5 h.
standard
H
b Isolated yields.
OH
conditions
B
eq (1)
+
TEMPO (3 eq)
O
O
OH
O
O
1a
2a
3a (Yield: < 5%)
standard
conditions
H
O
OH
OH
eq (2)
B
+
BHT (3 eq)
O
O
O
1a
2a
3a (trace)
Figure 1 X-ray crystal structure of 3j
In order to further explore the generality of this procedure, a
series of quinolinone derivatives was also investigated under
the optimal conditions (Table 3). We were pleased to observe
that the C3 position of quinolinone derivatives were
exclusively arylated, affording 3-arylquinolinones in 60-75%
Scheme 3 Mechanistic investigations of the dehydrogenative
radical coupling reaction
To investigate the reaction mechanism, some control
experiments were conducted (Scheme 3). A < 5% yield of 3a
was obtained in the presence of the radical inhibitor (2,2,6,6-
tetramethylpiperidin-1-yl)oxidanyl (TEMPO) (eq 1), and a trace
yield of 3a was produced when the radical scavenger butyleret
hydroxytoluene (BHT) was added (eq 2). These results could
yields. Notably,
N-methyl quinolinones with electron-rich
(OCH3) and electron-poor (Br) groups on the phenyl ring were
tolerated under these coupling conditions in good yield.
Quinolinone with a bromine substituent also underwent the
arylation reaction and resulted in 5d with an intact halo group
to serve as a good precursor for further functionalizations. It
was noteworthy that 2-quinolinone with a sensitive amide
group was also tolerated and the coupling reaction proceeded
with no requisite for protection of this group (5e).
indicate that the reaction might proceed via a radical pathway.
On the basis of these data and previous studies,19b,
21
a
possible reaction mechanism for the current manganese(III)-
mediated C3-position direct radical arylation of coumarins was
proposed as shown in Scheme 4. The formation of Mn(III)
species could be explained via the reaction of KMnO4 with
HOAc.21 The reaction of boronic acid
generates aryl or alkyl radical B 19b, 20b
which attacks selectively
A with Mn(III) salt
Table 3 Synthesis of 3-arylquinolinones from 2-quinolinones
and arylboronic acidsa
,
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C3-position of coumarin to give the carbon radical
by the conjugation with phenyl group. Subsequently, a single- mass spectra (HR MS) were obtained on Q-TOF instrument
electron transfer (SET) from to Mn(III) would release the using the ESI technique. IR spectra were recorded on
intermediate , simultaneously Mn(III) was reduced into Shimadazu IR-408 Fourier transform infrared
C stabilized in parts per million from tetramethylsilane. High resolution
C
D
Mn(II). After that, the intermediate
produce the C3-functionalized coumarin
D
E
loses a proton to spectrophotometer using a thin film supported on KBr pellets.
Melting points were measured on an XT4A microscopic
apparatus uncorrected.
.
General procedure for synthesis of 3-aryl coumarin
derivatives 3 (3-aryl quinolinone derivatives 5)
In a 50 mL Schlenk tube, a solution of KMnO4 (1.0 mmol, 158
mg) in 20 mL AcOH was stirred under reflux until the purple
color of KMnO4 turn brown (20 min). After the reaction was
cooled to room temperature, coumarins
1
(or quinolin
2 (1.0 mmol)
derivatives 4) (0.5 mmol) and arylboronic acid
o
were added and the reaction was continued at 80 C for 0.5 h
(monitored by TLC). The reaction mixture was diluted with
EtOAc, and neutralized with the saturated NaHCO3. The
resulting organic phase was dried over anhydrous NaSO4 and
concentrated under vacuum. The crude product was purified
by silica gel column chromatography using ethyl acetate/
petroleum ether (1:5 to 2:1) as eluant to obtain the desired
product 3 (or 5).
Scheme 4 Proposed reaction mechanism
3-Phenyl-2H-chromen-2-one (3a)
o
o
Colorless solid, mp 138-139 C (EtOAc) [lit.,18c mp 136-137 C]. IR
(KBr) ν(cm-1): 1716 (C=O), 1601, 1454 (Ar-), 1117 (C−O). H NMR
1
(400 MHz, CDCl3) δ: 7.81 (s, 1H), 7.71-7.69 (m, 2H), 7.53 (t, JH-H = 8.0
Conclusions
Hz, 2H), 7.47-7.40 (m, 3H), 7.36 (d, JH-H = 8.0 Hz, 3H), 7.29 (td, JH-H
=
In conclusion, we have successfully developed a versatile and
regioselective arylation of coumarins and quinolinones with
arylboronic acids. This protocol provides a valuable approach
to synthesize of biologically interesting 3-arylcoumarins via
KMnO4/AcOH-mediated dehydrogenative direct radical
coupling reaction. This reaction is high efficiency, moderate to
good yield, and a broad functional groups tolerance.
7.5 Hz, JH-H = 1.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ: 160.6, 153.5,
139.9 (CH), 134.7, 131.4 (CH), 128.8 (CH), 128.6 (CH), 128.5 (CH),
128.3, 127.9 (CH), 124.5 (CH), 119.7, 116.4 (CH). MS (ESI) m/z: 223.2
[M + H]+ (calcd for C15H11O2+ 223.0)
.
3-(p-Tolyl)-2H-chromen-2-one (3b)
o
o
Colorless solid, mp 160-161 C (EtOAc) [lit.,18c 158-159 C]. IR (KBr)
ν(cm-1): 1716 (C=O), 1610, 1452 (Ar-), 1113 (C−O). H NMR (400
1
Experimental
MHz, DMSO) δ: 8.19 (s, 1H), 7.75 (d, JH-H = 7.6 Hz, 1H), 7.63-7.58 (m,
3H), 7.41 (d, JH-H = 8.2 Hz, 1H), 7.36 (t, JH-H = 7.5 Hz, 1H), 7.25 (d, JH-H
= 8.0 Hz, 2H), 2.34 (s, 3H). 13C NMR (100 MHz, DMSO) δ: 160.2,
153.2, 140.3 (CH), 138.5, 132.1, 131.9 (CH), 129.2 (CH), 128.9 (CH),
128.7 (CH), 127.1, 125.0 (CH), 119.9, 116.2 (CH), 21.2 (CH3). MS (ESI)
m/z: 237.3 [M + H]+ (calcd for C16H13O2+ 237.0).
General information
Anhydrous solvents were obtained by standard procedure. All
substrates purchased from
J & K Scientific Ltd. were used
without further purification. Column chromatography was
performed using 200-300 mesh silica with the indicated
solvent system according to standard techniques. Analytical
thin-layer chromatography (TLC) was performed on precoated,
glass-backed silica gel plates. Visualization of the developed
chromatogram was performed by UV absorbance (254 nm or
365 nm). Nuclear magnetic resonance spectra were recorded
on Bruker Avance 400 MHz spectrometer. Chemical shifts for
1H NMR spectra are recorded in parts per million from
tetramethylsilane. Data were reported as follows: chemical
shift, multiplicity (s = singlet, d = doublet, t = triplet, m =
multiplet and br = broad), coupling constant in Hz and
integration. Chemical shifts for 13C NMR spectra were recorded
3-(4-(Tert-butyl)phenyl)-2H-chromen-2-one (3c)
o
o
White solid, mp 159-160 C (EtOAc) [lit.,22 154 C]. IR (KBr) ν(cm-1):
2960 (-CH3), 1716 (C=O), 1603, 1450 (Ar-), 1124 (C−O). 1H NMR (400
MHz, CDCl3) δ: 7.78 (s, 1H), 7.65 (d, JH-H = 8.5 Hz, 1H), 7.53-7.50 (m,
2H), 7.46 (d, JH-H = 8.5 Hz, 2H), 7.34 (d, JH-H = 8.0 Hz, 1H), 7.27 (td, JH-
H = 7.5 Hz, JH-H = 1.0 Hz, 1H), 1.34 (s, 9H). 13C NMR (100 MHz, CDCl3)
δ: 160.7, 153.4, 152.0, 139.3 (CH), 131.8, 131.2 (CH), 128.3, 128.2
(CH), 127.8 (CH), 125.4 (CH), 124.4 (CH), 119.7, 116.4 (CH), 34.7,
31.2 (CH3). MS (ESI) m/z: 279.2 [M + H]+ (calcd for C19H19O2+ 279.1).
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3-(4-Methoxyphenyl)-2H-chromen-2-one (3d)
Hz, CH). 19F NMR (376 MHz, CDCl3) δ: -112.3. MS (ESI) m/z: 241.1 [M
+ H]+ (calcd for C15H10FO2+ 241.0).
o
o
Colorless solid, mp 138-139 C (EtOAc) [lit.,18c 140-141 C]. IR (KBr)
ν(cm-1): 2918 (-CH3), 1716 (C=O), 1608, 1514, 1452 (Ar-), 1252, 1128
3-(4-Chlorophenyl)-2H-chromen-2-one (3i)
1
(C−O). H NMR (400 MHz, CDCl3) δ: 7.74 (s, 1H), 7.66 (d, JH-H = 8.9
o
White crystalline solid, mp 190-191 oC (EtOAc) [lit.,22 193 C]. IR
Hz, 2H), 7.52-7.46 (m, 2H), 7.33 (d, JH-H = 8.2 Hz, 1H), 7.27 (td, JH-H
7.5 Hz, JH-H = 1.1 Hz, 1H), 6.96 (d, JH-H = 8.9 Hz, 2H), 2.83 (s, 3H). 13
=
(KBr) ν(cm-1): 1711 (C=O), 1608, 1489, 1452 (Ar-), 1098 (C−O), 748
C
1
NMR (100 MHz, CDCl3) δ: 160.8, 160.1, 153.2, 138.5 (CH), 131.0
(CH), 129.8 (CH), 127.8, 127.7 (CH), 127.1, 124.4 (CH), 119.8, 116.3
(CH), 113.9 (CH), 55.3 (CH3). MS (ESI) m/z: 253.4 [M + H]+ (calcd for
C16H13O3+ 253.0).
(C−Cl). H NMR (400 MHz, CDCl3) δ: 7.81 (s, 1H), 7.65 (d, JH-H = 8.5
Hz, 2H), 7.55-7.51 (m, 2H), 7.40 (d, JH-H = 8.6 Hz, 2H), 7.35 (d, JH-H
=
8.6 Hz, 1H), 7.30 (td, JH-H = 8.5 Hz, JH-H = 0.9 Hz, 1H). 13C NMR (100
MHz, CDCl3) δ: 160.4, 153.5, 139.9 (CH), 134.9, 133.0, 131.7 (CH),
129.8 (CH), 128.7 (CH), 128.0 (CH), 127.1, 124.6 (CH), 119.5, 116.5
(CH). MS (ESI) m/z: 257.3 [M + H]+ (calcd for C15H10ClO2+ 257.0).
3-(3,4,5-Trimethoxyphenyl)-2H-chromen-2-one (3e)
White solid, mp 147-148 oC (EtOAc) [lit.,16 145-147 oC]. IR (KBr)
ν(cm-1): 2964, 2941 (-CH3), 1716 (C=O), 1606, 1588, 1508, 1450 (Ar-
), 1242, 1126 (C−O). 1H NMR (400 MHz, CDCl3) δ: 7.81 (s, 1H), 7.56-
3-(4-Bromophenyl)-2H-chromen-2-one (3j)
o
o
Colorless solid, mp 189-190 C (EtOAc) [lit.,18c 188-189 C]. IR (KBr)
7.50 (m, 2H), 7.33 (d, JH-H = 8.2 Hz, 1H), 7.29 (td, JH-H = 7.4 Hz, JH-H
=
ν(cm-1): 1712 (C=O), 1610, 1487, 1450 (Ar-), 1012 (C−O). H NMR
1
1.0 Hz, 1H), 6.94 (s, 2H), 3.91 (s, 6H), 3.89 (s, 3H). 13C NMR (100
MHz, CDCl3) δ: 160.5, 153.3, 153.0, 139.5 (CH), 138.7, 131.4 (CH),
130.1, 128.0, 127.9 (CH), 124.5 (CH), 119.5, 116.3 (CH), 106.0 (CH),
60.8 (CH3), 56.2 (CH3). MS (ESI) m/z: 313.0 [M + H]+ (calcd for
C18H17O5+ 313.1).
(400 MHz, CDCl3) δ: 7.81 (s, 1H), 7.60-7.52 (m, 6H), 7.35 (d, JH-H = 8.7
Hz, 1H), 7.30 (td, JH-H = 8.6 Hz, JH-H = 1.0 Hz, 1H). 13C NMR (100 MHz,
CDCl3) δ: 160.2, 153.5, 139.9 (CH), 133.5, 131.7 (CH), 131.6 (CH),
130.1 (CH), 128.0 (CH), 127.1, 124.6 (CH), 123.1, 119.5, 116.5 (CH).
MS (ESI) m/z: 301.1 [M + H]+ (calcd for C15H10BrO2+ 301.0).
3-(2-Methoxyphenyl)-2H-chromen-2-one (3f)
3-(3-Fluorophenyl)-2H-chromen-2-one (3k)
White solid, mp 138-139 oC (EtOAc) [lit.,23 140-141 oC]. IR (KBr)
o
Colorless solid, mp 173-174 C. IR (KBr) ν(cm-1): 1709 (C=O), 1610,
1
ν(cm-1): 1722 (C=O), 1608, 1491, 1456 (Ar-), 1246, 1130 (C−O). H
1
1588, 1456 (Ar-), 1180 (C−O). H NMR (400 MHz, CDCl3) δ: 7.83 (s,
NMR (400 MHz, CDCl3) δ: 7.73 (s, 1H), 7.49 (d, JH-H = 7.4 Hz, 2H),
7.38-7.34 (m, 3H), 7.27 (t, JH-H = 7.4 Hz, 1H), 7.02 (t, JH-H = 7.5 Hz,
1H), 6.99 (d, JH-H = 8.2 Hz, 1H), 3.82 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ: 160.2, 157.3, 153.7, 141.7 (CH), 131.1 (CH), 130.7 (CH),
130.2 (CH), 127.8 (CH), 126.6, 124.2 (CH), 124.1, 120.6 (CH), 119.5,
116.5 (CH), 111.4 (CH), 55.7 (CH3). MS (ESI) m/z: 253.2 [M + H]+
(calcd for C16H13O3+ 253.1).
1H), 7.54 (t, JH-H = 7.4 Hz, 2H), 7.47 (t, JH-H = 7.5 Hz, 2H), 7.43-7.39
(m, 1H), 7.36 (d, JH-H = 8.6 Hz, 1H), 7.30 (d, JH-H = 7.9 Hz, 1H), 7.09
(td, JH-H = 8.6 Hz, JH-H = 1.8 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ:
162.6(d, JF-C = 244.4 Hz), 160.2, 153.5, 140.4 (CH), 136.6 (d, JF-C = 8.2
Hz), 131.8 (CH), 130.0 (d, JF-C = 8.2 Hz, CH), 128.1 (CH), 127.0 (d, JF-C
= 2.2 Hz, CH), 124.6 (CH), 124.1 (d, JF-C = 2.9 Hz, CH), 119.4, 116.5
(CH), 115.8 (d, JF-C = 8.8 Hz, CH), 115.6 (d, JF-C = 10.7 Hz, CH). 19F
NMR (376 MHz, CDCl3) δ: -112.6. HR MS (ESI) m/z: 241.0655 [M +
H]+ (calcd for C15H10FO2+ 241.0659).
3-(Naphthalen-1-yl)-2H-chromen-2-one (3g)
Yellow solid, mp 145-146 oC (EtOAc) [lit.,23 154-156 oC]. IR (KBr)
1
ν(cm-1): 1712 (C=O), 1606, 1454 (Ar-), 1132 (C−O). H NMR (400
3-(4-(Trifluoromethyl)phenyl)-2H-chromen-2-one (3l)
MHz, CDCl3) δ: 7.89 (td, JH-H = 6.8 Hz, JH-H = 1.9 Hz, 2H), 7.78 (s, 1H),
7.77 (dd, JH-H = 8.2 Hz, JH-H = 1.3 Hz, 1H), 7.56-7.46 (m, 6H), 7.43 (t,
White solid, mp 197-198 oC (EtOAc) [lit.,18c 196-197 oC]. IR (KBr)
1
ν(cm-1): 1709 (C=O), 1608, 1456, 1356 (Ar-), 1101 (C−O). H NMR
J
H-H = 8.5 Hz, 1H), 7.30 (td, JH-H = 7.6 Hz, JH-H = 1.1 Hz, 1H). 13C NMR
(400 MHz, CDCl3) δ: 7.88 (s, 1H), 7.83 (d, JH-H = 8.1 Hz, 2H), 7.70 (d,
JH-H = 8.2 Hz, 2H), 7.59-7.55 (m, 2H), 7.38 (d, JH-H = 8.7 Hz, 1H), 7.33
(td, JH-H = 8.5 Hz, JH-H = 1.0 Hz, 1H). 13C NMR (100 MHz, CDCl3) δ:
160.2, 153.7, 140.9 (CH), 138.2, 132.1 (CH), 130.7 (d, JF-C = 31.2 Hz),
128.9 (CH), 128.2 (CH), 128.0, 126.9, 125.4 (d, JF-C = 3.7 Hz, CH),
124.7 (CH), 119.3, 116.6 (CH). 19F NMR (376 MHz, CDCl3) δ: -62.7.
MS (ESI) m/z: 291.2 [M + H]+ (calcd for C16H10F3O2+ 291.0).
(100 MHz, CDCl3) δ: 160.8, 154.0, 142.8 (CH), 133.7, 132.7, 131.7
(CH), 131.6, 129.4 (CH), 128.6 (CH), 128.3, 128.0 (CH), 127.7 (CH),
126.5 (CH), 126.1 (CH), 125.3 (CH), 125.1 (CH), 124.6 (CH), 119.3,
116.7 (CH). MS (ESI) m/z: 273.2 [M + H]+ (calcd for C19H13O2+ 273.1).
3-(4-Fluorophenyl)-2H-chromen-2-one (3h)
o
White Colorless solid, mp 188-189 C (EtOAc) [lit.,18c 196-197 oC]. IR
(KBr) ν(cm-1): 1712 (C=O), 1604, 1514, 1454 (Ar-), 1236 (C−F), 1128
Methyl 4-(2-oxo-2H-chromen-3-yl)benzoate (3m)
1
(C−O). H NMR (400 MHz, CDCl3) δ: 7.79 (s, 1H), 7.71-7.68 (m, 2H),
o
o
Colorless solid, mp 209-210 C (EtOAc) [lit.,18c 209-210 C]. IR (KBr)
7.53 (td, JH-H = 7.5 Hz, JH-H = 1.4 Hz, 2H), 7.36 (d, JH-H = 8.1 Hz, 1H),
7.30 (td, JH-H = 8.5 Hz, JH-H = 1.0 Hz, 1H), 7.15-7.11 (m, 2H). 13C NMR
(100 MHz, CDCl3) δ: 163.1(d, JF-C = 247.3 Hz), 160.5, 153.4, 139.7
(CH), 131.5 (CH), 130.7 (d, JF-C = 3.1 Hz), 130.4 (d, JF-C = 8.1 Hz, CH),
127.9 (CH), 127.3, 124.6 (CH), 119.5, 116.5 (CH), 115.5 (d, JF-C = 3.1
ν(cm-1): 1716, 1682 (C=O), 1604, 1454 (Ar-), 1109 (C−O). H NMR
1
(400 MHz, CDCl3) δ: 8.11 (dd, JH-H = 8.4 Hz, JH-H = 1.8 Hz, 2H), 7.89 (s,
1H), 7.80 (dd, JH-H = 8.3 Hz, JH-H = 1.8 Hz, 2H), 7.57 (td, JH-H = 7.5 Hz,
JH-H = 1.6 Hz, 2H), 7.39 (d, JH-H = 8.6 Hz, 1H), 7.32 (t, JH-H = 7.1 Hz,
6 | J. Name., 2013, 00, 1-9
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1H), 3.94 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 166.6, 160.1, 153.7, 1.4Hz, 1H), 7.42-7.33 (m, 4H). 13C NMR (100 MHz, DMSO) δ: 168.9,
140.8 (CH), 139.1, 131.9 (CH), 130.2, 129.7 (CH), 128.5 (CH), 128.1 160.0, 153.4, 140.9 (CH), 139.6, 135.4, 132.1 (CH), 129.0 (CH), 128.9
(CH), 127.3, 124.7 (CH), 119.4, 116.5 (CH), 52.2 (CH3). MS (ESI) m/z: (CH), 127.2, 125.0 (CH), 123.6 (CH), 119.8, 119.7 (CH), 119.6 (CH),
281.3 [M + H]+ (calcd for C17H13O4+ 281.1).
116.2 (CH), 24.4 (CH3). HR MS (ESI) m/z: 280.0966 [M + H]+ (calcd
for C17H14NO3+ 280.0968).
3-(4-Acetylphenyl)-2H-chromen-2-one (3n)
6-Methyl-3-phenyl-2H-chromen-2-one (3s)
o
o
Colorless solid, mp 217-218 C (EtOAc) [lit.,24 225-227 C]. IR (KBr)
o
o
ν(cm-1): 2920 (-CH3), 1730, 1676 (C=O), 1604, 1574, 1454 (Ar-), 1111 Colorless solid, mp 148-149 C (EtOAc) [lit.,15 149-150 C]. IR (KBr)
(C−O). H NMR (400 MHz, CDCl3) δ: 8.02 (d, JH-H = 8.2 Hz, 2H), 7.90 ν(cm-1): 2916, 2848 (-CH3), 1720 (C=O), 1616, 1577, 1448 (Ar-), 1111
1
1
(s, 1H), 7.82 (d, JH-H = 8.2 Hz, 2H), 7.57 (t, JH-H = 7.6 Hz, 2H), 7.38(d, (C−O). H NMR (400 MHz, CDCl3) δ: 7.74 (s, 1H), 7.70-7.67 (m, 2H),
JH-H = 8.2 Hz, 1H), 7.32 (t, JH-H = 7.5 Hz, 1H), 2.63 (s, 3H). 13C NMR 7.46-7.37 (m, 3H), 7.33-7.31 (m, 2H), 7.24 (dd, JH-H = 7.4 Hz, JH-H
=
(100 MHz, CDCl3) δ: 197.5, 160.1, 153.7, 140.8 (CH), 139.2, 137.0, 1.6 Hz, 1H), 2.41 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 160.8, 151.6,
132.0 (CH), 128.7 (CH), 128.4, 128.1 (CH), 127.1, 124.7 (CH), 119.4, 139.9 (CH), 134.8, 134.1, 132.4 (CH), 128.7 (CH), 128.5 (CH), 128.4
116.5 (CH), 26.7 (CH3). MS (ESI) m/z: 265.3 [M + H]+ (calcd for (CH), 128.2, 127.7 (CH), 119.4, 116.1 (CH), 20.8 (CH3). MS (ESI) m/z:
C17H13O3+ 265.1).
237.2 [M + H]+ (calcd for C16H13O2+ 237.1).
3-(3,4-Dichlorophenyl)-2H-chromen-2-one (3o)
7-Hydroxy-3-phenyl-2H-chromen-2-one (3t)
Yellow solid, mp 233-234 oC (EtOAc) [lit.,25 191-192 oC]. IR (KBr) White solid, mp 201-202 oC (EtOAc) [lit.,16 203-204 oC]. IR (KBr)
ν(cm-1): 1697 (C=O), 1606, 1473, 1452 (Ar-), 1028 (C−O), 752 (C−Cl). ν(cm-1): 3228 (-OH), 1680 (C=O), 1615, 1595, 1570, 1445 (Ar-), 1080
1H NMR (400 MHz, CDCl3) δ: 7.84-7.83 (m, 2H), 7.61-7.51 (m, 4H), (C−O). 1H NMR (400 MHz, DMSO) δ: 10.66 (s, 1H), 8.15 (s, 1H), 7.69
7.38 (d, JH-H = 8.6 Hz, 1H), 7.32 (td, JH-H = 7.7 Hz, JH-H = 0.6 Hz, 1H). (d, JH-H = 7.3 Hz, 2H), 7.60 (d, JH-H = 8.5 Hz, 1H), 7.43 (d, JH-H = 7.6 Hz,
13C NMR (100 MHz, CDCl3) δ: 160.0, 153.6, 140.4 (CH), 134.5, 133.1, 2H), 7.37 (t, JH-H = 7.3 Hz, 1H), 6.82 (dd, JH-H = 8.5 Hz, JH-H = 2.2 Hz,
132.7, 132.0 (CH), 130.4 (CH), 130.3 (CH), 128.1 (CH), 127.8 (CH), 1H), 6.76 (d, JH-H = 2.0 Hz, 1H). 13C NMR (100 MHz, DMSO) δ: 161.7,
125.9, 124.7 (CH), 119.2, 116.6 (CH). MS (ESI) m/z: 291.2 [M + H]+ 160.6, 155.3, 141.6 (CH), 135.6, 130.4 (CH), 128.7 (CH), 128.6 (CH),
(calcd for C15H9Cl2O2+ 291.0).
128.5 (CH), 122.6, 113.8 (CH), 112.4 (CH), 102.2 (CH). MS (ESI) m/z:
239.1 [M + H]+ (calcd for C15H11O3+ 239.0).
4-(2-Oxo-2H-chromen-3-yl)benzonitrile (3p)
7-Methoxy-3-phenyl-2H-chromen-2-one (3u)
Light yellow solid, mp 239-240 oC (EtOAc) [lit.,26 152-154 oC]. IR
1
o
o
(KBr) ν(cm-1): 1709 (C=O), 1614, 1446 (Ar-), 1115 (C−O). H NMR Light yellow solid, mp 119-120 C (EtOAc) [lit.,18c 118-119 C]. IR
(400 MHz, CDCl3) δ: 7.90 (s, 1H), 7.85 (d, JH-H = 8.4 Hz, 2H), 7.74 (d, (KBr) ν(cm-1): 3053, 2970 (-CH3), 1716 (C=O), 1614, 1506, 1464,
1
JH-H = 8.4 Hz, 2H), 7.59 (d, JH-H = 7.5 Hz, 2H), 7.39 (d, JH-H = 8.4 Hz, 1439 (Ar-), 1120 (C−O). H NMR (400 MHz, CDCl3) δ: 7.75 (s, 1H),
1H), 7.34 (td, JH-H = 8.4 Hz, JH-H = 0.7 Hz, 1H). 13C NMR (100 MHz, 7.68 (d, JH-H = 8.4 Hz, 2H), 7.45-7.41 (m, 3H), 7.39-7.35 (m, 1H), 6.87-
CDCl3) δ: 159.9, 153.7, 141.3 (CH), 139.1 (CH), 132.4 (CH), 132.2 6.84 (m, 2H), 3.87 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 162.6,
(CH), 129.2 (CH), 128.3 (CH), 126.4, 124.8 (CH), 119.2, 118.5, 116.6 160.8, 155.3, 139.9 (CH), 135.0, 128.8 (CH), 128.4 (CH), 124.8,
+
(CH), 112.4. MS (ESI) m/z: 248.2 [M + H]+ (calcd for C16H10NO2
248.0).
113.3, 112.7 (CH), 100.4 (CH), 55.7 (CH3). MS (ESI) m/z: 253.3 [M +
H]+ (calcd for C16H13O3+ 253.1).
4-(2-Oxo-2H-chromen-3-yl)benzaldehyde (3q)
7-Ethoxy-4-methyl-3-phenyl-2H-chromen-2-one (3w)
o
Colorless solid, mp 202-203 oC (EtOAc). IR (KBr) ν(cm-1): 1710 (C=O), Yellow solid, mp 117-118 C. IR (KBr) ν(cm-1): 3062, 2979, 2947 (-
1611, 1434 (Ar-), 1113 (C−O). 1H NMR (400 MHz, DMSO) δ: 10.06 (s, CH3), 1712 (C=O), 1604, 1508, 1385, 1361 (Ar-), 1074 (C−O). 1H NMR
1H), 8.41 (s, 1H), 8.01-7.96 (m, 4H), 7.82 (d, JH-H = 7.5 Hz, 1H), 7.66 (400 MHz, CDCl3) δ: 7.52 (d, JH-H = 8.8 Hz, 1H), 7.41 (d, JH-H = 7.0 Hz,
(t, JH-H = 7.5 Hz, 1H), 7.46 (d, JH-H = 8.3 Hz, 1H), 7.41 (t, JH-H = 7.5 Hz, 2H), 7.35 (d, JH-H = 7.3 Hz, 1H), 7.29-7.25 (m, 2H), 6.85 (dd, JH-H = 8.8
1H). 13C NMR (100 MHz, DMSO) δ: 193.2 (CHO), 159.8, 153.6, 142.5 Hz, JH-H = 2.5 Hz, 1H), 6.79 (d, JH-H = 2.2 Hz, 1H), 4.06 (q, JH-H = 7.0 Hz,
(CH), 140.9, 136.2, 132.8 (CH), 129.7 (CH), 129.6 (CH), 129.4 (CH), 2H), 2.23 (s, 3H), 1.43 (t, JH-H = 7.0 Hz, 3H). 13C NMR (100 MHz,
126.2, 125.2 (CH), 119.7, 116.4 (CH). HR MS (ESI) m/z: 251.0707 [M CDCl3) δ: 161.7, 161.3, 154.3, 148.0, 134.7, 130.2 (CH), 128.3 (CH),
+ H]+ (calcd for C16H11NO3+ 251.0703).
127.9 (CH), 126.1 (CH), 124.0, 113.9, 112.6 (CH), 101.0 (CH), 64.1
(CH2), 16.5 (CH3), 14.6 (CH3). HR MS (ESI) m/z: 281.1175 [M + H]+
(calcd for C18H17O3+ 281.1172).
N-(4-(2-Oxo-2H-chromen-3-yl)phenyl)acetamide (3r)
Light yellow solid. IR (KBr) ν(cm-1): 3300 (NH), 1708 (C=O), 1660
(C=O), 1605, 1430 (Ar-). H NMR (400 MHz, DMSO) δ: 10.08 (s, 1H),
7-Hydroxy-4-methyl-3-phenyl-2H-chromen-2-one (3x)
1
8.17 (s, 1H), 7.93 (s, 1H), 7.76 (dd, JH-H = 7.7 Hz, JH-H = 1.1 Hz, 1H), White solid, mp 231-232 oC (EtOAc) [lit.,27 225-227 oC]. IR (KBr)
7.70 (dd, JH-H = 7.1 Hz, JH-H = 1.9 Hz, 1H), 7.60 (td, JH-H = 7.8 Hz, JH-H
=
ν(cm-1): 3228 (-OH), 1682 (C=O), 1614, 1593, 1577, 1446 (Ar-), 1078
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(C−O). 1H NMR (400 MHz, DMSO) δ: 10.5 (s, -OH), 7.61 (d, JH-H = 8.8 (dd, JH-H = 7.0 Hz, JH-H = 1.9 Hz, 2H), 7.56 (dd, JH-H = 7.8 Hz, JH-H = 1.0
Hz, 1H), 7.43 (t, JH-H = 7.5 Hz, 2H), 7.36 (t, JH-H = 7.2 Hz, 1H), 7.28 (d, Hz, 1H), 7.51 (td, JH-H = 7.2 Hz, JH-H = 1.4 Hz, 1H), 7.32 (d, JH-H = 8.5
JH-H = 6.9 Hz, 2H), 6.83 (dd, JH-H = 8.8 Hz, JH-H = 2.2 Hz, 1H), 6.74 (d, Hz, 1H), 7.21 (td, JH-H = 7.2 Hz, JH-H = 0.6 Hz, 1H), 6.95 (d, JH-H = 8.8
JH-H = 2.2 Hz, 1H), 2.17 (s, 3H). 13C NMR (100 MHz, DMSO) δ: 161.3, Hz, 2H), 3.83 (s, 3H), 3.76 (s, 3H). 13C NMR (100 MHz, CDCl3) δ:
160.7, 154.3, 148.7, 135.3, 130.7 (CH), 128.4 (CH), 128.0 (CH), 127.5 161.6, 159.5, 139.3, 135.7 (CH), 131.9, 130.2 (CH), 129.9 (CH),
(CH), 122.7, 113.4 (CH), 112.8, 102.3 (CH), 16.7 (CH3). MS (ESI) m/z: 129.2, 128.6 (CH), 122.1 (CH), 120.8, 113.9 (CH), 113.6 (CH), 55.3
+
253.2 [M + H]+ (calcd for C16H13O3+ 253.1).
(CH3), 29.9 (CH3). MS (ESI) m/z: 266.2 [M + H]+ (calcd for C17H16NO2
266.1).
7-Amino-4-methyl-3-phenyl-2H-chromen-2-one (3y)
7-Methoxy-1-methyl-3-phenylquinolin-2(1H)-one (5c)
Light yellow solid, mp 281-282 oC (EtOAc) [lit.,28 280-281 C]. IR
o
(KBr) ν(cm-1): 3420 (NH2), 2985 (CH3), 1708 (C=O), 1613, 1445 (Ar-), Light yellow solid, mp 134-135 C. IR (KBr) ν(cm-1): 2979, 2927 (-
1117 (C−O). 1H NMR (400 MHz, DMSO) δ: 7.47 (d, JH-H = 8.7 Hz, 1H), CH3), 1645 (C=O), 1616, 1595, 1508, 1454 (Ar-), 1248, 1211, 1036.
7.42 (t, JH-H = 7.5 Hz, 2H), 7.35 (t, JH-H = 7.3Hz, 1H), 7.25 (d, JH-H = 7.0 1H NMR (400 MHz, CDCl3) δ: 7.70-7.67 (m, 3H), 7.48 (d, JH-H = 8.6 Hz,
Hz, 2H), 6.60 (dd, JH-H = 8.7 Hz, JH-H = 2.0 Hz, 1H), 6.46 (d, JH-H = 2.0 1H), 7.40 (td, JH-H = 7.2 Hz, JH-H = 1.2 Hz, 2H), 7.35-7.31 (m, 1H), 6.81
Hz, 1H), 6.13 (bs, 2H), 2.14 (s, 3H). 13C NMR (100 MHz, DMSO) δ: (dd, JH-H = 8.6 Hz, JH-H = 2.2 Hz, 1H), 6.76 (d, JH-H = 2.2 Hz, 1H), 3.90
161.1, 154.9, 153.2, 149.1, 135.8, 130.9 (CH), 128.4 (CH), 127.7 (s, 3H), 3.72 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 161.8, 161.6,
(CH), 127.2 (CH), 120.1, 111.8 (CH), 109.5, 98.7 (CH), 16.6 (CH3). MS 141.2, 137.0, 136.7 (CH), 130.2 (CH), 129.2, 128.8 (CH), 128.1 (CH),
o
(ESI) m/z: 252.3 [M + H]+ (calcd for C16H14NO2+ 252.1).
127.7 (CH), 114.9, 109.8 (CH), 98.4 (CH), 55.6 (CH3), 29.9 (CH3). HR
MS (ESI) m/z: 266.1179 [M + H]+ (calcd for C17H16NO2+ 266.1176).
3-Acetyl-4-phenyl-2H-chromen-2-one (3z)29
6-Bromo-1-methyl-3-phenylquinolin-2(1H)-one (5d)
o
Colorless solid, mp 141-142 C. IR (KBr) ν(cm-1): 3052, 2982 (-CH3),
1
1728, 1693 (C=O), 1608, 1562, 1448, 1363 (Ar-), 1049 (C−O). H Pale yellow solid, mp 175-176 oC (EtOAc) [lit.,31 176-178 oC]. IR (KBr)
NMR (400 MHz, CDCl3) δ: 7.60-7.56 (m, 1H), 7.52-7.50 (m, 3H), 7.40 ν(cm-1): 2954, 2924 (-CH3), 1647 (C=O), 1579, 1487, 1444, 1415 (Ar-
1
(d, JH-H = 8.3 Hz, 1H), 7.32-7.30 (m, 2H), 7.22 (d, JH-H =4.1 Hz, 1H), ), 1228, 1209, 1118. H NMR (400 MHz, CDCl3) δ: 7.73 (d, JH-H = 2.2
2.24 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 199.0, 158.4, 153.4, Hz, 1H), 7.70-7.67 (m, 3H), 7.63 (dd, JH-H = 8.9 Hz, JH-H = 2.2 Hz, 1H),
151.8, 132.7 (CH), 132.5, 129.6 (CH), 128.8 (CH), 128.5 (CH), 128.1 7.44 (t, JH-H = 7.6 Hz, 2H), 7.40-7.37 (m, 1H), 7.25 (d, JH-H = 6.7 Hz,
(CH), 127.7, 124.6 (CH), 119.4 (CH), 117.0 (CH), 31.1 (CH3). MS (ESI) 1H), 3.77 (s, 3H). 13C NMR (100 MHz, CDCl3) δ: 161.1, 138.5, 136.3,
m/z: 265.1 [M + H]+ (calcd for C17H13O3+ 265.0).
135.3 (CH), 133.7, 132.9 (CH), 130.8 (CH), 128.9 (CH), 128.4 (CH),
128.2 (CH), 122.2, 115.7 (CH), 114.9, 30.1 (CH3). MS (ESI) m/z: 314.1
[M + H]+ (calcd for C16H13BrNO+ 314.0).
3-Isopropyl-2H-chromen-2-one (3zz)
o
o
Colorless solid, mp 47-48 C (EtOAc) [lit.,30 54-55 C]. IR (KBr) ν(cm-
3-Phenylquinolin-2(1H)-one (5e)
1): 2987, 2956, 2871 (-CH3, -CH2), 1707 (C=O), 1610, 1452 (Ar-),
1387, 1190 (C−O). H NMR (400 MHz, CDCl3) δ: 7.47-7.44 (m, 3H), White solid, mp 226-227 oC (EtOAc) [lit.,31 228-230 oC]. IR (KBr)
7.30 (d, JH-H = 8.6 Hz, 1H), 7.25 (t, JH-H = 7.5 Hz, 1H). 13C NMR (100 ν(cm-1): 3428 (-NH), 1635 (C=O), 1610, 1464, 1454 (Ar-), 1120, 1028.
MHz, CDCl3) δ: 161.4, 152.8, 135.9 (CH), 135.7, 130.4 (CH), 127.2 1H NMR (400 MHz, DMSO) δ: 11.96 (s, 1H), 8.10 (s, 1H), 7.77-7.72
(CH), 124.1 (CH), 119.5, 116.3 (CH), 28.7 (CH), 21.4 (CH3). MS (ESI) (m, 3H), 7.50 (td, JH-H = 8.3 Hz, JH-H = 1.2 Hz, 1H), 7.45-7.41 (m, 2H),
1
m/z: 189.1 [M + H]+ (calcd for C12H13O2+ 189.0).
7.40 (d, JH-H = 7.3 Hz, 1H), 7.34 (d, JH-H = 8.1 Hz, 1H), 7.20 (td, JH-H =
7.9 Hz, JH-H = 0.8 Hz, 1H). 13C NMR (100 MHz, DMSO) δ: 161.5, 138.8,
138.0 (CH), 136.7, 131.9, 130.6 (CH), 129.1 (CH), 128.6 (CH), 128.4
(CH), 128.3 (CH), 122.3 (CH), 120.0, 115.1 (CH). MS (ESI) m/z: 222.3
[M + H]+ (calcd for C15H12NO+ 222.1).
1-Methyl-3-phenylquinolin-2(1H)-one (5a)
White solid, mp 134-135 oC (EtOAc) [lit.,31 135-137 oC]. IR (KBr)
ν(cm-1): 3049, 3032 (-CH3), 1645 (C=O), 1591, 1454 (Ar-). H NMR
1
(400 MHz, CDCl3) δ: 7.77 (s, 1H), 7.70 (dd, JH-H = 7.0 Hz, JH-H = 1.4 Hz,
2H), 7.59-7.25 (m, 2H), 7.42 (t, JH-H = 7.5 Hz, 2H), 7.35 (t, JH-H = 8.4
Hz, 2H), 7.22 (t, JH-H = 7.3 Hz, 1H), 3.77 (s, 3H). 13C NMR (100 MHz,
CDCl3) δ: 161.5, 139.6, 136.8 (CH), 132.4, 130.3 (CH), 128.9 (CH),
128.8 (CH), 128.1 (CH), 128.0 (CH), 122.2 (CH), 120.7, 114.0 (CH),
29.9 (CH3). MS (ESI) m/z: 236.2 [M + H]+ (calcd for C16H14NO+ 236.1).
Acknowledgements
We gratefully acknowledge the National Natural Science
Foundation of China (No. 21302042 and 21172055),
Department of Henan Province Natural Science and
Technology Foundation (No. 142102210410), Natural Science
Foundation in Henan Province Department of Education (No.
14B150053), the Program for Innovative Research Team from
Zhengzhou (No. 131PCXTD605), and Natural Science
Foundation from Technology bureau of Zhengzhou (No.
20130883).
3-(4-Methoxyphenyl)-1-methylquinolin-2(1H)-one (5b)
Pale yellow solid, mp 113-114 oC (EtOAc) [lit.,31 114-116 oC]. IR (KBr)
ν(cm-1): 3032, 2952 (-CH3), 1637 (C=O), 1604, 1598, 1510, 1458 (Ar-
1
), 1246, 1178, 1030. H NMR (400 MHz, CDCl3) δ: 7.73 (s, 1H), 7.67
8 | J. Name., 2013, 00, 1-9
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15 Z. J. She, Y. Shi, Y. M. Huang, Y. Y. Cheng, F. J. Song, J. S. You,
Chem. Commun., 2014, 50, 13914.
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DOI: 10.1039/C6RA04787D
Graphic Abstract
KMnO4/AcOH-mediated C3-selective direct arylation of coumarins with
arylboronic acids
Jin-Wei Yuan,* Liang-Ru Yang, Qiu-Yue Yin, Pu Mao, and Ling-Bo Qu*
School of Chemistry & Chemical Engineering, Henan University of Technology, Zhengzhou 450001,
PR China
An efficient protocol for KMnO4/AcOH-mediated C3-direct radical arylation of coumarins with
arylboronic acids to afford 3-arylcoumarin derivatives is described.