One-pot synthesis of 3-fluoroflavones: Via 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones and selectfluor at room temperature

Article abstract of DOI:10.1039/c8ob00135a

A concise and efficient one-pot strategy to synthesize 3-fluoroflavones was developed. 1-(2-Hydroxyphenyl)-3-phenylpropane-1,3-diones were fluorinated using selectfluor with a small amount of CH₃CN at room temperature, followed by cyclization a

Full text of DOI:10.1039/c8ob00135a

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One-Pot Synthesis of 3-Fluoroflavones via 1-(2-Hydroxyphenyl)-3-
phenylpropane-1,3-diones and Selectfluor at Room Temperature
Rui Wang, Jie Han, Chenchen Li, Jie Zhang, Yong Liang,† Tao Wang, Zunting Zhang*
Key Laboratory of the Ministry of Education for Medicinal Resources and Natural
Pharmaceutical Chemistry, National Engineering Laboratory for Resource Development of
Endangered Crude Drugs in Northwest of China, and School of Chemistry and Chemical
Engineering, Shaanxi Normal University, Xi’an 710119, People’s Republic of China. E-mail:
zhangzunting@sina.com; Fax: (+86)-29-81530727; Tel: (+86)-29-85303940.
A concise and efficient one-pot strategy to synthesize 3-fluoroflavones was developed.
1-(2-Hydroxyphenyl)-3-phenylpropane-1,3-diones were fluorinated using selectfluor with a
small amount of CH3CN at room temperature, followed by the cyclization of dehydration in
the presence of trace amount of conc. H2SO4 to provide 3-fluoroflavones. The desired
3-fluoroflavones analogues were obtained in moderate to excellent yields. The strategy
tolerated a wide range of functional groups and did not need sophisticated instruments or
tedious substrate preparation.
Introduction
Flavones, a ubiquitous structure in numerous natural plants, exist in some fruits or
vegetables that possess a variety of biological activities such as anti-inflammatory,1
antibacterial,2 anticancer,3 antitumor,4 and much more.5, 6 Owing to the tremendous bioactivity,
many flavones have significant impact on the modern pharmaceuticals market. It is well
recognized that flavonoid and its derivatives were commonly used for several diseases, such
8
as arteriosclerosis, diabetes, cancer, Alzheimer’s disease, and Parkinson’s disease.7,
Nowadays, great effort has been made in the synthesis and structural modification of various
flavones to alter their biological properties.9 Various chemical modifications of flavone
analogues also have been developed in our group.10-12
Due to the special properties of F, such as high electronegavitity, relatively small size,

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and very low polarizability, installation of one or more fluorine atoms into the organic
molecules usually improve compounds binding, absorption and transportation,13 which will
affect their biological activities. In recent years, some organic fluorine compounds have been
developed as drugs14, such as Fludrocortisone,15 Ciprofloxacin and Gefitinib16. Fuchigami
group17 attempted to synthesize fluoroflavone derivatives via electrochemical fluorination of
flavone substrates using either Et3N·3HF or Et4NF·4HF supporting electrolyte (Scheme 1,
path a). The relative low yields and poor selectivity were observed from the electrochemical
18
fluorination of flavones. Alternatively, Rozen reported the direct fluorination of flavones
o
analogues employing nitrogen-diluted fluorine along with the presence of ethanol at -78 C
(Scheme 1, path b). The 3-fluoroflavone derivatives were obtained in higher yields. Besides
direct fluorination of flavone substrates, the 3-fluoroflavones could be synthesized from
1,3-diketone analogues via photochemical pathway19 or acid-catalyzed cyclodehydration.20, 21
Irradiation of 2-fluoro-2-chloro-1,3-diketone substrates in ACN with light (λ = 352 nm) gave
3-fluoroflavone analogues in moderate yields (Scheme 1, path c).19 In 2004, Vanotti reported
that
treatment
of
1-(2-hydroxyphenyl)-3-phenylpropane-1,3-dione
in DCM afforded
with
NFSI
(N-Fluorobenzenesulfonimide)
2-fluoro-1-(2-
hydroxyphenyl)-3-phenylpropane-1,3-dione intermediate in 28% yield. The following
o
cyclization of the intermediate in AcOH at 90 C in presence of conc. H2SO4 delivered
2-(3,4-dimethoxyphenyl)-3-fluoro-7,8-dimethoxy-4H-chromen-4-one in 23% overall yield
(Scheme 1, path d).21 Herein, an efficient one-pot strategy to synthesize 3-fluoroflavones (2)
in high yields was proposed. 3-Fluoroflavones were obtained by stirring
1-(2-hydroxyphenyl)-3- phenylpropane-1,3-diones (1) and selectfluor 3 in a small amount of
CH3CN at room temperature for 15 h, and the following addition of trace amount of conc.
H2SO4 at ambient temperature (Scheme 1). The strategy to synthesize 3-fluoroflavones only
required a small amount of solvent and trace amount of conc. H2SO4. In addition, the
elimination of the necessity for tedious precursor preparation or sophisticated instruments
made this method easily handled and applicable.

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Previous work
O
O
R1
R1
O
O
R1
F
O
R1 = H, Cl, OAc
path b
O
H
R1 = H, Me, Cl
F
R2
path a
49%-95%
20%-62%
65%-76%
O
O
R1
F
O
O
OH
O
O
R2
45%
R1
R2
R1
96%
F
Cl
F
80%
LiClO4
37%
(PhSO2)2NF
DCM, rt
N-Chlorosuccinimide
O
O
OH
O
O
R1
R2
R1
R2
F
R1 = H, OMe, R2 = OMe
R1 = OMe, R2 = OMe
path d
path c
This work
-
BF4
Cl
OH
O
O
R2
O
N
1) 0.15 mL CH3CN, rt, 15 h
2) 50 L H2SO4, rt, 0.5 h
R1
+
R1
F
N
F
-
BF4
R2
O
0.6 mmol
0.5 mmol
R1 = H, Me, OMe, Br, F, OCOPh, NO2
R2 = H, Me, OMe, F, COOEt, CF3
up to 98% yield
Scheme 1 Synthesis of 3-fluoro-2-phenyl-4H-chromen-4-ones
Results and disscussion
Starting material 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-dione (1a) was synthesized
according to the reported literature.12 The initial optimization was proceeded on the basis of
the fluorination of 1,3-diketone analogues in the literature.22 Treatment of 1a (0.5 mmol) with
selectfluor (0.6 mmol) in CH3CN (5 mL) at ambient temperature for overnight gave
fluorination product 4 in 77% yield as a mixture of two isomers (4a/4a', 1:1, Scheme 2).
Refluxing of 4 in acetic acid (5 mL) in the presence of concentrated sulfuric acid (0.5 mL) for
1 h, the corresponding dehydration product 3-fluoro-2-phenyl-4H-chromen-4-one (2a) was
obtained in 85% yield (Scheme 2; 65% overall yield starting from 1a). Analogously, direct

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addition of conc. H2SO4 to the crude reaction mixture of 1a and selectfluor in CH3CN
afforded 2a in 73% yield, withouting isolation of the intermediate 4. Encouraged by this
promising result, by stirring 1a (0.5 mmol), selectfluor (0.6 mmol) and CH3CN (0.2 mL) at
room temperature for 15 h and the following addition of conc. H2SO4 (50 μL) at ambient
temperature for 0.5 h, 2a was obtained in the yield of 84%. This method furnished
3-fluoroflavones (2) in one-pot with high yield at ambient temperature in the presence of a
small amount of solvent and trace amount of acid.
Scheme 2 Synthesis of 3-fluoro-2-phenyl-4H-chromen-4-one 2a
The one-pot fluorination and cyclization were performed at ambient temperature and the
corresponding optimization data was presented in Table 1. At first, the ratio of 1a and
selectfluor 3 was explored. Screening the loading of selectfluor indicated that 1.2 equiv. of 3
was required to produce 2a in maximum yield (Table 1, entries 1-3). Although fluorination of
1a was attempted with various solvents, no product was observed except acetonitrile (Table 1,
entries 2, 4-7). According to the experimental data, 0.15 mL of ACN was required to give 2a
in best yield (Table 1, entries 8-10). The experimental data indicated that conc. H2SO4 was the
only one promoted the formation of 2a. Other acids were less efficient (HCl) or failed (AcOH
or CF3COOH) to facilitate the elimination of water (Table 1, entries 9, 11-13). The loading of
conc. H2SO4 played an important role as well (Table 1, entries 9, 14-16).
Table 1 Optimization of the reaction conditions a
Molar ratios
Entry
Solvent
H+
Yieldb(%)
1a : 3
1 : 1
1
2
CH3CN (0.2 mL)
CH3CN (0.2 mL)
H2SO4 (50 μL)
H2SO4 (50 μL)
70
84
1 : 1.2

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3
1 : 1.4
1 : 1.2
1 : 1.2
1 : 1.2
1 : 1.2
1 : 1.2
1 : 1.2
1 : 1.2
1 : 1.2
1 : 1.2
1 : 1.2
1 : 1.2
1 : 1.2
1 : 1.2
CH3CN (0.2 mL)
EtOH (0.2 mL)
H2SO4 (50 μL)
68
4
H2SO4 (50 μL)
H2SO4 (50 μL)
H2SO4 (50 μL)
H2SO4 (50 μL)
H2SO4 (50 μL)
H2SO4 (50 μL)
H2SO4 (50 μL)
CH3COOH (50 μL)
CF3COOH (50 μL)
HCl (50 μL)
NR
NR
5
DCM (0.2 mL)
6
THF (0.2 mL)
Trace
NR
58
7
DMF (0.2 mL)
8
CH3CN (0.1 mL)
CH3CN (0.15 mL)
CH3CN (0.25 mL)
CH3CN (0.15 mL)
CH3CN (0.15 mL)
CH3CN (0.15 mL)
CH3CN (0.15 mL)
CH3CN (0.15 mL)
CH3CN (0.15 mL)
9
87
10
11
12
13
14
15
16
82
NR
NR
Trace
79
H2SO4 (25 μL)
H2SO4 (40 μL)
H2SO4 (60 μL)
80
82
a The mixture of 1a (0.12 g, 0.5 mmol) and 3 (0.212 g, 0.6 mmol) was stirred with various solvents for
15 h at ambient temperature, followed by the addition of various acids. The resulting mixture was
continuously stirred at room temperature for 0.5 h. b Isolated yield.
With optimized reaction condition determined, the tolerance and generality of various
functional groups were further explored (Table 2). Treatment of 1, bearing various
substituents on the B ring, with 3 under the optimal condition gave corresponding products 2
in good to excellent yields. Generally, substrates bearing an electron-donating group at B ring
gave cyclization products 2 in higher yields comparing to those with electron-withdrawing
groups (2a-2e, 2x-2z). A similar phenomenon was observed for 2f-2i, which possess
additional methyl group at the para-position of A ring. The electron property of substituents
on A ring significantly affected the yields of 2, while less effect was observed for the location
of substituents. As expected, cyclization products 2 were obtained in higher yields when
bearing electron-donating group at either para-, ortho- or meta- position of A ring. It is worth
mentioning that a broad substrate scope and various functional groups tolerance make this
fluorination/cyclization to be wide application.
Table 2 Scope of the reaction a

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-
BF4 Cl
B
R2
OH O
O
O
C
N
R1
1) CH3CN, rt, 15 h
+
A
R1
B
A
2) H2SO4, rt, 0.5 h
F
-
N
BF4
F
R2
O
3
2a-2t, 2w-2z
1a-1t
OMe
F
O
O
O
O
O
O
O
O
F
F
F
F
2b 85%
2c 93%
2a 87%
2d 65%
COOEt
OMe
O
O
O
O
O
F
F
F
F
O
O
O
2h 87%
2f 90%
2g 89%
2e 82%
OMe
F
O
O
O
O
Br
F
Br
F
Br
F
F
O
O
O
O
2i 60%
2j 75%
2l 56%
2k 54%
OMe
F
MeO
O
O
O
O
F
F
F
F
F
O
F
F
O
O
O
2m 60%
2o 73%
2p 96%
2n 78%
OMe
MeO
F
O
O
O
MeO
O
MeO
O
O
O
O
F
F
F
F
O
O
2t 77%
2q 82%
2r 98%
2s 89%
CF3
F
O
O
O
O
O
F
O2N
F
F
F
O
O
O
2z b 69%
2x 64%
2y 50%
2w 78%
a The mixture of 1a (0.5 mmol) and 3 (0.6 mmol) was stirred with anhydrous CH3CN (150 µL) at
ambient temperature for 15 h, after that conc. H2SO4 (50 μL) was added. The resulting mixture was
b
stirred for 0.5 h; Isolated yields. The mixture of 1z (0.5 mmol) and 3 (0.6 mmol) was stirred with
anhydrous CH3CN (150 µL) at 60 °C for 15 h, after that conc. H2SO4 (50 μL) was added. The resulting
mixture was stirred for 0.5 h; Isolated yields.

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Due to the coordination of significant electron-donating effect and directing effect of the
methoxyl group, fluorination/cyclization of 1u under the optimal condition yielded
6-fluoro-5,7-dimethoxy-2-phenyl-4H-chromen-4-one (2u) in 26% along with the
difluorination product 3,6-difluoro-5,7-dimethoxy-2-phenyl-4H-chromen-4-one (2u') in 7%
(Scheme 3). Further investigation indicated that the ratio of 2u/2u' can be easily controlled by
adjusting the molar ratios of 1a/3. The higher loading of 3 was used, the more difluorination
product 2u' was obtained (See experimental section for detail info). Analogously, treatment of
1-(2-hydroxy-6-methoxyphenyl)-3-phenylpropane-1,3-dione (1v) with 3 also provided a
mixture
of
6-fluoro-5-methoxy-2-phenyl-4H-chromen-4-one
(2v,
20%)
and
3,6-difluoro-5-methoxy-2-phenyl-4H-chromen-4-one (2v', 18%).
Scheme 3. Reaction of 1-(2-hydroxy-6-methoxyphenyl)-3-phenylpropane-1,3-diones (1u,
1v) and selectfluor
To demonstrate the utility and robustness of our synthetic protocol, we proceeded to
synthesize 2a in gram scale. 1-(2-Hydroxyphenyl)-3-phenylpropane-1,3-dione (1a, 1.08g, 4.5
mmol) and selectfluor (3, 1.91g, 5.4 mmol) were stirred with anhydrous CH3CN (1.35 mL)
for 15 h at ambient temperature, after which conc. H2SO4 (450 μL) was added. The resulting
mixture was continuously stirred at room temperature for 0.5 h. After purified by the column
chromatography, 2a was afforded in the yield of 80% (0.86g).
1
The structure of 2 was established via H NMR, 13C NMR, HRMS, IR and X-ray
structure of 2v'. The molecular structure of 2v' is presented in Figure 1, and its moiety
includes a chromone ring [A (C4-C9), C (C1-C3, C9, C8, O1) and a benzene ring B
(C10-C15). The dihedral angle of the ring (AC) and ring (B) is 144.9°. The π-π stacking
intetactions is observed in the X-ray structure of 2v', and it is illustrated in SI (Figure 1). The
chromone rings are arranged in an antiparallel fashion, between A and C, C and A. Both of B
ring of two structure of 2v' are also arranged in an antiparallel fashion. In addition, a sheet is

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formed via three hydrogen bonding and shown in SI (Figure 2, the hydrogen bond lengths and
bondangles are summarized in Table 2). The π-π stacking and hydrogen bonding link the
skeletons of 2v' into a three-dimensional structure.
Figure 1 X-ray crystal structure of 2v'
24
Based on the experimental data as well as the literature reports,23,
a plausible
mechanism for the formation of 2a was proposed (Scheme 4). Initially, tautomerization of 1a
gave enol intermediate A, which attacked fluorine cation from selectfluor by the elimination
of HBF4 to give intermediate 4a. Intramolecular cyclization of 4a gave hemiacetal 4a',
followed by the protonation and dehydration, delivering 2a as the target compound.
Scheme 4 Proposed mechanism for the synthesis of 2
Conclusion
In conclusion, a concise and efficient one-pot synthesis of 3-fluoroflavones at ambient
temperature
has
been
demonstrated.
Treatment
of
1-(2-hydroxyphenyl)-3-
phenylpropane-1,3-diones (1) and selectfluor 3 with a small amount of CH3CN at room

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temperature, followed by the addition of trace amount of conc. H2SO4 at ambient temperature,
21
3-fluoroflavones were obtained. Compared with the reported literature,20,
the strategy
delivered 3-fluoroflavones in high to excellent yields with broad range of functional groups
tolerance and avoided the tedious precursor preparation or sophisticated instruments.
Experimental section
General Information.
Unless stated otherwise, all reagents were purchased from commercial suppliers and used
1
without purification. CH3CN was distilled in the presence of CaH2 before use. H NMR and
13C NMR spectra were obtained by Bruker AM 400 or 600 instrument in CDCl3 or DMSO-d6,
using signals for residual protons or carbon atoms of the solvent as the references.
Uncorrected melting points were obtained on X-5 melting point apparatus. IR spectra were
recorded with Nicollet 170SX FT-IR spectrophotometer and high resolution mass
spectrometry (HRMS) was recorded using the electron-spray ionization (ESI) technique.
Thin-layer chromatography (TLC) used silica gel 60 GF254 plates. Flash column
chromatography was undertaken on silica gel (200–300 mesh).
General procedure for synthesis of 3-fluoro-2-phenyl-4H-chromen-4-ones (2a-2t, 2w-2y).
The mixture of 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-dione (1a, 0.5 mmol) and
selectfluor (3, 0.6 mmol) was stirred with anhydrous CH3CN (0.15 mL) for 15 h at ambient
temperature. Concentrated sulphuric acid (50 μL) was added to the mixture and the resulting
mixture was continuously stirred for 0.5 h at room temperature. The mixture was poured into
water and neutralized with NaOH (10%). Solution was extracted with dichloromethane (20
mL ×3). The organic layer was combined and dried over Na2SO4. Volatiles were removed
under the reduced pressure and the oil residue was purified by column chromatography
(petroleum ether / ethyl acetate 25 : 1) to afford the desired product 2a as a white solid in 87%
yield. Analogously, products 2b-2t, 2w-2z were synthesised with the same method.
3-fluoro-2-phenyl-4H-chromen-4-one (2a).
1
Yield: 87%, 104 mg. White soild. m.p. 93.2-94.0 °C. H NMR (400 MHz, CDCl3), δ (ppm)
8.29 (dd, J = 8.0, 1.5 Hz, 1H), 8.05-8.00 (m, 2H), 7.74-7.70 (m, 1H), 7.59-7.53 (m, 4H),

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2
7.46-7.42 (m, 1H); 13C NMR (100 MHz, CDCl3), δ (ppm) 171.1 (d, J = 16.4 Hz), 155.3,
2
1
3
151.0 (d, J = 24 Hz), 146.3 (d, J = 247.3 Hz), 134.2, 131.7, 129.0, 128.9 128.2 (d, J = 7.8
Hz), 126.0 (d, 4J = 3.4 Hz), 125.3, 124.4 (d, 3J = 7.1 Hz), 118.3; 19F NMR (376 MHz, CDCl3),
δ (ppm) -160.66; IR (KBr), ν (cm−1) 3057, 1726, 1608, 1569, 1467, 1245, 1193, 1103, 983,
896, 756, 673, 462; HRMS (ESI): calc. for C15H9FO2 [M+Na]+ 263.0484, found 263.0494.
3-fluoro-2-(p-tolyl)-4H-chromen-4-one (2b).
Yield: 85%, 108 mg. White soild. m.p. 152.5-153.4 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.26 (dd, J = 8.0, 1.2 Hz, 1H), 7.89 (d, J = 8.2 Hz, 2H), 7.72-7.66 (m, 1H), 7.55 (d, J = 8.5 Hz,
1H), 7.42-7.38 (m, 1H), 7.32 (d, J = 8.2 Hz, 2H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3),
2
2
1
δ (ppm) 170.9 (d, J = 16.4 Hz), 155.2, 151.1 (d, J = 23.9 Hz), 146.1 (d, J = 246.3 Hz),
3
4
4
142.3, 134.0, 129.7, 128.1 (d, J = 8.0 Hz), 126.1 (d, J = 5.1Hz), 125.9 (d, J = 3.2 Hz),
125.10, 124.3 (d, 3J = 7.0 Hz), 118.2, 21.7; 19F NMR (376 MHz, CDCl3), δ (ppm) -160.94; IR
(KBr), ν (cm−1) 3028, 2920, 1911, 1647, 1467, 1384, 1242, 1195, 1109, 979, 894, 761, 692,
476; HRMS (ESI): calc. for C16H11FO2 [M+Na]+ 277.0641, found 277.0650.
3-fluoro-2-(4-methoxyphenyl)-4H-chromen-4-one (2c).
Yield: 93%, 126 mg. White soild. m.p. 152.7-153.4 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.25 (d, J = 7.9 Hz, 1H), 7.97 (d, J = 8.9 Hz, 2H), 7.70-7.66 (m, 1H), 7.53 (d, J = 8.5 Hz, 1H),
7.42-7.38 (m, 1H), 7.02 (d, J = 8.9 Hz, 2H), 3.87 (s, 3H); 13C NMR (100 MHz, CDCl3), δ
(ppm) 170.8 (d, 2J = 16.5 Hz), 162.2, 155.1, 151.0 (d, 2J = 23.7 Hz), 145.8 (d, 1J = 244.7 Hz),
133.9, 130.0 (d, 3J = 8.4 Hz), 125.9 (d, 4J = 3.5 Hz), 125.1, 124.3 (d, 3J = 7.0 Hz), 121.2 (d, 4J
= 5.3 Hz), 118.1, 114.4, 55.56; 19F NMR (376 MHz, CDCl3), δ (ppm) -161.77; IR (KBr), ν
(cm−1) 3010, 2983, 2840, 1905, 1652, 1469, 1398, 1267, 1193, 1026, 831, 754, 624, 503;
HRMS (ESI): calc. For C16H11FO3 [M+Na]+ 293.0590, found 293.0603.
3-fluoro-2-(4-fluorophenyl)-4H-chromen-4-one (2d).
1
Yield: 65%, 84 mg. White soild. m.p. 173.7-174.8 °C. H NMR (400 MHz, CDCl3), δ (ppm)
8.27 (dd, J = 8.0, 1.5 Hz, 1H), 8.05-8.00 (m, 2H), 7.74-7.70 (m, 1H), 7.56 (d, J = 8.6 Hz, 1H),
2
7.45-7.41 (m, 1H), 7.26-7.20 (m, 2H); 13C NMR (100 MHz, CDCl3), δ (ppm) 170.9 (d, J =
1
2
1
16.8 Hz), 164.5 (d, J = 252.5 Hz), 155.1, 150.0 (d, J = 23.9 Hz), 146.1 (d, J = 246.2 Hz),
4
3
4
134.2, 130.6-130.5 (m), 126.0 (d, J = 3.2 Hz), 125.3, 125.1 (dd, J = 5.0 Hz, J = 3.6 Hz),
3
2
124.3 (d, J = 7.0 Hz), 118.2, 116.3 (d, J = 21.9 Hz); 19F NMR (376 MHz, CDCl3), δ (ppm)
-106.76, -160.96; IR (KBr), ν (cm−1) 3278, 3074, 2925, 1913, 1649, 1465, 1386, 1240, 1107,
1008, 977, 844, 757, 617, 499; HRMS (ESI): calc. For C15H8F2O2 [M+Na]+ 281.0390, found
281.0399.
ethyl 4-(3-fluoro-4-oxo-4H-chromen-2-yl)benzoate (2e).

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DOI: 10.1039/C8OB00135A
Yield: 82%, 128 mg. White solid. m.p. 125.8-126.5 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.26 (dd, J = 8.1, 1.4 Hz, 1H), 8.19 (d, J = 8.3 Hz, 2H), 8.08 (d, J = 8.4 Hz, 2H), 7.76-7.70 (m,
1H), 7.59 (d, J = 8.7 Hz, 1H), 7.45-7.42 (m, 1H), 4.41 (q, J = 6.9 Hz, 2H), 1.42 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3), δ (ppm) 170.9 (d, 2J = 16.8 Hz), 165.7, 155.2, 149.7 (d, 2J
= 24.0 Hz), 146.7 (d, 1J = 250.2 Hz), 134.4, 133.0, 132.9 (d, 4J = 5.1 Hz), 130.0, 128.1 (d, 3J
4
3
= 8.0 Hz), 126.0 (d, J = 3.5 Hz), 125.4, 124.3 (d, J = 7.3 Hz), 118.3, 61.6, 14.4; 19F NMR
(376 MHz, CDCl3), δ (ppm) -158.75; IR (KBr), ν (cm−1) 3450, 2977, 1652, 1392, 1278, 1191,
1103, 1012, 896, 754, 657; HRMS (ESI): calc. For C18H13FO4 [M+Na]+ 335.696, found
335.0689.
3-fluoro-6-methyl-2-phenyl-4H-chromen-4-one (2f).
Yield: 90%, 116 mg. White soild. m.p. 146.1-146.8 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.05 (s, 1H), 8.01-7.99 (m, 2H), 7.55-7.52 (m, 3H), 7.50-7.49 (m, 1H), 7.46-7.44 (m, 1H),
2
2.45 (s, 3H); 13C NMR (100 MHz, CDCl3), δ (ppm) 171.1 (d, J = 16.6 Hz), 153.5, 150.8 (d,
1
4
2J = 23.9 Hz), 146.3 (d, J = 246.8 Hz), 135.5, 135.3, 131.5, 129.1 (d, J = 5.0 Hz), 129.0,
3
4
3
128.2 (d, J = 7.9 Hz), 125.2 (d, J = 3.5 Hz), 124.0 (d, J = 7.2 Hz), 118.0, 20.97; 19F NMR
(376 MHz, CDCl3), δ (ppm) -161.04; IR (KBr), ν (cm−1) 3278, 3064, 2914, 1801, 1654, 1566,
1481, 1380, 1211, 1164, 923, 765, 680, 543; HRMS (ESI): calc. For C16H11FO2 [M+Na]+
277.0641, found 277.0649.
3-fluoro-6-methyl-2-(p-tolyl)-4H-chromen-4-one (2g).
Yield: 89%, 119 mg. White soild. m.p. 169.8-170.5 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.03 (s, 1H), 7.88 (d, J = 8.2 Hz, 2H), 7.40-7.48 (m, 1H), 7.43 (d, J = 8.6 Hz, 1H), 7.32 (d, J =
8.2 Hz, 2H), 2.44 (s, 3H), 2.42 (s, 3H); 13C NMR (100 MHz, CDCl3), δ (ppm) 171.1 (d, 2J =
16.3 Hz), 153.6, 151.1 (d, 2J = 23.8 Hz), 146.2 (d, 1J = 245.7 Hz), 142.3, 135.4, 135.3, 129.8,
3
4
4
3
128.2 (d, J = 8.0 Hz), 126.3 (d, J = 5.1 Hz), 125.3 (d, J = 3.5 Hz), 124.1 (d, J = 7.2 Hz),
118.1, 21.8, 21.1; IR (KBr), 19F NMR (376 MHz, CDCl3), δ (ppm) -161.29; IR (KBr), ν (cm−1)
3276, 3041, 2918, 1920, 1809, 1649, 1485, 1377, 1213, 1161, 1020, 927, 817, 659, 632, 480;
HRMS (ESI): calc. For C17H13FO2 [M+Na]+ 291.0797, found 291.0807.
3-fluoro-2-(4-methoxyphenyl)-6-methyl-4H-chromen-4-one (2h).
Yield: 87%, 124 mg. White soild. m.p. 151.2-151.9 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.02 (s, 1H), 7.96 (d, J = 8.8 Hz, 2H), 7.48 (d, J = 8.6 Hz, 1H), 7.42 (d, J = 8.6 Hz, 1H), 7.02
(d, J = 8.8 Hz, 2H), 3.87 (s, 3H), 2.44 (s, 3H); 13C NMR (100 MHz, CDCl3), δ (ppm) 170.8 (d,
2
1
2J = 16.3 Hz), 162.1, 153.4, 150.9 (d, J = 23.8 Hz), 145.8 (d, J = 244.2 Hz), 135.2, 153.1,
3
4
3
4
129.9 (d, J = 8.4 Hz), 125.2 (d, J = 3.5 Hz), 124.0 (d, J = 7.0 Hz), 121.3 (d, J = 5.2 Hz),
117.9, 114.4, 55.6, 21.0; 19F NMR (376 MHz, CDCl3), δ (ppm) -162.11; IR (KBr), ν (cm−1)

Organic & Biomolecular Chemistry
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DOI: 10.1039/C8OB00135A
3074, 2572, 2011, 1901, 1649, 1512, 1382, 1267, 1164, 1012, 831, 597, 505; HRMS (ESI):
calc. For C17H13FO3 [M+Na]+ 307.0749, found 307.0756.
3-fluoro-2-(4-fluorophenyl)-6-methyl-4H-chromen-4-one (2i).
1
Yield: 60%, 82 mg. White soild. m.p. 162.8-163.7 °C. H NMR (400 MHz, CDCl3), δ (ppm)
8.03-8.00 (m, 3H), 7.51 (d, J = 8.6 Hz, 1H), 7.44 (d, J = 8.6 Hz, 1H), 7.22 (m, 2H), 2.45 (s,
3H); 13C NMR (100 MHz, CDCl3), δ (ppm) 170.9 (d, 2J = 16.5 Hz), 164.5 (d, 1J = 252.2 Hz),
153.5, 149.8 (d, 2J = 23.8 Hz), 146.1 (d, 1J = 246.5 Hz), 135.5, 135.4, 130.6-130.4 (m), 125.3,
4
2
125.2 (d, J = 3.4 Hz), 124.0 (d, 3J = 7.1 Hz), 117.9, 116.3 (d, J = 21.8 Hz); 19F NMR (376
MHz, CDCl3), δ (ppm) -107.00, -161.30; IR (KBr), ν (cm−1) 3084, 1905, 1664, 1508, 1377,
1234, 1164, 1016, 931, 838, 661, 588, 501; HRMS (ESI): calc. For C16H10F2O2 [M+Na]+
295.0547, found 295.0554.
6-bromo-3-fluoro-2-phenyl-4H-chromen-4-one (2j).
Yield: 75%, 119 mg. White soild. m.p. 181.3-182.4 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.41 (d, J = 2.7 Hz, 1H), 8.01-7.99 (m, 2H), 7.79 (dd, J = 9.0, 2.3 Hz, 1H), 7.58-7.55 (m, 3H),
7.48 (d, J = 9.1 Hz, 1H). 13C NMR (100 MHz, CDCl3), δ (ppm) 169.6 (d, 2J = 16.8 Hz), 153.9,
151.3 (d, 2J = 23.6 Hz), 146.2 (d, 1J = 248.0 Hz), 137.1, 131.8, 129.0, 128.5, 128.4 (d, 4J = 3.7
Hz), 128.1 (d, 3J = 7.6 Hz), 125.6 (d, 3J = 7.4 Hz), 120.1, 118.8; 19F NMR (376 MHz, CDCl3),
δ (ppm) -159.95; IR (KBr), ν (cm−1) 3278, 3091, 1654, 1564, 1458, 1190, 1151, 997, 765, 680,
634, 538; HRMS (ESI): calc. For C15H8BrFO2 [M+Na]+ 340.9589, found 340.9584.
6-bromo-3-fluoro-2-(p-tolyl)-4H-chromen-4-one (2k).
1
Yield: 54%, 90 mg. White soild. m.p. 181.1-181.9 °C. H NMR (400 MHz, CDCl3), δ (ppm)
8.38 (d, J = 2.1 Hz, 1H), 7.88 (d, J = 8.1 Hz, 2H), 7.77 (dd, J = 8.9, 2.1 Hz, 1H), 7.46 (d, J =
2
8.9 Hz, 1H), 7.34 (d, J = 8.1 Hz, 2H). 13C NMR (100 MHz, CDCl3), δ (ppm) 169.7 (d, J =
17.1 Hz), 153.9, 151.6 (d, 2J = 23.8 Hz), 146.1 (d, 1J = 247.2 Hz), 142.7, 137.0, 129.8, 128.5
4
3
3
4
(d, J = 3.4 Hz), 128.1 (d, J = 8.0 Hz), 125.7 (dd, J = 6.0, J = 4.9 Hz), 120.2, 118.7, 21.8;
19F NMR (376 MHz, CDCl3), δ (ppm) -160.23; IR (KBr), ν (cm−1) 3271, 3037, 1938, 1770,
1643, 1465, 1332, 1188, 1126, 999, 831, 671, 630, 476; HRMS (ESI): calc. For C16H10BrFO2
[M+Na]+ 354.9746, found 354.9736.
6-bromo-3-fluoro-2-(4-methoxyphenyl)-4H-chromen-4-one (2l).
1
Yield: 56%, 97 mg. White soild. m.p. 185.3-186.2 °C. H NMR (400 MHz, CDCl3), δ (ppm)
8.38 (d, J = 2.3 Hz, 1H), 7.97 (d, J = 8.9 Hz, 2H), 7.76 (dd, J = 8.9, 2.3 Hz, 1H), 7.44 (d, J =
8.9 Hz, 1H), 7.04 (d, J = 8.9 Hz, 2H), 3.89 (s, 3H). 13C NMR (100 MHz, CDCl3), δ (ppm)
169.5 (d, 2J = 16.9 Hz), 162.5, 153.9, 151.5 (d, 2J = 23.7 Hz), 145.8 (d, 1J = 245.7 Hz), 136.9,
4
130.1 (d, 3J = 8.6 Hz), 128.5 (d, 4J = 3.6 Hz), 125.7 (d, 3J = 7.5 Hz), 120.81 (d, J = 5.2 Hz),
120.1, 118.7, 114.6, 55.6; 19F NMR (376 MHz, CDCl3), δ (ppm) -161.07; IR (KBr), ν (cm−1)

Page 13 of 20
Organic & Biomolecular Chemistry
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DOI: 10.1039/C8OB00135A
3064, 3008, 2837, 2561, 2036, 1922, 1776, 1604, 1512, 1379, 1257, 1155, 1022, 837, 653,
516; HRMS (ESI): calc. For C16H10BrFO3 [M+Na]+ 370.9695, found 370.9690.
3,6-difluoro-2-phenyl-4H-chromen-4-one (2m).
1
Yield: 60%, 77 mg. White soild. m.p. 144.4-144.9 °C. H NMR (400 MHz, CDCl3), δ (ppm)
8.02-8.0 (m, 2H), 7.91 (dd, J = 8.0, 2.8 Hz, 1H), 7.62-7.54 (m, 4H), 7.48-7.42 (m, 1H); 13C
2
1
NMR (100 MHz, CDCl3), δ (ppm) 170.3 (d, J = 17.0 Hz), 159.6 (d, J = 246.0 Hz), 151.5,
2
1
4
151.3 (d, J = 23.9 Hz), 146.0 (d, J = 247.2 Hz), 131.9, 129.1, 128.7 (d, J = 5.1 Hz), 128.2
(d, 3J = 7.7 Hz), 125.7-125.5 (m), 122.6 (d, 2J = 25.5 Hz), 120.5 (d, 3J = 8.2 Hz), 110.8 (dd, 2J
= 24.0 Hz, 4J = 3.7 Hz); 19F NMR (376 MHz, CDCl3), δ (ppm) -114.85, -161.30; IR (KBr), ν
(cm−1) 3448, 3062, 1658, 1481, 1346, 1199, 1164, 825, 786, 686, 509, 468; HRMS (ESI): calc.
For C15H8F2O2 [M+Na]+ 281.0390, found 281.0383.
3,6-difluoro-2-(4-methoxyphenyl)-4H-chromen-4-one (2n).
Yield: 78%, 112 mg. White soild. m.p. 175.8-176.7 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
7.97 (d, J = 8.7 Hz, 2H), 7.90-7.87 (m, 1H), 7.57-7.54 (m, 1H), 7.44-7.39 (m, 1H), 7.03 (d, J
= 8.7 Hz, 2H), 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3), δ (ppm) 170.0 (dd, 2J = 17.6 Hz, 4J
1
= 2 Hz), 162.4, 159.5 (d, J = 246.1 Hz), 151.4 (d, 2J = 23.8 Hz), 151.3 (d, 4J = 1 Hz), 145.5
(d, 1J = 244.5 Hz), 130.0 (d, 3J = 8.2 Hz), 125.6-125.5 (m), 122.2 (d, 2J = 25.5 Hz), 120.9 (d,
3
2
4
3J = 5.3 Hz), 120.3 (d, J = 8.2 Hz), 114.6, 110.8 (dd, J = 24.0 Hz, J = 3.8 Hz), 55.6; 19F
NMR (376 MHz, CDCl3), δ (ppm) -115.20, -162.38; IR (KBr), ν (cm−1) 3450, 3072, 2844,
2578, 1903, 1649, 1479, 1386, 1269, 1195, 1020, 829, 634, 509; HRMS (ESI): calc. For
C16H10F2O3 [M+Na]+ 311.0496, found 311.0492.
3,6-difluoro-2-(4-fluorophenyl)-4H-chromen-4-one (2o).
Yield: 73%, 101 mg. White soild. m.p. 170.1-171.3 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.04-8.00 (m, 2H), 7.90 (dd, J = 8.0, 3.0 Hz, 1H), 7.60-7.56 (m, 1H), 7.47-7.42 (m, 1H),
7.26-7.22 (m, 2H); 13C NMR (100 MHz, CDCl3), δ (ppm) 170.1 (d, 2J = 14.6 Hz), 164.7 (d, 1J
= 253.0 Hz), 159.7 (d, 1J = 246.4 Hz), 151.4, 150.4 (d, 2J = 23.9 Hz), 145.8 (d, 1J = 247.0 Hz),
3
4
4
2
130.6 (t, J = 8.5 Hz), 125.6-125.5 (m), 124.9 (dd, J = 4.8, J = 3.6 Hz), 122.6 (d, J = 25.6
Hz), 120.4 (d, 3J = 8.3 Hz), 116.4 (d, 2J = 21.9 Hz), 110.9 (dd, 4J = 3.7 Hz, 2J = 24.0 Hz); 19F
NMR (376 MHz, CDCl3), δ (ppm) -106.35, -114.66, -161.50; IR (KBr), ν (cm−1) 3091, 1899,
1664, 1512, 1477, 1245, 1164, 1012, 833, 775, 655, 505; HRMS (ESI): calc. For C15H7F3O2
[M+Na]+ 299.0296, found 299.0291.
3-fluoro-7-methoxy-2-phenyl-4H-chromen-4-one (2p).
Yield: 96%, 130 mg. White soild. m.p. 141.2-142.0 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.14 (d, J = 8.9 Hz, 1H), 8.00-7.94 (m, 2H), 7.52-7.53 (m, 3H), 6.96 (dd, J = 8.9, 1.6 Hz, 1H),
2
6.92 (s, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3), δ (ppm) 170.5 (d, J = 17.0 Hz),

Organic & Biomolecular Chemistry
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DOI: 10.1039/C8OB00135A
4
164.6, 157.0, 150.3 (d, 2J = 24.6 Hz), 146.2 (d, 1J = 247.2 Hz), 131.4, 129.0 (d, J = 5.8 Hz),
128.9, 128.0 (d, 3J = 7.7 Hz), 127.2 (d, 4J = 3.4 Hz), 118.1 (d, 3J = 6.7 Hz), 114.9, 100.2, 56.0;
19F NMR (376 MHz, CDCl3), δ (ppm) -161.49; IR (KBr), ν (cm−1) 3076, 2950, 2844, 1920,
1633, 1446, 1259, 1026, 946, 835, 767, 694, 576, 470; HRMS (ESI): calc. For C16H11FO3
[M+Na]+ 293.0590, found 293.0588.
3-fluoro-7-methoxy-2-(p-tolyl)-4H-chromen-4-one (2q).
Yield: 82%, 116 mg. White soild. m.p. 142.1-143.0 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.13 (d, J = 8.9 Hz, 1H), 7.86 (d, J = 8.1 Hz, 2H), 7.31 (d, J = 8.1 Hz, 2H), 6.95 (d, J = 8.9 Hz,
1H), 6.91 (s, 1H), 3.90 (s, 3H), 2.41 (s, 3H); 13C NMR (100 MHz, CDCl3), δ (ppm) 170.4 (d,
2
1
2J = 16.9 Hz), 164.5, 157.0, 150.6 (d, J = 24.4 Hz), 146.0 (d, J = 246.3 Hz), 142.0, 129.7,
3
4
4
3
127.9 (d, J = 8.0 Hz), 127.2 (d, J = 3.4 Hz), 126.2 (d, J = 5.2 Hz), 118.1 (d, J = 6.9 Hz),
114.8, 100.2, 56.0, 21.7; 19F NMR (376 MHz, CDCl3), δ (ppm) -161.81; IR (KBr), ν (cm−1)
3274, 3043, 2960, 2727, 2617, 1973, 1834, 1608, 1438, 1201, 1020, 877, 819, 767, 688, 603,
482; HRMS (ESI): calc. For C17H13FO3 [M+Na]+ 307.0746, found 307.0756.
3-fluoro-7-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one (2r).
Yield: 98%, 147 mg. White soild. m.p. 180.0-181.1 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.12 (d, J = 8.9 Hz, 1H), 7.93 (d, J = 8.9 Hz, 2H), 7.01 (d, J = 8.9 Hz, 2H), 6.94 (dd, J = 8.9,
2.0 Hz, 1H), 6.89 (d, J = 2.0 Hz, 1H), 3.90 (s, 3H), 3.87 (s, 3H); 13C NMR (100 MHz, CDCl3),
2
2
1
δ (ppm) 170.3 (d, J = 16.8 Hz), 164.4, 162.0, 156.9, 150.5 (d, J = 24.3 Hz), 145.7 (d, J =
244.7 Hz) 129.8 (d, 3J = 8.3 Hz), 127.1 (d, 4J = 3.5 Hz), 121.3 (d, 4J = 5.4 Hz), 118.0 (d, 3J =
6.7 Hz), 114.7, 114.4, 100.2, 56.0, 55.6; 19F NMR (376 MHz, CDCl3), δ (ppm) -162.68; IR
(KBr), ν (cm−1) 3068, 3010, 2842, 2574, 2054, 1924, 1608, 1444, 1394, 1265, 1182, 1026,
829, 607, 501; HRMS (ESI): calc. For C17H13FO4 [M+Na]+ 323.0696, found 323.0708
3-fluoro-2-(4-fluorophenyl)-7-methoxy-4H-chromen-4-one (2s).
Yield: 89%, 128 mg. White soild. m.p. 174.6-175.4 °C. 1H NMR (400 MHz, CDCl3), δ (ppm)
8.13 (d, J = 8.9 Hz, 1H), 8.00-7.97 (m, 2H), 7.23-7.19 (m, 2H), 6.96 (d, J = 8.9 Hz, 1H), 6.91
2
(s, 1H), 3.91 (s, 3H); 13C NMR (100 MHz, CDCl3), δ (ppm) 170.3 (d, J = 17.0 Hz), 164.6,
164.4 (d, 1J = 250.0 Hz), 156.9, 149.4 (d, 2J = 24.4 Hz), 146.0 (d, 1J = 247.4 Hz), 130.4-130.2
(m), 127.2 (d, 4J = 3.4 Hz), 125.2 (dd, 4J = 3.3 Hz, 3J = 5.0 Hz), 118.0 (d, 3J = 6.8 Hz), 116.2
(d, 2J = 21.9 Hz), 115.0, 100.2, 56.0; 19F NMR (376 MHz, CDCl3), δ (ppm) -107.20, -161.79;
IR (KBr), ν (cm−1) 3271, 3074, 3018, 2839, 2621, 2032, 1913, 1612, 1504, 1390, 1238, 1103,
1014, 840, 688, 607, 503; HRMS (ESI): calc. For C16H10F2O3 [M+Na]+ 311.0496, found
311.0488.
3-fluoro-7-Benzoyloxy-2-phenyl-4H-chromen-4-one (2t).

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Organic & Biomolecular Chemistry
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DOI: 10.1039/C8OB00135A
Yield: 77%, 139 mg. White soild. m.p. 159.4-160.2 °C. 1H NMR (400 MHz, CDCl3) δ (ppm)
8.36 (d, J = 8.8 Hz, 1H), 8.22 (d, J = 8.0 Hz, 2H), 8.02 (dd, J = 6.8, 3.2 Hz, 2H), 7.71-7.67 (m,
1H), 7.59-7.53 (m, 6H), 7.33 (dd, J = 8.9, 2.0 Hz, 1H); 13C NMR (100 MHz, CDCl3) δ (ppm)
170.5 (d, 2J = 17.1 Hz), 164.4, 155.8, 155.4, 151.3 (d, 2J = 24.5 Hz), 146.4 (d, 1J = 248.0 Hz),
134.4, 131.8, 130.5, 129.1, 128.9, 128.8, 128.7, 128.2 (d, 3J = 7.8 Hz), 127.5 (d, 4J = 3.5 Hz),
122.2 (d, 3J = 7.3 Hz), 119.8, 111.4; 19F NMR (376 MHz, CDCl3), δ (ppm) -160.59; IR (KBr),
ν (cm−1) 3463, 3070, 1909, 1743, 1614, 1448, 1230, 1168, 1051, 906, 696, 470; HRMS (ESI):
calc. For C22H13FO4 [M+Na]+ 383.0696, found 383.0686.
3-fluoro-8-methyl-2-phenyl-4H-chromen-4-one (2w).
1
Yield: 78%, 99 mg. White soild. m.p. 164.0-164.9 °C. H NMR (400 MHz, CDCl3), δ (ppm)
8.12 (d, J = 8.0 Hz, 1H), 8.07-8.01 (m, 2H), 7.59-7.53 (m, 4H), 7.32 (t, J = 7.6 Hz, 1H), 2.60
2
2
(s, 3H); 13C NMR (100 MHz, CDCl3), δ (ppm) 171.4 (d, J = 16.2 Hz), 153.8, 150.4 (d, J =
4
23.9 Hz), 146.4 (d, 1J = 247.5 Hz), 135.0, 131.6, 129.3 (d, J = 5.1 Hz), 129.1, 128.1 (d, 3J =
8.0 Hz), 127.8, 125.0, 124.3 (d, 3J = 7.0 Hz), 123.7 (d, 4J = 3.5 Hz), 15.9; 19F NMR (376 MHz,
CDCl3), δ (ppm) -160.99; IR (KBr), ν (cm−1) 2885, 1514, 1365, 1251, 1120, 1012, 902, 707;
HRMS (ESI): calc. For C16H11FO2 [M+Na]+ 277.0635, found 277.0632.
3-fluoro-2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one (2x).
1
Yield: 64%, 98 mg. White soild. m.p. 169.6-170.3 °C. H NMR (400 MHz, CDCl3), δ (ppm)
8.30 (d, J = 8.2 Hz, 1H), 8.15 (d, J = 8.3 Hz, 2H), 7.82 (d, J = 8.0 Hz, 2H), 7.78-7.74 (m, 1H),
7.60 (d, J = 8.3 Hz, 1H), 7.49-7.45 (m, 1H); 13C NMR (100 MHz, CDCl3), δ (ppm) 171.0 (d,
2
1
2
2J = 16.8 Hz), 155.3, 149.2 (d, J = 24.2 Hz), 146.8 (d, J = 250.5 Hz), 134.6, 133.2 (q, J =
33.0 Hz), 132.4 (d, 4J = 5.6 Hz), 128.6 (d, 3J = 8.1 Hz), 126.2 (d, 4J = 3.3 Hz), 126.0 (q, 3J =
3
1
3.6 Hz), 125.6, 124.4 (d, J = 7.1 Hz), 123.7 (q, J = 270.8 Hz), 118.3; 19F NMR (376 MHz,
CDCl3), δ (ppm) -63.13, -159.15; IR (KBr), ν (cm−1) 2920, 1498, 1448, 1269, 1091, 1035, 919,
811, 719, 470; HRMS (ESI): calc. For C16H8F4O2 [M+Na]+ 331.0352, found 331.0350.
3-fluoro-2-(2-fluorophenyl)-4H-chromen-4-one (2y).
1
Yield: 50%, 65 mg. White soild. m.p. 110.7-111.5 °C. H NMR (400 MHz, CDCl3), δ (ppm)
8.34 (d, J = 7.9 Hz, 1H), 7.77-7.69 (m, 2H), 7.62-7.55 (m, 2H), 7.48 (t, J = 7.6 Hz, 1H), 7.36
(t, J = 7.6 Hz, 1H), 7.30-7.28 (m, 1H); 13C NMR (100 MHz, CDCl3), δ (ppm) 170.8 (d, 2J =
1
2
1
16.6 Hz), 160.1 (d, J = 254.4 Hz), 155.8, 148.4 (d, J = 29.8 Hz), 146.4 (d, J = 249.2 Hz),
134.3, 133.5 (d, 3J = 8.3 Hz), 130.6-130.5 (m), 126.2 (d, 4J = 3.1 Hz), 125.4, 124.6 (d, 3J = 7.5
4
4
2
Hz), 124.5 (d, J = 3.7 Hz), 118.5, 117.1 (d, J = 3.6 Hz), 116.9 (d, J = 21.2 Hz); 19F NMR
(376 MHz, CDCl3), δ (ppm) -109.74 (d, J = 24.32 Hz), -157.81 (d, J = 24.18 Hz); IR (KBr), ν
(cm−1) 2875, 2767, 1508, 1425, 1305, 1217, 1172, 1126, 919, 711, 657; HRMS (ESI): calc.
For C15H8F2O2 [M+Na]+ 281.0390, found 311.0488.

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DOI: 10.1039/C8OB00135A
3-fluoro-6-nitro-2-phenyl-4H-chromen-4-one (2z).
1
Yield: 69%, 98 mg. White soild. m.p. 183.3-184.4 °C. H NMR (400 MHz, CDCl3), δ (ppm)
9.16 ( d, J = 1.8 Hz 1H), 8.56 (dd, J = 9.1, 2.6 Hz, 1H), 8.06-8.02 (m, 2H), 7.76 (d, J = 9.0 Hz,
1H), 7.61-7.57 (m, 3H); 13C NMR (100 MHz, CDCl3), δ (ppm) 169.7 (d, 2J = 17.8 Hz), 157.9,
151.9 (d, 2J = 24.0 Hz), 146.3 (d, 1J = 250.6 Hz), 144.9, 132.4, 129.3, 128.5, 128.3 (d, 3J = 7.7
4
3
4
Hz), 128.0 (d, J = 4.9 Hz), 124.5 (d, J = 7.7 Hz), 122.8 (d, J = 3.1 Hz), 120.1; 19F NMR
(376 MHz, CDCl3), δ (ppm) -159.0; IR (KBr), ν (cm−1) 3078, 2891, 2767, 1749, 1417, 1288,
1172, 950, 871, 526; HRMS (ESI): calc. For C15H8FNO4 [M+Na]+ 308.0335, found 311.0488.
Synthesis of 2u, 2u' and 2v, 2v'.
The mixture of 1-(2-hydroxyphenyl)-3-phenylpropane-1,3-dione (1u, 0.5 mmol) and
selectfluor (3, 0.6 mmol) was stirred with anhydrous CH3CN (0.15 mL) for 15 h at ambient
temperature. Then the concentrated sulphuric acid (50 μL) was added to the mixture and the
resulting mixture was continuously stirred for 0.5 h at room temperature. The mixture was
poured into water and neutralized with NaOH (10%). Solution was extracted with
dichloromethane (20 mL ×3). The organic layer was combined and dried over Na2SO4.
Volatiles were removed under the reduced pressure and the oil residue was purified by column
chromatography to afford 2u in 26%, 2u' in 7%. When the scale of 1u : 3 molar ratio = 1 : 1.8,
the yield of 2u was 20%, and 2u' was 11%, while the scale of 1u : 3 molar ratio = 1 : 2.4, the
yield of 2u was 6%, 2u' was 17%.
Similarly, 2v, 2v' were prepared with the same method. When the scale of 1v : 3 molar
ratio = 1 : 1.2, the yield of 2v was 20%, and 2v' was 18%, and the scale of 1v : 3 molar ratio
= 1 : 1.8, the yield of 2v was 6%, and 2v' was 39%, while the scale of 1v : 3 molar ratio = 1 :
2.4, 2v was nearly invisible, the yield of 2v' was 46%.
6-fluoro-5,7-dimethoxy-2-phenyl-4H-chromen-4-one (2u).
1
Yield: 26%, 39 mg. White soild. m.p. 166.6-167.4 °C. H NMR (400 MHz, CDCl3) δ (ppm)
7.86-7.84 (m, 2H), 7.54-7.47 (m, 3H), 6.82 (d, J = 6.7 Hz, 1H), 6.65 (s, 1H), 4.05 (s, 3H),
3.99 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 177.1(d, 4J = 2.6 Hz), 161.5, 154.1 (d, 4J =
2.8 Hz), 153.1 (d, 2J = 11 Hz), 147.1 (d, 3J = 9.9 Hz), 143.6 (d, 1J = 243.8 Hz), 131.5, 131.4,
4
129.1, 126.1, 112.8, 108.5, 96.6, 62.8 (d, J = 4.4 Hz), 56.7; 19F NMR (376 MHz, CDCl3), δ
(ppm) -156.34; IR (KBr), ν (cm−1) 3450, 3057, 2935, 2833, 1832, 1639, 1461, 1353, 1199 ,
1124, 875, 771, 690, 553, 470; HRMS (ESI): calc. For C17H13FO4 [M+Na]+ 323.0696, found
323.0692.
3,6-difluoro-5,7-dimethoxy-2-phenyl-4H-chromen-4-one (2u').
1
Yield: 7%, 11 mg. White soild. m.p. 176.7-177.7 °C. H NMR (400 MHz, CDCl3) δ (ppm)
7.98-7.95 (m, 2H), 7.55-7.53 (m, 3H), 6.81 (d, J = 6.6 Hz, 1H), 4.08 (s, 3H), 4.00 (s, 3H); 13C

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DOI: 10.1039/C8OB00135A
2
4
2
NMR (100 MHz, CDCl3) δ (ppm) 169.5 (dd, J = 17.7 Hz, J = 3.1 Hz), 153.6 (d, J = 11.4
Hz), 153.1 (d, 4J = 2.7 Hz), 148.9 (d, 2J = 24.8 Hz), 147.1 (dd, 2J = 10 Hz, 4J = 2.7 Hz), 146.0
(d, 1J = 241.4 Hz), 143.6 (d, 1J = 242.2 Hz), 131.5, 129.0, 128.7 (d, 4J = 5.4 Hz),127.9 (d, 3J =
7.4 Hz), 112.9 (d, 3J = 6.2 Hz), 96.5, 62.9 (d, 4J = 4.5 Hz), 56.8; 19F NMR (376 MHz, CDCl3),
δ (ppm) -156.23, -162.06; IR (KBr), ν (cm−1) 3419, 1737, 1639, 1396, 1166, 1078, 1028, 771,
694; HRMS (ESI): calc. For C17H12F2O4 [M+Na]+ 341.0601, found 341.0599.
6-fluoro-5-methoxy-2-phenyl-4H-chromen-4-one (2v).
1
Yield: 20%, 27 mg. White soild. m.p. 142.1-143.0 °C. H NMR (400 MHz, CDCl3) δ (ppm)
7.91-7.88 (m, 2H), 7.57-7.50 (m, 3H), 7.46-7.42 (m, 1H), 7.30-7.27 (m, 1H), 6.72 (s, 1H),
4.07 (s, 3H); 13C NMR (100 MHz, CDCl3) δ (ppm) 177.7 (d, 4J = 2.9 Hz), 162.1, 153.6 (d, 4J
= 1.8 Hz), 152.5 (d, 1J = 244.1 Hz), 146.6 (d, 2J = 12.3 Hz), 131.8, 131.5, 129.2, 126.3, 121.8
2
3
4
(d, J = 22.6 Hz), 119.6, 113.7 (d, J = 7.3 Hz), 108.3, 62.8 (d, J = 4.4 Hz), 56.8; 19F NMR
(376 MHz, CDCl3), δ (ppm) -133.99; IR (KBr), ν (cm−1) 3421, 3064, 1658, 1415, 1276, 1028,
919, 808, 765, 682, 543; HRMS (ESI): calc. For C16H11FO3 [M+Na]+ 293.0590, found
293.0585.
3,6-difluoro-5-methoxy-2-phenyl-4H-chromen-4-one (2v').
1
Yield: 18%, 26 mg. White soild. m.p. 173.8-174.2 °C. H NMR (400 MHz, CDCl3) δ (ppm)
7.98-7.96 (m, 2H), 7.55-7.52 (m, 3H), 7.48-7.43 (m, 1H), 7.29-7.26 (m, 1H), 4.08 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ (ppm) 170.0 (dd, 2J = 17.6 Hz, 4J = 2.9 Hz), 152.4 (d, 4J = 2.0 Hz),
152.2 (d, 1J = 244.3 Hz), 149.4 (d, 2J = 24.7 Hz), 146.6 (dd, 2J = 12.4 Hz, 4J = 2.6 Hz), 146.0
(d, 1J = 244.7 Hz), 131.7, 129.0, 128.6 (d, 4J = 5.2 Hz), 128.0 (d, 3J = 7.6 Hz), 122.4 (d, 2J =
22.9 Hz), 119.7 (dd, 3J = 6.3 Hz, 3J = 2.1 Hz), 113.7 (d, 3J = 7.8 Hz), 62.8 (d, 4J = 4.4 Hz); 19F
NMR (376 MHz, CDCl3), δ (ppm) -134.27, 161.89; IR (KBr), ν (cm−1) 3450, 3026, 2935,
1922, 1641, 1477, 1230, 1159, 1058, 813, 688, 501; HRMS (ESI): calc. For C16H10F2O3
[M+Na]+ 311.0496, found 311.0493.
Synthesis of 2-fluoro-1-(2-hydroxyphenyl)-3-phenylpropane-1,3-dione (4).
Treatment of 1-(2-Hydroxyphenyl)-3-phenylpropane-1,3-diones 1a (0.5 mmol) and
selectfluor 3 (0.6 mmol) with CH3CN (0.2 mL) as additive at room temperature for 15 h. The
mixture was purified by column chromatography to give fluorination product 4 in 77% yield
as a mixture of two isomers (4a/4a', 1:1). Yield: 77%, 99 mg. Characteristic: a yellow oil as a
1
1:1 mixture of 4a/4a'. H NMR (400 MHz, CDCl3), δ (ppm) 11.53 (s, 1H*), 8.09 (d, J = 8.3
Hz, 1H* and 1H), 8.02-7.98 (m, 1H*), 7.95-7.92 (m, 1H), 7.83-7.74 (m, 1H* and 1H),
7.66-7.56 (m, 1H* and 1H), 7.54-7.46 (m, 3H* and 3H), 7.17-7.08 (m, 1H* and 1H),
7.00-6.93 (m, 1H* and 1H), 6.52 (d, J = 48.8 Hz, 1H*), [5.28 (d, J = 46.4 Hz, 0.70H) 4.72 (d,
J = 47.4 Hz, 0.24H)], [3.62 (s, 0.24H), 3.54 (s, 0.63H)]; 13C NMR (100 MHz, CDCl3), δ (ppm)

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DOI: 10.1039/C8OB00135A
195.5* (d, 2J = 18.9 Hz), 193.5* (d, 2J = 20.3 Hz), 187.5 (d, 2J = 16.5 Hz), 186.5 (d, 2J = 17.3
Hz), 163.5*, 157.7, 157.2, 138.2 (d, 4J = 1.0 Hz), 138.1*, 138.0, 137.7, 137.1, 136.9, 134.9*,
4
3
4
133.6 (d, J = 2.2 Hz), 131.4 (d, J = 5.8 Hz), 130.1, 129.9* (d, J = 3.7 Hz), 129.0*, 128.8,
4
4
4
128.7, 127.6, 127.0 (d, J = 2.1 Hz), 126.4 (d, J = 1.4 Hz), 126.3* (d, J = 1.2 Hz), 122.9*,
4
4
122.7, 120.3 (d, J = 1.0 Hz), 119.7*, 119.0, 118.8*, 118.6, 118.5, 117.4 (d, J = 1.4 Hz),
102.7 (d, 2J = 19.4 Hz), 101.0 (d, 2J = 24.0 Hz), 95.5* (d, 1J = 197.9 Hz), 91.8 (d, 1J = 201.6
Hz), 88.5 (d, 1J = 184.9 Hz); * = 4a; IR (KBr), ν (cm−1) 3479, 1629, 1510, 1373, 1190, 1058,
891, 786, 621; HRMS (ESI): calc. for C15H11FO3 [M+Na]+ 281.0590, found 281.0589.
Conflicts of interest
There are no conflicts to declare.
Acknowledgements
We are grateful for financial support from the National Natural Science Foundation of
China (No: 21672132, 21502110) and the Fundamental Funds Research for the Central
Universities (No: GK201503034).
Present address:
†Department of Molecular Medicine, Beckman Research Institute of City of Hope, Duarte,
California 91010, United States.
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Graphical abstract:
One-Pot Synthesis of 3-Fluoroflavones via 1-(2-Hydroxyphenyl)-3-
phenylpropane-1,3-diones and Selectfluor at Room Temperature
Rui Wang, Jie Han, Chenchen Li, Jie Zhang, Yong Liang,† Tao Wang, Zunting Zhang*
An efficient one-pot synthesis of 3-fluoroflavones by the fluorination of
1-(2-hydroxyphenyl)-3-phenylpropane-1,3-diones with selectfluor and followed by the
cyclization and dehydration in the presence of trace amount of conc. H2SO4 at room temperature
was developed.