Microwave-assisted efficient synthesis of 2-hydroxydeoxybenzoins from the alkali degradation of readily prepared 3-aryl-4-.hydroxycoumarins in water

Article abstract of DOI:10.1248/cpb.c13-00604

This paper describes an operationally simple, green and efficient approach for the synthesis of 2-hydroxydeoxybenzoins bearing diverse substituents from the microwave-assisted alkali degradation of 3-aryl- 4-hydroxycoumarins in water. The latter compounds

Full text of DOI:10.1248/cpb.c13-00604

1166
Regular Article
Chem. Pharm. Bull. 61(11) 1166–1172 (2013)
Vol. 61, No. 11
Microwave-Assisted Efficient Synthesis of 2-Hydroxydeoxybenzoins from
the Alkali Degradation of Readily Prepared 3-Aryl-4-hydroxycoumarins
in Water
Zhong-Zhen Zhou,# Guang-Hua Yan,# Wen-Hua Chen,* and Xue-Mei Yang*
School of Pharmaceutical Sciences, Southern Medical University; Guangzhou 510515, China.
Received July 31, 2013; accepted August 19, 2013
This paper describes an operationally simple, green and efficient approach for the synthesis of 2-hy-
droxydeoxybenzoins bearing diverse substituents from the microwave-assisted alkali degradation of 3-aryl-
4-hydroxycoumarins in water. The latter compounds were readily prepared from the intramolecular Claisen
condensation reaction of methyl 2-(2-arylacetoxy)benzoates in the presence of Cs2CO3–acetone, in excellent
yields and without laborious workup procedures. This method is highly atom-economic and thus applicable
for the large-scale synthesis of 2-hydroxydeoxybenzoins.
Key words 3-aryl-4-hydroxycoumarin; atom economy; 2-hydroxydeoxybenzoin; microwave irradiation;
water chemistry
2-Hydroxydeoxybenzoins (2-OH-DBOs, Fig. 1) are analogs
of 2-hydroxydihydrochalcones and exhibit multiple pharma-
Results and Discussion
Because methyl 2-(2-arylacetoxy)benzoates 1 are readily
cological activities, including anti-microbial,1–3) anti-oxidant,4) hydrolyzed under reported conditions35–39) and 3-aryl-4-hy-
anti-inflammatory,5) vasodilator6) and estrogenic effects.7–9) droxycoumarins 2 are key intermediates for the synthesis of
2-OH-DBOs are also key precursors for many drugs with 2-OH-DBOs 3, we firstly revisited the intramolecular Claisen
promising pharmacological properties, such as 4-hydroxycou- condensation reaction of methyl 2-(2-phenylacetoxy)benzoate
marins,10) 2,3-diaryl-2H-1-benzopyrans,11) 3-arylflavones,12) 1a in acetone as a model reaction to search for the optimized
Schiff bases,4) benzofurans,13) isoflavones,14,15) biaryl heterocy- reaction conditions. The results are summarized in Table 1.
cles,16) isoquinolin-1(2H)-ones17) and Landomycin A18) (Fig. 1). Initially, we investigated the effect of bases and temperature
In addition, 2-OH-DBOs are used industrially to manufacture (entries 1–9). As a result, compound 2a was prepared in 88%
fire-retardant polymers.19) Therefore, considerable endeavors yield in the presence of Cs2CO3 at room temperature (entry
have been made to develop sophisticated approaches for the 5). However, it was not detected at room temperature in the
synthesis of 2-OH-DBOs.
presence of Na2CO3 (entry 1), K2CO3 (entry 3), or LiOH (entry
Among the various methods to date, classic methods, such 7). Stronger bases, such as KOH (entry 9), led to the complete
as Hoesch reactions,20,21) Nencki reactions22,23) and Friedel– hydrolysis of compound 1a. Because of the hydrolysis of com-
Crafts acylation reactions24,25) of polyphenols with substituted pound 1a, raising the temperature was unfavorable, except in
phenylacetonitriles or phenylacetic acids are attractive for the the presence of K2CO3 (entry 4). In addition, it is reported
ready synthesis of polyhydroxydeoxybenzoins. However, these that 4-hydroxy-3-phenylcoumarins can be prepared from the
methods are only applicable for symmetrical polyphenols, phase transfer catalyst-mediated one-pot reaction of methyl
such as resorcinol, phloroglucinol, benzene-1,2,3-triol, pyro- 2-hydroxybenzoates with arylacetyl chlorides.35,36) Therefore,
catechol and hydroquinone. The yields of 2-OH-DBOs from we also carried out the reaction in the presence of ammonium
asymmetrical phenols are very low (<10%).26)
salts (entries 10–13). Thus, compound 2a was prepared in
An alternative approach for the synthesis of 2-OH-DBOs 47–75% yields in the presence of K2CO3–BnEt3NCl. However,
is the alkali degradation of 3-aryl-4-hydroxycoumarins in it was not detected in the presence of K2CO3–Et4NBr. These
MeOH (only one citation in the Chemical abstracts data- results enabled us to conclude that the optimized condition
base).27) However, the synthetic procedures are tedious and was Cs2CO3–acetone at 20°C. This method avoids the use
time-consuming. It is reported that the alkali decarboxylation of poisonous pyridine.10,37) More importantly, the hydrolysis
of coumarins can be also carried out under other conditions, of methyl 2-(2-arylacetoxy)benzoates 1 was rarely observed
such as dimethyl sulfoxide (DMSO)–H2O,28) H2O/imidazole,29) (except in the synthesis of compound 2j, vide infra), which
microwave-assisted H2O–1-hexyl-3-methylimidazolium bro- readily takes place under the reported conditions, such as
mide,30) (CH2OH)2,28,31) H2O–(CH2OH)2,32) N,N-dimethylform- K2CO3–refluxing acetone,35,36) solvent-free Na at 200°C38) and
amide (DMF)33) and tetrahydrofuran (THF)–allylpalladium lithium bis(trimethylsilyl)amide (LiHMDS) (or NaHMDS)–
chloride dimer.34) Herein we report the first efficient synthesis THF at −20°C.39)
of 2-OH-DBOs 3 from the microwave-assisted alkali degrada-
This condition was applicable for a wide range of methyl
tion of 3-aryl-4-hydroxycoumarins 2 in water, starting from 2-(2-arylacetoxy)benzoates 1 bearing both electron-donating
methyl 2-(2-arylacetoxy) benzoates 1 (Chart 1).
and electron-withdrawing substituents (Table 2). For compari-
son, we also conducted the reactions in the presence of KOH–
pyridine at room temperature, which is a classic method for
the synthesis of 3-aryl-4-hydroxycoumarins 2. It is clear from
Table 2 that, compared with the outcomes (48–60% yields)
under the conditions of KOH–pyridine at room temperature,
The authors declare no conflict of interest.
# These authors contributed equally to this work.
© 2013 The Pharmaceutical Society of Japan
*To whom correspondence should be addressed. e-mail: whchen@smu.edu.cn; xujp@smu.edu.cn

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1167
Fig. 1. Drugs That Are Synthesized from 2-OH-DBOs
Chart 1. Synthetic Route for Compounds 3a–j
the yields of compounds 2 under our optimized condition poor under microwave irradiation (entry 13). Taken together,
(Cs2CO3–acetone at 20°C) increased by 15–37% and reached we concluded that, under microwave irradiation, the opti-
63–94%.
mized conditions were 140°C and 10min in water. Thus, the
With 3-aryl-4-hydroxycoumarins 2 readily available and microwave-assisted alkali degradation of 4-hydroxy-3-phenyl
with the aim to synthesize 2-OH-DBOs 3 bearing various coumarin 2a is characterized not only by the excellent yields
substituents under mild conditions, we carried out the alkali and high efficiency, but also by the environmentally friendly
degradation of 3-aryl-4-hydroxycoumarins 2 under microwave reaction media (water).
irradiation. The degradation of 4-hydroxy-3-phenylcoumarin
Then, we extended these reaction conditions to other
2a was chosen as a model to optimize the effect of solvent, substrates (Table 4). As can be seen from Table 4, moder-
time and temperature. The results are summarized in Table 3. ate to good isolated yields (16–84%) were achieved under
As shown in Table 3, raising the reaction temperature from conventional heating. However, the reactions were sluggish
100 to 140°C improved the yield of compound 3a remark- (180–1368min) and highly dependent on the starting materi-
ably from 21 to 99% yields (entries 1–5). Further increases als. Prolonging the reaction time did not significantly improve
of the temperature above 140°C led to a decrease in the yield the yield. In sharp contrast, under microwave irradiation,
(entries 5–7). This may be due to the increasing instability the reactions were completed in 10–15min and compounds
of compound 3a at high temperatures. On the other hand, 3a–j were isolated in 62 to 99% yields. More importantly, this
the yields increased with time, i.e., from 45% (1min, entry condition was applicable for the synthesis of a wide range of
8) to 99% yields (10min, entry 5). Extending the reaction 2-hydroxydeoxybenzoins bearing both electron-donating and
time longer than 10min did not change the yield significantly electron-withdrawing substituents, except compound 3j be-
(entries 10–12). It should be noted that yield in MeOH was cause of some side reactions.

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Vol. 61, No. 11
Table 1. The Effect of Bases and Temperature on the Yields of 4-Hydroxy-3-phenylcoumarin 2aa)
No.
Base
T (°C)
t (h)
Isolated yield (%)
b)
1
2
3
4
5
6
7
8
9
Na2CO3
Na2CO3
20
5
3
—
Reflux
20
Tracec)
b)
K2CO3
5
—
K2CO3
Reflux
20
5
46
88
55
Cs2CO3
4
Cs2CO3
35
2
b)
LiOH
20
5
—
LiOH
30
1.5
10
5
Tracec)
Tracec)
KOH
20
b)
10
K2CO3+Et4NBr
K2CO3+Et4NBr
K2CO3+BnEt3NCl
K2CO3+BnEt3NCl
20
—
11
12
13
Reflux
20
2
Tracec)
2
75
Reflux
1
47
a) All the reactions were run with compound 1a (1.0mmol), base (5.0mmol) and ammonium salt (1.0mmol in the case of entries 10–13) in anhydrous acetone unless other-
wise noted. b) No reaction was observed. c) Significant hydrolysis of 1a was observed.
Table 2. Synthesis of 3-Aryl-4-hydroxycoumarinsa)
Cs2CO3–Acetone
Isolated yield (%)
KOH–Pyridine
Isolated yield (%)
Compound
R1
R2
t (h)
t (h)
2a
2b
2c
2d
2e
2f
H
H
4′-F
4′-MeO
H
4.0
4.5
7.5
4.5
7.5
7.5
6.0
4.0
6.0
11.0
88
72
78
88
88
94
83
89
89
63
2.0
2.0
2.5
6.0
8.0
6.0
7.5
8.0
5.5
5.5
56
55
48
48
51
57
60
60
60
48
H
H
Me
Me
Me
Me
Me
Me
Me
2′-Cl
4′-F
2′-Cl-4′-F
4′-Cl
4′-MeO
3′,4′-diMeO
2g
2h
2i
2j
a) All the reactions were run with compounds 1 (1.0mmol) and base (5.0mmol) in acetone (3mL) or pyridine (5mL) at room temperature unless otherwise noted.
carbonate/acetone at room temperature is an optimized reac-
Concluding Remarks
In conclusion, we have developed a mild and practical ap- tion condition that boasts of excellent yields, little hydrolysis
proach for the synthesis of 2-hydroxydeoxybenzoins bearing and simple workup procedures.
diverse substituents from the alkali degradation of 3-aryl-
4-hydroxycoumarins in water. This procedure is characterized
Experimental
by excellent yield, high efficacy and easy manipulation, and
General Electrospray ionization (ESI) and high resolu-
thus applicable for the large-scale synthesis of 2-hydroxy- tion-electron ionization (HR-EI) mass spectra were measured
deoxybenzoins. Moreover, it reduces the use of organic on a water ultra performance liquid chromatography (UPLC)/
solvents, minimizes the formation of waste, and improves Quattro Premier XE and Thremo High Resolution mass spec-
1
energy consumption. In addition, we have also revisited trometer (MAT95XP), respectively. H- and 13C-NMR spectra
the intramolecular Claisen condensation reaction of methyl were recorded in CDCl3 or DMSO-d6 using Varian Mercury
2-(2-arylacetoxy)benzoates as key starting materials for the 400 spectrometers and tetramethylsilane (TMS) as an internal
synthesis of 2-hydroxydeoxybenzoins, and found that cesium reference. Microwave-irradiated reactions were carried out

November 2013
1169
Table 3. Optimization of the Model Reaction under Microwave Irradiationa)
No.
Solvent
T (°C)
t (min)
Isolated yield (%)
1
2
3
4
5
6
7
8
9
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
H2O
MeOH
100
110
120
130
140
150
160
140
140
140
140
140
140
10
10
10
10
10
10
10
1
21
51
62
75
99
88
86
45
5
83
10
15
20
25
10
98
11
12
13
95
94
Trace
a) All the reactions were run with compound 2a (1.0mmol) in 10% NaOH solution (5mL) unless otherwise noted.
Table 4. Synthesis of 2-Hydroxydeoxybenzoins 3a–j under the Condition of Microwave Irradiation and Conventional Heating
Microwave irradiationa)
t (min) Isolated yield (%)
10 99
Conventional heatingb)
t (min) Isolated yield (%)
Compound
R1
R2
3a
3b
3c
3d
3e
3f
H
H
4′-F
4′-MeO
H
180
330
360
360
390
552
510
582
690
1368
84
40
72
39
58
81
57
63
56
16
H
10
10
10
10
10
10
10
10
10
82
88
88
84
92
74
89
79
62
H
Me
Me
Me
Me
Me
Me
Me
2′-Cl
4′-F
2′-Cl-4′-F
4′-Cl
4′-MeO
3′,4′-diMeO
3g
3h
3i
3j
a) All the reactions were run with compounds 2 (1.0mmol) in 10% NaOH solution (5mL) at 140°C for 10min unless otherwise noted. b) The reactions were run under
refluxing conditions in 10% NaOH solution (5mL) for compounds 2a–i (1.0mmol), and in a mixture of 10% NaOH and methanol (5mL, 4:1, v/v) for compound 2j (1.0mmol).
on a U.S.A. CEM Discover Focused Microwave Synthesizer filtration and recrystallized from ethanol to give compound 2a
(Serial Number DU8290), in sealed heavy-walled Pyrex tubes. (134mg, 56%).
During the reaction time, single mode microwave irradia-
tion at constant temperature, pressure and irradiation power 4-hydroxycoumarins 2a–j in the Presence of Cs2CO3–Dry
(100W) was achieved by automatic power control. Acetone at Room Temperature 4-Hydroxy-3-phenylcouma-
General Procedures for the Preparation of 3-Aryl-
General Procedures for the Preparation of 3-Aryl-4-hy- rin 2a as an example: to a solution of compound 2a (130mg,
droxycoumarins 2a–j in the Presence of KOH–Pyridine at 0.5mmol) in dry acetone (3mL) was added Cs2CO3 (815mg,
Room Temperature 4-Hydroxy-3-phenylcoumarin 2a as an 2.5mmol). The resulting mixture was stirred at room tem-
example: to a solution of methyl 2-(2-phenylacetoxy) benzoate perature for 4h. Then the reaction solution was poured into
2a (270mg, 1.0mmol) in dry pyridine (5mL) was added KOH cold HCl (3N, 10mL). The formed solid was collected by fil-
(280mg, 5mmol). The resulting mixture was stirred at room tration and re-crystallized from ethanol to give compound 2a
temperature for 2h. Then the reaction solution was poured (210mg, 88%).
into cold HCl (3N, 20mL). The formed solid was collected by
4-Hydroxy-3-phenyl-2H-chromen-2-one (2a)10): 1H-NMR

1170
Vol. 61, No. 11
(400MHz, DMSO-d6) δ: 7.33–7.47 (m, 7H), 7.67 (t, J=7.8Hz, ([M+K]+), 309.9 ([M+Na]+), 287.8 ([M+H]+).
1H), 8.05 (d, J=7.6Hz, 1H), 11.42 (s, 1H, OH). 13C-NMR
4-Hydroxy-3-(4-methoxyphenyl)-8-methyl-2H-chromen-2-
(100MHz, DMSO-d6) δ: 106.55, 116.62, 116.83, 124.22, one (2i)10): 1H-NMR (400MHz, DMSO-d6) δ: 2.39 (s, 3H), 3.80
124.35, 127.87, 128.38, 131.40, 132.47, 132.71, 152.70, 160.68, (s, 3H), 7.00 (d, J=7.6Hz, 2H), 7.28 (d, J=7.6Hz, 1H), 7.33 (d,
162.31. ESI-MS m/z: 277.2 ([M+K]+), 239.2 ([M+H]+).
3-(4-Fluorophenyl)-4-hydroxy-2H-chromen-2-one
J=8.0Hz, 2H), 7.51 (d, J=7.2Hz, 1H), 7.83 (d, J=7.6Hz, 1H),
(2b)10): 11.11 (s, 1H, OH). 13C-NMR (100MHz, DMSO-d6) δ: 15.62,
1H-NMR (400MHz, DMSO-d6) δ: 7.25 (t, J=8.2Hz, 2H), 55.51, 113.95, 116.57, 121.71, 123.76, 124.37, 125.36, 132.57,
7.38–7.46 (m, 4H), 7.67 (t, J=7.8Hz, 1H), 8.01 (d, J=7.6Hz, 133.46, 150.86, 159.04, 160.60, 162.41. ESI-MS m/z: 321.9
1H), 11.45 (s, 1H, OH). 13C-NMR (100MHz, DMSO-d6) δ: ([M+K]+), 283.9 ([M+H]+).
105.59, 115.20, 115.41, 116.65, 116.76, 124.13, 124.40, 128.65,
3-(3,4-Dimethoxyphenyl)-4-hydroxy-8-methyl-2H-chro-
128.68, 132.78, 133.48, 133.56, 152.70, 160.76 (C–F), 160.84, men-2-one (2j)10): 1H-NMR (400MHz, DMSO-d6) δ: 2.39
162.30, 163.18 (C–F). ESI-MS m/z: 279.4 ([M+Na]+), 257.5 (s, 3H), 3.76 (s, 3H), 3.81 (s, 3H), 6.91–7.04 (m, 3H), 7.27 (t,
([M+H]+).
J=7.7Hz, 1H), 7.51 (d, J=7.3Hz, 1H), 7.81 (d, J=7.4Hz, 1H),
4-Hydroxy-3-(4-methoxyphenyl)-2H-chromen-2-one (2c)10): 11.05 (s, 1H, OH). 13C-NMR (100MHz, DMSO-d6) δ: 15.60,
1H-NMR (400MHz, DMSO-d6) δ: 3.80 (s, 3H), 7.00 (d, 55.90, 55.94, 106.12, 112.06, 115.21, 116.53, 121.71, 123.77,
J=8.8Hz, 2H), 7.31–7.43 (m, 4H), 7.67–7.63 (m, 1H), 7.99 (dd, 123.96, 124.50, 125.32, 133.46, 148.73, 148.79, 150.90, 160.59,
J=7.9, 1.2Hz, 1H), 11.20 (s, 1H, OH). 13C-NMR (100MHz, 162.31. ESI-MS m/z: 351.9 ([M+K]+), 335.9 ([M+Na]+), 313.9
DMSO-d6) δ: 55.51, 106.22, 113.95, 116.56, 116.86, 124.03, ([M+H]+).
124.27, 124.33, 132.52, 132.58, 152.58, 159.07, 160.31, 162.46.
General Procedures for the Conventional Preparation of
2-Hydroxydeoxybenzoins 3a–j 2-Hydroxydeoxybenzoin 3a
Negative ESI-MS m/z: 268.0 ([M−H]−).
4-Hydroxy-8-methyl-3-phenyl-2H-chromen-2-one
(2d)10): as an example: to a stirring 10% NaOH solution (5mL) was
1H-NMR (400MHz, CDCl3) δ: 2.50 (s, 3H), 6.47 (s, 1H), 7.22 added compound 2a (238mg, 1.0mmol). The resulting mixture
(t, J=7.6Hz, 1H), 7.43–7.48 (m, 4H), 7.53–7.56 (m, 2H), 7.75 was refluxed for 3h. Then the reaction solution was poured
(d, J=7.6Hz, 1H). 13C-NMR (100MHz, DMSO-d6) δ: 15.63, into cold HCl (6N, 5mL) and extracted with ethyl acetate
106.32, 116.52, 121.77, 123.80, 125.44, 127.87, 128.41, 131.40, (10 mL×3). The combined organic layer was washed with
132.51, 133.64, 150.99, 160.85, 162.24. ESI-MS m/z: 275.6 water (15mL×3), dried over anhydrous MgSO4 and concen-
([M+Na]+), 253.5 ([M+H]+).
trated. The obtained residue was purified by chromatography
3-(2-Chlorophenyl)-4-hydroxy-8-methyl-2H-chromen-2-one on a silica gel column, eluting with petroleum ether to afford
1
(2e): H-NMR (400MHz, DMSO-d6) δ: 2.41 (s, 3H), 7.30 (t, compound 3a (198mg, 84%).
J=7.7Hz, 1H), 7.37–7.46 (m, 3H), 7.56 (d, J=8.0Hz, 2H), 7.87
General Procedures for Microwave-Assisted Preparation
(d, J=8.0Hz, 1H), 11.59 (s, 1H, OH). 13C-NMR (100MHz, of 2-Hydroxydeoxybenzoins 3a–j 2-Hydroxydeoxybenzoin
DMSO-d6) δ: 15.64, 104.03, 116.22, 121.94, 123.93, 125.61, 3a as an example: compound 2a (238mg, 1.0mmol) and
127.55, 129.60, 130.22, 131.68, 133.76, 133.98, 135.07, 151.31, 10% NaOH solution (5mL) were added to a microwave tube.
161.44, 161.79. ESI-MS m/z: 309.8 ([M+Na]+), 287.8 ([M+ After sealed, the tube was microwave-irradiated at 140°C for
H]+). HR-EI-MS for C16H11ClO3 (M+) Calcd: 286.0397; Found: 10min. The reaction solution was poured into cold HCl (6N,
286.0392.
5mL) and extracted with ethyl acetate (10mL×3). The com-
3-(4-Fluorophenyl)-4-hydroxy-8-methyl-2H-chromen-2- bined organic layer was washed with water (15mL×3), dried
one (2f): 1H-NMR (400MHz, DMSO-d6) δ: 2.40 (s, 3H), over anhydrous MgSO4 and concentrated to afford compound
7.23–7.303 (m, 3H), 7.44 (dd, J=8.4, 5.6Hz, 2H), 7.53 (d, 3a (210mg, 99%).
J=7.2Hz, 1H), 7.85 (d, J=8.0Hz, 1H), 11.32 (s, 1H, OH).
1-(2-Hydroxyphenyl)-2-phenylethanone (3a)41): 1H-NMR
13C-NMR (100MHz, DMSO-d6) δ: 15.62, 105.34, 115.21, (400MHz, CDCl3) δ: 4.31 (s, 2H), 6.89–6.93 (m, 1H),
115.42, 116.46, 121.79, 123.83, 125.47, 128.73, 128.76, 133.46, 6.98–7.01 (m, 1H), 7.27–7.30 (m, 3H), 7.34–7.38 (m, 2H),
133.55, 133.72, 150.98, 160.75 (C–F), 161.09, 162.24, 163.17 7.45–7.50 (m, 1H), 7.87 (dd, J=8.2, 1.4Hz, 1H), 12.22 (s, 1H).
(C–F). ESI-MS m/z: 293.8 ([M+Na]+), 271.9 ([M+H]+). HR- 13C-NMR (100MHz, CDCl3) δ: 45.10, 118.63, 118.95, 119.02,
EI-MS for C16H11FO3 (M+) Calcd: 270.0692; Found: 270.0685.
127.16, 128.75, 129.39, 130.38, 133.90, 136.52, 162.89, 203.85.
3-(2-Chloro-4-fluorophenyl)-4-hydroxy-8-methyl-2H-chro- Negative ESI-MS m/z: 211.5 ([M−H]−).
men-2-one (2g): 1H-NMR (400MHz, DMSO-d6) δ: 2.41
2-(4-Fluorophenyl)-1-(2-hydroxyphenyl)ethanone (3b): H-
1
(s, 3H), 7.28–7.33 (m, 2H), 7.45 (t, J=7.4Hz, 1H), 7.56 (t, NMR (400MHz, CDCl3) δ: 4.28 (s, 2H), 6.91 (t, J=7.6Hz,
J=7.4Hz, 2H), 7.83 (d, J=8.0Hz, 1H), 11.61 (s, 1H, OH). 1H), 6.97–7.08 (m, 3H), 7.22–7.25 (m, 2H), 7.48 (t, J=7.8Hz,
13C-NMR (100MHz, DMSO-d6) δ: 15.62, 103.01, 114.77, 1H), 7.84 (d, J=8.0Hz, 1H), 12.15 (s, 1H). 13C-NMR
114.98, 116.17, 116.82, 117.07, 121.91, 123.99, 125.63, 128.13, (100MHz, CDCl3) δ: 44.10, 115.51, 115.72, 118.70, 118.89,
128.16, 134.07, 135.16, 135.25, 136.07, 136.18, 151.34, 161.09 119.01, 129.45, 129.49, 130.15, 130.96, 131.04, 136.64, 160.78
(C–F), 161.44, 162.09, 163.55 (C–F). ESI MS m/z: 327.5 ([M+ (C–F), 162.85, 163.22 (C–F), 203.53. Negative ESI-MS m/z:
Na]+), 305.5 ([M+H]+). HR-EI-MS for C16H10ClFO3 (M+) 229.6 ([M−H]−). HR-EI-MS for C14H11FO2 (M+) Calcd:
Calcd: 304.0303; Found: 304.0291.
230.0743; Found: 230.0733.
3-(4-Chlorophenyl)-4-hydroxy-8-methyl-2H-chromen-2-one
1-(2-Hydroxyphenyl)-2-(4-methoxyphenyl)ethanone
(3c):
(2h)40): H-NMR (400MHz, DMSO-d6) δ: 2.40 (s, 3H), 7.28 1H-NMR (400MHz, CDCl3) δ: 4.31 (s, 2H), 6.88–6.98
(t, J=7.4Hz, 1H), 7.42–7.55 (m, 5H), 7.85 (d, J=8.0Hz, 1H), (m, 3H), 6.98–7.00 (m, 1H), 7.19 (dd, J=6.8, 2.0Hz, 2H),
11.43 (s, 1H, OH). 13C NMR (100MHz, DMSO-d6) δ: 15.62, 7.45–7.49 (m, 1H), 7.87 (dd, J=8.2, 1.4Hz, 1H), 12.23 (s, 1H).
105.12, 116.44, 121.83, 123.87, 125.51, 128.45, 131.49, 132.53, 13C-NMR (100MHz, CDCl3) δ: 44.21, 55.21, 114.21, 118.61,
133.31, 133.83, 151.02, 161.25, 162.07. ESI-MS m/z: 325.8 118.91, 118.97, 125.78, 130.32, 130.41, 136.44, 158.72, 162.87,
1

November 2013
1171
204.16. Negative ESI-MS m/z: 241.6 ([M−H]−). HR-EI-MS for HR-EI-MS for C17H18O4 (M+) Calcd: 286.1205; Found:
C15H14O3 (M+) Calcd: 242.0943; Found: 242.0938.
1-(2-Hydroxy-3-methylphenyl)-2-phenylethanone
286.1200.
(3d)26):
1H-NMR (400MHz, CDCl3) δ: 2.26 (s, 3H), 4.31 (s, 2H), 6.81
Acknowledgment This work was financially supported
(t, J=7.8Hz, 1H), 7.27–7.30 (m, 3H), 7.34–7.38 (m, 3H), 7.73 by the National Natural Science Foundation of China (No.
(dd, J=8.0, 1.2Hz, 1H), 12.54 (s, 1H). 13C-NMR (100MHz, 21002048).
CDCl3) δ: 15.47, 45.15, 118.24, 118.28, 127.09, 127.69, 127.94,
128.71, 129.38, 134.11, 137.20, 161.38, 204.05. Negative ESI-
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(3e): H-NMR (400MHz, CDCl3) δ: 2.27 (s, 3H), 4.48 (s, 2H),
6.85 (t, J=7.6Hz, 1H), 7.20–7.25 (m, 3H), 7.36–7.38 (m, 1H),
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2-(4-Fluorophenyl)-1-(2-hydroxy-3-methylphenyl)ethanone
1
(3f): H-NMR (400MHz, CDCl3) δ: 2.26 (s, 3H), 4.28 (s, 2H),
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ESI-MS m/z: 283.0 ([M+K]+), 267.5 ([M+Na]+), 245.4 ([M+
H]+). HR-EI-MS for C15H13FO2 (M+) Calcd: 244.0900; Found:
244.0895.
2-(2-Chloro-4-fluorophenyl)-1-(2-hydroxy-3-methylphenyl)-
1
ethanone (3g): H-NMR (400MHz, CDCl3) δ: 2.27 (s, 3H),
4.45 (s, 2H), 6.86 (t, J=7.6Hz, 1H), 6.97–7.02 (m, 1H),
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42.09, 114.10, 114.31, 116.82, 117.06, 118.22, 118.42, 127.34,
127.80, 128.38, 128.42, 132.46, 132.55, 135.07, 135.17, 137.41,
160.56 (C–F), 161.08, 163.04 (C–F), 202.28. Negative ESI-MS
m/z: 277.5 ([M−H]−). HR-EI-MS for C15H12ClFO2 (M+) Calcd:
278.0510; Found: 278.0505.
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1
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3H), 7.68 (t, J=4.0Hz, 1H), 12.43 (s, 1H). 13C-NMR (100MHz,
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1-(2-Hydroxy-3-methylphenyl)-2-(4-methoxyphenyl)-
1
ethanone (3i)42): H-NMR (400MHz, CDCl3) δ: 2.26 (s, 3H),
3.79 (s, 3H), 4.25 (s, 2H), 6.81 (t, J=7.8Hz, 1H), 6.89 (dd,
J=6.8, 2.0Hz, 2H), 7.19 (dd, J=6.8, 2.0Hz, 2H), 7.34 (d,
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2-(3,4-Dimethoxyphenyl)-1-(2-hydroxy-3-methylphenyl)-
1
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