Environmentally benign syntheses of flavanones

Article abstract of DOI:10.1016/j.tet.2011.04.070

Mild and environmentally benign methods for the syntheses of flavanones are described. The reaction of o-hydroxyacetophenones (1) and benzaldehydes (2) in water in the presence of DABCO at room temperature gave 3-hydroxy-1-(2- hydroxylphenyl)-3-arylpropan-1-ones (3a-i) as intermediates. Followed by an intramolecular dehydration of the 3a-i with the modified Mitsunobu's reaction, the target flavanones (4a-i) were obtained. Moreover, the reaction of 1 and 2 at the same conditions but at reflux gave flavanones in one pot with good yields.

Full text of DOI:10.1016/j.tet.2011.04.070

Tetrahedron 67 (2011) 4155e4160
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Environmentally benign syntheses of flavanones
Po-Yuan Chen a, Tzu-Pin Wang a, Michael Y. Chiang b, Keng-Shian Huang c, Cherng-Chyi Tzeng a,
,
Yi-Long Chen a, Eng-Chi Wang a
*
a Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung City 807, Taiwan
b National Sun Yat-Sen University, Kaohsiung City 804, Taiwan
c School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung 82445, Taiwan
a r t i c l e i n f o
a b s t r a c t
Article history:
Mild and environmentally benign methods for the syntheses of flavanones are described. The reaction of
o-hydroxyacetophenones (1) and benzaldehydes (2) in water in the presence of DABCO at room tem-
perature gave 3-hydroxy-1-(2-hydroxylphenyl)-3-arylpropan-1-ones (3aei) as intermediates. Followed
by an intramolecular dehydration of the 3aei with the modified Mitsunobu’s reaction, the target fla-
vanones (4aei) were obtained. Moreover, the reaction of 1 and 2 at the same conditions but at reflux
gave flavanones in one pot with good yields.
Received 17 November 2010
Received in revised form 15 April 2011
Accepted 18 April 2011
Available online 22 April 2011
Keywords:
Flavanones
Ó 2011 Elsevier Ltd. All rights reserved.
ClaiseneSchmidt reaction
Mitsunobu’s reaction
Intramolecular cyclization
1. Introduction
yield the keto-ols as the major products. Then, followed by the
cyclization of the given keto-ols using the modified Mitsunobu’s
Flavanones, which exhibited broad spectra of biological activi-
ties have attracted the interest of chemists from earlier stages to the
present. The major reported biological activities include neuron
protection,1 anti-tumor,2,3 anti-metastasis,4 antimicrobial,5 anti-
oxidant,6 anti-inflammatory,7 and antiviral activity,8 as well as
others. Flavanones, which have chemical structure embedded with
2-aryl chroman-4-one skeleton, are widely distributed in plants9
and available from synthetic sources. The major and commonly
reported synthetic methods for flavanones usually involve the
ClaiseneSchmidt reaction of o-hydroxyacetophenones with benz-
aldehydes to produce chalcone intermediates using diverse cata-
lysts,10e14 and then cyclization with various bases,15 acids,16 and
others.17 Recently, the reaction of o-hydroxyacetophenones with
benzaldehydes using LDA in THF and then cyclization with the
Mitsunobu’s reaction was reported by Lee, et al.18 Despite numer-
ous methods reported, many disadvantages on flavanone synthesis
still exist, such as by-products contamination, tedious reaction
conditions, or using toxic, corrosive, and environmentally
unfriendly reagents. Therefore to develop a new synthetic method
with environmental concerns and efficiency for flavanones is
essential and significant. Our strategy is to carry out the
ClaiseneSchmidt reaction of o-hydroxyacetophenones with benz-
aldehydes utilizing tertiary amine as base and water as solvent to
reaction,19 [DIAD (diisopropylazodicarboxylate), TPP (triphenyl-
phosphine), and Et3N] to afford the title compounds. Furthermore,
when the ClaiseneSchmidt reaction described above was carried
out at the reflux condition for 20 h, it directly provided the desired
flavanones without needs to isolate the intermediate chalcones.
Our synthetic strategy for flavanones is depicted in Scheme 1.
O
OH
Ar
R
R
i
O
O
O
ii
OH
O
R
R
3
+
Ar CHO
OH
Ar
iii
1
2
4
O
Ar
3-1
a. R = H, Ar = C6H5
b. R = H, Ar = 4-FC6H4
c. R = H, Ar = 4-ClC6H4
d. R = H, Ar = 4-BrC6H4
e. R = H, Ar = 3-BrC6H4
f. R = H, Ar = 4-NO2C6H4 i. R = Cl, Ar = 4-BrC6H4
g. R = H, Ar = 3-NO2C6H4
h. R = Cl, Ar = 4-FC6H4
Scheme 1. Benign syntheses of flavanones (a) via the ClaiseneSchmidt reaction and
the Mitsunobu’s reaction, and (b) one-pot reaction from 1 and 2. Reagents and Con-
ditions: i. DABCO, H2O, rt, 3 days, 70e92%; ii. DIAD, TPP, Et3N, THF, 0 ꢀCert, 5 hr,
75e84%; iii. DABCO, H2O, reflux, 20 hr, 67-78%
2. Results and discussion
In order to find out the best condition for giving the in-
* Corresponding author. E-mail address: enchwa@kmu.edu.tw (E.-C. Wang).
termediates 1-(2-hydroxyphenyl)-3-aryl-3-hydroxy-1-propanones
0040-4020/$ e see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2011.04.070

4156
P.-Y. Chen et al. / Tetrahedron 67 (2011) 4155e4160
(3aei), the reaction of o-hydroxyacetophenones (1a) with benzal-
dehydes (2g) utilizing various tertiary amines, such as DABCO, DBU,
or TEA as reaction base and water or ethanol as solvent were in-
vestigated. After careful examining, the reaction results were sum-
marized in Table 1.
1-(2-hydroxyphenyl)-3-(3-bromophenyl)-3-hydroxylpropanone
(3e) was carried out. Compound 3e clearly possesses the
expected skeletonwith two almost orthogonal aryl rings. The ketone
group and the phenolic hydroxyl group assume the syn configuration
obviously due to hydrogen bonding interaction. The resulting ORTEP,
coincident with structure 3e, was depicted as Fig. 1.20
Table 1
The reaction of 1a with 2g in various conditions to undergo the ClaiseneSchmidt
reaction to yield 3ga
O
O
OH
NO2
O2N
CHO
conditions
+
OH
OH
3 g
2 g
1a
Entry
Solvent
Tertiary amine
Yield (%)
1
2
3
4
5
6
7
8
H2O
EtOH
H2O
EtOH
H2O
EtOH
H2O
EtOH
H2O
EtOH
H2O
bDABCO (3 equiv)
DABCO (3 equiv)
DABCO (1 equiv)
DABCO (1 equiv)
cDBU (3 equiv)
DBU (3 equiv)
DBU (1 equiv)
DBU (1 equiv)
d TEA (3 equiv)
TEA (3 equiv)
92
71
80
60
69
59
56
42
73
70
72
69
9
10
11
12
TEA (1 equiv)
TEA (1 equiv)
EtOH
Fig. 1. ORTEP of 1-(2-hydroxyphenyl)-3-(3-bromophenyl)-3-hydroxylpropanone (3e).
a
The reaction is carried out at room temperature for 3 days.
DABCO¼1,4-diazabicyclo[2.2.2.]octane.
DBU¼1,8-diazabicyclo[5.4.0]undec-7-ene.
TEA¼triethylamine.
b
c
Subsequently, compounds 3aei were cyclized by the modified
Mitsunobu’s reaction using DIAD, TPP, and triethylamine as de-
hydration reagents to give the desired flavanones (4aei) in 75e84%
yields. All prepared flavanones have satisfactory physical and
spectral data to support the correctness of structures. Especially, in
their 1H NMR spectra, the typical signals of methylene hydrogen
atoms (H-3a and H-3b) displayed ABX type splitting pattern. This
fact offers proof for the flavanones structure. Take 4b as an example,
two nearby double doublet signals in the 1H NMR spectrum were
d
From Table 1, we found that using DABCO (3 equiv; as base) in
water at room temperature was an optimal condition for the
ClaiseneSchmidt reaction of 1a with 2g to yield 3g (entry 1). Using
1 equiv amine bases, however, lower yields were found (entries 3,
4, 7, 8, 11, and 12). Moreover, the reactive trend of solvents is
H2O>EtOH (entries 1 and 2; 5 and 6; 9 and 10), and in amine bases
is DABCO>TEA>DBU (entries 1, 9, and 5). Based on the best re-
action condition we obtained, 3-aryl-3-hydroxy-1-(2-hydroxyl-
aryl)-propan-1-ones (3aei) were given in yields of 70e92%,
respectively. Depending on their correct spectroscopic data and
elemental analysis, the structures of 3aei were verified. The
physical and spectra data of 3aei are summarized as follows
(Table 2).
observed at
d 2.88 and d 3.07 with coupling constants 16.8, 2.8 Hz
and 16.8, 13.2 Hz, respectively. This totally agrees with the expected
pattern for H-3a and H-3b. Furthermore, the double doublet signal
at
d 5.48 with coupling constants 13.2 and 2.8 Hz was again con-
sistent with the expected pattern for H-2, which coupled with H-3a
and H-3b. Moreover, in order to reduce the reaction wastes and to
increase the efficiency of the reaction, the synthesis of flavanones
(4aei) was accomplished through one-pot reaction of o-hydroxy-
acetophenones with benzaldehydes. Meanwhile, several model
reactions were designed to investigate the scope and limitation of
one-pot reaction (Table 3).
Because dehydration process occurred in the EI-MS, the
[Mþꢁ18] molecular ion peak was often found in compound 3aei. In
order to further confirm the structures of 3aei, the X-ray analysis of
Table 2
The physical and spectra data of 3aei
Compd
Yield (%)
MP (ꢀC)
H-3a dd (J)
Ha-2a dd (J)
Hb-2a dd (J)
C]O
EI-MS
M
þꢁ18
3a
3b
3c
3d
3ec
3f
3g
3hc
3ic
70
80
74
77
76
91
92
79
77
108e109 (108e110)21
119e120 (120)21
121e122 (122)21
145e146 (145)21
129e130c
5.37 (9.2, 3.0)
5.35 (8.8, 2.8)
5.35 (8.8, 3.2)
5.33 (8.8, 3.2)
5.34 (8.8, 3.2)
5.48 (m)
5.49 (m)
5.35 (9.2, 3.2)
5.33 (8.8, 3.2)
3.36 (17.6, 3.0)
3.33 (17.6, 2.8)
3.34 (17.6, 3.2)
3.34 (17.6, 3.2)
3.36 (17.6, 3.2)
3.42 (m)
3.45 (m)
3.29 (17.6, 3.2)
3.28 (17.6, 3.2)
3.46 (17.6, 9.2)
3.42 (17.6, 8.8)
3.41 (17.6, 8.8)
3.41 (17.6, 8.8)
3.42 (17.6, 8.8)
3.52 (m)
3.45 (m)
3.41 (17.6, 9.2)
3.40 (17.6, 9.2)
C]Ob
205.4
205.3
205.2
205.1
205.1
204.6
204.7
204.4
224
242
258
301
301
269
269
276
335
153e154 (156)22
130e131 (127e129)22
149e150c
150e151c
a
Measured in 1H NMR (CDCl3, 400 MHZ).
Measured in 13C NMR (CDCl3, 100 MHZ).
New compound.
b
c

P.-Y. Chen et al. / Tetrahedron 67 (2011) 4155e4160
4157
Table 3
Investigation the scope and limitation of the one-pot reaction using various tertiary aminesa
O
O
O
OH
O
CHO
3o amines
+
R
R
+
OH
OH
R
1a
2
3
4
Entry
3ꢀ Amine (3 equiv)
Yield (%)b 3
Yield (%) 4
1 (R¼H)
DABCO
DBU
TEA
DMAP
DABCO
DBU
19
38
24
15
17
46
32
29
20
53
21
15
19
20
0
67
21
59
38
69
28
64
43
76
32
73
66
70
78
0
2
3
4c
5 (R¼ 3-Br)
6
7
8
TEA
DMAP
DABCO
DBU
9 (R¼ 3-NO2)
10
11
12
TEA
DABCO
DABCO
DABCO
DABCO
13 (R¼4-Br)
14 (R¼4-NO2)
15d (R¼4-OMe)
a
The reaction was carried out at reflux in water for 20 h.
Compounds were isolated and purified by column chromatography.
DMAP¼N,N-dimethylaminopyridine.
b
c
d
Recovery starting material.
As shown in Table 3, the reaction using DABCO (3 equiv) as
13e15) to figure out the scope and limitation. We found that
benzaldehydes bearing an electron-withdrawing group worked
well under the presence of DABCO (3 equiv) at reflux in water for
20 h, the reactions proceeded successfully to afford the flavanones
4 in good yields (entries 5, 9, and 13e14). Obviously, benzaldehyde
with the electron-donating group to react with compound 1a
(entry 15), no desired product was detected but with the recovery
of starting material. Apparently, for benzaldehydes (2) with an
electron-withdrawing group facilitates the one-pot reaction, and
with an electron-donating group decreases the reaction. There-
fore, depending on the results of our investigation, the effect of
substituents of benzaldehydes in this one-pot reaction can be
deduced as the following trend: 4-NO2>3-NO2>4-Br>3-
Br>H>>4-OCH3. All flavanones obtained from one-pot reaction
and from two-steps are identical by comparing their physical and
spectral data. The physical and spectra data of 4aei were sum-
marized in Table 4.
base, water as solvent and reflux promoted the reaction of 1 with
2 in one pot to give 4 in yields of 67e76% (entries 1, 5, and 9). On
the other hand DBU a sterically hindered base23 used as a re-
action base rendered reduced yields of 4 (21e32%) (entries 2, 6,
and 10). As reaction base TEA, which is less soluble in water
afforded the expected 4 in 59e73% yields (entries 3, 7, and 11).
Parallelly, using DMAP a weak base as reaction base compound 4
was afforded in slightly lower yields (38e66%) (entries 4, 8, and
12). Resulting from our experimental results, BABCO was found to
be a better base than other tertiary bases in running one-pot
reaction of 1 and 2 to yield 4. Thus, the trend of reaction base is
DABCO>TEA>DMAP>DBU.
Besides the reaction bases, the structure of benzaldehydes,
which may influence the reaction of 1 with 2 to yield 4 was in-
vestigated. Therefore various benzaldehydes (2) were explored to
react with o-hydroxyacetophenone (1a) (entries 1, 5, 9, and
Table 4
The physical and the selected spectral data of 4aei
O
a. R = H, Ar = C6H5
b. R = H, Ar = 4-FC6H4
c. R = H, Ar = 4-ClC6H4
d. R = H, Ar = 4-BrC6H4
e. R = H, Ar = 3-BrC6H4
f. R = H, Ar = 4-NO2C6H4
R
4
3
2
g. R = H, Ar = 3-NO2C6H4
h. R = Cl, Ar = 4-FC6H4
i. R = Cl, Ar = 4-BrC6H4
1
O
Ar
4
Compd
Yield (%)
MP (ꢀC)
H-2 dd (J)
Ha-3 dd (J)
Hb-3 dd (J)
C]O
EI-MS
Mþ
4a
4b
4c
4d
4ec
4f
4g
4hc
4ic
75a (67)b
75 (71)
78 (70)
79 (70)
77 (69)
79 (78)
84 (76)
82 (74)
80 (72)
70e71 (73e75)24
79e80 (78e79)24
85e86 (84e85)18
5.49 (13.2, 2.8)
5.48 (13.2, 2.8)
5.47 (13.2, 3.2)
5.46 (13.2, 2.8)
5.45 (13.2, 2.8)
5.62 (12.4, 3.6)
5.61 (12.8, 3.2)
5.46 (13.2, 2.8)
5.44 (12.8, 3.2)
2.90 (16.8, 2.8)
2.88 (16.8, 2.8)
2.88 (17.2, 3.2)
2.88 (16.8, 3.2)
2.89 (16.8, 3.2)
2.96 (16.8, 3.6)
2.96 (16.8, 3.2)
2.89 (16.8, 2.8)
2.89 (16.8, 3.2)
3.10 (16.8, 13.2)
3.07 (16.8, 13.2)
3.05 (17.2, 13.2)
3.04 (16.8, 13.2)
3.04 (16.8, 13.6)
3.04 (16.8, 12.4)
3.08 (16.8, 12.8)
3.06 (16.8, 13.2)
3.02 (16.8, 12.8)
192.0
191.8
191.5
191.5
191.4
190.7
190.8
190.6
190.4
224
242
258
301
301
269
269
276
335
116e117(115.8e119)3
102e103
120e121(118e119)25
145e146 (142)22
149e150
151e152
a
Isolated yields from column chromatography after the reaction of 3 with the Mitzunobu’s reaction.
Isolated yields obtained from the reaction of 1 and 2 in one pot.
New compounds.
b
c

4158
P.-Y. Chen et al. / Tetrahedron 67 (2011) 4155e4160
3. Conclusion
8.8 Hz, 1H, ArCOCHaHbCHOH), 5.35 (dd, J¼8.8, 3.2 Hz, 1H, ArCO-
CHaHbCHOH), 6.89 (td, J¼8.4, 1.2 Hz, 1H, ArH), 7.01 (dd, J¼8.4,
0.8 Hz, 1H, ArH), 7.08 (m, 2H, Ar0H), 7.42 (m, 2H, ArH), 7.50 (td,
J¼8.4, 1.2 Hz, 1H, ArH), 7.70 (dd, J¼8.0, 1.2 Hz, 1H, ArH), 12.0 (s, 1H,
We have successfully developed environmentally benign syn-
theses for flavanones. In our synthetic procedures, no corrosive
acids or bases and no catalyst were used. Most importantly, we
have demonstrated that the use of water as the solvent and DABCO
as the base for the ClaiseneSchmidt reaction at room temperature
to prepare intermediate 3-aryl-3-hydroxy-1-(2-hydroxylaryl)
propan-1-ones as well as the cyclization to yield flavanones using
the modified Mitsunobu’s reagent. Moreover, at the same condi-
tions but at reflux avoided to isolate keto-ols (3) and chalcones
provides a mild, concise, efficient, and one pot method for
flavanones.
ArOH); 13C NMR (CDCl3, 100 MHz)
d
47.1, 69.3, 115.5 (d, J¼21.2 Hz),
118.7, 119.2, 119.3, 127.4 (d, J¼7.6 Hz), 130.0, 137.0, 138.4 (d,
J¼3.0 Hz), 162.3 (d, J¼224.0 Hz), 162.6, 205.3; EI-MS (70 eV) m/z (rel
intensity, %) 242 (Mþ, ꢁ18, 56), 241 (100), 225 (21), 147 (29), 123
(16), 121 (33), 120 (16), 92 (15). Anal. Calcd for C15H13FO3: C, 69.22;
H, 5.03. Found: C, 68.82; H, 5.01.
4.1.1.3. 3-(4-Chlorophenyl)-3-hydroxy-1-(2-hydroxyphenyl)-
propan-1-one (3c). Compound 3c (1.50 g, 74%) was obtained as
colorless crystals, mp¼121e122 ꢀC (lit.21 mp 122 ꢀC); Rf¼0.54 (ethyl
acetate/n-hexane¼1:3); IR (KBr) cmꢁ1: 1635 (C]O) and 3525 (OH);
4. Experimental
4.1. General
1H NMR (CDCl3, 400 MHz)
d
3.34 (dd, J¼17.6, 3.2 Hz, 1H, ArCO-
CHaHbCHOH), 3.39 (s, 1H, ArCOCHaHbeCHOH), 3.41 (dd, J¼17.6,
8.8 Hz, 1H, ArCOCHaHbCHOH), 5.35 (dd, J¼8.8, 3.2 Hz, 1H, ArCO-
CHaHbCHOH), 6.89 (td, J¼8.0,1.2 Hz,1H, ArH), 7.01 (dd, J¼8.4,1.2 Hz,
1H, ArH), 7.37 (m, 4H, ArH), 7.50 (td, J¼8.4,1.6 Hz,1H, ArH), 7.68 (dd,
J¼8.4, 2.0 Hz, 1H, ArH), 12.0 (s, 1H, ArOH); 13C NMR (CDCl3,
Melting points (Yanaco micro melting-point apparatus) were
uncorrected. 1H NMR and 13C NMR spectra were obtained on
a Varian Unity plus 400 Spectrometer. Chemical shifts were mea-
sured in parts per million with respect to TMS. IR spectra were run
on a PerkineElmer spectrometer. Elemental analyses were recor-
ded on a Heraeus CHN-O Rapid analyzer. Mass spectra were
recorded on a Chem/hp/middle spectrometer connected to a Hew-
lett Packard series II model gas-liquid chromatography. HRMS
spectra were performed on a JEOL JMS SX/SX 102A instrument.
Silica gel (230e400 mesh) for column chromatography and pre-
coated silica-gel plates (60 F-254) for TLC were purchased from E.
Merck Co. UV light (254 nm) was used to detect spots on TLC plates
after development.
100 MHz)
d 47.0, 69.2, 118.7, 119.2, 119.3, 127.1, 128.8, 129.9, 133.5,
137.0, 141.1, 162.6, 205.2; EIMS (70 eV) m/z (rel intensity, %) 258
(Mþ, ꢁ18, 60), 257 (100), 147 (72), 121 (35), 120 (29), 102 (35), 92
(37), 75 (26). Anal. Calcd for C15H13ClO3: C, 65.11; H, 4.74. Found: C,
65.14; H, 4.70.
4.1.1.4. 3-(4-Bromophenyl)-3-hydroxy-1-(2-hydroxyphenyl) pro-
pan-1-one (3d). Compound 3d (1.82g, 77%) was obtained as color-
less crystals, mp¼145e146 ꢀC (lit.21 mp 145 ꢀC); Rf¼0.67 (ethyl ac-
etate/n-hexane¼1:3); IR (KBr) cmꢁ1: 1630 (C]O) and 3519 (OH); 1H
NMR (CDCl3, 400 MHz)
d
3.34 (dd, J¼17.6, 3.2 Hz, 1H, ArCOCHaHb
-
4.1.1. General procedure for the preparation of 3-aryl-3-hydroxy-1-
(2-hydroxylaryl)propan-1-ones (3aei). The mixture of 2-hydroxy-
acetophenones (1a,b) (7.3 mmol) and benzaldehydes (2aei)
(7.3 mmol) in H2O (30 mL) was stirred, and then added DABCO
(2.45 g, 21.9 mmol). The resulting mixture was continually stirred at
room temperature for 3 days. Then, the reaction mixture was
extracted with dichloromethane (3ꢂ50 mL). The resulting extracts
were combined, washed with brine, and dried over anhydrous
MgSO4 in sequence. After filtration, the filtrate was concentrated in
vacuo to give crude 3aei. The given crude products were further
purify from silica-gel column chromatography (ethyl acetate/n-
hexane¼1:5) to yield pure 3aei.
CHOH), 3.39 (s, 1H, ArCOCHaHbeCHOH), 3.41 (dd, J¼17.6, 8.8 Hz, 1H,
ArCOCHaHbCHOH), 5.33 (dd, J¼8.8, 3.2 Hz, 1H, ArCOCHaHbCHOH),
6.89 (td, J¼8.0, 1.2 Hz, 1H, ArH), 7.01 (dd, J¼8.8, 1.2 Hz, 1H, ArH), 7.32
(m, 1H, Ar0H), 7.50 (td, J¼8.4, 1.6 Hz, 1H, ArH), 7.68 (dd, J¼8.0, 1.6 Hz,
1H, ArH), 12.0 (s, 1H, ArOH); 13C NMR (CDCl3, 100 MHz)
d 47.0, 69.2,
118.7, 119.2, 119.3, 121.6, 127.5, 130.0, 131.7, 137.1, 141.7, 162.6, 205.1;
EIMS (70 eV) m/z (rel intensity, %) 303 (Mþ, ꢁ18, 100), 302 (66), 301
(85), 223 (60), 207 (43), 148 (43), 147 (79), 121 (46), 103 (60). Anal.
Calcd for C15H13BrO3: C, 56.10; H, 4.08. Found: C, 56.05; H, 4.10.
4.1.1.5. 3-(3-Bromophenyl)-3-hydroxy-1-(2-hydroxyphenyl)
propan-1-one (3e). Compound 3e (1.56 g, 76%) was obtained as
colorless crystals, mp¼129e130 ꢀC; Rf¼0.44 (ethyl acetate/n-
hexane¼1:3); IR (KBr) cmꢁ1: 1641 (C]O) and 3464 (OH); 1H NMR
4.1.1.1. 3-Hydroxy-1-(2-hydroxyphenyl)-3-phenylpropan-1-one
(3a). Compound 3a (1.69 g, 70%) was obtained as colorless crystals,
mp¼108e109 ꢀC (lit.21 mp 108e110 ꢀC); Rf¼0.58 (ethyl acetate/n-
hexane¼1:3); IR (KBr) cmꢁ1: 1634 (C]O) and 3466 (OH); 1H NMR
(CDCl3, 400 MHz)
d
3.33 (s, 1H, ArCOCHaHbCHOH), 3.36 (dd, J¼17.6,
3.2 Hz, 1H, ArCOCHaHbCHOH), 3.42 (dd, J¼17.6, 8.8 Hz, 1H, ArCO-
CHaHbCHOH), 5.34 (dd, J¼8.8, 3.2 Hz, 1H, ArCOCHaHbCHOH), 6.90
(td, J¼8.4, 1.2 Hz, 1H, ArH), 7.00 (m, 1H, ArH), 7.47 (m, 5H, ArH), 7.69
(dd, J¼8.0, 1.6 Hz, 1H, ArH), 12.0 (s, 1H, ArOH); 13C NMR (CDCl3,
(CDCl3, 400 MHz)
d 3.25 (s, 1H, ArCOeCHaHbCHOH), 3.36 (dd,
J¼17.6, 3.0 Hz, 1H, ArCOCHaHbeCHOH), 3.46 (dd, J¼17.6, 9.2 Hz, 1H,
ArCOCHaHbCHOH), 5.37 (dd, J¼9.2, 3.0 Hz, 1H, ArCOCHaHbCHOH),
6.89 (td, J¼8.0, 0.8 Hz, 1H, ArH), 7.00 (dt, J¼8.4, 0.8 Hz, 1H, ArH),
7.32 (td, J¼8.8, 1.6 Hz, 1H, ArH), 7.44 (m, 5H, ArH), 7.70 (dd, J¼8.0,
100 MHz)
d 47.0, 69.1, 118.7, 119.2, 122.8, 124.4, 128.9, 130.0, 130.2,
130.9, 137.1, 143.6, 144.9, 162.6, 205.1; EIMS (70 eV) m/z (rel in-
tensity, %) 303 (Mþ, ꢁ18, 39), 302 (34), 301 (34), 224 (20), 147 (100),
120 (41), 103 (20), 92 (38). Anal. Calcd for C15H13BrO3: C, 56.10; H,
4.08. Found: C, 56.12; H, 4.11.
1.6 Hz,1H, ArH),12.1 (s,1H, ArOH); 13C NMR (CDCl3,100 MHz)
d 47.1,
69.8, 118.7, 119.1, 119.4, 125.7, 127.9, 128.7, 130.0, 136.9, 142.7, 162.6,
205.4; EIMS (70 eV) m/z (rel intensity, %) 224 (Mþ, ꢁ18, 57), 223
(100), 147 (35), 120 (23), 105 (20), 93 (20), 92 (27), 78 (14). Anal.
Calcd for C15H14O3: C, 74.36; H, 5.82. Found: C, 73.86; H, 5.85.
4.1.1.6. 3-Hydroxy-1-(2-hydroxyphenyl)-3-(4-nitrophenyl)-
propan-1-one (3f). Compound 3f (1.79 g, 91%) was obtained as
colorless crystals, mp¼153e154 ꢀC (lit.22 mp 156 ꢀC); Rf¼0.44 (ethyl
acetate/n-hexane¼1:3); IR (KBr) cmꢁ1: 1640 (C]O) and 3529 (OH);
4.1.1.2. 3-(4-Fluorophenyl)-3-hydroxy-1-(2-hydroxyphenyl)
-propan-1-one (3b). Compound 3b (2.08 g, 80%) was obtained as
colorless crystals, mp¼119e120 ꢀC (lit.21 mp 120 ꢀC); Rf¼0.74 (ethyl
acetate/n-hexane¼1:3); IR (KBr) cmꢁ1: 1637 (C]O) and 3269 (OH);
1H NMR (CDCl3, 400 MHz)
d 3.41 (s, 1H, ArCOCHaHbCHeOH), 3.42
(m, 1H, ArCOCHaHbCHOH), 3.52 (m, 1H, ArCOeCHaHbCHOH), 5.48
(m, 1H, ArCOCHaHbCHOH), 6.90 (td, J¼8.4, 1.2 Hz, 1H, ArH), 7.02 (dd,
J¼8.4, 1.2 Hz, 1H, ArH), 7.51 (m, 1H, ArH), 7.65 (td, J¼8.8, 1.6 Hz, 3H,
ArH), 8.25 (dd, J¼8.8, 1.6 Hz, 2H, ArH), 12.0 (s, 1H, ArOH); 13C NMR
1H NMR (CDCl3, 400 MHz)
d
3.33 (dd, J¼17.6, 3.2 Hz, 1H, ArCO-
CHaHbCHOH), 3.39 (s, 1H, ArCOCHaHbCHOH), 3.42 (dd, J¼17.6,

P.-Y. Chen et al. / Tetrahedron 67 (2011) 4155e4160
4159
(CDCl3, 100 MHz)
d
46.79, 68.93, 118.8, 119.1, 119.3, 123.9, 126.6,
1H NMR (CDCl3, 400 MHz)
d
2.90 (dd, J¼16.8, 2.8 Hz, 1H, Ha-3), 3.10
129.9, 137.3, 147.9, 149.8, 162.6, 204.6; EIMS (70 eV) m/z (rel in-
tensity, %) 269 (Mþ, ꢁ18, 43), 268 (66), 252 (24), 207 (40), 148 (27),
147 (74), 120 (53), 93 (100). Anal. Calcd for C15H13NO5: C, 62.72; H,
4.56; N, 4.88. Found: C, 62.66; H, 4.61; N, 4.84.
(dd, J¼16.8, 13.2 Hz, 1H, Hb-3), 5.49 (dd, J¼13.2, 2.8 Hz, 1H, H-2),
7.06 (m, 2H, ArH), 7.47 (m, 5H, ArH), 7.94 (dd, J¼8.4, 2.0 Hz, 1H,
ArH); 13C NMR (CDCl3, 100 MHz)
d 44.7, 79.6, 118.1, 120.9, 121.6,
126.1, 127.0, 128.8, 128.9, 136.2, 138.7, 161.5, 192.0; EIMS (70 eV) m/z
(rel intensity, %) 224 (Mþ, 56), 223 (100),147 (62),120 (47),104 (26),
92 (78), 78(29), 63 (22). Anal. Calcd for C15H12O2: C, 80.34; H, 5.39.
Found: C, 80.02; H, 5.47.
4.1.1.7. 3-Hydroxy-1-(2-hydroxyphenyl)-3-(3-nitrophenyl)
-propan-1-one (3g). Compound 3g (1.82 g, 92%) was obtained as
colorless crystals, mp¼130e131 ꢀC (lit.22 mp 127e129 ꢀC); Rf¼0.44
(ethyl acetate/n-hexane¼1:3); IR (KBr) cmꢁ1: 1638 (C]O) and
4.1.2.2. 40-Fluoroflavanone (4b). Compound 4b (0.31 g, 75%) was
obtained as colorless crystals, mp¼79e80 ꢀC (lit.24 mp 78e79 ꢀC);
Rf¼0.48 (ethyl acetate/n-hexane¼1:4); IR (KBr) cmꢁ1: 1695 (C]O);
3529 (OH); 1H NMR (CDCl3, 400 MHz)
d 3.45 (m, 1H, ArCOCHaHb
-
CHOH), 3.45 (m, 1H, ArCOCHaHbCHOH), 5.49 (m, 1H, ArCOCH2
-
1H NMR (CDCl3, 400 MHz)
d
2.88 (dd, J¼16.8, 2.8 Hz, 1H, Ha-3), 3.07
CHOH), 6.91 (td, J¼8.4, 1.2 Hz, 1H, ArH), 7.02 (dd, J¼8.4, 1.2 Hz, 1H,
ArH), 7.52 (td, J¼8.4,1.6 Hz,1H, ArH), 7.57 (t, J¼8.0 Hz,1H, ArH), 7.69
(dd, J¼8.4, 2.0 Hz,1H, ArH), 7.80 (m,1H, ArH), 8.18 (m,1H, ArH), 8.34
(t, J¼1.6 Hz, 1H, ArH), 12.0 (s, 1H, ArOH); 13C NMR (CDCl3, 100 MHz)
(dd, J¼16.8, 13.2 Hz, 1H, Hb-3), 5.48 (dd, J¼13.2, 2.8 Hz, 1H, H-2),
7.10 (m, 4H, ArH), 7.47 (m, 2H, ArH), 7.52 (td, J¼8.4, 1.6 Hz, 1H, ArH),
7.93 (dd, J¼8.0, 2.0 Hz, 1H, ArH); 13C NMR (CDCl3, 100 MHz)
d 44.7,
d
46.8, 68.8, 118.8, 119.1, 119.3, 120.9, 122.8, 129.6, 129.9, 131.9, 137.3,
78.9, 115.8 (d, J¼21.3 Hz), 118.1, 120.9, 121.8, 127.1, 128.0 (d,
J¼8.3 Hz), 134.6, 136.3, 161.4, 162.8 (d, J¼246.3 Hz), 191.8; EIMS
(70 eV) m/z (rel intensity, %) 242 (Mþ, 56), 241 (87), 147 (43), 122
(41), 121 (36), 120 (67), 92 (100), 63 (23). Anal. Calcd for C15H11FO2:
C, 74.37; H, 4.58. Found: C, 74.31; H, 4.58.
144.7, 148.4, 162.6, 204.7; EIMS (70 eV) m/z (rel intensity, %) 269
(Mþ, ꢁ18, 74), 268 (89), 148 (69), 147 (100), 122 (67), 120 (82), 93
(34), 92 (93). Anal. Calcd for C15H13NO5: C, 62.72; H, 4.56; N, 4.88.
Found: C, 62.67; H, 4.59; N, 4.82.
4.1.1.8. 1-(5-Chloro-2-hydroxyphenyl)-3-(4-fluorophenyl)-3-hy-
droxypropan-1-one (3h). Compound 3h (1.70 g, 79%) was obtained
as colorless crystals, mp¼93e94 ꢀC; Rf¼0.67 (ethyl acetate/n-
hexane¼1:3); IR (KBr) cmꢁ1: 1640 (C]O) and 3432 (OH); 1H NMR
4.1.2.3. 40-Chloroflavanone (4c). Compound 4c (0.32 g, 78%) was
obtained as colorless crystals, mp¼85e86 ꢀC (lit.18 mp 84e85 ꢀC);
Rf¼0.48 (ethyl acetate/n-hexane¼1:4); IR (KBr) cmꢁ1: 1692 (C]O);
1H NMR (CDCl3, 400 MHz)
d
2.88 (dd, J¼17.2, 3.2 Hz, 1H, Ha-3), 3.05
(CDCl3, 400 MHz)
d
3.12 (s, 1H, ArCOCHaHbCHOH), 3.29 (dd, J¼17.6,
(dd, J¼17.2, 13.2 Hz, 1H, Hb-3), 5.47 (dd, J¼13.2, 3.2 Hz, 1H, H-2),
3.2 Hz, 1H, ArCOCHaHbCHOH), 3.41 (dd, J¼17.6, 9.2 Hz, 1H, ArCO-
CHaHbCHOH), 5.35 (dd, J¼9.2, 3.2 Hz, 1H, ArCOCHaHbCHOH), 6.97
(d, J¼8.8 Hz, 1H, ArH), 7.08 (td, J¼9.2, 2.8 Hz, 2H, ArH), 7.42 (m, 3H,
ArH), 7.65 (d, J¼2.4 Hz, 1H, ArH), 11.9 (s, 1H, ArOH); 13C NMR (CDCl3,
7.07 (m, 2H, ArH), 7.42 (m, 4H, ArH), 7.52 (td, J¼8.4, 1.6 Hz, 1H, ArH),
7.93 (dd, J¼8.0, 2.0 Hz, 1H, ArH); 13C NMR (CDCl3, 100 MHz)
d 44.6,
78.8, 118.1, 120.9, 121.8, 127.1, 127.5, 129.0, 134.6, 136.3, 137.2, 161.3,
191.5; 13C NMR (CDCl3, 100 MHz)
d 44.58, 78.80, 118.1, 120.9, 121.8,
100 MHz)
d
47.3, 69.1, 115.6 (d, J¼21.2 Hz), 119.8, 120.4, 123.9, 127.4
127.1, 127.5, 129.0, 134.6, 136.3, 137.2, 161.3, 191.5; EIMS (70 eV) m/z
(rel intensity, %) 258 (Mþ, 71), 257 (100), 223 (29), 147 (66), 138
(37), 120 (67), 103 (37), 92 (75). Anal. Calcd for C15H11ClO2: C, 69.64;
H, 4.29. Found: C, 69.53; H, 4.30.
(d, J¼8.4 Hz), 129.2, 136.9, 138.2, 161.0 (d, J¼256.9 Hz), 163.6, 204.4;
EIMS (70 eV) m/z (rel intensity, %) 276 (Mþ, ꢁ18, 99), 275 (100), 183
(33), 181 (53), 156 (31), 155 (31), 154 (78), 122 (29). Anal. Calcd for
C15H12ClFO3: C, 61.13; H, 4.10. Found: C, 61.10; H, 4.11.
4.1.2.4. 40-Bromoflavanone (4d). Compound 4d (0.38 g, 79%)
was obtained as colorless crystals, mp¼116e117 ꢀC (lit.3 mp
115.8e119 ꢀC); Rf¼0.49 (ethyl acetate/n-hexane¼1:4); IR (KBr)
4.1.1.9. 3-(4-Bromophenyl)-1-(5-chloro-2-hydroxyphenyl)-3-hy-
droxypropan-1-one (3i). Compound 3i (1.98 g, 77%) was obtained as
colorless crystals, mp¼103e104 ꢀC; Rf¼0.61 (ethyl acetate/n-
hexane¼1:3); IR (KBr) cmꢁ1: 1638 (C]O) and 3447 (OH); 1H NMR
cmꢁ1: 1687 (C]O); 1H NMR (CDCl3, 400 MHz)
d
2.88 (dd, J¼16.8,
3.2 Hz, 1H, Ha-3), 3.04 (dd, J¼16.8, 13.2 Hz, 1H, Hb-3), 5.46 (dd,
J¼13.2, 2.8 Hz, 1H, H-2), 7.07 (m, 2H, ArH), 7.37 (dd, J¼8.4, 1.6 Hz,
2H, ArH), 7.56 (td, J¼8.4, 1.6 Hz, 1H, ArH), 7.57 (dd, J¼8.4, 2.0 Hz, 2H,
ArH), 7.93 (dd, J¼8.0, 2.0 Hz, 1H, ArH); 13C NMR (CDCl3, 100 MHz)
(CDCl3, 400 MHz)
d
3.15 (s, 1H, ArCOCHaHbCHOH), 3.28 (dd, J¼17.6,
3.2 Hz, 1H, ArCOCHaHbCHOHAr0), 3.40 (dd, J¼17.6, 9.2 Hz, 1H,
ArCOCHaHbCHOH), 5.33 (dd, J¼8.8, 3.2 Hz, 1H, ArCOCHaHbCHOH),
6.97 (d, J¼8.8 Hz, 1H, AreH), 7.31 (td, J¼8.8, 2.4 Hz, 2H, AreH), 7.44
(dd, J¼8.8, 2.4 Hz, 1H, ArH), 7.52 (td, J¼9.2, 2.4 Hz, 2H, ArH), 7.63 (d,
J¼2.4 Hz, 1H, ArH), 11.9 (s, 1H, ArOH); 13C NMR (CDCl3, 100 MHz)
d
44.5, 78.8, 118.1, 120.9, 121.8, 122.7, 127.1, 127.8, 132.0, 136.3, 137.8,
161.3, 191.5; EIMS (70 eV) m/z (rel intensity, %) 303 (Mþ, 45), 302
(26), 301 (39), 223 (49), 147 (88), 120 (62), 103 (72), 93(100). Anal.
Calcd for C15H11BrO2: C, 59.43; H, 3.66. Found: C, 59.36; H, 3.71.
d
47.1, 69.1, 119.8, 120.4, 121.8, 123.9, 127.4, 129.1, 131.8, 136.9, 141.4,
161.0, 204.2; EIMS (70 eV) m/z (rel intensity, %) 337 (Mþ, ꢁ18, 66),
336 (44), 335 (46), 183 (46), 182 (66), 181 (100), 154 (79), 102 (51).
Anal. Calcd for C15H12BrClO3: C, 50.66; H, 3.40. Found: C, 50.49;
H, 3.38.
4.1.2.5. 30-Bromoflavanone (4e). Compound 4e (0.37 g, 77%) was
obtained as colorless crystals, mp¼102e103 ꢀC; Rf¼0.50 (ethyl ac-
etate/n-hexane¼1:4); IR (KBr) cmꢁ1: 1692 (C]O); 1H NMR (CDCl3,
400 MHz)
d
2.89 (dd, J¼16.8, 3.2 Hz, 1H, Ha-3), 3.04 (dd, J¼16.8,
4.1.2. General procedure for the preparation of flavavones
(4aei). Under argon, the solution of 3aei (1.6 mmol), TPP (0.46 g,
1.6 mmol), and Et3N (0.18 g, 1.6 mmol) in THF (20 mL) at 0 ꢀC was
stirred and added DIAD (0.43 g, 1.9 mmol) in drops. The resulting
mixture was continually stirred from 0 ꢀC to room temperature for
5 h. After concentration in vacuo, the obtained residue was further
purified from silica-gel column chromatography (ethyl acetate/n-
hexane¼1:10) to give pure 4aei.
13.6 Hz, 1H, Hb-3), 5.45 (dd, J¼13.2, 2.8 Hz, 1H, H-2), 7.08 (m, 2H,
ArH), 7.31 (t, J¼8.0 Hz, 1H, ArH), 7.53 (m, 2H, ArH), 7.68 (t, J¼1.6 Hz,
1H, ArH), 7.93 (dd, J¼8.4, 2.0 Hz, 1H, ArH); 13C NMR (CDCl3,
100 MHz)
d 44.6, 78.7, 118.1, 120.8, 121.9, 122.9, 124.6, 127.1, 129.2,
130.4, 131.8, 136.3, 141.1, 161.2, 191.4; EIMS (70 eV) m/z (rel intensity,
%) 303 (Mþ, 43), 302 (36), 301 (33), 148 (28), 147 (100), 121 (24),120
(45), 92 (49). Anal. Calcd for C15H11BrO2: C, 59.43; H, 3.66. Found: C,
59.40; H, 3.65.
4.1.2.6. 40-Nitroflavanone (4f). Compound 4f (0.34 g, 79%) was
obtained as colorless crystals, mp¼120e121 ꢀC (lit.25 mp
4.1.2.1. Flavanone (4a). Compound 4a (0.27 g, 75%) was
obtained as colorless crystals, mp¼70e71 ꢀC (lit.24 mp 73e75 ꢀC);
Rf¼0.53 (ethyl acetate/n-hexane¼1:4); IR (KBr) cmꢁ1:1688 (C]O);
118e119 ꢀC); Rf¼0.35 (ethyl acetate/n-hexane¼1:4); IR (KBr) cmꢁ1
:

4160
P.-Y. Chen et al. / Tetrahedron 67 (2011) 4155e4160
1691 (C]O); 1H NMR (CDCl3, 400 MHz)
d
2.96 (dd, J¼16.8, 3.6 Hz,
(70%), 4e (69%), 4f (78%), 4g (76%), 4h (74%), and 4i (72%) were
obtained, respectively.
1H, Ha-3), 3.04 (dd, J¼16.8, 12.4Hz, 1H, Hb-3), 5.62 (dd, J¼12.4,
3.6 Hz, 1H, H-2), 7.11(m, 2H, ArH), 7.56 (td, J¼8.4, 1.6 Hz, 1H, ArH),
7.69 (dd, J¼8.4, 2.0 Hz, 2H, ArH), 7.95 (dd, J¼8.0, 2.0 Hz, 1H, ArH),
Acknowledgements
8.31 (dd, J¼8.8, 2.0 Hz, 2H, ArH); 13C NMR (CDCl3, 100 MHz)
d 44.6,
78.3, 118.0, 120.9, 122.2, 124.1, 126.8, 127.2, 136.5, 136.3, 148.8, 160.9,
190.7; EIMS (70 eV) m/z (rel intensity, %) 269 (Mþ, 33), 268 (49), 252
(18), 147 (91), 121 (20), 120 (53), 93 (100), 64 (13). Anal. Calcd for
C15H11NO4: C, 66.91; H, 4.12; N, 5.20. Found: C, 66.82; H, 4.13; N,
5.10.
The research grants from the National Science Council (NSC-99-
2113-M-037-007) and Kaohsiung Medical University (N-843) of
Taiwan are grateful.
References and notes
4.1.2.7. 30-Nitroflavanone (4g). Compound 4g (0.36 g, 84%) was
obtained as colorless crystals, mp¼145e146 ꢀC (lit.22 mp 142 ꢀC);
Rf¼0.31(ethyl acetate/n-hexane¼1:4); IR (KBr) cmꢁ1:1693 (C]O);
1. Vauzour, D.; Vafeiadou, K.; Rice-Evans, C.; Williams, R. J.; Spencer, J. P. E. J.
Neurochem. 2007, 103, 1355e1367.
2. Agarwal, C.; Tyagi, A.; Kaur, M.; Agarwal, R. Carcinogenesis 2007, 28, 1463e1470.
3. Cabrera, M.; Simoens, M.; Falchi, G.; Lavaggi, M. L.; Piro, O. E.; Castellano, E. E.;
Vidal, A.; Azqueta, A.; Monge, A.; Lopez de Cerain, A.; Sagrera, G.; Seoane, G.;
Cerecetto, H.; Gonzalez, M. Bioorg. Med. Chem. 2007, 15, 3356e3367.
4. Hsiao, Y. C.; Kuo, W. H.; Chen, P. N.; Chang, H. R.; Lin, T. H.; Yang, W. E.; Hsieh, Y.
S.; Chu, S. C. Chem.-Biol. Interact. 2007, 167, 193e206.
1H NMR (CDCl3, 400 MHz)
d
2.96 (dd, J¼16.8, 3.2 Hz, 1H, Ha-3), 3.08
(dd, J¼16.8, 12.8 Hz, 1H, Hb-3), 5.61 (dd, J¼12.8, 3.2 Hz, 1H, H-2),
7.11 (m, 2H, ArH), 7.56 (td, J¼8.4, 1.6 Hz, 1H, ArH), 7.64 (t, J¼8.0 Hz,
1H, ArH), 7.81 (m,1H, ArH), 7.95 (dd, J¼8.0,1.6 Hz,1H, ArH), 8.26 (m,
1H, ArH), 8.42 (t, J¼2.0 Hz, 1H, ArH); 13C NMR (CDCl3, 100 MHz)
5. Ward, F. E.; Garling, D. L.; Buckler, R. T.; Lawler, D. M.; Cummings, D. P. J. Med.
Chem. 1981, 24, 1073e1077.
6. (a) Choi, Y. J.; Lee, M. K.; Lee, Y. J.; Jeong, Y. J.; Yoon Park, J. H.; Sung, L. S.; Kang,
Y. H. J. Med. Food 2004, 7, 408e416; (b) Varga, Z.; Seres, I.; Nagy, E.; Ujhelyi, L.;
Balla, G.; Balla, J.; Antus, S. Phytomedicine 2006, 13, 85e93; (c) Sun, J. M.; Yang,
J. S.; Zhang, H. Chem. Pharm. Bull. 2007, 55, 474e476; (d) Jung, H. A.; Jeong, D.
M.; Chung, H. Y.; Lim, H. A.; Kim, J. Y.; Yoon, N. Y.; Choi, J. S. Biol. Pharm. Bull.
2008, 31, 908e915.
7. (a) Njamen, D.; Mbafor, J. T.; Fomum, Z. T.; Kamanyi, A.; Mbanya, J. C.; Recio, M.
C.; Giner, R. M.; Manez, S.; Rios, J. L. Planta Med. 2004, 70, 104e107; (b) Ueda, H.;
Yamazaki, C.; Yamazaki, M. Biosci. Biotechnol. Biochem. 2004, 68, 119e125; (c)
Rotelli, A. E.; Guardia, Teresita; Juarez, Americo Osvaldo; De la Rocha, Nadir
Ernesto; Pelzer, L. E. Pharm. Res. 2003, 48, 601e606.
8. (a) Paredes, A.;Alzuru, M.; Mendez, J.; Rodriguez-Ortega, M. Biol. Pharm. Bull. 2003,
26, 108e109; (b) Kim, H. K.; Jeon, W. K.; Ko, B. S. Planta Med. 2001, 67, 548e549.
9. (a) Reddy, M. V. B.; Kishore, P. H.; Rao, C. V.; Gunasekar, D.; Caux, C.; Bodo, B. J.
Nat. Prod. 2003, 66, 295e297; (b) Siddikov, G. U.; Yuldashev, M. P.; Aripova, S. F.;
Vdovin, A. D.; Abdullaev, N. D.; Botirov, E. K. Chem. Nat. Compd. 2008, 44,
28e30; (c) Shakil, N. A.; Pankaj; Kumar, J.; Pandey, R. K.; Saxena, D. B. Phyto-
chemistry 2008, 69, 759e764; (d) Asai, T.; Hara, N.; Kobayashi, S.; Kohshima, S.;
Fujimoto, Y. Phytochemistry 2008, 69, 1234e1241.
d
44.6, 78.2, 118.1, 120.7, 121.2, 122.2, 123.6, 127.2, 129.9, 131.9, 136.5,
140.9, 148.6, 160.9, 190.8; EIMS (70 eV) m/z (rel intensity, %) 269
(Mþ, 35), 268 (39), 147 (100), 121 (33), 120 (66), 92 (99), 64 (19), 63
(23). Anal. Calcd for C15H11NO4: C, 66.91; H, 4.12; N, 5.20. Found: C,
66.51; H, 4.20; N, 5.13.
4.1.2.8. 6-Chloro-40-fluoroflavanone (4h). Compound 4h (0.36 g,
82%) was obtained as colorless crystals, mp¼145e146 ꢀC; Rf¼0.31
(ethyl acetate/n-hexane¼1:4); IR (KBr) cmꢁ1:1701 (C]O); 1H NMR
(CDCl3, 400 MHz)
d
2.89 (dd, J¼16.8, 2.8 Hz, 1H, Ha-3), 3.06 (dd,
J¼16.8, 13.2 Hz, 1H, Hb-3), 5.46 (dd, J¼13.2, 2.8 Hz, 1H, H-2), 7.01 (d,
J¼8.4 Hz, 1H, ArH), 7.14 (td, J¼8.8, 2.0 Hz, 2H, ArH), 7.45 (m, 3H,
ArH), 7.89 (d, J¼2.4 Hz, 1H, ArH); 13C NMR (CDCl3, 100 MHz)
d 44.3,
79.1, 115.9 (d, J¼21.2 Hz), 119.8, 121.6, 126.4, 127.3, 128.0 (d,
J¼8.4 Hz), 134.1, 136.1, 159.8, 162.9 (d, J¼246.3 Hz), 190.6; EIMS
(70 eV) m/z (rel intensity, %) 276 (Mþ, 91), 275 (77), 181 (36), 156
(37), 155 (27), 154 (100), 126 (40), 122 (40). Anal. Calcd for
C15H10ClFO2: C, 65.11; H, 3.64. Found: C, 65.05; H, 3.63.
10. Wang, X.; Cheng, S. Catal. Commun. 2006, 7, 689e695.
11. Drexler, M. T.; Amiridis, M. D. J. Catal. 2003, 214, 136e145.
12. Chandrasekhar, S.; Vijeender, K.; Reddy, K. V. Tetrahedron Lett. 2005, 46, 6991e6993.
13. Choudary, B. M.; Ranganath, K. V. S.; Yadav, J.; Kantam, M. L. Tetrahedron Lett.
2005, 46, 1369e1371.
14. Climent, M. J.; Corma, A.; Iborra, S.; Primo, J. J. Catal. 1995, 151, 60e66.
15. (a) Coetzee, J.; Mciteka, L.; Malan, E.; Ferreira, D. Phytochemistry 1999, 52,
737e743; (b) Dutta, C. P.; Roy Lala, P. K. Indian J. Chem. 1975, 13, 425e426.
16. (a) Adams, J. H. J. Org. Chem. 1967, 32, 3992e3998; (b) Brennan, C. M.; Hunt, I.;
Jarvis, T. C.; Johnson, C. D.; McDonnell, P. D. Can. J. Chem. 1990, 68, 1780e1785; (c)
Wurm, G.; Schnetzer, D. Arch. Pharm. (Weinheim) 1992, 325, 717e719; (d) Cha-
turvedi, R.; Patil, P. N.; Mulchandani, N. B. Indian J. Chem. 1992, 31B, 340e341.
17. (a) Climent, M. J.; Garcia, H.; Iborra, S.; Miranda, M. A.; Primo, J. Heterocycles
1989, 29, 115e121; (b) Reichel, L.; Weber, F. G. Pharmazie 1975, 30, 195e198; (c)
Patonay, T.; Litkei, G.; Zsuga, M.; Kiss, A. Org. Prep. Proced. Int. 1984, 16, 315e319.
18. Lee, J. I.; Jung, M. G.; Jung, H. J. Bull. Korean Chem. Soc. 2007, 28, 859e862.
19. Manivel; Rai, P.; Rai, N. P.; Jayashankara, V. P.; Arunachalam, P. N. Tetrahedron
Lett. 2007, 48, 2701e2705.
4.1.2.9. 6-Chloro-40-bromoflavanone (4i). Compound 4i (0.43 g,
80%) was obtained as colorless crystals, mp ¼151e152 ꢀC; Rf¼0.32
(ethyl acetate/n-hexane¼1:4); IR (KBr) cmꢁ1:1689 (C]O); 1H NMR
(CDCl3, 400 MHz)
d
2.89 (dd, J¼16.8, 3.2 Hz, 1H, Ha-3), 3.02 (dd,
J¼16.8, 12.8 Hz, 1H, Hb-3), 5.44 (dd, J¼12.8, 3.2 Hz, 1H, H-2), 7.01 (d,
J¼8.8 Hz, 1H, ArH), 7.35 (m, 2H, ArH), 7.46 (dd, J¼8.8, 2.0 Hz, 1H,
ArH), 7.57 (dd, J¼8.8, 2.0 Hz, 2H, ArH), 7.88 (d, J¼2.4 Hz, 1H, ArH);
13C NMR (CDCl3, 100 MHz)
d 44.2, 79.1, 119.8, 121.6, 122.9, 126.4,
127.4, 127.8, 132.1, 136.1, 137.3, 159.7, 190.4; EIMS (70 eV) m/z (rel
intensity, %) 337 (Mþ, 60), 336 (50), 335 (41), 184 (64), 182 (78), 181
(74), 154 (100), 103 (51). Anal. Calcd for C15H10BrClO2: C, 53.37; H,
2.99. Found: C, 53.47; H, 3.02.
20. The CIF file of crystal 3e has been deposited at the Cambridge Crystallographic
Centre (CCDC), UK, and received the CCDC no. 791334. The X-ray crystallo-
graphic study of 3e is summarized as follows. Crystal data: C15H13BrO3, M¼321.
ꢀ
ꢀ
16, monoclinic system, space group P21/n, a¼5.3393 (1) A, b¼8.5377 (17) A,
3
ꢀ
3
ꢀ
ꢀ
c¼29.789 (6) A, ¼92.52 (3) , V¼1357.0 (5) A , Z¼4, d¼1.572 g/cm . A crystal of
b
dimensions 0.70ꢂ0.42ꢂ0.30 mm was used for measurements on a RIGAKU
4.1.3. General procedure for the preparation of flavanones (4aei)
from o-hydroxyacetophenones (1a,b) and benzaldehydes (2aei) in
one pot. The mixture of 2-hydroxyacetophenones (1a,b)
(10 mmol) and benzaldehydes (2aei) (10 mmol) was stirred, and
then DABCO (3.36 g, 30 mmol) was added. The resulting mixture
was continually stirred and heated to the reflux for 20 h. Then, the
reaction mixture was extracted with CH2Cl2 (3ꢂ50 mL). The
resulting extracts were combined, washed with brine, dried over
anhydrous MgSO4 in sequence. After filtration, the filtrate was
concentrated in vacuo to give crude 4ae, which were further
purified by silica-gel column chromatography (EtOAc/n-
hexane¼1:5). Pure flavanones 4a (67%), 4b (71%), 4c (70%), 4d
AFC7S diffractometer with a graphite monochromator (
u
scans, 2qmax¼45.0o),
ꢀ
Mo K
a
radiation (
l
¼0.71073 A). The total number of independent reflections
measured was 1243, of which 774 were observed (jFj2S2
s
jFj2). The crystal
structure was solved by the direct method and expanded using difference
Fourier techniques, further refined by the program SHEXTL 97 and full-matrix
least-squares calculations. Final indices: Rf¼0.0701, Rw¼0.0819 (w¼1/
[s
2(Fo2)þ(0.1692P)2] where P¼(Fo2þ2Fc2)/3).
21. Mphahlele, M. J.; Fernandes, M. A. S. Afr. J. Chem. 2002, 55, 97e110.
22. Fujise, S.; Fujii, R.; Maeda, T.; Takagi, K.; Nakamura, S. Nippon Kagaku Zasshi
1953, 74, 827e829.
23. Aggarwal, V. K.; Emme, I.; Fulford, S. Y. J. Org. Chem. 2003, 68, 692e700.
24. Chimenti, F.; Fioravanti, R.; Bolasco, A.; Chimenti, P.; Secci, D.; Rossi, F.; Yanez,
M.; Orallo, F.; Ortuso, F.; Alcaro, S.; Cirilli, R.; Ferretti, R.; Sanna, M. L. Bioorg.
Med. Chem. 2010, 18, 1273e1279.
25. Joglekar, S. J.; Samant, S. D. Tetrahedron Lett. 1988, 2, 241e244.