Intramolecular aminolysis of 2-aminochalcone epoxides using InBr 3 or BiCl3 as efficient catalysts

Article abstract of DOI:10.1080/00397911.2011.604571

In the synthesis of aza-flavanone derivatives, several metal halides were screened for their catalytic activity. Among them, BiCl³ and InBr³ catalyze the ring opening of 2-aminochalcone epoxides followed by intramolecular aminolysis

Full text of DOI:10.1080/00397911.2011.604571

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Intramolecular Aminolysis of 2′-
Aminochalcone Epoxides Using InBr3 or
BiCl3 as Efficient Catalysts
Naseem Ahmed a , Harendra Kumar a & B. Venkata Babu a
a Department of Chemistry, Indian Institute of Technology Roorkee,
Roorkee, Uttarakhand, India
Accepted author version posted online: 13 Feb 2012.Version of
record first published: 08 Nov 2012.
To cite this article: Naseem Ahmed , Harendra Kumar & B. Venkata Babu (2013): Intramolecular
Aminolysis of 2′-Aminochalcone Epoxides Using InBr3 or BiCl3 as Efficient Catalysts, Synthetic
Communications: An International Journal for Rapid Communication of Synthetic Organic Chemistry,
43:4, 567-581
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Synthetic Communications1, 43: 567–581, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.604571
INTRAMOLECULAR AMINOLYSIS OF
2’-AMINOCHALCONE EPOXIDES USING InBr3 OR
BiCl3 AS EFFICIENT CATALYSTS
Naseem Ahmed, Harendra Kumar, and B. Venkata Babu
Department of Chemistry, Indian Institute of Technology Roorkee,
Roorkee, Uttarakhand, India
GRAPHICAL ABSTRACT
Abstract In the synthesis of aza-flavanone derivatives, several metal halides were screened
for their catalytic activity. Among them, BiCl3 and InBr3 catalyze the ring opening of
20-aminochalcone epoxides followed by intramolecular aminolysis under mild conditions.
The reactions proceed efficiently at room temperature to afford highly functionalized
2-aryl-3-hydroxy-2,3-dihydro-4-quinolones (aza-flavanones) in excellent yields (82–
92%). Intermolecular aminolysis of 20-aminochalcone epoxides with aniline derivatives
failed under the same catalytic conditions.
Keywords 20-Aminochalcones=epoxides; aminolysis; 2-aryl-3-hydroxy-2,3-dihydro-4-
quinolones; epoxide ring opening; metal halides
INTRODUCTION
2-Aryl-2,3-dihydro-4-quinolones (aza-flavanones) are common structural
intermediates in the biogenesis of naturally occurring flavonoid-type derivatives
and are widely used for the synthesis of medicinal compounds.[1] Derivatives of
2-aryl-4-quinolones and 2-aryl-3-hydroxy-2,3-dihydro-4-quinolones displayed inter-
esting biological properties,[2] such as cytotoxicity against human tumor cell lines,[3]
anticancer activity in the xenograft ovarian OVCAR-3 model, 13% increase in life
span mice,[4] tubulin polymerization inhibition,[5] colchicines binding to tubulin,[6]
hepatoprotective activity, [7] and potential use as scintillator dyes in photo-oxidative
stability.
Received April 6, 2011.
Address correspondence to Naseem Ahmed, Department of Chemistry, Indian Institute of
Technology Roorkee, Roorkee 247667, Uttarakhand, India. E-mail: nasemfcy@iitr.ernet.in
567

568
N. AHMED, H. KUMAR, AND B. V. BABU
Scheme 1. Optimization reaction in synthesis of flavonols.
Different synthetic strategies have been reported for the substituted aza-
flavanones.[1,2] Among them, the Alger–Flynn–Oyamada (AFO) reaction is the most
common approach,[8] in which the treatment of 20-aminochalcones with alkaline
H2O2 at high temperature afforded flavonol and aurone as major and minor pro-
ducts, respectively. In this reaction, the substitution patterns on aromatic rings influ-
ence the rate of the reaction; for example, some substitution patterns of methoxy
[9–11]
group on the aromatic rings gave aurone as major product
and incorporation
of electron-withdrawing groups at C-4 required longer reaction time.[12] Similarly,
elevated temperature and strong alkaline conditions are other drawbacks for many
functional groups present in the molecule. Thus, the product ratio in the AFO reac-
tion depends on the nature of substituents as electron donating or withdrawing and
their substitution pattern on the aromatic rings. Mechanistically, the AFO reaction
follows epoxide intermediate formation.[12–15] Therefore, this reaction is not the right
choice for stereoselectivity toward flavonols. To improve regioselectivity and yields
toward flavonol derivatives, different protic acids were used either as catalyst or pro-
moter, including concentrated HCl, H2SO4, CF3COOH, and AcOH.[16,17] These cat-
alysts or promoters have been used efficiently in many cases. However, the use of
strong acids, high temperature, and prolonged reaction time are major drawbacks,
and the stereoselectivity toward flavonol or aurone remains unresolved. To address
these environmental concerns in chemical synthesis and stereoselectivity calls for
clean and efficient catalytic procedures that can avoid use of harmful catalysts.
In continuation of our interest in Lewis acid catalysis[18–23] and the importance
of metal halides as inexpensive, easily available, and stable catalysts in epoxide ring
opening,[24–29] we report the catalytic properties of various metal salts. Among them,
InBr3 and BiCl3 were found to be excellent catalysts under mild conditions
(Scheme 1, Table 1). The reaction proceeded efficiently at room temperature to
afford highly functionalized 2-aryl-3-hydroxy-2,3-dihydro-4-quinolones in excellent
yield (82–92%). However, intermolecular aminolysis of 20-aminochalcone epoxides
with aniline derivatives failed under same catalytic conditions. In comparison with
other methods, our method gave good yields in shorter reaction time with easy
work-up.
RESULTS AND DISCUSSION
The catalytic efficiency of metal salts is given in Table 1. Entries 1 and 2 (InBr3
and BiCl3) were the most efficient catalysts, which gave optimal yields (92 and 90%,
respectively) at 10 mol% catalyst loading (Tables 1 and 2). Entries 3–10 at 10 mol%

AMINOLYSIS OF 20-AMINOCHALCONE EPOXIDES
569
Table 1. Screening of metal saltsa for the aminolysis of 20-aminochalcone epoxides
Entry
Metal salt
Time (min)
Yield (%)b
1
2
InBr3
BiCl3
45
50
70
40
60
70
55
50
45
65
92
90
60
70
50
50
55
80
65
40
3
MgI2
TaBr5
4
5
NbCl5
ZrCl4
6
7
ZnCl2
InCl3
8
9
10
Anhyd. AlCl3
AlCl3ꢀ6H2O
aGaCl3, SnCl2, ZnO, CuBr2, CeCl3 ꢀ 7H2O, TeCl4, LaCl3, LiBr, AuBr3, and
MgBr2 ꢀ Et2O failed to give products even for longer reaction time.
bYields refer to isolated products 1b in 10 mol% catalyst loading.
catalyst loading gave moderate to good yields (40–70%) along with corresponding
halides (5–10%) as minor products at the C-3 position except for entries 1, 2, and
3 (Table 1). Further increase in catalyst loading gave more side product without
improving the desired product. Some metal salts Listed in the footnote to Table 1
failed to catalyze the reaction even with longer reaction times.
Catalyst optimization is also reported for the most efficient catalyst, InBr3, in
Table 2 for Scheme 1. To optimize the catalyst loading, the reactions were carried
out in 2, 5, 10, and 20 mol% catalyst loadings in dichloromethane at room tempera-
ture, and the efficiency of the catalyst loading was determined from the time needed
for the complete conversion of epoxide. Reactions with InBr3 at 2 and 5 mol% cata-
lyst loading proceeded slowly (2–3 h), whereas at 20 mol% catalyst loading gave the
product along with minor product as 3-bromo-2-phenyl-2,3-dihydroquinolin-4(1H)-
one (7%), which was isolated and characterized by gas chromatography–mass
Spectrometry (GCMS) analysis.
20-Aminochalcones were prepared from 20-aminoacetophenones and aromatic
aldehydes following the reported procedure.[14] Epoxidation of 20-aminochalcones
was carried out with NaOH and H2O2 (30%, wt%) in aqueous tetrahydrofuran
(THF) to afford epoxides in good yields (80–90%) (see the experimental section).
Following a simple experimental procedure, three different types of substituted
20-aminochalcone epoxides (1a–8a, 9a–11a and 12a–16a) were dissolved in dichloro-
methane by stirring, and InBr3 was added in portions and stirred at room
Table 2. Optimization of InBr3 catalyst in Scheme 1
Entry
Catalyst loading (mol%)
Time (h)
Yield (%)
1
2
3
4
2
5
10
7
55
65
10
20
0.7–0.8
2–3
92
80 þ 7a
aSide product 3-bromo-2-phenyl-2,3-dihydroquinolin-4(1H)-one (7%).

570
N. AHMED, H. KUMAR, AND B. V. BABU
temperature for 45–50 min. After usual workup, 2-aryl-3-hydroxy-2,3-dihydro-4-qui-
nolones 1b–16b was obtained in 82–92% yields (Scheme 2, Table 3).
The assigned structures of 20-aminochalcone epoxides 1a–16a and products 1b–
1
16b were confirmed on the basis of their spectral analysis [infrared (IR), H and
13CNMR, and GC-MS=HRMS]. The products were further compared with available
data in the literature.[30] The trans-stereochemistry of epoxides 1a–16a was confirmed
by the coupling constants of the a- and b-protons. For example, 3a, in the 1H NMR
(500 MHz) data [d (ppm): 4.23 (d, J ¼ 2.0 Hz, b-H, 1H), 4.03 (d, J ¼ 2.0 Hz, a-H,
1H)], the J values (2 Hz) indicate a trans-substituted epoxide. The cis-configuration
of 2-aryl-3-hydroxy-2,3-dihydro-4-quinolones 1b–16b was confirmed by the coupling
constants of their a - and b-protons. For example, 3b, in the 1H NMR data
[(500 MHz) d (ppm): 5.26 (d, J ¼ 3.0 Hz, b-H, 1H), 5.51 (d, J ¼ 3.0 Hz, a-H, 1H)],
the J values (3 Hz) indicate a cis-configuration. Similarly, substituted 3-hydroxy-1-
acetyl-2,3-dihydroquinolin-4(1H)-ones, for example, 14b, were also comfirmed on
1
the basis of H NMR data for their cis-configuration (Table 4, Fig. 1). 20-Amino
and 20-amide chalcones were followed the plausible reaction path as shown in
Scheme 3. The enhanced stereoselectivity and good yield for flavonols under acidic
conditions might be due to the b-carbon possessing considerable cationic character
at the benzylic position and therefore being resonance stabilized. The cis-
configuration in 2-aryl-3-hydroxy-2,3-dihydro-4-quinolones further support benzylic
resonance stabilization, which results in a SN1-like mechanism instead of a SN2-type
mechanism in basic conditions (Scheme 3).
We also subjected 20-hydroxychalcone epoxide analogs to the same reaction
conditions which resulted in poor yields (10–20%) even after 2–5 h. This lack of reac-
tivity might be due to the low nucleophilicity of oxygen in 20-hydroxychalcone epox-
ides as compared to the amino nitrogen in 20-aminochalcone epoxides. To establish
broader catalytic efficiency in the synthesis of aza-flavanones, primary and second-
ary amines were also tested for their nucleophilicity. The yields were not very
Scheme 2. Inter- and intramolecular aminolysis of chalcone epoxides.

AMINOLYSIS OF 20-AMINOCHALCONE EPOXIDES
571
Table 3. Intramolecular aminolysis of 20-aminochalcone epoxidesa,b
Entry
Epoxychalcone
Product
Yield (%)c
1
92
2
3
4
5
88
90
92
85
6
88
(Continued )

572
N. AHMED, H. KUMAR, AND B. V. BABU
Table 3. Continued
Entry
Epoxychalcone
Product
Yield (%)c
7
85
8
89
82
85
9
10
11
85
12
87
(Continued )

AMINOLYSIS OF 20-AMINOCHALCONE EPOXIDES
573
Table 3. Continued
Entry
Epoxychalcone
Product
Yield (%)c
13
89
83
86
90
14
15
16
aAll reactions were carried out according to the general procedure.
bReaction time: 45–50 min at room temp. in all entries.
cYields refer to isolated products with InBr3 catalyst (10 mol%).
different in both cases; however, primary amines were better nucleophiles than sec-
ondary amines 12b–16b, perhaps due to steric and electronic factors (Table 3).
Under
a
solid-supported reaction, 20-aminochalcone epoxides and
20-hydroxychalcone epoxides were adsorbed on solid-supported catalysts (InBr3–
silica gel and BiCl3–silica gel) and stirred at room temperature to elevated tempera-
ture, but failed to give the flavonols.
Similarly, the intermolecular epoxide ring-opening reactions were shown with
aniline derivatives under these catalytic conditions, which failed to give the product
17 (Scheme 2).

574
N. AHMED, H. KUMAR, AND B. V. BABU
Table 4. 1H and 13C NMR data for compounds 3b and 14b
3b
14b
1H-
-NH
2
3b (d, ppm)
1H
14b (d, ppm)
13C
(d, ppm) (d, ppm)
6.31 (s, br, D2O-
exchangeable)
5.26 (d, J ¼ 3.0 Hz,
1H)
—
—
—
2
3
5.07 (d, J ¼ 4.0 Hz,
1H)
2
3
4
63.05
76.11
197.18
126.32
58.25
75.03
198.28
128.55
3
5.51 (d, J ¼ 3.0 Hz,
1H)
5.31 (d, J ¼ 4.5 Hz,
1H)
-OH
3.70 (s, br,D2O-
exchangeable)
6.70–7.67(m, 8H)
Ar-5
8.31 (d, J1 ¼ 8.0 Hz,
1H)
7.22 (m, 2H)
Ar-5,6,7,8
and Ar0-
20,30,40,50
Ar-6,8
Ar 5
Ar-7
-OH
7.58 (m, 1H)
3.89 (s, br, D2O-
exchngeble)
Ar 6
Ar 7
116.03
130.98
119.26
131.20
-CH3
2.15 (s, 3H)
3.45 (s, 3H)
7.32 (m, 2H)
7.41 (m, 2H)
Ar 8
Ar-C
117.15
151.00
122.94
—
115.59
151.71
117.49
168.92
23.96
-OCH3
Ar0-20,60
Ar0-30,50
Ar-C
-COCH3
-CH3
—
—
-OCH3
Ar010
Ar020,60
Ar030,50
Ar040
61.05
136.20
128.74
129.11
128.06
135.78
127.45
115.24
159.18
CONCLUSION
In conclusion, we have reported the catalytic properties of metal halides in the
synthesis of 2-aryl-3-hydroxy-2,3-dihydro-4-quinolones. BiCl3 and InBr3 were
explored as mild and efficient catalysts for the regioselective ring opening and intra-
molecular aminolysis of 20-aminochalcone epoxides at room temperature. To the
best of our knowledge, InBr3 and BiCl3 had not been studied in this capacity before
and therefore are novel subjects for investigation.
Figure 1. Protected and unprotected 3-hydroxy-dihydroquinolines of 3b and 14b.

AMINOLYSIS OF 20-AMINOCHALCONE EPOXIDES
575
Scheme 3. Plausible mechanism with InBr3(10 mol%).
EXPERIMENTAL
Organic solvents were dried by standard methods when necessary. Commer-
cially available reagents were used without further purification unless mentioned.
Aniline was freshly distilled under reduced pressure prior to use. All reactions were
monitored by thin-layer chromatography (TLC) using precoated silica-gel aluminum
plates. Visualization of TLC plates was accomplished with ultraviolet (UV) lamp or
in an iodine chamber. Column chromatography was performed using silica gel
(100–200 mesh) (SD Fine-Chem Limited) with ethyl acetate = hexanes as an eluent
system. Melting points were recorded on Perfit apparatus and are uncorrected.
The IR spectrum was recorded with KBr on a Thomso Nicolet Fourier transform
(FT)–IR spectrophotometer. IR spectra of the compounds were expressed as wave
1
numbers (cmꢁ1). H and 13C NMR spectra were obtained in CDCl3 on a Bruker
Spectrospin-500=125 MHz spectrometer using tetramethylsilane (TMS) as internal
1
standard. Chemical shifts of H NMR spectra were given in parts per million with
respect to TMS, and the coupling constant J was measured in hertz (Hz). Data
are reported as follows: chemical shifts, multiplicity (s ¼ singlet, d ¼ doublet,
t ¼ triplet, q ¼ quartet, m ¼ multiplet, dd ¼ double doublet, br ¼ broad). Mass spec-
tra were recorded on Perkin-Elmer Clarus-500 instrument (EI, 70 eV) as GC-MS.
HR-MS spectra were recorded on Bruker instruments.
General Procedure: Synthesis of 2’-Aminochalcone Epoxides
Aqueous NaOH (5 M, 10 ml) was added dropwise to a stirred solution of
20-aminochalcones (18 mmol) in aqueous THF (30 ml, H2O–THF, 1:2 ratio) and
further stirred for 10 min. Then, H2O2 (15 ml, 30% wt%) was added dropwise and
further stirred for 6–7 h at room temperature. With TLC monitoring, the reaction
mixture was poured in H2O. The resulting precipitate was filtered, washed with
water, and dried under reduced pressure. The product was recrystallized in EtOH
or silica-gel column chromatography in petroleum ether–CH2Cl2 as eluent to give
the products in 80–90% yield.

576
N. AHMED, H. KUMAR, AND B. V. BABU
Selected Spectral Data
(2-Aminophenyl)(3-(4-chlorophenyl)oxiran-2-yl)methanone 3a (Table 2).
Yield: 88%. White solid, mp: 120–125 ꢂC. 1H NMR (CDCl3, 500 MHz): d
7.70–7.69 (dd, J1 ¼ 1.5 Hz, J2 ¼ 1.0 Hz, 1H), 7.38–7.36 (m, 2H), 7.33–7.29 (m, 3H),
6.71–6.69 (dd, J1 ¼ 1.5 Hz, J2 ¼ 1.0 Hz, 1H), 6.65–6.61 (m, 1H), 6.33 (s, br, D2O
exchangeable), 4.23 (d, J ¼ 2 Hz, 1H), 4.03 (d, J ¼ 2 Hz, 1H). 13C NMR (CDCl3,
125 MHz): d 193, 151, 135.36 135, 134, 130, 129, 127, 117, 116.74, 116, 61, 58. IR
(KBr) cmꢁ1: 3443, 3321, 1640, 1545, 1483, 1228, 1161, 1087, 1017, 901, 807, 752,
648. GC-MS (m=z): 273 [Mþ., C15H12ClNO2], 257, 244, 220, 207, 165, 145, 132
(100), 120, 105, 91, 77, 65.
(2-Aminophenyl)-3-(4-bromophenyl-oxiran-2-yl)methanone 4a (Table 2).
Yield: 86%. White solid, mp: 130–134 ꢂC. 1H NMR (CDCl3, 500 MHz): d
7.69–7.67 (dd, J1 ¼ 3.5 Hz, J2 ¼ 4.5 Hz, 1H), 7.53–7.52 (m, 1H), 7.32–7.29 (m, 1H),
7.25 (dd, J1 ¼ 2.0 Hz, J2 ¼ 4.5 Hz, 3H), 6.70–6.68 (dd, J1 ¼ 1.0 Hz, J2 ¼ 0.5 Hz, 1H),
6.64–6.61 (m, 1H), 6.33 (s, br, D2O exchangeable), 4.23 (d, J ¼ 1.5 Hz, 1H), 4.00
(d, J ¼ 2.0 Hz, 1H). 13C NMR (CDCl3, 125 MHz): d 192.95, 150.85, 135.39,
134.90, 132.02, 131.96, 130.37, 122.95, 117.42, 116.69, 116.15, 60.92, 58.48. IR
(KBr) cmꢁ1: 3445.44, 3321.68, 1642.48, 1547.33, 1393.34, 1228.51, 1160.11,
1067.15, 899.62, 800.22, 751.78, 659.71. GC-MS (m=z): 317 [Mþ., C15H12BrNO2],
300, 288, 264, 219, 146, 132(100), 125, 120, 91, 77, 65.
(2-Amino-5-bromo-phenyl)-(3-phenyl-oxiranyl)-methanone 9a (Table 2).
1
Yield: 82%. H NMR (CDCl3, 500 MHz): d 7.72 (d, J1 ¼ 1.5 Hz, 1H), 7.34–7.38
(m, 5H), 7.21–7.19 (dd, J1 ¼ 2.0, J2 ¼ 1.5, 1H), 6.59 (d, 1H), 6.32 (s, br, D2O
exchangeable), 4.32 (d, J ¼ 2 Hz, 1H), 4.10 (d, J ¼ 2 Hz, 1H). 13C NMR (CDCl3,
125 MHz): d 193.11, 149.82, 138.84, 135.27, 130.49, 129.95, 128.78, 125.85, 118.39,
116.80, 114.08, 61.62, 59.51. IR (KBr) cmꢁ1: 3445.37, 3325.03, 1640.76, 1500.48,
1218.79, 1158.54, 1020.35, 890.16, 801.67, 746.75, 694.39, 654.37. GC-MS (m=z):
318 [Mþ., C15H12BrNO2].
(2-Amino-5-bromo-phenyl)-[3-(4-fluoro-phenyl)-oxiranyl]-methanone
10a (Table 2). Yield 85%. White solid, mp: 120–123 ꢂC. 1H NMR (CDCl3,
500 MHz): d 7.69 (d, J ¼ 1.5 Hz, 1H), 7.53–7.52 (dd, J1 ¼ 1.5, J2 ¼ 1.0, 1H), 7.32
(d, 2H), 7.25 (d, 2H), 6.70 (d, 1H), 6.33 (s, br, D2O exchangeable), 4.22 (d,
J ¼ 1.5 Hz, 1H), 4.09 (d, J ¼ 2.0 Hz, 1H). 13C NMR (CDCl3, 125 MHz): d 192.95,
150.85, 135.39, 134.90, 132.02, 131.96, 130.37, 122.95, 117.42, 116.69, 116.15,
60.92, 58.48. IR (KBr) cmꢁ1: 3448.44, 3325.68, 1640.48, 1549.30, 1392.35, 1223.55,
1165.11, 1065.15, 898.62, 800.22, 751, 659. HR-MS (m=z): 335 [Mþ.,
C15H11BrFNO2].
2-(N-Acetylaminophenyl)-3-phenyl-oxiran-2-yl-methanone 12a (Table 2).
White solid. Yield: 69%. 1H NMR (CDCl3, 500 MHz): d 11.36 (s, br, D2O exchange-
able 1H), 8.56 (d, J1 ¼ 8.0 Hz, 1H), 7.81 (dd, J1 ¼ 8.0 Hz, J2 ¼ 1.5 Hz, 1H), 7.62 (m,
1H), 7.57 (m, 3H), 7.28 (m, 3H), 4.30 (d, J ¼ 2.0 Hz, 1H), 4.06 (d, J ¼ 2.0 Hz, 1H),
2.26 (s, 3H). 13C NMR (CDCl3, 125 MHz): d 194.51, 168.95, 149.95, 135.97,
134.05, 131.99, 129.85, 127.05, 123.09, 122.31, 121.05, 120.56, 61.35, 59.12, 25.49.

AMINOLYSIS OF 20-AMINOCHALCONE EPOXIDES
577
IR (KBr) cmꢁ1: 3359, 3078, 1669, 1639, 1582, 1411, 1356, 1233, 754. GC-MS (m=z):
281 [Mþ., C17H15NO3].
2-(N-Acetylaminophenyl)-3-(4-methoxyphenyl)-oxiran-2-yl-methanone
14a (Table 2). White solid. Yield: 61%. 1H NMR (CDCl3, 500 MHz): d 11.31 (s, br,
D2O exchangeable 1H), 8.75 (d, J1 ¼ 8.0 Hz, 1H), 7.77 (dd, J1 ¼ 8.0 Hz, J2 ¼ 1.5 Hz,
1H), 7.55 (m, 1H), 7.41 (m, 1H), 7.21 (m, 4H), 4.29 (d, J ¼ 2.0 Hz, 1H), 4.07 (d,
J ¼ 2.0 Hz, 1H), 3.49 (s, 3H) 2.22 (s, CH3). 13C NMR (CDCl3, 125 MHz): d
195.46, 169.84, 159.11, 140.45, 134.21, 133.51, 132.38, 127.90, 126.29, 124.07,
123.16, 121.41, 75.64, 61.93, 59.25, 24.04. IR (KBr) cmꢁ1: 3345, 3025, 2928, 1682,
1630, 1591, 1459, 1399, 1233, 1130, 1007, 823. GC-MS (m=z): 311 [Mþ., C18H17NO4].
General Procedure: Synthesis of 3-Hydroxy-aza-flavonone
Derivatives
20-Aminochalcone epoxides (2.5 mmol) were dissolved in dichloromethane
(10 mL) by stirring, and indium bromide (0.25 mmol, 10 mol%) was added in por-
tions and stirred for 45–50 min at room temperature. The reaction mixture was
extracted with CH2Cl2 by adding water. The organic layer was dried (anhydrous
Na2SO4), filtered, and evaporated under reduced pressure to obtain the pure product
or purified by flash column chromatography on silica gel using hexane–CH2Cl2 (8:2)
as eluent to afford the products.
Selected Spectral Data
cis-3-Hydroxy-2-phenyl-2,3-dihydroquinolin-4(1H)-one 1b (Table 2).
1
Yields: 92%. H NMR (CDCl3, 500 MHz): d 3.67 (s, br, D2O-exchangeable), 5.10
(d, J ¼ 5 Hz, 1H), 5.38 (d, J ¼ 5 Hz, 1H), 6.33 (s, br, D2O-exchangeable), 6.72–7.71
(m, 9H). 13C NMR (CDCl3, 125 MHz): d 196.48, 152.42, 137.90, 135.07, 133.75,
128.85, 127.77, 126.96, 126.63, 123.75, 119.28, 74.52, 63.43. IR (KBr) cmꢁ1
:
3480.11, 3350.11, 1675.55, 1617.55, 1479.79, 1369.59, 1310.63, 1253.61, 1102.28,
974.42, 754.17, 701.16. GC-MS (m=z): 239 [Mþ, C15H13NO2]: 220, 190, 148 (100),
130, 120, 91, 77, 65, 51. HR-MS (m=z) for C15H13NO2 calcd. 239.0946; found:
239.0940. GC purity: 94%.
cis-3-Hydroxy-2-p-tolyl-2,3-dihydroquinolin-4(1H)-one 2b (Table 2).
Yields: 88%. 1H NMR (CDCl3, 500 MHz): d 2.45 (s, 3H), 3.70 (s, br,
D2O-exchangeable), 5.25 (d, J ¼ 3 Hz, 1H), 5.50 (d, J ¼ 3 Hz, 1H), 6.32 (s, br,
D2O-exchangeable), 6.52–7.7 (m, 8H). 13C NMR (CDCl3, 125 MHz): d 197, 152,
136, 132, 129, 128.74, 128.27, 126.15, 123.61, 117.60, 116.40, 76.03, 62.92, 22.06.
IR (KBr) cmꢁ1: 3478.01, 3359.15, 2922.44, 1687.08, 1611.14, 1488.32, 1407.29,
1311.25, 1260.80, 1160.45, 1094.38, 1016.09, 973.8, 752.56. GC-MS (m=z): 253
[Mþ, C16H15NO2]; 254, 193, 165, 148(100), 125, 119, 91, 77, 65, 51. HR-MS (m=z)
for C16H15NO2 calcd. 253.1103; found: 253.1092. GC purity: 90%.
cis-2-4-Chlorophenyl-3-hydroxy-2,3-dihydroquinolin-4(1H)-one 3b
(Table 2). Yield: 90%. 1H NMR (CDCl3, 500 MHz): d 3.70 (s, br, D2O-
exchangeable), 5.26 (d, J ¼ 3 Hz, 1H), 5.51 (d, J ¼ 3 Hz, 1H), 6.31 (s, br,

578
N. AHMED, H. KUMAR, AND B. V. BABU
D2O-exchangeable), 6.70–7.67 (m, 8H). 13C NMR (CDCl3, 125 MHz): d 197, 151,
136, 131, 129, 128.74, 128, 126, 123, 117, 116, 76, 63. IR (KBr) cmꢁ1: 3478, 3359,
2922, 1687, 1611, 1488, 1407, 1311, 1261, 1160, 1094, 1016, 974, 752. GC-MS (m=
z): 273 [Mþ, C15H12ClNO2], 257, 254, 193, 165, 148 (100), 125, 119, 91, 77, 65, 51.
HR-MS (m=z) for C15H12ClNO2 calcd. 273.0557; found: 273.0550. GC purity: 92%.
cis-2-(4-Bromophenyl)-3-hydroxy-2,3-dihydroquinolin-4(1H)-one 4b
(Table 2). Yield: 92%.1H NMR (CDCl3, 500 MHz): d 4.51 (s, br, D2O-
exchangeable), 5.25 (d, J ¼ 3 Hz, 1H), 5.51 (d, J ¼ 3.5 Hz, 1H), 6.34 (s, br, D2O-
exchangeable), 6.71–7.67 (m, 8H). 13CNMR (CDCl3, 125 MHz): d 196.7, 151.18,
132.37, 131.91, 130.28, 129.46, 125.69, 122.89, 120.91, 115.81, 114.38, 75.96, 62.45.
IR (KBr) cmꢁ1: 3480.53, 3359.30, 2921.87, 1687.58, 1484.38, 1408.10, 1313.71,
1257.51, 1099.52, 1072.58, 1009.65, 749.24 and 702.48. GC-MS (m=z): 317 [Mþ.,
C15H12BrNO2], 196, 139, 105, 91, 77, 65, 51. HRMS (m=z) for C15H12BrNO2 calcd.
317.0051; found: 317.0042. GC purity: 93%.
cis-3-Hydroxy-2-(4-methoxyphenyl)-2,3-dihydroquinolin-4(1H)-one 5b
(Table 2). Yields: 85%.1H NMR (CDCl3, 500 MHz): d 3.53 (s, 3H), 3.56 (s, br,
D2O-exchangeable), 4.48 (d, J ¼ 3.0 Hz, 1H), 4.81 (d, J ¼ 3.5 Hz, 1H), 6.26 (s, br,
D2O-exchangeable), 6.70–7.87 (m, 8H). 13CNMR (CDCl3, 125 MHz): d 198.9,
160.02, 151.51, 136.16, 130.30, 127.94, 127.85, 118.64, 116.35, 115.66, 114.30,
75.64, 64.17, 55.38. IR (KBr) cmꢁ1: 3480.11, 3350.30, 2924.02, 1665.22, 1610.08,
1512.69, 1478.26, 1400.03, 1248.49, 1177.61, 1095.47, 1026.09, 985.95, 755.09,
615.91. GC-MS (m=z): 269 [Mþ, C16H15NO2]; 255, 208, 180, 165, 152, 148,
121(100), 106, 102, 91, 77, 65, 51. HR-MS (m=z) for C16H15NO3 calcd. 269.1052;
found: 269.1048. GC purity: 89%.
cis-6-Bromo-3-hydroxy-2-phenyl-2,3-dihydroquinolin-4(1H)-one 9b
(Table 2). Yield: 82%. 1H NMR (CDCl3, 500 MHz): d 3.82 (s, br D2O-
exchangeable), 5.02 (d, J ¼ 5 Hz, 1H), 5.38 (d, J ¼ 5.5 Hz, 1H), 6.30 (s, br, D2O-
exchangeable), 6.72–7.71 (m, 8H). 13CNMR (CDCl3, 125 MHz): d 197.48, 150.32,
137.90, 135.07, 128.95, 128.85, 127.97, 127.16, 126.63, 120.75, 119.28, 74.52, 63.43.
IR (KBr): cmꢁ1 3485.11, 3355.11, 1680.55, 1620.55, 1480.79, 1370.59, 1315.63,
1250.61, 1112.28, 979.42, 754.17, 701.16. GC-MS (m=z): 318 [Mþ., C15H12BrNO2].
HRMS (m=z) for C15H12BrNO2 calcd. 317.0051; found: 317.0042. GC purity: 91%.
cis-6-Bromo-2-(4-fluorophenyl)-3-hydroxy-2,3-dihydroquinolin-4(1H)-
1
one 10b (Table 2). Yield: 85%. H NMR (CDCl3, 500 MHz): d 3.75 (s, br, D2O-
exchangeable), 5.28 (d, J ¼ 3 Hz, 1H), 5.50 (d, J ¼ 3 Hz, 1H), 6.32 (s, br, D2O-
exchangeable), 6.70–7.66 (m, 7H). 13CNMR (CDCl3, 125 MHz): d 197.80, 160.11,
149.11, 138.94, 135.63, 130.38, 128.74, 128.27, 123.07, 117.60, 116.40, 75.89, 62.88.
IR (KBr) cmꢁ1: 3479.01, 3350.15, 2911.44, 1690.08, 1619.14, 1485.32, 1412.29,
1318.25, 1256.80, 1167.45, 1099.38, 1019.09, 973.8, 760.56. GC-MS (m=z): 335
[Mþ., C15H11BrFNO2]. HR-MS (m=z) for C15H11BrFNO2 calcd. 334.9957; found:
334.9853. GC purity: 93%.
cis-6-Bromo-3-hydroxy-2-(4-methoxyphenyl)-2,3-dihydroquinolin-4(1H)-
1
one 11b (Table 2). Yields: 85%. H NMR (CDCl3, 500 MHz): d 3.69 (s, 3H), 3.89
(s, br, D2O-exchangeable), 5.22 (d, J ¼ 3.0 Hz, 1H), 5.43 (d, J ¼ 3.5 Hz, 1H), 6.28

AMINOLYSIS OF 20-AMINOCHALCONE EPOXIDES
579
(s, br, D2O-exchangeable), 6.70–7.87 (m, 7H). 13CNMR (CDCl3, 125 MHz): d
198.98, 159.02, 149.51, 136.16, 131.30, 127.94, 127.85, 119.64, 117.35, 115.66,
114.30, 75.64, 64.17, 55.38. IR (KBr) cmꢁ1: 3485.11, 3349.30, 2924.02, 1670.22,
1612.08, 1519.69, 1480.26, 1422.03, 1250.49, 1177.61, 1095.47, 1026.09, 985.95,
755.09, 615.91. GC-MS (m=z): 347 [Mþ., C16H14BrNO3]. HR-MS (m=z) for
C16H14BrNO3 calcd. 347.0157; found: 347.0150. GC purity: 92%.
cis-3-Hydroxy-1-acetyl-2-phenyl-2,3-dihydroquinolin-4(1H)-one 12b
1
(Table 2). Yellowish solid. Yield: 90%. H NMR (CDCl3, 500 MHz): d 8.10 (d,
J1 ¼ 8.0 Hz, 1H), 7.61 (m, 2H), 7.45 (m, 2H), 7.32 (m, 2H), 7.19 (m, 2H) 5.36 (d,
J ¼ 5.0 Hz, 1H), 5.09 (d, J ¼ 4.0 Hz, 1H), 3.90 (s, br, D2O exchngeble), 2.21 (s,
3H). 13C NMR (CDCl3, 125 MHz): d 196.35, 169.94, 152.35, 137.87, 134.92,
133.68, 128.69, 127.65, 126.79, 126.49, 123.59, 119.17, 70.21, 55.94, 25.41. IR
(KBr) cmꢁ1: 3305, 3071, 1662, 1621, 1585, 1407, 1351, 1245, 754. GC-MS (m=z):
281 [Mþ., C17H15NO3] 281. HR-MS (m=z) for C17H15NO3 calcd. 281.1052; found:
281.1045. GC purity: 91%.
cis-2-(4-Bromophenyl)-3-hydroxy-1-acetyl-2,3-dihydroquinolin-4(1H)-
1
one 13b (Table 2). Yellow solid. Yield: 91%. H NMR (CDCl3, 500 MHz): d 8.24
(d, J1 ¼ 8.0 Hz, 1H), 7.73 (m, 2H), 7.55 (m, 1H), 7.44 (m, 2H), 7.24 (m, 2H), 5.46 (d,
J ¼ 5.0 Hz, 1H), 5.19 (d, J ¼ 4.0 Hz, 1H), 4.13 (s, br, D2O exchangeable), 2.19 (s, 3H).
13C NMR (CDCl3, 125 MHz): d 197.92, 169.29, 151.05, 132.25, 131.85, 130.17,
129.39, 125.57, 122.81, 120.89, 115.76, 114.29, 69.15, 61.05, 25.48. IR (KBr) cmꢁ1
:
3426, 2995, 2935, 1668, 1632, 1591, 1417, 1395, 1282, 1170, 1092, 650. GCMS
(m=z): 359 [Mþ., C17H14BrNO3]. HR-MS (m=z) for C17H14BrNO3 calcd. 359.0157;
found: 359.0148. GC purity: 94%.
cis-2-(4-Methoxyphenyl)-3-hydroxy-1-acetyl-2,3-dihydroquinolin-4(1H)-
1
one 14b (Table 2). Yellowish solid. Yield: 83%. H NMR (CDCl3, 500 MHZ): d
8.31 (d, J1 ¼ 8.0 Hz, 1H), 7.58 (m, 1H), 7.41 (m, 2H), 7.32 (m, 2H), 7.22 (m, 2H)
5.31 (d, J ¼ 5.0 Hz, 1H), 5.07 (d, J ¼ 4.0 Hz, 1H), 3.89 (s, br, D2O exchangeble),
3.45 (s, 3H) 2.15 (s, 3H). 13C NMR (CDCl3, 125 MHz): d 198.28, 168.92, 159.18,
151.71, 135.78, 131.20, 128.55, 127.45, 119.26, 117.49, 115.59, 115.24, 75.03, 61.05,
58.25, 23.96. IR (KBr): cmꢁ1 3440, 2959, 2920, 1666, 1632, 1596, 1406, 1336,
1233, 1125, 1091, 771. GC-MS (m=z): 311 [Mþ., C18H17NO4]. HRMS (m=z) for
C18H17NO4 calcd. 311.1158; found: 311.1151. GC purity: 90%.
cis-2-(4-Chlorophenyl)-3-hydroxy-1-acetyl-2,3-dihydroquinolin-4(1H)-
one 16b (Table 2). Yellow solid. Yield: 92%. 1H NMR (CDCl3, 500 MHz): d 8.21
(d, J1 ¼ 8.0 Hz, 1H), 7.69 (m, 1H), 7.50 (m, 2H), 7.39 (m, 2H), 7.25 (m, 2H) 5.39 (d,
J ¼ 5.0 Hz, 1H), 5.15 (d, J ¼ 4.0 Hz, 1H), 4.01 (s, br, D2O exchngeble), 2.15 (s, 3H).
13C NMR (CDCl3, 125 MHz): d 198.04, 170.10, 159.91, 136.15, 133.79, 132.95,
131.20, 130.85, 129.45, 126.92, 124.99, 123.55, 72.95, 59.89, 24.98. IR (KBr) cmꢁ1
:
3338, 2922, 2895, 1665, 1627, 1591, 1395, 1281, 1171, 1089, 756. GCMS (m=z):
315 [Mþ., C17H14ClNO3]. HR-MS (m=z) for C17H14ClNO3 calcd. 315.0662; found:
315.0655. GC purity: 95%.

580
N. AHMED, H. KUMAR, AND B. V. BABU
ACKNOWLEDGMENTS
This work was financially supported by the Indian Institute of Technology
Roorkee through Ministry of Human Resource Development (MHRD), New Delhi.
B. V. B. and H. K. thank MHRD for the award of fellowships. The reviewers are
highly appreciated for their valuable suggestions.
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