Intramolecular Friedel-Crafts alkylation of chalcone epoxides using indium(III) chloride as an efficient catalyst

Article abstract of DOI:10.1055/s-0030-1260091

Indium(III) chloride catalyzes the ring opening of chalcone epoxides followed by intramolecular Friedel-Crafts alkylation under mild conditions at room temperature to afford highly functionalized 3-aryl-2-hydroxy-2,3-dihydro- 1H-inden-1-ones in excellent yields (81-95%). Georg Thieme Verlag Stuttgart, New York.

Full text of DOI:10.1055/s-0030-1260091

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PAPER
2471
Intramolecular Friedel–Crafts Alkylation of Chalcone Epoxides Using
Indium(III) Chloride as an Efficient Catalyst
S
ynthesis of 2-Hyd
a
roxyindan-
s
1-one
D
e
e
rivatives em Ahmed,* B. Venkata Babu, Harendra Kumar
Department of Chemistry, Indian Institute of Technology, Roorkee 247 667, Uttarakhand, India
Fax +91(1332)285745; E-mail: nasemfcy@iitr.ernet.in
Received 6 April 2011; revised 24 May 2011
cess,14 palladium-catalyzed Heck and Negishi cycliza-
tion,14a,b and ring-closing metathesis.15 Different Lewis
acids catalyze this reaction, for example, TFA, SbF5,16a
AlCl3,16b TiCl4,17 PPA,18 MsOH,19 HF,20 P2O5,21 TFAA,22
and perfluorinated sulfonic acid resin (Nafion-H).23 The
Friedel–Crafts reaction calls for high temperatures or
highly acidic conditions and catalytic enantioselective
Negishi reaction of indanones requires multistep synthe-
sis of 3-substituted indanones and suffers from high cata-
lyst loading.5
Abstract: Indium(III) chloride catalyzes the ring opening of chal-
cone epoxides followed by intramolecular Friedel–Crafts alkylation
under mild conditions at room temperature to afford highly func-
tionalized 3-aryl-2-hydroxy-2,3-dihydro-1H-inden-1-ones in excel-
lent yields (81–95%).
Key words: indium(III) chloride, intramolecular Friedel–Crafts
alkylation, chalcones epoxides, epoxide ring opening, 2,3-dihydro-
1H-inden-1-ones
Indan-1-one and indan-2-one derivatives constitute the
core structures of many natural products, agrochemicals,
and medicines1 including indacrinone,1a–c indanoyl isole-
ucine conjugates,1d and indanocines.1e 2-(Alkoxycarbon-
yl)- and 2-acetylindan-1-ones are present in the cytotoxic
natural compounds pterosines,1,2 the potent and selective
COX-2 inhibitor flosulide2,3 and the acetylcholinesterase
inhibitor donepezil hydrochloride,4 used for the treatment
of Alzheimer’s disease.3 They are also used as intermedi-
ates in the synthesis of norditerpene taiwaniaquinol B,5
Cl
O
O
Cl
Ph
R
HO2C
R = Me, OH, OAc
(+)-indacrinone
O
MeO
MeO
NBn⋅HCl
donepezil hydrochloride (Aricept®)
sulindac,5a
a
nonsteroidal anti-inflammatory drug
(NSAID),4a–c and have shown ligand properties for impor-
tant receptors, such as NMDA receptor antagonists,4d ben-
zodiazepines,4e melatonin precursor,4f and glutamate
subtype-2 receptor (Figure 1).4g Enantiomerically pure
derivative, 1-aminoindan-2-ol is a key precursor of the
chiral ligand and the chiral auxiliary in the asymmetric
synthesis of Indinavir, a potent inhibitor of the protease of
human immunodeficiency virus (HIV).6 Baeyer–Villiger
oxidation of indan1-ones gives biologically active cou-
marins, for example, 3,4-dihydro-4-arylcoumarins
(neoflavonoids) present in natural product calomelanols.7
Diacetoxydihydrocoumarin and natural dihydrocou-
marins (DHC) are of great interest in the flavor industry8
and precursors for the synthesis of important bioactive
compounds Detrol LA (tolterodine tartrate), a muscarine
receptor antagonist used for the treatment of urinary blad-
der disorder.9
OH
O
O
i-Pr
H
HO
MeO
R
OH
taiwaniaquinol B
R = H, pterosine B
R = OH, pterosine C
Figure 1 Bioactive indan-1-one derivatives
24
In continuation of our interest in Lewis acid catalysis
and the importance of metal halides as inexpensive, easily
available, and stable catalysts in epoxide ring opening.25
Herein, we report the catalytic properties of metal halides
in the synthesis of highly functionalized 2-hydroxyindan-
1-one derivatives at room temperature (Scheme 1,
A number of synthetic approaches have been reported for
the synthesis of indan-1-ones, for example, intramolecu-
lar Friedel–Crafts alkylation,10 Nazarov cyclization11 an-
Cl
Cl
Cl
Cl
catalyst
nulation
methodology,12
tandem
Knoevenagel
O
CH2Cl2, r.t.,
3–24h
condensation–cycloalkylation,13 photochemical pro-
OH
O
O
5–95%
2a
1a
SYNTHESIS 2011, No. 15, pp 2471–2477
x
x.
x
x
.
2
0
1
1
Advanced online publication: 08.07.2011
DOI: 10.1055/s-0030-1260091; Art ID: Z36711SS
Scheme 1
© Georg Thieme Verlag Stuttgart · New York

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PAPER
1
Table 1). In comparison with other methods, our method tral analysis (IR, H and 13C NMR, and GC–MS/EI MS)
gave high yields in a shorter reaction time (4–5 h), and and also compared with reported data in the literature.7b
with easy product workup.
The trans-stereochemistry of epoxides 1a–p was con-
firmed by the coupling constants of the protons a and b to
the carbonyl group. For example, for 1c the 1H NMR con-
tained peaks at d = 4.07 ppm [d, J = 2.0 Hz, 1 H, Ar-
CH(-O-)CH] and 4.21 ppm [d, J = 2.0 Hz, 1 H, C(O)CH],
in which the coupling constant (2 Hz) indicates a trans-
substituted epoxide. Similarly, the cis-configuration of 2-
hydroxyindan-1-ones 2a–p was confirmed by the cou-
pling constants of the protons at positions 2 and 3. For ex-
The catalytic efficiency of metal halides is given in
Table 1. Zirconium, aluminum, and bismuth salts (entries
2–4) showed poor to moderate catalytic activity in the for-
mation of 2a (Scheme 1). Other metal halides (e.g., with
10 mol% of ZnO, TaCl5, ZnCl2, CuBr2, SnCl2, LaCl3,
LiBr, TiCl4, FeCl3, or FeCl3·6 H2O) failed to give the
product even after reaction for a prolonged time. Indi-
um(III) chloride (entry 1) was found to be the most effi-
cient catalyst at 10 mol% catalyst loading, which gave the
optimal yield (95%). To optimize the catalyst loading, the
reactions were carried out with 2, 5, 10, and 20 mol% cat-
alyst (entries 1, 5–7) in dichloromethane and the efficien-
cy of the catalyst loading was determined from the time
needed for the complete conversion of the epoxide 1a. Us-
ing 2 and 5 mol% indium(III) chloride gave the product 2a
in lower yield and the reaction slowly, whereas using 20
mol% indium(III) chloride the product 2a was formed in
82% yield together with 2,5-dichloro-3-(4-chlorophenyl)-
2,3-dihydro-1H-inden-1-one (7%), which was isolated
and characterized by GCMS/HRMS, without improve-
ment in the yield or reaction time.
1
ample, for 2c the H NMR contained peaks at d = 5.18
ppm (d, J = 3.5 Hz, 1 H, H3) and 5.33 ppm (d, J = 3.5 Hz,
1 H, H2), in which the coupling constant (3.5 Hz) indi-
cates a cis-configuration. The stereoselectivity and high
yields for indan-1-ones under acidic condition might be
due to the carbon b to the carbonyl group possessing con-
siderable cationic character as it is also at the benzylic po-
sition and therefore resonance stabilized. The cis-
configuration in 3-aryl-2-hydroxyindan-1-ones 2a–p, fur-
Table 2 Indium(III) Chloride Catalyzed Intramolecular Friedel–
Crafts Alkylation Synthesis of 2-Hydroxyindan-1-ones
R2
R2
R1
R1
Table 1 Screening of Metal Salts and Optimization for Intramolec-
ular Friedel–Crafts Alkylation of Chalcone Epoxide 1a (Scheme 1)
1. InCl3 (10 mol%)
O
CH2Cl2, r.t., 4–5 h
OH
2. hydrolysis
Entry
Catalyst
InCl3
Loading (mol%) Time (h) Yielda (%)
O
O
1
2
3
4
5
6
7
10
10
10
10
2
4–5
20
90
<5
35
10
50
65
82b
1a–p
2a–p
ZrOCl2
anhyd AlCl3
BiCl3
Chalcone
epoxide
R1
R2
Product
Yielda
(%)
5
6
1a
1b
1c
1d
1e
1f
Cl
Cl
Cl
Cl
Cl
Cl
Br
Br
Br
Br
Br
Br
H
4-Cl
2a
2b
2c
2d
2e
2f
90
92
94
81
91
95
92
93
95
83
92
94
95
95
94
92
4-Me
4-Br
InCl3
16
15
InCl3
5
3,4,5-(MeO)3
3-O2N
H
InCl3
20
4–5
a Yields refer to isolated product 2a.
b Together with 2,5-dichloro-3-(4-chlorophenyl)- 2,3-dihydro-1H-
inden-1-one (7%).
1g
1h
1i
4-Me
4-Cl
2g
2h
2i
Various chalcones were prepared by the condensation of
acetophenones and aromatic aldehydes following a re-
ported procedure.26 Epoxidation of the chalcones was car-
ried out using sodium hydroxide and hydrogen peroxide
in aqueous tetrahydrofuran to give the corresponding ep-
oxides 1a–p in high yields (80–90%). Following a simple
experimental procedure, chalcone epoxides 1a–p were
dissolved in dichloromethane by stirring, indium(III)
chloride was added in one portion and the mixture was
stirred at room temperature for four to five hours. After
the usual workup, the 3-aryl-2-hydroxyindan-1-ones 2a–
p were obtained in 81–95% yields (Table 2).
4-Br
1j
3,4,5-(MeO)3
3-O2N
H
2j
1k
1l
2k
2l
1m
1n
1o
1p
H
2m
2n
2o
2p
H
4-Cl
H
3-O2N
4-Br
The assigned structures of chalcone epoxides 1a–p and
products 2a–p were confirmed on the basis of their spec-
H
a Yields refer to isolated products.
Synthesis 2011, No. 15, 2471–2477 © Thieme Stuttgart · New York

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Synthesis of 2-Hydroxyindan-1-one Derivatives
2473
4.21 [d, J = 2.0 Hz, 1 H, C(O)CH], 4.07 [d, J = 2.0 Hz, 1 H,
Ar-CH(-O-)CH].
R2
R2
13C NMR (125 MHz, CDCl3): d = 191.69 (C=O), 60.96 [C(O)-CH],
58.71 (Ar-CH-O), 140.76, 134.37, 133.62, 132.04, 129.82, 129.31,
127.40, 123.21.
InCl3 (10 mol%)
R1
R1
O
O
InCl3
R2
CH2Cl2, r.t., 4–5 h
R2
MS (EI, 70 eV): m/z (%) = 336 (21) [M+.], 139 (100).
O
O
O
1a–p
(4-Chlorophenyl)[3-(3, 4, 5-trimethoxyphenyl)oxiran-2-
yl]methanone (1d)
White crystalline solid; yield: 5638 mg (90%); mp 128–130 °C.
R1
R1
hydrolysis
O
IR (KBr): 2928 (arom C–H str), 1692 (C=O str), 1590 (arom C=C
str), 1462, 1399, 1233, 1130 (C–O–C str), 1007, 824 cm–1 (C–Cl
str).
OH
InCl3
O
(intermediates)
81–95%
1H NMR (500 MHz, CDCl3): d = 7.99 (d, J = 8.5 Hz, 2 H, HAr), 7.47
(d, J = 8.5 Hz, 2 H, HAr), 6.60 (s, 2 H, HAr), 4.20 [d, J = 1.5 Hz, 1 H,
C(O)CH], 4.04 [d, J = 1.5 Hz, 1 H, Ar-CH(-O-)CH], 3.89 (s, 9 H,
OMe).
2a–p
Scheme 2
13C NMR (125 MHz, CDCl3): d = 191.89 (C=O), 153.79, 140.65,
138.74, 133.72, 130.84, 129.83, 129.26, 102.57, 60.97 [C(O)-CH],
59.54 (Ar-CH-O), 56.22 (OMe).
ther support benzylic resonance stabilization, which re-
sults in an SN1-like mechanism. Hence, the epoxide ring
regioselectively opened via the carbon b to the carbonyl
group (Scheme 2).
MS (EI, 70 eV): m/z (%) = 348 (16) [M+.], 219 (53), 181 (100).
In conclusion, we have explored the properties of differ-
ent metal halides for as mild and efficient catalysts for
chalcone epoxide ring opening and intramolecular
Friedel–Crafts alkylation in the regioselective synthesis
of 3-aryl-2-hydroxyindan-1-ones. To the best of our
knowledge, indium(III) chloride has not been studied in
this capacity before and therefore represents a novel sub-
ject for investigation.
(4-Chlorophenyl)[3-(3-nitrophenyl)oxiran-2-yl]methanone (1e)
White crystalline solid; yield: 4745 mg (87%); mp 126–128 °C.
IR (KBr): 3091, 2971 (arom C–H str), 1687 (C=O str), 1582 (arom
C=C str), 1523 (N–O, str), 1353 (N–O bending), 1237, 1003, 732
cm–1 (C–Cl str).
1H NMR (500 MHz, CDCl3): d = 8.27 (d, J = 8.5 Hz, 2 H, HAr), 8.01
(dd, J = 7.0, 1.5 Hz, 2 H, HAr), 7.74 (d, J = 7.5 Hz, 1 H, HAr), 7.63
(m, 1 H, HAr), 7.52 (m, 2 H, HAr), 4.27 [d, J = 1.5 Hz, 1 H, C(O)CH],
4.24 [d, J = 1.5 Hz, 1 H, Ar-CH(-O-)CH].
13C NMR (125 MHz, CDCl3): d = 191.18 (C=O), 148.74, 141.02,
137.70, 133.49, 131.75, 129.98, 129.89, 129.40, 124.00, 120.80,
60.76 [C(O)-CH], 57.96 (Ar-CH-O).
Organic solvents were dried by standard methods when necessary.
Commercially available reagents were used without further purifi-
cation unless mentioned. All reactions were monitored by TLC us-
ing precoated silica gel aluminum plates. Visualization of TLC
plates was accomplished with UV lamp or in an I2 chamber. Column
chromatography was performed using silica gel 100–200 mesh size
(SD Fine-Chem Limited) with EtOAc–hexanes as eluent; petro-
leum ether = PE. Melting points were recorded on perfit apparatus
and are uncorrected. 1H and 13C NMR spectra were recorded at 500
MS (EI, 70 eV): m/z (%) = 303 (34) [M+.], 139 (100).
(4-Bromophenyl)[3-(4-bromophenyl)oxiran-2-yl]methanone
(1i)
White crystalline solid; yield: 5883 mg (86%); mp 124–126 °C.
1
IR (KBr): 3091, 2924 (arom C–H str), 1674 (C=O str), 1579 (arom
C=C str), 1398, 1234, 1006, 880, 812 cm–1 (C–Br str).
1H NMR (500 MHz, CDCl3): d = 7.90 (d, J = 8.5 Hz, 2 H, HAr), 7.67
(d, J = 8.0 Hz, 2 H, HAr), 7.56 (d, J = 7.0 Hz, 2 H, HAr), 7.27 (m, 2
H, HAr), 4.19 [d, J = 1.5 Hz, 1 H, C(O)CH], 4.07 [d, J = 1.5 Hz, 1
H, Ar-CH(-O-)CH].
13C NMR (125 MHz, CDCl3): d = 191.91 (C=O), 134.36, 134.01,
132.31, 132.04, 129.87, 129.54, 127.40, 123.22, 60.94 [C(O)-CH],
58.72 (Ar-CH-O).
and 125 MHz, respectively; H NMR spectra were recorded in
CDCl3 using TMS as an internal standard. Mass spectra were re-
corded by GC-MS and EI-MS.
Chalcone Epoxides 1; General Procedure
A 5 M aq NaOH soln (10 mL) was added dropwise to a stirred soln
of chalcone (18 mmol) in H2O–THF (1:2, 30 mL) and further stirred
for 10 min. Then, H2O2 (15 mL, 30 wt%) was added dropwise and
the mixture was stirred at r.t. for 6–7 h (TLC monitoring). The mix-
ture was poured into H2O and the resulting precipitate was filtered,
washed with H2O, and dried under reduced pressure. The product
was recrystallized (EtOH) or subjected to column chromatography
(silica gel, PE–CH2Cl2, 8:2). Spectral data are given below for new
compounds. Epoxides 1a,b,f–h,l–n,p are known.27
MS (EI, 70 eV): m/z (%) = 380 (16) [M+.], 183 (83), 89 (100).
(4-Bromophenyl)[3-(3,4,5-trimethoxyphenyl)oxiran-2-yl]meth-
anone (1j)
White crystalline solid; yield: 5998 mg (85%); mp 130–132 °C.
[3-(4-Bromophenyl)oxiran-2-yl](4-chlorophenyl)methanone
(1c)
White solid; yield: 5383 mg (89%); mp 127–129 °C.
IR (KBr): 2940 (arom C–H str), 1692 (C=O str), 1590 (arom C=C
str), 1232, 1129 (C–O–C str), 1005, 826, 735, 686 cm–1 (C–Br str).
1H NMR (500 MHz, CDCl3): d = 7.92 (d, J = 9.0 Hz, 2 H, HAr), 7.68
(d, J = 9.0 Hz, 2 H, HAr) 6.60 (s, 2 H, HAr), 4.20 [d, J = 1.5 Hz, 1 H,
C(O)CH], 4.05 [d, J = 1.5 Hz, 1 H, Ar-CH(-O-)CH], 3.90 (s, 9 H,
OMe).
IR (KBr): 3039 (arom C–H str), 1675 (C=O str), 1587 (arom C=C
str), 1430, 1400, 1236, 1177, 1092, 1011, 735 cm–1 (C–Cl str).
1H NMR (500 MHz, CDCl3): d = 7.99 (dd, J = 7.0, 2.0 Hz, 2 H,
HAr), 7.54 (m, 4 H, HAr), 7.27 (dd, J = 7.0, 2.0 Hz, 2 H, HAr),
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N. Ahmed et al.
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13C NMR (125 MHz, CDCl3): d = 192.11 (C=O), 153.79, 138.75,
134.11, 130.82, 129.88, 129.42, 102.57, 60.97 [C(O)-CH], 59.55
(Ar-CH-O), 56.23 (OMe).
IR (KBr): 3439 (OH str), 2922 (arom C–H str), 1670 (C=O str),
1594 (arom C=C str), 1491, 1399, 1296, 1095, 760 cm–1 (C–Cl str).
1H NMR (500 MHz, CDCl3): d = 8.01 (dd, J = 8.0, 2.0 Hz, 2 H,
HAr), 7.74 (m, 1 H, HAr), 7.54 (m, 2 H, HAr), 7.21 (m, 2 H, HAr), 5.02
(d, J = 4.0 Hz, 1 H, H2), 4.95 (d, J = 4.0 Hz, 1 H, H3), 3.68 (br s, 1
H, D2O exchangeable), 2.49 (s, 3 H, CH3).
MS (EI, 70 eV): m/z (%) = 392 (15) [M+.], 181 (92), 105 (100).
(4-Bromophenyl)[3-(3-nitrophenyl)oxiran-2-yl]methanone(1k)
White crystalline solid; yield: 5309 mg (85%); mp 132–134 °C.
13C NMR (125 MHz, CDCl3): d = 193.48 (C=O), 63.91 (C2), 31.95
(C3), 146.50, 141.51, 131.46, 131.24, 130.38, 130.09, 129.83,
129.42, 128.89, 22.30.
MS (EI, 70 eV): m/z (%) = 272 (25) [M+.], 160 (55), 141 (72), 139
(100), 111 (62), 105 (73).
IR (KBr): 3087, 3041 (arom C–H str), 1687 (C=O str), 1581 (arom
C=C str), 1522 (N–O str), 1353 (N–O bending), 1236, 1072, 675
cm–1 (C–Br str).
1H NMR (500 MHz, CDCl3): d = 8.26 (dd, J = 4.0, 1.0 Hz, 2 H, HAr),
7.92 (dd, J = 9.0, 2.0 Hz, 2 H, HAr), 7.70 (m, 4 H, HAr) 4.26 [d, J =
2.0 Hz, 1 H, C(O)CH], 4.24 [d, J = 2.0 Hz, 1 H, Ar-CH(-O-)CH].
13C NMR (125 MHz, CDCl3): d = 191.41 (C=O), 137.66, 133.85,
132.41, 131.78, 130.01, 129.93, 129.83, 124.04, 120.81, 60.73
[C(O)-CH], 58.00 (Ar-CH-O).
3-(4-Bromophenyl)-5-chloro-2-hydroxy-2,3-dihydro-1H-inden-
1-one (2c)
Light yellow solid; yield: 790 mg (94%); mp 210–212 °C.
IR (KBr): 3426 (OH str), 2923 (arom C–H str), 1678 (C=O str),
1591 (arom C=C str), 1417, 1395, 1282, 1170, 1092, 757 cm–1 (C–
Cl str).
MS (EI, 70 eV): m/z (%) = 347 (19) [M+.], 185 (82), 183 (100).
[3-(3¢-Nitrophenyl)oxiran-2-yl](phenyl)methanone (1o)
1H NMR (500 MHz, CDCl3): d = 7.94 (d, J = 8.5 Hz, 1 H, HAr), 7.88
(m, 2 H, HAr), 7.47 (m, 3 H, HAr), 6.99 (d, J = 8.5 Hz, 1 H, HAr), 5.33
(d, J = 3.5 Hz, 1 H, H2), 5.18 (d, J = 3.5 Hz, 1 H, H3), 4.09 (br s, 1
H, D2O exchangeable).
13C NMR (125 MHz, CDCl3): d = 192.38 (C=O), 60.52 (C2), 31.86
(C3), 134.13, 134.08, 132.57, 132.41, 131.96, 131.57, 131.23,
130.81, 129.18, 128.70.
Yellow solid; yield: 4164 mg (86%); mp 125–129 °C.
IR (KBr): 1689 (C=O str), 1589 (arom C=C str), 1525 (N–O str),
1405, 1344 (N–O bending), 1232, 1081, 1009, 891, 812, 691, 601
cm–1.
1H NMR (500 MHz, CDCl3): d = 8.25–8.24 (m, 2 H, HAr), 8.03–
8.01 (m, 2 H, HAr), 7.73 (d, J = 6.5 Hz, 1 H, HAr), 7.67–7.59 (m, 2
H, HAr), 7.53–7.50 (dd, J = 8.0, 1.5 Hz, 2 H, HAr), 4.31 (d, J = 2.0
Hz, 1 H, C(O)CH], 4.22 (d, J = 1.5 Hz, 1 H, Ar-CH(-O-)CH].
MS (EI, 70 eV): m/z (%) = 336 (18) [M+.], 139 (100), 111 (53).
5-Chloro-2-hydroxy-3-(3,4,5-trimethoxyphenyl)-2,3-dihydro-
1H-inden-1-one (2d)
Light yellow solid; yield: 705 mg (81%); mp 220–222 °C.
13C NMR (125 MHz, CDCl3): d = 192.22 (C=O), 148.63, 137.91,
135.22, 134.69, 133.42, 131.89, 129.97, 129.44, 128.71, 128.42,
123.90, 120.79, 60.91 [C(O)-CH], 58.77 (Ar-CH-O).
IR (KBr): 3440 (OH str), 2920 (arom C–H str), 1666 (C=O str),
1592 (arom C=C str), 1406, 1336, 1233, 1125 (C–O–C str), 1091,
771 cm–1 (C–Cl str).
MS (EI, 70 eV): m/z (%) = 269 (24) [M+.], 253 (23), 105 (100), 91
(68).
3-Aryl-2-hydroxy-2,3-dihydro-1H-inden-1-ones 2a–p; General
Procedure
1H NMR (500 MHz, CDCl3): d = 7.63 (d, J = 8.0 Hz, 1 H, HAr), 7.57
(d, J = 8.0 Hz, 1 H, HAr), 7.39 (m, 1 H, HAr), 6.25 (s, 1 H, HAr), 6.19
(s, 1 H, HAr), 5.03 (d, J = 4.0 Hz, 1 H, H2), 4.92 (d, J = 4.0 Hz, 1 H,
H3), 4.49 (br s, 1 H, D2O exchangeable), 3.61 (s, 9 H, OMe).
13C NMR (125 MHz, CDCl3): d = 192.89 (C=O), 61.10 (C2), 30.96
(C3), 153.67, 134.06, 132.51, 131.73, 131.31, 129.91, 129.46,
128.95, 128.56, 107.26, 56.38 (OMe).
Chalcone epoxide 1 (2.5 mmol) was dissolved in CH2Cl2 (15 mL)
with stirring, InCl3 (0.25 mmol, 10 mol%) was added in one portion
and the mixture was stirred at r.t. for 4–5 h. H2O was added and the
mixture was extracted with CH2Cl2. The organic layer was dried
(anhyd Na2SO4), filtered, and evaporated under reduced pressure to
obtain the pure product or purified by flash column chromatography
(silica gel, hexane–CH2Cl2, 8:2) to afford the products in 81–95%
yields.
MS (EI, 70 eV): m/z (%) = 348 (29) [M+.], 181 (69), 139 (100), 111
(59).
5-Chloro-2-hydroxy-3-(3-nitrophenyl)-2,3-dihydro-1H-inden-
1-one (2e)
Light yellow solid; yield: 690 mg (91%); mp 215–217 °C.
5-Chloro-3-(4-chlorophenyl)-2-hydroxy-2,3-dihydro-1H-inden-
1-one (2a)
Light yellow solid; yield: 657 mg (90%); mp 202–204 °C.
IR (KBr): 3358 (OH str), 3075, 2924 (arom C–H str), 1686 (C=O
str), 1591 (arom C=C str), 1527 (N–O str), 1317 (N–O bending),
758 cm–1 (C–Cl str).
1H NMR (500 MHz, CDCl3): d = 8.17 (d, J = 1.5 Hz, 1 H, HAr), 8.04
(d, J = 8.5 Hz, 2 H, HAr), 7.55 (m, 2 H, HAr), 7.46 (d, J = 8.5 Hz, 2
H, HAr), 5.50 (d, J = 4.0 Hz, 1 H, H2), 5.25 (d, J = 4.0 Hz, 1 H, H3),
4.49 (br s, 1 H, D2O exchangeable).
13C NMR (125 MHz, CDCl3): d = 192.57 (C=O), 98.81 (C2), 31.95
(C3), 132.53, 131.92, 131.69, 131.30, 130.79, 129.19, 123.22.
MS (EI, 70 eV): m/z (%) = 303 (15) [M+.], 219 (45), 139 (90), 69
(100).
IR (KBr): 3438 (OH str), 2922 (arom C–H str), 1674 (C=O str),
1591 (arom C=C str), 1396, 1282, 1173, 1091, 756 cm–1 (C–Cl str).
1H NMR (500 MHz, CDCl3): d = 8.06 (d, J = 8.5 Hz, 1 H, HAr), 7.89
(m, 1 H, HAr), 7.53 (d, J = 8.5 Hz, 1 H, HAr), 7.47 (d, J = 8.5 Hz, 1
H, HAr), 7.28 (m, 2 H, HAr), 7.16 (d, J = 8.5 Hz, 1 H), 5.48 (d, J = 3.5
Hz, 1 H, H2), 5.21 (d, J = 3.5 Hz, 1 H, H3), 3.72 (br s, 1 H, D2O ex-
changeable).
13C NMR (125 MHz, CDCl3): d = 196.48 (C=O), 62.22 (C2), 29.71
(C3), 141.85, 141.29, 135.02, 134.10, 132.54, 131.41, 130.12,
129.50, 128.70.
MS (EI, 70 eV): m/z (%) = 292 (10) [M+.], 245 (25), 139 (100).
5-Chloro-2-hydroxy-3-phenyl-2,3-dihydro-1H-inden-1-one (2f)
Light yellow solid; yield: 613 mg (95%); mp 180–182 °C.
5-Chloro-2-hydroxy-3-(4-tolyl)-2,3-dihydro-1H-inden-1-one
(2b)
Light yellow solid; yield: 626 mg (92%); mp 182–184 °C.
Synthesis 2011, No. 15, 2471–2477 © Thieme Stuttgart · New York