A novel and highly efficient protocol for the synthesis of chalcone based 1,2-diazepine and 1,2-oxazepine derivatives

Article abstract of DOI:10.3987/COM-12-12444

A novel and highly efficient protocol is described for the synthesis of chalcone based 1,2-diazepine and 1,2-oxazepine derivatives. Under neat condition, the mixing and grinding of 1,5-diketones and hydrazine gave the cyclocondensation products in quantitative yields within 10-20 min at room temperature. Similarly, novel chalcone based 1,2-oxazepines were synthesized in excellent yields (85-88%) in 2-3 h at refluxed by the condensation of 1,5-diktones and hydroxylamine hydrochloride in water-ethanolic base.

Full text of DOI:10.3987/COM-12-12444

HETEROCYCLES, Vol. 85, No. 5, 2012
1155
HETEROCYCLES, Vol. 85, No. 5, 2012, pp. 1155 - 1177. © 2012 The Japan Institute of Heterocyclic Chemistry
Received, 8th February, 2012, Accepted, 19th March, 2012, Published online, 23rd March, 2012
DOI: 10.3987/COM-12-12444
A NOVEL AND HIGHLY EFFICIENT PROTOCOL FOR THE
SYNTHESIS
OF
CHALCONE
BASED
1,2-DIAZEPINE
AND
1,2-OXAZEPINE DERIVATIVES
B. Venkata Babu and Naseem Ahmed*
Department of Chemistry, Indian Institute of Technology, Roorkee 247 667,
Uttarakhand, India. Fax: +91-1332-285745. E-mail address: nasemfcy@iitr.ernet.in
Abstract – A novel and highly efficient protocol is described for the synthesis of
chalcone based 1,2-diazepine and 1,2-oxazepine derivatives. Under neat condition,
the mixing and grinding of 1,5-diketones and hydrazine gave the
cyclocondensation products in quantitative yields within 10-20 min at room
temperature. Similarly, novel chalcone based 1,2-oxazepines were synthesized
in excellent yields (85-88%) in 2-3 h at refluxed by the condensation of
1,5-diktones and hydroxylamine hydrochloride in water-ethanolic base.
INTRODUCTION
Substituted seven-membered heterocyclics like diazepine1,2 and oxazepine3,4 derivatives have received
much attention in the recent years owing to their wide range of biological and pharmaceutical importance.
An appropriate substitution and functionalization of diazepines and oxazepines have improved potentially
their pharmacological properties. For example, some pyrrolo-based diazepines,2c oxazepines3c and their
derivatives3 have shown excellent biological activities (Figure 1).5 Many other 1,2-oxazepine derivatives
are known to be potential opioid analgesics3b and 1,2-diazepine derivatives are used as antihypertensive
drugs and act as potential ACE inhibitors.2b
Due to the growing awareness about environmental concerns, organic chemists are under increasing
pressure to alter current working practices for the greener and sustainable development in academia as well
as industry research to find environmentally benign alternatives and efficient synthetic methods. Recently,
there has been incredible interest in the synthetic manipulation of biologically active and functionalized
indanedione derivatives.6-8 Previous works have shown that fusing an indeno moiety to the core structure of
a natural products enhanced the pharmacologic potential of a target molecule. Based on this veracity, the

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HETEROCYCLES, Vol. 85, No. 5, 2012
different derivatives have been synthesized as potential drug candidates in a wide range of bioactivities
including antioxidants, anticoagulants, antibacterial, Cyclin-Dependent Kinases (CDK) inhibitors,
neuroprotective agent,9 and potential antitumor agents.7
We herein report a novel and highly efficient protocol in the synthesis of 1,2-diazepines and 1,2-oxazepines
using chalcone and indeno moieties in search of pharmacologically active molecules. 1,2-Diazepines
(4,5-dihydro indeno[1,2-c][1,2]diazepin-6(1H)-ones) synthesis is reported with 1,5-diketones and
hydrazine in iso-propyl alcohol and acetic acid. This reaction has suffered with the use of acid catalyst,
solvent, longer reaction time and high temperature.10
R1
NH
R2
NH-CO2CH2C6H5
O
OR
MeO
R1
O
O
N
O
N
N
N
CO2H
N
CO2H
Bn
R1 = H (or) CO2H
R2 = CO2H(or) H
O
pyrrolo-[1,2-b][1,2]diazepine
2,3,4,7-tetrahydro-[1,2]oxazepine
Me
Me
N
F
F
O
O
R
O
N
O
O
N
O
N
O
N
R
H
N
N
Me
O
O
H2N
H2N
GYKI 53655, R = NHMe (CAS 143692-18-6)
GYKI 53405, R = Me (CAS 143691-37-6)
GYKI 52466
(CAS 102771-26-6)
1,4-dioxo-benzo[d][1,2]diazepin derivatives
Figure 1. Bioactive diazepine and oxazepine molecules
RESULTS AND DISCUSSION
Reaction between 1,3-indanedione and chalcones
1,3-Indanedione11 and chalcones12 were prepared by following the literature procedures. Similarly,
1,5-diketones were obtained in excellent yields (80-95%) using 1,3-indanedione and chalcones with
modification of reported method13,14 in the presence of K2CO3 at 0 °C to room temperature in ethyl acetate.
This method has advantage over previously reported procedures in yields and mild reaction conditions. We
also tried other bases like NaOH, KOH, AcONa, NH3, Et3N, n-BuLi and Lewis acids like AcOH and ZnO,
but they failed to give the products. The assigned structure of novel 1,5-diketones 3a-3u was confirmed

HETEROCYCLES, Vol. 85, No. 5, 2012
1157
1
on the basis of their spectral analysis (IR, H and 13C-NMR, and ESI-MS) and others compared with
available reported data in the literature.13 For example, 2-[3-(4-chlorophenyl)-1-(3-nitrophenyl)-3-
oxopropyl]-2H-indene-1,3-dione 3b found 92.0% pure in hplc analysis, the IR spectral peaks at 1730, 1703
cm-1 showed the presence of saturated carbonyl groups. The 1H NMR spectrum contained peak at δ 3.37
ppm (d, J = 8.0 Hz, 1H), in which the coupling constant (J = 8.0 Hz) indicated the indandione ring proton at
2-position coupled with a trans proton. Peak at δ 4.41 ppm (m, 1H) indicated for Ar-CH-CH2-proton,
coupled with three adjacent protons. Similarly, peaks at δ 4.17 ppm (dd, J = 13.0 Hz, 7.0 Hz, 1H) and 3.52
ppm (dd, J = 13.0 Hz, 7.0 Hz, 1H) indicated the diastereotopic protons of Ar-CH-CHa-(CO)-Ar and
Ar-(CH)-CHb-(CO)-Ar, respectively. The 13C NMR spectrum gave peaks at δ 199.5, 198.5 and 196.5 ppm
for three characteristic carbonyl carbons, 56.71 ppm for indandione carbon, 40.66 ppm for Ar-CH-CH2-
carbon and 38.8 ppm for Ar-CH-CH2-CO-Ar carbon. ESI-MS also gave the molecular ion peak at 434
[M+H+] for compound 3b. Similarly, other derivatives 3a, 3c-3u were confirmed on their spectral analysis
(experimental section).
Reaction between 1,5-diketone and hydrazine
Initially, the reaction was carried out between 1,5-diketones and hydrazine in 1:1 and 1:2 molar ratios
respectively under neat condition. However, 1,5-diketones remained unconsumed and poor yields was
obtained even prolonging the reaction time at room temperature (Table 1, entries 1 & 2). Then, we carried
out the reaction using 1,5-diketone and hydrazine in 1:3 molar ratio in the presence of p-toluenesulfonic
acid (PTSA) catalyst in EtOH at room temperature. The product was obtained in good yields (75%) in 2.30
h (Table 1, entry 3). The reaction was serendipitously improved in yields (96%) by grinding under neat
condition for 10-20 min in the later molar ratio (Table 1, entry 4). The purity of the product was good
enough for spectral analysis. Based on the optimized molar ratio (1:3) under grinding and neat condition, all
products 4a-r was obtained in excellent yields (Table 2). In the case of 2’-aminochalcone based
1,5-diketones 3s-3u, the reaction with hydrazine in the optimized reaction condition gave the low yields
even prolonged reaction time (Table 2). This might be due to the stronger hydrogen bonding between
carbonyl oxygen and NH2 group, which stalled the water elimination and so the reaction became sluggish.
However, we got the products in moderate yields (30-40%) in heating condition at 80-85 oC. In the case of
2’-hydroxychalcone based 1,5-diketones 3o-3r, the reaction with hydrazine in the optimized reaction
condition gave good yield within 10-20 min (Table 2). This might be due to the poor hydrogen bonding
between carbonyl oxygen and OH group compared to amino group.

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HETEROCYCLES, Vol. 85, No. 5, 2012
Table 1. Optimization of cyclocondensation reaction in 3b
s.no 1,5-diketone:N2H4(mmol) rxn. time (min) yield (%)
1
2
3
4
1:1
1:2
1:3
1:3
20 - 50a
20 - 50a
120 -150b
10- 20a
35
60
75
96
a reaction in neat grinding. b reaction with PTSA stirred in EtOH at rt.
All new products were confirmed by their spectral analysis (IR, 1H- and 13C-NMR, and ESI-MS) and others
compared with reported data in the literature.10 For example, (2E,5aE)-3-(4-chlorophenyl)-5-
(3-nitrophenyl)-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one 4b, the IR spectral peaks at 3434, 1681
cm-1 observed due to NH and carbonyl groups respectively. The 1H NMR spectrum contained peak at δ 4.70
ppm (dd, J = 5.0 Hz, 2.0 Hz, 1H), in which the coupling constant (J = 5.0 Hz) indicated for Ar-CH-CH2-
cyclic proton of diazepine ring. Peaks at δ 3.42 ppm (dd, J = 13.5 Hz, 5.0 Hz, 1H) and 3.07 ppm (dd, J =
13.5 Hz, 3.0 Hz, 1H) indicated for Ar-CH-CHa- and Ar-CH-CHb-diazepine ring diastereotopic protons. The
13C NMR spectrum gave peaks at δ 191.15 ppm for the characteristic carbonyl carbon, 40.51 ppm for
Ar-CH-CH2, and 38.11 ppm for Ar-CH-CH2- of diazepine ring carbons. Further, ESI-MS showed the
molecular ion peak at 430.0962 [M+H+] for the compound 4b. Similarly, other derivatives 4a, 4c-4r were
confirmed on their spectral analysis (experimental section).
Reaction between 1,5-diketone and NH2OH·HCl
The reaction between 1,5-diketones and NH2OH.HCl in 1:1, 1:2 and 1:3 molar ratios gave poor or no
yield in the presence of base under grinding and/or neat condition even prolonging the reaction time at
room temperature or heating conditions. Then, we carried out this reaction in 1:2 molar ratio in water
ethanolic base at refluxed temperature, which gave 1,2-oxazepines in excellent yields (85-88%) within
1
13
2-3 h. These products were confirmed by their spectral analysis like IR, H- and C-NMR and ESI-MS.
For example, (2E,5aE)-3-(4-bromophenyl)-5-phenyl-4,5-dihydroindeno[2,1-f][1,2]oxazepin-6-one 5b,
the IR spectral peak at 1685 cm-1 indicated a carbonyl group. The 1H NMR spectrum peak at δ 5.68 ppm
(dd, J = 8.5 Hz, 2.5 Hz, 1H) showed Ar-CH-CH2- proton of oxazepine ring, in which the coupling
constant (J = 8.0 Hz and 2.5 Hz) indicated the presence of trans and cis protons. Peaks at δ 3.66 ppm (dd,
J = 12.5 Hz, 8.5 Hz, 1H) and 3.24 ppm (dd, J = 13.0 Hz, 8.0 Hz, 1H) indicated geminal and trans
coupling of Ar-CH-CHa- with Ar-CH-CHb- and Ar-CH-CH2-oxazepine ring diastereotopic protons
13
respectively. The C NMR spectrum gave peak at δ 193.10 ppm for the characteristic carbonyl carbon,

HETEROCYCLES, Vol. 85, No. 5, 2012
1159
42.85 ppm for Ar-CH-CH2, and 39.64 ppm for Ar-CH-CH2 of oxazepine ring carbons. Further, ESI-MS
showed the molecular ion peak at 430.0440 [M+H+] for the compound 5b. Similarly, 5a was confirmed
on their spectral analysis (experimental section).
Table 2. Synthesis of 1,5-diketone, 1,2-diazepine and 1,2-oxazepine derivatives
R4
R5
R3
O
R1
N
N
H
85 - 96%
4a - 4u
R2
N2H4/ grinding
10-20 min, rt
R2
O
O
O
O
+
R3
R4
R1
K2CO3/EtOAc
0 °C- rt, 4 - 5 h
R2
R1
O
1a
2a - 2u
R3
O
R5
R1 = H, OH, NH2
R2 = H, Cl, Br, NO2
R3 = H, NO2,OMe
R4 = H,OMe,Me, Cl, Br
R5 = H,OMe
R5
R4
80 - 95%
3a - 3u
NH2OH.HCl
NaOH/ EtOH
reflux, 2- 3 h
R4
R5
O
R3
R1
O
N
85 - 88%
5a - 5b
R2
Yield (%)
Yield (%)
Indanedione
Chalcone
1,5-Diketone
Diazepin/Oxazepin
Me
Me
Cl
O
O
O
O
90
93a
O
O
N
H
N
O
1a
Me
3a
Cl
Cl
2a
4a

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HETEROCYCLES, Vol. 85, No. 5, 2012
Cl
NO2
NO2
O
O
1a
O
92
95a
N
O
H
N
NO2
O
Cl
Cl
2b
3b
4b
Cl
O
O
1a
1a
O
91
95a
O
N
H
N
O
Cl
Cl
3c
4c
2c
Cl
Cl
Cl
O
O
89
94a
O
O
N
H
O
N
Cl
Cl
Cl
3d
4d
2d
Br
Me
Me
O
O
1a
1a
O
O
95
91a
N
O
H
N
Me
Br
Br
3e
2e
MeO
4e
Br
OMe
OMe
MeO
OMe
OMe
O
O
90a
O
O
87
N
N
H
OMe
OMe
O
Br
MeO
Br
2f
3f
4f
Br
O
O
O
1a
1a
O
N
92
92
93a
O
H
N
Br
Br
3g
4g
2g
Br
Cl
Cl
O
O
O
O
O
96a
N
H
N
Br
Br
Cl

HETEROCYCLES, Vol. 85, No. 5, 2012
1161
2h
2i
3h
4h
O
O
1a
1a
O
O
N
H
94
96a
N
O
3i
4i
4j
Me
Me
O
O
O
93
94a
O
O
N
H
N
Me
3j
2j
Cl
Cl
O
O
1a
O
90
95a
O
O
N
H
N
Cl
2k
2l
3k
4k
NO2
NO2
O
O
1a
1a
O
O
91
91a
N
H
N
NO2
NO2
O
3l
4l
O
N
O
O
89
92a
H
O
N
O
NO2
NO2
2m
3m
4m
Me
NO2
Me
O
N
O
1a
1a
O
O
H
N
88
87
92a
O
NO2
NO2
Me
4n
2n
3n
3o
Cl
Cl
O
O
O
OH
O
89 a
O
OH
OH
N
N
H
Cl
2o
4o

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HETEROCYCLES, Vol. 85, No. 5, 2012
NO2
NO2
O
N
O
OH
1a
OH
O
OH
O
85a
87a
89
NO2
N
H
O
4p
3p
2p
Me
Me
O
O
OH
O
1a
1a
88
OH
O
OH
O
N
N
H
Me
3q
2q
MeO
4q
MeO
O
OMe
OMe
OMe
OMe
O
OH
O
90a
O
OH
OH
89
OMe
OMe
O
N
N
H
MeO
2r
3r
4r
Cl
Cl
O
O
O
NH2
1a
1a
O
40b
O
NH2
NH2
85
N
N
H
Cl
3s
2s
2t
4s
Me
Me
O
O
O
NH2
O
O
NH2
NH2
83
80
36b
30b
N
N
H
Me
3t
4t
NO2
NH2
NO2
O
O
NH2
NO2
1a
1a
O
NH2
O
N
N
H
O
3u
2u
4u
Me
Me
Br
O
O
O
95
85c
O
O
O
N
Br
Br
Me
5a
2e
3e

HETEROCYCLES, Vol. 85, No. 5, 2012
1163
Br
O
O
88c
O
1a
92
O
O
N
O
Br
Br
5b
2g
3g
a reaction time 10-20 min neat grinding. b reaction time 10-20 min at 80 °C. c reaction time 2-3 h reflux.
In conclusion, we have reported a novel, highly efficient protocol for the synthesis of chalcone based
1,2-diazepines and 1,2-oxazepines. Under neat condition, grinding of 1,5-diketones and hydrazine gave
the cyclocondensation products (1,2-diazepines) in quantitative yields within 10-20 min at room
temperature. Similarly, novel chalcone based 1,2-oxazepines were obtained by the condensation of
1,5-diktones and hydroxylamine hydrochloride in excellent yields (85-88%) at refluxed in 2-3 h using
water-ethanolic base.
MECHANISM
HX
N
O
NH -NH
2
2
O
H
O
N
(or)
X
HO
NH OH.HCl
2
-H O
2
H
O
O
O
where X = NH (or) O
H
O
N
N
X
X
H
-H O
2
-H
H
O
O
EXPERIMENTAL
General Methods: Organic solvents were dried by standard methods when necessary. Commercially
available reagents were used without further purification unless mentioned. All reactions were monitored
by TLC using precoated silica gel aluminum plates. Visualization of TLC plates was accomplished with
UV lamp or in iodine chamber. The column chromatography was performed using silica gel 100–200
mesh size (SD Fine-Chem Limited) with ethyl acetate/hexanes as an eluent system. Melting points were
recorded on perfit apparatus and are uncorrected. IR spectra of the compounds were expressed as wave

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HETEROCYCLES, Vol. 85, No. 5, 2012
1
13
1
numbers (cm-1). H and C NMR spectra were recorded at 500 and 125 MHz, respectively. H NMR
spectra were recorded in CDCl3 using tetramethylsilane (TMS) as an internal standard. Chemical shifts of
1H NMR spectra were given in parts per million with respect to TMS, and the coupling constant J was
measured in Hz. Data are reported as follows: chemical shifts, multiplicity (s = singlet, d = doublet, t =
triplet, q = quartet, m = multiplet, dd = double doublet). Mass spectra were recorded by EI-MS and
HRMS. Purity of compounds 3a-3u was determined by HPLC (SHIMADZU LC-2010AHT, UV detector
(λmax 260 nm) using LICHROSPHER-100 (RP-C18) column.
General Procedure: (a) Synthesis of 1,5-diketones: A mixture of indanedione (1.1 mmol) and K2CO3 (1.2
mmol) was dissolved in EtOAc (4 mL) and cooled to 0 °C. Chalcone (1.0 mmol) dissolved in EtOAc (3
mL) was added dropwise in the above stirred mixture at 0 °C. Followed by, the reaction mixture was
slowly warmed at room temperature. TLC monitoring, the reaction mixture was poured into water (4-5 h)
and extracted with EtOAc (3 x 10 mL). The combined organic layer was dried over anhy. MgSO4 and the
solvent was evaporated under vacuum. The residue was recrystalized with suitable solvent (MeOH) to
afford excellent yields (upto 95%) as a solid.
2-(3-(4-Chlorophenyl)-3-oxo-1-p-tolylpropyl)-2H-indene-1,3-dione (3a): Yellow solid. Yield: 362.6
mg (90%). Mp 118-120 oC. IR νmax (KBr, cm-1): 3132, 3017 (aromatic C-H str), 1720, 1703 (C=O str), 1588
(aromatic, C=C str), 1400, 1254, 1198, 1087, 817, 766. 1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.26 (m, 1H),
4.17 (dd, J = 10.0 Hz, 4.0 Hz, 1H), 3.54 (m, 2H), 2.17 (s, 3H), 7.94 (d, J = 9.0 Hz, 2H), 7.86 (d, J = 7.0 Hz,
1H), 7.80 (d, J = 7.5 Hz, 1H), 7.72 (m, 2H) 7.43 (d, J = 8.0 Hz, 2H), 7.11 (d, J = 8.0 Hz, 2H), 6.93 (d, J =
8.0 Hz, 2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 200.0, 198.7, 196.8 (C=O), 141.9, 141.6, 139.0, 136.6,
136.0, 134.7, 134.7, 134.5, 128.9, 128.5, 128.2, 127.9, 127.5, 122.3, 122.1, 56.1, 40.3, 38.4, 20.2. MS
(ESI): m/z (%) 403 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C25H19ClO3: 403.1101; found 403.1092.
HPLC-purity 94.5%.
2-(3-(4-Chlorophenyl)-1-(3-nitrophenyl)-3-oxopropyl)-2H-indene-1,3-dione (3b): Yellow solid. Yield:
398 mg (92%). Mp 123-125 oC. IR νmax (KBr, cm-1): 3153, 2918, 1730, 1703 (C=O str), 1524 (aromatic,
C=C str), 1402, 1348, 1268, 1210, 1093, 828. 1H-NMR (500 MHz, CDCl3) δ (ppm): 4.41 (m, 1H), 4.17(dd,
J = 13.0 Hz, 7.0 Hz, 1H), 3.52 (dd, J = 12.5 Hz, 7.5 Hz, 1H), 3.37 (d, J = 8.0 Hz, 1H), 8.32 (d, J = 6.5 Hz,
1H), 8.07 (m, 1H), 7.90 (m, 2H), 7.84 (m, 2H), 7.79 (m, 1H), 7.73 (m, 1H), 7.68 (m, 1H), 7.54 (m, 2H), 7.43
13
(m, 1H). C-NMR (CDCl3, 125 MHz) δ (ppm): 199.5, 198.5, 196.5 (C=O), 148.2, 142.7, 142.3, 142.0,
140.1, 135.9, 135.1, 134.8, 129.6, 129.5, 129.2, 129.1, 123.2, 123.2, 122.4, 56.7, 40.7, 38.8. MS (ESI): m/z
(%): 434 [M+H+] C24H16ClNO5. HRMS-ESI (m/z): [M+H+] calcd for C24H16ClNO5: 434.0795; found
434.0780. HPLC-purity 92.0%.

HETEROCYCLES, Vol. 85, No. 5, 2012
1165
2-(3-(4-Chlorophenyl)-3-oxo-1-phenylpropyl)-2H-indene-1,3-dione (3c): Yellow solid. Yield: 354 mg
(91%). Mp 124-126 oC. IR νmax (KBr, cm-1): 3049, 2945, 1718, 1699 (C=O str), 1518 (aromatic, C=C str),
1
1430, 1355, 1249, 1225, 1075, 810. H-NMR (CDCl3, 500 MHz) δ (ppm): 4.31 (m, 1H), 4.13 (m, 1H),
3.61 (dd, J = 18.0 Hz, 5.0 Hz, 1H), 3.52 (d, J = 8.5 Hz, 1H) 7.92 (m, 2H), 7.80 (m, 2H), 7.72 (m, 2H),
7.63 (m, 1H), 7.43 (m, 2H), 7.19 (m, 2H), 7.12 (m, 2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 200.3,
199.1, 198.2 (C=O), 142.5, 138.9, 136.7, 135.6, 135.5, 133.3, 132.8, 129.8, 129.6, 129.2, 128.7, 128.6,
128.1, 123.1, 122.0, 56.8, 40.8, 38.8. MS (ESI): m/z (%) 389 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd
for C24H17ClO3: 389.0944; found 389.0928. HPLC-purity 91.8%.
2-(1,3-Bis(4-chlorophenyl)-3-oxopropyl)-2H-indene-1,3-dione (3d): Yellow solid. Yield: 376.5 mg
(89%). Mp 123-125 oC. IR νmax (KBr, cm-1): 3085, 3013 (aromatic C-H str), 1711, 1679 (C=O str), 1575
(aromatic, C=C str), 1421, 1345, 1211, 1087, 1005, 810, 765. 1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.29
(m, 1H), 4.12 (m, 1H), 3.72 (m, 1H), 3.58 (m, 1H), 7.83 (m, 2H), 7.74 (m, 2H), 7.40-7.38 (m, 4H), 7.18
13
(dd, J = 7.0 Hz, 1.5 Hz, 2H) 7.10 (dd, J = 7.0 Hz, 1.5 Hz, 2H). C-NMR (CDCl3, 125 MHz) δ (ppm):
200.4, 199.0, 197.0 (C=O), 143.8, 142.5, 139.9, 138.8, 136.7, 136.3, 135.7, 135.1, 133.0, 129.9, 129.7,
128.7, 128.4, 123.1, 123.0, 121.9, 56.7, 40.8, 38.8. MS (ESI) m/z (%) 423 [M+H+]. HRMS-ESI (m/z):
[M+H+] calcd for C24H16Cl2O3: 423.0555; found 423.0548. HPLC-purity 94.2%.
2-(3-(4-Bromophenyl)-3-oxo-1-p-tolylpropyl)-2H-indene-1,3-dione (3e): Yellow solid. Yield: 424.6
o
mg (95%). Mp 120-122 C. IR νmax (KBr, cm-1): 3135, 2914 (aromatic C-H str), 1739, 1705 (C=O str),
1672, 1590 (aromatic, C=C str), 1400, 1255, 1200, 1072, 813. 1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.26
(m, 1H), 4.15(dd, J = 11.0 Hz, 5.0 Hz, 1H), 3.52 (m, 2H), 2.17 (s, 3H), 7.81 (m, 3H), 7.79 (m, 1H), 7.72
(m, 2H), 7.60 (m, 2H), 7.11 (d, J = 8.0 Hz, 2H), 6.93 (d, J = 7.0 Hz, 2H). 13C-NMR (CDCl3, 125 MHz) δ
(ppm): 200.7, 199.4, 197.7 (C=O), 145.6, 142.6, 142.3, 137.3, 136.7, 135.7, 135.4, 131.9, 130.0, 129.8,
129.2, 128.6, 128.2, 123.0, 122.9, 120.5, 56.9, 41.7, 39.2, 20.9. MS (ESI): m/z (%) 447 [M+H+].
HRMS-ESI (m/z): [M+H+] calcd for C24H19BrO3: 447.0596; found 447.0580. HPLC-purity 94.0%.
2-(3-(4-Bromophenyl)-3-oxo-1-(3,4,5-trimethoxy phenyl)propyl)-2H-indene-1,3-dione (3f): Yellow
o
solid. Yield: 455 mg (87%). Mp 132-134 C. IR νmax (KBr, cm-1): 3104, 2930 (aromatic C-H str), 1725,
1
1701 (C=O str), 1587 (aromatic, C=C str), 1505, 1456, 1405, 1253, 1122, 1090, 821,763. H-NMR
(CDCl3, 500MHz) δ (ppm): 4.22 (m, 1H), 4.10 (m, 1H), 3.54 (m, 2H), 3.74 (s, 6H), 3.69 (s, 3H), 7.84 (m,
13
4H), 7.75 (m, 2H), 7.61 (d, J = 8.5 Hz, 2H), 6.44 (s, 2H). C-NMR (CDCl3, 125MHz) δ (ppm): 200.8,
199.4, 197.5 (C=O), 152.9, 142.7, 142.4, 136.8, 136.1, 135.6, 135.5, 132.0, 129.7, 129.1, 128.9, 128.5,
123.1, 122.1, 105.4, 60.7, 56.9, 56.1, 41.0, 40.2. MS (ESI): m/z (%) 523 [M+H+]. HRMS-ESI (m/z):
[M+H+] calcd for C27H23BrO6: 523.0756; found 523.0750. HPLC-purity 93.7%.

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2-(3-(4-Bromophenyl)-3-oxo-1-phenylpropyl)-2H-indene-1,3-dione (3g): Yellow solid. Yield: 398 mg
(92%). Mp 121-123 oC. IR νmax (KBr, cm-1): 3110, 3015, 2987 (aromatic C-H str), 1731, 1701 (C=O str),
1545 (aromatic, C=C str), 1468, 1387, 1221, 1097, 1045, 812. 1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.29
(m, 1H), 4.15 (m, 1H), 3.54 (m, 2H), 7.89 (dd, J = 6.0 Hz, 1.5 Hz, 2H), 7. 71 (m, 2H), 7.68 (m, 2H), 7.58
13
(m, 2H), 7.21 (m, 2H), 7.07 (m, 3H). C-NMR (CDCl3, 125MHz) δ (ppm): 200.6, 199.3, 197.6 (C=O),
142.6, 142.3, 140.3, 135.6, 135.4, 131.9, 129.9, 129.4, 128.7, 128.5, 127.4, 127.2, 126.9, 123.0, 122.9,
56.8, 40.9, 39.6. MS (ESI): m/z (%) 433 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C24H17BrO3:
433.0439; found 433.0422. HPLC-purity 92.3%.
2-(3-(4-Bromophenyl)-1-(4-chlorophenyl)-3-oxopropyl)-2H-indene-1,3-dione (3h): Yellow solid.
o
Yield: 429 mg (92%). Mp 120-122 C. IR νmax (KBr, cm-1): 3045, 2987 (aromatic C-H str), 1710, 1697
1
(C=O str), 1545 (aromatic, C=C str), 1420, 1329, 1189, 1121, 1023, 791. H-NMR (CDCl3, 500 MHz) δ
(ppm): 4.17 (m, 1H), 4.02 (dd, J = 18.0 Hz, 3.0 Hz, 1H), 3.49 (dd, J = 17.0 Hz, 4.0 Hz, 1H), 3.43 (d, J =
7.5 Hz, 1H), 7.84 (m, 2H), 7.77 (d, J = 6.5 Hz, 1H), 7.71 (d, J = 7.0 Hz, 1H), 7.62 (m, 2H), 7.43 (d, J =
8.0 Hz, 1H), 7.37 (m, 2H), 7.32 (d, J = 8.0 Hz, 1H), 7.14 (d, J = 8.0 Hz 1H), 7.03 (d, J = 8.0 Hz, 1H).
13C-NMR (CDCl3, 125 MHz) δ (ppm): 200.3, 200.0, 197.0 (C=O), 143.9, 142.4, 142.2, 139.8, 139.4,
135.7, 135.0, 132.3, 131.3, 130.2, 129.9, 129.5, 129.0, 123.1, 123.0, 121.1, 56.7, 40.7, 38.8. MS (ESI):
m/z (%) 467 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C24H16BrClO3: 467.0050; found 467.0032.
HPLC-purity 96.0%.
2-(3-Oxo-1,3-diphenylpropyl)-2H-indene-1,3-dione (3i): Yellow solid. Yield: 333.6 mg (94%). Mp
129-131 oC. IR νmax (KBr, cm-1): 3118, 3010, 2935 (aromatic C-H str), 1742, 1703 (C=O str), 1572, 1513
1
(aromatic, C=C str), 1425, 1379, 1156, 1035, 756. H-NMR (CDCl3, 500 MHz) δ (ppm): 4.18 (m, 1H),
4.06 (m, 1H) 3.43 (m, 2H), 7.56 (m, 2H), 7.48 (m, 2H), 7.38 (m, 2H), 7.33 (m, 2H), 7.29 (m, 1H), 7.18
(m, 1H), 7.15 (m, 2H), 6.96 (m, 2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 200.6, 199.4, 198.5, (C=O),
144.8, 142.6, 140.6, 138.2, 136.9, 135.2, 133.1, 132.9, 131.0, 130.6, 129.3, 128.7, 128.5, 122.9, 122.0,
56.9, 40.9, 39.6. MS (ESI): m/z (%) 355 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C24H18O3:
355.1334; found 355.1320. HPLC-purity 91.8%.
2-(3-Oxo-3-phenyl-1-p-tolylpropyl)-2H-indene-1,3-dione (3j): Yellow solid. Yield: 343.17 mg (93%).
Mp 125-127 °C. IR νmax (KBr, cm-1): 3102, 2997 (aromatic C-H str), 1735, 1699 (C=O str), 1536
1
(aromatic, C=C str), 1478, 1389, 1252, 1121, 1066, 813. H-NMR (CDCl3, 500 MHz) δ (ppm): 4.16 (m,
1H), 4.07 (dd, J = 13.5 Hz, 5.0 Hz, 1H), 3.45 (m, 2H), 2.03 (s, 3H), 7.86 (d, J = 7.0 Hz, 2H), 7.70 (d, J =
7.0 Hz, 1H), 7.64 (d, J = 7.0 Hz, 1H), 7.50 (m, 2H), 7.40 (m, 2H), 7.10 (m, 3H), 6.80 (m, 2H). 13C-NMR
(CDCl3, 125 MHz) δ (ppm): 200.7, 199.5, 198.7 (C=O), 144.9, 142.6, 142.3, 141.1, 138.3, 137.5, 136.9,

HETEROCYCLES, Vol. 85, No. 5, 2012
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135.4, 133.2, 132.7, 131.0, 129.8, 129.1, 129.0, 123.0, 121.1, 57.0, 41.1, 39.3, 20.7. MS (ESI): m/z (%)
369 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C25H20O3: 369.1491; found 369.1495. HPLC-purity
93.0%.
2-(1-(4-Chlorophenyl)-3-oxo-3-phenylpropyl)-2H-indene-1,3-dione (3k): Yellow solid. Yield: 350 mg
(90%). Mp 126-128 oC. IR νmax (KBr, cm-1): 3053, 2948, 1722, 1698 (C=O str), 1514 (aromatic, C=C str),
1
1432, 1352, 1251, 1221, 1073, 808. H-NMR (CDCl3, 500 MHz) δ (ppm): 4.30 (m, 1H), 4.15 (m, 1H),
3.63 (dd, J = 13.0 Hz, 5.0 Hz, 1H), 3.54 (d, J = 6.0 Hz, 1H), 7.90 (m, 2H), 7.84 (m, 2H), 7.75 (m, 2H),
13
7.61 (m, 1H), 7.46 (m, 2H), 7.20 (m, 2H), 7.10 (m, 2H). C-NMR (CDCl3, 125 MHz) δ (ppm): 200.4,
199.1, 198.2 (C=O), 142.5, 139.0,136.8, 135.6, 135.6, 133.4, 132.9, 129.9, 129.6, 129.3, 128.7, 128.6,
128.1, 123.1, 122.0, 56.9, 40.8, 38.8. MS (ESI): m/z (%) 389 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd
for C24H17ClO3: 389.0944; found 389.0950. HPLC-purity 92.4%.
2-(1-(3-Nitrophenyl)-3-oxo-3-phenylpropyl)-2H-indene-1,3-dione (3l): Yellow solid. Yield: 363 mg
(91%). Mp 134-136 oC. IR νmax (KBr, cm-1): 3095, 3043 (aromatic C-H str), 1705, 1675 (C=O str), 1587
(aromatic, C=C str), 1485, 1399, 1235, 1177, 1090, 817 (C-Cl, str). 1H-NMR (CDCl3, 500 MHz) δ (ppm):
4.37 (m, 1H), 4.05 (m, 1H) 3.64 (dd, J = 13.5 Hz, 6.0 Hz, 1H), 3.50 (m, 1H), 8.10 (d, J = 7.0 Hz, 1H),
7.90-7.85 (m, 3H), 7.76 (d, J = 7.5 Hz, 1H), 7.68 (m, 2H), 7.58 (d, J = 7.5 Hz, 1H), 7.49 (t, J = 7.0 Hz,
1H), 7.38 (m, 2H), 7.20 (m, 2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 199.5, 198.6, 197.7 (C=O),
148.2, 142.9, 142.3, 142.0, 136.5, 135.8, 135.1, 133.6, 129.5, 128.8, 128.6, 128.3, 128.1, 124.7, 123.3,
123.2, 122.3, 56.8, 40.7, 38.9. MS (ESI): m/z (%) 400 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for
C24H17NO5: 400.1185; found 400.1173. HPLC-purity 93.2%.
2-(3-(4-Nitrophenyl)-3-oxo-1-phenylpropyl)-2H-indene-1,3-dione (3m): Yellow solid. Yield: 355 mg
(89%). Mp 120-122 °C. IR νmax (KBr, cm-1): 3067, 2982 (aromatic C-H str), 1735, 1710 (C=O str), 1563
1
(aromatic, C=C str), 1425, 1352, 1232, 1141, 1096, 824. H-NMR (CDCl3, 500 MHz) δ (ppm): 4.20 (m,
2H), 3.55 (dd, J = 11.0 Hz, 3.0 Hz, 1H), 3.45 (d, J = 6.0 Hz, 1H), 8.17 (d, J = 8.0 Hz, 2H), 8.01 (m, 2H),
7.76 (d, J = 7.5 Hz, 1H), 7.68 (d, J = 7.0 Hz, 1H), 7.61 (m, 2H), 7.18 (m, 2H), 7.11 (m, 2H), 6.95 (m, 1H).
13C-NMR (CDCl3, 125 MHz) δ (ppm): 200.6, 199.2, 197.2 (C=O), 150.4, 142.5, 142.3, 141.3, 139.9,
135.6, 135.6, 129.2, 128.6, 128.3, 127.3, 123.9, 123.0, 122.9, 56.6, 41.6, 39.5.MS (ESI): m/z (%) 400
[M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C24H17NO5: 400.1185; found 400.1171. HPLC-purity
92.0%.
2-(3-(4-Nitrophenyl)-3-oxo-1-p-tolylpropyl)-2H-indene-1,3-dione (3n): Yellow solid. Yield: 363 mg
(88%). Mp 127-129 oC. IR νmax (KBr, cm-1): 3075, 2998 (aromatic C-H str), 1710, 1698 (C=O str), 1557

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1
(aromatic, C=C str), 1458, 1359, 1204, 1154, 1040, 799. H-NMR (CDCl3, 500 MHz) δ (ppm): 4.27 (m,
2H), 3.62 (m, 1H), 3.53 (m, 1H), 2.13 (s, 3H), 8.28 (m, 2H), 8.13 (m, 2H), 7.85 (d, J = 7.0 Hz, 1H), 7.79
(d, J = 6.0 Hz, 1H), 7.71 (m, 2H), 7.22 (d, J = 7.5 Hz, 2H), 6.91 (d, J = 8.0 Hz, 2H). 13C-NMR (CDCl3,
125 MHz) δ (ppm): 200.7, 199.2, 197.3 (C=O), 150.3, 142.6, 142.3, 141.3, 136.9, 135.5, 131.6, 129.9,
129.4, 128.8, 123.9, 123.0, 122.9, 120.3, 56.6, 40.7, 39.1, 20.9. MS (ESI): m/z (%) 414 [M+H+].
HRMS-ESI (m/z): [M+H+] calcd for C25H19NO5: 414.1341; found 414.1349. HPLC-purity 90.1%.
2-(1-(4-Chlorophenyl)-3-(2-hydroxyphenyl)-3-oxopropyl)-2H-indene-1,3-dione (3o): Yellow solid.
Yield: 351.5 mg (87%). Mp 116-118 °C. IR νmax (KBr, cm-1): 3434 (-OH str), 3110, 2912 (aromatic C-H
1
str), 1722, 1710 (C=O str), 1638 (aromatic, C=C str), 1480, 1443, 1253, 1154, 981, 853, 758. H-NMR
(CDCl3, 500 MHz) δ (ppm): 4.28 (m, 1H), 4.20 (dd, J = 17.5 Hz, 9.5 Hz, 1H), 3.76 (dd, J = 17.5 Hz, 5.0
Hz, 1H), 3.50 (d, J = 7.0 Hz, 1H), 12.07 (s, br, D2O exchangeble, 1H), 7.92 (dd, J = 8.0 Hz, 1.5 Hz, 1H),
7.86 (dd, J = 6.0 Hz, 1.5 Hz, 1H), 7.81 (m, 1H), 7.71 (m, 1H), 7.57 (m, 1H), 7.47 (m, 1H), 7.11 (d, J = 7.5
13
Hz, 2H), 6.93 (m, 4H). C-NMR (CDCl3, 125 MHz) δ (ppm): 201.0, 200.1, 198.9 (C=O), 162.4, 142.4,
142.1, 138.4, 136.6, 135.7, 135.6, 133.0, 129.9, 129.7, 128.6, 123.1, 122.9, 119.3, 119.1, 118.5, 56.8, 40.2,
38.5. MS (ESI): m/z (%) 405 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C24H17ClO4: 405.0984; found
405.0970. HPLC-purity 91.0%.
2-(3-(2-Hydroxyphenyl)-1-(3-nitrophenyl)-3-oxopropyl)-2H-indene-1,3-dione (3p): Yellow solid.
Yield: 369.2 mg (89%). Mp 182-184 °C. IR νmax (KBr, cm-1): 3420 (-OH str), 3115, 2952 (aromatic C-H
1
str), 1723, 1715 (C=O str), 1638 (aromatic, C=C str), 1485, 1405, 1248, 1179, 990, 820, 760. H-NMR
(CDCl3, 500 MHz) δ (ppm): 4.45 (m, 1H), 4.17 (dd, J = 18.0 Hz, 8.5 Hz, 1H), 3.76 (dd, J = 18.0 Hz, 6.5
Hz, 1H), 3.55 (d, J = 4.0 Hz, 1H), 11.89 (s, br, D2O exchangeble, 1H), 8.17 (d, J = 1.5 Hz, 1H), 7.98 (dd,
J = 8.5 Hz, 1.5 Hz, 1H), 7.90 (dd, J = 6.0 Hz, 2.0 Hz, 2H), 7.86 (m, 1H), 7.76 (m, 2H) 7.65 (d, J = 12.0
13
Hz, 1H), 7.47 (m, 1H), 7.36 (t, J = 8.0 Hz, 1H), 6.95 (m, 2H). C-NMR (CDCl3, 125 MHz) δ (ppm):
203.3, 199.3, 198.4 (C=O), 162.3, 148.1, 142.3, 142.2, 141.9, 136.8, 135.9, 134.9, 129.8, 129.5, 123.2,
122.4, 119.2, 118.6, 56.7, 40.1, 38.5. MS (ESI): m/z (%) 416 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd
for C24H17NO6: 416.1134; found 416.1123. HPLC-purity 91.3%.
2-(3-(2-Hydroxyphenyl)-3-oxo-1-p-tolylpropyl)-2H-indene-1,3-dione (3q): Yellow solid. Yield: 338
mg (88%). Mp 116-118 °C. IR νmax (KBr, cm-1): 3430 (-OH str), 3099, 2982 (aromatic C-H str), 1719,
1
1705 (C=O str), 1653 (aromatic, C=C str), 1452, 1325, 1215, 1131, 1026, 842. H-NMR (CDCl3, 500
MHz) δ (ppm): 4.28 (m, 1H), 4.20 (dd, J = 12.5 Hz, 7.5 Hz, 1H), 3.76 (dd, J = 12.0 Hz, 5.0 Hz, 1H), 3.50
(d, J = 4.0 Hz, 1H), 2.17 (s, 3H), 12.07 (s, br, D2O exchangeble, 1H), 7.92 (dd, J = 8.0 Hz, 1.5 Hz, 1H),
7.86 (d, J = 8.0 Hz,1H), 7.84 (d, J = 7.5 Hz, 1H), 7.72 (m, 1H), 7.56 (m, 1H), 7.48 (m, 1H), 7.11 (d, J =

HETEROCYCLES, Vol. 85, No. 5, 2012
1169
8.0 Hz, 2H), 6.94 (m, 4H). 13C-NMR (CDCl3, 125MHz) δ (ppm): 200.5, 200.4, 199.2 (C=O), 162.4,
142.6, 142.3, 136.9, 136.4, 135.4, 135.3, 130.0, 129.1, 128.1, 122.9, 122.8, 119.4, 119.0, 118.4, 56.9, 40.5,
39.0, 20.8. MS (ESI): m/z (%) 385 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C25H20O4: 385.1440;
found 385.1430. HPLC-purity 93.3%.
2-(3-(2-Hydroxyphenyl)-3-oxo-1-(3,4,5-trimethoxyphenyl)propyl)-2H-indene-1,3-dione (3r): Yellow
solid. Yield: 409.4 mg (89%). Mp 122-124 °C. IR νmax (KBr, cm-1): 3419 (-OH str), 3129, 2972 (aromatic
C-H str), 1730, 1703 (C=O str), 1630 (aromatic, C=C str), 1588, 1499, 1453, 1255, 1123, 999, 764.
1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.25 (m, 1H), 4.14 (dd, J = 13.5 Hz, 8.0 Hz, 1H), 4.00 (d, J = 8.5
Hz, 1H), 3.74 (s, 6H), 3.69 (s, 3H), 3.48 (d, J = 7.0 Hz, 1H), 12.07 (s, br, D2O exchangeble, 1H), 7.93 (dd,
J = 8.0 Hz, 2.0 Hz, 1H), 7.87 (m, 1H), 7.82 (m, 1H), 7.74 (m, 2H), 7.48 (t, 1H), 6.95 (m, 2H), 6.45 (s, 2H).
13C-NMR (CDCl3, 125 MHz) δ (ppm): 204.3, 200.6, 199.3 (C=O), 162.4, 152.9, 142.6, 142.3, 136.8,
136.6, 135.7, 135.5, 135.5, 129.9, 123.0, 122.7, 119.3, 119.0, 118.5, 60.6, 56.9, 56.0, 40.4, 39.9. MS
(ESI): m/z (%) 461 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C27H24O7: 461.1600; found 461.1583.
HPLC-purity 92.6%.
2-(3-(2-Aminophenyl)-1-(4-chlorophenyl)-3-oxopropyl)-2H-indene-1,3-dione (3s): Yellow solid.
Yield: 343.4 mg (85%). Mp 185-187 °C. IR νmax (KBr, cm-1): 3447 (-NH2 str), 3337, 3162 (aromatic C-H
str), 1735, 1705 (C=O str), 1618 (aromatic, C=C str), 1587, 1489, 1402, 1255, 1165, 1013, 743. 1H-NMR
(CDCl3, 500 MHz) δ (ppm): 4.29 (m, 1H), 4.11 (dd, J = 12.5 Hz, 7.0 Hz, 1H), 3.58 (dd, J = 12.5 Hz, 5.0
Hz, 1H), 3.51 (d, J = 6.5 Hz, 1H), 6.19 (s, br, D2O exchangeble, 2H), 7.86 (m, 3H), 7.73 (m, 2H), 7.26 (m,
13
1H), 7.21 (d, J = 8.5 Hz, 2H), 7.10 (dd, J = 7.0 Hz, 2.0 Hz, 2H), 6.68 (m, 1H), 6.65 (m, 1H). C-NMR
(CDCl3, 125 MHz) δ (ppm): 200.2, 199.9, 199.3 (C=O), 150.4, 142.5, 142.2, 139.1, 135.5, 134.5, 132.7,
131.0, 129.8, 128.5, 122.7, 122.8, 117.8, 117.3, 115.9, 57.0, 40.9, 39.1. MS (ESI): m/z (%) 404 [M+H+].
HRMS-ESI (m/z): [M+H+] calcd for C24H18ClNO3: 404.1053; found 404.1046. HPLC-purity 91.5%.
2-(3-(2-Aminophenyl)-3-oxo-1-p-tolylpropyl)-2H-indene-1,3-dione (3t): Yellow solid. Yield: 318 mg
(83%). Mp 120.122 °C. IR νmax (KBr, cm-1): 3446, 3336 (-NH2 str), 3152 (aromatic C-H str), 1726, 1705
1
(C=O str), 1613 (aromatic, C=C str), 1586, 1401, 1254, 1201, 1159, 1022, 749. H-NMR (CDCl3, 500
MHz) δ (ppm): 4.28 (m, 1H), 4.11 (dd, J = 13.0 Hz, 7.0 Hz, 1H), 3.55 (m, 2H), 2.18 (s, 3H), 6.21 (s, br,
D2O exchangeble, 2H), 7.87 (m, 3H), 7.70 (m, 2H), 7.25 (m, 2H), 7.14 (m, 1H), 6.94 (m, 2H), 6.66 (m,
2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 200.6, 200.5, 199.7, (C=O), 150.4, 142.7, 142.3, 137.6, 136.4,
135.2, 134.3, 131.1, 129.0, 128.2, 122.9, 122.7, 117.9, 117.3, 115.8, 57.2, 41.1, 39.4, 20.8. MS (ESI): m/z
(%): 384 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C25H21NO3: 384.1600; found 384.1588.
HPLC-purity 90.0%.

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2-(3-(2-Aminophenyl)-1-(3-nitrophenyl)-3-oxopropyl)-2H-indene-1,3-dione (3u): Yellow solid. Yield:
306 mg (80%). Mp 152-154 °C. IR νmax (KBr, cm-1): 3421, 3298 (-NH2 str), 3059 (aromatic C-H str),
1
1733, 1713 (C=O str), 1613 (aromatic, C=C str), 1543, 1415, 1322, 1202, 1121, 998, 742. H-NMR
(CDCl3, 500 MHz) δ (ppm): 4.36 (m, 1H), 4.03 (dd, J = 13.0 Hz, 7.0 Hz, 1H), 3.59 (dd, J = 13.5 Hz, 6.0
Hz, 1H), 3.48 (d, J = 7.5 Hz, 1H), 6.08 (s, br, D2O exchangeble, 2H), 8.11 (d, J = 8.0 Hz, 1H), 7.88 (d, J
= 8.5 Hz, 1H), 7.82 (m, 1H), 7.77 (d, J = 7.5 Hz, 2H), 7.67 (m, 2H), 7.58 (d, J = 7.5 Hz, 1H), 7.28 (m,
1H), 7.18 (m, 1H), 6.60 (m, 1H), 6.54 (d, J = 8.0 Hz, 1H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 200.2,
199.9, 199.5 (C=O), 150.5, 142.5, 142.3, 139.4, 136.2, 135.0, 133.1, 130.8, 129.5, 128.5, 122.7, 122.6,
117.9, 117.2, 116.0, 57.3, 40.9, 39.6. MS (ESI): m/z (%) 415 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd
for C25H21NO3: 415.1294; found 415.1280. HPLC-purity 89.4%.
(b) Synthesis of 1,2-diazepines: A mixture of 1,5-diketone (1 mmol) and hydrazine hydrate (3 mmol) was
taken in mortar. The mixture was grounded thoroughly by a pestle for 10-20 min at room temperature. TLC
monitoring, the reaction mixture was worked up by adding water (10 mL) and allowed to stand for 10-15
min. The precipitate was filtered and dried under vacuum. Further purification was accomplished by silica
gel column chromatography using hexane: EtOAc (2:8, v/v) as eluent. The products were obtained in
excellent yields (85-96%).
(2E,5aE)-5-(4-Chlorophenyl)-3-p-tolyl-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one
(4a):
o
Orange solid. Yield: 370 mg (93%). Mp 218-220 C. IR νmax (KBr, cm-1): 3423 (-NH str), 3166, 3121,
3017, 2930 (aromatic C-H str), 1662 (C=O str), 1573, (aromatic, C=C str), 1510, 1394, 1197, 1084, 818,
730. 1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.59 (dd, J = 5.0 Hz, 3.0 Hz, 1H), 3.37 (dd, J = 13.5 Hz, 5.0
Hz, 1H), 3.07 (dd, J = 13.5 Hz, 3.0 Hz, 1H), 2.22 (s, 3H), 8.55 (s, br, D2O exchangble, 1H) 7.47 (d, J =
7.0 Hz, 1H), 7.36 (m, 2H), 7.21 (d, J = 7.0 Hz, 1H), 7.15-7.09 (m, 6H), 6.97 (d, J = 8.0 Hz, 2H).
13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.4 (C=O), 159.4, 154.0, 140.8, 138.5, 136.3, 135.1, 133.0,
131.3, 129.1, 128.3, 127.9, 127.5, 121.7, 115.9, 111.0, 40.7, 39.7, 21.0. MS (ESI): m/z (%): 399 [M+H+].
HRMS-ESI (m/z): [M+H+] calcd for C25H19ClN2O: 399.1264; found 399.1251.
(2E,5aE)-3-(4-Chlorophenyl)-5-(3-nitrophenyl)-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one:
(4b) Orange solid. Yield: 408.5 mg (95%). Mp 235-237 oC. IR νmax (KBr, cm-1): 3434, 3126 (aromatic C-H
str), 1681 (C=O str), 1575 (aromatic, C=C str), 1521, 1398, 1087, 1006, 827. 1H-NMR (CDCl3, 500 MHz)
δ (ppm): 4.70 (dd, J = 5.0 Hz, 2.0 Hz, 1H), 3.42 (dd, J = 13.5 Hz, 5.0 Hz, 1H), 3.07 (dd, J = 13.5 Hz, 3.0 Hz,
1H), 8.86 (s, br, D2O exchangeable, 1H), 7.97 (m, 1H), 7.86 (dd, J = 8.0 Hz, 1.5 Hz, 1H), 7.47 (m, 1H),
13
7.41 (m, 2H), 7.35 (m, 2H), 7.30 (m, 1H), 7.16 (m, 2H), 7.05 (m, 2H). C-NMR (CDCl3, 125 MHz) δ
(ppm): 191.2 (C=O), 158.5, 154.5, 148.2, 145.6, 138.1, 136.7, 133.9, 132.9, 130.9, 130.0, 129.0, 128.1,

HETEROCYCLES, Vol. 85, No. 5, 2012
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127.5, 123.3, 122.7, 122.5, 122.2, 116.4, 109.2, 40.5, 38.1. MS (ESI): m/z (%) 430[M+H+]. HRMS-ESI
(m/z): [M+H+] calcd for C24H16ClN3O3: 430.0958; found 430.0962.
(2E,5aE)-3-(4-Chlorophenyl)-5-phenyl-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one
(4c):
o
Orange solid. Yield: 365.8 mg (95%). Mp 230-232 C. IR νmax (KBr, cm-1): 3414 (-NH str), 3084
1
(aromatic C-H str), 1677 (C=O str), 1559, 1542 (aromatic, C=C str), 1379, 1323, 1079, 821. H-NMR
(CDCl3, 500 MHz) δ (ppm): 4.54 (dd, J = 5.0 Hz, 2.0 Hz, 1H), 3.37 (dd, J = 13.5 Hz, 5.0 Hz, 1H), 3.04
(dd, J = 13.5 Hz, 2.5 Hz, 1H), 8.83 (s, br, D2O exchangble, 1H) 7.42 (dd, J = 7.0 Hz, 1.5 Hz, 1H),
7.32-7.26 (m, 2H), 7.24-7.19 (m, 3H), 7.15-7.07 (m, 5H), 7.04 (d, J = 7.0 Hz, 2H). 13C-NMR (CDCl3, 125
MHz) δ (ppm): 190.3 (C=O), 159.4, 153.2, 141.4, 137.2, 131.9,131.4, 130.3, 129.0, 128.4, 127.9, 127.4,
127.3, 125.5, 120.7, 115.2, 109.1, 39.1, 38.4. MS (ESI): m/z (%) 385 [M+H+]. HRMS-ESI (m/z): [M+H+]
calcd for C24H17ClON2: 385.1108; found 385.1099.
(2E,5aE)-3,5-Bis(4-chlorophenyl)-4,5-dihydroindeno [1,2-c][1,2]diazepin-6(1H)-one (4d): Orange
o
solid. Yield: 394 mg (94%). Mp 215-217 C. IR νmax (KBr, cm-1): 3428 (-NH str), 3175, 3120 (aromatic
1
C-H str), 1673 (C=O str), 1565 (aromatic, C=C str), 1395, 1345, 1080, 810, 769. H-NMR (CDCl3, 500
MHz) δ (ppm): 4.61 (dd, J = 5.0 Hz, 2.5 Hz, 1H), 3.38 (dd, J = 13.5 Hz, 5.0 Hz, 1H), 3.08 (dd, J = 13.5
Hz, 3.0 Hz, 1H), 8.87 (s, br, D2O exchangble, 1H) 7.52 (m, 1H), 7.35 (m, 2H), 7.28 (m, 1H), 7.17 (m, 2H),
7.10-7.05 (m, 6H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.3 (C=O), 159.7, 154.2,142.2, 138.3, 137.3,
135.5, 132.9, 132.6, 131.4, 130.1, 129.1, 129.0, 128.7, 128.5, 127.8, 127.4, 121.9, 116.1, 110.3, 40.1, 39.1.
MS (ESI): m/z (%) 419 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C24H16Cl2N2O: 419.0718; found
419.0711.
(2E,5aE)-3-(4-Bromophenyl)-5-p-tolyl-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one
(4e):
o
Orange solid. Yield: 403 mg (91%). Mp 223-225 C. IR νmax (KBr, cm-1): 3437 (-NH str), 3186, 3128,
3016 (aromatic C-H str), 1665 (C=O str), 1576 (aromatic, C=C str), 1517, 1397, 1335, 1097, 850.
1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.52 (dd, J = 6.0 Hz, 2.50 Hz, 1H), 3.29 (dd, J = 13.5 Hz, 5.0 Hz,
1H), 2.99 (dd, J = 13.5 Hz, 3.0 Hz, 1H), 2.15 (s, 3H), 8.51 (s, br, D2O exchangble, 1H), 7.40 (m, 1H),
7.28 (m,2), 7.23 (m, 2H), 7.12 (m, 1H), 7.02 (m, 2H), 6.96 (dd, J = 7.0 Hz, 1.5 Hz, 2H), 6.90 (d, J = 8.0
Hz, 2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.2 (C=O), 159.3, 153.7, 140.7, 138.4, 138.1, 136.2,
135.6, 134.2, 133.9, 132.9, 131.1, 129.8, 129.0, 128.0, 127.3, 123.4, 121.7, 115.6, 111.0, 40.1, 39.5, 20.9.
MS (ESI): m/z (%) 443 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C25H19BrN2O: 443.0759; found
443.0761.
(2E,5aE)-3-(4-Bromophenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydroindeno[1,2-c][1,2]diazepin-

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o
6(1H)-one (4f): Orange solid. Yield: 467.1 mg (90%). Mp 215-218 C. IR νmax (KBr, cm-1): 3429 (-NH
str), 3166, 3113 (aromatic C-H str), 1671 (C=O str), 1602, 1570 (aromatic, C=C str), 1511, 1391, 1196,
1087, 1014, 905, 847, 715. 1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.49 (m, 1H), 3.64 (s, 3H), 3.61 (s, 6H),
3.05 (m, 1H), 2.94 (m, 1H), 8.83 (s, br, D2O exchangble, 1H) 7.77 (m, 1H), 7.67 (m, 2H), 7.42 (m, 2H),
7.24 (m, 2H), 7.03 (m, 1H), 6.29 (m, 2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.5 (C=O), 159.7,
154.0, 139.6, 138.4, 137.9, 137.1, 135.6, 133.0, 132.0, 130.9, 129.9, 129.2, 128.6, 128.0, 121.8, 116.1,
110.5, 60.8, 56.7, 56.2, 41.2, 39.0. MS (ESI): m/z (%) 519 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for
C27H23BrN2O4: 519.0919; found 519.092.
(2E,5aE)-5-(4-Bromophenyl)-3-phenyl-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one
(4g):
o
Orange solid. Yield: 399 mg (93%). Mp 228-230 C. IR νmax (KBr, cm-1): 3441 (-NH str), 3140, 2922
(aromatic C-H str), 1669 (C=O str), 1600 (aromatic, C=C str), 1398, 1267, 1178, 1086, 1030, 758, 693.
1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.64 (dd, J = 5.0 Hz, 2.5 Hz, 1H), 3.39 (dd, J = 13.5 Hz, 5.0 Hz,
1H), 3.08 (dd, J = 13.5 Hz, 3.0 Hz, 1H), 8.56 (s, br, D2O exchangble, 1H) 7.48 (d, J = 7.0 Hz, 1H), 7.34
(m, 2H), 7.28 (m, 3H), 7.22-7.10 (m, 5H), 6.99 (m, 2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.3
(C=O), 159.4, 154.0, 143.8, 138.5, 138.1, 133.0, 131.3, 131.3, 130.0, 128.5, 128.1, 127.6, 126.9, 123.8,
121.8, 115.8, 110.8, 40.7, 39.6. MS (ESI): m/z (%) 429 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for
C24H17BrN2O: 429.0603; found 429.0595.
(2E,5aE)-3-(4-Bromophenyl)-5-(4-chlorophenyl)-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one
o
(4h): Orange solid. Yield: 444.5 mg (96%). Mp 227-229 C. IR νmax (KBr, cm-1): 3430 (-NH str), 3128
(aromatic C-H str), 1661 (C=O str), 1576, 1521 (aromatic, C=C str), 1399, 1085,1008, 819, 724. 1H-NMR
(CDCl3, 500 MHz) δ (ppm): 4.60 (dd, J = 5.0 Hz, 2.5 Hz, 1H), 3.39 (dd, J = 13.5 Hz, 5.0 Hz, 1H), 3.08
(dd, J = 13.5 Hz, 2.5 Hz, 1H), 8.70 (s, br, D2O exchangble, 1H), 7.49 (m, 1H), 7.35 (m, 2H), 7.28 (m, 2H),
7.21 (m, 1H), 7.17 (m, 2H) 7.14 (m, 2H), 7.08 (m, 2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.5
(C=O), 159.0, 142.7, 138.2, 137.3, 135.5, 132.9, 131.5, 130.1, 129.4, 128.9, 128.4, 127.8, 126.3, 121.9,
120.7, 116.0, 110.2, 40.2, 39.1. MS (ESI): m/z (%) 463 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for
C24H16BrClN2O: 463.0213; found 463.0205.
(2E,5aE)-3,5-Diphenyl-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one (4i): Orange solid. Yield:
337 mg (96%). Mp 158-160 oC. IR νmax (KBr, cm-1): 3436 (-NH str), 3120, 3020 (aromatic C-H str), 1670
1
(C=O str), 1572 (aromatic, C=C str), 1390, 1335, 1196, 1077, 1002, 815, 760. H-NMR (CDCl3, 500
MHz) δ (ppm): 4.66 (dd, J = 5.0 Hz, 2.5 Hz, 1H), 3.44 (dd, J = 13.5 Hz, 5.0 Hz, 1H), 3.10 (dd, J = 13.5
Hz, 2.5 Hz, 1H), 8.80 (s, br, D2O exchangble, 1H) 7.30 (d, J = 7.0 Hz, 1H), 7.28 (m, 4H), 7.21-7.14 (m,
7H), 7.06 (m, 2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.5 (C=O), 154.4, 144.0, 139.4, 138.4, 135.4,

HETEROCYCLES, Vol. 85, No. 5, 2012
1173
135.3, 133.2, 131.3, 130.1, 129.8, 128.9, 128.6, 127.8, 127.5, 126.7, 125.6, 122.9, 116.3, 110.5, 40.8, 40.0.
MS (ESI): m/z (%) 351 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C24H18N2O: 351.1457; found
351.1452.
(2E,5aE)-3-Phenyl-5-p-tolyl-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one (4j): Orange solid.
o
Yield: 343 mg (94%). Mp 212-214 C. IR νmax (KBr, cm-1): 3397 (-NH str), 3196, 2985 (aromatic C-H
str), 1665 (C=O str), 1591 (aromatic, C=C str), 1400, 1257, 1082, 813, 760. 1H-NMR (CDCl3, 500 MHz)
δ (ppm): 4.58 (dd, J = 5.0 Hz, 2.0 Hz, 1H), 3.43 (dd, J = 13.5 Hz, 5.0 Hz, 1H), 3.09 (dd, J = 13.5 Hz, 2.5
Hz, 1H), 2.20 (s, 3H), 8.75 (s, br, D2O exchangble, 1H), 7.45 (dd, J = 6.0 Hz, 2.5 Hz, 1H), 7.30 (m, 2H),
7.23 (m, 2H), 7.20 (m, 2H), 7.17 (m, 1H), 7.13 (m, 3H), 6.96 (m, 2H). 13C-NMR (CDCl3, 125 MHz) δ
(ppm): 191.3 (C=O), 160.7, 154.0, 141.0, 139.3, 138.6, 136.1, 133.1, 132.7, 131.2, 129.1, 128.5, 128.4,
127.5, 126.6, 121.7, 115.8, 111.1, 40.3, 40.0, 21.0. MS (ESI): m/z (%) 365 [M+H+]. HRMS-ESI (m/z):
[M+H+] calcd for C25H20N2O: 365.1654; found 365.1645.
(2E,5aE)-5-(4-Chlorophenyl)-3-phenyl-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one
(4k):
o
Orange solid. Yield: 365.7 mg (95%). Mp 232-234 C. IR νmax (KBr, cm-1): 3424 (-NH str), 3091
1
(aromatic C-H str), 1675 (C=O str), 1565, 1531 (aromatic, C=C str), 1389, 1324, 1090, 817. H-NMR
(CDCl3, 500 MHz) δ (ppm): 4.55 (dd, J = 5.0 Hz, 2.0 Hz, 1H), 3.38 (dd, J = 13.5 Hz, 5.0 Hz, 1H), 3.03
(dd, J = 13.5 Hz, 2.5 Hz, 1H), 8.82 (s, br, D2O exchangble, 1H) 7.41 (dd, J = 7.0 Hz, 1.5 Hz, 1H),
7.39-7.24 (m, 3H), 7.23-7.18 (m, 4H), 7.14-7.06 (m, 5H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 190.3
(C=O), 159.5, 153.2, 141.3, 137.9, 137.2, 132.0, 131.4, 130.3, 129.0, 128.4, 128.0, 127.5, 127.3,125.5,
120.7, 115.2, 109.1, 39.1, 38.4. MS (ESI): m/z (%) 385 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for
C24H17ClN2O: 385.1108; found 385.1114.
(2E,5aE)-5-(3-Nitrophenyl)-3-phenyl-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one (4l): Orange
o
solid. Yield: 360.4 mg (91%). Mp 231-233 C. IR νmax (KBr, cm-1): 3433 (-NH str), 3175, 3122, 3017
(aromatic C-H str), 1682 (C=O str), 1573 (aromatic, C=C str), 1510, 1394, 1333, 1197, 1085, 1004, 889,
732.1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.76 (dd, J = 5.0 Hz, 2.5 Hz, 1H), 3.56 (dd, J = 13.5 Hz, 5.0
Hz, 1H), 3.17 (dd, J = 13.5 Hz, 3.0 Hz, 1H), 8.78 (s, br, D2O exchangble, 1H), 8.06 (d, J = 7.0 Hz, 1H),
7.91 (m, 1H), 7.56 (d, J = 7.5 Hz, 1H), 7.49 (m, 1H), 7.41 (m, 2H), 7.37 (m, 2H), 7.30 (m, 1H), 7.28 (m,
1H), 7.24 (m, 2H), 7.17 (m, 1H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 192.0 (C=O), 157.0, 144.9, 138.5,
132.8, 131.9, 130.3, 129.8, 129.5, 128.6, 128.4, 127.1, 126.7, 126.2, 125.8, 123.8, 123.4, 122.7, 115.5,
111.2, 40.8, 38.9. MS (ESI): m/z (%) 396 [M+H+] HRMS-ESI (m/z): [M+H+] calcd for C24H17N3O3:
396.1348; found 396.1344.
(2E,5aE)-3-(4-Nitrophenyl)-5-phenyl-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one (4m): Orange

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o
solid. Yield: 364.3 mg (92%). Mp 234-236 C. IR νmax (KBr, cm-1): 3456 (-NH str), 3121, 3025, 2917
(aromatic C-H str), 1691 (C=O str), 1572 (aromatic, C=C str), 1514, 1391, 1335, 1200, 1076, 1001, 816,
713. 1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.62 (dd, J = 5.0 Hz, 2.5 Hz, 1H), 3.36 (dd, J = 13.0 Hz, 5.0
Hz, 1H), 3.03 (dd, J = 13.5 Hz, 3.0 Hz, 1H), 8.66 (s, br, D2O exchangble, 1H), 8.12 (d, J=8.0 Hz, 1H),
7.92 (m, 2H), 7.77 (m, 1H), 7.73 (m, 1H), 7.43 (d, J = 7.0 Hz, 1H), 7.19 (m, 2H), 7.10 (m, 3H), 7.01 (m,
2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.4 (C=O), 157.6, 145.1, 138.4, 132.7, 131.6, 130.1, 128.8,
128.7, 128.5, 127.6, 127.3, 125.9, 123.7, 123.3, 122.1, 115.9, 111.5, 40.8, 39.7. MS (ESI): m/z (%) 396
[M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C24H17N3O3: 396.1348; found 396.1345.
(2E,5aE)-3-(4-Nitrophenyl)-5-p-tolyl-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one (4n): Orange
o
solid. Yield: 377.2 mg (92%). Mp 239-241 C. IR νmax (KBr, cm-1): 3419 (-NH str), 3112 (aromatic C-H
str), 1690 (C=O str), 1576 (aromatic, C=C str), 1398, 1080, 997, 893, 823. 1H-NMR (CDCl3, 500 MHz) δ
(ppm): 4.57 (dd, J = 5.0 Hz, 2.0 Hz, 1H), 3.33 (dd, J = 13.5 Hz, 5.0 Hz, 1H), 3.01 (dd, J = 13.5 Hz, 2.5
Hz, 1H), 2.10 (s, 3H), 8.71 (s, br, D2O exchangble, 1H) 7.94 (m, 2H), 7.32 (m, 2H), 7.28 (m, 4H), 6.98
(m, 2H), 6.90 (m, 2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.4 (C=O), 157.7, 147.7, 145.3, 140.8,
138.4, 136.6, 132.7, 131.5, 130.0, 129.3, 128.0, 127.4, 127.3, 123.3, 122.0, 115.9, 111.8, 40.4, 39.1, 21.0.
MS (ESI): m/z (%) 410 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C25H19N3O3: 410.1505; found
410.1502.
(2E,5aE)-5-(4-Chlorophenyl)-3-(2-hydroxyphenyl)-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one
o
(4o): Orange solid. Yield: 356.9 mg (89%). Mp 212-214 C. IR νmax (KBr, cm-1): 3435 (-NH str), 3128,
2979 (aromatic C-H str), 1673 (C=O str), 1613, 1571 (aromatic, C=C str), 1498, 1398, 1249, 1195, 1086,
753. 1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.19 (dd, J = 9.0 Hz, 5.0 Hz, 1H), 3.64 (dd, J = 14.0 Hz, 9.0
Hz, 1H), 3.29 (dd, J = 14.0 Hz, 6.5 Hz, 1H), 11.83 (s, br, D2O exchangble, 1H), 8.41 (s, br, D2O
exchangble, 1H), 7.43 (dd, J = 8.5 Hz, 2.0 Hz, 2H), 7.38 (m, 1H), 7.08 (m, 4H), 7.03 (m, 2H), 6.99 (m,
1H), 6.71 (m, 1H), 6.65 (m, 1H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.0 (C=O), 164.1, 157.9,
154.6, 139.5, 138.3, 137.3, 132.7, 132.0, 129.7, 129.4, 128.9, 128.2, 127.6, 126.1, 121.3, 119.7, 118.9,
118.0, 117.8, 40.3, 38.2. MS (ESI): m/z (%) 401 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for
C24H17ClN2O2: 401.1057; found 401.1060.
(2E,5aE)-3-(2-Hydroxyphenyl)-5-(3-nitrophenyl)-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one
o
(4p): Orange solid. Yield: 350 mg (85%). Mp 224-226 C. IR νmax (KBr, cm-1): 3420 (-NH str), 3101,
2981 (aromatic C-H str), 1675 (C=O str), 1571 (aromatic, C=C str), 1493, 1391, 1232, 1180, 1056, 864,
782. 1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.24 (dd, J = 13.0 Hz, 4.0 Hz, 1H), 3.52 (dd, J = 13.0 Hz, 5.0
Hz, 1H), 3.19 (dd, J = 14.0 Hz, 5.0 Hz, 1H), 11.59 (s, br, D2O exchangble, 1H), 8.35 (s, br, D2O

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exchangble, 1H ), 8.10 (m, 1H), 7.83 (m, 2H), 7.41 (m, 1H), 7.27 (m, 2H), 7.11 (m, 2H), 7.03 (m, 1H),
13
6.95 (m, 1H), 6.73 (m, 1H), 6.60 (m, 1H). C-NMR (CDCl3, 125 MHz) δ (ppm): 190.9 (C=O), 164.1,
157.7, 153.7, 139.6, 138.2, 137.4, 133.4, 132.2, 129.6, 129.1, 128.8, 128.1, 127.7, 126.3, 125.2, 122.1,
119.8, 118.9, 117.9, 40.2, 39.2. MS (ESI): m/z (%) 412 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for
C24H17N3O4: 412.1297; found 412.1291.
(2E,5aE)-3-(2-Hydroxyphenyl)-5-p-tolyl-4,5-dihydroindeno[1,2-c][1,2]diazepin-6(1H)-one
(4q):
o
Orange solid. Yield: 331.5 mg (87%). Mp 208-210 C. IR νmax (KBr, cm-1): 3432 (-NH str), 3181, 3117,
2965 (aromatic C-H str), 1670 (C=O str), 1609, 1560 (aromatic, C=C str), 1449, 1389, 1249, 1195, 761.
1H-NMR (CDCl3, 500 MHz) δ (ppm): 4.48 (dd, J = 5.0 Hz, 2.0 Hz, 1H), 3.60 (dd, J = 13.5 Hz, 5.0 Hz,
1H), 2.90 (dd, J = 14.0 Hz, 7.0 Hz, 1H), 2.05 (s, 3H), 11.69 (s, br, D2O exchangble, 1H ), 8.52 (s, br, D2O
exchangble, 1H ), 7.50 (d, J = 7.0 Hz, 1H), 7.34 (m, 1H), 7.28 (m, 2H), 6.99 (m, 3H), 6.83 (m, 3H), 6.63
(m, 1H), 6.45 (m, 1H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.9 (C=O), 164.0, 158.2, 154.8, 139.9,
138.3, 136.3, 132.6, 131.4, 129.9, 129.1, 128.2, 127.5, 127.4, 121.6, 119.7, 118.8, 117.2, 116.5, 40.5, 37.5,
20.9. MS (ESI): m/z (%) 381 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C25H20N2O2: 381.1603; found
381.1595.
(2E,5aE)-3-(2-Hydroxyphenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydroindeno[1,2-c][1,2]diazepin-
6(1H)-one (4r): Orange solid. Yield: 411 mg (90%). Mp 238-240 oC. IR νmax (KBr, cm-1): 3436 (-NH str),
1
3134, 2968 (aromatic C-H str), 1665 (C=O str), 1625 (aromatic, C=C str), 1524, 1399, 1089. H-NMR
(CDCl3, 500 MHz) δ (ppm): 4.58 (dd, J = 5.0 Hz, 2.5 Hz, 1H), 3.67 (s, 6H), 3.65 (s, 3H), 3.59 (dd, J =
13.5 Hz, 5.0 Hz, 1H), 3.07 (dd, J = 13.5 Hz, 2.5 Hz, 1H), 11.82 (s, br, D2O exchangble, 1H), 8.45 (s, br,
D2O exchangble, 1H) 7.50 (d, J = 6.5 Hz, 1H), 7.42 (td, 1H), 7.37 (m, 1H), 7.28 (d, J = 7.0 Hz, 1H), 7.14
(td, 1H), 6.86 (m, 2H), 6.60 (m, 1H), 6.43 (s, 2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 191.4 (C=O),
162.2, 154.9, 152.5, 151.8, 140.4, 139.8, 138.5, 136.0, 133.2, 129.2, 128.4, 128.0, 127.3, 126.5, 122.3,
119.1, 118.5, 117.7, 117.3, 60.2, 56.6, 40.3, 39.8. MS (ESI): m/z (%) 457 [M+H+]. HRMS-ESI (m/z):
[M+H+] calcd for C27H24N2O5: 457.1763; found 457.1755.
(c) Synthesis of 1,2-oxazepines: To a stirred solution of 1,5-diketone (1 mmol) in EtOH (0.5 mL) was
added hydroxylamine hydrochloride (2 mmol) and aq. NaOH (1M, 2-3 mL). The reaction mixture was
refluxed for 2-3 h. TLC monitoring; the reaction mixture was worked up by neutralizing with HCl (0.5M,
2-3 mL) dropwise addition, followed by water addition (10 mL). The precipitate was filtered and dried
under reduced pressure. Further purification was accomplished by silica gel column chromatography using
hexane: EtOAc (1:9, v/v) as eluent. The products were obtained in excellent yields (85-88%).

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(2E,5aE)-3-(4-Bromophenyl)-5-p-tolyl-4,5-dihydroindeno[2,1-f][1,2]oxazepin-6-one (5a): White solid.
Yield: 377.4 mg (85%). Mp 97-99 °C. IR νmax (KBr, cm-1): 3127, 2917 (aromatic C-H str), 1673 (C=O str),
1584, 1391, 1015, 854, 742. 1H-NMR (CDCl3, 500 MHz) δ (ppm): 5.72 (dd, J = 10.0 Hz, 3.0 Hz, 1H), 3.73
(m, 1H), 3.32 (dd, J = 12.5 Hz, 8.5 Hz, 1H), 2.23 (s, 3H), 7.83 (dd, J = 6.0 Hz, 2.0 Hz, 1H), 7.77 (d, J = 7.0
Hz, 2H), 7.69 (m, 2H), 7.53 (dd, J = 6.0 Hz, 2.0 Hz, 1H), 7.39 (m, 1H), 7.23 (m, 1H), 7.04 (m, 2H), 6.89 (m,
2H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 192.7 (C=O), 158.5, 154.9, 140.3, 138.2, 132.5, 132.2, 131.9,
129.4, 128.3, 128.1, 127.1, 126.6, 125.8, 124.3, 121.9, 116.1, 109.2, 42.7, 39.6, 21.1. MS (ESI): m/z (%)
444 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C25H18BrNO2: 444.0599; found 444.0587.
(2E,5aE)-3-(4-Bromophenyl)-5-phenyl-4,5-dihydroindeno[2,1-f][1,2]oxazepin-6-one (5b): White solid.
Yield: 378.4 mg (88%). Mp 104-106 °C. IR νmax (KBr, cm-1): 2925 (aromatic C-H str), 1685 (C=O str),
1569, 1399, 1071, 1012, 902, 827, 757. 1H-NMR (CDCl3, 500 MHz) δ (ppm): 5.68 (dd, J = 8.5 Hz, 2.5 Hz,
1H), 3.66 (dd, J = 12.5 Hz, 8.5 Hz, 1H), 3.24 (dd, J = 13.0 Hz, 8.0 Hz, 1H), 7.53-7.44 (m, 5H), 7.35-7.22 (m,
6H), 7.18 (m, 1H). 13C-NMR (CDCl3, 125 MHz) δ (ppm): 193.1 (C=O), 158.6, 155.2, 140.6, 138.4, 132.3,
132.1, 131.9, 128.8, 128.4, 128.1, 127.2, 126.8, 125.8, 124.4, 122.1, 115.9, 108.3, 42.9, 39.6. MS (ESI):
m/z (%) 430 [M+H+]. HRMS-ESI (m/z): [M+H+] calcd for C24H16BrNO2: 430.0443; found 430.0440.
ACKNOWLEDGEMENT
We thank Department of Chemistry, IIT Roorkee through MHRD, New Delhi for financial support.
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