Alternate synthesis route of 2-(substituted phenyl)-3,3a-dihydro-8H- pyrazolo[5,1-a[isoindol-8-ones via chalcone-based n-formyl-pyrazolines

Article abstract of DOI:10.1080/00397911.2011.606414

An alternate approach to 2-(substituted phenyl)-3,3a-dihydro-8H-pyrazolo[5, l-a] isoindol-8-ones via chalcone-based N-formyl-pyrazolines is described. N-Formyl-pyrazolines were prepared in excellent yield (81-96%) by the reaction of chalcones with hydrazine hydrate in the presence of formic acid, which undergoes intramolecular Friedel-Crafts acylation in the presence of trifluoroacetic acid (TFA) as a catalyst to afford functionalized 2-(substituted phenyl)-3,3a-dihydro-8H-pyrazolo[5,1-a]isoindol-8-ones in good to excellent yield (74-94%) at reflux in acetonitrile. Our synthetic route avoids expensive reagents and significantly improves yields.

Full text of DOI:10.1080/00397911.2011.606414

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Alternate Synthesis Route of 2-
(Substituted Phenyl)-3,3a-dihydro-8H-
pyrazolo[5,1-a]isoindol-8-ones via
Chalcone-Based N-Formyl-pyrazolines
Naseem Ahmed a & Dharm Dev a
a Department of Chemistry, Indian Institute of Technology Roorkee,
Roorkee, Uttarakhand, India
Accepted author version posted online: 21 Feb 2012.Version of
record first published: 13 Nov 2012.
To cite this article: Naseem Ahmed & Dharm Dev (2013): Alternate Synthesis Route of 2-(Substituted
Phenyl)-3,3a-dihydro-8H-pyrazolo[5,1-a]isoindol-8-ones via Chalcone-Based N-Formyl-pyrazolines,
Synthetic Communications: An International Journal for Rapid Communication of Synthetic Organic
Chemistry, 43:5, 689-704
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Synthetic Communications1, 43: 689–704, 2013
Copyright # Taylor & Francis Group, LLC
ISSN: 0039-7911 print=1532-2432 online
DOI: 10.1080/00397911.2011.606414
ALTERNATE SYNTHESIS ROUTE OF 2-(SUBSTITUTED
PHENYL)-3,3a-DIHYDRO-8H-PYRAZOLO[5,1-
a]ISOINDOL-8-ONES VIA CHALCONE-BASED
N-FORMYL-PYRAZOLINES
Naseem Ahmed and Dharm Dev
Department of Chemistry, Indian Institute of Technology Roorkee, Roorkee,
Uttarakhand, India
GRAPHICAL ABSTRACT
Abstract An alternate approach to 2-(substituted phenyl)-3,3a-dihydro-8H-pyrazolo[5,l-a]
isoindol-8-ones via chalcone-based N-formyl-pyrazolines is described. N-Formyl-
pyrazolines were prepared in excellent yield (81–96%) by the reaction of chalcones with
hydrazine hydrate in the presence of formic acid, which undergoes intramolecular
Friedel–Crafts acylation in the presence of trifluoroacetic acid (TFA) as a catalyst to
afford functionalized 2-(substituted phenyl)-3,3a-dihydro-8H-pyrazolo[5,1-a]isoindol-8-
ones in good to excellent yield (74–94%) at reflux in acetonitrile. Our synthetic route
avoids expensive reagents and significantly improves yields.
Keywords Chalcone N-formyl-2-pyrazoline; Friedel–Crafts acylation; 2-(substituted
phenyl)-3,3a-dihydro-8H-pyrazolo[5,l-a]isoindol-8-ones
INTRODUCTION
Substituted pyrazoloisoindoles are common structural intermediates in the
biogenesis of naturally occurring plant-growth regulants[1] and are widely used for
the synthesis of antiamoebic[2] and antidepressant molecules.[3] Pyrazoloisoindolones
are stable molecules but are quite susceptible to nucleophilic attack at the lactam
function and cleaved to give 2-[3(5)-arylpyrazol-3(5)-yl]benzoic acid in aqueous
bases that include alcohols or amines.[4] The reverse cyclization of
Received June 2, 2011.
Address correspondence to Naseem Ahmed, Department of Chemistry, Indian Institute of
Technology Roorkee, Roorkee 247667, Uttarakhand, India. E-mail: nasemfcy@iitr.ernet.in
689

690
N. AHMED AND D. DEV
Scheme 1. Synthesis of N-formyl-pyrozolines and pyrazoloisoindoles.
2-[3(5)-arylpyrazol-3(5)-yl]benzoic acid proceeded with thionyl chloride, phosphorus
oxychloride, or acetic anhydride.[5]
Functionalized N-formyl-pyrazoline intermediates are also important because
of their application in heterocyclic synthesis of pyrazoloisoindoles and many med-
icinal moieties.[2] The reaction of hydrazine and its derivatives with a,b-unsaturated
ketones is one of the preparative methods for the regioselective synthesis of pyrazo-
lines.[6–14] The pyrazoline derivatives showed a wide spectrum of biological activity
such antibacterial, antifungal, anti-inflammatory, antidepressent, and anticonvulsant
activities.[15–19]
Based on these applications, different strategies for their synthesis have been
reported.[20–23] Pyrazoloisoindoles have been synthesized by the condensation of
phthalaldehydic acid and acetophenones under basic reaction conditions, which gave
phenacyl phthalides, followed by the reaction of hydrazine hydrate or its derivatives
in water at reflux temperature, which gave the pyrazoloisoindole derivatives
(Scheme 1).[20]
Similarly, other synthetic routes were also reported by the reaction of imino-
phosphoranes with acetylenic compounds[21] and intramolecular Wittig reaction of
phosphorus ylides.[22] These methods gave access to a variety of 2- and=or 3-alkyl
and phenyl substituted pyrazoloisoindolones.[23] However, the use of expensive
reagents, poor yields, strong acid=base conditions, high temperature, and prolonged
reaction time were major drawbacks. To address these concerns as a part of a syn-
thetic approach, it often required to use an alternative synthetic strategy. Herein, we
report an alternate method for the preparation of functionalized 2-(substituted
phenyl)-3,3a-dihydro-8H-pyrazolo[5,1-a]isoindol-8-one (3a–o) via chalcone-based
N-formyl-pyrazolines using trifluoroacetic acid as catalyst at reflux in acetonitrile
(Scheme 2). In comparison with other methods, our method gave significantly better
Scheme 2. Alternate synthesis route of N-formylpyrozolines and pyrazoloisoindoles.

CHALCONE-BASED N-FORMYL-PYRAZOLINES
691
yield (74–94%) and avoids the use of expensive reagents. The catalytic efficiency of
many other protic acids such as concentrated HCl, H2SO4, HClO4, and AcOH were
tested to further improve yields of the product.[24–26] However, these acids failed to
give the product even at elevated temperature and prolonged reaction time.
RESULTS AND DISCUSSION
Using various aldehydes and acetophenones under condensation reaction
afforded 1,3-diaryl-2-propen-l-ones (chalcones) (reported in the experimental sec-
tion).[24–26] The reaction of chalcones (1a–p) and hydrazine hydrate dissolved in
the solvent (formic acid) at reflux gave N-formyl-pyrazolines (2a–o) in excellent yield
(81–95%) (Table 2). Compound 1p failed to give the product, which might be due to
the influence of 2-amino substituent on the aromatic ring. Conversely, 2-hydroxy
substituents (1k and 1n) gave better yields. N-Formyl-pyrazolines (2a–o) in the pres-
ence of trifluoroacetic acid (TFA) as catalyst in acetonitrile at reflux temperature
undergo intramolecular Friedel–Crafts acylation to afford 2-(substituted
phenyl)-3,3a-dihydropyrazolo[5,1-a]isoindol-8-ones (3a–o) in good to excellent yields
(74–94%). The assigned structure of chalcones, N-formyl-pyrazolines, and 2-(substi-
tuted phenyl)-3,3a-dihydropyrazolo[5,1-a]isoindol-8-ones were confirmed on the
basis of their spectral analysis [Fourier transform–infrared (FT-IR), 1H NMR,
13C NMR, and gas chromatography–high-resolution mass spectrometry (GC MS=
HRMS)] and further compared with reported values in the literature.[4,26] For
example, 2-phenyl-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one (3a) was characterized
on the basis of spectral analysis that included FT-IR spectrum in vmax(KBr, cmꢀ1),
1
=
=
which gave strong bands for C O at 1692, C N at 1471, and C-N at 1183. In the H
NMR spectrum in d (ppm), an ABX pattern was observed where Hax(A), Heq(B), and
Hax(X) appear as double doublets at 3.16–3.20, 3.70–3.76, and 5.52ꢀ5.56 with
JAB ¼ 17.5 Hz, JAX ¼ 4.5 Hz, and JBX ¼ 11.5 Hz, respectively. Nine aromatic protons
were observed between 7.16 and 7.72 ppm (Fig. 1, Table 1). 13C NMR spectrum in d
(ppm) shows the presence of a methylene carbon at 40.7, a methine carbon at 60.3,
=
C N at 138.4, and a ketonic carbon at 156.8 ppm. The signal intensity between d
124.5 and 131.0 ppm corresponds to 12 aromatic carbons (Table 1). HRMS showed
molecular ion (m=z) at 248.0950 [Mþ], further confirming the product.
Similarly, compound 2a was also characterized on the basis of spectral analysis
that included FT-IR spectrum in vmax (KBr, cmꢀ1), which gave strong bands for
1
=
=
C O at 1656, C N at 1602, and C-N at 1142. In the H NMR spectrum in d
(ppm), an ABX-type pattern was observed where Hax(A), Heq(B), and Hax(X) appear
as double doublets at 3.21–3.25, 3.79–3.85, and 5.53–5.50 with JAB ¼ 17.5 Hz,
JAX ¼ 4.5 Hz, and JBX ¼ 12.0 Hz, respectively. Ten aromatic protons were observed
between 7.03 and 7.76 and the formyl proton was a singlet at 8.9 ppm (Fig. 1,
Table 1). 13C NMR spectrum d (ppm) revealed the presence of a methylene carbon
=
at 42.4, methine carbon at 58.8, C N carbon at 140.4, and aldehyde carbon at
159.9 ppm. The signal intensity between 123.0 and 131.0 ppm corresponds to 12 aro-
matic carbons (Table 1). GC-MS showed molecular ions (m=z) at 250 [Mþ], further
confirming the assigned structure. Similarly, other products (3b–3o and their inter-
mediates 2b–2o) were characterized on the basis of their spectral values reported,
in the experimental section. In the case of 3h and 3o, two regioisomers are possible,

692
N. AHMED AND D. DEV
Figure 1. N-Formyl-pyrazolines (2a) and 2-(phenyl)-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one (3a).
but only one is obtained and confirmed by 1H NMR values. This can be explained on
the basis of ortho=para (electron-rich carbon) ratio, which is 2:1. Therefore, the
ortho-position has twice the probability of the para-position and is more suitable
to give a less-strained ring.
The structures of the heteroaromatic tricyclic ketones obtained as well as the
yields are depicted in Table 2. A mechanistic proposal to account for the formation
of the ketones from the aldehydes is outlined in Scheme 2. Two alternative pathways
are compatible with the observed effect of additional substituents on the aromatic
rings and with the possible occurrence of competing aromatic iodination when elec-
tronically activated aromatic rings are present; this side reaction has been observed
for some substrates.
Table 1. 1H and 13CNMR spectral data of 2a and 3a
2a d
(ppm)
3a d
(ppm)
H
2a d (ppm)
3.22 (1H,dd,
H
3a d (ppm)
C
3
C
4eq
3.19 (1H, dd,
J4eq, 4ax17.5,
155.59
42.45
58.84
138.47
40.76
60.33
J4eq, 4ax 17.5,
J4eq, 5ax 4.5 Hz)
3.82 (1H, dd,
J4eq, 4ax 17.5,
J4ax, 5ax 12.0 Hz)
5.54 (1H, dd,
J4eq, 5ax 4.5,
J4eq, 5ax 4.5 Hz)
3.74 (1H, dd,
J4eq,4ax17.5,
4ax
4
5
J4ax, 5ax 11.5 Hz)
5.54 (1H, dd,
J4eq,5ax 4.5,
5ax
J4ax, 5ax 12.0 Hz)
Ar-2,6 7.29–7.25 (2H, m)
Ar-3,5 7.45–7.42 (2H, m)
J4ax, 5ax 11.5 Hz)
7.18–7.16 (1H, m)
Ar-4,5 7.41–7.36 (2H, m)
Ar-2
Ar-1
Ar-2,6
Ar-3,5
Ar-4
140.40
126.51
128.65
130.49
131.02
126.19
127.85
130.32
156.87
Ar-2,6
Ar-3,5
Ar-3
Ar0-4
7.72–7.70 (1H, m)
7.18–7.16 (1H, m)
Ar-4
7.29–7.25 (1H, m)
Ar0-2,6 7.75–7.73 (2H, m)
Ar0-3,5 7.29–7.22 (2H, m)
Ar0-2,6
7.72–7.70 (2H, m)
N-CHO 159.92 N-CO
Ar0-3,5 7.29–7.25 (2H, m)
Ar0-4
N-CHO 8.97 (1H, s)
7.29–7.25 (1H, m)
Ar0-1
Ar0-2,6
Ar0-3,5
Ar0-4
130.70
128.86
125.47
127.82
129.03
128.15
124.55
127.37

CHALCONE-BASED N-FORMYL-PYRAZOLINES
693
Table 2. Synthesis of 2-(sustitutedphenyl)-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one and N-formyl-
pyrazolines from chalconesa
Chalcone
N-Formyl-pyrazoline
Yield (%)
Pyrazoloisoindole
Yield (%)
96
94
95
95
94
90
93
89
93
92
90
89
91
93
87
88
(Continued )

694
N. AHMED AND D. DEV
Table 2. Continued
Chalcone
N-Formyl-pyrazoline
Yield (%)
Pyrazoloisoindole
Yield (%)
93
87
94
90
87
85
83
78
76
75
85
81
74
75
0b
—
aAll reactions were carried out according to the general procedure.
bYields refer to isolated products.

CHALCONE-BASED N-FORMYL-PYRAZOLINES
695
Scheme 3. A plausible mechanism that accounts for the observed pyrazoloisoindole formation.
Alternatively, as outlined in the right-hand part of Scheme 2, a direct addition
of the arene to the activated carbonyl group cannot be ruled out at present. Sub-
sequent loss of HI would give the ketone and would also account for the need for
a second equivalent of the iodinating reagent. Both mechanistic pathways are plaus-
ible and compatible with the formation of the observed products and the available
information on the process.
In short, a new reaction promoted by the presence of iodonium ions has been
reported. The reaction makes it possible to use aldehydes as acylating agents for are-
nes in a straightforward synthesis of ketones.[27]
The substitution effect on aromatic rings has shown influence on product yields
and reaction time. For example, without substituent, N-formyl-pyrazoline (2a) gave
better yield (94%) in shorter reaction time (10 h). Having an electron-donating sub-
stituent such as Cl, Br, OCH3, and CH3 on N-formyl-pyrazolines (2b–2j) gave almost
the same yield (87–93%) but took longer reaction time (16 h). Conversely, a substitu-
ent such as (OH, NO2) on N-formyl-pyrazolines (2k–2p) gave less yield (74–78%) in
longer reaction time (20 h). A substituent such as (NH2) on 20-aminochalcone (1p)
failed to give the product 2p, even prolonging the reaction time (Table 2).
CONCLUSION
In conclusion, we have reported an alternate and high-yielding synthetic route
for functionalized pyrazoloisoindoles and N-formyl-pyrazolines from chalcones in
excellent yields (74–94% and 81–96%, respectively). In pyrazoloisoindole synthesis,
trifluoroacetic acid (TFA) was an efficient catalyst for intramolecular Friedel–Crafts
acylation at reflux in acetonitrile. Our synthetic route avoids use of expensive
reagents and significantly improves yields.
EXPERIMENTAL
Organic solvents were dried by standard methods when necessary. Commer-
cially available reagents were used without further purification unless mentioned.
All reactions were monitored by thin-layer correspondence (TLC) using precoated

696
N. AHMED AND D. DEV
silica-gel aluminum plates. Visualization of TLC plates was accomplished with an
ultraviolet (UV) lamp or in an iodine chamber. The column chromatography
was performed using silica gel (100–200 mesh, SD Fine-Chem Limited) with ethyl
acetate=hexane as eluent system. Melting points were recorded on a perfit apparatus
and are uncorrected. The IR spectrum was recorded with KBr on a Thomso Nicolet
1
FT-IR spectrophotometer. H and 13C NMR spectra were obtained in CDCl3 on a
Bruker Spectrospin 500=125-MHz spectrometer using tetramethylsilane (TMS) as
1
internal standard. Chemical shifts of H NMR spectra were given in parts per mil-
lion with respect to TMS, and the coupling constant J was measured in hertz. 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). GC-MS=HRMS spectra
were recorded on a Perkin-Elmer Clarus-500=Bruker instrument.
Synthesis of N-Formylpyrazoline
General procedure. Chalcones (1.00 mmol), hydrazine hydrate (0.55 mmol),
and formic acid (5 mL) were heated at reflux for 3–4 h. After completion of the reac-
tion as indicated by TLC, the reaction mixture was poured into crushed ice. The pre-
cipitate was separated by filtration, washed with water under reduced pressure, and
recrystallized from methanol to obtain the N-formyl-pyrazolines (2a–2o) in 81–96%
yield.
3,5-Diphenyl-4,5-dihydropyrazole-1-carbaldehyde (2a). Yield: 96%;
1
white powder mp: 140–142 ꢁC; H NMR (CDCl3, 500 MHz) d (ppm): 8.97 (s, 1H),
7.75–7.73 (m, 2H), 7.45–7.42 (m, 3H), 7.36–7.28 (m, 5H), 5.54 (dd, J ¼ 4.5,
12.0 Hz, 1H), 3.82 (dd, J ¼ 12.0, 16.0 Hz, 1H), 3.22 (dd, J ¼ 4.5, 16.0 Hz, 1H); 13C
NMR (CDCl3, 125 MHz) d (ppm): 159.9, 155.5, 140.4, 130.7, 130.4, 128.8 (2C),
128.6 (2C), 127.8, 126.5 (2C), 125.4 (2C), 58.8, 42.4; IR vmax (KBr, cmꢀ1): 1656,
1605, 1424, 1383, 1329, 1262, 1142, 904, 764, 696, 536; GCMS (m=z) ¼ 250 [Mþ,
C16H14N2O], 222, 221, 145 (100%), 119, 114, 77, 65, 51.
5-(4-Chlorophenyl)-3-phenyl-4,5-dihydropyrazole-1-carbaldehyde (2b).
1
Yield: 95%; white solid mp: 102–104 ꢁC; H NMR (CDCl3, 500 MHz) d (ppm):
8.98 (s, 1H), 7.74 (d, J ¼ 6.0 Hz, 2H), 7.46–7.43 (m, 3H), 7.32–7.30 (m, 2H), 7.21
(d, J ¼ 7.0 Hz, 2H), 5.50 (dd, J ¼ 4.5, 11.5 Hz, 1H), 3.82 (dd, J ¼ 11.5, 17.5 Hz,
1H), 3.21 (dd, J ¼ 4.5, 16.9 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 160.2,
152.5, 135.4, 131.7, 130.0, 128.8 (2C), 128.4 (2C), 127.3, 125.6 (2C), 125.6 (2C),
59.2, 40.0; IR vmax (KBr, cmꢀ1): 1664, 1604, 1494, 1421, 1326, 1241, 1089, 1026,
823, 755; GCMS (m=z) ¼ 284 [Mþ., C16H13ClN2O], 286, 285, 255, 249, 207, 178,
97, 65, 51.
3,5-Bis(4-chlorophenyl)-4,5-dihydropyrazole-1-carbaldehyde (2c). Yield:
95%; white solid; mp: 145–146 ꢁC; 1H NMR (CDCl3, 500 MHz) d (ppm): 8.93 (s, 1H),
7.68–7.65(m, 2H), 7.42–7.40 (m, 2H), 7.33–7.30 (m, 2H), 7.19–7.17 (m, 2H), 5.50 (dd,
J ¼ 5.0, 12.0 Hz, 1H), 3.80 (dd, J ¼ 11.5, 17.5 Hz, 1H), 3.16 (dd, J ¼ 5.5, 16.0 Hz, 1H);
13C NMR (CDCl3, 125 MHz) d (ppm): 160.1, 153.8, 132.9, 131.0, 131.0, 130.1, 128.1
(2C), 125.9 (2C), 124.3 (2C), 123.9 (2C), 59.0, 40.8; IR vmax (KBr, cmꢀ1): 1676, 1616,
1480, 1426, 1314, 1251, 1229, 1086, 1013, 980, 826, 765, 645; GCMS (m=z) ¼ 318

CHALCONE-BASED N-FORMYL-PYRAZOLINES
697
[Mþ., C19H18Cl2N2O], 320, 291, 191, 179, 153, 138 (100%), 222, 209, 206, 194, 153,
145, 77, 69, 51.
5-(4-Bromophenyl)-3-phenyl-4,5-dihydropyrazole-1-carbaldehyde (2d).
1
Yield: 94%; white solid; mp: 104–106 ꢁC; H NMR (CDCl3, 500 MHz) d (ppm):
8.95 (s, 1H), 7.77–7.71 (m, 2H), 7.54–7.29 (m, 5H), 7.18–7.12 (m, 2H), 5.50 (dd,
J ¼ 5.0, 12.5 Hz, 1H), 3.82 (dd, J ¼ 11.9, 18.0 Hz, 1H), 3.20 (dd, J ¼ 5.0, 16.0 Hz,
1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 160.0, 155.6, 139.6, 132.2, 130.8,
130.7 (2C), 128.9 (2C), 127.5 (2C), 126.7 (2C), 124.9, 60.5, 42.4. IR vmax(KBr,
cmꢀ1): 1669, 1598, 1423, 1322, 1134, 1071, 1017, 831, 756, 690, 536, 442. GCMS
(m=z) ¼ 328 [Mþ., C16H13BrN2O], 330, 329, 327, 299, 250, 222, 153, 145, 145, 77, 51.
3-(4-Bromophenyl)-5-phenyl-4,5-dihydropyrazole-1-carbaldehyde (2e).
1
Yield: 93%; white solid; mp: 145–147 ꢁC; H NMR (CDCl3, 500 MHz) d (ppm):
8.95 (s, 1H), 7.59–7.50 (m, 4H), 7.45–7.35 (m, 1H), 7.29–7.23 (m, 4H), 5.54 (dd,
J ¼ 5.0, 17.0 Hz, 1H), 3.78 (dd, J ¼ 12.0, 13.0 Hz, 1H), 3.20 (dd, J ¼ 5.0, 17.5 Hz,
1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 159.9, 155.7, 139.5, 132.1, 130.6,
130.4 (2C), 128.8 (2C), 127.4 (2C), 126.2 (2C), 124.9, 60.4, 42.3; IR vmax (KBr,
cmꢀ1): 1668, 1598, 1413, 1322, 1134, 1071, 1017, 831, 756, 690, 536, 442; GCMS
(m=z) ¼ 328 [Mþ., C16H13BrN2O], 330, 329, 327, 299, 250, 222, 153, 145, 145, 77, 51.
3,5-Bis(4-bromophenyl)-4,5-dihydropyrazole-1-carbaldehyde (2f). Yield
92%; white solid; mp: 138–140 ꢁC; 1H NMR (CDCl3, 500 MHz) d (ppm): 8.93
(s, 1H), 7.86–7.84 (m, 2H), 7.58–7.54 (m, 2H), 7.45–7.36 (m, 2H), 7.28–7.19
(m, 2H), 5.53 (dd, J ¼ 5.0, 12.0 Hz, 1H), 3.79 (dd, J ¼ 12.5, 17.0 Hz, 1H), 3.19 (dd,
J ¼ 5.0, 16.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 160.2, 151.8, 131.9,
131.5, 131.2, 130.1, 128.2 (2C), 127.6 (2C), 125.9 (2C), 124.3 (2C), 60.0, 40.8; IR vmax
(KBr, cmꢀ1): 1649, 1611, 1511, 1430, 1362, 1324, 1225, 1129, 1076, 1017, 823, 735,
536; GCMS (m=z) ¼ 406 [Mþ., C16H12Br2N2O], 408, 407, 376, 328, 248, 221, 207,
154, 91, 77, 51.
3-(4-Bromophenyl)-5-p-tolyl-4,5-dihydropyrazole-1-carbaldehyde (2g).
1
Yield: 91%; white solid; mp: 180–182 ꢁC; H NMR (CDCl3, 500 MHz) d (ppm):
8.93 (s, 1H), 7.71–7.65 (m, 4H), 7.22–7.13 (m, 4H), 5.49 (dd, J ¼ 5.0, 11.0 Hz, 1H),
3.76 (dd, J ¼ 12.0, 17.5 Hz, 1H), 3.18 (dd, J ¼ 5.0, 16.5 Hz, 1H), 2.18 (s, 3H); 13C
NMR (CDCl3, 125 MHz) d (ppm): 160.0, 154.6, 137.8, 137.5, 132.0, 130.7, 129.9
(2C), 128.1 (2C), 125.6(2C), 125.0 (2C), 59.0, 42.5, 21.1; IR vmax(KBr, cmꢀ1): 1650,
1596, 1507, 1423, 1317, 1246, 1122, 1059, 1005, 819, 748, 553, 408; GCMS (m=
z) ¼ 342 [Mþ., C17H15BrN2O], 344, 343, 327, 313, 249, 243, 221, 145, 104, 77, 51, 15.
3(4-Bromophenyl)-5-(3,4-dimethoxyphenyl)-4,5-dihydropyrazole-1-
1
carbaldehyde (2h). Yield: 93%; white solid; mp: 118–120 ꢁC; H NMR (CDCl3,
500 MHz) d (ppm): 8.95 (s, 1H), 7.70–7.65 (m, 4H), 6.68–6.62 (m, 3H), 5.49 (dd,
J ¼ 4.5, 11.9 Hz, 1H), 3.82 (s, 6H), 3.74 (dd, J ¼ 11.0, 18.0 Hz, 1H), 3.18 (dd,
J ¼ 5.0, 17.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 160.2, 154.9, 153.6,
137.5, 136.3, 130.8, 128.9 (2C), 126.7 (2C), 125.3, 124.0, 123.3, 123.1, 112.2, 60.9,
59.3, 40.9; IR vmax (KBr, cmꢀ1): 2942, 1659, 1590, 1514, 1421, 1311, 1248, 1165,
1069, 1020, 822, 755, 632, 586, 528; GCMS (m=z) ¼ 388 [Mþ., C18H17BrN2O3],
390, 389, 359, 357, 327, 309, 249, 221, 154, 119, 91, 77, 65, 51, 31.

698
N. AHMED AND D. DEV
3-(4-Bromophenyl)-5-(3,4,5-trimethoxyphenyl)-4,5-dihydropyrazole-1-
1
carbaldehyde (2i). Yield: 93%; white solid; mp: 175–177 ꢁC; H NMR (CDCl3,
500 MHz) d (ppm): 8.98 (s, 1H), 7.81–7.65 (m, 4H), 6.46 (s, 2H), 5.47 (dd, J ¼ 5.0,
13.0 Hz, 1H), 3.80 (s, 9H), 3.60 (dd, J ¼ 12.0, 17.0 Hz, 1H), 3.16 (dd, J ¼ 5.0,
16.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 160.0, 155.7, 153.5, 137.4,
136.2, 130.7 (2C), 128.8 (2C), 126.6 (2C), 125.0, 103.1 (2C), 60.8, 59.3, 56.2 (2C),
42.8; IR vmax (KBr, cmꢀ1): 2929, 1665, 1595, 1503, 1422, 1327, 1241, 1124, 1022,
835, 752, 648, 542; GCMS (m=z) ¼ 418 [Mþ., C19H19BrN2O4], 420, 419, 390, 389,
388, 359, 357, 327, 309, 249, 221, 154, 119, 91, 77, 65, 51, 31.
3-Phenyl-5-(3,4,5-trimethoxyphenyl)-4,5dihydropyrazole-1-carbaldehyde
(2j). Yield: 94%; white solid; mp: 145–146 ꢁC. 1H NMR (CDCl3, 500 MHz) d (ppm):
9.00 (s, 1H), 7.73 (dd, J ¼ 1.5, 6.5 Hz, 2H), 7.48–7.42 (m, 3H), 6.46 (s, 2H), 5.47 (dd,
J ¼ 5.0, 12.0 Hz, 1H), 3.83 (s, 9H), 3.80 (dd, J ¼ 5.0, 16.0 Hz, 1H), 3.23 (dd, J ¼ 5.0,
16.5 Hz, 1H). 13C NMR (CDCl3, 125 MHz) d (ppm): 160.2, 155.9, 153.7, 137.5,
136.3, 130.8 (2C), 128.9 (2C), 126.7 (2C), 125.1, 102.2 (2C), 60.9, 59.2, 56.1 (2C),
42.9; IR vmax (KBr, cmꢀ1): 1667, 1593, 1508, 1459, 1419, 1325, 1243, 1226, 1011,
827, 759, 693,644. GCMS (m=z) ¼ 340 [Mþ., C19H20N2O4], 339, 311, 237, 222, 209,
206, 194, 19, 153, 145, 77 (100%), 76,65, 61.
5-(4-Chlorophenyl)-3-(2-hydroxyphenyl)-4,5-dihydropyrazole-1-carbal-
dehyde (2k). Yield: 87%; yellow solid; mp: 185–187 ꢁC; 1H NMR (CDCl3,
500 MHz) d (ppm): 8.90 (s, 1H), 7.44–7.32 (m, 4H), 7.22–7.20 (m, 3H), 6.92
(m, 1H), 5.48 (dd, J ¼ 5.0, 12.0 Hz, 1H), 3.90 (dd, J ¼ 11.5, 17.0 Hz, 1H), 3.33 (dd,
J ¼ 5.0, 17.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 160.4, 153.0, 151.5,
140.8, 132.5, 132.3, 131.4, 128.9 (2C), 127.2 (2C), 127.1, 125.2, 112.2, 59.1, 41.9;
IR vmax (KBr, cmꢀ1): 3423, 1670, 1610, 1490, 1428, 1324, 1251, 1219, 1086, 1013,
990, 825, 765, 640, 557; GCMS (m=z) ¼ 300 [Mþ., C16H13ClN2O2], 302, 301, 283,
265, 271, 249, 221, 173, 97, 77, 51.
3-(4-Hydroxyphenyl)-5-phenyl-4,5-dihydropyrazole-1-carbaldehyde (2l).
1
Yield: 85%; white solid; mp: 128–130 ꢁC; H NMR (CDCl3, 500 MHz) d (ppm):
9.00 (s, 1H), 7.73–7.71 (m, 2H), 7.46–7.42 (m, 3H), 7.29–7.23 (m, 1H), 7.17–7.00
(m, 1H), 6.70–6.68 (m, 2H), 5.49 (dd, J ¼ 4.5, 12.0 Hz, 1H), 3.79 (dd, J ¼ 12.0,
17.0 Hz, 1H), 3.23 (dd, J ¼ 4.0, 16.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d
(ppm): 160.4, 154.2, 151.1, 131.5, 131.5, 130.1, 128.1 (2C), 127.3 (2C), 125.4 (2C),
123.5 (2C), 59.5, 40.1; IR vmax (KBr, cmꢀ1): 3443, 1660, 1596, 1490, 1428, 1324,
1251, 1219, 1086, 1013, 990, 825, 765, 640, 557; GCMS (m=z) ¼ 266 [Mþ.,
C16H14N2O2], 268, 267, 249, 221, 173, 97, 51.
5-(3-Hydroxyphenyl)-3-phenyl-4,5-dihydropyrazole-1-carbaldehyde (2 m).
1
Yield: 83%; white solid; mp: 176–178 ꢁC. H NMR (CDCl3, 500 MHz) d (ppm):
9.00 (s, 1H), 7.77–7.72 (m, 2H), 7.48–7.41 (m, 3H), 7.29–7.23 (m, 1H), 7.17 (m,
1H), 6.70–6.68 (m, 2H), 5.49 (dd, J ¼ 4.5, 11.5 Hz, 1H), 3.79 (dd, J ¼ 12.0, 17.2 Hz,
1H), 3.23 (dd, J ¼ 4.5, 16.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 159.4,
152.6, 151.1, 132.3, 130.5, 130.1, 127.8 (2C), 127.3 (2C), 124.4 (2C), 122.5 (2C),
59.3, 40.8; IR vmax (KBr, cmꢀ1): 3443, 1660, 1596, 1490, 1428, 1324, 1251, 1219,
1086, 1013, 990, 825, 765, 640, 557; GCMS (m=z) ¼ 266 [Mþ., C16H14N2O2]; 268,
267, 249, 221, 173, 97, 51.

CHALCONE-BASED N-FORMYL-PYRAZOLINES
699
3-(2-Hydroxyphenyl)-5-(4-nitrophenyl)-4,5-dihydropyrazole-1-carbal-
dehyde (2n). Yield: 85%; white solid; mp: 178–180 ꢁC; 1H NMR (CDCl3,
500 MHz) d (ppm): 8.95 (s, 1H), 7.76–7.67 (m, 2H), 7.41–7.35 (m, 3H), 7.34–7.25
(m, 3H), 5.53 (dd, J ¼ 5.0, 11.0 Hz, 1H), 3.75 (dd, J ¼ 12.0, 17.0 Hz, 1H), 3.20 (dd,
J ¼ 4.5, 16.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 160.3, 153.2, 151.2,
140.7, 133.5, 132.2, 131.1, 128.5 (2C), 128.1 (2C), 127.1, 125.5, 113.4, 59.1, 41.9;
IR vmax (KBr, cmꢀ1): 3440, 1667, 1588, 1490, 1428, 1324, 1251, 1219, 1086, 1013,
990, 835, 746, 640, 557; GCMS (m=z) ¼ 311 [Mþ., C16H13N3O4]; 313, 312, 265,
249, 221, 219, 144, 97, 77, 51, 45.
3-(4-Chlorophenyl)-5-(3-nitrophenyl)-4,5-dihydropyrazole-1-carbaldehyde
(2o). Yield: 81%; white solid; mp: 139–141 ꢁC; 1H NMR (CDCl3, 500 MHz) d
(ppm): 8.96 (s, 1H), 8.21–8.18 (m, 2H), 7.67–7.58 (m, 3H), 7.35–7.22 (m, 3H), 5.65
(dd, J ¼ 5.0, 11.5 Hz, 1H), 3.89 (dd, J ¼ 12.0, 16.0 Hz, 1H), 3.21 (dd, J ¼ 5.0,
16.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 160.4, 140.1, 139.3, 132.3,
131.4, 130.1, 128.9 (2C), 127.3 (2C), 125.1, 124.1, 123.8, 116.4, 59.3, 41.1; IR vmax
(KBr, cmꢀ1): 1636, 1594, 1528, 1420, 1351, 1092, 823, 760, 686, 477; GCMS
(m=z) ¼ 329 [Mþ., C16H12ClN3O3], 331, 330, 294, 249, 221, 144, 97, 77, 51, 29.
Synthesis of Pyrazoloisoindole
General procedure. Six to eight drops of TFA were added to a well-stirred
and refluxed solution of N-formyl-pyrazoline (1.0 mmol) in acetonitrile (10 mL),
and the reaction was continued for 10–20 h. After TLC monitoring, the reaction mix-
ture was cooled, and the solvent was evaporated under reduced pressure. The residue
was dissolved in dichloromethane and 10% aqueous Na2CO3. After extraction, the
organic layer was dried on anhydrous Na2SO4 and evaporated under reduced press-
ure. The product was purified by silica-gel column chromatography in a mixture of
hexane and ethyl acetate (9:1 v=v) as eluent.
2-Phenyl-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one (3a). Yield: 94%;
white crystaline solid; mp: 108–110 ꢁC; 1H NMR (CDCl3, 500 MHz) d (ppm):
7.72–7.70 (m, 2H), 7.41–7.36 (m, 3H), 7.29–7.22 (m, 2H), 7.18–7.16 (m, 2H), 5.54
(dd, J ¼ 4.5, 11.5 Hz, 1H), 3.73 (dd, J ¼ 11.5, 17.5 Hz, 1H), 3.19 (dd, J ¼ 4.5,
17.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 156.8, 138.4, 131.0 130.3,
129.0, 128.1 (2C), 127.8 (2C), 127.3, 126.1 (2C), 124.5 (2C), 60.3, 40.7; IR vmax
(KBr, cmꢀ1): 1692, 1471, 1401, 1233, 1183, 1028, 943, 823, 750. GCMS (m=
z) ¼ 248 [Mþ., C16H12N2O], 241, 221, 215, 206, 205, 204, 178, 165, 146, 132, 115,
104, 103, 102; HR-MS (m=z) for C16H12N2O calcd. 248.0950; found: 248.0946.
6-Chloro-2-phenyl-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one (3b). Yield:
1
90%; white solid; mp: 145–147 ꢁC; H NMR (CDCl3, 500 MHz) d (ppm): 7.71 (d,
J ¼ 8.0 Hz, 2H), 7.42–7.38 (m, 3H), 7.24 (d, J ¼ 6.5 Hz, 1H), 7.12 (d, J ¼ 6.5 Hz,
2H), 5.50 (dd, J ¼ 4.5, 11.5 Hz, 1H), 3.73 (dd, J ¼ 11.5, 17.5 Hz, 1H), 3.16 (dd,
J ¼ 4.5, 17.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 156.2, 136.4, 132.7,
129.9, 128.4, 127.8 (2C), 127.3 (2C), 125.6 (2C), 125.6 (2C), 123.5, 59.2, 40.0; IR vmax
(KBr, cmꢀ1): 2924, 1703, 1560, 1469, 1403, 1275, 1221, 1196, 1170, 1144, 1084, 1009,

700
N. AHMED AND D. DEV
947, 843, 760, 698; GCMS (m=z) ¼ 282 [Mþ., C16H11ClN2O], 284, 283, 271, 206,
191,104, 102; HR-MS (m=z) for C16H11ClN2O calcd. 282.0560; found: 282.0546.
6-Chloro-2-(4-chlorophenyl)-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one
(3c). Yield: 93%; white solid; mp: 146–148 ꢁC; 1H NMR (CDCl3, 500 MHz) d
(ppm): 7.72–7.69 (m, 2H), 7.43–7.41 (m, 2H), 7.33–7.30 (m, 2H), 7.18–7.16
(m, 1H), 5.52 (dd, J ¼ 5.0, 11.5 Hz, 1H), 3.78 (dd, J ¼ 11.5, 17.5 Hz, 1H), 3.20 (dd,
J ¼ 5.0, 17.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 156.4, 135.4, 132.7,
129.0, 127.8 (2C), 127.4 (2C), 125.6, 125.6, 124.6, 123.9, 122.1, 118.0, 60.1, 41.0;
IR vmax(KBr, cmꢀ1): 1706, 1567, 1464, 1410, 1270, 1221, 1196, 1160, 1154, 1084,
1014, 943, 863, 763, 686; GCMS (m=z) ¼ 316 [Mþ., C16H10Cl2N2O], 318, 317, 281,
247, 171, 104, 102; HR-MS (m=z) for C16H10Cl2N2O calcd. 316.0170; found:
316.0181.
6-Bromo-2-phenyl-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one (3d). Yield:
89%; light pink solid; mp: 162–164 ꢁC; 1H NMR (CDCl3, 500 MHz) d (ppm):
7.76–7.69 (m, 2H), 7.55–7.45 (m, 2H), 7.45–7.28 (m, 2H), 7.10–7.04
(m, 2H), 5.49 (dd, J ¼ 5.0, 11.5 Hz, 1H), 3.72 (dd, J ¼ 5.0, 17.5 Hz, 1H), 3.15
(dd, J ¼ 4.5, 16.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 156.3, 137.5,
130.6, 130.3, 128.3, 127.6 (2C), 127.0 (2C), 125.1, 124.2, 123.9, 122.5, 116.2, 59.8,
40.0, IR vmax (KBr, cmꢀ1): 1691, 1463, 1401, 1282, 1199, 1159, 1070, 1010, 943,
826, 732, 657, 543. GCMS (m=z) ¼ 326 [Mþ., C16H11BrN2O], 328, 327, 247, 249,
171, 102; HR-MS (m=z) for C16H11BrN2O calcd. 326.0055; found: 326.0145.
2-(4-Bromophenyl)-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one (3e). Yield:
1
90%; white solid; mp: 146–148 ꢁC; H NMR (CDCl3, 500 MHz) d (ppm): 7.76–7.69
(m, 2H), 7.56–7.49 (m, 3H), 7.43–7.40 (m, 3H), 5.65 (dd, J ¼ 4.5, 11.5 Hz, 1H), 3.76
(dd, J ¼ 12.0, 17.5 Hz, 1H), 3.23 (dd J ¼ 4.5, 17.5 Hz, 1H); 13C NMR (CDCl3,
125 MHz) d (ppm): 156.8, 137.2, 130.1, 130.0, 128.4, 127.4 (2C), 127.3 (2C), 125.3,
124.1, 123.4, 122.5, 117.1, 60.5, 41.0; IR vmax (KBr, cmꢀ1): 1697, 1586, 1468,
1391, 1215, 1178, 1071, 1013, 943, 832, 752, 698, 658, 538. GCMS (m=z) ¼ 326
[Mþ. C16H11BrN2O], 328, 327, 247, 249, 171, 102; HR-MS (m=z) for C16H11BrN2O
calcd. 326.0055; found: 326.0154.
6-Bromo-2-(4-bromophenyl)-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one
(3f). Yield: 89%; white solid; mp: 138–140 ꢁC; 1H NMR (CDCl3, 500 MHz) d (ppm):
7.79 (dd, J ¼ 5.5, 8.0 Hz, 2H), 7.48 (d, J ¼ 8.0 Hz, 2H), 7.15–7.11 (m, 3H), 5.55 (dd,
J ¼ 4.5, 11.5 Hz, 1H), 3.80 (dd, J ¼ 11.5, 17.0 Hz, 1H), 3.20 (dd J ¼ 4.5, 16 Hz, 1H);
13C NMR (CDCl3, 125 MHz) d (ppm): 156.2, 136.9, 133.2, 129.1, 128.5 (2C), 126.9
(2C), 125.5, 125.4, 124.5, 124.0, 122.0, 119.1, 59.2, 40.1; IR vmax (KBr, cmꢀ1): 1702,
1598, 1452, 1403, 1341, 1219, 1161, 1017, 951, 839, 735, 594, 545; GCMS (m=z) ¼ 404
[Mþ., C16H10 Br2N2O], 407, 405, 403, 324, 247, 171, 104, 102. HR-MS (m=z) for
C16H11BrN2O calcd. 403.9160; found: 403.9154.
2-(4-Bromophenyl)-6-methyl-3,3a-dihydropyrazolo[5,1-a]isoindol-8-
one (3g). Yield: 87%; yellow solid; mp: 165–167 ꢁC; 1H NMR (CDCl3, 500 MHz) d
(ppm): 7.72–7.65 (m, 2H), 7.63–7.58 (m, 2H), 7.19–7.10 (m, 3H), 5.58 (dd, J ¼ 4.5,
11.0 Hz, 1H), 3.72 (dd, J ¼ 11.5, 16.5 Hz, 1H), 3.18 (dd, J ¼ 4.5, 16.0 Hz, 1H), 2.34
(s, 3H); 13C NMR (CDCl3, 125 MHz) d (ppm): 156.3, 136.2, 130.6, 130.3, 128.2,

CHALCONE-BASED N-FORMYL-PYRAZOLINES
701
127.5 (2C), 127.0 (2C), 126.2, 125.3, 124.2, 124.2, 123.7, 59.8, 40.0, 28.1; IR vmax
(KBr, cmꢀ1): 1698, 1596, 1507, 1413, 1318, 1256, 1112, 1049, 1005, 819, 748, 543;
GCMS (m=z) ¼ 340 [Mþ., C17H13BrN2O], 342, 341, 324, 247, 171, 102; HR-MS
(m=z) for C17H13BrN2O calcd. 340.2110; found: 340.2117.
2-(4-Bromophenyl)-6,7-dimethoxy-3,3a-dihydropyrazolo[5,1-a]isoindol-8-
one (3h). Yield: 88%; yellow solid; mp: 142–144 ꢁC; 1H NMR (CDCl3, 500 MHz) d
(ppm): 7.57 (d, J ¼ 8.5 Hz, 2H), 7.51 (d, J ¼ 8.5 Hz, 2H), 6.75 (m, 2H), 5.49 (dd,
J ¼ 4.5, 11.0 Hz, 1H), 3.76 (m, 6H), 3.67 (dd, J ¼ 4.5, 16.5 Hz, 1H), 3.16 (dd,
J ¼ 4.5, 16.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 156.3, 147.8, 147.5,
130.6 (2C), 130.3, 127.6, 127.0 (2C), 124.2, 116.2, 115.7, 113.5, 110.0, 59.6, 54.3
(2C), 40.0; IR vmax(KBr, cmꢀ1): 1695, 1598, 1519, 1461, 1409, 1253, 1221, 1193,
1157, 1024, 810, 727. GCMS (m=z) ¼ 386 [Mþ., C18H15BrN2O3], 387, 307, 277,
247, 171, 102; HR-MS (m=z) for C18H15BrN2O3 calcd. 386.0266; found: 386.0255.
2-(4-Bromophenyl)-5,6,7-trimethoxy-3,3a-dihydropyrazolo[5,1-a]isoindol-8-
one (3i). Yield: 87%; yellowish solid; mp: 188–190 ꢁC; 1H NMR (CDCl3, 500 MHz)
d (ppm): 7.65 (dd, J ¼ 1.5, 6.5 Hz, 2H), 7.59–7.57 (m, 2H), 6.40 (s, 1H), 5.56 (dd,
J ¼ 4.5, 11.5 Hz, 1H), 3.80 (s, 9H), 3.79 (dd, J ¼ 11.5, 18.0 Hz, 1H), 3.23 (dd,
J ¼ 4.5, 18.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 158.0, 147.7, 137.9,
135.0, 132.2, 129.1, 128.6 (2C), 127.5 (2C), 125.9, 117.3, 116.1, 115.2, 60.7, 57.8,
56.1 (2C), 41.8; IR vmax(KBr, cmꢀ1): 1695, 1592, 1503, 1464, 1418, 1337, 1224,
1164, 1126, 1067, 1001, 837, 701, 636, 536; GCMS (m=z) ¼ 416 [Mþ.,
C19H17BrN2O4], 418, 417, 385, 355, 337, 324, 247, 171; HR-MS (m=z) for
C19H17BrN2O4 calcd. 416.0372; found: 416.0364.
5,6,7-Trimethoxy-2-phenyl-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one
(3j). Yield: 90%; white solid; mp: 175–178 ꢁC; 1H NMR (CDCl3, 500 MHz) d (ppm):
7.80 (d, J ¼ 6.5 Hz, 2H), 7.47 (dd, J ¼ 7.0, 12.5 Hz, 3H), 6.42 (d, J ¼ 3.0 Hz, 1H), 5.57
(dd, J ¼ 4.5, 11.5 Hz, 1H), 3.82 ꢀ 3.79 (3 s, 9H), 3.49 (dd, J ¼ 11.5, 16.5 Hz, 1H), 3.27
(dd, J ¼ 4.5, 16.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 158.4, 146.8, 132.5,
131.5, 131.4, 128.9 (2C), 127.2 (2C), 126.5, 125.4, 118.6, 117.4, 116.7, 61.6, 60.5, 56.4
(2C), 41.9; IR vmax (KBr, cmꢀ1): 1702, 1594, 1510, 1462, 1421, 1342, 1163, 1130,
1002, 893, 831, 771, 631, 537 631, 537. GCMS (m=z) ¼ 338 [Mþ., C19H18N2O4],
340, 339, 311, 236 (100%), 222, 209, 206, 194, 153, 145, 77, 69, 51; HR-MS (m=z)
for C19H18N2O4 calcd. 338.1267; found 338.1271.
6-Chloro-2-(2-hydroxyphenyl)-3,3a-dihydropyrazolo[5,1-a]isoindol-8-
one (3k). Yield: 78%; yellow solid; mp: 157–159 ꢁC; 1H NMR (CDCl3, 500 MHz) d
(ppm): 7.34–7.33 (m, 2H), 7.24–7.18 (m, 3H), 7.10 ꢀ 6.97 (m, 1H), 6.97 ꢀ 6.94
(m, 1H), 5.57 (dd, J ¼ 4.5, 11.5 Hz, 1H), 3.94 (dd, J ¼ 12.0, 17.5 Hz, 1H), 3.38 (dd,
J ¼ 4.0, 17.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 156.8, 141.1, 132.3,
130.4, 130.2, 127.9 (2C), 126.8 (2C), 125.4, 124.3, 123.1, 120.5, 119.4, 60.3, 40.8;
IR vmax (KBr, cmꢀ1): 3431, 1694, 1606, 1470, 1407, 1304, 1225, 1073, 1013, 910,
814, 764, 503; GCMS (m=z) ¼ 298 [Mþ., C16H11ClN2O2], 300, 299, 281, 263, 247,
171, 77; HR-MS (m=z) for C16H11ClN2O2 calcd. 298.0509; found: 298.0510.
2-(4-Hydroxyphenyl)-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one (3l). Yield:
76%; white solid; mp: 126–128 ꢁC; 1H NMR (CDCl3, 500 MHz) d (ppm):

702
N. AHMED AND D. DEV
7.60–7.59 (m, 2H), 7.29–7.27 (m, 2H), 7.22 (d, J ¼ 7.5 Hz, 1H), 7.18–7.16 (m, 2H),
6.80–6.78 (m, 1H), 5.52 (br, D2O-exchangeble, 1H), 5.52 (dd, J ¼ 4.5, 11.5 Hz,
1H), 3.26 (dd, J ¼ 11.5, 17.5 Hz, 1H), 3.15(dd, J ¼ 4.5, 17.0 Hz, 1H); 13CNMR
(CDCl3, 125 MHz) d (ppm): 156.3, 141.1, 131.3, 130.4, 130.2, 128.8 (2C), 127.2
(2C), 125.3, 123.0, 117.3, 115.4, 112.9, 60.6, 40.1; IR vmax (KBr, cmꢀ1): 3349,
1669, 1600, 1490, 1451, 1358, 1271, 1222, 1169, 1038, 939, 841, 773, 615, 541, 470.
GCMS (m=z) ¼ 264 [Mþ., C16H12N2O2], 266, 265, 247, 171, 102, 77, 55; HR-MS
(m=z) for C16H12N2O2 calcd. 264.0899; found: 264.0889.
7-Hydroxy-2-phenyl-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one (3m). Yield:
75%; white solid; mp: 148–150 ꢁC; 1H NMR (CDCl3, 500 MHz) d (ppm):
7.78–7.72 (m, 2H), 7.50–7.42 (m, 3H), 6.77–6.67 (m, 3H), 5.55 (br,
D2O-exchangeble, 1H), 5.53 (dd, J ¼ 4.5, 12.0 Hz, 1H), 3.78 (dd, J ¼ 11.5,
17.5 Hz, 1H), 3.26 (dd, J ¼ 4.5, 17.0 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d
(ppm): 156.4, 141.1, 131.4, 130.5, 130.1, 128.9 (2C), 127.3 (2C), 125.3, 123.1,
117.4, 115.5, 112.7, 61.3, 41.8; IR vmax (KBr, cmꢀ1): 3457, 1679, 1604, 1588,
1402, 1353, 1217, 1158, 760, 695. GCMS (m=z) ¼ 264 [Mþ., C16H12N2O2], 266,
265, 247, 171, 102, 77, 55; HR-MS (m=z) for C16H12N2O2 calcd. 264.0899; found:
264.0898.
2-(2-Hydroxyphenyl)-6-nitro-3,3a-dihydropyrazolo[5,1-a]isoindol-8-one
(3n). Yield: 74%; white solid; mp: 156–158 ꢁC; 1H NMR (CDCl3, 500 MHz) d
(ppm): 7.64 (dd, J ¼ 1.5, 7.0 Hz, 2H), 7.62–7.33 (m, 2H), 7.29–7.27 (m, 1H), 7.22
(m, 2H), 5.55 (dd, J ¼ 4.5, 11.5 Hz, 1H), 3.70 (dd, J ¼ 11.5, 17.5 Hz, 1H), 3.15 (dd
J ¼ 4.5, 17.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 156.4, 143.8, 137.5,
132.3, 131.4, 128.9, 127.2 (2C), 126.8, 125.2, 123.8, 122.1, 121.3, 119.0, 60.8, 41.9;
IR vmax (KBr, cmꢀ1): 3443, 1696, 1584, 1480, 1418, 1334, 1246, 1215, 1086, 1014,
986, 845, 746, 641, 558; GCMS (m=z) ¼ 309 [Mþ.,C16H11N3O2], 311, 310, 292, 247,
171, 102, 77, 55; HR-MS (m=z) for C16H11N3O2 calcd. 309.0750; found: 309.0744.
2-(4-Chlorophenyl)-7-nitro-3,3a-dihydropyrazolo[5,1-a]isoindol-8-
1
one (3o). Yield: 75%; white solid; mp: 180–182 ꢁC; H NMR (CDCl3, 500 MHz) d
(ppm): 8.21–8.19 (m, 1H), 7.73 (d, J ¼ 8.5 Hz, 2H), 7.58–7.55 (m, 2H), 7.46 (d,
J ¼ 9.0 Hz, 2H), 5.58 (dd, J ¼ 5.0, 12.0 Hz, 1H), 3.92 (dd, J ¼ 11.5, 17.5 Hz, 1H),
3.23 (dd, J ¼ 4.5, 17.5 Hz, 1H); 13C NMR (CDCl3, 125 MHz) d (ppm): 156.4,
141.1, 142.3, 132.4, 130.5, 130.1, 128.9, 127.3 (2C), 126.5 (2C), 125.1, 124.3, 117.4,
60.3, 40.1; IR vmax (KBr, cmꢀ1): 1701, 1594, 1538, 1425, 1355, 1087, 833, 766,
714, 676, 524 467; GCMS (m=z) ¼ 327 [Mþ., C16H10ClN3O3]; 329, 328, 292, 291,
171, 77, 55; HR-MS (m=z) for C16H10ClN3O3 calcd. 327.0411; found: 327.0412.
ACKNOWLEDGMENTS
This work was financially supported by the Indian Institute of Technology
Roorkee through Ministry of Human Resource Development (MHRD), New Delhi.
D. D. thanks MHRD for the award of fellowship.

CHALCONE-BASED N-FORMYL-PYRAZOLINES
703
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