Synthesis and antitumour activity of a novel class of flavanones: 1,4-diaryl-1,4-dihydrochromeno[4,3-c]pyrazoles

Article abstract of DOI:10.3184/174751912X13263828746643

A new series of 1,4-diaryl-1,4-dihydrochromeno[4,3-c]pyrazoles have been synthesised. The target compounds and their analogues (2,4-diaryl-2,4- dihydrochromeno[4,3-c]pyrazoles) were tested for their antitumour activities in vitro against MCF-7 and HL-60 c

Full text of DOI:10.3184/174751912X13263828746643

JOURNAL OF CHEMICAL RESEARCH 2012
RESEARCH PAPER 45
JANUARY, 45–48
Synthesis and antitumour activity of a novel class of flavanones:
1,4-diaryl-1,4-dihydrochromeno[4,3-c]pyrazoles
Zhiwei Chen, Zhihua Wang and Weike Su*
Key Laboratory of Pharmaceutical Engineering of Ministry of Education, College of Pharmaceutical Sciences, Zhejiang University of
Technology, Hangzhou 310014, P. R. China
A new series of 1,4-diaryl-1,4-dihydrochromeno[4,3-c]pyrazoles have been synthesised. The target compounds
and their analogues (2,4-diaryl-2,4-dihydrochromeno[4,3-c]pyrazoles) were tested for their antitumour activities
in vitro against MCF-7 and HL-60 cells using the MTT method. Among these compounds, 1,4-bis(4-chlorophenyl)-
1,4-dihydrochromeno[4,3-c]pyrazole was found to have potent antitumour activity in vitro with minimum IC50 of
25.31 µg mL−1 and 13.86 µg mL−1 against MCF-7 and HL-60 cells respectively.
Keywords: flavonoids, pyrazoles, antitumour activity, Vilsmeier reagent
Flavanones are an important class of heterocyclic compounds
found in many synthetic and natural products. They possess a
wide variety of pharmacological activities, such as antiviral,1
antitumour,2 antibacterial,3 anti-HIV,4 antioxidant and anti-
inflammatory5 properties. Some of the flavanones displayed
enhanced bioactivity after structural modification. Thus flava-
nones containing a 1,2,3-thiadiazoline ring have been found to
have effective antiproliferative activity in vivo.6
Previously, we reported a new method for the preparation
of 2,4-diaryl- 2,4-dihydrochromeno[4,3-c]pyrazoles 5 from
flavanone-4- arylhydrazones utilising a Vilsmeier reagent.7
As the extension of our previous work, we describe their
analogues: 1,4-diaryl-1,4-dihydrochromeno[4,3-c]pyrazoles 4
(Scheme 1). We have evaluated their antitumour activities
in vitro against MCF-7 and HL-60 cells.
In order to optimise the reaction conditions, the reaction of
2-p-tolylchroman-4-one 1a and BTC/DMF was chosen as a
model reaction. We first examined the influence of the ratio of
1a/BTC/DMF using ClCH2CH2Cl as solvent. It was found that
a molar ratio 1:1:3 of 1a/BTC/DMF was suitable. If the ratio
was decreased, the yield was reduced dramatically. Then the
effect of temperature on the reaction was studied. The reaction
of compound 1a with Vilsmeier reagent (BTC/DMF) was
first attempted at room temperature for 5 h but it provided the
product 2a in low yield (60%), and the starting material 1a
was not completely consumed as indicated by TLC. When
we treated of 1a with BTC/DMF at 60 °C for 3 h, the reaction
proceeded smoothly in 85% yield. Subsequently, solvent
screening was performed by means of the reaction of 1a with
BTC/DMF under these conditions. Several conventional
organic solvents such as CH2Cl2, CH3CN, DMF were tested,
and DMF was found to be more suitable due to its excellent
dissolving power, and the yield of 2a increased to 90%.
Our initial investigation into the synthesis of 1-phenyl-4-p-
tolyl-1,4-dihydrochr-omeno[4,3-c]pyrazole 4a used the reaction
of the corresponding 4-chloro-2-p-tolyl-2H-chromene-3-
carbaldehyde 2a and commercially available phenylhydrazine
hydrochloride in refluxing EtOH in the presence of triethyl-
amine. Unfortunately, the desired product 4a was not obtained.
Instead, the intermediate 1-[(4-chloro-2-p-tolyl-2H-chromen-
3-yl)methylene]-2-phenylhydrazine 3a was obtained in good
yield (92%). Numerous reagents (pyridine, AcONa, DABCO
and K2CO3), temperature and solvents (THF, CH3CN DMF
and AcOH) were employed, but none furnished the cyclic
product 4a. To our delight, the target compound 4a was
obtained in 48% yield from corresponding 3a by refluxing in
DMF in the presence of NaH under an atmosphere of N2.
The subsequent study was performed under the optimal con-
ditions described above. Most of the products, 1,4-diaryl-1,4-
dihydrochromeno[4,3-c]pyrazoles, were obtained in 30–40%
yields (overall yields based on flavanones 1). Their structures
were confirmed by IR, 1H NMR, 13C NMR, MS and HRMS.
The compounds 4a–k and 5a–i were screened for their
antiproliferative activity in vitro against two tumour cell lines
including the human breast cancer cell line MCF-7 and the
human leukaemia cell line HL-60. The antitumour drug,
cisplatin, was used together as a positive control in the assays.
The results are summarised in Table 1. Some general conclu-
sions can be drawn from the experiment.
Results and discussion
β-Chlorovinylaldehydes are important synthons in the synthe-
sis of many natural products. An earlier report8 showed that
4-chloro-2-aryl-2H- chromene-3-carbaldehydes can be easily
synthesised in good yields by corresponding treatment of the
flavanones treated with the Vilsmeier reagent (prepared from
POCl3 and DMF).8 However, this reaction employs the toxic
reagent POCl3 which is harmful to human health and is
an environmental pollutant. Recently, we have shown that
bis-(trichloromethyl)carbonate (BTC, triphosgene) can be
employed as a mild, highly efficient and environmentally
benign reagent for the preparation of a novel Vilsmeier reagent
in place of POCl3 and COCl2.9−11 We provide here an improved
method for the preparation of 4-chloro-2-aryl-2H-chromene-
3-carbaldehydes 2 from the corresponding flavanones 1 using
a Vilsmeier reagent derived from BTC and DMF as shown in
Scheme 2. The flavanones 1 were easily prepared by the previ-
ously reported methods in good yields from commercially
available arylketones and arylaldehydes.12
(1) Cytotoxicity assay demonstrated that most of compounds
4 were potentially efficient antitumour compounds against the
HL-60 cell, and displayed more effective activity than 5 in this
test.
(2) The compound 4e exhibited potent antiproliferative
activity against both the MCF-7 and HL-60 cells with IC50
values of 25.31 µg mL−1 and 13.86 µg mL−1 respectively.
Scheme 1
* Correspondent. E-mail: pharmlab@zjut.edu.cn

46 JOURNAL OF CHEMICAL RESEARCH 2012
Scheme 2
Scheme 3
Table 1 In vitro cytotoxic activity of 1,4-diaryl-1,4-dihydro-
chromeno[4,3-c]pyr-azoles4a–kand2,4-diaryl-2,4-dihydrochro-
meno[4,3-c]pyrazoles 5a–i
(3) The compounds 4a, 4c, 4d, 4e, 4f and 4j showed high
activity against the HL-60 cell but low activity against the
MCF-7 cell. Among them, 4a and 4d displayed more effective
activity against the HL-60 cell than cisplatin.
In conclusion, a new series of 1,4-diaryl-1,4-dihydrochro-
meno[4,3-c]pyrazoles have been synthesised from correspond-
ing flavanones by a novel and efficient method. Then we
studied the antitumour activities in vitro of the target com-
pounds and their analogues (2,4-diaryl-2,4-dihydrochromeno
[4,3-c]pyrazoles). Most of the compound 4 displayed more
effective activity than 5 in this test. In particular, 4e showed
potent activity against both the HL-60 and MCF-7 cells, whilst
4a and 4d displayed more effective activity against the HL-60
cell than cisplatin.
Entry
R1
R2
R3
Com-
pounds
IC50: µg mL−1
MCF-7 HL-60
1
2
3
4
5
6
H
H
H
H
H
H
4-CH3
4-CH3
H
4-Cl
4-Cl
4-Cl
H
4-Cl
H
4a
4b
4c
4d
4e
4f
>50
>50
>50
>50
13.23
>50
19.43
12.14
13.86
27.37
H
4-Cl
4-OCH3
25.31
>50
7
8
H
5-CH3
5-CH3
5-CH3
5-CH3
H
4-OCH3
H
H
H
4-Cl
H
4-Cl
H
4-Cl
4-OCH3
H
4g
4h
4i
>50
>50
36.84
46.81
33.60
29.04
9
H
>50
10
11
12
13
14
15
16
4-Cl
4-Cl
4-Cl
4-Cl
4-Cl
4-OCH3
4j
>50
Experimental
4k
5a
5b
5c
5d
5e
>50
>50
All reagents were purchased from commercial suppliers and were
used without further purification. Melting points were measured on a
Büchi B-540 capillary melting point apparatus and are uncorrected.
The NMR spectra were measured with aVarian 400 (400 MHz) instru-
ment using CDCl3 as the solvent with TMS as internal standard. IR
spectra were recorded using KBr pellets on a Nicolet Aviatar-370
instrument. Mass spectra were measured with Thermo Finnigan LCQ-
Advantage. High resolution mass spectral (HRMS) analysis was mea-
sured on an Agilent 6210 TOF LC/MS using ESI or EI (electrospray
ionisation) techniques. The tumour cell lines (Bel-72 and HL-60)
were obtained from Shanghai Institutes for Biological Sciences.
Cisplatin was the product of Qilu Pharmaceutical Co., Ltd.
>50
>50
>50
>100
>100
>100
H
>50
H
>100
>100
>100
H
H
4-OCH3 4-OCH3
17
18
19
20
21
H
3,4-CH3
H
H
H
5f
5g
5h
5i
>100
>100
>100
>100
>100
>100
>100
>100
5-CH3
5-CH3 4-OCH3 4-OCH3
5-CH3
4-Cl
H
Cisplatin
16.52
13.37
Synthesis of 4-chloro-2-p-tolyl-2H-chromene-3-carbaldehyde (2a);
general procedure
BTC (0.59 g, 2 mmol) was slowly added to DMF (3 mL) at 0 ºC, the
mixture was stirred at room temperature for 30 min, then 2-p-tolyl-
chroman-4-one 1a (2 mmol) was added, the reaction mixture was kept
at 60 °C for 2 h. After completion of the reaction, the reaction mixture
was poured into 10 mL of ice-water, neutralised with saturated
NaHCO3 solution and extracted with dichloromethane (15 mL× 3).
The combined organic phases were washed with water, brine, dried

JOURNAL OF CHEMICAL RESEARCH 2012 47
over Na2SO4, evaporated. The product were recrystallised from meth-
anol to give yellow crystals 2a in 90% yield.
13C NMR (100 MHz, CDCl3): δ = 153.4, 140.3, 139.6, 136.1, 133.7,
129.8, 129.4 (CH×2), 129.0, 128.9, 128.8 (CH×2), 127.7 (CH×2),
126.2 (CH×2), 122.6, 121.5, 118.2, 118.0, 115.9, 77.0; MS (ESI): m/z
= 325.3 (M++1). HRMS-ESI: m/z (M++1) Calcd for C22H17N2O:
325.1341; found: 325.1345.
4-Chloro-2-p-tolyl-2H-chromene-3-carbaldehyde (2a):Yellow solid;
m.p. 97–98 °C (lit.8 98 °C); IR (KBr): νmax = 2860, 1667, 1601,
1294 cm−1; 1H NMR (400 MHz, CDCl3): δ = 10.27 (s, 1H), 7.71 (dd,
J1 = 8.0 Hz, J2 = 1.6 Hz, 1H), 7.32–7.28 (m, 1H), 7.18 (d, J = 8.0 Hz,
2H), 7.06 (d, J = 8.0 Hz, 2H), 7.02–6.98 (m, 1H), 6.86 (d, J = 8.0 Hz,
1H), 6.36 (s, 1H) 2.28 (s, 3H). 13C NMR (100 MHz, CDCl3):
δ = 187.8, 154.9, 143.4, 138.5, 135.0, 134.2, 129.1 (CH×2), 126.8,
126.7 (CH×2), 126.3, 121.7, 119.9, 117.3, 75.0, 21.2.; MS (EI): m/z
(%) = 284 (25), 255 (100).
4-(4-Chlorophenyl)-1-phenyl-1,4-dihydrochromeno[4,3-c]pyrazole
(4d): Overall yield: 39%; yellow solid; m.p. 113–115 °C; IR (KBr):
1
νmax = 2924, 1555, 1446, 754 cm−1; H NMR (400 MHz, CDCl3):
δ = 7.51-7.50 (m, 5H), 7.45–7.36 (m, 4H), 7.29 (s, 1H), 7.16–7.12 (m,
1H), 7.00 (d, J = 8.0 Hz, 1H), 6.85–6.83 (m, 1H), 6.76–6.72 (m, 1H),
6.35 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 152.9, 140.0, 137.9,
135.6, 134.4, 133.5, 129.6, 129.2 (CH×2), 128.8 (CH×2), 128.7
(CH×2), 125.9 (CH×2), 122.4, 121.4, 117.9, 117.2, 115.5, 76.2; MS
(ESI): m/z (%) = 359.4 (M++1, 100), 361.3(M++3, 35). HRMS-ESI:
m/z (M++1) Calcd for C22H16ClN2O: 359.0951; found: 359.0955.
1,4-Bis(4-chlorophenyl)-1,4-dihydrochromeno[4,3-c]pyrazole(4e):
Synthesis of 1-[(4-chloro-2-p-tolyl-2H-chromen-3-yl)-methylene]-2-
phenylhydrazine (3a); general procedure
A solution of 2a (1 mmol), phenylhydrazine hydrochloride (2 mmol)
and triethylamine (2 mmol) in anhydrous ethanol (10 mL) was refluxed
for 5 h. After completion of the reaction, the mixture was then cooled
to room temperature and evaporated under reduced pressure, poured
into 20 mL of water and extracted with dichloromethane (15 mL× 3).
The combined organic phases were washed with water, brine, dried
over Na2SO4, and concentrated under vacuum, the crude product was
further purified using column chromatography (silica gel, petroleum
ether: EtOAc = 30:1, v/v) to give 3a in 92% yield.
1-[(4-Chloro-2-p-tolyl-2H-chromen-3-yl)methylene]-2-phenylhy-
drazine (3a): Yellow solid; m.p. 159–161 °C; IR (KBr): νmax = 3312,
1598, 1545, 1258 cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.86 (s, 1H),
7.73 (s, 1H), 7.53–7.51 (m, 1H), 7.28 (s, 1H), 7.21–7.17 (m, 2H),
7.13–7.10 (m, 1H), 7.02 (d, J = 8.0 Hz, 2H), 6.93–6.78 (m, 6H),
6.56 (s, 1H), 2.23(s, 3H); 13C NMR (100 MHz, CDCl3): δ = 152.8,
143.4, 138.0, 135.7, 132.7, 130.4, 129.1 (CH×2), 128.9 (CH×2), 127.1
(CH×2), 126.5, 125.8, 124.4, 121.6, 121.3, 120.6, 116.7, 112.8
(CH×2), 76.6, 21.2; MS (ESI): m/z (%) = 397.1 (M++Na, 100), 399.1
(M++Na+2, 30). HRMS-ESI: m/z (M++1), Calcd for C22H18ClN2O:
375.1264; found: 375.1273.
Overall yield: 38%; yellow solid; m.p. 161–162 °C; IR (KBr): νmax
=
3085, 1493, 1453, 838 cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.50–
7.45 (m, 4H), 7.43–7.35 (m, 4H), 7.29 (s, 1H), 7.18–7.14 (m, 1H),
7.00 (d, J = 8.4 Hz, 1H), 6.88–6.86 (m, 1H), 6.78 (t, J = 7.6 Hz, 1H),
6.33 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 152.9, 138.5, 137.8,
136.0, 134.6, 134.5, 133.6, 129.9 (CH×2), 129.4 (CH×2), 128.8
(CH×2), 127.1 (CH×2), 122.3, 121.5, 118.1, 117.7, 115.3, 76.1; MS
(ESI): m/z (%) = 393.4 (M++1, 100), 395.4(M++3, 66). HRMS-ESI:
m/z (M++1) Calcd for C22H15Cl2N2O: 393.0561; found: 393.0564.
4-(4-chlorophenyl)-1-(4-methoxyphenyl)-1,4-dihydrochromeno[4,3-c]
pyrazole (4f): Overall yield: 34%; yellow solid; m.p. 195–197 °C; IR
1
(KBr): νmax = 2960, 1526, 1248, 838 cm−1; H NMR (400 MHz,
CDCl3): δ = 7.45–7.40 (m, 4H), 7.38 (s, 1H), 7.35 (s, 1H), 7.26 (s,
1H), 7.17–7.10 (m, 1H), 7.02–6.98 (m, 3H), 6.83–6.81 (m, 1H), 6.76–
6.72 (m, 1H), 6.35 (s, 1H), 3.89 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ = 159.7, 152.9, 138.0, 135.3, 134.4, 133.5, 133.0, 129.5, 128.8
(CH×2), 128.7 (CH×2), 127.3 (CH×2), 122.3, 121.4, 117.8, 116.6,
115.6, 114.4 (CH×2), 76.2, 55.6; MS (ESI): m/z (%) = 389.2 (M++1,
100), 391.2 (M++3, 29). HRMS-ESI: m/z (M++1) Calcd for
C23H18ClN2O2: 389.1057; found: 389.1063.
Synthesis of 1-phenyl-4-p-tolyl-1,4-dihydrochromeno- [4,3-c]pyrazole
(4a); general procedure
4-(4-Methoxyphenyl)-1-phenyl-1,4-dihydrochromeno[4,3-c]pyrazole
(4g): Overall yield: 30%; yellow solid; m.p. 166–168 °C; IR (KBr):
A 25-mL two-necked flask was equipped with a stir bar, condenser,
and placed under a nitrogen atmosphere. Into the flask was placed 3a
(3 mmol) and 3 mmol of a 60% mineral oil dispersion of NaH. Dry
DMF (10 mL) was added, the mixture was stirred for 10 min at room
temperature and then refluxed for 5 h. The mixture was then cooled
to room temperature and poured into 20 mL of water, and extracted
with dichloromethane (15 mL× 3). The combined organic phases
were washed with water, brine, dried over Na2SO4, evaporated, and
the crude product was purified by chromatography on silica gel
(petroleum ether: EtOAc = 40:1, v/v) to give 4a in 48% yield.
1-Phenyl-4-p-tolyl-1,4-dihydrochromeno[4,3-c]pyrazole (4a): Over-
all yield: 40%; yellow solid; m.p. 108–109 °C; IR (KBr): νmax = 2863,
1453, 1211, 760 cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.56–7.45 (m,
5H), 7.40 (d, J = 8.0 Hz, 2H), 7.30 (s, 1H), 7.22 (d, J = 8.0 Hz, 2H),
7.15–7.11 (m, 1H), 7.01–6.99 (m, 1H), 6.86–6.84 (m, 1H), 6.76–6.70
(m, 1H), 6.34 (s, 1H), 2.38 (s, 3H); 13C NMR (100 MHz, CDCl3):
13C NMR (100 MHz, CDCl3): δ = 153.5, 140.6, 138.3, 137.0, 136.0,
133.7, 129.5, 129.4, 129.2 (CH×4), 128.7, 127.4 (CH×2), 126.2
(CH×2), 122.4, 121.1, 118.0, 115.8, 77.0, 21.2. MS (ESI): m/z = 339.3
(M++1). HRMS-ESI: m/z (M++1) Calcd for C23H19N2O: 339.1497;
found: 339.1498.
1
νmax = 2958, 1514, 1454, 1247 cm−1; H NMR (400 MHz, CDCl3):
δ = 7.57–7.41 (m, 7H), 7.29 (s, 1H), 7.16–7.09 (m, 1H), 7.00–6.98 (m,
1H), 6.95–6.90 (m, 2H), 6.86–6.83 (m, 1H), 6.75–6.71 (m, 1H), 6.32
(s, 1H), 3.82 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 159.8, 153.2,
140.1, 135.9, 133.6, 131.4, 129.5, 129.2 (CH×2), 129.1 (CH×2),
128.7, 125.9, 122.4, 121.2, 117.9 (CH×2), 115.6, 113.9 (CH×2), 76.8,
55.3; MS (ESI): m/z = 355.2 (M++1). HRMS-ESI: m/z (M++1) Calcd
for C23H19N2O2: 355.1447; found: 355.1446.
8-Methyl-1,4-diphenyl-1,4-dihydrochromeno[4,3-c]pyrazole (4h):
Overall yield: 39%; yellow solid; m.p. 122–124 °C; IR (KBr): νmax
=
2923, 1468, 1221, 767 cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.55–
7.50 (m, 7H), 7.40–7.36 (m, 3H), 7.29 (s, 1H), 6.96–6.90 (m, 2H),
6.64 (s, 1H), 6.32 (s, 1H), 2.07 (s, 3H); 13C NMR (100 MHz, CDCl3):
δ = 151.1, 140.2, 139.5, 135.8, 133.7, 130.4, 130.1, 129.1 (CH×2),
128.7, 128.5 (CH×4), 127.4 (CH×2), 125.9, 122.9, 117.9, 117.6,
115.4, 76.8, 20.8; MS (ESI): m/z = 339.2 (M++1). HRMS-ESI: m/z
(M++1) Calcd for C23H19N2O: 339.1497; found: 339.1498.
1-(4-Chlorophenyl)-8-methyl-4-phenyl-1,4-dihydrochromeno[4,3-c]
pyrazole (4i): Overall yield: 31%; yellow solid; m.p. 131–133 °C;
1
IR (KBr): νmax = 2922, 1494, 1212, 834 cm−1; H NMR (400 MHz,
1-(4-Chlorophenyl)-4-p-tolyl-1,4-dihydrochromeno[4,3-c]pyrazole
(4b): Overall yield: 31%; yellow solid; m.p. 148–150 °C; IR (KBr):
CDCl3): δ = 7.51–7.46 (m, 6H), 7.42–7.34 (m, 3H), 7.29 (s, 1H),
6.98–6.97 (m, 1H), 6.93–6.91 (m, 1H) 6.69 (s, 1H), 6.29 (s, 1H), 2.12
(s, 3H); 13C NMR (100 MHz, CDCl3): δ = 151.4, 139.6, 139.0, 136.6,
134.7, 134.1, 131.0, 130.7, 129.6 (CH×2), 128.9, 128.8 (CH×2), 127.7
(CH×2), 127.3 (CH×2), 123.0, 118.7, 118.2, 115.5, 77.1, 21.2; MS
(ESI): m/z (%) = 373.1 (M++1, 100), 375.1 (M++3, 33). HRMS-ESI:
m/z (M++1) Calcd for C23H18ClN2O: 373.1108; found: 373.1106.
4-(4-Chlorophenyl)-8-methyl-1-phenyl-1,4-dihydrochromeno[4,3-c]
pyrazole (4j): Overall yield: 34%; yellow solid; m.p. 136–138 °C;
1
νmax = 2923, 1493, 1455, 752 cm−1; H NMR (400 MHz, CDCl3):
δ = 7.48 (s, 4H), 7.38 (d, J = 8.0 Hz, 2H), 7.29 (s, 1H), 7.22 (s, 1H),
7.20 (s, 1H), 7.18–7.11 (m, 1H), 7.02–7.00 (m, 1H), 6.88–6.86 (m,
1H), 6.79–6.75 (m, 1H), 6.31 (s, 1H), 2.37 (s, 3H); 13C NMR (100
MHz, CDCl3): δ = 153.4, 138.9, 138.5, 136.5, 136.3, 134.5, 133.7,
129.7, 129.4 (CH×2), 129.2 (CH×2), 127.4 (CH×2), 127.2 (CH×2),
122.3, 121.2, 118.3, 118.1, 115.5, 76.9, 29.8; MS (ESI): m/z (%) =
373.2 (M++1, 100), 375.2 (M++3, 33). HRMS-ESI: m/z (M++1) Calcd
for C23H18ClN2O: 373.1108; found: 373.1109.
1
IR (KBr): νmax = 2921, 1521, 1471, 763 cm−1; H NMR (400 MHz,
CDCl3): δ = 7.51–7.49 (m, 5H), 7.43–7.41 (m, 2H), 7.36–7.34 (m,
2H), 7.28 (s, 1H), 6.95–6.88 (m, 2H), 6.62 (s, 1H), 6.29 (s, 1H), 2.06
(s, 3H); 13C NMR (100 MHz, CDCl3): δ = 150.7, 139.9, 137.9, 135.6,
134.3, 133.6, 130.6, 130.1, 129.1 (CH×2), 128.8 (CH×2), 128.6
(CH×2), 125.8 (CH×2), 122.9, 117.6, 117.4, 115.2, 76.0, 20.9; MS
1,4-Diphenyl-1,4-dihydrochromeno-[4,3-c]pyrazole (4c): Overall
yield: 37%; yellow solid. m.p. 110–111 °C; IR (KBr): νmax = 3066,
1
1511, 1496, 1212 cm−1; H NMR (400 MHz, CDCl3): δ = 7.55–7.48
(m, 7H), 7.43–7.37 (m, 3H), 7.30 (s, 1H), 7.17–7.10 (m, 1H), 7.03–
7.01 (m, 1H), 6.86–6.84 (m, 1H), 6.76–6.72 (m, 1H), 6.38 (s, 1H);

48 JOURNAL OF CHEMICAL RESEARCH 2012
(ESI): m/z (%) = 373.2 (M++1, 100), 375.2 (M++3, 32). HRMS-ESI:
m/z (M++1) Calcd for C23H18ClN2O: 373.1108; found: 373.1101.
1,4-Bis(4-chlorophenyl)-8-methyl-1,4-dihydrochromeno[4,3-c]
pyrazole (4k): Overall yield: 39%; yellow solid; m.p. 176–178 °C; IR
(KBr): νmax = 2920, 1492, 1216, 839 cm-1; 1H NMR (400 MHz, CDCl3):
δ = 7.48 (s, 4H), 7.42-7.34 (m, 4H), 7.28 (s, 1H), 6.98–6.96 (m, 1H),
6.91–6.89 (m, 1H), 6.68 (d, J = 1.2 Hz, 1H), 6.27 (s, 1H), 2.11 (s, 3H);
13C NMR (100 MHz, CDCl3): δ = 150.7, 138.5, 137.7, 136.0, 134.4,
133.7, 130.9, 130.4, 129.3 (CH×2), 128.7 (CH×2), 128.7 (CH×2),
126.9 (CH×2), 122.7, 117.9, 117.8, 115.1, 76.0, 21.0; MS (ESI): m/z
(%) = 407.2 (M++1, 100), 409.2 (M++3, 44). HRMS-ESI: m/z (M++1)
Calcd for C23H17Cl2N2O: 407.0718; found: 407.0718.
Received 13 December 2011; accepted 7 January 2012
Paper 1101037 doi: 10.3184/174751912X13263828746643
Published online: 31 January 2012
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