New Vilsmeier reaction for facile synthesis of 4-phenyl-2,4- dihydrochromeno[4,3-c]pyrazoles with Bis(trichloromethyl) carbonate/DMF

Article abstract of DOI:10.3184/030823410X12888867039388

An efficient method for the synthesis of 4-phenyl-2,4-dihydrochromeno[4,3- c]pyrazoles via the cyclisation reaction of the easily available flavanone-4-arylhydrazones with Vilsmeier reagent (Bis(trichloromethyl) carbonate/DMF) has been developed.

Full text of DOI:10.3184/030823410X12888867039388

JOURNAL OF CHEMICAL RESEARCH 2010
RESEARCH PAPER 661
NOVEMBER, 661–664
New Vilsmeier reaction for facile synthesis of 4-phenyl-2,4-
dihydrochromeno[4,3-c]pyrazoles with bis(trichloromethyl)
carbonate/DMF
Zhiwei Chen, Yanyan Yang 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
An efficient method for the synthesis of 4-phenyl-2,4- dihydrochromeno[4,3-c]pyrazoles via the cyclisation reaction
of the easily available flavanone-4-arylhydrazones with Vilsmeier reagent (Bis(trichloromethyl) carbonate /DMF) has
been developed.
Keywords: Vilsmeier reagent, pyrazoles, flavanone, cyclisation
Flavonoids are a class of plant secondary metabolites which
exhibit a wide range of pharmacological activities,1 including
anti-inflammatory,2 anti-viral3 and anti-cancer4 properties. The
broad biological roles and versatile activities of the flavonoids
have led to intensive research into their pharmacology and
chemistry.5,6 Moreover, experiments have shown that most of
the flavonoids would display an enhanced biological activity
after structural modification such as the introduction of hetero-
cyclic rings.7,8 For example, Hu and his group designed
and synthesised a series of new flavonoids with a 1,2,3-
thiadiazoline ring which exhibited in vivo inhibitory effect on
tumor growth.9
was made to develop a suitable ratio of substrates and BTC/
DMF using DMF as solvent. After screening a variety of ratios
(Table 1), a ratio 1:2/3:2 ratio of 3a/BTC/DMF was determined
to be suitable. Solvents such as DMF, ClCH2CH2Cl, CH2Cl2,
CH3CN, and chlorobenzene (Table 1, entries 2, 6–9) were also
tested. DMF was found to give maximum yield followed by
chlorobenzene. Variations in the temperature of the reaction
were also explored in DMF, and 60 °C was found to be
sufficient to carry out the conversion.
The subsequent study was performed under the optimised
conditions as described above. Most of the corresponding
products, substituted 4-phenyl-2,4-dihydrochromeno[4,3-c]
pyrazoles 4, were obtained in moderate yields when R3 = H,
as show in Table 2. It was observed that the process clearly
tolerated different substituents R1, and R2.
According to the experimental results, it was found that the
reaction yields were affected strongly by different substituents
R3. When R3 = Cl, a considerable decrease in yield (only 20%
yield) took place while the temperature was kept at 60 °C for
4 h. Increasing the reaction temperature changed the yield
evidently to 54–60% while the temperature was elevated to
75 °C for 6 hours (Table 2, entries 9–11). Furthermore, when
R3 = 4-MeO, Treatment of 3 with BTC/DMF at 60 °C for 4 h
gave no product. The detection of the considerable amount of
flavanones 1 in the reaction mixture (monitored by TLC) indi-
cated that hydrolysis of hydrazones 3 had taken place due to
their thermal instability at higher temperature. However, when
this reaction was proceeded in 5–10 °C for 4 h, product 4 was
obtained in satisfactory yields (Table 2, entries 12–15). As
noticed, strong electron-donating groups in the arylhydrazines
make the formation of corresponding products easier. It
might be because a higher electron density of nitrogen atom
(Ar-NH-) led to enhanced nucleophilicity to promote the
cyclisation step.
The pyrazole ring is one of the basic fragments in medicinal
chemistry.10–13 We aimed to synthesise a mini library of novel
flavonoids containing a pyrazole ring. Earlier reports from
Kumar’s group showed that dihydroquinolone hydrazones,
after treatment with the Vilsmeier reagent (prepared from
POCl3 and DMF) formed 4,5-dihydropyrazolo-[4,3-c]
quinolines in a reasonable yield. This led us to apply a similar
method to the synthesis of 4-phenyl-2,4-dihydrochromeno
[4,3-c]pyrazoles which have a structural similarity to Kumar’s
products.14 However, the traditional Vilsmeier reagent employs
toxic reagents such as POCl3 which form phosphorus salts,
that are harmful to human health and hazardous to the environ-
ment.15 As part of our interest in developing the cyclisation
potential of the Vilsmeier reagent16 and reducing environmen-
tal pollution, we now report an efficient and green method for
the preparation of 4-phenyl-2,4-dihydrochromeno[4,3-c]
pyrazoles. In this reaction, bis-(trichloromethyl)carbonate
(BTC) was employed as a mild, highly efficient and environ-
mentally benign reagent for the preparation of the Vilsmeier
reagent. 4-Phenyl-2,4-dihydrochromeno[4,3-c]pyrazoles were
synthesised with the hope that they might have efficient antitu-
mor activity and low toxicity through modification of ring C.
Most substituted flavanones 1, which were prepared
following Bu’s procedure,17 were treated with a substituted
phenylhydrazine in ethanol at reflux to form a variety of
flavanone-4-arylhydrazones. Unfortunately, flavanone-4-
arylhydrazones with R3 = p-MeO could not be prepared under
these conditions. However this product could be obtained by
stirring 1 and (4-methoxyphenyl)hydrazine in ethanol under
the protection of N2 at room temperature using acetic acid
as catalyst. The flavanone-4-arylhydrazones 3 which were
prepared were subsequently treated with the Vilsmeier reagent
(BTC/DMF) under an atmosphere of N2. A series of substi-
tuted 4-phenyl-2,4-dihydrochromeno[4,3-c]pyrazoles 4 were
synthesised smoothly, as shown in Scheme 1.
Bearing in mind the acylation activity of Vilsmeier reagents,
the process might also give formylation products 5. Disap-
pointingly, no corresponding products were observed even
when a ratio 1:10/3:10 ratio of 3a/BTC/DMF was used. This
might be due to the steric hindrance of the groups on the
pyrazole ring. A plausible mechanism for this cyclisation
reaction is proposed in Scheme 2.
In conclusion, a mild and efficient method for the prepara-
tion of 2-substituted-4-phenyl-2,4-dihydrochromeno[4,3-c]
pyrazoles starting from corresponding flavanones has been
developed. The simplicity, easy work-up and adaptation to
a wide range of substrates made it useful in the synthesis of
flavonoid derivatives.
To validate our protocol, initially, the reaction of compound
3a with Vilsmeier reagent (BTC/DMF) was chosen as model
reaction to investigate different conditions. Considerable effort
Experimental
Melting points were measured on a Büchi B-540 capillary melting
point apparatus. The NMR spectra were measured with a Varian
400 (400 MHz) instrument using CDCl3 as the solvent with TMS as
* Correspondent. E-mail: pharmlab@zjut.edu.cn

662 JOURNAL OF CHEMICAL RESEARCH 2010
Scheme 1
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 measured on an Agilent 6210 TOF LC/MS
using APCI (electrospray ionisation) techniques.
7.27–7.22 (m , 2H), 7.06 (t, J = 7.2 Hz, 1H), 7.01 (d, J = 8.4 Hz, 1H),
6.36 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 154.2, 144.9, 140.2,
140.1, 129.7, 129.4, 129.1 (CH×2), 128.7 (CH×2), 127.4 (CH×2),
126.4, 123.1, 122.7, 122.0, 119.0 (CH×2), 118.5, 117.8, 117.5, 76.2;
MS (ESI): m/z = 325.3 (M++1). HRMS-ESI: m/z (M++1) Calcd for
C22H17N2O: 325.1341. Found: 325.1355.
Preparation of 4-phenyl-2,4-dihydro -chromeno[4,3-c]pyrazoles (4a);
general procedure
4-(3,4-dimethylphenyl)-2-phenyl-2,4-dihydrochromeno[4,3-c]
pyrazole (4b): White solid; m.p. 204–206°C; IR (KBr): νmax= 2921,
DMF (2 mL) was placed in a 25 mL three-necked flask, and BTC
(0.18 g, 0.6 mmol) was added in batch at 0 °C, then the mixture was
stirred at room temperature for 30 min to form the Vilsmeier salt. The
1-phenyl-2-(2-phenylchroman-4-ylidene)hydrazine 3a (0.9 mmol)
was added. The mixture was stirred at room temperature for 30 min-
utes, and then on an oil bath kept at 60 °C for 4 h. After completion of
the reaction, monitored by TLC (petroleum ether : ethyl acetate = 5:1),
the mixture was diluted with ice water, neutralised with saturated
NaHCO3 solution and extracted with dichloromethane (10 mL× 3).
The combined organic phases were washed with water, brine, dried
over Na2SO4. The solvent was evaporated and the crude product was
purified by on silica gel (petroleum ether: EtOAc = 20:1) to give 4a.
2,4-diphenyl-2,4-dihydrochromeno[4,3-c]pyrazole (4a): White
solid; m.p. 202−203 °C; IR (KBr): νmax = 2915, 1600, 1505, 1228 cm−1;
1H NMR (400 MHz, CDCl3): δ = 7.93 (dd, J1 = 7.2 Hz, J2 = 1.6 Hz,
1H), 7.67 (d, J = 7.6 Hz, 2H), 7.53–7.51 (m, 2H), 7.45–7.38 (m, 6H),
1
1600, 1503, 1245 cm−1; H NMR (400 MHz, CDCl3): δ = 7.90 (d,
J = 7.6 Hz, 1H), 7.66 (d, J = 8.4 Hz, 2H), 7.44–7.38 (m, 3H), 7.27–
7.16 (m, 5H), 7.03 (t, J = 7.6 Hz, 1H), 6.97 (d, J = 8.0 Hz, 1H), 6.28
(s, 1H), 2.27 (s, 6H); 13C NMR (100 MHz, CDCl3): δ = 154.1, 144.9,
139.9, 137.4, 137.3, 136.9, 129.8, 129.6, 129.2 (CH×2), 128.7, 126.2,
124.9, 123.1, 122.5, 121.7, 118.9 (CH×2), 118.6, 117.7, 117.4, 76.2,
20.0, 19.7; MS (EI): m/z (%) = 352 (M+, 100). HRMS-EI: m/z (M+)
Calcd for C24H20N2O: 352.1576. Found: 352.1588.
4-(4-methoxyphenyl)-2-phenyl-2,4-dihydrochromeno[4,3-c]
pyrazole (4c): White solid; m.p. 197−198 °C; IR (KBr): νmax= 2923,
1
1599, 1506, 1249 cm−1; H NMR (400 MHz, CDCl3): δ = 7.93 (d,
J = 7.2 Hz, 1H), 7.70 (d, J = 8.4 Hz, 2H), 7.47–7.42 (m, 5H), 7.29–
7.22 (m, 2H), 7.07–6.93 (m, 4H), 6.33 (s, 1H), 3.83 (s, 3H); 13C NMR
(100 MHz, CDCl3): δ = 160.4, 154.5, 145.5, 140.4, 132.6, 130.1,
129.7 (CH×2), 129.4 (CH×2), 126.7, 123.5, 123.0, 122.2, 119.3
(CH×2), 119.0, 118.1, 117.8, 114.4 (CH×2), 76.2, 55.7; MS (ESI):
m/z = 355.3 (M++1). HRMS-ESI: m/z (M++1) Calcd for C23H19N2O2:
355.1447. Found: 355.1459.
Table 1 Reaction of flavanone-4-arylhydrazones 3a with
DMF/BTC
4-(4-chlorophenyl)-2-phenyl-2,4-dihydrochromeno[4,3-c]pyrazole
(4d): white solid; m.p. 191−192 °C; IR (KBr): νmax = 2919, 1600,
Entry 3a:BTC:DMF Solvent
Conditions Yield /%a
1
1505, 1228 cm−1; H NMR (400 MHz, CDCl3): δ = 7.92 (dd, J1 =
7.6 Hz, J2 = 1.6 Hz, 1H), 7.69 (d, J = 7.6 Hz, 2H), 7.46–7.37 (m, 7H),
7.30–7.23 (m, 2H), 7.07 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 8.4 Hz, 1H),
6.35 (s, 1H); 13C NMR (100 MHz, CDCl3): δ = 153.9, 144.9, 139.9,
138.7, 134.6, 129.9, 129.5 (CH×2), 128.9 (CH×2), 128.8 (CH×2),
126.6, 123.1, 122.7, 122.2, 119.1, 118.0 (CH×2), 117.7, 117.5,
75.4; MS (ESI): m/z (%) = 359.2 (M++1, 100), 361.2 (M++3, 30).
HRMS-ESI: m/z (M++1) Calcd for C22H16ClN2O: 359.0951. Found:
359.0935.
1
2
3
4
5
6
7
8
9
1:1/3:1
1:2/3:2
1:1:3
1:2/3:2
1:2/3:2
1:2/3:2
1:2/3:2
1:2/3:2
1:2/3:2
DMF
60 °C, 4h
60 °C, 4h
60 °C, 4h
r.t., 4h
75 °C, 4h
60 °C, 6h
Reflux, 5h
45
62
61
42
60
52
51
54
48
DMF
DMF
DMF
DMF
ClCH2CH2Cl
CH2Cl2
Chlorobenzene 60 °C, 7h
CH3CN 60 °C, 4h
7-methyl-2,4-diphenyl-2,4-dihydrochromeno[4,3-c]pyrazole(4e):
White solid; m.p. 188−189 °C; IR (KBr): νmax = 2919, 1597, 1504,
a Isolated yields based on 3a.

JOURNAL OF CHEMICAL RESEARCH 2010 663
Table 2 preparation of 4-phenyl-2,4-dihydrochromeno[4,3-c]pyrazoles
Entry
R1
R2
R3
Product
Conditionsa
Yield /%b
1
2
H
H
H
4a
4b
4c
4d
4e
4f
4g
4h
4i
4j
4k
4l
4m
4n
4o
60 °C,4 h
60 °C,4 h
60 °C,4 h
60 °C,4 h
60 °C,4 h
60 °C,4 h
60 °C,4 h
60 °C,4 h
75 °C,6 h
75 °C,6 h
75 °C,6 h
5 °C,2 h
62
65
63
60
64
61
62
65
60
56
54
64
62
62
58
H
3,4-(CH3)2
4-OCH3
4-Cl
H
3
H
H
5-CH3
5-CH3
5-CH3
5-CH3
H
5-CH3
H
H
H
H
4
H
5
H
4-Cl
H
6
H
7
3,4-(OCH3)2
4-OCH3
3,4-(CH3)2
4-OCH3
4-Cl
3,4-(CH3)2
4-OCH3
4-OCH3
3,4-(CH3)2
H
8
H
9
4-Cl
4-Cl
4-Cl
4-OCH3
4-OCH3
4-OCH3
4-OCH3
10
11
12
13
14
15
5 °C,2 h
5-CH3
5-CH3
5 °C,2 h
5 °C,2 h
a Monitored by TLC, reaction ceased when 3 was fully consumed.
b Isolated yield by column chromatography.
Scheme 2
1
1245 cm−1; H NMR (400 MHz, CDCl3): δ = 7.83 (d, J = 7.6 Hz, 1H),
126.5, 123.1, 123.0, 122.5, 119.0 (CH×2), 117.9, 117.7, 114.9, 75.4,
21.6; MS (ESI): m/z (%) = 373.3 (M++1, 100), 375.2 (M++3, 33).
HRMS-ESI: m/z (M++1) Calcd for C23H18ClN2O: 373.1108. Found:
373.1093.
7.69 (d, J = 8.0 Hz , 2H), 7.52 (dd, J1 = 8.0 Hz, J2 = 1.6 Hz, 2H),
7.46–7.40 (m, 6H), 6.89 (d, J = 7.6 Hz, 1H), 6.84 (s, 1H), 6.36 (s, 1H),
2.34 (s, 3H) ; 13C NMR (100 MHz, CDCl3): δ = 154.1, 145.1, 140.2,
140.1, 129.4 (CH×2), 128.7 (CH×2), 127.4 (CH×2), 126.4, 123.1,
122.9, 122.5, 119.0, 118.2 (CH×2), 117.9, 114.9, 76.2, 21.60. MS
(ESI): m/z = 339.4 (M++1). HRMS-ESI: m/z (M++1) Calcd for
C23H19N2O: 339.1497. Found: 339.1507.
4-(3,4-dimethoxyphenyl)-8-methyl-2-phenyl-2,4-dihydrochromeno
[4,3-c]pyrazole(4g): White solid; m.p. 193–194 °C; IR (KBr):
1
νmax = 2941, 1639, 1598, 1511, 1275 cm−1; H NMR (400 MHz,
CDCl3): δ = 7.76 (s, 1H), 7.69 (d, J = 8.0 Hz, 2H), 7.45–7.41 (m, 3H),
7.28–7.25 (m, 1H), 7.08–7.03 (m, 3H), 6.90 (dd, J1 = 8.0 Hz, J2 =
11.6 Hz, 2H), 6.25 (s, 1H), 3.90 (s, 3H), 3.86 (s, 3H), 2.36 (s, 3H);
13C NMR (100 MHz, CDCl3): δ = 152.1, 149.5, 149.2, 145.4, 140.0,
132.5, 131.4, 130.4, 129.4 (CH×2), 126.4, 123.2, 122.9, 122.4, 120.2,
118.9 (CH×2), 117.5, 117.2, 110.8, 110.6, 76.2, 55.9 (CH×2), 20.7;
MS (ESI): m/z = 399.3 (M++1). HRMS-ESI: m/z (M++1) Calcd for
C25H23N2O3: 399.1709. Found: 399.1720.
4-(4-chlorophenyl)-7-methyl-2-phenyl-2,4-dihydrochromeno[4,3-c]
pyrazole(4f): White solid; m.p. 180–181 °C; IR (KBr): νmax = 2905,
1598, 1504 , 1243 cm−1; H NMR (400 MHz, CDCl3): δ = 7.81 (d,
1
J = 7.6 Hz, 1H), 7.68 (d, J = 8.4 Hz, 2H), 7.46–7.37 (m, 7H), 7.28 (d,
J = 7.6 Hz, 1H), 6.89 (d, J = 7.6 Hz, 1H), 6.82 (s, 1H), 6.33 (s, 1H),
2.33 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 153.8, 145.1, 140.3,
140.0, 138.9, 134.6, 129.4 (CH×2), 128.9 (CH×2), 128.8 (CH×2),

664 JOURNAL OF CHEMICAL RESEARCH 2010
4-(4-methoxyphenyl)-7-methyl-2-phenyl-2,4-dihydrochromeno
2,4-bis(4-methoxyphenyl)-8-methyl-2,4-dihydrochromeno[4,3-c]
pyrazole (4n): White solid; m.p. 212–213 °C; IR (KBr): νmax = 2950,
1612, 1515, 1245 cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.74 (s, 1H),
7.59 (d, J = 8.8 Hz, 2H), 7.44 (d, J = 8.8 Hz, 2H), 7.36 (s, 1H), 7.02
(d, J = 8.4 Hz, 1H), 6.96-6.92 (m, 4H), 6.88 (d, J = 8.4 Hz, 1H), 6.27
(s, 1H), 3.83 (s, 3H), 3.82 (s, 3H) , 2.35 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ = 160.0, 158.2, 152.0, 144.9, 133.8, 132.4, 131.2, 130.2,
129.0 (CH× 2), 123.3, 122.8, 120.8 (CH×2), 118.4, 117.5, 117.2,
114.5 (CH×2), 114. 0 (CH×2), 75.8, 55.6, 55.3, 20.7; MS (ESI):
m/z = 399.3 (M++1). HRMS-ESI: m/z (M++1) Calcd for C25H23N2O3:
399.1709. Found: 399.1700.
[4,3-c]pyrazole(4h): White solid; m.p. 176−177 °C; IR (KBr):
1
νmax = 2915, 1623, 1598, 1502, 1256 cm−1; H NMR (400 MHz,
CDCl3): δ = 7.81 (d, J = 7.6 Hz, 1H), 7.68 (d, J = 7.6 Hz, 2H), 7.47 (s,
1H), 7.43 (t, J = 7.6 Hz, 2H), 7.33 (t, J = 7.6 Hz, 1H), 7.28–7.24 (m,
1H), 7.10–7.07 (m, 2H), 6.93–6.85 (m, 3H), 6.32 (s, 1H), 3.81 (s, 3H),
2.34 (s, 3H); 13C NMR (100 MHz, CDCl3): δ = 159.9, 154.1, 145.1,
141.9, 140.2, 140.1, 129.7, 129.4 (CH×2), 126.3, 123.1, 122.9, 122.5,
119.6, 119.0, 118.2 (CH×2), 118.0, 115.0, 114.3, 112.8, 76.1, 55.3,
21.6; MS (ESI): m/z = 369.3 (M++1). HRMS-ESI: m/z (M++1) Calcd
for C24H21N2O2: 369.1603. Found: 369.1611.
4-(3,4-dimethylphenyl)-2-(4-methoxyphenyl)-8-methyl-2,4-
2-(4-chlorophenyl)-4-(3,4-dimethylphenyl)-2,4-dihydrochromeno
[4,3-c]pyrazole(4i): White solid; m.p. 205–207 °C; IR (KBr):
νmax = 2919, 1614, 1595, 1498, 1261 cm−1; 1H NMR (400MHz, CDCl3):
δ = 7.99 (d, J = 7.6 Hz, 1H), 7.71 (d, J = 8.8 Hz, 2H), 7.50–7.46 (m,
3H), 7.37–7.27 (m, 4H), 7.14 (t, J = 7.6 Hz, 1H), 7.08 (d, J = 8.0 Hz,
1H), 6.36 (s, 1H), 2.37 (s, 6H); 13C NMR (100 MHz, CDCl3):
δ = 154.4, 145.4, 138.6, 137.5, 137.4, 137.1, 131.7, 130.0 (CH×2),
129.5 (CH×2), 128.8, 125.0, 123.1, 122.7, 121.9, 120.0 (CH×2),
119.1, 117.6, 117.5, 76.2, 19.9, 19.6; MS (ESI): m/z (%) = 387.4
(M++1, 60), 385.4 (M+-1, 100). HRMS-ESI: m/z (M++1) Calcd for
C24H20ClN2O: 387.1264. Found: 387.1249.
dihydrochromeno[4,3-c]pyrazole(4o): White solid; m.p. 213–215 °C;
1
IR (KBr): νmax = 2915, 1593, 1515, 1243 cm−1; H NMR (400 MHz,
CDCl3): δ = 7.73 (s, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.36 (s, 1H), 7.30–
7.23 (m, 2H), 7.17 (d, J = 7.6 Hz, 1H), 7.03 (d, J = 8.0 Hz, 1H), 6.95
(d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.0 Hz, 1H), 6.26 (s, 1H), 3.84 (s, 3H),
2.35 (s, 3H), 2.28( s, 6H); 13C NMR (100 MHz, CDCl3): δ = 158.1,
152.0, 137.7, 137.3, 137.0, 133.9, 131.2, 130.2, 129.9, 128.8, 125.0,
123.3, 122.7, 120.7 (CH×2), 118.4, 117.5, 117.2 (CH×2), 114.4
(CH×2), 76.1, 55.6, 20.7, 19.9, 19.6; MS (ESI): m/z = 397.3 (M++1).
HRMS-ESI: m/z (M++1) Calcd for C26H25N2O2: 397.1916. Found:
397.1897.
2-(4-chlorophenyl)-4-(4-methoxyphenyl)-8-methyl-2,4-dihydro-
chromeno[4,3-c]pyrazole(4j): White solid; m.p. 202–203 °C; IR
(KBr): νmax = 2905, 1612, 1597, 1498, 1249 cm−1; 1H NMR (400MHz,
CDCl3): δ = 7.73 (s, 1H), 7.63 (d, J = 8.8 Hz, 2H), 7.45–7.38 (m, 5H),
7.05 (d, J = 8.0 Hz, 1H), 6.94 (d, J = 8.8 Hz, 2H), 6.89 (d, J = 8.0 Hz,
1H), 6.25 (s, 1H), 3.83 (s, 3H), 2.36 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ = 160.0, 152.1, 145.7, 138.6, 132.1, 131.7, 131.3, 130.6,
129.4 (CH×2), 129.0 (CH×2), 123.0, 122.9, 119.9 (CH×2), 119.3,
117.3, 117.2, 114.1 (CH×2), 75.7, 55.3, 20.7; MS (ESI): m/z (%) =
403.3 (M++1, 100), 405.3 (M++3, 33), 401.3 (M+-1, 70). HRMS-ESI:
m/z (M++1) Calcd for C24H20ClN2O2: 403.1213. Found: 403.1193.
2,4-bis(4-chlorophenyl)-2,4-dihydrochromeno[4,3-c]pyrazole(4k):
White solid; m.p. 201–203 °C; IR (KBr): νmax = 2912, 1617, 1596,
1498, 1253 cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J = 7.6 Hz,
1H), 7.64 (d, J = 8.8 Hz, 2H), 7.46–7.38 (m, 7H), 7.28–7.24 (m, 1H),
7.08 (t, J = 7.6 Hz, 1H), 7.00 (d, J = 8.4 Hz, 1H), 6.34 (s, 1H ); 13C
NMR (100 MHz, CDCl3): δ = 153.9, 145.1, 138.5, 138.4, 134.7,
131.9, 130.1, 129.5 (CH×2), 129.0 (CH×2), 128.8 (CH×2), 122.9,
122.7, 122.2, 120.0 (CH×2), 118.4, 117.5, 117.4, 75.3; MS (ESI): m/z
(%) = 393.4 (M++1, 48), 359.1 (M++2-Cl, 100). HRMS-ESI: m/z
(M++1) Calcd for C22H15Cl2N2O: 393.0561. Found: 393.0571.
1-Phenyl-2-(2-phenylchroman-4-ylidene)hydrazine(3a): 1H NMR
(400 MHz, DMSO-d6): δ = 9.41 (s, 1H), 8.04 (d, J = 7.6 Hz, 1H), 7.55
(d, J = 7.2 Hz, 2H), 7.44–7.34 (m, 3H), 7.25–7.17 (m, 5H), 7.00 (t,
J = 8.0, 1H), 6.93 (d, J = 8.0 Hz, 1H), 6.74 (d, J = 6.8 Hz, 1H),
5.19 (dd, J1 = 2.8 Hz, J2 = 12.0 Hz, 1H), 3.38–3.32 (m, 1H), 2.70 (dd,
J1 = 12.0 Hz, J2 = 16.8 Hz, 1H); 13C NMR(100 MHz, DMSO-d6)
δ = 155.3, 145.5, 140.2, 135.0, 134.7, 128.7 (CH×2), 128.3 (CH×2),
128.0, 126.3 (CH×2), 123.3, 121.6, 121.3, 118.8, 117.2, 112.4 (CH×2),
76.4, 32.3.
Received 28 July 2010; accepted 29 September 2010
Paper 1000269 doi: 10.3184/030823410X12888867039388
Published online: 24 November 2010
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meno[4,3-c]pyrazole(4l): White solid; m.p. 203–205 °C; IR (KBr):
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νmax = 2914, 1614, 1511, 1249 cm−1; H NMR (400 MHz, CDCl3):
δ = 8.37 (s, 1H), 8.17 (d, J = 7.6 Hz, 1H), 7.37–6.89 (s, 10H), 5.13 (d,
J = 10.8 Hz, 1H), 3.81 (s, 3H), 2.27 (s, 6H); 13C NMR (100 MHz,
CDCl3): δ = 165.4, 158.4, 158.1, 155.7, 137.1, 136.9, 136.4, 133.4,
129.8 (CH×2), 127.5, 126.9, 126.2, 123.8 (CH×2), 122.4, 121.2,
118.4, 117.7, 114.5 (CH×2), 77.7, 55.6, 20.0, 19.7; MS (EI): m/z (%)
= 382 (M+, 40), 133 (100). HRMS-EI: m/z (M+) Calcd for C25H22N2O2:
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c]pyrazole(4m): White solid; m.p. 206–208 °C; IR (KBr): νmax = 2962,
1613, 1517, 1245 cm−1; 1H NMR (400 MHz, CDCl3): δ = 7.91 (d, J =
7.6 Hz, 1H), 7.59 (d, J = 8.8 Hz, 2H), 7.45 (d, J = 8.4 Hz, 2H), 7.37 (s,
1H), 7.22 (t, J = 7.6 Hz, 1H), 7.05 (t, J = 7.6 Hz, 1H), 6.99–6.93 (m,
5H), 6.32 (s, 1H), 3.84 (s, 3H), 3.83 (s, 3H); 13C NMR (100 MHz,
CDCl3): δ = 160.1, 158.3, 154.2, 144.8, 133.9, 132.5, 129.7, 129.2
(CH×2), 123.4, 122.6, 122.0, 120.8 (CH×2), 118.3, 118.1, 117.6,
114.6 (CH×2), 114.2 (CH×2), 76.1, 55.7, 55.4; MS (ESI): m/z = 385.3
(M++1). HRMS-ESI: m/z (M++1) Calcd for C24H21N2O3: 385.1552.
Found: 385.1548.
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