One-pot synthesis of 2H-phenanthro[9,10-c]pyrazoles from isoflavones by two dehydration processes

Article abstract of DOI:10.1039/c3gc40205c

An environmentally friendly and efficient method was developed for one-pot synthesis of a series of 2H-phenanthro[9,10-c]pyrazoles in EtOH by two dehydration processes. Firstly, 3,4-diaryl-1H-pyrazoles were synthesized by the cyclocondensation of isoflavones and hydrazine hydrate in refluxing EtOH. Secondly, the final target products 2H-phenanthro[9,10-c]pyrazoles were given by photocyclization and dehydration of 3,4-diaryl-1H-pyrazoles in 1=:=1 (v/v) EtOH-H₂O. The advantages of this method are catalyst-free, short synthetic routes, mild reaction conditions and easy work-up. In addition, the fluorescence properties of 2H-phenanthro[9,10-c]pyrazoles were determined.

Full text of DOI:10.1039/c3gc40205c

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One-pot synthesis of 2H-phenanthro[9,10-c]pyrazoles
from isoflavones by two dehydration processes†
Cite this: Green Chem., 2013, 15, 1048
Qiuya Wang,a,b Zunting Zhang,*a Zichao Du,a Huiliang Huaa and Shasha Chena
An environmentally friendly and efficient method was developed for one-pot synthesis of a series of
2H-phenanthro[9,10-c]pyrazoles in EtOH by two dehydration processes. Firstly, 3,4-diaryl-1H-pyrazoles
were synthesized by the cyclocondensation of isoflavones and hydrazine hydrate in refluxing EtOH. Sec-
ondly, the final target products 2H-phenanthro[9,10-c]pyrazoles were given by photocyclization and
dehydration of 3,4-diaryl-1H-pyrazoles in 1 : 1 (v/v) EtOH–H2O. The advantages of this method are cata-
lyst-free, short synthetic routes, mild reaction conditions and easy work-up. In addition, the fluorescence
properties of 2H-phenanthro[9,10-c]pyrazoles were determined.
Received 25th January 2013,
Accepted 10th February 2013
DOI: 10.1039/c3gc40205c
www.rsc.org/greenchem
Introduction
Pyrazole and its derivatives, although scarcely found in nature,
constitute an interesting family of heterocycles due to their
wide applications. For instance, they are shown to possess
important biological and pharmaceutical activities1 such as
anti-inflammatory,2 antipyretic,3 antitumor,4 gastric secretion
stimulatory,5 anti-depressant,6 antibacterial,7 antifilarial
agents,8 anti-obesity,9 estrogen receptor agonist,10 HIV-1
reverse transcriptase inhibitors11 and anti-hyperglycemic
activities.12 They are also useful intermediates for industrial
products.13 In addition, pyrazole derivatives are also used as
insecticides, herbicides and fungicides.14 Due to promising
pharmacological and agrochemical applications, 3,4-diaryl-
pyrazoles are being used as inhibitors of heat-shock protein 90
(HSP90) and as therapeutics of cancer.15 Syntheses of 3,4-di-
arylpyrazoles have been reported over the past decades.16 Iso-
flavone, as one kind of nature product, shows remarkable
biological anticancer and cardiovascular protection, etc.17 We
have synthesized 3,4-diaryl-1H-pyrazoles by a one-pot pro-
cedure based on the reaction of natural isoflavones with hydra-
zine hydrate.18
Scheme 1 The retrosynthetic analysis of 2H-phenanthro[9,10-c]pyrazoles.
derivatives, we planned the synthesis of 2H-phenanthro[9,10-c]-
pyrazoles 1 by cyclization of the corresponding 3,4-diaryl-1H-
pyrazoles 2 (Scheme 1). Although many syntheses of pyrazoles
and derivatives have been developed,19 the syntheses of phe-
nanthropyrazole compounds have been rarely reported. Reim-
linger20 synthesized 2H-phenanthro[9,10-c]pyrazole by the
reaction of diazofluorene with acetylene in an autoclave.
Alberti21 reported that diazotization of 4-(o-aminophenyl)-5-
phenylpyrazoles and treatment of the diazonium salt with
H3PO2 have given 2H-phenanthro[9,10-d]pyrazoles. 1-Phenyl-
1H-phenanthro[9,10-c]pyrazole has been synthesized by
irradiation of 1,4,5-triphenylpyrazole in the presence of
iodine.22 These synthetic processes are usually complicated,
time-consuming and carried out in the hazardous organic sol-
vents or under harsh conditions, even accompanied with
harmful by-products.
Following our investigations on the development of new
methodologies for the access to novel polyheterocyclic
aKey Laboratory of the Ministry of Education for Medicinal Resources and Natural
Pharmaceutical Chemistry, National Engineering Laboratory for Resource
Development of Endangered Crude Drugs in Northwest of China, and School of
Chemistry and Chemical Engineering, Shaanxi Normal University, Xi’an 710062,
PR China. E-mail: zhangzunting@sina.com; Fax: +86-29-85303940
Encouraged by the fact that Nayak and Wan23 obtained
photocyclization product triphenylene during the photolysis of
2′′-hydroxy[1,1′; 2′,1′′]terphenyl in 1 : 2 (v/v) H2O–CH3CN. We
attempted to synthesize 2H-phenanthro[9,10-c]pyrazoles 1 by
the photocyclization and dehydration of 3,4-diaryl-1H-pyra-
zoles 2. Herein, an environmentally friendly and efficient pro-
cedure for one-pot synthesis of 2H-phenanthro[9,10-c]pyrazoles
bCollege of Chemistry and Life Science, WeiNan Normal University, WeiNan 714000,
PR China
†Electronic supplementary information (ESI) available: 1H NMR, 13C NMR and
HRMS spectra for all compounds. See DOI: 10.1039/c3gc40205c
1048 | Green Chem., 2013, 15, 1048–1054
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Scheme 2 One-pot synthesis of 2H-phenanthro[9,10-c]pyrazoles.
1 from isoflavones 3 in EtOH was developed by two dehy- One-pot synthesis of 2H-phenanthro[9,10-c]pyrazoles
dration processes (Scheme 2).
During the cyclocondensation of isoflavone 3 with hydrazine
hydrate, EtOH was the best solvent according to literature.18
EtOH–H2O (1 : 1) was chosen as reaction medium for photo-
Results and discussion
Optimization of the solvents in photocyclization reaction
cyclization reactions. Hence, 2H-phenanthro[9,10-c]pyrazoles 1
were synthesized by one-pot procedure from isoflavone 3. First,
the intermediates 3,4-diaryl-1H-pyrazoles 2 were synthesized
by the cyclocondensation of isoflavones and 80% hydrazine
hydrate in refluxing EtOH. Three representative compounds
2a, 2b and 2t were synthesized in excellent yields (2a: 96%; 2b:
98%; 2t: 93%) according to literature methods.18 That is to say,
the electronic effect from the substrate had no significant
impact on the overall yields of 2. Then, the mixture was
directly adjusted to pH = 6–7 with a solution of 3 M HCl, and
diluted with 40 mL EtOH and 50 mL redistilled water. The
solution was irradiated with a medium-pressure mercury lamp
(500 W) under an argon atmosphere at about 20 °C. Finally,
2H-phenanthro[9,10-c]pyrazoles 1 were successfully obtained
by one-pot synthetic route (Scheme 2). The advantage of
one-pot synthesis mainly lies in its short routine, operational
simplicity and good yields.
According to the literature method,18 we synthesized the inter-
mediate 2a. The photocyclization reaction of 2a in different
solvents was investigated. It was found that only a trace of the
target product 1a was obtained when 2a was irradiated at λ ≥
300 nm with a medium-pressure mercury lamp (500 W) at
about 20 °C in Me2CO or CH2Cl2 for 12 h (trace, Table 1,
entries 1–2). And in EtOH, MeOH or MeCN, the photocycliza-
tion reaction was slow and the yield of product 1a was lower
after irradiating 2a for 6 h (32%–36%; Table 1, entries 3–5),
while the addition of same volume of water to them could
efficiently accelerate the reaction and increase its yield (74%–
82%, Table 1, entries 6–8), the reason is that the addition of
water is favorable to excited state intramolecular proton trans-
fer (ESIPT).23 From the economical and environmental point
of view, EtOH–H2O (1 : 1) was finally chosen as the reaction
medium for all further reactions.
Impact of different isoflavones on the yields of
Table 1 Photocyclization of 2a in different solventsa
photocyclization products
During the photocyclization of the intermediate 2, the elec-
tronic effect from the isoflavones 3 had a significant impact on
the yields of the product 1. The isoflavone skeletons carrying
electron-donating substituents including –Me, –OMe, –i-OPr or
–OH can react efficiently to give the corresponding products in
good yield (77–89%, Table 2, entries 2–15), while when they
carried the electron-withdrawing substituents such as –F, or
–CF3, the corresponding product is only obtained in lower
yields (32–68%, Table 2, entries 16–21). In addition, the posi-
tion of the substituents in the isoflavones also has an effect on
the yields of product 1. For an instance, in 3k and 3l, where
the electron-donating substituent –OMe was located on ring A
and ring B of the isoflavones, the yield of the corresponding
product 1k (84%, Table 2, entry 11) is higher than that of 1l
(76%, Table 2, entry 12). For another, 3p and 3r carried the
electron-withdrawing substituents –F: when –F was on ring A
of the isoflavone, the yield of 1p (38%, Table 2, entry 16) is
lower than 1r, in which –F was on ring B of the isoflavone
(64%, Table 2, entry 18). A conclusion can be drawn that the
impact of the substituents on ring B is less than that on ring A
in substrates.
Entry
Solvent
Time (h)
Yield 1b (%)
1
2
3
4
5
6
7
8
CH2Cl2
Me2CO
EtOH
MeOH
12 h
12 h
6 h
6 h
6 h
4 h
4 h
4 h
Trace
Trace
36%
32%
35%
82%
74%
80%
MeCN
EtOH–H2O (1 : 1)
MeOH–H2O (1 : 1)
MeCN–H2O (1 : 1)
a The intermediate 2a (0.236 g, 1 mmol) was dissolved in different
solvents (100 mL). The solution was irradiated at λ ≥ 300 nm with a
medium-pressure mercury lamp (500 W) under an argon atmosphere
at about 20 °C until 2a–u was consumed completely as indicated by
thin-layer chromatography (TLC). b Yield of isolated product after
column chromatography based on 2a.
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Table 2 One-pot synthesis of 2H-phenanthro[9,10-c]pyrazole compounds (1a–u) from isoflavones (3a–u) by two different dehydration processa
Entry
Substrate
R1
R2
R3
R4
Product
Timeb
Yieldc (%)
1
2
3
4
5
6
7
8
3a
3b
3c
3d
3e
3f
3g
3h
3i
3j
3k
3l
3m
3n
3o
3p
3q
3r
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
H
F
H
H
H
H
H
H
H
H
H
H
H
H
H
H
Me
H
H
H
H
H
H
H
H
1a
1b
1c
1d
1e
1f
1g
1h
1i
1j
1k
1l
1m
1n
1o
1p
1q
1r
6 h
3 h
3 h
3 h
4 h
4 h
6 h
4 h
6 h
6 h
4 h
5 h
4 h
4 h
4 h
12 h
10 h
8 h
8 h
12 h
12 h
75%
86%
89%
85%
83%
84%
79%
81%
78%
77%
84%
76%
82%
83%
86%
38%
46%
64%
68%
32%
33%
i-OPr
i-OPr
i-OPr
OH
OH
OMe
OH
OMe
OBz
OMe
H
Me
OMe
H
OH
OH
OMe
OMe
OMe
H
OMe
Me
Me
H
H
Me
F
F
CF3
CF3
9
10
11
12
13
14
15
16
17
18
19
20
21
H
OMe
OMe
H
H
H
OMe
OMe
i-OPr
F
H
H
H
H
3s
3t
3u
1s
1t
1u
a All reactions were carried out on the scale of 1 mmol 3a–u and 2 mmol 80% hydrazine hydrate in refluxing 10 mL EtOH until the complete
disappearance of 3a–u (1–3 h). The mixture was adjusted to pH = 6–7 with a solution of 3 M HCl, and diluted with 40 mL EtOH and 50 mL
redistilled water. The diluted solution was irradiated at λ ≥ 300 nm with a medium-pressure mercury lamp (500 W) under an argon atmosphere
at about 20 °C until 2a–u was consumed completely as indicated by TLC. b The photocyclization reaction time of 2a–u. c Yield of isolated product
after column chromatography based on 3a–u.
Mechanism for two dehydration processes
addition mechanism can be proposed for the cyclocondensa-
tion between isoflavones and hydrazine hydrate.24 First, one
nitrogen atom of hydrazine, as a nucleophile, attacks the C(2)
position of isoflavone A to produce the intermediate B, which
opens the benzopyranone ring to generate C. Another nitrogen
atom of hydrazine attacks the –CvO group, which, upon loss
of H2O and protonation, leads to condensation product D.
Then, under the radiation of UV light, the phenolic hydroxyl
group of D attacks the ortho-position of the other benzene ring
to give the addition products E; the intermediate E is unstable,
and loses H2O to obtain the final target products F.
A plausible mechanism for the formation of 2H-phenanthro-
[9,10-c]pyrazoles is depicted in Scheme 3. The Michael-
Tautomeric forms of 2H-phenanthro[9,10-c]pyrazoles
Being similar to pyrazoles,25 2H-phenanthro[9,10-c]pyrazoles
1
also exist in tautomeric forms (Scheme 4). For H NMR of 1b,
Scheme 3 Proposed mechanism for two dehydration processes.
1050 | Green Chem., 2013, 15, 1048–1054
Scheme 4 Alternative tautomeric forms of 2H-phenanthro[9,10-c]pyrazoles.
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with DMSO-d6 as solvent, a major proton peak at 13.9 ppm
accompanied by a minor peak at 13.6 ppm, and some small
Conclusions
peaks also appeared in the aromatic region; in DMSO-d6 with In summary, a novel protocol for one-pot syntheses of 2H-phe-
added D2O as solvent, the deuterium (2H)-exchange exper- nanthro[9,10-c]pyrazoles from isoflavones by two dehydration
iments simplified the spectra, and the peak at 13.9 ppm and processes in EtOH was developed. First, 3,4-diaryl-1H-pyrazoles
13.6 ppm disappeared. The results of deuterium (2H)-exchange were synthesized by the cyclocondensation of isoflavone and
of 1b indicated that 2H-phenanthro[9,10-c]pyrazoles has two hydrazine hydrate in refluxing EtOH, which was followed by a
1
tautomeric forms. In addition, the H NMR results of 2H-phe- photocyclization process in 1 : 1 EtOH–H2O to give the final
nanthro[9,10-c]pyrazoles showed that the type and position of target products 2H-phenanthro[9,10-c]pyrazoles. This pro-
the substituents in the 2H-phenanthro[9,10-c]pyrazoles cedure offers several notable advantages including operational
affected the ratios of tautomers. For examples, from the inte- simplicity, mild reaction conditions, excellent yields and being
gral areas of two proton peaks (13–14 ppm) at N atom, we can friendly to environment. It is an efficient method for one-pot
find the ratio of tautomers is 3 : 2 in 1o, 4.56 : 1 in 1b and 4 : 1 synthesis of the nitrogen-containing fused heterocycle
in 1s.
compounds. The fluorescence properties studies showed that
2H-phenanthro[9,10-c]pyrazoles had strong blue-purple
fluorescence.
Fluorescence properties of 2H-phenanthro[9,10-c]pyrazoles
2H-Phenanthro[9,10-c]pyrazoles have blue-purple fluorescence.
For 1, 1i, 1a and 1p were chosen to determine the fluorescence
properties. As is illustrated in Fig. 1, the maximum excitations
of 1i, 1a and 1p appear at 257, 255 and 253 nm, respectively,
which have a slight blue shift with the change of substituents
in 2H-phenanthro[9,10-c]pyrazoles. The photo-luminescence
spectra of 1a have a sharp emission peak at 361 nm
accompanied by two shoulders around 345 nm and 375 nm.
For 1p, it has the similar emission bands, which has an emis-
sion maxima of 358 nm with a slight blue shift compared with
its analogue 1a. While 1i has a red shift relative to analogue 1a
with the sharp emission peak of 375 nm and a shoulder of
373 nm. When there are electron-donating substituents on the
2H-phenanthro[9,10-c]pyrazole, its fluorescence intensity
increases obviously and the peak is red-shifted. When carrying
electron-with drawing substituents on the 2H-phenanthro-
[9,10-c]pyrazole, its fluorescence emission peak decreases sig-
nificantly in intensity and is blue-shifted in position.
Experimental section
Melting points were measured by a X-5 micromelting point
apparatus and are uncorrected. NMR spectra were recorded on
a Bruker AM 300 instrument or Bruker AM 400 instrument
using DMSO-d6 solvent peaks. High resolution mass spectra
(HRMS) was recorded using electron-spray ionization (ESI)
technique and IR spectra were recorded on a Nicollet 170SX
FT-IR spectrophotometer with KBr pellets. All the irradiation
experiments were performed in a BL-GHX-V photochemical
reactor equipped with a 500 W medium-pressure mercury
lamp. The fluorescent spectra were recorded on a Perkin Elmer
LS55 luminescence spectrometer. TLC was performed on silica
gel 60 GF254 plates. The silica gel (size 200–300 mesh) used
for the column chromatography was purchased from Qingdao
Haiyang Chemistry Plant (China).
General procedure for the synthesis of 2H-phenanthro[9,10-c]-
pyrazoles (1)
3,4-Diaryl-1H-pyrazoles were synthesized according to the lit-
erature method.18 Hydrazine hydrate (80%, 5 mmol) and iso-
flavone 3 (1 mmol) were added to an EtOH solution (10 mL)
and the mixture was refluxed at 80 °C until 3a–u was con-
sumed completely indicative by TLC (1–3 h). The mixture was
adjusted to pH = 6–7 with a solution of 3 M HCl, and diluted
with 40 mL EtOH and 50 mL redistilled water. The solution
was contained in 100 mL quartz tubes, deaerated by bubbling
Ar for 30 min and irradiated at λ ≥ 300 nm with a medium-
pressure mercury lamp (500 W), which were cooled to about
20 °C with tap water by means of an internal cold finger. The
progress of reaction was monitored by TLC at regular intervals
until the intermediate 2a–u had disappeared completely.
Then, the solvent was removed under reduced pressure, and
the residue was purified by column chromatography on silica
gel using petroleum ether–ethyl acetate or chloroform–metha-
nol to give the corresponding product (1a–u), and character-
ized by 1H NMR, 13C NMR, IR and HRMS.
Fig. 1 Excitation spectra (EX, dash lines) and emission spectra (EM, solid lines) of
compounds 1i (red), 1a (black) and 1p (blue) in chloroform (1 × 10−6 mol L−1).
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2H-Phenanthro[9,10-c]pyrazole (1a). Isolated as a yellow 125.0, 125.1, 128.6, 130.9, 131.5, 154.8, 156.5; IR (KBr), ν
powder; m.p. 242.3–244.9 °C. 1H NMR (300 MHz, DMSO-d6), (cm−1) 3262, 2922, 1628, 1587, 1462, 1230, 1084, 952, 758.
δ (ppm) 7.55 (s, 1H), 7.64–7.68 (m, 3H), 8.32 (s, 1H), 8.49 (s, HRMS (m/z): calc. for C15H10N2O2 [M + H]+ 251.0821, found
1H), 8.62–8.78 (m, 3H), 14.07 (br, 1H); 13C NMR (75 MHz, 251.0816.
DMSO-d6), δ (ppm) 116.2, 122.4, 123.8, 123.9, 124.1, 125.1,
9-Methoxy-2H-phenanthro[9,10-c]pyrazol-6-ol (1g). Isolated
126.9, 127.1, 127.2, 127.4, 127.6, 129.5; IR (KBr), ν (cm−1) 3403, as a pink powder; m.p. 241.6–243.2 °C. 1H NMR (400 MHz,
3098, 2922, 1611, 1544, 1455, 1197, 1075, 950, 862, 756. HRMS DMSO-d6), δ (ppm) 3.99 (s, 3H), 7.16 (d, 1H, J = 8.4 Hz), 7.34
(m/z): calc. for C15H10N2 [M + H]+ 219.0922, found 219.0910.
(d, 1H, J = 8.4 Hz), 7.99 (s, 2H), 8.11 (d, 1H, J = 8.4 Hz), 8.35 (d,
9-Isopropoxy-2H-phenanthro[9,10-c]pyrazole (1b). Isolated 1H, J = 8.4 Hz), 8.43 (s, 1H), 9.65 (s, 1H); 13C NMR (100 MHz,
1
as a yellow powder; m.p. 212.0–213.2 °C. H NMR (300 MHz, DMSO-d6), δ (ppm) 55.3, 106.3, 108.6, 115.4, 116.2, 117.3,
DMSO-d6), δ (ppm) 1.37 (d, 6H, J = 5.7 Hz), 4.98 (m, 1H), 7.38 119.9, 123.9, 125.0, 128.3, 130.7, 154.9, 158.2. IR (KBr), ν
(d, 1H, J = 7.5 Hz), 7.56 (m, 1H), 7.62 (m, 1H), 8.23 (s, 1H), 8.30 (cm−1) 3574, 3226, 2927, 2560, 1626, 1586, 1468, 1238, 1187,
(d, 1H, J = 7.5 Hz), 8.38 (d, 1H, J = 8.1 Hz), 8.55 (s, 1H), 8.76 (d, 1052, 950, 817; HRMS (m/z): calc. for C16H12N2O2 [M + H]+
1H J = 8.1 Hz), 13.89 (br, 1H); 13C NMR (75 MHz, DMSO-d6), δ 265.0977, found 265.0974.
(ppm) 21.9, 69.5, 108.9, 115.0, 115.2, 117.4, 123.6, 124.0,
6-Methoxy-2H-phenanthro[9,10-c]pyrazol-9-ol (1h). Isolated
1
124.2, 124.7, 126.7, 127.2, 127.6, 131.3, 133.8, 136.0, 156.7; IR as a brown powder; m.p. 268.8–270.0 °C. H NMR (300 MHz,
(KBr), ν (cm−1) 3689, 3155, 2928, 2358, 1714, 1475, 1202, 1061, DMSO-d6), δ (ppm) 3.96 (s, 3H), 7.23–7.27 (m, 2H), 7.96 (1s,
955, 758; HRMS (m/z): calc. for C18H16N2O [M + H]+ 277.1341, 1H), 8.06 (1s, 1H), 8.18 (d, 1H, J = 8.4 Hz), 8.30 (d, 1H, J =
found 277.1334.
8.4 Hz), 8.47 (s, 1H), 9.97 (s 1H); 13C NMR (75 MHz, DMSO-d6),
9-Isopropoxy-6-methyl-2H-phenanthro[9,10-c]pyrazole (1c). δ (ppm) 55.8, 106.7, 109.2, 115.2, 116.9, 117.5, 121.6, 124.4,
Isolated as an orange powder; m.p. 263.1–264.2 °C. 1H NMR 125.6, 128.5, 131.5, 157.1, 157.3; IR (KBr), ν (cm−1) 3630, 3435,
(300 MHz, DMSO-d6), δ (ppm) 1.36 (d, 6H, J = 6.0 Hz), 2.54 (s, 3207, 2599, 1627, 1465, 1236, 1056, 950, 811; HRMS (m/z): calc.
3H), 4.95 (m, 1H), 7.34 (d, 1H, J = 7.5 Hz), 7.45 (d, 1H, J = for C16H12N2O2 [M + H]+ 265.0977, found 265.0974.
7.8 Hz), 8.16 (d, 1H, J = 7.5 Hz), 8.20 (s, 1H), 8.35 (d, 1H, J =
6,9-Dimethoxy-2H-phenanthro[9,10-c]pyrazole (1i). Isolated
7.8 Hz), 8.48 (s, 1H), 8.55 (s, 1H), 13.81 (br, 1H); 13C NMR as a pink powder; m.p. 261.2–261.6 °C. 1H NMR (300 MHz,
(75 MHz, DMSO-d6), δ (ppm) 21.6, 69.5, 109.1, 115.1, 115.2, DMSO-d6), δ (ppm) 4.00 (s, 6H), 7.32 (br, 1H), 7.40 (br, 1H),
117.2, 123.5, 123.9, 124.0, 124.7, 126.7, 129.0, 131.1, 133.6, 8.15–8.20 (m, 3H), 8.38 (d, 1H, J = 8.4 Hz), 8.48 (s, 1H); 13C
133.9, 135.7, 156.6; IR (KBr), ν (cm−1) 3703, 3148, 3017, 2924, NMR (75 MHz, DMSO-d6), δ (ppm) 55.5, 107.1, 107.2, 115.1,
1719, 1584, 1461, 1258, 1177, 1122, 951, 856, 812, 759; HRMS 116.1, 116.3, 121.2, 123.9, 125.0, 128.1, 130.8, 156.9, 158.4; IR
(m/z): calc. for C19H18N2O [M + H]+ 291.1497, found 291.1480.
(KBr), ν (cm−1) 3688, 3142, 2906, 2358, 1732, 1627, 1469, 1285,
9-Isopropoxy-6-methoxy-2H-phenanthro[9,10-c]pyrazole(1d). 1239, 1189, 1032, 949, 861, 809; HRMS (m/z): calc. for
Isolated as a pink powder; m.p. 248.1–249.0 °C. 1H NMR C17H14N2O2 [M + H]+ 279.1134, found 279.1131.
(300 MHz, DMSO-d6), δ (ppm) 1.36 (d, 6H, J = 6.0 Hz), 3.94 (s,
9-Benzyloxy-6-methoxy-2H-phenanthro[9,10-c]pyrazole (1j).
3H), 4.96 (m, 1H), 7.27 (d, 1H, J = 7.2 Hz), 7.37 (d, 1H, J = 7.2 Isolated as a pink powder; m.p. 277.8–279.9 °C. 1H NMR
Hz), 8.10–8.18 (m, 3H), 8.36 (d, 1H, J = 8.1 Hz), 8.45 (s, 1H), (400 MHz, DMSO-d6), δ (ppm) 3.98 (s, 3H), 5.38 (s, 2H),
13.77 (br, 1H); 13C NMR (75 MHz, DMSO-d6), δ (ppm) 21.9, 7.27–7.45 (m, 5H), 7.58 (m, 2H), 8.10 (s, 1H), 8.19 (d, 1H, J =
55.5, 69.5, 106.8, 109.7, 115.2, 115.3, 116.6, 117.1, 121.0, 123.9, 8.0 Hz), 8.28 (s, 1H), 8.39 (d, 1H, J = 8.0 Hz), 8.49 (s, 1H), 13.77
124.9, 128.0, 130.9, 133.2, 135.1, 156.5, 156.9; IR (KBr), ν (s, 1H); 13C NMR (100 MHz, DMSO-d6), δ (ppm) 55.5, 69.7,
(cm−1) 3702, 3094, 2980, 2916, 1720, 1582, 1460, 1277, 1185, 106.9, 108.4, 115.2, 116.5, 116.6, 116.7, 121.2, 123.9, 125.0,
1122, 957, 861, 817; HRMS (m/z): calc. for C19H18N2O2 [M + H]+ 127.9, 128.4, 130.8, 137.1, 156.9, 157.5; IR (KBr), ν (cm−1) 3685,
307.1447, found 307.1430.
3134, 2926, 2358, 1624, 1586, 1467, 1237, 1188, 1064, 1033,
2H-Phenanthro[9,10-c]pyrazol-9-ol (1e). Isolated as a pink 951, 824, 736. HRMS (m/z): calc. for C22H18N2O2 [M + H]+
1
powder; m.p. 279.2–280.1 °C. H NMR (300 MHz, DMSO-d6), δ 355.1447, found 355.1445.
(ppm) 7.22 (m, 1H), 7.51–7.61 (m, 2H), 8.05 (s, 1H), 8.26–8.31
9-Methoxy-2H-phenanthro[9,10-c]pyrazole (1k). Isolated as
(m, 3H), 8.51 (s, 1H), 10.00 (s, 1H), 13.79 (s, 1H); 13C NMR an orange powder; m.p. 254.1–255.7 °C. 1H NMR (300 MHz,
(75 MHz, DMSO-d6), δ (ppm) 108.4, 114.7, 116.9, 123.7, 123.9, DMSO-d6), δ (ppm) 4.00 (s, 3H), 7.37 (s, 1H), 7.54 (s, 1H), 7.63
124.8, 127.5, 131.4, 133.7, 133.8, 133.9, 156.8; IR (KBr), (s, 1H), 8.21 (s, 1H), 8.29 (s, 1H), 8.40 (s, 1H), 8.58 (br, 1H),
ν (cm−1) 3159, 2923, 1706, 1623, 1458, 1321, 1195, 1085, 947, 8.75 (s, 1H), 13.88 (s, 1H); 13C NMR (75 MHz, DMSO-d6), δ
847, 754; HRMS (m/z): calc. for C15H10N2O [M + H]+ 235.0871, (ppm) 55.5, 106.6, 115.1, 116.3, 123.7, 123.9, 124.2, 124.8,
found 235.0858.
127.6, 131.2, 133.8, 133.9, 158.6; IR (KBr), ν (cm−1) 3699, 3100,
2H-Phenanthro[9,10-c]pyrazole-6,9-diol (1f). Isolated as a 2925, 1728, 1621, 1584, 1474, 1225, 1031, 950, 857, 756; HRMS
1
grey powder; m.p. 324.6–325.2 °C. H NMR (300 MHz, DMSO- (m/z): calc. for C16H12N2O [M + H]+ 249.1028, found 249.1014.
d6), δ (ppm) 7.18–7.22 (m, 2H), 7.85 (d, 2H, J = 8.4 Hz), 8.11 (d,
6-Methoxy-2H-phenanthro[9,10-c]pyrazole (1l). Isolated as a
1
1H, J = 7.5 Hz), 8.28 (d, 1H, J = 8.4 Hz), 8.40 (s, 1H), 9.62 (s, pink powder; m.p. 245.4–246.7 °C. H NMR (300 MHz, DMSO-
1H), 9.92 (s, 1H), 13.62 (s, 1H); 13C NMR (75 MHz, DMSO-d6), δ d6), δ (ppm) 3.97 (s, 3H), 7.30 (br, 1H), 7.69–7.73 (m, 2H),
(ppm) 108.1, 108.2, 114.9, 116.8, 117.1, 117.2, 119.9, 123.9, 8.19–8.24 (m, 2H), 8.44–8.84 (m, 3H), 13.95 (br, 1H); 13C NMR
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(75 MHz, DMSO-d6), δ (ppm) 55.4, 106.5, 116.4, 116.6, 120.7, 1H), 8.46–8.59 (m, 3H), 8.78 (s, 1H), 14.08 (br, 1H); 13C NMR
121.3, 122.3, 124.5, 125.0, 126.8, 127.4, 128.3, 129.0, 133.3, (75 MHz, DMSO-d6), δ (ppm) 109.4, 109.6, 115.7, 115.9, 121.3,
134.9, 157.1; IR (KBr), ν (cm−1) 3138, 3006, 2946, 1714, 1622, 122.4, 123.5, 124.7, 125.8, 127.2, 128.0, 128.8, 133.8, 135.5,
1581, 1458, 1243, 1207, 1071, 1032, 952, 865, 825, 767; HRMS 160.9; IR (KBr), ν (cm−1) 3705, 3097, 2920, 1716, 1625, 1462,
(m/z): calc. for C16H12N2O [M + H]+ 249.1028, found 249.1006.
6-Methyl-2H-phenanthro[9,10-c]pyrazole (1m). Isolated as calc. for C15H9FN2 [M + H]+ 237.0828, found 237.0812.
an orange powder; m.p. 256.2–257.5 °C. 1H NMR (400 MHz,
6-Fluoro-9-methoxy-2H-phenanthro[9,10-c]pyrazole (1s). Iso-
1378, 1277, 1231, 1188, 1127, 1064, 952, 855, 824; HRMS (m/z):
DMSO-d6), δ (ppm) 2.55 (s, 3H), 7.46 (d, 1H, J = 8.0 Hz), lated as a yellow powder; m.p. 310.8–311.6 °C. 1H NMR
7.65–7.72 (m, 2H), 8.20 (d, 1H, J = 8.0 Hz), 8.46 (d, 1H, J = (400 MHz, DMSO-d6), δ (ppm) 4.00 (s, 3H), 7.39 (d, 1H, J =
8.0 Hz), 8.54 (s, 1H), 8.59 (s, 1H), 8.78 (d, 1H, J = 8.0 Hz); 8.0 Hz), 7.50 (m, 1H), 8.18 (s, 1H), 8.31–8.39 (m, 2H), 8.53 (s,
13C NMR (100 MHz, DMSO-d6), δ (ppm) 21.4, 116.4, 121.1, 1H), 8.60 (d, 1H, J = 8.0 Hz), 13.89 (br, 1H); 13C NMR (75 MHz,
122.3, 123.6, 123.7, 123.9, 124.1, 124.4, 127.0, 127.2, 128.9, DMSO-d6), δ (ppm) 55.6, 106.9, 109.8, 110.0, 114.8, 115.4,
129.3, 133.7, 134.2, 135.5; IR (KBr), ν (cm−1) 3700, 3096, 2910, 115.8, 117.2, 123.9, 125.7, 128.4, 130.6, 133.7, 135.6, 158.6,
1582, 1455, 1194, 1074, 951, 820, 764; HRMS (m/z): calc. for 159.1; IR (KBr), ν (cm−1) 3684, 3097, 2924, 1716, 1626, 1469,
C16H12N2 [M + H]+ 233.1079, found 233.1072.
1377, 1274, 1228, 1179, 1067, 1033, 954, 862, 815. HRMS (m/z):
(1n). calc. for C16H12FN2O [M + H]+ 267.0934, found 267.0913.
9-Methoxy-6-methyl-2H-phenanthro[9,10-c]pyrazole
Isolated as an orange powder; m.p. 238.2–238.8 °C. 1H NMR
9-Methoxy-6-trifluoromethyl-2H-phenanthro[9,10-c]pyrazole
(300 MHz, DMSO-d6), δ (ppm) 2.55 (s, 3H), 4.00 (s, 3H), 7.34 (1t). Isolated as a yellow powder; m.p. 232.1–233.7 °C. 1H
(s, 1H), 7.43 (s, 1H), 8.16 (br, 2H), 8.36 (1s, 1H), 8.53 (br, 2H), NMR (300 MHz, DMSO-d6), δ (ppm) 4.03 (s, 3H), 7.43 (br, 1H),
13.81 (s, 1H); 13C NMR (75 MHz, DMSO-d6), δ (ppm) 21.3, 7.91 (d, 1H, J = 8.1 Hz), 8.28–8.54 (m, 3H), 8.66 (s, 1H), 9.05
55.5, 106.5, 115.2, 116.2, 123.5, 123.9, 124.0, 124.8, 126.7, (br, 1H), 14.03 (s, 1H); 13C NMR (75 MHz, DMSO-d6), δ (ppm)
127.2, 127.2, 128.9, 131.1, 133.5, 133.6, 133.9, 158.5; IR (KBr), 55.7, 106.9, 114.4, 117.4, 121.6, 123.4, 124.1, 124.7, 125.7,
ν (cm−1) 3387, 3097, 2922, 1633, 1584, 1465, 1281, 1229, 1070, 127.4, 127.5, 128.6, 130.6, 134.5, 136.9, 158.9; IR (KBr), ν
951, 861, 816; HRMS (m/z): calc. for C17H14N2O [M + H]+ (cm−1) 3684, 3145, 2933, 1715, 1625, 1588, 1476, 1326, 1280,
263.1184, found 263.1182.
1121, 1031, 949, 829, 775; HRMS (m/z): calc. for C17H11F3N2O
(1o). [M + H]+ 317.0902, found 317.0876.
9-Methoxy-11-methyl-2H-phenanthro[9,10-c]pyrazole
Isolated as a white powder; m.p. 240.2–241.1 °C. 1H NMR
9-Isopropoxy-6-trifluoromethyl-2H-phenanthro[9,10-c]pyrazole
(300 MHz, DMSO-d6), δ (ppm) 3.01 (s, 3H), 3.98 (s, 3H), 7.17 (1u). Isolated as a yellow powder; m.p. 263.7–265.2 °C. 1H
(s, 1H), 7.54 (br, 2H), 8.05 (br, 1H), 8.26 (br, 1H), 8.68–8.81 (m, NMR (400 MHz, DMSO-d6), δ (ppm) 1.36 (d, 6H, J = 6.0 Hz),
2H), 13.68 (br, 1H); 13C NMR (75 MHz, DMSO-d6), δ (ppm) 5.03 (m, 1H), 7.41 (s, 1H), 7.89 (d, 1H, J = 7.2 Hz), 8.10–8.46
24.3, 55.2, 104.6, 115.9, 117.7, 122.4, 125.1, 127.4, 127.6, 132.4, (m, 3H), 8.62 (s, 1H), 9.03 (br, 1H), 14.02 (br, 1H); 13C NMR
132.5, 135.5, 137.2, 157.5; IR (KBr), ν (cm−1) 3251, 2954, 1613, (75 MHz, DMSO-d6), δ (ppm) 21.8, 69.7, 109.6, 114.4, 118.2,
1462, 1204, 1074, 941, 840, 743; HRMS (m/z): calc. for 121.5, 121.6, 123.4, 124.1, 124.7, 125.3, 126.1, 127.4, 130.7,
C17H14N2O [M + H]+ 263.1184, found 263.1179.
134.4, 134.5, 157.1; IR (KBr), ν (cm−1) 3686, 3146, 2981, 2932,
10-Fluoro-2H-phenanthro[9,10-c]pyrazole (1p). Isolated as a 1714, 1625, 1586, 1471, 1378, 1324, 1180, 1120, 952, 829, 774;
yellow powder; m.p. 229.6–230.9 °C. 1H NMR (300 MHz, HRMS (m/z): calc. for C19H15F3N2O [M + H]+ 345.1215, found
DMSO-d6), δ (ppm) 7.56–7.65 (m, 3H), 8.24–8.33 (m, 2H), 345.1196.
8.63–8.70 (m, 2H), 8.86 (s, 1H), 14.05 (s, 1H); 13C NMR
(75 MHz, DMSO-d6), δ (ppm) 107.4, 107.6, 115.1, 115.3, 117.0.,
123.7, 123.8 125.3, 126.2, 127.4, 131.4, 134.0, 134.1, 135.3,
Acknowledgements
159.9; IR (KBr), ν (cm−1) 3698, 3107, 2920, 1720, 1622, 1584,
1459, 1175, 1075, 951, 870, 763; HRMS (m/z): calc. for The research was supported by the National Natural Science
C15H9N2F [M + H]+ 237.0828, found 237.0811.
Foundation of China (No. 20772076), the Fundamental Funds
10-Fluoro-6-methyl-2H-phenanthro[9,10-c]pyrazole (1q). Iso- Research for the Central Universities (No. Gk200901010),
lated as an orange powder; m.p. 292.3–293.4 °C. 1H NMR Innovation Funds of Graduate Programs (No. 2012CXB016)
(300 MHz, DMSO-d6), δ (ppm) 2.54 (s, 3H), 7.48–7.52 (m, 2H), and Work-Study Scientific Research Innovation Funds
8.19 (br, 2H), 8.50–8.57 (m, 2H), 8.84 (br, 1H), 13.97 (br, 1H); (No. QZZD12064) of Shaanxi Normal University.
13C NMR (75 MHz, DMSO-d6), δ (ppm) 21.4, 107.4, 107.5,
115.0, 115.1, 117.0, 123.7, 123.8, 123.9, 126.0, 126.7, 127.1,
128.8, 133.8, 134.5, 160.2; IR (KBr), ν (cm−1) 3686, 3146, 2923,
Notes and references
1714, 1627, 1550, 1464, 1378, 1178, 1083, 950, 865, 819, 773;
HRMS (m/z): calc. for C17H11FN2 [M + H]+ 251.0985, found
251.0968.
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