Three component solvent-free synthesis of 1H-pyrazol-5(4H)-one-based heterocyclic ketene aminal derivatives

Article abstract of DOI:10.1039/c3ra41547c

An efficient one-pot three-component synthesis of novel 1H-pyrazol-5(4H)-one-based heterocyclic ketene aminal libraries was performed by simply refluxing a mixture of heterocyclic ketene aminals (HKAs), 1-phenyl-1H-pyrazol-5(4H)-ones and triethoxymethane under solvent-free and catalyst-free conditions. The protocol has the advantages of being highly efficient and environmentally benign, with excellent yields and easy work-up, making it suitable for large-scale and parallel combination synthesis. These compounds are promising candidates for drug discovery. Consequently, a library of diverse 1H-pyrazol-5(4H)-one-based HKAs was rapidly constructed using this method.

Full text of DOI:10.1039/c3ra41547c

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Three component solvent-free synthesis of 1H-pyrazol-
5(4H)-one-based heterocyclic ketene aminal
derivatives3
Cite this: RSC Advances, 2013, 3,
13183
Fuchao Yu,a Zhiqiong Chen,a Xiaopan Hao,a Xiuyang Jiang,a Shengjiao Yan*a
and Jun Lin*ab
An efficient one-pot three-component synthesis of novel 1H-pyrazol-5(4H)-one-based heterocyclic ketene
aminal libraries was performed by simply refluxing a mixture of heterocyclic ketene aminals (HKAs),
1-phenyl-1H-pyrazol-5(4H)-ones and triethoxymethane under solvent-free and catalyst-free conditions.
The protocol has the advantages of being highly efficient and environmentally benign, with excellent
yields and easy work-up, making it suitable for large-scale and parallel combination synthesis. These
compounds are promising candidates for drug discovery. Consequently, a library of diverse 1H-pyrazol-
5(4H)-one-based HKAs was rapidly constructed using this method.
Received 30th March 2013,
Accepted 13th May 2013
DOI: 10.1039/c3ra41547c
www.rsc.org/advances
Consequently, the search for efficient, concise and envir-
onmentally friendly methods for the synthesis of this type of
compound is an interesting field in chemistry.
Introduction
The major challenges in modern drug discovery at the
beginning of 21st century are the design of highly efficient
protocols to provide structural complexity and diversity in
compounds. Recently, more and more strategies and technol-
ogies have been developed to obtain novel compounds to meet
the demands of drug chemists. Multicomponent reactions
(MCRs) have been widely studied, which allow the quick
assembly of several simple components into complex struc-
tures in one pot.1 MCRs are powerful tools in the modern drug
discovery process.2 In addition, solvent-free conditions (SFC)
have been used with great success, thus avoiding complicated
and time-consuming purification operations.3
Heterocyclic ketene aminals (HKAs) are versatile building
blocks in heterocyclic synthesis,11 which have been widely
used in the synthesis of heterocyclic compounds including
anticancer agents,12 herbicides, pesticides,13 antianxiety
agents,14 antileishmanial agents,15 and antibacterial and
antitherapeutic drugs.16 Our group have a long-standing
interest in this field, and we have developed MCRs to obtain
compounds with these biological activities using a convenient
and rapid synthetic procedure.12 Encouraged by these results,
we believe that hybrid molecules based on pyrazolone and
HKAs maybe have potent biological activity.
Pyrazolone is a structural motif present in many important
natural products and synthetic drugs.4 The heterocyclic
nucleus containing pyraolones, such as edaravone (MCI-186,
Fig. 1), has been widely used for treating brain5 and
myocardial ischemia.6 Phenazone and propheazone (Fig. 1)
have been widely used as antipyretic and analgesic agents.7
Recently, medical chemists have begun to pay attention to the
a,b-unsaturated pyrazolones, which have potent bioactivities
such as HIV-1 integrase inhibition8 (compound A, Fig. 1), BAF-
3/TPO luciferase activity9 (compound B), and so on.10
aKey Laboratory of Medicinal Chemistry for Natural Resource (Yunnan University),
Ministry of Education, School of Chemical Science and Technology, Yunnan
University, Kunming, 650091, P. R. China. E-mail: yansj@ynu.edu.cn;
linjun@ynu.edu.cn; Fax: +86 871 65033215
bState Key Laboratory of Elemento-organic Chemistry, Nankai University, Tianjin,
300071, P. R. China
Electronic supplementary information (ESI) available: CCDC 917318. For ESI
3
and crystallographic data in CIF or other electronic format see DOI: 10.1039/
c3ra41547c
Fig. 1 Some biologically active pyrazolones and a,b-unsaturated pyrazolones.
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The structure of HKAs is described in Fig. 2, with the
RSC Advances
Table 1 Optimization of the reaction conditionsa
conjugation of electro-donating amino groups and the
electron-withdrawing carbonyl group. Thus, HKAs have a
highly polarized double bond (CLC).11a,11b This leads to the
electron density of the a-carbon (C3) being higher than that of
the secondary amino groups (N1 and N5). As a result, the
substituted targets of the a-carbon have been obtained with
high selectivity via alkylation,17 acylation,18 glycosylation19
and halogenation reactions.20 However, the selective forma-
tion of a,b-unsaturated double bonds via MCRs has not been
reported to date (Fig. 2).
We believe that these hybrid molecules, with a combination
of the pharmaceutical properties of pyrazolone and the
biological activities of HKAs, may have potent activities. So,
an efficient and concise one-pot MCR approach to obtain
novel regio- and stereoselective targets is particularly promis-
ing as well as strongly desired.
Entry Solvent
Catalyst
t (uC)
Time (min) Yieldb (%)
1
2
3
4
5
6
7
8
Water
EtOH
MeCN
Dioxane
EtOH
EtOH
EtOH
EtOH
—
—
—
—
Reflux 10
Reflux 10
Reflux 10
Reflux 10
Reflux 10
Reflux 10
Reflux 10
Reflux 10
n.r.
85
83
78
n.r.
68
t-BuOK
p-TSA
AcOH
L-pyridine
—
83
30
9
—
110
10
93
Herein, we describe a facile, eco-friendly method for
efficient synthesis of a,b-unsaturated pyrazolone-based HKAs
in SFC based on MCRs of HKAs, triethoxymethane and
3-pyrazol-5(4H)-ones. This method has some advantages such
as high yields, a broad scope, time efficiency and easy work-up.
a
The reaction was performed with 1a (1 mmol), 4 (2 mmol), 5a (1.2
b
mmol) and the solvent (15 mL) under reflux. Isolated yield based
on HKA 1a. n.r. = no reaction.
With the optimization conditions in hand, we wanted to
examine the scope and limitations of this method. Thus, a
number of five-membered ring HKAs 1b–1f were used as
substrates to react with triethoxymethane 4 and pyrazolones
5a–5b (Table 2, entries 2–12). The results demonstrate that the
five-membered HKAs, with various substituents, were all good
substrates for the cascade reaction in one pot (Table 2, entries
1–12). The reactions usually took 10 min at 110 uC to complete,
and gave the products in excellent yields. Based on this, other
five-membered HKAs 1g and 1h were reacted with triethox-
ymethane 4 and 3-methyl-1-phenyl-1H-pyrazol-5(4H)-one 5a
under the same conditions (Scheme 1), and also gave the
target compounds in good yields. All in all, various substituted
HKAs could be smoothly reacted with substrates 4 and 5 to
obtain the target compounds in good to excellent yields (82–
95%) (Table 2, entries 1–12, and Scheme 1).
Results and discussion
First, the MCR reaction of HKA 1a, triethoxymethane 4 and
3-methyl-1-phenyl-1H-pyrazol-5(4H)-one 5a was evaluated. The
materials were composed of a 1 : 2 : 1.2 ratio of 1a : 4 : 5a,
which were treated under various conditions including
different solvents and catalysts (Table 1, entries 1–9). The
results indicate that the reaction could not proceed in water
(Table 1, entry 1), nor could it proceed in the presence of
t-BuOK in EtOH (Table 1, entry 5). We obtained the target
compound 6a under solvent-free and catalyst-free conditions
with the best yield of 93% (Table 1, entry 9). Solvent-free
conditions are optimal to prepare these target compounds.
The product was carefully identified by spectroscopic data and
high-resolution mass spectroscopy.
Fig. 2 Routes based on the one-pot cascade reaction of HKAs to give 1H-pyrazol-5(4H)-one-based HKA derivatives.
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Table 2 Preparation of 1H-pyrazol-5(4H)-one-based HKA derivative 6a
Entry
R1
R2
1
5
6
Yieldb(%)
1
2
3
4
5
6
7
8
p-OMe
p-Me
H
p-Cl
p-F
o-Cl
p-OMe
p-Me
H
p-Cl
p-F
CH3
CH3
CH3
CH3
CH3
CH3
CF3
CF3
CF3
CF3
CF3
CF3
1a
1b
1c
1d
1e
1f
1a
1b
1c
1d
1e
1f
5a
5a
5a
5a
5a
5a
5b
5b
5b
5b
5b
5b
6a
6b
6c
6d
6e
6f
6g
6h
6i
93
92
90
87
85
85
95
94
93
92
88
90
9
10
11
12
6j
6k
6l
o-Cl
a
b
The reaction was performed with 1 (1 mmol), 4 (2 mmol), and 5 (1.2 mmol). Isolated yield based on HKA 1.
Encouraged by these results, ring size was also investigated
in our work. Thus, the six-membered HKAs 2a–2f were reacted
with triethoxymethane 4 and pyrazolones 5a–5b (Table 3,
entries 1–12). At the same time, multifunctional pyrazolone 5c
was used as the substrate and reacted with HKA 2b and
triethoxymethane 4 under the same conditions. We also
obtained compound 7m in excellent yield (Scheme 2). On
the whole, the six-membered HKAs provided higher yields
than those of the five-membered HKAs (Table 2 and Scheme 1
vs. Table 3 and Scheme 2).
To explore the scope and limitations of this method, the
seven-membered HKAs 3a–3e were used as substrates to react
with triethoxymethane 4 and pyrazolones 5a–5b (Table 4,
entries 1–10).
We concluded that HKAs, with various substituents and
different ring sizes, were all good substrates for the cascade
reaction in one pot (Tables 2–4 and Schemes 1–2). The
reactions were complete in about 10 min at 110 uC, and
provided products in excellent yields (82–96%). In general, the
different substituents of the same ring sizes of HKAs provided
similar yields (Table 2, entries 1–12; Table 3, entries 1–12;
Table 4, entries 1–10). On the whole, the seven-membered
HKAs were more favorable in terms of yields than the five-
membered or six-membered HKAs (Table 4 vs. Table 2 and
Table 3).
To verify the structure of the product 1H-pyrazol-5(4H)-one-
based HKAs, 6c was selected as a representative compound
and characterized by X-ray crystallography, as shown in Fig. 3
(CCDC 917318).21
A proposed mechanism for the cascade reaction is depicted
in Scheme 3. HKA 1c reacted with triethoxymethane 4 to form
intermediate 9 via an aza-ene reaction mechanism22 and lost
one molecular ethanol. Then, 9 underwent a process of imine–
enamine tautomerization to obtain compound 10. 3-Methyl-1-
phenyl-1H-pyrazol-5(4H)-one 5a gave 11 though keto-enol
tautomerism. Intermediate 10 reacted with 11 to form
compound 12 via an aldol condensation accompanied by the
loss of one molecular ethanol. Finally, 12 formed the final
product 6c by an aromatization mechanism.
Conclusions
To summarize, we have developed a method for the synthesis
of diverse 1H-pyrazol-5(4H)-one-based HKAs with potent
bioactivity using a one-pot three-component reaction. By this
method, a diverse 1H-pyrazol-5(4H)-one-based HKA library was
rapidly constructed with excellent regio- and cis/trans stereo-
selectivity by simply heating a mixture of HKA, triethoxy-
Scheme 1 One-pot synthesis of HKA derivatives 6m–6n.
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Table 3 One-pot synthesis of 1H-pyrazol-5(4H)-one-based HKA derivative 7 under solvent-free conditionsa
Entry
R1
R2
2
5
7
Yieldb(%)
1
2
3
4
5
6
7
8
p-OMe
p-Me
H
p-Cl
p-F
o-Cl
p-OMe
p-Me
H
p-Cl
p-F
CH3
CH3
CH3
CH3
CH3
CH3
CF3
CF3
CF3
CF3
CF3
CF3
2a
2b
2c
2d
2e
2f
2a
2b
2c
2d
2e
2f
5a
5a
5a
5a
5a
5a
5b
5b
5b
5b
5b
5b
7a
7b
7c
7d
7e
7f
7g
7h
7i
95
95
93
92
90
91
96
95
92
91
89
91
9
10
11
12
7j
7k
7l
o-Cl
a
b
The reaction was performed with 2 (1 mmol), 4 (2 mmol) and 5 (1.2 mmol). Isolated yield based on HKA 2.
apparatus and are uncorrected. High resolution mass spectro-
metry (HRMS) was performed on an Agilent LC/MSD TOF and
monoisotopic mass instrument. All chemicals and solvents
were used as received without further purification unless
otherwise stated. Column chromatography was performed on
silica gel (200–300 mesh). The raw materials 1–3 were
synthesized according to the literature.23
General procedure. HKAs 1–3 (1.0 mmol), triethoxymethane
4 (2.0 mmol) and 1-phenyl-1H-pyrazol-5(4H)-one derivatives 5
(1.2 mmol) were placed into a 25 mL round-bottom flask and
the mixture was heated to 110 uC for about 10 min and
monitored by TLC until the HKA substrate was used up. Then
the reaction mixture was cooled to room temperature, filtered
and washed with 95% EtOH to give the pure product with 82–
96% yield. The products were further identified by FT-IR, NMR
and HRMS, being in good agreement with the assigned
structures.
methane and pyrazolones under solvent-free and catalyst-free
conditions. Furthermore, the generality with respect to the
substrate scope and facile accessibility to the starting
materials are also highly appealing.
Experimental
General information
All compounds were fully characterized by spectroscopic
methods. NMR spectra were recorded on a Bruker DRX400
or DRX500, chemical shifts (d) are expressed in ppm, and J
values are given in Hz; DMSO-d6 and CDCl3 were used as
solvents. IR spectra were recorded on a FT-IR Thermo Nicolet
Avatar 360 using a KBr pellet. The reactions were monitored by
thin-layer chromatography (TLC) using silica gel GF254. The
melting points were determined on XT-4A melting point
(Z)-4-(2-(Imidazolidin-2-ylidene)-3-(4-methoxyphenyl)-3-oxo-
propylidene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6a).
Saffron yellow solid; m.p. 204–205.5 uC; IR (KBr): 3307, 2965,
1625, 1593, 1496, 1427, 1392, 1294, 1252, 1176, 1127, 992, 841,
765 cm21; 1H NMR (400 MHz, DMSO-d6): d = 1.95 (s, 3H, CH3),
3.76–3.79 (m, 4H, NCH2CH2N), 3.78 (s, 3H, OCH3), 6.95–6.97
(m, 2H, ArH), 7.00–7.04 (m, 1H, ArH), 7.28–7.32 (m, 2H, ArH),
7.42 (s, 1H, CH), 7.52–7.55 (m, 2H, ArH), 7.89–7.91 (m, 2H,
ArH), 9.67 (br, 2H, NH); 13C NMR (100 MHz, DMSO-d6): d =
13.3 (CH3), 43.4 (NCH2), 43.4 (CH2N), 55.3 (OCH3), 113.3,
117.9, 122.9, 128.5, 130.8, 130.8 (LCH), 132.7, 139.9, 142.9,
150.4, 161.4 (HNCL), 162.8 (CH3OCL), 165.9 (NCLO), 191.8
(CLO); HRMS (EI): m/z calcd for C23H22N4O3 [M], 402.1692;
found, 402.1690.
(Z)-4-(2-(Imidazolidin-2-ylidene)-3-oxo-3-p-tolylpropylid-
ene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6b). Saffron yel-
Scheme 2 One-pot synthesis of HKA derivative 7m.
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Table 4 One-pot synthesis of 1H-pyrazol-5(4H)-one-based HKA derivative 7 under solvent-free conditionsa
Entry
R1
R2
3
5
8
Yieldb(%)
1
2
3
4
5
6
7
8
9
10
p-OMe
p-Me
H
p-Cl
o-Cl
p-OMe
p-Me
H
CH3
CH3
CH3
CH3
CH3
CF3
CF3
CF3
CF3
CF3
3a
3b
3c
3d
3e
3a
3b
3c
3d
3e
5a
5a
5a
5a
5a
5a
5b
5b
5b
5b
8a
8b
8c
8d
8e
8f
8g
8h
8i
96
95
94
93
93
96
96
96
94
94
p-Cl
o-Cl
8j
a
b
The reaction was performed with 3 (1 mmol), 4 (2 mmol) and 5 (1.2 mmol). isolated yield based on HKA 3a.
low solid; m.p. 238–241 uC; IR (KBr): 3321, 1625, 1593, 1496,
1397, 1257, 1185, 1128, 1048, 990, 763 cm21 1H NMR (500
138.8, 140.8, 147.9, 152.8, 163.5 (HNCL), 165.5 (NCLO), 198.1
(CLO); HRMS (EI): m/z calcd for C22H20N4O2 [M], 372.1586;
found, 372.1590.
;
MHz, DMSO-d6 + HClO4): d = 2.26 (s, 3H, CH3), 2.33 (s, 3H,
CH3), 3.82–3.85 (m, 4H, NCH2CH2N), 7.27–7.29 (m, 3H, CH
and ArH), 7.43–7.49 (m, 5H, ArH), 7.59–7.61 (m, 2H, ArH), 9.72
(br, 2H, NH); 13C NMR (125 MHz, DMSO-d6 + HClO4): d = 11.5
(CH3), 21.4 (PhCH3), 44.4 (NCH2), 44.4 (CH2N), 100.8, 114.3,
120.9, 126.7, 129.4, 129.5, 129.5 (LCH), 135.2, 135.7, 139.7,
143.3, 150.7, 158.8 (HNCL), 165.7 (NCLO), 191.8 (CLO); HRMS
(EI): m/z calcd for C23H22N4O2 [M], 386.1743; found, 386.1735.
(Z)-4-(2-(Imidazolidin-2-ylidene)-3-oxo-3-phenylpropylid-
ene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6c). Saffron yel-
low solid; m.p. 231–235 uC; IR (KBr): 3288, 2878, 1623, 1585,
(Z)-4-(3-(4-Chlorophenyl)-2-(imidazolidin-2-ylidene)-3-oxo-
propylidene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6d).
Saffron yellow solid; m.p. 233–237 uC; IR (KBr): 3321, 2886,
1631, 1591, 1494, 1428, 1392, 1254, 1182, 1128, 1088, 1044,
993, 823, 763 cm21; 1H NMR (400 MHz, DMSO-d6): d = 2.27 (s,
3H, CH3), 3.81–3.86 (m, 4H, NCH2CH2N), 7.23–7.26 (m, 1H,
ArH), 7.41–7.45 (m, 4H, ArH), 7.47–7.50 (m, 3H, ArH), 7.52 (s,
1H, CH), 7.67–7.69 (m, 2H, ArH), 9.71 (br, 2H, NH); 13C NMR
(100 MHz, DMSO-d6): d = 11.2 (CH3), 44.0 (NCH2), 44.0 (CH2N),
100.9, 112.5, 120.5, 126.2, 128.5, 129.1, 129.2, 130.9, 135.4,
136.5, 137.2, 150.5, 158.6 (HNCL), 165.1 (NCLO), 190.6 (CLO);
1495, 1428, 1258, 1130, 1037, 994, 751 cm21 1H NMR (400
;
MHz, CDCl3): d = 1.84 (s, 3H, CH3), 3.87–3.90 (m, 4H,
NCH2CH2N), 7.18–7.22 (m, 1H, ArH), 7.42–7.55 (m, 7H, ArH),
7.63 (s, 1H, CH), 7.89–7.92 (m, 2H, ArH), 11.34 (br, 2H, NH);
13C NMR (100 MHz, CDCl3): d = 13.2 (CH3), 43.8 (NCH2), 43.8
(CH2N), 101.5, 106.5, 120.4, 125.0, 128.3, 128.7, 128.7, 130.9,
Fig. 3 X-ray crystal structures of 6c; ellipsoids are drawn at the 30% probability
level.
Scheme 3 Proposed mechanism for the three-component reaction.
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HRMS (EI): m/z calcd for C22H19ClN4O2 [M], 406.1197; found,
406.1191.
7.24–7.28 (m, 1H, ArH), 7.41–7.47 (m, 4H, ArH), 7.52–7.56 (m,
3H, ArH), 7.82 (s, 1H, CH), 7.87–7.89 (m, 2H, ArH), 11.19 (br,
2H, NH); 13C NMR (100 MHz, CDCl3): d = 43.9 (NCH2), 43.9
(CH2N), 100.2, 105.0, 119.1, 121.3, 121.8, 126.1, 128.4, 128.8,
128.9, 131.6, 138.4, 139.6, 147.8, 163.5 (HNCL), 165.3 (NCLO);
HRMS (EI): m/z calcd for C22H17F3N4O2 [M], 426.1304; found,
426.1296.
(Z)-4-(3-(4-Fluorophenyl)-2-(imidazolidin-2-ylidene)-3-oxo-
propylidene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6e).
Saffron yellow solid; m.p. 202–204 uC; IR (KBr): 3333, 2900,
1626, 1591, 1496, 1429, 1395, 1338, 1254, 1127, 1044, 993, 841,
765 cm21; 1H NMR (400 MHz, DMSO-d6): d = 1.97 (s, 3H, CH3),
3.74–3.78 (m, 4H, NCH2CH2N), 6.99–7.03 (m, 1H, ArH), 7.19–
7.24 (m, 2H, ArH), 7.27–7.31 (m, 2H, ArH), 7.41 (s, 1H, CH),
7.57–7.61 (m, 2H, ArH), 7.84–7.86 (m, 2H, ArH), 9.49 (br, 2H,
NH); 13C NMR (100 MHz, DMSO-d6): d = 13.1 (CH3), 43.4
(NCH2), 43.4 (CH2N), 105.1, 114.8 (d, J = 21.5 Hz), 117.8, 123.0,
128.5, 131.0, 137.1, 139.8, 142.9, 150.3, 162.1, 162.7 (HNCL),
164.5, 165.8 (NCLO), 191.0 (CLO); HRMS (EI): m/z calcd for
C22H19FN4O2 [M], 390.1492; found, 390.1492.
(Z)-4-(3-(4-Chlorophenyl)-2-(imidazolidin-2-ylidene)-3-oxo-
propylidene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-
one (6j). Saffron yellow solid; m.p. 230–233 uC; IR (KBr): 3221,
2969, 1640, 1583, 1499, 1403, 1282, 1176, 1114, 982, 836, 757
cm21 1H NMR (400 MHz, DMSO-d6): d = 3.80–3.87 (m, 4H,
;
NCH2CH2N), 7.14 (m, 1H, ArH), 7.37 (m, 3H, ArH), 7.54 (m,
4H, CH and ArH), 7.89 (m, 2H, ArH), 9.59 (br, 2H, NH); 13C
NMR (100 MHz, DMSO-d6): d = 43.7 (NCH2), 43.7 (CH2N),
106.3, 118.9, 120.0, 122.7, 124.4, 125.4, 128.4, 128.7, 130.2,
135.9, 137.9, 139.3, 141.1, 161.7 (HNCL), 166.3 (NCLO), 190.3
(CLO); HRMS (EI): m/z calcd for C22H16ClF3N4O2 [M], 460.0914;
found, 460.0915.
(Z)-4-(3-(2-Chlorophenyl)-2-(imidazolidin-2-ylidene)-3-oxo-
propylidene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (6f).
Saffron yellow solid; m.p. 204–207 uC; IR (KBr): 3278, 1886,
1625, 1588, 1497, 1434, 1282, 1243, 1133, 1042, 996, 759 cm21
;
1H NMR (400 MHz, DMSO-d6): d = 1.69 (s, 3H, CH3), 3.80–3.83
(m, 4H, NCH2CH2N), 7.04–7.08 (m, 2H, ArH), 7.31–7.35 (m,
3H, CH and ArH), 7.41–7.48 (m, 2H, ArH), 7.53–7.55 (m, 1H,
ArH), 7.88–7.89 (m, 2H, ArH), 10.09 (br, 2H, NH); 13C NMR
(100 MHz, DMSO-d6): d = 12.6 (CH3), 43.4 (NCH2), 43.4 (CH2N),
101.4, 105.2, 118.3, 123.6, 127.4, 128.6, 128.6, 129.4, 129.5,
130.6, 139.4, 139.9, 144.6, 150.7, 162.7 (HNCL), 164.3 (NCLO),
190.9 (CLO); HRMS (EI): m/z calcd for C22H19ClN4O2 [M],
406.1197; found, 406.1191.
(Z)-4-(2-(Imidazolidin-2-ylidene)-3-(4-methoxyphenyl)-3-oxo-
propylidene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-(4H)-
one (6g). Saffron yellow solid; m.p. 227–230 uC; IR (KBr): 3205,
2965, 1640, 1594, 1500, 1414, 1285, 1112, 1033, 982, 837, 761
cm21; 1H NMR (400 MHz, CDCl3): d = 3.87 (s, 3H, OCH3), 3.90–
3.94 (m, 4H, NCH2CH2N), 6.92–6.95 (m, 2H, ArH), 7.24–7.27
(m, 1H, ArH), 7.42–7.46 (m, 2H, ArH), 7.59–7.62 (m, 2H, ArH),
7.81 (s, 1H, CH), 7.89–7.91 (m, 2H, ArH), 11.18 (br, 2H, NH);
13C NMR (100 MHz, CDCl3): d = 44.0 (NCH2), 44.0 (CH2N), 55.5
(OCH3), 99.6, 105.3, 113.6, 119.5, 121.3, 126.0, 128.8, 128.8,
131.7, 131.9, 131.9, 138.5, 146.9, 162.9 (HNCL), 165.5 (NCLO),
197.1 (CLO); HRMS (EI): m/z calcd for C23H19F3N4O3 [M],
456.1409; found, 456.1407.
(Z)-4-(3-(4-Fluorophenyl)-2-(imidazolidin-2-ylidene)-3-oxo-
propylidene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-
one (6k). Saffron yellow solid; m.p. 237–240 uC; IR (KBr): 3305,
2900, 1633, 1606, 1523, 1500, 1442, 1377, 1274, 1236, 1184,
1123, 1044, 972, 841, 765 cm21; 1H NMR (400 MHz, DMSO-d6):
d = 3.82–3.87 (m, 4H, NCH2CH2N), 7.12–7.14 (m, 1H, ArH),
7.28–7.40 (m, 5H, CH and ArH), 7.57–7.62 (m, 2H, ArH), 7.88–
7.94 (m, 2H, ArH), 9.61 (br, 2H, NH); 13C NMR (100 MHz,
DMSO-d6): d = 43.7 (NCH2), 43.7 (CH2N), 96.7, 106.5, 115.3 (d, J
= 23.6 Hz), 118.9, 120.1, 122.8, 124.4, 128.7, 131.1, 135.7, 139.4,
141.1, 161.7, 162 (HNCL).4, 166.5 (NCLO), 190.4 (CLO); HRMS
(EI): m/z calcd for C22H16F4N4O2 [M], 444.1209; found,
444.1212.
(Z)-4-(3-(2-Chlorophenyl)-2-(imidazolidin-2-ylidene)-3-oxo-
propylidene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-
one (6l). Saffron yellow solid; m.p. 224–226 uC; IR (KBr): 3316,
2893, 1633, 1591, 1431, 1377, 1289, 1249, 1184, 1114, 1044,
1
971, 826, 757 cm21; H NMR (400 MHz, DMSO-d6): d = 3.86–
3.90 (m, 4H, NCH2CH2N), 7.10 (s, 1H, CH), 7.11–7.15 (m, 1H,
ArH), 7.32–7.40 (m, 3H, ArH), 7.44–7.49 (m, 2H, ArH), 7.54–
7.56 (m, 1H, ArH), 7.87–7.89 (m, 2H, ArH), 9.64 (br, 2H, NH);
13C NMR (100 MHz, DMSO-d6): d = 43.7 (NCH2), 43.7 (CH2N),
97.2, 106.9, 119.0, 119.8, 122.5, 124.5, 127.3, 128.6, 128.7,
129.6, 130.9, 138.8, 139.3, 142.2, 161.7 (HNCL), 165.2 (NCLO),
190.1 (CLO); HRMS (EI): m/z calcd for C22H16ClF3N4O2 [M],
460.0914; found, 460.0912.
(Z)-4-(2-(Imidazolidin-2-ylidene)-3-oxo-3-p-tolylpropylid-
ene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one (6h).
Saffron yellow solid; m.p. 207–209 uC; IR (KBr): 3292, 1889,
1634, 1531, 1499, 1441, 1376, 1278, 1180, 1122, 1040, 972, 766
1
cm21; H NMR (400 MHz, CDCl3): d = 2.42 (s, 3H, CH3), 3.90–
(Z)-4-(2-(1H-benzo[d]imidazol-2(3H,3aH,4H,5H,6H,7H,7a-
H)-ylidene)-3-(4-methoxyphenyl)-3-oxopropylidene)-3-methyl -
1-phenyl-1H-pyrazol-5(4H)-one (6m). Saffron yellow solid;
m.p. 206–207.5 uC; IR (KBr): 3264, 2933, 1617, 1583, 1500,
3.94 (m, 4H, NCH2CH2N), 7.23–7.27 (m, 3H, ArH), 7.41–7.49
(m, 4H, ArH), 7.83 (s, 1H, CH), 7.88–7.89 (m, 2H, ArH), 11.18
(br, 2H, NH); 13C NMR (100 MHz, CDCl3): d = 21.6 (PhCH3),
44.0 (NCH2), 44.0 (CH2N), 99.9, 105.3, 119.2, 121.3, 121.9,
126.1, 128.8, 129.0, 129.4, 136.6, 138.4, 142.6, 147.5, 163.0
(HNCL), 165.4 (NCLO), 198.3 (CLO); HRMS (EI): m/z calcd for
C23H19F3N4O2 [M], 440.1460; found, 440.1452.
1
1444, 1388, 1349, 1257, 1171, 1138, 1095, 779 cm21; H NMR
(400 MHz, DMSO-d6): d = 1.27–1.30 (m, 2H, CH2), 1.45–1.49 (m,
2H, CH2), 1.71–1.75 (m, 2H, CH2), 2.06–2.11 (m, 2H, CH2), 2.28
(s, 3H, CH3), 3.42–3.46 (m, 2H, NCHCHN), 3.82 (s, 3H, OCH3),
6.96–6.99 (m, 2H, ArH), 7.22–7.26 (m, 1H, ArH), 7.39–7.47 (m,
4H, ArH), 7.51 (s, 1H, CH), 7.67–7.69 (m, 2H, ArH), 9.99 (br,
2H, NH); 13C NMR (100 MHz, DMSO-d6): d = 11.2 (CH3), 23.4
(NCHCH2CH2), 23.4 (CH2CH2CHN), 28.3 (NCHCH2, 28.3
(CH2CHN), 55.5 (NCH), 55.5 (CHN), 64.1, 100.9, 113.7, 120.5,
(Z)-4-(2-(Imidazolidin-2-ylidene)-3-oxo-3-phenylpropylid-
ene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one (6i).
Saffron yellow solid; m.p. 233–235 uC; IR (KBr): 3288, 2886,
1632, 1523, 1499, 1437, 1370, 1272, 1183, 1121, 968, 758 cm21
;
1H NMR (400 MHz, CDCl3): d = 3.91–3.95 (m, 4H, NCH2CH2N),
13188 | RSC Adv., 2013, 3, 13183–13192
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121.4, 126.2, 129.1, 129.3, 130.3, 131.5, 135.4, 150.4, 158.5,
162.8 (HNCL), 166.9 (NCLO), 190.5 (CLO); HRMS (EI): m/z
calcd for C27H28N4O3 [M], 456.2161; found, 456.2157.
149.6, 161.2 (HNCL), 162.8 (NCLO), 190.3 (CLO); HRMS (EI):
m/z calcd for C23H22N4O2 [M], 386.1743; found, 386.1742.
(Z)-4-(3-(4-Chlorophenyl)-3-oxo-2-(tetrahydropyrimidin-2-
(1H)-ylidene)propylidene)-3-methyl-1-phenyl-1H-pyrazol-5-
(4H)-one (7d). Saffron yellow solid; m.p. 265–269 uC; IR (KBr):
3270, 2973, 1634, 1497, 1359, 1271, 1200, 1146, 1088, 997, 834,
747 cm21; 1H NMR (400 MHz, DMSO-d6): d = 1.94–1.98 (m, 5H,
CH3 and CH2), 3.30–3.37 (m, 4H, NCH2CH2N), 6.96–7.00 (m,
1H, ArH), 7.21 (s, 1H, CH), 7.27–7.31 (m, 2H, ArH), 7.48–7.54
(m, 4H, ArH), 7.98–7.99 (m, 2H, ArH), 9.05 (br, 2H, NH); 13C
NMR (100 MHz, DMSO-d6): d = 13.2 (CH3), 17.4 (CH2), 37.8
(NCH2), 37.8 (CH2N), 101.7, 108.9, 117.3, 122.2, 128.1, 128.4,
129.9, 134.7, 139.5, 140.5, 141,0, 149.8, 161.1 (HNCL), 162.8
(NCLO), 188.6 (CLO); HRMS (EI): m/z calcd for C23H21ClN4O2
[M], 420.1353; found, 420.1354.
(Z)-4-(2-(1H-benzo[d]imidazol-2(3H,3aH,4H,5H,6H,7H,7a-
H)-ylidene)-3-(2-chlorophenyl)-3-oxopropylidene)-3-methyl-1-
phenyl-1H-pyrazol-5(4H)-one (6n). Saffron yellow solid; m.p.
204–207.5 uC; IR (KBr): 3283, 2933, 1624, 1583, 1537, 1494,
1437, 1396, 1367, 1277, 1137, 756 cm21 1H NMR (400 MHz,
;
DMSO-d6): d = 1.31–1.34 (m, 2H, CH2), 1.38–1.39 (m, 2H, CH2),
1.57 (m, 2H, CH2), 1.69 (s, 3H, CH3), 1.73 (m, 2H, CH2), 4.11
(m, 2H, NCHCHN), 7.04–7.09 (m, 2H, ArH), 7.31–7.36 (m, 2H,
ArH), 7.38 (s, 1H, CH), 7.41–7.47 (m, 2H, ArH), 7.52–7.54 (m,
1H, ArH), 7.86–7.88 (m, 2H, ArH), 10.06 (br, 2H, NH); 13C NMR
(100 MHz, DMSO-d6): d = 12.6 (CH3), 19.3 (NCHCH2CH2), 19.3
(CH2CH2CHN), 25.8 (NCHCH2), 25.8 (CH2CHN), 54.3 (NCH),
54.3 (CHN), 101.6, 105.4, 118.2, 123.6, 127.4, 128.6, 128.7,
129.4, 129.5, 130.5, 139.4, 140.0, 144.1, 150.7, 162.7 (HNCL),
164.2 (NCLO), 191.0 (CLO); HRMS (EI): m/z calcd for
C26H25ClN4O2 [M], 460.1666; found, 460.1679.
(Z)-4-(3-(4-Fluorophenyl)-3-oxo-2-(tetrahydropyrimidin-2-
(1H)-ylidene)propylidene)-3-methyl-1-phenyl-1H-pyrazol-5-
(4H)-one (7e). Saffron yellow solid; m.p. 263–266 uC; IR (KBr):
3266, 2969, 1635, 1598, 1497, 1359, 1268, 1147, 1073, 997, 845,
754 cm21; 1H NMR (400 MHz, DMSO-d6): d = 1.93–1.96 (m, 5H,
CH2 and CH3), 3.28–3.34 (m, 4H, NCH2CH2N), 6.96–7.00 (m,
2H, ArH), 7.20 (s, 1H, CH), 7.26–7.31 (m, 4H, ArH), 7.53–7.56
(m, 2H, ArH), 7.96–7.98 (m, 2H, ArH), 9.03 (br, 2H, NH); 13C
NMR (100 MHz, DMSO-d6): d = 13.1 (CH3), 17.4 (CH2), 37.8
(NCH2), 37.8 (CH2N), 101.4, 109.1, 114.9 (d, J = 21.5 Hz), 117.4,
122.3, 128.4, 130.5, 137.1, 140.4, 141.1, 149.8, 161.1 (HNCL),
162.8 (NCLO), 163.0 (d, J = 245.9 Hz), 188.9 (CLO); HRMS (EI):
m/z calcd for C23H21FN4O2 [M], 404.1649; found, 404.1641.
(Z)-4-(3-(2-Chlorophenyl)-3-oxo-2-(tetrahydropyrimidin-2-
(1H) -ylidene)propylidene)-3-methyl-1-phenyl-1H-pyrazol-
5(4H)-one (7f). Saffron yellow solid; m.p. 252–254.5 uC; IR
(KBr): 3299, 2969, 1634, 1584, 1502, 1436, 1356, 1283, 1200,
(Z)-4-(3-(4-Methoxyphenyl)-3-oxo-2-(tetrahydropyrimidin-2-
(1H)-ylidene)propylidene)-3-methyl-1-phenyl-1H-pyrazol-5-
(4H)-one (7a). Saffron yellow solid; m.p. 224–229 uC; IR (KBr):
3263, 2962, 1635, 1597, 1500, 1461, 1359, 1309, 1265, 1166,
1
1030, 997, 837, 754 cm21; H NMR (500 MHz, DMSO-d6): d =
1.99 (s, 3H, CH3), 1.97–2.06 (m, 2H, CH2), 3.39–3.43 (m, 4H,
NCH2CH2N), 3.84 (s, 3H, OCH3), 6.99–7.04 (m, 3H, ArH), 7.27
(s, 1H, CH), 7.31–7.34 (m, 2H, ArH), 7.53–7.55 (m, 2H, ArH),
8.03–8.04 (m, 2H, ArH), 9.03 (br, 2H, NH); 13C NMR (125 MHz,
DMSO-d6): d = 13.6 (CH3), 17.8 (CH2), 38.2 (NCH2), 38.2
(CH2N), 55.7 (OCH3), 101.1, 109.9, 113.6, 117.7, 122.4, 128.7,
130.7, 133.2, 141.0, 141.3, 150.0, 161.3, 161.8 (HNCL), 163.3
(NCLO), 189.8 (CLO); HRMS (EI): m/z calcd for C24H24N4O3
[M], 416.1848; found, 416.1855.
1
1149, 1088, 993, 750 cm21; H NMR (500 MHz, DMSO-d6): d =
(Z)-3-Methyl-4-(3-oxo-2-(tetrahydropyrimidin-2(1H)-ylid-ene)-
3-p-tolylpropylidene)-1-phenyl-1H-pyrazol-5(4H)-one (7b).
Saffron yellow solid; m.p. 249–252 uC; IR (KBr): 3266, 2958,
1635, 1502, 1439, 1352, 1274, 1204, 1142, 1069, 997, 794, 754
1.83 (s, 3H, CH3), 1.98–2.04 (m, 2H, CH2), 3.36–3.44 (m, 4H,
NCH2CH2N), 6.88 (s, 1H, ACH), 6.99–7.03 (m, 1H, ArH), 7.31–
7.36 (m, 3H, ArH), 7.42–7.47 (m, 2H, CH and ArH), 7.53–7.54
(m, 1H, ArH), 8.00–8.02 (m, 2H, ArH), 9.05 (br, 2H, NH); 13C
NMR (125 MHz, DMSO-d6): d = 13.1 (CH3), 17.8 (CH2), 38.3
(NCH2), 38.3 (CH2N), 102.1, 109.9, 117.7, 122.7, 127.2, 128.7,
129.3, 129.8, 130.1, 130.5, 140.5, 140.8, 141.8, 149.7, 160.5
(HNCL), 163.2 (NCLO), 188.6 (CLO); HRMS (EI): m/z calcd for
C23H21ClN4O2 [M], 420.1353; found, 420.1348.
cm21 1H NMR (400 MHz, DMSO-d6): d = 1.93 (s, 3H, CH3),
;
1.96–1.98 (m, 2H, CH2), 2.35 (s, 3H, ArCH3), 3.29–3.33 (m, 4H,
NCH2CH2N), 6.96–6.99 (m, 1H, ArH), 7.22–7.31 (m, 5H, CH
and ArH), 7.39–7.42 (m, 2H, ArH), 7.96–7.98 (m, 2H, ArH), 9.00
(br, 2H, NH); 13C NMR (100 MHz, DMSO-d6): d = 13.2 (CH3),
17.4 (CH2), 21.1 (PhCH3), 37.8 (NCH2), 37.8 (CH2N), 100.9,
109.6, 117.4, 122.2, 128.4, 128.4, 128.5, 137.7, 140.2, 140.5,
141.2, 149.7, 161.2 (HNCL), 162.8 (NCLO), 190.3 (CLO); HRMS
(EI): m/z calcd for C24H24N4O2 [M], 400.1899; found, 400.1906.
(Z)-3-Methyl-4-(3-oxo-3-phenyl-2-(tetrahydropyrimidin-2-
(1H)-ylidene)propylidene)-1-phenyl-1H-pyrazol-5(4H)-one (7c).
Saffron yellow solid; m.p. 257–262 uC; IR (KBr): 3256, 3016,
1632, 1594, 1500, 1442, 1381, 1310, 1269, 1204, 1138, 1066,
990, 946, 758 cm21; 1H NMR (400 MHz, DMSO-d6): d = 1.92 (s,
3H, CH3), 1.95–1.98 (m, 2H, CH2), 3.30–3.36 (m, 4H,
NCH2CH2N), 6.96–6.99 (m, 1H, ArH), 7.21 (s, 1H, CH), 7.27–
7.31 (m, 2H, ArH), 7.43–7.49 (m, 5H, ArH), 7.98–8.00 (m, 2H,
ArH), 9.04 (br, 2H, NH); 13C NMR (100 MHz, DMSO-d6): d =
13.1 (CH3), 17.4 (CH2), 37.8 (NCH2), 37.8 (CH2N), 101.1, 109.4,
117.3, 122.2, 127.9, 128.0, 128.4, 130.1, 140.6, 140.7, 141.2,
(Z)-4-(3-(4-Methoxyphenyl)-3-oxo-2-(tetrahydropyrimidin-2-
(1H)-ylidene)propylidene)-1-phenyl-3-(trifluoromethyl)-
1H-pyrazol-5(4H)-one (7g). Saffron yellow solid; m.p. 291–293
uC; IR (KBr): 3278, 2965, 1641, 1595, 1501, 1465, 1292, 1258,
1172, 1113, 1069, 975, 838, 761 cm21 1H NMR (400 MHz,
;
DMSO-d6): d = 1.99–2.01 (m, 2H, CH2), 3.33–3.37 (m, 4H,
NCH2CH2N), 3.81 (s, 3H, OCH3), 7.01–7.03 (m, 2H, ArH), 7.11–
7.14 (m, 1H, ArH), 7.33–7.37 (m, 2H, ArH), 7.39 (s, 1H, CH),
7.52–7.54 (m, 2H, ArH), 7.94–7.96 (m, 2H, ArH), 9.19 (br, 2H,
NH); 13C NMR (100 MHz, DMSO-d6): d = 17.3 (CH2), 37.8
(NCH2), 37.8 (CH2N), 55.4 (OCH3), 95.0, 113.4, 114.3, 118.8,
121.6 (d, J = 268.7 Hz), 124.1, 128.7, 130.7, 139.0, 139.2, 139.6,
139.7, 160.3, 161.5 (HNCL), 161.8 (NCLO), 190.9 (CLO); HRMS
(EI): m/z calcd for
C
24H21F3N4O3 [M], 470.1566; found,
470.1566.
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(Z)-4-(3-Oxo-2-(tetrahydropyrimidin-2(1H)-ylidene)-3-p-tolyl-
RSC Advances
1037, 979 cm21; H NMR (400 MHz, DMSO-d6): d = 1.97–2.02
(m, 2H, CH2), 3.35–3.39 (m, 4H, NCH2CH2N), 6.97–7.00 (s, 1H,
CH), 7.13–7.15 (m, 1H, ArH), 7.32–7.39 (m, 3H, ArH), 7.43–7.49
(m, 2H, ArH), 7.52–7.54 (m, 1H, ArH), 7.89–7.92 (m, 2H, ArH),
9.23 (br, 2H, NH); 13C NMR (100 MHz, DMSO-d6): d = 17.3
(CH2), 37.8 (NCH2), 37.8 (CH2N), 95.8, 114.3, 118.8, 119.9,
122.6, 124.3, 127.0, 128.7, 129.5, 129.7, 130.7, 138.9, 139.5,
139.6, 140.6, 159.1 (HNCL), 161.8 (NCLO), 190.2 (CLO); HRMS
(EI): m/z calcd for C23H18ClF3N4O2 [M], 474.1070; found,
474.1078.
1
propylidene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-
one (7h). Saffron yellow solid; m.p. 296–298 uC; IR (KBr): 3299,
3013, 1640, 1595, 1499, 1454, 1288, 1179, 1115, 1066, 979, 830,
750 cm21; 1H NMR (400 MHz, DMSO-d6): d = 1.97–2.01 (m, 2H,
CH2), 2.36 (s, 3H, ArCH3), 3.33–3.37 (m, 4H, NCH2CH2N), 7.11–
7.14 (m, 1H, ArH), 7.27–7.29 (m, 2H, ArH), 7.34–7.38 (m, 2H,
ArH), 7.39 (s, 1H, ArH), 7.43–7.45 (m, 2H, ArH), 7.94–7.96 (m,
2H, ArH), 9.21 (br, 2H, NH); 13C NMR (100 MHz, DMSO-d6): d =
17.3 (CH2), 21.1 (PhCH3), 37.8 (NCH2), 37.8 (CH2N), 95.1,
114.2, 118.8, 120.2, 122.9, 124.1, 128.5, 128.7, 136.5, 139.3,
139.4, 139.6, 140.9, 160.2 (HNCL), 161.8 (NCLO), 191.7 (CLO);
HRMS (EI): m/z calcd for C24H21F3N4O2 [M], 454.1617; found,
454.1613.
(Z)-4-(3-Oxo-3-phenyl-2-(tetrahydropyrimidin-2(1H)-ylid-
ene)-propylidene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-
(4H)-one (7i). Saffron yellow solid; m.p. 276–285 uC; IR (KBr):
3297, 3013, 1640, 1591, 1500, 1288, 1182, 1118, 1073, 986, 834,
696 cm21; 1H NMR (400 MHz, DMSO-d6): d = 1.97–2.01 (m, 2H,
CH2), 3.33–3.37 (m, 4H, NCH2CH2N), 7.11–7.15 (m, 1H, ArH),
7.32 (s, 1H, CH), 7.36–7.39 (m, 2H, ArH), 7.45–7.55 (m, 5H,
ArH), 7.93–7.95 (m, 2H, ArH), 9.23 (br, 2H, NH); 13C NMR (100
MHz, DMSO-d6): d = 17.3 (CH2), 37.8 (NCH2), 37.8 (CH2N),
95.3, 114.1, 118.8, 120.2, 122.9, 124.2, 128.1, 128.2, 128.7,
130.8, 139.3, 139.4, 139.7, 160.1 (HNCL), 161.8 (NCLO), 192.0
(CLO); HRMS (EI+): m/z calcd for C23H19F3N4O2 [M], 440.1460;
found, 440.1457.
(Z)-4-(3-(4-Chlorophenyl)-3-oxo-2-(tetrahydropyrimidin-2-
(1H) -ylidene)propylidene)-1-phenyl-3-(trifluoromethyl)-
1H-pyr-azol-5(4H)-one (7j). Saffron yellow solid; m.p. . 300
uC; IR (KBr): 3027, 2581, 1640, 1600, 1499, 1465, 1398, 1291,
1181, 1116, 982, 834, 756 cm21; 1H NMR (400 MHz, DMSO-d6):
d = 1.96–1.98 (m, 2H, CH2), 3.32–3.35 (m, 4H, NCH2CH2N),
7.11–7.15 (m, 1H, ArH), 7.29 (s, 1H, CH), 7.38–7.39 (m, 2H,
ArH), 7.50–7.57 (m, 4H, ArH), 7.91–7.93 (m, 2H, ArH), 9.24 (br,
2H, NH); 13C NMR (100 MHz, DMSO-d6): d = 17.2 (CH2), 37.8
(NCH2), 37.8 (CH2N), 95.6, 113.6, 118.8, 121.5, 123.0, 124.2,
128.3, 128.7, 130.0, 135.5, 138.2, 139.6, 159.9 (HNCL), 161.7
(NCLO), 190.5 (CLO); HRMS (EI): m/z calcd for C23H18ClF3N4O2
[M], 474.1070; found, 474.1073.
(Z)-4-(3-Oxo-2-(tetrahydropyrimidin-2(1H)-ylidene)-3-p-tolyl-
propylidene)-1-(2,4,6-trichlorophenyl)-3-(trifluorometh-yl)-
1H-pyrazol-5(4H)-one (7m). Saffron yellow solid; m.p. 286–289
uC; IR (KBr): 3279, 2918, 1633, 1591, 1498, 1345, 1272, 1142,
1091, 993, 747 cm21; H NMR (400 MHz, DMSO-d6): d = 1.86–
1
1.90 (m, 2H, CH2), 2.36 (s, 3H, ArCH3), 3.26–3.35 (m, 4H,
NCH2CH2N), 7.27–7.29 (m, 2H, ArH), 7.35 (s, 1H, CH), 7.42–
7.44 (m, 2H, ArH), 7.84 (m, 2H, ArH), 9.23 (br, 2H, NH); 13C
NMR (100 MHz, DMSO-d6): d = 17.3 (CH2), 21.1 (PhCH3), 37.6
(NCH2), 37.6 (CH2N), 93.3, 114.4, 121.4 (d, J = 268.8 Hz), 122.7,
128.4, 128.6, 133.9, 134.5, 135.8, 136.5, 139.6, 140.4, 140.8,
160.0 (HNCL), 161.8 (NCLO), 191.3 (CLO); HRMS (TOF ES+): m/
z calcd for C24H18Cl3F3N4O2 [(M + H)+], 557.0520; found,
557.0519.
(Z)-4-(2-(1,3-Diazepan-2-ylidene)-3-(4-methoxyphenyl)-3-oxo-
propylidene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (8a).
Saffron yellow solid; m.p. 244–248.5 uC; IR (KBr): 3280, 2924,
1634, 1595, 1501, 1349, 1268, 1162, 1138, 1033, 993, 801, 755
cm21 1H NMR (400 MHz, DMSO-d6): d = 1.74–1.78 (m, 4H,
;
NCH2CH2N), 1.97 (s, 3H, CH3), 3.33–3.36 (m, 4H, NCH2CH2N),
3.78 (s, 3H, OCH3), 6.97–6.99 (m, 3H, CH and ArH), 7.25–7.31
(m, 3H, ArH), 7.47–7.49 (m, 2H, ArH), 7.94–7.96 (m, 2H, ArH),
8.81 (br, 2H, NH); 13C NMR (100 MHz, DMSO-d6): d = 13.3
(CH3), 26.3 (CH2CH2), 26.3 (CH2CH2), 43.5 (NCH2), 43.5
(CH2N), 55.3 (OCH3), 101.6, 110.9, 113.2, 117.4, 122.4, 128.4,
130.2, 133.1, 140.4, 141.5, 149.9, 160.9 (HNCL), 162.9 (NCLO),
167.3 (CH3OC), 190.4 (CLO); HRMS (EI): m/z calcd for
C25H26N4O3 [M], 430.2005; found, 430.2000.
(Z)-4-(2-(1,3-Diazepan-2-ylidene)-3-oxo-3-p-tolylpropylid-
ene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (8b). Saffron yel-
low solid; m.p. 263–265 uC; IR (KBr): 3281, 2922, 1633, 1499,
(Z)-4-(3-(4-Fluorophenyl)-3-oxo-2-(tetrahydropyrimidin-2-
(1H)-ylidene)propylidene)-1-phenyl-3-(trifluoromethyl)-1H-pyr-
azol-5(4H)-one (7k). Saffron yellow solid; m.p. 284–288.5 uC; IR
(KBr): 3263, 3016, 1641, 1595, 1500, 1457, 1399, 1290, 1174,
1352, 1273, 1142, 1001, 790, 750 cm21 1H NMR (400 MHz,
;
DMSO-d6): d = 1.82–1.87 (m, 4H, CH2CH2), 2.19 (s, 3H, CH3),
2.35 (s, 3H, ArCH3), 3.39–3.43 (m, 4H, NCH2CH2N), 7.21 (s, 1H,
CH), 7.27–7.37 (m, 3H, ArH), 7.46–7.49 (m, 3H, ArH), 7.54–7.57
(m, 3H, ArH), 9.27 (br, 2H, NH); 13C NMR (100 MHz, DMSO-
d6): d = 11.0 (CH3), 21.1 (PhCH3), 25.9 (CH2CH2), 25.9
(CH2CH2), 43.6 (NCH2), 43.6 (CH2N), 99.8, 120.6, 122.7,
126.4, 129.0, 129.1, 129.3, 135.0, 135.4, 139.0, 142.5, 150.6,
158.5 (HNCL), 164.0 (NCLO), 192.6 (CLO); HRMS (EI): m/z
calcd for C25H26N4O2 [M], 414.2056; found, 414.2053.
1
1116, 1069, 979, 754 cm21; H NMR (400 MHz, DMSO-d6): d =
1.97–2.02 (m, 2H, CH2), 3.33–3.36 (m, 4H, NCH2CH2N), 7.11–
7.15 (m, 1H, ArH), 7.27–7.31 (m, 2H, CH and ArH), 7.32–7.40
(m, 3H, ArH), 7.56–7.60 (m, 2H, ArH), 7.93–7.95 (m, 2H, ArH),
9.24 (br, 2H, NH); 13C NMR (100 MHz, DMSO-d6): d = 17.3
(CH2), 37.8 (NCH2), 37.8 (CH2N), 95.4, 113.8, 115.1, 115.3,
118.8, 121.5 (d, J = 268.7 Hz), 124.2, 128.7, 130.8, 130.9, 135.9,
139.6, 160.1 (HNCL), 161.8 (NCLO), 163.4 (d, J = 247.0 Hz),
190.6 (CLO); HRMS (EI): m/z calcd for C23H18F4N4O2 [M],
458.1366; found, 458.1356.
(Z)-4-(3-(2-Chlorophenyl)-3-oxo-2-(tetrahydropyrimidin-2-
(1H)-ylidene)propylidene)-1-phenyl-3-(trifluoromethyl)-1H-pyr-
azol-5(4H)-one (7l). Saffron yellow solid; m.p. 283–287 uC; IR
(KBr): 3322, 3009, 1641, 1594, 1541, 1504, 1297, 1185, 1119,
(Z)-4-(2-(1,3-Diazepan-2-ylidene)-3-oxo-3-phenylpropylid-
ene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (8c). Saffron yel-
low solid; m.p. 223–227 uC; IR (KBr): 3274, 2926, 1633, 1499,
1341, 1268, 1138, 997, 805, 750 cm21 1H NMR (400 MHz,
;
CDCl3): d = 1.86–1.93 (m, 4H, CH2CH2), 1.92 (s, 3H, CH3), 3.17
(m, 2H, NCH2), 3.49 (m, 2H, NCH2), 7.07–7.11 (m, 1H, ArH),
7.26 (s, 1H, CH), 7.31–7.39 (m, 4H, ArH), 7.43–7.46 (m, 1H,
13190 | RSC Adv., 2013, 3, 13183–13192
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ArH), 7.51–7.52 (m, 2H, ArH), 7.76–7.78 (m, 2H, ArH); 13C NMR
(100 MHz, CDCl3): d = 12.9 (CH3), 26.4 (CH2CH2), 26.4
(CH2CH2), 44.8 (NCH2), 44.8 (CH2N), 104.2, 109.5, 119.9,
124.5, 128.2, 128.6, 128.8, 131.2, 138.8, 140.1, 145.9, 151.5,
162.8 (HNCL), 166.6 (NCLO), 195.6 (CLO); HRMS (EI): m/z
calcd for C24H24N4O2 [M], 400.1899; found, 400.1908.
140.1, 141.0, 162.0, 162.3 (HNCL), 166.1 (NCLO), 192.5 (CLO);
HRMS (EI): m/z calcd for C25H23F3N4O2 [M], 468.1773; found,
468.1767.
(Z)-4-(2-(1,3-Diazepan-2-ylidene)-3-oxo-3-phenylpropylid-
ene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one (8h).
Saffron yellow solid; m.p. 267–272 uC; IR (KBr): 3305, 3023,
1640, 1537, 1499, 1396, 1286, 1178, 1116, 986, 827, 689 cm21
;
(Z)-4-(3-(4-Chlorophenyl)-2-(1,3-diazepan-2-ylidene)-3-oxo-
propylidene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (8d).
Saffron yellow solid; m.p. 275–279 uC; IR (KBr): 3279, 2918,
1H NMR (400 MHz, DMSO-d6): d = 1.81–1.85 (m, 4H,
NCH2CH2N), 3.39–3.50 (m, 4H, NCH2CH2N), 7.11–7.15 (m,
1H, ArH), 7.32 (s, 1H, CH), 7.36–7.39 (m, 3H, ArH), 7.45–7.54
(m, 4H, ArH), 7.93–7.95 (m, 2H, ArH), 9.08 (br, 2H, NH); 13C
NMR (100 MHz, DMSO-d6): d = 26.2 (CH2CH2), 26.2 (CH2CH2),
43.2 (NCH2), 43.2 (CH2N), 95.6, 115.6, 118.7, 120.2, 124.2,
128.0, 128.1, 128.7, 130.7, 139.5, 139.6, 139.7, 161.9 (HNCL),
165.5 (NCLO), 192.5 (CLO); HRMS (EI): m/z calcd for
1633, 1591, 1498, 1345, 1272, 1142, 1091, 933, 837, 747 cm21
;
1H NMR (400 MHz, DMSO-d6): d = 1.82–1.86 (m, 4H, CH2CH2),
2.21 (s, 3H, CH3), 3.40–3.45 (m, 4H, NCH2CH2N), 7.22 (s, 1H,
CH), 7.26–7.30 (m, 1H, ArH), 7.46–7.49 (m, 2H, ArH), 7.56–7.58
(m, 4H, ArH), 7.63–7.65 (m, 2H, ArH), 9.29 (br, 2H, NH); 13C
NMR (100 MHz, DMSO-d6): d = 11.1 (CH3), 25.8 (CH2CH2), 26.0
(CH2CH2), 43.6 (NCH2), 43.6 (CH2N), 99.9, 120.6, 121.9, 126.3,
128.6, 129.3, 130.7, 135.4, 136.6, 136.8, 139.6, 150.8, 158.6
(HNCL), 163.9 (NCLO), 191.7 (CLO); HRMS (EI): m/z calcd for
C24H23ClN4O2 [M], 434.1510; found, 434.1524.
C
24H21F3N4O2 [M], 454.1617; found, 454.1611.
(Z)-4-(3-(4-Chlorophenyl)-2-(1,3-diazepan-2-ylidene)-3-oxo-
propylidene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-
one (8i). Saffron yellow solid; m.p. 291–294 uC; IR (KBr): 3300,
3023, 1635, 1591, 1498, 1396, 1288, 1179, 1117, 986, 834, 750
(Z)-4-(3-(2-Chlorophenyl)-2-(1,3-diazepan-2-ylidene)-3-oxo -
propylidene)-3-methyl-1-phenyl-1H-pyrazol-5(4H)-one (8e).
Saffron yellow solid; m.p. 244–249 uC; IR (KBr): 3317, 2922,
cm21 1H NMR (400 MHz, DMSO-d6): d = 1.81–1.85 (m, 4H,
;
CH2CH2), 3.41–3.60 (m, 4H, NCH2CH2N), 7.11–7.15 (m, 1H,
ArH), 7.29 (s, 1H, CH), 7.36–7.39 (m, 2H, ArH), 7.49–7.52 (m,
2H, ArH), 7.54–7.57 (m, 2H, ArH), 7.90–7.94 (m, 2H, ArH), 9.09
(br, 2H, NH); 13C NMR (100 MHz, DMSO-d6): d = 26.2
(CH2CH2), 26.2 (CH2CH2), 43.2 (NCH2), 43.2 (CH2N), 95.9,
115.2, 118.8, 121.5 (d, J = 268.8 Hz), 124.3, 128.3, 128.7, 129.9,
135.4, 138.4, 139.3, 139.5, 139.7, 161.9, 165.3(HNCL), 165.3
(NCLO), 919.1 (CLO); HRMS (EI): m/z calcd for C24H20ClF3N4O2
[M], 488.1227; found, 488.1227.
1635, 1581, 1504, 1443, 1349, 1283, 1146, 1055, 993, 750 cm21
;
1H NMR (500 MHz, DMSO-d6): d = 1.76–1.96 (m, 7H, CH3 and
CH2CH2), 3.38–3.41 (m, 4H, NCH2CH2N), 6.99–7.02 (m, 1H,
ArH), 7.29–7.32 (m, 2H, ArH), 7.38 (s, 1H, CH), 7.41–7.42 (m,
3H, ArH), 7.49 (m, 1H, ArH), 7.98–7.99 (m, 2H, ArH), 8.83 (br,
2H, NH); 13C NMR (125 MHz, DMSO-d6): d = 13.2 (CH3), 26.4
(CH2CH2), 26.4 (CH2CH2), 43.4 (NCH2), 43.4 (CH2N), 102.7,
111.1, 117.7, 122.7, 127.1, 128.1, 128.7, 129.3, 129.7, 130.0,
130.4, 140.7, 141.4, 149.9, 163.3 (HNCL), 166.3 (NCLO), 188.7
(CLO); HRMS (EI): m/z calcd for C24H23ClN4O2 [M], 434.1510;
found, 434.1502.
(Z)-4-(3-(2-Chlorophenyl)-2-(1,3-diazepan-2-ylidene)-3-oxo -
propylidene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H) -
one (8j). Saffron yellow solid; m.p. 298–302 uC; IR (KBr):
3333, 2947, 1640, 1592, 1540, 1500, 1180, 1113, 982, 827, 758
(Z)-4-(2-(1,3-Diazepan-2-ylidene)-3-(4-methoxyphenyl)-3-oxo-
propylidene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5-(4H)-
one (8f). Saffron yellow solid; m.p. 288–290.5 uC; IR (KBr):
3305, 2926, 1635, 1595, 1500, 1396, 1289, 1262, 1173, 1115,
cm21 1H NMR (400 MHz, DMSO-d6): d = 1.80–1.90 (m, 4H,
;
CH2CH2), 3.50–3.55 (m, 4H, NCH2CH2N), 7.07 (s, 1H, CH),
7.11–7.15 (m, 1H, ArH), 7.36–7.48 (m, 5H, ArH), 7.51–7.53 (m,
1H, ArH), 7.90–7.92 (m, 2H, ArH), 9.04 (br, 2H, NH); 13C NMR
(100 MHz, DMSO-d6): d = 26.1 (CH2CH2), 26.1 (CH2CH2), 43.0
(NCH2), 43.0 (CH2N), 95.9, 106.5, 115.8, 118.8, 121.2 (d, J =
268.7 Hz), 124.3, 125.3, 126.9, 128.7, 128.8, 129.5, 129.6, 130.6,
139.1–140.0 (m), 139.3, 161.9 (HNCL), 164.4 (NCLO), 190.5
(CLO); HRMS (TOF ES+): m/z calcd for C24H20ClF3N4O2 [(M +
H)+], 489.1300; found, 489.1300.
1
1019, 982, 841, 754 cm21; H NMR (400 MHz, DMSO-d6): d =
1.85 (m, 4H, 2CH2), 3.44 (m, 4H, 2CH2), 3.79 (s, 3H, OCH3),
7.00–7.02 (m, 2H, ArH), 7.11–7.15 (m, 1H, ArH), 7.32 (s, 1H,
CH), 7.36–7.39 (m, 2H, ArH), 7.51–7.53 (m, 2H, ArH), 7.92–7.94
(m, 2H, ArH), 9.025 (s, 2H, NH); 13C NMR (100 MHz, DMSO-
d6): d = 26.2 (CH2CH2), 26.2 (CH2CH2), 43.2 (NCH2), 43.2
(CH2N), 55.4 (OCH3), 95.3, 113.4, 115.9, 118.8, 120.6 (d, J =
268.7 Hz), 124.2, 128.7, 130.6, 131.6, 139.1, 139.3, 139.7, 161.5,
161.9 (HNCL), 165.7 (NCLO), 191.6 (CLO); HRMS (EI): m/z
calcd for C25H23F3N4O3 [M], 484.1722; found, 484.1727.
Acknowledgements
(Z)-4-(2-(1,3-Diazepan-2-ylidene)-3-oxo-3-p-tolylpropylid-
ene)-1-phenyl-3-(trifluoromethyl)-1H-pyrazol-5(4H)-one (8g).
Saffron yellow solid; m.p. 298–300 uC; IR (KBr): 3300, 2929,
We gratefully acknowledge financial support from the Natural
Science Foundation of China (no. 81160384, 21162037,
21262042, U1202221) and the Natural Science Foundation of
Yunnan Province Education Department (2011Z042,
2012HB001 and 2010120303).
1636, 1498, 1396, 1285, 1178, 1115, 986, 834, 755 cm21 1H
;
NMR (500 MHz, DMSO-d6): d = 1.85–1.90 (m, 4H, CH2CH2),
2.38 (s, 3H, ArCH3), 3.42–3.48 (m, 4H, NCH2CH2N), 7.14–7.17
(m, 1H, ArH), 7.29–7.31 (m, 2H, ArH), 7.37–7.42 (m, 4H, CH
and ArH), 7.45–7.47 (m, 1H, ArH), 7.98–7.99 (m, 2H, ArH), 9.08
(br, 2H, NH); 13C NMR (125 MHz, DMSO-d6): d = 21.4 (CH3),
26.6 (CH2CH2), 26.6 (CH2CH2), 43.6 (NCH2), 43.6 (CH2N), 95.8,
116.1, 119.0, 120.9, 123.0, 124.4, 128.7, 128.9, 137.2, 139.6,
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13192 | RSC Adv., 2013, 3, 13183–13192
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