Combined inorganic base promoted N-addition/[2,3]-sigmatropic rearrangement to construct homoallyl sulfur-containing pyrazolones

Article abstract of DOI:10.1039/c9ra07610g

The first sequentially combined inorganic base promoted N-addition/[2,3]-sigmatropic rearrangement reaction of α-alkylidene pyrazolinones and propargyl sulfonium salts has been reported to construct homoallyl sulfur-containing pyrazolones with moderate to excellent yields. α-Alkylidene pyrazolinones function as N-nucleophilic agents distinguished from the reported C-addition reactions. Propargyl sulfonium salts were first involved in the [2,3]-sigmatropic rearrangement protocol differentiated from the well-established annulation reactions. The excellent regioselectivity, the broad scope of substrates, gram-scale synthesis and convenient transformation embody the synthetic superiority of this cascade process.

Full text of DOI:10.1039/c9ra07610g

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PAPER
Combined inorganic base promoted N-addition/
[2,3]-sigmatropic rearrangement to construct
homoallyl sulfur-containing pyrazolones†
Cite this: RSC Adv., 2019, 9, 34912
a
Xiao-Li Du,a Xiao-Li Xu,b Yue-Hua Wu,b Ming-gang Zhaoa
*
*
Shou-Jie Shen,
and Jin-Yan Liang
b
The first sequentially combined inorganic base promoted N-addition/[2,3]-sigmatropic rearrangement
reaction of a-alkylidene pyrazolinones and propargyl sulfonium salts has been reported to construct
homoallyl sulfur-containing pyrazolones with moderate to excellent yields. a-Alkylidene pyrazolinones
function as N-nucleophilic agents distinguished from the reported C-addition reactions. Propargyl
sulfonium salts were first involved in the [2,3]-sigmatropic rearrangement protocol differentiated from
the well-established annulation reactions. The excellent regioselectivity, the broad scope of substrates,
gram-scale synthesis and convenient transformation embody the synthetic superiority of this cascade
process.
Received 19th September 2019
Accepted 22nd October 2019
DOI: 10.1039/c9ra07610g
rsc.li/rsc-advances
Introduction
Organosulfur compounds that exist broadly in biologically
active natural products as well as pharmaceuticals and are
engaged in numerous chemical transformations, have been
attracting vivid interest from academia and industry.1 Sulfur
ylides are among the most versatile class of structural motifs,
having widespread applications ranging from classical cyclo-
propanation, epoxidation and aziridination to more compli-
cated [n
+
1]-cycloadditions, domino reactions and
rearrangement reactions based on transition metal catalysis,
organocatalysis and photocatalysis.2 As an efficient C–C bond-
forming strategy, [2,3]-sigmatropic rearrangements of sulfur
ylides have been widely explored and applied since their
discovery in the late 1960s.3,4 The transition metal carbenoid-
mediated rearrangement reactions between allyl suldes and
diazo species named Doyle–Kirmse reactions are representative
examples and have made impressive progress especially in to
the content of catalytic and asymmetric variants in the past
decade (Scheme 1a).5 Metal-free generation of sulfur ylides in
situ between allyl thioethers and arynes followed by [2,3]-
sigmatropic rearrangements are also alternative methods
(Scheme 1b).6 Despite the aforementioned excellent work, the
aKey Laboratory of Magnetic Molecules, Magnetic Information Materials Ministry of
Education, The School of Chemical and Material Science, Shanxi Normal University,
Linfen, 041004, China. E-mail: shoujie_shen@outlook.com; jinyan_liang@outlook.
com
bCollege of Life Science, Shanxi Normal University, Linfen, 041004, China
† Electronic supplementary information (ESI) available: Copies of 1H, 13C and 19
Scheme 1 [2,3]-Sigmatropic rearrangements of sulfur ylides (a and b)
and N-2 initiating nucleophilic reaction of a,b-unsaturated pyrazolone
(c).
F
NMR and ESI-HRMS spectra for compounds. CCDC 1943758. For ESI and
crystallographic data in CIF or other electronic format see DOI:
10.1039/c9ra07610g
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attempt to utilize propargyl sulfonium salts to form key species processive interests on constructing functionalized pyrazolones
of sulfur ylides accompanied by subsequent [2,3]-sigmatropic and exploring the diverse reactive pathway of propargyl sulfo-
rearrangements process has not been achieved.
Propargyl sulfonium salts, because of their easy acquire- NaOAc$3H2O/KOH-promoted
nium salts,9,15 we herein report the realization of regioselective
N-addition/[2,3]-sigmatropic
ments and multiple reaction sites, are versatile and promising rearrangement reaction of a-alkylidene pyrazolinones and
building blocks. Generally, propargyl sulfonium salts can propargyl sulfonium salts, delivering bioactive homoallyl
isomerize to allenic sulfonium salts in the presence of the base, sulfur-containing pyrazolones in moderate to excellent yields
which are active forms and possess three reactive sites of a- (Scheme 1d).
carbon, b-carbon and a0-carbon (Scheme 1c). Kanematsu's,7
Huang's8 and our group9 have reported the [n + 2] or [n + 1]
cascade annulation reactions based on a-carbon and b-carbon
Results and discussion
We began our investigation by selecting a-alkylidene pyr-
azolinone 1a and propargyl sulfonium salt 2a as model
substrates (Table 1). When 1a (0.2 mmol, 1.0 equiv.), 2a
(0.24 mmol, 1.2 equiv.) and NaOAc$3H2O (0.1 mmol, 0.5 equiv.)
in CH3CN (2 mL) were mixed and stirred for 10 minutes at 20 ꢀC,
the a-alkylidene pyrazolinone 1a was consumed completely.
Aer the reaction temperature was decreased to 0 ꢀC, KOH
(0.4 mmol, 2.0 equiv.) was added and the reaction was stirred
for 6 h at 0 ꢀC to afford N-addition/[2,3]-sigmatropic rear-
rangement product 3a with 82% yield (Table 1, entry 4). When
the mixture of NaOAc$3H2O and KOH was added in one
portion, a-alkylidene pyrazolinone could not be consumed
completely even aer 12 h and the operation caused decreased
yield. Extensive exploration of a range of bases indicated that
NaOAc$3H2O or anhydrous NaOAc was most efficient to
promote the process (entries 4–5 vs. 1–3 and 6–10 in Table 1).
The combined usage of bases NaOAc$3H2O and KOH was
sites. Meanwhile, pyrazolones represent a class of privileged
heterocycles that exhibit extensive physiological and pharma-
cological activities and are valuable drug candidates.10 Accord-
ingly, fruitful protocols have been explored to access versatile
pyrazolones architectures based on the multiple reactive sites of
pyrazolin-5-ones and a,b-unsaturated pyrazolones.11,12 As to a,b-
unsaturated pyrazolones having g-H, the preferential g-C
nucleophilic property facilities their functioning as C3 synthons
to construct spiro-pyrazolones by [3 + n] annulation.13 In
contrast, the N-2 initiating nucleophilic reaction of a,b-unsat-
urated pyrazolones was less investigated. Recently our group
reported the rst regioselective NaOAc$3H2O-promoted N-
addition/substitution reaction between a-alkylidene pyr-
azolinones and propargyl sulfonium salts (Scheme 1c).14 Acci-
dentally, we found that strong inorganic bases can efficiently
promoted the rearrangement of sulfur salts. Based on our
Table 1 Optimization of the reaction conditionsa
Entry
Base1/base2
Solvent
1a : 2a : base1 : base2
Yieldb (%)
1
2
3
4
5
6
7
8
Na2CO3/KOH
K2CO3/KOH
Cs2CO3/KOH
NaOAc$3H2O/KOH
NaOAc/KOH
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH2CI2
CHCI3
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 0
1 : 1.2 : 0 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 1.2 : 0.5 : 2
1 : 2.0 : 0.5 : 2
1 : 1.2 : 0.25 : 2
1 : 1.2 : 1.0 : 2
1 : 1.2 : 0.5 : 4
1 : 1.2 : 0.5 : 2
69
58
75
82
82
68
39
68
60
75
0
46
74
68
74
53
64
48
36
83
80
82
81
78
KOAc/KOH
NEt3/KOH
DABCOc/KOH
9
DBUd/KOH
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
DMAPe/KOH
NaOAc$3H2O
KOH
NaOAc$3H2O/NaOH
NaOAc$3H2O/LiOH
NaOAc$3H2O/KOH
NaOAc$3H2O/KOH
NaOAc$3H2O/KOH
NaOAc$3H2O/KOH
NaOAc$3H2O/KOH
NaOAc$3H2O/KOH
NaOAc$3H2O/KOH
NaOAc$3H2O/KOH
NaOAc$3H2O/KOH
NaOAc$3H2O/KOH
MeOH
THF
Toluene
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
a
Unless otherwise noted, the reactions were performed under air and a-alkylidene pyrazolinones 1 (0.2 mmol, 1.0 equiv.), sulfonium salt 2a
(0.24 mmol, 1.2 equiv.) and NaOAc$3H2O (0.1 mmol, 0.5 equiv.) in CH3CN (2.0 mL) were mixed and stirred for 10–40 minutes at 20 ꢀC until
starting material 1a disappeared (monitored by TLC), then the reaction temperature was decreased to 0 ꢀC and KOH (2.0 equiv.) was added to
keep stirring at 0 ꢀC for 6–10 h. b Isolated yield.
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Scheme 3 Scope of a-alkylidene pyrazolinones on the pyrazolinone
ring.a Unless otherwise noted, the reactions were performed under air
and a-alkylidene pyrazolinones 1 (0.2 mmol, 1.0 equiv.), sulfonium salt
2a (0.24 mmol, 1.2 equiv.) and NaOAc$3H2O (0.1 mmol, 0.5 equiv.) in
CH3CN (2.0 mL) were mixed and stirred for 10–40 minutes at 20 ꢀC
until starting material 1 disappeared (monitored by TLC), then the
reaction temperature was decreased to 0 ꢀC and KOH (2.0 equiv.) was
added to keep stirring at 0 ꢀC for 6–10 h. bIsolated yield.
Scheme 2 Scope of Disubstituted a-Alkylidene Pyrazolinones.a Unless
otherwise noted, the reactions were performed under air and a-
alkylidene pyrazolinones 1 (0.2 mmol, 1.0 equiv.), sulfonium salt 2a
(0.24 mmol, 1.2 equiv.) and NaOAc$3H2O (0.1 mmol, 0.5 equiv.) in
CH3CN (2.0 mL) were mixed, stirred for 10–40 minutes at 20 ꢀC until
starting material 1a disappeared (monitored by TLC), then the reaction
temperature was decreased to 0 ꢀC and KOH (2.0 equiv.) was added to
keep stirring at 0 ꢀC for 6–10 h.b Isolated yield.
transformation. Acetophenones derived alkylidene pyr-
azolinones 1 with methyl, methoxy, chloro-, bromo-, iodo-,
nitro- and cyano-groups on ortho-, meta- or para-positions,
crucial for the high efficiency while NaOAc$3H2O or KOH was could react effectively with propargyl sulfonium salt 2a to
utilized separately to give the desired 3a in 0% and 46% yields, furnish the related homoallyl sulfur-containing pyrazolones in
respectively (Table 1, entries 11–12). Replacement of KOH with 59–91% yields (3a–3n in Scheme 2). As to the same substituent
NaOH or LiOH gave related 74% and 68% yields (Table 1, on phenyl group, such as methyl, methoxy and chloro-, ortho-
entries 13–14). Screening of solvents including CH2Cl2, CHCl3, and meta-positions exhibited higher yields than para-position
MeOH, THF and toluene did not give a better yield (entries 4 vs. (3b vs. 3i, 3l; 3c vs. 3j, 3m; 3d vs. 3k, 3n). Naphthyl-substituted a-
15–19). We also probed the inuence of the amount of sulfo- alkylidene pyrazolinones were well-tolerated to provide 3o, 3p
nium salts 2a, NaOAc$3H2O and KOH. Increasing the content of and 3q in 66, 76 and 83% yields, respectively. Hetero-aromatic
propargyl sulfonium salt 2a to 2.0 equiv. has little inuence on unsaturated pyrazolinones containing thiophene and N-
yield (entry 20). Decreasing the amount of NaOAc$3H2O to 0.25 methyl protected pyrrole could participate in the reaction to
equiv. or increasing to 1.0 equiv. had a slight effect on yield afford corresponding product 3r and 3s in 57 and 70% yields,
(entries 21–22). Increasing the quantities of KOH to 4.0 equiv. respectively. Double alkyl-substituted alkylidene pyrazolinone
did not improve the yield (entry 23). The yield wasꢀdeclined from could also be engaged in the reaction to produce the predicted
82% to 78% when the reaction was stirred at 20 C (entry 24).
3t with 72% yield. In contrast, when the methyl group was
Having established the optimized conditions (Table 1, entry replaced by ethyl (R1 ¼ CH3) or benzyl groups (R1 ¼ Ph), the
4), we commenced to explore the substrate scope of the reaction desired reaction was sluggish, abundant alkylidene pyr-
(Scheme 2). Generally, the existence of methyl group (R1 ¼ H) at azolinones were recovered and no target products 3u or 3v could
a-position of alkylidene pyrazolinones was pivotal for the be separated. In addition, the structure of homoallyl sulfur-
success of the reaction and various aryl and alkyl-substituted containing pyrazolone derivative 3a was assigned unambigu-
alkylidene pyrazolinones
1
was adaptable to the ously by using single crystal X-ray analysis.16
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Subsequently, we went on to evaluate the effect of different
substituents on pyrazolinone ring (Scheme 3). a-Alkylidene
pyrazolinones 1 with the para-substituted phenyl-ring of R1
worked well to deliver the corresponding products 3aa, 3ab, 3ac
and 3ad with moderate yields of 63, 60, 73 and 66%, respec-
tively. Electron-withdrawing groups on the phenyl group gave
better yields than electron-donating groups (3ac, 3ad vs. 3aa,
3ab). ortho-Ethyl, uoro-substituted phenyl ring of R1 gave
relatively lower yields of 50 and 55% partially because of the
instability of 1. It is noteworthy that the substrate having
electron-withdrawing group C6F5- supplied the desired product
3ag with a moderate yield of 70%. a-Alkylidene pyrazolinones 1
with 4-uoro-, 4-methoxy and 4-bromo-substituted phenyl ring
of R2 could also be applied to the reaction and provide the
related homoallyl sulfur-containing pyrazolones 3ah, 3ai and
3aj with 51, 71 and 50% yields. a-Alkylidene pyrazolinones 1
including alkyl group of R2 showed excellent compatibility and
afforded 3ak with 83% yield. Moreover, trimethyl involved
alkylidene pyrazolinone displayed proof of tolerance and 81%
Scheme 4 Scope of propargyl sulfonium salts.a Unless otherwise
noted, the reactions were performed under air and a-alkylidene pyr-
azolinone 1a or 1d (0.2 mmol, 1.0 equiv.), sulfonium salts 2b, 2c or 2d
(0.24 mmol, 1.2 equiv.) and NaOAc$3H2O (0.1 mmol, 0.5 equiv.) in
CH3CN (2.0 mL) were mixed and stirred at 20 ꢀC until starting material yield was obtained (3al).
1a or 1d disappeared (monitored by TLC), then the reaction temper-
To further broaden the scope of the reaction, other repre-
ature was decreased to 0 ꢀC and KOH (2.0 equiv.) was added to keep
stirring at 0 ꢀC for related time. bIsolated yield.c Cs2CO3 (0.1 mmol, 0.5
equiv.) was utilized instead of NaOAc$3H2O under the standard
condition and the reaction was kept stirring at 0 ꢀC for 15 h.
sentative propargyl sulfonium salts were also investigated
(Scheme 4). Diethyl thioether derived propargyl sulfonium salt
2b was adaptable to give the predicted homoallyl sulfur-
containing pyrazolone 4 in 23% yield, together with addi-
tional isomerization product 5 in 47% yield. Trimethylsilyl-
containing propargyl sulfonium salt 2c can also be applied to
the reaction but the desilylation product 3a was obtained with
a yield of 79%. Methyl substituted propargyl sulfonium salt 2d
did not engage in the reaction under standard condition,
mainly because NaOAc$3H2O was not suitable to transform
propargyl sulfonium salt 2d into active allenic form and alky-
lidene pyrazolinone 1a was nearly fully recovered aer stirred at
20 ꢀC for 20 h. When NaOAc$3H2O was replaced by Cs2CO3, the
reaction could proceed to afford the desired product 6 with 62%
yield. Substrate 1d could also react with 2d smoothly to provide
7 with 68% yield under the same conditions.
Scheme 5 Gram-scale synthesis and further transformation of 3a.
To demonstrate the further synthetic utility of this protocol,
we performed the large-scale operation using a-alkylidene pyr-
azolinone 1a (1.01 g, 3 mmol) and propargyl sulfonium salt 2a
(1.2 equiv.) as the representative substrates under the optimized
conditions, providing the related product 3a (1.00 g) with 79%
yield (Scheme 5). The typical transformation was also con-
ducted by oxidation of 3a with m-chloro peroxybenzoic acid (2.0
equiv.), sulnyl product 8 and sulfonyl product 9 were obtained
in Scheme 5 with 33% and 39% yields, respectively.
According to the experimental observations and previous
reports,8,9,14 a possible mechanism is proposed to account for
the formation of homoallyl sulfur-containing pyrazolone
derivatives 3 (Scheme 6). Under the activation of inorganic base
NaOAc$3H2O, a-alkylidene pyrazolone 1 can form intermediate
I and propargyl sulfonium salt 2a can isomerize to allenic
sulfonium salts II. The N-nucleophilic attack of I to allenic
sulfonium salts II initiates the reaction and gives intermediate
III aer protonation. Subsequently, the deprotonation of
methyl-carbon by KOH provides the key sulfur ylide IV. Finally,
Scheme 6 Plausible reaction mechanism.
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the [2,3]-sigmatropic rearrangement of key species IV affords isopropoxide (4.3 mL, 15 mmol). The mixture was stirred at
the desired product 3.
room temperature for 24 h. The resulting reaction mixture was
diluted with EtOAc (100 mL) and washed with 1 N aqueous HCl,
saturated aqueous solution of NaHCO3 and brine. The organic
layer was dried over Na2SO4, concentrated, and puried by
column chromatography to provide a-alkylidene pyrazolinone
derivatives 1. If the products are mixed with excess liquid ace-
tophenes, they can be further puried by washing with petro-
leum ether.
Conclusions
In summary, we have developed a sequentially combined inor-
ganic bases promoted N-addition/[2,3]-sigmatropic rearrange-
ment reaction between a-alkylidene pyrazolinones and
propargyl sulfonium salts for the rst time, delivering bioactive
homoallyl sulfur-containing pyrazolones in moderate to excel-
lent yields. In this reaction, a-alkylidene pyrazolinones function
as N-nucleophilic agents distinguished from reported C-
addition reactions. Meanwhile, propargyl sulfonium salts were
rst involved in [2,3]-sigmatropic rearrangement protocols
differentiated from the well-established annulation reactions.
Gram-scale synthesis and convenient transformations are fur-
nished. The proposed mechanism is also discussed. Excellent
regioselectivity, the broad scope of substrates, gram-scale
synthesis and convenient transformation embody the
synthetic superiority of this reaction process.
Propargyl Sulfonium Salts (2a, 2b, 2c, 2d and 2e) were
prepared through a known procedure.18
General procedure for the reaction of unsaturated pyrazolones
with propargyl sulde ylide
To a ame-dried sealable 3-dram vial equipped with a stir bar
was added unsaturated pyrazolinones 1 (0.2 mmol, 1.0 equiv.),
NaOAc$3H2O (0.1 mmol, 0.5 equiv.) and 2a (44 mg, 0.24 mmol,
1.2 equiv.) under air. Subsequently treated CH3CN (2 mL, c ¼ 0.1
M) was added to vial via syringe. The reaction mixture was
ꢀ
stirred for 10–40 min at 20 C until unsaturated pyrazolones 1
was fully consumed (monitored by TLC). Then the reaction was
stirred at 0 ꢀC for 6–10 h. The organic solvent was removed
under reduced pressure and puried through column chro-
matography (eluent: petroleum ether and EtOAc) to afford the
desired product 3.
Experimental
General information
All reactions were performed in oven-dried or ame-dried
round-bottom asks and vials. Stainless steel syringes and
cannula were used to transfer air- and moisture-sensitive
liquids. Flash chromatography was performed using silica gel
60 (230–400 mesh) from Aladdin. Commercial reagents were
purchased from Aladdin, J&K, Macklin and Meryer and used as
received. All solvents were used aer being freshly distilled
unless otherwise noted. Proton nuclear magnetic resonance (1H
1-(4-(Methylthio)but-1-en-2-yl)-2,5-diphenyl-4-(1-phenylvinyl)-1,2-
dihydro-3H-pyrazol-3-one (3a)
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3a was puried through
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
obtained as a white solid (75 mg, 85% yield). mp 174.7–175.6 ꢀC.
IR nmax (neat)/cmꢁ1: 3062, 2985, 1677, 1568, 1452, 1391, 1183,
1026, 955; 1H NMR (600 MHz, CDCl3): d 7.62 (dd, J ¼ 1.2, 7.8 Hz,
2H), 7.47 (t, J ¼ 7.8 Hz, 2H), 7.34–7.29 (m, 5H), 7.26 (d, J ¼
7.2 Hz, 1H), 7.23 (t, J ¼ 7.2 Hz, 2H), 7.17 (t, J ¼ 7.8 Hz, 2H), 7.13
(t, J ¼ 7.2 Hz, 1H), 5.69 (d, J ¼ 1.2 Hz, 1H), 5.65 (d, J ¼ 1.2 Hz,
1H), 5.45 (s, 1H), 5.06 (s, 1H), 2.24 (t, J ¼ 7.8 Hz, 2H), 2.05 (t, J ¼
7.8 Hz, 2H), 1.94 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3):
d 164.6, 155.6, 145.1, 140.2, 138.3, 135.9, 130.0, 129.6, 129.2,
128.7, 127.9, 127.9, 127.2, 126.9, 126.4, 124.2, 118.9, 117.9,
NMR) spectra and carbon nuclear magnetic resonance (13
NMR) spectra were recorded on Bruker UltraShield-600 (600
MHz). The mass spectroscopic data were obtained using
C
a
Micromass Platform II single quadrupole instrument.
Infrared (IR) spectra were obtained using a PerkinElmer Spec-
trum 100 FT-IR spectrometer.
General procedure for the synthesis of a-alkylidene
pyrazolinones (1)
114.3, 31.3, 31.1, 15.3. HRMS (ESI-TOF, m/z): calcd for C28H26
-
a-Alkylidene pyrazolinones 1 were prepared through a known
procedure:12b,13b,14,17 aryl formyl acetate (5.5 mmol, 1.1 equiv.)
was slowly added to the mixture of the corresponding hydrazine
(5 mmol, 1.0 equiv.) in glacial acetic acid (2 mL). The mixture
was stirred at room temperature for 24 h. NEt3 (5 mmol, 1.0
N2NaOS+, [M + Na]+, 461.1658, found 461.1662.
1-(4-(Methylthio)but-1-en-2-yl)-2,5-diphenyl-4-(1-(p-tolyl)vinyl)-1,2-
dihydro-3H-pyrazol-3-one (3b)
equiv.) was added to neutralize the hydrochloride while phe- The reaction was carried out on a 0.2 mmol scale following the
nylhydrazine hydrochloride was used. Aer the reaction was General procedure. The product 3b was puried through
completed, ethyl (50 mL) was added. The precipitate was ltered column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
and washed with 5 mL of ether (three times). The corresponding obtained as a foam solid (59 mg, 65% yield). IR nmax (neat)/
pyrozolone products were obtained as solid and used in the cmꢁ1: 3102, 2899, 1698, 1571, 1433, 1367, 1256, 1142, 1030, 979;
following step.
1H NMR (600 MHz, CDCl3): d 7.62 (dd, J ¼ 0.6, 8.4 Hz, 2H), 7.46
Under nitrogen atmosphere,
a
mixture of pyrazolone (t, J ¼ 7.8 Hz, 2H), 7.36 (d, J ¼ 8.4 Hz, 2H), 7.31–7.30 (m, 2H),
(5 mmol, 1.0 equiv.), acetophenone (6 mmol, 1.2 equiv.) and 7.28–7.23 (m, 4H), 7.00 (d, J ¼ 7.8 Hz, 2H), 5.64 (d, J ¼ 1.2 Hz,
pyridine (0.8 mL, 10 mmol) in THF (10 mL) was stirred for 1H), 5.49 (d, J ¼ 1.2 Hz, 1H), 5.44 (s, 1H), 5.06 (s, 1H), 2.28 (s,
10 min followed by slow addition (30 min) of Titanium 3H), 2.26 (t, J ¼ 7.8 Hz, 2H), 2.06 (t, J ¼ 7.8 Hz, 2H), 1.95 (s, 3H);
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13C{1H} NMR (150 MHz, CDCl3): d 164.7, 155.6, 145.3, 138.2,
137.4, 137.0, 136.1, 130.1, 129.6, 129.4, 128.7, 127.9, 126.8,
126.4, 124.1, 118.0, 117.8, 114.8, 31.4, 31.1, 21.0, 15.4. HRMS
(ESI-TOF, m/z): calcd for C29H28N2ONaS+, [M + Na]+, 475.1815,
found 475.1812.
4-(1-(4-Iodophenyl)vinyl)-1-(4-(methylthio)but-1-en-2-yl)-2,5-
diphenyl-1,2-dihydro-3H-pyrazol-3-one (3f)
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3f was puried through
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
obtained as a foam solid (71 mg, 63% yield). IR nmax (neat)/
4-(1-(4-Methoxyphenyl)vinyl)-1-(4-(methylthio)but-1-en-2-yl)-2,5-
diphenyl-1,2-dihydro-3H-pyrazol-3-one (3c)
1
cmꢁ1: 3082, 2986, 1677, 1598, 1465, 1343, 1188, 1067, 962; H
NMR (600 MHz, CDCl3): d 7.60 (dd, J ¼ 1.2, 7.8 Hz, 2H), 7.48–
7.45 (m, 4H), 7.32–7.28 (m, 4H), 7.25 (d, J ¼ 7.2 Hz, 2H), 7.03 (d, J
¼ 8.4 Hz, 2H), 5.67 (d, J ¼ 1.2 Hz, 1H), 5.64 (d, J ¼ 1.2 Hz, 1H),
5.42 (s, 1H), 5.06 (s, 1H), 2.23 (t, J ¼ 7.8 Hz, 2H), 2.04 (t, J ¼
7.8 Hz, 2H), 1.93 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3):
d 164.3, 155.5, 144.9, 139.9, 137.5, 137.0, 135.8, 130.0, 129.7,
129.1, 128.8, 128.7, 128.0, 126.5, 124.2, 119.3, 117.9, 113.4, 92.7,
31.2, 15.3. HRMS (ESI-TOF, m/z): calcd for C28H25IN2ONaS+, [M
+ Na]+, 587.0624, found 587.0620.
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3c was puried through
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
obtained as a foam solid (76 mg, 81% yield). IR nmax (neat)/
cmꢁ1: 3087, 2977, 1664, 1582, 1456, 1361, 1129, 1057, 933, 854;
1H NMR (600 MHz, CDCl3): d 7.62 (d, J ¼ 7.2 Hz, 2H), 7.46 (t, J ¼
7.8 Hz, 2H), 7.36 (d, J ¼ 7.2 Hz, 2H), 7.30–7.24 (m, 6H), 6.72 (d, J
¼ 9.0 Hz, 2H), 5.60 (d, J ¼ 1.2 Hz, 1H), 5.48 (d, J ¼ 1.2 Hz, 1H),
5.45 (s, 1H), 5.06 (s, 1H), 3.75 (s, 3H), 2.24 (t, J ¼ 7.8 Hz, 2H), 2.05
(t, J ¼ 7.8 Hz, 2H), 1.94 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3):
d 164.5, 159.1, 155.5, 145.1, 137.6, 135.9, 132.8, 129.9, 129.5,
129.2, 128.6, 127.9, 127.8, 126.3, 124.0, 117.8, 117.1, 114.6,
113.5, 55.2, 31.3, 31.0, 15.3. HRMS (ESI-TOF, m/z): calcd for
1-(4-(Methylthio)but-1-en-2-yl)-4-(1-(4-nitrophenyl)vinyl)-2,5-
diphenyl-1,2-dihydro-3H-pyrazol-3-one (3g)
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3g was puried through column
chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and obtained as
a foam solid (57 mg, 59% yield). IR nmax (neat)/cmꢁ1: 3076, 2977,
1668, 1599, 1472, 1338, 1169, 1027, 912, 835; 1H NMR (600 MHz,
CDCl3): d 7.98 (d, J ¼ 9.0 Hz, 2H), 7.60 (dd, J ¼ 1.2, 8.4 Hz, 2H),
7.49 (t, J ¼ 7.8 Hz, 2H), 7.39 (d, J ¼ 8.4 Hz, 2H), 7.33 (t, J ¼ 7.8 Hz,
1H), 7.27–7.25 (m, 3H), 7.22 (t, J ¼ 7.2 Hz, 2H), 5.96 (d, J ¼ 0.6 Hz,
1H), 5.77 (d, J ¼ 0.6 Hz, 1H), 5.45 (s, 1H), 5.08 (s, 1H), 2.23 (t, J ¼
7.8 Hz, 2H), 2.04 (t, J ¼ 7.8 Hz, 2H), 1.94 (s, 3H); 13C{1H} NMR
(150 MHz, CDCl3): d 164.1, 155.4, 147.1, 144.7, 137.0, 135.7, 130.1,
130.0, 128.9, 128.2, 128.0, 127.9, 126.8, 124.4, 123.2, 121.9, 118.2,
112.5, 31.5, 31.3, 15.4. HRMS (ESI-TOF, m/z): calcd for C28H25-
N3O3NaS+, [M + Na]+, 506.1509, found 506.1509.
C
29H29N2O2S+, [M + H]+, 469.1944, found 469.1943.
4-(1-(4-Chlorophenyl)vinyl)-1-(4-(methylthio)but-1-en-2-yl)-
2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3d)
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3d was puried through
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
obtained as a foam solid (71 mg, 75% yield). IR nmax (neat)/
1
cmꢁ1: 3073, 2956, 1680, 1479, 1364, 1182, 1036, 937; H NMR
(600 MHz, CDCl3): d 7.60 (dd, J ¼ 1.2, 8.4 Hz, 2H), 7.47 (t, J ¼
8.4 Hz, 2H), 7.30 (d, J ¼ 8.4 Hz, 4H), 7.25 (d, J ¼ 7.8 Hz, 2H),
7.23–7.21 (m, 2H), 7.11 (d, J ¼ 8.4 Hz, 2H), 5.69 (d, J ¼ 1.2 Hz,
1H), 5.65 (d, J ¼ 1.2 Hz, 1H), 5.44 (s, 1H), 5.06 (s, 1H), 2.23 (t, J ¼
7.8 Hz, 2H), 2.04 (t, J ¼ 7.8 Hz, 2H), 1.93 (s, 3H); 13C{1H} NMR
(150 MHz, CDCl3): d 164.3, 155.5, 144.9, 138.8, 137.3, 135.7,
133.1, 130.0, 129.7, 129.1, 128.8, 128.2, 128.0, 128.0, 126.5,
124.2, 119.3, 118.0, 113.6, 31.2, 15.3. HRMS (ESI-TOF, m/z):
calcd for C28H26ClN2OS+, [M + H]+, 473.1449, found 473.1451.
4-(1-(1-(4-(Methylthio)but-1-en-2-yl)-3-oxo-2,5-diphenyl-2,3-
dihydro-1H-pyrazol-4-yl)vinyl) benzonitrile (3h)
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3h was puried through
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
obtained as a foam solid (84 mg, 91% yield). IR nmax (neat)/
cmꢁ1: 3065, 2963, 2023, 1672, 1564, 1491, 1336, 1287, 1142,
1053, 965; 1H NMR (600 MHz, CDCl3): d 7.58 (d, J ¼ 7.2 Hz, 2H),
7.48 (t, J ¼ 7.8, 2H), 7.39 (d, J ¼ 7.2, 2H), 7.30–7.34 (m, 3H), 7.28
(d, J ¼ 3.6 Hz, 1H), 7.27–7.25 (m, 2H), 7.22 (d, J ¼ 7.2 Hz, 2H),
5.90 (s, 1H), 5.72 (s, 1H), 5.44 (s, 1H), 5.07 (s, 1H), 2.22 (t, J ¼
7.8 Hz, 2H), 2.03 (t, J ¼ 7.8 Hz, 2H), 1.92 (s, 3H); 13C{1H} NMR
(150 MHz, CDCl3): d 164.1, 155.4, 145.1, 144.7, 137.2, 135.7,
131.7, 130.0, 128.9, 128.1, 127.7, 126.8, 124.3, 121.4, 118.7,
118.2, 112.5, 110.9, 31.4, 31.2, 15.4. HRMS (ESI-TOF, m/z): calcd
for C29H25IN3ONaS+, [M + Na]+, 486.1611, found 486.1610.
4-(1-(4-Bromophenyl)vinyl)-1-(4-(methylthio)but-1-en-2-yl)-2,5-
diphenyl-1,2-dihydro-3H-pyrazol-3-one (3e)
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3e was puried through
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
obtained as a foam solid (87 mg, 84% yield). IR nmax (neat)/
cmꢁ1: 3102, 2941, 1668, 1603, 1490, 1377, 1268, 1146, 1021, 919,
832; 1H NMR (600 MHz, CDCl3): d 7.60 (d, J ¼ 7.8 Hz, 2H), 7.46
(t, J ¼ 7.8 Hz, 2H), 7.31–7.26 (m, 5H), 7.25–7.22 (m, 3H), 7.15 (d,
J ¼ 8.4 Hz, 2H), 5.69 (d, J ¼ 0.6 Hz, 1H), 5.64 (d, J ¼ 0.6 Hz, 1H),
5.42 (s, 1H), 5.05 (s, 1H), 2.23 (t, J ¼ 7.8 Hz, 2H), 2.04 (t, J ¼
7.8 Hz, 2H), 1.93 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3):
d 164.3, 155.4, 144.8, 139.3, 137.3, 135.7, 131.0, 129.9, 129.7,
129.0, 128.7, 128.5, 128.0, 126.5, 124.1, 121.2, 119.2, 118.0,
1-(4-(Methylthio)but-1-en-2-yl)-2,5-diphenyl-4-(1-(m-tolyl)vinyl)-
1,2-dihydro-3H-pyrazol-3-one (3i)
113.4, 31.2, 15.3. HRMS (ESI-TOF, m/z): calcd for C28H26BrN2- The reaction was carried out on a 0.2 mmol scale following the
OS+, [M + H]+, 517.0944, found 517.0945.
General procedure. The product 3i was puried through column
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chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and obtained as a foam solid (80 mg, 88% yield). IR nmax (neat)/cmꢁ1: 3106, 3023,
a foam solid (79 mg, 87% yield). IR nmax (neat)/cmꢁ1: 3106, 2932, 2984, 1688, 1492, 1356, 1149, 1028, 972, 855; 1H NMR (600 MHz,
1688, 1492, 1356, 1149, 1028, 972, 855; 1H NMR (600 MHz, CDCl3): d 7.59 (d, J ¼ 7.2 Hz, 2H), 7.47 (t, J ¼ 7.2 Hz, 2H), 7.30 (t, J
CDCl3): d 7.64 (dd, J ¼ 1.2, 8.4 Hz, 2H), 7.47 (t, J ¼ 7.8 Hz, 2H), ¼ 7.2 Hz, 1H), 7.19–7.16 (m, 1H), 7.12–7.09 (m, 4H), 6.95 (dd, J ¼
7.34 (d, J ¼ 7.2 Hz, 2H), 7.29 (t, J ¼ 7.8 Hz, 1H), 7.26 (d, J ¼ 1.2, 7.2 Hz, 1H), 6.90 (dt, J ¼ 1.2, 7.2 Hz, 1H), 6.86 (t, J ¼ 7.2 Hz,
7.2 Hz, 1H), 7.23 (t, J ¼ 7.2 Hz, 2H), 7.13 (d, J ¼ 7.8 Hz, 1H), 7.09 1H), 6.81 (d, J ¼ 7.8 Hz, 1H), 6.25 (d, J ¼ 1.8 Hz, 1H), 5.37 (d, J ¼
(d, J ¼ 6.0 Hz, 1H), 7.06 (d, J ¼ 7.2 Hz, 1H), 6.94 (d, J ¼ 7.2 Hz, 1.8 Hz, 1H), 5.22 (s, 1H), 4.93 (s, 1H), 2.20 (t, J ¼ 7.8 Hz, 2H), 2.10
1H), 5.67 (d, J ¼ 1.2 Hz, 1H), 5.64 (d, J ¼ 1.2 Hz, 1H), 5.44 (s, 1H), (s, 3H), 2.00 (t, J ¼ 7.8 Hz, 2H), 1.93 (s, 3H); 13C{1H} NMR (150
5.05 (s, 1H), 2.26 (t, J ¼ 7.8 Hz, 2H), 2.25 (s, 3H), 2.06 (t, J ¼ MHz, CDCl3): d 164.2, 154.4, 144.5, 141.1, 138.3, 135.9, 135.7,
7.8 Hz, 2H), 1.95 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): 134.8, 129.7, 129.6, 129.5, 129.1, 128.7, 127.3, 126.7, 126.4,
d 164.6, 155.5, 145.1, 140.1, 138.4, 137.2, 136.0, 130.0, 129.5, 124.9, 124.0, 120.1, 117.0, 112.9, 31.5, 31.0, 19.9, 15.2. HRMS
129.3, 128.7, 128.0, 127.8, 127.8, 127.7, 126.3, 124.1, 118.5, (ESI-TOF, m/z): calcd for C29H28N2NaOS+, [M + Na]+, 475.1815,
117.8, 114.3, 31.3, 31.1, 21.2, 15.3. HRMS (ESI-TOF, m/z): calcd found 475.1813.
for C29H29N2OS+, [M + H]+, 453.1995, found 453.1993.
4-(1-(2-Methoxyphenyl)vinyl)-1-(4-(methylthio)but-1-en-2-yl)-
4-(1-(3-Methoxyphenyl)vinyl)-1-(4-(methylthio)but-1-en-2-yl)-2,5-
diphenyl-1,2-dihydro-3H-pyrazol-3-one (3j)
2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3m)
The reaction was carried out on a 0.2 mmol scale following the
The reaction was carried out on a 0.2 mmol scale following the General procedure. The product 3m was puried through
General procedure. The product 3j was puried through column column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and obtained as obtained as a foam solid (79 mg, 84% yield). IR nmax (neat)/
1
a foam solid (77 mg, 82% yield). IR nmax (neat)/cmꢁ1: 3088, 2898, cmꢁ1: 3078, 2983, 1660, 1576, 1469, 1337, 1147, 1053, 983; H
1667, 1584, 1492, 1336, 1177, 1062, 946; 1H NMR (600 MHz, NMR (600 MHz, CDCl3): d 7.59 (d, J ¼ 7.2 Hz, 2H), 7.45 (t, J ¼
CDCl3): d 7.62 (d, J ¼ 7.2 Hz, 2H), 7.46 (t, J ¼ 7.8 Hz, 2H), 7.34 (d, 7.8 Hz, 2H), 7.27–7.25 (m, 3H), 7.21 (t, J ¼ 7.2 Hz, 1H), 7.15 (t, J ¼
J ¼ 7.2 Hz, 2H), 7.30–7.26 (m, 2H), 7.23 (t, J ¼ 7.2 Hz, 2H), 7.08 (t, 7.2 Hz, 2H), 7.13 (d, J ¼ 7.2 Hz, 1H), 7.04 (dt, J ¼ 1.8, 8.4 Hz, 1H),
J ¼ 7.8 Hz, 1H), 6.92 (d, J ¼ 7.8 Hz, 1H), 6.83 (s, 1H), 6.68 (dd, J ¼ 6.75 (dt, J ¼ 0.6, 7.2 Hz, 1H), 6.53 (d, J ¼ 8.4 Hz, 1H), 6.03 (d, J ¼
1.8, 7.8 Hz, 1H), 5.68 (d, J ¼ 1.2 Hz, 1H), 5.67 (s, 1H), 5.43 (s, 1H), 1.8 Hz, 1H), 5.44 (d, J ¼ 1.8 Hz, 1H), 5.30 (s, 1H), 4.96 (s, 1H),
5.05 (s, 1H), 3.74 (s, 3H), 2.24 (t, J ¼ 7.8 Hz, 2H), 2.05 (t, J ¼ 3.68 (s, 3H), 2.22 (t, J ¼ 7.8 Hz, 2H), 2.02 (t, J ¼ 7.8 Hz, 2H), 1.93
7.8 Hz, 2H), 1.94 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): d 164.6, 156.4, 154.4,
d 164.5, 159.4, 155.5, 145.1, 141.7, 138.2, 135.9, 130.0, 129.6, 145.1, 136.2, 130.6, 130.1, 129.4, 129.1, 128.6, 128.4, 127.3,
129.2, 128.9, 128.7, 127.8, 126.4, 124.1, 119.7, 118.9, 117.9, 126.1, 123.9, 120.2, 117.1, 113.8, 110.5, 55.3, 31.2, 15.2. HRMS
114.2, 113.0, 112.9, 55.1, 31.3, 31.1, 15.3. HRMS (ESI-TOF, m/z): (ESI-TOF, m/z): calcd for C29H28N2NaO2S+, [M + Na]+, 491.1764,
calcd for C29H28N2NaO2S+, [M + Na]+, 491.1764, found 491.1764. found 491.1766.
4-(1-(3-Chlorophenyl)vinyl)-1-(4-(methylthio)but-1-en-2-yl)-2,5-
diphenyl-1,2-dihydro-3H-pyrazol-3-one (3k)
4-(1-(2-Chlorophenyl)vinyl)-1-(4-(methylthio)but-1-en-2-yl)-2,5-
diphenyl-1,2-dihydro-3H-pyrazol-3-one (3n)
The reaction was carried out on a 0.2 mmol scale following the The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3k was puried through General procedure. The product 3n was puried through
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
obtained as a foam solid (80 mg, 85% yield). IR nmax (neat)/ obtained as a foam solid (84 mg, 89% yield). IR nmax (neat)/
1
1
cmꢁ1: 3074, 2973, 1679, 1563, 1455, 1383, 1257, 1061, 977; H cmꢁ1: 3056, 2933, 1679, 1586, 1453, 1332, 1175, 1026, 944; H
NMR (600 MHz, CDCl3): d 7.61 (d, J ¼ 7.2 Hz, 2H), 7.47 (t, J ¼ NMR (600 MHz, CDCl3): d 7.58 (d, J ¼ 7.2 Hz, 2H), 7.45 (t, J ¼
7.8 Hz, 2H), 7.31–7.30 (m, 3H), 7.29–7.21 (m, 4H), 7.15 (dt, J ¼ 7.2 Hz, 2H), 7.29 (t, J ¼ 7.2 Hz, 1H), 7.23–7.18 (m, 3H), 7.17 (d, J
1.8, 4.8 Hz, 1H), 7.05 (d, J ¼ 4.8 Hz, 2H), 5.81 (d, J ¼ 1.2 Hz, 1H), ¼ 6.6 Hz, 2H), 7.07 (dd, J ¼ 1.8, 6.6 Hz, 1H), 7.03 (dd, J ¼ 1.8,
5.66 (d, J ¼ 1.2 Hz, 1H), 5.42 (s, 1H), 5.05 (s, 1H), 2.23 (t, J ¼ 6.6 Hz, 1H), 6.96–6.92 (m, 2H), 6.23 (d, J ¼ 1.2 Hz, 1H), 5.43 (d, J
7.8 Hz, 2H), 2.04 (t, J ¼ 7.8 Hz, 2H), 1.94 (s, 3H); 13C{1H} NMR ¼ 1.2 Hz, 1H), 5.24 (s, 1H), 4.94 (s, 1H), 2.22 (t, J ¼ 7.8 Hz, 2H),
(150 MHz, CDCl3): d 164.3, 155.4, 144.8, 142.2, 137.2, 135.8, 2.02 (t, J ¼ 7.8 Hz, 2H), 1.93 (s, 3H); 13C{1H} NMR (150 MHz,
133.8, 130.0, 129.7, 129.1, 128.8, 127.9, 127.3, 127.1, 126.5, CDCl3): d 164.2, 154.2, 144.5, 139.9, 136.5, 135.9, 132.3, 131.3,
125.2, 124.2, 119.8, 118.0, 113.1, 31.3, 31.2, 15.3. HRMS (ESI- 129.9, 129.2, 129.1, 128.7, 128.0, 127.5, 126.4, 126.0, 124.1,
TOF, m/z): calcd for C28H25ClN2NaOS+, [M + Na]+, 495.1268, 121.1, 117.1, 112.0, 31.7, 31.0, 15.2. HRMS (ESI-TOF, m/z): calcd
found 495.1265.
for C28H25ClN2NaOS+, [M + Na]+, 495.1268, found 495.1270.
1-(4-(Methylthio)but-1-en-2-yl)-2,5-diphenyl-4-(1-(o-tolyl)
vinyl)-1,2-dihydro-3H-pyrazol-3-one (3l)
1-(4-(Methylthio)but-1-en-2-yl)-4-(1-(naphthalen-2-yl)vinyl)-
2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3o)
The reaction was carried out on a 0.2 mmol scale following the The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3l was puried through column General procedure. The product 3o was puried through
chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and obtained as column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
34918 | RSC Adv., 2019, 9, 34912–34925
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obtained as a foam solid (65 mg, 66% yield). IR nmax (neat)/ column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
1
cmꢁ1: 3113, 2965, 1680, 1566, 1473, 1357, 1121, 1073, 961; H obtained as a foam solid (51 mg, 57% yield). IR nmax (neat)/
NMR (600 MHz, CDCl3): d 7.87 (dd, J ¼ 2.4, 7.2 Hz, 1H), 7.62 (d, J cmꢁ1: 3032, 2987, 1681, 1527, 1397, 1262, 1098, 1002, 935, 882;
¼ 4.8 Hz, 1H), 7.61 (t, J ¼ 7.2 Hz, 2H), 7.49 (t, J ¼ 7.2 Hz, 2H), 1H NMR (600 MHz, CDCl3): d 7.63 (d, J ¼ 7.8 Hz, 2H), 7.48–7.45
7.44 (d, J ¼ 7.8 Hz, 1H), 7.38–7.36 (m, 2H), 7.32 (t, J ¼ 7.2 Hz, (m, 4H), 7.37–7.29 (m, 4H), 7.09 (d, J ¼ 5.4 Hz, 1H), 6.95 (d, J ¼
1H), 7.13–7.08 (m, 2H), 6.95 (t, J ¼ 7.2 Hz, 1H), 6.79 (t, J ¼ 7.2 Hz, 3.6 Hz, 1H), 6.84 (dd, J ¼ 3.6, 5.4 Hz, 1H), 5.73 (s, 1H), 5.48 (s,
2H), 6.68 (d, J ¼ 7.8 Hz, 2H), 6.61 (d, J ¼ 2.4 Hz, 1H), 5.58 (d, J ¼ 1H), 5.34 (s, 1H), 5.08 (s, 1H), 2.26 (t, J ¼ 7.8 Hz, 2H), 2.06 (t, J ¼
2.4 Hz, 1H), 5.06 (s, 1H), 4.83 (s, 1H), 2.16 (t, J ¼ 7.8 Hz, 2H), 1.98 7.8 Hz, 2H), 1.94 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3):
(t, J ¼ 7.8 Hz, 2H), 1.91 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): d 164.1, 155.7, 145.0, 143.9, 135.8, 131.8, 129.8, 129.6, 129.0,
d 164.3, 154.8, 144.3, 139.5, 137.4, 136.0, 133.4, 131.4, 129.5, 128.7, 128.0, 127.0, 126.4, 125.1, 124.9, 124.4, 124.3, 124.2,
128.8, 128.7, 127.9, 127.3, 127.0, 126.8, 126.5, 126.0, 125.5, 118.1, 117.5, 114.2, 31.2, 31.0, 15.3. HRMS (ESI-TOF, m/z): calcd
125.2, 124.8, 124.1, 120.8, 116.7, 112.9, 32.0, 31.1, 15.3. HRMS for C26H25N2OS+, [M + H]+, 445.1403, found 445.1405.
(ESI-TOF, m/z): calcd for C32H28ClN2NaOS+, [M + Na]+, 511.1815,
found 511.1818.
4-(1-(1-Methyl-1H-pyrrol-2-yl)vinyl)-1-(4-(methylthio)but-1-en-
2-yl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3s)
1-(4-(Methylthio)but-1-en-2-yl)-4-(1-(naphthalen-2-yl)vinyl)-
2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3p)
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3s was puried through
The reaction was carried out on a 0.2 mmol scale following the column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
General procedure. The product 3p was puried through obtained as a foam solid (62 mg, 70% yield). IR nmax (neat)/
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and cmꢁ1: 3072, 2976, 1672, 1476, 1331, 1229, 1152, 1034, 913, 826;
obtained as a foam solid (74 mg, 76% yield). IR nmax (neat)/ 1H NMR (600 MHz, CDCl3): d 7.59 (d, J ¼ 7.8 Hz, 2H), 7.46 (t, J ¼
1
cmꢁ1: 3039, 2976, 1677, 1562, 1473, 1390, 1124, 973, 837; H 7.8 Hz, 2H), 7.31 (t, J ¼ 7.8 Hz, 4H), 7.28–7.25 (m, 2H), 6.29 (t, J ¼
NMR (600 MHz, CDCl3): d 7.76 (d, J ¼ 4.8 Hz, 2H), 7.74 (d, J ¼ 2.4 Hz, 1H), 5.92 (dd, J ¼ 1.8, 3.0 Hz, 1H), 5.85 (d, J ¼ 1.8 Hz,
7.2 Hz, 1H), 7.68–7.65 (m, 3H), 7.51–7.48 (m, 3H), 7.44–7.40 (m, 1H), 5.84 (s, 1H), 5.43 (d, J ¼ 1.8 Hz, 1H), 5.38 (s, 1H), 5.02 (s,
2H), 7.38–7.37 (m, 2H), 7.31 (t, J ¼ 7.2 Hz, 1H), 7.16–7.14 (m, 1H), 3.42 (s, 3H), 2.22 (t, J ¼ 7.8 Hz, 2H), 2.01 (t, J ¼ 7.8 Hz, 2H),
3H), 5.84 (s, 1H), 5.74 (s, 1H), 5.47 (s, 1H), 5.07 (s, 1H), 2.29 (t, J 1.93 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): d 164.3, 155.0,
¼ 7.8 Hz, 2H), 2.11 (t, J ¼ 7.8 Hz, 2H), 1.97 (s, 3H); 13C{1H} NMR 144.9, 135.8, 133.2, 129.7, 129.5, 128.7, 127.6, 126.4, 124.1,
(150 MHz, CDCl3): d 164.6, 155.7, 145.1, 138.3, 137.7, 135.9, 122.8, 119.4, 117.7, 114.0, 109.8, 107.2, 34.5, 31.2, 15.3. HRMS
133.2, 132.8, 129.9, 129.5, 129.1, 128.7, 128.1, 127.8, 127.5, (ESI-TOF, m/z): calcd for C27H27N3NaOS+, [M + Na]+, 464.1767,
127.3, 126.4, 126.0, 125.7, 125.6, 125.1, 124.1, 119.2, 117.9, found 464.1772.
114.3, 31.3, 31.2, 15.3. HRMS (ESI-TOF, m/z): calcd for C32H28
-
ClN2NaOS+, [M + Na]+, 511.1815, found 511.1816.
1-(4-(Methylthio)but-1-en-2-yl)-2,5-diphenyl-4-(prop-1-en-2-yl)-
1,2-dihydro-3H-pyrazol-3-one (3t)
4-(1-(6-Methoxynaphthalen-2-yl)vinyl)-1-(4-(methylthio)but-
1-en-2-yl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (3q)
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3t was puried through
The reaction was carried out on a 0.2 mmol scale following the column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
General procedure. The product 3q was puried through obtained as a foam solid (54 mg, 72% yield). IR nmax (neat)/
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and cmꢁ1: 3051, 2982, 1672, 1568, 2448, 1379, 1253, 1062, 937, 784;
obtained as a foam solid (86 mg, 83% yield). IR nmax (neat)/ 1H NMR (600 MHz, CDCl3): d 7.55 (d, J ¼ 7.8 Hz, 2H), 7.47–7.43
1
cmꢁ1: 3027, 2917, 1673, 1510, 1445, 1307, 1011, 904, 816; H (m, 7H), 7.28 (t, J ¼ 7.2 Hz, 1H), 5.46 (s, 1H), 5.31 (s, 1H), 5.15 (s,
NMR (600 MHz, CDCl3): d 7.69–7.65 (m, 4H), 7.56 (d, J ¼ 9.0 Hz, 1H), 4.98 (s, 1H), 2.21 (t, J ¼ 7.8 Hz, 2H), 1.99 (t, J ¼ 7.8 Hz, 2H),
1H), 7.50–7.47 (m, 3H), 7.39–7.38 (m, 2H), 7.30 (t, J ¼ 7.2 Hz, 1.93 (s, 3H), 1.77 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3):
1H), 7.17–7.16 (m, 4H), 7.11 (dd, J ¼ 2.4, 9.0 Hz, 1H), 7.05 (d, J ¼ d 164.3, 153.7, 144.9, 135.9, 133.8, 130.2, 129.8, 128.7, 128.2,
2.4 Hz, 1H), 5.81 (d, J ¼ 0.6 Hz, 1H), 5.67 (s, 1H), 5.47 (s, 1H), 126.4, 124.1, 117.4, 117.2, 114.7, 31.3, 31.2, 22.6, 15.3. HRMS
5.07 (s, 1H), 3.89 (s, 3H), 2.28 (t, J ¼ 7.8 Hz, 2H), 2.10 (t, J ¼ (ESI-TOF, m/z): calcd for C23H25N2OS+, [M + H]+, 377.5255,
7.8 Hz, 2H), 1.96 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): found 377.5256.
d 164.5, 157.6, 155.6, 145.0, 138.2, 135.9, 135.4, 133.9, 129.8,
129.5, 129.1, 128.7, 127.7, 126.4, 126.3, 125.7, 125.4, 124.0, 1-(4-(Methylthio)but-1-en-2-yl)-2,5-diphenyl-4-(thiophen-2-yl)-
118.4, 118.4, 117.9, 114.5, 105.8, 55.1, 31.2, 31.1, 15.3. HRMS 1,2-dihydro-3H-pyrazol-3-one (3aa)
(ESI-TOF, m/z): calcd for C33H30N2NaO2S+, [M + Na]+, 541.1920,
found 541.1922.
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3aa was puried through
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
1-(4-(Methylthio)but-1-en-2-yl)-2,5-diphenyl-4-(thiophen-2-
obtained as a foam solid (57 mg, 63% yield). IR nmax (neat)/
yl)-1,2-dihydro-3H-pyrazol-3-one (3r)
cmꢁ1: 3022, 2918, 1672, 1580, 1397, 1301, 1189, 1011, 934, 781;
The reaction was carried out on a 0.2 mmol scale following the 1H NMR (600 MHz, CDCl3): d 7.49 (d, J ¼ 8.4 Hz, 2H), 7.34–7.30
General procedure. The product 3r was puried through (m, 4H), 7.28–7.24 (m, 3H), 7.21 (t, J ¼ 7.2 Hz, 2H), 7.16 (t, J ¼
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7.2 Hz, 2H), 7.11 (t, J ¼ 7.2 Hz, 1H), 5.68 (d, J ¼ 1.2 Hz, 1H), 5.67 (t, J ¼ 7.8 Hz, 2H), 1.95 (s, 3H). 13C{1H} NMR (150 MHz, CDCl3):
(d, J ¼ 1.2 Hz, 1H), 5.41 (s, 1H), 5.04 (s, 1H), 2.40 (s, 3H), 2.25 (t, J d 164.5, 156.1, 145.2, 140.1, 138.2, 135.1, 131.9, 130.0, 129.8,
¼ 7.8 Hz, 2H), 2.05 (t, J ¼ 7.8 Hz, 2H), 1.95 (s, 3H). 13C{1H} NMR 129.7, 129.0, 127.9, 127.3, 126.9, 125.3, 119.8, 119.0, 118.0,
(150 MHz, CDCl3): d 164.5, 155.1, 145.1, 140.3, 138.4, 136.3, 114.5, 31.4, 30.9, 15.4. HRMS (ESI-TOF, m/z): calcd for C28H25
133.4, 130.0, 129.5, 129.3, 127.8, 127.8, 127.1, 126.9, 124.3, BrN2NaOS+, [M + Na]+, 539.0763, found 539.0763.
118.7, 117.8, 114.1, 31.2, 20.9, 15.3. HRMS (ESI-TOF, m/z): calcd
-
for C29H28N2NaOS+, [M + Na]+, 475.1815, found 475.1817.
2-(2-Ethylphenyl)-1-(4-(methylthio)but-1-en-2-yl)-5-phenyl-
4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (3ae)
2-(4-Methoxyphenyl)-1-(4-(methylthio)but-1-en-2-yl)-5-phenyl-4-
(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (3ab)
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3ae was puried through
The reaction was carried out on a 0.2 mmol scale following the column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
General procedure. The product 3ab was puried through obtained as a foam solid (47 mg, 50% yield). IR nmax (neat)/
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and cmꢁ1: 3038, 2933, 1681, 157, 1392, 1267, 1083, 962, 828; 1H
obtained as a foam solid (56 mg, 60% yield). IR nmax (neat)/ NMR (600 MHz, CDCl3): d 7.42 (d, J ¼ 6.6 Hz, 1H), 7.39 (dt, J ¼
1
cmꢁ1: 3030, 2944, 1677, 1589, 1491, 1270, 1086, 933, 812; H 1.2, 7.2 Hz, 1H), 7.35 (d, J ¼ 7.2 Hz, 1H), 7.32–7.29 (m, 5H), 7.23
NMR (600 MHz, CDCl3): d 7.50 (d, J ¼ 9.0 Hz, 2H), 7.32–7.30 (m, (d, J ¼ 7.2 Hz, 1H), 7.19 (t, J ¼ 7.2 Hz, 2H), 7.13 (t, J ¼ 7.2 Hz,
4H), 7.25 (t, J ¼ 7.2 Hz, 1H), 7.20 (t, J ¼ 7.2 Hz, 2H), 7.15 (t, J ¼ 2H), 7.09 (t, J ¼ 7.2 Hz, 1H), 5.74 (d, J ¼ 1.2 Hz, 1H), 5.72 (d, J ¼
7.2 Hz, 2H), 7.11 (t, J ¼ 7.2 Hz, 1H), 6.99 (d, J ¼ 9.0 Hz, 2H), 5.67 1.2 Hz, 1H), 5.20 (s, 1H), 4.99 (s, 1H), 2.91–2.84 (m, 1H), 2.73–
(s, 1H), 5.66 (s, 1H), 5.39 (s, 1H), 5.05 (s, 1H), 3.84 (s, 3H), 2.25 (t, 2.67 (m, 1H), 2.27–2.24 (m, 2H), 2.11–2.07 (m, 2H), 1.94 (s, 3H),
J ¼ 7.8 Hz, 2H), 2.04 (t, J ¼ 7.8 Hz, 2H), 1.95 (s, 3H); 13C{1H} 1.34 (t, J ¼ 7.2 Hz, 3H). 13C{1H} NMR (150 MHz, CDCl3): d 165.6,
NMR (150 MHz, CDCl3): d 164.7, 158.5, 154.7, 145.1, 140.4, 154.1, 144.8, 142.8, 140.5, 138.5, 134.4, 129.8, 129.5, 129.4,
138.5, 130.0, 129.5, 129.4, 128.9, 127.9, 127.8, 127.2, 127.0, 129.0, 127.9, 127.8, 127.1, 127.0, 126.2, 118.8, 118.0, 113.0, 32.1,
126.3, 118.7, 118.0, 114.3, 114.0, 55.5, 31.3, 15.3. HRMS (ESI- 31.1, 23.9, 15.4, 14.0. HRMS (ESI-TOF, m/z): calcd for C30H30
TOF, m/z): calcd for C29H29N2OS+, [M + H]+, 469.1944, found N2NaOS+, [M + Na]+, 489.1971, found 489.1972.
469.1946.
-
2-(2-Fluorophenyl)-1-(4-(methylthio)but-1-en-2-yl)-5-phenyl-
2-(4-Fluorophenyl)-1-(4-(methylthio)but-1-en-2-yl)-5-phenyl-
4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (3ac)
4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (3af)
The reaction was carried out on a 0.2 mmol scale following the
The reaction was carried out on a 0.2 mmol scale following the General procedure. The product 3af was puried through
General procedure. The product 3ac was puried through column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and obtained as a foam solid (50 mg, 55% yield). IR nmax (neat)/
obtained as a foam solid (67 mg, 73% yield). IR nmax (neat)/ cmꢁ1: 3062, 2983, 1668, 1549, 1433, 1327, 1252, 1098, 972, 819;
1
cmꢁ1: 3037, 2975, 1658, 1589, 1452, 1358, 1284, 1031, 982; H 1H NMR (600 MHz, CDCl3): d 7.51 (t, J ¼ 6.0 Hz, 1H), 7.41–7.37
NMR (600 MHz, CDCl3): d 7.60–7.57 (m, 2H), 7.32 (dd, J ¼ 7.2, (m, 1H), 7.33–7.25 (m, 4H), 7.23 (d, J ¼ 7.8 Hz, 3H), 7.20 (t, J ¼
8.4 Hz, 2H), 7.29 (t, J ¼ 6.6 Hz, 2H), 7.26 (d, J ¼ 7.2 Hz, 1H), 7.22 7.2 Hz, 2H), 7.13 (t, J ¼ 7.2 Hz, 2H), 7.09 (t, J ¼ 7.2 Hz, 1H), 5.74
(t, J ¼ 7.2 Hz, 2H), 7.18–7.15 (m, 4H), 7.13 (t, J ¼ 7.2 Hz, 1H), 5.68 (d, J ¼ 1.2 Hz, 1H), 5.70 (d, J ¼ 1.2 Hz, 1H), 5.39 (s, 1H), 5.05 (s,
(d, J ¼ 1.2 Hz, 1H), 5.64 (d, J ¼ 1.2 Hz, 1H), 5.42 (s, 1H), 5.07 (s, 1H), 2.27 (t, J ¼ 7.8 Hz, 2H), 2.08 (t, J ¼ 7.8 Hz, 2H), 1.94 (s, 3H);
1H), 2.26 (t, J ¼ 7.8 Hz, 2H), 2.04 (t, J ¼ 7.8 Hz, 2H), 1.95 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3): d 165.2, 158.8, 157.2, 155.2,
13C{1H} NMR (150 MHz, CDCl3): d 164.8, 161.9, 160.3, 155.7, 144.8, 140.3, 138.3, 130.1, 130.0, 129.8, 129.6, 129.1, 127.9,
145.2, 140.2, 138.4, 132.1, 130.0, 129.7, 129.2, 128.0, 127.3, 127.8, 127.1, 127.0, 124.3, 118.8, 118.4, 116.8, 116.7, 113.1, 31.5,
126.9, 126.1, 126.1, 119.0, 118.0, 115.8, 115.6, 114.3, 31.4, 31.1, 31.2, 15.3. 19F NMR (600 MHz, CDCl3): d ꢁ118.90. HRMS (ESI-
15.4. 19F NMR (600 MHz, CDCl3): d ꢁ114.98. HRMS (ESI-TOF, m/ TOF, m/z): calcd for C28H25FN2NaOS+, [M + Na]+, 479.1564,
z): calcd for C28H26FN2OS+, [M + H]+, 457.1744, found 457.1746. found 479.1566.
2-(4-Bromophenyl)-5-(4-methoxyphenyl)-1-(4-(methylthio)but-
1-en-2-yl)-4-(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (3ad)
1-(4-(Methylthio)but-1-en-2-yl)-2-(peruorophenyl)-5-phenyl-4-
(1-phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (3ag)
The reaction was carried out on a 0.2 mmol scale following the The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3ad was puried through General procedure. The product 3ag was puried through
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
obtained as a foam solid (68 mg, 66% yield). IR nmax (neat)/ obtained as a foam solid (74 mg, 70% yield). IR nmax (neat)/
1
cmꢁ1: 3033, 2989, 1668, 1565, 1487, 1312, 1220, 1101, 979, 856; cmꢁ1: 3066, 2952, 1561, 1445, 1270, 1184, 1077, 977, 835; H
1H NMR (600 MHz, CDCl3): d 7.59 (d, J ¼ 7.8 Hz, 2H), 7.52 (d, J ¼ NMR (600 MHz, CDCl3): d 7.32 (d, J ¼ 6.6 Hz, 2H), 7.28–7.26 (m,
8.4 Hz, 2H), 7.33 (d, J ¼ 7.2 Hz, 2H), 7.30 (d, J ¼ 7.2 Hz, 2H), 7.26 3H), 7.20 (t, J ¼ 7.2 Hz, 2H), 7.14 (dd, J ¼ 6.0, 7.8 Hz, 2H), 7.10 (t,
(d, J ¼ 7.2 Hz, 1H), 7.23 (t, J ¼ 7.2 Hz, 2H), 7.17 (t, J ¼ 7.2 Hz, J ¼ 7.2 Hz, 1H), 5.75 (d, J ¼ 1.2 Hz, 1H), 5.71 (d, J ¼ 1.2 Hz, 1H),
2H), 7.13 (t, J ¼ 7.2 Hz, 1H), 5.68 (d, J ¼ 0.6 Hz, 1H), 5.62 (d, J ¼ 5.40 (s, 1H), 5.14 (s, 1H), 2.33 (t, J ¼ 7.8 Hz, 2H), 2.11 (t, J ¼
0.6 Hz, 1H), 5.44 (s, 1H), 5.08 (s, 1H), 2.26 (t, J ¼ 7.8 Hz, 2H), 2.04 7.8 Hz, 2H), 1.96 (s, 3H); 13C{1H} NMR (150 MHz, CDCl3):
34920 | RSC Adv., 2019, 9, 34912–34925
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d 165.9, 157.2, 145.9, 145.3, 144.2, 141.3, 139.9, 138.9, 137.8, 133.3, 132.0, 131.5, 131.2, 131.1, 129.5, 128.3, 128.1, 127.4,
137.2, 130.2, 130.0, 129.7, 129.6, 128.6, 128.1, 128.0, 127.4, 127.0, 124.4, 124.2, 124.1, 119.1, 118.8, 118.1, 114.8, 31.4, 31.2,
126.9, 119.3, 118.5, 113.1, 111.8, 31.1, 31.1, 15.3. 19F NMR (600 21.0, 15.4. HRMS (ESI-TOF, m/z): calcd for C29H28BrN2OS+, [M +
MHz, CDCl3): d ꢁ142.99, ꢁ143.02, ꢁ151.13, ꢁ151.17, ꢁ151.21, H]+, 531.1100, found 531.1103.
ꢁ161.11, ꢁ161.14, ꢁ161.14, ꢁ161.18. HRMS (ESI-TOF, m/z):
calcd for C28H21F5N2NaOS+, [M + Na]+, 551.1187, found
551.1188.
5-Methyl-1-(4-(methylthio)but-1-en-2-yl)-2-phenyl-4-(1-
phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (3ak)
5-(4-Fluorophenyl)-1-(4-(methylthio)but-1-en-2-yl)-2-phenyl-4-(1-
phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (3ah)
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3ak was puried through
The reaction was carried out on a 0.2 mmol scale following the
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
General procedure. The product 3ah was puried through
obtained as a foam solid (62 mg, 83% yield). IR nmax (neat)/
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
cmꢁ1: 3072, 2916, 1667, 1539, 1420, 1331, 1298, 1032, 919, 827;
obtained as a foam solid (47 mg, 51% yield). IR nmax (neat)/
1H NMR (600 MHz, CDCl3): d 7.49 (d, J ¼ 7.2 Hz, 2H), 7.49–7.40
1
cmꢁ1: 3036, 2942, 1670, 1589, 1433, 1362, 1098, 937, 828; H
(m, 2H), 7.34 (t, J ¼ 7.2 Hz, 2H), 7.29 (t, J ¼ 7.2 Hz, 1H), 7.25 (t, J
NMR (600 MHz, CDCl3): d 7.61 (d, J ¼ 7.8 Hz, 2H), 7.47 (t, J ¼
¼ 7.2 Hz, 1H), 5.73 (d, J ¼ 1.2 Hz, 1H), 5.66 (d, J ¼ 1.2 Hz, 1H),
7.8 Hz, 2H), 7.32–7.30 (m, 3H), 7.27 (dd, J ¼ 1.2, 7.8 Hz, 2H),
5.38 (s, 1H), 5.27 (s, 1H), 2.36 (t, J ¼ 7.2 Hz, 2H), 2.23 (t, J ¼
7.17–7.13 (m, 3H), 6.90 (t, J ¼ 9.0 Hz, 2H), 5.72 (d, J ¼ 1.2 Hz,
1H), 5.70 (d, J ¼ 1.2 Hz, 1H), 5.44 (s, 1H), 5.08 (s, 1H), 2.24 (t, J ¼
7.8 Hz, 2H), 2.03 (t, J ¼ 7.8 Hz, 2H), 1.95 (s, 3H); 13C{1H} NMR
(150 MHz, CDCl3): d 164.5, 164.2, 162.5, 154.3, 145.2, 140.2,
138.2, 135.9, 132.0, 132.0, 128.8, 128.0, 127.4, 127.0, 126.5,
125.3, 124.2, 119.1, 118.2, 115.2, 115.1, 114.5, 31.3, 31.0, 15.4.
19F NMR (600 MHz, CDCl3): d ꢁ110.07. HRMS (ESI-TOF, m/z):
calcd for C28H26FN2OS+, [M + H]+, 457.1744, found 457.1744.
7.2 Hz, 2H), 2.03 (s, 3H), 1.98 (s, 3H); 13C{1H} NMR (150 MHz,
CDCl3): d 164.8, 152.1, 143.7, 141.0, 138.6, 136.4, 128.7, 128.3,
127.5, 126.9, 126.0, 123.2, 117.9, 115.4, 110.8, 32.6, 30.9, 15.4,
13.0. HRMS (ESI-TOF, m/z): calcd for C23H25N2OS+, [M + H]+,
377.1682, found 377.1686.
5-Methyl-1-(4-(methylthio)but-1-en-2-yl)-2-phenyl-4-(prop-
1-en-2-yl)-1,2-dihydro-3H-pyrazol-3-one (3al)
5-(4-Methoxyphenyl)-1-(4-(methylthio)but-1-en-2-yl)-4-(1-
phenylvinyl)-2-(p-tolyl)-1,2-dihydro-3H-pyrazol-3-one (3ai)
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3al was puried through
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
obtained as a foam solid (51 mg, 81% yield). IR nmax (neat)/
cmꢁ1: 3046, 2982, 1670, 1533, 1478, 1324, 1278, 1109, 1082, 952;
1H NMR (600 MHz, CDCl3): d 7.43–7.39 (m, 4H), 7.25–7.22 (m,
1H), 5.38 (s, 1H), 5.27 (s, 1H), 5.20 (d, J ¼ 1.2 Hz, 1H), 5.09 (d, J ¼
1.2 Hz, 1H), 2.32 (s, 3H), 2.31 (t, J ¼ 7.8 Hz, 2H), 2.18 (t, J ¼
7.8 Hz, 2H), 2.14 (s, 3H), 2.00 (s, 3H); 13C{1H} NMR (150 MHz,
CDCl3): d 164.7, 150.4, 144.0, 136.4, 135.9, 128.7, 126.0, 123.3,
115.8, 115.3, 112.5, 32.5, 31.0, 22.3, 15.4, 12.8. HRMS (ESI-TOF,
m/z): calcd for C18H22N2NaOS+, [M + Na]+, 337.1345, found
337.1345.
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 3ai was puried through
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and
obtained as a foam solid (69 mg, 71% yield). IR nmax (neat)/
cmꢁ1: 3052, 2989, 1671, 1489, 1345, 1287, 1176, 1044, 929, 817;
1H NMR (600 MHz, CDCl3): d 7.48 (d, J ¼ 8.4 Hz, 2H), 7.33 (d, J ¼
7.2 Hz, 2H), 7.27 (t, J ¼ 8.4 Hz, 4H), 7.17 (t, J ¼ 7.2 Hz, 2H), 7.13
(t, J ¼ 7.2 Hz, 1H), 6.73 (d, J ¼ 8.4 Hz, 2H), 5.70 (d, J ¼ 1.2 Hz,
1H), 5.64 (s, 1H), 5.43 (s, 1H), 5.06 (s, 1H), 3.75 (s, 3H), 2.39 (s,
3H), 2.25 (t, J ¼ 7.8 Hz, 2H), 2.04 (t, J ¼ 7.8 Hz, 2H), 1.95 (s, 3H);
13C{1H} NMR (150 MHz, CDCl3): d 164.8, 160.6, 155.1, 145.4,
140.2, 138.5, 136.2, 133.5, 131.4, 129.3, 127.8, 127.1, 126.8,
124.3, 121.4, 118.5, 117.9, 113.4, 55.1, 31.3, 31.0, 20.9, 15.3.
HRMS (ESI-TOF, m/z): calcd for C30H30N2NaO2S+, [M + Na]+,
505.1920, found 505.1920.
Reaction of unsaturated pyrazolones 1a with propargyl sulde
ylide 2b
5-(4-Bromophenyl)-1-(4-(methylthio)but-1-en-2-yl)-4-(1-
phenylvinyl)-2-(p-tolyl)-1,2-dihydro-3H-pyrazol-3-one (3aj)
To a ame-dried sealable 3-dram vial equipped with a stir bar
was added unsaturated pyrazolinones 1a (68 mg, 0.2 mmol, 1.0
The reaction was carried out on a 0.2 mmol scale following the equiv.), NaOAc$3H2O (14 mg, 0.1 mmol, 0.5 equiv.) and 2b
General procedure. The product 3aj was puried through (50 mg, 0.24 mmol, 1.2 equiv.) under air. Subsequently treated
column chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and CH3CN (2 mL, c ¼ 0.1 M) was added to vial via syringe. The
ꢀ
obtained as a foam solid (53 mg, 50% yield). IR nmax (neat)/ reaction mixture was stirred for 15 min at 20 C until unsatu-
1
cmꢁ1: 3039, 2962, 1670, 1527, 1363, 1299, 1108, 1036, 898; H rated pyrazolones 1a was fully consumed (monitored by TLC).
NMR (600 MHz, CDCl3): d 7.46 (d, J ¼ 8.4 Hz, 2H), 7.35 (d, J ¼ Then the reaction was stirred at 0 ꢀC for 20 h. The organic
8.4 Hz, 2H), 7.28–7.26 (m, 4H), 7.19–7.16 (m, 5H), 5.69 (s, 1H), solvent was removed under reduced pressure and puried
5.68 (s, 1H), 5.40 (s, 1H), 5.07 (s, 1H), 2.40 (s, 3H), 2.25 (t, J ¼ through column chromatography (eluent: petroleum ether and
7.8 Hz, 2H), 2.02 (t, J ¼ 7.8 Hz, 2H), 1.96 (s, 3H). 13C{1H} NMR EtOAc) to afford the desired product 4 (23% yield, 22 mg) and 5
(150 MHz, CDCl3): d 164.4, 153.7, 145.2, 140.3, 138.3, 136.6, (47% yield, 41 mg).
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chromatography (eluent: petroleum ether and EtOAc) to afford
the desired product 6 (36 mg, 62% yield, conversion: 74%).
1-(4-(Ethylthio)pent-1-en-2-yl)-2,5-diphenyl-4-(1-phenylvinyl)-
1,2-dihydro-3H-pyrazol-3-one (4)
IR nmax (neat)/cmꢁ1: 3082, 2977, 2864, 1705, 1594, 1466, 1272,
1
1042, 967, 832; H NMR (600 MHz, CDCl3): d 7.63 (dd, J ¼ 1.2,
1-(3-Methyl-4-(methylthio)but-1-en-2-yl)-2,5-diphenyl-4-(1-
phenylvinyl)-1,2-dihydro-3H-pyrazol-3-one (6)
8.4 Hz, 2H), 7.47 (t, J ¼ 7.8 Hz, 2H), 7.36 (d, J ¼ 8.4 Hz, 2H), 7.32–
7.25 (m, 4H), 7.22 (t, J ¼ 7.2 Hz, 2H), 7.17–7.11 (m, 3H), 5.69 (d, J
¼ 1.2 Hz, 1H), 5.63 (d, J ¼ 1.2 Hz, 1H), 5.52 (s, 1H), 5.09 (s, 1H),
2.64–2.59 (m, 1H), 2.41 (q, J ¼ 7.8 Hz, 2H), 2.19 (dd, J ¼ 4.8,
15.6 Hz, 1H), 1.77 (dd, J ¼ 9.6, 15.6 Hz, 1H), 1.18 (t, J ¼ 7.2 Hz,
3H), 0.78 (d, J ¼ 7.2 Hz, 1H); 13C{1H} NMR (150 MHz, CDCl3):
d 164.7, 155.6, 144.1, 140.3, 138.4, 136.2, 130.3, 129.7, 129.3,
128.7, 128.0, 127.9, 127.3, 127.0, 126.4, 124.2, 119.2, 118.9,
114.3, 39.2, 36.4, 24.6, 20.5, 14.7. HRMS (ESI-TOF, m/z): calcd for
The reaction was carried out on a 0.2 mmol scale following the
General procedure. The product 6 was puried through column
chromatography (PE/EtOAc: from 6 : 1 to 4 : 1) and obtained as
a foam solid (56 mg, 62% yield). IR nmax (neat)/cmꢁ1: 3062, 2933,
1668, 1574, 1379, 1259, 1149, 1028, 932, 834; 1H NMR (600 MHz,
CDCl3): d 7.63 (d, J ¼ 7.2 Hz, 2H), 7.47 (t, J ¼ 7.8 Hz, 2H), 7.36 (t, J
¼ 7.2 Hz, 2H), 7.32 (t, J ¼ 7.2 Hz, 2H), 7.29–7.22 (m, 4H), 7.17 (t, J
¼ 7.2 Hz, 2H), 7.13 (t, J ¼ 7.2 Hz, 1H), 5.68 (d, J ¼ 1.2 Hz, 1H),
5.60 (d, J ¼ 1.2 Hz, 1H), 5.51 (s, 1H), 5.10 (s, 1H), 2.19 (dd, J ¼
2.4, 13.2 Hz, 1H), 2.13–2.10 (m, 1H), 1.97 (dd, J ¼ 10.2, 13.2 Hz,
1H), 1.89 (s, 3H), 0.81 (d, J ¼ 6.6 Hz, 3H); 13C{1H} NMR (150
MHz, CDCl3): d 164.8, 155.6, 150.6, 140.3, 138.4, 136.2, 130.4,
129.6, 129.3, 128.7, 128.0, 127.9, 127.3, 126.9, 126.3, 124.1,
123.2, 118.8, 117.0, 114.0, 40.4, 35.1, 18.8, 15.9. HRMS (ESI-TOF,
m/z): calcd for C29H28N2NaOS+, [M + Na]+, 475.1815, found
475.1818.
C
30H30N2NaOS+, [M + Na]+, 489.1971, found 489.1972.
(E)-1-(1-(ethylthio)prop-1-en-2-yl)-2,5-diphenyl-4-(1-phenylvinyl)-
1,2-dihydro-3H-pyrazol-3-one (5)
IR nmax (neat)/cmꢁ1: 3057, 2973, 2824, 1698, 1572, 1376, 1269,
1187, 1028, 932; 1H NMR (600 MHz, CDCl3): d 7.58 (d, J ¼ 7.2 Hz,
2H), 7.46 (t, J ¼ 7.8 Hz, 2H), 7.33–7.30 (m, 5H), 7.26 (t, J ¼ 7.2 Hz,
1H), 7.21 (t, J ¼ 7.2 Hz, 2H), 7.16 (t, J ¼ 7.2 Hz, 2H), 7.12 (t, J ¼
7.2 Hz, 1H), 6.34 (s, 1H), 5.69 (d, J ¼ 1.2 Hz, 1H), 5.67 (d, J ¼
1.2 Hz, 1H), 2.53 (q, J ¼ 7.2 Hz, 2H), 1.38 (s, 3H), 1.03 (t, J ¼
7.2 Hz, 3H); 13C{1H} NMR (150 MHz, CDCl3): d 164.4, 155.5,
140.4, 138.6, 135.9, 133.3, 130.5, 129.8, 129.6, 129.5, 128.7,
127.9, 127.2, 127.1, 126.5, 124.7, 118.8, 114.8, 28.1, 15.4, 13.5.
HRMS (ESI-TOF, m/z): calcd for C28H27N2OS+, [M + H]+,
439.1839, found 439.1838.
Reaction of unsaturated pyrazolones 1d with methyl propargyl
sulde ylide 2d
To a ame-dried sealable 3-dram vial equipped with a stir bar
was added unsaturated pyrazolinones 1d (72 mg, 0.2 mmol, 1.0
equiv.), Cs2CO3 (33 mg, 0.1 mmol, 0.5 equiv.) under air.
Subsequently treated CH3CN (2 mL, c ¼ 0.1 M) was added to vial
via syringe. The reaction mixture was stirred for 2 h at 20 ꢀC
until unsaturated pyrazolones 1d was fully consumed (moni-
tored by TLC). Then the reaction was stirred at 0 ꢀC for 15 h. The
organic solvent was removed under reduced pressure and
puried through column chromatography (eluent: petroleum
ether and EtOAc) to afford the desired product 7 (65 mg, 68%
yield, conversion: 81%).
Reaction of unsaturated pyrazolones 1a with trimethylsilyl
propargyl sulde ylide 2c
To a ame-dried sealable 3-dram vial equipped with a stir bar
was added unsaturated pyrazolinones 1a (68 mg, 0.2 mmol, 1.0
equiv.), NaOAc$3H2O (14 mg, 0.1 mmol, 0.5 equiv.) and 2c
(61 mg, 0.24 mmol, 1.2 equiv.) under air. Subsequently treated
CH3CN (2 mL, c ¼ 0.1 M) was added to vial via syringe. The
ꢀ
reaction mixture was stirred for 15 min at 20 C until unsatu-
rated pyrazolones 1a was fully consumed (monitored by TLC).
Then the reaction was stirred at 0 ꢀC for 6 h. The organic solvent
was removed under reduced pressure and puried through
column chromatography (eluent: petroleum ether and EtOAc) to
afford the desired product 3a (79% yield, 70 mg).
4-(1-(4-Chlorophenyl)vinyl)-1-(3-methyl-4-(methylthio)but-
1-en-2-yl)-2,5-diphenyl-1,2-dihydro-3H-pyrazol-3-one (7)
The reaction was carried out on a 0.2 mmol scale. The product 7
was puried through column chromatography (PE/EtOAc: from
6 : 1 to 4 : 1) and obtained as a foam solid (64 mg, 66% yield). IR
nmax (neat)/cmꢁ1: 3086, 2982, 1688, 1559, 1437, 1322, 1251,
1067, 972, 853; 1H NMR (600 MHz, CDCl3): d 7.61 (d, J ¼ 7.8 Hz,
2H), 7.47 (t, J ¼ 7.8 Hz, 2H), 7.33 (d, J ¼ 7.2 Hz, 2H), 7.32–7.30
Reaction of unsaturated pyrazolones 1a with methyl propargyl
sulde ylide 2d
To a ame-dried sealable 3-dram vial equipped with a stir bar (m, 2H), 7.25 (d, J ¼ 7.2 Hz, 2H), 7.22 (t, J ¼ 7.2 Hz, 2H), 7.12 (d, J
was added unsaturated pyrazolinones 1a (68 mg, 0.2 mmol, 1.0 ¼ 8.4 Hz, 2H), 5.65 (s, 1H), 5.64 (s, 1H), 5.50 (s, 1H), 5.10 (s, 1H),
equiv.), Cs2CO3 (33 mg, 0.1 mmol, 0.5 equiv.) and 2d (47 mg, 2.18 (dd, J ¼ 1.8, 7.2 Hz, 1H), 2.12–2.08 (m, 1H), 1.97 (dd, J ¼
0.24 mmol, 1.2 equiv.) under air. Subsequently treated CH3CN 10.8, 13.2 Hz, 1H), 1.88 (s, 3H), 0.81 (t, J ¼ 6.6 Hz, 3H); 13C{1H}
(2 mL, c ¼ 0.1 M) was added to vial via syringe. The reaction NMR (150 MHz, CDCl3): d 164.5, 155.5, 150.4, 138.9, 137.4,
mixture was stirred for 2 h at 20 ꢀC until unsaturated pyr- 136.1, 133.2, 130.3, 129.8, 129.1, 128.8, 128.3, 128.1, 128.0,
azolones 1a was fully consumed (monitored by TLC). Then the 126.5, 124.1, 119.3, 117.1, 113.3, 40.4, 35.3, 18.7, 15.9. HRMS
reaction was stirred at 0 C for 15 h. The organic solvent was (ESI-TOF, m/z): calcd for C29H27ClN2NaOS+, [M + Na]+, 509.1425,
ꢀ
removed under reduced pressure and puried through column found 509.1425.
34922 | RSC Adv., 2019, 9, 34912–34925
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Gram-scale synthesis of 3a
Conflicts of interest
To a ame-dried sealable 3-dram vial equipped with a stir bar
was added unsaturated pyrazolinones 1a (1.01 g, 3.0 mmol, 1.0
equiv.), NaOAc$3H2O (204 mg, 1.5 mmol, 0.5 equiv.) and 2a
(0.65 g, 3.6 mmol, 1.2 equiv.) under air. Subsequently treated
CH3CN (25 mL, c ¼ 0.12 M) was added to vial via syringe. The
The authors declare no competing nancial interest.
Acknowledgements
ꢀ
reaction mixture was stirred for 20 min at 20 C until unsatu-
This work was supported by the research program from Natural
Science Foundation of Shanxi Province (201801D221067 and
201801D121048), the Natural Science Foundation of Shanxi
Normal University (0505/02080160 and 0109/01053018), and the
1331 Engineering of Shanxi Province. The instruments were
performed using the Analytical Test Center of Shanxi Normal
University, Linfen, China.
rated pyrazolones 1a was fully consumed (monitored by TLC).
Then the reaction was stirred at 0 ꢀC for 10 h. The organic
solvent was removed under reduced pressure and puried
through column chromatography (eluent: petroleum ether and
EtOAc) to afford the desired product 3a with a yield of 79% (1.01
g).
Oxidation of 3a with m-CPBA
References
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0.14 M). Aer stirred at 0 ꢀC for 10 min, m-CPBA (313 mg,
1.36 mmol, 75%, 2.0 equiv.) was added to the mixture slowly.
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1-(4-(Methylsulnyl)but-1-en-2-yl)-2,5-diphenyl-4-(1-phenylvinyl)-
1,2-dihydro-3H-pyrazol-3-one (8)
IR nmax (neat)/cmꢁ1: 3162, 2958, 1672, 1587, 1421, 1356, 1151,
1077, 946; 1H NMR (600 MHz, CDCl3): d 7.60 (d, J ¼ 7.8 Hz, 2H),
7.46 (t, J ¼ 7.2 Hz, 2H), 7.31 (d, J ¼ 7.2 Hz, 3H), 7.29–7.24 (m,
3H), 7.21 (t, J ¼ 7.2 Hz, 2H), 7.13 (t, J ¼ 7.2 Hz, 2H), 7.10 (t, J ¼
7.2 Hz, 1H), 5.68 (s, 2H), 5.52 (s, 1H), 5.11 (s, 1H), 2.41 (t, J ¼
6.6 Hz, 2H), 2.36 (s, 3H), 2.22 (t, J ¼ 6.6 Hz, 2H); 13C{1H} NMR
(150 MHz, CDCl3): d 164.6, 155.5, 143.9, 140.1, 138.2, 135.8,
129.9, 129.8, 128.8, 128.1, 128.0, 127.9, 127.2, 126.9, 126.5,
124.1, 119.1, 114.5, 51.5, 38.4, 23.9. HRMS (ESI-TOF, m/z): calcd
for C28H26N2NaO2S+, [M + Na]+, 477.1607, found 477.1609.
1-(4-(Methylsulfonyl)but-1-en-2-yl)-2,5-diphenyl-4-(1-phenylvinyl)-1,2-
dihydro-3H-pyrazol-3-one (9)
IR nmax (neat)/cmꢁ1: 3055, 2985, 1663, 1578, 1412, 1365, 1155,
1062, 964; 1H NMR (600 MHz, CDCl3): d 7.61 (d, J ¼ 1.2 Hz, 2H),
7.60 (d, J ¼ 1.2 Hz, 2H), 7.48 (t, J ¼ 7.8 Hz, 3H), 7.34–7.27 (m,
3H), 7.23 (t, J ¼ 7.2 Hz, 2H), 7.15 (t, J ¼ 7.2 Hz, 2H), 7.12 (t, J ¼
7.2 Hz, 1H), 5.70 (s, 2H), 5.54 (s, 1H), 5.09 (d, J ¼ 0.6 Hz, 1H),
2.73 (t, J ¼ 8.4 Hz, 2H), 2.68 (s, 3H), 2.29 (t, J ¼ 8.4 Hz, 2H); 13
C
{1H} NMR (150 MHz, CDCl3): d 164.7, 155.5, 143.2, 140.1, 138.1,
135.8, 130.0, 129.0, 128.2, 128.0, 127.4, 127.0, 126.8, 124.1,
119.3, 115.1, 52.4, 40.5, 24.0. HRMS (ESI-TOF, m/z): calcd for
C
28H26N2NaO3S+, [M + Na]+, 493.1556, found 493.1558.
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