Palladium N-heterocyclic carbene catalyzed regioselective C-H halogenation of 1-aryl-3-methyl-1H-pyrazol-5(4H)-ones using N-halosuccinimides (NXS)

Article abstract of DOI:10.1039/c5cy00137d

A novel palladium N-heterocyclic carbene [Pd(NHC)Cl₂] complex of vitamin B₁ was synthesized and characterized by ¹H NMR, EDX, FT-IR and UV-visible spectroscopy. The complex was used as a catalyst for regioselective ortho-C-H chlorination/bromination of 1-aryl-3-methyl-1H-pyrazol-5(4H)-ones via C-H bond activation utilizing Ag₂O as the effective terminal additive. The catalyst was easy to prepare, efficient and found to be highly regioselective, affording the target products in moderate to excellent yields.

Full text of DOI:10.1039/c5cy00137d

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DOI: 10.1039/C5CY00137D
Journal Name
RSCPublishing
ARTICLE
Palladium N-heterocyclic carbene catalyzed
regioselective C-H halogenation of 1-Aryl-3-
Cite this: DOI: 10.1039/x0xx00000x
methyl-1H-pyrazol-5(4H)-ones
halosuccinimides (NXS)
using
N-
Received 00th January 2012,
Accepted 00th January 2012
DOI: 10.1039/x0xx00000x
Vishal B. Purohit*, Sharad C. Karad, Kirit H. Patel, Dipak K. Raval
www.rsc.org/
A novel palladium N-heterocyclic carbene [Pd(NHC)Cl2] complex of Vitamin B1 was synthesized and
characterized by 1H NMR, EDX, FT-IR and UV−visible spectroscopy. The complex was used as a catalyst
for the regioselective ortho- C–H chlorination/bromination of 1-Aryl-3-methyl-1H-pyrazol-5(4H)-ones via
C-H bond activation utilizing Ag2O as the effective terminal additive. The catalyst was easy to prepare,
efficient and was found to be highly regioselective to afford the target products in moderate to
excellent yield.
not been reported yet. The pyrazolꢀ5(4H)ꢀone fragment in 1a
1. Introduction
acts as the intrinsic directing group.
Recently, palladiumꢀcatalyzed functionalization of C−H bonds
has emerged as a valuable, atomꢀ and stepꢀeconomical tool to
construct C−C and C−heteroatom (O, N, Cl, Br, I) bonds
proximal to the directing group with high regioselectivity.1
Synthetic efforts have focused on several CꢀH activation
reactions including arylation,2 olefination,3 oxygenation,4
amination,5 phosphonation,6 sulfonylation7 and halogenations8
of both sp2 and sp3 CꢀH bonds. Amongst them, Pdꢀcatalyzed
selective orthoꢀsp2 CꢀH halogenation reactions8 have drawn
much interest because aromatic halides are extremely valuable
intermediates for synthetic elaboration.
Since the seminal discovery of first Nꢀheterocyclic carbene
(NHC) by Arduengo,12 NHCꢀtransition metal complexes have
attracted considerable attention in the fields of organometallic
chemistry and catalysis.13 Due to strong σꢀdonating and little
πꢀ
back bonding ability to stabilize the complexes, NHCs can
generally be seen as alternatives to the widely used phosphine
ligands.14 Various complexes of palladium with NHC ligands
have been prepared for coupling reactions.15 Notably, all the
pioneering work was limited to imidazolium based NHC
ligands which were toxic, poorly biodegradable16 and
complicated to synthesize through multiple steps.17 Various
complexes of Pd(II) with NHC ligands have been prepared for
Significant efforts have been made for selective orthoꢀ
halogenation of sp2 CꢀH bonds by exploiting directing groups
such as pyridines,8a cyano,8d aryl azo,8e acylaminos,9 oxime
ethers,8c carbamates10 and various Nꢀheterocycles. In some
cases, the directing group needs to be preꢀbuiltꢀin and then
removed afterwards.8c 3ꢀMethylꢀ1ꢀphenylꢀ1Hꢀpyrazolꢀ5(4H)ꢀ
one 1a itself is a neuroprotective drug known as Edaravone11
which is used for the treatment of patients in acute stage of
cerebral infarction brain ischemia. Therefore, our present study
on C–H halogenations of compound 1a will not only lead to a
new regioselective protocol, but also provides new analogues of
the existing drug 1a for immediate drug screening. To the best
of our knowledge, Pdꢀcatalyzed C–H halogenation of 1a has
Scheme 1. Catalyst effect on ortho/para-halogenation selectivity
coupling reactions.18 By taking the advantage of thiamine
hydrochloride (VB1) over imidazolium NHC ligands, recently
we have synthesized
a
novel copper(Nꢀheterocyclic
This journal is © The Royal Society of Chemistry 2013
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DOI: 10.1039/C5CY00137D
carbene)chloride [Cu(NHC)Cl] complex of Vitamin B1 for 2.2 Optimization of reaction conditions
three component click reaction.19
Initially, the optimization of the reaction conditions for
Pd(NHC)Cl2 catalyzed halogenation was carried out using 3ꢀ
methylꢀ1ꢀphenylꢀ1Hꢀpyrazolꢀ5(4H)ꢀone 1a as a model substrate
with Nꢀchlorosuccinimide (NCS) as a halogen source in
presence of NHC, various additives and solvents. The reaction
proceeded smoothly to give desired product 2a in good to
moderate yields with exclusive orthoꢀselectivity. It was
surprisingly noted that in absence of the Pd catalyst, a mixture
of orhtoꢀ (2a) and paraꢀchloro (2a’) products were formed in
very poor yields (Scheme 1). Two such bromo derivatives were
obtained with NBS as the halogen source. The effectiveness of
the model reaction was tested against various Pdꢀsources (Table
1). Among them, Pd(NHC)Cl2 was found to be the most
effective over other palladium species such as Pd(OAc)2, PdCl2
and Pd(PPh3)4. 5 mol % catalyst loading was observed to give
the product 2a in 77 % yield (Table 1, entry 3). To investigate
the effects of solvent, the model reaction was performed in
various solvents at 80 ºC using 5 mol % Pd(NHC)Cl2 as the
catalyst and 0.5 mmol of different additives (Table 2). It was
observed that MeCN showed clearcut advantage over the other
organic solvents having 77 % yields of 2a (Table 2, entry 6) in
8 h. In order to improve the yield, effect of some additives such
as Ag2O, Ag2SO4, Ag2CO3, K2S2O8 and oxone was checked
(Table 2). In absence of any added additives only 36 % yield of
2a was obtained (Table 2, entry 1) but the presence of 0.5 mmol
Ag2O improved the yield of 2a up to 77 % (Table 2, entry 6).
Thus, the optimized reaction condition was set as 5 mol % of
Pd(NHC)Cl2 as the catalyst with Ag2O as an additive in MeCN
at 80 ºC using 1 mmol of 1ꢀarylpyrazolone and 1.1 mmol of
NXS.
In continuation to our previous efforts,19ꢀ20, 22 herein we report
first ever synthesis and characterization of novel Pd(NHC)Cl2
complex of Vitamin B1 and its catalytic application for the
regioselective C–H halogenations (Cl, Br) of 3ꢀmethylꢀ1ꢀarylꢀ
1Hꢀpyrazolꢀ5(4H)ꢀones using
Nꢀhalosuccinimides (NXS). The
protocol was found to be simple, efficient and highly
regioselective to afford the target products in moderate to
excellent yield.
2. Results and discussion
2.1 Characterization of catalyst.
The synthesized Pd(NHC)Cl2 catalyst was thoroughly
characterized by 1H NMR, FTꢀIR, EDX and UV−visible
spectroscopy. FTꢀIR spectrum of the catalyst exhibited
absorption bands at 1620 (C=N stretch) and 3630 cmꢀ1 (OH
stretch). The characteristic amino stretching vibration bands
were observed at 3340 and 3315 cmꢀ1. NꢀH bending absorption
appeared at 1665 cmꢀ1. The EDX spectrum for the catalyst
showed the existence of sulphur, chlorine and palladium
elements (Figure 1) and confirmed the weight % of C, N, O, S,
Pd and Cl respectively as 31.06, 13.06, 2.92, 8.31, 25.41 and
17.23 as expected with the calculated values of 32.56, 12.66,
3.61, 7.24, 24.04 and 16.02. The UV−visible spectra of free
NHC ligand and the catalyst in distilled DMSO exhibited
absorption bands at 268 and 275 nm respectively (Figure 2).
The bathochromic shift in absorption spectrum may be assigned
to complexation of NHC ligand with palladium.
Table 2. Optimization of the reaction conditions for the synthesisa of 2a
Timeb (h)
Entry
1
2
3
4
5
6
7
8
Additive
ꢀ
Solvent
MeCN
Toluene
DMF
Dioxane
AcOH
MeCN
MeCN
MeCN
MeCN
MeCN
Yieldc (%)
12
8
8
8
8
36
40
36
25
70
77
62
60
36
42
Ag2O
Ag2O
Ag2O
Ag2O
Ag2O
Ag2SO4
Ag2CO3
K2S2O8
Oxone
8
10
10
10
10
9
10
aReaction conditions: 3ꢀMethylꢀ1ꢀphenylꢀ1Hꢀpyrazolꢀ5(4H)ꢀone (1 mmol),
NCS (1.1 mmol), Ag2O (0.5 mmol) Pd(NHC)Cl2 (5 mol %), solvent (2 mL)
Figure 1. EDX analysis of Pd(NHC)Cl2
b
and 80 ºC. All the reactions were monitored by TLC using hexane : ethyl
Table 1. Catalyst screening for the synthesisa 2a
acetate (1:1). cIsolated yield.
Entry
Catalyst
Nil
Pd(NHC)Cl2
Pd(NHC)Cl2
Pd(OAc)2
PdCl2
mol %
Timeb (h)
Yieldc (%)
Based on previous studies, the mechanistic investigation of
Pd(NHC)Cl2 catalyzed regioselective CꢀH halogenation of 1a
has been assumed to involve a Pd(II) – Pd(IV) catalytic cycle.8c,
21 Although, the role of Ag2O was seemed to be very crucial. It
might have acted as an oxidant or a coꢀcatalyst. The plausible
mechanism is suggested in Scheme 2. Ag2O may oxidize the
1
2
3
4
5
6
ꢀ
10
5
5
5
12
8
8
10
9
8
n.d.
77
77
71
69
60
Pd(PPh3)4
5
aReaction conditions: 3ꢀMethylꢀ1ꢀphenylꢀ1Hꢀpyrazolꢀ5(4H)ꢀone (1 mmol),
NCS (1.1 mmol), Ag2O (0.5 mmol) Pdꢀ catalyst (5 mol %), acetonitrile (2
mL) and 80 ºC. bAll the reactions were monitored by TLC using hexane :
ethyl acetate (1:1). cIsolated yield, n.d., not detected.
orthoꢀ CꢀH bond of 1a to form the intermediate
A. A may then
undergo transmetallation with Pd(NHC)Cl2 to yield Pd(II)
complex
B, which after oxidative addition of NXS forms a
2 | J. Name., 2012, 00, 1-3
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ARTICLE
DOI: 10.1039/C5CY00137D
Pd(IV) intermediate
C
. Finally, halogenated product 2a (or 3a
)
3ꢀmethylꢀ1Hꢀpyrazolꢀ5(4H)ꢀones utilizing Nꢀhalosuccinimide
is obtained via reductive elimination of
regeneration of the Pd(II) catalyst.
C
, followed by as the halogenating reagent and Ag2O as the effective additive
via C−H bond activation. The protocol was found to be simple,
efficient and highly regioselective to afford the target products
in moderate to excellent yield. Moreover, the present study had
not only led to the regioselectivity, but also provided valuable
synthetic building blocks in organic synthesis.
Figure 2. UV−visible spectra of free NHC ligand and catalyst.
Table 3. Pd(NHC)Cl2 catalyzed regioselective CꢀH halogenation of 1ꢀArylꢀ3ꢀ
methylꢀ1Hꢀpyrazolꢀ5(4H)ꢀonesa 1a-d.
Scheme 2. Plausible catalytic cycle for the regioselective C-H halogenation of 3-
Methyl-1-phenyl-1H-pyrazol-5(4H)-one.
4. Experimental section
All the chemicals were purchased from Sigma Aldrich and used
as received. All organic solvents used were of analytical grade
and used without further purification. All the reactions were
monitored by thinꢀlayer chromatography carried out on
fluorescent coated plates (aluminium plates coated with silica
gel 60 F254, 0.25 mm thickness, Merck) and detection of the
components was made by exposure to UV light. NMR spectra
were recorded in CDCl3 on Bruker Avance 400 MHz
Entry
Compounds
R
R1
X
Timeb
(h)
8
8.5
8.5
9
8
8.5
9
Yieldc
(%)
77
75
70
73
76
72
72
1
2
4
3
5
6
8
7
2a
2b
2c
2d
3a
3b
3c
3d
ꢀH
ꢀCl
ꢀH
ꢀH
ꢀH
ꢀCl
ꢀH
ꢀH
ꢀH
ꢀH
ꢀCH3
ꢀCl
ꢀH
ꢀH
ꢀCl
ꢀCl
ꢀCl
ꢀCl
ꢀBr
ꢀBr
ꢀBr
ꢀBr
spectrometer. The chemical shifts are reported in
ꢀ parts per
million. IR spectra were recorded on a FTIR PerkinElmer
Spectrum 100 spectrometer in KBr pellets with absorption in
cm−1 at Sophisticated Instrumentation Centre for Applied
ꢀCH3
ꢀCl
9
74
Research
&
Training (SICART), Vallabh Vidyanagar.
aReaction conditions: 1ꢀarylpyrazolones (1 mmol), NXS (X = Cl or Br, 1.1
mmol), Ag2O (0.5 mmol) Pd(NHC)Cl2 (5 mol %), acetonitrile (2 mL) and 80
Elemental analysis was performed on PerkinElmer 2400 seriesꢀ
II elemental analyzer (PerkinElmer, USA) and all results are
b
ºC. All the reactions were monitored by TLC using hexane : ethyl acetate
found within
Ə0.4% of the theoretical compositions. IKA RV
c
(1:1). Isolated yield.
10 control rotary evaporator was used to distill the solvents
under vacuum. The EDX was performed using JOEL JSMꢀ
5610 scanning electron microscope (SEM).
With the optimized reaction conditions in hand, a scope of the
Pd(NHC)Cl2 catalyzed regioselective CꢀH halogenation
reaction was investigated with a diverse array of substituted 1ꢀ
Arylꢀ3ꢀmethylꢀ1Hꢀpyrazolꢀ5(4H)ꢀones 1a-d (Table 3). The
substrates bearing electronꢀdonating or –withdrawing
substituents on the aryl ring reacted smoothly to afford the
desired products in good to moderate yields. All the results are
summarized in Table 3. The structures of all the synthesized
compounds were well characterized by NMR spectroscopy.
4.1 Synthesis of palladium N-heterocyclic carbene complex
A 50 mL round bottom flask was charged with Pd(OAc)2 (0.5
mmol), thiamine hydrochloride (vitamin B1) (1 mmol), NaOtꢀ
Bu (1 mmol) and THF (5 mL). The mixture was stirred at room
temperature for 3 h and then refluxed for additional 2 h. After
cooling to room temperature, the resulting orange residue was
filtered, washed with acetonitrile (2 × 5 mL) and dried under
vacuum to afford the title compound with 80% yield.
3. Conclusion
1H NMR (400 MHz, DMSOꢀd6): δ (ppm) 2.39 (s, 3H), 2.51(s,
3H), 3.05 (t, 2H), 3.65 (t, 2H), 5.47 (s, 2H), 7.40 (s, 2H), 8.11
A novel Pd(NHC)Cl2 catalyst has been developed for the
regioselective orthoꢀ C–H chlorination/ bromination of 1ꢀArylꢀ
This journal is © The Royal Society of Chemistry 2012
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VJieowuArrtnicalelONnlainme e
ARTICLE
DOI: 10.1039/C5CY00137D
(s, 1H), 9.60 (s, 1H). FTꢀIR (KBr): 3630, 3410, 3340, 3315, C10H8Cl2N2O: C, 49.41; H, 3.32; N, 11.52. Found: C, 49.31; H,
3100, 1620, 1430, 1527, 1060, 780, 610 cmꢀ1
3.17; N, 11.30.
4.2 General procedure for the regioselective halogenation of 1-
Aryl-3-methyl-1H-pyrazol-5(4H)-ones catalyzed by Pd(NHC)Cl2
4.3.5 1-(2-bromophenyl)-3-methyl-1H-pyrazol-5(4H)-one (3a)
1H NMR (400 MHz, CDCl3): δ (ppm) 2.22 (s, 3H), 3.46 (s,
2H), 7.15ꢀ7.18 (m, 1H), 7.32 (t, 1H), 7.83ꢀ7.86 (m, 1H), 7.95 (t,
1H), 13C NMR (100 MHz, CDCl3): δ (ppm) 17.02 (CH3), 43.12
(CH2), 116.47, 118.62, 124.87, 129.88, 134.57, 139.09, 156.63
(C=N), 170.53 (C=O), FTꢀIR (KBr): 3110, 2813, 1625 (C=O
str.), 1580 (C=N str.), 1480, 1318, 1215, 1031, 969 cmꢀ1, Anal.
Calcd. for C10H9BrN2O: C, 47.46; H, 3.58; N, 11.07. Found: C,
47.40; H, 3.42; N, 10.98.
A mixture of 1ꢀArylꢀ3ꢀmethylꢀ1Hꢀpyrazolꢀ5(4H)ꢀones (1 mmol),
NXS (X = Cl or Br, 1.1 mmol), Ag2O (0.5 mmol) and
Pd(NHC)Cl2 complex (5 mol %) in 2 mL acetonitrile was
magnetically stirred at 80 ºC for the required time. The solvent
was removed under vacuum and the resulting residues were
purified by chromatography on silica gel column by using
hexane : ethyl acetate (20 : 1, v/v) as eluent to afford the
desired products
.
4.3.6 1-(2-bromo-5-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-
one (3b)
1H NMR (400 MHz, CDCl3): δ (ppm) 2.20 (s, 3H), 3.43 (s,
2H), 7.31 (dd, J = 2.4, Hz, J
= 8.8 Hz, 1H), 7.44 (t, 2H), 13C
4.3 Spectral data
4.3.1 1-(2-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (2a)
1H NMR (400 MHz, CDCl3): δ (ppm) 2.21 (s, 3H), 3.44 (s,
2H), 7.33ꢀ7.38 (m, 2H), 7.42ꢀ7.45 (m, 1H), 7.51ꢀ7.53 (m, 1H),
13C NMR (100 MHz, CDCl3): δ (ppm) 17.15 (CH3), 41.47
(CH2), 127.56, 128.85, 129.85, 130.56, 131.82, 134.44, 156.60
(C=N), 171.26 (C=O), FTꢀIR (KBr): 3104, 2810, 1623 (C=O
str.), 1585 (C=N str.), 1494, 1311, 1218, 1035, 964 cmꢀ1, Anal.
Calcd. for C10H9ClN2O: C, 57.57; H, 4.35; N, 13.43. Found: C,
57.49; H, 4.26; N, 13.40.
NMR (100 MHz, CDCl3): δ (ppm) 17.15 (CH3), 41.42 (CH2),
120.00, 128.67, 129.74, 129.98, 131.35, 135.35, 157.06 (C=N),
170.96 (C=O), FTꢀIR (KBr): 3107, 2811, 1625 (C=O str.), 1582
(C=N str.), 1481, 1315, 1214, 1030, 969 cmꢀ1, Anal. Calcd. for
C10H8BrClN2O: C, 41.77; H, 2.80; N, 9.74. Found: C, 41.57; H,
2.71; N, 9.55.
4.3.7 1-(2-bromo-4-methylphenyl)-3-methyl-1H-pyrazol-5(4H)-
one (3c)
1H NMR (400 MHz, CDCl3): δ (ppm) 2.21 (s, 3H), 2.36 (s,
4.3.2 1-(2,5-dichlorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (2b)
1H NMR (400 MHz, CDCl3): δ (ppm) 2.21 (s, 3H), 3.43 (s,
2H), 7.31 (dd, J = 2.8 Hz, J
= 8.4 Hz, 1H), 7.45 (t, 2H), 13C
3H), 3.44 (s, 2H), 7.18ꢀ7.27 (m, 2H), 7.74 (d,
J = 4.4 Hz, 1H),
13C NMR (100 MHz, CDCl3): δ (ppm) 17.04 (CH3), 20.96(Arꢀ
CH3), 43.07 (CH2), 128.67, 119.00, 120.90, 129.35, 134.77,
134.78, 135.60, 156.15 (C=N), 170.44 (C=O), FTꢀIR (KBr):
3108, 2810, 1622 (C=O str.), 1585 (C=N str.), 1480, 1315,
1212, 1030, 967 cmꢀ1, Anal. Calcd. for C11H11BrN2O: C, 49.46;
H, 4.15; N, 10.49. Found: C, 49.41; H, 3.97; N, 10.34.
NMR (100 MHz, CDCl3): δ (ppm) 17.15 (CH3), 41.42 (CH2),
128.67, 129.74, 129.98, 131.35, 132.95, 135.36, 157.04 (C=N),
170.95 (C=O), FTꢀIR (KBr): 3101, 2810, 1629 (C=O str.), 1582
(C=N str.), 1489, 1308, 1210, 1032, 967 cmꢀ1, Anal. Calcd. for
C10H8Cl2N2O: C, 49.41; H, 3.32; N, 11.52. Found: C, 49.39; H,
3.18; N, 11.36.
4.3.8 1-(2-bromo-4-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-
one (3d)
1H NMR (400 MHz, CDCl3): δ (ppm) 2.21 (s, 3H), 3.43 (s,
2H), 7.33 (dd, J = 2.4, Hz, J
= 8.8 Hz, 1H), 7.44 (t, 2H), 13C
4.3.3 1-(2-chloro-4-methylphenyl)-3-methyl-1H-pyrazol-5(4H)-
one (2c)
1H NMR (400 MHz, CDCl3): δ (ppm) 2.21 (s, 3H), 2.36 (s,
NMR (100 MHz, CDCl3): δ (ppm) 16.22 (CH3), 44.51 (CH2),
116.57, 123.42, 130.06, 134.46, 145.01, 157.04 (C=N), 169.26
(C=O), FTꢀIR (KBr): 3102, 2810, 1625 (C=O str.), 1585 (C=N
str.), 14804, 1314, 1210, 1032, 968 cmꢀ1, Anal. Calcd. for
C10H8BrClN2O: C, 41.77; H, 2.80; N, 9.74. Found: C, 41.67; H,
2.69; N, 9.65.
3H), 3.44 (s, 2H), 7.28ꢀ7.35 (m, 2H), 7.73 (d,
J = 3.6 Hz, 1H),
13C NMR (100 MHz, CDCl3): δ (ppm) 17.05 (CH3), 20.97(Arꢀ
CH3), 43.08 (CH2), 128.67, 119.00, 126.06, 129.36, 134.78,
135.59, 145.10, 156.17 (C=N), 170.45 (C=O), FTꢀIR (KBr):
3107, 2810, 1625 (C=O str.), 1580 (C=N str.), 1484, 1315,
1214, 1032, 969 cmꢀ1, Anal. Calcd. for C11H11ClN2O: C, 59.33;
H, 4.98; N, 12.58. Found: C, 59.22; H, 4.72; N, 12.35
4.3.9 1-(4-chlorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (2a’)
1H NMR (400 MHz, CDCl3): δ (ppm) 2.22 (s, 3H), 3.46 (s,
4.3.4 1-(2,4-dichlorophenyl)-3-methyl-1H-pyrazol-5(4H)-one (2d)
1H NMR (400 MHz, CDCl3): δ (ppm) 2.19 (s, 3H), 3.50 (s,
2H), 7.98 (t, 1H), 8.33 (m, 1H), 9.15 (d, J
= 2.4 Hz, 1H), 13C
2H), 7.36
(dd, J = 2.4, Hz, J = 7.2 Hz, 2H), 7.86 (dd, J = 2.0,
Hz,
J
= 6.8 Hz, 2H), 13C NMR (100 MHz, CDCl3): δ (ppm)
17.06 (CH3), 43.10 (CH2), 119.87, 128.87, 131.59, 135.99,
156.19 (C=N), 170.45 (C=O), FTꢀIR (KBr): FTꢀIR (KBr):
3110, 2815, 1620 (C=O str.), 1582 (C=N str.), 1486, 1315,
1210, 1032, 966 cmꢀ1, Anal. Calcd. for C10H9ClN2O: C, 57.57;
H, 4.35; N, 13.43. Found: C, 57.51; H, 4.22; N, 13.13.
NMR (100 MHz, CDCl3): δ (ppm) 17.15 (CH3), 41.42 (CH2),
128.68, 129.76, 129.98, 131.35, 132.95, 135.36, 157.04 (C=N),
170.95 (C=O), FTꢀIR (KBr): 3109, 2811, 1629 (C=O str.), 1583
(C=N str.), 1485, 1320, 1213, 1035, 967 cmꢀ1, Anal. Calcd. for
4 | J. Name., 2012, 00, 1-3
This journal is © The Royal Society of Chemistry 2012

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Journal Name
Catalysis Science & Technology
View ArticAle ROnTliInCeLE
DOI: 10.1039/C5CY00137D
4.3.10 1-(4-bromophenyl)-3-methyl-1H-pyrazol-5(4H)-one (3a’)
Fossey, T. Cailly, S. Rault and F. Fabis, J. Org. Chem., 2011, 76,
6414; (d) B. Du, X. Jiang and P. Sun, J. Org. Chem., 2013, 78, 2786;
(e) X.ꢀT. Ma and S.ꢀK. Tian, Adv. Synth. Catal., 2013, 355, 337; (f)
1H NMR (400 MHz, CDCl3): δ (ppm) 2.22 (s, 3H), 3.45 (s,
2H), 7.49ꢀ7.53 (m, 2H), 7.79ꢀ7.83 (
m, 2H), 13C NMR (100
P. Sadhu, S. K. Alla and T. Punniyamurthy, J. Org. Chem., 2013, 78
6104; (g) X. Sun, Y. Sun, C. Zhang and Y. Rao, Chem. Commun.
2014, 50, 1262.
,
MHz, CDCl3): δ (ppm) 17.07 (CH3), 43.12 (CH2), 119.00,
120.16, 131.82, 138.22, 156.04 (C=N), 170.94 (C=O), FTꢀIR
(KBr): 3105, 2811, 1625 (C=O str.), 1583 (C=N str.), 1490,
1310, 1218, 1035, 967 cmꢀ1, Anal. Calcd. for C10H9BrN2O: C,
47.46; H, 3.58; N, 11.07. Found: C, 47.33; H, 3.41; N, 10.91.
,
9. R. B. Bedford, M. F. Haddow, C. J. Mitchell and R. L. Webster,
Angew. Chem. Int. Ed., 2011, 50, 5524.
10. A. John and K. M. Nicholas, J. Org. Chem., 2012, 77, 5600.
11. (a) R. Tabrizchi, Current opinion in investigational drugs (London,
Acknowledgements
England: 2000), 2000, 1, 347; (b) Y.ꢀJ. Jin, T. Mima, V. Raicu, K. C.
VBP and SCK wish to acknowledge University Grants
Commission–New Delhi, India for UGC Basic Scientific
Research Fellowship awarded to them during 2013ꢀ2015. The
authors are thankful to Head, Department of Chemistry, Sardar
Patel University for providing necessary research facilities. The
authors also thankful to Dr. V. S. Patel, Director, SICART,
Vallabh Vidyanagarꢀ388 120, India for elemental analysis at
concessional rates.
Park and K. Shimizu, Neuroscience research, 2002, 43, 75; (c)
Cerebrovascular Diseases, 2003, 15, 222; (d) T. Watanabe, M.
Tahara and S. Todo, Cardiovascular Therapeutics, 2008, 26, 101.
12. A. J. Arduengo, R. L. Harlow and M. Kline, J. Am. Chem. Soc., 1991,
113, 361.
13. (a) S. DíezꢀGonzález, N. Marion and S. P. Nolan, Chem. Rev., 2009,
109, 3612; (b) S. Roy and H. Plenio, Adv. Synth. Catal., 2010, 352
,
1014.
14. (a) A. A. Danopoulos, D. Pugh, H. Smith and J. Saßmannshausen,
Chemistry – A European Journal, 2009, 15, 5491; (b) H. D.
Velazquez and F. Verpoort, Chem. Soc. Rev., 2012, 41, 7032.
Notes
Department of Chemistry, Sardar Patel University, Vallabh
Vidyanagarꢀ 388 120, Gujarat, India.
*Corresponding author. Tel.: +91ꢀ02692ꢀ226856 ꢀ Ext. ꢀ 211;
Fax: +91ꢀ02692 236475.
Eꢀmail: vishalpurohit113@gmail.com; dipanalka@yahoo.com
The spectral data of synthesized compound are shown in
supplementary data.
15. (a) N. Miyaura and A. Suzuki, Chem. Rev., 1995, 95, 2457; (b) G. C.
Fortman and S. P. Nolan, Chem. Soc. Rev., 2011, 40, 5151.
16. (a) R. P. Swatloski, J. D. Holbrey and R. D. Rogers, Green Chem.
2003, , 361; (b) M. T. Garcia, N. Gathergood and P. J. Scammells,
Green Chem., 2005, , 9; (c) D. Zhao, Y. Liao and Z. Zhang, CLEAN
– Soil, Air, Water, 2007, 35, 42; (d) M. A. P. Martins, C. P. Frizzo, D.
,
5
7
N. Moreira, N. Zanatta and H. G. Bonacorso, Chem. Rev., 2008, 108
,
2015.
References
17. (a) L. Jafarpour, E. D. Stevens and S. P. Nolan, J. Organomet.
Chem., 2000, 606, 49; (b) C. Fleckenstein, S. Roy, Leuthau and H.
Plenio, Chem. Commun., 2007, 2870; (c) L. Li, J. Wang, C. Zhou, R.
Wang and M. Hong, Green Chem., 2011, 13, 2071.
1. (a) X. Chen, K. M. Engle, D.ꢀH. Wang and J.ꢀQ. Yu, Angew. Chem.
Int. Ed., 2009, 48, 5094; (b) T. W. Lyons and M. S. Sanford, Chem.
Rev., 2010, 110, 1147; (c) C. S. Yeung and V. M. Dong, Chem. Rev.
,
18. X. Bantreil, J. Broggi and S. P. Nolan, Annual Reports Section "B"
(Organic Chemistry), 2009, 105, 232.
2011, 111, 1215; (d) K. M. Engle, T.ꢀS. Mei, M. Wasa and J.ꢀQ. Yu,
Acc. Chem. Res., 2011, 45, 788.
19. V. B. Purohit, S. C. Karad, K. H. Patel and D. K. Raval, RSC Adv.
2014, , 46002.
,
2. (a) N. Kuhl, M. N. Hopkinson, J. WencelꢀDelord and F. Glorius,
Angew. Chem. Int. Ed., 2012, 51, 10236; (b) D.ꢀD. Li, T.ꢀT. Yuan
and G.ꢀW. Wang, J. Org. Chem., 2012, 77, 3341.
4
20. (a) J. R. Avalani, D. S. Patel and D. K. Raval, J. Mol. Catal. B:
Enzym., 2013, 90, 70; (b) S. P. Satasia, P. N. Kalaria and D. K. Raval,
3. (a) L. Liu, H. Yuan, T. Fu, T. Wang, X. Gao, Z. Zeng, J. Zhu and Y.
Zhao, J. Org. Chem., 2014, 79, 80; (b) C. Zhang, J. Ji and P. Sun, J.
Org. Chem., 2014, 79, 3200.
RSC Adv., 2013,
3, 3184; (c) P. N. Kalaria, J. A. Makawana, S. P.
Satasia, D. K. Raval and H.ꢀL. Zhu, MedChemComm, 2014,
5, 1555;
(d) P. N. Kalaria, S. P. Satasia, J. R. Avalani and D. K. Raval, Eur. J.
Med. Chem., 2014, 83, 655; (e) P. N. Kalaria, S. P. Satasia and D. K.
4. (a) M. H. Emmert, A. K. Cook, Y. J. Xie and M. S. Sanford, Angew.
Chem. Int. Ed., 2011, 50, 9409; (b) P. Novák, A. Correa, J. Gallardoꢀ
Donaire and R. Martin, Angew. Chem. Int. Ed., 2011, 50, 12236.
Raval, RSC Adv., 2014, 4, 32353; (f) P. N. Kalaria, S. P. Satasia and
D. K. Raval, New J. Chem., 2014, 38, 1512; (g) P. N. Kalaria, S. P.
Satasia and D. K. Raval, New J. Chem., 2014, 38, 2902; (h) P. N.
5. (a) W. C. P. Tsang, N. Zheng and S. L. Buchwald, J. Am. Chem. Soc.
,
2005, 127, 14560; (b) H.ꢀY. Thu, W.ꢀY. Yu and C.ꢀM. Che, J. Am.
Chem. Soc., 2006, 128, 9048.
Kalaria, S. P. Satasia and D. K. Raval, Eur. J. Med. Chem., 2014, 78
,
207; (i) S. C. Karad, V. B. Purohit and D. K. Raval, Eur. J. Med.
Chem., 2014, 84, 51; (j) S. P. Satasia, P. N. Kalaria, J. R. Avalani and
D. K. Raval, Tetrahedron, 2014, 70, 5763; (k) S. P. Satasia, P. N.
Kalaria and D. K. Raval, Org. biomol. chem., 2014, 12, 1751; (l) S. P.
6. C. Li, T. Yano, N. Ishida and M. Murakami, Angew. Chem. Int. Ed.
,
2013, 52, 9801.
7. X. Zhao, E. Dimitrijević and V. M. Dong, J. Am. Chem. Soc., 2009,
131, 3466.
Satasia, P. N. Kalaria and D. K. Raval, J. Mol. Catal. A: Chem.
,
8. (a) D. Kalyani, A. R. Dick, W. Q. Anani and M. S. Sanford,
Tetrahedron, 2006, 62, 11483; (b) D. Kalyani, A. R. Dick, W. Q.
2014, 391, 41.
21. L.ꢀM. Xu, B.ꢀJ. Li, Z. Yang and Z.ꢀJ. Shi, Chem. Soc. Rev., 2010, 39
,
Anani and M. S. Sanford, Org. Lett., 2006, 8, 2523; (c) E. Dubost, C.
712.
This journal is © The Royal Society of Chemistry 2012
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DOI: 10.1039/C5CY00137D
22. S. C. Karad, V. B. Purohit, D. K. Raval, P. N. Kalaria, J. R. Avalani,
P. Thakor and V. R. Thakkar, RSC Adv., 2015, , 16000
5
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