Copper on iron promoted one-pot synthesis of β-aminoenones and 3,5-disubstituted pyrazoles

Article abstract of DOI:10.1016/j.tet.2013.08.047

The reaction of hydroximoyl chlorides with acetylenes in the presence of a copper on iron bimetallic system leads to β-aminoenones via reductive ring opening of isoxazole intermediates. The valuable β-aminoenone building blocks can be isolated or transformed into pyrazoles with the addition of hydrazine in a straightforward one-pot procedure.

Full text of DOI:10.1016/j.tet.2013.08.047

Tetrahedron 69 (2013) 8987e8993
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Copper on iron promoted one-pot synthesis of b-aminoenones and
3,5-disubstituted pyrazoles
*
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ꢀ
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Szabolcs Kovacs, Zoltan Novak
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€
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Eotvos Lorand University, Pazmany Peter stny. 1/a, Budapest 1117, Hungary
a r t i c l e i n f o
a b s t r a c t
Article history:
Received 24 April 2013
Received in revised form 8 August 2013
Accepted 19 August 2013
Available online 24 August 2013
The reaction of hydroximoyl chlorides with acetylenes in the presence of a copper on iron bimetallic
system leads to -aminoenones via reductive ring opening of isoxazole intermediates. The valuable b-
aminoenone building blocks can be isolated or transformed into pyrazoles with the addition of hydrazine
in a straightforward one-pot procedure.
b
Ó 2013 Elsevier Ltd. All rights reserved.
Keywords:
Copper
Enones
Iron
Heterocycles
Reduction
1. Introduction
cleavage is through electron transfer from reducing agents, such as
SmI2,10 Fe(II) complexes11 or iron dichloride.12
The application of multimetallic catalyst systems for metal-
catalyzed reactions provides an attractive strategy for the con-
struction of new chemical bonds. Bimetallic catalyst systems, such
as Pd/Cu are widely used in organic synthesis.1 More recently
several efficient copper/iron-promoted synthetic transformations
were reported, where the cooperation of the metals was beneficial
for the reaction.2
The synthesis of pyrazoles remains of great interest due to their
important role in the agrochemical and pharmaceutical industries.13
Several methods exist for the synthesis of 3,5-disubstituted pyr-
azoles,14 but the most important is the cyclocondensation of hy-
drazine with 1,3-dielectrophilic reagents, such as 1,3-dicarbonyl
compounds,15 ynones,16
ing group at the
-carbon,17 or related compounds.
a,b-unsaturated carbonyls bearing a leav-
b
Copper-catalyzed reactions of hydroximoyl chlorides and ter-
minal acetylenes via in situ nitrile oxide generation are frequently
used methods for the construction of isoxazoles.3 These five-
membered heterocycles can be used in ring transformations to
prepare further heterocyclic systems.4
2. Results and discussion
A copper on iron catalyst was developed in our laboratory for the
efficient thiolation of aromatic halides18 and the azideealkyne cy-
cloaddition.19 We also fully characterized the Cu/Fe system regarding
copper content and structure.19 As a continuation of our work, herein
we report the use of this Cu/Fe bimetallic system in the dipolar cy-
cloaddition of nitrile oxides and alkynes to prepare isoxazoles, which
b
-Aminoenones are versatile synthetic intermediates that are
useful synthons in several applications5 and used in the synthesis
of heterocycles (pyrazoles, pyrroles, pyridinones, pyrimidines).6
Although several methods exist for the synthesis of N-substituted
b
-aminoenones,7 preparation of
b-aminoenones bearing a free
can be transformed into b-aminoenones in a one-pot process via re-
amino group is typically achieved through reductive ring opening
of isoxazoles. The most frequently used methods for isoxazole re-
ductive ring opening are hydrogenation using Raney nickel, palla-
dium on charcoal or platinum catalysts,4,8 or using molybdenum (0)
or iron (0) carbonyl complexes.9 Another way to perform the NeO
ductive NeO bond cleavage using the iron as the electron source.
We began by examining the reaction of N-hydroxy-benzene-
carboximidoyl chloride and phenylacetylene in the presence of
K2CO3 in DMF at 100 ꢀC, but we found only the formation of
diphenylisoxazole (Table 1, entry 1). In the absence of base, the iso-
xazole ring was opened to form b-aminoenone and products 3 and 4
were formed in a 74:5 ratio (Table 1, entry 2). Copper itself was not
able to catalyze the cleavage of NeO bond (entry 3). Increasing the
amount of iron from 10 mol % up to 110%, we obtained better
* Corresponding author. Tel.: þ36 1 372 2100, þ36 1 372 1610; fax: þ36 1 372
ꢀ
2592; e-mail address: novakz@elte.hu (Z. Novak).
0040-4020/$ e see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tet.2013.08.047

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S. Kovacs, Z. Novak / Tetrahedron 69 (2013) 8987e8993
8988
aminoenone ratios (entries 4e6), showing that a stoichiometric
amount of iron is necessary to perform the reductive ring opening.
to assist the opening of the isoxazole ring (entry 2). Based upon
Truscello’s results,12 we tried FeCl2 and FeCl3 as promoters of the
ring opening step, but the formation of
occur in the presence of either additive (entries 3 and 4).
b-aminoenone did not
Table 1
Effect of transition metals on the cycloaddition and the reductive ring openinga
Table 3
Study of the ring opening of isoxazolesa
Entry Metal
Catalyst (mol %) Conversionb
%
Product ratioc 3:4
1d
2
3
5 wt % Cu/Fe
5
5
5
10
50
110
5
86
79
71
79
79
82
80
46
0:86
74:5
2:69
Entry
Reagent
Additive
Conversion (%)b
5 wt % Cu/Fe
Cu powder
Fe powder
Fe powder
Fe powder
CuþFe powder
d
After 1 h
After 3 h
4
5
2:77
1
d
d
0
0
0
0
30
0
0
0
0
0
65
0
25:54
56:26
67:13
0:46
2
5% (5 wt %) Cu/Fe
1.1 equiv FeCl2
1.1 equiv FeCl3
5% (5 wt %) Cu/Fe
d
d
6e
7f
8
3c
d
4c
d
5d
6e
7e
8c,e
9c,e,f
concd HCl (aq)
d
a
HCl
HCl
HCl
HCl
Reaction conditions: 0.25 mmol N-hydroxy-benzenecarboximidoyl chloride,
0.25 mmol phenylacetylene, 0.1 mL DMF, 100 ꢀC, 1 h.
5% (5 wt %) Cu/Fe
1.1 equiv FeCl2
1.1 equiv FeCl2
90
0
100
0
b
Based on phenylacetylene.
Product ratio and conversion were determined with GCeMS.
Reaction with 0.25 mmol K2CO3.
Reaction with the same Fe content as 5 mol % (5 wt %) Cu/Fe.
c
0
0
d
a
Reaction conditions: 0.25 mmol 3,5-diphenylisoxazole, 0.1 mL DMF, 100 ꢀC.
Conversions were determined by GCeMS.
Reaction with the same Fe content as 5 mol % (5 wt %)Cu/Fe.
Reaction with 1 equiv HCl.
Reaction in DMF bubbled with HCl gas.
Reaction carried out in H2 atmosphere.
e
b
c
d
e
f
f
Reaction with the same Cu and Fe content as 5 mol % (5 wt %) Cu/Fe.
Next, we examined the synergistic effect of copper and iron in
the Cu/Fe bimetallic system compared with the separate addition of
copper and iron powder (entry 7). On the basis of three parallel
reactions, we found similar conversions, but the reductive ring
opening was faster in the presence of Cu/Fe (74:5 vs 67:13; entries 2
and 7). In the absence of any transition metal additive, the cyclo-
addition took place in 46% conversion after 1 h (entry 8), but the
conversion reached only 498% after 20 h.
Although, DMF proved to be good solvent for the ring opening
step, we examined the reaction in other media (Table 2). In water,
toluene, and DMSO (entries 1e3.) the reaction gave 82, 48, and 65%
conversion, respectively. However, only the cycloaddition took place
and no aminoenone formation was observed. In n-butanol and ace-
tonitrile (entries 4 and 5) the reductive ringopeningoccurred, but the
conversions were found to be low relative to other solvents. DMF and
DMA give similar conversions (entries 6 and 7), but interestingly in
DMF the aminoenone derivative was the major product.
In our model reaction, HCl was formed from hydroximoyl
chloride during the formation of nitrile oxide. We supposed that
the acid plays crucial role in the ring opening step, therefore we
added concentrated HCl aqueous solution to the reaction and the
conversion of isoxazole to aminoenone was found to be 30% after
1 h and 65% after 3 h (entry 5). However, we observed earlier that
water suppressed the ring opening (Table 2, entry 1). To exclude
water from the reaction mixture, we repeated the reaction using
HCl gas dissolved in DMF. We observed almost complete reaction
after 1 h with copper on iron catalyst (entry 7). Utilization of FeCl2
for the reductive cleavage in DMF(HCl) in the presence and absence
of hydrogen gas did not gave the desired aminoenone product. On
the basis of these studies we can conclude that the transformation
requires the presence of iron metal and HCl.
On the basis of these findings and literature reports, we propose
that the first step of the reaction sequence is the copper-catalyzed
1,3-dipolar cycloaddition between the acetylene (2) and the in situ
generated nitrile oxide.
Table 2
Influence of solvents on the cycloaddition and the ring openinga
In the absence of base, the formed HCl byproduct along with the
iron promote the reductive ring opening of the isoxazole to the b-
aminoenone (3) via electron transfer. The aminoenone product
then can be transformed into heterocyclic molecules, such as di-
substituted pyrazoles (5). To demonstrate the applicability of cop-
per on iron under the developed conditions, we synthesized several
Entry
Solvent
Conversionb
%
Product ratioc 3:4
1
2
3
4
H2O
82
48
65
34
16
75
79
0:82
0:48
0:65
10:24
14:2
26:49
74:5
b-aminoenones from structurally diverse hydroximoyl chlorides
Toluene
DMSO
nBuOH
MeCN
DMA
and terminal acetylenes (Table 4).
5
6
Table 4
7d
DMF
Cu/Fe promoted synthesis of aminoenonesa
a
Reaction conditions: 0.25 mmol N-hydroxy-benzenecarboximidoyl chloride
0.25 mmol phenylacetylene, 0.1 mL DMF, 100 ꢀC, 1 h.
b
Based on phenylacetylene.
Product ratio and conversion were determined with GCeMS.
After 1 h.
c
d
Product
Yieldb (%)
Product
Yieldb (%)
To determine the factors responsible for the opening of the
isoxazole ring, we heated 3,5-diphenylisoxazole in DMF at 100 ꢀC
under a variety of conditions (Table 3). In the absence of any
metal additive, the ring opening does not occur under the re-
action conditions (entry 1). Also, copper on iron itself is not able
71
68
3a
3f

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S. Kovacs, Z. Novak / Tetrahedron 69 (2013) 8987e8993
8989
Table 4 (continued )
sequence, the addition of hydrazine hydrate to the formed amino-
enone should provide 3,5-disubstituted pyrazoles in a one-pot
process.
Product
Yieldb (%)
Product
Yieldb (%)
To demonstrate this transformation, phenylacetylene and N-
hydroxy-benzenecarboximidoyl chloride were reacted in DMF at
50
51
100 ꢀC to provide
b-aminoenone (3a), then hydrazine hydrate was
3g
added into the reaction mixture. To our delight, we observed the
formation of the desired 3,5-diphenylpyrazole (5a) product in
a ring closure step after 2 h reaction time, and the compound was
isolated with 70% yield (Table 5). Using this successfully developed
reaction sequence, we prepared several 3,5-disubstituted pyrazoles
using different hydroximoyl chlorides and acetylenes (Table 5).
Methyl-, methoxy, and halogen substituents on the phenyl ring of
hydroximoyl chloride did not affect the outcome of the reaction
significantly and products (5bee) were isolated with 56e74% yield.
3b
3c
60
70
44
36
3h
3d
3i
Table 5
Sequential one-pot synthesis of pyrazolesa
57
3e
a
Reaction conditions: 1 mmol hydroximoyl chloride, 1 mmol acetylene, 0.4 mL
DMF, 5 mol % (5 wt %)Cu/Fe.
b
Yields of isolated product after chromatographic purification.
Product
Yieldb (%)
70
Product
Yieldb (%)
69
The reaction of phenylacetylene and N-hydroxy-benzenecarbox-
imidoyl chloride in DMF at 100 ꢀC gave the appropriate
b-amino-
enone (3a) in 71% yield. Substrates bearing electron donating methyl
(1b) or methoxy groups (1c) on the phenyl ring of hydroximoyl
chloride gave the corresponding aminoenones 3b and 3c with 50%
and 60% yields, respectively. Reaction of chloro-substituted hydrox-
imoyl chloride (1d) with phenylacetylene under the optimized re-
action conditions afforded the desired product 3d in 70% yield. Using
hydroximoyl chlorides with thiophenyl (1e) and naphthyl (1f) rings,
we obtained the aminoenones (3e, 3f) also with the similar efficiency
(57% and 68%). Reactions were also performed with alkyl acetylenes
bearing bulky tert-butyl and n-hexyl groups, and aminoenones 3g
and 3h were isolated after the ring opening of the alkyl isoxazoles
with 51% and 44% yield. The reaction of N-hydroxy-benzenecarbox-
imidoyl chloride with trimethylsilylacetylene afforded the TMS
substituted aminoenone 3i in lower yield (36%). Unfortunately, ali-
phatic hydroximoyl chlorides and internal acetylenes did not provide
the desired products under the applied conditions.
While the copper-iron bimetallic system enables the cycloaddi-
tion and the subsequent reductive ring opening step under simpler
conditions compared to other metal-promoted procedures, some
part of the metal additive is sacrificed during the transformation.
We performed the synthesis of 3a in larger scale, starting from
5 g (32 mmol) of phenylhydroximoyl chloride, and we obtained the
product in 62% yield. In this reaction, 2.06 g Cu/Fe was used, while
only 602 mg was recovered after the workup. This mass balance is
consistent with consumption of some of the iron additive during
the reductive NeO bond cleavage.
5a
5b
5i
5j
70, 69c
46
65
74
50
47
5c
5k
5l
5d
56
44
55
5e
5m
59d
5f
5n
58
56
70
5g
5o
5h
To exploit the reactivity of
b-aminoenones, we aimed to prepare
nitrogen heterocycles in a one-pot reactionwithout the isolation of
aminoenones (Scheme 1). After conducting the previously developed
Cu/Fe promoted cycloaddition-reductive ring opening reaction
b
-
a
Reaction conditions: 1 mmol hydroximoyl chloride, 1 mmol acetylene, 0.4 mL
DMF, 5 mol % (5 wt %) Cu/Fe 100 ꢀC, 3 h, then added 5 mmol hydrazine hydrate,
100 ꢀC, 2 h.
b
Yields of isolated product after chromatographic purification.
Reaction of N-hydroxy-benzenecarboximidoyl chloride and 3-ethynyltoluene.
Reaction of N-hydroxy-4-nitrobenzenecarboximidoyl chloride and phenyla
c
d
cetylene.
3,5-Disubstituted pyrazole 5b was prepared with the same ef-
ficiency either from the reaction of 3-methyl-N-hydroxy-benze-
necarboximidoyl chloride with phenylacetylene or the reaction of
N-hydroxy-benzenecarboximidoyl chloride and 3-ethynyltoluene
(70% and 69% isolated yield, respectively).
The appropriate pyrazole formation (5f) from a nitro-substituted
substrate could be also achieved, but reduction of the nitro group to
Scheme 1. Proposed reaction steps involving Cu/Fe bimetallic additive.

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S. Kovacs, Z. Novak / Tetrahedron 69 (2013) 8987e8993
8990
the amine was observed under the reductive reaction conditions.
Naphthyl, thiophenyl, and pyridyl hydroximoyl chlorides all provide
the appropriate pyrazoles (5gei) with good yields (58%, 56%, 69%,
respectively). Beyond phenylacetylene, heteroaromatic, and aliphatic
acetylenes as well as trimethylsilylacetylene were also reacted with
hydroximoyl chlorides and, followed by the subsequent treatment
with hydrazine hydrate, we isolated the appropriate pyrazoles 5jem.
The yields of these products varied in the range of 44e50%. Reactions
with methylhydrazine and phenylhydrazine gave 1,2,5-trisubstituted
pyrazoles 5n and 5o with good yields (55% and 70%).
a solution of CuSO4 (126 mg, 0.79 mmol) in H2O (50 mL) was added
dropwise under argon atmosphere over 1 h, and the stirring was
continued for 3 h. The catalyst was separated with a magnet and
washed with deoxygenated H2O (5ꢁ20 mL) then acetone
(3ꢁ20 mL) and dried under reduced pressure.
4.3. General synthesis of aminoenones
A mixture of terminal acetylene (1 mmol, 1 equiv), hydroximoyl
chloride (1 mmol, 1 equiv), 5 mol % (5 w/w%) Cu/Fe (64 mg,
0.05 mmol Cu), and DMF (400 m
L) were heated for 3 h at 100 ꢀC, then
3. Conclusions
the mixture was diluted with ethyl acetate (5 mL). The catalyst was
separated with a magnet and washed with ethyl acetate (4ꢁ5 mL)
and DCM (2ꢁ5 mL). The organic phase was evaporated on Celite and
purified by chromatography on silica gel to give the desired product.
In conclusion, we have developed a simple one-pot procedure
for the preparation of b-aminoenones from hydroximoyl chlorides
and acetylenes through the reductive ring opening of isoxazole
intermediates with the aid of bimetallic copper on iron promoter.
The developed procedure employs mild and convenient conditions
4.4. Synthesis of pyrazoles
compared to existing procedures for the preparation of
enones containing a free NH2 group. Further treatment of
noenones with hydrazine hydrate gave 3,5-disubstituted pyrazoles
in a three step, one-pot sequence.
b
-amino-
A mixture of terminal acetylene (1 mmol, 1 equiv), hydroximoyl
chloride (1 mmol, 1 equiv), 5 mol % (5 w/w%) Cu/Fe (64 mg,
b
-ami-
0.05 mmol Cu), and DMF (400 m
L) were heated for 3e4.5 h at 100 ꢀC,
then the hydrazine monohydrate was added and the mixture was
heated for 2e6 h at 100 ꢀC. After the appropriate time, the reaction
mixture was diluted with ethyl acetate (5 mL), the catalyst was
separated with a magnet and washed with ethyl acetate (4ꢁ5 mL)
and DCM (2ꢁ5 mL). The organic phase was evaporated on Celite and
purified by chromatography on silica gel to give desired pyrazole.
4. Experimental section
4.1. General
Unless otherwise indicated, all starting materials were obtained
from commercial suppliers, and were used without further purifi-
cation. Analytical thin-layer chromatography (TLC) was performed
4.5. Synthesis and characterization
on Merck DC precoated TLC plates with 0.25 mm Kieselgel 60 F254
.
4.5.1. 3-Amino-1,3-diphenylprop-2-en-1-one20 (3a). General pro-
cedure was followed, yellow oil, 157 mg (0.71 mmol, 71% yield),
Rf¼0.33 (hexaneeethyl acetate, 4:1), 1H NMR (250 MHz, CDCl3):
Visualizationwas performed with a 254 nm UV lamp. The 1H and 13
C
NMR spectra were recorded on a Bruker Avance-250 spectrometer
in CDCl3 and DMSO-d6. Chemical shifts are expressed in parts per
d 10.43 (br s,1H), 7.97e7.93 (m, 2H), 7.66e7.62 (m, 2H), 7.48e7.43 (m,
million (
d
) using residual solvent protons as internal standards (
d
6H), 6.15 (s, 1H), 5.53 (br s, 1H), 13C NMR (62.5 MHz, CDCl3):
d 190.1,
7.26 for 1H,
d
77.0 for 13C). Coupling constants (J) are reported in
162.9, 140.3, 137.6, 131.0, 130.6, 129.0, 128.3, 127.2, 126.3, 91.8, MS (EI,
Hertz (Hz). Splitting patterns are designated as s (singlet), d (dou-
blet), t (triplet), m (multiplet). Combination gas chromatography
and low resolution mass spectrometry was obtained on an Agilent
70 eV): m/z (%): 222 (100, [Mþ]), 146 (72), 103 (31), 91 (19), 77 (37).
4.5.2. 3-Amino-3-(3-methylphenyl)-1-phenylprop-2-en-1-one
(3b). General procedure was followed, yellow oil, 119 mg
(0.50 mmol, 50% yield), Rf¼0.29 (hexaneeethyl acetate, 4:1), 1H
6890N Gas Chromatograph (30 mꢁ0.25 mm column with 0.25
mm
HP-5MS coating, He carrier gas) and Agilent 5973 Mass Spectrom-
eter (Ion source: EIþ, 70 eV, 230 ꢀC; interface: 300 ꢀC). IR spectra
were obtained on a Bruker IFS55 spectrometer on a single-reflection
NMR (250 MHz, CDCl3):
d 10.43 (br s, 1H), 7.97e7.94 (m, 2H),
7.48e7.33 (m, 7H), 6.14 (s, 1H), 5.51 (br s, 1H), 2.43 (s, 3H), 13C NMR
(62.5 MHz, CDCl3): 190.1, 163.1, 140.4, 138.8, 137.6, 131.4, 130.9,
€
diamond ATR unit. All melting points were measured on Buchi 501
d
apparatus and are uncorrected. High-resolution mass spectra were
acquired on an Agilent 6230 time-of-flight mass spectrometer
equipped with a Jet Stream electrospray ion source in positive ion
128.9, 128.2, 127.2, 126.9, 123.4, 91.7, 21.4, MS (EI, 70 eV): m/z (%):
236 (100, [Mþ]), 160 (77), 117 (55), 91 (20), 77 (69), IR (ATR) 3340,
1519, 1478, 1306, 1230, 747 cmꢃ1, HRMS calcd for C16H16NO [MþH]þ
238.1226 found 238.1230.
mode. Injections of 0.1e0.3
ml were directed to the mass spec-
trometer at a flow rate 0.5 ml/min (70% acetonitrileewater mixture,
0.1% formic acid), using an Agilent 1260 Infinity HPLC system. Jet
Stream parameters: drying gas (N2) flow and temperature: 10.0 l/
min and 325 ꢀC, respectively; nebulizer gas (N2) pressure: 10 psi;
capillary voltage: 4000 V; sheath gas flow and temperature: 325 ꢀC
and 7.5 l/min; TOFMS parameters: fragmentor voltage: 120 V;
skimmer potential: 120 V; OCT 1 RF Vpp:750 V. Full-scan mass
spectra were acquired over the m/z range 100e2500 at an acquisi-
tion rate of 250 ms/spectrum and processed by Agilent MassHunter
B.03.01 software. Iron source for Cu/Fe preparation: SigmaeAldrich
4.5.3. 3-Amino-3-(2-methoxylphenyl)-1-phenylprop-2-en-1-one
(3c). General procedure was followed, yellow solid, 152 mg
(0.60 mmol, 60% yield), mp: 92e94 ꢀC, Rf¼0.11 (hexaneeethyl ac-
etate, 4:1), 1H NMR (250 MHz, CDCl3):
d 10.71 (br s, 1H), 7.94e7.91
(m, 2H), 7.57 (dd, 1H, J1¼7.58 Hz, J2¼1.74 Hz), 7.46e7.39 (m, 4H),
7.02 (dd, 2H, J1¼13.90 Hz, J2¼7.58 Hz), 6.25 (br s, 1H), 6.05 (s, 1H),
3.89 (s, 3H), 13C NMR (62.5 MHz, CDCl3):
d 189.8, 162.0, 156.7, 140.7,
131.5, 130.7, 129.6, 128.1, 127.1, 125.2, 121.1, 111.8, 92.6, 55.8, MS (EI,
70 eV): m/z (%): 252 (7, [Mþ]), 222 (100), 176 (13), 134 (31), 105 (36),
77 (39), IR (ATR) 1594, 1520, 1241, 1037, 755, 732, 645 cmꢃ1, HRMS
calcd for C16H16NO2 [MþH]þ 254.1176 found 254.1183.
Product number: 44,890, Iron puriss ꢂ99.5% 6e9
mm. DMF Sigma-
eAldrich puriss ꢂ99.5% was used for the reactions.
4.2. Preparation of copper on iron catalyst
4.5.4. 3-Amino-3-(4-chlorophenyl)-1-phenylprop-2-en-1-one
(3d). General procedure was followed, white solid, 181 mg
(0.71 mmol, 70% yield), mp: 92e93 ꢀC, Rf¼0.32 (hexaneeethyl ac-
A round-bottom flask was charged with iron powder (5.00 g,
89.5 mmol) and H2O (deoxygenated with argon) (50 mL). The
mixture was stirred vigorously with a mechanical stirrer and
etate, 4:1), 1H NMR (250 MHz, CDCl3):
d 10.37 (br s, 1H), 7.95e7.91
(m, 2H), 7.57 (d, 2H, J¼8.5 Hz), 7.48e7.41 (m, 5H), 6.10 (s, 1H), 5.49

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S. Kovacs, Z. Novak / Tetrahedron 69 (2013) 8987e8993
8991
(br s, 1H), 13C NMR (62.5 MHz, CDCl3):
d
190.2, 161.5, 140.1, 136.7,
yield), (b) 161 mg (0.69 mmol, 69% yield), mp: 127e131 ꢀC, lit.:
145e147 ꢀC, Rf¼0.28 (hexaneeethyl acetate, 4:1), 1H NMR
136.0, 131.2, 129.2, 128.3, 127.7, 127.2, 92.0, MS (EI, 70 eV): m/z (%):
256 (100, [Mþ]), 180 (44), 137 (23), 117 (22), 89 (14), 77 (32), IR
(ATR) 1593, 1527, 1476, 1223, 845, 749, 618 cmꢃ1, HRMS calcd for
(250 MHz, CDCl3):
d
7.74e7.70 (m, 2H), 7.50 (d, 2H, J¼7.74 Hz),
7.37e7.20 (m, 4H), 7.11 (d, 1H, J¼7.90 Hz), 6.80 (s, 1H), 2.30 (s, 3H),
C
15H13ClNO [MþH]þ 258.0680 found 258.0684.
13C NMR (62.5 MHz, CDCl3):
d
138.4, 131.4, 131.0, 128.83, 128.81,
128.7, 128.6, 128.0, 126.3, 125.6, 122.7, 99.9, 21.3, MS (EI, 70 eV): m/z
4.5.5. 3-Amino-1-phenyl-3-(thiophen-2-yl)-prop-2-en-1-one
(3e). General procedure was followed, brown solid, 130 mg
(0.57 mmol, 57% yield), mp: 77e79 ꢀC, Rf¼0.31 (hexaneeethyl ace-
(%): 234 (100, [Mþ]), 205 (10), 117 (10), 77 (9).
4.5.12. 3-(4-Methoxyphenyl)-5-phenyl-1H-pyrazole (5c).24 General
procedure was followed (3þ2 h), pale yellow solid, 163 mg
(0.65 mmol, 65% yield), mp: 154e157 ꢀC, lit.: 160 ꢀC, Rf¼0.63
tate, 4:1), 1H NMR (250 MHz, CDCl3):
d 7.96e7.92 (m, 2H), 7.51e7.44
(m, 5H), 7.14e7.11 (m, 1H), 6.27 (s, 1H), 13C NMR (62.5 MHz, CDCl3):
d
190.1,155.1,140.1,139.9,131.1,128.3,128.1,127.2,126.5, 91.3, MS (EI,
(hexaneeethyl acetate, 1:1), 1H NMR (250 MHz, CDCl3):
d 7.70e7.66
70 eV): m/z (%): 228 (100, [Mþ]),152 (82),109 (41), 97 (17), 77 (37), IR
(m, 2H), 7.62e7.57 (m, 2H), 7.36e7.26 (m, 3H), 6.86e6.80 (m, 2H),
(ATR) 3157, 1612, 1592, 1533, 1504, 1223, 716 cmꢃ1, HRMS calcd for
C
6.69 (s, 1H), 3.79 (s, 3H), 13C NMR (62.5 MHz, CDCl3):
d
159.5, 131.5,
13H11NNaOS [MþNa]þ 252.0454 found 252.0457.
128.7, 127.9, 126.9, 125.5, 123.8, 114.1, 99.3, 55.2, MS (EI, 70 eV): m/z
(%): 250 (100, [Mþ]), 235 (39), 207 (21), 178 (23), 125 (9), 77 (12).
4.5.6. 3-Amino-3-(1-naphthyl)-1-phenylprop-2-en-1-one
(3f). General procedure was followed, yellow oil,186 mg (0.68 mmol,
68% yield), Rf¼0.33 (hexaneeethyl acetate, 4:1), 1H NMR (250 MHz,
4.5.13. 3-(2-Methoxyphenyl)-5-phenyl-1H-pyrazole (5d). General
procedure was followed (3þ2 h), yellow oil,186 mg (0.74 mmol, 74%
yield), Rf¼0.67 (hexaneeethyl acetate, 1:1), 1H NMR (250 MHz,
CDCl3):
d 10.53 (br s, 1H), 8.28e8.24 (m, 1H), 7.94e7.88 (m, 4H),
7.60e7.37 (m, 7H), 6.07 (s, 1H), 5.68 (br s, 1H), 13C NMR (62.5 MHz,
CDCl3): 190.0, 162.8, 140.0, 135.9, 133.6, 131.1, 130.20, 129.9, 128.4,
CDCl3):
d
7.95e7.92 (m, 2H), 7.75 (dd, 1H, J1¼7.63 Hz, J2¼1.59 Hz),
d
7.48e7.42 (m, 2H), 7.38e7.28 (m, 2H), 7.09e7.02 (m, 2H), 6.98 (s,1H),
128.2, 127.2, 126.9, 126.4, 125.5, 125.15, 125.10, MS (EI, 70 eV): m/z (%):
3.92 (s, 3H), 13C NMR (62.5 MHz, CDCl3):
d
155.8, 151.1, 142.0, 133.3,
272 (21, [Mþ]), 256 (49), 196 (23), 168 (100), 152 (28), 127 (28), 105
129.2, 128.5, 127.8, 127.6, 125.6, 121.3, 117.6, 111.5, 99.9, 55.6, MS (EI,
(38), 77 (47), IR (ATR) 3326, 1562, 1519, 1391, 1225, 776, 691 cmꢃ1
,
70 eV): m/z (%): 250 (100, [Mþ]),178 (27),146 (33),119 (47),104 (30),
HRMS calcd for C19H16NO [MþH]þ 274.1226 found 274.1229.
89 (26), 77 (30), IR (ATR) 1587, 1454, 1244, 1023, 748, 692 cmꢃ1
,
HRMS calcd for C16H15N2O [MþH]þ 251.1179 found 251.1186.
4.5.7. 1-Amino-4,4-dimethyl-1-phenylpent-1-en-3-one
(3g).21 General procedure was followed, off white solid, 103 mg
(0.51 mmol, 51% yield), mp: 72e74 ꢀC, lit.: 75 ꢀC, Rf¼0.39 (hex-
4.5.14. 3-(4-Chlorophenyl)-5-phenyl-1H-pyrazole
(5e).24 General
procedure was followed (3þ2 h), white solid, 143 mg (0.56 mmol,
aneeethyl acetate, 4:1), 1H NMR (250 MHz, CDCl3):
d 9.98 (br s, 1H),
56% yield), mp: 216e217 ꢀC, lit.: 216e218 ꢀC, Rf¼0.26 (hex-
7.57e7.55 (m, 2H), 7.54e7.42 (m, 3H), 5.63 (s, 1H), 5.19 (br s, 1H),
aneeethyl acetate, 4:1), 1H NMR (250 MHz, DMSO-d6):
d 13.44 (br s,
1.21 (s, 9H), 13C NMR (62.5 MHz, CDCl3):
d
206.5, 161.7, 138.0, 130.3,
1H), 7.84 (s, 4H), 7.48e7.32 (m, 5H), 7.20 (s,1H), 13C NMR (62.5 MHz,
128.9, 126.3, 90.7, 42.3, 27.7, MS (EI, 70 eV): m/z (%): 203 (4, [Mþ]),
DMSO-d6): d 128.7, 126.7, 125.0, 99.8, MS (EI, 70 eV): m/z (%): 235 (8,
146 (100), 117 (6), 103 (16), 91 (11), 77 (7).
[Mþ]), 254 (100), 225 (13), 189 (15), 94 (17).
4.5.8. 1-Amino-1-phenylnon-1-en-3-one (3h). General procedure
was followed, yellow oil, 101 mg (0.44 mmol, 44% yield), Rf¼0.39
4.5.15. 4-(3-Phenyl-1H-pyrazol-5-yl)aniline (5f).25 General pro-
cedure was followed (3þ4 h), orange solid, 139 mg (0.5 mmol, 59%
yield), mp: 162e164 ꢀC, lit.: 163 ꢀC, Rf¼0.30 (hexaneeethyl acetate,
(hexaneeethyl acetate, 4:1), 1H NMR (250 MHz, CDCl3):
d 9.96 (br s,
1H), 7.57e7.54 (m, 2H), 7.46e7.41 (m, 3H), 5.44 (s, 1H), 5.25 (br s,
1H), 2.38 (t, 2H, J¼7.58 Hz), 1.70e1.58 (m, 2H), 1.30 (s, 6H), 0.88 (t,
1:1), 1H NMR (250 MHz, DMSO-d6):
d 12.96 (br s, NH), 7.82 (d,
J¼7.27 Hz, 2H), 7.51e7.39 (m, 4H), 7.29 (t, J¼7.11 Hz, 1H), 6.90 (s, 1H),
3H, J¼6.48 Hz), 13C NMR (62.5 MHz, CDCl3):
d 200.7, 160.8, 137.4,
130.4, 128.9, 126.2, 94.8, 43.0, 31.7, 29.2, 25.9, 22.5, 14.0, MS (EI,
6.63 (d, J¼8.37 Hz, 2H), 5.29 (br s, NH2), 13C NMR (62.5 MHz, DMSO-
d6): d 148.6,128.5,127.3,124.9,113.8, 97.5, MS (EI, 70 eV): m/z (%): 235
70 eV): m/z (%): 231 (9, [Mþ]), 174 (9), 160 (36), 146 (100), 119 (41),
(8, [Mþ]), 206 (24),180 (8),130 (9),116 (100),104 (24), 91 (97), 65 (25).
103 (23), 91 (14), IR (ATR) 2925, 1603, 1524, 1484, 150, 694 cmꢃ1
,
HRMS calcd for C15H21NNaO [MþNa]þ 254.1515 found 254.1521.
4.5.16. 3-(1-Naphthyl)-5-phenyl-1H-pyrazole (5g). General pro-
cedure was followed (3þ6 h), white solid, 157 mg (0.58 mmol, 58%
yield), mp: 134e136 ꢀC, Rf¼0.26 (hexaneeethyl acetate, 4:1), 1H
4.5.9. 3-Amino-3-phenyl-1-(trimethylsilyl)-prop-2-en-1-one
(3i). General procedure was followed, yellow solid, 78 mg (0.36 mmol,
36% yield), mp: 93e96 ꢀC, Rf¼0.23 (hexaneeethyl acetate, 4:1), 1H
NMR (250 MHz, CDCl3):
d 8.31e8.27 (m, 1H), 7.91e7.83 (m, 2H),
7.79e7.75 (m, 2H), 7.58e7.31 (m, 7H), 6.87 (s, 1H), 13C NMR
(62.5 MHz, CDCl3): 149.3, 146.4, 133.8, 131.7, 131.3, 128.97, 128.92,
NMR (250 MHz, CDCl3):
d
10.80 (br s,1H), 7.38e7.34 (m, 2H), 7.28e7.22
d
(m, 3H), 5.72 (s, 1H), 5.19 (br s, 1H), 0.00 (s, 9H), 13C NMR (62.5 MHz,
128.7, 128.3, 128.0, 127.0, 126.6, 126.0, 125.7, 125.4, 125.2, 103.8, MS
CDCl3):
d
227.7, 158.6, 137.1, 130.7, 129.0, 126.4, 100.9, ꢃ2.9, MS (EI,
(EI, 70 eV): m/z (%): 270 (100, [Mþ]), 239 (16), 167 (30), 139 (11), 120
70 eV): m/z(%): 218 (20, [Mþ]), 204(90),146 (100),126 (19),104(40), 91
(30), 73 (70), IR (ATR) 1600,1531,1480,1240, 832, 746, 686 cmꢃ1, HRMS
calcd for C12H18NOSi [MþH]þ 220.1152 found 220.1156.
(12), 104 (15), IR (ATR) 3218, 1559, 1171, 1073, 963, 758, 685 cmꢃ1
,
HRMS calcd for C19H15N2 [MþH]þ 271.1230 found 271.1237.
4.5.17. 5-Phenyl-3-(thiophen-2-yl)-1H-pyrazole
(5h).22 General
4.5.10. 3,5-Diphenyl-1H-pyrazole (5a).22 General procedure was
followed (3þ2 h), pale yellow solid, 154 mg (0.70 mmol, 70% yield),
mp: 196e198 ꢀC, lit.: 200 ꢀC, Rf¼0.28 (hexaneeethyl acetate, 4:1),1H
procedure was followed (3þ2 h), yellow solid, 127 mg (0.56 mmol,
56% yield), mp: 172 ꢀC, Rf¼0.26 (hexaneeethyl acetate, 4:1), 1H
NMR (250 MHz, CDCl3):
d 7.65e7.62 (m, 2H), 7.31e7.19 (m, 5H),
NMR (250 MHz, CDCl3):
d
7.73e7.71 (m, 4H), 7.41e7.32 (m, 6H), 6.83
7.00e6.96 (m, 1H), 6.66 (s, 1H), 13C NMR (62.5 MHz, CDCl3):
d 135.0,
(s,1H), 13C NMR (62.5 MHz, CDCl3):
d
131.3,128.8,128.2,125.6,100.1,
130.8,128.8,128.3,127.5,125.5,124.7,124.1, 99.9, MS (EI, 70 eV): m/z
MS (EI, 70 eV): m/z (%): 220 (100, [Mþ]), 191 (23), 104 (11), 77 (14).
(%): 226 (100, [Mþ]), 197 (31), 165 (10), 152 (10), 77 (10).
4.5.11. 3-m-Tolyl-5-phenyl-1H-pyrazole (5b).23 General procedure
was followed (3þ2 h), yellow solid, (a) 163 mg (0.70 mmol, 70%
4.5.18. 5-Phenyl-3-(3-pyridyl)-1H-pyrazole (5i).26 General pro-
cedure was followed (3þ2 h), off white solid, 104 mg (0.47 mmol,

ꢀ ꢀ
S. Kovacs, Z. Novak / Tetrahedron 69 (2013) 8987e8993
8992
47% yield), mp: 186e188 ꢀC, lit.: 187e188 ꢀC, Rf¼0.16 (hex-
help of Prof. K. Torkos and Dr. Zs. Eke for providing the necessary
analytical measurements is gratefully acknowledged. Thanks to
Prof. Tim Peelen for the proofreading of this manuscript.
aneeethyl acetate, 1:1), 1H NMR (250 MHz, DMSO-d6):
d 9.08 (s,
1H), 8.53 (s, 1H), 8.20 (d, 1H, J¼8.06 Hz), 7.84 (d, 2H, J¼7.42 Hz),
7.50e7.31 (m, 5H), 13C NMR (62.5 MHz, DMSO-d6):
d 146.3, 132.1,
128.8, 125.0, 123.7, 100.0, MS (EI, 70 eV): m/z (%): 221 (100, [Mþ]),
Supplementary data
192 (14), 77 (14), 51 (13).
Experimental procedures, characterization data, and copies of
the 1H NMR and 13C NMR spectra for the products are available.
Supplementary data associated with this article can be found in the
online version, at http://dx.doi.org/10.1016/j.tet.2013.08.047.
4.5.19. 3-(Phenyl)-5-(2-pyridyl)-1H-pyrazole (5j).27 General pro-
cedure was followed (3þ2 h), pale yellow solid, 101 mg (0.46 mmol,
46% yield), mp: 143e144 ꢀC, lit.: 159 ꢀC, Rf¼0.19 (hexaneeethyl
acetate, 1:1), 1H NMR (250 MHz, CDCl3):
d
8.70 (d, 1H, J¼4.90 Hz),
7.90e7.75 (m, 4H), 7.47e7.24 (m, 4H), 7.08 (s, 1H), 13C NMR
References and notes
(62.5 MHz, CDCl3):
d 149.4, 148.7, 137.0, 132.5, 128.7, 128.0, 125.7,
122.9, 120.1, 100.4, MS (EI, 70 eV): m/z (%): 221 (100, [Mþ]), 192 (67),
1. (a) Lee, J. M.; Na, Y.; Han, H.; Chang, S. Chem. Soc. Rev. 2004, 33, 302e312; (b)
Doucet, H.; Hierso, J.-C. Angew. Chem., Int. Ed. 2007, 46, 834e871; (c) Chinchilla,
R.; Najera, C. Chem. Rev. 2007, 107, 874e922.
165 (15), 115 (16).
2. (a) Taillefer, M.; Xia, N.; Ouali, A. Angew. Chem., Int. Ed. 2007, 46, 934e936; (b)
Mao, J.; Xie, G.; Wu, M.; Guo, J.; Ji, S. Adv. Synth. Catal. 2008, 350, 2477e2482; (c)
Rao Volla, C. M.; Vogel, P. Tetrahedron Lett. 2008, 49, 5961e5964; (d) Su, Y.; Jia, W.;
Jiao, N. Synthesis 2011, 11, 1678e1690; (e) Shirakawa, E.; Yamagami, T.; Kimura, T.;
Yamaguchi, S.; Hayashi, T. J. Am. Chem. Soc. 2005, 127, 17164e17165.
4.5.20. 5-Phenyl-3-tert-butyl-1H-pyrazole (5k).24 General pro-
cedure was followed (3þ2 h), white solid, 100 mg (0.50 mmol, 50%
yield), mp: 104e106 ꢀC, Rf¼0.26 (hexaneeethyl acetate, 4:1), 1H
NMR (250 MHz, CDCl3):
d 7.80e7.76 (m, 2H), 7.44e7.32 (m, 3H),
3. (a) Himo, F.; Lovell, T.; Hilgraf, R.; Rostovstev, V. V.; Noodleman, L.; Sharpless, K. B.;
6.42 (s, 1H), 1.40 (s, 9H), 13C NMR (62.5 MHz, CDCl3):
d 132.7, 128.8,
Fokin, V. V. J. Am. Chem. Soc. 2005, 127, 210e216; (b) Hansen, T. V.; Peng, W.; Fokin,
€
V. V. J. Org. Chem. 2005, 70, 7761e7764; (c) Jager, V.; Colinas, P. A. Synthetic
128.6, 128.3, 127.7, 125.5, 98.8, 31.3, 30.3, MS (EI, 70 eV): m/z (%):
Applications of 1,3-Dipolar Cycloaddition Chemistry toward Heterocycles and Natural
Products; Wiley: Hoboken, NJ, 2002; pp. 361e472.
200 (33, [Mþ]), 185 (100), 158 (13), 145 (11), 77 (10).
4. Grunanger, P.; Finzi, P. V. Isoxazoles In The Chemistry of Heterocyclic Compounds;
Weisserberger, A., Taylor, E. C., Eds.; Interscience: New York, NY, 1991.
5. (a) Kucklander, U. Enaminones as Synthones In The Chemistry of Functional
Groups; Rapport, Z., Ed.; John Wiley and Sons: New York, NY, 1994, Chapter 10;
(b) Granik, V.; Makarov, V. Adv. Heterocycl. Chem. 1999, 72, 283; (c) Elassar, A.-Z.
A.; El-Khair, A. A. Tetrahedron 2003, 59, 8463e8480.
4.5.21. 5-Hexyl-3-phenyl-1H-pyrazole (5l).22 General procedure
was followed (3þ2 h), yellow solid, 107 mg (0.47 mmol, 47% yield),
mp: 69e70 ꢀC, Rf¼0.26 (hexaneeethyl acetate, 4:1), 1H NMR
(250 MHz, CDCl3): d 11.0 (br s, 1H), 7.76e7.73 (m, 2H), 7.39e7.29 (m,
6. (a) Lue, P.; Greenhill, J. V. Adv. Heterocycl. Chem.1996, 67, 207e343; (b) Alberola, A.;
3H), 6.35 (s, 1H), 2.59 (t, 2H, J¼8.10 Hz), 1.62e1.59 (m, 2H), 1.26 (m,
ꢀ
Calvo, L. A.; Gonzalez-Ortega, A.; Ruíz, M. C. S.; Yustos, P. J. Org. Chem. 1999, 64,
6H), 0.89 (s, 3H), 13C NMR (62.5 MHz, CDCl3):
d
132.8, 128.6, 127.7,
ꢀ
ꢀ
9493e9498; (c) Calvo, L. A.; Gonzalez-Nogal, A. M.; Gonzalez-Ortega, A.; Ruíz, M. C.
S. Tetrahedron Lett. 2001, 42, 8981e8984; (d) Stanovnik, B.; Svete, J. Chem. Rev. 2004,
104, 2433; (e) Negri, G.; Kascheres, C.; Kascheres, A. J. J. Heterocycl. Chem. 2004, 41,
125.7, 100.9, 31.5, 29.2, 28.9, 26.3, 22.5, 14.0, MS (EI, 70 eV): m/z (%):
228 (18, [Mþ]), 171 (42), 158 (100), 128 (17).
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461; (f) Calle, M.; Calvo, L. A.; Gonzalez-Ortega, A.; Gonzalez-Nogal, A. M.
Tetrahedron 2006, 62, 611e618.
4.5.22. 3-Phenyl-5-trimethylsilyl-1H-pyrazole (5m).28 General pro-
cedure was followed (8 h), white solid, 95 mg (0.44 mmol, 44%
yield), mp: 123 ꢀC, Rf¼0.35 (hexaneeethyl acetate, 4:1), 1H NMR
7. (a) Samantaray, M. K.; Dash, C.; Shaikh, M. M.; Pang, K.; Butcher, R. J.; Ghosh, P.
Inorg. Chem. 2011, 50, 1840e1848; (b) Xu, X.; Du, P.; Cheng, D.; Wang, H.; Li, X.
Chem. Commun. 2012, 1811e1813; (c) Zhang, M.; Abdukader, A.; Fu, Y.; Zhu, C.
Molecules 2012, 17, 2812e2822.
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Sugowdz, G. J. Chem. Soc. 1954, 665e668; (c) Casnati, G.; Quilico, A.; Ricca, A.;
Vita Finzi, P. Tetrahedron Lett. 1966, 7, 233e238; (d) McGregor, D. N.; Corbin, U.;
Swigor, J. E.; Cheney, L. C. Tetrahedron 1969, 25, 389e395; (e) Baraldi, P. G.;
Barco, A.; Benetti, S.; Manfredini, S.; Pollini, G. P.; Simoni, D. Tetrahedron Lett.
1984, 25, 4313e4316; (f) Kenar, J. A. J. Am. Oil Chem. Soc. 2003, 80, 1027e1032;
(g) Singh, V.; Saxena, R.; Batra, S. J. Org. Chem. 2005, 70, 353e356.
9. (a) Nitta, M.; Kobayashi, T. Tetrahedron Lett. 1982, 23, 3925e3928; (b) Nitta, M.;
Kobayashi, T. J. Chem. Soc., Perkin Trans. 1 1985, 7, 1401e1406.
(250 MHz, CDCl3): d 7.78e7.74 (m, 2H), 7.35e7.28 (m, 2H), 7.25e7.18
(m, 1H), 6.65 (s, 1H), 0.24 (s, 9H), 13C NMR (62.5 MHz, CDCl3):
d
151.9, 144.3, 133.3, 128.6, 127.6, 125.9, 109.8, ꢃ1.24, MS (EI, 70 eV):
m/z (%): 216 (69, [Mþ]), 201 (100), 185 (14), 100 (16).
4.5.23. 1-Methyl-3,5-diphenyl-1H-pyrazole (5n).29 General pro-
cedure was followed (8 h), white solid, 115 mg (0.55 mmol, 55%
yield), mp: 58e59 ꢀC, lit.: 54e57 ꢀC, Rf¼0.53 (hexaneeethyl acetate,
10. Natale, N. R. Tetrahedron Lett. 1982, 23, 5009e5012.
4:1), 1H NMR (250 MHz, CDCl3):
d
7.87e7.84 (m, 2H), 7.48e7.32 (m,
150.5,
11. Kijima, M.; Nambu, Y.; Endo, T. J. Org. Chem. 1985, 50, 1140e1142.
12. Auricchio, S.; Bini, A.; Pastormerlo, E.; Truscello, A. M. Tetrahedron 1997, 53,
10911e10920.
8H), 6.63 (s, 1H), 3.94 (s, 3H), 13C NMR (62.5 MHz, CDCl3):
d
13. Elguero, J. Compr. Heterocycl. Chem. II 1996, 3, 1e75.
14. For reviews, see: (a) Kost, A. N.; Grandberg, I. I. Adv. Heterocycl. Chem. 1966, 6,
145.0, 133.4, 130.6, 128.7, 128.67, 128.6, 128.5, 127.6, 125.5, 103.2,
37.7, MS (EI, 70 eV): m/z (%): 234 (100, [Mþ]), 189 (8), 130 (10), 118
(10), 103 (11), 77 (18).
347e429; (b) Elguero, J. Compr. Heterocycl. Chem. 1984, 5, 167e303; (c) Fustero,
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S.; Sanchez-Rosello, M.; Barrio, P.; Simon-Fuentes, A. Chem. Rev. 2011, 111,
6984e7034; (d) Janin, Y. L. Chem. Rev. 2012, 112, 3924e3958; (e) Gribble, G.;
Joule, J. Progress in Heterocyclic Chemistry; Elsevier, 2011; Vol. 23, Chapter 5.4;
(f) Yoon, J.-Y.; Lee, S-gi; Shin, H. Curr. Org. Chem. 2011, 15, 657e674; (g) Joule, J.
In Comprehensive Heterocyclic Chemistry; Katritzky, A. R., Ramsden, C. A.,
Scriven, E. F. V., Taylor, R. J. K., Eds.; Elsevier: Amsterdam, The Netherlands,
2008; Vol. 4, pp 1e142.
4.5.24. 1,3,5-Triphenyl-1H-pyrazole (5o).22 General procedure was
followed (8 h), white solid, 115 mg (0.70 mmol, 70% yield), mp:
136e137 ꢀC, lit.: 140e142 ꢀC, Rf¼0.75 (hexaneeethyl acetate, 4:1),
1H NMR (250 MHz, CDCl3):
d
8.02 (d, 2H, J¼7.4 Hz), 7.48e7.42 (m,
15. (a) Heller, S. T.; Natarajan, S. R. Org. Lett. 2006, 8, 2675e2678; (b) Wang, Z.-X.; Qin,
H.-L. Green Chem. 2004, 6, 90e92; (c) Polshettiwar, V.; Varma, R. S. Tetrahedron
Lett. 2008, 49, 397e400; (d) Guillou, S.; Bonhomme, F. J.; Janin, Y. L. Synthesis
2008, 3504e3508; (e) Barge, M.; Kamble, S.; Kumbhar, A.; Rashinkar, G.;
Salunkhe, R. Monatsch. Chem. 2013, 144, 1213e1218.
5H), 7.37e7.31 (m, 8H), 6.87 (s, 1H), 13C NMR (62.5 MHz, CDCl3):
151.9, 144.4, 140.1, 133.0, 130.6, 128.9, 128.7, 128.6, 128.4, 128.3,
d
128.0, 127.4, 125.8, 125.3, 105.2, MS (EI, 70 eV): m/z (%): 296 (100,
[Mþ]), 192 (11), 165 (17), 77 (36).
16. (a) Engelmann, A.; Kirmse, W. Chem. Ber. 1973, 106, 3092e3094; (b) Bishop, B. C.;
Brands, K. M. J.; Gibb, A. D.; Kennedy, D. J. Synthesis 2004, 43e52; (c) Grotjahn, D. B.;
Van, S.; Combs, D.; Lev, D. A.; Schneider, C.; Rideout, M.; Meyer, C.; Hernandez, G.;
Mejorado, L. J. J. Org. Chem. 2002, 67, 9200e9209; (d) Zora, M.; Kivrak, A. J. Org.
Acknowledgements
€
Chem. 2011, 76, 9379e9390; (e) Willy, B.; Muller, T. J. J. Org. Lett. 2011, 13,
€
This project was supported by the ‘Lendulet’ Research Scholar-
2082e2085; (f) Kirkham, J. D.; Edeson, S. J.; Stokes, S.; Harrity, J. P. A. Org. Lett. 2012,
ꢀ
14, 5354e5357.
ship of the Hungarian Academy of Sciences and by the Janos Bolyai
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