Synthesis of pyrazoles via CuI-mediated electrophilic cyclizations of α,β-alkynic hydrazones

Article abstract of DOI:10.1021/jo201685p

Synthesis of pyrazoles via electrophilic cyclization of α,β-alkynic hydrazones by copper(I) iodide is described. When treated with copper(I) iodide in the presence of triethylamine in refluxing acetonitrile, α,β-alkynic hydrazones, prepared readily from hydrazines and propargyl aldehydes and ketones, undergo electrophilic cyclization to afford pyrazole derivatives in good to excellent yields. The reaction appears to be general for a variety of α,β-alkynic hydrazones and tolerates the presence of aliphatic, aromatic, and ferrocenyl moieties with electron-withdrawing and electron-donating substituents.

Full text of DOI:10.1021/jo201685p

Article
pubs.acs.org/joc
Synthesis of Pyrazoles via CuI-Mediated Electrophilic Cyclizations of
α,β-Alkynic Hydrazones
Metin Zora* and Arif Kivrak
Department of Chemistry, Middle East Technical University, 06531 Ankara, Turkey
S
* Supporting Information
ABSTRACT: Synthesis of pyrazoles via electrophilic cycliza-
tion of α,β-alkynic hydrazones by copper(I) iodide is
described. When treated with copper(I) iodide in the presence
of triethylamine in refluxing acetonitrile, α,β-alkynic hydra-
zones, prepared readily from hydrazines and propargyl
aldehydes and ketones, undergo electrophilic cyclization to
afford pyrazole derivatives in good to excellent yields. The
reaction appears to be general for a variety of α,β-alkynic
hydrazones and tolerates the presence of aliphatic, aromatic,
and ferrocenyl moieties with electron-withdrawing and electron-donating substituents.
reactions furnished 1-alkyl/aryl-5-ferrocenylpyrazoles (3, 1,5-
isomer) and/or 1-alkyl/aryl-3-ferrocenylpyrazoles (4, 1,3-
isomer), the former being the single or the major product of
the reaction in most cases. Interestingly, if hydrazines are
employed instead of hydrazinium salts, pyrazoles are obtained
in very low yields. When hydrazinium salts, however, are used,
the reaction medium becomes somewhat acidic, and pyrazoles
are formed in good yields. Obviously, acid catalysis favors the
reaction, but in this case, the proportion of 1,3-pyrazole isomer
4 increases at the expense of 1,5-pyrazole isomer 3, consistent
with the observations of other researchers using analogous
systems.27 As previously proposed, these reactions go through
the corresponding acetylenic hydrazone and/or conjugated
addition intermediates, depending upon the reaction conditions
and/or the identity of the substituent in hydrazine derivatives
2.28 We anticipated that electrophilic cyclization of such
acetylenic hydrazones, which can be easily prepared from
hydrazines and acetylenic aldehydes and ketones, would
provide a rapid entry to a wide variety of pyrazole derivatives.
Recently, an explosive increase of interest in electrophilic
cyclizations of functionally substituted alkynes has happened,29
thus becoming an enormously active and inventive field of
heterocyclic synthesis because they often take place in a
regioselective manner as well as in very mild reaction
conditions.30 By employing such electrophilic cyclizations, a
large variety of important heterocycles and carbocycles have
been synthesized, including furans,31 benzofurans,32 thio-
phenes,33 benzothiophenes,34 bicyclic β-lactams,35 chro-
mones,36 cyclic carbonates,37 isoxazoles,38 indoles,39 isocou-
marins,40 isochromenes,41 isoindolinones,42 naphthalenes,43
and quinolines.44 In this regard, we have recently reported
the synthesis of α,β-alkynic hydrazones 7 and their electrophilic
INTRODUCTION
■
Pyrazoles are popular targets for synthetic chemists primarily
because of their diverse and potent biological properties.1 In
fact, pyrazoles have been extensively studied in the last few
decades as a prominent class of heterocycles2 and still receive
great attention for both pharmaceutical and agricultural
benefits. Pyrazoles have been reported to exhibit a wide
range of biological properties, including analgesic,3 antibacte-
rial,4 antidepressant,5 anti-inflammatory,6,7 antimicrobial,8
antiobesity,9 antiviral,10 appetite suppressant,11 cholesterol-
lowering,12 antihyperglycemic,13 antihypertensive,14 and anti-
cancer15 activities. In addition, they are present as the core
structure in a large variety of leading drugs and pesticides, such
as Celebrex,7 Viagra16 and Zometapine,17 and Cyenopyrafen,18
Fenpyroximate,19 and Tebufenpyrad.20 Typical methods for the
synthesis of pyrazoles involve the approaches based either on
the condensation of hydrazines with 1,3-dicarbonyl com-
pounds21 and their 1,3-dielectrophilic equivalents including
α,β-unsaturated aldehydes and ketones22 or on the intermo-
lecular 1,3-dipolar cycloaddition of diazoalkanes and nitrili-
mines with alkenes and alkynes.23 Some drawbacks of these
protocols, such as the poor reactivity and regioselectivity and
the potential hazardousness and detonation of the substrates,
limit their practical application to some extent. Notably,
pyrazoles are rarely prepared by the functionalization of
unsubstituted or less substituted pyrazoles because they often
require a laborious multistep synthesis.24 Consequently, there
still exists a great demand to develop new methodologies for
the synthesis of substituted pyrazole derivatives. Although over
the years, diverse methodologies have been developed,25 the
regiocontrolled and broadly applicable synthesis of pyrazoles
remains a noteworthy challenge for synthetic chemists.
We have recently investigated the reactions of 3-ferrocenyl-
propynal (1) with hydrazinium salts (2) (Scheme 1).26
Depending upon the substitution pattern of hydrazines, these
Received: August 11, 2011
Published: October 12, 2011
© 2011 American Chemical Society
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Scheme 1
cyclization into 4-iodopyrazole derivatives 8 in good to
excellent yields by using molecular iodine in the presence of
sodium bicarbonate (Scheme 2).45 Iodocyclizations have been
our knowledge, copper-mediated electrophilic cyclizations of
α,β-alkynic hydrazones have not been explored, which in fact
could provide a rapid entry to the generation of pyrazole
libraries. As part of a program to synthesize new pyrazole
derivatives as potential pharmaceuticals, we have further
explored the electrophilic cyclizations of such alkynic
hydrazones. We have disclosed that upon treatment with
copper(I) iodide in the presence of triethylamine in refluxing
acetonitrile, α,β-alkynic hydrazones, prepared readily from
hydrazines and acetylenic aldehydes and ketones, undergo
electrophilic cyclization to afford pyrazole derivatives in good
to excellent yields.53 We herein report the results of this study.
Scheme 2
found to be general for a wide range of α,β-alkynic hydrazones
and tolerated the presence of aliphatic, aromatic, heteroar-
omatic, and ferrocenyl moieties with electron-withdrawing and
electron-donating substituents.
RESULTS AND DISCUSSION
■
The required α,β-acetylenic aldehydes and ketones can be
easily prepared according to standard literature procedures as
shown in Scheme 3. The lithiation of terminal alkynes 9a−d
with n-BuLi, followed by the formylation of in situ generated
lithium acetylides with DMF, affords α,β-acetylenic aldehydes
5a−d in good to excellent yields.54 It is noteworthy to mention
that these high yielding formylation reactions have required a
reverse quench into a phosphate buffer as the key. 3-
Ferrocenylpropynal (1) can be synthesized from ethynylferro-
cene by a similar formylation reaction.55 On the other hand, the
reaction of in situ generated lithium acetylide with ZnCl2 yields
zinc acetylide, the coupling of which with acetyl chloride leads
to acetylenic methyl ketone 5e (Scheme 3).56 Acetylenic
phenyl ketone 5f can be prepared directly from the terminal
alkyne and benzoyl chloride by a palladium-catalyzed coupling
reaction.57
Subsequently, we synthesized a variety of α,β-acetylenic
hydrazones 7 from alkynals and alkynones 5. In fact, we
prepared 27 kinds of hydrazone derivatives, 8 of which (Z-7e−
g, Z-7j, Z-7n−p, and Z-7v) were synthesized for the first time
(Scheme 4 and Table 1). Note that we reported the synthesis
of the remaining 19 hydrazone derivatives (Z-7a−d, Z-7h−i, Z-
7k−m, Z-7q−u, and Z-7w−aa) in a recent study,45 which were
prepared in refluxing dioxane at 100 °C or in the absence of
solvent at 80 °C (see Tables 2 and 3 for the structures of these
hydrazones). In light of the previous study, condensation
reactions for the synthesis of new hydrazones were conducted
Amazingly, electrophilic cyclizations of such acetylenic
hydrazones were not utilized amply for the synthesis of
pyrazoles since a literature search on this subject exposed very
few reports. Gonzales-Nogal reported the synthesis of 5-
silylpyrazoles by electrophilic cyclization of β-silyl-substituted
acetylenic hydrazones with ethyl chloroformate and aluminum
chloride, and molecular iodine.46 Although the Larock research
group planned to study electrophilic cyclization of acetylenic
N,N-dimethylhydrazones to furnish 4-halopyrazoles, they were
unable to prepare the required hydrazones.47 Thus, they
develop another method to 4-halopyrazoles, but it does not
incorporate electrophilic cyclization. The Wada research group
synthesized pyrazoles and dihydropyrazoles by a reagent-
controlled iodocyclization of propargylic hydrazides.48 Lately,
Liu and Xu and co-workers developed a method for the
synthesis of fluorinated pyrazoles via gold(I)-catalyzed electro-
philic cyclization of acetylenic hydrazones in the presence of
Selectfluor.49
Recently, copper-mediated (both stoichiometric and cata-
lytic) reactions have attracted great attention because the ability
of these compounds to promote a wide range of reactions has
allowed for their broad application.50,51 In particular, electro-
philic cyclization of functionally substituted alkynes by copper
Lewis acids has been recognized as an attractive way to produce
a variety of important heterocycles.52 However, to the best of
Scheme 3
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obtained as minor products. Notably, E isomers E-7 were not
so stable in the reaction conditions, on silica gel during flash
chromatography and/or on standing at room temperature in a
solvent, that they partially converted into Z isomers Z-7. For
this reason, we kept the reaction time longer and minimized the
formation of E isomers to some level since they changed into Z
isomers. As indicated by theoretical calculations at the density
functional theory (DFT) level,45 Z isomers of acetylenic
hydrazones are thermodynamically more stable than their E
isomers. As a result, the isolation of E isomers E-7 was not
attempted, and the electrophilic cyclizations were carried out
with Z isomers Z-7.
Scheme 4
in the neat conditions (without solvent) at 80 °C (Scheme 4).
As illustrated in Table 1, the yields of hydrazones changed from
47 to 93%. As noted in both this study and earlier work,45 from
the reactions of 3-alkyl- or aryl-substituted propargyl aldehydes
and ketones 5, Z isomers of acetylenic hydrazones, Z-7, were
resulted as major products, whereas E isomers, E-7, were
As mentioned previously, E and Z isomers of acetylenic
hydrazones can easily be identified on the basis of their 13C
Table 1. Synthesis of Acetylenic Hydrazones
a
Isolated yield.
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CH3CN, pyrazole 10a was obtained in 60% yield, but the
reaction took approximately 8 h (Table 2, entry 2). On the
other hand, the reaction of hydrazone Z-7a with 1 equiv of CuI
in the presence of 1 equiv of NEt3 in CH3CN at 82 °C for 1.5 h
provided pyrazole 10a in 64% yield (Table 2, entry 4). When
the same reaction was carried out for 2 h, pyrazole 10a was
obtained in 73% yield (Table 2, entry 5). Notably, electrophilic
cyclization was quite fast in the presence of NEt3 in refluxing
CH3CN and went to completion in nearly 2 h. On the other
hand, in refluxing CH2Cl2, no reaction occurred (Table 2, entry
7). The reaction conducted with 0.05 equiv of CuI in refluxing
CH3CN was relatively slow and afforded pyrazole 10a in 20%
yield in 2 h, along with the recovered hydrazone Z-7a (72%)
(Table 2, entry 9). However, the same reaction carried out for
23 h went to completion and provided 10a in 61% yield (Table
2, entry 10). The reaction performed with 0.10 equiv of CuI
afforded 10a in 62% yield in 15 h (Table 2, entry 11).
Interestingly, the use of 2 equiv of NEt3 in the reaction did not
improve the yield (62%), but it shortened the reaction time
considerably (6.5 h) (Table 2, entry 12). When the reaction
was carried out with 0.15 equiv of CuI, pyrazole 10a was
obtained in 72% yield (Table 2, entry 13), very close to that
(73%) obtained with the stoichiometric amount of CuI (Table
2, entry 5). Electrophilic cyclization of Z-7a was also tested at
relatively higher temperatures, such as in dioxane at 100 °C and
toluene at 110 °C. The reactions conducted with 0.05 and 0.10
equiv of CuI in refluxing dioxane yielded pyrazole 10a in 55
and 69% yields, respectively (Table 2, entries 14 and 15). When
the latter reaction was carried out in refluxing toluene, 10a was
formed in 66% yield (Table 2, entry 16). Higher temperatures
did not increase the yield of 10a significantly. Notably, the
catalytic usage of CuI has increased the reaction time as
compared to its stoichiometric amount. Hence, the electrophilic
cyclizations were performed with 1 equiv of CuI in the presence
of 1 equiv of NEt3 in refluxing CH3CN. The results from a
systematic study are given in Table 3.
As depicted in Table 3, a variety of α,β-alkynic hydrazone
derivatives Z-7a−aa were employed in these pyrazole-forming
electrophilic cyclizations. 1,5-Dialkyl/aryl-substituted pyrazoles
10a−p were obtained in 57−96% yields (Table 3, entries 1−
16), whereas 1,3,5-trialkyl/aryl-substituted pyrazoles 10q−w
were isolated in 54−99% yields (Table 3, entries 17−23). On
the other hand, 5-ferrocenyl-1-aryl-substituted pyrazoles 10x−
aa were resulted in 44−86% yields (Table 3, entries 24−27). It
is worth mentioning that ferrocenyl-substituted pyrazoles have
potential for biological and medicinal studies because,
according to recent studies, the incorporation of a ferrocenyl
group into such structures may enhance their current biological
activities or bring new medicinal properties.26,28,61 In general,
CuI-mediated electrophilic cyclizations proceed well and
yielded pyrazole derivatives in good to excellent yields. In
addition, these cyclizations were found to be general for a wide
range of α,β-alkynic hydrazones and tolerated the presence of
aliphatic, aromatic, and ferrocenyl moieties with electron-
withdrawing and electron-donating substituents.
Table 2. Electrophilic Cyclization of Acetylenic Hydrazone
Z-7a
CuI (amt
(equiv))
NEt3(amt
(equiv))
temp.
(°C)
time
(h)
%
yield
a
entry
solvent
1
2
3
4
5
6
7
8
1
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH2Cl2
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
CH3CN
dioxane
dioxane
toluene
rt
82
rt
2
8
1
60
1
1
1
1
1
1
1
1
1
1
2
1
1
1
1
2
1
82
82
82
40
rt
1.5
2
64
73
66
1
2
2
1
2
0.05
0.05
0.05
0.10
0.10
0.15
0.05
0.10
2
b
9
82
82
82
82
82
100
100
110
2
20
61
62
62
72
55
69
66
10
11
12
13
14
15
16
23
15
6.5
12
10
9
0.10
9
a
b
Isolated yield. Starting hydrazone Z-7a was recovered in 72% yield.
NMR spectra.45,58 Two alkynic carbons in the E isomer
resonate closely, and the chemical shift difference between
these carbons is about 3−12 ppm. On the other hand, in the Z
isomer, the alkynic carbon adjacent to the carbonyl group is
comparatively upfield while the other alkynic carbon is
relatively downfield, and the chemical shift difference between
these carbons is roughly 22−30 ppm. In brief, the absolute
value of chemical shift difference between alkynic carbons in
the Z isomer is typically bigger as compared to that in the E
isomer.
After synthesizing the requisite hydrazones 7, we investigated
their electrophilic cyclizations to pyrazoles. Initially, electro-
philic cyclization of phenylpropynal phenylhydrazone (Z-7a),
prepared from 3-phenyl-2-propynal (5a) and phenylhydrazine
(6a), was examined under several conditions to find optimal
reaction conditions (Table 2). It is well-known that copper salts
have mild Lewis acidity and have been commonly used as
catalysts in organic synthesis.51 Among these salts, we preferred
CuI, one of the most employed reagents for inducing
transformations, because it takes advantage of its affinity to
carbon−carbon unsaturated bonds rather than oxygen func-
tional groups. In addition, CuI was used effectively in the
electrophilic cyclization of functionally substituted alkynes.59 In
the light of literature studies, we chose NEt3 as a base and
CH3CN as a reaction solvent because they are one of the most
commonly used bases and solvents in such transformations.60
As a result, we carried out the optimization reactions with CuI/
NEt3 system in CH3CN. When the hydrazone Z-7a was reacted
with 1 equiv of CuI in CH3CN for 2 h at room temperature, no
conversion to pyrazole 10a was observed, as indicated by TLC
(Table 2, entry 1). In fact, all reactions conducted at room
temperature failed to afford pyrazole 10a (Table 2, entries 3
and 8). When the same reaction was performed in refluxing
A possible mechanism for the formation of pyrazoles 10 is
given in Scheme 5. The activation of the alkyne moiety of
hydrazone Z-7 by CuI is followed by the nucleophilic addition
of the secondary nitrogen atom to form protonated pyrazole
12. Then, hydrogen atom transfer into copper gives
intermediate 13. Finally, reductive elimination yields pyrazole
derivative 10.
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Table 3. Synthesis of Pyrazoles via CuI-Mediated Electrophilic Cyclization
a
Isolated yield.
Scheme 5
CONCLUSION
■
In summary, we have developed a simple and efficient copper-
mediated electrophilic cyclization for the synthesis of pyrazoles.
We have first prepared α,β-alkynic hydrazone derivatives by the
condensation reactions of hydrazines with acetylenic aldehydes
and ketones in neat condition at 80 °C, and then investigated
their electrophilic cyclizations with copper(I) iodide. When
reacted with copper(I) iodide in the presence of triethylamine
in refluxing acetonitrile, α,β-alkynic hydrazones smoothly
underwent electrophilic cyclization to furnish pyrazole
derivatives in good to excellent yields. The reaction has been
found to be general for a wide range of α,β-alkynic hydrazones
and allowed the presence of aliphatic, aromatic, and ferrocenyl
groups with electron-withdrawing and electron-donating
moieties. It is anticipated that the efficiency and operational
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C), 120.8 (C), 116.4 (d, J = 22.5 Hz, CH), 115.5 (CH), 114.4 (CH),
111.8 (d, J = 25.2 Hz, CH), 101.8 (C), 78.6(C); IR (neat) 3313, 3053,
2183, 1604, 1533, 1504, 1488, 1440, 1344, 1257, 1207, 1101, 1047,
858, 802, 746, 682 cm−1; MS (ESI, m/z) 295.04 [M + Na]+, 273.06
[M + H]+; HRMS (ESI) calcd. for C15H10ClFN2Na 295.0413 [M +
Na]+, found 295.0409; calcd. for C15H11ClFN2 273.0595 [M + H]+,
found 273.0589.
simplicity of the method could make it potentially attractive for
library construction of pyrazoles, particularly in the area of
pharmaceuticals.
EXPERIMENTAL SECTION
■
General information. 1H and 13C NMR spectra were recorded at
400 and 100 MHz, respectively. Chemical shifts are reported in parts
per million (ppm) downfield from an internal TMS (trimethylsilane)
reference. Coupling constants (J) are reported in hertz (Hz), and spin
multiplicities are presented by the following symbols: s (singlet), br s
(broad singlet), d (doublet), t (triplet), q (quartet), p (pentet), and m
(multiplet). DEPT 13C NMR information is given in parentheses as C,
CH, CH2, and CH3. Infrared spectra (IR) were recorded by using
attenuated total reflection (ATR). Band positions are reported in
reciprocal centimeters (cm−1). Band intensities are indicated relative to
the most intense band and are listed as br (broad), vs (very strong), s
(strong), m (medium), w (weak), and vw (very weak). Mass spectra
(MS) were obtained by using electrospray ionization (ESI) with
Micro-Tof; m/z values are reported (for each measurement, the mass
scale was recalibrated with sodium formiate clusters, and samples were
dissolved and measured in MeOH). High resolution mass spectra
(HRMS) were also obtained by using electrospray ionization (ESI)
with Micro-Tof. Flash chromatography was performed using thick-
walled glass columns and “flash grade” silica (230−400 mesh). Thin
layer chromatography (TLC) was performed by using commercially
prepared 0.25 mm silica gel plates, and visualization was effected with
short wavelength UV lamp (254 nm). The relative proportions of
solvents in chromatography solvent mixtures refer to the volume/
volume ratio. All commercially available reagents were used directly
without purification unless otherwise stated. All the solvents used in
reactions were distilled for purity. The inert atmosphere was created
by slight positive pressure (ca. 0.1 psi) of argon. All glassware was
dried in an oven prior to use. 3-Ferrocenylpropynal (1),54,55 3-phenyl-
2-propynal (phenylpropiolaldehyde or phenylpropargyl aldehyde)
(5a),54,62 3-(p-tolyl)propiolaldehyde (5b),54,62 3-(4-methoxyphenyl)-
propiolaldehyde (5c),54,63 oct-2-ynal (5d),54,64 4-phenylbut-3-yn-2-
one (5e),56 and 1,3-diphenylprop-2-yn-1-one (5f)57 were prepared
according to standard literature protocols. α,β-Alkynic hydrazones Z-
7a−d, Z-7h−i, Z-7k−m, Z-7q−u, and Z-7w−aa were synthesized
according to recent literature procedures.45
(Z)-1-(2,5-Difluorophenyl)-2-(3-phenylprop-2-yn-1-ylidene)-
hydrazine (Z-7g). 3-Phenyl-2-propynal (200 mg, 1.55 mmol) and
(2,5-difluorophenyl)hydrazine (223.3 mg, 1.55 mmol) were employed
1
to afford 186.5 mg (47%) of the indicated product: H NMR (400
MHz, CDCl3) δ 8.85 (br s, 1H, NH), 7.52 (m, 2H), 7.40 (m, 3H),
7.20 (m, 1H), 6.97 (m, 1H), 6.72 (s, 1H), 6.49 (m, 1H); 13C NMR
(100 MHz, CDCl3) δ 159.8 (d, J = 240 Hz, C), 145.9 (d, J = 232 Hz,
C), 133.1 (t, J = 11.5 Hz, C), 131.9 (CH), 129.8 (CH), 128.6 (CH),
121.2 (CH), 118.0 (CH), 115.5 (dd, J = 20.4 and 10.4 Hz, CH), 106.0
(dd, J = 24.5 and 6.9 Hz, CH), 103.0 (C), 102.0 (d, J = 28 Hz, CH),
79.0 (C); IR (neat) 3334, 3078, 2185, 1633, 1541, 1519, 1461, 1440,
1350, 1247, 1155, 1120, 975, 839, 796, 773, 748, 715, 680 cm−1; MS
(ESI, m/z) 279.07 [M + Na]+, 257.09 [M + H]4; HRMS (ESI) calcd.
for C15H10F2N2Na 279.0709 [M + Na]+, found 279.0704; calcd. for
C15H11F2N2 257.0891 [M + H]+, found 257.0885.
(Z)-1-(2,5-Difluorophenyl)-2-(3-(p-tolyl)prop-2-yn-1-
ylidene)hydrazine (Z-7j). 3-p-Tolylpropiolaldehyde (200 mg, 1.38
mmol) and (2,5-difluorophenyl)hydrazine (198.7 mg, 1.38 mmol)
were employed to afford 298.2 mg (80%) of the indicated product: 1H
NMR (400 MHz, CDCl3) δ 8.87 (br s, 1H), 7.41 (d, J = 7.9 Hz, 2H),
7.19 (m, 1H), 7.18 (d, J = 7.7 Hz, 2H), 6.96 (m, 1H), 6.71 (s, 1H),
6.47 (m, 1H), 2.37 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.8 (d,
J = 239.5 Hz, C), 145.9 (d, J = 234.5 Hz, C), 140.3 (C), 133.2 (t, J =
10.8 Hz, C), 131.8 (CH), 129.5 (CH), 118.3 (CH), 118.1 (C), 115.5
(dd, J = 9.7 Hz, 20.2 Hz, CH), 105.9 (dd, J = 6.9, J = 24.8 Hz, CH),
103.0 (C), 102.0 (dd, J = 28.8, J = 2.5 Hz, CH), 78.6 (C), 21.6 (CH3);
IR (neat) 3330, 3078, 2920, 2181, 1631, 1542, 1515, 1456, 1342, 1247,
1153, 1116, 1078, 844, 813, 794, 756 cm−1; MS (ESI, m/z) 293.09 [M
+ Na]+; HRMS (ESI) calcd. for C16H12F2N2Na 293.0866 [M + Na]+,
found 293.0861.
(Z)-1-(Oct-2-yn-1-ylidene)-2-(4-(trifluoromethyl)phenyl)-
hydrazine (Z-7n). Oct-2-ynal (200 mg, 1.61 mmol) and (4-
(trifluoromethyl)phenyl)hydrazine (283.8 mg, 1.61 mmol) were
employed to afford 317.9 mg (70%) of the indicated product: 1H
NMR (400 MHz, CDCl3) δ 8.64 (br s, 1H, NH), 7.49 (d, J = 8.5 Hz,
2H), 7.09 (d, J = 8.4 Hz, 2H), 6.45 (s, 1H), 2.49 (td, J = 7.1 and 1.4
Hz, 2H), 1.63 (p, J = 7.4 Hz, 2H), 1.42 (m, 4H), 0.93 (t, J = 7.1 Hz,
3H); 13C NMR (100 MHz, CDCl3) δ 146.3 (C), 126.6 (m, CH),
124.6 (d, J = 269.5 Hz, C), 122.3 (q, J = 32.5 Hz, C), 117.9 (CH),
112.6 (CH), 105.0 (C), 71.5 (C), 31.1 (CH2), 28.0 (CH2), 22.2
(CH2), 19.6 (CH2), 13.3 (CH3); IR (neat) 3315, 2958, 2933, 2861,
2198, 1614, 1527, 1481, 1317, 1263, 1157, 1109, 1060, 833 cm−1; MS
(ESI, m/z) 283.14 [M + H]+; HRMS (ESI) calcd. for C15H18F3N2
283.1422 [M + H]+, found 283,1417.
(Z)-1-(3-Chloro-4-fluorophenyl)-2-(oct-2-yn-1-ylidene)-
hydrazine (Z-7o). Oct-2-ynal (200 mg, 1.61 mmol) and (3-chloro-4-
fluorophenyl)hydrazine (294.6 mg, 1.61 mmol) were employed to
afford 398.4 mg (93%) of the indicated product: 1H NMR (400 MHz,
CDCl3) δ 8.23 (br s, 1H, NH), 6.94 (m, 1H), 6.82 (t, J = 8.7 Hz, 1H),
6.66 (m, 1H), 6.20 (s, 1H), 2.25 (td, J = 7.1 and 1.0 Hz, 2H), 1.44 (p, J
= 7.4 Hz, 2H), 1.21 (m, 4H), 0.75 (t, J = 6.9 Hz, 3H); 13C NMR (100
MHz, CDCl3) δ 152.8 (J = 239.5 Hz, C), 140.72 (C), 121.5 (d, J =
18.3 Hz, C), 117.0 (CH), 116.8 (J = 22.8 Hz, CH), 114.7 (CH), 112.2
(J = 6.8 Hz, CH), 104.8 (C), 71.5 (C), 31.1 (CH2), 28.1 (CH2), 22.2
(CH2), 19.7 (CH2), 13.9 (CH3); IR (neat) 3315, 2956, 2931, 2860,
2198, 1610, 1502, 1340, 1253, 1207, 1091, 844, 804, 731 cm−1; MS
(ESI, m/z) 267.11 [M + H]+; HRMS (ESI) calcd. for C14H17ClFN2
267.1065 [M + H]+, found 267.1059.
General Procedure for the Synthesis of α,β-Alkynic
Hydrazones (Z-7). A mixture of arylhydrazine (2 mmol) and
propargyl aldehyde or ketone (2 mmol) in a round-bottom flask
was heated at 80 °C under argon for 5 h. After the reaction was over,
the residue was purified by flash column chromatography on silica gel
using hexane/ethyl acetate (9:1) as the eluent to afford the desired
product.
(Z)-1-(3-Phenylprop-2-yn-1-ylidene)-2-(4-(trifluoromethyl)-
phenyl)hydrazine (Z-7e). 3-Phenyl-2-propynal (136 mg, 1.05
mmol) and (4-(trifluoromethyl)phenyl)hydrazine (184.1 mg, 1.05
mmol) were employed to afford 178.5 mg (59%) of the indicated
1
product: H NMR (400 MHz, CDCl3) δ 8.76 (br s, 1H, NH), 7.53
(m, 4H), 7.41 (m, 3H), 7.15 (d, J = 8.44 Hz, 2H), 6.69 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 146.0 (C), 131.8 (CH), 129.8 (CH),
128.7 (CH), 126.7 (m, CH), 124.6 (d, J = 269 Hz, C), 122.8 (q, J = 30
Hz, C), 121.2 (C), 116.9 (CH), 112.9 (CH), 102.5 (C), 79.0 (C); IR
(neat) 3323, 3070, 3039, 2185, 1614, 1541, 1523, 1488, 1326, 1259,
1159, 1093, 1058, 819, 754, 686 cm−1; MS (ESI, m/z) 311.08 [M +
Na]+, 289.10 [M + H]+; HRMS (ESI) calcd. for C16H11F3N2Na
311.0771 [M + Na]+, found 311.0767; calcd. for C16H12F3N2 289.0953
[M + H]+, found 289.0947.
(Z)-1-(3-Chloro-4-fluorophenyl)-2-(3-phenylprop-2-yn-1-
ylidene)hydrazine (Z-7f). 3-Phenyl-2-propynal (185 mg, 1.42
mmol) and (3-chloro-4-fluorophenyl)hydrazine (228 mg, 1.42
mmol) were employed to afford 309 mg (80%) of the indicated
(Z)-1-(2,5-Difluorophenyl)-2-(oct-2-yn-1-ylidene)hydrazine
(Z-7p). Oct-2-ynal (200 mg, 1.61 mmol) and (2,5-difluorophenyl)-
hydrazine (231.8 mg, 1.61 mmol) were employed to afford 354.4 mg
1
product: H NMR (400 MHz, CDCl3) δ 8.53 (br s, 1H, NH), 7.50
(m, 2H), 7.39 (m, 3H), 7.17 (m, 1H), 7.03 (m, 1H), 6.94 (m, 1H),
6.62 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 152.5 (d, J = 18 Hz, C),
139.9 (C), 131.3 (CH), 129.2 (CH), 128.2 (CH), 121.1 (d, J = 18 Hz,
1
(88%) of the indicated product: H NMR (400 MHz, CDCl3) δ 8.67
(br s, 1H), 7.16 (m, 1H), 6.85 (m, 1H), 6. 48 (s, 1H), 6.43 (m, 1H),
9384
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2.48 (t, J = 6.87 Hz, 2H), 1.62 (p, 2H), 1.43 (m, 2H), 1.36 (m, 2H),
0.92 (t, J = 7.16 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 159.7 (d, J
= 203.6 Hz, C), 145.7 (d, J = 235.9 Hz, C), 133.4 (t, J = 11 Hz, C),
118.9 (CH), 115.4 (dd, J = 20.3, 10.4 Hz, CH), 105.5 (dd, J = 24.5, 7.4
Hz, CH), 105.4 (C), 101.9 (d, J = 31.5 Hz, CH), 71.4 (C), 31.0
(CH2), 28.0 (CH2), 22.2 (CH2), 19.6 (CH2), 13.8 (CH3); IR (neat)
3328, 2958, 2931, 2862, 2198, 1631, 1542, 1517, 1456, 1338, 1288,
1244, 1157, 1107, 1066, 852, 790 cm−1; MS (ESI, m/z) 273.12 [M +
Na]+, 251.14 [M + H]+; HRMS (ESI) calcd. for C14H16F2N2Na
273.1178 [M + Na]+, found 273.1174; calcd. for C14H17F2N2 251.1360
[M + H]+, found 251.1354.
product: 1H NMR (400 MHz, CDCl3) δ 7.65 (d, J = 1.4 Hz, 1H), 7.40
(m, 5H), 6.19 (s, 1H), 2.62 (t, J = 7.6 Hz, 2H), 1.57 (p, J = 7.3 Hz,
2H), 1.26 (m, 4H), 0.83 (t, 3H); 13C NMR (100 MHz, CDCl3) δ
143.8 (C), 140.1 (C), 139.8 (CH), 129.0 (CH), 127.8 (CH), 125.4
(CH), 105.3 (CH), 31.4 (CH2), 28.5 (CH2), 26.2 (CH2), 22.3 (CH2),
13.3 (CH3); IR (neat) 2954, 2929, 286, 1598, 1537, 1500, 1454, 1394,
1201, 1070, 1012, 923, 761, 694 cm−1; MS (ESI, m/z) 237.14 [M +
Na]+, 215.15 [M + H]+; HRMS (ESI) calcd. for C14H18N2Na
237.1367 [M + Na]+, found 237.1362; calcd. for C14H19N2 215.1549
[M + H]+, found 215.1543.
5-Phenyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole (10e).
Hydrazone Z-7e (45 mg, 0.16 mmol), CuI (30.4 mg, 0.16 mmol),
and NEt3 (16.6 mg, 0.16 mmol) were employed to afford 38.2 mg
(Z)-1-(3-Chloro-4-fluorophenyl)-2-(1,3-diphenylprop-2-yn-1-
ylidene)hydrazine (Z-7v). 1,3-Diphenyl-2-propyn-1-one (diphenyl-
propynone) (200 mg, 0.97 mmol) and (3-chloro-4-fluorophenyl)-
hydrazine (155 mg, 0.97 mmol) were employed to afford 219.5 mg
1
(83%) of the indicated product: H NMR (400 MHz, CDCl3) δ 7.67
(s, 1H), 7.50 (d, J = 8.4 Hz, 2H), 7.34 (d, J = 8.4 Hz, 2H), 7.27 (m,
3H), 7.16 (m, 2H), 6.44 (s, 1H); 13C NMR (100 MHz, CDCl3) δ
143.3 (C), 142.8 (C), 141.1 (CH), 130.3 (C), 129.1 (q, J = 32.8 Hz,
C), 128.9 (CH), 128.7 (CH), 128.6 (CH), 126.0 (CH), 124.8 (CH),
123.8 (d, J = 270.5 Hz, C), 108.9 (CH); IR (neat) 3085, 3064, 1618,
1521, 1452, 1421, 1379, 1321, 1164, 1101, 1060, 1014, 956, 920, 846,
827, 794, 758 cm−1; MS (ESI, m/z) 311.08 [M + Na]+, 289.10 [M +
H]+; HRMS (ESI) calcd. for C16H11F3N2Na 311.0771 [M + Na]+,
found 311.0767; calcd. for C16H12F3N2 289.0953 [M + H]+, found
289.0947.
1
(65%) of the indicated product: H NMR (400 MHz, CDCl3) δ 8.62
(br s, 1H), 7.98 (d, J = 7.6 Hz, 2H), 7.64 (m, 2H), 7.46 (m, 5H), 7.37
(d, J = 6.9 Hz, 1H), 7.31 (m, 1H), 7.09 (t, J = 8.7 Hz, 1H), 7.04 (m,
1H); 13C NMR (100 MHz, CDCl3) δ 153.0 (d, J = 240.5 Hz, C),
140.5 (C), 135.5 (C), 131.9 (CH), 129.8 (CH), 128.8 (CH), 128.6
(CH), 128.4 (CH), 126.9 (CH), 125.6 (CH), 121.6 (d, J = 18.5 Hz,
C), 121.3 (C), 116.9 (d, J = 22.3 Hz, CH), 115.0 (CH), 112.6 (d, J =
6.2 Hz, CH), 104.1 (C), 78.6 (C); IR (neat) 3305, 3053, 3024, 2185,
1606, 1506, 1488, 1442, 1207, 1157, 835, 812, 752, 680 cm−1; MS
(ESI, m/z) 371.07 [M + Na]+; HRMS (ESI) calcd. for
C21H14ClFN2Na 371.0727 [M + Na]+, found 371.0722.
1-(3-Chloro-4-fluorophenyl)-5-phenyl-1H-pyrazole (10f).
Hydrazone Z-7f (100 mg, 0.37 mmol), CuI (70.3 mg, 0.37 mmol),
and NEt3 (37.4 mg, 0.37 mmol) were employed to afford 72.4 mg
General Procedure for the Synthesis of Pyrazoles (10). To a
stirred solution of α,β-alkynic hydrazone Z-7 (0.25 mmol) in CH3CN
(7 mL) under argon was added CuI (0.25 mmol) and Et3N (0.25
mmol), and the resulting solution was allowed to stir under reflux at 82
°C for 2 h. After the reaction was over, the solvent was evaporated, and
the residue was purified by flash chromatography on silica gel using
hexane/ethyl acetate (9:1) as the eluent to afford the desired product.
1,5-Diphenyl-1H-pyrazole (10a). Hydrazone Z-7a (55 mg, 0.25
mmol), CuI (47.5 mg, 0.25 mmol), and NEt3 (25 mg, 0.25 mmol)
1
(72%) of the indicated product: H NMR (400 MHz, CDCl3) δ 7.73
(d, J = 1.6 Hz, 1H), 7.50 (dd, J = 6.3, J = 2.1 Hz, 1H), 7.37 (m, 3H),
7.26 (m, 2H), 7.09 (m, 2H), 6.52 (d, J = 1.6 Hz, 1H); 13C NMR (100
MHz, CDCl3) δ 157.1 (d, J = 248 Hz, C), 143.2 (C), 140.7 (CH),
136.7 (C), 130.0 (C), 128.8 (CH), 128.7 (CH), 128.6 (CH), 127.4
(CH), 124.7 (d, J = 7.5 Hz, CH), 123.4 (d, J = 18.6 Hz, C), 116.5 (d, J
= 22.2 Hz, CH), 108.3 (CH); IR (neat) 2989, 2869, 2360, 1502, 1415,
1261, 1218, 1134, 1074, 925, 879, 823, 786, 756, 702 cm−1; MS (ESI,
m/z) 295.04 [M + Na]+, 273.06 [M + H]+; HRMS (ESI) calcd. for
C15H10ClFN2Na 295.0413 [M + Na]+, found 295.0409; calcd. for
C15H11ClFN2 273.0595 [M + H]+, found 273.0589.
1
were employed to afford 42.4 mg (77%) of the indicated product: H
NMR (400 MHz, CDCl3) δ 7.75 (s, J = 1.6 Hz, 1H), 7.32 (m, 8H),
7.27 (m, 2H), 6.53 (d, J = 1.6 Hz, 1H); 13C NMR (100 MHz, CDCl3)
δ 143.0, 140.3, 140.2, 130.6, 128.9, 128.8, 128.4, 128.2, 127.4, 125.2,
107.8. The spectral data were in agreement with those reported
previously for this compound.65
1-(2,5-Difluorophenyl)-5-phenyl-1H-pyrazole (10g). Hydra-
zone Z-7g (51.2 mg, 0.2 mmol), CuI (38 mg, 0.2 mmol), and NEt3
(20.2 mg, 0.2 mmol) were employed to afford 44.5 mg (87%) of the
indicated product: 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 1.2 Hz,
1H), 7.22 (m, 3H), 7.15 (m, 3H), 6.96 (m, 2H), 6.45 (d, J = 1.2 Hz,
1H); 13C NMR (100 MHz, CDCl3) δ 158.3 (d, J = 244.6 Hz, C),
152.7 (d, J = 244.5 Hz, C), 145.0 (C), 141.5 (CH), 130.0 (C), 129.0
(t, J = 13.6 Hz, C), 128.6 (CH), 128.5 (CH), 127.8 (CH), 117.5 (dd, J
= 22 and 9 Hz, CH), 116.6 (dd, J = 24.1 and 7.5 Hz, CH), 115.9 (d, J
= 25.6 Hz, CH), 107.1 (CH); IR (neat) 3082, 1508, 1433, 1369, 1251,
1180, 1130, 923, 887, 871, 812, 763 cm−1. The spectral data were in
agreement with those reported previously for this compound.67
5-(p-Tolyl)-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole
(10h). Hydrazone Z-7h (67 mg, 0.22 mmol), CuI (42 mg, 0.22
mmol), and NEt3 (22.2 mg, 0.22 mmol) were employed to afford 47.2
1-Phenyl-5-(p-tolyl)-1H-pyrazole (10b). Hydrazone Z-7b (90
mg, 0.38 mmol), CuI (72.2 mg, 0.38 mmol), and NEt3 (39 mg, 0.38
mmol) were employed to afford 76.5 mg (85%) of the indicated
product: 1H NMR (400 MHz, CDCl3) δ 7.74 (d, J = 1.4 Hz, 1H), 7.35
(m, 5H), 7.15 (m, 4H), 6.51 (d, J = 1.5 Hz, 1H), 2.37 (s, 3H); 13C
NMR (100 MHz, CDCl3) δ 143.1 (C), 140.3 (C), 140.2 (CH), 138.1
(C), 129.2 (CH), 128.9 (CH), 128.7 (CH), 127.8 (C), 127.3 (CH),
125.2 (CH), 107.6 (CH), 21.2 (CH3); IR (neat) 3124, 2979, 2869,
1596, 1496, 1446, 1382, 1128, 1072, 1022, 960, 923, 821, 785, 759
cm−1; MS (ESI, m/z) 257.11 [M + Na]+, 235.12 [M + H]+; HRMS
(ESI) calcd. for C16H14N2Na 257.1054 [M + Na]+, found 257.1049;
calcd. for C16H15N2 235.1236 [M + H]+, found 235.1230. The spectral
data were in agreement with those reported previously for this
compound.66
5-(4-Methoxyphenyl)-1-phenyl-1H-pyrazole (10c). Hydra-
zone Z-7c (40 mg, 0.16 mmol), CuI (30.4 mg, 0.16 mmol), and
NEt3 (17 mg, 0.16 mmol) were employed to afford 34 mg (85%) of
the indicated product: 1H NMR (400 MHz, CDCl3) δ 7.68 (d, J = 1.0
Hz, 1H), 7.30 (m, 5H), 7.14 (d, J = 8.67 Hz, 2H), 6.80 (d, J = 8.6 Hz,
2H), 6.43 (d, J = 1.0 Hz, 1H), 3.78 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 159.6 (C), 142.87 (C), 140.3 (C), 140.2 (CH), 130.0 (CH),
128.9 (CH), 127.3 (CH), 125.2 (CH), 123.0 (C), 113.9 (CH), 107.3
(CH), 55.3 (CH3); IR (neat) 3134, 2929, 2835, 1598, 1496, 1442,
1384, 1288, 1245, 1178, 1130, 1029, 960, 925, 835, 786, 759, 692
cm−1. The spectral data were in agreement with those reported
previously for this compound.67
1
mg (71%) of the indicated product: H NMR (400 MHz, CDCl3) δ
7.72 (d, J = 1.4 Hz, 1H), 7.57 (d, J = 8.5 Hz, 2H), 7.42 (d, J = 8.4 Hz,
2H), 7.14 (d, J = 8.3 Hz, 2H), 7.11 (d, J = 8.3 Hz, 2H), 6.48 (d, J = 1.4
Hz, 1H), 2.35 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 143.4 (C),
142.9 (C), 141.0 (CH), 138.7 (C), 129.4 (CH), 129.0 (d, J = 32.5 Hz,
C), 128.7 (CH), 127.4 (C), 125.9 (m, CH), 124.8 (CH), 123.9 (d, J =
270 Hz, C), 108.6 (CH), 21.2 (CH3); IR (neat) 2921, 1616, 1521,
1419, 1379, 1319, 1122, 1060, 956, 920, 844, 817, 777 cm−1; MS (ESI,
m/z) 325.09 [M + Na]+, 303.11 [M + H]+; HRMS (ESI) calcd. for
C17H13F3N2Na 325.0929 [M + Na]+, found 325.0923; calcd. for
C17H14F3N2 303.1109 [M + H]+, found 303.1104.
1-(3-Chloro-4-fluorophenyl)-5-(p-tolyl)-1H-pyrazole (10i).
Hydrazone Z-7i (72 mg, 0.25 mmol), CuI (47.5 mg, 0.25 mmol),
and NEt3 (25.3 mg, 0.25 mmol) were employed to afford 54.7 mg
1
5-Pentyl-1-phenyl-1H-pyrazole (10d). Hydrazone Z-7d (114
mg, 0.53 mmol), CuI (100.7 mg, 0.53 mmol), and NEt3 (53.5 mg, 0.53
mmol) were employed to afford 74.1 mg (65%) of the indicated
(76%) of the indicated product: H NMR (400 MHz, CDCl3) δ 7.70
(d, J = 1.4 Hz, 1H), 7.50 (dd, J = 6.25 and 1.9 Hz, 1H), 7.13 (m, 4H),
7.08 (m, 2H), 6.47 (d, J = 1.6 Hz, 1H), 2.37 (s, 1H); 13C NMR (100
9385
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MHz, CDCl3) δ 157.0 (d, J = 248.5 Hz, C), 143.9 (C), 140.7 (CH),
138.6 (C), 136.8 (C), 129.4 (CH), 128.6 (CH), 127.4 (CH), 127.1
(C), 124.8 (d, J = 6.9 Hz, CH), 121.4 (d, J = 19.7 Hz, C), 116.5 (d, J =
22.7 Hz, CH), 107.9 (CH), 21.2 (CH3); IR (neat) 3066, 2923, 1496,
1417, 1257, 1220, 1136, 1082, 1058, 970, 923, 887, 817, 781, 713
cm−1; MS (ESI, m/z) 309.06 [M + Na]+, 287.08 [M + H]+; HRMS
(ESI) calcd. for C16H12ClFN2Na 309.0571 [M + Na]+, found
309.0565; calcd. for C16H13ClFN2 287.0751 [M + H]+, found
287.0746.
and NEt3 (26 mg, 0.25 mmol) were employed to afford 62.3 mg
(89%) of the indicated product: H NMR (400 MHz, CDCl3) δ 7.71
1
(d, J = 8.31 Hz, 2H), 7.59 (s, 1H), 7.56 (d, J = 8.3 Hz, 2H), 6.23 (s,
1H), 2.67 (t, J = 7.82 Hz, 2H), 1.60 (p, J = 7.3 Hz, 2H), 1.28 (m, 4H),
0.84 (t, J = 6.7 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 144.0 (C),
142.9 (C), 140.6 (CH), 129.6 (q, J = 33.1 Hz, C), 126.3 (m, CH),
125.1 (CH), 123.9 (d, J = 270 Hz, C), 106.3 (CH), 31.3 (CH2), 28.5
(CH2), 26.4 (CH2), 22.3 (CH2), 13.8 (CH3); IR (neat) 2958, 2931,
2862, 1618, 1523, 1463, 1419, 1394, 1321, 1164, 1122, 1064, 1010,
923, 844, 781 cm−1; MS (ESI, m/z) 305.12 [M + Na]+, 283.14 [M +
H]+; HRMS (ESI) calcd. for C15H17F3N2Na 305.1240 [M + Na]+,
found 305.1236; calcd. for C15H18F3N2 283.1422 [M + H]+, found
283.1417.
1-(2,5-Difluorophenyl)-5-(p-tolyl)-1H-pyrazole (10j). Hydra-
zone Z-10j (65 mg, 0.24 mmol), CuI (45.6 mg, 0.24 mmol), and
NEt3 (25 mg, 0.24 mmol) were employed to afford 61.8 mg (95%) of
the indicated product: 1H NMR (400 MHz, CDCl3) δ 7.75 (d, J = 1.0
Hz, 1H), 7.20 (m, 1H), 7.09 (m, 4H), 7.02 (m, 2H), 6.48 (d, J = 1.0
Hz, 1H), 2.31 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 158.2 (d, J =
244 Hz, C), 152.8 (d, J = 247.3 Hz, C), 145.1 (C), 141.4 (CH), 138.5
(C), 129.3 (CH), 129.2 (t, J = 10.8 Hz, C), 127.7 (CH), 127.1 (CH),
117.5 (dd, J = 22.4, 9 Hz, CH), 116.5 (dd, J = 23.2, 7.7 Hz, CH), 115.9
(d, J = 25.8 Hz, CH), 106.9 (CH), 21.2 (CH3); IR (neat) 3074, 2869,
2623, 1508, 1469, 1433, 1365, 1257, 1180, 1130, 923, 871, 821, 788,
765 cm−1; MS (ESI, m/z) 293.09 [M + Na]+, 271.10 [M + H]+;
HRMS (ESI) calcd. for C16H12F2N2Na 293.0866 [M + Na]+, found
293.0861; calcd. for C16H13F2N2 271.1047 [M + H]+, found 271.1041.
5-(4-Methoxyphenyl)-1-(4-(trifluoromethyl)phenyl)-1H-pyr-
azole (10k). Hydrazone Z-10k (55 mg, 0.17 mmol), CuI (32.3 mg,
0.17 mmol), and NEt3 (18 mg, 0.17 mmol) were employed to afford
47.9 mg (87%) of the indicated product: 1H NMR (400 MHz, CDCl3)
δ 7.71 (d, J = 1.2 Hz 1H), 7.57 (d, J = 8.5 Hz, 2H), 7.42 (d, J = 8.4 Hz,
2H), 7.14 (d, J = 8.5 Hz, 2H), 6.85 (d, J = 8.8 Hz, 2H), 6.44 (d, J = 1
Hz, 1H), 3.80 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 159.9 (C),
143.2 (C), 142.9 (C), 141.0 (CH), 130.1 (CH), 129.1 (q, J = 32.5 Hz,
C), 126.0 (m, CH), 124.8 (CH), 123.9 (d, J = 270 Hz, C), 122.6 (C),
114.2 (CH), 108.4 (CH), 55.3 (CH3); IR (neat) 2846, 1614, 1521,
1498, 1456, 1419, 1384, 1323, 1251, 1161, 1120, 1101, 1062, 1029,
960, 923, 837, 792 cm−1; MS (ESI, m/z) 341.09 [M + Na]+, 319.11
[M + H]+; HRMS (ESI) calcd. for C17H13F3N2NaO 341.0878 [M +
Na]+, found 341.0872; calcd. for C17H14F3N2O 319.1058 [M + H]+,
found 319.1053.
1-(3-Chloro-4-fluorophenyl)-5-pentyl-1H-pyrazole (10o).
Hydrazone Z-7o (60 mg, 0.23 mmol), CuI (43.7 mg, 0.23 mmol),
and NEt3 (23.2 mg, 0.23 mmol) were employed to afford 34.2 mg
1
(57%) of the indicated product: H NMR (400 MHz, CDCl3) δ 7.54
(s, 1H), 7.51 (m, 1H), 7.27 (m, 1H), 7.21 (t, J = 8.6 Hz, 1H), 6.18 (s,
1H), 2.59 (t, J = 7.8 Hz, 2H), 1.57 (p, J = 7.4 Hz, 2H), 1.27 (m, 4H),
0.84 (t, J = 6.8 Hz, 3H); 13C NMR (100 MHz, CDCl3) δ 157.4 (J =
248.5 Hz, C), 144.0 (C), 140.3 (CH), 136.6 (C), 127.8 (CH), 125.0
(d, J = 9.5 Hz, CH), 121.6 (d, J = 18 Hz, C), 116.7 (d, J = 22.7 Hz,
CH), 105.8 (CH), 31.3 (CH2), 28.4 (CH2), 26.1 (CH2), 22.3 (CH2),
13.8 (CH3); IR (neat) 2956, 2929, 2860, 1598, 1504, 1463, 1413,
1259, 1222, 1064, 923, 879, 819, 781, 731 cm−1. MS (ESI, m/z)
289.09 [M + Na]+, 267.11 [M + H]+; HRMS (ESI) calcd. for
C14H16ClFN2Na 289.0883 [M + Na]+, found 289.0878; calcd. for
C14H17ClFN2 267.1065 [M + H]+, found 267.1059.
1-(2,5-Difluorophenyl)-5-pentyl-1H-pyrazole (10p). Hydra-
zone Z-7p (50 mg, 0.20 mmol), CuI (38 mg, 0.20 mmol), and
NEt3 (20.2 mg, 0.20 mmol) were employed to afford 42.5 mg (85%)
of the indicated product: 1H NMR (400 MHz, CDCl3) δ 7.59 (s, 1H),
7.14 (m, 2H), 7.05 (m, 1H), 6.17 (s, 1H), 2.49 (t, J = 7.73 Hz, 2H),
1.54 (p, 2H), 1.23 (m, 4H), 0.81 (t, 3H); 13C NMR (100 MHz,
CDCl3) δ 158.2 (d, J = 244 Hz, C), 153.2 (d, J = 249.3 Hz, C), 145.6
(C), 141.0 (CH), 128.5 (m, C), 117.3 (dd, J = 22.7 and 9 Hz, CH),
116.8 (dd, J = 23.4 and 7.7 Hz, CH), 116.2 (d, J = 24.8 Hz, CH),
105.0 (CH), 31.2 (CH2), 28.1 (CH2), 25.4 (CH2), 22.2 (CH2), 13.8
(CH3); IR (neat) 2956, 2931, 2862, 1625, 1596, 1510, 1458, 1377,
1251, 1174, 923, 894, 867, 813, 763 cm−1; MS (ESI, m/z) 273.12 [M
+ Na]+, 251.14 [M + H]+; HRMS (ESI) calcd. for C14H16F2N2Na
273.1178 [M + Na]+, found 273.1174; calcd. for C14H17F2N2 251.1360
[M + H]+, found 251.1354.
3-Methyl-5-phenyl-1-(4-(trifluoromethyl)phenyl)-1H-pyra-
zole (10q). Hydrazone Z-7q (70 mg, 0.23 mmol), CuI (43.7 mg,
0.25 mmol), and NEt3 (23.2 mg, 0.25 mmol) were employed to afford
54.6 mg (78%) of the indicated product: 1H NMR (400 MHz, CDCl3)
δ 7.46 (d, J = 8.4 Hz, 2H), 7.30 (d, J = 8.4 Hz, 2H), 7.24 (m, 3H),
7.14 (m, 2H), 6.23 (s, 1H), 2.29 (s, 3H); 13C NMR (100 MHz,
CDCl3) δ 150.4 (C), 144.0 (C), 142.9 (C), 130.5 (C), 129.0 (q, J =
9.1 Hz, C), 128.7 (CH), 128.6 (CH), 128.5 (CH), 125.9 (m, CH),
124.6 (CH), 124.6 (d, J = 270 Hz, C), 108.9 (CH), 13.5 (CH3); IR
(neat) 3060, 2925, 2850, 1616, 1519, 1496, 1448, 1411, 1361, 1323,
1162, 1105, 1062, 1036, 966, 840, 760 cm−1; MS (ESI, m/z) 325.09
[M + Na]+, 303.11 [M + H]+; HRMS (ESI) calcd. for C17H13F3N2Na
325.0929 [M + Na]+, found 325.0923; calcd. for C17H14F3N2 303.1109
[M + H]+, found 303.1104.
1-(3-Chloro-4-fluorophenyl)-5-(4-methoxyphenyl)-1H-pyra-
zole (10l). Hydrazone Z-7l (50 mg, 0.17 mmol), CuI (32.3 mg, 0.17
mmol), and NEt3 (18 mg, 0.17 mmol) were employed to afford 48 mg
1
(96%) of the indicated product: H NMR (400 MHz, CDCl3) δ 7.67
(d, J = 1.5 Hz, 1H), 7.48 (m, 1H), 7.14 (d, J = 8.6 Hz, 2H), 7.07 (m,
2H), 6.85 (d, J = 8.6 Hz, 2H), 6.43 (d, J = 1.3 Hz, 1H), 3.80 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 159.9 (C), 157.0 (d, J = 248.3 Hz, C),
143.1 (C), 140.7 (CH), 136.9 (C), 130.0 (CH), 127.4 (CH), 124.7 (d,
J = 7.1 Hz, CH), 122.4 (C), 121.4 (d, J = 19.3 Hz, C), 116.5 (d, J =
22.6 Hz, CH), 114.2 (CH), 107.7 (CH), 55.3 (CH3); IR (neat) 2960,
2840, 1610, 1548, 1496, 1467, 1442, 1419, 1375, 1301, 1245, 1174,
1134, 1080, 1028, 966, 923, 875, 833, 790, 719 cm−1; MS (ESI, m/z)
325.05 [M + Na]+, 303.07 [M + H]+; HRMS (ESI) calcd. for
C16H12ClFN2NaO 325.0520 [M + Na]+, found 325.0514; calcd. for
C16H13ClFN2O 303.0700 [M + H]+, found 303.0695.
1-(2,5-Difluorophenyl)-5-(4-methoxyphenyl)-1H-pyrazole
(10m). Hydrazone Z-7m (70 mg, 0.24 mmol), CuI (45.6 mg, 0.24
mmol), and NEt3 (24.3 mg, 0.24 mmol) were employed to afford 60.2
1
mg (86%) of the indicated product: H NMR (400 MHz, CDCl3) δ
7.72 (br s, 1H), 7.19 (m, 1H), 7.13 (d, J = 8.3 Hz, 2H), 7.02 (m, 2H),
6.80 (d, J = 8.5 Hz, 2H), 6.45 (s,1H), 3.76 (s, 3H); 13C NMR (100
MHz, CDCl3) δ 159.8 (C), 158.2 (d, J = 244.3 Hz, C), 152.8 (d, J =
248.5 Hz, C), 144.9 (C), 141.4 (CH), 129.2 (CH), 129.0 (C), 122.4
(C), 117.5 (dd, J = 22 and 9 Hz, CH), 116.5 (dd, J = 24.3 and 7.5 Hz,
CH), 115.9 (d, J = 25.8 Hz, CH), 114.0 (CH), 106.6 (CH), 55.2
(CH3); IR (neat) 3136, 3076, 2972, 2842, 1614, 1573, 1508, 1494,
1434, 1365, 1249, 1178, 1026, 925, 875, 835, 790, 765 cm−1; MS (ESI,
m/z) 309.08 [M + Na]+, 287.10 [M + H]+; HRMS (ESI) calcd. for
C16H12F2N2NaO 309.0815 [M + Na]+, found 309.0810; calcd. for
C16H13F2N2O 287.0996 [M + H]+, found 287.0990.
1-(3-Chloro-4-fluorophenyl)-3-methyl-5-phenyl-1H-pyrazole
(10r). Hydrazone Z-7r (70 mg, 0.25 mmol), CuI (47.5 mg, 0.25
mmol), and NEt3 (25 mg, 0.25 mmol) were employed to afford 37.8
1
mg (54%) of the indicated product: H NMR (400 MHz, CDCl3) δ
7.48 (d, J = 5.5 Hz, 1H), 7.35 (m, 3H), 7.24 (m, 2H), 7.05 (m, 2H),
6.32 (s, 1H), 2.39 (s, 3H); 13C NMR (100 MHz, CDCl3) δ 156.9 (J =
248.3 Hz, C), 149.9, 143.9, 136.7, 131.4, 130.2, 128.6, 128.5, 127.2,
124.6 (d, J = 7.3 Hz), 121.3, 116.4 (d, J = 22.8 Hz), 108.2, 13.5; IR
(neat) 3062, 2923, 1602, 1556, 1504, 1452, 1404, 1363, 1259, 1226,
1191, 1080, 1055, 1016, 977, 910, 875, 817, 759 cm−1; MS (ESI, m/z)
309.06 [M + Na]+, 287.08 [M + H]+; HRMS (ESI) calcd. for
C16H12ClFN2Na 309.0571 [M + Na]+, found 309.0565; calcd. for
C16H13ClFN2 287.0751 [M + H]+, found 287.0746.
5-Pentyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole (10n).
Hydrazone Z-7n (70 mg, 0.25 mmol), CuI (47.5 mg, 0.25 mmol),
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Article
1-(2,5-Difluorophenyl)-3-methyl-5-phenyl-1H-pyrazole
(10s). Hydrazone Z-7s (68 mg, 0.25 mmol), CuI (47.5 mg, 0.25
mmol), and NEt3 (25 mg, 0.25 mmol) were employed to afford 52.4
for C21H14F2N2Na 355.1023 [M + Na]+, found 355.1017; calcd. for
C21H15F2N2 333.1203 [M + H]+, found 333.1198.
5-Ferrocenyl-1-phenyl-1H-pyrazole (10x). Hydrazone Z-7x
(72 mg, 0.22 mmol), CuI (41.8 mg, 0.22 mmol), and NEt3 (22.2
mg, 0.22 mmol) were employed to afford 31.7 mg (44%) of the
1
mg (77%) of the indicated product: H NMR (400 MHz, CDCl3) δ
7.30 (m, 3H), 7.23 (m, 3H), 7.02 (m, 2H), 6.35 (s, 1H), 2.39 (s, 3H);
13C NMR (100 MHz, CDCl3) δ 158.2 (d, J = 241.5 Hz, C), 152.8 (d, J
1
indicated product: H NMR (400 MHz, CDCl3) δ 7.62 (s, 1H), 7.40
(m, 5H), 6.50 (s,1H), 4.17 (s, 2H), 4.14 (s, 2H), 4.05 (s, 5H); 13C
NMR (100 MHz, CDCl3) δ 141.5 (C), 140.4 (C), 140.0 (CH), 128.8
(CH), 128.0 (CH), 126.1 (CH), 106.8 (CH), 75.1 (C), 69.9 (CH),
68.8 (CH), 68.6 (CH). The spectral data were in agreement with
those reported previously for this compound.26
= 248.5 Hz, C), 150.7 (C), 145.8 (C), 130.2 (C), 129.1 (t, J = 10.6 Hz,
C), 128.5 (CH), 128.4 (CH), 127.7 (CH), 117.4 (dd, J = 9.2 and 22.9
Hz, CH), 116.3 (dd, J = 23.9 and 7.5 Hz, CH), 115.8 (d, J = 25.1 Hz,
CH), 107.1 (CH), 13.6 (CH3); IR (neat) 3080, 2925, 1623, 1556,
1508, 1496, 1359, 1251, 1201, 1174, 1014, 981, 889, 871, 819, 800,
761 cm−1; MS (ESI, m/z) 293.09 [M + Na]+, 271.10 [M + H]+;
HRMS (ESI) calcd. for C16H12F2N2Na 293.0861 [M + Na]+, found
293.0861; calcd. for C16H13F2N2 271.1047 [M + H]+, found 271.1041.
1,3,5-Triphenyl-1H-pyrazole (10t). Hydrazone Z-7t (70 mg,
0.24 mmol), CuI (45.6 mg, 0.24 mmol), and NEt3 (24 mg, 0.24
mmol) were employed to afford 69.3 mg (99%) of the indicated
product: 1H NMR (400 MHz, CDCl3) δ 8.0 (d, J = 7.4 Hz, 2H), 7.49
(t, J = 7.5 Hz, 2H), 7.43 (m, 3H), 7.35 (m, 8H), 6.88 (s, 1H); 13C
NMR (100 MHz, CDCl3) δ 152.0 (C), 144.5 (C), 140.3 (C), 133.2
(C), 130.7 (C), 128.9 (CH), 128.8 (CH), 128.7 (CH), 128.5 (CH),
128.3 (CH), 128.0 (CH), 127.4 (CH), 125.9 (CH), 125.4 (CH),
105.3 (CH); IR (neat) 3120, 2923, 1595, 1494, 1456, 1361, 1213,
1174, 1066, 970, 920, 791 cm−1; MS (ESI, m/z) 297.14 [M + H]+;
HRMS (ESI) calcd. for C21H17N2 297.1392 [M + H]+, found
297.1386.
5-Ferrocenyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole
(10y). Hydrazone Z-7y (78 mg, 0.20 mmol), CuI (38 mg, 0.20
mmol), and NEt3 (20.2 mg, 0.20 mmol) were employed to afford 64.7
1
mg (83%) of the indicated product: H NMR (400 MHz, CDCl3) δ
7.67 (s, 1H), 7.64 (d, J = 7.3 Hz, 2H), 7.49 (d, J = 7.2 Hz, 2H), 6.51
(s, 1H), 4.32 (s, 2H), 4.28 (s, 2H), 4.18 (s, 5H); 13C NMR (100 MHz,
CDCl3) δ 143,0 (C), 141.7 (C), 140.8 (CH), 129.3 (q, J = 32.3 Hz,
C), 125.8 (m, CH), 123.8 (d, J = 270.5 Hz, C), 108.7 (CH), 75.9 (C),
70.6 (CH), 69.8 (CH), 69.4 (CH); IR (neat) 1614, 1521, 1411, 1396,
1384, 1321, 1226, 1174, 1157, 1136, 1107, 1085, 1066, 1004, 972, 920,
871, 846, 817, 790 cm−1; MS (ESI, m/z) 419.04 [M + Na]+, 397.06
[M + H]+, 396.05 [M]+; HRMS (ESI) calcd. for C20H15F3FeN2Na
419.0433 [M + Na]+, found 419.0429; calcd. for C20H16F3FeN2
397.0615 [M + H]+, found 397.0610; calcd. for C20H15F3FeN2
+
396.0536 [M] , found 396.0537.
3,5-Diphenyl-1-(4-(trifluoromethyl)phenyl)-1H-pyrazole
(10u). Hydrazone Z-7u (47 mg, 0.13 mmol), CuI (24.7 mg, 0.13
mmol), and NEt3 (13 mg, 0.13 mmol) were employed to afford 41.4
1-(3-Chloro-4-fluorophenyl)-5-ferrocenyl-1H-pyrazole
(10z). Hydrazone Z-7z (60 mg, 0.16 mmol), CuI (30.4 mg, 0.16
mmol), and NEt3 (17 mg, 0.16 mmol) were employed to afford 40.2
1
mg (88%) of the indicated product: H NMR (400 MHz, CDCl3) δ
1
mg (67%) of the indicated product: H NMR (400 MHz, CDCl3) δ
7.83 (d, J = 7.3 Hz, 2H), 7.49 (d, J = 8.4 Hz, 2H), 7.40 (d, J = 8.4 Hz,
2H), 7.34 (t, J = 7.4 Hz, 2H), 7.27 (m, 4H), 7.20 (m, 2H), 6.74 (s,
1H); 13C NMR (100 MHz, CDCl3) δ 152.7 (C), 144.7 (C), 142.9
(C), 132.7 (C), 130.3 (C), 129.0 (d, J = 33 Hz, C), 128.85 (CH),
128.8 (CH), 128.7 (CH), 128.3 (CH), 128.0 (CH), 126.0 (m, CH),
125.9 (CH), 124.8 (CH), 123.9 (d, J = 270 Hz, C), 106.3 (CH); IR
(neat) 3064, 1612, 1550, 1523, 1483, 1458, 1409, 1363, 1323, 1166,
1107, 1056, 1016, 968, 916, 846, 810, 763 cm−1; MS (ESI, m/z)
387.11 [M + Na]+, 365.13 [M + H]+; HRMS (ESI) calcd. for
C22H15F3N2Na 387.1085 [M + Na]+, found 387.1080; calcd. for
C22H16F3N2 365.1266 [M + H]+, found 365.1260.
7.62 (s, 1H), 7.50 (m, 1H), 7.17 (m, 2H), 6.48 (s, 1H), 4.29 (s, 2H),
4.23 (s, 2H), 4.15 (s, 5H); 13C NMR (100 MHz, CDCl3) δ 157.3 (d, J
= 248.5 Hz, C), 1441.8 (C), 140.5 (CH), 136.9 (C), 128.1 (CH),
125.5 (d, J = 7.2 Hz, CH), 121.2 (d, J = 18.8 Hz, C), 116.4 (d, J = 22.5
Hz, CH), 107.5 (CH), 75.1 (C), 70.2 (CH), 69.2 (2 × CH); IR (neat)
3043, 1600, 1562, 1502, 1407, 1263, 1215, 1143, 1107, 1085, 1062,
1024, 1002, 975, 921, 867, 815, 783 cm−1; MS (ESI, m/z) 403.01 [M
+ Na]+, 381.03 [M + H]+, 380.02 [M]+; HRMS (ESI) calcd. for
C19H14ClFFeN2Na 403.0076 [M + Na]+, found 403.0072; calcd. for
C19H15ClFFeN2 381.0258 [M + H]+, found 381.0152; calcd. for
C19H14ClFFeN2 380.0179 [M]+, found 380.0179.
1-(2,5-Difluorophenyl)-5-ferrocenyl-1H-pyrazole (10aa). Hy-
drazone Z-7aa (70 mg, 0.20 mmol), CuI (38 mg, 0.20 mmol), and
NEt3 (20.2 mg, 0.20 mmol) were employed to afford 60.2 mg (86%)
of the indicated product: 1H NMR (400 MHz, CDCl3) δ 7.70 (s, 1H),
7.17 (m, 3H), 6.51 (s, 1H), 4.24 (s, 4H), 4.11 (s, 5H); 13C NMR (100
MHz, CDCl3) δ 158.1 (d, J = 244.6 Hz, C), 153.9 (d, J = 250.9 Hz, C),
143.6 (C), 141.2 (CH), 129.0 (m, C), 117.3 (m, 2 × CH), 116.6 (d, J
= 25.2 Hz, CH), 105.9 (CH), 74.1 (C), 69.9 (CH), 69.0 (CH), 67.7
(CH); IR (neat) 3083, 2989, 2869, 1625, 1508, 1473, 1454, 1415,
1253, 1180, 1141, 1103, 999, 925, 879, 819, 794, 765 cm−1; MS (ESI,
m/z) 387.04 [M + Na]+, 365.06 [M + H]+; HRMS (ESI) calcd. for
C19H14F2FeN2Na 387.0371 [M + Na]+, found 387.0367; calcd. for
C19H15F2FeN2 365.0553 [M + H]+, found 365.0547.
1-(3-Chloro-4-fluorophenyl)-3,5-diphenyl-1H-pyrazole
(10v). Hydrazone Z-7v (50 mg, 0.14 mmol), CuI (26.6 mg, 0.14
mmol), and NEt3 (15 mg, 0.14 mmol) were employed to afford 47.5
1
mg (95%) of the indicated product: H NMR (400 MHz, CDCl3) δ
7.92 (d, J = 6.8 Hz, 2H), 7.59 (m, 1H), 7.46 (m, 2H), 7.39 (m, 4H),
7.30 (m, 2H), 7.15 (m, 1H), 7.08 (m, 1H), 6.83 (s, 1H); 13C NMR
(100 MHz, CDCl3) δ 157.1 (d, J = 248.5 Hz, C), 152.5 (C), 144.6
(C), 136.8 (C), 136.7 (CH), 132.7 (C), 130.1 (C), 128.8 (CH), 128.7
(2 × CH), 128.5 (CH), 127.8 (CH), 125.9 (CH), 124.8 (d, J = 7.5 Hz,
CH), 121.4 (d, J = 19.5 Hz, C), 116.5 (d, J = 21.8 Hz, CH), 105.7
(CH); IR (neat) 3060, 1602, 1550, 1498, 1460, 1402, 1363, 1257,
1230, 1209, 1178, 1072, 1028, 979, 954, 908, 875, 852, 817, 758 cm−1
;
MS (ESI, m/z) 371.07 [M + Na]+, 349.09 [M + H]+; HRMS (ESI)
calcd. for C21H14ClFN2Na 371.0727 [M + Na]+, found 371.0722;
calcd. for C21H15ClFN2 349.0908 [M + H]+, found 349.0902.
1-(2,5-Difluorophenyl)-3,5-diphenyl-1H-pyrazole (10w). Hy-
drazone Z-7w (75 mg, 0.23 mmol), CuI (43.7 mg, 0.23 mmol), and
NEt3 (23.2 mg, 0.23 mmol) were employed to afford 73.5 mg (98%)
ASSOCIATED CONTENT
■
S
* Supporting Information
1
1
Figures giving H and 13C NMR spectra of new acetylenic
of the indicated product: H NMR (400 MHz, CDCl3) δ 7.95 (d, J =
7.5 Hz, 2H), 7.47 (t, J = 7.4 Hz, 2H), 7.35 (m, 7H), 7.06 (m, 2H),
6.88 (s, 1H); 13C NMR (100 MHz, CDCl3) δ 158.3 (d, J = 243.8, Hz,
C), 153.2 (C), 152.8 (d, J = 247 Hz, C), 146.5 (C), 132.7 (C), 130.0
(C), 129.8 (t, J = 14.3 Hz, C), 128.7 (CH), 128.65 (CH), 128.6 (CH),
128.3 (CH), 127.8 (CH), 125.9 (CH), 117.5 (dd, J = 22 and 9.1 Hz,
CH), 116.6 (dd, J = 23.2 and 7.6 Hz, CH), 116.0 (d, J = 25.5 Hz,
CH), 104.6 (CH); IR (neat) 3078, 1625, 1602, 1546, 1508, 1487,
1456, 1359, 1253, 1215, 1176, 1076, 954, 889, 869, 812, 758 cm−1; MS
(ESI, m/z) 355.10 [M + Na]+, 333.12 [M + H]+; HRMS (ESI) calcd.
hydrazones and pyrazoles. This material is available free of
charge via Internet at http://pubs.acs.org.
AUTHOR INFORMATION
■
Corresponding Author
*Tel.: +90-312-2103213. Fax: +90-312-2103200. E-mail: zora@
metu.edu.tr.
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Article
(12) Sliskovic, D. R.; Roth, B. D.; Wilson, M. W.; Hoefle, M. L.;
Newton, R. S. J. Med. Chem. 1990, 33, 31.
ACKNOWLEDGMENTS
■
We thank the Scientific and Technical Research Council of
Turkey (110T113) and the Research Board of Middle East
Technical University (METU) (BAP-2011-07-02-00-01) for
(13) (a) Bauer, V. J.; Dalalian, H. P.; Fanshawe, W. J.; Safir, S. R.;
Tocus, E. C.; Boshart, C. R. J. Med. Chem. 1968, 11, 981. (b) Kees, K.
L.; Fitzgerald, J. J.; Steiner, K. E.; Mattes, J. F.; Mihan, B.; Tosi, T.;
Mondoro, D.; McCaleb, M. L. J. Med. Chem. 1996, 39, 3920.
(14) Almansa, C.; Gomez, L. A.; Cavalcanti, F. L.; Arriba, A. F.;
Rafanell, J. D.; Form, J. G. J. Med. Chem. 1997, 40, 547.
financial support of this research and METU Faculty
̈
Development Program (OYP-Yuzuncu Yıl University) for a
̈
̈
̈
scholarship to A.K.
(15) (a) Stauffer, S. R.; Katzenellenbogen, J. A. J. Comb. Chem. 2000,
2, 318. (b) Stauffer, S. R.; Coletta, C. J.; Tedesco, R.; Nishiguchi, G.;
Carlson, K.; Sun, J.; Katzenellenbogen, B. S.; Katzenellenbogen, J. A. J.
Med. Chem. 2000, 43, 4934. (c) Stauffer, S. R.; Huang, Y.; Coletta, C.
J.; Tedesco, R.; Katzenellenbogen, J. A. Bioorg. Med. Chem. 2001, 9,
141. (d) Penning, T. D.; Khilevich, A.; Chen, B. B.; Russell, M. A.;
Boys, M. L.; Wang, Y.; Duffin, T.; Engleman, V. W.; Finn, M. B.;
Freeman, S. K.; Hanneke, M. L.; Keene, J. L.; Klover, J. A.; Nickols, G.
A.; Nickols, M. A.; Rader, R. K.; Settle, S. L.; Shannon, K. E.;
Steininger, C. N.; Westlin, M. M.; Westlin, W. F. Bioorg. Med. Chem.
Lett. 2006, 16, 3156.
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Chem. Lett. 1996, 6, 1819. (b) Dale, D. J.; Dunn, P. J.; Golightly, C.;
Hughes, M. L.; Levett, P. C.; Pearce, A. K.; Searle, P. M.; Ward, G.;
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