Regioselective three-component synthesis of highly fluorescent 1,3,5-trisubstituted pyrazoles

Article abstract of DOI:10.1002/ejoc.200800444

3,5-Disubstituted and 1,3,5-trisubstituted pyrazoles are readily synthesized from acyl chlorides, terminal alkynes, and hydrazines by a consecutive one-pot three-component Sonogashira coupling/Michael addition/cyclocondensation sequence in good to excelle

Full text of DOI:10.1002/ejoc.200800444

FULL PAPER
DOI: 10.1002/ejoc.200800444
Regioselective Three-Component Synthesis of Highly Fluorescent
1,3,5-Trisubstituted Pyrazoles
Benjamin Willy[a] and Thomas J. J. Müller*[a]
Keywords: C–C coupling / Cyclocondensation / Fluorescence / Microwave reactions / Multi-component reactions / Pyr-
azoles
3,5-Disubstituted and 1,3,5-trisubstituted pyrazoles are read-
ily synthesized from acyl chlorides, terminal alkynes, and hy-
drazines by a consecutive one-pot three-component Sonoga-
shira coupling/Michael addition/cyclocondensation se-
quence in good to excellent yields. These pyrazoles are
highly fluorescent, both in solution and in the solid state. In-
vestigation of the electronic properties by UV/Vis and fluo-
rescence spectroscopy and by DFT and ZINDO CI computa-
tions reveal that the excited state is highly polar and allows
fine-tuning of the absorption and emission properties. X-ray
structure analyses of 3,5-disubstituted pyrazoles reveal self-
organization by hydrogen bonding and π-stacking.
(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim,
Germany, 2008)
cess that has been known for more than a century.[17] Nei-
ther the regioselectivity issue has been studied in detail, nor
was the occurrence of mixtures of regioisomers reported.[18]
Despite of very few examples,[19] the regioselective forma-
tion of N-substituted pyrazoles by the alkynone pathway
has remained unexplored (Scheme 1). With respect to the
interesting electronic properties of pyrazoles as fluoro-
phores and the increasing quest for tailor-made functional
π-electron systems by diversity-oriented strategies,[20] as
part of our program to develop multi-component syntheses
of heterocycles,[21] we have focused on one-pot syntheses of
substituted pyrazoles. Here, we report on a concise, regiose-
lective consecutive three-component synthesis of pyrazoles
with a highly flexible substitution pattern and their absorp-
tion and emission properties.
Introduction
Pyrazoles are five-membered heterocycles with two adja-
cent nitrogen atoms with a rich chemistry and numerous
applications.[1] A broad spectrum of biological activity, such
as antihyperglycemic, analgesic, antiinflammatory, antipy-
retic, antibacterial and sedative-hypnotic activity has at-
tracted considerable interest.[2–4] In addition, several 3,5-di-
aryl-substituted pyrazoles also reversibly inhibit mono-
amine oxidase-A and monoamine oxidase-B.[5] For crop
protection 1,2-dialkyl-3,5-diphenylpyrazoles are known as
potent herbicides.[6] Furthermore, pyrazoles are omnipres-
ent as ligands in coordination chemistry,[7] as building
blocks in heterocycle synthesis,[8] as optical brighteners[9]
and UV stabilizers,[10] as photoinduced electron-transfer
systems,[11] and as units in supramolecular entities.[12]
Hence, numerous methods for the synthesis of 1,3,5-substi-
tuted pyrazoles have been established.[1,13] Among the most
frequently used methods is the cyclocondensation of 1,3-
dicarbonyl compounds, or equivalent 1,3-bis(electrophilic)
reagents such as epoxy ketones, with hydrazines. However,
for substituted hydrazines the product formation often re-
sults in mixtures of regioisomeric pyrazoles (Scheme 1).[14]
Alternatively, besides several regioselective methods[15] sub-
stituted hydrazines can react with α,β-unsaturated ketones
in a regioselective fashion to give pyrazolines, that can be
oxidized to the corresponding pyrazoles.[16] The direct con-
version of hydrazines to pyrazoles can also be achieved by
Michael addition/cyclocondensation to alkynones, a pro-
Scheme 1. Variable regioselectivity in pyrazole formation de-
pending on 1,3-diketones and alkynones as C3 building blocks.
Results and Discussion
[a] Institut für Makromolekulare Chemie und Organische Chemie,
Lehrstuhl für Organische Chemie, Heinrich-Heine-Universität
Düsseldorf,
Alkynones are easily accessible by Sonogashira coup-
ling[22] of acyl chlorides with terminal alkynes.[23] Just re-
cently, we reported that in THF as a solvent only 1 equiv.
of triethylamine as the hydrochloric acid scavenging base
Universitätsstr. 1, 40225 Düsseldorf, Germany
Fax: +49-211-8114324
E-mail: ThomasJJ.Mueller@uni-duesseldorf.de
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B. Willy, T. J. J. Müller
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proves to be most favorable for the successful coupling of Michael addition/cyclocondensation step was optimized
even sensitive alkynes such as (trimethylsilyl)acetylene.[24] In under conventional and microwave heating (Table 1). Best
turn, the resulting alkynones are highly reactive and readily results for the formation of pyrazole 4b were achieved after
react in a one-pot fashion with all kinds of binucleophiles dielectric heating in the microwave cavity at 150 °C for
to give various heterocycles. Therefore, upon treating acyl 10 min in the presence of methanol and acetic acid (Table 1,
chlorides 1 with terminal alkynes 2 under modified Sonoga- Entry 6). Hence, in the sense of a consecutive one-pot pro-
shira conditions at room temperature for 1 h to furnish the cess and with the optimized cyclocondensation conditions,
expected alkynones, subsequently, hydrazines 3, methanol the pyrazoles 4 were obtained in good to excellent yields,
and glacial acetic acid were added to the reaction mixture
and heated to give pyrazoles 4 (Scheme 2). Prior to screen-
ing the scope of this sequence, the pyrazole-forming
Table 1. Optimization of the Michael addition/cyclocondensation
step to give pyrazole 4b.
Entry Heating mode T [°C]
t
Solvent
Yield
1
2
3
4
5
6
oil bath
MW
MW
MW
MW
80
3 d
CH3OH
CH3OH
CH3OH
CH3OH
CH3OH
75%
74%
59%
80%
55%
120
120
150
150
150
20 min
10 min
10 min
15 min
Scheme 2. One-pot three-component synthesis of pyrazoles 4.
Table 2. One-pot three-component synthesis of pyrazoles 4.
MW
10 min CH3OH/CH3CO2H 82%
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Highly Fluorescent 1,3,5-Trisubstituted Pyrazoles
Table 2. (Continued)
[a] tBuOH instead of CH3OH. [b] Performed on a 10 mmol scale.
predominantly as colorless crystalline solids (Scheme 2,
Table 2).
Three types of hydrazines were employed in the meth-
odological studies, i.e. hydrazine (R3 = H, Table 2, En-
tries 1–6), methylhydrazine (R3 = Me, Table 2, Entries 7–
16), and arylhydrazines (R3 = aryl, Table 2, Entries 17–21).
In accordance with theory, in every case one of the two
possible regioisomers, depending on the nature of the hy-
drazine substituent R3, was formed preferentially. Only
traces of the other regioisomers could be detected (regiose-
lectivity Ͼ98:Ͻ2). The structures and substitution patterns
of pyrazoles 4 were unambiguously assigned by 1H, 13C and
2D NMR spectroscopy, mass spectrometry and in addition
by X-ray structure analysis of the pyrazoles 4c, 4e and 4l
(Figures 1, 2, and 3, Table 6).
As a consequence of 3,5-substitution (except for 4a and
4g), in the 1H NMR spectra, only one resonance of the Figure 1. Molecular structure and dimer formation of pyrazole 4e.
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gen bonds (between donor and acceptor atoms) are 2.89 Å
long. The distance between the layers of pyrazoles is found
to be 3.43 Å. Interestingly, the strong π–π interactions are
responsible for an almost perfect coplanarity of the 3,5-di-
arylpyrazole (distortion from planarity ca. 3°).
Pyrazole 4c reveals another mode of self-organization by
hydrogen bonding in the solid state (Figure 2). One pyr-
azole molecule bridges with two others leading to infinite
chains by hydrogen bonding. Again, the hydrogen bonds
are 2.89 Å long. In addition, π-stacking of the pyrazoles
results in a columnar superstructure. The intermolecular
distance of the π-stacked pyrazoles is 3.46 Å, i.e. within the
same range as in graphite. The molecular entities are almost
perfectly planar.
N-Substitution rules out the formation of hydrogen
bonding and, hence, pyrazole 4l will not form comparable
supramolecular structures as observed in the previous crys-
tal structures. The position of the methyl substituent is in
perfect agreement with the Michael addition scenario where
the most electron-rich nitrogen atom (adjacent to the
methyl group) attacks the intermediate alkynone at the β-
acetylene carbon center prior to cyclocondensation (Fig-
ure 3). Other than observed for the structure analyses of the
1H-pyrazoles 4c and 4e the aryl substituents in 3- and 5-
position of 4l are distorted from coplanarity by 11° (4-chlo-
rophenyl) and 36° (phenyl) with respect to the central pyr-
azole ring.
Pyrazoles are well known for interesting electronic prop-
erties.[9,10] Therefore, our diversity-oriented approach to
pyrazoles with variable substitution pattern allows a de-
tailed investigation of the electronic properties by UV/Vis
and fluorescence spectroscopy (Table 3). Expectedly, both
absorption and emission properties are strongly effected by
minute substituent variations or conformational biases. In
solution, the absorption maxima λmax,abs of pyrazoles 4 are
found in the near UV between 260 and 385 nm with molar
Figure 2. Bridging by hydrogen bonding and π-stacking in single
crystals of 4c.
extinction coefficients
ε
ranging from 5300 to
106000 Lmol–1 cm–1. Almost all compounds display con-
siderable blue to green fluorescence with emission maxima
between 320 and 380 nm. The fluorescence quantum yields
were determined with p-terphenyl as a standard[26] and vary
between below 1% to 74%. Due to the large Stokes shifts
Figure 3. Molecular structure of pyrazole 4l.
pyrazole core is found. These signals can be easily identified ranging from 4200 to 12300 cm–1, there is almost no overlap
as sharp singlets. Depending on the nature of R3, the shifts between absorption and emission bands of the pyrazoles 4
of these signals may vary and are found between δ = 6.5 (Figure 4), a favorable effect for many applications as fluo-
and 6.7 ppm. The carbon resonances of the pyrazole core rescent dyes.[27]
can be readily assigned. Evidently, the shifts of these reso-
Large Stokes shifts for 3,5-diarylpyrazoles have been re-
nances are even dependent on the electronic nature of R3. ported before[28] and prompted us to study and scrutinize
Signals for the methine nuclei C-4 can be determined at the electronic structure experimentally and computation-
around at δ ≈ 101–105 ppm. With respect to the broad vari- ally. Therefore, the UV/Vis absorption and emission spectra
ation of R1 and R2, the resonances of the two quaternary of compound 4k were recorded in various solvents
carbon nuclei of the pyrazole core appear between δ = 140 (Table 4). The absorption maximum λmax,abs is essentially
and 150 ppm.
independent of the solvent polarity, whereas the shortest-
The solid-state structures of the pyrazoles were studied wavelength emission maximum λmax,em and the fluorescence
by single-crystal X-ray analyses.[25] The 1H-pyrazoles 4c quantum yield Φf reveal positive solvochromicity and high
and 4e are organized in the crystal lattice by hydrogen fluorescence efficiency in more polar solvents. The solid-
bonding and π-stacking. Pyrazole 4e forms layers consti- state fluorescence is almost identical with the fluorescence
tuted by hydrogen-bonded dimers (Figure 1). These hydro- in acetonitrile (Table 4, Entry 7).
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Highly Fluorescent 1,3,5-Trisubstituted Pyrazoles
Table 3. Selected electronic properties (UV/Vis and fluorescence data, fluorescence quantum yields Φ , and Stokes shifts ∆ν) of the
˜
f
pyrazoles 4 and 6.
Compound
Absorption,[a] λmax,abs [nm] (ε [Lmol–1 cm–1])
Emission,[b] λmax,em [nm] (Φf)[c]
Stokes shift ∆ν[d] [cm–1]
˜
4a
4b
4c
4d
4e
4f
4g
4h
4i
289 (4500), 273 (7600)
258 (95900)
283 (8200), 262 (20400)
283 (10700), 258 (36900),
259 (5300)
330 (Ͻ 0.01)
331 (0.32)
331 (0.15)
323 (0.39)
333 (0.74)
320 (0.02)
348 (0.05)
357 (Ͻ 0.01)
379 (Ͻ 0.01)
452 (0.01)
369 (0.35)
331 (0.05)
323 (0.02)
392 (0.56)
392 (0.10)
383 (0.07)
383 (0.02)
460 (0.01)
382 (0.10)
339 (0.09)
341 (0.08)
382 (0.50)
6300
8600
8000
7800
8600
7700
7900
7000
10200
9100
11400
8400
7200
10200
10500
11100
8700
4200
12300
8500
7000
8900
257 (38100)
273 (13500), 247 (10800),
334 (9200), 297 (20400), 286 (58800)
273 (54900), 260 (53300)
320 (18600), 269 (97200)
260 (52400)
4j
4k
4l
280 (35200), 260 (87500)
262 (106400)
4m
4n
4o
4p
4q
4r
4s
4t
280 (49100)
278 (48600)
269 (24600)
348 (1300), 287 (44200).
385 (19100), 295 (98500)
293 (17400), 259 (50700)
263 (10500)
4u
6
275 (34600)
285 (7600)
[a] Recorded in CH2Cl2 at c = 10–3 . [b] Recorded in CH2Cl2 at c = 10–6 . [c] Determined with p-terphenyl as a standard in cyclohexane,
Φ = 0.82. [d] ∆ν = λ
– λmax,em [cm–1].
˜
f
max,abs
The polar nature of the excited state suggested to take a
closer look at the electronic structure of selected pyrazoles.
A pronounced absorptivity as reflected by large molar ex-
tinction coefficients ε can be accounted for by π–π* transi-
tions. Therefore, based upon the starting geometry ex-
tracted from the X-ray structure analysis of 4l, calculations
were carried out on the level of density functional theory
(B3LYP/3-21+** functional[29] for geometry optimization)
as well as on a semi-empirical level (ZINDO CI[30] after
PM3 geometry optimization). To elucidate the influence of
push-pull substitution on the electronic properties in the
ground and the excited state (Table 3, compounds 4n and
4o) computations were carried out for the selected 3,5-di-
aryl-1-methylpyrazoles 4k, 4n, 4o, and for the 3,5-diphenyl
derivative (Table 5, Entry 1).
The λmax values were either calculated from the com-
puted HOMO–LUMO gap (DFT calculations) or produced
by the ZINDO CI program (Table 5). Interestingly, the
cheaper and faster semi-empirical ZINDO CI computation
reproduces the experimental data for the more complex
push-pull systems 4n and 4o better than the more expensive
and slower DFT method. Thus, for computational high-
throughput screening the ZINDO CI calculation can be
considered as a valid tool.
Figure 4. Normalized absorption (solid line) and emission (dotted
line) spectra of pyrazole 4k (recorded in CH2Cl2, 293 K).
Table 4. Solvent dependence of the longest-wavelength absorption
maximum λmax,abs, the shortest-wavelength emission maximum
λmax,em, and the fluorescence quantum yields Φf of compound 4k.
[a]
[b]
Entry
Solvent
Absorption,
λ
Emission,
λ
Φf[c]
max,abs
max,em
[nm]
[nm]
Furthermore, the DFT-computed frontier orbitals of the
push-pull systems 4n (Figure 5) and 4o (Figure 6) clearly
show that the HOMO–LUMO transition is associated with
significant charge transfer character. For system 4n the
charge transfer only occurs within the (p-cyanophenyl)pyr-
azolyl moiety whereas the p-methoxyphenyl substituent
adopts an orthogonal orientation without orbital coeffi-
cients, suggesting the absence of p-electron interaction. In
the system 4o the charge transfer is characterized by a shift
1
2
3
4
5
6
7
cyclohexane
CH2Cl2
dioxane
THF
acetonitrile
ethanol
259
260
260
260
259
257
–
337
369
358
362
377
366
376
0.10
0.35
0.09
0.12
0.64
0.06
–
solid state
[a] Recorded at c = 10–3 . [b] Recorded at c = 10–6 . [c] Deter-
mined with p-terphenyl as standard in cyclohexane, Φf = 0.82.
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Table 5. Comparison of experimentally (recorded in CH2Cl2, T = 293 K) and computationally (B3LYP/3-21+**) functional and
ZINDO CI determined λmax values of selected 3,5-diaryl-1-methylpyrazoles.
Entry
Substitution pattern
Experiment, λmax,exp. [nm]
DFT, λmax,calcd. [nm][a]
ZINDO CI, λmax,calcd. [nm][b]
1
2
3
4
X = Y = H
250[31]
260
280
249
268
265
333
268
268
287
284
X = OCH3, Y = H (4k)
X = CN, Y = OCH3 (4n)
X = OCH3, Y = CN (4o)
278
[a] Calculated from the HOMO–LUMO gap of the DFT computation with the B3LYP/3-21+** functional. [b] ZINDO CI calculation
after PM3 geometry optimization.
of electron density from the p-methoxyphenyl donor moiety
in the HOMO to the p-cyanophenyl acceptor unit in the
LUMO. Thus, in both cases, 4n and 4o, the origin of a pro-
nounced positive solvochromicity of the emission as a con-
sequence of a polar excited state is nicely rationalized. Ex-
pectedly, push-pull substitution causes a redshift in absorp-
tion and emission and can be successfully applied for fine-
tuning of the fluorescence color of 1,3,5-trisubstituted pyr-
azoles. Yet, the pyrazole-inherent polarity has to be consid-
ered. Although, pyrazoles 4n and 4o are almost identical
with respect to numerical absorption and emission, data the
fluorescence efficiencies clearly deviate, revealing that the
substitution pattern of 4n, presumably as a consequence of
a better overlap of HOMO and LUMO, leads to a more
efficient fluorophore in comparison to 4o.
Figure 6. DFT-computed frontier orbitals of pyrazole 4o, LUMO
(top) and HOMO (bottom).
sequentially palladium-catalyzed process[32] lies at hand.
For instance, the Suzuki coupling has been shown to be
highly compatible with Sonogashira catalyst systems and
conditions.[33]
Therefore, upon subsequent reaction of acyl chloride 1a,
(4-bromophenyl)acetylene (2f), and methylhydrazine (3b),
according to the one-pot three-component synthesis of pyr-
azoles, the pyrazole 4i bearing a bromo phenyl substituent
is treated within the same reaction vessel without further
catalyst addition and in the presence of 1.2 equiv. of p-tolyl-
boronic acid (5), potassium carbonate and water under di-
electric heating at 150 °C for 20 min to give the highly fluo-
rescent biphenylylpyrazole 6 in 52% yield (Scheme 3,
Figure 5. DFT-computed frontier orbitals of pyrazole 4n, LUMO
(top) and HOMO (bottom).
The three-component access to 1,3,5-trisubstituted fluo-
rescent pyrazoles is a highly versatile diversity-oriented ap-
proach to fluorophores that can readily be fine-tuned by
building-block diversity. Considering the mild reaction con-
ditions of this three-component Sonogashira coupling/cy-
clocondensation sequence, the expansion to a four-compo-
nent reaction as a level-two functionalization by addressing
the Pd-catalyst system for a second time in the sense of a Scheme 3. One-pot four-component synthesis of pyrazole 6.
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Highly Fluorescent 1,3,5-Trisubstituted Pyrazoles
Table 3). Interestingly, the combined yields of the two-step for crystal engineering as demonstrated by the well-bal-
process, i.e. 60% for the formation of pyrazole 4i and 70% anced interplay of hydrogen bonding and π-stacking giving
for the Suzuki coupling of 4i with 5 to give 6, are lower rise to supramolecular self-organization in crystal lattices.
than the yield of the four-component synthesis. Thus, with Studies addressing this methodology to enhance molecular
four new bonds and a ring formed in a one-pot fashion and diversity in biologically active, electronic and photonic tar-
an average yield of 85% per bond forming step this novel gets are currently underway.
multi-component reaction is perfectly suited for the rapid
assembly of complex structures with a pyrazole core.
Experimental Section
General Considerations: All reactions involving water-sensitive
compounds were carried out in flame-dried glassware under nitro-
Conclusions
A straightforward regioselective, microwave-assisted one-
pot three-component synthesis of 1,3,5-substituted pyr-
azoles was developed in the sense of a consecutive coupling/
cyclocondensation sequence. Furthermore, one example of
an efficient four-component Sonogashira coupling/cy-
clocondensation/Suzuki coupling, a sequentially Pd-cata-
lyzed process, giving rise to a biphenylyl-substituted pyr-
azole could be demonstrated. Expectedly, most pyrazoles
are blue to green light emitting fluorophores that were in-
vestigated by UV/Vis and emission spectroscopy as well as
by computational methods. The rapid, diversity-oriented
synthetic approach to fine-tunable fluorophores can be of
considerable interest for the development of tailor-made
emitters in OLED applications and fluorescence labelling
of biomolecules, surfaces or mesoporous materials. 3,5-Di-
gen unless stated otherwise. Reagents and catalysts were purchased
reagent-grade and used without further purification. Solvents were
dried by a solvent purification system. Flash column chromatog-
raphy: silica gel 60, mesh 230–400. TLC: silica gel plates (60 F254).
1H, 13C, DEPT, NOESY, COSY, HMQC, and HMBC NMR spec-
tra were recorded with a 500 MHz NMR spectrometer by using
CDCl3 as solvent unless stated otherwise. The assignments of qua-
ternary C, CH, CH2 and CH3 were made on the basis of DEPT
spectra. Mass spectra were recorded with a quadruple spectrome-
ter. The melting points are uncorrected. Elemental analyses were
carried out in the microanalytical laboratory of the Pharmazeut-
isches Institut of the Heinrich-Heine-Universität Düsseldorf. Di-
electric heating was performed in a single-mode microwave cavity
producing continuous irradiation at 2450 MHz. For X-ray struc-
ture data of the pyrazoles 4c, 4e and 4l, see Table 6.
General Procedure for the Synthesis of Pyrazoles 4 (GP): In a 10 mL
substituted pyrazoles are highly intriguing building blocks microwave tube PdCl2(PPh3)2 (15 mg, 0.02 mmol) and CuI (8 mg,
Table 6. Crystal data and structure refinement for 4c, 4e and 4l.
Structure
4c
4e
4l
Empirical formula
Formula mass
Temperature [K]
Wavelength [Å]
Crystal system
Space group
Z
C
268.73
200(2)
0.71073
monoclinic
P21/n
16H13ClN2
C16H11F3N2
288.27
200(2)
0.71073
monoclinic
P21/n
C16H13ClN2
268.73
200(2)
0.71073
monoclinic
P21/n
4
4
4
a [Å]
α [°]
15.111(2)
90
14.6850(2)
90
12.5736(13)
90
b [Å]
β [°]
c [Å]
γ [°]
4.8699(8)
93.643(4)
17.599(3)
90
1292.5(4)
1.381
0.281
needle
1.87ϫ0.08ϫ0.06
colorless
1.72–28.31
5.8066(1)
98.766(1)
15.2535(2)
90
1285.47(3)
1.490
7.2414(8)
101.299(2)
14.9816(16)
101.299(2)
1337.6(2)
1.334
Volume [Å3]
Density (calcd.) [g/cm3]
Absorption coefficient µ [mm–1
Crystal shape
Crystal size [mm]
Crystal colour
θ range for data collection [°]
Index ranges
]
0.120
0.272
polyhedron
0.58ϫ0.22ϫ0.20
colorless
1.79–27.49
polyhedron
0.39ϫ0.23ϫ0.16
colorless
1.94–28.31
–16 Յ h Յ 16, –9 Յ k Յ 9, –19
Յ l Յ 19
13547
–19 Յ h Յ 20, –6 Յ k Յ 6, –23 19 Յ h Յ 18, –7 Յ k Յ 7, –19
Յ l Յ 23
12800
Յ l Յ 19
12675
Reflections collected
Independent reflections
Observed reflections [I Ͼ 2σ(I)]
Absorption correction
Max./min. transmission
Refinement method
3213 [R(int) = 0.0354]
2821
2946 [R(int) = 0.0549]
2337
3326 [R(int) = 0.0297]
2976
semi-empirical from equivalents
0.98/0.62
0.98/0.93
0.96/0.90
full-matrix least squares on F2
3213/21/191
Data/restraints/parameters
2946/0/198
1.04
3326/0/173
1.08
Goodness-of-fit on F2
1.25
Final R indices [I Ͼ 2σ(I)]
Largest difference peak/hole [eÅ–3
R1 = 0.064, wR2 = 0.128
0.27/–0.26
R1 = 0.045, wR2 = 0.109
0.24/–0.27
R1 = 0.042, wR2 = 0.109
0.29/–0.32
]
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Table 7. Experimental details for the synthesis of pyrazoles 4.
Entry
Acyl chloride 1 [mg] ([mmol])
Alkyne 2 [mg] ([mmol])
Hydrazine 3 [mg] ([mmol])
Pyrazole 4 [mg] (yield [%])
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
147 (1.00) of 1a
155 (1.00) of 1b
155 (1.00) of 1b
197 (1.00) of 1c
209 (1.00) of 1d
176 (1.00) of 1e
147 (1.00) of 1a
147 (1.00) of 1a
147 (1.00) of 1a
147 (1.00) of 1a
1710 (10.0) of 1f
176 (1.00) of 1e
1760 (10.0) of 1e
166 (1.00) of 1g
171 (1.00) of 1f
210 (1.00) of 1h
147 (1.00) of 1a
147 (1.00) of 1a
176 (1.00) of 1e
176 (1.00) of 1e
176 (1.00) of 1e
99 (1.00) of 2a
103 (1.00) of 2b
137 (1.00) of 2c
103 (1.00) of 2b
103 (1.00) of 2b
83 (1.00) of 2d
99 (1.00) of 2a
148 (1.00) of 2e
192 (1.00) of 2f
308 (1.00) of 2g
1030 (10.0) of 2b
103 (1.00) of 2b
690 (10.0) of 2h
133 (1.00) of 2i
128 (1.00) of 2j
128 (1.00) of 2j
161 (1.00) of 2k
172 (1.00) of 2l
103 (1.00) of 2b
83 (1.00) of 2d
83 (1.00) of 2d
56 (1.10) of 3a[a]
56 (1.10) of 3a[a]
56 (1.10) of 3a[a]
56 (1.10) of 3a[a]
56 (1.10) of 3a[a]
56 (1.10) of 3a[a]
51 (1.10) of 3b
51 (1.10) of 3b
51 (1.10) of 3b
51 (1.10) of 3b
510 (11.0) of 3b
51 (1.10) of 3b
510 (11.0) of 3b
51 (1.10) of 3b
51 (1.10) of 3b
51 (1.10) of 3b
206 (1.10) of 3c
157 (1.10) of 3d
119 (1.10) of 3e
119 (1.10) of 3e
206 (1.10) of 3c
141 (94) of 4a
191 (82) of 4b
143 (53) of 4c
207 (75) of 4d
219 (76) of 4e
194 (83) of 4f
127 (77) of 4g
215 (75) of 4h
180 (60) of 4i
386 (87) of 4j
1752 (93) of 4k
255 (95) of 4l
2246 (95) of 4m
178 (62) of 4n
167 (58) of 4o
194 (59) of 4p
264 (60) of 4q
213 (77) of 4r
271 (81) of 4s
191 (67) of 4t
266 (70) of 4u
[a] As hydrazine monohydrate.
3
0.04 mmol) were dissolved in degassed THF (4 mL). Then, to this
orange solution acyl chloride 1 (1.00 mmol), alkyne 2 (1.00 mmol),
(500 MHz, [D6]acetone): δ = 2.36 (s, 3 H), 7.10 (s, 1 H), 7.28 (d, J
= 8.1 Hz, 2 H), 7.46 (d, 3J = 8.6 Hz, 2 H), 7.75 (d, 3J = 8.1 Hz,
and triethylamine (1.05 mmol) were added. The reaction mixture 2 H), 7.97 (d, J = 8.6 Hz, 2 H) ppm. 13C NMR (125 MHz, [D6]-
3
was stirred at room temp for 1 h. Finally, hydrazine 3 (1.10 mmol)
followed by methanol (0.5 mL) and glacial acetic acid (0.5 mL)
were added to this suspension, and the reaction mixture was heated
at 150 °C in the microwave cavity for 10 min. After cooling to room
temp., the solvent was removed under reduced pressure, and the
crude products were purified by silica gel flash column chromatog-
raphy (hexane/ethyl acetate) to afford the analytically pure pyr-
azoles 4 (for experimental details, see Table 7).
acetone): δ = 22.2 (CH3), 99.8 (CH), 127.1 (2 CH), 128.7 (2 CH),
130.6 (2 CH), 131.3 (2 CH) ppm. EI MS (70 eV): m/z (%) = 270
(31) [37Cl-M]+, 269 (21) [35Cl13C-M]+, 268 (100) [35Cl-M]+, 267
(14), 201 (15), 199 (16), 183 (10), 149 (13), 119 (12), 77 (22), 57
(15), 51 (12), 43 (16). IR (KBr): ν = 2920 (s), 1638 (m), 1507 (s),
˜
1448 (s), 1385 (w), 1272 (s), 1174 (m), 1098 (s), 1059 (m), 1013 (m),
974 (s), 827 (s), 772 (w), 736 (w) cm–1. UV/Vis (CH2Cl2): λmax (ε) =
262 (20400), 283 (8200 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax
(Stokes shift) = 331 (8000 cm–1) nm.
3-(Thiophen-2-yl)-1H-pyrazole (4a): According to the GP, 4a was
obtained as a yellow oil.[34] 1H NMR (500 MHz, CDCl3): δ = 6.44
3-(4-tert-Butylphenyl)-5-phenyl-1H-pyrazole (4d): According to the
3
3
1
(s, 1 H), 6.94–6.97 (m, 1 H), 7.15 (d, J = 5.0 Hz, 1 H), 7.24 (d, J
= 3.4 Hz, 1 H), 7.52 (s, 1 H), 10.85 (br. s, 1 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 102.6 (CH), 124.1 (CH), 124.5 (CH), 127.5
(CH), 131.4 (Cquat), 135.8 (CH), 145.6 (Cquat) ppm. EI MS (70 eV):
m/z (%) = 150 (100) [M+], 123 (13), 122 (14), 121 (47), 96 (17), 78
GP, 4d was obtained as colorless crystals; m.p. 142 °C. H NMR
(500 MHz, [D6]acetone): δ = 1.34 (s, 9 H), 7.08 (s, 1 H), 7.30–7.35
3
(m, 1 H), 7.40–7.45 (m, 2 H), 7.49 (d, J = 8.6 Hz, 2 H), 7.82 (d,
3J = 8.6 Hz, 2 H), 7.88–7.92 (m, 2 H) ppm. 13C NMR (125 MHz,
[D6]acetone): δ = 32.5 (3 CH3), 36.1 (Cquat), 101.0 (CH), 126.9
(2 CH), 127.1 (2 CH), 127.4 (2 CH), 129.5 (CH), 130.5 (2 CH),
152.5 (Cquat) ppm. EI MS (70 eV): m/z (%) = 277 (11), 276 (55)
[M+], 262 (19), 261 (100), 161 (13), 149 (12), 117 (26), 72 (10), 71
(13), 69 (10), 45 (12), 39 (13). IR (KBr): ν = 2940 (m), 1645 (m),
˜
1559 (w), 1505 (s), 1481 (m), 1418 (s), 1389 (s), 1329 (w), 1299 (w),
1276 (w), 1226 (s), 1048 (s), 942 (m), 914 (m), 847 (s), 759 (s), 705
(s), 644 (w), 612 (w) cm–1. UV/Vis (CH2Cl2): λmax (ε) = 273 (7600),
289 (4500 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax (Stokes shift)
= 330 (6300 cm–1), 363 nm.
(13), 57 (20), 43 (11). IR (KBr): ν = 1588 (w), 1506 (m), 1460 (s),
˜
1363 (s), 1265 (s), 1173 (m), 1118 (m), 1072 (m), 1051 (w), 1026
(w), 967 (s), 909 (w), 834 (s), 797 (s), 764 (s), 739 (s), 689 (s), 650
(m), 552 (m), 515 (m) cm–1. UV/Vis (CH2Cl2): λmax (ε) = 258
(36900), 283 (10700 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax
(Stokes shift) = 323 (7800 cm–1) nm. C19H20N2 (276.4): calcd. C
82.57, H 7.29, N 10.14; found C 82.24, H 7.32, N 10.02.
5-Phenyl-3-(p-tolyl)-1H-pyrazole (4b): According to the GP, 4b was
obtained as colorless crystals; m.p. 167 °C.[13f] 1H NMR (500 MHz,
[D6]DMSO): δ = 2.35 (s, 3 H), 7.25 (d, 2 H), 7.35 (t, 1 H), 7.48 (t,
2 H), 7.73 (d, 2 H), 7.85 (d, 2 H) ppm. 13C NMR (125 MHz, [D6]-
DMSO): δ = 22.4 (CH3), 99.6 (CH), 125.41 (2 CH), 125.46 (2 CH),
128.07 (CH), 129.14 (2 CH), 129.74 (2 CH), 137.51 (Cquat) ppm. EI
MS (70 eV): m/z (%) = 235 (19), 234 (100) [M+], 233 (27), 167 (11),
5-Phenyl-3-[4-(trifluoromethyl)phenyl]-1H-pyrazole (4e): According
to the GP, 4e was obtained as colorless crystals; m.p. 226 °C.[35] 1
H
NMR (500 MHz, [D6]acetone): δ = 2.36 (s, 3 H), 7.26 (s, 1 H),
149 (42). IR (KBr): ν = 2912 (m), 1656 (m), 1509 (s), 1476 (m),
˜
3
7.30–7.40 (m, 1 H), 7.45–7.50 (m, 2 H), 7.78 (d, J = 8.1 Hz, 2 H),
1459 (s), 1269 (m), 1179 (m), 1076 (m), 974 (s), 819 (s), 757 (s), 684
7.87–7.91 (m, 2 H), 8.12 (d, 3J = 8.1 Hz, 2 H), 13.65 (br. s,
([D6]DMSO), 1 H) ppm. 13C NMR (125 MHz, [D6]acetone): δ =
102.2 (CH), 127.2 (CH), 127.5 (q, 3JC–F = 3.8 Hz, CH), 127.6 (CH),
130.8 (CH), 131.3 (CH) ppm. EI MS (70 eV): m/z (%) = 289 (20),
(s), 511 (m) cm–1. UV/Vis (CH2Cl2): λmax (ε)
=
258
(95900 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax (Stokes shift) =
331 (8600 cm–1), 360 nm.
5-(4-Chlorophenyl)-3-(p-tolyl)-1H-pyrazole (4c): According to the
GP, 4c was obtained as colorless crystals; m.p. 209 °C.[5] 1H NMR
288 (100) [M+], 259 (13), 77 (10). IR (KBr): ν = 1619 (w), 1481
˜
(w), 1325 (s), 1167 (m), 1155 (m), 1107 (m), 1067 (m), 1016 (w),
4164
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© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 2008, 4157–4168

Highly Fluorescent 1,3,5-Trisubstituted Pyrazoles
968 (m), 844 (m), 802 (m), 769 (s), 743 (w), 678 (w), 652 (w), 593 1067 (m), 1000 (s), 918 (w), 834 (s), 787 (s), 746 (w), 696 (s), 548
(w), 518 (m) cm–1. UV/Vis (CH2Cl2): λmax (ε)
=
259 (m) cm–1. UV/Vis (CH2Cl2): λmax (ε) =260 (53300), 273
(5300 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax (Stokes shift) =
(54900 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax (Stokes shift) =
362, 379 (10200 cm–1), 404 nm. C15H11BrN2S (319.2): calcd. C
52.68, H 3.47, N 8.78; found C 52.70, H 3.54, N 8.68.
333 (8600 cm–1), 358 nm.
5-Butyl-3-(4-chlorophenyl)-1H-pyrazole (4f): According to the GP,
4f was obtained as colorless crystals; m.p. 65 °C. 1H NMR
10-n-Hexyl-3-[1-methyl-3-(thiophen-2-yl)-1H-pyrazol-5-yl]-10H-phe-
nothiazine (4j): According to the GP, 4j was obtained as a yellow
3
(300 MHz, CDCl3): δ = 0.69 (t, J = 7.3 Hz, 3 H), 1.10 (m, 2 H),
3
3
1
3
1.38 (q, J = 7.5 Hz, 2 H), 2.34 (t, J = 7.5 Hz, 2 H), 6.11 (s, 1 H), resin. H NMR (500 MHz, [D6]acetone): δ = 0.87 (t, J = 6.8 Hz,
3
3
3
7.11 (d, J = 8.5 Hz, 2 H), 7.45 (d, J = 8.5 Hz, 2 H), 11.24 (br. s, 3 H), 1.29–1.35 (m, 4 H), 1.45–1.53 (m, 2 H), 1.84 (q, J = 7.3 Hz,
1 H) ppm. 13C NMR (75 MHz, CDCl3): δ = 13.7 (CH3), 22.3 2 H), 3.88 (s, 3 H), 4.00 (t, 3J = 7.8 Hz, 2 H), 6.63 (s, 1 H), 6.98
3
4
(CH2), 25.9 (CH2), 31.3 (CH2), 100.9 (CH), 127.3 (2 CH), 128.8 (dt, J = 7.5, J = 1.0 Hz, 1 H), 7.06–7.09 (m, 2 H), 7.14–7.25 (m,
(2 CH), 131.5 (Cquat), 133.4 (Cquat), 147.7 (Cquat), 149.4 (Cquat
)
3 H), 7.32 (d, 3J = 2.0 Hz, 1 H), 7.36–7.40 (m, 3 H) ppm. 13C NMR
(125 MHz, [D6]acetone): δ = 14.4 (CH3), 23.4 (CH2), 27.3 (CH2),
ppm. EI MS (70 eV): m/z (%) = 236 (10) [37Cl-M]+, 234 (32) [35Cl-
M]+, 194 (32), 192 (100), 157 (15). IR (KBr): ν = 2963 (s), 1655 27.6 (CH2), 32.3 (CH2), 38.1 (CH3), 48.0 (CH2), 103.3 (CH), 116.6
˜
(w), 1561 (w), 1509 (m), 1459 (w), 1262 (s), 1092 (s), 1030 (s), 801 (CH), 117.0 (CH), 123.8 (CH), 124.2 (CH), 125.0 (Cquat), 125.1
(s), 509 (w) cm–1. UV/Vis (CH2Cl2): λmax (ε)
=
257 (CH), 125.6 (Cquat), 126.0 (Cquat), 128.0 (CH), 128.3 (CH), 128.8
(38100 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax (Stokes shift) =
320 (7700 cm–1) nm. C13H15ClN2 (234.7): calcd. C 66.52, H 6.44,
N 11.93; found C 66.34, H 6.48, N 11.75.
(CH), 130.2 (CH), 132.8 (CH), 138.2 (Cquat), 144.7 (Cquat), 145.9
(Cquat), 146.3 (Cquat), 146.7 (Cquat) ppm. MALDI-TOF MS (ma-
trix: dithranol): m/z = 445 [M]+. IR (KBr): ν = 2921 (s), 2851 (s),
˜
1605 (m), 1579 (m), 1460 (s), 1458 (s), 1398 (m), 1376 (m), 1331
(m), 1284 (s), 1244 (s), 1133 (m), 1072 (w), 1039 (w), 920 (s), 887
(m), 847 (m), 822 (m), 785 (s), 748 (s), 694 (s) cm–1. UV/Vis
(CH2Cl2): λmax (ε) = 269 (97200), 320 (18600 Lmol–1 cm–1) nm.
Emission (CH2Cl2): λmax (Stokes shift) = 356, 452 (9100 cm–1),
504 nm. C26H27N3S2 (445.6): calcd. C 70.07, H 6.11, N 9.43; found
C 69.74, H 6.17, N 9.23.
1-Methyl-3-(thiophen-2-yl)-1H-pyrazole (4g): According to the GP,
4g was obtained as a yellow oil.[36] 1H NMR (500 MHz, CDCl3):
3
δ = 3.98 (s, 3 H), 6.39 (d, 3J = 1.3 Hz, 1 H), 7.12 (t, J = 4.4 Hz,
1 H), 7.16 (d, 3J = 3.5 Hz, 1 H), 7.40 (d, 3J = 5.1 Hz, 1 H), 7.48 (d,
3J = 1.3 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 33.8
(CH3), 106.7 (CH), 126.5 (CH), 126.8 (CH), 127.6 (CH), 131.3
(Cquat), 136.5 (Cquat), 138.4 (CH) ppm. EI MS (70 eV): m/z (%) =
165 (12), 164 (100) [M+], 163 (21), 42 (15). IR (KBr): ν = 3104 (m), 3-(4-Methoxyphenyl)-1-methyl-5-phenyl-1H-pyrazole (4k): Accord-
˜
2943 (m), 1647 (w), 1469 (m), 1416 (m), 1389 (s), 1275 (s), 1209 (s), ing to the GP, 4k was obtained as colorless crystals; m.p. 73 °C.[7f]
1060 (m), 1020 (m), 941 (s), 920 (w), 848 (s), 778 (s), 702 (s), 646
1H NMR (500 MHz, CDCl3): δ = 3.74 (s, 3 H), 3.81 (s, 3 H), 6.44
3
3
(s), 512 (w) cm–1. UV/Vis (CH2Cl2): λmax (ε) = 247 (10800), 273 (s, 1 H), 6.85 (d, J = 8.9 Hz, 2 H), 7.30–7.37 (m, 5 H), 7.67 (d, J
(13500 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax (Stokes shift) =
= 8.9 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 37.4 (CH3),
55.2 (CH3), 102.7 (CH), 114.0 (2 CH), 126.2 (Cquat), 126.7 (2 CH),
128.4 (CH), 128.6 (2 CH), 128.7 (2 CH), 130.0 (Cquat), 144.0
(Cquat), 150.3 (Cquat), 159.2 (Cquat) ppm. EI MS (70 eV): m/z (%) =
265 (18), 264 (100) [M]+, 249 (46), 221 (19), 152 (20), 116 (30), 115
348 (7900 cm–1) nm.
1-Methyl-5-(4-nitrophenyl)-3-(thiophen-2-yl)-1H-pyrazole (4h): Ac-
cording to the GP, 4h was obtained as yellow solid; m.p. 76 °C. 1H
NMR (500 MHz, CDCl3): δ = 3.85 (s, 3 H), 6.53 (s, 1 H), 6.97–
(32), 89 (10), 77 (15), 73 (13), 43 (13). IR (KBr): ν = 3050 (s), 3017
˜
3
4
7.00 (m, 1 H), 7.18 (dd, J = 4.9 Hz, J = 1.0 Hz, 1 H), 7.26 (dd,
3J = 4.9 Hz, 4J = 1.0 Hz, 1 H), 7.55 (dd, 3J = 8.6 Hz, 2 H), 8.24 (d,
3J = 8.6 Hz, 2 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 37.8
(CH3), 104.1 (CH), 123.7 (CH), 124.0 (2 CH), 124.7 (CH), 127.5
(CH), 129.3 (2 CH), 135.8 (Cquat), 136.4 (Cquat), 142.7 (Cquat), 146.1
(Cquat), 147.5 (Cquat) ppm. EI MS (70 eV): m/z (%) = 182 (21), 167
(s), 2937 (s), 2839 (s), 1682 (w), 1646 (w), 1608 (s), 1578 (s), 1522
(s), 1486 (s), 1358 (s), 1291 (s), 1245 (m), 1176 (s), 1111 (s), 1025
(s), 958 (s), 919 (s), 829 (s), 792 (s), 765 (s), 967 (s), 670 (s), 602 (s),
566 (s), 525 (s) cm–1. UV/Vis (CH2Cl2): λmax (ε)
= 260
(52400 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax (Stokes shift) =
347, 369 (11400 cm–1) nm.
(17), 111 (100), 39 (16). IR (KBr): ν = 2951 (m), 1651 (w), 1600
˜
(w), 1520 (m), 1466 (s), 1341 (s), 1282 (m), 1126 (m), 1073 (w),
3-(4-Chlorophenyl)-1-methyl-5-phenyl-1H-pyrazole (4l): According
1050 (w), 854 (m), 741 (m), 714 (m) cm–1. UV/Vis (CH2Cl2): λmax to the GP, 4l was obtained as colorless crystals; m.p. 95 °C.[19] 1
H
(ε) = 286 (58800), 297 (20400), 334 (9200 Lmol–1 cm–1) nm. Emis-
sion (CH2Cl2): λmax (Stokes shift) = 357 (7000 cm–1), 518 nm.
C14H11N3O2S (285.3): calcd. C 58.93, H 3.89, N 14.73; found C
58.84, H 3.99, N 14.53.
NMR (500 MHz, CDCl3): δ = 3.93 (s, 3 H), 6.58 (s, 1 H), 7.38 (d,
3J = 8.5 Hz, 2 H), 7.43–7.51 (m, 5 H), 7.77 (d, 3J = 8.5 Hz, 2 H)
ppm. 13C NMR (125 MHz, CDCl3): δ = 37.6 (CH3), 103.1 (CH),
126.7 (2 CH), 128.6 (CH), 128.68 (2 CH), 128.71 (2 CH), 128.75
(2 CH), 130.4 (Cquat), 131.9 (Cquat), 133.2 (Cquat), 145.2 (Cquat),
149.3 (Cquat) ppm. EI MS (70 eV): m/z (%) = 271 (7)[37Cl13C-M]+,
270 (35) [37Cl-M]+, 269 (23)[35Cl13C-M]+, 268 (100)[35Cl-M]+, 267
(13), 234 (35), 233 (19), 219 (21), 218 (11), 118 (11), 117 (12), 89
5-(4-Bromophenyl)-1-methyl-3-(thiophen-2-yl)-1H-pyrazole (4i): Ac-
1
cording to the GP, 4i was obtained as yellow solid; m.p. 65 °C. H
NMR (500 MHz, CDCl3): δ = 3.78 (s, 3 H), 6.41 (s, 1 H), 6.96 (dd,
3
3
3
3J = 4.9, J = 3.6 Hz, 1 H), 6.96 (dd, J = 4.9, J = 0.9 Hz, 1 H),
7.19–7.25 (m, 3 H), 7.50 (d, 3J = 8.4 Hz, 2 H) ppm. 13C NMR
(125 MHz, CDCl3): δ = 37.4 (CH3), 103.2 (CH), 123.0 (Cquat),
123.5 (CH), 124.4 (CH), 127.4 (CH), 129.1 (Cquat), 130.2 (2 CH),
131.9 (2 CH), 136.2 (Cquat), 143.8 (Cquat), 145.8 (Cquat) ppm. EI
MS (70 eV): m/z (%) 321 (9) [81Br13C-M]+, 320 (51) [81Br-M]+, 319
(13)[79Br13C-M]+, 318 (47) [79Br-M]+, 240 (12), 217 (12), 168 (13),
161 (30), 121 (11), 117 (55), 111 (56), 90 (11), 89 (12), 85 (16), 83
(10), 71 (26), 57 (100), 55 (14), 43 (25), 41 (25), 39 (17). IR (KBr):
(11), 77 (13), 71 (14), 57 (16), 55 (10), 43 (13). IR (KBr): ν = 2948
˜
(s), 1605 (w), 1511 (w), 1484 (s), 1436 (s), 1363 (w), 1283 (m), 1235
(m), 1192 (m), 1087 (s), 1037 (w), 1011 (s), 958 (s), 836 (s), 797 (s),
770 (s), 754 (s), 701 (s), 673 (m), 566 (s), 511 (s) cm–1. UV/Vis
(CH2Cl2): λmax (ε) = 260 (87500), 280 (35200 Lmol–1 cm–1) nm.
Emission (CH2Cl2): λmax (Stokes shift) = 331 (8400 cm–1) nm.
3-(4-Chlorophenyl)-1-methyl-5-propyl-1H-pyrazole (4m): According
to the GP, 4m was obtained as colorless crystals; m.p. 54 °C. 1H
3
ν = 2929 (m), 1655 (w), 1638 (w), 1597 (w), 1560 (w), 1479 (s),
NMR (500 MHz, CDCl3): δ = 1.02 (t, J = 7.3 Hz, 3 H), 1.70 (s,
˜
3
1443 (m), 1390 (s), 1325 (w), 1284 (s), 1221 (w), 1167 (w), 1105 (w),
3J = 7.5 Hz, 2 H), 2.57 (t, J = 7.6 Hz, 2 H), 3.81 (s, 3 H), 6.29 (s,
Eur. J. Org. Chem. 2008, 4157–4168
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4165

B. Willy, T. J. J. Müller
FULL PAPER
1 H), 7.33 (d, 3J = 8.4 Hz, 2 H), 7.69 (d, 3J = 8.4 Hz, 2 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 13.8 (CH3), 21.7 (CH2), 27.6
(CH2), 36.1 (CH3), 101.5 (CH), 126.6 (2 CH), 128.6 (2 CH), 132.2
(Cquat), 132.9 (Cquat), 144.6 (Cquat), 148.8 (Cquat) ppm. EI MS
Methyl 4-[1-(4-Bromophenyl)-5-(thiophen-2-yl)-1H-pyrazol-3-yl]-
benzoate (4q): According to the GP, 4q was obtained as light yellow
crystals; m.p. 123 °C. 1H NMR (500 MHz, CDCl3): δ = 3.82 (s,
3
3
3 H), 6.78 (dd, J = 3.6, J = 1.1 Hz, 1 H), 6.80 (s, 1 H), 6.88 (dd,
(70 eV): m/z (%) = 237 (3) [37Cl13C-M]+, 236 (27) [37Cl-M]+, 235 3J = 5.1, 3J = 3.6 Hz, 1 H), 7.21–7.24 (sh, 3 H), 7.44 (d, 3J = 8.7 Hz,
(10) [35Cl13C-M]+, 234 (70) [35Cl-M]+, 208 (28), 207 (41), 206 (84),
2 H), 7.85 (d, 3J = 8.5 Hz, 2 H), 7.98 (d, 3J = 8.5 Hz, 2 H) ppm.
205 (100), 218 (11), 127 (16). IR (KBr): ν = 2958 (m), 1662 (m), 13C NMR (125 MHz, CDCl3): δ = 52.0 (CH3), 105.9 (CH), 122.1
˜
1599 (s), 1521 (s), 1461 (m), 1346 (s), 1109 (m), 1048 (m), 1011 (m), (Cquat), 125.5 (2 CH), 127.0 (CH), 127.3 (2 CH), 127.5 (CH), 127.7
855 (s), 765 (s), 713 (m), 696 (w) cm–1. UV/Vis (CH2Cl2): λmax (ε) (CH), 129.5 (Cquat), 130.0 (2 CH), 130.4 (Cquat), 132.1 (2 CH),
= 262 (106400 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax (Stokes
shift) = 323 (7200 cm–1) nm. C13H15ClN2 (234.7): calcd. C 66.52,
H 6.44, N 11.93; found C 66.37, H 4.47, N 11.79.
136.8 (Cquat), 138.3 (Cquat), 138.5 (Cquat), 151.0 (Cquat), 166.8
(Cquat) ppm. EI MS (70 eV): m/z (%) = 441 (29), 440 (100) [81Br-
M]+, 439 (35), 438 (92) [79Br-M]+, 437 (11), 409 (13), 407 (12), 318
(21), 294 (46), 287 (17), 264 (10), 263 (40), 164 (11), 150 (11), 111
4-[5-(4-Methoxyphenyl)-1-methyl-1H-pyrazol-3-yl]benzonitrile (4n):
According to the GP, 4n was obtained as light yellow solid; m.p.
143 °C. 1H NMR (500 MHz, CDCl3): δ = 3.87 (s, 3 H), 3.92 (s,
(66), 43 (33), 39 (11). IR (KBr): ν = 3108 (w), 2956 (w), 1714 (s),
˜
1612 (m), 1587 (w), 1492 (s), 1438 (m), 1408 (w), 1354 (w), 1310
(m), 1282 (s), 1197 (w), 1176 (m), 1107 (m), 1070 (m), 1012 (m),
957 (m), 926 (w), 861 (w), 849 (w), 829 (s), 773 (s), 706 (s), 595 (w),
535 (w), 519 (w) cm–1. UV/Vis (CH2Cl2): λmax (ε) = 287 (44200),
348 (1300 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax (Stokes shift)
= 383 (8700 cm–1) nm. C21H15BrN2O2S (439.3): calcd. C 57.41, H
3.44, N 6.38; found C 57.39, H 3.49, N 6.32.
3
3
3 H), 6.60 (s, 1 H), 7.01 (d, J = 8.2 Hz, 2 H), 7.38 (d, J = 8.2 Hz,
2 H), 7.68 (d, 3J = 8.0 Hz, 2 H), 7.92 (d, 3J = 8.0 Hz, 2 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 37.7 (CH3), 55.4 (CH3), 103.5
(CH), 110.7 (Cquat), 114.2 (2 CH), 119.1 (Cquat), 122.4 (Cquat), 125.7
(2 CH), 130.0 (2 CH), 132.5 (2 CH), 137.9 (Cquat), 145.4 (Cquat),
148.3 (Cquat), 160.0 (Cquat) ppm. EI MS (70 eV): m/z (%) = 290
(21), 289 (100) [M]+, 274 (29), 45 (10). IR (KBr): ν = 2958 (w),
1-(4-Chlorophenyl)-3-[4-(pyrrolidin-1-yl)phenyl]-5-(thiophen-2-yl)-
˜
2837 (w), 2224 (s), 1611 (m), 1560 (w), 1494 (s), 1447 (w), 1424 (w),
1363 (w), 1296 (m), 1278 (w), 1259 (s), 1176 (s), 1115 (w), 1039
1H-pyrazole (4r): According to the GP, 4r was obtained as a yellow
3
resin. 1H NMR (500 MHz, CDCl3): δ = 2.02 (d, J = 6.6 Hz, 4 H),
3
3
(m), 1019 (w), 1001 (w), 958 (w), 841 (s), 826 (m), 788 (m), 611 3.29 (t, J = 6.6 Hz, 4 H), 6.49 (d, J = 8.8 Hz, 2 H), 6.61 (s, 1 H),
(m), 552 (m), 513 (w) cm–1. UV/Vis (CH2Cl2): λmax (ε) = 280 7.07–7.11 (sh, 3 H), 7.26–7.41 (sh, 8 H) ppm. 13C NMR (125 MHz,
(49100 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax (Stokes shift) =
CDCl3): δ = 22.4 (2 CH2), 47.5 (2 CH2), 104.2 (CH), 111.3 (2 CH),
116.3 (Cquat), 124.0 (CH), 124.7 (CH), 126.4 (2 CH), 127.4 (CH),
128.9 (2 CH), 129.6 (2 CH),132.6 (Cquat), 136.4 (Cquat), 138.9
(Cquat), 145.3 (Cquat), 147.4 (Cquat), 147.7 (Cquat) ppm. EI MS
(70 eV): m/z (%) = 408 (10), 407 (40) [37Cl-M]+, 406 (35), 405 (100)
[35Cl-M]+, 404 (26), 167 (10), 149 (15), 57 (16), 43 (17). IR (KBr):
392 (10200 cm–1) nm.
4-[3-(4-Methoxyphenyl)-1-methyl-1H-pyrazol-5-yl]benzonitrile (4o):
According to the GP, 4o was obtained as light yellow solid; m.p.
120 °C. 1H NMR (500 MHz, CDCl3): δ = 3.88 (s, 3 H), 3.92 (s,
3
3
3 H), 6.60 (s, 1 H), 7.01 (d, J = 8.2 Hz, 2 H), 7.38 (d, J = 8.2 Hz,
2 H), 7.68 (d, 3J = 8.0 Hz, 2 H), 7.92 (d, 3J = 8.0 Hz, 2 H) ppm.
13C NMR (125 MHz, CDCl3): δ = 37.7 (CH3), 55.4 (CH3), 103.5
(CH), 110.7 (Cquat), 114.2 (2 CH), 119.1 (Cquat), 122.4 (Cquat), 125.8
(2 CH), 130.0 (2 CH), 132.5 (2 CH), 137.9 (Cquat), 145.4 (Cquat),
148.4 (Cquat), 160.0 (Cquat) ppm. EI MS (70 eV): m/z (%) = 290
ν = 2925 (m), 2852 (s), 1612 (s), 1543 (w), 1496 (s), 1440 (w), 1375
˜
(s), 1228 (w), 1184 (m), 1090 (m), 1013 (w), 971 (w), 917 (w), 832
(s), 791 (m), 702 (m) cm–1. UV/Vis (CH2Cl2): λmax (ε) = 295
(98500), 385 (19100 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax
(Stokes shift) = 460 (4200 cm–1) nm. C23H20ClN3S (405.9): calcd.
C 68.05, H 4.97, N 10.35; found C 67.81, H 5.04, N 10.17.
(22), 289 (100) [M]+, 274 (29). IR (KBr): ν = 2925 (w), 2226 (s),
˜
1647 (m), 1611 (s), 1492 (s), 1467 (w), 1449 (w), 1424 (w), 1360 (w),
5-(4-Chlorophenyl)-1,3-diphenyl-1H-pyrazole (4s): According to the
1296 (m), 1254 (s), 1176 (s), 1112 (w), 1030 (m), 1001 (w), 958 (w), GP, 4s was obtained as colorless crystals; m.p. 69 °C.[19] 1H NMR
3
847 (s), 828 (s), 769 (s), 712 (w), 676 (w), 613 (m), 568 (m), 548
(500 MHz, CDCl3): δ = 6.80 (s, 1 H), 7.18 (dd, J = 8.5 Hz, 2 H),
(m), 510 (w) cm–1. UV/Vis (CH2Cl2): λmax (ε)
=
278 7.22–7.44 (m, 10 H), 7.91 (d, 3J = 8.5 Hz, 2 H) ppm. 13C NMR
(48600 Lmol–1 cm–1) nm. Emission (CH2Cl2): λmax (Stokes shift) =
(125 MHz, CDCl3): δ = 105.2 (CH), 125.2 (2 CH), 125.7 (2 CH),
127.6 (CH), 128.4 (CH), 128.6 (2 CH), 128.7 (2 CH), 128.9 (Cquat),
129.0 (2 CH), 129.9 (2 CH), 132.8 (Cquat), 134.3 (Cquat), 139.8
(Cquat), 143.1 (Cquat), 152.0 (Cquat) ppm. EI MS (70 eV): m/z (%) =
332 (37) [37Cl-M]+, 331 (32) [35Cl13C-M]+, 330 (100) [35Cl-M]+, 329
(41), 165 (13), 139 (24), 111 (11), 105 (15), 77 (39), 75 (11), 51 (13).
392 (10500 cm–1) nm.
4-[3-(2,4-Dichlorophenyl)-1-methyl-1H-pyrazol-5-yl]benzonitrile
(4p): According to the GP, 4p was obtained as colorless crystals;
1
m.p. 164 °C. H NMR (500 MHz, CDCl3): δ = 3.98 (s, 3 H), 6.92
4
4
(s, 1 H), 7.31 (dd, 3J = 8.4, J = 2.1 Hz, 1 H), 7.48 (d, J = 2.1 Hz,
1 H), 7.61 (d, 3J = 8.5 Hz, 1 H), 7.79 (d, 3J = 8.5 Hz, 2 H), 7.81 (d,
3J = 8.4 Hz, 1 H) ppm. 13C NMR (125 MHz, CDCl3): δ = 38.0
(CH3), 108.0 (CH), 112.4 (Cquat), 118.3 (Cquat), 127.3 (CH), 128.4
(Cquat), 129.3 (2 CH), 130.1 (CH), 130.4 (Cquat), 131.1 (CH), 132.6
IR (KBr): ν = 2926 (w), 1597 (m), 1499 (s), 1458 (s), 1360 (m),
˜
1275 (m), 1212 (w), 1176 (w), 1092 (s), 1014 (m), 971 (m), 912 (w),
834 (m), 801 (m), 765 (s), 693 (s), 597 (m), 536 (w) cm–1. UV/
Vis (CH2Cl2): λmax (ε) = 259 (50700), 293 (17400 Lmol–1 cm–1) nm.
Emission (CH2Cl2): λmax (Stokes shift) = 382 (12300 cm–1) nm.
(2 CH), 134.1 (Cquat), 134.7 (Cquat), 142.4 (Cquat), 147.4 (Cquat
)
ppm. EI MS (70 eV): m/z (%) = 331 (11) [37Cl,37Cl -M]+, 330 (15) 3-Butyl-5-(4-chlorophenyl)-1-phenyl-1H-pyrazole (4t): According to
[37Cl,35Cl,13C-M]+, 329 (74) [37Cl,35Cl-M]+, 328 (32) [35Cl,35Cl,13C - the GP, 5t was obtained as a yellow oil. 1H NMR (300 MHz,
M]+, 327 (100) [35Cl,35Cl -M]+, 326 (13), 143 (19), 128 (13), 102 CDCl3): δ = 0.98 (t, J = 7.3 Hz, 3 H), 1.47 (m, 2 H), 1.74 (q, J =
3
3
3
3
(15). IR (KBr): ν = 3056 (w), 2360 (w), 2233 (s), 1612 (s), 1555 (w),
7.6 Hz, 2 H), 2.74 (t, J = 7.6 Hz, 2 H), 6.33 (s, 1 H), 7.15 (d, J =
˜
3
1482 (s), 1434 (s), 1376 (w), 1343 (w), 1277 (w), 1249 (w), 1190 (m),
8.6 Hz, 2 H), 7.26 (d, J = 8.6 Hz, 2 H), 7.26–7.37 (m, 5 H) ppm.
1103 (m), 1055 (m), 1034 (m), 1007 (m), 959 (m), 847 (s), 834 (s), 13C NMR (75 MHz, CDCl3): δ = 13.9 (CH3), 22.6 (CH2), 28.0
797 (s), 719 (w), 690 (w), 572 (w), 555 (m), 516 (w) cm–1. UV/
Vis (CH2Cl2): λmax (ε) = 269 (24600 Lmol–1 cm–1) nm. Emission (CH), 128.9 (CH), 129.4 (Cquat), 129.8 (CH), 134.0 (Cquat), 140.0
(CH2Cl2): λmax (Stokes shift) = 383 (11100 cm–1) nm.
(Cquat), 142.2 (Cquat), 154.4 (Cquat) ppm. EI MS (70 eV): m/z (%) =
(CH2), 31.8 (CH2), 106.8 (CH), 125.2 (CH), 127.2 (CH), 128.6
4166
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Eur. J. Org. Chem. 2008, 4157–4168

Highly Fluorescent 1,3,5-Trisubstituted Pyrazoles
312 (3) [37Cl-M]+, 310 (10) [35Cl-M]+, 281 (14), 270 (38), 268 (100).
IR (KBr): ν = 2957 (m), 2941 (m), 2871 (m), 1599 (s), 1545 (w),
˜
[1] For general reviews, see, for example: a) A. N. Kost, I. I.
Grandberg, Adv. Heterocycl. Chem. 1966, 6, 347–429; b) J. El-
guero in Comprehensive Heterocyclic Chemistry (Eds.: A. R.
Katritzky, C. W. Rees), Pergamon, Oxford, 1984, vol. 5, p. 167;
c) J. Elguero in Comprehensive Heterocyclic Chemistry II (Eds.:
A. R. Katritzky, C. W. Rees, E. F. V. Scriven), Elsevier, Oxford,
1996, vol. 3, p. 1.
1504 (s), 1438 (m), 1400 (w), 1374 (m), 1192 (w), 1141 (w), 1092
(s), 1015 (s), 969 (s), 910 (w), 834 (s), 797 (m), 760 (s), 694 (s), 582
(m) cm–1. UV/Vis (CH2Cl2): λmax (ε) = 263 (10500 Lmol–1 cm–1)
nm. Emission (CH2Cl2): λmax (Stokes shift) = 339 (8500 cm–1) nm.
C19H19ClN2 (310.8): calcd. C 73.42, H 6.16, N 9.01; found C 73.11,
H 6.21, N 8.86.
[2]
D. J. Wustrow, T. Capiris, R. Rubin, J. A. Knobelsdorf, H.
Akunne, M. D. Davis, R. MacKenzie, T. A. Pugsley, K. T. Zo-
ski, T. G. Heffner, L. D. Wise, Bioorg. Med. Chem. Lett. 1998,
8, 2067–2070.
1-(4-Bromophenyl)-3-butyl-5-(4-chlorophenyl)-1H-pyrazole (4u): Ac-
cording to the GP, 4u was obtained as colorless crystals; m.p. 83 °C.
3
1H NMR (500 MHz, CDCl3): δ = 0.90 (t, J = 7.5 Hz, 3 H), 1.36
[3]
[4]
G. Menozzi, L. Mosti, P. Fossa, F. Mattioli, M. Ghia, J. Heter-
ocycl. Chem. 1997, 34, 963–968.
(sext, 3J = 7.5 Hz, 2 H), 1.62 (q, 3J = 7.6 Hz, 2 H), 2.65 (t, 3J =
7.7 Hz, 2 H), 6.51 (s, 1 H), 7.34–7.38 (m, 4 H), 7.61 (d, 3J = 8.6 Hz,
2 H), 7.78 (d, 3J = 8.5 Hz, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 13.7 (CH3), 22.3 (CH2), 26.0 (CH2), 30.8 (CH2), 103.1
(CH), 121.6 (Cquat), 126.8 (2 CH), 126.9 (2 CH), 128.7 (2 CH),
131.6 (Cquat), 132.2 (2 CH), 133.5 (Cquat), 138.8 (Cquat), 145.6
(Cquat), 150.6 (Cquat) ppm. EI MS (70 eV): m/z (%) = 390 (18)
[81Br35Cl-M, 79Br37Cl-M]+, 388 (11) [79Br35Cl-M]+, 348 (32), 347
(10), 346 (25), 268 (12), 258 (13), 256 (18), 229 (20), 227 (27), 221
(19), 213 (10), 179 (16), 149 (18), 145 (12), 141 (32), 139 (100), 129
(12), 117 (20), 115 (23), 113 (17), 111 (46), 89 (13), 77 (20), 76 (14),
T. D. Penning, J. J. Talley, S. R. Bertenshaw, J. S. Carter, P. W.
Collins, S. Docter, M. J. Graneto, L. F. Lee, J. W. Malecha,
J. M. Miyashiro, R. S. Rogers, D. J. Rogier, S. S. Yu, G. D. An-
derson, E. G. Burton, J. N. Cogburn, S. A. Gregory, C. M. Ko-
boldt, W. E. Perkins, K. Seibert, A. W. Veenhuizen, Y. Y.
Zhang, P. C. Isakson, J. Med. Chem. 1997, 40, 1347–1365.
F. Chimenti, R. Fioravanti, A. Bolasco, F. Manna, P. Chimenti,
D. Secci, O. Befani, P. Turini, F. Ortuso, S. Alcaro, J. Med.
Chem. 2007, 50, 425–428.
[5]
[6]
[7]
B. Walworth, E. Klingsberg, German Patent, 1973,
DE 2260485 19730628, 1–60.
75 (26), 57 (26), 51 (11), 43 (15), 41 (18). IR (KBr): ν = 2959 (s),
˜
For representative reviews, see, for example: a) S. Trofimenko,
Chem. Rev. 1972, 72, 497–509; b) R. Mukherjee, Coord. Chem.
Rev. 2000, 203, 151–218; c) S. Trofimenko, Polyhedron 2004, 23,
197–203; d) M. D. Ward, J. A. McCleverty, J. C. Jeffery, Coord.
Chem. Rev. 2001, 222, 251–272; For recent examples, see, for
example ; e) S. Bieller, A. Haghiri, M. Bolte, J. W. Bats, M.
Wagner, H.-W. Lerner, Inorg. Chim. Acta 2006, 359, 1559–1572;
f) Y. Sun, A. Hienzsch, J. Grasser, E. Herdtweck, W. R. Thiel,
J. Organomet. Chem. 2006, 691, 291–298.
2871 (s), 1655 (w), 1589 (w), 1492 (s), 1449 (m), 1361 (w), 1273
(m), 1091 (s), 1064 (s), 1007 (s), 956 (m), 832 (s), 776 (m), 586 (w),
513 (m) cm–1. UV/Vis (CH2Cl2): λmax (ε) = 275 (34600 Lmol–1
cm–1) nm. Emission (CH2Cl2): λmax (Stokes shift) = 327, 341
(7000 cm–1), 358, 380 nm. C19H18BrClN2 (389.7): calcd. C 58.56,
H 4.66, N 7.19; found C 58.52, H 4.70, N 7.12.
1-Methyl-5-(4Ј-methylbiphenyl-4-yl)-3-(thiophen-2-yl)-1H-pyrazole
(6): According to the GP after the generation of 4i, boronic acid 5
(164 mg, 1.20 mmol), PPh3 (53 mg, 0.20 mmol), K2CO3 (415 mg,
3.00 mmol), and water (1 mL) were added to the reaction mixture.
This mixture was was heated at 150 °C in the microwave cavity for
20 min. After cooling to room temp, the solvent was removed un-
der reduced pressure, and the crude product was purified by flash
column chromatography on silica gel (hexane/ethyl acetate) to af-
ford analytically pure pyrazole 6 as colorless crystals; m.p. 119 °C.
1H NMR (500 MHz, CDCl3): δ = 2.33 (s, 3 H), 3.85 (s, 3 H), 6.46
[8]
[9]
a) A.-F. A. Harb, H. H. Abbas, F. H. Mostafa, Chem. Pap.
2005, 59, 187–195; b) A.-F. A. Harb, H. H. Abbas, F. H. Mos-
tafa, J. Iranian Chem. Soc. 2005, 2, 115–123.
For pyrazoles as optical brightening agents, see, for example:
a) A. K. Sarkar, British Patent 1966, GB 1052179 19661221; b)
C. Eckhardt, H. Hefti, H. R. Meyer, K. Weber, Eur. Pat. Appl.
1989, EP 317979 A2 19890531; c) X. Wang, W. Li, X.-H.
Zhang, D.-Z. Liu, X.-Q. Zhou, Dyes Pigm. 2005, 64, 141–146;
d) V. R. Kanetkar, G. Shankarling, J. Malanker, Colourage
1998, 45, 35–42; e) S. N. Naik, S. S. Puro, Colourage 1995, 42,
56–58; f) Y. M. Udachin, L. V. Chursinova, N. M. Przheval’s-
kii, I. I. Grandberg, G. P. Tokmakov, Izv. Timiryazev. S-kh.
Akad. 1980, 3, 162–169; g) E. Hemingway, Rep. Prog. Appl.
Chem. 1969, 54, 150–158; for a review on heterocycles as active
ingredients in optical brighteners, see, for example: h) A. Dol-
ars, C.-W. Schellhammer, J. Schroeder, Angew. Chem. 1975, 87,
693–707; Angew. Chem. Int. Ed. Engl. 1975, 14, 665–679.
J. Catalan, F. Fabero, R. M. Claramunt, M. D. Santa Maria,
M. C. Foces-Foces, F. Hernandez Cano, M. Martinez-Ripoll,
J. Elguero, R. Sastre, J. Am. Chem. Soc. 1992, 114, 5039–5048.
a) T. Karatsu, N. Shiochi, T. Aono, N. Miyagawa, A. Kita-
mura, Bull. Chem. Soc. Jpn. 2003, 76, 1227–1231; b) Y.-P. Yen,
T.-M. Huang, Y.-P. Tseng, H.-Y. Lin, C.-C. Lai, J. Chin. Chem.
Soc. 2004, 51, 393–398.
3
3
3
(s, 1 H), 6.98 (dd, J = 4.9, J = 3.6 Hz, 1 H), 7.16 (dd, J = 3.6,
4J = 1.0 Hz, 1 H), 7.20 (d, J = 7.6 Hz, 2 H), 7.26 (dd, J = 4.9, J
= 1.0 Hz, 1 H), 7.41 (d, 3J = 8.1 Hz, 2 H), 7.45 (d, 3J = 7.9 Hz,
2 H), 7.59 (d, 3J = 8.1 Hz, 2 H) ppm. 13C NMR (125 MHz,
CDCl3): δ = 21.1 (CH3), 37.6 (CH3), 103.1 (CH), 123.4 (CH), 124.3
(CH), 126.9 (2 CH), 127.1 (2 CH), 127.4 (CH), 128.8 (Cquat), 129.0
(2 CH), 129.6 (2 CH), 136.6 (Cquat), 137.3 (Cquat), 137.6 (Cquat),
141.4 (Cquat), 144.8 (Cquat), 145.8 (Cquat) ppm. EI MS (70 eV): m/z
3
3
4
[10]
[11]
(%) = 331 (24), 330 (100) [M]+, 164 (15). IR (KBr): ν = 1655 (m),
˜
1561 (w), 1514 (w), 1490 (s), 1440 (m), 1399 (m), 1285 (m), 1221
(m), 1181 (m), 1106 (w), 1048 (w), 1005 (m), 919 (m), 852 (s), 844
(m), 815 (s), 797 (s), 741 (w), 696 (s), 644 (w), 573 (m), 534 (m)
cm–1. UV/Vis (CH2Cl2): λmax (ε) = 285 (7600 L mol–1 cm–1
nm. Emission (CH2Cl2): λmax (Stokes shift) = 382 (8900 cm–1
nm.
)
)
[12]
[13]
a) A. Sachse, L. Penkova, G. Noel, S. Dechert, O. A. Varzatskii,
I. O. Fritsky, F. Meyer, Synthesis 2008, 800–806; b) H. Maeda,
Y. Ito, Y. Kusunose, T. Nakanishi, Chem. Commun. 2007,
1136–1138; c) S. Gemming, M. Schreiber, W. Thiel, T. Heine,
G. Seifert, H. Avelino de Abreu, H. Anderson Duarte, J. Lu-
min. 2004, 109, 143–147.
For recent pyrazole syntheses, see, for example: a) T. T. Dang,
T. T. Dang, C. Fischer, H. Görls, P. Langer, Tetrahedron 2008,
64, 2207–2215; b) H.-L. Liu, H.-F. Jiang, M. Zhang, W.-J. Yao,
Q.-H. Zhu, Z. Tang, Tetrahedron Lett. 2008, 49, 3805–3809; c)
K. Wang, D. Xiang, J. Liu, W. Pan, D. Dong, Org. Lett. 2008,
10, 1691–1694; d) M. C. Bagley, M. C. Lubinu, C. Mason, Syn-
Acknowledgments
Financial support from the Fonds der Chemischen Industrie is
gratefully acknowledged. The authors also cordially thank CEM
for a research cooperation and BASF AG and Clariant AG for the
generous donation of chemicals.
Eur. J. Org. Chem. 2008, 4157–4168
© 2008 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
4167

B. Willy, T. J. J. Müller
FULL PAPER
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Received: May 6, 2008
Published Online: July 10, 2008
4168
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