Polykis(pyrazol-1-yl)benzenes: preparation, structure, and complexation with copper and palladium

Article abstract of DOI:10.1016/j.tet.2009.04.035

A series of polykis(pyrazol-1-yl)benzenes, potential chelating ligands for transition metals, have been prepared by nucleophilic substitution of fluorine in 1,2-difluoro-, 1,2,3,4-tetrafluoro-, 1,2,4,5-tetrafluoro-, and hexafluorobenzenes. The observed su

Full text of DOI:10.1016/j.tet.2009.04.035

Tetrahedron 65 (2009) 4652–4658
Contents lists available at ScienceDirect
Tetrahedron
journal homepage: www.elsevier.com/locate/tet
Polykis(pyrazol-1-yl)benzenes: preparation, structure, and complexation
with copper and palladium
*
Olga Ivashchuk, Vladimir I. Sorokin
Department of Organic Chemistry, Southern Federal University, Zorge Street 7, Rostov-on-Don 344090, Russia
a r t i c l e i n f o
a b s t r a c t
Article history:
A series of polykis(pyrazol-1-yl)benzenes, potential chelating ligands for transition metals, have been
prepared by nucleophilic substitution of fluorine in 1,2-difluoro-, 1,2,3,4-tetrafluoro-, 1,2,4,5-tetrafluoro-,
and hexafluorobenzenes. The observed substitution pattern indicated formation of early TS, making
activation by fluorines ortho- to the site of nucleophilic attack dominant. Complexation of the synthe-
sized ligands with copper(II) and palladium(II) was analyzed by ESI mass spectrometry. X-ray structures
were determined for palladium(II) complex with 1,2-bis(pyrazol-1-yl)benzene and copper(II) complex
with 1,4-difluoro-2,3-bis(pyrazol-1-yl)benzene, revealing an unusual seven-membered chelate cycle
formation.
Received 3 February 2009
Received in revised form 22 March 2009
Accepted 9 April 2009
Available online 17 April 2009
Keywords:
Polykis(pyrazol-1-yl)benzenes
Polyfluorobenzenes
Nucleophilic substitution
Regioselectivity
Ó 2009 Elsevier Ltd. All rights reserved.
Complexes with transition metals
1. Introduction
1,2,4,5-tetrakis(pyrazol-1-yl)benzene (5) in moderate yield by nu-
cleophilic substitution of bromine in 1,2,4,5-tetrabromobenzene,
Pyrazole-based chelating ligands have attracted significant
attention since their first introduction in 1966.1 Currently, the rep-
resentatives of this family that hold the most interest are poly-
pyrazolylborates (scorpionates) 1 (Fig. 1),2 polypyrazolylmethanes
2,3,4 and 2,6-bis(pyrazolyl)pyridines 3.5
On the other hand, few groups have researched polykis(pyrazol-
1-yl)benzenes, possibly due to difficulties concerning their prepa-
ration. To date only two such compounds have been studied (Fig. 2).
The Elguero group focused on hexakis(pyrazol-1-yl)benzene (4),
prepared in high yield by nucleophilic substitution of fluorine in
hexafluorobenzene.6,7 The Hosseini group reported synthesis of
although no data for this compound were given except the X-ray
structure and the formation of an unusual metallocyclophane upon
complexation with Cu(II).8
In addition, our group has successfully used nucleophilic substitu-
tion of fluorine in the preparation of polykis(dialkylamino)benzenes9
and phosphine ligands,10 and more recently we have demonstrated
the advantage of fluorine nucleophilic substitution over Buchwald–
Hartwig C–N cross-coupling in the preparation of 1,2-bis(pyrazol-1-
yl)benzene (6) (Scheme 1).11 Taking into account both our own results
and those of the aforementioned groups, we decided to develop
a general approach to chelating polykis(pyrazol-1-yl)benzenes start-
ing from polyfluoroarenes with a particular fluorine orientation.
N
N
N
N
N
N
N
N
B
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
N
1
2
3
N
N
N
Figure 1.
N
4
5
* Corresponding author. Tel./fax: þ7 863 297 5146.
E-mail address: vsorokin@aaanet.ru (V.I. Sorokin).
Figure 2.
0040-4020/$ – see front matter Ó 2009 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2009.04.035

O. Ivashchuk, V.I. Sorokin / Tetrahedron 65 (2009) 4652–4658
4653
benzene ring by 67ꢀ for the group containing protonated nitrogen
atom and by nearly 52ꢀ for the non-protonated nitrogen. In addi-
tion, the intermolecular hydrogen bond formed between the pyri-
dine atoms of different molecules had an N–H length of 0.860 Å and
an N/H length of 1.916 Å. Benzene rings in this assembly were
located at different sites of the plane, which encompasses atoms
involved in hydrogen bonds. It is obvious that the formation of such
a pair is more favorable than the more sterically strained and less
energetically effective seven-membered intramolecular bond.
To study the influence of solvent polarity on the reaction course,
we planned to test the reaction of sodium pyrazolide with 1,2,3,4-
tetrafluorobenzene (7), 1,2,4,5-tetrafluorobenzene (8), and hexa-
fluorobenzene in THF and DMF. DMSO was avoided, despite the
success with preparation of 6, because the mineral oil from NaH
dissolves slowly in this solvent, resulting in inconvenience.
The main question that arises before the start of any practical
work is the substitution pattern, namely the order in which the
fluorine atoms substitute. Previous investigations in related fields,
starting with the work of Chambers13 and including more recent
studies,14,15 have shown the applicability of the empirical rule: the
most favorable substitution site should have the greatest number of
neighboring ortho- and meta-fluorines. For example, in the case of
1,2,3,4-tetrafluorobenzene (7), the first substitution site is pre-
dicted to be F-2, followed by F-3. However, this rule was established
and tested using nucleophiles such as SRꢁ, ORꢁ, etc., which in-
troduce electron-donating groups to the molecule. In our case, we
aim to work with sodium pyrazolide, which introduces the slightly
electron-attracting pyrazolyl group to the polyfluoroaromatic
molecule. It may have a different influence on the substitution
pattern of subsequent pyrazolyls.
The substitution patterns observed experimentally in the re-
action of tetrafluorobenzene 7 with sodium pyrazolide, notewor-
thy, are in agreement with predictions based on empirical rule
(Scheme 2). The reaction begins with the substitution of the fluo-
rine atom at position 2, leading to product 9. Next, the fluorine at
position 3 is replaced, despite the fact that it seems sterically un-
favorable. The formation of 9, but not of the isomer with sub-
stitution of F-1, is supported by NMR data. For example, the 19F
NMR spectra contain only one 3JFF coupling constant near 20 Hz. It
is interesting to note that the amounts of 9 and 11 in the reaction
mass did not exceed several percent, even if 1 or 3 equiv of nu-
cleophile was used, and the main products are either 10 or 12. The
best conditions for preparation of 10 was the dropwise addition of
2 equiv of a solution of sodium pyrazolide in DMF to a solution of 7
in the same solvent at room temperature. In this case, 76% yield of
product can be achieved. If THF is used, good yields within a rea-
sonable time require heating of the reaction mass to 50 ꢀC. This
N
N
F
F
N
N
N
+
N
DMSO, 90 °C
24 h
Na+
6 (71%)
Scheme 1.
2. Results and discussion
2.1. Synthesis and structure
To provide the necessary pyrazol-1-yl groups’ arrangement ca-
pable of forming chelates with transition metals as starting points
for the investigation of nucleophilic substitution of fluorine, we
selected commercially available 1,2-difluoro-, 1,2,3,4-tetrafluoro-,
1,2,4,5-tetrafluoro-, and hexafluorobenzenes, the latter case chosen
to focus on finding optimal conditions for the isolation of the tet-
rasubstituted product, since 4 has been well studied previously.
Initially, we planned to gradually increase nucleophile strength to
avoid any uncontrolled reaction, especially in the case of highly
electron-deficient fluoroarenes. Pyrazole should be the least active,
followed by 1-(trimethylsilyl)-1H-pyrazole. In the latter case, the
formation of strong Si–F bonds during the reaction should cause it
to demonstrate greater activity in comparison with the pyrazole
and excellent selectivity in comparison with the corresponding
anion.12 Finally, sodium pyrazol-1-ide was chosen as the most ac-
tive compound. 1-(Trimethylsilyl)-1H-pyrazole was generated
without isolation by reaction of sodium pyrazol-1-ide with chloro-
trimethylsilane. However, neither of the aforementioned fluoroar-
omatics react with pyrazole itself, and only hexafluorobenzene
reacts with 1-(trimethylsilyl)-1H-pyrazole, leading to a mixture of
products after 7 days. Thus, only the results for sodium pyrazolide
are further presented.
1,2-Bis(pyrazol-1-yl)benzene (6) was prepared for subsequent
investigations according to our previous method.11 We did not
succeed in growing crystals of neutral 6 to confirm and study its
structure. However, taking into account its basic nature, it looks
more promising to prepare a salt of 6 with a strong acid. This was
also of interest to determine whether this salt would form a seven-
membered intramolecular hydrogen bond between pyridine-type
nitrogens of the neighboring pyrazole rings. The X-ray data of 1-(2-
(pyrazol-1-yl)phenyl)pyrazol-2-ium perchlorate confirmed the
structure of the parent compound. However, greater interest lies in
the formation of crystals of the assembly between two protonated
molecules (Fig. 3), in which the pyrazolyl groups deviate from the
Figure 3. 1-(2-(Pyrazol-1-yl)phenyl)pyrazol-2-ium perchlorate (6$HClO4) molecule assembly crystal form, according to X-ray. Hydrogen atoms, with the exception of those involved
in intermolecular hydrogen bonding, were omitted for clarity.

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O. Ivashchuk, V.I. Sorokin / Tetrahedron 65 (2009) 4652–4658
F
F
F
F
F
N
F
F
N
F
N
N
N
N
F
N
N
N
N
+
N
+
+
F
F
N
N
F
N
+
N
Na+
+
+
F
F
F
F
Na+
N
F
7
9
10
F
N
8
13
14
N
N
N
N
F
N
N
N
N
N
N
N
+
N
N
+
N
N
N
F
N
N
+
+
N
N
N
N
N
N
N
11
12
N
N
Scheme 2.
15
5
leads to some loss of selectivity and the isolated yield drops to 52%,
since 12 is formed as a by-product. On the other hand, the tetra-
substituted derivative 12 can be prepared by the addition of 4 equiv
of sodium pyrazolide to 7, either in DMF or in THF, both at 50 ꢀC,
with 94 and 71% isolated yields, respectively.
Unfortunately, we cannot grow suitable crystals of 10 or its salts
to verify the substitution pattern with the one established by het-
eronuclear NMR to check whether this was a case of formation of
same assembly, as it was for 6$HClO4. However, the structure of the
fully substituted derivative 12 was determined (Fig. 4).
In crystals of compound 12, pyrazolyl groups deviate from the
plane of the benzene ring, but if less sterically strained pyrazolyl
groups at 1 and 4 positions bend at an angle of 35ꢀ, more strained
rings at positions 2 and 3 deviate by a much greater angle of 73ꢀ. In
addition, pyridine nitrogens are in turn above–under–above–under
the benzene plane, possibly to reduce repulsion of their lone pairs.
The reaction of a nucleophile with 1,2,4,5-tetrafluorobenzene
(8) proceeds according to Scheme 3. In this case, however, we were
not able to detect monosubstituted derivative 13 in the reaction
mass. Additionally, the amount of 15 did not exceed 2%, regardless
of the conditions used.
Scheme 3.
preparation of 14. The main product obtained in this solvent, irre-
spective of the amount of nucleophile used, is tetrasubstituted
derivative 5, and the isolated yield of 14 did not exceed 20%. The 19F
NMR spectrum of 14 has no F–F coupling, and the 13C spectrum
contains signals from 6 carbon atoms. In DMF, we succeeded in
reaching greater selectivity toward a disubstituted derivative by
dropwise addition of the nucleophile to 8 at rt, obtaining a mixture
containing 67% of 14 and 23% of 5, but the isolated yield of 14 was
only 25%. Increasing the temperature increases the conversion but
lowers the selectivity toward 14. For example, at 50 ꢀC, the mixture
consists of 45% of 14 and 54% of 5, but the isolated yield of 14 in-
creased to 36%.
Tetrasubstituted derivative 5, on the other hand, can be pre-
pared with good yields either in THF or in DMF, but in all cases,
heating is required to achieve full transformation. For a reaction
conducted in THF, the yield was 72%, and in DMF, it increased to
83%. It should be noted that substitution of fluorine is a much more
effective method for preparation of 5 compared to substitution of
bromine (68% yield) or chlorine (8%) atoms in corresponding
1,2,4,5-tetrahalobenzenes, as done by the Hosseini group.8
Hexafluorobenzene was the most electron-deficient fluorocar-
bon among those used in this work, and its reaction with sodium
pyrazolide was expected to be less controllable. Since we were not
interested in hexasubstituted derivative 4, all our attempts were
focused on the preparation of tetra- and disubstituted derivatives.
Reactions in THF were mostly disappointing since, due to the very
low solubility of 4 in this solvent, even if 2 or 4 equiv of nucleophile
was used, the reaction resulted in substantial amounts of 4. For
example, the reaction of hexafluorobenzene with 2 equiv of sodium
pyrazolide at rt produces a mixture containing 46% of di- (16), 4% of
tetra- (17), and 50% of hexasubstituted (4) derivative (Scheme 4);
no other products were detected in the reaction mass. The presence
of only one singlet in the 19F NMR spectrum of the disubstituted
productconfirms theformationof16 andindicates nodeviationfrom
the previously observed substitution pattern for other nucleo-
philes.9,14,15 Reaction in DMF proceeds more selectively, but in this
case we also did not detect any other products besides 16, 17, and 4.
More suitable conditions for preparation of 16 were found to be
dropwise addition of 2 equiv of nucleophile to hexafluorobenzene
at rt, giving a mixture of 16 (65%), 17 (32%), and 4 (3%), from which
the disubstituted derivative can be isolated in 35% yield, along with
18% of 17. However, to prepare 17, it was more effective to add
4 equiv of sodium pyrazolide to hexafluorobenzene under the same
conditions, which gave a mixture of 17 (79%) and 4 (21%); the
isolated yield of tetrasubstituted derivative was then 55%.
Compound 14 is desired as a possible precursor of ‘mixed’ li-
gands, containing pyrazolyl groups and other substituents with
lone electron pairs capable of forming complexes with metals.
However, we found that THF is not a good solvent for the
Figure 4. Crystal structure of 1,2,3,4-tetrakis(pyrazol-1-yl)benzene (12); hydrogen
atoms are omitted for clarity.

O. Ivashchuk, V.I. Sorokin / Tetrahedron 65 (2009) 4652–4658
4655
nucleophile and highly reactive perfluoroaromatic electrophiles, an
early TS is formed and the regiochemistry is, therefore, dominated
by polar effects in the initial states, making activation by fluorine
ortho- to the site of nucleophilic attack dominant, similar to
established by Chambers for other nucleophilic substitution re-
actions involving polyfluoroaromatics.14
N
N
F
F
F
F
F
F
F
F
F
F
N
+
+
N
Na+
N
N
2.2. Complexation with Cu(II) and Pd(II)
16
Cu(II) and Pd(II) were selected as central ions for studying the
complexation ability of synthesized compounds 5, 6, 10, 12, and 17.
Complexes were prepared from appropriate amounts of
CuCl2$2H2O or PdCl2(CH3CN)2 and ligand in methanol for copper or
dichloromethane for palladium. The resulting complexes were
isolated in the solid state for subsequent investigation. For 6 and 10,
only the 1:1 (metal/ligand) composition was studied; for ligands 5,
12, and 17, the 2:1 ratio was also analyzed to investigate the pos-
sibility of forming bidentate complexes. Electrospray ionization
mass spectrometry (ESI-MS) was used to elucidate the formation of
complexes and their composition. We also intended to utilize NMR
spectroscopy to study Pd complexes, but their very low solubility
did not permit this.
There are some similarities as well as differences in mass spectra
of 6 and 10 copper complexes. First, both spectra showed clear
signals corresponding to [Cu2L2Cl3]þ dimeric species (for example,
with mass 652 in the case of 6) as well signals that can be attributed
to [CuL]þ ions (for example, with mass 309 for 10). The latter
resulted from the reduction of Cu2þ to Cuþ, often observed for
copper in ESI-MS.16 On the other hand, in the mass spectra of 10
complex with copper, in contrast to 6, signals assigned to [CuL2Cl]þ
and [CuL2]þ were observed, indicating the tendency of this ligand
to form 1:2 species in solution. Formation of dimeric species
[Cu2L2Cl3]þ in solution correlates with X-ray data for the crystal of
10 copper complex (Fig. 6), in which two structurally independent
dimeric species with bridge chlorine atoms are present.
Another peculiarity of the presented structure is the formation
of a seven-membered metallo-ring with Cu1–N2 length of 2.033 Å;
Cu1–N4d2.019 Å; Cu10–N10d2.008 Å; Cu10–N40d1.997 Å; Cu1–
Cl1d2.252 Å; Cu10–Cl10d2.225 Å; Cu1–Cl2d2.286 and 2.563 Å;
Cu10–Cl20d2.290 and 2.697 Å. The coordination sphere around the
pentacoordinated Cu(II) cation is composed of two nitrogen atoms
and three chloride anions, producing a distorted square pyramidal
geometry.
Potential bidentate ligands 5 and 17 demonstrate similarities
with their monodentate analogs 6 and 10 in complexation with
copper when a 1:1 metal/ligand composition was used. In both
cases, signals corresponding to [Cu2L2Cl3]þ and [CuL]þ were present
in the mass spectra. For 17, there was an additional signal that can be
assigned to the [CuL2]þ species. Unfortunately, we were not able to
N
N
N
F
F
N
N
N
N
N
N
N
N
N
N
N
+
+
N
N
N
N
N
N
17
4
Scheme 4.
We were interested in the crystal structure of 17 to compare it
with published data for 5 and to observe the influence made by the
fluorine atoms. Unfortunately, we only succeeded in growing
crystals of the diprotonated salt with perchloric acid. As one can see
from Figure 5, intermolecular hydrogen bonds were formed be-
tween 17$2HClO4 and two water molecules, with an N–H bond
length of 0.900 Å and an O/H length of 1.733 Å. Formation of such
shorter and less hindered bonds with small water molecules may
prevent formation of any assemblies between 17$2Hþ fragments.
Bend angles of pyrazolyl groups from the benzene ring plane were
very close to those observed for 6$HClO4, near 63ꢀ for protonated
groups and near 55ꢀ for neutrals. It is also interesting that, due to
the formation of short contacts between the N4 atom of one mol-
ecule and the hydrogen atom bonded to C4 of the other molecule,
and possibly also due to the repulsion by the fluorine atom electron
shell, we did not observe the nitrogen atom arrangement pattern of
above–under–above–under relative to the benzene ring plane, as
seen for 12 or reported for 5 by Hosseini.8
In conclusion to this section, the agreement between the site of
the nucleophile attack, predicted on the base of empirical rule and
the experimentally observed pattern should be noted, indicating
that the regioselectivity of these processes depends upon the re-
activity of the nucleophile and the electrophile, which affects the
position of the transition state. For the highly reactive pyrazolide
Figure 5. Crystal structure of 1,10-(2,5-di(1H-pyrazol-1-yl)-1,4-phenylene) bis(1H-
pyrazol-2-ium) diperchlorate (17$2HClO4); hydrogen atoms, except those involved in
hydrogen bonding and perchlorate anions, are omitted for clarity.
Figure 6. Crystal structure of Cu(II) complex with 10 as ligand. For clarity, most atom
labels, except for the coordination sphere, are omitted.

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O. Ivashchuk, V.I. Sorokin / Tetrahedron 65 (2009) 4652–4658
grow suitable crystals to elucidate the type of coordination realized
in this case in solid state. However, the presence of [Cu2L2Cl3]þ in
solution can indicate the formation of either metallocyclophane
type species, as reported by Hosseini,8 or dimeric species with
bridged chlorines, similar to that shown in Figure 6. It is interesting
that the copper complex with ligand 12 demonstrated different
behaviors in solution. Only one signal, corresponding to the [CuL]þ
species, was present in the mass spectrum. This may indicate that
steric complications, due in this case to the presence of neighboring
pyrazolyl groups, prevent dimeric species from forming. If a 2:1
(copper/ligand) composition was used, the results were not as clear.
In all cases in the mass spectra, signals corresponding to the [CuL]þ
species were present. Furthermore, in the cases of 10 and 17, signals
that can be attributed to [Cu2LCl]2þ with masses 505 and 541, re-
spectively, were also observed. When 5 was used as the ligand, all
signals in the mass spectrum were at noise level, indicating low
solubility of the formed complexes, although in this case, a signal
corresponding to [CuL]þ was present. As a result, ESI-MS data does
not allow definite claims about the formation of 2:1 complexes, and
additional investigation using other methods is required.
The mass spectra of all 1:1 palladium complexes contained
masses corresponding to [PdLCl]þ and [Pd2L2Cl3]þ species. But also
a lot of signals, which we cannot interpret unambiguously, pre-
sented, possibly indicating complex interactions of metal and li-
gand in solution and fragmentations undergone by complexes. On
the other hand, X-ray data for crystals grown from the 1:1 complex
of Pd(II) and ligand 6 show the formation of a seven-membered
metallo-chelate (Fig. 7).
In these crystals, two independent units were present, similar to
those observed with copper. Selected parameters are: Pd1–
N1d2.010; Pd1–N3d2.013; Pd1–Cl1d2.282; Pd1–Cl2d2.288; Pd2–
N5d2.006; Pd2–N7d2.020; Pd2–Cl3d2.269; Pd2–Cl4d2.292 Å;
N3–Pd1–Cl1 angled90.01ꢀ; and N1–Pd1–N3d87.48ꢀ. The co-
ordination sphere around the tetracoordinated Pd(II) cation is com-
posed of two nitrogen atoms and two chloride anions, giving
a distorted square geometry; the angle betweenplane drawnthrough
Cl1, Pd1, Cl2 and plane N3, Pd1, N3 is 5.79ꢀ; in the other unit, it is 5.21ꢀ.
If the 2:1 (palladium/ligand) composition was used, potential
bidentate ligands 5, 10, 12, and 17 showed similarities in ESI-MS. In
all spectra, signals corresponding to [PdL]þ and [Pd2L2Cl3]þ were
observed. Furthermore, signals attributed to [Pd2LCl3]þ and
[Pd2LCl2]2þ were present, indicating formation of the desired
complexes.
In conclusion, a simple method for the preparation of previously
little-known polykis(pyrazol-1-yl)benzenes is presented based on
nucleophilic substitution of fluorine in polyfluoroaromatic compounds
by sodium pyrazolide. Using this method, a series of potential chelating
ligands for transition metals were made, and their complexation abil-
ities toward copper(II) and palladium(II) were demonstrated.
3. Experimental section
3.1. General remarks
Polyfluoroaromatics and 60% suspension of NaH in mineral oil
were purchased from Alfa Aesar. THF, DMF, and DMSO were puri-
fied and made anhydrous according to literature procedures.17 NMR
spectra were recorded on a Varian Unity-300. 1H NMR and 13C NMR
spectra were recorded using Me4Si as an internal standard. 19F NMR
was recorded using CFCl3 as an internal standard. EI mass spectra
were recorded on Finnigan Mat. INCOS 50 at 70 eV. ESI-MS spectra
were recorded on Finnigan Mat. LSQ-ms; acetone or acetonitrile
was used as solvent.
3.2. Nucleophilic substitution of fluorine
3.2.1. General procedure
To a stirred solution of pyrazole (1 mmol) in the selected solvent
(5 mL), 1 mmol of 60% suspension of NaH in mineral oil was added
(CAUTION! Rapid hydrogen evolution). The reaction mass was
stirred for 30 min, and the resulting sodium pyrazolide was added
dropwise to a solution of the corresponding amount of a poly-
fluoroaromatic compound in the same solvent. The resulting so-
lution was stirred for 10 h at the selected temperature and then
poured into water. Products were extracted with CH2Cl2; the or-
ganic phase was dried with Na2SO4 and evaporated to dryness. The
residue was either crystallized from the appropriate solvent or
separated by column chromatography.
3.2.2. 1,4-Difluoro-2,3-bis(pyrazol-1-yl)benzene (10)
Compound 10 was prepared according to the general procedure
using DMF as the solvent and 2 equiv of nucleophile at rt. Yield was
76%, with colorless plates from diethyl ether, mp 133–134 ꢀC;
[Found: C, 58.52; H, 3.28; N, 22.78. C12H8F2N4 requires: C, 58.54; H,
3.27; N, 22.76%]; nmax (KBr) 3101, 1594, 1529, 1392, 1245, 1043,
837 cmꢁ1 dH (300 MHz, CDCl3) 6.28 (2H, dd, J 2.5, 1.9 Hz, H-40
;
(pyrazolyl)), 7.30 (2H, m, J 8.3, 6.1, 4.9 Hz, H-5,6), 7.32 (2H, dd, J
0.5 Hz, H-50 (pyrazolyl)), 7.60 (2H, dd, H-30 (pyrazolyl)); dC (63 MHz,
CDCl3) 153.76 (dd, J 252.1, 4.2 Hz, C-1,4), 141.83 (s, C-30 (pyrazolyl)),
132.15 (s, C-50 (pyrazolyl)), 126.92 (dd, J 10.1, 6.7 Hz, C-2,3), 117.21
(dd, J 17.5, 13.9 Hz, C-5,6), 107.37 (s, C-40 (pyrazolyl)); dF (272 MHz,
CDCl3) ꢁ147.65 (dd, F-1,3); m/z (EI) 246 (100, Mþ), 245 (84), 218
(41), 206 (21), 165 (26), 139 (19), 112 (26), 52 (29), 39 (22%).
3.2.3. 1,2,3,4-Tetrakis(pyrazol-1-yl)benzene (12)
Compound 12 was prepared according to the general procedure
using DMF as the solvent and 4 equiv of nucleophile at 50 ꢀC. Yield
was 94%, with colorless needles from methanol, mp 213–214 ꢀC;
[Found: C, 63.10; H, 4.13; N, 32.75. C18H14N8 requires: C, 63.15; H,
4.12; N, 32.73%]; nmax (KBr) 3118, 1606, 1517, 1396, 1195, 1041,
763 cmꢁ1 dH (300 MHz, CDCl3) 6.22 (2H, dd, J 2.4, 1.9 Hz, H-400 (2,3-
;
pyrazolyl)), 6.22 (2H, dd, J 2.6, 1.8 Hz, H-40 (1,4-pyrazolyl)), 6.76 (2H,
dd, J 0.5 Hz, H-50 (1,4-pyrazolyl)), 7.29 (2H, dd, J 0.6 Hz, H-500 (2,3-
pyrazolyl)), 7.55 (2H, dd, H-300 (2,3-pyrazolyl)), 7.63 (2H, dd, H-30
(1,4-pyrazolyl)), 8.17 (2H, s, H-5,6); dC (63 MHz, CDCl3) 141.58 (s, C-
30 (1,4-pyrazolyl)), 141.38 (s, C-300 (2,3-pyrazolyl)), 136.85 (s, C-1,4),
132.47 (s, C-50 (1,4-pyrazolyl)), 131.22 (s, C-2,3), 129.79 (s, C-5,6),
Figure 7. Structure of Pd(II) and ligand 6 1:1 complex, according to X-ray data. Hy-
drogen atoms are not shown.

O. Ivashchuk, V.I. Sorokin / Tetrahedron 65 (2009) 4652–4658
4657
126.61 (s, C-500 (2,3-pyrazolyl)), 108.05 (s, C-400 (2,3-pyrazolyl)),
3.3. Preparation of complexes
107.38 (s, C-40 (1,4-pyrazolyl)); m/z (EI) 342 (100, Mþ), 341 (88), 314
(13), 246 (13), 207 (13), 180 (18), 168 (23), 103 (23), 79 (34), 64 (41),
57 (44), 52 (73), 44 (76), 39 (61%).
To prepare the Cu(II) complexes, 1 or 2 equiv of CuCl2$2H2O
solution in methanol (3 mL) was added to a stirred solution of li-
gand (0.1 mmol) in CH2Cl2 (3 mL). The reaction mass was stirred
overnight, and the precipitated complex was isolated by filtration,
washed with methanol, and dried for subsequent analysis by ESI-
MS or crystal growth.
To prepare the Pd(II) complexes, 1 or 2 equiv of PdCl2(CH3CN)2
solution in CH2Cl2 (3 mL) was added to a stirred solution of ligand
(0.1 mmol) in CH2Cl2 (3 mL). The reaction mass was stirred over-
night, and the precipitated complex was isolated by filtration,
washed with CH2Cl2, and dried for subsequent analysis by ESI-MS
or crystal growth.
3.2.4. 1,4-Difluoro-2,5-bis(pyrazol-1-yl)benzene (14)
Compound 14 was prepared according to the general procedure
using DMF as the solvent and 2 equiv of nucleophile at 50 ꢀC. To
isolate 14, the crude reaction mass was separated by column chro-
matography on alumina using CHCl3/hexanes (2:1) as eluent.
Isolated yield was 36%, with colorless crystals from CHCl3, mp 140–
141 ꢀC; [Found: C, 58.54; H, 3.26; N, 22.77. C12H8F2N4 requires: C,
58.54; H, 3.27; N, 22.76%]; nmax (KBr) 3124, 1633, 1539, 1473, 1402,
1191, 1035, 937, 771 cmꢁ1
; dH (300 MHz, CDCl3) 6.49 (2H, dd, J 2.5,
1.9 Hz, H-40 (pyrazolyl)), 7.73 (2H, d, H-50 (pyrazolyl)), 7.90 (2H, dd, J
9.2, 9.2 Hz, H-3,6), 8.07 (2H, br m, H-30 (pyrazolyl)); dC (63 MHz,
CDCl3) 149.07 (dd, J 246.5, 3.7 Hz, C-1,4), 141.52 (s, C-30 (pyrazolyl)),
130.83 (dd, J 14.9, 8.3 Hz, C-3,6), 112.06 (dt, J 18.0, 5.4 Hz, C-2,5),
108.48 (s, C-40 (pyrazolyl)); dF (272 MHz, CDCl3) ꢁ128.43 (2F, dd, F-
1,4); m/z (EI) 246 (100, Mþ), 218 (4),191 (6),167 (11),152 (7),125 (7%).
3.4. X-ray crystallographic analysis
Crystals of the compounds were grown by slow evaporation of
their solutions in methanol (6$HClO4, 12, 17$2HClO4, and Pd(II)
complex of 6) or CH2Cl2 (Cu(II) complex of 10). The data were col-
lected on a Bruker SMART 1000 CCD diffractometer using Mo K
a
3.2.5. 1,2,4,5-Tetrakis(pyrazol-1-yl)benzene (5)
radiation. SHELX-97 provided the method of absorption correction,
Compound 5 was prepared according to the general procedure
using DMF as the solvent and 4 equiv of nucleophile at 50 ꢀC. Yield
was 83%, with colorless crystals from methanol, mp 204–205 ꢀC;
[Found: C, 63.12; H, 4.10; N, 32.74. C18H14N8 requires: C, 63.15; H,
4.12; N, 32.73%]; nmax (KBr) 3101, 1539, 1481, 1407, 1319, 1197, 1047,
method of solution, and refinement.18
3.4.1. Compound 6$HClO4
C12H11N4ClO4 M¼310.70, monoclinic, space group P21/c,
a¼8.6564(5), b¼14.3458(9), c¼10.6481(7) Å,
b
¼96.3130(10)ꢀ,
777 cmꢁ1
;
dH (300 MHz, CDCl3) 6.32 (4H, dd, J 2.5, 1.8 Hz, H-40
V¼1314.29(14) Å3, Z¼4,
r
¼1.570 g cmꢁ3
,
crystal size¼0.35ꢂ
(pyrazolyl)), 7.05 (4H, dd, J 0.4 Hz, H-50 (pyrazolyl)), 7.70 (4H, dd, H-
30 (pyrazolyl)), 8.09 (2H, s, H-3,6); dC (63 MHz, CDCl3) 142.01 (s, C-30
(pyrazolyl)), 133.97 (s, C-1,2,4,5), 130.68 (s, C-50 (pyrazolyl)),þ125.47
(s, C-3,6), 108.36 (s, C-40 (pyrazolyl)); m/z (EI) 342 (100, M ), 341
(47), 314 (6), 287 (6), 171 (11), 157 (12), 130 (9), 117 (9), 103 (9), 76
(20), 52 (53), 39 (35%).
0.30ꢂ0.20 mm, T¼120 K; 13,032 reflections measured, 3125 unique
(Rint¼0.0229), which were used in all calculations, cut-off criterion
I>2\s(I),
m
¼0.314 mmꢁ1, the final R and wR(F2) were 0.0423, 0.0759
(all data), residual electron density max, min 0.332, ꢁ0.441 e Åꢁ3
.
3.4.2. Compound 12
C18H14N8 M¼342.37, monoclinic, space group C2/c, a¼20.966(2),
3.2.6. 1,2,4,5-Tetrafluoro-3,6-bis(pyrazol-1-yl)benzene (16)
b¼9.0322(13), c¼9.2325(11) Å,
b
¼111.202(4)ꢀ, V¼1630.0(4) Å3,
Compound 16 was prepared according to the general procedure
using DMF as the solvent and 2 equiv of nucleophile at rt. To isolate
16, the crude reaction mass was separated by column chromato-
graphy on alumina using CHCl3 as eluent. Isolated yield was 35%,
with colorless crystals from methanol, mp 161–162 ꢀC; [Found: C,
51.04; H, 2.16; N, 19.86. C12H6F4N2 requires: C, 51.07; H, 2.14; N,
Z¼4,
r
¼1.395 g cmꢁ3, crystal size¼0.60ꢂ0.20ꢂ0.15 mm, T¼100 K;
8179 reflections measured, 1756 unique (Rint¼0.0607), which were
used in all calculations, cut-off criterion I>2\s(I),
m
¼0.091 mmꢁ1
,
the final R and wR(F2) were 0.0664, 0.0971 (all data), residual
electron density max, min 0.219, ꢁ0.240 e Åꢁ3
.
19.85%]; nmax (KBr) 3126, 1540, 1392, 1176, 1087, 987, 775 cmꢁ1
; dH
3.4.3. Compound 17$2HClO4
(300 MHz, CDCl3) 6.59 (2H, dd, J 2.5, 1.9 Hz, H-40 (pyrazolyl)), 7.77
(2H, dd, J 0.1 Hz, H-50 (pyrazolyl)), 7.87 (2H, dd, H-30 (pyrazolyl)); dC
(63 MHz, CDCl3) 142.82 (s, C-30 (pyrazolyl)), 132.24 (s, C-50 (pyr-
azolyl)), 108.22 (s, C-40 (pyrazolyl)); dF (272 MHz, CDCl3) ꢁ170.22 (4F,
s); m/z (EI) 282 (100, Mþ), 228 (8), 215 (10), 209 (16), 203 (26), 188
(21), 161 (26), 148 (19), 117 (16), 98 (16), 69 (17), 52 (31), 40 (34%).
C18H20N8Cl2F2O8 M¼585.32, triclinic, space group P-1,
a¼7.1932(8), b¼9.4900(11), c¼9.8025(11) Å,
a¼76.255(2)
b
¼
70.499(2),
g
¼74.909(2)ꢀ, V¼600.61(12) Å3, Z¼1,
r
¼1.618 g cmꢁ3
,
crystal size¼0.35ꢂ0.30ꢂ0.20 mm, T¼100 K; 6943 reflections mea-
sured, 3412 unique (Rint¼0.0289), which were used in all calcula-
tions, cut-off criterion I>2\s(I),
m
¼0.349 mmꢁ1, the final R and
wR(F2) were 0.0775, 0.1102 (all data), residual electron density max,
3.2.7. 1,4-Difluoro-2,3,5,6-tetrakis(pyrazol-1-yl)benzene (17)
min 0.392, ꢁ0.353 e Åꢁ3
.
Compound 17 was prepared according to the general procedure
using DMF as the solvent and 4 equiv of nucleophile at rt. To isolate
17, the crude reaction mass was separated by column chromato-
graphy on alumina, using CHCl3 as eluent. Isolated yield of product
was 55%, with colorless crystals from methanol, mp 257–258 ꢀC;
[Found: C, 57.13; H, 3.22; N, 29.60. C18H12F2N8 requires: C, 57.14; H,
3.20; N, 29.62%]; nmax (KBr) 3120, 1633, 1535, 1486, 1396, 1049, 952,
3.4.4. Cu(II) complex of 10
C12H8N4Cl2F2Cu M¼380.66, monoclinic, space group P21/c,
a¼15.915(4), b¼14.063(3), c¼13.560(3) Å,
b
¼106.267(4)ꢀ, V¼
2913.4(11) Å3, Z¼8,
r
¼1.736 g cmꢁ3
,
crystal size¼0.45ꢂ0.30ꢂ
0.20 mm, T¼120 K; 28,591 reflections measured, 6939 unique
(Rint¼0.0943), which were used in all calculations, cut-off criterion
858, 748 cmꢁ1
;
dH (300 MHz, CDCl3) 6.38 (4H, dd, J 2.5, 1.8 Hz, H-40
I>2\s(I),
m
¼1.884 mmꢁ1, the final R and wR(F2) were 0.1074, 0.1153
(pyrazolyl)), 7.47 (4H, dd, H-50 (pyrazolyl)), 7.67 (4H, dd, H-30
(pyrazolyl)); dC (63 MHz, CDCl3) 148.00 (dd, J 255.3 Hz, C-1,4),
142.42 (s, C-30 (pyrazolyl)), 132.24 (s, C-50 (pyrazolyl)), 127.01 (m, C-
2,3,5,6), 107.95 (s, C-40 (pyrazolyl)); dF (272 MHz, CDCl3) ꢁ153.74
(2F, s); m/z (EI) 282, 378 (53, Mþ), 243 (6), 216 (8), 189 (12), 175 (13),
162 (12), 150 (12), 124 (12), 112 (13), 100 (14), 94 (26), 79 (31), 69
(19), 52 (100), 39 (74%).
(all data), residual electron density max, min 0.989, ꢁ0.494 e Åꢁ3
.
3.4.5. Pd(II) complex of 6
C12H10N4Cl2Pd M¼387.54, monoclinic, space group P21/c,
a¼7.2352(4), b¼27.9533(16), c¼13.3461(8) Å,
b
¼100.0030(10)ꢀ,
V¼2658.2(3) Å3, Z¼8,
r
¼1.937 g cmꢁ3, crystal size¼0.40ꢂ0.25ꢂ
0.20 mm, T¼120 K; 24,879 reflections measured, 5741 unique

4658
O. Ivashchuk, V.I. Sorokin / Tetrahedron 65 (2009) 4652–4658
3. Pettinari, C.; Pettinari, R. Coord. Chem. Rev. 2005, 249, 525–543.
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(Rint¼0.0711), which were used in all calculations, cut-off criterion
I>2\s(I),
m
¼1.787 mmꢁ1, the final R and wR(F2) were 0.0819, 0.0756
(all data), residual electron density max, min 1.549, ꢁ0.641 e Åꢁ3
.
Crystallographic data for the structures in this paper have been
deposited in the Cambridge Crystallographic Data Center as a supple-
mentary publication (6$HClO4, CCDC 718737; 12, CCDC 718736;
17$2HClO4, CCDC 718738; Cu(II) complexof 10, CCDC 718740 and Pd(II)
complex of 6, CCDC 718739). Copies of the data can be obtained, free of
charge, on application to CCDC, 12 Union Road, Cambridge CB12 1EZ,
UK [fax: þ44 1223 336033 or e-mail: deposit@ccdc.cam.ac.uk].
10. Sorokin, V. I.; Nieuwenhuyzen, M.; Saunders, G. C. Mendeleev Commun. 2006,
171–172.
Acknowledgements
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The authors wish to express their appreciation to Dr. Anatoly
Chernyshev and Prof. Valery Ozeryanskii for useful discussion and
assistance, and especially to Drs. Muir and Baker from Parallel
Quantum Solutions for quantum-mechanical predictions of sub-
stitution pattern, not included in this paper.
16. Henderson, W.; McIndoe, J. S. Mass Spectrometry of Inorganic and Organometallic
Compounds; John Wiley & Sons: Chichester, 2005.
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References and notes
18. Sheldrick, G. M. SHELX-97: Program for Crystal Structure Solution; University of
Goettingen: Goettingen, Germany, 1997.
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