Synthesis of the silver(I) complex of CH2[CH(pz 4Et)2]2 containing the unprecedented [Ag(NO3)4]3- anion: A general method for the preparation of 4-(alkyl)pyrazoles

Article abstract of DOI:10.1039/b307306h

A general two-step method for the syntheses of 4-(alkyl)pyrazoles has been developed. The first step involves the reaction between organyl diethylacetals and the Vilsmeier reagent to give a mixture of ethoxy-and dimethylamino- acroleins. This mixture reacts directly with hydrazine monohydrogenchloride to yield the desired (4-substituted)pyrazoles. The 4-(phenyl)pyrazole derivative exhibited a markedly lower solubility in common organic solvents. In the solid state structure the phenyl and pyrazolyl groups are nearly coplanar and extensive intermolecular CH-π interactions organize the molecules in two-dimensional sheets that are held in a three dimensional arrangement by NH...N hydrogen bonds. Tetrakis[(4-ethyl)pyrazolyl]propane, CH ₂[CH(pz^4Et)₂]₂, was prepared by a transamination reaction and reacts with Ag(NO₃) to yield a compound with a 4:3 metal:ligand mole ratio that when crystallized by diffusion of Et₂O into an acetone solution produced [Ag₂{μ-CH ₂[CH(pz^4Et)₂]₂}₂] ₃[Ag(NO₃)₄]₂ (1). This complex contains dimeric units in which two silver cations are sandwiched between two CH₂[CH(pz^4Et)]₂ ligands and the counterion is the unprecedented tetra(nitrato)argentate anion. ESI mass spectral data support the existence of both the cationic dimeric units and the [Ag(NO ₃)₄]^- anion in solution.

Full text of DOI:10.1039/b307306h

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Synthesis of the silver(I) complex of CH2[CH(pz4Et)2]2 containing the
unprecedented [Ag(NO3)4]3ꢀ anion: A general method for the
preparation of 4-(alkyl)pyrazolesy
Daniel L. Reger,*a James R. Gardinier,a T. Christian Grattan,b Monica R. Smithb and
Mark D. Smitha
a
Department of Chemistry and Biochemistry, University of South Carolina, Columbia,
South Carolina 29208, U.S.A. E-mail: reger@sc.edu
Department of Chemistry, Physics, and Geology, Winthrop University, Rock Hill,
South Carolina 29733, USA
b
Received (in New Haven, USA) 27th June 2003, Accepted 26th July 2003
First published as an Advance Article on the web 1st September 2003
A general two-step method for the syntheses of 4-(alkyl)pyrazoles has been developed. The first step
involves the reaction between organyl diethylacetals and the Vilsmeier reagent to give a mixture of ethoxy-
and dimethylamino- acroleins. This mixture reacts directly with hydrazine monohydrogenchloride to yield the
desired (4-substituted)pyrazoles. The 4-(phenyl)pyrazole derivative exhibited a markedly lower solubility in
common organic solvents. In the solid state structure the phenyl and pyrazolyl groups are nearly coplanar and
extensive intermolecular CH–p interactions organize the molecules in two-dimensional sheets that are held
in a three dimensional arrangement by NHꢁ ꢁ ꢁN hydrogen bonds. Tetrakis[(4-ethyl)pyrazolyl]propane,
CH2[CH(pz4Et)2]2 , was prepared by a transamination reaction and reacts with Ag(NO3) to yield a compound
with a 4 : 3 metal : ligand mole ratio that when crystallized by diffusion of Et2O into an acetone solution
produced [Ag2{m-CH2[CH(pz4Et)2]2}2]3[Ag(NO3)4]2 (1). This complex contains dimeric units in which two silver
cations are sandwiched between two CH2[CH(pz4Et)]2 ligands and the counterion is the unprecedented
tetra(nitrato)argentate anion. ESI mass spectral data support the existence of both the cationic dimeric
units and the [Ag(NO3)4]ꢀ anion in solution.
containers, molecular sensors and sieves.4,5 In an effort to
Introduction
more fully develop this chemistry, the efficient syntheses of
a variety of 4-substituted pyrazoles was needed to improve
the solubility characteristics and to provide a vehicle for
controlling the factors that dominate the supramolecular
structures of the new complexes while minimizing both steric
and electronic effects associated with replacing substituents
on the pyrazolyl group on their coordination behavior toward
As part of our ongoing interest in developing next-generation
scorpionate ligands, we have recently been exploring the chem-
istry of poly(pyrazolyl)methane ligands, the charge-neutral
analogues of the more familiar poly(pyrazolyl)borates initially
developed by Trofimenko.1 We are particularly interested in
the development of multitopic derivatives where poly(pyrazo-
lyl)methane units are joined by a variety of organic spacers
metal centers.6 While a few 4-substituted pyrazoles, H(pz4R
)
2
(Fig. 1), such as in CH2[CH(pz)2]2 and in C6H6ꢀn[CH2O-
(R ¼ Me, Br, I) are commercially available, the capability
for the methyl and halide groups to participate in non-covalent
interactions and our additional long term goal of impro-
ving the solubility characteristics of poly(pyrazolyl)methane
coordination complexes and coordination polymers pro-
mpted us to explore other groups, such as long chain alkyls,
as substituents.
CH2C(pz)3]n , (n ¼ 2, 4, pz ¼ pyrazolyl ring),3 for the develop-
ment of coordination polymers and discrete complexes with
unusual supramolecular structures. Research into these types
of complexes is driven by the fact that they can play a role
in catalysis, molecular recognition or can act as molecular
It was initially surprising that there are only sporadic reports
concerning the synthesis of pyrazoles substituted by simple
organyl groups solely at the 4-position.7–10 A series of 4-
(cycloalkyl)pyrazoles9e along with a 4-(2-pyrazinyl)pyrazole11
have been prepared from malonaldehyde precursors, Fig. 2a.
The inherent difficulty encountered in preparing and isolating
the logical 2-substituted malonaldehyde precursors has likely
hindered further research into this area. For instance, we
(and undoubtedly many others) have found that the Claisen
reaction between alkanals and ethyl formate affords the self-
condensation compounds (i.e., HC(O)CH(R)C(O)CH2R)
rather than the desired dialdehyde as the major product.
Therefore, the preparation of the desired malonaldehydes
requires indirect multi-step syntheses. Alternatively, malon-
aldehyde analogues have been used for pyrazole synthesis.
Fig. 1 Multitopic poly(pyrazolyl)methane ligands.
y Electronic supplementary information (ESI) available: Crystal pack-
ing diagram of the unit cell of [Ag2{l-CH2[CH(pz4Et)2]2}2]3[Ag-
(NO3)4]2(acetonex/Et2Oy). See http://www.rsc.org/suppdata/nj/b3/
b307306h/
1670
New J. Chem., 2003, 27, 1670–1677
DOI: 10.1039/b307306h
This journal is # The Royal Society of Chemistry and the Centre National de la Recherche Scientifique 2003

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Scheme 1
Results and discussion
Syntheses and characterization of 4-pyrazoles
The reaction between organyl diethylacetals and the Vilsmeier
reagent occurred smoothly at or below 80 ꢂC to give a mixture
of ethoxy- and dimethylamino- acroleins. A number of factors
were found to contribute to improving the overall yield of
the mixture and, hence, the desired pyrazole (Table 1) by the
current route. The temperature at which the Vilsmeier reaction
was carried out was found to be critical to the success of the
reactions; when the reactions were performed above 80 ꢂC
extensive decomposition occurred. Also, as can be expected
from the hydrolytic susceptibility of the acroleins and as was
indicated from the original report,13a after hydrolysis, the
extraction of the product mixture from the aqueous layer of
the Vilsmeier reaction is tedious since the partition coefficient
between the organic and aqueous phases slightly favors the
latter. The difficulty in separating the product mixture from
aqueous solution was partially alleviated by performing the
extraction from solutions that were either slightly acidic or
near neutral pH. The use of alkali metal carbonates or bicar-
bonates as bases was helpful toward providing a visual indica-
tion of neutralization (effervescence ceases). The extraction
process also varied in difficulty depending on the substituents
to be incorporated into the desired pyrazole and, consequently,
the nature of the organic substituent has a significant impact
on the overall yield of 4-(organyl)pyrazole (Table 1). It was
found that in the case of an ethyl substituent, the ethoxy acro-
lein is preferentially extracted with either diethyl ether or ben-
zene whereas the dimethylamino acrolein is preferentially
extracted with methylene chloride, so both solvents were used.
With longer chain alkyl derivatives (butyl or longer) the parti-
tion coefficient is increasingly in favor of the organic phase.
Furthermore, after extraction, it is necessary to remove any
DMF (reaction solvent) by vacuum distillation prior to reac-
tion with hydrazine. The dark residue that remains after
removal of the DMF is sufficiently pure to be used directly
for the preparation of the desired pyrazoles; significant
improvements in yield were not encountered by removing the
traces of highly-colored decomposition products from the resi-
dues. This beneficial feature eliminated the need for separation
of acroleins by vacuum distillation, a step that works well in
the case of the ethyl derivative but is more challenging for
the remaining derivatives owing to their relatively low volati-
lity and high melting points. Finally, the conversion of the
acrolein mixture to (4-substituted)pyrazoles is relatively
straightforward, but it should be noted that hydrazine mono-
hydrogenchloride was necessary for complete conversion
Fig. 2 Precursors to 4-(organyl)pyrazoles.
A series of 4-(alkyl)pyrazoles (and 2-malonaldehydes) have
been prepared by the reaction between hydrazine and either
2-substituted 1,1,3,3-tetraethoxypropanes8c (Fig. 2b) or acro-
lein derivatives7e,8a,9a,10f (Fig. 2c). It is noteworthy that the
2-substituted malonaldehydes depicted in Fig. 2a are prepared
by hydrolyzing either tetraalkoxypropanes or acroleins by first
basification with OHꢀ followed by acidification.9e,11
A feature common to the synthesis of most of the malon-
aldehydes analogues described above is the use of vinyl ethers
as starting materials. The vinyl ethers are typically prepared
by acid-catalyzed alcoholysis of alkanal diethylacetals.8c,12
In our hands this seemingly simple reaction failed to provide
useful quantities of vinyl ethers, regardlesss of the acid cata-
lyst used. Therefore, we sought alternative routes for the
synthesis of either 4-substituted pyrazoles or their malon-
aldehyde analogues.
One alternative approach to 4-substituted pyrazoles
described heating a POCl3-pyrazolinone mixture to above
200 ꢂC in a sealed glass vessel in one step and a sodium reduc-
tion of the resulting chloropyrazole in liquid ammonia in a
subsequent step.8c Both of these steps were deemed to be unne-
cessarily dangerous for the large quantity of pyrazole needed
for the preparation of useful quantities of poly(pyrazolyl)-
methane ligands. Therefore, we refocused our attention to
the preparation of acroleins as potential intermediates to
4-(organyl)pyrazoles.
It has long been known that the reaction between alkanꢀal
+
diacetals and the Vilsmeier reagent, [Me2N CHCl ][PO2Cl2
=
]
(derived from the stoichiometric reaction between DMF and
POCl3) or its chloride analogue (DMF and either phosgene
or oxalyl chloride) affords a mixture of acroleins of the type
HC(O)C(R)CH(X) (X ¼ NMe2 , OEt, Cl) where the dimethyl-
amino and ethoxy derivatives are usually the major pro-
ducts.13 We reasoned that it should be possible to use the
acrolein mixture directly for the preparation of 4-substituted
pyrazoles without the need for separation or conversion to
malonaldehydes prior to their reaction with hydrazine. This
report will document our successful endeavors in using this
simple, two-step approach for the preparation of a variety of
(4-organyl)pyrazoles as depicted in Scheme 1. In addition,
the derivatization of one 4-(alkyl)pyrazole, namely H(pz4Et),
to its tetrakis(pyrazolyl)propane derivative, and the subse-
quent coordination chemistry with silver nitrate will be
reported.
Table 1 Overall yields of 4-substituted pyrazoles from
RCH2CH(OEt)2
R group
Yield
ethyl
butyl
pentyl
44%
65%
58%
51%
47%
36%
rac-4-(a-ethyl)pentyl
cyclohexyl
phenyl
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since the dimethylamino acroleins remained unreacted when
hydrazine monohydrate was used.
The noncyclic alkyl substituted pyrazoles are either liquids
or low-melting solids (mp: ca. 23–25 ꢂC) that can be purified
by vacuum distillation at ca. 130 ꢂC/1 mm Hg while the cyclo-
hexyl and phenyl derivatives are solids that are best purified by
recrystallization. The phenyl derivative exhibited a markedly
lower solubility in common organic solvents when compared
to the remaining derivatives and prompted an investigation
into its solid-state structure (Fig. 3). It was found that the phe-
nyl and pyrazolyl groups are nearly coplanar with a dihedral
angle of 2.3ꢂ. This geometry favors extensive intermolecular
CH–p interactions such that two-dimensional sheets assemble
along the crystallographic bc plane as in Fig. 4. The assembly
occurs by tandem CH–p interactions between pyrazolyl
and phenyl groups in concurrence with edge-to-face (CH–p)
interactions between phenyl groups. Specifically, H3 of a
hydrogen-donating pyrazole interacts with the centroid of
the hydrogen-accepting phenyl grꢂoup of an adjacent pyrazole
˚
Fig. 4 Two-dimensional sheets formed by CH–p interactions in the
crystal of 4-(phenyl)pyrazole.
[C(3)H(3)ꢁ ꢁ ꢁcent. 2.516 A, 150.8 ] while the H(5) and H(6)
edge of the mean plane of one phenyl group is directed toward
the normal axis of the mean plane of an adjacent phenyl group
ꢂ
˚
[C(5)H(5)ꢁ ꢁ ꢁcent.(Ph) 3.204 A, 125.7 ; C(6)H(6)ꢁ ꢁ ꢁcent. 3.204
ꢂ
˚
complex of the CH2[CH(pz)2]2 ligand reported earlier, which
was insoluble in chloroform and only partially soluble in acet-
one. The NMR spectrum of the silver compound in either
CDCl3 or acetone shows equivalent pyrazolyl rings, as we have
observed previously with analogous complexes.
A, 125.7 ]. The sheets are stacked along the a-axis by NHꢁ ꢁ ꢁN
hydrogen bonds (Fig. 5). The equal population of the acidic
hydrogen over both nitrogens results in crystallographic disor-
der. The hydrogen bonding interaction of each component of
the disorder is unsymmetrical with NHꢁ ꢁ ꢁN distances and
ꢂ
ꢂ
˚
˚
angles of 2.02(2)A, 157(2) ; 1.98(2)A, 175(2) . The geometries
of all of the above non-covalent interactions are within typi-
cal values.2,5,14 The solid state structures of two forms of 4-
(pentyl)pyrazole monohydrogen chloride are provided in the
ESIz and further reveal the importance of hydrogen bonding
interactions in the solid state organization of pyrazole-based
compounds.
ð1Þ
Synthesis and characterization of
[Ag2{m-CH2[CH(pz4Et)2]2}2]3[Ag(NO3)4]2 (1)
Slow diffusion of Et2O into an acetone solution of the
Ag4L3(NO3)4 compound, afforded exceedingly fragile but well-
formed crystals of a solvate that were subjected to X-ray struc-
tural studies. The results of the study are shown in Fig. 6.
While the crystallographic data are of low quality, several
notable features can be clearly identified. First, in contrast to
the silver nitrate complex of its tetrakis(pyrazolyl)propane
counterpart derivative but similar to [Ag2{CH2[CH(pz)2]}2]-
(SO3CF3)2 , the two tetrakis[4-(ethyl)pyrazolyl]propane ligands
sandwich two silver cations forming a dimeric unit. In the
current case there are three distinguishable dications within
Tetrakis[(4-ethyl)pyrazolyl]propane, CH2[CH(pz4Et)2]2 , was
prepared by a transamination reaction (eqn. 1) similar to that
reported for the unsubstituted derivative CH2[CH(pz)2]2 .2 The
reaction between Ag(NO3) and CH2[CH(pz4Et)2]2 (L) in a 1 : 1
mol ratio in CH3CN afforded a compound with a 4 : 3 metal :
ligand mole ratio as indicated from its analytical data. The
compound exhibited excellent solubility in chlorinated sol-
vents, acetone, and acetonitrile in contrast to the silver nitrate
Fig. 3 Two views of the molecular structure of (4-phenyl)pyrazole
emphasizing (a) atom labeling scheme and (b) the coplanarity of
phenyl and pyrazolyl groups.
z CCDC reference numbers 216925–216928. See http://www.rsc.org/
suppdata/nj/b3/b307306h/ for crystallographic data in .cif or other
electronic format.
Fig. 5 Stacking of sheets by N–Hꢁ ꢁ ꢁN hydrogen bonding in the
structure of 4-(phenyl)pyrazole.
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Fig. 6 View of cation in [Ag2{m-CH2[CH(pz4Et)2]2}2]3[Ag(NO3)4]2 (1).
Fig. 8 ESI(ꢀ) Mass spectrum of [Ag2{m-CH2[CH(pz4Et)2]2}2]3-
[Ag(NO3)4]2 (1) after crystallization and removal of solvent by vacuum
distillation. Inset shows the observed (top) and calculated (bottom)
isotope pattern for the {[Ag2{m-CH2[CH(pz4Et)2]2}2][Ag(NO3)4]}ꢀ
anion.
the unit cell where the interatomic separations between silver
˚
centers in the dicationic units range between 3.75–4.03 A.
These distances are comparable to that found in [Ag2{CH2-
˚
[CH(pz)2]}2](SO3CF3)2 of 4.32 A and are longer than the upper
˚
weak intensity for [Ag2L(NO3)3]ꢀ, and of strong intensity for
the [Ag2(NO3)3]ꢀ, [Ag(NO3)2]ꢀ, and (NO3)ꢀ anions. The
ESI(+) mass spectral data show peaks of very weak intensity
for [Ag3L2(NO3)2]+ and [Ag3L2(NO3)2ꢁ(H2O)]+, peaks of
strong intensity for the monometallic [Ag(L)]+, [Ag(L)(CH3-
CN)]+ and [Ag(L)2]+ species, and peaks for [Ag2L2(NO3)]+.
The peaks for [Ag3L2(NO3)2]+ and [Ag3L2(NO3)2(H2O)]+
can be ascribed to be due to the {[Ag2L22+][Ag(NO3)2ꢀ]}+
ion pair and its water solvate where the tetra(nitrato)argentate
trianion fragments in the electrospray process, as also indi-
cated in the ESI(ꢀ) experiments. These peaks in the ESI(+)
support that the binuclear cations in 1 are retained under the
conditions of this experiment also indicating that the same
dimeric species exist in solution.
limit of 3.25 A usually attributed to significant Agꢁ ꢁ ꢁAg inter-
actions.15 Second, in agreement with charge balance and
the composition indicated by elemental analyses, two [tetra-
(nitrato)argentate(3ꢀ)] anions are found in the unit cell and
the geometry of these anions are found in Fig. 7. While the tet-
ra(nitrato)metallate anions of the group 12 elements are
known and have been structurally characterized,16 those of
the group 11 series are limited to derivatives in the divalent
state, Cu(II)16a and the unstable Ag(II) derivative17 but the lat-
ter has not been structurally characterized. This report pro-
vides the first synthesis and characterization of a group 11
tetra(nitrato)metallate trianion. Examination of the extended
structure of [Ag2L2]3[Ag(NO3)4]2ꢁ(Et2Ox/acetoney) (See ESIy)
reveals a highly porous framework where a mixture of disor-
dered diethylether and acetone solvent molecules of unknown
stoichiometry comprise ca. 45% of the total unit cell volume as
calculated by PLATON.23 The rapid gaseous diffusion of
solvent molecules from the highly porous solid framework is
thought to be responsible for the immediate cracking of the
crystals upon removal from the mother liquor, the crystal
instability with respect to thermal gradients, and the lack of
appreciable X-ray scattering above ca. 2y ¼ 40ꢂ.
Conclusions
A simple two-step preparation of 4-(organyl)pyrazoles has
been developed, carefully detailed, and found to be general
for a variety of substituents. The first crystal structures of
the mono 4-substituted pyrazoles have also been reported.
The supramolecular organization of 4-(phenyl)pyrazole by
intermolecular CH–p and by NHꢁ ꢁ ꢁN hydrogen bonding
interactions was observed in the solid state and accounts for
the low solubility of this derivative in common organic sol-
vents. The 4-(ethyl)pyrazole was successfully derivatized to
the corresponding tetrakis(pyrazolyl)propane ligand. The reac-
tion of CH2[CH(pz4R)2]2 and Ag(NO3) yields [Ag2{m-CH2-
[CH(pz4Et)2]2}2]3[Ag(NO3)4]2 (1), a complex that contains
dimeric units in which two tetrakis[4-(ethyl)pyrazolyl]propane
ligands sandwich two silver cations and contains the unpre-
cedented tetra(nitrato)argentate trianion. ESI mass spectro-
metric experiments indicate that the binuclear cations and
[Ag(NO3)4]3ꢀ trianion in 1 are retained in solution, but the
[Ag(NO3)4]3ꢀ trianion was prone to fragmentation. The low
quality of the crystal structure data and the different anions
did not permit a meaningful comparison of the aggregation
behavior of the [Ag2{CH2[CH(pz4R)2]2}2]2+ (R ¼ H and
R ¼ Et) dications, but the increased solubility of 1 indicates
that this substitution pattern will solve solubility problems
encountered in our development of the coordination chemistry
of multitopic ligands based on poly(pyrazolyl)methane units.
The general route to 4-substituted pyrazoles reported here is
of general use for the development of future poly(pyrazolyl)-
borate and poly(pyrazolyl)methane ligands designed for
specific characteristics.
ESI-mass spectral studies
The ESI(ꢀ) mass spectral data (Fig. 8) show peaks of weak
intensity at m/z ¼ 1411 and 990 corresponding to the
{[Ag2L22+][Ag(NO3)43ꢀ]}ꢀ and {[Ag2L2+][Ag(NO3)43ꢀ]}ꢀ
anions supporting the existence of the tetra(nitrato)argentate
trianion in solution. The peak at m/z ¼ 1411 also supports
the existence of the dimeric cation in solution. The fragmenta-
3ꢀ
tion of the Ag(NO3)4 trianion was indicated by peaks of
Fig. 7 View of the tetranitratoargentate(3ꢀ) anion.
New J. Chem., 2003, 27, 1670–1677
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J ¼ 7.2 Hz, 2 H, OCH2CH3), 2.22 (q, J ¼ 7.5 Hz, 2 H,
Experimental
CCH2CH3), 1.39 (t, J ¼ 7.2 Hz, 3 H, OCH2CH3), 0.98 (t,
J ¼ 7.5 Hz, 3 H, OCH2CH3). The residue (11.31 g, 88.9 mmol)
was 3-(dimethylamino)-2-ethyl-prop-2-enal 1H NMR (300
General comments
All reagents were used as purchased from Aldrich. Solvents
were commercially available, purified by conventional means,
and distilled immediately prior to use. Diethyl acetals RCH2-
CH(OEt)2 were prepared according to standard methodology
either by p-TsOH-catalyzed rearrangements of alkanals18
(R ¼ ethyl, butyl, pentyl) or by reactions of RCH2MgBr with
HC(OEt)3 (R ¼ pentyl, Et(Bu)CH, Ph, Cy).19 Silica gel (230–
400 mesh, 40–63 mm) was purchased from Fisher Scientific.
Robertson Microlit Laboratories, Inc. (Madison, NJ) per-
formed the elemental analyses. Samples for melting point
determinations were contained in flame sealed capillaries and
the reported temperatures are uncorrected. The NMR spectra
were recorded by using a Varian Mercury 300 or 400 MHz
instrument. Chemical shifts are reported in ppm and were
referenced to the solvent resonances as internal standards.
Mass spectrometric measurements recorded in ESI mode were
obtained on a Micromass Q-Tof spectrometer whereas those
performed by using direct probe analyses were made on a
VG 70S instrument.
Since the procedure used for the Vilsmeier formylation of
the following alkanal diethylacetals essentially followed that
described by Nair, Vietti, and Cooper20 for the formylation
of propionaldehyde diethylacetal, only the preparation of the
ethyl derivative will be detailed and only the quantities of
reagents used in this step of the preparation of the remaining
pyrazoles will be reported. The methods of extraction and pur-
ification were unique to each system under study, so these
procedures will be more detailed.
=
MHz, CDCl3) 8.83 (s, 1H, HC O), 6.46 (s, 1H, HC(NMe2)),
3.13 (s, 6 H, NMe2), 2.42 (q, J ¼ 7.5 Hz, 2 H, CCH2CH3),
1.02 (t, J ¼ 7.5 Hz, 3 H, OCH2CH3). The combined yield
(123 mmol) was 55% based on butyraldehyde diethyl acetal.
This mixture was dissolved in 100 mL MeOH, and 8.91 g of
NH2NH2ꢁHCl in 200 mL H2O was added in one portion.
The mixture was heated at reflux 1 h, was cooled to room tem-
perature and neutralized with anhydrous NaHCO3 . After 200
mL CH2Cl2 had been added and the layers separated, the aqu-
eous portion was extracted with three 100 mL portions of
CH2Cl2 . The combined organic layers were dried over
MgSO4 , filtered and solvent was removed by rotary evapora-
tion to leave a red-brown oil. The red–brown oil was trans-
ferred to a distillation apparatus fitted with a vigreaux
column. The 9.42 g (44% yield based on butyraldehyde diethyl-
acetal) of colorless to pale yellow liquid that distilled between
73–74 ꢂC/1 mmHg (Lit bp’s, 87–89 ꢂC/2 mmHg;7c 82–85 ꢂC/3
mmHg7d 104–105 ꢂC/3 mmHg;7e 98–100 ꢂC/5 mmHg;7f
122 ꢂC/16 mmHg7b) was pure H(pz4Et) as indicated by 1H
NMR spectroscopy. HRMS-Direct probe (m/z): calcd for
C5H8N2 , 96.0687 found, 96.0682. 1H NMR (300 MHz,
CDCl3) 9.86 (br s, 1H, NH), 7.42 (s, 2H, H3,5-pz), 2.54 (q,
J ¼ 7.8 Hz, 2 H, CH2CH3), 1.22 (t, J ¼ 7.8 Hz, 3 H,
13
CH2CH3). C NMR (75.4 MHz, CDCl3) 132.4 (br s, C N),
123.1 (C4-pz), 17.5 (CH2), 15.4 (CH3)
=
4-(Butyl)pyrazole. The product mixture from the Vilsmeier
formylation of 40.6 g (233 mmol) hexanaldehyde diethylacetal
with 46.9 mL POCl3 (78.6 g, 513 mmol) and 43.0 mL (40.9 g,
560 mmol) DMF, after hydrolysis and neutralization, was
extracted with four 100 mL portions of CH2Cl2 followed by
four 100 mL portions of Et2O. The combined organics were
dried over MgSO4 , filtered, and solvent was removed to leave
a red–brown oil. DMF was removed by vacuum distillation
and the distillation residue (31.3 g) was found to be a mixture
of 3-ethoxy-2-butyl-prop-2-enal and 3-(dimethylamino)-2-
butyl-prop-2-enal)] in a 1.21 : 1 mol ratio (201 mmol total,
86% based on hexanaldehyde diethylacetal). [Note: these pro-
Syntheses
(4-Ethyl)pyrazole. A 500 mL three-necked flask fitted with a
magnetic stir bar was connected to a pressure-equalizing addi-
tion funnel, a nitrogen inlet valve, the system was sealed with
rubber septa, and was purged by three alternating evacuations
and nitrogen backfills. A 45.6 mL (74.6 g, 486 mmol) portion
of POCl3 was added to the 500 mL flask by syringe and was
cooled to 0 ꢂC by an external ice water bath. Freshly distilled
(dry) DMF (50.1 mL, 47.1 g, 644 mmol) was added to the
addition funnel by syringe, then dropwise over the course of
30 min to the vigorously stirred POCl3 . During the addition,
ducts were separated in a repeated experiment; ethoxy deriva-
=
1
tive H NMR (300 MHz, CDCl3) 9.18 (s, HC O), 6.92 [s,
HC(OEt)], 4.16 (q, J ¼ 7.2 Hz, OCH2), 2.70 (t, J ¼ 5.4 Hz,
2H, CCH2), 2.20 (t, J ¼ 7.2 Hz, OCH2CH3), 1.40–1.27 (br
the Vilsmeier reagent, [Me2N CHCl ][PO2Cl2ꢀ], precipitated
+
=
as a colorless solid. Next, 32.5 g (222 mmol) of butyraldehyde
diethylacetal was added by syringe to the addition funnel, then
dropwise over the course of 30 min, to the suspension of the
Vilsmeier reagent. After the reaction mixture was warmed to
room temperature with an external water bath, the flask was
placed in a preheated oil bath (that was maintained between
70–80 ꢂC) for 2 h where the reaction mixture gradually chan-
ged color from yellow to orange to brown. The resulting
brown mixture was poured into 600 g crushed ice and was
allowed to stand overnight. Anhydrous potassium carbonate
(ca. 100 g) was carefully added in 5 g portions (to prevent over-
flow from effervescence) until the solution became basic and
370 mL of water was added to dissolve the precipitated salts.
The aqueous solution was sequentially extracted with CH2Cl2
(5 ꢃ 150 mL), benzene (5 ꢃ 150 mL), Et2O (3 ꢃ 100 mL), THF
(4 ꢃ 150 mL) and finally CHCl3 (3 ꢃ 150 mL) (see text), the
organic fractions combined and dried over MgSO4 , filtered,
and solvent was removed by rotary evaporation to leave a
red-brown oil. The red-brown oil was transferred to a distilla-
tion apparatus and the portion that distilled below ca. 55 ꢂC/1
mmHg (DMF) was discarded. The portion that distilled
between 65–70 ꢂC/1 mmHg (4.32 g, 33.7 mmol) was identified
as 3-ethoxy-2-ethyl-prop-2-enal by NMR 1H NMR (300 MHz,
m, 2H), 0.88 (t, J ¼ 8 Hz, CH3); dimethylamino derivative
1
=
H NMR (300 MHz, CDCl3) 8.75 (s, HC O), 6.76 [s,
HC(NMe2)], 3.18 (s, 6H, NMe2), 2.37 (m, 2H, CCH2), 1.36–
1.25 (br m, 4H, Bu), 0.90 (t, 3H, CH3).] The residue was
allowed to react with 14.4 g (210 mmol) NH2NH2ꢁHCl, as
above, neutralized, and extracted with four 150 mL portions
of CH2Cl2 . Fractional distillation at 97–99 ꢂC/1 mmHg (Lit8c
bp, 95–98 ꢂC/1.5 mmHg) afforded 18.8 g (65% based on hexa-
naldehyde diethylacetal) of (4-butyl)pyrazole as a colorless to
pale yellow liquid. HRMS- Direct probe (m/z): calcd for
C7H12N2 , 124.1000 found, 124.0996. 1H NMR (300 MHz,
CDCl3) 9.86 (br s, 1H, NH), 7.41 (s, 2H, H3,5-pz), 2.50 (t,
J ¼ 7.8 Hz,
2 H, CH2CH2CH2CH3), 1.56 (m, 2 H,
CH2CH2CH2CH3), 1.37 (m, 2 H, CH2CH2CH2CH3), 0.93
(m, 3 H, CH2CH2CH2CH3). 13C NMR (75.4 MHz, CDCl3)
=
132.9 (br s, C N), 121.5 (C4-pz), 33.3 (CH2), 23.9 (CH2),
22.5 (CH2), 14.1 (CH3).
4-(Pentyl)pyrazole. The product mixture from the Vilsmeier
formylation of 43.1 g (229 mmol) heptanaldehyde diethylace-
tal, 46.0 mL (77.1 g, 503 mmol) POCl3 , and 42.0 mL (40.1 g,
0.55 mol) DMF after hydrolysis was extracted with four 150
mL portions CH2Cl2 and two 150 mL portions of diethyl
=
CDCl3) 9.18 (s, 1H, HC O), 6.89 (s, 1H, HC(OEt)), 4.16 (q,
1674
New J. Chem., 2003, 27, 1670–1677

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fractions that distilled between 120–140 ꢂC under vacuum
(1 mmHg). HRMS-Direct probe (m/z): calcd for C10H18N2 ,
166.1470 found, 166.1472. H NMR (300 MHz, CDCl3) 7.39
(s 2H, H3,5-pz), 7.10 (br s, 1H, NH), 2.45 (m, 1H, CH(Et)Bu),
1.62 (m, 2H, CH2), 1.49 (m, 2H, CH2), 1.35–1.15 (br, m, 4H,
ether. The aqueous fraction was neutralized by adding 140 g
(1.01 mol) anhydrous K2CO3 in 5 g portions to prevent over-
flow from effervescence, then was extracted with an additional
two 100 mL portions of CH2Cl2 followed by two 100 mL
portions of Et2O. After drying the combined organics over
MgSO4 , filtering, and removing solvents by rotary evapora-
tion, 9.62 g (132 mmol) of DMF was removed by vacuum
distillation at 35–45 ꢂC/1 mmHg. The residue 32.0 g was a
mixture of 3-ethoxy-2-pentylprop-2-enal and 3-(dimethyl-
amino)-2-pentylprop-2-enal in a 2 : 3 mol ratio as indicated
by NMR (188 mmol total, 82% based on heptanaldehyde
diethylacetal). [Note: these products were separated in a
repeated experiment; ethoxy derivative 1H NMR (300 MHz,
1
CH2), 0.86 (t, J ¼ 7 Hz, 3H, CH3), 0.82 (t, J ¼ 8 Hz, 3H,
13
CH3). C NMR (CDCl3) 132.4 (br s, -C N), 125.6 (C4-pz),
37.3, 36.2, 29.8, 29.7, 23.0, 14.3, 12.0.
=
4-(Cyclohexyl)pyrazole. The product mixture from the Vils-
meier formylation of 8.07 g (44.4 mmol) 2,20-diethoxyethyl-
cyclohexane, 8.10 mL POCl3 (13.6 g, 88.5 mmol) and 6.88
mL (6.49 g, 88.8 mmol) DMF, after hydrolysis, neutralization,
and extraction with three 100 mL portions CH2Cl2 , one 100
mL portion C6H6 , one 100 mL portion Et2O followed by
another two 100 mL portions CH2Cl2 afforded 6.20 g of a mix-
ture of the ethoxy acrolein and dimethylamino acrolein in a
4.26:1 mol ratio (34.1 mmol, 78% based on 2,20-diethoxyethyl-
cyclohexane). [1H NMR (400 MHz, CDCl3) of unseparated
mixture had resonances for ethoxy derivative at dH 9.27, 9.09
=
CDCl3) 9.16 (s, HC O), 6.92 [s, HC(OEt)], 4.14 (q, J ¼ 7.2
Hz, OCH2), 2.67 (t, J ¼ 5.4 Hz, 2H, CCH2), 2.17 (t, J ¼ 7.2
Hz, OCH2CH3), 1.43–1.30 (br m, 6H), 0.88 (t, J ¼ 8 Hz,
3H, CH3); dimethylamino derivative 1H NMR (300 MHz,
=
CDCl3) 8.53 (s, HC O), 7.63 [s, HC(NMe2)], 3.33 (s, 6 H,
NMe2), 2.38 (m, 2H, CCH2), 1.43–1.30 (br m, 4H), 0.88 (t,
J ¼ 8 Hz, CH3)]. The distillation residue was allowed to react
with 15.6 g (228 mmol) NH2NH2ꢁHCl as above. The red–
brown oil obtained after neutralization and extraction was
transferred to a short path distillation apparatus. The yellow
liquid that distilled between 125–127 ꢂC/1 mmHg was pure
(4-pentyl)pyrazole as indicated by NMR (18.5 g, 133.7 mmol,
58.4% based on heptanaldehyde diethylacetal). This com-
pound crystallized on standing overnight in a refrigerator.
Mp, ca. 21–23 ꢂC. HRMS- Direct probe (m/z): calcd for
C8H14N2 , 138.1157 found, 138.1155. 1H NMR (400 MHz,
CDCl3) 8.02 (br s, 1H, NH), 7.41 (s 2H, H3,5-pz), 2.49 (t,
J ¼ 8 Hz, 2H, CH2), 1.58 (pseudoquint, 2H, CH2), 1.33 (m,
4H, CH2), 0.90 (t, J ¼ 8 Hz, CH3). 13C NMR (CDCl3) 132.9
=
(s, HC O), 6.89 [s, HC(OEt)], 4.48, 4.14 (q, J ¼ 7.2 Hz, 2H,
OCH2CH3), 2.56 (m, 1H, CH), 1.80–1.60 (m 2H), 1.50–1.35
(m, 2H), 1.37 (t, J ¼ 7.2 Hz, 3H OCH2CH3) 1.31–1.12 (br
m, CH2), 0.90–0.77 (br m, CH2) along with resonances for
=
the dimethylamino derivative at dH 8.62, 7.88 (s, HC O),
7.00 [s, HC(NMe2)], 3.88, 3.47, 3.14 (s, NMe2).] After dissol-
ving the mixture in 10 mL MeOH and allowing the mixture
to react with 2.33 g (25 mmol) N2H4ꢁHCl in 25 mL H2O, fol-
lowed by standard workup, the crude red oil (3.98 g) was
transferred to a 100 mL Schlenk flask which was subsequently
connected to another 100 mL Schlenk flask by a glass elbow,
the flask containing the residue was evacuated (0.1 mmHg)
and heated to ca. 230 ꢂC. The crude pyrazole sublimed into
the glass elbow and was washed with hexanes to remove
trace highly-colored impurities. The washings were cooled to
ꢀ20 ꢂC overnight to give 0.52 g of the desired pyrazole as
pale yellow needles after filtering from the mother liquor and
drying under vacuum. The combined yield of (4-cyclohexyl)-
pyrazole as a colorless powder (the original hexane insoluble
solid) and as the recovered crystalline solid was 2.90 g (47%
based on 2,20-diethoxyethylcyclohexane). Mp: 128–130 ꢂC
(Lit.9e 130 ꢂC). Anal. Calcd. For C9H14N2 : C, 71.96 (71.64)
=
(br s, -C N), 121.6 (C4-pz), 31.7 (CH2), 30.8 (CH2), 24.2
(CH2), 22.7 (CH2), 14.3 (CH3).
Alternatively, 4-pentylpyrazole may be more easily handled
as its hydrogen chloride salt (prepared independently with aqu-
eous HCl solution and Et2O in the above preparation). Color-
less crystals of [H2pz][Cl] in two morphologies (needles as the
major form and blocks as the minor component) are produced
by layering an Et2O solution with hexanes and by allowing the
layers to diffuse. See ESIz for crystal structures. Mp: 127–
128 ꢂC. (Lit.8b mp 127–128.5 ꢂC) Anal. Calcd. (Obs.) For
C8H15N2Cl: C, 55.01 (55.40); H, 8.66 (8.28); N, 16.04
(16.21). 1H NMR (400 MHz, CDCl3) d. 13.98 (br s, 2H,
NH), 7.73 (s 2H, H3,5-pz), 2.56 (t, J ¼ 8 Hz, 2H, CH2), 1.60
1
H, 9.39 (9.04) N, 18.65 (18.42). H NMR (300 MHz, CDCl3)
7.56 (br s, 1H, NH), 7.42 (s 2H, H3,5-pz), 2.53 (m, 1H, C1H-
cy), 1.92 (m, 2H, CH2), 1.81–1.70 (br, m, 3H), 1.44–1.17 (br
=
13
m, 5H). C NMR (75.4 MHz, CDCl3) 131.5 (br s, -C N),
(pseudoquint, 2H, CH2), 1.31 (m, 4H, CH2), 0.89 (t, J ¼ 8
13
=
=
127.9 (-C ), 34.7, 34.1 (C1), 26.6, 26.3.
Hz, CH3). C NMR (CDCl3) d 130.8 (br s, -C N), 123.5
(C4-pz), 31.2 (CH2), 30.0 (CH2), 23.7 (CH2), 22.5 (CH2),
14.1 (CH3).
4-(Phenyl)pyrazole. The product mixture of the Vilsmeier
reaction between 5.20 mL POCl3 (8.71 g, 56.8 mmol), 4.60
mL (4.34 g, 59.4 mmol) DMF, and 5.04 g (25.9 mmol) pheny-
lacetaldehyde diethylacetal was hydrolyzed and neutralized as
described for the ethyl derivative. Extraction with six 100 mL
portions of CH2Cl2 and removal of solvents (including DMF)
left 2.00 g of a solid residue thought to be the dimethylamino
acrolein (11.4 mmol, 44.0% based on phenylacetaldehyde
diethylacetal) due to the lack of ethoxy resonances in its com-
rac-4-[(a-Ethyl)pentyl]pyrazole. The product mixture from
the Vilsmeier formylation of 9.00 g (41.6 mmol) (3-ethyl)hep-
tanaldehyde diethylacetal with 8.40 mL POCl3 (14.1 g, 91.8
mmol) and 7.80 mL (7.36 g, 101 mmol) DMF after hydrolysis
and extraction with six portions of CH2Cl2 followed by three
100 mL portions Et2O, afforded 4.71 g of a mixture of the
ethoxy acrolein and dimethylamino acrolein in a 1.7 : 1 mol
ratio (23.8 mmol, 57.1% based on (3-ethyl)heptanaldehyde
diethylacetal). [1H NMR (400 MHz, CDCl3) of unseparated
mixture had resonances for ethoxy derivative at dH 9.16 (s,
1
plicated NMR spectrum. H NMR (400 MHz, CDCl3) 10.5,
9.78, 9.66, 9.06, 8.66, 8.01, 7.80, 7.56–7.17 (br m), 6.93 (br
m), 3.86–2.60 (br). The residue was dissolved in 10 mL MeOH
and was treated with 0.78 (11.4 mmol) N2H4ꢁHCl in 25 mL
H2O. Following workup, a red black solid remained and was
subjected to purification as described for (4-cyclohexyl)pyra-
zole affording 1.36 g of (4-phenyl)pyrazole as a colorless solid
(36.4% based on phenylacetaldehyde diethylacetal). Mp: 234–
235 ꢂC (Lit mp’s; 236–237 ꢂC,10b and others between 228–
232 ꢂC.7d,10a,10d–h) Anal. Calcd. for C9H8N2 : C, 74.98 (74.98)
H, 5.59 (5.50) N, 19.43 (19.36). 1H NMR (300 MHz, acet-
one-d6) 12.21 (br, s, 1H, NH), 8.01 (s, 2H, H3,5-pz), 7.61 (d,
J ¼ 7.5 Hz, 2H, o-Ph), 7.35 (dd, J ¼ 7.5, 1 Hz, 2H, m-Ph),
=
HC O), 6.89 [s, HC(OEt)], 4.14 (q, J ¼ 7.2 Hz, OCH2), 2.58
(m, 1H, CH), 1.62 (m 2H), 1.50 (m, 2H), 1.38 (t, J ¼ 7.2 Hz,
3H OCH2CH3) 1.29–1.12 (br m, 2H), 0.92–0.77 (br m, CH3)
along with resonances for the dimethylamino derivative at
=
dH 8.23 (s, HC O), 6.76 [s, HC(NMe2)], 3.11 (s, NMe2).] After
dissolving the mixture in 10 mL MeOH and allowing the mix-
ture to react with 1.7 g (25 mmol) N2H4ꢁHCl in 25 mL H2O,
followed by standard workup, a 3.5 g (51% based on (3-ethyl)-
heptanaldehyde diethylacetal) of rac-[4-(a-ethyl)pentyl]pyra-
zole as a pale yellow liquid was isolated by collecting the
New J. Chem., 2003, 27, 1670–1677
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(-CH2CH3), 15.1 (CH3). Samples for X-ray structural studies
were grown similarly, however, since the crystals decompose
readily in the absence of solvent, the mother liquor was
retained and the crystals were mounted as described below.
(dt, J ¼ 7.5, 1 Hz, 1 H, p-Ph). 13C NMR (75.4 MHz CDCl3)
136.5, 134.2, 129.6, 126.8, 126.2, 125.9, 122.8.
1,10,3,30-Tetrakis[(4-ethyl)pyrazol-1-yl]propane,
CH2[CH-
(pz4Et)2]2. A 10 mL Schlenk tube fitted with a magnetic stirbar
was charged with 0.43 mL (0.43 g, 0.026 mol) malonaldehyde
dimethylacetal, 1.0 g (0.10 mol) of (4-ethyl)pyrazole, and
0.050 g (0.26 mmol) p-toluenesulfonic acid monohydrate.
The flask was attached to a reflux condenser and heated 10 h
with an oil bath maintained at 180ꢂ (caution, an oil bath at this
temperature must be located in a hood and can ignite). The
sample was periodically cooled and the progress of the reaction
was monitored by 1H NMR spectroscopy which indicated 90%
conversion during the heating period. After that time, the reac-
tion mixture was worked up by transferring the contents of the
Schlenk tube to a separatory funnel with CH2Cl2 , the organic
layer was washed with water and was separated. The aqueous
portion was then extracted with three 50 mL portions of
CH2Cl2 , the combined organic fractions were dried over
MgSO4 , filtered and solvent was removed to leave a brown
oil. Column chromatography on silica gel with Et2O as the elu-
ent afforded 0.66 g (60% yield based on malonaldehyde
dimethylacetal) of CH2[CH(pz4Et)2]2 as a pale yellow-brown
viscous liquid in the first yellow band. HRMS-direct probe
(m/z): calcd for C23H32N8 : 420.2750 found, 420.2740. Direct
probe MS m/z (Rel. Int.%) [assgn]: 420 (9) [M]+, 325 (26)
[M-pz4Et]+, 229 (77) [M-2 pz4Et -H]+, 204 (100) [HC(pz4Et)2]+,
133 (42) [M-3H pz4Et]+. 1H NMR (400 MHz, CDCl3) 7.39
(s, 4H, H5-pz), 7.30 (s, 4H, H3-pz), 6.00 (t, J ¼ 8 Hz, 2H,
CH(pz)2), 3.80 (t, J ¼ 8 Hz, 2H, CH2), 2.44 (q, J ¼ 8 Hz,
8H, CH2CH3), 1.16 (t, J ¼ 8 Hz, 12 H, -CH3). 1H NMR
(400 MHz, acetone-d6) 7.55 (s, 4 H, H3-pz), 7.37 (s 4H, H5-
pz), 6.08 (t, J ¼ 8 Hz, 2H, CH(pz)2), 3.86 (t, J ¼ 8 Hz, 2H,
CH2), 2.44 (q, J ¼ 8 Hz, 8H, CH2CH3), 1.14 (t, J ¼ 8 Hz,
12 H, -CH3). 13C NMR (101.62 MHz, CDCl3) 140.1 (C5-pz),
126.1 (C3-pz), 124.8 (C4-pz), 72.0 (CH-pz), 38.1 (CH2), 17.6
(–CH2CH3), 15.0 (CH3). 13C NMR (101.62 MHz, acetone-
d6) 140.0 (C5-pz), 127.3 (C3-pz), 125.0 (C4-pz), 72.6 (CH-pz),
38.1 (CH2), 17.9 (–CH2CH3), 15.3 (CH3).
Crystal structure determinations
H(pz4Ph). A brown needle bar crystal of H(pz4Ph) was
mounted onto the end of a thin glass fiber using inert oil. X-
ray intensity data were measured at 150.0(2) K on a Bruker
SMART APEX CCD-based diffractometer (Mo Ka radiation,
21
˚
l ¼ 0.71073 A). The raw data frames were integrated with
SAINT+,21 which also applied corrections for Lorentz and
polarization effects. The final unit cell parameters are based
on the least-squares refinement of 4205 reflections from the
data set with I > 5s(I). Analysis of the data showed negligible
crystal decay during data collection. No correction for absorp-
tion was applied.
Systematic absences in the intensity data uniquely deter-
mined the space group Pbcn. The structure was solved by a
combination of direct methods and difference Fourier synth-
eses, and refined against F2 by full-matrix least-squares, using
SHELXTL.22 After identification and anisotropic refinement
of all non-hydrogen atoms, hydrogen atoms attached to
appropriate carbon atoms were clearly located in the difference
map and freely refined with isotropic displacement parameters.
At this point apparent hydrogen positions (H1N and H2N) for
both nitrogens were observed, in violation of electroneutrality.
This corresponds to equal disorder of one hydrogen over both
nitrogens. Refinement of the occupancies of H1N and H2N
1
2
resulted in reasonable Ueq values and occupancies close to
for each H atom. For the final refinement cycles the occupan-
cies of H1N and H2N were fixed at 12, and their xyz coordinates
and Ueq was allowed to refine freely.
Crystal data for C9H8N2 , M ¼ 144.17, orthorhombic, Pbcn,
˚
˚
˚
a ¼ 17.2047(11) A, b ¼ 11.8608(8) A, c ¼ 7.3253(5) A, U ¼
3
1494.81(17) A , Z ¼ 8, m(Mo-Ka) ¼ 0.079 mmꢀ1, T ¼ 150(2).
˚
8275 reflections measured, 1191 unique (Rint ¼ 0.0525), 137
parameters. Final R1 [I > 2(I)] ¼ 0.0354, wR2 [all data] ¼
0.0860, GoF ¼ 1.055.
[Ag2{l-CH2[CH(pz4Et)2]2}2]3[Ag(NO3)4]2 (1). A solution of
0.11 g (0.62 mmol) Ag(NO3) in 10 mL CH3CN was added
by cannula to a foil-covered 50 mL Schlenk flask that con-
tained a solution of 0.26 g (0.62 mmol) CH2[CH(pz4Et)2]2 in
10 mL CH3CN. After the resulting tea-colored solution had
been magnetically stirred for 2 h at room temperature, the sol-
vent was removed by vacuum distillation, the residue was
washed with two 5 mL portions of Et2O, dried under vacuum
to leave a pale tan solid. The solid was then dissolved in a mini-
mal amount (5 mL) of acetone, filtered into a vial for crystal-
lization, and layered with Et2O. Colorless crystals formed
while allowing the solvents to diffuse overnight. The mother
liquor was removed by pipette and the resulting crystals were
dried under vacuum for 1 h to leave 0.25 g of analytically pure
1 (84% based on CH2[CH(pz4Et)2]2) as opaque blocks. Mp
125–130 ꢂC decomp. pale yellow glass; 145–150 ꢂC apparent
gas evolution, 160 ꢂC liquifies. Anal. Calcd. (found) for
[Ag2{l-CH2[CH(pz4Et)2]2}2]3[Ag(NO3)4]2 (1). Large well-
formed colorless block crystals of [Ag2{m-CH2[CH-
(pz4Et)2]2}2]3[Ag(NO3)4]2 (1) are stable when left undisturbed
in the mother liquor, but are extremely sensitive to tempera-
ture changes and mechanical manipulation. Crystals survive
for several seconds in paratone-N oil, long enough for quick
mounting and flash-freezing on the diffractometer, but crack
immediately when placed in the diffractometer cold stream.
After a series of unsuccessful attempts at temperatures ranging
from 240 K to 100 K, low-temperature data collection was
abandoned and crystals were mounted in the mother liquor
inside thin-walled capillary tubes. Complete (sphere) data sets
for three crystals were collected (Bruker SMART APEX dif-
˚
fractometer, Mo Ka, l ¼ 0.71073 A; raw data frame integra-
tion with SAINT+).21 All three crystals showed significant
cracking during the < 8 h data collections, and only the best
of these data sets is reported here. Due to the crystal stability
problems, only general features of the connectivity and mole-
cular geometry will be reported; bond lengths and angles
should be considered imprecise and unreliable. The crystal
instability is most likely due to the high disordered solvent con-
tent (ca. 45% of the total unit cell volume, calculated by PLA-
TON23), which is also responsible for the lack of appreciable
X-ray scattering above ca. 2y ¼ 40ꢂ.
C138H192N56O24Ag8 : C, 42.69 (42.22); H, 4.98 (4.72); N,
20.20 (19.84). ESI(+) MS m/z (Rel. Int.%) [assgn]: 1305 (0.3)
[Ag2L2(NO3)2(H2O)]+, 1287 (0.5) [Ag3L2(NO3)2]+, 1118 (10)
[Ag3L2(NO3)]+, 949 (87) [AgL2]+, 568 (40) [AgL(CH3CN)]+,
527 (40) [AgL]+, 421 (22) [L]+, 325 (100) [L-pz4Et]+. ESI(ꢀ)
MS m/z (Rel. Int.%) [assgn]: 1411 (9) {[Ag2L2][Ag(NO3)4]}ꢀ,
991 (8) {[Ag2L][Ag(NO3)4]}ꢀ, 822 (15) [Ag2L(NO3)3]ꢀ, 402
(100) [Ag2(NO3)3]ꢀ, 231 (70) [Ag(NO3)2]ꢀ. 1H NMR (400
MHz, acetone-d6) 7.92 (s, 4H, H3-pz), 7.63 (t, J ¼ 8 Hz, 2H,
CH(pz)2), 7.53 (s, 4H, H5-pz), 4.48 (t, J ¼ 8 Hz, 2H, CH2),
2.46 (q, J ¼ 8 Hz, 8H, CH2CH3), 1.16 (t, J ¼ 8 Hz, 12 H,
-CH3). 13C NMR (101.62 MHz, acetone-d6) 143.0 (C5-pz),
131.1 (C3-pz), 124.6 (C4-pz), 71.6 (CHpz), 38.5 (CH2), 17.7
Compound 1 crystallizes in the triclinic system, in the space
¯
group P1. The asymmetric unit contains half each of three
[Ag2(m-C23H32N8)2]2+ cations and one [Ag(NO3)4]3ꢀ anion.
All ethyl groups of the cations show inflated displacement
ellipsoids, a symptom of disorder. Two terminal –CH3 groups
1676
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Inorg. Chem., 2001, 40, 1508; (c) D. L. Reger, T. C. Grattan,
K. J. Brown, C. A. Little, J. J. S. Lamba, A. L. Rheingold and
R. D. Sommer, J. Organomet.Chem., 2000, 607, 120.
4-Ethyl pyrazole: (a) T. V. Protopopova, V. T. Klimko and A. P.
Skoldinov, Khim. Nauk. Prom., 1959, 4, 805; (b) H. Bredereck,
H. Herlinger and E. H. Schweizer, Chem. Ber., 1960, 93, 1208;
(c) L. A. Yanovskaya and V. F. Kucherov, Izv. Akad. Nauk,
SSSR, Ser. Khim., 1960, 2184; (d ) V. T. Klimko, T. V.
Protopopova and A. P. Skoldinov, Zh. Obsch. Khim., 1961, 31,
170; (e) C. Alberti and G. Zerbi, Farm. Ed. Sci., 1961, 16, 527;
( f ) I. F. Revinskii, I. G. Tishchenko and P. Nahar, Vestn.
Belorus. Un-ta, Ser. 2, 1982, 2, 75; (g) B. R. Tolf, R. Dahlbom,
A. Akeson and H. Theorell, Biol. Act. Princ. Nat. Prod., eds.
W. Voelter and D. G. Daves, 1984, 265.
of the ethyl substituents could not be located due to disorder
[the affected ethyl groups are associated with pz rings N(61)–
C(63) (Ag2) and N(111)–C(113) (Ag3)]. All located species
were refined anisotropically with hydrogens in idealized posi-
tions. Multiple diffusely distributed electron density peaks
are also present in voids between the identifiable species,
assumed to be disordered solvent. These were modeled as vari-
able occupancy carbon atoms with a common fixed isotropic
displacement parameter. Solvent peaks were assigned until
the largest residual electron density was located near an Ag
atom. SHELXTL22 and PLATON23 were used to perform
the calculations.
7
8
9
4-Propyl and longer straight-chain pyrazole analogues: (a) Y. M.
Batulin, V. T. Klimko, T. A. Klygul, N. E. Chupriyanova, Y. I.
Vikhlyaev and A. P. Skoldinov, Khim. Farm. Z., 1968, 2(2), 3;
(b) R. Dahlbom, B. R. Tolf, A. Akeson and H. Theorell,
Biochem. Biophys. Res. Commun., 1974, 57(3), 549; (c) B. R. Tolf,
J. Piechaczek, R. Dahlbom, H. Theorell, A. Akeson and
G. Lundquist, Acta Chem. Scand., Ser. B, 1979, B33(7), 483.
Branched and cyclic 4-alkyls: (a) C. Botteghi, L. Lardici, E.
Benedetti and P. Pino, Chim. Ind., 1967, 49(2), 171; (b) L.
Lardicci, C. Botteghi and P. Salvadori, Gazz. Chim. Ital., 1968,
98(6), 760; (c) C. Botteghi, E. Guetti, G. Ceccarelli and L.
Lardicci, Gazz. Chim. Ital., 1972, 102(11), 945; (d ) see ref. 4c
(4-amyl) and 5a (iso-Pr); (e) C. Reichardt, A. R. Ferwanah, W.
Pressler and K. Y. Yu, Liebigs Ann. Chem., 1984, 4, 649; ( f ) see
ref. 5c for cyclohexyl; (g) A. L. Rheingold, L. M. Liable-Sands,
J. L. Golan and S. Trofimenko, Eur. J. Inorg. Chem., 2003, 2767.
Crystal data for C138H192Ag8N56O24 , M ¼ 3882.44, triclinic,
˚
˚
˚
¯
P1, a ¼ 12.2524(7) A, b ¼ 21.8178(13) A, c ¼ 27.0779(16) A,
a ¼ 68.5730(10)ꢂ, b ¼ 80.9340(10)ꢂ, g ¼ 87.3490(10)ꢂ, U ¼
3
6653.5(7) A , Z ¼ 1, m(Mo-Ka) ¼ 0.626 mmꢀ1, T ¼ 293(2).
˚
31 940 reflections measured, 14 793 unique (Rint ¼ 0.0387),
1079 parameters. Final R1 [I > 2(I)] ¼ 0.0727, wR2 [all
data] ¼ 0.2481, GoF ¼ 1.037.
Acknowledgements
We thank the National Science Foundation (CHE-0110493)
for support. The Bruker CCD Single Crystal Diffractometer
was purchased using funds provided by the NSF Instrumen-
tation for Materials Research Program through Grant
DMR:9975623.
10 4-Phenyl(a) W. Kirmse and L. Horner, Justus Liebigs Ann. Chem,
1958, 614, 1; (b) E. Klingsberg, J. Am. Chem. Soc., 1961, 83, 2934;
(c) see Ref. 4d; (d ) H. Pluempe and E. Schegk, Archiv. Pharm.
Ber. Deutsch. Pharm. Ges., 1967, 300(8), 704; (e) I. El-Sayed
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Sanchez, Tetrahedron Lett., 1988, 29(46), 6001; (i) S. M. Allin,
W. R. S. Barton, W. R. Bowman and T. McInally, Tetrahedron
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11 H. V. Hansen, J. A. Caputo and R. I. Meltzer, J. Org. Chem.,
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12 K. C. Brannock, J. Org. Chem., 1960, 25, 258.
13 (a) Z. Arnold and J. Zemlicka, Chem. Listy pro Vedu a Prumsyl,
1952, 52, 458; (b) Z. Arnold and F. Sorm, Collect. Czech Chem.
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E. Breitmailer, Synthesis, 1983, 641.
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1677