1,3-Dipolar cycloaddition in the synthesis of pyrazolyl-substituted nitronyl nitroxides

Article abstract of DOI:10.1007/s11172-006-0093-6

A new approach to the synthesis of polyfunctional pyrazolyl-substituted nitronyl nitroxides was developed based on the presynthesized pyrazole derivatives prepared by 1,3-dipolar cycloaddition. The structures of the resulting mono- and biradicals were confirmed by X-ray diffraction.

Full text of DOI:10.1007/s11172-006-0093-6

Russian Chemical Bulletin, International Edition, Vol. 54, No. 9, pp. 2169—2181, September, 2005
2169
1,3ꢀDipolar cycloaddition in the synthesis of
pyrazolylꢀsubstituted nitronyl nitroxides*
E. V. Tretyakov,a S. E. Tolstikov,b G. V. Romanenko,a Yu. G. Shvedenkov,a R. Z. Sagdeev,a and V. I. Ovcharenkoa,b
ꢀ
aInternational Tomography Center, Siberian Branch of the Russian Academy of Sciences,
3a ul. Institutskaya, 630090 Novosibirsk, Russian Federation
Fax: +7 (383 3) 33 1399. Eꢀmail: Victor.Ovcharenko@tomo.nsc.ru
bNovosibirsk State University,
2 ul. Pirogova, 630090 Novosibirsk, Russian Federation
A new approach to the synthesis of polyfunctional pyrazolylꢀsubstituted nitronyl nitroxides
was developed based on the presynthesized pyrazole derivatives prepared by 1,3ꢀdipolar cycloꢀ
addition. The structures of the resulting monoꢀ and biradicals were confirmed by Xꢀray difꢀ
fraction.
Key words: nitronyl nitroxide radicals, 1,3ꢀdipolar cycloaddition, pyrazole, Xꢀray diffracꢀ
tion analysis.
Scheme 1
The complexes of Cu(hfac)2 with 2ꢀ(1ꢀalkylꢀ1Hꢀ
pyrazolꢀ4ꢀyl)ꢀ4,4,5,5ꢀtetramethylꢀ4,5ꢀdihydroꢀ1Hꢀimidꢀ
azoleꢀ1ꢀoxyl 3ꢀoxide (1) have a unique ability to undergo
specific magneticꢀstructural phase transitions, which are
manifested in the temperature dependence of the effecꢀ
tive magnetic moment (µeff) as anomalies similar in charꢀ
acter to spin transitions. This ability has attracted great
interest1,2 and stimulated the development of the chemisꢀ
try of spinꢀlabeled pyrazoles.3 The synthesis of "symmetriꢀ
cal" (with respect to donor groups) nitroxides, which can
serve as parent compounds of pyrazoleꢀsubstituted monoꢀ
and bisꢀnitronyl nitroxides, has attracted our attention.
A known approach4,5 to the synthesis of mononitroxides 1
involves Nꢀalkylation of pyrazole followed by formylation
of the resulting Nꢀalkylpyrazole, condensation of Nꢀalkylꢀ
pyrazoleꢀ4ꢀcarbaldehyde with 2,3ꢀbis(hydroxyamino)ꢀ
2,3ꢀdimethylbutane sulfate (2•H2SO4•H2O), and oxidaꢀ
tion of 1,3ꢀdihydroxyimidazolidine to form nitronyl
nitroxide (Scheme 1).
A weak point of the synthetic sequence is that formylaꢀ
tion is characterized by an unstable yield (20—60%). In
addition, the severe conditions of this step (POCl3,
130—150 °C) substantially limit the possibility of the synꢀ
thesis of pyrazolylꢀsubstituted nitronyl nitroxides and
imino nitroxides. This stimulated us to develop an effiꢀ
cient procedure for the synthesis of Nꢀunsubstituted spinꢀ
labeled pyrazole 1a (R = H), because the presence of a
reliable and easily scalable method for the preparation of
this compound opens wide possibilities for the synthesis
of paramagnetic pyrazole derivatives, including Nꢀfuncꢀ
R = Me, Et, Pr, Pri, Bu
tionalization of the pyrazole ring. When solving this probꢀ
lem, we rejected the classical method6 based on the use of
pyrazoleꢀ4ꢀcarbaldehyde, which is difficult to synthesize,7
and examined the possibility of using 1,3ꢀdipolar cycloadꢀ
dition of diazomethane to propiolaldehyde acetal as the
initial step. In the present study, we demonstrated that
* Dedicated to Academician A. L. Buchachenko on the occaꢀ
sion of his 70th birthday.
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 9, pp. 2105—2116, September, 2005.
1066ꢀ5285/05/5409ꢀ2169 © 2005 Springer Science+Business Media, Inc.

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Tretyakov et al.
this approach allows one to prepare the previously inꢀ
accessible polyfunctional mononitroxides 3a—c and
bis(nitronyl nitroxide) 4.
perform the reaction of diazomethane with 3,3ꢀdiethoxyꢀ
propyne (5) (Scheme 3). At room temperature, the reacꢀ
tion in Et2O in the presence of a rather large excess of
CH2=N2 is completed within several days. It is important
that subsequent methylation of pyrazole with diazoꢀ
methane under these conditions occurs much more slowly
(according to the TLC data, the final product contained
an insignificant amount of 1b, where R = Me). The reacꢀ
tion afforded a viscous oily product, which was a comꢀ
plex mixture (1H NMR data) containing predominantly
acetals 6 and 7. Attempts to separate a mixture of acetals
or isolate pyrazoleꢀ4ꢀcarbaldehyde from the hydrolysis
product of the mixture failed. Because of this, the visꢀ
cous oily product was subjected to condensation with
2•H2SO4•H2O with the aim of obtaining a mixture of
isomeric 1,3ꢀdihydroxyimidazolidines 8 and 9, which were
oxidized with NaIO4 without isolation. The resulting mixꢀ
ture can be separated by chromatography, and nitroxides
1a and 3a can be rather easily isolated from this mixture
(see Scheme 3). This procedure for the synthesis is reliꢀ
able, easily scalable, and allows the preparation of nitrꢀ
oxides 1a and 3a in 25 and 6% yields, respectively, based
on the starting 5 (see Scheme 3). This reaction also afꢀ
fords other products in small amounts. One of these prodꢀ
ucts is imino nitroxide 10, whose formation was conꢀ
firmed by a comparison with an authentic sample preꢀ
pared by reduction of 3a.
It should also be noted that we succeeded in growing
highꢀquality single crystals of nitroxides 1a, 3a, and 10
and established their molecular and crystal structures.
Since compound 1a is readily available, it was used as the
starting reagent for the preparation of new nitroxides 1
(Scheme 4) and, primarily, for the synthesis of sufficient
amounts of isotopically substituted compounds 1c,d
(R = CD3 and C2D5, respectively). The molecular strucꢀ
tures of 1c,d are shown in Fig. 1. The structural paramꢀ
eters are given in the Experimental section. These nitrꢀ
oxides were used in the synthesis of heterospin complexes,
which can show specific thermally induced spin transiꢀ
tions, and in the detailed analysis of magnetic anomalies
inherent in the nature of these complexes.1 The above
example shows that the possibility of alkylation of 1a comꢀ
bined with the aboveꢀdescribed procedure for its preparaꢀ
tion extends the scope of the synthesis of the desired
nitroxides necessary for the subsequent design of highꢀ
dimensional heterospin systems.
1: R = H (a), Me (b)
3: R1 = R2 = H (a), R1 = R2 = COOEt (b), R1 = COOEt, R2 = H (c)
Results and Discussion
The synthetic scheme used in the present study inꢀ
volves 1,3ꢀdipolar cycloaddition of the diazo compound
R1—CH=N2 to the corresponding alkyne R2—C≡C—R3
(Scheme 2). The resulting pyrazole derivatives can be
transformed into the target nitroxides.
Scheme 2
Cycloaddition is known to afford predominantly
3(5)ꢀsubstituted pyrazoles8 if a substituent in alkyne exꢀ
erts the –M effect. This fact is confirmed by the reaction
of CH2=N2 with HC≡C—CHO giving rise to pyrazoleꢀ
3(5)ꢀcarbaldehyde.9 Hence, the synthesis of pyrazoleꢀ4ꢀ
carbaldehyde, which is a precursor of 1a (R = H), reꢀ
quired that the reaction of CH2=N2 be performed with
alkyne containing such a synthetic equivalent of carbꢀ
aldehyde that, upon cycloaddition, will find itself at posiꢀ
tion 4 of the pyrazole ring. It should be noted that the
pathway of this reaction with alkynes bearing –I,+M or
–I substituents is difficult to predict.10,11 Nevertheless,
the absence of the ability of the substituent to exert a
mesomeric effect and an increase in the volume of the
substituent would be expected to be favorable for the forꢀ
mation of 4ꢀsubstituted pyrazoles. Hence, we decided to
We used alkynes 11a—c and 2,2ꢀdimethoxyꢀ1ꢀdiazoꢀ
ethane as substrates for the formation of formylpyrazoles,
which are required for the preparation of nitroxides 3
and 4. This approach allows one to rather easily prepare
aldehyde acetal 12a, from which nitroxide biradical 4 was
synthesized (see below). Based on this method, we develꢀ
oped approaches to the synthesis of formylpyrazoleꢀ
carboxylates 13 with the desired arrangement of funcꢀ
tional groups (Scheme 5).

Pyrazolylꢀsubstituted nitronyl nitroxides
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 9, September, 2005
2171
Scheme 3
Condensation of aldehydes 13a,b with 2,3ꢀbishydroxyꢀ
aminoꢀ2,3ꢀdimethylbutane (2) in MeOH affords 1,3ꢀdiꢀ
hydroxyimidazolidines 14a,b, which are oxidized with
NaIO4 in a twoꢀphase CHCl3—water system to give radiꢀ
cals 3b,c (see Scheme 5). Nitronyl nitroxide 3b is an oil.
However, we succeeded in growing single crystals of
hydroxyamine precursor 14a and determined its structure
(Fig. 2). In molecule 14a, the imidazolidine ring adopts
an envelope conformation. The hydroxy groups are loꢀ
cated on one side of the plane of the ring. The N—O
distances (1.437(3) and 1.453(3) Å) are slightly longer
than those typical of sterically hindered hydroxylamines
(1.396 Å)12 due to formation of numerous hydrogen bonds
between the hydroxy groups, the —NH— fragments, the
carbonyl O atoms of the ester groups, and the N atoms of
the pyrazole ring in the solid state.
The synthesis of nitroxide 3c requires unusual condiꢀ
tions because the reaction with the use of the calculated
14b : NaIO4 ratio of 1 : 1.5 affords a green product (preꢀ
sumably, a mixture of products). We did not perform a
special study of the nature of this product. Let us only
note that an increase in the rate of addition of NaIO4 to a
Scheme 4

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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 9, September, 2005
a
Tretyakov et al.
C(12)
D(41a) D(41b)
C(11)
O(2)
H(2A)
C(41)
C(10)
C(8)
N(4)
O(3)
C(16)
N(2)
D(41c)
O(2)
N(2)
H(7A)
C(4)
C(1)
O(4)
C(4)
O(6)
C(10)
C(9)
C(15)
C(7)
N(1)
N(3)
C(8)
C(9)
C(7)
N(1)
C(14)
C(1)
C(13)
N(3)
O(1)
O(5)
N(4)
O(1)
D(42c)
D(42a)
C(7)
D(42b)
C(42)
D(41b)
D(41a)
b
H(1A)
O(2)
Fig. 2. Molecular structure of compound 14a.
C(41)
C(10)
C(9)
regardless of the rate of addition of the oxidizer to the
CHCl3—14b—H2O system, and the organic layer turns
pale greenishꢀblue. Further mixing of the reaction mixꢀ
ture for 1 h leads to the disappearance of this precipitate,
and the organic layer turns bright blue. Darkꢀblue crystals
of 3c can be isolated from the extract in chloroform in
90—94% yield. These data suggest that nitronyl nitroxide
3c is sensitive to the presence of a large amount of NaIO4
or its reduction products in the reaction mixture. It could
be assumed that, after the addition of NaIO4, oxidation
occurs in an autocatalytic mode. However, virtually no
formation of compound 3c occurs in the presence of a
smaller amount of NaIO4 in the reaction mixture.
The solid phase of 3c consists of dimeric molecules
formed through H bonds (see Fig. 3). The N—O distances
in molecule 3c (1.277(5) and 1.280(5) Å) are typical of
nitroxides.
N(2)
C(8)
C(4)
C(1)
N(4)
N(3)
C(7)
N(1)
O(1)
Fig. 1. Molecular structures of isotopically substituted comꢀ
pounds 1c (R = CD3) (a) and 1d (R = C2D5) (b).
suspension of 14b in a CHCl3—H2O mixture led to intenꢀ
sification of the yellow tint in the color of this product.
We varied the experimental conditions of the synthesis
and found that the molar ratio 14b : NaIO4 = 1 : 0.6 is
optimum for the synthesis of the target compound 3c.
A white precipitate is rapidly formed in the aqueous phase
Scheme 5
11a, 12a
CHO
3b, 11b, 12b
COOEt
3c, 11c, 12c
13a, 14a
COOEt
COOEt
13b, 14b
COOEt
H
13c
COOH
COOH
13d
COOH
H
R1
R2
COOEt
H
H
COOEt

Pyrazolylꢀsubstituted nitronyl nitroxides
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 9, September, 2005
2173
Undoubtedly, the formation of the lead complex is
evidence that the molecular structure of 3b is favorable for
the chelate formation. Hence, we decided to oxidize 14a
with Ni2O3 with the aim of preparing the NiII complex
with 3b´ as the final product. The data from elemental
analysis, IR spectroscopy, and magnetochemistry (see
Fig. 4) for this product completely confirm our assumpꢀ
tion. These data show that the smallest formula unit corꢀ
responding to this product is Ni(3b´)2•2H2O. We believe
that the aboveꢀdescribed method for the synthesis of coꢀ
ordination compounds, which are formed by oxidation of
1,3ꢀdihydroxyimidazolidines with high oxidation state
transition metal oxides, can be used to prepare heterospin
systems.
C(13)
O(2)
C(12)
C(4)
O(4)
N(2)
C(9)
C(7)
C(11)
C(1)
N(1)
O(3)
C(10)
N(4)
C(8)
H(3a)
N(3)
O(1)
The formation of lead complexes appeared to be useꢀ
ful in the synthesis of pyrazolecarboxylic acids 3d,e. Since
aldehydes 13c,d are very poorly soluble in H2O, MeOH,
EtOH, and THF, they virtually do not react with 2.
Solutions of potassium salts of acids 13c,d rapidly reꢀ
acted with hydrosulfate 2 in a MeOH—H2O mixture to
form the corresponding 1,3ꢀdihydroxyimidazolidine deꢀ
rivatives, which were oxidized with PbO2 without isolaꢀ
tion. The reaction with 13c afforded a paramagnetic salt.
The elemental analysis data for this compound are most
consistent with the composition K33d´. In the case of
acid 13d, the lead complex Pb(K3e´)2 was isolated, where
3d´ and 3e´ are deprotonated pyrazole derivatives of the
corresponding diꢀ and monocarboxylates. Crystallization
from a MeOH—toluene mixture gave Pb(K3e´)2 as the
solvate with MeOH (Scheme 6).
Treatment of an ethanolic solution of K33d´ with two
equivalents of H2SO4 in EtOH resulted in a change in the
color of the reaction mixture from violet to red. An atꢀ
tempt to crystallize the reaction products led to the forꢀ
mation of a finely dispersed yellow powder and pale brown
crystals. The crystals were suitable for Xꢀray diffraction,
which allowed us to study the structure of this product.
The crystals are composed of the ions of compounds 15
(Fig. 5) generated as a result of acidꢀpromoted disproporꢀ
tionation typical of nitronyl nitroxides.14 The deprotoꢀ
nated carboxy group at position 5 of the pyrazole ring
(dC—O = 1.249(2) and 1.252(2) Å) in the solid phase of 15
Fig. 3. Mode of dimerization of molecules 3c (the hydrogen
atoms of the alkyl groups are omitted).
In the course of oxidation of 14a giving rise to nitronyl
nitroxide, we attempted to replace NaIO4 with PbO2,
which is widely used for this purpose.13 As a result,
we prepared a product, whose crystallization from an
H2O—MeOH mixture afforded an Xꢀray amorphous
blackꢀblue film that cracked during drying. Recrystalliꢀ
zation of this product from CH2Cl2—heptane,
CH2Cl2—ethyl acetate, or acetone—toluene mixtures afꢀ
forded a finely dispersed blue powder, which did not alꢀ
low us to study its structure by Xꢀray diffraction. Elemenꢀ
tal analysis of this product showed that its composition
corresponds to the formula Pb3O2(3b´)2, where 3b´
is deprotonated compound 3b. The highꢀtemperature
asymptotics of the magnetic moment µeff, which was
calculated with the use of the molecular weight of
Pb3O2(3b´)2 (Fig. 4), also agrees well with the theoretical
magnetic moment for biradicals (2.45 µB).
µ
eff/µ
B
3.6
3.3
3.0
2.7
2.4
2.1
2
H(3)
H(2)
N(2)
C(7)
N(4)
C(8)
O(5)
N(3)
C(4)
C(11)
1
C(12)
O(4)
C(1)
N(1)
C(10)
H(1)
H(3a)
O(3)
50
100
150
200
250
T/K
O(1)
O(2)
Fig. 4. Temperature dependences of the effective magnetic moꢀ
ments for Pb3O2(3b´)2 (1) and Ni(3b´)2•2H2O (2).
Fig. 5. Molecular structure of compound 15.

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Russ.Chem.Bull., Int.Ed., Vol. 54, No. 9, September, 2005
Tretyakov et al.
Scheme 6
3d´: R1 = R2 = CO2
;
–
3d″, 15: R1 = CO2–, R2 = CO2H;
3e´: R1 = CO2–, R2 = H;
3e: R´ = COOH, R2 = H
forms an intramolecular H bond with the carboxy group
at position 4 (dC=O = 1.215(2), dC—OH = 1.311(2) Å).
In addition, the O atoms of the carboxy groups are
involved in hydrogen bonding with the protonated
HO—N—C=N+—H fragments (dN—O, 1.375(2) Å;
dN—C, 1.312(2) and 1.322(2) Å) of the imidazolidine rings
of the adjacent molecules, resulting in the formation of a
framework structure.
Finely dispersed redꢀviolet monopotassium salt K3d″
was isolated from the mother liquor obtained after isolaꢀ
tion of crystals of 15. The magnetic moment µeff for K3d″
(1.72 µB at 300 K) agrees well with the theoretical value
for monoradicals (1.73 µB). Treatment of an ethanolic
solution of K3d″ with an equivalent amount of H2SO4 led
to the gradual disappearance of the redꢀviolet color of the
reaction mixture. The reaction mixture was concentrated,
after which a yellowꢀbrown residue was obtained. Washꢀ
ing of the latter with water followed by recrystallization
from EtOH afforded a colorless product. Therefore, a
spinꢀlabeled dicarboxylic acid cannot be isolated accordꢀ
ing to this procedure.
Treatment of a methanolic solution of Pb(K3e´)2 with
an equivalent amount of sulfuric acid gave rise to acid 3e
in 40% yield (after purification) (see Scheme 6). Single
crystals of acid 3e were grown as the crystal hydrate
3e•H2O. Study of its structure demonstrated that the solid
phase consists of ribbons stabilized by an extensive hydroꢀ
gen bond network (Fig. 6). Since the O atom of only one
NO group is involved in hydrogen bonding, dN—O in this
group is slightly larger than that in another group (1.287(2)
and 1.270(2) Å, respectively). High purity of the resulting
acid is supported also by magnetic property measurements.
C(1)
O(1)
C(4)
N(1)
N(2)
C(8)
O(2)
N(3)
C(9)
O(4)
H(4)
H(3)
N(4)
C(10)
O(3)
O(1w)
H(1wa)
H(1wb)
Fig. 6. Hydrogen bond network giving rise to polymeric ribbons in 3e•H2O (the hydrogen atoms of the methyl groups are omitted).

Pyrazolylꢀsubstituted nitronyl nitroxides
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 9, September, 2005
2175
O(2a)
O(2)
The magnetic moment µeff of (3e•H2O) (1.734(2) µB in
the temperature range of 77—300 K) is equal to the theoꢀ
retical value (calculations based on the number of elecꢀ
trons) for free monoradicals (g = 2.00) to within three
decimal points.
Unlike acetals 12b,c, compound 12a has no ester
groups, due to which it was directly used in the reaction
with 2•H2SO4•H2O. After neutralization of the reaction
mixture, CHCl3 was added, and bis(dihydroxyimidꢀ
azolidino)pyrazole that was present in the mixture was
oxidized in the twoꢀphase system with NaIO4 to give
bis(nitronyl nitroxide) 4 (Scheme 7).
C(4a)
N(2a)
C(7a)
N(2)
C(9)
C(1a)
N(1a)
O(1a)
C(4)
C(1)
C(7)
C(8a)
C(8)
N(3)
N(1)
O(1)
N(3a)
H(3d)
Scheme 7
Fig. 7. Mode of dimerization of molecules 4 (the hydrogen atoms
of the methyl groups are omitted).
based on the initial preparation of the required pyrazole
derivatives by 1,3ꢀdipolar addition is rather efficient and
allows the synthesis of a wide range of polyfunctional
nitroxides. The use of 1,3ꢀdipolar addition as the initial
step of the synthesis made it possible to prepare the previꢀ
ously inaccessible mononitronyl nitroxides 3b—e and
bis(nitronyl nitroxide) 4, whose structures were confirmed
by Xꢀray diffraction study.
In this case, as in the aboveꢀdescribed process with 3c,
the use of a 12a : NaIO4 molar ratio of 1 : 3 (i.e., 1 : 1.5
with respect to one 1,3ꢀdihydroxyimidazolidine (DHI)
fragment) resulted in the rapid formation of a yelꢀ
lowꢀbrown polymerꢀlike mixture. A decrease in the
12a : NaIO4 ratio to 1 : 2 (i.e., 1 : 1 with respect to one
DHI fragment) led to the formation of a blueꢀgreen prodꢀ
uct, which can be separated into two individual comꢀ
pounds: biradical 4 (~17%) and a green product of unꢀ
known structure. The elemental analysis data are indicaꢀ
tive of the presence of iodine in the latter product. Reꢀ
crystallization of this product afforded a solid phase as
Xꢀray amorphous green intergrown spherical particles.
Only once, crystallization of this product from a mixture
of CH2Cl2 and benzene during three weeks gave several
small green crystals, which are (Xꢀray diffraction data)
nitroxide 16.
Experimental
The course of the reactions was monitored by TLC on Aluꢀ
minum oxide on aluminum sheets, 60 F254 neutral, and Silica
gel 60 F254 aluminum sheets (Merck). Column chromatography
was carried out on silica gel (0.063—0.200 mm; Merck) and
Al2O3 (chromatographic grade) purchased from the Donetsk
Plant of Chemical Reagents. The IR spectra were recorded in
the 400—4000 cm–1 region on a VECTORꢀ22 Bruker spectroꢀ
photometer (KBr pellets). The melting points were determined
on a Boetius microheating table. Microanalyses were performed
on a Carlo Erba 1106 analyzer at the Vorozhtsov Novosibirsk
Institute of Organic Chemistry of the Siberian Branch of the
Russian Academy of Sciences. The mass spectra were obtained
on a Finnigan MATꢀ8200 mass spectrometer (electron impact
ionization, 70 eV). The molecular weights of the anions in the
salts Pb3O2(3b´)2, K33d´•2H2O, Pb(K3e´)2•3MeOH, and K3d″
were determined using a massꢀselective detector (G1946C,
Agilent 1100 Serie LC/MSD), which was used in electrostatic
spray mode (APIꢀAS); the negative ions were scanned in the
m/z range from 100 to 1000. The NMR spectra were recorded
on a Bruker Avance 300 spectrometer at room temperature
(23—26 °C) using the signal of the solvent as the internal stanꢀ
dard (δ = 7.24 for CDCl3 and δ = 2.05 for acetoneꢀd6). The
We found that the highest yield of 4 (47%) was achieved
with the use of the 12a : NaIO4 molar ratio of 1 : 1.6
(or 1 : 0.8 with respect to one DHI fragment). Slow evapoꢀ
ration of a solution of bis(nitronyl nitroxide) 4 from a
CH2Cl2—heptane mixture afforded wellꢀfaceted darkꢀblue
crystals. The structure of the dimeric molecules is shown
in Fig. 7. The magnetic moment µeff for 4 (2.41 µB at
77—300 K) agrees well with the theoretical value for
biradicals (2.45 µB).
H
H
magnetic measurements were performed on a SQUID MPMSꢀ5S
(Quantum Desing) magnetometer in the temperature range
of 2—300 K at 5 kOe.
Dimethyl sulfateꢀd6 (>99%, Aldrich), NaH (60% in mineral
oil), DMF (99.8%, Aldrich), and NaIO4 (>99.5%, Fluka) were
used without additional purification. 2,3ꢀBis(hydroxyamino)ꢀ
To summarize, we demonstrated that the approach to
the synthesis of pyrazoleꢀsubstituted nitronyl nitroxides

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Tretyakov et al.
2,3ꢀdimethylbutane (2), its sulfate hydrate 2•H2SO4•H2O,15,16
3,3ꢀdiethoxypropꢀ1ꢀyne,17 and 1ꢀmethylꢀ1ꢀnitrosourea18 were
synthesized according to known procedures. The reagent C2D5I
was prepared from anhydrous C2D5OD according to a proceꢀ
dure developed for the synthesis of C2H5I.19 The Pb content
in the complexes was determined by chelate titration with
Eriochrome Black T as the indicator.20
1ꢀ(2,2ꢀDimethoxyethyl)urea was synthesized according to
two methods (A and B). A. 1ꢀ(2,2ꢀDimethoxyethyl)urea21 was
prepared from 2,2ꢀdimethoxyethylamine (12 g, 0.11 mol) and
KOCN (10 g, 0.12 mol) in a yield of 16 g (98%). B. A mixture of
urea (12.2 g, 0.2 mol) and 2,2ꢀdimethoxyethylamine (21.4 g,
0.2 mol) was heated to 140—150 °C and stirred at this temperaꢀ
ture for 6 h. Elimination of ammonia started at 100 °C and
occurred extensively during the first hour. The reaction mixture
was cooled, and Et2O (~100 mL) was added to the resulting
viscous paleꢀyellow oil. Trituration of the product caused its
crystallization. The finely dispersed white precipitate was filꢀ
tered off. The mother liquor was concentrated and stored in a
refrigerator, after which an additional amount of crystals was
obtained. The total yield was 23.4 g (78%), m.p. 55—56 °C
(hexane—AcOEt). IR, ν/cm–1: 726, 832, 885, 1067, 1311, 1364,
1435, 1656, 2936, 3442. 1H NMR (CDCl3), δ: 3.34 (d, 2 H,
CH2, J = 7.0 Hz); 3.43 (s, 6 H, (OCH3)2); 4.2 (br.s, NH); 4.41
(t, 1 H, CH, J = 7.0 Hz); 5.1 (br.s, NH2).
1ꢀ(2,2ꢀDimethoxyethyl)ꢀ1ꢀnitrosourea was synthesized
analogously to 1ꢀ(2,2ꢀdiethoxyethyl)ꢀ1ꢀnitrosourea22, m.p.
63—64 °C (hexane). IR, ν/cm–1: 697, 775, 814, 867, 943, 1009,
1062, 1129, 1206, 1295, 1421, 1484, 1607, 1738, 2841, 2946,
3401. 1H NMR (CDCl3), δ: 3.30 (s, 6 H, (OCH3)2); 3.98 (d,
2 H, CH2, J = 7.0 Hz); 4.51 (t, 1 H, CH, J = 7.0 Hz); 5.60 and
6.80 (both br.s, 1 H each, NH). Found (%): C, 34.1; H, 6.2;
N, 23.7. C5H11N3O4. Calculated (%): C, 33.9; H, 6.3; N, 23.7.
2,2ꢀDimethoxydiazoethane was synthesized analogously to
2,2ꢀdiethoxyꢀ1ꢀdiazoethane.22,23
4,4,5,5ꢀTetramethylꢀ2ꢀ(1Hꢀpyrazolꢀ4ꢀyl)ꢀ4,5ꢀdihydroꢀ1Hꢀ
imidazoleꢀ1ꢀoxyl 3ꢀoxide (1a, R = H) and 4,4,5,5ꢀtetramethylꢀ
2ꢀ(1Hꢀpyrazolꢀ3ꢀyl)ꢀ4,5ꢀdihydroꢀ1Hꢀimidazoleꢀ1ꢀoxyl 3ꢀoxide
(3a, R1 = R2 = H). 1ꢀMethylꢀ1ꢀnitrosourea (14.4 g, 0.14 mol)
was added portionwise to an iceꢀcooled mixture of a 40% aqueꢀ
ous KOH solution (60 g) and Et2O (100 mL) for 1 h. After the
addition of each portion of 1ꢀmethylꢀ1ꢀnitrosourea, the reacꢀ
tion mixture was shaken manually for about 1 min. The resulting
solution of diazomethane in Et2O (CAUTION! Diazomethane is
a highly toxic compound irritating mucous membranes. In addiꢀ
tion, it readily detonates. Hence, special precautions should be
taken, such as specially chosen glassware, a protecting screen, etc.)
was decanted into an iceꢀcooled flatꢀbottomed vessel containing
3,3ꢀdiethoxypropꢀ1ꢀyne (5) (5.0 g, 6.1 mL, 0.039 mol). The
reaction mixture was kept at ~20 °C for 4 days, after which it
became completely colorless. Diethyl ether was distilled off unꢀ
der standard pressure, and alkyne 5 was distilled off in vacuo at
15 Torr and a bath temperature of 50 °C. An yellow oil containꢀ
ing acetal 6 was obtained in a yield of 6.06 g. The independent
synthesis afforded the oil in a yield of 6.72 g.
was transferred to a filter, pressed, and suspended in acetone
(200 mL). The insoluble precipitate was filtered off and dried in
air, and to prepare a paleꢀyellow powder containing imidꢀ
azolidines 8 and 9 (28 g), which were oxidized without addiꢀ
tional purification.
Sodium periodate (13 g, 0.06 mol) was added portionwise to
a stirred solution of the powder (28 g) prepared in the previous
step in a mixture of CHCl3 (100 mL) and H2O (50 mL) at
3—5 °C for 30 min. The reaction mixture was filtered off, the
organic phase was separated, and the aqueous phase was addiꢀ
tionally treated with CHCl3 (4×20 mL). The combined organic
extracts were dried with Na2SO4, the solvent was distilled off,
and the residue was chromatographed on an Al2O3 column
(25×2 cm). Chloroform was used as the first eluent until nitroxide
1a appeared in the eluate. Then the column was eluted with
EtOH, and the fraction containing 1a was collected. The ethaꢀ
nol fraction was concentrated, and the residue was recrystallized
from a CH2Cl2—benzene mixture. The chloroform fraction was
concentrated, and the residue was dissolved in hot benzene
(~30 mL) and applied onto a silica gel column (25×2 cm) eluted
with CHCl3, an orange fraction containing nitroxide 10 being
eluted first, after which a blue fraction containing nitroxide 3a
was eluted.
Compound 1a. The yield was 4.4 g (25% with respect to 10 g
of 3,3ꢀdiethoxypropyne 5), blue crystals, Rf (Al2O3, AcOEt)
0.19, Rf 0.25 (silica gel, AcOEt) 0.25, m.p. 192—192.5 °C (from
a benzene—hexane mixture); µeff = 1.72 µB (300 K). IR, ν/cm–1
:
662, 670, 749, 809, 868, 899, 938, 961, 995, 1041, 1127, 1154,
1172, 1216, 1283, 1313, 1342, 1369, 1396, 1409, 1434, 1458,
1520, 1608, 2989, 3119, 3200. Found (%): C, 53.9; H, 6.7;
N, 25.2. C10H15N4O2. Calculated (%): C, 53.8; H, 6.8; N, 25.1.
Compound 3a. The yield was 0.56 g (6.4% with respect to
10 g of 5), blueꢀviolet crystals, Rf 0.30 (Al2O3, AcOEt), Rf (silica
gel, AcOEt) 0.44, m.p. 148—149 °C (from a benzene—hexane
mixture); µeff = 1.73 µB (300 K). IR, ν/cm–1: 765, 817, 870, 901,
921, 1016, 1037, 1098, 1137, 1190, 1210, 1242, 1270, 1299,
1374, 1406, 1428, 1453, 1494, 2992, 3283 br. Found (%):
C, 53.9; H, 6.5; N, 24.8. C10H15N4O2. Calculated (%): C, 53.8;
H, 6.8; N, 25.1.
4,4,5,5ꢀTetramethylꢀ2ꢀ(1Hꢀpyrazolꢀ3ꢀyl)ꢀ4,5ꢀdihydroꢀ1Hꢀ
imidazoleꢀ1ꢀoxyl (10). A mixture of 3a (250 mg, 1.12 mmol),
NaNO2 (150 mg, 2.17 mmol), CHCl3 (15 mL), HOAc (0.2 mL),
and H2O (0.2 mL) was stirred at 40—45 °C until the starting
nitronyl nitroxide was consumed (2 h). The cooled reaction
mixture was neutralized with NaHCO3, dried with Na2SO4, and
filtered through a layer of Al2O3. The solvent was distilled off,
the residue was chromatographed on an Al2O3 column (25×2 cm)
eluted with benzene, and an orange fraction was collected.
The yield was 120 mg (52%), red needleꢀlike crystals, m.p.
151—152 °C (from a benzene—hexane mixture); µ = 1.73 µ
eff
B
(300 K). IR, ν/cm–1: 561, 602, 624, 721, 781, 829, 857, 881,
920, 1053, 1097, 1147, 1169, 1221, 1249, 1269, 1289, 1353,
1369, 1422, 1463, 1481, 1546, 1591, 2941, 3047, 3149 br.
Found (%): C, 58.2; H, 7.4; N, 26.9. C10H15N4O. Calcuꢀ
lated (%): C, 58.0; H, 7.3; N, 27.0.
The compound 2•H2SO4•H2O (21.0 g, 0.080 mol) was
added with stirring into a 300 mL beaker containing a mixture of
the oil prepared in the previous step (12.8 g) and water (40 mL).
The solution was stirred for 5 h during which it gradually beꢀ
came viscous. The yellow creamꢀlike substance was carefully
neutralized with NaHCO3 (18 g). The resulting sticky substance
4,4,5,5ꢀTetramethylꢀ2ꢀ(1ꢀtrideuteriomethylꢀ1Hꢀpyrazolꢀ4ꢀ
yl)ꢀ4,5ꢀdihydroꢀ1Hꢀimidazoleꢀ1ꢀoxyl 3ꢀoxide (1c). Sodium hyꢀ
dride (60% in mineral oil, 60 mg, 1.5 mmol) was added to a
stirred solution of nitroxide 2a (330 mg, 1.5 mmol) in DMF
(6 mL) at room temperature under argon. The reaction mixture
was stirred for 20 min, dimethyl sulfateꢀd6 (150 µL, 200 mg,

Pyrazolylꢀsubstituted nitronyl nitroxides
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 9, September, 2005
2177
1.5 mmol) was added, and the reaction mixture was stirred for
30 min. The solvent was distilled off at a bath temperature of
~60 °C, CHCl3 (20 mL) was added to the residue, the solution
was filtered through a layer of silica gel (1.5×6 cm), and the
product was eluted with ethyl acetate. The blue fraction was
concentrated, and the residue was chromatographed on an Al2O3
column (1.5×20 cm) eluted with CHCl3. The product was reꢀ
crystallized from a 1 : 1 benzene—hexane mixture. The yield
was 310 mg (86%), m.p. 174—175 °C (from a 1 : 1 benzene—hepꢀ
tane mixture); µeff = 1.72 µB (300 K). IR, ν/cm–1: 543, 664, 754,
814, 832, 865, 984, 1017, 1078, 1136, 1180, 1224, 1317, 1347,
1371, 1397, 1428, 1456, 1481, 1600, 2076, 2122, 2162, 2980,
3147. Highꢀresolution MS. Found: m/z = 240.1576 [M]+.
C11H14D3N4O2. Calculated: M = 240.1540. MS, m/z (Irel (%)):
241 [M+1]+ (12), 240 [M]+ (100), 178 (10), 112 (52), 111 (22),
84 (40), 83 (16), 69 (59), 56 (71), 55 (30). Found (%): C, 55.1;
H+D, 7.1; N, 23.3. C11H14D3N4O2. Calculated (%): C, 55.0;
H+D, 7.1; N, 23.3.
4,4,5,5ꢀTetramethylꢀ2ꢀ(1ꢀpentadeuterioethylꢀ1Hꢀpyrazolꢀ4ꢀ
yl)ꢀ4,5ꢀdihydroꢀ1Hꢀimidazoleꢀ1ꢀoxyl 3ꢀoxide (1d) was syntheꢀ
sized analogously with the use of iodoethaneꢀd5 (130 µL, 240 mg,
1.5 mmol). After completion of the synthesis and removal of the
solvent, C6H6 (20 mL) was added to the residue. The solution
was filtered and concentrated. The yield was 320 mg (83%),
m.p. 100—103 °C, µeff = 1.73 µB (300 K). IR, ν/cm–1: 542, 665,
866, 985, 1018, 1140, 1181, 1223, 1315, 1347, 1399, 1428, 1451,
1601, 2075, 2124, 2141, 2169, 2233, 2872, 2931, 2979, 3002,
3145. MS, m/z (Irel (%)): 257 [M + 1]+ (9), 256 [M]+ (69), 168
(14), 128 (38), 127 (33), 114 (13), 96 (12), 95 (13), 94 (11),
84 (92), 83 (14), 69 (83), 56 (100). Found (%): C, 56.4;
H+D, 7.8; N, 22.0. C12H14D5N4O2. Calculated (%): C, 56.2;
H+D, 7.6; N, 21.9.
Diethyl 3ꢀformylꢀ1Hꢀpyrazoleꢀ4,5ꢀdicarboxylate (13a). A soꢀ
lution of 2,2ꢀdimethoxydiazoethane in diethyl ether, which was
prepared from 1ꢀ(2,2ꢀdimethoxyethyl)ꢀ1ꢀnitrosourea (7.0 g,
40 mmol), was added dropwise to a stirred solution of diethyl
acetylenedicarboxylate (4.8 g, 28 mmol) in diethyl ether (20 mL)
at 0 °C. The solvent was distilled off in vacuo, HCO2H (11 mL)
was added to the oily residue (10.4 g), and the mixture was
stirred for 6 h. The white precipitate that formed was filtered off
and washed with diethyl ether. The yield was 4.16 g (50%), m.p.
139—144 °C. IR, ν/cm–1: 615, 756, 873, 950, 1022, 1087, 1157,
1200, 1227, 1320, 1369, 1410, 1452, 1492, 1547, 1703, 1739,
2980, 3311. Found (%): C, 49.9; H, 5.1; N, 11.5. C10H12N2O5.
Calculated (%): C, 50.0; H, 5.0; N, 11.7.
Ethyl 3ꢀformylꢀ1Hꢀpyrazoleꢀ5ꢀcarboxylate (13b). Ethyl
propiolate (1.9 mL, 19 mmol) was added to an yellow solution
of 2,2ꢀdimethoxydiazoethane in diethyl ether, which was preꢀ
pared from 1ꢀ(2,2ꢀdimethoxyethyl)ꢀ1ꢀnitrosourea (2.66 g,
15 mmol). The reaction mixture was refluxed with stirring for
30 min, during which it gradually turned colorless. The solvent
was distilled off in vacuo, HCO2H (3.3 mL) was added to the
oily residue (3.23 g), and the solution was stirred for 1 h. The
finely dispersed paleꢀyellow precipitate that formed was filtered
off and washed with diethyl ether. The yield was 1.50 g (60%),
m.p. 136—138 °C. IR, ν/cm–1: 780, 819, 841, 897, 995, 1034,
1065, 1104, 1173, 1205, 1242, 1295, 1365, 1385, 1457, 1724,
1743, 2984, 3184. 1H NMR (acetoneꢀd6), δ: 1.36 (t, 3 H, Me,
J = 7.0 Hz); 4.38 (к, 2 H, CH2, J = 7.0 Hz); 7.27 (br.s, 1 H,
C—HPyr); 9.98 (s, 1 H, CHO). Found (%): C, 50.1; H, 4.8;
N, 16.6. C7H8N2O3. Calculated (%): C, 50.0; H, 4.8; N, 16.7.
3ꢀFormylꢀ1Hꢀpyrazoleꢀ4,5ꢀdicarboxylic acid (13с). A 10%
aqueous NaOH solution (20 mL) was added with stirring to a
suspension of 13a (2.0 g, 8.3 mmol) in MeOH (2 mL). The
resulting paleꢀyellow solution was stirred for 6 h, and a concenꢀ
trated aqueous HCl solution was added dropwise to pH ~3. After
15 min, the finely dispersed white precipitate that formed was
filtered off, washed with a weak aqueous HCl solution, pH 3,
and dried in air. The yield was 1.38 g (90%). IR, ν/cm–1: 784,
864, 947, 1066, 1124, 1171, 1229, 1301, 1328, 1476, 1559, 1591,
2758, 2872, 3355, 3606. Satisfactory results of elemental analyꢀ
sis were not obtained because 13с is very poorly soluble and is
prone to decarboxylation on heating. Found (%): C, 27.0; H, 2.0;
N, 10.0. The C : N ratio was 2.7. C6H4N2O5. Calculated (%):
C, 39.1; H, 2.2; N, 15.2. The C : N ratio was 2.6. Compound
13с was used without additional purification.
2ꢀ(1ꢀCarbamoylmethylꢀ1Hꢀpyrazolꢀ4ꢀyl)ꢀ4,4,5,5ꢀtetraꢀ
methylꢀ4,5ꢀdihydroꢀ1Hꢀimidazoleꢀ1ꢀoxyl 3ꢀoxide (1e) was
synthesized analogously. The yield was 54 mg (71%), m.p.
206—208 °C (from toluene), µeff = 1.72 µB (300 K). IR, ν/cm–1
:
540, 618, 792, 820, 839, 868, 896, 964, 1005, 1127, 1172, 1202,
1320, 1353, 1408, 1435, 1461, 1484, 1606, 1682, 2937, 2988,
3193, 3382. Highꢀresolution MS. Found: m/z 280.1409 [M]+.
C
12H18N5O3. Calculated: M = 280.1410. MS, m/z (Irel (%)):
281 [M + 1]+ (13), 280 [M]+ (89), 152 (35), 151 (16), 106 (11),
84 (95), 83 (20), 69 (96), 56 (100). Found (%): C, 50.2;
H, 6.4; N, 24.2. C12H18N5O3•0.5H2O. Calculated (%): C, 49.8;
H, 6.6; N, 24.2.
3ꢀ(Dimethoxymethyl)ꢀ1Hꢀpyrazoleꢀ5ꢀcarbaldehyde (12a).
Acetal 5 (2.15 g, 2.4 mL, 16.8 mmol) was added with stirring to a
mixture of 0.2 N H2SO4 (4 mL) and hydroquinone (8 mg) at
80 °C. Propiolaldehyde that formed was distilled off through a
descending condenser into a stirred solution of 2,2ꢀdimethoxyꢀ
diazoethane in diethyl ether (~50 mL), which was prepared
from 1ꢀ(2,2ꢀdimethoxyethyl)ꢀ1ꢀnitrosourea (1.5 g, 8.5 mmol).
The starting brightꢀyellow reaction mixture gradually turned
paleꢀpink. After completion of the addition of propiolaldehyde,
the reaction mixture was stirred for 20 min and concentrated.
The residue was triturated with hexane on cooling, and the
creamyꢀcolored precipitate was filtered off. The yield was
1.18 g (82%), m.p. 128—131 °C. IR, ν/cm–1: 858, 915, 982,
1022, 1060, 1102, 1141, 1178, 1194, 1222, 1290, 1334, 1362,
1401, 1447, 1474, 2835, 2905, 2968, 3146 br. Found (%):
C, 49.5; H, 6.0; N, 16.2. C7H10N2O3. Calculated (%): C, 49.4;
H, 5.9; N, 16.5.
3ꢀFormylꢀ1Hꢀpyrazoleꢀ5ꢀcarboxylic acid (13d). A 5% aqueꢀ
ous NaOH solution (18 mL) was added to a stirred suspension of
13b (0.8 g, 4.8 mmol) in MeOH (5 mL). After 4 h, concentrated
HCl was added dropwise to the solution to pH ~0. The white
precipitate that formed was filtered off, washed with a weak
aqueous HCl solution, pH 3, and dried in air. The yield was
0.60 g (90%). IR, ν/cm–1: 768, 782, 821, 843, 900, 1009, 1076,
1110, 1172, 1218, 1272, 1399, 1453, 1495, 1548, 1706, 2608,
2758, 3158. Highꢀresolution MS. Found: m/z 140.0210 [M]+.
C5H4N2O3. Calculated: M = 140.0222. MS, m/z (Irel (%)): 141
[M + 1]+ (6.7), 140 [M]+ (100), 139 [M – H] (33), 121
[M – H2O] (59), 112 [M – CO] (41), 96 (14). Found (%):
C, 42.0; H, 2.8; N, 19.0. C5H4N2O3. Calculated (%): C, 42.9;
H, 2.9; N, 20.0.
Diethyl 3ꢀ(1,3ꢀdihydroxyꢀ4,4,5,5ꢀtetramethylimidazolidinꢀ2ꢀ
yl)ꢀ1Hꢀpyrazoleꢀ4,5ꢀdicarboxylate (14a). A solution of aldehyde
13a (2.0 g, 8.3 mmol) and 2 (1.23 g, 8.3 mmol) in methanol

2178
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 9, September, 2005
Tretyakov et al.
(40 mL) was stirred for 5 h. Then the solvent was distilled off.
The paleꢀyellow oily product was dissolved in a minimum
amount of diethyl ether, hexane was added, and the reaction
mixture was kept at ~0 °C for several days. The product was
initially obtained as an oil, which gradually crystallized. The
colorless crystals were filtered off, the yield was 3.0 g (98%),
m.p. 114—118 °C. IR, ν/cm–1: 579, 770, 812, 862, 1019, 1091,
1161, 1223, 1296, 1368, 1469, 1703, 1724, 2983, 3287, 3448.
1H NMR (acetoneꢀd6), δ: 1.13 (s, 6 H, C(CH3)2); 1.17 (s, 6 H,
C(CH3)2); 1.31 and 1.33 (both t, 3 H each, C(4)CO2CH2CH3,
C(5)CO2CH2CH3, J = 7.1 Hz); 4.23 and 4.31 (both q, 2 H each,
C(4)CO2CH2, C(5)CO2CH2, J = 7.1 Hz); 5.41 (s, 1 H, H(2´));
7.2 (br.s, 1.6 H). Found (%): C, 52.2; H, 7.2; N, 15.3.
C16H26N4O6. Calculated (%): C, 51.9; H, 7.1; N, 15.1.
Ethyl 3ꢀ(1,3ꢀdihydroxyꢀ4,4,5,5ꢀtetramethylimidazolidinꢀ2ꢀ
yl)ꢀ1Hꢀpyrazoleꢀ5ꢀcarboxylate (14b). Compound 2 (0.45 g,
3 mmol) was added to a solution of aldehyde 13b (0.5 g, 3 mmol)
in methanol (10 mL), and the reaction mixture was stirred for 3 h.
The solvent was distilled off, the resulting oil was dissolved in a
minimum amount of ethyl acetate, and benzene was added.
Then the solution was cooled and ground with a rod, which gave
rise to a finely dispersed white precipitate. The latter was filtered
off and washed on a filter with hexane. The yield was 0.58 g
(65%), m.p. 140—143 °C. IR, ν/cm–1: 779, 849, 996, 1025,
1180, 1240, 1265, 1299, 1337, 1373, 1387, 1411, 1444, 1465,
1710, 2932, 2985, 3137, 3294, 3388. Found (%): C, 49.6;
H, 8.0; N, 17.6. C13H22N4O4•H2O. Calculated (%): C, 49.4;
H, 7.7; N, 17.7.
(10 mL) for 5 min. The formation of a white substance in the
aqueous phase was observed, and the organic phase turned paleꢀ
blue. The poorly soluble compound gradually disappeared in the
course of stirring of the reaction mixture for 1.5 h, and the
chloroform layer turned brightꢀblue. The organic layer was sepaꢀ
rated, and the aqueous phase was extracted with chloroform
(2×5 mL). The combined organic solutions were dried with
Na2SO4 and filtered through a layer of silica gel (1.5×3 cm). The
solvent was removed, and the oily darkꢀblue residue was disꢀ
solved in a mixture of hexane and benzene. The solution
was decanted, the grayꢀgreen byꢀproduct remaining on the walls
of the flask. Then the solution was applied onto a silica gel
column (1.5×15 cm) eluted with CHCl3, and a blueꢀviolet fracꢀ
tion was collected. The latter was concentrated, and an oil was
obained in a yield of 1.90 g. The oil was kept in vacuo at 40 °C
for 16 h. Compound 3b was obtained as a darkꢀblue oil in a
yield of 1.50 g (82%). IR, ν/cm–1: 540, 773, 847, 1036,
1096, 1171, 1219, 1292, 1372, 1415, 1449, 1633, 1727, 2934,
2986, 3453. Highꢀresolution MS. Found: m/z 367.1623 [M]+.
C16H23N4O6. Calculated: M = 367.1618. MS, m/z (Irel (%)):
367 (2) 250 (16), 164 (12), 84 (100), 69 (30), 56 (17). Found (%):
C, 51.7; H, 6.4; N, 14.7. C16H23N4O6. Calculated (%): C, 52.3;
H, 6.3; N, 15.3.
Complex Pb3O2(3b´)2 (3b´ is deprotonated 3b). Lead oxide
(1 g, 4.2 mmol) was added to a solution of 14a (0.5 g, 1.4 mmol)
in methanol (5 mL). The reaction mixture was stirred for 2 h
and filtered. The solution was concentrated, and the oily darkꢀ
blue residue was triturated with a mixture of hexane and ethyl
acetate, resulting in crystallization. The precipitate was filtered
off, washed with hexane, and dried in air. The yield was 0.2 g.
The compound decomposes at ~220—230 °C, is poorly soluble
in H2O, AcOEt, toluene, and diethyl ether, and is readily soluble
Diethyl 3ꢀ(4,4,5,5ꢀtetramethylꢀ3ꢀoxidoꢀ1ꢀoxylꢀ4,5ꢀdihydroꢀ
1Hꢀimidazolꢀ2ꢀyl)ꢀ1Hꢀpyrazoleꢀ4,5ꢀdicarboxylate (3b). Sodium
periodate (1.6 g, 7.5 mmol) was added portionwise to a stirred
mixture of 14a (1.8 g, 5 mmol), chloroform (40 mL), and water
Table 1. Principal crystallographic data and details of Xꢀray diffraction studies
Parameter
1a
1c
1d
3a
Space group
a/Å
b/Å
c/Å
α/deg
β/deg
γ/deg
V/Å
P–1
7.1757(15)
13.026(3)
14.057(3)
63.902(4)
80.129(4)
86.402(4)
1162.4(4)
4
1.276
0.094
1.74—23.25
5593
P21/n
P21/n
C2/c
9.6638(11)
11.4304(12)
11.7101(13)
9.8305(16)
11.6094(19)
11.979(2)
23.522(4)
7.8792(13)
12.417(2)
108.214(2)
105.223(3)
101.013(4)
1228.7(2)
4
1.299
0.091
2.39—23.28
8698
1319.1(4)
4
1.291
0.089
2.39—23.27
5196
2259.0(7)
8
1.313
0.095
2.73—23.30
4741
Z
dcalc/g cm–3
µ/mm–1
θ Scan range/deg
Number of measured reflections
Number of independent reflections
1895
3315
1756
1637
Rint
0.0682
2158
0.0316
1307
0.0555
1682
0.0559
1064
Reflections with I > 2σ(I )
Number of parameters in refinement
392
223
240
206
R factors (I > 2σ)
R1
wR2
0.0496
0.1072
0.0373
0.1021
0.0403
0.1149
0.0493
0.1226
R factors (all reflections)
R1
wR2
GOOF
0.0780
0.1196
0.857
0.0537
0.1138
0.740
0.0506
0.1246
0.878
0.0799
0.1426
0.785

Pyrazolylꢀsubstituted nitronyl nitroxides
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 9, September, 2005
2179
in CH2Cl2, acetone, MeOH, and EtOH. Crystallization of
Pb3O2(3b´)2 from CH2Cl2—heptane, CH2Cl2—AcOEt, and acꢀ
etone—toluene solvent mixtures afforded a finely dispersed blue
powder. Recrystallization of Pb3O2(3b´)2 from a MeOH—H2O
mixture gave a blackꢀblue film on the bottom of the flask, and
the film cracked during drying in air. The fingerprint regions of
the IR spectra of the samples obtained by crystallization from
different solvents are identical. IR, ν/cm–1: 775, 850, 874, 1050,
1098, 1138, 1169, 1215, 1249, 1298, 1337, 1370, 1396, 1461,
1515, 1571, 1721, 2936, 3283, 3436. MS, m/z (Irel (%)): 367
[3b´ + 1]– (7), 366 [3b´]– (47), 352 (100), 336 (77). Found (%):
C, 27.5; H, 2.9; N, 8.4; Pb, 42.2. C32H44N8O14Pb3. Calcuꢀ
lated (%): C, 27.7; H, 3.2; N, 8.1; Pb, 44.9.
periodate (0.12 g, 0.6 mmol) was added portionwise to a stirred
mixture of dihydroxyimidazolidine 14b (0.3 g, 1 mmol), CHCl3
(6 mL), and H2O (4 mL) at room temperature for 5 min. A poorly
soluble white compound was accumulated in the aqueous phase,
and the organic phase turned blueꢀgreen. The poorly soluble
compound disappeared after stirring of the reaction mixture for
1 h, and the chloroform layer turned brightꢀblue. The organic
layer was separated and the aqueous phase was extracted with
chloroform (1×5 mL). The combined organic solutions were
dried with Na2SO4. The solvent was removed on a rotary
evaporator, and the residue was crystallized by trituration
with hexane. The yield was 0.28 g (94%), m.p. 166—171 °C;
µ
= 1.73 µ (300 K). IR, ν/cm–1: 779, 837, 868, 985, 1025,
eff
B
Complex Ni(3b´)2•2H2O. Nickel sesquioxide Ni2O3 (1.25 g,
7.6 mmol) was added to a solution of 14a (0.33 g, 0.89 mmol) in
methanol (5 mL). The reaction mixture was stirred at ~20 °C for
two days and filtered. The solution was concentrated in vacuo,
the residue was dissolved in MeOH (10 mL), and H2O (10 mL)
was added. The solution was kept in an open flask in a thermoꢀ
stat at 20 °C. After 1 day, the gray precipitate that formed was
filtered off, the filtrate was concentrated, and the blue residue
was triturated with a mixture of hexane and benzene, resulting
in the formation of a blue powder, which was filtered off, washed
with diethyl ether, and recrystallized from a mixture of MeOH
and water. The yield was 0.2 g (53%). The complex is poorly
soluble in water and diethyl ether and is readily soluble in methaꢀ
nol and ethanol. IR, ν/cm–1: 775, 853, 878, 1050, 1097, 1140,
1170, 1217, 1286, 1370, 1392, 1461, 1511, 1622, 1728, 2981, 3435
br. Found (%): C, 46.4; H, 5.9; N, 14.0. C32H44N8NiO12•2H2O.
Calculated (%): C, 46.5; H, 5.9; N, 13.5.
1089, 1157, 1227, 1260, 1369, 1395, 1460, 1730, 2994, 3227.
Found (%): C, 52.8; H, 6.4; N, 18.9. C13H19N4O4. Calcuꢀ
lated (%): C, 52.9; H, 6.5; N, 19.0.
Complex Pb(K3e´)2•3MeOH. Compound 13d (0.5 g,
3.6 mmol) was added to a stirred solution of KOH (0.2 g,
3.6 mmol) in MeOH (9 mL). After 10 min, compound 2 (0.53 g,
3.6 mmol) was added. After 1 day, the reaction mixture (a paleꢀ
yellow suspension) was filtered, PbO2 (4.5 g, 18.8 mmol) was
added to the filtrate, and the mixture was stirred for one day and
filtered. The solvent was removed, THF (25 mL) was added to
the brightꢀblue residue, and the mixture was heated to 50 °C and
filtered. The filtrate was concentrated, the residue was dissolved
in MeOH (10 mL), toluene (5 mL) was carefully added along
the wall of the flask, and the mixture was kept in an open flask at
room temperature. The blackꢀblue precipitate that formed was
filtered off and washed with hexane. The yield was 1.03 g; µ
=
eff
2.35 µB (300 K). IR, ν/cm–1: 803, 898, 1018, 1045, 1166, 1212,
1352, 1452, 1581, 2983, 3405. MS, m/z (Irel (%)): 487 (5), 437
(6), 376 (10), 306 (31), 291 (63), 267 [3e´ + H+ + 1]– (9), 266
Ethyl 3ꢀ(4,4,5,5ꢀtetramethylꢀ3ꢀoxidoꢀ1ꢀoxylꢀ4,5ꢀdihydroꢀ
1Hꢀimidazolꢀ2ꢀyl)ꢀ1Hꢀpyrazoleꢀ5ꢀcarboxylate (3c). Sodium
3c
3e•H2O
4
10
14a
15
16•C7H8
P21/c
10.188(5)
6.781(3)
P21/n
P21/c
P21/c
P212121
11.018(2)
23.499(5)
7.4085(15)
P21/n
C2/c
8.9902(10)
11.5567(13)
14.0991(15)
13.173(5)
12.041(4)
12.879(4)
12.531(6)
9.317(4)
10.260(4)
7.237(16)
14.765(3)
12.938(3)
25.498(8)
9.129(3)
22.635(6)
21.993(10)
102.340(10)
99.111(2)
110.972(7)
111.678(10)
—
93.541(3)
106.721(8)
1484.2(11)
4
1446.4(3)
4
1907.6(11)
4
1113.2(8)
4
1918.2(7)
4
1379.9(5)
4
5046.0(2)
8
1.322
0.100
1.90—23.25
6113
1.310
0.105
2.29—23.24
6121
1.318
1.237
0.085
1.75—23.40
4743
1.283
0.099
1.73—23.30
8119
1.426
0.113
2.10—23.29
9991
1.194
0.081
1.67—23.30
17633
3605
0.096
2.37—23.33
8157
2129
2071
2750
1628
2746
1975
0.1466
1142
0.0638
1708
0.0961
1273
0.0721
990
0.0364
2346
0.0656
2756
0.1510
2756
252
250
349
197
340
255
314
0.0740
0.1842
0.0401
0.0993
0.0553
0.1087
0.0465
0.0799
0.0395
0.0889
0.0373
0.1001
0.1313
0.3721
0.1361
0.2373
0.732
0.0484
0.1042
0.953
0.1361
0.1382
0.757
0.0857
0.0923
0.840
0.0509
0.0945
1.014
0.0460
0.1068
0.753
0.1485
0.3839
2.556

2180
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 9, September, 2005
Tretyakov et al.
[3e´ + H+]– (62), 251 (100), 233 (23). Found (%): C, 32.7;
H, 4.0; N, 11.9; Pb, 23.8. C22H26K2N8O8Pb•3MeOH. Calcuꢀ
lated (%): C, 32.9; H, 4.2; N, 12.3; Pb, 22.7.
•H2O (0.9 g, 3.4 mmol) was added to a stirred suspension of 12a
(0.29 g, 1.7 mmol) in water (4.5 mL). The reaction mixture was
stirred for two days. The resulting paleꢀyellow solution was transꢀ
ferred into a beaker, CHCl3 (12 mL) was added, the reaction
mixture was carefully neutralized with NaHCO3 until eliminaꢀ
tion of CO2 ceased, and NaIO4 (0.58 g, 2.7 mmol) was added
portionwise for 1 h. The reaction mixture was stirred for 20 min,
the organic phase was separated, and the aqueous phase was
extracted with CHCl3 (1×20 mL). The combined organic soluꢀ
tions were dried with Na2SO4 and filtered. Heptane (20 mL) was
added to the filtrate, and the solution was concentrated to 20 mL.
The darkꢀblue crystals that formed were filtered off. The yield
was 0.3 g (47%). The compound decomposes at 195—210 °C;
Monopotassium 3ꢀ(4,4,5,5ꢀtetramethylꢀ3ꢀoxidoꢀ1ꢀoxylꢀ4,5ꢀ
dihydroꢀ1Hꢀimidazolꢀ2ꢀyl)ꢀ1Hꢀpyrazoleꢀ4,5ꢀdicarboxylate
(K3d″). A 10% aqueous KOH solution (20 mL) was added to a
stirred suspension of 13c (3.43 g, 18.6 mmol) and 2 (2.76 g,
18.6 mmol) in MeOH (60 mL). The resulting solution was stirred
for 4 h, during which a white precipitate gradually formed. The
precipitate was filtered off, dissolved in water (10 mL), and
oxidized with PbO2 (15.0 g, 62.7 mmol). The solvent was disꢀ
tilled off, and the residue was washed with acetone, filtered off,
and recrystallized from an EtOH—toluene mixture. The yield
was 2.49 g, a darkꢀviolet powder. IR, ν/cm–1: 801, 837, 854,
874, 1117, 1171, 1221, 1289, 1355, 1400, 1429, 1458, 1505,
1581, 2986, 3174, 3448, 3584. Found (%): C, 31.9; H, 3.1;
N, 11.3. According to the results of chelate titration, the sample
contained no Pb. MS, m/z (Irel (%)): 311 [3d´ + 2H+ + 1]–
(15.0), 310 [3d´ + 2H+]– (100), 294 (31), 266 (60), 250 (20).
The most probable composition of K33d´•2H2O was
µ
= 2.42 µ (300 K). IR, ν/cm–1: 844, 866, 988, 1024, 1082,
eff
B
1139, 1162, 1211, 1344, 1373, 1421, 1451, 2988, 3267. Highꢀ
resolution MS. Found: m/z 378.2009 [M]+. C17H26N6O4. Calꢀ
culated: M = 378.2015. MS, m/z (Irel (%)): 378 (2), 249 (14),
248 (19), 84 (100), 69 (41), 56 (18). Found (%): C, 52.6;
H, 7.3; N, 21.7. C17H26N6O4•0.5H2O. Calculated (%):
C, 52.7; H, 7.0; N, 21.7.
C
12H12K3N4O6•2H2O. Calculated (%): C, 31.2; H, 3.5; N, 12.1.
A solution of H2SO4 (0.67 g, 6.8 mmol) in EtOH (10 mL)
The reaction of 12a and NaIO4 in a molar ratio of
1 : 2 afforded a blueꢀgreen product, which was suspended
in ethyl acetate (~20 mL). The poorly soluble byꢀproduct
was filtered off. The filtrate was concentrated and recrysꢀ
tallized from a CH2Cl2—heptane mixture. The yield of 4
was 0.3 g (17%). The weight of the byꢀproduct was 0.56 g.
Crystallization of the byꢀproduct from a mixture of CH2Cl2
and toluene afforded crystals of 5ꢀ(4,4,5,5ꢀtetramethylꢀ3ꢀ
oxidoꢀ4,5ꢀdihydroꢀ1Hꢀimidazolꢀ2ꢀyl)ꢀ3ꢀ(4,4,5,5ꢀtetramethylꢀ
3ꢀoxidoꢀ1ꢀoxylꢀ4,5ꢀdihydroꢀ1Hꢀimidazolꢀ2ꢀyl)ꢀ1Hꢀpyrꢀ
azole (16).
Xꢀray diffraction study. Xꢀray diffraction data sets for all
compounds were collected on a Smart Apex diffractometer
(λMoꢀKα, graphite monochromator). The structures were solved
by direct methods and refined by the fullꢀmatrix leastꢀsquares
method using the SHELXTL program package. The positions of
a number of H atoms were located from difference electron
density maps. The positions of the other H atoms were calcuꢀ
lated geometrically and refined using a riding model (a rigidꢀ
body approximation).
was added dropwise to a solution of the product (1.42 g, 3.1 mmol
with respect to K33d´•2H2O) in EtOH (20 mL). The precipitate
was filtered off, sodium formate (0.48 g) was added to the filꢀ
trate, and the filtrate was concentrated. Ethanol (~50 mL) was
added to the residue, the insoluble precipitate was filtered off,
and the filtrate was concentrated. The residue was dissolved in a
minimum amount of EtOH (~15 mL) with slight heating
(~40 °C) and kept at 0 °C for one week. The precipitate that
formed was composed of paleꢀbrown crystals and a yellow powꢀ
der. The precipitate was filtered off, washed with diethyl ether,
and dried in air. Xꢀray diffraction study of the crystals demonꢀ
strated that they consist of the ions of compound 15. The filtrate
was concentrated. The residue was dissolved in a minimum
amount of water (~5 mL) with slight heating (~40 °C) and kept
at 0 °C for three days. The redꢀviolet powdered precipitate that
formed was filtered off and washed with acetone. The yield was
150 mg (13%); µ = 1.72 µ (300 K). IR, ν/cm–1: 781, 798,
874, 1003, 1127, 1177, 1250, 1329, 1368, 1418, 1481, 1529,
1575, 1613, 2852, 2922, 2992, 3251. MS, m/z (Irel (%)): 312
[3d″ + 2] (2.3), 311 [3d″ + 1]– (15.2), 310 [3d″]– (100), 266 (86),
222 (18). Found (%): C, 40.8; H, 4.1; N, 15.9. C12H14N4O6K.
Calculated (%): C, 41.3; H, 4.0; N, 16.0. The successive reacꢀ
tions of K3d″ with NaH and EtI in DMF afforded 3b (TLC
data). The reaction of K3d″ with an equivalent amount of H2SO4
in EtOH yielded a diamagnetic yellowꢀbrown product.
3ꢀ(4,4,5,5ꢀTetramethylꢀ3ꢀoxidoꢀ1ꢀoxylꢀ4,5ꢀdihydroꢀ1Hꢀ
imidazolꢀ2ꢀyl)ꢀ1Hꢀpyrazoleꢀ5ꢀcarboxylic acid (3e) was syntheꢀ
sized analogously to K3d″ from Pb(K3e´)2 (0.24 g, 0.26 mmol).
The crude product was recrystallized from a CH2Cl2—toluene
mixture. The yield was 60 mg (43%), darkꢀblue needleꢀlike crysꢀ
tals; µ = 1.73 µ (300 K). IR, ν/cm–1: 770, 789, 848, 997,
1019, 1091, 1138, 1174, 1227, 1284, 1374, 1400, 1472, 1639,
1722, 2992, 3275, 3390. Found (%): C, 47.2; H, 5.9; N, 18.7.
C11H15N4O4•H2O. Calculated (%): C, 46.3; H, 6.0; N, 19.6.
The successive reactions of 3e with NaH and EtI in DMF proꢀ
duced 3с (TLC data).
eff
B
Crystals suitable for Xꢀray diffraction study were grown by
crystallization of the compounds from the following solvents
and their mixtures (v/v): 1a, acetone—heptane; 1c, C6H6—hepꢀ
tane (1 : 1); 1d, diethyl ether—heptane; 3a, toluene;
3с, CH2Cl2—heptane (1 : 1); 3e•H2O, MeOH—H2O;
4, CH2Cl2—heptane; and 10, toluene—heptane (1 : 2).
Principal crystallographic characteristics and details of Xꢀray
diffraction studies are given in Table 1.
This study was financially supported by the Russian
Science Support Foundation, The Russian Academy of
Sciences, the Siberian Branch of the Russian Academy of
Sciences, the Russian Foundation for Basic Research
(Project Nos 04ꢀ03ꢀ08002 and 05ꢀ03ꢀ32305), the Counꢀ
cil on Grants of the President of the Russian Federation
(Program for State Support of Leading Scientific Schools
of the Russian Federation, Grant, NShꢀ2298.2003.3), and
the Bruker.
eff
B
Bis[3,5ꢀ(4,4,5,5ꢀtetramethylꢀ3ꢀoxidoꢀ1ꢀoxylꢀ4,5ꢀdihydroꢀ
1Hꢀimidazolꢀ2ꢀyl)]ꢀ1Hꢀpyrazole (4). The compound 2•H2SO4•

Pyrazolylꢀsubstituted nitronyl nitroxides
Russ.Chem.Bull., Int.Ed., Vol. 54, No. 9, September, 2005
2181
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Cryst., 1999, 334, 109.
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Received May 18, 2005;
in revised form July 8, 2005