Tautomerism of Aza cycles: IV. Tautomeric structure of 4,5-dihydropyrazol- 5-one annelated on bond C3-C4 with piperidine cycle, and its three hydrochlorides

Article abstract of DOI:10.1134/S1070363214030219

5-Methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-3-one has been synthesized and shown to exist in crystal as zwitterionic structure with the proton localized on the nitrogen atom in the piperidine ring and negative charge delocalized ove

Full text of DOI:10.1134/S1070363214030219

ISSN 1070-3632, Russian Journal of General Chemistry, 2014, Vol. 84, No. 3, pp. 531–544. © Pleiades Publishing, Ltd., 2014.
Original Russian Text © B.I. Buzykin, A.T. Gubaidullin, V. N. Nabiullin, A.F. Saifina, 2014, published in Zhurnal Obshchei Khimii, 2014, Vol. 84, No. 3,
pp. 473–487.
Tautomerism of Aza Cycles: IV.1 Tautomeric Structure
of 4,5-Dihydropyrazol-5-one Annelated on Bond C3–C4
with Piperidine Cycle, and Its Three Hydrochlorides
B. I. Buzykin, A. T. Gubaidullin, V. N. Nabiullin, and A. F. Saifina
Arbuzov Institute of Organic and Physical Chemistry, Kazan Research Center, Russian Academy of Sciences,
ul. Arbuzova 8, Kazan, Tatarstan, 420088 Russia
e-mail: buz@iopc.ru
Received March 28, 2013
Abstract—5-Methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-3-one has been synthesized
and shown to exist in crystal as zwitterionic structure with the proton localized on the nitrogen atom in the
piperidine ring and negative charge delocalized over the pyrazololate fragment. The structure of 2 : 1, 1 : 2, and
2 : 3 hydrochlorides derived from the title compound has been determined by X-ray analysis.
DOI: 10.1134/S1070363214030219
Among prototropic tautomeric systems, pyrazol-5-
one derivatives have been studied in most detail. Apart
from ketone (A) and enol tautomers (B), NH tautomer
(C) was detected for some pyrazol-5-one derivatives
[2–4]. This may be interpreted assuming concurrent
keto–enol and imine–enamine tautomerism. In
addition, NH tautomer (C) may be presumed to result
from proton transfer from the OH group of tautomer B
to produce zwitterionic structure D (an orbital isomer
of C [5–7]). The properties of the NH tautomer should
be determined by a large contribution of canonical
structure D to the ground states, which should be
reflected in its spectral and structural parameters. For
instance, IR absorption bands typical of ammonium
ions (2700–2400 cm–1) should appear, whereas no
bands typical of carbonyl stretching vibrations (1700–
1650 cm–1) should be observed [8]. These assumptions
are consistent with numerous IR spectral data for
pyrazol-5-ones (for detailed analysis of published data,
see [9]). However, the possibility for easy π-electron
delocalization [10] in tautomer D considerably reduces
its energy preference over orbital isomer C, whereas
the observed reduction of the OH, NH, and C=O
stretching vibration frequencies is usually attributed to
hydrogen bonding [9]. It should be noted that both
these structures are capable of forming hydrogen
bonds; therefore, additional experiments are necessary
to confirm the ability of the OH group in tautomer B to
act as intramolecular proton donor with respect to the
nitrogen atom.
N
N
N
+N
N
O
N
O
N
O
N
O_
H
H
H
R
R
R
R
A
B
C
D
Taking into account that the stability of different
tautomers is determined by their acid–base properties
(the most stable tautomer is the weakest acid) [11, 12],
we presumed that fusion of a piperidine [13],
dihydropyrrole, or other highly basic heterocycle to
pyrazol-5-one should lead to labile proton localization
on the most basic nitrogen atom. For this purpose, we
have synthesized piperidine-fused pyrazol-5-one from
1-methyl-4-oxopiperidine-3-carboxylate Ia and phenyl-
hydrazine [14]. The resulting 5-methyl-2-phenyl-
1
For communication III, see [1].
531

532
BUZYKIN et al.
Scheme 1.
Ph
N
Ph
Ph
O
O
N
N
N
N
N
_
O_
O
PhNHNH2
O
R
O
H
+
+
N
N
N
N
H
H
Me
Me
Me
Me
Ia
IIa
III
IV
R = Me or Et.
3,3a,4,5,6,7-hexahydro-2H-pyrazolo[4,3-c]pyridin-3-
one (IIa) should exist as a zwitterionic structure III or
IV with protonated nitrogen atom of the piperidine
fragment rather than traditional CH-, OH-, or NH-
pyrazole tautomers. Depending on the nature of sub-
stituents in different molecular fragments, such pyra-
zolopiperidines could be expected to exist as zwitter-
ionic orbital isomers [5–7] with the anionic center
either localized on the pyrazole nitrogen or oxygen
atom or, more probably, essentially delocalized over
the pyrazololate fragment (structure IV, Scheme 1).
some other compounds which were detected by TLC.
Compounds V and VI predominated among the
products, and the yield of hydrazone VII was con-
siderably lower. We succeeded in isolating compounds
V–VII in the pure state [14, 22–24]; in addition, 3a,5-
dimethyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-
pyrazolo[4,3-c]pyridin-3-one (VIII) and methyl (4Z)-
4-(2-phenylhydrazono)-3,4-dihydro-2H-pyrrole-5-
carboxylate (IX) [25] were identified by spectral
methods. The other products were detected only by
thin-layer chromatography. The structure of V–IX will
be the subject of the next communication of this series.
5-Acyl, 5-aryl, and 5-pyridinylmethyl analogs of
pyrazolopiperidine IIa have been successfully
synthesized [15–19] and even proposed for use as
biologically active compounds and medicinal agents.
The synthesis of 5-methyl-6-phenyl derivatives was
also reported [19], and these compounds were assigned
(without rigorous substantiation) the structures of all
three known CH [13, 15, 16, 19], NH [4, 15–18, 20],
and OH tautomers [15, 19, 21]. In view of ambiguity
of published data on the structure of hexahydro-
pyrazolo[4,3-c]pyridinone derivatives, in the present
work we examined the condensation of keto ester Ia
with phenylhydrazine in more detail.
Pyrazolopiperidine IIa was isolated as finely
crystalline material when ester Ia (R = Me or Et) was
carefully mixed with phenylhydrazine in methanol or
benzene and the mixture was then kept at room or
lower temperature. Compound IIa is soluble in water
and acetic and trifluoroacetic acids, very poorly
soluble in methanol and other alcohols, and insoluble
in nonpolar solvents. Crystalline compound IIa can be
stored for many years without appreciable decom-
position (according to the IR data). It reacts with acids
to form the corresponding salts; in particular, three
hydrochlorides X–XII with different compositions
were obtained from IIa and HCl (Scheme 2).
The reaction of phenylhydrazine with keto ester Ia
under standard conditions of synthesis of pyrazol-5-
ones (heating in boiling alcohols or benzene) resulted
in the formation of a complex mixture consisting of 5–
7 products among which no pyrazolopiperidine IIa
was detected [14, 22–24]. When a mixture of Ia (R =
Me) and phenylhydrazine was heated for 5 min in
boiling methanol, propan-2-ol, or benzene, the pro-
ducts were bis{5-methyl-3-oxo-2phenyl-3,3a,4,5,6,7-
hexahydro-2H-pyrazolo[4,3-c]pyridin-3-yl}methane
(V), 5-methyl-2-phenyl-3,5,6,7-tetrahydro-2H-
pyrazolo[4,3-c]pyridin-3-one (VI), (3Z)-1-methyl-3-
(2-phenylhydrazinylidene)pyrrolidin-2one (VII), and
The IR spectra of a crystalline sample of IIa (in
KBr or mineral oil) lacked absorption bands assignable
to carbonyl stretching vibrations and absorption above
3000 cm–1, but a strong hump was observed in the
+
region 2100–2600 cm–1 typical of N–H stretching
vibrations. Analogous absorption was observed in the
spectra of hydrochlorides X–XII and ester Ia
hydrochloride (XIII); the structure of the latter was
unambiguously determined by X-ray analysis (Fig. 1).
Hydrochloride XIII in crystal has enol structure with
the intramolecular hydrogen bond OH···O=C [H4···O8
1.86 Å, ∠O4H4O8 150(3)°]. The C3–C4 and C4–O4
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

TAUTOMERISM OF AZA CYCLES: IV.
533
Scheme 2.
Ph
Ph
Ph
N
N
N
N
NH
N
PhNHNH2
O
O
N
+
+
O
Ia
a, b
N
N
O
N
Me
Me
N
N
Me
Ph
V
VI
Ph
NH
VII
Ph
N
N
N
O
O
Me
+
+
Me
O
N
N
Me
VIII
IХ
а, MeOH, 65°C; b, i-PrOH, 80°C.
bond lengths in XIII indicate a classical version of
keto–enol tautomerism (C=C 1.340 Å, C–O 1.333 Å
[26]). The acidic proton is localized on the pyramidal
nitrogen atom in the piperidine ring, the degree of
pyramidality [27] being CPN 0.595.
By reacting phenylhydrazine hydrochloride with
ester Ia hydrochloride we obtained pyrazolopiperidine
IIa salt with the same melting point (mp 225–227°C).
However, this salt was not a simple 1 : 1 hydro-
Molecules XIII in crystal are linked through
hydrogen bonds of different types. The hydrogen bond
N–H···Cl links the N1 atom and chloride counterion.
Non-classical hydrogen bonds C–H···O between H9 in
the methoxy group and O4 in the hydroxy group, as
well as between H7 and O8 carbonyl oxygen atom, give
rise to layers parallel to the a0c plane (Fig. 2). The
layers are linked to form three-dimensional network
through C–H···Cl bonds between methylene hydrogen
atoms in the piperidine ring and Cl1.
In the 1H NMR spectra of pyrazolopiperidine IIa in
D2O and CD3OD, only signals from aromatic and
methyl protons were observed clearly, presumably as a
result of exchange processes and conformational
transformations. Signals from methylene protons
appeared as broadened singlets, which were sometimes
poorly resolved into triplets. No labile proton signal
was detected. The above IR and 1H NMR data suggest
that compound IIa in crystal and in solution (D2O,
CD3OD) exists as zwitterion IV. We failed to obtain
crystals of IIa suitable for X-ray analysis by crys-
tallization from D2O or CD3OD.
Fig. 1. Structure of hydrochloride XIII in crystal according
to the X-ray diffraction data. Non-hydrogen atoms are shown
as thermal vibration ellipsoids with a probability of 50%;
hydrogen atoms are shown by spheres of arbitrary fixed
radius. Principal bond lengths and bond (Å) and torsion
angles (deg): O4–H4 0.85(4), O4–C4 1.339(3), N1–H1 0.81(2),
N–C 1.485(3), C3–C4 1.345(3), C3–C8 1.450(3), O8–C8 1.226
(3), O9–C8 1.340(2); C2N1C6 112.7(2), C2N1C7 111.5(2),
C6N1C7 112.0(2), C5C4O4 125.0(2), C8O9C9 116.4(2), C4O4H4
103(2); C3C4O4H4 –9(2), C4C3C8O8 –1.3(3), C4C3C2N1 15.7
(3), C4C5C6N1 –47.9(2).
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

534
BUZYKIN et al.
Fig. 2. Layered structure formed by molecules of hydrochloride XIII in crystal via C–H···O hydrogen bonding (view along the 0b
crystallographic axis; hydrogen bonds are shown as dotted lines; chloride ions are not shown).
chloride as reported in [13]. According to the results of
our X-ray diffraction study, it has a composition of
2 : 3 (hydrochloride X) [28]. The reaction of Ia·HCl
with phenylhydrazine gave a different salt whose
decomposition was estimated at 2 : 1 (XI, mp 173–
175°C). Dissolution of X in concentrated aqueous HCl,
followed by removal of the acid, afforded one more
salt XII with a composition of 1 : 2, mp 163–165°C
(Scheme 3).
All three hydrochlorides X–XII are stable crys-
talline compounds readily soluble in water, DMSO,
and acetic and trifluoroacetic acids. Determination of
the melting points of X–XII by the capillary method
gave different values: X, 220–221°C; XI, 173–175°C;
XII, 225–227°C (each with decomposition), whereas
all three salts melted almost in the same temperature
range (160–165°C) on a Boëtius hot stage. Pre-
sumably, in the latter case, excess HCl is removed
Scheme 3.
Cl_
H
Me
N+
H
Ph
O
O
H
Me
N
N
PHNHNH2
O
Cl _
H
O_
O
H
N+
N
N
N+
Me
Me
Me
ХI
ХIII
Cl_
Me
N+
H
H
Ph
Ph
H
N+
N+
N
N
HCl
Cl_
Cl_
H
H
O_
O
O
PHNHNH2 HCl
Cl_
N+
Me
Cl_
N+
N
H
N+
Me
H
Ph
H
Х
ХII
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

TAUTOMERISM OF AZA CYCLES: IV.
from crystalline samples of X and XII at a temperature
535
lower than the melting point.
Like hydrochloride XIII, the IR spectra of X–XII
displayed a broadened absorption band in the region
2700–2500 cm–1, which corresponds to N+–H stretch-
C4B
1
ing vibrations. The IR and H NMR spectra of X–XII
are fairly similar. Unfortunately, the salt character of
compounds X–XII restricts the range of solvents
1
suitable for recording their H NMR spectra, whereas
protic solvents initiate exchange processes, which
reduces informativeness of the spectra.
Judging by the 13C NMR spectra of freshly prepared
solutions of pyrazolopiperidine IIa in trifluoroacetic
acid [δC, ppm: 19.0 (C8, CH2), 43.2 (NMe), 48.9 (C4,
CH2), 51.3 (C7, CH2), 95.6 (C3a), 124.6 (Cm, Ph), 130.1
(Co, Ph), 131.2 (Cp, Ph), 131.7 (C8a), 141.9 (Ci, Ph),
153.2 (C3)], this compound in acid solution is
represented by dication with protons attached to the
N1, N6, and O3 atoms; such dication was identified in
crystalline hydrochloride X.
C4A
N6A
C7A
Fig. 3. Structure of independent molecules of hydrochloride
X in crystal. Non-hydrogen atoms are shown as thermal
vibration ellipsoids with a probability of 50%; hydrogen
atoms are shown by spheres of arbitrary fixed radius.
Hydrogen bonds are shown with dotted lines.
The site of protonation of multicenter bases is
determined by a number of factors, including the
nature of substituents in the basic fragment and
predominant tautomer structure. As a rule, it is difficult
to identify the site of protonation in such compounds
by spectral methods. Therefore, the structure of
hydrochlorides X–XII in crystal was unambiguously
assigned only by X-ray analysis. The position of
hydrogen atoms attached to heteroatoms in molecules
X–XII was determined independently from the
difference electron density series.
the pyrazole and benzene rings in molecule XA is 9.0°.
This may be due to formation of two intramolecular
hydrogen bonds between H1A1 and N1A (N1A1···N1A
2.53 Å, ∠C1A1H1A1···N1A 101°) and between H1A5 and O3A
(H1A5···O3A 2.18 Å, ∠C1A5H1A5O3A 126°) (Fig. 3), as well as
due to conjugation between the electron systems of
both fragments. The dihedral angle between the
corresponding planes in the second cation of X is
15.8°.
The N6 nitrogen atom in five pyrazolopiperidinium
cations of three hydrochlorides X–XII always bears a
proton, which confirms our assumption that N6 is more
basic than the other basic centers in molecule IIa.
Cations XA and XB in crystal are linked to the
counterions through N–H···Cl hydrogen bonds involv-
ing hydrogen atoms on the nitrogen atoms in both
pyrazole and piperidine rings [N1AH1A···Cl2 2.46(8) Å,
∠N1AH1ACl2 150(7)°, (1/2 + x, 1/2 – y, 1/2 + z);
N1BH1B···Cl1 2.15(7)Å, ∠N1BH1BCl1 160(5)°, (1/2 + x,
1/2 – y, –1/2 + z); N6A–H6A···Cl3 2.05(5) Å, ∠N6AH6ACl3
174(2)°, (3/2 – x, 1/2 + y, 1/2 – z); N6B–H6B···Cl2
2.19(6) Å, ∠N6BH6BCl2 163(2)°, (1/2 – x, 1/2 + y, 1/2 – z)].
The independent part of a unit cell of 2 : 3
hydrochloride X includes zwitterion IV protonated at
the N1 atom (molecule XA), dication XB with three
protons attached to N1, N6, and O3, and three chloride
ions as counterions (Fig. 3). Both cations XA and XB
are linked to each other through the classical
intermolecular O3BH3B···O3A– hydrogen bond, so that the
distances O3B···H3B and O3A···H3B become fairly leveled
[O3B–H3B 1.10(9), O3B···O3A 2.406(6), H3B···O3A
1.32(8) Å; ∠O3BH3BO3A 168(8)°].
Chloride ions in the crystal of sesquihydrochloride
X also form hydrogen bonds C–H···Cl with hydrogen
atoms of the methyl group and benzene and piperidine
ring with the distances ranging from 2.73 to 2.86 Å
and angles ranging from 140° to 160°; these bonds in
turn give rise to bilayers parallel to the a0c plane. The
π···π contacts between the pyrazole and benzene rings
Despite steric hindrances induced by closely
located H1A in the pyrazole fragment and H1A1 in the
benzene ring the dihedral angle between the planes of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

536
BUZYKIN et al.
Fig. 4. A fragment of three-dimensional network formed by molecules of hydrochloride X (rod representation) in crystal.
Intermolecular interactions are shown with dotted lines.
in the symmetry-related ions XA and XV provide
additional stabilization of the bilayers. The set of the
aforesaid intermolecular interactions is responsible for
the formation of three-dimensional network in the
crystal structure of hydrochloride XB (Fig. 4).
linked in turn to produce three-dimensional network
through the following C–H···N and C–H···O
hydrogen bonds: H1A4···N1B 2.74 Å, ∠C1A4H14N1B 133°,
(2 – x, 1/2 + y, 1 – z); C1B4H1B4···N1A 2.64 Å, ∠C1B4H1B4N1A
137°, (1 – x, –1/2 + y, 2 – z); H5B1···N2A 2.70 Å,
∠C5BH5B1N2 162°; H5B2···O3A 2.41 Å, ∠C5BH5B2O3A 122°,
A
(–1 + x, y, z); H5A2···O3B 2.53 Å, ∠C5AH5A2O3B 116°, (1 +
The independent part of a unit cell of 2 : 1
hydrochloride XI comprises a chloride ion and two
molecules XIA and XIB that are linked to each other
through the intermolecular hydrogen bond O3A–
H3A···O3B with the following parameters: H3A···O3B
1.56(5) Å, ∠O3AH3AO3B 151(7)° (1 + x, y, z) (Fig. 5).
Molecule XIB has zwitterionic structure IV, and
molecule XIA is zwitterion IV protonated at the
oxygen atom.
x, y, z); H7A1···O3B 2.58 Å, ∠C7 H7 1O3B 151°; H7B1···O3A
A
A
2.69 Å, ∠C7BH7B1O3A 148°. Additional stabilization of the
three-dimensional network is achieved via C–H···π
interactions between the H163 atom of the methyl group
and benzene ring (PhB), between H166 in the methyl
group of the second independent molecule and PhA,
and between H51 in the tetrahydropyridine ring and
pyrazole ring (N1A–C9A).
The benzene ring plane in both XIA and XIV is
turned with respect to the pyrazole ring plane through
dihedral angles of 22.5° and –19.7°, respectively.
These angles are larger by almost 10° than those in the
corresponding (with account taken of protonation)
molecules XB and XA. As in the latter, the observed
arrangement of the benzene and pyrazole rings may be
rationalized by the formation of hydrogen bonds
O3···H15 [H1A5···O3A 2.26 Å, ∠C1A5H1A5O3A 120°; H1B5···O3B
2.38 Å, ∠C1B5H1B5O3B 118°] and N1···H11 [C1A1H1A1···N1A
2.41 Å, ∠C1A1H1A1N1A 100°; H1B1···N1B 2.46 Å,
∠C1B1H1B1N1B 102°] (Fig. 5).
The crystal structure of dihydrochloride XII is
represented by one pyrazolopiperidine IIa dication and
two chloride ions as external counterions (Fig. 7).
Here, the asymmetric part of the unit cell contains only
one independent molecule. The three protons in the
dication are attached to different heteroatoms (N1, N6,
and O3), which indicates that no C3aH tautomer is
formed in the crystal structure of IIa. The dihedral
angle between the benzene and pyrazole ring planes in
dication XII is 31.5° and is the largest among the
examined pyrazolopiperidine IIa salts. As in the above
cases, the formation of weak intramolecular hydrogen
bond C15–H15 ···O3 (H···O 2.37 Å, ∠C15H15O3 113°)
hinders rotation by a larger angle.
Unlike hydrochloride X, chloride ion in the crystal
structure of XI is involved only in hydrogen bonds
N6–H6···Cl [H6A···Cl1 1.94(2) Å, ∠N6AH6ACl1 164(2)°,
(1 + x, y, 1 + z); H6B···Cl1, 1.97(2) Å, ∠N6BH6BCl1
173(2)°]. These bonds are orthogonal to the
intermolecular O3A–H3A···O3B bonds which link
molecules XIA and XIB together. A combination of
intermolecular hydrogen bonds N–H···Cl and
O–H···O leads to formation of zigzag chains of mole-
cules XI in crystal (Fig. 6). These zigzag chains are
Analysis of intermolecular interactions in the
crystal of dihydrochloride XII also revealed various
hydrogen bonds (OH···Cl, NH···Cl, CH···Cl) and
π···π contacts. The dication is linked to one chloride
ion (Cl2) by the hydrogen bond with the hydroxy
hydrogen atom (H3) [H3···Cl2 2.00(4) Å,
∠O3H3Cl2 174(4)°]. The second chloride ion (Cl1) is
involved in hydrogen bonds with both H1 in the
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

TAUTOMERISM OF AZA CYCLES: IV.
537
Fig. 6. Zigzag chains formed by hemihydrochloride XI
molecules in crystal via N–H···Cl and O–H···O hydrogen
bonds (view approximately along the 0a crystallographic
axis). Hydrogen bonds are shown with dotted lines.
bond (1.210 Å) [26]. The N1–N2 bond in all cations is
similar or only slightly longer than the standard N–N
bond in pyrazole (1.366 Å; bond order 1.5) [26].
Protonation of the pyrazole ring does not lead to
significant extension of that bond, though its length
attains the maximum value in cation XIB having no
N+H group. The bond lengths in the benzene ring are
similar to those typical of benzene derivatives
containing electron-withdrawing groups [26].
Fig. 5. Structure of hemihydrochloride XI in crystal
according to the X-ray diffraction data. Non-hydrogen
atoms are shown as thermal vibration ellipsoids with a
probability of 50%; hydrogen atoms are shown by spheres
of arbitrary fixed radius. Hydrogen bonds are shown with
pyrazole fragment and H6 (N+H) in the tetrahydro-
pyridine ring [H1···Cl1 2.16(4) Å, ∠N1H1Cl1 170(4)°,
(1/2 – x, 1/2 + y, 1/2 – z); H6···Cl1 2.11(4) Å,
∠N6H6Cl1 163(3)°]. Stacks formed by dications XII
are linked to each other through hydrogen bonds
C–H···Cl with participation of both chloride ions (Cl1
and Cl2). Insofar as the number of chlorine atoms in
crystals of XII is fairly large, hydrogen bonds formed
by chloride ions (in combination with other inter-
molecular interactions) give rise to three-dimensional
H-bond network (Fig. 8). In addition, stacking
interactions between the pyrazole (N1–C9) and benzene
rings (C10–C15) of the symmetry-related dications are
observed.
The bond angles in the pyrazole rings of X–XII
approach the corresponding standard values for azoles.
However, the N2N1C9 angle in cations XIA and XIB is
appreciably smaller, and the N1N2C3 angle is larger,
than in cations X and XII where the pyrazole ring is
not protonated. The O3C3N2 angle in all cations X–XII
is larger than O3C3C4, which may be due to
intramolecular hydrogen bonding between O3 and H15
in the benzene ring. The bond angles in the benzene
rings differ insignificantly both within each benzene
fragment and in different pyrazolopiperidinone cations
X–XII.
The geometric parameters of the cations in hyd-
rochlorides X–XII are given in Table 1. It is seen that
the bond lengths and bond angles in the cations of salts
X–XII differ insignificantly. The bond lengths indicate
essential electron density delocalization in the pyrazole
ring, as well as conjugation with the O3 oxygen atom
and even with the benzene ring. The C3–O3 bond in all
cations is considerably shorter than the C–O bond in
alcohols (1.413 Å) and even somewhat shorter than in
phenol (1.362 Å) and enols (1.333 Å); on the other
hand, it is considerably longer than the standard C=O
Apart from rotation of the benzene ring with
respect to the pyrazole ring plane, acoplanarity of
cations X–XII is determined by conformation of the
tetrahydropyridine ring which adopts a flattened chair
structure. The C5, C4, C9, and C8 atoms of the
tetrahydropyridine ring lie almost in the pyrazole ring
plane, while the C7 and N6 atoms deviate from that
plane in opposite directions. The methyl group always
occupies equatorial position, and the hydrogen atom on
N6 is axial. The configuration of bonds at the N2 atom
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

538
BUZYKIN et al.
Cl1
Fig. 8. Packing of the dications and chloride ions in the
crystal structure of dihydrochloride XII (view along the 0a
crystallographic axis). Intermolecular interactions are shown
with dotted lines.
Fig. 7. Structure of dihydrochloride XII in crystal according
to the X-ray diffraction data. Non-hydrogen atoms are shown
as thermal vibration ellipsoids with a probability of 50%;
hydrogen atoms are shown by spheres of arbitrary fixed radius.
ray diffractometer (graphite monochromator, 20°C).
No drop in the intensity of three control reflections
was observed during data acquisition. A correction for
absorption was applied. The crystallographic data and
parameters of X-ray diffraction experiments and
structure refinement are given in Table 2.
in the pyrazole ring is planar in all cations X–XII, and
the N6 atom in the piperidine fragment is characterized
by pyramidal bond configuration with the degree of
pyramidality CPN [27] ranging from 0.477 to 0.695.
The structures were solved by the direct method
using SIR program [29] and were refined by the least-
squares procedure first in isotropic and then in
anisotropic approximation for all non-hydrogen atoms
using SHELXL software package [30]. Hydrogen
atoms in the hydroxy and ammonium groups in all
structures were visualized from the difference electron
density maps, and their positions were refined in
isotropic approximation. The coordinates of the other
hydrogen atoms were calculated on the basis of
stereochemical considerations and were refined
according to the riding model.
As already noted, hydrochlorides X–XII are stable
crystalline substances. Attempts to isolate free base IIa
from hydrochlorides X–XII were unsuccessful. As a
result, only complex mixtures containing compounds
V–IX and some others were obtained [14, 22, 23],
whose ratio depended on the isolation conditions. The
isolation procedures and structures of the transforma-
tion products of pyrazolopiperidine IIa will be re-
ported in detail in the next communication of this series.
EXPERIMENTAL
All calculations were performed with the aid of
MolEN [31] and WinGX [32], intermolecular inter-
actions were analyzed using PLATON [33], and the
structures were plotted using Mercury program [34,
35].
The H and 13C NMR spectra were recorded on
Bruker Avance-600 (600 MHz for H) and Bruker
1
1
Avance-400 spectrometers (400 MHz) using the
solvent signals as reference. The IR spectra were
measured on a Bruker Vector-22 instrument from
samples dispersed in mineral oil or pelleted with KBr
(the difference in the positions of bands did not exceed
±2 cm–1). The melting points were determined using a
Boëtius hot stage and a standard PTP melting point
apparatus. The mass spectra (electron impact) were
obtained on a Trace MS instrument. Samples were
injected as solutions in ethanol.
The coordinates and temperature factors of atoms in
the crystal structures of X–XIII were deposited to the
Cambridge Crystallographic Data Centre.
5-Methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-
pyrazolo[4,3-c]pyridin-3-one (IIa). Keto eester Ia
(R = Me, Et), 0.292 mol, was gradually added to a
solution of 3.16 g (0.292 mol) of freshly distilled
phenylhydrazine in 25 mL of anhydrous propan-2-ol,
and the mixture was left to stand overnight. The finely
crystalline solid was filtered off, washed with propan-
2-ol and (repeatedly) with methylene chloride, and
dried at room temperature. Yield 3.6 g (53%), light
The X-ray analyses of single crystals of X–XIII
were carried out at the Federal Joint Spectral Analytical
Center (Arbuzov Institute of Organic and Physical
Chemistry) on an Enraf–Nonius CAD-4 automatic X-
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

TAUTOMERISM OF AZA CYCLES: IV.
539
Table 1. Bond lengths and bond and torsion angles in the molecules of pyrazolopiperidinone hydrochlorides X–XII
X
XI
Parameter
XII
A
B
A
B
Bond lengths, Å
O3–H3
O3–C3
N1–N2
N1–H1
N1–C9
N2–C3
N2–C10
C3–C4
C4–C5
C4–C9
N6–C5
N6–C7
N6–C16
N6–H6
C7–C8
C8–C9
1.10(8)
0.941(19)
1.319(10)
1.381(10)
–
–
0.85(4)
–
1.280(6)
1.390(6)
0.70(7)
1.297(6)
1.368(5)
0.94(6)
1.310(10)
1.419(10)
–
1.305(4)
1.371(4)
0.90(4)
1.338(6)
1.368(6)
1.434(6)
1.392(6)
1.494(7)
1.355(7)
1.496(6)
1.504(7)
1.489(6)
1.00(6)
1.313(6)
1.359(6)
1.425(6)
1.405(6)
1.477(7)
1.377(7)
1.495(6)
1.428(8)
1.489(6)
1.00(6)
1.388(15)
1.419(14)
1.382(11)
1.374(16)
1.530(14)
1.351(16)
1.489(13)
1.536(19)
1.450(13)
1.06(2)
1.222(15)
1.341(14)
1.439(11)
1.377(16)
1.421(14)
1.452(15)
1.522(14)
1.445(17)
1.525(13)
1.06(2)
1.334(4)
1.352(4)
1.438(4)
1.395(4)
1.500(4)
1.369(4)
1.495(4)
1.485(5)
1.495(4)
1.03(4)
1.536(7)
1.505(7)
1.507(7)
1.496(6)
1.460(12)
1.486(14)
1.563(10)
1.505(14)
1.535(4)
1.477(4)
Bond angles, deg
C3O3H3
N2N1C9
N2N1H1
C9N1H1
N1N2C10
N1N2C3
C3N2C10
C5N6C7
C5N6C16
C7N6C16
C5N6H6
C7N6H6
C16N6H6
O3C3N2
O3C3C4
N2C3C4
C3C4C9
C3C4C5
C5C4C9
122(4)
117(4)
–
112(3)
–
108.1(4)
119(6)
109.1(4)
121.3(13)
128.4(13)
122.8(4)
107.5(4)
129.6(4)
116.0(4)
110.7(5)
114.2(5)
103.4(11)
106.5(11)
104.7(11)
122.1(5)
129.8(5)
108.1(4)
105.0(4)
131.3(5)
123.7(4)
102.1(7)
–
105.4(7)
–
107.9(3)
124(3)
133(6)
–
–
128(3)
121.2(4)
107.5(4)
131.3(4)
112.9(4)
110.4(4)
110.5(4)
107.7(10)
106.8(11)
108.2(11)
121.0(4)
131.7(5)
107.3(4)
107.6(5)
129.3(5)
123.0(4)
116.8(7)
111.1(7)
130.5(8)
110.3(13)
110.9(7)
113.1(9)
107.9(13)
104.5(12)
109.8(18)
118.9(10)
135.1(11)
105.9(9)
106.6(10)
129.3(9)
124.1(9)
119.0(7)
110.0(8)
130.9(8)
114.4(15)
113.0(7)
110.1(8)
104.6(12)
109.9(12)
104.1(18)
122.6(11)
129.2(10)
107.8(9)
102.4(10)
132.2(10)
124.8(9)
121.7(3)
108.3(3)
130.0(3)
111.9(3)
109.7(3)
110.5(3)
110(2)
108(2)
107(2)
118.5(3)
133.4(3)
108.0(3)
105.8(3)
130.8(3)
123.4(3)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

540
BUZYKIN et al.
Bond angles, deg
Table 1. (Contd.)
X
XI
Parameter
XII
A
B
A
B
N6C5C4
N6C7C8
C7C8C9
N1C9C4
N1C9C8
C4C9C8
N2C10C11
N2C10C15
109.1(4)
111.7(4)
106.9(5)
109.5(4)
124.2(5)
126.3(5)
120.6(4)
119.2(5)
109.3(4)
114.1(5)
109.5(5)
110.3(4)
126.2(5)
123.5(5)
120.4(5)
119.3(5)
109.0(7)
114.9(11)
108.4(8)
114.0(9)
121.7(9)
124.3(11)
120.4(6)
119.5(6)
109.4(8)
110.1(9)
111.5(8)
114.2(9)
126.1(8)
119.5(11)
117.9(6)
121.9(5)
107.9(3)
110.9(3)
108.9(3)
110.0(3)
125.6(3)
124.5(3)
119.5(3)
119.2(5)
Torsion angles, deg
H3O3C3N2
H3O3C3C4
C9N1N2C3
C9N1N2C10
N2N1C9C4
N2N1C9C8
H1N1N2C3
N1N2C3O3
N1N2C3C4
C10N2C3O3
C10N2C3C4
N1N2C10C11
N1N2C10C15
C3N2C10C11
C3N2C10C15
C7N6C5C4
C5N6C7C8
H6N6C7C8
C16N6C5C4
C16N6C7C8
O3C3C4C5
O3C3C4C9
N2C3C4C5
N2C3C4C9
C3C4C5N6
C9C4C5N6
C3C4C9N1
–172(4)
6(4)
–166(6)
19(6)
–
–148(3)
36(3)
–
–
–
0.8(6)
0.4(5)
4.8(15)
3.9(17)
–1.9(4)
179.9(3)
2.4(4)
178.9(5)
0.2(7)
178.7(5)
0.8(6)
171.5(11)
–2.6(18)
178.6(15)
–
–173.6(12)
–3.7(19)
–178.8(15)
–
–179.0(5)
–179(7)
177.0(5)
–1.5(6)
–0.8(9)
–179.3(5)
9.8(8)
–178.1(5)
–168(4)
177.4(4)
–1.3(5)
–0.8(8)
–179.4(5)
–16.1(8)
164.9(5)
161.9(5)
–17.2(8)
42.3(6)
–60.2(7)
54.3(15)
174.5(4)
169.3(5)
1.7(8)
–178.2(4)
–180(3)
–176.5(3)
0.7(5)
178.0(13)
–5.4(16)
14(2)
–174.9(13)
–2.4(16)
2(2)
1.5(6)
–169.7(13)
–14.9(14)
168.3(9)
148.7(12)
–28.1(17)
43.6(14)
–65.5(18)
51(2)
174.7(12)
19.2(14)
–166.3(10)
–157.6(12)
16.9(18)
–51.3(16)
63.9(17)
–53(2)
178.8(4)
30.2(6)
–149.9(4)
–147.6(4)
32.3(6)
50.8(4)
–67.8(4)
53(2)
–169.9(5)
–172.7(5)
7.6(8)
46.7(6)
–65.8(6)
52.6(16)
171.0(4)
170.1(5)
0.5(10)
–176.6(6)
178.8(5)
1.7(6)
169.5(13)
169.9(15)
–1(3)
–178.3(13)
–167.7(14)
0(3)
173.8(4)
169.5(3)
–2.8(8)
177.4(4)
–179.5(4)
0.7(5)
–176.9(5)
–179.7(5)
1.7(5)
179.3(18)
–176.5(15)
3.5(18)
172.1(16)
–171.5(17)
0.3(17)
167.8(5)
–15.5(7)
–1.2(7)
169.6(5)
–12.0(7)
–1.5(6)
165.9(16)
–14(2)
–166.6(17)
23(2)
162.7(4)
–17.5(6)
–1.9(5)
–1(2)
2(2)
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

TAUTOMERISM OF AZA CYCLES: IV.
541
Table 1. (Contd.)
X
XI
Parameter
XII
A
B
A
B
Torsion angles, deg
C3C4C9C8
C5C4C9N1
C5C4C9C8
N6C7C8C9
C7C8C9N1
C7C8C9C4
178.0(5)
–178.5(5)
0.7(9)
177.4(5)
179.8(4)
–1.4(8)
178.1(16)
179.4(14)
–2(3)
177.8(15)
174.9(16)
–10(3)
178.6(4)
178.2(4)
–1.2(6)
45.5(6)
41.5(7)
47(2)
–45(2)
44.4(4)
163.6(5)
–15.5(8)
166.3(5)
–12.4(7)
164.4(16)
–14(2)
–166.0(17)
19(2)
168.6(4)
–12.0(5)
beige powder, mp 143–145°C (decomp., PTP), 138–
143°C (decomp., Boëtius). The product was insoluble
in benzene, chloroform, carbon tetrachloride,
methylene chloride, diethyl ether, and acetonitrile, very
poorly soluble in DMSO, methanol, and propan-2-ol,
and soluble in water. IR spectrum (KBr), ν, cm–1:
3056, 3030, 2974, 2936, 2895, 2859, 2743 2685, 2576,
2474, 2341, 1609, 1588, 1579, 1537, 1493, 1453,
1420, 1380, 1351, 1318, 1275, 1240, 1161, 1152, 1128,
methanol. White crystalline powder, mp 219–221°C
(PTP). The filtrate was evaporated by half, and
colorless needles separated from the residue on storage
were filtered off, washed with methanol, and dried in
air. An additional portion of X, 1.25 g with mp 220–
222°C (decomp., PTP) was thus isolated. The two
portions of the product were combined and
recrystallized from a mixture of ethanol with water and
diethyl ether to obtain 1.8 g (42.4%) of X as colorless
needles with mp 220–222°C (decomp., PTP) or 164–
166°C (decomp., Boëtius); published data [13]: mp
224–225°C for 1 : 1 hydrochloride IIa·HCl. IR
spectrum (KBr), ν, cm–1: 3134, 3056, 3016, 2989,
2944, 2682, 2623, 2584, 2540, 2460, 2424, 2391,
2350, 1616, 1596, 1548, 1501, 1459, 1422, 1411,
1356, 1306, 1288, 1243, 1221, 1188, 1178, 1144, 1085,
1
1084, 1067, 1051, 1032, 1011, 996, 972. H NMR
spectrum, δ, ppm (J, Hz): in D2O: 7.50 d (2H, o-H,
3
3J = 7.7), 7.41 t (2H, m-H, J = 7.3), 7.24 t (1H, p-H,
3J = 7.3), 3.91 br.s (2H, CH2), 3.31 br.s (2H, CH2),
3
2.81 s (3H, NCH3), 2.77 t (2H, CH2, J = 6.2); in
3
CD3OD): 7.73 d (2H, o-H, J = 7.8), 7.38 t (2H, m-H,
3
3J = 7.6), 7.18 t (2H, p-H, J = 7.6), 3.88 br.s (2H,
3
1
CH2), 3.40–3.27 m (CH2)2, 2.85 t (2H, CH2, J = 6.6),
1046, 1008, 958, 913. H NMR spectrum, δ, ppm (J,
2.82 s (3H, NCH3). Found, %: C 67.93; H 7.01; N
18.45. m/z 229 [M]+. C13H15N3O. Calculated, %: C
68.11; H 6.50; N 18.32. M 229.26.
Hz): in D2O: 7.45–7.24 m (5H, C6H5), 4.15 d (1H, J =
14.2), 3.78 d (1H, J = 14.6), 3.71–3.58 m (1H), 3.38–
3.21 m (1H), 3.07–2.76 m (5H, CH2, NCH3); in
DMSO-d6–CCl4: 7.71 d (2H, o-H, J = 8.0), 7.42 t (2H,
m-H, J = 7.5), 7.23 t (1H, p-H, J = 7.5), 4.30 d.d (1H,
4-H, J = 2.6, 14.2), 3.95 d.d (1H, 4-H, J = 6.1, 14.2),
3.62–3.54 m (1H, CH2), 3.44–3.27 m (1H, CH2), 3.15–
2.96 m (1H, CH2), 2.92–2.78 d (4H, NMe, CH2). Mass
spectrum: m/z 229.12056 [M]+. Found, %: C 54.85; H
6.79; N 14.88; Cl 19.20. C26H33Cl3N6O2. Calculated,
%: C 54.98; H 5.86; N 14.80; Cl 18.73. M 229.12151
(for free base IIa).
The filtrate was combined with the washings and
evaporated, and the residue was recrystallized from
carbon tetrachloride to isolate 0.75 g of compound V.
5-Methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-
pyrazolo[4,3-c]pyridin-3-one sesquihydrochloride
(X). A mixture of 2.16 g (0.015 mol) of phenyl-
hydrazine hydrochloride and 3.1 g (0.015 mol) of
methyl 1-methyl-4-oxopiperidine-3-carboxylate hydro-
chloride (XIII) in 50 mL of anhydrous methanol was
heated at 50–60°C until it became homogeneous and
was then heated for 10 min under reflux. The solution
was filtered while hot, and the filtrate was left
overnight at room temperature. The precipitate (1.6 g)
was filtered off and washed on a filter with cold
5-Methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-
pyrazolo[4,3-c]pyridin-3-one hemihydrochloride (XI).
Compound XIII, 3.0 g (0.0144 mol) was dissolved in
40 mL of anhydrous methanol on heating, the solution
was cooled to 30°C and added to a solution of 1.56 g
(0.0144 mol) of phenylhydrazine, and the mixture was
stirred, allowing it to cool down to room temperature,
and was left to stand overnight (15 h). The light brown
2 The signal is obscured by the solvent.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

542
BUZYKIN et al.
Table 2. Crystallographic parameters of hydrochlorides X–XIII and conditions of X-ray diffraction experiments
Parameter
X
XI
XII
XIII
Color, habit
Space group
Formula
Colorless, prisms
P21/n
P21
P21/n
P21/n
C13H17N3O+·
C13H16N3O+·3Cl–
a 13.924(6),
b 13.770(4),
c 15.293(3),
β 115.50(3)°
2647(1)
C13H16N3O+·
C13H15N3O+·Cl–
a 6.037(3),
C13H17N3O·2Cl–
C8H14NO3+·Cl–
Unit cell parameters, Å
a 9.181(2),
b 6.984(1),
c 22.116(5),
β 101.31(2)°
1390.5(5)
a 11.121(7),
b 6.867(2),
c 13.523(4),
β 98.02(4)°
1022.6(8)
b 18.926(6),
c 11.020(5),
β 99.57(3)o
Volume, Å3
1241.6(9)
Z
4
2
4
4
Molecular weight
dcalc, g/cm3
567.93
1.425
3.435
1192
495.02
1.324
1.650
524
302.20
1.443
0.462
632
207.65
1.349
3.150
440
Absorption coefficient, mm–1
F(000)
Radiation source, λ, Å
CuKα,
CuKα,
MoKα,
λ 0.71073
CuKα,
λ 1.54184
λ 1.54184
λ 1.54184
Range of θ
3.60 ≤ θ ≤64.86
4.07 ≤ θ ≤71.40
2.61 ≤ θ ≤ 26.29
4.83 ≤ θ ≤ 64.83
Spherical segments
–15 ≤ h ≤ 0,
–16 ≤ k ≤ 0,
–16 ≤ l ≤ 16
3958
0 ≤ h ≤ 7,
–22 ≤ k ≤ 23,
–12 ≤ l ≤ 0
2161
–11 ≤ h ≤ 0,
–2 ≤ k ≤ 8,
–27 ≤ l ≤ 27
3226
–12 ≤ h ≤ 12,
–7 ≤ k ≤ 0,
–14 ≤ l ≤ 0
1449
Total number of reflections
Rint
0.0771
1702
0.0525
1427
0.0518
1034
0.0692
1282
Number of independent reflections with
I > 2σ(I)
Divergence factor for reflections
with I > 2σ(I)
R 0.0528,
Rw 0.1018
0.916
R 0.0251,
Rw 0.0588
0.982
R 0.0477,
Rw 0.0616
0.890
R 0.0360,
Rw 0.0949
0.997
Goodness of fit
Number of variables
349
260
185
129
Maximum and minimum residual electron
density peaks, e–/Å3
0.245,
0.058,
0.272,
0.354,
–0.236
–0.068
–0.352
–0.293
1
solution was diluted with an equal volume of diethyl
ether, the mixture was filtered, and the filtrate was left
to stand at room temperature. The precipitate was
filtered off and washed with methanol–diethyl ether.
Yield 2.1 g (58.8%), light yellow needles, mp 173–
175°C (decomp., PTP), 160–164°C (decomp.,
Boëtius). IR spectrum (KBr), ν, cm–1: 3114, 3039,
2959. 2934, 2904, 2852, 2807, 2653, 2590, 2569,
2467, 1663, 1624, 1589, 1557, 1489, 1456, 1431,
1416, 1350, 1326, 1243, 1202, 1177, 1120, 1089,
1061, 1042, 1021. H NMR spectrum (250 MHz,
D2O), δ, ppm: 7.59–7.41 m (4H, o-H, m-H), 7.40–7.28
m (1H, p-H), 4.01 br.s (1H), 3.49 br.s (1H), 2.99 s (3H,
NMe), 2.95–2.78 m (2H). Found, %: C 62.76; H 7.44;
N 16.94; Cl 7.10. C26H31ClN6O2. Calculated, %: C
63.08; H 6.31; N 16.98; Cl 7.16.
5-Methyl-2-phenyl-3,3a,4,5,6,7-hexahydro-2H-
pyrazolo[4,3-c]pyridin-3-one dihydrochloride (XII).
A solution of 0.5 g of hydrochloride X in 2 mL of
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

TAUTOMERISM OF AZA CYCLES: IV.
543
Lodochnikova, O.A., Islamov, L.R., Mobchan, A.I., and
Chmutova, G.A., J. Mol. Struct., 2002, vol. 610, nos. 1–
3, p. 175.
concentrated aqueous HCl was left to stand in an open
beaker at room temperature until water evaporated.
The residue was recrystallized from aqueous methanol
to isolate 0.35 g of XII as colorless prisms, mp 225–
227°C (decomp., PTP), 163–165°C (decomp. Boëtius).
IR spectrum (mineral oil), ν, cm–1: 3064, 3014, 2698,
2615, 2568, 2107, 1598, 1556, 1502, 1451, 1414,
1357, 1313, 1287, 1272, 1225, 1189, 1159, 1141, 1087,
4. Pfeffer, K.-G., Brandt, P., Buge, A., Hahn, H.-J., Heeger, G.,
and Reppel, L., Pharmazie, 1977, vol. 32, no. 11, p. 676.
5. Buzykin,
B.I.,
Abstracts
of
Papers,
III
Mezhdunarodnaya konferentsiya “Khimiya getero-
tsiklicheskikh soedinenii,” posvyashchennaya 95-letiyu
so dnya rozhdeniya professora A.N. Kosta (IIIrd Int.
Conf. “Chemistry of Heterocyclic Compounds”
Dedicated to the 95th Anniversary of Prof. A.N. Kost),
Moscow, 2010, p 12.
1
1046, 1021, 1008, 971, 953, 810, 771, 722, 697. H
NMR spectrum (DMSO-d6), δ, ppm (J, Hz): 11.55 s
(0.85H, N+H), 7.70 d (2H, o-H, J = 8.0), 7.35 t (2H,
m-H, J = 7.5), 7.06 t (1H, p-H, J = 7.5), 4.35 d (2H, J =
14.1), 4.00–3.91 m (1H), 3.61–3.50 m (1H), 3.34 s
(1H), 3.00–2.89 m (1H), 2.88 s (3H, NMe), 2.73–2.68
m (1H). Found, %: C 51.57; H 5.49; Cl 23.67; N
13.78. C13H17Cl2N3O. Calculated, %: C 51.63; H 5.63;
Cl 23.49; N 13.90.
6. Buzykin, B.I., Abstracts of Papers, Vserossiiskaya
nauchnaya konferentsiya “Uspekhi sinteza i komplekso-
obrazovaniya” (All-Russian Scientific Conf. “Advances
in Synthesis and Complex Formation”), Moscow, 2011,
p. 9.
7. Buzykin, B.I., Obzorn. Zh. Khim., 2013, vol. 3, no. 3,
p. 228.
Methyl 1-methyl-4-oxopiperidine-3-carboxylate
hydrochloride (XIII) was synthesized by cyclo-
condensation of dimethyl 3,3′-(methylimino)dipro-
panoate according to [36]. Recrystallization from
methanol–diethyl ether (10 : 1) gave colorless crystals
with mp 174–176°C (PTP), 170.5–172°C (Boëtius);
published data: mp 168°C [36], 172°C [37]). IR
spectrum (KBr), ν, cm–1: 3136, 3006, 2994, 2956,
2700–2170, 1677, 1617, 1554, 1485, 1474, 1417,
1401, 1378, 1365, 1328, 1296, 1257, 1227, 1183,
1145, 1132, 1102, 1061, 1028, 981, 944, 878, 821, 791,
767, 702. 1H NMR spectrum (DMSO-d6), δ, ppm: 12.2
br.s (1H, NH), 11.9 s (1H, OH), 3.80 s (3H, OMe),
3.75–3.65 m and 3.50–3.15 m (6H, CH2), 2.85 s (3H,
NMe). Mass spectrum, m/z (Irel, %): 172 (3), 171 (18)
[M]+, 172 (7), 156 (12) [M – Me]+, 138 (100) [M –
MeOH]+, 128 (6), 112 (29).
8. Bellamy, L.J., The Infra-red Spectra of Complex
Molecules, London: Methuen, 1958. Translated under
the title Infrakrasnye spektry slozhnykh molekul,
Moscow: Inostrannaya Literatura, 1963, p. 444.
9. Kurbangaleeva, A.R., Cand. Sci. (Chem.) Dissertation,
Kazan, 1999.
10. Raczyńska, E.D. and Kosińska, W., Chem. Rev., 2005,
vol. 105, no. 10, p. 3561.
11. Kabachnik, M.I., Zh. Vses. Khim. Ob–va., 1962, vol. 7,
no. 3, p. 263.
12. Sheinker, Yu.N., Izv. Sib. Otd. Akad. Nauk SSSR, Ser.
Khim. Nauk, 1980, no. 2, p. 37.
13. Englert, S.M.E. and McElvain, S.M., J. Am. Chem. Soc.,
1934, vol. 56, no. 3, p. 700.
14. Buzykin, B.I. and Nabiullin, V.N., Abstracts of Papers,
IV Vserossiiskii simpozium po organicheskoi khimii
“Upadok ili vozrozhdenie” (IVth All-Russian Symp. on
Organic Chemistry “Decadence or Renaissance”),
Moscow, 2003, p. 24.
ACKNOWLEDGMENTS
15. Alterburger, J.-M., Fossey, V., Illano, S., and Manette, G.,
Frehcn Patent no. 2940652, 2010; Chem. Abstr., 2010,
vol. 153, no. 145480.
16. Carpino, Ph.A., DaSilva, P.A., Lefker, B.A., and Ra-
gan, J.A., US Patent no. 6107306, 1997; Chem. Abstr.,
1997, vol. 127, no. 149410.
The authors thank R.Z. Musin for recording the
mass spectra. This study was performed under
financial support by the Russian Foundation for Basic
Research and Academy of Sciences of Tatarstan
Republic (project no. 12-03-97042r_povolzh’e_a).
17. Page, P., Laleu, B., Gaggini, F., and Orchard, M., EP
Patent no. 2361911, 2011; Chem. Abstr., 2011, vol. 155,
no. 352540.
REFERENCES
1. Buzykin, B.I., Mironova, E.V., Nabiullin, V.N.,
Azancheev, N.M., Avvakumova, L.V., Rizvanov, I.Kh.,
Gubaidullin, A.T., Litvinov, I.A., and Syakaev, V.V.,
Russ. J. Gen. Chem., 2008, vol. 78, no. 4, p. 634.
18. Vaitskyalёnene, R., Mitskyavichyus, V., and Mikul’-
skene, G., Chem. Heterocycl. Comp., 2004, no. 6,
p. 767.
2. Katritzky, A.K. and Maine, F.W., Tetrahedron, 1964,
vol. 20, no. 2, p. 299.
3. Kataeva, O.N., Gubaidullin, A.T., Litvinov, I.A.,
19. Hohenlohe-Oehringen, K., Saffer, D., Sporidi, G., and
Bretschneider, H., Monatsh. Chem., 1961, vol. 92, no. 2,
p. 313.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014

544
BUZYKIN et al.
20. Dickermann, S.C. and Lindwall, H.G., J. Org. Chem.,
28. Buzykin, B.I., Gubaidullin, A.T., Nabiullin, V.N., and
Litvinov, I.A., III Natsional’naya kristallokhimiches-
kaya konferentsiya (IIIrd National Conference on
Crystallochemistry), 2003, p. 92.
1949, vol. 14, no. 4, p. 530.
21. Aboul-Enein, S., Eur. J. Med. Chem., 1976, vol. 11,
no. 2, p. 133.
29. Altomare, A., Burla, M.C., Camalli, M., Cascarano, G.L.,
Giacovazzo, C., Guagliardi, A., Moliterni, A.G.G.,
Polidori, G., and Spagna, R., J. Appl. Crystallogr., 1999,
vol. 32, no. 1, p. 115.
30. Sheldrick, G.M., SHELX-97. Programs for Crystal
Structure Analysis (Release 97–2), Göttingen, Germany:
Univ.of Göttingen.
31. Straver, L.H. and Schierbeek, A.J., MOLEN. Structure
Determination System, vol. 1. Program Description,
Nonius B.V., 1994.
32. Farrugia, L.J., J. Appl. Crystallogr., 1999, vol. 32, no. 4,
p. 837.
22. Kharlamov, S.V., Balandina, A.A., Azancheev, N.M.,
Latypov, Sh.K., Nabiullin, V.N., and Buzykin, B.I.,
Abstracts of Papers, IV Vserossiiskaya konferentsiya
“Novye dostizheniya YaMR v strukturnykh issledo-
vaniyakh” (IVth All-Russian Conf. “New Advances of
NMR in Structural Studies”). Kazan’, 2005, p. 92.
23. Nabiullin V.N., Buzykin B.I., Gubaidullin A.G.,
Vserossiiskaya nauchnaya konferentsiya “Uspekhi
sinteza i kompleksoobrazovaniya” (All-Russian Sci-
entific Conf. “Advances in Synthesis and Complex
Formation”), Moscow, 2011, p. 188.
24. Nabiullin, V.N., Gubaidullin, A.T., Buzykin, B.I., and
Litvinov, I.A., Abstracts of Papers, III Natsional’naya
kristallokhimicheskaya konferentsiya (IIIrd National
Conference on Crystallochemistry), 2003, p. 94.
33. Spek, A.L., J. Appl. Crystallogr., 2003, vol. 36, no. 1,
p. 7.
34. Bruno, I.J., Cole, J.C., Edgington, P.R., Kessler, M.K.,
Macrae, C.F., McCabe, P., Pearson, J., and Taylor, R.,
Acta Crystallogr., Sect. B, 2002, vol. 58, no. 3, p. 389.
35. Macrae, C.F., Edgington, P.R., McCabe, P., Pidcock, E.,
Shields, G.P., Taylor, R., Towler, M., and van de Streek, J.,
J. Appl. Crystallogr., 2006, vol. 39, no. 3, p. 453.
36. Preobrazhenskii, N.A., Malikov, K.M., Maurit, M.E.,
Vorob’ev, M.A., and Vlasov, A.S., Zh. Obshch. Khim.,
1957, vol. 27, no. 11, p. 3162.
25. Buzykin, B.I., Nabiullin, V.N., Gubaidullin, A.T., and
Kharlamov, S.V., Russ. J. Gen. Chem., 2013, vol. 83,
no. 11, p. 2084.
26. Allen, F.H., Kennard, O., Watson, D.G., Brammer, L.,
Orpen, A.G., and Taylor, R., J. Chem. Soc., Perkin
Trans. 2, 1987, no. 12, p. S1.
27. Litvinov, I.A., Struchkov, Yu.T., Bystrykh, N.N., Kita-
ev, Yu.P., and Buzykin, B.I., Chem. Heterocycl. Comp.,
1982, no. 7, p. 749.
37. Dobrovsky, A., Monatsh. Chem., 1952, vol. 83, no. 2,
p. 443.
RUSSIAN JOURNAL OF GENERAL CHEMISTRY Vol. 84 No. 3 2014