Synthesis of pyrrol-2-yl- and pyrazol-4-ylmethylidene derivatives of betulin and allobetulin

Article abstract of DOI:10.1134/S1070428015050231

Aldol-crotonic condensation of allobetulone and betulonic aldehyde with N-substituted pyrrole-2- and pyrazole-4-carbaldehydes afforded a series of new α,β-unsaturated ketones of lupane series. Their reduction provided 2-ylidene derivatives of allobetulin

Full text of DOI:10.1134/S1070428015050231

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2015, Vol. 51, No. 5, pp. 715–726. © Pleiades Publishing, Ltd., 2015.
Original Russian Text © N.L. Babak, A.N. Semenenko, I.M. Gella, V.I. Musatov, S.V. Shishkina, N.B. Novikova, D.S. Sofronov, D.A. Morina, V.V. Lipson,
2015, published in Zhurnal Organicheskoi Khimii, 2015, Vol. 51, No. 5, pp. 731–742.
Synthesis of Pyrrol-2-yl- and Pyrazol-4-ylmethylidene Derivatives
of Betulin and Allobetulin
N. L. Babaka, A. N. Semenenkoa, I. M. Gellaa,c, V. I. Musatova, S. V. Shishkinaa,
N. B. Novikovaa, D. S. Sofronova, D. A. Morinac, and V. V. Lipsona,b,c
a Institute of Single Crystals, National Academy of Sciences of Ukraine, pr. Lenina 60, Kharkiv, 61001 Ukraine
e-mail: lipson@ukr.net
b Danilevskii Institute of Problems of Endocrine Pathology, National Academy of Medical Sciences of Ukraine, Kharkiv, Ukraine
c Karazin Kharkiv National University, Kharkiv, Ukraine
Received March 6, 2015
Abstract—Aldol-crotonic condensation of allobetulone and betulonic aldehyde with N-substituted pyrrole-2-
and pyrazole-4-carbaldehydes afforded a series of new α,β-unsaturated ketones of lupane series. Their
reduction provided 2-ylidene derivatives of allobetulin and betulin, potential chiral components of liquid crystal
materials. Structures of 1-phenyl-3-(4-phenoxyphenyl)-1H-pyrazole-4-carbaldehyde, (E)-2-{[3-(4-
methoxyphenyl)-1-phenyl-1H-pyrazol-4-yl]methylidene}allobetulone, (E)-2-{[3-(4-bromophenyl)-1-phenyl-
1H-pyrazol-4-yl]methylidene}-3-oxolup-20(29)-ene-28-carbaldehyde, (E)-2-{[3-(4-bromo-phenyl)-1-phenyl-
1H-pyrazol-4-yl]methylidene}allobetulin, and (E)-2-{[3-(4-bromophe-nyl)-1-phenyl-1H-pyrazol-4-yl]-
methylidene}lup-20(29)-ene-3,28-diol were established by X-ray diffraction (XRD) study .
DOI: 10.1134/S1070428015050231
Modification of naturally occurring chiral compounds
with a polycyclic carbon scaffold, like triterpenoids and
steroids, by introducing heterocyclic substituents in their
composition is one of procedures generating structural
diversity of active pharmaceutical ingredients. This me-
thod is widely accepted in medicinal chemistry [1, 2].
significantly weaker compared with commercial
products from the group of tetraaryl derivatives of 1,3-
dioxolane-4,5-dimethanol [7, 8], dianhydro-D-glucitols
[9, 10], and chiral axial derivatives of binaphthyl [11,
12].
We obtained 2-(1-arylpyrrol-2-yl)- and (1-phenyl-
3-arylpyrazol-4-yl)methylidene derivatives of
triterpenoids of lupane series and carried out the
comparable estimation of the twisting power (β) of the
obtained substances in the nematic solvent 5CB (4'-
pentyl-1,1'-biphenyl-4-carbоnitrile), one of the basic
parameters, which determines the possibility of their
further practical use.
We applied it to solve a problem in material
science, for the preparation of opically active substan-
ces suitable for designing chiral-nematic (cholesteric)
liquid crystal compositions, selectively reflecting light
in the visible spectral region. These materials are used
in bistable displays of various low-energy devices for
demonstration of information acting by reflection
effect, like electronic paper, advertisement screens [3].
Among the chiral dopants to the nematic liquid crystal
compositions arylsubstituted terpenoids are known
(arylmethylidenementhones) [4], and also 16-aryl- and
16-hetarylmethylidene derivatives of 17-oxosteroids of
androstane and estrane series [5, 6]. However by their
specific physicochemical characteristics, mainly by the
ability to induce in the nematic mesophase a helical
supramolecular structure ensuring the selective light
reflection in the visible range of wavelengths, they are
The selection of N-aryl-substituted heterocyclic
aldehydes of pyrrole and pyrazole series applied as
carbonyl components in the crotonic condensation with
the methylene-active compounds of the lupane series is
due to the presence in their structure of a developed π-
electronic system, and to the location of the axes of the
aryl substituents in the heterocycle at an angle to each
other, in contrast, e.g., to amylbiphenyl fragment, the
most widely spread promesogenic group in the
structure of chiral dopants.
715

BABAK et al.
716
Scheme 1.
tions of the СN and С=О groups were observed at 2224
1
and 1643 cm–1 respectively. Н NMR spectrum of this
O
POCl3
DMF
HOAc
compound contained the signals from all proton
groups. The most characteristic proton signal was the
singlet of the formyl proton at δ 9.54 ppm. The
physicochemical characteristics of aldehydes 8a–8е
correspond to published data [15]. The structure of
compound 8е is confirmed by the data of XRD
analysis (Fig. 1). The formyl and phenyl substituents
in the molecule 8е are practically coplanar with the
plane of the pyrazole ring [torsion angles С1С2С16О2 –
0.5(5) deg, С1N2C17C22 3.6(5) deg]. Aromatic ring
С4֥С9 at the atom С3 is disordered by two positions А
and В with equal probability of population due to the
rotation around the С3–С4 bond and is turned with
respect to the heterocycle plane in both conformers
[torsion angle С5С4С3С2 33.6(6)° in conformer А and –
21.3(6)° in conformer В]. Presumably the lack of the
rings coplanarity is caused by the steric repulsion
between the vicinal substituents [shortened intramo-
lecular contacts С5֥С16 3.36 (А), 3.27 Å (В) (sum of
the van der Waals radii [16] 3.42 Å); Н5֥С16 2.84 (А),
2.70 Å (В) (2.87 Å); Н5֥Н16 2.21 (А), 2.01 Å (В)
(2.34 Å); Н16֥С5 2.80 (А), 2.67 Å (В) (2.87 Å)].
O
R'
+
N
N
O
NH2
O
R'
3a, 3b
R'
4a, 4b
1a, 1b
2
R' = 4-(4'-CNC6H4)C6H4 (а), 2,6-Me2C6H3 (b).
Scheme 2.
R
H
N
NH2
+
O
5a_5e
6
R
N
POCl3
DMF
N
HOAc
EtOH
H
N
N
O
R
7a_7e
8a_8e
R = Br (a), CH3 (b), OCH3 (c), Ph (d), OPh (e).
Refluxing of equimolar quantities of allobetulone 9
with aldehydes 4a, 4b and 8a–8e in alcoholic medium
in the presence of KОН for 6–8 h resulted in the
formation of α,β-unsaturated ketones 10a, 10b and
11a–11e in 80–85% yields [17]. Under similar
conditions we synthesized 2-ylidene derivatives of
betulonic aldehyde 13a–13e (Scheme 3).
Pyrrole-2-carbaldehydes 4а and 4b were prepared
according to Scheme 1 [13, 14], pyrazole-4-carbalde-
hydes 8a–8e were obtained by formylation of
hydrazones 7a–7e in the conditions of Vilsmeier-Haak
reaction (Scheme 2) [15].
The composition and structure of compounds 3а
and 4а were confirmed by the data of elemental analy-
sis, IR and 1Н NMR spectra. In the IR spectrum of alde-
hyde 4а the absorption bands of the stretching vibra-
The structure and the composition of α,β-un-
saturated ketones 10a, 10b, 11a–11e and 13a–13e were
confirmed by the data of IR, 1Н NMR spectra, and also
by XRD analysis of crystals of compounds 11с, 13а.
The IR spectra of the unsaturated ketones originating
from allobetulone 10а, 10b and 11a–11e contain in the
region 2969–2859 cm–1 characteristic absorption bands
of the methyl and methylene groups from the lupane
scaffold, and at 1140 cm–1 the bands of the ether
moiety of the tetrahydrofuran ring are observed. The
shift of the stretching vibrations of the С=О group
from 1701 cm–1 to the region of smaller wave numbers
(1676–1670 cm–1) transition from allobetulone 9 to
unsaturated ketones 10a, 10b and 11a–11e is typical of
compounds with the ylidene fragment [18].
Fig. 1. Molecular structure of 3-(4-phenoxyphenyl)-1-phe-
nyl-pyrazole-4-carbaldehyde 8е according to XRD data.
Ellipsoids of thermal oscillations of atoms are shown in
30% probability.
In the IR spectra of α,β-unsaturated ketones 13а–
13е the absorption bands of the stretching vibrations of
the carbonyl groups appeared at 1673 (keto group) and
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SYNTHESIS OF PYRROL-2-YL- AND PYRAZOL-4-YLMETHYLIDENE DERIVATIVES
717
Scheme 3.
O
O
N
R'
KOH
N
O
+
CH3OC2H4OH
R'
O
O
9
4a, 4b
10a, 10b
N
N
O
O
N
N
KOH
R
+
CH3OC2H4OH
R
O
O
O
9
8a_8e
11a_11e
N
N
O
N
N
KOH
O
+
CH3OC2H4OH
R
R
O
O
O
12
8a_8e
13a_13e
4, 10, R' = 4-(4'-CNC6H4)C6H4 (а), 2,6-Me2C6H3 (b); 8, 11, 13, R = Br (a), CH3 (b), OCH3 (c), Ph (d), OPh (e).
1726–1717 cm–1 (formyl group). In this case the maxi-
mum of the keto group absorption band is also shifted
under the influence of the ylidene fragment to the region
of smaller wave numbers as compared to the value
1702 cm–1 in the initial compound 12; the position of
ν(С=О) of the formyl group remained unchanged.
The 1Н NMR spectra of 2-ylidene derivatives of allo-
betulone 10а, 10b and 11a–11e contain the multiplets
of the protons of aromatic rings, the signals of the pro-tons
of pyrrole (6.57–6.84) or pyrazole (8.03–8.05 ppm) rings.
The singlet of vinyl proton is observed at 7.28–7.71 ppm
and is often overlapped with the signals of aryl substi-
tuents. The tetrahydrofuran ring appears as doublets of
protons of СН2 group (АВ system), δ 3.45–3.78 ppm, and
a singlet of СН group at 3.53–3.57 ppm. The multiplets
of methine and methylene protons of the lupane scaffold
are located at 1.01–1.74 ppm, and the singlets of the
seven methyl groups, in the range 0.78–1.17 ppm.
1Н NMR spectra of α,β-unsaturated ketones derived
from betulonic aldehyde 13a–13e differ from the
spectra of compounds 10а, 10b and 11a–11e by the
signal of the formyl proton at 9.65 ppm, the singlet of
the methyl group of the isopropylidene moiety (δ 1.71–
1.73), and by the doublet of the vinyl protons of СН2
group (4.70–4.72 ppm).
The unambiguous proof of the steric structure of
α,β-unsaturated ketones 11а–11е and 13а–13е was
obtained from the XRD analysis of single crystals of
compounds 11с and 13а (Fig. 2). The ring А
[С1С2С3С4С20(21)С21(22)] in molecules of compounds 11с
and 13а is present in the conformation distorted sofa
(puckering parameters and the deviations of atoms С3,
С4 from the least-squares plane of the other atoms of
the ring are listed in Table 1). A conjugation exists
between the pyrasole ring and the fragment С31С2С1О1
leading to the flattening of the ylidene fragment of the
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 5 2015

BABAK et al.
718
Fig. 2. Molecular structure of (E)-2-{[3-(4-methoxyphe-
nyl)-1-phenyl-1H-pyrazol-4-yl]methylidene}allobetulone
11с (а) and (E)-2-{[3-(4-bromophenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}-3-oxolup-20(29)-ene-28-carbalde-
hyde 13а (b) according to XRD data. Ellipsoids of thermal
oscillations of atoms are shown in 30% probability.
Fig. 3. Molecular structure of (E)-2-{[3-(4-methoxyphe-
nyl)-1-phenyl-1H-pyrazol-4-yl]methylidene}allobetulin
15с (a) and (E)-2-{[3-(4-bromophenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}lup-20(29)-ene-3,28-diol 16а (b) ac-
cording to XRD data. Ellipsoids of thermal oscillations of
atoms are shown in 30% probability.
molecule (torsion angles О1С1С2С31, С3С2С31С32, and
С2С31С32С34, Table 1), despite the considerable steric
repulsion between the atoms of the pyrazole ring and
ring А. Phenyl and 4-methoxyphenyl substituents are
turned with respect to the plane of the pyrazole ring
evidently due to the steric strain. The corresponding shor-
tened intramolecular contacts are reported in Table 1.
betulin derivatives 16a–16e the signal of the formyl pro-
ton is missing, and the singlet of the vinyl proton shifts to
the region 6.48–6.59 ppm. The protons of the С28Н2 group
appear as an АВ system, δ 3.29–3.79 ppm, J ~11 Hz.
2-Ylidene derivatives of allobetulin 14b and 15a–
15e and of betulin 16a–16e were obtained by reduction
the corresponding unsaturated ketones 10b, 11a–11e
and 13a–13e with NaBH4 in a mixture MеОН–СН2Cl2,
1 : 1 [19] (Scheme 4).
The unambiguous proof of the steric structure of
allyl alcohols 15а–15е and 16а–16е was obtained from
the XRD analysis of single crystals of compounds 15с
and 16а (Fig. 3). The reduction of the exocyclic С=О
double bond results in a considerable change in the
conformation of ring А (as compared with compounds
11с and 13а) that takes a chair form (folding
parameters and the deviations of atoms С1 and С4 from
the least-squares plane of the other atoms of the ring
are compiled in Table 2). Presumably the shortening of
the conjugation chain results in the distortion of the
coplanarity of the pyrazole ring and the exocyclic
IR spectra of compounds14b, 15a–15e and 16a–16e
lack the absorption band of the carbonyl group, and a bro-
adened band is observed corresponding to the vibrations
of associated OH groups in the region 3360–3467 cm–1.
1Н NMR spectra of allobetulin derivatives 14b and
15a–15e are different from the above described spectra
of α,β-unsaturated ketones 10b and 11a–11e by the
presence of a singlet from the proton in the position 3 of
the lupane scaffold, δ 3.82–3.88 ppm. In the spectra of
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SYNTHESIS OF PYRROL-2-YL- AND PYRAZOL-4-YLMETHYLIDENE DERIVATIVES
719
Table 2. Some geometric parameters of molecules 15с and
16а
Table 1. Some geometric parameters of molecules 11с and
13а
Parameter
11с
13а
Parameter
15с
16а
Folding parameters
Folding parameters
S
Θ
Ψ
0.76
46.6
11.8
0.75
49.5
6.9
S
Θ
Ψ
1.12
2.0
24.5
1.12
4.5
1.2
Deviation of atoms from the plane of ring А, Å
Deviation of atoms from the plane of ring А, Å
С3
–0.17
–0.82
Torsion angles, deg
–10.1(7)
–0.14
–0.82
С1
С4
–0.64
0.68
–0.67
0.64
С4
Torsion angles, deg
0.2(6)
O1C1C2C31
–10.4(5)
–1.2(5)
10.9(6)
24.6(5)
–49.8(5)
O1C1C2C31
7.7(5)
–1.9(7)
–34.3(5)
21.6(7)
45.5(7)
С3С2С31С32
С2С31С32С34
С34N2C35C40
C32C33C41C42
3.1(7)
С3С2С31С32
С2С31С32С34
С34N2C35C40
C32C33C41C42
3.2(8)
–0.7(8)
22.5(7)
–34.3(9)
–40.3(7)
Shortened contacts, Å
32.6(7)
С34֥С3
Н34֥С3
Н3а֥С34
Н34֥Н3а
Н40֥С34
Н34···С40
Н36֥N1
C42…C31
H31֥C42
H31֥H42
H46֥N1
3.15
3.14
2.66
2.58
2.06
2.70
2.85
2.58
3.35
2.74
–
–37.8(8)
Shortened contacts, Å
2.65
2.67
2.12
2.70
2.84
2.55
3.31
2.67
2.21
2.61
С34֥С3
Н3а֥С34
Н3а֥Н34
Н40֥С34
Н34֥С40
Н36֥N1
Н34֥Н40
C42֥C31
H31֥C42
H31֥H42
H46֥N1
Н42֥С31
Н3а֥С32
Н3а֥С33
С3֥С41
С3֥С46
Н3а֥С41
3.39
2.67
2.23
2.83
–
–
–
–
2.68
2.81
2.63
2.31
–
2.54
–
3.16
2.73
–
–
–
2.63
2.73
–
–
double bond С2–С31 (Table 2) because of the steric
repulsion between the atoms of the pyrazole and
cyclohexane rings. Same as in compounds 11с and
13а, in allyl alcohols 15с and 16а the phenyl and 4-
methoxyphenyl substituents considerably deviate from
the pyrazole ring plane evidently due to the steric
strain. The corresponding shortened intramolecular
contacts are shown in Table 2. In the molecule of 4-
bromophenyl derivative 16а the substituent at
exocyclic double bond is turned to the opposite side as
compared with the analogous substituent in molecule
13а (torsion angle С2С31С32С34, Table 2). This
conformation is additionally stabilized by the
formation of an intramolecular СН֥π hydrogen bond
С3Н3а֥С41 (Н֥С 2.50 Å, angle СН֥С 137°).
–
2.73
2.75
3.28
3.34
2.50
–
–
–
–
the nematic solvent 5CB are collected in Table 3. The
largest |β| was observed in the series of 2-ylidene
derivatives of allobetulone 10а and 11а–11е, excuding
compound 10b possessing the shortest conjugation
chain. The |β| values for compounds 10а and 11а–11е
are significantly larger than for the substance we have
obtained lately, (Е)-2-[(4'-pentyl-1,1'-biphenyl-4-yl)me-
thylide-ne]allobetulone (|β| 10.75 ± 0.53 mmol–1 µm–1 d–1)
[19]. Therefore the increase in the value of twisting
The data on the twisting power |β| of compounds
10a, 10b, 11a–11e, 13a–13e, 15a–15e and 16a–16e in
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 5 2015

BABAK et al.
720
Scheme 4.
29
30
19
30
19
29
O
O
N
N
R'
R'
28
26
25
24
28
26
25
24
NaBH4
1
1
MeOH, CH2Cl2
2
3
2
3
27
27
HO
O
N
23
23
10b
14b
N
N
N
O
O
NaBH4
R
R
MeOH, CH2Cl2
HO
O
11a_11e
15a_15e
29
20
29
20
30
26
30
N
N
N
N
O
OH
25
25
26
NaBH4
1
28
1
R
R
28
2
3
2
3
MeOH, CH2Cl2
27
27
HO
O
23
24
23
24
13a_13e
16a_16e
10, 14, R' = 2,6-Me2C6H3 (b); 11, 13, 15, 16, R = Br (a), CH3 (b), OCH3 (c), Ph (d), OPh (e).
power may be related to the growing length of the π-
system of the promesogenic fragment. The reduction
products 15а–15е with respect to the capability to
induce the helical supramolecular structure in the
nematic solvent 5CB are worse than α,β-unsaturated
ketones 11а–11е and the previously obtained (Е)-2-
[(4'-pentyl-1,1'-biphenyl-4-yl)methylidene]allobetulin
(|β| 144.46 ± 3.13 mmol–1 µm–1 d–1) [19]. This fact
originates apparently from the distortion of the
conjugation between the promesogenic 2-ylidene frag-
ment and the carbonyl group and the change in the
twist-boat conformation of ring А in compounds 11а–
11е into the chair conformation in derivatives of allo-
betulin 15а–15е. The latter was confirmed by the XRD
results. The differences in the twisting power of hyd-
roxyl derivatives 15а–15е and (Е)-2-[(4'-pentyl-1,1'-
biphenyl-4-yl)methylidene]allobetulin is caused by the
molecular geometry of compounds 15a–15e unsuitable
for an efficient induction of cholesteric mesophase.
In the series of derivatives of betulonic aldehyde
13a–13e and betulin 16a–16e the changes in the con-
jugation chain as well as the reduction of the carbonyl
groups weakly affect the twisting power. Thus for the effi-
cient induction of helicoid supramolecular structure the
essential importance is governed not only by the type of
the promesogenic fragment but also by the steric structure
of the chiral supramolecular scaffold as a whole.
EXPERIMENTAL
IR spectra were registered on a spectrometer
Perkin-Elmer Spectrum One FTIR from pellets with
1
KBr. Н NMR spectra were registered on a spec-
trometer Varian Mercury VX 200 (200 MHz) in
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SYNTHESIS OF PYRROL-2-YL- AND PYRAZOL-4-YLMETHYLIDENE DERIVATIVES
721
Table 3. Twisting power |β|, µm–1 mol d–1/µm–1 d–1, of compounds 10a, 10b, 11a–11e, 13a-13e, 15a–15e and 16a–16e in
solvent 5CB
O
O
R
R
O
O
R
O
R
OH
R
HO
HO
15a–15e
13a–13e
10a, 10b, 11a–11e
16a–16e
108.86 ± 4.31/
36.40 ± 1.44
51.87 ± 1.64/
17.17 ± 0.64
80.32 ± 1.40/
26.93 ± 0.44
84.32 ± 3.40/
28.06 ± 1.0
N
N
Br
129.94 ± 2.81/
47.53 ± 8.34
52.74 ± 2.11/
19.35 ± 1.28
70.51 ± 1.67/
25.83 ± 0.61
83.14 ± 2.49/
30,39 ± 0.41
N
N
145.02 ± 1.28/
51.97 ± 0.27
63.83 ± 0.30/
22.72 ± 0.11
58.34 ± 1.32/
20.91 ± 0.47
62.96 ± 1.51/
22.42 ± 0.54
N
N
O
158.61 ± 8.70/
53.28 ± 2.92
61.67 ± 1.33/
20.66 ± 0.72
77.43 ± 3.1/
26.08 ± 1.4
77.77 ± 0.11/
26.12 ± 0.04
N
N
N
N
106.41 ± 2.42/
34.61 ± 1.59
49.19 ± 2.02/
16.40 ± 0.82
58.87 ± 1.65/
19.41 ± 0.51
70.24 ± 0.81/
22.99 ± 0.04
O
N
89.67; 79.58/32.4;
28.71
N
10а
N
6.75/2.71
10b
CDCl3, internal reference TMS. Elemental analysis
was carried out on an elemental analyzer EA 3000
Eurovektor (CHNS-analysis). Melting points were
measured on a Koeffler heating block. The reaction
progress was monitored and the purity of compounds
obtained was checked by TLC on Alugram® Xtra SIL
G/UV254 plates, eluent hexane–ethyl acetate, 10 : 1.
Allobetulone 9 and betulonic aldehyde 12 were
obtained by procedures [20, 21].
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BABAK et al.
722
Table 4. Crystallographic data and parameters of XRD experiment for compounds 8e, 11c, 13a, 15c and 16a
Parameter
8e
11c
13a
7.7634(3)
22.4137(9)
22.550(1)
90.0
15c
16a
a, Å
21.932(3)
5.2213(6)
16.122(2)
90.0
6.9022(9)
12.543(2)
44.849(4)
90.0
6.5971(7)
11.572(1)
51.631(4)
90.0
11.0944(5)
12.2101(5)
16.0364(6)
90.0
b, Å
c, Å
α, deg
β, deg
110.91(2)
90.0
90.0
90.0
91.00(3)
γ, deg
V, Å3
90.0
90.0
90.0
90.0
90.0
1724.5(4)
3882.7(8)
3923.8(3)
3941.5(6)
2171.9(1)
F(000)
712
Monoclinic
P21/с
4
1520
Rhombic
P212121
4
1584
Rhombic
P212121
4
1528
Rhombic
P212121
4
824
Monoclinic
P21
Crystal system
Space group
Z
2
T, K
293
293
293
293
293
μ, mm–1
dcalc, g/cm3
0.085
1.311
50
0.074
1.199
50
1.087
1.266
60
0.073
1.185
50
0.985
1.183
60
2Θmax, deg
Reflections collected
10908
2968
15535
6764
22267
11144
0.047
5556
27262
6832
22745
11940
0.044
6764
Independent reflections
Rint
0.073
1374
0.113
3299
0.102
5183
Reflections with F > 4σ(F)
Parameters
272
477
470
482
499
R1
0.056
0.140
0.868
1044960
0.075
0.155
0.905
1044961
0.080
0.111
1.005
1044962
0.095
0.156
1.042
1044963
0.066
0.145
0.938
1044964
wR2
S
CCDC no.
4'-(1H-Pyrrol-1-yl)-1,1'-biphenyl-4-carbоnitrile
(3а). Yield 83%, mp 190–192°C. IR spectrum, ν, cm–1:
Нformyl). Found, %: С 79.35; Н 4.40; N 10.24.
С18Н12N2О. Calculated, %: С 79.40; Н 4.44; N 10.29.
1
2218 (C≡N). H NMR spectrum, δ, ppm: 6.24–6.31 m
2 , 5
(2H, H3p,y4rrol), 7.41–7.48 m (2H, H
), 7.70 d (2H,
1-(2,6-Dimethylphenyl)-1H-pyrrole-2-carbalde-
hyde (4b). Yield 90%, mp 47–49°C. IR spectrum, ν,
p y rrol
H2',6', J 8.6 Hz), 7.83 d (2H, H3',5', J 8.8 Hz), 7.87–7.93 m
(4H, C6H4CN). Found, %: С 83.55; Н 4.91; N 11.44.
С13Н12N2. Calculated, %: С 83.58; Н 4.95; N 11.47.
1
cm–1: 1668 (C=O). H NMR spectrum, δ, ppm: 1.91 s
(6H, 2CH3), 6.58 s (1H, H4pyrrole), 6.85 s (1H, H3pyrrole),
7.04–7.32 m (3H, H3',4',5'), 7.61 s (1H, H5pyrrole), 9.66 s
(1H, Нformyl). Found, %: С 78.35; Н 5.53; N 7.01.
С13Н13NО. Calculated, %: С 78.36; Н 5.58; N 7.03.
4'-(4-Formyl-1H-pyrrol-1-yl)-1,1'-biphenyl-4-car-
bоnitrile (4а). Yield 86%, mp 168–170°C. IR spec-
trum, ν, cm–1: 2224 (C≡N), 1643 (C=O). 1H NMR spec-
trum, δ, ppm: 6.47 d.d (1H, H4pyrrole, J 3.90, 2.70 Hz),
7.25 d.d (1H, H3pyrrole, J 3.90, 1.60 Hz), 7.46 s (1H,
4'-{2-[(E)-(3-Oxoallobetulan-2-ylidene)-methyl]-
1H-pyrrol-2-yl}-1,1'-biphenyl-4-carbоnitrile (10а). A
mixture of 1 g (2.3 mmol) of allobetulone 9 and 0.68 g
(2.5 mmol) of heterocyclic aldehyde 4a in 15–20 mL
H5pyrrole), 7.54 d (2H, H2',6', J 8.5 Hz), 7.84 d (2H, H3',5'
,
J 8.5 Hz), 7.87–7.97 m (4H, C6H4CN), 9.54 s (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 5 2015

SYNTHESIS OF PYRROL-2-YL- AND PYRAZOL-4-YLMETHYLIDENE DERIVATIVES
723
of ethylene glycol monomethyl ether was refluxed for
6–8 h in the presence of a catalytic amount of KOH.
On cooling the separated precipitate was filtered off
and washed with alcohol. Yield 1.31 g (84%). White
amor-phous powder, mp 287–289°C. IR spectrum, ν,
cm–1: 2924–2861 (CH3, CH2), 2218 (C≡N), 1672
(21H, 7CH3), 2.12 d (1Н, H1a, J 15.9 Hz), 2.40 s (3H,
4'-CH3), 2.97 d (1H, H1e, J 16.2 Hz), 3.46 d (1H, H28A
,
J 7.7 Hz), 3.56 s (1Н, H19), 3.79 d (1H, H28B, J 7.7 Hz),
7.27 d (2H, H3,5', J 6.9 Hz), 7.32–7.68 m (6H, C6H5 +
H
vinyl), 7.76 d (2H, H2',6', J 7.9 Hz), 8.03 s (1H,
Нpyrazole). Found, %: С 82.40; Н 8.31; N 4.05.
С47Н60N2О2. Calculated, %: С 82.41; Н 8.33; N 4.09.
1
(C=O), 1142 (C–O–C). H NMR spectrum, δ, ppm:
0.81 s, 0.85 s, 0.93 s, 0.96 s, 1.02 s, 1.11 s (21H,
7CH3), 2.15 d (1Н, H1a, J 18.3 Hz), 3.06 d (1H, H1e, J
16.3 Hz), 3.45 d (1H, H28A, J 7.9 Hz), 3.56 s (1Н, H19),
3.78 d (1H, H28B, J 7.7 Hz), 6.38–6.47 m (1H, H4pyrrole),
6.66 d (1H, H3pyrrole, J 3.0 Hz), 7.04 d.d (1H, H5pyrrole, J
3.60, 1.30 Hz), 7.35 d (2H, H2',6', J 8.4 Hz), 7.60–7.75
m (4H, C6H4CN), 7.90 d (2H, H3',5', J 8.3 Hz). Found,
%: С 82.91; Н 8.38; N 4.00. С48Н60N2О2. Calculated,
%: С 82.95; Н 8.41; N 4.03.
(E)-2-{[3-(4-Methoxyphenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}allobetulone (11с). Yield 1.34 g
(85%). White amorphous powder, mp 250–252°C. The
crystals were grown from a mixture methylene chlori-
de–ethanol, 1 : 3. IR spectrum, ν, cm–1: 2970–2864 (CH3,
1
CH2), 1670 (C=O), 1247 (O–CH3), 1140 (C–O–C). H
NMR spectrum, δ, ppm: 0.83 s, 0.88 s, 0.95 s, 0.98 s,
1.04 s, 1.10 s, 1.17 s (21H, 7CH3), 2.12 d (1Н, H1a, J
15.5 Hz), 2.97 d (1H, H1e, J 16.2 Hz), 3.47 d (1H, H28A
,
Compounds 10b, 11a–11e and 13a–13e were
obtained similarly.
J 7.7 Hz), 3.57 s (1Н, H19), 3.78 d (1H, H28B, J 7.7 Hz),
3.85 s (3H, CH3OC6H4), 7.00 d (2H, H3',5', J 8.8 Hz),
7.29–7.67 m (6H, C6H5 + Hvinyl), 7.76 d (2H, H2',6', J
8.2 Hz), 8.03 s (1H, Нpyrazole). Found, %: С 80.49; Н
8.61; N 4.00. С47Н60N2О3. Calculated, %: С 80.53; Н
8.63; N 4.00.
(E)-2-{[1-(2,6-Dimethylphenyl)-1H-pyrrol-2-yl]-
methylidene}allobetulone (10b). Yield 1.12 g (80%).
White amorphous powder, mp 206–208°C. IR
spectrum, ν, cm–1: 2947–2863 (CH3, CH2), 1670
1
(C=O), 1140 (C–O–C). H NMR spectrum, δ, ppm:
(E)-2-{[3-(1,1'-Biphenyl-4-yl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}allobetulone (11d). Yield 1.35 g
(80%). White amorphous powder, mp 295–297°C. IR
spectrum, ν, cm–1: 2949–2866 (CH3, CH2), 1671 (C=O),
0.78 s, 0.86 s, 0.91 s, 0.93 s, 1.01 s, 1.08 s, 1.15 s
(21H, 7CH3), 2.02 s [6Н, 2,6-(CH3)2C6H3], 2.14 d (1Н,
H1a, J 18.6 Hz), 2.99 d (1H, H1e, J 17.6 Hz), 3.44 d
(1H, H28A, J 6.8 Hz), 3.53 s (1Н, H19), 3.77 d (1H,
1141 (C–O–C). H NMR spectrum, δ, ppm: 0.81 s,
1
3 , 4
H28B, J 6.5 Hz), 6.57 d (2H, CH
, J 15.4 Hz), 6.84
0.88 s, 0.94 s, 0.96 s, 1.02 s, 1.11 s, 1.17 s (21H,
7CH3), 2.12 d (1Н, H1a, J 16.2 Hz), 2.98 d (1H, H1e, J
16.2 Hz), 3.45 d (1H, H28A, J 7.7 Hz), 3.55 s (1Н, H19),
3.78 d (1H, H28B, J 7.6 Hz), 7.28–7.85 m (15H, C12H9 +
C6H5 + Hvinyl), 8.05 s (1H, Нpyrazole). Found, %: С 83.55;
Н 8.31; N 3.73. С52Н62N2О2. Calculated, %: С 83.60;
Н 8.37; N 3.75.
p y rrol
s (1H, CH4pyrrole), 6.96–7.35 m (3H, H3,4,5, C6H3), 7.50
s (1H, Нvinyl). Found, %: С 83.01; Н 9.52; N 2.24.
С43Н59NО2. Calculated, %: С 83.04; Н 9.56; N 2.25.
(E)-2-{[3-(4-Bromophenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}allobetulone (11а). Yield 1.37 g
(81%). White amorphous powder, mp 275–277°C. IR
spectrum, ν, cm–1: 2982–2863 (CH3, CH2), 1670 (C=O),
1140 (C–O–C). 1H NMR spectrum, δ, ppm: 0.83 s, 0.87
s, 0.94 s, 0.98 s, 1.03 s, 1.11 s, 1.17 s (21H, 7CH3), 2.14 d
(1Н, H1a, J 16.1 Hz), 2.96 d (1H, H1e, J 14.9 Hz), 3.46 d
(E)-2-{[1-Phenyl-3-(4-phenoxyphenyl)-1H-pyra-
zol-4-yl]methylidene}allobetulone (11e). Yield 1.41 g
(82%). White amorphous powder, mp 265–267°C. IR
spectrum, ν, cm–1: 2924–2859 (CH3, CH2), 1676 (C=O),
1229 (O–C6H5), 1140 (C–O–C). 1H NMR spectrum, δ,
ppm: 0.81 s, 0.86 s, 0.93 s, 0.96 s, 1.02 s, 1.09 s, 1.15 s
(21H, 7CH3), 2.10 d (1Н, H1a, J 19.6 Hz), 2.97 d (1H,
H1e, J 15.8 Hz), 3.45 d (1H, H28A, J 6.9 Hz), 3.55 s
(1Н, H19), 3.78 d (1H, H28B, J 8.2 Hz), 6.98–7.20 m
(5H, C6H5), 7.26–7.83 m (10H, C6H4OC6H5 + Hvinyl),
8.03 s (1H, Нpyrazole). Found, %: С 81.80; Н 8.17; N 3.65.
С52Н62N2О3. Calculated, %: С 81.85; Н 8.19; N 3.67.
(1H, H28A, J 7.5 Hz), 3.56 s (1Н, H19), 3.79 d (1H, H28B
,
J 7.6 Hz), 7.30–7.65 m (8H, H3',5' + C6H5 + Hvinyl), 7.75
d (2H, H2',6', J 8.4 Hz), 8.03 s (1H, Нpyrazole). Found, %:
С 73.64; Н 7.64; Br 10.63; N 3.71. С46Н57BrN2О2.
Calculated, %: С 73.68; Н 7.66; Br 10.66; N 3.74.
(E)-2-{[3-(4-Methylphenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}allobetulone (11b). Yield 1.25 g
(81%). White amorphous powder, mp 249–251°C. IR
spectrum, ν, cm–1: 2969–2864 (CH3, CH2), 1669
(E)-2-{[3-(4-Bromophenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}-3-oxolup-20(29)-ene-28-carb-
aldehyde (13а). Yield 1.36 g (79%). White amorphous
1
(C=O), 1140 (C–O–C). H NMR spectrum, δ, ppm:
0.83 s, 0.87 s, 0.95 s, 0.97 s, 1.03 s, 1.10 s, 1.17 s
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 5 2015

BABAK et al.
724
powder, mp 260–262°C. The crystals were grown from
a mixture methylene chloride–ethanol, 1 : 3. IR spec-
trum, ν, cm–1: 2977–2868 (CH3, CH2), 1725 (CHO),
carbaldehyde (13e). Yield 1.14 g (65%). White amor-
phous powder, mp 177–179°C. IR spectrum, ν, cm–1:
2928–2864 (CH3, CH2), 1717 (CHO), 1673 (C=O),
1238 (O–C6H5). 1H NMR spectrum, δ, ppm: 0.82 s, 0.96
s, 1.03 s, 1.08 s, 1.14 s, 1.71 s (18H, 6CH3), 2.91 m (2H,
H1e + H19), 4.70 d (2Н, C29H2, J 24.7 Hz), 6.97–7.17 m
(5H, C6H5), 7.28–7.68 m (8H, H3',5' + C6H5 + Hvinyl),
7.76 d (2H, H2',6', J 7.7 Hz), 8.01 s (1H, Нpyrazole), 9.65
s (1H, Hf28ormyl). Found, %: С 82.03; Н 7.92; N 3.65.
С52Н60N2О3. Calculated, %: С 82.07; Н 7.95; N 3.68.
1
1666 (C=O). H NMR spectrum, δ, ppm: 0.81 s, 0.95
s, 1.02 s, 1.08 s, 1.13 s, 1.71 s, (18H, 6CH3), 2.87 m
(2H, H1e+H19), 4.70 d (2Н, C29H2, J 23.3 Hz), 7.34–
7.56 m (8H, H3',5' + C6H5 + Hvinyl), 7.74 d (2H, H2',6', J
8.1 Hz), 8.00 s (1H, Нpyrazole), 9.63 s (1H, Hf28ormyl).
Found, %: С 73.84; Н 7.40; Br 10.63; N 3.71. С46Н55Br·
N2О2. Calculated, %: С 73.88; Н 7.41; Br 10.68; N 3.75.
(E)-2-{[3-(4-Methylphenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}-3-oxolup-20(29)-ene-28-
carbaldehyde (13b). Yield 1.23 g (78%). White
amorphous powder, mp 118–120°C. IR spectrum, ν,
cm–1: 2929–2864 (CH3, CH2), 1726 (CHO), 1673
(C=O). 1H NMR spectrum, δ, ppm: 0.84 s, 0.97 s, 1.04
s, 1.09 s, 1.15 s, 1.73 s (18H, 6CH3), 2.40 s (3H,
CH3C6H4), 2.91 m (2H, H1e + H19), 4.72 d (2Н, C29H2,
J 24.4 Hz), 7.27 d (2H, H3',5', J 5.4 Hz), 7.33–7.65 m
(6H, C6H5 + Hvinyl), 7.78 d (2H, H2',6', J 7.9 Hz), 8.02 s
(1H, Нpyrazole), 9.65 s (1H, Hf28ormyl). Found, %: С
82.61; Н 8.51; N 4.07. С47Н58N2О2. Calculated, %: С
82.65; Н 8.56; N 4.10.
(E)-2-{[1-(2,6-Dimethylphenyl)-1H-pyrrol-2-yl]-
methylidene}allobetulin (14b). 0.1 g (0.14 mmol) of
α,β-unsaturated ketone 10b was dissolved in 6–8 mL
of a mixture of 2-propanol and dichloromethane, 1 : 1,
and at continuous stirring an excess of sodium tetra-
hydroborate was added. Reaction proceeded for 2–3 h.
The excess of sodium tetrahydroborate was decom-
posed with water at heating to 50–60°C. The separated
precipitate was filtered off and dried in air. White
amorphous powder. Yield 0.088 g (88%), mp 193–
196°C. IR spectrum, ν, cm–1: 3421 (OH), 2924–2860
1
(CH3, CH2), 1235 (C–O–C). H NMR spectrum, δ,
ppm: 0.71 s, 0.77 s, 0.80 s, 0.91 s, 0.92 s, 0.95 s, 1.10 s
(21H, 7CH3), 1.93 d (1Н, H1a, J 8.3 Hz), 1.99–2.16 m
[6H, C6H3(СН3)2], 3.29 d (1H, H1e, J 12.4 Hz), 3.42 d
(1H, H28A, J 7.4 Hz), 3.51 s (1Н, H19), 3.76 d (1H,
H28B, J 8.3 Hz), 3.80 s (1H, Н3), 6,32 s (1Н, Hvinyl),
(E)-2-{[3-(4-Methоxyphenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}-3-oxolup-20(29)-ene-28-
carbaldehyde (13c). Yield 1.34 g (83%). White
amorphous powder, mp 129–131°C. IR spectrum, ν,
cm–1: 2936–2865 (CH3, CH2), 1717 (CHO), 1673
6.45–6.62 m (3H, H3 , 4 , 5
p y r r ol), 7.04–7.21 m (3H, H3',4',5').
Found, %: С 82.71; Н 9.82; N 2.22. С43Н61NО2.
Calculated, %: С 82.77; Н 9.85; N 2.24.
1
(C=O), 1247 (O–CH3). H NMR spectrum, δ, ppm:
0.82 s, 0.95 s, 1.02 s, 1.08 s, 1.14 s, 1.71 s, (18H,
6CH3), 2.90 m (2H, H1e + H19), 3.83 s (3H,
CH3OC6H4), 4.70 d (2Н, C29H2, J 24.4 Hz), 6.97 d
(2H, H3',5', J 7.8 Hz), 7.26–7.66 m (6H, C6H5 + Hvinyl),
7.76 d (2H, H2',6', J 6.9 Hz), 7.99 s (1H, Нpyrazole), 9.65
s (1H, Hf28ormyl). Found, %: С 80.72; Н 8.31; N 4.00.
С47Н58N2О3. Calculated, %: С 80.76; Н 8.36; N 4.01.
Compounds 15a–15e and 16a–16e were similarly
obtained.
(E)-2-{[3-(4-Bromophenyl)-1-phenyl-1H-pyrazol-
4-yl]methylidene}allobetulin (15а). Yield 0.094 g (94%).
White amorphous powder, mp 173–175°C. IR spec-
trum, ν, cm–1: 3433 (OH), 2925–2860 (CH3, CH2), 1224
(C–O–C). 1H NMR spectrum, δ, ppm: 0.75 s, 0.78 s, 0.90–
0.98 m, 1.13 s (21H, 7CH3), 3.01 d (1H, H1e, J 12.5 Hz),
3.44 d (1H, H28A, J 7.6 Hz), 3.51 s (1Н, H19), 3.76 d (1H,
(E)-2-{[3-(1,1'-Biphenyl-4-yl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}-3-oxolup-20(29)-ene-28-
carbaldehyde (13d). Yield 1.04 g (61%). White
amorphous powder, mp 243–245°C. IR spectrum, ν,
cm–1: 2940–2861 (CH3, CH2), 1716 (CHO), 1672
(C=O). 1H NMR spectrum, δ, ppm: 0.84 s, 0.96 s, 1.01
s, 1.09 s, 1.15 s, 1.71 s, (18H, 6CH3), 2.92 m (2H, H1e +
H19), 4.71 d (2Н, C29H2, J 23.7 Hz), 7.33–7.83 m (15H,
C12H9 + C6H5 + Hvinyl), 8.04 s (1H, Нpyrazole), 9.65 s
(1H, Hf28ormyl). Found, %: С 83.80; Н 8.10; N 3.73.
С52Н60N2О2. Calculated, %: С 83.83; Н 8.12; N 3.76.
H
28B, J 7.7 Hz), 3.86 s (1H, H3), 6.52 s (1Н, Hvinyl),
7.28–7.78 m (9H, C6H5 + C6H4), 7.85 s (1H, Нpyrazole).
Found, %: С 73.44; Н 7.88; Br 10.63; N 3.71. С46Н59Br·
N2О2. Calculated, %: С 73.48; Н 7.91; Br 10.63; N 3.73.
(E)-2-{[3-(4-Methylphenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}allobetulin (15b). Yield 0.087 g
(87%). White amorphous powder, mp 181–184°C. IR
spectrum, ν, cm–1: 3467 (OH), 2926–2853 (CH3, CH2),
1231 (C–O–C). 1H NMR spectrum, δ, ppm: 0.73 s, 0.77
s, 0.79 s, 0.91 s, 0.92 s, 0.94 s, 1.11 s (21H, 7CH3),
(E)-2-{[1-Phenyl-3-(4-phenoxyphenyl)-1H-
pyrazol-4-yl]methylidene}3-oxolup-20(29)-ene-28-
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SYNTHESIS OF PYRROL-2-YL- AND PYRAZOL-4-YLMETHYLIDENE DERIVATIVES
725
2.36 s (3H, CH3C6H4), 3.06 d (1H, H1e, J 12.9 Hz),
3.42 d (1H, H28A, J 7.6 Hz), 3.50 s (1Н, H19), 3.75 d
(1H, H28B, J 7.3 Hz), 3.84 s (1H, H3), 6.52 s (1Н,
trum, δ, ppm: 0.74 s, 0.99 s, 1.12 s, 1.67 s, (18H, 6CH3),
2.35 s (1H, H1a), 2.94 d (1H, H1e, J 12.9 Hz), 3.31 d
(1Н, H28A, J 10.7 Hz), 3.77 d (1Н, H28B, J 10.8 Hz),
3.86 s (1H, H3), 4.61 d (2Н, C29H2, J 19.5 Hz), 6,50 s
(1Н, Hvinyl), 7.27–7.59 m (5H, C6H5), 7.62–7.78 m
(4H, C6H4), 7.81 s (1H, Нpyrazole). Found, %: С 73.45;
Н 7.91; Br 10.61; N 3.71. С46Н55BrN2О2. Calculated,
%: С 73.48; Н 7.91; Br 10.63; N 3.73.
Hvinyl), 7.11–7.78 m (9H, C6H5 + C6H4), 7.84 s (1H,
Нpyrazole). Found, %: С 82.10; Н 9.03; N 4.05.
С47Н62N2О2. Calculated, %: С 82.17; Н 9.10; N 4.08.
(E)-2-{[3-(4-Methoxyphenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}allobetulin (15c). Yield 0.093 g
(93%). White amorphous powder, mp 204–206°C. The
crystals were grown from a mixture methylene chlo-
ride–ethanol, 1 : 3. IR spectrum, ν, cm–1: 3421 (OH),
2927–2862 (CH3, CH2), 1248 (O–CH3), 1174 (C–O–C).
1H NMR spectrum, δ, ppm: 0.73 s, 0.77 s, 0.90 s,
0.92 s, 0.95 s, 1.11 s (21H, 7CH3), 3.05 d (1H, H1e, J
12.2 Hz), 3.42 d (1H, H28A, J 7.8 Hz), 3.50 s (1Н, H19),
(E)-2-{[3-(4-Methylphenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}lup-20(29)-ene-3,28-diol (16b).
Yield 0.090 g (89%). White amorphous powder, mp
205–207°C. IR spectrum, ν, cm–1: 3360 br (OH), 2947–
1
2865 (CH3, CH2). H NMR spectrum, δ, ppm: 0.76 s,
1.01 s, 1.13 s, 1.68 s (18H, 6CH3), 2.38 s (3H, 4'-CH3),
3.01 d (1H, H1e, J 12.8 Hz), 3.32 d (1Н, H28A, J 10.9 Hz),
3.79 d (1Н, H28B, J 11.4 Hz), 3.87 s (1H, H3), 4.62 d
(2Н, C29H2, J 19.8 Hz), 6.52 s (1Н, Hvinyl), 7.22 d (2H,
H3',5', J 8.1 Hz), 7.27–7.70 m (5H, C6H5), 7.75 d (2H,
H2',6', J 8.7 Hz), 7.83 s (1H, Нpyrazole). Found, %: С
82.11; Н 9.08; N 4.07. С47Н62N2О2. Calculated, %: С
82.17; Н 9.10; N 4.08.
3.75 d (1H, H28B, J 7.8 Hz), 3.82 s (4H, H3
+
CH3OC6H4), 6.51 s (1Н, Hvinyl), 6.86–7.78 m (9H,
C6H5 + C6H4), 7.83 s (1H, Нpyrazole). Found, %: С
80.29; Н 8.83; N 3.97. С47Н62N2О3. Calculated, %: С
80.30; Н 8.89; N 3.98.
(E)-2-{[3-(1,1'-Biphenyl-4-yl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}allobetulin (15d). Yield 0.080 g
(80%). White amorphous powder, mp 174–176°C. IR
spectrum, ν, cm–1: 3430 (OH), 2924–2860 (CH3, CH2),
1224 (C–O–C). 1H NMR spectrum, δ, ppm: 0.76 s, 0.80
s, 0.91 s, 0.95 s, 1.12 s (21H, 7CH3), 3.06 d (1H, H1e, J
12.1 Hz), 3.42 d (1H, H28A, J 7.8 Hz), 3.50 s (1Н, H19),
3.75 d (1H, H28B, J 7.8 Hz), 3.87 s (1H, H3), 6.59 s
(1Н, Hvinyl), 7.26–7.88 m (14H, C12H9 + C6H5), 7.90 s
(1H, Нpyrazole). Found, %: С 83.35; Н 8.61; N 3.73.
С52Н64N2О2. Calculated, %: С 83.38; Н 8.61; N 3.74.
(E)-2-{[3-(4-Methoxyphenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}lup-20(29)-ene-3,28-diol (16c).
Yield 0.089 g (88%). White amorphous powder, mp
133–135°C. IR spectrum, ν, cm–1: 3311 br (OH), 2939–
1
2867 (CH3, CH2), 1248 (O–CH3). H NMR spectrum,
δ, ppm: 0.73 s, 0.98 s, 1.01 s, 1.65 s (18H, 6CH3), 2.34
s (1H, H1a), 2.89 d (1H, H1e, J 14.0 Hz), 3.29 d (1Н,
H28A, J 10.6 Hz), 3.59–3.99 m (5Н, H28B, H3, CH3O),
4.60 d (2Н, C29H2, J 20.8 Hz), 6.48 s (1Н, Hvinyl), 6.92
d (2H, H3',5', J 9.0 Hz), 7.46 d (2H, H2',6', J 7.6 Hz),
7.63–7.85 m (5H, C6H5), 7.95 s (1H, Нpyrazole). Found,
%: С 80.29; Н 8.81; N 3.97. С47Н62N2О3. Calculated,
%: С 80.30; Н 8.89; N 3.98.
(E)-2-{[1-Phenyl-3-(4-phenoxyphenyl)-1H-pyra-
zol-4-yl]methylidene}allobetulin (15e). Yield 0.082 g
(82%). White amorphous powder, mp 138–140°C. IR
spectrum, ν, cm–1: 3430 (OH), 2924–2860 (CH3, CH2),
(E)-2-{[3-(1,1'-Biphenyl-4-yl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}lup-20(29)-ene-3,28-diol (16d).
Yield 0.085 g (85%). White amorphous powder, mp
270–272°C. IR spectrum, ν, cm–1: 3420 br (OH), 2936–
1
1238 br (O–C6H5, C–O–C). H NMR spectrum, δ,
ppm: 0.72 s, 0.77 s, 0.90 s, 0.92 s, 0.95 s, 1.11 s (21H,
7CH3), 3.03 d (1H, H1e, J 13.1 Hz), 3.42 d (1H, H28A, J
7.7 Hz), 3.50 s (1Н, H19), 3.75 d (1H, H28B, J 7.8 Hz),
3.83 s (1H, H3), 6,53 s (1Н, Hvinyl), 6.95–7.15 m (5H,
OC6H5), 7.27–7.79 m (9H, C6H5 + C6H4), 7.85 s (1H,
1
2864 (CH3, CH2). H NMR spectrum, δ, ppm: 0.78 s,
1.00 s, 1.13 s, 1.67 s (18H, 6CH3), 2.36 s (1H, H1a), 3.00 d
(1H, H1e, J 13.7 Hz), 3.32 d (1Н, H28A, J 10.5 Hz), 3.78
d (1Н, H28B, J 11.3 Hz), 3.88 s (1H, H3), 4.61 d (2Н,
C29H2, J 20.3 Hz), 6.58 s (1Н, Hvinyl), 7.28–7.94 m (15H,
C12H9 + C6H5 + Hpyrazole). Found, %: С 83.37; Н 8.60; N
3.73. С52Н64N2О2. Calculated, %: С 83.38; Н 8.61; N 3.74.
Нpyrazole). Found, %: С 81.60; Н 8.37; N 3.65.
С52Н64N2О3. Calculated, %: С 81.63; Н 8.43; N 3.66.
(E)-2-{[3-(4-Bromophenyl)-1-phenyl-1H-pyra-
zol-4-yl]methylidene}lup-20(29)-ene-3,28-diol (16a).
Yield 0.089 g (89%). White amorphous powder, mp
178–180°C. The crystals were grown from a mixture
methylene chloride–ethanol, 1 : 3. IR spectrum, ν, cm–1:
(E)-2-{[1-Phenyl-3-(4-phenoxyphenyl)-1H-pyra-
zol-4-yl]methylidene}lup-20(29)-ene-3,28-diol (16e).
Yield 0.091 g (91%). White amorphous powder, mp
245–247°C. IR spectrum, ν, cm–1: 3430 br (OH), 2939–
1
3419 (OH) br, 2940–2867 (CH3, CH2). H NMR spec-
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 51 No. 5 2015

BABAK et al.
726
1
5. Kutulya, L.A., Kondratyuk, Zh.O., Novikova, N.B.,
Shkol’nikova, N.I., Yaremenko, F.G., Vakula, V.M.,
and Pivnenko, M.S., Ukrainian Patent no. 85812, 2008;
Byull. Prom. Sobstv., 2009, no. 4.
2866 (CH3, CH2), 1237 (O–C6H5). H NMR spectrum,
δ, ppm: 0.73 s, 0.99 s, 1.11 s, 1.65 s (18H, 6CH3), 2.37
s (1H, H1a), 2.97 d (1H, H1e, J 13.6 Hz), 3.31 d (1Н,
H28A, J 8.8 Hz), 3.77 d (1Н, H28B, J 10.1 Hz), 3.85 s
(1H, H3), 4.60 d (2Н, C29H2, J 20.6 Hz), 6.51 s (1Н,
Hvinyl), 6.95–7.80 m (14H, C12H9O + C6H5), 7.81 s
(1H, Нpyrazole). Found, %: С 81.57; Н 8.40; N 3.65.
С52Н64N2О3. Calculated, %: С 81.63; Н 8.43; N 3.66.
6. Shkol’nikova, N.I., Sheshenko, Zh.O., Vakula, V.M.,
Vashchenko, O.V., Novikova, N.B., Yaremenko, F.G.,
Lipson, V.V., Rosahl’, O.D., and Taidakov, I.V.,
Ukrainian Patent no. 106657, 2012; Byull. Prom.
Sobstv., 2014, no. 18.
The twisting power (β) of compounds 8a, 8b, 11a–
11e, 13a–13e, 15a–15e and 16a–16e was estimated by
the pitch of the helix Р, using Grange–Cano method by
7. Doane, J.W., Khan, A.A., and Seed, A.J., US Patent
no. 6830789, 2004; Chem. Abstr., 2004, vol. 136,
no. 61589.
procedure [22]. These indices are related as β = (РTred
·
8. Doane, J.W., Khan, A.A., Shiyanovskaya, I., and
Green, A., US Patent no. 7236151, 2004; Chem. Abstr.,
2005, vol. 143, no. 163250.
c · r)–1, where РTred is the pitch of the helix at the
reduced temperature Tred [Tred = (Tіso + 273) · 0.98 –
273], Tіso is the temperature of the phase transition
cholesteric–isotropic liquid, c is the substance concentra-
tion, r is the enantiomeric purity (for all the studied
compounds r = 1).
9. Parri, O., Nolan, P., Farrand, L., and May, A., US Patent
no. 6217792, 2001; Chem. Abstr., 2001, vol. 128,
no. 134449.
10. Bauer, M., Boeffel, Ch., Kuschel, F., and Zaschke, H.,
J. Soc. Inform. Display, 2006, vol. 14, p. 805.
The X-ray diffraction analysis of all studied
compounds 8е, 11с, 13а, 15с and 16а was carried out
on a diffractometer Xcalibur-3 (MoKα radiation, ССD-
detector, graphite monochromator, ω-scanning, 2θmax
60°). The structures were solved by the direct method
using SHELXTL software [16]. The positions of hydro-
gen atoms were found from the difference synthesis of
electron density and refined in the rider model. Uiso = nUeq
of the nonhydrogen atom attached to the hydrogen (n = 1.5
for methyl groups, 1.2 for the other hydrogen atoms).
The extinction for the molecules 13а and 16а was
taken into account by semiempiric method using
multiscanning results. The crystallographic data and
experimental parameters are collected in Table 4.
11. Goh, M. and Akagi, K., Liq. Cryst., 2008, vol. 35,
p. 953.
12. Motoyama, Y. and Johno, M., US Patent no. 6699532,
2003; Chem. Abstr., 2004, vol. 140, no. 84718.
13. Puhua, W., Jiong, Z., Qingqing, M., Bakela, N., Robert, T.J.,
and Huchen, Z., Eur. J. Med. Chem., 2014, vol. 81,
p. 59.
14. Massa, S., Corelli, F., and Stefancich, G., J. Heterocycl.
Chem., 1981, vol. 18, p. 829.
15. Krishna, M.S., Shripal, M.Ch., and Shanawaz, N.N.,
Org. Chem. Indian J., 2009, vol. 5, p. 88.
16. Sheldrick, G.M., Acta Cryst., 2008, vol. A64, p. 112.
17. Babak, N.L., Gella, I.M., Semenenko, A.N.,
Shishkina, S.V., Shishkin, O.V., Musatov, V.I.,
and Lipson. V.V., Russ. J. Org. Chem., 2014, vol. 50,
p. 1048.
Atomic coordinates and complete data of bond
lengths and bond angles are deposited in the
Cambridge Crystallographic Data Center (e-mail:
deposit@ccdc.cam.ac.uk), the corresponding CCDC
numbers are given in Table 4.
18. Kutulya, L.A., Pivnenko, N.S., Nemchenko, I.B.,
Khandrimailova, T.V., Semenkova, G.P., Biba, V.I., and
Tishchenko, V.G., Zh. Obshch. Khim., 1987, vol. 57,
p. 397.
19. Gella, I.M., Babak, M.L., Shkol’nikova, N.I.,
Novikova, N.B., and Lipson, V.V., Ukrainian
Patent no. 105617, 2013; Byull. Prom. Sobstv., 2014,
no. 10.
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