New Chiral 3-aryl-7-arylmethylidene-3,3a,4,5,6,7-hexahydro-indazoles: Synthesis, structure, and twisting power in nematic liquid crystals

Article abstract of DOI:10.1134/S1070428010080154

(3R)-2,6-Bis(arylmethylidene)-3-methylcyclohexanones and 3-(4-X-aryl)-7-(4-X-arylmethylidene)- 3,3a,4,5,6,7-hexahydro-2,6- and -2,4-dimethyl-2H-indazoles (X = Cl, HO, AlkO, AlkOCO, MeOC₆H ₄COO) as potential chiral additives to liquid

Full text of DOI:10.1134/S1070428010080154

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2010, Vol. 46, No. 8, pp. 1207–1213. © Pleiades Publishing, Ltd., 2010.
Original Russian Text © V.V. Abakumov, N.S. Pivnenko, L.A. Kutulya, I.S. Konovalova, A.D. Roshal’, N.B. Novikova, O.V. Shishkin, 2010, published in
Zhurnal Organicheskoi Khimii, 2010, Vol. 46, No. 8, pp. 1205–1211.
New Chiral 3-Aryl-7-arylmethylidene-3,3a,4,5,6,7-hexahydro-
indazoles: Synthesis, Structure, and Twisting Power
in Nematic Liquid Crystals
V. V. Abakumov, N. S. Pivnenko, L. A. Kutulya, I. S. Konovalova, A. D. Roshal’,
N. B. Novikova, and O. V. Shishkin
Institute of Single Crystals, National Academy of Sciences of Ukraine, pr. Lenina 60, Khar’kov, 61001 Ukraine
e-mail: kutulya@isc.kharkov.com
Received December 7, 2009
Abstract—(3R)-2,6-Bis(arylmethylidene)-3-methylcyclohexanones and 3-(4-X-aryl)-7-(4-X-arylmethylidene)-
3,3a,4,5,6,7-hexahydro-2,6- and -2,4-dimethyl-2H-indazoles (X = Cl, HO, AlkO, AlkOCO, MeOC6H4COO) as
potential chiral additives to liquid crystalline systems were synthesized starting from (3R)-3-methylcyclo-
hexanone. Relations between the twisting power and molecular structure of the synthesized compounds are
discussed.
DOI: 10.1134/S1070428010080154
Modern compositions for imaging devices based on
liquid crystalline materials usually contain several
components, among which chiral additives are impor-
tant. Such additives are capable of inducing formation
in mesophase of helical supramolecular structures via
transformation of nematic (N) and smectic-C (SmC)
phases into cholesteric and ferroelectric SmC* [1–4].
Diversity of requirements to chiral components of
liquid crystals makes search for new chiral additives
an important problem. Biological activity of substitu-
ted hexahydroindazoles and their N-methyl and sul-
fonyl analogs was studied [5–8], and their chemical
properties were also examined.
The present study was aimed at synthesizing photo-
stable chiral additives with a strong twisting power on
the basis of (3R)-3-methylcyclohexanone (I). A general
procedure for the synthesis of 2-substituted hexahydro-
indazoles is based on reaction of benzylidenecyclo-
hexanones with hydrazine derivatives in the presence
of hydrochloric [5, 9] or acetic acid [6], as well as in
the absence of a catalyst in alcoholic medium [7]. Syn-
theses under basic conditions are less common [10]; in
these cases, alternative products are formed [11–13].
ylidene)cyclohexanones readily reacted with hydrazine
and methylhydrazine, whereas the former failed to
react with phenylhydrazine and thiosemicarbazide.
Hexahydroindazoles obtained by the reaction with hy-
drazine readily undergo oxidation with atmospheric
oxygen. Even though N-acylation stabilizes these com-
pounds, their twisting power in liquid crystals strongly
weakens. We considered compounds III and IV as
target components of liquid crystalline compositions.
They were synthesized under conditions of base catal-
ysis using triethylamine (in the synthesis of IIIb) [14]
or excess methylhydrazine (IIIa–IIIe) to avoid tarring
in acid medium. In the general case, the reaction with
methylhydrazine gives two groups of regioisomeric
products III and IV (Scheme 1), depending on the
double bond (C2=C or C6=C) involved in the formation
of pyrazole fragment; in addition, cis–trans isomerism
with respect to the C3–C3a bond is possible; therefore,
eight regio- and stereoisomers may be formed.
1
In fact, the H NMR data showed the presence in
the reaction mixtures of appreciable amounts of three
or four compounds, which were identified by the sig-
nal from the methyl group on the cyclohexane ring. In
the reaction with ketone IIb we succeeded in isolating
both regioisomers IIIb and IVb as individual sub-
stances, and their structure was proved by X-ray anal-
ysis [15]. The chemical shifts of protons in the CH3
We found that the reactivity of initial ketones II
toward various hydrazine derivatives is considerably
lower than the reactivity of 2,6-bis(arylmethylidene)
cyclohexanones. Both ketones II and 2,6-bis(arylmeth-
1207

ABAKUMOV et al.
1208
Scheme 1.
(1) MeOH, gaseous HCl
O
O
(R = OH)
(2) DMSO, KOH
(R = OAlk, Hlg)
CHO
+
Me
R
R
Me
R
I
IIa–IIe
Me
Me
N
*
N
3
N
N
*
*
MeNHNH2, i-PrOH
*
3a
7
6
R
+
R
4
*
5
*
R
Me
Me
R
IIIa–IIIe
IVb, IVe
Me
*
N
*
O
N
R
O
IIIa
O
*
R
O
Me
Va–Ve
II, III, R = HO (a), MeO (b), EtO (c), PrO (d), Cl (e); IV, R = MeO (b), Cl (e); V, R = Me (a), Et (b),
Pr (c), Bu (d), C5H11 (e), 4-MeOC6H4 (f).
The structure of compounds Va–Vf was determined
groups of these isomers differed considerably, δ 1.314
and 0.665 ppm, respectively. We failed to separate
product mixtures formed in the reactions with other
ketones (R = F, Cl, Br, PhCH2O, Et2N). The fractions
of particular regioisomers in these mixtures may be
estimated by the intensities of the 3-CH3 signals.
1
using H NMR spectroscopy (see Experimental), mass
1
spectrometry, and elemental analysis. In the H NMR
spectra of Va–Vf we observed a doublet signal from
the methyl group (δ 1.31–1.29 ppm), a doublet from
the 3-H proton (δ 3.63–3.67 ppm), and multiplets in
the region δ 1.87–1.65 ppm from methylene protons in
the cyclohexane ring. The singlet at δ 2.79 ppm be-
longs to the N-methyl group, and multiplets at δ 3.26
and 2.84–2.76 ppm originate from 6-H and 3a-H, re-
spectively. The =CH– proton resonates as a broadened
singlet at 6.99–7.03 ppm. Doublets in the region
δ 7.44–7.05 ppm (δ 8.16–6.99 ppm for compound Vg)
correspond to 8 (16) aromatic protons. Extension of
the aliphatic substituent is accompanied by appearance
of multiplet signals corresponding to methylene pro-
tons at δ 2.56, 1.75, and 1.45–1.39 ppm, while shield-
ing of protons in the terminal methyl group gradually
increases (δ 1.27–0.93 ppm). The structure of the ali-
phatic substituent almost does not affect the position of
aromatic proton signals and signals from protons in the
indazole fragment. The chemical shifts of protons in
the methylene and methyl groups in the aliphatic side
chains attached to benzene rings at different sides of
the indazole fragment differ by 1.0–2.5 Hz.
The twisting power of particular isomers may be
1
estimated if their ratios (from the H NMR spectra)
and weight-average twisting powers of two mixtures
are known. Two mixtures with different compositions
were obtained by recrystallization, and their twisting
powers β were measured. On the basis of these data we
estimated β values for isomers IIIe and IVe which
showed a satisfactory agreement with those calculated
for couple IIIb/IVb (see table).
Twisting power β, μm–1 mol–1, of compounds II–IV in
nematic solvent, 4′-pentylbiphenyl-4-carbonitrile
Comp. no. –β Comp. no. –β Comp. no. –β
IIa
IIb
IIc
IId
IIe
~11~
17
20
22
16
IIIb
IIIc
IIId
IIIe
39
39
45
IVb
IVe
12
Starting from chiral ketone IIa with 4-hydroxyben-
zylidene fragments, we synthesized a series of acyl
~33~
0~8~
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NEW CHIRAL 3-ARYL-7-ARYLMETHYLIDENE-3,3a,4,5,6,7-HEXAHYDROINDAZOLES:
1209
derivatives V. Extension of the alkyl side chain was
accompanied by increase in |β| which was equal to
57 μm–1 mol–1 for R = C5H11; p-methoxybenzoic
acid derivative was characterized by a β value of
71 μm–1 mol–1. None of the synthesized compounds
exhibited mesomorphic properties. Materials possess-
ing highly effective optical properties were developed
on the basis of liquid crystal E63 (Merck) containing
chiral additives III at a small concentration.
We also made an attempt to reveal a relation be-
tween the structure of chiral additives and their twist-
ing power. First of all, strong difference in the twisting
powers between regioisomeric compounds IIIb/IVb
and IIIe/IVe should be noted. The regioisomers in the
above couples differ by the position of chiral center
(and methyl group attached thereto) relative to the
highly polarizable bond sequence, as well as by the
length of that sequence. The bond chain in molecules
IIIb and IIIe includes the benzylidene moiety and
N-methyl-substituted enehydrazone fragment. The
chain of conjugated atoms directly adjoining the chiral
center in molecules IVb and IVe is considerably
shorter. The second structural specificity determining
twisting power of the examined chiral additives is
intrinsic helical chirality of the above conjugation
chain. As follows from the X-ray diffraction data, the
torsion angle N1C1C2C8 in molecule IIIb is fairly large
[31.1(3)°]; the torsion angle C2C8C9C10 is character-
ized by a similar magnitude [26.4(4)°] and the same
sign of twist (Fig. 1).
C15
C4
C5
C3
C2
C18
C10
C11
C12
C17
C16
C6
C1
N1
C19
C9
O1
C7
C8
C20
C13
C21
N2
C14
C22
Fig. 1. Structure of the molecule of 4-[(3S,3aR,6R,7E)-7-(4-
hydroxybenzylidene)-2,6-dimethyl-3,3a,4,5,6,7-hexahydro-
2H-indazol-3-yl]phenol (IIIa) according to the X-ray dif-
fraction data.
especially important for chiral structures which thus
acquire intrinsic helical chirality. We can presume that
interrelated variations of the intramolecular parameters
ω and φ are responsible for the observed strong twist-
ing power of the chiral compounds under study.
Extension of the conjugated fragment system, e.g.,
by one ring as in compound Vf, leads to considerable
increase in |β| as compared to aliphatic acid esters.
Extension of the alkyl chain is accompanied by smaller
increase in the twisting power |β| which attains a value
of 57 μm–1 mol–1. The twisting power slightly in-
creases in going from methoxy- to ethoxy- and then to
propoxy-substituted derivatives. These findings reflect
fairly weak increase of polarizability of the system
upon extension of the alkyl chain as compared to intro-
duction of additional benzene rings.
The presence of a methyl group at the chiral center
and its position in the chain of conjugated fragments
play an important role in the appearance of strong
induced supramolecular twisting in LC systems doped
with chiral additives. The endocyclic bond angle
C3C2C8 [126.1(2)°], as well as the outer (with respect
to the hexahydroindazole fragment) bond angles
C2C8C9 [131.5(2)°] and C8C9C10 [125.8(2)°] are appre-
ciably larger than the standard bond angles at sp2-hy-
bridized atoms. Correspondingly, the torsion angles
about the C3–C2 [C15C3C2C8 –97.2(3)°], C2–C8
[C3C2C8C9 3.6(4)°], and C8–C9 bonds [C2C8C9C10
26.4(4)°] strongly deviate from 0 or 180°, i.e., from the
torsion angles typical of planar conjugated molecular
fragments. Small twisting of the double C2=C8 bond
should also be noted. A combination of the above geo-
metric parameters determines intrinsic helical chirality
of the examined structures. Analogous structural speci-
ficity was observed previously for some other α,β-un-
saturated ketones with s-configuration of the enone
fragment fixed by six-membered ring [16–19]. This is
a
c
0
b
Fig. 2. Crystal packing of 4-[(3S,3aR,6R,7E)-7-(4-hydroxy-
benzylidene)-2,6-dimethyl-3,3a,4,5,6,7-hexahydro-2H-inda-
zol-3-yl]phenol (IIIa) molecules.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

ABAKUMOV et al.
1210
It should be emphasized that each torsion angle
solubility can be used in modern display technologies,
namely in display devices whose operation is based on
selective reflection of light in the visible region of the
spectrum.
about the C3–C2, C8–C9, and C9–C10 bonds has a defi-
nite sign at a given fixed conformation of the cyclo-
hexane ring. Therefore, twisting of the above fragment
is stereospecific, and the sign of twist remains constant
in the series of liquid crystals doped by the compounds
under study.
EXPERIMENTAL
1
The H NMR spectra were recorded on Varian
Obviously, conformational homogeneity of chiral
additives is a quite important factor, for inversion of
the cyclohexane ring is accompanied by change of the
signs of the above listed torsion angles to opposite.
Therefore, such conformers are expected to induce
twisting in the opposite direction. As a result, statistical
twisting power of conformationally equilibrium sys-
tems should be reduced. Insofar as structurally related
chiral compounds with the same character of molec-
ular twist give rise to helical structures with the same
sign in liquid crystals [18, 19], the above analysis of
relations between the twisting power of chiral addi-
tives in liquid crystals and geometric parameters of
molecules (determined by X-ray analysis of crystals)
may be regarded as appropriate.
Sharply reduced twisting power of hydroxy-substi-
tuted chiral additive IIIa as compared to alkoxy ana-
logs IIIb–IIId attracts interest. As follows from the
X-ray diffraction data, molecules IIIa in crystal are
involved in two types of intermolecular hydrogen
bonds: H–O···H–O and –OH···N=C. These hydrogen
bonds are characterized by almost similar lengths,
1.93(3) (OH···O) and 1.95(3) Å (OH···N=), and are
responsible for the formation of stacks along the (100)
crystallographic axis (Fig. 2). The twisting power of
chiral additive IIIa is considerably lower than those of
compounds IIIb-IIId having terminal alkoxy groups
(see table). Obviously, this difference results from dis-
ordering due to association of the chiral additive in the
nematic phase.
The structural parameters determined by X-ray
analysis also provide important information on the
electronic structure of molecules containing a dihydro-
pyrazole heteroring. The bond angles at N2 in the pyra-
zole ring of molecule IIIa approach values typical of
tetrahedral configuration, and the sum of the bond
angles Σω(N) is 330.8°. This value is even smaller
than that found previously [15] for methoxy-substi-
tuted analog IIIb (the same regioisomer, 333.6°). Un-
doubtedly, the observed pattern reflects differences in
intramolecular electronic interactions of terminal elect-
ron-donor substituents in compounds IIIa and IIIb.
Mercury VX-200 (200 MHz) and Varian Mercury-400
(400 MHz) spectrometers; the chemical shifts were
measured relative to tetramethylsilane. The IR spectra
were recorded in KBr on a Bruker IFS66 spectrometer.
The melting points were determined in open capillaries
using a PTP(M) melting point apparatus. The progress
of reactions was monitored by TLC on Silufol UV-254
plates using ethyl acetate–heptane (2:3) as eluent. The
purity of the isolated compounds was checked by
liquid chromatography on a Bishoff instrument;
ProntoSIL 120-5-C18 reversed-phase column, water–
acetonitrile azeotrope as eluent. The specific optical
rotations were measured in ethyl acetate on a Perkin–
Elmer 343 polarimeter. The mass spectra (electron
impact, 70 eV) were obtained on a Varian 1200 L GS–
MS instrument.
X-Ray analysis of compound IIIa. Triclinic
crystal system, space group P1; C22H24N2O2; unit cell
parameters (20°C): a = 5.507(1), b = 9.540(1), c =
9.981(2) Å; α = 64.11(2), β = 84.03(2), γ = 84.09(1)°;
V = 468.2(1) Å3; Mr = 348.43; Z = 1; dcalc = 1.236 g×
cm–3; μ(MoKα) = 0.079 mm–1; F(000) = 186. The unit
cell parameters and intensities of 2808 reflections
(1886 independent reflections with Rint = 0.011) were
measured on an Xcalibur-3 diffractometer (MoKα ir-
radiation, CCD detector, graphite monochromator,
ω-scanning, 2θmax = 50°). The structure was solved by
the direct method using SHELXTL software package
[20]. The positions of hydrogen atoms were deter-
mined by difference syntheses of electron density and
were refined according to the riding model with Uiso
=
nUeq for the non-hydrogen atom to which the given
hydrogen atom is attached (n = 1.5 for methyl hydro-
gen atoms and n = 1.2 for the other hydrogen atoms).
The positions of hydrogen atoms in the hydroxy
groups were refined in isotropic approximation. The
absolute configuration was determined assuming (3R)
configuration of the chiral center, which cannot change
in the synthesis of compound IIIa. The positions of
non-hydrogen atoms were refined by F2 in anisotropic
approximation by the full-matrix least-squares proce-
dure to wR2 = 0.069 (for 1771 reflections) and R1 =
0.026 [for 1632 reflections with F > 4σ(F), S = 1.044].
New effective chiral additives possessing a strong
twisting power, increased photostability, and sufficient
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NEW CHIRAL 3-ARYL-7-ARYLMETHYLIDENE-3,3a,4,5,6,7-HEXAHYDROINDAZOLES:
1211
The coordinates of atoms and the complete sets of
bond lengths and bond angles were deposited to
the Cambridge Crystallographic Data Centre (entry
no. CCDC 742609).
Initial ketones IIb–IIe [21] and IIa [22, 23] were
synthesized according to known methods. The twisting
power was measured in 4′-pentylbiphenyl-4-carbo-
nitrile according to the procedure described in [24].
6-H), 3.55 m (1H, 3a-H), 4.03 q (4H, OCH2), 6.79 s
3
(1H, 9-H), 6.93 m (4H, Harom, J = 8.7 Hz), 7.32 m
(4H, Harom, 3J = 8.7 Hz). Mass spectrum, m/z 404 [M]+.
Found, %: C 77.08; H 7.99; N 6.97. C26H32N2O2. Cal-
culated, %: C 77.19; H 7.97; N 6.92. M 404.55.
(3S,3aR,6R,7E)-2,6-Dimethyl-7-(4-propoxyben-
zylidene)-3-(4-propoxyphenyl)-3,3a,4,5,6,7-hexa-
hydro-2H-indazole (IIId) was synthesized in a similar
way. Yield 160 mg (37%), mp 126–128°C, [α]D =
–702.97°. IR spectrum, ν, cm–1: 3421, 2931, 1604,
4-[(3S,3aR,6R,7E)-7-(4-Hydroxybenzylidene)-
2,6-dimethyl-3,3a,4,5,6,7-hexahydro-2H-indazol-3-
yl]phenol (IIIa). Methylhydrazine, 2.2 ml (39 mmol),
was added to a solution of 1.51 g (4.7 mmol) of ketone
IIa in 20 ml of methanol, the mixture was heated for
1 h under reflux, and a colorless solid separated. The
mixture was cooled to room temperature, and the
precipitate was filtered off and washed with a small
amount of methanol. The product was pure according
1
1508, 1242. H NMR spectrum (CDCl3), δ, ppm:
3
1.04 m (6H, CH3), 1.30 d (3H, CH3, J = 7.1 Hz),
1.64–1.88 m (4H, 4-H, 5-H), 1.81 m (4H, CH2), 2.77 s
(3H, NCH3), 2.79 m (1H, 3a-H), 3.28 m (1H, 6-H),
3.54 d (1H, 3-H, 3J = 14.0 Hz), 3,93 t (4H, OCH2, 3J =
3
6.5 Hz), 6.87 d (2H, Harom, J = 8.7 Hz), 6.89 d (2H,
Harom, 3J = 8.7 Hz), 6.97 s (1H), 7.30 d (2H, Harom, 3J =
3
8.7 Hz), 7.33 d (2H, Harom, J = 8.7 Hz). Mass spec-
1
to the H NMR data. Yield 0.37 g (23%), mp 254–
trum: m/z 432 [M]+. Found, %: C 77.65; H 8.51;
N 6.40. C28H36N2O2. Calculated, %: C 77.74; H 8.39;
N 6.48. M 432.61.
255°C. IR spectrum, ν, cm–1: 3367, 2955, 2786, 1606,
1
1514, 1444, 1362, 1271, 1244, 1168. H NMR spec-
3
trum (DMSO-d6), δ, ppm: 1.20 d (3H, CH3, J =
4-[(3S,3aR,6R,7E)-7-(4-Acetoxybenzylidene)-2,6-
dimethyl-3,3a,4,5,6,7-hexahydro-2H-indazol-3-yl]-
phenyl acetate (Va). Compound IIIa, 0.12 g
(0.35 mmol), was dispersed in 3 ml of tetrahydro-
furan, 13 mg (0.11 mmol) of 4-dimethylaminopyridine
and 0.050 ml (0.88 mmol) of acetic acid were added in
succession, the mixture was cooled to 0°C with an ice–
water mixture, and 0.29 g (1.41 mmol) of N,N′-dicy-
clohexylcarbodiimide was added. The mixture was
stirred for 24 h and filtered through a 2-cm layer of
silica gel (Merck 60), and the sorbent was washed with
THF. The solvent was distilled off on a rotary evap-
orator, and the residue was recrystallized from propan-
2-ol. Yield 80 mg (53%), mp 193–195°C, [α]D =
–696.53. IR spectrum, ν, cm–1: 2927, 2956, 2833,
6.9 Hz), 1.56–1.67 m (4H, 4-H, 5-H), 2.58 s (3H,
NCH3), 2.62 m (1H, 3a-H), 3.18 m (1H, 6-H), 3.47 d
3
(1H, 3-H, J = 14.2 Hz), 6.75 m (4H, Harom), 6.79 s
(1H), 7.19 m (2H, Harom), 7.23 m (2H, Harom), 9.38 s
(1H, OH), 9.61 s (1H, OH). Found, %: C 75.58;
H 6.84; N 7.95. C22H24N2O2. Calculated, %: C 75.83;
H 6.94; N 8.04.
(3S,3aR,6R,7E)-7-(4-Methoxybenzylidene)-3-(4-
methoxyphenyl)-2,6-dimethyl-3,3a,4,5,6,7-hexa-
hydro-2H-indazole (IIIb) and (3S,3aR,4R,7E)-
7-(4-methoxybenzylidene)-3-(4-methoxyphenyl)-
2,4-dimethyl-3,3a,4,5,6,7-hexahydro-2H-indazole
(IVb) were synthesized according to the procedure
described previously [14].
1
1749, 1506, 1440, 1369, 1220, 1191. H NMR spec-
(3S,3aR,6R,7E)-7-(4-Ethoxybenzylidene)-3-
(4-ethoxyphenyl)-2,6-dimethyl-3,3a,4,5,6,7-hexa-
hydro-2H-indazole (IIIc). Methylhydrazine, 0.35 ml
(6.5 mmol), was added to a suspension of 300 mg
(0.8 mmol) of ketone IIc in 5 ml of methanol, and the
mixture was heated for 45 min under reflux. The
precipitate dissolved, and the originally yellow mixture
turned lighter. The mixture was evaporated under
reduced pressure, and the residue was recrystallized
from propan-2-ol. Yield 140 mg (33%), mp 123–
125°C. IR spectrum, ν, cm–1: 3392, 2924, 1510, 1606,
1440, 1392, 1249, 1169, 1117, 1050, 921, 876, 805,
3
trum (CDCl3), δ, ppm, 1.29 d (3H, CH3, J = 7.2 Hz),
1.64–1.88 m (4H, 4-H, 5-H), 2.30 s (6H, CH3CO),
2.79 s (3H, NCH3), 2.80 m (1H, 3a-H), 3.25 m (1H,
3
6-H), 3.63 d (1H, 3-H, J = 14.1 Hz), 6.98 s (1H,
3
CH=C), 7.07 d (2H, Harom, J = 8.4 Hz), 7.09 d (2H,
3
3
H
arom, J = 8.4 Hz), 7.35 d (2H, Harom, J = 8.4 Hz),
3
7.44 d (2H, Harom, J = 8.4 Hz). Mass spectrum:
m/z 432 [M]+. Found, %: C 72.04; H 6.47; N 6.50.
C26H28N2O4. Calculated, %: C 72.20; H 6.53; N 6.48.
M 432.52.
Compounds Vb–Ve were synthesized in a similar
way.
4-[(3S,3aR,6R,7E)-2,6-Dimethyl-7-(4-propionyl-
oxybenzylidene)-3,3a,4,5,6,7-hexahydro-2H-inda-
1
592, 563 br. H NMR spectrum (DMSO-d6), δ, ppm:
1.22 d (3H, CH3), 1.33 t (6H, CH3), 1.63 m (2H, 5-H),
2.60 s (3H, NCH3), 2.71 m (1H, 3-H), 3.20 m (1H,
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 46 No. 8 2010

ABAKUMOV et al.
1212
zol-3-yl]phenyl propionate (Vb). Yield 80 mg (50%),
mp 154°C, [α]D = –621.91°. IR spectrum, ν, cm–1:
3483, 3282, 2929, 2854, 2119, 1751, 1504, 1448,
1357, 1205, 1162. 1H NMR spectrum (CDCl3), δ, ppm:
1.39 m (8H, CH2), 1.64–1.87 m (4H, 4-H, 5-H),
1.76 m (4H, CH2), 2.55 m (4H, CH2), 2.79 s (3H,
NCH3), 2.80 m (1H, 3a-H), 3.26 m (1H, 6-H), 3.63 d
3
(1H, 3-H, J = 14.1 Hz), 6.99 s (1H, CH=C), 7.06 d
3
3
3
1.27 m (6H, CH3), 1.29 d (3H, CH3, J = 7.1 Hz),
(2H, Harom, J = 8.5 Hz), 7.08 d (2H, Harom, J =
3
1.64–1.88 m (4H, 4-H, 5-H), 2.59 m (4H, CH2), 2.79 s
(3H, NCH3), 2.80 m (1H, 3a-H), 3.26 m (1H, 6-H),
8.5 Hz), 7.35 d (2H, Harom, J = 8.5 Hz), 7.43 d (2H,
H
arom, 3J = 8.5 Hz). Found, %: C 75.18; H 8.21; N 5.20.
3
3.63 d (1H, 3-H, J = 14.0 Hz), 6.99 s (1H, CH=C),
C34H44N2O4. Calculated, %: C 74.97; H 8.14; N 5.14.
3
7.07 d (2H, Harom, J = 8.5 Hz), 7.09 d (2H, Harom
,
4-{(3S,3aR,6R,7E)-7-[4-(4-methoxybenzoyl)-
benzylidene]-2,6-dimethyl-3,3a,4,5,6,7-hexahydro-
2H-indazol-3-yl]phenyl 4-methoxybenzoate (Vf).
Compound IIIa, 0.40 mmol, was dispersed in 5 ml of
anhydrous THF, 45 mg (0.37 mmol) of 4-dimethyl-
aminopyridine was added, 0.38 g (2.40 mmol) of
p-methoxybenzoic acid was then added, the mixture
was cooled to 0°C (ice bath), and 0.50 g (2.40 mmol)
of N,N′-dicyclohexylcarbodiimide was added. The
mixture was stirred for 7 days and was treated as
described above. Yield 50 mg (24%), mp 150–151°C
(from DMF). IR spectrum, ν, cm–1: 2927, 2837, 1728,
3J = 8.5 Hz), 7.35 d (2H, Harom, J = 8.5 Hz), 7.44 d
3
3
(2H, Harom, J = 8.5 Hz). Found, %: C 73.23; H 7.08;
N 6.01. C28H32N2O4. Calculated, %: C 73.02; H 7.00;
N 6.08.
4-[(3S,3aR,6R,7E)-7-(4-Butanoyloxybenzylidene)-
2,6-dimethyl-3,3a,4,5,6,7-hexahydro-2H-indazol-
3-yl]phenyl butanoate (Vc). Yield 70 mg (42%),
mp 141–142°C, [α]D = –615.15°. IR spectrum, ν, cm–1:
2927, 2860, 1758, 1506, 1446, 1363, 1201, 1135.
1H NMR spectrum (CDCl3), δ, ppm: 1.05 m (6H,
CH3), 1.29 d (3H, CH3, 3J = 7.2 Hz), 1.64–1.88 m (4H,
4-H, 5-H), 1.79 m (4H, CH2), 2.54 m (4H, CH2), 2.79 s
(3H, NCH3), 2.80 m (1H, 3a-H), 3.26 m (1H, 6-H),
1
1604, 1512, 1255, 1203, 1162. H NMR spectrum
(CDCl3), δ, ppm: 1.32 d (3H, CH3, 3J = 7.1 Hz), 1.67–
3
1.91 m (4H, 4-H, 5-H), 2.83 s (3H, NCH3), 2.85 m
3.63 d (1H, 3-H, J = 14.1 Hz), 6.99 s (1H, CH=C),
3
3
(1H, 3a-H), 3.30 m (1H, 6-H), 3.67 d (1H, 3-H, J =
7.06 d (2H, Harom), 7.06 d (2H, Harom, J = 8.5 Hz),
7.08 d (2H, Harom, 3J = 8.5 Hz), 7.35 d (2H, Harom, 3J =
13.9 Hz), 3.90 s (6H, OCH3), 6.99 m (4H, Harom),
3
7.03 s (1H, CH=C), 7.19 d (2H, Harom, J = 8.6 Hz),
3
8.5 Hz), 7.44 d (2H, Harom, J = 8.5 Hz). Found, %:
7.22 d (2H, Harom, 3J = 8.6 Hz), 7.41 d (2H, Harom, 3J =
C 73.42; H 7.36; N 5.64. C30H36N2O4. Calculated, %:
C 73.74; H 7.43; N 5.73.
3
8.5 Hz), 7.49 d (2H, Harom, J = 8.5 Hz), 8.16 d (4H,
Harom, 3J = 8.8 Hz). Found, %: C 73.89; H 5.82; N 4.51.
4-[(3S,3aR,6R,7E)-2,6-Dimethyl-7-(4-pentanoyl-
oxybenzylidene)-3,3a,4,5,6,7-hexahydro-2H-inda-
zol-3-yl]phenyl pentanoate (Vd). Yield 50 mg (39%),
mp 125–126°C, [α]D = –553.46°. IR spectrum, ν, cm–1:
3465, 2927, 2856, 1745, 1504, 1446, 1201, 1141.
1H NMR spectrum (CDCl3), δ, ppm: 0.97 m (6H,
C38H36N2O6. Calculated, %: C 74.01; H 5.88; N 4.54.
The authors thank leading engineer I.V. Knyazeva
for her help in measuring mass spectra of some com-
pounds.
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3
CH3), 1.29 d (3H, CH3, J = 7.2 Hz), 1.45 m (4H,
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3
2. Kozachenko, A., Sorokin, V., Kolomzarov, Yu., Nazaren-
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3
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