Synthesis and properties of benzylidene derivatives of terpenoid ketones

Article abstract of DOI:10.1023/A:1015505414760

Optically active benzylidene derivatives of camphor and menthone were obtained in preparative yields by condensation of the ketones with aromatic aldehydes in DMSO in the presence of t-BuOLi. The synthesized α,β-unsaturated ketones show high specific rotation and thus are suitable to bedoping component to liquid-crystalline compositions.

Full text of DOI:10.1023/A:1015505414760

Russian Journal of Organic Chemistry, Vol. 38, No. 2, 2002, pp. 196 199. Translated from Zhurnal Organicheskoi Khimii, Vol. 38, No. 2, 2002,
pp. 215 218.
Original Russian Text Copyright
2002 by Chuiko, Vinarskaya, Izotova, Tychinskaya.
Synthesis and Properties of Benzylidene Derivatives
of Terpenoid Ketones
V. A. Chuiko, Zh. V. Vinarskaya, L. V. Izotova, and L. Yu. Tychinskaya
Institute of Physical Organic Chemistry, National Academy of Sciences of Belarus, Minsk, 220072 Belarus
Received March 15, 2001
Abstract Optically active benzylidene derivatives of camphor and menthone were obtained in preparative
yields by condensation of the ketones with aromatic aldehydes in DMSO in the presence of t-BuOLi. The
synthesized , -unsaturated ketones show high specific rotation and thus are suitable to bedoping
component to liquid-crystalline compositions.
In the chemistry and physics of mesomorphic
systems, nematic liquid crystals doped with optically
active organic compounds attract special interest.
The specific feature of these system lies in
their spiral hypomolecular structure analogous to the
cholesterol mesophase. This behavior is associated
with the capability of the optically active compounds
to induce ordering into helix in the nematic phase.
Chiral , -unsaturated ketones prepared by crotonic
condensation from l-menthone and aromatic
aldehydes exhibited such activity [1].
refining the synthetic procedure 2-cyclohexylcyclo
hexanone (III) was used.
To the synthesis of benzylidene derivatives we
applied bezaldehyde (IV), anisaldehyde (4-methoxy-
benzaldehyde) (V), and 4-phenylbenzaldehyde (VI).
Since the crotonic condensation does not affect the
asymmetrical atom in camphor (II) and at least one
of the asymmetrical centers in menthone (I) molecule
we believed that the derivatives synthesized would
also be optically active. Although the aromatic
aldehydes are more reactive than aliphatic ones, they
virtually cannot be brought into crotonic condensation
under the standard conditions of the reaction (with
alkali as catalyst and ethanol as solvent). In a patent
[2] the condensation was described of ketone II with
tetramethylterephthalaldehyde performed by boiling
in anhydrous toluene with sodium hydroxide for 96 h;
the yield was 38%. The yields of the same order of
magnitude (30 50%) were attained by condensation
of ketone I with aldehydes IV and V in the presence
of potassium hydroxide in polar aprotic solvents:
DMF, DMSO, HMPA, and dimethylacetamide [3].
The yield of condensation products with ketones II
and III under these conditions was low. Potassium
and sodium ethylates turned out to be inefficient
catalysts in condensation carried out in anhydrous
ethanol. The use of t-BuOK in DMSO resulted in
30 60% yields.
The goal of this study was to develop of a more
efficient preparation procedure for menthone (I)
derivatives, and synthesis of optically active benz-
ylidene derivatives of camphor (II). As a model for
Organolithium compounds are known to be applied
as basic catalysts. Camphor condensation with trans-
4-(4-methylphenyl)-3-buten-2-one in the presence of
BuLi occurs at 78 C to afford the condensation
product in hardly 7% yield [7]. We attempted to use
tBuOLi as catalyst. The use of lithium as counterion
with a large solvate radius leaves room for better
results. The experimental data are presented in a
table.
R = H (IV), OCH3 (V), Ph (VI); VII, X, R = H (a),
OCH3 (b), Ph (c).
1070-4280/01/3802-196$27.00 2002 MAIK Nauka/Interperiodica

SYNTHESIS AND PROPERTIES OF BENZYLIDENE DERIVATIVES
197
Yields and characteristics of condensation products of ketones I III with aromatic aldehydes IV VI
Initial
ketone no.
Reaction
time, min
[ ]2D0
(c, solvent)
Aldehyde no.
Yield, %
mp,
C
I
IV
V
VI
IV
V
VI
IV
V
60
60
75
60
40
30
45
40
60
62
83
78
70
85
82
67
88
85
217 (2.6, chloroform)
253 (4.3, acetone)
274 (1.7 chloroform)
+361 (2.7, acetone)
+498 (3.2, acetone)
+476 (2.3, chloroform)
115 117
105
92 94
128
II
III
160
102
113
137
VI
The use of t-BuOLi instead of potassium hydroxide
did not significantly affect the yield of 2-benzylidene-
menthone (VIIa), but the reaction time notably
reduced (1 h against 4 h by procedure [3]). Reaction
with the other aldehydes provided higher yields.
that crotonic condensation undergoes only one
epimer, namely (+)-isomenthone [7], but the reasons
of this selectivity have not been explained. This
statement seems dubious: hardly the spatial orienta-
tion of the methyl group would affect the formation
of enolate ion by proton abstraction from the C4 of
the six-membered menthone ring; it is also unlikely
that the reactivity of the epimeric enolate-ions would
be influenced. The difference in the total energy of
ions A and B originating respectively from ketones I
and VIII calculated in the MM2 approximation equals
2-(4-methoxybenzylidene)menthone
(VIIb)
was
obtained in 83% yield, and 2-(4-phenylbenzylidene)-
menthone (VIIc) in 78% yield.
Under conditions of crotonic condensation of
aromatic aldehydes with trans-3-menthone (I) arise
benzylidene derivatives of cis-3-menthone, iso-
menthone (VIII). The formation of ketone VIII
derivatives from the initial ketone I was not un-
expected. In the basic medium trans-isomer I is in
equilibrium with cis-isomer VIII due to keto-enol
tautomerism. We checked it experimentally. As
showed the GLC of the reaction mixture before
visible crystallization both ketones I and VIII were
present therein in the ratio 70: 30 in agreement with
the data from [5]. It is also seen from the changed
optical activity of ketones: the optical activity of the
initial menthone was [ ]2D0 27.8 , and that of the
equilibrium mixture was [ ]2D0 +8.5 . The specific
rotation of ketone VIII calculated by Biot law amounts
to +92 in agreement with the known data [5, 6].
1
only to 1.4 kcal mol , and thus the conformational
transitions are quite probable.
We believe that more logical is an assumption of
epimerization of the arising , -unsaturated ketones
However the lack of menthone I derivatives among
the reaction products was unexpected. It is believed
R = H (a), OCH3 (b), Ph (c).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 2 2002

198
CHUIKO et al.
(IX). The geometry optimization for ions originating
from ketones IX during enolization at C4 atom shows
that in both cases forms the same ion C. The proton
addition causing minimum changes in the orientation
of the substituents and resulting in the low-energy
conformation of the six-membered ring should afford
benzylidene derivatives of isomenthone VIIa c.
inert, and the attempts to prepare by standard proce-
dures from the derivatives of ketones I III epoxides,
oximes, and Schiff bases have been unsuccessful.
EXPERIMENTAL
GLC analysis of reaction mixtures and condensa-
tion products was carried out on chromatograph
Chrom-4 equipped with flame-ionization detector,
carrier gas nitrogen, flow rate 40 ml/min, column
1500 3 mm, stationary phase 5% XE-60 on Inerton
AW-DMCS (0.2- 0.25 mm), oven temperature
programmed from 70 to 260 C at a rate 5 deg/min.
1H NMR spectra were registered on spectrometer
Tesla BS-567A in CDCl3 and C6D6, internal refer-
ence HMDS.
Initial ketone I, [ ]20 27.8 , was obtained by
oxidation of the naturalDmenthol. The derivatives of
ketone II were prepared from natural Japanese
camphor, [ ]2D0 +46.6 (c 5.7, ethanol).
The hypothetical ion D with a pseudoequatorial
methyl group that may lead to menthone derivatives
IXa c is more strained than ion C because the methyl
group adjacent to the aromatic ring should cause
distortion of coplanarity in the double bonds system.
The torsional angle C(O )C=CPh for ions Da c
equals to 10.4, 10.1, and 9.9 respectively whereas
for ions Ca c it is 2.8, 2.7. and 2.8 . The calculated
energy difference for the corresponding pairs of ions
1
Da c and Ca c is 6.61, 6.33, and 6.63 kcal mol .
Thus the conformational transition C D is a lot less
probable than A B transition.
The developed condensation procedure turned out
to be efficient also for preparation of optically active
benzylidene derivatives of d-camphor. Under the
described conditions the reaction with camphor occurs
even readier than with menthone. In condensation of
ketone II with aldehyde VI already several minutes
after the mixing of reagents the crystalline reac-
tion product starts to precipitate. Somewhat slower
are reactions with aldehydes IV and V (see table).
Condensation of ketones I III with aromatic
aldehydes. In 15 ml of anhydrous DMSO were dis-
solved 3 g (0.02 mol) of ketone and 0.022 mol of
aldehyde. To a mixture of 1.2 g (0.015 mol) of t-BuLi
and 10 ml of anhydrous DMSO was added dropwise
the solution of reagents controlling the rate of addi-
tion so as the temperature of the reaction mixture did
not exceed 20 C; the reaction mixture was cooled
with water bath. The stirring was continued till
complete consumption of the ketone. Then the reac-
tion mixture was poured into 250 ml of ice water
containing 10 ml of acetic acid. The precipitate was
filtered off, washed with water, and recrystallized
from ethanol.
1
As show H NMR data, the cinnamoyl fragment
in the obtained derivatives of ketone II possesses
E-configuration as also in the respective derivatives of
ketone I. To the olefin proton of these compounds
corresponds the signal in the region 7.17 7.23 ppm;
this value for a proton of a cinnamoyl fragment in a
Z-configuration should be 6.3 ppm [8]. The same
conclusion follows from the geometry optimization
for these compounds in the MM2 approximation.
1H NMR spectra of compounds VIIa c were
consistent with the published data [7].
1
3-Benzylidenecamphor (Xa). H NMR spectrum,
, ppm: 0.83 s (3H, CH3), 1.00 s and 1.03 s [6H,
(CH3)2C], 1.40 2.32 m (4H, 2CH2), 3.11 d (1H,
HC, J 4 Hz), 7.23 s (1H, =CH), 7.25 7.51 m
(5H arom).
Note however that noncoplanarity of the
C(O)C=CPh fragment in the derivatives of ketone II
is considerably less than in derivatives of ketone I. If
in the latter the torsion angle reaches 57 59 , in the
molecules f camphor derivatives this value is only
3 4 . The , -unsaturated ketones obtained possess
extremely high optical activity, apparently due to
diastereomeric homogeneity. Thus they are promising
as chiral doping components for liquid-crystal
compositions.
3-(4-Methoxybenzylidene)camphor (Xb).
1H NMR spectrum, , ppm: 0.78 s (3H, CH3),
0.98 s and 1.00 s [6H, (CH3)2C], 1.46 2.28 m
(4H, 2CH2), 3.08 d (1H, HC, J 5 Hz), 7.17 s (1H,
=CH), 6.92 d and 7.42 d (4H arom, J 9 Hz).
1
3-(4-Phenylbenzylidene)camphor (Xc). HNMR
The synthesized derivatives of ketones I III are
well soluble in acetone, ether, chloroform, somewhat
less in alcohol, and therefore this solvent is suitable
for recrystallization. They are relatively chemically
spectrum, , ppm: 0.80s (3H, CH3), 0.96s and 1.00 s
[6H, (CH3)2C], 1.44 2.23 m (4H, 2CH2), 3.16 d (1H,
HC, J 7 Hz), 7.23 s (1H, =CH), 7.08 7.66 m (5H
arom).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 38 No. 2 2002

SYNTHESIS AND PROPERTIES OF BENZYLIDENE DERIVATIVES
199
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