FLAVOUR AND FRAGRANCE JOURNAL, VOL. 2, 95-97 (1987)
Isolation and Determination of Optically Pure Carvone Enantiomers from Caraway (Carum carvi L.), Dill (Anethum
graveolens L.), Spearmint (Mentha spicata L.) and Mentha
longifolia (L.) Huds.
Uzi Ravid, Michal Bassat and Eli Putievsky
Department of Medicinal. Spice and Aromatic Plants, Agricultural Research Organization. Newe Ya'ar. Haifa Post 31-999, Israel
Vera Weinstein and Raphael Ikan
Department of Organic Chemistry, Natural Products Laboratory, Hebrew University of Jerusalem, Jerusalem 91-904, Israel
Optically pure (S)-( +)-carvone was isolated from the essential oils of the fruits of caraway and dill. Optically pure
(R)-(-)-carvone was isolated from the essential oils of the leaves of spearmint and Menfha longifolia.
Determination of the enantiomeric purity of the natural flavour was performed by 'H-NMR spectroscopy using a
chiral lanthanide shift reagent, Eu(hfc)3.
KEY WORDS
(S)-( +)-Carvone (R)-(-)-Carvone Carum carvi L. Anelhum graveolens L. Mentha spicata
L. Mentha longifolia (L.) Huds. 'H-NMR Chiral Eu(hfc)3.
INTRODUCTION
EXPERIMENTAL
[(2-methylJ-(l-methylethenyl)-2-cycloCarvone
hexene-1-one] occurs in nature in the (S)( + ) , ( R ) - ( - 1 and (RS) forms. (R)-(-)-Carvone is
a major component of spearmint and kuromoji
oils and is synthesized commercially from ( R ) (+)-limonene. It has been found in Menrha
spicata, M . viridis var. crispa, M . longifolia,
Eucalyptus globulus and several other mint
species. .'
(S)-(+)-carvone is a major component in
caraway and dill oils. It has been also detected in
Anethum sowa, Lippia carviodora, Mentha arvensis and others.'.* It has been found that ( R ) - ( - ) carvone, which has a spearmint odour, is detectable at a lower threshold than its enantiomer,
which has a caraway odour.%' The (RS) form is
present in gingergrass, Listea guatemafeusis,
lavender and Artemisia ferganensis.'.* (S)-(+)Carvone is the starting material for the synthesis
of (R ,Z)-3-met hy l-6-isopropen yl-3,Pdecadien- 1yl acetate, a pheromone component of the female
California red scale.' (R)-(-)-Carvone is used as
a starting material in the preparation of
picrotoxinin.'
Caraway (Carurn carvi L.), dill (Anethum
graveolens L.), spearmint (Mentha spicata L.) and
M. longifolia (L.) Huds. were grown in an
experimental field at the Newe Ya'ar Agricultural
Experiment Station. Seeds of commercial
varieties of caraway and dill received from
Holland, were sown in the autumn of 1984.
Mentha longifolia was collected in 1984 from a
garden and transferred to the Newe Ya'ar
experimental field. A voucher specimen is retained at Newe Ya'ar. A commercial variety of
M . spicara was received from a nursery in
Rumania in the summer of 1980. The fresh foliage
of the Mentha species was steam-distilled for 1 h
in a 130-L direct steam pilot plant apparatus.
Ripe fruits of caraway and dill were handseparated, ground, and hydrodistilled in a modified Clevenger-type apparatus for 2 h. The
isolated oils (yields: caraway 3.6%, dill 3.8%, M.
spicata 1.0%, M . longifolia 0.7%) were dried
over anhydrous sodium sulphate and stored at
44°C.Carvone was isolated from the oils by flash
chromatography under pressure ( 2 atm.) on silica
gel Davisil 60 A, 200-425 mesh (Aldrich Chemic-
'
0882-5734/87/030095-03$05 .OO
0 1987 by John Wiley & Sons, Ltd.
Received 15 May 1987
96
U . R A V I D , M. R A S S A T . E. PUTIEVSKY, V . WEINSTEIN A N D R . IKAN
al Co.), eluant: 1 to 5% solution of ethyl acetate
in hexane: and by fractional distillation in a
Perkin-Elmer model 131 T microstill at 0.2-0.4
mbar. The chemical purities of natural and
commercial samples of carvone were detected by
a Varian 3700 gas chromatograph equipped with
+
FID, and a Hewlett-Packard 3390A integrator.
Samples of 0.1 pl of the natural fractions and of
commercial carvone were injected on a packed
glass column (3m x 4mm i.d.) with 5%
Carbowax 20M on acid-washed, silanized Chromosorb W (80-100 mesh) and on a fused silica
capillary column (25 m) coated with Carbowax
20M. Operating conditions were: temperature
programme, 7&200"C (5°C min-I); carrier gas,
nitrogen, 30 and S m l min-', respectively. A
commercial sample of (S)-( +)-carvone was
obtained from Carl Roth and Co. ([a]:' + 54.0";
.
c = 5.25, EtOH) and (R)-(-)-cawone
was
PI.
8
7
6
5
4
obtained from R. C. Treatt and Co. ([a];'
-59.1';
c
=
3.50. EtOH). Tris (3- Fig. I . ' H - N M R spectra of (S)-(+)-carvonc
[LI/[S] = 0.7-0.8
(heptafluoropropylhydroxymethy1ene)-( )camphorate], europium ( I l l ) [ E u ( h f ~ ) ~ ]was
,
obtained from Aldrich Chemical Co. Optical
rotations were measured on a Perkin-Elmer
Model 531 polarimeter. 'H-NMR spectra were
obtained at 200MHz with a Bruker Model
WP-2OOSY Fourier transform spectrometer. Carvone (lOpl) w a s dissolved in a solution of 2%
TMS in deuterochloroform (350 pl) in the NMR
tube. Ten-milligram aliquots of Eu(hfc)? were
added and dissolved in the solution. Molar ratios
of the lanthanide shift reagent to substrate
([L]/[S]) were 0.45, 0.60, 0.75, 0.90, 1.05 and
1.20.
.
L
......
-.
2
3
with Eu(hfc)l iit
+
RESULTS AND DISCUSSION
Carvone is the major constituent in the essential
oils of the ripe fruits from caraway (51.2%) and
dill (59.3%). and of the fresh leaves from two
Metirliu species (69.9% in M. spicata and 61.6%
in M. longifoliu). 'H-NMR spectra of the purified
natural ( S ) - (+)-carvone isolated from caraway
and dill. and of the (R)-(-)-cawone isolated from
M. .spicuru and M. lotigifoliu in the presence of
Eu(hfc), at increasing lanthanide-to-substrate
molar ratios ([L]/[S] = 0.45 t o 1.20), show that
there is n o separation of enantiomeric proton
signals, so the carvone from the four oils is
enantiomerically pure (Figures 1.2). The singlet
of the the allylic C-7 methyl protons (1.70 ppm in
v1.8
7
6
.
.
5
.
.
4
.
.
.
3
Fig. 2. ' H - N M R spectra of (R)-(-)-cawone with Eu(hfc),
at
[ L ] I [ S ]= 0.7-0.8
the unshifted spectrum) shows a significant
downfield signal at 6.02 ppm for the (S)-(+)carvone and at 5.97 ppm for the (R)-(-)-cawone,
at [L]/[S] = 1.20. The singlet of the allylic C-10
methyl protons moves downfield to 2.24 ppm at
the same [L]/(S] ratio. The large downfield
changes in the chemical shifts of the two methyl
OPTlCALLY PURE CARVONE ENANTlOMERS
An
I
I
.
~
7
6
5
i,
4
97
phenyl-2-pentanone, using europium chiral shift
reagents of [L]/[S] = 1.O-2.0. were in the range of
0.03
to
0.75."."'
Natural
oxygenated
monoterpenes isolated from essential oils are
enantiomerically ure in the case of (-)-linalol
from sweet basil' and (-)-linalyl acetate from
clary sa e, Salvia dominica, lavender and
lavandin.82 (+)-Linalol from coriander' I and
(+)-terpinen-4-01 from sweet marjoramI3 are
mixtures of the two enantiomers with the
(+)-enantiomer predominant. (R)-(-)-Carvone
is synthesized commercially from readily available (R)-(+)-limonene by nitrosochlorination.
dehydrochlorination and hydrolysis" with retention of the integrity of the chiral centre. Routine
detection of the enantiomeric purity of this
important nature identical flavour by 'H-NMR
using Eu(hfc)3 is a simple, fast and accurate
technique.
3
Fig. 3. 'H-NMR spectra of (RS)-carvone with Eu(hfc), at
[L]/[S] = 0.7-0.8
protons are due to the fact that the C-7 methyl is
much closer to the binding site of the ketone
(C=O) to the europium chelating agent than is
the C-10 methyl. The (S)-(+)-carvone was spiked
with the (R)-(-)-enantiomer in a ratio of 1:1, in
the presence of Eu(hfc)3 (Figure 3) at [L]/[S] =
0.45 to 1.20. The absorption of the C-7 methyl
protons is split into two equal signals at [L]/[S] =
0.45 (AAd = 0.01) to [L]/[S] = 1.20 ( A A b =
0.05). There is no splitting of the absorption of
the C-10 methyl protons at the same lanthanideto-substrate molar ratios. Spiking of the two
enantiomers in a 1:2 ratio shows that the
absorption of the C-7 methyl protons at the
higher field is that of the (R)-(-)-enantiomer.
Spiking eliminates errors due to changes in the
[L]/[S] ratio, the temperature, and other factors
controlling the downfield position of the singlet
by showin
both enantiomers with one
enhanced.' 'H-NMR spectra of commercial samples of ( S ) - ( + ) - and (R)-(-)-cawone, in the
presence of Eu(hfc)z at molar ratios of 0.45 to
1.20, show that the samples were enantiomerically pure.
The magnitudes of the enaiitiomeric shift
differences of the methyl protons of the ketones
camphor, 3-methyl-2-pentanone and 3-methyl-3-
Acknorc~/e~~ernieirr-Contribution
from the Agricultural Research organization. The Volcani Center, Bet Dagan. Israel.
No. 2052-E. 1987 series.
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