FLAVOUR AND FRAGRANCE JOURNAL, VOL.

1, 121-124 (1986)

Isolation of Optically Pure (-)-Linalyl Acetate from Clary Sage,

Salvia dorninica L., Lavender and Lavandin
Uzi Ravid, Eli Putievsky and Michal Bassat
Department of Medicinal, Spice and Aromatic Plants, Agricultural Research Organization, Newe- Ya'ar, Post Haifa 31-999, Israel

Raphael Ikan and Vera Weinstein

Department of Organic Chemistry, Natural Products Laboratory, Hebrew University ofJerusalem, Jerusalem 91 -904, Israel

Optically pure (-)-linalyl acetate was isolated from the essential oils of the plants clary sage, Salvia dominica L.,
lavender and lavandin belonging to the Labiatae family. 'H-NMR of synthetic racemic and natural (-)-linalyl
acetate in the presence of various molar ratios of a chiral lanthanide shift reagent Eu(hfc)3 was performed.

KEY WORDS (-)-Linalyl acetate Clary sage Salviu dominica L., Lavender Lavandin 'H-NMR Chiral
Eu(hfc)3.

INTRODUCTION EXPERIMENTAL

Linalyl acetate (3,7-dimethylocta-l,6-dien-3-y1 Clary sage (Salvia scfarea L.), Salvia dominica L.,
acetate) is the principal constituent of the essen- lavender (Lavandula angustifolia Mill.) and
tial oils of bergamot, clary sage, lavender and lavandin (hybrid of L. angustifolia Mill. and L.
lavandin. It is also present in the essential oils of futifofia Vill.), were grown in an experimental
Salvia oficinafis, petitgrain, sassafras, neroli, field at the Newe-Ya'ar Agricultural Experiment
lemon, Italian lime, jasmine, Thymus mastichina, Station. Seeds of a commercial variety of S.
Tagetes patula, Citrus aurantifolia from India, a scfarea (Russian type) received from England,
few Mentha species and others.'** were sown in the autumn of 1982. Seeds of S.
McCreary and co-workers3 and Goering and dominica were collected from several wild popu-
co-workers4 reported the first use of chiral lanth- lations in northern Israel and transferred to the
anide shift reagents with 'H-NMR spectrometry Newe-Ya'ar experimental field. A voucher
to determine the enantiomeric composition of the specimen is retained at Newe-Ya'ar. Commercial
monoterpenes camphor, menthol and menthyl varieties of lavender and lavandin were received
acetate. Plummer and co-workers' determined from a nursery in southern France. The fresh
the enantiomeric purity of several pheromones, mature inflorescences of the four species were
including the monoterpene alcohols trans- steam-distilled for one hour in a 130-L direct
verbenol and ipsdienol, using a chiral shift reag- steam pilot plant apparatus. The isolated oils
ent. The enantiomeric composition of (+)- were dried over anhydrous sodium sulphate and
linalool from the oil of coriander, and of (-)- stored at 4-6°C. Linalyl acetate was isolated from
linalool from the oil of sweet basil, was deter- the oils by fractional distillation in a Perkin-Elmer
mined by 'H-NMR spectrometry using a chiral model 131T microstill at 0.2-0.4mbar. Further
Eu(hfc)+' We report here the isolation and purification was achieved b flash chromatogra-
determination of optically pure (-)-linalyl ace- phy under pressure (2atm.)Y on silica gel Davisil
tate from four Labiatae species using a chiral 60-& 200-425 mesh (Aldrich Chemical Co.),
lanthanide shift reagent. eluant: 1 to 5 per cent solution of ethyl acetate in

0882-5734/86/030121-04$05.00 Received 30 May IY86

0 1986 by John Wiley & Sons. Ltd. Accepted I8 August I986
122 U. RAVID E T A L .

petroleum ether, b.p. 6 0 4 0 ° C . The chemical

purities of natural and synthetic samples of linalyl
acetate were established using a Varian 3700 gas
chromatograph equipped with FID, and a
Hewlett-Packard 3390A integrator. Samples of
0.1 p1 of the natural fractions and of synthetic
linalyl acetate were injected on to a packed glass
column (3 m x 4 mm i.d.) with 5% Carbowax
20M on acid-washed, silanized Chromosorb W
(80-100 mesh) and on to a fused silica capillary
column (25 m) coated with Carbowax 20M.
Operating conditions were: temperature pro-
gramme, 70-190°C (5°C min-'); carrier gas,
nitrogen, 30 and 5 ml min-', respectively, A
synthetic sample of racemic linalyl acetate was
obtained from Carl Roth and Co. Tris[ 3-(hepta-
fluoro-propylhydroxy-methylene)-(+)-camphor-
ato], europium(II1) derivative [ Eu(hfc),], was
obtained from the Aldrich Chemical Co. Optical
rotations were measured on a Perkin-Elmer Model
531 polarimeter. The specific rotation of linalyl
acetate (95% chemically pure) isolated from clary
sage was -8.11" (c = 2.59, EtOH) and of linalyl
acetate (93% chemically pure) from lavender was
-7.43" (c = 2.13 EtOH) (Lit. -7.42" to
-8.18"'*2). 'H-NMR spectra were obtained at
200 MHz with a Bruker Model WP-2OOSY
Fourier transform spectrometer. Linalyl acetate
(10 pl) was dissolved in a solution of 2% TMS in
deuterochloroform (350 p l ) in the NMR tube.
Ten-milligram aliquots of Eu(hfc)3 were added
and dissolved in the solution. Molar ratios of the
lanthanide shift reagent to substrate ([ L]/[S])
A
were 0.15, 0.30, 0.45, and 0.60.

RESULTS AND DISCUSSION

(4
Linalvl acetate is a maior constituent in the essen-
tial oils of the fresh inflorescences from clary sage
(60.2%),' S. dominica (28.4%),8 lavender
(34.9%) and lavandin (26.4%). Various
concentrations of linalyl acetate were found in the
oils from the calyx, corolla, bract and true leaves
of clary sage and S. dominica .' (-)-(3R)-Linalyl
acetate was synthesized from chiral 2,2,4- p p m 8 7 6 5 4 3
trimethyl-l,2-dioxolan-4-carbaldehyde to con-
firm its absolute configuration."'
Eu(hfc), in the presence of ( -)-linalyl acetate Figure 1. 'H-NMR spectra of (-)-linalyl acetate isolated
from clary sage in the presence of Eu(hfc)3 at the molar ratios:
isolated from the essential oils of sage (a) 0.15, (b) 0.60. and (c) spectrum of (-)-linalyi acetate
(Figure 11, S- dominicay 1aveJ'lder and lavandin, at spiked with racemic in the presence of Eu(hfc), at
increasing lanthanide-to-substrate molar ratios [L]/[S] = 0.5s
 (-)-LINALYL ACETATE IN T H E LABIATAE 123

([L])/[S] = 0.15 to 0.60), causes downfield shifts

of the protons of the substrate. The doublet of the
olefinic protons observed at 5.17 ppm in the
unshifted spectrum, moves downfield to 6.27 ppm
at a lanthanide-to-substrate ratio of 0.60. The
singlet of the acetate protons (2.00 ppm in the
unshifted spectrum) shows a downfall signal at
4.67 ppm at [L]/[S] = 0.60. There is no separa-
tion of enantiomeric proton signals at
[L]/[S] = 0.15 to 0.60, so the (-)-linalyl acetate
isolated from the four oils is optically pure.
The spectra of synthetic racemic linalyl acetate
in the presence of E ~ ( h f c )at~ about the same
[ L]/[ S] molar ratios show that the enantiomeric
composition is 50:50 (Figure 2). The absorption
of the olefinic protons is split into two equal sets
of doublets at [L]/[S] = 0.15 to 0.45, and the
absorption of the acetate protons is split into two
signals with a significant enantiomeric shift differ-
ence, AAd = 0.08, at [L]/[S] = 0.60. A t a
lanthanide-to-substrate ratio of 0.30 and 0.45, the
enantiomeric proton signals of the acetate gave
lower AAd values (0.04 and 0.06 ppm, respec-
tively).
Barner and Hiibscher" reported that the enan-
tiomeric shift differences for tert-methyl and
acetyl protons of (RS -1inalyl acetate was
0.05 ppm. It was found" that the E ~ ( h f c )to~
linalool molar ratio of 0.6 is optimal. Spiking of 9
parts of natural (-)-enantiomer with 1 part of
synthetic racemic linalyl acetate at [L]/[S] = 0.55
(Figure l(c)) shows that the absorption of the
olefinic protons at the lower field is that of the
(+)-enantiomer with a 10%enantiomeric excess.
The absorption of the acetate protons of the
(+)-enantiomer is in a higher field compared with
that of the (-)-enantiomer with 10% enan-
tiomeric excess.
Although alcohols interact strongly with chiral
lanthanide shift reagents596and give larger induced
shifts (As) than the other oxygen functions, it is
useful to convert them to their acetate^.^. The
binding site of the acetate ( e 0 ) is different
from that of the alcohol (OH) and produces dif-
ferent shifts upon the addition of chiral
Eu(hfc)3.1ZThe singlet methyl resonance of the
acetate in the 'H-NMR spectra of linalyl acetate is
more helpful than the other resolved resonances
in determining the enantiomeric purity.
We believe that the 'H-NMR 'polarirnetry' is a ppms 0 7 6 5 4
fast, accurate and nondestructive technique for
determining the enantiomeric composition of Figure 2. 'H-NMR spectra of synthetic racemic linalyl acetate
chiral oxygenated terpenes which are present in in the presence of Eu(hfc)3 at the molar ratios: (a) 0.15, and
small quantities in various essential oils. (b) 0.60.
124 U. RAVID E T AL.
Acknowledgements-Contribution from the Agricultural
Research Organisation, The Volcani Centre, Bet Dagan,
Israel. No. 1648-E. 1986 series.
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