Unsaturated hydrocarbons with fruity and floral odors

Article abstract of DOI:10.1021/jf991156p

Hydrocarbons usually do not exhibit odors of interest or well-defined character. However, certain cyclic alkenes have been associated with typical and pleasant notes, such as fruity, green, and floral. One of the best known examples is represented by the

Full text of DOI:10.1021/jf991156p

J. Agric. Food Chem. 2000, 48, 1285−1289
1285
Un sa tu r a ted Hyd r oca r bon s w ith F r u ity a n d F lor a l Od or s
Cecilia Anselmi,†,‡ Marisanna Centini,†,‡ Paola Fedeli,† Maria Laura Paoli,† Alessandro Sega,†,‡
Carla Scesa,‡ and Paolo Pelosi*,§
Istituto di Chimica Organica, University of Siena, Italy, Scuola di Specializzazione in Scienza e Tecnologia
Cosmetiche, University of Siena, Italy, and Dipartimento di Chimica e Biotecnologie Agrarie,
University of Pisa, Italy
Hydrocarbons usually do not exhibit odors of interest or well-defined character. However, certain
cyclic alkenes have been associated with typical and pleasant notes, such as fruity, green, and floral.
One of the best known examples is represented by the isomeric megastigmatrienes, endowed with
a pleasant smell of tropical fruits. From the structures of these odorants, 24 analogues and
homologues, most of them cyclic alkenes, but including also some open-chain alkenes, have been
synthesized to define structural parameters related to the characteristic odors of these compounds.
The number and position of double bonds, the substitution on the ring, and the size of the ring are
the variables taken into account. Most of the new compounds present a mainly fruity character,
associated in several cases with floral and green notes, producing an overall sensation described as
“tropical fruit”.
Keyw or d s: Olfaction; hydrocarbons; structure/ odor relationships; fruity odor; Wittig reaction
INTRODUCTION
saturated hydrocarbon has no preferential orientation
when interacting with olfactory receptor proteins and
therefore can equally fit into different types of receptors;
the result is likely to be similar for most volatile
hydrocarbons and difficult to describe with specific
terms. An exception to this rule is provided by hydro-
carbons of medium size (8-12 carbon atoms) and round
shape: these compounds present odors of camphor/
balsamic/turpentine, typical of other compounds of
similar size and shape, such as camphor and eucalyptol
(Amoore, 1967; Pelosi and Pisanelli, 1981). In these
odorants, the position of the functional group on the
molecule is of little consequence, given their round
shape, and therefore neither is its presence.
With this single exception, we have no record of
saturated hydrocarbons endowed with specific and
characteristic odors. However, in another chemorecep-
tion system, the perception of pheromones in insects,
there are interesting examples of such phenomena.
Several Diptera and Hymenoptera species utilize cu-
ticular hydrocarbons as sex pheromones. Usually they
are molecules of very long chains, up to 37 carbon atoms,
with little branching (Carlson et al., 1998). These are
molecules of negligible volatility and are perceived by
direct physical contact. The lack of any functional group,
which could represent a stronger site of binding in the
molecule, does not indicate a preferential orientation of
the pheromone when interacting with its receptor
protein. On the other hand, such specificity does exist,
as shown by the specific behavioral responses; conse-
quently, there should be a very close fitting between
ligand and protein, as the van der Waals forces, the only
ones present in hydrocarbons, decrease very rapidly
with distance.
Predicting the odor of a molecule on the basis of its
chemical structure is a problem still far from being
solved in general terms. However, the enormous wealth
of data available in the literature on the odors of pure
compounds provides indications and guidelines for ap-
proaching this problem in a systematic way, at least for
some classes of odorants (Beets, 1978; Theimer, 1982;
Muller and Lamparski, 1994; Rossiter, 1996).
In most cases, the odor of a molecule can be related
to its “oriented profile”, that is, to its shape observed
from the functional group. This part of the molecule, in
fact, is likely to establish a relatively strong interaction
(a hydrogen bond or a dipole-dipole interaction) with
the core of the receptor protein and therefore make the
fitting of the molecule into the receptor site more
specific. After the discovery of olfactory receptors (Buck
and Axel, 1991) and their functional expression (Zhao
et al., 1998), modeling the specific interactions between
odorant and receptor protein is no longer a theory but
has found its experimental ground (Malnic et al., 1999).
Once a certain number of olfactory receptors are func-
tionally expressed and their ligand specificities defined,
a reasonable model for the selective interactions of each
receptor protein with its ligands could be proposed.
So far, the current model of the oriented profile,
proposed for most types of odors, may also explain why
the odor of saturated hydrocarbons is generally de-
scribed as noncharacteristic and difficult to define, a sort
of “gray” odor to make a parallel with colors. In fact, a
* Address correspondence to this author at Dipartimento di
Chimica e Biotecnologie Agrarie, Via S. Michele 4, 56124 Pisa,
Italy (telephone +39/050/571564; fax +39/050/574235; e-mail
ppelosi@agr.unipi.it).
Unlike saturated hydrocarbons, several alkenes are
endowed with strong characteristic odors. Their specific
interactions with olfactory receptors is also supported
by different olfactory notes recorded with the enanti-
omers of some alkenes. Limonene, particularly the R(+)
† Istituto di Chimica Organica.
‡ Scuola di Specializzazione in Scienza e Technologia Cos-
metiche.
§ Dipartimento di Chimica e Biotecnologia Agrarie.
10.1021/jf991156p CCC: $19.00 © 2000 American Chemical Society
Published on Web 03/09/2000

1286 J. Agric. Food Chem., Vol. 48, No. 4, 2000
Anselmi et al.
was checked by gas chromatography on a Perkin-Elmer 8500
apparatus, using a 12 m DB1 apolar capillary column.
Alkene 23 was prepared by reaction of 1,6-dimethylcyclo-
hexanone with butyllithium, followed by dehydration with
sulfuric acid.
enantiomer, is endowed with a citrus odor; its optical
antipode is less citrus and more turpentine (Werkhoff
et al., 1993). The enantiomers of R-phellandrene are also
differently perceived: the S(+) isomer exhibits a dill
note, whereas its enantiomer has a terpene-medicinal
odor (Blank et al., 1991). Other examples of alkenes
endowed with characteristic pleasant odors include
ocimene (green, tropical with floral notes; Ohloff, 1990),
bisabolene (woody, citrus; Ohloff, 1990), â-caryophyllene
(woody, spicy; Arctander, 1969), â-santalene (woody;
Arctander, 1969), and several others. However, com-
pared to other compounds, the odors of alkenes have
not been extensively investigated, probably because of
their high volatility and their susceptibility to oxidation,
which prevent practical uses in the perfumery and
flavoring industries.
Among the best studied are the megastigmatrienes
(2,2,6-trimethyl-1-butenylidenecyclohexene), discovered
in the volatiles of passion fruit and contributing to its
characteristic tropical fruit odor (Whitfield and Sug-
owdz, 1979). They are generally endowed with very
pleasant fruity and floral notes, but the four geometrical
isomers are described with different olfactory terms,
indicating specific interactions of these molecules with
their receptors.
The interest in the olfactory properties of these
compounds and their contribution to the flavor of
passion fruit is also related to their volatility and ease
of oxidation, which may markedly modify the organo-
leptic characteristics of processed or preserved juice.
Most of the studies, however, were aimed at establishing
the structures of the natural compounds and designing
synthetic methods, whereas no systematic investigation
on the relationships between odor and molecular struc-
ture has been performed with this class of compounds.
In this paper we approach the problem of structure-
odor relationships, taking into consideration a defined
group of alkenes, containing a cyclohexane ring and at
least one chain, with one or two unsaturations. These
odorants share with the megastigmatrienes a six-carbon
ring and an unsaturated chain but also bear some
similarities to structures endowed with floral notes,
such as tetrahydropyranyl ethers of cyclohexanols and
phenols (Anselmi et al., 1992, 1993, 1994). Cyclopentane
and cycloheptane homologues, as well as open-chain
alkenes, have also been included in this study.
The structures of individual compounds were established
1
by H and 13C NMR spectroscopy as follows.
1-[(E,Z)-2′Bu ten ylid en e]cycloh exa n e (2): (Z) 1H δ 1.75
(d, 3H, J H3′-H4′ ) 6.8, H 4′), 5.4 (dq, 1H, J H2′-H3′ ) 10.6, J H3′-CH3
) 6.8, H3′), 6.03 (bd, 1H, J H1 -H2 ) 10.4, H1′), 6.3 (m, 1H, H2′,
′
′
J H1′-H2′ ) 10.4, J H2′-H3′ ) 10.6). (E) 1H δ 1.75 (d, 3H, J H3′-H4′
)
6.8, H4′), 5.6 (dq, 1H, J H3′-H2′ ) 14.9, J H3′-H4′ ) 6.8, H3′), 5.7
(bd, 1H, J H1′-H2′ ) 10.7, H1′), 6.3 (m, 1H, J H1′-H2′ ) 10.7, J H2′-H3′
) 14.9, J H2′-H4′ ) 1.4, H2′). (E,Z) 1.55 (bs, 6H, H3, H4, H5), 2.05-
2.4 (m, 4H, H2, H6).
1-[(E,Z)Bu tylid en e]-2-m eth ylcycloh exa n e (3): 1H δ 0.89
(t, 3H, J H4′-H3′ ) 7.2, H4′), 1.04 (d, 3H, J CH3-H2 ) 6.9, CH3-2),
1.35 (m, 2H, J H4′-H3′ ) 7.2, H3′), 1.55-1.85 (m, 4H, H4, H5, H6b),
1.7 (m, 2H, H3), 1.95 (m, 2H, H2′), 2.2 (m, 1H, H2), 2.48 (dt,
1H, J H6a-H6b ) 13.14, H6a), 5.1 (m, 1H, J H1′-H2′ ) 6.9, H1′). 13C
δ 14.0 (CH3), 19.0 (CH3), 23.4 (CH2), 25.8 (CH2), 28.3 (2 × CH2),
29.5 (CH2), 38.7 (C-2), 118.9 (C-1′, E), 121.5 (C-1′, Z), 137.0
(C-1), 143.5 (C-1).
1-[(E,Z,2′E,2′Z)- 2′-Bu ten ylid en e]-2-m eth ylcycloh exa n e
(4): (Z) 1H δ 1.09 (d, 3H, J CH3-H2 ) 6.7, CH3-2), 1.75 (bd, 3H,
J H4′-H3′ ) 6.7, H4′), 5.45 (dq, 1H, J H3′-H2′ ) 9.8, J H3′-H4′ ) 6.7,
H3′), 6.03 (bd, 1H, J H1′-H2′ ) 11.2, H1′), 6.3 (m, 1H, H2′). (E) 1H
δ 1.04 (d, 3H, J CH3-H2 ) 6.9, CH3-2), 1.72 (dd, 3H, J H3′-H4′
)
5.6, H4′), 5.6 (m, 1H, J H3′-H2′ ) 14.7, J ) 5.6, H3′), 5.73
H3′-H4′
(d, 1H, J H2′-H3′ ) 10.7, H1′), 6.35 (m, 1H, J H2′-H3′ ) 14.7, J H2′-H1′
) 10.7, H2′). (E,Z) 2.55-2.75 (m, 2H), 2.05-2.25 (m, 1H), 1.82-
2.05 (m, 2H), 1.6-1.8 (m, 5H), 1.3-1.6 (m, 4H), 1.1-1.3 (m,
2H).
1-[(E,Z)Bu tylid en e]-3-m eth ylcycloh exa n e (7): 1H δ 0.9
(m, 3H, CH3-3), 0.97 (m, 3H, J H4′-H3′ ) 7.0, H4′), 1.1 (m, 1H,
H3), 1.42 (m, 2H, J H3′-H2′ ) 7.0, J H3′-H4′ ) 7.0, H3′, H2b, H6b),
1.75 (m, 4H, H4, H5), 1.95 (q, 2H, J H2′-H3′ ) 7.0, J H2′-H1′ ) 7.0,
H2′), 2.1 (m, 1H, H2a), 2.48 (m, 1H, H6a), 5.11 (m, 1H, H1′). 13C
δ 13.7 (CH3), 22.2 (CH3), 22.4 (CH3), 23.3 (CH2), 26.8 (CH2),-
27.6 (CH2), 28.1 (CH2), 29.2 (CH2), 29.3 (CH2), 33.7 (CH), 34.5
(CH), 35.3 (CH2), 36.7 (CH2), 37.0 (CH2), 46.6 (CH2), 121.6 (C-
1′).
1-[(E ,Z,2′E ,2′Z)-2′-Bu t e n ylid e n e ]-3-m e t h ylcycloh e x-
a n e (8): (Z) 1H δ 0.98 (d, 3H, J HCH
) 6.3), 1.75 (d, 3H,
H
3
J H4′-H3′ ) 6.9), 5.4 (dq, 1H, J H3′-H2′ ) 31-0.4, J H3′-H4′ ) 6.9, H3′),
6.03 (dd, 1H, J H1′-H2′ ) 11.7, J H1′-H2 ) 3.6, H1′), 6.30 (m, 1H,
1
H2′). (E) H δ 0.93 (d, 3H, J HCH
) 6.6, CH3), 1.75 (d, 3H,
H
J H4′-H3′ ) 6.9, H4′), 5.57 (dq, 1H,3J- H3′-H4′ ) 6.9, J H3′-H2′ ) 14.5,
H3′), 5.73 (dd, 1H, J H1′-H2′ ) 11.8, J H1′-H2 ) 3.6, H1′), 6.30 (m,
1H, J H2′-H3′ ) 14.3, J H1′-H2′ ) 3.6, H2′). (E,Z) 2.55-2.75 (m, 2H),
2.05-2.30 (m, 2H), 1.9-2.05 (m, 1H), 1.6-1.9 (m, 5H), 1.2-
1.6 (m, 4H), 1-1.2 (m, 2H).
3
1-Bu tylid en e-4-m eth ylcycloh exa n e (9): 1H δ 0.88 (d, 3H,
J CH3-H4 ) 6.5, CH3), 0.9 (t, 3H, J H3′-H4′ ) 6.5, H4′), 1.35 (m,
2H, H3′), 1.55 (m, 1H, H4′), 1.75 (m, 4H, H3, H5), 1.95 (m, 2H,
H2′), 2.1 (m, 2H, H2, H6), 2.55 (m, 2H, H2, H6), 5.1 (bt, 1H,
J H1′-H2′ ) 7.2, H1′). 13C δ 8.5 (CH3), 16.8 (CH3), 18.0 (CH2), 22.7
(CH2), 24.0 (CH2), 27.7 (C-4), 30.8 (CH2), 31.2 (CH2), 31.7 (CH2),
116.1 (C-1′), 133.9 (C-1).
MATERIALS AND METHODS
NMR Sp ectr a . 1H NMR spectra were recorded on a 60 MHz
Perkin-Elmer R-600 or a 200 MHz Bruker AC-200 in CDCl3.
Chemical shifts (δ) are indicated in parts per million with
reference to tetramethylsilane, used as internal standard.
Coupling constants (J ) are reported in hertz. 13C NMR spectra
and nuclear Overhauser effect (NOE) experiments were run
on a 200 MHz Bruker AC-200 in CDCl3.
Syn th esis of th e Od or a n ts. All of the compounds, except
23, were synthesized through Wittig reaction between propyl-,
2-propenyl-, butyl-, or 2-butenyltriphenylphosphonium bro-
mide and the appropriate ketone. Typically, to 20 mmol of the
triphenylphosphonium salt in 100 mL of diethyl ether was
slowly added an equimolar amount of n-butyllithium in hexane
at 0 °C. After 3 h, the ketone (20 mmol) was added, and the
reaction mixture was stirred for 16-42 h at room temperature
and finally treated with water (50 mL). The ethereal extract
afforded the crude alkene, which was distilled under reduced
pressure. Yields ranged from 25 to 80%. Samples for NMR
spectra and odor evaluation were further purified by column
chromatography on silica gel 60 (Merck 40-60 µm), using a
petroleum ether as the eluent. The purity of the final samples
1-[(E,Z)-2′-Bu ten yliden e]-4-m eth ylcycloh exan e (10): (E)
1H δ 0.92 (d, 3H, J CH
) 6.5, CH3-4), 1.85 (d, 3H, J H4′-H3′ )
H
3-
4
6.6, H4′), 5.6 (dq, 1H, J H3′-H2′ ) 14.9, J H3′-H4′ ) 6.6, H3′), 5.75
(bd, 1H, J H1′-H2′ ) 10.8 H1′), 6.3 (dd, 1H, J H1′-H2′ ) 10.8, J H2′-H3′
1
) 14.9, H2′). (Z) H δ 1.85 (d, 3H, J H4′-H3′ ) 6.6, H4′), 5.43 (m,
1H, J H2′-H3′ ) 10.3, J H3′-H4′ ) 6.6, H3′), 6.07 (bd, 1H, J H1′-H2′
)
11.5, H1′), 6.3 (m, 1H, J H2′-H1′ ) 11.5, J H2′-H3′ ) 10.3, H2′). (Z,E)
2.65-2.85 (m, 2H), 2.0-2.45 (m, 3H), 1.7-2.0 (m, 5H), 1.45-
1.7 (m, 2H), 1.0-1.2 (m, 2H). (E) 13C δ 18.2 (CH3), 21.9 (CH3),
28.3 (CH2), 32.8 (CH), 35.8 (CH2), 36.7 (CH2), 121.9 (CH), 126.5
(CH), 127.4 (CH), 140.1 (C-1). (Z) 13C δ: 13.0 (CH3), 21.9 (CH3),
28.2 (CH2), 32.8 (CH), 36.4 (CH2), 36.9 (CH2), 117.0 (CH), 123.6
(CH), 124.9 (CH), 142.3 (C-1).
1-Bu tylid en e-4-eth ylcycloh exa n e (11): 1H δ: 0.88 (t, 6H,
H
4′, H8), 1.15-1.45 (m, 4H, H3′, H7), 1.63-1.88 (m, 4H, H3, H5),
1.90-2.05 (m, 3H, H2′, H4), 2.15 (m, 2H, H2, H6), 2.57 (m, 2H,

Hydrocarbon Odorants
J. Agric. Food Chem., Vol. 48, No. 4, 2000 1287
1
H2, H6), 5.07 (bt, 1H, H1′, J H1′-H2′ )7.2 Hz). 13C δ 11.6 (CH3),
13.7 (CH3), 23.3 (CH2), 27.9 (CH2), 29.3 (CH2), 29.4 (CH2), 33.7
(CH2), 34.5 (CH2), 36.5 (CH2), 39.7 (C-4), 121.2 (C-1′), 139.6
(C-1).
5-Eth yl-2,4-h ep ta d ien e (20): (E) H δ 5.6 (m, 1H, J H2-H3
) 14.7, J H1-H2 ) 7.3, H2), 5.75 (bd, 1H, J H3-H4 ) 10.9, H4), 6.25
(m, 1H, H3). (Z) 1H δ 5.42 (m, 1H, J H2-H3 ) 10.3, H2), 6.05 (bd,
1
1H, J H3-H4 ) 10.9, H4) 6.22 (m, 1H, H3). (E, Z) H δ 1.05 (m,
6H, H7, H7′), 1.77 (d, 3H, J H1-H2 ) 6.4, H1), 2-2.3 (m, 4H, H6,
H6′). (E) 13C δ 122.7 (CH), 126.7 (CH), 127.7 (CH), 143.9 (C-5).
(Z) 13C δ 117.7 (CH), 123.7 (CH), 125.3 (CH), 146.2 (C-5).
5-Meth yl-4-n on en e (21): two isomers in 1:1 ratio, 1H δ
0.88 (m, 6H, H1, H9), 1.27 (m, 4H, H3, H6), 1.33 (m, 6H, H2,
H7, H8), 1.58 (s, 3H, CH3-5, first isomer), 1.67 s, (3H CH3-5,
second isomer), 5.11 (bt, 1H, J H3-H4 ) 7.3, H4); first isomer,
13C δ 124.3 (CH), 135.5 (C-5); second isomer, 13C δ 125.0 (CH),
135.3 (C-5); both isomers, 13C δ 13.7, 13.8, 14.0, 15.8, 22.3,
22.6, 23.0, 23.2, 23.4, 29.9, 30.0, 30.2, 30.3, 31.5, 39.4.
5-Meth yl-2,4-n on a d ien e (22): pair of isomers 1, 1H δ 5.57
1-[(E,Z)-2′-Bu ten ylid en e]-4-eth ylcycloh exa n e (12): cis/
trans ) 33:66. H δ 0.88 (t, 3H, H8, J H8-H7 ) 7.1 Hz), 1.28 (m,
1
2H, H7), 1.74 (d, 3H, H4′, J H4′-H3′ ) 6.7 Hz), 1.70-1.95 (m, 4H,
H3, H5), 1.97-2.35 (m, 3H, H2, H4, H6), 2.74 (m, 2H, H2, H6),
5.31-5.47 (m, 1H, H3′ cis), 5.47-5.69 (m, 1H, H3′ trans), 5.73
(bd, 1H, H1′ trans, J H1′-H2′ ) 10.8 Hz), 6.05 (bd, 1H, H1′ cis,
J H1′-H2′ ) 11.5 Hz), 6.15-6.37 (m, 1H, H2′). 13C δ 11.5 (C-8),
13.01 (C-4′ cis), 18.2 (C-4′ trans), 27.9 (CH2), 28.2 (CH2), 28.3
(CH2), 29.3 (CH2), 33.5(CH2), 34.3 (CH2), 36.4 (CH2), 36.9 (CH2),
39.5 (C-4), 116.8 (CH cis), 121.8 (CH trans), 123.7 (CH cis),
124.9 (CH cis), 126.5 (CH trans), 127.4 (CH trans), 140.6 (C-1
trans), 142.8 (C-1 cis).
(m, 1H, H2), 5.78 (bd, 1H, J H3-H4 ) 10.8, H4), 6.2 (m, 1H, H3);
1
1-Bu tylid en e-4-ter t-bu tylcycloh exa n e (13): 1H δ 0.86 (s,
9H, 3 × CH3), 0.89 (t, 3H, H4′, J H4′-H3′ ) 7.3 Hz), 1.35 (m, 2H,
H3′), 1.65 (m, 1H, H4), 1.80-2.10 (m, 6H, H3, H5, H2′), 2.23 (m,
pair of isomers 2, H δ 5.42 (m, 1H, H2), 6.1 (bd, 1H, J H3-H4
)
10.8, H4), 6.2 (m, 1H, H3); both pairs, 1H δ 0.9 (m, 3H, H9),
1.05-1.55 (m, 4H, H7, H8), 1.75 (m, 6H, H1, CH3-5), 1.95-2.2
(m, 2H, H6).
2H, H2, H6), 2.65 (m, 2H, H2, H6), 5.07 (bt, 1H, H1′, J H1′-H2′
)
2-Bu tyl-1,3-d im eth yl-1-cycloh exen e (23): 1H δ 0.90 (t,
7.2 Hz). 13C δ 13.8 (C-4′), 23.4 (CH2), 27.7 (3 × CH3), 28.6 (2 ×
CH2), 29.3 (CH2), 29.4 (CH2), 32.5 (C-7), 37.1 (CH2), 48.7 (C-
4), 121.0 (C-1′), 139.5 (C-1).
3H, J H4′-H3′ ) 7.7, H4′), 0.98 (d, 3H, J CH
) 7.2, CH3-3), 1.3
H
3-
3
(m, 2H, H3′), 1.07-1.45 (m, 2H, H5), 1.58 (s, 3H, CH3-1), 1.8-
2.0 (m, 2H, H1′), 1.9 (m, 2H, H6), 2.1 (m, 1H, H3). 13C δ 14.2
(CH3), 19.2 (CH3), 19.5 (CH3), 19.9 (CH3), 22.6 (CH), 22.8 (CH2),
23.0 (CH2), 23.2 (CH2), 23.4, 24.5, 26.5 (CH2), 27.2 (CH2), 28.9
(CH2), 30.0 (CH), 30.8 (CH2), 31.2 (CH2), 31.3 (CH2), 31.5 (CH2),
32.1 (CH), 32.3 (CH2), 45.9 (CH), 121.6 (CH), 125.9, 134.9,
135.9.
Od or Eva lu a tion . Odor quality of undiluted samples was
judged by a panel of six expert perfumers. Subjective intensity
was evaluated on a five point scale and indicated with the
terms very weak, weak, medium, strong, and very strong.
1-[(E,Z)-2′-Bu ten ylid en e]-4-ter t-bu tylcycloh exa n e (14):
1H δ 0.93 (s, 9H, 3 × CH3), 1.84 (d, 3H, H4′, J H4′-H3′ ) 6.6 Hz),
1.85-2.05 (m, 5H, H3, H4, H5), 2.10-2.45 (m, 2H, H2, H6), 2.90
(m, 2H, H2, H6), 5.40-5.54 (m, 1H, H3′ cis), 5.54-5.78 (m, 1H,
H3′ trans), 5.80 (bd, 1H trans, J H1′-H2′ ) 10.6 Hz), 6.11 (bd,
1H, H1′ cis, J H1′-H2′ ) 11.6 Hz), 6.23-6.48 (m, 1H, H2′). 13C δ
13.0 (C-4′ cis), 18.2 (C-4′ trans), 27.6 (3 × CH3), 28.4 (CH2),
28.8 (CH2), 28.9 (CH2), 29.2 (CH2), 29.3 (CH2), 32.4 (C-7), 37.0
(CH2), 48.4 (C-4), 116.5 (CH cis), 121.4 (CH trans), 123.7 (CH
cis), 124.9 (CH cis), 126.6 (CH trans), 127.4 (CH trans), 140.6
(C-1 trans), 142.9 (C-1 cis). Cis/trans ) 29:71.
1-Bu tylid en ecycloh ep ta n e (15): 1H δ 0.89 (t, 3H, J H3′-H4′
) 7.3, H4′), 1.33 (m, 2H, H3′), 1.51 (bs, 8H, H3, H4, H5, H6),
1.94 (q, 2H, J H2′-H1′ ) 7.2, H2′), 2.2 (m, 4H, H2, H7), 5.13 (m,
1H, H1′). 13C δ 13.9 (CH3), 23.0 (CH2), 27.2 (CH2), 29.1 (CH2),
29.5 (CH2), 29.7 (CH2), 29.9 (CH2), 30.0 (CH2), 37.9 (CH2), 125.1
(C-1′), 141.0 (C-1).
1-[(E,Z)-2′-Bu ten ylid en e]cycloh ep ta n e (16): (E) 1H δ
1.55 (bs, 8H, H3, H4, H5, H6), 1.76 (d, 3H, J H4′-H3′ ) 6.5, H4′),
2.3 (m, 4H, H2, H7), 5.56 (m, 1H, J H2′-H3′ ) 15.1, J H3′-H4′ ) 6.5,
RESULTS AND DISCUSSION
Syn th esis of th e Od or a n ts. All of the compounds
reported in this work, except 23, were synthesized by
Wittig reaction from the corresponding ketones and the
appropriate bromide, using the general method reported
under Materials and Methods. In the cases where the
reaction gave a mixture of stereoisomers, these were not
separated, but the composition was evaluated by GLC.
Compounds 1 (Schlosser et al., 1986), 2 (Dehmlow et
al., 1981), 3 (Negishi and Miller, 1989), 5 (Crabbe et
al., 1978), 6 (Suzuka et al., 1991), 8 (Hanessian et al.,
1983), 13 (J ung et al., 1973), 14 (Hanessian et al., 1983),
15 (Schomburg, 1966), 18 (Gassman and Valcho, 1975),
and 21 (Kawai et al., 1990) have been already reported
in the literature, whereas the others, to the best of our
knowledge, have not been previously described.
The NMR spectra of the new compounds and of those
for which spectroscopic data are not available are
reported under Materials and Methods.
H3′), 5.77 (d, 1H, J H2′-H1′ ) 10.9, H1′), 6.3 (m, 1H, J H2′-H3′
)
1
14.9, H2′). (Z) H δ 1.55 (bs, 8H, H3, H4, H5, H6), 1.75 (d, 3H,
J H4′-H3′ ) 6.5, H4′), 2.3 (m, 4H, H2, H7), 5.47 (m, 1H, J H3′-H4′
)
6.6, H3′), 6.08 (d, 1H, J H1′-H2′ ) 11.8, H1′), 6.2 (m, 1H, J H2′-H3′
) 9.8, H2′). (E) 13C δ 18.3 (CH3), 29.0 (CH2), 30.2 (CH2), 37.9
(CH2), 124.9 (CH), 126.5 (CH), 127.8 (CH), 142.1(C-1). (Z) 13
C
δ 13.1 (CH3), 27.3 (CH2), 30.2 (CH2), 38.4 (CH2), 119.9 (CH),
123.5 (CH), 125.4 (CH), 144.4 (C-1).
1-[(E,Z)-2′-Bu ten ylid en e]cyclop en ta n e (17): (E and Z)
1H δ 1.6 (m, 4H, Hb, H4), 1.74 (d, 3H, J H4′-H3′ ) 7.3, H4′), 2.4
(m, 4H, H2-H5), 5.50 (m, 1H, J H3′-H2′ ) 13.9, J H3′-H4′ ) 7.3,
H3′), 5.85 (bd, 1H, J H1′-H2′ ) 8.7, H1′), 6.15 (m, 1H, J H2′-H1′
)
8.7, J H2′-H3′ ) 13.9, H2′). (E) 13C δ 18.2 (CH3), 26.2 (CH2), 29.2
(CH2), 33.8 (CH2), 120.2 (CH), 125.5 (CH), 129.4 (CH), 144.7
(C-1). (Z) 13C δ 13.1 (CH3), 26.3 (CH2), 34.2 (CH2), 115.6 (CH),
122.6 (CH), 127.1 (CH), 147.1 (C-1).
Olfa ctor y P r op er ties. Figure 1 reports the struc-
tures of all compounds synthesized, together with their
olfactory properties.
2-[(E,Z)-Bu tylid en e]bicyclo[2.2.1]h ep ta n e (18): 1H δ
0.84 (t, 3H, H4′), 0.87 (t, 3H, H4′), 1.15-1.45 (m, 6H, H5, H6,
H3′), 1.45-1.70 (m, 2H, H7), 1.7-2.4 (m, 5H, H3, H4, H2′), 2.6
The relationships between all of these odorants can
be analyzed with reference to a basic skeleton of
n-butylidenecyclohexane. Modifications on this basic
structure include the following: a second conjugated
double bond on the butylidene chain; a methyl group in
position 2, 3, or 4 or a larger group (ethyl or tert-butyl)
in position 4; a bridging carbon atom, modifying the
cyclohexane ring into a norbornane skeleton; a cyclo-
pentane or a cycloheptane ring in place of the cyclohex-
ane; and open-chain analogues, ideally derived from the
cyclohexane derivatives by cleaving one or two bonds.
1-Butyl-2,6-dimethylcyclohexene (23) is the only de-
rivative bearing a double bond in the ring, rather than
in the side chain.
(bs, 1H, H1 (E)), 2.90 (bs, 1H, H1 (Z)), 4.98 (bt, 1H, J H1′-H2′
)
7.3, H1′ (Z), 5.17 (bt, 1H, J H1′-H2′ ) 7.1, H1′ (E)). 13C δ 13.7 (CH3),
13.8 (CH3), 22.9 (CH2), 23.4 (CH2), 28.5 (CH2), 28.7 (CH2), 29.5
(CH2), 30.1 (CH2), 30.7 (CH2), 31.4 (CH2), 35.8 (CH2), 36.3 (CH),
36.6 (CH), 38.8 (CH2), 39.1 (CH2), 39.2 (CH2), 40.1 (CH), 43.0
(CH), 116.9 (C1′), 117.8 (C1′), 145.1 (C-2), 146.0 (C-2).
3-Eth yl-3-h ep ten e (19): 1H δ 0.98 (t, 3H, H7, J H6-H7 ) 7.4
Hz), 1.08 (t, 6H, H1, H1′, J H2-H1′,H2′-H1′ ) 7.3 Hz), 1.54 (m, 2H,
H6), 1.85 (m, 2H, H5), 2.05 (bq, 4H, H2, H2′, J H1-H2,H1′-H2′ ) 7.4
Hz), 5.10 (bt, 1H, H4, J H4-H5 ) 7.3 Hz). 13C δ 10.6 (C-1, C-1′),
14.7 (C-7), 23.1 (CH2), 27.1 (CH2), 30.4 (CH2), 31.0 (CH2), 124.6
(C-4), 143.6 (C-3).

1288 J. Agric. Food Chem., Vol. 48, No. 4, 2000
Anselmi et al.
reported can be prepared in good yields from simple
starting compounds and therefore are more easily
accessible than the megastigmatrienes.
The fruity odor is usually associated with the presence
of an ester group and represents one of the few examples
of odors depending more on the type of functional group
than on stereochemical parameters of the molecule. It
is therefore rather unexpected to find such olfactory
notes in molecules as different from esters as the
hydrocarbons here described. Moreover, the fruity odor
of these compounds depends, to a large extent, on the
shape of the molecule, unlike the case of esters.
The derivatives with two conjugated double bonds
possess in some cases more characteristic notes and in
general have stronger odors than their monoene ana-
logues. Their main fruity character prompts a compari-
son with esters of similar structure. In cyclohexyl
propionate, butyrate, and isobutyrate, the predominant
fruity character is associated with secondary floral
notes, having an overall sensation reminiscent of pine-
apple or banana. These observations indicate that the
alkene molecules endowed with fruity odor interact with
their receptor protein in a specific fashion and with a
definite orientation. A comparison between the struc-
tures of these hydrocarbons and esters of related
structure further suggests that the π-electron-rich area,
corresponding to the conjugated double bonds in the first
class of molecules and to the ester group in the other,
may play similar roles in their interactions with specific
groups in the receptor proteins. If this hypothesis is
correct, then the presence and the position of the double
bond should be essential for the fruity odor of the
molecule. Saturated hydrocarbons, in fact, do not exhibit
characteristic odors but notes generally described as
“gassy” or “petrol”.
F igu r e 1. Structures and odor properties of the unsaturated
hydrocarbons prepared. VS, very strong; S, strong; M, medium;
W, weak; VW, very weak. Compound 23 contained ∼20% of
its isomer 2,5-dimethyl-1-butylidenecyclohexane.
The mixed fruity/floral character of these unsaturated
hydrocarbons also suggests that other alkenes may
present a stronger floral character and could be the
basis for a search of floral-smelling hydrocarbons. In
fact, a comparison between the structures of the odor-
ants presented in this work and those of floral-smelling
derivatives previously reported (Anselmi et al., 1992,
1993, 1994) reveals common elements, such as the
4-substituted cyclohexane ring, that may be more
directly related to the floral character in both classes
of odorants.
We can observe that most of the variations generally
do not appreciably modify the olfactory character com-
mon to these alkenes, a fruity/green note, with a floral
character. A slightly smaller or larger ring, as well as
the presence of a fused ring system, such as the
norbornane of derivative 18, does not introduce major
changes in their odor. A bulkier alkyl group in position
4 of the ring, instead, has a marked effect. Although
the ethyl derivatives 11 and 12 retain the fruity and
green characters, these notes are completely lost in the
tert-butyl derivatives 13 and 14, the odors of which are
described as fatty and rubbery. The presence of a ring
also seems to be essential for the fruity odor; this
disappears or is present only as a secondary note in the
four open-chain analogues 19-22.
ACKNOWLEDGMENT
We thank Dr. Marco Mariani of Curti-Georgi Imes
International Flavor and Dr. Karen Rossiter of Quest
International for the olfactory evaluations.
LITERATURE CITED
A more detailed analysis of the olfactory properties
indicates that the pleasant fruity/floral note, charac-
teristic of the megastigmatrienes, is reproduced, to some
extent, in several derivatives synthesized in this work.
Although for an experienced perfumer the odors of the
megastigmatrienes are easily distinguishable from those
of their simpler analogues, here reported, it is neverthe-
less interesting to observe that the basic pleasant
character of “tropical fruit” is present in several other
hydrocarbons. A ring structure of about six carbon
atoms seems to be essential, as is a chain of at least
four carbon atoms. The fruity note is present in both
monoene and diene derivatives, whereas methyl groups
present in different positions of the ring seem not to be
of major consequence to the odor. The odorants here
Amoore, J . E. Specific anosmia: a clue to the olfactory code.
Nature 1967, 214, 1095-1098.
Anselmi, C.; Centini, M.; Mariani, M.; Sega, A.; Pelosi, P. Odor
properties of some tetrahydropyranyl ethers. J . Agric. Food
Chem. 1992, 40, 853-856.
Anselmi, C.; Centini, M.; Mariani, M.; Sega, A.; Pelosi, P.
Influence of regio- and stereochemistry on the floral odor of
THP and THF ethers. J . Agric. Food Chem. 1993, 41, 781-
784.
Anselmi, C.; Centini, M.; Mariani, M.; Napolitano, E.; Sega,
A.; Pelosi, P. Synthesis of ethers related to some floral
odorants: effect of oxygen/carbon replacement. J . Agric.
Food Chem. 1994, 42, 2876-2879.
Arctander, S. Perfume and Flavour Chemicals; Arctander:
Elizabeth, NJ , 1969.

Hydrocarbon Odorants
J. Agric. Food Chem., Vol. 48, No. 4, 2000 1289
Beets, M. G. J . Structure-Activity Relationships in Human
Chemoreception; Applied Sciences Publishers: London, U.K.,
1978.
Blank, I.; Grosch, W. Evaluation of potent odorants in dill seed
and dill herb (Anethum graveolens L.) by aroma extract
dilution analysis. J . Food Sci. 1991, 56, 63-67.
Buck, L.; Axel, R. A novel multigene family may encode
odorant receptors: a molecular basis for odor recognition.
Cell 1991, 65, 175-187.
Carlson, D. A.; Offor, I. I.; ElMessoussi, S.; Matsuyama, K.;
Mori, K.; J allon, J . M. Sex pheromone of Glossina tachi-
noide: Isolation, identification and synthesis. J . Chem. Ecol.
1998, 24, 1563-1575.
Crabbe, P.; Dollat, J . M.; Gallina, J .; Luche, J . L.; Velarde, E.;
Maddox, M. L.; Tokes, L. Steric course of cross coupling of
organocopper reagents with allylic acetates. J . Chem. Soc.,
Perkin Trans. 1978, 730-734.
Dehmlow, Eckehard, V.; Barahona-Naranjo, S. Applications
of phase transfer catalysis. Part 17. Wittig reactions in
various two-phase systems. J . Chem. Res. Synop. 1981, 142.
Gassman, P. G.; Valcho, J . J . Chemistry of bent bonds. XLV.
Norbornyne. J . Am. Chem. Soc. 1975, 97, 4768-4770.
Hanessian, S.; Bennant, Y. L.; Leblanc, Y. Efficient olefination
with R-alkylcyclic phosphonamides. Heterocycles 1983, 35,
1411-1424.
J ung, F.; Sharma, N. K.; Durst, T. b-Sultines. Intermediates
in a sulfur analog of the Wittig olefin synthesis. J . Am.
Chem. Soc. 1973, 95, 3420-3422.
Kawai, T.; Maruoka, N.; Ishikawa, T. Reaction behaviour in
metathesis of alkenes with alkyl-substituted vinylene struc-
ture over CsNO3-Re2O7-Al2O3 catalyst. J . Mol. Catal. 1990,
60, 209-219.
Negishi, E.; Miller, S. R. Stereoselective synthesis of exocyclic
alkenes via ammonium promoted alkyl-diene coupling. J .
Org. Chem. 1989, 54, 6014-6016.
Ohloff, G. Riechstoffe und Geruchssinn; Springer-Verlag: Ber-
lin, Germany, 1990.
Pelosi, P.; Pisanelli, A. M. Specific anosmia to 1,8-cineole: the
camphor primary odor. Chem. Sens. 1981, 6, 87-93.
Rossiter, K. J . Structure-odor relationships. Chem. Rev. 1996,
96, 3201-3240.
Schlosser, M.; Schaub, B.; De Oliveira-Neto, J .; J eganathan,
S. Practical guidance for obtaining optimum cis-selectivities
in Wittig reactions with triphenylphosphonio-alkanides.
Chimia 1986, 40, 244-245.
Schomburg, G. Gas-chromatographic retention data and struc-
ture of chemical compounds. II. Methyl branching and
double bonds in open chain hydrocarbons. J . Chromatogr.
1966, 23, 1-17.
Suzuka, Hiroyasu; Hattori, H. Cross-dehydrocycloaddition of
1,3-butadiene with isoprene over magnesium oxide and
zirconium oxide. Bull. Chem. Soc. J pn. 1991, 64, 1332-
1335.
Theimer, E. T. Fragrance Chemistry. The Science of the Sense
of Smell; Academic Press: New York, 1982.
Whitfield, F. B.; Sugowdz, G. The 6-(but-2′-enylidene)-1,5,5-
trimethylcyclohex-1-enes: important volatile constituents
of the juice of the purple passionfruit. Aust. J . Chem. 1979,
32, 891-903.
Zhao, H.; Ivic, L.; Otaki, J . M.; Hashimoto, M.; Mikoshiba, K.;
Firestein, S. Functional expression of a mammalian odorant
receptor. Science 1998, 279, 237-242.
Received for review October 25, 1999. Revised manuscript
received J anuary 12, 2000. Accepted J anuary 13, 2000. This
research was supported by a grant (Ricerca Scientifica 60%)
of the University of Siena.
Malnic, B.; Hirono, J .; Sato, T.; Buck, L. B. Combinatorial
receptor codes for odors. Cell 1999, 96, 713-723.
Mu¨ller, P. M.; Lamparski, D. Perfumes: Art, Science, Technol-
ogy; Blackie Academic & Professional: London, U.K., 1994.
J F991156P