628 油 化 学

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A Convenient Synthesis of Methyl Jasmonate

and γ-Jasmolactone

Use of 3-Cyanopropionaldehyde Dimethyl Acetal

(3-Cyano-1, 1-dimethoxypropane) Derivatives
as Precursors of
1, 4-Dicarbonyl Compounds

Takashi YOSHIDA*, Tetsuo MIYAKOSHI, and Shojiro SAITO

* NipponDentalUniversity at Niigata(1-8, Hamaura-cho,
Niigata-shi)
Departmentof IndustrialChemistry,
Facultyof Engineering,
Meiji
University
(1-1-1,Higashimita,Tama-ku,Kawasaki-shi)

Methyl jasmonate and γ-jasmolactone, as important perfumery constituents, were synthesized

from a readily available starting material, 3-cyano-1, 1-dimethoxypropane (1). The synthetic route
is shown in Scheme-1.
The reaction of (1) with cis-3-hexenylmagnesium bromide gave 1, 1-dimethoxy-cis-7-decen-4-one
(4) in 54% yield. Deacetalization of (4) followed by cyclization afforded 2-(cis-2-pentenyl)-2-
cyclopenten-1-one (6) in 48.6% yield. Methyl jasmonate (7) was obtained from (6) in 65% yield.
γ-Jasmolactone (8) was synthesized by an one-pot reaction of methyl 4-oxobutyrate (3) with cis-

3-hexenylmagnesium bromide in 69% yield.

of jasmonoids and insect pheromone utilizing

1 Introduction readily available sulfones.2)∼5) We found that

Jasmonoids such as cis-jasmone, methyl jas- 3-cyano-1, 1-dimethoxypropane (1), methyl 4, 4

monate, and γ-jasmolactone, etc., are valuable -dimethoxybutyrate (2) , and methyl 4-oxobu-
compounds as jasmine perfumes. Many reports tyrate (3) were good and readily available
were published on the synthesis of jasmonoids.1) starting materials for the synthesis of jasmo-
In our previous papers, we reported the synthesis noids. In connection with our studies on the
preparation of terpenes, perfumery, and
flavor substances, we reported in this paper
the synthesis of methyl jasmonate and γ-

jasmolactone by reactions of (1) or (3)

with Grignard reagent.

2 Experimental
2・1 Analytical Apparatus
Boiling points are uncorrected. Infrared
spectra were recorded on a Hitachi 260-30
spectrophotometer. 1H-NMR spectra were
measured on a Varian EM-390 spectrometer
at 90MHz, using CCl4 as a solvent and
TMS as an internal standard.
Scheme-1 2・2 Methyl 4, 4-dimethoxybutyrate (2)

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 第33巻 第9号 (1984) 629

To a 500ml round-bottomed flask fitted with t ure and for 2h at room temperature, the
a magnetic stirrer and a reflux condenser was mixture was stirred for 2h under gentle reflux.
charged (1) (30g, 0.29mol) and 10% NaOH Then the reaction mixture was cooled, diluted
(200ml). The mixture was heated under reflux with 50ml of ether, and hydrolyzed by the
for 8h, acidified with conc. HCl, and extracted addition of excess saturated NH4Cl. The ether
with chloroform (100ml×4). The combined layer was separated, dried over anhydrous
chloroform solution was evaporated in vacuo to sodium sulfate, and concentrated to give crude
give a crude product, which was added to (4), which was distilled to give pure 1, 1-
methanol (100ml) containing conc. H2SO4 (0.5 dimethoxy-cis-7-decen-4-one (4) (2.4g, 54%
g) and the mixture was refluxed for 5h. After yield), bp 111∼112℃/3mmHg. The IR and
evaporation of methanol, the reaction mixture 1 H-NMR spectra of (4) were identical with
was diluted with water and extracted with ether. those of the authentic sample.
The extract was washed with 5% NaHCO3 and 2・5 4-Oxo-cis-7-decenal (5)

water, dried over anhydrous sodium sulfate, 4-Oxo-cis-7-decenal (5) was obtained in 90%
and concentrated. The residue was distilled yield from (4) in a simmilar manner as described
under reduced pressure to give methyl 4, 4- in our previous paper2), bp 103∼104℃/4mmHg.
dimethoxybutyrate (2) (30g) in 80% yield, bp The IR and 1H-NMR spectra of (5) were in
61∼62℃/5mmHg. IR (neat) 2930, 1745, 1435, agreement with those of the authentic sample.
1355, 1250, 1110, 1050cm-1. 1H-NMR (CCl4) 2・6 2-(cis-2-Pentenyl)-2-cyclopenten-1-

1.7∼2.0 (2H, CH2, m), 2.30 (2H, CH2CO, one (6)

t, J=6.9Hz), 3.28 (6H, CH3O×2, s), 3.65 2-(cis-2-Pentenyl)-2-cyclopenten-1-one (6)

(3H, CH3OOC, s), 4.34 (1H, CH, t, J=4.2 was obtained in 60% yield from (5) in a sim-
Hz). milar manner as described in our previous
Found: C, 51.50; H, 8.81%. Calcd for paper2), bp 125℃ (bath)/4mmHg (let6)., bp
C7H14O4: C, 51.84; H, 8.70%. 7 0℃/0.05mmHg).

2・3 Methyl 4-oxobutyrate (3) The IR and 1H-NMR spectra of (6) were in
To a 50ml round-bottomed flask equipped agreement with those of the authentic sample.
with a magnetic stirrer and a reflux condenser 2・7 Methyl jasmonate (7)
was charged (2) (4g, 0.025mol) and distilled The cyclopentenone (6) was converted into
water (16ml). The mixture was refluxed for methyl jasmonate (7) in 65% overall yield by
8h. After cooling, the reaction mixture was a known procedure, bp 111∼112℃/5mmHg
extracted with chloroform. The extract was (let6)., bp 88∼90℃/0.01mmHg).
distilled to give methyl 4-oxobutyrate (3) (2.6 The IR and 1H-NMR spectra of (7) were
g) in 90% yield, bp 81∼82℃/26mmHg. IR identical with those of the authentic sample.
(neat) 2950, 2850, 2740, 1720, 1440, 1370, 2・8 γ-Jasmolactone (8)
1180, 1040cm-1. 1H-NMR (CCl4) 2.5∼2.9 (4 A dry THF (15ml) solution of 1-bromo-cis-
H, CH2CH2, m), 3.67 (3H, CH3OOC, s), 9.80 3-hexene (1.6g, 9.8mmol) was added dropwise
(1H, CHO, s). to a stirred mixture of dry magnesium turnings
Found: C, 51.57; H, 6.85%. Calcd for (0.23g, 9.6mmol) and dry THF (3ml) under
C5H8O3: C, 51.72; H, 6.94%. nitrogen at 0℃. After the addition had been

2・4 1, 1-Dimethoxy-cis-7-decen-4-one (4) completed, a dry THF (10ml) solution of (3)

A dry THF (20ml) solution of 1-bromo-cis (1.0g, 8.6mmol) was slowly added. The mix-
-3-hexene (4 .2g, 0.026mol) was added drop- ture, after being stirred for 1h at ice-bath
wise to a stirred mixture of dry magnesium temperature and for 1h at room temperature,
turnings (0.3g, 0.025mol) and dry THE (3ml) was added to saturated NH4Cl (5ml) and
under nitrogen at 0℃. After the addition had stirred for 15h at room temperature. To the
been completed, a dry THF (15ml) solution of mixture was added ether (50ml), and the ether
(1) (3.0g, 0.023mol) was added dropwise to layer was separated, dried over anhydrous so-
the Crignard reagent cooled in an ice-bath. dium sulfate, and concentrated to give crude
After being stirred for 1h at ice-bath tempera- (8) [(8):(9)=9.7:0.3]. The crude (8) was

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 630 油 化 学

distilled to give pure (8) (1.0g, 69% Yield), Table-1 Effect of work-up condition on the reac-
bp 96∼97℃/3mmHg. tion of methyl 4-oxobutyrate (3) with
The IR and 1H-NMR spectra of (8) were in cis-3-hexenylmagnesium bromide.

agreement with those of the authentic sample.

3 Results and Discussion

It was found that the treatment of 3-cyano-
1, 1-dimethoxypropane (1) with dii. acid (1%
HCl) gave no 3-cyanopropanal, but (1) almost
polymerized. When (1) was refluxed in distilled
water for 5∼8h, 3-cyanopropanal was obtained
Reaction conditions:
Solvent: THF, (4): 8.6mmol, 1-Bromo-cis-3-
in only 10% yield. Thus, methyl 4, 4-dimeth-
hexene: 9.8mmol, Mg: 9.6mmol, Temp.:
oxybutyrate (2) was prepared in 80% yield
0℃ →r.t.
by an alkaline hydrolysis of the cyano group a) 5ml was used.
of (1) and following esterification in methanol b) Based on methyl 4-oxobutyrate (3).
(Scheme-1). The compound (2) was refluxed c) The ratio of products was determined from
in distilled water for 8h to afford methyl 4- gas chromatography.
oxobutyrate (3) in 90% yield. d) Yield as a mixture of (8) and 9).

The first step of synthetic process of methyl e) Yield of isolated product.

jasmonate (7) is a reaction of (1) with cis-3-

of methyl jasmonate and γ-jasmolactone de-
hexenylmagnesium bromide in dry THF to give
scribed above are convenient and easy procedures.
1, 1-dimethoxy-cis-7-decen-4-one (4) in 54%
Particulaly, γ-jasmolactone was obtained by an
yield. Deacetalization of (4) with 5% HCl
one-pot Grignard reaction. The utilization of
gave 4-oxo-cis-7-decenal (5) in 90% yield.
Cyclization of (5) with 1% NaOH afforded 2- (2) and (3) for the synthesis of perfumery and
insect pheromone is under further investigation.
(cis-2-pentenyl)-2-cyclopenten-1-one (6) in 60%
yield. Michael addition of dimethyl malonate Acknowledgment
to (6) by using sodium methoxide in methanol
We would like to thank Mr. Hiroaki Omichi of
and the successive decarboxylative hydrolysis of
Meiji University for his valuable discussion and useful
the ester group, and esterification with methanol,
suggestions during this work.
gave methyl jasmonate (7) in 65% yield. (Received May 28, 1984)
We found that γ-jasmolactone (8) was ob-

tained by an one-pot Grignard reaction of (3) References

with cis-3-hexenylmagnesiun bromide. The de- 1) R.A. Ellison, Synthesis, 1973, 397; T.-L. Ho,
tailed conditions for the hydrolysis were sum- Synth. Commun., 4, 265 (1974); S. Torii and
marized in Table-1. H. Tanaka, Koryo, 114, 41 (1976).
Immediately after the addition of saturated 2) T. Yoshida and S. Saito, Yukagaku, 32, 82

NH4Cl to a reaction mixture, the ratio of (8): (1983).

3) T. Yoshida and S. Saito, Bull. Chem. Soc.
(9) was 7:3. When saturated NH4Cl was added Jpn., 55, 3931 (1982).
to the reaction mixture and then stirred for a
4) T. Yoshida and S. Saito, Chem. Lett., 1982,
long time, the ratio of γ-jasmolactone (8)
165.
increased gradually. After 15h, the ratio of 5) T. Yoshida and S. Saito, Bull. Chem. Soc.
(8):(9) was 9.7:0.3, based on gas chroma- Jpn., 55, 3047 (1982).
tographic analysis. Compounds (8) and (9) 6) G. Buchi and B. Egger, J. Org. Chem., 36,
could be separated by distillation. It was ob- 2021 (1971).

served, further, that the treatment of a mixture

of (8) and (9) with dilute NaOH and successive
neutralization with dilute HCl resulted in that
all (9) converted into γ-Jasmolactone (8).

In conclusion, the methods for the synthesis

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