Novel convenient synthesis of (Z/E)-8-dodecenyl acetates, components of the Grapholitha molesta sex pheromone

Article abstract of DOI:10.1007/s10600-006-0263-7

Components of the Grapholitha molesta sex pheromone, (Z/E)-8-dodecenyl acetates (1, 2), were synthesized in five steps in 20% overall yield using 10-hydroxydecanoic acid (3) as starting material.

Full text of DOI:10.1007/s10600-006-0263-7

Chemistry of Natural Compounds, Vol. 42, No. 6, 2006
NOVEL CONVENIENT SYNTHESIS OF ( / )-8-DODECENYL
Z E
ACETATES, COMPONENTS OF THE
SEX PHEROMONE
Grapholitha molesta
G. Z. Huang,1,2 J. M. Li,1,2 J. L. Lu,1,2 and H. A. Aisa1
UDC 542.943+547.31
Grapholitha molesta
Z/E
1 2
Components of the
sex pheromone, ( )-8-dodecenyl acetates ( , ), were synthesized
3
in five steps in 20% overall yield using 10-hydroxydecanoic acid ( ) as starting material.
Key words: sex pheromone,
, 8-dodecenyl acetate, ozonolysis.
Grapholitha molesta
, or Oriental fruit moth, is a pest of peaches, apples, pears, apricots, etc. About 40 years ago its
Grapholitha molesta
pheromone component was isolated [1] and identified [2] as ( )-8-dodecenyl acetate (1, Scheme 1). Many researchers found
Z
that sex pheromone 1 that contains from 5 to 10% of the ( )-isomer (2) is still biologically active [3, 4].
E
a
b
c
OH
OH
AcO
O
Br
HO
AcO
4
O
O
5
3
d
e
AcO
AcO
6
7
O
O
+
O
O
1 (Z)
2 (E)
a) pyridine, Ac2O, room temperature, 24 h; b) HgO, Br2, CCl4, irradiation by tungsten lamps, 200 W, 4 h; c) LiBr, Li2CO3, DMF, 130°C,
6 h; d) O3, CH2Cl2, then Zn/H2O/CH3COOH; e) BuLi, n-butyltriphenylphosphonium bromide, dry THF, 18-25°C.
Compounds 1 and 2 can be used as attractants of other insects such as
,
,
Cryptophlebia batrachopa G. leucotreta
,
,
, etc. [5-8]. Leal et al. discovered in 2001 that the ( )-isomer is the main
G. funebrana G. lobarzewskii Eucosma notanthes
E
component of the sex pheromone of
[9].
Ecdytolopha aurantiana
The synthesis of components of
sex pheromone has been reported [3, 4, 10-15]. The shortest pathway to
G. molesta
the acetylene compounds consists of Wittig olefination of 8-acetoxyoctanal by -butyltriphenylphosphonium bromide. The
n
difficulty in this instance is the preparation of 8-acetoxyoctanal. The synthesis of the pheromones used 1,8-octanediol, which
is monoacetylated for use as a precursor in the synthesis of the target molecule. Then this compound is oxidized by pyridinium
chlorochromate. However, the monoacetylation of 1,8-octanediol is difficult to carry out successfully because the diacetyl
derivative can be produced simultaneously with the monoacetyl derivative. Another drawback is the contamination of the
reaction mixture with pyridinium chlorochromate.
Herein we report a more efficient method for synthesizing components of
sex pheromone. Scheme 1 shows
G. molesta
the total synthesis of 1 and 2, which includes five steps. The ( )- and ( )-components were synthesized starting from
Z
E
10-decanoic acid (3), which was prepared bythe literature method [16]. After protection of the hydroxyl in 3, esterification with
acetic anhydride in pyridine produced 10-acetoxydecanoic acid (4). Then a classical Hunsdiecker reaction of 4 gave
1) Xinjiang Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Urumqi 830011, China, fax
+86 991 3835679, e-mail: haji@ms.xjb.ac.cn; 2) Graduate School ofthe Chinese Academyof Sciences, Beijing 100041, China.
Translated from Khimiya Prirodnykh Soedinenii, No. 6, pp. 592-594, November-December, 2006. Original article submitted
July 21, 2006.
0009-3130/06/4206-0727 ©2006 Springer Science+Business Media, Inc.
727

alkylbromide 5. Elimination of HBr upon reaction of5 with LiBr and Li CO produced 6 with a terminal methylene, ozonolysis
2
3
of which gave key intermediate 7 (8-acetoxyoctanal), from which reaction with n-butyltriphenylphosphonium bromide under
conditions for n-butyllithium produced 1 and 2.
Thus, we demonstrated a novel and convenient pathway to the target compounds. Furthermore, 7 can be used to
prepare a series of 8-alkenylacetates.
EXPERIMENTAL
IR spectra were recorded in KBr disks on an Bruker Equinox 55 spectrophotometer. PMR spectra in CDCl were
3
obtained on a Varian 400 spectrophotometer with TMS internal standard. Column chromatography used silica gel (200-
300 mesh) from Yantai Jiangyou Silica Development Co. Ltd. All solvents were analytically pure.
10-Acetoxydecanoic Acid. 10-Hydroxydecanoic acid (9.4 g, 0.05 mol) was acetylated by acetic anhydride (10 mL)
in pyridine (10 mL) with stirring at room temperature for 24 h. The reaction mixture was poured into icewater (50 mL) and
extracted with ether. The organic layer was washed with water (20 mL) and saturated brine (20 mL), dried over anhydrous
Na SO , and evaporated in vacuo. The reaction products were purified by flash chromatography with elution by petroleum
2
4
ether:ethylacetate (30:1) to afford 4 (10.69 g, 93%), colorless oil. PMR spectrum (CDCl , δ, ppm, J/Hz): 1.31 [10H, m,
3
–(CH ) -], 1.62 (4H, m, 3-CH , 9-CH ), 2.05 (3H, s, COCH ), 2.35 (2H, t, J = 7.6, CH COO), 4.05 (2H, t, J = 6.8, CH OAc).
2 5
2
2
3
2
2
The COOH proton was not observed because of rapid exchange with water of the solvent.
9-Bromononyl Acetate (5). A mixture of 10-acetoxydecanoic acid (4, 4.6 g, 0.02 mol), HgO (6.5 g, 0.035 mol), and
Br (1.5 mL) in CCl (120 mL) was irradiated bytwo tungsten lamps (100 W) with stirring on a magnetic stirrer. The reaction
2
4
was carried out under N for 4 h in a flask equipped with a reflux condenser. The resulting solution was cooled to room
2
temperature; washed with aqueous NaHSO (10%, 3 × 10 mL), saturated aqueous NaHCO (3 × 10 mL), and brine (2 × 20 mL);
3
3
dried over anhydrous Na SO ; and evaporated in vacuo. The product was purified by flash chromatography with elution by
2
4
petroleum ether:ethylacetate (30:1) to afford 5 (4.13 g, 78%), yellow oil. PMR spectrum (CDCl , δ, ppm, J/Hz): 1.31 [10H, m,
3
–(CH ) –], 1.62 (2H, m, 8-CH ), 1.85 (2H, m, 2-CH ), 2.05 (3H, s, COCH ), 3.41 (2H, t, J = 6.4, CH Br), 4.05 (2H, t, J = 6.4,
2 5
2
2
3
2
CH OAc).
2
8-Nonenyl Acetate (6). A stirred suspension of dry LiBr (0.4 g) and Li CO (0.26 g) in dry DMF (15 mL) at 120°C
2
3
was treated with 5 (1.92 g, 0.007 mol). The reaction was carried out under N for 6 h. The resulting mixture was
2
cooled, poured into dilute acetic acid, and extracted with CH Cl . The extract was washed with water (2 × 10 mL) and brine
2
2
(2 × 10 mL), dried over anhydrous Na SO , and evaporated in vacuo. The product was purified by flash chromatography with
2
4
elution by petroleum ether:ethylacetate (100:1) to afford 6 (1.04 g, 81%), colorless oil. PMR spectrum (CDCl , δ, ppm, J/Hz):
3
1.36 [8H, m, –(CH ) –], 1.62 (2H, m, 8-CH ), 2.03 (5H, m, 7-CH , COCH ), 4.05 (2H, t, J = 6.4, CH OAc), 4.95 (2H, m,
2 4
2
2
3
2
CH CH), 5.80 (1H, m, CH CH).
2
2
8-Acetoxyoctan-1-al (7). A solution of 6 (1.82 g, 0.01 mol) in CH Cl (25 mL) was placed in a three-necked round-
2
2
bottomed flask, cooled to -40°C in liquid N , and ozonized with a stream of O (50 mL/min, 5 g/h). The completion of the
2
3
reaction was determined by testing with KI starch paper. Then the flask with the reaction mixture was purged with N for
2
10 min to remove the excess of O . The cooling bath was removed. The reaction mixture was stirred; purged with N ; treated
3
2
with Zn dust (2.7 g, 0.042 mol), acetic acid (2mL), and water (6 mL); and slowly brought to room temperature. The solution
was filtered. The aqueous layer was extracted with ethylacetate (3 × 10 mL). The organic layer was washed with saturated
aqueous NaHCO , water, and brine; dried over anhydrous Na SO , and evaporated in vacuo. The product was purified byflash
3
2
4
chromatography with elution by petroleum ether:ethylacetate (30:1) to afford 7 (1.32 g, 71%), colorless oil. PMR spectrum
(CDCl , δ, ppm, J/Hz): 1.32 [6H, m, –(CH ) –], 1.59 (4H, m, 3-CH , 7-CH ), 2.02 (3H, s, COCH ), 2.40 (2H, tt, CH CHO),
3
2 3
2
2
3
2
4.02 (2H, t, J = 6.8, CH OAc), 9.74 (1H, t, J = 1.6, CHO).
2
(Z/E)-8-Dodecenyl Acetates (1 and 2). A suspension of n-butyltriphenylphosphonium bromide (10.6 g, 0.027 mol)
in dry THF (40 mL) at 18°C under N was treated with n-butyllithium in hexane (2.5 M, 11 mL, 0.027 mol). The mixture was
2
stirred at 18°C for 2 h, treated with 7 (3.16 g, 0.017 mol), stirred at 18°C for 2 h and overnight at room temperature. The
reaction mixture was saturated with saturated NH Cl solution and filtered. The organic layer was washed with water and brine,
4
dried over anhydrous Na SO , and evaporated in vacuo. The product was purified bychromatographywith elution bypetroleum
2
4
ether:ethylacetate (100:1) to afford 1 and 2 (1.85 g), yellowish oil. GC of the components determined that the ratio of Z- and
728

-1
E-isomers was 72.5:27.5. Overall yield 48.2%. IR spectrum (ν , cm ): 3005, 2929, 2856, 1743, 1462, 1366, 1239, 1041,
max
970, 723. PMR spectrum (CDCl , δ, ppm, J/Hz): 0.905 (3H, t, J = 7.6, 12-CH ), 1.36 [10H, m, 11-CH , –(CH ) –], 1.60 (2H,
3
3
2
2 4
m, 2-CH ), 2.00 (7H, m, COCH , 7-CH , 10-CH ), 4.05 (2H, t, J = 6.8, CH OAc), 5.36 (2H, m, CH=CH).
2
3
2
2
2
ACKNOWLEDGMENT
The synthesis of sex pheromones was carried out in the Xinjiang Technical Institute of Physics and Chemistry of the
Chinese Academy of Sciences. The work was supported by the program for development and research of high technologies in
Xinjiang, Project (O539161401).
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