Improved synthesis of (Z,E)-9,11,13-tetradecatrienal, the sex pheromone of the Carob Moth Apomyelois (=Ectomyelois) ceratoniae (Lepidoptera: Pyralidae)

Article abstract of DOI:10.3184/174751917X14894997017450

(Z,E)-9,11,13-Tetradecatrienal is a sex pheromone component emitted by virgin females of the Carob Moth Apomyelois ceratoniae Zeller (Lepidoptera: Pyralidae) which is an important pest of Iranian pomegranate fruits. Chemical control of this pest is not possible and biological methods with pheromones are used. The synthesis of the major component of the sex pheromone was achieved in fewer steps and with lower cost than previously. (Z,E)-9,11,13-Tetradecatrienal was synthesised by four steps with 59% overall yield. The coupling of a conjugated dienynol intermediate from E-1,2-dichloroethylene with vinyl magnesium bromide was achieved in good yield and followed by reduction of dienynol with activated zinc in THF-H₂O and oxidation gave the aldehyde of the sex pheromone.

Full text of DOI:10.3184/174751917X14894997017450

JOURNAL OF CHEMICAL RESEARCH 2017
VOL. 41 APRIL, 199–201
RESEARCH PAPER 199
Improved synthesis of (Z,E)-9,11,13-tetradecatrienal, the sex pheromone
of the Carob Moth Apomyelois (=Ectomyelois) ceratoniae (Lepidoptera:
Pyralidae)
a
b
c
b
Saeede Noorbakhsh , Babak Heidary Alizadeh *, Moosa Saber andHossein Farazmand
a
Department of Plant Protection, Faculty of Agriculture, University of Maragheh, Maragheh, Iran
Iranian Research Institute of Plant Protection, Agricultural Research, Education and Extension Organization (AREEO), Tehran, Iran
Department of Plant Protection, Faculty of Agriculture, University of Tabriz, Tabriz, Iran
b
c
(
(
Z,E)-9,11,13-Tetradecatrienal is a sex pheromone component emitted by virgin females of the Carob Moth Apomyelois ceratoniae Zeller
Lepidoptera: Pyralidae) which is an important pest of Iranian pomegranate fruits. Chemical control of this pest is not possible and
biological methods with pheromones are used. The synthesis of the major component of the sex pheromone was achieved in fewer steps
and with lower cost than previously. (Z,E)-9,11,13-Tetradecatrienal was synthesised by four steps with 59% overall yield. The coupling of
a conjugated dienynol intermediate from E-1,2-dichloroethylene with vinyl magnesium bromide was achieved in good yield and followed
by reduction of dienynol with activated zinc in THF-H O and oxidation gave the aldehyde of the sex pheromone.
2
Keywords: synthesis, sex pheromone, stereoselective reduction
(
Z,E)-9,11,13-Tetradecatrienal was isolated and synthesised by
The former major component has been synthesised in several
10,11
Millar (1990) as a component of the sex pheromone of the female
Carob Moth, Apomyelois ceratoniae. This insect is a worldwide
pest of nuts and fruits including, in the United States, carobs,
almonds, and dates. Moreover, in other parts of the world, this
species is a primary pest of dates, almond and pistachio, and in
steps.
Our synthesis of (Z,E)-9,11,13-tetradecatrienal
1
1
improved the yield and removed two steps which had limited
its availability and were costly. We synthesised the major trienal
aldehyde in a shorter route in which the conjugated double bonds
(
C9) were introduced with a high degree of stereochemical
2
,3,4
Iran, an important pest of pomegranates.
Mining by larvae
control (Fig. 1).
can damage the fruit introducing fungal saprophytes, rendering
the fruit unacceptable for the fresh fruit market. Larvae remain
protected for almost their entire development within the mines
limiting the effectiveness of chemical control. There are many
generations per year in different parts of Iran, and typically
5
,6
three to four generations can cause damage to fruit. Insect
pest management, monitoring and control programmes utilising
sex pheromones as behaviour modifying chemicals have
become necessary for several insect groups, particularly moths.
Thus, a pheromone-based method for sampling A. ceratoniae
populations by using traps to catch the adult male moths might
provide a method for timing and so maximising the efficacy of
control.
(
8E,10E)-Tetradecadienal is a sex pheromone component
of Marmara gulosa Guillén and Davis (Lepidoptera:
Gracillariidae), which is a sporadic pest of citrus and a number
of other crops. It was synthesised and used as a reliable and
7
accurate tool for monitoring densities of M. gulosa. The
Z-isomer of the sex pheromone of the female Douglas Fir
Cone Gall Midge, tridecadien-2-yl acetate with non-conjugated
double bonds, was synthesised from a diyene by reduction over
P-2 nickel in good yield. In Douglas Fir seed orchards, sticky
traps baited with 2S-Z4-Z7 captured the male Contarinia
8
oregonensis (Diptera: Cecidomyiidae). Reduction of an alkyne
stereoselectively to the cis or trans isomer is always a challenge
in sex pheromone synthesis, and many reactions have been
examined. In this regard, (Z,Z)-9,11-tetradecadienyl acetate, as
a minor component of the sex pheromone gland of the Egyptian
Cotton Leaf Worm, was stereoselectively reduced to the (Z,Z)-
9
conjugated diene by Zn(Cu/Ag)/MeOH/H2.
Three pheromone components including (Z,E)-9,11,13-
tetradecatrienal, (Z,E)-9,11-tetradecadienal and (Z)-9-
tetradecenal of A. ceratoniae were extracted by solvent. The
first component, which was mentioned above, is quite active
in attracting males in biological assays and field tests by itself.
Fig. 1 Synthesis of (Z,E)-9,11,13-tetradecatrienal.
*
Correspondent. E-mail: zjnpr@zjut.edu.cn

2
00 JOURNAL OF CHEMICAL RESEARCH 2017
Results and discussion
-Decyn-1-ol was prepared from 3-decyn-l-ol in 85% yield via
reaction with lithium amide to rearrange the alkyne bond to
various mobile phases. The elemental analysis was performed with an
Elementar Analysensystem GmbH Vario EL CHNS mode, which were
within ±0.4% of theoretical values for C, H, and N.
9
12
the terminal position. The intermediate terminal alkyne was
(E)-1-Chloro-dodec-l-en-3-yn-12-ol (1)
then coupled with E-l,2-dichloroethylene to afford the alcohol
A dry 50 mL flask was loaded with bis(triphenylphosphine)
palladium(II) chloride (300 mg, 0.45 mmol) and CuI (160 mg,
0.8 mmol) and flushed with argon. 9-Decyn-1-ol (1 g, 7.5 mmol)
which was prepared by zipper reaction from 3-decyn-1-ol, trans-1,2-
dichloroethylene (0.13 mL, 1.7 mmol), and THF (3 mL) were added to
the reaction flask. Diisopropylamine (0.18 mL, 1.3 mmol) was then
added dropwise to the stirred mixture, and the initially pale yellow
solution rapidly turned into brown and then black. The mixture was
stirred at room temperature for 1 day. Hexane (20 mL) was then added,
and the mixture was filtered. The filtrate was extracted by saturated
1
, using a (Ph P) PdCl catalyst, and THF as the solvent.
3 2 2
A slurry of 9-decyn-1-ol (1 equiv.), E-l,2-dichloroethylene
13
(
2.5 equiv.), (Ph P) PdCl (0.035 equiv.), CuI (0.13 equiv.) and
3
2
2
diisopropylamine (2 equiv.) in THF, was stirred at 25 ºC for
4 h, to give the chloroalcohol 1 in 89% yield. Compound 1 was
not protected as the THP ether and directly reacted with 2 equiv.
2
11
vinylmagnesium bromides in toluene, with (Ph P) Pd catalyst ,
3
4
yielding 2 in 84% isolated yield. In this study, it was found that
the reduction of 2 proceeded at a satisfactory rate in THF: water
aqueous NH Cl (2 × 3 mL), dried and passed through a column of
(
8:2) at room temperature, using zinc granules activated simply
4
silica gel, and eluted with 20% EtOAc in hexane. The eluate was
by stirring with dilute HCl. Alcohol 3 was obtained in good
concentrated, yielding 1.2 g (5.6 mmol) (89% yield) of chloroalcohol
yield with no detectable isomer of the C double bond or the
1
1
1
(
1). HNMR δ: 1.21–1.44 (m, 8H, H7, 8, 9, 10), 1.45–1.6 (m, 5H, H6,
newly formed C double bond. It was stereochemically pure by
9
11, OH), 2.28 (td, 2H, J = 6.8, 2.2 Hz, H5), 3.65 (t, 2H, J = 6.7 Hz,
NMR and GC/MS. The stereochemistry of the new olfin bond
H12), 5.92 (dt, 1H, J = 13.5, 2.3 Hz, H2), 643 (d, 1H, J = 13.5 Hz, H1).
MS m/z: 179 (M-Cl), 114, 105, 91, 79 (100), 67, 55. Anal. calcd for
C H ClO : C, 68.32; H, 9.11; found: C, 68.12; H, 9.32%.
between C –H and C –H was established as the (Z)-isomer on
9
10
1
the basis of the coupling constant J = 10.7 Hz ( H NMR, δ: 5.48
and 6.09) which is lower than (E)-isomer coupling mentioned in
references (J = 15 Hz). This method, as originally reported,
used zinc powder in refluxing aqueous 1-propanol, was further
improved by activating the zinc dust with copper and silver
17
27
2
13,14
11(E),13-Tetradecadien-9-yn-1-ol (2)
Tetrakis (triphenylphosphine) palladium (0.3 g, 0.26 mmol) and
chloride 1 (1.3 g, 4.4 mmol) were added to toluene (10 mL) under N2
15
at room temperature. The mixture was cooled in an ice-bath while
salts. These authors and others also reported that several other
vinyl magnesium bromide (9 mL of a 1 M solution in THF) was added
dropwise over 5 min. The mixture was warmed to room temperature
and stirred overnight. The reaction mixture was poured into hexane
methods (Lindlar catalyst/H ) for stereo- and regioselectively
2
reducing the conjugated dienynes 2 were not satisfactory, giving
mixtures of products. Alcohol 3 was obtained in good yield
with no detectable isomerisation of either the C double bond
(
30 mL), extracted thoroughly with 2 M NH Cl and brine, dried, and
4
1
1
concentrated under vacuum, to give the dienynol 2 as a yellow oil
or the newly formed C double bond. However, Millar (1990)
9
1
(
0.72 g, 3.4 mmol) 79% yield. HNMR δ: 1.24–1.46 (m, 8H, H3, 4, 5,
reported that the product was contaminated by about 6% of an
unidentified rearrangement product, which was removed by
recrystallisaing the p-nitrobenzoate derivative of 3. But, in our
case, we could not separate these contaminants by crystallisation
in toluene at –20 °C. Purity of compound 3 is very important for
biological activity. In other words, the reduction of alkyne by
Pd/BaSO and H resulted in alcohol 3 which was followed by
6
3
1
), 1.46–1.65 (m, 5H, H2, 7, OH), 2.33 (td, 2H, J = 6.9, 2.2 Hz, H8),
.65 (t, 2H, J = 6.6 Hz, H1), 5.12 (d, 1H, J = 9.7 Hz, H14), 5.25 (br.d,
H, J = 16.5 Hz, H14), 5.62 (dt, IH, J = 15.6, 2.0 Hz, H11), 6.35 (dt, 1H,
–1
J = 16.5, 10.0 Hz, H13), 6.51 (dd, 1H, J = 10.9, 15.4 Hz). IR cm : 3333
+
(s, br.), 2932 (s). MS m/z: 206 (M ), 105, 91 (100), 79, 65, 41. Anal.
calcd for C H O: C, 80.50; H, 10.75; found: C, 80.77; H, 10.86%.
14
22
4
2
(
Z,E)-9,11,13-Tetradecatrienol (3)
Zinc dust (2.39 g, 46.50 mmol) was stirred three times with HCl (3%)
6 mL) for 2 min under argon. The acid was decanted and the zinc
oxidation. The trienal was ineffective in biological activity. The
synthesis was completed by oxidation of the alcohol 3 to the
target aldehyde. A pyridinium chlorochromate/molecular sieve
mixture was used, as had been previously reported. The product
was kept at –20 °C in a dark place until it was used.
(
was rinsed twice with distilled water and added to a flask containing
THF (8 mL) and H O (2 mL), followed by a solution of the dienynol 2
2
(
2
0.3 g, 1.45 mmol) in THF (1 mL). The mixture was stirred for 72 h at
5 °C under argon, then filtered, and washed with THF (10 mL). The
filtrate was concentrated and residue was extracted with Et O:hexane
Experimental
2
(
Z,E)-9,11,13-Tetradecatrienal was synthesised by a modified Millar
(
1:1), aq. sat. NH Cl, dried over MgSO , and concentrated, and purified
1
4
4
(1990) method (Fig. 1). Tetrahydrofuran (THF) was distilled from
by vacuum flash chromatography on silica gel (hexane/EtOAc, 95:5)
the sodium/benzophenone ketyl under N . Extracts were dried over
2
giving the olefin 3 as a colourless oil (0.32 g, 1.45 mmol, quantitative
anhydrous Na SO , and concentrated with a rotary evaporator under
2
4
1
yield). HNMR δ: 1.2–1.45 (m, 8H, H3, 4, 5, 6), 1.5–1.65 (m, 4H, H2,
reduced pressure. Crude products were purified by flash or vacuum
flash chromatography on silica gel (230–400 mesh). Reactions with air
or water sensitive reagents were carried out in dried glassware under N2
7
), 2.19 (br. quartet, 2H, J = 6.8 Hz, H8), 2.37 (s, lH, OH), 3.64 (t, 2H,
J = 6.6 Hz, Hl), 5.08 (d, lH, J = 10.2 Hz, H14), 5.21 (d, lH, J = 15.6 Hz,
Hl4’), 5.48 (dt, lH, J = 10.7, 7.7 Hz, H9), 6.02 (br. t, lH, J = 11.0 Hz,
H10), 6.20 (dd, lH, J = 14.9, 10.7 Hz, H12), 6.41 (dt, lH, J = 16.8, 10.3
atmosphere. All samples were analysed by GC/MS on a fused capillary
column HP5-MS (30 m length, 0.25 mm I.D., 0.25 mm film thickness,
Agilent) in an Agilent. 6890 chromatograph equipped with the mass
selective detector Agilent 5973 in the following conditions: the injector
–1
Hz, H13), 6.51 (dd, lH, J = 14.8, 11.3 Hz, H11). IR cm : 3345 (s), 2940
+
(
s), 1005 (s). MS m/z: 208 (M ), 107, 91, 79 (100), 67. Anal. calcd for
C H O: C, 80.71; H, 11.61; found: C, 80.87; H, 11.53%.
–1
14 24
temperature was held at 250 °C; He as carrier gas at l mL min ; oven
temperature programme, 5 min isotherm at 45 °C followed by linear
(Z,E)-9,11,13-Tetradecatrienal
–1
temperature increase of 4º C min up to 300 °C held for 10 min. All
The trienol 3 was converted to corresponding aldehyde by pyridinium
14
chemicals and reagents were obtained from Merck and Sigma-Aldrich.
chlorochromate (PCC) oxidation. CH Cl (10 mL) and PCC (0.36 g,
2 2
1
H NMR spectra were measured using a Bruker 500 MHz spectrometer
1.68 mmol) and powdered molecular sieve were placed in a flask.
(
Brucker, Rheinstetten, Germany). Chemical shifts were expressed as
Alcohol 3 (0.18 g, 0.84 mmol) in CH Cl (2 mL) was added to this
2
2
δ (ppm) with tetramethylsilane as internal standard. The infrared (IR)
spectra were obtained on a Shimadzu IR prestige-21. The purity of all
compounds was confirmed by thin-layer chromatography (TLC) using
solution, and the mixture was stirred for 6 h. Hexane was then added,
and the mixture was stirred for 10 min and then filtered. The filtrate
was dried, concentrated, and then flash chromatographed (SiO ),
2

JOURNAL OF CHEMICAL RESEARCH 2017 201
to give 9(Z),11(E),13-tetradecatrienal as a colourless oil (0.14 g,
3
4
A.A. Cosse, J.J. Endris, J.G. Millar and T.C. Baker, Entomol. Exp. Appl.,
1994, 72, 233.
R.L. Warner, Contributions to the biology and the management of the
carob moth, Ectomyelois ceratoniae (Zeller) in ‘Deglet Noor’ date
gardens in the Coachella Valley of California. PhD dissertation, California
Riverside, CA, 1988, p. 260.
1
0
5
2
.7 mmol, 83%). H NMR (500 MHz, CDCl ) δ: 1.24–1.31 (m, 8H, H4,
, 6, 7), 1.55–1.62 (m, 2H, H3), 2.18 (brq, 2H, J = 6.8 Hz, H8), 2.42 (td,
H, J = 7.0, 2.0 Hz, H2), 5.09 (d, 1H, J = 10.0 Hz, H14), 5.22 (d, 1H,
3
J = 16.8 Hz, H14`), 5.47 (dt, 1H, J = 10.8, 7.6 Hz, H9), 6.02 (brt, 1H,
J = 10.8 Hz, H10), 6.20 (dd, 1H, J = 15.2, 10.8 Hz, H12), 6.41 (dt, 1H,
J = 16.8, 10.4 Hz, H13), 6.41 (dt, 1H, J = 16.8, 10.4 Hz, H13), 6.50 (dd,
5
6
M. Shakeri, Appl. Ent. Phytopath., 1993, 60, 29.
F. Mozaffarian, A. Sarafrazi and G. Nouri Ganbalani, J. Insect. Sci., 2007,
–
1
1
3
2
H, J = 15.2, 11.6 Hz, H11), 9.78 (t, 1H, J = 2 Hz, aldehyde H). IR cm :
7, 1536.
040 (w), 2940 (s), 2747 (m), 1730 (s), 1008 (s), 945 (m). MS m/z: 207,
06 (M ), 178, 135, 121, 107, 94, 93, 91, 79 (100), 77, 67, 41. Anal. calcd
+
7
8
9
J.S. Mcelfresh, J.A. Moreira, E.E. Grafton-Cardwell, D.H. Headrick. J.M.
Heraty, M. Guille and J.G. Millar, J. Econ. Entomol., 2009, 102, 574.
R. Gries, G. Khaskin, G. Gries, R.G. Bennett, G.G. Skip King, P. Morewood,
K.N. Slessor and W.D. Morewood, J. Chem. Ecol., 2002, 28, 2283.
I. Navarro, E. Mas, G. Fabrias and F. Camps, Biol. Med. Chem., 1997, 5,
for C H O: C, 81.50; H, 10.75; found: C, 81.66; H, 10.56%.
14
22
Acknowledgment
We are grateful for the financial support of the Iranian Research
Institute of Plant Protection.
1267.
10
T.C, Baker, W. Francke, J.G. Millar, C. Lofstedt, B. Hansson, J.W. Du, P.L.
Phelan, R.S. Vetter, R. Youngman and J.L. Todd, J. Chem. Ecol., 1991, 17,
Received 7 January 2017; accepted 18 February 2017
Paper 1704520
https://doi.org/10.3184/174751917X14894997017450
Published online: 28 March 2017
1973.
11 J.L. Todd, J.G. Miller, R.S. Vetter and T.C. Baker, J. Chem. Ecol., 1992,
18, 2331.
12 S.R. Abrahams and A. Shaw, Org. Syn., 1988, 66, 127.
1
3 Y.M.A. Mohamed and T.V. Hansen, Tetrahedron, 2013, 69, 3872.
References
14 I. Nevarro, E. Mas, G. Fabri and F. Camps, Biol. Med. Chem., 1997, 5, 1267.
15 W. Boland, N. Schroer and C. Sieler, Helv. Chim. Acta., 1987, 70, 1025.
16 A.J. Moreira, S.J. Mcelfresh and J. Millar, J. Chem. Ecol., 2006, 32, 169.
1
2
J.G. Millar, Agric. Biol. Chem., 1990, 54, 2473.
S. Gothilf, Phytoparasitica., 1984, 12, 77.