A Facile Synthesis of the Sex Pheromone of the Cabbage Looper Trichoplusia ni

Article abstract of DOI:10.1007/s10600-016-1800-7

The sex pheromone of the cabbage looper Trichoplusia ni Hubner, (Z)-7-dodecen-1-yl acetate, was synthesized via a bimolecular nucleophilic substitution reaction between the Grignard reagent of the protected bromohydrin with (Z)-2-hepten-1-yl acetate in the presence of CuI catalyst as a key step. An efficient synthetic method of preparation of the pheromone was achieved from (Z)-2-butene-1,4-diol in four steps with an overall yield of 22.1%.

Full text of DOI:10.1007/s10600-016-1800-7

DOI 10.1007/s10600-016-1800-7
Chemistry of Natural Compounds, Vol. 52, No. 5, September, 2016
A FACILE SYNTHESIS OF THE SEX PHEROMONE
OF THE CABBAGE LOOPER Trichoplusia ni
1
,2*
1
Thanh-Danh Nguyen,
Cong-Hao Nguyen,
2
1*
Chan Im, and Chi-Hien Dang
The sex pheromone of the cabbage looper Trichoplusia ni Hubner, (Z)-7-dodecen-1-yl acetate, was synthesized
via a bimolecular nucleophilic substitution reaction between the Grignard reagent of the protected
bromohydrin with (Z)-2-hepten-1-yl acetate in the presence of CuI catalyst as a key step. An efficient synthetic
method of preparation of the pheromone was achieved from (Z)-2-butene-1,4-diol in four steps with an
overall yield of 22.1%.
Keywords: cabbage looper, Grignard coupling, sex pheromone, Trichoplusia ni Hubner.
The cabbage looper Trichoplusia ni Hubner is a widely distributed polyphagous insect in North America, Africa,
Asia, and parts of Europe. In Vietnam, this pest was found on broccoli, cabbage, tomato, beet, peas, and many weed plants in
the Mekong Delta region [1]. The sex pheromone of Trichoplusia ni [2], (Z)-7-dodecen-1-yl acetate (1), was first isolated and
identified in 1966. Then Green et al. [3] confirmed its attractiveness to male cabbage loopers in field tests. The observed
inhibitory action of the precursor of the pheromone, (Z)-7-dodecen-1-ol (2), due to its pheromonal activity was reported by
Tumlinsonꢀs group [4].
With the aid of the pheromone, effective and cost-efficient control of the insect population can be achieved, hence the
task of synthesizing (Z)-7-dodecen-1-yl acetate. The pheromone was first synthesized by Berger [2] and improved by Green
[
3]. Recently, (Z)-7-dodecen-1-yl acetate was prepared based on co-metathesis of cycloocta-1,5-diene and ethylene [5–7]. The
stereoselective Wittig reaction between 7-hydroxyheptanal and alkylphosphonium salt was employed as a key step in the
synthesis of (Z)-7-alken-1-ol [8, 9]. Oxidation of boronated esters [10, 11] by treatment of trans-1-alkenylborepanes with
iodine in the presence of a base has been explored to afford (Z)-7-alken-1-ol. Fiandanese et al. [12] have used (Z)-1-bromo-2-
phenylthioethene as a reagent containing a double bond, via two cross-coupling reactions with Grignard reagents in the
presence of two catalysts, Pd (II) and Ni (II) complex. The stereoselective reduction of an acetylenic compound as a classical
method has been employed in the synthesis of the pheromone of the cabbage looper [13–16]. However, the drawback of the
above approaches is either obtaining a mixture of E and Z isomer or a difficultly accessible metathesis.
A low-cost method of synthesis is necessary in the practical use of the pheromone to decrease the population of the
insect. In addition, we have successfully employed an efficient synthetic procedure to obtain monoene compounds from
2
-butyn-1,4-diol using the bimolecular nucleophilic substitution reaction between the Grignard reagent and allyl-bearing
variously functional groups [17]. Herein, we describe the development of this method for synthezising the sex pheromone of
Trichoplusia ni Hubner from commercial (Z)-2-butene-1,4-diol using Grignard coupling of the protected bromohydrin in the
presence of CuI catalyst as a key step.
1
) Department of Pharmaceutical Chemistry Technology, Institute of Chemical Technology, Vietnam Academy of
Science and Technology, 1 Mac Dinh Chi Street, District 1, Ho Chi Minh City, Vietnam, e-mail: danh5463bd@yahoo.com;
dangchihien@gmail.com; 2) Department of Chemistry, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701,
Republic of Korea. Published in Khimiya Prirodnykh Soedinenii, No. 5, September–October, 2016, pp. 748–750. Original
article submitted December 9, 2014.
0
0
009-3130/16/5205-0877 2016 Springer Science+Business Media New York
877

O
a
b
c
HO
OH
HO
Cl
O
CH
3
3
4
5
RO
e
O
6
, 2
O
1
6
2
: R = THP
: R = H
d
a. SOCl , reflux, 2h; b. 1. n-PrMgBr, THF, r.t., 2. Ac O, 0°C; c. THPO-(CH ) -MgBr, CuI, THF,
2
2
2 5
0
°C; d. PTSA. MeOH, 50°C; e. Ac O, Py, 0°C
2
Scheme 1
The synthetic pathway is shown in Scheme 1. The (Z)-2-butene-1,4-diol (3) was converted to chlorohydrin4 by treatment
with thionyl chloride in 60.25% yield. After distillation, the intermediate 4 was unstable in light and air, hence it was used for the
next step without further purification. Coupling between the Grignard reagent prepared from 1-bromopropane and compound 4
was carried out at ambient temperature in the absence of catalyst. Acetic anhydride was added into the mixture to afford the ester
5
with a yield of over 70% in two steps following the efficient method devised by Iwamoto et al. [19]. Next, the bimolecular
nucleophilic substitution reaction of the Grignard reagent (prepared from 2-[(5-bromopentyl)oxy]tetrahydro-2H-pyran) with the
acetate 5 in the presence of CuI catalyst followed by de-tetrahydropyranylation with PTSA (p-toluenesulfonic acid) in methanol
at 50ꢁC gave the pheromone inhibitor 2 with a yield of 59.8% in two steps. The residue containing a small amount of by-product
was purified by column chromatography using silica gel impregnated with AgNO (20%, w/w) as the stationary phase [20, 21].
3
The pheromone was prepared by esterification of the alcohol 2 in the presence of pyridine as a catalyst with 86.2% yield. All
products were characterized by FTIR and NMR spectra, which matched those reported previously [5–7].
EXPERIMENTAL
All manipulations were performed under dry nitrogen atmosphere using Schlenk techniques. The starting (Z)-2-butene-
1,4-diol was purchased from Merck (Germany). 2-[(5-Bromopentyl)oxy]tetrahydro-2H-pyran was prepared as in [18].
The other reagents were purchased from Aldrich. THF was dried with Na/benzophenone and freshly distilled prior to use.
The other solvents were purchased from Fluka and used without further purification. Column chromatography was performed
1
with Merck Kieselgel 60. IR spectra were recorded on a Bruker Equinox 55 IR spectrophotometer. H (500 MHz) and
1
3
C (125 MHz) NMR were recorded on a BrukerAvance 500 NMR spectrometer using CDCl as solvent and tetramethylsilane
3
(
TMS) as internal standard. Chemical shifts are reported in ꢂ relative to TMS. GC analyses were carried out using an Agilent
Technologies 6890N chromatograph (USA). Refractive indices (n ) were measured with a WAY-2S ABBE refractometer.
D
(
Z)-7-Dodecenyl acetate (1) was prepared in the manner reported by Bykovꢀs group [6] (yield 86.2%, bp 300.1ꢁC,
1.448). MS m/z 226 (M ). FTIR (KBr, ꢃ , cm ): 2926, 2858, 1738 (s, C=O), 1462, 1372, 1346, 1243, 1180, 1096, 1030,
57, 777, 723. H NMR (500 MHz, CDCl , ꢂ, ppm, J/Hz): 0.90 (3H, t, J = 7.0), 1.23–1.38 (10H, m), 1.64 (2H, m), 2.03
4H, m), 2.04 (3H, s), 4.06 (2H, t, J = 6.5), 5.36 (2H, m). C NMR (125 MHz, CDCl , ꢂ, ppm): 14.10, 21.02, 22.66, 25.86,
2
8
+
–1
n
8
(
D
max
1
3
1
3
3
2
7.10, 27.25, 28.89, 29.65, 29.71, 32.00, 64.66, 129.61, 130.13, 171.22.
Z)-7-Dodecen-1-ol (2) was synthesized as follows: the Grignard reagent solution obtained from 2-[(5-bromopentyl)-
(
oxy]tetrahydro-2H-pyran (6.82 g, 0.027 mol) and magnesium (1.0 g, 0.041 mol) in anhydrous THF (30 mL) was slowly added
dropwise using a syringe to a solution of compound 5 (3.12 g, 0.02 mol) in THF (30 mL) containing a catalytic amount of CuI
(
0.5 g, 2.5 mmol) at 0ꢁC. After stirring overnight at ambient temperature, the mixture was poured into an aqueous solution of
NH Cl and extracted with diethyl ether. The organic layer was washed with an aqueous solution of NaHCO , water, and brine,
4
3
then dried with anhydrous MgSO and concentrated under reduced pressure to afford 8.2 g of the crude product. A mixture of
4
the crude product, PTSA (300 mg), and methanol (200 mL) was stirred at 50ꢁC for 2 h. The mixture was then concentrated to
half volume and poured into the NaHCO solution, and the product was extracted with diethyl ether. The combined organic
3
layers were washed with brine and dried (MgSO ), and the solvent was evaporated. The product was purified on a column of
4
silica gel impregnated with AgNO (20%, w/w) using hexane–EtOAc (ꢄ = 5:1) to afford (Z)-7-dodecen-1-ol (2.20 g, 59.8%
3
r
2
8
+
–1
yield in two steps, bp 270.1ꢁC, n 1.456). MS m/z 184 (M ). FTIR (KBr, ꢃ , cm ): 3339 (br., OH), 2926, 2856, 1462, 1377,
D
max
1
1
125, 1125, 1056, 817, 727, 685. H NMR (500 MHz, CDCl , ꢂ, ppm, J/Hz): 0.90 (3H, t, J = 7.0), 1.20–1.41 (10H, m), 1.59
3
878

(
2H, m), 2.02 (4H, m), 3.64 (2H, t, J = 6.5), 5.35 (2H, m). 13C NMR (125 MHz, CDCl , ꢂ, ppm): 13.96, 22.34, 25.65, 26.92,
3
2
7.12, 29.06, 29.70, 31.96, 32.78, 63.05, 129.70, 130.02.
Z)-4-Chloro-2-buten-1-ol (4) was synthesized as follows: to a three-necked 250 mL round-bottomed flask, equipped
with a magnetic stirrer and a reflux condenser and containing (Z)-2-butene-1,4-diol (3, 26.40 g, 0.30 mol), was slowly added
5.5 mL (41.65 g, 0.35 mol) thionyl chloride dropwise using a syringe. The reaction mixture was refluxed for 2 h. The unreacted
(
2
SOCl was removed under vacuum for 2 h. Then benzene (50 mL) was added, and the solvent was evaporated under reduced
2
pressure on a rotary evaporator to remove sulfur dioxide. The residue was distilled to give 16.15 g of (Z)-4-chloro-2-buten-1-ol
(
60.25% yield), bp 65–75ꢁC (5 mm Hg). The product 4 is unstable in light and air and used without further purification.
Z)-2-Heptenyl acetate (5) was synthesized as follows: the Grignard reagent solution obtained from n-propyl bromide
15.87, 0.13 mol) and magnesium (3.35 g, 0.14 mol) in anhydrous THF (100 mL) was slowly added dropwise using a syringe
(
(
to a solution of (4) (9.2 g, 0.086 mol) in THF (30 mL) at 20ꢁC. Then the mixture was stirred at ambient temperature for 6 h
monitored by GC). After cooling to 0–5ꢁC, acetic anhydride (13.80 g, 0.135 mol) in THF (10 mL) was added dropwise, and the
(
mixture was stirred overnight at ambient temperature. The reaction mixture was poured into an aqueous solution of NH Cl, and
4
the product was extracted with diethyl ether. The combined organic layers were washed with an aqueous solution of NaHCO3,
water, and brine, dried with anhydrous MgSO , and concentrated under reduced pressure. The residue was purified on a column
4
2
8
+
of silica gel using hexane–EtOAc (ꢄ = 10:1) to afford 5 (6.5 g, 71.25%; bp 195.9ꢁC, n 1.436). MS m/z 156 (M ). FTIR (KBr,
ꢃmax, cm ): 3076, 3022, 2958, 2928, 2859, 1742 (s, C=O), 1461, 1373, 1232, 1026, 969, 916, 840, 729, 644, 606. H NMR
r
D
–
1
1
(
500 MHz, CDCl , ꢂ, ppm, J/Hz): 0.92 (3H, t, J = 7.5), 1.26–1.39 (4H, m), 2.06 (3H, s), 2.13 (2H, m), 4.63 (2H, d, J = 7.0), 5.55
3
13
(1H, m), 5.67 (1H, m). C NMR (125 MHz, CDCl , ꢂ, ppm): 13.88, 20.99, 22.24, 27.24, 31.59, 60.42, 123.29, 135.46, 171.00.
3
This work demonstrates a simple and efficient synthetic route for obtaining the sex pheromone of the cabbage looper.
The pheromone was synthesized with an overall yield of 22.1% calculated on the starting (Z)-2-butene-1,4-diol via four
steps. These results contribute to the methodology to further advance the practical use of pheromones as environmentally benign
tools for pest control.
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