Synthesis of E-9-dodecen-1-yl acetate using organomanganese reagents

Article abstract of DOI:10.1515/znb-2000-0705

The Grignard reagent obtained from 2-(6-bromohexyloxy)-tetrahydropyrane, by treatment with anhydrous manganese(II) chloride was transformed to the corresponding organomanganese reagent, which was coupled with E-1-bromo-3-hexene by treatment with anhydrous manganese chloride. Further deprotection and acetylation furnished E-9-dodecen-1-yl acetate. A second procedure involved the coupling of E-3-hexenylmanganese bromide and 6-bromohexyl acetate. Coupling reactions were carried out at 0 °C, using tetrahydrofurane and N-methylpyrrolidone as co-solvent.

Full text of DOI:10.1515/znb-2000-0705

Synthesis of E-9-Dodecen-l-yl Acetate Using Organomanganese Reagents
J. Belmar3, J. Téllezb, J. Baezab, and J. Freerb
a Department of Organic Chemistry and b Laboratory of Renewable Resources, Faculty of
Chemical Sciences, Universidad de Concepcion, Casilla 3-C, Concepcion, Chile
Reprint requests to Dr. Julio Belmar. Fax: 56-41-245974. E-mail: jbelmar@udec.cl
Z. Naturforsch. 55 b, 583-586 (2000); received February 1, 2000
Pheromone, Organomanganese, E-9-Dodecen-l-yl Acetate
The Grignard reagent obtained from 2-(6-bromohexyloxy)-tetrahydropyrane, by treatment
with anhydrous manganese(II) chloride was transformed to the corresponding organomanganese
reagent, which was coupled with E-l-bromo-3-hexeneby treatment with anhydrous manganese
chloride. Further deprotection and acetylation furnished E-9-dodecen-l-yl acetate. A second
procedure involved the coupling of E-3-hexenylmanganese bromide and 6-bromohexyl acetate.
Coupling reactions were carried out at 0 C, using tetrahydrofurane and N-methylpyrrolidone
as co-solvent.
Introduction
became the triphenylphosphine oxide that is ob­
tained as a by­product and renders the purification
of the target compound more difficult, and the pres­
ence of some Z­isomer that makes the mixture un­
suitable for biological purposes [4].
Coupling reactions using organomanganese(II)
reagents reported in recent years [5­7] show high
yields with temperature conditions which are easily
achievable. This result prompted us to try such kind
of reagents to synthesize E­9­dodecen­l­yl acetate
and the results are here reported.
In Chile the pine shoot moth (Rhyacionia buo-
liana) was first detected in 1985, since then the
population of this insect has spread out in such an
extent that it has become the main forest pest in our
country. Nowadays it covers about 90% of the pine
planted area. There are 1,380,000 hectares planted
with pine that account for 75% of the forest plan­
tations. Productivity losses up to 15% of the total
amount of wood at the moment of harvesting have
been measured. These losses are due to the tree mal­
formation that result as a consequence of the insect
attack.
Results and Discussion
We are currently studying the potential of using
The first route is outlined in Scheme 1. E ­l­
the sex pheromone to control the pine shoot moth bromo­3­hexene (2) was prepared from commercial
and in this context it is interesting to study new E­3­hexen­l­ol (1) that was added to freshly pre­
methods to obtain its components: E­9­dodecen­ pared dibromotriphenylphosphorane. On the other
yl acetate and E­9­dodecen­l­ol [1]. Since these side, monobromination of 1,6­hexanediol (3) with
chemicals are imported and very expensive, we are 47% aqueous HBr afforded 6­bromo­hexan­l­ol (4)
interested in reactions that would allow obtaining that was protected by preparing the tetrahydropy­
big amounts of them. Our future goal is a pilot plant ranyl ether (5). Compound 5 was used to pre­
scale. Classical methods to carry out the synthe­ pare the Grignard reagent (6), which by addition
sis of compounds like E­9­dodecen­l­yl acetate are of anhydrous manganese(II) chloride was trans­
the acetylenic route [2] and the Wittig reaction [3]. formed to the organomanganese reagent (7). Cou­
The first one seems to be the best suited for large­ pling of 7 with E­ l­bromo­3­hexene in the presence
scale synthesis, however, in order to achieve very of CuCl2 and LiCl as catalysts and NMP as co­
high yields, hexamethylphosphoryltriamide must be solvent, yielded compound 8 that was hydrolyzed
used as a co­solvent. This chemical is very toxic and and then acetylated to obtain E­9­dodecen­l­yl ac­
expensive. The second drawback of this reaction etate (10).
is that very low temperature is required, ­78 and
It is also reported [61 that organomanganese(II)
­
30 °C. In the Wittig reaction, the main problems reagents do not react with acetates. Therefore we
0
932-0776/00/0700-0583 $ 06.00 © 2000 Verlag der Zeitschrift für Naturforschung, Tübingen • www.znaturforsch.com
K
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 6/24/15 4:10 PM

5
84
J. Belmar et al. ■A New Synthesis of E-9-Dodecen-l-yl Acetate
decided to try the synthesis of E­9­dodecen­l­yl E­9­dodecen­l­ol is the second pheromone compo­
acetate following the route outlined in Scheme 2. nent [1] in/?, buoliana. The starting E­3­hexen­l­ol
By this method the use of expensive dihydropy­ used was commercially available, but it can also be
rane could be avoided and replaced by acetic an­ prepared as described in the literature [8].
hydride. Treatment of 6­bromo­hexan­1­ol (4) with
Experimental
acetic anhydride afforded the acetate 11, subsequent
coupling with E­3­hexenyl manganese bromide (13)
gave 10. This order was followed because 6­bromo­
The compounds were characterized using ’H, i3C
NMR spectroscopy (Bruker AC 250P; 62.9 and 250 MHz,
hexyl acetate does not form a Grignard reagent and
respectively). In all the cases the solvent was deuteriated
therefore no organomanganese derivative can be ob­ chloroform.
tained from it.
Synthesis of E-l-bromo-3-hexene (2)
The routes described are characterized by very
high yields, however, the second one seems more
interesting to us, because the acetate is immediately
obtained and with fewer steps. Although some ac­
In a two necked flask fitted with a reflux condenser
with a CaCb tube on top) and a dropping funnel, triph-
(
enylphospine (230.0 g; 0.88 mole) is dissolved in methy-
etate hydrolysis was observed, this is not a big prob­ lene chloride. The solution is cooled to 0 °C and more
lem because the alcohol and the acetate can readily
be separated through a silica column. Furthermore,
solvent is added if some crystallization is observed. To
the stirred solution, bromine (40.98 ml, 0.80 mole) is
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 6/24/15 4:10 PM

J. Belmar et al. • A New Synthesis of E-9-Dodecen-l-yl Acetate
585
the solvent is removed in a rotatory evaporator and the
crude distilled in a water pump vacuum. The fraction col-
lected between 75 - 80 °C is 6-bromohexan-l-ol. Yield
6
5% (100 g).
H NMR: 3.59 (t, 2H, CH20-), 3.45 (s, 1H, OH), 3.40
t, 6.3 Hz, 2H, CH2Br), 1.87 (q, 2H, CH2), 1.62-1.30 (m,
m, 6H, 7.5 Hz, 3CH2).
3C NMR: 62.1 (1C, CH2OH), 33.6, 32.5, 32.1, 27.7,
4.7 (5C, CH2).
‘
(
1
2
Synthesis of2-(6-bromohexyloxy)tetrahydropymne (5)
A mixture of 6-bromohexan-1-ol (10 g, 0,07 mole) and
dihydropyrane (6.47 g, 0.77 mole) and some drops of tri-
fluoroacetic acid are stirred for 12 h at r. t.. The solution
is washed with saturated aqueous sodium carbonate, and
then with water until pH 7. The organic phase is dried over
sodium sulfate and filtered. The filtrate is concentred in a
rotatory evaporator to eliminate the unreacted dihydropy-
rane. At this stage the yield is 85%. This product is used
in the next step without further purification.
1
3C NMR: 98,6 (C-l, acetal), 67.2, 62.6 (2C, CH20),
CUOI2
3
3.6, 32.5, 30.7, 29.3, 27.8, 25.3, 19.5 (8C, 8CH2).
LiCI / NMP
10
Synthesis of E-2-(9-dodecenyloxy)tetrahydropyrane (8)
dropped. A pale yellow precipitate appears at the end of
the addition. Stirring is continued while allowing the mix-
ture to warm up to r. t., and then E-3-hexen-l-ol (50.0 g,
This reaction is carried out under nitrogen atmosphere.
To a three necked flask containing magnesium turnings
(
5
24.3 g, 0.05 mole) and sodium dried THF, a solution of
(7.39 g, 0.045 mole) in 15 ml of THF is added drop-
0
.5 mole) is added dropwise. The solid material dissolves
and stirring is continued for 12 h. The solution is then
saturated with pentane to precipitate any unreacted phos-
phorane and triphenylphosphine, and then filtered. The
solution is washed with aqueous 10% NaHC03 and then
with methanol containing 10% of water to eliminate the
remaining triphenylphosphine oxide. The hexane phase
is dried over sodium sulfate. After filtering, the solvent
is removed by normal distillation. The remaining crude
is distilled with water pump vacuum and the fraction be-
tween 73 - 76 °C collected. Yield 89% (67 g).
wise. Starting of the reaction is promoted by adding some
drops of 1,2-dibromoethane. After the metal is dissolved,
stirring is continued for 30 min. The solution is cooled
to 0 °C and anhydrous manganese(II) chloride (5.91 g,
0
.047 mole) dissolved in THF (15 ml) is added at once.
The mixture is stirred for 12 h at r. t. and then bromide 2
6.11 g, 0.038 mole) and 35 ml of NMP are added together
with a solution of CuCl2 (0.28 g) and LiCI (0.17 g) in THF
20 ml). The solution is stirred for 6 h. The reaction is
(
(
quenched adding water and neutralized with 10% aque-
ous HC1. THF evaporated in a rotatory evaporator and the
remaining mixture is extracted three times with hexane.
The collected organic extracts are dried with sodium sul-
fate and filtered. The solvent is evaporated and the product
chromatographed on a silica gel column (hexane : ethyl
ether, 90 : 10). Yield: 70% (6 g).
’
H NMR: 5.5 (m, m, 2H, =CH), 3.99 (t, 2H, 6.3
Hz, CH2Br), 2.59 (m, 2H, C //2CH2Br), 2.07 (m, 2H,
CH2CH3), 1.05 (t, 3H, 8.6 Hz, CH3).
1
3C NMR: 135.4 (1C, C-3), 125.4 (1C, C-4), 36.0,32.9
(
2C, C-3 and C-4), 25.5 (1C, C-l), 13.6 (1C, C-6).
Synthesis of 6-bromohexan-1-ol (4)
1
3C NMR: 131.3, 129.2 (2C, =CH), 98.8 (1C, acetal
CH), 67.3 62.3 (2C, CH20), 33.7, 32.7, 31.5, 30.7, 29.5,
8.0, 25.4, 22.57, 19.63 (10C, CH2), 14.0 (1C, Me).
In a flask provided with a reflux condenser and a
mechanical stirrer, a mixture of 1,6-hexanediol (100 g;
2
0
.85 mole), 46% aqueous HBr (600 ml; 5.08 mole) and
hexane (300 ml) is heated to reflux for 2 h. The mixture is
allowed to cool down to r. t. and the phases are separated.
The aqueous phase is neutralized with solid NaHC03 and
extracted three times with ether. The collected organic
extracts are dried with sodium sulfate. After filtering,
Synthesis of E-9-dodecen-1 -ol (9)
Compound 8 (5.0 g, 0.019 mole) is dissolved in
methanol (10 ml). A few of trifluoroacetic acid are added
and the solution is stirred at r. t. and then concentrated in a
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 6/24/15 4:10 PM

5
86
J. Belmar et al. • A New Synthesis of E-9-Dodecen-l-yl Acetate
rotatory evaporator and diluted with ether. The new solu-
tion is washed three times with saturated aqueous sodium
bicarbonate and then with saturated acqueous NaCl until
pH 7. The organic phase is dried with sodium sulfate and
filtered, and the solvent is evaporated. The crude is chro-
matographed on a silica column (hexane : ethyl ether, 90
anhydride and 100 ml of pyridine and a small ammount
of dimethylamino- pyridine are used. Yield 98% (5.8 g).
'H NMR: 3.96 (t, 6.6 Hz, 2H, CH20), 3.31 (t, 6.9 Hz
2H, CH2Br), 1.95 (s, 3H, CH3), 1.77 (q, 2H, CH2), 1.35
(m, 4H, 2CH2).
13C NMR: 170.6 (1C, C=0), 64.0 (1C, CH20 ), 33.3,
32.2, 28.1, 27.4, 25.2, 24.8 (5C, CH2), 20.6 (1C, Me).
:
10). Yield 78% (2.7 g).
H NMR: 5.42 (m, 2H, =CH), 3.59 (t, 7.5 Hz, 2H,
CH20), 3.23 (s,lH, OH), 2.01 (m, 4H), 1.54 (m,2H), 1.31
'
Synthesis of E-9-dodecenyl acetate (10)
(
s, broad, 10H), 0.97 (t, 6.8 Hz, 3H, Me).
3C NMR: 131.7, 129.1 (2C, =CH), 62.4 (1C, OCH2),
2.6, 32.4, 29.5, 29.4, 29.3, 29.0, 25.7, 25.4 (8C, CH2),
3.8 (1C, Me).
Route B: This reaction is carried out under nitrogen
atmosphere. To a flask containing magnesium turnings
1
3
1
(
24.31 g, 0.051 mole) and dried THF, E-l-bromo-3-
hexene (7.34 g, 0.045 mole) dissolved in 15 ml of THF
are added dropwise. The mixture is stirred for 6 h after
the magnesium has dissolved. To this flask a solution of
MnCl2 (5.91 g, 0.047 mole) in 15 ml of THF is slowly
dropped keeping the temperature between 0 and 5 °C with
an ice bath. After the addition the solution is for during
12 h and then transferred with a double tipped-needle
to a flask containing 6-bromohexenyl acetate (8.37 g,
0.038 mole) in THF. To the new solution NMP (35 ml)
is added and LiCl (0.11 g) and CuCl2 (0.19 g) in THF
(15 ml) are slowly dropped so that the reaction temper-
ature does not rise. Stirring is continued for 6 h. The
solution is again cooled with an ice bath and the reaction
quenched by adding water and then 10% aqueous HC1
until the pH is neutral. The solvent is evaporated in a
rotatory evaporator. The remaining mixture is extracted
three times with hexane. The collected hexane extracts
are dried over sodium sulfate and filtered, and the solvent
is evaporated. The crude is chromatographed on a silica
column (hexane : ethyl ether, 70 : 30). Yield 57% (4.9 g).
Synthesis of E-9-dodecen-l-yl acetate (10)
Route A: A solution of E-9-dodecen-l-ol 9 (2.5 g,
0
.014 mole), acetic anhydride (10 ml), pyridine (10 ml),
and some crystals of 4-dimethylaminopyridine is stirred
for 12 h at r. t.. The solution is diluted with ether, cooled
with ice, then treated with 10% HC1 until the pH is acid,
and washed with saturated acqueous NaCl until pH 7. The
organic phase is dried over sodium sulfate and filtered, and
the solvent is evaporated. The crude is purified through
a silica column (hexane : ethyl ether, 98 : 2). Yield 94%
(
3 g).
H NMR: 5.42 (m, 2H, =CH), 4.05 (t, 6.3 Hz, 2H,
OCH2), 2.04 (s, 3H, CH3CO), 1.01 (m, 4H, 2CH2), 1.62
m, 2H, CH2), 1.30 (s, broad, 10H, 5CH2), 0.96 (t, 7.5 Hz,
‘
(
3
H, CH3).
13C NMR: 171,1 (1C,C=), 131.9, 129.2 (2C, =CH),
6
2
4.6 (1C, OCH2), 32.5, 29.6, 29.3, 29.2, 29.0, 28.6, 25.9,
5.5 (8C, CH2), 20.9 (1C, CH3CO), 13.9 (1C, CH3).
Synthesis of 6-bromohexyl acetate (11)
Acknowledgements
The same procedure described for 10 is followed. 6-
Bromohexan-l-ol 4 (50 g, 0.383 mole), 100 ml of acetic
The authors thank for financial support from FONDEF
Chile (Grant D97 I 2039).
[
1] M.S. Meyer, J. R. Me. Laughling, CRC Handbook of
Insect Pheromones and Sex Atractants, CRC Press,
Boca Raton, Florida (1991).
[4] T. G. Gray, K. N. Slessor, R. F. Shepherd, G. G.
Grant, J. F. Manville, Can. Ent. 116, 1525 (1984).
[5] G. Cahiez, S. Marquais, Pure Appl. Chem. 68, 53
(1996).
[6] G. Cahiez, Anales de Qufmica 561 (1995).
[7] G. Cahiez, M. Alami, Tetrahedron, 45.4163 (1989).
[8] N. Popovici, A. A. Votar, A. Barabäs, I. Oprean,
F. Hodosan, J. Prakt. Chem. 325, 17 (1983).
[
2] C. A. Hendrick, Tetrahedron 33, 1845 (1987).
3] W. Carruthers, Some Modern Methods of Organic
Synthesis, 3rdEdition, p. 125, Cambridge University
Press, Cambridge, U. K. (1997).
[
Brought to you by | New York University Bobst Library Technical Services
Authenticated
Download Date | 6/24/15 4:10 PM