Ultrasound in fatty acid chemistry: facile dehydrobromination of dibromo fatty esters to acetylenic ester derivatives

Article abstract of DOI:10.1016/S0009-3084(97)00100-X

Dehydrobromination of dibromo derivatives of olefinic fatty acids was accomplished using KOH in 20percent aqueous ethanol under cocomitant ultrasonic irradiation (20 kHz) for 30 min at ambient temperature to give the corresponding acetylenic fatty acid derivatives (52-72percent yield).Ten different dibromo fatty acid substrates were used.Products include: fatty acids with a terminal or internal acetylenic bond; acetylenic fatty acids containing an additional functional group, such as hydroxy, chloro or azide group.The structures of the products were characterized by infrared and NMR spectroscopy. - Keywords: acetylenic fatty esters; dehydrobromination; dibromo fatty esters; ultrasond

Full text of DOI:10.1016/S0009-3084(97)00100-X

Chemistry and Physics of Lipids
91 (1998) 79–83
Ultrasound in fatty acid chemistry: facile dehydrobromination
of dibromo fatty esters to acetylenic ester derivatives
Marcel S.F. Lie Ken Jie *, P. Kalluri
Department of Chemistry, The Uni6ersity of Hong Kong, Pokfulam Road, Hong Kong, People’s Republic of China
Received 8 August 1997; received in revised form 23 October 1997; accepted 23 October 1997
Abstract
Dehydrobromination of dibromo derivatives of olefinic fatty acids was accomplished using KOH in 20% aqueous
ethanol under concomitant ultrasonic irradiation (20 kHz) for 30 min at ambient temperature to give the
corresponding acetylenic fatty acid derivatives (52–72% yield). Ten different dibromo fatty acid substrates were used.
Products include: fatty acids with a terminal or internal acetylenic bond; acetylenic fatty acids containing an
additional functional group, such as hydroxy, chloro or azide group. The structures of the products were
characterized by infrared and NMR spectroscopy. © 1998 Elsevier Science Ireland Ltd.
Keywords: Acetylenic fatty esters; Dehydrobromination; Dibromo fatty esters; Ultrasound
1. Introduction
bromination process was to react the dibromo
fatty acid intermediate with 1,5-diazabicy-
clo(5.4.0)undec-5-ene (DBU) in benzene under
reflux for 5 h. For example, 9-octadecynoic acid
was obtained in 85% yield from methyl 9,10-di-
bromostearate, which was derived from methyl
oleate. But when we repeated the same reaction
under similar conditions as described by Gun-
stone and Hornby, the average yield of 9-octade-
cynoic acid obtained was only 15%. Several
modifications to the procedure were tried to in-
crease the yield of the product. For instance, by
increasing the reflux period of the reaction from 5
to 12 h, the yield was slightly increased to 22%.
One of the most thorough investigations con-
ducted on the chemical transformation of olefinic
fatty acids to the corresponding acetylenic fatty
acids was reported (Gunstone and Hornby, 1969).
Their general procedure involved the bromination
of an olefinic fatty acid to the dibromo intermedi-
ate, which was subsequently dehydrobrominated
in the presence of a base to give the requisite
acetylenic fatty acid. From their result it appeared
that one of the best conditions for the dehydro-
* Corresponding author. Fax: +852 2517 0217.
0009-3084/98/$19.00 © 1998 Elsevier Science Ireland Ltd. All rights reserved.
PII S0009-3084(97)00100-X

80
M.S.F. Lie Ken Jie, P. Kalluri / Chemistry and Physics of Lipids 91 (1998) 79–83
Table 1
Dehydrobromination of dibromo fatty esters with KOH in aqueous ethanol under concomitant ultrasonic irradiation followed by
methylation
Substrate
Reaction time (ultrasound) min
Products
Yield %
CH2BrCHBrꢁR1
30
30
30
30
30
30
30
30
30
30
HCꢀCꢁR1 (1)
62
52
66
72
65
69
55
60
58
65
R2ꢁCHBrCHBrꢁR3
R2ꢁCꢀCꢁR3 (2)
R4ꢁCHOHꢁCH2ꢁCHBrCHBrꢁR3
R5ꢁCHBrCHBrꢁ(CH2)2CHOHꢁR3
R4ꢁCHClꢁCH2ꢁCHBrCHBrꢁR3
R5ꢁCHBrCHBrꢁ(CH2)2CHClꢁR3
R4ꢁCHN3ꢁCH2ꢁCHBrCHBrꢁR3
R5ꢁCHBrCHBrꢁ(CH2)2CHN3ꢁR3
R4ꢁCHOAcꢁCH2ꢁCHBrCHBrꢁR3
R5ꢁCHBrCHBrꢁ(CH2)2CHOAcꢁR3
R4ꢁCHOHꢁCH2ꢁCꢀCꢁR3 (3)
R5ꢁCꢀCꢁ(CH2)2CHOHꢁR3 (4)
R4ꢁCHClꢁCH2ꢁCꢀCꢁR3 (5)
R5ꢁCꢀCꢁ(CH2)2CHClꢁR3 (6)
R4ꢁCHN3ꢁCH2ꢁCꢀCꢁR3 (7)
R5ꢁCꢀCꢁ(CH2)2CHN3ꢁR3 (8)
R4ꢁCHOHꢁCH2ꢁCꢀCꢁR3 (3)
R5ꢁCꢀCꢁ(CH2)2CHOHꢁR3 (4)
R1=(CH2)8COOCH3; R2=CH3(CH2)7; R3=(CH2)7COOCH3; R4=CH3(CH2)5; R5=CH3(CH2)4; OAc=acetoxy.
2. Materials and methods
The use of higher concentrations of DBU than
recommended did not improve the yield (15%)
either. Replacing DBU by sodium hydride as the
base and substituting benzene with dimethyl sul-
foxide as the solvent furnished 9-octadecynoic
acid in 30% yield after 16 h of reflux. Adkins and
Burks recorded a yield of about 40% of 9-octade-
cynoic acid, when 9,10-dibromo-octadecanoic
acid was refluxed with KOH in amyl alcohol for
10 h (Adkins and Burks, 1967).
Many organic reactions carried out under con-
comitant ultrasonic irradiation have shown sig-
nificant increase in the yield of the products
formed. We have recently reported the successful
application of ultrasound energy in the chemical
transformation of long-chain fatty acids and their
derivatives (Lie Ken Jie and Kalluri, 1995, 1996;
Lie Ken Jie and Lam, 1995, 1996; Lie Ken Jie et
al., 1994, 1996, 1997). However, when a mixture
of methyl 9,10-dibromooctadecanoate, DBU and
benzene was irradiated under ultrasound, no
acetylenic derivative was obtained as the starting
material was recovered.
10-Undecenoic acid and oleic acid were pur-
chased from Aldrich Chemical (Milwaukee, WI).
Ricinoleic acid (12-hydroxy-cis-octadecenoic acid)
and iso-ricinoleic acid (9-hydroxy-cis-12-octade-
cenoic acid) were isolated from castor oil and
from the seed oil of Wrightia tinctoria, respec-
tively (Gunstone, 1954). Seeds from Wrightia tinc-
toria were gifts from Prof S.M. Osman,
Department of Chemistry, Aligarh Muslim Uni-
versity, India. The corresponding chloro, azido
and acetoxy derivatives of methyl ricinoleate and
methyl iso-ricinoleate were prepared as described
elsewhere (Lie Ken Jie and Cheng, 1995). Infrared
(IR) and nuclear magnetic resonance (1H and 13C
NMR) spectroscopy were carried out as described
elsewhere (Lie Ken Jie et al., 1994). Ultrasonica-
tion was carried out using a 20 kHz ultrasound
horn (Sonoreactor, Undatim Ultrasonic, Louvain
la Neuve, Belgium) with the reaction mixture
contained in a water-jacketed cell (40 mm i.d., 80
mm length).
In view of our need to obtain acetylenic fatty
acid derivatives for chemical and biological stud-
ies, we describe in this paper a facile and quick
ultrasound-assisted dehydrobromination proce-
dure for long chain olefinic fatty esters to give the
corresponding acetylenic derivatives in good yield
(52–72%). The results of the various reactions are
summarised in Table 1.
2.1. General method for the bromination of
long-chain unsaturated fatty esters with bromine
as exemplified by the bromination of methyl
12-hydroxy-9-cis-octadecenoate
A mixture of methyl 12-hydroxy-9-cis-octade-
cenoate (2.0 g, 6.4 mmol) and diethyl ether (80
ml) was cooled to 0–5oC. A solution of bromine

M.S.F. Lie Ken Jie, P. Kalluri / Chemistry and Physics of Lipids 91 (1998) 79–83
81
(3.0 g in 20 ml of diethyl ether) was added slowly
to the reaction mixture over 10 min and the
reaction mixture stirred for a further 15 min. A
solution of sodium thiosulfate (10%, 20 ml) was
then added to react with the excess bromine. The
ethereal layer was successively washed with water
(2×20 ml) and dried over anhydrous sodium
sulfate. The filtrate was evaporated to give methyl
12-hydroxy-9,10-dibromo-octadecanoate (3.0 g,
99%), which required no further purification.
Methyl 10-undecynoate (1, 62%) IR (film) 3100,
2970, 2850, 2012, 1740, 1440, 1197 and 760 cm−1
;
1H NMR (CDCl3, lH) 1.2–1.6 (m, 12H, CH2),
1.94 (m, 1H, 11-H), 2.17 (t, J=7 Hz, 2H, 9-H),
2.30 (t, J=7.5 Hz, 2H, 2-H) and 3.66 (s, 3H,
COOCH3); 13C NMR (CDCl3, lC) 18.41 (C-9),
24.70 (C-3), 28.49–29.03, 34.07 (C-2), 51.42
(COOCH3), 68.15 (C-11), 84.67 (C-10) and 174.35
(C-1).
Methyl 9-octadecynoate (2, 52% yield) IR(film)
1
2960, 2850, 1740, 1450, 1120 and 740 cm−1; H
NMR (CDCl3, lH) 0.88 (t, J=7 Hz, 3H, CH3),
1.2–1.6 (m, 22H, CH2), 2.13 (t, J=7 Hz. 4H,
8-H, 11-H), 2.34 (t, J=7 Hz, 2H, 2-H) and 3.66
(s, 3H, COOCH3); 13C NMR (CDCl3, lC) 14.13
(C-18), 18.74 (C-8), 18.79 (C-11), 22.72 (C-17),
24.78 (C-3), 28.65–29.74, 31.92 (C-16), 34.12 (C-
2), 51.43 (COOCH3), 80.06 (C-9), 80.37 (C-10)
and 174.33 (C-1).
2.2. General procedure for the
dehydrobromination of long-chain dibromo fatty
esters with KOH in aqueous ethanol under
ultrasonic irradiation as exemplified by the
dehydrobromination of methyl
12-hydroxy-9,10-dibromo-octadecanoate
A mixture of methyl 12-hydroxy-9,10-dibromo-
octadecanoate (3.0 g, 6.4 mmol), ethanol (24 ml),
water (6 ml) and KOH (5.7 g) was placed in a
water-jacketed cell and sonicated for 30 min at
20–25oC. The reaction mixture was acidified with
dilute HCl (6 M, 20 ml) and extracted with diethyl
ether (3×30 ml). The ethereal extract was washed
with water (20 ml) and dried over anhydrous
sodium sulfate. The filtrate was evaporated and
the residue was refluxed with BF3-methanol com-
plex (14%, w/w, 5 ml) and absolute methanol (20
ml) for 15 min. Water (50 ml) was added and the
reaction mixture was extracted with diethyl ether
(3×30 ml). The filtrate was evaporated and silica
column chromatographic separation of the
residue using a mixture of petroleum ether and
diethyl ether (9:1, v/v) as eluent gave pure methyl
12-hydroxy-9-octadecynoate (3, 1.3 g, 66%). IR
Methyl 9-hydroxy-12-octadecynoate (4, 72%
yield) IR 3450, 1740, 1435, 1360 and 1170 cm−1
;
1H NMR (CDCl3, lH) 0.88 (t, J=7 Hz, 3H,
CH3), 1.2–1.6 (m, 20H, CH2), 2.11 (t, J=6 Hz.
2H, 14-H), 2.29 (t, J=6 Hz, 2H, 11-H), 2.33 (t,
J=7 Hz, 2H, 2-H), 3.21 (s, br., 1H, CHꢁOH),
3.66 (s, 3H, COOCH3) and 3.68 (m, 1H, CHOH);
13C NMR (CDCl3, lC) 14.05 (C-18), 15.26 (C-11),
18.77 (C-14), 22.32 (C-17), 24.99 (C-3), 25.67 (C-
7), 28.91–29,58, 31.17 (C-16), 34.07 (C-2), 36.54
(C-10), 37.39 (C-8), 51.41 (COOCH3), 70.72 (C-9,
CHOH), 79.86 (C-12), 80.64 (C-13) and 174.27
(C-1).
Methyl 12-chloro-9-octadecynoate (5, 65%
yield); IR (film) 2960, 2850, 1740, 1450, 1197 and
1
740 cm−1; H NMR (CDCl3, lH) 0.88 (t, J=7
Hz, 3H, CH3), 1.2–1.6 (m, 20H, CH2), 2.12 (m,
4H, 8-H, 11-H), 2.33 (t, J=7 Hz, 2H, 2-H), 3.66
(s, 3H, COOCH3) and 4.12 (quintet, 1H, CHꢁCl);
13C NMR (CDCl3, lC) 14.10 (C-18), 18.72 (C-8),
22.62 (C-17), 24.88 (C-3), 25.62 (C-14), 27.75 (C-
11), 28.65–29.29, 31.81 (C-16), 34.05 (C-2), 36.01
(C-13), 51.46 (COOCH3), 60.19 (C-12, CHꢁCl),
76.30 (C-10), 83.20 (C-9) and 174.28 (C-1).
1
(film) 3450, 1740, 1460, 1360 and 1170 cm−1; H
NMR (CDCl3, lH) 0.88 (t, J=7 Hz, 3H, CH3),
1.2–1.6 (m, 20H, CH2), 2.04 (s, 1H, CHOH), 2.2
(m, 4H, 8-H and 11-H), 2.30 (t, J=7 Hz, 2H,
2-H), 3.66 (s, 3H, COOCH3) and 3.69 (m, 1H,
CHOH); 13C NMR (CDCl3, lC) 14.11 (C-18),
18.72 (C-8), 22.75 (C-17), 24.91 (C-3), 25.66 (C-
14), 27.95 (C-11), 28.75 (C-7), 28.86, 29.15, 31.91
(C-16), 34.02 (C-2), 36.21 (C-13), 51.42
(COOCH3), 70.37 (C-12, CHOH), 78.24 (C-10),
82.41 (C-9) and 174.23 (C-1).
Methyl 9-chloro-12-octadecynoate (6, 69%
yield) IR (film) 2960, 2850, 1740, 1440, 1197 and
1
780 cm−1; H NMR (CDCl3, lH) 0.88 (t, J=7
Hz, 3H, CH3), 1.2–1.8 (m, 20H, CH2), 2.11 (t,
J=6 Hz, 2H, 14-H), 2.33 (t, J=7 Hz, 2H, 2-H),

82
M.S.F. Lie Ken Jie, P. Kalluri / Chemistry and Physics of Lipids 91 (1998) 79–83
2.35 (t, J=6 Hz, 2H, 11-H), 3.66 (s, 3H,
COOCH3) and 4.03 (quintet, 1H, CHꢁCl); 13C
NMR (CDCl3, lC) 14.04 (C-18), 16.31 (C-11),
18.72 (C-14), 22.28 (C-17), 24.93 (C-3), 26.40 (C-
7), 28.78–29.16, 31.11 (C-16), 34.02 (C-2), 37.81
(C-10), 38.35 (C-8), 51.36 (COOCH3), 62.54 (C-9,
CHꢁCl), 78.48 (C-12), 81.07 (C-13) and 174.05
(C-1).
bromination process when benzene was used as
the solvent with DBU. An attempt to use sodium
hydride as the base in dimethyl sulfoxide under
prolonged reflux period (16 h) produced a mar-
ginal increase in the production of the acetylenic
derivative (30%).
Ultrasound energy is best conducted in solvents
such as water and alcohols, due to their polar
properties and high dielectric constants. In view
of the fact that KOH in amyl alcohol was used
(Adkins and Burks, 1967) for the dehydrobromi-
nation of dibromo-octadecanoic acid (in about
40% yield), we decided to reinvestigate this
method under ultrasonic irradiation. The result
under concomitant ultrasonic irradiation (30 min)
at 20–25oC produced only 10% of the requisite
9-octadecynoic acid. Despite the low yield in this
reaction, the result showed that dehydrobromina-
tion could be achieved in a short period (30 min)
of ultrasonication at ambient temperature. Fol-
lowing this lead, a study of mixtures of ethanol
and water was conducted to search for a suitable
solvent system. A serial study of ethanol with
different amounts of water was investigated and it
was found that KOH in 20% aqueous ethanol
provided the optimum condition for the dehydro-
bromination process.
Ten dibromo fatty ester substrates were pre-
pared and subjected to KOH and aqueous ethanol
under concomitant ultrasonic irradiation at 20–
25oC for 30 min. The results are summarised in
Table 1. The yield of these reactions varied from
52 to 72% and the methyl esters of the resulting
acetylenic acids could be readily purified by silica
column chromatography. Terminal and internal
acetylenic products (compounds 1 and 2) could be
prepared by this quick ultrasound procedure.
There was no bond migration of the acetylenic
system as determined by the oxidative cleavage of
the resulting acetylenic fatty esters, which fur-
nished the corresponding mono- and di-acid moi-
eties as determined by gas liquid chromatography
(Lie Ken Jie and Kalluri, 1996).
Methyl 12-azido-9-octadecynoate (7, 55% yield)
IR (film) 2930, 2850, 2099, 1740, 1440, 1249, 1190
1
and 1160 cm−1; H NMR (CDCl3, lH) 0.88 (t,
J=7 Hz, 3H, CH3), 1.2–1.6 (m, 20H, CH2), 2.32
(t, J=7 Hz, 2H, 2-H), 2.40 (m, 4H, 8-H, 11-H),
3.38 (m, 1H, CH-N3) and 3.66 (s, 3H, COOCH3);
13C NMR (CDCl3, lC) 14.10 (C-18), 18.74 (C-8),
22.65 (C-17), 24.96 (C-3), 25.15 (C-14), 25.99 (C-
11), 28.69–29.10, 31.77 (C-16), 33.55 (C-13), 34.03
(C-2), 51.36 (COOCH3), 61.47 (C-12, CHꢁN3),
75.72 (C-10), 82.99 (C-9) and 174.09 (C-1).
Methyl 9-azido-12-octadecynoate (8, 60% yield)
IR (film) 2950, 2850, 2100, 1740, 1440, 1250, 1195
and 760 cm−1 1H NMR (CDCl3, lH) 0.88 (t,
;
J=7 Hz, 3H, CH3), 1.2–1.8 (m, 20H, CH2), 2.12
(m, 4H, 11-H,14-H), 2.33 (t, J=7 Hz, 2H, 2-H),
3.44 (quintet, J=6.5, 2H, CHꢁN3) and 3.66 (s,
3H, COOCH3); 13C NMR (CDCl3, lC) 14.03 (C-
18), 15.85 (C-11), 18.71 (C-14), 22.26 (C-17),
24.92 (C-3), 26.02 (C-7), 28.78–29.23, 31.11 (C-
16), 33.75 (C-10), 34.03 (C-2), 34.30 (C-8), 51.42
(COOCH3), 61.84 (C-9, CH-N3), 78.52 (C-12),
81.32 (C-13) and 174.18 (C-1).
3. Results and discussion
Our effort to repeat the DBU in benzene (Gun-
stone and Hornby, 1969) for the dehydrobromi-
nation of methyl 9,10-dibromo-octadecanoate
resulted in a poor average yield of 15% of the
desired acetylenic product. We are unable to ex-
plain this low yield product formation, but as a
consequence this experience has led us to investi-
gate the use of ultrasound to accelerate the dehy-
drobromination process. After failing to increase
the yield in any significant degree by extending the
reflux period or by increasing the amount of the
base (DBU), it was also discovered that ultra-
sound did not have any effect on the dehydro-
In the case of methyl 12-chloro-9,10-dibromo
and
methyl
9-chloro-12,13-dibromo-octade-
canoate, the dehydrohalogenation process pro-
ceeded exclusively with the elimination of the
bromine atoms as expected, while the chloro atom

M.S.F. Lie Ken Jie, P. Kalluri / Chemistry and Physics of Lipids 91 (1998) 79–83
83
Gunstone, F.D., 1954. The nature of the oxygenated acid
present in Vernonia anthelmintica (Willd) seed oil. J. Chem.
Soc. 1611–1616.
Gunstone, F.D., Hornby, G.M., 1969. The conversion of
alkenoic acids to alkynoic acids by bromination–dehydro-
bromination. Chem. Phys. Lipids 3, 91–97.
Lie Ken Jie, M.S.F., Cheng, K.L., 1995. Nuclear magnetic
resonance spectroscopic analysis of homoallylic and bis
homoallylic substituted methyl fatty ester derivatives.
Lipids 30, 115–120.
Lie Ken Jie, M.S.F., Kalluri, P., 1995. Synthesis of pyrazole
fatty ester derivatives in water: a sonochemical approach.
J. Chem. Soc. Perkin Trans. 1, 1205–1206.
was retained in the products (compounds 5 and
6). This observation was confirmed by the NMR
spectral results. The dehydrobromination of the
azido-dibromo fatty ester substrates proceeded
successfully to give the corresponding azido-
acetylenic fatty esters (compounds 7 and 8). How-
ever, in the case of the acetoxy-dibromo fatty
ester substrates, the presence of the KOH also
caused the acetoxy function to be hydrolysed
which yielded the hydroxy-acetylenic products
(compounds 3 and 4).
Lie Ken Jie, M.S.F., Kalluri, P., 1996. Ultrasound-assisted
oxidative cleavage of acetylenic and ethylenic bonds in
unsaturated fatty esters with potassium permanganate.
Lipids 31, 1299–1301.
Lie Ken Jie, M.S.F., Lam, C.K., 1995. Ultrasound assisted
epoxidation reaction of long chain unsaturated fatty esters
in water. Ultrasonic Sonochem. 2, 11–14.
It can be concluded from these results that
dehydrobromination of dibromo fatty acid deriva-
tives is readily achieved under ultrasound at ambi-
ent temperature when KOH is used as the base in
aqueous ethanol.
Lie Ken Jie, M.S.F., Lam, C.K., 1996. Regiospecific oxidation
of unsaturated fatty esters with palladium(II) chloride-
p-benzoquinone: a sonochemical approach. Chem. Phys.
Lipids 81, 55–61.
Lie Ken Jie, M.S.F., Pasha, M.K., Ahmad, F., 1996. Ultra-
sound-assisted synthesis of santalbic acid and a study of
triacylglycerol species in Santalum album (Linn.) seed oil.
Lipids 31, 1083–1089.
Acknowledgements
The Lipid Research Fund, the Research Grant
Council of Hong Kong, and the Research Grants
Committee of the University of Hong Kong pro-
vided financial assistance.
Lie Ken Jie, M.S.F., Pasha, M.K., Lam, C.K., 1997. Ultra-
sonic stimulated oxidation reactions of 2,5-disubstituted
C18 furanoid fatty esters. Chem. Phys. Lipids 85, 101–106.
Lie Ken Jie, M.S.F., Syed Rahmatullah, M.S.K., Lam, C.K.,
Kalluri, P., 1994. Ultrasound in fatty acid chemistry: syn-
thesis of a novel 1-pyrroline fatty ester isomer from methyl
ricinoleate. Lipids 29, 889–892.
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