Synthesis and characterization of highly functionalized symmetric aromatic hexa-ol intermediates from oleic acid

Article abstract of DOI:10.1016/j.chemphyslip.2008.06.005

A novel highly functionalized aromatic hexa-ol was synthesized by palladium-catalyzed cyclotrimerization of an alkyne fatty acid ester followed by LAH reduction. This polyol product is a novel monomer made from a renewable lipid raw material for the production of polyurethanes, polyesters and polyamides.

Full text of DOI:10.1016/j.chemphyslip.2008.06.005

Chemistry and Physics of Lipids 155 (2008) 43–47
Contents lists available at ScienceDirect
Chemistry and Physics of Lipids
journal homepage: www.elsevier.com/locate/chemphyslip
Synthesis and characterization of highly functionalized symmetric aromatic
hexa-ol intermediates from oleic acid
Dong Song, Suresh S. Narine∗
Alberta Lipid Utilization Program, Department of Agricultural Food and Nutritional Science, 4-10 Agriculture/Forestry Centre, University of Alberta,
Edmonton, Alberta T6G 2P5, Canada
a r t i c l e i n f o
a b s t r a c t
Article history:
A novel highly functionalized aromatic hexa-ol was synthesized by palladium-catalyzed cyclotrimeriza-
tion of an alkyne fatty acid ester followed by LAH reduction. This polyol product is a novel monomer made
from a renewable lipid raw material for the production of polyurethanes, polyesters and polyamides.
© 2008 Elsevier Ireland Ltd. All rights reserved.
Received 18 April 2008
Received in revised form 16 June 2008
Accepted 20 June 2008
Available online 3 July 2008
Keywords:
Aromatic hexa-ol
Cyclotrimerization
Fatty acid alkyne
Dehydrobromination
Unsaturated-␣,␻-dicarboxylic acid
1. Introduction
etable oils (Narine et al., 2007), which were then used to synthesize
polyurethane elastomers and foams (Kong and Narine, 2007; Kong
Oleochemistry has attracted significant interest in the chem-
istry community since oils and fats are renewable, abundant and
environmentally friendly. Through chemical modification, oleo-
chemical feedstocks are converted into a wide range of products,
such as soaps, lubricants, food additives, etc. In the 1980s, oleo-
chemical reactions were mainly focused on the carboxyl group
of fatty acids (Baumann et al., 1988) for example hydrolysis of
fats to make soaps (Sonntag, 1982) and synthesis of fatty amines
from fatty acids (Billenstein and Blaschke, 1984). Recently, signifi-
cantly more interest has been focussed on the hydrocarbon chains
of fatty acids, especially the alkene moiety of unsaturated fatty
acids (Biermann and Metzger, 2004). A large number of novel fatty
compounds have been synthesized through modification of these
carbon–carbon double bonds. Aliphatic polyols are one of the most
successful class of products to derive from such efforts. Epoxida-
tion of alkenes in unsaturated fatty acids followed by nucleophilic
ring opening of the epoxide has been utilized to produce polyols.
These polyols have been used as monomers for the production
of useful polyurethanes (Guo et al., 2000). Our research group
has also developed methodology utilizing ozonolysis of alkenes,
followed by catalytic hydrogenation to produce polyols from veg-
et al., 2007).
Transition metal-catalyzed trimerization of alkyne fatty acid
compounds provides an alternative method for the preparation of
highly functionalized aromatic polyols. Since Reppe and Schweck-
endiek reported the first cyclotrimerization of acetylene in 1948
with nickel as a catalyst to yield benzene derivatives (Reppe
and Schweckendiek, 1948), various transition metal catalysts for
cyclotrimerization have been reported. Among these catalysts,
palladium is the most commonly used. In 1987, Jhingan and
Maier reported a simple way to make substituted benzenes in
the presence of Pd/C (Jhingan and Maier, 1987). This method-
ology has since been applied in the cyclotrimerization of long
chain alkyne fatty acid compounds by a number of research
groups. Augustin performed some unpublished work where aro-
matic polyols were produced by cyclotrimerization of alkyne fatty
acid material (Biermann et al., 2000). In 1990, Renga et al. patented
an approach to producing hexa-substituted benzene derivatives
from alkyne fatty alcohols, acids and esters (Renga et al., 1990).
The trimer products were a mixture of symmetric and asymmet-
ric isomers. Galia and co-workers have synthesized aromatic triols
from the esters of oleic acid, but have reported that the mixture
of symmetric and asymmetric triols were inseparable (Lligadas et
al., 2007). Recently, our group has successfully isolated and char-
acterized these two triol isomers (Yue and Narine, 2008). All these
previous studies on the cyclotrimerization of fatty alkynes utilized
∗
Corresponding author. Tel.: +1 780 492 9081; fax: +1 780 492 7174.
E-mail address: Suresh.narine@ualberta.ca (S.S. Narine).
0009-3084/$ – see front matter © 2008 Elsevier Ireland Ltd. All rights reserved.
doi:10.1016/j.chemphyslip.2008.06.005

44
D. Song, S.S. Narine / Chemistry and Physics of Lipids 155 (2008) 43–47
asymmetric alkynes with one terminal functional group. That
resulted in mixture of symmetric and asymmetric hexa-
30.1, 29.8, 28.1, 26.1; HRMS (ESI) calcd for C18 H31O4Br2 ([M−H]−)
a
469.0584, found: 469.0593.
substituted benzene derivatives with three terminal functionalized
groups and three unfunctionalized alkyl groups. These three
unfunctionalized alkyl groups become dangling chains in any fur-
ther polymerization reactions. Since these unsupported dangling
chains do not support stress, these would significantly affect the
mechanical properties of resulting polymers. We report here an
approach to synthesize a single highly symmetric aromatic hexa-ol
from symmetric fatty acid alkyne derivatives, to produce fully func-
tionalized groups around the aromatic ring omitting any dangling
alkyl chains. This novel polyfunctional hexa-ol is a novel poten-
tial monomer for the production of polyurethanes, polyesters and
polyamides with interesting properties.
2.3. Alkyne-˛,␻-dicarboxylic acid 5/6
Dibromide compound 3 (1.0 g, 2.12 mmol) was dissolved in
DMSO (20 mL). Potassium tert-butoxide (2.37 g, 21.2 mmol) was
then added. The reaction mixture was heated at 100 ◦C for 2 h. Then
the solution was poured into 2N HCl (60 mL) at room temperature.
The precipitate was filtered, washed with water and dried over the
airto givecrude light yellowsolid 5/6 (520 mg, 83%yield). IR (Micro-
scope) 3100–2500 (OH of carboxylic acid), 1688 (C O) cm−1 1H
;
NMR (500 MHz, CD3OD) ı 2.27 (t, 4H, J = 7.4 Hz, CH2–COOH), 2.11 (t,
4H, J = 6.6 Hz, CH2–CC), 1.59 (quintet, 4H, J = 7.4 Hz, CH2–CH2COOH),
1.50–1.28 (m, 16H); 13C NMR (125 MHz, CD3OD) ı 177.7 (C O), 80.9
(CC), 34.9, 30.2 (two carbon overlap), 29.9, 29.7, 26.1, 19.4; HRMS
(ESI) calcd for C18 H29O4 ([M−H]−) 309.2060, found: 309.2058.
2. Experimental
Oleic acid (90%), and all other chemicals and reagents were pur-
chased from Sigma–Aldrich Co., USA. Silica gel (230–400 mesh) was
obtained from Rose Scientific Ltd., AB, Canada. TLC plate (250 ␮m)
was obtained from Silicycle Chemistry Division, QC, Canada. FTIR
spectra were measured with a Mattson Galaxy Series FT-IR 3000
spectrophotometer. 1H NMR and 13C NMR were recorded on Var-
ian 500 MHz spectrometers (Varian, Inc., California, USA) with
CDCl3 or CD3OD as a solvent. Mass spectra were acquired on a
Mariner Biospectrometry ESI system (PerSeptive Biosystems Inc.,
Massachusetts, USA) or Kratos Analytical MS-50 (Kratos Analytical
Ltd., Manchester, UK) EI high-resolution spectrometer.
2.4. Alkyne-˛,␻-dicarboxylic ester 7
To a solution of diacid 5/6 (520 mg, 1.68 mmol) in methanol
(20 mL) was added one drop of concentrated sulphuric acid. The
reaction mixture was refluxed for 1 h. The solvent was evaporated
under the reduced pressure and the residue was purified by column
chromatography to afford alkyne ester 7 (381 mg) and allene ester
8 (142 mg) as colorless oils.
IR (Microscope) 1741 (C O) cm−1 1H NMR (500 MHz, CDCl3)
;
ı 3.66 (s, 6H, CH3–O), 2.30 (t, 4H, J = 7.4 Hz, CH2–COOH), 2.12
(t, 4H, J = 7.0 Hz, CH2–CC), 1.65–1.58 (quintet, 4H, J = 7.4 Hz,
CH2–CH2COOH), 1.46 (quintet, 4H, J = 6.9 Hz, CH2–CC), 1.40–1.22
(m, 14H); 13C NMR (125 MHz, CDCl3) ı 174.2 (C O), 80.1 (CC), 51.4
(CH3–O), 34.1, 29.05, 29.03, 28.8, 28.6, 24.8, 18.7; HRMS (ESI) calcd
for C20H34O4Na ([M+Na]+) 361.2349, found: 361.2342.
2.1. Unsaturated-˛,␻-dicarboxylic acid 2
To oleic acid (100.0 g, 319.0 mmol) was added Grubbs catalyst
(second generation) (27 mg, 3.19 × 10−2 mmol) under the protec-
tion of nitrogen. The solution was stirred by mechanical stirrer and
heated to 45 ◦C. After an hour, the solution became cloudy. The reac-
tion was further stirred for 14 h to obtain a white sticky solution.
Then ethyl vinyl ether (5 mL) was added and the mixture allowed to
stir for half an hour to quench the Grubbs catalyst. The mixture was
recrystallized twice from hexanes (300 mL) and EtOAc (50 mL) to
afford a white power as the product (26.4 g, 53% yield). IR (Micro-
2.5. Allene-˛,␻-dicarboxylic ester 8
IR (Microscope) 1960 (C
C
C), 1741 (C O) cm−1
;
1H NMR
CH), 2.28 (t,
(500 MHz, CDCl3) ı 5.03 (quintet, 2H, J = 4.8 Hz, CH
2H, J = 7.4 Hz, CH2–COOCH3), 2.28 (t, 2H, J = 7.5 Hz, CH2–COOCH3),
C
1.98–1.91 (m, 4H, CH2-CH C), 1.64–1.56 (m, 4H, CH2–CH2COOCH3),
1.42 1.26 (m, 16H); 13C NMR (125 MHz, CDCl3) ı 203.8 (CH
C
CH),
scope) 3200–2500 (OH of carboxylic acid), 1697 (C O) cm−1 1H
;
174.2 (C O), 174.1 (C O), 90.9 (CH
C CH), 90.7 (CH C CH), 51.4
NMR (500 MHz, CD3OD) ı 5.39–5.36 (m, 2H, CH CH), 2.27 (t, 4H,
J = 7.4 Hz, CH2–COOH), 1.99–1.94 (m, 4H, CH2–CH CH), 1.59 (quin-
tet, 4H, J = 7.4 Hz, CH2–CH2COOH), 1.38–1.26 (m, 18H); 13C NMR
(125 MHz, CD3OD) ı 177.7 (C O), 131.5 (CH CH), 34.9, 33.6, 30.7,
30.24, 30.22, 30.0, 26.1; HRMS (ESI) calcd for C18 H31O4 ([M−H]−)
311.2217, found: 311.2214.
(CH3–O, two carbon overlap), 34.1, 34.0, 29.1, 29.09, 29.04, 28.95
(two carbon overlap), 28.92, 28.867, 28.861, 28.7, 24.91, 24.90;
HRMS (ESI) calcd for C20H34O4Na ([M+Na]+) 361.2349, found:
361.2356.
2.6. Aromatic hexa-ester 9
2.2. Dibromide-˛,␻-dicarboxylic acid 3
To a solution of alkyne ester 7 (4.0 g, 11.8 mmol) in THF (50 mL)
was added chlorotrimethylsilane (3.7 mL, 29.6 mmol) and Pd/C
(500 mg). The reaction mixture was refluxed for 4 h and cooled to
room temperature. The mixture was then filtered to remove Pd/C
which was washed with ethyl acetate (50 mL). The resulting solu-
tion was further washed water (50 mL), brine (50 mL) and dried
over MgSO4. The solvent was evaporated under the reduced pres-
sure and the residue was purified by column chromatography to
afford product 9 (3.5 g, 87% yield) as a colorless oil.
To the solution of unsaturated diacid 2 (19.0 g, 60.8 mmol) in
diethyl ether (300 mL) was added bromine (3.8 mL, 73.0 mmol)
dropwise via addition funnel over 30 min. The solid dissolved and
the solution became light red. The solution was stirred for another
30 min. Then saturated sodium thiosulfate (20 mL) was added to
reduce any excess bromine. The resulting organic phase was sep-
arated and washed with brine (20 mL) and dried over MgSO4. The
ether solvent was evaporated under reduced pressure. The resulting
solid was crystallized with hexanes (200 mL) and EtOAc (200 mL)
to give a white powder as the product (24 g, 83% yield). IR (Micro-
IR (Microscope) 1741 (C O) cm−1
;
1H NMR (500 MHz, CDCl3)
ı
3.67 (s, 18H, CH3–O), 2.50–2.43 (m, 12H, CH2Ph), 2.33
scope) 3200–2500 (OH of carboxylic acid), 1693 (C O) cm−1
;
1H
(t, 12H, J = 7.4 Hz, CH2–COOCH3), 1.65 (quintet, 12H, J = 7.3 Hz,
CH2–CH2COOCH3), 1.52–1.28 (m, 48H); 13C NMR (125 MHz, CDCl3)
( 174.2 (C O), 136.5 (C C), 51.4 (CH3–O), 34.1, 31.6, 30.5, 29.8, 29.2,
29.1, 24.9; HRMS (ESI) calcd for C60H102O12Na ([M+Na]+) 1037.7263,
found: 1037.7250.
NMR (500 MHz, CD3OD) ı 4.29–4.23 (m, 2H, CH–Br), 2.30 (t, 4H,
J = 7.4 Hz, CH2–COOH), 2.15–2.07 (m, 2H, CH–CHBr), 1.98–1.90 (m,
2H, CH–CHBr), 1.68–1.56 (m, 6H), 1.50–1.28 (m, 14H); 13C NMR
(125 MHz, CD3OD) ı 177.6 (C O), 61.3 (CH–Br), 37.8, 34.9, 30.2,

D. Song, S.S. Narine / Chemistry and Physics of Lipids 155 (2008) 43–47
45
Scheme 1. Preparation of alkyne ␣,␻-dicarboxylic acid 5.
2.7. Aromatic hexa-ol 10
poor solubility in diethyl ether, THF was first chosen as the solvent.
However, the bromination reaction in THF does not proceed satis-
factorily. It would appear, from analysis of NMR spectra that THF
participates in the reaction. Interestingly, when diethyl ether was
used as the solvent, solid dicarboxylic acid 2 was slowly consumed
with the addition of bromine to afford dibromide compound 3 in
good yield. By subjecting dibromide 3 to basic conditions (Silbert,
1984; Augustin and Schafer, 1991) the only product isolated was
vinyl bromide 4. A tiny amount of desired alkyne 5 derived from the
cis-isomer of compound 2 was observed from the NMR spectrum
of the crude products. This amount remained unchanged when the
reaction was left to stir overnight. Based on these observations;
potassium hydroxide is not a strong enough base to effect the sec-
ond HBr elimination. Therefore, potassium tert-butoxide in DMSO,
a stronger base than KOH, was then tried. When dibromide com-
pound 3 was heated with potassium tert-butoxide in DMSO, two
inseparable isomers alkyne 5 and allene 6 were formed at a ratio of
2.7:1.
To a solution of hexa-ester 9 (270.0 mg, 0.3 mmol) in THF (10 mL)
was added lithium aluminum hydride (88.2 mg, 2.3 mmol). The
reaction mixture was stirred for 2 h. Then ethyl acetate (5 mL)
and water (5 mL) was added to quench excess lithium aluminum
hydride. The solution was diluted with ethyl acetate (30 mL) and 2N
HCl was added until the solution became clear. The organic phase
was separated and washed with water (20 mL), brine (20 mL) and
dried over MgSO4. The solvent was then evaporated under reduced
pressure and the residue was purified by column chromatography
to afford aromatic polyol (230 mg, 94% yield) as a colorless sticky
oil. IR (Microscope) 3318 (OH) cm−1 1H NMR (500 MHz, CDCl3) ı
;
3.65 (t, 12H, J = 7.6 Hz, CH2–OH), 2.52–2.45 (m, 12H, CH2Ph), 1.78
(brs, 6H, OH), 1.62–1.25 (m, 72H); 13C NMR (125 MHz, CDCl3) ı
136.7 (C C), 62.9 (CH2–OH), 32.8, 31.4, 30.5, 29.7, 29.4, 29.3, 25.8;
HRMS (ESI) calcd for C54H102O6Na ([M+Na]+) 869.7568, found:
869.7574.
Comparing the mechanisms of bromination and dehydro-
bromination of cis-oleic acid and trans-unsaturated diacid 2, an
explanation for the formation of allene 6 can be given. When
oleic acid was brominated, enantiomers a and b were produced
(Scheme 2). Since brominated oleic acid is a non-symmetrical
molecule, there will be two possible pathways for the first HBr elim-
ination. Based on the rule of antiperiplanar elimination, the first
HBr elimination of isomers a and b would result in olefin c and d.
Both c and d are trans-olefins that make the second HBr elimination
much easier based on the antiperiplanar elimination rule.
3. Results and discussion
Oleic acid, as an economic mono-unsaturated fatty acid, was
used to synthesize unsaturated-␣,␻-dicarboxylic acids. By solvent
free self-metathesis, oleic acid was converted into unsaturated-
␣,␻-dicarboxylic acid 2 in the presence of second-generation
Grubbs catalyst in 53% yield. The metathesis products consisted
of the major trans-alkene and minor cis-alkene at a ratio of 91:9
by NMR spectrum (Scheme 1) (Ngo et al., 2006). Since 2 has very
Scheme 2. Mechanism of dehyrobromination of oleic acid.

46
D. Song, S.S. Narine / Chemistry and Physics of Lipids 155 (2008) 43–47
Scheme 3. Mechanism of dehydrobromination of trans-unsaturated diacid 2.
Scheme 4. Preparation of aromatic hexa-ol 10.
However, in the case of symmetric diacid 2, bromination only
reduced by the treatment of LAH to obtain hexa-ol 10 in excellent
yield (94%).
In conclusion, we have reported a simple route for the synthesis
of highly functional aromatic hexa-ol 10. This general method can
be applied to the synthesis of aromatic hexa-ols or hexa-cids from
other simple unsaturated fatty acid.
gave one single isomer e (Scheme 3). After the first HBr elimina-
tion of isomer e, the cis-olefin f was obtained. Having obtained the
cis-olefin, it is now quite difficult for the second HBr elimination
to occur due to the weak basicity of KOH. When a stronger base,
potassium tert-butoxide, is used, there are two possible acidic pro-
tons in isomer f that can be deprotonated. Deprotonation at these
two sites can afford the corresponding carbanion intermediates g
and h, which can then eliminate bromide to give desired alkyne 5
and undesired allene 6.
The inseparable mixture of compounds 5 and 6 was first
cyclotrimerized in the presence of palladium and TMSCl, however
only 30% of the desired hexa-ol was obtained. Some side products
were slowly generated as the reaction proceeded. This may be due
to the presence of the allene impurity in the reaction since the
allene may also form a complex with the palladium catalyst in a
competing side reaction. In the crude NMR spectrum of the reac-
tion mixture, two aromatic proton signals which may derive from
allene moiety are observed above 7 ppm. Based on this observa-
tion, carboxylic groups of 5 and 6 were methylated with catalytic
amount of concentrated sulfuric acid in methanol (Scheme 4).
The resulting diester compounds 7 and 8 were separated by flash
chromatography. The alkyne fatty ester was then trimerized to
afford hexa-ester 9 in good yield (87%). Hexa-ester 9 was then
Acknowledgements
The financial support of Bunge Oils, NSERC, Alberta Canola Pro-
ducers Commission, Alberta Agricultural Research Institute and
Alberta Crop Industry Development Fund are gratefully acknowl-
edged.
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