Highly fluorinated C18 fatty acids: Synthesis and interfacial properties

Article abstract of DOI:10.1016/j.jfluchem.2004.09.017

A fluorinated oleic acid 1-Z containing a perfluorooctyl group and its analogues (E-isomer 1-E, alkyne type 2 and saturated type 3) were synthesized in good yields. In these syntheses, it was found that a key compound 5 could be converted to each of 1-Z, 1-E and 2. Furthermore, equilibrium spreading pressures of their monolayers at the air-water interface were measured in order to demonstrate how the degree of unsaturation in the hydrophobic chain, the geometric isomerization, and the presence of F-atoms influence the monolayer stability. Irrespective of the structural alteration in the hydrophobic chains, the fluorinated fatty acids formed more stable monolayers with high spreading pressures as compared to their hydrocarbon counterparts.

Full text of DOI:10.1016/j.jfluchem.2004.09.017

Journal of Fluorine Chemistry 125 (2004) 1959–1964
www.elsevier.com/locate/fluor
Highly fluorinated C18 fatty acids: synthesis
and interfacial properties
*
Katsuki Takai, Toshiyuki Takagi , Teruhiko Baba, Toshiyuki Kanamori
Research Center of Advanced Bionics (RCAB), National Institute of Advanced Industrial Science and
Technology (AIST), AIST Tsukuba Central 5, 1-1-1 Higashi, Tsukuba, Ibaraki 305-8565, Japan
Received 30 June 2004; received in revised form 24 August 2004; accepted 3 September 2004
Available online 28 October 2004
Abstract
A fluorinated oleic acid 1-Z containing a perfluorooctyl group and its analogues (E-isomer 1-E, alkyne type 2 and saturated type 3) were
synthesized in good yields. In these syntheses, it was found that a key compound 5 could be converted to each of 1-Z, 1-E and 2. Furthermore,
equilibrium spreading pressures of their monolayers at the air–water interface were measured in order to demonstrate how the degree of
unsaturation in the hydrophobic chain, the geometric isomerization, and the presence of F-atoms influence the monolayer stability.
Irrespective of the structural alteration in the hydrophobic chains, the fluorinated fatty acids formed more stable monolayers with high
spreading pressures as compared to their hydrocarbon counterparts.
# 2004 Elsevier B.V. All rights reserved.
Keywords: Fluorocarbon; Fluorinated fatty acid; Oleic acid; Elaidic acid; Stearic acid; Equilibrium spreading pressure; Monolayer
1. Introduction
monolayers at the air–water interface, in order to
demonstrate how the degree of unsaturation in the
hydrophobic chain, the geometric isomerization, and the
presence of F-atoms influence the monolayer stability.
Fluorinated compounds have attracted much attention
from the viewpoint of their unique characteristics such as
thermal and chemical stability, surface tension lowering
ability, hydrophobicityandlipophobicity[1–3]. Thesynthesis
andcharacterizationofavariety offluorinatedfattyacidshave
been described by many authors [4–9]. So far, only Buchanan
et al. have studied the synthesis of oleic acid containing
perfluorohexyl group [7,9]. They reported synthesis and
assignment by 19F NMR spectrum of the compound [9].
In this paper, we report the synthesis of a highly
fluorinated oleic acid 1-Z in which a fluorocarbon moiety is
bonded directly to a C–C double bond. We have also
achieved synthesis of the analogues of 1-Z (E-isomer 1-E,
alkyne type 2 and saturated type 3) in good yields (Fig. 1). In
these reactions, we obtained the key compound 5 that could
be converted to each of 1-Z, 1-E and 2. Furthermore, we
measured equilibrium spreading pressures (pes) of their
2. Results and discussion
We planned to develop new kinds of lipids containing a
fluorocarbon group. As the first step, we have synthesized
highly fluorinated C18 fatty acids.
(Z)-11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,18,18-
heptadecafluoro-9-octadecenoic acid 1-Z as a derivative of
oleic acid, and E-isomer 1-E as a derivative of elaidic acid
were synthesized by the following procedures.
9-Decyn-1-ol 4 was prepared using the Zipper reaction [10]
from 3-decyn-1-ol in 91% yield. Perfluorooctyl iodide reacted
with 4 in the presence of Na2S2O4 as a free radical initiator
[5,11] to give alkenyl iodide 5 in 70% yield as E/Z mixture
(E:Z = 77:23). 5 was easily separated into E-isomer 5-E and Z-
isomer 5-Z using a column chromatography. Each configura-
tion was determinedfrom1Hand19FNMR spectra (Scheme1).
* Corresponding author. Tel.: +81 29 861 4698; fax: +81 29 861 4651.
E-mail address: t.takagi@aist.go.jp (T. Takagi).
0022-1139/$ – see front matter # 2004 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2004.09.017

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K. Takai et al. / Journal of Fluorine Chemistry 125 (2004) 1959–1964
Table 1
Equilibrium spreading pressures (pes) of fluorinated fatty acids and their
hydrocarbon counterpartsa
Fluorinated fatty acid pe (mN/m) Fatty acid
pe (mN/m)
1-Z
1-E
2
45.4
33.2
43.7
29.8
Oleic acid
31.4
13.6
9.7
Elaidic acid
9-Octadecynoic acidb
Stearic acidb
Fig. 1. Synthesized fluorinated C18 fatty acids.
3
<0.1
a
On pure water (pH ꢀ6); 25 8C.
b
Ref. [13].
75% overall yield (Scheme 3, routes a–c). 7 was oxidized by
the Jones reagent, and successively purified with a column
chromatography to give 2 in 83% yield (Scheme 3).
Thus, we found that 5 was a key compound that could be
converted to each of 1-Z, 1-E and 2.
Finally, 11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,
18,18-heptadecafluorooctadecanoic acid 3 as a derivative
of stearic acid was synthesized by following procedure.
Perfluorooctyl iodide reacted with 9-decen-1-ol in the
presence of Na2S2O4 to give alkyl iodide 10. 10 was
deiodinated with Zn to give 11 in the presence of catalytic
amount of NiCl2Á6H2O. 11 was oxidized by the Jones
reagent, and successively purified to give 3 (Scheme 4).
The equilibrium spreading pressures (pes) of each fatty
acid are listed in Table 1. At the experimental temperature
(25 8C), 1-Z rapidly spread on the water surface and
exhibited the highest pe value among the fatty acids
examined. On the other hand, 3 gradually (over 30 min)
spread to the pe of 30 mN/m. The obtained pes for
hydrocarbon counterparts, oleic acid (31.4 mN/m) and
elaidic acid (13.6 mN/m) were in agreement with the
literature data [13]. The pes for the hydrocarbon counter-
parts, 9-octadecynoic acid and stearic acid have been
reported as 9.7 and <0.1 mN/m at 25 8C, respectively [13].
As the pe is suggested as a criterion for monolayer stability
[14,15], it is obvious that fluorinated fatty acids form more
stable monolayers with higher spreading pressures at the
air–water interface as compared to their hydrocarbon
counterparts. The interfacial properties of fatty acids vary
considerably depending on the position and degree of
unsaturation in the hydrophobic chain, geometric isomer-
ization, and the presence of heteroatoms [13,16]. In
Scheme 1. Synthesis and separation of 5-E and 5-Z. (a) Na2S2O4, NaHCO3/
CH3CN, H2O, rt, 4 h; (b) silica gel column (EtOAc:hexane = 1:3, 5-E:5-
Z = 77:23).
Scheme 2. Synthesis of a fluorinated oleic acid 1-Z. (a) n-BuLi/ether,
À78 8C, 4 h; (b) Jones reagent/acetone.
5-E was treated with n-BuLi for 4 h at À78 8C to give Z-
isomeric olefin 6-Z in 71% yield [12]. 6-Z was oxidized by
the Jones reagent, and successively purified with a column
chromatography and a recrystallization to give 1-Z in 79%
yield (Scheme 2). E-isomer 1-E was prepared similarly in
54% yield for two steps from 5-Z.
11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,18,18-Hep-
tadecafluoro-9-octadecynoic acid 2 was synthesized from
E/Z mixture iodide 5 by the following procedures. We tried
the synthesis in two routes for the alkynyl alcohol 7 (as the
precursor of 2). In one route, when 5 was treated with t-
BuOK [4,11] directly, 7 was obtained in 51% yield (Scheme
3, route A). In another route, 5 was protected by a
tetrahydropyranyl group at first, and was continuously
treated with t-BuOK, and was finally deprotected to give 7 in
Scheme 3. Synthesis of a fluorinated alkynoic acid 2. (a) DHP, PPTS/CH2Cl2, rt, overnight; (b) t-BuOK/ether, À20 8C, 1 h, then 0 8C, 2 h; (c) PPTS/EtOH,
55 8C, 1 h; (d) Jones reagent/acetone; (A) t-BuOK/ether, À20 8C, 1 h, then 0 8C, 2 h.

K. Takai et al. / Journal of Fluorine Chemistry 125 (2004) 1959–1964
1961
and these impurities might contribute to a certain extent to
the spreading pressure of 3. Even if there might be some
influences of the impurities on the interfacial behavior of 3,
it is reasonable to assume that the spreading pressure of 3
itself is higher than that of stearic acid.
In summary, we successfully synthesized highly fluori-
nated fatty acids 1-Z, 1-E, 2 and 3 in good yields. Their
equilibrium spreading pressures (pes) 3 were much higher
than those of their hydrocarbon counterparts, indicating that
the highly fluorinated fatty acids formed more stable
monolayers with high spreading pressures.
Scheme 4. Synthesis of a fluorinated stearic acid 3. (a) Na2S2O4, NaHCO3/
CH3CN, H2O, rt, 4 h; (b) Zn, NiCl2/THF, H2O, rt, overnight; (c) Jones
reagent/acetone.
particular, partially fluorinated fatty acids are known to be
extremely surface-active and extremely hydrophobic [17],
therefore, they are expected to form stable insoluble
monolayers at the air–water interface.
3. Experimental
The pe strongly depends on several conditions, e.g., the
temperature of the subphase and the state of the bulk lipid
phase. In cases of simple fatty acids, the maximal spreading
pressures are observed at their bulk melting points, and the
temperature coefficient of the spreading pressure can be well
correlated with the heat of fusion of fatty acid crystals [16].
Among the fluorinated fatty acids used in this study and their
hydrocarbon counterparts, 1-Z, 2, and oleic acid (mp
13.3 8C, [18]) are in a liquid form at 25 8C and the others,
1-E(mp57–58 8C),3(mp72–79 8C),elaidicacid(mp44.5 8C
[18]), 9-octadecynoic acid (mp 47–48 8C [19]), stearic acid
(mp 69.7 8C [18]) are in a solid form. Therefore, it is
reasonable that the high spreading pressures could be
observed for a liquid 1-Z and a liquid 2. As a rule, melting
point is a measure of the cohesive force in the fatty acid
crystals. Judging from the melting points of E-monoene
acids (elaidic acid and 1-E) and saturated acids (stearic acid
and 3) except monoyne acids (9-octadecynoic acid and 2),
the replacement of the C8H17 tail in the C18 fatty acids by the
C8F17 one appears to enhance the crystallinity of the fatty
acids in solid form. The spreading pressures of the fatty
acids below their melting points are strongly temperature-
dependent and considerably low as compared to liquid fatty
acids [16]. However, the pes of the solid fluorinated fatty
acids are much higher than those of their hydrocarbon
counterparts as described above. This suggests the inter-
molecular interactions of the fluorinated fatty acids in the
crystals might be weaker and/or the fatty acid–water
interactions might be stronger than those of the hydrocarbon
counterparts. Based on the observations that the low
polarizability of the F-atom results in the low intermolecular
van der Waals forces and the low cohesive energy densities
in liquid fluorocarbons [17], it is likely that the interactions
between hydrophobic chains of fluorinated fatty acids in
crystals are much weaker than hydrocarbon counterparts
leading to higher spreading pressures, although a definite
conclusion awaits further studies on the temperature-
dependent spreading pressure measurements of fluorinated
fatty acid monolayers. It should be noted here that 3 used in
this study exhibited a broad melting point (72–79 8C),
suggesting the existence of impurities in the main product,
3.1. Instruments
1H NMR spectra were measured with a JEOL JNM-LA
500 FT NMR system (500 MHz) using TMS as an internal
standard. 19F NMR spectra were measured with a JEOL
JNM-LA 500 FT NMR system (500 MHz) or a JEOL JNM-
LA 300 (300 MHz) using benzotrifluoride (BTF) as an
internal standard. FT-IR spectra were measured with a
JASCO FT/IR-680 plus. Mass spectra (ESI-MS) were
measured with a JEOL JMS-700T Tandem MStation.
Column chromatography purifications were carried out
using silica gel 60 (Merck 7734).
3.2. Materials
Fluorinated fatty acids 1-E, 1-Z, 2 and 3 were synthesized
by the following procedures. Perfluorooctyl iodide was
purchased from DAIKIN Finechemical Laboratory and its
purity was over 95% (GC). 3-Decyn-1-ol and 9-decen-1-ol
were purchased from Tokyo Kasei Kogyo Co. and their
purities were over 96% (GC) and 95% (GC), respectively.
Oleic acid and elaidic acid were purchased from Sigma Co.
and their purities were approximately 99%. The water used
was prepurified with a homemade purification system (RO
membrane, ion-exchange column, and 0.22 mm filter) and
was further purified with a Milli-Q Labo system (Millipore
Corp., Bedford, MA) and distillation in an all-glass still. Its
resistivity was higher than 18 MV cm.
3.2.1. 9-Decyn-1-ol (4)
To sodium hydride (60% in oil) (19.90 g, 0.50 mol) at an
ice bath was added 1,3-diaminopropane (175 mL). The
suspension was heated gradually to 80 8C over a period of
2 h with stirring, was cooled to 10 8C, and 3-decyn-1-ol
(25.0 mL, 0.14 mol) was added gradually over a period of
5 min, successively. The mixture was heated gradually to
100 8C over 40 min, and stirred for 80 min at 100 8C. The
mixture was cooled in an ice bath, and cautiously poured
into crushed ice, and then extracted with n-hexane. The
organic layers were washed with H2O, satd NaHCO3 aq, and
satd NaCl aq, successively, and then dried over MgSO4.

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K. Takai et al. / Journal of Fluorine Chemistry 125 (2004) 1959–1964
After filtration and evaporation of the solvent, the residue
was distilled to give 9-decyn-1-ol (4) (20.02 g, 91.4%)
[91.5–92.0 8C/4 mmHg].
12.78 Hz, H10), 6.11 (1H, dtt, J = 11.88, 7.77, 2.21 Hz, H9).
19F NMR (CDCl3) ppm: À18.00 (3F, t, J = 10.04 Hz, F18),
À43.85 (2F, q, J = 13.17 Hz, F11), À58.72 (2F, bs, F12),
À58.94 to À59.54, À59.98, À60.56 to À61.14 (2F, 4F, 2F,
m, bs, m, F13–F16), À63.14 to À63.62 (2F, m, F17).
1H NMR (CDCl3) d: 1.20–1.43 (8H, m, H3–H6), 1.43–
1.63 (4H, m, H2, H7), 1.94 (2H, t, J = 2.75 Hz, H10), 2.18
(2H, dt, J = 7.16, 2.81 Hz, H8), 3.64 (2H, t, J = 6.70 Hz,
H1).
3.2.4. (E)-11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,
18,18-Heptadecafluorooctadec-9-en-1-ol (6-E)
3.2.2. (E)- and (Z)-11,11,12,12,13,13,14,14,15,15,16,16,
17,17,18,18,18-heptadecafluoro-9-iodo-octadec-
9-en-1-ol (5-E, 5-Z)
6-E was prepared from 5-Z, similarly (68.9%).
1H NMR (CDCl3) d: 1.28–1.44 (8H, m, H3–H6), 1.44–
1.52 (2H, m, H2), 1.57 (2H, dq, J = 7.12 Hz, H7), 2.15–2.25
(2H, m, H8), 3.64 (2H, t, J = 5.84 Hz, H1), 5.59 (1H, dd,
J = 15.22, 12.78 Hz, H10), 6.38 (1H, dtt, J = 15.73, 6.81,
2.15 Hz, H9). 19F NMR (CDCl3) ppm: À18.02 (3F, t,
J = 9.07 Hz, F18), À48.48 (2F, q, J = 12.08 Hz, F11),
À58.74 (2F, bs, F12), À59.23, À59.99, À60.81 (2F, 4F,
2F, bs, bs, bs, F13–F16), À63.39 (2F, bs, F17).
To a solution of 4 (2.00 g, 0.13 mol) in CH3CN (18 mL)
and deionized H2O (9 mL) was added perfluorooctyl iodide
(8.50 g, 0.16 mol), NaHCO3 (545 mg, 6.48 mmol) and 80%
Na2S2O4 (1.41 g, 6.48 mmol) at 0 8C, and then the mixture
was stirred for 4 h at room temperature. The mixture was
diluted with deionized H2O, and then extracted with Et2O.
The organic layers were washed with satd NaCl aq, and then
dried over MgSO4. After filtration and evaporation of the
solvent, the residue was purified by a column chromato-
graphy (EtOAc/n-hexane, 25%) to give (E)-11,11,12,12,
13,13,14,14,15,15,16,16,17,17,18,18,18-heptadecafluoro-9-
iodooctadec-9-en-1-ol (5-E) (4.88 g, 53.6%) and Z-isomer
5-Z (1.47 g, 16.1%). E:Z = 77:23.
3.2.5. (Z)-11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,
18,18-Heptadecafluorooctadec-9-enoic acid (1-Z)
To 6-Z (129 mg, 0.23 mmol) in acetone (2.5 mL) was
added the Jones reagent at room temperature till the color of
the chromium ion remained visible for 10 min. The mixture
was quenched with 2-propanol. After filtration and
evaporation of solvents, the residue was extracted with
EtOAc. The organic layers were washed with satd NaCl aq,
and then dried over MgSO4. After filtration and evaporation
of the solvent, the residue was recrystallized in n-hexane at
À20 8C to give (Z)-11,11,12,12,13,13,14,14,15,15,16,16,
17,17,18,18,18-heptadecafluorooctadec-9-enoic acid (1-Z)
(105.0 mg, 79.3%).
1H NMR (CDCl3) d: 1.25–1.38 (6H, m, H4–H6), 1.38–
1.48 (2H, m, H3), 1.57–1.70 (2H, m, H7), 2.27–2.40 (2H, m,
H8), 2.35 (2H, t, J = 7.46 Hz, H2), 5.48 (1H, dd, J = 12.48,
15.53 Hz, H10), 6.11 (1H, dtt, J = 11.95, 7.65, 2.23 Hz, H9).
19F NMR (CDCl3) ppm: À18.02 (3F, t, J = 10.33 Hz, F18),
À43.88 (2F, q, J = 13.17 Hz, F11), À58.70 (2F, bs, F12),
À59.19, À60.00, À60.98 (2F, 4F, 2F, bs, bs, bs, F13–F16),
À63.38 (2F, bs, F17). IR (cmÀ1): 1712.48 (C=C). ESI-MS
(m/z): calcd. for C18H17F17O2 [M]+ 588.0957, found
588.0965.
1
5-E: H NMR (CDCl3) d: 1.27–1.45 (8H, m, H3–H6),
1.50–1.65 (4H, m, H2, H7), 2.63 (2H, dd, J = 7.46 Hz, H8),
3.65 (2H, t, J = 6.71 Hz, H1), 6.32 (1H, t, J = 14.47 Hz,
H10). 19F NMR (CDCl3) ppm: À18.02 (3F, t, J = 10.80 Hz,
F18), À42.62 (1F, q, J = 15.18 Hz, F11), À58.70 (2F, bs,
F12), À59.16, À59.97, À60.50 (2F, 4F, 2F, bs, bs, bs, F13–
F16), À63.37 (2F, bs, F17).
1
5-Z: H NMR (CDCl3) d: 1.15–1.29 (8H, m, H3–H6),
1.52–1.65 (4H, m, H2, H7), 2.66 (2H, dd, J = 7.46 Hz, H8),
3.65 (2H, t, J = 6.69 Hz, H1), 6.24 (1H, t, J = 13.10 Hz,
H10). 19F NMR (CDCl3) ppm: À18.05 (3F, t, J = 10.80 Hz,
F18), À45.70 (1F, q, J = 10.80 Hz, F11), À58.67 (2F, bs,
F12), À58.58 to À59.53, À59.60 to À60.01, À60.20 (2F, 4F,
2F, m, m, bs, F13–F16), À63.40 (2F, bs, F17).
3.2.3. (Z)-11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,
18,18-Heptadecafluorooctadec-9-en-1-ol (6-Z)
1.6 M n-BuLi/hexane (0.88 mL, 1.37 mmol) was
dropped to a solution of 5-E (200 mg, 0.29 mmol) in dry
THF (3 mL) at À78 8C. The mixture was stirred for 4 h, and
then quenched with pre-cooled (À78 8C) methanol
(0.88 mL). After being warmed to 0 8C, the mixture was
poured into satd NH4Cl aq (6 mL), and was extracted with
EtOAc. The organic layers were washed with satd NaCl aq,
and then dried over MgSO4. After filtration and evaporation
of solvent, the residue was purified by a column
chromatography (EtOAc/n-hexane, 15%) to give (Z)-
11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,18,18-hepta-
decafluorooctadec-9-en-1-ol (6-Z) (116.6 mg, 71.0%).
1H NMR (CDCl3) d: 1.20–1.39 (8H, m, H3–H6), 1.39–
1.50 (2H, m, H2), 1.52–1.63 (2H, m, H7), 2.25–2.37 (2H, m,
H8), 3.64 (2H, t, J = 6.54 Hz, H1), 5.48 (1H, dd, J = 15.37,
3.2.6. (E)-11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,
18,18-Heptadecafluorooctadec-9-enoic acid (1-E)
1-E was prepared from 6-E, similarly (80.0%).
mp 57.0–57.9 8C. 1H NMR (CDCl3) d: 1.25–1.39 (6H, m,
H4–H6), 1.40–1.51 (2H, m, H3), 1.57–1.74 (2H, m, H7),
2.14–2.25 (2H, m, H8), 2.35 (2H, t, J = 7.46 Hz, H2), 5.59
(1H, dd, J = 15.57, 11.93 Hz, H10), 6.40 (1H, dtt, J = 16.05,
7.03, 2.29 Hz, H9). 19F NMR (CDCl3) ppm: À17.95 (3F, t,
J = 10.80 Hz, F18), À48.40 (2F, q, J = 10.80 Hz, F11),
À58.63 (2F, bs, F12), À59.15, À59.94, À60.73 (2F, 4F, 2F,
bs, bs, bs, F13–F16), À62.99 to À63.97 (2F, m, F17). IR
(cmÀ1): 1699.94 (C=C). ESI-MS (m/z): calcd. for
C18H17F17O2 [M]+ 588.0957, found 588.0959.

K. Takai et al. / Journal of Fluorine Chemistry 125 (2004) 1959–1964
1963
3.2.7. 11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,
18,18-Heptadecafluorooctadec-9-yn-1-ol
(7) [Scheme 3, route A]
mixture was stirred for 1 h at À20 8C, and then was
stirred for 2 h at 0 8C, continuously. The mixture was
quenched with 2 M HCl (16 mL), and then was extracted
with Et2O. The organic layers were washed with satd NaCl
aq, and dried over MgSO4. After filtration and evaporation of
the solvent, the residue was purified by a column
chromatography (EtOAc/n-hexane, 2%) to give 11,11,
12,12,-13,13,14,14,15,15,16,16,17,17,18,18,18-heptadeca-
fluoro-1-tetrahydropyranyloxyoctadec-9-yne (9) (891 mg,
76.7%).
1H NMR (CDCl3) d: 1.22–1.65 (16H, m, H2–H7, THP),
1.66–1.77 (1H, m, THP), 1.78–1.90 (1H, m, THP), 2.35 (2H,
q, J = 6.40 Hz, H8), 3.38 (1H, dt, J = 6.50, 9.72 Hz, H1),
3.43–3.56 (1H, m, THP), 3.73 (1H, dt, J = 6.86, 9.57 Hz,
H1), 3.82–3.92 (1H, m, THP), 4.57 (1H, dd, J = 4.45,
2.60 Hz, THP). 19F NMR (CDCl3) ppm: À18.00 (3F, t,
J = 9.71 Hz, F18), À33.22 to À33.62 (2F, m, F11), À58.10
to À58.51 (2F, m, F12), À58.87 to À59.47, À59.62 to
À60.22 (4F, 4F, m, m, F13–F16), À63.15 to À63.56 (2F, m,
F17).
A solution of 5 (2.00 g, 2.86 mmol) in anhydrous Et2O
(30 mL) was added to a solution of t-BuOK (801 mg,
7.14 mmol) in anhydrous Et2O (20 mL), and this mixture
was stirred for 1 h at À20 8C, and then was stirred at 0 8C,
continuously. The mixture was quenched with 2 M HCl
(30 mL), and then was extracted with Et2O. The organic
layers were washed with satd NaCl aq, and dried over
MgSO4. After filtration and evaporation of the solvent, the
residue was purified by a column chromatography (EtOAc/
n-hexane, 20%) to give 11,11,12,12,13,13,14,14,15,15,
16,16,17,17,18,18,18-heptadecafluorooctadec-9-yn-1-ol (7)
(794 mg, 51.3%).
1H NMR (CDCl3) d: 1.28–1.47 (8H, m, H3–H6), 1.50–
1.64 (4H, m, H2, H7), 2.35 (2H, dd, J = 6.10, 12.50 Hz, H8),
3.65 (2H, t, J = 6.10 Hz, H1). 19F NMR (CDCl3) ppm:
À18.00 (3F, t, J = 9.71 Hz, F18), À33.21 to À33.72 (2F, m,
F11), À58.15 to À58.49 (2F, m, F12), À58.85 to À59.48,
À59.68 to À60.24 (4F, 4F, m, F13–F16), À63.15 to À63.55
(2F, m, F17).
3.2.10. 11,11,12,12,13,13,14,14,15,15,16,16,17,
17,18,18,18-Heptadecafluorooctadec-9-yn-1-ol (7)
[Scheme 3, route c]
3.2.8. 11,11,12,12,13,13,14,14,15,15,16,16,17,17,
18,18,18-Heptadecafluoro-9-iodo-1-tetrahydro-
To a solution of 9 (500 mg, 0.76 mmol) in ethanol (5 mL)
was added pyridinium p-toluenesulfonate (95.7 mg,
0.38 mmol), and this mixture was stirred for 1 h at 55 8C.
The mixture was diluted with EtOAc. The organic layers
were washed with satd NaCl aq, and then dried over MgSO4.
After filtration and evaporation of the solvent, the residue
was purified by a column chromatography (EtOAc/n-
hexane, 15–20%) to give 7 (428 mg, 98.1%).
pyranyloxyoctadec-9-ene (8) [Scheme 3, route a]
To a solution of 5 (E/Z mixture: 2.20 g, 3.14 mmol) in
CH2Cl2 (16 mL) was added 3,4-dihydro-2H-pyrane
(0.43 mL, 4.71 mmol) and pyridinium p-toluenesulfonate
(16 mg), and this mixture was stirred overnight at room
temperature. The mixture was diluted with CH2Cl2. The
organic layers were washed with satd NaCl aq, and then
dried over MgSO4. After filtration and evaporation of the
solvent, the residue was purified by a column chromato-
graphy (EtOAc/n-hexane, 5%) to give 11,11,12,12,
13,13,14,14,15,15,16,16,17,17,18,18,18-heptadecafluoro-9-
iodo-1-tetrahydropyranyloxyoctadec-9-ene (8) (2.44 g,
99.1%).
1H NMR (CDCl3) d: 1.20–1.67 (16H, m, H2–H7, THP),
1.67–1.77 (1H, m, THP), 1.77–1.90 (1H, m, THP), 2.62 (2H,
t, J = 7.33 Hz, H8), 3.39 (1H, dt, J = 6.70, 9.45 Hz, H1),
3.44–3.58 (1H, m, THP), 3.74 (1H, dt, J = 7.03, 9.32 Hz,
H1), 3.87 (1H, dt, J = 3.35, 7.95 Hz, THP), 4.58 (1H, dd,
J = 4.26, 2.74 Hz, THP), 6.32 (1H, t, J = 14.48 Hz, H10).
19F NMR (CDCl3) ppm: À18.00 (3F, t, J = 9.71 Hz, F18),
À42.57 (2F, q, J = 13.60 Hz, F11), À58.29 to À58.89 (2F,
m, F12), À58.89 to À59.44, À59.59 to À60.24, À60.24 to
À60.64 (4F, 2F, 2F, m, m, m, F13–F16), À63.09 to À63.59
(2F, m, F17).
3.2.11. 11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,
18,18-Heptadecafluorooctadec-9-ynoic acid (2)
To a solution of 7 (580 mg, 1.01 mmol) in acetone (6 mL)
was added the Jones reagent at room temperature till the
color of the chromium ion remained visible for 10 min. The
mixture was quenched with 2-propanol. After filtration and
evaporation of the solvent, the residue was extracted with
EtOAc. The organic layers were washed with satd NaCl aq,
and then dried over MgSO4. After filtration and evaporation
of the solvent, the residue was purified by a column
chromatography (EtOAc/n-hexane, 20–30%), and then was
recrystallized in n-hexane at À20 8C to give 11,11,12,
12,13,13,14,14,15,15,16,16,17,17,18,18,18-heptadecafluor-
ooctadec-9-ynoic acid (2) (492 mg, 83.0%).
mp 73.4–78.6 8C. 1H NMR (CDCl3) d: 1.52–1.62 (6H, m,
H4–H6), 1.52–1.62 (2H, m, H7), 1.62–1.69 (2H, m, H3),
2.29–2.44 (2H, m, H8), 2.35 (2H, t, J = 7.46 Hz, H2). 19F
NMR (CDCl3) ppm: À18.00 (3F, t, J = 9.71 Hz, F18),
À33.16 to À33.56 (2F, m, F11), À58.06 to À58.56 (2F, m,
F12), À58.90 to À59.59, À59.59 to À60.36 (4F, 4F, m, m,
F13–F16), À63.06 to À63.58 (2F, m, F17). IR (cmÀ1):
1713.44 (CBC). ESI-MS (m/z): calcd. for C18H15F17O2 [M]+
588.0801, found 588.0797.
3.2.9. 11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,
18,18-Heptadecafluoro-1-tetrahydropyranyloxy-
octadec-9-yne (9) [Scheme 3, route b]
A solution of 8 (1.39 g, 1.77 mmol) in anhydrous Et2O
(16 mL) was added to a solution of t-BuOK (497 mg,
4.43 mmol) in anhydrous Et2O (10 mL) at À20 8C, and this

1964
K. Takai et al. / Journal of Fluorine Chemistry 125 (2004) 1959–1964
3.2.12. 11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,
18,18-Heptadecafluoro-9-iodooctadecan-1-ol (10)
aq, and then dried over MgSO4. After filtration and
evaporation of the solvent, the residue was recrystallized
in n-hexane at À20 8C to give 11,11,12,12,13,13,14,
14,15,15,16,16,17,17,18,18,18-heptadecafluorooctadecanoic
acid (3) (197 mg, 93.3%).
To a solution of 9-decen-1-ol (787 mg, 5.04 mmol) in
CH3CN (5 mL) and deionized H2O (5 mL) was added
perfluorooctyl iodide (3.28 g, 6.00 mmol), NaHCO3
(431 mg, 5.04 mmol) and 85% Na2S2O4 (1.03 g,
5.04 mmol) at 0 8C, and then this mixture was stirred for
4 h at room temperature. The mixture was diluted with
deionized H2O, and then extracted with CH2Cl2. The
organic layers were washed with satd NaCl aq, and then
dried over MgSO4. After filtration and evaporation of
the solvent, the residue was purified by a column chroma-
tography (EtOAc/n-hexane, 30%) to give 11,11,12,12,
13,13,14,14,15,15,16,16,17,17,18,18,18-heptadecafluoro-9-
iodooctadecan-1-ol (10) (2.76 g, 76.2%).
1H NMR (CDCl3) d: 1.24–1.42 (10H, m, H4–H8), 1.53–
1.70 (4H, m, H3, H9), 1.98–2.12 (2H, m, H10), 2.35 (2H, t,
J = 7.46 Hz, H2). 19F NMR (CDCl3) ppm: À18.00 (3F, t,
J = 12.91 Hz, F18), À51.65 (2F, m, J = 17.38 Hz, F11),
À58.99 (2F, bs, F12), À59.10 to À59.70, À60.03 to À61.35
(4F, 2F, 2F, m, m, m, F13–F16), À62.75 to À63.80 (2F, m,
F17). ESI-MS: (m/z) calcd. for C18H19F17O2 [M]+ 590.1113,
found 590.1114.
3.2.15. Equilibrium spreading pressure measurements
A fatty acid sample was sprinkled onto the clean surface
of pure water (pH ꢀ6) in a thermostated Teflon vessel as one
or more visible droplets or powders remained on the surface.
The surface pressure was monitored by Wilhelmy technique
using a sandblasted platinum plate attached to a KSV
electronic balance (pressure sensitivity: 0.01 mN/m; KSV
Instruments, Helsinki, Finland) at 25.0 Æ 0.2 8C. This set-up
was housed in a clean box to reduce any contaminations. The
equilibrium spreading pressures, pes were reproduced
within Æ0.5 mN/m.
1H NMR (CDCl3) d: 1.16–1.48 (10H, m, H3–H7), 1.48–
1.68 (2H, m, H2), 1.70–1.90 (2H, m, H8), 2.68–2.83, 2.83–
3.00 (1H, 1H, m, m, H10), 3.65 (2H, t, J = 6.71 Hz, H1),
4.33 (1H, tt, J = 4.41, 8.88, 17.60 Hz, H9). 19F NMR
(CDCl3) ppm: À18.03 (3F, t, J = 9.71 Hz, F18), À48.25 to
À48.78, À49.20 to À49.74, À51.00 to À51.19, À52.20 to
À52.70 (2F, m, m, m, m, F11), À58.55 to À59.00 (2F, m,
F12), À59.00 to À59.50, À59.75 to À60.28, À60.60 to
À61.20 (4F, 2F, 2F, m, m, m, F13–F16), À63.20 to À63.64
(2F, m, F17).
3.2.13. 11,11,12,12,13,13,14,14,15,15,16,16,17,17,18,
18,18-Heptadecafluorooctadecan-1-ol (11)
References
10 (2.76 g, 3.84 mmol) was added to a mixture of Zn
powder (507 mg, 7.75 mmol) and NiCl2Á6H2O (97.5 mg,
0.77 mmol) in dry THF (5.8 mL) and deionized H2O (10
drops). This mixture was stirred for 4 h at room temperature.
The mixture was quenched with satd NaHCO3 aq, and was
extracted with CH2Cl2. The organic layers were washed with
satd NaCl aq, and then was dried over MgSO4. After
filtration and evaporation of the solvent, the residue was
purified by a column chromatography (EtOAc/n-hexane,
30%) to give 11,11,12,12,13,13,-14,14,15,15,16,16,17,
17,18,18,18-heptadecafluorooctadecan-1-ol (11) (1.54 g,
78.8%).
1H NMR (CDCl3) d: 1.26–1.45 (10H, m, H3–H8), 1.52–
1.65 (4H, m, H2, H9), 2.05 (2H, tt, J = 8.24, 18.87 Hz, H10),
3.65 (2H, tt, J = 4.03, 6.46 Hz, H1). 19F NMR (CDCl3) ppm:
À18.00 (3F, t, J = 10.04 Hz, F18), À51.71 (2F, m,
J = 16.03 Hz, F11), À58.72 to À59.57, À59.79 to
À60.17, À60.65 to À61.10, (6F, 2F, 2F, m, m, m, F12–
F16), À63.20 to À63.36 (2F, m, F17).
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