Synthesis and self-assembling behavior of F-amphiphilic functionalized amines

Article abstract of DOI:10.1016/j.jfluchem.2011.03.019

A simple route to fluoroalkylated functionalized secondary amines is proposed by the treatment of 2-perfluoroalkylprop-2-enoic acids with various primary amines. Two of these compounds were obtained from oxyethylenic diamine and present an amphiphilic str

Full text of DOI:10.1016/j.jfluchem.2011.03.019

Journal of Fluorine Chemistry 134 (2012) 115–121
Contents lists available at ScienceDirect
Journal of Fluorine Chemistry
journal homepage: www.elsevier.com/locate/fluor
Synthesis and self-assembling behavior of F-amphiphilic functionalized amines
a
a
a
b
a,
*
´
Nicolas Dupuy , Andreea Pasc , Estelle Mayot , Sedat Cosgun , Christine Gerardin-Charbonnier
a LERMaB, EA 4370, IFR 110, Faculte´ des Sciences et Technologies, Universite´ Henri Poincare´, Nancy, BP 70239, 54506 Vandoeuvre-le`s-Nancy, France
b Department of Chemistry, Fatih University, Istanbul, Turkey
A R T I C L E I N F O
A B S T R A C T
Article history:
A simple route to fluoroalkylated functionalized secondary amines is proposed by the treatment of 2-
perfluoroalkylprop-2-enoic acids with various primary amines. Two of these compounds were obtained
from oxyethylenic diamine and present an amphiphilic structure.
Received 13 January 2011
Received in revised form 22 March 2011
Accepted 27 March 2011
Available online 1 April 2011
These compounds exhibit an excellent surface activity since they are lowering the surface tension to
18–20 mN/m and this, at very low concentrations (around 10ꢀ5 M). DLS measurements and TEM studies
show an original behavior of the monocatenar fluorinated surfactants 5n and 5o, which are able to
spontaneously self-assembles into vesicles, and therefore it makes them suitable candidates as carriers
in drug or gene delivery systems.
Keywords:
Imines
Perfluoroalkylated secondary amines
Fluorocarbon surfactant
Hybrid amphiphiles
Spontaneous vesicles
ß 2011 Elsevier B.V. All rights reserved.
1. Introduction
carbonyl compounds [14–16]. For some of these methods, the
difficulty is to avoid the deshydrofluorination. Secondary amines
Inthefield ofbioactivemolecules, fluoroorganiccompounds have
received a great deal of attention and many studies showed that the
incorporation of one, two, three or several F atoms into an organic
compound modify its physical, chemical and biological properties
[1–6]. Their properties make them suitable for various applications
in organic synthesis, medicinal chemistry, plant health chemistry, as
well as in material science. Perfluoroalkylated amphiphilic com-
pounds are excellent emulsifiers for water colloidal systems, i.e.
microemulsions or vesicles. They have been proposed as biocom-
patible surfactants in medical area. Perfluorocarbon emulsions can
thus be used for drug deliverysystems, vaccines, or genes [7,8]. Some
of them have been proposed as biocompatible oxygen carriers, for
example, in storage of tissues and organs or in cell culture. In general,
they are functionalized with a variety of structures including sugars,
amino acids, pseudo-peptides, etc. [9–12].
are more difficult to be obtained. Previous syntheses of
fluorinated amines are relatively few and include Mitsunobu
reaction [17], hydroamination of in situ generated arylacetylenes
[9], reaction of perfluoroalkyl Grignard reagents with N(a-
aminoalkyl)benzotriazole) [18], or boron trifluoride reaction of
perfluoroalkyllithiums with imines [19,20]. In this context, we
propose a simple pathway to these compounds by heating a
mixture of modified commercial perfluoroalkylethanols and a
primary amine. Two of these compounds, 5n and 5o, exhibit
particular amphiphilic properties, and their self-assembling
properties are underlined.
2. Results and discussion
2.1. Synthesis
A specific interest has been focused on the development of
synthetic methods for the preparation of fluorinated building
blocks as synthons for functionalized fluorocarbon molecules.
Among them, fluorinated amines are of interest as scavengers or
precursors in the synthesis of fluorinated molecules or catalysts
[13]. The synthesis of perfluoroalkylated primary amines has
been developed by several methods such as the Gabriel method,
the azido derivatives, reductive amination of fluorine-containing
We showed, in previous work, the reactivity of ester derivatives
of 3-fluoro-3-fluoroalkylpropenoic acids with different nucleo-
philes such as alcoholates, amines, azides, affording to acetals, enol
ethers and enamines [21–25].
Since the corresponding acids can also directly react with
primary amines [26], this kind of reaction could be extended to
functionalized amines (amino acids, hydrophilic amines) in order
to further label the molecules with additional functionalities.
Unsaturated acids were prepared as previously reported by our
group, from commercially available 2-perfluoroalkylethanols, by
oxidation with chromic acid and dehydrofluoration with aqueous
NaOH [27]. In contact with a primary amine in refluxing toluene,
* Corresponding author. Tel.: +33 3 83 68 43 32; fax: +33 3 83 68 43 22.
E-mail address: Christine.Gerardin@lermab.uhp-nancy.fr
(C. Ge´rardin-Charbonnier).
0022-1139/$ – see front matter ß 2011 Elsevier B.V. All rights reserved.
doi:10.1016/j.jfluchem.2011.03.019

116
N. Dupuy et al. / Journal of Fluorine Chemistry 134 (2012) 115–121
Scheme 1. Reactivity of 3-fluoro-3-fluoroalkylpropenoic acids with primary amines.
Scheme 2. Proposed mechanism of the imine formation.
these perfluoroalkylated acids lead after decarboxylation to imines
(Scheme 1).
The reaction is efficient with all tested primary amines and the
yields are higher than 80% even with sterically hindered amines
such as the amino acids (Table 1).
The reduction of imines 4a–h and 4m–o by hydrogen with
palladium on charcoal needed a high pressure and a moderated
temperature (Scheme 3). Secondary amines 5 have been obtained
with excellent overall yields. Compounds 5a–d are interesting
building blocks for hybrid surfactants with a fluorocarbon and a
The proposed mechanism is described in Scheme 2. After the
acid–base reaction between the fluorinated acid 2 and the
triethylamine, the vinylic fluorine can be substituted by the R-
NH2 amine, certainly in two steps mechanism: Michael addition
and elimination of fluoride. The formed enamine is then
participating as proton donor to catalyze the decarboxylation.
The imine is obtained by tautomerism from the enamine.
Table 1
Yields of formation and reduction of imines.
Series
n
R
Yield 4
Yield 5
a
b
c
d
e
f
4
6
4
6
4
6
4
6
4
6
8
6
6
6
8
–(CH2)5CH3
84
90
92
80
83
82
75
83
82
77
81
86
93
83
85
68
70
72
85
/
–(CH2)5CH3
–(CH2)7CH3
Scheme 3. Reduction of the imines.
–(CH2)7CH3
–CH2C6H5
–CH2C6H5
/
g
h
i
–CH2CH2OH
73
78
92
94
91
/
–CH2CH2OH
–CH(COOEt)(CH2)4NHZ
–CH(COOEt)(CH2)4NHZ
–CH(COOEt)(CH2)4NHZ
–CH2C6H4OMe
–CH(CH2Ph)COOMe
–(CH2CH2O)2(CH2)2NH2
–(CH2CH2O)2(CH2)2NH2
j
k
l
m
n
o
70
90
70
Scheme 4. Reduction of the benzylic imines.

N. Dupuy et al. / Journal of Fluorine Chemistry 134 (2012) 115–121
117
Scheme 5. Reduction of imine from protected lysine.
hydrocarbon chain, and 5m allows to envisage the introduction of
an N-perfluoroalkylated amino acid in a peptide (Scheme 4).
In the case of benzylic imines (4e, 4f, 4l), primary amines are
directly obtained because of simultaneous hydrogenolysis of
benzylic group.
As for the lysine derivatives, hydrogenolysis of N-protecting
group benzyloxycarbonyl occurs at the same time as the
hydrogenation of the imine with Nickel Raney (Scheme 5).
The minimal surface tension reaches a plateau at 20 and 18 mN/
m, respectively in water and in buffer solution and this value seems
to be independent of the length of the perfluorinated chain.
However, when increasing the F-tag length the CAC values
decrease in agreement with what is usually observed for
surfactants. Also, the CAC values are higher in buffer solution
than pure water. At this pH, the lipid is cationic (the primary amine
is protonated). Usually, the addition of salt compresses the double
electric layer of the polar head of ionic surfactants. This can
produce a screening of the electrostatic repulsions between
neighboring hydrophilic groups and, therefore, enables the
aggregation to a lower surfactant concentration.
N(a)-perfluoroalkylated lysine is obtained with excellent yield.
2.2. Amphiphilic properties of compounds 5n and 5o
Surface tension measurements of aqueous solutions of 5n and
5o were realized in pure water and in TRIS buffer (pH = 7.4) in
order to determine the critical aggregative concentration (CAC)
(Fig. 1). The results gathered in Table 2 show the CAC and the
minimal surface tension values. Moreover, surface tension
measurements allowed us to estimate the mean surface area
per molecule, A, of the absorbed non ionic surfactant, from the
The estimated molecular area in pure water, 34 (5n) and 32
2
˚
(5o) A , respectively are slightly higher than the cross section area
2
˚
of the fluoroalkyl chain (27–30 A ). Thus, the molecular area at the
interface seems to be governed by the contribution of both
fluorinated and ethylene oxide segments, which are slightly tilted
with respect to the normal at the interface (Fig. 1d). This might be
due (i) to the stiffness of the fluorinated chain and the absence of
the any ‘‘gauche’’ defects and (ii) to the flexibility to the
ethylenoxide moiety. In addition, area per molecules are higher
inverse of the surface excess concentration,
according to the Gibbs equation, Fig. 1c).
G (calculated
Fig. 1. Surface tension measurements of 5n and 5o (a) in pure water and (b) in TRIS buffer (pH 7.4). Equations of the estimated molecular area and Gibbs surface excess (c).
Suggested self-assembled Gibbs layer of molecular modeled fluorinated surfactant 5o as with MOPAC method, CS Chem Office (d).

118
N. Dupuy et al. / Journal of Fluorine Chemistry 134 (2012) 115–121
2
Table 2
˚
in buffer solution, 38 (5n) and 42 (5o) A , respectively, which could
be due to the electrostatic repulsions between the ethylenoxide
moieties and the phosphate anions.
Amphiphilic properties of 5n and 5o as determined by surface tension
measurements.
2
CAC (mol lꢀ1
)
Area per molecule (A )
g(CAC)
(mN mꢀ1
˚
Compound
DLS measurements were carried out on 1 mM solutions of 5n
and 5o, respectively in pure water and in buffer solutions and the
hydrodynamic size and the polydispersity of the aggregates were
determined. In all cases, the measurements show two populations,
centered on around 60–70 nm and 200–360 nm (Table 3),
depending on surfactant chain length and on the aqueous solution,
and these aggregates were stable at room temperature for at least
48 h. Moreover, TEM micrographs allow us to visualize these
aggregates (Fig. 2e and f).
)
5n/water
5o/water
5n/buffer
5o/buffer
6 ꢁ 10ꢀ5
2 ꢁ 10ꢀ5
3 ꢁ 10ꢀ5
6 ꢁ 10ꢀ6
34
32
38
42
20
20
18
18
Table 3
Thus, 5n and 5o have the ability to spontaneously self-assemble
into vesicles in aqueous solutions, which is rare for monocatenar
surfactants. Indeed, to date, only several examples are reported in
the literature [7,8,28–30]. This phenomenon seems to be related to
the particular features of fluorinated chains and to the asymmetry
of the molecule [31–35].
Hydrodynamic diameter values of 5n and 5o as determined by DLS measurements
in water and in buffer solution, respectively.
Compound
Hydrodynamic diameter
(nm) in pure water
Hydrodynamic diameter
(nm) in buffer solution
5n
5o
65 and 220–300
70 and 300–360
60 and 200–230
65 and 275
Fig. 2. DLS measurements of 1 mM solution of (a) 5n in water, (b) 5o in water, (c) 5n in buffer, (d) 5o in buffer, respectively show two populations of aggregates centered on
50 nm and 300 nm. TEM micrographs of (e) 5n and (f) 5o in water show vesicles of around 70 and 300 nm.

N. Dupuy et al. / Journal of Fluorine Chemistry 134 (2012) 115–121
119
3. Conclusion
For 4e, yield 83%; Anal. Calcd for C14H10F11N: C, 41.91; H, 2.51.
Found: C, 41.50; H, 2.85.
We reported in the present work the synthesis of novel
fluorinated/hydrogenated secondary amines starting from com-
mercially available fluorinated acids and a variety of primary
hydrogenated amines, in a very simple and efficient method. In the
key step, the Michael addition of the hydrogenated amine followed
by the elimination of the vinylic fluorine was proposed as a
possible mechanism.
By using diamino-diethyleneoxide, two amphiphilic com-
pounds, 5n and 5o, were prepared and they exhibit excellent
surface activity (minimal surface tension of 18–20 mN/m) and low
critical concentration aggregation (around 10ꢀ5 M). By combining
a rigid fluorinated hydrophobic tag responsible for self-assembling
and a flexible ethylenoxide moiety sufficiently hydrophilic so that
the compound could be soluble at high concentration (up to
1 mM), one can design original monocatenar lipids, which are able
to spontaneously form vesicles in water.
2-(3,3,4,4,5,5,6,6,7,7,7-undecafluoroheptan-2-ylideneamino)etha-
nol, 4g (n = 4), 4h (n = 6), yellow liquid, IR (KBr) 1300–
1100 cmꢀ1 C–F); 1H NMR (CDCl3) 2.10 (s, 3H, CH3) 3.20 (m,
(n
2H, –CH2CH2OH) 3.900 (m, 2H, –CH2CH2OH); 13C NMR (CDCl3):
22.7(CH3C55N) 47.4(C55NCH2) 68.5(CH2OH) 110–120(CF); 19F NMR
(CDCl3) ꢀ80.7(t, 3F, CF3); ꢀ116 to ꢀ124(m, 2F, CF3(CF2)3CF2C55N);
ꢀ122 to ꢀ128(m, 6F, CF3(CF2)3CF2C55N). For 4g, yield 75%, Anal.
Calcd for C13H16F11N: C, 39.50; H, 4.08. Found: C, 39.90; H, 3.95.
Ethyl-6-(benzyloxycarbonylamino)-2-(perfluoroalkanan-2-ylide-
neamino)hexanoate, 4i (n = 4), 4j (n = 6), 4k (n = 8), yellow liquid, IR
(KBr) 3350 cm
(
ꢀ1 nN–H); 1730 cmꢀ1
(n
C55O ester); 1715 cmꢀ1
(nC55O carbamate);1300–1100 cm (
ꢀ1 nC–F); 1H NMR (CDCl3): 0.9–
1.2(m, 7H, CH3 and NHCH2(CH2)2CH2 lysine) 1.42(m, 2H,
NHCH2(CH2)2CH2 lysine) 1.83(m, 3H, CH3) 3.07(m, 2,
NHCH2(CH2)2CH2 lysine) 4.05(m, 2H, COOCH2CH3) 4.66(m, 1H, CH
lysine) 4.97(m, 2H, CH2C6H5) 7.23(m, 5H, C6H5). 13C NMR (CDCl3):
This property makes them interesting candidates for biomedi-
cal applications, such as novel drug or gene carriers. This could be a
new approach in the study of oligonucleotide/surfactant interac-
tions, with respect to the communily used hydrogenated mono-
catenar surfactant-made micells or bicatenar surfactant-fabricated
vesicles.
16.16
(COOCH2CH3)
26.72(CH2(CH2)2CH2NHZ)
31.61(CH2
(CH2)2CH2NHZ) 42.18(CH2(CH2)2CH2NHZ) 62.27(CHCH2(CH2)2CH2
NHZ) 60.24(COOCH2CH3) 66.60(NHCOOCH2C6H5) 106–120(CF) 128
and 136.20 (C6H5) 155.07(C55N) 168.10(COOCH2CH3); 19F NMR
(CDCl3) ꢀ81.08(t, 3F, CF3); ꢀ116(s, 2F, CF3(CF2)nꢀ1CF2C55N); ꢀ121.49
to ꢀ126.52(m, 2n–2F, CF3(CF2)nꢀ1CF2C55N). For 4i, yield 82%, Anal.
Calcd for C23H25F11N2O4: C, 45.85; H, 4.18. Found: C, 45.10; H, 3.90.
1-(4-methoxyphenyl)-N-(3,3,4,4,5,5,6,6,7,7,7-undecafluorohep-
tan-2-ylidene)methanamine, 4l, yellow liquid, IR (KBr) 1300–
4. Experimental
4.1. Synthesis
1100 cmꢀ1 C–F); 1H NMR (CDCl3):1.90(s, 3H, CH3) 3.70(s, 3H,
(n
C6H4CH3) 6.70(dd, 4H, C6H4). 13C NMR (CDCl3): 15.4(CH3C55N)
55.4(CH3O) 110–120(CF) 114.7–157.9 (Aromat) 158.5(C55N) Yield
83%. Anal. Calcd for C15H12F11NO: C, 41.78; H, 2.80. Found: C,
42.20.10; H, 2.90
All solvents were reagent grade and used without further
purification. The progress of reaction was determined using FT-IR
spectra. NMR spectra were recorded on a Bruker AM 400 or an AC
200 instrument. Chemical shifts are reported in ppm relative to
Methyl-3-phenyl-2-(3,3,4,4,5,5,6,6,7,7,7-undecafluoroheptan-2-
ylideneamino) propanoate, 4m, yield %, yellow liquid, IR (KBr)
1300–1100 cmꢀ1(C–F); 1740 (C55O); 1H NMR (CD3OCD3): 1.80(s,
3H, CH3) 3.20(dd, 2H, CH2C6H5) 3.70(s, 3H, COOCH3) 4.70(m, 1H,
CH Phenylalanine) 7.20(m, 5H, C6H5). 19F NMR (CD3OCD3):
ꢀ80.7(t, 3F, CF3) ꢀ116(m, 2F, CF3(CF2)5CF2C55N) ꢀ122 to
ꢀ128(m, 10F, CF3(CF2)5CF2C55N) Yield 93%. Anal. Calcd for
TMS as internal standard for the 1H spectra and to CFCl3 for the 19
F
spectra. Coupling constants (J) are in Hertz. IR spectra were
recorded on a Perkin-Elmer FTIR ‘‘spectrum one’’ in ATR mode or
transmission mode. Melting points were made on Kofler Bench and
were not corrected. Elemental analyses were performed by
C.N.R.S-Vernaison or at UHP on Thermofinnigan FlashEA 1112.
3-Fluoroalkyl-3-fluoro-2-enoic acids were synthesized from alco-
hol as method described [21].
C17H12F15NO: C, 38.43; H, 2.28. Found: C, 38.20.10; H, 2.50.
4.1.2. Synthesis of imines 4n–o
4.1.1. Synthesis of imines 4a–m
A mixture of 1 g of 3-fluoroalkyl-3-fluoro-2-enoic acid, 10 eq. of
2,20-(ethylenedioxy)bis(ethylamine) and 30 eq. of Et3N, in 150 mL
of toluene was heated to reflux for 24 h. Toluene and excess of Et3N
were then removed under vacuum and the resulting mixture was
re dissolved in ether and solution was filtrated. The filtrate was
washed 6 times with 100 mL of water. Organic phase was dried on
MgSO4 and the solvent evaporated. Final products were sufficient-
ly pure.
2-(2-(2-aminoethoxy)ethoxy)-N-(perfluoroalkan-2-ylide-
ne)ethanamine, 4n (n = 4), 4o (n = 6). Yellow liquid, IR (KBr)
1300–1100 cmꢀ1 (C–F); 1682 cmꢀ1 (C55N); 1H NMR (CDCl3):
1.29(m, 2H, NH2) 2.02(s, 3H, CH3) 2.83(m, 2H, CH2NH2) 3.46(t,
2H, CH2N = C, 3J = 4 Hz) 3.56–3.96(m, 8H, CH2O). 13C NMR
(CDCl3): 14.33(CH3C55N) 42.17(CH2NH2) 52.71(C55NCH2)
71.06–73.92 (CH2O) 106–120(CF) 159.40(C55N). 19F NMR
(CDCl3): ꢀ81.22(t, 3F, CF3) ꢀ116.19(m, 2F, CF3(CF2)nꢀ1CF2C55N)
N) ꢀ122 to ꢀ128(m, 2n–2F, CF3(CF2)nꢀ1CF2C55N). 4n Yield 83%.
Anal. Calcd for C15H17F15N2O2: C, 33.22; H, 3.16. Found: C,
32.850.10; H, 3.13
A mixture of 1 g of 3-fluoroalkyl-3-fluoro-2-enoic acid, 1.1 eq. of
amine (or lysine with appropriate protections) in 150 mL of toluene,
was heated to reflux for 24 h (36 h in case of 4m). Toluene was then
removed under vacuum and the resulting mixture was redissolved
in ether and the solution was filtrated. The filtrate was washed with
100 mL of aqueous HCl and saturated solution of sodium chloride
until neutralization. Organic phase was dried on MgSO4 and the
solventwasevaporated. Finalproductswerenot purified (purity95–
98% according to NMR).
N-(perfluoro-alkan-2-ylidene)alkyl-1-amine, 4a (n = 4, n0 = 4),
4b (n = 6, n0 = 4), 4c (n = 4, n0 = 6), 4d (n = 6, n0 = 6), yellow
liquids, IR (KBr) 1300–1100 cmꢀ1 (C–F); 1H NMR (CDCl3) 0.90 (t,
3
3H, –CH2(CH2)nꢀ2CH3, JHH = 7 Hz), 1.30–1.80 (m, 2n0H,
–
0
0
CH2(CH2)n CH3); 2.00 (s, 3H, CH3); 3.50 (t, 2H, –CH2(CH2)n CH3,
3JHH = 7 Hz); 19F NMR (CDCl3) ꢀ80.7 (t, 3F, CF3); ꢀ117 (m, 2F, CF3
(CF2)nꢀ1CF2C55N); ꢀ122 to ꢀ128 (m, 2nꢀ2F, CF3(CF2)nꢀ1
CF2C55N). For 4a, yield 84%; Anal. Calcd for C13H16F11N: C,
39.50; H, 4.08. Found: C,39.80; H, 3.90.
1-phenyl-N-(perfluorofluoroalkan-2-ylidene)alcanamine,
(n = 4), 4f (n = 6), yellow liquid, IR (KBr) 1300–1100 cmꢀ1
1H NMR (CDCl3) 2.10 (s, 3H, CH3); 4.70 (s, 2H, –CH2C6H5) 7.30 (m,
5H, C6H5); 19F NMR (CDCl3) ꢀ80.5 (t, 3F, CF3); ꢀ117 (m, 2F,
CF3(CF2)nꢀ1CF2C55N); ꢀ122 to ꢀ128 (m, 6F, CF3(CF2)nꢀ1CF2C55N).
4e
C–F);
(
n
4.2. Reduction of imines
5 mmol of imine dissolved in 45 mL MeOH and catalytic
amount of Palladium 10% on activated carbon, were introduced in a

120
N. Dupuy et al. / Journal of Fluorine Chemistry 134 (2012) 115–121
hydrogenation reactor working under 80 bar H2. After 16 h at 50 8C,
the mixture was cooled down to room temperature, purged with N2
and filtered on celite. The solvent was then removed under vacuum
and the final product was used without further purification.
N-alkyl(1-perfluoroalkyl-ethyl)amine 5a (n = 4, n0 = 4), 5b (n = 6,
n0 = 4), 5c (n = 4, n0 = 6), 5d (n = 6, n0 = 6) Yellow liquid, IR (KBr)
Zetasizer 3000 Has (Malvern Instruments Ltd.) with a light source
He–Ne laser (wavelength 633 nm). The scattering angle was 908.
All solutions were filtered in nanopure water or in buffer solution
before any measurement (filter 450 nm) and all the measures were
carried out at 20 8C.
1300–1100 cmꢀ1(C–F); 1H NMR (CDCl3):0.90(t, 3H,
–
4.5. Transmission electron microscopy
0
0
0
CH2(CH2)n CH3) 1.30(m, (2n + 3)H, –CH2(CH2)n CH3 and CH–CH3)
2.70(m, 2H, –CH2(CH2)n CH3) 3.30(m, 1H, CH–CH3). 13C NMR
0
TEM studies were performed using a Philips CM20 type
microscope at 200 keV. Samples for TEM were prepared by the
negative-staining technique with a 2% sodium phosphotungstate
solution buffered at pH 7.4. A drop of the sample solution was left
on the carbon-coated copper grids for 1 min. Then, excess liquid
was sucked away with a filter paper. Then, a drop of sodium
phosphotungstate solution was left on the cooper grid for 1 min
and the excess liquid was sucked away with a filter paper.
(CDCl3):
13.9(CF2CHCH3)
14.8(NHCH2(CH2)nCH3)
24.1(NHCH2(CH2)nCH3) 33.4(NHCH2(CH2)nCH3) 56(CF2CHCH3)
110–120(CF) 5a Yield 68%. Anal. Calcd for C13H18F11N: C, 39.30;
H, 4.57. Found: C,39.90.10; H, 4.90.
2-(1-perfluoroalkyl-ethylamino)ethanol 5g (n = 4), 5h (n = 6),
yellow liquid, IR (KBr) 1300–1100 cmꢀ1(C–F); 1H NMR
(CDCl3):1.35(m, 3H, CH–CH3) 2.95(m, 2H, CH2OH) 3.65(m, 2H,
CH2NH). 5g Yield 73%. Anal. Calcd for C9H10F11NO: C, 30.27; H,
2.82. Found: C, 30.67.10; H, 3.20.
Research topics
Ethyl 6-amino-2-(1-perfluoroalkyl-ethylamino)hexanoate 5i
(n = 4), 5j (n = 6), 5k (n = 8), yellow liquid, IR (KBr)
Our group is interested for more than twenty years in the
synthesis and the physico-chemical characterization of fluorocar-
bon amphiphilic compounds. Different studies relative to the
design and synthesis of F-amphiphilic compounds with specific
properties (antibacterial, antioxidant, metal binding, antiviral. . .)
have been investigated. We have described methodological
developments for the synthesis of fluorocarbon and hybrid
fluorocarbon/hydrocarbon series to produce molecular tailored
amphiphiles for applications in the fields of drug or gene delivery,
cosmetics, detergency, complexation. We have also developed
access to different kinds of amphiphiles: fluorinated lipopeptides
or peptidoamines analogues, triazoles and various original
hydrophobic parts for surfactants. Specific characterization
techniques for Langmuir monolayers, micelles, vesicles, hydrogels
have been used and correlation between molecular structure and
amphiphilic properties have been established. We have been also
interested from some years ago on wood surface treatment with
fluorinated compounds for hydrophobation purposes in order to
limit its affinity for water and reduce its susceptibility to decay.
3350 cmꢀ1 N–H); 1732 cmꢀ1 C55O ester); 1300–1100 cmꢀ1
(n (n
(n
C–F); 1H NMR (CDCl3): 1.09–1.43(m, 8H, NH–CH–CH3 and –
COOCH2CH3 and H2NCH2CH2CH2CH2CH) 2.01(m, 4H, H2NCH2
CH2CH2CH2CH) 2.69(m, 2H, NH2) 3.18–3.38(m, 4H, NH–CH–CH3,
and CH–COOEt and CH2NH2) 4.08(q, 2H, –COOCH2CH3). 13C NMR
(CDCl3): 14.59(CF2CHCH3 and COOCH2CH3) 20.75–31.28(CH
(CH2)3CH2NH2) 40.78(CH(CH2)3CH2NH2) 51.69(CH(CH2)3CH2NH2)
58.65(CF2CHCH3) 60.24(COOCH2CH3) 106–120(CF) 170.11
(COOCH2CH3) 5i Yield 92%. Anal. Calcd for C15H21F11N2O2: C,
38.31; H, 4.50. Found: C, 38.20; H, 4.90.
Methyl 3-phenyl-2-(1-perfluoroalkyl)amino-propanoate 5m, yel-
low liquid, IR (KBr) 3350 cmꢀ1
(n
N–H); 1740 cmꢀ1
(
n
C55O ester);
1300–1100 cmꢀ1 C–F); 1H NMR (CDCl3): 1.30(d, 3H, NH–CH–
(n
CH3) 2.90(m, 2H, –CH2C6H5) 3.20(m, 1H, CH–COOCH3) 3.70(m, 4H,
NH–CH–CH3, and COOCH3) 7.20(m, 5H, –CH2C6H5). 13C NMR
(CDCl3):15.1(CF2CHCH3)
40.6(CH2Ph)
52.1(COOCH3)
62.8(CHCOOCH3) 66.4(CF2CHCH3) 110–120(CF) 127–137(Aromat)
175.6(COOCH3). Yield 70%. Anal. Calcd for C17H16F11NO2: C, 42.96;
H, 3.39. Found: C, 42.20; H, 3.90.
N-(2-(2-(2-aminoethoxy) ethoxy)ethyl)-(1-perfluoroalkyl)ethyl-
2-amine 5n (n = 4), 5o (n = 6) yellow liquid, IR (KBr)
(n (n
3375 cmꢀ1 N–H); 1300–1100 cmꢀ1 C–F); 1H NMR (CDCl3):
Acknowledgments
EM and ND thank the French Ministry of further Education and
Research for their PhD grant. Authors thank the ministry for the
European Foreign affairs (MAEE) and of Higher Education and
Research (MESR) (Hubert Curien Program ‘‘Bosphore’’) for financial
support, J. Ghanbaja for TEM micrographs, S. Parant for support in
1.25(d, 3H, NH–CH–CH3, 3J = 6 Hz) 2.81(m, 4H, –CH2NH2 and –
CH2NH) 3.36(m, 1H, CH–NH) 3.59(m, 8H, –CH2O) 4.07(m, 3H, NH
and NH2). 13C NMR (CDCl3): 14.56(CF2CHCH3) 40.36(CH2NH2)
50.37(NHCH2) 55.90(CF2CHCH3) 70.99(CH2O) 105–120(CF). 5n:
Yield 90%. Anal. Calcd for C15H19F15N2O2: C, 33.10; H, 3.52. Found:
C, 32.86; H, 3.37.
`
DLS measurements and P. Lemiere for synthesis.
1-perfluoroalkylethylammonium chloride 6a (n = 4), 6b (n = 6), IR
References
(KBr) 3350 cmꢀ1 N–H); 1300–1100 cmꢀ1 C–F); 1H NMR
(n (n
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CH3). 6a: Yield: 60%. Anal. Calcd for C7H7ClF11N: C, 24.05; H, 2.02.
Found: C, 23.85; H, 1.98.
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