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