MC200043A1 - Highly fluorescent ampiphiles with non-ionic hydrophilic spacer: synthesis and applications in the field of surfactants - Google Patents

Description

2

Highly fluorinated amphipaths with non-ionic hydrophilic spacer: synthesis and application in the field of surfactants

Non-ionic surfactants sometimes face problems with water solubility. Three strategies can be considered to increase the hydrophilicity of the molecule while keeping the hydrophobic chain constant:

a) increase the length of the polar chains, Rp(CH2)pO(C2H40)nX

This is the case, for example, with oligooxyethylated compounds [C. Selve, B. Castro, Tetrahedron 39 10 (1981)1313],

_-OH

b) increase the presence of hydrophilic sites, HON^_^r^^^NHCONHC2H4Rir

HO

This is the case, for example, of oligohydroxylated multisite compounds [M.A. Jouani, F. Szonyi, H. Trabelsi, A. Cambon, Bull. Soc. Chim. Fr. m (1994) 173],

/(C^O^H

c) increase the number of polar chains, R^H^N

\c2H40)nH

20 This is the case, for example, of polypod compounds [F. Guittard, E. Taffin de Givenchy, A. Cambon, Tetrahedron Lett. 36 (1995) 7863],

The strategy employed in the present invention could be similar to the first case mentioned previously.

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Perfluoroalkyl molecules possessing a non-ionic hydrophilic group intercalated between two long hydrophobic chains are extremely rare in the literature. To our knowledge, only two examples have been described [E. Bollens, C. Mahieu, US patent 6017547 (2000)][T. Tashiro, K. Iwase, S. Yamada, A. Obayashi, JP patent 322965 (1999)]. The 30 authors claim mixed polyfluorinated compounds with the respective general formulas Rf<CH2)nX[C3H5(OH)]YRH and RfCH2CH(OH)CH2O(C2H4O)nRH, possessing one perfluoroalkyl chain and one hydrocarbon chain. The originality of the synthesized molecules and

3

The advantage presented in this invention lies in the fact that they possess 2 hydrophobic and oleophobic perfluoroalkyl chains. Such molecules could be compared, in their structure (or even in their behavior), to "geminis" [F.M. Menger, 5 J.S. Keiper, Angew. Chem. Int. Ed. 39 (2000) 1906] with the difference that geminis have two charged heads and are therefore part of the class of ionic surfactants.

The present invention relates to the synthesis of entirely original diester-type compounds having a non-ionic, oligooxyethylated hydrophilic core and two partially fluorinated hydrophobic and oleophobic pendant chains positioned at a, c of the polar portion. They can be schematically represented by the following general formula:

O O

II

RF(CH2)3CO(C2H4O)nC(CH2)3RF

15 in which R/r is a perfluorinated chain and in particular Rf = C4F9, C4F13, CSF17 and n is an integer at least equal to 1 and in particular n = 2, 4 and 6

They are prepared from novel acid chloride-type reaction intermediates, Rf(CH2)3COCl (themselves obtained from malonic condensation [N. Mureau, F. Guittard, S. Géribaldi, Tetrahedron Lett. 41 (2000) 2885]) by double condensation on various polyethylene glycols. The present invention can be summarized by the following reaction scheme:

R^(CHo)3COOH —PCls > R^CH^COCl 1/2 >

Step 1 Step 2

la-c o o

25 II II

IV(CH2)3CO(C2H4O)nC(CH2)3R^

Ila-i

In what follows, the operating procedures and the identification of some examples of synthesized compounds are detailed by way of illustration of the present invention but are in no way limiting.

M

synthesis of 4-F-αIκαλλαν ...

In a 50 mL round-bottom flask equipped with a magnetic stirrer and a condenser, under a nitrogen atmosphere, 0.01 moles of acid and 1.1 equivalents of phosphorus pentachloride are placed. The mixture liquefies at room temperature and is then maintained at 70°C for 3 hours. POCI3 is removed at room temperature under vacuum (20 mmHg), and the acid chloride is then purified by distillation. Yields range from 91% to 95%.

identification as an example of the compound CiFc/CHACOCl

JH NMR (CDCI3/TMS) 6 (ppm): 3.05 (t, 2H, 3J = 6.8 Hz); 2.13 (m, 4H).

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synthesis of oligooxidive Ha-i diesters (step 2)

In a 50 mL round-bottom flask equipped with a magnetic stirrer and a condenser, under a nitrogen atmosphere, 4.5 × 10⁻³ moles of polyoxyethyl diol are mixed with 0.01 moles of acid chloride. The reaction mixture is heated to 70°C for 20 h. Excess acid chloride is removed using a Kugelrohr, and the product is then purified by silica gel chromatography (solvent: methanol). Yields range from 97% to 99%.

identification as an example of the compound C JnfCHï^COofCïHjO^COfCHï^CfiEjj ¹H NMR (CD3OD/TMS) ô (ppm): 4.23 (t, 4H, 3J = 4.70 Hz); 3.68 (t, 4H, 3J - 4.70 Hz); 20 3.62 (s, 8H); 2.49 (t, 4H, 3J = 7.15 Hz); 2.25 (m, 4H); 1.91 (m, 4H).

Mass (ESI, positive mode): 705 (100%) [M+Na]+.

The evaluation of surfactant properties is carried out through the study of surface tension curves as a function of the logarithm of concentration (Ys = f(0og) C). These curves (see Figures 1 and 2) allowed the determination of the critical micelle concentrations and corresponding surface tensions for the synthesized compounds (except for compound Ilg, which is insoluble in water). The results are summarized in Table 1. The trends generally observed in the literature for perfluorinated series are a decrease in surface tensions and CMCs with increasing amounts of fluorine-30 in the molecule. When comparing the results obtained for the same number of oxyethyl groups (n = 2), a decrease in Ys is indeed observed with increasing length of the perfluorinated chain. Conversely, the CMC values increase. Similarly, the

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The variations in ys as a function of increasing number n of (C2H4O) motifs (for the same fluorinated chain R/r = C6F13) are unexpected: ys decreases with increasing n, while proportionally, the amount of fluorine decreases. Conversely, the CMC increases when the number n of ethoxylated motifs increases. Nevertheless, these unusual developments are very interesting and constitute an aspect of the present invention.

Table 1: Surfactant properties of oligooxyethylated diesters

No.

IV, n ys (mN.m"1)*

ys (mN.m"1)**

CMC (mol.1'1)

Ha

C4F9, 2

28.5

36.3

2.86.10-5

HD

CÔF 13, 2

26.7

29.3

7 O

00

Hg

C8F17, 2

insoluble (solubility limit < 9.10° mol.l"1)

born

CÔFis, 4

20.6

21.2

4.91.10"4

Hf

C6Fi3, 6

18.5

19.4

9.77.10"4

* Values measured for surfactant concentrations of 0.1% ** Values recorded at the CMC

10

i i 1 1 1 ! log C

0

-7 -6 -5 -4 -3 -2 -1

30

Figure 1: Surface tensions as a function of the logarithm of concentrations for F-hexylated oligooxyethyl diesters

7

20

25

30

Claims (7)

DEMANDS 1) partially fluorinated precursors corresponding to the general formula: R^CHs^COCl in which Rf is a perfluorinated CnF2n+i chain (more particularly R/r is a 5 F-butyl, F-hexylated or F-octylated chain). O O 2) oligooxyethylated diester type compounds of formula: R^Ctb^CO^titO^C^Hh^Rp in which Rf is a perfluorinated CnF2n+i chain (in particular R/r is an F-butyl, F-hexylated or F-octylated chain) and n is an integer at least equal to 1 (in particular n is 2, 4 or 6). 3) method of manufacturing the compounds according to claims 1 and 2 described in the present invention. 15 4) application of the compounds according to claim 1 as reaction intermediates. 5) application of the compounds according to claim 1 in the synthesis of highly fluorinated surfactants for the formation of organized molecular structures (liquid crystals, vesicles, emulsions, microemulsions). 6) application of the compounds according to claim 2 as surfactants. 7) application of the compounds according to claim 2 as an agent usable in A3 F (floating film forming agents) and in blood substitute formulations. y J