Synthesis and surface-active properties of a series of new anionic gemini compounds

Article abstract of DOI:10.1016/S0009-3084(99)00003-1

The synthesis of a series of new anionic dimeric amphiphiles 1-5 is described. The CMC and both static and dynamic surface tensions have been measured using the Wilhelmy plate technique and the maximum bubble pressure method. Results are compared to those obtained with the corresponding monomeric surfactants and relevant monomeric or dimeric compounds described in the literature. The relationship between the structural features of the different compounds and their properties is discussed. In particular an increase in the length of the connecting group between the two lipophilic chains lowers the CMC of the compounds which is different from results reported in the literature for other gemini compounds. Copyright (C) 1999 Elsevier Science Ireland Ltd.

Full text of DOI:10.1016/S0009-3084(99)00003-1

Chemistry and Physics of Lipids
99 (1999) 21–32
Synthesis and surface-active properties of a series of new
anionic gemini compounds
Philippe Renouf a, Dominique Hebrault b, Jean-Roger Desmurs b,
Jean-Michel Mercier c, Charles Mioskowski a, Luc Lebeau a,*
a Uni6ersite´ Louis Pasteur-Laboratoire de Synthe`se Bioorganique associe´ au CNRS 74, route du Rhin-BP 24, 67401 Illkirch, France
b Rhoˆne-Poulenc Industrialisation-CRIT-Carrie`res 85, a6enue des Fre`res Perret-BP 62, 69192 Saint-Fons Cedex, France
c Rhoˆne-Poulenc-Centre de Recherche d’Auber6illiers, 52, rue de la Haie-Coq, 93308 Auber6illiers, France
Received 17 September 1998; received in revised form 23 December 1998; accepted 05 January 1999
Abstract
The synthesis of a series of new anionic dimeric amphiphiles 1–5 is described. The CMC and both static and
dynamic surface tensions have been measured using the Wilhelmy plate technique and the maximum bubble pressure
method. Results are compared to those obtained with the corresponding monomeric surfactants and relevant
monomeric or dimeric compounds described in the literature. The relationship between the structural features of the
different compounds and their properties is discussed. In particular an increase in the length of the connecting group
between the two lipophilic chains lowers the CMC of the compounds which is different from results reported in the
literature for other gemini compounds. © 1999 Elsevier Science Ireland Ltd. All rights reserved.
Keywords: Amphiphiles; Critical micelle concentration; Dimeric surfactants; Dynamic surface tension; Synthesis
1. Introduction
monomers, gave rise to the molecular design of
new amphiphiles far removed from the classical
concept that a surfactant is made of one lipophilic
moiety and one polar head connected together
(Nusselder and Engberts, 1989; Cheng et al.,
1992; Stein and Gellman, 1992; Wassermann et
al., 1992; Menger and Littau, 1993; Menger and
Yamasaki, 1993; Perez et al., 1996; Schmidt and
Jankowski, 1996). Thus a considerable number of
investigations have been reported on the surface
During the last decade, the discovery of im-
proved surface-active properties of dimeric (gem-
ini) surfactants, when compared to amphiphilic
Abbre6iations: b, broad; d, doublet; m, multiplet; q, quintu-
plet; s, singlet; t, triplet.
* Corresponding author. Tel.: +33-3-88676857; fax: +33-
3-88678891.
E-mail address: lebeau@aspirine.u-strasbg.fr (L. Lebeau)
0009-3084/99/$ - see front matter © 1999 Elsevier Science Ireland Ltd. All rights reserved.
PII: S0009-3084(99)00003-1

22
P. Renouf et al. / Chemistry and Physics of Lipids 99 (1999) 21–32
and aggregation properties of a variety of gemini
surfactants containing two hydrophobic and two
hydrophilic groups in the molecule (Devinski et
al., 1986; Okahara et al., 1988; Menger and Lit-
tau, 1991; Zana et al., 1991; Zhu et al., 1991a;
Masuyama et al., 1992; Rosen et al., 1992;
Menger and Littau, 1993; Song and Rosen, 1996;
Zana et al., 1991) so as to develop new functions
of surfactants or improve their properties.
In this work, we describe the preparation of a
series of new dimeric anionic surfactants and their
surface-active properties in water (Fig. 1). These
compounds contain a flexible hydrophilic linkage
of two different lengths between the hydrophilic
groups. We compare these dimeric surfactants
Fig. 2. Previously described surficants that are compared to
the gemini compounds prepared in this work.
with the related monomeric surfactants and with
other related compounds described in the litera-
ture and try to clarify the relationship between
structural features and the surface-active and ag-
gregation properties (Fig. 2).
2. Results
2.1. Synthesis of the gemini compounds
The synthetic routes to 1–5 are as follows. All
compounds were obtained starting from 1,2-
epoxydodecane. The basic solvolysis of the oxi-
rane
in
benzyl
alcohol
produced
the
b-hydroxyether 6 (Scheme 1). Compound 6 was
then condensed with a-bromodecanoic acid in the
presence of sodium hydride to give 7. The reduc-
tion of the carboxyl group in compound 7 using
lithium aluminium hydride led to a mixture of the
expected compound 8 together with diol 9, result-
ing from partial debenzylation of the protected
hydroxyl group in 8 (Kutney et al., 1970). Com-
plete debenzylation of the latter compound was
Fig. 1. Structure for the anionic gemini compounds synthe-
sized.

P. Renouf et al. / Chemistry and Physics of Lipids 99 (1999) 21–32
23
Scheme 1.
achieved by catalytic hydrogenolysis over Pd/C.
Diol was obtained as mixture of 2
extracts in methanol, isolation of the diesters, and
subsequent hydrolysis produced the two gemini
compounds 1 and 3 in a pure form. The sulfonate
compounds 2 and 4 were directly prepared by
reacting the diols 9 and 12 with propane sultone
and sodium hydride in refluxing dioxane (Suga et
al., 1968; Carrea et al., 1988). The dissymetrical
9
a
diastereomers that are separable by chromatogra-
phy over silica gel. All attempts to achieve the
direct condensation of 6 with the corresponding
secondary methanesulfonate, bromide, or trifl-
uoromethanesulfonate invariably failed to pro-
duce compound 10 (Scheme 2). The condensation
of two molar equivalents of the secondary alcohol
6 with triethyleneglycol bis-methanesulfonyl ester
in refluxing THF provided dibenzyl ether 11
(Scheme 3). Further debenzylation by hydrogenol-
ysis over Pd/C produced the bis-hydroxyl com-
pound 12. Diols 9 and 12 reacted with sodium
hydride and bromoacetic acid in THF to yield the
corresponding bis-carboxylic acid compounds
that could not be purified satisfactorily on silica
gel (Scheme 4). Further esterification of the crude
gemini compound
5
was prepared via
monodebenzylation of 15 (obtained similarly as
11, from diethylene glycol bis-methanesulfonyl es-
ter and 6) into 16 by catalytic hydrogenolysis
(Scheme 5). The hydroxyl function in 16 was
alkylated through reaction of the sodium salt with
an oligomer of polyethyleneglycol methyl ether
methanesulfonyl ester and produced compound
17. Removal of the second benzyl protective
group yielded the hydroxyl compound 18 that was
further transformed into 5 using propane sultone.
Scheme 2.
Scheme 3.

24
P. Renouf et al. / Chemistry and Physics of Lipids 99 (1999) 21–32
Scheme 4.
condensed either with bromoacetic acid or
The monomeric surfactants 21 and 22 corre-
propane sultone to provide 21 or 22, respectively.
sponding to the gemini compounds were prepared
as well (Scheme 6). The secondary hydroxyl group
in 6 was alkylated using methyl iodide. Debenzy-
lation of the resulting methoxy benzylether 19
produced the primary alcohol 20 that was then
2.2. Surface-acti6e properties
The critical micelle concentration (CMC), static
surface tension (the surface tension at CMC, kS),
and surfactant concentration in the solution phase
that will reduce the surface pressure of the solvent
by 20 mN/m (C20) were determined in water,
according to the procedures described in the ex-
perimental section. The dynamic behavior of the
compounds has been characterized by dynamic
surface tension measurements realized as previ-
ously described (Fainerman and Miller, 1994;
Miller et al., 1997). It is related to dynamic prop-
erties as wetting power, detergency power, emulsi-
fying power… Results are listed in Tables 1 and 2,
along with some additional data related to typical
or relevant detergents (Suga et al., 1968; Hato et
al., 1976; Dahanayake et al., 1986; Zhu et al.,
1991b).
3. Discussion
Preparation of the title compounds was easy
and they could be isolated on the multigram scale
in good yields. All the synthesized gemini com-
pounds were readily soluble in water. Their CMC
values were much smaller than that of the corre-
Scheme 5.

P. Renouf et al. / Chemistry and Physics of Lipids 99 (1999) 21–32
25
Scheme 6.
Table 1, compounds 25 and 26). That discrepancy
is not actually understood. The CMC value of the
heterodimeric gemini surfactant 5 is lower than
that of disodium disulfonate 4. That is to be
connected to the excellent micelle forming prop-
erty of surfactants containing a poly(ethylene ox-
ide) moiety (e.g. Igepal NP10) when compared to
sulfonates (SDS, 24).
Compounds 21 and 22 were prepared in order
to determine the true contribution of the spacer
group to the properties of the dimeric surfactants,
independently of the way it is connected to the
two constitutive monomers. However, the sodium
carboxylate 21 could not be tested as it is com-
pletely insoluble in water up to 60°C in the pH
range 7–11. The introduction of a methoxy group
on the alkyl chain in the sulfonate series decreases
the CMC value by an order of magnitude (com-
pare compound 22 with 24). Thus the sole intro-
duction of a ‘minor’ structural change near the
polar head of the monomeric surfactant can ac-
count for about half the micelle forming property
variations observed in geminis.
sponding monomeric surfactants (23, 24). The
disodium dicarboxylates (1 and 3) exhibit a CMC
value that is lower by roughly an order of magni-
tude lower than that of the corresponding dis-
odium disulfonates (2 and 4). Interestingly,
increasing the length of the connecting group
between the two lipophilic chains decreases the
CMC value in both carboxylate and sulfonate
series. That is definitely different from the results
obtained by Zhu et al. (1991b) revealing a higher
CMC for compounds with a longer spacer (see
Table 1
Surface active properties of the synthesized detergents and
some typical surfactants
Surfactant
CMC (mol/ kS (mN/m) C20 (mol/l) pC20
l)
1
2
3
4
1.3×10−5
9.3×10−5
0.8×10−5
4.8×10−5
1.5×10−5
26.4
31.4
38.7
35.5
39.8
2.4×10−6
10.8×10−6
1.8×10−6
7.4×10−6
2.3×10−6
5.4
8.6
4.4
6.5
6.5
5
21a
22
7.2×10−4
7.5×10−3
5.0×10−3
8.0×10−3
3.3×10−5
6.0×10−5
6.5×10−5
31.3
1.1×10−4
6.5
23b
24c
SDSd
25e
26e
Igepal
NP10
Table 2
38.9
37.6
28.0
36.0
31.3
2.0×10−3
4.4×10−3
8.0×10−6
10.1×10−6
2.4
2.2
4.1
5.9
Dynamic surface tension of the synthesized gemini surfactants
Surfactant
km (mN/m)
t* (s)
n
3.4×10−6 19.1
1
2
3
4
5
22
34.4
42.8
40.9
39.7
42.3
35.7
31.5
6.2
1.1
3.1
2.1
0.52
0.011
0.044
0.86
1.0
0.60
1.3
1.03
0.87
0.89
a The compound was completely insoluble below 60°C.
b At 55°C (Hato et al., 1976).
c At 40°C (Suga et al., 1968).
d At 25°C (Dahanayake et al., 1986).
e At 20°C (Zhu et al., 1991b).
Igepal NP10

26
P. Renouf et al. / Chemistry and Physics of Lipids 99 (1999) 21–32
Concerning the ability of gemini compounds to
values for t*, n and km were obtained using a
classical curve fitting software and are reported in
Table 2. In comparison with monomeric surfac-
tant Igepal NP10, the gemini compounds exhibit
very poor dynamic surface tension properties and
are slower by one to two orders of magnitude
(considering the t* values). This implies properties
related to dynamics (wetting, detergency…) to be
moderate for these compounds. Additionally,
compound 22 appears more powerful than Igepal
NP10 that can stand as a matter of reference for
surfactant dynamic properties.
lower surface tension (kS), as already observed by
others with compounds 25 and 26 (Zhu et al.,
1991b), the shortest connecting groups provide
the maximum efficiency (compare 1 to 3 and 2 to
4). In this respect, compound 1 definitely is the
most powerful of all the compounds in this work.
The tendency of the surfactants to adsorb at the
surface and consequently reduce the surface ten-
sion is quantified by the C20 value. Once again,
the gemini surfactants prove to be far more pow-
erful than conventional surfactants. Compounds
1-5 lower the surface tension of aqueous media by
20 mN/m in the micromolar range whereas
monomeric carboxylate and sulfonates act in the
millimolar range.
4. Experimental procedures
The CMC/C20 ratios (pC20) for each surfactant
were also reported (Table 1). The larger the pC20
the greater the tendency of the surfactant to ad-
sorb at the surface of aqueous media, relative to
its tendency to form micelles (Rosen, 1989). Con-
ventional monomeric surfactants generally exhibit
pC20 values less than 3. It has been proposed that
large pC20 values reflect the difficulty of packing
the hydrophobic chains in the micelle (due to the
high curvature of its surface) (Rosen, 1993). Com-
pounds 1-5 present pC20 values extending from
4.4 (compound 3) to 8.6 (compound 2), which is
extremely high. It is noteworthy that sodium sul-
fonate 22 has a high pC20 too, that can be clearly
related to the presence of the methoxy substituent
on the alkyl chain (compare with 24 or SDS).
The dynamic surface tension measurements for
the different compounds are displayed at Fig. 3.
The dynamic surface tension at time t, kt at a
constant surfactant concentration can be repre-
sented by the relaxation function described by
Rosen (Gao and Rosen, 1994; Hua and Rosen,
1988):
4.1. Materials
Unless otherwise stated, all chemicals used were
of commercial sources. THF, Et2O and dioxane
were distilled over Na/benzophenone and CH2Cl2
over CaH2, just before use. Methanol and ethanol
˚
were dried over 3 A molecular sieves previously
heated for 12 h at 180°C under reduced pressure
(0.1 mmHg). Reactions were monitored by TLC
(Merck precoated plates 0.25 mm, silica gel 60
F254, 0.040–0.060 mm, 230–400 mesh ASTM).
Liquid chromatography was performed on silica
gel 60 (Merck, 0.040–0.060 mm, 230–400 mesh
1
ASTM). H- and 13C-NMR spectra were recorded
on Brucker-WP-200-Sy and Brucker-Avance-
DPX-300 spectrometers, and chemical shifts l are
in ppm relative to an internal reference (1H:
CHCl3 at 7.27 ppm or CD2HOD at 3.31 ppm, the
latter for CDCl3/CD3OD solutions, 13C: CDCl3 at
77.0 ppm or CD3OD at 49.0 ppm, the latter for
CDCl3/CD3OD solutions). IR spectra were
recorded on a Perkin-Elmer-1600-FT spectrome-
ter, and absorption values are in cm−1
.
kt=km+(ko−km)/[1+(t/t*)n]
[2-(1-Carboxymethoxymethyl-undecyloxy)-dod-
ecyloxy]-acetic acid bis sodium salt (1). Dimethyl
ester 13 (1.52 g, 2.87 mmol) and sodium hydrox-
ide (0.23 g, 5.74 mmol) are refluxed in anhydrous
ethanol (15 ml) for 6 h. The solvent is removed in
where km is the mesoequilibrium surface tension
of the solution (where kt shows only a small
change with time), ko is the equilibrium surface
tension of the solvent (72.1 mN/m at 23°C for
water), t* is the time when the variation of kt is
maximum and n is a dimensionless constant. The
vacuo to yield
1
quantitatively (two dia-
stereomers, 1.56 g, 100%). 1H-NMR (CD3OD,
300 MHz) l 3.95–3.71 (m, 4H); 3.70–3.35 (m,

P. Renouf et al. / Chemistry and Physics of Lipids 99 (1999) 21–32
27
6H); 1.67–1.30 (m, 36H); 0.90 (t, J=6.8 Hz, 6H).
13C–NMR (CD3OD, 75 MHz) l 177.7; 177.4;
76.3; 75.1; 72.3; 71.8; 71.4; 33.0; 32.3; 30.9; 30.8;
30.7; 30.5; 30.1; 26.4; 23.7; 14.5. IR (film) w 3401;
2915; 2850; 1601; 1110.
3-{2-[1-(3-Sulfo-propoxymethyl)-undecyloxy]d-
odecyloxy}-propane-1-sulfonic acid bis sodium salt
(2). Sodium hydride (60% in oil, 0.41 g, 10.34
mmol) is added to a mixture of diol 9 (1.33 g, 3.44
mmol) and propane sultone (1.0 ml, 12.40 mmol)
in anhydrous dioxane (10 ml). The suspension is
refluxed for 24 h before methanol (20 ml) is added
at room temperature. The solvents are removed in
vacuo, water (150 ml) is added and the solution is
extracted with n-butanol (3×150 ml). The or-
ganic layer is dried over MgSO4 and evaporated
under reduced pressure. The crude solid obtained
is successively washed with n-hexane (50 ml) and
diethyl ether (50 ml) to yield analytically pure
compound 2 (two diastereomers, 2.13 g, 92%).
1H-NMR (CD3OD, 300 MHz) l 3.69–3.62 (m,
2H); 3.54 (t, J=11.8 Hz, 2H); 3.46–3.35 (m, 4H);
2.95–2.89 (m, 4H); 2.09–2.00 (m, 4H); 1.50–1.31
(m, 36H); 0.90 (t, J=6.8 Hz, 6H). 13C-NMR
(CD3OD, 75 MHz) l 77.2; 73.8; 69.6; 48.6; 32.5;
31.9; 29.8; 29.6 (b); 29.3; 25.3; 22.5; 13.3. IR (film)
w 2920; 2855; 1460; 1185; 1115; 1045.
[2-(2-{2-[2-(1-Carboxymethoxymethyl-undecy-
loxy)-ethoxy]-ethoxy}-ethoxy)-dodecyloxy]-acetic
acid bis sodium salt (3). Compound 3 (two dia-
Fig. 3. The dynamic surface tension measurements for the different compounds (see Section 4.2.2).

28
P. Renouf et al. / Chemistry and Physics of Lipids 99 (1999) 21–32
standing at −20°C and is collected by filtration
(12.8 g, 79%). 1H-NMR (CDCl3, 300 MHz) l
7.41–7.29 (m, SH); 4.58 (s, 2H); 3.86–3.81 (m,
1H); 3.54–3.50 (m, 1H); 3.37–3.31 (m, 1H); 1.46–
1.27 (m, 18H); 0.89 (t, J=6.0 Hz, 3H). 13C-NMR
(CDCl3, 75 MHz) l 138.2; 128.6; 127.9; 74.8; 73.5;
70.6; 33.3; 32.0; 29.9; 29.8; 29.7; 29.5; 25.6; 22.8;
14.3. IR (film) v 3450; 2925; 2855; 1100.
stereomers, 1.72 g, 99%) is obtained from
dimethyl ester 14 following the same procedure as
1
for 1. H-NMR (CD3OD, 300 MHz) l 3.87 (t,
J=6.8 Hz, 4H); 3.72–3.45 (m, 18H); 1.67–1.44
(m, 4H); 1.38–1.26 (m, 32H); 0.90 (t, J=6.8 Hz,
6H). 13C-NMR (CDCl3/CD3OD: 1/1, 50 MHz) l
176.8; 78.4 and 78.1; 71.3; 70.6; 69.5 and 69.3;
68.8; 66.3 and 65.9; 32.3; 30.5; 30.1; 29.7; 25.9;
23.0; 14.3. IR (film) w 3404; 2923; 2854; 1606;
1466; 1416; 1322; 1116.
2-(1-Benzyloxymethyl-undecyloxy)-dodecan-1-
ol (8). Sodium hydride (60% in oil, 1.70 g, 43.0
mmol) is slowly added to 1-benzyloxy-dodecan-2-
ol 6 (2.50 g, 8.6 mmol) in HMPA (2.5 ml) at 0°C.
The suspension is warmed to 60°C and a-bromod-
odecanoic acid (7.20 g, 28.0 mmol) in anhydrous
THF (20 ml) is added dropwise. The reaction
mixture is refluxed for 4 h before it is cooled
down to 0°C, acidified with aqueous HCl (10%),
and extracted with diethyl ether. The organic
layer is washed with brine, dried over MgSO4 and
reduced in vacuo to yield compound 7 (9.42 g)
that is used without further purification. Lithium
aluminium hydride (1.00 g, 26.3 mmol) is added
by portions at 0°C to the latter solid (9.00 g) in
anhydrous THF (100 ml). The mixture is stirred
at room temperature for 4 h, and then is refluxed
for 48 h. Excess reagent is decomposed at 0°C by
careful addition of water. The resulting solution is
acidified with aqueous HCl (10%), vigorously
stirred for 30 min, and extracted with diethyl
ether. The organic layer is washed with brine,
dried over MgSO4 and reduced in vacuo. The
crude residue is purified by chromatography on
silica gel (diethyl ether/hexane: 1/2 to 2/1) to give
compound 8 (two diastereomers, 2.43 g, 62%)
followed by a portion of the debenzylation
3-{2-[2-(2-{2-[1-(3-Sulfo-propoxymethyl)-unde-
cyloxy]-ethoxy}-ethoxy)-ethoxy]-dodecyloxy}-pr-
opane-1-sulfonic acid bis sodium salt (4). Com-
pound 4 (two diastereomers, 1.22 g, 81%) is ob-
tained from diol 12 following the same procedure
1
as for 2. H-NMR (CD3OD, 300 MHz) l 3.81–
3.48 (m, 22H); 2.99–2.91 (m, 4H); 2.12–1.98 (m,
4H); 1.48–1.28 (m, 36H); 0.90 (t, J=6.7 Hz, 6H).
13C-NMR (CD3OD, 75 MHz) l 80.3; 74.2; 71.8;
71.4; 70.8; 70.1; 49.3; 33.0; 32.7; 30.9; 30.8; 30.5;
26.5; 26.3; 23.7; 14.5. IR (film) w 2925; 2855; 1205;
1045.
3-[2-(2-{2-[1-methyl(PEG)oxymethyl-undecylo-
xy]-ethoxy}-ethexy)-dodecyloxy]-propane-1-sulfo-
nic acid sodium salt (5). Compound 5 (two
diastereomers, 1.12 g, 80%) is obtained from 18
1
following the same procedure as for 2. H-NMR
(CDCl3, 200 MHz) l 3.65–3.58 (m, 76H); 3.54–
3.49 (m, 6H); 3.42–3.38 (m, 2H); 2.92–2.84 (m,
2H); 2.07–1.99 (m, 2H); 1.43–1.21 (m, 36H); 0.83
(t, J=6.4 Hz, 6H). 13C-NMR (CDCl3, 50 MHz) l
79.0; 78.9 and 78.8; 73.3 and 73.2; 73.0; 71.7; 70.6;
70.5; 70.3; 70.2; 69.7; 68.7; 68.4; 68.2; 58.9; 48.2;
31.8; 31.4; 31.0 and 30.9; 29.7; 29.5; 29.2; 25.4 and
25.3; 25.2 and 25.0; 22.6; 14.0. IR (film) w 3502
(b); 2923; 2859; 1458; 1348; 1299; 1245; 1112;
1045.
1-Benzyloxy-dodecan-2-ol (6). Sodium hydride
(60% in oil, 2.90 g, 72.5 mmol) is added to
1,2-epoxydodecane (10.2 g, 55.4 mmol) in benzyl
alcohol (50 ml) at 0°C. The reaction mixture is
stirred at 80°C till complete consumption of the
epoxide. Diethyl ether is added at room tempera-
ture and the mixture is washed with aqueous
NH4Cl, brine, and dried over MgSO4. Ether and
most of benzyl alcohol are removed under re-
duced pressure. Compound 6 crystallizes on
1
product 9 (1.21 g, 38%). H-NMR (CDCl3, 300
MHz) l 7.38–7.26 (m, 5H); 4.62–4.52 (m, 2H);
3.83–3.40 (m, 6H); 1.52–1.24 (m, 36H); 0.87 (t,
J=6.8 Hz, 6H). 13C-NMR (CDCl3, 75 MHz) l
138.1 and 137.4; 128.4 and 128.2; 127.7 and 127.5;
80.6 and 78.8; 78.4 and 76.7; 77.6; 77.0; 73.4 and
73.1; 73.2 and 73.0; 65.6 and 64.1; 36.8; 32.3; 31.8;
31.6; 29.7; 29.5; 29.3; 25.7; 25.5; 25.2; 22.6; 14.0.
IR (film) w 2925; 2855; 1115.
2-(1-Hydroxymethyl-undecyloxy)-dodecan-1-ol
(9). Compound 8 (2.40 g, 5.0 mmol) and Pd/C
10% (0.1 g) in methanol are stirred overnight

P. Renouf et al. / Chemistry and Physics of Lipids 99 (1999) 21–32
29
1.55–1.22 (m, 36H); 0.90 (t, J=6.5 Hz, 6H).
13C-NMR (CDCl3, 75 MHz) l 81.4; 70.8 and
70.7; 70.2 and 70.1; 68.9 and 68.8; 64.5; 31.2; 31.1;
29.6; 29.5; 29.4 (b); 29.1; 25.5; 22.5; 13.9. IR (film)
w 3450; 2920; 2855; 1105.
under hydrogen atmosphere (1 atm). The catalyst
is removed by filtration over celite. The filtrate is
reduced in vacuo and the residue is purified by
chromatography on silica gel (hexane/ethyl ac-
etate: 4/1 to 2/1) to yield 9 as two separated
1
[2-(1-Methoxycarbonylmethoxymethyl-undecy-
loxy)-dodecyloxy]-acetic acid methyl ester (13).
Sodium hydride (60% in oil, 1.71 g, 41.4 mmol) is
slowly added to a solution of diol 9 (two
diastereomers, 2.00 g, 5.2 mmol) and HMPA (3
ml) in anhydrous THF (30 ml) at 0°C. A solution
of bromoacetic acid (2.92 g, 20.8 mmol) in THF
(10 ml) is added to the previous mixture which is
then refluxed for 24 h. Aqueous HCl (10%) is
added at 0°C and the resulting solution is ex-
tracted with ethyl acetate. The organic layer is
washed with brine, dried over MgSO4 and re-
duced in vacuo. The crude residue is stirred with
sulfuric acid (0.5 ml) in refluxing anhydrous
methanol (100 ml) for 16 h. Methanol is removed
in vacuo, ether (50 ml) is added and the solution
is washed with water and brine. The organic layer
is dried over MgSO4 and the residue is purified by
chromatography on silica gel (hexane/ethyl ac-
etate: 1/2) to yield the dimethyl ester compound
13 (two diastereomers, 0.88 g, 32%). 1H-NMR
(CDCl3, 300 MHz) l 4.12 (AB syst., JAB=16.6
Hz, Dw=6.2 Hz, 4H); 3.76 (s, 6H); 3.64–3.56 (m,
2H); 3.53–3.47 (m, 4H); 1.57–1.40 (m, 4H); 1.39–
1.19 (m, 32H); 0.89 (t, J=6.0 Hz, 6H). 13C-NMR
(CDCl3, 75 MHz) l 170.7; 77.4; 74.1; 68.5; 51.5;
32.3; 31.7; 29.7; 29.5 (b); 29.2; 25.4; 22.5; 14.0. IR
(film) w 2925; 2855; 1760; 1145.
diastereomers 9a and 9b (1.94 g, 99%). (9a) H-
NMR (CDCl3, 200 MHz) l 3.69–3.61 (m, 2H);
3.54–3.43 (m, 4H); 1.55–1.26 (m, 36H); 0.90 (t,
J=6.4 Hz, 6H). 13C-NMR (CDCl3, 50 MHz) l
78.1; 64.5; 31.9; 31.3; 29.8; 29.6 (b); 29.3; 25.5;
22.6; 14.1. IR (film) w 3317; 2917; 2851; 1467;
1
1086. (9b) H-NMR (CDCl3, 200 MHz) l 3.73–
3.65 (m, 2H); 3.55–3.43 (m, 4H); 1.55–1.27 (m,
36H); 0.90 (t, J=6.4 Hz, 6H). 13C-NMR (CDCl3,
50 MHz) l 80.4; 65.3; 32.4; 31.9; 29.8; 29.6 (b);
29.3; 25.6; 22.7; 14.1. IR (film) w 3336; 2925; 2857;
1460; 1069.
1-BenzylOxy-2-(2-{2-[2-(1-benzyloxylethyl-un-
decyloxy)-ethoxy]-ethoxy}-ethoxy)dodecane (11).
Sodium hydride (60% in oil, 1.2 g, 30.0 mmol) is
slowly added to a mixture of 1-benzyloxy-dode-
can-2-ol 6 (5.0 g, 17.0 mmol), triethyleneglycol
bismethanesulfonyl ester (3.1 g, 10.0 mmol),
HMPA (2 ml), and sodium iodide (30 ma, 0.2
mmol) in anhydrous THF (30 ml). The mixture is
stirred in refluxing THF for 16 h. Diethyl ether is
then added at room temperature and the resulting
solution is neutralized by careful addition of
aqueous HCl (10%). The organic layer is washed
with brine, dried over MgSO4 and reduced in
vacuo. The crude residue is purified by chro-
matography on silica gel (diethyl ether/hexane:
l/2) to yield 11 as a mixture of two diastereomers
(5.3 g, 89%). 1H-NMR (CDCl3, 300 MHz) l
7.37–7.23 (m, 10H); 4.55 (s, 4H); 3.78–3.72 (m,
2H); 3.68–3.60 (m, 10H); 3.51–3.42 (m, 6H);
1.51–1.42 (m, 4H); 1.40–1.21 (m, 32H); 0.89 (t,
J=6.5 Hz, 6H). 13C-NMR (CDCl3, 75 MHz) l
138.7; 129.7; 128.5; 127.8; 127.7; 79.5; 73.5; 72.9;
71.0; 70.7; 69.5; 32.1; 29.9; 29.8 (b); 29.5; 25.6;
22.8; 14.3. IR (film) w 2925; 2860; 1110.
[2-(2-{2-[2-(1-Methoxycarbonylmethoxymethyl-
undecyloxy)-ethoxy]-ethoxy}-ethoxy)dodecylaxy]-
acetic acid methyl ester (14). Compound 14 (two
diastereomers, 1.43 g, 70%) is obtained starting
from diol 12, and following the same procedure as
1
for 13. H-NMR (CDCl3, 300 MHz) l 4.15 (AB
syst., JAB=16.2 Hz, Dw=0.6 Hz, 4H); 3.78–3.73
(m, 8H); 3.69–3.45 (m, 16H); 1.74–1.26 (m, 36H);
0.88 (t, J=6.4 Hz, 6H). 13C-NMR (CDCl3, 75
MHz) l 170.5; 79.0; 73.7; 70.5; 70.2; 68.9; 68.3;
51.2; 31.5; 31.3; 29.4 (b); 29.3; 28.9; 25.0; 22.3;
13.7. IR (film) w 2925; 2860; 1755; 1140.
2-(2-{2-[2-(1-Hydroxyethyl-undecyloxy)-ethox-
y1-ethoxy}-ethoxy)-dodecan-1-ol (12). Compound
12 (two diastereomers, 3.1 g, 99%) is obtained
from 11 by catalytic hydrogenation, following the
1
same procedure as for 9. H-NMR (CDCl3, 300
1-Benzyloxy-2-{2-[2-(1-benzyloxymethyl-unde-
cyloxy)-ethoxy]-ethoxy}-dodecane (15). Com-
MHz) l 3.79–3.62 (m, 14H); 3.51–3.38 (m, 4H);

30
P. Renouf et al. / Chemistry and Physics of Lipids 99 (1999) 21–32
69.3; 58.9; 31.8; 29.7; 29.6; 29.3; 25.4; 22.6; 14.0.
IR (film) w 2920; 2855; 1115.
pound 15 (two diastereomers, 4.14 g, 74%) is
obtained starting from 6 and diethyleneglycol
bis-methane-sulfonyl ester, and following the
1-Hydroxy-2-(2-{2-[1-methyl(PEG)oxymethyl-
undecyloxy]-ethoxy}-ethoxy)-dodecane (18). Com-
pound 18 (two diastereomers, 2.47 g, 98%) is
obtained starting from 17, and following the
same procedure as described for 12. 1H-NMR
(CDCl3/CD3OD: 7/3, 300 MHz) l 3.82–3.25 (m,
82H); 3.30 (s, 3H); 1.50–1.18 (m, 36H); 0.89 (m,
6H). 13C-NMR (CDCl3, 75 MHz) 6 81.3; 79.0;
73.6; 71.6; 70.6; 70.2; 68.7; 64.3; 58.7; 31.7; 31.4;
30.9; 29.6; 29.4; 29.1; 25.4; 25.3; 22.4; 13.9. IR
(film) w 3420; 2920; 1110.
1-Benzyloxy-2-methoxy-dodecane (19). Hy-
droxy compound 6 (1.25 g, 4.3 mmol) in anhy-
drous THF (10 ml) is slowly added to sodium
hydride (60% in oil, 0.25 g, 6.2 mmol) previously
washed twice with anhydrous THF (3 ml).
Methyl iodide (0.75 ml, 12.0 mmol) is then
added and the resulting mixture is refluxed
overnight. The suspension is filtered and the
filtrate is reduced in vacuo. The residue is dis-
solved in diethyl ether, washed with aqueous
NH4Cl, water and brine. The organic layer is
dried over MgSO4 and concentrated to yield ana-
lytically pure compound 19 (1.20, 92%). 1H-
NMR (CDCl3, 300 MHz) l 7.37–7.29 (m, 5H);
4.58 (s, 2H); 3.50 (d, J=4.9 Hz, 2H); 3.43 (s,
3H); 3.35 (q, J=5.3 Hz, 1H); 1.54–1.25 (m,
18H); 0.91 (t, J=6.0 Hz, 3H). 13C-NMR
(CDCl3, 75 MHz) l 138.6; 128.5; 127.8; 127.7;
80.4; 73.5; 72.4; 57.7; 32.0; 31.6; 29.9; 29.8 (b);
29.5; 25.5; 22.8; 14.3. IR (film) w 2925; 2855;
1460; 1115.
1
same procedure as for 11. H-NMR (CDCl3, 300
MHz) l 7.35–7.25 (m, 10H); 4.55 (s, 4H); 3.79–
3.71 (m, 2H); 3.68–3.61 (m, 6H); 3.50–3.45 (m,
6H); 1.49–1.25 (m, 36H); 0.89 (t, J=6.5 Hz,
6H). 13C-NMR (CDCl3, 75 MHz) l 138.6; 128.4;
127.7; 79.5; 73.5; 72.9; 71.0; 69.5; 32.0; 29.9;
29.8; 29.5; 25.6; 22.8; 14.3. IR (film) 6 2925;
2855; 1115.
1-Benzyloxy-2-{2-[2-(1-hydroxymethyl-undecy-
loxy)-ethoxyI-ethoxy}-dodecane (16). Compound
16 (two diastereomers, 2.36 g, 70%) is obtained
starting from 15, using the same procedure as
described for 12, except that the reaction is con-
ducted in ethanol/hexane (85:15, v/v) during a
shorter period of time (4h). 1H-NMR (CDCl3,
300 MHz) l 7.36–7.27 (m, 5H); 4.55 (s, 2H);
3.82–3.42 (m, 14H); 1.47–1.26 (m, 36H); 0.89 (t,
J=6.5 Hz, 6H). 13C-NMR (CDCl3, 75 MHz) l
138.2; 128.0; 127.3; 127.2; 81.3; 79.1; 73.0; 72.5;
70.7; 70.6; 69.0; 64.5; 31.7; 31.2; 29.5; 29.4; 29.1;
25.4; 22.5; 13.8. IR (film) w 3470; 2925; 2860;
1105.
1-Benzyloxy-2-(2-{2-[1-methyl(PEG)oxymeth-
yl-undecyloxy1-ethoxy}-ethoxy)-dodecane
(17).
Sodium hydride (60% in oil, 0.50 g, 13.5 mmol)
is slowly added to compound 16 (1.27 g, 2.25
mmol) and polyethyleneglycol methyl ether
methane-sulfonyl ester (average MW: 830, 1.25 g,
1.5 mmol) in anhydrous dioxane (15 ml). The
reaction mixture is refluxed overnight before
methanol (2 ml) is added at room temperature.
The solvent is removed in vacuo, water is added
(100 ml) and the resulting solution is wished with
n-butanol (3×100 ml). The organic layers are
pulled together, dried over MgSO4 and evapo-
rated under reduced pressure. The residue is
purified by flash chromatography over a silica gel
pad (AcOEt/hexane: 1/1, then n-BuOH/CH2Cl2:
2-Methoxy-dodecan-1-ol (20). Compound 20
(1.13 g, 96%) is obtained starting from 19, and
1
following the same procedure as for 9. H-NMR
(CDCl3, 300 MHz) l 3.72–3.65 (m, 1H); 3.52–
3.45 (m, 1H); 3.41 (s, 3H); 3.30–3.23 (m, 1H);
1.56–1.24 (m, 18H); 0.89 (t, J=6.0 Hz, 3H).
13C-NMR (CDCl3, 75 MHz) l 81.8; 64.1; 57.2;
32.0; 30.4; 30.0; 29.7 (b); 29.5; 25.5; 22.8; 14.2.
IR (film) w 2930; 2855; 1460; 1100.
(2-Methoxy-dodecyloxy)-acetic acid sodium salt
(21). Sodium hydride (60% in oil, 0.76 g, 19.0
mmol) is slowly added to a solution of the hy-
droxy compound 20 (1.37 g, 6.3 mmol) and bro-
1
1/1) to yield 17 (1.95 g, 66%). H-NMR (CDCl3,
300 MHz) l 7.34–7.25m, 5H); 4.54 (s, 2H);
3.76–3.42 (m, 82H); 3.38 (s, 3H); 1.55–1.18 (m,
36H); 0.90 (t, J=6.5 Hz, 6H). 13C-NMR
(CDCl3, 75 MHz) l 138.4; 128.2; 127.5; 127.4;
79.3; 79.2; 73.9; 73.2; 72.7; 71.9; 70.8; 70.7; 70.5;

P. Renouf et al. / Chemistry and Physics of Lipids 99 (1999) 21–32
31
moacetic acid (1.39 g, 10.0 mmol) in anhydrous
THF (15 ml). The reaction mixture is refluxed
overnight and then decomposed by dropwise ad-
dition of methanol (1 ml). The solvent is removed
in vacuo and the residue is dissolved in n-butanol
and washed with water. The organic layer is dried
over MgSO4, concentrated, and the residue is
purified by chromatography on silica gel (ethyl
acetate/ethanol: 8/2, then chloroform/methanol/
water: 10/6/1) to yield (2-methoxy-dodecyloxy)-
acetic acid (1.10 g). The latter carboxylic acid is
treated with aqueous sodium hydroxide (10%)
and the resulting mixture is extracted with n-bu-
tanol. The organic layer is dried over MgSO4 and
concentrated to yield the sodium salt 21 (1.25 g,
stirrup in case of wetting problem of the plate.
The plate or the stirrup were connected to an
electrobalance (Tensimat n°3, Prolabo). Air-water
interfaces were swept clean by suction and let rest
for 20 minutes at 23°C prior to experiments.
Measurements were repeated until no significant
change in the surface pressure value was recorded.
Critical micelle concentrations were determined
using a series of aqueous solutions at various
concentrations. The CMC was determined from
the break point of each surface versus concentra-
tion (on log scale) curve.
4.2.2. Dynamic surface tension measurements
The dynamic surface tensions were determined
with a LAUDA MPT1 surface tensiometer using
the maximum bubble pressure method (Fainer-
man and Miller, 1994; Miller et al., 1997).The
apparatus was fit out with a 77 mm capillary tube
and the bubble life times were in the range 0.003–
30 s. Unless otherwise stated, all experiments were
realized at 1 g/l surfactant concentration, at 23°C.
The bubbles were blown with surrounding air
(pump included in the apparatus). The LAUDA
instrument was interfaced to a computer and all
data were analyzed with a software supplied by
LAUDA.
1
67%). H-NMR (CD3OD, 300 MHz) l 3.96 (s,
2H); 3.63–3.51 (m, 2H); 3.40 (s, 3H); 3.43–3.37
(m, 1H); 1.54–1.30 (m, 18H); 0.90 (t, J=6.8 Hz,
3H). 13C-NMR (CD3OD/CDCl3: 1/1, 75 MHz) l
173.6; 79.3; 72.3; 70.5; 56.5; 31.2; 29.3; 29.0 (b);
28.7; 24.7; 22.0; 13.7. IR (film) 6 3421; 2517; 1637;
1464; 1116.
3-(2-Methoxy-dodecyloxy)-propan-l-sulfonic
acid sodium salt (22). Compound 22 (1.66 g, 87%)
is obtained starting from 20, and following the
same procedure as for 2. 1H-NMR (CD3OD/
CDCl3: 2/8, 200 MHz) l 3.55 (t, J=6.4 Hz, 2H);
3.46–3.41 (m, 1H); 3.38 (s, 3H); 3.32–3.29 (m,
2H); 2.96–2.88 (m, 2H); 2.08–2.01 (m, 2H); 1.55–
1.20 (m, 18H); 0.87 (t, J=7.1 Hz, 3H). 13C-NMR
(CD3OD, 75 MHz) l 80.3; 72.5; 69.6; 56.6; 48.4;
31.8; 31.2; 29.7; 29.5 (b); 29.3; 25.3; 25.2; 22.5;
13.3. IR (film) 6 3427; 2924; 2854; 2533; 1187.
Acknowledgements
The authors are thankful to Gilles Gue´rin
(Rhoˆne-Poulenc, Centre de Recherche d’Aubervil-
liers) for fruitful discussion.
4.2. Methods
Igepal NP10 ((nonylphenoxy)polyethoxyetha-
nol, nonylphenol 10 EO) was from Rhoˆne-Pou-
lenc and was used without further purification.
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