A facile route towards the preparation of ultra-long-Chain amidosulfobetaine surfactants

Article abstract of DOI:10.1055/s-0029-1217973

A series of novel, ultra-long-chain amidosulfobetaine surfactants were prepared by amidation of ultra-long-chain fatty acids directly with N,N-dimethyl-1,3-propanediamine in the absence of solvents, followed by quaternization of the intermediates with 1,3-propanesultone in ethyl acetate.

Full text of DOI:10.1055/s-0029-1217973

LETTER
2655
A Facile Route towards the Preparation of Ultra-Long-Chain
Amidosulfobetaine Surfactants
U
ltra-Long-Cha
o
in
A
midosul
n
fobetaine Su
g
rfactants lin Chu,a,b Yujun Feng*a
a
Chengdu Institute of Organic Chemistry, Chinese Academy of Sciences, Chengdu 610041, P. R. of China
Graduate School of Chinese Academy of Sciences, Beijing 100049, P. R. of China
Fax +86(28)85236874; E-mail: yjfeng@cioc.ac.cn
b
Received 2 June 2009
chain sulfobetaines could form worm-like micelles, it is
expected that the self-assembly aggregates would exhibit
more interesting behaviors in the presence of inorganic
species such as acid, base and salt.
Abstract: A series of novel, ultra-long-chain amidosulfobetaine
surfactants were prepared by amidation of ultra-long-chain fatty ac-
ids directly with N,N-dimethyl-1,3-propanediamine in the absence
of solvents, followed by quaternization of the intermediates with
1,3-propanesultone in ethyl acetate.
Because of their poor water solubility, the length of hy-
drophobic chains in sulfobetaine surfactants are still lim-
ited to a maximum of 18 carbon atoms,11 and the general
synthetic strategy is quaternization of the common start-
ing material N-alkyl-N,N-dimethylamine with either sodi-
um 2-bromo-1-ethanesulfonate, sodium 3-chloro-2-
hydroxy-propanesulfonate, or a large excess of a,w-dibro-
mide, to form a bromoalkyl quaternary bromide salt, fol-
lowed by sulfonation with aqueous bisulfite.11a
Disadvantages of this approach, such as the formation of
by-products and low yields have been noted for these pro-
cedures, and the lack of commercially available ultra-
long-chain dimethyl amines further impedes the prepara-
tion of the corresponding sulfobetaine surfactants.
Key words: ultra-long-chain surfactants, amidosulfobetaine sur-
factants, worm-like micelles, self-assembly aggregates, facile syn-
thesis
Surfactants are amphiphilic compounds known to have
both hydrophobic and hydrophilic groups in the same
molecule. They are widely used not only as detergents in
daily applications,1 but also as templates for constructing
mesoporous materials2 or nanoparticles,3 carrier vehicles
for drug delivery,4 micellar catalysts in organic synthesis,5
and even as models used to develop fundamental
understanding6 of self-assembly mechanisms due to their
polymorphism ordered topologies in aqueous solution.7
To the best of our knowledge, however, the number of
carbon atoms in the non-polar tails for most surfactants
that have appeared to date are normally between 8 and 16
in order to ensure good water-solubility.1
Recently, ultra-long-chain surfactants8 with hydrophobic
tails longer than C18 have gained increasing interest due to
their potential to self-assemble into worm-like micelles
which show peculiar macroscopic viscoelastic rheological
responses.8d,f,9 Among long-chain amphiphilic molecules,
the most frequently investigated are two cationic surfac-
tants, erucyl bis-(hydroxyethyl)methylammonium chlo-
ride (EHAC) and erucyl trimethylammonium chloride
(ETAC),8d while their long-chain zwitterionic counter-
parts are less well documented. Studies that have been re-
ported so far involve only the carboxylic zwitterionic
surfactants erucyl dimethyl amidopropyl carboxylic be-
taine (EDAB)8f and 6-(eicosyldimethyl-ammonio) hex-
anoate (C20AH);8c the corresponding sulfobetaine
surfactants are seldom found. However, compared with
carboxylic betaines, sulfobetaines are more stable over the
entire pH range, and they exhibit better tolerance to elec-
trolytes, higher detergency, stronger lime soap dispers-
ibility and cause less skin irritation.10 If the ultra-long-
Alternatively, we report herein a facile route to the prepa-
ration of a series of amidosulfobetaine surfactants from
the commercially available ultra-long-chain natural fatty
acids. The general synthetic procedure is outlined in
Scheme 1. Tertiary ammine intermediates were prepared
by amidation of ultra-long-chain fatty acids directly with
N,N-dimethyl-1,3-propanediamine, without solvent, at
160–165 °C. The resulting products were quaternized by
O
O
NaF/Al2O3
Me
Me
R
OH
O
+
H2N
N
R
N
N
H
Me
Me
CnAMPM or UCnAMPM
O
S
O
O
–
R
N
N
SO3
EtOAc
Me
Me
H
CnAMP3SB or UCnAMP3SB
for CnAMP3SB, n = 18, 22, 24, 28, RCOOH = Me(CH2)n–2COOH
for UC18AMP3SB,
O
RCOOH =
OH
for UC22AMP3SB,
RCOOH =
O
OH
SYNLETT 2009, No. 16, pp 2655–2658
x
x
.x
x
.2
0
0
9
Advanced online publication: 09.09.2009
DOI: 10.1055/s-0029-1217973; Art ID: W08109ST
© Georg Thieme Verlag Stuttgart · New York
Scheme 1 Synthetic pathway for the series of ultra-long-chain
amidosulfobetaine surfactants

2656
Z. Chu, Y. Feng
LETTER
1,3-propanesultone at around 80–85 °C in ethyl acetate to such as bleaching earth, silica gel, zeolite, pumice, phos-
obtain a series of ultra-long-chain amidosulfobetaines phoric acid, sulfuric acid, boric acid, and their acid
(Table 1).
salts,16a but very long reaction times (48–65 h) were re-
quired using these inefficient catalysts.16a Though alkyl ti-
tanium or alkyl tin catalysts16b were also found to be able
to catalyze such a reaction, the preparation of these cata-
lysts was rather complex. Fluoride ion was demonstrated
to be an effective catalysis17 and its catalytic activity was
ascribed to the enhanced basicity of the fluoride ion by the
catalytic system.17d Particularly, since KF was shown to
be an effective catalyst for esterification reactions,17d it
was expected to also catalyze the amidation reaction un-
der investigation in this work. However, since less inex-
pensive NaF was also found to be effective in
amidation,17e we chose to use this catalyst in the first step
of the reaction. Under these conditions, high yields of the
intermediate amides were finally obtained (Table 1).
The key step in this synthetic protocol is the preparation
of the alkyl-amido tertiary amine intermediates
(Scheme 1). Historically, the synthesis of amides have
been based mostly on either activated acid derivatives (ac-
id chlorides and anhydrides) or rearrangement reactions
induced by an acid or base, however, both approaches of-
ten produce toxic chemical wastes and involve tedious
procedures.12 Preparation of amides under neutral condi-
tions and without the generation of waste is a challenging
goal.13 A large amount of benzene was used as solvent in
the preparation of stearoylamidopropyl dimethyl amine in
an earlier work.14 Similarly, a methyl N-alkylsuccinamate
intermediate was prepared later by reacting a primary fat-
ty amine with b-carbomethoxypropionyl chloride in anhy-
drous diethyl ether using pyridine as solvent.15 However, The physical similarity of the starting fatty acids, interme-
not only did this process produce pyridine hydrochloride diates, and final amidosulfobetaines, as well as their poor
as a by-product, but also the yield was just 79%. Here, we solubility in most of the solvents, renders traditional re-
describe a direct reaction of ultra-long-chain fatty acids crystallization or column chromatography unable to iso-
with DMPDA, which avoids the use of any solvents, and late the final products from the residues. This becomes
gives extremely high yields and good purity of intermedi- even more difficult when dealing with the amidosulfobe-
ates (Table 1).
taine bearing a hydrophobic length C28. The amphiphilic
characteristic of these compounds also results in foaming,
emulsification and agglutination, which further hinders
the purification process. We found that some solvents
were suitable to wash out the residues from the products
during the purification process, and high-purity ultra-
long-chain amidosulfobetaines products could be ob-
tained.18 As depicted in Table 1, the purity of all the com-
In order to accelerate the production of alkyl amidopropyl
tertiary amine intermediate, NaF was used as catalyst and
4 Å molecular sieves (or Al2O3) was adopted to replace
traditional solvents (e.g. benzene or xylene), to immedi-
ately remove the by-product water produced. The amida-
tion reaction could be catalyzed16 by traditional catalysts
Table 1 Purity and Yield of Ultra-Long-Chain Intermediate Tertiary Amines and Final Amidosulfobetaine Surfactants
Product
Reaction temperature (°C) Reaction time (h) Solventa
Purity (%)b
99.69
99.86
99.70
96.08
99.90
99.92
99.35
99.32
97.06
99.69
99.60
Yield (%)c
C18AMPM
160
165
165
165
160
80
10
11
12
12
10
8
cold acetoned
71
92
95
96
82
91
84
93
95
84
58
C22AMPM
acetonee
C24AMPM
acetonee
C28AMPM
acetonee
UC22AMPM
C18AMP3SB
C22AMP3SB
C24AMP3SB
C28AMP3SB
UC22AMP3SB
UC18AMP3SB
cold acetoned
EtOAc, Et2Oe
EtOAc, Et2Oe
EtOAce, acetone–i-PrOHf
EtOAce, acetone–i-PrOHg
EtOAc, Et2Oe
acetone–i-PrOHh
80
10
12
12
12
10
85
85
80
80
a Solvent used in the purification process.
b Determined by HPLC.
c Yield of isolated pure product.
d Performed at about 5–10 °C.
e Performed at r.t.
f Performed at about 40 °C.
g Performed at about 50 °C.
h Intermediate not isolated, but product purified by successive recrystallization from the mixture of acetone and i-PrOH.
Synlett 2009, No. 16, 2655–2658 © Thieme Stuttgart · New York

LETTER
Ultra-Long-Chain Amidosulfobetaine Surfactants
2657
Ziserman, L.; Danino, D.; Raghavan, S. R. Langmuir 2007,
23, 12849.
(9) Dreiss, C. A. Soft Matter 2007, 3, 956.
pounds exceeded 96%, and the yields were above 81%
except for that of C18AMPM and UC18AMP3SB.19 The
lower yield for these two compounds resulted from their
partial solubility in the solvent due to their shorter hydro-
phobic chains. For this reason, the UC18AMPM interme-
diate was not isolated, and the corresponding final product
3-(N-oleamidopropyl-N,N-dimethylammonium)propane-
sulfonate (UC18AMP3SB) was purified by successive re-
crystallizations from the mixture of acetone and i-PrOH
(acetone/i-PrOH = 3:1, v/v).
(10) (a) In Amphoteric Surfactants, 2nd ed.; Lomax, E. G., Ed.;
Marcel Dekker: New York, 1996, 75. (b) Rosen, M. J.
Surfactants and Interfacial Phenomenon, 3rd ed.; John
Wiley & Sons: New York, 2004, 28.
(11) (a) Parris, N.; Weil, J. K.; Linfield, W. M. J. Am. Oil Chem.
Soc. 1976, 53, 97. (b) Rabilloud, T.; Gianazza, E.; Cattò, N.;
Righetti, P. G. Anal. Biochem. 1990, 185, 94. (c) Brunel, S.;
Chevalier, Y.; Le Perchec, P. Tetrahedron 1989, 45, 3363.
(12) Smith, M. B. Compendium of Organic Synthetic Methods,
Vol. 9; Wiley: New York, 2001, 100.
(13) Gunanathan, C.; Ben-David, Y.; Milstein, D. Science 2007,
317, 790.
(14) Ernst, R. US 3280179, 1966.
(15) Micich, T. J.; Linfeld, W. M.; Weil, J. K. J. Am. Oil Chem.
Soc. 1977, 54, 91.
(16) (a) Werdehausen, A.; Weiss, H.; Schutt, H. US 3816483,
1974. (b) Li, T. Z.; Lamont, J. US 4277410, 1981.
(17) (a) Holz, S.; Albeck, M.; Roppoport, Z. Synthesis 1975,
162. (b) Kuwajima, I.; Murofushi, T.; Nakamura, E.
Synthesis 1976, 602. (c) Clark, J. H.; Miller, J. M.
Tetrahedron Lett. 1977, 18, 599. (d) Yanagida, S.;
Takahashi, K.; Okahara, M. J. Org. Chem. 1979, 44, 1099.
(e) Chen, Ch.; Wu, Q.; He, L. J. Beijing Inst. Petro-Chem.
Tech. 2002, 10(3), 40.
In summary, a series of novel, ultra-long-chain amidosul-
fobetaine surfactants were synthesized in high yield and
high purity via an efficient and facile process from com-
mercially available fatty acids. The protocol will be par-
ticularly useful in the synthesis of ultra-long-chain
surfactants. The final ultra-long-chain amphoteric surfac-
tants exhibit excellent surface-active properties and can
form worm-like micelles at extremely low concentrations.
Besides, their potential in forming soft matters with or-
dered structures, possible applications in tertiary oil re-
covery with their viscoelastic and unique surface-active
characteristics are expected. Further studies on their inter-
facial properties and rheological behaviors are currently
underway.
(18) Preparation of 3-(N-behenamidopropyl-N,N-dimethyl-
ammonium) propanesulfonate (C22AMP3SB); Typical
Procedure: Behenic acid (200 mmol, 68.12 g), N,N-
dimethyl-1,3-propanediamine (DMPDA; 300 mmol, 30.65
g), and NaF (0.30 g) were introduced into a three-necked
flask. The reaction mixture was refluxed at 165 °C under N2
atmosphere for 6 h, during which the by-product H2O was
absorbed continuously by Al2O3 placed in the solvent still
head. Afterwards, further DMPDA (100 mmol, 10.22 g) was
added and the reaction was continued for another 5 h. The
excess of DMPDA was removed and the residues were
washed with acetone [4 × 200 mL containing H2O (10 mL)
to remove NaF]. The purified product was dried under
vacuum at 40 °C for 24 h to give N-behenamidopropyl-N,N-
dimethylamine (C22AMPM) with a purity 99.86% (HPLC)
and a yield of 92.41% (78.50 g). 1H NMR (300 MHz,
CD3OD): d = 0.90 (t, J = 6.66 Hz, 3H), 1.29 (m, 36H), 1.59–
1.70 (m, 4H), 2.17 (t, J = 7.42 Hz, 2H), 2.25 (s, 6H), 2.35 (m,
2H), 3.19 (t, J = 6.94 Hz, 2H); 13C NMR (75 MHz, CD3OD):
d = 14.42, 23.72, 27.05, 28.20, 30.29–30.74, 33.06, 37.17,
38.57, 45.42, 58.21, 176.26; HRMS (ESI): m/z [M + H]+
calcd for C27H57N2O: 425.4465; found: 425.4444; Anal.
Calcd for C27H56N2O: C, 76.35; H, 13.29; N, 6.60. Found: C,
76.13; H, 13.26; N, 6.45. In the next step, C22AMPM (20
mmol, 8.50 g), 1,3-propanesultone (30 mmol, 3.66 g), and
EtOAc (100 mL) were introduced to a round-bottom flask.
After 10 h of reflux (~80 °C), the white precipitate was
filtered from the solution and washed with EtOAc (3 × 200
mL) and Et2O (3 × 200 mL) successively. The product was
dried under vacuum at 40 °C for 24 h, to give the final
product C22AMP3SB with purity 99.35% (HPLC) and a
yield of 84.52% (9.24 g). Detailed preparation procedures
and structural characterizations of other amidosulfobetaines
are available in the supporting information. 1H NMR (300
MHz, CD3OD): d = 0.90 (t, J = 6.66 Hz, 3H), 1.29 (m, 36H),
1.60 (m, 2H), 1.98 (m, 2H), 2.18–2.23 (m, 4H), 2.87 (t,
J = 6.65 Hz, 2H), 3.10 (s, 6H), 3.25–3.36 (m, 4H), 3.53 (m,
2H); 13C NMR (75 MHz, CD3OD): d = 14.39, 19.86, 23.70,
23.99, 26.90, 30.99–30.73, 33.05, 37.13, 48.71, 51.56,
63.26, 63.81 176.56; HRMS (ESI): m/z [M + Na]+ calcd for
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synlett.
Acknowledgment
Financial support from the Chinese Academy of Sciences for this
work is greatly acknowledged.
References and Notes
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Applied Surfactants: Principles and Applications; Wiley-
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(2) Lin, H.-P.; Mou, Ch.-Y. Acc. Chem. Res. 2002, 35, 927.
(3) (a) Ji, Q.; Acharya, S.; Hill, J. P.; Richards, G. J.; Ariga, K.
Adv. Mater. 2008, 20, 4027. (b) Zemb, T. h.; Budois, M.;
Demé, B.; Gulik-Krzywicki, Th. Science 1999, 283, 816.
(4) Soussan, E.; Cassel, S.; Blanzat, M.; Rico-Lattes, I. Angew.
Chem. Int. Ed. 2009, 48, 274.
(5) Dwars, T.; Paetzold, E.; Oehme, G. Angew. Chem. Int. Ed.
2005, 44, 7174.
(6) (a) Manne, S.; Gaub, H. E. Science 1995, 270, 1480.
(b) Hoffmann, H. Adv. Mater. 1994, 6, 116. (c) Menger, F.
M. Proc. Natl. Acad. Sci. U.S.A. 2002, 99, 4818. (d)Safran,
S. A.; Pincus, P.; Andelman, D. Science 1990, 248, 354.
(7) In Dynamics of Surfactant Self-Assemblies: Micelles,
Microemulsions, Vesicles, and Lyotropic Phases, Surfactant
Series, Vol. 125; Zana, R., Ed.; CRC Press: Boca Raton,
2005, 11.
(8) (a) McGrady, J.; Laughlin, R. G. Synthesis 1984, 426.
(b) Brode, P. F. III. Langmuir 1988, 4, 176. (c) Hodge, D.
J.; Laughin, R. G.; Ottewill, R. H.; Renniell, A. R. Langmuir
1991, 7, 878. (d) Raghavan, S. R.; Kaler, E. W. Langmuir
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H. J. Oleo Sci. 2004, 53, 35. (f) Kumar, R.; Kalur, G. C.;
Synlett 2009, No. 16, 2655–2658 © Thieme Stuttgart · New York

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Z. Chu, Y. Feng
LETTER
C30H62N2NaO4S: 569.4323; found: 569.4318; Anal. Calcd
for C30H62N2O4S·0.7H2O: C, 64.40; H, 11.42; N, 5.01; S,
5.73. Found: C, 64.51; H, 11.35; N, 5.06; S, 5.47.
2H); 13C NMR (75 MHz, CD3OD): d = 14.47, 19.88, 23.72,
23.92, 26.91, 28.12, 28.14, 30.24–30.84, 33.04, 37.09,
37.14, 48.56, 51.48, 63.21, 63.80, 130.77, 130.87, 176.59;
HRMS (ESI): m/z [M + Na]+ calcd for C26H52N2NaO4S:
511.3540; found: 511.3531; Anal. Calcd for
(19) Data for UC18AMP3SB: 1H NMR (300 MHz, CD3OD): d =
0.93 (t, J = 6.70 Hz, 3H), 1.32–1.36 (m, 20H), 1.58 (m, 2H),
2.02–2.06 (m, 6H), 2.21–2.26 (m, 4H), 2.90 (t, J = 6.72 Hz,
2H), 3.13 (s, 6H), 3.28–3.39 (m, 4H), 3.56 (m, 2H), 5.37 (m,
C26H52N2O4S·1.2H2O: C, 61.18; H, 10.74; N, 5.49; S, 6.28.
Found: C, 61.28; H, 10.73; N, 5.45; S, 6.27.
Synlett 2009, No. 16, 2655–2658 © Thieme Stuttgart · New York