A synthetic route to sulfobetaine methacrylates with varying charge distance

Article abstract of DOI:10.1002/ejoc.201402734

A general synthetic strategy is described that enables access to a library of new sulfobetaine methacrylates starting from commercially available precursors. The three-step procedure allows the distance between the quaternary amine and the sulfonate group (inner charge distance) to be varied by selecting the corresponding dibromoalkane in the first step. A key step is the final esterification, in which methacrylic acid acts as solvent as well as reagent for the zwitterionic hydroxy intermediates. Thus, it is possible to synthesize monomeric precursors with up to twelve methylene groups between the positive and the negative charge. A selection of these monomers has been successfully tested for their ability to polymerize using free-radical polymerization.

Full text of DOI:10.1002/ejoc.201402734

Job/Unit: O42734
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Date: 03-11-14 15:03:01
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FULL PAPER
DOI: 10.1002/ejoc.201402734
A Synthetic Route to Sulfobetaine Methacrylates with Varying Charge
Distance
Domenic Kratzer,[a] Leonie Barner,[a,b] Christian Friedmann,[a] Stefan Bräse,[b,c] and
Joerg Lahann*[a,b]
Keywords: Synthetic methods / Materials science / Surfactants / Zwitterions / Polymerization
A general synthetic strategy is described that enables access
to a library of new sulfobetaine methacrylates starting from
commercially available precursors. The three-step procedure
allows the distance between the quaternary amine and the
acts as solvent as well as reagent for the zwitterionic hydroxy
intermediates. Thus, it is possible to synthesize monomeric
precursors with up to twelve methylene groups between the
positive and the negative charge. A selection of these mono-
sulfonate group (inner charge distance) to be varied by se- mers has been successfully tested for their ability to polymer-
lecting the corresponding dibromoalkane in the first step. A
key step is the final esterification, in which methacrylic acid
ize using free-radical polymerization.
tegies for the preparation of new zwitterionic precursors is
of great interest. In principle, sulfobetaine monomers are
easily accessible through ring-opening reaction of sultones
by using tertiary amines bearing polymerizable groups as
nucleophiles (Scheme 1).[9] Laschewsky et al. used this gene-
ral procedure to synthesize a library of sulfobetaine precur-
sors, in which the structure of the monomer was varied by
selecting a suitable nucleophile.[10] The corresponding poly-
mers obtained by free-radical polymerization of these
monomers were furthermore classified by their polymer ge-
ometry. Although this general synthetic procedure leads to
a large number of different molecules, the method is limited
to monomers bearing three or four methylene groups be-
tween the positive and the negative charge (inner charge
distance).
Introduction
Zwitterionic (macro)molecules are known for their wide
spectrum of interesting properties and they are used in
many different fields of applied chemistry and materials sci-
ence.[1] Applications range from polar surfactants[2] and sta-
tionary phases in zwitterionic hydrophilic interaction
chromatography[3] to their use as polymer brushes for sur-
face modifications.[4] When attached to surfaces, zwitter-
ionic polymers are utilized as antifouling materials to pre-
vent nonspecific adsorption of proteins[5] or the adhesion of
bacteria.[6] In particular, poly(sulfobetaine) coated surfaces
have recently attracted attention as potential cell culture
substrates because of their ability to sustain long-term
growth of human embryonic stem cells.[7] Furthermore, the
long-term stability of cell micropatterns on poly(sulfo-
betaine)-patterned surfaces was reported.[8]
Most of the applications mentioned above require zwit-
terionic monomers bearing polymerizable vinyl groups such
as methacrylate or acrylate derivatives. Because the struc-
ture of the monomeric unit influences the properties of the
corresponding polymer, the development of synthetic stra-
Scheme 1. General synthetic route to sulfobetaine monomers via
sultones; R1 = H, CH3. X = O, NH. k = 2–11.
[a] Institut für Funktionelle Grenzflächen (IFG), Karlsruhe
Institute of Technology (KIT),
Weers et al. investigated the influence of the inner charge
distance on the solution properties of carboxy- and sulfo-
betaines. For this purpose, sulfobetaines with inner charge
distances as high as six methylene groups were synthesized
through the reaction of tertiary alkylamines with a large
excess of dibromoalkanes and subsequent sulfonation of the
remaining bromine.[11] Although this procedure does not in-
clude the introduction of polymerizable vinylic groups, in
principle, it enables access to a group of sulfobetaines with
varying charge separation distance.
Hermann-von-Helmholtz-Platz 1,
76344 Eggenstein-Leopoldshafen, Germany
E-mail: joerg.lahann@kit.edu
http://www.ifg.kit.edu/85php
[b] Soft Matter Synthesis Laboratory, Institut für Biologische
Grenzflächen, Karlsruhe Institute of Technology (KIT),
Hermann-von-Helmholtz-Platz 1,
76344 Eggenstein-Leopoldshafen, Germany
[c] Institut für Organische Chemie, Karlsruhe Institute of
Technology (KIT),
Fritz-Haber-Weg 6, 76131 Karlsruhe, Germany
Supporting information for this article is available on the
WWW under http://dx.doi.org/10.1002/ejoc.201402734.
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D. Kratzer, L. Barner, C. Friedmann, S. Bräse, J. Lahann
FULL PAPER
Currently, there are only a few published procedures that
allow access to polymerizable sulfobetaine monomers with
Results and Discussion
inner charge distances of less than three or more than four Monomer Synthesis
methylene groups. Terayama et al. published a procedure
Starting from commercially available 1,n-dibromoalk-
for the synthesis of a sulfobetaine methacrylate with only
two methylene groups between the charge-bearing groups,
through the reaction of 2-(dimethylamino)ethyl methacryl-
ate with vinylsulfonyl chloride.[12] However, this specialized
route is limited to only this specific inner charge distance.
Sonnenschein et al. reported the synthesis of a group of
styrene sulfobetaine monomers with inner charge distances
ranging from one to five methylene groups, aiming to inves-
tigate the effects of the charge distances on zwitterionic ion
chromatography separations. The presented sulfonates were
synthesized by applying a series of nucleophilic substitution
reactions (including the ring-opening reaction of sultones),
whereby the synthesis protocols were chosen according to
their efficacy depending on the number of methylene groups
between the charges.[13] However, the described method for
the monomer bearing five methylene groups through con-
version of 5-bromopentane-1-sulfonate with a tertiary
amine can, in theory, be adapted to the synthesis of sulfo-
betaines bearing more than five methylene groups between
the charges.
anes 2c–g, the bromoalkyl quaternary bromide salts 3c–g
were accessible through nucleophilic substitution by using
2-(dimethylamino)ethanol (1) as nucleophile (Table 1).
Table 1. Formation of the bromoalkyl quaternary bromide salts
(Step 1).
Entry Starting material
n
Product Yield [%]
1
2
3
4
5
1,4-dibromobutane (2c)
4
5
6
8
12
3c
3d
3e
3f
62
76
75
80
84
1,5-dibromopentane (2d)
1,6-dibromohexane (2e)
1,8-dibromooctane (2f)
1,12-dibromododecane (2g)
3g
To minimize the formation of the double-substituted side
Our work has been motivated by the need to develop a product, an excess of the dibromoalkane (fourfold) and the
generic and efficient synthesis protocol with which to access slow addition of the nucleophile over a period of 6 h was
sulfobetaine methacrylates with free control over the necessary. Given their insolubility in acetone, the small
number of methylene groups between the charges. We pres- amounts of double-substituted side product could easily be
ent a three-step synthesis for sulfobetaine methacrylates removed by filtration. The main products 3c–g, on the other
with variably controllable inner charge distances starting hand, were soluble in all cases. After the reaction, the sol-
from commercially available, inexpensive precursors vent was removed and a mixture of ethyl acetate and water
(Scheme 2). The number of methylene groups between the (50:50) was added. The target compounds could be isolated
two charges in the final monomer is determined by the from the aqueous phase and were used for the next step
choice of the corresponding 1,n-dibromoalkane, under without further purification. The excess dibromoalkanes
otherwise identical conditions, underpinning the highly ge- were recovered from the organic phase, thus making the
neral character of this procedure. Thus, our approach will first step highly efficient. The choice of acetone as the sol-
enable broad access to a library of new zwitterionic mono- vent was critically important because the direct use of ethyl
mers, which represent useful building blocks for applica- acetate as solvent led, in case of 3e, to the formation of the
tions in different fields of biology, polymer chemistry, and double-substituted compound as the main product.
materials science.
The second step of the procedure included the conversion
of the bromoalkyl quaternary bromide salts 3c–g with
sodium sulfite, leading to the corresponding sulfobetaine
hydroxy intermediates 4c–g (Table 2). To demonstrate the
universality of our approach, we decided to expand the re-
action sequence to include the synthesis of sulfobetaine
methacrylates having two to twelve methylene groups (n =
2–12) between the amine and the sulfonate group. Although
several of these monomers have not previously been re-
ported, alternative, but less universal synthetic strategies ex-
ist for compounds 5a–c (n = 2–4).[10,12a] Where possible,
our analytical results were compared to the corresponding
reported values.
In the case of compounds with n = 2 and 3, we took
advantage of the fact that the bromo alkylsulfonate salts 2a
and 2b are commercially available and were thus able to
eliminate the sulfonation step of the bromoalkyl quaternary
bromide salts. In fact, the conversion of 2a and 2b with an
excess of 2-(dimethylamino)ethanol (1) in dimethylform-
Scheme 2. Synthetic route for the variation of the inner charge dis-
tance of sulfobetaine methacrylates. [a] n = 2 and 3. [b] n = 4, 5, 6,
8, and 12.
2
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Sulfobetaine Methacrylates with Varying Charge Distance
Table 2. Formation of the sulfobetaine alcohols (Step 2).
alternative approaches failed, including the reaction with
methacryloyl chloride or the use of coupling reagent strate-
gies such as N,N-dicyclohexylcarbodiimide (DCC)/4-(di-
methylamino)pyridine (DMAP).
Table 3. Formation of the sulfobetaine methacrylates (Step 3).
Entry
Starting material
n
Product
Yield [%]
1
2
3
4
5
3c
3d
3e
3f
4
5
6
8
12
4c
4d
4e
4f
85
77
78
80
72
3g
4g
Entry
Starting material
n
Product
Yield [%]
1
2
3
4
5
6
7
4a
4b
4c
4d
4e
4f
2
3
4
5
6
8
12
5a
5b
5c
5d
5e
5f
42
62
72
70
68
74
71
amide directly resulted in the formation of sulfobetaine
alcohols 4a and 4b. The products precipitated during the
reaction and were subsequently collected by filtration. Fur-
ther purification steps were not necessary. In case of com-
pounds with n Ͼ 3, sulfonation of the quaternary bromide
salts 3c–g with sodium sulfite in aqueous solution at 90 °C
for 24 h led to the formation of sulfobetaine alcohols 4c–g
in good yields. After removal of the solvent, the major part
of unreacted starting material could be removed by dissolv-
ing the crude products in small amounts of methanol und
subsequent precipitation in acetone. However, further puri-
fication of the products 4c–g by means of column
chromatography through a short column (silica, 10 cm)
using methanol as eluent was required. Even very small
amounts of the remaining starting materials 3c–g in the cor-
responding products resulted in spontaneous polymeriza-
tion of the methacrylic acid in the final esterification step.
It should be noted at this point that alternative synthetic
routes to the described sulfobetaine methacrylates tested in
our laboratories have proven to be less favorable. The con-
version of the 1,n-dibromoalkanes 2c–g with 2-(dimeth-
ylamino)ethyl methacrylate in a similar manner to Step 1,
followed by sulfonation of the obtained quaternary bromide
salts would make this route a general, two-step procedure.
Tested for n = 6, we found that the first step is simple to
perform, but unfortunately the final sulfonation resulted in
an attack of the double bond by the sulfite ion. In addition,
we tested the monosulfonation of 1,n-dibromoalkanes for n
Ͼ 4 according to a procedure published by Fujii and
Cook,[14] aiming for a further conversion of the obtained
bromoalkylsulfonates with 2-(dimethylamino)ethanol (1) in
the manner described above. Unfortunately, we were not
able to isolate the monosubstituted products in acceptable
yields.
4g
5g
However, we found that methacrylic acid is able to dis-
solve hydroxy intermediates 4a–g and simultaneous un-
dergo an esterification reaction after adding catalytic
amounts of sulfuric acid, leading to the target compounds
5a–g in high yields of up to 74%. In case of 5a, the maxi-
mum yield achieved was 42%, probably because of the
poorer solubility of the starting material 4a in methacrylic
acid compared to the other starting compounds. In general,
longer reaction times did not result in higher yields in all
cases. To prevent spontaneous and uncontrolled polymeri-
zation of the methacrylic acid and the formed sulfobetaine
methacrylates, small amounts of hydroquinone were added
to the reaction mixture. Although the polarity of the
hydroxy intermediates 4a–g and their corresponding prod-
ucts 5a–g are comparable, separation of the molecules by
means of classic column chromatography was easily con-
ducted by using mixtures of methanol and dichloromethane
as eluent. Monomers 5a–g are hygroscopic powders that
quickly adsorb water in air. Indeed, elemental analysis (C,
H, N, S) of the final products indicate the presence of water.
In general, the measured values for C, N, and S were
slightly lower, whereas the values for H were slightly higher
than the theoretical values. Taking into account the adsorp-
tion of about one molecule of water per monomer, the ob-
tained values were satisfactory.
The successful isolation of the sulfobetaine methacrylate
5g in good yields (also in the previous reaction steps) indi-
cates the applicability of our approach to the synthesis of
sulfobetaine methacrylates bearing a larger number of
methylene groups between the two charges.
The key step in the presented synthetic route is the final
acid-catalyzed esterification of the obtained sulfobetaine
alcohols 4a–g with methacrylic acid, leading to the corre-
sponding target compounds 5a–g (Table 3). The special fea-
ture of this step lies in the fact that methacrylic acid acts as
solvent as well as esterification reagent for the extremely
polar, and otherwise difficult to dissolve, sulfobetaine
Polymerization
The isolated sulfobetaine methacrylates are particularly
hydroxy intermediates. Due to the poor solubility of the interesting as monomeric precursors in fields of polymer
sulfobetaine alcohols in commonly used organic solvents, chemistry and materials science; however, applications in
all attempts to synthesize the target compounds through these fields presupposes polymerizability of the vinyl group.
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D. Kratzer, L. Barner, C. Friedmann, S. Bräse, J. Lahann
FULL PAPER
Hence, the synthetic value of our new approach was dem- analysis of polymer 6g are close to the calculated theoretical
onstrated by conventional free-radical polymerization of values, but also indicate the adsorption of water [elemental
the obtained sulfobetaine methacrylates. It should be analysis calcd. (%) for 6g: C 59.23, H 9.69, N 3.45, S 7.91;
mentioned that known compounds 5a–c, which were syn- found C 55.01, H 9.94, N 3.05, S 7.20]. In addition, the
thesized through alternative routes, have already been broad band at 3422 cm–1 in the IR spectrum of 6g indicated
successfully applied in controlled radical polymeriza- water adsorption. Poly(sulfobetaines) are known to quickly
tions.[5a,5b,12a,15]
absorb up to one molecule of water per betain unit in air
To demonstrate the polymerizability of the obtained because of their hygroscopic character.[10] The 1H NMR
monomers, we subjected compounds 5a–g to conditions spectrum of the reaction solution showed the presence of
typically used in conventional free-radical polymerizations. monomer 5g only. In this study, we were mainly focused on
Polymerizations were performed in 0.5 m aqueous sodium the development of the synthetic route, therefore no further
bromide solution at 70 °C for 150 min. using 2 mol-% 4,4Ј- attempts at optimizing the polymerization conditions for 5g
azobis(4-cyanopentanoic acid) as initiator. Monomer 5g were undertaken. Future steps will involve extensive studies
had to be polymerized in methanol because of its poor solu- that focus on the polymerization and application of the de-
bility in water. The obtained polyzwitterions were purified scribed new sulfobetaine methacrylates.
by dialysis against demineralized water and were further-
more analyzed by size-exclusion chromatography (see the
Supporting Information 1.4). Conversions were determined
by 1H NMR spectroscopic analysis of the reaction solution.
As expected from conventional free-radical polymeriza-
tions, the obtained polymers 6a–f showed a broad molec-
ular weight distribution and, therefore, high polydispersities
(Table 4).
Conclusions
We report a generic synthetic strategy for the systematic
preparation of a range of new sulfobetaine methacrylates in
good yields. The facile, three-step procedure allows for the
variation of the number of methylene groups between the
positive and the negative charge in the target compound by
suitable choice of the corresponding dibromoalkane in the
first step, under otherwise identical conditions. A special
feature of our approach is the final esterification of the ex-
tremely polar sulfobetaine hydroxy intermediates, in which
methacrylic acid acts as solvent as well as esterification rea-
gent. The universal nature of this new approach has been
demonstrated by synthesizing a series of sulfobetaine meth-
acrylates bearing two to twelve methylene groups between
the charges, from which the methacrylates bearing more
than four methylene groups (5d–g) have not previously been
reported. Furthermore, the synthetic value of the procedure
was demonstrated by conducting conventional free-radical
polymerization of the obtained monomers.
Table 4. Free-radical polymerization of the sulfobetaines.
Entry Monomer Polymer Mn [g/mol][a][b] Mw [g/mol][a][c] PDI[a][d]
1
2
3
4
5
6
7
5a
5b
5c
5d
5e
5f
6a
6b
6c
6d
6e
6f
67400
108300
116900
61700
95700
22700
n.a.
421300
510300
504000
533900
618600
333900
n.a.
6.30
4.70
4.30
8.70
6.50
14.7
n.a.
5g
6g
[a] Determined by size-exclusion chromatography. The SEC system
was calibrated against PEO standards with molecular weights (Mp)
ranging from 232 to 1,015,000 gmol–1. [b] Number average molec-
ular weight. [c] Weight average molecular weight. [d] Mw/Mn.
Although the applicability of the presented synthetic
strategy has only been tested for the maximum number of
twelve methylene groups between the two charges, the re-
sults indicate broad applicability for the synthesis of sulfo-
betaines. In addition, structural changes of the amino
alcohol nucleophile in the first step (e.g., a larger number
of carbon atoms between the O and the N atom) should
be compatible with the developed method. In general, our
synthetic strategy enables access to a library of new sulfo-
betaine methacrylates that are characterized by a wide
range of structural diversity. Controlled radical polymeriza-
tions of the described new monomers, especially surface-
initiated ATRP and RAFT polymerizations, are being per-
formed and the biological and physical properties of the
resulting polymers are under investigation in our laborato-
ries.
1
After the reaction, no monomer was detected in the H
NMR spectra of 6a–f and, therefore, the yields were as-
sumed to be quantitative. An interesting exception was
found in the case of polymer 6g, which precipitated from
the reaction mixture after 15 min reaction time. Surpris-
ingly, the obtained substance was insoluble in all commonly
used organic solvents (1,4-dioxane, dimethyl sulfoxide
(DMSO), CH2Cl2, ethanol, methanol, isopropyl alcohol
(IPA), tetrahydrofuran (THF), diethyl ether, acetone, ethyl
acetate, hexane) as well as water and aqueous sodium brom-
ide solution. Therefore, neither size-exclusion chromatog-
raphy nor NMR spectroscopic analysis could be conducted.
Elemental analysis and IR spectrum of polymer 6g did not
show any indication of a degradation reaction. The IR spec-
trum of polymer 6g revealed characteristic bands at 1168
and 1036 cm–1, representing asymmetric and symmetric
SO3 stretching, as well as a band at 1716 cm–1, indicative of
the carbonyl group. It also shows broadened bands com-
pared to the IR spectrum of its monomer 5g (see the Sup-
porting Information 1.3). The amounts of carbon,
Experimental Section
General Procedure A. Typical Procedure for the Formation of
hydrogen, nitrogen, and sulfur measured by elemental Bromoalkyl Quaternary Bromide Salts 3c–g (Table 1): In a 100 mL
4
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Sulfobetaine Methacrylates with Varying Charge Distance
two-neck flask, the corresponding 1,n-dibromoalkane 2c–g
(0.06 mol, 4.00 equiv.) was dissolved in acetone (60 mL) and heated
membrane (Sigma–Aldrich, cut-off 14000 Da) and were sub-
sequently dried by freeze-drying. The obtained polymers were ana-
to 45 °C. Then, 2-(dimethylamino)ethanol (1; 0.015 mol, lyzed by size-exclusion chromatography (SEC) with 0.5 m aqueous
1.00 equiv.) was added slowly to this mixture over a period of 6 h,
while stirring. The reaction mixture was then stirred for 18 h at
45 °C. After cooling to room temp., the white precipitation (double
alcohol) was removed by filtration. The liquid phase was evapo-
rated to remove the solvent and the oily residue was diluted with
ethyl acetate (150 mL). The product was extracted with water (3ϫ
100 mL) and the excess of the 1,n-dibromoalkane was recovered
from the organic phase. The aqueous phases were combined and
evaporated to give the corresponding bromoalkyl quaternary brom-
ide salt 3c–g as a yellowish oil.
NaBr solution/acetonitrile (80:20) (see the Supporting Infor-
mation).
4-Bromo-N-(2-hydroxyethyl)-N,N-dimethylbutane-1-ammonium
Bromide (3c): The reaction was carried out starting from 1,4-di-
bromobutane (2c) following General Procedure A, yield 2.83 g
(9.28 mmol, 62%); Rf = 0.05 (methanol). 1H NMR (500 MHz,
MeOD): δ = 4.00 (ddd, J = 7.64, 5.28, 2.75 Hz, 2 H, OCH2), 3.54
(t, J = 6.21 Hz, 2 H, BrCH2), 3.50–3.48 (m, 2 H, NCH3), 3.47–
3.44 (m, 2 H, NCH2), 3.18 (s, 6 H, 2ϫNCH2), 2.01–1.90 (m, 4 H,
CH2) ppm. 13C NMR (125 MHz, MeOD): δ = 66.71 (–, CH2),
65.71 (–, CH2), 56.90 (–, CH2), 52.32 (+, 2ϫNCH3), 32.98
General Procedure B. Typical Procedure for the Formation of Sulfo-
betaine Alcohols 4a–b: In a 250 mL flask, the corresponding so-
dium bromoalkylsulfonate 2a–b (25.0 mmol, 1.00 equiv.) was sus-
pended in dimethylformamide (70 mL) and heated to 70 °C. After
(–, CH ), 30.51 (–, CH ), 22.53 (–, CH ) ppm. FTIR (ATR): ν =
˜
2
2
2
3262 (m), 3006 (w), 2944 (w), 1490 (m), 1460 (m), 1420 (w), 1346
(w), 1326 (w), 1278 (w), 1236 (w), 1219 (w), 1146 (w), 1093 (w),
30 min, 2-(dimethylamino)ethanol (1; 100 mmol, 4.00 equiv.) was 1045 (w), 995 (m), 952 (w), 939 (w), 912 (m), 898 (m), 788 (m), 746
added and the mixture was stirred for 48 h at 70 °C. After cooling
to room temp., the precipitated product was filtered off and washed
with dimethylformamide (3ϫ 50 mL) and diethyl ether (3ϫ
50 mL). The product was dried in high vacuum for 3 h to give the
corresponding sulfobetaine alcohol 4a–b as a white solid.
(w), 649 (m), 600 (m), 529 (m) cm–1. MS (FAB): m/z (%) = 224.1
(100) [M – Br–]+, 162.1 (6), 154.1 (11), 136.1 (9). HRMS (FAB):
m/z calcd. for C8H19NOBr+ [M – Br–]+ 224.0645; found 224.0647
[M – Br–]+.
5-Bromo-N-(2-hydroxyethyl)-N,N-dimethylpentane-1-ammonium
Bromide (3d): The reaction was carried out starting from 1,5-di-
bromopentane (2d) following General Procedure A, yield 3.64 g
(11.4 mmol, 76%); Rf = 0.06 (methanol). 1H NMR (500 MHz,
MeOD): δ = 3.99 (br. s, 2 H, OCH2), 3.51–3.42 (m, 6 H, 2ϫNCH2,
BrCH2), 3.18 (s, 6 H, 2ϫNCH3), 1.98–1.92 (m, 2 H, CH2), 1.88–
1.81 (m, 2 H, CH2), 1.56–1.50 (m, 2 H, CH2) ppm. 13C NMR
(125 MHz, MeOD): δ = 66.58 (–, CH2), 66.56 (–, CH2), 56.30 (–,
CH2), 52.30 (+, 2ϫNCH3), 33.86 (–, CH2), 33.26 (–, CH2), 25.98
General Procedure C. Typical Procedure for the Formation of Sulfo-
betaine Alcohols 4c–g (Table 2): In a 50 mL two-neck flask
equipped with a reflux condenser, the corresponding bromoalkyl
quaternary bromide salt 3c–g (8.00 mmol, 1.00 equiv.) was dis-
solved in water (25 mL) and heated to reflux. After 10 min, sodium
sulfite (9.84 mmol, 1.24 equiv.) was added to this solution and the
reaction mixture was stirred and heated to reflux for 24 h. After
cooling to room temp., the solvent was removed under reduced
pressure and the white residue was dissolved in methanol (100 mL)
and the insoluble residue was filtered off. The solvent was concen-
trated to 5–10 mL under reduced pressure and the product was
precipitated in acetone (150 mL). The product was collected by fil-
tration, dried in high vacuum, absorbed on silica and subjected to
flash chromatography through a short column (10 cm silica; meth-
anol) to give the corresponding sulfobetaine alcohol 4c–g as a white
solid.
(–, CH ), 22.89 (–, CH ) ppm. FTIR (ATR): ν = 3292 (w), 3011
˜
2
2
(w), 2942 (w), 1628 (vw), 1465 (w), 1295 (vw), 1252 (w), 1226 (w),
1079 (w), 1008 (w), 968 (w), 921 (w), 736 (w), 639 (w), 556 (w) cm–1.
MS (FAB): m/z (%) = 238.1 (100) [M – Br–]+, 176.2 (10), 158.2
(10). HRMS (FAB): m/z calcd. for C9H21NOBr+ [M – Br–]+
238.0801; found 238.0800 [M – Br–]+.
6-Bromo-N-(2-hydroxyethyl)-N,N-dimethylhexane-1-ammonium
Bromide (3e): The reaction was carried out starting from 1,6-di-
bromohexane (2e) following General Procedure A, yield 3.75 g
General Procedure D. Typical Procedure for the Formation of Sulfo-
betaine Methacrylates 5a–g (Table 3): An oven-dried 50 mL two- (11.3 mmol, 75%); Rf = 0.09 (methanol). 1H NMR (500 MHz,
neck flask fitted with a reflux condenser was evacuated and back-
filled with argon and charged with the corresponding sulfobetaine
alcohol 4a–g (6.00 mmol) and hydroquinone (10 mg). Then meth-
acrylic acid (30 mL) was added and the mixture was heated to
70 °C while stirring. After 30 min, sulfuric acid (5 drops) was added
to this suspension and the reaction mixture was stirred for 48 h at
70 °C. After cooling to room temp., the liquid phase was separated
from the brown oily phase by decantation. The oily residue was
subsequently dried in vacuo, and the liquid phase was evaporated
until dry. Both residues were dissolved in methanol, combined, ab-
sorbed on silica, and subjected to flash chromatography (silica;
dichloromethane/methanol, 1:1) to give the corresponding sulfo-
betaine methacrylate 5a–g as a white solid.
MeOD): δ = 4.01–3.98 (m, 2 H, OCH2), 3.49–3.46 (m, 4 H, NCH2,
BrCH2), 3.44–3.40 (m, 2 H, NCH2), 3.17 (s, 6 H, 2ϫNCH3), 1.93–
1.87 (m, 2 H, CH2), 1.86–1.79 (m, 2 H, CH2), 1.59–1.53 (m, 2 H,
CH2), 1.45–1.38 (m, 2 H, CH2) ppm. 13C NMR (125 MHz,
MeOD): δ = 66.70 (–, CH2), 66.59 (–, CH2), 56.92 (–, CH2), 52.26
(+, 2ϫNCH3), 34.15 (–, CH2), 33.64 (–, CH2), 28.68 (–, CH2),
26.54 (–, CH ), 23.55 (–, CH ) ppm. FTIR (ATR): ν = 3288 (w),
˜
2
2
2932 (w), 2859 (w), 1463 (w), 1249 (w), 1081 (w), 1052 (w), 1010
(w), 968 (w), 924 (w), 731 (w), 637 (w), 555 (w) cm–1. MS (FAB):
m/z (%) = 252.2 (100) [M – Br–]+, 190.0 (7), 172.5 (12). HRMS
(FAB): m/z calcd. for C10H23NOBr+ [M – Br–]+ 252.0963; found
252.0966 [M – Br–]+.
8-Bromo-N-(2-hydroxyethyl)-N,N-dimethyloctane-1-ammonium
Bromide (3f): The reaction was carried out starting from 1,8-di-
bromooctane (2f) following General Procedure A, yield 4.34 g
(12.0 mmol, 80%); Rf = 0.09 (methanol). 1H NMR (500 MHz,
Polymerization: Polymers of the described zwitterionic methacryl-
ates were obtained by radical polymerization in degassed (freeze-
pump-thaw technique, 3 cycles) aqueous solutions (0.7 m monomer,
0.5 m sodium bromide) at 70 °C for 150 min, using 2 mol-% 4,4Ј- MeOD): δ = 3.99 (br. s, 2 H, OCH2), 3.50–3.39 (m, 6 H, 2ϫNCH2,
azobis(4-cyanopentanoic acid) (V 501) as initiator. Monomer 5g
was polymerized in methanol (0.2 m monomer) because of its poor
solubility in aqueous solution. Polymers were purified by dialysis
against demineralized water for 7 d using a dialysis tubing cellulose
BrCH2), 3.16 (s, 6 H, 2ϫNCH3), 1.89–1.77 (m, 4 H, CH2), 1.50–
1.35 (m, 8 H, 4ϫCH2) ppm. 13C NMR (125 MHz, MeOD): δ =
66.83 (–, CH2), 66.55 (–, CH2), 56.92 (–, CH2), 52.23 (+,
2ϫNCH3), 34.46 (–, CH2), 33.93 (–, CH2), 30.05 (–, CH2), 29.61
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
www.eurjoc.org
5

Job/Unit: O42734
/KAP1
Date: 03-11-14 15:03:01
Pages: 9
D. Kratzer, L. Barner, C. Friedmann, S. Bräse, J. Lahann
FULL PAPER
(–, CH2), 29.04 (–, CH2), 27.31 (–, CH2), 23.63 (–, CH2) ppm. CH2), 52.27 (+, 2ϫNCH3), 51.23 (–, CH2), 23.00 (–, CH2), 22.40
FTIR (ATR): ν = 3295 (w), 2926 (w), 2854 (w), 1628 (vw), 1463 (–, CH ) ppm. FTIR (ATR): ν = 3310 (m), 2931 (w), 1712 (vw),
˜
˜
2
(w), 1256 (vw), 1081 (w), 1051 (w), 964 (w), 724 (vw), 637 (w), 556 1485 (w), 1420 (w), 1384 (vw), 1341 (w), 1309 (w), 1193 (m), 1160
(w) cm–1. MS (FAB): m/z (%) = 280.2 (100) [M – Br–]+, 232.2 (14),
218.2 (14), 200.2 (25), 88.1 (10). HRMS (FAB): m/z calcd. for
C12H27NOBr+ [M – Br–]+ 280.1271; found 280.1269 [M – Br–]+.
(s), 1093 (m), 1074 (m), 1035 (s), 971 (m), 958 (m), 908 (w), 856
(m), 790 (m), 744 (w), 603 (s), 540 (m), 522 (m), 403 (m) cm–1. MS
(FAB): m/z (%) = 226.1 (100) [M + H]+, 154.1 (11), 136.1 (9).
HRMS (FAB): m/z calcd. for C8H20NO4S [M + H]+ 226.1108;
found 226.1105.
12-Bromo-N-(2-hydroxyethyl)-N,N-dimethyldodecane-1-ammonium
Bromide (3g): The reaction was carried out starting from 1,12-di-
bromododecane (2g) following General Procedure A, yield 5.26 g
(12.6 mmol, 84 %); Rf = 0.08 (methanol). 1H NMR (500 MHz,
5-[(2-Hydroxyethyl)dimethylammonio]pentane-1-sulfonate (4d): The
reaction was carried out starting from 5-bromo-N-(2-hydroxy-
MeOD): δ = 4.00–3.97 (m, 2 H, OCH2), 3.49–3.38 (m, 6 H, ethyl)-N,N-dimethylpentane-1-ammonium bromide (3d) and fol-
2ϫNCH2, BrCH2), 3.16 (s, 6 H, 2ϫNCH3), 1.87–1.76 (m, 4 H, lowing General Procedure C, yield 1.47 g (6.16 mmol, 77%); Rf =
2ϫCH2), 1.46–1.33 (m, 16 H, 8ϫCH2) ppm. 13C NMR (125 MHz, 0.13 (methanol). H NMR (500 MHz, MeOD): δ = 4.00–3.97 (m,
1
MeOD): δ = 66.87 (–, CH2), 66.55 (–, CH2), 56.92 (–, CH2), 52.22
(+, 2ϫNCH3), 34.50 (–, CH2), 34.04 (–, CH2), 30.63 (–, CH2),
2 H, OCH2), 3.47–3.45 (m, 2 H, NCH2), 3.42–3.39 (m, 2 H,
NCH2), 3.16 (s, 6 H, 2ϫNCH3), 2.85–2.82 (m, 2 H, CH2SO3),
30.61 (–, 2ϫCH2), 30.56 (–, CH2), 30.25 (–, CH2), 29.88 (–, CH2), 1.89–1.80 (m, 4 H, 2ϫCH2), 1.55–1.49 (m, 2 H, CH2) ppm. 13C
29.20 (–, CH2), 27.45 (–, CH2), 23.69 (–, CH2) ppm. FTIR (ATR): NMR (125 MHz, MeOD): δ = 66.56 (–, CH2), 66.54 (–, CH2),
ν = 3235 (m), 3021 (w), 2913 (m), 2847 (m), 1738 (vw), 1462 (m), 56.90(–,CH2),52.23(+,NCH3),52.20(+,NCH3),51.98(–,CH2),26.28
˜
1374 (w), 1268 (w), 1208 (w), 1091 (m), 1071 (w), 1043 (w), 1008 (–, CH ), 25.47 (–, CH ), 23.20 (–, CH ) ppm. FTIR (ATR): ν =
˜
2
2
2
(w), 981 (w), 981 (w), 962 (m), 885 (w), 855 (w), 828 (vw), 759 (vw),
3291 (w), 3032 (vw), 2936 (w), 2852 (w), 1465 (w), 1203 (m), 1159
726 (w), 653 (w), 604 (w), 547 (w), 514 (w), 489 (w), 450 (w) cm–1. (s), 1082 (m), 1030 (s), 975 (w), 946 (w), 926 (w), 887 (w), 794 (w),
MS (FAB): m/z (%) = 336.2 (100) [M – Br–]+, 256.2 (10), 88.0 (7).
HRMS (FAB): m/z calcd. for C16H35NOBr+ [M – Br–]+ 336.1897;
found 336.1898 [M – Br–]+.
685 (w), 604 (m), 535 (m), 524 (m) cm–1. MS (FAB): m/z (%) =
240.1 (100) [M + H]+, 158.2 (11), 88.1 (7). HRMS (FAB): m/z
calcd. for C9H22NO4S [M + H]+ 240.1264; found 240.1265.
2-[(2-Hydroxyethyl)dimethylammonio]ethanesulfonate (4a): The re-
action was carried out starting from sodium 2-bromoethanesulfon-
ate (2a) following General Procedure B, yield 2.21 g (11.2 mmol,
6-[(2-Hydroxyethyl)dimethylammonio]hexane-1-sulfonate (4e): The
reaction was carried out starting from 6-bromo-N-(2-hydroxy-
ethyl)-N,N-dimethylhexane-1-ammonium bromide (3e) and follow-
1
45%); Rf = 0.18 (methanol). H NMR (500 MHz, D2O): δ = 4.09–
ing General Procedure C, yield 1.58 g (6.24 mmol, 78%); Rf = 0.15
1
4.06 (m, 2 H, OCH2), 3.82–3.79 (m, 2 H, CH2), 3.57–3.55 (m, CH2), (methanol). H NMR (500 MHz, MeOD): δ = 4.00–3.97 (m, 2 H,
3.48–3.45 (m, CH2), 3.22 (s, 6 H, 2 ϫ NCH3) ppm. 13C NMR OCH2), 3.47–3.45 (m, 2 H, NCH2), 3.42–3.38 (m, 2 H, NCH2),
(125 MHz, D2O): δ = 66.48 (–, CH2), 60.24 (–, CH2), 55.36 (–, 3.15 (s, 6 H, 2ϫNCH3), 2.82–2.79 (m, 2 H, CH2SO3), 1.85–1.78
CH ), 51.75 (+, 2ϫNCH ), 44.25 (–, CH ) ppm. FTIR (ATR): ν (m, 4 H, 2ϫCH2), 1.57–1.51 (m, 2 H, CH2), 1.45–1.39 (m, 2 H,
˜
2
3
2
= 3383 (w), 3250 (w), 1672 (w), 1494 (vw), 1466 (w), 1367 (vw),
CH2) ppm. 13C NMR (125 MHz, MeOD): δ = 66.68 (–, CH2),
1286 (vw), 1181 (m), 1094 (w), 1037 (m), 1001 (w), 936 (w), 896 66.55 (–, CH2), 56.91 (–, CH2), 52.27 (–, CH2), 52.20 (+, NCH3),
(vw), 803 (w), 773 (w), 720 (w), 661 (w), 606 (w), 546 (w), 504 (w), 52.18 (+, NCH3), 28.84 (–, CH2), 26.78 (–, CH2), 25.58 (–, CH2),
457 (w) cm–1. MS (FAB): m/z (%) = 198.1 (100) [M + H]+, 155.0 23.18 (–, CH ) ppm. FTIR (ATR): ν = 3299 (w), 2927 (w), 2861
˜
2
(10), 154.0 (35), 136.0 (24), 107.0 (7).
(w), 1483 (w), 1467 (w), 1202 (m), 1162 (m), 1081 (w), 1034 (m),
975 (w), 930 (w), 907 (w), 775 (w), 649 (w), 605 (m), 571 (w), 536
(w), 523 (m) cm–1. MS (FAB): m/z (%) = 254.5 (100) [M + H]+,
132.3 (40). HRMS (FAB): m/z calcd. for C10H24NO4S [M + H]+
254.1426; found 254.142.
3-[(2-Hydroxyethyl)dimethylammonio]propane-1-sulfonate (4b): The
reaction was carried out starting from sodium 2-bromopropane-
1-sulfonate (2b) and following General Procedure B, yield 4.75 g
1
(22.5 mmol, 90%). H NMR (500 MHz, D2O): δ = 4.07–4.04 (m,
2 H, OCH2), 3.57–3.53 (m, 4 H, 2ϫCH2), 3.18 (s, 6 H, 2ϫNCH3), 8-[(2-Hydroxyethyl)dimethylammonio]octane-1-sulfonate (4f): The
2.98 (t, J = 7.3 Hz, 2 H, CH2SO3), 2.28–2.22 (m, 2 H, OCH2) ppm. reaction was carried out starting from 8-bromo-N-(2-hydroxy-
13C NMR (125 MHz, D2O): δ = 65.03 (–, CH2), 63.34 (–, CH2),
ethyl)-N,N-dimethyloctane-1-ammonium bromide (3f) and follow-
55.25 (–, CH2), 51.36 (+, 2 ϫ NCH3), 47.21 (–, CH2), 18.18 (–, ing General Procedure C, yield 1.80 g (6.40 mmol, 80%); Rf = 0.15
CH ) ppm. FTIR (ATR): ν = 3323 (w), 3025 (vw), 2928 (vw), 1475
(methanol). 1H NMR (500 MHz, MeOD): δ = 3.98 (br. s, 2 H,
˜
2
(w), 1352 (w), 1306 (vw), 1242 (w), 1194 (m), 1171 (m), 1080 (m),
OCH2), 3.47–3.45 (m, 2 H, NCH2), 3.41–3.37 (m, 2 H, NCH2),
1041 (m), 963 (w), 936 (w), 900 (w), 844 (vw), 794 (w), 763 (w), 3.15 (s, 6 H, 2ϫNCH3), 2.80–2.77 (m, 2 H, CH2SO3), 1.84–1.76
721 (w), 647 (w), 598 (m), 558 (w), 523 (m), 504 (w), 451 (w) cm–1.
MS (FAB): m/z (%) = 212.1 (24) [M + H]+, 154.1 (100) [3NBA],
137.1 (65), 136.1 (58), 120.1 (8), 107.1 (14), 89.1 (11). HRMS
(FAB): m/z calcd. for C7H18NO4S [M + H]+ 212.0949; found
212.0951.
(m, 4 H, 2ϫCH2), 1.49–1.35 (m, 4 H, 2ϫCH2) ppm. 13C NMR
(125 MHz, MeOD): δ = 66.80 (–, CH2), 66.51 (–, CH2), 56.92 (–,
CH2), 52.57 (–, CH2), 52.20 (+, 2ϫNCH3), 29.84 (–, CH2), 29.69
(–, CH2), 29.40 (–, CH2), 27.16 (–, CH2), 25.86 (–, CH2), 23.47 (–,
CH ) ppm. FTIR (ATR): ν = 3298 (w), 3031 (vw), 2925 (w), 2845
˜
2
(vw), 1613 (vw), 1474 (w), 1288 (vw), 1194 (w), 1163 (m), 1092 (w),
1031 (m), 973 (w), 943 (w), 914 (w), 856 (vw), 783 (w), 754 (vw),
725 (vw), 589 (w), 544 (w), 520 (w), 439 (vw), 410 (m) cm–1. MS
(FAB): m/z (%) = 282.2 (100) [M + H]+, 200.2 (9), 154.1 (31), 136.1
(22), 107.1 (9), 81.1 (9). HRMS (FAB): m/z calcd. for C12H28NO4S
[M + H]+ 282.1734; found 282.1733.
4-[(2-Hydroxyethyl)dimethylammonio]butane-1-sulfonate (4c): The
reaction was carried out starting from 4-bromo-N-(2-hydroxy-
ethyl)-N,N-dimethylbutane-1-ammonium bromide (3c) and follow-
ing General Procedure C, yield 1.53 g (6.79 mmol, 85%); Rf = 0.14
(methanol). 1H NMR (500 MHz, MeOD): δ = 4.00 (ddd, J = 7.46,
5.14, 2.68 Hz, 2 H, OCH2), 3.47–3.42 (m, 4 H, 2ϫNCH2), 3.15 (s,
6 H, 2ϫNCH3), 2.88 (t, J = 7.19 Hz, 2 H, CH2SO3), 2.02–1.95 (m, 12-[(2-Hydroxyethyl)dimethylammonio]dodecane-1-sulfonate (4g):
2 H, CH2), 1.83 (q, J = 7.46, 7.45 Hz, 2 H, CH2) ppm. 13C NMR
The reaction was carried out starting from 12-bromo-N-(2-
(125 MHz, MeOD): δ = 66.63 (–, CH2), 66.26 (–, CH2), 56.90 (–, hydroxyethyl)-N,N-dimethyldodecane-1-ammonium bromide (3g)
6
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42734
/KAP1
Date: 03-11-14 15:03:01
Pages: 9
Sulfobetaine Methacrylates with Varying Charge Distance
and following General Procedure C, yield 1.94 g (5.76 mmol, 72%);
Rf = 0.14 (CH2Cl2/MeOH, 2:1). H NMR (500 MHz, MeOD): δ = 3.79–3.77 (m, 2 H, NCH2), 3.50–3.47 (m, 2 H, NCH2), 3.20 (s, 6
4.00–3.97 (m, 2 H, OCH2), 3.47–3.45 (m, 2 H, NCH2), 3.41–3.38 H, 2ϫNCH3), 2.90 (t, J = 7.3 Hz, 2 H, CH2SO3), 2.05–1.98 (m,
(m, 2 H, NCH2), 3.15 (s, 6 H, 2 ϫ NCH3), 2.79–2.76 (m, 2 H,
CH2SO3), 1.83–1.75 (m, 4 H, 2 ϫ CH2), 1.44–1.33 (m, 16 H, (125 MHz, MeOD): δ = 167.69 (Cquat, C=O), 137.13 (Cquat
8ϫCH2) ppm. 13C NMR (125 MHz, MeOD): δ = 66.87 (–, CH2), C=CH2), 127.37 (–, C=CH2), 66.13 (–, CH2), 64.02 (–, CH2), 59.14
C=CH2), 5.75–5.74 (s, 1 H, C=CH2), 4.65–4.64 (m, 2 H, OCH2),
1
5 H, CH2, C=CCH3), 1.89–1.83 (m, 2 H, CH2) ppm. 13C NMR
,
66.52 (–, CH2), 56.92 (–, CH2), 52.73 (–, CH2), 52.19 (+,
2ϫNCH3), 30.23 (–, 2ϫCH2), 30.20 (–, CH2), 30.08 (–, 2ϫCH2),
(–, OCH2), 51.96 (+, 2ϫNCH3), 51.28 (–, CH2), 23.02 (–, CH2),
22.39 (–, CH ), 18.43 (+, C=CCH ) ppm. FTIR (ATR): ν = 3032
˜
2
3
30.00 (–, CH2), 29.58 (–, CH2), 27.34 (–, CH2), 25.89 (–, CH2), (vw), 1713 (w), 1637 (vw), 1468 (w), 1314 (w), 1184 (m), 1151 (m),
23.59 (–, CH ) ppm. FTIR (ATR): ν = 3420 (w), 3298 (w), 2961 1035 (m), 929 (w), 808 (w), 723 (w), 607 (w), 537 (w), 522 (m), 404
˜
2
(vw), 2914 (w), 2846 (w), 1638 (vw), 1482 (w), 1463 (w), 1354 (vw),
1215 (w), 1171 (m), 1096 (m), 1072 (w), 1039 (m), 1004 (w), 986
(w), 970 (w), 924 (w), 791 (w), 601 (m), 540 (w), 521 (m), 450
(vw) cm–1. MS (FAB): m/z (%) = 294.2 (94) [M + H]+, 212.3 (23),
156.3 (8). 113.3 (100) [M – C6H14NSO3]+. HRMS (FAB): m/z calcd.
for C12H24NO5S [M + H]+ 294.1375; found 294.1377. C12H23NO5S
(w) cm–1. MS (FAB): m/z (%) = 338.2 (100) [M + H]+, 256.4 (11), (293.38): calcd. C 49.13, H 7.90, N 4.77, S 10.93; found C 48.76,
154.3 (9), 89.4 (10). HRMS (FAB): m/z calcd. for C16H36NO4S [M H 7.91, N 4.61, S 10.66.
+ H]+ 338.2365; found 338.2368.
5-{[2-(Methacryloyloxy)ethyl]dimethylammonio}pentane-1-sulfonate
2-{[2-(Methacryloyloxy)ethyl]dimethylammonio}ethanesulfonate
(5a): The reaction was carried out starting from 2-[(2-hydroxyeth-
yl)dimethylammonio]ethanesulfonate (4a) and following General
(5d): The reaction was carried out starting from 5-[(2-hydroxyeth-
yl)dimethylammonio]pentane-1-sulfonate (4d) and following Gene-
ral Procedure D, yield 1.29 g (4.20 mmol, 70%); Rf = 0.13 (CH2Cl2/
Procedure D, yield 669 mg (2.52 mmol, 42%); Rf = 0.21 (CH2Cl2/ MeOH, 1:1). 1H NMR (500 MHz, MeOD): δ = 6.15 (s, 1 H,
MeOH, 1:1). 1H NMR (500 MHz, D2O): δ = 6.17 (s, 1 H, C=CH2), C=CH2), 5.73 (m, 1 H, C=CH2), 4.62 (br. s, 2 H, OCH2), 3.76–
5.78 (s, 1 H, C=CH2), 4.66 (br. s, 2 H, OCH2), 3.86–3.81 (m, 4 H, 3.74 (m, 2 H, NCH2), 3.44–3.40 (m, 2 H, NCH2), 3.18 (s, 6 H,
2ϫNCH2), 3.50–3.47 (m, 2 H, CH2SO3), 3.26 (s, 6 H, 2ϫNCH3), 2 ϫ NCH3 ), 2.84–2.81 (m, 2 H, CH2 SO3 ), 1.97 (s, 3 H,
1.94 (s, 3 H, H2C=CCH3) ppm. 13C NMR (125 MHz, D2O): δ =
H2C=CCH3), 1.89–1.81 (m, 4 H, 2ϫ CH2), 1.55–1.51 (m, 2 H,
168.37 (Cquat, C=O), 135.05 (Cquat, C=CH2), 127.76 (–, C=CH2), CH2) ppm. 13C NMR (125 MHz, MeOD): δ = 167.68 (Cquat, C=O),
63.04 (–, CH2), 60.36 (–, CH2), 58.30 (–, CH2), 51.45 (+,
2 ϫNCH3), 44.13 (–, CH2), 17.25 (+, H2C=CCH3) ppm. FTIR
137.13 (Cquat, C=CH2), 127.37 (–, C=CH2), 66.44 (–, CH2), 63.91
(–, CH2), 59.09 (–, CH2), 51.94 (–, CH2), 51.90 (+, 2ϫNCH3),
26.27 (–, CH2), 25.49 (–, CH2), 23.19 (–, CH2), 18.42 (+,
(ATR): ν = 1705 (m), 1632 (w), 1486 (w), 1458 (w), 1319 (w), 1297
˜
(w), 1282 (w), 1207 (m), 1189 (m), 1156 (w), 1123 (m), 1063 (w),
1037 (m), 963 (w), 940 (w), 910 (w), 819 (w), 767 (m), 652 (vw),
H C=CCH ) ppm. FTIR (ATR): ν = 3434 (w), 2964 (vw), 1712
˜
2 3
(m), 1638 (vw), 1469 (w), 1368 (vw), 1323 (w), 1298 (w), 1262 (vw),
620 (m), 598 (m), 540 (w), 524 (m), 475 (w), 458 (w) cm–1. MS 1171 (s), 1034 (m), 974 (w), 952 (w), 921 (w), 902 (w), 816 (w), 787
(FAB): m/z (%) = 266.1 (100) [M + H]+, 184.1 (5), 154.1 (9), 114.1
(9), 113.1 (100) [M – C4H10NSO3]+, 95.1 (6). HRMS (FAB): m/z
(w), 730 (w), 654 (vw), 600 (m), 545 (w), 522 (m), 483 (w) cm–1.
MS (FAB): m/z (%) = 308.2 (100) [M + H]+, 240.1 (7), 226.2 (7),
calcd. for C10H20NO5S [M + H]+ 266.1062; found 266.1059. 154.0 (10), 113.0 (27) [M – C7H16NSO3]+. HRMS (FAB): m/z calcd.
C10H19NO5S (265.32): calcd. C 45.27, H 7.22, N 5.28, S 12.09;
found C 44.19, H 7.23, N 5.20, S 11.90.
for C13H26NO5S [M + H]+ 308.1526; found 308.1524. C13H25NO5S
(307.41): calcd. C 50.79, H 8.20, N 4.56, S 10.43; found C 49.43,
H 8.07, N 4.33, S 10.33.
3-{[2-(Methacryloyloxy)ethyl]dimethylammonio}propane-1-sulfonate
(5b): The reaction was carried out starting from 3-[(2-hydroxyeth-
yl)dimethylammonio]propane-1-sulfonate (4b) and following Gene-
ral Procedure D, yield 1.04 g (3.72 mmol, 62%); Rf = 0.15 (CH2Cl2/
6-{[2-(Methacryloyloxy)ethyl]dimethylammonio}hexane-1-sulfonate
(5e): The reaction was carried out starting from 6-[(2-hydroxyeth-
yl)dimethylammonio]hexane-1-sulfonate (4e) and following Gene-
MeOH, 1:1). 1H NMR (500 MHz, D2O): δ = 6.17 (s, 1 H, C=CH2), ral Procedure D, yield 1.31 g (4.08 mmol, 68%); Rf = 0.14 (CH2Cl2/
5.79 (s, 1 H, C=CH2), 4.65 (t, J = 2.2 Hz, 2 H, OCH2), 3.84–3.82 MeOH, 1:1). 1H NMR (500 MHz, MeOD): δ = 6.16–6.15 (m, 1 H,
(m, 2 H, NCH2), 3.61–3.58 (m, 2 H, NCH2), 3.23 (s, 6 H,
2ϫNCH3), 2.98 (t, J = 7.3 Hz, 2 H, CH2SO3), 2.31–2.23 (m, 2 H,
C=CH2), 5.74–5.73 (m, 1 H, C=CH2), 4.63–4.61 (m, 2 H, OCH2),
3.76–3.74 (m, 2 H, NCH2), 3.44–3.40 (m, 2 H, NCH2), 3.17 (s, 6
CH2), 1.95 (s, 3 H, H2C=CCH3) ppm. 13C NMR (125 MHz, D2O): H, 2 ϫ NCH3), 2.82–2.79 (m, 2 H, CH2SO3), 1.97 (s, 3 H,
δ = 168.42 (Cquat, C=O), 135.14 (Cquat, C=CH2), 127.70 (–, H2C=CCH3), 1.86–1.78 (m, 4 H, 2ϫ CH2), 1.57–1.51 (m, 2 H,
C=CH2), 63.43 (–, CH2), 62.51 (–, CH2), 58.34 (–, CH2), 51.25 (+,
2 ϫ NCH3 ), 47.19 (–, CH2 ), 18. 24 (–, CH2 ), 17.25 (+, MeOD): δ = 167.69 (Cquat, C=O), 137.15 (Cquat, C=CH2), 127.35
H C=CCH ) ppm. IR (ATR): ν = 3450 (vw), 1722 (w), 1634 (vw), (–, C=CH2), 66.56 (–, CH2), 63.88 (–, CH2), 59.11 (–, CH2), 52.25
CH2), 1.45–1.39 (m, 2 H, CH2) ppm. 13C NMR (125 MHz,
˜
2
3
1455 (vw), 1423 (vw), 1322 (vw), 1302 (w), 1215 (w), 1160 (m), (–, CH2), 51.90 (+, 2ϫNCH3), 28.86 (–, CH2), 26.78 (–, CH2),
1036 (m), 957 (w), 904 (w), 817 (vw), 798 (w), 720 (vw), 601 (w), 25.58 (–, CH2), 23.18 (–, CH2), 18.41 (+, H2C=CCH3) ppm. FTIR
529 (m), 457 (w) cm–1. MS (FAB): m/z (%) = 280.2 (100) [M +
H]+, 217.2 (4), 176.1 (4), 166.1 (6), 136.2 (48), 113.2 (20) [M –
C5H12NSO3]+, 107.2 (13), 89.2 (10). HRMS (FAB): m/z calcd. for
(ATR): ν = 3411 (w), 3036 (w), 2935 (w), 2862 (w), 1723 (m), 1642
(w), 1466 (w), 1321 (w), 1182 (s), 1159 (s), 1033 (s), 958 (w), 930
(m), 882 (m), 799 (m), 746 (m), 727 (m), 606 (s), 523 (m), 488
˜
C11H22NO5S [M + H]+ 280.1219; found 280.1216. C11H21NO5S (w) cm–1. MS (FAB): m/z (%) = 322.2 (100) [M + H]+, 240.3 (16),
(279.35): calcd. C 47.29, H 7.58, N 5.01, S 11.48; found C 44.34, 113.4 (94) [M – C8H18NSO3]+. HRMS (FAB): m/z calcd. for
H 7.99, N 4.62, S 10.79.
C14H28NO5S [M + H]+ 322.1688; found 322.1686. C14H27NO5S
(321.43): calcd. C 52.31, H 8.47, N 4.36, S 9.98; found C 49.69, H
8.30, N 3.82, S 10.01.
4-{[2-(Methacryloyloxy)ethyl]dimethylammonio}butane-1-sulfonate
(5c): The reaction was carried out starting from 4-[(2-hydroxyeth-
yl)dimethylammonio]butane-1-sulfonate (4c) and following Gene-
ral Procedure D, yield 1.27 g (4.32 mmol, 72%); Rf = 0.13 (CH2Cl2/
8-{[2-(Methacryloyloxy)ethyl]dimethylammonio}octane-1-sulfonate
(5f): The reaction was carried out starting from 8-[(2-hydroxyeth-
MeOH, 1:1). 1H NMR (500 MHz, MeOD): δ = 6.18 (s, 1 H, yl)dimethylammonio]octane-1-sulfonate (4f) and following General
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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Job/Unit: O42734
/KAP1
Date: 03-11-14 15:03:01
Pages: 9
D. Kratzer, L. Barner, C. Friedmann, S. Bräse, J. Lahann
FULL PAPER
Procedure D, yield 1.55 g (4.44 mmol, 74%); Rf = 0.18 (CH2Cl2/
MeOH, 1:1). 1H NMR (500 MHz, MeOD): δ = 6.15 (s, 1 H,
C=CH2), 5.73 (s, 1 H, C=CH2), 4.62 (br. s, 2 H, OCH2), 3.75–3.74
(m, 2 H, NCH2), 3.42–3.38 (m, 2 H, NCH2), 3.17 (s, 6 H,
2 ϫ NCH3 ), 2.80–2.77 (m, 2 H, CH2 SO3 ), 1.97 (s, 3 H,
H2C=CCH3), 1.85–1.75 (m, 4 H, 2ϫ CH2), 1.50–1.35 (m, 8 H,
Acknowledgments
The authors acknowledge funding from the Karlsruhe Institute of
Technology (KIT) and the Helmholtz Association through the
BioInterfaces Programme. The authors also thank Birgit Huber
(Soft Matter Synthesis Laboratory) for the purification and analy-
sis of the polymers.
4ϫCH2) ppm. 13C NMR (125 MHz, MeOD): δ = 167.69 (Cquat
,
C=O), 137.14 (Cquat, C=CH2), 127.36 (–, C=CH2), 66.66 (–, CH2),
63.82 (–, CH2), 59.10 (–, CH2), 52.52 (–, CH2), 51.91 (+,
2ϫNCH3), 29.76 (–, CH2), 29.65 (–, CH2), 29.31 (–, CH2), 27.14
( – , C H 2 ) , 2 5 . 7 9 ( – , C H 2 ) , 2 3 . 4 7 ( – , C H 2 ) , 1 8 . 4 1 ( + ,
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a) A. B. Lowe, C. L. McCormick, Chem. Rev. 2002, 102, 4177–
4190; b) A. Laschewsky, Polymers 2014, 6, 1544–1601; c) S.
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A. Mathis, B. Meurer, Y. M. M. Soto, J. C. Galin, Polymer
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H C=CCH ) ppm. FTIR (ATR): ν = 2923 (w), 2854 (w), 1717 (m),
˜
2
3
1638 (vw), 1466 (w), 1293 (w), 1173 (s), 1035 (m), 967 (w), 938
(w), 915 (w), 843 (vw), 811 (w), 787 (w), 725 (w), 663 (vw),
603 (m), 542 (w), 523 (m) cm–1. MS (FAB): m/z (%) = 350.2 (100)
[M + H]+, 268.2 (15), 156.1 (8), 114.1 (9), 113.1 (90) [M –
C10H22NSO3]+. HRMS (FAB): m/z calcd. for C16H32NO5S [M +
H]+ 350.1996; found 350.1994. C16H31NO5S (349.48): calcd. C
54.99, H 8.94, N 4.01, S 9.17; found C 51.09, H 9.40, N 3.69, S
8.56.
[2]
[3]
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[5]
J. B. Schlenoff, Langmuir 2014, 30, 9625–9636.
12-{[2-(Methacryloyloxy)ethyl]dimethylammonio}dodecane-1-sulf
onate (5g): The reaction was carried out starting from 12-[(2-
hydroxyethyl)dimethylammonio]dodecane-1-sulfonate (4g) and fol-
lowing General Procedure D, yield 1.73 g (4.26 mmol, 71%); Rf =
0.28 (CH2Cl2/MeOH, 1:1). 1H NMR (500 MHz, MeOD): δ = 6.16–
6.15 (m, 1 H, C=CH2), 5.74–5.72 (m, 1 H, C=CH2), 4.62–4.60 (m,
2 H, OCH2), 3.76–3.74 (m, 2 H, NCH2), 3.43–3.39 (m, 2 H,
NCH2), 3.17 (s, 6 H, 2ϫNCH3), 2.79–2.76 (m, 2 H, CH2SO3), 1.97
(s, 3 H, H2C=CCH3), 1.83–1.76 (m, 4 H, 2ϫCH2), 1.44–1.33 (m,
16 H, 8ϫCH2) ppm. 13C NMR (125 MHz, MeOD): δ = 167.69
(Cquat, C=O), 137.15 (Cquat, C=CH2), 127.34 (–, C=CH2), 66.66 (–,
CH2), 63.79 (–, CH2), 59.12 (–, CH2), 52.74 (–, CH2), 51.92 (+,
2ϫNCH3), 30.26 (–, 2ϫCH2), 30.11 (–, 2ϫCH2), 30.08 (–, CH2),
29.61 (–, 2ϫCH2), 27.36 (–, CH2), 25.90 (–, CH2), 23.61 (–, CH2),
a) Z. Zhang, S. Chen, Y. Chang, S. Jiang, J. Phys. Chem. B
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muir 1991, 7, 854–867.
[12] a) Y. Terayama, M. Kikuchi, M. Kobayashi, A. Takahara,
Macromolecules 2011, 44, 104–111; b) T. A. Wielema,
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18.43 (+, H C=CCH ) ppm. FTIR (ATR): ν = 2918 (m), 2846 (w),
˜
2
3
1715 (m), 1636 (w), 1484 (m), 1466 (m), 1303 (m), 1206 (m), 1178
(s), 1037 (m), 952 (m), 908 (w), 850 (w), 815 (w), 793 (w), 782 (w),
725 (w), 663 (w), 603 (m), 542 (m), 522 (m), 492 (w) cm–1. MS
(FAB): m/z (%) = 406.1 (100) [M + H]+, 324.2 (8), 154.3 (9), 113.4
(34) [M
–
C14H30NSO3]+. HRMS (FAB): m/z calcd. for
C20H40NO5S [M + H]+ 406.2627; found 406.2629. C20H39NO5S
(405.59): calcd. C 59.23, H 9.69, N 3.45, S 7.91; found C 57.53, H
9.72, N 3.14, S 7.78.
Supporting Information (see footnote on the first page of this arti-
cle): Experimental details, analytical equipment, GPC data analysis
1
of the zwitterionic polymers, as well as H and 13C NMR spectra
Received: June 10, 2014
of all compounds.
Published Online: ᭿
8
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© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
Eur. J. Org. Chem. 0000, 0–0

Job/Unit: O42734
/KAP1
Date: 03-11-14 15:03:01
Pages: 9
Sulfobetaine Methacrylates with Varying Charge Distance
Polymeric Zwitterions
D. Kratzer, L. Barner, C. Friedmann,
S. Bräse, J. Lahann* ......................... 1–9
A Synthetic Route to Sulfobetaine Meth-
acrylates with Varying Charge Distance
A simple and highly universal three-step
procedure has been developed for the syn-
thesis of sulfobetaine methacrylates with
variation of the charge separation distance.
The protocol provides access to a library of
new zwitterionic precursors that have po-
tential for a range of applications in poly-
mer chemistry and materials science.
Keywords: Synthetic methods / Materials
science / Surfactants / Zwitterions / Poly-
merization
Eur. J. Org. Chem. 0000, 0–0
© 0000 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
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