Multifunctional monomers based on vinyl sulfonates and vinyl sulfonamides for crosslinking thiol-Michael polymerizations: Monomer reactivity and mechanical behavior

Article abstract of DOI:10.1039/c8cc00782a

Multifunctional vinyl sulfonates and vinyl sulfonamides were conveniently synthesized and assessed in thiol-Michael crosslinking polymerizations. The monomer reactivities, mechanical behavior and hydrolytic properties were analyzed and compared with those of analogous thiol-acrylate polymerizations. Materials with a broad range of mechanical properties and diverse hydrolytic stabilities were obtained.

Full text of DOI:10.1039/c8cc00782a

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Multifunctional monomers based on vinyl
sulfonates and vinyl sulfonamides for crosslinking
thiol-Michael polymerizations: monomer reactivity
and mechanical behavior†
Cite this:DOI: 10.1039/c8cc00782a
Received 30th January 2018,
Accepted 28th February 2018
a
ab
a
a
Jasmine Sinha, Maciej Podgorski, Sijia Huang and Christopher N. Bowman
*
DOI: 10.1039/c8cc00782a
´
rsc.li/chemcomm
1
4
Multifunctional vinyl sulfonates and vinyl sulfonamides were the decoration of aminated polymers,
in the synthesis
1
5
conveniently synthesized and assessed in thiol-Michael crosslinking of dendrimers, and in the construction of biofunctional
polymerizations. The monomer reactivities, mechanical behavior molecules. The incorporation of vinyl sulfones results in the
and hydrolytic properties were analyzed and compared with those formation of a stable thioether sulfone bond as compared to its
of analogous thiol–acrylate polymerizations. Materials with a broad acrylate counterpart which results in a labile thioether ester
range of mechanical properties and diverse hydrolytic stabilities bond. Also, the sulfonamide bonds are observed to be extremely
1
6
1
7
1
8
were obtained.
stable, which makes sulfonamide conjugates useful for applica-
tions where the molecular stability is important.
However, there are no reports on neat thiol-Michael network
1
9
The growing demand for the convenient synthesis of diverse types
of photopolymerizable monomers with inherent novelty of the materials that incorporate vinyl sulfonates or vinyl sulfonamides as
molecule architectures has provided numerous opportunities to monomers, least to mention the properties attainable from such
explore the thiol-Michael addition as a click reaction, specifically thiol–vinyl combinations. Meanwhile, due to the poor electro-
for photopolymerizations and other network-forming reactions. negativity of methacrylates, multifunctional acrylates are the
Progress achieved by utilizing anion-mediated thiol–vinyl additions most common Michael acceptors implemented in thiol-Michael
was summarized in recent work and reviews devoted to thiol- crosslinking systems to date. However, they are limited in the
1
–4
Michael reactions and applications.
The highly exploitable range of material properties achieved. Further, the presence of
features of this reaction such as orthogonality with radical esters in the resulting polymer, particularly the hydrolytically
reactions, impressive reactivity in various media, and general unstable thioether ester resulting from the thiol–acrylate reaction,
simplicity of synthesis and implementation have made it a popular is also found to be a limiting factor with respect to the mechanical
tool. Complementing the thiol reactants, Michael acceptors have performance of these materials. Therefore, a need still exists
included electron-deficient vinyls such as acrylates, methacrylates, to explore the efficiency and versatility of Michael acceptors
5–8
acrylamides, vinyl sulfones, and malemides.
these, the vinyl sulfone group as a Michael acceptor has attracted suitable Michael-acceptors with tunable reactivities.
a great deal of attention due to its stability in aqueous media, In this communication, we introduce the vinyl sulfonate and
Amongst all of which can be introduced by structurally modifying enes to enable
biocompatibility and excellent reactivity towards thiols under vinyl sulfonamide groups in designing multifunctional Michael
9
relatively mild conditions. However, except for divinyl sulfone, acceptors and exploit their features by systematic study of vinyl
there are few if any other non-crystalline, multivinyl sulfone reactivity, followed by implementation in thiol-Michael cross-
monomers commercially available or readily synthesized for use linked polymeric materials. A broad diversity in the mechanical
1
0,11
in crosslinking polymerizations. Recently, vinyl sulfonates
and vinyl sulfonamides
and hydrolytic properties of the resultant network polymers has thus
1
2,13
have also been employed as Michael been achieved. Firstly, we synthesized vinyl sulfonate and vinyl
acceptors, most frequently as monofunctional reactants, in sulfonamide based monomers from inexpensive multifunctional
alcohols and amines, respectively, following a synthetic methodology
based on the substitution of the corresponding alcohols (Table 1)
a
Department of Chemical and Biological Engineering, University of Colorado,
and amines (Table 2) with 2-chloroethanesulfonyl chloride in the
Boulder, CO, USA. E-mail: Christopher.bowman@colorado.edu
Department of Polymer Chemistry, Faculty of Chemistry, MCS University,
Gliniana St. 33, Lublin 20-614, Poland
10
presence of Et N. To examine the reaction kinetics perfor-
b
3
mance of the new vinyl compounds, the relative reactivities of
the vinyl sulfonate and vinyl sulfonamide functional groups were
compared with other model compounds. 1-Hexyl acrylate (HA),
†
Electronic supplementary information (ESI) available. See DOI: 10.1039/
c8cc00782a
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Table 1 Synthesis of vinyl sulfonates 4a–g from multifunctional alcohols
a,b
1
a–g with 2-chloroethanesulfonyl chloride
Fig. 1 Vinyl conversions for the model thiol-Michael addition reactions.
Reactions were initiated with UV light in the range of 320–390 nm,
ꢀ2
1
0 mW cm turned on after 1 min, and continued for 10 min.
of these groups were found to be much more reactive than an
acrylate (Fig. 1). The relative rates of the Michael addition to
a,b-unsaturated sulfonate, sulfone, acrylate ester, and amides
could be related by considering the electrophilicity of the enoyl
b-carbon, which accounts for the energy of the transition state
which then leads to the formation of an enolate intermediate
upon addition of the nucleophile to the Michael acceptor.
Recently, Reddick et al. demonstrated the relative reactivity of
a
All reactions were carried out with 1 (1 mmol), 3 (1.1 mmol) and Et
3
N
b
(
3 mmol). Dichloromethane was used as the solvent for alcohols 1a–f
and tetrahydrofuran was used as the solvent for alcohol 1g.
0
Table 2 Synthesis of vinyl sulfonamides 7a–e from multifunctional Michael reactions of 2 -(phenethyl)thiol with vinyl sulfones,
a,b
amines 5a–e with 2-chloroethanesulfonyl chloride.
vinyl sulfonate esters, and vinyl sulfonamides relevant to vinyl
sulfonyl cysteine protease inhibitors. Indeed, the mechanistic
behavior could also be interpreted by electronic effects arising
from the linked oxygen or nitrogen atoms of the sulfonate ester
and sulfonamide groups. The presence of these group introduces
3
an inductive effect, wherein the poor sp /d orbital can overlap
between the oxygen or nitrogen and the sulfur, precluding an
electron-donating resonance effect. Therefore, the sulfonate ester
group is expected to introduce a strong inductive s-electron
withdrawing effect which would then be expected to stabilize
20
a-carbanion formation. Such an interpretation accurately explains
the reasoning for the higher reactivity of vinyl sulfonate as a
Michael acceptor as compared to the conventional acrylates
and vinyl sulfones. It has been well reported in the literature
that primary vinyl sulfonamides are particularly unreactive in
aza-Michael reactions. This behavior has been ascribed to the
deprotonation of the acidic sulfonamide protons to a certain
extent which leads to a reduction in the electrophilicity.
The lower reactivity of the vinyl sulfonamide as compared to
a
3
All reactions were carried out with 5 (1 mmol), 3 (1.1 mmol) and Et N
b
(2.1 mmol). Dichloromethane was used as the solvent in all cases.
1
-hexyl vinyl sulfonate (HVS), 1-hexyl acrylamide (HAA), 1-hexyl
vinyl sulfonamide (HVSA), and ethyl vinyl sulfone (EVS) were vinyl sulfonate could be attributed to the lower electronegativity
2
1
purchased (or synthesized) and reacted with butyl 3-mercapto- of the nitrogen as compared to oxygen. At the same time,
propionate (BMP) in model compound studies, wherein the the vinyl sulfonamide reacts more rapidly than acrylamide, for
vinyl (thiol) conversion during the irradiation was monitored similar reasons as indicated for the reactivity of the vinyl
using real-time Fourier transform infrared (FTIR) spectroscopy. sulfonates relative to acrylates.
The photo thiol-Michael model reactions were performed in
Initiation of polymerizations in bulk, solventless conditions
2
M solution of ethylene glycol diethyl ether as the solvent of was also conducted for various model monomeric systems.
ꢀ
1
choice with NPPOC-TMG photobase (20 mg mL ) at a thiol-to- Specifically, mixtures of thiols with either vinyl sulfonates or
vinyl stoichiometric ratio of 1 : 1. The vinyl conversion kinetic vinyl sulfones were cured by using thermal initiation (80 1C,
2
2
profiles are shown in Fig. 1.
TEMPO, 1–2 wt%) whereas mixtures incorporating other vinyls
The initial kinetic studies demonstrated that the vinyl sulfonate were cured photochemically with NPPOC-TMG (2 wt%) as a
is even more reactive than the vinyl sulfone group where both photobase. Thermal polymerizations were implemented because
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the inherent basicity of the photobase did not allow time-stable Table 3 Glass transition temperature results for neat thiol-Michael net-
works. All samples were prepared from mixtures containing equivalent
compositions to be formed from the two most reactive vinyls.
amount of thiol and vinyl functional groups. Values in parentheses represent
Before any mechanical testing, all compositions were thermally
standard deviations of three replicates
postcured (100 1C for 1 h) to assure complete functional
group conversions. Exemplary real-time kinetic profiles for Acrylates with
photocuring of DMHDVSA/PETMP and DMHDVSA/SiTSH are in
Vinyl sulfonates with
PETMP (T /1C)
Vinyl sulfonamide
(T /1C)
PETMP (T /1C)
g
g
g
the ESI,† in Fig. S1. These, as well as other photo-thiol-Michael EGDA ꢀ5.1(0.8)
EGDVS 35(2)
HDDVS 43(3)
TEGDVS 11(0.8)
TCDDVS 45(0.7)
TMPTVS 50(2)
GTVS 58(3)
HMDVSA/PETMP 46(3)
HMDVSA/SiTSH 58(6)
DMHDVSA/PETMP 34(1)
DMHDVSA/SiTSH 29(3)
DMPDVSA/SiTSH 57(0.6)
HPDVSA/SiTSH 95(0.3)
HDDA ꢀ9(0)
systems exhibited nearly identical characteristic kinetic behavior
TEGDA ꢀ15.7(0.8)
for both reactive groups, suggesting a stoichiometric reaction.
TCDDA 22(1)
Because the synthesized vinyl sulfonates were found to be quite TMPTA 22.4(0)
GTA 23(2)
reactive (and unstable) with thiols in the presence of NPPOC-TMG,
i.e., with quantities less than 0.5 wt% catalyst gelation was
observed only 30 s after photobase addition, their reactivity was
also probed in radical thiol–ene reactions (ESI,† Fig. S2b).
Unexpectedly, radical thiol–vinyl sulfonate reactions were also
found to proceed exceptionally well. Although, these systems are
less reactive than their radical thiol–acrylate counterparts, they
still reach high conversions with less than 10% off-stoichiometric
ene consumption as measured at the end of irradiation. For
example, HDDA/PETMP when cured radically results in 100%
conversion of acrylate and 66% thiol conversion whereas HDDVS/
PETMP cured analogously reaches 95% vinyl conversion and 87%
thiol conversion (ESI,† Fig. S2a and b). Contrary to observations
of the thiol–vinyl sulfonates, the thiol–vinyl sulfones and thiol–
vinyl sulfonamides are sluggish reactions when initiated
radically. More off-stoichiometric ene consumption and low
functional group conversions were measured in these systems
(ESI,† Fig. S2c and d). Therefore, even though the thiol–vinyl
sulfonate reaction is too reactive to initiate with the photobase
used here, it is readily photoinitiated (radically), resulting in
materials with equivalent or improved mechanical properties as
compared to those resulting from a stoichiometrically reacting
thiol-Michael system (compare DMA ESI† results).
Network polymers were prepared from neat stoichiometric
mixtures (per functional group concentration) of a commercial
thiol PETMP and an ester free thiol SiTSH and reacted with the
synthesized multifunctional vinyl sulfonate and vinyl sulfonamide
derivatives. These results were then compared with analogous
acrylate derivatives. Using divinyl Michael acceptors, representative
DMA plots were obtained for a range of new materials showing
g
the differences in T values between structurally analogues
Fig. 2 Storage modulus and tan delta data with neat PETMP as the thiol
thiol–vinyl systems, i.e. thiol–acrylate, thiol–vinyl sulfonate, monomer (a) acrylate (PETMP–HDDA), vinyl sulfonate (PETMP/HDDVS),
and thiol–vinyl sulfonamide (secondary and tertiary amides). vinyl sulfonamide (21 amine) (PETMP–HMDVSA) and vinyl sulfonamide
(
31 amine) (PETMP–DMHDVSA). (b) SiTSH as ester-free thiol monomer in
As can be seen from Table 3 and Fig. 2, thiol–vinyl sulfonate
HDDVS/PETMP) and thiol–vinyl sulfonamide based on the
primary amine (HMDVSA/PETMP) both exhibited similar and
significantly higher T ’s than the HDDA/PETMP. As reported
thiol–vinyl sulfonamide network polymers. The monomer ratios are: thiol :
vinyl = 1 : 1 based on the functional group content.
(
g
8
previously, the incorporation of sulfone groups with their networks showed similar property enhancements when compared
dipole–dipole interactions improve the mechanical performance to analogous acrylates. Furthermore, in the case of the thiol–
of these materials. Additionally, with the incorporation of a rigid sulfonamide network polymer incorporating the secondary amide
bicyclic core as in TCDDVS/PETMP or by increasing the overall (HMDVSA/PETMP), a higher T was measured than in the network
g
monomer functionality as in TMPTVS/PETMP or GTVS/PETMP, incorporating a tertiary amide (DMHDVSA/PETMP).
the resultant thiol–vinyl sulfonate network polymers were expected
This difference could be attributed to the presence of an amide
to exhibit further thermomechanical enhancement as compared proton in the secondary sulfonamide group that participates in
with analogously crosslinked thiol–acrylates. Indeed, as in hydrogen bonding along with the oxygen atom of the sulfonamide
2
3
the sulfone-based networks, the sulfonate and sulfonamide participating in C–Hꢁ ꢁ ꢁO interactions. As reported in the
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Table 4 Hydrolytic properties of a series of thiol-Michael polymers
material science disciplines. One extraordinary feature of these
materials is an impressive tunability of the hydrolytic properties
of thiol-Michael networks. Ranging from photo-, to thermally
degradable and non-degradable macromolecular architectures,
useful functional materials can be facilely fabricated fulfilling
the existing gaps in applied polymer and material science.
We gratefully acknowledge financial support from National
Institutes of Health for this research (NIH: 1U01DE023777-01)
Sample mass change
after 7 days in
5 wt% HCl
Sample mass change
after 7 days in
5 wt% NaOH
Thiol-Michael
network
HDDA/PETMP
ꢀ0.7 (0.3)
24 (8)
1.8 (1.1)
1.0 (0.4)
ꢀ15.1 (1)
HDDVS/PETMP
HMDVSA/PETMP
DMHDVSA/PETMP
Hydrolyzed in 1 day
Hydrolyzed in 10 min
0 (0)
literature, the elimination, or reduction in the amount, of
esters in the network results in higher Tg materials. It is Conflicts of interest
therefore expected that incorporation of ester-free thiol monomers
There are no conflicts to declare.
in mixtures with vinyl sulfonamides would also yield hydrolytically
22
stable, tough and glassy polymers. Accordingly, we introduced a
shorter chain length tertiary vinyl sulfonamide (DMPDVSA/SiTSH)
and structurally rigid cyclic vinyl sulfonamide (HPDVSA/SiTSH)
into the mixtures with the ester free thiol SiTSH. The resulting
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