Synthesis and application of novel degradable crosslinkers

Article abstract of DOI:10.1016/j.cclet.2010.10.028

A novel divinyl ether was synthesized by a convenient method with high yield. Then the divinyl ether was combined with 2-hydroxyethyl methacrylate and acrylic acid, respectively, generating difunctional polymeric crosslinkers with (hemi)acetal structure t

Full text of DOI:10.1016/j.cclet.2010.10.028

Available online at www.sciencedirect.com
Chinese Chemical Letters 22 (2011) 374–377
www.elsevier.com/locate/cclet
Synthesis and application of novel degradable crosslinkers
*
Xin Ce Sui, Zhi Feng Fu, Yan Shi
State Key Laboratory of Chemical Resource Engineering, Beijing University of Chemical Technology, Beijing 100029, China
Received 12 July 2010
Available online 22 December 2010
Abstract
A novel divinyl ether was synthesized by a convenient method with high yield. Then the divinyl ether was combined with 2-
hydroxyethyl methacrylate and acrylic acid, respectively, generating difunctional polymeric crosslinkers with (hemi)acetal
structure that was labile in acid. The chemical structures of the divinyl ether and crosslinkers were confirmed by 1H NMR
and elemental analysis. The crosslinkers were employed in free-radical polymerization to prepare polymer gel and gel particles.
Due to the (hemi)acetal structure in the crosslinking segment, the polymer gel and particles exhibited degradable ability in strong
acid.
# 2010 Yan Shi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
Keywords: Divinyl ether; Crosslinker; Degradation
The intelligent gels, such as pH-sensitive gels, had been widely investigated due to their special characters [1]. The
general pH-sensitive polymer gels exhibit swelling or deswelling as pH changed [2], but pH does not alter their
chemical compositions or molecular structures. So the pH-sensitive polymer gels with special component that will
decompose in selective media attracted great attention for the biomedical materials [3] and electronics industry [4].
Because of the decomposability in acid, the acetal components, such as poly(1,3-dioxolane), have been used to prepare
crosslinkers for the degradable gels [5,6]. However, the cationic polymerization of 1,3-dioxolane was performed under
rigorous conditions and the purification must be carried out at low temperature to remove the cyclic species. The acetal
components could also be obtained by the addition reaction of the hydroxyl and vinyloxyl groups in the presence of an
acidic catalyst [7]. In the other way, vinyloxyl groups could react with carboxyl group without catalyst, generating
hemiacetal compounds that were also labile in acid [8]. Thus, the degradable crosslinkers could be obtained by the
addition reaction of divinyl ethers with hydroxyl or carboxyl functionalized polymeric monomers, such as 2-
hydroxyethyl methacrylate (HEMA) or acrylic acid (AA). However, most commercial divinyl ethers synthesized by
the reaction of acetylene and diols were expensive because of the low conversions, rigorous conditions and complex
separation process [9].
The aim of the present work was: (1) to prepare divinyl ethers under mild condition with high conversion and
convenient separation process; (2) to generate degradable crosslinkers by the reaction of the divinyl ethers with AA or
HEMA, as shown in Scheme 1. When the crosslinkers were employed with the common commercial monomers,
* Corresponding author.
E-mail address: shiyan@mail.buct.edu.cn (Y. Shi).
1001-8417/$ – see front matter # 2010 Yan Shi. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.
doi:10.1016/j.cclet.2010.10.028

[()TD$FIG]
X.C. Sui et al. / Chinese Chemical Letters 22 (2011) 374–377
375
Scheme 1. Synthesis of degradable crosslinkers with (hemi)acetal structure: (a) AA; (b) HEMA.
degradable networks could be obtained via free-radical polymerization. Furthermore, since the crosslinkers were
based on (meth)acrylate, they might have potential application in reworkable UV curing materials [10].
The divinyl ethers were synthesized through the reaction of 4-hydroxybutyl vinyl ether (HBVE) and diisocyanates,
such as diphenylmethane diisocyanate (MDI). In a well-dried round-bottom flask with magnetic stirring, HBVE and
MDI with the feeding ratio of 2:1 were dissolved in tetrahydrofuran (THF) under the protection of nitrogen. The
reaction took place at 50 8C, generating a divinyl ether bis[4-(vinyloxy)butyl](methylenedi-4,1-phenylene)-
biscarbamate (BMCT). The content of isocyanate group in the system was monitored by a reaction of the sample with
an excess of di-n-butylamine in acetone, and then the excess di-n-butylamine was determined by back-titration with
standard hydrochloric acid [11]. The conversion of isocyanate group reached 99% for 12 h. The product was obtained
by twice precipitation in a large amount of hexane from THF solution, dried under vacuum and stored at room
temperature. The chemical structure of BMCTwas determined by 1H NMR analysis and elemental analysis. 1H NMR
(600 MHz, CDCl3): d 7.28 (d, 4H, J = 10.2 Hz) 7.10 (d, 4H, J = 8.4 Hz), 6.58 (s, 2H), 6.47 (m, 2H, J = 7.0 Hz), 4.18 (t,
4H, J = 5.7 Hz), 4.16 (d, 2H, J = 1.8 Hz), 3.99 (dd, 4H, J = 7.2, 2.4 Hz), 3.88 (s, 2H), 3.71 (t, 4H, J = 5.7 Hz), 1.77 (m,
8H, J = 6.0 Hz). Anal. Calcd. for BMCT (C27H34N2O6): C 67.22; H 7.05; N 5.81. Found: C 66.92; H 7.27; N 5.96. The
BMCT was white solid powder, and the yield was about 95%.
The (meth)acrylate crosslinkers were prepared by the addition reaction of BMCTwith HEMA or AA in a well-dried
round-bottom flask with magnetic stirring, using THF as solvent. An excess molar amount of HEMA/AA relative to
BMCT (MolBMCT/MolHEMA/AA = 1:4) was fed to achieve the maximal conversion of BMCT. The reaction of BMCT
with HEMA proceeded in the presence of a trace amount of catalyst pyridinium p-toluenesulfonate (PTS) and inhibitor
4-tert-butylcatechol at 30 8C for 8 h, generating bis{4-[1-(2-methacryloyloxy)ethoxy]ethoxy-butyl}(methylenedi-
4,1-phenylene) biscarbamate (BMBE). The reaction of BMCT with AA took place in the absence of catalyst but
inhibitor at 70 8C for 8 h, generating bis[4-(1-acryloyloxy)ethoxybutyl](methylenedi-4,1-phenylene)biscarbamate
(BABE). The products were washed by a large amount of hexane, dried under vacuum and stored at 4 8C. They were
both yellow viscous liquid, and the yields were about 97%.
1
Fig. 1(A) depicts the H NMR spectrum of BMBE. The singles at d 6.11 and 5.61 (peak a, b) corresponded to
protons of the C–C double bond. The peaks at d 7.49, 7.14 and 3.87 (peak c–e) resulted from BMCT units, and
belonged to the aromatic and diphenyl methylene protons. The characteristic peak of the acetal methine proton was
present at d 4.67 (peak f), and its integral intensity (If) was exactly equal to Ia, demonstrating that a difunctional
[()TD$FIG]
Fig. 1. 1H NMR spectra (in acetone-d6) of the two crosslinkers. (A) BMBE; (B) BABE.

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Table 1
Synthesis and hydrolysis of PMMA gels via solution polymerization.
a
b
TC (h)
c
TH (min)
d
TH (min)
Gel
Crosslinker
BABE
f
SR
G-1
G-2
G-3
G-4
1:4
1:8
1:8
1:16
1.5
2.0
2.5
4.0
8.72
7.33
7.80
6.48
60
40
50
30
480
390
420
330
BMBE
a
Feeding ratio of the crosslinker and MMA by weight.
Crosslinking time.
b
c
d
Time needed for complete hydrolysis of gel when treated with HCl (0.1 mol/L).
Time needed for complete hydrolysis of gel when treated with HCl (10ꢀ3 mol/L).
Table 2
Synthesis and hydrolysis of PMMA gel particles via suspension polymerization.
a
b
TH (min)
c
TH (min)
Particle
Crosslinker
f
SR
P-1
P-2
BABE
BMBE
1:8
1:8
3.41
3.27
80
720
960
120
a
Feeding ratio of the crosslinker and MMA by weight.
b
c
Time needed for complete hydrolysis of swollen particles when treated with HCl (0.1 mol/L).
Time needed for complete hydrolysis of swollen particles when treated with HCl (10ꢀ3 mol/L).
crosslinker with acetal structure was obtained by the reaction of BMCT with HEMA. Anal. Calcd. for BMBE
(C39H54N2O12): C 63.07; H 7.28; N 3.77. Found: C 62.79; H 7.47; N 3.88. Fig. 1(B) depicts the 1H NMR spectrum of
BABE. The peaks corresponding to C–C double bond protons were present at d 6.35, 6.15 and 5.90 (peak a–c). The
characteristic peak of the hemiacetal methine proton was present at d 4.67 (peak g), and its integral intensity (Ig) was
exactly equal to Ia, indicating that a difunctional crosslinking agent with hemiacetal structure was also obtained
successfully. Anal. Calcd. for C33H42N2O10 (BABE): C 63.26; H 6.71; N 4.47. Found: C 63.02; H 6.83; N 4.56.
The polymeric property of the two crosslinkers was investigated by free-radical polymerization with methyl
methacrylate (MMA) using solution and suspension technique, as shown in Tables 1 and 2, respectively. In a typical
experiment of solution polymerization, MMA and BABE were dissolved in THF in a round-bottom flask equipped
with a magnetic stirrer, using 2,20-azobisisobutyronitrile (AIBN) as initiator. The system was degassed with three
freeze–evacuate–thaw cycles. The polymerization was performed under argon atmosphere at 70 8C in an oil bath. A
polymer gel generated in the flask after the stirrer failed in running, and the crosslinking time, i.e. the time needed for
the entire gelation process, depended on the type and content of crosslinker. Then the gel was washed by THF in a
Soxhlet extractor for 24 h, and no sol fraction was detected in the extracting solvent that indicated a complete gel
formation. After the extraction, the THF-equilibrated network was weighed. Then the swollen network was vacuum-
dried at room temperature for 48 h and reweighed. The swelling ratio (SR) of the network was calculated with Eq. (1).
In a typical suspension polymerization, BMBE and AIBN were dissolved in MMA and then introduced into a
poly(vinyl alcohol) (PVA, 0.05 wt%) aqueous solution in a round-bottom flask equipped with a mechanical stirrer and
a condenser. The polymerization proceeded at 70 8C for 8 h under the protection of nitrogen. No sol fraction was
detected in the extracting solvent after the particles were extracted in THF for 24 h. The SR of the particles was
determined according to literature [12]: the particles were placed in a stainless steel mesh and immersed in THF for
36 h. The particles and mesh were picked up from THF together, drained for 1 min, tapped with filter paper, and
weighed. The SR were calculated with Eq. (1):
Ws ꢀ Wd
SR ¼
(1)
Wd
where Ws is weight of swollen network/gel particles and Wd is weight of dried network/gel particles.
The polymer gel and particles were swollen in THF for 36 h at room temperature and then treated with a small
amount of HCl (0.1/10ꢀ3/10ꢀ5 mol/L), NaOH aqueous solution (0.1 mol/L), or deionized water, respectively. The
swollen gel and particles remained unchanged in a strong alkali, water or diluted acid (HCl, 10ꢀ5 mol/L). When

[()TD$FIG]
X.C. Sui et al. / Chinese Chemical Letters 22 (2011) 374–377
377
Fig. 2. GPC chromatograms of the polymers of hydrolyzed gels and particles. (A) gels; (B) particles.
treated with a strong acid (HCl, 0.1/10ꢀ3 mol/L), the network disappeared gradually and a clear solution formed
finally. Moreover, less time was needed for the hydrolyzing process when the gel/particles was treated in the stronger
acid environment. The clear solution was neutralized to pH 7, and then poured into a large excess of hexane for
precipitation. The copolymerization behavior of the monomers and crosslinking agents could be obtained indirectly by
studying the soluble residual linear chains. Fig. 2 shows the gel permeation chromatography (GPC) traces of polymers
of hydrolyzed gels and particles. The molecular weights of the backbones were larger when BABE was used as
crosslinker than BMBE in solution polymerization systems, but lower in suspension polymerization system.
In summary, a novel divinyl ether was prepared under mild condition with high conversion and convenient
separation process. The divinyl ether then reacted with HEMA or AA, generating difunctional polymeric crosslinkers
with (hemi)acetal structure that were able to degrade in acid. The polymeric character of the degradable crosslinkers
was investigated in free-radical polymerization via solution and suspension technique, and the obtained polymer gel
and gel particles behaved degradation in strong acid environment.
References
[1] A. Horta, M.J. Molina, M.R. Gomez-Anton, Macromolecules 42 (2009) 1285.
[2] L.Y. Peddada, N.K. Harris, D.I. Devore, et al. J. Control. Release 140 (2009) 134.
[3] M.D. Timmer, H. Shin, R.A. Horch, et al. Biomacromolecules 4 (2003) 1026.
[4] K. Ogino, J.S. Chen, C.K. Ober, Chem. Mater. 10 (1998) 3833.
[5] R.R. De Clercq, E.J. Goethals, Macromolecules 25 (1992) 1109.
[6] J. Du, X. Ding, Z. Zheng, et al. Eur. Polym. J. 38 (2002) 1033.
[7] T. Hashimoto, A. Umehara, M. Urushisaki, et al. J. Polym. Sci. Part A Polym. Chem. 42 (2004) 2766.
[8] H. Otsuka, T. Endo, Macromolecules 32 (1999) 9059.
[9] R.L. Zimmerman, G.D. Jones, W.R. Nummy, IEC Prod. Res. Dev. 2 (1963) 296.
[10] M. Shirai, Prog. Org. Coat. 58 (2007) 158.
[11] K. Gisselfalt, B. Edberg, P. Flodin, Biomacromolecules 3 (2002) 951.
[12] E.U. Kulawardana, D.C. Neckers, J. Polym. Sci. Part A Polym. Chem. 48 (2010) 55.