Synthesis of Network Polymers from Multifunctional Aromatic Thiol Compounds

Network polymers have been synthesized by means of catalyst free thiol-yne reaction of multi-functional aromatic ethynyle and thiol compounds, 1,3,5-triethynylbenzenen (TEB), 1,4-diethynylbenzene (DEB), 1,4-benzenedithiol (BDT) and benzenethiol (BT). The network polymers of TEB/DEB-BDT or TEB-BDT/BT were obtained in good yields. The feed ratio of DEB or BT increased the chloroform solution, fragments, of the network polymers. The fragments of the network polymers showed optical properties derived from conjugation units of phenyl-ethynyl-sulﬁde. The network polymers have been synthesized by oxidation reaction of multi-functional aromatic thiol compounds, 1,3,5-benzene trithiol (BTT) with BDT or 4,4’-biphenyl dithiol (BPDT), accompanied by formation of disulﬁde bonds. The BTT network was degradable by a reductant, tris(2-caboxyethyl)phosphine hydrochloride.

Thiol group is known as one of the highly reactive groups in the synthetic chemistry. Thiol-ene reaction initiated by a radical is one of the usable click reactions. Sulfa-Michael addition reaction is another reaction with the chemicals with thiol group. These reactions have been widely used to synthesize small molecules but also polymer materials. 1,2 Aromatic thiol compounds show higher reactivity than the non-aromatic thiol compounds. Thiol-yne reaction between the aromatic thiol compounds with aromatic ethynylene compounds occurred without any catalysts nor initiators under the ambient reaction conditions. 3 In the case of the thiol-ene reaction between thiol and vinyl monomers initiated by a radical, the radical polymerization of the vinly monomer would occur as a side reaction. The high reactive thiol-yne reaction must be suitable to synthesize the polymers without formation of byproducts. The reactions form phenylene-vinylene with thiol, which should be usable to arrange features of the π-conjugation units. Development of the π-conjugation polymers have been widely investigated by modification of phenylene units to increase the solubility in solvents or control of emission wave length of the polymers. There must be possible limitation in this method to prepare the phenylene-based monomers with desired modified groups and/or to polymerize the monomers due to the steric hindrance. Incorporation of sulfide in the π-conjugation units by the thiol-yne reaction should be one of the effective methods to develop the π-conjugated polymers.
Oxidation between the thiol groups forms disulfide bound, which plays important roles in bio chemistry accompanied by redox reactions. The aromatic thiol compounds also show higher activity in the reaction than the non-aromatic thiol compounds, and must be usable for the applications.
We have developed joint-linker type gels, which were synthesized by thiol-ene click reaction of (non-aromatic) multi-functionalized thiol compounds, as the joint molecule, and diacrylate compounds, as the linker molecules in some organic solvents. 4 We also synthesized joint crosslinking gels by the oxidation of (non-aromatic) multifunctionalized thiol compounds accompanied by formation of the disulfide bounds. 5 The gels turned to solutions by reduction, and reformed the gels by oxidation of the solutions. As the next step, we came to an idea to synthesize the network polymers using the high activity of the aromatic thiol compounds. We have tried to synthesize the joint linker type network polymers by the non-catalytic thiol-yne reaction of multi-functional aromatic thiol and ethylene compounds, * Electrochemical Society Member. z E-mail: nnaga@sic.shibaura-it.ac.jp as shown in Scheme 1. Linearity and fragmentation of the network structure, controlled by co-polymerization, affected the solubility of the resulting polymers. Chloroform solution of the network polymers showed optical properties derived from π-conjugation units. The joint crosslinking network polymers were synthesized by oxidation (co-) polymerization of the multi-functional aromatic thiol compounds in dimethyl sulfoxide at ambient reaction temperature for short reaction time, as shown in Scheme 2. The resulting network polymers were degradable by a reductant accompanied by the cleavage of the disulfide bonds in the network structure.  sulfoxide (DMSO, Kanto Chemical Co., Inc.), methanol (MeOH, Kanto Chemical Co., Inc.), and chloroform (Kanto Chemical Co., Inc.) were commercially obtained from Kanto Chemical Co., Inc., and used as received.

Synthesis of TEB-BDT based network polymers.-
The molar ratio of ethynyl group in TEB and/or DEB to S-H group in BDT and/or BT was adjusted to 1.0. TEB (0.1 mmol), BDT (0.15 mmol), and THF (1.0 mL) were added to a 20 mL vial. The reaction stirred at room temperature for 24 h. The reaction mixture was poured into large excess of MeOH, and the precipitate was corrected by filtration, then washed with MeOH for several times. The obtained polymer was dried in vacuo. at room temperature for 6 h. TEB/DEB-BDT network polymers and TEB-BDT/BT network polymers were synthesized by the same procedures. (1.03 g) and DMSO (0.327 mL) wer introduced to a 10 mL ample tube. After the ample tube was sealed by burning off, the reaction system was heated at 50°C for 10 min. The reaction mixture was poured into large excess of MeOH, and the precipitate was corrected by filtration, then washed with MeOH for several times. The obtained polymer was dried in vacuo. at 60°C for 6 h. BTT-BDT (50 wt%-50 wt%) network polymer and BTT-BPDT (50 wt%-50 wt%) network polymer were synthesized by the same procedures. Analytical procedures.-FT-IR spectra of network polymers were recorded on a Jasco FT/IR-410 (JASCO Corporation). The samples were prepared as KBr tablets, and 30 scans were accumulated from 4000 to 500 cm −1 . 1 H NMR spectra of linker molecules or reaction systems (solution samples) were recorded on a JEOL-JNM-LA300 spectrometer in pulse Fourier transform mode. Molecular weight and molecular weight distribution of the polymers were measured at 40°C by means of gel permeation chromatography (GPC), Shimadzu Prominence GPC System, using chloroform as solvent and calibrated with standard polystyrene samples. UV-vis absorption spectroscopy of the chloroform soluble faction of the network polymer was conducted with Shimadzu UV-1600PC. Photoluminescence (PL) spectrum of the solution was recorded on a Shimadzu RF-1500, exited at the maximum absorption wave length of the solution sample.

TEB(/DEB)-BDT(/BT) network polymers.-TEB/DEB-BDT
network polymers were synthesized by the catalyst free thiol-yne reaction of TEB, DEB and BDT in THF at room temperature. The   Table I. The polymers were obtained in good yield as precipitated powders, which were not swollen in any solvents. Characterization of the insoluble network polymers is difficult, and we focused on the structure of the liner (branched) and/or low molecular weight fractions of the obtained polymers, which were soluble in some organic solvents. In this experiment, chloroform was selected as the solvent due to the high solubility of the polymer fractions. Figure 1a shows relationship between DEB feed ratio and wt% of chloroform soluble fraction of the resulting polymers. The chloroform soluble fraction increased with increasing the feed ratio of DEB. Increase of the DEB should increase the linearity of the resulting polymer, as shown in Scheme 3. Molecular weights of the chloroform soluble fractions were lower than 1000, indicating formation of network fragment. TEB-BDT/BT network polymers were also synthesized by the same way. The results are summarized in Table II. Figure 1b shows relationship between BT feed ratio and wt% of chloroform soluble fraction of the resulting polymers. The chloroform soluble fractions, whose molecular weights were less than 1000, increased with increasing the feed ratio of BT. Increase of the BT should increase fragmentation degree of the network polymer, as shown in Scheme 4. 1 H NMR spectrum of the chloroform soluble fraction of the polymer obtained in run 2 showed peaks at 7,2 6.2, and 3.6 ppm derived from phenyl group, unsaturated moiety, and thiol group, respectively. The chloroform solutions of other TEB/DEB-BDT network polymers and TEB-BDT/BT network polymers showed the similar peaks in their spectra.
Optical properties of the chloroform solutions of TEB/DEB-BDT and TEB-BDT/BT network polymers were investigated with UV-vis and PL spectroscopy. UV and PL spectra of TEB/DEB-BDT (run 5) and TEB-BDT/BT (run 9) network polymers are shown in Figures 2a  and 2b, respectively. The maximum absorption peaks (λ max ) in the UV spectroscopy and PL spectroscopy are summarized in Tables I  and II. The chloroform solutions of the network polymers showed UV spectra with an absorption peak at about 360 nm, which should be derived from π-π * transition. The wave length was blue shifted in comparison with that of the phenylene-vinylene based polymers. Existence of sulfide in the π-conjugation would cause the shift of the absorption peak. The wave length of the λ max increased with increasing of DEB feed ratio in the TEB/DEB-BDT network polymers. Increase of the DEB feed ratio would increase the linearity of the resulting polymer, which increased the wave length of λ max in the UV spectra. By contrast, the wave lengths of λ max of the TEB-BDT/BT network polymers were almost independent of the BT feed ratio, indicating degree of the fragmentation of the network would not affect the wave length of the UV spectra.   PL spectra of the chloroform soluble fraction of the network polymers were acquired exited at the λ max in the UV spectra. The fractions of TEB/DEB-BDT network polymers showed the peak (λ max ) at around 440-460 nm, which were larger than those of the TEB-BDT/BT network polymers, 410-430 nm. The difference in the λ max would be derived from linear π-conjugation length of the fractions.

BTT(-BDT, BPDT) network polymers.-BTT, BTT-BDT, and
BTT-BPDT network polymers were synthesized by the oxidation reaction in (with) DMSO at 50°C for 10 min. The network polymers were obtained quantitatively as white powders (Figure 4a). Figure 3 shows FT-IR spectra of BTT monomer and BTT network polymer. Intensity of the absorption peak at 2560 cm −1 derived from thiol group of BTT decreased, and the peak at 530 cm −1 derived from disulfide bond newly appeared in the spectrum of the BTT network polymer. These results indicate formation of network polymer by the disulfide bond derived from oxidation of thiol groups. The FT-IR spectroscopy of BTT-BDT and BTT-BPDT network polymers showed similar changes in the spectra. In the case of the reaction of non-aromatic thiol compounds, the reaction at 85°C for 8 h is necessary to obtain the network polymer. 5 The high reactivity of the aromatic thiol compounds should make it possible to obtain the network polymer under lower temperature and shorter reaction time.
The network polymers are stable against normal light or UV irradiation. Reductive degradation of the BTT network polymer was investigated by TCEP and DTT at room temperature. The degradation  with TCEP in the buffer turned to the solution for 24 h, as shown in Figure 4b, indicating degradation of the network polymer by reduction of disulfide bonds. By contrast, the network polymer in THF solution with DTT remained solid, as shown in Figure 4c. These results can be explained by low reduction ratio of the disulfide bonds in the network. In the case of the reduction with DTT, two types of DTT, oxidized and reduced DTT, would co-exist in the reaction system. The pK a value of the aromatic thiol BTT is 5.2, which is smaller than that of DTT, 14.5. The reduced BTT would be re-oxidized by oxidized DTT under the conditions, and the network structure should be remained in spite of the long reaction time. By contrast, TCEP did not play a role of the oxidant, and should promote reduction of the disulfide bonds in the network structure. The BTT-BDT, and BTT-BPDT network polymers were also completely degradable by TCEP.

Conclusions
The network polymers were successfully synthesized by noncatalytic thiol-yne reaction of multifunctional aromatic thiol compounds. The TEB/DEB-BDT and TEB-BDT/BT network polymers were obtained in good yields. The feed ratio of DEB or BT increased the chloroform solution of the network polymers, which showed optical properties derived from the π-conjugation in the network structure. Increase of the linearity of the network polymer, by increase of DEB feed ratio, increased the absorption and emission wave length in the chloroform soluble fraction of TEB/DEB-BDT network polymer. Oxidation of BTT in DMSO yielded the network polymer by formation of the disulfide bond. The network polymer was degradable by reduction with TCEP.
The multifunctional aromatic thiol compounds should be usable monomers to synthesize the network polymers using thiol-yne and oxidation reactions. Combination of functional monomers with the aromatic thiol compounds would make it possible to synthesize the network polymer with high performance. Addition of hydrophilicity to the network polymer with residual aromatic thiol groups would be applicable for medical use. For examples, visualization of biological redox reaction in the peptide and protein chemistries. We are planning to synthesize highly functionalized network polymers using thiol-yne reaction, and the results will be reported elsewhere.