Cyclic thioacetal carbonates for dual-stimuli degradable poly(vinyl ether)s with cleavable thioacetal and carbonate bonds evenly distributed in the main chains by cationic degenerative chain-transfer copolymerization

Abstract

We report the synthesis of dual-stimuli degradable poly(vinyl ether)s with cleavable thioacetal and carbonate bonds evenly distributed in the main chains using cationic degenerative chain-transfer (DT) copolymerization of vinyl ethers with macrocyclic thioacetal carbonates (CTAC). The 22- and 26-membered cyclic thioacetal carbonates (22-CTAC and 26-CTAC) were initially synthesized by a cationic thiol–ene reaction between divinyl ether with a carbonate bond and dithiol with or without a carbonate bond under dilution conditions. These compounds were subjected to cationic copolymerization with vinyl ethers using the HCl-adduct of isobutyl vinyl ether as an initiator and ZnCl₂ as a catalyst and were consumed much faster than the vinyl ethers by ring-opening reactions despite the large ring to introduce thioacetal and carbonate bonds in the main chains of the products. The in-chain thioacetal bonds subsequently served as dormant bonds for the cationic DT polymerization of vinyl ethers and enabled the synthesis of poly(vinyl ether)s with controlled total and segmental molecular weights between the thioacetal and carbonate bonds. The orthogonal degradations were successful when acid and base catalysts were used for the thioacetal and carbonate bonds, respectively; this resulted in low-molecular-weight products with controlled molecular weights. Furthermore, multiblock copolymers were synthesized by the one-time addition of the second monomer (B) to the cationic DT polymerization of the first monomer (A) and 22-CTAC and were selectively degraded into ABA and BAB triblock copolymers with acid and base catalysts, respectively.

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Introduction

The development of degradable polymer materials is urgently needed since the environmental issues caused by plastic waste have become more severe. In addition to microbial degradation in the natural environment, chemical degradation induced by external stimuli is also useful for developing sustainable polymer materials. Recently, interest in the synthesis of novel polymers with specific bonds that can be cleaved by chemical stimuli has increased.^1–5 These polymers can be chemically degraded and further recycled. Alternatively, chemically degraded low-molecular-weight products can undergo biodegradation naturally, although a rational design of the polymers is needed. Furthermore, more recently, multi-stimuli degradable polymers have attracted increased interest because of their ability to degrade in response to different conditions.^6–8

Among various synthetic polymers, vinyl polymers have the most significant challenges for degradation because their main chains are composed of stable carbon–carbon single bonds. Several strategies have been developed to increase the degradability or recyclability of vinyl polymers.^9–22 One effective direct approach is the use of heteroatom-containing cyclic monomers that can copolymerize with common vinyl monomers. These cyclic monomers can undergo ring-opening reactions to enable the incorporation of more cleavable carbon–heteroatom bonds in the main chain of the resulting copolymers.^23–51 Alternatively, recent publications have revealed that even acyclic compounds with heteroatoms can be used for the incorporation of heteroatoms in the main chains via copolymerization with vinyl monomers, as reported in the direct polymerization of carbon–heteroatom double bonds such as C=S and C=O in thiocarbonyl and carbonyl copmpounds^52–57 and isomerization radical polymerizations of specific vinyl ethers accompanying 1,5-shift of atoms and groups.^58–60 In these copolymerization approaches, however, the controlled incorporation of heteroatoms in the main chain is generally difficult except for alternating copolymerization because the comonomers are randomly copolymerized according to the monomer reactivity ratios. Controlled incorporation of carbon–heteroatom bonds is more desirable in terms of regulating the molecular weights of the degraded vinyl oligomer products; these degraded products may further undergo biodegradation.^61–63

One of the most useful methods to control the molecular weight of the vinyl polymers is “living”/controlled polymerization or reversible deactivation polymerization; here, the dormant polymer terminal functions as a reversibly cleavable bond during the polymerization to enable continuous controlled chain growth. However, dormant bonds are usually located at the polymer terminal. Recently, we developed controlled cationic polymerizations that proceeded via reversible activation of the C–S bond via degenerative chain transfer (DT) or reversible addition–fragmentation chain transfer (RAFT) of the cationic propagating species to the dormant thioester and thioacetal terminals.^64–80 We also found that thioacetal bonds could be constructed as main-chain linkages of polythioacetals via cationic thiol–ene polyaddition of dithiol and divinyl ethers^72,81 or cationic ring-opening polymerization of cyclic thioacetal (CTA).⁸⁰ These bonds could be used as in-chain dormant bonds for the subsequent cationic DT polymerization of vinyl ethers, resulting in copolymers with sulfur atoms in the main chain. In particular, a 7-membered cyclic thioacetal (7-CTA) efficiently undergoes cationic copolymerization with vinyl ethers through a ring-opening reaction. Here, 7-CTA is consumed much faster than vinyl ethers and is able to produce mostly polythioacetals in the initial stage. The resulting thioacetal bonds in the main chain serve as in-chain dormant species for the cationic DT polymerization of the remaining vinyl ethers. Thus, vinyl ethers are schematically inserted into the main-chain thioacetal bonds to form the copolymers, in which both the whole and segmental molecular weights of the poly(vinyl ether)s are controlled via the DT mechanism. Subsequent treatment of the resulting copolymers with silver nitrate or organic acid solution cleaves the main-chain thioacetals to finally result in poly(vinyl ethers)s with low and controlled molecular weights. Thus, the thioacetal bond in CTA has multiple functions, i.e., a polymerizable group of the cyclic monomer, an in-chain dormant bond for the cationic polymerization of vinyl ethers, and a degradable bond in the resulting vinyl polymers.

In this study, we investigated the synthesis of dual-stimuli degradable poly(vinyl ether)s via the incorporation of another degradable bond in CTA and subsequent cationic DT copolymerization with vinyl ethers (Scheme 1). Herein, in addition to the acid-cleavable thioacetal bond, carbonate was chosen as the other degradable bond, and could be cleaved under basic conditions, thus enabling dual-stimuli degradation. Novel macrocyclic thioacetals with carbonate bonds were synthesized by a cationic thiol–ene reaction between divinyl ether with a carbonate bond and dithiol with or without a carbonate bond under dilution conditions. The obtained macrocyclic thioacetal carbonate was used as a comonomer and a precursor for the in-chain dormant species in the cationic copolymerization with vinyl ethers. In this case, the carbonate bond could be introduced into the main chains along with the thioacetal bond via the ring-opening reaction of the macrocyclic thioacetal carbonate. The cationic DT polymerization of vinyl ethers based on the in-chain thioacetal bonds enabled the formation of poly(vinyl ether)s with controlled segment lengths, which were linked with both thioacetal and carbonate bonds. The orthogonal degradation of the obtained copolymers was investigated using acid and base catalysts for the cleavage of thioacetal and carbonate bonds, respectively. Furthermore, the one-pot synthesis of multiblock copolymers with dual degradability was also investigated.

Scheme 1 Synthesis and selective degradation of poly(vinyl ether)s with periodically distributed thioacetal and carbonate bonds in main chains by cationic degenerative chain-transfer copolymerization of vinyl ethers and cyclic thioacetal carbonate.

Results and discussion

Synthesis of macrocyclic thioacetal carbonate

Macrocyclic thioacetal carbonates were synthesized by a cationic thiol–ene reaction between a divinyl ether with a carbonate group and a dithiol with or without a carbonate group using benzenesulfonic acid (BSA) as an acid catalyst under dilution conditions (Scheme 2).⁸¹

Scheme 2 Synthesis of cyclic thioacetal carbonate by cationic thiol–ene reaction between divinyl ether with carbonate linkage and dithiol.

The synthesis of a 22-membered cyclic thioacetal carbonate (22-CTAC) with one carbonate and two thioacetal bonds is first described (Scheme S1†). A symmetrical divinyl ether with a carbonate group, i.e., bis[4-(vinyloxy)butyl]carbonate (DVE-1), was prepared by the reaction between 4-hydroxybutyl vinyl ether and 1,1′-carbonyldiimdazole. A dithiol, bis(2-mercaptoethyl)ether (DT-1), was commercially available. Then, the cationic thiol–ene reaction between DVE-1 and DT-1 was examined with equimolar amounts under dilution conditions ([DVE-1]₀/[DT-1]₀ = 25/25 mM) in the presence of a catalytic amount of BSA ([BSA]₀ = 0.10 mM) in CH₂Cl₂ at −40 °C. Both thiol and vinyl ether were quantitatively consumed. The peak-top molecular weight (M_p) of the size-exclusion chromatography (SEC) curve of the main product was 340; this result indicated the formation of a 1 : 1 adduct (Fig. 1A). After purification by silica column chromatography, the SEC curve became monomodal. In addition, the ¹H NMR spectrum showed characteristic peaks; these peaks were attributed to thioacetal (b) and carbonate (e) groups and were present at a 2 : 1 ratio (Fig. 1B). In addition, the MALDI-TOF-MS spectrum also confirmed that the main product was the desired 1 : 1 adduct (Fig. S3†). Thus, a 22-membered cyclic thioacetal carbonate (22-CTAC) with two thioacetal bonds and one carbonate bond was successfully synthesized.

Fig. 1 SEC curves (A and C) and ¹H NMR spectra (CDCl₃, r.t.) (B and D) of 22-CTAC (for A and B) and 26-CTAC (C and D) obtained by cationic thiol–ene reaction of DVE-1 and dithiols under dilute conditions: [DVE-1]₀/[DT-1]₀/[BSA]₀ = 25/25/0.10 mM or [DVE-1]₀/[DT-2]₀/[BSA]₀ = 50/50/0.20 mM in CH₂Cl₂ at −40 °C.

Another cyclic thioacetal carbonate (26-CTAC) with a 26-membered ring linked by two carbonate and two thioacetal bonds was also prepared by a similar cationic thiol–ene reaction involving an equimolar mixture of DVE-1 and bis(3-mecaptopropyl)carbonate (DT-2); DT-2 was prepared from bis(3-choloropropyl)carbonate and potassium thioacetate followed by deacetylation (Scheme S2†). In this case, both divinyl ether (DVE-1) and dithiol (DT-2) possess a carbonate bond. Although slightly higher amounts of high-molecular-weight products were observed in the SEC curve of the products, the main product with an M_p of 406 was purified by column chromatography (Fig. 1C). The ¹H NMR spectrum showed two kinds of carbonate peaks (e and h) and one thioacetal peak (b) with a peak area ratio of (e + h) : b = 4 : 1 (Fig. 1D); these results indicated that this molecule had two different carbonate bonds and two identical thioacetal bonds. The formation of macrocyclic 26-membered cyclic thioacetal carbonate was also supported by the MALDI-TOF-MS spectrum (Fig. S8†).

22-Membered cyclic thioacetal carbonate for cationic DT copolymerization with ethyl vinyl ether

Cationic copolymerization of ethyl vinyl ether (EVE) and 22-CTAC was investigated with the HCl adduct of isobutyl vinyl ether (1) as an initiator and ZnCl₂ as a catalyst in a similar way to the copolymerization of EVE and 7-CTA.⁸⁰ Fig. 2 shows representative results for the copolymerization in the mixture of CH₂Cl₂, toluene, and Et₂O (80/10/10) at −40 °C, where the feed ratios of the monomers (EVE + 22-CTAC) to the initiator (1) and EVE to 22-CTAC were 200 + 10 and 20, respectively ([EVE]₀/[22-CTAC]₀/[1]₀ = 4000/200/20 mM). The cyclic thioacetal carbonate was consumed more rapidly than EVE, irrespective of the large ring, and both monomers were quantitatively consumed (Fig. 2A). In the SEC curves, two peaks were present, and both shifted to the high-molecular-weight regions along with the consumption of EVE (Fig. 2B). As the polymerization proceeded, the lower-molecular-weight peak was attributed to the cyclic oligomers formed via the intramolecular DT reaction and decreased.⁸⁰ The number-average molecular weight (M_n) of the main peak linearly increased with monomer conversion and was in good agreement with the theoretical values, assuming that one copolymer chain was generated from one molecule of 1 (Fig. 2B). However, the dispersities (Đ) were relatively broad during the polymerization. This was attributed to the shuffling of poly(EVE) segments among the polymer chains because the growing carbocationic species could attack the in-chain dormant thioacetal bonds to induce reversible main-chain cleavage via the DT mechanism. These results were similar to those obtained with 7-CTA, as reported previously.⁸⁰ Thus, despite the larger ring size, the 22-membered macrocyclic thioacetal carbonate, i.e., 22-CTAC, successfully underwent cationic DT copolymerization with EVE.

Fig. 2 Time-conversion curve (A), M_n values (B), and SEC curves (C) of the polymers obtained in cationic DT copolymerization of EVE and 22-CTAC: [EVE]₀/[22-CTAC]₀/[1]₀/[ZnCl₂]₀ = 4000/200/20/4.0 mM in CH₂Cl₂/n-hexane/Et₂O (20/10/10) at −40 °C.

Then, the final product was purified to remove the lower-molecular-weight oligomers using preparative SEC to produce the isolated main product (M_n = 17 900, Đ = 2.20), and this product was then analyzed by ¹H NMR spectroscopy. The characteristic peaks derived from the ring-opened structure of 22-CTAC were the methine proton of the thioacetal at 4.7 ppm (e), the methylene proton next to the sulfur atom at 2.7 ppm (f), and the methylene proton (l) next to the carbonate group at 4.1 ppm; these peaks were observed in addition to the large peaks of the poly(EVE) segments (Fig. 3A). These results indicated that the thioacetal and carbonate bonds derived from 22-CTAC were incorporated into the poly(EVE) main chains via a ring-opening reaction.

Fig. 3 ¹H NMR spectra (CDCl₃, 55 °C) of the obtained copolymer of EVE and 22-CTAC (A) and the polymers after degradation using an AgNO₃ solution (B) and using a NaOCH₃ solution (C): [thioacetal unit]₀/[AgNO₃]₀ = 5.0/50 mM in THF/H₂O at 20 °C or [carbonate unit]₀/[NaOCH₃]₀ = 5.0/50 mM in CH₃OH at 60 °C. *: H₂O, ‡: CHCl₃.

Furthermore, additional small peaks were present and attributed to the terminal protons, such as the methyl proton (α₂) of the isobutyl group at the α-chain end derived from the initiator at 0.9 ppm and the methine proton (ω₁) of the acetal at the ω-chain end generated via termination reaction with methanol at 4.6 ppm; this peak overlapped with the methine proton of the main-chain thioacetal (e). The average number (2m) of the incorporated thioacetal bonds calculated from the integral ratio of f to α₂ was 18. Additionally, the average number (m) of the incorporated carbonate bonds calculated from the integral ratio of l to α₂ was 9; this value was in agreement with half the number of thioacetal bonds. These numbers were close to the theoretical values calculated from the feed ratio of 22-CTAC to 1 ([22-CTAC]₀/[1]₀ = 10); these results indicated that 22-CTAC was quantitatively incorporated into the polymer main chains. Moreover, the number-average degree (n) of poly(EVE) segments per thioacetal bond was calculated from the integral ratio of EVE units to the sum of in-chain thioacetal and terminal acetal bonds and was determined to be 10. These results indicated that the obtained copolymer was composed of 19 (= 2m + 1) poly(EVE) segments with 10 (= n) EVE units on average and contained 18 (= 2m) thioacetal bonds and 9 (= m) carbonate bonds in the main chain.

Degradation of the copolymer

The thioacetal and carbonate bonds in the polymer main chains could be selectively cleaved by different stimuli or catalysts. The selective degradation of the obtained copolymers was investigated using different catalysts. The degradation via hydrolysis of the thioacetal bonds was initially examined using an AgNO₃ solution in a mixture of THF and H₂O at room temperature.^80,82–85 After 3 h, the SEC curve of the products shifted to the low-molecular-weight region (Fig. 4A). The M_n value decreased to 2200 and was in agreement with the calculated value (2000), assuming that one thioacetal bond formed one poly(EVE) segment. In addition, the dispersity of the degraded products decreased (Đ = 1.27). The ¹H NMR spectrum of the resulting products revealed that the peak (e) derived from the thioacetal bond at 4.6 ppm completely disappeared and that a new peak (x) attributed to the aldehyde terminal was formed via hydrolysis and appeared at 9.8 ppm (Fig. 3B). Furthermore, the peaks derived from carbonate bonds remained unchanged after treatment with the AgNO₃ solution. These results indicated that the thioacetal bonds were evenly distributed in the main chain of the obtained copolymers and that they were selectively cleaved by AgNO₃. A similar selective cleavage of the thioacetal bonds was also examined using a common organic acid such as p-toluenesulfonic acid. The degradation was slower, but the selective degradation was supported by the SEC and ¹H NMR analyses (Fig. S9 and S10†).

Fig. 4 SEC curves of the products before and after degradation with AgNO₃ (A) and NaOCH₃ (B), and SEC curves of the products obtained by dual degradation with the sequential use of NaOCH₃ and AgNO₃ (C): [thioacetal unit]₀/[AgNO₃]₀ = 5.0/50 mM in THF/H₂O at 20 °C. [Carbonate]₀/[NaOCH₃]₀ = 5.0/50 mM in CH₃OH at 60 °C.

The selective degradation of the carbonate bonds was then investigated via methanolysis using a NaOCH₃ solution in CH₃OH at 60 °C. The SEC curve of the products obtained after 48 h shifted to the low-molecular-weight region (M_n = 2500) and became narrow (Đ = 1.23) (Fig. 4B), as in the case of AgNO₃. More interestingly, peak (l) of the methylene proton adjacent to the carbonate groups completely disappeared, whereas peak (e) attributed to the thioacetal bonds remained intact (Fig. 3C). These results indicated that selective complementary degradation occurred when the base catalyst was used in place of the acid catalyst. The degradations were thus orthogonal. Additionally, kinetic comparison under these specific conditions revealed that degradation of carbonate bonds with NaOCH₃ proceeded much slower than that of thioacetal bonds with AgNO₃. The degradation progress with NaOCH₃ was examined by SEC and ¹H NMR (Fig. S11 and S12†). As shown in Fig. S12,† the M_n values of the products were measured by SEC and decreased with increasing degradation of the carbonate moiety, as measured by ¹H NMR (Fig. S11†). The plots were effectively fit with the theoretical curves, assuming that the carbonate bonds were evenly incorporated into the main chains of the copolymers.

Based on these results, stepwise degradation was investigated using a base catalyst followed by an acid catalyst. The first degradation using the NaOCH₃ solution resulted in a low-molecular-weight polymer with a narrow dispersity (M_n = 2600, Đ = 1.24) (Fig. 4C). The recovered polymer with thioacetal bonds was subsequently subjected to a second degradation using the AgNO₃ solution. The SEC curve further shifted to the low-molecular-weight region; this resulted in a product with M_n = 1400, which was reduced by approximately half of the first degraded products. These results indicated that the thioacetal bonds were located around the middle of the first degradation products and that dual-stimuli degradable poly(EVE) with thioacetal and carbonate bonds, which were evenly distributed in the main chain, was obtained by the cationic DT copolymerization of EVE and 22-CTAC.

Tunable molecular weights before and after degradation

In this copolymerization, the overall molecular weights of the products before degradation could be controlled by the feed ratio of total monomers to initiator, whereas the molecular weights of the degraded products could be controlled by the feed ratio of vinyl ether to cyclic thioacetal.⁸⁰

Here, the control of the total molecular weight of the copolymer was investigated by changing the feed ratio of the total monomers to the initiator (([EVE]₀ + [22-CTAC]₀)/[1]₀ = 100 + 5, 200 + 10, and 400 + 20), while the feed ratio of vinyl ether to cyclic thioacetal carbonate was fixed ([EVE]₀/[22-CTAC]₀ = 20). This enabled the synthesis of polymers with different overall molecular weights while maintaining the same molecular weights of the degraded products. In all cases, 22-CTAC was consumed much faster than EVE (Fig. S13†), resulting in copolymers (Fig. S14†). The M_n values of the products varied with the feed ratio of total monomers to initiator (M_n = 10 000–40 000) and effectively agreed with the theoretical values, assuming that one initiator generates one polymer chain (Fig. 5A).

Fig. 5 Effect of varying ([EVE]₀ + [22-CTAC]₀)/[1]₀ with constant [EVE]₀/[22-CTAC]₀ on M_n values (A) and SEC curves (B and C) of the polymers obtained by cationic DT copolymerizations of EVE and 22-CTAC before and after degradation: [EVE]₀/[22-CTAC]₀/[1]₀/[ZnCl₂]₀ = 4000/200/10, 20, 40/4.0 mM in CH₂Cl₂/n-hexane/Et₂O (20/10/10) at −40 °C. [Thioacetal unit]₀/[AgNO₃]₀ = 5.0/50 mM in THF/H₂O at 20 °C. [Carbonate]₀/[NaOCH₃]₀ = 5.0/50 mM in CH₃OH at 60 °C.

The selective degradation of a series of copolymers with different total molecular weights was examined similarly using AgNO₃ and NaOCH₃ solutions. In all cases, the SEC curves shifted to the low-molecular-weight region and became narrower (Đ = 1.2–1.3) (Fig. 5B and C). Despite the different original molecular weights and different stimuli used, the M_p and M_n after degradation were nearly the same (M_n ∼ 2000) and agreed well with theoretical values. Thus, this method enabled the synthesis of a series of dual-stimuli degradable polymers; these polymers had overall different molecular weights tunable by the varied feed ratios of monomers and initiators but could be degraded into the same molecular weights determined by the fixed feed ratio of vinyl ether to cyclic thioacetal carbonate.

Next, the control of the molecular weights of the degraded products was examined by varying the concentration of cyclic thioacetal carbonate without changing the concentrations of the vinyl ether and initiator. The feed ratio of EVE to 22-CTAC was varied from 10 to 20 and 40 ([EVE]₀/[22-CTAC]₀ = 10, 20, and 40), whereas that of EVE to 1 was kept constant at 200 ([EVE]₀/[1]₀ = 200). The consumption of 22-CTAC was much faster than that of EVE in all cases (Fig. S15†), resulting in copolymers (Fig. S16†). The SEC analysis of the products revealed that the molecular weights of the obtained copolymers were nearly constant (M_n ∼ 20 000) (Fig. 6A).

Fig. 6 Effect of varying [EVE]₀/[22-CTAC]₀ with constant [EVE]₀/[1]₀ on M_n values and SEC curves (B and C) of the polymers obtained by cationic DT copolymerizations of EVE and 22-CTAC before and after degradation: [EVE]₀/[22-CTAC]₀/[1]₀/[ZnCl₂]₀ = 4000/100, 200, 400/20/4.0 mM in CH₂Cl₂/n-hexane/Et₂O (20/10/10) at −40 °C. [Thioacetal unit]₀/[AgNO₃]₀ = 5.0/50 mM in THF/H₂O at 20 °C. [Carbonate]₀/[NaOCH₃]₀ = 5.0/50 mM in CH₃OH at 60 °C.

AgNO₃ and NaOCH₃ were then similarly used for selective degradation. All SEC curves of the degraded products shifted to low-molecular-weight regions with decreasing dispersity (Fig. 6B and C). Here, the shifts became more remarkable as the 22-CTAC feed increased, and they were nearly independent of the catalysts (AgNO₃ and NaOCH₃) used for degradation. Furthermore, the M_n values of the degraded products were close to the theoretical values in which one thioacetal bond generated one poly(EVE) segment and linearly increased with the feed ratio of EVE to 22-CTAC. Thus, another series of dual-stimuli degradable polymers, with the same molecular weights determined by the fixed feed ratio of vinyl ether to initiator, could be degraded into different molecular weights that were tunable by the varied feed ratios of vinyl ether to cyclic thioacetal carbonate.

These results indicated that dual-stimuli degradable polymers with tunable molecular weights before and after degradation could be synthesized by cationic DT copolymerization of vinyl ether and macrocyclic thioacetal carbonate, which has two thioacetal bonds and one carbonate bond.

Effect of cyclic thioacetal carbonate: 26-CTAC vs. 22-CTAC

The other macrocyclic thioacetal carbonate (26-CTAC) with two carbonate and two thioacetal bonds in a larger ring was similarly copolymerized with EVE to synthesize another series of dual-stimuli degradable poly(EVE). In contrast to 22-CTAC, 26-CTAC possesses another carbonate bond originating from the dithiol unit (DT-2) as the starting material in addition to the other carbonate bond originating from the divinyl ether unit (DVE-1). Consequently, the base-induced degradation of the polymers produced from 26-CTAC could reduce the molecular weight of the degraded products to half of that of those from 22-CTAC.

The cationic DT copolymerization of 26-CTAC and EVE was similarly examined using the 1/ZnCl₂ system. The consumption of 26-CTAC occurred more rapidly than that of EVE (Fig. 7A), as in the case of 22-CTAC. The SEC curves shifted to high-molecular-weight regions as the polymerization proceeded (Fig. 7B). The M_n of the main peak increased in direct proportion to monomer conversion and was similar to the calculated value (Fig. S17†). The ¹H NMR spectrum of the main-peak products purified by preparative SEC revealed two kinds of carbonate bonds and one kind of thioacetal bond originating from 26-CTAC (Fig. S18A†). The average numbers of the incorporated thioacetal bonds (2m) and carbonate bonds (2m) calculated from the respective peak area ratios were both 16. The number-average degree (n) of poly(EVE) segments per thioacetal or carbonate bond was 10 (Fig. S18A†). These values were similar to the theoretical values determined by the feed ratios. Thus, 26-CTAC similarly underwent cationic ring-opening copolymerization with EVE to produce polymers with twice the number of carbonate bonds in the polymer chains as those obtained with 22-CTAC.

Fig. 7 Time-conversion curve (A) and SEC curves of the polymers obtained in cationic DT copolymerization of EVE with 26-CTAC before (B) and after (C) degradation with AgNO₃ and NaOCH₃: [EVE]₀/[26-CTAC]₀/[1]₀/[ZnCl₂]₀ = 4000/200/20/8.0 mM in CH₂Cl₂/n-hexane/Et₂O (20/10/10) at −40 °C. [Thioacetal unit]₀/[AgNO₃]₀ = 5.0/50 mM in THF/H₂O at 20 °C. [Carbonate]₀/[NaOCH₃]₀ = 5.0/50 mM in CH₃OH at 60 °C.

The selective degradation of the thioacetal and carbonate bonds was then investigated using AgNO₃ and NaOCH₃ solutions, respectively. In both cases, the SEC curves of the products shifted to the low-molecular-weight region and became narrower (Fig. 7C). In particular, the M_n value after degradation with NaOCH₃ was reduced to approximately half of that obtained with AgNO₃. This result was consistent with the designed polymer structure and indicated that the dual-stimuli degradable poly(vinyl ether)s were rationally designed on the basis of the structure of the macrocyclic thioacetal carbonates.

Various vinyl ethers for cationic copolymerization with 22-CTAC

To adapt the dual-stimuli degradable poly(vinyl ether)s, other vinyl ethers, such as isobutyl (IBVE) and 2-methoxyethyl vinyl ether (MOVE), which are typical hydrophobic and hydrophilic monomers widely used in cationic polymerizations, were copolymerized with 22-CTAC. As in the case of EVE, IBVE and MOVE were nearly quantitatively consumed after rapid consumption of 22-CTAC (Fig. 8). In both cases, the M_n values of the obtained copolymers increased in direct proportion to monomer conversion and were similar to the theoretical values (Fig. S20 and S21†). The M_n of the final products reached 20 000 in this case.

Fig. 8 Cationic DT copolymerization of IBVE (A) and MOVE (B) with 22-CTAC and SEC curves before and after stepwise degradation: [VE]₀/[22-CTAC]₀/[1]₀/[ZnCl₂]₀ = 4000/200/20/4.0 mM in CH₂Cl₂/n-hexane/Et₂O (20/10/10) at −40 °C. [Thioacetal unit]₀/[AgNO₃]₀ = 5.0/50 mM in THF/H₂O at 20 °C. [Carbonate]₀/[NaOCH₃]₀ = 5.0/50 mM in CH₃OH at 60 °C.

The obtained copolymers were also analyzed by ¹H NMR. The broad large peaks were attributed to each vinyl ether unit and relatively sharp peaks derived from the ring-opened 22-CTAC units (Fig. S22 and S23†). The average numbers of thioacetal (2m) and carbonate bonds (m) in each copolymer were 18 and 9 for IBVE and 20 and 10 for MOVE, respectively. In addition, the number-average degrees (n) of the poly(IBVE) and poly(MOVE) segments were 10 and 14, respectively, and were similar to the theoretical values based on the feed ratio of the monomers to the initiator. Thus, these vinyl ethers were also successfully copolymerized with 22-CTAC.

The obtained copolymers were then subjected to stepwise degradation using NaOCH₃ and AgNO₃ sequentially. In both cases, the first reaction with NaOCH₃ significantly shifted the SEC curves to low-molecular-weight regions, where the M_n values of the products decreased to approximately 2000 and became narrower (Fig. 8). The second reaction with AgNO₃ resulted in M_n values approximately half those of the first products. Thus, cyclic thioacetal carbonates could be widely used for the synthesis of various dual-stimuli degradable poly(vinyl ether)s with different side chains.

Multiblock copolymers with dual-stimuli degradability

Finally, the one-pot synthesis of dual-stimuli degradable multiblock poly(vinyl ether)s was investigated via the only one-time addition of a second monomer (B) to the copolymerization of the first vinyl ether (A) and 22-CTAC. Herein, the main-chain thioacetal bond formed in the first copolymerization works as the in-chain dormant bond, into which the second monomer was schematically inserted to form the AB diblock copolymer segments connected by both thioacetal and carbonate bonds. Moreover, as shown in the scheme in Fig. 9, the carbonate bond should be located in the middle of the first segment (poly(A)), whereas the two thioacetal bonds should be located in the middle of the second segment (poly(B)). The selective degradation of the copolymers using AgNO₃ and NaOCH₃ should result in different triblock copolymers, i.e., ABA and BAB copolymers, respectively.

Fig. 9 One-pot synthesis of dual-degradable multiblock copolymers linked by thioacetal bonds and degradation with AgNO₃ (A) and NaOCH₃ (B) into the triblock copolymers: [IBVE]₀/[EVE]_add/[22-CTA]₀/[1]₀/[ZnCl₂]₀ = 2000/2000/200/20/4.0 mM in CH₂Cl₂/n-hexane/Et₂O (20/10/10) at −40 °C. [Thioacetal unit]₀/[AgNO₃]₀ = 5.0/50 mM in THF/H₂O at 20 °C. [Carbonate]₀/[NaOCH₃]₀ = 5.0/50 mM in CH₃OH at 60 °C.

To demonstrate this feasibility, IBVE was chosen as the first monomer (A) and copolymerized with 22-CTAC using the 1/ZnCl₂ initiating system. After quantitative consumption of IBVE, EVE was added to the reaction solution as the second monomer (B) and was also smoothly consumed (Fig. S26†). After the addition of EVE, the SEC curves (black solid lines in Fig. 9) shifted to the high-molecular-weight regions; these results indicated that EVE was copolymerized into the main-chain thioacetal of the poly(IBVE) segments to form the block copolymer segments. The ¹H NMR analysis further supported the formation of block copolymers since the peaks attributed to both EVE and IBVE units were observed in addition to the peaks derived from the ring-opened 22-CTAC unit (Fig. S27†). The number-average degrees of poly(IBVE) and poly(EVE) segments were calculated from the integral ratios of each peak and were both 8, and the average number of thioacetal groups (2m) in the main chain was 11. These results showed the formation of the multiblock copolymer, in which 11 block copolymer segments with 8 IBVE and EVE units on average were connected with thioacetal and carbonate bonds.

The selective degradations of the first polymer and the multiblock copolymer were also investigated using AgNO₃ and NaOCH₃ separately. In the case of AgNO₃, both SEC curves of the products shifted to low-molecular-weight regions (green dashed lines) and became narrower (Fig. 9A). In particular, the SEC curve obtained from the multiblock copolymer was located in higher-molecular-weight regions than that obtained from the first polymer. Similar results were obtained for NaOCH₃ (orange dashed lines). Furthermore, the M_n values of the degraded products were independent of the catalyst. The ¹H NMR analysis also supported the selective degradation reactions. The peak derived from the thioacetal groups disappeared with AgNO₃ along with the appearance of aldehyde terminals, whereas the peak of the methylene protons adjacent to the carbonate group disappeared with NaOCH₃ (Fig. S28†). In contrast, the carbonate and thioacetal groups remained unchanged with AgNO₃ and NaOCH₃, respectively. Thus, the products degraded with AgNO₃ were ABA triblock polymers with carbonate bonds in the middle of the B-segment, whereas those obtained with NaOCH₃ were BAB triblock polymers with thioacetal bonds in the middle of the A-segment. These results indicated that the block copolymerization of different vinyl ethers using macrocyclic thioacetal carbonate enabled the one-pot synthesis of dual-degradable multiblock copolymers; ultimately, this resulted in the ABA and BAB triblock polymers by the selective orthogonal degradation.

Conclusions

The synthesis of dual-stimuli degradable poly(vinyl ether)s with thioacetal and carbonate bonds evenly distributed in the main chain was achieved by cationic DT copolymerization of vinyl ethers and the design of macrocyclic thioacetal carbonates; these were prepared by a cationic thiol–ene reaction between divinyl ether and dithiol containing carbonate bonds. The macrocyclic thioacetal carbonates underwent efficient ring-opening cationic polymerization to generate the main-chain thioacetal and carbonate bonds; here, the macrocyclic thioacetal carbonate served as dormant species for the cationic DT polymerization of the vinyl ethers to control the total and segmental molecular weights. The main-chain thioacetal and carbonate bonds were selectively degraded to low-molecular-weight products with narrow dispersities using acid and base catalysts, respectively. Furthermore, multiblock copolymers with dual degradability were synthesized by the one-time addition of the second monomer and were degraded into ABA and BAB triblock copolymers with different sequences by the orthogonal degradation. Furthermore, the carbonate bonds in macrocyclic thioacetal carbonate could be replaced with other cleavable bonds; this aspect will advance multi-degradable polymers and further contribute to the macromolecular design of sustainable polymer materials.

Author contributions

M. U., K. M., and M. K. designed the experiments. M. U. and K. M. conducted the experiments. M. U., K. M., and M. K. anaylzed the results. M. U. and M. K. prepared the manuscript.

Data availability

The data supporting this article have been included as part of the ESI.†

Conflicts of interest

There are no conflicts to declare.

Acknowledgements

This work was supported by a JSPS KAKENHI Grant-in-Aid for Scientific Research (C) (no. JP22K05209) for M. U. and for Scientific Research (A) (no. JP22H00333 and JP25H00894) for M. K., a JST CREST (no. JPMJCR22L2) for M. U., and a project (JPNP18016) commissioned by the New Energy and Industrial Technology Development Organization (NEDO). The authors would like to thank Hironobu Watanabe and Chihiro Homma for fruitful discussions and valuable comments on this research.

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Footnote

† Electronic supplementary information (ESI) available: Detailed information on materials, measurements, polymerization and degradation procedures, and additional polymer characterization data (SEC and NMR). See DOI: https://doi.org/10.1039/d5py00054h

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