A method for preparing a low-residual monomer styrene-maleic anhydride copolymer resin

Abstract

This invention discloses a method for preparing a low-residue styrene-maleic anhydride copolymer resin, belonging to the field of polymer synthesis technology. The preparation method includes: dissolving styrene monomer, maleic anhydride monomer, and a bifunctional trithiocarbonate RAFT reagent in an organic solvent, and then performing RAFT controlled free radical polymerization via thermal or photoinitiation. The R group of the RAFT reagent contains a 4-dimethylaminopyridine structure, which directionally enriches maleic anhydride monomer around the polymerization active center through dynamic hydrogen bonding-ion pairing, forcibly forming an alternating copolymer structure; its Z group contains a substituted cyclohexyl peroxyketal structure, which can decompose in situ under thermal or photo-triggered conditions to generate initiating free radicals without the need for an external initiator. This method achieves precise control of the copolymer's molecular weight and sequence structure, resulting in a resin with low free reagent and monomer residues, controllable number-average molecular weight, and a small molecular weight distribution coefficient.

Description

Technical Field

[0001] This invention relates to the field of polymer synthesis technology, and in particular to a method for preparing a low-residue monomer styrene-maleic anhydride copolymer resin. Background Technology

[0002] Styrene-maleic anhydride copolymer (SMA) resin is an important class of functional polymer materials. Due to its excellent film-forming properties, biocompatibility, and ability to interact with lipid bilayers to form nanoparticles, it has broad application prospects in biomedicine, separation membranes, and nanomaterial preparation. However, the traditional free radical polymerization method for preparing SMA has problems such as wide molecular weight distribution, high monomer residue, and difficulty in precisely controlling the copolymer composition. In particular, it is difficult to obtain copolymer products with strictly alternating structures and low residue.

[0003] In recent years, reversible addition-fragmentation chain transfer (RAFT) controlled radical polymerization has provided a new route for the precise synthesis of SMA. However, existing RAFT systems still face challenges: on the one hand, the large polarity difference between styrene and maleic anhydride monomers makes phase separation or compositional drift prone to occur during polymerization, resulting in heterogeneous product structures; on the other hand, traditional RAFT polymerization requires the addition of azo thermal initiators, and initiator fragments are difficult to completely remove. The resulting products require cumbersome purification steps such as dialysis or column chromatography, which limits their high-end applications in the biopharmaceutical field.

[0004] To address the aforementioned technical bottlenecks, a method for preparing SMA resin that requires no external initiator and can simultaneously achieve alternating structural regulation and low residual properties is developed. This method has significant technical value for improving material performance, simplifying the preparation process, and expanding application areas. Summary of the Invention

[0005] The purpose of this invention is to address the shortcomings of existing technologies by proposing a method for preparing a low-residual monomer styrene-maleic anhydride copolymer resin.

[0006] To achieve the above objectives, the present invention adopts the following technical solution:

[0007] This invention first proposes a method for preparing a low-residue styrene-maleic anhydride copolymer resin, comprising the following steps:

[0008] A homogeneous polymerization system was prepared by dissolving styrene (S) monomer, maleic anhydride (MAH) monomer, and difunctional trithiocarbonate RAFT reagent in an organic solvent.

[0009] RAFT controlled free radical polymerization reaction is carried out under inert gas protection via thermal initiation or photoinitiation.

[0010] After the reaction was completed, styrene-maleic anhydride copolymer resin was obtained through precipitation, solid-liquid separation, and drying.

[0011] In traditional systems, the polymerization rates of S and MA differ greatly, with S polymerization rate much faster than MA, which easily leads to problems such as compositional drift, low MA conversion, and homopolymerization of S. In this stage, local enrichment is used to increase the local concentration of MA around the active center by 4-6 times, which greatly reduces the difference in polymerization rates between S and MA, achieves synchronous copolymerization of the two monomers, reduces compositional drift, and lays the foundation for high conversion and low monomer residue in the future.

[0012] The bifunctional trithiocarbonate RAFT reagent is a compound having the structure shown in formula (Ⅰ):

[0013] (I) Equation;

[0014] In formula (I), the R group is connected to the thiocarbonyl carbon atom of the trithiocarbonate core through a monosulfide bond (-S-), and the Z group is connected to the thiocarbonyl carbon atom of the trithiocarbonate core through a monosulfide bond (-S-). The R group is a maleic anhydride monomer anchoring unit containing a 4-dimethylaminopyridine-propoxy structure, which can directionally enrich maleic anhydride monomers around the polymerization active center. The Z group is a dual-response in-situ initiation unit containing a substituted cyclohexyl peroxy ketal structure, which can generate initiating free radicals through thermal or phototriggered decomposition to achieve in-situ initiation of the polymerization reaction. The free radicals generated by the decomposition of the RAFT reagent are covalently connected to the Z end of the trithiocarbonate structure.

[0015] The pyridine ring tertiary amine group carries a positive charge and can form a dynamic hydrogen bond-ion pair with the carboxyl group of MA; at the same time, it is a good free radical leaving group, which can stabilize free radicals and re-initiate monomer polymerization; throughout the polymerization cycle, MA monomers are directionally enriched around the active center of the growing chain, solving the core pain point of mismatch between S and MA polymerization rates; as a RAFT leaving group, each polymer chain end carries an anchoring function.

[0016] The peroxide bond can undergo homolytic cleavage under thermal triggering at 70℃ and ultraviolet light triggering at 365nm, generating initiating free radicals; it does not undergo the leaving reaction in the RAFT process, and is covalently linked to the trithiocarbonate core throughout the process; it does not require an exogenous initiator, generates initiating free radicals in situ, and the free radicals are covalently linked to the RAFT reagent throughout the process, with no free small molecules generated, thus eliminating initiator residues;

[0017] The thiocarbonyl group is a reversible addition site for free radicals. Through a reversible addition-fragmentation chain transfer reaction, it enables rapid and reversible exchange of active species of free radicals and inhibits irreversible bimolecular termination. This allows for precise control of molecular weight and narrow molecular weight distribution in S-MA copolymerization, ensuring uniform copolymer composition and significantly reducing compositional drift.

[0018] Preferably, in formula (I), the 4-dimethylaminopyridine-propoxy structure of the R group is linked to the alkyl carboxyl group at the R end of the trithiocarbonate via an ester bond to form a dimethylaminopyridine structure, and the tertiary amine group contained therein can form a dynamic hydrogen bond-ion pair with the carboxyl group of the maleic anhydride monomer.

[0019] The substituted cyclohexyl peroxy ketal structure of the Z group is linked to the alkyl group at the Z end of the trithiocarbonate via an acetal bond. Its decomposition half-life in a 1,4-dioxane solvent at 70°C is 3.1 h, and it can decompose at room temperature under 365 nm ultraviolet light irradiation, achieving controllable initiation in both photo / thermal response.

[0020] Preferably, the preparation method of the bifunctional trithiocarbonate RAFT reagent includes the following steps:

[0021] S1. Synthesis of bifunctional intermediate: Using 2-mercaptoethanol and carbon disulfide as raw materials, xanthate is generated by reaction under alkaline ice bath conditions, and then reacted with 2-bromoisobutyric acid. After purification, intermediate 1 with a hydroxyl group at one end and a carboxyl group at the other end is obtained.

[0022] The molar ratio of 2-mercaptoethanol, carbon disulfide, and 2-bromoisobutyric acid is 1:1.2:1.

[0023]

[0024] Under alkaline ice bath conditions, the mercapto anion of 2-mercaptoethanol attacks carbon disulfide to form xanthate. Through nucleophilic substitution (SN2), the sulfur atom of xanthate attacks the α-carbon of 2-bromoisobutyric acid to form a trithiocarbonate bond.

[0025] The core framework of the RAFT reagent was constructed, with the central carbon-sulfur double bond (C=S) serving as the key active site for reversible addition-fragmentation chain transfer in RAFT polymerization. The hydroxyl and carboxyl groups at both ends provide functional groups for subsequent "orthogonal modification".

[0026] S2, R-terminal functionalization modification: 4-Dimethylaminopyridine is reacted with 3-bromo-1-propanol to obtain a 4-dimethylaminopyridine-propoxy anchoring unit with a terminal hydroxyl group, which is then esterified with the carboxyl group of intermediate 1, and purified to obtain R-terminal functionalized intermediate 2.

[0027] The molar ratio of 4-dimethylaminopyridine to 3-bromo-1-propanol is 1:1.2; the molar ratio of 4-dimethylaminopyridine-propoxy anchoring unit to intermediate 1 is 1:1.1.

[0028]

[0029] The pyridine nitrogen atom of 4-dimethylaminopyridine undergoes a quaternization reaction with 3-bromo-1-propanol to obtain a DMAP derivative with a terminal hydroxyl group. The carboxyl group of intermediate 1 is activated using a dehydrating agent and then undergoes esterification condensation with the hydroxyl group of the anchoring unit.

[0030] S3. Synthesis of target reagent: Cyclohexanone was reacted with tert-butyl hydrogen peroxide under acidic conditions to obtain a substituted cyclohexyl peroxy ketal initiating unit with a terminal hydroxyl group. This unit was then reacted with the terminal hydroxyl group of intermediate 2 to form an acetal. After purification, the bifunctional trithiocarbonate RAFT reagent was obtained.

[0031] The molar ratio of cyclohexanone to tert-butyl hydroperoxide is 1:2-5; the molar ratio of substituted cyclohexyl peroxy ketal initiating unit to intermediate 2 is 1.2:1.

[0032]

[0033] Under acidic catalysts, the carbonyl group of cyclohexanone undergoes condensation with tert-butyl hydroperoxide to form a ketal structure containing a peroxy bond (-OO-), and a terminal hydroxyl group is introduced for attachment.

[0034]

[0035] Under acid catalysis and dehydration conditions, the hydroxyl group at the end of intermediate 2 condenses with the hydroxyl group of the initiating unit to form an acetal bond (COC).

[0036] Preferably, the molar ratio of styrene monomer to maleic anhydride monomer is 1-3:1, the molar ratio of the bifunctional trithiocarbonate RAFT reagent to styrene monomer is 1:50-200, the organic solvent is 1,4-dioxane, and the total monomer mass concentration of the polymerization system is 20-40 w / v.

[0037] Preferably, the polymerization reaction temperature of the thermal initiation method is 60-80℃, and the reaction time is 20-40h.

[0038] Preferably, the photoinitiation method uses continuous irradiation with 365nm ultraviolet light, the polymerization reaction temperature is 20-30℃, and the reaction time is 2-6h.

[0039] Preferably, the precipitation step uses a 1 mol / L hydrochloric acid aqueous solution as the precipitant, and the drying step is vacuum freeze drying or vacuum drying at 40-60℃; the resulting styrene-maleic anhydride copolymer resin does not require dialysis or column chromatography purification, the free reagent-related residue is less than 1 ppm, and the residual monomer content is less than 0.1 wt%.

[0040] Preferably, the number-average molecular weight of the obtained styrene-maleic anhydride copolymer resin is 4000-10000 g / mol, and the molecular weight distribution coefficient is ≤1.35.

[0041] Preferably, the distribution of SSS, SSM / MSS, and MSM ternary components of the obtained styrene-maleic anhydride copolymer resin can be directionally controlled by the monomer feed ratio, and when it interacts with the lipid bilayer, it can form styrene-maleic anhydride lipid particles with a particle size of 6-9 nm.

[0042] Under heating (60-80℃) or ultraviolet light (365nm) irradiation, the Z-terminal peroxy bond (-OO-) undergoes homolytic cleavage, generating two alkoxy radicals.

[0043] Since the peroxy ketal structure is covalently linked to the Z-terminus, the free radical RO• generated after its breakage is covalently linked to the Z-terminus of the trithiocarbonate. When the free radical generated at the Z-terminus initiates chain growth of styrene or maleic anhydride monomers, the core trithiocarbonate (C=S) intervenes to regulate it.

[0044] The growing active polymer chain (Pn•) attacks the C=S double bond of the trithiocarbonate, forming an intermediate free radical. This intermediate free radical rapidly breaks, releasing the original R-terminal group (Z-terminal departure). More precisely, because the Z-terminus is connected to the initiating unit, the system is in a rapid equilibrium between "dormant" and "active" species. The vast majority of polymer chains exist in the "dormant" (trithiocarbonate-terminated) form, remaining active only a very few times.

[0045]

[0046] The system maintains a reversible balance of "low concentration of active growing free radicals + high concentration of dormant species". The rapid and reversible exchange of free radicals and active species allows all polymer chains to grow at almost the same rate, completely suppressing irreversible bimolecular termination and achieving active controllable polymerization.

[0047] Each growing chain has an R-terminal DMAP-PO anchoring unit at its end, which continuously enriches MA monomers around the growing free radicals, allowing MA monomers to preferentially insert into the end of the growing chain, avoiding the formation of S homopolymer blocks, and achieving precise control of the distribution of copolymer ternaries (SSS, SSM / MSS, MSM).

[0048] The growing free radicals alternately undergo double bond addition reactions with S / MA monomers. Each chain growth is accompanied by a reversible switch between dormant and active species, ensuring that the molecular weight increases linearly with monomer conversion rate and that the molecular weight distribution coefficient is [not specified]. ≤1.35.

[0049] Compared with the prior art, the beneficial effects of the present invention are:

[0050] 1. This invention solves the problem of initiator / chain transfer agent residue in existing S-MA copolymerization systems, achieving residue-free polymerization. Current technologies generally employ a separate system of "exogenous free radical initiator + independent RAFT chain transfer agent." From a polymerization mechanism perspective, the decomposition of the exogenous initiator inevitably produces free small molecule byproducts, and the RAFT reagent also leaves unreacted free residues. Even with complex post-processing such as dialysis and column chromatography, it is impossible to completely remove trace small molecule impurities encapsulated by polymer segments. This is the core reason why traditional SMA resins cannot meet the high purity requirements of the biomedical field. This invention alters the residual logic of traditional systems from the polymerization mechanism perspective. It covalently anchors the initiating unit to the Z-terminus of the RAFT reagent. The initiating free radical generated by homolytic cleavage of the peroxide bond is covalently connected to the trithiocarbonate core throughout the entire process, with no release of free small molecules. Simultaneously, after the anchoring unit, acting as a leaving group, detaches, it directly initiates monomer polymerization and covalently binds to the polymer chain end. Ultimately, the entire reagent molecule becomes 100% a covalent component of the polymer chain. No free impurities are generated throughout the polymerization process. This completely eliminates the residual source of initiators and chain transfer agents at the reaction mechanism level, allowing for the production of high-purity SMA resin without complex post-processing. This resin is suitable for the stringent purity requirements of biomedical applications such as membrane protein solubilization and drug delivery.

[0051] 2. By addressing the industry pain point of mismatched monomer reactivity rates in S-MA copolymerization systems from the perspective of polymerization growth mechanism, precise controllability of high monomer conversion rate and copolymer sequence structure is achieved. In existing S-MA copolymerization systems, there is an order-of-magnitude difference in the monomer reactivity rates of styrene and maleic anhydride. The homopolymerization and copolymerization activity of styrene is much higher than that of maleic anhydride. From the perspective of chain growth mechanism, the growing free radicals will preferentially react with styrene monomers, which can easily lead to problems such as compositional drift, low maleic anhydride conversion rate, and styrene homopolymer blocks. Ultimately, this results in large batch-to-batch performance fluctuations of copolymers, making it impossible to precisely control their interaction with the lipid bilayer. This invention introduces maleic anhydride anchoring units at the R-terminus of the RAFT reagent, thereby altering the local reaction concentration of monomers from the perspective of the chain growth microenvironment mechanism. Through dynamic hydrogen bond-ion pairing, the anchoring units can directionally enrich maleic anhydride monomers around the active free radical sites of each growing chain, increasing the local concentration of maleic anhydride around the active center by 4-6 times. This significantly reduces the apparent polymerization rate difference between the two monomers, fundamentally avoiding styrene homopolymerization side reactions and compositional drift. It increases the maleic anhydride monomer conversion rate from about 30% in the traditional system to over 65%. At the same time, the ternary sequence distribution of the copolymer can be directionally controlled by the monomer feed ratio, achieving precise customization of the copolymer's amphiphilicity and lipid vesicle solubilization properties.

[0052] 3. The reversible equilibrium mechanism of RAFT polymerization has been optimized to improve the controllability of polymerization, significantly broaden the process adaptability window, and enhance the stability and batch repeatability of the polymerization process. In existing segregated RAFT polymerization systems, the free radicals generated by the exogenous initiator are in a separate state from the RAFT reagent. From the polymerization mechanism perspective, the concentration of free radicals in the early stage of the system increases explosively, and the reversible equilibrium between dormant and active species is established slowly, which easily leads to problems such as irreversible bimolecular termination, long induction period, and wide molecular weight distribution. At the same time, the decomposition half-life of traditional initiators is fixed, which can only be adapted to a single thermal initiation process. There is no effective free radical replenishment in the later stage of polymerization, resulting in incomplete monomer conversion. The integrated initiation-chain transfer structure of this invention achieves in-situ unification of the initiation site and chain transfer site from the perspective of the RAFT equilibrium mechanism: the free radicals generated by the in-situ decomposition of the peroxide bond directly participate in the RAFT reversible addition-fracture process, which can quickly establish a stable reversible equilibrium between dormant and active species in the early stage of polymerization, effectively suppressing irreversible termination side reactions, and keeping the molecular weight distribution coefficient of the copolymer stably controlled within 1.35, with the molecular weight increasing linearly with monomer conversion rate; at the same time, the initiation unit has photo / thermal dual-response characteristics, which can be adapted to conventional industrial processes initiated by 70°C thermal initiation, and can also realize mild polymerization initiated by room temperature ultraviolet light, greatly widening the process adaptability window; in addition, the decomposition half-life of the peroxide bond is precisely matched to the long-cycle polymerization process, which can continuously and stably replenish active free radicals throughout the polymerization process, ensuring that the monomer can still be efficiently converted in the later stage of polymerization, further reducing the monomer residue in the system. Attached Figure Description

[0053] Figure 1 This is the 1H NMR spectrum of the bifunctional trithiocarbonate RAFT reagent proposed in this invention. Detailed Implementation

[0054] The technical solutions in the embodiments of the present invention will be clearly and completely described below in conjunction with existing known technologies. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments.

[0055] Example 1: The preparation method of the bifunctional trithiocarbonate RAFT reagent includes the following steps:

[0056] S1. Synthesis of bifunctional intermediate: Using 2-mercaptoethanol and carbon disulfide as raw materials, xanthate is generated by reaction under alkaline ice bath conditions, and then reacted with 2-bromoisobutyric acid. After purification, intermediate 1 with a hydroxyl group at one end and a carboxyl group at the other end is obtained.

[0057] The molar ratio of 2-mercaptoethanol, carbon disulfide, and 2-bromoisobutyric acid is 1:1.2:1.

[0058] S2, R-terminal functionalization modification: 4-Dimethylaminopyridine is reacted with 3-bromo-1-propanol to obtain a 4-dimethylaminopyridine-propoxy anchoring unit with a terminal hydroxyl group, which is then esterified with the carboxyl group of intermediate 1, and purified to obtain R-terminal functionalized intermediate 2.

[0059] The molar ratio of 4-dimethylaminopyridine to 3-bromo-1-propanol is 1:1.2; the molar ratio of 4-dimethylaminopyridine-propoxy anchoring unit to intermediate 1 is 1:1.1.

[0060] S3. Synthesis of target reagent: Cyclohexanone was reacted with tert-butyl hydrogen peroxide under acidic conditions to obtain a substituted cyclohexyl peroxy ketal initiating unit with a terminal hydroxyl group. This unit was then reacted with the terminal hydroxyl group of intermediate 2 to form an acetal. After purification, the bifunctional trithiocarbonate RAFT reagent was obtained.

[0061] The molar ratio of cyclohexanone to tert-butyl hydroperoxide is 1:2; the molar ratio of substituted cyclohexyl peroxy ketal initiating unit to intermediate 2 is 1.2:1.

[0062] A portion of the bifunctional trithiocarbonate RAFT reagent was dissolved in dimethyl sulfoxide and detected by 1H NMR spectroscopy. The results are as follows: Figure 1 As shown;

[0063] Among them, the two sets of doublets at δ8.28ppm and 6.61ppm correspond to the four hydrogens of the DMAP pyridine ring, the singlet at δ3.24ppm corresponds to the quaternary ammonium dimethyl group, and the tqt coupling system at δ4.44 / 3.17 / 2.04ppm matches the propyl structure linked by the ester bond, fully confirming the successful grafting of the R-terminal maleic anhydride anchoring unit; the singlet at δ1.31ppm corresponds to the nine hydrogens of the peroxytert-butyl group, and combined with the cyclohexylcycloalkanes multiplet, confirms the successful construction of the Z-terminal photo / thermal dual-response initiation unit; the characteristic peaks of the thiomethyl and tert-methyl groups of the trithiocarbonate core skeleton all correspond one-to-one. The spectrum has no obvious residual peaks from the raw materials. Some of the residual peaks may be cyclohexyl peroxy ketal from the acetal reaction, which can also participate in the reaction as an initiator in practical use. The free radicals after uniform arrangement will be captured by the RAFT system. Overall, the product has good purity and can be directly used in the styrene-maleic anhydride copolymerization system.

[0064] A method for preparing a low-residue styrene-maleic anhydride copolymer resin includes the following steps:

[0065] A homogeneous polymerization system was prepared by dissolving styrene monomer, maleic anhydride monomer, and difunctional trithiocarbonate RAFT reagent in an organic solvent.

[0066] RAFT controlled free radical polymerization reaction was carried out by thermal initiation under inert gas protection.

[0067] After the reaction was completed, styrene-maleic anhydride copolymer resin was obtained through precipitation, solid-liquid separation, and drying.

[0068] The molar ratio of styrene monomer to maleic anhydride monomer is 1:1, the molar ratio of the bifunctional trithiocarbonate RAFT reagent to styrene monomer is 1:50, the organic solvent is 1,4-dioxane, and the total monomer mass concentration of the polymerization system is 40 w / v.

[0069] The polymerization reaction temperature of the thermal initiation method is 80°C, and the reaction time is 20 hours.

[0070] The precipitation step uses a 1 mol / L hydrochloric acid aqueous solution as the precipitant, and the drying step is vacuum freeze drying.

[0071] Example 2: The preparation method and implementation steps are the same as in Example 1, except that:

[0072] The molar ratio of cyclohexanone to tert-butyl hydroperoxide is 1:5.

[0073] Photoinitiation is used, the molar ratio of styrene monomer to maleic anhydride monomer is 3:1, the molar ratio of the bifunctional trithiocarbonate RAFT reagent to styrene monomer is 1:200, the organic solvent is 1,4-dioxane, and the total monomer mass concentration of the polymerization system is 20w / v.

[0074] The photoinitiation method uses continuous irradiation with 365nm ultraviolet light, the polymerization reaction temperature is 25℃, and the reaction time is 4h.

[0075] The precipitation step uses a 1 mol / L hydrochloric acid aqueous solution as the precipitant, and the drying step is vacuum drying at 50°C.

[0076] Example 3: The preparation method and implementation steps are the same as in Example 1, except that:

[0077] The molar ratio of cyclohexanone to tert-butyl hydroperoxide is 1:3.

[0078] The polymerization is initiated by heat, with a molar ratio of styrene monomer to maleic anhydride monomer of 2:1, a molar ratio of the difunctional trithiocarbonate RAFT reagent to styrene monomer of 1:100, and the organic solvent being 1,4-dioxane. The total monomer mass concentration of the polymerization system is 30 w / v.

[0079] The polymerization reaction temperature for the thermal initiation method is 70°C, and the reaction time is 30 hours.

[0080] The precipitation step uses a 1 mol / L hydrochloric acid aqueous solution as the precipitant, and the drying step is vacuum drying at 50°C.

[0081] The following comparison model was also set:

[0082] Comparative Example 1: Based on Example 2, the difference is that a common trithiocarbonate RAFT reagent (S,S'-dimethyl dithiocarbonate) was used, without a Z-terminal initiating unit, with an R-terminus of alkyl, and azobisisobutyronitrile (AIBN) was added as an initiator, otherwise the same as in Example 2.

[0083] Comparative Example 2: Based on Example 2, the difference is that the R end is an alkyl group and there is no DMAP anchoring group, otherwise it is the same as Example 2.

[0084] Comparative Example 3: Based on Example 2, the difference is that a monofunctional trithiocarbonate RAFT reagent (S-(2-cyano-2-propyl)-S-dodecyl trithiocarbonyl ester) is used, which retains only the chain transfer function of the trithiocarbonate core, has a conventional leaving group (cyanopropyl) at the R end and no 4-dimethylaminopyridine-propoxy anchoring group, and no substituted cyclohexyl peroxy ketal initiating unit at the Z end. Azobisisobutyronitrile (AIBN) is added as an initiator, and the rest is the same as in Example 2.

[0085] Comparative Example 4: Traditional free radical polymerization, without RAFT control.

[0086] Performance testing: In accordance with GB / T 36214.1-5-2018 "Determination of average molecular weight and molecular weight distribution of polymers by volume exclusion chromatography", the number-average molecular weight, weight-average molecular weight and molecular weight distribution coefficient of polymers were tested.

[0087] According to GB / T 38271-2019 "Determination of Residual Styrene Monomer Content in Plastic Polystyrene (PS) and Impact-Resistant Polystyrene (PS-I) by Gas Chromatography", the limits for residual monomers, free initiators and residual solvents were determined.

[0088] The molar ratio of polymer comonomers and the ternary sequence distribution were tested according to ASTM D 6645. The results are shown in the table below:

[0089] Table 1. Performance tests of styrene-maleic anhydride copolymer resin

[0090]

[0091] Data Analysis:

[0092] This study addresses industry pain points in styrene-maleic anhydride (S-MA) copolymerization systems, such as mismatched monomer reactivity ratios, easy residue of exogenous initiators, and poor polymerization controllability. A bifunctional trithiocarbonate RAFT reagent integrating an R-terminal maleic anhydride monomer anchoring unit and a Z-terminal photo / thermal dual-response in-situ initiation unit was designed and synthesized. The comprehensive performance of this reagent was systematically verified through three process examples and four univariate elimination comparative examples.

[0093] Comparative Example 1 used S,S'-dimethyl dithiocarbonate, with symmetrical R groups (alkyl) at both ends. Although it lacks anchoring function, its re-initiation activity is moderate. Under the free radical concentration provided by AIBN, it can quickly establish a "dormant species-active species" equilibrium, achieving basic RAFT regulation. Comparative Example 3 used S-(2-cyano-2-propyl)-S-dodecyl trithiocarbonyl ester. The cyanopropyl group is a highly active leaving group, and its re-initiation rate is much faster than the chain growth rate of styrene and maleic acid. In the early stage of polymerization, a large number of R free radicals are released instantaneously and rapidly initiate monomers, resulting in excessively high local free radical concentrations. This leads to irreversible bimolecular termination side reactions, disrupting the establishment of RAFT equilibrium. Comparative Example 4 is a traditional free radical polymerization, i.e., it only has Z-terminal initiating units and no R-terminal anchoring structure.

[0094] Regarding residue control, this reagent achieves zero initiator residue. In all examples, the residues of free initiator are below the instrument detection limit of 1 ppm, which is two orders of magnitude lower than that of the traditional AIBN initiation system. At the same time, the R-terminal anchoring unit locally enriches maleic anhydride monomers through dynamic ion pair-hydrogen bonding, which greatly reduces the difference in monomer reactivity. The total monomer residues in all examples are below 0.1 wt%, and as low as 0.039 wt% under the optimal process, which is more than 10 times lower than that of the traditional system.

[0095] Regarding polymerization controllability and sequence regulation, the molecular weight distribution coefficient of the example group... The molecular weight was stabilized at 1.22-1.32, with the measured molecular weight deviating from the theoretical design value by less than 6%, achieving precise control of the molecular weight; the measured maleic anhydride molar fraction of the copolymer deviated from the theoretical value of the feed by ≤5%, with no obvious compositional drift, and the proportion of alternating ternary units was significantly increased, effectively suppressing the formation of styrene homopolymer blocks and achieving directional regulation of the sequence structure.

[0096] The differences in number-average molecular weight in Examples 1, 2, and 3 are mainly due to the differences in the monomer / RAFT reagent feed ratio ([M] / [RAFT]) and the total monomer concentration in the polymerization system.

[0097] Based on the RAFT polymerization mechanism, the theoretical number-average molecular weight can be derived from the formula. Calculations were performed. In Example 1, the molar ratio of RAFT reagent to styrene monomer was 1:50, and the molar ratio of styrene to maleic anhydride was 3:1. The theoretical number-average molecular weight was approximately 8200 g / mol, and the measured value was 8420 g / mol, with a deviation of 2.7%. In Example 2, the molar ratio of RAFT reagent to styrene monomer was 1:100, and the molar ratio of styrene to maleic anhydride was 2:1. The theoretical number-average molecular weight was approximately 19200 g / mol, and the measured value was 19520 g / mol, with a deviation of 1.7%. In Example 3, the molar ratio of RAFT reagent to styrene monomer was 1:200, and the molar ratio of styrene to maleic anhydride was 1:1. The theoretical number-average molecular weight was approximately 14500 g / mol, and the measured value was 14780 g / mol, with a deviation of 1.9%. These values ​​exceeded the 4000-10000 g / mol range specified in the claims, but demonstrated the precise controllability of the present invention's method over a wide range of molecular weights.

[0098] The above description is only a preferred embodiment of the present invention, but the scope of protection of the present invention is not limited thereto. Any equivalent substitutions or modifications made by those skilled in the art within the scope of the technology disclosed in the present invention, based on the technical solution and inventive concept of the present invention, should be covered within the scope of protection of the present invention.

Claims

1. A method for preparing a low-residue styrene-maleic anhydride copolymer resin, characterized in that, Includes the following steps: A homogeneous polymerization system was prepared by dissolving styrene monomer, maleic anhydride monomer, and difunctional trithiocarbonate RAFT reagent in an organic solvent. RAFT controlled free radical polymerization reaction is carried out under inert gas protection via thermal initiation or photoinitiation. After the reaction was completed, styrene-maleic anhydride copolymer resin was obtained through precipitation, solid-liquid separation, and drying. The bifunctional trithiocarbonate RAFT reagent is a compound having the structure shown in formula (Ⅰ): (I) Equation; In (I), the R group is connected to the thiocarbonyl carbon atom of the trithiocarbonate core through a monosulfide bond (-S-), and the Z group is connected to the thiocarbonyl carbon atom of the trithiocarbonate core through a monosulfide bond (-S-). The R group is a maleic anhydride monomer anchoring unit containing a 4-dimethylaminopyridine-propoxy structure, which can directionally enrich maleic anhydride monomers around the polymerization active center. The Z group is a dual-response in-situ initiation unit containing a substituted cyclohexyl peroxy ketal structure, which can generate initiating free radicals through thermal or phototriggered decomposition to achieve in-situ initiation of the polymerization reaction. The free radicals generated by the decomposition of the RAFT reagent are covalently connected to the Z end of the trithiocarbonate structure.

2. The method for preparing the low-residue styrene-maleic anhydride copolymer resin according to claim 1, characterized in that, (I) In the formula, the 4-dimethylaminopyridine-propoxy structure of the R group is connected to the alkyl carboxyl group at the R end of the trithiocarbonate through an ester bond to form a dimethylaminopyridine structure, and the tertiary amine group contained therein can form a dynamic hydrogen bond-ion pair with the carboxyl group of the maleic anhydride monomer. The substituted cyclohexyl peroxy ketal structure of the Z group is linked to the alkyl group at the Z end of the trithiocarbonate via an acetal bond. Its decomposition half-life in a 1,4-dioxane solvent at 70°C is 3.1 h, and it can decompose at room temperature under 365 nm ultraviolet light irradiation, achieving controllable initiation in both photo / thermal response.

3. The method for preparing the low-residue styrene-maleic anhydride copolymer resin according to claim 2, characterized in that, The preparation method of the bifunctional trithiocarbonate RAFT reagent includes the following steps: S1. Synthesis of bifunctional intermediate: Using 2-mercaptoethanol and carbon disulfide as raw materials, xanthate is generated by reaction under alkaline ice bath conditions, and then reacted with 2-bromoisobutyric acid. After purification, intermediate 1 with a hydroxyl group at one end and a carboxyl group at the other end is obtained. The molar ratio of 2-mercaptoethanol, carbon disulfide, and 2-bromoisobutyric acid is 1:1.2:

1. S2, R-terminal functionalization modification: 4-Dimethylaminopyridine is reacted with 3-bromo-1-propanol to obtain a 4-dimethylaminopyridine-propoxy anchoring unit with a terminal hydroxyl group, which is then esterified with the carboxyl group of intermediate 1, and purified to obtain R-terminal functionalized intermediate 2. The molar ratio of 4-dimethylaminopyridine to 3-bromo-1-propanol is 1:1.2; the molar ratio of 4-dimethylaminopyridine-propoxy anchoring unit to intermediate 1 is 1:1.

1. S3. Synthesis of target reagent: Cyclohexanone was reacted with tert-butyl hydrogen peroxide under acidic conditions to obtain a substituted cyclohexyl peroxy ketal initiating unit with a terminal hydroxyl group. This unit was then reacted with the terminal hydroxyl group of intermediate 2 to form an acetal. After purification, the bifunctional trithiocarbonate RAFT reagent was obtained. The molar ratio of cyclohexanone to tert-butyl hydroperoxide is 1:2-5; the molar ratio of substituted cyclohexyl peroxy ketal initiating unit to intermediate 2 is 1.2:

1.

4. The method for preparing the low-residue styrene-maleic anhydride copolymer resin according to claim 1, characterized in that, The molar ratio of styrene monomer to maleic anhydride monomer is 1-3:1, the molar ratio of the bifunctional trithiocarbonate RAFT reagent to styrene monomer is 1:50-200, the organic solvent is 1,4-dioxane, and the total monomer mass concentration of the polymerization system is 20-40 w / v.

5. The method for preparing the low-residue styrene-maleic anhydride copolymer resin according to claim 1, characterized in that, The polymerization reaction temperature of the thermal initiation method is 60-80℃, and the reaction time is 20-40h.

6. The method for preparing the low-residue styrene-maleic anhydride copolymer resin according to claim 1, characterized in that, The photoinitiation method uses continuous irradiation with 365nm ultraviolet light, the polymerization reaction temperature is 20-30℃, and the reaction time is 2-6h.

7. The method for preparing the low-residue styrene-maleic anhydride copolymer resin according to claim 1, characterized in that, The precipitation step uses a 1 mol / L hydrochloric acid aqueous solution as the precipitant, and the drying step is vacuum freeze drying or vacuum drying at 40-60℃. The resulting styrene-maleic anhydride copolymer resin does not require dialysis or column chromatography purification, the free reagent residue is less than 1 ppm, and the residual monomer content is less than 0.1 wt%.

8. The method for preparing the low-residue styrene-maleic anhydride copolymer resin according to claim 1, characterized in that, The number-average molecular weight of the obtained styrene-maleic anhydride copolymer resin was 4000-10000 g / mol, and the molecular weight distribution coefficient was [missing information]. ≤1.

35.

9. The method for preparing the low-residue styrene-maleic anhydride copolymer resin according to claim 1, characterized in that, The distribution of SSS, SSM / MSS, and MSM ternary components of the obtained styrene-maleic anhydride copolymer resin can be directionally controlled by the monomer feed ratio, and when it interacts with the lipid bilayer, it can form styrene-maleic anhydride lipid particles with a particle size of 6-9 nm.

Images