CN-122011305-A - Precise synthesis method of polymethacrylate polymer

Abstract

The invention discloses a precise synthesis method of polymethacrylate polymer. The invention overcomes the technical defects of limited mass transfer and heat transfer, uneven dispersion of catalyst and initiator, low structure control precision and the like caused by the increase of the viscosity of a system in the existing synthesis process of the polymethacrylate polymer by using a magnetic oscillation environment to regulate and control the reaction process, realizes narrow molecular weight distribution, precise control of a block structure and the like of the polymer, and has wide application prospect in autonomous and controllable preparation of high-end medicinal high polymer materials.

Inventors

• LIN ZHIQIANG
• Liu Shunchuo
• GONG LIDONG

Assignees

• 北京大学

Dates

Publication Date

20260512

Application Date

20260209

Claims (10)

1. 1. The precise synthesis method of the polymethacrylate polymer is characterized by comprising the following steps of: (1) Mixing raw materials comprising methacrylate monomers, a macromolecular initiator, a micromolecular free radical initiator, a catalyst, a chain transfer agent and a solvent to obtain an initial reaction system; (2) And (3) reacting the initial reaction system at 40-90 ℃ in a magnetic oscillation environment for 4-72 h to obtain the polymethacrylate polymer.
2. 2. The precise synthesis method of the polymethacrylate polymer according to claim 1, wherein the molar ratio of the macroinitiator to the micromolecular free radical initiator to the catalyst to the chain transfer agent to the monomer is 1 (0.5-2.0): (0.05-0.20): (0.20-0.80): (20-200).
3. 3. The precise synthesis method of the polymethacrylate polymer according to claim 1, wherein the methacrylate monomer comprises at least one of methyl methacrylate, ethyl methacrylate, dimethylaminoethyl methacrylate and hydroxyethyl methacrylate.
4. 4. The precise synthesis method of the polymethacrylate polymer according to claim 1, wherein the macroinitiator comprises a PEG-Br compound, the small-molecule free radical initiator comprises at least one of azodiisobutyronitrile, azodiisoheptonitrile, benzoyl peroxide and di-tert-butyl peroxide, and the catalyst comprises a transition metal salt.
5. 5. The precise synthesis method of the polymethacrylate polymer according to claim 1, wherein the chain transfer agent comprises at least one of 2,2 '-bipyridine, 4' -dinonyl-2, 2 '-bipyridine, tri (2-pyridylmethyl) amine and N, N, N', N '', N '' -pentamethyldiethylenetriamine.
6. 6. The method for precisely synthesizing the polymethacrylate polymer according to claim 1, wherein the solvent comprises at least one of N, N-dimethylformamide, dimethyl sulfoxide, N-methylpyrrolidone, acetonitrile, isopropanol, methanol, ethanol, 1, 4-dioxane and tetrahydrofuran.
7. 7. The precise synthesis method of the polymethacrylate polymer according to claim 1, wherein the magnetic field intensity of the magnetic oscillation periodically changes along with time, the peak value of the magnetic field intensity is in the range of 0.05-2.0T, and the frequency of the magnetic oscillation is in the range of 10-50 Hz.
8. 8. The precise synthesis method of the polymethacrylate polymer according to claim 1, wherein the magnetic field direction during the magnetic oscillation is parallel to the axis of the reaction vessel or forms an angle of 30-90 degrees; Preferably, the magnetic field direction is periodically reversed.
9. 9. A polymethacrylate polymer obtained by the process according to any one of claims 1 to 8.
10. 10. The use of the polymethacrylate polymer according to claim 9 in the preparation of pH responsive pharmaceutical excipients, drug delivery vehicles or sustained and controlled release formulations.

Description

Precise synthesis method of polymethacrylate polymer Technical Field The invention belongs to the technical field of high polymer material synthesis, and particularly relates to an accurate synthesis method of a polymethacrylate polymer. Background The polymethacrylate polymer is used as a key pH responsive medicinal polymer, and the application effect of the polymethacrylate polymer in the biomedical fields of drug delivery, sustained and controlled release preparation and the like is highly dependent on accurate molecular structure parameters, including molecular weight distribution, block sequence arrangement, composition proportion and the like. Currently, the precise synthesis of polymethacrylate polymers mostly adopts an Atom Transfer Radical Polymerization (ATRP) technology. In an ATRP system, a macromolecular initiator and a traditional free radical initiator are usually introduced at the same time, and the two have distinct and indispensable functions, wherein the traditional free radical initiator is responsible for generating free radicals to maintain catalytic activity, and the macromolecular initiator is used as an anchoring starting point for chain growth, so that the efficient start and accurate regulation of polymerization reaction are ensured together. However, in the process of preparing the polymethacrylate polymer, as the reaction advances, the viscosity of the system is increased sharply, and serious mass and heat transfer limitation problems are easy to cause: I. the uneven heat transfer induces side reactions, namely the coupling of polymerization heat release and high viscosity can form 'hot spots' (the temperature fluctuation can reach +/-5 ℃) on the part of the reactor (such as the vicinity of a stirring paddle), so that the side reactions such as chain growth deactivation, bursting polymerization and the like are caused, and the polymerization controllability is destroyed; The mass transfer limitation aggravates the viscosity sudden rise, namely the system viscosity grows exponentially along with the conversion rate, chain entanglement and the formation of local high concentration areas (such as monomer/free radical aggregation) can further reduce the fluidity of the system, resulting in the sudden drop of the mass transfer efficiency in the later stage and the stagnation of the reaction rate; And III, the uneven distribution of active species destroys the synchronism, namely a catalysis system (such as Cu 2+/Cu+ -ligand compound), a macromolecular initiator and free radicals generated by the traditional free radical initiator are easy to cause uneven spatial distribution (forming a 'rich free base region' and a 'catalyst aggregation region') due to limited mass transfer, so that the difference of chain growth rates is obvious, and the defects of widening of molecular weight distribution (PDI), deviation of block proportion from a design value (error > 5%) of a preset sequence structure, unstable polymerization dynamics and the like are finally presented. In the prior art, mass transfer and heat transfer enhancement in the ATRP polymerization process is mainly dependent on modes such as mechanical stirring and ultrasonic assistance, but has obvious limitations that the mechanical stirring can only improve macroscopic mixing, can not act on microscopic-scale catalytic component/free radical distribution, is easy to cause local excessive shearing under high viscosity to aggravate catalyst aggregation and macromolecular initiator local enrichment, has limited action depth, is easy to initiate free radical chain termination side reaction, and is difficult to realize accurate regulation and control in the polymerization process. Meanwhile, the dispersion uniformity of the catalyst in the ATRP system and the effective contact efficiency of the macromolecular initiator and the free radical directly influence the concentration stability of active species and the synchronization of chain growth, and the conventional strengthening mode cannot effectively solve the problems under a high-viscosity system. Therefore, a novel technology capable of synchronously realizing heat transfer uniformity, mass transfer enhancement and active species distribution uniformity from a microscopic scale is developed, and the method has important scientific significance and industrial application value for improving the control precision of the structure of the polymethacrylate polymer. Disclosure of Invention In order to solve at least part of the technical problems in the prior art, the invention provides a precise synthesis method of a polymethacrylate polymer. Specifically, the present invention includes the following. In a first aspect of the present invention, there is provided a method for precisely synthesizing a polymethacrylate polymer, comprising the steps of: (1) Mixing methacrylate monomers, a macromolecular initiator, a micromolecular free radical initiator, a catalyst, a chain transfer agent and