Preparation method of cyclic polymer at high concentration and prepared cyclic polymer

Abstract

The invention provides a preparation method of a cyclic polymer and the prepared cyclic polymer. The preparation method comprises the following steps: obtaining a linear polymer precursor, wherein the linear polymer precursor has a group A, a group B and a side group F; combining a compound D with at least part of the pendant group F of the linear polymer precursor, so that at least part of the pendant group F of the linear polymer precursor is converted into a charged group; carrying out chemical reaction on the group A and the group B to form a charged cyclic polymer; and optionally removing the charged groups to obtain the cyclic polymer. The preparation method of the cyclic polymer is high in universality, and various cyclic polymers can be formed by using various common monomers in the market; and the reaction process is simple, the solid content of the linear polymer precursor used in the reaction system is high, byproducts are few, and the cost of the product treatment and separation process is low.

Description

Technical Field

[0001] The invention relates to a method for preparing a cyclic polymer at high concentration and the prepared cyclic polymer, belonging to the field of polymer materials. Background Art

[0002] Cyclic polymers have attracted attention in the polymer field due to their special properties, such as viscosity, thermal properties, self-assembly and surface tension. Since the synthesis of cyclic polymers is relatively difficult, there are few reports on cyclic polymers compared with the progress made in other structural polymers. In addition, the large-scale preparation of cyclic polymers has always been one of the important problems in the polymer field.

[0003] The methods that have been developed so far mainly include the ring expansion method and the ring closing method. The ring expansion method is to first design an activated cyclic small molecule, and then gradually form a large molecular weight cyclic polymer by continuously inserting monomers into the cyclic molecule. This method can ensure the formation of a cyclic topological structure, but it has great limitations: not only does it require the individual design of the activated cyclic molecule, but it also requires the screening of the corresponding catalyst. The most important thing is that this method relies on ring-opening polymerization, so the types of monomers that can be selected are very limited, which restricts the design and synthesis of cyclic polymers.

[0004] The closed-loop method for preparing cyclic polymers is to design corresponding functional groups at the end groups of the polymer chain to undergo coupling reactions, so as to achieve the purpose of connecting the ends to form cyclic polymers. This preparation method avoids the problem of specific design and monomer selectivity required by the ring expansion method, but during the preparation process of the closed-loop method, the end groups may be connected between different molecular chains to form linear polymer chains with larger molecular weight. This side reaction not only causes the product to contain a large amount of non-cyclic polymers, but also makes separation difficult and costly. In order to avoid side reactions, it is necessary to reduce the probability of collision between molecular chains as much as possible, that is, to control the reaction under the conditions of extremely dilute solutions. In industrial production, extremely dilute solutions also mean extremely high separation and purification costs.

[0005] Reference 1 discloses a method for preparing a cyclic polymer. The preparation method comprises the following steps: 1) dissolving a polymer monomer, a chain transfer agent and an initiator in a reaction solvent, and reacting under argon protection after deoxygenation to obtain a reaction mixture system; 2) the reaction mixture system undergoes a reversible addition-fragmentation chain transfer free radical polymerization reaction under anaerobic conditions; 3) purifying the product by dialysis, and obtaining a cyclic polymer after freeze-drying. However, this method will produce a large number of by-products, so that the product contains a large number of non-cyclic polymers, and the separation is difficult and the cost is high.

[0006] Reference 2 discloses a cyclic polymer and a method for preparing the same. First, the monomer EPNA is obtained, and the monomer EPNA is gradually polymerized by a "click" reaction using a thermally catalyzed solid phase reaction to obtain a linear PEPNA with an α-azido group and an ω-ethynyl group; the linear PEPNA is subjected to a ring-closing reaction in an extremely dilute solution by an azide / ethynyl CuAAC method to obtain a cyclic PEPNA, i.e., a cyclic polymer. The extremely dilute solution refers to a linear polymer having a mass concentration of no more than 1.0×10 -4 In order to avoid side reactions and reduce the probability of collision between molecular chains as much as possible, the reaction is carried out under extremely dilute solution conditions, which requires extremely high separation and purification costs.

[0007] Therefore, the preparation of cyclic polymers with less by-products and low cost in the process of handling and separating products under high solid content conditions has become an urgent problem to be solved.

[0008] References:

[0009] Reference 1: CN114395060A

[0010] Reference 2: CN102617855A Summary of the invention

[0011] Problem that the invention aims to solve

[0012] In view of the technical problems existing in the prior art, the present invention first provides a method for preparing a cyclic polymer. The method for preparing a cyclic polymer of the present invention has strong universality, and various monomers commonly available on the market can be used to form a variety of cyclic polymers; and the reaction process is simple, the solid content of the linear polymer precursor used in the reaction system is high, the by-products are small, and the cost of processing and separating the product process is low.

[0013] Solutions for solving problems

[0014] [1] A method for preparing a cyclic polymer, comprising the following steps:

[0015] Obtaining a linear polymer precursor, wherein the linear polymer precursor has a group A, a group B, and a side group F;

[0016] combining compound D with at least part of the side groups F of the linear polymer precursor to convert at least part of the side groups F of the linear polymer precursor into charged groups;

[0017] Allowing the group A and the group B to undergo a chemical reaction to form a charged cyclic polymer;

[0018] Optionally, the charged group is removed to yield a cyclic polymer.

[0019] [2] The preparation method according to [1] above, wherein the group A is selected from one or a combination of an azide group and a halogen group; and / or,

[0020] The group B is selected from one or a combination of two or more of a substituted or unsubstituted alkynyl group, an ester group, a halogen group, a hydroxyl group, a substituted or unsubstituted amino group, and a substituted or unsubstituted amide group; and / or

[0021] The side group F is selected from one or a combination of two or more of a carboxyl group, an amino group, a halogen group, a tertiary amine group, a pyridyl group, and an imidazole group.

[0022] [3] The preparation method according to [1] or [2] above, wherein the number average molecular weight of the linear polymer precursor is 5000 g / mol-200000 g / mol, preferably 10000 g / mol-100000 g / mol.

[0023] [4] The preparation method according to any one of [1] to [3] above, wherein the compound D comprises one or a combination of two or more selected from carboxylic acid compounds, amino compounds, halogenated compounds, tertiary amine compounds, pyridine compounds, and imidazole compounds.

[0024] [5] The preparation method according to any one of [1] to [4] above, wherein the compound D reacts with a linear polymer precursor through a quaternization reaction or a salt-forming reaction to convert at least part of the side groups F of the linear polymer precursor into charged groups.

[0025] [6] The preparation method according to any one of [1] to [5] above, wherein the chemical reaction comprises one or a combination of two or more of a click reaction, a Staudinger reaction, and a coupling reaction.

[0026] [7] The preparation method according to any one of [1] to [6] above, wherein the concentration of the linear polymer precursor in the preparation system is 1-300 mg / mL, preferably 10-100 mg / mL.

[0027] [8] The preparation method according to any one of [1] to [7] above, wherein the temperature of the chemical reaction is 0-100°C, preferably 25-80°C; and the time of the chemical reaction is 1-48 hours, preferably 3-36 hours.

[0028] [9] The preparation method according to any one of [1] to [8] above, wherein the chemical reaction is carried out in a solvent; preferably, the dielectric constant of the solvent is 2.2-49, preferably 2.6-37.

[0029]

[10] A cyclic polymer prepared by the method for preparing a cyclic polymer according to any one of [1] to [9] above, wherein the diameter of the cyclic polymer is 3-100 nm.

[0030] Effects of the Invention

[0031] The preparation method of the cyclic polymer of the present invention has strong universality, and various monomers commonly available on the market can be used to form a variety of cyclic polymers; and the reaction process is simple, the solid content of the linear polymer precursor used in the reaction system is high, the by-products are small, and the cost of processing and separating the products is low. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 A comparison chart of gel permeation chromatography (GPC) curves of the linear polymer precursor and the cyclic polymer of Example 2 of the present invention is shown.

[0033] Figure 2 A comparison chart of dynamic light scattering (DLS) data of the linear polymer precursor and the cyclic polymer of Example 2 of the present invention is shown.

[0034] Figure 3 A sample picture of a cyclic polymer observed under a transmission electron microscope according to Example 2 of the present invention is shown, wherein the cyclic polymer is visualized by grafting PEO-CHO with Mn=1000. DETAILED DESCRIPTION

[0035] Various exemplary embodiments, features and aspects of the present invention will be described in detail below. The word "exemplary" used here means "used as an example, embodiment or illustrative". Any embodiment described here as "exemplary" is not necessarily interpreted as being superior or better than other embodiments.

[0036] In addition, in order to better illustrate the present invention, numerous specific details are provided in the following specific embodiments. It should be understood by those skilled in the art that the present invention can be implemented without certain specific details. In other examples, methods, means, equipment and steps well known to those skilled in the art are not described in detail in order to highlight the subject matter of the present invention.

[0037] Unless otherwise stated, the units used in this specification are all international standard units, and the numerical values ​​and numerical ranges appearing in the present invention should be understood to include the inevitable systematic errors in industrial production.

[0038] In this specification, the numerical range expressed using "a numerical value A to a numerical value B" means a range including the endpoints numerical values ​​A and B.

[0039] In the present specification, a numerical range expressed using "above" or "below" means a numerical range including the number.

[0040] In this specification, the word "may" means both performing a certain process and not performing a certain process.

[0041] In this specification, the word "optionally" is used to indicate that certain substances, components, execution steps, application conditions and other factors are used or not used.

[0042] In this specification, the unit names used are all international standard unit names, and unless otherwise stated, the "%" used indicates weight or mass percentage.

[0043] In this specification, "(meth)acrylic acid" means including both acrylic acid and methacrylic acid. In addition, in this specification, "(meth)" has the same meaning in all cases.

[0044] In the present specification, "halogen" means a "chlorine atom", a "bromine atom" or an "iodine atom".

[0045] In this specification, the references to "some specific / preferred embodiments", "other specific / preferred embodiments", "embodiments", etc., mean that the specific elements (e.g., features, structures, properties and / or characteristics) described in connection with the embodiments are included in at least one embodiment described herein, and may or may not exist in other embodiments. In addition, it should be understood that the elements may be combined in various embodiments in any suitable manner.

[0046] The present invention provides a method for preparing a cyclic polymer, wherein the preparation method uses a linear polymer precursor as a starting material for preparation. The preparation method of the cyclic polymer of the present invention has strong universality, and various monomers commonly available on the market can be used to form a variety of cyclic polymers; and the reaction process is simple, the linear polymer precursor used in the reaction system has a high solid content, a small amount of by-products, and a low cost for processing and separating the product process.

[0047] <Linear polymer precursor>

[0048] The linear polymer precursor of the present invention is formed by polymer monomers through polymerization reaction. The present invention does not specifically limit the type of polymer monomers, as long as the linear polymer precursor formed after copolymerization has group A, group B and side group F.

[0049] Specifically, in the present invention, the polymer monomer may be one or a combination of two or more of (meth)acrylic monomers, (meth)acrylamide monomers, styrene monomers and vinyl monomers.

[0050] The (meth)acrylic monomer may include (meth)acrylic acid or (meth)acrylic acid alkyl ester. As for the (meth)acrylic acid alkyl ester, there may be exemplified a linear or branched (meth)acrylic acid alkyl ester having an alkyl group with 1 to 10 carbon atoms. For example, as the alkyl group, there may be exemplified a methyl group, an ethyl group, a propyl group, an isopropyl group, a butyl group, an isobutyl group, a tert-butyl group, a pentyl group, a hexyl group, a heptyl group, a 2-ethylhexyl group, and the like.

[0051] The (meth)acrylamide monomers may include one or a combination of two or more of (meth)acrylamide, N-methylacrylamide, N,N-dimethylacrylamide, N-hydroxyethylacrylamide, N-hydroxymethylacrylamide, etc.

[0052] For styrene monomers, they may include styrene, substituted styrene, etc. For substituted styrene, the substituent may include alkyl, alkenyl, alkoxy, amino, etc., the carbon number of the alkyl, alkenyl, alkoxy is preferably 1-5, and the alkyl, alkenyl, alkoxy may further include a substituent.

[0053] As for the vinyl monomer, it may include ethylene, propylene, isopropylene, butylene, isobutylene, pentene, isopentene, butadiene and the like.

[0054] In some specific embodiments, the linear polymer precursor of the present invention can be obtained by polymerization reaction of a monomer having a side group F, a monomer having a group A, and a monomer having a group B, wherein the group A is the same as or different from the group B, the group A is different from the side group F, and the group B is different from the side group F.

[0055] In some specific embodiments, the linear polymer precursor of the present invention can be obtained by first obtaining a linear polymer through polymerization of polymer monomers, and then introducing a group A, a group B or a side group F into the linear polymer through some other chemical reactions, such as substitution reactions, as needed, to obtain a linear polymer precursor. Wherein, the group A is the same as or different from the group B, the group A is different from the side group F, and the group B is different from the side group F.

[0056] Side group F

[0057] The side group F may be selected from one or a combination of two or more of a carboxyl group, an amino group, a halogen group, a tertiary amine group, a pyridyl group, and an imidazole group.

[0058] The present invention does not specifically limit the type of monomer containing the side group F, as long as it can be copolymerized and has the above side group F. The present invention does not specifically limit the position of the side group F in the monomer, and it can replace any feasible hydrogen in the monomer.

[0059] Specifically, in the present invention, the monomer containing a side group F can be one or a combination of two or more of a (meth)acrylic monomer containing a side group F, a (meth)acrylamide monomer containing a side group F, a styrene monomer containing a side group F, and a vinyl monomer containing a side group F.

[0060] In some specific embodiments, the (meth)acrylic monomer whose side group F is a carboxyl group may be (meth)acrylic acid, carboxyethyl (meth)acrylate, carboxypentyl (meth)acrylate, and the like.

[0061] In some specific embodiments, the styrenic monomer whose side group F is a halogen can be a halogen-substituted C 1-5 Alkyl-substituted styrenes, halogen-substituted C 1-5 Alkenyl substituted styrenes, for example: 4-chloromethylstyrene (VBC), 4-chloroethylstyrene, 4-bromomethylstyrene, 4-bromoethylstyrene, etc. The styrene monomer whose side group F is an amino group can be an amino substituted styrene monomer, and preferably the amino group can be protected by a protecting group, specifically by a tert-butyloxycarbonyl group, for example tert-butyl 4-vinylphenylcarbamate (AStBoc).

[0062] In some specific embodiments, the vinyl monomer whose side group F is a pyridyl group may be 2-vinylpyridine or the like.

[0063] In some specific embodiments, the vinyl monomer whose side group F is an imidazole group may be 2-vinylimidazole or the like.

[0064] In some specific embodiments, the (meth)acrylic monomer whose side group F is a tertiary amine group may be 2-aminoethyl methacrylate or a salt thereof, such as 2-aminoethyl methacrylate hydrochloride (AMA) and the like.

[0065] Group A

[0066] The group A of the present invention may refer to the terminal group A of the linear polymer precursor. The group A may be one or a combination of two selected from an azide group and a halogen group. The group A of the present invention may be introduced by directly using a monomer containing the group A, for example, the group A may be introduced by a monomer containing a halogen group; the group A of the present invention may also be introduced by a substitution reaction after obtaining a linear polymer, for example, an azide group is introduced after obtaining a linear polymer; of course, the present invention may also be to first introduce the group A into the monomer by a substitution reaction, and then to perform a polymerization reaction.

[0067] In the present invention, the monomer containing group A can be one or a combination of two or more of a (meth) acrylic monomer containing group A, a (meth) acrylamide monomer containing group A, a styrene monomer containing group A, and a vinyl monomer containing group A. The monomer containing group A of the present invention has the same selectable range as the monomer containing side group F, but the monomer containing group A of the present invention can be different from the monomer containing side group F. For example, when group A is halogen, side group F may not be halogen.

[0068] In some specific embodiments, when group A is an azido group, it can be obtained by subjecting a linear polymer to a substitution reaction with an azide salt, so that the linear polymer first has an azido group. Preferably, the linear polymer may have a halogen, and the halogen is substituted with an azido group by using an azide salt.

[0069] In some specific embodiments, when group A is an azido group, a linear polymer can be obtained first, and then the linear polymer is subjected to a substitution reaction with an azide salt to obtain a linear polymer precursor having an azido group.

[0070] In some specific embodiments, the styrene monomer in which group A is halogen can be halogen-substituted C 1-5 Alkyl-substituted styrenes, halogen-substituted C 1-5 Alkenyl-substituted styrenes, for example, 4-chloromethylstyrene (VBC), 4-chloroethylstyrene, 4-bromomethylstyrene, 4-bromoethylstyrene, and the like.

[0071] Group B

[0072] The group B of the present invention may refer to the end group B of a linear polymer precursor. In the present invention, the group A and the group B may be the same or different. For the group B, it may be selected from one or more combinations of substituted or unsubstituted alkynyl, ester group, halogen, hydroxyl, substituted or unsubstituted amino, substituted or unsubstituted amide group. Wherein the carbon number of the alkynyl group may be 1-5. For substituents, the substituents may include alkyl, alkenyl, alkoxy, etc., and the carbon numbers of the alkyl, alkenyl, and alkoxy groups are preferably 1-5, and the alkyl, alkenyl, and alkoxy groups may further include substituents.

[0073] In some specific embodiments, the styrene monomer in which group B is halogen may be halogen-substituted C 1-5 Alkyl-substituted styrenes, halogen-substituted C 1-5 Alkenyl-substituted styrenes, for example, 4-chloromethylstyrene (VBC), 4-chloroethylstyrene, 4-bromomethylstyrene, 4-bromoethylstyrene, and the like.

[0074] In some specific embodiments, since the (meth)acrylic acid alkyl ester monomer contains an ester group, the monomer having a group B may be a (meth)acrylic acid alkyl ester monomer. Examples include linear or branched (meth)acrylic acid alkyl esters having an alkyl group with 1 to 10 carbon atoms. For example, examples of the alkyl group include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, tert-butyl, pentyl, hexyl, cyclohexyl, heptyl, 2-ethylhexyl, and the like.

[0075] In some specific embodiments, group B is an alkynyl (meth)acrylate monomer, which may be a (meth)acrylate monomer in which at least one H is substituted by an alkynyl group. In addition, the alkynyl group of the present invention may be protected by a protecting group, specifically, by a trimethylsilyl group, for example: 3-trimethylsilylpropynyl methacrylate.

[0076] In some specific embodiments, the group B is an alkyl (meth)acrylate monomer in which the amino group is present, and at least one H in the above alkyl (meth)acrylate monomer is substituted by an amino group, for example, 2-aminoethyl methacrylate.

[0077] In some specific embodiments, group B is a (meth)acrylic acid alkyl ester monomer having a hydroxyl group, which may be a (meth)acrylic acid alkyl ester monomer in which at least one H is substituted by a hydroxyl group, for example, hydroxyethyl methacrylate.

[0078] In some specific embodiments, since the (meth)acrylamide monomer contains an amide group, the monomer having group B may be a (meth)acrylamide monomer. Specifically, it may include one or a combination of two or more of (meth)acrylamide, N-methylacrylamide, N,N-dimethylacrylamide, N-hydroxyethylacrylamide, N-hydroxymethylacrylamide, etc.

[0079] Polymerization

[0080] The polymerization reaction of the present invention can be obtained by solution polymerization, and the polymerization modes include random copolymerization, alternating copolymerization, block copolymerization and the like.

[0081] In some specific embodiments, the polymerization reaction includes polymerizing the polymer monomers in a solvent in the presence of a RAFT agent and an initiator, thereby obtaining a linear polymer precursor. The polymerization reaction of the present invention can be obtained by simultaneously polymerizing the monomers having a side group F, the monomers having a group A, and the monomers having a group B; or the monomers having a side group F and the monomers having a group A are first polymerized, and then polymerized with the monomers having a group B; or the monomers having a side group F and the monomers having a group B are first polymerized, and then polymerized with the monomers having a group A. Of course, the polymerization reaction of the present invention can also be to first polymerize the polymer monomers to obtain a linear polymer, and then introduce the group A, the group B, and the side group F.

[0082] The present invention does not specifically limit the RAFT agent, and it can be a RAFT agent commonly used in the art. Preferably, the RAFT agent can be CPADB or D-CPADB, and the specific compounds are as follows:

[0083]

[0084] The initiator may be one or a combination of two or more selected from organic peroxides and azo compounds. The organic peroxide is preferably dibenzoyl peroxide, diisopropyl peroxide, di-tert-butyl peroxide, tert-butyl benzoyl peroxide, methyl ethyl ketone peroxide, dodecyl peroxide, tert-butyl perbenzoate, diisopropyl peroxydicarbonate, etc.; the azo compound is preferably azobisisobutyronitrile, azobisisoheptanenitrile, azobisisovaleronitrile, azobiscyclohexylcarbonitrile, dimethyl azobisisobutyrate, etc.

[0085] The present invention does not specifically limit the solvent, and it can be an organic solvent or water commonly used in the art, preferably an organic solvent. Examples thereof include ketones such as acetone, methyl ethyl ketone, dimethyl acetone, methyl isobutyl ketone, acetophenone, and N-methyl-2-pyrrolidone, ethers such as tetrahydrofuran and dioxane, aromatic hydrocarbons such as benzene, toluene, xylene, and chlorobenzene, and amides such as N,N-dimethylformamide and N,N-dimethylacetamide.

[0086] The conditions for the polymerization reaction are not particularly limited in the present invention and can be selected as needed, as long as the desired linear polymer precursor can be obtained. Generally speaking, the polymerization reaction time can be 1-24 hours at a temperature of 50-100° C. to obtain a polymerization product. As needed, a group A, a group B or a side group F is introduced into the polymerization product. Finally, after separation treatment, a linear polymer precursor is obtained.

[0087] The present invention does not specifically limit the separation method, which may be a commonly used separation method in the art, such as using n-hexane to precipitate the linear polymer precursor. Preferably, the polymerization reaction is carried out in an anaerobic environment, and generally, a freeze-pump-thaw cycle of 1 to 5 times may be used for deoxygenation treatment.

[0088] In some specific embodiments, the number average molecular weight of the linear polymer precursor is 5000-200000 g / mol, preferably 10000-100000 g / mol.

[0089] <Method for producing cyclic polymer>

[0090] The preparation method of the cyclic polymer of the present invention is carried out using a linear polymer precursor having a side group F, a group A and a group B as a starting material. It may include the following steps:

[0091] (1) combining compound D with at least part of the side groups F of the linear polymer precursor, so that at least part of the side groups F of the linear polymer precursor are converted into charged groups;

[0092] (2) causing the group A and the group B to undergo a chemical reaction to form a charged cyclic polymer;

[0093] (3) Optionally removing the charged group to obtain a cyclic polymer.

[0094] Step (1)

[0095] Compound D is combined with at least part of the side groups F of the linear polymer precursor to convert at least part of the side groups F of the linear polymer precursor into charged groups. Step (1) of the present invention introduces charged groups into the side groups of the linear polymer precursor, thereby making the linear polymer precursor charged. In this process, the linear polymer precursor is treated to make it charged, so that repulsion is generated between the polymer chains of the linear polymer precursor, and the magnitude of the interchain repulsion force generated by different charge amounts is different. This repulsion effectively reduces the side reactions between the molecular chains during the cyclization process, creates conditions for the subsequent intramolecular reaction of the group A and the group B, thereby achieving product preparation at high concentration.

[0096] In some specific embodiments, the compound D and the linear polymer precursor are reacted by quaternization reaction or salt formation reaction to convert at least part of the side groups F of the linear polymer precursor into charged groups. Taking the salt formation reaction (acid-base reaction) as an example, the side groups F of the linear polymer precursor are acidic or basic groups, and the compound D is a base or an acid accordingly (i.e., the reactive group of the compound D that can react with the side groups F is a basic or acidic group).

[0097] In some specific embodiments, the side group F is selected from one or a combination of two or more of a carboxyl group, an amino group, a halogen group, a tertiary amine group, a pyridyl group, and an imidazole group.

[0098] Compound D can be any compound as long as it has a group that can react with the side group F to convert it into a charged group. Exemplarily, the compound D includes one or a combination of two or more selected from carboxylic acid compounds, amino compounds, halogenated compounds, tertiary amine compounds, pyridine compounds, and imidazole compounds. Specifically, compound D can be trifluoroacetic acid, iodoethane, methylimidazole, pyridine, etc.

[0099] Preferably, the combination of the side group F of the linear polymer precursor / the reactive group of the compound D can be a combination selected from the following: carboxyl / amino, amino / carboxyl, halogen / tertiary amine, halogen / pyridine, halogen / imidazole, tertiary amine / halogen, pyridine / halogen, imidazole / halogen, etc.

[0100] Here, of the two groups separated by the symbol “ / ”, the group before the symbol “ / ” is the side group F of the linear polymer precursor, and the group after the symbol “ / ” is the reactive group of the compound D.

[0101] In step (1), a portion of the side groups F of the linear polymer precursor may be converted into charged groups, while the other portion remains in the form of side groups F; or all of the side groups F may be converted into charged groups. In some specific embodiments, after the reaction of step (1) is completed, the proportion of the side groups F converted into charged groups may be 10% to 100% by mole, preferably 60% to 100% by mole.

[0102] In some specific embodiments, step (1) is performed in a solvent. Specifically, the linear polymer precursor is dissolved in a solvent, and then compound D is added, and optionally stirred to react. The stirring time is not particularly limited in the present invention, and can generally be 10-60 minutes.

[0103] The present invention does not specifically limit the solvent, and it can be an organic solvent or water commonly used in the art. Further, the dielectric constant of the solvent is 2.2-49, preferably 2.6-37. Preferably, the solvent is an organic solvent. For example, organic solvents include ketones such as acetone, methyl ethyl ketone, dimethyl acetone, methyl isobutyl ketone, acetophenone, N-methyl-2-pyrrolidone, ethers such as tetrahydrofuran and dioxane, aromatic hydrocarbons such as benzene, toluene, xylene, chlorobenzene, amides such as N,N-dimethylformamide and N,N-dimethylacetamide, etc.

[0104] Furthermore, the present invention does not impose any particular limitation on the reaction temperature of step (1), which may be carried out at 10-50°C.

[0105] In addition, it should be noted that when preparing a linear polymer precursor, when the linear polymer precursor needs to introduce an azide group, it can be carried out simultaneously with step (1), or the azide group can be introduced first and then step (1). Furthermore, in order to speed up the reaction efficiency, it is preferred that the introduction of the azide group and step (1) are carried out simultaneously.

[0106] Step (2)

[0107] The group A and the group B are chemically reacted to form a charged cyclic polymer. The group A and the group B are a group combination that can react with each other to form a covalent bond, and the two groups can be the same or different.

[0108] Preferably, group A / group B is selected from the following combinations: azide / alkynyl, azide / ester, halogen / halogen, halogen / hydroxyl, halogen / amino, halogen / amide, and the like.

[0109] In the group combination described herein, one of the two groups separated by the symbol “ / ” is group A and the other is group B, and the order of appearance is not limited.

[0110] Step (3) is carried out under conditions that allow group A and group B to undergo a chemical reaction, for example, in the presence of a catalyst.

[0111] In some specific embodiments, the chemical reaction may include one or a combination of two or more of a click reaction, a Staudinger reaction, and a coupling reaction.

[0112] In a specific embodiment, group A / group B is halogen / halogen. In this case, step (3) can be carried out in the presence of a catalyst, which can prepare a charged cyclic polymer through a coupling reaction.

[0113] In a specific embodiment, group A / group B is an azide / alkyne group. In this case, step (3) can be carried out in the presence of a catalyst, and a charged cyclic polymer can be prepared by a click reaction.

[0114] In a specific embodiment, group A / group B is an azide / ester group. In this case, step (3) can be carried out in the presence of a catalyst, and a charged cyclic polymer can be prepared by a Staudinger reaction.

[0115] In a specific embodiment, group A / group B is halogen / hydroxyl, which can be prepared into a charged cyclic polymer through a coupling reaction.

[0116] In a specific embodiment, group A / group B is halogen / amino, which can be prepared by coupling reaction to obtain a charged cyclic polymer.

[0117] In a specific embodiment, group A / group B is a halogen / amide group, which can be prepared into a charged cyclic polymer through a coupling reaction.

[0118] The present invention does not specifically limit the catalyst, and the required catalyst can be selected according to the specific reaction. Among them, the catalyst for the coupling reaction can be triphenylphosphine palladium and carbonate, such as triphenylphosphine palladium and cesium carbonate, etc.; the catalyst for the Staudinger reaction can be triphenylphosphine; the catalyst for the click reaction can be cuprous halide, such as cuprous bromide, etc.

[0119] In some specific embodiments, in the chemical reaction system, the concentration of the reactants is 1 mg / mL-300 mg / mL, preferably 10-100 mg / mL.

[0120] In some specific embodiments, the temperature of the chemical reaction may be 0-100° C., preferably 25-80° C., and the time of the chemical reaction may be 1-48 hours, preferably 3-36 hours.

[0121] Step (3)

[0122] Finally, the charged groups are optionally removed to obtain a cyclic polymer. As required, the present invention can remove the charged groups and obtain the cyclic polymer by a post-treatment method such as precipitation and washing. Of course, the present invention may not remove the charged groups. Only a post-treatment method such as precipitation and washing is used to obtain a charged cyclic polymer.

[0123] The present invention does not particularly limit the method for removing the charged group. Generally, when an acidic compound D is used, a basic compound is used to remove it, and when a basic compound D is used, an acidic compound can be used to remove it.

[0124] For example, when trifluoroacetic acid is used as compound D, saturated NaHCO 3 washing can be used to remove compound D.

[0125] In addition, the catalyst can be removed by washing with water or during precipitation. For example, triphenylphosphine palladium can be removed by using heated cyclohexane to precipitate the cyclic polymer. When cuprous bromide is used as the catalyst, water dialysis can be used to remove copper ions.

[0126] <Cyclic polymer>

[0127] The present invention also provides a cyclic polymer, which is prepared by the method for preparing a cyclic polymer according to the present invention, and preferably, the diameter of the cyclic polymer is 3-100 nm. The diameter of the cyclic polymer of the present invention can be obtained by measuring the distance using a transmission electron microscope (TEM) and by determining the diameter using dynamic light scattering (DLS).

[0128] Example

[0129] The embodiments of the present invention will be described in detail below in conjunction with the examples, but those skilled in the art will appreciate that the following examples are only used to illustrate the present invention and should not be considered to limit the scope of the present invention. If no specific conditions are specified in the examples, they are carried out according to normal conditions or the conditions recommended by the manufacturer. If the manufacturer is not specified for the reagents or instruments used, they are all conventional products that can be obtained commercially.

[0130] Example 1

[0131] Add 10mmol methacrylic acid (MAA), 0.02mmol azobisisobutyronitrile (AIBN), 0.1mmol RAFT agent D-CPADB, 0.2mmol 4-chloromethylstyrene (VBC) and 2mL dioxane to a 25mL test tube, stir evenly, and freeze-evacuate-thaw three times to deoxygenate. Heat at 80℃ for 8h to polymerize. After the reaction is completed, cool and terminate the reaction to obtain the reaction product. The reaction product is precipitated in n-hexane, washed three times and dried to obtain a pink linear polymer PVBC-b-PMAA-b-PVBC, i.e., a linear polymer precursor.

[0132] Take the above linear polymer in a test tube, add 1 mL of dimethylformamide (DMF), add 2 mmol of methylimidazole after dissolution, and stir for 30 minutes to charge the linear polymer. Then add 1% triphenylphosphine palladium and 1% cesium carbonate (based on the total mass of the reactants) as catalysts, react for 12 hours, and make the linear polymer undergo coupling reaction at 80°C to achieve cyclization. After the coupling reaction, use 60°C n-hexane to precipitate the cyclic polymer and remove the charged groups at the same time, then wash with water to remove cesium carbonate, and dry to obtain the cyclic polymer.

[0133] The structural formula of the RAFT agent D-CPADB used is as follows:

[0134]

[0135] Example 2

[0136] Add 1mmol methyl methacrylate (MMA), 0.02mmol azobisisobutyronitrile (AIBN), 0.1mmol RAFT agent CPADB, 10mmol tert-butyl 4-vinylphenylcarbamate (AStBoc), and 2mL dioxane into a 50mL test tube, stir evenly, freeze-evacuate-thaw cycle three times to deoxygenate. Heat at 80℃ for 8h to perform block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the first reaction product. The first reaction product is precipitated in n-hexane, washed three times and dried to obtain a pink linear polymer PMMA-b-PAStBoc.

[0137] Take the above linear polymer PMMA-b-PAStBoc in a test tube, add 0.02mmol azobisisobutyronitrile (AIBN), 0.2mmol 4-chloromethylstyrene (VBC) and 2mL dioxane, stir evenly, freeze-evacuate-thaw three times to deoxygenate. Heat at 80℃ for 8h and then carry out block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the second reaction product. The second reaction product is precipitated in n-hexane, washed three times and dried to obtain a pink linear polymer PMMA-b-PAStBoc-b-PVBC.

[0138] The linear polymer PMMA-b-PAStBoc-b-PVBC was placed in a test tube, 0.2 mmol NaN3, 5 mmol trifluoroacetic acid and 1 mL dimethylformamide were added, and the reaction was continued for 24 hours to obtain a third reaction product. The third reaction product was precipitated in n-hexane, washed three times, and dried to obtain a linear polymer PMMA-b-PStNH2-b-PVBC with an azide terminal and a charge, i.e., a linear polymer precursor.

[0139] Take the above-mentioned linear polymer PMMA-b-PStNH2-b-PVBC with azide at the end and charge in a test tube, add 1mL dimethylformamide (DMF) to dissolve, add 0.2mmol catalyst triphenylphosphine, stir for 30min, then add 0.6mmol catalyst triphenylphosphine and heat to 40℃ to carry out Staudinger reaction, and react for 8h to achieve cyclization. After the reaction is completed, wash with saturated NaHCO3 to remove the charged group and precipitate and dry in n-hexane at 60℃ to remove triphenylphosphine, and a cyclic polymer can be obtained.

[0140] The structural formula of the RAFT agent CPADB used is as follows:

[0141]

[0142] Example 3

[0143] Add 0.2mmol 3-trimethylsilylpropynyl methacrylate (NMA), 0.02mmol azobisisobutyronitrile, 0.1mmol RAFT agent CPADB, 10mmol tert-butyl 4-vinylphenylcarbamate (AStBoc), and 2mL dioxane to a 50mL test tube, stir evenly, and freeze-evacuate-thaw three times to deoxygenate. Heat at 80℃ for 8h for block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the first reaction product. The first reaction product is precipitated in n-hexane, washed three times and dried to obtain a pink linear polymer PNMA-b-PAStBoc.

[0144] Take the above polymer in a test tube, add 0.02mmol azobisisobutyronitrile, 0.2mmol 4-chloromethylstyrene and 2mL dioxane, stir evenly, freeze-evacuate-thaw three times to deoxygenate. Heat at 80℃ for 8h and then carry out block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the second reaction product. The second reaction product is precipitated in n-hexane, washed three times and dried to obtain a pink linear polymer PNMA-b-PAStBoc-b-PVBC, i.e., a linear polymer precursor.

[0145] The linear polymer PNMA-b-PAStBoc-b-PVBC was placed in a test tube, 0.2 mmol NaN3 and 5 mmol trifluoroacetic acid were added, and the reaction was continued for 24 hours to obtain a third reaction product. The third reaction product was precipitated in n-hexane, washed three times, and dried to obtain a linear polymer PNMA-b-PStNH2-b-PVBC with an azide terminal and a charge.

[0146] The linear polymer PNMA-b-PStNH2-b-PVBC with azide at the end and a charge was placed in a test tube, 1 mL of dimethylformamide (DMF) was added to dissolve it, and then 0.2 mmol of catalyst cuprous bromide was added to perform a click reaction at room temperature. The reaction lasted for 24 hours to achieve cyclization. After the reaction, the charged groups were removed by washing with saturated NaHCO3 and the copper ions were removed by dialysis with deionized water to obtain a cyclic polymer.

[0147] Example 4

[0148] Add 0.2mmol hydroxyethyl methacrylate (HEMA), 0.02mmol azobisisobutyronitrile, 0.1mmol RAFT agent CPADB, 10mmol methacrylic acid (AA), and 2mL dioxane into a 50mL test tube, stir evenly, freeze-evacuate-thaw three times to deoxygenate. Heat at 80℃ for 8h to perform block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the first reaction product. The first reaction product is precipitated in n-hexane, washed three times and dried to obtain a pink linear polymer PHEMA-b-PAA.

[0149] Take the above polymer in a test tube, add 0.02mmol azobisisobutyronitrile, 0.1mmol 4-chloromethylstyrene and 2mL dioxane, stir evenly, freeze-evacuate-thaw three times to deoxygenate. Heat at 80℃ for 8h and then carry out block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the second reaction product. The second reaction product is precipitated in n-hexane, washed three times and dried to obtain a pink linear polymer PHEMA-b-PAA-b-PVBC, i.e., a linear polymer precursor.

[0150] Take the above linear polymer PHEMA-b-PAA-b-PVBC in a test tube, add 1 mL of dimethylformamide to dissolve it, then add 5 mmol of methylimidazole, stir for 30 minutes to charge the linear polymer, then add 1% triphenylphosphine palladium and 1% cesium carbonate (based on the total mass of the reactants) as catalysts, and make the linear polymer undergo coupling reaction at 80°C. The coupling reaction is carried out for 24 hours to achieve cyclization. After the coupling reaction is completed, use 60°C n-hexane to precipitate the cyclic polymer and remove the charged groups at the same time, then wash with water to remove cesium carbonate, and then dry to obtain the cyclic polymer.

[0151] Example 5

[0152] Add 0.2mmol 2-aminoethyl methacrylate hydrochloride (AMA), 0.02mmol azobisisobutyronitrile (AIBN), 0.1mmol RAFT agent CPADB, 10mmol methacrylic acid (AA), and 2mL dioxane into a 50mL test tube, stir evenly, and freeze-evacuate-thaw three times to deoxygenate. Heat at 80℃ for 8h to perform block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the first reaction product. The first reaction product is precipitated in n-hexane, washed three times and dried to obtain a pink linear polymer PAMA-b-PAA.

[0153] Take the above linear polymer in a test tube, add 0.02mmol azobisisobutyronitrile (AIBN), 0.2mmol 4-chloromethylstyrene (VBC) and 2mL dioxane, stir evenly, freeze-evacuate-thaw three times to deoxygenate. Heat at 80℃ for 8h and then carry out block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the second reaction product. The second reaction product is precipitated in n-hexane, washed three times and dried to obtain a pink linear polymer PAMA-b-PAA-b-PVBC, i.e., a linear polymer precursor.

[0154] Take the above linear polymer PAMA-b-PAA-b-PVBC in a test tube, add 1 mL of dimethylformamide (DMF) to dissolve it, then add 5 mmol of methylimidazole and stir for 30 minutes to charge the linear polymer. Then add 1% triphenylphosphine palladium and 1% cesium carbonate (based on the total mass of the reactants) as catalysts, and make the linear polymer undergo coupling reaction at 80°C. The coupling reaction is carried out for 24 hours to achieve cyclization. After the coupling reaction is completed, use 60°C n-hexane to precipitate the cyclic polymer and remove the charged groups at the same time, then wash with water to remove cesium carbonate, and then dry to obtain the cyclic polymer.

[0155] Example 6

[0156] Add 0.2mmol methacrylamide (MAAN), 0.02mmol azobisisobutyronitrile (AIBN), 0.1mmol RAFT agent CPADB, 10mmol methacrylic acid (AA), and 2mL dioxane into a 50mL test tube, stir evenly, and freeze-evacuate-thaw three times to deoxygenate. Heat at 80℃ for 8h to perform block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the first reaction product. The first reaction product is precipitated in n-hexane, washed three times, and dried to obtain a pink linear polymer PMAAN-b-PAA.

[0157] Take the above pink linear polymer PMAAN-b-PAA in a test tube, add 0.02mmol azobisisobutyronitrile (AIBN), 0.2mmol 4-chloromethylstyrene (VBC) and 2mL dioxane, stir evenly, and freeze-evacuate-thaw three times to deoxygenate. Heat at 80℃ for 8h and then carry out block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the second reaction product. The second reaction product is precipitated in n-hexane, washed three times and dried to obtain a pink linear polymer PMAAN-b-PAA-b-PVBC, i.e., a linear polymer precursor.

[0158] Take the pink linear polymer PMAAN-b-PAA-b-PVBC in a test tube, add 1 mL of dimethylformamide (DMF) to dissolve it, then add 5 mmol of methylimidazole, stir for 30 minutes to charge the linear polymer, then add 1% triphenylphosphine palladium and 1% cesium carbonate (based on the total mass of the reactants) as catalysts, and make the linear polymer undergo coupling reaction at 80°C. The coupling reaction is carried out for 24 hours to achieve cyclization. After the coupling reaction is completed, use 60°C n-hexane to precipitate the cyclic polymer and remove the charged groups at the same time, then wash with water to remove cesium carbonate, and then dry to obtain the cyclic polymer.

[0159] Example 7

[0160] Add 1mmol methyl methacrylate (MMA), 0.02mmol azobisisobutyronitrile (AIBN), 0.1mmol RAFT agent CPADB, 10mmol 2-vinylpyridine (2VP), and 2mL dioxane into a 50mL test tube, stir evenly, and freeze-evacuate-thaw for three times to deoxygenate. Heat at 80℃ for 8h to perform block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the first reaction product. The first reaction product is precipitated in n-hexane, washed three times, and dried to obtain a pink linear polymer PMMA-b-P2VP.

[0161] Take the above linear polymer PMMA-b-P2VP in a test tube, add 0.02mmol azobisisobutyronitrile (AIBN), 0.2mmol 4-chloromethylstyrene (VBC) and 2mL dioxane, stir evenly, freeze-evacuate-thaw three times to deoxygenate. Heat at 80℃ for 8h and then carry out block copolymerization. After the reaction is completed, cool and terminate the reaction to obtain the second reaction product. The second reaction product is precipitated in n-hexane, washed three times and dried to obtain a pink linear polymer PMMA-b-P2VP-b-PVBC, i.e., a linear polymer precursor.

[0162] The linear polymer PMMA-b-P2VP-b-PVBC was placed in a test tube, 0.2 mmol NaN3, 10 mmol iodoethane and 1 mL dimethylformamide were added, and the reaction was continued for 24 hours to obtain a third reaction product. The third reaction product was precipitated in n-hexane, washed three times, and dried to obtain a linear polymer PMMA-b-P2VP-b-PVBC with an azide terminal and a charge.

[0163] Take the above-mentioned linear polymer PMMA-b-P2VP-b-PVBC with azide at the end and charge in a test tube, add 1mL dimethylformamide (DMF) to dissolve, then add 0.2mmol catalyst triphenylphosphine, stir for 30min, then add 0.6mmol catalyst triphenylphosphine and heat to 40℃ to perform Staudinger reaction, and react for 8h to achieve cyclization. After the reaction is completed, wash with saturated NaHCO3 to remove the charged group and precipitate and dry in n-hexane at 60℃ to remove triphenylphosphine, and a cyclic polymer can be obtained.

[0164] Characterization

[0165] 1. GPC test

[0166] Gel permeation chromatography (GPC) test was performed on Example 2, and the results were as follows: Figure 1 shown. Figure 1 The figure shows the comparison of the gel permeation chromatography (GPC) curves of the linear polymer precursor and the cyclic polymer of Example 2 of the present invention. Figure 1 It can be seen that after cyclization, the GPC curve shifted slightly to the right, which is consistent with the characteristics of cyclic polymers.

[0167] 2. DLS test

[0168] Dynamic light scattering (DLS) test was performed on Example 2, and the results were as follows Figure 2 shown. Figure 2 The dynamic light scattering (DLS) data comparison diagram of the linear polymer precursor and the cyclic polymer of Example 2 of the present invention is shown. Figure 2 It can be seen that the average particle size of the cyclic polymer is smaller than that of the linear polymer precursor, which further illustrates that the method of the present invention prepares a cyclic polymer.

[0169] 3. TEM test

[0170] The sample image of the cyclic polymer was observed using a transmission electron microscope for Example 2. The cyclic polymer was visualized by grafting PEO-CHO with Mn=1000. Figure 3 The sample picture of the cyclic polymer observed under a transmission electron microscope in Example 2 of the present invention is shown. Figure 3 It can be seen that the method of the present invention prepares a cyclic polymer.

[0171] Industrial Applicability

[0172] Cyclic polymers have no end groups and have smaller viscosity and fluid dynamic volume, so they have different physical and chemical properties from linear polymers. Cyclic polymers are not easy to entangle, can pass through some human organs better, and have better permeability and retention effects, thereby achieving targeted drug delivery. Since there are no end groups, the chemical properties are more stable, so they have a longer circulation time in the blood circulation and can be used to load sustained-release drugs. Based on the characteristics of no end groups, cyclic polymers can overcome some common shortcomings of drugs, including low selectivity caused by rapid metabolism, low cell permeability, and insufficient conformational flexibility and stability, thereby achieving the development of new drugs. In addition, by incorporating azobenzene repeating units into the main chain of cyclic polymers, photoisomerization capabilities can be generated, which is expected to be used in potential optical data storage and liquid crystal displays.

[0173] It should be noted that, although the technical solution of the present invention is introduced with specific examples, those skilled in the art will appreciate that the present invention should not be limited thereto.

[0174] The embodiments of the present invention have been described above, and the above description is exemplary, not exhaustive, and is not limited to the disclosed embodiments. Many modifications and variations will be apparent to those of ordinary skill in the art without departing from the scope and spirit of the described embodiments. The selection of terms used herein is intended to best explain the principles of the embodiments, practical applications, or technical improvements in the market, or to enable other persons of ordinary skill in the art to understand the embodiments disclosed herein.

Claims

1. A method for preparing a cyclic polymer, characterized in that: The following steps are involved: Obtaining a linear polymer precursor, wherein the linear polymer precursor has a group A, a group B, and a side group F; combining compound D with at least part of the side groups F of the linear polymer precursor to convert at least part of the side groups F of the linear polymer precursor into charged groups; Allowing the group A and the group B to undergo a chemical reaction to form a charged cyclic polymer; Optionally, the charged group is removed to yield a cyclic polymer.

2. The preparation method according to claim 1, characterized in that: The group A is selected from one or a combination of azido and halogen; and / or, The group B is selected from one or a combination of two or more of a substituted or unsubstituted alkynyl group, an ester group, a halogen group, a hydroxyl group, a substituted or unsubstituted amino group, and a substituted or unsubstituted amide group; and / or The side group F is selected from one or a combination of two or more of a carboxyl group, an amino group, a halogen group, a tertiary amine group, a pyridyl group, and an imidazole group.

3. The preparation method according to claim 1 or 2, characterized in that: The number average molecular weight of the linear polymer precursor is 5000 g / mol-200000 g / mol, preferably 10000 g / mol-100000 g / mol.

4. The preparation method according to any one of claims 1 to 3, characterized in that The compound D includes one or a combination of two or more selected from carboxylic acid compounds, amino compounds, halogenated compounds, tertiary amine compounds, pyridine compounds, and imidazole compounds.

5. The preparation method according to any one of claims 1 to 4, characterized in that: The compound D reacts with the linear polymer precursor through a quaternization reaction or a salt-forming reaction to convert at least part of the side groups F of the linear polymer precursor into charged groups.

6. The preparation method according to any one of claims 1 to 5, characterized in that: The chemical reaction includes one or a combination of two or more of a click reaction, a Staudinger reaction, and a coupling reaction.

7. The preparation method according to any one of claims 1 to 6, characterized in that: In the preparation system, the concentration of the linear polymer precursor is 1-300 mg / mL, preferably 10-100 mg / mL.

8. The preparation method according to any one of claims 1 to 7, characterized in that: The temperature of the chemical reaction is 0-100° C., preferably 25-80° C.; the time of the chemical reaction is 1-48 hours, preferably 3-36 hours.

9. The preparation method according to any one of claims 1 to 8, characterized in that: The chemical reaction is carried out in a solvent; preferably, the dielectric constant of the solvent is 2.2-49, preferably 2.6-37.

10. A cyclic polymer, characterized in that The cyclic polymer is prepared by the method for preparing a cyclic polymer according to any one of claims 1 to 9, and preferably, the diameter of the cyclic polymer is 3-100 nm.

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