A method of polymerization of substituted glycolides

Abstract

The application provides a substituted glycolide polymerization method, which comprises the following steps: carrying out polymerization reaction of substituted glycolide under the catalysis of an amino phenol oxy lanthanum complex catalyst. The substituted glycolide has the structure shown in formula (I); and the amino phenol oxy lanthanum complex catalyst has the structure shown in formula (II). Compared with the prior art, the polymerization method provided by the application enables the substituted glycolide to carry out high-activity and high-regioselectivity ring-opening polymerization; when copolymerizing with lactide monomers, the substituted glycolide and lactide one-pot feeding polymerization mode is adopted to obtain random copolymers, and the sequential feeding polymerization mode is adopted to obtain two-block copolymers.

Description

Technical Field

[0001] This invention relates to the field of polymer synthesis technology, and more particularly to a polymerization method for substituted glycolide. Background Technology

[0002] With increasing environmental awareness, people are paying more and more attention to biodegradable materials. Scientists have focused their research on the synthesis technology, process improvement, and performance enhancement of polylactic acid (PLA), and have achieved many results. When lactide is used instead of lactic acid as a monomer, the molecular weight of the polymer obtained by ring-opening polymerization catalyzed by metal complexes is 1 to 3 orders of magnitude higher than that of the polymer obtained by lactic acid condensation polymerization (Adv. Mater., 2000, 12, 1841-1846). However, the glass transition temperature of the obtained PLA materials is usually small and generally low (Tglass transition temperature of random and heterospecific PLA is relatively low). g Polylactic acid (PLA) has a degradation rate of approximately 60°C, making it unsuitable for industrial and consumer products requiring higher temperatures. Its rapid degradation rate also hinders its suitability for durable materials. Furthermore, it cannot be modified after polymerization, failing to meet the diverse application requirements of PLA materials. Therefore, it is necessary to develop new polyester materials with varying properties while also meeting biodegradability requirements. These properties can typically be altered by adjusting the polymer's microstructure. Scientists have synthesized PLA derivatives by modifying the structure of the repeating units themselves and the sequence structure of the interconnections between repeating units, such as using substituted glycolide as a monomer or copolymerizing other lactones (e.g., glycolide) with lactide (Biomacromolecules, 2016, 17, 1383-1394).

[0003] In the polymerization of substituted glycolide, two different α-hydroxy acid units can be introduced into the polymer chain, making the polymerization more efficient, and the regioselectivity of the ring-opening of the two ester functional groups in the monomer is also improved. reg The possibility of ring-opening polymerization from one side also varies greatly, significantly impacting polymer properties. In 2000, Feng's group used stannous octoate (Sn(Oct)2) (J. Polym. Sci.: Part A: Polym. Chem., 2000, 38, 4179-4184) to polymerize D,L-3-methylglycolic acid (rac-MG), P reg Only 0.85. In 2020, Satoh's group polymerized chiral 3-methyl glycolide using phosphazene base (P2-t-Bu), P reg =0.95, the monomer undergoes ring-opening cleavage from the acyl-oxygen bond of the lactic acid structural unit (Polym. Chem., 2020, 11, 6365-6373). In 2021, Coates' group used aluminum complexes of chiral binaphthyl Schiff base ligands to polymerize (S)-methyl glycolide, P reg=0.98, the monomer breaks the acyl-oxygen bond from the glycolic acid structural unit (J. Am. Chem. Soc. 2021, 143, 4119-4124), but the catalytic activity is not high. The above four cases illustrate that factors such as the type of catalyst and chirality affect the regioselectivity of the ring-opening polymerization of substituted glycolide.

[0004] In 2020, Ivchenko's group polymerized (S)-3-isopropyl-substituted glycolide and (S)-3-isobutyl-substituted glycolide, but the organic base TBD did not exhibit good regioselectivity for either monomer (Polym. Chem., 2020, 11, 6890-6902). To date, there are no reports on highly regioselective ring-opening polymerization of these two monomers.

[0005] Lactose can also be copolymerized with other lactone monomers (such as substituted glycolide) to further adjust the properties of polylactic acid, synthesizing materials more suitable for drug sustained release and materials more suitable for post-polymerization modification for biodiagnostics and detection. In 2021, Wu's group used zirconium metal complexes that exhibited high heteroregular selectivity for rac-LA polymerization to catalyze the one-pot copolymerization of L-LA and D-benzyl glycolide, obtaining a poly(knurled) degree of alternation P. alt The copolymer with a ratio of 0.94 (Macromolecules, 2021, 54, 9027-9038) demonstrates that some organometallic complexes exhibit high controllability in certain polymerization reactions.

[0006] In the field of substituted glycolide as a monomer or copolymerization of lactide with substituted glycolide, the catalysts used in some studies are very limited, mainly stannous octoate, which has a simple structure and performance. Therefore, this invention utilizes rare earth complexes with high activity and controllability for the ring-opening polymerization of lactide to catalyze the polymerization of substituted glycolide and copolymerization with lactide, thereby improving traditional polylactic acid in two ways. Summary of the Invention

[0007] The purpose of this invention is to provide a polymerization method for substituted glycolide.

[0008] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0009] This invention provides a polymerization method for substituted glycolide, comprising the following steps:

[0010] The substituted glycolide was polymerized under the catalysis of an aminophenoloxylanthanum complex catalyst.

[0011] The substituted glycolide has the structure shown in formula (I):

[0012]

[0013] In the formula (I):

[0014] R is hydrogen, or a C1-C6 straight-chain, branched, or cyclic alkyl group, C6-C6... 18 aryl, C7~C 20 Mono- or polyaryl-substituted alkyl groups;

[0015] The carbon atom marked with an asterisk (*) has an R-, S-, or racemic configuration.

[0016] The aminophenoloxylanthanum complex catalyst has the structure shown in formula (II):

[0017]

[0018] In formula (II):

[0019] The R 1 ~R 2 Independently selected from hydrogen, C1 to C 12 Alkyl groups with straight, branched, or cyclic structures, C7–C6 20 Mono- or polyaryl-substituted alkyl groups, and one of the halogens.

[0020] Preferably, in formula (I), R is methyl, ethyl, n-propyl, isopropyl, n-butyl, isobutyl, phenyl, or benzyl.

[0021] Preferably, the substituted glycolide has one of the structures shown in formulas (III) to (IV):

[0022]

[0023] Preferably, in formula (II), R 1 ~R 2 It is independently selected from one of methyl, tert-butyl, isopropylphenyl or triphenylmethyl.

[0024] Preferably, the aminophenoloxylanthanum complex catalyst has the structure shown in formula (V):

[0025]

[0026] Preferably, the raw material formulation of the polymerization reaction further includes lactide as a comonomer; the lactide is one or more of L-lactide, D-lactide, meso-lactide or rac-lactide.

[0027] Preferably, the molar ratio of the aminophenoloxylanthanum complex catalyst to the substituted glycolide is 1:(10-10000); the molar ratio of the aminophenoloxylanthanum complex catalyst to lactide is 1:(0-10000).

[0028] Preferably, the polymerization reaction temperature is 0–250°C;

[0029] The polymerization reaction takes 0.001 to 200 hours;

[0030] The polymerization reaction is carried out under an inert atmosphere.

[0031] Preferably, the raw materials for the polymerization reaction further include a solvent; the solvent is one or more of toluene, tetrahydrofuran, dichloromethane, n-hexane, petroleum ether, m-xylene, o-xylene, mesitylene, and trichlorobenzene.

[0032] Preferably, the raw materials for the polymerization reaction further include alcohol compounds;

[0033] The molar ratio of the benzimidazole-substituted aminophenol oxy zinc complex catalyst to the alcohol compound is 1:(0-20).

[0034] Preferably, the alcohol compound is C1-C6. 10 Alkyl alcohols with straight-chain, branched, or cyclic structures, or C7–C666... 20 Alkyl alcohols that are monoaryl-substituted or polyaryl-substituted.

[0035] This invention provides a polymerization method for substituted glycolide, comprising the following steps: polymerizing the substituted glycolide under the catalysis of an aminophenoloxylanthanum complex catalyst. Compared with the prior art, the polymerization method provided by this invention enables the substituted glycolide to undergo highly active and highly regioselective ring-opening polymerization; when copolymerizing with lactide monomers, a random copolymer is obtained when using a one-pot feeding polymerization method, and a diblock copolymer is obtained when using a sequential feeding polymerization method. Detailed Implementation

[0036] This invention provides a polymerization method for substituted glycolide, comprising the following steps:

[0037] The substituted glycolide was polymerized under the catalysis of an aminophenoloxylanthanum complex catalyst.

[0038] The substituted glycolide has the structure shown in formula (I):

[0039]

[0040] In the formula (I):

[0041] R is hydrogen, or a C1-C6 straight-chain, branched, or cyclic alkyl group, C6-C6... 18 aryl, C7~C 20 Mono- or polyaryl-substituted alkyl groups;

[0042] The carbon atom marked with an asterisk (*) has an R-, S-, or racemic configuration.

[0043] The aminophenoloxylanthanum complex catalyst has the structure shown in formula (II):

[0044]

[0045] In formula (II):

[0046] The R 1 ~R 2 Independently selected from hydrogen, C1 to C 12 Alkyl groups with straight, branched, or cyclic structures, C7–C6 20 Mono- or polyaryl-substituted alkyl groups, and one of the halogens;

[0047] In this invention, in formula (I), R is ethyl, n-propyl, isopropyl, n-butyl, isobutyl, phenyl, or benzyl.

[0048] In this invention, the substituted glycolide is most preferably one of the structures shown in formulas (III) to (IV):

[0049]

[0050] For ease of description and understanding, the (S)-3-isopropyl-substituted glycolide shown in formula (III) above is referred to as M1, and the (S)-3-isobutyl-substituted glycolide shown in formula (IV) is referred to as M2.

[0051] In this invention, the preparation method of the substituted glycolide according to formula (I) is as follows:

[0052]

[0053] The substituted α-amino acid was diazotized and hydrolyzed to obtain a substituted α-hydroxy acid, which was then subjected to intermolecular esterification with bromoacetyl bromide, followed by intramolecular esterification to obtain substituted glycolide (I) (Mendeleev Commun., 2018, 28, 61-63; Macromolecules, 2008, 41, 7259-7263).

[0054] In this invention, in formula (II), R 1 ~R 2 It is independently selected from one of methyl, tert-butyl, isopropylphenyl, or triphenylmethyl;

[0055] In this invention, the aminophenoloxylanthanum complex catalyst most preferably has the structure shown in formula (V):

[0056]

[0057] For ease of description and understanding, the aminophenoloxylanthanum complex catalyst with the above structure is now named La1.

[0058] In this invention, the aminophenoloxylanthanum complex catalyst shown in formula (II) can be synthesized with reference to the method reported in the patent (CN202310039418.2).

[0059] In this invention, preferably, the raw materials for the polymerization reaction further include lactide as a comonomer; the lactide is one or more of L-lactide, D-lactide, meso-lactide and rac-lactide, specifically one, two or three.

[0060] The present invention does not have any special requirements on the mixing order of the substituted glycolide, lactide and aminophenoloxylanthanum complex catalyst, and the substituted glycolide, lactide and aminophenoloxylanthanum complex catalyst can be mixed in any order.

[0061] In this invention, the molar ratio of the aminophenoloxylanthanum complex catalyst to the substituted glycolide is preferably 1:(10-10000); more preferably 1:(10-5000); and most preferably 1:(50-500). The molar ratio of the aminophenoloxylanthanum complex catalyst to lactide is preferably 1:(0-10000); more preferably 1:(0-5000); and most preferably 1:(0-1000). This invention does not have special requirements for the molar ratio of the substituted glycolide to lactide, as long as the requirements for the molar ratio of the catalyst to the substituted glycolide and the molar ratio of the catalyst to lactide are met. In this invention, the molar ratio of the substituted glycolide to lactide can be any value.

[0062] In this invention, the preferred temperature for the polymerization reaction is 0–250°C, more preferably 10–200°C, and most preferably 25–100°C. This invention does not impose any special requirements on the heating method for the polymerization reaction; any heating method well-known to those skilled in the art can be used.

[0063] In this invention, the polymerization reaction time is preferably 0.001 to 200 hours, more preferably 0.005 to 50 hours, and most preferably 0.01 to 1 hour.

[0064] In this invention, the polymerization reaction is preferably carried out under an inert atmosphere. This invention does not have any special requirements for the inert atmosphere; any inert atmosphere well known to those skilled in the art can be used, specifically argon.

[0065] In this invention, the raw materials for the polymerization reaction may further include alcohol compounds. In this invention, the alcohol compounds are preferably C1-C64 compounds.10 Alkyl alcohols with straight-chain, branched, or cyclic structures, or C7–C666... 20 Mono- or polyaryl-substituted alkyl alcohols; more preferably C1 to C1. 10 Straight-chain or branched alkyl alcohols, or C7-C6 alkyl alcohols 10 Mono- or polyaryl-substituted alkyl alcohols; most preferably isopropanol and benzyl alcohol. In this invention, the molar ratio of the aminophenoloxylanthanum complex catalyst to the alcohol compound is preferably 1:(0-20), more preferably 1:(0-10), and most preferably 1:(0-5). This invention does not have a special requirement for the order of addition of the alcohol compound; it can be mixed with the substituted glycolide, lactide, and catalyst in any order. In this invention, the alcohol compound is used as a chain transfer agent, which can accelerate the polymerization rate and make the polymer molecular weight closer to the theoretical value, and the molecular weight distribution narrower.

[0066] In this invention, the raw materials for the polymerization reaction preferably also include a solvent, which is preferably one or more of toluene, tetrahydrofuran, dichloromethane, n-hexane, petroleum ether, m-xylene, o-xylene, mesitylene, and trichlorobenzene, specifically one, two, three, four, or five kinds. This invention does not have a special requirement for the order of addition of the solvent; it can be mixed with the alcohol, lactide, substituted glycolide, and catalyst in any order. This invention preferably dissolves the catalyst in the solvent, and preparing a catalyst solvent makes the amount of catalyst added more controllable. In this invention, the amount of solvent added is preferably based on the concentration of the catalyst. In this invention, the molar concentration of the aminophenoloxylanthanum complex catalyst in the solvent is preferably 0.001–0.030 M; more preferably 0.003–0.025 M; and most preferably 0.005–0.010 M.

[0067] This invention does not impose any special requirements on the apparatus used for the polymerization reaction; any apparatus well-known to those skilled in the art that meets the technical requirements of this application may be used. In this invention, the polymerization reaction is preferably carried out in a polymerization flask.

[0068] Preferably, this invention terminates the polymerization reaction by adding a chain terminator after the polymerization time has been reached. This invention does not have specific requirements regarding the type of chain terminator; any chain terminator known to those skilled in the art capable of terminating the polymerization of substituted glycolide can be used. Specifically, commercially available aprotic solvents such as petroleum ether, dichloromethane, n-hexane, and tetrahydrofuran can be employed. This invention does not have specific requirements regarding the amount of the chain terminator; it can be added according to conventional techniques in the art.

[0069] After the reaction is terminated, the present invention preferably uses dichloromethane or other highly polar, low-boiling-point solvents such as chloroform to dissolve the reactants. The present invention does not have special requirements on the amount of dichloromethane used, as long as it is sufficient to completely dissolve all reactants.

[0070] After adding and concentrating the dichloromethane, the present invention preferably adds an alcohol such as methanol, ethanol, isopropanol, or benzyl alcohol to precipitate the polymerization product. The present invention does not have specific requirements on the amount of methanol added, until the precipitate no longer increases.

[0071] After the polymerization product precipitates, the present invention preferably dries the polymerization product at 45°C to obtain the target product. The present invention does not have special requirements for the specific implementation method of the drying; any drying method for solid substances well known to those skilled in the art can be used, specifically vacuum drying (less than 0.1 mmHg). In the present invention, the drying time is preferably 16–28 hours, more preferably 20–26 hours, and most preferably 24 hours.

[0072] This invention provides a polymerization method for substituted glycolide, comprising the following steps: polymerizing the substituted glycolide under the catalysis of an aminophenoloxylanthanum complex catalyst. Compared with the prior art, the polymerization method provided by this invention enables the substituted glycolide to undergo highly regioselective ring-opening polymerization, i.e., preferential ring-opening and cleavage from the acyl-oxygen bond on the less sterically hindered side of the α-carbon substituent; it can also copolymerize with monomers such as lactide, using a one-pot feeding polymerization to obtain random copolymers, and sequential feeding polymerization to obtain diblock copolymers.

[0073] The following detailed description of a method for ring-opening polymerization of substituted glycolide provided by the present invention, with reference to specific embodiments, should not be construed as limiting the scope of protection of the present invention.

[0074] Example 1

[0075] Under argon protection, (S)-3-isopropyl-substituted glycolide (79 mg, 0.5 mmol) was added to a polymerization flask and dissolved in 0.50 mL of toluene. 0.50 mL of a toluene solution of the lanthanum complex catalyst was added to the polymerization flask. [M1]0 = 0.50 M, [La1]0 = 0.01 M, [La1]0:[M1]0 = 1:50. The reaction temperature was controlled at 25 ± 1 °C. After 1.8 minutes, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The mixture was then vacuum dried for 24 h. Calculations and measurements showed a conversion rate >99%. n =1.35×10 4 g / mol, molecular weight distribution

[0076] Example 2

[0077] Under argon protection, (S)-3-isopropyl-substituted glycolide (79 mg, 0.5 mmol) was added to a polymerization flask and dissolved in 0.50 mL of tetrahydrofuran. 0.50 mL of the tetrahydrofuran solution of the lanthanum complex catalyst was added to the polymerization flask. [M1]0 = 0.50 M, [La1]0 = 0.01 M, [La1]0:[M1]0 = 1:50. The reaction temperature was controlled at 25 ± 1 °C. After 3 minutes, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The mixture was then vacuum dried for 24 h. Calculations and measurements showed a conversion rate of 96% and a regioselectivity of P0. reg =0.82. M n =1.21×10 4 g / mol, molecular weight distribution

[0078] Example 3

[0079] Under argon protection, rac-LA (72 mg, 0.5 mmol) and (S)-3-isopropyl-substituted lactide (79 mg, 0.5 mmol) were added to a polymerization flask and dissolved in 0.50 mL of tetrahydrofuran. 0.5 mL of the tetrahydrofuran solution of the lanthanum complex catalyst was added to the polymerization flask. [La1]0 = 0.01 M, [La1]0:[rac-LA]0:[M1]0 = 1:50:50. The reaction temperature was controlled at 25 ± 1 °C. After 4 minutes, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was dried under vacuum for 24 h. Calculations and measurements showed that the conversion rate of rac-LA was 95%, and the conversion rate of M1 was >99%; the lactide repeating units in the polymer were 52%, and the M1 repeating units were 48%; M n =1.88×10 4 g / mol, molecular weight distribution

[0080] Example 4

[0081] Under argon protection, rac-LA (144 mg, 1.0 mmol) and (S)-3-isopropyl-substituted lactide (79 mg, 0.5 mmol) were added to a polymerization flask and dissolved in 0.50 mL of tetrahydrofuran. 0.5 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. [La1]0 = 0.01 M, [La1]0:[rac-LA]0:[M1]0 = 1:100:50. The reaction temperature was controlled at 25 ± 1 °C. After 6 minutes, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of rac-LA was 95%, and the conversion rate of M1 was >99%; the lactide repeating units in the polymer were 66%, and the M1 repeating units were 34%; M n =2.94×10 4 g / mol, molecular weight distribution

[0082] Example 5

[0083] Under argon protection, rac-LA (72 mg, 0.5 mmol) was added to a polymerization flask and dissolved in 0.50 mL of tetrahydrofuran. 0.5 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. After polymerization for 0.7 minutes, (S)-3-isopropyl-substituted glycolide (79 mg, 0.5 mmol) was added to continue the reaction. [La1]0 = 0.01 M, [La1]0:[rac-LA]0:[M1]0 = 1:50:50. The reaction temperature was controlled at 25 ± 1 °C. After 3 minutes of reaction, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of rac-LA was >99%, the conversion rate of M1 was >99%, the percentage of lactide units in the polymer was 52%, and the percentage of M1 units was 48%. n =2.01×10 4 g / mol, molecular weight distribution

[0084] Example 6

[0085] Under argon protection, rac-LA (144 mg, 1.0 mmol) was added to a polymerization flask and dissolved in 0.50 mL of tetrahydrofuran. 0.5 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. After polymerization for 0.8 minutes, (S)-3-isopropyl-substituted glycolide (79 mg, 0.5 mmol) was added to continue the reaction. [La1]0 = 0.01 M, [La1]0:[rac-LA]0:[M1]0 = 1:100:50. The reaction temperature was controlled at 25 ± 1 °C. After 2 minutes of reaction, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of rac-LA was >99%, the conversion rate of M1 was 78%, the percentage of lactide units in the polymer was 71%, and the percentage of M1 units was 29%. n =3.09×10 4 g / mol, molecular weight distribution

[0086] Example 7

[0087] Under argon protection, L-LA (72 mg, 0.5 mmol) and (S)-3-isopropyl-substituted lactide (79 mg, 0.5 mmol) were added to a polymerization flask and dissolved in 0.50 mL of tetrahydrofuran. 0.5 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. [La1]0 = 0.01 M, [La1]0:[L-LA]0:[M1]0 = 1:50:50. The reaction temperature was controlled at 25 ± 1 °C. After 5 minutes, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of L-LA was 79%, and the conversion rate of M1 was 88%; the lactide repeating units in the polymer were 49%, and the M1 repeating units were 51%; M... n =1.92×10 4 g / mol, molecular weight distribution

[0088] Example 8

[0089] Under argon protection, L-LA (144 mg, 1.0 mmol) and (S)-3-isopropyl-substituted lactide (79 mg, 0.5 mmol) were added to a polymerization flask and dissolved in 0.50 mL of tetrahydrofuran. 0.5 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. [La1]0 = 0.01 M, [La1]0:[L-LA]0:[M1]0 = 1:100:50. The reaction temperature was controlled at 25 ± 1 °C. After 5 minutes, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of L-LA was 86%, and the conversion rate of M1 was 92%; the lactide repeating units in the polymer were 66%, and the M1 repeating units were 34%; M... n =3.40×10 4 g / mol, molecular weight distribution

[0090] Example 9

[0091] Under argon protection, L-LA (72 mg, 0.5 mmol) was added to a polymerization flask and dissolved in 0.50 mL of tetrahydrofuran. 0.5 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. After polymerization for 0.5 minutes, (S)-3-isopropyl-substituted glycolide (79 mg, 0.5 mmol) was added to continue the reaction. [La1]0 = 0.01 M, [La1]0:[L-LA]0:[M1]0 = 1:50:50. The reaction temperature was controlled at 25 ± 1 °C. After 2 minutes of reaction, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rates of L-LA and M1 were >99%; the percentage of lactide repeating units in the polymer was 50%, and the percentage of M1 repeating units was 50%. n =2.38×10 4 g / mol, molecular weight distribution

[0092] Example 10

[0093] Under argon protection, L-LA (144 mg, 1.0 mmol) was added to a polymerization flask and dissolved in 0.50 mL of tetrahydrofuran. 0.5 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. After polymerization for 0.7 minutes, (S)-3-isopropyl-substituted glycolide (79 mg, 0.5 mmol) was added to continue the reaction. [La1]0 = 0.01 M, [La1]0:[L-LA]0:[M1]0 = 1:100:50. The reaction temperature was controlled at 25 ± 1 °C. After 2 minutes of reaction, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the L-LA conversion was >99%, the M1 conversion was 80%, the glycolide chain length in the polymer was 71%, and the M1 chain length was 29%. n =3.54×10 4 g / mol, molecular weight distribution

[0094] Example 11

[0095] Under argon protection, (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol) was added to a polymerization flask and dissolved in 0.75 mL of toluene. 0.25 mL of a toluene solution of the lanthanum complex catalyst was added to the polymerization flask. [M2]0 = 1.0 M, [La1]0 = 0.005 M, [La1]0:[M2]0 = 1:200. The reaction temperature was controlled at 25 ± 1 °C. After 1 minute, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The mixture was then vacuum dried for 24 h. Calculations and measurements showed a conversion rate >99%. n =5.25×10 4 g / mol, molecular weight distribution

[0096] Example 12

[0097] Under argon protection, (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol) was added to a polymerization flask and dissolved in 0.75 mL of tetrahydrofuran. 0.25 mL of a tetrahydrofuran solution containing a lanthanum complex catalyst was added to the polymerization flask. [M2]0 = 1.0 M, [La1]0 = 0.005 M, [La1]0:[M2]0 = 1:200. The reaction temperature was controlled at 25 ± 1 °C. After 2.5 minutes, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The product was then vacuum dried for 24 h. Calculations and measurements showed a conversion rate >99%, and a ring-opening regioselectivity of P0. reg =0.88. M n =4.77×10 4g / mol, molecular weight distribution

[0098] Example 13

[0099] Under argon protection, (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol) was added to a polymerization flask and dissolved in 0.90 mL of tetrahydrofuran. 0.10 mL of a tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. [M2]0 = 1.0 M, [La1]0 = 0.002 M, [La1]0:[M2]0 = 1:500. The reaction temperature was controlled at 25 ± 1 °C. After 17 minutes, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The mixture was then vacuum dried for 24 h. Calculations and measurements showed a conversion rate of 22%. n =2.94×10 4 g / mol, molecular weight distribution

[0100] Example 14

[0101] Under argon protection, rac-LA (144 mg, 1.0 mmol) and (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol) were added to a polymerization flask and dissolved in 0.75 mL of tetrahydrofuran. 0.25 mL of a tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. [La1]0 = 0.005 M, [La1]0:[rac-LA]0:[M2]0 = 1:200:200. The reaction temperature was controlled at 25 ± 1 °C. After 1 minute, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of rac-LA was 95%, and the conversion rate of M2 was >99%; the percentage of lactide units in the polymer was 48%, and the percentage of M2 units was 52%. n =5.06×10 4 g / mol, molecular weight distribution

[0102] Example 15

[0103] Under argon protection, rac-LA (101 mg, 0.7 mmol) and (S)-3-isobutyl-substituted glycolide (224 mg, 1.3 mmol) were added to a polymerization flask and dissolved in 0.75 mL of tetrahydrofuran. 0.25 mL of a tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. [La1]0 = 0.005 M, [La1]0:[rac-LA]0:[M2]0 = 1:140:260. The reaction temperature was controlled at 25 ± 1 °C. After 1 minute, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of rac-LA was 90%, and the conversion rate of M2 was >99%; the percentage of lactide units in the polymer was 33%, and the percentage of M2 units was 67%. n =5.35×10 4 g / mol, molecular weight distribution

[0104] Example 16

[0105] Under argon protection, rac-LA (187 mg, 1.3 mmol) and (S)-3-isobutyl-substituted glycolide (120 mg, 0.7 mmol) were added to a polymerization flask and dissolved in 0.75 mL of tetrahydrofuran. 0.25 mL of a tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. [La1]0 = 0.005 M, [La1]0:[rac-LA]0:[M2]0 = 1:260:140. The reaction temperature was controlled at 25 ± 1 °C. After 2 minutes, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of rac-LA was 92%, and the conversion rate of M2 was >99%; the percentage of lactide units in the polymer was 63%, and the percentage of M2 units was 37%. n =5.64×10 4 g / mol, molecular weight distribution

[0106] Example 17

[0107] Under argon protection, rac-LA (245 mg, 1.7 mmol) and (S)-3-isobutyl-substituted glycolide (52 mg, 0.3 mmol) were added to a polymerization flask and dissolved in 0.75 mL of tetrahydrofuran. 0.25 mL of a tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. [La1]0 = 0.005 M, [La1]0:[rac-LA]0:[M2]0 = 1:340:60. The reaction temperature was controlled at 25 ± 1 °C. After 2 minutes, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of rac-LA was 93%, and the conversion rate of M2 was >99%; the percentage of lactide units in the polymer was 83%, and the percentage of M2 units was 17%; M... n =5.09×10 4 g / mol, molecular weight distribution

[0108] Example 18

[0109] Under argon protection, L-LA (144 mg, 1.0 mmol) and (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol) were added to a polymerization flask and dissolved in 0.75 mL of tetrahydrofuran. 0.25 mL of a tetrahydrofuran solution containing the lanthanum complex catalyst was added to the polymerization flask. [La1]0 = 0.005 M, [La1]0:[L-LA]0:[M2]0 = 1:200:200. The reaction temperature was controlled at 25 ± 1 °C. After 1 minute, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rates of L-LA and M2 were >99%; the percentage of lactide units in the polymer was 50%, and the percentage of M2 units was 50%. n =6.21×10 4 g / mol, molecular weight distribution

[0110] Example 19

[0111] Under argon protection, rac-LA (144 mg, 1.0 mmol) was added to a polymerization flask and dissolved in 0.75 mL of tetrahydrofuran. 0.25 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added sequentially to the polymerization flask. After polymerization for 0.7 minutes, (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol) was added to continue the reaction. [La1]0 = 0.005 M, [La1]0:[rac-LA]0:[M2]0 = 1:200:200. The reaction temperature was controlled at 25 ± 1 °C. After 1 minute of reaction, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of rac-LA was >99%, the conversion rate of M2 was >99%, the percentage of lactide units in the polymer was 50%, and the percentage of M2 units was 50%. n =4.13×10 4 g / mol, molecular weight distribution

[0112] Example 20

[0113] Under argon protection, L-LA (144 mg, 1.0 mmol) was added to a polymerization flask and dissolved in 0.75 mL of tetrahydrofuran. 0.25 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added sequentially to the polymerization flask. After polymerization for 1 minute, (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol) was added to continue the reaction. [La1]0 = 0.005 M, [La1]0:[L-LA]0:[M2]0 = 1:200:200. The reaction temperature was controlled at 25 ± 1 °C. After 0.8 minutes, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of L-LA was >99%, the conversion rate of M2 was >99%, the percentage of lactide units in the polymer was 49%, and the percentage of M2 units was 51%. n =6.24×10 4 g / mol, molecular weight distribution

[0114] Example 21

[0115] Under argon protection, L-LA (144 mg, 1.0 mmol) was added to a polymerization flask and dissolved in 0.75 mL of tetrahydrofuran. 0.25 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added sequentially to the polymerization flask. After polymerization for 0.8 minutes, (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol) was added to continue the reaction. [La1]0 = 0.005 M, [La1]0:[L-LA]0:[M2]0 = 1:200:200. The reaction temperature was controlled at 25 ± 1 °C. After 1.5 minutes of reaction, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of L-LA was >99%, the conversion rate of M2 was >99%, the percentage of lactide repeating units in the polymer was 50%, and the percentage of M2 repeating units was 50%. n =5.36×10 4 g / mol, molecular weight distribution

[0116] Example 22

[0117] Under argon protection, rac-LA (288 mg, 2.0 mmol) was added to a polymerization flask and dissolved in 0.75 mL of tetrahydrofuran. 0.25 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added sequentially to the polymerization flask. After polymerization for 1.3 minutes, (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol) was added to continue the reaction. [La1]0 = 0.005 M, [La1]0:[rac-LA]0:[M2]0 = 1:400:200. The reaction temperature was controlled at 25 ± 1 °C. After 2 minutes of reaction, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of rac-LA was >99%, the conversion rate of M2 was >99%, the percentage of lactide units in the polymer was 67%, and the percentage of M2 units was 33%. n =6.34×10 4 g / mol, molecular weight distribution

[0118] Example 23

[0119] Under argon protection, L-LA (288 mg, 2.0 mmol) was added to a polymerization flask and dissolved in 0.75 mL of tetrahydrofuran. 0.25 mL of the tetrahydrofuran solution containing the lanthanum complex catalyst was added sequentially to the polymerization flask. After polymerization for 1 minute, (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol) was added to continue the reaction. [La1]0 = 0.005 M, [La1]0:[L-LA]0:[M2]0 = 1:400:200. The reaction temperature was controlled at 25 ± 1 °C. After 2 minutes of reaction, petroleum ether was added to terminate the reaction. The solvent was removed, and the residue was dissolved in dichloromethane. The polymer was washed with methanol. The polymer was then vacuum dried for 24 h. Calculations and measurements showed that the conversion rate of L-LA was >99%, the conversion rate of M2 was >99%, the percentage of lactide units in the polymer was 67%, and the percentage of M2 units was 33%. n =8.89×10 4 g / mol, molecular weight distribution

[0120] Example 24

[0121] Under argon protection, (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol) was added to a polymerization flask, followed by 0.10 mL of a toluene solution of catalyst La1. The [La1]0:[M2]0 ratio was maintained at 1:500. The mixture was stirred in an oil bath at 110 ± 1°C for 1 minute, and then petroleum ether was added to terminate the polymerization. The solvent was removed, and the residue was dissolved in dichloromethane and washed with methanol. The polymer was then vacuum dried for 24 h. The monomer conversion was >99% based on 1H and 1C NMR spectroscopy and calculations; the ring-opening regioselectivity was P0. reg =0.73. M was measured by GPC. n =8.91×10 4 g / mol, molecular weight distribution

[0122] Example 25

[0123] Under argon protection, (S)-3-isobutyl-substituted glycolide (172 mg, 1.0 mmol), 0.10 mL of a toluene solution of catalyst La1, and a toluene solution of benzyl alcohol were added to a polymerization flask. The [La1]0:[BnOH]0:[M2]0 ratio was maintained at 1:1:200. The mixture was stirred in a 25±1°C oil bath for 0.5 minutes, and the polymerization was terminated by adding petroleum ether. The solvent was removed, and the residue was dissolved in dichloromethane and washed with methanol. The polymer was then vacuum dried for 24 h. The monomer conversion was >99% based on 1H NMR and 1C NMR spectroscopy, and the regioselectivity was P0. reg =0.85. M was measured by GPC. n =4.71×10 4 g / mol, molecular weight distribution

[0124]

[0125] As can be seen from the above embodiments, the present invention provides a polymerization method for substituted glycolide, comprising the following steps: polymerizing the substituted glycolide under the catalysis of an aminophenoloxylanthanum complex catalyst. Compared with the prior art, the polymerization method provided by the present invention enables the substituted glycolide to undergo highly regioselective ring-opening polymerization, preferentially breaking the ring at the acyl-oxygen bond on the less sterically hindered side of the α-carbon substituent; it can also copolymerize with monomers such as lactide, using a one-pot feeding polymerization to obtain random copolymers, and sequential feeding polymerization to obtain diblock copolymers.

[0126] The above description is only a preferred embodiment of the present invention. It should be noted that for those skilled in the art, several improvements and modifications can be made without departing from the principle of the present invention, and these improvements and modifications should also be considered within the scope of protection of the present invention.

Claims

1. A polymerization method for substituted glycolide, comprising the following steps: The substituted glycolide was polymerized under the catalysis of an aminophenoloxylanthanum complex catalyst. The substituted glycolide has the structure shown in formula (I): In the formula (I): R is n-propyl, isopropyl, n-butyl, isobutyl, phenyl, or benzyl. The carbon atom marked with an asterisk (*) has an R-, S-, or racemic configuration. The aminophenoloxylanthanum complex catalyst has the structure shown in formula (II): In formula (II): The R 1 ~R 2 Independently selected from hydrogen, C1 to C 12 Alkyl groups with straight, branched, or cyclic structures, C7–C6 20 Mono- or polyaryl-substituted alkyl groups, and one of the halogens.

2. The polymerization method according to claim 1, characterized in that, The substituted glycolide has one of the structures shown in formulas (III) to (IV):

3. The polymerization method according to claim 1, characterized in that, In formula (II), R 1 ~R 2 It is independently selected from one of methyl, tert-butyl, isopropylphenyl or triphenylmethyl.

4. The polymerization method according to claim 1, characterized in that, The aminophenoloxylanthanum complex catalyst has the structure shown in formula (V):

5. The polymerization method according to claim 1, characterized in that, The raw materials for the polymerization reaction also include lactide as a comonomer; the lactide is one or more of L-lactide, D-lactide, meso-lactide or rac-lactide.

6. The polymerization method according to claim 1, characterized in that, The molar ratio of the aminophenoloxylanthanum complex catalyst to the substituted glycolide is 1:(10-10000); the molar ratio of the aminophenoloxylanthanum complex catalyst to lactide is 1:(0-10000).

7. The polymerization method according to claim 1, characterized in that, The polymerization reaction is carried out at a temperature of 0–250°C and for a duration of 0.001–200 hours.

8. The polymerization method according to claim 1, characterized in that, The raw materials for the polymerization reaction also include a solvent; the solvent is one or more of toluene, tetrahydrofuran, dichloromethane, n-hexane, petroleum ether, m-xylene, o-xylene, mesitylene, and trichlorobenzene.

9. The polymerization method according to claim 1, characterized in that, The raw materials for the polymerization reaction also include alcohol compounds; the alcohol compounds are C1 to C2. 10 Alkyl alcohols with straight-chain, branched, or cyclic structures, or C7–C666... 20 Mono- or polyaryl-substituted alkyl alcohols; the molar ratio of the aminophenoloxylanthanum complex catalyst to the alcohol compound is 1:(0-20).

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