A method of synthesizing a functionalized polyether in a multi-proton system

Abstract

The application discloses a method for synthesizing functional polyether in a multi-proton system, which comprises the following steps: mixing an epoxy monomer, an amino alcohol / acid compound, an organic base and an alkyl boron to perform a polymerization reaction, so as to obtain a urethane / amide / short peptide functional polyether. The application utilizes the acidic inversion phenomenon of NH-type proton groups and hydroxyl groups in a two-component organic catalytic system, so that the hydroxyl groups are preferentially activated in the multi-proton system, thereby enabling the polymerization reaction to be performed only at the hydroxyl / carboxyl end, and finally, the urethane / amide / short peptide functional polyether with controllable molecular weight and definite end group structure can be site-selectively synthesized through one-step reaction. The method is simple, efficient and controllable, and is suitable for large-scale industrial application.

Description

Technical Field

[0001] This invention relates to the field of polymer synthesis technology, and more specifically to a method for synthesizing functionalized polyethers in a multiproton system. Background Technology

[0002] Functional groups can not only enrich or improve the mechanical, thermal, optical, electrical, crystallization, rheological, mechanical, solution, interfacial, and biocompatibility properties of polymer materials, but also enable polymers to acquire specific chemical reactivity for structural and property evolution, or couple with the surfaces of other small molecules, polymers, biomacromolecules, solids, or micro / nano particles to construct complex drug or material systems. Therefore, the quantitative and site-specific introduction of functional groups into polymer structures is one of the key focuses of polymer synthesis research.

[0003] As is well known, placing target functional groups or precursor functional groups in the initiator structure of chain polymerization is an effective method for site-specific functionalization at the ends or centers of polymer chains. This method integrates polymer synthesis and functionalization, offering significant step economy and modularity, making it highly scalable. It can yield functionalized polymers with diverse structures and properties without altering existing synthetic routes, processes, and equipment. However, the stringent reaction conditions required for polymerization often lead to incompatibility between the functionalizing initiator and the functional groups located at the initiator or polymer chain initiation ends. The latter may interact or react with monomers, catalysts, or the active ends of chain growth, resulting in polymerization deactivation or runaway, ultimately failing to obtain the target polymer structure.

[0004] Currently, aliphatic polyethers, represented by polyethylene oxide (PEO / PEG) and polypropylene oxide (PPO), are produced in large quantities and have extremely wide applications. The end groups are a key factor determining their performance. Anionic ring-opening polymerization of epoxy monomers is a common method for synthesizing aliphatic polyethers. However, highly reactive functional groups, especially electrophilic and proton functional groups, are often difficult to maintain stably during anionic ring-opening polymerization. Therefore, an indirect method is needed to first introduce less reactive functional groups compatible with ring-opening polymerization, and then introduce the target functional group through a coupling reaction. This process often introduces additional atoms or groups as links, ultimately affecting the product's performance. In recent years, with the continuous development of catalytic and initiation systems for anionic ring-opening polymerization, the chemoselectivity and functional group tolerance of this type of polymerization reaction have been significantly improved. Functionalized initiators can be used to directly introduce some reactive functional groups or precursor groups that are easily converted (deprotected) into the target functional group, greatly improving the synthesis efficiency and accuracy of functionalized polyethers. However, currently used functionalized initiators are limited to (thio)carboxylic acids or monoprotic compounds containing hydroxyl (OH) and electrophilic functional groups (e.g., carbon-carbon double bonds, carboxylic acid esters). It remains unknown whether initiators containing multiple protic functional groups can selectively initiate the one-step conversion into structurally controllable functionalized polyethers.

[0005] Multiprotic compounds (e.g., amino acid compounds, amino alcohol compounds) are widely found in biomass raw materials. If these compounds can be introduced into polymer structures as functional groups in a controllable manner, it will greatly enrich or enhance the physical, chemical and biological properties of polymer materials. However, in addition to classic initiating groups (e.g., hydroxyl, carboxyl), these compounds also contain proton groups such as urethane (amino protecting group) and amides. The acidity of these NH-type proton groups is higher than that of the OH at the end of the growing chain during the ring-opening polymerization of epoxy monomers. In classic anionic ring-opening polymerization systems based on strong basic catalysts or initiators, the NH-type proton groups are preferentially activated (deprotonated), and the resulting urethane or amide anions become chain initiating species to participate in the polymerization reaction (Hassouna, L.; Illy, N.; Guégan, P, Phosphazene / triisobutylaluminum-Promoted Anionic Ring-opening Polymerization of 1,2-Epoxybutane Initiated By Secondary Carbamates, Polymer Chemistry 2017, 8, 4005-4013). This is also a common problem in multi-proton ring-opening polymerization systems.

[0006] Studies have shown that utilizing the non-covalent interaction formed in situ between amino groups and alkylboron to reduce the activity of amino groups and stabilize them in the anionic ring-opening polymerization process of epoxy monomers allows the reaction to occur only at the hydroxyl end, ultimately enabling the one-step synthesis of amino-functionalized polyethers (Chen, Y.; Zhao, J.; et al., Noncovalent Protection for Direct Synthesis of α-Amino-ω-Hydroxyl Poly(ethylene oxide), ACS Macro Lett. 2021, 10, 737-743; CN 110437435 A A One-Step Synthesis Method for Terminally Amino-Functionalized Polyethers). However, this non-covalent interaction is relatively weak, and the protection of the amino group is easily compromised, limiting the product stability and flexibility of post-processing (e.g., difficulty in selectively modifying the hydroxyl end of the polymer). Furthermore, when the target polymer has a small molecular weight, the non-covalent protection method requires the use of large amounts of toxic and flammable alkylboron, resulting in high costs and significant safety risks, making it difficult to meet practical application requirements.

[0007] Therefore, developing a controllable synthesis method for functionalized polyethers suitable for multiprotic systems is of great significance. Summary of the Invention

[0008] The purpose of this invention is to provide a method for synthesizing functionalized polyethers in a multiprotic system.

[0009] The technical solution adopted in this invention is:

[0010] A method for synthesizing functionalized polyethers in a multiprotic system includes the following steps: mixing an epoxy monomer, an amino alcohol / acid compound, an organic base, and an alkyl boron to carry out a polymerization reaction to obtain a urethane / amide / short peptide functionalized polyether.

[0011] Preferably, the molar ratio of the epoxy monomer, amino alcohol / acid compound, organic base, and alkyl boron is 1-1000:1:0.01-3:0.01-5.

[0012] More preferably, the molar ratio of the epoxy monomer, amino alcohol / acid compound, organic base, and alkyl boron is 40-120:1:0.02-0.1:0.05-0.5.

[0013] Preferably, the molar ratio of the organic base to the alkyl boron is 0.2 to 5:1.

[0014] More preferably, the molar ratio of the organic base to the alkyl boron is 0.2 to 0.5:1.

[0015] Preferably, the epoxy monomer is ethylene oxide, C1-C64. 20Straight-chain alkyl-substituted ethylene oxide, styrene oxide, cyclohexane oxide, 4-vinylcyclohexane oxide, limonene oxide, C1-C 16 At least one of the following: linear alkyl glycidyl ether, isopropyl glycidyl ether, tert-butyl glycidyl ether, 2-ethylhexyl glycidyl ether, phenyl glycidyl ether, benzyl glycidyl ether, allyl glycidyl ether, propargyl glycidyl ether, and glycidyl methacrylate, with the following structural formula:

[0016]

[0017] More preferably, the epoxy monomer is at least one of ethylene oxide and propylene oxide.

[0018] Preferably, the amino alcohol compound has the following structural formula: In the formula, R0 is tert-butyl or benzyl, and R1 is hydrogen, methyl, isopropyl, tert-butyl, sec-butyl, n-butyl, ... One of phenyl, hydroxymethyl, and hydroxyethyl, where R2 is methyl, vinyl, or... One of the phenyl groups, where n is an integer from 1 to 9.

[0019] More preferably, the amino alcohol compound is at least one selected from Boc-alkyl alcoholamine, Boc-D-aminopropanol, Boc-D-valine, Boc-L-valine, Boc-L-tert-leucine, Boc-L-isoleucine, Boc-L-neu-leucine, Boc-L-methionine, Boc-L-phenylpropanine, Boc-serine, Boc-D-threonine, Boc-4-hydroxyaniline, Boc-4-aminobenzyl alcohol, Boc-2-(4-aminophenyl)ethanol, N-acetylethanolamine, N-(2-hydroxyethyl)acrylamide, N,N'-bis(2-hydroxyethyl)oxalamide, and N-(2-hydroxyethyl)benzamide.

[0020] Preferably, the alkyl group in the Boc-alkylolamine has 2 to 10 carbon atoms.

[0021] Preferably, the amino acid compound is One of the short peptides protected by the Boc / Cbz group, wherein R0 is tert-butyl or benzyl, and R3 is hydrogen, methyl, isopropyl, sec-butyl, 2-methylbutyl, etc. One of benzyl, phenethyl, p-hydroxybenzyl, hydroxymethyl, hydroxyethyl, 2-hydroxypropyl, carboxymethyl, and carboxyethyl, where n is an integer from 1 to 9.

[0022] More preferably, the amino acid compound is Boc-(4-aminophenyl)carboxylic acid, Boc-(4-aminophenyl)acetic acid, Boc-(4-aminophenyl)propionic acid, Boc-glycine, Cbz-L-glycine, Boc-L-alanine, Cbz-L-alanine, Boc-L-valine, Cbz-L-valine, Boc-L-isoleucine, Cbz-L-isoleucine, or Boc-L-histidine. Cbz-L-histidine, Boc-L-tryptophan, Cbz-L-tryptophan, Boc-L-phenylalanine, Cbz-L-phenylalanine, Boc-L-homophenylalanine, Cbz-L-homophenylalanine, Boc-L-tyrosine, Cbz-L-tyrosine, Boc-L-serine, Cbz-L-serine, Boc-L-homoserine, Cbz-L-homoserine, Cbz-L-threonine, Boc At least one of the following: -L-threonine, Boc-L-aspartic acid, Cbz-L-aspartic acid, Boc-L-glutamic acid, Cbz-L-glutamic acid, Cbz-glycine-proline, Cbz-alanine-proline, Cbz-tryptophan-tryptophan, N-Boc-N'-Cbz-L-lysine, Boc-glycine-glycine, Boc-glycine-leucine, Boc-glycine-proline, Boc-phenylalanine-glycine, Boc-alanine-glycine, Boc-alanine-proline, Boc-leucine-leucine, Boc-leucine-glycine, Boc-valine-valine, Boc-valine-glycine, Boc-valine-alanine, Boc-valine-proline, Boc-glycine-glycine-glycine, Boc-leucine-valine-valine, and Boc-valine-glycine-phenylalanine.

[0023] The structural formulas of some amino alcohols / acids are as follows:

[0024]

[0025] Preferably, the organic base is at least one selected from tertiary amines, amidines, guanidines, triaminophosphine, phosphazene bases, lithium / sodium / potassium / cesium tert-butoxide, lithium / sodium / potassium / cesium / ammonium tert-valerate, thiourea, urea, and carbamates.

[0026] More preferably, the organic base is DABCO, PMDETA, ME6TREN, sparteine, DBN, DBU, MTBD, TMG, PMG, HMTP, HETP, TMAP, TIPAP, BEMP, t BuP1、 t BuP2, EtP2 tAt least one of BuP4, lithium tert-butoxide / sodium / potassium / cesium, lithium pivalate / sodium / potassium / cesium / ammonium, thiourea, urea, and carbamate, with the following structural formula:

[0027]

[0028] Preferably, the alkylborane is β-isopinepine-9-boronbicyclo[3.3.1]nonane (S-Alphine-Borane) or trisec-butylborane (T s BuB), triisopropylborane (T) i At least one of PrB, trimethylborane (TMB), and tris(C2-C8 straight-chain alkyl)borane (TAB), with the following structural formula:

[0029]

[0030] Preferably, the polymerization reaction is carried out at a temperature of 0℃ to 60℃ for a reaction time of 1h to 48h.

[0031] More preferably, the polymerization reaction is carried out at room temperature (25℃±5℃) for 2h to 10h.

[0032] Preferably, the polymerization reaction is carried out in a solvent system, and the solvent is at least one selected from benzene, toluene, tetrahydrofuran, 2-methyltetrahydrofuran, n-hexane, cyclohexane, acetone, ethyl acetate, and tert-butanol.

[0033] Preferably, the initial concentration of the epoxy monomer in the polymerization reaction system is 3 mol / L to 15 mol / L.

[0034] Preferably, the polymerization reaction is carried out in a protective atmosphere.

[0035] Preferably, the protective atmosphere is a nitrogen atmosphere or an argon atmosphere.

[0036] The beneficial effects of this invention are as follows: This invention utilizes the acid inversion phenomenon between NH-type proton groups and hydroxyl groups in a two-component organic catalytic system, so that hydroxyl groups are preferentially activated in a multi-proton system, thereby causing the polymerization reaction to occur only at the hydroxyl / carboxyl ends. Finally, through a one-step reaction, urethane / amide / short peptide functionalized polyethers with controllable molecular weight and well-defined end-group structures can be synthesized site-selectively. This method is simple, efficient, and controllable, and is suitable for large-scale industrial applications.

[0037] Specifically:

[0038] 1) The method for synthesizing functionalized polyethers of the present invention ingeniously utilizes the synergistic mechanism of organic Lewis acid-base pair catalyst (organic base + alkyl boron) in a multiprotic system to achieve acidity reversal between NH type proton groups (urethane, amide, etc.) and OH groups, so that the epoxy monomer reacts only with OH or COOH, realizing site-selective initiation (in conventional anionic ring-opening polymerization under strong basic conditions, NH type proton groups are preferentially activated and can undergo chain transfer to OH after initiation, thus site-selective initiation cannot be achieved). This method is simple, efficient, and controllable to synthesize functionalized polyethers in one step, and has significant step economy compared with the post-polymerization modification method.

[0039] 2) Compared with the non-covalent amino protection strategy, the method of synthesizing functionalized polyethers of the present invention requires a lower amount of catalyst and the protecting group is more stable. The polymer purification process will not cause deprotection. Therefore, the amino terminus can be selectively modified by commonly used Boc group (tert-butyloxycarbonyl) and / or Cbz group (benzyloxycarbonyl), and the amino group can be released by simple deprotection treatment.

[0040] 3) When the method for synthesizing functionalized polyethers of the present invention is applied to the synthesis of amino-functionalized polyethers, the synthesis route is greatly simplified compared with the post-modification method of dihydroxy polyethers, the purity and yield of the product are greatly improved, and the product can be obtained without separation methods such as chromatographic separation and ion exchange resin separation, which is suitable for large-scale and batch production.

[0041] 4) The initiator used in the method for synthesizing functionalized polyethers of the present invention is an amino alcohol / amino acid compound, most of which have biomass-derived properties (renewable), and are inexpensive, readily available, highly commercialized, and extremely diverse in structure. Their use in synthesizing functionalized polymers meets the requirements of green and sustainable development.

[0042] 5) The method for synthesizing functionalized polyethers in this invention uses an initiator and a catalyst that are independent components, and the catalyst does not react directly with the monomer, which facilitates precise end-group control of the polyether to obtain a single-structure product.

[0043] 6) The functionalized polyethers obtained by the method of synthesizing functionalized polyethers of the present invention have no heavy metal residues and are more suitable for application in high-tech industries such as biomedicine and microelectronics. Attached Figure Description

[0044] Figure 1 This is a SEC diagram of the functionalized polyether in Example 11.

[0045] Figure 2 The functionalized polyether in Example 11 1 H NMR spectrum.

[0046] Figure 3 The MALDI-TOF MS curves of the functionalized polyether in Example 11 are shown.

[0047] Figure 4 This is a SEC diagram of the functionalized polyether in Example 12.

[0048] Figure 5 The functionalized polyether in Example 12 1 H NMR spectrum.

[0049] Figure 6 The MALDI-TOF MS curves of the functionalized polyether in Example 12 are shown. Detailed Implementation

[0050] The present invention will be further explained and described below with reference to specific embodiments.

[0051] Conversion rate of epoxy monomers and structural characteristics of polymers: These were determined using a Bruker AV400 liquid nuclear magnetic resonance spectrometer. 1 The results were obtained by HNMR, with the solvent being deuterated chloroform or dimethyl sulfoxide (DMSO).

[0052] Molecular weight and dispersion of polyether: determined using an Agilent 1260 Infinity volume exclusion chromatograph, with tetrahydrofuran (THF) as the mobile phase, column temperature at 35℃, and flow rate at 1 mL / min; calibration curves were prepared using a series of polystyrene (PS) or polyethylene oxide (PEG) standard samples.

[0053] Example 1:

[0054] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0055] In a nitrogen atmosphere, 1.3 mmol of Boc-aminoethanol (BocEA) and 0.0325 mmol of phosphazene base were added. t BuP2, 0.13 mmol of triethylboron, and 3 mL of tetrahydrofuran (THF) were sequentially added to a dry glass reactor and stirred until homogeneous. The glass reactor was then connected to a vacuum line to purge some of the gas inside. The reactor was then cooled using an ice-water bath. 58.5 mmol of ethylene oxide (EO, [EO]0 = 10 mol / L) was added at -20 °C. The glass reactor was sealed and reacted at room temperature for 3 h. The reactor was then opened, chloroform was added, and then diethyl ether was poured in for precipitation. The precipitate was collected and dried under vacuum to obtain the functionalized polyether (urethane functionalized).

[0056] THF, BocEA, and EO are all purified and dehydrated before use.

[0057] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feed ratio of EO to BocEA. n,th It is 2.0 kg / mol.

[0058] Using a series of PEG standard samples as calibration curves, the molecular weight of the functionalized polyether was determined to be 1.7 kg / mol and the dispersion to be 1.07 by SEC (volume exclusion chromatography).

[0059] 1 The monomer conversion rate was 100% as determined by H NMR.

[0060] 1 Characterization by 1H NMR and matrix-assisted laser desorption / ionization time-of-flight mass spectrometry (MALDI-TOF MS) fully demonstrates that the product structure is well-defined.

[0061] Acid desorption protection of functionalized polyether (urethane functionalization): 0.5 g of functionalized polyether, 0.8 mL of trifluoroacetic acid and 2 mL of dichloromethane were added to a sealed glass reactor and reacted at room temperature for 2 h. The reaction solution was then poured into diethyl ether for precipitation. The precipitate was collected and dried under vacuum to obtain amino-functionalized polyether.

[0062] 1 The degree of amino functionalization was determined by H NMR to be 100%, and the molecular weight of the amino-functionalized polyether was determined by SEC to be 1.7 kg / mol and the dispersion was 1.07.

[0063] Example 2:

[0064] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0065] In a nitrogen atmosphere, 104 mmol of propylene oxide (PO), 1.3 mmol of Boc-aminoethanol (BocEA), and 0.0325 mmol of phosphazene base were added. t BuP2 and 0.13 mmol of triethylboron were added sequentially to a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain functionalized polyether (urethane functionalized).

[0066] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feeding ratio of PO to BocEA. n,th It is 4.6 kg / mol.

[0067] Using a series of PS standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 5.5 kg / mol and the dispersion to be 1.06.

[0068] 11H NMR characterization showed that the product had a clear structure and the degree of carbamate functionalization was 98%.

[0069] Example 3:

[0070] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0071] In a nitrogen atmosphere, 1.3 mmol of Boc-aminoethanol (BocEA) and 0.0325 mmol of phosphazene base were added. t BuP2, 0.13 mmol of triethylboron, and 3 mL of toluene were added sequentially to a dry glass reactor and stirred until homogeneous. The glass reactor was then connected to a vacuum line to purge some of the gas inside. The reactor was cooled using an ice-water bath, and then 58.5 mmol of ethylene oxide (EO, [EO]0 = 10 mol / L) was added at -20°C. The glass reactor was sealed and reacted at room temperature for 3 hours. The glass reactor was then opened, chloroform was added, and then diethyl ether was poured in for precipitation. The precipitate was collected and dried under vacuum to obtain the functionalized polyether (urethane functionalized).

[0072] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feed ratio of EO to BocEA. n,th It is 2.0 kg / mol.

[0073] Using a series of PEG standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 2.1 kg / mol and the dispersion to be 1.06.

[0074] 1 1H NMR characterization showed that the product structure was well-defined and the degree of carbamate functionalization was 99%.

[0075] Example 4:

[0076] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0077] In a nitrogen atmosphere, 1.3 mmol of Boc-aminoethanol (BocEA) and 0.0325 mmol of phosphazene base were added. t BuP2, 0.13 mmol of triisopropylborane (T iPrB and 3 mL of tetrahydrofuran (THF) were added sequentially to a dry glass reactor and stirred until homogeneous. The glass reactor was then connected to a vacuum line to purge some of the gas inside. The reactor was cooled using an ice-water bath, and then 58.5 mmol of ethylene oxide (EO, [EO]0 = 10 mol / L) was added at -20 °C. The glass reactor was sealed and reacted at room temperature for 4 h. The glass reactor was then opened, chloroform was added, and then diethyl ether was poured in to precipitate the product. The precipitate was collected and dried under vacuum to obtain the functionalized polyether (urethane functionalized).

[0078] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feed ratio of EO to BocEA. n,th It is 2.0 kg / mol.

[0079] Using a series of PEG standard samples as calibration curves, SEC determined that the molecular weight of the functionalized polyether was 1.8 kg / mol and the dispersion was 1.06.

[0080] 1 1H NMR characterization showed that the product structure was well-defined and the degree of carbamate functionalization was 96%.

[0081] Example 5:

[0082] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0083] In a nitrogen atmosphere, 1.3 mmol of Boc-aminoethanol (BocEA), 0.0325 mmol of triethylenediamine (DABCO), 0.13 mmol of triethylboron, and 3 mL of tetrahydrofuran (THF) were sequentially added to a dry glass reactor and stirred until homogeneous. The glass reactor was then connected to a vacuum line to purge some of the gas inside the reactor and cooled using an ice-water bath. 58.5 mmol of ethylene oxide (EO, [EO]0 = 10 mol / L) was then added at -20 °C. The glass reactor was sealed and reacted at room temperature for 6 h. The glass reactor was then opened, chloroform was added, and then diethyl ether was poured in to precipitate the product. The precipitate was collected and dried under vacuum to obtain the functionalized polyether (urethane functionalization).

[0084] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feed ratio of EO to BocEA. n,th It is 2.0 kg / mol.

[0085] Using a series of PEG standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 2.0 kg / mol and the dispersion to be 1.07.

[0086] 11H NMR characterization showed that the product had a clear structure and the degree of carbamate functionalization was 97%.

[0087] Example 6:

[0088] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0089] In a nitrogen atmosphere, 0.25 mmol of Boc-4-aminobenzyl alcohol (BocBA) and 0.00625 mmol of phosphazene base were added. t BuP2, 0.025 mmol of triethylboron, and 3 mL of tetrahydrofuran (THF) were sequentially added to a dry glass reactor and stirred until homogeneous. The glass reactor was then connected to a vacuum line to purge some of the gas inside. The reactor was cooled using an ice-water bath, and then 27.5 mmol of ethylene oxide (EO, [EO]0 = 10 mol / L) was added at -20°C. The glass reactor was sealed and reacted at room temperature for 3 hours. The glass reactor was then opened, chloroform was added, and then diethyl ether was poured in for precipitation. The precipitate was collected and dried under vacuum to obtain the functionalized polyether (urethane functionalized).

[0090] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feeding ratio of EO to BocBA. n,th It is 4.8 kg / mol.

[0091] Using a series of PEG standard samples as calibration curves, SEC determined that the molecular weight of the functionalized polyether was 5.2 kg / mol and the dispersion was 1.05.

[0092] 1 1H NMR characterization showed that the product structure was well-defined and the degree of carbamate functionalization was 100%.

[0093] Example 7:

[0094] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0095] In a nitrogen atmosphere, 0.25 mmol of Boc-serine alcohol (BocSr) and 0.00625 mmol of phosphazene base were added. tBuP2, 0.025 mmol of triethylboron, and 3 mL of tetrahydrofuran (THF) were sequentially added to a dry glass reactor and stirred until homogeneous. The glass reactor was then connected to a vacuum line to purge some of the gas inside. The reactor was cooled using an ice-water bath, and then 27.5 mmol of ethylene oxide (EO, [EO]0 = 10 mol / L) was added at -20°C. The glass reactor was sealed and reacted at room temperature for 3 hours. The glass reactor was then opened, chloroform was added, and then diethyl ether was poured in for precipitation. The precipitate was collected and dried under vacuum to obtain the functionalized polyether (urethane functionalized).

[0096] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feed ratio of EO to BocSr. n,th It is 4.8 kg / mol.

[0097] Using a series of PEG standard samples as calibration curves, SEC determined that the molecular weight of the functionalized polyether was 4.6 kg / mol and the dispersion was 1.04.

[0098] 1 1H NMR characterization showed that the product had a clear structure and the degree of carbamate functionalization was 98%.

[0099] Example 8:

[0100] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0101] In a nitrogen atmosphere, 0.25 mmol of Boc-valine (BocVV) and 0.00625 mmol of phosphazene base were added. t BuP2, 0.025 mmol of triethylboron, and 3 mL of tetrahydrofuran (THF) were sequentially added to a dry glass reactor and stirred until homogeneous. The glass reactor was then connected to a vacuum line to purge some of the gas inside. The reactor was cooled using an ice-water bath, and then 27.5 mmol of ethylene oxide (EO, [EO]0 = 10 mol / L) was added at -20°C. The glass reactor was sealed and reacted at room temperature for 3 hours. The glass reactor was then opened, chloroform was added, and then diethyl ether was poured in for precipitation. The precipitate was collected and dried under vacuum to obtain the functionalized polyether (Boc-short peptide functionalization).

[0102] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feed ratio of EO to BocVV. n,th It is 4.8 kg / mol.

[0103] Using a series of PEG standard samples as calibration curves, SEC determined that the molecular weight of the functionalized polyether was 5.0 kg / mol and the dispersion was 1.05.

[0104] 1 1H NMR characterization showed that the product structure was well-defined, and the functionalization degree of the Boc-short peptide was 99%.

[0105] Example 9:

[0106] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0107] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Boc-L-valine (BocVal), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially to a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain functionalized polyether (Boc-short peptide functionalization).

[0108] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feed ratio of PO to BocVal. n,th It is 4.6 kg / mol.

[0109] Using a series of PS standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 8.5 kg / mol and the dispersion to be 1.05.

[0110] 1 1H NMR characterization showed that the product structure was well-defined, and the functionalization degree of the Boc-short peptide was 96%.

[0111] Example 10:

[0112] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0113] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of N,N'-bis(2-hydroxyethyl)oxalamide (BHO), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially to a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain functionalized polyether (amide functionalization).

[0114] The theoretical number-average molecular weight M of the functionalized polyether was calculated by the feeding ratio of PO to BHO. n,th It is 4.6 kg / mol.

[0115] Using a series of PS standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 7.2 kg / mol and the dispersion to be 1.06.

[0116] 11H NMR characterization showed that the product had a well-defined structure and a amide functionalization degree of 99%.

[0117] Example 11:

[0118] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0119] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Cbz-L-valine (CbzVal), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially into a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain the functionalized polyether (Cbz-short peptide functionalization).

[0120] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feeding ratio of PO to CbzVal. n,th It is 4.6 kg / mol.

[0121] Using a series of PS standard samples as calibration curves, the SEC (SEC plot as shown) Figure 1 The molecular weight of the functionalized polyether was measured to be 7.5 kg / mol and the dispersion was 1.05. (As shown)

[0122] 1 H NMR characterization ( 1 H NMR image as follows Figure 2 As shown in the figure, the functionalization level of the Cbz-short peptide is 99%.

[0123] 1 H NMR and MALDI-TOF MS (MALDI-TOF MS curves are shown in Figure 1) Figure 3 The characterization shown (as indicated) fully demonstrates that the product structure is well-defined.

[0124] Example 12:

[0125] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0126] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Boc-valine-valine (BocVV), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially to a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain functionalized polyether (Boc-short peptide functionalization).

[0127] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feed ratio of PO to BocVV.n,th It is 4.6 kg / mol.

[0128] Using a series of PS standard samples as calibration curves, the SEC (SEC plot as shown) Figure 4 The molecular weight of the functionalized polyether was measured to be 6.4 kg / mol and the dispersion was 1.04. (As shown)

[0129] 1 H NMR characterization ( 1 H NMR image as follows Figure 5 As shown in the figure, the functionalization level of the Boc-short peptide is 100%.

[0130] 1 H NMR and MALDI-TOF MS characterization (MALDI-TOF MS curve as shown) Figure 6 As shown in the figure, the product structure is clearly defined.

[0131] The crude product of functionalized polyether (Boc-short peptide functionalization) was diluted with dichloromethane and thoroughly mixed with neutral alumina. The mixture was filtered, and the solvent was removed by rotary evaporation of the filtrate. The remaining liquid was then dried in a vacuum oven at 50°C for 12 hours to obtain the short peptide functionalized polyether. The purified product was then reacted with methanol and 1,5,7-triazabicyclo[4.4.0]decene-5-ene (TBD) at a ratio of 1:1200:30 at 60°C for 12 hours. Using a series of PS standard samples as calibration curves, the molecular weight of the product was determined by SEC to be 6.7 kg / mol, and the dispersity was 1.08. The polymer molecular weight remained almost unchanged before and after alcoholysis, indicating that in this embodiment, initiation was achieved only from the hydroxyl end, realizing selective initiation in a multiprotic system.

[0132] Example 13:

[0133] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0134] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Boc-glycine-glycine (BocGG), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially to a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain functionalized polyether (Boc-short peptide functionalization).

[0135] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feed ratio of PO to BocGG. n,th It is 4.6 kg / mol.

[0136] Using a series of PS standard samples as calibration curves, SEC determined that the molecular weight of the functionalized polyether before alcoholysis was 5.9 kg / mol and the dispersion was 1.06.

[0137] 1 1H NMR characterization showed that the product structure was well-defined, and the functionalization degree of the Boc-short peptide was 97%.

[0138] After alcoholysis (operation as in Example 12), the molecular weight of the product measured by SEC was 5.7 kg / mol, and the dispersity was 1.08.

[0139] The molecular weight of the polymer remained almost unchanged before and after alcoholysis, indicating that in this embodiment, initiation was only initiated from the hydroxyl end, achieving selective initiation in a multiprotic system.

[0140] Example 14:

[0141] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0142] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Boc-valine-glycine (BocVG), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially to a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain functionalized polyether (Boc-short peptide functionalization).

[0143] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feed ratio of PO to BocVG. n,th It is 4.6 kg / mol.

[0144] Using a series of PS standard samples as calibration curves, SEC determined that the molecular weight of the functionalized polyether before alcoholysis was 7.5 kg / mol and the dispersion was 1.05.

[0145] 1 1H NMR characterization showed that the product structure was well-defined, and the functionalization degree of the Boc-short peptide was 99%.

[0146] After alcoholysis (operation as in Example 12), the molecular weight of the product measured by SEC was 7.2 kg / mol, and the dispersity was 1.08.

[0147] The polymer molecular weight remained almost unchanged before and after alcoholysis, indicating that in this embodiment, initiation was only initiated from the hydroxyl end, achieving selective initiation in a multiprotic system.

[0148] Example 15:

[0149] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0150] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Cbz-glycine-proline (CbzGP), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially into a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain the functionalized polyether (Cbz-short peptide functionalization).

[0151] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feeding ratio of PO to CbzGP. n,th It is 4.6 kg / mol.

[0152] Using a series of PS standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 6.8 kg / mol and the dispersion to be 1.04.

[0153] 1 1H NMR characterization showed that the product structure was well-defined and the functionalization degree of the Cbz-short peptide was 98%.

[0154] Example 16:

[0155] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0156] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Cb2-tryptophan-tryptophan (Cb2TT), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially into a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain the functionalized polyether (Cbz-short peptide functionalization).

[0157] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feeding ratio of PO to CbzTT. n,th It is 4.6 kg / mol.

[0158] Using a series of PS standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 7.1 kg / mol and the dispersion to be 1.05.

[0159] 1 1H NMR characterization showed that the product structure was well-defined and the functionalization degree of the Cbz-short peptide was 96%.

[0160] Example 17:

[0161] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0162] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Boc-leucine-leucine (BocLL), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially to a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain functionalized polyether (Boc-short peptide functionalization).

[0163] The theoretical number-average molecular weight M of the functionalized polyether was calculated by the feeding ratio of PO to BocLL. n,th It is 4.6 kg / mol.

[0164] Using a series of PS standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 7.4 kg / mol and the dispersion to be 1.06.

[0165] 1 1H NMR characterization showed that the product structure was well-defined and the functionalization degree of the Boc-short peptide was 95%.

[0166] Example 18:

[0167] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0168] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Boc-leucine-glycine (BocLG), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially to a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain functionalized polyether (Boc-short peptide functionalization).

[0169] The theoretical number-average molecular weight M of the functionalized polyether was calculated by the feeding ratio of PO to BocLG. n,th It is 4.6 kg / mol.

[0170] Using a series of PS standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 6.6 kg / mol and the dispersion to be 1.04.

[0171] 1 1H NMR characterization showed that the product structure was well-defined, and the functionalization degree of the Boc-short peptide was 97%.

[0172] Example 19:

[0173] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0174] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Boc-alanine-glycine (BocAG), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially to a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain functionalized polyether (Boc-short peptide functionalization).

[0175] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feeding ratio of PO to BocAG. n,th It is 4.6 kg / mol.

[0176] Using a series of PS standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 6.3 kg / mol and the dispersion to be 1.07.

[0177] 1 1H NMR characterization showed that the product structure was well-defined, and the functionalization degree of the Boc-short peptide was 98%.

[0178] Example 20:

[0179] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0180] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Boc-alanine-proline (BocAP), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially to a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain functionalized polyether (Boc-short peptide functionalization).

[0181] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feed ratio of PO to BocAP. n,th It is 4.6 kg / mol.

[0182] Using a series of PS standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 6.9 kg / mol and the dispersion to be 1.04.

[0183] 1 The H NMR characterization of the product showed a clear structure, and the functionalization degree of the Boc-short peptide was 99%.

[0184] Example 21:

[0185] A method for synthesizing functionalized polyethers in a multiprotic system, comprising the following steps:

[0186] In a nitrogen atmosphere, 20 mmol of propylene oxide (PO), 0.25 mmol of Boc-valine-alanine (BocVA), and 0.0125 mmol of phosphazene base were added. t BuP2 and 0.0375 mmol of triethylboron were added sequentially to a glass reaction vessel, the glass reaction vessel was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 h to obtain functionalized polyether (Boc-short peptide functionalization).

[0187] The theoretical number-average molecular weight M of the functionalized polyether was calculated based on the feeding ratio of PO to BocVA. n,th It is 4.6 kg / mol.

[0188] Using a series of PS standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether to be 6.8 kg / mol and the dispersion to be 1.05.

[0189] 1 1H NMR characterization showed that the product structure was well-defined and the functionalization degree of the Boc-short peptide was 100%.

[0190] The above embodiments are preferred embodiments of the present invention, but the embodiments of the present invention are not limited to the above embodiments. Any changes, modifications, substitutions, combinations, or simplifications made without departing from the spirit and principle of the present invention shall be considered equivalent substitutions and shall be included within the protection scope of the present invention.

Claims

1. A method for synthesizing functionalized polyethers in a multiproton system, characterized in that, Includes the following steps: Polymerization reaction of epoxy monomers, amino alcohols or amino acid compounds, organic bases and alkyl borons yields urethane / amide / short peptide functionalized polyethers. The structural formula of the amino alcohol compound is as follows: or In the formula, R0 is tert-butyl or benzyl, and R1 is hydrogen, methyl, isopropyl, tert-butyl, sec-butyl, n-butyl, ... R2 is one of phenyl, hydroxymethyl, or hydroxyethyl, and R2 is methyl, vinyl, or... One of phenyl groups, where n is an integer from 1 to 9; The amino acid compound is One of the short peptides protected by the Boc / Cbz group, wherein R0 is tert-butyl or benzyl, and R3 is hydrogen, methyl, isopropyl, sec-butyl, 2-methylbutyl, ... , One of benzyl, phenethyl, p-hydroxybenzyl, hydroxymethyl, hydroxyethyl, 2-hydroxypropyl, carboxymethyl, and carboxyethyl, where n is an integer from 1 to 9.

2. The method for synthesizing functionalized polyethers in a multiproton system according to claim 1, characterized in that: The molar ratio of the epoxy monomer, amino alcohol / acid compound, organic base, and alkyl boron is 1–1000:1:0.01–3:0.01–5.

3. The method for synthesizing functionalized polyethers in a multiproton system according to claim 1 or 2, characterized in that: The epoxy monomer is ethylene oxide, C1-C6. 20 Straight-chain alkyl-substituted ethylene oxide, styrene oxide, cyclohexane oxide, 4-vinylcyclohexane oxide, limonene oxide, C1-C 16 At least one of the following: linear alkyl glycidyl ether, isopropyl glycidyl ether, tert-butyl glycidyl ether, 2-ethylhexyl glycidyl ether, phenyl glycidyl ether, benzyl glycidyl ether, allyl glycidyl ether, propargyl glycidyl ether, and glycidyl methacrylate.

4. The method for synthesizing functionalized polyethers in a multiprotic system according to claim 1 or 2, characterized in that: The organic base is at least one of the following: tertiary amine, amidine, guanidine, triaminophosphine, phosphazene base, lithium / sodium / potassium / cesium tert-butoxide, lithium / sodium / potassium / cesium / ammonium tert-valerate, thiourea, urea, and carbamate.

5. The method for synthesizing functionalized polyethers in a multiprotic system according to claim 1 or 2, characterized in that: The alkylborane is at least one of β-isopinepine-9-boronbicyclo[3.3.1]nonane, trisec-butylborane, triisopropylborane, trimethylborane, and tri(C2-C8 straight-chain alkyl)borane.

6. The method for synthesizing functionalized polyethers in a multiprotic system according to claim 1 or 2, characterized in that: The polymerization reaction is carried out at a temperature of 0℃ to 60℃ for a reaction time of 1h to 48h.

7. The method for synthesizing functionalized polyethers in a multiprotic system according to claim 1 or 2, characterized in that: The polymerization reaction is carried out in a solvent system, and the solvent is at least one selected from benzene, toluene, tetrahydrofuran, 2-methyltetrahydrofuran, n-hexane, cyclohexane, acetone, ethyl acetate, and tert-butanol.

8. The method for synthesizing functionalized polyethers in a multiprotic system according to claim 1 or 2, characterized in that: The polymerization reaction is carried out in a protective atmosphere.

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