Method for synthesizing functional polyether in multi-proton system

Abstract

The invention 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, organic alkali and alkyl boron for polymerization reaction to obtain carbamate / amide / oligopeptide functional polyether. According to the invention, the hydroxyl is preferentially activated in a multi-proton system by utilizing an acidic reversal phenomenon of an NH type proton group and the hydroxyl in a double-component organic catalytic system, so that a polymerization reaction is only carried out at a hydroxyl / carboxyl terminal; and finally, carbamate / amide / oligopeptide functional polyether with controllable molecular weight and a clear end group structure can be synthesized in a site selective manner through a one-step reaction, and the method is simple, convenient, efficient, controllable and suitable for large-scale industrial application.

Description

Technical Field

[0001] The invention relates to the technical field of polymer synthesis, and in particular to a method for synthesizing functionalized polyether in a multi-proton system. Background Art

[0002] Functional groups can not only enrich or improve the mechanical, thermal, optical, electrical, crystallization, rheological, mechanical, solution, interface, biocompatibility and other properties of polymer materials, but also enable polymers to obtain specific chemical reactivity to evolve their structure and properties, or couple with other small molecules, polymers, biomacromolecules, solids or micro / nanoparticle surfaces to construct complex drug systems or material systems. Therefore, quantitative and fixed-point introduction of functional groups into polymer structures is one of the focuses of polymer synthesis research.

[0003] It is well known that 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 end or center of a polymer chain. This method integrates polymer synthesis and functionalization, has significant step economy, and has modular characteristics. It is very easy to expand and can obtain functionalized polymers with rich structures and properties without changing the existing synthesis path, process and equipment. However, the harsh reaction conditions required for polymerization often lead to incompatibility between the functionalized initiator and the functional group located at the initiator or the initiating end of the polymer chain. The latter may interact or react with the monomer, catalyst, and chain growth active end, resulting in polymerization inactivation or loss of control, and ultimately the target polymer structure cannot be obtained.

[0004] At present, aliphatic polyethers represented by polyethylene oxide (also known as polyethylene glycol, PEO / PEG) and polypropylene oxide (PPO) have large production and extremely wide applications, and the end group is the key factor that determines their performance. Anionic ring-opening polymerization of epoxy monomers is a common method for synthesizing aliphatic polyethers, but functional groups with high chemical reactivity, especially electrophilic and protic functional groups, are often difficult to stably exist during anionic ring-opening polymerization. Therefore, it is necessary to use an indirect method to first introduce functional groups with low activity and compatible with ring-opening polymerization, and then introduce the target functional groups through coupling reactions. This process often introduces additional atoms or groups as connections, which ultimately affects the performance of the product. In recent years, with the continuous development of catalytic and initiation systems for anionic ring-opening polymerization, the chemical selectivity or functional group tolerance of this type of polymerization reaction has been greatly improved. Functionalized initiators can be used to directly introduce some reactive functional groups or precursor groups that are easy to convert (deprotect) into target functional groups, which greatly improves the synthesis efficiency and accuracy of functionalized polyethers. However, the functionalized initiators currently used are limited to (thio)carboxylic acids or monoprotic compounds containing hydroxyl (OH) and electrophilic functional groups (e.g., carbon-carbon double bonds, carboxylates), and it is still unknown whether initiators containing multiple protic functional groups can complete selective initiation and one-step conversion into structurally controllable functionalized polyethers.

[0005] Multiproton compounds (e.g. amino acid compounds, amino alcohol compounds) are widely present in biomass raw materials. If such compounds can be controllably introduced into polymer structures as functional groups, it will greatly enrich or enhance the physical, chemical and biological properties of polymer materials. However, in addition to the classic initiating groups (e.g., hydroxyl and carboxyl), these compounds also contain proton groups such as carbamate (amino protecting group) and amide. 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 the classic anionic ring-opening polymerization system based on strong alkaline catalysts or initiators, the NH-type proton groups will be preferentially activated (deprotonated), and the resulting carbamate or amide anions will 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), which is also a common problem in multi-proton ring-opening polymerization systems.

[0006] Studies have shown that the non-covalent interaction formed in situ between the amino group and the alkyl boron can be used to reduce the activity of the amino group, so that it can be stably present in the anionic ring-opening polymerization process of the epoxy monomer, so that the reaction occurs only at the hydroxyl end, and finally the one-step synthesis of the amino-functionalized polyether can be achieved (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 terminal amino-functionalized polyether), but this non-covalent interaction is relatively weak, the protection of the amino group is easily destroyed, and the product stability and post-processing flexibility are limited (for example: it is difficult to selectively modify the hydroxyl end of the polymer), and when the molecular weight of the target polymer is small, the non-covalent protection method requires the use of a large amount of toxic and flammable alkyl boron, which is costly and has a greater safety risk, and it is difficult to meet the requirements of practical applications.

[0007] Therefore, it is of great significance to develop a controllable synthesis method for functionalized polyethers suitable for multi-proton systems. Summary of the invention

[0008] The object of the present invention is to provide a method for synthesizing functionalized polyether in a multi-proton system.

[0009] The technical solution adopted by the present invention is:

[0010] A method for synthesizing functionalized polyether in a multi-proton system comprises the following steps: epoxy monomer, amino alcohol / acid compound, organic base and alkyl boron are mixed and polymerized to obtain carbamate / amide / short peptide functionalized polyether.

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

[0012] More preferably, the molar ratio of the epoxy monomer, the amino alcohol / acid compound, the organic base, and the 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 0.2-0.5:1.

[0015] Preferably, the epoxy monomer is ethylene oxide, C1-C 20Straight chain alkyl substituted ethylene oxide, styrene oxide, cyclohexene oxide, 4-vinyl cyclohexene oxide, limonene oxide, C1~C 16 At least one of straight-chain 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, the structural formula of which is as follows:

[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 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, R2 is methyl, vinyl, A phenyl group, wherein n is an integer from 1 to 9.

[0019] Further preferably, the amino alcohol compound is at least one of Boc-alkylolamine, Boc-D-aminopropanol, Boc-D-valinol, Boc-L-valinol, Boc-L-tert-leucinol, Boc-L-isoleucinol, Boc-L-norleucinol, Boc-L-methioninol, Boc-L-phenylalaninol, Boc-serinol, Boc-D-threoninol, Boc-4-hydroxyaniline, Boc-4-aminobenzyl alcohol, Boc-2-(4-aminophenyl)ethanol, N-acetylethanolamine, N-(2-hydroxyethyl)acrylamide, N,N'-bis(2-hydroxyethyl)oxamide, and N-(2-hydroxyethyl)benzamide.

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

[0021] Preferably, the amino acid compound is One of the short peptides protected by Boc / Cbz groups, 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, wherein n is an integer of 1 to 9.

[0022] Further preferably, the amino acid compound is Boc-(4-aminophenyl)formic 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, 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 -L-threonine, Boc-L-aspartic acid, Cbz-L-aspartic acid, Boc-L-glutamic acid, Cbz-L-glutamate, 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, Boc-leucine-valine-valine, Boc-valine-glycine-phenylalanine.

[0023] The structural formulas of some amino alcohol / acid compounds are as follows:

[0024]

[0025] Preferably, the organic base is at least one of tertiary amine, amidine, guanidine, triaminophosphine, phosphazene base, lithium / sodium / potassium / cesium tert-butoxide, lithium / sodium / potassium / cesium / ammonium pivalate, thiourea, urea, and carbamate.

[0026] Further 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 structural formula as follows:

[0027]

[0028] Preferably, the alkyl boron is B-isopinocampheyl-9-borabicyclo[3.3.1]nonane (S-Alphine-Borane), tri-sec-butylborane (T s BuB), triisopropylborane (T i At least one of PrB), trimethylborane (TMB), tri(C2-C8 linear alkyl)borane (TAB), the structural formula is as follows:

[0029]

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

[0031] Further preferably, the polymerization reaction is carried out at room temperature (25°C±5°C) and the reaction time is 2h to 10h.

[0032] Preferably, the polymerization reaction is carried out in a solvent system, and the solvent is at least one of 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 the present invention are as follows: the present invention utilizes the acid reversal phenomenon of NH type proton groups and hydroxyl groups in a two-component organic catalytic system to preferentially activate the hydroxyl groups in a multi-proton system, thereby allowing the polymerization reaction to proceed only at the hydroxyl / carboxyl end, and finally, through a one-step reaction, site-selectively synthesizing carbamate / amide / short peptide functionalized polyethers with controllable molecular weight and clear end group structure; the method is simple, efficient, controllable, and 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 pairs of catalysts (organic bases + alkyl boron) in a multi-proton system for the first time to achieve acid reversal of NH-type proton groups (carbamates, amides, etc.) and OH groups, so that the epoxy monomer reacts only with OH or COOH, and site-selective initiation is achieved (in conventional anionic ring-opening polymerization under strong alkaline conditions, NH-type proton groups are preferentially activated, and chain transfer to OH can occur after the initiation is completed, so site-selective initiation cannot be achieved). The method is simple, efficient, and controllable to synthesize functionalized polyethers in one step, and has significant step economy compared to the post-polymerization modification method;

[0039] 2) Compared with the non-covalent amino protection strategy, the method for synthesizing functionalized polyethers of the present invention uses a lower amount of catalyst, and the protecting group is more stable, and the polymer purification process does not cause deprotection, so the amino end can be selectively modified by the commonly used Boc group (tert-butyloxycarbonyl) and / or Cbz group (benzyloxycarbonyl), and then a simple deprotection treatment can be performed to release the amino group;

[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 to 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 chromatography separation and ion exchange resin separation, and 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 source properties (renewable), are cheap and easy to obtain, have a high degree of commercialization, and have extremely rich structures. The use of the initiator in synthesizing functionalized polymers meets the requirements of green and sustainable development;

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

[0043] 6) The functionalized polyether obtained by the method for synthesizing the functionalized polyether of the present invention has no heavy metal residues and is more suitable for application in high-tech industries such as biomedicine and microelectronics. BRIEF DESCRIPTION OF THE DRAWINGS

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

[0045] Figure 2 is the functionalized polyether in Example 11 1 H NMR spectra.

[0046] Figure 3 This is the MALDI-TOF MS curve of the functionalized polyether in Example 11.

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

[0048] Figure 5 is the functionalized polyether in Example 12 1 H NMR spectra.

[0049] Figure 6 This is the MALDI-TOF MS curve of the functionalized polyether in Example 12. DETAILED DESCRIPTION

[0050] The present invention will be further explained and illustrated below in conjunction with specific embodiments.

[0051] The conversion rate of epoxy monomer and the structural characteristics of polymer were measured by Bruker AV400 liquid nuclear magnetic resonance spectrometer ( 1 HNMR) was measured, and the solvent was deuterated chloroform or dimethyl sulfoxide (DMSO).

[0052] The molecular weight and dispersity of the polyether were measured using an Agilent 1260 Infinity size exclusion chromatograph from the United States, with tetrahydrofuran (THF) as the mobile phase, a column temperature of 35°C, and a flow rate of 1 mL / min; a series of polystyrene (PS) or polyethylene oxide (PEG) standard samples were used as calibration curves.

[0053] Embodiment 1:

[0054] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

[0056] THF, BocEA and EO were used after being purified and dehydrated.

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

[0058] Using a series of PEG standard samples as the calibration curve, SEC (size exclusion chromatography) measured the molecular weight of the functionalized polyether to be 1.7 kg / mol and the dispersity to be 1.07.

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

[0060] 1 The characterizations of H NMR and matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) fully demonstrated that the product had a clear structure.

[0061] Acid deprotection of functionalized polyether (carbamate functionalized): 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 ether for precipitation. The precipitate was collected and vacuum dried to obtain amino-functionalized polyether.

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

[0063] Embodiment 2:

[0064] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

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

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

[0068] 1H NMR characterization showed that the product had a clear structure and the degree of carbamate functionalization was 98%.

[0069] Embodiment 3:

[0070] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

[0071] In a nitrogen atmosphere, 1.3 mmol of Boc-aminoethanol (BocEA), 0.0325 mmol of phosphazene base t BuP2, 0.13 mmol of triethylboron and 3 mL of toluene were added to a dry glass reactor in sequence and stirred evenly. The glass reactor was then connected to a vacuum line, part of the gas in the glass reactor was removed, and the temperature was cooled with an ice water bath. Then, 58.5 mmol of ethylene oxide (EO, [EO]0 = 10 mol / L) was added at -20°C, and the glass reactor was sealed and reacted at room temperature for 3 h. The glass reactor was then opened, chloroform was added, and then poured into ether for precipitation. The precipitate was collected and dried in vacuo to obtain a functionalized polyether (carbamate functionalized).

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

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

[0074] 1 H NMR characterization showed that the product had a clear structure and the degree of carbamate functionalization was 99%.

[0075] Embodiment 4:

[0076] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

[0077] In a nitrogen atmosphere, 1.3 mmol of Boc-aminoethanol (BocEA), 0.0325 mmol of phosphazene base t BuP2, 0.13 mmol of triisopropylborane (T iPrB) and 3mL of tetrahydrofuran (THF) were added to a dry glass reactor in sequence and stirred evenly. The glass reactor was then connected to a vacuum line, part of the gas in the glass reactor was removed, and an ice water bath was used to cool it down. Then, 58.5mmol of ethylene oxide (EO, [EO]0=10mol / L) was added at -20°C, and the glass reactor was sealed and reacted at room temperature for 4h. The glass reactor was then opened, chloroform was added, and then poured into ether for precipitation. The precipitate was collected and dried in vacuum to obtain a functionalized polyether (urethane functionalized).

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

[0079] Using a series of PEG standard samples as the calibration curve, SEC measured the molecular weight of the functionalized polyether to be 1.8 kg / mol and the dispersity to be 1.06.

[0080] 1 H NMR characterization showed that the product had a clear structure and the degree of carbamate functionalization was 96%.

[0081] Embodiment 5:

[0082] A method for synthesizing functionalized polyether in a multi-proton 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 added to a dry glass reactor in sequence and stirred evenly. The glass reactor was then connected to a vacuum line, part of the gas in the glass reactor was removed, and the temperature was cooled with an ice water bath. Then, 58.5 mmol of ethylene oxide (EO, [EO]0 = 10 mol / L) was added at -20°C, and the glass reactor was sealed and reacted at room temperature for 6 h. The glass reactor was then opened, chloroform was added, and then poured into ether for precipitation. The precipitate was collected and vacuum dried to obtain a functionalized polyether (carbamate functionalized).

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

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

[0086] 1H NMR characterization showed that the product had a clear structure and the degree of carbamate functionalization was 97%.

[0087] Embodiment 6:

[0088] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

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

[0091] Using a series of PEG standard samples as the calibration curve, SEC measured the molecular weight of the functionalized polyether to be 5.2 kg / mol and the dispersity to be 1.05.

[0092] 1 H NMR characterization showed that the product had a clear structure and the degree of carbamate functionalization was 100%.

[0093] Embodiment 7:

[0094] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

[0095] In a nitrogen atmosphere, 0.25 mmol of Boc-serinol (BocSr), 0.00625 mmol of phosphazene base tBuP2, 0.025 mmol of triethylboron and 3 mL of tetrahydrofuran (THF) were added to a dry glass reactor in sequence and stirred evenly. The glass reactor was then connected to a vacuum line, part of the gas in the glass reactor was removed, and the temperature was cooled with an ice water bath. 27.5 mmol of ethylene oxide (EO, [EO]0 = 10 mol / L) was added at -20°C, and the sealed glass reactor was reacted at room temperature for 3 h. The glass reactor was then opened, chloroform was added, and then poured into ether for precipitation. The precipitate was collected and dried in vacuo to obtain a functionalized polyether (carbamate functionalized).

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

[0097] Using a series of PEG standard samples as the calibration curve, SEC measured the molecular weight of the functionalized polyether to be 4.6 kg / mol and the dispersity to be 1.04.

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

[0099] Embodiment 8:

[0100] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

[0101] In a nitrogen atmosphere, 0.25 mmol of Boc-valine-valine (BocVV), 0.00625 mmol of phosphazene base t BuP2, 0.025 mmol of triethylboron and 3 mL of tetrahydrofuran (THF) were added to a dry glass reactor in sequence and stirred evenly. The glass reactor was then connected to a vacuum line, part of the gas in the glass reactor was removed, and an ice water bath was used for cooling. Then, 27.5 mmol of ethylene oxide (EO, [EO]0 = 10 mol / L) was added at -20°C, and the sealed glass reactor was reacted at room temperature for 3 h. The glass reactor was then opened, chloroform was added, and then poured into ether for precipitation. The precipitate was collected and dried in vacuo to obtain a functionalized polyether (Boc-short peptide functionalization).

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

[0103] Using a series of PEG standard samples as the calibration curve, SEC measured the molecular weight of the functionalized polyether to be 5.0 kg / mol and the dispersity to be 1.05.

[0104] 1 H NMR characterization showed that the product had a clear structure and the functionalization degree of Boc-peptide was 99%.

[0105] Embodiment 9:

[0106] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

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

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

[0110] 1 H NMR characterization showed that the product had a clear structure and the functionalization degree of Boc-peptide was 96%.

[0111] Embodiment 10:

[0112] A method for synthesizing functionalized polyether in a multi-proton 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), 0.0125 mmol of phosphazene base t BuP2 and 0.0375 mmol of triethylboron were added to a glass reaction container in sequence, the glass reaction container was sealed, a magnetic stirrer was turned on, and the reaction was carried out at room temperature for 5 hours to obtain a functionalized polyether (amide functionalized).

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

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

[0116] 1H NMR characterization showed that the product had a clear structure and the degree of amide functionalization was 99%.

[0117] Embodiment 11:

[0118] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

[0120] The theoretical number average molecular weight M of the functionalized polyether was calculated by the feed ratio of PO and CbzVal. n,th It is 4.6kg / mol.

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

[0122] 1 H NMR characterization ( 1 H NMR images Figure 2 The functionalization degree of Cbz-peptide was 99%.

[0123] 1 H NMR and MALDI-TOF MS (MALDI-TOF MS curves are shown in Figure 3 The characterization of the product is clear.

[0124] Embodiment 12:

[0125] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

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

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

[0129] 1 H NMR characterization ( 1 H NMR images Figure 5 ) shows that the functionalization degree of Boc-peptide is 100%.

[0130] 1 H NMR and MALDI-TOF MS characterization (MALDI-TOF MS curves are shown in Figure 6 The product structure is clearly shown.

[0131] The crude product of functionalized polyether (Boc-short peptide functionalization) was diluted with dichloromethane and fully mixed with neutral alumina, filtered, and the filtrate was evaporated to remove the solvent, and the remaining liquid was placed in a vacuum oven at 50°C and dried at a constant temperature for 12 hours to obtain short peptide functionalized polyether, and then the purified product was 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. The molecular weight of the product measured by SEC with a series of PS standard samples as the calibration curve was 6.7kg / mol and the dispersity was 1.08. The molecular weight of the polymer was almost unchanged before and after alcoholysis, indicating that the selective initiation in the multi-proton system was achieved only from the hydroxyl end in this embodiment.

[0132] Embodiment 13:

[0133] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

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

[0136] Using a series of PS standard samples as calibration curves, SEC measured the molecular weight of the functionalized polyether before alcoholysis to be 5.9 kg / mol and the dispersity to be 1.06.

[0137] 1 H NMR characterization showed that the product had a clear structure and the functionalization degree of Boc-peptide was 97%.

[0138] After alcoholysis (same 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 hardly changes before and after alcoholysis, indicating that in this embodiment, initiation is only carried out from the hydroxyl end, thus achieving selective initiation in a multi-proton system.

[0140] Embodiment 14:

[0141] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

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

[0144] Using a series of PS standard samples as the calibration curve, SEC measured the molecular weight of the functionalized polyether before alcoholysis to be 7.5 kg / mol and the dispersity to be 1.05.

[0145] 1 H NMR characterization showed that the product had a clear structure and the functionalization degree of Boc-peptide was 99%.

[0146] After alcoholysis (same 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 molecular weight of the polymer hardly changes before and after alcoholysis, indicating that in this embodiment, initiation is only carried out from the hydroxyl end, thus achieving selective initiation in a multi-proton system.

[0148] Embodiment 15:

[0149] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

[0151] The theoretical number average molecular weight M of the functionalized polyether was calculated by the feed ratio of PO and CbzGP. n,th It is 4.6kg / mol.

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

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

[0154] Embodiment 16:

[0155] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

[0157] The theoretical number average molecular weight M of the functionalized polyether was calculated by the feed ratio of PO and CbzTT. n,th It is 4.6kg / mol.

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

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

[0160] Embodiment 17:

[0161] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

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

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

[0165] 1 H NMR characterization showed that the product had a clear structure and the functionalization degree of Boc-peptide was 95%.

[0166] Embodiment 18:

[0167] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

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

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

[0171] 1 H NMR characterization showed that the product had a clear structure and the functionalization degree of Boc-peptide was 97%.

[0172] Embodiment 19:

[0173] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

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

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

[0177] 1 H NMR characterization showed that the product had a clear structure and the functionalization degree of Boc-peptide was 98%.

[0178] Embodiment 20:

[0179] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

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

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

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

[0184] Embodiment 21:

[0185] A method for synthesizing functionalized polyether in a multi-proton system, comprising the following steps:

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

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

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

[0189] 1 H NMR characterization showed that the product had a clear structure and the functionalization degree of Boc-peptide was 100%.

[0190] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for synthesizing functionalized polyethers in a multi-proton system, characterized in that: The following steps are involved: The epoxy monomer, amino alcohol / acid compound, organic base and alkyl boron are mixed and polymerized to obtain carbamate / amide / short peptide functionalized polyether.

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

3. The method for synthesizing functionalized polyether in a multi-proton system according to claim 1 or 2, characterized in that: The epoxy monomer is ethylene oxide, C1~C 20 Straight chain alkyl substituted ethylene oxide, styrene oxide, cyclohexene oxide, 4-vinyl cyclohexene oxide, limonene oxide, C1~C 16 At least one of straight-chain 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 polyether in a multi-proton system according to claim 1 or 2, characterized in that: The structural formula of the amino alcohol compound is 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, R2 is methyl, vinyl, A phenyl group, wherein n is an integer from 1 to 9.

5. The method for synthesizing functionalized polyether in a multi-proton system according to claim 1 or 2, characterized in that: The amino acid compound is One of the short peptides protected by Boc / Cbz groups, 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, wherein n is an integer of 1 to 9.

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

7. The method for synthesizing functionalized polyether in a multi-proton system according to claim 1 or 2, characterized in that: The alkyl boron is at least one of B-isopinocampheyl-9-borabicyclo[3.3.1]nonane, tri-sec-butylborane, triisopropylborane, trimethylborane and tri(C2-C8 straight-chain alkyl)borane.

8. The method for synthesizing functionalized polyether in a multi-proton system according to claim 1 or 2, characterized in that: The polymerization reaction is carried out at a temperature of 0°C to 60°C and a reaction time of 1h to 48h.

9. The method for synthesizing functionalized polyether in a multi-proton 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 of benzene, toluene, tetrahydrofuran, 2-methyltetrahydrofuran, n-hexane, cyclohexane, acetone, ethyl acetate, and tert-butanol.

10. The method for synthesizing functionalized polyether in a multi-proton system according to claim 1 or 2, characterized in that: The polymerization reaction is carried out in a protective atmosphere.

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