Synthesis method of polyvaline
By employing N-thiocarboxylic anhydride of valine and ultrasound-assisted polymerization technology, the problems of poor solubility and wide molecular weight distribution in polyvaline synthesis have been solved, achieving efficient and controllable polyvaline synthesis and enhancing its application potential in the biomedical field.
Patent Information
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- JIAXING UNIV
- Filing Date
- 2025-12-17
- Publication Date
- 2026-04-21
AI Technical Summary
Existing technologies for polyvaline synthesis face challenges such as high operational difficulty, high cost, poor product solubility, wide molecular weight distribution, and difficulty in precise control, which limit its application in the biomedical field.
By using valine N-thiocarboxylic anhydride as a monomer and combining it with ultrasound-assisted polymerization technology, and by selecting specific initiators and solvents to control reaction conditions, a highly efficient and controllable synthesis of polyvaline can be achieved.
The efficient and controllable synthesis of polyvaline was achieved, and the product has a narrow molecular weight distribution, good solubility and excellent processing performance, which expands its application potential in the biomedical field.
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Figure CN121895572A_ABST
Abstract
Description
Technical Field
[0001] This invention relates to the field of organic compound synthesis technology, and in particular to a method for synthesizing polyvaline. Background Technology
[0002] Poly(amino acid) (PAA) is an important class of biopolymers. Its basic structural unit is the α-amino acid residue, which shares a high structural similarity with natural proteins and peptides, thus exhibiting excellent biocompatibility. The diverse range of R groups in the side chains of PAA endows it with varied physicochemical properties. For example, polylysine and polyglutamic acid exhibit pH responsiveness, polyalanine and polyphenylalanine are oil-soluble, and polyserine and polysarcosine are water-soluble. These properties make PAA irreplaceable in biomedical fields such as drug delivery, biosensors, and tissue engineering.
[0003] Valine, a simple natural amino acid, can form regular antiparallel β-sheet structures within polyamino acid chains, thus constituting structurally stable crystalline regions. Therefore, polymers containing valine residues are potential high-performance biomaterials with broad application prospects in drug carriers, high-strength biomedical materials, and other fields. However, the synthesis of polyvaline in current technologies faces numerous technical bottlenecks, severely limiting its industrial application and functional expansion. Firstly, traditional polyvaline synthesis often uses α-amino acid N-carboxylic anhydride (NCA) as a monomer, prepared via ring-opening polymerization (ROP). However, NCA monomers are extremely sensitive to water and heat, requiring stringent anhydrous conditions for polymerization, resulting in high operational difficulty and cost. Furthermore, the polymerization reaction exhibits poor tolerance to nucleophilic groups such as hydroxyl groups, making mass production difficult. Secondly, the polymerization rate of NCA monomers is much faster than that of other carbon- and nitrogen-substituted α-amino acid NCA monomers. This results in uneven distribution of valine residues when copolymerized with other amino acid NCAs, leading to extremely poor solubility of the polymer product. Precipitation often forms in the early stages of polymerization, hindering the continued polymerization reaction. Furthermore, the product is insoluble and infusible, exhibiting poor processability and failing to meet the requirements for subsequent material molding. In addition, existing chemical synthesis methods struggle to precisely control the molecular weight of polyvaline, resulting in a wide molecular weight distribution of the product. Moreover, the inability to chemically introduce alternating chiral structures makes it difficult to mimic the complex structure and function of natural peptides, further limiting its application in high-end biomedical materials.
[0004] To address the aforementioned technical problems, this invention proposes a method for synthesizing polyvaline. Using valine N-thiocarboxylic anhydride (NTA) as a monomer and combining it with ultrasound-assisted polymerization technology, this method achieves efficient and controllable synthesis of polyvaline. It also solves the core problems of traditional methods, such as poor product solubility, poor processing performance, and wide molecular weight distribution, providing a feasible solution for the industrial application of polyvaline. Summary of the Invention
[0005] This invention addresses the shortcomings of existing technologies by providing a method for synthesizing polyvaline that is efficient, controllable, and stable. The resulting polyvaline exhibits characteristics such as narrow molecular weight distribution, good solubility, and excellent processing performance, and has broad application prospects in biomedical fields such as drug delivery, tissue engineering, and biosensors.
[0006] Therefore, the purpose of this invention is to provide a method for synthesizing polyvaline.
[0007] To achieve the objective of this invention, the technical solution of this invention provides a method for synthesizing polyvaline, comprising the following steps: S100, adding valine N-thiocarboxylic anhydride, an initiator, and an organic solvent to a reactor, mixing and stirring to obtain a first reactant; S200, subjecting the first reactant to an ultrasonic reaction to obtain a second reactant; S300, precipitating the second reactant in an extractant, filtering, and vacuum drying to obtain polyvaline.
[0008] Compared with existing technologies, this technical solution achieves the following advantages: Valine N-thiocarboxylic anhydride, as a polymerization monomer, exhibits higher stability to water and heat, and the polymerization reaction is more resistant to nucleophilic groups such as hydroxyl groups, providing a reliable foundation for the efficient synthesis of polyvaline; ultrasonication of the first reactant significantly increases the polymerization rate, greatly shortening the reaction cycle compared to traditional synthesis methods, enabling mass production of polyvaline within 1-7 days; precipitation of the second reactant in an extractant achieves efficient separation of polyvaline from unreacted monomers, initiator residues, and other impurities; subsequent filtration and vacuum drying further remove residual solvents and trace impurities from the product, ultimately yielding polyvaline with a narrow molecular weight distribution, high yield, and high purity. This synthetic method, through the synergistic effect of each step, successfully achieves the artificial synthesis of polyvaline. The product exhibits good solubility and excellent processing properties, overcoming the application defects of traditional homopolymer valine, such as poor solubility and unsatisfactory processing performance. Furthermore, by introducing an alternating chiral structure, it simulates the complex structure and function of natural peptides, expanding its application prospects in fields such as biomedical materials.
[0009] In one embodiment of the present invention, the hair-spraying agent is selected from at least one of amines containing C2-C9 aliphatic hydrocarbon functional groups.
[0010] Compared with existing technologies, the technical advantages achieved by this solution are as follows: The initiator is selected from at least one amine containing C2-C9 aliphatic hydrocarbon functional groups. Its aliphatic hydrocarbon structure has moderate steric hindrance and electronic effects, providing stable initiation activity for the ring-opening polymerization of valine N-thiocarboxylic anhydride monomers. This avoids uncontrolled polymerization due to excessive initiation activity, and also prevents reaction stagnation due to insufficient activity, ensuring a stable and controllable polymerization process. The chemical structure of this type of initiator is stable, without redundant unsaturated bonds or easily reactive heteroatoms, and it will not undergo side reactions with valine N-thiocarboxylic anhydride monomers, reducing the formation of by-products during polymerization and improving the purity of the polyvaline product. The stable end-group structure also reserves reaction sites for subsequent functionalization modifications of polyvaline, further expanding its application potential in fields such as biomedical materials.
[0011] In one embodiment of the present invention, in S100, the molar ratio of valine N-thiocarboxylic anhydride to initiator is (20-300):1; in S100, the organic solvent is selected from at least one of n-hexane, n-heptane, methanol, ethanol, and petroleum ether.
[0012] Compared with existing technologies, the technical effects achieved by this solution are as follows: In S100, the molar ratio of valine N-thiocarboxylic anhydride to initiator is limited to (20-25):1. This ratio range can precisely match the initiation activity of amine initiators with the ring-opening polymerization requirements of valine N-thiocarboxylic anhydride, avoiding the problems of excessive initiator due to too low a ratio resulting in a small molecular weight of the product, or too high a ratio resulting in monomer residue and incomplete polymerization. The number average molecular weight of polyvaline can be precisely controlled within the range of 2kDa-30kDa, while ensuring that the product dispersion is less than 1.2, achieving precise control of molecular weight and narrow distribution characteristics, and ensuring uniform polymer chain length. The organic solvent selected is at least one of n-hexane, n-heptane, methanol, ethanol, and petroleum ether. These solvents have good solubility and chemical stability, and can fully dissolve valine N-thiocarboxylic anhydride monomer and initiator, avoiding the disordered distribution of polymerization products or premature precipitation caused by uneven local concentrations. This provides a uniform and stable reaction environment for the polymerization reaction. At the same time, these solvents do not undergo side reactions with monomers and initiators, and are easily separated from subsequent extractants, which can reduce the introduction of impurities and ensure product purity. Combined with stirring, it can further improve the mixing uniformity of each reaction component, laying the foundation for the efficient conduct of subsequent ultrasound-assisted polymerization.
[0013] In one technical solution of the present invention, in S200, the temperature of the ultrasonic reaction is 15℃-50℃; in S200, the ultrasonic environment is 20W-100W.
[0014] Compared with existing technologies, the technical advantages of this solution are as follows: In S200, the ultrasonic reaction temperature is limited to 15℃-50℃. This temperature range is highly compatible with the stability range of valine N-thiocarboxylic anhydride monomer, avoiding the problems of slow monomer diffusion and decreased reaction rate caused by low temperatures, while preventing monomer decomposition or uncontrolled polymerization reaction caused by high temperatures. This ensures a stable and controllable polymerization process. Furthermore, it is in line with room temperature, representing mild reaction conditions, eliminating the need for additional complex temperature control equipment, thus reducing operational difficulty and energy consumption. The ultrasonic environment is set to a power range of 20W-100W, which effectively accelerates monomer diffusion and the formation of reactive centers, significantly increasing the polymerization rate. This shortens the long cycle of traditional synthesis methods to 1-7 days, enabling mass production of polyvaline. It also avoids problems such as localized overheating and excessively rapid solvent evaporation caused by excessively high power, reducing the occurrence of side reactions. Combined with a suitable reaction temperature, this ensures a narrow molecular weight distribution and uniform structure of the polyvaline product.
[0015] In one embodiment of the present invention, the extractant is selected from at least one of dichloromethane, tetrahydrofuran, diethyl ether, acetonitrile, ethyl acetate, methyl tert-butyl ether, and n-butanol.
[0016] Compared with existing technologies, the technical advantages achieved by this solution are as follows: The extractant is selected from at least one of dichloromethane, tetrahydrofuran, diethyl ether, acetonitrile, ethyl acetate, methyl tert-butyl ether, and n-butanol. These extractants have a significant solubility difference with polyvaline, resulting in low solubility and easy formation of stable precipitates. However, unreacted valine N-thiocarboxylic anhydride monomers and amine initiator residues from the polymerization reaction can be fully dissolved. This allows for rapid initial separation of the product from impurities through a simple precipitation process, significantly simplifying the post-processing steps. These extractants are chemically stable and do not undergo side reactions with polyvaline, preventing the introduction of impurities and ensuring the structural integrity and purity of the product. Furthermore, they exhibit good compatibility with organic solvents such as n-hexane used in the polymerization process, ensuring a stable precipitation process and preventing product agglomeration or purity degradation. In addition, these extractants have moderate volatility, allowing for efficient removal of residues through subsequent filtration and vacuum drying steps. This prevents solvent residues from affecting the solubility and processing properties of polyvaline, ensuring the final product maintains good solubility and processing compatibility.
[0017] In one technical solution of the present invention, valine N-thiocarboxylic anhydride is prepared by the following steps: S111, valine, sodium hydroxide, 2-((ethoxythiocarbonyl)thio)acetic acid and water are placed in a reactor for reaction to obtain a pre-precursor; S112, the pre-precursor is subjected to acidification, extraction, washing, drying, filtration and vacuum concentration in sequence to obtain a precursor; S113, the precursor is dissolved in an organic solvent, a cyclization catalyst is added, and a cyclization reaction is carried out to obtain a cyclization solution; S114, the cyclization solution is subjected to washing, drying, filtration, vacuum concentration and recrystallization in sequence to obtain valine N-thiocarboxylic anhydride.
[0018] Preferably, the cyclization catalyst is added slowly dropwise to a solution of the precursor dissolved in an organic solvent.
[0019] Preferably, during the dropwise addition of the cyclization catalyst, the reactor containing the precursor solution is placed in an ice-water bath.
[0020] Preferably, after the cyclization catalyst is added dropwise, the temperature is raised to room temperature for 10-20 minutes to start the cyclization reaction.
[0021] Compared with existing technologies, the technical advantages achieved by this solution are as follows: The four-step ordered preparation process of valine N-thiocarboxylic anhydride ensures the high purity and structural integrity of the monomer. S111 uses valine, sodium hydroxide, 2-((ethoxythiocarbonyl)thio)acetic acid, and water as reactants. The aqueous reaction environment is mild and the raw materials are readily available, eliminating the need for stringent anhydrous and oxygen-free conditions. The presence of sodium hydroxide promotes the dissociation of valine to form an active center, ensuring efficient reaction with thiocarboxylic acid to generate the pre-precursor, avoiding raw material waste and byproduct formation. S112 involves a continuous process of acidification, extraction, washing, drying, filtration, and vacuum concentration. Acidification completely protonates the pre-precursor to convert it into the target precursor; extraction separates the precursor from aqueous impurities; multiple washings remove residual salts and unreacted raw materials; and drying, filtration, and vacuum concentration further improve the purity of the precursor, laying the foundation for subsequent cyclization reactions. S113 involves dissolving the precursor in an organic solvent and adding a cyclization catalyst. The organic solvent provides a suitable reaction environment for the cyclization reaction, promoting precursor dissolution and catalyst dispersion. The cyclization catalyst efficiently activates the reaction sites of the precursor, driving intramolecular cyclization to form a stable N-thiocarboxylic anhydride five-membered ring structure, ensuring a complete cyclization reaction and a uniform product structure. S114 further removes inorganic impurities and catalyst residues generated during the cyclization reaction through repeated washing, drying, filtration, vacuum concentration, and recrystallization. The recrystallization step significantly improves the crystallinity and purity of the monomer, ultimately obtaining a high-purity valine N-thiocarboxylic anhydride monomer. This monomer exhibits higher water and thermal stability, effectively avoiding problems such as reaction interruption and wide product distribution caused by insufficient monomer purity or poor stability during polymerization. This provides a reliable monomer guarantee for the controllable synthesis of polyvaline. Furthermore, the entire preparation process is simple, controllable, and suitable for large-scale production, reducing the raw material costs and technical barriers to polyvaline synthesis.
[0022] In one technical solution of the present invention, in S111, valine, sodium hydroxide and 2-((ethoxythiocarbonyl)thio)acetic acid are added in a molar ratio of (0.8-1.2):(1.8-2.5):(0.8-1.2); in S111, the reaction temperature is 25°C and the reaction time is 48h-96h.
[0023] Compared with existing technologies, the technical advantages achieved by this solution are as follows: By controlling the molar ratio of raw materials, the reactivity can be adjusted, thereby controlling the rate and conversion of pre-precursor formation; the mild room temperature condition of 25℃ ensures the reactivity of each raw material while avoiding the decomposition or side reactions of 2-((ethoxythiocarbonyl)thio)acetic acid caused by high temperatures, and eliminates the need for complex temperature control equipment, reducing operational difficulty and energy consumption. Controlling the reaction time to 48-96 hours ensures a complete reaction, maximizing the conversion of raw materials into pre-precursors, avoiding raw material residues due to excessively short reaction times, and preventing product degradation caused by excessively long reaction times, thus ensuring the structural integrity and purity of the pre-precursor.
[0024] In one embodiment of the present invention, in step S112, the pH is acidified to 1-2; in step S112, the extractant is selected from at least one of dichloromethane, tetrahydrofuran, diethyl ether, acetonitrile, ethyl acetate, methyl tert-butyl ether, and n-butanol; in step S112, the washing liquid is selected from at least one of citric acid aqueous solution and saturated sodium chloride solution.
[0025] Compared with existing technologies, the technical effects achieved by this solution are as follows: Acidification in S112 to a pH of 1-2 ensures complete protonation of the pre-precursor into the target precursor, avoiding incomplete conversion due to insufficient acidification. Simultaneously, it inhibits precursor hydrolysis, ensuring structural stability. The extractant is selected from solvents such as dichloromethane, tetrahydrofuran, and diethyl ether. These extractants have good selective dissolving capabilities, efficiently separating inorganic salts and other impurities in the aqueous phase from the precursor in the oil phase, achieving preliminary purification of the precursor. The washing solution uses at least one of citric acid aqueous solution and saturated sodium chloride solution. Citric acid aqueous solution neutralizes residual alkaline substances, preventing the catalyst activity from being affected in subsequent cyclization reactions. Saturated sodium chloride solution removes trace amounts of water from the extractant through salting-out, reducing water interference in subsequent reactions. The synergistic effect of these two solutions deeply removes impurities from the precursor. Combined with drying, filtration, and vacuum concentration steps, the purity of the precursor is further improved.
[0026] In one embodiment of the present invention, in step S113, the organic solvent is selected from at least one of dichloromethane, tetrahydrofuran, diethyl ether, acetonitrile, ethyl acetate, methyl tert-butyl ether, and n-butanol; in step S113, the cyclization catalyst is selected from at least one of phosphorus tribromide, phosphorus oxybromide, phosphorus trichloride, dicyclohexylcarbodiimide, 4-dimethylaminopyridine, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and sulfoxide; in step S113, the cyclization reaction temperature is 25°C, and the reaction time is 30 min to 60 min.
[0027] Compared with existing technologies, the technical advantages achieved by this solution are as follows: In S113, organic solvents such as dichloromethane and tetrahydrofuran are used. These solvents possess excellent solubility and chemical stability, effectively dissolving the precursor and providing a uniform reaction environment for the cyclization reaction. This promotes efficient contact between the cyclization catalyst and the precursor, avoiding incomplete cyclization caused by uneven local concentrations. Simultaneously, no side reactions occur with the precursor or catalyst, ensuring reaction purity. The cyclization catalyst is selected from highly reactive reagents such as phosphorus tribromide and phosphorus oxybromide, precisely activating the reaction sites in the precursor and efficiently driving the intramolecular cyclization reaction. This rapidly forms a stable five-membered ring structure of valine N-thiocarboxylic anhydride, ensuring the completeness of the cyclization reaction and the uniformity of the product structure. The cyclization reaction temperature is set at 25℃. This mild condition maintains catalyst activity while avoiding precursor degradation or side reactions caused by high temperatures, eliminating the need for complex temperature control equipment and reducing operational difficulty and energy consumption. The reaction time is controlled between 30 min and 60 min. This ensures that the cyclization reaction proceeds fully and avoids incomplete cyclization due to too short a time. It also prevents product deterioration caused by an excessively long reaction time, thus achieving a balance between cyclization reaction efficiency and product quality.
[0028] In one embodiment of the present invention, in step S114, the washing liquid is selected from at least one of a saturated sodium chloride solution and water; in step S114, the recrystallization solvent is selected from at least one of dichloromethane, tetrahydrofuran, diethyl ether, acetonitrile, ethyl acetate, methyl tert-butyl ether, n-butanol, and n-hexane.
[0029] Compared with existing technologies, the technical effects achieved by this solution are as follows: In S114, at least one of saturated sodium chloride solution and water is used as the washing liquid. The saturated sodium chloride solution can reduce the solubility of the cyclization product in the aqueous phase through the salting-out effect, reducing product loss. At the same time, it can efficiently remove inorganic impurities, residual catalysts, and some water-soluble byproducts generated in the cyclization reaction. Water can further wash away residual salts and small molecule impurities. The synergistic effect of the two can deeply purify the cyclization solution, laying the foundation for subsequent purification steps. The recrystallization solvent is selected from at least one of dichloromethane, tetrahydrofuran, and other solvents. These solvents have suitable solubility characteristics, which can fully dissolve the crude product when heated and cause the valine N-thiocarboxylic anhydride monomer to precipitate in crystal form when cooled, while trace impurities remain in the solvent. Recrystallization can significantly improve the purity and crystallinity of the monomer, avoiding the impact of insufficient monomer purity on the controllability of subsequent polymerization reactions. Attached Figure Description
[0030] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the accompanying drawings used in the description of the embodiments or the prior art will be discussed below. Obviously, the technical solutions described in conjunction with the accompanying drawings are only some embodiments of the present invention. For those skilled in the art, other embodiments and their accompanying drawings can be obtained based on the embodiments shown in these drawings without creative effort.
[0031] Figure 1 This is the 1H NMR spectrum of the valine N-thiocarboxylic anhydride monomer of the present invention. Detailed Implementation
[0032] The technical solutions of various embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments described in the present invention, all other embodiments obtained by those skilled in the art without creative effort are within the scope of protection of the present invention.
[0033]
Example 1
[0034] S100. Add 10 mL of n-hexane as an organic solvent to the reaction flask, then add 53 mg (0.334 mmol) of the valine N-thiocarboxylic anhydride prepared above, and then add 0.08 mL of n-hexylamine in n-hexane (concentration 0.18 mol / L). The molar ratio of valine N-thiocarboxylic anhydride to initiator is 23:1. Shake thoroughly to mix evenly and obtain the first reactant. S200. The first reactant is placed in a constant temperature oil bath at 30°C and reacted continuously for 24 hours under a 40W ultrasonic environment to obtain the second reactant. S300: The second reactant is added to diethyl ether to elute unreacted monomers and precipitate. The precipitate is collected by filtration and vacuum dried to constant weight to obtain a homopolymer of amino acids (polyvaline) with valine residues as repeating units, with a yield of 98%. The product is then analyzed by SEC and other methods. Figure 1 The NMR characterization shown indicates that the product has a molecular weight of 2.3 kDa and a molecular weight distribution of 1.15.
[0035]
Example 2
[0036]
Example 3
[0037]
Example 4
[0038]
Example 5
[0039]
Example 6
[0040]
Example 7
[0041]
Example 8
[0042] Comparative Example 1 The preparation method for this comparative example is the same as in Example 1, except that in S100, the molar ratio of valine N-thiocarboxylic anhydride to initiator is 10:1.
[0043] Comparative Example 2 The preparation method for this comparative example is the same as in Example 1, except that in S100, the molar ratio of valine N-thiocarboxylic anhydride to initiator is 400:1.
[0044] Comparative Example 3 The preparation method for this comparative example is the same as in Example 1, except that in S200, ultrasound assistance was not used (i.e., no ultrasound environment).
[0045] Comparative Example 4 The preparation method for this comparative example is the same as in Example 1, except that the ultrasonic power in S200 is 10W.
[0046] Comparative Example 5 The preparation method for this comparative example is the same as in Example 1, except that the reaction temperature in S200 is 5°C.
[0047] Comparative Example 6 The preparation method for this comparative example is the same as in Example 1, except that the reaction temperature in S200 is 70°C.
[0048] Comparative Example 7 The preparation method for this comparative example is the same as in Example 1, except that valine N-thiocarboxylic anhydride is replaced with valine N-carboxylic anhydride (NCA).
[0049] Table 1
[0050] According to the test results in the table above, the polyvaline provided in Examples 1-8 has a number-average molecular weight in the range of 2.0 kDa-29.8 kDa, a molecular weight distribution below 1.2, and a yield above 95%. It also exhibits good solubility in dilute hydrochloric acid, demonstrating excellent controllable synthesis and product performance. Compared to the comparative examples, the examples show a narrower molecular weight distribution, higher yield, better solubility, and significantly improved overall performance. Examples 1, 2, and 3, along with Comparative Examples 1 and 2, show that when the molar ratio of valine N-thiocarboxylic anhydride to the initiator is controlled within the range of (20-300):1, the molecular weight of the product can be precisely controlled, and the molecular weight distribution remains within a narrow range. In Comparative Example 1, when the ratio is below 20:1, the product molecular weight is smaller, the distribution is slightly wider, and precipitation loss is greater. In Comparative Example 2, when the ratio is above 300:1, the molecular weight distribution becomes significantly wider, and the controllability of polymerization decreases. Examples 1, 4, and 5, and Comparative Examples 3 and 4, demonstrate that the introduction of ultrasound-assisted technology is crucial for the polymerization reaction. In Comparative Examples 3 and 4, without an ultrasound environment or with an ultrasound power below 20W, the molecular weight distribution of the product significantly broadened, and the yield decreased substantially. Ultrasonic power between 20W and 100W effectively ensured the controllability and efficiency of the polymerization reaction. Examples 1, 6, and 7, and Comparative Examples 5 and 6, show that a reaction temperature of 15℃-50℃ is the suitable range for ensuring product performance. In Comparative Example 5, temperatures below 15℃ led to a decrease in yield and a broadening of the molecular weight distribution. In Comparative Example 6, temperatures above 60℃ resulted in a broadening of the molecular weight distribution and a decrease in solubility. Examples 1 and Comparative Example 7 show that using valine N-thiocarboxylic anhydride as a monomer has significant advantages over traditional valine N-carboxylic anhydride in terms of molecular weight control, yield, and solubility. Traditional NCA monomers, due to their poor stability, resulted in products with low molecular weight, broad distribution, low yield, and poor solubility. Furthermore, in Example 8, after replacing the organic solvent with methyl tert-butyl ether, the product performance remained stable, indicating that the organic solvent selected in this invention has good compatibility, further demonstrating the flexibility and reliability of this synthesis method.
[0051] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above, and that the invention can be implemented in other specific forms without departing from its spirit or essential characteristics. Therefore, the embodiments should be considered illustrative and non-limiting in all respects. The scope of the invention is defined by the appended claims, not by the foregoing description, and thus all variations falling within the meaning and scope of equivalents of the claims are intended to be included within the invention. No reference numerals in the claims should be construed as limiting the scope of the claims.
[0052] Furthermore, it should be understood that although this specification describes embodiments, not every embodiment contains only one independent technical solution. This narrative style is merely for clarity. Those skilled in the art should consider the specification as a whole, and the technical solutions in each embodiment can also be appropriately combined to form other embodiments that can be understood by those skilled in the art.
Claims
1. A method for synthesizing polyvaline, characterized in that, Includes the following steps: S100. Add valine N-thiocarboxylic anhydride, initiator and organic solvent to the reactor, mix and stir to obtain the first reactant; S200. The first reactant is subjected to an ultrasonic reaction to obtain a second reactant; S300. The second reactant is precipitated in an extractant, filtered, and vacuum dried to obtain polyvaline.
2. The method for synthesizing polyvaline according to claim 1, characterized in that, The initiator is selected from at least one of amines containing C2-C9 aliphatic hydrocarbon functional groups.
3. The method for synthesizing polyvaline according to claim 1, characterized in that, In S100, the molar ratio of valine N-thiocarboxylic anhydride to initiator is (20-300):1; In S100, the organic solvent is selected from at least one of n-hexane, n-heptane, methanol, ethanol, and petroleum ether.
4. The method for synthesizing polyvaline according to claim 1, characterized in that, In S200, the temperature of the ultrasonic reaction is 15℃-50℃; In S200, the ultrasonic environment is 20W-100W.
5. The method for synthesizing polyvaline according to claim 1, characterized in that, The extractant is selected from at least one of dichloromethane, tetrahydrofuran, diethyl ether, acetonitrile, ethyl acetate, methyl tert-butyl ether, and n-butanol.
6. The method for synthesizing polyvaline according to any one of claims 1-5, characterized in that, The valine N-thiocarboxylic anhydride is prepared by the following steps: S111. Valine, sodium hydroxide, 2-((ethoxythiocarbonyl)thio)acetic acid and water are placed in a reactor and reacted to obtain a pre-precursor. S112. The pre-precursor is subjected to acidification, extraction, washing, drying, filtration and vacuum concentration in sequence to obtain the precursor; S113. Dissolve the precursor in an organic solvent, add a cyclization catalyst, and carry out a cyclization reaction to obtain a cyclization solution; S114. The cyclized solution is sequentially washed, dried, filtered, concentrated under reduced pressure, and recrystallized to obtain the valine N-thiocarboxylic anhydride.
7. The method for synthesizing polyvaline according to claim 6, characterized in that, In S111, valine, sodium hydroxide, and 2-((ethoxythiocarbonyl)thio)acetic acid are added in a molar ratio of (0.8-1.2):(1.8-2.5):(0.8-1.2). In S111, the reaction temperature is 25℃ and the reaction time is 48h-96h.
8. The method for synthesizing polyvaline according to claim 6, characterized in that, In S112, acidify to a pH of 1-2; In S112, the extractant is selected from at least one of dichloromethane, tetrahydrofuran, diethyl ether, acetonitrile, ethyl acetate, methyl tert-butyl ether, and n-butanol; In S112, the washing solution is selected from at least one of an aqueous citric acid solution and a saturated sodium chloride solution.
9. The method for synthesizing polyvaline according to claim 6, characterized in that, In S113, the organic solvent is selected from at least one of dichloromethane, tetrahydrofuran, diethyl ether, acetonitrile, ethyl acetate, methyl tert-butyl ether, and n-butanol; In S113, the cyclization catalyst is selected from at least one of phosphorus tribromide, phosphorus oxybromide, phosphorus trichloride, dicyclohexylcarbodiimide, 4-dimethylaminopyridine, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, and sulfoxide. In S113, the cyclization reaction temperature is 25℃ and the reaction time is 30min-60min.
10. The method for synthesizing polyvaline according to claim 6, characterized in that, In S114, the washing liquid is selected from at least one of a saturated sodium chloride solution and water; In S114, the solvent for recrystallization is selected from at least one of dichloromethane, tetrahydrofuran, diethyl ether, acetonitrile, ethyl acetate, methyl tert-butyl ether, n-butanol, and n-hexane.