Pyrimidine-based ionic liquids, their preparation methods and their applications

Abstract

The present invention relates to the field of ionic liquids. Specifically, it relates to a pyrimidine-based ionic liquid, a preparation method thereof, and an application thereof. The name of the pyrimidine-based ionic liquid is [A]X, and the structural formula of the pyrimidine-based ionic liquid is shown as follows: #imgabs0# wherein, [A] is derived from an amino alcohol compound; R1 represents a C1-C4 alkyl group, and R2 represents hydrogen or a hydroxyl group. The pyrimidine-based ionic liquid has the advantages of low viscosity, stability to air and water, good compatibility with solutes, and excellent solubility, and can be widely applied in industries, especially in the biomedical field.

Description

Technical Field

[0001] The present invention relates to the field of ionic liquids, and in particular, to a pyrimidine-based ionic liquid, a preparation method thereof, and an application thereof. Background Art

[0002] Solvents are the basis of chemistry, biology, chemical engineering, and biotechnology, and the emissions of solvents are also huge. Specifically, the emissions of solvents account for about two-thirds of the total industrial emissions. Traditional organic solvents are volatile and easily volatilize into the atmosphere, causing many negative impacts, including climate change, deterioration of urban air quality, and human diseases. Ionic liquids are recognized as designable solvents. By designing ion pairs, the eutectic point of the solvent and the solute can be reduced. The ion pairs formed between the solvent and the solute are mainly bound by ionic interactions and hydrogen bonds rather than covalent bonds, thereby changing the physical and chemical properties of the active ingredient without changing its pharmacological activity.

[0003] The most important characteristics of ionic liquids are non-volatility, non-flammability, high thermal stability, good solubility, and surface activity. They are currently recognized as green solvents that can replace organic solvents. Due to the adjustable nature of ionic liquids, that is, by designing ion pairs, the viscosity, hydrophilicity, polarity, density, and acidity / basicity of ionic liquids can be regulated, so they have a wider range of applicability. Therefore, the replacement of traditional solvents by ionic liquids has always been a hot topic and research direction in academia and industry. The EU REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals) regulation and its list of restricted substances aim to improve safety and protect the environment, and gradually phase out hazardous chemicals.

[0004] Functionalized ionic liquids refer to task-specific ionic liquids. In addition to having the basic characteristics of ionic liquids such as excellent stability, low volatility, good substrate compatibility, and structural designability, the functional groups contained in the structure make ionic liquids special reagents for achieving specific task goals, in order to reduce the negative impacts on the environment and health.

[0005] Low solubility is a characteristic of most active pharmaceutical ingredients (APIs). In the modern pharmaceutical field, on the one hand, ionic liquids, as solvents, provide solutions to avoid problems such as polymorphic transformation and poor solubility of solid drugs; on the other hand, ionic liquids can act as active components to form a new drug delivery system of APIs and ionic liquids (API-ILs), which can effectively control the stability and bioavailability of drug mixtures.

[0006] As is well known, the main obstacles hindering the industrial application of ionic liquid technology are high viscosity, low water and air stability. Most of the ionic liquids synthesized so far have high viscosity, low ionic conductivity and low diffusion coefficient. Even at high temperatures, the diffusion coefficient of the constituent ions is several orders of magnitude lower than that of water. At a certain temperature, the viscosity of ionic liquids decreases with the increase of water content. However, as a polar solvent, water can also form hydrogen bonds as donors and acceptors, thus weakening or even destroying the intermolecular and intramolecular hydrogen bonds in the system. Especially when the mole fraction of water exceeds 0.5 - 0.8, strong hydrogen bonds are formed between water molecules and ions, disrupting the ion pair equilibrium.

[0007] According to a report in the journal Science in 2003, theoretically, hundreds of millions of ionic liquid species can be combined. Therefore, screening ion pairs that can be used to perform specific tasks is an important challenge and the primary task in the synthesis of functional ionic liquids.

[0008] Chinese Patent CN108912054 A discloses a mercapto-pyrimidine-based anti-corrosive ionic liquid, its preparation method and application. This is an ionic liquid for specific tasks in the lubricant industry, prepared into an ionic liquid by a 4-step synthesis method such as esterification and anion exchange, or a 5-step synthesis for an industrial lubricant. The synthesis process is complex: it requires removing precipitates, removing solvents, and processes such as nitrogen protection and vacuum drying. Both the synthesis substrates and products are not suitable for biomedical applications and do not conform to the atom-economic reaction process.

[0009] Chinese Patent CN 115298190 A discloses a choline-based ionic liquid solvent. The synthesis process requires the volatile organic solvent chloroform and needs to be synthesized under a nitrogen atmosphere. It also requires the use of hydrochloric acid for phase separation, and pure water is needed to wash the hydrochloric acid and further remove chloroform and water. Due to hydrophobicity, it becomes turbid when encountering water and requires organic solvents such as isopropanol and sorbitan monolaurate for solubilization and co-emulsification. Therefore, it cannot completely replace organic solvents.

[0010] Therefore, the objective of the present invention is to develop a functionalized ionic liquid solvent designed for specific tasks in biomedicine to replace traditional volatile organic solvents that pose threats to the environment and health. Summary of the Invention

[0011] The present invention provides a pyrimidine-based ionic liquid, its preparation method and its application, aiming to improve the problems of high viscosity of ionic liquids, as well as poor stability to water, air and solute compatibility.

[0012] The present invention is implemented as follows:

[0013] In a first aspect, an embodiment of the present invention provides a pyrimidine-based ionic liquid, and the name of the pyrimidine-based ionic liquid is [A]X, where [A] represents the cationic part and X represents the anionic part; the structural formula of the pyrimidine-based ionic liquid is shown as follows:

[0014] Among them, [A] is derived from an amino alcohol compound, R1 represents a C1-C4 alkyl group, and R2 represents hydrogen or a hydroxyl group.

[0015] In a second aspect, an embodiment of the present invention provides a preparation method of the above pyrimidine-based ionic liquid, including: mixing and dissolving the raw materials for forming the cation [A] and the raw materials for forming the anion X.

[0016] In a third aspect, an embodiment of the present invention provides an application of the above pyrimidine-based ionic liquid as a solvent for dissolving low-water-soluble APIs.

[0017] The beneficial effects of the present invention are as follows: The present invention screens and designs a new pyrimidine-based ionic liquid, which has the advantages of low viscosity, stability to air and water, good compatibility with solutes, and excellent dissolution ability, and can be widely used in industry, especially in the field of biomedicine. Description of the Drawings

[0018] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments will be briefly introduced below. It should be understood that the following drawings only show some embodiments of the present invention, and therefore should not be regarded as limiting the scope. For those of ordinary skill in the art, other related drawings can be obtained based on these drawings without creative efforts.

[0019] Figure 1 is the nuclear magnetic spectrum of the pyrimidine-based ionic liquid provided in Example 1 of the present invention;

[0020] Figure 2 is the ultraviolet-visible spectrum of cytochrome C in Application Example 8 of the present invention;

[0021] Figure 3 is the reaction energy barrier of Experimental Example 1 and Comparative Example 1 of the present invention;

[0022] Figure 4 is the thermodynamic energy of the cytochrome C conformation in Example 8 of the present invention. Detailed Embodiments

[0023] To make the objectives, technical solutions, and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below. For those not specifying specific conditions in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. For reagents or instruments not indicating the manufacturer, they are all conventional products that can be obtained through commercial purchase.

[0024] The following specifically describes a pyrimidine-based ionic liquid provided by the embodiments of the present invention, its preparation method, and applications.

[0025] According to the foregoing description, it can be known that the high viscosity of ionic liquids is a technical problem that hinders their wide application. To solve the technical problem of the high viscosity of ionic liquids, the embodiments of the present invention start from the design of hydrated ionic liquids. The stability of hydrated ionic liquids depends on the interactions between cations and anions, as well as between ions and water. The smaller the ion and the more charge it carries on the surface, the stronger the interaction between ions, and the more stable the hydrated ionic liquid. Among them, the role of anions is crucial because the interaction between water and anions is stronger, forming a "anion…HOH…anion" hydrogen bond structure in a 1:2 ratio, which dominates the regulation of the structural stability of hydrated ionic liquids. On the other hand, the hydrogen bond structure formed between water and anions is crucial for the activity and stability of proteins. Therefore, in terms of developing a chiral functionalized ionic liquid solvent designed to achieve specific task objectives in biomedicine, screening a negatively charged biomolecule is a feasible solution.

[0026] The embodiments of the present invention design through a series of ion pairs and their molar combination ratios, including screening a larger number of ion pairs using theoretical and computational chemistry methods. It is observed that the liquid temperature window period (ΔT) of the ionic liquid shifts from offset to expansion, and the water content increases from 0.1 to more than 0.8 mole fraction, ultimately obtaining a pyrimidine-based functionalized hydrated ionic liquid solvent with low viscosity, stable to water and air, and having good compatibility with solutes.

[0027] Molecular simulation experiments found that strong hydrogen bonds are formed between the selected ion pairs, and the bond energy of these hydrogen bonds is much lower than that of covalent bonds. Therefore, the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention has a self-assembled structure driven by non-covalent bonds at normal temperature and pressure. That is, due to the strong coordination ability resulting from the special structure of anions, the formation of strong intermolecular hydrogen bonds is the main driving force for molecular recognition and self-assembly, and this strong electrostatic force is sufficient to offset the weakening or destruction of intermolecular hydrogen bonds by the polarity of water, ultimately forming a thermodynamically stable pyrimidine-based ionic liquid [A]X. It was unexpectedly found that the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention naturally has strong solubility and can completely replace traditional organic solvents for dissolving typical low-water-soluble APIs.

[0028] An embodiment of the present invention provides a pyrimidine-based ionic liquid, and the name of the pyrimidine-based ionic liquid is [A]X, where [A] represents the cationic part and X represents the anionic part; the structural formula of the pyrimidine-based ionic liquid is as follows:

[0029] Among them, [A] is derived from an amino alcohol compound; R1 represents a C1-C4 alkyl group.

[0030] Furthermore, [A] is derived from an amino alcohol compound, including 2-amino-2-methyl-1-propanol, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-hydroxymethyl-1,3-propanediol, ethanolamine, diethanolamine, triethanolamine, N,N,N-trimethylglycine, choline, choline chloride, phosphatidylcholine, hydrogenated phosphatidylcholine, phosphatidylethanolamine, and cytidine diphosphate choline. Specifically, its structural formula is selected from any one of the following groups:

[0031]

[0032]

[0033] Preferably, [A] is derived from 2-amino-2-methyl-1-propanol, choline chloride, and hydrogenated phosphatidylcholine, and is selected from any one of the following structural formulas:

[0034]

[0035] Furthermore, R1 in X is further preferably a C1-C3 alkyl group, such as methyl, ethyl, and n-propyl, etc. In the embodiments of the present invention, X includes but is not limited to any one of the following groups:

[0036]

[0037] It should be noted that the above groups are examples of the embodiments of the present invention and are not limited to the above groups.

[0038] Specifically, the molar ratio of [A] to X is (1:1) to (4:1); for example, 1:1, 1.5:1, 2:1, 2.5:1, 3:1, 3.5:1, and 4:1, etc., any value between (1:1)-(4:1), and preferably (2:1) to (3:1).

[0039] The pyrimidine-based ionic liquid is a hydrated ionic liquid; preferably, the pyrimidine-based ionic liquid is an anion chiral functionalized ionic liquid.

[0040] Furthermore, an embodiment of the present invention provides a preparation method of the above pyrimidine-based ionic liquid, including: mixing and dissolving the raw materials for forming the cation [A] and the raw materials for forming the anion X.

[0041] Among them, the entire preparation process is carried out under non-vacuum conditions (such as normal temperature and pressure). Raw materials forming cation [A] and raw materials forming anion X are dissolved with water. The temperature for mixed dissolution is 30 - 50 °C, and the time is 10 - 30 min. Alternatively, no solvent is added during the preparation of pyrimidine-based ionic liquids, and the two raw materials are directly mixed to form the required ionic liquid.

[0042] The pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention is designed according to the principles of green chemistry. It is synthesized from non-toxic, harmless, natural, and renewable raw materials, does not produce cytotoxicity, and is suitable for biomedical applications. It is synthesized in one step under normal temperature and pressure without solvent or only with water as the solvent, and no waste is generated during the synthesis process, achieving zero emissions in industrial production. It conforms to the definition of green chemistry by the United Nations Environment Programme in 1996: using chemical technologies and methods to reduce or eliminate the production and application of raw materials, products, by-products, solvents, and reagents that are harmful to human health or the environment.

[0043] The pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention can be used as a solvent for dissolving low-water-soluble APIs and biomass. It has excellent solubility in dissolving low-water-soluble APIs and can stably dissolve. Among them, the low-water-soluble API has a solubility less than 3 g at 20 °C; preferably less than 1 g, more preferably less than 0.001 g; for example, the low-water-soluble API includes but is not limited to ibuprofen, salicylic acid, azelaic acid, antibacterial fat, retinol, retinoic acid, and any one of lignin, vanillin, gallic acid, and cytochrome C.

[0044] It should be understood that the solubility of a solvent is usually solute-specific, and the solubility is exponentially related to the solvent concentration, that is, the solubility of any solute depends to a large extent on the mole fraction (xi) of the ionic liquid solvent [A]X. The pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention, as a solvent system composed of a series of ionic liquids, may have a very different and wide range of solute applicability. However, the test range of the embodiments of the present invention is limited. Therefore, ibuprofen, salicylic acid, azelaic acid, antibacterial fat, retinol, retinoic acid, and lignin, vanillin, gallic acid, and cytochrome C listed in the application examples of the present invention are only used as model compounds to test the solvent performance of the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention, and should not be regarded as a limitation of the scope.

[0045] In summary, the pyrimidine-based ionic liquid provided by the embodiments of the present invention has the following characteristics:

[0046] (1) Green process: The pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention is synthesized by a green process with chiral natural products as substrates and water as a solvent at normal temperature and pressure. It has the characteristics of general ionic liquids, such as almost negligible low vapor pressure, that is, non-volatile characteristics, and can replace traditional volatile organic solvents. Among them, the anion X is pyrimidine carboxylic acid, and the cation [A] is amino alcohol. Due to the absence of extractable hydrogen in its molecular structure, it has special photochemical stability and is a low-volatile organic compound additive in the biomedical process and a chiral ligand for the synthesis of chiral pharmaceutical intermediates.

[0047] (2) Atom economy: The acid-base neutralization reaction is a typical 100% atom economy reaction. In the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention, the pKa value of the anion part (about 1.3 - 3.14) is much smaller than the pKa value of the cation part (about 8.0 - 9.8). Therefore, the [A]X molecule as the reaction substrate can smoothly generate the ionic liquid [A]X through the acid-base neutralization reaction at normal temperature and pressure with a yield of 100%. That is, the reaction process for preparing the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention conforms to the classical acid-base theory and has complete atom economy.

[0048] (3) Fast reactivity: Most of the ionic liquids reported so far require multi-step synthesis with a long reaction time. At the same time, organic solvents are required as reaction media or need to be washed and purified, which not only wastes resources but also pollutes the environment. The pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention can be synthesized in one step at normal temperature and pressure without dehydration or purification. The specific steps are as follows: Dissolve the raw materials forming the cation [A] and the raw materials forming the anion X with water, and stir conventionally for 10 - 30 min at 30 - 50 °C until completely dissolved; or the raw materials forming the cation [A] and the raw materials forming the anion X can be mixed without a solvent and heated to 80 - 120 °C for one-step synthesis, but the required time is longer. Therefore, it is preferably synthesized rapidly by a one-step direct method with water as a solvent.

[0049] (4) Low viscosity at room temperature: Most of the reported ionic liquids have viscosities 1 - 3 orders of magnitude higher than those of traditional organic solvents, which has become one of the important factors hindering the industrial application of ionic liquids. Since the present invention adopts a synthetic route of hydrated ionic liquids for de novo synthesis, and the pyrimidine carboxylic acid anion of the anion X has a flexible structure with R and S configuration interconversion, the delocalized electrons on the pyrimidine ring increase the ion mobility and ionic conductivity, thus endowing the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention with natural low viscosity, creating conditions for its industrial application in the biomedical field.

[0050] (5) Stability and Solute Compatibility: In the ionic liquid [A]X, the anion X is derived from the products of halophilic bacteria in desert salt lakes and is a biological protection factor on which microorganisms rely for survival in extreme environments. For example, 2-methyl-1,4,5,6-tetrahydropyrimidinecarboxylic acid has two isomers, namely 2-methyl-1,4,5,6-tetrahydropyrimidinecarboxylic acid and 2-methyl-3,4,5,6-tetrahydropyrimidinecarboxylic acid, which exist in three zwitterionic states in aqueous solution. This zwitterionic compound contains a carboxyl group and two amino groups that bind to water through strong hydrogen bonds, causing more water molecules to be in the bound water state and restricting the solvation effect of water. At the same time, strong hydrogen bonds and multi-hydrogen bonds are formed between the carboxylate anion and the cation, and this strong electrostatic force further counteracts the weakening or destruction of the intermolecular hydrogen bonds by the polarity of water. This is the molecular basis for the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention to have a high water content, and its water content can be as high as more than 0.90 mole fraction. Therefore, the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention is stable to water and air and has good compatibility with solutes, and thus has practical application value.

[0051] The pyrimidine carboxylic acid acting as the X anion has unique tautomers and zwitterionic states. That is, the 2-methyl-1,4,5,6-tetrahydropyrimidinecarboxylic acid and 2-methyl-3,4,5,6-tetrahydropyrimidinecarboxylic acid isomers (I, II) exist in three zwitterionic states (III, IV, V) in aqueous solution:

[0052]

[0053] (6) Strong Solubility: The hydrogen bond of the ionic liquid is a very important non-covalent interaction, which significantly affects the physical and chemical properties and solubility of the ionic liquid. Due to the structural asymmetry of the pyrimidine-based ionic liquid [A]X system provided by the embodiments of the present invention, where the anion X component exists in three zwitterionic states (III, IV, V) in aqueous solution, the carboxylate anion and amino cation in the pyrimidine carboxylic acid molecule can both bind to the surrounding water molecules to form strong hydrogen bonds and multi-hydrogen bonds, endowing the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention with strong solubility.

[0054] The pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention exhibits neutral to basic and medium polarity in terms of physical and chemical properties. Its dielectric constant is significantly lower than that of water and is close to that of organic solvents such as benzene, toluene, carbon tetrachloride, chloroform, ether, ethanol, etc., which means it shows the characteristics of a hydrophilic and highly soluble ionic liquid solvent and can be mixed with water in any proportion; its surface tension is between that of water and traditional surfactants such as anionic surfactant N-acyl amino acid, indicating that the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention has the characteristics of general surfactants. This characteristic can greatly change the environmental pollution and health damage caused by organic solvents and surfactants in the fields of biomedicine, chemical engineering, and daily chemicals.

[0055] (7) Biological functionality: In the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention, the anion part X is a pyrimidine carboxylic acid which is a bio-protective factor of natural origin and can be classified as an amino acid derivative in chemistry. Therefore, it has characteristics such as better environmental friendliness, biocompatibility, and biodegradability; pyrimidine carboxylic acid has R and S chiral configurations, thus being able to provide a stable chiral center, which is beneficial to stabilizing biological macromolecules such as proteins, nucleic acids, and DNA bases, and belongs to an anion chiral-functionalized bio-ionic liquid solvent. Compared with traditional organic solvents, it is more suitable for biomedical applications.

[0056] The pyrimidine carboxylic acid serving as the X anion part has a negatively charged carboxyl group connected to a pyrimidine ring containing a delocalized positive charge and is a chiral molecule with R and S enantiomers, providing a stable chiral center:

[0057]

[0058] Furthermore, in the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention, since the carboxyl group of the anion X can form hydrogen bonds with the amino group of proteins, it has unique behavior in regulating the stability of proteins. This is because in the higher-order structure of bioactive proteins, the binding forces between subunits are mainly hydrogen bonds and ionic bonds. Therefore, the type of anions present in the ionic liquid plays a key role in the activity and stability of proteins dissolved in the ionic liquid. This aromatic X anion part largely contributes to the characteristics of the [A]X system in dissolving and stabilizing proteins, constituting the structural basis of the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention.

[0059] Therefore, compared with the prior art, the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention has direct and obvious technical effects of reducing or stopping the consumption of natural resources and being environmentally friendly, and can completely replace organic solvents and surfactants in application examples.

[0060] Cellulose is a biomass resource that is inexhaustible and renewable in nature. However, cellulose is a highly cross-linked aromatic polymer and thus has poor solubility. In Application Example 5 of the present invention, the solubility of lignin at normal temperature and pressure reaches 15%, and it can stably dissolve at room temperature for at least 72 hours.

[0061] Furthermore, the solubility and conformation of cytochrome C in the ionic liquid [A]X were studied. Cytochrome C is a classical laboratory model protein for studying the protein folding mechanism. It can undergo reversible redox reactions in living organisms. The iron ion in its iron porphyrin center exists in the reduced state Fe 2+ and the oxidized state Fe 3+ and transfers electrons from cytochrome C reductase to cytochrome C oxidase. During the conversion process, multiple conformational conversions occur, and its conformation is easily affected by various factors such as the environment, interaction with ligands, pH, and temperature. The redox activity of cytochrome C depends on its correct folding in solution. On the one hand, due to the hydrophilicity of the pyrimidine-based ionic liquid solvent [A]X provided in the embodiments of the present invention, it can be mixed with water in any proportion, so it becomes a good solvent for proteins; on the other hand, the hydrophilic structuring effect of the pyrimidine carboxylate anion makes more water molecules in the bound water state, weakening the adverse effects of the solvation of water on the protein structure and activity.

[0062] In summary, the pyrimidine-based ionic liquid [A]X provided in the embodiments of the present invention belongs to a hydrophilic, anion chiral-functionalized biohydrated ionic liquid solvent, and is a green solvent system designed to achieve specific task goals in biomedicine. It is synthesized by a green process with chiral natural products as substrates and water as a solvent at normal temperature and pressure, is stable to air, water, and temperature, and is compatible with solutes. It is suitable for the dissolution and preservation of low-water-soluble APIs and biological macromolecules in the field of biomedicine, or as a chiral-functionalized ionic liquid solvent or chiral intermediate in biomedical processes.

[0063] The raw materials provided in the embodiments of the present invention are as follows: 2-methyl-1,4,5,6-tetrahydropyrimidinecarboxylic acid (100% Merck), 2-amino-2-methyl-1-propanol, 2-amino-2-methyl-1,3-propanediol, 2-amino-2-hydroxymethyl-1,3-propanediol (95 - 100% Angus), hydrogenated phosphatidylcholine (94% Lipoid), choline chloride (analytical grade, Sinopharm), ibuprofen (98.5% J&K), salicylic acid, lauric acid, palmitic acid, stearic acid (analytical grade, Xilong), glyceryl caprylate, glyceryl laurate (100% Indus), lignin, cytochrome C, carnitine, N,N,N-trimethylglycine (95 - 99% Macklin), γ-aminobutyric acid (99% Geno Biotech), aspartic acid, glutamic acid, arginine, glycine, tryptophan (USP, Hydrion), azelaic acid, retinal, retinoic acid, vanillin, gallic acid (98 - 99% Aladdin).

[0064] The performance test method is as follows:

[0065] Method for measuring physical properties: The viscosity (η, mPa·s) was measured by the direct measurement method using a digital display viscometer (NDJ-8S); the conductivity (Λ, mS / cm) was measured by the direct measurement method using a conductivity meter (DDS-307A); the dielectric constant (ε) was measured using an impedance analyzer (TH-2839); the surface tension (σ, mN / m) was measured using a surface tension meter (ThetaFlex); the pH was measured by the direct measurement method using a pH meter. The actual test temperature was 25 - 30 °C.

[0066] Method for measuring cold resistance, heat resistance and liquid temperature window period (ΔT): (1) Cold resistance: Pre-adjust the refrigerator to (-8 °C ± 1 °C) or (0 °C ± 1 °C), and place one bottle of the sample in the refrigerator. After 24 hours, take it out, and after restoring to room temperature, visually observe. If there is no obvious difference in properties compared with before the test, it is considered stable. (2) Heat resistance: Pre-adjust the constant temperature incubator to (40 °C ± 1 °C), and place one bottle of the sample in the constant temperature incubator. After 24 hours, take it out, and after restoring to room temperature, visually observe. If there is no obvious difference in properties compared with before the test, it is considered stable.

[0067] The following specifically describes a pyrimidine-based ionic liquid, its preparation method and its application provided by the present invention in combination with specific embodiments.

[0068] Examples 1 - 4

[0069] Examples 1 - 4 all provide a pyrimidine-based ionic liquid, and its structural formula is as follows:

[0070]

[0071] Examples 1 - 4 all provide a preparation method of a pyrimidine-based ionic liquid, including: successively adding the raw material 2-amino-2-methyl-1-propanol for forming the cation [A] and the raw material 2-methyl-1,4,5,6-tetrahydropyrimidinecarboxylic acid for forming the anion X into a small amount of water according to the molar ratio shown in Table 1, stirring at 30 °C - 50 °C for 10 - 30 minutes until completely dissolved, and supplementing water to a total amount of 100%, thus obtaining the pyrimidine-based ionic liquid [A]X of Examples 1 - 4.

[0072] Among them, the molar ratio is rounded to an integer according to rounding rules.

[0073] Furthermore, the physical and chemical properties of the pyrimidine-based ionic liquids prepared in Examples 1 - 4 were detected, and the detection results are shown in Table 1. The results show that the pyrimidine-based ionic liquids [A]X obtained in Examples 1 - 4 have the characteristics of low viscosity, low surface tension, high ionic conductivity, high water content, alkalinity and polarity.

[0074] Further, nuclear magnetic resonance characterization was performed on the pyrimidine-based ionic liquid of Example 1 ( Figure 1 ). According to Figure 1 , the chemical shifts of the pyrimidine carboxyl group and the protons on the ring of the anion part [A] and the characteristic resonance peaks of the methyl protons, as well as the chemical shifts and characteristic resonance peaks of the hydroxyl group, amino group and methyl protons of the anion part X, can be clearly identified, indicating that the pyrimidine-based ionic liquid required in the examples of the present invention was prepared.

[0075] Table 1 Composition and physicochemical properties of pyrimidine-based ionic liquids [A]X of Examples 1-4

[0076]

[0077] Examples 5-8

[0078] Examples 5-8 all provide a pyrimidine-based ionic liquid, and its structural formula is as follows:

[0079]

[0080] Examples 5-8 all provide a preparation method of a pyrimidine-based ionic liquid, including: successively adding choline chloride as the raw material for forming the cation [A] and 2-methyl-1,4,5,6-tetrahydropyrimidine carboxylic acid as the raw material for forming the anion X into a small amount of water according to the molar ratio shown in Table 2, and stirring conventionally at 30-50 °C for 10-30 min until completely dissolved, and then adding water to make the total liquid volume 100%, thus obtaining the pyrimidine-based ionic liquid [A]X of Examples 5-8.

[0081] Among them, the molar ratio is rounded to an integer according to the rounding rule.

[0082] Further, physicochemical property detection was performed on the pyrimidine-based ionic liquids prepared in Examples 5-8, and the detection results are shown in Table 2. The results show that the pyrimidine-based ionic liquids [A]X obtained in Examples 5-8 have low viscosity, low surface tension, high ionic conductivity and high water content, as well as the properties of being neutral, polar and hydrophilic.

[0083] Table 2 Composition and physicochemical properties of pyrimidine-based ionic liquids [A]X of Examples 5-8

[0084]

[0085] Examples 9-12

[0086] Examples 9-12 all provide a pyrimidine-based ionic liquid, and its structural formula is as follows:

[0087]

[0088] Examples 9 to 12 all provide a method for preparing a pyrimidine-based ionic liquid, including: adding the raw material hydrogenated phosphatidylcholine for forming the cation [A] and the raw material 2-methyl-1,4,5,6-tetrahydropyrimidinecarboxylic acid for forming the anion X successively into a small amount of water according to the molar ratios shown in Table 3, and stirring conventionally at 30 to 50 °C for 10 to 30 min until completely dispersed, and then adding water to make the total liquid volume 100%, thus obtaining the pyrimidine-based ionic liquid [A]X of Examples 9 to 12.

[0089] Among them, the molar ratios are rounded to integers according to the rounding rules.

[0090] Furthermore, the physical and chemical properties of the pyrimidine-based functionalized ionic liquids prepared in Examples 9 to 12 were detected, and the detection results are shown in Table 3. The results show that the pyrimidine-based ionic liquids [A]X obtained in Examples 9 to 12 have low viscosity, low surface tension, high ionic conductivity and high water content, as well as the characteristics of being neutral, polar and hydrophilic.

[0091] Furthermore, the pyrimidine-based ionic liquids [A]X obtained in Examples 9 to 12 are emulsions, and no layering phenomenon occurred after centrifuging at 4000 rpm for 15 minutes by the accelerated centrifugation method, and no flocculation phenomenon occurred after storing at room temperature for more than three months.

[0092] Table 3 Composition and physical and chemical properties of the pyrimidine-based ionic liquid [A]X of Examples 9 - 12

[0093]

[0094] Comparative Examples 1 - 8

[0095] Comparative Examples 1 to 8 respectively provide an ionic liquid, and their corresponding structural formulas are shown as follows:

[0096] Comparative Example 1: Comparative Example 2:

[0097] Comparative Example 3: Comparative Example 4:

[0098] Comparative Example 5: Comparative Example 6:

[0099] Comparative Example 7: Comparative Example 8:

[0100] Comparative Examples 1 to 8 all provide a method for preparing an ionic liquid, including: adding the raw material 2-amino-2-methyl-1-propanol that forms the cationic part of the ionic liquid and the corresponding raw material that forms the anionic part into a small amount of water in accordance with the molar ratios shown in Table 4, and stirring conventionally at 30-50 °C for 10-30 min until completely dissolved, and then adding water to make the total liquid volume 100%, thus obtaining the ionic liquids of Comparative Examples 1 to 8.

[0101] Among them, the molar ratios are rounded to integers.

[0102] The compositions and physicochemical properties of the ionic liquids of Comparative Examples 1 to 8 are shown in Table 4.

[0103] Experiments found that when the anionic part in the [A]X system is replaced with other similar compounds such as amino acids and their analogs, useful ionic liquids cannot be obtained in most cases.

[0104] Among them, when the anionic part X is replaced with basic amino acids, such as aspartic acid in acidic amino acids, arginine in basic amino acids, glycine in neutral non-polar aliphatic amino acids, methionine in polar neutral amino acids, and tryptophan in aromatic amino acids, ideal ionic liquids cannot be obtained.

[0105] Among them, when the anionic part X is replaced with non-protein amino acids, such as γ-aminobutyric acid, carnitine, and N,N,N-trimethylglycine, relatively stable ionic liquids can be obtained, but the solubility of such ionic liquids is far less than that of the examples.

[0106] Among them, for Comparative Examples 1 to 3, clear ionic liquids can be obtained by conventional stirring at 30-50 °C for 10-30 min. Among them, Comparative Example 1 has low viscosity and high ionic conductivity, and Comparative Examples 2 and 3 have high viscosity.

[0107] Among them, for Comparative Examples 4 to 8, even when the temperature, time, and stirring speed are increased to 80 °C, 120 minutes, and 2000 rpm, a clear solution can be obtained temporarily, but precipitation occurs rapidly when stirring stops.

[0108] Table 4 Compositions and Physicochemical Properties of Ionic Liquids of Comparative Examples 1-8

[0109]

[0110]

[0111] Application Examples 1 to 4

[0112] The preparation methods of the pyrimidine-based ionic liquids [A]X in Application Examples 1 to 4 are the same as those in Example 1. That is, according to the molar ratios (mol) and mole fractions (xi) in Table 5, the raw material 2-amino-2-methyl-1-propanol for forming the cation [A] and the raw material 2-methyl-1,4,5,6-tetrahydropyrimidinecarboxylic acid for forming the anion X are successively added to a small amount of water and stirred until dissolved to first obtain the hydrated ionic liquid solvent [A]X with the required concentration; then, the corresponding amount of API is added, and it is stirred conventionally at 30-50 °C for 10-30 min until completely dissolved, and water is added to make the total liquid volume 100%, thus obtaining the API preparations in Application Examples 1 to 4.

[0113] Among them, the molar ratio is rounded to an integer.

[0114] Dissolving typical poorly water-soluble APIs with the pyrimidine-based ionic liquids [A]X provided in Examples 1 to 4, the high-concentration API preparations in Application Examples 1 to 4 are obtained, proving that the pyrimidine-based ionic liquid solvent [A]X provided in the examples of the present invention can replace organic solvents.

[0115] Among them, antibacterial lipid refers to a lipid complex composed of lauric acid, palmitic acid, stearic acid, glyceryl caprylate, and glyceryl laurate in an equimolar ratio.

[0116] Among them, Application Example 4 forms a transparent micelle, suggesting that the critical micelle concentration (CMC) of the pyrimidine-based ionic liquid [A]X provided in Example 1 of the present invention may be around 1 M and plays a solubilization role.

[0117] Furthermore, stability tests were carried out on the API preparations obtained in Application Examples 1 to 4, and their compositions, properties, and stability test results are shown in Table 5. No layering occurred after centrifugation at 4000 rpm for 15 minutes using the accelerated centrifugation method. No flocculation occurred after storage at room temperature for more than three months, and the pH did not change.

[0118] Table 5 Compositions, properties, and stability test results of Application Examples 1 to 4

[0119]

[0120]

[0121] It should be noted that (1) the pyrimidine-based ionic liquids in the application examples of the present invention are ionic liquids prepared according to the ratios and raw materials of the examples. The ratios are the same, but the actual amounts used may be different. Therefore, the mole fraction xi of water is different from the aforementioned water content (i.e., the mole fraction of water) xi.

[0122] (2) Solvents are also added in the application examples, which also causes changes in the actual mole fractions of each component.

[0123] (3) Examples 1-12 and Application Examples 1-12, Comparative Examples 1-8 and Application Examples 13-16 do not correspond one by one. They are only prepared with reference to their raw materials and methods.

[0124] Application Examples 5-8

[0125] The preparation method of the pyrimidine-based ionic liquid [A]X in Application Examples 5-8 is the same as that in Example 5. That is, the raw material choline chloride for forming the cation [A] and the raw material 2-methyl-1,4,5,6-tetrahydropyrimidine carboxylic acid for forming the anion X are successively added to a small amount of water according to the composition molar ratio (mol) and mole fraction (xi) in Table 6 and stirred to dissolve. First, the hydrated ionic liquid solvent [A]X with the required concentration is prepared; then, the corresponding amount of API is added, and conventional stirring is carried out at 30-50 °C for 10-30 min until completely dissolved, and water is added to make the total liquid volume 100%, that is, the API solution of Application Examples 5-8 is obtained.

[0126] Among them, the molar ratio is rounded to an integer.

[0127] The pyrimidine-based ionic liquid [A]X prepared in Examples 5-8 is used to dissolve biomass materials such as lignin, vanillin, gallic acid and cytochrome C to obtain the solutions of Application Examples 5-8. The composition, properties and stability test results are shown in Table 6. The results show that the pyrimidine-based ionic liquid solvent [A]X obtained in Examples 5-8 can replace organic solvents to dissolve poorly soluble biomass materials.

[0128] Among them, Application Example 5 can dissolve at least 15% of lignin under conventional stirring at 30-50 °C. The obtained solution is brown and can be kept for at least 72 hours when standing at room temperature. Continuing to stand at room temperature for more than three months shows a slow precipitation process;

[0129] Among them, the vanillin, gallic acid and cytochrome C solutions obtained in Application Examples 6-8 do not precipitate or crystallize after being stored at room temperature for more than three months, and the pH value of the solution does not shift. Among them, the vanillin solution is a colorless transparent solution, the gallic acid solution is a yellowish transparent solution, and the cytochrome C solution is a dark red homogeneous liquid. The color and properties of the solution show no obvious changes after being stored at room temperature for more than three months.

[0130] Furthermore, the ultraviolet-visible spectrum of cytochrome C in Application Example 8 was measured ( Figure 2 ). From Figure 2 it can be seen that compared with the dry cytochrome C standard stored at -20 °C, the cytochrome C solution obtained in Application Example 8 has more characteristic oxidation state and reduction state absorption peaks at 408 nm and 520 nm after being stored at room temperature for three months ( Figure 2In A and B). It is prompted that the pyrimidine-based ionic liquid [A]X provided by the embodiments of the present invention has the function of dissolving and stabilizing the spatial conformation of proteins, which is beneficial to maintaining the oxidation and reduction activities of cytochrome C for a long time.

[0131] Table 6 Composition, properties, and stability test results of Application Examples 5-8

[0132]

[0133] Application Examples 9-12:

[0134] The preparation method of the pyrimidine-based ionic liquid [A]X in Application Examples 9-12 is the same as that in Example 9. That is, the raw material of hydrogenated phosphatidylcholine for forming the cation [A] and the raw material of 2-methyl-1,4,5,6-tetrahydropyrimidinecarboxylic acid for forming the anion X are successively added to a small amount of water and stirred to dissolve according to the composition molar ratio (mol) and mole fraction (xi) in Table 7, and the hydrated ionic liquid solvent [A]X with the required concentration is first prepared; then, the corresponding amount of API component is added, and it is stirred conventionally at 30-50 °C for 10-30 min until it is completely dissolved, and water is added to make the total liquid volume 100%, and the API emulsions of Application Examples 9-12 are obtained.

[0135] Among them, the molar ratio is rounded to an integer.

[0136] Dissolving the typical low-water-soluble API with the pyrimidine-based ionic liquid [A]X provided in Examples 9-12, the API emulsions of Application Examples 9-12 are obtained, which proves that the pyrimidine-based ionic liquid solvent [A]X provided by the embodiments of the present invention can replace organic solvents and surfactants, has strong solubility for typical low-water-soluble APIs, and stable API emulsions can be obtained without co-surfactants.

[0137] Furthermore, accelerated stability tests were carried out on the API preparations obtained in Application Examples 9-12, and the test results are shown in Table 7. The accelerated centrifugation method was used to centrifuge at 4000 rpm for 15 minutes, and the results showed no delamination or flocculation phenomenon, and no delamination or flocculation occurred after standing at room temperature for more than three months, and the pH did not change.

[0138] Table 7 Composition, properties, and stability test results of Application Examples 9-12

[0139]

[0140]

[0141] Application Examples 13-16:

[0142] The preparation methods of the ionic liquids (ILs) in Application Examples 13 to 16 were the same as those in Comparative Example 1. That is, according to the molar ratios (mol) and mole fractions (xi) in Table 8, the raw material 2-amino-2-methyl-1-propanol for forming the cationic part [A] of the ionic liquid (IL) and the raw material γ-aminobutyric acid for forming the anionic part were successively added to a small amount of water and stirred until dissolved. First, the IL with the required concentration was prepared; then, the corresponding amount of API was added, and the mixture was continuously stirred at a speed of 1000 - 2000 rpm for 30 - 120 min at 30 - 80 °C until completely dissolved, and water was added to make the total liquid volume 100%, thus obtaining the API preparations in Application Examples 13 to 13;

[0143] Among them, the molar ratio was rounded to an integer according to the rounding rule of "rounding up if the digit to the right of the rounding digit is 5 or more, and rounding down if it is less than 5".

[0144] The experimental results showed that the solubility of the ionic liquid (IL) obtained in Comparative Example 1 was much lower than that of the pyrimidine-based ionic liquid [A]X obtained in the examples, but it could still replace traditional organic solvents to prepare low-concentration API preparations; as the API concentration increased, the solution stability decreased rapidly. For example, 10% salicylic acid and 10% azelaic acid solutions quickly formed dendritic crystals and could not be restored when left standing at room temperature.

[0145] Furthermore, the API preparations obtained in Application Examples 13 to 16 were subjected to stability tests, and their compositions, properties, and stability test results are shown in Table 8.

[0146] Table 8 Compositions, properties, and stability test results of Application Examples 13 to 16

[0147]

[0148] Molecular simulation experiment

[0149] Based on the rapid development of theory and computational chemistry, current chemistry is transitioning from a pure experimental science to a science that synergistically promotes "experiment, calculation, and theory". Computational simulation can, to a certain extent, predict and explain experimental results (China National Natural Science Foundation Committee, Chinese Academy of Sciences, "China's Disciplinary Development Strategy: Theoretical and Computational Chemistry", Science Press, First Edition, 2016).

[0150] According to the second law of thermodynamics, the direction and limit of a process can be judged. That is, taking the change in Gibbs free energy (ΔG) as the thermodynamic criterion, the direction and limit of a change can be predicted under specific conditions. Under the conditions of constant temperature, constant pressure, and no non-volume work, the process in a closed system always spontaneously proceeds in the direction of decreasing Gibbs free energy until it reaches the equilibrium state with the minimum Gibbs free energy under these conditions. For a spontaneous reaction (ΔG < 0) at constant temperature and pressure, it is entirely possible to proceed automatically at the specified temperature and pressure (compiled by Li Xianguo, "Physical Chemistry", Peking University Press, First Edition, 2016).

[0151] The molecular simulation experimental data of Examples 1 to 35 are summarized in Table 9. The pyrimidine ionic liquids used in Examples 13 to 35 were prepared by referring to the preparation method provided in Example 1, with the only difference being that the corresponding raw materials were changed.

[0152] Among them, Cv represents the heat capacity of the reaction, in cal / mol-kelvin; ΔG represents the Gibbs free energy change of the reaction, in au; α represents the polarizability, in au; μ represents the dipole moment, in Debye; BE represents the hydrogen bond energy, in kcal / mol; d represents the bond length, in θ represents the bond angle, unit (°);

[0153] The intermolecular hydrogen bond structure and geometric parameters are shown in the figure below. X represents the hydrogen bond donor, A (A1, A2) represents the hydrogen bond acceptor, d (d1, d2) represents the bond length, and θ (θ1, θ2) represents the bond angle.

[0154]

[0155] The results of molecular simulation experiments show that the Gibbs free energy change (ΔG < 0) of Examples 1 to 35 at 298.15K and 1.00Atm predicts that the reactions can proceed spontaneously. Strong hydrogen bonds, double hydrogen bonds or triple hydrogen bonds are formed between molecules, thus giving the [A]X system strong solubility and stability.

[0156] Among them, when R2 in the X structure is replaced by hydroxyl, the molar heat capacity and hydrogen bond energy of the [A]X system are higher, indicating that the thermodynamic stability and solubility are further increased; when [A] is choline chloride, hydrogenated phosphatidylcholine, choline, phosphatidylcholine, phosphatidylethanolamine and N,N,N-trimethylglycine, relatively weak hydrogen bonds are formed between molecules, but due to the support of double or triple hydrogen bonds, there is still a high bond energy and higher heat capacity. Therefore, it is predicted that thermodynamically stable products [A]X can be formed.

[0157] Table 9 Molecular simulation experimental data of Examples 1 to 35

[0158]

[0159]

[0160]

[0161]

[0162] Furthermore, the results of molecular simulation experiments show that when the anion part X in the pyrimidine-based ionic liquid [A]X system is replaced by 20 basic amino acids or non-protein amino acids (i.e., Comparative Examples 1-23 in Table 10), completely different results are obtained. The molecular simulation experimental data are summarized in Table 10.

[0163] Among them, in Comparative Examples 1-3, when the anion part X is replaced by non-protein amino acids, such as γ-aminobutyric acid, carnitine or N,N,N-trimethylglycine, the change in Gibbs free energy (ΔG≤0) for the reaction with the cation part [A] such as 2-amino-2-methyl-1-propanol predicts a tendency to form an ionic liquid.

[0164] Among them, in Comparative Examples 4-23, when the anion part X is replaced by 20 basic amino acids, the change in Gibbs free energy (ΔG≥0) for the reaction with the cation part 2-amino-2-methyl-1-propanol predicts that the reaction cannot occur spontaneously under normal temperature and pressure.

[0165] The results of the molecular simulation experiments are consistent with the experimental results of Comparative Examples 1-8 (Table 4).

[0166] Table 10 Molecular simulation experimental data of Comparative Examples 1-23

[0167]

[0168] Abbreviations: Gab (γ-aminobutyric acid), Car (carnitine), Bet (N,N,N-trimethylglycine), Glu (glutamic acid), Asp (aspartic acid), Arg (arginine), Lys (lysine), His (histidine), Gly (glycine), Ala (alanine), Ser (serine), Cys (cysteine), Cys- (cystine), Thr (threonine), Met (methionine), Glu- (glutamine), Val (valine), Leu (leucine), Ile (isoleucine), Phe (phenylalanine), Tyr (tyrosine), Pro (proline), Try (tryptophan).

[0169] Furthermore, the reaction paths of the pyrimidine-based ionic liquid [A]X in Example 1 and the ionic liquid (IL) in Comparative Example 1 were compared through molecular simulation experiments ( Figure 3 ). The results show that the reaction energy barrier in Example 1 is much lower than that in Comparative Example 1 ( Figure 3 A and B therein).

[0170] Among them, the change in Gibbs free energy (ΔG<0) of the reaction in Example 1 predicts that the reaction can occur spontaneously under the conditions of 298.15K and 1.00 Atm. The results of the molecular simulation experiments are consistent with the experimental results of Examples 1-4.

[0171] Among them, the Gibbs free energy change of the reaction in Comparative Example 1 (ΔG≤0) and the reaction energy barrier are significantly higher than those in Example 1, predicting that it is difficult to form a stable ionic liquid under normal temperature and pressure. The results of the molecular simulation experiment are consistent with the experimental results of Comparative Examples 1-8.

[0172] Furthermore, the solvent effect was calculated in the molecular simulation experiment. The solvent effect is to simulate the solvent effect of the ionic liquid [A]X in an aqueous solution, that is, to further verify the solubility of the pyrimidine-functionalized hydrated ionic liquid solvent [A]X provided in Example 1 of the present invention for typical low-water-soluble APIs through the molecular simulation experiment.

[0173] The solvent effect data are summarized in Table 11.

[0174] Among them, ΔEE represents the change in solvation free energy, with the unit of a.u.; ΔH represents the enthalpy change of the solvation effect, with the unit of a.u.

[0175] The molecular simulation experiment data show that compared with the pure ionic liquid [A]X, the solvent effect of the hydrated ionic liquid [A]X significantly increases the polarizability and dipole moment. Therefore, it has higher polarity and hydrophilic structure, making more water molecules in the bound water state, creating a favorable hydrophobic microenvironment for the protein domain to maintain the thermodynamic stability of the spatial conformation, thereby avoiding protein unfolding. The molecular simulation experiment data support the experimental conclusion of Application Example 8, showing the application value of the pyrimidine ionic liquid [A]X provided in Example 1 of the present invention in the biomedical industry.

[0176] Furthermore, the thermodynamic energies of different spatial conformations of cytochrome C in different physical states were compared through molecular simulation experiments ( Figure 4 ). Including the thermodynamic energies of various conformations in the gaseous state and aqueous solutions (I, III), pure ionic liquid [A]X and hydrated ionic liquid [A]X (II, V), and the aqueous solution of classical protein stabilizer ammonium sulfate (IV). The results show that the thermodynamic energy of cytochrome C in the hydrated ionic liquid [A]X is the lowest, indicating that its spatial conformation is more stable ( Figure 4 in V). The simulation experiment data support the conformational characterization results of the ultraviolet-visible spectrum of cytochrome C in Application Example 8 ( Figure 2 ).

[0177] Table 11 Solvent effect experimental data

[0178]

[0179] It should be understood that the above-mentioned molecular simulation experiment data only represent the theoretical value in a specific system, and the data obtained in different systems or models may be different;

[0180] It should be understood that the API preparations prepared in the above application examples are only for testing the application value of the pyrimidine-based ionic liquids provided in the embodiments of the present invention, and should not be understood as specific or particular preparations that can be directly applied.

[0181] The above are only the preferred embodiments of the present invention and are not used to limit the present invention. For those skilled in the art, the present invention can have various changes and modifications. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A pyrimidine-based ionic liquid, characterized in that, The pyrimidine-based ionic liquid is a pyrimidine-based functionalized hydrated ionic liquid solvent; the name of the pyrimidine-based ionic liquid is [A]X, where [A] represents the cationic part and X represents the anionic part; the structural formula of the pyrimidine-based ionic liquid is shown as follows: Wherein, R1 represents a C1-C4 alkyl group, and R2 represents hydrogen; [A] is any one selected from the nitrogen-containing groups represented by the following structural formulas: , , , , and .

2. The pyrimidine-based ionic liquid according to claim 1, wherein [A] is any one of the groups represented by the following structural formulas: and 。 3. The pyrimidine-based ionic liquid according to claim 1, wherein R1 represents a C1-C3 alkyl group.

4. The pyrimidine-based ionic liquid according to claim 3, characterized in that, R1 is methyl or ethyl.

5. The pyrimidine-based ionic liquid according to claim 1, wherein The molar ratio of [A] to X is (1:1)-(4:1).

6. The pyrimidine-based ionic liquid according to any one of claims 1-5, characterized in that, The molar ratio of [A] to X is (2:1)-(3:1).

7. A method for preparing the pyrimidine-based ionic liquid according to claim 1, characterized in that, It includes: Mix and dissolve the raw materials for forming the cation [A] and the raw materials for forming the anion X.

8. The preparation method according to claim 7, characterized in that, The preparation is carried out under non-vacuum conditions.

9. The preparation method according to claim 7, characterized in that, The temperature for mixing and dissolving is 30-50 °C, and the time is 10-30 min.

10. The preparation method according to claim 7, characterized in that, Use water to dissolve the raw materials for forming the cation [A] and the raw materials for forming the anion X.

11. Use of the pyrimidine-based ionic liquid according to claim 1 as a solvent for dissolving low-water-soluble APIs and biomass.

12. The application according to claim 11, wherein, The low-water-soluble API is an API with a solubility less than 3 g at 20 °C.

13. The application according to claim 12, wherein The low-water-soluble API is selected from any one of ibuprofen, salicylic acid, azelaic acid, antibacterial fat, retinol, retinoic acid, and lignin, vanillin, gallic acid, and cytochrome C.

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