Preparation method of sulfolane methacrylate

Abstract

The invention relates to the technical field of organic synthesis, in particular to a preparation method of sulfolane methacrylate. The preparation method comprises the following steps: carrying out esterification reaction on 3-hydroxy sulfolane and methacryloyl chloride in a first solvent in a protective gas atmosphere in the presence of organic alkali; the first solvent is a low-boiling-point organic solvent; after the esterification reaction is finished, carrying out quenching treatment on the reaction liquid, and carrying out liquid separation to obtain an organic layer liquid; performing chromatography treatment on the organic layer liquid by adopting a silica gel column to obtain oily liquid; the oily liquid is subjected to crystallization treatment, and solid sulfolane methacrylate is obtained; the crystallization treatment temperature is-30 DEG C to-10 DEG C, and an adopted crystallization solvent is a mixed solvent of alkane and alcohol. The preparation method disclosed by the invention is simple to operate, few in byproducts, high in yield and high in preparation efficiency, and the sulfolane methacrylate solid with high purity and good stability can be obtained.

Description

Technical Field

[0001] The present application relates to the technical field of organic synthesis, and in particular to a method for preparing sulfolane methacrylate. Background Art

[0002] α-Cyanoacrylate medical adhesives are based on α-cyanoacrylate monomers as their primary active ingredient. Upon contact with moisture (such as blood and tissue fluid), they rapidly polymerize and cure to form a strong film. They offer advantages such as fast curing, high bond strength, and excellent biocompatibility, making them widely used in surgical procedures, wound closure, and hemostasis. α-Cyanoacrylate monomers generate heat during polymerization (polymerization heat). The addition of sulfolane methacrylate monomers can reduce this heat and prevent thermal damage to tissues.

[0003] Sulfolane methacrylate is a methacrylate compound containing a sulfolane group. Currently, the main method for preparing sulfolane methacrylate is as follows: 3-sulfolane is reacted under alkaline conditions to form 3-hydroxysulfolane, which is then esterified with methacryloyl chloride to form sulfolane methacrylate. Because this method uses highly reactive methacryloyl chloride, the reaction solution contains a large amount of impurities after the esterification reaction, making it difficult to obtain high-purity sulfolane methacrylate using conventional purification methods. However, sulfolane methacrylate used in the preparation of α-cyanoacrylate medical adhesives requires a high purity. Therefore, how to isolate and obtain high-purity sulfolane methacrylate from the reaction solution is a currently unresolved technical problem.

[0004] In Langmuir 2016, 32, 3, 765–771, the crude product is purified by column chromatography (acetone / n-hexane = 1:3) to obtain a colorless oil. However, this method has low purification efficiency, making it difficult to scale up. It also requires high-temperature, reduced-pressure concentration to remove the acetone and n-hexane used in the column chromatography process, which can trigger polymerization and deteriorate the sample. Furthermore, the sample is a colorless to pale yellow oil with poor stability and prone to polymerization. In CN116768850A, the crude product is dissolved in a 10–30% acetonitrile aqueous solution and purified using preparative high-performance liquid chromatography, with the main peak solution collected in fractions. The main peak solution is concentrated under reduced pressure at 30 ± 5°C, and the concentrated sample solution is transferred to a freeze dryer. The freeze drying process includes pre-freezing, main drying, and desorption drying. The flocculent product obtained after freeze drying is sulfolane methacrylate. The above method reduces losses by using preparative chromatography and improves stability through freeze drying. However, the high cost and complex operation of preparative chromatography and freeze drying equipment are not conducive to large-scale production.

[0005] Based on this, it is necessary to develop a preparation method of sulfolane methacrylate with high stability, high purity and suitable for industrial production. Summary of the Invention

[0006] Based on this, one or more embodiments of the present application provide a method for preparing cyclopentane methacrylate, which has simple operation, few by-products, high yield, high preparation efficiency, and can obtain solid high-purity cyclopentane methacrylate, thereby improving the stability of the cyclopentane methacrylate product.

[0007] The technical solution of this application includes the following contents: A method for preparing sulfolane methacrylate comprises the following steps: Under the conditions of a protective gas atmosphere and the presence of an organic base, 3-hydroxysulfolane and methacryloyl chloride are subjected to an esterification reaction in a first solvent, wherein the first solvent is a low-boiling-point organic solvent; After the esterification reaction is completed, the reaction solution is quenched and separated to obtain an organic layer liquid; The organic layer liquid is subjected to chromatography using a silica gel column to obtain an oily liquid; Crystallizing the oily liquid to obtain solid sulfolane methacrylate; The temperature of the crystallization treatment is -30°C to -10°C, and the crystallization solvent used is a mixed solvent of alkane and alcohol.

[0008] In some embodiments, the preparation method satisfies at least one of the following conditions (1) to (3): (1) The molar ratio of the 3-hydroxysulfolane to the methacryloyl chloride is 1:(1-2); (2) the molar ratio of the 3-hydroxysulfolane to the organic base is 1:(1-3); (3) The mass volume ratio (g / mL) of the 3-hydroxycyclopentane sulfone and the first solvent is 1:3-10.

[0009] In some embodiments, the esterification reaction temperature is 0° C. to 40° C., and the reaction time is 1 to 6 hours.

[0010] In some embodiments, the preparation method satisfies at least one of the following conditions (1) to (2): (1) The organic base includes at least one of triethylamine, diisopropylethylamine, pyridine, 4-dimethylaminopyridine, 1,8-diazabicycloundec-7-ene, sodium methoxide, potassium tert-butoxide and lithium diisopropylamide; (2) The first solvent includes at least one of dichloromethane, tetrahydrofuran and acetone.

[0011] In some embodiments, before the organic layer liquid is subjected to chromatography using a silica gel column, the organic layer liquid is washed with ethanol and saturated saline, and then dried.

[0012] In some embodiments, the step of subjecting the organic layer liquid to chromatography using a silica gel column to obtain an oily liquid comprises: Concentrating the organic layer liquid to obtain a concentrate; Adsorbing the concentrate with silica gel powder to obtain a silica gel sample; The silica gel sample is loaded onto a silica gel column, and gradient eluted with a mixed solvent of petroleum ether and ethyl acetate to obtain an eluate; The eluate is concentrated to obtain the oily liquid.

[0013] Furthermore, the step of adsorbing the concentrate with silica gel powder to obtain a silica gel sample comprises: dissolving the concentrate in a second solvent, adding silica gel powder and mixing to obtain a mixture; volatilizing the solvent in the mixture to obtain the silica gel sample; The second solvent is an ether organic solvent.

[0014] Furthermore, the second solvent includes at least one of diethyl ether, isopropyl ether, methyl tert-butyl ether, tetrahydrofuran, dioxane and ethylene glycol monomethyl ether.

[0015] In some embodiments, in the crystallization solvent, the alkane comprises at least one of petroleum ether, n-hexane, n-heptane, n-pentane, cyclohexane, methylcyclohexane and n-octane; and / or, The alcohol includes at least one of methanol, ethanol, isopropanol, n-butanol, ethylene glycol and glycerol.

[0016] Furthermore, in the crystallization solvent, the volume ratio of the alkane to the alcohol is (1.5-2.5):1.

[0017] The advantages of the technical solution of this application include at least the following: The preparation method of the present application involves conducting an esterification reaction between 3-hydroxysulfolane and methacryloyl chloride in a first solvent (a low-boiling-point organic solvent) under a protective gas atmosphere and in the presence of an organic base. The reaction yield is high and the amount of by-products is low, providing a good material basis for simplifying the post-processing steps. After the esterification reaction is completed, the reaction solution can be naturally separated after quenching, without the need for extraction or other operations, thereby simplifying the operation steps. At the same time, the main solvent in the obtained organic layer liquid is a low-boiling-point organic solvent, which can be quickly evaporated at low temperature, thereby simplifying the operation steps and avoiding the introduction of by-products in the concentration step. After the organic layer liquid is chromatographed on a silica gel column, most impurities can be removed, without the need for preparative chromatography, thereby simplifying the operation steps. The oily liquid obtained after the chromatography treatment is crystallized at -30°C to -10°C to obtain solid methacrylate sulfolane ester, which has the advantages of high purification efficiency, high product stability, and high purity.

[0018] The sulfolane methacrylate prepared by the preparation method of the present application has high purity and good stability, thereby ensuring the quality of the α-cyanoacrylate medical adhesive product, being able to better meet the intended use of the product without affecting the biocompatibility and clinical safety of the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] In order to more clearly illustrate the specific implementation methods of the present application or the technical solutions in the prior art, the following is a brief introduction to the drawings required for use in the specific implementation methods or the description of the prior art. Obviously, the drawings described below are some implementation methods of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without any creative work.

[0020] Figure 1 Schematic diagram of the synthesis route of sulfolane methacrylate according to one embodiment of the present application.

[0021] Figure 2 This is a hydrogen NMR spectrum of 3-hydroxysulfolane, a raw material in one embodiment of the present application.

[0022] Figure 3 This is a gas chromatogram of the light yellow oily liquid (3-methylacrylate cyclopentane sulfonate product) of Example 1 of the present application.

[0023] Figure 4 This is a gas chromatogram of the white powder solid (3-methylacrylate cyclopentane sulfonate product) of Example 1 of the present application.

[0024] Figure 5 This is the H NMR spectrum of the white powder solid (3-methylacrylate cyclopentane sulfonate product) of Example 1 of the present application. DETAILED DESCRIPTION

[0025] Below in conjunction with embodiment and example, further elaborate the application.It should be understood that these examples are only used to illustrate the application and are not used to limit the scope of the application.In addition, it should be understood that after reading the content taught in this application, those skilled in the art can make various changes or modifications to the application, and these equivalent forms also fall within the protection scope of the claims appended hereto.

[0026] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as those commonly understood by those skilled in the art to which this application pertains. The terms used herein in the specification of this application are for the purpose of describing specific embodiments only and are not intended to limit this application.

[0027] the term Unless otherwise specified or incompatible herewith, the terms and phrases used herein shall have the following meanings: The term "and / or" as used herein includes any one of two or more related listed items, and also includes any and all combinations of the related listed items, wherein the any and all combinations include any two related listed items, any more related listed items, or a combination of all related listed items. It should be noted that when at least three items are connected by at least two conjunctions selected from "and / or", "or / and", and "and / or", it should be understood that in this application, the technical solution undoubtedly includes technical solutions connected by "logical and" and technical solutions connected by "logical or". For example, "A and / or B" includes three parallel solutions: A, B, and A+B.

[0028] In this application, "further" and the like are used for descriptive purposes to indicate differences in content, but should not be understood as limiting the scope of protection of this application.

[0029] In this application, the terms "first," "second," "third," and "fourth," etc., are used for descriptive purposes only and should not be construed as indicating or implying relative importance or quantity, nor as implicitly indicating the importance or quantity of the technical features indicated. Furthermore, the terms "first," "second," "third," and "fourth," etc., are used only for non-exhaustive enumeration and description purposes and should not constitute closed-ended limitations on quantity.

[0030] In this application, the technical features described in an open manner include closed technical solutions composed of the listed features, and also include open technical solutions containing the listed features.

[0031] In this application, when referring to a numerical interval (i.e., a numerical range), unless otherwise specified, the optional numerical distribution within the numerical interval is considered continuous and includes the two numerical endpoints of the numerical range (i.e., the minimum and maximum values), as well as every numerical value between these two numerical endpoints. Unless otherwise specified, when a numerical interval refers only to integers within the numerical interval, it includes the two numerical endpoints of the numerical range, as well as every integer between the two endpoints. In addition, when multiple ranges are provided to describe a feature or characteristic, these ranges can be combined. In other words, unless otherwise specified, ranges disclosed herein should be understood to include any and all subranges subsumed therein.

[0032] In this application, weight and mass have the same meaning and can be mass units well known in the chemical industry such as μg, mg, g, kg, etc.

[0033] In this application, the mass-to-volume ratio refers to the ratio of the mass of substance A to the volume of substance B at room temperature, expressed in g / mL; for example, the mass-to-volume ratio (g / mL) of 3-hydroxysulfolane and the first solvent is 1:3~10, which means that the ratio of the mass of 3-hydroxysulfolane to the volume of the first solvent is 1:3~10 (g / mL).

[0034] The technical solution of the embodiment of the present application provides a method for preparing sulfolane methacrylate, comprising the following steps: Under the conditions of a protective gas atmosphere and the presence of an organic base, 3-hydroxysulfolane and methacryloyl chloride are subjected to an esterification reaction in a first solvent, wherein the first solvent is a low-boiling-point organic solvent; After the esterification reaction is completed, the reaction solution is quenched and separated to obtain an organic layer liquid; The organic layer liquid is subjected to chromatography on a silica gel column to obtain an oily liquid; The oily liquid is crystallized to obtain sulfolane methacrylate; The temperature of the crystallization treatment is -30°C to -10°C, and the crystallization solvent used is a mixed solvent of alkane and alcohol.

[0035] In the technical solutions of the embodiments of the present application, the raw material 3-hydroxysulfolane can be purchased or prepared. The preparation method of 3-hydroxysulfolane can refer to published literature.

[0036] For example, a method for preparing 3-hydroxysulfolane includes the following steps: subjecting 3-sulfolane to an aqueous base solution through an addition reaction to obtain 3-hydroxysulfolane. Optionally, the molar ratio of 3-sulfolane to the base can be 1:(1-4). Optionally, the base in the aqueous base solution comprises at least one of sodium hydroxide, potassium hydroxide, potassium carbonate, and sodium carbonate. Optionally, the addition reaction temperature can be 0°C to 60°C, and the reaction time can be 2-24 hours.

[0037] In some embodiments, the preparation method satisfies at least one of the following conditions (1) to (3): (1) The molar ratio of 3-hydroxysulfolane to methacryloyl chloride is 1:(1-2), for example 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, etc.; (2) The molar ratio of 3-hydroxysulfolane to the organic base is 1:(1-3), for example, 1:1, 1:1.2, 1:1.5, 1:1.8, 1:2, 1:2.2, 1:2.5, 1:2.8, 1:3, etc.; (3) The mass volume ratio (g / mL) of 3-hydroxycyclopentane sulfone to the first solvent is 1:3 to 10, for example, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8, 1:9, 1:10, etc.

[0038] Furthermore, the molar ratio of 3-hydroxysulfolane to methacryloyl chloride is 1:(1.1-1.5).

[0039] Furthermore, the molar ratio of 3-hydroxysulfolane to the organic base is 1:(1.5-2).

[0040] Furthermore, the mass volume (g / mL) ratio of 3-hydroxysulfolane to the first solvent is 1:6-10.

[0041] In some embodiments, the temperature of the esterification reaction is 0°C~40°C, for example, 0°C, 5°C, 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, etc., and the time of the esterification reaction is 1~6h, for example, 1h, 2h, 3h, 4h, 5h, 6h, etc.

[0042] Furthermore, the esterification reaction temperature is 20° C. to 40° C., and the reaction time is 1 to 3 hours.

[0043] In some embodiments, the preparation method satisfies at least one of the following conditions (1) to (2): (1) The organic base includes at least one of triethylamine, diisopropylethylamine, pyridine, 4-dimethylaminopyridine, 1,8-diazabicycloundec-7-ene, sodium methoxide, potassium tert-butoxide and lithium diisopropylamide; (2) The first solvent includes at least one of dichloromethane, tetrahydrofuran and acetone.

[0044] Furthermore, the organic base is triethylamine, diisopropylethylamine or 4-dimethylaminopyridine.

[0045] Furthermore, the first solvent is dichloromethane or tetrahydrofuran.

[0046] In some embodiments, before the organic layer liquid is subjected to chromatography using a silica gel column, the organic layer liquid is washed with ethanol and saturated saline, and then dried.

[0047] In some embodiments, the step of subjecting the organic layer liquid to chromatography using a silica gel column to obtain an oily liquid comprises: Concentrating the organic layer liquid to obtain a concentrate; The concentrate was subjected to adsorption treatment with silica gel powder to obtain a silica gel sample; The silica gel sample was loaded onto a silica gel column and gradient eluted with a mixed solvent of petroleum ether and ethyl acetate to obtain an eluate; The eluate was concentrated to obtain an oily liquid.

[0048] Furthermore, the step of adsorbing the concentrate with silica gel powder to obtain a silica gel sample includes: dissolving the concentrate in a second solvent, adding silica gel powder and mixing to obtain a mixture; The solvent in the mixture was evaporated to obtain a silica gel sample; The second solvent is an ether organic solvent.

[0049] Furthermore, the second solvent includes at least one of diethyl ether, isopropyl ether, methyl tert-butyl ether, tetrahydrofuran, dioxane and ethylene glycol monomethyl ether.

[0050] Furthermore, the second solvent is diethyl ether, methyl tert-butyl ether or tetrahydrofuran.

[0051] In some embodiments, the temperature of the crystallization treatment is -30°C to -10°C, for example -30°C, -25°C, -20°C, -15°C, -10°C, etc.

[0052] In some embodiments, in the crystallization solvent, the alkane comprises at least one of petroleum ether, n-hexane, n-heptane, n-pentane, cyclohexane, methylcyclohexane and n-octane; and / or, The alcohol includes at least one of methanol, ethanol, isopropanol, n-butanol, ethylene glycol and glycerol.

[0053] Furthermore, in the crystallization solvent, the volume ratio of alkane to alcohol is (1.5~2.5):1, for example, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1, 2:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, etc.

[0054] In some embodiments, the crystallization solvent is a mixed solvent of petroleum ether and methanol, a mixed solvent of n-heptane and methanol, a mixed solvent of petroleum ether and ethanol, or a mixed solvent of n-heptane and ethanol.

[0055] The following are some specific examples.

[0056] For experimental parameters not specified in the following specific examples, reference is made to the guidance given in this application document, and reference may also be made to experimental manuals in the art or other experimental methods known in the art, or to the experimental conditions recommended by the manufacturer.

[0057] The raw materials and reagents involved in the following specific examples can be obtained commercially, or can be prepared by those skilled in the art according to known methods.

[0058] The following examples describe a self-prepared 3-hydroxysulfolane product: 20 g of 3-sulfolane was dissolved in 42 mL of a 2N aqueous sodium hydroxide solution. The mixture was stirred at room temperature for 24 hours, and then approximately 7 mL of 12N hydrochloric acid was slowly added to adjust the pH of the reaction solution to 6.5-7.0. The resulting mixture was dehydrated under reduced pressure at 70-90°C, and 30 mL of acetone was added to the concentrate. The salt was filtered and the solvent was removed from the filtrate under reduced pressure at 40°C. The resulting crude 3-hydroxysulfolane product was maintained at 160°C for 2 hours and then subjected to reduced pressure distillation at 200°C to obtain 17.6 g of the product 3-hydroxysulfolane. H-NMR spectrum data: 1 HNMR (400MHz,CDCl3) δ 4.74-4.70(m,1H), 3.83(s,1H), 3.39-3.25(m,2H), 3.18-3.10(m,2H), 2.40-2.32(m,2H), see Figure 2 . Example

[0059] This embodiment provides a method for preparing 3-methacrylate sulfolane ester of the present application, comprising the following steps: (1) Dissolve 10.0 g of 3-hydroxycyclobutane sulfone in a mixture of 60 mL of anhydrous dichloromethane (first solvent) and 9.87 g of 4-dimethylaminopyridine (organic base). Cool the reaction solution to 0°C and protect with nitrogen. Add 9.21 g of methacryloyl chloride to the reaction solution at a uniform rate over 60 minutes. Maintain the temperature of the reaction solution at 0°C ± 0.5°C during the addition. After the addition is complete, react the reaction solution at 0°C for 30 minutes, then raise it to room temperature (15°C ~ 25°C) and react for 120 minutes. Sampling is performed to check if the raw materials have reacted completely. The product accounts for 86.47% of the reaction solution, and the by-product accounts for 4.24%.

[0060] The reaction solution was quenched with 30 mL of saturated sodium bicarbonate aqueous solution, and the liquid was separated to obtain an organic layer liquid. The organic layer liquid was washed with ethanol, then washed with saturated brine, then dried over anhydrous sodium sulfate, and then concentrated under reduced pressure to obtain a concentrate. The concentrate was dissolved in dichloromethane, adsorbed with silicon powder, and the solvent was evaporated to obtain a silica gel sample. The silica gel sample was loaded onto a silica gel column for chromatography. The eluent used for chromatography was a mixture of petroleum ether and ethyl acetate. The elution gradient was petroleum ether: ethyl acetate = 20:1 (v / v) 1575 mL, petroleum ether: ethyl acetate = 2:1 (v / v) 1500 mL. The eluents with a gradient of petroleum ether: ethyl acetate = 2:1 (v / v) were collected and combined, and concentrated under reduced pressure to obtain 8.7 g of a light yellow oily liquid with a purity of 94.45%. The by-product accounted for 3.7%. The gas chromatogram of the light yellow oily liquid is shown in FIG. Figure 3 .

[0061] (2) 6 g of the light yellow oily liquid was recrystallized at -20 °C using petroleum ether (24 mL) and ethanol (12 mL) as crystallization solvents. The resulting solid was dried at 0 °C to constant weight to obtain 4.8 g of a white powder solid with a purity of 99.85%. The by-product polymethacrylic acid chloride was effectively removed. The gas chromatogram of the white powder solid is shown in Figure 4 H NMR data: 1H NMR (400MHz, CDCl3) δ 6.16 (d, J=1.2Hz, 1H), 5.67 (d, J=1.6Hz, 1H), 5.58–5.55 (m,1H),3.46-3.41 (m,1H), 3.27–3.18 (m,3H), 2.55–2.48 (m,2H), 1.95 (s,3H), see the spectrum. Figure 5 , confirmed to be 3-methylacrylate cyclopentane sulfonate. Example

[0062] 3-Methacrylate cyclopentanesulfonate was prepared using a method substantially identical to that of Example 1, except that the organic base in step (1) was 14.9 g of anhydrous triethylamine. 7.9 g of a pale yellow oily liquid was obtained. 4.5 g of a white powdery solid was obtained with a purity of 99.31%. Example

[0063] 3-Methacrylate cyclopentane sulfonate was prepared using a method substantially identical to that of Example 1, except that the crystallization solvent in step (2) was a mixed solvent of cyclohexane (24 mL) and methanol (12 mL), and the crystallization temperature was −20° C. A white powder (4.7 g) was obtained with a purity of 99.52%. Example

[0064] 3-Methacrylate cyclobutyl sulfone ester was prepared by a method substantially the same as that in Example 1, except that tetrahydrofuran was used as the first solvent in step (1). The product accounted for 88.16% of the reaction solution, but the by-product accounted for 9.28%, which was much greater than 4.24%. As a result, the product could not be removed by column, and further resulted in a small amount of by-products being present in the product after subsequent crystallization. Thus, 5.6 g of the product 3-methacrylate cyclobutyl sulfone ester was obtained as a white powder solid. Although it was greater than 4.8 g, the purity was reduced to 95.78%. The peak of polymethacrylic acid chloride was visible in the product chromatogram. Example

[0065] 3-Methacrylate cyclopentane sulfonate was prepared by a method substantially the same as that in Example 1, except that the reaction temperature was increased to 35°C in step (1). The product accounted for 87.14% of the reaction solution, but the by-product accounted for 7.93%, which was much greater than 4.24%. As a result, the by-product could not be removed by column, and further resulted in the presence of a small amount of by-product in the product after subsequent crystallization. Thus, 6.1 g of the product 3-methacrylate cyclopentane sulfonate was obtained as a white powder solid. Although it was greater than 4.8 g, the purity was reduced to 97.79%, and a peak of polymethacrylic acid chloride was visible in the product chromatogram.

[0066] Comparative Example 1 3-Methacrylate cyclopentane sulfonate was prepared by a method substantially the same as that in Example 1, except that the crystallization solvent in step (2) was a mixed solvent of petroleum ether (24 ml) and toluene (12 ml). Recrystallization at -20°C failed to precipitate solid 3-methacrylate cyclopentane sulfonate product.

[0067] Comparative Example 2 3-Methacrylate cyclopentane sulfonate was prepared by a method substantially the same as that in Example 1, except that the recrystallization in step (2) was carried out at 0°C, resulting in only a small amount of solid precipitation. The resulting solid was dried at 0°C to a constant weight, yielding only 1.7 g of a white powder solid with a purity of 93.2%.

[0068] All documents mentioned in this application are cited as references in this application, just as each document is cited as reference separately. Unless they conflict with the application purpose and / or technical solution of this application, the cited documents involved in this application are cited in their entirety and for all purposes. When cited documents are involved in this application, the definitions of relevant technical features, terms, nouns, phrases, etc. in the cited documents are also cited. When cited documents are involved in this application, the examples and preferred embodiments of the cited relevant technical features may also be incorporated into this application as references, but are limited to the ability to implement this application. It should be understood that when the cited content conflicts with the description in this application, the present application shall prevail or be adaptively amended according to the description in this application.

[0069] The various technical features of the above-mentioned implementation modes and examples can be combined in any appropriate manner. In order to make the description concise, not all possible combinations of the various technical features in the above-mentioned implementation modes and examples are described. However, as long as there is no contradiction in the combination of these technical features, they should be considered to be within the scope of the description in this specification.

[0070] The embodiments described above only express several implementation methods of the present application, but they should not be understood as limiting the scope of the patent application. It should be pointed out that, for those of ordinary skill in the art, without departing from the concept of the present application, several variations and improvements can be made, which all fall within the scope of protection of the present application. In addition, it should be understood that after reading the above-mentioned teaching content of the present application, those skilled in the art can make various changes or modifications to the present application, and the equivalent forms obtained also fall within the scope of protection of the present application. It should also be understood that the technical solutions obtained by those skilled in the art through logical analysis, reasoning or limited experiments on the basis of the technical solutions provided in the present application are all within the scope of protection of the claims attached to the present application. Therefore, the scope of protection of the patent application of the present application shall be based on the attached claims, and the description can be used to interpret the content of the claims.

Claims

1. A method for preparing sulfolane methacrylate, characterized in that: The steps include: Under the conditions of a protective gas atmosphere and the presence of an organic base, 3-hydroxysulfolane and methacryloyl chloride are subjected to an esterification reaction in a first solvent, wherein the first solvent is a low-boiling-point organic solvent; After the esterification reaction is completed, the reaction solution is quenched and separated to obtain an organic layer liquid; The organic layer liquid is subjected to chromatography using a silica gel column to obtain an oily liquid; Crystallizing the oily liquid to obtain solid sulfolane methacrylate; The temperature of the crystallization treatment is -30°C to -10°C, and the crystallization solvent used is a mixed solvent of alkane and alcohol.

2. The preparation method according to claim 1, characterized in that Satisfy at least one of the following conditions (1) to (3): (1) The molar ratio of the 3-hydroxysulfolane to the methacryloyl chloride is 1:(1-2); (2) the molar ratio of the 3-hydroxysulfolane to the organic base is 1:(1-3); (3) The mass volume ratio (g / mL) of the 3-hydroxycyclopentane sulfone and the first solvent is 1:3-10.

3. The preparation method according to claim 1, characterized in that The temperature of the esterification reaction is 0° C. to 40° C., and the time is 1 to 6 hours.

4. The preparation method according to claim 1, characterized in that Satisfy at least one of the following conditions (1) to (2): (1) The organic base includes at least one of triethylamine, diisopropylethylamine, pyridine, 4-dimethylaminopyridine, 1,8-diazabicycloundec-7-ene, sodium methoxide, potassium tert-butoxide and lithium diisopropylamide; (2) The first solvent includes at least one of dichloromethane, tetrahydrofuran, and acetone.

5. The preparation method according to any one of claims 1 to 4, characterized in that Before the organic layer liquid is subjected to chromatography using a silica gel column, the organic layer liquid is washed with ethanol and saturated saline, and then dried.

6. The preparation method according to any one of claims 1 to 4, characterized in that The step of subjecting the organic layer liquid to chromatography using a silica gel column to obtain an oily liquid comprises: Concentrating the organic layer liquid to obtain a concentrate; Adsorbing the concentrate with silica gel powder to obtain a silica gel sample; The silica gel sample is loaded onto a silica gel column, and gradient eluted with a mixed solvent of petroleum ether and ethyl acetate to obtain an eluate; The eluate is concentrated to obtain the oily liquid.

7. The preparation method according to claim 6, characterized in that The step of adsorbing the concentrate with silica gel powder to obtain a silica gel sample comprises: dissolving the concentrate in a second solvent, adding silica gel powder and mixing to obtain a mixture; volatilizing the solvent in the mixture to obtain the silica gel sample; The second solvent is an ether organic solvent.

8. The preparation method according to claim 7, characterized in that The second solvent includes at least one of diethyl ether, isopropyl ether, methyl tert-butyl ether, tetrahydrofuran, dioxane and ethylene glycol monomethyl ether.

9. The preparation method according to any one of claims 1 to 4, 7 to 8, characterized in that In the crystallization solvent, the alkane includes at least one of petroleum ether, n-hexane, n-heptane, n-pentane, cyclohexane, methylcyclohexane and n-octane; and / or, The alcohol includes at least one of methanol, ethanol, isopropanol, n-butanol, ethylene glycol and glycerol.

10. The preparation method according to any one of claims 1 to 4, 7 to 8, characterized in that: In the crystallization solvent, the volume ratio of the alkane to the alcohol is (1.5-2.5):1.

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