A method for preparing 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester of olefinic acid

Abstract

This invention discloses a method for preparing 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester of olefinic acid, belonging to the field of chemical synthesis technology. The method includes: S1, enolizing γ-butyrolactone with cyclohexanone in the presence of an organic base to obtain an enol salt intermediate, then adding a Lewis acid complexing agent to form a zinc enol salt complex, followed by hydroxyalkylation in the presence of an acidic inhibitor to obtain an intermediate as shown in general formula 1; S2, esterifying the intermediate with an unsaturated acyl chloride as shown in formula 2 to obtain the target product. This invention not only provides a mild, highly selective, and precisely controllable synthetic route, but also simultaneously achieves a synergistic effect of high product purity, low single-metal impurity residue, and high yield, providing strong technical support for the large-scale industrial production and high-end applications of 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester photoresist monomers.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, and particularly relates to a method for preparing 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester of olefinic acid. Background Technology

[0002] Alkenyl 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester is a class of multifunctional photoresist monomers possessing a lactone ring, a cyclohexyl backbone, and polymerizable double bonds (C=C). The γ-butyrolactone structural unit in its molecular structure enhances adhesion to the substrate, the cyclohexyl unit increases the resin's rigidity and etching resistance, and the terminal polymerizable alkenyl double bond can participate in copolymerization reactions via free radical polymerization. Therefore, this type of monomer can serve as an ideal structural unit for constructing deep ultraviolet photoresist film-forming resins, and has significant application prospects in semiconductor photolithography processes.

[0003] Currently, methods for synthesizing photoresist resin monomers containing lactone rings have been reported in the literature. A classic route involves constructing an alicyclic skeleton using Diels-Alder cycloaddition, followed by oxidative lactonization and esterification to introduce polymerizable double bonds. For example, Chinese invention patent CN114085138A discloses a method for preparing photoresist resin monomers, which involves first performing depolymerization and epoxidation reactions, followed by lactonization and esterification, ultimately yielding a photoresist resin monomer containing a lactone ring. Chinese invention patent CN114315766A also discloses a method for preparing a photoresist resin monomer containing a lactone structure, obtaining the target monomer through multiple steps such as oxidative ring-opening and esterification. Although these multi-step synthetic routes can obtain the target product, the steps are lengthy, and the separation and purification of intermediates are complex, which is not conducive to large-scale industrial production.

[0004] Therefore, how to simplify the synthesis steps of photoresist resin monomers containing lactone rings, improve reaction yield, and reduce production costs has become a technical problem that urgently needs to be solved in this field. Summary of the Invention

[0005] The purpose of this invention is to solve the technical problems in existing methods for synthesizing photoresist resin monomers containing lactone rings, which involve lengthy steps and complex intermediate separation and purification operations, making it difficult to meet the requirements of large-scale industrial production. This invention provides a method for preparing 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester of olefinic acid, in order to achieve the technical goals of optimizing the synthesis route and reaction conditions, improving product yield and purity, and thus meeting the requirements of large-scale industrial production.

[0006] The technical solution adopted in this invention is: A method for preparing an olefinic acid 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester, the key of which is that it includes the following steps: S1. γ-Butyrolactone and cyclohexanone are subjected to an enolization reaction in the presence of an organic base to obtain an enol intermediate. Then, a Lewis acid complexing agent is added to form a zinc enol complex. The complex is then subjected to a hydroxyalkylation reaction in the presence of an acid inhibitor to obtain an intermediate as shown in general formula 1. S2. The intermediate obtained in step S1 is subjected to an esterification reaction with an unsaturated acyl chloride as shown in Formula 2 to obtain the above-mentioned 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester of olefinic acid, as shown in Formula 3. Formula 1; Formula 2; Formula 3; In Formulas 2 and 3, R is selected from alkenyl groups of C2 to C6.

[0007] Specifically, Equation 2 above can be any of the following structures: , , , .

[0008] Furthermore, the above-mentioned organic base includes lithium diisopropylamino and potassium hexamethyldisilamide, and the molar ratio of the above-mentioned γ-butyrolactone, lithium diisopropylamino and potassium hexamethyldisilamide is 1:(0.5-0.6):(0.5-0.6).

[0009] Furthermore, the Lewis acid complexing agent is ZnCl2, and the molar ratio of the Lewis acid complexing agent to γ-butyrolactone is (0.8–1.2):1.

[0010] Furthermore, the acidic inhibitor is phosphoric acid, and the molar ratio of the acidic inhibitor to γ-butyrolactone is (0.01-0.02):1.

[0011] Furthermore, the enolization reaction temperature is -40℃ to -30℃, and the reaction time is 20 min to 40 min; the hydroxyalkylation reaction temperature is -10℃ to 0℃, and the reaction time is 1.5 h to 2.5 h.

[0012] Specifically, in step S1 above, the order of adding each material is as follows: first, add the organic base to anhydrous tetrahydrofuran, cool to -40℃~-30℃, add a tetrahydrofuran solution of γ-butyrolactone, stir, then add a tetrahydrofuran solution of Lewis acid complexing agent, then add a tetrahydrofuran solution of cyclohexanone, and finally add an acid inhibitor.

[0013] Specifically, in step S2 above, the molar ratio of the intermediate to the unsaturated acyl chloride is 1:(1.2 to 2.4).

[0014] More specifically, the solvent for the above esterification reaction is dichloromethane, and the amount used is 1L to 2L of dichloromethane for 1mol of intermediate; the temperature of the above esterification reaction is 40℃ to 45℃, and the reaction time is 1.5h to 2.5h.

[0015] More specifically, the above esterification reaction is carried out in the presence of an acid-binding agent; the acid-binding agent is composed of 4-dimethylaminopyridine and triethylenediamine, and the molar ratio of 4-dimethylaminopyridine to triethylenediamine is 1:(20-40).

[0016] Compared with the prior art, the present invention has the following advantages: First, this invention employs a mixed alkali system composed of lithium diisopropylamino and potassium hexamethyldisilamide, combined with the synergistic effect of ZnCl2 as a Lewis acid complexing agent and phosphoric acid as an acid inhibitor, to construct a mild and efficient hydroxyalkylation reaction pathway. Specifically, the mixed alkali system of lithium diisopropylamino and potassium hexamethyldisilamide optimizes the aggregation state and reactivity of enol anions through the synergistic effect of lithium and potassium ions; the introduction of ZnCl2 forms a stable zinc enol salt complex, significantly reducing the nucleophilic activity of enol anions, thus allowing the reaction to proceed under mild conditions from -10°C to 0°C; phosphoric acid, as an acid inhibitor, utilizes its buffering properties as a multi-component medium-strong acid to precisely maintain the weakly acidic microenvironment of the reaction system, blocking side reactions such as the aldol condensation of cyclohexanone from the source. Therefore, this invention fundamentally solves the technical problems of hydroxyalkylation reactions requiring extremely low temperatures, numerous side reactions, and low yields, achieving a synergistic improvement in reaction selectivity and conversion efficiency.

[0017] Secondly, the preparation method of this invention enables the key quality indicators of the product to meet the high-end application standards of photoresist monomers. This is due to the ingenious design of the overall process of this invention: the mixed alkali system improves the regioselectivity of hydroxyalkylation, the dual regulation of zinc chloride complexation and phosphoric acid inhibition effectively reduces impurity generation, the post-treatment washing with disodium EDTA efficiently removes metal ions, and the synergistic catalytic and acid-binding effects of the combined acid-binding agents of 4-dimethylaminopyridine and triethylenediamine in the esterification reaction. The product prepared by this invention has high purity, low single metal impurities, and stable yield, which can fully meet the stringent requirements of semiconductor photolithography processes for ultra-high purity and single metal impurities in photoresist monomers.

[0018] Third, the preparation method of this invention has a wide process window and high substrate versatility. By reasonably adjusting the process parameters, the process of this invention exhibits excellent applicability to unsaturated acyl chloride substrates with different carbon chain lengths and double bond positions, including methacryloyl chloride, acryloyl chloride, 4-pentenoyl chloride, and 5-hexenoyl chloride, and the prepared products have stable quality. This provides an efficient and reliable technical basis for designing and synthesizing specific acrylate monomers to meet the performance requirements of different photoresist resins.

[0019] In summary, this invention not only provides a mild, highly selective, and precisely controllable synthesis route, but also simultaneously achieves a synergistic effect of high product purity, low single metal impurity residue, and high yield, providing strong technical support for the large-scale industrial production and high-end application of olefinic acid 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester photoresist monomers. Attached Figure Description

[0020] Figure 1 This is the high-performance liquid chromatogram of sample 1 of the present invention.

[0021] Figure 2 This is the high-performance gas chromatography-mass spectrometry (HPLC-MS) spectrum of sample 1 of the present invention.

[0022] Figure 3 This is the 1H NMR spectrum (¹H NMR) of sample 1 of this invention. Detailed Implementation

[0023] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0024] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0025] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0026] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0027] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0028] Unless otherwise specified in the examples, the standard conditions can be followed; unless the manufacturer of the reagents or instruments used is specified, they are all commercially available products.

[0029] Example 1 This embodiment prepares 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl esters of enoic acid, and the specific process is as follows: S1, hydroxyalkylation reaction: S1-1, formation of enolates: Under nitrogen protection, 100 mL of anhydrous tetrahydrofuran was added to a dry reactor, followed by the addition of 0.055 mol of lithium diisopropylamino (LDA) and 0.055 mol of potassium hexamethyldisilamide (KHMDS). The mixture was stirred at 300 rpm and cooled to -35 °C. A mixed solution of 0.1 mol of γ-butyrolactone and 30 mL of anhydrous tetrahydrofuran was slowly added dropwise. After the addition was complete, the mixture was stirred at 300 rpm for 30 min. The molar ratio of γ-butyrolactone, LDA and KHMDS is 1:0.55:0.55.

[0030] Formation of S1-2, zinc enol salt complex: While maintaining the temperature, 160 mL of a pre-prepared anhydrous tetrahydrofuran solution of ZnCl2 (ZnCl2 concentration of 0.5 mol / L) was slowly added dropwise. After the addition was complete, the mixture was stirred at 300 r / min for 30 min to form a stable zinc enol salt complex. During the addition of the anhydrous tetrahydrofuran solution of ZnCl2, the reaction solution gradually changed from colorless and transparent to a light yellow and transparent solution. The solution remained homogeneous and transparent, with no obvious precipitation or turbidity.

[0031] S1-3, Addition reaction of cyclohexanone: Maintain the temperature and slowly add a mixed solution of 0.125 mol cyclohexanone and 40 mL anhydrous tetrahydrofuran. After the addition is complete, add 0.0015 mol phosphoric acid as an acid inhibitor to the system. After the addition is complete, raise the temperature to -5℃ and carry out the hydroxyalkylation reaction at 300 r / min for 2 h.

[0032] S1-4, Post-hydroxyalkylation treatment: After the hydroxyalkylation reaction is completed, the reaction solution is slowly poured into 150 mL of pre-cooled 0.5 mol / L dilute hydrochloric acid. The pouring speed is controlled so that the internal temperature does not exceed 10 °C. After stirring for 10 min, the mixture is allowed to stand for 30 min and then separated. The aqueous phase was extracted once with 50 mL of ethyl acetate, and the organic phases were combined. The organic phase was washed once with 50 mL of 5% (w / w) EDTA disodium aqueous solution. After standing and separating, 10 g of anhydrous sodium sulfate was added to the organic phase, and the mixture was stirred and dried for 30 min. The mixture was then filtered, and the filtrate was concentrated under reduced pressure (0.09 MPa) in a 40 °C water bath until no distillation occurred. The filtrate was then rotary evaporated at 80 °C for 15 min using an oil pump to obtain the intermediate.

[0033] S2, Esterification reaction: S2-1, The addition and reaction of unsaturated acyl chlorides: Under nitrogen protection, 0.1 mol of the intermediate prepared in step S1-4, 150 mL of dichloromethane, and 0.3 mol of acid-binding agent were added to the reactor. 0.18 mol of methacryloyl chloride was slowly added dropwise at room temperature, and the temperature was raised to 43 °C for esterification reaction for 2 h. The acid-binding agent consists of 4-dimethylaminopyridine (DMAP) and triethylenediamine (DABCO) in a molar ratio of 1:30, with a total acid-binding agent dosage of 0.3 mol.

[0034] S2-2, Post-processing and product purification: After the reaction is complete, the liquid is cooled to 25°C, 100 mL of purified water is added to wash once, stirred for 15 min, and allowed to stand for 30 min before separation. Add 10g of anhydrous sodium sulfate to the organic phase and dry for 30min. Filter and concentrate the filtrate under reduced pressure (0.09MPa) in a 40℃ water bath until no distillation occurs to obtain the crude product. The crude product was purified by column chromatography, the target fractions were combined, and the product was concentrated to dryness under reduced pressure at 40°C. The residue was added with 1.5 times the volume of n-hexane, and the mixture was stirred at 2°C for 1 hour. The mixture was filtered, and the filter cake was dried in a vacuum drying oven at 40°C for 4 hours to obtain the product shown in Formula 4, which is denoted as Sample 1.

[0035] Formula 4 Example 2 S1, hydroxyalkylation reaction: S1-1, formation of enolates: Under nitrogen protection, 80 mL of anhydrous tetrahydrofuran was added to a dry reactor, followed by 0.06 mol LDA and 0.05 mol KHMDS. The mixture was stirred at 200 r / min and cooled to -30 °C. A mixed solution of 0.1 mol γ-butyrolactone and 20 mL of anhydrous tetrahydrofuran was slowly added dropwise. After the addition was complete, the mixture was stirred at 200 r / min for 20 min. The molar ratio of γ-butyrolactone, LDA and KHMDS is 1:0.6:0.5.

[0036] Formation of S1-2, zinc enol salt complex: Maintain the temperature and slowly add 200 mL of a pre-prepared anhydrous tetrahydrofuran solution of ZnCl2 (ZnCl2 concentration is 0.5 mol / L). After the addition is complete, stir at 200 r / min for 20 min to form a stable zinc enol salt complex.

[0037] S1-3, Addition reaction of cyclohexanone: Maintain the temperature and slowly add a mixed solution of 0.15 mol cyclohexanone and 30 mL anhydrous tetrahydrofuran. After the addition is complete, add 0.001 mol phosphoric acid as an acid inhibitor to the system. After the addition is complete, raise the temperature to 0℃ and carry out the hydroxyalkylation reaction at 200 r / min for 1.5 h.

[0038] S1-4, Post-hydroxyalkylation treatment: After the hydroxyalkylation reaction is complete, the reaction solution is slowly poured into 150 mL of pre-cooled 0.5 mol / L dilute hydrochloric acid (with the internal temperature controlled not to exceed 5 °C), stirred for 15 min, and then allowed to stand for 40 min before separation. The aqueous phase was extracted once with 40 mL of dichloromethane, and the organic phases were combined. The organic phase was washed once with 60 mL of 5% (w / w) EDTA disodium aqueous solution. After standing and separating, 12 g of anhydrous sodium sulfate was added to the organic phase, and the mixture was stirred and dried for 40 min. The mixture was then filtered, and the filtrate was concentrated under reduced pressure (0.08 MPa) in a 38°C water bath until no distillation occurred. The filtrate was then rotary evaporated at 78°C for 20 min using an oil pump to obtain the intermediate.

[0039] S2, Esterification reaction: S2-1, The addition and reaction of unsaturated acyl chlorides: Under nitrogen protection, 0.1 mol of the intermediate prepared in step S1-4, 200 mL of dichloromethane, and 0.4 mol of acid-binding agent were added to the reactor. 0.24 mol of methacryloyl chloride was slowly added dropwise at room temperature, and the temperature was raised to 45 °C for esterification reaction for 1.5 h. The acid-binding agent consists of DMAP and DABCO in a molar ratio of 1:20, with a total amount of 0.4 mol.

[0040] S2-2, Post-processing and product purification: After the esterification reaction is complete, the liquid is cooled to 20°C, 120 mL of saturated saline solution is added to wash once, stirred for 20 min, and allowed to stand for 40 min before separation. Add 12g of anhydrous sodium sulfate to the organic phase and dry for 40min. Filter and concentrate the filtrate under reduced pressure (0.08MPa) in a 38℃ water bath until no distillation occurs to obtain the crude product. The crude product was purified by column chromatography, the target fractions were combined, and the product was concentrated to dryness under reduced pressure at 38°C. The residue was added with 1.5 times the volume of petroleum ether, and the mixture was slurried at 0°C for 1.5 hours. The mixture was then filtered, and the filter cake was dried in a vacuum drying oven at 45°C for 3 hours to obtain the product shown in Formula 4, which is designated as Sample 2.

[0041] Example 3 S1, hydroxyalkylation reaction: S1-1, formation of enolates: Under nitrogen protection, 150 mL of anhydrous tetrahydrofuran was added to a dry reactor, followed by 0.05 mol LDA and 0.06 mol KHMDS. The mixture was stirred at 400 r / min and cooled to -40 °C. A mixed solution of 0.1 mol γ-butyrolactone and 40 mL of anhydrous tetrahydrofuran was slowly added dropwise. After the addition was complete, the mixture was stirred at 400 r / min for 40 min. The molar ratio of γ-butyrolactone, LDA and KHMDS is 1:0.5:0.6.

[0042] Formation of S1-2, zinc enol salt complex: While maintaining the temperature, slowly add 240 mL of a pre-prepared anhydrous tetrahydrofuran solution of ZnCl2 (ZnCl2 concentration of 0.5 mol / L). After the addition is complete, stir at 400 r / min for 40 min to form a stable zinc enol salt complex.

[0043] S1-3, Addition reaction of cyclohexanone: Maintain the temperature and slowly add a mixed solution of 0.1 mol cyclohexanone and 50 mL anhydrous tetrahydrofuran. After the addition is complete, add 0.002 mol phosphoric acid as an acid inhibitor to the system. After the addition is complete, raise the temperature to -10℃ and carry out the hydroxyalkylation reaction at 400 r / min for 2.5 h.

[0044] S1-4, Post-hydroxyalkylation treatment: After the hydroxyalkylation reaction is completed, the reaction solution is slowly poured into 180 mL of pre-cooled 0.5 mol / L dilute hydrochloric acid, the internal temperature is controlled not to exceed 8 °C, and the mixture is stirred for 10 min and then allowed to stand for 35 min before separation. The aqueous phase was extracted once with 45 mL of methyl tert-butyl ether, and the organic phases were combined. The organic phase was washed once with 70 mL of 5% (w / w) EDTA disodium aqueous solution. After standing and separation, 15 g of anhydrous sodium sulfate was added to the organic phase, and the mixture was stirred and dried for 35 min. The mixture was then filtered, and the filtrate was concentrated under reduced pressure (0.095 MPa) in a 42 °C water bath until no distillation occurred. The filtrate was then rotary evaporated at 82 °C for 18 min using an oil pump to obtain the intermediate.

[0045] S2, Esterification reaction: S2-1, The addition and reaction of unsaturated acyl chlorides: Under nitrogen protection, 0.1 mol of the intermediate prepared in step S1-4, 100 mL of dichloromethane, and 0.2 mol of acid-binding agent were added to the reactor. 0.12 mol of methacryloyl chloride was slowly added dropwise at room temperature, and the temperature was raised to 40 °C for esterification reaction for 2.5 h. The acid-binding agent consists of DMAP and DABCO in a molar ratio of 1:40, with a total amount of 0.2 mol of acid-binding agent.

[0046] S2-2, Post-processing and product purification: After the esterification reaction is complete, the liquid is cooled to 22°C, 130 mL of 5% sodium bicarbonate aqueous solution is added to wash once, stirred for 10 min, and allowed to stand for 35 min before separation. Add 15g of anhydrous sodium sulfate to the organic phase and dry for 35min. Filter and concentrate the filtrate under reduced pressure (0.095MPa) in a 42℃ water bath until no distillation occurs to obtain the crude product. The crude product was purified by column chromatography, the target fractions were combined, and the product was concentrated to dryness under reduced pressure at 42°C. The residue was added to a mixed solvent of n-hexane and ethyl acetate (volume ratio 10:1), and the mixture was stirred at 5°C for 1.2 h. The mixture was filtered, and the filter cake was dried in a vacuum drying oven at 40°C for 4.5 h to obtain the product shown in Formula 4, which is denoted as Sample 3.

[0047] Example 4 This embodiment prepares 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester compounds of olefinic acid. The specific preparation process is the same as in Example 1, except that in step S2-1, acryloyl chloride is used in place of methacryloyl chloride in an equal amount. The subsequent steps are the same, and the product shown in Formula 5 is obtained, which is denoted as Sample 4.

[0048] Formula 5 Example 5 In this embodiment, 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester compounds of enoic acid were prepared. The specific process was the same as in Example 1, except that in step S2-1, an equal amount of 4-pentenoyl chloride was used instead of methacryloyl chloride, and the esterification reaction time was extended to 2.5 h. The subsequent steps were the same, and the product shown in Formula 6 was prepared, which was denoted as Sample 5.

[0049] Formula 6 Example 6 This embodiment prepares 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester compounds of enoic acid. The specific process is the same as in Example 1, except that in step S2-1, an equal amount of 5-hexenoyl chloride is used instead of methacryloyl chloride, and the esterification reaction temperature is increased to 45°C and the reaction time is extended to 2.5 h. The subsequent steps are the same, and the product shown in Formula 7 is prepared, which is denoted as Sample 6.

[0050] Formula 7 Comparative Example 1 This comparative example provides a comparative preparation method, the specific implementation of which is the same as in Example 1, except that: in step S1-1, the mixed base of 0.055 mol LDA and 0.055 mol KHMDS is replaced with 0.11 mol of a single base LDA, that is, the molar ratio of γ-butyrolactone to LDA is 1:1.1, and KHMDS is not added; the rest of the operation remains unchanged; the subsequent steps are the same as in Example 1, and the product obtained is recorded as control 1.

[0051] Comparative Example 2 This comparative example provides a comparative preparation method, the specific implementation of which is the same as in Example 1, except that: in step S1-1, the mixed base of 0.055 mol LDA and 0.055 mol KHMDS is replaced with 0.11 mol of a single base KHMDS, that is, the molar ratio of γ-butyrolactone to KHMDS is 1:1.1, and LDA is not added; the rest of the operation remains unchanged, and the subsequent steps are the same as in Example 1. The product obtained is recorded as control 2.

[0052] Comparative Example 3 This comparative example provides a comparative preparation method, the specific implementation of which is the same as in Example 1, except that: in step S1-1, the mixed base of 0.055 mol LDA and 0.055 mol KHMDS is replaced with 0.11 mol hexamethyldisilamide lithium (LiHMDS), that is, the molar ratio of γ-butyrolactone to LiHMDS is 1:1.1; the rest of the operation remains unchanged, and the subsequent steps are the same as in Example 1. The product obtained is recorded as control 3.

[0053] Comparative Example 4 This comparative example provides a comparative preparation method, the specific implementation of which is the same as in Example 1, the difference being that: in steps S1-2, the addition of anhydrous tetrahydrofuran solution of ZnCl2 is omitted, that is, no zinc enol salt complex is formed; the remaining operations remain unchanged, and the subsequent steps are the same as in Example 1, and the product obtained is recorded as control 4.

[0054] Comparative Example 5 This comparative example provides a comparative preparation method, the specific implementation of which is the same as in Example 1, except that: in step S1-2, ZnCl2 is replaced with an equal amount of MgCl2, that is, 160 mL of a pre-prepared 0.5 mol / L MgCl2 anhydrous tetrahydrofuran solution is added dropwise; the rest of the operation remains unchanged, and the subsequent steps are the same as in Example 1, and the product obtained is recorded as control 5.

[0055] Comparative Example 6 This comparative example provides a comparative preparation method, the specific implementation of which is the same as in Example 1, except that: in steps S1-3, phosphoric acid is replaced with an equal amount of formic acid (0.0015 mol) as an acid inhibitor; the remaining operations remain unchanged; the subsequent steps are the same as in Example 1, and the product obtained is recorded as control 6.

[0056] Comparative Example 7 This comparative example provides a comparative preparation method, the specific implementation of which is the same as in Example 1, except that: in step S2-1, the acid-binding agent is replaced by 0.3 mol of a single acid-binding agent, triethylamine, instead of a combination of DMAP and DABCO (molar ratio 1:30, total amount 0.3 mol), i.e., no DMAP and DABCO are added; the rest of the operation remains unchanged; the subsequent steps are the same as in Example 1, and the product obtained is recorded as control 7.

[0057] Comparative Example 8 This comparative example provides a comparative preparation method, the specific implementation of which is the same as in Example 1, except that: in step S2-1, the molar ratio of DMAP to DABCO in the acid-binding agent is adjusted to 1:5 (i.e., 0.05 mol of DMAP and 0.25 mol of DABCO, with the total amount still being 0.3 mol); the remaining operations remain unchanged; the subsequent steps are the same as in Example 1, and the product obtained is designated as reference standard 8.

[0058] Comparative Example 9 This comparative example provides a comparative preparation method, the specific implementation of which is the same as in Example 1, except that the order of adding materials is adjusted, that is, the order of S1-1 and S1-3 is interchanged, and cyclohexanone is added first and then γ-butyrolactone is added. The specific operation is as follows: Under nitrogen protection, anhydrous tetrahydrofuran is added to a dry reactor, followed by 0.055 mol LDA and 0.055 mol KHMDS. The mixture is stirred at 300 r / min and cooled to -35℃. A mixed solution of 0.125 mol cyclohexanone and 40 mL anhydrous tetrahydrofuran is slowly added dropwise. After the addition is complete, the mixture is stirred at 300 r / min for 30 min. Then, a mixed solution of 0.1 mol γ-butyrolactone and 30 mL anhydrous tetrahydrofuran is slowly added dropwise. The remaining operations S1-2, S1-3, and S1-4 remain unchanged.

[0059] In the post-processing of the S1-4 hydroxyalkylation reaction, the intermediate was almost impossible to separate (yield <5%), so the subsequent S2 esterification reaction could not be carried out, and the final product could not be obtained.

[0060] Analysis and Testing The purity of each sample or reference standard was analyzed using high performance liquid chromatography (HPLC), and the content of single metal impurities in the sample or reference standard was determined. The product yield was also calculated. The results are shown in Table 1.

[0061] Product yield = Actual weight of the product obtained (g) / Theoretical yield calculated based on the amount of γ-butyrolactone used (g) × 100%.

[0062] In addition, the structure was confirmed using high-performance gas chromatography-mass spectrometry and nuclear magnetic resonance (NMR). The relevant test chromatograms for sample 1 are shown below. Figures 1-3 .

[0063] Table 1: Summary Table of Product Yield and Quality Analysis As shown in Table 1, the purity of samples 1-6 prepared by this invention is consistently 99.5% or higher, the content of single metal impurities is effectively controlled within 65 ppb, and the product yield is consistently 88.7% or higher. This demonstrates that the preparation method of this invention exhibits excellent reaction selectivity and conversion efficiency for unsaturated acyl chlorides of different structures, suppresses side reactions, and facilitates subsequent removal of impurities and metal impurities, ensuring that the product quality meets the high-end application requirements of photoresist monomers.

[0064] Among them, Examples 1 to 3, which used methacryloyl chloride as a substrate, showed that the purity, single metal impurities, and yield of the products were all maintained at excellent levels, which fully demonstrates that the process of the present invention is stable and reliable and has good process controllability and reproducibility.

[0065] Example 4 used acryloyl chloride as a substrate, Example 5 used 4-pentenoyl chloride as a substrate, and Example 6 used 5-hexenoyl chloride as a substrate, representing unsaturated acrylic chlorides with different carbon chain lengths and double bond positions, respectively. Table 1 shows that high-purity and high-yield products were obtained using different unsaturated acrylic chlorides as substrates, demonstrating the broad applicability of the method of this invention.

[0066] In contrast, reference standards 1-3 were used to investigate the effects of single LDA, single KHMDS, and LiHMDS as substitutes for the LDA and KHMDS mixed alkali of this invention. The results showed that using single LDA reduced the yield to 85.1%, single KHMDS to 78.3%, and LiHMDS to only 72.2%. The purities of the three decreased to 99.2%, 98.7%, and 98.4%, respectively, and the single metal impurities all increased to over 70 ppb. This demonstrates that the LDA and KHMDS mixed alkali system has a significant synergistic effect on improving reaction selectivity and yield, and controlling single metal impurities in the product, while other strong alkalis such as LiHMDS cannot achieve the same technical effect.

[0067] In the preparation of reference standard 4, omitting ZnCl2 during the process resulted in a sharp drop in yield to 62.5%, purity to 97.8%, and a single metal impurity increase to 82 ppb. This indicates that the lack of ZnCl2 to complex and stabilize the enol salt led to a rapid increase in side reactions at reaction temperatures ranging from -10°C to 0°C. Reference standard 5, prepared by replacing ZnCl2 with MgCl2, also showed significantly lower yield and purity than in Example 1, further demonstrating the irreplaceable role of ZnCl2 as a Lewis acid complexing agent.

[0068] Reference standard 6, using formic acid instead of phosphoric acid, had lower yields and purity than Example 1, and higher levels of single-metal impurities. This is because formic acid, being a monoprotic weak acid, lacks the buffering capacity of phosphoric acid's fractional ionization, making it difficult to stabilize the pH within the optimal range for inhibiting cyclohexanone self-condensation. This results in excessive protonation of the enol anion, reducing the activity of the main reaction. Simultaneously, the residual strong basic impurities cannot be effectively neutralized, preventing the complete blocking of the side reaction chain. In contrast, phosphoric acid, with its superior buffering properties, achieved the best inhibitory effect.

[0069] Reference standard 7, prepared by replacing the combination of DMAP and DABCO with the conventional organic base triethylamine, had a yield of only 76.8%, a purity of 98.1%, and a single metal impurity of 79 ppb. Reference standard 8, prepared by adjusting the ratio of DMAP to DABCO to 1:5, also showed significantly lower yield and purity than Example 1, with a significantly higher single metal impurity level. This demonstrates that the synergistic catalytic and acid-binding effects of DMAP and DABCO, as well as their specific ratio range, are key to efficient esterification reactions and ensuring high product purity and low single metal impurities.

[0070] Comparative Example 9 altered the feeding sequence during implementation, causing cyclohexanone to preferentially undergo its own aldol condensation, resulting in an extremely low intermediate yield and making subsequent esterification impossible. This demonstrates that the feeding sequence of first activating γ-butyrolactone and then adding cyclohexanone is a prerequisite for successful hydroxyalkylation.

[0071] In summary, the technical solution of this invention is a holistic solution in which all elements work synergistically and are indispensable. Through the organic integration of multiple technical means, including a mixed alkali system, ZnCl2 complexation, phosphoric acid inhibition, a specific feeding sequence, and an optimized combination of acid-binding agents, the efficient and highly selective preparation of 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl esters of olefinic acid under mild conditions has been successfully achieved, providing a reliable technical approach for the large-scale industrial production of photoresist monomers.

[0072] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A method for preparing 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester of enoic acid, characterized in that, Includes the following steps: S1. γ-Butyrolactone and cyclohexanone are subjected to an enolization reaction in the presence of an organic base to obtain an enol intermediate. Then, a Lewis acid complexing agent is added to form a zinc enol complex. The complex is then subjected to a hydroxyalkylation reaction in the presence of an acid inhibitor to obtain an intermediate as shown in general formula 1. S2. The intermediate obtained in step S1 is subjected to an esterification reaction with an unsaturated acyl chloride as shown in Formula 2 to obtain the 1-(2-oxotetrahydrofuran-3-yl)cyclohexyl ester of olefinic acid, as shown in Formula 3. Formula 1; Formula 2; Formula 3; In Formulas 2 and 3, R is selected from alkenyl groups of C2 to C6.

2. The preparation method according to claim 1, characterized in that, Equation 2 can be any of the following structures: ， ， ， 。 3. The preparation method according to claim 1, characterized in that, The organic base comprises lithium diisopropylamino and potassium hexamethyldisilamide, and the molar ratio of γ-butyrolactone, lithium diisopropylamino and potassium hexamethyldisilamide is 1:(0.5-0.6):(0.5-0.6).

4. The preparation method according to claim 1, characterized in that, The Lewis acid complexing agent is ZnCl2, and the molar ratio of the Lewis acid complexing agent to γ-butyrolactone is (0.8-1.2):

1.

5. The preparation method according to claim 1, characterized in that, The acidic inhibitor is phosphoric acid, and the molar ratio of the acidic inhibitor to γ-butyrolactone is (0.01-0.02):

1.

6. The preparation method according to claim 1, characterized in that, The enolization reaction temperature is -40℃ to -30℃, and the reaction time is 20 min to 40 min; the hydroxyalkylation reaction temperature is -10℃ to 0℃, and the reaction time is 1.5 h to 2.5 h.

7. The preparation method according to claim 1, characterized in that, In step S1, the order of adding each material is as follows: first, add the organic base to anhydrous tetrahydrofuran, cool to -40℃~-30℃, add a tetrahydrofuran solution of γ-butyrolactone, stir, add a tetrahydrofuran solution of Lewis acid complexing agent, then add a tetrahydrofuran solution of cyclohexanone, and finally add an acid inhibitor.

8. The preparation method according to claim 1, characterized in that, In step S2, the molar ratio of the intermediate to the unsaturated acyl chloride is 1:(1.2 to 2.4).

9. The preparation method according to claim 1, characterized in that, The solvent for the esterification reaction is dichloromethane, and the amount used is 1L to 2L of dichloromethane for every 1mol of intermediate; the esterification reaction temperature is 40℃ to 45℃, and the reaction time is 1.5h to 2.5h.

10. The preparation method according to claim 1, characterized in that, The esterification reaction is carried out in the presence of an acid-binding agent; the acid-binding agent is composed of 4-dimethylaminopyridine and triethylenediamine, and the molar ratio of 4-dimethylaminopyridine to triethylenediamine is 1:(20-40).

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