Preparation method of imidazole carboxylic ester

Abstract

The invention discloses a preparation method of imidazole carboxylic ester, and belongs to the technical field of chemical synthesis.The preparation method comprises the steps that N, N '-carbonyldiimidazole and a hydroxyl-containing compound shown in the formula 1 react under the catalysis of a catalyst N-methylimidazole, the reaction temperature and the reaction time are controlled, and an imidazole carboxylic ester compound shown in the formula 2 is obtained; according to the invention, N-methylimidazole is adopted as an exclusive catalyst, and a pre-activation step and a mixed solvent system are combined to construct an efficient catalysis path, so that a synthesis path which is high in selectivity and can be accurately controlled is provided, and synergy of ultra-high purity, extremely low moisture residue and high yield of the product is synchronously realized; effective technical support is provided for development and application of the imidazole carboxylic ester compound in the high-end field.

Description

Technical Field

[0001] This invention belongs to the field of chemical synthesis technology, and particularly relates to a method for preparing imidazole carboxylic acid ester. Background Technology

[0002] Imidazole carboxylic esters are an important class of fine chemical intermediates and products. Their active acyl imidazole units possess high reactivity and good functional group compatibility, making them widely used in numerous fields such as pharmaceutical synthesis, polymer materials, and electrochemistry. Particularly in the electrochemical field, such as lithium-ion battery electrolytes, these compounds serve as key additives in constructing stable electrode / electrolyte interface films, significantly improving battery cycle life and safety performance.

[0003] The synthetic route for this type of compound is well-established, involving the reaction of N,N'-carbonyldiimidazole with alcohols. This reaction requires no external catalyst and can be carried out at relatively low temperatures. However, the efficiency of this catalytically undependent reaction is limited. The reaction inevitably leads to the self-decomposition of N,N'-carbonyldiimidazole, resulting in side reactions such as product degradation or dimerization. This results in the product being contaminated with various impurities, making it difficult to improve purity.

[0004] Currently, some reports utilize conventional alkaline catalysts such as triethylamine or potassium hydroxide for reaction catalysis. The core objective is to activate the hydroxyl protons of alcohols, promoting their deprotonation to enhance the nucleophilicity of oxygen atoms and thus increase the reaction rate. However, the alkaline environment introduced by such catalysts raises another issue: it amplifies the sensitivity of the reaction system to trace amounts of moisture, exacerbating the hydrolysis of N,N'-carbonyldiimidazole and reactive intermediates, generating large amounts of imidazole byproducts that are difficult to completely separate. Simultaneously, alkaline conditions may also corrode alcohol substrates containing sensitive functional groups. Although the reaction rate is increased, the introduction of new impurity sources and the exacerbation of side reactions make it difficult to improve product purity. Consequently, the purity of products obtained by existing methods is typically difficult to consistently exceed 99.8%. While this meets the needs of general chemical production, for high-end applications such as electronic chemicals, the purity needs to be consistently above 99.7%, where existing methods fall short.

[0005] Therefore, developing a preparation method that can achieve efficient and highly selective conversion under mild conditions, suppress hydrolysis side reactions from the source, and achieve precise control of impurities has become a technical challenge to overcome the bottleneck of this series of products in high-end applications, especially in the field of electrochemistry. Summary of the Invention

[0006] The purpose of this invention is to solve the problem that in existing methods for synthesizing imidazole carboxylic acid esters, it is difficult to simultaneously achieve both reaction efficiency and product purity, resulting in a product purity that is difficult to consistently reach above 99.7%. This invention provides a method for preparing imidazole carboxylic acid esters to achieve efficient and highly selective conversion under mild conditions, thereby suppressing side reactions and precisely controlling impurities.

[0007] The technical solution adopted in this invention is a method for preparing imidazole carboxylic acid esters. The key is to react N,N'-carbonyldiimidazole with the compound containing hydroxyl groups shown in Formula 1 under the catalysis of N-methylimidazole, and control the reaction temperature and reaction time to obtain the imidazole carboxylic acid ester compound shown in Formula 2. Wherein, R is selected from alkyl groups with 1 to 10 substituted or unsubstituted carbon atoms, alkenyl groups with 2 to 10 substituted or unsubstituted carbon atoms, and alkynyl groups with 2 to 10 substituted or unsubstituted carbon atoms; The substituents mentioned above are at least one of ether, cyano, nitro, halogen, and aromatic ring. Formula 1; Equation 2.

[0008] Furthermore, R is selected from alkyl groups with 1 to 6 substituted or unsubstituted carbon atoms, alkenyl groups with 2 to 6 substituted or unsubstituted carbon atoms, and alkynyl groups with 2 to 6 substituted or unsubstituted carbon atoms; the substituents mentioned above are at least one of fluorine, chlorine, bromine, iodine, and phenyl.

[0009] Specifically, the molar ratio of the above-mentioned hydroxyl-containing compound, N,N'-carbonyldiimidazole, and N-methylimidazole is 1:(1.02~1.20):(0.015~0.025).

[0010] Specifically, the reaction temperature for the above reaction is -5℃ to 10℃, and the reaction time is 2h to 4h.

[0011] Furthermore, the above reaction requires prior catalytic activation of N,N'-carbonyldiimidazole and N-methylimidazole in a mixed reaction solvent before adding a hydroxyl-containing compound to carry out the reaction.

[0012] Furthermore, the above-mentioned mixed reaction solvent is a mixture of dichloromethane and tetrahydrofuran in a volume ratio of (90-100):5.

[0013] Specifically, the amount of mixed solvent used is 95 mL to 105 mL for each mole of a compound containing a hydroxyl group.

[0014] Specifically, the above catalytic activation is carried out at a temperature of -10℃ to 0℃ for a time of 20 min to 40 min.

[0015] More specifically, the method of adding the hydroxyl-containing compound is as follows: the hydroxyl-containing compound is added to dichloromethane at a ratio of 1 mol:(50 mL to 100 mL) to prepare a dichloromethane solution containing the hydroxyl-containing compound, and the above dichloromethane solution containing the hydroxyl-containing compound is added dropwise to the mixed reaction solvent.

[0016] Preferably, the dropping time of the dichloromethane solution containing the hydroxyl group is controlled to be 30 min to 60 min.

[0017] Compared with the prior art, the present invention has the following advantages: First, this invention employs N-methylimidazole as a dedicated catalyst and combines it with a pre-activation step and a mixed solvent system to construct a novel and highly efficient catalytic pathway. N-methylimidazole not only effectively catalyzes the reaction, but its structural similarity to the inherent byproduct imidazole further facilitates the suppression of free imidazole byproduct formation at the source. Furthermore, the pre-activation step of the catalyst with N,N'-carbonyldiimidazole at low temperature ensures the formation of a highly active catalytic intermediate. This catalytic system fundamentally solves the technical difficulties of low efficiency in catalyst-free routes and the exacerbation of hydrolysis side reactions in conventional base catalytic routes, thereby improving the reaction's activity and selectivity.

[0018] Secondly, the preparation method of this invention enables the key quality indicators of the product to consistently meet high-end application standards. This is not only due to the highly selective catalytic process designed in this invention, but also inseparable from the precise process control of this invention. Ultimately, this is reflected in the fact that the purity, moisture content, and yield of the products in all embodiments of this invention are comprehensively superior to the existing technology level, fully meeting the stringent requirements of the electronic chemicals and other fields for ultra-high purity and trace moisture control of materials.

[0019] Third, the preparation method of this invention provides a wide process range and higher substrate versatility. Through the rational design of key parameters such as temperature and material ratio, this process exhibits excellent adaptability to a variety of structurally significantly different alcohol substrates, including straight-chain primary alcohols, sterically hindered secondary alcohols, and those with strong electron-withdrawing groups or sensitive unsaturated bonds. The products with different structures prepared are of stable quality. This provides an efficient and reliable technical basis for designing and synthesizing specific imidazole carboxylic acid ester functional molecules to meet different performance requirements.

[0020] In summary, this invention not only provides a highly efficient, selective, and precisely controllable synthetic route, but also simultaneously achieves the synergistic effect of ultra-high product purity, extremely low moisture residue, and high yield, providing effective technical support for the development and application of this imidazole carboxylic acid ester compound in high-end fields. Attached Figure Description

[0021] Figure 1This is a high-performance gas chromatogram of sample 1 of the product of this invention.

[0022] Figure 2 This is the high-performance gas chromatogram of sample 4 of the product of this invention.

[0023] Figure 3 This is the high-performance gas chromatogram of sample 5 of the product of this invention.

[0024] Figure 4 This is a high-performance gas chromatography-mass spectrometry (HPLC-MS) spectrum of sample 1 of the present invention.

[0025] Figure 5 This is a high-performance gas chromatography-mass spectrometry (HPLC-MS) spectrum of sample 4 of the present invention.

[0026] Figure 6 This is a high-performance gas chromatography-mass spectrometry (HPLC-MS) spectrum of sample 5 of the present invention.

[0027] Figure 7 This is the 1H NMR spectrum of sample 1 of the product of this invention.

[0028] Figure 8 This is the 1H NMR spectrum of sample 4 of the present invention.

[0029] Figure 9 This is the 1H NMR spectrum of sample 5 of the present invention. Detailed Implementation

[0030] 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.

[0031] 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.

[0032] 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.

[0033] 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.

[0034] 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.

[0035] Unless otherwise specified in the examples, the procedures can be followed according to conventional conditions; unless the manufacturers of the reagents or instruments used are specified, they are all conventional products that can be purchased commercially.

[0036] Example 1 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 3 are prepared using N,N'-carbonyldiimidazole and cyclopropanol. The specific process is as follows: S1. Construction and activation of the catalytic system: In a dry reaction flask, add 0.105 mol of N,N'-carbonyldiimidazole and 0.002 mol of N-methylimidazole (the molar ratio of the hydroxyl-containing compound, N,N'-carbonyldiimidazole and N-methylimidazole is 1:1.05:0.02), and add 100 mL of a mixed solvent, which is composed of 95 mL of dichloromethane and 5 mL of tetrahydrofuran. Turn on the mixer and set the speed to 300 rpm to ensure the materials are mixed evenly; Nitrogen was continuously introduced into the system to replace the air three times, and a slight positive pressure protection was maintained in subsequent operations, that is, a steady and slow stream of bubbles continuously emerged from the outlet bubbler; Cool the system to -5°C, and at this temperature, keep stirring to carry out catalytic activation for 30 minutes.

[0037] S2. Controlled dropwise addition of a dichloromethane solution containing a hydroxyl group: 0.100 mol of cyclopropane methanol was mixed with 7.5 mL of anhydrous dichloromethane to obtain a dichloromethane solution containing a hydroxyl group. After activation in step S1, continue to maintain low temperature and stirring, and slowly add a dichloromethane solution containing hydroxyl compounds, controlling the dropping rate so that the entire dropping process takes 45 minutes, and the temperature during the dropping process is controlled not to exceed 0℃.

[0038] S3, Reaction: After the addition is complete, control the reaction system within the temperature range of 0℃, maintain the stirring speed and continue stirring for 3 hours to ensure the reaction is complete; After the reaction is complete, allow the reaction solution to return to room temperature naturally.

[0039] S4. Post-processing: Quench the reaction solution with 100 mL of ice water, allow it to stand and separate into layers, retain the lower organic phase, extract the aqueous phase once with 30 mL of dichloromethane, and combine the organic phases. The combined organic phases were washed once with 50 mL of 0.1 mol / L dilute hydrochloric acid solution to remove any possible residual N-methylimidazole. Then, wash the organic phase twice with 100 mL of ice water; Anhydrous sodium sulfate was added to the washed organic phase for drying. After filtration, the filtrate was retained and concentrated under reduced pressure at 30°C to remove most of the dichloromethane and tetrahydrofuran, yielding a viscous crude product. The crude product was transferred to a distillation flask and distilled under reduced pressure at a vacuum of 90 Pa. The fraction corresponding to the boiling range of the product was collected to obtain the final product as shown in Formula 3, which is denoted as Sample 1.

[0040] Formula 3 Example 2 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 3 are prepared using N,N'-carbonyldiimidazole and cyclopropanol. The specific process is as follows: S1. Construction and activation of the catalytic system: In a dry reaction flask, add 0.120 mol of N,N'-carbonyldiimidazole and 0.0015 mol of N-methylimidazole (the molar ratio of the hydroxyl-containing compound, N,N'-carbonyldiimidazole and N-methylimidazole is 1:1.20:0.015), and add 105 mL of a mixed solvent, which is composed of 100 mL of dichloromethane and 5 mL of tetrahydrofuran. Turn on the mixer and set the speed to 400 rpm to ensure the materials are mixed evenly; Nitrogen was continuously introduced into the system to replace the air three times, and a slight positive pressure protection was maintained in subsequent operations, that is, a steady and slow stream of bubbles continuously emerged from the outlet bubbler; Cool the system to -10°C and carry out catalytic activation by stirring at this temperature for 40 minutes.

[0041] S2. Controlled dropwise addition of a dichloromethane solution containing a hydroxyl group: 0.100 mol of cyclopropane methanol was mixed with 5 mL of anhydrous dichloromethane to obtain a dichloromethane solution containing a hydroxyl group. After activation in step S1, continue to maintain low temperature and stirring, and slowly add a dichloromethane solution containing hydroxyl compounds, controlling the dropping rate so that the entire dropping process takes 30 minutes, and the temperature during the dropping process is controlled not to exceed 0℃.

[0042] S3, Reaction: After the addition is complete, the reaction system is kept at a temperature of -5℃, and the stirring speed is maintained and the reaction is continuously stirred for 4 hours to ensure that the reaction is complete. After the reaction is complete, allow the reaction solution to return to room temperature naturally.

[0043] S4. Post-processing: Quench the reaction solution with 90 mL of ice water, allow it to stand and separate into layers, retain the lower organic phase, extract the aqueous phase once with 35 mL of dichloromethane, and combine the organic phases. The combined organic phases were washed once with 45 mL of 0.1 mol / L dilute hydrochloric acid solution to remove any possible residual N-methylimidazole. The organic phase was then washed twice with 100 mL of ice water. Anhydrous magnesium sulfate was added to the washed organic phase and dried. After filtration, the filtrate was retained and concentrated under reduced pressure at 20°C to remove most of the dichloromethane and tetrahydrofuran, yielding a viscous crude product. The crude product was transferred to a distillation flask and distilled under reduced pressure at a vacuum of 80 Pa. The fraction corresponding to the boiling range of the product was collected to obtain the final product as shown in Formula 3, which is denoted as Sample 2.

[0044] Example 3 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 3 are prepared using N,N'-carbonyldiimidazole and cyclopropanol. The specific process is as follows: S1. Construction and activation of the catalytic system: In a dry reaction flask, add 0.102 mol of N,N'-carbonyldiimidazole and 0.0025 mol of N-methylimidazole (the molar ratio of the hydroxyl-containing compound, N,N'-carbonyldiimidazole and N-methylimidazole is 1:1.02:0.025), and add 95 mL of a mixed solvent, which is composed of 90 mL of dichloromethane and 5 mL of tetrahydrofuran. Turn on the mixer and set the speed to 200 rpm to ensure the materials are mixed evenly; Nitrogen was continuously introduced into the system to replace the air three times, and a slight positive pressure protection was maintained in subsequent operations, that is, a steady and slow stream of bubbles continuously emerged from the outlet bubbler; Cool the system to 0°C, and at this temperature, keep stirring to carry out catalytic activation for 20 minutes.

[0045] S2. Controlled dropwise addition of a dichloromethane solution containing a hydroxyl group: 0.100 mol of cyclopropane methanol was mixed with 10 mL of anhydrous dichloromethane to obtain a dichloromethane solution containing a hydroxyl group. After activation in step S1, continue to maintain low temperature and stirring, and slowly add a dichloromethane solution containing hydroxyl compounds, controlling the dropping rate so that the entire dropping process takes 60 minutes, and the temperature during the dropping process is controlled not to exceed 0℃.

[0046] S3, Reaction: After the addition is complete, the reaction system is kept within a temperature range of 10°C, and the stirring speed is maintained and the reaction is continuously stirred for 2 hours to ensure that the reaction is complete. After the reaction is complete, allow the reaction solution to return to room temperature naturally.

[0047] S4. Post-processing: Quench the reaction solution with 110 mL of ice water, allow it to stand and separate into layers, retain the lower organic phase, extract the aqueous phase once with 25 mL of dichloromethane, and combine the organic phases. The combined organic phases were washed once with 55 mL of 0.1 mol / L dilute hydrochloric acid solution to remove any possible residual N-methylimidazole. The organic phase was then washed twice with 100 mL of ice water. Anhydrous sodium sulfate was added to the washed organic phase for drying. After filtration, the filtrate was retained and concentrated under reduced pressure at 40°C to remove most of the dichloromethane and tetrahydrofuran, yielding a viscous crude product. The crude product was transferred to a distillation flask and distilled under reduced pressure at a vacuum of 100 Pa. The fraction corresponding to the boiling range of the product was collected to obtain the final product as shown in Formula 3, which is denoted as Sample 3.

[0048] Example 4 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 4 were prepared using N,N'-carbonyldiimidazole and 2,2-difluoroethanol. The specific process was the same as in Example 1, except that the activation temperature in step S1 was 0°C and the catalytic activation time was 40 min. The subsequent process was the same as in Example 1, and the final product as shown in Formula 4 was obtained, which is denoted as Sample 4.

[0049] Formula 4 Example 5 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 5 were prepared using N,N'-carbonyldiimidazole and ethanol. The specific process was the same as in Example 1, and the product was designated as Sample 5.

[0050] Formula 5 Example 6 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 6 were prepared using N,N'-carbonyldiimidazole and isopropanol. The specific process was the same as in Example 1, except that the reaction temperature in step S3 was 10°C and the reaction time was 4 hours. The subsequent process was the same as in Example 1, and the final product as shown in Formula 6 was obtained, which is denoted as Sample 6.

[0051] Formula 6 Example 7 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 7 were prepared using N,N'-carbonyldiimidazole and hexanol. The specific process was the same as in Example 1, and it is referred to as Sample 7.

[0052] Formula 7 Example 8 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 8 were prepared using N,N'-carbonyldiimidazole and allyl alcohol. The specific process was the same as in Example 1, except that the reaction temperature in step S3 was -5°C, the reaction time remained unchanged, and the subsequent process was the same as in Example 1. The final product as shown in Formula 8 was obtained and denoted as Sample 8.

[0053] Formula 8 Example 9 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 9 were prepared using N,N'-carbonyldiimidazole and 2-chloroethanol. The specific process was the same as in Example 1, and the product was designated as Sample 9.

[0054] Formula 9 Example 10 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 10 were prepared using N,N'-carbonyldiimidazole and 3-phenyl-1-propanol. The specific process was the same as in Example 1, and the product was designated as Sample 10.

[0055] Formula 10 Example 11 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 11 were prepared using N,N'-carbonyldiimidazole and 2-methoxyethanol. The specific process was the same as in Example 1, and the product was referred to as Sample 11.

[0056] Formula 11 Example 12 In this embodiment, imidazole carboxylic acid ester products as shown in Formula 12 were prepared using N,N'-carbonyldiimidazole and 3-phenyl-2-propyn-1-ol. The specific process was the same as in Example 1, except that the dropping time in step S2 was 60 min; the reaction temperature in step S3 was -5℃, and the reaction time remained unchanged. The subsequent process was the same as in Example 1, and the final product as shown in Formula 12 was obtained, which was denoted as Sample 12.

[0057] Formula 12 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, the addition of N-methylimidazole is omitted, and only a mixed solvent of dichloromethane and tetrahydrofuran is used for catalytic activation. The subsequent process is the same as in Example 1, and the final product shown in Formula 3 is prepared, which is referred to as control 1.

[0058] 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, triethylamine is used in place of N-methylimidazole for catalytic activation in an equal amount, and the subsequent process is the same as in Example 1, to prepare the final product as shown in Formula 3, which is referred to as control 2.

[0059] 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 tetrahydrofuran is omitted in step S1, and 100 mL of dichloromethane is used instead of the mixed solvent of 95 mL of dichloromethane and 5 mL of tetrahydrofuran. The subsequent process is the same as in Example 1, and the final product shown in Formula 3 is prepared, which is referred to as control product 3.

[0060] Comparative Example 4 This comparative example provides a comparative preparation method, the specific implementation of which is the same as that of Example 1, except that: the catalytic activation process in step S1 is omitted, and equal amounts of N,N'-carbonyldiimidazole and N-methylimidazole are added to the mixed solvent used in Example 1. After stirring at 300 r / min for 30 s, the subsequent process is carried out directly to prepare the final product shown in Formula 3, which is referred to as control product 4.

[0061] 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 S2, the dropping time of the dichloromethane solution containing the hydroxyl group is adjusted to control the dropping time to 15 min, and the subsequent process is the same as in Example 1, to prepare the final product as shown in Formula 3, which is denoted as control product 5.

[0062] Analysis and Testing Purity analysis of each sample or reference standard was performed using high-performance gas chromatography (HPLC), and the moisture content of the samples or reference standards was determined. Product yields were also calculated. The results are shown in Table 1. The HPLC chromatograms of samples 1, 4, and 5 are shown below. Figures 1-3 .

[0063] Product yield = Actual weight of the product obtained (g) / Theoretical yield (g) calculated using the starting material amount shown in Formula 1 × 100%.

[0064] In addition, structural confirmation was performed using a high-performance gas chromatography-mass spectrometry (HPLC-MS) system and nuclear magnetic resonance (NMR) analysis. The relevant test spectra for samples 1, 4, and 5 are shown in [reference needed]. Figures 4-9 .

[0065] Table 1: Summary Table of Product Yield and Quality Analysis As shown in Table 1, the present invention, using N-methylimidazole as a catalyst and combining a pre-activation step, a mixed solvent system, and a controlled dropping process, achieved a stable purity of 99.7% or higher for all product samples, with moisture content effectively controlled to ≤60 ppm and yields exceeding 86%. This demonstrates that the preparation method of the present invention exhibits excellent reaction selectivity and conversion efficiency. Combined with optimized post-treatment processes, it effectively removes impurities and trace amounts of moisture, enabling the products to meet the stringent purity requirements of high-end applications.

[0066] In Examples 1-3, which used cyclopropane-methanol as a substrate, the reaction parameters and material ratios were adjusted, but the purity, moisture content, and yield of the resulting products remained at excellent levels, demonstrating that the process of the present invention is stable and has good process controllability and reproducibility.

[0067] The products of Examples 4, 6, and 12 all had a purity of 99.7%, which is relatively low compared to other examples. The moisture content was also relatively high, which is directly related to the inherent characteristics of their substrates, namely, the substrates possessing strong electron-withdrawing effects, steric hindrance, or highly conjugated sensitive structures. Nevertheless, the catalytic and process system of this invention can successfully overcome the reaction difficulties caused by different substrates and produce high-purity products, demonstrating the strong adaptability of this invention to substrates with special structures.

[0068] The products from Examples 5 and 7-11 all achieved a purity of 99.8% or higher, with relatively lower moisture content and higher yields. This indicates that this method is more effective at catalytic conversion of conventional primary alcohols without special steric hindrance or electronic effects, as well as alcohols containing halogens, electron-donating ether bonds, or indirect aryl groups, achieving near-quantitative high-purity conversion and demonstrating the high versatility and efficiency of this invention.

[0069] It is particularly noteworthy that for allyl alcohol (Example 8) and 3-phenyl-2-propyn-1-ol (Example 12) containing unsaturated bonds that require protection, the purity of the product is still as high as 99.7% or above under the low-temperature controlled process of the present invention. This proves that while achieving efficient conversion, the method has excellent compatibility and protection capabilities for sensitive functional groups such as olefins and alkynes, further expanding its application scope.

[0070] In contrast, reference standard 1, which completely omitted the N-methylimidazole catalyst, not only showed a significant decrease in product purity and yield but also a severely high moisture content. This demonstrates that N-methylimidazole is indispensable as a core reaction catalyst; its absence leads to insufficient reaction kinetics, low conversion rate, and increased side reactions.

[0071] Reference standard 2, using triethylamine, a conventional organic base, instead of N-methylimidazole, yielded acceptable purity and yield, but failed to meet the high purity requirement due to its high moisture content. This indicates that while triethylamine provides some catalytic activity, its strongly alkaline environment exacerbates the hydrolysis side reactions, making it impossible to achieve both high purity and low moisture residue. More importantly, the N-methylimidazole used in this invention has a highly similar structure to the imidazole byproduct inherent in the reaction. Its mechanism of action also includes reversible competitive binding with the active intermediate, thereby inhibiting the formation pathway of the free imidazole byproduct. This is a catalytic characteristic that triethylamine, as a base catalyst, lacks.

[0072] Reference standard 3, prepared using pure dichloromethane as both the catalyst and reaction system, exhibited decreased product purity and a significantly increased water content. This demonstrates that tetrahydrofuran, as a co-solvent, is crucial for forming a homogeneous and efficient pre-activated system; its absence affects the stability and reaction selectivity of the catalytic intermediate and weakens the system's dehydration capacity.

[0073] Reference standard 4 omitted the pre-activation step, resulting in a comprehensive decrease in product purity, moisture content, and yield. This indicates that the pre-activation step is a crucial process to ensure that N,N'-carbonyldiimidazole and N-methylimidazole fully react to form a highly active catalytic intermediate. Omitting this step will lead to an increase in byproducts.

[0074] In the preparation of reference standard 5, the dropping time was shortened to 15 minutes. This resulted in the lowest purity, highest moisture content, and lowest yield among all reference standards used. This demonstrates that controlled, slow dropping is a key process control point for maintaining a low-temperature reaction environment and avoiding localized overheating and the outbreak of side reactions.

[0075] In summary, the N-methylimidazolium catalyst, pre-activation step, mixed solvent system, and controlled dropping process employed in this invention constitute a synergistic and indispensable overall technical solution. This invention successfully overcomes the limitations of existing methods in terms of efficiency, selectivity, and purity control, providing a reliable technical route for the high-purity, low-moisture, and high-yield synthesis of imidazolium carboxylic acid esters.

[0076] 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 imidazole carboxylic acid ester, characterized in that, N,N'-carbonyldiimidazole was reacted with the compound containing a hydroxyl group shown in Formula 1 under the catalysis of N-methylimidazole. The reaction temperature and reaction time were controlled to obtain the imidazole carboxylic acid ester compound shown in Formula 2. Wherein, R is selected from alkyl groups with 1 to 10 substituted or unsubstituted carbon atoms, alkenyl groups with 2 to 10 substituted or unsubstituted carbon atoms, and alkynyl groups with 2 to 10 substituted or unsubstituted carbon atoms; The substituent is at least one selected from ether, cyano, nitro, halogen, and aromatic ring. Formula 1; Equation 2.

2. The preparation method according to claim 1, characterized in that, R is selected from alkyl groups with 1 to 6 substituted or unsubstituted carbon atoms, alkenyl groups with 2 to 6 substituted or unsubstituted carbon atoms, and alkynyl groups with 2 to 6 substituted or unsubstituted carbon atoms; the substituted substituent is at least one of fluorine, chlorine, bromine, iodine, and phenyl.

3. The preparation method according to claim 1, characterized in that, The molar ratio of the hydroxyl-containing compound, N,N'-carbonyldiimidazole, and N-methylimidazole is 1:(1.02–1.20):(0.015–0.025).

4. The preparation method according to claim 1, characterized in that, The reaction temperature is -5℃ to 10℃, and the reaction time is 2h to 4h.

5. The preparation method according to claim 1, characterized in that, The reaction requires prior catalytic activation of N,N'-carbonyldiimidazole and N-methylimidazole in a mixed reaction solvent before adding a hydroxyl-containing compound to carry out the reaction.

6. The preparation method according to claim 5, characterized in that, The mixed reaction solvent is a mixture of dichloromethane and tetrahydrofuran in a volume ratio of (90-100):

5.

7. The preparation method according to any one of claims 5 or 6, characterized in that, The amount of mixed solvent used is 95 mL to 105 mL for each mole of compound containing hydroxyl groups.

8. The preparation method according to claim 5, characterized in that, The catalytic activation is carried out at a temperature of -10℃ to 0℃ for a time of 20 min to 40 min.

9. The preparation method according to claim 5, characterized in that, The compound containing hydroxyl groups is added as follows: the compound containing hydroxyl groups is added to dichloromethane at a ratio of 1 mol:(50 mL to 100 mL) to prepare a dichloromethane solution containing the compound containing hydroxyl groups, and the dichloromethane solution containing the compound containing hydroxyl groups is added dropwise to the mixed reaction solvent.

10. The preparation method according to claim 9, characterized in that, The dropping time of the dichloromethane solution containing hydroxyl groups should be controlled between 30 and 60 minutes.

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