A continuous flow process for the synthesis of 4-hydroxycyclohexyl methacrylate

Abstract

The application provides a continuous flow synthesis process of 4-hydroxycyclohexyl methacrylate, which comprises the following steps: mixing 1,4-cyclohexanediol with water to prepare a solution as material A; dissolving methacrylic acid in a water-immiscible organic solvent to prepare an organic solution as material B; synchronously and continuously feeding the material A and the material B into a continuous flow reactor filled with a solid acid catalyst, so that two phases form a phase interface in the catalyst bed of the continuous flow reactor, and the reaction is carried out in the water phase of the material A; the 4-hydroxycyclohexyl methacrylate generated in the reaction is quickly distributed into the organic phase of the material B at the phase interface, continuously flows out of the continuous flow reactor with the organic phase, and the reaction liquid flowing out of the reactor is collected; and the organic phase containing the 4-hydroxycyclohexyl methacrylate is collected after phase separation. In the process, the 4-hydroxycyclohexyl methacrylate generated in the esterification reaction can be immediately extracted into the organic phase, and secondary esterification with methacrylic acid to generate a double ester impurity can be avoided.

Description

Technical Field

[0001] This invention relates to the field of organic synthesis, and in particular to a continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate. Background Technology

[0002] 4-Hydroxycyclohexyl methacrylate (HCHMA) is a functional acrylate monomer that combines high reactivity with excellent material properties. Its molecular structure contains carbon-carbon double bonds that can be polymerized by free radicals, active secondary hydroxyl groups, and a rigid cyclohexane skeleton. It is widely used as a crosslinking agent, polymerization monomer, and auxiliary agent. It is a core raw material in the fields of photocurable coatings, adhesives, and high-performance polymers, and its application value is outstanding.

[0003] Currently, the main synthetic route for 4-hydroxycyclohexyl methacrylate is direct esterification, supplemented by transesterification. Direct esterification, using 1,4-cyclohexanediol and methacrylic acid as raw materials, is the mainstream industrial route due to readily available raw materials and a simple process. However, it suffers from key bottlenecks such as uncontrollable side reactions, low product purity, and high purification costs. Transesterification, using 1,4-cyclohexanediol and methyl methacrylate as raw materials, offers relatively mild reaction conditions, but suffers from low equilibrium conversion rates, difficulty in catalyst recovery, and difficulty in removing product residues, severely limiting its industrial application.

[0004] The existing process suffers from three major insurmountable technical defects: First, the diester side reaction cannot be suppressed at the source, which is the most critical pain point. 1,4-Cyclohexanediol contains two symmetrical active hydroxyl groups. In traditional esterification systems, the raw materials, catalysts, and products are in the same phase. The resulting target 4-hydroxycyclohexyl methacrylate monoester product will continue to undergo secondary esterification with methacrylic acid, generating 1,4-cyclohexanediol dimethacrylate diester impurities. This impurity not only significantly reduces product yield and selectivity but also causes premature cross-linking and gelation of the subsequent polymerization system. Furthermore, its physicochemical properties are highly similar to the target product, making it difficult to completely separate using conventional purification methods. Second, side reactions are frequent, resulting in poor product quality stability. In traditional single-phase organic reaction systems, the materials are exposed to high temperatures for extended periods. In addition to the diester side reaction, it is highly susceptible to side reactions such as methacrylic acid self-polymerization, raw material carbonization, and etherification. The product has high color and complex impurity composition, requiring additional purification steps such as decolorization and multiple alkali and water washing, significantly extending the production cycle and exacerbating the risk of product quality fluctuations. Furthermore, to promote the forward reaction, existing processes typically employ excessive feeding of methacrylic acid, further exacerbating various side reactions and creating a vicious cycle. Thirdly, the processes are energy-intensive and environmentally challenging, making continuous green production difficult. Existing technologies generally employ a batch process of "full-scale reaction followed by centralized purification," which cannot separate the target product in real-time during the reaction, leading to continuous side reactions and a significant increase in post-processing load. The removal of excess acid, catalyst, and impurities requires large amounts of alkali for neutralization, generating large quantities of high-salt organic wastewater, resulting in high environmental treatment costs. The high-vacuum distillation step is energy-intensive and carries safety risks associated with high-temperature polymerization of materials, making it difficult to meet the demands of continuous and green industrial production.

[0005] Therefore, developing a green and efficient method for preparing 4-hydroxycyclohexyl methacrylate that can suppress the formation of diester impurities at the source of the reaction has become a technical challenge that urgently needs to be solved in this field. Summary of the Invention

[0006] The purpose of this invention is to provide a continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate. The continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate provided by this invention can suppress the formation of diester impurities at the source of the reaction, resulting in high product yield and purity, and is green and efficient, possessing significant industrial application value and good economic benefits.

[0007] To achieve the above-mentioned objectives, the present invention provides the following technical solution:

[0008] This invention provides a continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate, characterized by comprising the following steps:

[0009] (1) Mix 1,4-cyclohexanediol with water to prepare an aqueous solution, which is used as material A;

[0010] (2) Dissolve methacrylic acid in an organic solvent that is immiscible with water to prepare an organic solution, which is used as material B;

[0011] (3) Material A and material B are simultaneously and continuously fed into a continuous flow reactor filled with solid acid catalyst, so that the two phases form a phase interface in the catalyst bed of the continuous flow reactor, and the esterification reaction is carried out in the aqueous phase of material A; the 4-hydroxycyclohexyl methacrylate generated by the reaction is rapidly distributed into the organic phase of material B at the phase interface and flows out of the continuous flow reactor with the organic phase.

[0012] (4) Collect the reaction liquid flowing out of the continuous flow reactor, and collect the organic phase containing 4-hydroxycyclohexyl methacrylate after phase separation.

[0013] Preferably, the mass fraction of 1,4-cyclohexanediol in material A in step (1) is 8%~20%; and the mass fraction of methacrylic acid in material B in step (2) is 8%~20%.

[0014] Preferably, the mass fraction of 1,4-cyclohexanediol in material A in step (1) is 8%~12%.

[0015] Preferably, the mass fraction of methacrylic acid in material B in step (2) is 8%~15%.

[0016] Preferably, in step (2), the organic solvent is selected from one or more of toluene, xylene, chlorobenzene, nitrobenzene, methyl isobutyl ketone, 1,2-dichloroethane and isopropyl ether.

[0017] Preferably, in step (3), the volumetric flow rate ratio of material A to material B entering the continuous flow reactor is 3:1 to 6:1.

[0018] Preferably, in step (3), the solid acid catalyst is selected from one or more of acidic cation exchange resin, β zeolite, silica-alumina molecular sieve and γ-alumina.

[0019] Preferably, in step (3), the reaction temperature of the esterification reaction is 70~100℃; the residence time of material A and material B in the continuous flow reactor is 1~10min.

[0020] Preferably, step (4) further includes detecting the 1,4-cyclohexanediol content in the aqueous phase obtained by phase separation, adding 1,4-cyclohexanediol to a mass fraction of 8-20% based on the detection results to obtain a recovered liquid, which can be directly used in the next batch of material A preparation process or directly fed into a continuous flow reactor as feed to participate in the reaction.

[0021] Preferably, step (4) further includes adding a polymerization inhibitor to the organic phase after the organic phase is separated; the polymerization inhibitor is selected from one or more of hydroquinone, p-hydroxyanisole, 2,2,6,6-tetramethylpiperidine-1-oxy radical and phenothiazine.

[0022] Technical effect

[0023] This invention provides a continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate, comprising the following steps: mixing 1,4-cyclohexanediol with water to prepare an aqueous solution, designated as material A; dissolving methacrylic acid in an organic solvent immiscible with water to prepare an organic solution, designated as material B; passing material A and material B into a continuous flow reactor packed with a solid acid catalyst for esterification reaction. During this process, the solid acid catalyst is preferentially wetted by the aqueous phase of material A, and its acid catalytic active center is confined to the catalyst surface wetted by the aqueous phase of material A and the phase interface between material A and material B. Therefore, the 4-hydroxycyclohexyl methacrylate generated in the reaction is immediately extracted into the organic phase through the phase interface, escaping the acid catalytic active center, thus avoiding secondary esterification with methacrylic acid to form diester impurities; finally, collecting the reaction liquid flowing out of the continuous flow reactor, collecting the organic phase after phase separation, and separating 4-hydroxycyclohexyl methacrylate from the organic phase. This invention can effectively control the formation of diesters during the reaction process. Furthermore, the raw material 1,4-cyclohexanediol in the aqueous phase can be recycled and reused. The overall technical solution of this invention has high industrial application value and can generate good economic benefits. Attached Figure Description

[0024] Figure 1 The HPLC chromatogram of 4-hydroxycyclohexyl methacrylate prepared in Example 1 of the present invention is shown below.

[0025] Figure 2 The HPLC chromatogram of 4-hydroxycyclohexyl methacrylate prepared in Example 2 of the present invention;

[0026] Figure 3 The 4-hydroxycyclohexyl methacrylate prepared in Example 2 of this invention 1 H NMR spectrum. Detailed Implementation

[0027] This invention provides a continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate, characterized by comprising the following steps:

[0028] (1) Mix 1,4-cyclohexanediol with water to prepare an aqueous solution as material A; (2) Dissolve methacrylic acid in an organic solvent that is immiscible with water to prepare an organic solution as material B; (3) Simultaneously and continuously feed material A and material B into a continuous flow reactor packed with a solid acid catalyst, so that the two phases form a phase interface in the catalyst bed of the continuous flow reactor, and the esterification reaction is carried out in the aqueous phase of material A; the 4-hydroxycyclohexyl methacrylate generated by the reaction is rapidly distributed into the organic phase of material B at the phase interface and flows out of the continuous flow reactor continuously with the organic phase; (4) Collect the reaction liquid flowing out of the continuous flow reactor, and collect the organic phase containing 4-hydroxycyclohexyl methacrylate after phase separation. In this invention, the solid acid catalyst is preferentially wetted by the aqueous phase of material A, and its acid catalytic active center is confined to the catalyst surface wetted by material A and the phase interface between material A and material B; the 4-hydroxycyclohexyl methacrylate generated by the reaction is immediately extracted into the organic phase through the phase interface and removed from the acid catalytic active center, thereby avoiding secondary esterification with methacrylic acid to generate diester impurities.

[0029] In step (1) of the present invention, the mass fraction of 1,4-cyclohexanediol in material A is preferably 8% to 20%, more preferably 8% to 12%; in step (2) of the present invention, the mass fraction of methacrylic acid in material B is preferably 8% to 20%, more preferably 8% to 15%.

[0030] In step (1) of this invention, the mass fraction of 1,4-cyclohexanediol in material A is preferably 8% to 12%.

[0031] In step (2) of the present invention, the mass fraction of methacrylic acid in material B is preferably 8% to 15%.

[0032] In step (2) of the present invention, the organic solvent is preferably 4-hydroxycyclohexyl methacrylate with a higher solubility in water and does not react chemically with the reactants or products.

[0033] In step (2) of the present invention, the organic solvent is preferably selected from one or more of toluene, xylene, methylcyclohexane, n-heptane, cyclohexane, chlorobenzene, nitrobenzene, methyl isobutyl ketone, 1,2-dichloroethane and isopropyl ether, and more preferably selected from one or more of toluene, xylene and methylcyclohexane.

[0034] In step (3) of the present invention, the volumetric flow rate ratio of material A to material B entering the continuous flow reactor is preferably 3:1 to 6:1, more preferably 3:1 to 4:1.

[0035] In step (3) of the present invention, the total volumetric flow rate of material A and material B is preferably 40-80 mL / min, more preferably 40-65 mL / min.

[0036] In step (3) of the present invention, the continuous flow reactor is preferably a fixed bed continuous flow reactor, a microchannel continuous flow reactor or a tower continuous flow reactor, and more preferably a fixed bed continuous flow reactor.

[0037] In step (3) of the present invention, the solid acid catalyst is preferably a hydrophilic solid acid catalyst, more preferably selected from one or more of acidic cation exchange resin, β zeolite, silica-alumina molecular sieve and γ-alumina.

[0038] In this invention, the strongly acidic cation exchange resin is preferably a styrene-based macroporous strongly acidic cation exchange resin with sulfonic acid functionalization, and its degree of crosslinking is preferably 1% to 10%, more preferably 3% to 8%; its particle size is preferably 0.3 to 1.2 mm.

[0039] In this invention, the strong acid cation exchange resin is preferably selected from one or more of the following: D001 type macroporous strong acid styrene-based cation exchange resin, NKC-9 type dry hydrogen catalytic resin, Amberlyst 15 resin, and Amberlyst 35 resin.

[0040] In this invention, the SiO2 / Al2O3 molar ratio of the hydrogen-form β-zeolite is preferably 10 to 100, more preferably 20 to 50.

[0041] In this invention, the hydrogen-form silica-alumina molecular sieve is preferably selected from one or more of hydrogen-form Y-type molecular sieve, hydrogen-form mordenite zeolite, and hydrogen-form ZSM-5 molecular sieve, and more preferably from hydrogen-form Y-type molecular sieve. In this invention, the SiO2 / Al2O3 molar ratio of the hydrogen-form Y-type molecular sieve is preferably 3 to 30.

[0042] In step (3) of the present invention, the reaction temperature of the esterification reaction is preferably 70~100℃, more preferably 70~80℃.

[0043] In step (3) of the present invention, the reaction residence time of material A and material B in the continuous flow reactor is preferably 1 to 10 min, more preferably 1 to 8 min.

[0044] In this invention, step (4) further includes quantitatively detecting the 1,4-cyclohexanediol content in the aqueous phase obtained by phase separation, adding 1,4-cyclohexanediol to a mass fraction of 8-20% based on the detection results, obtaining a recovered liquid, which is directly used in the next batch of material A preparation process, or directly fed into a continuous flow reactor as feed to participate in the reaction.

[0045] In this invention, step (4) further includes adding a polymerization inhibitor to the organic phase after separation; the polymerization inhibitor is selected from one or more of hydroquinone, p-hydroxyanisole, 2,2,6,6-tetramethylpiperidine-1-oxy radical and phenothiazine.

[0046] In this invention, step (4) further includes using a receiving tank to continuously collect the reaction liquid flowing out of the continuous flow reactor, cooling and stratifying it, collecting the organic phase, adding a polymerization inhibitor to the organic phase, and then washing, concentrating and distilling the organic phase to obtain 4-hydroxycyclohexyl methacrylate.

[0047] In this invention, the volume of water used for washing is preferably 2 to 3 times the volume of the reaction liquid. The number of washes is preferably 2 to 3. Through this washing process, the present invention can remove residual polymerization inhibitors and water-soluble impurities from the reaction liquid.

[0048] This invention does not have special requirements for the concentration method; any concentration method well known to those skilled in the art can be used. In this invention, the concentration is preferably to 20-30% of the original volume.

[0049] To further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0050] Example 1

[0051] Add 400.0 g (3.44 mol) of 1,4-cyclohexanediol and 3.9 L of deionized water to a 5 L single-necked flask, and stir at room temperature until completely dissolved to obtain material A. Add 100.0 g (1.16 mol) of methacrylic acid and 0.9 kg of toluene to a 2 L single-necked flask, and stir at room temperature until completely dissolved to obtain material B. A fixed-bed reactor is filled with hydrogen-form β-zeolite catalyst (Si / Al = 25-55). The reactor is heated to 70-80 °C and kept at a stable temperature. Start the dual metering pumps and simultaneously and continuously feed material A and material B into the fixed-bed continuous flow reactor at a volumetric flow rate ratio of 4:1. Control the total feed rate of material A and material B at 40 mL / min. The materials flow through the catalyst bed to complete the esterification reaction. The reaction liquid at the reactor outlet continuously flows into the receiving tank, and the temperature of the liquid in the receiving tank is controlled at 20-30 °C throughout the process. After all materials A and B have been fed, the metering pump is stopped, all reaction liquid in the receiving tank is collected, and the mixture is allowed to stand and separate. The polymerization inhibitor p-tert-butylcatechol is added to the upper organic phase, and after washing with water, concentration under reduced pressure, and high-temperature distillation, 196.8 g of 4-hydroxycyclohexyl methacrylate is obtained, with a gas chromatographic purity of 98.38% and a molar yield of 91.96%. The content of 1,4-cyclohexanediol in the lower aqueous phase obtained by separation is quantitatively detected, and the recovered liquid is reused in the preparation process of the next batch of material A.

[0052] Example 2

[0053] 1,4-cyclohexanediol (200.0 g, 1.72 mol) and deionized water (3.9 L) were added to a 3 L single-necked flask and stirred at room temperature until completely dissolved to obtain material A. Methacrylic acid (50.0 g, 0.58 mol) and toluene (450 g) were added to a 2 L single-necked flask and stirred at room temperature until completely dissolved to obtain material B. A fixed-bed reactor was filled with γ-alumina catalyst, and the reactor was heated to 95 °C and kept at a stable temperature. Dual metering pumps were turned on, and material A and material B were simultaneously and continuously fed into the fixed-bed continuous flow reactor at a volumetric flow rate ratio of 3:1. The total feed rate of material A and material B was controlled at 65 mL / min. The materials flowed through the catalyst bed to complete the esterification reaction. The reaction liquid at the reactor outlet continuously flowed into a receiving tank, and the temperature of the liquid in the receiving tank was controlled at 20-30 °C throughout the process. After all materials A and B have been fed, the metering pump is stopped, all reaction liquid in the receiving tank is collected, and the mixture is allowed to stand and separate. The polymerization inhibitor phenothiazine is added to the upper organic phase, and after washing with water, vacuum concentration, and high-temperature distillation, 101.9 g of 4-hydroxycyclohexyl methacrylate is obtained with a gas chromatographic purity of 99.72% and a molar yield of 95.32%. The 1,4-cyclohexanediol content of the lower aqueous phase obtained by separation is quantitatively detected. Based on the detection results, 1,4-cyclohexanediol is added to bring the mass fraction to 10%. The obtained recovered liquid is directly fed into the continuous flow reactor as feed to participate in the reaction.

[0054] Comparative Example 1

[0055] Add 400.0 g (3.44 mol) of 1,4-cyclohexanediol, 100.0 g (1.16 mol) of methacrylic acid, and 4.8 L of deionized water to a 5 L single-necked flask. Stir at room temperature until completely dissolved to obtain a homogeneous aqueous feed material, which is then set aside. A fixed-bed reactor is loaded with a hydrogen-form β-zeolite catalyst (Si / Al = 25-55). The reactor is heated to 70-80 °C and kept at a stable temperature. The metering pump is turned on, and the homogeneous feed material is continuously fed into the fixed-bed continuous flow reactor at a total feed flow rate of 40 mL / min. The material flows through the catalyst bed to complete the esterification reaction. The reaction liquid at the reactor outlet continuously flows into the receiving tank, and the temperature of the liquid in the receiving tank is controlled at 20-30 °C throughout the process. After all materials have been fed, the metering pump is stopped, and all the reaction liquid in the receiving tank is collected. Toluene (0.9 kg) is added to the reaction liquid, and the mixture is stirred and extracted at room temperature for 30 min. The mixture is then allowed to stand and separate. The polymerization inhibitor p-tert-butylcatechol is added to the upper organic phase, and then the mixture is washed with water, concentrated under reduced pressure, and distilled at high temperature to obtain 150.6 g of 4-hydroxycyclohexyl methacrylate, with a gas chromatographic purity of 91.8% and a molar yield of 70.3%. Gas chromatographic analysis shows that the content of diester impurity (1,4-cyclohexanediol dimethacrylate) in the reaction liquid is 4.7%.

[0056] This invention provides a continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate. The process involves simultaneously and continuously feeding a prepared aqueous solution of 1,4-cyclohexanediol and an organic solution of methacrylic acid into a continuous flow reactor packed with a hydrophilic solid acid catalyst for esterification. During this process, the solid acid catalyst is preferentially wetted by the aqueous phase containing 1,4-cyclohexanediol. Its acid catalytic active sites are confined to the surface of the catalyst wetted by the aqueous phase and at the interface between the aqueous and organic phases. Since the aqueous and organic phases are constantly flowing, the 4-hydroxycyclohexyl methacrylate generated in the reaction can be extracted into the organic phase through the interface, escaping the acid catalytic active sites and avoiding secondary esterification with methacrylic acid. This effectively controls the formation of diester impurities in the reaction. Furthermore, the continuous flow reactor ensures the reaction liquid remains in a flowing state, increasing the material contact area and improving reactant conversion and product selectivity. Additionally, the 1,4-cyclohexanediol in the aqueous phase can be recycled. Overall, this invention has high industrial application value and can generate good economic benefits.

[0057] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate, characterized in that, Includes the following steps: (1) Mix 1,4-cyclohexanediol with water to prepare an aqueous solution, which is used as material A; (2) Dissolve methacrylic acid in an organic solvent that is immiscible with water to prepare an organic solution, which is used as material B; (3) Material A and material B are simultaneously and continuously fed into a continuous flow reactor filled with a solid acid catalyst, so that the two phases form a phase interface in the catalyst bed of the continuous flow reactor, and the esterification reaction is carried out in the aqueous phase of material A; the 4-hydroxycyclohexyl methacrylate generated by the reaction is rapidly distributed into the organic phase of material B at the phase interface and flows out of the continuous flow reactor with the organic phase. (4) Collect the reaction liquid flowing out of the continuous flow reactor, and collect the organic phase containing 4-hydroxycyclohexyl methacrylate after phase separation.

2. The continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate according to claim 1, characterized in that, In step (1), the mass fraction of 1,4-cyclohexanediol in material A is 8%~20%; in step (2), the mass fraction of methacrylic acid in material B is 8%~20%.

3. The continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate according to claim 2, characterized in that, In step (1), the mass fraction of 1,4-cyclohexanediol in material A is 8%~12%.

4. The continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate according to claim 2, characterized in that, In step (2), the mass fraction of methacrylic acid in material B is 8%~15%.

5. The continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate according to claim 1, characterized in that, In step (2), the organic solvent is selected from one or more of toluene, xylene, chlorobenzene, nitrobenzene, methyl isobutyl ketone, 1,2-dichloroethane and isopropyl ether.

6. The continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate according to claim 1, characterized in that, The volumetric flow rate ratio of material A to material B entering the continuous flow reactor is 3:1 to 6:

1.

7. The continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate according to claim 1, characterized in that, In step (3), the solid acid catalyst is selected from one or more of acidic cation exchange resin, β zeolite, silica-alumina molecular sieve and γ-alumina.

8. The continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate according to claim 1, characterized in that, In step (3), the reaction temperature of the esterification reaction is 70~100℃, and the reaction residence time of material A and material B in the continuous flow reactor is 1~10min.

9. The continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate according to claim 2, characterized in that, Step (4) further includes: detecting the 1,4-cyclohexanediol content in the aqueous phase obtained by phase separation, adding 1,4-cyclohexanediol to a mass fraction of 8-20% based on the detection results, and obtaining a recovered liquid. The recovered liquid is directly used in the next batch of material A preparation process, or directly fed into the continuous flow reactor as feed to participate in the reaction.

10. The continuous flow synthesis process for 4-hydroxycyclohexyl methacrylate according to claim 1, characterized in that, Step (4) further includes adding a polymerization inhibitor to the organic phase after the organic phase is separated; the polymerization inhibitor is selected from one or more of hydroquinone, p-hydroxyanisole, 2,2,6,6-tetramethylpiperidine-1-oxy radical and phenothiazine.

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