A method for synthesizing oxetane derivatives using a microreactor

Abstract

The present invention provides a method for synthesizing oxetane derivatives in a microreactor, which comprises reacting 3-ethyl-3-hydroxymethyloxetane with a compound of the general formula R-(X): n The process includes the steps of transporting a raw material Ha (represented by the formula: Ha (where X is a halogen element), a catalyst, and an alkali into a microreactor to carry out an etherification reaction to obtain an etherified product system, and separating the etherified product system to obtain an oxetane derivative. The use of a microreactor significantly improves the mass transfer and heat conductivity of the reaction system, shortens the reaction time, improves production efficiency, increases product yield, enables the process to be continuous and automated, and improves process safety. At the same time, the volume of the reaction equipment required for the synthesis process is small, occupies a small area at the production base, and is highly safe.

Description

[Technical field]

[0001] The present invention relates to the field of organic synthesis, and more particularly to a method for synthesizing an oxetane derivative using a microreactor. [Background technology]

[0002] Using 3-ethyl-3-hydroxymethyloxetane as a raw material, a series of oxetane derivatives can be obtained by etherification reaction with halogenated organic compounds under the action of alkali, and used as a monomer in photocurable cationic systems, and can be applied in the fields of photocurable inks, paints, adhesives, etc. Representative products include 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane, bis[1-ethyl(3-oxetanyl)methyl]ether, and 3-benzyloxymethyl-3-ethyloxetane. These oxetane products have low viscosity, good dilution properties, fast crosslinking speed, and excellent performance after film formation, making them one of the raw materials with the greatest market potential in the cationic photocuring field.

[0003] Taking 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane as an example, its industrial production is obtained by etherifying 3-ethyl-3-hydroxymethyloxetane and epichlorohydrin as raw materials with the action of solid sodium hydroxide. Since the reaction system is a liquid-solid heterogeneous phase, mass transfer is difficult. In order to ensure the conversion rate, epichlorohydrin and sodium hydroxide must be in excess of 50% or more. 3 The reaction process is carried out in a reactor, and the reaction time is approximately 12 hours. The post-processing steps of filtration, rectification, etc. take approximately 30 hours. The production process requires the complicated operation of adding solid sodium hydroxide in several batches, which poses potential safety issues such as temperature runaway.

[0004] In view of the above problems, it is necessary to provide a method for synthesizing oxetane derivatives which has a short reaction time, high mass transfer efficiency, and good safety. Summary of the Invention

[0005] The main objective of the present invention is to provide a method for synthesizing oxetane derivatives using a microreactor, which solves the problems of long reaction time, complicated operation and poor safety in the conventional methods for synthesizing oxetane derivatives, and ensures the selectivity of the etherification reaction and improves the product yield while realizing continuous production.

[0006] To achieve the above object, the present invention provides a method for synthesizing an oxetane derivative in a microreactor, the oxetane derivative having a structure represented by formula (I).

[0007] [ka] [Wherein, R is C2 to C 12 a straight-chain or branched-chain alkyl group, an alkyl group containing an oxirane structure, an alkyl group containing an oxetane structure, a phenyl group, a tolyl group, a benzyl group, or a biphenyl group. n is 1 to 4.]

[0008] The synthesis method for synthesizing the above oxetane derivatives in a microreactor is to synthesize 3-ethyl-3-hydroxymethyloxetane and a compound represented by the general formula R-(X): n The method includes a step of transporting a raw material Ha represented by the formula (X is a halogen element), a catalyst, and an alkali into a microreactor to carry out an etherification reaction to obtain an etherification product system, and a step of separating the etherification product system to obtain an oxetane derivative.

[0009] Furthermore, the inner diameter of the reaction channel of the microreactor is 200 to 10,000 μm.

[0010] Furthermore, the alkali is an alkali metal compound or an aqueous solution of an alkali metal compound, and the alkali metal compound is one or more selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, and calcium hydroxide. Preferably, the alkali metal compound is sodium hydroxide. The concentration of the aqueous solution of the alkali metal compound is 10% to 20%. The catalyst is one or more selected from the group consisting of polyethers, cyclic polyethers, and quaternary ammonium salts.

[0011] Further, the catalyst is one or more selected from the group consisting of polyethylene glycol, polyethylene glycol alkyl ether, 18-crown-6, 15-crown-5, tetraethylammonium bromide, tetrabutylammonium bromide, tetrabutylammonium chloride, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, and tetradecyltrimethylammonium chloride.

[0012] Furthermore, the catalyst is one or more selected from the group consisting of polyethylene glycol dimethyl ether, 18-crown-6, and tetrabutylammonium bromide.

[0013] Furthermore, the amount of catalyst added is 0.1 to 5% by weight based on the weight of 3-ethyl-3-hydroxymethyloxetane.

[0014] Furthermore, the amount of catalyst added is 0.5 to 2% by weight based on the weight of 3-ethyl-3-hydroxymethyloxetane.

[0015] Furthermore, the reaction temperature of the etherification reaction is 10 to 60° C., and the matter residence time is 2 to 5 minutes.

[0016] Furthermore, the apparatus employed in the separation process is a two-stage thin film evaporator or a fractionator.

[0017] Furthermore, the inner diameter of the reaction channel of the microreactor is 500 to 8000 μm.

[0018] By adopting the technical solution of the present invention, compared with ordinary reactors, the microreactor has the advantages of high heat transfer coefficient and mass transfer coefficient, good mixing performance, easy temperature control, safe and controllable process, etc. By utilizing the advantages of the microreactor to produce oxetane derivatives, the mass transfer and heat transfer properties of the reaction system can be greatly improved, the reaction time can be reduced to improve production efficiency, the product yield can be improved, the process can be continuous and automated, and the safety of the process can be improved. Limiting the pore size of the reaction channel of the microreactor within the above range is favorable to improving the selectivity of the etherification reaction, and thus the conversion rate of the oxetane derivatives. In addition, the volume of the reaction equipment required for the above synthesis process is small, the area occupied by the production base is small, the manpower required is small, and the safety is high. [Brief description of the drawings]

[0019] The drawings constituting a part of this application are provided for a further understanding of the present invention, and the exemplary embodiments of the present invention and the description thereof are used to interpret the present invention, and are not intended to unduly limit the present invention. [Figure 1] FIG. 1 shows a structural schematic diagram of an apparatus for producing an oxetane derivative according to an exemplary embodiment of the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0020] In addition, unless there is a contradiction, the embodiments and features in the embodiments in the present application may be combined with each other. The present invention will be described in detail below with reference to the embodiments.

[0021] As described in the Background Art, the conventional synthesis method of oxetane derivatives has problems such as long reaction time, complicated operation, and poor safety. In order to solve the above technical problems, the present application provides a synthesis method for synthesizing oxetane derivatives using a microreactor, and the oxetane derivative has a structure represented by formula (I).

[0022] [ka] [Wherein, R is C2 to C 12 a straight-chain or branched-chain alkyl group, an alkyl group containing an oxirane structure, an alkyl group containing an oxetane structure, a phenyl group, a tolyl group, a benzyl group, or a biphenyl group, and n is 1 to 4.]

[0023] The synthesis method of the oxetane derivative is to react 3-ethyl-3-hydroxymethyloxetane with a compound represented by the general formula R-(X) n The method includes a step of transporting a raw material Ha represented by the formula (X is a halogen element), a catalyst, and an alkali into a microreactor to carry out an etherification reaction to obtain an etherification product system, and a step of separating the etherification product system to obtain an oxetane derivative.

[0024] Compared with conventional reactors, microreactors have the advantages of high heat transfer coefficient and mass transfer coefficient, good mixing performance, easy temperature control, and safe and controllable process. By utilizing the advantages of microreactors to produce oxetane derivatives, it is possible to improve the mass transfer and heat conductivity of the reaction system, reduce the reaction time and improve production efficiency, improve the product yield, realize the continuation and automation of the process, and improve the safety of the process. In addition, the reaction equipment required for the above synthesis process is small in volume, occupies a small area of ​​the production base, requires few human resources, and is highly safe.

[0025] Preferably, the inner diameter of the reaction channel of the microreactor is 200 to 10,000 μm. Limiting the pore size of the reaction channel of the microreactor within the above range is advantageous for further improving the selectivity of the etherification reaction and further improving the conversion rate of the oxetane derivative. For example, the inner diameter of the reaction channel of the microreactor is 200 μm, 500 μm, 4,000 μm, 6,000 μm, 8,000 μm, or 10,000 μm, and more preferably, the inner diameter of the reaction channel of the microreactor is 500 to 8,000 μm.

[0026] In the above synthesis method, the alkali is an alkali metal compound or an aqueous solution of an alkali metal compound. The alkali metal compound may be any type commonly used in this field. Preferably, the alkali metal compound includes, but is not limited to, one or more selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, and calcium hydroxide. More preferably, the alkali metal compound is sodium hydroxide. The concentration of the aqueous solution of the alkali metal compound is 10 to 20%.

[0027] In the above synthesis method, the catalyst may be of a type commonly used in the art, and may include, but is not limited to, one or more selected from the group consisting of polyethers, cyclic polyethers, and quaternary ammonium salts. Preferably, the catalyst may include, but is not limited to, one or more selected from the group consisting of polyethylene glycol, polyethylene glycol alkyl ether, 18-crown-6, 15-crown-5, tetraethylammonium bromide, tetrabutylammonium bromide, tetrabutylammonium chloride, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, and tetradecyltrimethylammonium chloride. Compared with other catalysts, the use of such catalysts is advantageous in further improving the reaction rate of the etherification reaction and shortening the reaction period. More preferably, the catalyst may include, but is not limited to, one or more selected from the group consisting of polyethylene glycol dimethyl ether, 18-crown-6, and tetrabutylammonium bromide.

[0028] In one preferred embodiment, the catalyst is added in an amount of 0.1-5% by weight based on the weight of 3-ethyl-3-hydroxymethyloxetane. The amount of catalyst used includes, but is not limited to, the above range, and limiting it to the above range is advantageous for further improving the reaction rate of the etherification reaction. For example, the catalyst may be added in an amount of 0.1%, 0.5%, 1%, 1.5%, 2%, 3%, or 4% by weight based on the weight of 3-ethyl-3-hydroxymethyloxetane. More preferably, the catalyst is added in an amount of 0.5-2% by weight based on the weight of 3-ethyl-3-hydroxymethyloxetane.

[0029] In one preferred embodiment, the molar ratio of 3-ethyl-3-hydroxymethyloxetane to the halogen element in the raw material Ha is 1:(1.0-1.2). The molar ratio of 3-ethyl-3-hydroxymethyloxetane to the halogen element in the raw material Ha includes, but is not limited to, the above range, and limiting it to the above range is advantageous in improving the conversion rate of 3-ethyl-3-hydroxymethyloxetane.

[0030] In one preferred embodiment, the reaction temperature of the etherification reaction is 10 to 60°C, and the matter residence time is 2 to 5 min. The reaction temperature and matter residence time of the etherification reaction include, but are not limited to, the above ranges, and by limiting them to the above ranges, it is advantageous to further improve the yield of the etherification product. For example, the reaction temperature of the etherification reaction may be 10°C, 20°C, 30°C, 40°C, 50°C, or 60°C.

[0031] The above separation step can be carried out using equipment commonly used in the art. Preferably, the equipment employed in the separation step includes a two-stage thin film evaporator or a fractionator. EXAMPLES

[0032] Hereinafter, the present application will be described in more detail in combination with specific examples, which should not be construed as limiting the scope of the protection sought by the present application.

[0033] In the examples, the apparatus shown in FIG. 1 is employed to produce an oxetane derivative, and the synthesis method includes the following steps.

[0034] (1) Weighed amount of 3-ethyl-3-hydroxymethyloxetane (MOX101) and raw material R-(X) n The above are uniformly mixed and placed in the organic raw material storage tank 11, and the alkaline solution and catalyst are uniformly mixed and placed in the alkaline solution storage tank 12.

[0035] (2) The temperatures of the microreactor 20, the first thin film evaporator 40, and the second thin film evaporator 50 are adjusted to the set temperatures, the organic raw material feed pump 101 and the raw material feed pump 102 are started, the raw materials are fed into the micromixer 10 and mixed, and after being retained in the microreactor 20 for a certain period of time, they are fed into the buffer tank 21, and the organic phase is taken and the conversion rate is detected by GC.

[0036] (3) After a certain amount of matter has accumulated in the buffer tank 21, it is transferred to the phase separation tank 30, where the organic phase and the aqueous phase are allowed to stand and separated. The two phases are then transferred to the waste liquid storage tank 31 and the organic phase storage tank 32, respectively.

[0037] (4) The feed pump 103 of the first thin film evaporator is started, the organic phase is separated by the first thin film evaporator 40 to recover excess raw materials, a crude product is obtained, the recovered raw materials are stored in the recovered raw material storage tank 42, and the crude product is stored in the crude product storage tank 41. The feed pump 104 of the second thin film evaporator is started, the crude product is fed into the second thin film evaporator 50 and refined to obtain a product, the final product is stored in the final product storage tank 51, and the reboiled product is stored in the reboiled product storage tank 52. The process parameters in Examples 1 to 9 are shown in Tables 1 and 2.

[0038] [Table 1-1]

[0039] [Table 1-2]

[0040] [Table 2-1]

[0041] [Table 2-2]

[0042] Example 10 This embodiment differs from Example 1 in that the inner diameter of the reaction channel of the microreactor is 200 μm.

[0043] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane is 90.5%, and the yield is 74.6%.

[0044] Example 11 This embodiment differs from Example 1 in that the dimension of the reaction channel of the microreactor is 10,000 μm.

[0045] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 95.2%, and the yield was 76.7 wt%.

[0046] Example 12 This example differs from Example 1 in that the catalyst loading was 1.0%, the catalyst was polyethylene glycol dimethyl ether, and the matter residence time was 5 min.

[0047] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 94.4%, and the yield was 82.4 wt%.

[0048] Example 13 This example differs from Example 1 in that the catalyst loading was 1.0%, the catalyst was 18-crown-6, and the matter residence time was 4 min.

[0049] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 95.2%, and the yield was 81.9 wt%.

[0050] Example 14 This example differs from Example 1 in that the catalyst loading was 1.0%, the catalyst was polyethylene glycol, and the matter residence time was 4 min.

[0051] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 96.2%, and the yield was 80.5 wt%.

[0052] Example 15 This example differs from Example 1 in that the catalyst loading was 1.0%, the catalyst was tetradecyltrimethylammonium chloride, and the matter residence time was 5 min.

[0053] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 95.4%, and the yield was 82.4 wt%.

[0054] Example 16 This example differs from Example 1 in that the reaction temperature for the etherification reaction was 30°C.

[0055] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 92.8%, and the yield was 72.4 wt%.

[0056] Example 17 This embodiment differs from Example 1 in that the dimension of the reaction channel of the microreactor is 12000 μm.

[0057] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 90.8%, and the yield was 67.5 wt%.

[0058] Example 18 The weighed 3-ethyl-3-hydroxymethyloxetane (MOX101), sodium hydroxide, and catalyst are uniformly mixed and placed in an organic raw material storage tank 11, and epichlorohydrin is placed in a raw material storage tank 12. This embodiment differs from Example 1 in that the inner diameter of the reaction flow channel of the microreactor is 500 μm.

[0059] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane is 95.0%, and the yield is 80.6%.

[0060] Example 19 The weighed 3-ethyl-3-hydroxymethyloxetane (MOX101), epichlorohydrin, and catalyst are uniformly mixed and placed in an organic raw material storage tank 11, and an alkaline solution is placed in a raw material storage tank 12. This embodiment differs from Example 1 in that the dimension of the reaction flow channel of the microreactor is 8000 μm.

[0061] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 95.6%, and the yield was 82.3 wt%.

[0062] Example 20 This example differs from Example 1 in that the reaction temperature of the etherification reaction is 100°C.

[0063] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 94.6%, and the yield was 76.1 wt%.

[0064] Example 21 This example differs from Example 1 in that the reaction temperature for the etherification reaction was 5°C.

[0065] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 85.9%, and the yield was 72.4 wt%.

[0066] Example 22 This example differs from Example 1 in that the amount of catalyst added was 0.1%, the catalyst was tetrabutylammonium bromide, and the matter residence time was 5 min.

[0067] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 90.3%, and the yield was 73.5 wt%.

[0068] Example 23 The weighed 3-ethyl-3-hydroxymethyloxetane (MOX101) and sodium hydroxide are mixed uniformly and placed in an organic raw material storage tank 11, and epichlorohydrin and a catalyst are placed in a raw material storage tank 12. This example differs from Example 1 in that the catalyst addition amount is 5%, the catalyst is 18-crown-6, and the matter residence time is 2 min.

[0069] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 92.1%, and the yield was 78.3 wt%.

[0070] Example 24 The weighed 3-ethyl-3-hydroxymethyloxetane (MOX101) and sodium hydroxide are mixed uniformly and placed in an organic raw material storage tank 11, and epichlorohydrin and a catalyst are placed in a raw material storage tank 12. This example differs from Example 1 in that the catalyst addition amount is 4%, the catalyst is tetrabutylammonium bromide, and the matter residence time is 3 minutes.

[0071] The selectivity of 3-ethyl-3-[(oxiranyl-2-methoxy)methyl]oxetane was 91.7%, and the yield was 75.3 wt%.

[0072] In Comparative Examples 1 to 5, a conventional reactor was adopted to produce oxetane derivatives, and the specific process parameters are shown in Table 3. The synthesis method includes the following steps:

[0073] In a four-neck flask, 3-ethyl-3-hydroxymethyloxetane (MOX101) and raw material R-(X) nThe alkaline solution and catalyst were mixed uniformly and added dropwise to the four-neck flask. After the addition was completed, the reaction was carried out while maintaining the temperature. The organic layer was taken and the conversion rate was detected by GC. After the conversion rate no longer changed, the reaction was stopped. The reaction product system was left to stand for phase separation, and then rectified to obtain the final product.

[0074] [Table 3]

[0075] As can be seen from the above description, the embodiments described in the present invention achieve the following technical effects.

[0076] As can be seen from Comparative Examples 1 to 24 and Comparative Examples 1 to 5, the adoption of the method provided by the present application is advantageous in terms of the selectivity and yield of the oxetane derivative.

[0077] As can be seen from Comparative Examples 1, 6, 10, 11, and 17 to 19, limiting the inner diameter of the reaction channel of the microreactor within the range of the present application is advantageous for improving the selectivity and yield of the oxetane derivative.

[0078] As can be seen from Comparative Examples 1, 16, and 20 to 21, limiting the reaction temperature of the etherification reaction to within the range of the present application is advantageous for improving the selectivity and yield of the oxetane derivative.

[0079] The above description is only a preferred embodiment of the present invention, and does not limit the present invention. For those skilled in the art, the present invention may have various modifications and changes. Any modifications, equivalent replacements, improvements, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention. [Explanation of symbols]

[0080] 10 Micro Mixer 11 Organic raw material storage tank 12 Alkaline solution storage tank 20 Microreactor 21 Buffer tank 30 Phase Separation Tank 31 Waste liquid storage tank 32 Organic Phase Storage Tank 40 First thin film evaporator 41 Raw product storage tank 42 Recovered material storage tank 50 Second thin film evaporator 51 Finished product storage tank 52 Reboiler storage tank 101 Organic material feed pump 102 Raw material supply pump 103 First thin film evaporator charge pump 104 Second thin film evaporator feed pump

Claims

1. A method for synthesizing an oxetane derivative represented by the following formula (I) in a microreactor, comprising: 【Chemistry 1】 [In the formula, R is C ２ ~C １２ a linear or branched alkyl group, an alkyl group containing an oxirane structure, an alkyl group containing an oxetane structure, a phenyl group, a tolyl group, a benzyl group, or a biphenyl group, and n is 1 to 4. 3-ethyl-3-hydroxymethyloxetane and a compound of the general formula R-(X) ｎ (X is a halogen element), a catalyst, and an alkali are transported into a microreactor to carry out an etherification reaction to obtain an etherification product system; separating the etherification product system to obtain the oxetane derivative; Including, The inner diameter of the reaction channel of the microreactor is 500 to 8000 μm; A method for synthesizing an oxetane derivative using a microreactor, characterized in that the amount of the catalyst added is 0.5 to 2% by weight based on the weight of the 3-ethyl-3-hydroxymethyloxetane.

2. the alkali is an alkali metal compound or an aqueous solution of an alkali metal compound, the alkali metal compound being one or more selected from the group consisting of lithium hydroxide, sodium hydroxide, potassium hydroxide, and calcium hydroxide, and the concentration of the aqueous solution of the alkali metal compound is 10 to 20%; 2. The method for synthesizing an oxetane derivative using a microreactor according to claim 1, wherein the catalyst is one or more selected from the group consisting of polyethers, cyclic polyethers, and quaternary ammonium salts.

3. The method for synthesizing an oxetane derivative according to claim 2, wherein the alkali metal compound is sodium hydroxide.

4. 3. The method for synthesizing an oxetane derivative using a microreactor according to claim 1 or 2, wherein the catalyst is one or more selected from the group consisting of polyethylene glycol, polyethylene glycol alkyl ether, 18-crown-6, 15-crown-5, tetraethylammonium bromide, tetrabutylammonium bromide, tetrabutylammonium chloride, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, and tetradecyltrimethylammonium chloride.

5. 5. The method for synthesizing an oxetane derivative using a microreactor according to claim 4, wherein the catalyst is one or more selected from the group consisting of polyethylene glycol dimethyl ether, 18-crown-6, and tetrabutylammonium bromide.

6. 2. The method for synthesizing an oxetane derivative using a microreactor according to claim 1, wherein the reaction temperature of the etherification reaction is 10 to 60° C. and the residence time is 2 to 5 minutes.

7. 7. The method for synthesizing an oxetane derivative using a microreactor according to claim 6, wherein the apparatus used in the separation step includes a two-stage thin film evaporator or a rectification column.

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