阅读说明：本技术 通过微反应器合成氧杂环丁烷衍生物的合成方法 (Synthesis method for synthesizing oxetane derivative through microreactor ) 是由 钱晓春 王兵 顾明天 陈君 徐丽萍 于 2021-02-10 设计创作，主要内容包括：本发明提供了一种通过微反应器合成氧杂环丁烷衍生物的合成方法。该合成方法包括：将3-乙基-3-羟甲基氧杂环丁烷、原料Ha、催化剂、碱输送至微反应器中进行醚化反应,得到醚化产物体系,原料Ha的通式为R-(X)-(n),X为卤素；将醚化产物体系进行分离,得到氧杂环丁烷衍生物。利用微反应器可大幅提高反应体系传质传热性,减少反应时间提高生产效率,提高产品收率,并实现过程的连续化、自动化,提高过程安全性。同时上述合成过程所需的反应装置体积小,所需人力资源少,安全性高。(The invention provides a synthetic method for synthesizing an oxetane derivative through a microreactor. The synthesis method comprises the following steps: conveying 3-ethyl-3-hydroxymethyl oxetane, a raw material Ha, a catalyst and alkali into a microreactor for etherification reaction to obtain an etherification product system, wherein the general formula of the raw material Ha is R- (X) n X is halogen; and (4) separating the etherification product system to obtain the oxetane derivative. The mass transfer and heat transfer properties of a reaction system can be greatly improved by using the microreactor, the reaction time is shortened, the production efficiency is improved, the product yield is improved, the continuity and automation of the process are realized, and the process safety is improved. Meanwhile, the reaction device required in the synthesis process is small in size, less in required human resources and high in safety.)

1. A method for synthesizing an oxetane derivative through a microreactor, the oxetane derivative having a structure represented by formula (i):

wherein R is C₂～C₁₂The linear chain or branched chain alkyl group of (1), the alkyl group containing an oxirane structure, the alkyl group containing an oxetane structure, the phenyl group, the tolyl group, the benzyl group or the biphenyl group, and the n is 1 to 4;

the method for synthesizing the oxetane derivative through the microreactor is characterized by comprising the following steps:

conveying 3-ethyl-3-hydroxymethyl oxetane, a raw material Ha, a catalyst and alkali into a microreactor for etherification reaction to obtain an etherification product system, wherein the raw material Ha has a general formula of R- (X)_nAnd X is halogen; and

and separating the etherification product system to obtain the oxetane derivative.

2. The method for synthesizing an oxetane derivative through a microreactor as claimed in claim 1, wherein the microreactor has a reaction channel inner diameter of 200 to 10000 μm.

3. The synthesis method for synthesizing an oxetane derivative through a microreactor as claimed in claim 1, wherein the base is an alkali metal compound or an aqueous solution of an alkali metal compound, 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 10-20%;

the catalyst is selected from one or more of the group consisting of polyethers, cyclic polyethers, and quaternary ammonium salts.

4. The synthesis method for synthesizing an oxetane derivative through a microreactor as claimed in 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 chloride, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride and tetradecyltrimethylammonium chloride.

5. The synthesis method for synthesizing an oxetane derivative through a microreactor as claimed in 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. The method for synthesizing an oxetane derivative through a microreactor as claimed in any of claims 1 to 5, wherein the amount of the catalyst added is 0.1 to 5% in terms of the weight percentage of the 3-ethyl-3-hydroxymethyloxetane.

7. The method for synthesizing an oxetane derivative through a microreactor as claimed in claim 6, wherein the amount of the catalyst added is 0.5 to 2% in weight percentage based on the weight of the 3-ethyl-3-hydroxymethyloxetane.

8. The method for synthesizing an oxetane derivative through a microreactor as claimed in claim 1, wherein the etherification reaction temperature is 10-60 ℃ and the material residence time is 2-5 min.

9. The synthesis process for the synthesis of oxetane derivatives in microreactors as claimed in claim 8, wherein said step of separation employs means comprising: a secondary thin film evaporation device or a rectifying tower.

10. The method for synthesizing an oxetane derivative through a microreactor as claimed in claim 1, wherein the microreactor has a reaction channel inner diameter of 500 to 8000 μm.

Technical Field

The invention relates to the field of organic synthesis, in particular to a synthetic method for synthesizing an oxetane derivative through a microreactor.

Background

3-ethyl-3-hydroxymethyl oxetane is taken as a raw material, and is subjected to etherification reaction with a halogenated organic compound under the action of alkali to obtain a series of oxetane derivatives which can be used as monomers in a photocuring cationic system and applied to the fields of photocuring ink, coating, adhesive and the like, and representative products comprise 3-ethyl-3- [ (ethylene oxide-2-methoxy) methyl ] oxetane, bis [ 1-ethyl (3-oxetanyl) methyl ] ether and 3-benzyloxymethyl-3-ethyl oxetane. These oxetane products are one of the most promising raw materials in the field of cationic photocuring due to their low viscosity, good dilutability, fast crosslinking speed, and excellent properties after film formation.

With 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl group]The oxetane is taken as an example, the oxetane is prepared by taking 3-ethyl-3-hydroxymethyl oxetane and epoxy chloropropane as raw materials and carrying out etherification reaction under the action of solid sodium hydroxide in industrial production, because a reaction system is liquid-solid heterogeneous and has difficult mass transfer, in order to ensure the conversion rate, the epoxy chloropropane and the sodium hydroxide need to be over 50 percent, and the amount is 2m³The reaction kettle is used for production, the reaction process is about 12 hours, the working procedures of post-treatment including filtration, rectification and the like require about 30 hours, and the operation of adding solid sodium hydroxide in batches in the production process is complicated and has potential safety hazards such as temperature runaway and the like.

In view of the above problems, it is desirable to provide a method for synthesizing an oxetane derivative which is short in reaction time, high in mass transfer efficiency, and excellent in safety.

Disclosure of Invention

The invention mainly aims to provide a method for synthesizing an oxetane derivative through a microreactor, which solves the problems of long reaction time, complex operation and poor safety in the existing method for synthesizing the oxetane derivative. The selectivity of etherification reaction is ensured and the product yield is improved while the continuous production is realized.

In order to achieve the above object, the present invention provides a synthesis method for synthesizing an oxetane derivative through a microreactor, the oxetane derivative having a structure represented by formula (i):

wherein R is C₂～C₁₂The linear chain or branched alkyl group, the alkyl group containing an oxirane structure, the alkyl group containing an oxetane structure, the phenyl group, the tolyl group, the benzyl group or the biphenyl group, and n is 1 to 4; the synthesis method for synthesizing the oxetane derivative through the microreactor comprises the following steps: conveying 3-ethyl-3-hydroxymethyl oxetane, a raw material Ha, a catalyst and alkali into a microreactor for etherification reaction to obtain an etherification product system, wherein the general formula of the raw material Ha is R- (X)_nX is halogen; and separating the etherification product system to obtain the oxetane derivative.

Furthermore, the inner diameter of the reaction channel of the microreactor is 200-10000 μm.

Further, the alkali is an alkali metal compound or an aqueous solution of an alkali metal compound, 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 percent; the catalyst is selected from one or more of the group consisting of polyethers, cyclic polyethers, and quaternary ammonium salts.

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

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

Furthermore, the catalyst is added in an amount of 0.1-5% by weight based on the weight of 3-ethyl-3-hydroxymethyl oxetane.

Furthermore, the catalyst is added in an amount of 0.5-2% by weight based on the weight of 3-ethyl-3-hydroxymethyl oxetane.

Further, the reaction temperature of the etherification reaction is 10-60 ℃, and the material retention time is 2-5 min.

Further, the step of separating employs an apparatus comprising: a secondary thin film evaporation device or a rectifying tower.

Furthermore, the inner diameter of the reaction channel of the microreactor is 500-8000 mu m.

Compared with the conventional reactor, the micro-reactor has the advantages of high heat and mass transfer coefficient, good mixing performance, easy temperature control, safe and controllable process and the like. The advantages of the microreactor are utilized to prepare the oxetane derivative, so that the mass transfer and heat transfer properties of a reaction system can be greatly improved, the reaction time is shortened, the production efficiency is improved, the product yield is improved, the continuity and automation of the process are realized, and the process safety is improved. Limiting the pore size of the reaction channel of the microreactor within the above range is advantageous for increasing the selectivity of the etherification reaction and thus for increasing the conversion of the oxetane derivative. In addition, the reaction device required by the synthesis process is small in size, small in occupied area of a production field, less in required human resources and high in safety.

Drawings

The accompanying drawings, which are incorporated in and constitute a part of this application, illustrate embodiments of the invention and, together with the description, serve to explain the invention and not to limit the invention. In the drawings:

fig. 1 shows a schematic structural view of an apparatus for preparing an oxetane derivative, provided according to an exemplary embodiment of the present invention.

Wherein the figures include the following reference numerals:

10. a micro mixer; 11. an organic matter raw material storage tank; 12. an alkali solution storage tank; 20. a microreactor; 21. a buffer tank; 30. a phase splitting tank; 31. a waste water storage tank; 32. an organic phase storage tank; 40. a first-stage thin film evaporator; 41. a crude product storage tank; 42. a raw material recovery storage tank; 50. a secondary thin film evaporator; 51. a finished product storage tank; 52. a reboiled tanks;

101. an organic material feed pump; 102. a raw material feed pump; 103. a feed pump of the first-stage thin film evaporator; 104. a feed pump of the second-stage film evaporator.

Detailed Description

It should be noted that the embodiments and features of the embodiments in the present application may be combined with each other without conflict. The present invention will be described in detail with reference to examples.

As described in the background art, the existing methods for synthesizing oxetane derivatives have problems of 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 an oxetane derivative through a microreactor, the oxetane derivative having a structure represented by formula (i):

wherein R is C₂～C₁₂The linear chain or branched alkyl group, the alkyl group containing an oxirane structure, the alkyl group containing an oxetane structure, the phenyl group, the tolyl group, the benzyl group or the biphenyl group, and n is 1 to 4; the synthesis method of the oxetane derivative comprises the following steps: 3-ethyl-3-hydroxymethyl oxetane, a raw material Ha, a catalyst and a base are conveyed to a micro-reactorCarrying out etherification reaction in a reactor to obtain an etherification product system, wherein the general formula of the raw material Ha is R- (X)_nWherein X is halogen; and separating the etherification product system to obtain the oxetane derivative.

Compared with the conventional reactor, the microreactor has the advantages of high heat and mass transfer coefficients, good mixing performance, easy temperature control, safe and controllable process and the like. The advantages of the microreactor are utilized to prepare the oxetane derivative, so that the mass transfer and heat transfer properties of a reaction system can be greatly improved, the reaction time is shortened, the production efficiency is improved, the product yield is improved, the continuity and automation of the process are realized, and the process safety is improved. In addition, the reaction device required by the synthesis process is small in size, small in occupied area of a production field, less in required human resources and high in safety.

Preferably, the inner diameter of the reaction channel of the microreactor is 200-10000 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 of the oxetane derivative. For example, the inner diameter of the reaction channel of the microreactor is 200 μm, 500 μm, 4000 μm, 6000 μm, 8000 μm, 10000 μm, and more preferably, the inner diameter of the reaction channel of the microreactor is 500 to 8000 μm.

In the above synthesis method, the base is an alkali metal compound or an aqueous solution of an alkali metal compound. The alkali metal compound may be selected from those commonly used in the art. Preferably, the alkali metal compound includes, but is not limited to, one or more of 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%.

The catalyst used in the above synthesis method may be any one of those commonly used in the art, and the catalyst includes, but is not limited to, one or more of the group consisting of polyethers, cyclic polyethers, and quaternary ammonium salts. Preferably, the catalyst includes, but is not limited to, one or more of the group consisting of polyethylene glycol, polyethylene glycol alkyl ether, 18-crown-6, 15-crown-5, tetraethylammonium bromide, tetrabutylammonium chloride, trioctylmethylammonium chloride, dodecyltrimethylammonium chloride, and tetradecyltrimethylammonium chloride. Compared with other catalysts, the catalysts are favorable for further improving the reaction rate of etherification reaction and shortening the reaction period. More preferably, the catalyst includes, but is not limited to, one or more of the group consisting of dimethyl ether of polyethylene glycol, 18-crown-6, and tetrabutylammonium bromide.

In a preferred embodiment, the catalyst is added in an amount of 0.1 to 5% by weight based on the weight of 3-ethyl-3-hydroxymethyloxetane. The amount of the catalyst used includes, but is not limited to, the above range, and it is preferable to limit the amount to the above range to further increase the reaction rate of the etherification reaction. For example, the amount of catalyst added may be 0.1%, 0.5%, 1%, 1.5%, 2%, 3%, 4% by weight based on the weight of 3-ethyl-3-hydroxymethyloxetane. More preferably, the amount of the catalyst is 0.5-2% by weight based on the weight of 3-ethyl-3-hydroxymethyl oxetane.

In a preferred embodiment, the molar ratio of 3-ethyl-3-hydroxymethyloxetane to halogen in the starting material Ha is 1: (1.0-1.2). The molar ratio of 3-ethyl-3-hydroxymethyloxetane to halogen in the raw material Ha includes, but is not limited to, the above range, and it is defined in the above range to be advantageous in improving the conversion of 3-ethyl-3-hydroxymethyloxetane.

In a preferred embodiment, the reaction temperature of the etherification reaction is 10-60 ℃, and the material retention time is 2-5 min. The reaction temperature and the material residence time of the etherification reaction include, but are not limited to, the above ranges, and it is advantageous to further improve the yield of the etherification product by limiting them to the above ranges. For example, the reaction temperature for the etherification reaction may be 10 ℃, 20 ℃, 30 ℃, 40 ℃, 50 ℃ and 60 ℃.

The above separation step may be carried out using an apparatus commonly used in the art. Preferably, the step of separating employs an apparatus comprising: a secondary thin film evaporation device or a rectifying tower.

The present application is described in further detail below with reference to specific examples, which should not be construed as limiting the scope of the invention as claimed.

Examples oxetane derivatives were prepared using the apparatus shown in fig. 1, and the synthesis method included:

(1) the metered 3-ethyl-3-hydroxymethyl oxetane (MOX101) and the raw material R- (X) n are uniformly mixed and put into an organic material storage tank 11, and the alkaline solution and the catalyst are uniformly mixed and put into an alkaline solution storage tank 12.

(2) Adjusting the temperature of the microreactor 20, the first-stage thin-film evaporator 40 and the second-stage thin-film evaporator 50 to a set temperature, starting the organic raw material feeding pump 101 and the raw material feeding pump 102 to enable the raw materials to enter the micromixer 10 for mixing, staying in the microreactor 20 for a certain time, then entering the buffer tank 21, and taking an organic phase GC to detect the conversion rate.

(3) After a certain amount of materials are accumulated in the buffer tank 21, the materials enter a phase separation tank 30, an organic phase and a water phase are kept stand and separated, and the two phases respectively enter a waste water storage tank 31 and an organic phase storage tank 32.

(4) Starting a feeding pump 103 of the first-stage film evaporator, separating and recovering excessive raw materials from an organic phase by the first-stage film evaporator 40 to obtain a crude product, storing the recovered raw materials in a recovered raw material storage tank 42, and storing the crude product in a crude product storage tank 41; and starting a feed pump 104 of the secondary film evaporator, feeding the crude product into the secondary film evaporator 50, purifying to obtain a product, storing the finished product in a finished product storage tank 51, and storing the heavy boilers in a heavy boiler storage tank 52. The process parameters in examples 1 to 9 are shown in tables 1 and 2.

TABLE 1

TABLE 2

Example 10

The differences from example 1 are: the inner diameter of the reaction channel of the microreactor was 200. mu.m.

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

Example 11

The differences from example 1 are: the size of the reaction channel of the microreactor was 10000. mu.m.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 95.2%, and the yield was 76.7% by weight.

Example 12

The differences from example 1 are: the addition amount of the catalyst is 1.0 percent, the catalyst is polyethylene glycol dimethyl ether, and the retention time of the materials is 5 min.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 94.4%, and the yield was 82.4% by weight.

Example 13

The differences from example 1 are: the addition amount of the catalyst is 1.0 percent, the catalyst is 18-crown-6, and the material retention time is 4 min.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 95.2%, and the yield was 81.9% by weight.

Example 14

The differences from example 1 are: the addition amount of the catalyst is 1.0 percent, the catalyst is polyethylene glycol, and the material retention time is 4 min.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 96.2%, and the yield was 80.5% by weight.

Example 15

The differences from example 1 are: the addition amount of the catalyst is 1.0 percent, the catalyst is tetradecyltrimethylammonium chloride, and the material retention time is 5 min.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 95.4%, and the yield was 82.4% by weight.

Example 16

The differences from example 1 are: the reaction temperature for the etherification reaction was 30 ℃.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 92.8%, and the yield was 72.4% by weight.

Example 17

The differences from example 1 are: the size of the reaction channel of the microreactor was 12000. mu.m.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 90.8%, and the yield was 67.5% by weight.

Example 18

The differences from example 1 are: uniformly mixing 3-ethyl-3-hydroxymethyl oxetane (MOX101), flake caustic soda and a catalyst, putting the mixture into an organic raw material storage tank 11, and putting epichlorohydrin into a raw material storage tank 12. The inner diameter of the reaction channel of the microreactor was 500. mu.m.

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

Example 19

The differences from example 1 are: the method comprises the steps of uniformly mixing metered 3-ethyl-3-hydroxymethyl oxetane (MOX101), epoxy chloropropane and a catalyst, filling the mixture into an organic raw material storage tank 11, and filling an alkali solution into a raw material storage tank 12. The size of the reaction channel of the microreactor is 8000 μm.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 95.6%, and the yield was 82.3% by weight.

Example 20

The differences from example 1 are: the reaction temperature for the etherification reaction was 100 ℃.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 94.6%, and the yield was 76.1% by weight.

Example 21

The differences from example 1 are: the reaction temperature for the etherification reaction was 5 ℃.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 85.9%, and the yield was 72.4% by weight.

Example 22

The differences from example 1 are: the addition amount of the catalyst is 0.1 percent, the catalyst is tetrabutylammonium bromide, and the material retention time is 5 min.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 90.3%, and the yield was 73.5% by weight.

Example 23

The differences from example 1 are: uniformly mixing 3-ethyl-3-hydroxymethyl oxetane (MOX101) and flake caustic soda, putting into an organic raw material storage tank 11, and putting epichlorohydrin and a catalyst into a raw material storage tank 12. The catalyst addition is 5%, the catalyst is 18-crown-6, and the material retention time is 2 min.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 92.1%, and the yield was 78.3% by weight.

Example 24

The differences from example 1 are: uniformly mixing 3-ethyl-3-hydroxymethyl oxetane (MOX101) and flake caustic soda, putting into an organic raw material storage tank 11, and putting epichlorohydrin and a catalyst into a raw material storage tank 12. The catalyst is added in 4 percent, the catalyst is tetrabutylammonium bromide, and the material retention time is 3 min.

The selectivity for 3-ethyl-3- [ (oxiranyl-2-methoxy) methyl ] oxetane was 91.7%, and the yield was 75.3% by weight.

Comparative examples 1 to 5 oxetane derivatives were prepared using a conventional reactor, the specific process parameters are shown in table 3, and the synthesis method comprises:

adding a 3-ethyl-3-hydroxymethyl oxygen heterocyclic ring (MOX101) and a raw material R- (X) n into a four-neck flask, starting stirring and uniformly mixing, uniformly mixing an alkali solution and a catalyst, dropwise adding into the four-neck flask, keeping the temperature after dropwise adding is finished, reacting, taking an organic layer GC to detect the conversion rate, and stopping the reaction after the conversion rate is not changed any more. And (3) standing and phase splitting the reaction product system, and then rectifying to obtain a finished product.

TABLE 3

From the above description, it can be seen that the above-described embodiments of the present invention achieve the following technical effects:

comparing examples 1 to 24 and comparative examples 1 to 5, it can be seen that the process provided herein was selected to favor selectivity and yield of the oxetane derivative.

Comparing examples 1, 6, 10, 11, 17 to 19, it is found that limiting the inner diameter of the microreactor reaction channel within the range of the present application is advantageous in increasing the selectivity and yield of the oxetane derivative.

Comparing examples 1, 16, 20 and 21, it is understood that limiting the reaction temperature of the etherification reaction within the range of the present application is advantageous in improving the selectivity and yield of the oxetane derivative.

The above description is only a preferred embodiment of the present invention and is not intended to limit the present invention, and various modifications and changes may be made by those skilled in the art. Any modification, equivalent replacement, or improvement made within the spirit and principle of the present invention should be included in the protection scope of the present invention.