Method and system for synthesizing 3-(alpha-methoxy)-methylene benzofuran-2-(3H)-ketone

Abstract

The invention relates to the technical field of organic synthesis, in particular to a method for synthesizing 3-(alpha-methoxyl)-methylene benzofuran-2-(3H)-ketone, which comprises the following steps: S1, respectively dissolving benzofuranone and trimethyl orthoformate in a solvent, and heating the two obtained solutions in an oil bath; s2, pumping the two heated solutions into a microreactor through a metering pump for mixing and reacting, after the reaction is finished, feeding the obtained material into a gas-liquid separation device to remove tail gas, and absorbing the tail gas with water; and S3, post-treatment process: carrying out negative pressure concentration on the separated feed liquid to obtain black oily matter, then mixing the obtained black oily matter with a crystallizing agent, firstly heating for dissolving, then cooling for crystallizing, finally filtering to obtain a wet material, and drying the obtained wet material to obtain the product. According to the invention, benzofuranone and trimethyl orthoformate are respectively dissolved in acetic anhydride, the temperature is controlled by oil bath, and continuous contact is carried out through the microchannel reactor, so that the synthesis efficiency and safety of the product are improved.

Description

Technical Field

[0001] The present invention relates to the technical field of organic synthesis, and in particular to a method and system for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one. Background Art

[0002] 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one is an organic compound. Its core structure is benzofuran-2-(3H)-one as can be seen from the name. Benzofuran is a heterocyclic compound formed by the fusion of a benzene ring and a furan ring. The furan ring contains an oxygen atom. A special substituent, i.e., (α-methoxy)-methenyl, is connected to the 3-position of this structure. 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one is an important intermediate for the synthesis of the fungicide azoxystrobin. At present, the production of this product adopts a traditional autoclave reactor for synthesis, which has high requirements on production equipment and high risks of intermittent operation.

[0003] For example, Chinese patent CN102942543 discloses a method for preparing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one, in the presence of an aromatic hydrocarbon solvent, adding a certain proportion of trimethyl orthoformate and acetic anhydride to benzofuranone, heating to 105-115° C., collecting fractions with a temperature not higher than 70° C., and after 12 hours, no more fractions are distilled out, distilling to recover methyl acetate, distilling it out again, concentrating the reaction solution under reduced pressure, recovering the aromatic hydrocarbon solvent, and returning it to the reaction system for recycling, adding methanol solvent to the reaction product, mixing, cooling, crystallizing, filtering, and drying to obtain the product.

[0004] The above invention effectively utilizes the characteristics of aromatic hydrocarbon solvents to improve the mass transfer and heat transfer efficiency of the reaction, reduces the amount of acetic anhydride used, and can prepare high-quality products. However, the process is relatively complicated, and there are many types of solvents for distillation and purification. The problem of by-product methyl acetate cannot be solved, which is not conducive to industrial production. Similarly, Chinese patent CN103333145 also uses aromatic hydrocarbons as reaction solvents and methanol as crystallization solvents, and its disadvantages are also the same. Chinese patent CN102417498 adopts a solvent-free method (benzofuranone, acetic anhydride and trimethyl orthoformate are mixed in a certain ratio and then reacted). According to its reaction mechanism and the shortcomings of the kettle reactor, the process requires excessive addition of raw materials acetic anhydride and trimethyl orthoformate and a long reaction time.

[0005] In this step, the trimethyl orthoformate first removes a methoxy group to form a carbon cation, and at the same time, the benzofuran-2(3H)-one molecule rearranges, and the carbon cation attacks the double bond to undergo a nucleophilic addition reaction (the reaction rate is slow), and then removes a methoxy group through an elimination reaction, thereby introducing a methoxymethyl group on the benzofuran-2(3H)-one. Acetic anhydride is both a reaction solvent and a methanol removal agent in this reaction. It can be seen that this reaction is a slow reaction. If the process route and reactor cannot guarantee high efficiency of mass transfer and heat transfer, the reaction will take too long and is not conducive to industrial production.

[0006] Based on this, the present invention provides a method for synthesizing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one to solve the above-mentioned technical problems. Summary of the invention

[0007] The object of the present invention is to provide a method and system for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one, which adopts a kettle-type device different from the traditional batch synthesis, greatly reduces the reaction time, improves the mass transfer efficiency and safety of the reaction, and solves the above-mentioned problems.

[0008] To achieve the above object, the present invention provides the following technical solutions: A method for synthesizing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one comprises the following steps: S1, dissolving benzofuranone and trimethyl orthoformate in solvents respectively, and heating the obtained two solutions in an oil bath; S2, the two heated solutions are pumped into the microreactor through a metering pump for mixing and reaction. After the reaction is completed, the resulting materials enter a gas-liquid separation device to remove tail gas, and the tail gas is absorbed by water; S3, post-processing process: the separated liquid is concentrated under negative pressure to obtain a black oily substance, and then the obtained black oily substance is mixed with a crystallizing agent, first heated to dissolve and then cooled to crystallize, and finally filtered to obtain a wet material, and the obtained wet material is dried to obtain the product.

[0009] Furthermore, in the step S1, the molar ratio of the benzofuranone, the solvent and trimethyl orthoformate is 1:2.0-2.2:1.0-1.1.

[0010] Furthermore, in step S1, the solvent is acetic anhydride.

[0011] Furthermore, in the step S1, heating in the oil bath refers to heating the temperature to 80-90°C.

[0012] Furthermore, in the step S2, the reaction temperature is 105-110° C., and the reaction residence time is 20-30 min.

[0013] Furthermore, in step S3, the crystallization agent is methyl acetate.

[0014] Furthermore, in step S3, the fractions after the negative pressure concentration of the feed liquid are collected, methyl acetate is recovered by distillation, and returned to the post-processing step as a crystallizing agent.

[0015] Furthermore, in the step S3, the crystallization temperature is -5 to 0°C.

[0016] Furthermore, in step S3, the drying temperature is 60-65°C.

[0017] Further, in step S2, the microreactor includes a base, a controller, a reaction tank, a discharge pipe and a feed pipe, one end of the base is fixedly installed with both ends of the controller, the top of the base is fixedly connected to the bottom of the reaction tank, and a heating component is fixedly installed inside the base, one end of the reaction tank is fixedly connected to one end of the feed pipe, and the other end of the reaction tank is fixedly connected to one end of the discharge pipe, a mixed reaction channel is arranged inside the reaction tank, a straight channel is arranged at one end of the mixed reaction channel, and an outflow channel is arranged at the other end of the mixed reaction channel, the cross-section of the mixed reaction channel is rectangular or circular, the width of the straight channel is 60-600μm, and the width of the mixed reaction channel is 200-1200μm.

[0018] Beneficial effects of the present invention: 1. In the present invention, the method uses benzofuranone as a raw material, dissolves it and trimethyl orthoformate in acetic anhydride respectively, controls the temperature in an oil bath, adopts a kettle-type device different from the traditional intermittent synthesis, continuously contacts through a microchannel reactor, and directly reacts in one step, which greatly improves the synthesis efficiency and safety of the product. The synthesized product has a high content and yield, the product content is greater than 98% (in terms of mass percentage), and the yield is greater than 92% (in terms of benzofuranone). The method for synthesizing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one provided by the present invention has a broader market prospect and is more suitable for promotion.

[0019] 2. In the present invention, the microreactor is a miniaturized reaction vessel prepared based on microfluidic technology, and the inner wall of the vessel adopts a micron-level channel structure. Compared with the traditional kettle reactor, the microchannel reactor has the advantages of rapid heat and mass transfer, efficient reaction, energy saving and emission reduction. It is precisely because of the excellence of the microchannel reactor that the feed ratio of raw materials acetic anhydride, trimethyl orthoformate and benzofuranone is greatly reduced, which not only saves raw material costs and reduces safety risks, but also improves the conversion efficiency of the reaction.

[0020] 3. In the present invention, the solvent used for crystallization is methyl acetate. The solubility-temperature curve of the product in methyl acetate shows a steeper upward trend than that in methanol, that is, the crystallization effect is better. At the same time, a large amount of methyl acetate and acetic acid are generated in the reaction system. The fractions after the feed liquid is concentrated by negative pressure are collected, and methyl acetate is recovered by distillation and recycled in the post-processing process as a crystallizing agent for the product. BRIEF DESCRIPTION OF THE DRAWINGS

[0021] Figure 1 The schematic diagram of a method for synthesizing 3-(α-methoxy)-methylbenzenebenzofuran-2-(3H)-one of the present invention; Figure 2 The present invention is a flow chart of a method for synthesizing 3-(α-methoxy)-methylbenzenebenzofuran-2-(3H)-one; Figure 3 A schematic structural diagram of a microreactor for a method of synthesizing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one according to the present invention; Figure 4 A schematic diagram of the top view of a microreactor for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one according to the present invention; Figure 5 The front cross-sectional view of a microreactor of a method for synthesizing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one of the present invention.

[0022] In the figure: 1. base; 2. controller; 3. reaction tank; 4. discharge pipe; 5. heating component; 6. feed pipe; 7. linear channel; 8. mixing reaction channel; 9. outflow channel. DETAILED DESCRIPTION

[0023] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0024] Example 1: Figure 1-Figure 5 As shown, this design proposes an implementation method, a method for synthesizing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one: 134 g (1 mol) of benzofuranone was dissolved in 150 g (1.47 mol) of acetic anhydride, and 116.7 g (1.1 mol) of trimethyl orthoformate was mixed with 64.2 g (0.63 mol) of acetic anhydride.

[0025] The two materials were heated to 85°C in an oil bath and continuously fed into a microreactor through two metering pumps for mixing and reaction. The reaction temperature was 105°C and the residence time was 25 min. The obtained materials were fed into a gas-liquid separation device for gas-liquid separation, and the gas was fed into an absorption device and the liquid into a post-treatment kettle.

[0026] Post-processing method: The above-mentioned liquid was concentrated under negative pressure to obtain a black oily substance, and then the oily substance was mixed with methyl acetate, first heated to dissolve and then cooled to -5°C to crystallize, and finally filtered to obtain a wet material. The obtained wet material was dried in a drying oven at 60°C for 2h to obtain 168.3g of a finished product.

[0027] Example 2: Figure 1-Figure 5 As shown, this design proposes an implementation method, a method for synthesizing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one: 134 g (1 mol) of benzofuranone was dissolved in 150 g (1.47 mol) of acetic anhydride, and 111.4 g (1.05 mol) of trimethyl orthoformate was mixed with 64.2 g (0.63 mol) of acetic anhydride.

[0028] The two materials were heated to 90°C in an oil bath and continuously fed into a microreactor through two metering pumps for mixing and reaction. The reaction temperature was 110°C and the residence time was 25 min. The materials entered a gas-liquid separation device for gas-liquid separation, and the gas was passed into an absorption device and the liquid into a post-treatment kettle.

[0029] Then the post-treatment was carried out in the same manner as in Example 1 to obtain 166.8 g of finished product.

[0030] Example 3: Figure 1-Figure 5 As shown, this design proposes an implementation method, a method for synthesizing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one: 134 g (1 mol) of benzofuranone was dissolved in 150 g (1.47 mol) of acetic anhydride, and 106.1 g (1 mol) of trimethyl orthoformate was mixed with 64.2 g (0.63 mol) of acetic anhydride.

[0031] The oil bath temperature of the two materials was raised to 80°C, and they were continuously fed into the microreactor through two metering pumps for mixing and reaction. The reaction temperature was 110°C and the residence time was 30 minutes. The materials entered the gas-liquid separation device for gas-liquid separation, and the gas was passed into the absorption device and the liquid into the post-treatment kettle.

[0032] Then the post-treatment was carried out in the same manner as in Example 1 to obtain 165.8 g of finished product.

[0033] Example 4: Figure 1-Figure 5 As shown, this design proposes an implementation method, a method for synthesizing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one: 134 g (1 mol) of benzofuranone was dissolved in 150 g (1.47 mol) of acetic anhydride, and 116.7 g (1.1 mol) of trimethyl orthoformate was mixed with 74.4 g (0.73 mol) of acetic anhydride.

[0034] The oil bath temperature of the two materials was raised to 85°C, and they were continuously fed into the microreactor through two metering pumps for mixing and reaction. The reaction temperature was 105°C and the residence time was 25 minutes. The materials entered the gas-liquid separation device for gas-liquid separation, and the gas was passed into the absorption device and the liquid into the post-treatment kettle.

[0035] Then the post-treatment was carried out in the same manner as in Example 1 to obtain 166.4 g of finished product.

[0036] Among them, in Examples 1 to 4, a large amount of methyl acetate and acetic acid are generated in the crystallization reaction system, and the fractions after the feed liquid is concentrated by negative pressure are collected, methyl acetate is recovered by distillation, and returned to the post-processing process as a crystallizing agent; the microreactor includes a base 1, a controller 2, a reaction tank 3, a discharge pipe 4 and a feed pipe 6, one end of the base 1 is fixedly installed with both ends of the controller 2, the top of the base 1 is fixedly connected to the bottom of the reaction tank 3, and a heating component 5 is fixedly installed inside the base 1, one end of the reaction tank 3 is fixedly connected to one end of the feed pipe 6, and the other end of the reaction tank 3 is fixedly connected to one end of the discharge pipe 4, a mixed reaction channel 8 is arranged inside the reaction tank 3, one end of the mixed reaction channel 8 is arranged with a straight channel 7, and the other end of the mixed reaction channel 8 is arranged with an outflow channel 9, the cross-section of the mixed reaction channel 8 is rectangular or circular, the width of the straight channel 7 is 60-600 μm, and the width of the mixed reaction channel 8 is 200-1200 μm.

[0037] Comparative Example 1: The difference from Example 1 is that in this example, the temperature is not raised by an oil bath, but the reaction directly enters the microchannel.

[0038] Comparative Example 2: The difference from Example 1 is that the residence time in this example is 10 min.

[0039] Comparative Example 3: The difference from Example 1 is that the reaction temperature in this example is 90°C.

[0040] Comparative Example 4: The difference from Example 1 is that methanol crystallization is used in this example.

[0041] Performance test: The methods for synthesizing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one provided in Examples 1 to 4 and Comparative Examples 1 to 4 are respectively marked as Examples 1 to 4 and Comparative Examples 1 to 4; and the relevant properties of 3-(α-methoxy)-methylbenzofuran-2-(3H)-one obtained by the methods of Examples 1 to 4 and Comparative Examples 1 to 4 are respectively tested as follows.

[0042]

[0043]

[0044] By comparing and analyzing the relevant data in Table 1 and Table 2, it can be seen that the differences in finished product content and yield between Example 1 group to Example 4 group are not obvious, and each group has excellent finished product content and yield.

[0045] Compared with Example 1, the raw materials of Comparative Group 1 were not preheated before entering the reactor, resulting in insufficient residence time for the reaction and incomplete reaction. The finished product content and yield were significantly lower than those of Example 1.

[0046] Compared with Example 1, the reaction of Comparative Group 2 was incomplete, a large amount of raw materials were not reacted, and the finished product content and yield were significantly lower than those of Example 1.

[0047] Compared with Example 1, the reaction temperature of Comparative Group 3 was not high enough to reduce the activation energy of the reaction, thereby failing to further promote the reaction. The finished product content and yield were also significantly lower than those of Example 1.

[0048] Compared with Example 1, at low temperature, the solubility of the finished product in methanol of Comparative 4 was higher than that in methyl acetate, and the yield was significantly lower than that of Example 1.

[0049] In summary, the method for synthesizing 3-(α-methoxy)-methylbenzenebenzofuran-2-(3H)-one provided by the present invention comprises the following steps: dissolving benzofuranone and trimethyl orthoformate in acetic anhydride respectively, placing the obtained two solutions in an oil bath and heating them to 80-90° C.; pumping the heated two solutions into a microreactor through a metering pump for mixing and reacting (the reaction temperature is 105-110° C., and the reaction residence time is 20-30 min); after the reaction is completed, the obtained material enters a gas-liquid separation device to remove tail gas (the gas is passed into an absorption device, and the liquid is passed into a post-treatment kettle), and the tail gas is absorbed by water; then the separated feed liquid is concentrated under negative pressure to obtain a black oily substance, and then the obtained black oily substance is mixed with methyl acetate, first heated to dissolve and then cooled to crystallize (the crystallization temperature is -5-0° C.), and finally filtered to obtain a wet material, and the obtained wet material is dried in a drying oven (the drying temperature is 60-65° C.) to obtain a product; The method uses benzofuranone as a raw material, dissolves it and trimethyl orthoformate in acetic anhydride respectively, controls the temperature by an oil bath, adopts a kettle-type device different from the traditional intermittent synthesis, continuously contacts through a microchannel reactor, and directly reacts in one step, thereby greatly improving the synthesis efficiency and safety of the product. The synthesized product has a high content and yield, the product content is greater than 98% (in terms of mass percentage), and the yield is greater than 92% (in terms of benzofuranone), which indicates that the method for synthesizing 3-(α-methoxy)-methylbenzofuran-2-(3H)-one provided by the present invention has a broader market prospect and is more suitable for promotion; Among them, a large amount of methyl acetate and acetic acid will be generated in the crystallization reaction system. The fractions after the feed liquid is concentrated by negative pressure are collected, the methyl acetate is recovered by distillation, and returned to the post-processing process as a crystallizing agent; the microreactor includes a base 1, a controller 2, a reaction tank 3, a discharge pipe 4 and a feed pipe 6, one end of the base 1 is fixedly installed with both ends of the controller 2, the top of the base 1 is fixedly connected with the bottom of the reaction tank 3, and a heating component 5 is fixedly installed inside the base 1, one end of the reaction tank 3 is fixedly connected with one end of the feed pipe 6, and the other end of the reaction tank 3 is fixedly connected with one end of the discharge pipe 4, a mixed reaction channel 8 is arranged inside the reaction tank 3, one end of the mixed reaction channel 8 is arranged with a straight channel 7, and a mixed The other end of the reaction channel 8 is provided with an outflow channel 9, the cross section of the mixed reaction channel 8 is rectangular or circular, the width of the straight channel 7 is 60-600 μm, and the width of the mixed reaction channel 8 is 200-1200 μm; a microchannel reactor (microreactor) is a miniaturized reaction vessel prepared based on microfluidic technology, and the inner wall of the vessel adopts a micron-level channel structure. Compared with the traditional kettle reactor, the microchannel reactor has the advantages of rapid heat and mass transfer, efficient reaction, energy saving and emission reduction. It is precisely because of the excellence of the microchannel reactor that the feed ratio of raw materials acetic anhydride, trimethyl orthoformate and benzofuranone is greatly reduced, which not only saves raw material costs and reduces safety risks, but also improves the conversion efficiency of the reaction; At the same time, the solvent used for crystallization is methyl acetate. The solubility-temperature curve of the product in methyl acetate shows a steeper upward trend than that in methanol, that is, the crystallization effect is better. At the same time, a large amount of methyl acetate and acetic acid will be generated in the reaction system. The fractions after the feed liquid is concentrated by negative pressure are collected, and methyl acetate is recovered by distillation and recycled in the post-processing process as a crystallizing agent for the product.

[0050] In the description of this specification, the description with reference to the terms "one embodiment", "example", "specific example", etc. means that the specific features, structures, materials or characteristics described in conjunction with the embodiment or example are included in at least one embodiment or example of the present invention. In this specification, the schematic representation of the above terms does not necessarily refer to the same embodiment or example. Moreover, the specific features, structures, materials or characteristics described can be combined in any one or more embodiments or examples in a suitable manner.

[0051] The preferred embodiments of the present invention disclosed above are only used to help illustrate the present invention. The preferred embodiments do not describe all the details in detail, nor do they limit the invention to the specific implementation methods described. Obviously, many modifications and changes can be made according to the content of this specification. This specification selects and specifically describes these embodiments in order to better explain the principles and practical applications of the present invention, so that those skilled in the art can understand and use the present invention well. The present invention is limited only by the claims and their full scope and equivalents.

Claims

1. A method for synthesizing 3-(α-methoxy)-methylbenzenebenzofuran-2-(3H)-one, characterized in that: The following steps are involved: S1, dissolving benzofuranone and trimethyl orthoformate in solvents respectively, and heating the obtained two solutions in an oil bath; S2, the two heated solutions are pumped into the microreactor through a metering pump for mixing and reaction. After the reaction is completed, the resulting materials enter a gas-liquid separation device to remove tail gas, and the tail gas is absorbed by water; S3, post-processing process: the separated liquid is concentrated under negative pressure to obtain a black oily substance, and then the obtained black oily substance is mixed with a crystallizing agent, first heated to dissolve and then cooled to crystallize, and finally filtered to obtain a wet material, and the obtained wet material is dried to obtain the product.

2. The method for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one according to claim 1, characterized in that: In the step S1, the molar ratio of the benzofuranone, the solvent and trimethyl orthoformate is 1:2.0-2.2:1.0-1.

1.

3. The method for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one according to claim 1, characterized in that: In the step S1, the solvent is acetic anhydride.

4. The method for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one according to claim 1, characterized in that: In the step S1, heating in the oil bath means raising the temperature to 80-90°C.

5. The method for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one according to claim 1, characterized in that: In the step S2, the reaction temperature is 105-110°C, and the reaction residence time is 20-30 minutes.

6. The method for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one according to claim 1, characterized in that: In step S3, methyl acetate is selected as the crystallizing agent.

7. The method for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one according to claim 1, characterized in that: In step S3, the fractions after the negative pressure concentration of the feed liquid are collected, methyl acetate is recovered by distillation, and is returned to the post-processing step as a crystallizing agent.

8. The method for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one according to claim 1, characterized in that: In the step S3, the crystallization temperature is -5 to 0°C.

9. The method for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one according to claim 1, characterized in that: In the step S3, the drying temperature is 60-65°C.

10. The method for synthesizing 3-(α-methoxy)-methenylbenzofuran-2-(3H)-one according to claim 1, characterized in that: In step S2, the microreactor comprises a base (1), a controller (2), a reaction tank (3), a discharge pipe (4) and a feed pipe (6); one end of the base (1) is fixedly mounted to two ends of the controller (2); the top of the base (1) is fixedly connected to the bottom of the reaction tank (3); a heating component (5) is fixedly mounted inside the base (1); one end of the reaction tank (3) is fixedly connected to one end of the feed pipe (6); and the other end of the reaction tank (3) is fixedly connected to one end of the discharge pipe (4); a mixed reaction channel (8) is arranged inside the reaction tank (3); one end of the mixed reaction channel (8) is provided with a straight channel (7); and the other end of the mixed reaction channel (8) is provided with an outflow channel (9); the cross section of the mixed reaction channel (8) is rectangular or circular; the width of the straight channel (7) is 60-600 μm; and the width of the mixed reaction channel (8) is 200-1200 μm.

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