A kind of synthetic method of 3-iminomethyltetrahydrofuran

Abstract

The invention provides a method for preparing 3-iminomethyltetrahydrofuran. 3-formyltetrahydrofuran is used as a raw material, and an amination reaction is performed with ammonia in a microreactor to obtain 3-iminomethyltetrahydrofuran. The specific process is: a solvent is evenly mixed with 3-formyltetrahydrofuran to obtain a 3-formyltetrahydrofuran solution; the 3-formyltetrahydrofuran solution is pumped into a micromixer through a metering pump, and at the same time, ammonia enters the micromixer after passing through a gas flow meter, and after being evenly mixed, enters a microreactor to perform an amination reaction, and the reaction product enters a receiving tank. The method has the advantages of simple operation, safety, and high efficiency, and is suitable for industrial production.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis and relates to a method for synthesizing 3-iminomethyltetrahydrofuran. Technical Background

[0002] Dinotefuran belongs to the third generation of nicotinoid insecticides. It has the characteristics of contact killing, stomach poison, strong root systemicity, high rapid effect, long lasting effect of 4-8 weeks (theoretical lasting effect of 43 days), broad insecticide spectrum, etc. It has excellent control effect on piercing-sucking mouthparts pests and shows high insecticidal activity at very low doses. It is mainly used to control aphids, leafhoppers, planthoppers, thrips, whiteflies and their resistant strains on various crops such as wheat, rice, cotton, vegetables, fruit trees, tobacco leaves, etc. It has a high control effect on coleoptera, diptera, lepidoptera and homoptera pests, and has a high control effect on cockroaches, termites, houseflies and other sanitary pests.

[0003] 3-Iminomethyltetrahydrofuran is an important intermediate for the synthesis of dinotefuran. There are several main methods for its synthesis:

[0004] In patent CN107935970A, anhydrous methanol is added to a reactor, and liquid ammonia and 3-formaldehyde tetrahydrofuran are added in sequence under stirring and cooling, and stirred under nitrogen protection to react to obtain an imine intermediate; the temperature of the reaction system does not exceed 0° C. After the reaction is completed, the temperature is lowered, and ammonia and methanol are recovered by distillation, and the reaction time is relatively long.

[0005] In patent CN109438396A, 3-formaldehyde tetrahydrofuran is used as raw material and water is used as reaction solvent. Under the action of supported bimetallic catalyst, after nitrogen replacement, it reacts with liquid ammonia to obtain an imine intermediate. During the reaction, the catalyst is a supported bimetallic catalyst, and the amount used is 1% to 10% of the weight of 3-formaldehyde tetrahydrofuran. After the reaction is completed, the reaction liquid needs to be distilled (20kpa, kettle temperature 100°C, top temperature 80°C) and filtered to remove the catalyst. The total reaction time is 1-5h, and the reaction temperature is relatively high (50 to 140°C).

[0006] The traditional preparation method of 3-aminomethyltetrahydrofuran is usually an intermittent kettle reaction: add a certain amount of methanol to the reactor, cool it down, pass ammonia, absorb it to a certain concentration, slowly drop 3-formyltetrahydrofuran at low temperature, stir for a certain time after the addition, and then proceed to the subsequent reaction if the reaction is qualified. Since the process of methanol absorbing ammonia is highly exothermic, the traditional kettle reactor needs to strictly control the speed of passing ammonia due to the limited heat exchange area to avoid excessive temperature, ammonia waste and safety hazards; the process of dropping 3-formyltetrahydrofuran is also an exothermic reaction with high energy consumption, and the dropping speed needs to be controlled, which prolongs the dropping reaction time and restricts the production capacity; in addition, the reaction system in the prior art often has the problems of large catalyst usage and long reaction time, and the reaction system with short reaction time has the problem of low product yield.

[0007] The method uses a microreactor as a reaction device, which can effectively avoid the disadvantages of an intermittent reactor. The microreactor can make the gas and the reaction liquid fully contact, increase the heat exchange area, and the actual operation is simple and efficient, and can realize continuous production. Summary of the invention

[0008] The invention provides a safe and efficient synthesis method of 3-imidomethyltetrahydrofuran, which effectively solves the problems of intense heat release, high energy consumption, large gas consumption and great safety hazards in the existing synthesis process of the amination process.

[0009] The reaction formula is as follows:

[0010]

[0011] The technical solution of the present invention is as follows:

[0012] A method for synthesizing 3-iminomethyltetrahydrofuran comprises the following steps:

[0013] a. The solvent and 3-formyltetrahydrofuran are uniformly mixed to obtain a 3-formyltetrahydrofuran solution;

[0014] b. The 3-formyltetrahydrofuran solution is pumped into the micro mixer through a metering pump. Meanwhile, ammonia gas passes through a gas flow meter and enters the micro mixer. After being mixed evenly, the mixture enters the micro reactor to carry out an amination reaction.

[0015] c. The reaction product enters the receiving tank and undergoes subsequent reaction after detection and analysis;

[0016] Furthermore, the solvent used in step a is any one of methanol, ethanol, propanol, isopropanol, water, toluene, xylene, trimethylbenzene, N,N-dimethylformamide, N,N-dimethylacetamide, dichloromethane, dichloroethane, cyclohexane, n-pentane, n-hexane, n-heptane, ethyl acetate, tetrahydrofuran, or a mixture thereof.

[0017] Furthermore, in step a, the mass ratio of 3-formyltetrahydrofuran to the solvent is 1:1 to 20;

[0018] Furthermore, in step a, the mass ratio of 3-formyltetrahydrofuran to the solvent is 1:1 to 8;

[0019] Furthermore, in step a, the mass ratio of 3-formyltetrahydrofuran to the solvent is 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, 1:7, 1:8;

[0020] Furthermore, in step a, the mass ratio of 3-formyltetrahydrofuran to the solvent is 1:2-5;

[0021] Furthermore, in step a, the mass ratio of 3-formyltetrahydrofuran to the solvent is 1:2, 1:3, 1:5;

[0022] Further, in step b, the molar ratio of 3-formyltetrahydrofuran to ammonia is 1:1 to 15;

[0023] Further, in step b, the molar ratio of 3-formyltetrahydrofuran to ammonia is 1:2.5-12;

[0024] Further, in step b, the molar ratio of 3-formyltetrahydrofuran to ammonia is 1:3 to 12;

[0025] Further, in step b, the molar ratio of 3-formyltetrahydrofuran to ammonia is 1:1.05-1.69;

[0026] Further, in step b, the molar ratio of 3-formyltetrahydrofuran to ammonia is 1:1.05, 1:1.08, 1:1.55 or 1:1.69;

[0027] Further, the reaction temperature in step b is 0-50°C;

[0028] Further, the reaction temperature in step b is 0-30°C;

[0029] Further, the reaction temperature in step b is 20-30°C;

[0030] Further, in step b, the reaction temperature is 20°C, 25°C, 28°C or 30°C;

[0031] Further, the reaction temperature in step b is 20°C or 30°C;

[0032] Further, in step b, the pressure range is 0.0-0.5MPa;

[0033] Further, in step b, the pressure range is 0.0-0.5MPa;

[0034] Further, in step b, the pressure range is 0.08MPa, 0.2MPa, 0.25MPa;

[0035] Further, the residence time in step b is 1 to 50 s;

[0036] Furthermore, the residence time in step b is 10 to 50 seconds;

[0037] Furthermore, the residence time in step b is 30 to 50 seconds.

[0038] Further, the residence time in step b is 30s, 40s, 50s;

[0039] The present invention has the following advantages:

[0040] 1) The reaction rate is fast. Due to the full contact between the gas and liquid phases, the mass transfer efficiency is high and the reaction time is significantly shortened;

[0041] 2) Good selectivity, few by-products, extremely small diameter of the pipeline in the microreactor, the reaction raw materials and gas can be fully mixed in the microchannel, greatly improving the mass transfer efficiency, conversion rate and selectivity;

[0042] 3) High safety. The microreactor will not accumulate a large amount of materials, avoiding the temperature jump caused by the violent exothermic reaction, greatly reducing the risk factor;

[0043] 4) Modular application of microreactors can reduce floor space, save costs, and avoid the use of autoclaves;

[0044] 5) No catalyst, through the structural module in the microreactor, the reaction materials are fully mixed and can react quickly without the use of catalyst;

[0045] 6) High yield: Since the reaction materials have a short residence time in the microreactor, side reactions can be avoided, so that the reaction conversion rate is greater than 99% and the product yield reaches more than 98%. DETAILED DESCRIPTION

[0046] In order to make the technical solutions and advantages of the present invention more clearly understood, the present invention is further described in detail below in conjunction with embodiments. It should be understood that the specific embodiments described herein are only used to explain the present invention and are not used to limit the present invention. BRIEF DESCRIPTION OF THE DRAWINGS

[0047] Figure 1 It is a schematic diagram of an apparatus for synthesizing 3-imidomethyltetrahydrofuran in a filled microreactor of the present invention;

[0048] In the figure: 101-raw material storage tank; 102-ammonia storage tank; 103-microreactor; 104-product storage tank; 105-metering pump; 106-gas flow meter; 107-micro mixer; 108-back pressure valve; 109-gas-liquid separation device; 110-pressure regulator.

[0049] Figure 2 The liquid chromatogram of the product obtained in Example 4;

[0050] Figure 3 The liquid chromatogram of the product obtained in Comparative Example 1;

[0051] Figure 4 The liquid chromatogram of the product obtained in Control Example 2.

[0052] Example 1

[0053] A method for synthesizing 3-iminomethyltetrahydrofuran, comprising the following steps:

[0054] Reference Figure 1 The microreactor connection mode is determined, and the heat exchange medium is glycerol. It includes: a raw material storage tank 101; an ammonia storage tank 102; a microreactor 103; a product storage tank 104; a metering pump 105; a gas flow meter 106; a micro mixer 107; a back pressure valve 108; a gas-liquid separation device 109; and a pressure regulator 110.

[0055] The raw material storage tank 101 is connected to the metering pump 105, the ammonia storage tank 102 is connected to the gas flow meter 106, the metering pump 105 and the gas flow meter 106 are connected to the micro mixer 107, the micro mixer 107 is connected to the micro reactor 103, the micro reactor 103 is connected to the back pressure valve 108, the back pressure valve 108 is connected to the gas-liquid separation device 109, the gas-liquid separation device 109 is connected to the pressure regulator 110, and the pressure regulator 110 is connected to the gas flow meter 106.

[0056] 3-Formyltetrahydrofuran (98%, 100g) and 300g methanol were mixed and placed in a raw material storage tank, the temperature control system was turned on to make the microreactor temperature 20°C, and a metering pump was used to enter the micromixer at a flow rate of 1.8mL / min. At the same time, the gas flow meter was adjusted, and ammonia entered the micromixer at a flow rate of 68.7mL / min through a stainless steel high-pressure pipeline, and the pressure was 0.2MPa; after uniform mixing, it entered the microreactor, and the residence time was 50s. The reaction liquid entered the receiving tank after passing through the gas-liquid separation device to obtain 394g of ammonia reaction liquid, with a content of 24.3% (gas phase detection) and a yield of 98.7% (based on 3-formyltetrahydrofuran); the separated ammonia passed through the ammonia recovery pipeline, entered the pressure regulator to adjust the pressure, and then entered the microreactor again through the flow meter to participate in the reaction.

[0057] Example 2

[0058] A method for synthesizing 3-iminomethyltetrahydrofuran, comprising the following steps:

[0059] 3-formyltetrahydrofuran (98%, 120g) and 600g toluene are mixed and placed in a raw material storage tank, the temperature control system is turned on, the temperature of the microreactor is 30°C, and the flow rate of 2.7mL / min is entered into the micromixer through a metering pump. At the same time, the gas flow meter is adjusted, and ammonia enters the micromixer through a stainless steel high-pressure pipeline at a flow rate of 50.4mL / min, and the pressure is 0.25MPa; after uniform mixing, it enters the microreactor, and the residence time is 40s. The reaction liquid enters the receiving tank after the gas-liquid separation device to obtain 612g of ammonia reaction liquid, with a content of 18.9% (gas phase detection) and a yield of 99.4% (based on 3-formyltetrahydrofuran); the separated ammonia passes through the ammonia recovery pipeline, enters the pressure regulator to adjust the pressure, and then enters the microreactor again through the flow meter to participate in the reaction.

[0060] Example 3

[0061] A method for synthesizing 3-iminomethyltetrahydrofuran, comprising the following steps:

[0062] 3-formyltetrahydrofuran solution (98%, 200g) and 400g ethanol were mixed and placed in a raw material storage tank, the temperature control system was turned on to make the microreactor temperature 30°C, and a flow rate of 1.5mL / min was passed through a metering pump to enter the micromixer. At the same time, the gas flow meter was adjusted, and ammonia entered the micromixer through a stainless steel high-pressure pipeline at a flow rate of 30.0mL / min, and the pressure was 0.08MPa; after uniform mixing, it entered the microreactor, and the residence time was 30s. The reaction liquid entered the receiving tank after the gas-liquid separation device to obtain 588g of ammonia reaction liquid, with a content of 31.8% (gas phase detection) and a yield of 96.4% (based on 3-formyltetrahydrofuran); the separated ammonia passed through an ammonia recovery pipeline, entered the pressure regulator to adjust the pressure, and then entered the microreactor again through a flow meter to participate in the reaction.

[0063] Example 4

[0064] A method for synthesizing dinotefuran, comprising the following specific steps:

[0065] 1) 3-formyltetrahydrofuran (98%, 100g) and 200g methanol are mixed and placed in a raw material storage tank, the temperature control system is turned on, the temperature of the microreactor is set to 20°C, and the metering pump enters the micromixer at a flow rate of 1.0mL / min. At the same time, the gas flow meter is adjusted, and ammonia enters the micromixer at a flow rate of 20.0mL / min through a stainless steel high-pressure pipeline, and the pressure is 0.1MPa; after uniform mixing, it enters the microreactor, and the residence time is 50s. The reaction liquid enters the receiving tank after passing through the gas-liquid separation device to obtain 295g of ammonia reaction liquid, with a content of 32.5% (gas phase detection) and a yield of 98.8% (based on 3-formyltetrahydrofuran); the separated ammonia passes through the ammonia recovery pipeline, enters the pressure regulator to adjust the pressure, and then enters the microreactor again through the flow meter to participate in the reaction.

[0066] 2) Take the above 3-aminomethyltetrahydrofuran solvent (32.5%, 200g) and place it in a high-pressure reactor, replace the system with 0.3MPa nitrogen for 3 times, and then replace the system with 0.3MPa hydrogen for 3 times, flush with hydrogen to 1.0MPa, slowly heat up to 60°C, keep the temperature and pressure for 3h, close the air inlet valve, and cool to room temperature. Open the reactor, take a sample and analyze it in the central control. Take out the reaction material, heat it up to remove the solvent, and distill it to obtain 65.8g of 3-aminomethyltetrahydrofuran, with a content of 99.0% (gas phase detection) and a yield of 98.2% (based on 3-aminomethyltetrahydrofuran).

[0067] 3) 40g of sodium chloride, 7g of sodium hydroxide, 150g of water, and 41g of N,O-dimethyl-N'-nitroisourea (99.0%) were placed in a reaction bottle, cooled to -10°C, and 30g of 3-aminomethyltetrahydrofuran (99.0%) was slowly added dropwise. After the addition was completed, the temperature was slowly raised to room temperature, and the reaction was kept warm for 4h. The sampling was qualified. The reaction solution was cooled to 0°C, filtered, rinsed, and dried to obtain 59.8g of dinotefuran product, with a content of 94.3% (liquid phase detection) and a yield of 95.0% (based on 3-aminomethyltetrahydrofuran).

[0068] Comparative Example 1

[0069] A method for synthesizing dinotefuran, comprising the following specific steps:

[0070] 1) Add 300g of methanol to a batch reactor, cool to 0°C under nitrogen protection, add 135g of liquid ammonia and 100g (98%) of 3-formyltetrahydrofuran, control the system temperature not to exceed 0°C, continue to keep warm and react for 1h after the addition is completed, and take samples to pass the control. 430g of 3-iminomethyltetrahydrofuran reaction liquid is obtained, with a content of 17.6% (gas phase detection) and a yield of 78.0%.

[0071] 2) Take the above 3-aminomethyltetrahydrofuran solvent (17.6%, 250g) and place it in a high-pressure reactor, replace the system with 0.3MPa nitrogen for 3 times, and then replace the system with 0.3MPa hydrogen for 3 times, flush with hydrogen to 1.0MPa, slowly heat up to 60°C, keep the temperature and pressure for 3h, close the air inlet valve, and cool to room temperature. Open the reactor, take a sample and analyze it in the central control. Take out the reaction material, heat it up to remove the solvent, and distill it to obtain 42.3g of 3-aminomethyltetrahydrofuran, with a content of 91.5% (gas phase detection) and a yield of 86.2% (based on 3-aminomethyltetrahydrofuran).

[0072] 3) 40g of sodium chloride, 7g of sodium hydroxide, 150g of water, and 41g of N,O-dimethyl-N'-nitroisourea (99.0%) were placed in a reaction bottle, cooled to -10°C, and 30g of 3-aminomethyltetrahydrofuran (91.5%) was slowly added dropwise. After the addition was completed, the temperature was slowly raised to room temperature, and the reaction was kept warm for 4h. The sampling was qualified. The reaction solution was cooled to 0°C, filtered, rinsed, and dried to obtain 53.5g of dinotefuran product, with a content of 87.0% (liquid phase detection) and a yield of 84.8% (based on 3-aminomethyltetrahydrofuran).

[0073] Comparative Example 2

[0074] A method for synthesizing dinotefuran, comprising the following specific steps:

[0075] 1) Into an autoclave, 100 g of water, 5 g of 0.5% Sn-3% Rh / Al2O3 catalyst, and 100 g (98%) of 3-formyltetrahydrofuran were added. After the autoclave was sealed, the system was replaced with nitrogen three times, and then 50 g of liquid ammonia was introduced. The temperature was raised to 80°C and the reaction was kept warm for 3 hours. After sampling and central control, 230 g of 3-iminomethyltetrahydrofuran reaction liquid was obtained, with a content of 36.0% (gas phase detection) and a yield of 85.3%.

[0076] 2) Take the above 3-aminomethyltetrahydrofuran solution (36.0%, 150g) and place it in a high-pressure reactor, replace the system with 0.3MPa nitrogen for 3 times, and then replace the system with 0.3MPa hydrogen for 3 times, flush with hydrogen to 1.0MPa, slowly heat up to 60°C, keep the temperature and pressure for 3h, close the air inlet valve, and cool to room temperature. Open the reactor, take a sample and analyze it in the central control. Take out the reaction material, heat it up to remove the solvent, and distill it to obtain 48.24g of 3-aminomethyltetrahydrofuran, with a content of 90.8% (gas phase detection) and a yield of 79.5% (based on 3-aminomethyltetrahydrofuran).

[0077] 3) 40g of sodium chloride, 7g of sodium hydroxide, 150g of water, and 41g of N,O-dimethyl-N'-nitroisourea (99.0%) were placed in a reaction bottle, cooled to -10°C, and 30g of 3-aminomethyltetrahydrofuran (90.8%) was slowly added dropwise. After the addition was completed, the temperature was slowly raised to room temperature, and the reaction was kept warm for 4h. The sampling was qualified. The reaction solution was cooled to 0°C, filtered, rinsed, and dried to obtain 51.9g of dinotefuran product, with a content of 91.4% (liquid phase detection) and a yield of 87.1% (based on 3-aminomethyltetrahydrofuran).

[0078] The above embodiments are only preferred technical solutions of the present invention and should not be regarded as limitations of the present invention. The protection scope of the present invention should be the technical solutions recorded in the claims, including equivalent replacement solutions of the technical features in the technical solutions recorded in the claims, that is, equivalent replacement improvements within this scope are also within the protection scope of the present invention.

Claims

1. A method for synthesizing 3-iminomethyltetrahydrofuran, characterized in that: The steps include: a. The solvent and 3-formyltetrahydrofuran are uniformly mixed to obtain a 3-formyltetrahydrofuran solution, wherein the solvent used is any one of methanol, ethanol, and toluene; the mass ratio of 3-formyltetrahydrofuran to the solvent is 1:2-5; b. The 3-formyltetrahydrofuran solution is pumped into the micromixer through a metering pump. At the same time, ammonia gas passes through a gas flow meter and enters the micromixer. After being uniformly mixed, it enters the microreactor for amination reaction. The reaction temperature is 20-30° C., the reaction pressure is 0.08-0.25 MPa, the residence time is 30-50 s, and the molar ratio of 3-formyltetrahydrofuran to ammonia gas is 1:1.05-1.69; c. The reaction product enters a receiving tank to obtain 3-iminomethyltetrahydrofuran.

2. The synthetic method of 3-iminomethyltetrahydrofuran according to claim 1, characterized in that: In step a, the mass ratio of 3-formyltetrahydrofuran to the solvent is 1:2, 1:3 or 1:

5.

3. The synthetic method of 3-iminomethyltetrahydrofuran according to claim 1, characterized in that: In step b, the molar ratio of 3-formyltetrahydrofuran to ammonia is 1:1.05, 1:1.08, 1:1.55, and 1:1.

69.

4. The synthetic method of 3-iminomethyltetrahydrofuran according to claim 1, characterized in that: The reaction temperature in step b is 20°C or 30°C.

5. The synthetic method of 3-iminomethyltetrahydrofuran according to claim 1, characterized in that: The pressure in step b is 0.08Mpa, 0.2Mpa, and 0.25MPa.

6. The synthetic method of 3-iminomethyltetrahydrofuran according to claim 1, characterized in that: The residence time in step b is 30s, 40s, and 50s.

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