CN111072518B - Continuous synthesis method of ethoxymethylene malononitrile - Google Patents
Continuous synthesis method of ethoxymethylene malononitrile Download PDFInfo
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Abstract
The invention provides a continuous synthesis method of ethoxymethylene malononitrile. The method comprises the following steps: continuously introducing malononitrile, triethyl orthoformate and acetic anhydride into continuous reaction equipment for substitution reaction to obtain ethoxymethylene malononitrile, and continuously discharging the generated ethoxymethylene malononitrile in the substitution reaction process; wherein the molar ratio of the malononitrile to the triethyl orthoformate to the acetic anhydride is 1 (0.9-6.0) to 2.0-6.0. By adopting the continuous reaction equipment, the invention greatly reduces the material quantity participating in the reaction in unit time, reduces the high-temperature dangerous area and greatly reduces the safety risk. And the raw materials can be instantly heated to the reaction temperature through the continuous reactor, so that the decomposition of the raw materials caused by a long-time heating process is avoided, and the yield is obviously improved. Moreover, the reaction process of the invention does not need two types of toxic solvents such as toluene.
Description
Technical Field
The invention relates to the technical field of organic synthesis, and particularly relates to a continuous synthesis method of ethoxymethylene malononitrile.
Background
The ethoxymethylene malononitrile is white to off-white crystalline powder, is insoluble in water, is soluble in organic solvents such as methanol, ethanol and the like, has a melting point of 65-67 ℃ and a boiling point of 160 ℃ (12 mmHg), is commonly used for preparing intermediates of industrial chemicals and medicinal chemicals, and is used as an intermediate for preparing milrinone. Therefore, the ethoxymethylene malononitrile has extremely wide field and development prospect, and the development of a high-benefit and low-cost ethoxymethylene malononitrile synthesis process is of great significance.
Currently, the preparation method of ethoxymethylene malononitrile comprises the following steps: refluxing triethyl orthoformate and malononitrile in the presence of an organic solvent and a catalyst until the reaction is complete, wherein the organic solvent is a high-boiling-point toxic solvent such as toluene. Toluene belongs to the two classes of solvents that are restricted for use according to the international harmonization for human medicine (ICH) regulations.
Liu Qiming et al (Liu Qiming, suyuyong, chenbang silver, zhang Han Nu Ping, synthesis and structural identification of phosphodiesterase inhibitor Millinon [ J ]. Huazhong university of science and technology (medical edition), 2005, 34 (1): 74-75) disclose a preparation method of ethoxy methylene malononitrile, this method uses poisonous toluene as solvent in a large number, the zinc chloride of catalyst used is insoluble in organic solvent (toluene) and difficult to fully contact with reactant, lead to unsatisfactory catalytic effect, influence reaction speed and reaction effect, the yield is only 79% (counted with malononitrile), so there are disadvantages such as unfavorable to environment protection, high production cost, difficult solvent recovery, low yield.
Chinese patent (CN 102584626) provides a method for preparing ethoxymethylene malononitrile, in which malononitrile and triethyl orthoformate are used as initial raw materials, zinc chloride is used as a catalyst, and the zinc chloride used as the catalyst is insoluble in an organic solvent and difficult to fully contact with a reaction substance, so that the catalytic effect is not ideal, the reaction speed and the reaction effect are influenced, the amount of triethyl used as the raw material is large, the yield is only 85% (based on malononitrile), and the method still has the problems of low yield, high cost, slow reaction speed and low production efficiency.
In addition, foreign patents (WO 2014/2111, 2014) provide a novel method for preparing ethoxymethylene malononitrile, acetic anhydride is used as a reagent for reaction, the reaction temperature is 110-140 ℃, but the safe operation temperature suggested by the process is T <107 ℃ (Td 24), the Stoessel grade of the reaction is 5, the danger grade is high, the traditional kettle type reactor is used for scale-up production, the safety risk is high, and the scale-up production cannot be carried out.
For the reasons, the method for producing the ethoxymethylene malononitrile has the advantages of safer operation, less pollution and high yield.
Disclosure of Invention
The invention mainly aims to provide a continuous synthesis method of ethoxymethylene malononitrile, which aims to solve the problems of low yield, environmental pollution caused by toxic solvents and poor safety in the preparation of ethoxymethylene malononitrile in the prior art.
In order to accomplish the above objects, according to one aspect of the present invention, there is provided a continuous synthesis method of ethoxymethylenemalononitrile, which includes the steps of: continuously introducing malononitrile, triethyl orthoformate and acetic anhydride into continuous reaction equipment for substitution reaction to obtain ethoxymethylene malononitrile, and continuously discharging the generated ethoxymethylene malononitrile in the substitution reaction process; wherein the molar ratio of the malononitrile to the triethyl orthoformate to the acetic anhydride is 1 (0.9-6.0) to 2.0-6.0.
Furthermore, the molar ratio of the malononitrile to the triethyl orthoformate to the acetic anhydride is 1 (1.1-1.5) to 2.1-2.5.
Furthermore, the reaction temperature of the substitution reaction is 110-150 ℃, and the reaction pressure is 0.3-10 MPa.
Furthermore, the reaction temperature of the substitution reaction is 110-120 ℃, and the reaction pressure is 0.3-10 MPa.
Further, the substitution reaction is carried out in the absence of a solvent or in the presence of a solvent.
Further, and when a solvent is employed, the solvent is selected from one or more of ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, benzene, toluene, xylene, acetone, acetonitrile, methanol, ethanol, isopropanol, ethylene glycol.
Further, in the process of the substitution reaction, the retention time of the malononitrile, the triethyl orthoformate and the acetic anhydride in the continuous reaction equipment is 30-400 min.
Further, in the process of the substitution reaction, the retention time of the malononitrile, the triethyl orthoformate and the acetic anhydride in the continuous reaction equipment is 90-120 min.
Further, the continuous reaction apparatus is a tubular continuous reactor or a columnar continuous reactor.
Further, during the substitution reaction, malononitrile, triethyl orthoformate, acetic anhydride and optionally a solvent are pumped into the continuous reaction apparatus by a pump, and the total pumping rate is 20ml/min to 5L/min.
The invention realizes the continuous production of the ethoxy methylene malononitrile by adopting continuous reaction equipment and the continuous substitution reaction of the malononitrile, the triethyl orthoformate and the acetic anhydride. Compared with the traditional kettle type reaction, the material quantity participating in the reaction in unit time is greatly reduced, the high-temperature dangerous area is reduced, and the safety risk is greatly reduced. And the raw materials can be instantly heated to the reaction temperature through the continuous reactor, so that the decomposition of the raw materials caused by a long-time heating process is avoided, and the yield is obviously improved. Moreover, the reaction process of the invention does not need two types of toxic solvents such as toluene. In addition, the safety risk of the process can be obviously reduced due to the adoption of the continuous process and the continuous reaction equipment, and the large-scale production can be realized.
Detailed Description
It should be noted that, in the present application, the embodiments and features of the embodiments 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 section, the prior art for preparing ethoxymethylenemalononitrile has the problems of low yield, environmental pollution caused by toxic solvents and poor safety.
In order to solve the above problems, the present invention provides a continuous synthesis method of ethoxymethylenemalononitrile, which comprises the steps of: continuously introducing malononitrile, triethyl orthoformate and acetic anhydride into continuous reaction equipment for substitution reaction to obtain ethoxymethylene malononitrile, and continuously discharging the generated ethoxymethylene malononitrile in the substitution reaction process; wherein the molar ratio of the malononitrile to the triethyl orthoformate to the acetic anhydride is 1 (0.9-6.0) to 2.0-6.0.
The continuous production of the ethoxymethylene malononitrile is realized by adopting continuous reaction equipment and carrying out continuous substitution reaction on the malononitrile, the triethyl orthoformate and the acetic anhydride. Compared with the traditional kettle type reaction, the material quantity participating in the reaction in unit time is greatly reduced, the high-temperature dangerous area is reduced, and the safety risk is greatly reduced. And the raw materials can be instantly heated to the reaction temperature through the continuous reactor, so that the raw materials are prevented from being decomposed in the long-time heating process, and the yield is remarkably improved (the highest yield can reach more than 98.5%). Moreover, the reaction process of the invention does not need two types of toxic solvents such as toluene. In addition, the safety risk of the process can be obviously reduced due to the adoption of the continuous process and the continuous reaction equipment, and the large-scale production can be realized.
In addition to the beneficial effects, compared with the traditional kettle type production process, the invention also has the advantages of low cost, small amount of three wastes and the like, and the reaction time is greatly shortened due to continuous reaction, so that the production efficiency is obviously improved. Meanwhile, the post-treatment is simple, and the product purity is higher and even can reach more than 99.5%.
In order to further improve the reaction efficiency and the product yield, in a preferred embodiment, the molar ratio of malononitrile, triethyl orthoformate and acetic anhydride is 1 (1.1-1.5) to (2.1-2.5).
As mentioned above, the raw materials can be instantly heated to the reaction temperature by the continuous reactor, so that the decomposition of the raw materials caused by a long-time temperature rise process is avoided, and the yield is remarkably improved. In order to further improve the reaction efficiency and the product yield and avoid excessive temperature causing raw materials, in a preferred embodiment, the reaction temperature of the substitution reaction is 110-150 ℃, and the reaction pressure is 0.3-10 MPa. More preferably, the reaction temperature of the substitution reaction is 110 to 120 ℃ and the reaction pressure is 0.3 to 10MPa.
Because of the high safety of the continuous substitution reaction, the malononitrile, triethyl orthoformate and acetic anhydride can be reacted directly in the absence of a solvent. Of course, the reaction can also be carried out in the presence of solvents which are not toxic to the second class. Preferably and when a solvent is employed, the solvent is selected from one or more of ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, benzene, toluene, xylene, acetone, acetonitrile, methanol, ethanol, isopropanol, ethylene glycol. Preferably, the amount of solvent used is from 1 to 50mg/g, relative to malononitrile.
In a preferred embodiment, the residence time of malononitrile, triethyl orthoformate and acetic anhydride in the continuous reaction apparatus during the substitution reaction is between 30 and 400min, more preferably between 90 and 120min. Under the retention time, the substitution reaction is more sufficient, which is beneficial to further improving the reaction yield.
In a preferred embodiment, the malononitrile, triethyl orthoformate, acetic anhydride and optionally solvent are pumped into the continuous reaction apparatus during the substitution reaction by means of a pump, and the total pumping rate is from 20mL/min to 5L/min, preferably from 100 to 300mL/min. It should be noted that the above-mentioned pumping speed refers to the total pumping speed of all the raw materials, and those skilled in the art can convert the feeding speed of each raw material according to the required dosage ratio of each raw material, and will not be described herein again.
The specific liquid inlet mode can be various: mixing malononitrile and acetic anhydride to form a raw material A under the solvent-free condition, taking triethyl orthoformate as a raw material B, and respectively pumping the raw material A and the raw material B into a continuous reactor through a pump A and a pump B to react; in the second mode, when a solvent participates, malononitrile and an acetic anhydride compound are dissolved in one part of the solvent to form a raw material A, and triethyl orthoformate is dissolved in the other part of the solvent to form a raw material B; then the raw material A and the raw material B are simultaneously pumped into the continuous reactor by a pump A and a pump B respectively to carry out reaction.
The above-mentioned continuous reactor may preferably be a tubular continuous reactor or a columnar continuous reactor. More preferably, the continuous reactor is a coil type reactor, and the special structure of the coil inside the reactor is helpful for increasing the reaction effect. More preferably, the continuous reactor comprises a coil pipe, a heat exchange device, a temperature detection device, a pressure detection device, a liquid flow controller, an online PAT device and an automatic control system; the coil is used for providing a reaction site; the heat exchange equipment is used for adjusting the temperature inside the coil; the temperature detection equipment is used for monitoring the reaction temperature in the coil; the pressure detection equipment is used for monitoring the reaction pressure in the coil pipe; the liquid flow controller is connected between the pump and the feed inlet of the coil pipe and is used for adjusting and controlling the feed amount; the online PAT equipment is used for detecting the composition of a product in the coil; the automatic control system is electrically connected with the pump, the liquid flow controller, the heat exchange equipment, the temperature detection equipment, the pressure detection equipment and the online PAT equipment. By adopting an automatic control system, the relevant parameters of the reaction such as temperature, pressure, flow rate and the like can be accurately controlled and fed back in real time.
After the ethoxymethylenemalononitrile formed has been continuously discharged, the above synthesis process further comprises a step of purifying it, preferably the purification step comprises: and (3) concentrating the discharged product in vacuum, then dropwise adding n-heptane into the system to separate out the ethoxymethylene malononitrile, and filtering to obtain the ethoxymethylene malononitrile product.
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 present application as claimed.
Example 1
The feeding amount is 1.0kg, malononitrile (1.0kg, 15.14mol) and acetic anhydride (3.25kg, 31.79mol) are uniformly mixed at room temperature, and the mixture is marked as a material A; triethyl orthoformate (2.47kg, 16.65mol) was recorded as material B. The pump a speed was: 248g/min, 157g/min of pump B, respectively pumping the material A and the material B into a continuous pipeline reactor (with the volume of 50L) by using pumps, controlling the temperature at 120 ℃, keeping the pressure at the outlet of the continuous reactor at 0.3-0.5 MPa, keeping the residence time at 100min, sampling the outlet, and carrying out GC analysis, wherein the residual of the raw materials is 0.0-0.5%. And (3) concentrating the system flowing out of the continuous reactor to 6V under vacuum, controlling the temperature to be 20-30 ℃, dropwise adding 4V n-heptane into the system, and separating out a large amount of solid from the system after the dropwise adding is finished. Filtering, drying the solid to obtain 1.83kg of product ethoxymethylene malononitrile, wherein the GC purity is as follows: 99.7% and a yield of 98.69%.
Example 2
Pump A system was malononitrile (100g, 1.51mol) + acetic anhydride (325g, 3.18mol), pump B was triethyl orthoformate (247g, 1.67mol), pump A speed was: 24.8g/min, and the speed of the pump B is 15.7g/min. Simultaneously starting a pump A and a pump B to pump two raw materials into a continuous reactor (with the volume of 5L), controlling the temperature at 130 ℃, keeping the pressure at the outlet of the continuous reactor at 0.3-0.5 MPa, keeping the retention time at 100min, sampling at the outlet for GC analysis, keeping the raw material residue at 0.0-0.5%, concentrating the effluent system to 6V, dropwise adding 4V n-heptane for crystallization, filtering to obtain 165.0g of ethoxy methylene malononitrile, and obtaining the GC purity: 97.2% and yield 79.8%.
Differences from example 1: the reaction temperature was 130 ℃.
Example 3
Pump A system was malononitrile (100g, 1.51mol) + acetic anhydride (325g, 3.18mol) + ethanol (100 ml), pump B was triethyl orthoformate (247g, 1.67mol) + ethanol (100 ml), pump A speed was: 24.8g/min, the speed of a pump B is 15.7g/min, the pump A and the pump B are started simultaneously to pump the two raw materials into a continuous reactor (with the volume of 5L), the temperature is controlled to be 120 ℃, the pressure of an outlet of the continuous reactor is 0.3-0.5 MPa, the retention time is 100min, a sample is taken from the outlet for GC analysis, the residual raw material is 0.0-0.5%, an effluent system is concentrated and concentrated to 6V, 4V n-heptane is dripped for crystallization, and the product, namely, ethoxymethylene malononitrile, is filtered, the purity of the ethoxymethylene malononitrile is 175.0g, and the GC purity: 75.3%, yield 66.15%.
Differences from example 1: ethanol was used as the solvent.
Example 4
Pump A system was malononitrile (100g, 1.51mol) + acetic anhydride (618.14g, 6.05mol), pump B was triethyl orthoformate (201.9g, 1.36mol), and pump A speed was: 24.8g/min, the speed of a pump B is 15.7g/min, the pump A and the pump B are started simultaneously to pump two raw materials into a continuous reactor (with the volume of 5L), the temperature is controlled to be 120 ℃, the pressure of an outlet of the continuous reactor is 0.3-0.5 MPa, the retention time is 100min, a sample is taken from the outlet for GC analysis, the residual raw material is 1.6-2.5%, an effluent system is concentrated and concentrated to 6V, 4V n-heptane is dripped for crystallization, and the product, namely, the ethoxymethylene malononitrile, is 173.0g, the gas phase purity: 91.1% and yield 83.7%.
Differences from example 1: and (3) by mol ratio of malononitrile: triethyl orthoformate: acetic anhydride =1:0.9:4.0
Example 5
Pump A system was malononitrile (100g, 1.51mol) + acetic anhydride (386.3 g, 3.78mol), pump B was triethyl orthoformate (336.5g, 2.27mol), pump A speed was: 24.8g/min, and the speed of the pump B is 15.7g/min. Simultaneously starting a pump A and a pump B to pump two raw materials into a continuous reactor (with the volume of 5L), controlling the temperature at 120 ℃, keeping the pressure at the outlet of the continuous reactor at 0.3-0.5 MPa, keeping the retention time at 100min, sampling at the outlet for GC analysis, keeping the raw material residue at 0.0-0.5%, concentrating the effluent system to 6V, dropwise adding 4V n-heptane for crystallization, filtering to obtain a product, namely, the ethoxymethylene malononitrile 181.0g, and obtaining the GC purity: 99.6% and a yield of 98.52%.
Differences from example 1: and (3) by mol ratio of malononitrile: triethyl orthoformate: acetic anhydride =1:1.5:2.5.
example 6
Pump A system was malononitrile (100g, 1.51mol) + acetic anhydride (3091g, 3.03mol), pump B was triethyl orthoformate (1350g, 9.08mol), pump A speed was: 24.8g/min, and the speed of the pump B is 15.7g/min. Simultaneously starting a pump A and a pump B to pump two raw materials into a continuous reactor (with the volume of 5L), controlling the temperature at 120 ℃, keeping the pressure at the outlet of the continuous reactor at 0.3-0.5 MPa, keeping the retention time at 100min, sampling at the outlet for GC analysis, keeping the raw material residue at 0.0-0.5%, concentrating the effluent system to 6V, dropwise adding 4V n-heptane for crystallization, filtering to obtain 141.0g of ethoxy methylene malononitrile product, and obtaining the GC purity: 91.2% and yield 69.6%.
Differences from example 1: and (2) malononitrile by mol ratio: triethyl orthoformate: acetic anhydride =1:6.0:2.0.
example 7
Pump A system was malononitrile (100g, 1.51mol) + acetic anhydride (3091g, 3.03mol), pump B was triethyl orthoformate (1350g, 9.08mol), pump A speed was: 24.8g/min, and the speed of the pump B is 15.7g/min. Simultaneously starting a pump A and a pump B to pump two raw materials into a continuous reactor (with the volume of 5L), controlling the temperature at 120 ℃, keeping the pressure at the outlet of the continuous reactor at 0.3-0.5 MPa, keeping the retention time at 100min, sampling at the outlet, carrying out GC analysis, keeping the raw material residue at 0.0-0.5%, concentrating the effluent system to 6V, dropwise adding 4V n-heptane for crystallization, filtering to obtain a product, namely, the ethoxymethylene malononitrile, of 140.1g, and carrying out GC purity: 91.6% and a yield of 68.7%.
Differences from example 1: and (3) by mol ratio of malononitrile: triethyl orthoformate: acetic anhydride =1:0.9:6.0.
example 8
Pump A system was malononitrile (100g, 1.51mol) + acetic anhydride (325g, 3.18mol), pump B was triethyl orthoformate (247g, 1.67mol), pump A speed was: 24.8g/min, the speed of a pump B is 15.7g/min, the pump A and the pump B are started simultaneously to pump the two raw materials into a continuous reactor (with the volume of 2.5L), the temperature is controlled to be 120 ℃, the pressure of an outlet of the continuous reactor is 0.3-0.5 MPa, the retention time is 45min, the outlet samples for GC analysis, the residual raw materials are 16-17%, an effluent system is concentrated and concentrated to 6V, 4V n-heptane is dripped for crystallization, and the product, namely, the ethoxymethylene malononitrile, is filtered, and 143.1g, the gas phase purity: 72.3%, yield 67.96%.
Differences from example 1: the retention time was 45min.
Example 9
Pump A system is malononitrile (100g, 1.51mol) + acetic anhydride (325g, 3.18mol), pump B is triethyl orthoformate (247g, 1.67mol), pump A speed is: 24.8g/min, the speed of the pump B is 15.7g/min, the pump A and the pump B are started simultaneously to pump two raw materials into a continuous reactor (with the volume of 5L), the temperature is controlled at 120 ℃, the pressure at the outlet of the continuous reactor is 0.3-0.5 MPa, the retention time is 90min, the outlet is sampled and analyzed by GC, the residual raw materials are 0.0-0.5%, the effluent system is concentrated and concentrated to 6V, 4V n-heptane is dripped to crystallize, the crystals are filtered, the solid is dried to obtain 182.3g of the product ethoxymethylenemalononitrile, the GC purity: 99.5% and a yield of 98.12%.
Differences from example 1: the retention time was 90min.
Example 10
Pump A system is malononitrile (100g, 1.51mol) + acetic anhydride (325g, 3.18mol), pump B is triethyl orthoformate (247g, 1.67mol), pump A speed is: 24.8g/min, the speed of the pump B is 15.7g/min, the pump A and the pump B are started simultaneously to pump two raw materials into a continuous reactor (with the volume of 5L), the temperature is controlled at 120 ℃, the pressure at the outlet of the continuous reactor is 0.3-0.5 MPa, the retention time is 120min, the outlet is sampled and analyzed by GC, the residual raw materials are 0.0-0.5%, the effluent system is concentrated and concentrated to 6V, 4V n-heptane is dripped to carry out crystallization, the filtration and the solid drying are carried out to obtain 182.7g of the product ethoxymethylenemalononitrile, the GC purity: 99.5% and yield 98.33%.
Differences from example 1: the retention time was 120min.
Example 11
Pump A system is malononitrile (100g, 1.51mol) + acetic anhydride (325g, 3.18mol), pump B is triethyl orthoformate (247g, 1.67mol), pump A speed is: 24.8g/min, the speed of the pump B is 15.7g/min, the pump A and the pump B are started simultaneously to pump the two raw materials into a continuous reactor (with the volume of 2.5L), the temperature is controlled to be 120 ℃, the pressure of an outlet of the continuous reactor is 0.3-0.5 MPa, the retention time is 30min, the outlet is sampled and analyzed by GC, the residual raw materials are 19-22%, an effluent system is concentrated and concentrated to 6V, 4V n-heptane is dripped to perform crystallization, and the product, namely, 139.4g of ethoxymethylenemalononitrile, is obtained after filtration, the gas phase purity: 70.8%, yield 53.39%.
Differences from example 1: the retention time was 30min.
Example 12
Pump A system is malononitrile (100g, 1.51mol) + acetic anhydride (325g, 3.18mol), pump B is triethyl orthoformate (247g, 1.67mol), pump A speed is: 24.8g/min, the speed of a pump B is 15.7g/min, the pump A and the pump B are started simultaneously to pump two raw materials into a continuous reactor (with the volume of 5L), the temperature is controlled to be 120 ℃, the pressure of an outlet of the continuous reactor is 0.3-0.5 MPa, the retention time is 400min, the outlet is sampled and analyzed by GC, the residual amount of the raw materials is 0-0.5%, an effluent system is concentrated and concentrated to 6V, 4V n-heptane is dripped to perform crystallization, and the product, namely, 180.0g of ethoxymethylenemalononitrile, is obtained after filtration, and the gas phase purity: 61.2%, yield 59.59%.
Differences from example 1: the retention time was 400min.
Example 13
Pump A system was malononitrile (100g, 1.51mol) + acetic anhydride (325g, 3.18mol), pump B was triethyl orthoformate (247g, 1.67mol), pump A speed was: 24.8g/min, the speed of a pump B is 15.7g/min, the pump A and the pump B are started simultaneously to pump two raw materials into a continuous reactor (with the volume of 5L), the temperature is controlled at 110 ℃, the pressure at the outlet of the continuous reactor is 10MPa, the retention time is 100min, the sampling of the outlet is performed by GC analysis, the residual of the raw materials is 0.0-0.5%, the effluent system is concentrated and concentrated to 6V, 4V n-heptane is dripped to perform crystallization, the filtration is performed, the solid is dried to obtain a product, namely, the ethoxymethylene malononitrile 180.4g, the GC purity is as follows: 98.9% and a yield of 96.51%.
Differences from example 1: the reaction temperature is 110 ℃ and the pressure is 10MPa.
Example 14
Pump A system was malononitrile (100g, 1.51mol) + acetic anhydride (325g, 3.18mol), pump B was triethyl orthoformate (247g, 1.67mol), pump A speed was: 24.8g/min, the speed of the pump B is 15.7g/min, the pump A and the pump B are started simultaneously to pump the two raw materials into a continuous reactor (with the volume of 5L), the temperature is controlled at 150 ℃, the pressure at the outlet of the continuous reactor is 0.9MPa, the residence time is 100min, the outlet is sampled and analyzed by GC, the residual raw materials are 0.0-0.5%, the effluent system is concentrated to 6V, 4V n-heptane is dripped to perform crystallization, and the product, namely, the ethoxymethylene malononitrile, is 185.6g, the gas phase purity: 59.4% and yield 59.64%.
Differences from example 1: the reaction temperature is 150 ℃ and the pressure is 0.9MPa.
It should be noted that, in the above embodiment, the continuous reaction equipment continuously operates for 24x7 h, and the reaction columns and the like are equipped with corresponding standby equipment and parts, so that the equipment can be replaced on line without stopping, and the full continuous reaction without interruption in the whole process can be achieved.
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.
Claims (8)
1. A continuous synthesis method of ethoxymethylene malononitrile is characterized by comprising the following steps: continuously introducing malononitrile, triethyl orthoformate and acetic anhydride into continuous reaction equipment for substitution reaction to obtain the ethoxymethylene malononitrile, and continuously discharging the generated ethoxymethylene malononitrile during the substitution reaction; wherein the molar ratio of the malononitrile to the triethyl orthoformate to the acetic anhydride is 1 (0.9-6.0) to 2.0-6.0; the reaction temperature of the substitution reaction is 110-150 ℃, and the reaction pressure is 0.3-10 MPa; the residence time of the malononitrile, the triethyl orthoformate and the acetic anhydride in the continuous reaction equipment is 30-400 min.
2. The continuous synthesis method of ethoxymethylenemalononitrile according to claim 1, wherein the molar ratio of the malononitrile, the triethyl orthoformate and the acetic anhydride is 1 (1.1-1.5) to (2.1-2.5).
3. The continuous synthesis method of ethoxymethylenemalononitrile according to claim 1, wherein the reaction temperature of the substitution reaction is 110 to 120 ℃, and the reaction pressure is 0.3 to 10MPa.
4. The continuous synthesis process of ethoxymethylenemalononitrile according to any one of claims 1 to 3, wherein the substitution reaction is carried out without or with a solvent.
5. The continuous process for the synthesis of ethoxymethylenemalononitrile according to claim 4, wherein the solvent is selected from one or more of ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, 1, 4-dioxane, ethylene glycol dimethyl ether, diethylene glycol dimethyl ether, benzene, toluene, xylene, acetone, acetonitrile, methanol, ethanol, isopropanol, ethylene glycol when used.
6. The continuous synthesis method of ethoxymethylenemalononitrile according to claim 5, wherein the residence time of the malononitrile, the triethyl orthoformate and the acetic anhydride in the continuous reaction apparatus during the substitution reaction is 90 to 120min.
7. The continuous synthesis process of ethoxymethylenemalononitrile according to any one of claims 1 to 3, wherein the continuous reaction apparatus is a tubular continuous reactor or a column continuous reactor.
8. The continuous synthesis process of ethoxymethylenemalononitrile according to claim 4, wherein during the substitution reaction, the malononitrile, triethyl orthoformate, the acetic anhydride and optionally the solvent are pumped into the continuous reaction apparatus by a pump, and the total pumping speed is 20ml/min to 5L/min.
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| US4468353A (en) * | 1976-08-10 | 1984-08-28 | Dynamit Nobel Ag | Method of preparing alkoxymethylene compounds |
| CN102584626A (en) * | 2011-12-21 | 2012-07-18 | 蚌埠丰原医药科技发展有限公司 | Synthetic method of (ethoxymethylene)-malononitrile |
| WO2014002111A1 (en) * | 2012-06-26 | 2014-01-03 | Rallis India Limited | Process of preparation of azimsulfuron |
| CN103664695A (en) * | 2013-12-18 | 2014-03-26 | 南京易亨制药有限公司 | Preparation method and refining method of ethoxymethylenemalononitrile |
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| US4468353A (en) * | 1976-08-10 | 1984-08-28 | Dynamit Nobel Ag | Method of preparing alkoxymethylene compounds |
| CN102584626A (en) * | 2011-12-21 | 2012-07-18 | 蚌埠丰原医药科技发展有限公司 | Synthetic method of (ethoxymethylene)-malononitrile |
| WO2014002111A1 (en) * | 2012-06-26 | 2014-01-03 | Rallis India Limited | Process of preparation of azimsulfuron |
| CN103664695A (en) * | 2013-12-18 | 2014-03-26 | 南京易亨制药有限公司 | Preparation method and refining method of ethoxymethylenemalononitrile |
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