CN114181186A - Preparation method of difluoro piperonyl - Google Patents
Preparation method of difluoro piperonyl Download PDFInfo
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- CN114181186A CN114181186A CN202111125434.0A CN202111125434A CN114181186A CN 114181186 A CN114181186 A CN 114181186A CN 202111125434 A CN202111125434 A CN 202111125434A CN 114181186 A CN114181186 A CN 114181186A
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Abstract
A preparation method of difluoro piperonyl rings comprises the following steps: the method comprises the following steps: introducing chlorine and phosphorus trichloride at a temperature of 0-80 ℃ according to a ratio of 1: 3-9, refluxing for 1-4 hours after the preparation of the phosphorus pentachloride is finished so as to ensure that chlorine and phosphorus trichloride completely react and prevent the phosphorus pentachloride from hanging on the wall; step two: adding piperonyl butoxide into phosphorus pentachloride dropwise for 1-24h, wherein the molar ratio of the phosphorus pentachloride to the piperonyl butoxide is 1: 0.5-1.5; after the dripping is finished, refluxing for 1-24h at the temperature of 50-100 ℃; removing the phosphorus trichloride solvent to obtain dichloro-piperonyl chloride; step three: the molar ratio of the dichloro-pepper ring to the hydrogen fluoride is 1.8-8: 1, dropwise adding hydrogen fluoride into the dichloro-piperonyl chloride for 0.5-24h, reacting at the reaction temperature of 5-40 ℃ for 0.5-24h after the dropwise addition is finished, adjusting the pH value to 7-14, and distilling with water vapor to obtain the dichloro-piperonyl chloride. The method is simple, convenient and feasible, has high yield and high purity, has low cost and mild reaction conditions, and is suitable for industrial mass production.
Description
Technical Field
The invention belongs to the field of preparation of difluoro piperonyl rings, and particularly relates to a preparation method of difluoro piperonyl rings.
Background
Fludioxonil is a novel contact-killing protective bactericide, has a unique action mechanism, and inhibits the growth of pathogenic bacteria mycelia by inhibiting glucose phosphorylation related transfer, thereby finally causing the death of pathogenic bacteria.
Difluoro piperonyl (full name: 2, 2-difluoro-1, 3-benzodioxole) is colorless liquid with boiling point of 129 deg.C
The temperature of-130 ℃ is a key intermediate for synthesizing the agricultural fungicide fludioxonil. Yan Duanmin et al (world pesticides, 2010, 32(3), 36-38) describe the synthesis of fludioxonil.
The invention aims to provide a novel preparation method of difluoro piperonyl rings, which can be used for simply, conveniently and easily obtaining the difluoro piperonyl rings with high yield and high purity, has low cost and mild reaction conditions and is suitable for industrial mass production.
The literature reports that the synthesis methods of the difluoro pepper ring include the following methods:
in Chinese patent CN103497180B, Wangliening et al reported that pyrocatechol and dibromodifluoromethane react by taking potassium carbonate as an acid-binding agent and an autoclave under the condition of taking NMP as a solvent to obtain difluoro pepper rings, wherein the yield is about 80%. The method has the advantages of simple reaction, but has the problems of low yield, expensive price of the raw material of the dibromodifluoromethane, high requirement on equipment, high requirement on high pressure kettle, rectification of the product and the like. Additionally, both NMP and potassium carbonate are used to enter the wastewater creating a large volume of wastewater and difficult to dispose of. This solution is difficult to implement in industrial production.
The reaction of catechol with dichlorodifluoromethane to obtain difluoro piperonyl rings is reported in Chinese patent CN105237509A by Bukangming et al. The reaction of catechol and dichloromethane requires harsh reaction conditions to prepare the piperonyl butoxide. According to common chemical theory common knowledge and practical experience of the inventor in preparing the piperonyl and the 3-aldehyde piperonyl, the reaction is difficult to carry out, and toluene is used as a solvent, the boiling point of the toluene is close to that of difluoro piperonyl, and the rectification and the complete separation of the two are difficult.
Kumarasmary, Radha et al, in world patent WO2020070759, report that piperonyl rings undergo radical substitution reaction by introducing chlorine gas under the solvent (such as trifluorotoluene, 3, 4-dichlorotrifluorotoluene) or solvent-free conditions using light or a radical initiator to obtain dichloropiperonyl rings, which are then reacted with hydrogen fluoride to obtain difluoropiperonyl rings. A similar synthesis was also reported in Chua Kongrong et al in Chinese patent CN 102153430B. A similar process is also reported by Biasetton, Silvia and Marinello, Franco in european patent EP 1502908. The method uses illumination or a free radical initiator to initiate chlorine chlorination, so that chlorination on a benzene ring is easy to generate, particularly under the condition of containing a small amount of metal ions, methylene chlorination is completed, and the benzene ring is easier to chlorinate due to slight excess of chlorine. In addition, the dichloro-pepper nucleus is easy to decompose when meeting water, and the conventional industrial chlorine gas is difficult to ensure that the moisture content is low. The use of trifluorotoluene or 3, 4-dichlorotrifluorotoluene makes product separation difficult requiring rectification equipment.
Lutomski, Kathryn a.; duggan, Angelina j.; engel, John F. reported in U.S. patent US 4895871 that dichloro-piperonyl rings were prepared by reacting piperonyl rings with phosphorus pentachloride. The method is difficult to be applied in industry, the phosphorus pentachloride is solid which is easy to absorb moisture, the feeding is inconvenient, the phosphorus pentachloride and the pepper rings are heated and reacted together, the reaction speed is high when the temperature is high, a large amount of hydrogen chloride is generated, and safety accidents are easy to cause. Grossenbacher, Rene; rauber, Peter; suess, Hans in Switzerland patent CH 676119A 5 reported that dichloro-piperonyl ring was obtained in 90% yield by chlorination with chlorine gas using phosphorus trichloride as a solvent. The method is difficult to avoid side reaction on a benzene ring on chlorine, needs additional purification steps to purify, reduces the product yield, and has high boiling point of the dichloro pepper ring and great purification difficulty.
Fluorination of dichloro-piperonyl rings using pyridine hydrogen fluoride salts to give difluoro-piperonyl rings is reported by Janin, Robert and Saint-Jalmes, Laurent in U.S. Pat. No. 6316636, 13Nov 2001. Janin, Robert and Saint-Jalmes, Laurent in European patent EP729930 reports fluorination of dichloro-piperonyl ring using triethylamine hydrofluoride to give difluoro-piperonyl ring. Pyridine or triethylamine hydrogen fluoride salt is used for fluorination, the reaction effect is good, but the two fluorination reagents are difficult to separate from the difluoro piperonyl, and are difficult to apply mechanically, and the three-waste treatment difficulty is obviously increased due to the introduction of the pyridine or the triethylamine. Fluorination of the dichloro-piperonyl ring with hydrogen fluoride to give the difluoro-piperonyl ring was reported by Schnalke, Karl Erwin et al in European patent EP590459 in 93% yield. The method has high equipment requirement, high reaction pressure and high operation requirement. In addition, the product post-treatment does not have a step of removing acidic substances (hydrogen fluoride and hydrogen chloride), and a small amount of acidic substances can be remained in the difluoro piperonyl ring to be unfavorable for the next reaction using the butyl lithium.
Sunfuqiang et al reported in Chinese patent CN106810530B that the piperonyl butoxide uses phosphorus oxychloride as a solvent, uses phosphorus pentachloride for chlorination, and performs rectification under reduced pressure to obtain by-products of phosphorus trichloride and phosphorus oxychloride as a solvent to obtain dichloro piperonyl butoxide, and at 0-5 ℃ and under the vacuum degree of-0.1 to-0.09 MPa, hydrogen fluoride liquid is dripped for fluorination reaction, and after the product is washed with alkali, the difluoro piperonyl butoxide is obtained by distillation, with high yield and high purity. This patent is most similar to the present invention's scheme for making difluoropiperonyl rings, in that dichloropiperonyl rings are first fluorinated with hydrogen fluoride to form monochlorofluorinated piperonyl rings, which solidify at low temperatures (about 6 ℃ C. freezing point, observed experimentally and not reported in the literature), and in the case described in this patent, stirring locking occurs. Apart from the authenticity, the patent of Sunfu and the like has the problems that phosphorus oxychloride and phosphorus trichloride need to be rectified and removed, the equipment requirement is high, the operation is complicated, and the dropwise addition of hydrogen fluoride under the vacuum condition can greatly consume hydrogen fluoride and cause environmental pollution.
Disclosure of Invention
The invention provides a preparation method of difluoro piperonyl butoxide, which is used for overcoming the defects in the prior art.
The invention is realized by the following technical scheme:
a preparation method of difluoro piperonyl rings comprises the following steps:
the method comprises the following steps: introducing chlorine and phosphorus trichloride at a temperature of 0-80 ℃ according to a ratio of 1: 3-9, refluxing for 1-4 hours after the preparation of the phosphorus pentachloride is finished so as to ensure that chlorine and phosphorus trichloride completely react and prevent the phosphorus pentachloride from hanging on the wall;
step two: adding pepper rings into phosphorus pentachloride dropwise for 1-24h, wherein the molar ratio of the phosphorus pentachloride to the pepper rings is 1: 0.5-1.5; after the dripping is finished, refluxing for 1-24h at the temperature of 50-100 ℃; removing the phosphorus trichloride solvent to obtain dichloro-piperonyl chloride;
step three: the molar ratio of the dichloro-pepper ring to the hydrogen fluoride is 1.8-8: 1, dropwise adding hydrogen fluoride into the dichloro-piperonyl chloride for 0.5-24h, reacting at the reaction temperature of 5-40 ℃ for 0.5-24h after dropwise adding, adjusting the pH value to 7-14, and distilling with water vapor to obtain the dichloro-piperonyl chloride.
In the preparation method of the difluoro pepper ring, the chlorine gas introducing temperature in the first step is 30-65 ℃.
In the preparation method of difluoro piperonyl rings, the dripping time of the piperonyl rings in the second step is 3-6 h.
The preparation method of difluoro piperonyl rings is characterized in that the reflux reaction temperature in the second step is 60-80 ℃; the reaction time is 1-2 h.
In the preparation method of difluoro piperonyl rings, the phosphorus trichloride removing mode in the second step is atmospheric distillation and/or reduced pressure distillation and/or atmospheric distillation and/or reduced pressure distillation.
In the preparation method of the difluoro piperonyl rings, the phosphorus trichloride removal mode in the second step is that the phosphorus trichloride is distilled at normal pressure and then is completely removed by distillation at reduced pressure.
The preparation method of difluoro piperonyl ring as described above, the molar ratio of dichloro piperonyl ring and hydrogen fluoride in the step III is 2.2-3: 1.
in the preparation method of difluoro piperonyl rings, the dripping time of the dichloro piperonyl rings in the step III is 3-6h, and the dichloro piperonyl rings are reacted for 0.5-3h at the reaction temperature of 5-15 ℃ after the dripping is finished.
The preparation method of difluoro piperonyl ring as described above, the pH is adjusted to 8-10 in the third step.
In the preparation method of difluoro piperonyl rings, after the reaction in the third step is finished, the reaction can be washed with water for layering and then the pH value can be adjusted, and the pH value can also be directly adjusted.
The preparation method of the difluoro piperonyl ring is described.
The invention has the advantages that:
1. the method is simple, convenient and feasible, has high yield and high purity, has low cost and mild reaction conditions, and is suitable for industrial mass production.
2. Phosphorus trichloride is used as a solvent, chlorine and phosphorus trichloride react to generate phosphorus pentachloride, phosphorus pentachloride and piperonyl to generate phosphorus trichloride, and the phosphorus trichloride can be recycled and is actually mainly consumed as chlorine. The loss rate of phosphorus trichloride in the experiment for trial use in a workshop is about 5 percent. Phosphorus trichloride is used as a solvent to prepare phosphorus pentachloride, and the anhydrous state of a reaction system can be ensured, so that the hydrolysis of the dichloro-piperonyl ring is avoided.
3. Because the phosphorus pentachloride is prepared in advance, free chlorine does not exist in the reaction process, and the chlorination on a benzene ring is avoided. The piperonyl butoxide is added into the reaction system in a dropwise manner, so that the safety risk of large-scale release of hydrogen chloride in a short time is avoided.
4. After the preparation of the dichloro-piperonyl chloride is finished, the phosphorus trichloride is removed by distillation under normal pressure and reduced pressure, and the phosphorus trichloride can be directly applied to the next batch for preparing the phosphorus pentachloride, so that complicated equipment such as rectification is avoided.
5. The reaction temperature of the fluorination is controlled to avoid the problem of difficult stirring in the intermediate process.
6. The post-treatment of the difluoro pepper ring adopts steam distillation, which is easy to ensure the product quality (the gas-phase normalized content of each batch is more than or equal to 99.9 percent), also ensures the product neutrality, adopts treatment methods such as membrane treatment or cyclohexane azeotropic dehydration and the like to ensure the low water content, and can use the next butyl lithium reaction. The treatment method is not reported in documents, and the equipment requirement is obviously lower than that of the prior art, and rectification is not needed. The total yield of the two steps can reach more than 90 percent, and if the introduction of water vapor and the controlled volatilization loss of the difluoro piperonyl rings can be strictly avoided in the reaction process, the total yield of the two steps can reach 95 percent.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings needed to be used in the description of the embodiments or the prior art will be briefly described below, and it is obvious that the drawings described below are some embodiments of the present invention, and those skilled in the art can also obtain other drawings according to the drawings without creative efforts.
FIG. 1 is a detection map of example 1 of the present invention;
FIG. 2 is a detection map of example 2 of the present invention.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention clearer, the technical solutions in the embodiments of the present invention will be clearly and completely described below with reference to the drawings in the embodiments of the present invention, and it is obvious that the described embodiments are some, but not all, embodiments of the present invention. All other embodiments, which can be obtained by a person skilled in the art without any inventive step based on the embodiments of the present invention, are within the scope of the present invention.
Example 1
And (5) checking the 5000L chlorination kettle and accessory equipment thereof, and confirming that the chlorination kettle is dry and clean and the valve is in a closed state. (accumulated liquid cannot exist in the kettle, and phosphorus trichloride can release heat in a large amount when meeting water and can spray materials). Opening a vacuum valve of the chlorination kettle, vacuumizing to-0.08 MPa, opening a nitrogen valve, filling nitrogen to replace air in the chlorination kettle and the pipeline of the accessory facilities until the system pressure is normal pressure, and repeating the steps twice. And opening an emptying valve of the chlorination kettle, opening a phosphorus trichloride feeding valve, and adding 4332Kg of phosphorus trichloride into the reaction kettle by using a diaphragm pump. The method is characterized in that a chlorination kettle jacket is opened in advance, the temperature of the chlorination kettle is reduced to 10-15 ℃, the temperature is controlled to be less than 40 ℃, 760Kg of chlorine gas is introduced, and the highest pressure of a buffer kettle is not more than 2 Kg. After chlorine gas is introduced, the cooling oil is closed, hot oil in the chlorination kettle is started, a tail gas absorption system is started, the temperature is adjusted to 80-85 ℃, and the temperature is kept for 1 hour to ensure that the phosphorus pentachloride is dissolved. Controlling the temperature to be 75-80 ℃, slowly dripping 642Kg of piperonyl butoxide (the temperature is controlled not to exceed 80 ℃, otherwise, the pepper is likely to be washed) for 3-4 hours. The reaction was incubated for 1 hour. Distilling phosphorus trichloride at normal pressure, collecting phosphorus trichloride to a normal pressure receiving kettle, and recovering phosphorus trichloride under reduced pressure when the temperature reaches 100 ℃. When the reduced pressure distillation is carried out, observation sight glasses are required, when yellow distillate is generated, the vacuum degree is about-0.094 MPa, the kettle temperature is 110 ℃, the heating is stopped, the temperature is reduced to 30-40 ℃, the vacuum is broken by nitrogen, and the remainder is the crude product of the dichloro-piperonyl cyclocarya for standby. The individual batches weighed approximately 960 Kg. The 2000L fluorination kettle and its accessories were checked to confirm that all were normal. Adding the crude product of the dichloro-piperonyl cycloacetate into a fluorination kettle, and starting a stirring and cooling system. 260Kg of hydrogen fluoride was pumped into a hydrogen fluoride storage tank, and the hydrogen fluoride was pumped into a hydrogen fluoride head tank. And (3) starting a tail gas absorption device, controlling the temperature to be 5-15 ℃, closing an emptying valve, dropwise adding metered hydrogen fluoride, and finishing dropwise adding within 4 hours. The pressure in the kettle was observed, the pressure was controlled to be less than 2kg and 2kg, the dropwise addition was stopped, the pressure was maintained for 5 minutes, and the pressure was released. And (5) releasing the pressure to normal pressure, closing the air release, and continuing to dropwise add. After the addition of hydrogen fluoride was completed, the mixture was stirred at 10 to 15 ℃ for 2 hours. After the reaction is finished, the materials are transferred to a neutralization kettle, 30 percent sodium hydroxide is used for adjusting the pH value to be 9-10, water is added and transferred to a steam distillation kettle for distillation, the distillate is discharged at the temperature of 92 ℃, the distillate is kept stand for layering, the lower layer white transparent liquid is difluoro pepper ring, the weight is about 745Kg, the yield of the two steps is about 90 percent, and the gas phase normalization content is 99.9 percent.
Example 2
And (5) checking the 5000L chlorination kettle and accessory equipment thereof, and confirming that the chlorination kettle is dry and clean and the valve is in a closed state. (accumulated liquid cannot exist in the kettle, and phosphorus trichloride can release heat in a large amount when meeting water and can spray materials). Opening a vacuum valve of the chlorination kettle, vacuumizing to-0.08 MPa, opening a nitrogen valve, filling nitrogen to replace air in the chlorination kettle and the pipeline of the accessory facilities until the system pressure is normal pressure, and repeating the steps twice. And opening an emptying valve of the chlorination kettle, opening a phosphorus trichloride feeding valve, and adding 4332Kg of phosphorus trichloride into the reaction kettle by using a diaphragm pump. The method is characterized in that a chlorination kettle jacket is opened in advance, the temperature of the chlorination kettle is reduced to 10-15 ℃, the temperature is controlled to be less than 40 ℃, 760Kg of chlorine gas is introduced, and the highest pressure of a buffer kettle is not more than 2 Kg. After chlorine gas is introduced, the cooling oil is closed, hot oil in the chlorination kettle is started, a tail gas absorption system is started, the temperature is adjusted to 80-85 ℃, and the temperature is kept for 1 hour to ensure that the phosphorus pentachloride is dissolved. Controlling the temperature to be 75-80 ℃, slowly dripping 642Kg of piperonyl butoxide (the temperature is controlled not to exceed 80 ℃, otherwise, the pepper is likely to be washed) for 3-4 hours. The reaction was incubated for 1 hour. Distilling phosphorus trichloride at normal pressure, collecting phosphorus trichloride to a normal pressure receiving kettle, and recovering phosphorus trichloride under reduced pressure when the temperature reaches 100 ℃. When the reduced pressure distillation is carried out, observation sight glasses are required, when yellow distillate is generated, the vacuum degree is about-0.094 MPa, the kettle temperature is 110 ℃, the heating is stopped, the temperature is reduced to 30-40 ℃, the vacuum is broken by nitrogen, and the remainder is the crude product of the dichloro-piperonyl cyclocarya for standby. The single batch weighed about 1010 Kg. The 2000L fluorination kettle and its accessories were checked to confirm that all were normal. Adding the crude product of the dichloro-piperonyl cycloacetate into a fluorination kettle, and starting a stirring and cooling system. 290Kg of hydrogen fluoride was introduced into a hydrogen fluoride storage tank, and the whole amount of hydrogen fluoride was introduced into a hydrogen fluoride head tank. And (3) starting a tail gas absorption device, controlling the temperature to be 5-15 ℃, closing an emptying valve, dropwise adding metered hydrogen fluoride, and finishing dropwise adding within 4 hours. The pressure in the kettle was observed, the pressure was controlled to be less than 2kg and 2kg, the dropwise addition was stopped, the pressure was maintained for 5 minutes, and the pressure was released. And (5) releasing the pressure to normal pressure, closing the air release, and continuing to dropwise add. After the addition of hydrogen fluoride was completed, the mixture was stirred at 10 to 15 ℃ for 2 hours. After the reaction is finished, transferring the materials to a neutralization kettle, adding water, stirring and layering, removing water from the upper layer, adjusting the pH of the organic layer at the lower layer to be 8-9 by using 30% sodium hydroxide, adding water, transferring to a steam distillation kettle for distillation, discharging fractions at the temperature of 92 ℃, standing and layering the distillate, wherein the white transparent liquid at the lower layer is difluoro piperonyl, the weight is about 740Kg, the yield of the two steps is about 89%, and the gas phase normalization content is 99.9%.
Example 3
And (5) checking the 5000L chlorination kettle and accessory equipment thereof, and confirming that the chlorination kettle is dry and clean and the valve is in a closed state. (accumulated liquid cannot exist in the kettle, and phosphorus trichloride can release heat in a large amount when meeting water and can spray materials). Opening a vacuum valve of the chlorination kettle, vacuumizing to-0.08 MPa, opening a nitrogen valve, filling nitrogen to replace air in the chlorination kettle and the pipeline of the accessory facilities until the system pressure is normal pressure, and repeating the steps twice. And opening an emptying valve of the chlorination kettle, opening a phosphorus trichloride feeding valve, and adding 4332Kg of phosphorus trichloride into the reaction kettle by using a diaphragm pump. The method comprises the steps of pre-opening a jacket of a chlorination kettle, cooling the kettle to 10-15 ℃, controlling the temperature to be less than 60-70 ℃, introducing 760Kg of chlorine gas, and ensuring that the highest pressure of a buffer kettle is not more than 2 Kg. After chlorine gas is introduced, the cooling oil is closed, hot oil in the chlorination kettle is started, a tail gas absorption system is started, the temperature is adjusted to 80-85 ℃, and the temperature is kept for 1 hour to ensure that the phosphorus pentachloride is dissolved. Controlling the temperature to be 75-80 ℃, slowly dripping 642Kg of piperonyl butoxide (the temperature is controlled not to exceed 80 ℃, otherwise, the pepper is likely to be washed) for 3-4 hours. The reaction was incubated for 1 hour. Distilling phosphorus trichloride under normal pressure, collecting phosphorus trichloride to a normal pressure receiving kettle, and recovering phosphorus trichloride under reduced pressure when the temperature reaches 100 ℃. When the distillation is carried out under reduced pressure, observing a sight glass, when yellow distillate is generated, the vacuum degree is about-0.094 MPa, the kettle temperature is 110 ℃, stopping heating, cooling to 30-40 ℃, breaking the vacuum by nitrogen, and obtaining the residual crude product of the dichloro-piperonyl cyclocarya for later use. The single batch weighed approximately 990 Kg. The 2000L fluorination kettle and its accessories were checked to confirm that all were normal. Adding the crude product of the dichloro-piperonyl cycloacetate into a fluorination kettle, and starting a stirring and cooling system. 250Kg of hydrogen fluoride was pumped into a hydrogen fluoride storage tank, and the hydrogen fluoride was pumped into a hydrogen fluoride head tank. And (3) starting a tail gas absorption device, controlling the temperature to be 5-15 ℃, closing an emptying valve, dropwise adding metered hydrogen fluoride, and finishing dropwise adding within 4 hours. The pressure in the kettle was observed, the pressure was controlled to be less than 2kg and 2kg, the dropwise addition was stopped, the pressure was maintained for 5 minutes, and the pressure was released. And (5) releasing the pressure to normal pressure, closing the air release, and continuing to dropwise add. After the addition of hydrogen fluoride was completed, the mixture was stirred at 10 to 15 ℃ for 2 hours. After the reaction is finished, transferring the materials to a neutralization kettle, adding water, stirring and layering, removing water from the upper layer, adjusting the pH of the organic layer at the lower layer to be 8-9 by using 30% sodium hydroxide, adding water, transferring to a steam distillation kettle for distillation, discharging fractions at the temperature of 92 ℃, standing and layering the distillate, wherein the white transparent liquid at the lower layer is difluoro piperonyl, the weight is about 680Kg, the yield of the two steps is about 82%, and the gas phase normalization content is 99.9%.
Example 4
A1000 mL four-necked flask equipped with a stirrer, a thermometer and a reflux condenser was examined to confirm that all the components were normal. 867.6g of phosphorus trichloride were added to the reaction flask and the chlorine was started at an initial temperature of 20 ℃. 152.6g (2.13mol) of chlorine gas is introduced for 3 hours, and the temperature is controlled to be 20-40 ℃ in the process of introducing the chlorine gas. The mixture was heated to reflux for 1 hour, and the phosphorus pentachloride on the reaction flask was refluxed. The temperature is reduced to 65 ℃, 127g (1.03mol) of piperonyl butoxide is dripped, the temperature is controlled to be 65-70 ℃, and the dripping is finished within about 1 hour. After the dropwise addition, the reflux reaction is carried out for 1 hour under the condition of heat preservation. And (3) starting to distill phosphorus trichloride at normal pressure, distilling until the temperature in a reaction bottle rises to 100 ℃, and carrying out gas-phase controlled reaction. And if the reaction is finished, the phosphorus trichloride is steamed under reduced pressure. If the raw materials are left, adding phosphorus pentachloride to complete the reaction. Maintaining vacuum at-0.08 Mpa, increasing internal temperature to 140 deg.C, returning top temperature from 70 deg.C to 50 deg.C, stopping distillation, cooling, weighing, analyzing, charging nitrogen, and storing under sealed condition. 181.5g of crude dichloro-piperonyl cycloate is finally obtained, the purity of the gas phase is 98.0 percent, the yield is 90 percent, the crude dichloro-piperonyl cycloate is yellow liquid, and the boiling point is reported to be 110 ℃/25 mmHg.
A300 mL self-made plastic experimental device provided with a magnetic stirring device, an electronic thermometer, a circulating refrigeration system and a tail gas absorption device is checked to confirm that all the devices are normal. 181.5g of the dichloro-pepper ring is added into the device, and a stirring and circulating cooling system is started to cool the mixture to 5 ℃. Keeping the temperature at 5-10 ℃, beginning to drop 84g of anhydrous hydrogen fluoride by a plastic dropper, controlling the temperature at 10-15 ℃ for 1 hour after 5 hours of dropping. And (5) controlling in a middle way, and finishing the reaction. Separating, adding 100mL of water into the lower organic phase, and then dropwise adding 10% sodium hydroxide aqueous solution to adjust the pH to 10-12. The mixture is directly subjected to steam distillation, and distillate is obtained at the top temperature of 92 ℃. The distillate was allowed to stand overnight and subjected to liquid separation to obtain 136g of difluoro piperonyl cycloacetate, the yield was about 92.5%, the gas phase purity was 99.9%, the water content was about 0.17%, and the total yield in the two steps was about 83%. The difluoro piperonyl rings are colorless liquids with boiling points of 129-130 ℃. The freezing point is about 6 ℃ (not accurately determined and not reported in the literature). The water content can reach below 100ppm through membrane treatment or azeotropic dehydration of cyclohexane.
Example 5
A1000 mL four-necked flask equipped with a stirrer, a thermometer and a reflux condenser was examined to confirm that all the components were normal. 867.6g of phosphorus trichloride were added to the reaction flask and the chlorine was started at an initial temperature of 0 ℃. 150g (2.1mol) of chlorine gas is introduced for 3 hours, and the temperature is controlled to be 10-30 ℃ in the process of introducing the chlorine gas. The mixture was heated to reflux for 1 hour, and the phosphorus pentachloride on the reaction flask was refluxed. The temperature is reduced to 65 ℃, 127g (1.03mol) of piperonyl butoxide is dripped, the temperature is controlled to be 65-70 ℃, and the dripping is finished within about 1 hour. After the dropwise addition, the reflux reaction is carried out for 1 hour under the condition of heat preservation. And (3) distilling phosphorus trichloride at normal pressure until the temperature in a reaction bottle rises to 100 ℃, and carrying out gas-phase medium-control reaction. And if the reaction is finished, beginning to evaporate the phosphorus trichloride under reduced pressure. If the raw materials are left, adding phosphorus pentachloride to complete the reaction. Maintaining vacuum degree at-0.08 Mpa, increasing internal temperature to 140 deg.C, lowering top temperature from 70 deg.C to 50 deg.C, stopping distillation, cooling, weighing, analyzing, introducing nitrogen gas, and sealing. 184g of crude dichloro-piperonyl cycloate with a gas phase purity of 98.0% was obtained.
A300 mL self-made plastic experimental device provided with a magnetic stirring device, an electronic thermometer, a circulating refrigeration system and a tail gas absorption device is checked to confirm that all the devices are normal. 184g of the above-mentioned dichloro-pepper ring was added to the apparatus, and the stirring and circulating cooling system was started to cool to 5 ℃. Keeping the temperature at 5-10 ℃, beginning to drop 65g of anhydrous hydrogen fluoride by a plastic dropper, controlling the temperature at 10-15 ℃ for 1 hour after the dropping is finished for 4 hours. And (5) controlling, and finishing the reaction. Separating, adding 100mL of water into the lower organic phase, and then dropwise adding 10% sodium hydroxide aqueous solution to adjust the pH to 10-12. The mixture is directly subjected to steam distillation, and distillate is obtained at the top temperature of 92 ℃. The distillate was allowed to stand overnight and separated to obtain 126g of difluoro piperonyl rings, the yield in the two steps was about 76.5%, and the purity in the gas phase was 99.9%.
Example 6
A1000 mL four-necked flask equipped with a stirrer, a thermometer and a reflux condenser was examined to confirm that all the components were normal. 867.6g of phosphorus trichloride were added to the reaction flask and the chlorine was started at an initial temperature of 0 ℃. 148g (2.06mol) of chlorine gas is introduced for 3 hours, and the temperature is controlled to be 40-60 ℃ in the process of introducing the chlorine gas. The mixture was heated to reflux for 1 hour, and the phosphorus pentachloride on the reaction flask was refluxed. The temperature is reduced to 65 ℃, 127g (1.03mol) of piperonyl butoxide is dripped, the temperature is controlled to be 65-70 ℃, and the dripping is finished within about 1 hour. After the dropwise addition, the reflux reaction is carried out for 1 hour under the condition of heat preservation. And (3) distilling phosphorus trichloride at normal pressure until the temperature in a reaction bottle rises to 100 ℃, and carrying out gas-phase medium-control reaction. And if the reaction is finished, starting to reduce the pressure to evaporate the phosphorus trichloride. If the raw materials are left, adding phosphorus pentachloride to complete the reaction. Maintaining vacuum degree at-0.08 Mpa, increasing internal temperature to 140 deg.C, lowering top temperature from 70 deg.C to 50 deg.C, stopping distillation, cooling, weighing, analyzing, charging nitrogen, and storing under sealed condition. 182g of crude dichloro-piperonyl cycloate with the gas phase purity of 98.0 percent is finally obtained.
A300 mL self-made plastic experimental device provided with a magnetic stirring device, an electronic thermometer, a circulating refrigeration system and a tail gas absorption device is checked to confirm that all the devices are normal. 182g of the dichloro-pepper ring is added into the device, and the stirring and circulating cooling system is started to cool to 5 ℃. Keeping the temperature at 10-15 ℃, beginning to drop about 70g of anhydrous hydrogen fluoride by a plastic dropper, controlling the temperature at 20-25 ℃ for 1 hour after dropping for 3 hours. And (5) controlling, and finishing the reaction. Separating, adding 100mL of water into the lower organic phase, and then dropwise adding 10% sodium hydroxide aqueous solution to adjust the pH to 10-12. The mixture is directly subjected to steam distillation, and distillate is obtained at the top temperature of 92 ℃. The distillate was allowed to stand overnight and separated to give 118.5g of difluoro-piperonyl cycloacetate, the yield in the two steps was about 72%, and the purity in the gas phase was 99.9%.
Finally, it should be noted that: the above examples are only used to illustrate the technical solution of the present invention, but not to limit it; although the present invention has been described in detail with reference to the foregoing embodiments, it will be understood by those of ordinary skill in the art that: the technical solutions described in the foregoing embodiments may still be modified, or some technical features may be equivalently replaced; and such modifications or substitutions do not depart from the spirit and scope of the corresponding technical solutions of the embodiments of the present invention.
Claims (10)
1. A preparation method of difluoro piperonyl rings is characterized by comprising the following steps: the method comprises the following steps:
the method comprises the following steps: introducing chlorine and phosphorus trichloride at a temperature of 0-80 ℃ according to a ratio of 1: 3-9, refluxing for 1-4 hours after the preparation of the phosphorus pentachloride is finished so as to ensure that chlorine and phosphorus trichloride completely react and prevent the phosphorus pentachloride from hanging on the wall;
step two: adding piperonyl butoxide into phosphorus pentachloride dropwise for 1-24h, wherein the molar ratio of the phosphorus pentachloride to the piperonyl butoxide is 1: 0.5-1.5; after the dripping is finished, refluxing for 1-24h at the temperature of 50-100 ℃; removing the phosphorus trichloride solvent to obtain dichloro-piperonyl chloride;
step three: the molar ratio of the dichloro-pepper ring to the hydrogen fluoride is 1.8-8: 1, dropwise adding hydrogen fluoride into the dichloro-piperonyl chloride for 0.5-24h, reacting at the reaction temperature of 5-40 ℃ for 0.5-24h after the dropwise addition is finished, adjusting the pH value to 7-14, and distilling with water vapor to obtain the dichloro-piperonyl chloride.
2. The method for preparing difluoro piperonyl rings according to claim 1, wherein: in the first step, the chlorine gas is introduced at the temperature of 30-65 ℃.
3. The method for preparing difluoro piperonyl rings according to claim 1, wherein: the dripping time of the piperonyl butoxide in the second step is 3-6 h.
4. The method for preparing difluoro piperonyl rings according to claim 1, wherein: the reflux reaction temperature in the second step is 60-80 ℃; the reaction time is 1-2 h.
5. The method for preparing difluoro piperonyl rings according to claim 1, wherein: and the phosphorus trichloride removing mode in the second step is atmospheric distillation and/or reduced pressure distillation and/or atmospheric rectification and/or reduced pressure rectification.
6. The method for preparing difluoro piperonyl rings according to claim 5, wherein: and in the second step, the phosphorus trichloride removal mode is that the phosphorus trichloride is distilled at normal pressure and then is completely removed by reduced pressure distillation.
7. The method for preparing difluoro piperonyl rings according to claim 1, wherein: in the third step, the molar ratio of the dichloro-piperonyl ring to the hydrogen fluoride is 2.2-3: 1.
8. the method for preparing difluoro piperonyl rings according to claim 1, wherein: the dropping time of the dichloro-piperonyl chloride in the third step is 3-6h, and the dichloro-piperonyl chloride reacts for 0.5-3h at the reaction temperature of 5-15 ℃ after the dropping is finished.
9. The method for preparing difluoro piperonyl rings according to claim 1, wherein: and in the third step, the pH value is adjusted to 8-10.
10. The method for preparing difluoro piperonyl rings according to claim 1, wherein: after the reaction in the third step is finished, the pH can be adjusted after water washing and layering, or the pH can be directly adjusted.
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