CN111470995B - High-safety synthesis method of p-chloro-o-nitroacetoacetanilide - Google Patents
High-safety synthesis method of p-chloro-o-nitroacetoacetanilide Download PDFInfo
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Abstract
The invention belongs to the field of chemical synthesis, and relates to a high-safety synthesis method of p-chloro-o-nitroacetoacetanilide, which utilizes methyl acetoacetate, ethyl acetoacetate or tert-butyl acetoacetate to replace diketene in the prior art and redefines the dosage and reaction conditions of reactants, thereby overcoming the defects of adopting diketene as a raw material, obtaining p-chloro-o-nitroacetoacetanilide products with the highest content of more than 98 percent, having the highest yield of more than 96 percent, being applicable after three-stage condensation of waste gas, being applicable to a solvent, recovering low-content p-chloro-o-nitroacetoacetanilide from crystallization filtrate through concentration and secondary crystallization, further reducing solid waste and lowering production cost.
Description
Technical Field
The invention relates to the field of chemical synthesis, and in particular provides a high-safety synthesis method of p-chloro-o-nitroacetoacetanilide.
Background
Quizalofop-p-ethyl, chemical name (R) -2- [4- (6-chloroquinoxalin-2-yloxy) phenoxy ] propionic acid ethyl ester, named quizalofop-p-ethyl, is an improved product after removal of inactive optical isomer in the process of synthesizing quizalofop-p-ethyl.
The action mechanism and the weed killing spectrum are similar to those of gramineae, and the herbicide is absorbed by weed stems and leaves, is conducted upwards and downwards in a plant body, accumulated at the top and in the middle, inhibits the synthesis of cell fatty acid and causes the necrosis of weeds. Quizalofop-p-ethyl is a novel dry land stem and leaf treating agent with high selectivity, has high selectivity between gramineous weeds and dicotyledonous crops, and has good control effect on gramineous weeds in broadleaf crop fields.
The p-chloro-o-nitroacetanilide is an intermediate for synthesizing quizalofop-p-ethyl, the main raw materials for synthesizing the p-chloro-o-nitroacetanilide at present are p-chloro-o-nitroaniline and diketene, and the reaction equation is as follows:
in the reaction for synthesizing the parachloroo-nitroacetanilide by taking the diketene as the raw material, the obtained intermediate state is an active center of the reaction, but the strong activity of the intermediate state also can cause side reaction, the parachloroo-nitroacetanilide is synthesized by using the diketene at present to obtain the product with 88-92 percent of content and 70-80 percent of yield, and the main reason is that the parachloroo-nitroacetanilide continuously reacts with the intermediate state to generate impurities because of high intermediate state activity except that the residual of the parachloroo-nitroacetanilide is large; the method comprises the following steps:
besides, diketene has strong irritation, belongs to medium toxic substances, has strong irritation effect on eyes and respiratory tract due to steam, causes pulmonary edema due to serious people, can cause dermatitis or ulcer due to contact with skin, can cause cornea burn due to contact with eyes, and can cause liver cirrhosis due to contact with higher concentration for a long time. And the reaction system is subjected to violent polymerization in the presence of inorganic acid, alkali and amine catalysts, and the discharged gas explodes the container, so that certain potential safety hazards exist, and the yield is difficult to stabilize.
Therefore, raw materials with low toxicity and high safety are adopted to replace diketene to prepare the p-chloro-o-nitroacetoacetanilide, and the method has great significance in improving the yield and the product content of the reaction.
Disclosure of Invention
Aiming at a plurality of problems existing in the technology, the invention provides a high-safety synthesis method of the para-chloro-o-nitroacetoacetanilide, which utilizes methyl acetoacetate, ethyl acetoacetate or tert-butyl acetoacetate to replace the diketene in the prior art and redefines the dosage and reaction conditions of reactants, thereby overcoming a plurality of defects of adopting the diketene as raw materials, obtaining the para-chloro-o-nitroacetoacetanilide product with the highest content of more than 98 percent, having the yield of more than 96 percent, being applicable after three-stage condensation of waste gas, being used as a solvent, recovering low-content para-chloro-o-nitroacetoacetanilide by concentrating and secondary crystallization of crystallization filtrate, further reducing solid waste and lowering production cost.
In order to solve the related problems in the prior art, the inventor replaces the diketene in the prior art with methyl acetoacetate, ethyl acetoacetate or tert-butyl acetoacetate, and the corresponding reaction equation is as follows:
compared with the prior art, the reaction is milder than the reaction using diketene, but the byproduct alcohol is continuously separated out through the rectifying tower due to the generation of the byproduct, so that the forward direction of the reaction is ensured, otherwise, the reaction speed is low, the whole reaction is not carried out to a certain extent, and the yield of the whole reaction is influenced, therefore, the inventor adopts the following specific technical scheme:
a high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to a mass ratio of 1:4, enhancing heat until reflux, dropwise adding methyl acetoacetate or ethyl acetoacetate or tert-butyl acetoacetate with a molar equivalent of 1.05-1.15 times of that of the p-chloro-o-nitroaniline into a reaction system, keeping the reflux temperature for reaction for 3-4 hours, condensing toluene through a rectifying column, returning reaction byproducts methanol, ethanol or tert-butanol to a reaction bottle, condensing the reaction byproducts methanol, ethanol or tert-butanol through the rectifying column and a secondary condensing device, and returning the reaction byproducts methanol, ethanol or tert-butanol to a shunting device, wherein a cock of the shunting device is opened at the beginning of the reaction, and timely extracting the byproducts to ensure that the reaction is carried out forward;
cooling to 0-5 ℃ after the reaction is finished, carrying out suction filtration, and drying and detecting a filter cake; recovering toluene from the crystallization filtrate by reduced pressure distillation, cooling mother liquor, crystallizing again, filtering at 0-5 ℃, and drying and detecting a filter cake; combining and calculating the yield;
the waste gas generated in the reaction process is mainly toluene and contains a small amount of byproduct alcohol, the waste gas is subjected to condensation recovery and then is washed once by 0.4 times of volume of water at 20-30 ℃, the organic phase is subjected to normal pressure water after liquid separation, the alcohol content and the water content in the organic phase are detected, the alcohol content is less than or equal to 0.5%, the water content is less than or equal to 0.1%, and the waste gas is qualified and can be used for the next batch of reaction.
In the process, the reflux is realized in a heating mode to promote the distillation column to collect fractions, for example, the voltage of a heating sleeve is increased, and the temperature is set to be high by heating with an oil bath;
further, the reaction time is 4 hours; the dripping substance is ethyl acetoacetate, so that the cost can be reduced better, and the yield can be improved.
Through detection, the reaction conversion rate can reach 99%, the content of the p-chloro-o-nitroacetoacetanilide obtained by cooling and crystallizing a reaction system reaches more than 98%, and the yield reaches more than 92%; the crystallization filtrate is concentrated, cooled and crystallized to obtain a secondary crystallization product, wherein the content of the p-chloro-o-nitroacetoacetanilide reaches more than 85 percent, the reduced yield reaches more than 4 percent, and the total yield reaches more than 96 percent, which are obviously superior to the prior art.
In summary, by adopting the process, a plurality of defects of adopting diketene as a raw material are overcome, the p-chloro-o-nitroacetoacetanilide product with the highest content of more than 98 percent can be obtained, the yield can reach more than 96 percent, waste gas can be reused after three-stage condensation treatment, a solvent can be reused, and crystallization filtrate is concentrated and secondarily crystallized to recover low-content p-chloro-o-nitroacetoacetanilide, so that solid waste is further reduced, and the production cost is reduced.
Drawings
FIG. 1 is a schematic illustration of a reaction apparatus of the present application in a laboratory;
in the figure, toluene is condensed by a rectifying column and then returned to a reaction bottle, and reaction byproducts, namely methanol, ethanol or tertiary butanol, are condensed by the rectifying column and a secondary condensing device and then returned to a flow dividing device, wherein a cock of the flow dividing device is opened in the initial reaction, and the byproducts are timely extracted to ensure that the reaction is carried out in the forward direction; exhaust gas is discharged from the upper part of the secondary condensing device, and when the exhaust gas is collected for treatment, the secondary condensing device is provided with a diversion device and a tertiary condensing device, at the moment, the secondary condensing uses circulating water for condensation, and the tertiary condensing uses cold brine for condensation.
Detailed Description
The above-described aspects of the present invention will be described in further detail by way of the following embodiments, but it should not be construed that the scope of the above-described subject matter of the present invention is limited to the following examples. All techniques realized based on the above description of the present invention are within the scope of the present invention, and the following examples are accomplished by conventional techniques unless otherwise specified.
Example 1
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.05 times mole equivalent of methyl acetoacetate into a reaction system, keeping the reflux temperature for 2h for reaction, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct methanol by the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97%, the yield is 90%, recovering toluene from crystallization filtrate through reduced pressure distillation, cooling mother liquor, carrying out secondary crystallization, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 85%, the yield is 4%, and the total yield is 94%.
Example 2
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.10 times molar equivalent of methyl acetoacetate into a reaction system, keeping the reflux temperature for 2h for reaction, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct methanol by the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.2%, the yield is 90.6%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 85.7%, the yield is 4.2%, and the total yield is 94.8%.
Example 3
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.15 times molar equivalent of methyl acetoacetate into a reaction system, keeping the reflux temperature for 2h for reaction, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct methanol by the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.3%, the yield is 90.6%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 86%, the yield is 4.4%, and the total yield is 95%.
Example 4
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.05 times mole equivalent of methyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 3 hours, condensing toluene through a rectifying column, returning the condensed toluene to a reaction bottle, condensing reaction byproduct methanol through the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.2%, the yield is 90.8%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 87%, the yield is 4.2%, and the total yield is 95%.
Example 5
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.10 times molar equivalent of methyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 3 hours, condensing toluene through a rectifying column, returning the condensed toluene to a reaction bottle, condensing reaction byproduct methanol through the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.5%, the yield is 91%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 86.8%, the yield is 4.8%, and the total yield is 95.8%.
Example 6
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.15 times molar equivalent of methyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 3 hours, condensing toluene through a rectifying column, returning the condensed toluene to a reaction bottle, condensing reaction byproduct methanol through the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.5%, the yield is 91%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 87.2%, the yield is 5%, and the total yield is 96%.
Example 7
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.05 times mole equivalent of methyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 4 hours, condensing toluene through a rectifying column, returning the condensed toluene to a reaction bottle, condensing reaction byproduct methanol through the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.5%, the yield is 90.9%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 87%, the yield is 5%, and the total yield is 95.9%.
Example 8
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.10 times molar equivalent of methyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 4 hours, condensing toluene through a rectifying column, returning the condensed toluene to a reaction bottle, condensing reaction byproduct methanol through the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.4%, the yield is 91%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 86.4%, the yield is 5.4%, and the total yield is 96.4%.
Example 9
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.15 times molar equivalent of methyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 4 hours, condensing toluene through a rectifying column, returning the condensed toluene to a reaction bottle, condensing reaction byproduct methanol through the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.4%, the yield is 91.2%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 86.6%, the yield is 5.4%, and the total yield is 96.6%.
Example 10
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.05 times mol equivalent of ethyl acetoacetate into a reaction system, keeping the reflux temperature for 2h for reaction, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing ethanol which is a reaction byproduct by the rectifying column and a secondary condensing device, returning the condensed toluene to a splitting device, opening a cock of the splitting device at the beginning of reaction, timely extracting the byproduct to ensure that the reaction is carried out in the forward direction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.4%, the yield is 87.6%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 87%, the yield is 3.8%, and the total yield is 91.4%.
Example 11
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.10 times molar equivalent of ethyl acetoacetate into a reaction system, keeping the reflux temperature for 2h for reaction, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing ethanol which is a reaction byproduct by the rectifying column and a secondary condensing device, returning the condensed toluene to a splitting device, opening a cock of the splitting device at the beginning of reaction, timely extracting the byproduct to ensure that the reaction is carried out in the forward direction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.6%, the yield is 88.2%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 87.4%, the yield is 4.1%, and the total yield is 92.3%.
Example 12
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.15 times molar equivalent of ethyl acetoacetate into a reaction system, keeping the reflux temperature for 2h for reaction, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing ethanol which is a reaction byproduct by the rectifying column and a secondary condensing device, returning the condensed toluene to a splitting device, opening a cock of the splitting device at the beginning of reaction, timely extracting the byproduct to ensure that the reaction is carried out in the forward direction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.6%, the yield is 89%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 87.4%, the yield is 4.1%, and the total yield is 93.1%.
Example 13
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.05 times mol equivalent of ethyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 3 hours, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing ethanol which is a reaction byproduct by the rectifying column and a secondary condensing device, returning the condensed toluene to a splitting device, opening a cock of the splitting device at the beginning of reaction, timely extracting the byproduct to ensure that the reaction is carried out in the forward direction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.8%, the yield is 89.7%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 88%, the yield is 4.6%, and the total yield is 94.3%.
Example 14
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.10 times molar equivalent of ethyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 3 hours, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing ethanol which is a reaction byproduct by the rectifying column and a secondary condensing device, returning the condensed toluene to a splitting device, opening a cock of the splitting device at the beginning of reaction, timely extracting the byproduct to ensure that the reaction is carried out in the forward direction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.4%, the yield is 89.4%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 87.5%, the yield is 4.8%, and the total yield is 94.2%.
Example 15
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.15 times molar equivalent of ethyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 3 hours, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing ethanol which is a reaction byproduct by the rectifying column and a secondary condensing device, returning the condensed toluene to a splitting device, opening a cock of the splitting device at the beginning of reaction, timely extracting the byproduct to ensure that the reaction is carried out in the forward direction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.8%, the yield is 89.7%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 88%, the yield is 5.1%, and the total yield is 94.8%.
Example 16
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.05 times mol equivalent of ethyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 4 hours, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing ethanol which is a reaction byproduct by the rectifying column and a secondary condensing device, returning the condensed toluene to a splitting device, opening a cock of the splitting device at the beginning of reaction, timely extracting the byproduct to ensure that the reaction is carried out in the forward direction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98%, the yield is 90.8%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 87.5%, the yield is 5.6%, and the total yield is 96.4%.
Example 17
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.10 times molar equivalent of ethyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 4 hours, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing ethanol which is a reaction byproduct by the rectifying column and a secondary condensing device, returning the condensed toluene to a splitting device, opening a cock of the splitting device at the beginning of reaction, timely extracting the byproduct to ensure that the reaction is carried out in the forward direction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98%, the yield is 91%, recovering toluene from crystallization filtrate through reduced pressure distillation, cooling mother liquor, carrying out secondary crystallization, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 87.6%, the yield is 5.4%, and the total yield is 96.4%.
Example 18
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.15 times molar equivalent of ethyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 4 hours, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing ethanol which is a reaction byproduct by the rectifying column and a secondary condensing device, returning the condensed toluene to a splitting device, opening a cock of the splitting device at the beginning of reaction, timely extracting the byproduct to ensure that the reaction is carried out in the forward direction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98.1%, the yield is 91%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 88%, the yield is 5.1%, and the total yield is 96.1%.
Example 19
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.05 times mol equivalent of tert-butyl acetoacetate into a reaction system, keeping the reflux temperature for 2h for reaction, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct tert-butanol by the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98.4%, the yield is 92.1%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 90%, the yield is 4.1%, and the total yield is 96.2%.
Example 20
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.10 times mol equivalent of tert-butyl acetoacetate into a reaction system, keeping the reflux temperature for 2h for reaction, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct tert-butanol by the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98.5%, the yield is 92.5%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 90.1%, the yield is 4.3%, and the total yield is 96.7%.
Example 21
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.15 times of molar equivalent of tert-butyl acetoacetate into a reaction system, keeping the reflux temperature for 2h for reaction, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct tert-butanol by the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98.7%, the yield is 92.5%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 89.1%, the yield is 4.1%, and the total yield is 96.6%.
Example 22
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.05 times mol equivalent of tert-butyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 3h, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct tert-butanol by the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98.5%, the yield is 92.6%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 89.6%, the yield is 4.7%, and the total yield is 97.3%.
Example 23
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.10 times mol equivalent of tert-butyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 3h, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct tert-butanol by the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98.4%, the yield is 92.8%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 89.1%, the yield is 4.9%, and the total yield is 97.7%.
Example 24
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.15 times of molar equivalent of tert-butyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 3h, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct tert-butanol by the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98.6%, the yield is 92.4%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 90%, the yield is 4.1%, and the total yield is 96.5%.
Example 25
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.05 times mol equivalent of tert-butyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 4 hours, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct tert-butanol by the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of the reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98.3%, the yield is 92.1%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 89.6%, the yield is 3.9%, and the total yield is 96.0%.
Example 26
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.10 times mol equivalent of tert-butyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 4 hours, condensing toluene by a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct tert-butanol by the rectifying column and a secondary condensing device, returning the condensed toluene to a flow dividing device, opening a cock of the flow dividing device at the beginning of the reaction, timely extracting the byproduct to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98.4%, the yield is 92.6%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 89.9%, the yield is 4.6%, and the total yield is 97.2%.
Example 27
A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to the mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.15 times of molar equivalent of tert-butyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 4 hours, condensing toluene through a rectifying column, returning the condensed toluene to a reaction bottle, condensing a reaction byproduct tert-butanol through the rectifying column and a secondary condensing device, returning the condensed tert-butanol to a flow dividing device,
the tap of the flow dividing device is opened at the beginning of the reaction, byproducts are timely extracted to ensure the forward reaction, after the reaction is finished, the temperature is reduced to about 5 ℃, the filtration is carried out, the filter cake is dried and detected, the content is 98.5%, the yield is 92.4%, the crystallization filtrate is distilled under reduced pressure to recover toluene, the mother liquor is cooled and crystallized for the second time, the filtration is carried out at about 5 ℃, the filter cake is dried and detected, the content is 89.4%, the yield is 4.4%, and the total yield is 96.8%.
Example 28
30g of the waste gas condensate in the examples 10-18 (toluene and containing a small amount of byproduct alcohol) is washed once by 12g of water, the organic phase is recycled for 30min after liquid separation, the ethanol content is detected to be 0.3 percent, the water content is detected to be 0.08 percent, the organic phase is mixed with fresh toluene, p-chloro-o-nitroaniline and the mixed toluene are prepared into a solution according to the mass ratio of 1:4, the solution is heated to reflux, 1.15 times molar equivalent of ethyl acetoacetate is dropwise added into a reaction system, the reflux temperature is kept for 4h, toluene is returned to a reaction bottle after being condensed by a rectifying column, the reaction byproduct ethanol is returned to a splitting device after being condensed by the rectifying column and a secondary condensing device, the splitting device is opened in the beginning of the reaction, the by-product cock is timely picked up to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 97.9%, the yield is 91%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 87%, the yield is 5.3%, and the total yield is 96.3%.
Example 29
The toluene recovered from the last crystallization filtrate in example 18 by reduced pressure distillation is detected, the detection result shows that the ethanol content is 2.3 percent, the organic phase is water-added, the ethanol content is 0.27 percent, the water content is 0.06 percent, the organic phase is mixed with fresh toluene, p-chloro-o-nitroaniline and the mixed toluene are prepared into solution according to the mass ratio of 1:4, the heat is enhanced to reflux, 1.15 times molar equivalent of ethyl acetoacetate is dropwise added into a reaction system, the reflux temperature is kept for 4 hours, the toluene is condensed by a rectifying column and then returns to a reaction bottle, the ethanol as a reaction byproduct is condensed by the rectifying column and a secondary condensing device and then returns to a shunting device, a cock of the shunting device is opened at the beginning of the reaction, the byproduct is timely extracted to ensure the forward reaction,
cooling to about 5 ℃ after the reaction is finished, carrying out suction filtration, drying and detecting a filter cake, wherein the content is 98.1%, the yield is 91.1%, cooling mother liquor for secondary crystallization after toluene is recovered from crystallization filtrate through reduced pressure distillation, carrying out suction filtration at about 5 ℃, drying and detecting a filter cake, the content is 87%, the yield is 4.8%, and the total yield is 95.9%.
Claims (2)
1. A high-safety synthesis method of p-chloro-o-nitroacetoacetanilide is characterized by comprising the following steps: the method comprises the following specific steps:
preparing p-chloro-o-nitroaniline and toluene into a solution according to a mass ratio of 1:4, enhancing heat until reflux, dropwise adding 1.05-1.15 times of molar equivalent of tert-butyl acetoacetate into a reaction system, keeping the reflux temperature for reaction for 3-4 hours, condensing toluene through a rectifying column, returning the reaction byproduct tert-butanol to a reaction bottle, condensing the reaction byproduct tert-butanol through the rectifying column and a secondary condensing device, returning the reaction byproduct tert-butanol to a flow dividing device, and opening a cock of the flow dividing device in the initial reaction, and timely extracting the byproduct to ensure that the reaction is carried out in the forward direction;
cooling to 0-5 ℃ after the reaction is finished, carrying out suction filtration, and drying and detecting a filter cake; recovering toluene from the crystallization filtrate by reduced pressure distillation, cooling mother liquor, crystallizing again, filtering at 0-5 ℃, and drying and detecting a filter cake; the yields were calculated in combination.
2. The method for synthesizing parachloronitroacetanilide with high safety according to claim 1, wherein the reaction time is 4 hours.
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