CN116589394A - Process for producing chlorfenapyr by taking proline as acid binding agent - Google Patents
Process for producing chlorfenapyr by taking proline as acid binding agent Download PDFInfo
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- CN116589394A CN116589394A CN202310570354.9A CN202310570354A CN116589394A CN 116589394 A CN116589394 A CN 116589394A CN 202310570354 A CN202310570354 A CN 202310570354A CN 116589394 A CN116589394 A CN 116589394A
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- proline
- chlorfenapyr
- binding agent
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- toluene
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- ONIBWKKTOPOVIA-UHFFFAOYSA-N Proline Natural products OC(=O)C1CCCN1 ONIBWKKTOPOVIA-UHFFFAOYSA-N 0.000 title claims abstract description 103
- CWFOCCVIPCEQCK-UHFFFAOYSA-N chlorfenapyr Chemical compound BrC1=C(C(F)(F)F)N(COCC)C(C=2C=CC(Cl)=CC=2)=C1C#N CWFOCCVIPCEQCK-UHFFFAOYSA-N 0.000 title claims abstract description 87
- 238000000034 method Methods 0.000 title claims abstract description 57
- 239000002253 acid Substances 0.000 title claims abstract description 52
- 239000011230 binding agent Substances 0.000 title claims abstract description 51
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 117
- 239000012074 organic phase Substances 0.000 claims abstract description 67
- 239000012071 phase Substances 0.000 claims abstract description 65
- 238000003756 stirring Methods 0.000 claims abstract description 55
- 238000011084 recovery Methods 0.000 claims abstract description 34
- 239000011259 mixed solution Substances 0.000 claims abstract description 22
- XNFIRYXKTXAHAC-UHFFFAOYSA-N tralopyril Chemical compound BrC1=C(C(F)(F)F)NC(C=2C=CC(Cl)=CC=2)=C1C#N XNFIRYXKTXAHAC-UHFFFAOYSA-N 0.000 claims abstract description 20
- 238000010992 reflux Methods 0.000 claims abstract description 17
- KLKFAASOGCDTDT-UHFFFAOYSA-N ethoxymethoxyethane Chemical compound CCOCOCC KLKFAASOGCDTDT-UHFFFAOYSA-N 0.000 claims abstract description 16
- 239000003960 organic solvent Substances 0.000 claims abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 114
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 84
- 239000000243 solution Substances 0.000 claims description 54
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 28
- 238000001816 cooling Methods 0.000 claims description 26
- NJSUFZNXBBXAAC-UHFFFAOYSA-N ethanol;toluene Chemical compound CCO.CC1=CC=CC=C1 NJSUFZNXBBXAAC-UHFFFAOYSA-N 0.000 claims description 26
- 239000012046 mixed solvent Substances 0.000 claims description 26
- 238000001035 drying Methods 0.000 claims description 25
- 238000002156 mixing Methods 0.000 claims description 24
- 238000004821 distillation Methods 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 239000007858 starting material Substances 0.000 claims 1
- 238000007599 discharging Methods 0.000 abstract description 13
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract 1
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 98
- 238000006243 chemical reaction Methods 0.000 description 91
- ONIBWKKTOPOVIA-BYPYZUCNSA-N L-Proline Chemical compound OC(=O)[C@@H]1CCCN1 ONIBWKKTOPOVIA-BYPYZUCNSA-N 0.000 description 85
- 230000000052 comparative effect Effects 0.000 description 23
- 150000003147 proline derivatives Chemical class 0.000 description 23
- 238000010438 heat treatment Methods 0.000 description 11
- 239000002904 solvent Substances 0.000 description 11
- 239000000758 substrate Substances 0.000 description 11
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 239000007789 gas Substances 0.000 description 6
- 229910021529 ammonia Inorganic materials 0.000 description 4
- XKMRRTOUMJRJIA-UHFFFAOYSA-N ammonia nh3 Chemical compound N.N XKMRRTOUMJRJIA-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 239000010865 sewage Substances 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- 230000000895 acaricidal effect Effects 0.000 description 2
- 230000000749 insecticidal effect Effects 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 1
- DHVLDKHFGIVEIP-UHFFFAOYSA-N 2-bromo-2-(bromomethyl)pentanedinitrile Chemical compound BrCC(Br)(C#N)CCC#N DHVLDKHFGIVEIP-UHFFFAOYSA-N 0.000 description 1
- 241000238876 Acari Species 0.000 description 1
- 244000003416 Asparagus officinalis Species 0.000 description 1
- 235000005340 Asparagus officinalis Nutrition 0.000 description 1
- 241000500437 Plutella xylostella Species 0.000 description 1
- 241000607479 Yersinia pestis Species 0.000 description 1
- 239000000642 acaricide Substances 0.000 description 1
- 230000006978 adaptation Effects 0.000 description 1
- 239000003242 anti bacterial agent Substances 0.000 description 1
- 229940088710 antibiotic agent Drugs 0.000 description 1
- -1 aryl group pyrrole compound Chemical class 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 230000001055 chewing effect Effects 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 239000013505 freshwater Substances 0.000 description 1
- 125000001841 imino group Chemical group [H]N=* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002147 killing effect Effects 0.000 description 1
- 238000002844 melting Methods 0.000 description 1
- 230000008018 melting Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000002244 precipitate Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 238000012827 research and development Methods 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 210000002784 stomach Anatomy 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 230000009885 systemic effect Effects 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 239000002912 waste gas Substances 0.000 description 1
- 239000002699 waste material Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/30—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D207/34—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02A—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE
- Y02A50/00—TECHNOLOGIES FOR ADAPTATION TO CLIMATE CHANGE in human health protection, e.g. against extreme weather
- Y02A50/30—Against vector-borne diseases, e.g. mosquito-borne, fly-borne, tick-borne or waterborne diseases whose impact is exacerbated by climate change
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pyrrole Compounds (AREA)
Abstract
The invention provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which comprises the steps of taking 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile and diethoxymethane as initial raw materials under the condition of an organic solvent, stirring for at least 0.5 hour at the temperature of 48-52 ℃ to prepare a mixed solution, then taking proline as the acid binding agent, refluxing for 2 hours at the temperature of 50-60 ℃, adding clear water, stirring, standing for 2 hours, discharging a water phase, and carrying out post treatment on the rest organic phase to obtain the chlorfenapyr. The invention reduces the comprehensive cost of the chlorfenapyr synthesis process and the acid-binding agent recovery process, and improves the recovery rate of the acid-binding agent.
Description
Technical Field
The invention relates to the technical field of production of chlorfenapyr, in particular to a process for producing chlorfenapyr by taking proline as an acid binding agent.
Background
The chlorfenapyr is an arylpyrrole insecticidal acaricide, and the English common name is: chlorfenapyr, chemical name: 4-bromo-2- (p-chlorophenyl) -1-ethoxymethyl-5- (trifluoromethyl) pyrrole-3-carbonitrile. The chemical structural formula is as follows:
the basic physicochemical data are as follows:
CAS accession number: 122453-73-0; the molecular formula: c (C) 15 H 11 BrCIF 3 N 2 O; relative molecular mass: 407.62; melting point: 91-92 ℃.
The chlorfenapyr is an aryl group pyrrole compound synthesized by modifying natural antibiotics, has high efficiency and broad spectrum, and has stomach toxicity, certain contact killing effect and systemic activity. Has moderate effect on crops, has excellent control effect on boring, piercing and sucking and chewing pests and mites, has special effects on resistant plutella xylostella, asparagus caterpillar and the like, and is a high-efficiency insecticidal and acaricidal agent worthy of research and development.
In the synthetic production of the chlorfenapyr, triethylamine is widely used as an acid binding agent in domestic technology, and the triethylamine is cheap and easy to obtain and is popular. However, the boiling point of triethylamine is only 89 degrees, the triethylamine is easy to volatilize, ammonia taste is heavy, the solubility of the triethylamine in water is 170 g/L20 ℃, distillation operation is carried out in a triethylamine recovery process, a large amount of triethylamine enters tail gas emission, ammonia nitrogen value in water is high, the cost of tail gas treatment and sewage treatment is high, and the recovery rate of the acid-binding agent triethylamine is low.
Disclosure of Invention
In view of the above, the invention provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which reduces the comprehensive cost of the chlorfenapyr synthesis process and the acid binding agent recovery process and improves the recovery rate of the acid binding agent.
In order to achieve the aim, the invention provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which adopts the following technical scheme:
a process for preparing bromothalonil by using proline as acid-binding agent includes such steps as preparing mixed solution from 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-carbonitrile and diethoxymethane by stirring at 48-52 deg.C for 0.5 hr, reflux for 2 hr at 50-60 deg.C by using proline as acid-binding agent, adding clean water, stirring, extracting proline salt, laying aside for 2 hr, discharging water phase, and post-treating.
Further, the molar ratio of the 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-carbonitrile, the diethoxymethane and the organic solvent was 1:2.5:9.
Further, preparing a mixed solution at 50 ℃; controlling the temperature to be 50 ℃, and adding proline into the mixed solution; the reflux temperature was maintained at 50-55 ℃.
Further, the molar ratio of the proline to the 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-carbonitrile was 2:1.
Further, the mass ratio of the clear water to the mixed solution is (0.6-0.7): 1.
Further, the specific operation steps of the post-treatment are as follows: controlling the temperature to be 50-60 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to 25-30 ℃; then mixing toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution; and then cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr.
Further, the temperature was kept at 50℃and the organic phase was distilled under reduced pressure until no fraction was obtained.
Further, after the concentrated organic phase was obtained, the temperature was lowered to 25 ℃.
Further, in the toluene-ethanol mixed solvent, the volume ratio of toluene to ethanol is 1:2.
Further, the method for recovering proline is as follows: and (3) dropwise adding sodium hydroxide solution into the discharged water phase, stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing at room temperature for 1 hour, and centrifugally drying to obtain the proline.
The technical scheme of the invention at least comprises the following beneficial effects:
1. compared with triethylamine which is an acid binding agent used in the prior art, the method has the advantages that proline is an imino acid which is a solid substance, is nontoxic and nonvolatile, and shows no ammonia-containing waste gas emission and no water residue after water treatment in the production process, and in actual production, the proline is proved to be a safe, environment-friendly and nontoxic acid binding agent;
2. in the prior art, triethylamine is used as an acid binding agent, the boiling point is only 89 ℃, the triethylamine is volatile, ammonia taste is heavy, distillation operation is carried out in the synthesis and triethylamine recovery processes, a large amount of triethylamine enters into tail gas emission, ammonia nitrogen value in water is high, sewage treatment and tail gas treatment costs are very high, the recovery rate of the triethylamine is low, and multi-year data show that three wastes generated by single-treatment of the triethylamine are approximately 1 ten thousand yuan in average per ton cost.
3. The invention controls the temperature of the preparation mixed solution at 48-52 ℃, the temperature of the proline adding process at 48-52 ℃ and the temperature of the reflux stage at 50-60 ℃, keeps the temperature stable, and is more beneficial to improving the yield of the chlorfenapyr product;
the intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-carbonitrile precipitates due to the excessively low temperature, so that the reaction is not facilitated, and the intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-carbonitrile is easily damaged due to the excessively high temperature, so that the yield of the final chlorfenapyr is influenced;
4. the invention limits the clean water amount used for extracting the proline salt, the mass ratio of the clean water to the mixed solution is (0.6-0.7): 1, ensures that the proline salt is fully extracted, is beneficial to improving the recovery rate of the proline, and simultaneously avoids wasting water resources due to excessive water consumption.
Detailed Description
In order to make the objects, technical solutions and advantages of the embodiments of the present invention more clear, the technical solutions of the embodiments of the present invention will be clearly and completely described below in conjunction with the embodiments of the present invention. It will be apparent that the described embodiments are some, but not all, embodiments of the invention. All other embodiments, which are obtained by a person skilled in the art based on the described embodiments of the invention, fall within the scope of protection of the invention.
Example 1
The embodiment provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which comprises the following steps:
s1, 10kg of a chlorfenapyr intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, 7.44kg of diethoxymethane and 26kg of toluene are put into a reaction kettle;
s2, heating the temperature in the reaction kettle to 50 ℃, and stirring for 0.5 hour to enable the substrate to be fully dissolved in toluene as a solvent to obtain a mixed solution;
s3, slowly adding 8.23kg of proline into the reaction kettle, wherein in the process, the temperature of circulating water is reduced, and the temperature in the reaction kettle is controlled to be preferably 50 ℃;
s4, controlling the temperature in the reaction kettle to be 50-55 ℃, and refluxing for 2 hours;
s5, adding 30kg of clear water into the reaction kettle, stirring for 0.5 hour, extracting proline salt, fully dissolving the proline salt in the clear water, standing for 2 hours, layering an organic phase and a water phase, discharging the water phase, and leaving the organic phase in the reaction kettle;
s6, controlling the temperature in the reaction kettle to be kept at 50 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to room temperature of 25 ℃;
s7, mixing toluene and ethanol according to a volume ratio of 1:2 to obtain a toluene-ethanol mixed solvent, mixing the toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution;
s8, cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr, wherein the total amount of the chlorfenapyr is 11.1kg.
The method for recovering the proline comprises the following steps: and (3) dropwise adding a sodium hydroxide solution into the water phase discharged from the step (S5), stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing for 1 hour at room temperature, centrifugally drying to obtain 7.8kg of proline, calculating that the recovery rate of the proline is 94.8%, and repeatedly using the proline after detecting the content of the proline to be 97.6%.
Example 2
The embodiment provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which comprises the following steps:
s1, 10kg of a chlorfenapyr intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, 7.44kg of diethoxymethane and 26kg of toluene are put into a reaction kettle;
s2, heating the temperature in the reaction kettle to 48 ℃, and stirring for 0.8 hour to enable the substrate to be fully dissolved in toluene as a solvent to obtain a mixed solution;
s3, slowly adding 8.23kg of proline into the reaction kettle, wherein in the process, the temperature of circulating water is reduced, and the temperature in the reaction kettle is controlled to be kept at 48 ℃;
s4, controlling the temperature in the reaction kettle to be 50-55 ℃, and refluxing for 2 hours;
s5, adding 30kg of clear water into the reaction kettle, stirring for 0.5 hour, extracting proline salt, fully dissolving the proline salt in the clear water, standing for 2 hours, layering an organic phase and a water phase, discharging the water phase, and leaving the organic phase in the reaction kettle;
s6, controlling the temperature in the reaction kettle to be kept at 50 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to room temperature of 25 ℃;
s7, mixing toluene and ethanol according to a volume ratio of 1:2 to obtain a toluene-ethanol mixed solvent, mixing the toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution;
s8, cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr, wherein the total amount of the chlorfenapyr is 11.08kg.
The method for recovering the proline comprises the following steps: and (3) dropwise adding a sodium hydroxide solution into the water phase discharged from the step (S5), stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing for 1 hour at room temperature, centrifugally drying to obtain 7.6kg of proline, calculating that the recovery rate of the proline is 92.3%, and repeatedly using the detected content of the proline as a result.
Example 3
The embodiment provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which comprises the following steps:
s1, 10kg of a chlorfenapyr intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, 7.44kg of diethoxymethane and 26kg of toluene are put into a reaction kettle;
s2, heating the temperature in the reaction kettle to 52 ℃, and stirring for 0.8 hour to enable the substrate to be fully dissolved in toluene as a solvent to obtain a mixed solution;
s3, slowly adding 8.23kg of proline into the reaction kettle, wherein in the process, the temperature of circulating water is reduced, and the temperature in the reaction kettle is controlled to be kept at 52 ℃;
s4, controlling the temperature in the reaction kettle to be 50-55 ℃, and refluxing for 2 hours;
s5, adding 30kg of clear water into the reaction kettle, stirring for 0.5 hour, extracting proline salt, fully dissolving the proline salt in the clear water, standing for 2 hours, layering an organic phase and a water phase, discharging the water phase, and leaving the organic phase in the reaction kettle;
s6, controlling the temperature in the reaction kettle to be kept at 50 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to room temperature of 25 ℃;
s7, mixing toluene and ethanol according to a volume ratio of 1:2 to obtain a toluene-ethanol mixed solvent, mixing the toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution;
s8, cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr, wherein the total amount of the chlorfenapyr is 11.09kg.
The method for recovering the proline comprises the following steps: and (3) dropwise adding a sodium hydroxide solution into the water phase discharged from the step (S5), stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing for 1 hour at room temperature, centrifugally drying to obtain 7.5kg of proline, and calculating that the recovery rate of the proline is 91.1%, and the detected content is 97.5%, so that the proline can be repeatedly used.
Example 4
The embodiment provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which comprises the following steps:
s1, 10kg of a chlorfenapyr intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, 7.44kg of diethoxymethane and 26kg of toluene are put into a reaction kettle;
s2, heating the temperature in the reaction kettle to 50 ℃, and stirring for 0.5 hour to enable the substrate to be fully dissolved in toluene as a solvent to obtain a mixed solution;
s3, slowly adding 8.23kg of proline into the reaction kettle, wherein in the process, the temperature of circulating water is reduced, and the temperature in the reaction kettle is controlled to be preferably 50 ℃;
s4, controlling the temperature in the reaction kettle to be 55-60 ℃ and refluxing for 2 hours;
s5, adding 30kg of clear water into the reaction kettle, stirring for 0.5 hour, extracting proline salt, fully dissolving the proline salt in the clear water, standing for 2 hours, layering an organic phase and a water phase, discharging the water phase, and leaving the organic phase in the reaction kettle;
s6, controlling the temperature in the reaction kettle to be kept at 50 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to room temperature of 25 ℃;
s7, mixing toluene and ethanol according to a volume ratio of 1:2 to obtain a toluene-ethanol mixed solvent, mixing the toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution;
s8, cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr, wherein the total amount of the chlorfenapyr is 11.09kg.
The method for recovering the proline comprises the following steps: and (3) dropwise adding a sodium hydroxide solution into the water phase discharged from the step (S5), stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing for 1 hour at room temperature, centrifugally drying to obtain 7.7kg of proline, and calculating that the recovery rate of the proline is 93.6%, wherein the detected content is 97.8%, and the proline can be repeatedly used.
Example 5
The embodiment provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which comprises the following steps:
s1, 10kg of a chlorfenapyr intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, 7.44kg of diethoxymethane and 26kg of toluene are put into a reaction kettle;
s2, heating the temperature in the reaction kettle to 50 ℃, and stirring for 0.5 hour to enable the substrate to be fully dissolved in toluene as a solvent to obtain a mixed solution;
s3, slowly adding 8.23kg of proline into the reaction kettle, wherein in the process, the temperature of circulating water is reduced, and the temperature in the reaction kettle is controlled to be preferably 50 ℃;
s4, controlling the temperature in the reaction kettle to be 50-55 ℃, and refluxing for 2 hours;
s5, adding 28kg of clear water into the reaction kettle, stirring for 0.8 hour, extracting proline salt, fully dissolving the proline salt in the clear water, standing for 2 hours, layering an organic phase and a water phase, discharging the water phase, and leaving the organic phase in the reaction kettle;
s6, controlling the temperature in the reaction kettle to be kept at 50 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to room temperature of 25 ℃;
s7, mixing toluene and ethanol according to a volume ratio of 1:2 to obtain a toluene-ethanol mixed solvent, mixing the toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution;
s8, cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr, wherein the total amount of the chlorfenapyr is 11.11kg.
The method for recovering the proline comprises the following steps: and (3) dropwise adding a sodium hydroxide solution into the water phase discharged from the step (S5), stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing for 1 hour at room temperature, centrifugally drying to obtain 7.8kg of proline, calculating that the recovery rate of the proline is 94.8%, and repeatedly using the proline after detecting the content of the proline to be 97.5%.
Example 6
The embodiment provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which comprises the following steps:
s1, 10kg of a chlorfenapyr intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, 7.44kg of diethoxymethane and 26kg of toluene are put into a reaction kettle;
s2, heating the temperature in the reaction kettle to 50 ℃, and stirring for 0.5 hour to enable the substrate to be fully dissolved in toluene as a solvent to obtain a mixed solution;
s3, slowly adding 8.23kg of proline into the reaction kettle, wherein in the process, the temperature of circulating water is reduced, and the temperature in the reaction kettle is controlled to be preferably 50 ℃;
s4, controlling the temperature in the reaction kettle to be 50-55 ℃, and refluxing for 2 hours;
s5, adding 30kg of clear water into the reaction kettle, stirring for 0.5 hour, extracting proline salt, fully dissolving the proline salt in the clear water, standing for 2 hours, layering an organic phase and a water phase, discharging the water phase, and leaving the organic phase in the reaction kettle;
s6, controlling the temperature in the reaction kettle to be kept at 55 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to room temperature of 25 ℃;
s7, mixing toluene and ethanol according to a volume ratio of 1:2 to obtain a toluene-ethanol mixed solvent, mixing the toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution;
s8, cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr, wherein the total amount of the chlorfenapyr is 11.07kg.
The method for recovering the proline comprises the following steps: and (3) dropwise adding a sodium hydroxide solution into the water phase discharged from the step (S5), stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing for 1 hour at room temperature, centrifugally drying to obtain 7.8kg of proline, calculating that the recovery rate of the proline is 94.8%, and repeatedly using the proline after detecting the content of the proline to be 97.9%.
Example 7
The embodiment provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which comprises the following steps:
s1, 10kg of a chlorfenapyr intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, 7.44kg of diethoxymethane and 26kg of toluene are put into a reaction kettle;
s2, heating the temperature in the reaction kettle to 50 ℃, and stirring for 0.5 hour to enable the substrate to be fully dissolved in toluene as a solvent to obtain a mixed solution;
s3, slowly adding 8.23kg of proline into the reaction kettle, wherein in the process, the temperature of circulating water is reduced, and the temperature in the reaction kettle is controlled to be preferably 50 ℃;
s4, controlling the temperature in the reaction kettle to be 50-55 ℃, and refluxing for 2 hours;
s5, adding 30kg of clear water into the reaction kettle, stirring for 0.5 hour, extracting proline salt, fully dissolving the proline salt in the clear water, standing for 2 hours, layering an organic phase and a water phase, discharging the water phase, and leaving the organic phase in the reaction kettle;
s6, controlling the temperature in the reaction kettle to be kept at 60 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to room temperature of 25 ℃;
s7, mixing toluene and ethanol according to a volume ratio of 1:2 to obtain a toluene-ethanol mixed solvent, mixing the toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution;
s8, cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr, wherein the total amount of the chlorfenapyr is 11.07kg.
The method for recovering the proline comprises the following steps: and (3) dropwise adding a sodium hydroxide solution into the water phase discharged from the step (S5), stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing for 1 hour at room temperature, centrifugally drying to obtain 7.8kg of proline, calculating that the recovery rate of the proline is 94.8%, and repeatedly using the proline after detecting the content of the proline to be 97.6%.
Comparative example 1
The comparative example provides a process for producing chlorfenapyr by using triethylamine as an acid binding agent, which comprises the following steps:
s1, 10kg of a chlorfenapyr intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, 7.44kg of diethoxymethane and 26kg of toluene are put into a reaction kettle;
s2, heating the temperature in the reaction kettle to 50 ℃, and stirring for 0.5 hour to enable the substrate to be fully dissolved in toluene as a solvent to obtain a mixed solution;
s3, slowly dripping 7.22kg of triethylamine into the reaction kettle, wherein in the process, the temperature of circulating water is reduced, and the temperature in the reaction kettle is controlled to be preferably 50 ℃;
s4, controlling the temperature in the reaction kettle to be 50-55 ℃, and refluxing for 2 hours;
s5, adding 30kg of clear water into the reaction kettle, stirring for 0.5 hour, extracting triethylamine salt, fully transferring and dissolving the triethylamine salt in the water, standing for 2 hours, layering an organic phase and a water phase, discharging the water phase, and leaving the organic phase in the reaction kettle;
s6, controlling the temperature in the reaction kettle to be kept at 50 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to room temperature of 25 ℃;
s7, mixing toluene and ethanol according to a volume ratio of 1:2 to obtain a toluene-ethanol mixed solvent, mixing the toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution;
s8, cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr, wherein the total amount of the chlorfenapyr is 11.05kg.
The method for recovering triethylamine comprises the following steps: and S5, distilling the water phase discharged by about 50 ℃ under reduced pressure until no obvious distillate is distilled, wherein the distillate mainly comprises water, toluene, ethanol and other organic volatile impurities, then dropwise adding sodium hydroxide solution into the water phase, stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 7-8, standing at room temperature for 1 hour, distilling at normal pressure until the triethylamine and the water are separated, stirring at the same time until no distillate is obtained, distilling the distillate, namely crude triethylamine, circulating the crude triethylamine through a sodium hydroxide bed, absorbing the water by using sodium hydroxide, continuously and circularly washing for 1 hour, obtaining 5.05 kg of triethylamine, and repeatedly applying the triethylamine with the recovery rate of 69.9 percent and the detected triethylamine content of about 95 percent.
This comparative example differs from example 1 only in that: the acid-binding agent in this comparative example was triethylamine, and the acid-binding agent in example 1 was proline.
Comparison results: the yield of chlorfenapyr in this comparative example was 11.05kg, and the yield of chlorfenapyr in example 1 was 11.1kg, which revealed that the yield of chlorfenapyr in this comparative example was slightly lower than that in example 1;
the recovery rate of the acid-binding agent triethylamine in this comparative example was 5.05 kg, the recovery rate was 69.9%, the recovery rate of the acid-binding agent proline in example 1 was 7.8kg, and the recovery rate was 94.8%, which means that the recovery rate of the acid-binding agent triethylamine in this comparative example was significantly lower than the recovery rate of the acid-binding agent proline in example 1. The method is mainly characterized in that the boiling point of triethylamine is only 89 degrees, the triethylamine is easy to volatilize, ammonia taste is heavy, distillation operation is carried out in both the process of organically synthesizing the chlorfenapyr and the process of recovering the acid binding agent, a large amount of triethylamine enters into tail gas emission, the triethylamine is wasted, and the recovery rate of the triethylamine is low. Meanwhile, the ammonia nitrogen value in water is high, and the cost of tail gas treatment and sewage treatment is high.
Comparative example 2
The comparative example provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which comprises the following steps:
s1, 10kg of a chlorfenapyr intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, 7.44kg of diethoxymethane and 26kg of toluene are put into a reaction kettle;
s2, heating the temperature in the reaction kettle to 62 ℃, and stirring for 0.5 hour to enable the substrate to be fully dissolved in toluene as a solvent to obtain a mixed solution;
s3, slowly adding 8.23kg of proline into the reaction kettle, wherein in the process, the temperature of circulating water is reduced, and the temperature in the reaction kettle is controlled to be kept at 62 ℃;
s4, controlling the temperature in the reaction kettle to be kept at 62-66 ℃ and refluxing for 2 hours;
s5, adding 30kg of clear water into the reaction kettle, stirring for 0.5 hour, extracting proline salt, fully dissolving the proline salt in the clear water, standing for 2 hours, layering an organic phase and a water phase, discharging the water phase, and leaving the organic phase in the reaction kettle;
s6, controlling the temperature in the reaction kettle to be kept at 50 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to room temperature of 25 ℃;
s7, mixing toluene and ethanol according to a volume ratio of 1:2 to obtain a toluene-ethanol mixed solvent, mixing the toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution;
s8, cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr, wherein the total amount of the chlorfenapyr is 10.5kg.
The method for recovering the proline comprises the following steps: and (3) dropwise adding a sodium hydroxide solution into the water phase discharged from the step (S5), stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing for 1 hour at room temperature, centrifugally drying to obtain 7.8kg of proline, calculating that the recovery rate of the proline is 94.8%, and repeatedly using the proline after detecting the content of the proline to be 97.5%.
This comparative example differs from example 1 only in that: the control temperatures during S2, S3 and S4 are all outside the protection (limit) range of the present invention.
Comparison results: the yield of chlorfenapyr in this comparative example was 10.5kg, and the yield of chlorfenapyr in example 1 was 11.1kg, whereby it was found that the yield of chlorfenapyr in this comparative example was significantly lower than that in example 1. Indicating that too high a reaction temperature would decrease the yield of chlorfenapyr.
Comparative example 3
The comparative example provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which comprises the following steps:
s1, 10kg of a chlorfenapyr intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, 7.44kg of diethoxymethane and 26kg of toluene are put into a reaction kettle;
s2, heating the temperature in the reaction kettle to 45 ℃, and stirring for 0.5 hour to enable the substrate to be fully dissolved in toluene as a solvent to obtain a mixed solution;
s3, slowly adding 8.23kg of proline into the reaction kettle, wherein in the process, the temperature of circulating water is reduced, and the temperature in the reaction kettle is controlled to be kept at 45 ℃;
s4, controlling the temperature in the reaction kettle to be 42-46 ℃, and refluxing for 2 hours;
s5, adding 30kg of clear water into the reaction kettle, stirring for 0.5 hour, extracting proline salt, fully dissolving the proline salt in the clear water, standing for 2 hours, layering an organic phase and a water phase, discharging the water phase, and leaving the organic phase in the reaction kettle;
s6, controlling the temperature in the reaction kettle to be kept at 50 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to room temperature of 25 ℃;
s7, mixing toluene and ethanol according to a volume ratio of 1:2 to obtain a toluene-ethanol mixed solvent, mixing the toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution;
s8, cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr, wherein the total amount of the chlorfenapyr is 10.3kg.
The method for recovering the proline comprises the following steps: and (3) dropwise adding a sodium hydroxide solution into the water phase discharged from the step (S5), stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing for 1 hour at room temperature, centrifugally drying to obtain 7.7kg of proline, and calculating that the recovery rate of the proline is 93.6%, and the detected content is 97.7% and can be repeatedly used.
This comparative example differs from example 1 only in that: the control temperatures during S2, S3 and S4 are all below the protection (limit) range of the present invention.
Comparison results: the yield of chlorfenapyr in this comparative example was 10.3kg, and the yield of chlorfenapyr in example 1 was 11.1kg, whereby it was found that the yield of chlorfenapyr in this comparative example was significantly lower than that in example 1. Indicating that too low a reaction temperature would decrease the yield of chlorfenapyr.
Comparative example 4
The comparative example provides a process for producing chlorfenapyr by taking proline as an acid binding agent, which comprises the following steps:
s1, 10kg of a chlorfenapyr intermediate 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, 7.44kg of diethoxymethane and 26kg of toluene are put into a reaction kettle;
s2, heating the temperature in the reaction kettle to 50 ℃, and stirring for 0.5 hour to enable the substrate to be fully dissolved in toluene as a solvent to obtain a mixed solution;
s3, slowly adding 8.23kg of proline into the reaction kettle, wherein in the process, the temperature of circulating water is reduced, and the temperature in the reaction kettle is controlled to be preferably 50 ℃;
s4, controlling the temperature in the reaction kettle to be 50-55 ℃, and refluxing for 2 hours;
s5, adding 20kg of clear water into the reaction kettle, stirring for 0.5 hour, extracting proline salt, fully dissolving the proline salt in the clear water, standing for 2 hours, layering an organic phase and a water phase, discharging the water phase, and leaving the organic phase in the reaction kettle;
s6, controlling the temperature in the reaction kettle to be kept at 50 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to room temperature of 25 ℃;
s7, mixing toluene and ethanol according to a volume ratio of 1:2 to obtain a toluene-ethanol mixed solvent, mixing the toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution;
s8, cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr, wherein the total amount of the chlorfenapyr is 11.1kg.
The method for recovering the proline comprises the following steps: and (3) dropwise adding a sodium hydroxide solution into the water phase discharged from the step (S5), stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing for 1 hour at room temperature, centrifugally drying to obtain 7.0kg of proline, and calculating that the recovery rate of the proline is 85.1%, and the detected content is 97.5%, so that the proline can be repeatedly used.
This comparative example differs from example 1 only in that: the amount of fresh water added in S5 is below the protection (limit) range of the invention.
Comparison results: the recovery of the acid-binding agent proline in this comparative example was 7.0kg, the recovery was 85.1%, and the recovery of the acid-binding agent proline in example 1 was 7.8kg, and the recovery was 94.8%, which means that the recovery of the acid-binding agent proline in this comparative example was significantly lower than that in example 1. The result shows that too little clear water is used for extraction, which can reduce the recovery rate of the acid-binding agent proline.
The foregoing is a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention and are intended to be comprehended within the scope of the present invention.
Claims (10)
1. A process for preparing chlorfenapyr by using proline as acid-binding agent is characterized in that 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile and diethoxymethane are used as starting materials under the condition of an organic solvent, at least stirring is carried out for 0.5 hour at the temperature of 48-52 ℃ to obtain a mixed solution, then the proline is used as the acid-binding agent, reflux is carried out for 2 hours at the temperature of 50-60 ℃, then clear water is added, stirring is carried out, water phase is discharged after standing, and the rest organic phase is subjected to post treatment to obtain the chlorfenapyr.
2. The process for producing the chlorfenapyr by using the proline as the acid-binding agent according to claim 1, wherein toluene is adopted as the organic solvent, and the molar ratio of the 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-nitrile, the diethoxymethane and the toluene is 1:2.5:9.
3. The process for producing the chlorfenapyr by taking the proline as the acid binding agent according to claim 1, wherein a mixed solution is prepared at the temperature of 50 ℃; controlling the temperature to be 50 ℃, and adding proline into the mixed solution; the reflux temperature was maintained at 50-55 ℃.
4. The process for producing chlorfenapyr using proline as an acid binding agent according to claim 1, wherein the molar ratio of proline to 4-bromo-2- (p-chlorophenyl) -5- (trifluoromethyl) -pyrrole-3-carbonitrile is 2:1.
5. The process for producing the chlorfenapyr by using the proline as the acid binding agent according to claim 1, wherein the mass ratio of the clear water to the mixed solution is (0.6-0.7): 1.
6. The process for producing the chlorfenapyr by taking the proline as the acid binding agent according to claim 1, wherein the specific operation steps of the post-treatment are as follows: controlling the temperature to be 50-60 ℃, carrying out reduced pressure distillation on the organic phase until no fraction exists, obtaining a concentrated organic phase, and cooling to 25-30 ℃; then mixing toluene-ethanol mixed solvent with the concentrated organic phase in equal volume, and uniformly stirring to obtain an organic solution; and then cooling the organic solution to 0-5 ℃, and centrifugally drying to obtain the chlorfenapyr.
7. The process for producing the chlorfenapyr by using the proline as the acid binding agent according to claim 6, wherein the temperature is controlled to be 50 ℃, and the organic phase is distilled under reduced pressure until no fraction exists.
8. The process for producing chlorfenapyr with proline as an acid binding agent according to claim 6, wherein the concentrated organic phase is obtained and cooled to 25 ℃.
9. The process for producing the chlorfenapyr by using the proline as the acid-binding agent according to claim 6, wherein the volume ratio of toluene to ethanol in the toluene-ethanol mixed solvent is 1:2.
10. The process for producing chlorfenapyr by using proline as an acid binding agent according to any one of claims 1 to 9, wherein the recovery method of proline is as follows: and (3) dropwise adding sodium hydroxide solution into the discharged water phase, stirring at the same time, detecting the pH value of the water phase, stopping dropwise adding the sodium hydroxide solution when the pH value of the water phase reaches 6.3, standing at room temperature for 1 hour, and centrifugally drying to obtain the proline.
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