CN116253696A - Continuous flow preparation method of oxadiazon - Google Patents
Continuous flow preparation method of oxadiazon Download PDFInfo
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- CN116253696A CN116253696A CN202111509607.9A CN202111509607A CN116253696A CN 116253696 A CN116253696 A CN 116253696A CN 202111509607 A CN202111509607 A CN 202111509607A CN 116253696 A CN116253696 A CN 116253696A
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- 239000005588 Oxadiazon Substances 0.000 title claims abstract description 49
- CHNUNORXWHYHNE-UHFFFAOYSA-N Oxadiazon Chemical compound C1=C(Cl)C(OC(C)C)=CC(N2C(OC(=N2)C(C)(C)C)=O)=C1Cl CHNUNORXWHYHNE-UHFFFAOYSA-N 0.000 title claims abstract description 49
- 238000002360 preparation method Methods 0.000 title claims abstract description 22
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims abstract description 66
- GWHQKTAGVTYTJX-UHFFFAOYSA-N (2,4-dichloro-5-propan-2-yloxyphenyl)hydrazine Chemical compound CC(C)OC1=CC(NN)=C(Cl)C=C1Cl GWHQKTAGVTYTJX-UHFFFAOYSA-N 0.000 claims abstract description 28
- 239000003153 chemical reaction reagent Substances 0.000 claims abstract description 25
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims abstract description 23
- 238000006243 chemical reaction Methods 0.000 claims abstract description 20
- JVSFQJZRHXAUGT-UHFFFAOYSA-N 2,2-dimethylpropanoyl chloride Chemical compound CC(C)(C)C(Cl)=O JVSFQJZRHXAUGT-UHFFFAOYSA-N 0.000 claims abstract description 17
- 238000000034 method Methods 0.000 claims abstract description 9
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 29
- 239000000463 material Substances 0.000 claims description 18
- 238000002156 mixing Methods 0.000 claims description 12
- 238000005917 acylation reaction Methods 0.000 claims description 9
- 238000007363 ring formation reaction Methods 0.000 claims description 8
- 239000002904 solvent Substances 0.000 claims description 7
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 6
- 230000035484 reaction time Effects 0.000 claims description 5
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 4
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 2
- CAHQGWAXKLQREW-UHFFFAOYSA-N Benzal chloride Chemical compound ClC(Cl)C1=CC=CC=C1 CAHQGWAXKLQREW-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 238000005112 continuous flow technique Methods 0.000 claims 10
- 229960001701 chloroform Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 abstract description 6
- 239000007788 liquid Substances 0.000 abstract description 3
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
- 239000012074 organic phase Substances 0.000 description 6
- 239000012071 phase Substances 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000005406 washing Methods 0.000 description 5
- 239000002994 raw material Substances 0.000 description 4
- 238000011084 recovery Methods 0.000 description 4
- 239000003513 alkali Substances 0.000 description 3
- 238000004090 dissolution Methods 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 238000010828 elution Methods 0.000 description 3
- 230000002363 herbicidal effect Effects 0.000 description 3
- 239000004009 herbicide Substances 0.000 description 3
- 238000005191 phase separation Methods 0.000 description 3
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
- 230000010933 acylation Effects 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 230000006837 decompression Effects 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 238000005265 energy consumption Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 229940042795 hydrazides for tuberculosis treatment Drugs 0.000 description 2
- 239000007791 liquid phase Substances 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- HKOOXMFOFWEVGF-UHFFFAOYSA-N phenylhydrazine Chemical compound NNC1=CC=CC=C1 HKOOXMFOFWEVGF-UHFFFAOYSA-N 0.000 description 2
- 229940067157 phenylhydrazine Drugs 0.000 description 2
- 238000006722 reduction reaction Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- HFZWRUODUSTPEG-UHFFFAOYSA-N 2,4-dichlorophenol Chemical compound OC1=CC=C(Cl)C=C1Cl HFZWRUODUSTPEG-UHFFFAOYSA-N 0.000 description 1
- 244000105624 Arachis hypogaea Species 0.000 description 1
- NDLJGBNPQPHMBK-UHFFFAOYSA-N C(Cl)(Cl)Cl.ClC1=C(C=C(C(=C1)Cl)OC(C)C)NN Chemical compound C(Cl)(Cl)Cl.ClC1=C(C=C(C(=C1)Cl)OC(C)C)NN NDLJGBNPQPHMBK-UHFFFAOYSA-N 0.000 description 1
- 229920000742 Cotton Polymers 0.000 description 1
- 241000196324 Embryophyta Species 0.000 description 1
- 244000299507 Gossypium hirsutum Species 0.000 description 1
- 241000238631 Hexapoda Species 0.000 description 1
- 229940087098 Oxidase inhibitor Drugs 0.000 description 1
- 108020001991 Protoporphyrinogen Oxidase Proteins 0.000 description 1
- 102000005135 Protoporphyrinogen oxidase Human genes 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 125000002252 acyl group Chemical group 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- 230000009286 beneficial effect Effects 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 230000018044 dehydration Effects 0.000 description 1
- 238000006297 dehydration reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000006193 diazotization reaction Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 238000006266 etherification reaction Methods 0.000 description 1
- 239000012530 fluid Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- 244000144972 livestock Species 0.000 description 1
- 238000006396 nitration reaction Methods 0.000 description 1
- 239000003960 organic solvent Substances 0.000 description 1
- 235000020232 peanut Nutrition 0.000 description 1
- 239000000575 pesticide Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D271/00—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms
- C07D271/02—Heterocyclic compounds containing five-membered rings having two nitrogen atoms and one oxygen atom as the only ring hetero atoms not condensed with other rings
- C07D271/10—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles
- C07D271/113—1,3,4-Oxadiazoles; Hydrogenated 1,3,4-oxadiazoles with oxygen, sulfur or nitrogen atoms, directly attached to ring carbon atoms, the nitrogen atoms not forming part of a nitro radical
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
- B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
- B01J19/0093—Microreactors, e.g. miniaturised or microfabricated reactors
-
- 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)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention provides a continuous flow preparation method of oxadiazon, which comprises the following steps: continuously adding a 2, 4-dichloro-5-isopropoxy phenylhydrazine solution, a triethylamine reagent, a pivaloyl chloride reagent and a triphosgene solution from a feed inlet of an integrated reactor, and continuously obtaining a coarse product of oxadiazon at a discharge outlet of the integrated reactor; separating and purifying the coarse oxadiazon product to obtain the required oxadiazon product; the invention has simple operation and safe and efficient production; the method has higher mass transfer and heat transfer efficiency, low liquid holdup of the reaction system and small volume of the reactor.
Description
Technical Field
The invention relates to the technical field of preparation of pesticide herbicide raw materials, and particularly discloses a preparation method of oxadiazon.
Background
Oxadiazon is a protoporphyrinogen oxidase inhibitor selective pre-bud and post-bud herbicide variety, is mainly used for preventing and killing various annual monocotyledonous and dicotyledonous weeds, is mainly used for weeding in paddy fields, and is also effective for peanuts, cotton, sugarcanes and the like in dry fields; the contact-killing pre-emergence and post-emergence herbicide has the characteristics of high efficiency, long acting, broad spectrum, small dosage, safety to human and livestock and environment, mild to natural enemies and beneficial organisms of insects, and the like, and has wide market prospect.
The current industrial synthesis route of oxadiazon mainly uses 2, 4-dichlorophenol as a raw material, and is obtained through 10 steps of reactions including esterification, nitration, hydrolysis, etherification, reduction, diazotization, secondary reduction, alkalization, acylation and cyclization. The final two steps are to take 2, 4-dichloro-5-isopropoxy phenylhydrazine as raw material, and to obtain oxadiazon product through acylation and cyclization.
At present, the synthetic route mainly adopts an intermittent process to produce oxadiazon, the first step of acylation reaction is completed in a reaction kettle, and pivaloyl chloride and phenylhydrazine are not very stable and react vigorously with each other; in order to ensure production safety, most of the acyl reactions of batch processes are controlled to be carried out at low temperature (for example, 5-15 ℃), and pivaloyl chloride is operated by adopting a mode of temperature control dropwise addition; in addition, in the cyclization reaction of the second step, triphosgene or phosgene is slowly dripped or introduced, the reaction is carried out by controlling the temperature in a sectional way, the use efficiency of triphosgene or phosgene is relatively low, the energy consumption of the production process is increased, the temperature is increased for a plurality of times, the operation is complicated, and the production efficiency is reduced.
Disclosure of Invention
The invention aims to overcome the defects of the prior art, and one of the aims of the invention is to provide a continuous flow preparation method of oxadiazon, which is used for solving the problems of complex preparation process, high energy consumption and low production efficiency of oxadiazon in the prior art.
To achieve the above and other objects, the present invention is achieved by comprising the following technical solutions:
a continuous flow preparation method of oxadiazon, comprising the following steps:
continuously adding a 2, 4-dichloro-5-isopropoxy phenylhydrazine solution, a triethylamine reagent, a pivaloyl chloride reagent and a triphosgene solution from a feed inlet of an integrated reactor, and continuously obtaining a coarse product of oxadiazon at an outlet of the integrated reactor;
and separating and purifying the coarse oxadiazon product to obtain the required oxadiazon product.
Further, the integrated reactor comprises a modular structure of a plurality of temperature zones, each of which independently comprises at least one reactor module and/or a group of reactor modules, preferably a continuous flow microreactor comprising three to fifteen individual fluid modules connected at a time.
Specifically, the 2, 4-dichloro-5-isopropoxy phenylhydrazine solution and the triethylamine reagent are mixed, materials are obtained after complete reaction or incomplete reaction, the materials are subjected to acylation reaction with the pivaloyl chloride reagent to produce corresponding hydrazides, and the hydrazides are mixed with the triphosgene solution and subjected to cyclization reaction to produce corresponding oxadiazon.
Further, the preparation of the continuous flow of oxadiazon is carried out in the integrated reactor comprising a first temperature zone, a second temperature zone, a third temperature zone and a fourth temperature zone, comprising the steps of:
s1, mixing the 2, 4-dichloro-5-isopropoxy phenylhydrazine solution and the triethylamine reagent in a first temperature zone to control the temperature in advance, flowing through the first temperature zone, mixing the material flowing through the first temperature zone and the pivaloyl chloride reagent in a second temperature zone, flowing through the second temperature zone, and completing the acylation reaction in the second temperature zone; and
s2, mixing the triphosgene solution through a third temperature zone to pre-control the temperature, flowing through the third temperature zone, mixing the material flowing through the second temperature zone and the raw material with the pre-control temperature through the third temperature zone in a fourth temperature zone, flowing through the fourth temperature zone, and completing cyclization reaction in the fourth temperature zone to generate oxadiazon.
Further, the temperature of the first temperature zone is-5-40 ℃, the temperature of the second temperature zone is 0-60 ℃, the temperature of the third temperature zone is 20-80 ℃, and the temperature of the fourth temperature zone is 30-100 ℃.
Further, the total reaction time of the integrated reactor is 0.25-30 minutes.
Further, the solvent used in the 2, 4-dichloro-5-isopropoxy phenylhydrazine solution and the triphosgene solution is selected from one of toluene, xylene, dichlorotoluene, dichloroethane, dichloromethane, chloroform and carbon tetrachloride, preferably chloroform.
Further, the concentration of the 2, 4-dichloro-5-isopropoxy phenylhydrazine solution is 10wt% to 70wt%, preferably 30wt% to 60wt%
Further, the triphosgene solution concentration is 10wt% to 60wt%, preferably 20wt% to 50wt%.
Further, the molar ratio of the 2, 4-dichloro-5-isopropoxy phenylhydrazine to the triethylamine reagent is 1:1-3.
Further, the molar ratio of the 2, 4-dichloro-5-isopropoxy phenylhydrazine to the pivaloyl chloride reagent is 1:1-1.5.
Further, the molar ratio of the 2, 4-dichloro-5-isopropoxy phenylhydrazine to the triphosgene is 1:0.4-1.
In summary, the invention provides a continuous flow preparation method of oxadiazon, which is simple to operate and safe and efficient to produce compared with the existing kettle type process; the method has higher mass transfer and heat transfer efficiency, the liquid holdup of the reaction system is low, the volume of the reactor is small, the reaction time is shortened to a few minutes or even tens of seconds from the traditional hours, and the reaction efficiency is greatly improved. Other features, benefits and advantages will be apparent from the text disclosure, including the description and claims, detailed herein.
Drawings
Fig. 1 is a process flow diagram of the present invention.
Detailed Description
The invention is further illustrated below in connection with specific examples, which are to be understood as being illustrative of the invention and not limiting the scope of the invention.
The following specific examples are presented to illustrate the present invention, and those skilled in the art will readily appreciate the additional advantages and capabilities of the present invention as disclosed herein. The invention may be practiced or carried out in other embodiments that depart from the specific details, and the details of the present description may be modified or varied from the spirit and scope of the present invention.
The integrated reactor according to the invention may for example be a continuous flow microreactor comprising for example four temperature zones, each of which independently comprises at least one reactor module, which reactor modules are connected in series and/or in parallel and which are connected to each other.
As shown in fig. 1, 2, 4-dichloro-5-isopropoxy phenylhydrazine solution with the concentration of 10 to 70 weight percent and triethylamine reagent are respectively introduced into a precooling module of a continuous flow microreactor from a 2, 4-dichloro-5-isopropoxy phenylhydrazine solution inlet and a triethylamine reagent inlet for mixing reaction in a first temperature zone, materials flowing through the first temperature zone and pivaloyl chloride reagent are mixed in a second temperature zone, the materials flow through the second temperature zone, acylation reaction is completed in the second temperature zone to generate a hydrazide intermediate, triphosgene solution with the concentration of 10 to 60 weight percent is introduced into a third temperature zone from a triphosgene solution inlet for preheating, the materials flowing through the second temperature zone and materials with the temperature pre-controlled by the third temperature zone are mixed in a fourth temperature zone, cyclization reaction is completed in the fourth temperature zone, and oxadiazon solution is generated and discharged from a discharge port of the continuous flow microreactor;
after the oxadiazon solution is discharged from the continuous flow microreactor, hydrochloric acid is added into the oxadiazon solution for washing and phase separation, and a water phase enters a triethylamine recovery section for alkali elution and dissolution to recover a triethylamine solvent; washing the organic phase with water to separate phases, collecting the organic phase for decompression desolventizing to obtain oxadiazon product, and recycling the desolventized and collected organic solvent.
Optionally, the temperature of the first temperature region is-5-40 ℃, for example, can be 0-15 ℃; specifically, for example, it may be 10 ℃; the temperature of the second temperature zone is 0-60 ℃, for example, can be 5-30 ℃; the temperature of the third temperature zone is 20-80 ℃, for example, 30-50 ℃; the temperature in the fourth temperature range is 30 to 100 ℃, for example, 35 to 60 ℃.
Optionally, the molar ratio of the 2, 4-dichloro-5-isopropoxy phenylhydrazine, the triethylamine reagent, the pivaloyl chloride reagent and the triphosgene is 1:1-3: 1 to 1.5:0.4 to 1, for example, 1:1.1 to 1.5:1.05 to 1.3:0.4 to 0.7.
Further, the total reaction time of the continuous flow microreactor may be 0.25 to 30 minutes, for example, 0.25 to 5 minutes.
Example 1
Introducing a 45wt% concentration 2, 4-dichloro-5-isopropoxy phenylhydrazine chloroform solution and a triethylamine reagent into a first temperature zone to be mixed and reacted completely or incompletely to obtain a material, mixing the material flowing through the first temperature zone with a pivaloyl chloride reagent in a second temperature zone, flowing through the second temperature zone to complete an acylation reaction to generate a hydrazide intermediate, introducing a 40wt% concentration triphosgene chloroform solution into a third temperature zone to be preheated; mixing a hydrazide intermediate flowing through a second temperature zone and a triphosgene chloroform solution with a temperature controlled in advance through a third temperature zone in a fourth temperature zone, and flowing through the fourth temperature zone to complete cyclization reaction in the fourth temperature zone to generate oxadiazon chloroform solution;
after the oxadiazon chloroform solution is discharged from the continuous flow microreactor, hydrochloric acid is added into the oxadiazon chloroform solution for washing and phase separation, and an upper water phase enters a triethylamine recovery section for alkali elution, dissolution and recovery of a triethylamine solvent; washing the lower chloroform organic phase with water to separate phases, collecting the lower chloroform organic phase, and performing reduced pressure desolventizing to obtain oxadiazon product, wherein the desolventized and collected chloroform solvent is recycled.
The reaction parameters and results are shown in table 1 below:
wherein T1-T4 respectively represent the temperatures of the first temperature zone, the second temperature zone, the third temperature zone and the fourth temperature zone; the residence time is the total time of flow through the second temperature zone and the fourth temperature zone; the material proportion is the mole proportion of 2, 4-dichloro-5-isopropoxy phenylhydrazine, triethylamine, pivaloyl chloride and triphosgene; phenylhydrazine represents 2, 4-dichloro-5-isopropoxy phenylhydrazine; the product yield was that of oxadiazon.
TABLE 1
The results show that the product yield is better when the temperature of the second temperature zone is 10 ℃ and the temperature of the fourth temperature zone is 50 ℃.
Example 2
The material residence time was screened compared to example 1;
the reaction parameters and results are shown in table 2 below:
TABLE 2
The results show that the product yields are relatively good within the above residence time range.
Example 3
The material ratios were screened compared to example 1;
the reaction parameters and results are shown in table 3 below:
TABLE 3 Table 3
The result shows that the effect is better when the molar ratio of the 2, 4-dichloro-5-isopropoxy phenylhydrazine to the triethylamine is 1:1.6; when the molar ratio of the 2, 4-dichloro-5-isopropoxy phenylhydrazine to the pivaloyl chloride is 1:1.2, the effect is better; the effect is better when the molar ratio of the 2, 4-dichloro-5-isopropoxy phenylhydrazine to the triphosgene is 1:0.5.
Comparative example
Adding 112.5 g of 2, 4-dichloro-5-isopropoxyphenylhydrazine and 112.5 g of chloroform solvent into a 500ml four-neck flask, mixing, stirring and dissolving, cooling to about 5 ℃, adding 87 g of triethylamine to ensure the PH of the system to be more than 8, stirring for half an hour, then dropwise adding 69 g of pivaloyl chloride at 5-20 ℃, ending the dropwise adding, and keeping the temperature and stirring for reaction until the residual of the 2, 4-dichloro-5-isopropoxyphenylhydrazine is less than 0.5% in a liquid phase detection mode;
after the reaction is finished, heating up, carrying out reflux dehydration through a water separator until no water is separated out from the water separator, slowly dropwise adding a chloroform solution of triphosgene at the temperature of below 45 ℃, controlling the temperature to be below 55 ℃, keeping the temperature at 55 ℃ after the dropwise adding is finished, stirring for 1 hour, heating up to 65 ℃ and refluxing for 3 hours until the liquid phase detection hydrazide residue is less than 0.5%;
after the reaction is finished, cooling to room temperature, adding hydrochloric acid, stirring and layering an upper water phase, entering a triethylamine recovery section, and performing alkali elution and dissolution to recover a triethylamine solvent; washing the lower chloroform organic phase with water for phase separation, collecting the lower chloroform organic phase for decompression desolventizing to obtain coarse oxadiazon product with total product yield of 95.6%.
In conclusion, compared with the existing kettle type process, the method is simple to operate, and safe and efficient in production; the method has higher mass transfer and heat transfer efficiency, the liquid holdup of the reaction system is low, the volume of the reactor is small, the reaction time is shortened to a few minutes or even tens of seconds from the traditional hours, and the reaction efficiency is greatly improved.
The above embodiments are merely illustrative of the principles of the present invention and its effectiveness, and are not intended to limit the invention. Modifications and variations may be made to the above-described embodiments by those skilled in the art without departing from the spirit and scope of the invention. Accordingly, it is intended that all equivalent modifications and variations of the invention be covered by the claims, which are within the ordinary skill of the art, be within the spirit and scope of the present disclosure.
Claims (12)
1. A continuous flow process for the preparation of oxadiazon comprising the steps of:
continuously adding a 2, 4-dichloro-5-isopropoxy phenylhydrazine solution, a triethylamine reagent, a pivaloyl chloride reagent and a triphosgene solution into an integrated reactor, and continuously obtaining a coarse product of oxadiazon at a discharge port of the integrated reactor; and
and separating and purifying the coarse oxadiazon product to obtain the required oxadiazon product.
2. The method for preparing oxadiazon according to claim 1, wherein: the integrated reactor comprises a modular structure of a plurality of temperature zones, each of which independently comprises at least one reactor module and/or a group of reactor modules.
3. The continuous flow preparation method of oxadiazon according to claim 1, wherein said 2, 4-dichloro-5-isopropoxy phenylhydrazine solution is mixed with said triethylamine reagent to obtain a material after complete reaction or incomplete reaction, said material is subjected to acylation reaction with said pivaloyl chloride reagent to produce the corresponding hydrazide, and said hydrazide is mixed with said triphosgene solution and cyclized to produce the corresponding oxadiazon.
4. The continuous flow process for the preparation of oxadiazon according to claim 1, characterized in that said continuous flow of oxadiazon preparation is carried out in said integrated reactor comprising a first temperature zone, a second temperature zone, a third temperature zone and a fourth temperature zone, comprising the steps of:
mixing the 2, 4-dichloro-5-isopropoxy phenylhydrazine solution and the triethylamine reagent in a first temperature zone to pre-control the temperature, flowing through the first temperature zone, mixing the material flowing through the first temperature zone and the pivaloyl chloride reagent in a second temperature zone, flowing through the second temperature zone, and completing the acylation reaction in the second temperature zone; and
mixing the triphosgene solution through a third temperature zone to pre-control the temperature, flowing through the third temperature zone, mixing the material flowing through the second temperature zone and the material with the pre-control temperature through the third temperature zone in a fourth temperature zone, flowing through the fourth temperature zone, and completing cyclization reaction in the fourth temperature zone to generate oxadiazon.
5. The continuous flow process for the preparation of oxadiazon according to claim 2, characterized in that: the integrated reactor comprises four temperature areas, namely a first temperature area, a second temperature area, a third temperature area and a fourth temperature area, wherein the temperature of the first temperature area is-5-40 ℃, the temperature of the second temperature area is 0-60 ℃, the temperature of the third temperature area is 20-80 ℃, and the temperature of the fourth temperature area is 30-100 ℃.
6. A continuous flow process for the preparation of oxadiazon according to claim 3, characterized in that: the total reaction time of the integrated reactor is 0.25-30 minutes.
7. The continuous flow process for the preparation of oxadiazon according to claim 1, characterized in that: the solvent used in the 2, 4-dichloro-5-isopropoxy phenylhydrazine solution and the triphosgene solution is selected from one of toluene, xylene, dichlorotoluene, dichloroethane, dichloromethane, trichloromethane and carbon tetrachloride.
8. The continuous flow process for the preparation of oxadiazon according to claim 1, characterized in that: the concentration of the 2, 4-dichloro-5-isopropoxy phenylhydrazine solution is 10 to 70 weight percent.
9. The continuous flow process for the preparation of oxadiazon according to claim 1, characterized in that: the concentration of the triphosgene solution is 10-60 wt%.
10. The continuous flow process for the preparation of oxadiazon according to claim 1, characterized in that: the molar ratio of the 2, 4-dichloro-5-isopropoxy phenylhydrazine to the triethylamine reagent is 1:1-3.
11. The continuous flow process for the preparation of oxadiazon according to claim 1, characterized in that: the molar ratio of the 2, 4-dichloro-5-isopropoxy phenylhydrazine to the pivaloyl chloride reagent is 1:1-1.5.
12. The continuous flow process for the preparation of oxadiazon according to claim 1, characterized in that: the molar ratio of the 2, 4-dichloro-5-isopropoxy phenylhydrazine to the triphosgene is 1:0.4-1.
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Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104327010A (en) * | 2014-09-25 | 2015-02-04 | 合肥星宇化学有限责任公司 | Synthesis technology of oxadiazon |
| CN106336385A (en) * | 2016-08-25 | 2017-01-18 | 江苏丰华化学工业有限公司 | Oxadiazon synthesis method |
| CN110655477A (en) * | 2019-10-25 | 2020-01-07 | 湖南兴同化学科技有限公司 | Synthesis method of oxadiazon intermediate |
| US20210032243A1 (en) * | 2018-02-07 | 2021-02-04 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Continuous process for the preparation of trazodone |
-
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Patent Citations (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN104327010A (en) * | 2014-09-25 | 2015-02-04 | 合肥星宇化学有限责任公司 | Synthesis technology of oxadiazon |
| CN106336385A (en) * | 2016-08-25 | 2017-01-18 | 江苏丰华化学工业有限公司 | Oxadiazon synthesis method |
| US20210032243A1 (en) * | 2018-02-07 | 2021-02-04 | Aziende Chimiche Riunite Angelini Francesco A.C.R.A.F. S.P.A. | Continuous process for the preparation of trazodone |
| CN110655477A (en) * | 2019-10-25 | 2020-01-07 | 湖南兴同化学科技有限公司 | Synthesis method of oxadiazon intermediate |
Non-Patent Citations (2)
| Title |
|---|
| 刘冰 等: "微通道技术在精细化学品合成中的应用", 《染料与染色》, vol. 55, no. 6, 31 December 2018 (2018-12-31), pages 44 - 49 * |
| 陈芬儿 等: "连续流微反应技术在药物合成中的应用研究进展", 《化工进展》, vol. 38, no. 1, 31 December 2019 (2019-12-31), pages 556 - 575 * |
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