CN114560784A - Method for continuously synthesizing bentazone intermediate anthranilic acid isopropylamide - Google Patents
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- OTTDACPMYLDVTL-UHFFFAOYSA-N ethyl quinoline-3-carboxylate Chemical compound C1=CC=CC2=CC(C(=O)OCC)=CN=C21 OTTDACPMYLDVTL-UHFFFAOYSA-N 0.000 title claims abstract description 34
- ZOMSMJKLGFBRBS-UHFFFAOYSA-N bentazone Chemical compound C1=CC=C2NS(=O)(=O)N(C(C)C)C(=O)C2=C1 ZOMSMJKLGFBRBS-UHFFFAOYSA-N 0.000 title claims abstract description 27
- 238000000034 method Methods 0.000 title claims abstract description 27
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- CNBGNNVCVSKAQZ-UHFFFAOYSA-N benzidamine Natural products C12=CC=CC=C2C(OCCCN(C)C)=NN1CC1=CC=CC=C1 CNBGNNVCVSKAQZ-UHFFFAOYSA-N 0.000 title claims abstract description 24
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- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims abstract description 30
- XKJCHHZQLQNZHY-UHFFFAOYSA-N phthalimide Chemical compound C1=CC=C2C(=O)NC(=O)C2=C1 XKJCHHZQLQNZHY-UHFFFAOYSA-N 0.000 claims abstract description 25
- 239000003513 alkali Substances 0.000 claims abstract description 21
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims abstract description 18
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 claims abstract description 17
- 239000005708 Sodium hypochlorite Substances 0.000 claims abstract description 16
- SUKJFIGYRHOWBL-UHFFFAOYSA-N sodium hypochlorite Chemical compound [Na+].Cl[O-] SUKJFIGYRHOWBL-UHFFFAOYSA-N 0.000 claims abstract description 16
- 238000000605 extraction Methods 0.000 claims abstract description 11
- 238000005191 phase separation Methods 0.000 claims abstract description 3
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- 239000007788 liquid Substances 0.000 claims description 12
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 8
- 239000000460 chlorine Substances 0.000 claims description 8
- 229910052801 chlorine Inorganic materials 0.000 claims description 8
- 239000000463 material Substances 0.000 claims description 8
- 230000035484 reaction time Effects 0.000 claims description 8
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- WMITWVBNOFXTJE-UHFFFAOYSA-N 2-aminobenzoic acid;propan-2-amine Chemical compound CC(C)N.NC1=CC=CC=C1C(O)=O WMITWVBNOFXTJE-UHFFFAOYSA-N 0.000 claims description 7
- 239000012074 organic phase Substances 0.000 claims description 6
- 235000011121 sodium hydroxide Nutrition 0.000 claims description 5
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims 2
- VYFOAVADNIHPTR-UHFFFAOYSA-N isatoic anhydride Chemical compound NC1=CC=CC=C1CO VYFOAVADNIHPTR-UHFFFAOYSA-N 0.000 description 10
- RWZYAGGXGHYGMB-UHFFFAOYSA-N anthranilic acid Chemical compound NC1=CC=CC=C1C(O)=O RWZYAGGXGHYGMB-UHFFFAOYSA-N 0.000 description 4
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- 239000003960 organic solvent Substances 0.000 description 2
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 2
- 239000002994 raw material Substances 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
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- XTHPWXDJESJLNJ-UHFFFAOYSA-N chlorosulfonic acid Substances OS(Cl)(=O)=O XTHPWXDJESJLNJ-UHFFFAOYSA-N 0.000 description 1
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- ZFXYFBGIUFBOJW-UHFFFAOYSA-N theophylline Chemical compound O=C1N(C)C(=O)N(C)C2=C1NC=N2 ZFXYFBGIUFBOJW-UHFFFAOYSA-N 0.000 description 1
- 229960000278 theophylline Drugs 0.000 description 1
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/02—Preparation of carboxylic acid amides from carboxylic acids or from esters, anhydrides, or halides thereof by reaction with ammonia or amines
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D265/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom and one oxygen atom as the only ring hetero atoms
- C07D265/04—1,3-Oxazines; Hydrogenated 1,3-oxazines
- C07D265/12—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems
- C07D265/14—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring
- C07D265/24—1,3-Oxazines; Hydrogenated 1,3-oxazines condensed with carbocyclic rings or ring systems condensed with one six-membered ring with hetero atoms directly attached in positions 2 and 4
- C07D265/26—Two oxygen atoms, e.g. isatoic anhydride
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Indole Compounds (AREA)
Abstract
The invention discloses a method for continuously synthesizing bentazone intermediate anthranilic acid isopropylamide, which comprises the following steps: after being dissolved in alkali, the phthalimide reacts with a precooled sodium hypochlorite solution in a first module of a micro-reaction continuous flow device, hydrochloric acid and dichloroethane solution of isopropylamine are sequentially added into subsequent modules, and the anthranilic acid isopropylamide is obtained through centrifugal extraction and phase separation.
Description
Technical Field
The invention relates to the technical field of pesticide intermediate compounds, in particular to a method for synthesizing a bentazon intermediate anthranilic acid isopropylamide by using a micro-reaction continuous flow device.
Background
Bentazone, also known as bentazone, is a selective contact type broadleaf herbicide for wheat fields, and has the chemical name of 3-isopropyl- (1H) -benzo-2, 1, 3-thiadiazine-4-one-2, 2-dioxide. The herbicide composition has excellent control effect on broad-leaved weeds and cyperaceae weeds, particularly perennial malignant weeds such as cyperus esculentus, cyperus rotundus and Guapian, xanthium and the like, and is safe for crops such as rice, triticale, soybeans, peanuts, corns, sugarcanes, peas and onions.
At present, the preparation process of bentazon mostly adopts an isatoic anhydride method, and comprises the following steps: synthesizing isatoic anhydride; amidating isatoic anhydride and isopropylamine in organic solvent to produce intermediate anthranilic acid isopropylamide; the anthranilic acid isopropylamide is subjected to sulfonation reaction with chlorosulfonic acid and 2-methylpyridine to form a double salt; the compound salt is cyclized under the action of phosphorus oxychloride to obtain the bentazone product.
The synthesis reaction formula for preparing anthranilic acid isopropylamide from phthalimide is as follows:
the prior process for preparing anthranilic acid isopropylamide is an intermittent reaction kettle type synthesis process: the isatoic anhydride is generally synthesized in an aqueous phase medium, and amidation reaction of the isatoic anhydride in an organic solvent is usually carried out only by requiring the isatoic anhydride to be a dry product when synthesizing anthranilic acid isopropylamide, and the isatoic anhydride needs solid-liquid separation and drying dehydration. The Hoffman rearrangement reaction synthesized by isatoic anhydride has strict requirements on conditions, the concentrated decomposition of sodium hypochlorite is easily caused due to the excessively low temperature in the early stage of the reaction, a large amount of byproducts are generated due to the excessively high temperature, the product purity is often low due to unstable process parameters, and the byproduct impurity anthranilic acid and the like also enter the intermediate anthranilic acid isopropylamide, so that the quality of the final product bentazone is unstable.
The technical problem to be solved by the invention is to provide a method for continuously synthesizing the anthranilic acid isopropylamide as the intermediate of the bentazone, wherein the anthranilic acid isopropylamide obtained by the method has high purity, is simple to operate, has few steps and is easy for industrial production.
Disclosure of Invention
Aiming at the defects of the existing production process of the bentazone intermediate anthranilic acid isopropylamide, the invention provides a novel method for continuously, stably, intelligently and efficiently synthesizing the bentazone intermediate anthranilic acid isopropylamide by a micro-reaction continuous flow device, and the following purposes are realized:
1) provides the raw material conversion rate, improves the yield of the anthranilic acid isopropylamide and improves the reaction stability.
2) The continuous flow reaction reduces the back mixing of free alkali in the raw materials and the isatoic anhydride as an intermediate product, and reduces the generation of o-aminobenzoic acid as a by-product.
3) The reaction time is shortened, the operation steps are simplified, and the production efficiency of the anthranilic acid isopropylamide is improved.
In order to achieve the purpose, the technical scheme adopted by the application is as follows:
the process flow is shown in figure 1;
a method for continuously synthesizing bentazone intermediate anthranilic acid isopropylamide is realized by the following device, wherein a micro-reaction continuous flow device is connected with a continuous centrifugal extraction device; the micro-reaction continuous flow device comprises four reaction modules which are connected in series;
a method for continuously synthesizing bentazone intermediate anthranilic acid isopropylamide comprises the following specific steps:
sodium hypochlorite is continuously fed from the first group of modules, and alkali solution of phthalimide, hydrochloric acid and isopropylamine are simultaneously fed from the second group of modules, the third group of modules and the fourth group of modules respectively;
and (3) after the phthalimide is dissolved in alkali, reacting the phthalimide with a precooled sodium hypochlorite solution in a micro-reaction continuous flow device, sequentially adding hydrochloric acid and dichloroethane solution of isopropylamine into a subsequent module, and performing centrifugal extraction and phase separation to obtain the anthranilic acid isopropylamide.
The micro-reaction continuous flow device is a micro-channel reactor, and the forming mode of the micro-channel is not limited to processing modes such as etching, linear cutting, laser punching 3D printing and the like.
Preferably, the heat exchange structure of the micro-reaction continuous flow device is not limited to a single-sided or double-sided plate type heat exchange structure, and can also be in a form of being immersed in heat conduction oil or a cooling medium.
Preferably, the feeding speed of the phthalimide alkali solution is 17.4-17.5 g/min.
Preferably, the mass ratio of the liquid caustic soda, the water and the phthalimide in the phthalimide alkali solution is 3.4-3.5: 10: 4.
Preferably, the feeding speed of the sodium hypochlorite solution is 16.2-24.1 g/min, and the feeding speed of the hydrochloric acid is 2.9-3.4 g/min.
Preferably, the liquid caustic soda is 32% in mass fraction, the effective chlorine content of the sodium hypochlorite is 8-12%, and the hydrochloric acid is 31-37% in mass fraction.
Preferably, the feeding speed of the dichloroethane solution of the isopropylamine is 12.7 to 23.8 g/min.
Preferably, the mass fraction of the isopropylamine in the dichloroethane solution is 8 to 15 percent.
Preferably, the reaction time is 5-10 min.
Preferably, the temperature of the first group of modules, the second group of modules and the third group of modules is-5-0 ℃.
Preferably, the temperature of the fourth group of modules is 72-75 ℃.
The invention provides a method for continuously and efficiently synthesizing anthranilic acid isopropylamide by utilizing a micro-reaction continuous flow device, wherein in the synthesis process, in order to improve the reaction yield, the temperature, the flow and the proportion of materials entering the micro-reaction continuous flow device must be strictly controlled.
The invention has the beneficial effects that: the continuous flow is used for producing the anthranilic acid isopropylamide, the micro-reaction continuous flow device is used for realizing the accurate control of conditions such as reaction temperature and the like, and the reaction conversion rate and the selectivity are improved. The whole reaction process is continuous, the solid-liquid separation and drying of the intermediate product isatoic anhydride are not needed, the degree of integration is high, the field operation is not needed, the reaction process is intrinsically safe, the continuous, efficient and stable production of the anthranilic acid isopropylamide can be realized, the purity of the anthranilic acid isopropylamide is more than 99%, and the comprehensive yield is more than 85%.
In order to further illustrate the present invention, the following examples are provided to describe the synthesis of anthranilic acid isopropylamide, which is an intermediate of bentazone.
Drawings
FIG. 1 is a process flow diagram of the present application.
Detailed Description
Example 1
And selecting a microreactor comprising four groups of reaction modules 1, 2, 3 and 4 which are connected in series in sequence for testing. 24.1g/min of sodium hypochlorite solution with the effective chlorine content of 8 percent is continuously fed from a first group of modules through a conveying device, the precooling temperature is minus 5 ℃, 17.4g/min of prepared phthalimide alkali solution (32 percent of liquid alkali: water: phthalimide is 3.4:10:4) is continuously fed from a second group of modules through the conveying device, 3.3g/min of 31 percent hydrochloric acid is continuously fed from a third group of modules through the conveying device, the mass fraction of dichloroethane solution of isopropylamine is 8 percent, the flow rate is 23.8g/min, the reaction temperature is 73 ℃, the reaction time of the materials in a microreactor is 5min, an organic phase is separated after centrifugal extraction, and is subjected to rotary evaporation to remove dichloroethane, the yield of the isopropylamine anthranilic acid is 86 percent, and the purity is 99.1 percent.
Example 2
And selecting a microreactor comprising four groups of reaction modules 1, 2, 3 and 4 which are connected in series in sequence for testing. 21.9g/min of sodium hypochlorite solution with the effective chlorine content of 8 percent is continuously fed from a first group of modules through a conveying device, the precooling temperature is minus 3 ℃, 17.5g/min (32 percent of liquid caustic soda: water: phthalimide is 3.5:10:4) of prepared phthalimide alkali solution is continuously fed from a second group of modules through the conveying device, 3.4g/min of 31 percent hydrochloric acid is continuously fed from a third group of modules through the conveying device, the mass fraction of dichloroethane solution of isopropylamine is 10 percent, the flow rate is 18.5g/min, the reaction temperature is 74 ℃, the reaction time of the materials in a microreactor is 10min, an organic phase is separated after centrifugal extraction, and is subjected to rotary evaporation to remove dichloroethane, the yield of the isopropylamine anthranilic acid is 86.5 percent, and the purity is 99.2 percent.
Example 3
And selecting a microreactor comprising four groups of reaction modules 1, 2, 3 and 4 which are connected in series in sequence for testing. 16.2g/min of sodium hypochlorite solution with 12 percent of available chlorine content is continuously fed from a first group of modules through a conveying device, the precooling temperature is 0 ℃, 17.5g/min of prepared phthalimide alkali solution (32 percent of liquid alkali: water: phthalimide is 3.5:10:4) is continuously fed from a second group of modules through the conveying device, 2.9g/min of 37 percent hydrochloric acid is continuously fed from a third group of modules through the conveying device, the mass fraction of dichloroethane solution of isopropylamine is 12 percent, the flow rate is 18.5g/min, the fourth group of modules are continuously fed through the conveying device, the reaction temperature is 74 ℃, the reaction time of the materials in a microreactor is 8min, an organic phase is separated after centrifugal extraction, dichloroethane is removed by rotary evaporation, the yield of the isopropylamine anthranilic acid isopropylamide is 87 percent, and the purity is 99.2 percent.
Example 4
And selecting a microreactor comprising four groups of reaction modules 1, 2, 3 and 4 which are connected in series in sequence for testing. 19.5g/min of sodium hypochlorite solution with the effective chlorine content of 10 percent is continuously fed from a first group of modules through a conveying device, the precooling temperature is minus 5 ℃, 17.5g/min of prepared phthalimide alkali solution (32 percent of liquid alkali: water: phthalimide is 3.5:10:4) is continuously fed from a second group of modules through the conveying device, 3.3g/min of 32 percent hydrochloric acid is continuously fed from a third group of modules through the conveying device, the mass fraction of dichloroethane solution of isopropylamine is 11 percent, the flow rate is 23.8g/min, the reaction temperature is 73 ℃, the reaction time of the materials in a microreactor is 5min, an organic phase is separated after centrifugal extraction, and is subjected to rotary evaporation to remove dichloroethane, the yield of the isopropylamine anthranilic acid is 87.2 percent, and the purity is 99.2 percent.
Example 5
And selecting a microreactor comprising four groups of reaction modules 1, 2, 3 and 4 which are connected in series in sequence for testing. 16.4g/min of sodium hypochlorite solution with 12 percent of available chlorine content is continuously fed from a first group of modules through a conveying device, the precooling temperature is minus 5 ℃, 17.5g/min of prepared phthalimide alkali solution (32 percent of liquid alkali: water: phthalimide is 3.5:10:4) is continuously fed from a second group of modules through the conveying device, 3.4g/min of 31 percent hydrochloric acid is continuously fed from a third group of modules through the conveying device, the mass fraction of dichloroethane solution of isopropylamine is 15 percent, the flow rate is 12.7g/min, the materials are continuously fed from a fourth group of modules through the conveying device, the reaction temperature is 75 ℃, the reaction time of the materials in a microreactor is 10min, an organic phase is separated after centrifugal extraction, the dichloroethane is removed, the yield of the isopropylamine anthranilic acid is 85 percent, and the purity is 99.0 percent.
Although the present invention has been described with reference to the specific embodiments, it is not intended to limit the scope of the present invention, and various modifications and variations can be made by those skilled in the art without inventive changes based on the technical solution of the present invention.
Claims (10)
1. A method for continuously synthesizing an anthranilic acid isopropylamide as a bentazone intermediate is characterized by being realized by the following device, wherein a micro-reaction continuous flow device is connected with a continuous centrifugal extraction device; the micro-reaction continuous flow device comprises four reaction modules which are connected in series;
the method for continuously synthesizing the bentazone intermediate anthranilic acid isopropylamide comprises the following specific steps:
continuously feeding sodium hypochlorite from the first group of modules, and continuously feeding an alkali solution of phthalimide, hydrochloric acid and isopropylamine from the second group of modules, the third group of modules and the fourth group of modules respectively;
reacting the alkali solution of phthalimide with the precooled sodium hypochlorite solution in a micro-reaction continuous flow device, sequentially adding hydrochloric acid and dichloroethane solution of isopropylamine into a subsequent module, and performing centrifugal extraction and phase separation to obtain the isopropylamide anthranilate.
2. The method for continuously synthesizing the anthranilic acid isopropylamide as the intermediate of bentazone according to claim 1, wherein the feeding speed of the phthalimide alkali solution is 17.4-17.5 g/min.
The mass ratio of the liquid caustic soda, the water and the phthalimide in the phthalimide alkali solution is 3.4-3.5: 10: 4.
3. The method for continuously synthesizing the anthranilic acid isopropylamide as the intermediate of bentazone according to claim 1, wherein the feeding speed of the sodium hypochlorite solution is 16.2-24.1 g/min, and the feeding speed of the hydrochloric acid is 2.9-3.4 g/min.
4. The method for continuously synthesizing the anthranilic acid isopropylamide as the intermediate of bentazone according to claim 1, wherein the liquid caustic soda comprises 32% by mass, the available chlorine content of the sodium hypochlorite is 8-12% by mass, and the hydrochloric acid comprises 31-37% by mass.
5. The method for continuously synthesizing the isopropylamide anthranilate as a bentazone intermediate of claim 1, wherein the feed rate of the dichloroethane solution of the isopropylamine is 12.7-23.8 g/min.
6. The method for continuously synthesizing the isopropylamine anthranilate as the intermediate of bentazone according to claim 1, wherein the mass fraction of the isopropylamine in the dichloroethane solution is 8-15%.
7. The method for continuously synthesizing the anthranilic acid isopropylamide as the intermediate of bentazone according to claim 1, wherein the reaction time in the microreactor is 5-10 min.
8. The method for continuously synthesizing the anthranilic acid isopropylamide as the intermediate of bentazone according to claim 1, wherein the temperature of the first, second and third groups of modules is preferably-5 to 0 ℃.
9. The method for continuously synthesizing the anthranilic acid isopropylamide as the intermediate of bentazone according to claim 1, wherein the temperature of the fourth module is 72-75 ℃.
10. The method for continuously synthesizing the anthranilic acid isopropylamide as the intermediate of bentazone according to claim 1, which comprises the following steps:
selecting a microreactor comprising four groups of reaction modules 1, 2, 3 and 4 which are connected in series in sequence for testing, continuously feeding 24.1g/min sodium hypochlorite solution with the effective chlorine content of 8% from the first group of modules through a conveying device, precooling the temperature to be 5 ℃ below zero, preparing 17.4g/min phthalimide alkali solution, and preparing 32% liquid alkali by mass fraction: water: phthalimide is 3.4:10:4, continuously fed from the second group of modules through a conveying device, 31% hydrochloric acid is 3.3g/min, ethylene dichloride solution of isopropylamine is 23.8g/min (the ethylene dichloride of the isopropylamine is 1.9:21.9), continuously fed from the fourth group of modules through the conveying device, the reaction temperature is 73 ℃, the materials are reacted in a microreactor for 5min, and organic phase is separated out after centrifugal extraction to spin-evaporate and remove dichloroethane.
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Citations (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP0013900A1 (en) * | 1979-01-26 | 1980-08-06 | BASF Aktiengesellschaft | Process for the continuous production of isatoic anhydride |
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