CN113024479B - Preparation method of clomazone - Google Patents
Preparation method of clomazone Download PDFInfo
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- CN113024479B CN113024479B CN201911344799.5A CN201911344799A CN113024479B CN 113024479 B CN113024479 B CN 113024479B CN 201911344799 A CN201911344799 A CN 201911344799A CN 113024479 B CN113024479 B CN 113024479B
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- 239000005499 Clomazone Substances 0.000 title claims abstract description 12
- KIEDNEWSYUYDSN-UHFFFAOYSA-N clomazone Chemical compound O=C1C(C)(C)CON1CC1=CC=CC=C1Cl KIEDNEWSYUYDSN-UHFFFAOYSA-N 0.000 title claims abstract description 12
- 238000002360 preparation method Methods 0.000 title claims abstract description 11
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims abstract description 84
- 235000011121 sodium hydroxide Nutrition 0.000 claims abstract description 29
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 238000000034 method Methods 0.000 claims abstract description 16
- LOBXXWMXAMOBAH-UHFFFAOYSA-N 3-chloro-n-hydroxy-2,2-dimethylpropanamide Chemical compound ClCC(C)(C)C(=O)NO LOBXXWMXAMOBAH-UHFFFAOYSA-N 0.000 claims abstract description 13
- UUXRXRHXOZHHJV-UHFFFAOYSA-N 4,4-dimethyl-1,2-oxazolidin-3-one Chemical compound CC1(C)CONC1=O UUXRXRHXOZHHJV-UHFFFAOYSA-N 0.000 claims abstract description 12
- 238000005574 benzylation reaction Methods 0.000 claims abstract description 8
- MQZNDDUMJVSIMH-UHFFFAOYSA-N 3-chloro-2,2-dimethylpropanoyl chloride Chemical compound ClCC(C)(C)C(Cl)=O MQZNDDUMJVSIMH-UHFFFAOYSA-N 0.000 claims abstract description 7
- XPQUOARMIYXYKC-UHFFFAOYSA-N 2-(2-chlorophenyl)-4,4,5-trimethyl-1,2-oxazolidin-3-one Chemical compound O=C1C(C)(C)C(C)ON1C1=CC=CC=C1Cl XPQUOARMIYXYKC-UHFFFAOYSA-N 0.000 claims abstract description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 21
- 238000003756 stirring Methods 0.000 claims description 13
- XEZNGIUYQVAUSS-UHFFFAOYSA-N 18-crown-6 Chemical group C1COCCOCCOCCOCCOCCO1 XEZNGIUYQVAUSS-UHFFFAOYSA-N 0.000 claims description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 10
- 238000007363 ring formation reaction Methods 0.000 claims description 9
- 150000003983 crown ethers Chemical class 0.000 claims description 7
- 239000000203 mixture Substances 0.000 claims description 5
- 239000000047 product Substances 0.000 claims description 5
- 150000004292 cyclic ethers Chemical class 0.000 claims description 4
- 238000005915 ammonolysis reaction Methods 0.000 claims description 3
- 230000015572 biosynthetic process Effects 0.000 claims description 3
- 238000003786 synthesis reaction Methods 0.000 claims description 3
- 239000013067 intermediate product Substances 0.000 claims description 2
- 239000007858 starting material Substances 0.000 claims description 2
- 238000006243 chemical reaction Methods 0.000 abstract description 42
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 abstract description 15
- WTDHULULXKLSOZ-UHFFFAOYSA-N Hydroxylamine hydrochloride Chemical compound Cl.ON WTDHULULXKLSOZ-UHFFFAOYSA-N 0.000 abstract description 12
- 239000002904 solvent Substances 0.000 abstract description 8
- 239000002994 raw material Substances 0.000 abstract description 6
- 238000000926 separation method Methods 0.000 abstract description 5
- 238000000746 purification Methods 0.000 abstract description 3
- 238000006555 catalytic reaction Methods 0.000 abstract description 2
- 230000003287 optical effect Effects 0.000 abstract description 2
- 238000011084 recovery Methods 0.000 abstract description 2
- 239000007787 solid Substances 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
- 239000012153 distilled water Substances 0.000 description 8
- 238000004128 high performance liquid chromatography Methods 0.000 description 8
- BASMANVIUSSIIM-UHFFFAOYSA-N 1-chloro-2-(chloromethyl)benzene Chemical compound ClCC1=CC=CC=C1Cl BASMANVIUSSIIM-UHFFFAOYSA-N 0.000 description 4
- FHAHTKCVASMXNX-UHFFFAOYSA-N O=C(CCCCCCCCCCCCCCl)Cl Chemical compound O=C(CCCCCCCCCCCCCCl)Cl FHAHTKCVASMXNX-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000010907 mechanical stirring Methods 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 4
- FPYUJUBAXZAQNL-UHFFFAOYSA-N 2-chlorobenzaldehyde Chemical compound ClC1=CC=CC=C1C=O FPYUJUBAXZAQNL-UHFFFAOYSA-N 0.000 description 3
- ZGBBCGIQIYTCEV-UHFFFAOYSA-N 3-chloro-n-[(2-chlorophenyl)methyl]-n-hydroxy-2,2-dimethylpropanamide Chemical compound ClCC(C)(C)C(=O)N(O)CC1=CC=CC=C1Cl ZGBBCGIQIYTCEV-UHFFFAOYSA-N 0.000 description 2
- 241000196324 Embryophyta Species 0.000 description 2
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 238000009776 industrial production Methods 0.000 description 2
- JGGBOFLSKGGBFT-UHFFFAOYSA-N n-[(2-chlorophenyl)methyl]hydroxylamine Chemical compound ONCC1=CC=CC=C1Cl JGGBOFLSKGGBFT-UHFFFAOYSA-N 0.000 description 2
- 150000002923 oximes Chemical class 0.000 description 2
- FZIVKDWRLLMSEJ-UITAMQMPSA-N (nz)-n-[(2-chlorophenyl)methylidene]hydroxylamine Chemical compound O\N=C/C1=CC=CC=C1Cl FZIVKDWRLLMSEJ-UITAMQMPSA-N 0.000 description 1
- FUOSTELFLYZQCW-UHFFFAOYSA-N 1,2-oxazol-3-one Chemical compound OC=1C=CON=1 FUOSTELFLYZQCW-UHFFFAOYSA-N 0.000 description 1
- DYSKAZARRBXDNT-UHFFFAOYSA-N 3-bromo-2,2-dimethylpropanoyl chloride Chemical compound BrCC(C)(C)C(Cl)=O DYSKAZARRBXDNT-UHFFFAOYSA-N 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 240000003183 Manihot esculenta Species 0.000 description 1
- 235000016735 Manihot esculenta subsp esculenta Nutrition 0.000 description 1
- 244000061176 Nicotiana tabacum Species 0.000 description 1
- 235000002637 Nicotiana tabacum Nutrition 0.000 description 1
- 240000000111 Saccharum officinarum Species 0.000 description 1
- 235000007201 Saccharum officinarum Nutrition 0.000 description 1
- 240000008042 Zea mays Species 0.000 description 1
- 235000005824 Zea mays ssp. parviglumis Nutrition 0.000 description 1
- 235000002017 Zea mays subsp mays Nutrition 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000003513 alkali Substances 0.000 description 1
- 239000003638 chemical reducing agent Substances 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 238000009833 condensation Methods 0.000 description 1
- 230000005494 condensation Effects 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 231100000053 low toxicity Toxicity 0.000 description 1
- 238000006146 oximation reaction Methods 0.000 description 1
- 239000000049 pigment Substances 0.000 description 1
- 238000006722 reduction reaction Methods 0.000 description 1
- 150000003839 salts Chemical class 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
- C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
- C07D261/04—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
-
- 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
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/584—Recycling of catalysts
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Abstract
The invention relates to a preparation method of clomazone. The invention provides a method for preparing 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone by using hydroxylamine hydrochloride as a raw material, dripping chloro pivaloyl chloride under the action of a self-made ether catalyst to obtain an intermediate 3-chloro-N-hydroxy-2, 2-dimethyl propionamide with high yield, and then carrying out benzylation on cyclized 4, 4-dimethyl-3-isoxazolidone under the catalysis of a pioneer tablet base without separation. Compared with the existing literature methods, the method of the invention innovatively uses the self-made ether catalyst, so that the yield of the first step is obviously improved, and the content and the optical purity of the product are high. In the final step of the benzylation reaction, caustic soda flakes are used for improving the yield, water is used as a solvent in the whole reaction process, the cost is low, the recovery and the post-treatment are simple, the reaction is mild, and the intermediate control is simple. The preparation method has the advantages of easily available reaction raw materials, mild reaction, high yield, simple separation and purification, low cost and environment-friendly preparation process.
Description
Technical Field
The invention relates to a novel preparation method of a herbicide clomazone for inhibiting preemergence of pigments, and relates to the fields of oximation, cyclization, condensation and the like.
Background
Clomazone is a high-efficiency, low-toxicity and isoxazolone selective pre-emergence herbicide, is mainly used for preventing and removing broadleaf weeds and gramineous weeds in soybean fields, and can also be used for weeding in cassava, corn, rape, sugarcane and tobacco fields. The preparation methods reported in the literature at present are mainly as follows: the o-chlorobenzaldehyde method mainly uses o-chlorobenzaldehyde as the initial raw material, firstly o-chlorobenzaldehyde and salt
The method comprises the following steps of reacting hydroxylamine acid to generate oxime, reducing the oxime to obtain o-chlorobenzyl hydroxylamine, reacting the o-chlorobenzyl hydroxylamine with 3-chloro-2, 2-dimethylpropionyl chloride to obtain 3-chloro-N- (2-chlorobenzyl) -N-hydroxy-2, 2-dimethylpropionamide, and closing the ring of the 3-chloro-N- (2-chlorobenzyl) -N-hydroxy-2, 2-dimethylpropionamide under the action of alkali to obtain the 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone.
In the method, the reduction reaction of o-chlorobenzaldehyde oxime is difficult to control the product in a hydroxylamine stage, and the yield can only reach 80%. Moreover, a large amount of solvents are used, the purification process of the product is complicated, the price of the reducing agent is high, the cost of the synthetic route is high, and the industrial production cannot be realized.
The other synthesis method is a chloro pivaloyl chloride method, 3-chloro-2, 2-dimethylpropionyl chloride or 3-bromo-2, 2-dimethylpropionyl chloride is used as a raw material, and the synthesis of 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone is finally completed through ammonolysis, cyclization and benzylation. The method is improved by Liuwei Dong, Tang Dexiu and other people, but the yield is not high when 3-chloro-N-hydroxy-2, 2-dimethylpropionamide is synthesized, so that the final reaction yield is improved to a small extent, the treatment steps are complicated, and the method is not suitable for industrial production.
Disclosure of Invention
The invention aims to provide a method which is simple, easy, low in cost and environment-friendly and is suitable for industrially preparing clomazone. Comprises the following steps: the preparation method of clomazone is characterized by comprising the following steps of:
1) 3-chloro-2, 2-dimethylpropionyl chloride is used as a starting material, an intermediate product 3-chloro-N-hydroxy-2, 2-dimethylpropionamide is firstly generated through ammonolysis reaction, and in the synthesis process of the intermediate, an ether catalyst is adopted, wherein the ether catalyst is a mixture of cyclic ether and crown ether:
2) then the intermediate is subjected to cyclization reaction to generate 4, 4-dimethyl-3-isoxazolidone, and the target product 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone is generated through benzylation reaction;
further, the cyclic ether is tetrahydrofuran, the crown ether is 18-crown-6-ether, and the molar ratio of the tetrahydrofuran to the 18-crown-6-ether is 1: 0.1-0.3.
Further, the ether catalyst is prepared by introducing 1/3-2/3 tetrahydrofuran into a reactor, adding 18-crown-6-ether, and adding the rest tetrahydrofuran into the reactor while stirring.
Further, the benzylation reaction uses a caustic soda flake as a catalyst.
The invention has the advantages that: the invention provides a reaction system completely using water as a solvent, wherein hydroxylamine hydrochloride is used as a raw material, chloro pivaloyl chloride is dropwise added under the action of a self-made ether catalyst to obtain an intermediate 3-chloro-N-hydroxy-2, 2-dimethyl propionamide with high yield, and then 4, 4-dimethyl-3-isoxazolone prepared by cyclization is directly benzylated under the catalysis of caustic soda flakes initiated by people without separation to prepare the 2- (2-chlorophenyl) methyl-4, 4-dimethyl-3-isoxazolone. Compared with the existing literature methods, the method of the invention innovatively uses the self-made ether catalyst, so that the yield of the first step is obviously improved, and the content and the optical purity of the product are high. In the final step of the benzylation reaction, caustic soda flakes are used for improving the yield, water is used as a solvent in the whole reaction process, the cost is low, the recovery and the post-treatment are simple, the reaction is mild, and the intermediate control is simple. In conclusion, the preparation method has the advantages of easily available reaction raw materials, mild reaction, high yield, simple separation and purification, low cost, environment-friendly preparation process and good industrial application prospect.
Detailed Description
Example one:
step one, 18.8g (0.26mol) of hydroxylamine hydrochloride and 100ml of distilled water and 2g of self-made ether catalyst are added into a 250ml four-mouth bottle, wherein the crown ether is 18-crown-6-ether, and the molar ratio of tetrahydrofuran to 18-crown-6-ether is 1: 0.2; stirring the mixture in an ice salt bath at (-5-0 ℃) and dropwise adding a 30% NaOH solution to enable the pH value of the solution to reach 7.2. 6ml (0.2mol) of chlorotetradecanoyl chloride was then added dropwise, while a 30% NaOH solution was added dropwise, so that the pH of the system was maintained at 7.2. + -. 0.1. After the dropwise addition is finished within 1.5h, stirring for 3h at room temperature. After the reaction is finished, filtering and drying to obtain a white solid, namely the 3-chloro-N-hydroxy-2, 2-dimethylpropionamide. Content 99.0% (HPLC), yield 95.3%.
Step two:
to a 250ml reaction flask equipped with a pH meter, a constant pressure dropping funnel, a thermometer, and a mechanical stirring device, 15.2g of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide (prepared by the first step) and 55ml of distilled water were added, and stirred vigorously at 45 ℃. 30% NaOH solution is added dropwise until the solid is completely dissolved, at which point the pH is 8.2. The dropwise addition of 30% NaOH solution was continued to pH9.0 and stirring was continued at this temperature for 3h, during which time the pH was maintained at 9.0. + -. 0.1 with additional lye. Then 0.6g of NaOH solid is added, and the reaction is carried out for 18h at the temperature of 20 ℃ to obtain 4, 4-dimethylisoxazol-3-one reaction solution. The reaction solution is not required to be separated and can be directly used for the next reaction. Content 97.2% (HPLC).
The reaction solution (containing 97.2% of 4, 4-dimethylisoxazol-3-one) after the last step of cyclization is heated to 90 ℃, 0.6g of NaOH solid and 0.4g of tetrabutylammonium bromide as a catalyst are added, 16.1g of o-chlorobenzyl chloride is added dropwise, and the dropwise addition is completed within 0.5 h. Keeping the temperature at 90 ℃ for 5 h. After the reaction is finished, cooling to room temperature, extracting for three times by using 30ml of ethyl acetate, and removing the solvent from the oil phase to obtain a light yellow oily substance, namely a clomazone crude product. The yield thereof was found to be 94% and the total yield thereof was found to be 87.1%.
Example two:
step one, 18.8g (0.26mol) of hydroxylamine hydrochloride and 100ml of distilled water and 2g of self-made ether catalyst are added into a 250ml four-mouth bottle, wherein the crown ether is 18-crown-6-ether, and the molar ratio of tetrahydrofuran to 18-crown-6-ether is 1: 0.17; stirring the mixture in an ice salt bath at (-5-0 ℃) and dropwise adding a 50% NaOH solution to enable the pH value of the solution to reach 7.2. 6ml (0.2mol) of chlorotetradecanoyl chloride was then added dropwise, while a 50% NaOH solution was added dropwise, so that the pH of the system was maintained at 7.2. + -. 0.1. After the dropwise addition is finished within 1.5h, stirring for 3h at room temperature. After the reaction is finished, filtering and drying to obtain a white solid, namely the 3-chloro-N-hydroxy-2, 2-dimethylpropionamide. Content 99.0% (HPLC), yield 93.3%.
Step two:
to a 250ml reaction flask equipped with a pH meter, a dropping funnel at constant pressure, a thermometer, and a mechanical stirring device, 15.2g of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide (obtained from the first step) and 55ml of distilled water were added, and vigorously stirred at 45 ℃. 30% NaOH solution is added dropwise until the solid is completely dissolved, at which point the pH is 8.2. The dropwise addition of 50% NaOH solution was continued to pH9.0 and stirring was continued at this temperature for 3h, during which time the pH was maintained at 9.0. + -. 0.1 with additional lye. Then 0.6g of NaOH solid is added, and the reaction is carried out for 20h at the temperature of 20 ℃ to obtain 4, 4-dimethylisoxazol-3-one reaction solution. The reaction solution is not required to be separated and can be directly used for the next reaction. Content 98.2% (HPLC).
The reaction solution (containing 97.2% of 4, 4-dimethylisoxazol-3-one) after the last step of cyclization is heated to 90 ℃, 0.6g of NaOH solid and 0.4g of tetrabutylammonium bromide as a catalyst are added, 16.1g of o-chlorobenzyl chloride is added dropwise, and the dropwise addition is finished within 1 hour. Keeping the temperature at 90 ℃ for 5 h. After the reaction is finished, cooling to room temperature, extracting for three times by using 30ml of ethyl acetate, and removing the solvent from the oil phase to obtain a light yellow oily substance, namely a clomazone crude product. The yield thereof was found to be 89%, and the total yield thereof was found to be 82.7%.
Example three:
step one, 18.8g (0.26mol) of hydroxylamine hydrochloride and 100ml of distilled water and 2g of self-made ether catalyst are added into a 250ml four-mouth bottle, wherein the crown ether is 18-crown-6-ether, and the molar ratio of tetrahydrofuran to 18-crown-6-ether is 1: 0.26; stirring the mixture in an ice salt bath at (-5-0 ℃) and dropwise adding a 30% KOH solution to enable the pH value of the solution to reach 7.2. 6ml (0.2mol) of chlorotetradecanoyl chloride was then added dropwise, while a 30% KOH solution was added dropwise, so that the pH of the system was maintained at 7.2. + -. 0.1. After the dropwise addition is finished within 1.5h, stirring for 3h at room temperature. After the reaction is finished, filtering and drying to obtain a white solid, namely the 3-chloro-N-hydroxy-2, 2-dimethylpropionamide. Content 99.0% (HPLC), yield 94.3%.
Step two:
to a 250ml reaction flask equipped with a pH meter, a constant pressure dropping funnel, a thermometer, and a mechanical stirring device, 15.2g of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide (prepared by the first step) and 55ml of distilled water were added, and stirred vigorously at 45 ℃. 30% NaOH solution is added dropwise until the solid is completely dissolved, at which point the pH is 8.2. The addition of 30% KOH solution was continued to pH9.0 and stirring was continued at this temperature for 3h, during which time the pH was maintained at 9.0. + -. 0.1 with additional lye. Then 0.6g of NaOH solid is added, and the reaction is carried out for 18h at the temperature of 20 ℃ to obtain 4, 4-dimethylisoxazol-3-one reaction solution. The reaction solution is not required to be separated and can be directly used for the next reaction. Content 98.2% (HPLC).
The reaction solution (containing 97.2% of 4, 4-dimethylisoxazol-3-one) after the last step of cyclization is heated to 90 ℃, 0.6g of NaOH solid and 0.4g of tetrabutylammonium bromide as a catalyst are added, 16.1g of o-chlorobenzyl chloride is added dropwise, and the dropwise addition is completed within 1.5 h. Keeping the temperature at 90 ℃ for 5 h. After the reaction is finished, cooling to room temperature, extracting for three times by using 30ml of ethyl acetate, and removing the solvent from the oil phase to obtain a light yellow oily substance, namely a clomazone crude product. The yield thereof was found to be 80% and the total yield thereof was found to be 75.4%.
Example four (comparative):
step one, 18.8g (0.26mol) of hydroxylamine hydrochloride and 100ml of distilled water are added into a 250ml four-mouth bottle, stirred under an ice salt bath (-5-0 ℃) and added with 30% NaOH solution dropwise to enable the pH value of the solution to reach 7.2. 7.8ml (0.26mol) of chlorotetradecanoyl chloride was then added dropwise, while a 30% NaOH solution was added dropwise, so that the pH of the system was maintained at 7.2. + -. 0.1. After the dropwise addition is finished within 1.5h, stirring for 3h at room temperature. After the reaction is finished, filtering and drying to obtain a white solid, namely the 3-chloro-N-hydroxy-2, 2-dimethylpropionamide. Content 85.0% (HPLC), yield 76.7%.
Step two:
to a 250ml reaction flask equipped with a pH meter, a constant pressure dropping funnel, a thermometer, and a mechanical stirring device, 15.2g of 3-chloro-N-hydroxy-2, 2-dimethylpropionamide (prepared by the first step) and 55ml of distilled water were added, and stirred vigorously at 45 ℃. 30% NaOH solution is added dropwise until the solid is completely dissolved, at which point the pH is 8.2. The 30% NaOH solution is continuously added dropwise to pH9.0, and stirring is continued for 3h at this temperature, during which time the pH is maintained at 9.0 + -0.1 with additional lye. Then 0.6g of NaOH solid is added, and the reaction is carried out for 18h at the temperature of 20 ℃ to obtain 4, 4-dimethylisoxazol-3-one reaction solution. The reaction solution was used directly in the next reaction without separation, with a content of 88.6% (HPLC).
The reaction solution (containing 97.2% of 4, 4-dimethylisoxazol-3-one) after the last step of cyclization is heated to 100 ℃, 0.6g of NaOH solid and 0.4g of tetrabutylammonium bromide as a catalyst are added, 16.1g of o-chlorobenzyl chloride is added dropwise, and the dropwise addition is completed within 0.5 h. Keeping the temperature at 90 ℃ for 5 h. After the reaction is finished, cooling to room temperature, extracting for three times by using 30ml of ethyl acetate, removing the solvent from the oil phase to obtain a light yellow oily substance, namely a clomazone crude product, wherein the yield is 81.2 percent, and the total yield is 69.5 percent.
Claims (3)
1. The preparation method of clomazone is characterized by comprising the following steps of:
1) 3-chloro-2, 2-dimethylpropionyl chloride is used as a starting material, an intermediate product 3-chloro-N-hydroxy-2, 2-dimethylpropionamide is firstly generated through ammonolysis reaction, and in the synthesis process of the intermediate, an ether catalyst is adopted, wherein the ether catalyst is a mixture of cyclic ether and crown ether:
2) then the intermediate is subjected to cyclization reaction to generate 4, 4-dimethyl-3-isoxazolidone, and the target product 2- (2-chlorphenyl) methyl-4, 4-dimethyl-3-isoxazolidone is generated through benzylation reaction;
the cyclic ether is tetrahydrofuran, the crown ether is 18-crown-6-ether, and the molar ratio of the tetrahydrofuran to the 18-crown-6-ether is 1: 0.1-0.3.
2. The method of claim 1, wherein the ether catalyst is prepared by introducing 1/3-2/3-tetrahydrofuran into a reactor, adding 18-crown-6-ether, and adding the rest tetrahydrofuran into the reactor while stirring.
3. The method of claim 1, wherein the benzylation reaction is carried out using caustic soda flakes as a catalyst.
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| CN1775765A (en) * | 2005-11-29 | 2006-05-24 | 江苏长青农化股份有限公司 | Method for synthesizing 4, 4-dimethyl-iso-xazole-3-one |
| CN106749072A (en) * | 2016-11-12 | 2017-05-31 | 江苏长青生物科技有限公司 | The preparation method of clomazone |
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| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1775765A (en) * | 2005-11-29 | 2006-05-24 | 江苏长青农化股份有限公司 | Method for synthesizing 4, 4-dimethyl-iso-xazole-3-one |
| CN106749072A (en) * | 2016-11-12 | 2017-05-31 | 江苏长青生物科技有限公司 | The preparation method of clomazone |
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Denomination of invention: A Preparation Method of Isooxazone Granted publication date: 20220603 Pledgee: Guangfa Bank Co.,Ltd. Yangzhou Branch Pledgor: JIANGSU CHANGQING AGROCHEMICAL Co.,Ltd. Registration number: Y2024980003133 |