CN116041200B - Method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide - Google Patents
Method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide Download PDFInfo
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- CN116041200B CN116041200B CN202211646530.4A CN202211646530A CN116041200B CN 116041200 B CN116041200 B CN 116041200B CN 202211646530 A CN202211646530 A CN 202211646530A CN 116041200 B CN116041200 B CN 116041200B
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- 238000000034 method Methods 0.000 title claims abstract description 28
- KRZCOLNOCZKSDF-UHFFFAOYSA-N 4-fluoroaniline Chemical compound NC1=CC=C(F)C=C1 KRZCOLNOCZKSDF-UHFFFAOYSA-N 0.000 title claims abstract description 25
- 230000002194 synthesizing effect Effects 0.000 title claims description 11
- 239000003054 catalyst Substances 0.000 claims abstract description 40
- 239000007787 solid Substances 0.000 claims abstract description 30
- 238000006243 chemical reaction Methods 0.000 claims abstract description 29
- BKSIERMKNBPHJD-UHFFFAOYSA-N 2-chloro-n-(4-fluorophenyl)-n-propan-2-ylacetamide Chemical compound ClCC(=O)N(C(C)C)C1=CC=C(F)C=C1 BKSIERMKNBPHJD-UHFFFAOYSA-N 0.000 claims abstract description 8
- RMXBOQCXULAXBO-UHFFFAOYSA-N 4-fluoro-n-propan-2-ylaniline Chemical compound CC(C)NC1=CC=C(F)C=C1 RMXBOQCXULAXBO-UHFFFAOYSA-N 0.000 claims abstract description 7
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 22
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 16
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 13
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 11
- VGCXGMAHQTYDJK-UHFFFAOYSA-N Chloroacetyl chloride Chemical compound ClCC(Cl)=O VGCXGMAHQTYDJK-UHFFFAOYSA-N 0.000 claims description 9
- 239000000243 solution Substances 0.000 claims description 9
- 239000011259 mixed solution Substances 0.000 claims description 8
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 8
- 239000007795 chemical reaction product Substances 0.000 claims description 7
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 6
- 239000007788 liquid Substances 0.000 claims description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims description 6
- 229910052757 nitrogen Inorganic materials 0.000 claims description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 4
- 239000012295 chemical reaction liquid Substances 0.000 claims description 4
- 238000001816 cooling Methods 0.000 claims description 4
- 238000011049 filling Methods 0.000 claims description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 4
- 229910000027 potassium carbonate Inorganic materials 0.000 claims description 3
- 238000002156 mixing Methods 0.000 claims description 2
- 239000002904 solvent Substances 0.000 abstract description 6
- 239000002351 wastewater Substances 0.000 abstract description 5
- 238000002360 preparation method Methods 0.000 abstract description 4
- 238000003786 synthesis reaction Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 230000000694 effects Effects 0.000 abstract description 3
- 239000000543 intermediate Substances 0.000 abstract description 3
- 238000001308 synthesis method Methods 0.000 abstract description 3
- 231100000053 low toxicity Toxicity 0.000 abstract description 2
- 239000000575 pesticide Substances 0.000 abstract description 2
- 230000021736 acetylation Effects 0.000 abstract 1
- 238000006640 acetylation reaction Methods 0.000 abstract 1
- 239000007858 starting material Substances 0.000 abstract 1
- 239000002585 base Substances 0.000 description 26
- 230000007062 hydrolysis Effects 0.000 description 8
- 238000006460 hydrolysis reaction Methods 0.000 description 8
- 239000002994 raw material Substances 0.000 description 8
- 239000005531 Flufenacet Substances 0.000 description 5
- IANUJLZYFUDJIH-UHFFFAOYSA-N flufenacet Chemical compound C=1C=C(F)C=CC=1N(C(C)C)C(=O)COC1=NN=C(C(F)(F)F)S1 IANUJLZYFUDJIH-UHFFFAOYSA-N 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 241000196324 Embryophyta Species 0.000 description 4
- 229940126062 Compound A Drugs 0.000 description 3
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 3
- 239000004280 Sodium formate Substances 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 150000001875 compounds Chemical class 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- 239000007789 gas Substances 0.000 description 3
- 238000005470 impregnation Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000010992 reflux Methods 0.000 description 3
- HLBBKKJFGFRGMU-UHFFFAOYSA-M sodium formate Chemical compound [Na+].[O-]C=O HLBBKKJFGFRGMU-UHFFFAOYSA-M 0.000 description 3
- 235000019254 sodium formate Nutrition 0.000 description 3
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 2
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 2
- 230000006978 adaptation Effects 0.000 description 2
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 2
- VXIVSQZSERGHQP-UHFFFAOYSA-N chloroacetamide Chemical compound NC(=O)CCl VXIVSQZSERGHQP-UHFFFAOYSA-N 0.000 description 2
- 238000010835 comparative analysis Methods 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 238000011161 development Methods 0.000 description 2
- 238000010931 ester hydrolysis Methods 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 230000002363 herbicidal effect Effects 0.000 description 2
- 239000004009 herbicide Substances 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 2
- 238000012986 modification Methods 0.000 description 2
- 230000004048 modification Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 1
- 125000006414 CCl Chemical group ClC* 0.000 description 1
- 244000068988 Glycine max Species 0.000 description 1
- 235000010469 Glycine max Nutrition 0.000 description 1
- 240000005979 Hordeum vulgare Species 0.000 description 1
- 235000007340 Hordeum vulgare Nutrition 0.000 description 1
- 241000209082 Lolium Species 0.000 description 1
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 1
- 241000209140 Triticum Species 0.000 description 1
- 235000021307 Triticum 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
- 229910052783 alkali metal Inorganic materials 0.000 description 1
- 150000001340 alkali metals Chemical class 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- 239000000010 aprotic solvent Substances 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- -1 aryloxy acetamide compound Chemical class 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 150000007942 carboxylates Chemical class 0.000 description 1
- 230000032823 cell division Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 235000005822 corn Nutrition 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 230000032050 esterification Effects 0.000 description 1
- 238000005886 esterification reaction Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- IDGUHHHQCWSQLU-UHFFFAOYSA-N ethanol;hydrate Chemical compound O.CCO IDGUHHHQCWSQLU-UHFFFAOYSA-N 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 235000019253 formic acid Nutrition 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- XIGAUIHYSDTJHW-UHFFFAOYSA-N mefenacet Chemical compound N=1C2=CC=CC=C2SC=1OCC(=O)N(C)C1=CC=CC=C1 XIGAUIHYSDTJHW-UHFFFAOYSA-N 0.000 description 1
- GBMDVOWEEQVZKZ-UHFFFAOYSA-N methanol;hydrate Chemical compound O.OC GBMDVOWEEQVZKZ-UHFFFAOYSA-N 0.000 description 1
- 239000000203 mixture Substances 0.000 description 1
- 230000003472 neutralizing effect Effects 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- XTUSEBKMEQERQV-UHFFFAOYSA-N propan-2-ol;hydrate Chemical compound O.CC(C)O XTUSEBKMEQERQV-UHFFFAOYSA-N 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 230000036632 reaction speed Effects 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
- 238000010998 test method Methods 0.000 description 1
- DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
- 238000005809 transesterification reaction Methods 0.000 description 1
- 238000009333 weeding Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- 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
-
- 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
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The invention discloses a synthesis method of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide, and belongs to the technical field of pesticide intermediates. 2-chloro-N- (4-fluorophenyl) -N-isopropyl acetamide is synthesized by acetylation by using 4-fluoro-N-isopropylaniline as a starting material, and then the N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide is obtained by reacting with a solid base catalyst through a trickle bed reactor. The invention solves the problems of large amount of high-salt wastewater, difficult control of reaction, low yield, large solvent amount and the like in the existing synthesis process of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetyl, and also provides a preparation method of the solid base catalyst with high activity, low toxicity, low price, easy obtainment, simple process flow, high yield and high product purity.
Description
Technical Field
The invention belongs to the technical field of pesticide intermediates, and particularly relates to a synthesis method of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide and implementation of a solid base catalyst.
Background
The flufenacet is a herbicide variety, the active component of the flufenacet belongs to an aryloxy acetamide compound which is the same as that of the mefenacet, and the flufenacet has a similar weed control spectrum with a chloroacetamide herbicide, and the flufenacet has the function of mainly inhibiting cell division, and is mainly used for weeding annual gramineous weeds such as ryegrass multiflora and early-stage pre-emergence and post-emergence weeds of certain broadleaf weeds in crop fields such as corn, wheat, barley, soybean and the like.
N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide is an important raw material for synthesizing flufenacet, most of the first steps of the current synthetic route of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide are to dropwise add chloroacetyl chloride into aniline for chloroacetylation, and the steps are simple to operate, high in reaction speed and high in conversion degree. In the second step, the halogenated hydrocarbon hydrolysis and the amide hydrolysis compete, so that two common hydrolysis modes exist, and the first method is as described in patent US5631403A, namely, the hydrolysis is directly carried out by using weak base such as sodium carbonate under a specific solvent, or else, the hydrolysis cannot be carried out; the second is the substitution esterification of C-Cl with a carboxylate followed by ester hydrolysis or transesterification, as described in patent US 5808152A. The first hydrolysis mode needs a large amount of polar high-boiling aprotic solvents, the solvent recovery rate is low, the post-treatment distillation reaction temperature is high, more impurities are generated, recrystallization and purification are difficult, and the product yield is low; the second hydrolysis mode can generate a large amount of high-salt wastewater in the experimental process, the reaction is easy to terminate, the heating speed is precisely controlled in the water removal process, the chloroacetamide intermediate is not thoroughly reacted due to the too fast heating, the product is required to be recrystallized and purified after being mixed, the operation is complicated, and the difficulty is high.
In order to meet the production requirements, development and development of an efficient method for preparing N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide by adopting a solid base catalyst and a trickle bed reactor are still necessary.
Disclosure of Invention
The invention aims to provide a method for preparing N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide by adopting a solid base catalyst matched with a trickle bed reactor, which solves the problems of large amount of high-salt wastewater, difficult reaction control, low yield, large solvent amount and the like in the current synthesis process of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetyl, and also provides a preparation method of the solid base catalyst with high activity, low toxicity, low cost and easy obtainment.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows: a method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide, the method comprising the steps of:
a: mixing 4-fluoro-N-isopropylaniline, sodium carbonate and water, and dropwise adding chloroacetyl chloride to obtain 2-chloro-N- (4-fluorophenyl) -N-isopropyl acetamide;
B: filling a solid base catalyst into a trickle bed reactor to form a stacked bed; the pressure of the reaction system is 1-1.2MPa, and nitrogen enters a trickle bed reactor; dissolving 2-chloro-N- (4-fluorophenyl) -N-isopropyl acetamide in an alcohol-water mixed solution, introducing the solution from the upper end of a trickle bed reactor, contacting the solution with a solid base catalyst from top to bottom, and flowing out a reaction product from the lower end of the trickle bed reactor; and cooling the reaction product, separating by a gas-liquid separator, and crystallizing at a low temperature to obtain the N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide. The reaction equation is expressed as follows:
Further, in the technical scheme, the temperature of dropwise adding the chloracetyl chloride in the step A is 15-45 ℃.
Further, in the technical scheme, the temperature of dropwise adding the chloracetyl chloride in the step A is 25-30 ℃.
Further, in the above technical scheme, the solid base catalyst in the step B is a solid base catalyst such as KF/MgO, KF/CaO, KF/BaO, K 2CO3/MgO、K2CO3/CaO、K2CO3/BaO, etc.
Further, in the above technical scheme, the solid base catalyst in the step B is preferably KF/MgO.
Further, in the above technical scheme, the catalyst filling height in the step B is 6-10cm.
Further, in the above technical scheme, the nitrogen line speed in the step B is 0.1-0.3 m/s.
Further, in the above technical scheme, the nitrogen line speed in the step B is preferably 0.15-0.25 m/s.
Further, in the above technical scheme, the reaction temperature in the step B is 80-140 ℃.
Further, in the above technical scheme, the reaction temperature in the step B is 120 to 130 ℃.
Further, in the above technical scheme, the alcohol in the step B is one or more of methanol, ethanol, n-propanol and isopropanol.
Further, in the above technical scheme, the mass ratio of the 2-chloro-N- (4-fluorophenyl) -N-isopropyl acetamide to the alcohol-water mixed solution in the step B is 0.1-1: 1, a step of; in the alcohol-water mixed solution, the mass ratio of the alcohol to the water is 0.5-1.5: 1.
Further, in the above technical scheme, the mass ratio of the 2-chloro-N- (4-fluorophenyl) -N-isopropyl acetamide to the alcohol-water mixed solution in the step B is preferably 0.3-0.5: 1, a step of; in the alcohol-water mixed solution, the mass ratio of alcohol to water is preferably 1:1.
Further, in the above technical scheme, the reaction solution in the step B is contacted with the catalyst reaction center from top to bottom at a flow rate of 4-6mL/min for reaction.
Advantageous effects of the invention
(1) The catalyst and the synthesis method thereof provided by the invention can be widely applied to the synthesis of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide, and have good universality. The synthesized N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide has higher yield and purity, and can obviously improve the economic benefit of enterprises.
(2) The solid base catalyst of the invention is effective substance of alkali metal, which can provide alkalinity in the synthesis reaction of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide to promote the generation of alkaline hydrolysis reaction. Experiments prove that the method can avoid the defects of the two methods described in the background technology, effectively reduce the use amount of the solvent, greatly reduce the generation of high-salt wastewater, has mild reaction conditions, simple operation and low cost, can achieve 97 percent of product yield and 99.4 percent of content, and is more suitable for mass production.
Detailed Description
The following non-limiting examples will enable those of ordinary skill in the art to more fully understand the invention and are not intended to limit the invention in any way.
The test methods described in the following examples, unless otherwise specified, are all conventional; the reagents and materials, unless otherwise specified, are commercially available.
Example 1
The N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide is synthesized by adopting a KF/MgO solid base catalyst, and the steps are as follows:
(1) 500g of 4-fluoro-N-isopropylaniline, 110g of sodium carbonate and 400g of water are added into a 2L reaction kettle in sequence and stirred uniformly. 220g of chloroacetyl chloride is added dropwise at the speed of 150g/h under the temperature of 25-30 ℃ to ensure that the temperature can not exceed 30 ℃ all the time. Stirring is continued for 1h after the dripping is completed. Standing for layering, and taking the upper layer as the compound A.
(2) The solid base catalyst is synthesized by an impregnation method: the carrier KF is dissolved in deionized water, the carrier MgO is added into the solution, and the mass ratio of KF to MgO is 0.3:1, stirring for 10 hours at room temperature, evaporating and drying at 90 ℃ to obtain a white powdery precursor, and roasting at 600 ℃ for 6 hours to obtain the solid base catalyst KF/MgO.
(3) Compound a was pre-dissolved in 50% isopropyl alcohol-water solution with a mass ratio of 0.33:1, taking the catalyst as a reaction raw material; 14.5g of KF/MgO solid base catalyst was packed in the constant temperature section of the trickle bed reactor to form a packed bed layer having a height of 8 cm. The gas pressure of the reaction system is 1MPa, the nitrogen gas is at the linear speed of 0.22m/s, the reaction center temperature is at 128 ℃, the reaction raw material is introduced from the upper end of the trickle bed reactor at the speed of 5mL/min, contacts with the solid base catalyst from top to bottom, and the reaction product flows out from the lower end of the trickle bed reactor. The reaction liquid received in the receiving tank is cooled at room temperature, separated by a gas-liquid separator, stirred and crystallized below 10 ℃, filtered and dried to obtain 673g of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide, the content is 99.4%, and the yield is 97%.
Example 2
The N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide is synthesized by adopting a KF/CaO solid base catalyst, and the steps are as follows:
(1) 500g of 4-fluoro-N-isopropylaniline, 110g of sodium carbonate and 400g of water are added into a 2L reaction kettle in sequence and stirred uniformly. 220g of chloroacetyl chloride is added dropwise at the speed of 150g/h under the temperature of 25-30 ℃ to ensure that the temperature can not exceed 30 ℃ all the time. Stirring is continued for 1h after the dripping is completed. Standing for layering, and taking the upper layer as the compound A.
(2) The solid base catalyst is synthesized by an impregnation method: the carrier is KF, the carrier is CaO, and the catalyst preparation steps are the same as those of the example 1, so as to obtain the solid base catalyst KF/CaO.
(3) Compound a was pre-dissolved in 50% ethanol-water solution with a mass ratio of 0.4:1, taking the catalyst as a reaction raw material; 15gKF/CaO solid base catalyst is filled in the constant temperature section of the trickle bed reactor to form a stacked bed layer with the height of 8 cm. The gas pressure of the reaction system is 1MPa, the nitrogen gas is at the linear speed of 0.2m/s, the reaction center temperature is at 100 ℃, the reaction raw material is introduced from the upper end of the trickle bed reactor at the speed of 5mL/min, contacts with the solid base catalyst from top to bottom, and the reaction product flows out from the lower end of the trickle bed reactor. The reaction liquid received in the receiving tank is cooled at room temperature, is separated by a gas-liquid separator, is stirred and crystallized below 10 ℃, is filtered and is dried to obtain 660g of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide, the content is 99.2 percent, and the yield is 95 percent.
Example 3
The method adopts K 2CO3/MgO solid base catalyst to synthesize N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide, and comprises the following steps:
(1) 500g of 4-fluoro-N-isopropylaniline, 110g of sodium carbonate and 400g of water are added into a 2L reaction kettle in sequence and stirred uniformly. 220g of chloroacetyl chloride is added dropwise at the speed of 150g/h under the temperature of 25-30 ℃ to ensure that the temperature can not exceed 30 ℃ all the time. Stirring is continued for 1h after the dripping is completed. Standing for layering, and taking the upper layer as the compound A.
(2) The solid base catalyst is synthesized by an impregnation method: the carrier is K 2CO3, the carrier is MgO, and the catalyst preparation steps are the same as in example 1, so as to obtain the solid base catalyst K 2CO3/MgO.
(3) Compound a was pre-dissolved in 50% methanol-water solution with a mass ratio of 0.45:1, taking the catalyst as a reaction raw material; 14.8g K 2CO3/MgO solid base catalyst is filled in the constant temperature section of the trickle bed reactor to form a stacked bed layer with the height of 8 cm. The gas pressure of the reaction system is 1MPa, the nitrogen gas is at the linear speed of 0.21m/s, the reaction raw material is introduced from the upper end of the trickle bed reactor at the speed of 5mL/min under the condition that the temperature of the reaction center is 80 ℃, the reaction raw material contacts with the solid base catalyst from top to bottom, and the reaction product flows out from the lower end of the trickle bed reactor. The reaction liquid received in the receiving tank is cooled at room temperature, is separated by a gas-liquid separator, is stirred and crystallized below 10 ℃, is filtered and is dried to obtain 640g of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide, the content is 99.1 percent, and the yield is 92 percent.
Comparative example 1
According to US5631403a, the alkaline hydrolysis with sodium carbonate is carried out, and comparative evaluation is carried out, the procedure being as follows:
In a 500mL reaction vessel, 23.0g of 4-fluoro-N-isopropylaniline, 11.7g of sodium carbonate, 140mL of water and 200mL of N-methylpyrrolidone were added, and the mixture was refluxed at 100℃for 2.5 hours. The solvent is distilled off under reduced pressure at 132-135 ℃ to finally obtain 18.1g of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide with the content of 99.1 percent and the yield of 86 percent.
Comparative example 2
According to the teaching of patent US5808152a, N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide was prepared from 2-chloro-N- (4-fluorophenyl) -N- (1-methylethyl) acetamide using aqueous sodium formate for comparative evaluation, the procedure is as follows:
229.68g of 2-chloro-N- (4-fluorophenyl) -N- (1-methylethyl) acetamide and 272 g of 30% aqueous sodium formate were added to the reaction vessel and heated to reflux at 107℃for 1h, slow removal of water from the system was started using a water separator, the reflux temperature of the system was raised to 130℃and maintained for 3h, slow removal of water was continued, and the reflux temperature was raised to 140℃and maintained for 1h. Cooling to 70 ℃, adding toluene solvent, and cooling to room temperature. Adding sodium hydroxide aqueous solution with the same mole as sodium formate to adjust the pH=12-13, neutralizing formic acid generated by ester hydrolysis under high temperature condition and providing alkaline environment to promote the hydrolysis of the residual ester, and stirring for 30min at room temperature. Separating liquid, distilling, desolventizing and recrystallizing to obtain 194.4g of N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide, wherein the content is 96.7 percent and the yield is 89 percent. However, the method generates a large amount of high-salt wastewater, needs recrystallization and has high treatment cost.
The foregoing is merely a preferred embodiment of the present invention, and it should be noted that the above-mentioned preferred embodiment should not be construed as limiting the invention, and the scope of the invention should be defined by the appended claims. It will be apparent to those skilled in the art that various modifications and adaptations can be made without departing from the spirit and scope of the invention, and such modifications and adaptations are intended to be comprehended within the scope of the invention.
Claims (7)
1. A method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide, comprising the steps of:
a: mixing 4-fluoro-N-isopropylaniline, sodium carbonate and water, and dropwise adding chloroacetyl chloride to obtain 2-chloro-N- (4-fluorophenyl) -N-isopropyl acetamide;
B: filling a solid base catalyst into a trickle bed reactor to form a stacked bed; the pressure of the reaction system is 1-1.2MPa, and nitrogen enters a trickle bed reactor; dissolving 2-chloro-N- (4-fluorophenyl) -N-isopropyl acetamide in an alcohol-water mixed solution, introducing the solution from the upper end of a trickle bed reactor, contacting the solution with a solid base catalyst from top to bottom, and flowing out a reaction product from the lower end of the trickle bed reactor; cooling the reaction product, separating by a gas-liquid separator, and crystallizing at low temperature to obtain N- (4-fluoroaniline) -2-hydroxy-N-isopropyl acetamide; the solid base catalyst is KF/MgO, KF/CaO, KF/BaO, K 2CO3/MgO、K2CO3/CaO or K 2CO3/BaO; the alcohol is one or more of methanol, ethanol, n-propanol or isopropanol.
2. The method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide of claim 1, wherein: in the step A, the temperature of dropwise adding chloracetyl chloride is 15-45 ℃.
3. The method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide of claim 1, wherein: in step B, the catalyst filling height is 6-10cm.
4. The method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide of claim 1, wherein: in the step B, the nitrogen linear velocity is 0.1-0.3 m/s.
5. The method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide of claim 1, wherein: in the step B, the reaction temperature is 80-140 ℃.
6. The method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide of claim 1, wherein: in the step B, the mass ratio of the 2-chloro-N- (4-fluorophenyl) -N-isopropyl acetamide to the alcohol-water mixed solution is 0.1-1: 1, a step of; in the alcohol-water mixed solution, the mass ratio of the alcohol to the water is 0.5-1.5: 1.
7. The method for synthesizing N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide of claim 1, wherein: in the step B, the reaction liquid is contacted and reacted with the catalyst reaction center from top to bottom at the flow rate of 4-6 mL/min.
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|---|---|---|---|---|
| US5616799A (en) * | 1994-04-19 | 1997-04-01 | Hoechst Aktiengesellschaft | Process for the preparation of glycoloylanilides |
| US5631403A (en) * | 1994-06-23 | 1997-05-20 | Hoechst Ag | Process for the preparation of hydroxycarboxanilides |
| US5808152A (en) * | 1997-12-12 | 1998-09-15 | Bayer Corporation | Synthesis of N-(4-fluorophenyl)-2-hydroxy-N-(1-methylethyl)acetamide using sodium formate |
| CN107721948A (en) * | 2017-11-16 | 2018-02-23 | 江苏绿叶农化有限公司 | A kind of preparation method of flufenacet |
| CN113461558A (en) * | 2021-06-28 | 2021-10-01 | 宁夏常晟药业有限公司 | Synthesis method of N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide |
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| US5616799A (en) * | 1994-04-19 | 1997-04-01 | Hoechst Aktiengesellschaft | Process for the preparation of glycoloylanilides |
| US5631403A (en) * | 1994-06-23 | 1997-05-20 | Hoechst Ag | Process for the preparation of hydroxycarboxanilides |
| US5808152A (en) * | 1997-12-12 | 1998-09-15 | Bayer Corporation | Synthesis of N-(4-fluorophenyl)-2-hydroxy-N-(1-methylethyl)acetamide using sodium formate |
| CN107721948A (en) * | 2017-11-16 | 2018-02-23 | 江苏绿叶农化有限公司 | A kind of preparation method of flufenacet |
| CN113461558A (en) * | 2021-06-28 | 2021-10-01 | 宁夏常晟药业有限公司 | Synthesis method of N- (4-fluoroaniline) -2-hydroxy-N-isopropylacetamide |
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