CN117777129A - Synthesis method of trifluramide - Google Patents
Synthesis method of trifluramide Download PDFInfo
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- CN117777129A CN117777129A CN202311832400.4A CN202311832400A CN117777129A CN 117777129 A CN117777129 A CN 117777129A CN 202311832400 A CN202311832400 A CN 202311832400A CN 117777129 A CN117777129 A CN 117777129A
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- 238000001308 synthesis method Methods 0.000 title claims description 5
- 238000006243 chemical reaction Methods 0.000 claims abstract description 135
- SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 claims abstract description 102
- 238000007363 ring formation reaction Methods 0.000 claims abstract description 45
- WXNPZQIRDCDLJD-UHFFFAOYSA-N 3-chloro-5-(trifluoromethyl)pyridin-2-amine Chemical compound NC1=NC=C(C(F)(F)F)C=C1Cl WXNPZQIRDCDLJD-UHFFFAOYSA-N 0.000 claims abstract description 44
- 238000000034 method Methods 0.000 claims abstract description 42
- 238000006482 condensation reaction Methods 0.000 claims abstract description 37
- 239000002904 solvent Substances 0.000 claims abstract description 23
- IARIOWWBALBFKZ-UHFFFAOYSA-N 2-chloro-5-methoxybenzenesulfonamide Chemical compound COC1=CC=C(Cl)C(S(N)(=O)=O)=C1 IARIOWWBALBFKZ-UHFFFAOYSA-N 0.000 claims abstract description 19
- 239000003054 catalyst Substances 0.000 claims abstract description 19
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 18
- 239000002253 acid Substances 0.000 claims abstract description 16
- 230000009471 action Effects 0.000 claims abstract description 7
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 51
- 238000005086 pumping Methods 0.000 claims description 44
- 239000012295 chemical reaction liquid Substances 0.000 claims description 42
- 238000003756 stirring Methods 0.000 claims description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 27
- 238000002425 crystallisation Methods 0.000 claims description 23
- 230000008025 crystallization Effects 0.000 claims description 23
- 239000007788 liquid Substances 0.000 claims description 22
- -1 trifluralin amide Chemical class 0.000 claims description 21
- 239000000203 mixture Substances 0.000 claims description 18
- SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 claims description 17
- 239000007864 aqueous solution Substances 0.000 claims description 13
- PRRZDZJYSJLDBS-UHFFFAOYSA-N 3-bromo-2-oxopropanoic acid Chemical compound OC(=O)C(=O)CBr PRRZDZJYSJLDBS-UHFFFAOYSA-N 0.000 claims description 12
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 12
- COTHYYYVPUZALV-UHFFFAOYSA-N hydroxy(trimethyl)silane;potassium Chemical group [K].C[Si](C)(C)O COTHYYYVPUZALV-UHFFFAOYSA-N 0.000 claims description 12
- 238000003786 synthesis reaction Methods 0.000 claims description 12
- 230000015572 biosynthetic process Effects 0.000 claims description 11
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- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 6
- LCTONWCANYUPML-UHFFFAOYSA-N Pyruvic acid Chemical class CC(=O)C(O)=O LCTONWCANYUPML-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
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 239000000126 substance Substances 0.000 claims description 5
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
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- 150000001335 aliphatic alkanes Chemical class 0.000 claims description 2
- 150000002632 lipids Chemical class 0.000 claims description 2
- 239000003208 petroleum Substances 0.000 claims description 2
- LBKJNHPKYFYCLL-UHFFFAOYSA-N potassium;trimethyl(oxido)silane Chemical compound [K+].C[Si](C)(C)[O-] LBKJNHPKYFYCLL-UHFFFAOYSA-N 0.000 claims description 2
- DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 claims description 2
- AAPLIUHOKVUFCC-UHFFFAOYSA-N trimethylsilanol Chemical class C[Si](C)(C)O AAPLIUHOKVUFCC-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- 239000005456 alcohol based solvent Substances 0.000 claims 1
- 239000004210 ether based solvent Substances 0.000 claims 1
- 229940107700 pyruvic acid Drugs 0.000 claims 1
- 239000012535 impurity Substances 0.000 abstract description 11
- 239000000243 solution Substances 0.000 description 32
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- 239000002994 raw material Substances 0.000 description 22
- 238000010992 reflux Methods 0.000 description 20
- 238000005070 sampling Methods 0.000 description 16
- 230000000052 comparative effect Effects 0.000 description 15
- 230000020477 pH reduction Effects 0.000 description 15
- BNADDMQVCIRZBW-UHFFFAOYSA-N 8-chloro-6-(trifluoromethyl)imidazo[1,2-a]pyridine-2-carboxylic acid Chemical compound C1=C(C(F)(F)F)C=C(Cl)C2=NC(C(=O)O)=CN21 BNADDMQVCIRZBW-UHFFFAOYSA-N 0.000 description 12
- 238000009833 condensation Methods 0.000 description 12
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- 238000001816 cooling Methods 0.000 description 9
- 238000010438 heat treatment Methods 0.000 description 7
- 239000013078 crystal Substances 0.000 description 6
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 5
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
- 238000007086 side reaction Methods 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- 238000004458 analytical method Methods 0.000 description 3
- 230000007613 environmental effect Effects 0.000 description 3
- IJPFMKVHJGPXFQ-UHFFFAOYSA-N 1,2,2-trifluoropiperidine Chemical compound FN1CCCCC1(F)F IJPFMKVHJGPXFQ-UHFFFAOYSA-N 0.000 description 2
- 150000001408 amides Chemical class 0.000 description 2
- 230000009286 beneficial effect Effects 0.000 description 2
- 238000006298 dechlorination reaction Methods 0.000 description 2
- ARFLASKVLJTEJD-UHFFFAOYSA-N ethyl 2-bromopropanoate Chemical compound CCOC(=O)C(C)Br ARFLASKVLJTEJD-UHFFFAOYSA-N 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 229910000027 potassium carbonate Inorganic materials 0.000 description 2
- 238000004321 preservation Methods 0.000 description 2
- 238000006798 ring closing metathesis reaction Methods 0.000 description 2
- ABNQGNFVSFKJGI-UHFFFAOYSA-N 2,3-dichloro-5-(trifluoromethyl)pyridine Chemical compound FC(F)(F)C1=CN=C(Cl)C(Cl)=C1 ABNQGNFVSFKJGI-UHFFFAOYSA-N 0.000 description 1
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
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- 235000011114 ammonium hydroxide Nutrition 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 230000007547 defect Effects 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 238000005516 engineering process Methods 0.000 description 1
- 125000004185 ester group Chemical group 0.000 description 1
- 238000010812 external standard method Methods 0.000 description 1
- 230000003301 hydrolyzing effect Effects 0.000 description 1
- 230000006872 improvement Effects 0.000 description 1
- 238000009776 industrial production Methods 0.000 description 1
- 239000007791 liquid phase Substances 0.000 description 1
- 230000007774 longterm Effects 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 239000005645 nematicide Substances 0.000 description 1
- 238000004064 recycling Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 238000007142 ring opening reaction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 150000003456 sulfonamides Chemical class 0.000 description 1
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- Nitrogen Condensed Heterocyclic Rings (AREA)
Abstract
The invention relates to a method for synthesizing triflumidamide, which comprises the following steps: step 1, microwave cyclization reaction: performing microwave cyclization reaction on 2-amino-3-chloro-5-trifluoromethylpyridine and halopyruvic acid in the presence of a solvent A and acid to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid and crystallizing; step 2, microwave condensation reaction: and carrying out microwave condensation reaction on 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-formic acid and 2-chloro-5-methoxybenzene sulfonamide in a solvent B under the action of a catalyst to generate the trifluramide. The method has the advantages of short reaction condition temperature, short time consumption, no generation of dechlorinated impurities, high yield and good purity.
Description
Technical Field
The invention belongs to the technical field of chemical synthesis, and particularly relates to a synthesis method of triflumidamide.
Background
Trifluzaindolizine is a class of sulfonamide nematicides and is widely applied due to the characteristics of wide application range of crops, wide control spectrum, safety to users, environmental friendliness and the like.
In relation to the synthesis of triflumidamide, the methods reported so far are as follows: taking 2, 3-dichloro-5-trifluoromethyl pyridine as a starting material, and carrying out aminolysis under the action of 28% ammonia water; then cyclizing with ethyl bromopropionate, and hydrolyzing to obtain 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid; then under the action of thionyl chloride, 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formyl chloride is generated, and then the product reacts with 2-chloro-5-methoxyl benzenesulfonyl to obtain the target product of the trifluramide. The problems that exist are: the method has the advantages of complicated route steps, long time consumption, low production efficiency, low yield, low purity, large process solvent consumption and low recycling rate, and can generate a large amount of dechlorinated impurities, thereby being not in line with the requirements of safety and environmental protection and being not beneficial to industrial production.
Disclosure of Invention
The invention aims to overcome the defects in the prior art and provides a method for synthesizing the trifluramide, which has the advantages of short reaction condition temperature, short time consumption, no dechlorination impurity generation, high yield and good purity.
In order to achieve the above purpose, the technical scheme adopted by the invention is as follows:
a method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization reaction: performing microwave cyclization reaction on 2-amino-3-chloro-5-trifluoromethylpyridine and halopyruvic acid in the presence of a solvent A and an acidic substance to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid and crystallizing;
step 2, microwave condensation reaction: and carrying out microwave condensation reaction on 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-formic acid and 2-chloro-5-methoxybenzene sulfonamide in a solvent B under the action of a catalyst to generate the trifluramide.
As a further technical scheme, in the step 1, the solvent A is one or more of ethanol, acetonitrile, toluene and xylene;
as a further technical scheme, the halogenated pyruvic acid is selected from one or more of bromopyruvate and iodinated pyruvic acid;
as a further technical scheme, in the step 1, the molar ratio of the 2-amino-3-chloro-5-trifluoromethylpyridine to the halopyruvic acid is 1:1.0-1.15.
As a further technical scheme, in the step 1, the acidic substance adopts one or more of sulfuric acid, hydrochloric acid and acetic acid (preferably acetic acid).
As a further technical scheme, the pumping amount of the acidic substance is 10% of the weight of the 2-amino-3-chloro-5-trifluoromethylpyridine.
As a further technical scheme, in step 1, the microwave cyclization reaction is performed in a microwave reactor, and reaction parameters of the microwave cyclization reaction are as follows: the microwave power is 100-500W, the stirring speed is 150-350r/min, the reaction temperature is 100-150 ℃, and the reaction time is 20-60min.
As a further technical scheme, in step 1, the microwave cyclization reaction and acidification specifically includes: respectively dissolving 2-amino-3-chloro-5-trifluoromethyl pyridine and halopyruvic acid in a solvent A, respectively pumping the solvent A into a microwave reactor at the same time, pumping acetic acid into the microwave reactor, performing microwave cyclization reaction at the microwave reaction power of 100-500W, the reaction temperature of 100-150 ℃ and the stirring speed of 150-350r/min for 20-60min, and after the reaction is finished, generating 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-formic acid and crystallizing to obtain a reaction solution containing 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-formic acid.
As a further technical scheme, in the microwave cyclization reaction, a condensing tube is simultaneously arranged for reflux.
As a further technical scheme, in the step 2, the catalyst adopts trimethylsilyl alkoxide; the trimethylsilanol salt is potassium Trimethylsilanol (TMSOK);
as a further technical scheme, in the step 2, the molar ratio of the 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, the trimethylsilyl alkoxide and the 2-chloro-5-methoxybenzenesulfonamide is 1:1.2-1.4:1.05-1.2.
As a further technical scheme, in step 2, reaction parameters of the microwave condensation reaction are as follows: the microwave power is 200-300w, the stirring speed is 500-1000r/min, the reaction temperature is 80-85 ℃, and the reaction time is 8-15min.
As a further technical scheme, in the step 2, the solvent B includes one or more of a lipid solvent, an ether solvent, an alcohol solvent and an alkane solvent;
as a further technical scheme, the solvent B is one or more selected from ethyl acetate, sec-butyl acetate, diethyl ether, petroleum ether, dichloroethane and dichloromethane.
As a further technical scheme, in step 2, the microwave condensation reaction specifically includes:
mixing 2-chloro-5-methoxybenzene sulfonamide, catalyst and dichloroethane, then respectively pumping the mixture and the reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid into a microwave reactor at the same time, carrying out microwave condensation reaction at the microwave reaction power of 200-300W, the reaction temperature of 80-85 ℃ and the stirring speed of 500-1000r/min for 8-15min, transferring the reaction liquid into a crystallization kettle after the reaction is finished, adjusting the pH value of the reaction liquid to 2 by acid liquor, crystallizing at the temperature of 10-15 ℃, and filtering to obtain the triflumidamide.
As a further technical scheme, in the microwave condensation reaction, a condensing tube is simultaneously configured for reflux.
As a further technical scheme, the acid solution is 5% hydrochloric acid aqueous solution.
The synthetic route of the invention is as follows:
compared with the prior art, the invention has the beneficial effects that:
the invention takes 2-amino-3-chloro-5-trifluoromethylpyridine and halopyruvic acid as raw materials to carry out cyclization reaction, and the 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid can be directly generated after the cyclization reaction, compared with the traditional technology that ethyl bromopropionate and 2-amino-3-chloro-5-trifluoromethylpyridine are adopted to form the ring, the alkaline hydrolysis process of ester groups is omitted, the reaction steps are shortened, and the reaction process is simplified; however, it also brings new technical problems: for example, the ring-closure reaction difficulty of halopyruvic acid and 2-amino-3-chloro-5-trifluoromethyl pyridine is higher, the ring-closure reaction needs to be carried out for more than ten hours at the reaction temperature of 60-80 ℃, and the ring-closure reaction can be carried out simultaneously at the same time, so that the raw material conversion rate is extremely low even if the ring-closure reaction is carried out for a long time, the raw material conversion rate is improved after the temperature is increased, but the reaction time still needs to be more than ten hours, side reactions are easy to occur at long-term high temperature, the impurity content is increased, tar is easy to be generated, and the product yield is further reduced; in order to solve the series of problems caused by taking halogenated pyruvic acid as a raw material, the traditional jacket heating or water bath heating mode is replaced by the microwave heating mode, the reaction time is greatly shortened by improving the reaction temperature, the occurrence of side reaction is reduced, meanwhile, the closed loop can be promoted to be more thorough by adding acid for acidification, the occurrence of the side reaction is further reduced, the production of impurities is reduced, and the reaction yield and the product purity are greatly improved.
The invention adopts 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid and 2-chloro-5-methoxybenzene sulfonamide as raw materials to carry out condensation reaction under the action of a condensation catalyst to synthesize the trifluoro-piperidine amide, compared with the prior art that 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid firstly generates 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formyl chloride under the action of thionyl chloride and then reacts with 2-chloro-5-methoxybenzene sulfonyl to generate the trifluoro-piperidine amide, the invention not only shortens the reaction step, but also avoids the generation of dechlorinated impurities.
In conclusion, the invention develops a new synthesis route of the trifluramide, and compared with the prior art, the synthesis route has the advantages of fewer reaction steps, short reaction time, mild reaction conditions, no dechlorination impurity, great reduction of the danger and environmental protection pressure of the synthesis method of the trifluramide, and great improvement of the yield and purity of the trifluramide.
Detailed Description
The technical solutions of the present invention will be clearly and fully described below with reference to specific embodiments, and it is apparent that the described embodiments are some embodiments of the present invention, but not all embodiments. All other embodiments, which can be made by those skilled in the art based on the embodiments of the invention without making any inventive effort, are intended to be within the scope of the invention.
Example 1
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization and acidification reaction: respectively dissolving 20g of 2-amino-3-chloro-5-trifluoromethylpyridine (content 98%) and 20.8g of bromopyruvate in 200ml of ethanol, then respectively pumping into a microwave reactor at a flow rate of 5ml/s, pumping 2g of acetic acid, performing microwave cyclization reaction at a microwave power of 200W, a stirring rate of 200r/min and a reaction temperature of 110 ℃, configuring a condenser pipe for reflux, starting timing with the end time of pumping 2-amino-3-chloro-5-trifluoromethylpyridine solution into the microwave reactor, reacting for 30min to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, crystallizing to obtain a reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, sampling and controlling the reaction feed liquid to ensure that the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid is 96.23%, and the normalized content of the raw material 2-amino-3-chloro-5-trifluoromethylpyridine is 0.48%; the sampling method of the central control feed liquid is characterized in that when the stirring rotation speed is 120r/min (the precipitated crystals are extremely small in the reaction process, and therefore the crystals can be uniformly dispersed only by stirring at the rotation speed of 120 r/min), a suction pipe is used for stretching into the liquid surface below 1cm to take 0.5ml of the liquid to be in a sampling pipe, 0.25ml of dichloroethane is added, and the liquid phase is fed for analysis after shaking.
Step 2, microwave condensation reaction: mixing 26.0g of 2-chloro-5-methoxybenzene sulfonamide, 17.0g of condensation catalyst trimethylsilanol potassium and 200ml of dichloroethane, then pumping the mixture into a microwave reactor at a flow rate of 5ml/s with the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid obtained in the step 1, carrying out microwave condensation reaction at a microwave power of 250W, a stirring rate of 700r/min and a reaction temperature of 85 ℃, configuring a condensing tube for reflux, starting timing at the end time of pumping the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid into the microwave reactor, ending the reaction for 8min, transferring the reaction liquid into a crystallization kettle, then dropwise adding 5% hydrochloric acid aqueous solution until the pH value of the reaction liquid is 2.0, cooling to 15 ℃ for crystallization, and filtering to obtain 43.06g of a trifluoro imidamide product; the content is 98.06 percent and the total yield is 89.85 percent.
Example 2
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization and acidification reaction: respectively dissolving 20g of 2-amino-3-chloro-5-trifluoromethylpyridine (content 98%) and 20.8g of bromopyruvate in 200ml of ethanol, then respectively pumping into a microwave reactor at the flow rate of 5ml/s, continuously pumping 2g of acetic acid, performing microwave cyclization reaction at the reaction temperature of 110 ℃ and the stirring rate of 300r/min under the microwave power of 200W, configuring a condenser tube for reflux, starting timing with the end time of pumping 2-amino-3-chloro-5-trifluoromethylpyridine solution into the microwave reactor, reacting for 30min to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, crystallizing to obtain a reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, sampling and controlling the reaction feed liquid in a mode, wherein the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid in the reaction feed liquid is normalized to 95.22% and the normalized content of 2-amino-3-chloro-5-trifluoromethylpyridine is 0.70%; the sampling center control method is the same as in example 1;
step 2, microwave condensation reaction: mixing 26.0g of 2-chloro-5-methoxybenzenesulfonamide, 17.0g of condensation catalyst potassium trimethylsilanol and 200ml of dichloroethane, then pumping the mixture into a microwave reactor at a flow rate of 5ml/s with the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid obtained in the step 1, respectively, carrying out microwave condensation reaction at a microwave power of 250W, a stirring rate of 700r/min and a reaction temperature of 85 ℃, configuring a condensing tube for reflux, starting timing at the end time of pumping the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid into the microwave reactor, ending the reaction for 8min, transferring the reaction liquid into a crystallization kettle, then dropwise adding 5% hydrochloric acid aqueous solution until the pH value of the reaction liquid is 2.0, cooling to 15 ℃ for crystallization, and filtering to obtain 44.14g of trifluoro-imidamide product; the content was 97.12% and the total yield was 91.32%.
Example 3
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization and acidification reaction: respectively dissolving 20g of 2-amino-3-chloro-5-trifluoromethylpyridine (content 98%) and 20.8g of bromopyruvate in 200ml of ethanol, pumping 2g of acetic acid into a microwave reactor at the flow rate of 5ml/s, performing microwave cyclization reaction at the reaction temperature of 110 ℃ and the stirring rate of 300r/min under 210W of microwave power, configuring a condensing tube for reflux, starting timing with the end time of pumping 2-amino-3-chloro-5-trifluoromethylpyridine solution into the microwave reactor, reacting for 30min to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, crystallizing to obtain reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, sampling, and controlling the content of the 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid in the reaction feed liquid to be 95.81%, wherein the normalized content of the raw material 2-amino-3-chloro-5-trifluoromethylpyridine is 0.64%; the sampling center control method is the same as in example 1;
step 2, microwave condensation reaction: mixing 26.0g of 2-chloro-5-methoxybenzene sulfonamide, 17.0g of condensation catalyst trimethylsilanol potassium and 200ml of dichloroethane, then pumping the mixture into a microwave reactor at a flow rate of 5ml/s with the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid obtained in the step 1, carrying out microwave condensation reaction at a microwave power of 250W, a stirring rate of 700r/min and a reaction temperature of 85 ℃, configuring a condensing tube for reflux, starting timing at the end time of pumping the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid into the microwave reactor, ending the reaction for 8min, transferring the reaction liquid into a crystallization kettle, then dropwise adding 5% hydrochloric acid aqueous solution until the pH value of the reaction liquid is 2.0, cooling to 15 ℃ for crystallization, and filtering to obtain 43.39g of a trifluoro imidamide product; 97.43% by weight and 90.06% by weight.
Example 4
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization and acidification reaction: respectively dissolving 20g of 2-amino-3-chloro-5-trifluoromethylpyridine (content 98%) and 20.8g of bromopyruvate in 200ml of ethanol, pumping 2g of acetic acid into a microwave reactor at the flow rate of 5ml/s, performing microwave cyclization reaction at the reaction temperature of 110 ℃ and the stirring rate of 220W, configuring a condensing tube for reflux, starting timing with the end time of pumping 2-amino-3-chloro-5-trifluoromethylpyridine solution into the microwave reactor, reacting for 30min to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, crystallizing to obtain a reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, sampling and controlling the reaction feed liquid, wherein the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid in the reaction feed liquid is 95.92%, and the normalized content of 2-amino-3-chloro-5-trifluoromethylpyridine is 0.56%; the sampling center control method is the same as in example 1;
step 2, microwave condensation reaction: mixing 26.0g of 2-chloro-5-methoxybenzene sulfonamide, 17.0g of condensation catalyst trimethylsilanol potassium and 200ml of dichloroethane, pumping the mixture and the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid obtained in the step 1 into a microwave reactor at the flow rate of 5ml/s respectively, performing microwave condensation reaction at the microwave power of 230W, the stirring rate of 800r/min and the reaction temperature of 85 ℃, configuring a condensing tube for reflux, starting timing at the end time of pumping the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid into the microwave reactor, ending the reaction for 8min, transferring the reaction liquid to a crystallization kettle, then dropwise adding 5% hydrochloric acid aqueous solution until the pH value of the reaction liquid is 2.0, cooling to the temperature of 15 ℃ for crystallization, and filtering to obtain 42.54g of trifluoro imidamide product; 98.12% by weight and 88.92% by weight.
Example 5
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization and acidification reaction: respectively dissolving 20g of 2-amino-3-chloro-5-trifluoromethylpyridine (content 98%) and 20.8g of bromopyruvate in 200ml of ethanol, pumping 2g of acetic acid into a microwave reactor at the flow rate of 5ml/s, performing microwave cyclization reaction at the reaction temperature of 110 ℃ and the stirring rate of 300r/min under the microwave power of 220W, configuring a condensing tube for reflux, starting timing with the end time of pumping 2-amino-3-chloro-5-trifluoromethylpyridine solution into the microwave reactor, reacting for 30min to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, and crystallizing to obtain reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid; sampling and controlling, wherein the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid in the reaction liquid is 95.27%, and the normalized content of the raw material 2-amino-3-chloro-5-trifluoromethyl pyridine is 0.72%; the sampling center control method is the same as in example 1;
step 2, microwave condensation reaction: mixing 23.9g of 2-chloro-5-methoxybenzene sulfonamide, 16.5g of condensation catalyst potassium trimethylsilanol and 200ml of dichloroethane, pumping the mixture and the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid obtained in the step 1 into a microwave reactor at the flow rate of 5ml/s respectively, performing microwave condensation reaction at the microwave power of 230W, the stirring rate of 800r/min and the reaction temperature of 82 ℃, configuring a condensing tube for reflux, starting timing at the end time of pumping the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid into the microwave reactor, ending the reaction for 8min, transferring the reaction liquid to a crystallization kettle, then dropwise adding 5% hydrochloric acid aqueous solution until the pH value of the reaction liquid is 2.0, cooling to the temperature of 15 ℃ for crystallization, and filtering to obtain 40.42g of a trifluoro imidamide product; the content was 97.94% and the total yield was 88.53%.
Example 6
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization and acidification reaction: respectively dissolving 20g of 2-amino-3-chloro-5-trifluoromethylpyridine (content 98%) and 20.8g of bromopyruvate in 200ml of ethanol, pumping 2g of acetic acid into a microwave reactor at the flow rate of 5ml/s, performing microwave cyclization reaction at the reaction temperature of 110 ℃ and the stirring rate of 220W, configuring a condensing tube for reflux, starting timing with the end time of pumping 2-amino-3-chloro-5-trifluoromethylpyridine solution into the microwave reactor, reacting for 30min to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, crystallizing to obtain reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, sampling, and controlling the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid in the reaction feed liquid to 95.18%, wherein the normalized content of the raw material 2-amino-3-chloro-5-trifluoromethylpyridine is 0.66%; the sampling center control method is the same as in example 1;
step 2, microwave condensation reaction: mixing 24.0g of 2-chloro-5-methoxybenzene sulfonamide, 16.0g of condensation catalyst potassium trimethylsilanol and 200ml of dichloroethane, pumping the mixture and the reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid obtained in the step 1 into a microwave reactor at the flow rate of 5ml/s respectively, performing microwave condensation reaction at the microwave power of 250W, the stirring rate of 800r/min and the reaction temperature of 80 ℃, configuring a condensing tube for reflux, starting timing at the end time of pumping the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid into the microwave reactor, ending the reaction for 8min, transferring the reaction liquid to a crystallization kettle, then dropwise adding 5% hydrochloric acid aqueous solution until the pH value of the reaction liquid is 2.0, cooling to the temperature of 15 ℃ for crystallization, and filtering to obtain 42.90g of a trifluoro imidamide product; the content was 97.68% and the total yield was 89.26%.
Example 7
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization and acidification reaction: respectively dissolving 20g of 2-amino-3-chloro-5-trifluoromethylpyridine (content 98%) and 20.8g of bromopyruvate in 200ml of ethanol, pumping 2g of acetic acid into a microwave reactor at the flow rate of 5ml/s, performing microwave cyclization reaction at the reaction temperature of 110 ℃ and the stirring rate of 300r/min under the microwave power of 230W, configuring a condensing tube for reflux, starting timing with the end time of pumping 2-amino-3-chloro-5-trifluoromethylpyridine solution into the microwave reactor, reacting for 30min to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, and crystallizing to obtain reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid; sampling and controlling, wherein the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid in the reaction liquid is 96.46 percent, and the normalized content of the raw material 2-amino-3-chloro-5-trifluoromethyl pyridine is 0.48 percent; the sampling center control method is the same as in example 1;
step 2, microwave condensation reaction: mixing 24.0g of 2-chloro-5-methoxybenzenesulfonamide, 16.0g of condensation catalyst potassium trimethylsilanol and 200ml of dichloroethane, pumping the mixture and the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid obtained in the step 1 into a microwave reactor at the flow rate of 5ml/s respectively, performing microwave condensation reaction at the microwave power of 250W, the stirring rate of 800r/min and the reaction temperature of 82 ℃, configuring a condensing tube for reflux, starting timing at the end time of pumping the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid into the microwave reactor, ending the reaction for 8min, transferring the reaction liquid to a crystallization kettle, then dropwise adding 5% hydrochloric acid aqueous solution until the pH value of the reaction liquid is 2.0, cooling to the temperature of 15 ℃ for crystallization, and filtering to obtain 43.75g of trifluoro-imidamide product; the content is 97.36 percent and the total yield is 90.75 percent.
Example 8
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization and acidification reaction: respectively dissolving 20g of 2-amino-3-chloro-5-trifluoromethylpyridine (content 98%) and 20.8g of bromopyruvate in 200mL of ethanol, pumping 2g of acetic acid into a microwave reactor at the flow rate of 5mL/s, performing microwave cyclization reaction at the reaction temperature of 110 ℃ and the stirring rate of 200W, configuring a condensing tube for reflux, starting timing with the end time of pumping 2-amino-3-chloro-5-trifluoromethylpyridine solution into the microwave reactor, reacting for 30min to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid, crystallizing, and adding 100mL of dichloroethane to dissolve crystals to obtain a reaction solution containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid; then sampling and controlling, wherein the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid in the reaction liquid is 95.95%, and the normalized content of the raw material 2-amino-3-chloro-5-trifluoromethyl pyridine is 0.58%; meanwhile, the content of the target product 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid in the reaction liquid is measured by adopting an external standard method, and the reaction yield of the step is calculated to be 96.59%;
step 2, microwave condensation reaction: mixing 24.0g of 2-chloro-5-methoxybenzene sulfonamide, 16.0g of condensation catalyst potassium trimethylsilanol and 100ml of dichloroethane, pumping the mixture and the reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-formic acid obtained in the step 1 into a microwave reactor at the flow rate of 5ml/s respectively, performing microwave condensation reaction at the microwave power of 250W, the stirring rate of 700r/min and the reaction temperature of 85 ℃, configuring a condensing tube for reflux, starting timing at the end time of pumping the reaction liquid containing 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-formic acid into the microwave reactor, ending the reaction for 8min, transferring the reaction liquid to a crystallization kettle, then dropwise adding 5% hydrochloric acid aqueous solution until the pH value of the reaction liquid is 2.0, cooling to the temperature of 15 ℃ for crystallization, and filtering to obtain 43.26g of trifluoro imidamide product; the content is 96.71%, and the total yield is 89.11%.
Comparative example 1
A method for synthesizing trifluralin amide comprises the following steps:
step 1, cyclization and acidification reaction: dissolving 20g of 2-amino-3-chloro-5-trifluoromethylpyridine (content 98%) and 20.8g of bromopyruvic acid in 200ml of ethanol respectively, adding 2g of acetic acid, then adding into a three-neck flask, heating to 70 ℃ by adopting a water bath, carrying out heat preservation reaction for 15h at a stirring rate of 300r/min, configuring a condensing tube for reflux to generate 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid, and obtaining a reaction solution containing 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid without crystallization; sampling and control, sampling and control method is the same as in example 1, wherein the normalized content of 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid in the reaction solution is 32.91%, and the normalized content of 2-amino-3-chloro-5-trifluoromethylpyridine is 64.35%.
The subsequent reaction did not proceed.
Comparative example 2
A method for synthesizing trifluralin amide comprises the following steps:
step 1, cyclization and acidification reaction: 20g of 2-amino-3-chloro-5-trifluoromethylpyridine (content 98%) and 20.8g of bromopyruvic acid are respectively dissolved in 200ml of ethanol, 2g of acetic acid is added, then the mixture is added into a three-neck flask, the temperature is raised to 110 ℃ by adopting an oil bath, the mixture is subjected to heat preservation reaction for 15 hours at the stirring rate of 300r/min, a condensing tube is arranged for reflux, and 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid is generated, and crystallization is not carried out, so that a reaction solution containing 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid is obtained; sampling center control, sampling center control method is the same as in example 1; the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid in the reaction solution is 50.06 percent, and the normalized content of 2-amino-3-chloro-5-trifluoromethyl pyridine is 31.23 percent;
the subsequent reaction did not proceed.
Comparative examples 1-2 compare to example 8:
in comparative example 1, water bath heating is adopted and the reaction is carried out at 70 ℃, after the reaction lasts for 15 hours, the yield of the target product is 32.91%, the raw material residue is up to 64.35%, although impurities are few, the raw material conversion efficiency is extremely low, which is probably caused by ring-opening reaction occurring at the same time of ring-closing reaction, the raw material conversion rate is extremely low, after the temperature is increased to 110 ℃, the raw material conversion rate is obviously improved under the same reaction time of 15 hours in comparative example 2, the target product is improved, but some side reactions are increased due to long-time high-temperature reaction, so that impurities are increased, tar is possibly generated, and therefore, the reduced raw material cannot be equal to the increased target product, and in example 8, after the traditional water bath or oil bath heating is improved to microwave heating, the reaction time is shortened to 30 minutes from 15 hours, the reaction rate of ring-closing reaction is greatly improved, tar and other byproducts are avoided, the content of impurities is greatly reduced, and the yield of the target product is greatly improved.
Comparative example 3
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization reaction: the same as in example 8, except that acetic acid was not pumped in; after 30min of reaction, 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid is generated, a small amount of crystals are separated out, sampling is performed, and the sampling and the control method is the same as that of example 1; the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid in the reaction solution is 70.31 percent, and the normalized content of the raw material 2-amino-3-chloro-5-trifluoromethyl pyridine is 10.56 percent.
Comparative example 4
The same as in example 8 except that 1g of acetic acid was pumped and reacted for 30 minutes to produce 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid, a small amount of crystals were precipitated, and the sampling and control method was the same as in example 1; the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid in the reaction solution is 78.64 percent, and the normalized content of the raw material 2-amino-3-chloro-5-trifluoromethyl pyridine is 6.53 percent.
Comparative examples 3-4 compare with example 8:
since the impurity generation is not caused by incomplete ring closure and the ring closure product is opened again under the condition of insufficient consumption of the acetic acid, and the yield of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid is reduced, the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid in the comparative example 3-4 is drastically reduced from 95.92% of the example 8 to 73.31% and 78.64% compared with the example 8.
Comparative example 5
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization and acidification reaction: same as in example 8; performing central control detection on the reaction liquid, wherein the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid in the reaction liquid is 96.12%, and the normalized content of 2-amino-3-chloro-5-trifluoromethyl pyridine is 0.4%;
step 2, microwave condensation reaction: mixing 23.9g of 2-chloro-5-methoxybenzene sulfonamide, 11.7g of condensation catalyst potassium carbonate and 100ml of dichloroethane, pumping the mixture and the reaction solution containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid obtained in the step 1 into a microwave reactor at the flow rate of 5ml/s respectively, performing microwave condensation reaction at the microwave power of 250W, the stirring rate of 700r/min and the reaction temperature of 85 ℃, starting to count the time at the end of pumping the reaction solution containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid into the microwave reactor for 8min, ending the reaction, transferring the reaction solution to a crystallization kettle, then dripping 5% hydrochloric acid aqueous solution until the pH value of the reaction solution is 2.0, cooling to 15 ℃, performing sampling analysis on the reaction solution, wherein the content of the raw material 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-formic acid is 55.44%, and the content of the product is normalized to be normalized to 9%. The reaction is continued for 35 minutes until the normalized content of the raw material 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid is 0.42 percent and the normalized content of the product trifluramide is 94.23 percent.
In this comparative example, the conversion efficiency of raw material 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-carboxylic acid was greatly reduced compared with example 8 by replacing potassium trimethylsilanol of example 8 with potassium carbonate.
Comparative example 6
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization and acidification reaction: same as in example 8; detecting the reaction liquid, wherein the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid in the reaction liquid is 96.44%, and the normalized content of 2-amino-3-chloro-5-trifluoromethyl pyridine is 0.6%;
step 2, microwave condensation reaction: after 25.0g of 2-chloro-5-methoxybenzenesulfonamide and 100ml of dichloroethane are mixed, the mixture is pumped into a microwave reactor at a flow rate of 5ml/s with the reaction solution containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid obtained in the step 1, microwave condensation reaction is carried out at a microwave power of 250W, a stirring rate of 700r/min and a reaction temperature of 85 ℃, the reaction is started by the end time of pumping the reaction solution containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid into the microwave reactor, the reaction is started for 8min, the reaction is ended, the reaction solution is transferred to a crystallization kettle, then 5% hydrochloric acid aqueous solution is dripped until the pH value of the reaction solution is 2.0, then the temperature is reduced to 15 ℃, no crystals are separated out, the sample analysis of the reaction solution is carried out, the normalized content of raw material 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-carboxylic acid is 92.37%, and the normalized content of the product of the triflumidine amide is 0.24%.
In this comparative example, compared with example 8, less triflumidine amide was produced without the use of a condensation catalyst.
Comparative example 7
A method for synthesizing trifluralin amide comprises the following steps:
step 1, microwave cyclization and acidification reaction: as in example 1; detecting a reaction solution, wherein the normalized content of 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid in the reaction solution is 96.57%, and the normalized content of 2-amino-3-chloro-5-trifluoromethyl pyridine is 0.5%;
step 2, condensation reaction: 25g of 2-chloro-5-methoxybenzene sulfonamide, 17g of condensation catalyst potassium trimethylsilanol and 200ml of dichloroethane are mixed, then the mixture and the reaction solution containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid obtained in the step 1 are added into a reaction flask at the same time, the mixture is reacted for 10 hours in a water bath at 85 ℃ and at a stirring speed of 700r/min, after the reaction is finished, 5% hydrochloric acid aqueous solution is dropwise added until the pH value of the reaction solution is 2.0, then the mixture is cooled to 15 ℃ for crystallization, and the mixture is filtered, thus 42.98g of trifluramide product is obtained; 96.78% of the total yield 88.61%.
In this comparative example, compared with example 1, the microwave temperature-controlled condensation reaction of example 1 was replaced with a conventional water-bath temperature-controlled condensation reaction, and the reaction was slow and the reaction efficiency was low.
The above described embodiments are only preferred examples of the invention and are not exhaustive of the possible implementations of the invention. Any obvious modifications thereof, which would be apparent to those skilled in the art without departing from the principles and spirit of the present invention, should be considered to be included within the scope of the appended claims.
Claims (10)
1. The synthesis method of the trifluralin amide is characterized by comprising the following steps of:
step 1, microwave cyclization reaction: performing microwave cyclization reaction on 2-amino-3-chloro-5-trifluoromethylpyridine and halopyruvic acid in the presence of a solvent A and an acidic substance to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid and crystallizing;
step 2, microwave condensation reaction: and carrying out microwave condensation reaction on 8-chloro-6- (trifluoromethyl) -imidazo [1,2a ] pyridine-2-formic acid and 2-chloro-5-methoxybenzene sulfonamide in a solvent B under the action of a catalyst to generate the trifluramide.
2. A process for the synthesis of trifluramide according to claim 1, characterized in that,
in the step 1, the solvent A is one or more of ethanol, acetonitrile, toluene and xylene;
the halogenated pyruvic acid is selected from one or more of bromopyruvic acid and iodized pyruvic acid;
in the step 1, the molar ratio of the 2-amino-3-chloro-5-trifluoromethyl pyridine to the halopyruvic acid is 1:1.0-1.15.
3. A process for the synthesis of trifluramide according to claim 1, characterized in that,
in the step 1, the acidic substance is selected from one or more of sulfuric acid, hydrochloric acid and acetic acid.
4. A process for the synthesis of trifluramide according to claim 1, characterized in that,
in the step 1, the microwave cyclization reaction is carried out in a microwave reactor, and the reaction parameters of the microwave cyclization reaction are as follows: the microwave power is 100-500W, the stirring speed is 150-350r/min, the reaction temperature is 100-150 ℃, and the reaction time is 20-60min.
5. A process for the synthesis of trifluramide according to claim 1, characterized in that,
in step 1, the microwave cyclization reaction specifically includes: respectively dissolving 2-amino-3-chloro-5-trifluoromethyl pyridine and halopyruvic acid in a solvent A, respectively pumping the solvent A into a microwave reactor at the same time, pumping acid, and performing microwave cyclization reaction at a microwave reaction power of 100-500W, a reaction temperature of 100-150 ℃ and a stirring speed of 150-350r/min for 20-60min to generate 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid, and crystallizing to obtain a reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid.
6. A process for the synthesis of trifluramide according to claim 1, characterized in that,
in the step 2, the catalyst adopts trimethylsilyl alkoxide; the trimethylsilanol salt is potassium Trimethylsilanol (TMSOK);
in the step 2, the molar ratio of the 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid, the trimethylsilyl alkoxide and the 2-chloro-5-methoxybenzene sulfonamide is 1:1.2-1.4:1.05-1.2.
7. A process for the synthesis of trifluramide according to claim 1, characterized in that,
in the step 2, the reaction parameters of the microwave condensation reaction are as follows: the microwave power is 200-300w, the stirring speed is 500-1000r/min, the reaction temperature is 80-85 ℃, and the reaction time is 8-15min.
8. A process for the synthesis of trifluramide according to claim 1, characterized in that,
in the step 2, the solvent B comprises one or more of lipid solvents, ether solvents, alcohol solvents and alkane solvents;
the solvent B is one or more selected from ethyl acetate, sec-butyl acetate, diethyl ether, petroleum ether, dichloroethane and dichloromethane.
9. A process for the synthesis of trifluramide according to claim 1, characterized in that,
in step 2, the microwave condensation reaction specifically includes:
mixing 2-chloro-5-methoxybenzene sulfonamide, catalyst and dichloroethane, then respectively pumping the mixture and the reaction feed liquid containing 8-chloro-6- (trifluoromethyl) -imidazole [1,2a ] pyridine-2-formic acid into a microwave reactor at the same time, carrying out microwave condensation reaction at the microwave reaction power of 200-300W, the reaction temperature of 80-85 ℃ and the stirring speed of 500-1000r/min for 8-15min, transferring the reaction liquid into a crystallization kettle after the reaction is finished, adjusting the pH value of the reaction liquid to 2 by acid liquor, crystallizing at the temperature of 10-15 ℃, and filtering to obtain the triflumidamide.
10. The method for synthesizing the trifluramide according to claim 9, wherein,
the acid liquor is 5% hydrochloric acid aqueous solution.
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