CN113620830B - Synthesis method of oxadiazon intermediate - Google Patents
Synthesis method of oxadiazon intermediate Download PDFInfo
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- CN113620830B CN113620830B CN202111128981.4A CN202111128981A CN113620830B CN 113620830 B CN113620830 B CN 113620830B CN 202111128981 A CN202111128981 A CN 202111128981A CN 113620830 B CN113620830 B CN 113620830B
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Abstract
The invention belongs to the field of organic synthesis, and particularly relates to a method for synthesizing an oxazachlor intermediate. The method comprises the following steps: a) In the presence of a catalyst, carrying out chlorination reaction on 2- (4-hydroxyphenoxy) propionic acid and a chlorinating agent in an organic solvent to obtain 2- (4-hydroxyphenoxy) propionyl chloride; b) In the presence of an acid binding agent, the 2- (4-hydroxy phenoxy) propionyl chloride and N-methyl-2-fluoroaniline are subjected to condensation reaction in an organic solvent to obtain N- (2-fluorophenyl) -2- (4-hydroxy phenoxy) -N-methylpropanamide. The synthesis method provided by the invention has the advantages of high reaction yield, high product purity, relatively low price and easy obtainment of raw materials, and is suitable for industrial production. The experimental results show that: the reaction yield of the synthesis method provided by the invention is more than 90%, and the product purity is more than 95%.
Description
Technical Field
The invention belongs to the field of organic synthesis, and particularly relates to a synthesis method of an oxazoxamide intermediate N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropanamide.
Background
The oxazoxamide is an aryloxy-phenoxy-propionate herbicide, and is different from other aryloxy-phenoxy-propionate herbicides in that the oxazoxamide has safety to rice, can effectively prevent and remove major weeds such as barnyard grass, moleplant, crabgrass and goosegrass in a paddy field, and is mainly used for transplanting and direct seeding paddy field weeding. The oxazoxamide also has the characteristics of low toxicity, wide miscibility, environmental safety and the like, is hopeful to be used for weeding other crops and lawns, and is a herbicide with development potential. N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropanamide (HPFMPA) is an intermediate of metamifop and is also one of the metabolites of metamifop.
In the method for synthesizing the oxazoxamide disclosed in the document 'novel paddy field herbicide Metamifop', N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropionamide is an important intermediate of the oxazoxamide. The synthesis method comprises the following steps: n- (2-fluorophenyl) -N-methyl-2-bromopropionamide and p-diphenol are used as raw materials, in the presence of potassium carbonate, nucleophilic reaction is carried out to prepare an intermediate (I) N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropionamide, and then the intermediate is reacted with 2, 6-dichlorobenzoxazole (II) to synthesize oxazoxamide (III). However, the first step of the synthesis method is to prepare N- (2-fluorophenyl) -N-methyl-2-bromopropionamide from photoactive 2-bromo-propionic acid and N-methyl-2-fluoroaniline, and the cost is high and the yield is low, so that the synthesis method is not suitable for industrial production.
Disclosure of Invention
In view of the above, the invention aims to provide a synthesis method of an oxazoxamide intermediate N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropanamide, which has high reaction yield and high product purity and is suitable for industrial production.
The invention provides a method for synthesizing an oxazachlor intermediate, which comprises the following steps:
a) In the presence of a catalyst, carrying out chlorination reaction on 2- (4-hydroxyphenoxy) propionic acid and a chlorinating agent in an organic solvent to obtain 2- (4-hydroxyphenoxy) propionyl chloride;
b) In the presence of an acid binding agent, the 2- (4-hydroxy phenoxy) propionyl chloride and N-methyl-2-fluoroaniline are subjected to condensation reaction in an organic solvent to obtain N- (2-fluorophenyl) -2- (4-hydroxy phenoxy) -N-methylpropanamide.
Preferably, in the step a), the chlorinating agent is one or more of thionyl chloride, phosphorus trichloride, phosphorus oxychloride, oxalyl chloride and hypochlorous acid;
the molar ratio of the chlorinating reagent to the 2- (4-hydroxy phenoxy) propionic acid is (0.8-2): 1.
preferably, in step a), the catalyst is one or more of N, N-dimethylformamide, dimethyl sulfoxide, dimethylacetamide and 4-dimethylaminopyridine;
the molar ratio of the catalyst to the 2- (4-hydroxy phenoxy) propionic acid is (0.02-0.1): 1.
preferably, in the step a), the temperature of the chlorination reaction is 30-reflux temperature; the chlorination reaction time is 3-9 h.
Preferably, step a) specifically comprises:
a1 2- (4-hydroxy phenoxy) propionic acid and a catalyst are dissolved in an organic solvent to obtain a mixed solution;
a2 Dropwise adding a chlorinating reagent into the mixed solution under the condition of heating and stirring, and heating the mixed solution to reflux after the dropwise adding is finished;
a3 After the reflux reaction is finished, removing the organic solvent to obtain the 2- (4-hydroxyphenoxy) propionyl chloride.
Preferably, the molar ratio of the N-methyl-2-fluoroaniline to the 2- (4-hydroxyphenoxy) propionic acid is (0.8-2): 1.
preferably, in the step b), the acid binding agent is one or more of sodium hydroxide, potassium carbonate, sodium bicarbonate, triethylamine and sodium methoxide;
the mol ratio of the acid binding agent to the N-methyl-2-fluoroaniline is (1-10): 1.
preferably, in the step b), the temperature of the condensation reaction is-5-10 ℃; the time of the condensation reaction is 3-8 h.
Preferably, step b) specifically comprises:
b1 Dissolving the 2- (4-hydroxyphenoxy) propionyl chloride in an organic solvent to obtain an acyl chloride solution; dissolving N-methyl-2-fluoroaniline and an acid binding agent in an organic solvent to obtain a mixed solution;
b2 Dropwise adding the acyl chloride solution into the mixed solution under the condition of cooling and stirring, and carrying out heat preservation reaction after the dropwise adding is finished;
b3 After the heat preservation reaction is finished, the reaction product is subjected to post-treatment to obtain the N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropanamide.
Preferably, in step b 3), the step of post-processing specifically includes:
b 3-1) sequentially washing, drying, filtering and desolventizing the reaction product to obtain a crude product;
b 3-2) dissolving the crude product in ethanol, then dripping the obtained ethanol solution into petroleum ether, filtering after dripping, and drying to obtain the N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropanamide refined product.
Compared with the prior art, the invention provides a method for synthesizing the oxazachlor intermediate. The synthesis method provided by the invention comprises the following steps: a) In the presence of a catalyst, carrying out chlorination reaction on 2- (4-hydroxyphenoxy) propionic acid and a chlorinating agent in an organic solvent to obtain 2- (4-hydroxyphenoxy) propionyl chloride; b) In the presence of an acid binding agent, the 2- (4-hydroxy phenoxy) propionyl chloride and N-methyl-2-fluoroaniline are subjected to condensation reaction in an organic solvent to obtain N- (2-fluorophenyl) -2- (4-hydroxy phenoxy) -N-methylpropanamide. The synthesis method provided by the invention uses 2- (4-hydroxy phenoxy) propionic acid as an initial raw material, and the initial raw material is subjected to chlorination reaction with a chlorinating agent under the action of a catalyst in an organic solvent system, and then is subjected to condensation reaction with N-methyl-2-fluoroaniline under the action of an acid binding agent, and the target product N- (2-fluorophenyl) -2- (4-hydroxy phenoxy) -N-methylpropanamide is obtained after post treatment. The synthesis method provided by the invention has the advantages of high reaction yield, high product purity, relatively low price and easy obtainment of raw materials, and is suitable for industrial production. The experimental results show that: the reaction yield of the synthesis method provided by the invention is more than 90%, and the product purity is more than 95%.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings that are required to be used in the embodiments or the description of the prior art will be briefly described below, and it is obvious that the drawings in the following description are only embodiments of the present invention, and that other drawings can be obtained according to the provided drawings without inventive effort for a person skilled in the art.
FIG. 1 is a chromatogram provided in example 1 of the present invention;
FIG. 2 is a chromatogram provided in example 2 of the present invention.
Detailed Description
The following description of the embodiments of the present invention will be made clearly and completely, and it is apparent that the described embodiments are only 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.
The invention provides a synthetic method of an oxazoxamide intermediate N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropanamide, which comprises the following steps:
a) In the presence of a catalyst, carrying out chlorination reaction on 2- (4-hydroxyphenoxy) propionic acid and a chlorinating agent in an organic solvent to obtain 2- (4-hydroxyphenoxy) propionyl chloride;
b) In the presence of an acid binding agent, the 2- (4-hydroxy phenoxy) propionyl chloride and N-methyl-2-fluoroaniline are subjected to condensation reaction in an organic solvent to obtain N- (2-fluorophenyl) -2- (4-hydroxy phenoxy) -N-methylpropanamide.
In the synthesis method provided by the invention, in the step a), the catalyst is preferably one or more of N, N-dimethylformamide, dimethyl sulfoxide, dimethylacetamide and 4-dimethylaminopyridine; the molar ratio of the catalyst to 2- (4-hydroxyphenoxy) propionic acid is preferably (0.02-0.1): 1, which may be specifically 0.02:1, 0.03:1, 0.04:1, 0.05:1, 0.06:1, 0.07:1, 0.08:1, 0.09:1, or 0.1:1.
In the synthesis method provided by the invention, in the step a), the chlorinating reagent is preferably one or more of thionyl chloride, phosphorus trichloride, phosphorus oxychloride, oxalyl chloride and hypochlorous acid, and more preferably is thionyl chloride and/or oxalyl chloride; the molar ratio of the chlorinating reagent to 2- (4-hydroxyphenoxy) propionic acid is preferably (0.8-2): 1, which may specifically be 0.8:1, 0.9:1, 1:1, 1.1:1, 1.2:1, 1.3:1, 1.4:1, 1.5:1, 1.6:1, 1.7:1, 1.8:1, 1.9:1 or 2:1.
In the synthesis method provided by the present invention, in step a), the organic solvent is preferably one or more of toluene, xylene, dichloroethane, dichloromethane and cyclohexane, more preferably toluene and/or dichloroethane; the mass ratio of the organic solvent to the 2- (4-hydroxyphenoxy) propionic acid is preferably (10-30): 1, in particular 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1, 20:1, 21:1, 22:1, 23:1, 24:1, 25:1, 26:1, 27:1, 28:1, 29:1 or 30:1.
In the synthesis method provided by the invention, in the step a), the temperature of the chlorination reaction is preferably 30-reflux temperature, more preferably 45-reflux temperature; the time of the chlorination reaction is preferably 3 to 9 hours, and may specifically be 3 hours, 3.5 hours, 4 hours, 4.5, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 7.5 hours, 8 hours, 8.5 hours or 9 hours.
In the synthesis method provided by the invention, the step a) preferably specifically comprises the following steps:
a1 2- (4-hydroxy phenoxy) propionic acid and a catalyst are dissolved in an organic solvent to obtain a mixed solution;
a2 Dropwise adding a chlorinating reagent into the mixed solution under the condition of heating and stirring, and heating the mixed solution to reflux after the dropwise adding is finished;
a3 After the reflux reaction is finished, removing the organic solvent to obtain the 2- (4-hydroxyphenoxy) propionyl chloride.
In the synthesis method provided by the present invention, in step a 2), the dropping temperature is preferably 30 to 70 ℃, more preferably 45 to 70 ℃, and particularly 30 ℃, 35 ℃, 40 ℃, 45 ℃,50 ℃,55 ℃, 60 ℃, 65 ℃ or 70 ℃; the total time of the dropping and refluxing reaction is preferably 3 to 9 hours, and may specifically be 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 7.5 hours, 8 hours, 8.5 hours or 9 hours, wherein the time of the dropping is preferably 1 to 2 hours, and may specifically be 1 hour, 1.5 hours or 2 hours, and the time of the refluxing reaction is preferably 2 to 6 hours, and may specifically be 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours or 6 hours.
In the synthesis method provided by the invention, in the step a 3), the mode of removing the organic solvent is preferably negative pressure distillation; the vacuum degree of the negative pressure distillation is preferably 0.08-0.095 MPa; the temperature of the negative pressure distillation is preferably 40 to 60 ℃, and may be particularly 50 ℃.
In the synthesis method provided by the invention, oxalyl chloride is selected as an example of a chlorinating reagent, and the chlorination reaction process involved in the step a) is as follows:
in the synthesis method provided by the invention, in the step b), the acid-binding agent is an inorganic base and/or an organic base, preferably one or more of sodium hydroxide, potassium carbonate, sodium bicarbonate, triethylamine and sodium methoxide, more preferably sodium bicarbonate and/or triethylamine; the molar ratio of the acid binding agent to the N-methyl-2-fluoroaniline is preferably (1-10): 1, more preferably (2 to 7): 1, may specifically be 1:1, 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1 or 10:1.
In the synthesis method provided by the invention, in the step b), the molar ratio of the 2- (4-hydroxyphenoxy) propionyl chloride to the N-methyl-2-fluoroaniline, calculated on the basis of the amount of the raw material 2- (4-hydroxyphenoxy) propionic acid, is preferably 1: (0.8-2), which may be specifically 1:0.8, 1:0.9, 1:1, 1:1.1, 1:1.2, 1:1.3, 1:1.4, 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9 or 1:2.
In the synthesis method provided by the present invention, in step b), the organic solvent is preferably one or more of toluene, xylene, dichloroethane, dichloromethane and cyclohexane, more preferably toluene and/or dichloroethane; the mass ratio of the organic solvent to the N-methyl-2-fluoroaniline is preferably (2-20): 1, more preferably (4 to 10): 1, in particular 2:1, 3:1, 4:1, 5:1, 6:1, 7:1, 8:1, 9:1, 10:1, 11:1, 12:1, 13:1, 14:1, 15:1, 16:1, 17:1, 18:1, 19:1 or 20:1.
In the synthesis method provided by the present invention, in step b), the temperature of the condensation reaction is preferably-5 to 10 ℃, more preferably 0 to 10 ℃, and specifically can be-5 ℃, -4 ℃, -3 ℃, -2 ℃, -1 ℃, 0 ℃,1 ℃,2 ℃, 3 ℃, 4 ℃,5 ℃,6 ℃, 7 ℃, 8 ℃, 9 ℃ or 10 ℃; the time of the condensation reaction is preferably 3 to 8 hours, and may be specifically 3 hours, 3.5 hours, 4 hours, 4.5 hours, 5 hours, 5.5 hours, 6 hours, 6.5 hours, 7 hours, 7.5 hours or 8 hours.
In the synthesis method provided by the present invention, the step b) preferably specifically includes the following steps:
b1 Dissolving the 2- (4-hydroxyphenoxy) propionyl chloride in an organic solvent to obtain an acyl chloride solution; dissolving N-methyl-2-fluoroaniline and an acid binding agent in an organic solvent to obtain a mixed solution;
b2 Dropwise adding the acyl chloride solution into the mixed solution under the condition of cooling and stirring, and carrying out heat preservation reaction after the dropwise adding is finished;
b3 After the heat preservation reaction is finished, the reaction product is subjected to post-treatment to obtain the N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropanamide.
In the synthesis method provided by the invention, in the step b 1), the mass ratio of the organic solvent used for preparing the acyl chloride solution to the organic solvent used for preparing the mixed solution is preferably (0.5-1): 1, specifically may be 0.5:1, 0.55:1, 0.6:1, 0.65:1, 0.7:1, 0.75:1, 0.8:1, 0.85:1, 0.9:1, 0.95:1, or 1:1.
In the synthesis method provided by the invention, in the step b 2), the temperature of the cooling and stirring is preferably-5-10 ℃, more preferably 0-10 ℃, and can be specifically-5 ℃, -4 ℃, -3 ℃, -2 ℃, -1 ℃, 0 ℃,1 ℃,2 ℃, 3 ℃, 4 ℃,5 ℃,6 ℃, 7 ℃, 8 ℃, 9 ℃ or 10 ℃; the dripping time is preferably 1 to 3 hours, more preferably 1 to 2 hours, and can be specifically 1 hour, 1.5 hours, 2 hours, 2.5 hours or 3 hours; the temperature of the heat-preserving reaction is preferably-5 to 10 ℃, more preferably 0 to 10 ℃, and can be specifically-5 ℃, -4 ℃, -3 ℃, -2 ℃, -1 ℃, 0 ℃,1 ℃,2 ℃, 3 ℃, 4 ℃,5 ℃,6 ℃, 7 ℃, 8 ℃, 9 ℃ or 10 ℃; the time of the incubation reaction is preferably 2 to 5 hours, more preferably 2 to 3 hours, and may specifically be 2 hours, 2.5 hours, 3 hours, 3.5 hours, 4 hours, 4.5 hours or 5 hours.
In the synthesis method provided by the present invention, in step b 3), the step of post-treatment preferably specifically includes:
b 3-1) sequentially washing, drying, filtering and desolventizing the reaction product to obtain a crude product;
b 3-2) dissolving the crude product in ethanol, then dripping the obtained ethanol solution into petroleum ether, filtering after dripping, and drying to obtain the N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropanamide refined product.
In the synthesis method provided by the invention, in the step b 3-1), the temperature of the water washing is preferably 45-50 ℃; the number of times of water washing is preferably 2-5 times, and can be specifically 3 times; the single time of the water washing is preferably 20 to 60 minutes, and particularly can be 30 minutes.
In the synthesis method provided by the invention, in the step b 3-1), the drying agent used for drying is preferably anhydrous magnesium sulfate; the mass ratio of the drying agent to the N-methyl-2-fluoroaniline is preferably (1-6): 1, preferably (1 to 3): 1, which may be specifically 1:1, 2:1, 3:1, 4:1, 5:1 or 6:1. The drying time is preferably 20 to 60 minutes, and may be specifically 30 minutes.
In the synthesis method provided by the invention, in the step b 3-1), the solvent removal mode is preferably negative pressure distillation; the vacuum degree of the negative pressure distillation is preferably 0.08-0.095 MPa; the temperature of the negative pressure distillation is preferably 40 to 60 ℃, and may be particularly 50 ℃.
In the synthesis method provided by the invention, in the step b 3-2), the mass ratio of the crude product to ethanol based on the amount of the raw material N-methyl-2-fluoroaniline is preferably (10-20): 60. specifically, the ratio of the raw materials can be 10:60, 12.5:60, 15:60, 17.5:60 or 20:60; the mass ratio of the ethanol to the petroleum ether is preferably 1: (1 to 6), more preferably 1: (2-5), which may be specifically 1:1, 1:2, 1:3, 1:4, 1:5 or 1:6.
In the synthesis method provided by the invention, in the step b 3-2), the dropwise addition is preferably performed under the condition of cooling and stirring; the dripping temperature is preferably-5-10deg.C, more preferably 0-10deg.C, and specifically can be-5 deg.C, -4 deg.C, -3 deg.C, -2 deg.C, -1 deg.C, 0 deg.C, 1 deg.C, 2 deg.C, 3 deg.C, 4 deg.C, 5 deg.C, 6 deg.C, 7 deg.C, 8 deg.C, 9 deg.C or 10deg.C; the time for the dropping is preferably 1 to 4 hours, more preferably 1.5 to 3 hours, and particularly may be 1 hour, 1.5 hours, 2 hours, 2.5 hours, 3 hours, 3.5 hours or 4 hours.
In the synthesis method provided by the invention, the condensation reaction process involved in the step b) is as follows:
the synthesis method provided by the invention uses 2- (4-hydroxy phenoxy) propionic acid as an initial raw material, and the initial raw material is subjected to chlorination reaction with a chlorinating agent under the action of a catalyst in an organic solvent system, and then is subjected to condensation reaction with N-methyl-2-fluoroaniline under the action of an acid binding agent, and the target product N- (2-fluorophenyl) -2- (4-hydroxy phenoxy) -N-methylpropanamide is obtained after post treatment. The synthesis method provided by the invention has the advantages of high reaction yield, high product purity, relatively low price and easy obtainment of raw materials, and is suitable for industrial production. The experimental results show that: the reaction yield of the synthesis method provided by the invention is more than 90%, and the product purity is more than 95%.
For clarity, the following examples are provided in detail.
Example 1
A1000 ml reaction bottle with a tail gas absorbing device, a constant pressure dropwise adding device, a stirring device and a thermometer is prepared, 18.2g (0.10 mol) of 2- (4-hydroxyphenoxy) propionic acid, 273g (2.76 mol) of 1, 2-dichloroethane, 0.3g (0.004 mol) of N, N-dimethylformamide are added, 19g (0.15 mol) of oxalyl chloride is dropwise added under the stirring condition of 55-70 ℃ for 2h, the device removes a low-temperature constant-temperature reaction bath after the dropwise adding is finished, the temperature is raised to reflux, and the reflux stirring reaction is carried out for 3h. After the heat preservation is finished, the device is changed into a negative pressure distillation device, and the temperature is increased to 50 ℃ under the condition of the vacuum degree of 0.08-0.095 MPa, so that the solvent is removed.
60g (0.61 mol) of 1, 2-dichloroethane was added to the above distilled system, and the mixture was placed in a low-temperature constant-temperature reaction bath to reduce the temperature to 0 to 10℃for use. A1000 ml reaction bottle with a tail gas absorbing device, a constant pressure dropwise adding device, a stirring thermometer is placed in a low-temperature constant-temperature reaction bath, 15g (0.12 mol) of N-methyl-2-fluoroaniline, 90g (0.91 mol) of 1, 2-dichloroethane and 50g (0.60 mol) of sodium bicarbonate are added, the temperature is reduced to 0-10 ℃ by stirring, and the solution to be used is moved into the constant pressure dropwise adding device in the device for dropwise adding, wherein the dropwise adding time is 1.5h. After the dripping is finished, stirring and preserving heat for 3 hours under the stirring condition of 0-10 ℃. After the reaction is finished, 100ml of water is added for washing for three times at 45-50 ℃ for 30min each time, the mixture is moved to a separating funnel for liquid separation, the upper water phase is collected and treated, the lower organic phase is shifted to a reaction bottle, 15g (0.125 mol) of anhydrous magnesium sulfate is added for drying for 30min, the filtration is carried out, the device is changed into a negative pressure distillation device, the temperature is raised to 50 ℃ under the condition of the vacuum degree of 0.08-0.095 MPa, the solvent is removed, and 60g of ethanol is added for stirring and dissolving. Placing 500ml reaction bottle with constant pressure dropping device, stirring and thermometer into low temperature constant temperature reaction bath, adding 180g of petroleum ether, dropping ethanol solution into petroleum ether under stirring condition of 0-10 deg.C for 2h, filtering after dropping, obtaining filter cake, and drying to obtain 27.5g of N- (2-fluorophenyl) -2- (4-hydroxy phenoxy) -N-methylpropanamide.
The purity and yield of the obtained product are detected, and the result is: purity 96.89% and yield 92.1%.
In this example, the purity detection was performed in a high performance liquid chromatograph, model LC-16, column ODS-C18 stainless steel column 4.6x250 mm, mobile phase methanol: water: phosphoric acid= (7:3:0.05), column temperature is 35 ℃, detection wavelength is 300nm, and flow rate is 1.0ml/min; the purity detection results are shown in fig. 1 and table 1, fig. 1 is a chromatogram provided in example 1 of the present invention, and table 1 is an analysis result table corresponding to fig. 1:
table 1 example 1 chromatographic results table
| Peak number | Retention time | Peak height | Peak area | Content% |
| 1 | 2.851 | 386 | 2908 | 0.128 |
| 2 | 3.108 | 119 | 1219 | 0.054 |
| 3 | 3.346 | 194 | 2087 | 0.092 |
| 4 | 3.931 | 255 | 2324 | 0.103 |
| 5 | 4.275 | 53 | 254 | 0.011 |
| 6 | 4.576 | 228859 | 2194922 | 96.893 |
| 7 | 7.890 | 4127 | 59697 | 2.635 |
| 8 | 11.889 | 13 | 64 | 0.003 |
| 9 | 13.436 | 16 | 210 | 0.009 |
| 10 | 15.475 | 15 | 171 | 0.008 |
| 11 | 15.787 | 63 | 1340 | 0.059 |
| 12 | 21.952 | 13 | 74 | 0.003 |
| 13 | 28.555 | 11 | 26 | 0.001 |
Example 2
A1000 ml reaction flask with a tail gas absorbing device, a constant pressure dropwise adding device, a stirring thermometer was prepared, 18.2g (0.10 mol) of 2- (4-hydroxyphenoxy) propionic acid, 200g (2.17 mol) of toluene, 0.4g (0.005 mol) of dimethyl sulfoxide, 17.5g (0.15 mol) of thionyl chloride were dropwise added under the stirring condition of 50-65 ℃ for 1.5h, after the dropwise adding was completed, the device removed the low-temperature constant-temperature reaction bath, the temperature was raised to reflux, and the reflux stirring reaction was carried out for 4h. After the heat preservation is finished, the device is changed into a negative pressure distillation device, and the temperature is increased to 50 ℃ under the condition of the vacuum degree of 0.08-0.095 MPa, so that the solvent is removed.
70g (0.76 mol) of toluene is added into the system after distillation, and the mixture is placed in a low-temperature constant-temperature reaction bath and is cooled to 0-5 ℃ for standby. Placing a 1000ml reaction bottle with a tail gas absorbing device, a constant pressure dropwise adding device, a stirring thermometer into a low-temperature constant-temperature reaction bath, adding 12.5g (0.10 mol) of N-methyl-2-fluoroaniline, 100g (1.09 mol) of toluene, adding 30g (0.30 mol) of triethylamine, stirring and cooling to 0-5 ℃, and transferring the solution to be used into the constant pressure dropwise adding device in the device for dropwise adding, wherein the dropwise adding time is 2h. After the dripping is finished, stirring and preserving heat for 2 hours under the stirring condition of 0-5 ℃. After the reaction is finished, 100ml of water is added for washing for three times at 45-50 ℃ for 30min each time, the mixture is moved to a separating funnel for liquid separation, the upper water phase is collected and treated, the lower organic phase is shifted to a reaction bottle, 25g (0.21 mol) of anhydrous magnesium sulfate is added for drying for 30min, the filtration is carried out, the device is changed into a negative pressure distillation device, the temperature is raised to 50 ℃ under the condition of the vacuum degree of 0.08-0.095 MPa, the solvent is removed, and 60g of ethanol is added for stirring and dissolving. Placing 500ml reaction bottle with constant pressure dropping device, stirring and thermometer into low temperature constant temperature reaction bath, adding 240g of petroleum ether, dropping ethanol solution into petroleum ether under stirring condition of 0-5 deg.C for 2.5h, filtering after dropping, obtaining filter cake, and drying to obtain 27.9g of N- (2-fluorophenyl) -2- (4-hydroxy phenoxy) -N-methylpropanamide.
The purity and yield of the obtained product are detected, and the result is: purity 96.02%, yield 92.6%.
In this example, the purity detection was performed in a high performance liquid chromatograph, model LC-16, column ODS-C18 stainless steel column 4.6x250 mm, mobile phase methanol: water: phosphoric acid= (7:3:0.05), column temperature is 35 ℃, detection wavelength is 300nm, and flow rate is 1.0ml/min; the purity detection results are shown in fig. 2 and table 2, fig. 2 is a chromatogram provided in example 2 of the present invention, and table 2 is an analysis result table corresponding to fig. 2:
table 2 example 2 chromatographic results table
| Peak number | Retention time | Peak height | Peak area | Content% |
| 1 | 2.862 | 871.688 | 8294.600 | 0.4229 |
| 2 | 3.148 | 261.667 | 2739.100 | 0.1396 |
| 3 | 3.488 | 422.403 | 3698.700 | 0.1886 |
| 4 | 3.982 | 491.944 | 5392.100 | 0.2749 |
| 5 | 4.362 | 177.558 | 1308.000 | 0.0667 |
| 6 | 4.775 | 175773.938 | 1883563.250 | 96.0240 |
| 7 | 5.642 | 127.615 | 1293.800 | 0.0660 |
| 8 | 6.495 | 186.333 | 1964.900 | 0.1002 |
| 9 | 8.028 | 3143.606 | 48397.199 | 2.4673 |
| 10 | 8.775 | 124.414 | 1380.000 | 0.0704 |
| 11 | 9.028 | 53.857 | 541.100 | 0.0276 |
| 12 | 9.468 | 7.000 | 22.900 | 0.0012 |
| 13 | 9.615 | 5.000 | 28.700 | 0.0015 |
| 14 | 9.735 | 12.929 | 58.300 | 0.0030 |
| 15 | 10.108 | 30.167 | 509.400 | 0.0260 |
| 16 | 11.028 | 12.304 | 101.700 | 0.0052 |
| 17 | 11.322 | 11.286 | 46.500 | 0.0024 |
| 18 | 11.828 | 7.625 | 41.400 | 0.0021 |
| 19 | 12.282 | 6.167 | 27.100 | 0.0014 |
| 20 | 12.602 | 7.714 | 24.400 | 0.0012 |
| 21 | 12.922 | 6.688 | 53.200 | 0.0027 |
The foregoing is merely a preferred embodiment of the present invention and it should be noted that modifications and adaptations to those skilled in the art may be made without departing from the principles of the present invention, which are intended to be comprehended within the scope of the present invention.
Claims (8)
1. The synthesis method of the oxazachlor intermediate comprises the following steps:
a) In the presence of a catalyst, carrying out chlorination reaction on 2- (4-hydroxyphenoxy) propionic acid and a chlorinating agent in an organic solvent to obtain 2- (4-hydroxyphenoxy) propionyl chloride;
in the step a), the chlorinating agent is thionyl chloride and/or oxalyl chloride, and the catalyst is N, N-dimethylformamide and/or dimethyl sulfoxide;
the step a) specifically comprises the following steps: a1 2- (4-hydroxy phenoxy) propionic acid and a catalyst are dissolved in an organic solvent to obtain a mixed solution; a2 Dropwise adding a chlorinating reagent into the mixed solution under the condition of heating and stirring, and heating the mixed solution to reflux after the dropwise adding is finished; a3 After the reflux reaction is finished, removing the organic solvent to obtain 2- (4-hydroxy phenoxy) propionyl chloride;
b) In the presence of an acid binding agent, carrying out condensation reaction on the 2- (4-hydroxyphenoxy) propionyl chloride and N-methyl-2-fluoroaniline in an organic solvent to obtain N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropanamide;
in the step b), the acid binding agent is sodium bicarbonate and/or triethylamine;
the step b) specifically comprises the following steps: b1 Dissolving the 2- (4-hydroxyphenoxy) propionyl chloride in an organic solvent to obtain an acyl chloride solution; dissolving N-methyl-2-fluoroaniline and an acid binding agent in an organic solvent to obtain a mixed solution; b2 Dropwise adding the acyl chloride solution into the mixed solution under the condition of cooling and stirring, and carrying out heat preservation reaction after the dropwise adding is finished; b3 After the heat preservation reaction is finished, the reaction product is subjected to post-treatment to obtain the N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropanamide.
2. The synthetic method according to claim 1, wherein in step a), the molar ratio of the chlorinating agent to 2- (4-hydroxyphenoxy) propionic acid is (0.8-2): 1.
3. the synthetic method according to claim 1, wherein in step a), the molar ratio of the catalyst to 2- (4-hydroxyphenoxy) propionic acid is (0.02-0.1): 1.
4. the synthetic method according to claim 1, wherein in step a), the temperature of the chlorination reaction is 30 ℃ to reflux temperature; the chlorination reaction time is 3-9 h.
5. The synthetic method according to claim 1, wherein the molar ratio of N-methyl-2-fluoroaniline to 2- (4-hydroxyphenoxy) propionic acid is (0.8-2): 1.
6. the synthetic method according to claim 1, wherein in step b), the molar ratio of the acid-binding agent to N-methyl-2-fluoroaniline is (1 to 10): 1.
7. the synthetic method according to claim 1, wherein in step b), the temperature of the condensation reaction is-5 to 10 ℃; the time of the condensation reaction is 3-8 h.
8. The synthesis method according to claim 1, wherein in step b 3), the step of post-treatment specifically comprises:
b 3-1) sequentially washing, drying, filtering and desolventizing the reaction product to obtain a crude product;
b 3-2) dissolving the crude product in ethanol, then dripping the obtained ethanol solution into petroleum ether, filtering after dripping, and drying to obtain the N- (2-fluorophenyl) -2- (4-hydroxyphenoxy) -N-methylpropanamide refined product.
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