CN111217817B - Preparation method of triazolopyrimidine herbicide - Google Patents
Preparation method of triazolopyrimidine herbicide Download PDFInfo
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Abstract
The invention belongs toThe technical field of organic synthesis, in particular to a preparation method of triazolopyrimidine herbicide. The preparation method specifically comprises the following steps: a) reacting a compound with a structure shown in a formula (I) with thiosemicarbazide, and then isomerizing under an alkaline condition to obtain a compound with a structure shown in a formula (II); b) diazotizing the compound with the structure shown in the formula (II) and sodium nitrite, and then mixing the diazotized compound with sodium bisulfite and chloride for reaction to obtain a compound with the structure shown in the formula (III); the chloride comprises cupric chloride and/or cuprous chloride; c) and (3) reacting the compound with the structure shown in the formula (III) with the compound with the structure shown in the formula (IV) to obtain the triazolopyrimidine herbicide with the structure shown in the formula (V). The preparation method provided by the invention has the advantages of mild reaction conditions, low safety risk and good environmental protection.
Description
Technical Field
The invention belongs to the technical field of organic synthesis, and particularly relates to a preparation method of triazolopyrimidine herbicide.
Background
Triazolopyrimidine sulfonamide herbicides were developed by dow agricultural science, usa, and are typical acetolactate synthase inhibitors, and have an important position in the global herbicide market. Common diclosulam, cloransulam, florasulam and the like belong to the herbicides, and have the advantages of high efficiency, high speed, low toxicity and the like.
At present, the traditional preparation process of the triazolopyrimidine sulfonamide herbicide depends on the use of highly toxic and highly toxic products such as carbon disulfide, chlorine and the like, and has extremely high requirements on equipment corrosion, production safety, material storage and the like. And once leakage causes great environmental protection and safety risks, the life health of operators is seriously threatened.
Patent CN1115983 describes a synthesis method of triazolopyrimidine thione, which is to perform a ring-closing reaction between substituted pyrimidine as a raw material and carbon disulfide in methanol to obtain an intermediate. However, the method needs highly toxic raw material carbon disulfide, is extremely easy to deflagrate and has extremely high danger. Moreover, hydrogen peroxide is also needed, the reaction is very violent, the heat release is very large, and the safety risk is higher.
Patents US5163995, CN1039590 describe a process for the preparation of triazolopyrimidine sulfonamides. The preparation method of the intermediate triazolopyrimidinethione is the same as that of the patent. The preparation method needs to undergo steps of hydrazinolysis, cyclization, isomerization, coupling, oxychlorination, condensation and the like, and the route is too long. And the oxychlorination step also needs to use highly toxic chlorine gas, generates a large amount of low-concentration waste acid, has great safety and environmental protection risks and has high requirements on equipment and operation level.
Disclosure of Invention
In view of the above, the invention aims to provide a preparation method of a triazolopyrimidine herbicide, and the preparation method provided by the invention is mild in reaction conditions, low in safety risk and good in environmental friendliness.
The invention provides a preparation method of triazolopyrimidine herbicide, which comprises the following steps:
a) reacting a compound with a structure shown in a formula (I) with thiosemicarbazide, and then isomerizing under an alkaline condition to obtain a compound with a structure shown in a formula (II);
b) carrying out diazotization reaction on the compound with the structure shown in the formula (II) and sodium nitrite, and then mixing the diazotization reaction product with sodium bisulfite and chloride to obtain a compound with the structure shown in the formula (III);
the chloride comprises cupric chloride and/or cuprous chloride;
c) reacting the compound with the structure shown in the formula (III) with the compound with the structure shown in the formula (IV) to obtain the triazolopyrimidine herbicide with the structure shown in the formula (V);
in the formulae (I) to (V), R1is-H, CH3O-、C2H5O-, -SH, -Cl or-Br;
R2is-H, C2H5O-, -F, -Cl or-Br;
R3is-H, CH3O-, -F, or-Cl;
R4is-H, -F, -Cl or-Br;
q, W, X, Y and Z are independently selected from-H, -F, -Cl, -COOH and-COOCH3And at least one of Q, W, X, Y and Z is-F or-Cl.
Preferably, in step a), the molar ratio of the compound with the structure of formula (I) to the thiosemicarbazide is 1: (1-2).
Preferably, in the step a), the reaction temperature is 60-120 ℃; the reaction time is 4-10 h.
Preferably, in step a), the basic conditions are provided by alkali metal carbonates and/or alkali metal alkoxides.
Preferably, in step b), the molar ratio of the compound with the structure of formula (II) to the sodium nitrite is 1: (1.5-5).
Preferably, in the step b), the temperature of the diazotization reaction is-10 ℃; the diazotization reaction time is 1-5 h.
Preferably, in the step b), the molar ratio of the sodium bisulfite to the compound with the structure of the formula (II) is (1-5): 1;
the dosage of the chloride is 0.1-2 times of the mass of the compound with the structure of the formula (II).
Preferably, in the step b), the temperature of the mixing reaction is-20 to 30 ℃; the mixing reaction time is 2-8 h.
Preferably, in step c), the molar ratio of the compound with the structure of formula (III) to the compound with the structure of formula (IV) is 1: (1-3).
Preferably, in the step c), the reaction temperature is 10-50 ℃; the reaction time is 2-8 h.
Compared with the prior art, the invention provides a preparation method of triazolopyrimidine herbicide, which comprises the following steps: a) reacting a compound with a structure shown in a formula (I) with thiosemicarbazide, and then isomerizing under an alkaline condition to obtain a compound with a structure shown in a formula (II); b) carrying out diazotization reaction on the compound with the structure shown in the formula (II) and sodium nitrite, and then mixing the diazotization reaction product with sodium bisulfite and chloride to obtain a compound with the structure shown in the formula (III); the chloride comprises cupric chloride and/or cuprous chloride; c) and (3) reacting the compound with the structure shown in the formula (III) with the compound with the structure shown in the formula (IV) to obtain the triazolopyrimidine herbicide with the structure shown in the formula (V). According to the method provided by the invention, the thiosemicarbazide is adopted to replace carbon disulfide in the traditional technology in the preparation process of the intermediate (II), the reaction condition is mild and controllable, the yield is high, and the problems of high toxicity, high risk and large potential safety hazard in the traditional technology are solved; in the preparation process of the intermediate (III), a sodium nitrite and sodium bisulfite system is adopted to replace a chlorine gas and hydrochloric acid system in the traditional process, the reaction is green and environment-friendly, the dependence of the traditional process on highly toxic chlorine gas is solved, the output of low-concentration waste acid is avoided, the environmental protection pressure is effectively relieved, and the health and potential safety hazards in the preparation process are reduced. The preparation method provided by the invention has the advantages of mild reaction conditions, low safety risk, good environmental protection property and higher product yield, and is very suitable for popularization and use in industrial production.
Drawings
In order to more clearly illustrate the embodiments of the present invention or the technical solutions in the prior art, the drawings used in the description of the embodiments or the prior art will be briefly described below, it is obvious that the drawings in the following description are only embodiments of the present invention, and for those skilled in the art, other drawings can be obtained according to the provided drawings without creative efforts.
FIG. 1 is a mass spectrum provided in example 1 of the present invention;
FIG. 2 is a liquid chromatography spectrum provided in example 1 of the present invention;
FIG. 3 is a mass spectrum provided in example 2 of the present invention;
FIG. 4 is a liquid chromatography spectrum provided in example 2 of the present invention;
FIG. 5 is a mass spectrum provided in example 4 of the present invention;
FIG. 6 is a liquid chromatography spectrum provided in example 4 of the present invention.
Detailed Description
The technical solutions in the embodiments of the present invention are clearly and completely described below, and it is obvious that the described embodiments are only a part of the embodiments of the present invention, and not all embodiments. All other embodiments, which can be derived by a person skilled in the art from the embodiments given herein without making any creative effort, shall fall within the protection scope of the present invention.
The invention provides a preparation method of triazolopyrimidine herbicide, which comprises the following steps:
a) reacting a compound with a structure shown in a formula (I) with thiosemicarbazide, and then isomerizing under an alkaline condition to obtain a compound with a structure shown in a formula (II);
b) carrying out diazotization reaction on the compound with the structure shown in the formula (II) and sodium nitrite, and then mixing the diazotization reaction product with sodium bisulfite and chloride to obtain a compound with the structure shown in the formula (III);
the chloride comprises cupric chloride and/or cuprous chloride;
c) reacting the compound with the structure shown in the formula (III) with the compound with the structure shown in the formula (IV) to obtain the triazolopyrimidine herbicide with the structure shown in the formula (V);
in the formulae (I) to (V), R1is-H, CH3O-、C2H5O-, -SH, -Cl or-Br;
R2is-H, C2H5O-, -F, -Cl or-Br;
R3is-H, CH3O-, -F, or-Cl;
R4is-H, -F, -Cl or-Br;
q, W, X, Y and Z are independently selected from-H, -F, -Cl, -COOH and-COOCH3And at least one of Q, W, X, Y and Z is-F or-Cl.
In the preparation method provided by the invention, the compound with the structure shown in the formula (I) is firstly reacted with thiosemicarbazide. Wherein, the mol ratio of the compound with the structure of formula (I) to the thiosemicarbazide is preferably 1: (1-2), more preferably 1: (1.1-1.5), specifically 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; the reaction is preferably carried out in an organic solvent, preferably comprising one or more of methanol, ethanol, butanol, chloroform, Dimethylformamide (DMF) and ethyl acetate, more preferably ethanol and/or butanol; the reaction temperature is preferably 60 to 120 ℃, more preferably 80 to 90 ℃, and specifically can be 60 ℃, 65 ℃, 70 ℃, 75 ℃, 80 ℃, 85 ℃, 90 ℃, 95 ℃, 100 ℃, 105 ℃, 110 ℃, 115 ℃ or 120 ℃; the reaction time is preferably 4-10 h, and specifically can be 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h, 8h, 8.5h, 9h, 9.5h or 10 h.
In the preparation method provided by the invention, after the reaction of the compound with the structure shown in the formula (I) and thiosemicarbazide is finished, the reaction product is isomerized under the alkaline condition. Wherein the basic conditions are preferably provided by alkali metal carbonates and/or alkali metal alkoxides, such as one or more of sodium carbonate, potassium carbonate, sodium methoxide, sodium ethoxide and sodium tert-butoxide, preferably sodium methoxide; the pH value of the alkaline condition is preferably 10-11; the isomerization temperature is preferably 5 to 20 ℃, and specifically may be 5 ℃,6 ℃, 7 ℃, 8 ℃, 9 ℃, 10 ℃, 11 ℃, 12 ℃, 13 ℃, 14 ℃, 15 ℃, 16 ℃, 17 ℃, 18 ℃, 19 ℃ or 20 ℃; the time of the isomerization reaction is preferably 1-5 h, and specifically can be 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h or 5 h. In the present invention, the specific operating steps for carrying out said isomerization preferably comprise: firstly, regulating the temperature of the reaction product to the required isomerization temperature, then dropwise adding a solution of alkali metal carbonate and/or alkali metal alkoxide into the reaction product, and after the dropwise adding is finished, preserving the temperature to perform reaction to complete isomerization. Wherein the concentration of the alkali metal salt in the solution is preferably 15-40 wt%, and specifically can be 15 wt%, 17 wt%, 20 wt%, 23 wt%, 25 wt%, 27 wt%, 30 wt%, 32 wt%, 35 wt%, 37 wt% or 40 wt%; the time consumed for dropwise adding is preferably 0.5-2 h, and specifically can be 0.5h, 1h, 1.5h or 2 h. In the invention, after the isomerization reaction is finished, the reaction product is post-treated to obtain the compound with the structure of the formula (II). Wherein the step of post-processing preferably comprises: firstly, adding acid to adjust the pH value of a reaction product, then adding water to crystallize, filtering, washing and drying in sequence to obtain the compound with the structure of the formula (II). In the post-treatment process, the acid is preferably hydrochloric acid; the pH value is preferably adjusted to 7-8; the washing mode is preferably water washing; the drying mode is preferably drying.
In the preparation method provided by the invention, after the compound with the structure of the formula (II) is obtained, the diazotization reaction is carried out on the compound with the structure of the formula (II) and sodium nitrite. Wherein the molar ratio of the compound with the structure of the formula (II) to the sodium nitrite is preferably 1: (1.5-5), more preferably 1: (1.5-2), specifically 1:1.5, 1:1.6, 1:1.7, 1:1.8, 1:1.9, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9, 1:3, 1:3.1, 1:3.2, 1:3.3, 1:3.4, 1:3.5, 1:3.6, 1:3.7, 1:3.8, 1:3.9, 1:4, 1:4.1, 1:4.2, 1:4.3, 1:4.4, 1:4.5, 1:4.6, 1:4.7, 1:4.8, 1:4.9, or 1: 5; the diazotization reaction is preferably carried out in an acid solution, and the acid solution is preferably hydrochloric acid aqueous solution, sulfuric acid aqueous solution and acetic acid aqueous solution, and is more preferably sulfuric acid aqueous solution; the temperature of the diazotization reaction is preferably-10 ℃, more preferably 0-5 ℃, and specifically can be-10 ℃, -9 ℃, -8 ℃, -7 ℃, -6 ℃, -5 ℃, -4 ℃, -3 ℃, -2 ℃, -1 ℃, 0 ℃, 1 ℃,2 ℃, 3 ℃,4 ℃,5 ℃,6 ℃, 7 ℃, 8 ℃, 9 ℃ or 10 ℃; the diazotization reaction time is preferably 1-5 h, and specifically can be 1h, 1.5h, 2h, 2.5h, 3h, 3.5h, 4h, 4.5h or 5 h. In the present invention, the specific operation steps for carrying out the diazotization reaction preferably include: adding the compound with the structure shown in the formula (II) into acid liquor, then adjusting the temperature of a mixed system to the required temperature of diazotization reaction, then dropwise adding a sodium nitrite aqueous solution into the mixed system, and after dropwise adding, preserving the temperature and reacting to complete diazotization. Wherein the concentration of the sodium nitrite aqueous solution is preferably 20-40 wt%, and specifically can be 20 wt%, 25 wt%, 30 wt%, 35 wt% or 40 wt%. In the invention, after the diazotization reaction is finished, diazotization solution is obtained. In the present invention, in order to destroy the sodium nitrite remaining in the diazo liquid, it is preferable to add a small amount of urea to the diazo liquid obtained by the reaction.
In the preparation method provided by the invention, after the diazo liquid is obtained, the diazo liquid is mixed with sodium bisulfite and chloride for reaction. Wherein the molar ratio of the sodium bisulfite to the raw material for preparing the diazo liquid, namely the compound with the structure of the formula (II), is preferably (1-5): 1, more preferably (2-3): 1, specifically 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, 2:1, 2.1:1, 2.2:1, 2.3:1, 2.4:1, 2.5:1, 2.6:1, 2.7:1, 2.8:1, 2.9:1, 3:1, 3.1:1, 3.2:1, 3.3:1, 3.4:1, 3.5:1, 3.6:1, 3.7:1, 3.8:1, 3.9:1, 4:1, 4.1:1, 4.2:1, 4.3:1, 4.4:1, 4.5:1, 4.7:1, 4.8:1, 4.9:1, 4.1, 4:1, 4.3:1, 4.4:1, 4:1, 4.5:1, 4.1, 4.8:1, 4.9:1, or 1; the amount of the chloride is preferably 0.1 to 2 times, more preferably 0.5 to 1 time, specifically 0.1 time, 0.2 time, 0.3 time, 0.4 time, 0.5 time, 0.6 time, 0.7 time, 0.8 time, 0.9 time, 1 time, 1.1 time, 1.2 times, 1.3 times, 1.4 times, 1.5 times, 1.6 times, 1.7 times, 1.8 times, 1.9 times or 2 times of the mass of the compound having the structure of formula (II) used for preparing the diazonium solution; the temperature of the mixing reaction is preferably-20-30 ℃, more preferably 0-10 ℃, and specifically can be-20 ℃, 15 ℃, 10 ℃,5 ℃, 0 ℃,5 ℃, 10 ℃, 15 ℃, 20 ℃, 25 ℃ or 30 ℃; the mixing reaction time is preferably 2-8 h, and specifically can be 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h or 8 h. In the present invention, the specific operation steps for carrying out the mixing reaction preferably include: and adding sodium bisulfite into the chloride solution, controlling the temperature of the system to be the required temperature of the mixing reaction, dropwise adding the diazo liquid into the system, and preserving heat for reaction after dropwise adding. Wherein the components of the chloride solution comprise chloride (cupric chloride and/or cuprous chloride), acid and organic solvent, the acid can be selected from hydrochloric acid, and the organic solvent can be selected from dichloromethane; before adding sodium bisulfite to the chloride solution, the temperature of the chloride solution is preferably first adjusted to the desired temperature for the mixing reaction; the time consumption for dropwise adding the diazo liquid is preferably 0.5-2 h, and specifically can be 0.5h, 1h, 1.5h or 2 h. In the invention, after the mixing reaction is finished, the reaction product is kept stand, and after the reaction product is layered, the lower organic phase is collected to obtain a solution in which the compound with the structure of the formula (III) is dissolved. In the present invention, after the solution in which the compound having the structure of formula (III) is dissolved is obtained, the solution may be further post-treated to obtain a pure compound having the structure of formula (III). Wherein the step of further post-processing preferably comprises: and (3) sequentially washing, drying and desolventizing the solution to obtain a pure compound with the structure of the formula (III).
In the preparation method provided by the invention, the solution in which the compound with the structure of the formula (III) is dissolved or the pure product of the compound with the structure of the formula (III) is obtained and then is reacted with the compound with the structure of the formula (IV). Wherein the molar ratio of the compound with the structure of formula (III) to the compound with the structure of formula (IV) is preferably 1: (1-3), more preferably 1: (1.5-2), specifically 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, 1:2, 1:2.1, 1:2.2, 1:2.3, 1:2.4, 1:2.5, 1:2.6, 1:2.7, 1:2.8, 1:2.9 or 1: 3; the reaction is preferably carried out in the presence of a catalyst, which can be sodium carbonate, potassium carbonate, triethylamine, trimethylamine or the compound of formula (IV) itself, preferably the compound of formula (IV) itself; the reaction temperature is preferably 10-50 ℃, more preferably 30-40 ℃, and specifically can be 10 ℃, 15 ℃, 20 ℃, 25 ℃, 30 ℃, 35 ℃, 40 ℃, 45 ℃ or 50 ℃; the reaction time is preferably 2-8 h, and specifically can be 2h, 2.5h, 3h, 3.5h, 4h, 4.5h, 5h, 5.5h, 6h, 6.5h, 7h, 7.5h or 8 h. In the present invention, taking the solution in which the compound having the structure of formula (III) is dissolved as an example, the specific operation steps for performing the reaction preferably include: the method comprises the steps of distilling the solution under reduced pressure until no water is separated from the fraction, cooling the solution, adding 1, 2-propylene glycol into the solution to separate out a white solid, adding a compound with a structure shown in formula (IV) and an organic solvent, heating to the reaction temperature, and carrying out heat preservation reaction. Wherein the solution is preferably cooled to 10-30 ℃, and specifically, the temperature of the solution can be 10 ℃, 15 ℃, 20 ℃, 25 ℃ or 30 ℃; the organic solvent is preferably dichloromethane. In the invention, after the reaction is finished, the reaction product is subjected to post-treatment to obtain the triazolopyrimidine herbicide with the structure of formula (V). Wherein the step of post-processing preferably comprises: firstly, adding water into the reaction product for crystallization, and then filtering to obtain a crude product; and then transferring the crude product into methanol for pulping, and then sequentially filtering, washing and drying to obtain the high-purity compound with the structure shown in the formula (V).
According to the method provided by the invention, the thiosemicarbazide is adopted to replace carbon disulfide in the traditional technology in the preparation process of the intermediate (II), the reaction condition is mild and controllable, the yield is high, and the problems of high toxicity, high risk and large potential safety hazard in the traditional technology are solved; in the preparation process of the intermediate (III), a sodium nitrite and sodium bisulfite system is adopted to replace a chlorine gas and hydrochloric acid system in the traditional process, the reaction is green and environment-friendly, the dependence of the traditional process on highly toxic chlorine gas is solved, the output of low-concentration waste acid is avoided, the environmental protection pressure is effectively relieved, and the health and potential safety hazards in the preparation process are reduced. The preparation method provided by the invention has the advantages of mild reaction conditions, low safety risk, good environmental protection property and higher product yield, and is very suitable for popularization and use in industrial production.
For the sake of clarity, the following examples are given in detail.
Example 1
Preparation of 5-methoxy-8-fluoro- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine
100g of ethanol, 25g of 2-methoxy-4-chloro-5-fluoropyrimidine and 28g of thiosemicarbazide are added into a four-neck flask, and the mixture is heated and refluxed for reaction for 6 hours. After the reaction was completed, the reaction temperature was lowered to 10 ℃. Then, 37g of a 27 wt% sodium methoxide methanol solution was added dropwise over 1 hour. After the dropwise addition is completed, adjusting the pH value of the system to 10-11, and reacting for 2 hours under the condition of heat preservation.
After the reaction was completed, 25g of hydrochloric acid having a concentration of 30 wt% was added dropwise to adjust the pH of the system to 7 to 8, and a large amount of a yellowish white solid was precipitated. Then 100g of water is added, stirred, crystallized, filtered, washed and dried to obtain 25.2g of product with the purity of 95%.
The product was analyzed by mass spectrometry and liquid chromatography. Wherein, the chromatographic analysis involves the following condition parameters:
the instrument model is as follows: agilent technologies 1260; a chromatographic column: c18 reversed phase column, 250X 4.6 mm; a detector: an ultraviolet detector; detection wavelength: 260 nm; mobile phase: [ methanol: 0.5% aqueous phosphoric acid ] ═ 50: 50; flow rate: 1.0 mL/min.
The mass spectrometry result is m/z: 183.1 (100%), 184.1 (10%), detailed spectrum is shown in FIG. 1, FIG. 1 is the mass spectrum provided in example 1 of the present invention; the liquid chromatography result is shown in fig. 2, and fig. 2 is a liquid chromatography spectrum provided in example 1 of the present invention.
Example 2
Preparation of 5-ethoxy-7-fluoro- [1,2,4] triazolo [1,5-C ] pyrimidin-2-amine
In a four-necked flask, 90g of butanol was added, and then 30g of 2-ethoxy-4, 6-difluoropyrimidine, 34g of thiosemicarbazide, and 38g of triethylamine (acid-binding agent) were added. After the addition, the temperature is raised and the reflux reaction is carried out for 8 hours. After the reaction was completed, the reaction temperature was lowered to 5 ℃. Then, 77g of a 20 wt% sodium ethoxide solution in ethanol was added dropwise over 1 hour. And after the dropwise addition is finished, adjusting the pH value of the system to 10-11, and reacting for 3 hours in a heat preservation manner.
After the reaction was completed, 30g of hydrochloric acid having a concentration of 30 wt% was added dropwise to adjust the pH of the system to 7 to 8, and a large amount of white solid was precipitated. Then 200g of water is added, stirred, crystallized, filtered, washed and dried to obtain 29g of product with the purity of 96%.
The above products were analyzed by mass spectrometry and liquid chromatography. Wherein, the chromatographic analysis involves the following condition parameters:
the instrument model is as follows: agilent technologies 1260; a chromatographic column: c18 reversed phase column, 250X 4.6 mm; a detector: an ultraviolet detector; detection wavelength: 230 nm; mobile phase: [ methanol: 0.5% aqueous phosphoric acid ] ═ 50: 50; flow rate: 1.0 mL/min.
The mass spectrometry result is m/z: 197.1 (100%), 198.1 (10%), wherein the detailed spectrum is shown in FIG. 3, and FIG. 3 is the mass spectrum provided in example 2 of the present invention; the liquid chromatography result is shown in fig. 4, and fig. 4 is a liquid chromatography spectrum provided in example 2 of the present invention.
Example 3
Preparation of 5-methoxy-8-fluoro- [1,2,4] triazolo [1,5-C ] pyrimidine-2-sulfonyl chloride
60g of hydrochloric acid with the concentration of 30 weight percent and 100g of water are added into a four-neck flask, after the mixture is uniformly stirred, 30g of the product obtained in the example 1 is slowly added, then the temperature of the system is reduced to 0 ℃, 41.5g of the prepared 30 weight percent sodium nitrite aqueous solution is slowly dripped, and the dripping time is 2 hours. The temperature is kept constant in the dropping process, and the reaction is carried out for 2 hours under the condition of heat preservation after the dropping is finished. Then a small amount of urea is added to destroy the sodium nitrite residue. Stirring and storing at low temperature for later use.
In another reaction flask, 30g of hydrochloric acid with the concentration of 30 wt%, 100g of dichloromethane and 10g of cuprous chloride are added, stirred and mixed uniformly, the temperature is reduced to 10 ℃, and 18.8g of sodium bisulfite is slowly added. Maintaining the reaction temperature at 10-15 ℃, and slowly dripping the obtained diazonium solution. The dropwise addition lasts for 1 hour, and the reaction is continued for 3 hours after the dropwise addition is finished.
After the reaction was completed, the layers were allowed to stand and separate, and the upper aqueous phase was extracted once with dichloromethane. The combined organic phases were washed once with water, dried and then desolventized to give 41g of the target product with a purity of 93%.
In general, we do not isolate the intermediate from solution, but rather perform the subsequent reaction directly in solution.
Example 4
Preparation of florasulam
In a four-necked flask, 140g of a methylene chloride solution of 5-methoxy-8-fluoro- [1,2,4] triazolo [1,5-C ] pyrimidine-2-sulfonyl chloride obtained in example 3 was charged and the content of 5-methoxy-8-fluoro- [1,2,4] triazolo [1,5-C ] pyrimidine-2-sulfonyl chloride in the solution was about 38g, followed by distillation under reduced pressure until the distillate was separated anhydrous. After the distillation was completed, the temperature of the system was lowered to 20 ℃ and then 40g of 1, 2-propanediol was added, and a large amount of white solid was precipitated. Then, 46g of 2, 6-difluoroaniline and 40g of dichloromethane were added. Heating to 40 ℃ and keeping the temperature for reaction for 5 h. Adding 100g of water, stirring for crystallization, and filtering to obtain a crude florasulam product. And (3) pulping the crude product in 100g of methanol, filtering, washing and drying to obtain 51g of finished product with the purity of 98%.
The above products were analyzed by mass spectrometry and liquid chromatography. Wherein, the chromatographic analysis involves the following condition parameters:
the instrument model is as follows: agilent technologies 1260; a chromatographic column: c18 reversed phase column, 250X 4.6 mm; a detector: an ultraviolet detector; detection wavelength: 254 nm; mobile phase: [ methanol: 0.5% aqueous phosphoric acid ] ═ 50: 50; flow rate: 1.0 mL/min.
The mass spectrometry result is m/z: 358.1 (100%), 359.3 (11%), wherein the detailed spectrum is shown in FIG. 5, and FIG. 5 is the mass spectrum provided in example 4 of the present invention; the liquid chromatography analysis result is shown in fig. 6, and fig. 6 is a liquid chromatography spectrum provided in example 4 of the present invention.
The foregoing is only a preferred embodiment of the present invention, and it should be noted that, for those skilled in the art, various modifications and decorations can be made without departing from the principle of the present invention, and these modifications and decorations should also be regarded as the protection scope of the present invention.
Claims (9)
1. A preparation method of triazolopyrimidine herbicide comprises the following steps:
a) reacting a compound with a structure shown in a formula (I) with thiosemicarbazide, and then isomerizing under an alkaline condition to obtain a compound with a structure shown in a formula (II);
b) carrying out diazotization reaction on the compound with the structure shown in the formula (II) and sodium nitrite, and then mixing the diazotization reaction product with sodium bisulfite and chloride to obtain a compound with the structure shown in the formula (III);
the chloride comprises cupric chloride and/or cuprous chloride;
c) reacting the compound with the structure shown in the formula (III) with the compound with the structure shown in the formula (IV) to obtain the triazolopyrimidine herbicide with the structure shown in the formula (V);
in the formulae (I) to (V), R1is-H, CH3O-、C2H5O-, -SH, -Cl or-Br;
R2is-H, C2H5O-, -F, -Cl or-Br;
R3is-H, CH3O-, -F, or-Cl;
R4is-F, -Cl or-Br;
q, W, X, Y and Z are independently selected from-H, -F, -Cl, -COOH and-COOCH3And at least one of Q, W, X, Y and Z is-F or-Cl;
in the step a), the mol ratio of the compound with the structure shown in the formula (I) to the thiosemicarbazide is 1: (1-2).
2. The preparation method according to claim 1, wherein in the step a), the temperature of the reaction is 60-120 ℃; the reaction time is 4-10 h.
3. The process according to claim 1, wherein in step a), the basic conditions are provided by alkali metal carbonates and/or alkali metal alkoxides.
4. The preparation method according to claim 1, wherein in step b), the molar ratio of the compound having the structure of formula (II) to the sodium nitrite is 1: (1.5-5).
5. The preparation method according to claim 1, wherein in the step b), the temperature of the diazotization reaction is-10 to 10 ℃; the diazotization reaction time is 1-5 h.
6. The preparation method according to claim 1, wherein in the step b), the molar ratio of the sodium bisulfite to the compound with the structure of formula (II) is (1-5): 1;
the dosage of the chloride is 0.1-2 times of the mass of the compound with the structure of the formula (II).
7. The preparation method according to claim 1, wherein in the step b), the temperature of the mixing reaction is-20 to 30 ℃; the mixing reaction time is 2-8 h.
8. The method according to claim 1, wherein in step c), the molar ratio of the compound having the structure of formula (III) to the compound having the structure of formula (IV) is 1: (1-3).
9. The preparation method according to claim 1, wherein in step c), the reaction temperature is 10-50 ℃; the reaction time is 2-8 h.
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Family Cites Families (17)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US5010195A (en) * | 1988-05-25 | 1991-04-23 | The Dow Chemical Company | Herbicidal alkoxy-1,2,4-triazolo(1,5-c)primidine-2-sulfonamides |
| DK100392D0 (en) * | 1992-08-10 | 1992-08-10 | Gea Farmaceutisk Fabrik As | 3- AND 5-SUBSTITUTED 1,2,3,4-OXATRIAZOL-5 IMIN COMPOUNDS AND PROCEDURES FOR THE PRODUCTION THEREOF, PHARMACEUTICAL PREPARATION CONTAINING THESE COMPOUNDS AND THE USE OF THE COMPOUNDS FOR PREPARATION |
| US5461153A (en) * | 1993-11-05 | 1995-10-24 | Dowelanco | 2-alkoxy-4-hydrazinopyrimidine compounds |
| US5488109A (en) * | 1993-11-05 | 1996-01-30 | Dowelanco | 5-alkoxy[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)--thione compounds and their use in the preparation of and 2-chlorosulfonyl-5-alkoxy[1,2,4]triazolo[1,5-c]-pyrimidine compounds |
| AU723666B2 (en) * | 1996-09-24 | 2000-08-31 | Dow Agrosciences Llc | N-({1,2,4} triazoloazinyl)benzenesulfonamide and pyridinesulfonamide compounds and their use as herbicides |
| DE60102215T2 (en) * | 2000-11-03 | 2004-07-22 | Dow Agrosciences Llc, Indianapolis | N- (5,7-DIMETHOXY [1,2,4] TRIAZOLO [1,5-A] PYRIMIDIN-2-YL) ARYLSULFONAMIDE COMPOUNDS AND THE USE THEREOF AS HERBICIDES |
| CN102153556B (en) * | 2010-12-14 | 2013-03-27 | 北京颖泰嘉和生物科技有限公司 | Triazolopyrimidine compound and preparation method thereof |
| CN102617577A (en) * | 2012-02-17 | 2012-08-01 | 北京颖新泰康国际贸易有限公司 | Preparation method of triazolopyrimidine sulfonyl chloride type compound |
| CN103232453A (en) * | 2013-04-18 | 2013-08-07 | 黑龙江大学 | Synthesizing method of 2-amino-5,8-dimethoxy[1,2,4]-triazolo[1,5-c]-pyrimidine |
| CN103509027B (en) * | 2013-10-30 | 2016-01-20 | 江苏省农用激素工程技术研究中心有限公司 | The preparation method of florasulam |
| CN103724353B (en) * | 2013-12-12 | 2015-12-30 | 江苏富鼎化学有限公司 | The improvement synthetic method of penoxsuam |
| CN103923086B (en) * | 2014-03-31 | 2016-08-31 | 齐鲁工业大学 | A kind of preparation method of 5-alkoxyl-1,2,4-triazole [4,3-c] pyrimidine-3 (2H)-thioketone |
| CN105294697B (en) * | 2015-11-20 | 2019-07-09 | 北京英力精化技术发展有限公司 | The synthetic method of 2- amino -5,8- dimethoxy [1,2,4] triazol [1,5-c] pyrimidine |
| CN107602566B (en) * | 2017-09-26 | 2019-11-01 | 江苏省农用激素工程技术研究中心有限公司 | The synthetic method of florasulam intermediate |
| US20190106428A1 (en) * | 2017-10-10 | 2019-04-11 | Dow Agrosciences Llc | Method of preparation of florasulam |
| CN110563735B (en) * | 2019-09-27 | 2022-03-29 | 江苏好收成韦恩农化股份有限公司 | Method for preparing florasulam |
| CN113402472B (en) * | 2021-06-16 | 2022-09-13 | 山东潍坊润丰化工股份有限公司 | Synthetic method of sulfentrazone intermediate |
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