Method for synthesizing prothioconazole

Abstract

The invention relates to a method for synthesizing prothioconazole, which comprises the following steps: by taking 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chloro-phenyl)-3-(4, 5-dihydro-1, 2, 4-triazolidine-5-thiocarbonyl-1-yl)-propan-2-ol as a raw material and oxygen as an oxidant, carrying out oxidation reaction in the presence of a composite catalyst, an organic solvent and water to prepare prothioconazole, the composite catalyst comprises a nitroxide free radical compound or a compound capable of generating nitroxide free radicals in situ in the reaction process and a transition metal catalyst. According to the method, the nitroxide free radical compound or the compound capable of generating nitroxide free radicals in situ in the reaction process and the transition metal catalyst are compounded for use, and unpaired electrons in the molecular structure of the nitroxide free radical compound or the compound capable of generating nitroxide free radicals in situ in the reaction process have inherent free radical characteristics; the transition metal catalyst can participate in the free radical reaction through transition metal valence state change, ligand dissociation and other mechanisms, circulation is formed, and then the yield is increased.

Description

Technical Field

[0001] This invention relates to the field of chemical technology, and in particular to a method for synthesizing prothioconazole. Background Technology

[0002] Prothioconazole is a broad-spectrum triazole thione fungicide, mainly used to control numerous diseases in cereal, wheat, and legume crops. The introduction of a thione structure into the molecule gives prothioconazole a broader spectrum of fungicidal activity. As shown below, prothioconazole exists in two tautomers: the thione form and the mercapto form.

[0003]

[0004] (1) Thione form (2) Mercapto form In related technologies, the ferric chloride oxidation method is commonly used to synthesize prothioconazole. Specifically, alcohols are used as solvents and ferric chloride as an oxidant to oxidize the intermediate 2-(1-chloro-cyclopropane)-1-(2-chlorophenyl)-2-hydroxy-3-(1,2,4-triazolidine-5-thion-1-yl)propane (referred to as the thioether intermediate) to prothioconazole. According to theoretical calculations, the synthesis of one ton of prothioconazole requires 945 kg of ferric chloride and generates 738 kg of ferrous chloride and 212 kg of hydrogen chloride. The large amounts of ferrous chloride and waste acid generated are difficult to treat and are environmentally unfriendly.

[0005] For example, one method discloses a procedure for preparing prothioconazole. Specifically, 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol, toluene, and an aqueous solution of ferric chloride are mixed, heated to 30-40°C, cooled to 10-20°C, filtered, dried, and the filtrate is separated into an organic phase and an aqueous phase. A small amount of concentrated hydrochloric acid is added to the aqueous phase under stirring, while maintaining the temperature at 30-40°C. Hydrogen peroxide solution is then slowly added, and the system is heated to approximately 85°C and held for 2 hours. Water is removed under reduced pressure, and a small amount of fresh ferric chloride is added to maintain the total weight of the ferric chloride solution at approximately 35 g and the total molar concentration at approximately 66.0 mmol. This solution is then used in the next oxidation reaction. However, this method for synthesizing prothioconazole generates a large amount of wastewater containing hydrochloric acid and iron ions. Summary of the Invention

[0006] This invention provides a method for synthesizing prothioconazole, thereby solving the technical problem of generating large amounts of wastewater containing hydrochloric acid and iron ions during the synthesis of prothioconazole.

[0007] This invention provides a method for synthesizing prothioconazole, using 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol as a raw material, and oxygen as an oxidant, in the presence of a composite catalyst, an organic solvent, and water, to obtain the prothioconazole through an oxidation reaction. The composite catalyst includes nitroxide free radical compounds or compounds that can generate nitroxide free radicals in situ during the reaction, and a transition metal catalyst.

[0008] In embodiments of the present invention, the nitroxide free radical compound or the compound that can generate nitroxide free radicals in situ during the reaction is selected from at least one of 2,2,6,6-tetramethylpiperidine oxide, 4-hydroxy-2,2,6,6-tetramethylpiperidine oxide, N-hydroxyphthalimide, and N-acetoxyphthalimide.

[0009] In this embodiment of the invention, the transition metal catalyst is selected from at least one of iron salt catalysts, cobalt salt catalysts, and manganese salt catalysts.

[0010] In this embodiment of the invention, the molar ratio of the nitroxide radical compound or the compound that can generate nitroxide radicals in situ during the reaction to the transition metal catalyst is 1-20:1.

[0011] In an embodiment of the present invention, the molar ratio of the composite catalyst to the 2-(1-chloro-cyclopropane-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-propane-2-ol is 2-20:100.

[0012] In this embodiment of the invention, the organic solvent is selected from at least one of halogenated hydrocarbons, ketones, and esters.

[0013] In this embodiment of the invention, the oxidation reaction is carried out at a temperature of 50-80°C.

[0014] In this embodiment of the invention, a purification step is included after the oxidation reaction.

[0015] In this embodiment of the invention, the purification includes: allowing the phase to stand and separate, washing the oil phase obtained by separation with water, distilling, cooling and crystallizing, filtering, and drying.

[0016] In this embodiment of the invention, the temperature is reduced to less than or equal to 5°C.

[0017] The beneficial effects of this invention are: In this invention, oxygen is used instead of ferric chloride as the oxidant, which avoids the technical problem of generating a large amount of wastewater containing hydrochloric acid and iron ions that occurs when ferric chloride is used as an oxidant in the synthesis of prothioconazole in the prior art.

[0018] In this invention, a nitroxide radical compound or a compound that can generate nitroxide radicals in situ during the reaction is used in combination with a transition metal catalyst. The unpaired electrons in the molecular structure of the nitroxide radical compound have inherent free radical characteristics and can participate in the free radical reaction. The transition metal catalyst enters the free radical reaction through mechanisms such as transition metal valence state change and ligand dissociation, forming a cycle and thereby improving the yield. Attached Figure Description

[0019] The accompanying drawings, which are incorporated in and form part of this specification, illustrate embodiments consistent with this application and, together with the description, serve to explain the principles of this application. It is obvious that the drawings described below are merely some embodiments of this application, and those skilled in the art can obtain other drawings based on these drawings without any inventive effort.

[0020] In the attached diagram: Figure 1 This is a flowchart of the method for synthesizing prothioconazole in this invention. Detailed Implementation

[0021] The technical solutions of the embodiments of the present invention will be clearly and completely described below with reference to the accompanying drawings. Obviously, the described embodiments are only a part of the embodiments of the present invention, and not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0022] This invention provides a method for synthesizing prothioconazole. Using 2-(1-chloro-cyclopropyl-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol as a raw material, and oxygen as an oxidant, prothioconazole is obtained through an oxidation reaction in the presence of a composite catalyst, an organic solvent, and water. The composite catalyst includes nitroxide free radical compounds or compounds that can generate nitroxide free radicals in situ during the reaction, and a transition metal catalyst. The reaction principle is as follows: ; In the formula, catalyst represents a catalyst (i.e., a composite catalyst).

[0023] In this invention, oxygen is used instead of ferric chloride as the oxidant, which avoids the technical problem of generating large amounts of wastewater containing hydrochloric acid and iron ions, which is a consequence of using ferric chloride as an oxidant in the synthesis of prothioconazole in existing technologies. In this invention, a nitroxide radical compound or a compound that can generate nitroxide radicals in situ during the reaction is used in combination with a transition metal catalyst. The unpaired electrons in the molecular structure of the nitroxide radical compound possess inherent free radical characteristics and can participate in free radical reactions. The transition metal catalyst enters the free radical reaction through mechanisms such as transition metal valence state changes and ligand dissociation, forming a cycle and thus improving the yield.

[0024] In embodiments of the present invention, the nitroxide free radical compound or the compound that can generate nitroxide free radicals in situ during the reaction is selected from at least one of 2,2,6,6-tetramethylpiperidine oxide, 4-hydroxy-2,2,6,6-tetramethylpiperidine oxide, N-hydroxyphthalimide, and N-acetoxyphthalimide.

[0025] In this embodiment of the invention, the transition metal catalyst is selected from at least one of iron salt catalysts, cobalt salt catalysts, and manganese salt catalysts.

[0026] In this embodiment of the invention, the iron salt catalyst is selected from at least one of ferric nitrate, ferric sulfate, and ferric acetate.

[0027] In this embodiment of the invention, the cobalt salt catalyst is selected from at least one of cobalt acetate, cobalt chloride, cobalt sulfate, and cobalt acetylacetonate.

[0028] In this embodiment of the invention, the manganese salt catalyst is selected from at least one of manganese acetate, manganese sulfate, and manganese chloride.

[0029] In embodiments of the present invention, the molar ratio of the nitroxide radical compound or the compound that can generate nitroxide radicals in situ during the reaction to the transition metal catalyst is 1-20:1, preferably 1-10:1.

[0030] In this embodiment of the invention, the molar ratio of the composite catalyst to 2-(1-chloro-cyclopropane-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-propane-2-ol is 2-20:100, preferably 5-20:100.

[0031] In this embodiment of the invention, the organic solvent is selected from at least one of halogenated hydrocarbons, ketones, and esters.

[0032] In embodiments of the present invention, halogenated hydrocarbons include, but are not limited to, substances such as chloroform, dichloromethane, dichloroethane, and 1,1,2,2-tetrachloroethane.

[0033] In this embodiment of the invention, ketones include, but are not limited to, methyl isobutyl ketone, 2-pentanone, 3-pentanone, etc. In this embodiment of the invention, esters include, but are not limited to, methyl acetate, ethyl acetate, butyl acetate, isopropyl acetate, etc.

[0034] In this embodiment of the invention, the mass ratio of the organic solvent to 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is 100:30-40, preferably 100:32-40.

[0035] In this embodiment of the invention, the mass ratio of water to 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is 15-25:30-40, preferably 18-25:32-40.

[0036] In this embodiment of the invention, the oxidation reaction temperature is 50-80℃, preferably 55-80℃.

[0037] In this embodiment of the invention, a purification step is included after the oxidation reaction.

[0038] In this embodiment of the invention, purification includes: allowing the phase to stand and separate, washing the oil phase obtained by separation with water, distilling, cooling and crystallizing, filtering, and drying.

[0039] In this embodiment of the invention, the temperature is reduced to less than or equal to 5°C.

[0040] The present invention will be described in detail below through specific examples and embodiments. It should also be understood that the following embodiments are only for specific illustration of the present invention and should not be construed as limiting the scope of protection of the present invention. Any non-essential improvements and adjustments made by those skilled in the art based on the above description of the present invention are within the scope of protection of the present invention. The specific process parameters, etc., in the following examples are merely examples within a suitable range; that is, those skilled in the art can make appropriate selections within the appropriate range based on the description herein, and are not intended to be limited to the specific values ​​in the examples below.

[0041] Example 1 like Figure 1 As shown in the figure, this embodiment provides a method for synthesizing prothioconazole, and the specific steps are as follows: S1. In a flask equipped with a mechanical stirrer and a thermometer, add 175 g of 2-(1-chloro-cyclopropane-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (0.50 mol, i.e., raw material), 500 g of dichloroethane, 7.9 g of 2,2,6,6-tetramethylpiperidine-N-oxide (0.05 mol, i.e., catalyst A), 20.5 g of ferric nitrate nonahydrate (0.05 mol, i.e., catalyst B), and 100 mL of water, and stir thoroughly to dissolve. Heat to 55°C, maintain the temperature, and introduce oxygen until the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is ≤0.5wt%, then stop the reaction. S2. Allow the mixture to stand and separate into layers. Collect the aqueous phase separately (the obtained aqueous phase can be recycled and reused). Wash the oil phase twice with 50 mL of water and distill it (the obtained mother liquor can be recycled and reused). Distill off about 400 g of dichloroethane (a large amount of solid precipitates out). Cool to 5 °C, filter, and dry to obtain 161.2 g of white powdery solid prothioconazole.

[0042] The purity of prothioconazole was tested according to GB / T 43175-2023, and the purity of prothioconazole was found to be 99.30%.

[0043] According to the formula Calculate the yield, where, The mass of prothioconazole is expressed in grams. The molar mass of prothioconazole is expressed in g / mol. The mass of the raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g; The molar mass of the starting material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g / mol. The yield was calculated to be 93.34%.

[0044] Example 2 like Figure 1 As shown in the figure, this embodiment provides a method for synthesizing prothioconazole, and the specific steps are as follows: In a flask equipped with a mechanical stirrer and a thermometer, add 175 g of 0.50 mol of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (i.e., the starting material), the aqueous phase obtained in Example 1, the mother liquor obtained after distillation and crystallization in Example 1, and 400 g of dichloroethane. Stir thoroughly to dissolve the mixture. Heat to 55°C, maintain the temperature, and introduce oxygen until the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is ≤0.5 wt%, at which point the reaction is terminated. The mixture was allowed to stand and separate into layers. The aqueous phase was collected separately, and the oil phase was washed twice with 50 mL of water and distilled to obtain approximately 350 g of dichloroethane (with a large amount of solid precipitating out). The mixture was then cooled to 4 °C, filtered, and dried to obtain 165.2 g of white powdery solid prothioconazole.

[0045] The purity of prothioconazole was tested according to GB / T 43175-2023, and the purity of prothioconazole was found to be 99.10%.

[0046] According to the formula Calculate the yield, where, The mass of prothioconazole is expressed in grams. The molar mass of prothioconazole is expressed in g / mol. The mass of the raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g; The molar mass of the starting material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g / mol. The yield was calculated to be 95.40%.

[0047] Example 3 like Figure 1 As shown in the figure, this embodiment provides a method for synthesizing prothioconazole, and the specific steps are as follows: Add 175g to a flask equipped with a mechanical stirrer and a thermometer. 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (0.50 mol, i.e., starting material), 500 g dichloroethane, 7.9 g 2,2,6,6-tetramethylpiperidine-N-oxide (0.05 mol, i.e., catalyst A), 20.5 g ferric nitrate nonahydrate (0.05 mol, i.e., catalyst B) and 100 mL water were stirred thoroughly to dissolve; the mixture was heated to 80 °C, kept at this temperature, and oxygen was introduced until the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol was ≤0.5 wt%, at which point the reaction was terminated; The mixture was allowed to stand and separate into layers. The aqueous phase was collected separately, and the oil phase was washed twice with 50 mL of water and distilled to distill off about 400 g of dichloroethane (with a large amount of solid precipitating out). The mixture was cooled to 4 °C, filtered, and dried to obtain 164.7 g of white powdery solid prothioconazole.

[0048] The purity of prothioconazole was tested according to GB / T 43175-2023, and the purity of prothioconazole was found to be 99.08%.

[0049] According to the formula Calculate the yield, where, The mass of prothioconazole is expressed in grams. The molar mass of prothioconazole is expressed in g / mol. The mass of the raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g; The molar mass of the starting material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g / mol. The yield was calculated to be 95.15%.

[0050] Example 4 like Figure 1 As shown in the figure, this embodiment provides a method for synthesizing prothioconazole, and the specific steps are as follows: Add 175g to a flask equipped with a mechanical stirrer and a thermometer. 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (0.50 mol, i.e., starting material), 500 g dichloroethane, 7.9 g 2,2,6,6-tetramethylpiperidine-N-oxide (0.05 mol, i.e., catalyst A), 20.5 g ferric nitrate nonahydrate (0.05 mol, i.e., catalyst B) and 100 mL water were stirred thoroughly to dissolve; the mixture was heated to 65 °C, kept at this temperature, and oxygen was introduced until the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol was ≤0.5 wt%, at which point the reaction was terminated; The mixture was allowed to stand and separate into layers. The aqueous phase was collected separately, and the oil phase was washed twice with 50 mL of water and distilled to distill off about 400 g of dichloroethane (with a large amount of solid precipitating out). The mixture was cooled to 4 °C, filtered, and dried to obtain 162.8 g of white powdery solid prothioconazole.

[0051] The purity of prothioconazole was tested according to GB / T 43175-2023, and the purity of prothioconazole was found to be 99.14%.

[0052] According to the formula Calculate the yield, where, The mass of prothioconazole is expressed in grams. The molar mass of prothioconazole is expressed in g / mol. The mass of the raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g; The molar mass of the starting material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g / mol. The yield was calculated to be 94.11%.

[0053] Example 5 like Figure 1 As shown in the figure, this embodiment provides a method for synthesizing prothioconazole, and the specific steps are as follows: In a flask equipped with a mechanical stirrer and a thermometer, add 175 g of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (0.50 mol, i.e., the starting material), 500 g of methyl isobutyl ketone, 7.9 g of 2,2,6,6-tetramethylpiperidine-N-oxide (0.05 mol, i.e., catalyst A), 20.5 g of ferric nitrate nonahydrate (0.05 mol, i.e., catalyst B), and 100 mL of water, and stir thoroughly to dissolve; heat to 55 °C. The mixture was kept at a constant temperature and oxygen was introduced until the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol was ≤0.5wt%, at which point the reaction was terminated. The mixture was allowed to stand and separate into layers. The aqueous phase was collected separately, and the oil phase was washed twice with 50 mL of water and distilled to obtain approximately 400 g of methyl isobutyl ketone (with a large amount of solid precipitating out). The mixture was cooled to 4 °C, filtered, and dried to obtain 161.5 g of white powdery solid prothioconazole.

[0054] The purity of prothioconazole was tested according to GB / T 43175-2023, and the purity of prothioconazole was found to be 99.30%.

[0055] According to the formula Calculate the yield, where, The mass of prothioconazole is expressed in grams. The molar mass of prothioconazole is expressed in g / mol. The mass of the raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g; The molar mass of the starting material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g / mol. The yield was calculated to be 93.51%.

[0056] Example 6 like Figure 1 As shown in the figure, this embodiment provides a method for synthesizing prothioconazole, and the specific steps are as follows: In a flask equipped with a mechanical stirrer and a thermometer, add 175 g of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (0.50 mol, i.e., the raw material), 500 g of n-butyl acetate, 7.9 g of 2,2,6,6-tetramethylpiperidine-N-oxide (0.05 mol, i.e., catalyst A), 20.5 g of ferric nitrate nonahydrate (0.05 mol, i.e., catalyst B), and 100 mL of water, and stir thoroughly to dissolve; heat to 55 °C. The mixture was kept at a constant temperature and oxygen was introduced until the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol was ≤0.5wt%, at which point the reaction was terminated. The mixture was allowed to stand and separate into layers. The aqueous phase was collected separately, and the oil phase was washed twice with 50 mL of water and distilled to distill off approximately 400 g of n-butyl acetate (with a large amount of solid precipitating out). The mixture was cooled to 4 °C, filtered, and dried to obtain 161.0 g of white powdery solid prothioconazole.

[0057] The purity of prothioconazole was tested according to GB / T 43175-2023, and the purity of prothioconazole was found to be 99.00%.

[0058] According to the formula Calculate the yield, where, The mass of prothioconazole is expressed in grams. The molar mass of prothioconazole is expressed in g / mol. The mass of the raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g; The molar mass of the starting material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g / mol. The yield was calculated to be 92.94%.

[0059] Example 7 like Figure 1 As shown in the figure, this embodiment provides a method for synthesizing prothioconazole, and the specific steps are as follows: In a flask equipped with a mechanical stirrer and a thermometer, add 175 g of 0.50 mol of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (i.e., the raw material), 500 g of n-butyl acetate, 8.65 g of 0.05 mol of 4-hydroxy-2,2,6,6-tetramethylpiperidine-N-oxide (i.e., catalyst A), 20.5 g of ferric nitrate nonahydrate (i.e., catalyst B), and 100 mL of water, and stir thoroughly to dissolve; heat to 5°C. The mixture was kept at 5°C with oxygen introduced until the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol was ≤0.5wt%, at which point the reaction was terminated. The mixture was allowed to stand and separate into layers. The aqueous phase was collected separately, and the oil phase was washed twice with 50 mL of water and distilled to distill off approximately 400 g of n-butyl acetate (with a large amount of solid precipitating out). The mixture was then cooled to 4°C, filtered, and dried to obtain 164.1 g of white powdery solid prothioconazole.

[0060] The purity of prothioconazole was tested according to GB / T 43175-2023, and the purity of prothioconazole was found to be 99.01%.

[0061] According to the formula Calculate the yield, where, The mass of prothioconazole is expressed in grams. The molar mass of prothioconazole is expressed in g / mol. The mass of the raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g; The molar mass of the starting material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g / mol. The yield was calculated to be 94.73%.

[0062] Example 8 like Figure 1 As shown in the figure, this embodiment provides a method for synthesizing prothioconazole, and the specific steps are as follows: In a flask equipped with a mechanical stirrer and a thermometer, add 175 g of 0.50 mol of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (i.e., the raw material), 500 g of n-butyl acetate, 8.2 g of 0.05 mol of N-hydroxyphthalimide (i.e., catalyst A), 20.5 g of ferric nitrate nonahydrate (i.e., catalyst B), and 100 mL of water, and stir thoroughly to dissolve. Heat to 55 °C, maintain the temperature, and circulate air. Oxygen was introduced until the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol was ≤0.5wt%, at which point the reaction was stopped. The mixture was allowed to stand and separate into layers. The aqueous phase was collected separately, and the oil phase was washed twice with 50 mL of water and distilled to distill off about 400 g of n-butyl acetate (with a large amount of solid precipitating out). The mixture was cooled to 4 °C, filtered, and dried to obtain 163.8 g of white powdery solid prothioconazole.

[0063] The purity of prothioconazole was tested according to GB / T 43175-2023, and the purity of prothioconazole was found to be 99.26%.

[0064] According to the formula Calculate the yield, where, The mass of prothioconazole is expressed in grams. The molar mass of prothioconazole is expressed in g / mol. The mass of the raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g; The molar mass of the starting material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g / mol. The yield was calculated to be 94.80%.

[0065] Example 9 like Figure 1 As shown in the figure, this embodiment provides a method for synthesizing prothioconazole, and the specific steps are as follows: In a flask equipped with a mechanical stirrer and a thermometer, add 175 g of 0.50 mol of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (i.e., the raw material), 500 g of n-butyl acetate, 10.6 g of 0.05 mol of N-acetoxyphthalimide (i.e., catalyst A), 20.5 g of ferric nitrate nonahydrate (i.e., catalyst B), and 100 mL of water, and stir thoroughly to dissolve. Heat to 55 °C and maintain the temperature. Oxygen was introduced until the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol was ≤0.5wt%, at which point the reaction was stopped. The mixture was allowed to stand and separate into layers. The aqueous phase was collected separately, and the oil phase was washed twice with 50 mL of water and distilled to distill off about 400 g of n-butyl acetate (with a large amount of solid precipitating out). The mixture was cooled to 4 °C, filtered, and dried to obtain 165.0 g of white powdery solid prothioconazole.

[0066] The purity of prothioconazole was tested according to GB / T 43175-2023, and the purity of prothioconazole was found to be 99.22%.

[0067] According to the formula Calculate the yield, where, The mass of prothioconazole is expressed in grams. The molar mass of prothioconazole is expressed in g / mol. The mass of the raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g; The molar mass of the starting material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g / mol. The yield was calculated to be 95.46%.

[0068] Example 10 like Figure 1 As shown in the figure, this embodiment provides a method for synthesizing prothioconazole, and the specific steps are as follows: In a flask equipped with a mechanical stirrer and a thermometer, add 175 g of 0.50 mol of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (i.e., the raw material), 500 g of n-butyl acetate, 8.2 g of 0.05 mol of N-hydroxyphthalimide (i.e., catalyst A), 1.25 g of cobalt acetate tetrahydrate (i.e., catalyst B), and 100 mL of water, and stir thoroughly to dissolve. Heat to 55 °C, maintain the temperature, and circulate air. Oxygen was introduced until the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol was ≤0.5wt%, at which point the reaction was stopped. The mixture was allowed to stand and separate into layers. The aqueous phase was collected separately, and the oil phase was washed twice with 50 mL of water and distilled to distill off about 400 g of n-butyl acetate (with a large amount of solid precipitating out). The mixture was cooled to 4 °C, filtered, and dried to obtain 166.1 g of white powdery solid prothioconazole.

[0069] The purity of prothioconazole was tested according to GB / T 43175-2023, and the purity of prothioconazole was found to be 99.29%.

[0070] According to the formula Calculate the yield, where, The mass of prothioconazole is expressed in grams. The molar mass of prothioconazole is expressed in g / mol. The mass of the raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g; The molar mass of the starting material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g / mol. The yield was calculated to be 96.16%.

[0071] Example 11 like Figure 1 As shown in the figure, this embodiment provides a method for synthesizing prothioconazole, and the specific steps are as follows: In a flask equipped with a mechanical stirrer and a thermometer, add 175 g of 0.50 mol of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (i.e., the raw material), 500 g of n-butyl acetate, 8.2 g of 0.05 mol of N-hydroxyphthalimide (i.e., catalyst A), 1.23 g of 0.005 mol of manganese acetate tetrahydrate (i.e., catalyst B), and 100 mL of water, and stir thoroughly to dissolve. Heat to 55 °C, maintain the temperature, and circulate air. Oxygen was introduced until the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol was ≤0.5wt%, at which point the reaction was stopped. The mixture was allowed to stand and separate into layers. The aqueous phase was collected separately, and the oil phase was washed twice with 50 mL of water and distilled to distill off about 400 g of n-butyl acetate (with a large amount of solid precipitating out). The mixture was cooled to 4 °C, filtered, and dried to obtain 165.8 g of white powdery solid prothioconazole.

[0072] The purity of prothioconazole was tested according to GB / T 43175-2023, and the purity of prothioconazole was found to be 99.35%.

[0073] According to the formula Calculate the yield, where, The mass of prothioconazole is expressed in grams. The molar mass of prothioconazole is expressed in g / mol. The mass of the raw material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g; The molar mass of the starting material 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol is expressed in g / mol. The yield was calculated to be 96.05%.

[0074] Comparative Example 1 Prothioconazole was synthesized in the same manner as in Example 1, except for the following conditions: In a flask equipped with a mechanical stirrer and a thermometer, add 175 g of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (0.50 mol, i.e., the raw material), 500 g of dichloroethane, 15.8 g of 2,2,6,6-tetramethylpiperidine-N-oxide (0.10 mol, i.e., catalyst A) and 100 mL of water, and stir thoroughly to dissolve. The mixture was heated to 55°C, kept at that temperature, and oxygen was introduced. After 24 hours of reaction, the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol was 97.55 wt%, at which point the reaction was terminated.

[0075] In this comparative example, 2,2,6,6-tetramethylpiperidine-N-oxide (0.10 mol, i.e., catalyst A) was used as the catalyst to replace the composite catalyst composed of 2,2,6,6-tetramethylpiperidine-N-oxide (catalyst A) and ferric nitrate nonahydrate (catalyst B) in a molar ratio of 1:1 in Example 1, and the reaction basically did not proceed.

[0076] Comparative Example 2 Prothioconazole was synthesized in the same manner as in Example 1, except for the following conditions: In a flask equipped with a mechanical stirrer and a thermometer, add 175 g of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol (0.50 mol, i.e., the raw material), 500 g of dichloroethane, 41.0 g of ferric nitrate nonahydrate (0.05 mol, i.e., catalyst B), and 100 mL of water, and stir thoroughly to dissolve. The mixture was heated to 55°C, kept at that temperature, and oxygen was introduced. After 24 hours of reaction, the mass percentage of 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol was 78.8 wt%, at which point the reaction was terminated.

[0077] In this comparative example, ferric nitrate nonahydrate (catalyst B) was used as the catalyst to replace the composite catalyst composed of 2,2,6,6-tetramethylpiperidine-N-oxide (catalyst A) and ferric nitrate nonahydrate (catalyst B) in a molar ratio of 1:1 in Example 1. This resulted in a slower reaction rate and lower feed conversion rate.

[0078] As can be seen from the results of Example 2, the composite catalyst in this invention can be reused.

[0079] The results from Comparative Examples 1, 2, and 1 show that the yield of Example 1 is significantly improved compared to Comparative Examples 1 and 2. This result indicates that in this invention, the combination of a nitroxide radical compound or a compound capable of generating nitroxide radicals in situ during the reaction with a transition metal catalyst demonstrates that the unpaired electrons in the molecular structure of the nitroxide radical compound or the compound capable of generating nitroxide radicals in situ during the reaction possess inherent radical characteristics and can participate in radical reactions. The transition metal catalyst intervenes in the radical reaction through mechanisms such as transition metal valence state changes and ligand dissociation, forming a cycle and thus improving the yield.

[0080] The above embodiments are merely illustrative of the principles and effects of the present invention and are not intended to limit the invention. Any person skilled in the art can modify or alter the above embodiments without departing from the spirit and scope of the present invention. Therefore, all equivalent modifications or alterations made by those skilled in the art without departing from the spirit and technical concept disclosed in the present invention should still be covered by the claims of the present invention.

Claims

1. A method for synthesizing prothioconazole, characterized in that, Prothioconazole was prepared by oxidation reaction using 2-(1-chloro-cycloprop-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-prop-2-ol as a raw material and oxygen as an oxidant in the presence of a composite catalyst, an organic solvent, and water. The composite catalyst included nitroxide free radical compounds or compounds that could generate nitroxide free radicals in situ during the reaction, and transition metal catalysts.

2. The method for synthesizing prothioconazole as described in claim 1, characterized in that, The nitroxide radical compound or the compound that can generate nitroxide radicals in situ during the reaction is selected from at least one of 2,2,6,6-tetramethylpiperidine oxide, 4-hydroxy-2,2,6,6-tetramethylpiperidine oxide, N-hydroxyphthalimide, and N-acetoxyphthalimide.

3. The method for synthesizing prothioconazole as described in claim 1, characterized in that, The transition metal catalyst is selected from at least one of iron salt catalysts, cobalt salt catalysts, and manganese salt catalysts.

4. The method for synthesizing prothioconazole as described in claim 1, characterized in that, The molar ratio of the nitroxide radical compound or the compound that can generate nitroxide radicals in situ during the reaction to the transition metal catalyst is 1-20:

1.

5. The method for synthesizing prothioconazole as described in claim 1, characterized in that, The molar ratio of the composite catalyst to the 2-(1-chloro-cyclopropane-1-yl)-1-(2-chloro-phenyl)-3-(4,5-dihydro-1,2,4-triazolidine-5-thiocarbonyl-1-yl)-propane-2-ol is 2-20:

100.

6. The method for synthesizing prothioconazole as described in claim 1, characterized in that, The organic solvent is selected from at least one of halogenated hydrocarbons, ketones, and esters.

7. The method for synthesizing prothioconazole as described in claim 1, characterized in that, The oxidation reaction is carried out at a temperature of 50-80℃.

8. The method for synthesizing prothioconazole as described in claim 1, characterized in that, The oxidation reaction is followed by a purification step.

9. The method for synthesizing prothioconazole as described in claim 8, characterized in that, The purification process includes: allowing the phase to stand and separate, washing the resulting oil phase with water, distilling, cooling and crystallizing, filtering, and drying.

10. The method for synthesizing prothioconazole as described in claim 9, characterized in that, Cool down to less than or equal to 5°C.

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