A method for preparing tebuconazole epoxide

Abstract

The invention discloses a method for preparing an epoxide of tebuconazole, wherein the method for preparing an epoxide of tebuconazole is as follows: p-chlorobenzaldehyde and pinacolone are used as raw materials, and 4,4-dimethyl-1-(4-chlorophenyl)-1-pentene-3-one is obtained through an aldol condensation reaction, and 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone is obtained by reacting the epoxide with a hydrogen source and a Pb-Zr / Al2O3 catalyst for hydrogenation, and then 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone is obtained, and then carbonyl epoxidation is performed with n-decyl methyl sulfide, methyl bromide, etc. to obtain an epoxide of tebuconazole. The present invention adopts a hydrogen source and a Pb-Zr / Al2O3 catalyst in the hydrogenation process, avoids the use of a flammable Raney nickel catalyst and explosive hydrogen, and adopts n-decyl methyl sulfide and methyl bromide in the carbonyl epoxidation process, thereby improving the purity and yield of the product and realizing the clean production of the epoxide of tebuconazole.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for preparing an epoxide of tebuconazole. Background Art

[0002] Tebuconazole epoxide is an intermediate product in the preparation of tebuconazole, and its chemical name is 2-[2-(4-chlorophenyl)ethyl]-2-(1,1-dimethylethyl)oxirane. Tebuconazole is a triazole fungicide that can inhibit the biosynthesis of ergosterol in fungi. It is used as a seed treatment agent and foliar spray. It has a broad fungicide spectrum, high activity, and long lasting effect. It is mainly used to prevent and control various fungal diseases on crops such as wheat, peanuts, and vegetables.

[0003] The synthesis method of tebuconazole epoxide is mainly: using p-chlorobenzaldehyde as the starting material, through aldehyde-ketone condensation, catalytic hydrogenation, and carbonyl epoxidation, the tebuconazole epoxide is obtained. In the synthesis process, aldehyde-ketone condensation is used to obtain enone, and enone is catalytically hydrogenated to obtain 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone (PCBDM-3-pentanone), and PCBDM-3-pentanone is subjected to carbonyl epoxidation to obtain tebuconazole epoxide.

[0004] In the process of catalytic hydrogenation of ketene, Raney nickel catalyst is often used, but the reaction selectivity of Raney nickel catalyst is not high. In the synthesis of ketene hydrogenation, when the double bond is hydrogenated to about 80%, carbonyl hydrogenation will occur. It can be seen that the use of Raney nickel catalyst will lead to a decrease in the yield and purity of tebuconazole epoxide; and hydrogen is used as a hydrogenation reagent. Hydrogen is easy to explode and difficult to store, which is not conducive to industrial production. In the process of carbonyl epoxidation of PCBDM-3-pentanone, sulfonium salts (sulfur ylide) are often used, and sulfur ylide is synthesized from dimethyl sulfide / dimethyl sulfate and ethyl bromide / methyl iodide as raw materials. Dimethyl sulfide is a toxic substance with a foul odor, a low boiling point, easy volatility, and difficult recovery. The large-scale use of dimethyl sulfide will cause the surrounding environment to deteriorate. Dimethyl sulfate is toxic and has a great irritation to the human respiratory tract.

[0005] CN109456288A discloses a method for preparing a tebuconazole intermediate. The method comprises reacting PCBDM-3-pentanone and a long-chain sulfide in the presence of toluene and dimethyl sulfate, and then adding potassium hydroxide to continue the reaction to obtain a tebuconazole intermediate. The yield of the obtained tebuconazole intermediate is 87%-84% and the purity is 97%. However, dimethyl sulfate is still used in the synthesis process because it is volatile and toxic and can easily cause environmental pollution. In the document "Improvement of the Synthesis Process of Tebuconazole Intermediate 2-[2-(4-Fluorophenyl)ethyl]-2-(1,1-dimethylethyl)oxirane" (Zheng Qi, Du Xiaohua, Pesticides, 2016, 55(4):246-249), n-octyl methyl sulfide is used instead of dimethyl ether sulfur to synthesize sulfonium salt, and the tebuconazole epoxide is synthesized with PCBDM-3-pentanone. Although the pollution in the synthesis process is small, the yield of the tebuconazole epoxide is only 90.5%.

[0006] Therefore, a method for preparing tebuconazole epoxide is needed to improve the yield and purity of tebuconazole epoxide, while reducing the pollution of raw materials to the environment, so as to realize the industrial large-scale clean production of tebuconazole epoxide. Summary of the invention

[0007] In view of the above prior art, the object of the present invention is to provide a method for preparing the epoxide of tebuconazole. The method adopts formic acid or isopropanol as a hydrogen source, selects a catalyst with Pb-Zr as an active center and Al2O3 as a carrier, and performs double bond hydrogenation on ketene, thereby avoiding the use of Raney nickel catalyst and hydrogen, reducing potential safety hazards in industrial production, and improving the purity and yield of the product. At the same time, n-decyl methyl sulfide and methyl bromide are used as raw materials for carbonyl epoxidation treatment, thereby avoiding pollution generated during the production process.

[0008] To achieve the above object, the present invention adopts the following technical solution:

[0009] The present invention provides a method for preparing an epoxide of tebuconazole, comprising the following steps:

[0010] (1) p-Chlorobenzaldehyde, pinacolone, methanol and sodium hydroxide are mixed and reacted to obtain 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one;

[0011] (2) Mixing 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one with a hydrogen source and a Pb-Zr / Al2O3 catalyst, and performing a hydrogenation reaction to obtain 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone;

[0012] (3) n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH are added to toluene, and the epoxide of tebuconazole is obtained after reaction and purification.

[0013] Preferably, in step (1), the material-liquid ratio of p-chlorobenzaldehyde, pinacolone, sodium hydroxide and methanol is 4 g: (3.2-3.5) g: (0.25-0.35) g: (110-130) mL.

[0014] Preferably, in step (1), the reaction temperature is 40-50° C. and the reaction time is 8-10 h.

[0015] When the temperature is lower than 40°C, the reaction rate is too slow, the reaction time is long, the labor cost is increased, and it is not conducive to industrial production. In addition, the yield of 4,4-dimethyl-1-(4-chlorophenyl)-1-pentene-3-one is low, and the conversion rate of the raw materials is low. When the temperature is higher than 50°C, although the reaction time is shortened, the production content of the two by-products, p-chlorobenzoic acid and p-chlorobenzyl alcohol, is significantly increased, which is not conducive to the purity of 4,4-dimethyl-1-(4-chlorophenyl)-1-pentene-3-one.

[0016] Preferably, in step (2), the hydrogen source is formic acid or isopropanol.

[0017] Preferably, the preparation method of the Pb-Zr / Al2O3 catalyst is: lead nitrate, zirconium nitrate and aluminum nitrate are mixed in a molar ratio of (1-3): (1-3): (8-10), dissolved in 1L of water to form a first mixed solution, the pH value is adjusted to 10-12, stirred, and the obtained precipitate is washed, dried at 120°C for 12h, ground, and calcined at 550°C for 2.5-3.5h to obtain the Pb-Zr / Al2O3 catalyst.

[0018] Preferably, in step (2), the mass ratio of 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one, formic acid or isopropanol, and Pb-Zr / Al2O3 catalyst is 1:(2-5):(0.05-1.5).

[0019] Preferably, in step (2), the hydrogenation reaction time is 80-140° C. and the reaction time is 4-8 h.

[0020] Preferably, in step (3), the molar ratio of n-decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH is (1.3-1.7):(1.3-1.7):1:(4-7).

[0021] Preferably, in step (3), the mass ratio of the total mass of n-decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone, and KOH to toluene is (0.8-1.2):1.

[0022] Preferably, in step (3), the reaction temperature is 10-30° C. and the reaction time is 2-4 h.

[0023] Preferably, in step (3), the purification method is: adding water to the solution after the reaction and stirring, separating the liquids, extracting the aqueous layer with toluene 2-3 times, combining the organic phases after the extraction, drying with anhydrous sodium sulfate, and filtering.

[0024] Beneficial effects of the present invention:

[0025] Compared with the prior art using catalytic hydrogenation and carbonyl epoxidation, the present invention uses transfer hydrogenation to convert ketene into pentanone, uses a hydrogen source with active hydrogen as a hydrogen donor to replace gaseous hydrogen, can effectively avoid the use of hydrogen, solves the problem of Raney nickel catalyst being flammable and difficult to operate, and at the same time, improves the yield and purity of 2-[(4-chlorophenylethyl)]-2-tert-butyl oxirane, which is beneficial to the yield and purity of tebuconazole epoxide. In the carbonyl epoxidation process, the present invention uses n-decyl methyl sulfide and methyl bromide as raw materials to carbonyl epoxidize 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone, which can effectively reduce the pollution generated during the reaction process. DETAILED DESCRIPTION

[0026] It should be noted that the following detailed descriptions are illustrative and are intended to provide further explanation of the present application. Unless otherwise specified, all technical and scientific terms used herein have the same meanings as those commonly understood by those skilled in the art to which the present application belongs.

[0027] As described in the background technology, the production process of the epoxide of tebuconazole is as follows: pinacolone and p-chlorobenzaldehyde are subjected to aldol condensation, double bond hydrogenation and carbonyl epoxidation to obtain 2-[(4-chlorophenethyl)]-2-tert-butyl oxirane. In the prior art, Raney nickel catalyst and hydrogen are used in the double bond hydrogenation process, but Raney nickel catalyst is flammable and hydrogen is explosive. There are great safety hazards in the process of industrial production. Dimethyl sulfide and dimethyl sulfate are used in the carbonyl epoxidation process, wherein dimethyl sulfide is volatile and dimethyl sulfate is toxic, which will pollute the environment and is not conducive to human health.

[0028] The preparation process of the epoxide of tebuconazole is:

[0029]

[0030] Based on this, the present invention proposes a method for preparing the epoxide of tebuconazole. In view of the flammable and explosive problems existing in the double bond hydrogenation process in the prior art, the present invention adopts a transfer hydrogenation method, uses formic acid or isopropanol as a hydrogen source, Pb-Zr alloy as an active center and Al2O3 as a catalyst carrier, avoids the use of flammable and explosive raw materials, is conducive to large-scale industrial production, and the use of catalysts can improve the yield and purity of 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone, which is further conducive to improving the yield and purity of tebuconazole epoxide. At the same time, in view of the toxic and easy-to-pollute problems of dimethyl sulfide and dimethyl sulfate in carbonyl epoxidation in the prior art, the present invention uses n-decyl methyl sulfide and methyl bromide as raw materials to reduce environmental pollution.

[0031] The method for preparing the epoxide of tebuconazole comprises the following steps:

[0032] (1) Add sodium hydroxide to methanol, stir and mix evenly, cool to room temperature, then add pinacolone and p-chlorobenzaldehyde, the solid-liquid ratio of p-chlorobenzaldehyde, pinacolone, sodium hydroxide and methanol is 4g: (3.2-3.5)g: (0.25-0.35)g: (110-130)mL, heat to 40-50°C and keep warm, react for 8-10h, and obtain 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one;

[0033] (2) Mix lead nitrate, zirconium nitrate and aluminum nitrate in a molar ratio of (1-3): (1-3): (8-10), dissolve in 1L of water to form a first mixed solution, add NaOH or Na2CO3 to adjust the pH to 10-12, stir to react, wash the resulting precipitate, dry it at 120°C for 12h, grind it, and calcine it at 550°C for 2.5-3.5h to obtain a Pb-Zr / Al2O3 catalyst;

[0034] Mix 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one, formic acid or isopropanol, and Pb-Zr / Al2O3 catalyst in a mass ratio of 1:(2-5):(0.05-1.5), and perform hydrogenation reaction at 80-140°C for 4-8h to obtain 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone;

[0035] (3) n-decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH are added to toluene. The molar ratio of n-decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH is (1.3-1.7):(1.3-1.7):1:(4-7). The mass ratio of the total mass of n-decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH to toluene is (0.8-1.2):1. The reaction is carried out at 10-30° C. for 2-4 hours. Water is added to the reaction solution and stirred. The reaction solution is allowed to stand until the liquid is separated. The aqueous layer is extracted with toluene for 2-3 times. The organic phases after the extraction are combined, dried with anhydrous sodium sulfate, and filtered to obtain the epoxide of tebuconazole.

[0036] In order to enable those skilled in the art to more clearly understand the technical solution of the present application, the technical solution of the present application will be described in detail below in conjunction with specific embodiments.

[0037] The test materials used in the examples of the present invention are all conventional test materials in the art and can be purchased through commercial channels.

[0038] Example 1: Preparation method of tebuconazole epoxide

[0039] (1) Sodium hydroxide was added to methanol, stirred and mixed evenly, and then cooled to room temperature, and then pinacolone and p-chlorobenzaldehyde were added. The solid-liquid ratio of p-chlorobenzaldehyde, pinacolone, sodium hydroxide and methanol was 4 g:3.3 g:0.3 g:120 mL. The temperature was raised to 45°C and kept warm. The reaction was carried out for 9 hours to obtain 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one;

[0040] (2) Lead nitrate, zirconium nitrate and aluminum nitrate were mixed in a molar ratio of 2:2:9, dissolved in 1L of water to form a first mixed solution, and NaOH was added to adjust the pH of the first mixed solution to 11, stirred and reacted, and the resulting precipitate was washed, dried at 120°C for 12h, ground, and calcined at 550°C for 3h to obtain a Pb-Zr / Al2O3 catalyst;

[0041] 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one, formic acid or isopropanol, and Pb-Zr / Al2O3 catalyst were mixed in a mass ratio of 1:3.5:1.0, and hydrogenated at 100°C for 6 hours to obtain 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone;

[0042] (3) n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH are added to toluene. The molar ratio of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH is 1.5:1.5:1:5.5, and the mass ratio of the total mass of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH to toluene is 1.0:1. The reaction is carried out at 20° C. for 3 h. Water is added to the reaction solution and stirred. The reaction solution is allowed to stand until the liquid is separated. The aqueous layer is extracted with toluene for 3 times. The organic phases after the extraction are combined, dried over anhydrous sodium sulfate, and filtered to obtain the epoxide of tebuconazole.

[0043] The tebuconazole epoxide obtained in this example was measured under the same gas chromatography conditions as the CAS 80443-63-6 standard sample. The retention time of the main peak of the chromatogram in this example was consistent with the main peak retention time of 2-[2-(4-chlorophenyl)ethyl]-2-(1,1-dimethylethyl)oxirane in the standard sample. It can be proved that the product obtained in this example is 2-[2-(4-chlorophenyl)ethyl]-2-(1,1-dimethylethyl)oxirane. The yield of the tebuconazole epoxide obtained in this example was 96.5%, and the purity was 99.4% as determined by liquid chromatography.

[0044] Example 2: Preparation of epoxide of tebuconazole

[0045] (1) Sodium hydroxide was added to methanol, stirred and mixed evenly, cooled to room temperature, and then pinacolone and p-chlorobenzaldehyde were added. The solid-liquid ratio of p-chlorobenzaldehyde, pinacolone, sodium hydroxide and methanol was 4 g:3.2 g:0.252 g:110 mL. The temperature was raised to 40°C and kept warm. The reaction was carried out for 10 hours to obtain 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one.

[0046] (2) Lead nitrate, zirconium nitrate and aluminum nitrate were mixed in a molar ratio of 1:1:8, dissolved in 1L of water to form a first mixed solution, and NaOH was added to adjust the pH to 10. The mixture was stirred for reaction, and the resulting precipitate was washed, dried at 120°C for 12h, ground, and calcined at 550°C for 3.5h to obtain a Pb-Zr / Al2O3 catalyst.

[0047] 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one, formic acid or isopropanol, and Pb-Zr / Al2O3 catalyst were mixed in a mass ratio of 1:2:0.05, and hydrogenated at 80°C for 8 hours to obtain 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone;

[0048] (3) n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH are added to toluene, wherein the molar ratio of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH is 1.3:1.3:1:4, and the mass ratio of the total mass of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH to toluene is 0.8:1. The reaction is carried out at 10-30° C. for 4 h. Water is added to the reaction solution and stirred. The reaction solution is allowed to stand until the liquid is separated. The aqueous layer is extracted twice with toluene, and the organic phases after the extraction are combined, dried over anhydrous sodium sulfate, and filtered to obtain the epoxide of tebuconazole.

[0049] The tebuconazole epoxide obtained in this example was measured under the same gas chromatography conditions as the CAS 80443-63-6 standard sample. The retention time of the main peak of the chromatogram in this example was consistent with the main peak retention time of 2-[2-(4-chlorophenyl)ethyl]-2-(1,1-dimethylethyl)oxirane in the standard sample. It can be proved that the product obtained in this example is 2-[2-(4-chlorophenyl)ethyl]-2-(1,1-dimethylethyl)oxirane. The yield of the tebuconazole epoxide obtained in this example was 95.8%, and the purity was 98.7% as determined by liquid chromatography.

[0050] Example 3: Preparation of epoxide of tebuconazole

[0051] (1) Sodium hydroxide was added to methanol, stirred and mixed evenly, and then cooled to room temperature, and then pinacolone and p-chlorobenzaldehyde were added. The solid-liquid ratio of p-chlorobenzaldehyde, pinacolone, sodium hydroxide and methanol was 4 g:3.5 g:0.35 g:130 mL. The temperature was raised to 50°C and kept warm. The reaction was carried out for 8 hours to obtain 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one;

[0052] (2) Lead nitrate, zirconium nitrate and aluminum nitrate were mixed in a molar ratio of 3:3:10, dissolved in 1L of water to form a first mixed solution, and Na2CO3 was added to adjust the pH to 12. The mixture was stirred for reaction, and the resulting precipitate was washed, dried at 120°C for 12h, ground, and calcined at 550°C for 3.5h to obtain a Pb-Zr / Al2O3 catalyst.

[0053] 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one, formic acid or isopropanol, and Pb-Zr / Al2O3 catalyst were mixed in a mass ratio of 1:5:1.5, and hydrogenated at 140°C for 4 hours to obtain 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone;

[0054] (3) n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH are added to toluene, wherein the molar ratio of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH is 1.7:1.7:1:7, and the mass ratio of the total mass of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH to toluene is 1.2:1. The reaction is carried out at 10-30° C. for 2 h. Water is added to the reaction solution and stirred. The reaction solution is allowed to stand until the liquid is separated. The aqueous layer is extracted twice with toluene, and the organic phases after the extraction are combined, dried over anhydrous sodium sulfate, and filtered to obtain the epoxide of tebuconazole.

[0055] The tebuconazole epoxide obtained in this example was measured under the same gas chromatography conditions as the CAS 80443-63-6 standard sample. The retention time of the main peak of the chromatogram in this example was consistent with the main peak retention time of 2-[2-(4-chlorophenyl)ethyl]-2-(1,1-dimethylethyl)oxirane in the standard sample. It can be proved that the product obtained in this example is 2-[2-(4-chlorophenyl)ethyl]-2-(1,1-dimethylethyl)oxirane. The yield of the tebuconazole epoxide obtained in this example was 94.6%, and the purity was 98.3% as determined by liquid chromatography.

[0056] Comparative Example 1:

[0057] (1) Sodium hydroxide was added to methanol, stirred and mixed evenly, and then cooled to room temperature, and then pinacolone and p-chlorobenzaldehyde were added. The solid-liquid ratio of p-chlorobenzaldehyde, pinacolone, sodium hydroxide and methanol was 4 g:3.3 g:0.3 g:120 mL. The temperature was raised to 45°C and kept warm. The reaction was carried out for 9 hours to obtain 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one;

[0058] (2) Mix lead nitrate and zirconium nitrate in a molar ratio of 2:2, dissolve in 1L of water to form a first mixed solution, add NaOH to adjust the pH of the first mixed solution to 11, stir and react, wash the resulting precipitate, dry it at 120°C for 12h, grind it, and calcine it at 550°C for 3h to obtain a Pb-Zr catalyst;

[0059] 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one, formic acid or isopropanol, and Pb-Zr catalyst were mixed in a mass ratio of 1:3.5:1.0, and hydrogenated at 100°C for 6 hours to obtain 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone;

[0060] (3) n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH were added to toluene. The molar ratio of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH was 1.5:1.5:1:5.5, and the mass ratio of the total mass of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH to toluene was 1.0:1. The reaction was carried out at 20° C. for 3 h. Water was added to the reaction solution and stirred. The reaction solution was allowed to stand until the liquid was separated. The aqueous layer was extracted with toluene for 3 times. The organic phases after the extraction were combined, dried with anhydrous sodium sulfate, and filtered to obtain the epoxide of tebuconazole.

[0061] The yield of the epoxide of tebuconazole obtained in this example was 79.6%, and the purity detected by liquid chromatography was 83.1%.

[0062] Comparative Example 2:

[0063] (1) Sodium hydroxide was added to methanol, stirred and mixed evenly, and then cooled to room temperature, and then pinacolone and p-chlorobenzaldehyde were added. The solid-liquid ratio of p-chlorobenzaldehyde, pinacolone, sodium hydroxide and methanol was 4 g:3.3 g:0.3 g:120 mL. The temperature was raised to 45°C and kept warm. The reaction was carried out for 9 hours to obtain 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one;

[0064] (2) Aluminum nitrate was mixed in a molar ratio of 2:2:9 and dissolved in 1L of water to form a first mixed solution. NaOH was added to adjust the pH of the first mixed solution to 11, and the mixture was stirred and reacted. The resulting precipitate was washed, dried at 120°C for 12h, ground, and calcined at 550°C for 3h to obtain an Al2O3 catalyst.

[0065] 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one, formic acid or isopropanol, and Al2O3 catalyst were mixed in a mass ratio of 1:3.5:1.0, and hydrogenated at 100°C for 6 hours to obtain 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone;

[0066] (3) n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH were added to toluene. The molar ratio of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH was 1.5:1.5:1:5.5, and the mass ratio of the total mass of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH to toluene was 1.0:1. The reaction was carried out at 20° C. for 3 h. Water was added to the reaction solution and stirred. The reaction solution was allowed to stand until the liquid was separated. The aqueous layer was extracted with toluene for 3 times. The organic phases after the extraction were combined, dried with anhydrous sodium sulfate, and filtered to obtain the epoxide of tebuconazole.

[0067] The yield of the epoxide of tebuconazole obtained in this example was 78.5%, and the purity detected by liquid chromatography was 81.7%.

[0068] Comparative Example 3:

[0069] (1) Sodium hydroxide was added to methanol, stirred and mixed evenly, and then cooled to room temperature, and then pinacolone and p-chlorobenzaldehyde were added. The solid-liquid ratio of p-chlorobenzaldehyde, pinacolone, sodium hydroxide and methanol was 4 g:3.3 g:0.3 g:120 mL. The temperature was raised to 45°C and kept warm. The reaction was carried out for 9 hours to obtain 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one;

[0070] (2) 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one and potassium hydroxide were mixed in a mass ratio of 3500:0.5 to obtain a mixture, and then a Raney nickel catalyst was added. The mass ratio of 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one to the Raney nickel catalyst was 1000:16. Hydrogen was introduced at 75° C. and the pressure was controlled to be 1.2 MPa. The mixture was reacted to obtain 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone;

[0071] (3) n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH were added to toluene. The molar ratio of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH was 1.5:1.5:1:5.5, and the mass ratio of the total mass of n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH to toluene was 1.0:1. The reaction was carried out at 20° C. for 3 h. Water was added to the reaction solution and stirred. The reaction solution was allowed to stand until the liquid was separated. The aqueous layer was extracted with toluene for 3 times. The organic phases after the extraction were combined, dried with anhydrous sodium sulfate, and filtered to obtain the epoxide of tebuconazole.

[0072] The yield of the epoxide of tebuconazole obtained in this example was 90.6%, and the purity detected by liquid chromatography was 92.8%.

[0073] The above description is only the preferred embodiment of the present application and is not intended to limit the present application. For those skilled in the art, the present application may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present application shall be included in the protection scope of the present application.

Claims

1. A method for preparing an epoxide of tebuconazole, characterized in that: The following steps are involved: (1) p-Chlorobenzaldehyde, pinacolone, methanol and sodium hydroxide are mixed and reacted to obtain 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one; (2) Mixing 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one with a hydrogen source and a Pb-Zr / Al2O3 catalyst, and performing a hydrogenation reaction to obtain 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone; (3) n-Decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH are added to toluene, and the epoxide of tebuconazole is obtained after reaction and purification.

2. The method for preparing the epoxide of tebuconazole according to claim 1, wherein: In step (1), the material-liquid ratio of p-chlorobenzaldehyde, pinacolone, sodium hydroxide and methanol is 4 g: (3.2-3.5) g: (0.25-0.35) g: (110-130) mL; The reaction temperature is 40-50°C and the reaction time is 8-10h.

3. The method for preparing the epoxide of tebuconazole according to claim 1, wherein: In step (2), the preparation method of the Pb-Zr / Al2O3 catalyst is as follows: lead nitrate, zirconium nitrate and aluminum nitrate are mixed in a molar ratio of (1-3): (1-3): (8-10), dissolved in 1L of water to form a first mixed solution, the pH is adjusted to 10-12, stirred, and the resulting precipitate is washed, dried at 120°C for 12h, ground, and calcined at 550°C for 2.5-3.5h to obtain the Pb-Zr / Al2O3 catalyst.

4. The method for preparing the epoxide of tebuconazole according to claim 1, wherein: In step (2), the hydrogen source is formic acid or isopropanol; The hydrogenation reaction time is 80-140°C and the reaction time is 4-8h.

5. The method for preparing the epoxide of tebuconazole according to claim 1, wherein: In step (2), the mass ratio of 4,4-dimethyl-1-(4-chlorophenyl)-1-penten-3-one, hydrogen source, and Pb-Zr / Al2O3 catalyst is 1:(2-5):(0.05-1.5).

6. The method for preparing the epoxide of tebuconazole according to claim 1, characterized in that: In step (3), the molar ratio of n-decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone and KOH is (1.3-1.7):(1.3-1.7):1:(4-7); The mass ratio of the total mass of n-decyl methyl sulfide, methyl bromide, 1-(4-chlorophenyl)-4,4-dimethyl-3-pentanone, and KOH to toluene is (0.8-1.2):

1.

7. The method for preparing the epoxide of tebuconazole according to claim 1, wherein: In step (3), the reaction temperature is 10-30°C and the reaction time is 2-4h.

8. The method for preparing the epoxide of tebuconazole according to claim 1, characterized in that: In step (3), the purification method is: adding water to the solution after the reaction and stirring, separating the liquids, extracting the aqueous layer with toluene 2-3 times, combining the organic phases after the extraction, drying with anhydrous sodium sulfate, and filtering.

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