A green and efficient synthesis method of tebuconazole

Abstract

This invention discloses a green and efficient synthesis method for tebuconazole, comprising the following steps: Step 1, preparing raw materials; Step 2, reacting the raw materials; Step 3, allowing the mixture to stand and separate phases; Step 4, cooling; Step 5, obtaining the tebuconazole product; In Step 1, the ionic liquid is selected from any one or more combinations of the following: imidazole ionic liquids, pyridine ionic liquids, pyrrolidine ionic liquids, morpholine ionic liquids, and piperidine ionic liquids; In Step 2, the weight of the ionic liquid is 0.1-2 times the weight of the pentylene oxide; In Step 2, the holding temperature is 80-110℃, and the holding time is 1-5h; Compared with existing tebuconazole preparation methods, this invention has simpler reaction conditions, and can directly synthesize high-yield, high-purity tebuconazole without the need for other solvents and bases, and without the need for additional base catalysts and phase transfer catalysts. The process is greener, reduces environmental pressure, and is suitable for industrial-scale production.

Description

Technical Field

[0001] The invention relates to the technical field of fungicides, and in particular to a green and efficient synthesis method of tebuconazole. Background Art

[0002] Tebuconazole was developed by Bayer in Germany in 1986 as a highly effective, broad-spectrum, low-toxic triazole fungicide. It is widely used around the world and has the functions of protection, treatment, and eradication. Tebuconazole is mainly used as a seed treatment agent and foliar spray to prevent and control a variety of fungal diseases in crops such as wheat, rice, peanuts, vegetables, bananas, and apples. It can effectively prevent and control diseases caused by Powdery Mildew, Puccinia, Pyralidium, and Septoria, such as powdery mildew, root rot, smut, and various rusts in cereals. Tebuconazole has huge economic and social benefits, and it is very necessary to develop, produce, and optimize its synthesis process.

[0003] At present, the synthesis methods reported in the literature all use pentacyclic oxide and 1,2,4-triazole as raw materials to synthesize tebuconazole. Huang Xinhui et al. reported "Synthesis of a New Fungicide Tebuconazole" (Anhui Agricultural Science, 2007, 35 (1), 144-192) disclosed a method for synthesizing tebuconazole, which uses cyclohexanol as a solvent, heats to 150°C and keeps warm for 20 hours, and the yield of tebuconazole is 53.8%. Gao Renjun reported "Synthesis of Tebuconazole and Its Control Effect on Wheat Sharp Spot" (Master's thesis of China Agricultural University, 2002), which reported that n-butanol was used as a solvent, potassium hydroxide was used as a catalyst, and the temperature was kept at 133°C for 4 hours, and the yield of tebuconazole was 79%. Zhang Zhixing et al. reported "Study on the Synthesis of the Fungicide Tebuconazole" (Pesticide Science and Management, 2004, 2 5(5), 23-25), under the conditions of certain solvent, catalyst and potassium carbonate, CO2 gas is slowly introduced, reflux reaction, and the yield of tebuconazole is about 83%; in these synthesis methods, inorganic base and solvent are added, the yield and content of tebuconazole are low, and further optimization and improvement are needed; for example, in the synthesis method reported in Chinese patent CN109705048, in the solvent diethylene glycol monomethyl ether, pentacyclic oxide and 1,2,4-triazole are heated and kept warm in the inorganic base potassium hydroxide, and tebuconazole is obtained after post-treatment, with a yield of about 91%-92%; the yield is greatly improved, and solvent and inorganic base are added in the process, but there is still a lot of room for improvement in raw material cost and process green environmental protection; therefore, it is urgent to seek an economical, environmentally friendly, green and efficient method for synthesizing tebuconazole. Summary of the invention

[0004] The object of the present invention is to provide a green and efficient synthesis method of tebuconazole to solve the problems raised in the above background technology.

[0005] To achieve the above object, the present invention provides the following technical scheme: a green and efficient synthesis method of tebuconazole, comprising the following steps: step 1, preparing raw materials; step 2, reacting the raw materials; step 3, standing for phase separation; step 4, cooling; step 5, obtaining a tebuconazole finished product;

[0006] In the above step 1, an appropriate amount of 1,2,4-triazole, ionic liquid and pentacyclic oxide are prepared;

[0007] In the above step 2, 1,2,4-triazole and ionic liquid are added to a reaction bottle, heated to a certain temperature, and pentylene oxide is added dropwise, and the reaction is carried out by keeping the temperature after the addition is completed;

[0008] In the above step 3, after the reaction in step 2 is completed, the phases are allowed to stand and separate to obtain an ionic liquid phase and a tebuconazole phase;

[0009] In the above step 4, the ionic liquid phase obtained after phase separation in step 3 is recovered and reused, and the tebuconazole phase is cooled to room temperature to obtain a solid;

[0010] In the above step 5, the solid obtained by cooling in step 4 is slurried with a certain proportion of methanol water, and the solid is filtered and dried to obtain the finished product of tebuconazole, and the methanol water can be applied to the next batch.

[0011] Preferably, in step 1, the ionic liquid is selected from any one or more of the following combinations: imidazole ionic liquids, pyridine ionic liquids, pyrrolidine ionic liquids, morpholine ionic liquids and piperidine ionic liquids.

[0012] Preferably, in step 2, the weight of the ionic liquid is 0.1-2 times the weight of the pentylene oxide.

[0013] Preferably, in step 2, the insulation temperature is 80-110° C. and the insulation time is 1-5 h.

[0014] Preferably, in step five, the ratio of methanol to water is 30%-60%.

[0015] Preferably, in the step 5, the yield of the tebuconazole product is 93.0-93.3% and the purity is 98.0-98.3%.

[0016] Compared with the prior art, the beneficial effects of the present invention are as follows: compared with the existing method for preparing tebuconazole, the reaction conditions of the present invention are simpler, and high-yield and high-purity tebuconazole can be directly synthesized without the need for other solvents and bases, and no additional base catalyst and phase transfer catalyst are required. The process is greener, the environmental pressure is reduced, and the method is suitable for industrial scale-up production. BRIEF DESCRIPTION OF THE DRAWINGS

[0017] Figure 1The tebuconazole synthesis route of the present invention is as follows;

[0018] Figure 2 The present invention is a flow chart of the method. DETAILED DESCRIPTION

[0019] The following will be combined with the drawings in the embodiments of the present invention to clearly and completely describe the technical solutions in the embodiments of the present invention. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of the present invention.

[0020] See also Figure 1-2 , a technical solution provided by the present invention:

[0021] Example 1

[0022] A green and efficient synthesis method of tebuconazole comprises the following steps: step 1, preparing raw materials; step 2, reacting the raw materials; step 3, standing for phase separation; step 4, cooling; step 5, obtaining a tebuconazole finished product;

[0023] In the above step 1, appropriate amounts of 1,2,4-triazole, imidazole ionic liquid 1-butyl-3-methylimidazolium bromide and pentacyclic oxide are prepared;

[0024] In the above step 2, 16.7 g of 1,2,4-triazole and 50.0 g of imidazole ionic liquid 1-butyl-3-methylimidazolium bromide were added to a three-necked flask, heated and controlled at a temperature of 100-105° C., 50.0 g (0.2 mol) of pentacyclic oxide was added dropwise, and the mixture was stirred for 2-3 hours after the addition was completed;

[0025] In the above step 3, after the reaction in step 2 is completed, the phases are allowed to stand and separate to obtain an ionic liquid phase and a tebuconazole phase;

[0026] In the above step 4, the ionic liquid phase obtained after phase separation in step 3 is recovered and reused, and the tebuconazole phase is cooled to room temperature to obtain a solid;

[0027] In the above step 5, the solid obtained by cooling in step 4 is slurried with 50.0 g of 50% methanol water, and the solid is filtered and dried to obtain the finished product of tebuconazole, and the methanol water can be applied to the next batch; LCMS: 308 (M+H); 1H NMR (CDCl3) 8.22 (s, 1H), 8.03 (s, 1H), 7.21 (d, J = 8.0Hz, 2H), 6.95 (d, J = 8.0Hz, 2 H), 4.37 (s, 2H), 3.07 (s, 1H), 2.42-2.48 (m, 1H), 1.67-1.86 (m, 3H), 1.03 (s, 9H).

[0028] Example 2

[0029] A green and efficient synthesis method of tebuconazole comprises the following steps: step 1, preparing raw materials; step 2, reacting the raw materials; step 3, standing for phase separation; step 4, cooling; step 5, obtaining a tebuconazole finished product;

[0030] In the above step 1, appropriate amounts of 1,2,4-triazole, imidazole ionic liquid 1-butyl-3-methylimidazolium bromide and pentacyclic oxide are prepared; wherein the imidazole ionic liquid 1-butyl-3-methylimidazolium bromide is recovered in Example 1;

[0031] In the above step 2, 16.7 g of 1,2,4-triazole and 50.0 g of imidazole ionic liquid 1-butyl-3-methylimidazolium bromide were added to a three-necked flask, heated and controlled at a temperature of 100-105° C., 50.0 g (0.2 mol) of pentacyclic oxide was added dropwise, and the mixture was stirred for 2-3 hours after the addition was completed;

[0032] In the above step 3, after the reaction in step 2 is completed, the phases are allowed to stand and separate to obtain an ionic liquid phase and a tebuconazole phase;

[0033] In the above step 4, the ionic liquid phase obtained after phase separation in step 3 is recovered and reused, and the tebuconazole phase is cooled to room temperature to obtain a solid;

[0034] In the above step 5, the solid obtained by cooling in step 4 is slurried with 50.0 g of 50% methanol water, and the solid is filtered and dried to obtain the finished tebuconazole, and the methanol water can be applied to the next batch.

[0035] Example 3

[0036] A green and efficient synthesis method of tebuconazole comprises the following steps: step 1, preparing raw materials; step 2, reacting the raw materials; step 3, standing for phase separation; step 4, cooling; step 5, obtaining a tebuconazole finished product;

[0037] In the above step 1, appropriate amounts of 1,2,4-triazole, imidazole ionic liquid 1-benzyl-3-methylimidazolium chloride and pentacyclic oxide are prepared;

[0038] In the above step 2, 16.7 g of 1,2,4-triazole and 50.0 g of imidazole ionic liquid 1-benzyl-3-methylimidazolium chloride are added to a three-necked flask, heated and the temperature is controlled at 100-105° C., 50.0 g (0.2 mol) of pentacyclic oxide is added dropwise, and the mixture is stirred for 2-3 hours after the addition is completed;

[0039] In the above step 3, after the reaction in step 2 is completed, the phases are allowed to stand and separate to obtain an ionic liquid phase and a tebuconazole phase;

[0040] In the above step 4, the ionic liquid phase obtained after phase separation in step 3 is recovered and reused, and the tebuconazole phase is cooled to room temperature to obtain a solid;

[0041] In the above step 5, the solid obtained by cooling in step 4 is slurried with 50.0 g of 50% methanol water, and the solid is filtered and dried to obtain the finished tebuconazole, and the methanol water can be applied to the next batch.

[0042] Example 4

[0043] A green and efficient synthesis method of tebuconazole comprises the following steps: step 1, preparing raw materials; step 2, reacting the raw materials; step 3, standing for phase separation; step 4, cooling; step 5, obtaining a tebuconazole finished product;

[0044] In the above step 1, appropriate amounts of 1,2,4-triazole, imidazole ionic liquid 1-benzyl-3-methylimidazolium chloride and pentacyclic oxide are prepared; wherein the imidazole ionic liquid 1-benzyl-3-methylimidazolium chloride is recovered in Example 3;

[0045] In the above step 2, 16.7 g of 1,2,4-triazole and 50.0 g of imidazole ionic liquid 1-benzyl-3-methylimidazolium chloride are added to a three-necked flask, heated and the temperature is controlled at 100-105° C., 50.0 g (0.2 mol) of pentacyclic oxide is added dropwise, and the mixture is stirred for 2-3 hours after the addition is completed;

[0046] In the above step 3, after the reaction in step 2 is completed, the phases are allowed to stand and separate to obtain an ionic liquid phase and a tebuconazole phase;

[0047] In the above step 4, the ionic liquid phase obtained after phase separation in step 3 is recovered and reused, and the tebuconazole phase is cooled to room temperature to obtain a solid;

[0048] In the above step 5, the solid obtained by cooling in step 4 is slurried with 50.0 g of 50% methanol water, and the solid is filtered and dried to obtain the finished tebuconazole, and the methanol water can be applied to the next batch.

[0049] The properties of the above embodiments are compared in the following table:

[0050]

[0051]

[0052] Based on the above, the advantage of the present invention is that the invention uses pentamethylene oxide and 1,2,4-triazole, an intermediate of pentamethylene oxide, as raw materials to directly synthesize pentamethylene oxide without the need for other solvents and bases, and the yield and purity of the obtained pentamethylene oxide are high. In addition, the method is green and environmentally friendly, and the process is simple and efficient, and has great industrial development value.

[0053] It will be apparent to those skilled in the art that the invention is not limited to the details of the exemplary embodiments described above and that the invention can be implemented in other specific forms without departing from the spirit or essential features of the invention. Therefore, the embodiments should be considered exemplary and non-limiting in all respects, and the scope of the invention is defined by the appended claims rather than the foregoing description, and it is intended that all variations falling within the meaning and scope of the equivalent elements of the claims be included in the invention. Any reference numeral in a claim should not be considered as limiting the claim to which it relates.

Claims

1. A green synthesis method of tebuconazole, comprising the following steps: Step 1, preparing raw materials; step 2, reacting the raw materials; step 3, standing for phase separation; step 4, cooling; step 5, obtaining the finished tebuconazole; characterized in that: ； In the above step 1, an appropriate amount of 1,2,4-triazole, ionic liquid and pentacyclic oxide are prepared; In the above step 2, 1,2,4-triazole and ionic liquid are added to a reaction bottle, heated to a certain temperature, and pentacyclic oxide is added dropwise, and the reaction is carried out by keeping the temperature after the addition is completed; In the above step 3, after the reaction in step 2 is completed, the phases are allowed to stand and separate to obtain an ionic liquid phase and a tebuconazole phase; In the above step 4, the ionic liquid phase obtained after phase separation in step 3 is recovered and reused, and the tebuconazole phase is cooled to room temperature to obtain a solid; In the above step 5, the solid obtained by cooling in step 4 is slurried with a certain proportion of methanol water, and the solid is filtered and dried to obtain the finished tebuconazole, and the methanol water can be applied to the next batch; In the step 1, the ionic liquid is selected from imidazole ionic liquids; In the step 2, the weight of the ionic liquid is 0.1-2 times the weight of the pentylene oxide.

2. A green synthesis method of tebuconazole according to claim 1, characterized in that: In the step 2, the insulation temperature is 80-110° C. and the insulation time is 1-5 hours.

3. A green synthesis method of tebuconazole according to claim 1, characterized in that: In the step 5, the ratio of methanol to water is 30%-60%.

4. A green synthesis method of tebuconazole according to claim 1, characterized in that: In the step 5, the yield of the tebuconazole finished product is 93.0-93.3%, and the purity is 98.0-98.3%.

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