Synthetic method and application of epoxiconazole intermediate

Abstract

The invention discloses an epoxiconazole intermediate synthesis method and application, and the epoxiconazole intermediate synthesis method comprises the following steps: adding 55-65 g of 1-chloro-3-(2-chlorphenyl)-2-(4-fluorophenyl)-2-propanol, 130-140 g of toluene and 5 g of ethylene glycol into a reaction flask, uniformly mixing, then dropwise adding concentrated sulfuric acid at 20-30 DEG C, then dropwise adding acetic anhydride, reacting for 1-2 hours, then adding a catalyst, and reacting for 1-2 hours at the temperature of 20-30 DEG C to obtain the epoxiconazole intermediate. The preparation method comprises the following steps: adding toluene into a reaction kettle, carrying out a thermal insulation reaction at 20-30 DEG C, dropwise adding water after the reaction is completed, stirring for layering, adding water into a toluene layer, washing to be neutral, carrying out reduced pressure concentration on the toluene layer until the toluene layer is dry to obtain an intermediate product, adding the intermediate product into methanol, dissolving, cooling, crystallizing, filtering and drying. According to the method, 1-chloro-3-(2-chlorphenyl)-2-(4-fluorophenyl)-2-propanol is adopted as a raw material, a small amount of ethidene diamine and concentrated sulfuric acid are adopted as catalysts, acetic anhydride is adopted as a dehydrating agent, water in molecules can be well removed under the low-temperature condition, 80% or above of target Z-configuration target products can be obtained, and the method is suitable for industrial production.

Description

Technical Field

[0001] The invention relates to the field of preparation of epoxiconazole intermediates, in particular to a synthesis method and application of an epoxiconazole intermediate. Background Art

[0002] In order to meet the needs of agricultural production, agricultural producers will use some fungicides to spray on crops, and triazole fungicides are one of them. Fluoxepiconazole is a commonly used triazole fungicide, which can inhibit the synthesis of ergosterol in pathogens, hinder the formation of bacterial cell walls, and increase the activity of chitinase in crops, causing the contraction of fungal haustoria and inhibiting the invasion of pathogens. It mainly has preventive and therapeutic effects on Basidiomycetes and Deuteromycetes on wheat, barley, rice, sugar beets, and rapeseed.

[0003] Many raw materials are used in the synthesis of fluopicolide. Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene is the key intermediate for the synthesis of fluopicolide. However, when synthesizing Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene in the existing method, the reaction temperature is high, resulting in high energy consumption, long reaction cycle and many by-products. People are in urgent need of improving the synthesis method of Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene. Summary of the invention

[0004] The object of the present invention is to provide a method for synthesizing an epoxiconazole intermediate to solve the problems raised in the above background technology.

[0005] To achieve the above object, the present invention provides the following technical solutions:

[0006] A method for synthesizing an epoxiconazole intermediate comprises the following specific steps: adding 55-65g of 1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propanol, 130-140g of toluene and 5g of ethylene glycol into a reaction bottle and mixing them evenly; then dripping concentrated sulfuric acid at 20-30 degrees Celsius; then dripping acetic anhydride after the dripping of concentrated sulfuric acid is completed; then carrying out heat preservation reaction at 20-30 degrees Celsius after the dripping of acetic anhydride is completed; then dripping water after the reaction is complete and stirring to separate layers; then adding water to the toluene layer to wash until it is neutral; then concentrating the toluene layer under reduced pressure to dryness to obtain an intermediate product; and then adding the intermediate product into methanol to dissolve, cool, crystallize, filter and dry to obtain Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene, wherein Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene is the target product.

[0007] As a further solution of the present invention: the mass of concentrated sulfuric acid added dropwise is 4 g.

[0008] As a further solution of the present invention: the mass of acetic anhydride added dropwise is 33 g.

[0009] As a further solution of the present invention: the insulation reaction time is 50-70 minutes.

[0010] As a further solution of the present invention: the mass of the water added dropwise is 40 g, and the temperature when the water is added dropwise is 20-30 degrees Celsius.

[0011] As a further solution of the present invention: industrial grade methanol is used as methanol, the mass of methanol is 90 g, and the temperature of the reduced pressure concentrated toluene layer is 70-80 degrees Celsius.

[0012] The invention is also used to protect the use of the epoxiconazole intermediate obtained by the above synthesis method in the synthesis of epoxiconazole.

[0013] Compared with the prior art, the invention has the following beneficial effects: the invention adopts 1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propanol as a raw material, adopts a small amount of ethylenediamine and concentrated sulfuric acid as a catalyst, and adopts acetic anhydride as a dehydrating agent, so that water in the molecule can be well removed under low temperature conditions, and more than 80% of the target Z-configuration target product can be obtained; the raw materials and auxiliary materials of the invention are cheap and easy to purchase, the preparation method is simple and has high safety, the reaction temperature and energy consumption are low, the production cost is reduced, the reaction cycle is short, the by-products are small, the green environmental protection is high, and the invention is suitable for industrial production. DETAILED DESCRIPTION

[0014] The technical solution of this patent is further described in detail below in conjunction with specific implementation methods.

[0015] The invention uses 1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propanol as a starting material, uses a small amount of ethylenediamine and concentrated sulfuric acid as a catalyst, and reacts with acetic anhydride to achieve dehydration, thereby obtaining a target product Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene with less by-products. The synthesis method of the invention can well remove water from molecules under low temperature conditions, and can obtain more than 80% of the target Z configuration target product. Compared with the existing Martin dehydration, the requirement for the moisture content of the environmental reagent is not high, and the rearrangement to obtain the target configuration can be well controlled.

[0016] Example 1

[0017] A method for synthesizing an epoxiconazole intermediate comprises the following specific steps: adding 55 g of 1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propanol, 130 g of toluene and 5 g of ethylene glycol to a reaction bottle and mixing them evenly, then dripping 4 g of concentrated sulfuric acid at 20 degrees Celsius, dripping 33 g of acetic anhydride after the dripping of concentrated sulfuric acid is completed, and carrying out a heat preservation reaction at 20 degrees Celsius for 50 minutes after the dripping of acetic anhydride is completed, sampling and testing to ensure that the reaction is complete, then controlling the temperature to 20 degrees Celsius, dripping 40 g of water and stirring to separate layers, and then adding 40 g of water to the toluene layer. Add an appropriate amount of water to wash until neutral, concentrate the toluene layer under reduced pressure at 70 degrees Celsius to dryness to obtain an intermediate product, add the intermediate product into 90g of industrial grade methanol to dissolve, cool, crystallize, filter and dry to obtain Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene. Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene is the target product with a purity of 96.4% and a yield of 48.6%.

[0018] Example 2

[0019] A method for synthesizing an epoxiconazole intermediate comprises the following specific steps: adding 58 g of 1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propanol, 134 g of toluene and 5 g of ethylene glycol to a reaction bottle and mixing them evenly, then dripping 4 g of concentrated sulfuric acid at 24 degrees Celsius, dripping 33 g of acetic anhydride after the dripping of concentrated sulfuric acid is completed, and carrying out a heat preservation reaction at 24 degrees Celsius for 57 minutes after the dripping of acetic anhydride is completed, sampling and testing to ensure that the reaction is complete, then controlling the temperature to 22 degrees Celsius, dripping 40 g of water and stirring to separate layers, and then adding 40 g of water to the toluene layer. Add an appropriate amount of water to wash until neutral, concentrate the toluene layer under reduced pressure at 74 degrees Celsius to dryness to obtain an intermediate product, add the intermediate product into 90g of industrial grade methanol to dissolve, cool, crystallize, filter and dry to obtain Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene. Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene is the target product with a purity of 93.4% and a yield of 47.7%.

[0020] Example 3

[0021] A method for synthesizing an epoxiconazole intermediate comprises the following specific steps: adding 60 g of 1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propanol, 140 g of toluene and 5 g of ethylene glycol into a reaction bottle and mixing them evenly, then dripping 4 g of concentrated sulfuric acid at 25 degrees Celsius, dripping 33 g of acetic anhydride after the dripping of concentrated sulfuric acid is completed, and carrying out heat preservation reaction at 26 degrees Celsius for 60 minutes after the dripping of acetic anhydride is completed, sampling and testing to ensure that the reaction is complete, then controlling the temperature to 26 degrees Celsius, dripping 40 g of water and stirring to separate layers, and then adding the toluene layer to the reaction mixture. An appropriate amount of water is added to the reaction mixture, and the mixture is washed until it becomes neutral. The toluene layer is concentrated under reduced pressure at 75 degrees Celsius to dryness to obtain an intermediate product. The intermediate product is added to 90 g of industrial grade methanol to dissolve, cool, crystallize, filter and dry to obtain Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene. Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene is the target product with a purity of 98.5% and a yield of 53%.

[0022] Example 4

[0023] A method for synthesizing an epoxiconazole intermediate comprises the following specific steps: adding 63 g of 1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propanol, 146 g of toluene and 5 g of ethylene glycol to a reaction bottle and mixing them evenly, then dripping 4 g of concentrated sulfuric acid at 28 degrees Celsius, dripping 33 g of acetic anhydride after the dripping of concentrated sulfuric acid is completed, and carrying out a heat preservation reaction at 29 degrees Celsius for 65 minutes after the dripping of acetic anhydride is completed, sampling and testing to ensure that the reaction is complete, then controlling the temperature to 28 degrees Celsius, dripping 40 g of water and stirring to separate layers, and then adding 40 g of water to the toluene layer. Add an appropriate amount of water to wash until neutral, concentrate the toluene layer under reduced pressure at 77 degrees Celsius to dryness to obtain an intermediate product, add the intermediate product into 90g of industrial grade methanol to dissolve, cool, crystallize, filter and dry to obtain Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene. Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene is the target product with a purity of 94.9% and a yield of 50.7%.

[0024] Example 5

[0025] A method for synthesizing an epoxiconazole intermediate comprises the following specific steps: adding 65 g of 1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propanol, 150 g of toluene and 5 g of ethylene glycol to a reaction bottle and mixing them evenly, then dripping 4 g of concentrated sulfuric acid at 30 degrees Celsius, dripping 33 g of acetic anhydride after the dripping of concentrated sulfuric acid is completed, and carrying out a heat preservation reaction at 30 degrees Celsius for 70 minutes after the dripping of acetic anhydride is completed, sampling and testing to ensure that the reaction is complete, then controlling the temperature to 30 degrees Celsius, dripping 40 g of water and stirring to separate layers, and then adding the toluene layer to the reaction mixture; Add an appropriate amount of water to wash until neutral, concentrate the toluene layer under reduced pressure at 80 degrees Celsius to dryness to obtain an intermediate product, add the intermediate product into 90g of industrial grade methanol to dissolve, cool, crystallize, filter and dry to obtain Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene. Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene is the target product with a purity of 97.1% and a yield of 49.2%.

[0026] It can be seen from the above examples that the Z-1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propylene obtained by the preparation method of the present invention has a minimum purity of 93.4%, which is higher than that of the existing reaction system and has broad application prospects.

[0027] It will be apparent to those skilled in the art that the present invention is not limited to the details of the exemplary embodiments described above and that the present invention can be implemented in other specific forms without departing from the spirit or essential features of the present invention. Therefore, the embodiments should be considered exemplary and non-restrictive in all respects, and the scope of the present invention is defined by the appended claims rather than the above description, and it is intended that all changes falling within the meaning and scope of the equivalent elements of the claims be included in the present invention.

[0028] In addition, it should be understood that although the present specification is described according to implementation modes, not every implementation mode contains only one independent technical solution. This description of the specification is only for the sake of clarity. Those skilled in the art should regard the specification as a whole. The technical solutions in each embodiment may also be appropriately combined to form other implementation modes that can be understood by those skilled in the art.

Claims

1. A method for synthesizing an epoxiconazole intermediate, characterized in that: The specific steps are as follows: 55-65g of 1-chloro-3-(2-chlorophenyl)-2-(4-fluorophenyl)-2-propanol, 130-140g of toluene and 5g of ethylene glycol are added into a reaction bottle and mixed evenly, then concentrated sulfuric acid is added dropwise at 20-30 degrees Celsius, acetic anhydride is added dropwise after the addition of concentrated sulfuric acid is completed, and the reaction is carried out at 20-30 degrees Celsius after the addition of acetic anhydride is completed. After the reaction is complete, water is added dropwise and stirred to separate layers, water is added to the toluene layer to wash until it is neutral, and the toluene layer is concentrated under reduced pressure to dryness to obtain an intermediate product, and the intermediate product is added into methanol to dissolve, cool, crystallize, filter and dry.

2. The method for synthesizing an epoxiconazole intermediate according to claim 1, wherein: The mass of the concentrated sulfuric acid added dropwise is 4 g.

3. The method for synthesizing an epoxiconazole intermediate according to claim 1 or 2, characterized in that: The mass of the acetic anhydride added dropwise is 33 g.

4. The method for synthesizing an epoxiconazole intermediate according to claim 1, wherein: The time of the thermal insulation reaction is 50-70 minutes.

5. The method for synthesizing an epoxiconazole intermediate according to claim 1 or 2, characterized in that: The mass of the water added dropwise is 40 g, and the temperature when the water is added dropwise is 20-30 degrees Celsius.

6. The method for synthesizing an epoxiconazole intermediate according to claim 1, wherein: The methanol is industrial grade methanol, the mass of the methanol is 90 g, and the temperature of the reduced pressure concentrated toluene layer is 70-80 degrees Celsius.

7. Use of an epoxiconazole intermediate obtained by the method for synthesizing an epoxiconazole intermediate according to any one of claims 1 to 6 in synthesizing epoxiconazole.