A method for synthesizing prohexadione calcium using non-translocated impurities in the production process of prohexadione calcium

Abstract

The present invention discloses a method for synthesizing prohexadione calcium using non-translocated impurities from the production process of prohexadione calcium. The non-translocated impurities are reacted with an acid, and the resulting product is reacted with an esterifying agent in the presence of an organic base to obtain a prohexadione calcium intermediate. The method of synthesizing a prohexadione calcium intermediate using non-translocated impurities from the production process of prohexadione calcium has mild conditions, high yields, and is suitable for industrial use in treating abnormal materials.

Description

Technical Field

[0001] The invention belongs to the field of pesticide synthesis, and particularly relates to a method for resynthesizing a prohexadione calcium intermediate by utilizing impurities generated due to partial acidity in the system during esterification, thereby improving the yield of prohexadione calcium. Background Art

[0002] Prohexadione-calcium is a plant growth regulator with the structural formula shown below:

[0003]

[0004] Prohexadione calcium is a calcium salt of cyclohexanecarboxylic acid. The active ingredient is prohexadione. When sprayed on plants, it is rapidly absorbed by leaf cells. Plants synthesize gibberellins in the leaves, allowing it to act directly on its target, resulting in high activity. Prohexadione calcium also has a short half-life, no more than 24 hours in soil rich in microorganisms. Furthermore, its final metabolites are carbon dioxide and water, making it a low-toxic, residue-free, and green product.

[0005] The applicant synthesized prohexadione calcium according to the following synthetic route:

[0006]

[0007] In the third step, when the amount of propionyl chloride added was excessive (the amount of propionyl chloride added was twice that of compound 1), the system became acidic. After the reaction, no acylated intermediate 2 was obtained, but compound 3 was obtained (compound 3 was analyzed by H NMR spectrum (such as Figure 1 and Figure 2 Analysis of possible causes: When synthesizing compound 1, ethanol solution was used as solvent and sodium ethoxide was used as base. Compound 1 was not completely purified and contained sodium ethoxide / ethanol. When dichloroethane was replaced as solvent, the temperature was lowered to about 0 degrees, and triethylamine and propionyl chloride were added, due to excessive addition of propionyl chloride, the sodium ethoxide / ethanol in the system reacted with compound 1 to obtain compound 3.

[0008]

[0009] The formation of compound 3 prevents subsequent steps, such as the translocation reaction, from proceeding, resulting in a low yield of prohexadione-calcium. In the prior art, the target intermediate is typically transferred to the aqueous phase through subsequent reactions, while the impurity (compound 3) is separated in the organic phase. The organic solvent is then treated to remove the impurities and reused as a recovery solvent. Summary of the Invention

[0010] The present invention addresses the problem of impurities generated during the esterification process during prohexadione-calcium production, which can affect the yield of prohexadione-calcium. The goal is to provide a method for resynthesizing a prohexadione-calcium intermediate using impurities generated during the esterification process due to the acidic nature of the system, thereby increasing the yield of prohexadione-calcium. The present method achieves a high yield of prohexadione-calcium and is suitable for industrial production.

[0011] The technical solution adopted in the present invention is as follows:

[0012] 1) Compound 3 (an impurity that does not shift during the esterification process of prohexadione calcium) is reacted with an acid to obtain Compound 4;

[0013] 2) The obtained compound 4 reacts with an esterifying agent in the presence of an organic base to obtain compound 2,

[0014]

[0015]

[0016] In step 1) of the above method, the molar amount of the acid added is 1%-5% of the molar amount of compound 3;

[0017] The acid is one or a mixture of hydrochloric acid, methanesulfonic acid, glacial acetic acid, pickling chloride (such as ferric chloride), and ammonium cerium nitrate;

[0018] The reaction is carried out in a solvent, which can be one or a mixed solvent of water, methanol, ethanol, toluene, xylene, acetonitrile, ethyl acetate, dichloroethane, and tetrahydrofuran;

[0019] The reaction temperature may be 20-80°C, preferably 30-50°C;

[0020] The reaction time may be 2-5 hours.

[0021] The reaction time is related to the temperature. When the temperature is low, the reaction time is long. When the temperature is high, the reaction time is short, but the yield is low.

[0022] In step 2) of the above method, the organic base may be one or a mixture of diethylamine, triethylamine, pyridine, and piperidine;

[0023] The pH of the reaction system is greater than 10;

[0024] The esterifying agent can specifically be propionyl chloride;

[0025] The molar ratio of compound 4 to the esterifying agent can be: 1:1.2-1.6;

[0026] The reaction temperature may be 0-20°C, and the reaction time may be 1-3 hours.

[0027] The method of synthesizing a prohexadione calcium intermediate by utilizing non-translocated impurities in the production process of prohexadione calcium has mild conditions and high yield, and is suitable for industrial use in treating abnormal materials. BRIEF DESCRIPTION OF THE DRAWINGS

[0028] Figure 1 is the hydrogen nuclear magnetic resonance spectrum of compound 3 in the present invention.

[0029] Figure 2 is the carbon NMR spectrum of compound 3 in the present invention. DETAILED DESCRIPTION

[0030] The present invention will be further described in detail below in conjunction with specific embodiments. The examples provided are only for illustrating the present invention and are not intended to limit the scope of the present invention. The examples provided below can serve as a guide for further improvements by those skilled in the art and are not intended to limit the present invention in any way.

[0031] Unless otherwise specified, the experimental methods in the following examples are conventional methods and were performed according to the techniques or conditions described in the literature in the field or according to the product instructions. The materials and reagents used in the following examples, unless otherwise specified, were all commercially available.

[0032] In the synthesis of compound 1, an ethanol solution is used as a solvent and sodium ethoxide is used as a reaction raw material. After compound 1 is generated, the ethanol solvent is evaporated by heating. The ethanol desolventizing is not complete, and sodium ethoxide / ethanol is contained. When dichloroethane is replaced as the solvent, the temperature is lowered to below 10 degrees, triethylamine is added to adjust the acidity and alkalinity of the system, and then the esterifying agent propionyl chloride is added. Due to the active nature of propionyl chloride, the reaction is unstable. Excessive addition (molar ratio with compound 1 is 1.8-2.0:1), too high a reaction temperature (greater than 20°C) or too long a stirring time will cause the sodium ethoxide / ethanol in the system to react with compound 1 to obtain compound 3. Compound 3 cannot be normally transposed, affecting the product yield. The toluene solution of compound 3 is now collected and treated to achieve the purpose of improving the product yield.

[0033] Example 1: Preparation of prohexadione-calcium from failed translocation wastewater

[0034] 1. Take 100g of failed translocation waste liquid (containing 10g of compound), add 0.1g FeCl3 and 5g water, and stir at room temperature for 2h;

[0035] 2. After separating the water phase, add 5g of anhydrous CaCl2 to absorb water and filter to obtain the filtrate;

[0036] 3. Add 5 g of triethylamine to the filtrate to adjust the pH to weak alkalinity, and add 5.2 g of propionyl chloride dropwise to cold water (less than 20°C) to carry out esterification reaction. The addition is completed in 80 minutes (the yield of the esterified product is 70%).

[0037] 4. Add 5g of triethylamine to adjust the pH, add 2g of DMAP and carry out the transposition reaction at 100°C for 1h. The reaction is completed. The transposition material is washed with 100g of water once. After removing the aqueous phase, it is washed with 20g of 36% concentrated hydrochloric acid to remove impurities;

[0038] 5. Add 20g of 32% liquid caustic soda and 20g of primary water for alkaline hydrolysis, react at room temperature for 30min, separate the aqueous phase, adjust the pH to neutral, dissolve 10g of CaCl2 in 40g of water, carry out calcification reaction, stir for 20min, filter and dry to obtain prohexadione calcium.

[0039] Example 2: Preparation of prohexadione-calcium from failed translocation wastewater

[0040] 1. Take 100 g of the failed translocation waste liquid (containing 10 g of compound), add 0.065 g of methanesulfonic acid and 5 g of water, and stir at 80 ° C for 3 h;

[0041] 2. After separating the water phase, add 5g of anhydrous CaCl2 to absorb water and filter to obtain the filtrate;

[0042] 3. Add 20g of triethylamine to the filtrate to adjust the pH to weak alkalinity, and add 5.5g of propionyl chloride dropwise to cold water (less than 20°C) to carry out esterification reaction. The addition is completed in 80 minutes (the yield of the esterified product is 65%).

[0043] 4. Add 5g of triethylamine to adjust the pH, add 2g of DMAP and carry out the transposition reaction at 100°C for 1h. The reaction is completed. The transposition material is washed with 100g of water once. After removing the aqueous phase, it is washed with 20g of 36% concentrated hydrochloric acid to remove impurities;

[0044] 5. Add 20g of 32% liquid caustic soda and 20g of primary water for alkaline hydrolysis, react at room temperature for 30min, separate the aqueous phase, adjust the pH to neutral, dissolve 10g of CaCl2 in 40g of water, carry out calcification reaction, stir for 20min, filter and dry to obtain prohexadione calcium.

[0045] The present invention has been described in detail above. For those skilled in the art, without departing from the purpose and scope of the present invention, and without the need to carry out unnecessary experimental conditions, the present invention can be implemented in a wide range under equivalent parameters, concentrations and conditions. Although the present invention provides specific embodiments, it should be understood that further improvements can be made to the present invention. In short, according to the principles of the present invention, this application is intended to include any changes, uses or improvements to the present invention, including changes that depart from the disclosed scope in this application and are made using conventional techniques known in the art.

Claims

1. A method for resynthesizing a prohexadione calcium intermediate by utilizing impurities generated during the esterification process of prohexadione calcium, comprising the following steps: 1) Compound 3, an impurity produced during the esterification of prohexadione calcium, is reacted with FeCl3 to obtain compound 4; 2) The obtained compound 4 reacts with an esterifying agent in the presence of an organic base to obtain compound 2, 。 2. The method according to claim 1, wherein: In step 1), the molar amount of FeCl3 added is 1%-5% of the molar amount of compound 3.

3. The method according to claim 1 or 2, characterized in that: In step (1), the reaction is carried out in a solvent, The solvent is one or a mixed solvent of water, methanol, ethanol, toluene, xylene, acetonitrile, ethyl acetate, dichloroethane and tetrahydrofuran.

4. The method according to claim 1 or 2, characterized in that: In step (1), the reaction temperature is 20-80°C; the reaction time is 2-5 hours.

5. The method according to claim 1 or 2, characterized in that: In step 2), the organic base is one or a mixture of diethylamine, triethylamine, pyridine, and piperidine; The pH of the reaction system is greater than 10; The esterifying agent is propionyl chloride; The molar ratio of compound 4 to the esterifying agent is 1:1.2-1.

6.

6. The method according to claim 1 or 2, wherein: In step (2), the reaction temperature is 0-20°C and the reaction time is 1-3 h.

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