Method for synthesizing propiconazole through ionic liquid catalysis solvent-free method

Abstract

The invention relates to the technical field of propiconazole synthesis, in particular to a method for synthesizing propiconazole by an ionic liquid catalysis solvent-free method, which comprises the following steps: S1, mixing sodium 1, 2, 4-triazole or potassium 1, 2, 4-triazole and an organic alcohol solvent with 1-4 carbon atoms at room temperature, adding quaternary ammonium salt, refluxing for 10 hours, and filtering to remove insoluble substances; and distilling to remove the organic alcohol solvent with 1-4 carbon atoms to obtain the transparent and colorless 1, 2, 4-triazole-quaternary ammonium ionic liquid. And S2, mixing the 2-(2, 4-dichlorophenyl)-2-bromomethyl-4-propyl-1, 3-dioxolane with the 1, 2, 4-triazole-quaternary ammonium ionic liquid, heating to 150 to 160 DEG C, reacting for 10 to 15 hours, cooling, and carrying out post-treatment, so as to obtain propiconazole with the purity of 98 percent or more. The produced impurities are reduced, the purity and the yield of the propiconazole active compound are improved, the post-treatment is simple, the waste water is extremely little, and the method is a valuable industrial popularization and application method.

Description

Technical Field

[0001] The present invention relates to the technical field of propiconazole synthesis, and specifically to a method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method. Background Art

[0002] 1,2,4-triazole fungicides are a class of fungicides synthesized by N-alkylation at the 1-position of the 1,2,4-triazole molecular structure. They have a broad bactericidal spectrum and certain plant growth regulatory activities, including propiconazole, tebuconazole, fluconazole, triadimenol, triadimefon, bofluthrin, etc. So far, tens of thousands of triazole fungicides with good bactericidal and plant growth regulatory effects have been synthesized. Among them, propiconazole is a very important 1,2,4-triazole fungicide, and there have been many studies on its synthesis process route. Sun Yumei et al. from Shandong Institute of Pesticide Industry summarized its public process in more detail, including using 2,4-dichloroacetophenone as a raw material, first cyclizing, then brominating, and then performing N-alkylation reaction with 1,2,4-triazole to obtain the technical material, first brominating, then cyclizing, and then performing N-alkylation reaction with 1,2,4-triazole to obtain the technical material, and first brominating, then performing N-alkylation reaction with 1,2,4-triazole, and then obtaining the technical material through cyclization reaction. The mainstream process route for producing propiconazole is represented by the following equation: 。

[0004] Research shows that the effect of the last step (represented by "N-1 step") reaction directly determines the purity and yield of propiconazole technical material. US4079062, US4160838, US4391813, etc. disclose the synthesis process of propiconazole technical material and fungicide technical materials with similar structures in the N-1 step. First, 1,2,4-triazole is converted into sodium salt, and then reacted with bromide to obtain crude propiconazole technical material, and then through processes such as nitric acid salting and liquid alkali alkalization, propiconazole technical material is obtained with a yield of about 45%. It can be represented by the following equation: 。

[0006] Bu Yulan and Weng Jianquan [Fine Chemical Intermediates, 2007, 37(1), 25-27], Wang Shan [Applied Chemical Industry, 2009, 38(4), 517-519], etc. synthesized propiconazole using a similar route. Among them, the N-1 step synthesis is to react bromide with sodium salt of 1,2,4-triazole in DMSO medium and reflux for 16 hours, and after post-treatment, crude propiconazole is obtained, and then through 60% nitric acid salting and liquid alkali alkalization, light yellow propiconazole crude oil with a content of 95.0% and a yield of 81-83.0% is obtained.

[0007] Although the above method can successfully prepare propiconazole, there are the following deficiencies: (1) The content of the primary product (crude product) of propiconazole crude oil is very low. A complex process of nitrate salting and liquid alkali alkalization purification is required to increase the content to 95%, and it still fails to meet the market requirement for the content of propiconazole technical material (above 98%); (2) The complex post-treatment process results in a low actual yield of propiconazole. Although some papers report a yield of 80%, repeated experiments demonstrate that the yield of propiconazole obtained according to the methods in the papers is lower than 50%; (3) The processes of nitrate salting and liquid alkali alkalization purification will inevitably produce a large amount of industrial wastewater with high ammonia nitrogen, high COD, and high salt, and this kind of salt is nitrate with explosion hazards.

[0008] Therefore, in view of the problems raised in the above background art, those skilled in the art propose a method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method. Summary of the Invention

[0009] The purpose of the present invention is to provide a method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method to solve the problems raised in the above background art.

[0010] To achieve the above purpose, the present invention provides the following technical solutions: A method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method, comprising the following steps: S1. At room temperature, mix sodium 1,2,4-triazole or potassium 1,2,4-triazole with an organic alcohol solvent having 1-4 carbon atoms, add a quaternary ammonium salt, reflux for 10 hours, and filter to remove insoluble substances; distill off the organic alcohol solvent having 1-4 carbon atoms to obtain a transparent and colorless 1,2,4-triazole-quaternary ammonium ionic liquid; S2. Mix 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane with the 1,2,4-triazole-quaternary ammonium ionic liquid, heat up to 150-160 °C, react for 10-15 hours, cool down, and perform post-treatment to obtain propiconazole with a purity of over 98%.

[0011] Further, the molar ratio between sodium 1,2,4-triazole or potassium 1,2,4-triazole and the quaternary ammonium salt in step S1 is 1:1; the mass ratio between the organic alcohol solvent having 1-4 carbon atoms and sodium 1,2,4-triazole or potassium 1,2,4-triazole is (5-7):1.

[0012] Further, the molar ratio between the 1,2,4-triazole-quaternary ammonium ionic liquid and 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane in step S2 is (1-5):1.

[0013] Further, the quaternary ammonium salt in step S1 includes but is not limited to one of tetrabutylammonium bromide, benzyltriethylammonium chloride, choline chloride, and choline bromide.

[0014] Further, the insoluble matter in step S1 is one of sodium chloride, sodium bromide, potassium chloride, and potassium bromide.

[0015] Further, the post-treatment method in step S2 is one of vacuum distillation and solvent extraction.

[0016] Further, the pressure condition of the vacuum distillation is -0.095 MPa to -0.1 MPa, and the temperature condition is 180 - 190 °C.

[0017] Further, the organic solvent used for the solvent extraction is one of dichloromethane, dichloroethane, and chlorobenzene; the amount of the organic solvent used is 3 times the mass of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane.

[0018] Compared with the prior art, the beneficial effects of the present invention are as follows: 1. The present invention discloses a method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method. First, 1,2,4-triazole-sodium (or potassium) salt reacts with a quaternary ammonium salt to synthesize 1,2,4-triazole-quaternary ammonium ionic liquid, and the reaction ends with its reaction with 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane. After simple post-treatment, propiconazole technical with a content of more than 98% and a yield of more than 90% can be obtained. 2. In the method disclosed by the present invention, the preparation of 1,2,4-triazole-quaternary ammonium ionic liquid is simple. It is both a reaction raw material and can be used as a reaction medium without the need to add other solvents additionally. The quality and yield of the obtained propiconazole technical are better than those of the current methods; the quaternary ammonium salt first participates in the synthesis of the intermediate and then is released from the synthesis of the final product, without loss of the number of molecules, so it can be reused repeatedly in the system; at the same time, there is no need to add inorganic strong base during the reaction process, effectively avoiding the isomerization of 1,2,4-triazole to 1,3,4-triazole, and then reacting with 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane, resulting in a reduction of impurities and an increase in the purity and yield of propiconazole technical; the post-treatment is simple and the waste water is extremely small; it is a method worthy of industrialization and popularization. BRIEF DESCRIPTION OF THE DRAWINGS

[0019] Figure 1 It is the process flow chart for synthesizing propiconazole of the present invention; Figure 2This is the representative infrared spectrum detection spectrogram of 1,2,4-triazole-choline ionic liquid prepared in Example 1 of the present invention (the representative spectrograms of the 1,2,4-triazole-choline ionic liquids prepared in Examples 2 and 3 are the same as that of Example 1); Figure 3 This is the hydrogen spectrum of 1,2,4-triazole-choline ionic liquid prepared in Example 1 of the present invention (the hydrogen spectra of the 1,2,4-triazole-choline ionic liquids prepared in Examples 2 and 3 are the same as that of Example 1); Figure 4 This is the hydrogen spectrum of 1,2,4-triazole-benzyltriethylammonium ionic liquid prepared in Example 4 of the present invention; Figure 5 This is the hydrogen spectrum of 1,2,4-triazole-tetrabutylammonium ionic liquid prepared in Example 5 of the present invention; Figure 6 This is the hydrogen spectrum of propiconazole synthesized in Example 9 of the present invention (the propiconazoles prepared in Examples 6 - 8 and 10 - 13 have the same hydrogen spectrum as that of Example 9); Figure 7 This is the synthetic route diagram of the present invention. Detailed implementation manners

[0020] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative efforts shall fall within the protection scope of the present invention.

[0021] Please refer to Figures 1 to 7 , the present invention provides a technical solution: Examples 1 - 5 Preparation of 1,2,4-triazole-quaternary ammonium ionic liquid: Under room temperature conditions, sodium 1,2,4-triazole or sodium potassium 1,2,4-triazole is mixed with an organic alcohol solvent with 1 - 4 carbon atoms, a quaternary ammonium salt is added, and reflux is carried out for 10 hours. The insoluble substances are removed by filtration; the organic alcohol solvent is removed by distillation to obtain a transparent and colorless 1,2,4-triazole-quaternary ammonium ionic liquid; The quaternary ammonium salt includes but is not limited to one of tetrabutylammonium bromide, benzyltriethylammonium chloride, choline chloride, and choline bromide; The 1,2,4-triazole-quaternary ammonium ionic liquid is prepared in the following five ways, as shown in Table 1 below:

[0022] Example 6 Mix 7.08 kg of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane with 17.2 kg of 1,2,4-triazole-choline ionic liquid prepared in Example 1, heat up to 150 °C, react for 10 hours, and then cool down to room temperature; Connect an oil pump and perform vacuum distillation at -0.095 MPa to -0.1 MPa. Collect the fraction with a boiling range of 180 - 190 °C to obtain 6.36 kg of propiconazole with a purity of 98.7%, and the yield is 91.8%. The distillation residue is a small amount of propiconazole, excessive 1,2,4-triazole-choline ionic liquid, and newly formed choline bromide.

[0023] Example 7 Mix 7.08 kg of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane with 12.42 kg of 1,2,4-triazole-benzyltriethylammonium ionic liquid prepared in Example 4, heat up to 160 °C, react for 13 hours, and then cool down to room temperature; Adopt the same vacuum distillation method as in Example 6 to obtain 6.25 kg of propiconazole with a purity of 98.6%, and the yield is 90.1%. The distillation residue is a small amount of propiconazole, excessive 1,2,4-triazole-benzyltriethylammonium ionic liquid, and newly formed benzyltriethylammonium bromide.

[0024] Example 8 Mix 7.08 kg of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane with 12.42 kg of 1,2,4-triazole-benzyltriethylammonium ionic liquid prepared in Example 4, add 15 kg of DMSO, heat up to 160 °C, react for 13 hours, and then cool down to room temperature; Adopt the same vacuum distillation method as in Example 6 to obtain 5.85 kg of propiconazole with a purity of 98.3%, and the yield is 84.1%. The pre-distillation fraction is a mixture of DMSO and a small amount of propiconazole, and the distillation residue is a small amount of propiconazole, excessive 1,2,4-triazole-benzyltriethylammonium ionic liquid, and newly formed benzyltriethylammonium bromide; This example shows that adding an organic solvent does not affect the content of propiconazole, but the yield will be slightly affected, which may be due to the failure to recycle the pre-distillation fraction.

[0025] Example 9 Mix 7.08 kg of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane with 3.44 kg of 1,2,4-triazole-choline ionic liquid prepared in Example 2, heat up to 160 °C, react for 15 hours, and then cool down to room temperature; 21.24 kg of dichloromethane was added to the reaction system, and the insoluble choline bromide was removed by filtration. After the dichloromethane layer was stripped of dichloromethane, 6.55 kg of propiconazole with a content of 97.5% was obtained, and the yield was 93.3%.

[0026] Example 10 7.08 kg of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane was mixed with 12.42 kg of 1,2,4-triazole-benzyltriethylammonium ionic liquid prepared in Example 4, and the temperature was raised to 160 °C. After reacting for 13 hours, the temperature was lowered to room temperature; 21.24 kg of dichloroethane was added to the reaction system, and the insoluble benzyltriethylammonium bromide and the excess 1,2,4-triazole-benzyltriethylammonium ionic liquid were removed by liquid separation. After the dichloroethane layer was stripped of dichloroethane, 6.56 kg of propiconazole with a content of 97.4% was obtained, and the yield was 93.4%.

[0027] Example 11 7.08 kg of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane was mixed with 15.62 kg of 1,2,4-triazole-tetrabutylammonium ionic liquid prepared in Example 5, and the temperature was raised to 160 °C. After reacting for 13 hours, the temperature was lowered to room temperature; 21.24 kg of chlorobenzene was added to the reaction system, and the insoluble tetrabutylammonium bromide and the excess 1,2,4-triazole-tetrabutylammonium ionic liquid were removed by liquid separation. After the chlorobenzene layer was stripped of chlorobenzene, 6.44 kg of propiconazole with a content of 97.8% was obtained, and the yield was 92.1%.

[0028] Example 12 7.08 kg of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane was mixed with the distillation residue in the preparation process of Example 2, and the temperature was raised to 150 °C. After reacting for 10 hours, the temperature was lowered to room temperature; An oil pump was connected, and vacuum distillation was carried out at -0.095 MPa to -0.1 MPa. The fraction at 180-190 °C was taken to obtain 6.36 kg of propiconazole with a purity of 98.4%, and the yield was 91.5%. Among them, the distillation residue was a small amount of propiconazole, the excess 1,2,4-triazole-choline ionic liquid, and the newly generated choline bromide.

[0029] Example 13 7.08 kg of 2-(2,4-dichlorophenyl)-2-chloromethyl-4-propyl-1,3-dioxolane was mixed with 17.2 kg of 1,2,4-triazole-choline ionic liquid prepared in Example 3, and the temperature was raised to 150 °C. After reacting for 10 hours, the temperature was lowered to room temperature; Connect the oil pump and perform vacuum distillation at -0.095 MPa to -0.1 MPa. Take the fraction at 180 - 190 °C to obtain 1.12 kg of propiconazole with a purity of 98.3% and a yield of 16.1%. The other fractions are 2-(2,4-dichlorophenyl)-2-chloromethyl-4-propyl-1,3-dioxolane that did not participate in the reaction, a small amount of propiconazole, the excessive 1,2,4-triazole-choline ionic liquid, and newly formed choline chloride.

[0030] The present invention Figure 7 is the synthetic route diagram of the present invention (wherein X is one of chlorine and bromine, M is one of potassium and sodium, and R1, R2, R3, R4 are alkyl groups or aryl groups with 1 - 7 carbon atoms, and R1, R2, R3, R4 can be the same or different). In the figure, it is a complete reaction cycle. Specifically, sodium 1,2,4-triazole or potassium 1,2,4-triazole is added to an organic alcohol solvent with 1 - 4 carbon atoms, and then a quaternary ammonium salt is added. An ion exchange reaction occurs between the quaternary ammonium salt and sodium 1,2,4-triazole or potassium 1,2,4-triazole. The halogen in the quaternary ammonium salt combines with the potassium ion or sodium ion in sodium 1,2,4-triazole or potassium 1,2,4-triazole to form sodium chloride, potassium chloride, sodium bromide, or potassium bromide, which precipitates out from the entire solution system to form a precipitate. The precipitate is removed by filtration, and 1,2,4-triazole combines with the quaternary ammonium salt from which the halogen has been removed to form 1,2,4-triazole-quaternary ammonium ionic liquid, which exists in the organic alcohol solvent with 1 - 4 carbon atoms. The organic alcohol solvent with 1 - 4 carbon atoms is removed by distillation to obtain 1,2,4-triazole-quaternary ammonium ionic liquid; The 1,2,4-triazole-quaternary ammonium ionic liquid undergoes a substitution reaction with the added 2-(2,4-dichlorophenyl)-2-halomethyl-4-propyl-1,3-dioxolane. Among them, 1,2,4-triazole in the 1,2,4-triazole-quaternary ammonium ionic liquid substitutes the halogen in 2-(2,4-dichlorophenyl)-2-halomethyl-4-propyl-1,3-dioxolane to form the target product of the present invention, i.e., propiconazole. The remaining quaternary ammonium ion in the 1,2,4-triazole-quaternary ammonium ion combines with the removed halogen to form the initially added quaternary ammonium salt, which can be used for a new cycle reaction. The target product propiconazole in the reaction system is purified by distillation; In addition, the quaternary ammonium salt that can be recycled in the present invention may change according to the reactants during the reaction. For specific reference, see Example 7. The quaternary ammonium salt participating in the synthesis of 1,2,4-triazole-quaternary ammonium ionic liquid in Example 7 is benzyltriethylammonium chloride. During the reaction of benzyltriethylammonium chloride with sodium 1,2,4-triazole or potassium 1,2,4-triazole, the chlorine element contained in benzyltriethylammonium chloride will combine with sodium or potassium and precipitate out in the solution system, and 1,2,4-triazole-benzyltriethylammonium is synthesized. 1,2,4-triazole-benzyltriethylammonium undergoes a substitution reaction with 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane. After the benzyltriethylammonium combines with the bromine element in 2-(2,4-dichlorophenyl)-2-halomethyl-4-propyl-1,3-dioxolane, it will become benzyltriethylammonium bromide, and benzyltriethylammonium bromide will participate in the subsequent synthesis reaction as a new quaternary ammonium salt; If 2-(2,4-dichlorophenyl)-2-chloromethyl-4-propyl-1,3-dioxolane is used in the above reaction, the resulting substitution product is still benzyltriethylammonium chloride; From the above description, it can be seen that the halogen element in the quaternary ammonium salt participating in the new cycle in the present invention changes according to the type of halomethyl in 2-(2,4-dichlorophenyl)-2-halomethyl-4-propyl-1,3-dioxolane.

[0031] Although the embodiments of the present invention have been shown and described, it will be understood by those of ordinary skill in the art that various changes, modifications, substitutions, and variations can be made to these embodiments without departing from the principles and spirit of the present invention, and the scope of the present invention is defined by the appended claims and their equivalents.

Claims

1. A method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method, characterized in that, It includes the following steps: S1. Under room temperature conditions, mix sodium 1,2,4-triazole or potassium 1,2,4-triazole with an organic alcohol solvent having 1 - 4 carbon atoms, add a quaternary ammonium salt, reflux for 10 hours, and filter to remove insoluble substances; distill off the organic alcohol solvent having 1 - 4 carbon atoms to obtain a transparent and colorless 1,2,4-triazole - quaternary ammonium ionic liquid; S2. Mix 2-(2,4-dichlorophenyl)-2-(bromomethyl)-4-propyl-1,3-dioxolane with the 1,2,4-triazole - quaternary ammonium ionic liquid, heat up to 150 - 160 °C, react for 10 - 15 hours, cool down, and perform post-treatment to obtain propiconazole with a purity of over 98%.

2. The method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method according to claim 1, wherein In step S1, the molar ratio between sodium 1,2,4-triazole or potassium 1,2,4-triazole and the quaternary ammonium salt is 1:1; the mass ratio of the organic alcohol solvent having 1 - 4 carbon atoms to sodium 1,2,4-triazole or potassium 1,2,4-triazole is (5 - 7):

1.

3. A method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method according to claim 1, characterized in that, In step S2, the molar ratio of the 1,2,4-triazole - quaternary ammonium ionic liquid to 2-(2,4-dichlorophenyl)-2-(bromomethyl)-4-propyl-1,3-dioxolane is (1 - 5):

1.

4. The method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method according to claim 1, characterized in that, The quaternary ammonium salt in step S1 includes but is not limited to one of tetrabutylammonium bromide, benzyltriethylammonium chloride, choline chloride, and choline bromide.

5. A method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method according to claim 1, characterized in that, The post-treatment method in step S2 is one of vacuum distillation and solvent extraction.

6. The method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method according to claim 5, characterized in that, The pressure condition for the vacuum distillation is -0.095 MPa - -0.1 MPa, and the temperature condition is 180 - 190 °C.

7. A method for synthesizing propiconazole by an ionic liquid-catalyzed solvent-free method according to claim 5, characterized in that, The organic solvent used for the solvent extraction is one of dichloromethane, dichloroethane, and chlorobenzene; the amount of the organic solvent used is 3 times the mass of 2-(2,4-dichlorophenyl)-2-(bromomethyl)-4-propyl-1,3-dioxolane.

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