A method for synthesizing propiconazole by using ionic liquid as catalyst in solvent-free system

Abstract

The application relates to the technical field of propiconazole synthesis, in particular to a method for synthesizing propiconazole by using ionic liquid catalysis and a solvent-free method, which comprises the following steps: S1, under the condition of room temperature, 1,2,4-triazole sodium or 1,2,4-triazole potassium and 1-4 carbon atom organic alcohol solvent are mixed, a quaternary ammonium salt is added, reflux is carried out for 10 hours, and insoluble substances are removed through filtration; 1-4 carbon atom organic alcohol solvent is removed through distillation, and transparent colorless 1,2,4-triazole-quaternary ammonium ionic liquid is obtained; S2, 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane is mixed with the 1,2,4-triazole-quaternary ammonium ionic liquid, the temperature is increased to 150-160 DEG C, reaction is carried out for 10-15 hours, the temperature is decreased, post-treatment is carried out, and propiconazole with a purity of more than 98% is obtained. The method has the advantages that impurities are reduced, the purity and yield of propiconazole are improved, post-treatment is simple, and wastewater is extremely small, and is a valuable method for industrialization popularization and application.

Description

TECHNICAL FIELD

[0001] The application relates to the technical field of propiconazole synthesis, in particular to a method for synthesizing propiconazole by using ionic liquid catalysis and a solvent-free method. BACKGROUND

[0002] 1,2,4-triazole fungicides are a kind of fungicides synthesized by 1-alkylation of 1,2,4-triazole molecular structure, have a wide fungicidal spectrum and certain plant growth regulating activity, and include propiconazole, tebuconazole, fluconazole, triadimenol, triadimefon, uniconazole and the like. Up to now, people have synthesized tens of thousands of 1,2,4-triazole fungicides with good fungicidal and plant growth regulating effects. Propiconazole is a very important 1,2,4-triazole fungicide, and researches on the synthesis process route of propiconazole are also many. Sun Yumei of Shandong Pesticide Research Institute and others have summarized the public process in detail, which includes the following: taking 2,4-dichloroacetophenone as raw material, first cyclization, then bromination and then N-alkylation with 1,2,4-triazole to obtain the original drug, first bromination, then cyclization and then N-alkylation with 1,2,4-triazole to obtain the original drug, and first bromination, then N-alkylation with 1,2,4-triazole and then cyclization to obtain the original drug. The mainstream process route for producing propiconazole is represented by the following equation:

[0003]

[0004] Researches show that the effect of the last step (represented by the "N-1 step") directly determines the purity and yield of the propiconazole original drug. US4079062, US4160838 and US4391813 disclose the synthesis process of the N-1 step of the propiconazole original drug and the original drug of the fungicide with a similar structure, that is, first converting 1,2,4-triazole into a sodium salt, then reacting with a bromide to obtain a crude propiconazole original drug, and then purifying through nitric acid salification and liquid alkali alkalization to obtain the propiconazole original drug with a yield of about 45%. The equation is represented as follows:

[0005]

[0006] Bu Yulan and Weng Jianquan [Fine Chemical Intermediates, 2007, 37 (1), 25-27] and Wang Shan [Applied Chemistry, 2009, 38 (4), 517-519] adopt a similar route to synthesize propiconazole, wherein the N-1 step synthesis is through the reaction of a bromide with 1,2,4-triazole sodium salt in a DMSO medium, refluxing for 16 hours, and then post-treatment to obtain a crude propiconazole, which is then salified by 60% nitric acid and alkalized by liquid alkali to obtain a light yellow propiconazole crude oil with a content of 95.0% and a yield of 81-83.0%.

[0007] The above method can successfully prepare propiconazole, but has the following shortcomings: (1) the propiconazole crude product (crude product) has a very low content, a complex nitric acid salting and liquid alkali alkalization purification process is needed to make the content reach 95%, and the content still cannot meet the market requirement (more than 98%); (2) the complex post-treatment process leads to a low actual yield of propiconazole, although a paper gives a yield of 80%, but the reproducible experiment demonstrates that the yield of propiconazole obtained according to the method in the paper is less than 50%; (3) the nitric acid salting and liquid alkali alkalization purification process will inevitably produce a large amount of industrial wastewater with high ammonia nitrogen, high COD and high salt, and the salt is nitrate which has an explosion hazard.

[0008] Therefore, in view of the problems in the above background art, the skilled in the art proposes a method for synthesizing propiconazole by ionic liquid catalysis and solvent-free method. SUMMARY

[0009] The purpose of the present application is to provide a method for synthesizing propiconazole by ionic liquid catalysis and solvent-free method, to solve the problems in the above background art.

[0010] To achieve the above purpose, the present application provides the following technical solution:

[0011] A method for synthesizing propiconazole by ionic liquid catalysis and solvent-free method, comprising the following steps:

[0012] S1, under room temperature conditions, mix 1,2,4-triazole sodium or 1,2,4-triazole potassium and 1-4 carbon atom organic alcohol solvent, add quaternary ammonium salt, reflux for 10 hours, filter to remove insoluble matter; distill off the 1-4 carbon atom organic alcohol solvent to obtain transparent colorless 1,2,4-triazole-quaternary ammonium ionic liquid;

[0013] S2, mix 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane with 1,2,4-triazole-quaternary ammonium ionic liquid, heat to 150-160℃, react for 10-15 hours, cool down, and post-treat to obtain propiconazole with a purity of more than 98%.

[0014] Further, the molar ratio between 1,2,4-triazole sodium or 1,2,4-triazole potassium and quaternary ammonium salt in step S1 is 1:1; the mass ratio of 1-4 carbon atom organic alcohol solvent to 1,2,4-triazole sodium or 1,2,4-triazole potassium is (5-7):1.

[0015] Further, the molar ratio of 1,2,4-triazole-quaternary ammonium ionic liquid to 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane in step S2 is (1-5):1.

[0016] Further, the quaternary ammonium salt in the step S1 includes but is not limited to one of tetrabutylammonium bromide, benzyl triethyl ammonium chloride, choline chloride, choline bromide.

[0017] Further, the insoluble substance in the step S1 is one of sodium chloride, sodium bromide, potassium chloride, potassium bromide.

[0018] Further, the post-processing method in the step S2 is one of reduced pressure distillation, solvent extraction.

[0019] Further, the pressure condition of the reduced pressure distillation is -0.095MPa-0.1MPa, and the temperature condition is 180-190℃.

[0020] Further, the organic solvent used in the solvent extraction is one of dichloromethane, dichloroethane, chlorobenzene; and the amount of the organic solvent is 3 times of the mass of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane.

[0021] Compared with the prior art, the method has the beneficial effects that:

[0022] 1. The method for synthesizing propiconazole by using ionic liquid catalysis and solvent-free method is disclosed, which comprises the following steps: synthesizing 1,2,4-triazole-quaternary ammonium ionic liquid by reacting 1,2,4-triazole sodium (or potassium) salt with quaternary ammonium salt, and then reacting the 1,2,4-triazole-quaternary ammonium ionic liquid with 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane, and finally obtaining propiconazole technical material with a content of more than 98% and a yield of more than 90% by simple post-processing.

[0023] 2. In the method, the 1,2,4-triazole-quaternary ammonium ionic liquid is simple to make, and is both a reaction raw material and a reaction medium, and no other solvent needs to be additionally added, and the quality and yield of the obtained propiconazole technical material are better than those of the prior art; the quaternary ammonium salt is released from the synthesis of the final product after participating in the synthesis of the intermediate, and thus the number of molecules is not lost, and the quaternary ammonium salt can be repeatedly used in the system; meanwhile, no inorganic strong base needs to be additionally added in the reaction process, and thus the isomerization of 1,2,4-triazole into 1,3,4-triazole is effectively avoided, and then the reaction of 1,3,4-triazole with 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane is generated, impurities are reduced, the purity and yield of the propiconazole technical material are improved, the post-processing is simple, and wastewater is extremely little; and the method is a valuable method for industrialization promotion and application. BRIEF DESCRIPTION OF DRAWINGS

[0024] Figure 1 The process flow chart for synthesizing propiconazole according to the method is shown in the figure;

[0025] Figure 2Infrared spectrum of 1,2,4-triazole-choline ionic liquid prepared in Example 1 of the present application (the infrared spectrum of 1,2,4-triazole-choline ionic liquid prepared in Examples 2 and 3 is the same as that of Example 1);

[0026] Figure 3 Proton spectrum of 1,2,4-triazole-choline ionic liquid prepared in Example 1 of the present application (the proton spectrum of 1,2,4-triazole-choline ionic liquid prepared in Examples 2 and 3 is the same as that of Example 1);

[0027] Figure 4 Proton spectrum of 1,2,4-triazole-benzyltriethylammonium ionic liquid prepared in Example 4 of the present application;

[0028] Figure 5 Proton spectrum of 1,2,4-triazole-tetrabutylammonium ionic liquid prepared in Example 5 of the present application;

[0029] Figure 6 Proton spectrum of propiconazole synthesized in Example 9 of the present application (the proton spectrum of propiconazole prepared in Examples 6-8 and 10-13 is the same as that of Example 9);

[0030] Figure 7 Synthetic route map of the present application. DETAILED DESCRIPTION

[0031] The technical solutions in the embodiments of the present application will be clearly and completely described below with reference to the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, rather than all the embodiments. Based on the embodiments in the present application, all other embodiments obtained by those skilled in the art without creative labor fall within the scope of protection of the present application.

[0032] Please refer to Figures 1 to 7 The present application provides a technical solution:

[0033] Examples 1-5

[0034] Preparation of 1,2,4-triazole-quaternary ammonium ionic liquid:

[0035] Under room temperature, mix 1,2,4-triazole sodium or 1,2,4-triazole sodium potassium, 1-4 carbon atom organic alcohol solvent, add quaternary ammonium salt, reflux for 10 hours, remove insoluble substances by filtration; distill the organic alcohol solvent to obtain transparent colorless 1,2,4-triazole-quaternary ammonium ionic liquid;

[0036] The quaternary ammonium salt includes but is not limited to one of tetrabutylammonium bromide, benzyltriethylammonium chloride, choline chloride, choline bromide;

[0037] 1,2,4-Triazole-quaternary ammonium ionic liquids were prepared by the following five ways, as shown in Table 1 below:

[0038]

[0039] Example 6

[0040] 7.08 kg of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane was mixed with 17.2 kg of 1,2,4-triazole-choline ionic liquid prepared in Example 1, and heated to 150°C for 10 hours, and then cooled to room temperature;

[0041] The oil pump was connected, and vacuum distillation was carried out at -0.095 MPa to -0.1 MPa, and the fraction at 180-190°C was collected, to obtain 6.36 kg of propiconazole with a purity of 98.7%, and a yield of 91.8%. The distillation tailings were a small amount of propiconazole, excess 1,2,4-triazole-choline ionic liquid, and newly formed choline bromide.

[0042] Example 7

[0043] 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 heated to 160°C for 13 hours, and then cooled to room temperature;

[0044] The same vacuum distillation method as in Example 6 was used, to obtain 6.25 kg of propiconazole with a purity of 98.6%, and a yield of 90.1%. The distillation tailings were a small amount of propiconazole, excess 1,2,4-triazole-benzyltriethylammonium ionic liquid, and newly formed benzyltriethylammonium bromide.

[0045] Example 8

[0046] 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 15 kg of DMSO was added, and heated to 160°C for 13 hours, and then cooled to room temperature;

[0047] The same vacuum distillation method as in Example 6 was used, to obtain 5.85 kg of propiconazole with a purity of 98.3%, and a yield of 84.1%. The pre-distillation fraction was a mixture of DMSO and a small amount of propiconazole, and the distillation tailings were a small amount of propiconazole, excess 1,2,4-triazole-benzyltriethylammonium ionic liquid, and newly formed benzyltriethylammonium bromide.

[0048] The present example shows that the addition of organic solvent does not affect the content of propiconazole, but the yield is slightly affected, which is probably due to the lack of reuse of the pre-distillation fraction.

[0049] Example 9

[0050] 7.08 kg of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane was mixed with 3.44 kg of the 1,2,4-triazole-choline ionic liquid prepared in Example 2, and heated to 160°C for 15 hours, and then cooled to room temperature;

[0051] 21.24 kg of dichloromethane was added to the reaction system, and insoluble choline bromide was removed by filtration, and the dichloromethane layer was dechlorinated to obtain 6.55 kg of propiconazole with a content of 97.5%, and a yield of 93.3%.

[0052] Example 10

[0053] 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 heated to 160°C for 13 hours, and then cooled to room temperature;

[0054] 21.24 kg of dichloromethane was added to the reaction system, and insoluble choline bromide was removed by filtration, and the dichloromethane layer was dechlorinated to obtain 6.55 kg of propiconazole with a content of 97.5%, and a yield of 93.3%.

[0055] Example 11

[0056] 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 heated to 160°C for 13 hours, and then cooled to room temperature;

[0057] 21.24 kg of chlorobenzene was added to the reaction system, and insoluble tetrabutylammonium bromide and excess 1,2,4-triazole-tetrabutylammonium ionic liquid were removed by layering, and the chlorobenzene layer was dechlorinated to obtain 6.44 kg of propiconazole with a content of 97.8%, and a yield of 92.1%.

[0058] Example 12

[0059] 7.08 kg of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane was mixed with the distillation tailings during the preparation of Example 2, and heated to 150°C for 10 hours, and then cooled to room temperature;

[0060] The oil pump is connected, and distillation is carried out under reduced pressure at -0.095 MPa to -0.1 MPa, and a fraction of 180-190 DEG C is taken, so that 6.36 kg of propiconazole with a purity of 98.4% is obtained, and the yield is 91.5%. Among them, the distillation tailings are a small amount of propiconazole, excessive 1,2,4-triazole-choline ionic liquid and newly generated choline bromide.

[0061] Example 13

[0062] 7.08 kg of 2-(2,4-dichlorophenyl)-2-chloromethyl-4-propyl-1,3-dioxolane is mixed with 17.2 kg of 1,2,4-triazole-choline ionic liquid prepared in Example 3, and the temperature is raised to 150 DEG C, and the reaction is carried out for 10 hours, and then the temperature is lowered to room temperature;

[0063] The oil pump is connected, and distillation is carried out under reduced pressure at -0.095 MPa to -0.1 MPa, and a fraction of 180-190 DEG C is taken, so that 6.36 kg of propiconazole with a purity of 98.4% is obtained, and the yield is 91.5%. Among them, the distillation tailings are a small amount of propiconazole, excessive 1,2,4-triazole-choline ionic liquid and newly generated choline bromide.

[0064] The present application Figure 7 The present application is a synthesis route map (wherein X is one of chlorine and bromine, M is one of potassium and sodium, R1, R2, R3 and R4 are alkyl groups or aryl groups with 1-7 carbon atoms, and R1, R2, R3 and R4 can be the same or different), and the map is one complete reaction cycle. Specifically, 1,2,4-triazole sodium or 1,2,4-triazole potassium is added to a 1-4 carbon atom organic alcohol solvent, and then a quaternary ammonium salt is added. An ion exchange reaction occurs between the quaternary ammonium salt and the 1,2,4-triazole sodium or 1,2,4-triazole potassium. The halogen in the quaternary ammonium salt combines with the potassium ion or sodium ion in the 1,2,4-triazole sodium or 1,2,4-triazole potassium to form sodium chloride, potassium chloride, sodium bromide or potassium bromide, which precipitates from the entire solution system. The precipitate is removed by filtration, and the 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 1-4 carbon atom organic alcohol solvent. The 1-4 carbon atom organic alcohol solvent is removed by distillation, and 1,2,4-triazole-quaternary ammonium ionic liquid is obtained.

[0065] 1,2,4-triazole-quaternary ammonium ionic liquid and 2-(2,4-dichlorophenyl)-2-halogenomethyl-4-propyl-1,3-dioxolane are subjected to substitution reaction, wherein 1,2,4-triazole in 1,2,4-triazole-quaternary ammonium ionic liquid substitutes halogen in 2-(2,4-dichlorophenyl)-2-halogenomethyl-4-propyl-1,3-dioxolane to form the target product in the present application, i.e. propiconazole, and the remaining quaternary ammonium ion in 1,2,4-triazole-quaternary ammonium ionic liquid combines with the removed halogen to form the initially added quaternary ammonium salt, which can be used in a new cycle reaction, and the target product propiconazole in the reaction system is purified by distillation;

[0066] In addition, the quaternary ammonium salt that can be recycled in the present application may change in the reaction according to the reactants. For details, refer to Example 7. In Example 7, the quaternary ammonium salt participating in the synthesis of 1,2,4-triazole-quaternary ammonium ionic liquid is benzyl triethyl ammonium chloride. In the reaction with sodium 1,2,4-triazole or potassium 1,2,4-triazole, the chlorine element contained in benzyl triethyl ammonium chloride combines with sodium or potassium to precipitate in the solution system and synthesize 1,2,4-triazole-benzyl triethyl ammonium. 1,2,4-triazole-benzyl triethyl ammonium is subjected to substitution reaction with 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane. After benzyl triethyl ammonium combines with bromine in 2-(2,4-dichlorophenyl)-2-halogenomethyl-4-propyl-1,3-dioxolane, it becomes benzyl triethyl bromide, which participates in the subsequent synthesis reaction as a new quaternary ammonium salt.

[0067] If the above reaction uses 2-(2,4-dichlorophenyl)-2-chloromethyl-4-propyl-1,3-dioxolane, the formed substitution product is still benzyl triethyl ammonium chloride.

[0068] From the above description, it can be seen that the halogenated element in the quaternary ammonium salt participating in the new cycle in the present application changes according to the type of halogenomethyl in 2-(2,4-dichlorophenyl)-2-halogenomethyl-4-propyl-1,3-dioxolane.

[0069] Although embodiments of the present application have been shown and described, it is to be understood that various changes, modifications, substitutions and alterations can be made therein without departing from the principles and spirit of the present application, the scope of which is defined by the appended claims and their equivalents.

Claims

1. A method for the solvent-free synthesis of propiconazole via ionic liquid catalysis, characterized in that, Includes the following steps: S1. At room temperature, 1,2,4-triazole sodium or 1,2,4-triazole potassium and a 1-4 carbon atom organic alcohol solvent are mixed, a quaternary ammonium salt is added, the mixture is refluxed for 10 hours, and the insoluble matter is removed by filtration. The 1-4 carbon atom organic alcohol solvent is removed by distillation 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 1,2,4-triazole-quaternary ammonium ionic liquid, heat to 150-160℃, react for 10-15 hours, cool down, and perform post-treatment to obtain propiconazole with a purity of over 98%.

2. The method for solvent-free synthesis of propiconazole via ionic liquid catalysis according to claim 1, characterized in that, 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 1-4 carbon atom organic alcohol solvent to sodium 1,2,4-triazole or potassium 1,2,4-triazole is (5-7):

1.

3. The method for solvent-free synthesis of propiconazole via ionic liquid catalysis according to claim 1, characterized in that, In step S2, the molar ratio of 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 solvent-free synthesis of propiconazole via ionic liquid catalysis according to claim 1, characterized in that, The quaternary ammonium salt in step S1 is one of tetrabutylammonium bromide, benzyltriethylammonium chloride, choline chloride, and choline bromide.

5. The method for solvent-free synthesis of propiconazole via ionic liquid catalysis according to claim 1, characterized in that, The post-processing method in step S2 is one of vacuum distillation or solvent extraction.

6. The method for solvent-free synthesis of propiconazole via ionic liquid catalysis according to claim 5, characterized in that, The pressure conditions for vacuum distillation are -0.095MPa to 0.1MPa, and the temperature conditions are 180-190℃.

7. The method for solvent-free synthesis of propiconazole via ionic liquid catalysis according to claim 5, characterized in that, The organic solvent used for solvent extraction is one of dichloromethane, dichloroethane, or chlorobenzene; the amount of the organic solvent used is three times the mass of 2-(2,4-dichlorophenyl)-2-bromomethyl-4-propyl-1,3-dioxolane.

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