CN107673996A - Method for converting low-activity fenvalerate isomer into high-activity fenvalerate isomer - Google Patents

Abstract

The invention discloses a method for converting a low-activity fenvalerate isomer into a high-activity fenvalerate isomer. The method comprises the following steps: dissolving a low-activity fenvalerate isomer represented by formula I or formula III in an organic solvent, reacting for 12-192 hours to obtain products containing a high-activity fenvalerate isomer represented by formula II or formula IV, respectively, so as to realize the conversion of the low-activity fenvalerate isomer into the high-activity fenvalerate isomer. The organic solvent is a mixed solution of n-hexane and ethanol or a mixed solution of n-hexane and isopropanol. The volume ratio of n-hexane to ethanol is 1.5-9:1. The volume ratio of n-hexane to isopropanol is 1.5-9:1. The method of the present invention is simple to operate, low in cost, can effectively reduce the usage of cypermethrin, and prevent inefficient or ineffective isomers from polluting the environment, can effectively improve the insecticide efficiency, and avoid the occurrence of pesticide damage or drug resistance in crops.

Description

A kind of low activity fenvalerate isomer transforms to high activity fenvalerate isomer method

(1) Technical field

The invention relates to the field of agriculture, in particular to a method for converting a low-activity enantiomer in the pyrethroid insecticide fenvalerate to a high-activity enantiomer.

(2) Background technology

Pesticide refers to a class of drugs used to kill insects, bacteria, and kill harmful animals (or weeds) in order to ensure and promote the growth of plants and crops in agricultural production. Specifically refers to pesticides used in agriculture to control diseases and insect pests, regulate plant growth, and kill weeds. The role of pesticides in promoting modern agriculture is obvious, and pests and diseases have been effectively controlled, making a significant contribution to human survival. However, since pesticides are a class of toxic chemicals, long-term and large-scale use will have certain impacts on environmental ecological security and human health. The air pollution caused by the use of pesticides is becoming more and more serious, and the pollution of pesticides to water bodies cannot be ignored. The long-term intake of low-dose pesticides in people's daily life also causes many chronic adverse effects, such as carcinogenic, teratogenic and mutagenic, nervous system disorders and sexual aberrations, etc. In addition, pesticide soil pollution is one of the most typical examples of pesticide pollution, and the pesticides left in the soil have caused serious phytotoxicity to crops. Pesticides must not only promote the development of agriculture, but must also meet the requirements of environmental protection. Therefore, it is increasingly urgent to develop high-efficiency, low-toxicity, and low-residue pesticide varieties. Due to its high efficacy, less dosage, less waste, safer to crops and environmental ecology, relatively low cost, and strong market competitiveness, monochiral pesticides have attracted the attention of scientists from all over the world and become one of the main directions for the development of pesticides in the 21st century. .

Pesticides with chiral structures (chiral pesticides) account for about 40% of the currently used pesticides. In chiral environments, especially when chiral compounds interact, chiral enantiomers often show different characteristics, sometimes even It shows diametrically opposed properties. From a molecular level point of view, when pesticide compounds interact with organisms, pesticides participate in biochemical reactions. Biological pairs have a chiral structure matching relationship, which makes chiral isomers behave differently. This is the fundamental reason why some chiral bodies show high insecticidal, acaricidal, bactericidal and herbicidal activities, while their enantiomers have low activity or show phytotoxicity. Therefore, the development of a single highly active chiral body or a chiral pesticide without an invalid chiral body is very important, which not only reduces the input of pesticides to nature, but also saves more than half of the raw materials while avoiding drug damage. , the transformation of a single highly active chiral pesticide in the environment is also a major issue worthy of our further in-depth study, in order to minimize the problem of pesticide residue pollution.

Fenvalerate, commonly known as fenvalerate, is a synthetic pyrethroid insecticide with high biological activity and non-three-membered ring structure developed by Sumitomo Chemical Industry Co., Ltd., Japan. The chemical name is (RS)- α-cyano-3-phenoxybenzyl (RS)-2-(4-chlorophenyl)-3-methylbutyrate. The original drug is a yellow to brown viscous liquid, part of which crystallizes out at room temperature and decomposes during distillation. Stable to heat and humidity, relatively stable in acidic medium, rapidly hydrolyzed in alkaline medium. This product is a broad-spectrum high-efficiency insecticide with rapid action and strong knockdown power. It is mainly used to kill a variety of cotton pests, such as cotton bollworm and cotton aphid. It is widely used in the control of tobacco, soybeans, corn, and fruit trees. , vegetable pests, and can also be used to control pests in livestock and storage. Fenvalerate is a moderately toxic insecticide, the acute oral LD50 of rats is 451mg/kg, the acute percutaneous LD50 of rats is >5000mg/kg, and the acute inhalation LC50 of rats is >101mg/m ³ , on rabbit skin Slightly irritating, moderately irritating to eyes. No mutagenic, teratogenic and carcinogenic effects. Highly toxic to bees, fish, poultry, etc.

The structure of pyrethroid pesticides is relatively complex, and the daily use is generally racemic, of which only a few isomers have good biological activity, while other isomers are either low or ineffective, such as fenpropathrin There are two isomers, the insecticidal activity of the S body is 50 times that of the R body. From the chemical structure of fenvalerate, it can be seen that fenvalerate has 2 chiral carbon atoms, so there are 4 optical isomers, the ester with S acid structure has strong insecticidal activity, and the ester of R acid has almost no insecticidal activity. activity, and the insecticidal activity of the ester with S alcohol structure is stronger than that of R alcohol, wherein the insecticidal activity is S acid-S alcohol>S acid-R alcohol>R acid-S alcohol>R acid-R alcohol, wherein The biological activity of SS isomers is 2-4 times higher than other isomers. Low or ineffective isomers will not only reduce the efficacy of medicines, but also pollute the environment, and even cause phytotoxicity or resistance to crops.

The methods for obtaining chiral compounds of a single enantiomer include chiral source synthesis and asymmetric synthesis. The chiral source synthesis uses the chiral compound of a single enantiomer as a raw material to synthesize a single enantio However, due to the limited types of natural chiral substances, the synthesis of various target products is greatly restricted. The asymmetric synthesis method is under the action of a catalyst or an enzyme, which can obtain an excess of a single enantiomer chiral compound. This method has been greatly developed in the past 20 years, and some reactions have begun to be used in industrial production, but to achieve There are still many difficulties in the reaction with high optical rotation yield. Biological asymmetric synthesis has high enantioselectivity, but it has high requirements for substrates, slow reaction and difficult product separation.

The common dosage form of fenvalerate in the market is 20% fenvalerate emulsifiable concentrate, which is a dosage form with the largest output in pesticide products, and is produced by oil-soluble pesticide raw materials and emulsifiers and other additives in organic solvents It is a transparent true solution, which can form an emulsifiable emulsion after being added to water. The active ingredients of pesticides are dissolved in the solvent and dispersed in water as very fine oil droplets. However, most of the existing emulsifiable concentrate products are processed with aromatic hydrocarbon organic solvents, and mixed xylenes are the most selected, because they have good solubility to most of the original pesticides and can enhance the resistance of the medicament to the epidermis of organisms. Penetration ability, which can improve drug efficacy. Since aromatic hydrocarbon solvents have been listed as environmental monitoring substances, emulsifiable concentrate formulations are facing a situation of being phased out and replaced by other formulations.

(3) Contents of the invention

In order to reduce the use amount of fenvalerate, and prevent low-efficiency or ineffective isomers from polluting the environment, and even cause phytotoxicity or resistance to crops, the purpose of the present invention is to provide a low-activity fenvalerate isomer Method for conversion to highly active esfenvalerate isomers.

The technical scheme adopted in the present invention is:

A method for converting low-activity esvalerate isomers to high-activity isomers, characterized in that: the method is specifically carried out according to the following steps:

Dissolving the low-activity fenvalerate isomer shown in formula I or formula III in an organic solvent, and reacting for 12 to 192 hours to obtain the high-activity fenvalerate isomer shown in formula II or formula IV respectively The product realizes the conversion of low-activity fenvalerate isomers to high-activity fenvalerate isomers; the organic solvent is a mixed solution of n-hexane and ethanol or a mixed solution of n-hexane and isopropanol; The volume ratio of n-hexane to ethanol is 1.5-9:1; the volume ratio of described n-hexane to isopropanol is 1.5-9:1;

Further, the concentration of the single low-activity esvalerate isomer represented by formula I or formula III is 10 mg/L-1000 mg/L.

Further, the volume ratio of the n-hexane to ethanol is 6:4.

Further, the volume ratio of the n-hexane to Virahol is 6:4.

Further, the reaction product obtained in the present invention is detected by high-performance liquid chromatography, and the high-performance liquid chromatography adopts a normal-phase chromatographic column CHIRALCEL OJ-H column, and the mobile phase is n-hexane: ethanol=90:10, and the flow rate of the mobile phase is The injection volume is 0.6ml/min, the injection volume is 20ul, and the detection wavelength is 230nm. According to the chromatographic peak, the content of formula I and formula II or the content of formula III and IV in the same solution can be obtained.

Compared with prior art, the beneficial effect of the present invention is:

The method of the present invention is easy to operate and low in cost, and can effectively reduce the usage amount of the racemic compound fenvalerate, and the chiral pesticide can achieve higher efficacy with a lower dose, reducing the need for pesticides to The input in the field and the prevention of low-efficiency or ineffective isomers from polluting the environment can effectively improve the insecticidal efficiency, avoid phytotoxicity or resistance of crops, save a lot of raw materials, and improve economic and social benefits.

(4) Description of drawings

Fig. 1 is the conversion diagram of 100% low activity αR-2R-fenvalerate to high activity αS-2R-fenvalerate in different ratios of n-hexane: ethanol.

Fig. 2 is the conversion diagram of 100% low-activity αR-2R-fenvalerate to high-activity αS-2R-fenvalerate in different ratios of n-hexane:isopropanol.

Fig. 3 is the conversion diagram of 100% low-activity αS-2R-fenvalerate to high-activity αS-2S-fenvalerate in different ratios of n-hexane:ethanol.

Fig. 4 is the conversion diagram of 100% low-activity αS-2R-fenvalerate to high-activity αS-2S-fenvalerate in different ratios of n-hexane:isopropanol.

Figure 5-Figure 8 CD spectra of four isomers of fenvalerate, αR-2R, αR-2S, αS-2R, αS-2S.

(5) Specific implementation methods

Below in conjunction with specific example, further set forth the present invention. It should be understood that these embodiments are only used to illustrate the present invention, and are not intended to limit the scope of the claims, and other alternatives conceivable by those skilled in the art are within the scope of the claims of the present invention.

Embodiment 1: take 5mg of αR-2R-fenvalerate, dissolve in 500ml n-hexane: ethanol is 9:1 in the solvent, obtain the αR-2R-fenvalerate solution of 10mg/L, put into 4 Store in the refrigerator at ℃, use high performance liquid chromatography to detect the solution at 12, 24, 48, 96, and 192 hours, and judge the isomer corresponding to the chromatographic peak and its content according to the peak time of the chromatographic peak and compare with the CD spectrum. The results are shown in Figure 2. The results show that in a solvent of n-hexane:ethanol at a ratio of 9:1, 100% of αR-2R-fenvalerate will be partially converted into highly active αS-2R-fenvalerate over time For pyrethrin, the longer the time, the more the conversion becomes more stable. At 192h, the content of αR-2R-fenvalerate was 57%, and that of αS-2R-fenvalerate was 43%. Fenvalerate contains four isomers, and the activity size is SS>SR>RS>RR. The insecticidal activity of RR type is extremely low, or even has no activity. It can be transformed into SR type with high activity to reduce the use of pesticides.

Embodiment 2: Weigh 5mg of αR-2R-fenvalerate, dissolve in 500ml n-hexane: ethanol is 8:2 in the solvent, obtain the αR-2R-fenvalerate solution of 10mg/L, put into 4 Store in the refrigerator at ℃, use high performance liquid chromatography to detect the solution at 12, 24, 48, 96, and 192 hours, and judge the isomer corresponding to the chromatographic peak and its content according to the peak time of the chromatographic peak and compare with the CD spectrum. The results are shown in Figure 2. The results show that in a solvent of n-hexane:ethanol at 8:2, 100% of αR-2R-fenvalerate will be partially converted into highly active αS-2R-fenvalerate over time For pyrethrin, the longer the time, the more the transformation becomes more stable. At 192h, the content of αR-2R-fenvalerate was 52%, and that of αS-2R-fenvalerate was 48%.

Embodiment 3: Weigh 5mg of αR-2R-fenvalerate, dissolve in 500ml n-hexane: ethanol is a solvent of 6:4, obtain 10mg/L αR-2R-fenvalerate solution, put into 4 Store in the refrigerator at ℃, use high performance liquid chromatography to detect the solution at 12, 24, 48, 96, and 192 hours, and judge the isomer corresponding to the chromatographic peak and its content according to the peak time of the chromatographic peak and compare with the CD spectrum. The results are shown in Figure 2. The results show that in the solvent of n-hexane:ethanol 6:4, 100% of αR-2R-fenvalerate will be partially converted into highly active αS-2R-fenvalerate over time For pyrethrin, the longer the time, the more stable it becomes. At 192 hours, the content of αR-2R-fenvalerate was 50%, and that of αS-2R-fenvalerate was 50%. Figure 2 shows that the higher the ethanol content in the solvent, the higher the conversion rate of αR-2R-esfenvalerate and the faster the conversion rate.

Example 4: Weigh 5 mg of αR-2R-fenvalerate, dissolve it in 500ml of n-hexane:isopropanol as a solvent of 9:1, obtain 10mg/L of αR-2R-fenvalerate solution, put Store in a refrigerator at 4°C, and detect the solution by high performance liquid chromatography at 12, 24, 48, 96, and 192 hours. According to the time when the chromatographic peak emerges, compare the CD spectrum to determine the isomer corresponding to the chromatographic peak and its content. The results are shown in Figure 3. The results show that in the solvent of n-hexane: isopropanol with a ratio of 9:1, 100% of αR-2R-fenvalerate will be partially converted into highly active αS-2R- For fenvalerate, at 192h, the content of αR-2R-fenvalerate was 58%, and that of αS-2R-fenvalerate was 42%.

Example 5: Weigh 5 mg of αR-2R-fenvalerate, dissolve it in 500ml of n-hexane: isopropanol in a solvent of 6:4, obtain 10 mg/L of αR-2R-fenvalerate solution, put Store in a refrigerator at 4°C, and detect the solution by high performance liquid chromatography at 12, 24, 48, 96, and 192 hours. According to the time when the chromatographic peak emerges, compare the CD spectrum to determine the isomer corresponding to the chromatographic peak and its content. The results are shown in Figure 3. The results show that in the solvent of n-hexane:isopropanol 6:4, 100% of αR-2R-fenvalerate will be partially converted into highly active αS-2R- For fenvalerate, at 192h, the content of αR-2R-fenvalerate was 58%, and that of αS-2R-fenvalerate was 42%. Figure 3 shows that the change of isopropanol content has no significant impact on the conversion of αR-2R-fenvalerate, and the final conversion rate and conversion rate are similar.

Embodiment 6: Weigh 5mg of αR-2R-fenvalerate, dissolve in 500ml n-hexane: ethanol is 9:1 solvent, obtain 10mg/L αR-2R-fenvalerate solution, put into 4 Store in the refrigerator at ℃, use high performance liquid chromatography to detect the solution at 12, 24, 48, 96, and 192 hours, and judge the isomer corresponding to the chromatographic peak and its content according to the peak time of the chromatographic peak and compare with the CD spectrum. The results are shown in Figure 4. The results show that in a solvent of n-hexane:ethanol at a ratio of 9:1, 100% of αS-2R-fenvalerate will be partially converted into highly active αS-2S-fenvalerate over time For pyrethrin, the longer the time, the more stable it becomes. At 192 hours, the content of αR-2R-fenvalerate was 53%, and that of αS-2R-fenvalerate was 47%. The highest activity of the four isomers of fenvalerate is SS, that is, cis-fenvalerate, and the toxicity of cis-fenvalerate to esters and Fen-S sensitive strains is 8.7 times higher than that of fenvalerate. The toxicity of cis-fenvalerate was 113.1 and 28.5 times higher than that of fenvalerate in the two resistant lines Fen-R and Shandong Yanggu S6 bred indoors with fenvalerate. In terms of resistance multiples, the resistance to fenvalerate is 81.8 to 2142.8 times for the resistant strains bred indoors and the resistant populations collected from cotton fields, and 22.1 to 164.6 times for esfenvalerate. times, the greater the resistance, the greater the difference in toxicity between esfenvalerate and esfenvalerate, and the insecticidal activity of esfenvalerate is much higher than that of esfenvalerate.

Example 7: Weigh 5mg of αR-2R-fenvalerate, dissolve it in 500ml of n-hexane: ethanol as a solvent of 8:2, obtain 10mg/L of αR-2R-fenvalerate solution, put it into 4 Store in the refrigerator at ℃, use high performance liquid chromatography to detect the solution at 12, 24, 48, 96, and 192 hours, and judge the isomer corresponding to the chromatographic peak and its content according to the peak time of the chromatographic peak and compare with the CD spectrum. The results are shown in Figure 4. The results show that in a solvent of n-hexane:ethanol at 8:2, 100% of αS-2R-fenvalerate will be partially converted into highly active αS-2S-fenvalerate over time For pyrethrin, the longer the time, the more stable it becomes. At 192 hours, the content of αR-2R-fenvalerate was 53%, and that of αS-2R-fenvalerate was 47%.

Example 8: Weigh 5mg of αR-2R-fenvalerate, dissolve it in 500ml of n-hexane: ethanol as a solvent of 6:4, obtain 10mg/L of αR-2R-fenvalerate solution, put it into 4 Store in the refrigerator at ℃, use high performance liquid chromatography to detect the solution at 12, 24, 48, 96, and 192 hours, and judge the isomer corresponding to the chromatographic peak and its content according to the peak time of the chromatographic peak and compare with the CD spectrum. The results are shown in Figure 4. The results show that in the solvent of n-hexane:ethanol at 6:4, 100% of αS-2R-fenvalerate will be partially converted into highly active αS-2S-fenvalerate over time For pyrethrin, the longer the time, the more stable it becomes. At 192 hours, the content of αR-2R-fenvalerate was 50%, and that of αS-2R-fenvalerate was 50%.

Example 9: Weigh 5 mg of αR-2R-fenvalerate, dissolve it in 500ml of n-hexane: isopropanol in a solvent of 6:4, obtain 10 mg/L of αR-2R-fenvalerate solution, put Store in a refrigerator at 4°C, and detect the solution by high performance liquid chromatography at 12, 24, 48, 96, and 192 hours. According to the time when the chromatographic peak emerges, compare the CD spectrum to determine the isomer corresponding to the chromatographic peak and its content. The results are shown in Figure 5. The results show that in the solvent of n-hexane: isopropanol with a ratio of 9:1, 100% of αS-2R-fenvalerate will be partially converted into highly active αS-2S- Fenvalerate, the longer the time, the more stable it becomes. At 192 hours, the content of αS-2R-fenvalerate was 68%, and that of αS-2S-fenvalerate was 32%.

Example 10: Weigh 5 mg of αR-2R-fenvalerate, dissolve it in 500ml of n-hexane: isopropanol in a solvent of 6:4, obtain 10 mg/L of αR-2R-fenvalerate solution, put Store in a refrigerator at 4°C, and detect the solution by high performance liquid chromatography at 12, 24, 48, 96, and 192 hours. According to the time when the chromatographic peak emerges, compare the CD spectrum to determine the isomer corresponding to the chromatographic peak and its content. The results are shown in Figure 5. The results show that in the solvent of n-hexane:isopropanol 6:4, 100% of αS-2R-fenvalerate will be partially converted into highly active αS-2S- Fenvalerate tends to be more stable as time goes by. At 192 hours, the content of αS-2R-fenvalerate is 58%, and that of αS-2S-fenvalerate is 42%.

Claims (4)

1. a method for converting low-activity esvalerate isomers to high-activity esvalerate isomers, characterized in that: the method is specifically carried out according to the following steps: Dissolving the low-activity fenvalerate isomer shown in formula I or formula III in an organic solvent, and reacting for 12-192 hours to obtain the high-activity fenvalerate isomer shown in formula II or formula IV respectively The product realizes the conversion of low-activity fenvalerate isomers to high-activity fenvalerate isomers; the organic solvent is a mixed solution of n-hexane and ethanol or a mixed solution of n-hexane and isopropanol; The volume ratio of n-hexane to ethanol is 1.5-9:1; the volume ratio of n-hexane to isopropanol is 1.5-9:1. 2. The method according to claim 1, characterized in that: the concentrations of the low-activity esvalerate isomers represented by the formula I or formula III are respectively 10-1000 mg/L organic solvent. 3. the method for claim 1 is characterized in that: the volume ratio of described n-hexane and ethanol is 6:4. 4. the method for claim 1 is characterized in that: the volume ratio of described n-hexane and Virahol is 6:4.