阅读说明：本技术 一种低含量杂质的乙蒜素原药、制备方法及其用途 (Ethylicin original medicine with low impurity content, preparation method and application thereof ) 是由 薛照先 何昆明 林光东 于 2019-10-25 设计创作，主要内容包括：本发明涉及一种低含量杂质的乙蒜素原药、制备方法及其用途,所述乙蒜素原药中有效成分乙蒜素的重量含量≥95％,所述乙蒜素原药中杂质二乙基二硫醚的重量含量小于等于1％。所述乙蒜素原药可以通过将二乙基二硫醚溶液、冰醋酸和氧化性原料输入到微反应器制备得到。本发明的乙蒜素原药中有效成分乙蒜素的含量提高,其中的杂质二乙基二硫醚降低,杂质二乙基二硫醚是对植物有药害或者是增加药剂毒性的物质,该杂质的降低提高了乙蒜素原药对作物的安全性。本发明的乙蒜素原药由于纯度高和杂质含量低,所以使得其能够有效提高其防治效果和显著降低其对敏感作物或作物的敏感生长期的药害。(The invention relates to a raw ethylicin with low impurity content, a preparation method and application thereof, wherein the weight content of an effective component ethylicin in the raw ethylicin is more than or equal to 95%, and the weight content of impurity diethyl disulfide in the raw ethylicin is less than or equal to 1%. The ethylicin technical can be prepared by inputting diethyl disulfide solution, glacial acetic acid and oxidizing raw materials into a microreactor. The content of the active ingredient ethylicin in the ethylicin raw pesticide is improved, the impurity diethyl disulfide is reduced, the impurity diethyl disulfide is a substance which has phytotoxicity to plants or increases the toxicity of the pesticide, and the reduction of the impurity improves the safety of the ethylicin raw pesticide to the crops. The ethylicin technical of the invention has high purity and low impurity content, so that the control effect of the ethylicin technical can be effectively improved and the phytotoxicity of the ethylicin technical to sensitive crops or sensitive growth periods of the crops can be obviously reduced.)

1. The ethylicin crude drug comprises the effective component of more than or equal to 95% by weight of ethylicin and less than or equal to 1% by weight of impurity diethyl disulfide.

2. The raw ethylicin compound according to claim 1, wherein the weight content of the effective component ethylicin in the raw ethylicin compound is not less than 98%, and the weight content of the impurity diethyl disulfide in the raw ethylicin compound is not more than 0.5%.

3. Ethylicin bulk drug according to claim 1 or 2, characterized in that it is prepared by the following method:

inputting a diethyl disulfide solution, glacial acetic acid and an oxidizing raw material into a microreactor, inputting a gas-liquid mixture generated after reaction of the microreactor into a gas-liquid separator, performing gas-liquid separation on the gas-liquid mixture in the gas-liquid separator, inputting liquid into a liquid separation tank, and separating a water phase to obtain an oil phase, namely the ethylicin original drug; or the reaction is continued while the gas is separated in the gas-liquid separator, the liquid is input into a liquid separating tank after the reaction is continued, the oil phase obtained after the water phase is separated is the ethylicin technical product, or the liquid is input into a coil reactor or a microreactor for the reaction is continued after the gas is separated in the gas-liquid separator, the gas-liquid mixture is input into the gas-liquid separator after the reaction, the liquid with the gas separated is input into the liquid separating tank, and the oil phase obtained after the water phase is separated is the ethylicin technical product.

4. The raw ethylicin drug according to claim 3, wherein the oxidative raw material is a nitric acid solution or a hydrogen peroxide solution, or a mixed solution of the nitric acid solution and the hydrogen peroxide solution.

5. The raw ethylicin hydrochloride according to claim 4, wherein the diethyl disulfide solution, the glacial acetic acid and the oxidizing raw materials are input into the microreactor in a way that:

(1) respectively inputting a diethyl disulfide solution, glacial acetic acid and an oxidizing raw material into a microreactor;

(2) mixing glacial acetic acid and diethyl disulfide to form a mixture, inputting the mixture into a microreactor, and independently inputting oxidizing raw materials into the microreactor; or the like, or, alternatively,

(3) when the oxidizing raw material is a liquid oxidizing raw material, glacial acetic acid and the oxidizing raw material are mixed to form a mixture, the mixture is input into the microreactor, and the diethyl disulfide is independently input into the microreactor.

6. The raw ethylicin hydrochloride according to claim 3, wherein the diethyl disulfide solution, the glacial acetic acid and the oxidizing raw material are pressurized before being fed into the microreactor, so as to increase the pressure of the raw material fed into the microreactor.

7. An allicin prodrug according to claim 3, wherein the diethyldisulfide solution, glacial acetic acid and the oxidizing raw material are passed through a check valve before being fed into the microreactor, and are fed into the microreactor again after being passed through the check valve.

8. A raw ethirimol according to claim 3, wherein the molar ratio of the diethyl disulfide as the active ingredient in the diethyl disulfide solution to glacial acetic acid is (7-9):1, and when the oxidizing material is a nitric acid solution, the molar ratio of the diethyl disulfide as the active ingredient in the diethyl disulfide solution to the nitric acid as the active ingredient in the nitric acid solution is 1: (1.4-2.1); when the oxidizing material is hydrogen peroxide, the molar ratio of the active ingredient diethyl disulfide in the diethyl disulfide solution to the active ingredient hydrogen peroxide in the nitric acid solution is 1: (2.3-3.4).

9. An ethylicin prodrug according to claim 8, wherein the concentration by mass of the diethyldisulfide solution is 75 to 99 wt%, the concentration by mass of the nitric acid solution is 35 to 65 wt%, and the concentration by mass of the hydrogen peroxide is 20 to 50 wt%.

10. The ethylicin bulk drug according to claim 3, wherein the microreactor is a microchannel reactor, the cross-sectional area of a fluid channel in the microchannel reactor is 100 to 1000000 square micrometers, preferably, the cross-sectional area of the fluid channel is 100 to 100000 square micrometers, particularly preferably, the cross-sectional area of the fluid channel is 100 to 20000 square micrometers, and the total volume of the fluid channel is 50 to 500 ml.

11. Use of a technical body of ethylicin according to any one of claims 1 to 10, characterized in that the use is: the ethylicin technical improves the control effect on crop diseases and reduces the phytotoxicity on crops.

Technical Field

The invention belongs to the field of pesticide preparation, and particularly relates to a ethylicin original drug with low impurity content, a preparation method and application thereof.

Background

The chemical name of ethylicin is ethyl thiosulfonate, which belongs to low-grade toxic bactericide. Has the function of regulating the growth of plants, can stimulate the growth of crops, strengthen roots and seedlings, promote germination, improve the germination rate, increase the yield and improve the quality, and is a preferred raw material of the compound bactericide pesticide. The ethylicin is mainly used for crops such as wheat, rice, cotton, fruit trees, vegetables, melons, flowers, medicinal materials, tea leaves and the like, and is used for preventing and treating rice seedling rot, bakanae disease, rice blast, bacterial leaf blight, wheat smut, stripe disease, cotton wilt, verticillium wilt, fruit tree ring spot, anthracnose, leaf spot, epidemic diseases, bacterial wilt, gummy stem blight, anthracnose crop seedling stage damping off, damping-off, root rot and the like of fruits and vegetables.

The concentration of the ethylicin raw pesticide is generally 80 wt% and 90 wt%, impurities in the ethylicin have important influence on the application of the ethylicin raw pesticide, on one hand, the pesticide effect of the ethylicin can be influenced, and on the other hand, phytotoxicity can be caused on sensitive crops or sensitive stages of the crops, such as seedling stage, flowering stage and the like, so that adverse effect on the growth of the crops is generated.

Therefore, the improvement of the purity of the ethylicin technical material and the reduction of the impurity of the ethylicin technical material are urgently needed, and the invention provides the ethylicin technical material with high concentration and low impurity and a preparation method thereof.

Disclosure of Invention

In order to solve the technology, the invention provides a raw ethylicin, wherein the weight content of an effective component, namely the ethylicin, in the raw ethylicin is more than or equal to 95%, and the weight content of impurity, namely diethyl disulfide, in the raw ethylicin is less than or equal to 1%. Preferably, the weight content of the active ingredient ethylicin in the ethylicin raw drug is more than or equal to 98 percent, and the weight content of the impurity diethyl disulfide in the ethylicin raw drug is less than or equal to 0.5 percent.

Preferably, the ethylicin technical is prepared by the following method:

inputting a diethyl disulfide solution, glacial acetic acid and an oxidizing raw material into a microreactor, inputting a gas-liquid mixture generated after reaction of the microreactor into a gas-liquid separator, performing gas-liquid separation on the gas-liquid mixture in the gas-liquid separator, inputting liquid into a liquid separation tank, and separating a water phase to obtain an oil phase, namely the ethylicin original drug; or the reaction is continued while the gas is separated in the gas-liquid separator, the liquid is input into a liquid separating tank after the reaction is continued, the oil phase obtained after the water phase is separated is the ethylicin technical product, or the liquid is input into a coil reactor or a microreactor for the reaction is continued after the gas is separated in the gas-liquid separator, the gas-liquid mixture is input into the gas-liquid separator after the reaction, the liquid with the gas separated is input into the liquid separating tank, and the oil phase obtained after the water phase is separated is the ethylicin technical product.

Preferably, in the above scheme of the raw ethylicin, the oxidizing raw material is a nitric acid solution or a hydrogen peroxide solution, or a mixed solution of the nitric acid solution and the hydrogen peroxide solution.

Preferably, in the above scheme of the raw allicin, the input of the diethyl disulfide solution, the glacial acetic acid and the oxidizing raw material into the microreactor is as follows:

(1) respectively inputting a diethyl disulfide solution, glacial acetic acid and an oxidizing raw material into a microreactor;

(2) mixing glacial acetic acid and diethyl disulfide to form a mixture, inputting the mixture into a microreactor, and independently inputting oxidizing raw materials into the microreactor; or the like, or, alternatively,

(3) when the oxidizing raw material is a liquid oxidizing raw material, glacial acetic acid and the oxidizing raw material are mixed to form a mixture, the mixture is input into the microreactor, and the diethyl disulfide is independently input into the microreactor.

Preferably, in the above embodiment of the raw allicin, the diethyl disulfide solution, glacial acetic acid and the oxidizing raw material are pressurized before being input into the microreactor, so as to increase the pressure of the raw material input into the microreactor.

Preferably, in the above scheme of the raw allicin, the diethyl disulfide solution, the glacial acetic acid and the oxidizing raw material are input into the microreactor, pass through the check valve before being input into the microreactor, and then are input into the microreactor again after passing through the check valve.

A check valve is also known as a check valve, or a return valve, the main purpose of which is that after a liquid or gas has passed through the valve, the liquid or gas does not flow back if the pressure behind the valve is greater than the pressure in front of the valve.

Preferably, in the above embodiment of the raw allicin drug, the molar ratio of the active ingredient diethyl disulfide to glacial acetic acid in the diethyl disulfide solution is (7-9):1, and when the oxidizing raw material is a nitric acid solution, the molar ratio of the active ingredient diethyl disulfide in the diethyl disulfide solution to the active ingredient nitric acid in the nitric acid solution is 1: (1.4-2.1); when the oxidizing material is hydrogen peroxide, the molar ratio of the active ingredient diethyl disulfide in the diethyl disulfide solution to the active ingredient hydrogen peroxide in the nitric acid solution is 1: (2.3-3.4).

Preferably, in the above scheme of the raw allicin, the mass concentration of the diethyl disulfide solution is 75-99 wt%, the mass concentration of the nitric acid solution is 35-65 wt%, and the mass concentration of the hydrogen peroxide is 20-50 wt%.

Preferably, in the above scheme of the raw ethylicin, the microreactor is a microchannel reactor, and a cross-sectional area of a fluid channel in the microchannel reactor is 100 to 1000000 square micrometers, preferably, the cross-sectional area of the fluid channel is 100 to 100000 square micrometers, particularly preferably, the cross-sectional area of the fluid channel is 100 to 20000 square micrometers, and the total volume of the fluid channel is 50 to 500 ml.

The invention also provides the application of the ethylicin technical, which is characterized in that the ethylicin technical improves the control effect on crop diseases and reduces the phytotoxicity on crops.

Preferably, in the above use, the crop diseases are crop bacterial diseases or crop fungal diseases;

preferably, in the above application, the phytotoxicity of the crops is one or more of phytotoxicity of roots of the crops, phytotoxicity of stems and leaves of the crops or phytotoxicity of fruits of the crops.

Preferably, in the above usage, the crop is one or more of grain crops, coarse cereal crops, medicinal materials, fruit trees or vegetables.

The invention has the advantages of

1. The content of the active ingredient ethylicin in the ethylicin raw pesticide is improved, the impurity diethyl disulfide is reduced, the impurity diethyl disulfide is a substance which has phytotoxicity to plants or increases the toxicity of the pesticide, and the reduction of the impurity improves the safety of the ethylicin raw pesticide to the crops.

2. The ethylicin technical is prepared by setting a micro-reactor process method and system, the purity of the ethylicin technical prepared by the method or the system is high, and the content of impurity diethyl disulfide is very low, so that the quality of the ethylicin technical is improved.

3. The ethylicin technical of the invention has high purity and low impurity content, so that the control effect of the ethylicin technical can be effectively improved and the phytotoxicity of the ethylicin technical to sensitive crops or sensitive growth periods of the crops can be obviously reduced.

Detailed Description

The content detection of the ethylicin adopts a ethylicin standard sample to carry out the detection by an internal standard method, and the content detection of the diethyl disulfide adopts a diethyl disulfide standard sample to carry out the detection by the internal standard method. The microreactors used in the examples described below were microchannel reactors with a microchannel cross-sectional area of 600 square microns and a total microchannel volume of 210 ml.

First, preparation example

Preparation example 1 conventional method for preparing ethylicin

Putting 450L diethyl disulfide solution with concentration of 85% and 50L glacial acetic acid into a gas-liquid separator with a coil pipe and a stirrer to form a base solution, continuously stirring the base solution, heating the base solution to 80 ℃ and maintaining the temperature, then dripping 45% nitric acid solution into the base solution, dripping 710L nitric acid solution at an average speed, keeping stirring and constant temperature of 80 ℃ in the dripping process, continuously stirring at constant temperature for 5 hours after finishing dripping, continuously recovering nitric oxide gas in the reaction process, keeping the gas-liquid separator in a micro-negative pressure state, cooling after the reaction is finished, cooling to 40 ℃, inputting a reaction product into a liquid separation tank, separating out a water phase to obtain an oil phase, namely ethylicin crude drug (ethylicin crude drug A), detecting that the concentration of the ethylicin crude drug is 91.8%, calculating the yield based on diethyl disulfide, and the yield of the ethylicin is 89.5%, the weight content of diethyldisulfide was found to be 2.75%.

Preparation example 2 preparation of ethylicin Using nitric acid solution and microreactor

Preparing 85% diethyl disulfide solution, glacial acetic acid and 45% nitric acid solution, mixing glacial acetic acid and diethyl disulfide solution in a weight ratio of 5:95 to obtain a mixed solution, pressurizing the mixed solution and the nitric acid solution by a pressure pump respectively at a pressure of 0.15Mpa, introducing the mixed solution and the nitric acid solution into a microreactor respectively after passing through a check valve, introducing the mixed solution into the microreactor at a speed of 500L/h, introducing the nitric acid solution into the microreactor at a speed of 710L/h, maintaining the temperature of the microreactor at 80-100 ℃, introducing a gas-liquid mixture passing through the microreactor into a gas-liquid separator, stirring at a constant temperature of 80 ℃ in gas-liquid separation to continue reacting for 1.5 h, cooling to 40 ℃ after the reaction is finished, introducing the liquid into a liquid separation tank, and separating out a water phase and an oil phase after layering, the oil phase is ethylicin raw drug (ethylicin raw drug B), the concentration of the ethylicin raw drug is 98.4 percent, the yield of the ethylicin is 98.9 percent, and the content of diethyl disulfide in the ethylicin raw drug is 0.38 percent.

Preparation example 3 preparation of ethylicin Using Hydrogen peroxide solution and microreactor

Preparing 85% diethyl disulfide solution, glacial acetic acid and 45% hydrogen peroxide solution, mixing glacial acetic acid and diethyl disulfide solution at a weight ratio of 5:95 to obtain a mixed solution, pressurizing the mixed solution and the hydrogen peroxide solution by a pressure pump respectively at a pressure of 0.15Mpa, introducing the mixed solution and the hydrogen peroxide solution into a microreactor respectively after passing through a check valve, introducing the mixed solution into the microreactor at a speed of 500L/h, introducing the hydrogen peroxide solution into the microreactor at a speed of 870L/h, maintaining the temperature of the microreactor in a cooling system at 80-100 ℃, introducing the gas-liquid mixture passing through the microreactor into a gas-liquid separator, stirring at a constant temperature of 80 ℃ during separation, continuing to react for 2.5 h, cooling to 40 ℃ after the reaction is finished, then introducing into a liquid separation tank, separating out a water phase and an oil phase after layering, the oil phase is ethylicin original drug (ethylicin original drug C), the concentration of the ethylicin original drug is detected to be 98.2%, the yield of the ethylicin is detected to be 98.8%, and the content of diethyl disulfide in the ethylicin original drug is detected to be 0.46%.

Second, technical application example

The ethylicin technical A, the ethylicin technical B and the ethylicin technical C prepared in preparation examples 1-3 are applied to prepare 30% ethylicin emulsifiable solution A, 30% ethylicin emulsifiable solution B and 30% ethylicin emulsifiable solution C, the prepared emulsifiable solutions A, B are the same as the C auxiliary agents, and the difference of the control effects of the three technical on crop diseases and the phytotoxicity condition after being applied to crops are tested.

Application example 1 control of watermelon wilt

The method comprises the steps of applying 30% ethylicin missible oil A, 30% ethylicin missible oil B and 30% ethylicin missible oil C to control watermelon fusarium wilt, irrigating roots and applying pesticides in a watermelon seedling stage, wherein test treatment is 4, three pesticide treatment and clear water contrast treatment are carried out, each treatment is 3 times, each repetition is 1 square meter, the pesticide application frequency is 2 times, the first pesticide application is carried out 10 days after watermelon is planted in a seedbed and applied to a soil position where seeds are planted, and the second pesticide application is carried out in a watermelon 4-leaf stage (5 days before transplantation). The concentration of the pesticide for each time of pesticide application is 2000 times of that of the ethylicin emulsifiable solution. The control is clear water, and the clear water dosage and the medicament dosage are the same. The control effect of watermelon fusarium wilt was investigated 10 days after transplantation and 40 days after transplantation. The investigation adopts a whole-plant investigation, and the number of plants with blight diseases is investigated to calculate the control effect of watermelon blight. The specific results are shown in table 1 below.

TABLE 1 Effect of ethylicin agents on the prevention and treatment of watermelon fusarium wilt

Medicament	10 days of transplantation control (%)	40 days of transplantation control (%)
			30% ethylicin emulsifiable concentrate A	85.4	82.3
30% ethylicin emulsifiable concentrate B	94.2	94.1
			30% ethylicin emulsifiable concentrate C	94.8	93.2
Clear water (control)	---	---

As can be seen from the above Table 1, the effect of the prepared preparation is also enhanced due to the increase of the purity of the raw ethylicin, and especially the effect of preventing and treating the watermelon fusarium wilt is improved.

Application example 2 phytotoxicity of ethylicin Agents to crops

The method comprises the following steps of applying 30% ethylicin missible oil A, 30% ethylicin missible oil B and 30% ethylicin missible oil C to 3-leaf stage of cucumber, wherein the application multiple is 800 times of liquid, the application mode is spraying, three treatments are carried out, each treatment is carried out three times, each treatment is carried out 0.5 square meter seedbed, the phytotoxicity condition of cucumber seedlings is investigated 4 days after application, the total number of the cucumber seedlings which are carried out each time is counted before application, and the investigation indexes after application determine whether phytotoxicity occurs according to the following cucumber seedling conditions:

and (4) speckle: brown spots, yellow spots, scorched spots, net spots, etc. are generated on the leaves.

Withering: the blade tip and the blade edge of the blade gradually lose green and yellow.

Yellowing: yellowing of stem and leaf parts.

Deformity: leaf curl, bush, swollen root, flower leaf or wrinkled leaf, etc.

In the course of calculating phytotoxicity, any of the above four characteristics is defined as phytotoxicity.

The method for calculating the occurrence proportion of the phytotoxicity comprises the following steps: the plants with phytotoxicity developed ÷ total plant number × 100%.

The three repeated phytotoxicity ratio values are averaged, and the three cucumber seedlings with 3 leaves treated by the three pesticides are found to have different phytotoxicity occurrence degrees, and the phytotoxicity occurrence rate is shown in the following table 2.

TABLE 2 phytotoxicity of ethylicin

Medicament	Percentage of phytotoxicity (%)	Description of phenomena
			30% ethylicin emulsifiable concentrate A	36.5	Severe yellowing with deformity
30% ethylicin emulsifiable concentrate B	15.4	Yellowing phenomenon is the main cause
			30% ethylicin emulsifiable concentrate C	17.8	Yellowing phenomenon is the main cause
Clean water	---	---

As can be seen from table 2, the increase in the concentration of the technical ethylicin and the decrease in the content of the impurity diethyldisulfide lead to the reduction of phytotoxicity of the formulations prepared therefrom on application to crops.