Aminofluazind and its preparation method and application

Abstract

The present invention discloses an aminofluazinam and a preparation method and application thereof, and relates to the technical field of compound synthesis. The structural formula of aminofluazinam is: The preparation method thereof comprises subjecting fluazinam and a reducing agent to an oxidation-reduction reaction in a solvent. The present invention uses fluazinam and a reducing agent as raw materials, and carries out an oxidation-reduction reaction in a solvent to obtain a metabolic impurity of fluazinam, namely, aminofluazinam. A commercial synthesis method is provided for the preparation of aminofluazinam, and the synthesized aminofluazinam can be used as an impurity reference substance for limited detection in the field of agricultural products and food, and has important practical application value in multiple fields such as food analysis and life sciences.

Description

Technical Field

[0001] The present invention relates to the technical field of compound synthesis, and in particular to aminofluazindane and a preparation method and application thereof. Background Art

[0002] Fluazifop is a dinitroaniline fungicide containing pyridinamine in its structure. It can effectively prevent and control plant diseases such as scab, anthracnose, black spot and other diseases in the production, storage and transportation of fruits and vegetables such as cabbage, tomatoes, peppers, apples and oranges; and it has a particularly outstanding preventive effect on blight, clubroot and gray mold.

[0003] At present, fluazinam is widely used worldwide due to its broad spectrum, high efficiency, low cost and easy availability. However, the abuse or irrational use of fluazinam will cause it to remain in food, posing a threat to human health. According to research reports, the toxicity of fluazinam mainly causes immune diseases, including asthma, dermatitis, etc. In order to protect consumers' food safety, many countries or authoritative organizations in the world have stipulated the maximum residue limit of fluazinam in fruits and vegetables, but there are still cases where fluazinam affects the edible safety of fruits and vegetables.

[0004] In view of this, the present invention is proposed. Summary of the invention

[0005] The object of the present invention is to provide an aminofluazinam and a preparation method and application thereof.

[0006] The present invention is achieved in that:

[0007] In a first aspect, the present invention provides an aminofluazinam, the structural formula of which is shown below:

[0008]

[0009] In a second aspect, the present invention provides a method for preparing aminofluazinam as described in the aforementioned embodiment, comprising subjecting fluazinam to a redox reaction with a reducing agent in a solvent.

[0010] In an optional embodiment, the molar ratio of fluazinam to the reducing agent is 1:1-10, preferably 1:1-5, and more preferably 1:2-5.

[0011] In an optional embodiment, the reaction temperature of the redox reaction is 25 to 80°C, preferably 35 to 80°C.

[0012] In an optional embodiment, the reaction time of the redox reaction is 1 to 72 hours, preferably 1 to 48 hours, and more preferably 1 to 2 hours.

[0013] In an optional embodiment, the reducing agent includes sodium hydrosulfide, sodium sulfide, hydrogen sulfide, hydrogen peroxide, Na2 SO 3 and FeSO 4 At least one of .

[0014] In an optional embodiment, the solvent includes at least one of pure water, methanol, acetonitrile, n-hexane and acetone.

[0015] In an optional embodiment, the redox reaction of fluazinam with a reducing agent in a solvent comprises dropwise adding a reducing agent solution into a fluazinam solution for reaction.

[0016] In an optional embodiment, the method further includes purifying the aminofluazinam obtained by the reaction.

[0017] Preferably, purification comprises separation of aminofluazinam using high performance liquid chromatography followed by removal of the solvent.

[0018] Preferably, the chromatographic conditions include: chromatographic column: Shim-pack PRC-ODS 20mmID.×250mmL.15μm; mobile phase: any one of water, acetonitrile, or a mixture of water and acetonitrile; flow rate: 0.1-10mL / min; injection volume: 0.5-10mL; wavelength: 254nm.

[0019] Preferably, removing the solvent comprises subjecting the solution collected by HPLC to rotary evaporation and then freeze drying.

[0020] In a third aspect, the present invention provides an application of aminofluazinam according to the aforementioned embodiment or aminofluazinam prepared by the preparation method according to any one of the aforementioned embodiments in the field of impurity detection.

[0021] The present invention has the following beneficial effects:

[0022] The present invention provides an aminofluazinam and a preparation method and application thereof, wherein fluazinam and a reducing agent are used as raw materials, and an oxidation-reduction reaction is performed in a solvent to obtain a metabolic impurity of fluazinam, namely, aminofluazinam. A commercial synthesis method is provided for the preparation of aminofluazinam, and the synthesized aminofluazinam can be used as an impurity reference substance for limited detection in the field of agricultural products and food, and has important practical application value in multiple fields such as food analysis and life sciences. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings required for use in the embodiments are briefly introduced below. It should be understood that the following drawings only show certain embodiments of the present invention and therefore should not be regarded as limiting the scope. For ordinary technicians in this field, other related drawings can be obtained based on these drawings without creative work.

[0024] Figure 1 The mass spectrum of aminofluazinam provided in Example 1 of the present invention. DETAILED DESCRIPTION

[0025] In order to make the purpose, technical scheme and advantages of the embodiments of the present invention clearer, the technical scheme in the embodiments of the present invention will be described clearly and completely below. If the specific conditions are not specified in the embodiments, they are carried out according to conventional conditions or conditions recommended by the manufacturer. If the manufacturer of the reagents or instruments used is not specified, they are all conventional products that can be purchased commercially.

[0026] Fluazinam is widely used around the world because it has the advantages of broad spectrum, high efficiency, low cost and easy availability, and can effectively prevent and treat plant diseases in a variety of fruits and vegetables during production, storage and transportation. However, the abuse or irrational use of fluazinam can cause it to remain in food, posing a threat to human health. Currently, many countries or authoritative agencies have set regulations on the residue limit of fluazinam in fruits and vegetables, but there are still cases where fluazinam affects the edible safety of fruits and vegetables.

[0027] Based on the above situation, in the first aspect, the present invention provides an aminofluazinam, the structural formula of which is shown below:

[0028]

[0029] After long-term research, the inventors found that fluazinam will undergo chemical transformation in the fruit and vegetable matrix and metabolize into a new pollutant, namely aminofluazinam. The residue of aminofluazinam will also affect the edible safety of fruits and vegetables, but it cannot be detected during the limit test of fluazinam. Therefore, the inventors further proposed the following solution to solve the problem that aminofluazinam cannot be detected.

[0030] In a second aspect, the present invention provides a method for preparing aminofluazinam as described in the aforementioned embodiment, comprising subjecting fluazinam to a redox reaction with a reducing agent in a solvent.

[0031] The invention uses fluazinam and a reducing agent as raw materials, performs an oxidation-reduction reaction in a solvent to obtain aminofluazinam. The preparation method is simple to operate, and the raw materials are readily available, which provides a basis for the commercial synthesis of aminofluazinam. The aminofluazinam synthesized by the method of the invention is used as an impurity reference substance, and is subjected to limited detection in the field of agricultural products and food, thereby ensuring the edible safety of fruits and vegetables.

[0032] In an optional embodiment, the molar ratio of fluazinam to the reducing agent is 1:1 to 10, preferably 1:1 to 5, and more preferably 1:2 to 5. Controlling the molar ratio of fluazinam to the reducing agent within the above range can increase the yield of aminofluazinam.

[0033] In an optional embodiment, the reaction temperature of the redox reaction is 25 to 80°C, preferably 35 to 80°C.

[0034] In an optional embodiment, the reaction time of the redox reaction is 1 to 72 hours, preferably 1 to 48 hours, and more preferably 1 to 2 hours. Increasing the temperature and extending the reaction time can increase the yield of aminofluazinam.

[0035] In an optional embodiment, the reducing agent includes sodium hydrosulfide, sodium sulfide, hydrogen sulfide, hydrogen peroxide, Na 2 SO 3 and FeSO 4 At least one of .

[0036] In an optional embodiment, the solvent includes at least one of pure water, methanol, acetonitrile, n-hexane and acetone.

[0037] In an optional embodiment, the redox reaction of fluazinam and the reducing agent in a solvent comprises dropping the reducing agent solution into the fluazinam solution for reaction. The fluazinam solution is fluazinam dissolved in any of the above solvents; the reducing agent solution is the reducing agent dissolved in any of the above solvents; and the solvent for dissolving fluazinam and the solvent for dissolving the reducing agent can be the same solvent or different solvents.

[0038] In an optional embodiment, the method further includes purifying the aminofluazinam obtained by the reaction.

[0039] Preferably, purification comprises separation of aminofluazinam using high performance liquid chromatography followed by removal of the solvent.

[0040] Preferably, the chromatographic conditions include: chromatographic column: Shim-pack PRC-ODS 20mmID.×250mmL.15μm; mobile phase: any one of water, acetonitrile, or a mixture of water and acetonitrile; flow rate: 0.1-10mL / min; injection volume: 0.5-10mL; wavelength: 254nm. By controlling the parameters of the high performance liquid chromatography method within the above range, aminofluazinam with higher purity can be obtained, providing higher detection accuracy for the limit detection of aminofluazinam.

[0041] Preferably, in order to avoid the heating self-polymerization reaction of aminofluazinam, removing the solvent comprises rotary evaporating the solution collected by high performance liquid chromatography and then freeze-drying it.

[0042] In a third aspect, the present invention provides an application of aminofluazinam according to the aforementioned embodiment or aminofluazinam prepared by the preparation method according to any one of the aforementioned embodiments in the field of impurity detection.

[0043] The features and performance of the present invention are further described in detail below in conjunction with the embodiments.

[0044] Example 1

[0045] This embodiment provides a method for preparing aminofluazinam, comprising the following steps:

[0046] S1. Redox reaction

[0047] The raw materials were weighed and dissolved in the solvent according to the molar ratio of fluazinam to sodium sulfide of 1:5, wherein fluazinam was dissolved in acetonitrile and sodium sulfide was dissolved in methanol, vortexed and mixed, and the prepared sodium sulfide solution was added dropwise to the fluazinam solution, and then stirred for 60 minutes at room temperature. After the reaction was completed, the reaction solution was concentrated to 10 mL for use.

[0048] S2. Purification

[0049] The reaction solution was placed in a high performance liquid chromatograph for separation and purification. The chromatographic conditions included: chromatographic column: Shim-pack PRC-ODS 20 mm ID.×250 mm L.15 μm; mobile phase: water / acetonitrile (2 / 8, v / v); flow rate: 4 mL / min; injection volume: 2 mL; wavelength: 254 nm.

[0050] The component with a retention time of 16 minutes was collected to obtain about 10 mL of aminofluazinam solution, which was then subjected to rotary evaporation to remove acetonitrile at room temperature and then freeze-dried to remove moisture to obtain aminofluazinam powder.

[0051] The aminofluazinam prepared in Example 1 was placed in an ultra-high performance liquid chromatography-high resolution mass spectrometer for detection, and the following Figure 1 The results are shown. Figure 1 a is the total ion current diagram of aminofluazinam provided in Example 1 of the present invention; Figure 1 b is the secondary mass spectrum of aminofluazinam provided in Example 1 of the present invention. Figure 1 It can be seen that the preparation method of aminofluazinam provided in the embodiment of the present invention can prepare aminofluazinam with higher purity.

[0052] The above are only preferred embodiments of the present invention and are not intended to limit the present invention. For those skilled in the art, the present invention may have various modifications and variations. Any modification, equivalent replacement, improvement, etc. made within the spirit and principle of the present invention shall be included in the protection scope of the present invention.

Claims

1. A method for preparing aminofluazinam, characterized in that: The structural formula of the aminofluazinam is as follows: ； The preparation method comprises subjecting fluazinam and a reducing agent to a redox reaction in a solvent; The reducing agent is sodium sulfide, and the molar ratio of fluazinam to the reducing agent is 1:1-5.

2. The preparation method according to claim 1, characterized in that: The molar ratio of fluazinam to the reducing agent is 1:2-5.

3. The preparation method according to claim 1, characterized in that: The reaction temperature of the redox reaction is 25-80°C.

4. The preparation method according to claim 1, characterized in that: The reaction temperature of the redox reaction is 35-80°C.

5. The preparation method according to claim 1, characterized in that: The reaction time of the redox reaction is 1 to 72 hours.

6. The preparation method according to claim 1, characterized in that: The reaction time of the redox reaction is 1 to 48 hours.

7. The preparation method according to claim 1, characterized in that: The reaction time of the redox reaction is 1 to 2 hours.

8. The preparation method according to claim 1, characterized in that: The solvent includes at least one of pure water, methanol, acetonitrile, n-hexane and acetone.

9. The preparation method according to claim 1, characterized in that: The redox reaction of fluazinam with a reducing agent in a solvent comprises dropping a reducing agent solution into a fluazinam solution for reaction.

10. The preparation method according to claim 1, characterized in that: The method also includes purifying the aminofluazinam obtained by the reaction.

11. The preparation method according to claim 10, characterized in that: The purification includes separating aminofluazinam using high performance liquid chromatography and then removing the solvent.

12. The preparation method according to claim 11, characterized in that: Chromatographic conditions include: chromatographic column: Shim-packPRC-ODS 20mmID.×250 mmL. 15μm; mobile phase: any one of water, acetonitrile, or a mixture of water and acetonitrile; flow rate: 0.1~10 mL / min; injection volume: 0.5~10 mL; wavelength: 254 nm.

13. The preparation method according to claim 11, characterized in that: Removal of the solvent involved rotary evaporation of the solution collected by HPLC followed by freeze drying.

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