Thiocarbamic acid selenotrithioester derivatives and preparation method and application thereof

Abstract

The invention relates to the technical field of chemical pesticides, and discloses thiocarbamate selenotrithioate derivatives and preparation methods and applications thereof, wherein the structural formula of the derivatives is structure I and / or structure II; the structure I is:; the structure II is:. The thiocarbamate selenotrithioate derivatives obtained in the invention have good antibacterial activity.

Description

Technical Field

[0001] The invention relates to the technical field of chemical pesticides, and in particular to selenothiocarbamate trithioester derivatives and preparation methods and applications thereof. Background Art

[0002] Organic selenium chemistry is an important developing field. It has similarities with organic sulfur chemistry, but also has its own characteristics: selenium can neutralize or transform free radicals, has antioxidant properties, and active selenides can directly act on viruses, inhibiting their replication in the body. It can also participate in cell repair and prevent a variety of viral invasions. It has broad application prospects and has become a hot spot for research and development among scholars at home and abroad.

[0003] Thiram and disulfiram are the first tetrasubstituted thiuram disulfide fungicides discovered by scientists. They are mainly used to treat seeds and soil, and to prevent and control powdery mildew, smut, and damping-off of rice seedlings in cereal crops. They can also be used for some fruit trees and vegetable diseases. In other fields, such compounds can also be used as promoters for rubber adhesives, lubricant additives, antibacterial agents and deodorants for soaps. Disulfiram was once used as a drug for alcohol abstinence in medicine. Therefore, such structures have good biological activity. We hope to further explore the application potential of such structures in pesticides based on existing research and develop more efficient new agricultural antibacterial agents.

[0004] In the prior art, the products obtained by introducing selenium into structures such as tetrasubstituted thiuram disulfide are relatively few, so its potential needs to be further explored. Summary of the invention

[0005] In order to solve the above technical problems, the present invention provides selenothiocarbamate trithioester derivatives and preparation methods and applications thereof. The selenothiocarbamate trithioester derivatives obtained in the present invention have good antibacterial activity.

[0006] The present invention provides selenothiocarbamate trithioester derivatives, wherein the structural formula of the derivatives is structure I and / or structure II:

[0007] The structure I is:

[0008] ;

[0009] The structure II is:

[0010] .

[0011] The present invention also provides a method for preparing the selenotrithiocarbamate derivatives, which comprises:

[0012] Add reactants and drop carbon disulfide in N,N-dimethylformamide aqueous solution, mix well, then drop carbon tetrabromide, separate solid and liquid, and obtain intermediate product; add intermediate product to organic reagent, add selenium powder, sodium tungstate, drop hydrogen peroxide in sequence, react, precipitate solid, and separate solid and liquid.

[0013] Furthermore, the reactant is pyrrolidine or 3-methylpiperidine.

[0014] Furthermore, the organic reagent includes one or more of methanol, ethanol, water, acetonitrile, acetone, acetic acid, and N,N-dimethylformamide.

[0015] Furthermore, the preparation method of the N,N-dimethylformamide aqueous solution is as follows: N,N-dimethylformamide is mixed with deionized water, and the volume ratio of N,N-dimethylformamide to deionized water is 1:1.

[0016] Furthermore, the molar concentration of the reactant in the N,N-dimethylformamide aqueous solution is 0.1 mol / 300 mL.

[0017] Furthermore, the molar concentration of carbon disulfide in the N,N-dimethylformamide aqueous solution is 0.1 mol / 300 mL.

[0018] Furthermore, the mixing method can be stirring, and the stirring time can be adjusted by those skilled in the art according to actual needs. As an example, in the present invention, the stirring time is 10 min-15 min.

[0019] Furthermore, the molar concentration of carbon tetrabromide in the N,N-dimethylformamide aqueous solution is 0.1 mol / 300 mL.

[0020] Furthermore, after the carbon tetrabromide is added dropwise, stirring may be performed. The stirring is to promote sufficient reaction. Those skilled in the art may adjust the stirring time according to actual conditions. As an example, the stirring time is 1 hour.

[0021] Furthermore, when carbon disulfide and carbon tetrabromide are added dropwise, the temperature of the solution to be added is maintained at 0°C.

[0022] Furthermore, the added mass of the organic reagent is 3-5 times that of the intermediate product.

[0023] Furthermore, the molar ratio of the selenium powder to the reactant is 1:2.

[0024] Furthermore, the molar ratio of the selenium powder, hydrogen peroxide and sodium tungstate is 1000:100:1.

[0025] Furthermore, the reaction time is 50 min-70 min.

[0026] Furthermore, the method for precipitating the solid is by adding deionized water.

[0027] In the present invention, after the reaction is complete, the product has a certain solubility in the system. After adding deionized water, the product becomes insoluble and is precipitated.

[0028] Furthermore, when the hydrogen peroxide solution was added dropwise and the reaction was carried out, the temperature was maintained at 0°C.

[0029] The present invention also discloses the application of the selenotrithiothioate derivatives of thiocarbamate in plant protection, in agriculture for preventing and controlling plant fungal diseases, and in pesticide compositions.

[0030] Furthermore, in the application, it is also necessary to add Baochan brand Kangquan 808.

[0031] Furthermore, the mass ratio of the selenothiocarbamate trithioester derivative to Baochan Kangquan 808 is 1:1.

[0032] Furthermore, in the application, cedarwood triene glycol (ODE286), 5-ethoxymethylfurfural (EM-05), organic bentonite and methyl oleate are also added.

[0033] Furthermore, the specific method of the application includes: 10g of thiocarbamate selenotrithioate derivatives, 10g of Baochan brand Kangquan 808, 13g of cedartriene glycol (ODE286), 2.5g of 5-ethoxymethylfurfural (EM-05), 0.2g of organic bentonite, and 64.3g of methyl oleate. After shearing evenly, zirconium beads are added in a mass ratio of 1:1.4, and sand milled for 2 hours.

[0034] The embodiments of the present invention have the following technical effects:

[0035] 1. The selenothiocarbamate trithioester compounds obtained by the present invention have good inhibitory activity against fungi, can be used as fungicides in agriculture, and can achieve good antibacterial effects, and have important application prospects.

[0036] 2. The method for preparing the compound of the present invention has simple synthesis operation, high yield and good product purity.

[0037] 3. In the present invention, and These two groups have a great effect on the stability of the structure. The groups have a more rigid structure, which increases the melting point of the product and makes it more stable, thus having better bactericidal activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0038] In order to more clearly illustrate the specific implementation methods of the present invention or the technical solutions in the prior art, the drawings required for use in the specific implementation methods or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are some implementation methods of the present invention. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0039] Figure 1 It is a structural schematic diagram provided by Example 1 of the present invention.

[0040] Figure 2 This is the data result of Example 1 of the present invention for inhibiting tobacco bacterial wilt pathogen.

[0041] Figure 3 This is the test of Example 1 of the present invention on pitaya branches with ulcer disease, wherein Figure 3 (a) shows the state of the dragon fruit branches before spraying Example 1. Figure 3 (b) shows the state of the dragon fruit branches three days after spraying Example 1. Figure 3 (c) shows the state of the dragon fruit branches six days after spraying Example 1. Figure 3 Middle (d) shows the state of the pitaya branches fourteen days after spraying Example 1. DETAILED DESCRIPTION

[0042] In order to make the purpose, technical solution and advantages of the present invention clearer, the technical solution of the present invention will be described clearly and completely below. Obviously, the described embodiments are only part of the embodiments of the present invention, not all of the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by ordinary technicians in this field without creative work belong to the scope of protection of the present invention.

[0043] In a first aspect, some embodiments of the present invention provide selenothiocarbamate trithioester derivatives, wherein the derivatives have the structural formula of structure I and / or structure II:

[0044] The structure I is:

[0045] ;

[0046] The structure II is:

[0047] .

[0048] In the two substances of the present invention and The two groups have a greater stability on the structure. The groups have a more rigid structure, which increases the melting point of the product and makes it more stable, thus having better bactericidal activity.

[0049] In a second aspect, some embodiments of the present invention also provide a method for preparing the selenothiocarbamate trithioester derivatives, the preparation method comprising:

[0050] Add reactants and drop carbon disulfide in N,N-dimethylformamide aqueous solution, mix well, then drop carbon tetrabromide, separate solid and liquid, and obtain intermediate product; add intermediate product to organic reagent, add selenium powder, sodium tungstate, drop hydrogen peroxide in sequence, react, precipitate solid, and separate solid and liquid.

[0051] In some embodiments, the reactant is pyrrolidine or 3-methylpiperidine.

[0052] In some embodiments, the organic reagent includes one or more of methanol, ethanol, water, acetonitrile, acetone, acetic acid, and N,N-dimethylformamide.

[0053] In some embodiments, the N,N-dimethylformamide aqueous solution is prepared by mixing N,N-dimethylformamide with deionized water, wherein the volume ratio of N,N-dimethylformamide to deionized water is 1:1.

[0054] In some embodiments, the molar concentration of the reactant in the N,N-dimethylformamide aqueous solution is 0.1 mol / 300 mL.

[0055] In some embodiments, the molar concentration of carbon disulfide in the N,N-dimethylformamide aqueous solution is 0.1 mol / 300 mL.

[0056] In some embodiments, the molar concentration of carbon tetrabromide in the N,N-dimethylformamide aqueous solution is 0.1 mol / 300 mL.

[0057] In some embodiments, when carbon disulfide and carbon tetrabromide are added dropwise, the temperature of the solution to be added is maintained at 0°C.

[0058] In the present invention, carbon tetrabromide is added dropwise for reaction, and the reactant produced is insoluble in the system and is therefore precipitated. In addition, the temperature is controlled during the reaction because the reaction is exothermic, which may cause temperature rise and impurity generation.

[0059] In some embodiments, the added mass of the organic reagent is 3-5 times that of the intermediate product.

[0060] In some embodiments, the molar ratio of the selenium powder to the reactant is 1:2.

[0061] In some embodiments, the molar ratio of the selenium powder, hydrogen peroxide and sodium tungstate is 1000:100:1.

[0062] In some embodiments, the reaction time is 50 min-70 min.

[0063] In some embodiments, the method of precipitating the solid is by adding deionized water.

[0064] In some embodiments, the temperature is maintained at 0° C. during the dropwise addition of hydrogen peroxide and the reaction.

[0065] In a third aspect, some embodiments of the present invention also provide applications of selenothiocarbamate trithioester derivatives in plant protection, in agriculture for controlling plant fungal diseases, and in pesticide compositions.

[0066] In some embodiments, during the application, it is also necessary to add Baochan Kangquan 808.

[0067] In some embodiments, the mass ratio of the selenothiocarbamate trithioester derivative to Baochan Kangquan 808 is 1:1.

[0068] The following is described in conjunction with specific embodiments:

[0069] Embodiment 1

[0070] In a 1-liter four-necked flask, add 150 mL of N,N-dimethylformamide, 150 mL of deionized water, and pyrrolidine (7.11 g, 0.1 mol), and then add carbon disulfide (7.61 g, 0.1 mol) dropwise at 0°C. Stir for 10 minutes after the addition. Add carbon tetrabromide (33.16 g, 0.1 mol) dropwise at 0°C. Stir the precipitated solid for 1 hour and filter with suction to obtain 14.6 g of 1,1′-(dithiocarbonyl disulfide)bispyrrole.

[0071] 14.6 g of the above-obtained 1,1′-(dithiocarbonyl disulfide)bispyrrole was added to 50 ml of acetonitrile, and selenium powder (3.95 g, 0.05 mol) and sodium tungstate (1.47 g, 5 mmol) were added dropwise at 0°C. After the addition was completed, the reaction was maintained at 0°C for 1 hour. Water was added to precipitate a solid, and 15.88 g of the product of structure I was obtained by suction filtration. Figure 1 As shown, the yield is 85.5%.

[0072] NMR data of Example 1: 1 H NMR (400 MHz, CDCl3) δ 3.97 (s, 1H, -NC H 2), 3.75(s, 1H, -NC H 2), 2.09 (t, J = 28.8 Hz, 2H, C H2). 13 C NMR (101 MHz, CDCl3) δ189.23, 56.97, 51.00, 26.61, 24.27. 77 Se NMR (76 MHz, CDCl3) δ 462.85. HRMS(ESI) Calcd. for C 10 H 16 N2S4SeNa + [M+H] + 394.9259, Found 394.9256.

[0073] Embodiment 2

[0074] In a 1-liter four-necked flask, add 150 mL of N,N-dimethylformamide, 150 mL of deionized water, and 3-methylpiperidine (9.92 g, 0.1 mol), and then add carbon disulfide (7.61 g, 0.1 mol) dropwise at 0°C. Stir for 10 minutes after the addition. Add carbon tetrabromide (33.16 g, 0.1 mol) dropwise at 0°C. Stir the precipitated solid for 1 hour and filter with suction to obtain 17.4 g of 1,1′-(dithiocarbonyl disulfide)bis-3-methylpiperidine.

[0075] To 17.4 g of the above-obtained 1,1′-(dithiocarbonyl disulfide)bis-3-methylpiperidine was added selenium powder (3.95 g, 0.05 mol) and sodium tungstate (1.47 g, 5 mmol) in 55 ml of acetonitrile, and hydrogen peroxide (1.70 g, 0.05 mmol) was added dropwise at 0°C. After the addition was complete, the temperature was maintained at 0°C for 1 hour, and water was added to precipitate a solid. The product of structure II was obtained by suction filtration to obtain 17 g, with a yield of 79.5%.

[0076] NMR data of Example 2: 1 H NMR (600 MHz, CDCl3) δ 4.69 (dd, J = 34.6, 11.6Hz, 2H), 3.16 (t, J = 11.8 Hz, 1H), 2.84 (t, J = 11.8 Hz, 1H), 1.94 – 1.72(m, 4H), 1.28 – 1.21 (m, 1H), 0.97 (d, J = 6.5 Hz, 3H).

[0077] Comparative Example 1: Thiophanate-methyl.

[0078] Comparative Example 2: Copper King.

[0079] Comparative Example 3:

[0080] In a 1L four-necked flask, add 150mL N,N-dimethylformamide, 150mL deionized water, and diethylamine (7.31g, 0.1mol), and add carbon disulfide (7.61g, 0.1mol) dropwise at 0°C. Stir for 10 minutes after the addition. Add carbon tetrabromide (33.16g, 0.1mol) dropwise at 0°C. Stir the precipitated solid for 1 hour and filter to obtain 14.8g of tetraethylthiuram disulfide.

[0081] 14.8 g of tetraethylthiuram disulfide obtained above was added to 45 ml of acetonitrile, selenium powder (3.95 g, 0.05 mol) and sodium tungstate (1.47 g, 5 mmol), and hydrogen peroxide (1.70 g, 0.05 mmol) was added dropwise at 0°C. After the addition was completed, the reaction was maintained at 0°C for 1 hour, water was added, and the solid was precipitated. The product of Comparative Example 3 was obtained by suction filtration. 11.51 g, with a yield of 61.3%.

[0082] NMR data of comparative example 3: 1 H NMR (400 MHz, CDCl3) δ 3.86 (q, J = 7.2 Hz, 2H), 1.33 (t, J = 7.1 Hz, 3H). 13 C NMR (101 MHz, CDCl3, ppm) δ 194.15, 48.08,12.17. 77 Se NMR (76 MHz, CDCl3) δ 418.23.

[0083] The products obtained from the above examples and comparative examples were tested:

[0084] (1) The in vitro antibacterial activity of the Examples and Comparative Examples against common crop-harmful fungi was tested by agar dilution method:

[0085] Test method: Dissolve the test agent in dimethyl sulfoxide (DMSO) and dilute it with 1‰ Tween water to a concentration of 500mg / L. Take 1mL and inject it into a sterilized culture dish, then add 9mL PDA culture medium (commercially available) to make a drug-containing plate with a final concentration of 50mg / L. The pathogen to be tested is inoculated on the PDA culture medium and cultured for 7 days. After that, a 4mm diameter bacterial cake is cut from the edge of the colony with a hole puncher and inoculated into the drug-containing plate. Three pieces per dish are placed in an equilateral triangle, and no drug is added as a blank control. After each test group is cultured in a 24±1℃ incubator for 48~72h, the hyphae expansion diameter is measured by the cross method and the average value is taken. Compared with the control group, the relative inhibition percentage of the sample is calculated;

[0086] Relative inhibition rate (%) = (colony diameter of control group - colony diameter of treatment group) ÷ colony diameter of control group × 100;

[0087] The tested bacteria species are Alternaria solani, Fusarium graminearum, Magnaporthe grisea, Phytophthora capsica, Sclerotinia sclerotiorum, Botrytis cinerea, Thanatephoruscucumeris. The test results of the embodiment are compared with those of the thiophanate-methyl standard, and the test concentrations of the embodiment and the comparative example are both 50 μg / mL.

[0088] (2) The antibacterial effect of the embodiments and comparative examples on citrus canker bacteria was tested:

[0089] Example 1 and Comparative Example 2 were used to treat a suspension of citrus canker bacteria, and the test environment was 27° C. The mass concentration of Comparative Example 2 was 1.4 g / L, and the mass concentration of Example 1 was 0.5 g / L.

[0090] (3) Example 1 is used to treat ulcer disease.

[0091] Results and Analysis:

[0092] Table 1 In vitro antibacterial performance test results of the embodiments and comparative examples

[0093] — Tomato early blight(%) Wheat Gibberella(%) Rice blast (%) Phytophthora capsici(%) Rapeseed sclerotium (%) Cucumber gray mold (%) Rice sheath blight (%) Example 1 68.4 65.6 100.0 94.4 98.5 100.0 100.0 Example 2 57.9 40.6 88.2 36.1 89.4 78.8 93.7 Comparative Example 1 73.9 73.1 76.0 82.6 96.4 96.1 96.1 Comparative Example 3 15.8 3.1 17.6 27.8 22.7 30.3 49.2

[0094] Table 2 Test results of the antibacterial effect of the examples and comparative examples on citrus canker bacteria

[0095] Drug number <![CDATA[OD before incubation 600 > <![CDATA[OD after incubation 600 > <![CDATA[OD 600 Added value]]> Example 1 1.983 1.160 -0.823 Comparative Example 2 2.106 0.106 -2.000

[0096] As can be seen from the results in Table 1, the preliminary screening results of the antibacterial activity experiment of selenothiocarbamate trisulfide compounds show that this type of compound has good antibacterial activity. In particular, it has a very good inhibitory effect on rice blast, rape sclerotia, and rice sheath blight. Some selenothiocarbamate asymmetric disulfide compounds also have outstanding inhibitory effects on other plant fungi.

[0097] It can be found in Table 2 that the embodiments of the present invention have a good antibacterial effect on citrus canker bacteria.

[0098] Example 1 was dissolved in dimethyl sulfoxide to prepare solutions of different concentrations for inhibiting tobacco bacterial wilt pathogens, such as Figure 2 As shown, the initial OD 600 It can be found that when Example 1 has good antibacterial ability, when its concentration reaches 10 μg / mL, it has achieved a good antibacterial effect.

[0099] Example 1 was dissolved in dimethyl sulfoxide to prepare a concentration of 2 mg / L, and sprayed on pitaya branches with ulcer disease. Before use, the ulcer disease of the branches was serious. After three days, the ulcer disease stopped worsening and scabs began to form. After six days, the scab formation effect was obvious. After fourteen days, the ulcer was completely controlled and the surrounding area of ​​the affected area did not expand. The embodiment has a significant therapeutic effect in preventing and treating ulcer disease on pitaya branches, and effectively protects the growth of the fruit during the development of pitaya fruit. Figure 3 shown.

[0100] Finally, it should be noted that the above embodiments are only used to illustrate the technical solutions of the present invention, rather than to limit it. Although the present invention has been described in detail with reference to the aforementioned embodiments, those skilled in the art should understand that they can still modify the technical solutions described in the aforementioned embodiments, or replace some or all of the technical features therein by equivalents. However, these modifications or replacements do not deviate the essence of the corresponding technical solutions from the technical solutions of the embodiments of the present invention.

Claims

1. Thiocarbamic acid selenotrithioester derivatives, characterized in that: The structural formula of the derivative is structure I or structure II: The structure I is: ； The structure II is: 。 2. The method for preparing the selenothiocarbamate trithioester derivatives according to claim 1, characterized in that: The preparation method comprises: Add the reactants and carbon disulfide dropwise to the N,N-dimethylformamide aqueous solution, mix well, then drop carbon tetrabromide, separate the solid and liquid, and obtain the intermediate product; add the intermediate product to the organic reagent, add selenium powder, sodium tungstate, drop hydrogen peroxide, react, precipitate solid, and separate the solid and liquid; The reactant is pyrrolidine or 3-methylpiperidine; The organic reagent is selected from one or more of methanol, ethanol, water, acetonitrile, acetone, acetic acid, and N,N-dimethylformamide.

3. The preparation method according to claim 2, characterized in that: The molar concentration of the reactant in the N,N-dimethylformamide aqueous solution is 0.1 mol / 300 mL; The molar concentration of carbon disulfide in the N,N-dimethylformamide aqueous solution is 0.1 mol / 300 mL; The molar concentration of carbon tetrabromide in the N,N-dimethylformamide aqueous solution is 0.1 mol / 300 mL.

4. The preparation method according to claim 2, characterized in that: When adding carbon disulfide and carbon tetrabromide, keep the temperature of the solution being added at 0°C; During the dropwise addition of hydrogen peroxide and the reaction, the temperature was maintained at 0°C.

5. The preparation method according to claim 2, characterized in that: The added mass of the organic reagent is 3-5 times that of the intermediate product; The molar ratio of the selenium powder to the reactant is 1:2; The molar ratio of the selenium powder, hydrogen peroxide and sodium tungstate is 1000:100:

1.

6. The preparation method according to claim 2, characterized in that: The reaction time is 50 min-70 min.

7. The preparation method according to claim 2, characterized in that: The method for precipitating the solid is by adding deionized water.

8. Use of the selenotrithiothioate derivatives of thiocarbamate according to claim 1 or the selenotrithiothioate derivatives of thiocarbamate obtained by the preparation method according to any one of claims 2 to 7 in preventing and controlling plant fungal diseases.

9. Use of the selenotrithioester derivatives of thiocarbamate according to claim 1 or the selenotrithioester derivatives of thiocarbamate obtained by the preparation method according to any one of claims 2 to 7 in the preparation of pesticide compositions.

10. The use according to claim 9, characterized in that: It is also necessary to add Baochan brand Kangquan 808; the mass ratio of the thiocarbamate selenotrithioester derivative to Baochan brand Kangquan 808 is 1:1.

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