Epioxandrolone pyrazole derivatives, their synthesis methods and applications

Abstract

The present invention belongs to the technical field of pharmaceutical synthesis, and particularly relates to epiandrosterone pyrazole derivatives, their synthesis methods and applications. The epiandrosterone pyrazole derivatives have a chemical structure represented by the general formula (1), wherein R is an alkyl group or an aromatic ring-containing group. The alkyl group is an aliphatic chain or a cycloalkane, and the aromatic ring-containing group is a phenyl group or a substituted phenyl group. The synthesis method of the epiandrosterone pyrazole derivatives uses epiandrosterone as a basic raw material and obtains the epiandrosterone pyrazole derivatives of the present invention through a series of different reactions. The epiandrosterone pyrazole derivatives disclosed in the present invention are a series of brand-new compounds, which are proposed for the first time. The synthesis method has a high preparation yield, and the obtained product is easy to separate. It is confirmed by biological assays that the epiandrosterone pyrazole derivatives exhibit good insecticidal activity against pests such as aphids, oriental armyworms, diamondback moths and whiteflies, and can be applied to the control of plant pests.

Description

Technical Field

[0001] The present invention belongs to the technical field of pharmaceutical synthesis, and particularly relates to epiandrosterone pyrazole derivatives, a synthesis method thereof, and an application thereof. Background Art

[0002] Heterocyclic compounds are a class of compounds mainly composed of five- or six-membered ring systems or fused ring systems containing one or more heteroatoms (O, N, or S). Since Anderson isolated pyrrole from bone tar in 1857, Scheele prepared furan in 1870, and Meyer discovered thiophene in 1882, it has been only over a century, and the number of heterocyclic compounds studied has developed to an astonishing amount. The number of heterocyclic compounds recorded in the Beilstein Handbook of Organic Chemistry in the 1930s of this century accounted for about 1 / 3 of the then-known hundreds of thousands of organic compounds. Among these compounds, heterocyclic compounds containing nitrogen atoms are particularly important.

[0003] Pyrazole is a class of five-membered ring aromatic heterocyclic organic compounds, which have a wide range of applications in the pharmaceutical industry. The pyrazole nucleus is one of the basic structures in many drugs, such as the antipyretic analgesic antipyrine, the free radical scavenger edaravone, and the COX-2 inhibitor celecoxib. Through continuous research, it has been found that pyrazole and its derivatives have various biological activities, such as analgesia, anti-inflammatory, antipyretic, sedative, muscle relaxation, mental excitement, anti-spasm, etc., and are low-toxic, have novel structures, and have a large space for modification, and have a wide range of applications in pesticides and medicines and are important intermediates for pesticides and medicines.

[0004] Piercing-sucking mouthpart pests are a relatively large group among garden plant pests. They are small in size, and the damage symptoms are often not obvious in the initial stage of occurrence, and are easily ignored by people. However, they are extremely numerous, often inhabiting tender branches, leaves, buds, flower buds, and fruits, sucking the plant sap, robbing its nutrients, causing the branches, leaves, and flowers to curl, and even the whole plant to wither or die. At the same time, it induces sooty mold, and sometimes the pests themselves are the vectors of virus diseases. These pests can damage most crops, causing serious losses to their yield and quality. However, after long-term use of the current effective control agents, most of them have developed relatively serious resistance to piercing-sucking mouthpart pests. The characteristics of chewing mouthpart pests damaging plants are to cause various forms of mechanical damage. For example, feeding on leaves causes notches and holes, and when severe, the mesophyll is eaten up, only the reticulate veins are left, and even all are eaten up. Therefore, there is an urgent need to screen out new control agents. Summary of the Invention

[0005] The purpose of the present invention is to overcome the shortcomings of the prior art and provide a series of new epiandrosterone pyrazole derivatives;

[0006] The second purpose of the present invention is to provide a synthesis method of epiandrosterone pyrazole derivatives.

[0007] The third object of the present invention is to provide applications of epiandrosterone pyrazole derivatives.

[0008] The purpose of the present invention is achieved by the following technical solution: the epiandrosterone pyrazole derivative has a chemical structure represented by the general formula (1):

[0009]

[0010] Wherein, R is an alkyl group or a group containing an aromatic ring, the alkyl group is an aliphatic chain or a cycloalkane, and the group containing an aromatic ring is a phenyl group or a substituted phenyl group.

[0011] Furthermore, the alkyl group is:

[0012] Furthermore, the aromatic ring-containing group is any one of (a) to (g):

[0013]

[0014] Furthermore, the epiandrosterone pyrazole derivative has the following chemical structural formula:

[0015]

[0016]

[0017] The synthesis method of epiandrosterone pyrazole derivatives, the synthesis route is:

[0018]

[0019] The reaction conditions of step a are as follows: 4-dimethylaminopyridine, triethylamine, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and compound (3) are added to dichloromethane containing compound (2), and the mixture is reacted at room temperature for 10 to 15 hours, preferably 12 hours;

[0020] The reaction conditions of step b are: using tetrahydrofuran as solvent, adding tetrabutylammonium fluoride trihydrate, and reflux reaction for 3 to 6 hours, preferably 4 hours.

[0021] Furthermore, the synthetic routes of compound (2) and compound (3) are:

[0022]

[0023] The reaction conditions of step c are as follows: compound (5) is dissolved in N,N-dimethylformamide, imidazole and tert-butyldimethylsilyl chloride are added, and the mixture is reacted at room temperature for 10 to 14 hours, preferably 12 hours;

[0024] The reaction conditions for step d are as follows: using tetrahydrofuran as the solvent, sealing, adding potassium tert-butoxide and ethyltriphenylphosphonium bromide, reacting for 50 - 70 min, preferably 60 min; dissolving compound (6) in tetrahydrofuran, adding it to the reaction system, and reacting for 22 - 26 h, preferably 24 h;

[0025] The reaction conditions for step e are as follows: using dichloromethane as the solvent, adding compound (7), water / tert-butanol (1:1), methylsulfonamide, and AD-mix-β, reacting at 0 °C for 46 - 50 h and at room temperature for 70 - 74 h; preferably reacting at 0 °C for 48 h and at room temperature for 72 h;

[0026] The reaction conditions for step f are as follows: using acetone as the solvent, adding ethyl pyrazole-4-carboxylate, potassium carbonate, and bromohydrocarbons with different substituents, reacting at 50 °C for 5 - 7 h, preferably 6 h;

[0027] The reaction conditions for step g are as follows: using ethanol as the solvent, adding sodium hydroxide, reacting at 50 °C for 5 - 7 h, preferably 6 h.

[0028] The application of the above-mentioned epiandrosterone pyrazole derivatives in plant pest control.

[0029] Furthermore, the plant pests are aphids, oriental armyworms, diamondback moths, and whiteflies.

[0030] An insecticide containing the above-mentioned epiandrosterone pyrazole derivatives.

[0031] Furthermore, the effective mass percentage content of the epiandrosterone pyrazole derivatives is 0.01% - 99.99%.

[0032] In order to apply the epiandrosterone pyrazole derivatives in the fields of agriculture and plant protection, those skilled in the art can use one or several of the epiandrosterone pyrazole derivatives as insecticidal active ingredients, in combination with a pesticidally acceptable carrier or other agricultural active ingredients, to prepare formulations convenient for application, such as water-dispersible granules, wettable powders, or dispersible oil suspensions and other dosage forms. When formulating the above different dosage forms, for those skilled in the art, in addition to using the selected bactericidal active ingredients, various auxiliaries also need to be selected, and different pesticide formulation auxiliary components (auxiliaries) can be selected according to needs. The auxiliary components can be one or several of a dispersion medium, a dispersant, an emulsifier, a wetting agent, a thickener, an antifoaming agent, an antifreezing agent, a disintegrant, a binder, a filler, etc. The formulation method of the single agent or composition formulation containing the epiandrosterone pyrazole derivatives is a conventional method in the prior art.

[0033] The present invention has the following advantages:

[0034] (1) The epiandrosterone pyrazole derivatives disclosed in the present invention are a series of brand-new compounds, which are proposed for the first time. In addition, the present invention also provides a synthesis method for the epiandrosterone pyrazole derivatives, which uses epiandrosterone as the basic raw material and obtains the epiandrosterone pyrazole derivatives of the present invention through a series of different reactions. The synthesis method has a high preparation yield, and the obtained product is easy to separate.

[0035] (2) It has been confirmed by biological assays that the epiandrosterone pyrazole derivatives exhibit good insecticidal activity against pests such as aphids, oriental armyworms, diamondback moths, and whiteflies, and can be used to prepare single-agent agricultural insecticides or mixed preparations containing the epiandrosterone pyrazole derivatives. Description of the Drawings

[0036] Figure 1 It is the single-crystal diffraction pattern of the target compound (1)-8. Detailed Embodiments

[0037] The following further describes the present invention in conjunction with the drawings and embodiments. The protection scope of the present invention is not limited to the following:

[0038] The epiandrosterone pyrazole derivative has a chemical structure represented by the general formula (1):

[0039]

[0040] Among them, R is an alkyl group or an aromatic ring-containing group. The alkyl group is a fatty chain or a cycloalkane, and the aromatic ring-containing group is a phenyl group or a substituted phenyl group.

[0041] The synthesis method of the epiandrosterone pyrazole derivative has a synthesis route as follows:

[0042]

[0043] Among them, the synthesis route of compound (2) is as follows:

[0044]

[0045] The synthesis route of compound (3) is as follows:

[0046]

[0047] The reaction reagents and conditions for each step in the above synthesis route are as follows:

[0048] Step a: Dichloromethane, EDC, DMAP;

[0049] Step b: TBAF, DMF, rt;

[0050] Step c: DMF, TBSCl, imidazole, rt;

[0051] Step d: THF, t-BuOK, EtPh3BrP;

[0052] Step e: t-BuOH, H2O, dichloromethane, Methanesulfonamide, AD-mix-β;

[0053] Step f: Acetone, K2CO3, X-R;

[0054] Step g: EtOH, H2O, NaOH, HCl.

[0055] The specific operation is as follows:

[0056] First, dissolve the epiandrosterone compound (5) in N,N-dimethylformamide, add imidazole and tert-butyldimethylchlorosilane to react to obtain compound (6); then, using tetrahydrofuran as the solvent, seal it, add potassium tert-butoxide and ethyltriphenylphosphonium bromide, and react for 1 h; dissolve compound (6) in tetrahydrofuran to react to obtain compound (7), then dissolve compound (7) in dichloromethane, add water / tert-butanol (1:1), methanesulfonamide and AD-mix-β to react to obtain compound (2); dissolve compound (8) in acetone, add potassium carbonate and bromohydrocarbons with different substituents to react to obtain compound (9), and finally, using ethanol as the solvent, add sodium hydroxide to react to obtain compound (3).

[0057] Dissolve compound (2) and compound (3) in dichloromethane, add 4-dimethylaminopyridine, triethylamine and 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride to obtain compound (4), and finally, dissolve compound (4) in tetrahydrofuran, add tetrabutylammonium fluoride trihydrate to obtain compound (1).

[0058] Example 1: The synthesis steps of epiandrosterone pyrazole derivatives are as follows:

[0059] (1) Dissolve 4.36 g of epiandrosterone (15 mmol) in N,N-dimethylformamide (60 mL), add 3.7 g of imidazole (45 mmol) and 2.71 g of tert-butyldimethylchlorosilane (18 mmol), react at room temperature for 12 h, extract with ethyl acetate and 1 mol / L hydrochloric acid aqueous solution, dry with anhydrous sodium sulfate, and concentrate under reduced pressure to obtain 5.89 g of a white solid compound (6); Add 7.42 g of ethyltriphenylphosphonium bromide (20 mmol) and 2.24 g to the reaction flask, seal it, evacuate for 1 h, dissolve 2.02 g of compound (6) (5 mmol) in tetrahydrofuran, react at room temperature for 12 h, extract with ethyl acetate and 1 mol / L hydrochloric acid aqueous solution, dry with anhydrous sodium sulfate, and concentrate under reduced pressure to obtain 7.71 g of a white solid compound (7); Add 1.42 g of methylsulfonamide (15 mmol), 7.79 g of AD-mix-β and water / tert-butanol (20 mL / 20 mL) to the reaction flask, cool in an ice bath for 10 min, dissolve 2.08 g of compound (7) (5 mmol) in 10 mL of dichloromethane, add it to the reaction flask, react in an ice bath for 48 h, react at room temperature for 72 h, then add anhydrous sodium sulfite and react for 1 h, extract with ethyl acetate, KOH (1 M) and saturated sodium chloride solution, dry with anhydrous sodium sulfate, concentrate under reduced pressure, and obtain 1.48 g of a white solid compound (2).

[0060] (2) Dissolve 0.5 g of ethyl pyrazole-4-carboxylate (3.6 mmol), bromohydrocarbon with different substituents (3.6 mmol), and 0.59 g of potassium carbonate (4.32 mmol) in acetone, add them to the reaction flask, react at 65 °C for 6 h, extract with dichloromethane and 1 mol / L hydrochloric acid aqueous solution, dry with anhydrous sodium sulfate, and concentrate under reduced pressure to obtain compound (9). Dissolve compound (9) (5 mmol) in ethanol (15 ml), add 0.42 g of sodium hydroxide (7.5 mmol), react at 50 °C for 6 h, distill under reduced pressure, add 30 mL of ice water, dropwise add 1 mol / L hydrochloric acid in an ice bath to adjust the pH to 3 - 5, precipitate will form, filter the mixture to obtain the filter residue, wash it with distilled water, and dry it to obtain compound (3).

[0061] (3) Dissolve 0.315 g of compound (2) (0.7 mmol) and compound (3) (3.5 mmol) in dichloromethane, add 0.63 g of EDCl (3.5 mmol) and 0.085 g of DMAP (0.7 mmol), react at room temperature for 12 h, extract with dichloromethane and hydrochloric acid aqueous solution (1 M), dry over anhydrous sodium sulfate, concentrate under reduced pressure to obtain compound (4); dissolve compound (4) (0.3 mmol) in tetrahydrofuran (15 mL), add 0.16 g of tetrabutylammonium fluoride trihydrate (0.6 mmol), react at room temperature for 4 h, extract with ethyl acetate and water, dry over anhydrous sodium sulfate, concentrate under reduced pressure. Purify by silica gel column chromatography (petroleum ether / ethyl acetate, 1:1, v / v) to obtain the final target compound (1).

[0062] The prepared epiandrosterone pyrazole derivatives are confirmed by 1H-NMR and 13C-NMR. Among them, the structures of compounds (1)-8 are confirmed by single crystal diffraction method, as Figure 1 shown, and the specific results are as follows:

[0063] 1. Compound (1)-1

[0064]

[0065] 1 HNMR (500 MHz, CDCl3) δ = 7.87 (d, J = 2.4 Hz, 2H), 5.26 (q, J = 6.3 Hz, 1H), 4.10 (t, J = 7.2 Hz, 2H), 3.58 (tt, J = 10.7, 4.8 Hz, 1H), 1.96 (ddd, J = 14.7, 11.5, 2.9 Hz, 1H), 1.85 (p, J = 7.4 Hz, 2H), 1.79 (dt, J = 11.6, 5.7 Hz, 2H), 1.69 (dd, J = 24.8, 12.5, 9.0, 3.7 Hz, 6H), 1.60–1.48 (m, 4H), 1.39 (d, J = 11.2, 4.3 Hz, 2H), 1.29 (t, J = 5.5 Hz, 8H), 1.25 (d, J = 14.4 Hz, 9H), 1.12 (qq, J = 11.8, 5.7 Hz, 2H), 0.95 (dd, J = 17.6, 13.4, 10.0, 4.5 Hz, 2H), 0.86 (t, J = 6.9 Hz, 3H), 0.80 (d, J = 5.7 Hz, 6H), 0.73–0.65 (m, 1H).

[0066] 1313C NMR (125 MHz, CDCl3) δ = 162.39, 140.93, 132.48, 114.90, 85.06, 75.64, 71.38, 53.96, 52.87, 51.01, 46.46, 44.96, 38.29, 37.91, 37.13, 35.59, 35.52, 32.18, 31.92, 31.62, 31.42, 30.19, 29.47, 29.29, 29.17, 28.79, 26.60, 23.41, 22.75, 20.86, 15.82, 14.88, 14.20, 12.42.

[0067] Compound (1)-2

[0068]

[0069] 1 1H NMR (500 MHz, CDCl3) δ = 7.94 (s, 1H), 7.92 (s, 1H), 7.63 (d, J = 8.2 Hz, 2H), 7.35 (d, J = 8.0 Hz, 2H), 5.38 (d, J = 7.6 Hz, 2H), 5.28 (q, J = 6.4 Hz, 1H), 3.60 (s, 1H), 1.96 (ddd, J = 14.7, 11.6, 3.0 Hz, 1H), 1.82–1.77 (m, 2H), 1.73 (t, J = 3.7 Hz, 1H), 1.70 (t, J = 4.4 Hz, 2H), 1.68 (d, J = 3.3 Hz, 1H), 1.65 (d, J = 3.5 Hz, 1H), 1.61–1.49 (m, 5H), 1.45–1.35 (m, 2H), 1.30 (d, J = 6.4 Hz, 3H), 1.28–1.27 (m, 2H), 1.14 (ddt, J = 18.3, 12.2, 6.0 Hz, 2H), 1.01–0.91 (m, 2H), 0.80 (d, J = 7.0 Hz, 6H), 0.70 (ddd, J = 12.3, 10.4, 3.9 Hz, 1H).

[0070] 1313C NMR (125 MHz, CDCl3) δ = 161.97, 141.56, 139.30, 132.89, 130.97, 128.13, 128.08, 126.06, 115.94, 84.95, 77.04, 75.81, 71.33, 55.87, 53.83, 50.91, 46.40, 44.84, 38.17, 37.80, 37.01, 35.49, 35.41, 32.08, 31.51, 31.31, 28.67, 23.30, 20.75, 15.71, 14.80, 12.32.

[0071] Compound (1)-3

[0072]

[0073] 1 1H NMR (400 MHz, CDCl3) δ = 7.92 (s, 1H), 7.91 (s, 0H), 7.87 (s, 1H), 7.40–7.33 (m, 3H), 7.31 (s, 0H), 7.29 (d, J = 3.6 Hz, 0H), 7.27–7.22 (m, 2H), 5.30 (s, 2H), 5.26 (d, J = 6.3 Hz, 1H), 3.59 (tt, J = 10.6, 4.8 Hz, 1H), 1.99–1.89 (m, 1H), 1.78 (dq, J = 11.8, 7.7, 6.4 Hz, 4H), 1.75 (s, 0H), 1.74–1.62 (m, 4H), 1.59–1.47 (m, 2H), 1.41 (ddd, J = 14.5, 11.9, 4.0 Hz, 2H), 1.28 (dd, J = 10.9, 5.5 Hz, 7H), 1.13 (qd, J = 12.0, 5.8 Hz, 2H), 1.03–0.83 (m, 2H), 0.80 (d, J = 6.9 Hz, 6H), 0.69 (dd , J = 12.4, 10.5, 4.0 Hz, 1H).

[0074] 13C NMR (100 MHz, CDCl3) δ = 162.15, 141.18, 135.19, 132.66, 129.05, 128.58, 128.03, 115.49, 84.92, 77.25, 77.05, 75.66, 71.28, 56.53, 53.82, 50.88, 46.34, 44.82, 38.14, 37.77, 36.99, 35.46, 35.38, 32.06, 31.48, 31.28, 28.66, 23.29, 20.73, 15.69, 14.76, 12.31, 0.01.

[0075] Compound (1)-4

[0076]

[0077] 1 H NMR (500 MHz, CDCl3) δ = 7.93 (d, J = 2.9 Hz, 1H), 7.89 (s, 1H), 7.33–7.25 (m, 3H), 7.12 (dd, J = 6.5, 2.1 Hz, 1H), 5.28 (d, J = 6.8 Hz, 3H), 3.59 (tt, J = 10.6, 4.7 Hz, 1H), 1.95 (ddd, J = 14.6, 11.5, 2.9 Hz, 1H), 1.79 (td, J = 11.9, 11.5, 6.8 Hz, 2H), 1.73–1.63 (m, 4H), 1.55 (dtd, J = 16.0, 12.4, 11.0, 7.7 Hz, 4H), 1.44–1.36 (m, 2H), 1.31–1.24 (m, 7H), 1.19–1.07 (m, 2H), 0.96 (ddt, J = 18.0, 10.0, 4.6 Hz, 2H), 0.80 (d, J = 6.7 Hz, 6H), 0.73–0.65 (m, 1H).

[0078] 13 C NMR (125 MHz, CDCl3) δ = 162.13, 141.54, 137.34, 135.04, 132.91, 130.43, 128.89, 128.11, 126.10, 115.91, 85.05, 75.87, 71.42, 55.92, 53.93, 51.00, 46.48, 44.93, 38.25, 37.89, 37.11, 35.58, 35.50, 32.17, 31.59, 31.40, 28.77, 23.40, 20.85, 15.81, 14.89, 12.42.

[0079] 5. Compound (1)-5

[0080]

[0081] 1 H NMR (500 MHz, MeOD) δ = 7.73 (s, 1H), 7.49 (s, 1H), 6.97 (d, J = 7.9 Hz, 2H), 6.65 (d, J = 7.9 Hz, 2H), 4.79 (s, 2H), 4.73 (q, J = 6.4 Hz, 1H), 3.02 (tt, J = 10.6, 4.8 Hz, 1H), 1.37 (t, J = 11.9 Hz, 1H), 1.33–1.11 (m, 7H), 1.11–1.05 (m, 1H), 1.04–0.98 (m, 2H), 0.90 (td, J = 11.5, 4.9 Hz, 2H), 0.76 (dd, J = 15.0, 7.9 Hz, 7H), 0.66–0.56 (m, 2H), 0.46 (tt, J = 12.2, 6.1 Hz, 2H), 0.30 (d, J = 15.2 Hz, 6H), 0.16 (ddd, J = 13.5, 10.7, 3.8 Hz, 1H).

[0082] 13 C NMR (125 MHz, MeOD) δ = 163.72, 142.29, 135.74, 134.58, 132.69, 130.32, 123.01, 116.40, 85.44, 76.40, 71.44, 56.00, 54.84, 51.47, 47.31, 45.70, 38.38, 37.80, 37.24, 36.28, 36.19, 32.92, 32.09, 31.67, 29.48, 23.96, 21.51, 15.94, 15.38, 12.68.

[0083] 6. Compound (1)-6

[0084]

[0085] 1HNMR (400 MHz, CDCl3) δ = 8.07 (s, 1H), 7.97 (s, 1H), 7.82–7.73 (m, 1H), 7.65–7.48 (m, 1H), 7.09–6.89 (m, 2H), 5.73 (d, J = 4.7 Hz, 2H), 5.28 (q, J = 6.3 Hz, 1H), 3.59 (tt, J = 10.7, 4.8 Hz, 1H), 1.97 (ddd, J = 14.5, 11.5, 2.7 Hz, 1H), 1.80 (td, J = 11.6, 7.4 Hz, 3H), 1.68 (ddd, J = 18.7, 10.7, 3.6 Hz, 4H), 1.62–1.50 (m, 4H), 1.45–1.37 (m, 2H), 1.32 (d, J = 6.4 Hz, 3H), 1.26 (d, J = 4.6 Hz, 2H), 1.17 (d, J = 6.3 Hz, 1H), 1.10 (ddd, J = 15.4, 12.1, 6.6 Hz, 2H), 0.96 (dt, J = 14.9, 10.2, 5.3 Hz, 2H), 0.80 (d, J = 2.4 Hz, 6H), 0.72–0.66 (m, 1H).

[0086] 13 CNMR (125 MHz, CDCl3) δ = 164.43, 161.58, 141.02, 138.02, 132.10, 126.85, 125.86, 119.05, 118.11, 115.55, 85.23, 76.36, 73.45, 53.28, 52.92, 50.27, (m, 1H).<e

[0087] Compound (1)-7

[0088] [[ID=e11]]

[0089] 11H NMR (500 MHz, CDCl3) δ = 7.96 (s, 1H), 7.90 (s, 1H), 7.70 (d, J = 7.7 Hz, 1H), 7.51 (t, J = 7.6 Hz, 1H), 7.43 (t, J = 7.6 Hz, 1H), 7.09 (d, J = 7.9 Hz, 1H), 5.52 (s, 2H), 5.26 (q, J = 6.2 Hz, 1H), 3.59 (tt, J = 10.9, 5.2 Hz, 1H), 1.95 (t, J = 13.0 Hz, 1H), 1.79 (dd, J = 12.5, 6.8 Hz, 2H), 1.68 (dt, J = 20.6, 7.8 Hz, 4H), 1.61–1.44 (m, 4H), 1.45–1.32 (m, 2H), 1.32–1.19 (m, 7H), 1.18–1.02 (m, 2H), 1.01–0.86 (m, 2H), 0.79 (d, J = 5.8 Hz, 6H), 0.68 (t, J = 10.3 Hz, 1H).

[0090] 13 13C NMR (125 MHz, CDCl3) δ = 162.13, 141.57, 134.04, 133.51, 132.67, 129.77, 128.58, 126.34, 115.95, 85.04, 75.91, 71.41, 53.92, 52.69, 50.99, 46.47, 44.93, 38.22, 37.87, 37.10, 35.57, 35.49, 32.16, 31.55, 31.40, 28.76, 23.40, 20.84, 15.79, 14.87, 12.41.

[0091] Compound (1)-8

[0092]

[0093] 1HNMR (400 MHz, CDCl3) δ = 7.94 (s, 1H), 7.92 (s, 1H), 7.16 (dt, J = 10.0, 8.2 Hz, 1H), 7.07 (dd, J = 10.4, 7.4, 2.2 Hz, 1H), 6.99 (dt, J = 8.1, 3.9, 1.7 Hz, 1H), 5.27 (d, J = 11.0 Hz, 3H), 3.59 (tt, J = 11.0, 4.8 Hz, 1H), 1.95 (dd, J = 14.5, 11.5, 2.8 Hz, 1H), 1.82–1.78 (m, 2H), 1.75–1.63 (m, 4H), 1.61–1.49 (m, 4H), 1.40 (qd, J = 13.0, 11.2, 3.8 Hz, 2H), 1.34–1.24 (m, 7H), 1.18–1.07 (m, 2H), 1.02–0.89 (m, 2H), 0.80 (d, J = 5.0 Hz, 6H), 0.69 (dd, J = 12.3, 10.4, 4.0 Hz, 1H).

[0094] 13 CNMR (100 MHz, CDCl3) δ = 162.07, 151.76, 149.28, 141.61, 132.84, 132.40, 124.08, 117.96, 117.12, 115.96, 84.98, 75.88, 71.32, 55.42, 53.91, 50.96, 46.46, 44.91, 38.24, 37.81, 37.09, 35.55, 35.47, 32.15, 31.56, 31.38, 28.75, 23.37, 20.82, 15.78, 14.86, 12.39.

[0095] Example 2:

[0096] The mortality rates of the epiandrosterone pyrazole derivatives listed in Table 1 against Schizaphis graminum, Brevicoryne brassicae Linn, Aphis gossypii, Aphis citricola van der Goot, and Myzus persicae were determined by the slide dipping method. Specific method: Weigh a certain amount of the compound to be tested accurately, dissolve the compound with acetone as the solvent, and prepare a solution with a concentration of 100 μg / mL using a 0.1% Tween-80 aqueous solution. Let it stand at room temperature for half an hour until the sample is completely dissolved, and then store it for later use. Paste the aphids to be tested onto a glass slide with double-sided tape, then dip the slide with the aphids into the prepared liquid medicine for 5 s and take it out, and blot the residual liquid medicine with absorbent paper. The positive control is acetamiprid, and the negative control is a 0.1% Tween-80 aqueous solution. Observe the mortality rate after moisturizing in a petri dish for 48 h, and the results are shown in Table 1.

[0097] Table 1 Mortality rates of the epiandrosterone pyrazole derivatives of formula (1) of the present invention against five kinds of aphids

[0098]

[0099] The indoor bioassay results in Table 1 show that the test compounds have good biological activities against Schizaphis graminum, Brevicoryne brassicae Linn, Aphis gossypii, Aphis citricola van der Goot, and Myzus persicae, and some compounds have similar insecticidal effects to flonicamid

[0100] Example 3:

[0101] The mortality rates of the epiandrosterone pyrazole derivatives listed in Table 2 against Mythimna separata and Plutella xylostella were determined by the leaf dipping method. Specific method: Weigh a certain amount of the compound to be tested accurately, dissolve the compound with acetone as the solvent, and prepare solutions with concentrations of 1000 μg / mL and 200 μg / mL using a 0.1% Tween-80 aqueous solution. Let it stand at room temperature for half an hour until the sample is completely dissolved, and then store it for later use. Cut the fresh wheat leaves into pieces of 0.5×0.5 cm in size, put each leaf into the prepared solution for 3 - 5 s and take it out, and wait for the solution to dry; put the 3rd instar larvae of Mythimna separata into a 24-well plate and feed them with the dried wheat leaves respectively; the positive control is abamectin, and the negative control is a 0.1% Tween-80 aqueous solution. Observe the mortality rate after 72 h, and the results are shown in Table 2.

[0102] Table 2 Mortality rates of the epiandrosterone pyrazole derivatives of formula (1) of the present invention against Mythimna separata

[0103]

[0104] Note: The concentrations of chlorfenapyr are 50 μg / mL and 10 μg / mL respectively

[0105] Table 2 The indoor bioassay results show that the tested compounds have good bioactivity against Mythimna separata, and some compounds have similar insecticidal effects to abamectin.

[0106] Example 4:

[0107] The leaf-dipping method was used to determine the toxicity of the androsterone pyrazole derivatives listed in Table 3 against Plutella xylostella. The positive control was chlorfenapyr, and the negative control was acetone. Observe the number of deaths after 72 h and calculate the corrected mortality rate. The results are shown in Table 3:

[0108] Table 3 Mortality of androsterone pyrazole derivatives of formula (1) of the present invention against Plutella xylostella

[0109]

[0110] Note: The concentrations of chlorfenapyr were 50 μg / mL and 10 μg / mL respectively

[0111] Table 3 The indoor bioassay results show that the tested compounds have good bioactivity against Plutella xylostella, and some compounds have similar insecticidal effects to chlorfenapyr.

[0112] Example 5:

[0113] The foliar spray method was used to determine the toxicity of the androsterone pyrazole derivatives listed in Table 4 against whiteflies. Specific method: Accurately weigh a certain amount of the test compound, dissolve it in acetone, and prepare solutions with concentrations of 100 and 50 μg / mL with 0.1% Tween 80 aqueous solution for standby. Spray the liquid medicine on the back of cucumber leaves, and wait for it to dry naturally. Then put the test whiteflies on the plant leaves. The positive control was thiamethoxam, and the negative control was acetone. Observe the number of deaths after 7 d and calculate the corrected mortality rate. The results are shown in Table 4.

[0114] Table 4 Mortality of androsterone pyrazole derivatives of formula (1) of the present invention against whiteflies

[0115]

[0116] Table 4 The indoor bioassay results show that the tested compounds have good bioactivity against whiteflies, and some compounds have similar insecticidal effects to thiamethoxam.

[0117] As described above, only the preferred specific embodiments of the present invention are given, but the protection scope of the present invention is not limited thereto. Any person skilled in the art within the technical scope disclosed by the present invention, according to the technical solution and inventive concept of the present invention, makes equivalent substitutions or changes, and all are covered by the protection scope of the present invention.

Claims

1. Epistosterone pyrazole derivatives, characterized in that, It has a chemical structure represented by the general formula (1): wherein, R is an alkyl group or an aromatic ring-containing group, the alkyl group is: the aromatic ring-containing group is any one of (a) to (g):

2. The epiandrosterone pyrazole derivative according to claim 1, characterized in that, the epitestosterone pyrazole derivative has the following chemical structural formula:

3. The synthesis method of the epiandrosterone pyrazole derivative according to claim 1, characterized in that, The synthesis route is: wherein, the reaction conditions for step a are: 4-dimethylaminopyridine, triethylamine, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride and compound (3) are respectively added to dichloromethane dissolving compound (2), and the reaction is carried out at room temperature for 10 - 15 h; The reaction conditions for step b are: using tetrahydrofuran as a solvent, adding tetrabutylammonium fluoride trihydrate, and refluxing for 3 - 6 h.

4. The synthetic method of the epiandrosterone pyrazole derivative according to claim 3, characterized in that, The synthesis routes of compound (2) and compound (3) are respectively: wherein, the reaction conditions for step c are: compound (5) is dissolved in N,N-dimethylformamide, imidazole and tert-butyldimethylchlorosilane are added, and the reaction is carried out at room temperature for 10 - 14 h; The reaction conditions for step d are: using tetrahydrofuran as a solvent, sealing, adding potassium tert-butoxide and ethyltriphenylphosphonium bromide, and reacting for 50 - 70 min; compound (6) is dissolved in tetrahydrofuran and added to the reaction system, and the reaction is carried out for 22 - 26 h; The reaction conditions for step e are: using dichloromethane as a solvent, adding compound (7), water / tert-butanol (1:1), methylsulfonamide and AD-mix-β, reacting at 0 °C for 46 - 50 h and at room temperature for 70 - 74 h; The reaction conditions for step f are: using acetone as a solvent, adding ethyl pyrazole-4-carboxylate, potassium carbonate and bromohydrocarbons with different substituents, and reacting at 50 °C for 5 - 7 h; The reaction conditions for step g are: using ethanol as a solvent, adding sodium hydroxide, and reacting at 50 °C for 5 - 7 h.

5. Use of the epitestosterone pyrazole derivative described in claim 1 or 2 and the epitestosterone pyrazole derivative synthesized according to claim 3 or 4 in the control of plant pests.

6. The application according to claim 5, wherein The plant pests are aphids, oriental armyworms, diamondback moths and whiteflies.

7. An insecticide, characterized in that, It contains the epitestosterone pyrazole derivative described in claim 1 or 2.

8. The insecticide according to claim 7, characterized in that, The effective mass percentage content of the epitestosterone pyrazole derivative is 0.01% - 99.99%.

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