Chiral cyano hydrazine compound, preparation method thereof and application thereof in preventing and treating aphids
By preparing chiral cyanohydrazine compounds as active ingredients in insecticides, the problems of aphid resistance and environmental stress were solved, achieving highly efficient aphid control.
Patent Information
- Application Number
- CN202610672769.0
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-05-15
- Publication Date
- 2026-08-25
AI Technical Summary
The long-term use of existing insecticides has led to increased resistance in aphids, decreased efficacy, and increased environmental pressure. There is a lack of new insecticides to effectively control aphids.
Develop chiral cyanohydrazine compounds to prepare α-hydrazine nitrile compounds with quaternary carbon chiral centers via asymmetric cyanidation reactions, which can be used as active ingredients in insecticides, especially for aphid control.
Chiral cyanohydrazine compounds exhibit excellent insecticidal activity, with some compounds showing insecticidal rates exceeding 90% and LC50 values superior to existing insecticides, providing a pioneering direction for novel resistance management.
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Abstract
Description
Technical Field
[0001] This invention belongs to the field of pesticide technology, and in particular relates to a chiral cyanohydrazine compound, its preparation method, and its application in the control of aphids. Background Technology
[0002] Aphids are a major piercing-sucking pest in agricultural production. They reproduce rapidly, have overlapping generations, and directly suck plant sap and transmit plant viruses, causing significant damage to the growth and yield of various crops, including cotton. Currently, aphid control mainly relies on chemical insecticides. However, long-term use of existing insecticides can easily lead to increased resistance, decreased efficacy, and increased environmental stress. Therefore, developing novel insecticidal lead compounds with new structural types, good activity, and potential application value is of great significance. Summary of the Invention
[0003] To address the aforementioned technical problems, this invention provides a chiral cyanohydrazine compound, its preparation method, and its application in the control of aphids.
[0004] The technical solution adopted in this invention is: a chiral cyanohydrazine compound, including hydrazine compounds with cyano-substituted chiral centers, the structure of which is shown in Formula 3;
[0005] Formula 3;
[0006] Wherein, Pg is benzoyl or halobenzoyl;
[0007] R 1 It is one of C1-C10 alkyl, aryl, and heteroaryl; wherein the heteroaryl is thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, or thiazole;
[0008] R 2 It is one of hydrogen and C1-C10 alkyl groups.
[0009] Preferably, it is as shown in any of the following structures;
[0010] 3a; 3b; 3c; 3D; 3e; 3f; 3g; 3h; 3i; 3j; 3k; 3l; 3m; 3n; 3o; 3p; 3q; 3r; 3s; 3t; 3u; 3v; 3w; 3x; 3y; 3z; 3aa; 3ab; 3ac; 3ad; 3ae; 3af; 3ag; 3ah; 3ai; 3aj; 3ak; 3al; 3am; 3an; 4a; 4b; 4c; 4d; 4e; 4f.
[0011] A method for preparing chiral cyanohydrazine compounds involves using the compound of Formula 1 as a raw material, ErCl3 as a metal catalyst, a chiral oxazoline compound as a ligand, and TMSCN as a cyanide source to carry out an asymmetric cyanation reaction of aryl or aliphatic kethydrazones in an organic solvent system to obtain the chiral cyanohydrazine compounds shown in Formula 3.
[0012] Formula 1;
[0013] Wherein, Pg is benzoyl or halobenzoyl;
[0014] R 1 It is one of C1-C10 alkyl, aryl, and heteroaryl; wherein the heteroaryl is thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, or thiazole;
[0015] R 2 It is one of hydrogen and C1-C10 alkyl groups.
[0016] Preferably, the compound shown in Formula S1 is synthesized by reacting the compound with benzoyl hydrazine;
[0017] Formula S1.
[0018] Preferably, in the reaction system, 2-10 mol% of ErCl3 and 3-15 mol% of chiral oxazoline ligands are added to the solvent and stirred for pre-complexation; then the substrate shown in Formula 1 is added, the reaction temperature is adjusted, and 3 equivalents of TMSCN and 2 equivalents of MeOH are added to carry out the asymmetric cyanation reaction.
[0019] Preferably, the solvent is one or a combination of dichloromethane, n-hexane, ethyl acetate, tetrahydrofuran, toluene, acetonitrile, DMF, DMSO, and DMA.
[0020] Preferably, the reaction temperature is -30°C. o C~60 o C; The reaction time is 0.5-48 hours.
[0021] Application of chiral cyanohydrazine compounds in insecticides.
[0022] Preferably, it is a formulation for the control of aphids.
[0023] Preferably, one or more of the following compounds are used as the active ingredient of the insecticide;
[0024] 3a; 3h; 3n; 3r; 3s; 3t; 3u; 3x; 3y; 3z; 3ad; 3ai; 3ak; 3al; 3am; 3an; 4a.
[0025] The advantages and positive effects of this invention are: it constructs a class of α-hydrazinonitrile compounds with a quaternary carbon chiral center, which can be used as active ingredients in insecticides, especially suitable for the control of aphids; through the detection of insecticidal rate and LC50 value, it was found that some of these compounds showed better insecticidal activity than deltamethrin, showing strong application potential.
[0026] This chiral molecular structure combines the three characteristics of "cyano group + chiral center + hydrazine skeleton", which is conducive to the formation of new active structure types and provides a new leading direction for the development of novel resistance control candidate insecticides. Detailed Implementation
[0027] The embodiments of the present invention will be described below.
[0028] This invention relates to a chiral cyanohydrazine compound, its preparation method, and its application in aphid control. The chiral cyanohydrazine compound possesses characteristics such as nitrogen-nitrogen bonds, cyano groups, and quaternary carbon chiral centers, making it both an important building block for chiral synthesis and a potential candidate skeleton for novel pesticide active molecules. Based on its structural properties, it can be used as an active ingredient in insecticides, particularly suitable for aphid control.
[0029] The structure of the chiral cyano compound is shown in Formula 3;
[0030] Formula 3;
[0031] Wherein, Pg is benzoyl or halobenzoyl; R 1 It is a C1-C10 alkyl, aryl, or heteroaryl group; wherein the heteroaryl group is thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, or thiazole; R 2 It is hydrogen or C1-C10 alkyl.
[0032] This chiral molecular structure combines the characteristics of a cyano group, a chiral center, and a hydrazine skeleton. Various heteroatom relay groups modify the Lewis basicity of the ligands, not only modulating the catalytic activity of the metal center but also altering the length of the pyridine nitrogen-metal bond that affects the chiral pocket of the catalyst. Furthermore, appropriately sized relay groups help create a spatially confined microenvironment, indirectly transmitting stereochemical information from the ligand's chirality to enhance enantiomeric control. PYBOX has a large phenoxy group at the C4 position of pyridine and two cisphenyl groups at the C5 positions of the two oxazoline rings. This effect allows dialkyl and alkylaryl ketone-derived propyne carbonates to provide tert-ethylamine with unprecedentedly excellent ee values.
[0033] The chiral cyanohydrazine compounds shown in Formula 3 can be prepared by asymmetric cyanation reaction of kethydrazone catalyzed by ErCl3 / chiral PYBOX ligand.
[0034]
[0035] Asymmetric cyanation of aryl or aliphatic kethydrazones was performed using ErCl3 as a metal catalyst, chiral oxazoline compounds as ligands, and TMSCN as the cyanide source to yield the target chiral α-hydrazinonitrile compound. The solvent was one or more combinations of dichloromethane, n-hexane, ethyl acetate, tetrahydrofuran, toluene, acetonitrile, DMF, DMSO, and DMA; the reaction temperature was -30°C. o C~60 oC; the reaction time is 0.5–48 hours. This preparation method is applicable to a variety of substrates, and the enantioselectivity of the product can reach up to 96%.
[0036] In some embodiments of the present invention, ErCl3 (2-10 mol%) and chiral PYBOX ligand L6 (3-15 mol%) were added to a reaction flask, and anhydrous toluene was added and stirred for pre-complexation; then hydrazone substrate was added, and after adjusting to the reaction temperature, TMSCN (3.0 equiv) and MeOH (2.0 equiv) were added, and the reaction was carried out for 4 days; after the reaction was completed, the catalyst was removed by short column and purified to obtain chiral cyanohydrazine compounds.
[0037] Different types of chiral cyano compounds can be prepared by selecting different types of kethydrazones according to the above method. In some embodiments of the present invention, the structures of the chiral cyano compounds are shown in any of the following structures.
[0038] 3a; 3b; 3c; 3D; 3e; 3f; 3g; 3h; 3i; 3j; 3k; 3l; 3m; 3n; 3o; 3p; 3q; 3r; 3s; 3t; 3u; 3v; 3w; 3x; 3y; 3z; 3aa; 3ab; 3ac; 3ad; 3ae; 3af; 3ag; 3ah; 3ai; 3aj; 3ak; 3al; 3am; 3an; 4a; 4b; 4c; 4d; 4e; 4f.
[0039] Chiral cyanohydrazine compounds can be used as active ingredients in insecticides, especially for aphid control, such as for cotton aphid (Aphis gossypii). Studies have found that various aryl-substituted chiral α-hydrazinonitrs exhibit competitive insecticidal activity against cotton aphids at 100 mg·L⁻¹. Compounds 3a, 3h, 3n, 3r, 3s, 3t, 3u, 3x, 3y, 3z, 3ad, 3ai, 3ak, 3al, 3am, 3an, and 4a all showed excellent insecticidal effects; in particular, compounds 3u, 3x, and 3ak all had insecticidal rates exceeding 90%, comparable to deltamethrin.
[0040] The present invention will now be described. Experimental methods that do not specify the operation steps are performed in accordance with the corresponding product manuals. Unless otherwise specified, the instruments, reagents and consumables used in the embodiments can be purchased from commercial companies.
[0041] Example 1: Preparation of chiral cyanonitrile compounds
[0042]
[0043] ErCl3 (0.004 mmol, 2.0 mol%) and PYBOX ligand L6 (0.006 mmol, 3.0 mol%) were added to a 5 mL screw-cap vial, followed by 2.0 mL of anhydrous toluene. The mixture was stirred at 25 °C for 2 h, and then the starting material of Formula 1 (0.2 mmol, 1.0 equivalent) was added. The mixture was cooled to -20 °C, and after 0.5 h, TMSCN (0.6 mmol, 3.0 equiv) and MeOH (0.4 mmol, 2.0 equiv) were added. The resulting mixture was stirred at -20 °C for 4 days until almost complete conversion was achieved by chromatographic analysis. The catalyst was then rapidly removed by passing the solution through a short column using ethyl acetate / CH2Cl2 as the eluent. The resulting solution was concentrated under reduced pressure, and the residue was directly purified by column chromatography using petroleum ether / ethyl acetate (10:1 ~ 3:1, v / v) as the eluent to obtain chiral cyanonitrile compounds.
[0044] The compound of Formula 1 can be purchased, synthesized using existing technology, or prepared by the following method.
[0045]
[0046] A solution of compound S1 (5.0 mmol) and benzoyl hydrazine (1.1 equiv) in ethanol (5.0 ml) was slowly added to acetic acid (10 mol %) at room temperature. The resulting mixture was stirred for 2–8 hours. The precipitate was filtered and recrystallized from ethanol to obtain the compound shown in Formula 1. In this reaction, compound S1 can be commercially available or synthesized according to existing techniques.
[0047] The structural formulas and proton NMR spectra of the chiral cyanonitrile compounds prepared according to the above method are shown in the table below.
[0048] Table 1
[0049]
[0050] Example 2: Application of chiral cyanohydrazine compounds in the control of aphids
[0051] Various chiral cyanohydrazine compounds were prepared into 10 g·L⁻¹ DMSO stock solutions, which were then diluted to 100 ppm with an aqueous solution containing 0.1% Tween 80. Cotton leaves with approximately 30–60 cotton aphids were selected and immersed in solutions containing different concentrations of chiral cyanohydrazine compounds prepared by the above method for 10 s. After being removed and dried, the leaves were placed in petri dishes containing moistened filter paper, sealed, and cultured for 24 h at 25±1℃, 70±10% relative humidity, and a light-dark ratio of 14:10. The mortality rate was then recorded.
[0052] Representative compounds such as 3a, 3h, 3n, 3r, 3s, 3t, 3u, 3x, 3y, 3z, 3ad, 3ai, 3ak, 3al, 3am, 3an, and 4a were selected for the experiment. The control group was treated with a 0.1% Tween 80 aqueous solution containing DMSO (20 mg∙L⁻¹). A separate deltamethrin (DM) group was set up to replace chiral cyanhydrazine compounds for the killing of cotton aphids under the same conditions. The results are shown in Table 2.
[0053] Table 2
[0054]
[0055] The results showed that aryl-substituted chiral cyanohydrazine compounds had good insecticidal activity against cotton aphids at 100 mg·L⁻¹, with 3u, 3x, and 3ak exhibiting the best insecticidal activity, exceeding 90%, comparable to the positive control deltamethrin.
[0056] Further studies were conducted on the insecticidal activity of compounds 3u, 3x, and 3ak to verify the insecticidal ability of chiral cyanohydrazine compounds; gradient concentration conditions were set up with concentrations of 0, 1, 5, 10, 20, 50, and 100 mg∙L⁻¹. -1 The insecticidal activity of 3U, 3X, 3AK, and the racemic mixture rac-3U at different concentrations was tested, with DM as a control. The results showed the dose-dependent insecticidal activity of various chiral cyanohydrazine compounds. The LC50 values of the chiral cyanohydrazine compounds were determined. The LC50 values of compounds 3U, 3AK, 3X, rac-3U, and deltamethrin were 15.11 mg·L⁻¹, 43.95 mg·L⁻¹, 25.99 mg·L⁻¹, and 23.99 mg·L⁻¹, respectively. Compared with the commercially available insecticide DM, compound 3U (LC50 = 15.11 mg·L⁻¹) showed the best performance. -1 ( ) has a better insecticidal effect.
[0057] The embodiments of the present invention have been described in detail above, but the content described is only a preferred embodiment of the present invention and should not be considered as limiting the scope of the present invention. All equivalent changes and improvements made within the scope of the present invention should still fall within the patent coverage of the present invention.
Claims
1. A chiral cyanohydrazine compound, characterized in that: Hydrazine compounds including chiral centers substituted with cyano groups, with structures shown in Formula 3; Formula 3; Wherein, Pg is benzoyl or halobenzoyl; R 1 It is one of C1-C10 alkyl, aryl, and heteroaryl; wherein the heteroaryl is thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, or thiazole; R 2 It is one of hydrogen and C1-C10 alkyl groups.
2. The chiral cyanohydrazine compound according to claim 1, characterized in that: As shown in any of the following structures; 3a; 3b; 3c; 3D; 3e; 3f; 3g; 3h; 3i; 3j; 3k; 3l; 3m; 3n; 3o; 3p; 3q; 3r; 3s; 3t; 3u; 3v; 3w; 3x; 3y; 3z; 3aa; 3ab; 3ac; 3ad; 3ae; 3af; 3ag; 3ah; 3ai; 3aj; 3ak; 3al; 3am; 3an; 4a; 4b; 4c; 4D; 4e; 4f.
3. A method for preparing the chiral cyanohydrazine compound according to claim 1 or 2, characterized in that: Using the compound of Formula 1 as a raw material, ErCl3 as a metal catalyst, and chiral oxazoline compounds as ligands, TMSCN as a cyanide source, aryl or aliphatic kethydrazones were subjected to asymmetric cyanidation in an organic solvent system to obtain the chiral cyanohydrazine compounds shown in Formula 3. Formula 1; Wherein, Pg is benzoyl or halobenzoyl; R 1 It is one of C1-C10 alkyl, aryl, and heteroaryl; wherein the heteroaryl is thiophene, furan, pyridine, pyrrole, pyrazole, pyrimidine, pyrazine, pyridazine, or thiazole; R 2 It is one of hydrogen and C1-C10 alkyl groups.
4. The method for preparing chiral cyanohydrazine compounds according to claim 3, characterized in that: The compound shown in Formula S1 was synthesized by reacting it with benzoyl hydrazine; Formula S1.
5. The method for preparing chiral cyanohydrazine compounds according to claim 3, characterized in that: In the reaction system, 2-10 mol% of ErCl3 and 3-15 mol% of chiral oxazoline ligands were added to the solvent and stirred for pre-complexation. Then, the substrate shown in Formula 1 was added, and after adjusting to the reaction temperature, 3 equivalents of TMSCN and 2 equivalents of MeOH were added to carry out the asymmetric cyanation reaction.
6. The method for preparing chiral cyanohydrazine compounds according to claim 5, characterized in that: The solvent is one or a combination of dichloromethane, n-hexane, ethyl acetate, tetrahydrofuran, toluene, acetonitrile, DMF, DMSO, and DMA.
7. The method for preparing chiral cyanohydrazine compounds according to any one of claims 3-6, characterized in that: The reaction temperature is -30°C o C~60 o C; The reaction time is 0.5-48 hours.
8. The use of the chiral cyanohydrazine compound as described in claim 1 or 2 in insecticides.
9. The application according to claim 8, characterized in that: A formulation for the control of aphids.
10. The application according to claim 8, characterized in that: Use one or more of the following compounds as the active ingredient in the insecticide; 3a; 3h; 3n; 3r; 3s; 3t; 3u; 3x; 3y; 3z; 3ad; 3ai; 3ak; 3al; 3am; 3an; 4a.