Preparation of all-tetra-substituted olefin compound and application of all-tetra-substituted olefin compound as nematicide

Abstract

The invention relates to a preparation method of an all-carbon-tetra-substituted olefin compound and application of the all-carbon-tetra-substituted olefin compound as a nematicide, and belongs to the technical field of forestry pest control. The compound is constructed through free radical fluorine sulfonylation reaction of FSO2Cl on allene, a multifunctional structure containing aldehyde groups, tetra-substituted olefin and allyl sulfonyl fluoride is efficiently synthesized by utilizing a bi-1, 2-carbon migration strategy, and the compound has excellent synthesis modifiability. A biological activity research shows that the compound has a remarkable killing effect on pine wood nematode and can be used for effectively preventing and treating a destructive forestry disease, namely pine wood nematode disease. According to the invention, the limitation of stereoselective synthesis of traditional tetra-substituted olefin is broken through, meanwhile, the metabolic stability and biological activity of the compound are enhanced by introducing the sulfonyl fluoride group, and an innovative solution is provided for developing a novel environment-friendly nematicide.

Description

Technical Field

[0001] The present invention relates to the field of pest control, and in particular to the application of a full-carbon tetrasubstituted olefin compound in killing nematodes in preventing and controlling forestry diseases. Background Art

[0002] Fully tetrasubstituted alkenes are important structural groups that play a key role in pharmaceuticals, natural products, and organic functional materials. Consequently, a variety of classical synthetic strategies have been developed to access tetrasubstituted alkenes, including the Wittig reaction, Horner-Wadsworth-Emmons reaction, and Peterson olefination. However, free radical methods for stereoselective construction of fully tetrasubstituted alkenes remain rare.

[0003] Compounds containing fluorinated sulfonyl (-SO2F) functional groups are widely used in chemical transformations, material synthesis, and new drug development due to their unique reactivity and biological stability. The introduction of sulfonyl fluoride groups can improve the metabolic stability, water solubility, and drug activity of drug molecules by several to dozens of times. Currently, a variety of synthetic methods for fluorosulfonylation have been developed, mainly through free radical fluorosulfonylation of alkenes or alkynes, but the fluorosulfonylation of allenes remains difficult to achieve. The present invention utilizes FSO2Cl to construct all-carbon tetrasubstituted alkenes from allenes through double 1,2 carbon migration. The generated sulfonyl fluoride has an aldehyde, a tetrasubstituted alkene, and an allylsulfonyl fluoride, and can therefore provide a variety of post-synthetic uses.

[0004] Pine wilt disease (PWD), a devastating disease of pine trees caused by the pathogenic nematode Bursaphelenchus xylophilus, is also known as the "cancer" of pine trees. Pine wilt nematodes are classified as Class I forest pests in my country, severely endangering the country's forestry economy and ecological security. Consequently, research is underway to develop chemical agents to control PWD. These agents not only kill mature pine wilt nematodes within pine trees but also poison the insects and larvae that infect them, thereby inhibiting the occurrence and spread of the disease. Summary of the Invention

[0005] The purpose of this section is to summarize some aspects of the embodiments of the present invention and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this section and the abstract and title of this application to avoid obscuring the purpose of this section, the abstract and the title of the invention, and such simplifications or omissions should not be used to limit the scope of the present invention.

[0006] In view of the above problems and / or the problems existing in the prior art, the present invention is proposed.

[0007] The present invention aims to construct a full-carbon tetrasubstituted olefin compound from allene and study its nematicidal effect in order to develop a new nematicide for preventing and controlling plant diseases.

[0008] To achieve the above object, the present invention provides a tetrasubstituted olefin compound having nematicidal properties, the structural formula of which is as follows:

[0009]

[0010] In Formula I, halogen, methoxy, methyl, cyano, tert-butyl, p-toluenesulfonyl, vinyl, carboxyl, hydroxyl, or ester-substituted aromatic groups; heterocyclic rings are thiophene, benzofuran, and indole; and R is methyl, ethyl, or ethylbenzene.

[0011] Another object of the present invention is to provide a method for preparing the above-mentioned all-carbon tetrasubstituted olefin compound, comprising adding the allene compound of formula II and fluorosulfonyl chloride (FSO2Cl) to a reaction system under visible light irradiation in a solvent to synthesize a sulfonyl fluoride olefin compound;

[0012]

[0013] In formula II, halogen, methoxy, methyl, cyano, tert-butyl, p-toluenesulfonyl, vinyl, carboxyl, hydroxyl, or ester substituted aromatic groups; heterocyclic rings include thiophene, benzofuran, and indole; R is methyl, ethyl, or ethylbenzene;

[0014] As a preferred embodiment of the present invention, the all-carbon tetrasubstituted olefin compound is prepared by further reacting an allene compound with fluorosulfonyl chloride; wherein: the solvent is selected from one or more of diethyl ether, cyclopentyl methyl ether, and methyl tert-butyl ether; the preferred solvent is diethyl ether; the light source used in the photocatalytic reaction is one or more of sunlight or 35W blue light; the reaction temperature is -20 to 30°C; and the reaction time is 2 to 6 hours;

[0015] Wherein, the molar ratio of the compound of formula II to fluorosulfonyl chloride is 1:1 to 1.2.

[0016] Furthermore, the all-carbon tetrasubstituted olefin compounds can effectively control pine wood nematodes. However, the uses of the compounds described herein are by no means limited to these genera or species, but extend to other nematodes in the same manner.

[0017] Compared with existing technologies, the present invention has the following advantages: It uses visible light-mediated electron transfer to induce fluorosulfonyl radicals, generating a sulfonyl fluoride-substituted tetra-substituted olefin compound. The synthesis method of the present invention is clean and efficient, with a short reaction time and readily available, inexpensive raw materials, facilitating large-scale production and enhanced research. Activity testing has shown that the target compound (Formula I) obtained in the present invention has an inhibitory and nematicidal effect against pine wood nematodes and other insects, and can be used as a new botanical nematicide. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 is the structural formula and yield of the all-carbon four-substituted olefin compound of the present invention;

[0019] Figure 2 This is the hydrogen spectrum of the compound prepared in Example 1 of the present invention;

[0020] Figure 3 This is the carbon spectrum of the compound prepared in Example 1 of the present invention;

[0021] Figure 4 The fluorine spectrum of the compound prepared in Example 1 of the present invention;

[0022] Figure 5 This is the hydrogen spectrum of the compound prepared in Example 2 of the present invention;

[0023] Figure 6 This is the carbon spectrum of the compound prepared in Example 2 of the present invention;

[0024] Figure 7 The fluorine spectrum of the compound prepared in Example 2 of the present invention;

[0025] Figure 8 This is the hydrogen spectrum of the compound prepared in Example 3 of the present invention;

[0026] Figure 9 This is the carbon spectrum of the compound prepared in Example 3 of the present invention;

[0027] Figure 10 The fluorine spectrum of the compound prepared in Example 3 of the present invention;

[0028] Figure 11 This is the hydrogen spectrum of the compound prepared in Example 4 of the present invention;

[0029] Figure 12 This is the carbon spectrum of the compound prepared in Example 4 of the present invention;

[0030] Figure 13 The fluorine spectrum of the compound prepared in Example 4 of the present invention;

[0031] Figure 14 This is the hydrogen spectrum of the compound prepared in Example 5 of the present invention;

[0032] Figure 15 This is the carbon spectrum of the compound prepared in Example 5 of the present invention;

[0033] Figure 16 The fluorine spectrum of the compound prepared in Example 5 of the present invention;

[0034] Figure 17 This is the hydrogen spectrum of the compound prepared in Example 6 of the present invention;

[0035] Figure 18 This is the carbon spectrum of the compound prepared in Example 6 of the present invention;

[0036] Figure 19 The fluorine spectrum of the compound prepared in Example 6 of the present invention;

[0037] Figure 20 This is the hydrogen spectrum of the compound prepared in Example 7 of the present invention;

[0038] Figure 21 The fluorine spectrum of the compound prepared in Example 7 of the present invention;

[0039] Figure 22 This is the carbon spectrum of the compound prepared in Example 7 of the present invention. DETAILED DESCRIPTION

[0040] In order to make the above-mentioned objects, features and advantages of the present invention more obvious and easy to understand, the specific implementation methods of the present invention are described in detail below in conjunction with the embodiments of the specification.

[0041] In the following description, many specific details are set forth to facilitate a full understanding of the present invention. However, the present invention may also be implemented in other ways different from those described herein. Those skilled in the art may make similar generalizations without violating the connotation of the present invention. Therefore, the present invention is not limited to the specific embodiments disclosed below.

[0042] Secondly, the term "one embodiment" or "embodiment" herein refers to a specific feature, structure, or characteristic that may be included in at least one implementation of the present invention. The phrase "in one embodiment" appearing in various places throughout this specification does not necessarily refer to the same embodiment, nor does it refer to a separate or selective embodiment that is mutually exclusive of other embodiments.

[0043] The tetrasubstituted olefin compounds of the present invention are Figure 1 shown.

[0044] Example 1

[0045] To a solution of the allene in a mixture of dioxane and ether was added FSO2Cl (0.5 mmol, 5 eq, 1 M in anhydrous trifluorotoluene). The box was made of cardboard and covered with tin foil with double-sided tape. The distance from the light source to the vial was 3.5 cm, and a fan above the box was used for cooling. After stirring at room temperature for 2 hours, the reaction was quenched with water. The reaction was quenched with water. The resulting mixture was extracted with ethyl acetate, and the combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2. The reaction process is as follows:

[0046]

[0047] The structural characterization data of the product are:

[0048] 1 H NMR (600MHz, CDCl3) δ9.44 (s, 1H), 7.48-7.42 (m, 3H), 7.30-7.27 (m, 2H,), 4.63 (d, J=4.2Hz, 2H), 2.49 (s, 3H).

[0049] 13 C NMR (150MHz, CDCl3) δ189.9, 166.8, 138.1, 123.0, 128.9, 128.6, 125.2, 47.2 (d, J=18.8Hz), 24.6.

[0050] 19 F NMR (565 MHz, CDCl3) δ 56.30.

[0051] HRMS-ESI m / z: [M+H] + Calculated for C 11 H 12 FO3S243.0486; Found 243.0474.

[0052] Example 2

[0053] To a solution of the allene in a mixture of dioxane and ether was added FSO2Cl (0.5 mmol, 5 eq, 1 M in anhydrous trifluorotoluene). The box was made of cardboard and covered with tin foil with double-sided tape. The distance from the light source to the vial was 3.5 cm, and a fan above the box was used for cooling. After stirring at room temperature for 2 hours, the reaction was quenched with water. The reaction was quenched with water. The resulting mixture was extracted with ethyl acetate, and the combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2. The reaction process is as follows:

[0054]

[0055] The structural characterization data of the product are:

[0056] 1 H NMR (600MHz, CDCl3) δ9.47 (s, 1H), 7.46 (d, J=8.2Hz, 2H), 7.22 (d, J=8.2Hz, 2H), 4.63 (d, J=4.2HZ, 2H), 2.48 (s, 3H), 1.35 (s, 9H).

[0057] 13 C NMR (100MHz, CDCl3) δ190.1, 167.0, 153.6, 135.0, 128.6, 125.8, 124.9, 47.4 (d, J=18.8Hz), 35.0, 31.3, 24.4.

[0058] 19 F NMR (565 MHz, CDCl3) δ 56.15.

[0059] HRMS-ESI m / z: [M+H] + Calculated for C 15 H 20 FO3S299.1112; Found 299.1119.

[0060] Example 3

[0061] To a solution of the allene in a mixture of dioxane and ether was added FSO2Cl (0.5 mmol, 5 eq, 1 M in anhydrous trifluorotoluene). The box was made of cardboard and covered with tin foil with double-sided tape. The distance from the light source to the vial was 3.5 cm, and a fan above the box was used for cooling. After stirring at room temperature for 2 hours, the reaction was quenched with water. The reaction was quenched with water. The resulting mixture was extracted with ethyl acetate, and the combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2. The reaction process is as follows:

[0062]

[0063] The structural characterization data of the product are:

[0064] 1 H NMR (400MHz, CDCl3) δ9.45 (s, 1H), 7.08 (s, 1H), 6.87 (s, 2H), 4.61 (s, 2H), 2.46 (s, 3H), 2.35 (s, 6H).

[0065] 13C NMR (100MHz, CDCl3) δ189.9, 166.8, 138.1, 130.0, 128.9, 128.6, 125.2, 47.2 (d, J=18.9Hz), 27.0, 24.6.

[0066] 19 F NMR (377 MHz, CDCl3) δ 56.14.

[0067] HRMS-EI m / z: [M+H] + Calculated for C 13 H 15 FO3S270.0726; Found 270.0719.

[0068] Example 4

[0069] To a solution of the allene in a mixture of dioxane and ether was added FSO2Cl (0.5 mmol, 5 eq, 1 M in anhydrous trifluorotoluene). The box was made of cardboard and covered with tin foil with double-sided tape. The distance from the light source to the vial was 3.5 cm, and a fan above the box was used for cooling. After stirring at room temperature for 2 hours, the reaction was quenched with water. The reaction was quenched with water. The resulting mixture was extracted with ethyl acetate, and the combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2. The reaction process is as follows:

[0070]

[0071] The structural characterization data of the product are:

[0072] 1 H NMR (600MHz, CDCl3) δ9.43 (s, 1H), 7.44 (d, J = 8.3Hz, 2H), 7.23 (d, J = 8.3Hz, 2H), 4.62 (d, J = 4.1Hz, 2H), 2.47 (s, 3H).

[0073] 13 C NMR (150MHz, CDCl3) δ189.3, 165.2, 136.4, 136.3, 129.9, 129.2, 125.7, 47.2 (d, J=19.1Hz), 24.5.

[0074] 19 F NMR (565 MHz, CDCl3) δ 56.54.

[0075] HRMS-ESI m / z: [M+H] + Calculated for C11 H 11 ClFO3S 277.0096Found 277.0097.

[0076] Example 5

[0077] To a solution of the allene in a mixture of dioxane and ether was added FSO2Cl (0.5 mmol, 5 eq, 1 M in anhydrous trifluorotoluene). The box was made of cardboard and covered with tin foil with double-sided tape. The distance from the light source to the vial was 3.5 cm, and a fan above the box was used for cooling. After stirring at room temperature for 2 hours, the reaction was quenched with water. The reaction was quenched with water. The resulting mixture was extracted with ethyl acetate, and the combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2. The reaction process is as follows:

[0078]

[0079] The structural characterization data of the product are:

[0080] 1 H NMR (600MHz, CDCl3) δ9.46 (s, 1H), 7.26-7.19 (m, 2H), 7.00-6.92 (m, 2H), 4.62 (d, J=4.2Hz, 2H), 3.86 (s, 3H), 2.48 (s, 3H).

[0081] 13 C NMR (150MHz, CDCl3) δ189.9, 166.2, 161.2, 130.5, 130.0, 124.5, 114.1, 55.5, 47.5 (d, J=18.5Hz), 24.2.

[0082] 19 F NMR (565 MHz, CDCl3) δ 56.60.

[0083] HRMS-ESI m / z: [M+H] + Calculated for C 12 H 14 FO4S 273.0591; Found 273.0588.

[0084] Example 6

[0085] To a solution of the allene in a mixture of dioxane and ether was added FSO2Cl (0.5 mmol, 5 eq, 1 M in anhydrous trifluorotoluene). The box was made of cardboard and covered with tin foil with double-sided tape. The distance from the light source to the vial was 3.5 cm, and a fan above the box was used for cooling. After stirring at room temperature for 2 hours, the reaction was quenched with water. The reaction was quenched with water. The resulting mixture was extracted with ethyl acetate, and the combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2. The reaction process is as follows:

[0086]

[0087] The structural characterization data of the product are:

[0088] 1 H NMR (600MHz, CDCl3) δ9.54 (s, 1H), 7.54 (d, J=8.3Hz, 2H), 7.33 (d, J=8.3Hz, 2H), 4.71 (d, J=4.0Hz, 2H), 2.57 (s, 3H).

[0089] 13 C NMR (150MHz, CDCl3) δ191.4, 168.4, 166.5, 139.3, 131.3, 130.2, 129.9, 126.5, 48.5 (d, J=18.9Hz), 25.9.

[0090] 19 F NMR (565 MHz, CDCl3) δ 57.3.

[0091] HRMS-ESI m / z: [M+Na] + Calculated for C 12 H 11 NaFO5S 309.0203; Found309.0204.

[0092] Example 7

[0093] To a solution of the allene in a mixture of dioxane and ether was added FSO2Cl (0.5 mmol, 5 eq, 1 M in anhydrous trifluorotoluene). The box was made of cardboard and covered with tin foil with double-sided tape. The distance from the light source to the vial was 3.5 cm, and a fan above the box was used for cooling. After stirring at room temperature for 2 hours, the reaction was quenched with water. The reaction was quenched with water. The resulting mixture was extracted with ethyl acetate, and the combined organic layers were dried over Na2SO4 and evaporated under reduced pressure. The residue was purified by silica gel column chromatography to obtain product 2. The reaction process is as follows:

[0094]

[0095] The structural characterization data of the product are:

[0096] 1 H NMR (600MHz, CDCl3) δ9.88 (s, 1H), 8.00 (s, 1H), 7.98-7.92 (m, 1H), 7.75 (dt, J = 7.7, 1.2Hz, 1H), 7.53 (t, J = 7.7Hz, 1H), 4.16 (s, 2H), 2.45 (s, 3H).

[0097] 13 C NMR (150MHz, CDCl3) δ190.0, 137.3, 137.0, 134.4, 133.4, 133.3, 130.2, 117.7, 117.7, 113.9, 43.9 (d, J=18.6Hz).36.9.

[0098] 19 F NMR (565 MHz, CDCl3) δ 57.66.

[0099] HRMS-ESI m / z: [M+H] + Calculated for C 12 H 11 FNO3S 268.0438; Found 268.0429.

[0100] Example 8

[0101] In order to detect the effects of all-carbon tetrasubstituted olefin compounds on pine wood nematodes, nematodes provided by the Forest Pathology Laboratory of Nanjing Forestry University were used for verification.

[0102] Prepare nematode culture medium: Pine wood nematodes were cultured with Botrytis cinerea, a fungus that has grown well on PDA medium, at 25°C in the dark. PDA medium preparation and fungal culture were performed according to conventional methods.

[0103] Prepare solvent: Methanol and 1 wt% SDS aqueous solution are mixed in proportion to prepare a solvent for later use.

[0104] Prepare a mixed sample solution: take 0.2 mg of the tetrasubstituted olefin compound prepared in Example 1 and mix it with 1 mL of the above solvent for later use.

[0105] Take 100 gL of the mixed sample solution and mix it with 100 μL of nematode culture medium, let it stand for 0.5-1 hour, and observe the nematode mortality rate; nematode mortality rate = number of dead nematodes / number of tested nematodes*100%.

[0106] The solvent was used as a blank control, that is, 100 μL of solvent was mixed with 100 μL of nematode culture medium. The number of nematodes in the nematode culture medium of the blank control group was the same as that of the experimental group. The mixture was allowed to stand for 1 hour and the results were observed.

[0107] use Figure 2 The indicated all-carbon tetrasubstituted olefin compounds were tested as insecticidal active ingredients using nematodes provided by the Forest Pathology Laboratory of Nanjing Forestry University. All pine wood nematodes were subcultured using conventional methods prior to use. The results are summarized in Table 1.

[0108] Compound number Compound concentration (μg / ml) Insecticide rate 2a 100 93％ 2b 100 40％ 2d 100 44％ 2f 100 96％ 2g 100 15％ 2j 100 80％ 2n 100 48％ 2s 100 50％ 2t 100 13％ 2u 100 71％

[0109] Table 1

[0110] The synthesis method of the present invention is clean and efficient, with a short reaction time and low energy consumption. The raw materials are cheap and easily available, which is conducive to large-scale preparation and better research. Through activity tests, the tetrasubstituted olefin compounds have strong anti-pine wood nematode activity. Related research provides a good foundation for their powerful biological activity, anticancer, antibacterial and anti-inflammatory activities.

Claims

1. A tetrasubstituted olefin compound for controlling pests, characterized in that: The structure of the compound is shown in Formula I: In Formula I, halogen, methoxy, methyl, cyano, tert-butyl, p-toluenesulfonyl, vinyl, carboxyl, hydroxyl, or ester-substituted aromatic groups; heterocyclic rings are thiophene, benzofuran, and indole; and R is methyl, ethyl, or ethylbenzene. It is prepared by reacting an allene compound with fluorosulfonyl chloride under visible light irradiation.

2. The allene compound according to claim 1, wherein: Its structure is shown in Formula II: In formula II, the aromatic group is substituted by halogen, methoxy, methyl, cyano, tert-butyl, p-toluenesulfonyl, vinyl, carboxyl, hydroxyl, or ester; the heterocyclic ring includes thiophene, benzofuran, and indole; and R is methyl, ethyl, or ethylbenzene.

3. The method for preparing a tetrasubstituted olefin compound according to claim 1, wherein the tetrasubstituted olefin compound is prepared by further reacting an allene compound with fluorosulfonyl chloride (FSO2Cl) under visible light irradiation; wherein: The solvent is selected from one or more of diethyl ether, cyclopentyl methyl ether, and methyl tert-butyl ether; preferably, the solvent is diethyl ether; the light source used in the photocatalytic reaction is one or more of sunlight or 35W blue light; the reaction temperature is -20 to 30°C; and the reaction time is 2 to 6 hours; Wherein, the molar ratio of the compound of formula II to fluorosulfonyl chloride is 1:1 to 1.

2.

4. The tetrasubstituted olefin compound according to claim 1, characterized in that: The tetrasubstituted olefin compound is used in preventing and controlling forest pests and diseases, especially in preventing and controlling nematode diseases.

5. The use according to claim 4, characterized in that Controlling forest pests and diseases refers to preventing or making the development or growth of forest pests more difficult, thereby reducing infection pressure, keeping plants healthier, and reducing damage caused by nematodes; plant nematodes include plant-parasitic nematodes and soil-dwelling nematodes, such as pine wood nematodes (Bursaphelenchus xylophilus), which are effectively controlled by the compounds described herein; however, the uses of the compounds described herein are by no means limited to these genera or species, but extend to other nematodes in the same manner.

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