Mandelonitrile alcohol ester compound and application thereof

Abstract

The invention relates to application of a mandelonitrile alcohol ester compound. Specifically, the invention discloses a compound with a structure as shown in a formula (A) or a pharmaceutically acceptable salt thereof, and the compound in the formula (A) is shown in the specification for details. The compound has the advantages of high fatality rate and high knockdown speed on pests such as mosquitoes and flies.

Description

Technical Field

[0001] The present invention belongs to the field of pesticides and specifically relates to a mandelonitrile alcohol ester compound and application thereof. Background Art

[0002] At present, the main pesticides used to control mosquitoes are organochlorine, organophosphorus, carbamate and pyrethroid pesticides. However, due to long-term, large-scale and irrational use, mosquitoes have developed resistance to these pesticides, and the resistance level is still rising. As a result, the use of these pesticides has continued to increase, and the toxicity to non-target organisms and the pressure on the environment have also increased. Summary of the invention

[0003] The primary purpose of the present invention is to provide a mandelonitrile alcohol ester compound and application thereof.

[0004] To achieve the above purpose, the present invention adopts the following technical solution:

[0005] A mandelonitrile alcohol ester compound, the compound is a compound represented by formula (A) and a pharmaceutically acceptable salt thereof,

[0006]

[0007] In the formula,

[0008] R1 can be selected from hydrogen, C 1-6 Alkyl, substituted or unsubstituted C 6-12 Aryl, substituted or unsubstituted C 5-12 Heteroaryl; wherein the substituted refers to being substituted by one or more substituents selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl;

[0009] R2 can be selected from hydrogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or halogenated C 1-6 Alkoxy.

[0010] R3 can be selected from substituted or unsubstituted C 6-12 Aryl; wherein the substituted refers to being substituted by one or more substituents selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl;

[0011] R4 can be selected from hydrogen, C 1-6 alkyl.

[0012] In the formula, the cross connecting R1, R2, and R4 represents a double bond, and the double bond configuration can be Z configuration or E configuration. The cross double bonds appearing in other structural formulas in this text also represent that the configuration at that location can be Z or E.

[0013] Preferably, the compound is a compound represented by formula (A) and a pharmaceutically acceptable salt thereof, wherein:

[0014] R1 is hydrogen, C 1-3 Alkyl, substituted or unsubstituted C 6-8 Aryl, substituted or unsubstituted C 5-8 Heteroaryl; wherein the substituted refers to being substituted by one or more substituents selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl;

[0015] R2 is hydrogen, C 1-3 Alkyl, halogenated C 1-3 Alkyl, halogenated C 1-3 Alkoxy;

[0016] R3 is substituted or unsubstituted C 6-8 Aryl; wherein the substituted refers to being substituted by one or more substituents selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, carboxyl, nitro, C 1-3 Alkyl, halogenated C 1-3 Alkyl, C 1-3 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl.

[0017] R4 is hydrogen, C 1-3 alkyl;

[0018] Further preferably, the compound is the following compound and a pharmaceutically acceptable salt thereof,

[0019]

[0020]

[0021]

[0022] The synthesis route of the compound of general formula (A) of the present invention is shown below:

[0023]

[0024] wherein the substituents R1, R2, R3 and R4 are as defined above.

[0025] The base is one or more of sodium carbonate, sodium bicarbonate, potassium carbonate, cesium carbonate, potassium phosphate, sodium acetate, potassium acetate, triethylamine, isopropylamine and pyridine.

[0026] The reaction temperature is 25°C.

[0027] The reaction solvent is one of N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile, pyridine, tetrahydrofuran, 1,4-dioxane, acetone, dichloromethane, 1,2-dichloroethane, or a mixed solvent of two or more thereof.

[0028] Reaction time is 10 minutes to 6 hours

[0029] The synthesis steps of the specific embodiment are as follows:

[0030] Add 100 mL of the above solvent to a 250 mL four-necked flask with mechanical stirring, add 12 mmol of α-nitrile alcohol b, start stirring, and then add 15 mmol of the above base. After cooling to 0°C, slowly add 10 mmol of the above acyl chloride a, and then react at room temperature for 10 minutes to 6 hours. After the reaction is completed, add 20 mL of water and continue stirring for 30 minutes, then stop stirring and let stand for 15 minutes, transfer to a 250 mL separatory funnel, take the organic phase and remove the solvent by rotary evaporation at 25°C, and the obtained residue is dissolved in dichloromethane, separated and purified by column chromatography (petroleum ether: ethyl acetate) to obtain mandelonitrile alcohol ester compounds.

[0031] A pesticide composition, comprising the compound represented by formula (A) and a pharmaceutically acceptable salt thereof.

[0032] One application is the application of the compound represented by formula (A) and its pharmaceutically acceptable salt or the pesticide composition in controlling and eliminating sanitary pests.

[0033] That is, the compound of formula (A) or its pesticide acceptable salt is used for preparing insecticide for controlling pests in agriculture or other fields.

[0034] The compounds of the present invention can be used to control and eliminate a wide range of health pests. In this specification, "insecticide" is a general term for all pests mentioned above. Examples of pests include, but are not limited to:

[0035] Blattaria: for example, German cockroach (Blattella germanica), American cockroach (Periplaneta american), house termite (Copotermes formosamus), etc.; Diptera: for example, housefly (Musca housefly), Aedes aegypti (Aedes aegypti), Delia platura (Delia platura), Culex fatigans (Culex fatigans), Anopheles sinensis, etc.

[0036] An insecticidal composition comprises the composition as an active component and an agriculturally acceptable carrier, wherein the active component accounts for 0.01-99.99% of the weight of the insecticidal composition.

[0037] The composition as defined above is prepared by mixing the compound of general formula (A) with a carrier. The active ingredient in such a composition may comprise a single compound of the invention or a mixture of several compounds.

[0038] The above composition can be applied in the form of a preparation. The compound of general formula (A) is dissolved or dispersed in a carrier as an active ingredient or formulated into a preparation so that it is easier to disperse when used as an insecticide; for example, these chemical preparations can be made into powders, wettable powders, emulsifiable concentrates, concentrated emulsions and microemulsions, suspoemulsions, granules, oils and ultra-low volume sprays, smoke-type, slow-release agents and other pesticide formulations. In these compositions, at least one liquid or solid carrier is added, and when necessary, a suitable surfactant can be added.

[0039] The carrier in the composition of the present invention is a substance that satisfies the following conditions: it is convenient for storage, transportation or handling after being formulated with the active ingredient. The carrier can be solid or liquid, including a substance that is usually gaseous but has been compressed into a liquid. Any carrier commonly used in the formulation of insecticidal compositions can be used.

[0040] The above composition can be used to kill or prevent sanitary pests.

[0041] It should be understood that various changes and modifications can be made within the scope of the present invention as defined by the claims.

[0042] In addition, the present invention also provides the use of the mandelonitrile alcohol ester compound or its pesticide acceptable salt as described in general formula (A) in preparing an insecticide, wherein the insecticide is used to kill pests, and the pests are houseflies (Musca dcmestica), Aedes aegypti, Delia platura, Culex fatigans, Anopheles sinensis, Blattella germanica, Periplaneta american, Copotermes formosamus, Solenopsis invicta, Tremex fuscicornis, etc. Compared with the prior art, the present invention has the following advantages and beneficial effects:

[0043] The compound of general formula (A) shows good biological activity against pests in agriculture, forestry and other fields; the compound of general formula (A) can be used as an insecticide, especially the compound of general formula (A) has a good toxic effect on sanitary pests such as housefly (Musca dcmestica), Aedes aegypti, Delia platura, Culex fatigans, Anopheles sinensis, Blattella germanica, Periplaneta american, Coptotermes formosamus, Solenopsis invicta, Tremex fuscicornis and the like. DETAILED DESCRIPTION

[0044] The present invention is further described in detail below in conjunction with the examples, but the embodiments of the present invention are not limited thereto. The raw materials involved in the present invention can be directly purchased from the market. For process parameters not particularly noted, conventional techniques can be used.

[0045] Synthesis Example 1: Preparation of Compound 1

[0046]

[0047] Add 100mL of 1,2-dichloroethane solvent to a 250mL four-necked flask with mechanical stirring, then add 12mmol of mandelonitrile, start stirring, and then add 15mmol of sodium bicarbonate. After cooling to 0°C, slowly add 10mmol of acryloyl chloride, and then react at room temperature for 1 hour. After the reaction is completed, add 20mL of water and continue stirring for 30 minutes, then stop stirring and let stand for 15 minutes, transfer to a 250mL separatory funnel, take the organic phase and remove the solvent by rotary evaporation at 25°C, and the obtained residue is dissolved in dichloromethane, separated and purified by column chromatography (the stationary phase is 300-400 mesh silica gel, and the mobile phase is petroleum ether: ethyl acetate = 60:40-50:50, v / v) to obtain a light yellow oily substance, which is identified as the target product of mandelonitrile alcohol esters after analysis.

[0048] Compound 1: light yellow oil, 1 H NMR (404MHz, Chloroform-d) δ7.99 (dq, J = 7.8, 1.7Hz, 2H), 7.62-7.54 (m, 1H), 7.49-7.40 (m, 3H), 7.40-7.25 (m, 3H), 6.71 (d, J = 0.7Hz, 1H). 13 C NMR(101MHz,Chloroform-d)δ165.11,133.26,132.93,130.46,130.06,129.48,1 29.47,129.40,129.39,129.20,128.85,128.84,128.16,128.09,116.79,66.49.

[0049] By taking the same steps as above and changing the corresponding raw materials, compound 1-80 can be synthesized, and the raw materials are all commercially available conventional pharmaceutical agents.

[0050] The compounds of the present invention show good activity against various pests in the agricultural field. The results of insecticidal activity determination are as follows:

[0051] Evaluation of the insecticidal activity of compounds against sanitary pests

[0052] Test insects: Culex pipiens, female adults that have not sucked blood on the 3rd to 5th day after emergence

[0053] Housefly, adult flies 3-4 days after emergence, half male and half female

[0054] German cockroach, 10-15 days old, half male and half female

[0055] Test method: Refer to GB / T 13917.2-2009 Indoor efficacy test and evaluation of public health insecticides for pesticide registration Part 2: Aerosol method.

[0056] Mosquitoes and flies: Use a cylindrical device.

[0057] The specific method is to put the test insects (30 houseflies or 30 mosquitoes) into the cylinder. After the test insects resume normal activities, the aerosol cylinder to be tested is horizontal, the nozzle is vertically downward, and aimed at the spray hole. The compound obtained in the above synthesis example is sprayed with acetone solution (the compound content in the spraying solution is 1.0±0.1g), and the round hole is immediately plugged with a rubber plug. After 1 minute, the pull plate is pulled out, and the timing is immediately started. The number of knocked-down test insects is recorded at regular intervals. After 20 minutes, the knocked-down test insects are moved to a clean insect cage, the feeding standard is restored, and they are fed with 5% sugar water cotton balls. The number of dead insects is checked for 24 hours, and the unknocked test insects are calculated as live insects. The test should be repeated three times or more. After each test, the test device should be cleaned, and the mortality rate (%) should be calculated according to the formula mortality rate (%) = number of dead insects / number of test insects × 100%.

[0058] Cockroaches: Use a cylinder device without pulling the board. Place 20 German cockroaches in a cylinder with a circle of vaseline on the upper part of the inner wall and sealed with a 12-mesh iron screen. After the test insects resume normal activities, place the aerosol cylinder horizontally, aim the nozzle downward vertically at the spray hole, spray the compound obtained in the above synthesis example with acetone solution (the compound content in the spray solution is 1.0±0.1g), immediately plug the round hole with a rubber plug, start timing, record the number of knocked-down test insects at regular intervals, and transfer all test insects to a clean container after 20 minutes, resume standard feeding, feed with mixed feed blocks and soaked cotton balls, and check the number of dead insects in 72 hours. The test should be repeated three times or more. At the end of each test, the test device should be cleaned, and the mortality rate (%) should be calculated according to the formula mortality rate (%) = number of dead insects / number of test insects × 100%.

[0059] The synthesized compounds 1-80 were tested according to the above experimental steps.

[0060] The compound test concentration was 50 mg / L.

[0061] Compounds with greater than 90% mosquito mortality are:

[0062] 2-29,31-45,47-55,57,60,64,66-80

[0063] The compounds that caused fly mortality greater than 90% were:

[0064] 2-23, 26-27, 30-38, 40, 44, 49, 53-70, 73-80

[0065] Compounds that caused greater than 90% mortality in cockroaches include:

[0066] 2-10,13,19,22-24,30,34,37,40-41,44-48,51,54,60-63,65,67-71,73-75,77-80

[0067] The above embodiments are preferred implementation modes of the present invention, but the implementation modes of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A mandelonitrile alcohol ester compound, characterized in that: The compound is a compound represented by formula (A) and a pharmaceutically acceptable salt thereof, In the formula, R1 can be selected from hydrogen, C 1-6 Alkyl, substituted or unsubstituted C 6-12 Aryl, substituted or unsubstituted C 5-12 Heteroaryl; wherein the substituted refers to being substituted by one or more substituents selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl; R2 is hydrogen, C 1-6 Alkyl, halogenated C 1-6 Alkyl or halogenated C 1-6 Alkoxy; R3 can be selected from substituted or unsubstituted C 6-12 Aryl; wherein the substituted refers to being substituted by one or more substituents selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl; R4 can be selected from hydrogen, C 1-6 alkyl; In the formula, the cross connecting R1, R2, and R4 represents a double bond.

2. The mandelonitrile alcohol ester compound according to claim 1, characterized in that: The compound is a compound represented by formula (A) and a pharmaceutically acceptable salt thereof, wherein: R1 is hydrogen, C 1-3 Alkyl, substituted or unsubstituted C 6-8 Aryl, substituted or unsubstituted C 5-8 Heteroaryl; wherein the substituted refers to being substituted by one or more substituents selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, carboxyl, amino, nitro, C 1-6 Alkyl, halogenated C 1-6 Alkyl, C 1-6 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl, halogenated C 3-6 Cycloalkyl; R2 is hydrogen, C 1-3 Alkyl, halogenated C 1-3 Alkyl, halogenated C 1-3 Alkoxy; R3 is substituted or unsubstituted C 6-8 Aryl; wherein the substituted refers to being substituted by one or more substituents selected from the group consisting of hydrogen, halogen, hydroxyl, cyano, carboxyl, nitro, C 1-3 Alkyl, halogenated C 1-3 Alkyl, C 1-3 Alkoxy, halogenated C 1-6 Alkoxy, C 3-6 Cycloalkyl; R4 can be selected from hydrogen, C 1-3 alkyl.

3. The mandelonitrile alcohol ester compound according to claim 2, characterized in that: The compound is the following compound and a pharmaceutically acceptable salt thereof, 4. A pesticide composition, characterized in that: The composition contains the compound represented by formula (A) as claimed in claim 1 and a pharmaceutically acceptable salt thereof.

5. The use according to claim 1 or 4, characterized in that: The use of the compound represented by formula (A) and its pharmaceutically acceptable salt according to claim 1 or the pesticide composition according to claim 4 in controlling and eliminating sanitary pests.

6. An insecticidal composition, characterized in that: The insecticidal composition comprises the composition of claim 4 as an active component and an agriculturally acceptable carrier, wherein the active component accounts for 0.01-99.99% by weight of the insecticidal composition.

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