Oxazole ring-containing tetrahydropyridinopyrazole derivative, preparation method thereof and application of oxazole ring-containing tetrahydropyridinopyrazole derivative as herbicide

Abstract

The invention discloses an oxazole ring-containing tetrahydropyridinopyrazole derivative, a preparation method thereof and application of the oxazole ring-containing tetrahydropyridinopyrazole derivative as a herbicide. The oxazole ring-containing tetrahydropyridinopyrazole derivative has the following molecular structure expression and can be prepared by mixing pyraclonil and ethanolamine hydrochloride in a solvent and then adding a catalyst and an acid-binding agent for reaction; the oxazole ring-containing tetrahydropyridinopyrazole derivative has typical application as a paddy field herbicide. And # imgabs0 #.

Description

Technical Field

[0001] The present invention relates to an organic derivative, in particular to a tetrahydropyridopyrazole derivative containing an oxazole ring, a preparation method thereof and application thereof as a herbicide. Background Art

[0002] Pyraclonil, a tetrahydropyridopyrazole derivative, is a type of protoporphyrinogen oxidase (PPO) inhibitory rice field herbicide. Its mechanism of action is to target protoporphyrinogen oxidase (PPO) and inhibit chlorophyll synthesis in weeds.

[0003] As a PPO-inhibiting herbicide, bispyribac has the following characteristics:

[0004] (1) High selectivity, using chlorophyll in plant cells as the site of action, reducing toxicity to animals;

[0005] (2) The probability of weeds developing drug resistance is low. PPO inhibitors competitively inhibit the binding of PPO to plants, reducing the synthesis of chlorophyll in weeds themselves, making it difficult for weeds to develop drug resistance;

[0006] (3) Low dosage. PPO is a low-abundance protein. PPO inhibitors have a high affinity for the enzyme, and the ideal effect can be achieved at a relatively low dosage.

[0007] (4) It has no pollution to the environment, can be quickly decomposed in the soil, and has no impact on the groundwater system.

[0008] Bispyribac herbicide produces competitive inhibition by simulating substrate-enzyme binding to occupy active catalytic sites, achieving the effect of weed control. Due to the relative conservatism of the PPO active cavity, the possibility of weed resistance is greatly reduced. This excellent property has attracted much attention in the pesticide market. Since its launch, it has gained wide recognition and remarkable achievements in the Japanese rice field herbicide market. Therefore, it is of great significance to develop new tetrahydropyridopyrazole derivatives and explore their improved effects in biological activity. Summary of the invention

[0009] In order to solve the above technical problems, the present invention provides a tetrahydropyridopyrazole derivative containing an oxazole ring, a preparation method thereof and an application thereof as a herbicide. The tetrahydropyridopyrazole derivative containing an oxazole ring as a rice field herbicide exhibits a significant enhancement effect in terms of biological activity compared with bispyribac.

[0010] To achieve the above purpose, the technical solution adopted by the present invention is as follows:

[0011] First, a tetrahydropyridopyrazole derivative containing an oxazole ring has the following molecular structure expression:

[0012]

[0013] Secondly, a method for preparing a tetrahydropyridopyrazole derivative containing an oxazole ring as described above comprises the following steps:

[0014] After mixing bispyribac and ethanolamine hydrochloride in a solvent, a catalyst and an acid-binding agent are added to react; after the reaction is completed, extraction and purification are performed to obtain a product.

[0015] As a preferred embodiment of the preparation method of the present invention, the catalyst is selected from one or more of copper trifluoromethanesulfonate, zinc acetate, and trichloroisocyanuric acid; and / or,

[0016] The acid binding agent is one or more of potassium carbonate, sodium carbonate, sodium acetate, triethylamine, pyridine and piperidine.

[0017] As a preferred embodiment of the preparation method of the present invention, the amount of the catalyst added is 1-20% of the molar amount of bispyribac, such as 1%, 5%, 8%, 10%, 15%, 18%, 20%, etc.; and / or,

[0018] The amount of the acid binding agent used is 1.2-2 times the molar amount of bispyribac, such as 1.2 times, 1.4 times, 1.5 times, 1.8 times, 2.0 times, etc.

[0019] As a preferred embodiment of the preparation method of the present invention, the mixing amount of the bispyribac and ethanolamine hydrochloride is 1:(1-6) in a molar ratio, for example, 1:1, 1:2, 1:3, 1:4, 1:5, 1:6, etc.

[0020] As a preferred embodiment of the preparation method of the present invention, the reaction conditions are as follows: heating to 120-170°C for 10-30h, the reaction temperature is, for example, 125°C, 130°C, 135°C, 140°C, 145°C, 150°C, 155°C, 160°C, 165°C, etc., and the reaction time is, for example, 12h, 15h, 18h, 20h, 24h, 30h, etc.

[0021] As a preferred embodiment of the preparation method of the present invention, the solvent is one or more of tetrahydrofuran, ethanol, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile and water.

[0022] As a preferred embodiment of the preparation method of the present invention, after the reaction is completed, the reaction is filtered, the solution is evaporated to dryness or extracted without evaporation to dryness, the organic layer is collected, dried by spin drying, recrystallized, and purified to obtain the product.

[0023] The above preparation method is based on the consideration of saving production process, and the target product can be obtained by one-step reaction, which has the advantages of simple process and low production cost. However, this method should not be used as any limitation for obtaining the target product. Technicians in the field can select different preparation processes according to actual needs to obtain the same product, which generally does not affect the basic properties of the product.

[0024] Again, the present invention also provides a use of the tetrahydropyridopyrazole derivative containing an oxazole ring as described above or the tetrahydropyridopyrazole derivative containing an oxazole ring obtained by the method described above in a rice field herbicide.

[0025] The tetrahydropyridopyrazole derivatives containing an oxazole ring provided by the present invention have a broad-spectrum herbicidal activity, especially showing particularly significant herbicidal activity against barnyard grass, Leptochloa chinensis, Digitaria sanguinalis, Japanese alopecuroides and Lolium perenne, which provides a direction for the further development of new herbicides and lays a foundation for the preparation of compositions / preparations with the tetrahydropyridopyrazole derivatives containing an oxazole ring as the main herbicide active ingredient. DETAILED DESCRIPTION

[0026] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as limiting the present invention, but should be understood as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0027] It should be understood that the terms described in the present invention are only for describing special embodiments and are not intended to limit the present invention. In addition, for the numerical range in the present invention, it should be understood that each intermediate value between the upper and lower limits of the scope is also specifically disclosed. Each smaller range between the intermediate value in any stated value or stated range and any other stated value or intermediate value in the described range is also included in the present invention. The upper and lower limits of these smaller ranges can be independently included or excluded in the scope.

[0028] Unless otherwise indicated, all technical and scientific terms used herein have the same meanings as those generally understood by those skilled in the art. Although the present invention describes only preferred methods and materials, any methods and materials similar or equivalent to those described herein may also be used in the implementation or testing of the present invention. All documents mentioned in this specification are incorporated by reference to disclose and describe the methods and / or materials associated with the documents. In the event of a conflict with any incorporated document, the content of this specification shall prevail.

[0029] It will be apparent to those skilled in the art that various modifications and variations may be made to the specific embodiments of the present invention description without departing from the scope or spirit of the present invention. Other embodiments derived from the present invention description will be apparent to those skilled in the art. The present invention description and examples are exemplary only.

[0030] The words “include,” “including,” “have,” “contain,” etc. used in this document are open-ended terms, meaning including but not limited to.

[0031] The bispyribac herbicide used in the examples of the present invention was purchased from Hefei AiShang Agricultural Technology Co., Ltd.

[0032] The ethanolamine hydrochloride, zinc acetate, and triethylamine used in the examples of the present invention were purchased from Shanghai Bid Pharmaceutical Technology Co., Ltd.

[0033] Trichloroisocyanuric acid (TCCA) used in the examples of the present invention was purchased from Titan Technology Exploration Platform.

[0034] Unless otherwise specified, other raw materials and reagents can be purchased from commercial products.

[0035] In the following examples of the present invention, room temperature refers to 25±2°C.

[0036] [Example 1]

[0037] At room temperature, bispyribac and ethanolamine hydrochloride are mixed in a molar ratio of 1:6 and dissolved in acetonitrile. Trichloroisocyanuric acid with a molar amount of 3% of bispyribac as a catalyst and 200% of triethylamine as an acid-binding agent are added, and the temperature is raised to 120°C for reaction for 24 hours. After the reaction is completed, the mixture is filtered, the solvent is evaporated, and water and ethyl acetate are added for extraction. The organic layer is further evaporated and recrystallized to obtain the product, i.e., a tetrahydropyridopyrazole derivative containing an oxazole ring.

[0038] 1 H NMR (600 MHz, CDCl 3 )δ7.63(s,1H),4.54(t,J=9.5Hz,2H),4.31(t,J=9.5Hz,2H),4.04(t,J=6.1Hz,2H),3. 80(s,2H),3.29(s,1H),3.20(s,3H),2.70(t,J=6.5Hz,2H),2.07(s,2H),1.88(s,2H).

[0039] [Example 2]

[0040] At room temperature, bispyribac and ethanolamine hydrochloride are mixed in a molar ratio of 1:3.5 and dissolved in N,N-dimethylformamide. Zinc acetate with a molar amount of 15% of bispyribac as a catalyst and 150% of pyridine as an acid-binding agent are added, and the reaction is carried out at 170°C for 15 hours. After the reaction is completed, the mixture is filtered, the solvent is evaporated, and water and ethyl acetate are added for extraction. The organic layer is further evaporated and recrystallized to obtain the product.

[0041] [Example 3]

[0042] At room temperature, bispyribac and ethanolamine hydrochloride are mixed in a molar ratio of 1:2 and dissolved in ethanol. 12% of copper trifluoromethanesulfonate as a catalyst and 120% of sodium carbonate as an acid-binding agent are added to react at 140°C for 30 hours. After the reaction is completed, the mixture is filtered, the solvent is evaporated, and water and ethyl acetate are added for extraction. The organic layer is further evaporated and recrystallized to obtain the product.

[0043]

Application Test

[0044] The target product prepared in Example 1, a tetrahydropyridopyrazole derivative containing an oxazole ring and bispyribac were used as herbicides to conduct efficacy and toxicity tests. The specific methods are as follows:

[0045] Test weeds: Echinochloa crus-galli, Leptochloa chinensis, Digitaria sanguinalis, Japanese alopecuroides, and Lolium multiflorum.

[0046] Test crops: rice, wheat.

[0047] Sowing: Prepare several foam boxes (40×35×30cm) and mark them according to the types of crops / weeds. Each sample is equipped with 9 foam boxes and divided into 3 groups, with 3 in a group for parallel testing. Mark each group of samples as: experimental group, control group, and blank group. Plant the corresponding crops / weeds in the foam boxes according to the markings, and evenly sow 48 seeds in each box.

[0048] Preparation of the experimental group: Weigh 1 g of a tetrahydropyridopyrazole derivative containing an oxazole ring and dissolve it in 4 mL of dimethyl sulfoxide, add Tween and assist with ultrasonic oscillation, and the amount of Tween is configured to be 3% of the total volume to obtain the experimental group drug solution.

[0049] Preparation of the control group: Weigh 1 g of bispyribac and dissolve it in 4 mL of dimethyl sulfoxide, add Tween and assist with ultrasonic oscillation, and the amount of Tween is configured according to 3% of the total volume to obtain the control group drug solution.

[0050] Blank group preparation: Take 4 mL of dimethyl sulfoxide, add Tween and assist with ultrasonic oscillation, and the amount of Tween is configured according to 3% of the total volume to obtain the blank group drug solution.

[0051] The above solutions were diluted with water to the same multiple before use.

[0052] Spraying experiment: 7 days after sowing, the spraying amount was 210g.ai / hm 2 Each group of samples was sprayed with pesticides. 21 days after sowing, the efficacy and damage of each pesticide were observed and calculated.

[0053] Drug efficacy experiment

[0054] (1) According to the following formula, the inhibition rate of the number of weeds and the inhibition rate of fresh weight of the liquid medicine were calculated to characterize the herbicidal activity, and recorded in Table 1; wherein the treatment group refers to the experimental group or control group of the corresponding test;

[0055] Plant number inhibition rate (%) = (T 空白组 -T 处理组 ) / T 空白組 x 100%

[0056] T represents the number of plants of each weed seed that germinated (unit: plant);

[0057] Fresh weight inhibition rate (%) = (G 空白组 -G 处理组 ) / G 空白組 x 100%

[0058] G represents the fresh weight of each weed seed after germination (unit: g);

[0059] Table 1. Results of drug efficacy test

[0060]

[0061]

[0062] (2) According to the following formula, the inhibition rate of plant number and fresh weight of each crop by the liquid medicine was calculated to characterize the phytotoxicity activity, and recorded in Table 2; wherein the treatment group refers to the experimental group or control group of the corresponding test;

[0063] Plant number inhibition rate (%) = (L 空白组 -L 处理组 ) / L 空白組 x 100%

[0064] Among them, L represents the number of plants of each crop seed germination (unit: cm)

[0065] Fresh weight inhibition rate (%) = (M 空白组 -M 处理组 ) / M 空白組 x 100%

[0066] Where M represents the fresh weight of each crop seed after germination (unit: g)

[0067] Table 2. Results of pesticide damage test

[0068]

[0069] It can be seen from the above test results that the tetrahydropyrido-pyrazole derivatives containing oxazole rings provided by the present invention have significant herbicidal activity against the five selected weeds, not only maintaining the particularly outstanding herbicidal activity against Leptochloa chinensis, but also significantly higher plant number inhibition rates against barnyard grass, Digitaria, Japanese Alopecuroides, and Lolium multiflorum than those of oxadiazine, showing significantly enhanced herbicidal activity. In addition, the phytotoxicity test shows that the tetrahydropyrido-pyrazole derivatives containing oxazole rings provided by the present invention have little phytotoxicity against rice and wheat, with plant number inhibition rates of 4.14% and 3.64% respectively, which are less than 5.11% and 4.00% of oxadiazine. The above is only a preferred embodiment of the present invention, and it should be pointed out that for ordinary technicians in the field of technology, without departing from the method of the present invention, several improvements and supplements can be made, and these improvements and supplements should also be regarded as the protection scope of the present invention.

Claims

1. A tetrahydropyridopyrazole derivative containing an oxazole ring, characterized in that: It has the following molecular structure expression:

2. A method for preparing a tetrahydropyridopyrazole derivative containing an oxazole ring as claimed in claim 1, characterized in that: The following steps are involved: After mixing bispyribac and ethanolamine hydrochloride in a solvent, a catalyst and an acid-binding agent are added to react; after the reaction is completed, extraction and purification are performed to obtain a product.

3. The method for preparing a tetrahydropyridopyrazole derivative containing an oxazole ring according to claim 2, characterized in that: The catalyst is selected from one or more of copper trifluoromethanesulfonate, zinc acetate, and trichloroisocyanuric acid; and / or, The acid binding agent is one or more of potassium carbonate, sodium carbonate, sodium acetate, triethylamine, pyridine and piperidine.

4. The method for preparing a tetrahydropyridopyrazole derivative containing an oxazole ring according to claim 2 or 3, characterized in that: The amount of the catalyst added is 1-20% of the molar amount of bispyribac; and / or, The amount of the acid binding agent used is 1.2-2 times the molar amount of bispyribac.

5. The method for preparing a tetrahydropyridopyrazole derivative containing an oxazole ring according to any one of claims 1 to 4, characterized in that: The mixed amount of the bispyribac and ethanolamine hydrochloride is 1:(1-6) in terms of molar ratio.

6. The method for preparing a tetrahydropyridopyrazole derivative containing an oxazole ring according to any one of claims 1 to 5, characterized in that: The reaction conditions are: heating to 120-170°C and reacting for 10-30 hours.

7. The method for preparing a tetrahydropyridopyrazole derivative containing an oxazole ring according to any one of claims 1 to 6, characterized in that: The solvent is one or more of tetrahydrofuran, ethanol, N,N-dimethylformamide, N,N-dimethylacetamide, acetonitrile and water.

8. The method for preparing a tetrahydropyridopyrazole derivative containing an oxazole ring according to any one of claims 1 to 7, characterized in that: After the reaction is completed, the reaction is filtered, the solution is evaporated to dryness or extracted without evaporation to dryness, the organic layer is collected, spin-dried, recrystallized, and purified to obtain the product.

9. Use of the tetrahydropyridopyrazole derivative containing an oxazole ring as claimed in claim 1 or the tetrahydropyridopyrazole derivative containing an oxazole ring obtained by the method according to any one of claims 2 to 8 in a rice field herbicide.

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