CN116813522A - Preparation method and application of indole-containing benzenesulfonyl urea compound - Google Patents

Abstract

The invention discloses an indole-containing benzenesulfonyl urea compound and application thereof in pesticides, and belongs to the technical field of pesticides. The technical problem solved by the invention is to provide a novel compound which can be used as herbicide, bactericide and crop nutrition agent. The structural formula of the compound is shown in a formula I. The compound has novel structure, simple synthesis and better effectThe weeding performance has better inhibition activity on plant pathogenic fungi, has better promotion effect on the growth of crops, and lays a better foundation for the research and development of new pesticides.

Description

Preparation method and application of an indole-containing benzenesulfonylurea compound

Technical field

The invention relates to a method for synthesizing a novel indole-containing benzenesulfonylurea compound and its application in weeding, sterilizing, and promoting plant growth.

Background technique

Sulfonylurea compounds have been used in agriculture as herbicides since the 1970s. Their target is the ALS enzyme, which achieves herbicidal effects by inhibiting the synthesis of key amino acids in weeds. Because sulfonylurea herbicides have the advantages of high activity, easy degradation, and low dosage, they have always been a research hotspot at home and abroad. However, with the long-term and widespread use of herbicides, weed resistance has gradually increased. At the same time, in response to the national call for “reduce dosage and increase efficiency”, it is necessary to develop new herbicide varieties with multiple functions.

At present, common benzene sulfonylurea compounds are usually composed of three parts, namely, benzene ring, sulfonylurea bond, and heterocyclic ring. That is, the benzene ring and the heterocyclic ring are connected through sulfonylurea bond, and the sulfonylurea bond is through The nitrogen atoms outside the heterocyclic ring form bonds, and there are no reports on compounds that form sulfonylurea bonds through the nitrogen atoms inside the heterocyclic ring. In order for the nitrogen atoms in the heterocyclic ring to form a sulfonylurea bond, there must be at least one hydrogen on the nitrogen. Considering that indole has good biological safety, its derivatives usually have both phytonutrient and antibacterial effects, and the nitrogen atoms in its heterocyclic ring have the conditions to form a sulfonylurea bond, so indole-containing phenylsulfonyl The development of urea compounds is very meaningful for reducing dosage and increasing efficiency and coping with the growing resistance of weeds.

Contents of the invention

In order to solve the resistance problem of traditional sulfonylurea herbicides, the present invention breaks the convention and uses the nitrogen atoms in the heterocyclic ring to construct the sulfonylurea bond, and at the same time improves its antibacterial and antibacterial properties by selecting appropriate heterocyclic rings and substituents. Promote growth performance, thereby providing the preparation and application of a sulfonylurea compound containing an indole ring.

In order to achieve the above object, the technical solution adopted by the present invention is: a compound represented by formula I,

Formula I,

Among them, R ₁ is one of H, CN, F, OCH ₃ , CONH ₂ , CF ₃ or CHF ₂ , and the substitution position on the benzene ring is not limited; R ₂ is CH ₃ , F or SO ₂ CH ₃ A kind of, the substitution position on the benzene ring is not limited.

The present invention also provides a method for preparing indole-containing benzene sulfonylurea compounds. The chemical reaction equation and synthesis method are as shown in Formula III:

Formula III,

Mix an appropriate amount of R1 _- substituted indole compound with 1 times the equivalent of N,N-carbonyldiimidazole in a suitable solvent, add a small amount of catalyst and reflux for a certain period of time. After monitoring that the raw materials disappear, add 1 times the amount of N, N-carbonyldiimidazole to the reaction solution. Equivalent of R ₂ substituted benzene sulfonamide, continue the reflux reaction until the R ₂ substituted benzene sulfonamide disappears, the resulting mixture is concentrated under reduced pressure, the residue is fully stirred in an appropriate amount of dichloromethane, and the insoluble matter is obtained by suction filtration under reduced pressure. Filter the cake and dry it under vacuum to obtain the compound of formula I.

The indole-containing benzenesulfonylurea compounds of the present invention can be used to prepare herbicides, fungicides, and crop nutrients.

Compared with the existing technology, the present invention not only has better weeding ability, but also has better antibacterial effect. After degradation, it can still provide nutrients necessary for the growth of crops and promote the growth of crops. It is a A new type of herbicide with multiple functions.

Implementation

The present invention will be further described below with reference to examples. The purpose is to better understand the content of the present invention and reflect the substantive features of the present invention. Therefore, the examples cited should not be regarded as limiting the scope of protection of the present invention.

Example 1: Synthesis of Compound 1, the synthesis route is shown in Formula IV:

Formula IV,

Synthesis method: Add N,N' -carbonyldiimidazole (1.62 g, 10 mmol) and pyridine (79 mg, 1 mmol) to the acetonitrile solution of indole (1.17 g, 10 mmol) in sequence, and reflux the reaction under nitrogen protection. After 15 hours, add p-toluenesulfonamide (1.71 g, 10 mmol), and continue the reflux reaction under nitrogen protection for 8 hours. After the obtained mixture cooled to room temperature, it was concentrated under reduced pressure. The residue was fully stirred in dichloromethane and filtered. The filter cake was dried under vacuum to obtain N -p-toluenesulfonyl- 1H -indole-1-carboxamide (compound 1 ), as a white solid (2.5 g, 79.6%). LCMS[M+1]=315.1.

Example 2: Synthesis of Compound 2, the synthesis route is shown in Formula V:

Formula V,

To a solution of 5-trifluoromethyl- 1H -indole (1.85 g, 10 mmol) in dioxane , N,N' -carbonyldiimidazole (1.8 g, 11 mmol) and 4-dimethylamine were added successively Pyridine (122 mg, 1 mmol) was refluxed under nitrogen protection for 19 hours, p-fluorobenzenesulfonamide (1.75 g, 10 mmol) was added, and the reaction was continued under nitrogen protection for 10 hours. After the obtained mixture cooled to room temperature, it was concentrated under reduced pressure. The residue was fully stirred in dichloromethane and filtered. The filter cake was dried under vacuum to obtain N -((4-fluorobenzenesulfonyl)-5-(trifluoromethyl) -1H -indole-1-carboxamide (compound 2), as a light yellow solid (3.5 g, 90.6%). LCMS [M+1]=387.3.

Example 3:

The plate method was used to test the inhibitory rate of some indole-containing benzenesulfonylurea compounds on rapeseed seeds, and compared with the commercial nicosulfuron-methyl. The results are shown in Table 1:

Table 1 Inhibition rates of some compounds and nicosulfuron in rapeseed

From Table 1, both Compound 1 and Compound 2 showed higher inhibition rates, which means that this type of compound may have better herbicidal activity than nicosulfuron.

Example 4:

The in vitro antibacterial activity of some indole-containing phenylsulfonylurea compounds was determined using the punching method and compared with commercial nicosulfuron and norfloxacin. Select one strain each from Gram-negative bacteria, Gram-positive bacteria, and fungi for experiments. The experimental results are shown in Table 2:

Table 2 MIC (μg/mL) values of some compounds with nicosulfuron and norfloxacin

It can be seen from the results in Table 2 that compared to the specialized bactericides such as norfloxacin, the bactericidal abilities of Compound 1 and Compound 2 are relatively low and require a higher concentration to have an inhibitory effect. However, compared with In comparison with the herbicide Nicosulfuron-methyl, both Compound 1 and Compound 2 showed better bactericidal performance.

Example 5:

The performance of different compounds as a plant nutrient was investigated by testing their effects on promoting the germination of lettuce seeds with nicosulfuron.

Experimental plan: 1) Select plump lettuce seeds and wash them with clean water; 2) Prepare the compounds to be tested into solutions of 50, 100, 200, 500 and 1000 μg/mL with a 95:5 mixed solution of water and methanol; 3 ) Spread two layers of filter paper under each petri dish, and drop 2 mL of the above five concentration gradient solutions evenly; 4) Place in a light incubator, cultivate under 25-degree full-day light conditions, and count the number of seed germination every 12 hours. . The statistics are shown in Table 3:

Table 3 Effects of some compounds and nicosulfuron on lettuce seed germination number

As can be seen from the results in Table 3, the germination rate of lettuce seeds treated with solutions of Compound 1 and Compound 2 is higher than that of the traditional herbicide nicosulfuron, indicating that Compound 1 and Compound 2 have the effect of promoting germination.

Although the present invention has been described in detail through preferred embodiments, the present invention is not limited thereto. Those skilled in the art can implement the present invention according to their own understanding without departing from the spirit and essence of the present invention. Various modifications are made to the example, but these modifications all fall within the protection scope of the present invention.

Claims (6)

1. The compound whose structural formula is formula Ⅰ: Formula I, Among them, R ₁ is H, CH ₃ , CN, F, OCH ₃ , CONH ₂ , CF ₃ or CHF ₂ , and R ₂ is CH ₃ , F or SO ₂ CH ₃ . 2. The preparation method of the compound according to claim 1, characterized in that the synthetic method of the compound includes the following steps: 1) The R _1- substituted indole reacts with N,N' -carbonyldiimidazole in an organic solvent in the presence of a suitable catalyst to form an active intermediate, whose structure is shown in Formula II: Formula II; 2) Add R2 _- substituted benzene sulfonamide to the reaction solution obtained in step 1), continue the reflux reaction for a certain period of time, evaporate the solvent under reduced pressure, pour the residue into dichloromethane, filter the precipitate, and pass the precipitate through vacuum The indole-containing benzene sulfonylurea compound represented by formula I can be obtained by drying. 3. The compound synthesis step according to claim 2, characterized in that the catalyst in step 1) is one of 4-dimethylaminopyridine, 2,6-dimethylpyridine and pyridine, preferably 4-dimethylaminopyridine. Dimethylaminopyridine; the organic solvent is one of acetonitrile and dioxane, preferably acetonitrile. 4. Application of the compound as claimed in claim 1 and its dosage form of one or more pharmaceutically acceptable excipients in fungicides. 5. Application of the compound as claimed in claim 1 and its dosage form of one or more pharmaceutically acceptable excipients in crop nutrients. 6. Application of the compound as claimed in claim 1 and its formulation of one or more pharmaceutically acceptable excipients in herbicides.