RU2528419C2 - 3,5-dinitro-2-(arylamino)-n-(4-nitroaryl)benzamides, having rodenticide activity - Google Patents

Abstract

FIELD: chemistry.

SUBSTANCE: invention relates to substances having rodenticide activity and can be used in agriculture and at home to control rodents. The compounds are 3,5-dinitro-2-(arylamino)-N-(4-nitroaryl)benzamides of general formula (I): where: R₁=H, methyl; R₂=H, halide, alkyl, alkoxy; R₃=H, halide, alkyl, alkoxy, acetyl, cyano; R₄=H, halide, alkyl, acetylamino, trifluoromethyl, except H with R₁, R₂, R₃, R₅, R₆, R₈ simultaneously denoting H; R₅=H, halide, methyl; R₆=H, halide, methyl; R₇=H, halide; R₈=H, halide.

EFFECT: 3,5-dinitro-2-(arylamino)-N-(4-nitroaryl)benzamides of general formula

(I), intended for producing the most effective rodent control agents.

4 tbl, 1 ex

Description

The invention relates to substances with rodenticidal activity, and can be used in agriculture and in everyday life to control rodents.

For the extermination of rodents, anticoagulants are currently used mainly, causing internal bleeding in rodents, which leads to their death.

By their chemical nature, anticoagulants are acetylindanedione. The best known from this group of chemical compounds are diphenacin, chlorfacinone, ethylphenacin, isopropylphenacin.

Anticoagulants are quite effective, however, these drugs must be used for a long time. Indoors they are used for at least 5-15 days, and in the field 1-2 months. Anticoagulants are characterized by a relatively rapid development of resistance. Anticoagulants have low efficiency when used to combat small rodents, especially in the field [1, 2].

Anticoagulants are characterized by a relatively rapid development of resistance. Overcoming resistance is possible when using new in structure chemical compounds that differ from acetylindanediodes.

The purpose of the invention is the creation of the most effective drugs for rodent control.

The problem is solved by the production and use of new chemical compounds for rodent control, which are 3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides of the general formula (I).

where: R ₁ = H, methyl;

R ₂ = H, halogen, alkyl, alkoxy;

R ₃ = H, halogen, alkyl, alkoxy, acetyl, cyano;

R ₄ = H, halogen, alkyl, acetylamino, trifluoromethyl with the exception of H with the simultaneous value of R ₁ , R ₂ , R ₃ , R ₅ , R ₆ R ₈ equal to H;

R ₅ = H, halogen, methyl;

R ₆ = H, halogen, methyl;

R ₇ = H, halogen;

R ₈ = H, halogen.

3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides (I) were synthesized using 2-chloro-3,5-dinitrobenzoic acid (II) as the starting compound according to the scheme below:

2-Chloro-3,5-dinitrobenzoic acid (II) is converted to the acid chloride (III), which acylates 4-nitroanilines (IV, R ₇ = R ₈ = H), 2-halide-4-nitroaniline (IV, R ₇ = halogen, R ₈ = H) or 2,5-dihalo-4-nitroaniline (IV, R ₇ = halogen, R ₈ = halogen). The result is 2-chloro-3,5-dinitro-N- (4-nitroaryl) benzamides (V).

Then, the obtained benzamides (V) are condensed in chlorine in the 2nd position with aniline, N-methylaniline or with substituted anilines (VI), forming 3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides (I) containing rings A, B and C. in their structure.

A total of 60 compounds were synthesized, which are 3,5-dinitro-2-arylamino-N- (4-nitroaryl) benzamides (I). The structure, as well as physico-chemical properties for these compounds are shown in table 1.

Table 1 shows the numbers of compounds, substituents from R ₁ to R ₈ , the melting point of the compounds. Chromatographic mobility of the compounds R _S relative to the compound N- (2-chloro-4-nitrophenyl) -3,5-dinitro-2- (phenylmino) benzamide was determined by thin-layer chromatography on silica gel (Merck plates). For thin layer chromatography, a 3: 1 hexane: ethyl acetate system was used.

The IR and PMR spectral data for each compound are also given.

All synthesized compounds were tested for rodenticidal activity (see table 2). The bait containing the test compound, in a concentration of from 0.001 to 0.80%, was fed to white mice. During the experiment, rodents were given the right to choose poisonous or non-poisoned food. The poisoned bait was given at the same time as food containing no drugs. After 1-2 days, the poison bait was removed. The death of animals was observed after 8-20 hours from the beginning of feeding, depending on the nature of the drug, its dose and concentration. Mortality of mice lasted for 1-5 days, mainly in the first two days.

3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides (I) showed rodenticidal activity in doses of 0.8 to 411 mg / kg of animal weight, depending on the structure of the test compound.

3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides (I) exhibit a rodenticidal effect in relation to other species of rodents: house mice, field voles and white rats. The efficacy data for some 3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides (I) are given in Table 3.

As can be seen from table 3, 3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides (I) can be used by any known method: with food, with water and in the form of briquettes.

The efficacy of 3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides (I) is higher than that of the known rodenticides, as shown by compound 39. The data are shown in table 4.

The proposed rodenticides are highly active, eat well with food, which is one of the positive properties of these compounds.

Examples

A. Determination of the rodenticidal activity of 3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamide (I).

In the experiments, white and domestic mice, field voles (M.arvalis), and white rats were used. When determining the toxicity of each dose of the drug, four to six animals were taken. Rodents were placed one in a separate cage. Poisoned bait and food without poison were simultaneously given in excess. After 1-2 days, the poisoned bait was removed. Observation of the animals was carried out for 5-7 days.

Animals were weighed at the beginning and at the end of the experiment. The amount of poison bait and feed consumed was determined every day throughout the experiment.

When working with white mice and white rats, we used a bait that meets European standards: 5% sugar, 0.2% salt, 20% flattened oats, 10% flour, 3% sunflower oil, the rest is a mixture of barley and wheat groats in a ratio of 1: 2. A mixture of barley and wheat grits was used as the feed of choice.

The composition of the bait when working with domestic mice and voles was as follows: 0.2% salt, 3% sugar, flour and sunflower oil, the rest was wheat grain. As the feed of choice used wheat. The test results are shown in tables 1-4.

B. Synthesis of 3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides (I).

The purity of the synthesized compounds was monitored by HPLC using a La Chrom instrument on a Nucleosil 100-5 C18 column. A methanol-water-phosphoric acid mixture is used as an eluent. Peaks are detected at a wavelength of 254 nm.

All synthesized compounds are characterized by melting points, R _S values in a thin layer relative to 3,5-dinitro-2-phenylamino-N- (2-chloro-4-nitrophenyl) benzamide, R _{S of} which is taken as 1.0. Thin layer chromatography was performed on Merck silica gel plates. Substances are detected as yellow spots or in UV light.

Compounds are also characterized by IR and PMR spectra. IR spectra in KBr pellets were recorded on an IFS-113v Bruker instrument; PMR spectra were recorded on DMSO-d6 on a Bruker DRX500 instrument.

Example 1. 2-Chloro-3,5-dinitro-N- (2-chloro-4-nitrophenyl) benzamide (V, R ₇ = Cl, R ₈ = H).

A mixture of 24.7 g (0.1 g mol) of 2-chloro-3,5-dinitrobenzoic acid, 13.1 g (0.11 g mol) of thionyl chloride and 0.1 g of dimethylacetamide in 80 ml of benzene is boiled for 3 hours . Benzene is distilled off, 10 ml of benzene is added to the residue and again distilled off. A solution of 17.3 g (0.1 g mol) of 2-chloro-4-nitroaniline in 70 ml of dioxane is added to the residue and boiled for 1 hour, after which the solvent is evaporated. The residue was triturated with methanol to give a solid precipitate, which was filtered off, washed with methanol and dried. 37.2 g of 2-chloro-3,5-dinitro-N- (2-chloro-4-nitrophenyl) benzamide are obtained in 93% yield. Melting point 204-205 ° C.

In a similar manner, 2-chloro-3,5-dinitro-N- (2,5-dichloro-4-nitrophenyl) benzamide is obtained. Melting point 230-232 ° C. Yield 85%.

Other 3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides (I) are similarly prepared.

Literature

1. Bykovsky V.A., Nikolaev N.N., Segal R.L. Agrochemistry, 1990, No. 6, pp. 104-123.

2. Babich N.B., Yakovlev A.A., Dragomirov K.A. Plant Protection and Quarantine, 2007, No. 2, pp. 44-46.

Rodenticidal activity of 3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides (I) for various species of rodents
Table 3 Type of rodent Connection number % poison in feed Death,% Lethal dose, mg / kg House mice 22 0.06 one hundred 24.3 52 0.05 one hundred 29.2 Common Vole 47 0,03 75 10.1 8 0.015 one hundred 1,0 White rats 8 0.02 one hundred 3.0 8 0.01 ^* fifty 1,2 8 0.04 ^** 75 2.7 * the drug was given with water ** the drug was given in briquettes

Toxicity to white mice of benzamide mixtures (compound 39) with known rodenticides
Table 4 Rodenticide % poison in feed Death,% Rats 0.50 0 Bromodialon 0.005 10 Fluoroacetamide 0.005 fifty Vacor 0.25 25 Benzamide 39 0.005 fifty

Claims (1)

Compounds of 3,5-dinitro-2- (arylamino) -N- (4-nitroaryl) benzamides of the general formula (I) exhibiting rodenticidal activity

where: R ₁ = H, methyl;
R ₂ = H, halogen, alkyl, alkoxy;
R ₃ = H, halogen, alkyl, alkoxy, acetyl, cyano;
R ₄ = H, halogen, alkyl, acetylamino, trifluoromethyl, with the exception of H, with a simultaneous value of R ₁ , R ₂ , R ₃ , R ₅ , R ₆ , R ₈ equal to H;
R ₅ = H, halogen, methyl;
R ₆ = H, halogen, methyl;
R ₇ = H, halogen;
R ₈ = H, halogen.