KR820000580B1 - Process for preparing 1,4-benzoazine derivatives - Google Patents

Abstract

The process for preparing 1,4-benzoazine derivatives, useful for disinfectants, was described. 1,4-Benzoazine derivatives, formula (I), was prepared by reacting formula (VIII) with akylating agents. The formula (VIII) was prepared by reacting base, such as sodium hydroxide or potassium hydroxide, with akylating agents, alkyl halide or dialkyl sulfate, in the proper solvents, at 0-40oC for 0.5-10hr. It could be used independently and was used for various dosage form, powder, moisture powder, oil sprayer, aerosol, tablets, granules.

Description

Method for preparing 1,4-benzoazine derivative

The present invention relates to a process for the preparation of the novel 1,4-benzoazine derivatives of the following formula (I) useful as agricultural or horticultural fungicides.

Wherein R ₁ is a halogen atom or a methyl group, R ₂ is a lower alkyl group such as methyl or ethyl, and X and Y are each an oxygen or sulfur atom. As work conditions and working habits in the agricultural sector change, interest has focused on finding new chemicals that can combat a broader range of phytopathogenic microorganisms in a simpler way. In other words, an effective compound capable of simultaneously inhibiting two or more phytopathogenic microorganisms in terms of easy handling has been required, and in various applications, these compounds may be applied to leaves in the form of a dispersant, an emulsion, a wet powder, a fine granule, or a spray agent. There is a need for compounds that can be used in various ways, such as immersion and soil application in the form of emulsions, wet powders, suspended oils, granules and the like.

In addition, these compounds are less toxic to humans, livestock and fish and must be relatively easily broken down. With this in mind, our hard work has shown that the 1,4-benzoazine derivatives of Structural Formula (I) cause numerous plant pathogenic microorganisms, such as picomycetes (e.g., Mucospi Nessense, phytophthoracapcice, phytium apanidermatum), ascomycetes (e.g., Monironia fruitigena, neurosporacrasa, gibberella zeae, sclerotinia sclerotium, myco Sperella Melonis, Glomerella Singulata, Giberella Fujikuroi, Cocliobolus Miavianus, Venturia Inaculias Vassidiomycetes (e.g., Cortisium Rolfsee, Lisantonia Solani, Fuchsia Graminis), Letter Imperfections (e.g. Aspergillus niger, Hussaria oxysporum f, Cucumerinum, Cladosporium Cucumerinum, Pycurularia orizae, Cletotricum Lagenariaum, Helmintos Leeum Shigeru Rana deum, Bell tisil Solarium albo - ahteurum, Botrytis cine Leah, Puerto Winiah found that the ahroyi Dia), and shows antibacterial activity in other bacteria (eg, Xanthomonas duck characters).

The compound of the present invention is particularly effective for suppressing rice blast (pyrichloria oryzae) and stem rot (Helmintosporium sigmide) of rice, which are serious diseases of rice.

They can be spread out in any of the three application methods, either in front of them or in submerged or soil spreads, and have a better inhibitory effect. These compounds also have good vapor action, so you can adopt an application method that makes the most effective use of this particular property. In addition, the 1,4-benzoazine derivatives of formula (I) are very fast and difficult to obtain from methods of spreading on known leaves, spraying on the surface of water, or spreading on soil, which have been used to distribute agricultural and horticultural fungicides to rice blasts. Also has a strong lasting effect. They are also extremely toxic to warm-blooded animals (eg mice, rats, chicks) and fish (eg carps, freshwater fish) and rarely remain in crops.

These objects and advantages of the present invention will be apparent from the following description.

1,4-benzoazine derivatives of the structural formula (I) of the present invention are known from J, chem. By Ludon and Ogg. All are novel compounds except 2,3-dihydro-4,5-dimethyl-3-oxobenz-1,4-oxazine, described in Soc, 739-744 (1955). However, this publication does not mention the biological activity of these compounds. Therefore, we first discovered the various useful facts mentioned above and completed this invention.

The 1,4-benzoazine derivative of the structural formula (I) of the present invention can be made by various methods, but representative examples thereof are described below.

A 1,4-benzoazine derivative of formula (I), wherein Y is an oxygen atom, may be prepared by reacting a benzoazine derivative of formula (G) (G. Mann, J. C. S. 1945, 893-909) with an alkylating agent.

Wherein X and R are as described above.

In the above process, the benzoazine derivatives of formula (VIII) may be selected from suitable solvents such as water, ethanol, methanol, benzene, toluene, xylene, tetradrafurfuran, dioxane, ethyl ether, chloroform, carbon tetrachloride, DMF, DMSO or mixtures thereof. In the presence of bases such as sodium hydroxide, potassium hydroxide, sodium, sodium hydride, potassium t-butoxide, sodium ethoxide, sodium methoxide and the like (e.g. methyl iodide, bromomethyl, ethyl iodide, bromine Treatment with a suitable alkylating agent such as moethyl) or dialkylsulfate (e.g. dimethylsulfate, diethylsulfate) at a suitable temperature of 0-140 ° C for 0.5-10 hours. The crystal product is obtained, filtered and dried. Otherwise, the reaction mixture is poured into water, extracted with a suitable organic solvent, dried, and the solvent is removed to obtain the desired product. The product thus separated can be further purified according to a known method such as recrystallization or column chromatography.

Specific examples of the 1,4-benzoazine derivatives of formula (I) are shown in Table 1 below.

TABLE 1

Substantially realistically preferred methods for preparing the benzoazine derivatives of formula (I) are described in detail in the following examples.

EXAMPLE

=1.6173인 2,3-디하이드로-4-에틸-5-클로로-1,4-벤조티아진-3-은 2.1g을 얻었다.0.6 g of sodium hydroxide and 2.0 g of 2,3-dihydro-5-chloro-1,4-benzothiazine-3- were dissolved in 20 ml of methanol, and 1.9 g of dimethyl sulfate was added dropwise thereto while stirring at room temperature. The reaction mixture was stirred at 60 ° C. for 3 hours and poured into water. The mixture was extracted three times with 30 ml of chloroform, the extracts were combined, dried over magnesium sulfate, and the solvent was removed under reduced pressure.

2.1 g of 2,3-dihydro-4-ethyl-5-chloro-1,4-benzothiazine-3- with = 1.6173 was obtained.

Elemental Analysis as C ₁₀ H ₁₀ NSOCl

Calculation: C 52.74% H 4.44% N 6.15% Cl 15.57%

Found: 52.69 4.51 6.30 15.64

In actual use of the 1,4-benzoazine derivative of formula (I) as an agricultural and horticultural fungicide, the compound may be used alone without mixing with other ingredients such as carriers and diluents. However, for convenience of use, it is used as a commonly used formulation such as, for example, powder, wetting acid, oil spray, aerosol, tablets, emulsion concentrates, granules and microgranules.

In order to mold these preparations, the 1,4-benzoazine derivatives of formula (I) may be converted into mineral powders (e.g., talc, bentonite, montmorillonite, mud, kaolin, diatomaceous earth, mica, apatite, vermiculite, gypsum, calcium carbonate, Pyrophyllite, biotite, pumice, sulfur, activated carbon, slaked lime, plant powder (e.g., soybean, wheat, wood, walnut bark, sawdust, bark, bran, plant extract residue, tobacco, starch, crystalline cellulose), Polymer powders (e.g. petroleum resins, polyvinyl chloride, dharma gum, ketone resins), fiber products (e.g. paper, corrugated cardboard, old cloth), compound fertilizers (e.g. ammonium sulfate, ammonium phosphate, ammonium nitrate Solid carriers or diluents, such as um, urea, ammonium chloride), alumina or waxes, or alcohols (e.g. methanol, ethanol, ethylglycol, benzyl alcohol), aromatic hydrocarbons (e.g. benzene, toluene, xylene, methylnaphthalene), aliphatic Hydrocarbons (e.g. kerosene, Acids), chlorinated hydrocarbons (e.g. chloroform, carbon tetrachloride, monochlorobenzene), ethers (e.g. diethyl ether, dioxane, tetrahydrofuran, ethylene glycol, ethyl ether), ketones (e.g. acetone, methyl ethyl ketone, Cyclohexanone), esters (e.g. ethyl acetate, butyl acetate, ethylene glycol acetate), acid amides (e.g. N, N-dimethylformamide), nitriles (e.g. acetonitrile) or sulfoxides (e.g. dimethyl sulfoxide May be mixed with a liquid carrier or diluent. Binders and / or dispersants, if desired (e.g., gelatin casein, sodium alginate, CMC, starch, gum arabic powder, lignosulfonate, bentonite, polyoxypropylene glycol ether, polyvinyl alcohol, pine oil, liquid or solid paraffin) , Stabilizers (e.g. isopropylphosphate, tricresyl phosphate, tall oil, epoxy oils, surfactants, fatty acids, fatty acid esters), emulsifiers (e.g. alkylsulfonates, polyoxyethylene alkylsulfates, alkylarylsulfonates, polyethylene Other additives such as glycolalkyl ethers, polyoxyethylene alkylaryl ethers), wetting agents (eg dodecylbenzenesulfonate, lauryl sulfate) can be mixed into the formulation.

This formulation also contains, for example, N- (3,5-dichlorophenyl) -1,2-dimethylcyclopropyl-1,2-dicarboximide, Sn-butyl S'-P-tert-butylbenzyl N-3 -Pyridylthiocarbonamidate, 0,0-dimethyl 0-2,6-dichloro-4-methylphenylphosphothioate, methyl N-benzimidazol-2-yl-N- (butylcarbamoyl) carb Barmate, N-trichloromethylthio-4-cyclohexene-1,2-dicarboxymid, cis-N- (1,1,2,2, -tetrachloroethylthio) -4-cyclohexene-1, 2-dicarboximide, polyoxine, streptomycin, zinc ethylene-bis (dithiocarbamate), zinc dimethylthiocarbamate, manganese ethylene-bis (dithiocarbamate), bis (dimethylthiocarbamoyl ) Disulfide, tetrachloroisophthalonitrile, 8-hydroxyquinoline, dodecylguanidine acetate, 5,6-dihydro-2-methyl-1,4-oxathion-3-one-carboxanilide, N'- Dichlorofluorome Thio-N, N-dimethyl-N'-phenylsulfamide, 1- (4-chlorophenoxy) -3,3-dimethyl-1- (1,2,4-triazol-1-yl) -2- Commonly used swelling agents and / or other antifungal agents such as butanone, 1,2-bis (3-methoxycarbonyl-2-thio-ureido) benzene and the like.

Further, the 1,4-benzoazine derivatives of formula (I) may be, for example, 0,0-dimethyl-0-4-nitro-m-tolylphosphorothioate, 0-P-cyanophenyl 0,0-dimethyl Phosphorothioate, 0-P-cyanophenyl 0-ethylphenylphosphonothioate, 0,0-dimethyl SN methylcarbamoylmethyl phosphorodithioate, 2-methoxy-4H-1,3,2 -Benzodioxaphosphorin-2-sulfide, 0,0-dimethyl S-1-ethoxycarbonyl-1-phenylmethylphosphorodithioate α-cyano-3-phenoxybenzyl-2- (4- It can be used in combination with pesticides such as chlorophenyl) isovalerate, 3-phenoxybenzyl 2,2-dimethyl-3- (2,2-dichlorovinyl) cyclopropane carboxylate, 3-phenoxybenzyl chrysanthate, etc. have.

And in no case does the inhibition of each compound decrease. Therefore, it is possible to simultaneously suppress two or more harmful microorganisms and insects. They can also be used in combination with agricultural chemicals such as anti-neutral and tick pesticides and fertilizers.

Such formulations generally contain 0.1-95.0% by weight, preferably 0.2-90.0% by weight, of the active ingredient (including other mixed ingredients).

Appropriate amounts of this preparation are generally 10-1000 g per 10 ares, and the concentration is preferably 0.001-0.1% in the middle.

However, since the amount and concentration vary depending on the form of the preparation, the time of use, the method of use, the site of use, the disease and the crops, the amount and concentration may be increased or decreased as appropriate.

The actual type of fungicide composition according to the invention is described in detail in the following examples. Where parts and% are both expressed in weight.

Formulation Example 1 Powder

2 parts of compound (1) and 98 parts of clay are mixed to form a powder containing 2% of the active ingredient. When used, this powder is just spread.

Formulation Example 2 Powder

Completely mix 3 parts of Compound (2) and 97 parts of talc to make a powder containing 3% of the active ingredient.

Formulation Example 3: Wet Powder

50 parts of compound (5), 2.5 parts of dodecylbenzenesulfonate as a humectant, 2.5 parts of sodium lignosulfonate as a dispersant, and 45 parts of diatomaceous earth were mixed thoroughly to make a wet powder containing 50% of the active ingredient. The wet powder is diluted with water to spray the resulting solution.

Formulation Example 4 Emulsified Concentrate

10 parts of compound (6), 40 parts of dimethyl sulfoxide, 40 parts of xylene, and 10 parts of polyoxyethylene dodecylphenol ether as emulsifiers are mixed to obtain an emulsion concentrate containing 10% of the active ingredient. In use, this emulsion concentrate is diluted with water to spray emulsifiers.

Formulation Example 5 Granules

5 parts of compound (9), 93.5 parts of clay and 1.5 parts of polyvinyl alcohol as a binder are mixed, kneaded with water, granulated and dried to form granules containing 5% of the active ingredient. When used, the granules may be used as is or mixed with soil.

Formulation Example 6 Floating Granules

Ten parts of compound (10) are sprayed into 85 parts of pumice having an even particle size of 16-30 mesh so that the compound is wetted with pumice. Here, 5 parts of liquid paraffin is further sprayed to obtain floating granules containing 10% of the active ingredient. In use, this granule is used as it is.

Formulation Example 7 Epidermal Granules

10 parts of compound (13) are sprinkled onto 77 parts of silica sand having a particle size of 16-30 mesh, and then sprayed with 3 parts of 10% polyvinyl alcohol solution. This mixture is mixed with 10 parts of charcoal to make a gel granule containing 10% of the active ingredient. In use, this granule is used as it is.

Formulation Example 8 Granules

10 parts of compound (14), 30 parts of bentonite, 1 part of calcium lignosulfonate, 0.1 part of sodium lauryl sulfate, and 58.9 parts of clay are mixed.

The mixture is kneaded with water and passed through a sieve with a mesh size of 7 mm to make granules and then dried. In this way, granules containing 10% of the active ingredient are obtained. In use, use the granules as they are or as a solution diluted with water.

Formulation Example 9 Oil-Based Solution Diffused to Water Surface

1 part of compound (4), 10 parts of polyoxypropylene glycol monoether and 89 parts of kerosene are mixed to form an oil-based liquid dispersion which is diffused on the water surface containing 1% of the active ingredient. Use this liquid as is.

Several test results demonstrate the antimicrobial effect of the 1,4-benzoazine derivatives of formula (I) as shown in the test examples below. Here, parts are calculated by weight.

Test Example 1: Rice Blast Inhibitory Effect-Spray on Leaves (Prevention Effect)

In the rice (Kinki No 33, 4-5 leaf state) cultured in a 9cm diameter container, the test compound in the form of an emulsion concentrate prepared according to the method described in Formulation Example 4 was diluted with water and sprayed with a spray bottle for 15 ml each. Sprayed. One day after spraying, the plants were sprayed with a spore suspension in Pycuraria Orissa and the inoculated containers were kept at room temperature of 24-26 ° C. and at least 90% humidity. After leaving for 4 days, the extent of infection was measured in% of infected leaf surface area to test the inhibitory effect.

The results are shown in Table 2 below.

Disease suppression was calculated according to the following equation.

TABLE 1

TABLE 2

*… 0,0-diisopropyl-Sbenzylthiophosphate (48% emulsion concentrate)

**… Diisopropyl-1,3-dithiotan-2-ylidenemalonate (40% emulsion concentrate)

Test Example 2: Bleeding Inhibitory Effect-Scattering on Leaves (Residual Effect)

In a rice (kniki No 33, 4-5 leaf) cultured in a 9 cm diameter container, the test compound in the emulsion concentrate prepared in the same manner as in Preparation Example 4 was diluted with water and sprayed with a sprayer for 15 ml each. Sprayed. Four days after spraying, the spore suspension was sprayed onto the plants with Pycurularia Orissa and the inoculated containers were maintained at a constant room temperature of 24-26 ° C. and at least 90% humidity. After 4 days, the disease severity is measured by infected leaf area and the inhibitory effect of the test compound is examined. The results are shown in Table 3 below and the calculation of disease severity and percent inhibition was performed as in Test Example 1.

TABLE 3

*… 0,0-diisopropyl-S-benzylthiophosphate (48% emulsion concentrate)

**… 0-ethyl-S, S-diphenyldithiophosphate (30% emulsion concentrate)

Test Example 3 Rice Blast Inhibitory Effect-Underwater Spray

To the rice (kinki No 33, 5-6 leaf state) incubated with water in a Wagner container (1/500), the granular test compound prepared in the same manner as in Preparation Example 6 was sprayed in water. It was. The test granules were uniformly dispersed to 500 g of active ingredient per 10 arbors on the water surface and kept at a depth of 4-5 cm for a specified time before the container was inoculated with test microorganisms in a greenhouse.

Four and 30 days after the compound was sprayed, the spore suspension was sprayed onto the plants with Pycurularia Orissa and the inoculated vessels were kept constant at room temperature of 24-26 ° C. and at least 90% humidity. After 4 days the severity of the disease was tested by measuring the percentage of leaf area infected and the inhibitory effect was determined as in Test Example 1.

The results are shown in Table 4 below.

TABLE 4

*… 0,0-diisopropyl-S-benzylthiophosphate (17% granules)

**… Diisopropyl-1,3-dithioran-2-ylidenebaronate (12% granules)

Test Example 4: Rice fever suppression effect-soil spray test

An emulsified concentrate prepared in the same manner as in Formulation Example 4 in rice (kink; No 33, 5-6 leaf state) cultured in a Wagner container (/ 5000) was diluted with water to 500 g of active ingredient per 10 argans on the soil surface. Spray the appropriate amount. After 4 and 30 days, the plants were sprayed with Pycurularia Orissa spore suspension and the inoculated vessels were kept constant at temperatures above 24-26 ° C. and at least 90% humidity. After 4 days, the severity and inhibitory effects of the disease were measured in the same manner as in Test Example 1.

The results are shown in Table 5 below.

TABLE 5

*… 0,0-diisopropyl-S-benzylthiophosphate (48% emulsion concentrate)

**… Diisopropyl-1,3-dithiotan-2-ylidenemalonate (40% emulsion concentrate)

Test Example 5: Rice fever inhibitory effect: graft spray test

The granulated test compound prepared in the same manner as in Formulation Example 5 was sprayed onto the soil (Kinki No 33, 3 leaf state) cultured in a transplant plate of 30 × 60 × 3 cm. The test granules were evenly sprayed on the soil surface at a rate of 50 g of compound per nailing plate. After 24 hours, the treated plants were removed from the plate by 1 cm 2 of soil and transplanted into a Wagner container (1/5000). 45 days after transplantation, the plants were sprinkled with spore suspension on Pycurularia Orissa and the inoculated containers were kept at 24-26 ° C. room temperature and at least 90% humidity. After 4 days, the disease severity was measured by observing the leaf leaf area%, and the inhibitory effect was measured as in Test Example 1, and the results are shown in Table 6 below.

TABLE 6

*… 0,0-diisopropyl-S-benzylphosphorothiolate (17% granules)

**… Diisopropyl-1,3-dithioran-2-ylidenebaronate (12% granules)

Test Example 6: Leaf spot inhibition effect by parasite spores: leaf spray test

In a rice (kinki No 33, 4-5 leaf) cultured in a container (9 cm in diameter, 4 plants per container), the test compound in the emulsion concentrate prepared in the same manner as in Preparation Example 4 was diluted with water. 15 ml per container was sprayed with an atomizer. One day after spraying, a mycelial plate (5 mm in diameter) of Helmintosporium Sigmoideum cultured in PSA medium was attached to the shell of each stem and the inoculated container was kept at a temperature of 28 ° C. After 4 days, the severity of the disease is determined by measuring the length of the infected stem bark and calculated using the following equation.

Inhibitory effect was measured as in Test Example 1 and the results are shown in Table 7 below.

TABLE 7

*… 0-ethyl S, S-diphenyldithiophosphate (30% emulsion concentrate)

Claims (1)

A method for preparing a 1,4 benzoazine derivative of the following structural formula (I) by reacting a benzoazine derivative of the following structural formula (i) with an alkylating agent.

Wherein R ₁ is a halogen atom or a methyl group, R ₂ is a methyl or ethyl group and X is an oxygen or sulfur atom.