JPH01221372A - Cyclic acylhydroxylamine derivative - Google Patents

Abstract

NEW MATERIAL:A compound shown by formula I [R is cycloalkyl, cycloalkylalkyl, aryl or arylalkyl (aryl means benzene nucleus, thiophene nucleus, pyridine nucleus or furane nucleus); A is -CO-, -SO2- or OC(=O)-; B is 3-6C alkylene which may be replaced with lower alkyl]. EXAMPLE:2-Cyclohexylsulfonyltetrahydro-1,2-oxazine. USE:An agricultural chemical, an intermediate for preformed chemical mediator, stabilizer, etc. Showing highly controlling effects on blast of rice plant, brown rust of wheat, etc. PREPARATION:An acylhydroxylamine derivative shown by formula II is reacted with a dihalide derivative shown by formula III (X and Y are halogen) in a solvent such as DMF, etc. in the presence of an acid binder (e.g. NaOH) at room temperature - the boiling point of the solvent to give a compound shown by formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION (Industrial Application Field) The present invention relates to a novel N-acyl cyclic hydroxylamine derivative represented by (I) below.

These compounds can be used as agricultural chemicals because they have a high control effect on rice blast and wheat rot, which are important diseases in rice and wheat cultivation, as shown in the reference test examples below. Furthermore, because it has a unique chemical structure, it can also be used as a chemical product, such as a synthetic intermediate for physiologically active substances such as agricultural chemicals and medicines, a stabilizer, a functional substance, or a synthetic intermediate thereof. Therefore, it is useful in the chemical industry including a drug manufacturing industry.

(Prior Art) Until now, as compounds having a cyclic acylhydroxylamine structure, ethoxycarbonyl isoxazolidine and 2-ethoxycarbonyltetrahydro-1,2-oxazine are listed in Journal of Chemical Society, 1942, p. 432. It is stated that it was obtained by the reaction of hydroxylamine with the corresponding dibromide. Furthermore, after hydrolyzing these compounds, 3,5-dinitrobenzoyl isoxazolidine and 2-(3,5-dinitro)benzoyltetrahydro-1,2-oxazine were obtained by reaction with 3,5-dinitrobenzoyl chloride. Says.

Furthermore, in Journal of Organic Chemistry Vol. 36, No. 2, p. 284 (1971), benzoyl isoxazolidine and 2-benzoyltetrahydro-1,2-oxazine are produced by the reaction of penzhydroxamic acid and dibromide. It is said that it was obtained. In addition, in Journal Op Heterocyclic Chemistry Vol. 6, No. 1, Page 111 (1969), 2-ethoxycarbonylhexahydro-1, After 2-oxazepine was obtained and hydrolyzed, it was converted into 2-acetylhexahydro-1°2-oxazepine.

On the other hand, an example of application to physiologically active substances is U.S. Patent No. 4.44.
No. 7,259 discloses that oxyphenoxypropionyl isoxazolidine derivatives are used as herbicides, and Dutch Patent Nos. 6,716 and 744 disclose that urea conductors having isoxazolidine and tetrahydro-1°2-oxazine are used as herbicides. As a herbicide, it is also used in the USSR Patent No. 5.
88,172 states that 2-n-hexanoyltetrahydro-1,3-oxazine has activity as a herbicide.

As for medicines, there are US Pat. Science Vol. 28 No. 10 No. 818 (197
3) and Journal of Pharmaceutical Sciences, Vol. 62, No. 8, p. 1392 (197
3 years), special benzoyloxazolidine, benzenesulfonylisoxazolidine, 2-benzoyltetrahydro-1°2-oxazine, and 2-benzoyltetrahydro-1,2-oxazepine, all of which have two or more methoxy groups on the benzene ring. It is said that it acts on the central nervous system and is effective as a tranquilizer.

However, there are no reports on the activity of these compounds as agricultural and horticultural fungicides.

(Problem to be solved by the invention) Rice and wheat cultivation are important agricultural fields that are responsible for the world's staple food.Therefore, in developed countries, cultivation is systematic and adequate pest control is carried out.

On the other hand, due to the need to exert a sufficient control effect against rice blast and wheat rot, which are important diseases of rice and wheat, the same chemical or a chemical with similar action has been sprayed multiple times. Therefore, there is always a fear that resistant bacteria or bacteria with low susceptibility will emerge when sprayed with drugs, and this problem has occurred with many drugs to date. In order to solve this problem, it is always a major challenge to develop new drugs with different skeletons from conventional drugs. On the other hand, known compounds similar to the compounds of the present invention have not been used as agricultural and horticultural fungicides, but according to the findings of the present inventors, they exhibit some plant disease control activity, but have no practical control effect. It is far from showing that. Therefore, the present invention seeks to solve this problem by providing novel compounds to replace these similar compounds.

(Means for Solving the Problems) In order to achieve the above object, the present inventors synthesized compounds having a large number of novel skeletons and conducted extensive studies on their usefulness. As a result, we succeeded in synthesizing a cyclic acylhydroxylamine derivative represented by the following general formula (1). We have also discovered that these conductors are new compounds that have not been described in literature, and that they have high control activity against rice blast and wheat rot, which are important diseases of rice and wheat.

Therefore, the gist of the present invention is the following general formula (I) [wherein R is a cycloalkyl group, a cycloalkylalkyl group, an aryl group or an arylalkyl group (however,
Aryl means a benzene nucleus, a pyridine nucleus, a thiophene nucleus or a furan nucleus, which nuclei may be substituted with up to two identical or different halogen atoms, lower alkyl groups or lower haloalkyl groups) and B represents an alkylene group with a carbon chain of 3 to 6 which may be substituted with a lower alkyl group, but when R is an unsubstituted benzene ring, A is a -C- group. is in the cyclic acylhydroxylamine conductor shown in [Summer].

Next, typical specific examples of the compound of the present invention represented by the formula (1) are shown in Table 1.

Table 1 The compounds listed in Table 1 are also referred to in the Examples and Test Examples below.

The compound of general formula (R) according to the present invention can be produced by the method described below. That is, the compound of formula (1) can be produced by a method comprising reacting an acylhydroxylamine derivative of formula (!■) below with a civalide derivative of formula (III) below.

(II) (Iris II)
(I) (In the formula, R, A, and B have the same meanings as above, and X and Y represent halogen atoms, which may be the same or different.) This reaction is usually carried out in a solvent using an acid binder. In the presence, a compound of formula (II) and a compound of formula (III
) can be achieved by mixing with the compound. Examples of solvents include hydrocarbons such as benzene, toluene, and xylene, ethers such as tetrahydrofuran and dioxane, nitrites such as acetonitrile and propionitrile, alcohols such as ethanol and engineered ethylene glycol, dimethylformamide, dimethylacetamide, etc. amides and dimethyl sulfoxide can be used. As the acid binder, inorganic bases such as sodium hydroxide, sodium hydride, and potassium carbonate, and organic bases such as sodium methoxide, sodium ethoxide, triethylamine, and pyridine can be used.

Although the reaction proceeds at room temperature, the reaction time can be shortened by heating up to the boiling point of the solvent. After the reaction is complete,
If salts of the acid binder are present, the target compound can be obtained by filtering them off and distilling off the solvent. Also, water and benzene, toluene, tetrahydrofuran,
Add an organic solvent such as chloroform to extract the target substance,
The target compound can also be obtained by distilling off the solvent. Examples of producing compounds of formula (I) are shown in Examples 1 to 5.

In addition, the compounds of the formula (II) and the formula (II+>>, which are the raw materials, are well-known compounds, and both can be produced by known methods.

The compound of general formula (I) produced as described above has activity for controlling rice blast and wheat rot in the agricultural and horticultural fields.

The method for formulating and using the compound of formula (1) as a disinfectant is as follows. That is, - the compound of formula (I) is mixed with suitable carriers and auxiliary agents, such as surfactants, binders, stabilizers, etc., and prepared by conventional methods into wettable powders, emulsions, solutions, and sol preparations (flowables). It may be formulated as a powder, an oil solution, a powder, a DL (driftless type) powder, a fine granule, a coarse powder, or the like.

The content of the compound of formula (I) in these preparations is as follows:
For emulsions, liquids, sols, and oils, 1 to 90% (by weight)
; the same applies hereinafter); in the case of powders, DL coarse powders, fine granules, and coarse powders, the range is 0.5 to 5%; in the case of granules, it is 1 to 10%.
It can be contained within a range of %. Formulation examples are shown in Reference Formulation Examples.

The method of using the compound of formula CI) as a fungicide is generally as follows. In other words, in the case of wettable powders, liquids, emulsions, sols (flowables), and oils, 500
When diluted ~2000 times, the active ingredient is generally 1-100
The solution is prepared at a concentration of 0.00 ppm. Then, per 10 ares, add 50~3001 of this diluted solution, usually 100~
200 JZ is sprayed on the foliage of the plant where the disease occurs.

In addition, liquids, emulsions, and sol (flowables) can be used as concentrated liquids without diluting them with water, or by diluting them up to 10 times with water. UL
V spraying agent), 50 to 3000 m per 10 are
An amount of approximately j2 is sprayed using a helicopter or the like.

In addition, for powders, DL coarse powders, fine powders, and coarse powders, apply 2 to 5 g (approximately 50 to 500 g of active ingredient) per 10 are to the leaves, soil surface, soil, or water surface of the diseased area of the plant. Sa-ru.

Example 1 Cyclohexylsulfonylhydroxylamine 17.9
A mixture of 21.8 g of 1,4-dibromobutane, 30.4 g of anhydrous potassium carbonate, and 200 al of acetonitrile was refluxed for 3 hours with stirring. After cooling, the salts were filtered off and the filtrate was concentrated. Add chloroform and water to the residue,
The organic layer was separated, washed with a 1N-NaOH solution and then with water, and dried over anhydrous sodium sulfate.

The solvent was distilled off under reduced pressure to obtain 21.4 g of the title compound as a pale yellow oil. When purified by silica gel column chromatography, it becomes a colorless oil with a concentration of 31.4
It showed 199.

15.3 g of phenoxycarbonylhydroxylamine,
23.0 g of 1,5-dibromopentane, 30.4 g of anhydrous potassium carbonate and 200 mJ of methanol! The mixture was refluxed for 6 hours with stirring. After cooling, the salts were filtered off and the filtrate was concentrated. Toluene and water were added to the residue, the organic layer was separated and washed with 1N-Na0II solution and then with water,
It was dried with anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 19.4 g of the title compound as a pale brown oil. Purification by silica gel column chromatography gave a colorless oil with n'' of 1.4854.

Example 3 Balatoluenesulfonylhydroxylamine 18.7g
A mixture of 15.6 g of 1-bromo-3-chloropropane, 11.5 g of potassium hydroxide, and 200 mfL of ethanol was stirred at 50° C. for 3 hours. After cooling, tetrahydrofuran, toluene and water were added and the organic layer was separated, washed with water and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure to obtain 19.1 g of the title compound as pale brown crystals. Recrystallization from a mixed solvent of hexane and ethyl acetate gave white crystals with a melting point of 93-94.5°C.

衷IL Tsuji A Paratrifluoromethylbenzoyl isoxaparatrifluoromethylbenzoylhydroxylamine 20.5
g11.3-Dibromopropane 20.281 Using 30.4 g of anhydrous potassium carbonate and 200 nl of acetonitrile, the reaction, treatment and purification were carried out in the same manner as in Example 1 to obtain 22.8 g of the title compound as a pale yellow oil.

When left at room temperature for a while, it crystallized, and when recrystallized from hexane, it became white crystals with a melting point of 54-55°C.

2-pyridylcarbonylhydroxylamine 13.8g
The reaction and treatment were carried out in the same manner as in Example 3 using 11.3 g of 1,3-dichloropropane, 8.2 g of sodium hydroxide and 200 mJ:l of ethanol to obtain 15.3 g of the title compound as a pale brown oil. Ta. When purified by silica gel column chromatography, it became a colorless oil with a nol of 4931.

Reference formulation example 1) (Powder) 2 parts of compound No. 2, PAP (physical property improver)
1 part and 97 parts of clay are uniformly mixed and ground to obtain a powder containing 2% of the active ingredient.

A total of 30 parts of the 2 compounds, 3 parts of calcium alkylbenzenesulfonate, 5 parts of polyoxyethylene nonylphenyl ether and 62 parts of clay were mixed uniformly and ground to contain 30% of the active ingredient. Obtain a hydrating powder.

By mixing and dissolving 30 parts of the compound of U-New Technology Compound O, 40 parts of methyl ethyl ketone and 30 parts of polyoxyethylene nonylphenyl ether, an emulsion containing 30% of the active ingredient is obtained.

4) l 11- 5 parts of compound No. 42, 1.5 parts of lauryl sulfate, 1.5 parts of calcium lignin sulfonate, 25 parts of bentonite and 67 parts of white carbon were mixed uniformly, and 15 parts of water was added thereto. The mixture is kneaded in a mixer and granulated, and dried in a fluidized fluid dryer to obtain granules containing 5% of the active ingredient.

Dish U1 - 10 parts of Gokami Compound No. 21 and 90 parts of ethyl cellosolve are mixed and dissolved to obtain an oil solution containing 10% of the active ingredient.

Compound No. 2 Compound 4 of Compound No. 2 B crushed to 10μ or less
0 parts of lauryl sulfate, 2 parts of sodium alkylnaphthalene sulfonate, 1 part of hydroxypropyl cellulose, and 55 parts of water were uniformly mixed to make an active ingredient of 40%.
Obtain a sol containing:

(Effects of the Invention) According to the present invention, a novel and useful compound having a unique chemical structure can be provided. These substances can be used as physiologically active substances, useful chemical products, or intermediates for their synthesis, but these compounds are especially useful in agriculture because they exhibit high control activity against rice blast and wheat rot in the agricultural and horticultural fields. It is promising as a horticultural fungicide. Moreover, as shown in the reference test examples, the bactericidal effect is superior to that of the compounds similar to the compounds of the present invention known so far, and is therefore useful.

A predetermined concentration chemical solution of a hydrating powder prepared according to Reference Formulation Example 2) was sprayed on third leaf stage seedlings of paddy rice (variety: Asahi) grown in soil in a clay pot with a diameter of 9c+n in a greenhouse. Then - at night, under greenhouse conditions (humidity 95-100%, temperature 24-2
5℃), and one day after spraying, rice blast fungus (Plr
A spore suspension of Viricularia oryzae was inoculated by spraying. Contact f! After 15 days, the number of rice blast lesions per leaf on the third leaf was investigated.
The control value (%) was calculated using the following formula.

This test was conducted in triplicate per chemical solution concentration, and the average control value (%) was determined. The results are shown in Table 2.

Control value (*) = On the other hand, regarding chemical damage, the degree of growth, deterioration of leaves, etc. were investigated by visual observation, and the results were expressed according to the following criteria.

O: No chemical damage, 1: Slight, 2: Medium, 3: Heavy, 4: Severe, 5:
The main mortality test was conducted in triplicate for each chemical treatment.

The results are shown in Table 2.

2) Wheat rot disease control test Wheat seedlings (variety, Norin No. 61) in the first leaf stage that were cultivated in soil in clay pots with a diameter of 9 cI11 in a greenhouse.
A predetermined concentration diluted solution of a hydrating powder prepared according to Reference Formulation Example 2) was sprayed in an amount of 20IIIJZ per three pots. One day later, the summer spores of the wheat rot fungus (Puccinia recondita) that had been formed on the wheat leaves were exposed to Tween 20 using a microscope at 150x magnification so that the spore concentration was approximately 50 per field of view.
[Product name of polyoxyethylene sorbitan monolaurate manufactured by Kao Stone f11@] It was suspended in sterile water to which 50 ppm was added, and the spore suspension was sprayed and inoculated onto the leaves to be treated. - After being kept in a greenhouse at 20°C at night, the seeds were placed in a greenhouse at 20°C to promote disease onset. Contact f! After 110 days, the leaves were taken out, the number of diseased diaspores per leaf was investigated, and the control value (%) was calculated using the following formula. The test is 3 per leaf fluid concentration.
It was conducted in a pot system and the average control value was determined. In addition, the degree of drug damage to wheat was investigated using the same criteria as in Test Example 1 and displayed. The results are shown in Table 2.

2nd Table 77 J: (1-CsllyO)2'l:5C
Ht(?δ (commercially available agent, - several names: IBP) Patent applicant Hokuko Chemical Industry Co., Ltd.

Claims (1)

[Claims] General formula▲ Numerical formula, chemical formula, table, etc.▼ (In the formula, R is a cycloalkyl group, a cycloalkylalkyl group, an aryl group, or an arylalkyl group.
Aryl means a benzene nucleus, a pyridine nucleus, a thiophene nucleus or a furan nucleus, which nuclei may be substituted with up to two identical or different halogen atoms, lower alkyl groups or lower haloalkyl groups) , A is ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ groups, ▲ There are mathematical formulas, chemical formulas, tables, etc. ▼ groups or ▲ Numerical formulas, chemical formulas,
There are tables, etc. ▼ indicates a group, and B indicates an alkylene group with a carbon chain of 3 to 6 which may be substituted with a lower alkyl group, but when R is an unsubstituted benzene ring, A is a ▲ mathematical formula, chemical formula, Cyclic acyl hydroxylamine derivatives shown by ▼ (never a group).