JPS61106562A - N-substituted-1,3-benzoxazine derivatives and agricultural and horticultural fungicides - Google Patents

Abstract

(57) [Summary] This bulletin contains application data before electronic filing, so abstract data is not recorded.

Description

Detailed Description of the Invention A) Purpose of the Invention (Field of Industrial Application) The present invention relates to a novel N-substituted-1,3-benzoxazine derivative, which is useful as a fungicide for agriculture and horticulture. .

(Prior art) The N-substituted-1,3-benzoxazine derivative which is the compound of the present invention, more specifically, the N-substituted pensoyl-3,
Compounds similar to 4-dihydro-2H-1,3-benzoxazine derivatives include N1) 1-benzoyl, N-chlorobenzoyl and N-nitrohenzoyl-3,4-
'; It has been described that human O-2H-1,3-benzoxazine derivatives have activity as industrial fungicides. Also, in Belgian patent No. 749676, N
- Although it is stated that henzoyl, N-chlorobenzoyl and N-nitrobenzoyl-3,4-dihydro-2H-1,3-benzoxazine derivatives have activity as plant fungicides, there are no specific There is no description of the degree of activity.

(Problems to be solved by the invention) Conventional N-substituted-1,3-benzoxazine derivatives are
The present invention provides novel N-substituted-1,3-benzoxazine derivatives that are highly practical as agricultural and horticultural fungicides, as well as agricultural and horticultural fungicides, which are highly practical as agricultural and horticultural fungicides in place of these conventional derivatives. The present invention provides disinfectants for use in

Meanwhile, various compounds have been used as fungicides for agriculture and horticulture, but due to safety issues, it is no longer possible to use strong fungicides containing heavy metals such as mercury. Furthermore, when the same drug is used repeatedly, its effectiveness decreases due to the emergence of resistant bacteria. Regarding agricultural and horticultural fungicides, the creation of a powerful compound with a new structure has been long-awaited.The present invention satisfies these demands and solves the problems faced in the field of agricultural and horticultural fungicides. The purpose is to

g) Structure of the invention (means for solving the problem) As described above, the present inventors have discovered that the conventional N-substitution-1,
In order to develop a new agricultural and horticultural fungicide that can solve the problems faced by 3-benzoxazine derivatives and various agricultural and horticultural fungicides that are already widely used, a large number of N
-Substituted-1,3-benzoxazine derivatives were synthesized and their practicality in the field of agriculture and horticulture was intensively investigated. the result,
General formula [wherein R1 is a lower alkyl group, a lower alkoxy group, or a lower haloalkyl group, and m is 1 or 2]
, R2 is a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group, a carboxyl group, a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a lower alkylthio group, a lower alkylsulfinyl group, or a lower alkylsulfonyl group, and n is an integer from 1 to 3, R3 is a hydrogen atom or a lower alkyl group]
It has been found that H-1,3-benzoxazine derivatives are new compounds that have not been described in any literature, and that the above-mentioned problems can be solved by using these compounds.

Compounds of formula CI) according to the invention can be prepared by the following reaction (a). Compounds in which R3 is hydrogen can also be produced by reaction (b) and reaction (C).

Reaction (a) (#Catalyst) In the general formula (II), R1, m, R2 and 1::1·n have the same meanings as above. These compounds are benzamides, and reactions between corresponding O-hydroxyhensylamine derivatives and benzoyl halides, reactions between N-hydroxymethylbenzamide derivatives and phenols, or reactions between O-hydroxybenzyl alcohol derivatives and benzamides can be obtained by In general formula (m), R3 has the same meaning as above. These compounds can be obtained by known methods for aldehydes.

When reacting the compound of formula [■] with the compound of formula (III) in reaction (a), the reaction may be carried out by mere mixing, but it is usually preferable to use a solvent. Examples of solvents include hydrocarbons such as benzene and toluene, ethers such as ethyl ether and tetrahydrofuran, esters such as methyl acetate and ethyl acetate, ketones such as acetone and methyl imbutyl ketone, and nitriles such as acetonitrile and propionitrile. type, methanol,
Alcohols such as 1-tanol, acids such as acetic acid and propionic acid, amides such as dimethylformamide and dimethylacetamide, and water can be used. Although the reaction may proceed without a catalyst, the reaction is usually accelerated and the reaction time is shortened by using an acid catalyst.Om catalysts include WLs, mineral acids such as hydrochloric acid and phosphoric acid, and methane. Organic acids such as sulfonic acid, para-toluenesulfonic acid, Lewis acids such as boron trifluoride etherate, zinc chloride, tin tetrachloride can be used.
.

The reaction temperature varies depending on the solvent and acid catalyst used, but the reaction is usually carried out between room temperature and the boiling point of the solvent.
The reaction will be completed within 3 hours. After the reaction is complete, add a solvent such as benzene, chloroform, ether or tetrahydrofuran and water, separate the organic layer, and distill off the organic solvent to obtain the desired product. Examples 1 and 2 show a method for producing the compound of the present invention by reaction (a), which allows the following reaction.

Reaction (b) (Acid Catalyst) □ In general formula (IV), R1 and m have the same meanings as above. These compounds are substituted benzamides and can be easily obtained by reaction of the corresponding benzoyl/X-lite's with ammonia. The compound of formula (V) is formaldehyde, and is easily available as a paraformaldehyde compound or an aqueous formalin solution. In general formula (Vl), R2 and n have the same meanings as above. These compounds are phenols and can be easily produced by known reactions.

When the compounds of formulas (IV), [V]' and [■] are reacted by reaction (b), the compound of formula [■] is often obtained by simply mixing and heating the three compounds, but Usually, it is preferable to carry out the reaction using a solvent and an acid catalyst.As a solvent, the same hydrocarbons as in reaction (a), ethers, esters, ketones, nitriles, alcohols,
Acids, amides, water, etc. can be used, and similar mineral acids, organic compounds, and Lewis acids can be used as catalysts.1.1
can. Although the reaction temperature varies depending on the solvent and acid catalyst used, 1 the reaction is usually carried out up to the boiling point of the solvent, and the reaction is completed within 5 hours. 0 where the target is obtained
Example 3-4 shows the method for producing the compound of the present invention by reaction (b).
It was shown to.

Reaction (c) (Rr)m [■] [V] (VI) [■] In the general formula [Q], R1 and m are the same as above, a
:Has a taste. These compounds are substituted benzamide N
- in reacting compounds of formulas (W), (V) and (VI) by O reaction (C) which is a methylolated product and can be easily prepared by the known reaction of the corresponding benzamides with formaldehyde, Although the compound of formula [■] can often be obtained by simply mixing and heating the three compounds, it is usually preferable to carry out the reaction using a solvent and an acid catalyst. As a solvent, the same hydrocarbons as in reaction (a),
Ethers, esters, ketones, nitrites, alcohols, acids, amides, water, etc. can be used, and the same mineral acids, organic acids, and Lewis acids can be used as acid catalysts. The reaction temperature depends on the solvent used and Although it varies depending on the acid catalyst, the reaction is usually carried out up to the boiling point of the solvent, and the reaction is completed within 5 hours. 0. After the reaction is completed, the desired product is obtained by processing in the same manner as reaction (a). 6. (c
) is shown in Example 5. Also, m general formula (I) produced by the same method as in the examples
Representative examples of compounds are shown in Table 1. Note that the compound NO used in Table 1 is also referred to in the following Examples and Test Examples.

To use the compound of the present invention as an agricultural and horticultural fungicide,
The compound of the present invention may be diluted as it is or with a liquid carrier such as water or an organic solvent, or a solid powder or other suitable carrier, and if necessary, auxiliary agents such as wetting agents, spreading agents, dispersing agents, emulsifying agents, and fixing agents may be used. Addition of irrigants, fats, liquids, emulsions,
It can be used in formulations such as sol (flowable) agents, powder agents, DL (driftless) type powder agents, fine granules, and granules. Liquid carriers used in formulation include, for example, water, aromatic hydrocarbons, aliphatic hydrocarbons, alcohols, esters, ketones, and acid amides.

Solvents such as dimethyl sulfoxide can be used.

Examples of solid carriers include mineral powders such as clay, talc, kaolin, bentonite, diatomaceous earth, calcium carbonate, and silicic acid, and organic powders such as wood flour. As adjuvants, nonionic, anionic, cationic, and amphoteric surfactants, ligninsulfonic acid or its salts, gums, aliphatic salts, and glues such as methylcellulose can be used.

Preparations such as wettable powders, solutions and emulsions contain 1 to 9 active ingredients.
It may be contained in an amount of 5% by weight, usually in a range of 2 to 75% by weight.

These formulations are generally diluted with water to a concentration of 0.0001 to 10
Used in % by weight. Powders and granules are generally 0.
Contains 1 to IO% by weight of active ingredient. In addition, concentrated liquids such as oils, emulsions, and sols (flowables) can be used as they are as micro-dose dispersants without being diluted. Furthermore, as a seed disinfectant, a hydrating powder or a powder can be applied directly to crop seeds, or a hydrating powder, a sol, an emulsion, etc. can be diluted with water and the seeds can be immersed.

In addition, when the compound of the present invention is used as a fungicide for agriculture and horticulture,
W Ii II & ? -6L zMJfH! a>～
Yatt i! = can be achieved, and in some cases, synergistic effects can be expected.

Specific examples of the method for formulating the agricultural and horticultural fungicide of the present invention are shown in Examples 6-11, but the present invention is not limited to these Examples. In the Examples, parts refer to weight. Show part.

Example 1 3-(2-methylbenzoyl)-3゜4-dihydro-6-chloro-2H- 1,3-benzoxazine (compound N04-chloro-2
-(2-methylbenzoyl)aminomethylphenol
27.6g, paraformaldehyde 4.5g, paratoluenesulfonic acid 0.5g and benzene 300 m
The fL mixture was heated and benzene was distilled off until no water was azeotropically produced. After cooling, the benzene layer was washed with IN-aqueous sodium hydroxide solution and then with water. After drying over anhydrous sodium sulfate, benzene was distilled off under reduced pressure to obtain 26.2 g of the title compound as pale yellow crystals. Recrystallization from methanol gave white crystals 1 with a melting point of 71-73°C.

Example 22-Methyl-3-(3,5-dimethylbenzoyl)-3,4-dihydro-6-chloro-2H-1,3-benzoxazine (Compound No. 54) 4-chloro-2-(3, 5-dimethylbenzoyl)aminomethylphenol 29.0g, paraacetaldehyde 5.7g, Tetrahydrofuran 100m9. Add 50 m of boron trifluoride etherate to the mixture under water cooling.
After the reaction, benzene and water were added and the organic layer was separated and washed with an aqueous INN sodium hydride solution and then with water. The solvent was distilled off under reduced pressure to obtain 29.0 g of the title compound as a pale yellow oil. When purified by column chromatography, it became a colorless oil with a value of 1101.5891.

Example 3 3-(4-t-butylbenzoyl)-3,4
-dihydro-6-chloro-2H -1,3-benzoxazine (compound No. 29) 4-t
-Butylbenzamide 17. ．． 8g, 4-chlorophenol 12.9g, paraformaldehyde 7.8g
was added and stirred at 40°C for 1 hour. Water and benzene were added to the reaction solution, and the benzene layer was separated and washed with IN aqueous sodium hydroxide solution and then with water. After drying over anhydrous sodium sulfate, benzene was distilled off under reduced pressure to obtain 30.6 g of the title compound as pale yellow crystals. Recrystallization from methanol gives white crystals with a melting point of 99-100.
It showed 5°C.

Example 4 3-(2-)lifluoromethylbenzoyl)
-3,4-dihydro-6,7-dichloro-2H-1,3-benzoxazine (compound No. 50) 70% M acid 200 m, 2-trifluoromethylbenzamide 18.9 g and 3,4-dichlor Mix 16.3 g of phenol with 37% formalin aqueous solution 21
Water and benzene were added to the reaction solution, which was stirred for 20 minutes at room temperature and then for 30 minutes at 40° C., and the benzene layer was separated and washed with a 1N aqueous sodium hydroxide solution and then with water.

After drying over anhydrous sodium chloride, benzene was distilled off under reduced pressure to obtain 32.7 g of the title compound as pale brown crystals. Recrystallization from methanol gave white crystals with a melting point of 124-127°C.

Example 5 3-(4-t-butylbenzoyl)-3,4
-dihydro-6-methylthio- 2H-1,3-benzoxazine (compound No. 39) 4-
t-Butylbenzoylaminomethanol 20.7g, 4
-(Methylthio)phenol 14, Ogt-j and 3.9 g of paraformaldehyde were added and stirred at 30°C for 2 hours. Benzene and water were added to the reaction mixture, the benzene layer was separated, and IN hydroxyl; □ 5＋゛″”＊＊＊, *t
After drying over sodium sulfate, benzene was distilled off under reduced pressure to obtain 30.1 g of the title compound as pale negative colored crystals. Recrystallization from methanol gives white crystals, melting point 120-121.5℃
showed that.

Example 6 Wettable powder Compound No. 1, 20 parts of compound No. 1, 5 parts of polyoxyethylene alkyl 7-aryl ether, 3 parts of lignin sulfone distilled calcium, and 72 parts of diatom were uniformly ground and mixed to produce a water solution containing 20% organic component. get the agent.

Example 7 Emulsion 30 parts of Compound No. 25, 5 parts of xylene and 20 parts of polyoxyethylene alkylaryl ether were uniformly dissolved and mixed to obtain an emulsion containing 30% of the active ingredient.

Example 8 50 parts of oil compound No. 32 and ethyl heptarosolve 5
0 parts are uniformly dissolved and mixed to obtain an oil agent containing 50% of the active ingredient.

Example 9 Sol agent (flowable agent) Compound No. 29 pulverized to 10 JL or less
40 parts of □, 2 parts of lauryl sulfate, 2 parts of sodium alkylnaphthalene sulfonate, 1 part of hydroxypropylcellulose, and 55 parts of water were mixed uniformly to obtain the active ingredient 4.
A sol containing 0% is obtained.

Example 10 Powder Compound No. 49 compound powder 0.5 part, silicic anhydride fine powder 0.5 part, calcium stearate 0.5 part, clay 50 parts and talc 48.5 parts were uniformly mixed and pulverized to obtain an effective powder. A powder containing 1% of the ingredients is obtained.

Example ii Granules Compound No. 13, 3 parts, calcium lignin sulfonate, 1 part, bentonite, 30 parts, and clay, 66 parts, were uniformly mixed and pulverized, water was added, granulated, dried, and then sieved to obtain the active ingredient. Granules containing 3% are obtained.

c) Effects of the Invention The compound of general formula (I) of the present invention has significantly superior bactericidal activity compared to conventionally known compounds. In other words, the compound of the present invention exhibits a control effect against a wide range of plant diseases, but shows particularly high activity against rice blast and cucumber root disease, which is the most important disease in rice cultivation. Since the number of times of treatment is large and the total area covered is enormous, there is a strong desire for a more powerful agent that requires less application from the viewpoint of saving labor and avoiding environmental pollution. Test examples 1-4 show specific examples of the effectiveness and effects of the compound of the present invention, which is considered to greatly contribute to future agriculture because it is highly effective in small amounts and is not toxic to animals or fish.

Test Example 1 Rice blast control effect test A predetermined application of a hydrating powder prepared according to Example 6 to the beginning of the third leaf stage of paddy rice (variety: Asahi) cultivated in soil using the bisque firing method in a greenhouse with a diameter of 9 cm. A concentrated chemical solution was sprayed. After this, the mixture was kept under moist room conditions (humidity 95-100%, temperature 24-25°C) overnight, and the spore rfA suspension was spray-inoculated to the rice blast fungus one day after the spraying. Five days after inoculation, the number of rice blast lesions per third leaf was investigated, and the control value (%) was calculated using the following formula. In addition, chemical damage to rice was investigated using the following indicators.

The test was conducted at one concentration in triplicate, and the average control value was determined.

The results are shown in Table 2. The investigation indicators for drug damage are also used in the following test examples.

Number of blast lesions in non-sprayed area x 100 Investigation index of chemical damage 5: Severe 2: Slightly 4: Extremely low: Only 3: Many 0: None Table 2 Rice blast control effect 1. m-work pressure control value x% Σ
Chestnut grade to 200 10
0 019 200
Too 0riJ, 2”
′°° ”°°.

``Kaderon'' Driving and drinking cloth l Kai n1 row button LQ■
Straightforward 31 200
too 042
200 90
Q43 200
too 044
200 100
Q49 200,
1000 Comparative drug A
200 41 2 Comparative drug B 200 32
1 Comparative drug C200153 Comparative drug D 200 51
2 Comparative drug E 200
21 2 Comparative Drugs 2 ○ Comparative Drug F: o,o-diisopropyl S-benzyl phosphorothiolate (generic name: IBP emulsion) Test Example 2
Test of effect of controlling rice blast disease by low concentration treatment The effect of controlling rice blast disease by low concentration treatment was examined in the same manner as Test Example 1. The results are shown in Table 3.

Table 3 Rice blast control effect by low concentration treatment 43
too 100
98 Comparative drug B 32 11
0 Comparative drug C1500 Comparative drug D 48 32
8 Comparative drug E 8 0
0 Test Example 3 Cucumber and disease control effect test Example 6 was applied to the underside of the leaf of a young cucumber seedling (variety: Sumo Hanshiro) in the first leaf stage, which was cultivated in soil using an unglazed body with a diameter of 9 cm in a greenhouse. 1 of the prescribed concentration drug solution of the hydrating powder prepared according to the same method.
10mJIL was sprayed per pot. One day later, the spores of cucumber and the disease fungus (Pseudoperophospora cubensis), which had been spore-formed on the cucumber leaves in the disease-infection room, were examined using a microscope at 150x magnification, with a spore concentration of 20 to 30 per field of view.
Tween 20 (same as above) 50ppm
The mixture was washed off using a brush in ion-exchanged water to which the drug had been added, and the inoculum was used as an inoculum and sprayed onto the underside of the leaves on which the drug had been sprayed.

! After finishing type A, once kept in a humid room at 20℃ for 24 hours,
The animals were stored in a disease development room in a humid room at 24°C to encourage disease onset. After 6 days of storage, it was taken out, the lesion area ratio was investigated, and the control value (%) was calculated using the following formula. The test was conducted in triplicate at 1 concentration.
The average control value (%) was calculated.

The results are shown in Table 4.

Table 4: Disease control effect on cucumbers, ratio of number of lesions and area in sprayed area
0 too 0200
Zoo 0200
too 047
200 Zoo
050 200
too 0ss
200 96
0 Comparative drug A 200
25 1 Comparative drug B 2
00 13 1 Comparative mulberry agent C2
00382 Comparative drug D 200 43
3 Comparative drug E 200
52 3 Comparative drug G ZO
O850 Untreated area 〇
- (Note) Comparative drug G: Ethylene bis(dithiocarbamic acid) manganese (generic name: maneb hydrating agent) 4 Wheat rot disease control test First leaf stage cultivated in soil in a clay pot with a diameter of 9 cm in a greenhouse A diluted solution of a predetermined concentration of a hydrating powder prepared according to Example 6 was sprayed onto young wheat seedlings (variety: Norin No. 61) in an amount of 20 mJL per 3 pots. One day later, the summer spores of the wheat rot disease that had been formed on the wheat leaves were placed under a microscope with a magnification of 150 times using Tween 20 (polyoxyethylene sorbitan monomer manufactured by Kao Soap ■) so that the spore concentration was approximately 50 per field of view. Laurate (trade name) suspended in sterile water to which 50 ppm was added and sprayed on the chemically sprayed leaves - ;, - Night 20
After being kept in a greenhouse at 20°C, the cells were transferred to a -++-, -u room at 20°C to induce disease onset. The vc seeds were taken out after 10 days, the number of diseased naspores per leaf was investigated, and the control value (
%) was calculated.

The test was conducted using 3 pots at a concentration of 1, and the average control value was determined.

The results are shown in Table 5.

Control value for the number of pediculospores in the sprayed area = (1-) (%) Number of pedicel spores in the non-sprayed area x 100 )□ Table 5 Wheat rot disease control effect 14 too 88
016 Zoo
100 026
too 99 040
too 9
4 0 Comparative drug A 100
32 1 Comparative drug B
100 21 1 Comparative drug C100-452 Comparative drug D 100 47
3 Comparative drug E 100
52 3 Comparative drug G 10
0 82 0 Untreated area
〇 - Test Example 5 Barley powdery mildew control test in a greenhouse with a diameter of 9 cm
A predetermined concentration solution of a hydrating powder prepared according to Example 6 was sprayed onto the beginning of the first leaf stage of barley (variety: Azuma Golden) cultivated in soil in a clay pot with a size of 100 ml, and the device was heated at night. After that, a powdery mildew spore suspension was spray inoculated. Seven days after inoculation, the lesion area ratio (%) of barley powdery mildew was investigated, and the control value (%) was calculated using the following formula. The results are shown in Table 6.

(%) Percentage of lesion area in non-sprayed area x 100 Table 16 Table 1: Powdery mildew control effect on barley;
Blood-drinking meng yang engineering wang han han dan y haze comparison drug A 100 18
1 Comparative drug B 100
9 1 Comparative drug C100362 Comparative drug D 100 41
3 Comparative drug E too
49 3 Comparative drug H100870 Untreated group -〇 -(Note) Comparative drug H Nidithiocharcoal is, 5-8-methylquinoxaline-
2,3-diyl

Claims (1)

[Claims] 1) General formula ▲ Numerical formula, chemical formula, table, etc. ▼ [In the formula, R_1 is a lower alkyl group, lower alkoxy group, or lower haloalkyl group, m is 1 or 2, and R_2 is a halogen atom, a lower alkyl group, a lower alkoxy group, a nitro group, a carboxyl group, a lower alkylcarbonyl group, a lower alkoxycarbonyl group, a lower alkylthio group, a lower alkylsulfinyl group, or a lower alkylsulfonyl group, and n is from 1 to 3. an integer, and R_3 is a hydrogen atom or a lower alkyl group], an N-substituted-1,3-benzoxazine derivative. 2) General formula▲ Numerical formula, chemical formula, table, etc.▼ [In the formula, R_1 is a lower alkyl group, lower alkoxy group, or lower haloalkyl group, m is 1 or 2, and R_2 is a halogen atom or a lower alkyl group. , lower alkoxy group, nitro group, carboxyl group, lower alkylcarbonyl group, lower alkoxycarbonyl group, lower alkylthio group, lower alkylsulfinyl group or lower alkylsulfonyl group, n is an integer from 1 to 3, and R_3 is 1. An agricultural and horticultural fungicide characterized by containing as an active ingredient an N-substituted-1,3-benzoxazine derivative represented by a hydrogen atom or a lower alkyl group.