JPH04108774A - Optically active n-indanylnicotinic acid amide derivative and agricultural and horticultural fungicide comprising the same derivative as active ingredient - Google Patents

Abstract

NEW MATERIAL:N-[(3R')-1,1,3-Trimethyl-4-indanyl]-2-chloronicotinic acid shown by formula I. USE:An agricultural and horticultural fungicide. PREPARATION:N-(1,1,3-Trimethyl-4-indanyl)-nicotinic acid amide shown by formula II is subjected to optical resolution by using a column for separating optical isomers to give a compound shown by formula I. Or, carboxylic acid shown by formula III or a derivative thereof is made to react with (3R)-1,1,3- trimethyl-4-aminoindane shown by formula IV preferably at -40 deg.C to the boiling point of the used solvent to give the compound shown by formula I.

Description

[Detailed Description of the Invention] [Industrial Application Field] The present invention relates to an optically active N-indanylnicotinamide derivative and an agricultural and horticultural fungicide containing the same as an active ingredient.
Specifically, the present invention relates to N-[: (3R) -1,1°3-trimethyl-4-indanyl-2-chloronicotinamide and an agricultural and horticultural fungicide containing the same as an active ingredient.

[Prior Art and Problems to be Solved by the Invention] It has been known that certain carboxylic acid amide derivatives have biological activities such as bactericidal effects.

For example, the following compounds have been confirmed to have bactericidal activity.

However, as is clear from the test examples described below, the above-mentioned compounds cannot necessarily be said to have sufficient efficacy as agricultural and horticultural fungicides.

Also, benomyl [methyl-1-(butylcarbamoyl)]
Benzimidazole-thiophanate fungicides such as benzimidazole-2-ylbamate] and thiophanate methyl J1,2-bis(3-methoxycarbonyl-2-thioureido)benzene are effective against various pathogenic bacteria that infect agricultural and horticultural crops. 19 shows excellent pesticidal effect.
It has been widely used as an agricultural and horticultural fungicide since the 1970s. However, pathogenic bacteria that are resistant to these disinfectants (hereinafter referred to as "drug-resistant bacteria") have become widespread, and a situation has arisen in which they are virtually impossible to use.

Procymidone [N-'(3,5-dichlorophenyl)
Cyclic imide fungicides such as 1,2-dimethylcyclopropane-1,2-dicarboximide] have been widely used in place of the above-mentioned fungicides because they have shown activity against these drug-resistant botrytis fungi. However, in recent years, pathogenic bacteria that are resistant to such cyclic imide fungicides have become widespread, and situations have often arisen where they are virtually impossible to use.

It has been reported that N-phenyl carbamate compounds described in JP-A-58-126856 and the like exhibit high activity against such resistant bacteria.

However, N-phenyl carbamate compounds are
It may not be used alone because it has no effect on drug-sensitive bacteria.

[Means to solve the problem]

In view of the above-mentioned problems, the present inventors have previously discovered that specific N-indanylcarboxylic acid amide derivatives have excellent bactericidal activity (Japanese Patent Application Laid-Open No. 34962/1996 and Japanese Patent Application No. 23511/1983). As a result of further intensive studies on these compounds, we have discovered a compound that has a strong bactericidal effect on both drug-susceptible and drug-resistant bacteria, leading to the completion of the present invention.

That is, the present invention provides an optically active N-indanylnicotinic acid amide derivative represented by the following formula [■] and an agricultural and horticultural fungicide containing the same as an active ingredient.

The present invention will be explained in detail below.

The compound of the present invention is a new compound, for example, by optically resolving N-(1,1,3-trimethyl-4-indanyl)-nicotinamide represented by the formula using an optical isomer separation column. Obtainable.

In addition, the compound of the present invention can be prepared according to the following reaction formula [:II
I] (IV) [I) The above reaction is carried out between a carboxylic acid represented by formula [■] or a reactive derivative thereof and a reaction mixture represented by formula (IV) (3R) in the presence or absence of a reaction-inert solvent. )-1,1,3-trimethyl-4-aminoindan.

The carboxylic acid represented by the above formula CI[I] or its reactive derivative is (3R)-i represented by the formula [], 1.
0.5 to 3-trimethyl-4-aminoindan
It is used in a range of 1.5 equivalents, preferably in a range of 0.9 to 1.5 equivalents.

The above reaction can be carried out in a temperature range from -70°C to the boiling point of the solvent used, preferably in a temperature range from -40°C to the boiling point of the solvent.
Examples of reactive derivatives of carboxylic acids represented by the above include corresponding acid anhydrides, acid halides such as acid chlorides, and carboxylic acid esters.

Examples of solvents used in the reaction include aromatic hydrocarbons such as benzene and toluene; halogenated hydrocarbons such as carbon tetrachloride and chloroform; aromatic halogenated hydrocarbons such as chlorobenzene; diethyl ether and tetrahydrofuran. , ethers such as dioxane; esters such as ethyl acetate; polar solvents such as dimethyl sulfoxide, dimethylformamide, and water.

In order to make this reaction proceed smoothly, the following suitable reaction aids can be used depending on the type of carboxylic acid represented by the general formula [■] or its reactive derivative.

When a carboxylic acid is used, a dehydrating agent such as ethoxyacetylene, cyclohexylcarfodiimide, or phosphorus pentoxide is used; when an acid anhydride is used, a tertiary amine such as N-methylmorpholine or triethylamine, pyridine,
When using aromatic bases such as picoline, N,N-diethylaniline, acid halides, tertiary amines such as triethylamine; aromatic bases such as pyridine and picoline; sodium hydroxide, potassium hydroxide; alkali metal hydroxides such as sodium hydroxide; or alkali metal alcoholades such as sodium ethylate; and when using carboxylic acid esters, alkali metal alcoholades such as sodium ethylate. etc. can be used.

These reaction aids are represented by the formula [Iff] (3R)
It can be used generally in an amount of 0.01 to 2.0 equivalents, preferably in a range of 0.9 to 1.1 equivalents, relative to -1,1,3-)trimethyl-4-aminoindan.

Note that (3R)-1,1,3-) represented by formula (IV)
-Thumethyl-4-aminoindan can be obtained by the following method.

i) A method of optically resolving 1.1.3-trimethyl-4-aminoindan using an optically active carboxylic acid.

1j) A method for optically resolving l,L3-trimethyl-4-aminoindan using an optical resolution column.

Furthermore, the compound of the present invention can also be produced according to the following reaction formula.

[I]

The above reaction involves 1-acyl-(4R) represented by the formula [■]
-I, 2.3.4~Tetrahydro-2,2,4-trimethylquinoline derivative in the presence of an acid catalyst, -40 °C ~ 2
It is carried out by rearrangement at 00°C, preferably 0°C to 150°C.

Examples of the acid catalyst include sulfuric acid, phosphoric acid, polyphosphoric acid, Lewis acid, etc., and the amount thereof can be from 0,001 equivalent to a large excess relative to the above-mentioned acyltetrahydroquinoline derivative.

The compound of the present invention thus obtained is a novel substance and has excellent bactericidal activity. In particular, it has excellent control power against various plant pathogens and is useful as a fungicide for agriculture and horticulture.

When using the compound of the present invention as an agricultural and horticultural fungicide, it may be used as it is, but in order to effectively disperse the active ingredient at the time of application, an adjuvant may be added according to a conventional method. It is preferable to use it in the form of , emulsion, wettable powder, powder, or the like.

Examples of solvents that can be used as auxiliary agents include water, alcohols (methyl alcohol, ethyl alcohol, ethylene glycol, etc.), ketones (acetone, methyl ethyl ketone, cyclohexanone, etc.), and ethers (
ethyl ether, dioxane, cellosolves, etc.), aliphatic hydrocarbons (kerosene, kerosene, fuel oil, etc.), aromatic hydrocarbons (benzene, toluene, xylene, solvent naphtha, methylnaphthalene, etc.), halogenated hydrocarbons (dichloroethane, trichlorobenzene, carbon tetrachloride, etc.), acid amides (dimethylformamide, etc.), esters (ethyl acetate, butyl acetate, glycerin esters of fatty acids, etc.), nitriles (acetonitrile, etc.), etc. are suitable. One or a mixture of two or more of these may be used.

In addition, as fillers, mineral powders such as clays such as kaolin and bentonite, talcs such as talc and pyrophyllite, oxides such as diatomaceous earth and white carbon, and plants such as soybean powder and carboxymethyl cellulose (CMC) are used. suitable powders, and one or a mixture of two or more of these may be used.

Additionally, surfactants may be used as spreading agents, dispersants, emulsifiers, and penetrants.

Examples of the above surfactants include nonionic surfactants (polyoxyethylene alkyl allyl ether, polyoxyethylene sorbitan monolaurate, etc.), cationic surfactants (alkyldimethylbenzylammonium chloride, alkylpyridinium chloride, etc.) )
, anionic surfactants (alkylbenzene sulfonates, lignin sulfonates, higher alcohol sulfates),
Examples include amphoteric surfactants (alkyldimethylbetaine, dodecylaminoethylglycine, etc.). These surfactants are used singly or as a mixture of two or more depending on the purpose.

When applying the agricultural and horticultural fungicide of the present invention in the form of an emulsion, 10 to 50 parts of the compound of the present invention and 10 parts of a solvent are used.
80 parts of surfactant and 3 to 20 parts of surfactant are mixed to form a stock solution, which is diluted with water to a predetermined concentration before use and applied by a method such as spraying.

In addition, when used in the form of a wettable powder, the compound of the present invention 5
A mixture of ~80 parts of emulsion, 10 to 90 parts of an extender, and 1 to 20 parts of a surfactant is diluted with water or the like in the same manner as in the case of the emulsion.

When used in the form of a powder, it is usually a mixture of 1 to 5 parts of the compound of the present invention and 95 to 99 parts of a filler such as kaolin, bentonite, or talc.

Furthermore, the agricultural and horticultural fungicide of the present invention can also be used in combination with other active ingredients that do not inhibit the fungicidal effect of the active ingredient, such as fungicides, insecticides, acaricides, etc.

The method of applying the agricultural and horticultural fungicide of the present invention can be suitably applied to both foliage spraying and water surface application.

For foliage spraying, the emulsion or hydrating agent is usually applied at a rate of 10 to 1
It may be diluted with water to contain 1000 pp, and applied in an amount of 10 to 5001 per 1O are.

〔Example〕

Next, the present invention will be described in more detail with reference to Examples, but the present invention is not limited to the following Examples unless it exceeds the gist thereof.

Note that "parts" below indicate "parts by weight."

Furthermore, the structures of the compounds of the present invention synthesized in the production examples were confirmed by elemental analysis, IR spectrum, NMR spectrum, X-ray analysis, and the like.

Moreover, optical purity was calculated using HPLC for optical isomer separation.

Production Example 1 Synthesis of N-[(3R)-1,1,3-4limethyl-4-indanyl]-2-chloronicotinic acid amide 1.1.3-Trimethyl-4-aminoindan (233
g) and l-tartaric acid (100 g) in methanol (200 m
L) and heated under reflux for 2 hours.

Next, the mixture was allowed to cool to room temperature, and the crystallized salt was collected by filtration, and recrystallized with methanol three more times.

The obtained salt was made alkaline with an aqueous sodium hydroxide solution, extracted with ether, and concentrated to give (3R)-1,1,3
-Trimethyl-4-aminoindan (40g) was obtained.

The physical property values were as follows.

Optical purity -96%ee [α]" = -33,4° (C = 1.21., C
HI 3) The above (3R)-1,1,3-trimethyl-
4-aminoindan (4g, 96%ee) and pyridine (
2-chloronicotinic acid chloride (6.0 g) was added to a mixed solution of 2-chloronicotinic acid chloride (3.6 g) with ethyl acetate (200 mL) under water cooling.
) was added and reacted overnight at room temperature.

Water and ethyl acetate were added to the resulting reaction solution to separate the layers, the organic phase was washed with brine and dried with sodium sulfate, and the resulting residue was subjected to silica gel column chromatography (developing solution: n-hexane: ethyl acetate). = 1:2), N
-[(3R)-1,1°3-trimethyl-4-indanyl]-2-chloronicotinic acid amide (6.5 g) was obtained.

The physical property values were as follows.

Optical purity = 96%ee [α] = -54,9° (C = 1.20. CHC
j73) The above N-nicotinic acid amide was an amorphous solid and difficult to crystallize, so the previously obtained (3R)
-1,1,3-trimethyl-4-aminoindan 4-
X-ray crystal structure analysis was performed on the crystal obtained by chlorophenylamidation. As a result, it was revealed that the absolute configuration was R-configuration.

Note that the obtained [(3R)-1,1,3-trimethyl-
The physical properties of 4-aminoindanyl]-4-chlorophenylamide were as follows.

m, p, = 1.58.5-159.56C Production Example 2 Synthesis of N-[:(3R)-1,l,3-)dimethyl-4-indanyl]-2-chloronicotinamide N-( 1,1,3-trimethyl-4-indanyl)-2
- Chloronicotinamide was prepared using a Chiralcel OD optical isomer separation column using hexane and isopropanol (9
: Separated into both mirror bodies using the mobile phase of 1). Target N-[(3R)-1゜1.3-trimethyl-4-indanyl-2-chloronicotinamide (8 bodies, 100
%ee) was eluted as a later peak, and showed the following specific optical intensity.

Formulation Example 1 20 parts of each enantiomer of N-[(3R)-1,1,3-trimethyl-4-indanyl]-2-chloronicotinamide (compound numbers 1 and 2) shown in Table 1 was used. ,
A wettable powder was obtained by uniformly grinding and mixing 75 parts of diatomaceous earth and 5 parts of a surfactant containing alkylbenzenesulfonic acid as a main component.

Each of the compounds shown in Table 2 (compound numbers A-D) was also formulated into a hydrating powder in the same manner as above.
) 1□ 1. 1
Formulation Example 2 40 parts of each enantiomer (compound numbers 1 and 2) of N-C(3R)-1,I,3-trimethyl-4-indanyl]-2-chloronicotinamide shown in Table 1 was added. Use each,
10 parts of white carbon, 47 parts of diatomaceous earth, and 3 parts of "Tsurpol" 5039 (trademark of Toho Chemical Co., Ltd., a surfactant whose main component is polyoxyethylene alkylaryl ether sulfonate) are uniformly ground and mixed to form a wettable powder. Obtained.

Each of the compounds shown in Table 2 (compound numbers A to D) were also formulated into wettable powders in the same manner as above.

Test Example 1 Drug-susceptible cucumber gray mold control effect test Each wettable powder prepared in Formulation Example 1 was diluted with water to a predetermined concentration on cotyledon-stage cucumbers (variety Niyoyoba) grown in pots with a diameter of 6 cm. The mixture was sprayed on foliage at a rate of 10 i per pot.

After the chemical solution was air-dried, a drug-susceptible gray mold fungus (Botrytis cinerea) was spray-inoculated and kept in a greenhouse at 23° C. for 4 days after inoculation to investigate the late-onset disease state. The investigation method was as follows.

That is, the disease severity is determined by calculating the percentage of diseased area of the investigated leaves, and classifying them into indices of 0.1, 3.5, and the number n of leaves corresponding to each disease severity index. +nl+13+n, was investigated and calculated using the following formula (n is the total number of leaves investigated).

The control value was calculated using the following formula.

The results are shown in Table-3.

Table 3 Test Example 2 Drug-resistant cucumber gray mold control effect test Cotyledon stage cucumber seedlings grown in pots with a diameter of 6 cm (variety:
Each of the wettable powders prepared in Formulation Example 1 was diluted with water to a predetermined concentration and sprayed on the leaves at a rate of 10 mJ per pot.

After air-drying the chemical solution, the drug-resistant gray mold fungus (Potrytis
Botrytis cinerea) was spray-inoculated and kept in a greenhouse at 23° C. for 4 days after inoculation to investigate the late-onset disease state. The investigation method was as follows.

That is, after the onset of the disease, the diseased area ratio of the investigated leaves is determined, and the diseased area is classified into indices of 0, ■, and 3.5 according to the severity, and the number n of leaves corresponding to each diseased index is determined. +nl+n3+n, was investigated and calculated using the following formula (n is the total number of leaves investigated).

■ The control value was calculated using the following formula.

The results are shown in Table 4.

Test Example 3 Rice sheath blight control effect test Each wettable powder prepared in Formulation Example 1 was diluted with water to a predetermined concentration on 3- to 4-leaf stage rice (variety Nihonbare) grown in pots with a diameter of 6 mm. The seeds were sprayed on foliage at a rate of IO- per pot.

After the chemical solution was air-dried, a concave suspension of the sheath blight fungus Rhizoctonia solani (R1zoctonia 5olani) cultured in YG medium was spray inoculated, kept in a greenhouse at 29°C for 40 hours, and then left in an aquarium in the greenhouse for 3 days. The severity of the lesions that appeared was measured and the control value was calculated using the following formula.

The results are shown in Table-5.

Test Example 4 Wheat Rust Control Efficacy Test Each wettable powder prepared in Formulation Example 1 was diluted with water to a predetermined concentration on 1- to 2-leaf stage wheat (variety: Norin No. 61) grown in pots with a diameter of 6 cm. The mixture was then sprayed on foliage at a rate of IO- per pot.

After the leaf liquid was air-dried, a spore suspension obtained by grinding wheat infected with the wheat rust fungus (Puccinia recondita) was spray-inoculated, and 220
After being kept in the greenhouse of C for 15 hours, it was left in an aquarium in the greenhouse for 7 days.

For evaluation, the ratio of lesion area on each leaf was assessed and the control value was calculated using the following formula.

The results are shown in Table-6.

〔Effect of the invention〕

The compound of the present invention is a new substance and has excellent bactericidal activity.

Therefore, for example, rice sheath blight (Rhizoctonia S
olani), various rust diseases of wheat (Puccinia
recondita), snow rot (Typhula 1n
carnate, T.

1shikariensis), leaf rot disease of lawns, grasses, etc. (Rbizoctonia 5olani), gray mold disease of various crops (Botrytis cinerea)
), rice blast disease (Pyricularia ory
zae) and powdery mildew (Erysiphe) on various crops.
graminis) and sclerotia of various crops (Soler
It has a strong bactericidal effect against bacteria such as Otinia solerotiorum. Among these, it has extremely high activity against gray mold, both against bacteria that are susceptible to benzimidazole-thiophanate fungicides and cyclic imide fungicides, and against bacteria that are resistant to them. It is useful as a fungicide.

Further, although the compounds of the present invention have permeability to plants, they have almost no harmful effects on plants, and have low toxicity to humans, livestock, and fish, so they are extremely useful for controlling plant diseases.

Claims (2)

[Claims] (1) An optically active N-indanylnicotinamide derivative represented by the following formula [I]. ▲There are mathematical formulas, chemical formulas, tables, etc.▼〔I〕 (2) A fungicide for agriculture and horticulture, which contains the compound according to claim 1 as an active ingredient.