JPH0253773A - Heterocyclic compound and germicide containing same compound as active ingredient - Google Patents

Abstract

NEW MATERIAL:A heterocyclic compound of formula I (R is 3-6C alkyl which may be substituted with an alkyl or alkoxy or cycloalkyl, cycloalkenyl or benzyl which may be substituted with an alkyl or with an O or S at a C atom constituting the ring; Y is H or F; m is 1 or 2; n is 0 or 1; the dotted line is a double bond which may be saturated). EXAMPLE:N-Cyclohexyl-4-(p-t-butylphenyl)-2,5,6-tetrahydropyridine. USE:A germicide having a wide germicidal spectrum and exhibiting remarkable effects against plant disease damages caused by various pathogenic fungi. PREPARATION:A compound of formula III or IV obtained from a compound of II (X is Cl or Br) by the ordinary method is reacted with a compound of formula V to provide a compound of formula VI, which is subjected to a dehydration, fluorination or hydrogenation reaction to provide the compound of formula I.

Description

DETAILED DESCRIPTION OF THE INVENTION <Industrial Application Field> The present invention relates to a novel protocyclic compound and a fungicide characterized by containing it as an active ingredient.

<Prior art and problems to be solved by the invention> Various compounds have heretofore been used as fungicides. However, these compounds require high dosages to achieve sufficient efficacy, show high activity when used prophylactically but do not show sufficient effect when used therapeutically, and have a narrow bactericidal spectrum. There was a problem. Furthermore, even with drugs that have previously shown excellent bactericidal activity, drug-resistant bacteria are becoming more prevalent.
There are some that are no longer able to provide sufficient pest control effects.

It is described in JP-A-62-277858 that certain heterocyclic compounds have bactericidal activity. However, these compounds cannot necessarily be said to be sufficient in terms of their bactericidal efficacy and bactericidal spectrum.

Means for Solving the Problems In view of this situation, the present inventors conducted various studies to develop a compound with excellent bactericidal activity, and as a result, a heterocyclic compound represented by the following general formula [I] was found. It was discovered that it has excellent bactericidal activity, leading to the present invention.

That is, the present invention represents the general formula or 1, and the dotted line represents a double bond that may be saturated. ] Heterocyclic compound represented by (hereinafter referred to as the compound of the present invention)
and a bactericide containing the same as an active ingredient.

Examples of methods for producing the compounds of the present invention include the following methods.

Law.

General Formula [In the formula, R may be substituted with an alkyl group or an alkoxy group, or may be substituted with an alkyl group or an alkyl group, and the carbon atom moiety constituting the ring is an oxygen atom or a sulfur atom. Optionally substituted cycloal [wherein, X represents a chlorine atom, a bromine atom, or an iodine atom]; ] Express the general formula from the compound shown by a conventional method, m
represents 1 or 2, n is 0c, and X has the same meaning as above. ] or the compound represented by the formula is obtained, and the obtained compound represented by the general formula Wataru or the compound represented by the formula avl is combined with the formula [wherein R represents the same meaning as above. ] In the general formula (general formula CI), Y
represents a hydrogen atom and n represents 1.

A method of hydrogenating a compound represented by the general formula □□□.

Production method ■ General formula [In engineering J, Y represents hydrogen doson, n is 1
Method for obtaining a compound represented by the general formula: In the general formula, R has the same meaning as above. ] A method of obtaining a compound of interest by dehydrating the obtained compound of general formula (capital).

Manufacturing method ■ A method for obtaining a compound in which Y represents a fluorine atom and n represents 1 in the general formula [E].

A method of fluorinating a compound represented by the general formula (capital).

Manufacturing method ■ A method of hydrogenating the compound shown in

When producing a compound of the general formula Y from a compound represented by the general formula (capital) in the method (2) above, a solvent is usually used, and examples of the solvent used include ethers such as diethyl ether, tetrahydrofuran, and dioxane. For 1 mole of the compound represented by the general formula (3),
Metallic magnesium is used in an amount of 0.1 to 10 mol, preferably 0.6 to 1.5 mol. The reaction temperature is -20℃~
The temperature is 200°C, preferably 00 to 150°C, and the reaction time is 5 minutes to 50 hours, preferably 10 minutes to 5 hours.

When producing a compound of general formula (4) from a compound of general formula (4), a solvent is usually used, and examples of the solvent used include ethers such as diethyl ether, tetrahydrofuran, and dioxane. The amount of metal lithium or alkyl lithium compound such as n-butyllithium is 0.1 to 10 mol relative to the compound represented by general formula (3),
Preferably it is used in an amount of 0.5 to 1.1 mol. The reaction temperature is -100°C to 200°C, preferably -70°C to 100°C
The reaction time is 6 minutes to 60 hours, preferably 10 minutes to 5 hours.

When producing a compound represented by the general formula example by reacting a compound of general formula Wataru or general formula Jun with a compound of general formula (■),
Usually, a solvent is used, and examples of the solvent used include ethers such as diethyl ether, tetrahydrofuran, and dioxane, aromatic hydrocarbons such as benzene, toluene, and xylene, and mixed solvents thereof. The amount of the compound represented by the general formula K per 1 mole of the compound represented by the general formula Yen or the general formula II is 041 to 10 moles, preferably 0.5
~2 moles are used. The reaction temperature is -70℃~200℃,
Preferably -20°C to 100°C, reaction time 6 minutes to 60°C
The time is preferably 10 minutes to 6 hours. After the reaction is complete,
The compound represented by the general formula can be produced by making it neutral or basic and carrying out usual post-treatments such as extraction, concentration, and if necessary chromatography and distillation.

When producing the compound of the present invention by dehydrating the compound represented by the general formula ry11, a solvent is not necessarily required, but when a solvent is used, ethers such as diethyl ether, tetrahydrofuran, and dioxane, benzene, Aromatic compounds such as toluene, xylene, and chlorobenzene, halogenated hydrocarbons such as methylene chloride, chloroform, and dichloroethane, esters such as methyl acetate and ethyl acetate, pyridine, and the like, or a heated solvent thereof are used. Dehydrating agents include Lewis acids such as trifluoroboron etherate, acid chlorides such as phosphorus oxychloride, and thionyl chloride;
Acids such as sulfuric acid, salts such as potassium hydrogen sulfate, Al, and the like can be used. The dehydrating agent can be used in an amount of 0.0001 mol to 100 mol, preferably 0.01 to 20 mol, per 1 mol of the compound represented by the general formula '38. and preferably -80°C to 800°C.

Reaction time m1 is 1 minute to 100 hours, preferably 5 minutes to
It is 50 hours. Furthermore, 1M' aliphatic octagrade amines such as triethylamine can also be used as a reaction aid. After the reaction is completed, the compound of the present invention can be obtained by extraction under neutral or basic conditions, concentration, and if necessary, usual post-treatments such as chromatography and distillation.

In the method (2) above, when producing the compound of the present invention from the compound represented by the general formula αD, a solvent is not necessarily required, but when a solvent is used, halogenated methylene, chloroform, dichloroethane, etc. Hydrocarbons can be used. As the fluorinating agent, hydrofluoric acid, diethylaminosulfur trifluoride, or the like can be used. Compound 1 represented by general formula (b)
The fluorinating agent can be used in an amount of 0.1 to 100 moles, preferably 0.5 to 50 moles. The reaction temperature is -200°C to 800°C, preferably -100°C to 20°C.
The reaction time is 1 minute to 800 hours, preferably 80 minutes to 200 hours. After the reaction is completed, the compound of the present invention can be obtained by extraction and concentration under neutral or basic conditions, and if necessary, usual post-treatments such as chromatography and distillation.

When producing the compound of the present invention by the method (2) above, a solvent is usually used, and the solvents used include alcohols such as methanol and ethanol, aromatic hydrocarbons such as benzene and toluene, esters such as ethyl acetate, Examples include acetic acid, water, etc., or a mixed solvent thereof. In the presence of a conventional catalytic reduction catalyst such as platinum, palladium Raney nickel, etc., the reaction temperature is -20 to 800°C, preferably 0 to 2°C.
00℃, pressure is 1 atm to 500 atm, preferably 1 atm to
Catalytic hydrogenation is performed at 800 atm and reaction time is 5 minutes to 100 hours, preferably 80 minutes to 60 hours, and the reaction solution is extracted as neutral or basic, concentrated, and if necessary, subjected to conventional post-treatments such as chromatography and distillation. The compound of the present invention can be obtained by carrying out the following steps.

Also when producing the compound of the present invention by the method (2) above,
Catalytic hydrogenation can be carried out using a catalyst such as platinum, palladium, or Raney nickel in the same manner as above.

In addition, the compound represented by the general formula concave can be prepared by a conventional method, for example,
It can be synthesized according to schemes z, n, etc. shown below.

Scheme I Scheme ■ When the compound of the present invention is used as an active ingredient of a disinfectant, it may be used as is without adding any other ingredients, but it is usually used in combination with a solid carrier, liquid carrier, surfactant, or other formulation auxiliary. They are mixed and used in formulations such as emulsions, wettable powders, suspensions, powders, and granules. In this case, the content of the active ingredient, the compound of the present invention, in the formulation is 0.1 to 99.9%, preferably 1 to 90%.

The solid carriers mentioned above include kaolin clay, attapulgite clay, bentonite, acid clay, pyrophyllite, talc, diatomaceous earth, calcite, corn cob flour,
Examples include fine powders or granules such as walnut shells, urea, ammonium sulfate, and synthetic hydrous silicon oxide, and liquid carriers include aromatic hydrocarbons such as xylene and methylnaphthalene, alcohols such as isopropanol, ethylene glycol, and cellosolve. , ketones such as acetone, cyclohexanone, and isophorone, vegetable oils such as soybean oil and nut oil, dimethyl sulfoxide, acetonitrile, and water. Surfactants used for emulsification, dispersion, wet layer, etc. include alkyl sulfate ester salts, alkyl (aryl) sulfone 1L dialkyl sulfosuccinates, polyoxyethylene alkyl 7-aryl ether phosphate ester salts, naphthalene sulfone formalin Examples include anionic surfactants such as condensates, nonionic surfactants such as polyoxyethylene alkyl ether, polyoxyethylene polyoxybrobylene block copolymer, sorbitan fatty acid ester, and polyoxyethylene sorbitan fatty acid ester. As formulation aids, lignin sulfonate, alginate, polyvinyl alcohol, gum arabic, CMC (carboxymethyl cellulose), PAP (
acidic isopropyl phosphate) and the like.

When the compound of the present invention is used as an active ingredient of a fungicide, the application amount of the active ingredient is usually 0.1 to 1 per are.
00y, preferably 0.2 to 202%, and when applying emulsions, wettable powders, suspensions, etc. diluted with water, the applied concentration is 0.001 to 0.5%, preferably O ,OO5
~0.2%, and powders, granules, etc. can be applied as is without any dilution.

The compound of the present invention can also be used as a seed disinfectant,
Furthermore, by mixing it with other fungicides, it can be expected to increase the bactericidal efficacy.

Furthermore, it can also be used in combination with insecticides, acaricides, herbicides, nematicides, plant growth regulators, and fertilizers.

The compounds of the present invention exhibit excellent control effects in terms of preventive effects, therapeutic effects, and systemic transfer effects against various plant diseases with low drug toxicity. Plant diseases for which the compound of the present invention has an excellent control effect include rice blast (Pyriculari
a oryzae), sesame leaf blight (Coch 11ob
o lus mlyabeanus), sheath blight (R
hizoc-tonia 5olani), powdery mildew of wheat (Erysiphegraminis f,
sp, hordei, f, sp, trit i
ci), Gibberella zeae
), Rust (Puccinia stri-iform)
is, p, graminis, p, recondi
ta, p, hordei), snow rot (Typhula
sp, , Micronectriella n1v
alis), naked smut (Ustilago triti)
ci, u nuda), slug panicle disease (Tilleti
a caries), Pseudocerco
-sporella herpotrichoides
), Rhyncho-sporium 5e
cal is), leaf blight (Septoria t
ritici), Blight (Leptosphaeria)
nodorum), Canki'/f7) black spot (Dia
portthe citri), scab disease (El si
noefawcetti), fruit rot disease (Penici)
llium digitatum.

P, 1 tal icum), apple monilia disease (S
clerotiniamali), rot disease (Vals
a mali), powdery mildew (Podo-sphaer)
a 1eucotrich), leaf spot disease (Al t
ernar iamali), scab (Venturi)
a 1naequalis), pear scab disease (Vent
uria nashicola, V. pirxna)
, Alternaria kikuchian
a), Gymnospor-angium h
araeanum), peach sclerotid disease (Scleroti)
niacinerea), Cladospor
Phomopalis sp., grape rot (Elsinoe ampelina), late rot disease (G.
romere-11a cingulata), powdery mildew (Unclnula necatorλ rust (P
hakopsora ampelopsidis), Guignaridia bi
dwellii), oyster anthracnose (Gloeospor
ium kaki), deciduous disease (Cercospora
kaki, Myeosphere 11a now
ae ), anthracnose disease of cucurbits (Colletotrich
uxn lagenarium), powdery mildew (Sp-
haerotheca fuliginea), vine blight (Mycosphaere-11a melonis)
), tomato ring spot disease (Alternaria 5o-1
ani), leaf mold (C1adosporiurn f.
ulvum), eggplant brown spot disease (Phomopsis v
exans), powdery mildew (Er-ysip)xe
cichoracearun), cruciferous vegetable black spot (Alternaria 1aponica), white spot disease (Cercospore-11a brassic)
ae), allium rust (Puccinia allii)
χ Soybean purpura (Cercospora 1ciku)
chii), Elsinoe glycinosis
es), Diaporthe ph-aseo
loru+n var, so jae), kidney bean anthracnose (Coll-etotrichum linde)
mthianLIXn), peanut black astringency (M)r
cosphaerel la personatum)
, Cerco-spora arachidi
cola), powdery mildew of pea (Erysiphe)
pisi), potato (If) summer blight (Alter)
-naria 5olani), strawberry powdery mildew (
5phaero-theca humuli), Exobasidium reticulum (Exobasidium reticulum) of tea
latum), Elsinoe 1eucos
pila), Tobacco Red Star Disease (Alternaria)
longipes), powdery mildew (Erysiphe
cichoracearum), anthracnose (Col-e
totrichum tabacum), sugar beet brown spot (Cer-cospora beticola),
Diplocarponrosae of roses
, powdery mildew (Sphaerotheca pann)
osa), chrysanthemum brown spot (Septoria chry)
santhemi-indici), white rust (Puc
cinia horiana), gray mold (Botrytis cinerea) on fence crops, and sclerotium (S
clerotin-ia sclerotiorum)
etc.

<Effects of the Invention> The compound of the present invention has a wide fungicidal spectrum and is highly effective against plant diseases caused by various plant pathogenic bacteria, and therefore can be used for various purposes as an active ingredient of fungicides.

<Example> The present invention will be explained in more detail below using production examples, formulation examples, and test examples.

Production example 1 pt-butylbromobenzene 8? (0,0141
mole) and metal magnesium piece 0.81' (0,0148
mol) was added to 20 ml of anhydrous tetrahydrofuran, and a tetrahydrofuran solution of pt-butylphenylmagnesium bromide was prepared by a conventional method using ethylene bromide as an initiator. The m111 solution was added with N- under reflux.
Cyclohexyl-4-keto-piperidine 2.56 F
(0,0+, 4.1 mol) was added dropwise and aged under reflux for 3 hours. After the reaction, the reaction solution was poured into ice/hydrochloric acid water and extracted twice with 100ml of ethyl acetate. The mixture was combined, washed once with 100 mJ of a saturated aqueous sodium chloride solution, dried over magnesium sulfate, and then poured once under reduced pressure. The residue was subjected to silica gel column chromatography to obtain 0.58F (0,00168 mol) of N-cyclohexyl-4-(pt-butylphenyl)-4-hydroxypiperidine. Then N-cyclohexyl-4-(I)-t-butylphenyl)-4-hydroxypiperidine 0.5 f (0,
Trifluoroboron etherate Q, 5 mJ was dissolved in 5 mJ of methylene chloride and stirred at room temperature.
Added l. After aging for 2 hours, the reaction mixture was poured into water.

10% water fermentation sodium solution 20knJ9noAJ fi
-7': After that, 7 ethyl acetate and 1 ml of methyl were combined, washed once with saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure.

The residue was subjected to silica gel column chromatography, and N
-Cyclohexyl-4-(p-t-butylphenyl)-2.5.6-titrahydrobiridine 0.12 was obtained.

Production example 2 N-cyclohexyl-4-(p-t-butylphenyl)
-2.5.6-titrahydropyridine 0.8f W4f
Fermented ethyl 2 was dissolved in QTnl. Add to this 10% palladium under a nitrogen atmosphere! go. xr& and hydrogenated under 1 atm at room temperature. After hydrogen absorption had ceased, the reaction mixture was filtered through Celite and condensed under reduced pressure. The residue was subjected to silica gel column chromatography, and N-cyclohexyl-4-(1)-t-butylphenyl)-piperidine was extracted with 0.
1 1 f was obtained.

pJJ. Roadside 8 N-cyclohexyl-4-(p-t-butylphenyl)-4-hydroxypiperidine 1i (0.0081
7 mol) was dissolved in anhydrous methylene chloride iomj and cooled using a dry ice acetone bath under a nitrogen atmosphere.

This solution contains 0 jethylaminosulfur trifluoride.
．． 5ip (0.00817 mol) was added at -70<0>C. The reaction mixture was aged overnight and poured into ice water. Add 20 ml of 10% aqueous sodium hydroxide solution and add 10 ml of ethyl acetate.
The organic layer was washed once with 100 mj of a saturated aqueous sodium chloride solution and concentrated under reduced pressure.

The residue was subjected to silica gel chromatography, and N-cyclohexyl-4-(p-t-butylphenyl)-4-fluoropiperidine was purified. I got 1 2 9.

Table 1 shows some of the compounds of the present invention obtained by such a production method.

Table 1 shows examples of formulations. Note that parts represent 1 part by weight, and the test compounds are shown by compound numbers in Table 1.

Formulation Example 1 Compound of the present invention (050 parts, calcium lignin sulfonate 8 parts, sodium lauryl sulfate 2 parts Formulation Example 2 Compound of the present invention (1) 25 parts, polyoxyethylene sorbitan monooleate 8 parts, CMCa part and water 69 parts are mixed and wet-milled until the particle size of the active ingredient is 5 microns or less to obtain a suspension.

Formulation Example 8 Two parts of the compound (2) of the present invention, 87 parts of kaolin clay and 10 parts of talc are thoroughly ground and mixed to obtain a powder.

Formulation Example 4 20 parts of the compound of the present invention (1), 14 parts of polyoxyethylene steryl phenyl ether, 6 parts of calcium dodecylbenzenesulfonate, and 60 parts of xylene are thoroughly mixed to obtain an emulsion.

Formulation Example 6 2 parts of the compound of the present invention (2), 1 part of synthetic hydrous silicon oxide, 2 parts of calcium lignosulfonate, 80 parts of bentonite and 65 parts of kaolin clay were thoroughly ground and mixed, water was added and the mixture was thoroughly kneaded. The granules are dried to obtain granules.

Next, test examples will show that the compounds of the present invention are useful as fungicides. The compounds of the present invention are indicated by the compound numbers in Table 1, and the compounds used for comparison are indicated by the compound symbols in Table 2.

Table 2 The control efficacy is determined by visually observing the disease state of the test plants at the time of investigation, that is, the bacterial flora on leaves, stems, etc., and the extent of lesions. If about 10 copies are accepted, it is r4J, and if about 60 copies are accepted, it is r8J, 50
If it is found to be about 70 parts, it is given a "1", and if it is found to be about 70 parts, it is given a "1", and if there is no difference from the disease onset condition when no compound is tested, it is given a "0", and it is divided into 6 stages. evaluated and indicated as 5.4.8.2.1.0, respectively.

Test Example 1 Wheat powdery mildew control test (therapeutic effect) A plastic pot was filled with sandy loam, and wheat (Norin No. 78) was grown in a greenhouse for one day. Wheat seedlings that had developed their second leaves were sprayed with five spores of wheat powdery mildew and inoculated.

After inoculation, the test compound was grown in a greenhouse at 28° C. for 8 days and made into an emulsion according to Formulation Example 4. The test compound was diluted with water to a predetermined concentration and sprayed on the leaves so as to sufficiently adhere to the leaf surface. After spraying, 2
The plants were grown in a greenhouse at 8°C for 6 days to examine their pesticidal efficacy. The results are shown in Table ji2.

Table Test Example 2 Wheat powdery mildew control test (preventive effect) Fill plastic pots with sandy loam and grow wheat (Norin No. 78)
were sown and grown in a greenhouse for 10 days.

A test compound prepared as a hydrating agent according to Formulation Example 1 was diluted with water to a desired attitude to a young wheat seedling with f82 leaves developed, and was sprayed on the foliage so that it would sufficiently adhere to the leaf surface. After spraying, spores of wheat powdery mildew were sprinkled and inoculated. After being plated, they were grown in a greenhouse at 28°C for 7 days, and their pesticidal efficacy was investigated.

The results are shown in Table 8.

Claims (2)

[Claims] (1) General formula ▲ Numerical formulas, chemical formulas, tables, etc. represents a cycloalkyl group, cycloalkenyl group, or benzyl group in which the carbon atom moiety constituting may be substituted with an oxygen atom or a sulfur atom, Y represents a hydrogen atom or a fluorine atom, and m
represents 1 or 2, n represents 0 or 1, and the dotted line represents a double bond that may be saturated. ] A heterocyclic compound represented by (2) A disinfectant characterized by containing the heterocyclic compound according to claim 1 as an active ingredient.