JPS5852256A - Substituted or unsubstituted fatty acid amide derivative and its salt - Google Patents

Abstract

NEW MATERIAL:The compound of formulaI[X is halogen, group of formula IV (R4 is H, lower alkyl or halogen), etc.; R1 is 1-10C alkyl or phenoxy substituted with phenyl, etc.; R2 is H, 1-5C alkyl, allyl, etc.; R3 is 1-8C alkyl, allyl, cycloalkyl, pentylidine, phenyl, etc.]. EXAMPLE:N-2'-Methyl-4'-chlorophenyl-2-( 3-chloro-1,2,4-triazol-1-yl )-2-n-octanamide. USE:Nonmedical bactericide, herbicide or fungicide. PROCESS:The objective compound of e.g. formulaI' can be prepared by reacting the compound of formula III with the compound of formula II in an inert solvent such as benzene, toluene, THF, etc. in the presence of a proper base (e.g. Na2CO3, NaOH, etc.) at -20-+30 deg.C, preferably -10-+10 deg.C.

Description

Detailed Description of the Invention The present invention is directed to a group represented by the general formula (1) (wherein R1 represents a hydrogen atom, a lower alkyl group, or a halogen atom), and R1 has 1 carbon atom. represents an alkyl group having 1 to 10 alkyl groups, a phenyl group, or a phenoxy group substituted with a halogen atom; R1 is an alkyl group having 1 to 8 carbon atoms, an allyl group, a cycloalkyl group, a ventridine group, a lower alkyl group, a lower alkoxy group, a halogen atom, a nitro group, a cyano group, an acetyl group. , trifluoromethyl group, alkoxycarbonyl group or p-methylphenethyloxy group, L represents an integer of 1 to 5, substituted phenyl group, benzyl group, α-substituted penzyl group, represented by the following formula: CH2 ()-(-)m (in the formula, ;zti
)・Represents a logon atom, and m represents an integer from 1 to 2. ), R1 and R1 together with the nitrogen atom form a piperidine ring,
piperidine ring, the following formula: 0(Ry)n (wherein, R7
represents a lower alkyl group, a hydroxycarbonyl group, an alkoxycarbonyl group, or a hahenzil group, and n is 1 to 2.
represents all integers of ), represents a substituted piperidine ring represented by ), represents a hexamethylene atom or a methyl group, represents an ion represented by ) or a trifluoromethyl group; ) represents a piperazine/ring represented by 1 (in the formula, R1g+ represents a hydrogen atom or a halogen atom). ] The present invention relates to fatty acid amide derivatives and salts thereof.

The compound represented by the general formula (1) of the present invention is a novel compound that has not been described in any literature, and is useful as a non-medical fungicide, herbicide, or antifungal agent.

The compound vIJ represented by the general formula (1) can be synthesized, for example, by the method shown schematically below.

(Clear (When X is a halogen atom) <IY
(IF (in the formula, R11Rle R4 and It can be synthesized by reacting the compound represented by formula (II) in a completely inert solvent in the presence of an appropriate base. Since this reaction is exothermic, the reaction temperature is, for example, -20°C. ℃~30℃, preferred tt, <u-1
It is preferable to set the temperature within the range of 0°C to 10°C.

By reacting a compound represented by the general formula (17 (when X is an azole) ii, a compound represented by the general formula (I)' and an azole in an inert solvent in the presence of an appropriate base, Can be synthesized.

The compound of general formula (1)'' can also be collected as a salt of an inorganic acid such as hydrochloric acid or sulfuric acid, or an organic acid such as acetic acid or oxalic acid. Preferably, the temperature is set from room temperature to about 100°C.

All of these reactions are equimolar reactions, so use of reactants! #'i It may be determined based on common sense; for example, it is also possible to use either reactant in slightly excess.

The inert solvent used here may be one that does not significantly inhibit the progress of this type of reaction, such as aromatic hydrocarbons such as evabenzene, toluene, and xylene; ethers such as ethyl ether, tetrahydrofuran, and dioxane. Ketones such as acetone, methyl ethyl ketone, and cyclohexanone; Lower fatty acid Nisdels such as ethyl acetate; Lower fatty acid amides such as dimethylamide and dimethylacetamide; dimethyl sulfoxide, pyridine, and the like.

These may be used alone or in mixtures.

Optionally, it is also possible to use water or a mixture of water and the abovementioned solvents.

Examples of the base that can be used in this reaction include sodium hydroxide, sodium carbonate, sodium hydroxide, potassium carbonate, sodium carbonate, sodium hydroxide,
Inorganic bases such as potassium carbonate, hydrogen carbonate, potassium hydrogen carbonate; organic salts such as pyridine, triethylamine, trimethylamine, diethylaniline, -8-diazabicyclo-(5,40)-7-undecene, etc. can.

It is also possible to add an azole as a reactant in an amount that also acts as a base and use it as a base.

After the reaction is completed, the reaction will be produced @ If all conventional methods are used, the objective #11J will be obtained.
For example, a representative compound represented by the general formula (1) can be collected by extracting the target product from the reaction product with an appropriate extraction solvent, drying the extract, and then distilling off the solvent. All examples are shown in Table 1.

Table 1 Next, Table 2 shows NMR spectral data of some compounds.

The compounds of the present invention are useful as non-medical fungicides and are effective against algae, such as rice blast disease (Ptricularia oryzae).
) :Rhizoctonia go 4p4 (Rhizoctonia go
lani): Powdery mildew of barley and wheat (Er)'5tl
) he graminea) and Kie's nine-year-old mildew (31) haerotheea fulginia)
'Podosphaera 1e
ucotricha) and grapevine mildew (Unc
Other cotton rot diseases on various host plants such as P. inula necator;
nia veeondlta) and other rusts, oat crown rust (Pucclnia coronata)
It is extremely effective in controlling V for diseases such as rust and other host plants.

Furthermore, the compound of the present invention is useful as an anti-XtIM agent against various fungi shown below.

Candida albicans
Trieho
sporoneutaneuml, Corsicolor fungus (Co
riolus versieolor), tricode 7y
Tricodermaviridea
), Triehopbyton menta
grop-bytea), Saecharomyces eeerevi
siae), Pichia polymorph y (Pichia
polymorpha), No1senula anomala (Ha
nsenula anomala), Rhodotorula glutinis-
Fenoporua coeine (P)
n+s) sO9 Tyromyces
palugtrim), Chaietomicum globosum (
Chaetominu globosum), Triehophyton rubrum 'h
Candida albicans
canm), Trichopbyton me
ntatroph)'tea) "Trie
hophyton rubrum) and is effective against candidiasis, athlete's foot, and leukocoria.

The compounds of the present invention are also useful as herbicides.

Synthesis examples of the present invention are shown below, but the present invention is not limited thereto.

Synthesis example l N-2'-methy/I/-4'-chlorophenyl 2-(
5-chloro-tλ4-triazol-1-yl)-n-
Synthesis of octanamide (compound 142)
111ODMSOK Dissolve. Add 12 g (α012 mol) of 5-chloro-1,2,4-) lyazole to this solution.
and 8-diazabicyclo-[飄4,0)-7-undecene 18f ((1012 mol) were added, heated to 60°C and stirred for 24 hours, and the target product was extracted from the reaction solution with 100 to 150 mol of ethyl acetate. After extracting with
The target object tMf is obtained as .

δ value/CDC/a 2 (* 2.21 P
B 5 H■ &55yp B IH ■ FLOOP t IH ■ a81pp l IH synthesis example 2 N-mefk-N-4'-fluorophenyl 22-bromooctanoyl chloride 7,3 F ((103 mol) to 200 mJ of ether Dissolve and cool in a cabinet at 0°C.Add N-methyl-4-fluoroaniline tIF to this solution.
((1033 mol) and triethylamine 53t (ao!
+3 mol) is added dropwise with reaction eccentricity at 5°C or below. 0. After the completion of the dropwise addition, the reaction solution is stirred for about 2 hours. 6. After the completion of the reaction, the reaction solution is washed 3 times with 200 d of LIN hydrochloric acid water. death,
After drying and distilling off the ether, the desired product @a7f is obtained.

Refractive index surface: 1.5146 Yield: 88 Synthesis example 5 Synthesis of N-methyz-N-4'-fluorophenyl 2-(imidazol-1-yl)-1-octanamide (compound number 172) N- #fk-N-4'-fluorophenyl 2-bromooctanamide 5f (101 mol) t-20d DM
Dissolve SOKIli, add anhydrous potassium carbonate L7f (101 mol) and imidazole 182 (0012 mol),
The reaction is carried out at 80°C for 1 hour. After the reaction is complete, add 1 part of water to the reaction solution.
00d was added, and the target product was extracted with 1001 Ll of ethyl acetate. After adding 101 ml of concentrated hydrochloric acid to the ethyl acetate solution and transferring the target product to the aqueous layer, this salt M bath solution'f: Nag COs
Neutralize with water, add 100111 ethyl acetate, and extract the target product. After drying, ethyl acetate is distilled off under reduced pressure to obtain 2-3 ft of the desired product.

Refractive index n',j: t5272 Yield: 73%
Synthesis Example 4 Synthesis of N-5', 4'-dichlorophenyl 2-(imidazol-1-yl)octanamide (compound level 1
79) N-3', 4'-dichlorophenyl 2-bromooctanami)-16r (110068 mol) f 5ol
Ll! o Anhydrous potassium carbonate 199 (0014 mol) and imidazole 19/(
α014 mol) was added and the reaction was carried out at 100°C for 2 hours.

After the reaction is complete, add 200ml of water to the reaction solution and add the target object '11.
Extract with 00 m4 of ethyl acetate. Vinegar rice ethyl layer 1zl
After washing twice with OUm/ of water, 200 iu of 3N salt was added, and the target product was dissolved in hydrochloric acid water. After making this hydrochloric acid aqueous solution weakly alkaline with all sodium carbonate, ethyl acetate 100-
Add gold and extract ash. After drying the extract, ethyl acetate is distilled off under reduced pressure to obtain the target product ztr.

Refractive index n', J: t5610 yield = 4: 8
2% Synthesis Example 5 Synthesis of N-methyl-N-(α-methylbenzyl)2-bromooctanamide (compound ml!15) 2-bromooctanoyl chloride? ! A mixture of -42t ((101 mol) dissolved in 100 d of tetrahydrofuran (001 mol) (may be diluted with an appropriate solvent) was added dropwise at below 10°C, and after the dropwise addition, room temperature -('5 After the reaction, tetrahydrofuran was distilled off under reduced pressure, and the reaction product was extracted with 100 ml of ether.
The ether layer was separated, dried over Glauber's salt, and the ether was distilled off under reduced pressure to obtain the target gold 2-73f.

Refractive military cap: t518 Yield: 80 Synthesis Example 6 Synthesis of N-methyl-N-(α-methylbenzyl)2-(1-imidazolyl)-octanamide (Compound 186) N-methyl-N-(α-methyl benzyl) 2-bromooctanamide! Dissolve L40@((101 mol) iloom in dimethylformamide. In the solution, imidazole α7F (0.01 mol) and t8-diazabicyclo-[
翫4,03-7-undecene tstt ((101 mol)
was added, and heated and stirred at 50 to 60°C for 3 hours. After completion of the reaction, dimethylformamide was distilled off under reduced pressure, and the desired product was extracted from the reaction mixture with 10 mL of ethyl acetate, washed several times with 100 mL of water, the ethyl acetate layer was separated, and an aqueous hydrochloric acid solution was added. Then, the target product was transferred and dissolved in an acidic aqueous solution. After making this aqueous solution basic with Na1COs, ethyl acetate +
OQpxe? Add the target substance and extract it with mirabilite iii.
After drying, removing the pressure, adding ethyl acetate to extract the target ant, and drying with sodium sulfate, ethyl acetate was distilled off under reduced pressure to obtain the target ant.
Get 64r.

Refractive index nV; t5286 Yield: 50% Next, one test example and an example are given.

Test Example 1 Barley Powdery Mildew Treatment Efficacy Test Barley grown in a porcelain pot with a diameter of 12 mm was inoculated with powdery mildew fungus t, and one day later, the compound of the present invention 200F as the active ingredient (an aqueous suspension of the emulsion formulated in the example) was inoculated. Spraying was carried out on a turntable using a total of 1 spray gun.

After spraying, the plants were stored in a greenhouse at 25° C. for 7 to 10 days, and then their pest control effects were examined in comparison with untreated plots.

Judgment criteria for pest control effectiveness 4... Control value is 95% or more, 3... Sediment control value is 80% or more and less than 951 2...
- Control value 60% or more and less than 80%' 1... Control value less than 60% The results are shown in Table 3.

- Table 3 Test Example 2 Part 2 of m*Efficacy Test of Wheat Powder Disease 1112s
After inoculating cultivated oats with spores of Cannabis disease fungi and storing them for one day, 200p of the compound of the present invention as an active ingredient (in the form of an aqueous suspension of local emulsion) was added as an active ingredient. ) was sprayed on a turntable using a spray gun*.After spraying, it was stored at a temperature of 25℃ for 10 to 14 days, and the control effect of each was compared with the untreated area. Examined.

The criteria for judging the control effect are the same as in test fllK.

The results are shown in Table 4.

WA4 table! ¥/i/ Finally, examples of formulations in which active ingredients are formed into desired dosage forms are shown as examples.

Example 1 A wettable powder compound: 15 parts, clay clay mixture, 4 parts, bozoxyethylene, 7 parts, nonylphenyl ether, and 5 parts were uniformly mixed to form a wettable powder.

Example 2 Emulsion Compound 120 20 parts Tetrahydrofuran 20 parts Quincea
An emulsion made by uniformly mixing and dissolving 45 parts.

Example 3 Powder Compound 78 4 parts Silica 9 Earthen Clay Mixture of Merck 95s Calcicum stearate A powder prepared by pulverizing the whole powder to 1 m.

Example 4 Granule compound v! J56 3 parts bentonite clay mixture 92 parts Patent applicant
Continuation of page 1 of Nihon Nohyaku Co., Ltd. 249/10 7132-4 C295
/18 6917-4C4011068
214-4C //AOIN 37/18 6526-
4H37/34 6526-4H431
507055-4H A61K 31/40 ADB 31/41 31/415 31/445 31/455 (C07D 401106 11100 233100) (C07D 401106 11100 249100) 0 Inventor Kunika Hiraga Osaka City Area Higashi-ku Shigino Nishi 3-4゜ - 305 0 inventors Tadashi Shibayama - 5-51-8 Yasuokaderamachi, Takatsuki City 0 inventors Ken Ikeda - 1-6-1-302 Higashiizumioka, Toyonaka City 0 inventors Yukio Miyagi 5-6 Hondacho, Kawachinagano City

Claims (1)

[Claims] Represents an atom. ), R1 represents an alkyl group having 1 to 10 carbon atoms, a phenyl group, or a phenoxy group substituted with a halogen atom, R4#'i Mizuki atom, an alkyl group having 1 to 5 carbon atoms; group, allyl group, alkoxycarbonylalkyl group or phenyl group, RmFi alkyl group having 1 to 8 carbon atoms, allyl group,
Cycloalkyl group, ventridine group, different groups, lower alkyl group, lower alkoxy group, halogen atom, nitro group, cyano group, acetyl group, trifluoromethyl group, alkoxycarbonyl 4 The parent is p-methyl represents a phenethyloxy group, t represents an integer from 1 to 5,
) n substituted phenyl group, benzyl group, in α, R
s represents a halogen atom, m represents an integer from 1 to C, and R2 and R3 together with the nitrogen atom represent a substituted benzylkyl group represented by
i Lower alkyl group, hydroxycarbonyl group, alkoxycarbonyl group or benzyl group t [I, n is 1 to 2
represents an integer. ) and the substituted piperidine ring, hexamethyleneimine, is a hydrogen atom or a 710-gen atom. ) A fatty acid amide derivative represented by the piperazine ring ′ represented by ] and salts of 7.