CA1324608C - Imidazole derivatives, an antibacterial and antifungal agent comprising said derivatives, and a process for the production of said imidazole derivatives - Google Patents

Abstract

ABSTRACT

Imidazole derivatives which were provided as the new compound according to this invention and are re-presented by the formula:

Description

SPECIFICATION
.

NEW IMIDAZOLE DERIVATIVES, AN ANTIBACTERIAL AND ANTI-FUNGAL AGENT COMPRISING SAID DERIV~TIVES, AND A PROCESS
FOR THE PRODUCTION OF SAID IMIDAZOLE DERIVATIVES

Technical Field This invention relates to new imidazole derivatives showing the antibacterial and antigungal activities against such microorganisms pathogenic to plants. This invention also relates to an antibacterial and antigungal agent of the agricultural and horticultural utilities, comprising said new imidazole derivative as the active ingredient.
Further, this invention relates to a procesfi for the production of the new imidazole derivatives which show the antibacterial and antifungal activities against such microorganisms pathogenic to plants.
Background Art Various imidazole derivatives have already been known. ~apanese patent application first publication ~ ~KOKAI) No. 150590/83 discloses N,N'-substituted azole-; 20 carboxamide derivatives represented by the formula:

Rl C~-COO 2 O \~ y ~F~

-` 1 3~4~8 wherein Rl denotes a hydrogen atom, methyl group or ethyl group, R2 denotes a lower alkyl group, X and Y each denote a carbon atom or a nitrogen atom, provided that when X is a nitrogen atom, Y is a nitrogen atom or a carbon atom, and S when X is a carbon atom, Y is a nitrogen atom, as the imida-zole compounds having the antibacterial and antigungal activities against such microorganisms pathogenic to plants.
With these known imidazole derivatives as disclosed in said Japanese patent application first publication (KOKAI) No. 150590/83, they can be expected to show their effects of controlling the plant diseases such as cucumber powdery mildew, cucumber scab and the like, when they are applied to the infested plants as a solution containing a high concentration of said imidazole derivatives in the range of 250 to 500 ppm. as a solution containing a lower concentration of said imidazole derivatives in the range of 100 to 10 ppm. to the infested plants, they can hardly exhibit their effects of controlling the plant diseases.
Further, these known imidazole derivatives have substantially no effect or disinfecting the seeds, so that they cannot be utilized as the agent for disinfecting the seeds for the purpose of controlling "bakanae" disease and brown spot of rice plants.
An object of this invention is to provide new imidazole derivatives wh~ch can be used as a substitute ~':

for the known imidazole derivatives, and which are appli-cable as more useful antibacterial and antigungal agent of agricultural ~nd horticultural utilities and, parti-cularly also as the agent for disinfecting the seeds to control "Bakanae" disease and brown spot of rice plants.
Another objects of this invention is to provide an anti-bacterial and antifungal agents of agricultural and horticultural utilities, comprising said new imidazole derivatives as the active ingredient. Further object of this invention is to provide a process for the production of said imidazole derivatives.
We, the present inventors, have synthetized a lot of new imidazole derivatives which are similar to the known imidazole derivatives mentioned above, in respect of their basic chemical structure but which are bearing such substituent(s) different from the substituent(s) on said known imidazole derivatives. ~e have extensively studied these new compounds for their biological activities. As a result, we have found that new imidazole derivatives represented by~the general formula (I) R4 ~ IRl CH-COOR3 ~ X ~ \ ~ N (I) i\~

- -` 1 324608 wherein Rl denotes a hydrogen atom or a lower alkyl group, R2 denotes a lower alkyl group, R3 denotes an alkenyl group, a cycloalkyl group, an alkoxy alkyl group or a higher alkyl group, R4 denotes a hydrogen atom or a lower alkyl group, and X denotes an oxygen atom or a sulfur atom, have excellent antibacterial and antifungal activities and that these compounds are more excellent and effective as the antibacterial and antifungal agent of the agri-cultural and horticultural utilities.
Disclosure of The Invention .
According to the first aspect of this invention, there is provided an imidazole derivative represented by the general formula (I) lR2 4 ~ IRl / CH-COOR3 ~ X ~ \ f==N (I) o \l wherein Rl denotes a hydrogen atom or a lower alkyl group, R2 denotes a lower alkyl group, R3 denotes an alkenyl group, a cycloalkyl group, an alkoxyalkyl group or a higher alkyl group, R4 denotes a hydrogen atom or a lower alkyl group, and X denotes an oxygen atom or a sulfur atom.

s For the compound of the formula (I) above where Rl, R2 and R4 each denote a lower alkyl group, the lower alkyl group may be a lower alkyl group containing 1 to 6 carbon atoms, such as methyl group, ethyl group, propyl S group, isopropyl group, butyl group, isobutyl group, secondary butyl group, tertiary butyl group, pentyl group, hexyl group, isohexyl group and the like. When R3 is a lower alkenyl group, this lower alkenyl group may be an alkenyl group containing 2 to 10 carbon atoms, such as vinyl group, allyl group, l-propenyl group, 2-methyl-2-propenyl group, l-methyl-2-propenyl group, 2-butenyl group, 3-butenyl group, 2-pentenyl group, 2,4-hexadienyl group, hexenyl group and the like. The cycloalkyl group for R3 may be a cycloalkyl group containing 3 to 6 carbon atoms, and it may preferably be a cyclopentyl group or cyclo-hexyl group. When R3 is an alkoxyalkyl group, it may be a lower alkoxy-lower alkyl group containing 2 to 6 carbon atoms. Preferred examples of the alkoxyalkyl groups for R3 include methoxymethyl group, ethoxymethyl group, pro-poxymethyl group, methoxyethyl group, ethoxyethyl g~oupand propoxyethyl group.
When R3 denotes a higher alkyl group, it may be an alkyl group containing 10 to 20 carbon atoms. Examples of such higher alkyl group may be decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, heptadecyl group, octadecyl group, nonadecyl group and cicocyl group.
According to the second aspect of this invention, there is provided an antibacterial and antifungal agent of agricultural and horticultural utilities, comprising as the active ingredient an imidazole derivative re-presented by the formula (I) 4 ~ Rll / CH-COOR3 X ~ CH-N \ ~ N (I) C-N
O ~
wherein Rl denotes a hydrogen atom or a lower alkyl group, R2 denotes a lower alkyl group, R3 denotes an alkenyl group, a cycloalkyl grop, an alkoxyalkyl group or a higher alkyl group, R4 denotes a hydrogen atom or a lower alkyl group, and X denotes an oxygen atom ox a sulfur group.

lS The compounds of the above-mentioned general formula (I) exhibit the effects for controlling the infesting microorganisms such as those of rice blast, rice brown spot, rice seath blight, tomato late blight, cucumber powdery mildew, cucumber gray mold, barley powdery mildew, kidney bean stem rot, wheat brownrust and the like when they are applied to the infected plants. Furthermore, these , . :

compounds of the formula (I) exhibit the effects for sterili~ing the seeds to prevent the plant diseases such as rice "bakanae" disease and rice brown spot.
Pathogenic microorganisms in the soil, such as those causing the damping-off disease of beet can also be controlled by treating the soil with the compounds of the formula (I) according to this invention. The effects of the compounds of this invention for controlling the plant diseases are not be limited to the effects of con-trolling the particular examples of the diseases specifiedabove, and various diseases of rice, barley and wheat, vegetables, fruit trees and the like can effectively be controlled by applying the compounds of this invention onto the foliage of the plants, by disinfecting-the seeds or by treating the soil with the compound.
The antimicrobial agent of the agricultural and horicultural utilities according to the second aspect of this invention may be formulated into various types of pre-parations such as dust, wettable powder, emulsifiable concentrate granules, fine granules and other conventional formulation forms. In preparing these formulation in the different forms, the carrier to be used may be any of the liquid or solid carriers and not be limited to specific ones.
For example, solid carriers may be various grades of clays, kaoline, clay, diatomaceous earth, talc, silica 1 32460~

and the like. Liquid carriers may be a liquid which can be a solvent for dissolving the imidazole derivative com-pounds of the formula (I), or a liquid which itself can-not be a solvent for dissolution of said imidazole compounds but can disperse or dissolve therein said imidazole com-pounds with aid of an adjuvant. For example, benzene, xylene, toluene, kerosin, alcohols, ketones, dimethyl-sulfoxide, dimethylformamide and the like are available for this purpose. Appropriate surface-active agents and other adjuvants such as spreading agent and sticking agent may be mixed with said organic liquids so that the mixture may be formulated into aqueous solutions or emulsions.
The antimicrobial composition containing the imidazole compound of the general formula tI) may further contain other additives such as other antimicrobial agents, insecticides, herbicides and plant-growth-regulating agents for the reduction of labor power and for ensur ng the controlling effects of the imidazole compounds.
According to the third aspect of this invention, there is provided a process for the production of an imidazole derivative represented by the formula (I):

R ~ 1l / CH-COOR3 (I) C-N

g wherein Rl is a hydrogen atom or a lower alkyl group, R2 is a lower alkyl group, R3 is an alkenyl group, a cyclo-alkyl group, an alkoxyalkyl group or a higher alkyl group, R4 is a hydrogen atom or a lower alkyl group, and X is S an oxygen atom or a sulfur atom, which comprises reacting a carbamoyl chloride compound of the~formula (II):

R4 ~ ll / CH-COOR3 CH-N \ (II) O
wherein R1, R2, R3, R4 and X are as defined above, with imidazole of the formula (III):

~\
¦ NH (III) N ~
in an organic solvent which is unreactive in the reaction involved.
In the process according to the third aspect of this invention, the reaction of the carbamoyl chloride compound of the formula ~II) with imidazole of the formula (III) may preferably be conducted in the presence of a base such as carbonate, a hydrogen carbonate or a hydro-xide of an alkali metal, or a trialkylamine and pyridine.
Preferred examples of such bases include basic com-pounds such as potassium carbonate, sodium hydro~en carbonate, sodium hydroxide, triethylamine and pyridine.Examples of the organic solvent to be used as the reaction medium may be an unreactive solvent such as acetone, methylethylketone, acetonitrile, dimethyl-formamide, dimethylsulfoxide or dioxane. The amount of imidazole used for this reaction may preferably be in a range of 1.0 to 5.0 mol. per 1 mol. of the carbamoyl chloride compound of the general formula (II), and the base may preferably be used in an amount of 0.5 to 5.0 mol. per 1 mol. of the carbamoyl chloride compound of the general formula (II). This reaction is performed at a temperature of 20 to 150,C, preferably of 50 to 120C.
The starting carbamoyl chloride compound of the general formula (II) above may easily be synthetized by reacting a secondary amine represented by the formula (IV):
R4 ~ ll R2 (IV) wherein Rl, R2, R3, R4 and X are as defined above, with phosgene ~COC12) or with trichloromethyl chloroformate of the formula ~V):

o C13C-OCCl ~V) in an organic solvent which is unreactive in the reaction.
The reaction for this synthesis is depicted by the following ~ 324608 reaction equation (1) or (2), X3-cH-NHcHcOOR3 + COCl2 (IV) - (phosgene) ~ 13 N / 3 I (II) (2) ~ CH-NHCHCOOR3 + ~ C13C-OCCl >
(IV) (V) R4 ~ 1l / CHCOOR3 (II) Best Mode of working the Invention Representative examples of the imidazole derivative compounds of the general formula (I) according to the first aspect of this invention are listed in Table 1 below:

-` 1 3246~8 Table 1 4 ~ ~ 1l / CH-COOR3 CH-N \ ~ N ~I) C-N

4 ~ Physical data Cbmpound ~ ~ R (Refractive index or No X 1 R2 R3 Melting point) 1 ~ H -C2H5 C12H5 nD 1.5193 -CHCH=CH2 2 ~ " " 2 H2 C2H5 nD2 1.5062 3 " ~ -C3H7-n -(CH2)3CH=CH2 nDl 1.5112 4 " " " -CHCH=CH2 nDl 1.5157 " " -C2H5 2)2 H2 nD 1.5180 6 ~ ~C3H7~n ll nD 1~5018 2H5 -(CH2)3CH-CH2 nD 1.5163 8 ll ~ " CIH3 nD 1.5198 -CHCH_CH2 9 " " -C12H25-n nD 1.4959 " " " -C14H29-n nD 1.4942 Table 1 (cont'd) 4 ~ Physical data Cbmpound c ~
No ~ X~ R R R ~Refract1ve index or . 1 2 3 _ Melting point) Il ~ H -CH3 -CH2CH=CH2 nD 1.5242 12 " -C3H7-i ~ n23 1.5149 13 -" " 3 7 2 H CHCH3 nD 1.5174 14 ~ " 2H5 nl9 1.5217 -C4Hg-n -CH2CH=CH2 nD 1.5123 16 ~ " -C3H7~n ~ nD 1.5147 17 " " -C3H7-n -CH2CH-CH nD9 1.5191 18 ' " -C2H5 ~ nD 1.5187 19 " -C2H5 -CH2CH=CH2 m.p. 69-71C

~ ll -c3H7-n -(CH2)2cH CH2 nD 1.5423 21CH3 ~ -C2H5 -CH2CH~CH2 nD3 1.5436 22 ~ " -C2H5 -C14H29-n nl5 1.5100 23 ll -CH3 " -CH2CH=CH2 n23 1.5444 24 ll H -C3H7-n -(CH2)3CH CH2 PD 1.5353 , ~
.

- .-.

- 1 32~60~

Table 1 (cont ' d ) 4 ~3_ Physical da'ca (X)mpound ~ R R R ~Re:Exactive in~ex or No. X 1 2 3 Melting point ) 1 . .. ___ __ ~ S "~ -C2H5 -CH2CH=CH2 nD 1.5454 26 ~ " -C3H7-n fH3 nDl 1.5420 -CH-CH=CH2 27 " " -C2H5 2 2 2 nD 1.5429 28 -CH2CH=CH-CH3 nD 1.5401 29 ~ ( 2)3 H CH2 nD7 1.5397 " " " fH3 nDl 1.5474 -CH-CH=CH2 31 ~ C3H7-n -CH2CH=CHCH3 nDl 1.5420 32 " " -C2H5 -C12H25-n nD 1.5106 33 " " -CH3 -CH2CH=CH2 ~ 1.5482 34 " " -C H -n ~ nD 1.5358 " " -C3H7-n CH2CH=CH2 nD7 1.5252 36 " C2H5 ~ n~ 1. 5399 37 " " " -CH2CH=CH2 nD 1.5476 _ '' "

.

The Compound Number shown in Table 1 above is referred to in the Examples given hereinafter.
The process for the production of the compounds of the formula (I) according to this invention is now illust-rated with reference to the Examples below.
Example 1 Preparation of N-l-(l-cyclohexyloxycarbonylbutyl)-N-(l-imidazolylcarbonyl)-furfurylamine (Compound No. 16).
N-l-(l-cyclohexyloxycarbonylbutyl)-N-furfuryl-carbamoyl chloride (4 g, 0.012 mol.) was dissolved in dimethylsulfoxide (S0 ml), to which were added imidazole (2.5 g, 0.037 mol) and triethylamine (1.5 g, 0.015 mol).
The mixture obtained was stirred for 30 minutes at 100C
under heating. After completion of the reaction, the reaction mixture was admixed with water and extracted with toluene. The organic solvent layer separated was concentrated and purified by column-chromatography to afford the titled compound as a yellowish orange colored liquid (2.8 g).
Example 2 Preparation of N-l-(l-allyloxycarbonylpropyl)-N-(l-imidazolylcarbonyl)-furfurylamine (Compound No. L9).
N-l-(l-allyloxyc~rbonylpropyl)-N-furfuryl-carbamoyl chloride (10 g, 0.033 mol) was dissolved in N,N-dimethylformamide (100 ml), to which were added imidazole (10 g, 0.15 mol) and potassium carbonate ~5g, 0.036 mol).
The mixture was stirred for 1 hour at 70C under heating.
After completion of the reaction, the reaction mixture was admixed with water and extracted with toluene. The organic solvent layer separated was concentrated and the resultant residue was recrystallized from a solvent mixture of toluene-n-hexane to afford the titled compound as colorless crystals (9.2 g).
Example 3 .. . _ .
Preparation of N-l-(l-allyloxycarbonylbutyl)-N-(l-imidazolylcarbonyl)-2-thienylmethylamine (Compound No. 35).
N-l-(l-allyloxycarbonylbutyl)-N-2-thienylmethyl-carbamoyl chloride ~3.2 g, 0.010 mol) was dissolved in acetonitrile (50 ml), to which were added imidazole ~O.g g, 0.013 mol) and pyridine (3.5 g, 0.044 mol). The mixture was heated for 2 hours at ~0C. After completion of the reaction, the reaction mixture was processed in a same manner as in the Example 1, to obtain the titled compound as a yellowish orange colored liquid (1.5 g).
Some Examples are now given below to illustrate the uses of the imidazole compounds of the general formula (I) as the antibacterial, antifungal agent of the agricultural and horticultural utilities.
Example 4 (Dust) 2 Parts of Compound No. 17 identified hereinbefore and 98 parts of clay were mixed and milled uniformly to yield a dust preparation containing 2% of the active ingredient.
Example 5 (Wettable powder) 30 Parts of Compound No. ll identified hereinbefore, 3 parts of calcium alkylbenzenesulfonates, 5 parts of polyoxyethylenenonylphenylether and 62 parts of China clay were mixed and milled uniformly to obtain a finely divided, homogeneous wettable powder containing 30% of the active ingredient. For practical use, the wettable powder thus prepared may be diluted with water to a volume of 600 to lO00 folds larger than the original volume, for ' being sprayed onto the plants.
Example 6 (Emulsion) .
30 Parts of Compound No. lS identified hereinbefore, 40 parts of methylethylketone and 30 parts of polyoxy-', 20 ethylenenonylphenylether were mixed to give a solution, so that an emulsifiable concentrate containing 30X of the active ingredient was obtained. When used as the anti-microbial agent, the emulsifiable concentrate thus prepared may be diluted with water to a volume of 600 to lO00 folds larger than the original volume, for being sprayed onto -`` 1 3246a~

the plants.
Example 7 (Granules) A mixture of 5 parts of Compound No. 5 listed hereinbefore, 1.5 parts of lauryl sulfate, 1.5 parts of calcium ligninesulfonate, 25 parts of bentonite and 67 parts of white clay was further admixed with 15 parts of water. The resultant mixture was kneaded in a kneader.
The mixture was then granulated and dried in a fluidizing, drying apparatus to obtain granules containing 5% of the active ingredient.
The following Test Examples illustrate the con-trolling effects of the imidazole derivative compounds of the formula (I) when applied as the antimicrobial agent of the agricultural and horticultural utilities. In the comparative tests of the following Test Examples, there were used as the Comparative compound some compounds which are disclosed in the Japanese patent application first publication (KOKAI) No. 150590/83 and which have respective-ly the following chemical formulas:
Comparative Compound No. 1 L ~ CHCOOC4Hg-n C - N ~

~" 1 32~8 Comparative Compound No. 2 ~o ~ CH2-N ~ ~ N
C - N
~- 11 ~ , O
Comparative Compound No. 3 fH3 o ~ 2 \ ~ N
Il \~

O
Test Example 1 Tests for controlling rice blast Seedlings of paddy rice plant (variety: Asahi) ~: as grown to the third leaf stage, which had been cultured in non-irrigated soil in unglazed pots (9 cm in diameter) in a green house, were sprayed with test solutions. Each of these test solutions had been prepared by diluting with water to the predetermined concentration of the acti~e ingredient such a wettable powder which was formulated according to the Example 5 and which contained a test compound indicated in Table 2 as the active ingredient.
One day after the spraying of the test solution, a suspension of spores of the pathogenic microorganism of rice blast (Pyricularia oryzae) was sprayed over the paddy rice seadlings for inoculation. After the inoculation, the seedlings in the pots wére placed and maintained overnight under the conditions of a humid chamber (where a humidity of 95 to 100X and a temperature of 24 to 25C prevailed). Five days after the inoculation, the number of the lesions per leaf on the third leaf of the rice plant was counted, and the rate (%) of the con-trolling effects of the tested compound was evaluatedaccording to the following equation. Degree of phyto-toxicity to the rice plant was estimated according to the following index. The test results are shown in Table 2.

Rate (X) of the controlling effects =

Number of the lesions in the treated plot (1 Number of the ~esions in the untreated plot) x 100 Index for phytotoxicity:-5: Very severe 4: Severe 3: Moderate 2: Slight 1: Negligible 0: None . ~ . , Table 2 Concentration of active ingredient Rate of Test compound in the sprayed controlling Degree of No. solution (ppm) effect (%) phytotoxicity ..
12 200 90 0.
13 200 lO0 0 200 lO0 0 .
Comparative tests Comparative 200 o o compound No. 1 compound No. 2 200 50 0 Comparative compound No. 4 480 72 0 (IBP) _ _ . . . _ Untreated - 0 (25) .
Note 1: The Comparative compound No. 4 (IBP) is a com-mercially available fungicidal agent containing S-benzyl O,O-diisopropyl phosphorothioate.

Note 2: The figure given in the parenthesis shows an averaged number of the lesions per leaf in the untreated plot.

Test Example 2 Tests for controlling rice brown spot Seadlings of paddy rice plant (variety: Asahi) as grown to the fourth true leaf stage, which had been .. , . :

, , .; .

~` ~ 324608 .

cultured in the non-irrigated soil in unglazed pots (9 cm in diameter) in a green house, were sprayed with the test solutions which had been diluted with water to a pre-determined concentration of the active ingredient. One day after the spraying, a suspension of conidiospores of the pathogenic microrganisms of rice brown spot ~Cochlio-bolus miyabeanus) was sprayed over the seedlings for inoculation. Five days after the inoculation, the number of the lesions per leaf on the fourth true leaf of the rice plant was counted, and the rate ~%) of the controlling effects of the tested compound was evaluated according to the following equation. Degree of phytotoxicity to the rice plant was estimated in the same manner as the Example , 1~ The test results are shown in Table 3 below.
lS Rate (%) of the controlling effects =

(1 Number of the lesions in the treated plot Number of the lesions in the untreated plot) x 100 -` 1 3246~8 Table 3 Concentration of active ingredient Rate of Test Compound in the sprayed controlling Degree of No. solution (ppm) effects (%) phytotoxicity 1 200 . 100 0 2~0 100 0 .
Cbmp3ratlve tests compound No. 1 200 0 compound No. 2 200 0 compound No. S 200 98 0 (I~rodione) -Untreated - 0 (53) .......

^` 1 324608 Note 1: The Comparative compound No. 5 (Iprodione) is a commercially available fungicidal agent con-taining 3-(3,5-dichlorophenyl)-N-isopropyl-2,4-dioxoimidazolidine-l-carboxamide.
Note 2: The figure given in the parenthesis shows an averaged number of the lesions per leaf in the untreated plot.
Test Example 3 Tests for controlling barley powdery mildow Seedlings of barley (variety: Azuma Golden) as grown to the first leaf stage, which had been cultured in the soil in unglazed pots (9cm in diameter) in a green house, were sprayed with test solutions at a rate of 10 ml per 2 pots. Each of the test solutions sprayed had been prepared by diluting the wettable powder as prepared according to the Example 5, with water to the predetermined concentration of the active ingredient.
The next day after the treatment, the inoculation was made by lightly scattering the spores of barley powdery mildew (Erysiphe graminis Sp. hordei) which had pre-viously been developed on the leaves of barley, onto the treated leaves of barley plants. Seven days after the inoculation, the number of the fungal colonies of ; barley powdery mildew per leaf was assessed, and the rate (%) of the controlling effects of the tested compound was evaluated according to the following equation.

Degree of phytotoxicity to barley was estimated according to the index similar to the Test Example 1.
Rate (%) of the controlling effects e er of the colonies per leaf in the treated plot (1 N~er of the colonies per leaf in the untreated plot) x 100 The results are shown in Table 4 below.

~, , ,~

....

. . .

~ ' ' -`` 1 324608 Table 4 Concentration of active ingredient Rate of Test Compound in the sprayed controlling Degree of No _ solution (ppm)effect (%) phytotoxicity 11 10~ 100 O

'28 100 96 0 ... .

- 1 3246~8 Table 4 ~cont~d) Concentration of active ingredient Rate of Test Compound in the sprayed controlling Degree of No. solution (ppm) effect (%) phytotoxicity ~parative tests compound No. 1 100 0 Comparative 100 o o - Comparative compound No. 6 100 85 0 (Quinomethionate) ,: _ ._ , . _ _ : Untreated - O
` (100) Note 1: The Comparative compound No. 6 (Quinomethionate) is commercially available fungicidal agent ; containing 6-methyl-`1,3-dithiolo[4,5-6]quinoxaline-2-one.
Note 2: The figure given in the parenthesis shows an , average number of the fungal colonies per leaf in the untreated plot.

., . .
.

Test Example 4 Tests for controlling rice sheath blight Seedlings of rice plant as grown to the sixth leaf stage, which had been cultured in the soil in unglazed pots (9 cm in diameter), were sprayed with the test solutions at a rate of 40 ml per 3 pots. Each of the test solutions contained the active ingredient at a predetermined concentration. The seedlings so treated were allowed to stand in a glass greeen house. One day after the spraying of the test solution, the inoculation - was made by placing adhesively a piece of agar disc containing the mycelium which had been punched out by a cork borer of 10 mm diameter from the edge of mycerial colony of rice sheath blight (Rhizoctonia solani) as cultured or potate sucrose agar medium for 48 hours at 27C, on the bottom of the leaf sheath of the rice plant.
The rice plants so treated were then kept in a humid chamber overnight, Development of the disease was estimated 6 days after the inoculation, by measuring the length of the lesion of the rice sheath blight about each stem of the rice plant, and the rate (%) of the controlling effects of the tested compound was evaluated by comparing the length of the lesion in the treated plot with that in the untreated plot. Degree of phytotoxicity was estimated in the same manner as in the Test Example 1.
Rate (%) of the controlling effects -length of the lesion in the treated plot 1 length of the lesion in the untreated ~lot~ x 100 The test results are shown in Table 5.
Table 5 ~ Concentration of - active ingredient Rate of Test compound in the sprayedcontrolling Degree of No. solution (pp~)effect ~X) phytoto~icity , Comparative tests Comparative compound No. 1 2 0 Comparative compound No. 7 30 88 0 (Validamycin A) , Untreated - 0 - (17) -- .
I ~ .
Note 1: The figure given in the parenthesis shows the length (cm) of`the lesion in the untreated plot.

~;

' .
`

;
Test Example 5 Tests for controlling cucumber gray mold Cucumber plants (Variety; Sagami Hanjiro) as grown to the first true leaf stage, which had been cultured in the soil in unglazed pots (9 cm in diameter) in a green house, were sprayed with the test solutions containing the test compounds as the active ingredient, at a rate of 10 ml per pot. Each of the test solutions was containing the active ingredient at a predetermined concentration and had been prepared by diluting with water a wettable powder which was formulated according to the Example 5 and containing as the active ingredient the test compound indicated in Table 6 below. One day after the spraying of the test solution, inoculation of the pathogenic fungi was performed by placing on the center of the :`
~` each leaflet of the first true leaf stage such a piece of agar disc containing the mycelium which had been pre-pared by punching out, with a cork borer of S mm diameter, !:
from the edge of the mycerial colony of cucumber gray mold ~Botorytis cinera) as incubated for 2 days at 20C on the potate decoction agar medium. The cucumber plants thus treated were kept in a humid chamber for 3 days at 20C to promote the development of the cucumber gray mold fungi.

Three days after the inoculation, length of the lessions of cucumber gray mold was measured with vernier caliper, .

and the rate (%) of the controlling effects of the test compound was evaluated according to the equation given below. Degree of the phytotoxicity to cucumber plant was estimated according to the same index as in the Test Example 1.
Reate (%) of the controlling effects =

length of lesions of cucum~er gray mold in the treated plot (1 length of lesions of cucumber gray ) x 100 mold in the untreated plot The tests-were conducted in two replicates for a . particular concentration of the test compound, and the averaged value of the rates of the controlling effects was calculated.
The test results are shown in Table 6.

Table 6 Concentration of active ingredient Rate of the Test compound in the sprayed controlling Degree of No. solution (ppm) effects (%) phytotoxicity 29 200 95 o . _ .
Comparative tests Comparative 200 0 compound No. 1 Cbmparative 200 0 0 Comparative compound No. 8 200 98 0 (Procymidone) Untreated - o (34) . . . _ Note 1: The Comparative compound No. 8 (Procymidone) is a commercially available fungicidal agent containing N-(3,5-dichlorophenyl)-1,2-dimethyl-cyclopropane-1,2-dicarboximide.
Note 2: The figure given in the parenthesis shows the length (mm) of the lesions in the untreated plots.

1 32460~

Test Example 6 Tests for disinfection of rice seeds infected with rice bakanae disease The rice seeds infected with the Bakanae disease (Fusarium moniliforme) were obtained rom the rice plants (Variety: ~inki No. 33) which has been inoculated by spraying a concentrated suspension of spores of Fusarium moniliforme on the plants at the flowering season. The so infected rice seeds were employed for the tests. Dis-infection of the infected rice seeds was carried out as follows; Wettable powders which were formulated according to the Example 5 and each containing the test compound were diluted with water to the predetermined concentration of the active ingredient, to prepare the test solutions. The lS infested rice seeds were immersed in the test solution at a ratio of the rice seeds to the test solution of 1:1 ~by volume/volume) for 24 hours at 20C for the disinfection.
After the disinfection, the rice seeds were immersed in a water bath for 3 days at 20C for absorption of water and then for 24 hours at 30C for promotion of the germination.
The fully swollen rice seeds were sowed and culti-vated in a nursery box containing soil granules of a trade mark "Kumiai" (as produced by Kureha Chemical Co.,Ltd.) accord-ing to a standard method of nursering the seedlings in ~`

.. , ., , . .~

~ ~ 3246~8 box, followed by cultivation of the rice seedlings in a glass greenhouse. 25 Days after the sowing of the seeds (at the fourth leaf stage), all the seedlings in the treated plots were pulled out from the nursery box.
The assessment of the outbreak of the Bakanae disease was performed in such way that the number of the disease-incidence seedlings was calculated and the percentages of the disease-incidence seedlings based on the whole seed-lings was determined, whereby the rate (%) of the control-ling effects of the test compound was evaluated. Degreeof the phytotoxicity to rice plants was also estimated according to the same standards as that in the Test Example 1.
The tests were performed in three replicates for a particular concentration of the test compound, and the averaged value for the percentages of the disinfected seeds was calculated.
The test result are shown in Table 7 below.

Pçrcentage of the disease-incidence seedlings ~

N~r of the disease;incidenceseedlings 100 Nu of all the seed mgs unde~ F~~~ x Percentage of the sterilized seeds =
percentage of the disease-incidence ~1 seedlings in the treated plot percentage of the disease-incidence ) x 100 seedlings in the untreated plot Table 7 Concentration of active ingredient Percentages of , Test compound in the test the disinfected D~r~e of No. solution (pp~) seeds phytotoxicity . 3 1000 100 0 ~: 7 1000 100 0 . ~ 19 1000 100 0 : 20 1000 100 0 . 25 1000 96 0 29 1000 97 o . ,31 1000 100 0 . .
:- Comparative tests - Comparative 1000 60 :; Compa*ative compound No. 3 1000 0 0 Comparative : compound No. 9 1000 95 0 . ~enomyl) .
Untreated - 0 (57.3) _ ~ .

Note 1: The comparative compound No. 9 (Benomyl) is a commercially available fungicidal agent con-taining l-(n-butylcarbamoyl)-2-benzimidazole-carbamic acid methyl ester.
Note 2: The figure given in the parenthesis shows the percentage of the disease-incidence seedlings in the untreated plots.
Test Example 7 Tests for disinfection of rice seeds infected - with rice brown spot.
The rice seeds as naturally infected with the pathogenic fungi of rice brown spot (Cochliobolus miyabeanns) were obtained from the rice plants in paddy fields where the disease of rice brown spot were frequent-ly occurring, and these infected seeds w~re used for the tests. The method of disinfecting the rice seeds and the other test procedures were same as those in the Test Example 6. The assessment of the out-break of the disease was made 20 days after the sowing of the seeds. The number of the seedlings which had been infested by the rice brown spot was counted, and the percentage of the disinfected seeds was evaluated in the same manner as in the prece-eding tests for the disinfection of the seeds infected with the rice bakanae disease.
Degree of the phytotoxicity to rice plants was estimated according to the same standards as in the Test Example 4.

- ~ . . .. .

The tests were made in three replicates for each test plot, and the averaged value of the evaluated per-centages of the disinfected seeds was calculated. The test results are shown in Table 8.

Table 8 Concentration of ~ active ingredient Percentage of Test compound in the test thedisinfected Degree of No. solution (ppm) seeds phytotoxicity ., lS 1000 97 0 : 19 1000 100 0 37 1000 99 o Cont'd...

, -` 1 324608 Table 8 (cont'd) Concentration of . active ingredient Percentages of Test compound in the test the disinfected Degree of No.solution (ppm) seeds phytotoxicity Comparative tests Comparative1000 0 0 compound No. 2 Comparative 1000 53 0 compound No. 3 Comparative compound No. 5 1000 95 0 (Iprodione) _ . ... . _ . _ _ Untreated -(45) . _ _ _ . . . _ Note 1: The Comparative compound No. 5 (Iprodione) is the same compound as that in the Test Example 2.
Note 2: The figure given in the parenthesis shows the percentage of the disease- incidennce seedlings in the untreated plots.

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.

.. . .

~` 1 32460B

Test Example 9 Tests for controlling damping off disease of beet A soil containing a predetermined concentration of the active ingredient was prepared by mixing thoroughly a soil (100 g) infested with the beet damping off disease ~Rhizoctonia solani), with a dust formulation as prepared according to the Example 4. The soil thus prepared was charged into pots made of a plastic material. Seeds of beet (Variety; Sorolave) were sowed at a rate of 10 grains of the seeds per pot. The pots containing the seeds in the soil were kept at 24C. 10 Days after the sowing of the seeds, the number of the damping-off killed seedlings of beet was counted. Rate (%) of the controlling effects of the test compound was evaluated according to the following equation:

Rate (%) of the controlling effects =
percentage of the damping-off-killed seedlinqs in the treated ~lot (1 percentage of~the damping-off-kiIled ) x 100 seedlings in the untreated plot The tests were made in three replicates for each test plot. From the averaged value of the percentages of the damping-off-killed seedlings in the three pots was calculated the rate of the controlling effects of the test compound. Degree of the phototoxicity to beet :
. . . -; .

was estimated according to the same standards as in the Test Example 1. The test results are shown in Table 9.

Table 9 Concentration of active ingredient Rate of the Test compound in the soil controlling Degree of No. (ppm) effects (%) phytotoxicity ,: 5 50 100 0 ' 6 50 100 0 , 7 50 100 0 . 9 . 50 100 0 , 10 50 100 0 ,, i 12 50 100 0 ,; 13 50 100 0 , .
'; 17 50 100 0 ~- 20 50 100 0 ' 22 50 100 0 ~`` 23 50 100 0 '~ 24 50 100 0 2~ 50 100 0 '~ 27 50 100 0 ,~ 28 50 100 0 :
, Cont'd ;

.

' 1 3246~8 Table 9 (cont'd) Concentration of active ingredient Rate of the Test compound in the soil controlling Degree of No. (ppm) effects (%) phytotoxicity ; 32 SO 100 0 Comparative tests : - _ Comparative 50 compound No. 1 75 Comparative compound No. 2 50 50 Comparative compound No. 10 50 85 0 (PCNB) Untreated - O
(70) .
Note 1: The Comparative compound No. 10 ~PCNB) is a commercially available fungicidal agent - containing pentachloronitrobenzene.
Note 2: The figure given in the parenthesis shows the percentage of the damping-off-killed seedlings in the untreated plots.
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1 ~24608 Industrial Utility of the Invention As described hereinbefore, the new imidazole derivatives according to this invention are useful as the antibacterial and antigungal agent for use in the agriculture and horticulture, and they are suitable for control of the plant diseases.

Claims (4)

1. An imidazole derivative having the formula (I) in which R1 denotes a hydrogen atom or a (C1 - C6) alkyl group, R2 denotes a (C1 - C6) alkyl group, R3 denotes a (C2 - C10) alkenyl group, a (C3 - C6) cycloalkyl group or a (C2 - C6) alkoxyalkyl group, R4 denotes a hydrogen atom or a (C1 - C6) alkyl group, and X denotes an oxygen atom or a sulphur atom.

2. An imidazole derivative as claimed in claim 1 wherein R1 denotes a hydrogen atom, R2 denotes methyl group, ethyl group or a propyl group, R3 denotes allyl group, 1-methyl-2-propenyl group, 2-butenyl group, 3-butenyl group or 4-pentenyl group, R4 denotes a hydrogen atom, and X
denotes an oxygen atom.

3. An antibacterial and antifungal agent for agricultural and horticultural use comprising the imidazole derivatives of claim 1 or claim 2, as the active ingredient, and an inert solid or liquid carrier.

4. A process for the preparation of an imidazole derivative represented by the formula (I) (I) wherein R1, R2, R3, R4 and X are as defined in claim 1, comprising reacting a carbamoyl chloride compound represented by the formula (II) (II) wherein R1, R2, R3, R4 and X are as defined in claim 1, with an imidazole of the formula (III) (III) in a non-reactive organic solvent.