JPH05117255A - Oxadiazole and thiadiazole derivative and their production - Google Patents

Abstract

PURPOSE:To provide a new compound capable of being profitably synthesized and safely used and excellent in the antibacterial activity and in the herbicidal activity. CONSTITUTION:A compound of formula I [X is O, S; R1 is (substituted) phenyl, (substituted) benzyl, (substituted) naphthyl, etc.; R2 is (substituted) phenyl, (substituted) naphthyl, (substituted) pyridyl; R3 is H, lower alkyl]. For example, 3-(2,6-dichlorophenyl)-5-(4-chlorophenylamino)-1,2,4-oxach-lorophenyl) -5-(4- chlorophenylamino)-1,2,4-oxadiazole. The compound of formula I is obtained e.g. by reacting a compound of formula II with a compound of formula III in the presence of an organic base such as triethylamine in a solvent such as methylene chloride.

Description

Detailed Description of the Invention

[0001]

TECHNICAL FIELD The present invention relates to a novel oxadiazole and thiadiazole derivative and a method for producing the same.

[0002]

2. Description of the Related Art In recent years, antibiotics such as penicillin and cephalosporin derivatives have been researched and developed with remarkable speed,
Drugs showing remarkable effects on infections caused by Gram-positive or Gram-negative pathogenic bacteria are being released one after another. on the other hand,
Along with this, intractable deep-seated dermatomycosis and visceral mycosis are increasing, but the indications of currently marketed antifungal agents are limited due to side effects. Therefore, development of an antifungal drug that is harmless to humans and animals and has few side effects is awaited. On the other hand, in the cultivation of agricultural and horticultural crops, many control agents are used against pests and diseases of crops, but their use is limited due to insufficient control efficacy or the emergence of drug-resistant pathogens and pests. However, it is difficult to say that it is a satisfactory control agent, because it causes phytotoxicity or contamination of plants, or is highly toxic to humans and fishes. Therefore, there is a demand for the emergence of a drug that can be used safely with few such drawbacks. Furthermore, many herbicides have come to be used for controlling weeds, which have required a great deal of labor in cultivating agricultural and horticultural crops. However, since it causes phytotoxicity to crops, remains in the environment, and pollutes, it is desired to develop a drug that has a lower dose and is surely effective and can be used safely.

[0003]

SUMMARY OF THE INVENTION An object of the present invention is to provide a novel compound having antibacterial activity and herbicidal activity, which can be synthesized industrially advantageously, has a certain effect, and can be used safely.

[0004]

SUMMARY OF THE INVENTION

[Chemical 11] (In the formula, X represents an oxygen atom or a sulfur atom, R ₁ represents an optionally substituted phenyl group, an optionally substituted benzyl group, an optionally substituted naphthyl group or an optionally substituted naphthylmethyl group. R ₂ represents an optionally substituted phenyl group, an optionally substituted naphthyl group or an optionally substituted pyridyl group, and R ₃ represents a hydrogen atom or a lower alkyl group. Salt and manufacturing method. The substituents on the phenyl group, benzyl group, naphthyl group, naphthylmethyl group or pyridyl group include, for example, C ₁ -C ₆ lower alkyl groups such as methyl group, ethyl group and hexyl group, lower haloalkyl group, lower alkoxy group A lower haloalkoxy group, an aryl group, and a halogen atom, which may be two or more different species.

The method for producing the compound of the present invention is as follows. (1)

[Chemical 12] This reaction is carried out in the presence of organic bases such as triethylamine, pyridine, N, N-dimethylaniline, DBU or inorganic bases such as potassium carbonate, sodium carbonate, sodium hydroxide, halogenated hydrocarbons such as chloroform and methylene chloride, diethyl ether. It is carried out in a solvent such as ethers such as ether and dioxane.

(2)

[Chemical 13] This reaction is carried out in the presence of an organic base such as triethylamine, pyridine, N, N-dimethylaniline, DBU or an inorganic base such as potassium carbonate, sodium carbonate, sodium hydroxide, D
It is carried out in a solvent such as MSO, DMF or acetonitrile.

(3)

[Chemical 14] This reaction is carried out by oxidative ring closure of the compound represented by the general formula [VI] (wherein R ₁ and R ₂ have the same meanings as described above) with bromine, iodine or another oxidizing agent. The compound represented by the general formula [VI] (wherein R ₁ and R ₂ have the same meanings as described above) is

[Chemical 15] Can be manufactured in.

(4)

[Chemical 16] In the formula, R ₃ ′ represents a lower alkyl group and Hal represents a halogen atom. This reaction is carried out in the presence of an inorganic base such as potassium carbonate, sodium carbonate, sodium hydroxide or the like or an organic tertiary amine such as triethylamine or DBU, for example, C
It is carried out by reacting H ₃ I with a halogenated hydrocarbon such as acetonitrile, chloroform or methylene chloride, or a solvent such as DMF.

In any case, the desired product can be obtained by carrying out a usual post-treatment after the reaction. The structure of the compound of the present invention was determined by IR, NMR, MASS and the like.

[0010]

EXAMPLES Next, the compounds of the present invention will be further described with reference to examples. Example 1 3- (2,6-Dichlorophenyl) -5- (4-chlorophenylamino) -1,2,4-oxadiazole (Compound No. 30)

[Chemical 17] 5 g of 2,6-dichlorobenzamidoxime and N- (p-
Chlorophenyl) imidocarbonyl chloride 5.1 g
Is dissolved in 100 ml of chloroform, and 3.7 g of DBU is added with stirring at 0 ° C. After reacting at 0 ° C. for 2 hours, it was further reacted at room temperature for 12 hours. It was poured into ice, extracted with ethyl acetate, dried over magnesium sulfate, and concentrated. Purified by silica gel column chromatography, 3- (2,
2.3 g of crystals of 6-dichlorophenyl) -5- (4-chlorophenylamino) -1,2,4-oxadiazole
Got mp195-196 ° C.

Example 2 3- (2,6-dichlorophenyl) -5-phenylamino-1,2,4-oxadiazole (Compound No. 26)

[Chemical 18] 5 g of 3- (2,6-dichlorophenyl) -5-trichloromethyl-1,2,4-oxadiazole and 1.4 g of aniline were dissolved in 20 ml of DMSO, and DBU was cooled with ice.
Add 2.3 g. After reacting overnight at room temperature, it was poured into ice and extracted with ethyl acetate. The extract was dried over magnesium sulfate, concentrated and purified by silica gel column chromatography to give 3- (2,6-dichlorophenyl) -5-phenylamino-1,2,4-oxadiazole as a crystal 0.4 g.
Got mp. 194-196 ° C

Example 3 3- (2-Methylbenzyl) -5- (4-chlorophenylamino) -1,2,4-thiadiazole (Compound No. 48)

[Chemical 19] 2-Methylbenzylamidine (1 g) and 4-chlorophenylisothiocyanate (1.1 g) were dissolved in DMF (20 ml) and reacted overnight at room temperature. After concentration, water was added, extracted with ether, and recrystallized with a benzene-hexane solvent,
1 g of imidoylthiourea derivative was obtained. 0.5 g of the imidoylthiourea derivative was dissolved in 20 ml of methylene chloride, 0.12 g of pyridine was added under ice cooling, and bromine was added in an amount of 0.
25 g was added dropwise. The mixture was reacted at room temperature for 1.5 hours, poured into water, extracted with ether, and concentrated. Purified by column chromatography, 3- (2-methylbenzyl) -5- (4
0.45 g of crystals of -chlorophenylamino) -1,2,4-thiadiazole were obtained. mp. 133-134 ° C Table 1 shows representative examples of the compound of the present invention including the above-mentioned examples.

[0013]

[Table 101]

[Table 102]

[Table 103]

[0014]

【The invention's effect】

Test Example 1 Antibacterial Test Using a 96-well microplate, the MIC (minimum growth inhibitory concentration μg / ml) was determined by the liquid medium method. D
Compound dissolved in MSO was added to Trychophyton
If mentagrophytes of (ringworm) in Sabouraud glucose medium, Piricularia or
In the case of yzae (rice blast fungus), it was diluted with a potato dextrose medium so that the concentration of DMSO did not exceed 1%. Spore suspension (200,000-500,000 spores / ml) was inoculated, and after 3-7 days, it was measured with a photometer for microplate at 450 n.
The absorbance at m was measured, and the concentration when it became 0.02 or less was taken as the MIC. The results are shown in Table 2.

[0015]

[Table 201]

[Table 202] Test Example 2 Germination Test 1 part by weight of the active compound was dissolved in 100 parts by weight of acetone or dimethylsulfoxide and diluted with sterilized distilled water to obtain a test solution having a predetermined concentration. A circular filter paper (radius 4.0 cm) was placed in a transparent plastic container (bottom radius 3.9 cm × height 4.5 cm), and 9 ml of the test solution was added. Edible Echinochloa ut on filter paper
ilis , Kogomegayatsu Cyperus iria ,
10 to 20 seeds of Lactuca sativa and lettuce, respectively, and covered with a transparent plastic lid.
The plants were grown for 12 days in a growth room with illumination (3,000 lux) at a temperature of 12 ° C. under a 12-hour photoperiod, and the inhibitory damage to the growth of each plant was observed. The results are displayed as follows: 0 = no activity, 1 = 20% growth inhibition, 2 = 40% growth inhibition, 3 = 60% growth inhibition, 4 =
80% growth inhibition, 5 = complete death. The result is the third
Shown in the table.

[0016]

[Table 3]

The compound of the present invention is a compound of Botrytis ci
nerea (green bean fungus), Cercosp
ora beticola ( Mottled beet leaf spot fungus), Mo
nilia fructicola (peach sterilization disease),
Pseudocerocosporella herp
It also has activity against otrichoides (wheat eye-spot disease bacteria) and the like.

─────────────────────────────────────────────────── ─── Continuation of front page (51) Int.Cl. ⁵ Identification number Internal reference number FI Technical indication location C07D 417/12 213 9051-4C (72) Inventor Masae Masae 345 Yanagicho, Takada, Odawara, Kanagawa Japan Soda Co., Ltd. Odawara Research Center

Claims (5)

[Claims] 1. Chemical formula 1 (In the formula, X represents an oxygen atom or a sulfur atom, R ₁ represents an optionally substituted phenyl group, an optionally substituted benzyl group, an optionally substituted naphthyl group or an optionally substituted naphthylmethyl group. R ₂ represents an optionally substituted phenyl group, an optionally substituted naphthyl group or an optionally substituted pyridyl group, and R ₃ represents a hydrogen atom or a lower alkyl group. salt. 2. Chemical formula 2 (In the formula, R ₁ has the same meaning as described above.) (Wherein R ₂ has the same meaning as described above), and a compound represented by the formula: (Wherein R ₁ and R ₂ have the same meanings as described above). 3. Chemical formula 5 (In the formula, R ₁ has the same meaning as described above) and a compound represented by the general formula [V] R ₂ NH ₂ [V] (wherein R ₂ has the same meaning as described above). A compound characterized by reacting a compound (Wherein R ₁ and R ₂ have the same meanings as described above). 4. Chemical formula 7 (Wherein R ₁ and R ₂ have the same meaning as described above) by oxidative ring closure. (Wherein R ₁ and R ₂ have the same meanings as described above). 5. Chemical formula 9 (In the formula, X represents an oxygen atom or a sulfur atom, and R ₁ , R ₂
Has the same meaning as described above. Compounds of the general formula [VII] R ₃ '-Hal (VII) (wherein, R _3' represented by) a lower alkyl group, Hal is a characterized by reacting a compound represented by a halogen atom.) (10) (In the formula, X, R ₁ , R ₂ and R ₃ ′ have the same meanings as described above.)