KR960010347B1 - (substituted phenyl)-1h-1.2.4-triazol-1-ylalkenol ether derivatives and process for their preparation - Google Patents

Abstract

The new substituted phenyl-1H-1,2,4-triazol-1-yl alkenol derivatives are 2-(2',4'-dichlorophenyl)-5-(pyrane-2'-yl)oxy-1-triazolyl-2-pen-3-thinol; 2-(2',4'-dichlorophenyl)-5-phenoxy-1-triazolyl-2-pen-3-thinol; 5-(4'-chlorophenyl)oxy-2-(2',4'-dichlorophenyl)-1-triazolyl-2-pen-3-thinol; 2-(2',4'-dichlorophenyl)-5-(2',2'--dimethylprophyl)oxy-1-triazolyl-2-pen-3-thinol; 5-allyloxy-2-(2',4'-dichlorophenyl)-1-triazolyl-2-pen-3-thinol; 2-(2',4'-dichlorophenyl)-5-methoxy-1-triazolyl-2-pen-3-thinol; 5-benzyloxy-2-(2',4'-dichlorophenyl)-1-triazolyl-2-pen-3-thinol; 5-allyoxy-2-(2',4'-dichlorophenyl)-1-triazolyl-2-trans-pen-3-thinol; 2-(2',4'-dichlorophenyl)-5-methoxy-1-triazolyl-2-cis-pen-3-thenol; 5-benzyloxy-2-(2',4'-dichlorophenyl)-1-triazolyl-2-trans-pen-3-thenol; 5-(4'-dichlorophenyl)oxy-2-(2',4'-dichlorophenyl)-1-triazolyl-2-trans-pen-3-thenol or 2-(2',4'-dichlorophenyl)-5-methoxy-1-triazolyl-2-cis-pen-3-thenol.

Description

Ether derivative of (substituted phenyl) -1H-1,2,4-triazol-1-ylalkenol and preparation method thereof

FIELD OF THE INVENTION The present invention relates to triazole derivatives useful as fungicides, and more particularly to ether derivatives of (substitutedyl) -1H-1,2,4-triazol-1-ylalkenol, methods for preparing the same and for combating plant pathogens. To its use.

European Patent Application No. 332,387 (published Sep. 13, 1989) by Oida et al. Describes extensively about (halophenyl) -1H-1,2,4-triazol-1-ylalkanol and its bactericidal activity. The compound represented by the following general formula (A) is also mentioned.

However, the ether compounds of the present invention having a high bactericidal activity against plant pathogens are not dealt with at all.

Wherein Ar is a substituted or unsubstituted phenyl group, R ¹ is C ₁ -C ₆ alkyl, halo-C ₁ -C ₆ alkyl, substituted or unsubstituted phenyl, naphthyl or heterocyclyl; X is C ₁ -C ₆ alkylene, C ₂ -C ₆ aliphatic hydrocarbon with 1 or 2 double or triple bonds, C ₃ -C ₆ cycloalkylene, Y is hydrogen, NR ₂ CO, NR ₂ COCH : CH, O ₂ C, O ₂ CCH: CH and the like, wherein R ₂ is H, alkyl of C ₁ -C ₄ , and m and n represent 0 or 1.

The present invention is an ether derivative of (substituted phenyl) -1H-1,2,4-triazol-1-ylalkenol represented by the following general formula (I), a new type of triazole type fungicide, isomers thereof and agronomically acceptable To give his acid addition salt.

Wherein X ¹ and X ² each independently represent hydrogen, halogen or an alkoxy group of C ₁ -C ₃ , and R ¹ represents ethylene or ethynylene; R ² is C ₁ -C ₆ alkyl; C ₂ -C ₄ alkenes; C ₂ -C ₄ alkyne; Aryl unsubstituted or substituted with halogen, hydroxy or C ₁ -C ₃ alkyl groups; Or 5-6 membered heterocycloalkyl containing at least one atom such as oxygen or nitrogen in the ring.

The term alkenol used in the name of the above general formula (I) compound refers to an alcohol having an unsaturated bond such as a double bond or a triple bond in the chain.

Representative examples of alkoxy include methoxy, ethoxy, propoxy or isopropoxy and the like.

The term alkyl refers to both branched or straight chain alkyl having carbon atoms, representative examples of which are methyl, ethyl, n-propyl, isopropyl, n-butyl, sec-butyl, isobutyl, t-butyl, pentyl, neo-pentyl , Hexyl, heptyl and the like.

The term alkene means a C ₂ -C ₄ unsaturated hydrocarbon having at least one double bond, representative examples of which are ethenyl, 1-propenyl, isopropenyl, allyl, 1-, 2- or 3-butenyl , 1,3-butadiene and the like.

The term alkyne refers to a C ₂ -C ₄ unsaturated hydrocarbon having at least one triple bond, representative examples of which are ethynyl, 1-propynyl, 2-propynyl, 1-, 2- or 3-butynyl, 1-butene-3-ynyl and the like.

The term aryl refers to a 5-6 membered aromatic hydrocarbon substituted or unsubstituted with a halogen atom such as fluorine or chlorine, a hydroxy group, a C ₁ -C ₃ alkyl group, and representative examples thereof include phenyl, 4-chlorophenyl, 2,4-dichlorophenyl, 2-chloro-6-fluorophenyl, 3-methylphenyl and the like.

Preferred examples of heterocycloalkyl are pyridine, pyran, imidazole, triazole and the like.

Among the compounds of the general formula (I) according to the present invention, when R ¹ is ethylene, it includes both cis- or trans-isomers.

As the acid addition salt of the compound of the general formula (I) according to the present invention, for example, hydrochloric acid, bromic acid, sulfuric acid, fluoric acid, sulfonic acid, acetic acid and the like are suitable.

Hereinafter, typical compound (I) of this invention is shown in following Table 1.

TABLE 1

The compound of formula (I) according to the present invention can be prepared according to the following reaction scheme from the compound of formula (II).

Scheme

Wherein X ¹ , X ² , R ¹ and R ² are the same as described above.

Hereinafter, the manufacturing method according to the present invention will be described in more detail.

First, the compound of formula (II) is reacted with triazole in the presence of a solvent and a base to give a compound of formula (I-a) wherein substituent R ¹ is ethynylene. At this time, the amount of triazole is preferably 1 to 5 mole times based on the general formula (II) compound.

The reaction temperature may range from room temperature to 200 ° C., preferably 60 to 100 ° C., and a reaction time of 3 to 20 hours is appropriate. Bases in the reaction include alkali metal hydroxides such as sodium hydroxide and potassium hydroxide; Alkali metal carbonates such as sodium carbonate, potassium carbonate and the like or conventional organic amines such as triethylamine, pyridine and the like are used, of which sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate is particularly preferred. The use amount of these bases may be 1 to 10 mole times with respect to the compound of general formula (II), but preferably 2 to 5 mole times. As the solvent of this reaction, a polar solvent such as DMF (dimethylformamide), acetonitrile, DMSO (dimethylsulfoxide) or the like is used, and the amount thereof is used in an amount of 1 L to 10 L per mole of the compound of formula (II).

On the other hand, when the compound of the general formula (I-a) prepared by the above reaction is reduced with a metal hydride, a compound of the general formula (I-b) in which the substituent R ¹ is trans-ethenylene is prepared. In this case, as the metal hydride, aluminum (A1) hydride, boron (B) hydride or tin (Sn) hydride is preferably used. The amount of the metal hydride used is preferably 2 to 4 mol times based on the general formula (II) compound. As the solvent for this reaction, a conventional hydrocarbon solvent or an ether solvent such as tetrahydrofuran (THF) is used, and the reaction temperature is 0 to 100 ° C.

In addition, when the hydrogenation reaction of the compound of formula (I-a) is carried out in a solvent using a transition metal catalyst, a compound of formula (I-c) in which the substituent R ¹ is cis-ethenylene may be prepared. In this case, the transition metal catalyst may be nickel (Ni), cobalt (Co), zinc (Zn), palladium (Pd) or the like alone, but a transition such as Lindlar Catalyst (Pd-Pd-CaCO ₃ ). Particular preference is given to using complexes of metals, the reaction temperature being in the range of 0 to 100 ° C.

The compound of formula (II) used as a starting material in the present invention can be easily prepared from the compound of formula (III) and the compound of formula (IV).

Wherein X ¹ , X ² and R ² are the same as described above, and M is selected from the group consisting of transition metal, metal lithium and magnesium halide.

The reaction is carried out at a temperature of -100 to 50 ℃, wherein a solvent may be a hydrocarbon solvent or an ether solvent, preferably an ether solvent is preferred, tetrahydrofuran is particularly preferred.

The compound of general formula (I) according to the present invention shows high activity against plant pathogens, and may be used as an active ingredient of agricultural or horticultural fungicides. Looking at the usefulness of the compound of formula (I) according to the present invention.

Fungi for Paddy Crops, Pyricularia oryzae, Cochlioblus miyabeanus, Rhizoctonia solani.

Fungi for crops, Erysiphe graminis, f.SP. Hodai (f.SP.hordeil), f.SP. Tritici, Gibbella zeae, Puccinia striormis, P. graminis, P. recodita, P. hordei Typhula sp., Mictonectriella ni-valis, Ustilago tritici, U. nuda. nuda, Tilletia caries, Pseudocercosporella herpotri-choides, Rhynchosporium secalis, Septoria tritici, Leptosperia node Room (Leptosphaeria nodorum).

Fungi for citrus fruits, Diaporthe citri, Elsinoe fawcetti, Penicillium digitatum, P. italicum.

Fungi for apples, Slclerotinica mail, Valsa mail, Podsphaera leucotricha, Altemaria mail, Venturia inaequalis ).

Bacillus fungi, Venturia nashicola, V. pirina, Alteraria kikuchiana, Gymnosporangium haraeanum.

Fungi for grapes, Elsinoe ampelina, Glomerella cingulata, Uncinula necator, Phakopsora ampelopsidis, Gignardia bead Walligna (Guignardia bidwellii), Plasmopara viticola.

Fungi for cucumbers, Colletotrichum lagenarium, Sphaerotheca fuliginea, Mycosphaerella melonis, Pseudoperonospora cubensis, Pitophthora sp. (Phytophthora sp.).

Fungi for tomatoes, Alternaria solani, Cladosporium fulvum, Phytophthora infestans.

Fungi for soybeans, Cecosopora kikuchii, Elsinoe glycines, Diaporthephaseolorum varsojae, Colletotrichum lindemthianum and various other crops Pycurulari duck, which exhibits excellent bactericidal activity against Botrytis cinerea and Sclerotinia sclerotiorum, which causes disease in (Pyricularia oryzae), Botrytis cinerea, and Erysiphe gramins, a pathogen for wheat, have excellent effects.

In order to use the compound represented by the general formula (I) as a bactericide, these compounds themselves or a mixture thereof and a carrier may be prepared as a powder, a hydrateable powder, a granule, an emulsion concentrate, a liquid, and the like. In addition, if desired, it is possible to add a desired effect by adding auxiliaries such as dispersants, emulsifiers, wetting agents, and caking agents, which are commonly used in the agricultural field, in addition to the carrier.

Hereinafter, the present invention will be described in more detail based on synthetic and biological examples, but the technical scope of the present invention is not limited to the following examples unless the main characteristics are changed.

Preparation Example 1

Synthesis of 1-chloro-2- (2 ', 4'-dichlorophenyl) -5-methoxy-2-phen-3-tinol

600 mg of propargyl methyl ether is dissolved in 10 ml of tetrahydrofuran, and 3.84 ml of 2.23 M solution n-butyllithium is added dropwise at -30 ° C and stirred for 30 minutes. The reaction mixture was cooled to -78 ° C and then added dropwise to 30 ml of tetrahydrofuran solution containing 2.11 g of cesium trichloride (CeCl ₃ ) and stirred for 30 minutes while maintaining -30 ° C. After cooling the reaction mixture to -78 ° C, 500 ml of tetrahydrofuran solution in which 1.92 g of 2,4,2'-trichloroacetophenone is dissolved is added dropwise. Stir for 1 hour while maintaining at −30 ° C., then add 2-3 drops of methanol to complete the reaction. After completion of the reaction, the mixture was extracted with ethyl ether, washed sequentially with an aqueous ammonium chloride solution and water, dried over anhydrous forget-me-not and column chromatography to obtain 1.76 g (yield: 70%) of the title compound.

H ¹ NMR (CDCl ₃ ) δ: 7.84 (d, 1H), 7.42 (d, 1H), 7.31 (dd, 1H), 4.26 (d, 1H), 4.18 (s, 2H), 3.90 (d, 1H) , 3.40 (s, 3H), 3.27 (s, 1H).

Preparation Example 2

Synthesis of 5-allyoxy-2- (2 ', 4'-dichlorophenyl) -1-chloro-2-phen-3-thiol

960 mg of propargyl allyl ether was used in the same manner as in Preparation Example 1 to obtain 2.4 g (yield: 72%) of the title compound.

Example 1

Synthesis of 5-allyoxy-2- (2 ', 4'-dichlorophenyl) -1-triazolyl-2-phen-3-thiol (5)

1.32 g of the compound obtained in Preparation Example 2, 860 mg of triazole and 1.72 g of potassium carbonate were added to 10 mg of DMF, followed by stirring at 80 ° C. for 16 hours. After the reaction, add ethyl acetate and wash with sodium chloride aqueous solution and water. After drying over anhydrous forget-me-not, the solvent was removed under reduced pressure and column chromatography gave 1.14 g (yield: 78%) of the title compound.

H ¹ NMR (CDCl ₃ ) δ: 8.22 (s, 1H), 7.96 (s, 1H), 7.81 (d, 1H), 7.51 (d, 1H), 7.33 (dd, 1H), 5.9 (m, 1H) , 5.42 (d, 1H), 5.29 (d, 1H), 4.98 (d, 1H), 4.70 (d, 1H), 4.19 (s, 2H), 4.01 (d, 2H), 3.53 (d, 1H).

Example 2

Synthesis of 2- (2 ', 4'-dichlorophenyl) -5-methoxy-1-triazole-2-phen-3-thiol (6)

As a starting material, 1.01 g (yield: 75%) of the title compound was obtained in the same manner as in Example 1 except that 1.21 g of the compound obtained in Preparation Example 1 was used.

H ¹ NMR (CDCl ₃ ) δ: 8.15 (s, 1H), 7.94 (s, 1H), 7.77 (d, 1H), 7.45 (d, 1H), 7.27 (dd, 1H), 4.94 (d, 1H) , 4.93 (s, 1H), 4.66 (d, 1H), 4.07 (d, 1H), 3.28 (s, 3H).

Example 3

Synthesis of 2- (2 ', 4'-dichlorophenyl) -5-methoxy-1-triazolyl-2-cis-phen-3-thiol (12)

260 mg of the compound obtained in Example 2 is placed in 10 ml of acetone together with 10 mg of linden and a catalyst, and hydrogen is passed through until the reaction is completed. After the reaction was completed, the reaction mixture was diluted with ethyl acetate and washed sequentially with aqueous sodium chloride solution and water. Drying over anhydrous forget-me-not, the solvent was removed under reduced pressure, and then chromatographed to give 165 mg (yield: 65%) of the title compound.

H ¹ NMR (CDCl ₃ ) δ: 8.14 (s, 1H), 7.82 (s, 1H), 7.70 (d, 1H), 7.38 (d, 1H), 7.22 (dd, 1H), 7.37 (d, 1H) , 5.73 (t, 1H), 4.71 (ABq, 2H), 3.6 (m, 2H), 3.16 (s, 3H).

Example 4

Synthesis of 2- (2 ', 4'-dichlorophenyl) -5-methoxy-1-triazole-2-trans-phen-3-thiol (9)

250 mg of the compound obtained in Example 2 was dissolved, and 5 ml of THF solution was added dropwise to 5 ml of THF solvent and stirred at room temperature for 20 hours. 100 mg of aluminum hydride was added thereto and stirred for 8 hours to complete the reaction. In the same manner as in Example 3 below, 133 mg (yield: 53%) of the title compound were obtained.

H ¹ NMR (CDCl ₃ ) δ: 7.99 (s, 1H), 7.85 (s, 1H), 7.68 (d, 1H), 7.34 (d, 1H), 7.16 (dd, 1H), 6.31 (d, 1H) , 5.92 (dt, 1 H), 5.19 (d, 1 H), 4.78 (s, 1 H), 4.63 (d, 1 H), 3.92 (dd, 2H), 3.31 (s, 3H).

Compounds of general formula (I) shown in Table 1 above can be synthesized by carrying out a similar method as in Example 1. The physical properties of the synthesized compounds are shown in Table 2 below.

TABLE 2

Biological Example 1: Test of bactericidal power in vitro

The inhibition of mycelial growth was examined by containing the medicine in the medium containing the bacteria. The experimental drug was dissolved in acetone, ethyl alcohol, methyl alcohol, and the like, and the medium used potato textose medium (PDA, Difco), and the content of the organic solvent in the medium was not more than 1%. The pH of the medium was about 6-7, and the drug was prepared by mixing the ratio of the drug dissolved in the organic solvent and the medium at 1:90, and dispensed 5 ml each in a small petri dish (60 × 15 m / m). Strains to be inoculated in the drug medium were advanced over 1 to 10 days depending on the growth characteristics of the most active state. After a certain incubation period according to the strain to compare the mycelial growth of the drug treatment group and mycelial growth of the untreated group to calculate the mycelial growth inhibition rate is shown in Table 3 below.

TABLE 3

Bactericidal assay against Pyricularia oryzae (PO) and Botrytis cinerea (BC) bacteria

* Note: ≥50% control at +: 250ppm

-: 50% control at 250ppm

Biological Example 2: In vivo Sterilization Test

The barley (variety: barley) used as host plants was sown 10 pots (ψ 5 × 5㎠) and used after a week in the greenhouse.

The subject drug was prepared at a predetermined concentration using acetone tart-20 (250ppm) and sprayed sufficiently (about 2ml / pot) so that the drug did not fall off the leaves using a small atomizer. After 24 hours of air-dried barley, treated with barley powdery mildew (Erysiphe graminis: EG) spores in subculture, induces the disease at 20 ℃, constant conditions (50 to 60% RH), after 10 days The control value calculated by comparing with the treatment area was calculated in the incidence area ratio is shown in Table 4 below.

TABLE 4

Bactericidal test against barley powdery mildew

* Note: ≥50% control at +: 250ppm

-: 50% control at 250ppm

Claims (11)

Ether derivatives of novel (substituted phenyl) -1H-1,2,4-triazol-1-yl alkenol represented by the following general formula (I), isomers thereof and agriculturally acceptable acid addition salts thereof. Wherein X ¹ and X ² each represent halogen; R ¹ represents ethylene or ethynylene; R ² represents C ₁ -C ₆ alkyl, C ₂ -C ₄ alkenes, phenyl, benzyl or tetrahydropyranyl unsubstituted or substituted with halogen. 2. The compound of claim 1 further comprising: 2- (2 ', 4'-dichlorophenyl) -5- (pyran-2'-yl) oxy-1-triazolyl-2-phen-3-tinol; 2- (2 ', 4'-dichlorophenyl) -5-phenoxy-1-triazolyl-2-phen-3-tinol; 5- (4'-chlorophenyl) -oxy-2- (2 ', 4'-dichlorophenyl) -1-triazolyl-2-phen-3-tinol; 2- (2 ', 4'-dichlorophenyl) -5- (2', 2'-dimethylpropyl) oxy-1-triazolyl-2-phen-3-tinol; 5-allyloxy-2- (2 ', 4'-dichlorophenyl) -1-triazolyl-2-phen-3-tinol; 2- (2 ', 4'-dichlorophenyl) -5-methoxy-1-triazolyl-2-phen-3-tinol; 5-benzyloxy-2- (2 ', 4'-dichlorophenyl) -1-triazolyl-2-phen-3-tinol; 5-allyloxy-2- (2 ', 4'-dichlorophenyl) -1-triazolyl-2-trans-phen-3-tinol; 2- (2 ', 4'-dichlorophenyl) -5-methoxy-1-triazolyl-2-cis-phen-3-tenol; 5-benzyloxy-2- (2 ', 4'-dichlorophenyl) -1-triazolyl-2-trans-phen-3-tenol; 5- (4'-dichlorophenyl) oxy-2- (2 ', 4'-dichlorophenyl) -1-triazolyl-2-trans-phen-3-tenol or 2- (2', 4'-dichlorophenyl The compound of general (I) which is) -5-methoxy-1-triazolyl-2-cis-phen-3-tenol. A process for preparing a compound of formula (I-a), characterized by reacting a compound of formula (II) with triazole in the presence of a solvent and a base. Wherein X ¹ and X ² each represent a halogen; R ¹ represents ethylene or ethynylene; R ² represents C ₁ -C ₆ alkyl, C ₂ -C ₄ alkenes, phenyl, benzyl or tetrahydropyranyl unsubstituted or substituted with halogen. The method of claim 3 wherein the base is sodium hydroxide, potassium hydroxide, sodium carbonate or potassium carbonate. The method of claim 3 wherein the solvent is DMF, acetonitrile or DMSO. The method of claim 3, wherein the reaction temperature is 60 to 100 ℃. A process for producing a compound of formula (I-b), characterized in that the compound of formula (I-a) is reduced to a metal hydride. Wherein X ¹ and X ² each represent halogen; R ¹ represents ethylene or ethynylene; R ² represents C ₁ -C ₆ alkyl, C ₂ -C ₄ alkenes, phenyl, benzyl or tetrahydropyranyl unsubstituted or substituted with halogen. 7. The method of claim 6, wherein the metal hydride is aluminum (Al) hydride, boron (B) hydride or tin (Sn) hydride. A process for preparing the compound of formula (I-c), wherein the compound of formula (I-a) is hydrogenated using a transition metal catalyst. Wherein X ¹ and X ² each represent halogen; R ¹ represents ethylene or ethynylene; R ² represents C ₁ -C ₆ alkyl, C ₂ -C ₄ alkenes, phenyl, benzyl or tetrahydropyranyl unsubstituted or substituted with halogen. 10. The process of claim 9 wherein the transition metal catalyst is a Lindla catalyst. A fungicide composition comprising the compound of formula (I) as defined in claim 1 together with a conventional carrier.