JPS6212762A - Imidazole derivative - Google Patents

Abstract

NEW MATERIAL:An imidazole derivative expressed by formula I (R is 6-9C straight chain alkyl) and an acid addition salt thereof. EXAMPLE:1-[1-(2-n-Hexyloxyphenyl)-1-propenyl]-1H-imidazole. USE:Useful as an industrial germicide and capable of exhibiting excellent germicidal power and wide antimicrobial spectrum for many germs causing deterioration in industrial materials, products, etc., particularly Cladosprosium herbarum deteriorating paints, latexes, rubber raw materials, etc., Chaetomium globosum. etc., degteriorating fibers, plastics, paper, etc., and exhibiting remarkable effect on molds, e.g. molds of the genus Alternaria, and stable to light, heat and oxidation. PREPARATION:2-Hydroxyphenyl ethyl ketone is reacted with compounds expressed by formula II and formula III (X is reactive group) synthesized from N,N'-thionyldiimidazole to afford the aimed compound expressed by formula I.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention provides an imidazole derivative represented by the general formula (1) (wherein R represents a straight-chain alkyl group having 6 to 9 carbon atoms) The present invention relates to an acid addition salt thereof and an industrial fungicide characterized by containing the acid addition salt thereof as an active ingredient.

[Prior art]

Conventionally, industrial fungicides have been added to household or various industrial products, such as emulsion paints, organic adhesives, wall covering materials, textiles, plastic products, or their raw materials, or they have been added to suitable dispersion media. By dissolving or dispersing an industrial fungicide in the solution and applying it, antibacterial and antifungal effects are imparted to these products or the surfaces to be coated. Inorganic or organic compounds of heavy metals such as mercury, tin, copper, etc. have been widely used as industrial disinfectants, but although these compounds have excellent disinfecting effects, they are highly toxic to humans and livestock (and pose problems during use). Not only that, but there is a great risk that it may remain in the used product and cause secondary damage, and it is also unsuitable for use due to the environmental pollution problems caused by wastewater, waste, etc. Non-metallic fungicides that have been introduced in China are not effective against bacteria or fungi, as they are only effective against a limited number of fungi or have a limited range of use, and often cause contamination or deterioration of industrial materials or products. There are cases where it cannot be prevented.

For example, benzimidazole compounds, which are considered to be the best among non-metallic fungicides, contain Aspergillus, which grows in paints, pastes, wood and bamboo products, textiles, etc. and causes deterioration.
, Penicillium , Trichoderma , and other molds show excellent antibacterial activity when diluted with an agar medium.

However, Alternaria (Alternaria), which occurs on the coating surface of emulsion paint, artificial leather, cross walls, etc.
a) It does not show antibacterial activity against molds such as Mucor. Also, it shows no antibacterial activity against bacteria. Furthermore, it can be used in a wide variety of practical situations, such as coatings,
When used for antibacterial and fungicidal purposes such as wall covering materials or wood and bamboo products, it has the disadvantage that no effect can be expected at practical concentrations (1100-500 pp). Therefore, there is a strong demand for the development of industrial fungicides that are safe and easy to use, exhibiting outstanding effects at practical concentrations.

[Problem to be solved by the invention]

An object of the present invention is to overcome the drawbacks of conventional industrial disinfectants as described above and to provide an industrial disinfectant having extremely excellent properties. In other words, by adding a low dose of
It is an object of the present invention to provide a highly safe industrial disinfectant that can completely and over a long period of time control a wide variety of fungi that occur in industrial materials and products and cause contamination.

[Means and effects for solving the problem] In order to solve the above problem, a large number of imidazole derivatives were synthesized and antibacterial tests were conducted. As a result, imidazole derivatives represented by the general formula (1) (wherein R represents a straight-chain alkyl group having 6 to 9 carbon atoms) and their acid addition salts can cause deterioration of industrial materials and products. (These compounds exhibited excellent bactericidal activity and a broad antibacterial spectrum against many fungi.Furthermore, these compounds were added to industrial materials and products, such as paints, latex, and plasterboard, to conduct mold resistance tests.) However, it has been found that the compound of the present invention has extremely excellent performance as an industrial fungicide.

The compound of the present invention is a new substance unknown in the literature. Compounds similar to the compounds of the present invention include general formula (1) in which R is an alkyl group having 1 to 5 carbon atoms, ie, methyl, ethyl,
propyl, isopropyl, butyl, 5ec-7'thyl,
Imidazole derivatives having pentyl and impentyl groups and acid addition salts thereof are disclosed in Japanese Patent Publication No. 56-39073.
Disclosed in the issue.

This prior art includes an in vitro antibacterial test example for one compound, that is, a compound in which R is a methyl group (Aspergillus fumigate, a fungus that infects living organisms).
illus fumigates), Candida albicans (Candida albicans), Trichutes, Iton asteroides (
Trichophyton asteroi-des
) and Botrytis blight control test examples are shown, and these compounds are shown to be
・Or as an antifungal agent for animals or a fungicide for agriculture.
1: It is suggested that it is effective. However, this prior art does not include whether these compounds have antibacterial activity against a wide variety of fungi that cause contamination of industrial materials or products, and whether they are actually added to industrial materials or products. The antibacterial and antifungal activity of
1.: Not even suggested.

According to the present invention, as a compound which is a highly active and useful industrial fungicide, in the general formula (1), R has 6 to 9 carbon atoms.
Imidazole derivatives and acid addition salts thereof are provided which are linear alkyl groups limited to the range of . The compound of the present invention has specifically superior antibacterial activity against mold that is a source of contamination of industrial raw materials or products compared to other alkyl chain compounds, and in general formula (1), R is an alkyl group having 1 to 5 carbon atoms. It has an unexpectedly outstanding antibacterial activity of 5 to 100 times, and a broad antibacterial spectrum, both in comparison with certain known compounds mentioned above, and in comparison with compounds in which R is an alkyl group having 10 or more carbon atoms. . The compound of the present invention is particularly suitable for Cladosporium helvarum (Cladosp.
orium herbarum), Chaetomium globosum, which degrades textiles, plastics, paper, pulp, etc.
Aureobasidium pullulans causes deterioration of wood, paint, packaging materials (aluminum foil, plastic, paper, etc.), etc.
It exhibits extremely strong antibacterial activity against fungi such as A. la-ns). In addition, the compound of the present invention is a benzimidazole compound that is currently a typical commercially available industrial fungicide, 2-(4-thiazolyl)benzimidazole (hereafter T
It exhibits far superior antibacterial activity than BZ (sometimes abbreviated as BZ). In addition, the compound of the present invention is highly effective against fungi such as Alternaria, for which the development of an effective agent is highly desired. In addition, the compound of the present invention has an extremely broad antibacterial spectrum and has strong antibacterial activity against bacteria for which the known compounds exhibit little antibacterial activity.In particular, Ω contamination of cutting oil and emulsion latex is a problem, making it difficult to control. Eschri
It also shows strong antibacterial activity against Gram-negative bacteria such as chia coli. This can be said to be an extremely superior feature compared to the fact that TBZ is resistant to bacteria (it does not exhibit antibacterial properties and can only be used as a fungicide).

As mentioned above (the compound of the present invention has excellent properties as an industrial disinfectant, it can be used in general industrial products such as paints, glues, wood and bamboo products, leather, textiles, wall covering materials, resin emulsions, adhesives, cooling It can be used in a wide range of fields, including lubricants and plastic products that break down when attacked by microorganisms.

The compound (1) of the present invention is synthesized by the method described below.

(II) (1) (cis,
trans mixture) (cis, trans mixture) (wherein, X
represents a reactive group (for example, a halogen, an ester residue such as tosyl), and R represents a straight-chain alkyl group having 6 to 9 carbon atoms. ) That is, the compound of the present invention comprises a synthetic intermediate (II) that can be easily synthesized from 2-hydroxyphenylethyl ketone and N,N'-thionyldiimidazole;
It can be easily obtained by a method of reacting a synthetic raw material (Ill) in the presence of a base. Examples of the base used include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride, potassium hydride, sodium alcoholade, sodium amide, pyridine, and triethylamine. The reaction is carried out in a suitable inert solvent such as dimethylformamide, benzene, toluene, methanol,
It is carried out in chloroform, dimethyl sulfoxide, or tetrahydrofuran at room temperature or under heating. The reaction temperature is 15
The temperature can be appropriately selected from between 150°C and 150°C.

The target substance (I) thus obtained can be converted into an acid addition salt, if necessary. Forming such salts are octacid, uL"t"fermentic acid'"'acid, octacacid, υ'"'
Organic acids such as j-acid, succinic acid, oxalic acid, and maleic acid
, acids and inorganic acids such as hydrohalic acid, sulfuric acid, nitric acid, and phosphoric acid.
゛The compound of the present invention is usually prepared in the form of a preparation supported on a carrier, such as an oil solvent, emulsion, paste, powder, wettable powder, aerosol, or
Used in the form of anti-fungal paints, etc.

The liquid carrier used in the formulation of the compound of the present invention may be any liquid as long as it does not react with the active ingredient, such as water, alcohols (methanol, ethanol, ethylene glycol, propylene glycol, etc.), ketones (
acetone, methyl ethyl ketone, etc.), ethers (dioxane, tetrahydrofuran, cellosolve, etc.), aliphatic hydrocarbons (kerosene, gasoline, etc.), aromatic hydrocarbons (benzene, toluene, xylene, etc.), halogenated hydrocarbons (chloroform, etc.) , dichloroethane, etc.), acid amides (dimethylformamide, etc.), esters (acetic acid ethyl ester, etc.), organic bases (pyridine, etc.), nitriles (acetonitrile, etc.), diethylene glycol monomethyl ether, diethylene glycol monoethyl ether, etc. can. other,
Inorganic solid carriers such as clay, talc, bentonite, and kaolin, and gas carriers such as dimethyl ether and chlorofluorocarbon gas can also be used.

If necessary, an ionic or nonionic surfactant, a polymer compound such as vinyl acetate, methyl cellulose, etc. can be used in combination as an auxiliary agent to further enhance the formulation effect. In addition, when the compound of the present invention is applied as an industrial fungicide, it may also be used with other fungicides, fungicides, or other agricultural chemicals, such as insecticides, fungicides, acaricides, herbicides, plant growth regulators, fragrances, etc. It can also be used in combination with or as a mixture.

The disinfectant of the present invention can be treated by impregnating, coating, or mixing with the base material depending on the characteristics and usage conditions of houses, fittings, furniture, household goods, various industrial products, and raw materials. I can do it. For example, walls and ceilings in ordinary homes,
It is ideal as an antibacterial and fungicidal agent for tatami mats, floors, carpets, furniture, etc., and for many general industrial raw materials and products such as paints, resins, pastes, adhesives, wood and bamboo products, and leather.

〔Example〕

Hereinafter, the present invention will be explained in more detail according to Examples, Formulation Examples, and Test Examples, but the scope of the present invention is not limited by these in any way.

Intermediate 1-[1-(2-
A method for producing hydroxyphenyl)-1-7'ropenyl]-IH-imidazole is shown as a reference example.

Reference Example Imidazole 60 SL (0.88 mol) In a solution consisting of 300 ml of dry methylene chloride, thionyl chloride 26.2% (0.2
2 mol) was gradually added dropwise. After continuing stirring for another 10 minutes, 2-hydroxyphenylethyl ketone 245)-(0.16 mol) was gradually added while keeping the reaction solution at a temperature around 20°C. After continuing stirring at room temperature for 30 minutes, the solvent was removed under reduced pressure at a temperature below 40°C. An aqueous potassium carbonate solution (K, Co, 45°51.0.33 mol, water 140 ml) was gradually added to the residue under water cooling.

After removing P from the solid obtained here, it was thoroughly washed with water and then acetone to obtain a pale yellow solid (II) 27.2'/(y
, 84.9%, mp, 151-152°C).

NMR 6,34 (IH, m), 6.68-7.24 (6H
.

m), 7.50-7.60 (IH, m), 9.
70(IH,s) Example 1 1-(1-(2-n-hexyloxyphenyl)-1
-propenyl)-1H-imidazole Dissolve the solid (II) 2.6 P (0,013 mol) obtained in the previous reference example in 15 ml of dry dimethylformamide,
1.2 y-(0,018 mol) of 5.5% potassium hydroxide was added under ice cooling. After continued stirring at room temperature for 15 minutes, 1.6 P (0,013 mol) of 1-chlorohexane
was added and reacted at 40 to 50°C for 5 hours. Ice water was added to this reaction solution, and extraction was performed with toluene. The organic layer was washed with water, dried over anhydrous sodium sulfate, and the toluene was distilled off.
The residue was subjected to column chromatography on silica gel and eluted with 30% ethyl acetate-n-hexane. The eluate was concentrated and the oily substance (1) 3.505i' (y,
95%).

NMRt 1.56 (8H, m); 1.63-1.86 (3H
.

m); 3.72-4.20 (2H, m); 5.
76-5.96 (IH, m); 6.80-7.42
(7H, m) Elemental analysis result CHN Calculated value (%) 76.06 8.45 9.86 Actual value (%) 76.13 8.38 9.80 In addition, hydrochloric acid was added to the above oily substance (1) 151'- Ethanol was added and concentrated, and the remaining amount was recrystallized from methanol-acetic acid to obtain 0.95P of hydrochloride. Melting point: 100-102°C Examples 2-6 The products listed in Table 1 were obtained in the same manner as in Example 1.

Formulation example 1 Compound of the present invention 5 70 parts Neugen E
A-8730 parts (surfactant manufactured by Daiichi Kogyo Seiyaku ■) The above ingredients were mixed uniformly to form an emulsion.

Formulation Example 2 Compound 2 of the present invention 20 parts Neugen E
A-877 parts (surfactant manufactured by Daiichi Kogyo Seiyaku ■) Emar 10 (surfactant manufactured by Kao ■) 1 part water
72 parts or more are uniformly mixed to form a suspension.

Formulation Example 3 Compound 3 of the present invention 20 parts Tulpol AC-315310 parts (surfactant manufactured by Toho Chemical Co., Ltd.) Propylene glycol 15 parts Water
55 parts or more are uniformly mixed to form a suspension.

Formulation Example 4 Oxalate of Compound 3 of the Invention 20 parts Emal 10 (surfactant manufactured by Kao ■) 5 parts Emulgen 920 (
) 5 parts Clay 70 parts or more are crushed and mixed uniformly to prepare a wettable powder.

Formulation Example 5 Compound of the present invention 1 1 part propylene glycol 6 parts 99% ethanol
83 parts Freon gas
Mix at least 10 parts uniformly to make a spray.

Test Example 1 Antibacterial Activity Evaluation Test Antibacterial activity was evaluated by the agar dilution method. That is, the compound of the present invention is added to Potato dextrose aga
r The mixture was mixed into the medium at a graded concentration of 0.08 to 50 ppm, stirred well, and then poured into an IJ dish to form an agar plate. After the agar had solidified, a pure culture of the test bacteria was inoculated, and the bacteria were cultured at 30°C for 3 days, and the fungi were cultured at 25°C for 7 days, and then evaluated. The minimum concentration of the test compound contained in the medium in which the inoculated bacteria do not grow is defined as the minimum inhibitory concentration (Mxc
, ppm) in Table 2.

The names of the test bacteria are as follows.

Bacterial name Abbreviation: Aspergillus niger
'A, n.

Penicillium citrinum
P, c.

Cladosporium herbarum
C, h.

Chaetomium globosum
C, g. Trichoderma viride
T.v.

Aureobasidium pulluJans
) A, p.

Gibberella fujikuroi
G-f.

Alternaria Alternaria (Alternaria alternata)
a + Staphylococcus aureus (5taphlococcus aureus)
S, a.

Next, the fungicidal effect of the composition of the present invention in practical situations is as follows.
This will be explained in detail using the following test examples.

Trial M Example 2 (Mold resistance test for emulsion paint) The test method was based on the JIS-Z-2911r mold resistance test method. That is, 0.1% and 0.2% of each drug (20% formulation product) was added to acrylic emulsion paint (Vini Deluxe No. 300 manufactured by Kansai Paint Co., Ltd.).
Add and mix well. 0.11 of the drug-added paint was applied to each of the front and back sides of a filter paper with a diameter of 3 cIrL and air-dried. This filter paper was placed on an agar medium having the following composition and inoculated with a mixed spore suspension by spraying. The cells were cultured for two weeks at a temperature of 28° C. and a humidity of 95%.

The results indicate the degree of mold growth on the sample surface as shown below: -, ±.

Table-3
It was shown to.

−, No mold growth is observed on the sample surface±, Very slight mold growth is observed on a part of the sample surface+, Mold growth is clearly observed on a portion of the sample surface below approximately IA ++, Mold growth is observed on about 14 or more of the sample surface +++, Mold growth is observed on the entire sample surface 3; No mycelial growth is observed on the part inoculated with the sample or test piece.

2; The area of mycelial growth observed in the area inoculated with the sample or test piece does not exceed 1 area of the total area.

1; The area of mycelia growth observed in the area inoculated with the sample or test piece exceeds 14 of the total area.

Medium, water 10100O' Glucose 401 Peptone 10? Agar 251 Test bacteria, Aspergillus niger
Isniger) Penicillum citrinu+n Cladosporium herbarum Aureobasidium pullulans
Table 3≠1.2 and 3; 20% suspension TBZ; 2-(4-thiazolyl)-benzimidazole 20% emulsion; TBZ 20 parts Lactic acid 60 parts Neugen EA-875 parts Water 15 parts Test Example 3 (Building material Mildew resistance test of gypsum board) Cut gypsum board (Mitsui Toatsu Seibu Kenzai) into 5cIILX5 (m) pieces and soak in distilled water for 30 seconds. After taking it out, wipe off the water on the surface and leave it to dry for about 30 minutes. The drug (20% formulation product) was applied to the surface of this plasterboard at 1.0 and 2.
．． 0. and 4. Process oy-/rrl.

The above-mentioned gypsum board was placed on the test agar plate, and a mixed spore suspension of the test bacteria was spray inoculated. Temperature 28℃, humidity 95%
The cells were cultured for one month. The results are shown in Table 4, which is expressed in five levels as in Example 2, and the JIS standards (1, 2, 3) are also included.

Medium, water 10100O! Glucose 101 Peptone 0.5y'' Agar 25? Test bacteria: Aspergillus niger, Penicillium citrinum, Rhizopus 5tolonifer
! Cladosporium herbarum
'Aureobasidium pullulans
) Chaetomium globosum Fusarium moniliforme Table 4 TBZ; 2-(4-thiazolyl)-benzimidazole 1 Same formulation treatment as Test Example 2 [Effect of the invention] As is clear from the above explanation The compound of the present invention has a significantly stronger antibacterial activity of 5 to 100 times that of the known compound in which R in the general formula (1) is an alkyl group having 1 to 5 carbon atoms. It exhibits antibacterial activity far superior to that of the industrial disinfectant TBZ.

In addition, the compound of the present invention has an extremely broad antibacterial spectrum, and exhibits strong antibacterial activity against bacteria that the above-mentioned known compounds and TBZ do not exhibit antibacterial activity.
It is characterized by having high antibacterial activity even against Durham-negative bacteria such as A. coli.

Furthermore, even when disinfectants with high antibacterial activity are added to industrial materials and products, they often have problems such as no longer having an antibacterial and antifungal effect, insufficient sustainability, or deterioration such as discoloration. This may occur. However, as is clear from the test examples, the compounds of the present invention exhibit extremely high antibacterial and antifungal effects even when actually added to industrial products. Therefore, the compound of the present invention is an extremely excellent industrial fungicide that can provide excellent antibacterial and antifungal effects over a long period of time at a low dose, which is not expected to be effective with conventional commercially available agents.

Furthermore, the toxicity to humans and animals is extremely low (furthermore, there is no skin irritation or peculiar odor at practical concentrations, making it extremely safe to use).

In recent years, mold has been growing in homes, not only in relatively humid areas such as bathrooms and kitchens (but also in closets, large bags, etc.), not only detracting from the aesthetic appearance, but also mold spores being the cause of childhood bronchial asthma. There is a strong demand for a method to prevent this.The compound of the present invention is extremely safe, so
General industrial raw material.

It is extremely useful not only for products but also for mold prevention measures in the home.

Claims (2)

[Claims] (1) General formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (cis, trans mixture) (I) (In the formula, R represents a straight chain alkyl group having 6 to 9 carbon atoms.) Imidazole derivatives and acid addition salts thereof. (2) General formula (I) ▲ Numerical formulas, chemical formulas, tables, etc. are available ▼ (Mixture of cis and trans forms) (I) (In the formula, R represents a straight-chain alkyl group having 6 to 9 carbon atoms.) An industrial disinfectant containing an imidazole derivative represented by the formula and its acid addition salt as an active ingredient.