JPS6216404A - Industrial antifungal composition - Google Patents

Abstract

PURPOSE:The titled safe composition, containing one of a benzimidazole based compound and 2-n-octyl-4-isothiazolin-3-one as a novel imidazole derivative and capable of inhibiting the growth of various molds for a long period with a small amount of chemical. CONSTITUTION:An industrial antifungal composition containing at least one of 2-(4-thiazolyl)-benzimidazole, 2-n-octyl-4-isothiazolin-3-one and lower alkyl 2-benzimidazolecarbamate and one or more novel imidazole derivatives expressed by formula I (R1 is 6-9C straight chain alkyl; both R2 and R3 are H or together form methylene or alkylmethylene) or an acid addition salt thereof as active constituents. The mixing molar ratio of the fomer component to the latter component is preferably within 50/1-1/100 range. The compound expressed by formula I is synthesized by reacting a compound expressed by formula II with a compound expressed by formula III (X is reactive group) in the presence of a base.

Description

Detailed Description of the Invention [Industrial Application Field] The present invention relates to 2-(4-thiazolyl)-benzimidazole, 2-n-octyl-4-isothiazolin-6-one and 2-benzimidazole carbamic acid lower At least one alkyl ester and the general formula (1) (wherein R represents a straight chain alkyl group having 6 to 9 carbon atoms, R2 and R3 both represent a hydrogen atom or are combined) The invention relates to an industrial antifungal composition characterized by containing one or more imidazole derivatives represented by (representing methylene or alkylmethylene groups) or acid addition salts thereof.

[Prior Art] - Conventionally, antibacterial and antifungal agents have been added to household or various industrial products, such as emulsion paints, organic glues, wall coverings, textiles, plastic products, or their raw materials. Or, by dissolving or dispersing an antibacterial and fungicidal agent in a suitable dispersion medium and applying the solution, it is possible to impart an antibacterial and antifungal effect to these products or the surfaces to be coated. Inorganic or organic compounds of heavy metals such as mercury, tin, and copper have been widely used as antibacterial agents, but although these compounds have excellent bactericidal effects, they are highly toxic to humans and animals, causing problems when used. Furthermore, there is a great risk that they may remain in the used products and cause secondary damage, and they are also unsuitable for use because of the pollution problems such as environmental pollution caused by wastewater and waste. The non-metallic fungicides that have replaced these fungicides are not effective against only a few types of mold or have a limited scope of use, and are often used to contaminate industrial materials or products. Alternatively, changes in quality such as deterioration occur.

For example, the above benzimidazole compounds and 2-n
-Octyl-4-isothiazolin-6-one is a paint,
Aspergillus occurs in starch materials, wood and bamboo products, textiles, etc. and causes deterioration of their quality.
, Penicillium.

It exhibits excellent antibacterial activity against molds such as Trichoderma using the agar medium dilution method.

However, coating surface 1 of emulsion paint is artificial leather.

Alternaria that occurs on cross walls etc.
-aria), Mucor, and other molds have no antibacterial activity. Furthermore, when used in a wide variety of practical situations, such as for preventing mold on paint films, wall covering materials, or wood and bamboo products, it has the disadvantage that it is completely ineffective at practical concentrations (1oo-sooppm).

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 fungicides as described above and to provide an industrial fungicide with extremely excellent properties. In other words, we provide a highly safe industrial fungicide that completely and over a long period of time inhibits the growth of a wide variety of molds that grow on industrial materials or products when added in low doses. That is the issue.

[Means and effects for solving the problem] In order to solve the above problem, various studies were conducted on a large number of compounds and combinations thereof. As a result, it was discovered that by combining two or more compounds as active ingredients, which do not exhibit sufficient antifungal effects on their own, an industrial antifungal composition with significantly synergistically enhanced efficacy can be obtained. , we have completed the present invention.

That is, the antifungal composition of the present invention is characterized by containing the following components A and B as active ingredients.

(1) Component A 2-(4-thiazolyl)-benzimidazole (hereinafter referred to as
2-n-octyl-4-isothiazolin-3-one (abbreviated as TBZ)
(hereinafter abbreviated as OTO) 2-benzimidazole One or more types of carbamic acid lower alkyl esters (2) One or more types of imidazole derivatives or acid addition salts thereof represented by the B component general formula (1) (in the formula, R is Represents a straight-chain alkyl group having 6 to 9 carbon atoms, R2 and R3 both represent a hydrogen atom, or combine to represent a methylene or alkylmethylene group.) Each compound of component A is highly safe and ζ Although it exhibits a growth inhibiting effect on many molds, it alone does not exhibit sufficient anti-fungal power to completely suppress molds that occur in the living environment.

The above-mentioned 2-benzimidazolecarbamic acid lower alkyl esters include lower alkyl esters having 1 to 4 carbon atoms of 2-benzimidazolecarbamic acid, e.g.
Methyl, ethyl, n-propyl, i-propyl, n-butyl, 1-butyl.

5ec-butyl, t-butyl ester, etc. are used.

Although the compound used as component B is a new compound, it is highly safe, and the pH of the industrial material products to which it is applied is
It can be used regardless of whether it is acidic or alkaline.

In addition, the antibacterial spectrum is wide, and Alternaria (Alte
rnaria), Mucor, etc.
Even against molds for which each compound of component A does not show any effect,
It has a high antifungal effect. However, in the living environment,
It may not show sufficient anti-fungal power when used alone.

In this way, the composition of the present invention can mutually increase the antifungal power and increase the antifungal spectrum by using a combination of two or more compounds, each of which does not exhibit a satisfactory effect as a fungicidal agent alone. It is highly effective against a wide variety of molds that occur in the living environment.

Specific examples of component B include 1-(1-(2-n-hexyloxyphenyl)vinylcou 1H-imidazole 1Ci-(2-n-hebutyloxyphenyl)vinylcou 1H-imidazole IC1-(2-r+-octyl oxyphenyl)vinylcou 1H-imidazole 1-(1-(2-n-octyloxyphenyl)-1-
Propenyl-1H-imidazole 1-CI-(2-n-
Nonyloxyphenyl) vinyl 1H-imidazole 1-[1-(2-n-nonyloxyphenyl)-1-propenyl 1H-imidazole 1-(2-n-octyloxybenzyl)-1H-imidazole, etc., and its acid Examples include addition salts. Here, examples of acids that can form salts include organic acids such as acetic acid, citric acid, tartaric acid, shiuric acid, and maleic acid, and inorganic acids such as hydrohalic acid, sulfuric acid, nitric acid, and phosphoric acid.

Component B of the composition of the present invention is synthesized by the method described below.

(It) (1) (wherein,
X represents a reactive group (for example, a halogen, an ester residue such as tosyl), R represents a straight chain alkyl group having 6 to 9 carbon atoms, and R2 and R3 both represent a hydrogen atom or a combined represents a methylene or alkylmethylene group. ) That is, the compound of the present invention is produced by combining a synthetic intermediate ([) that can be easily synthesized from 2-hydroxyphenylalkyl ketone or 2-hydroxybenzyl alcohol and N,N'-thionyldiimidazole, and the synthetic raw material (1) with a base. It can be easily obtained by a method of reacting in the presence of The bases used include sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate, sodium hydride, potassium hydride, sodium alcoholade, sodium amide,
Examples include pyridine and triethylamine, and the reaction is carried out in a suitable inert solvent, such as dimethylformamide, benzene, toluene, methanol, chloroform, dimethyl sulfoxide, tetrahydrofuran, at room temperature or under heating. The reaction temperature can be appropriately selected from 15 to 150°C. The target substance (1) thus obtained is converted into an acid addition salt by a conventional method, if necessary.

The mixing ratio of component A and component B in the fungicide of the present invention is not particularly limited, but the mixing ratio is basically 1 mol to 1 mol, and it is appropriate to change the mixing ratio to a desired ratio depending on the purpose. It is. A preferred ratio is component A/B in terms of molar ratio.
Ingredients are in the range of 50/1-1/100.

The fungicidal composition of the present invention can be applied directly, dispersed in a suitable carrier, or mixed with a suitable solid carrier depending on the purpose of use. Furthermore, if necessary, dispersants, suspending agents, spreading agents, penetrating agents, wetting agents, stabilizers, etc. are added to these to produce water conservancies, powders, fine granules, pastes, suspensions, etc. agent.

It may also be used in the form of a spray.

The liquid carrier used in the antifungal composition of the present invention includes:
Any liquid may be used as long as it does not react with the active ingredient, such as water, alcohols (methanol, etc.).

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, 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 be used. Also, clay.

Inorganic solid carriers such as talc, bentonite, kaolin, etc.
Gas carriers such as dimethyl ether and chlorofluorocarbon gas can also be used.

Furthermore, as adjuvants to further enhance the formulation effect, ionic and nonionic surfactants, as well as vinyl acetate,
A polymer compound such as methylcellulose can be used in combination. In addition, when the composition of the present invention is applied as a fungicide, other fungicides may also be used.

fungicides or other pesticides, such as insecticides, fungicides,
It can also be used in combination or as a mixture with acaricides, herbicides, fragrances, etc. Among these, preferred ones are more specifically 2.4.5.6°-tetrachloroisophthalonitrile, 4-chloro-m-cresol, 8
-Hydroxyquinoline copper.

Tetrahydro-6,5-dimethyl-2H-1,3,5-
Examples include thiadiazine-2-thione, 2-bromo-2-bromomethylgeltalonitrile, and the like.

The composition of the present invention can be applied to the characteristics and usage conditions of houses, fittings, furniture, household goods, various industrial products, and raw materials.

Accordingly, the composition can be treated by methods such as impregnating, coating, or blending with the substrate. For example, walls, ceilings, and floors in ordinary homes.

It is ideal as an antibacterial and fungicidal agent for 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 Test Examples and Examples, but the scope of the present invention is not limited by these in any way.

First, a method for producing the synthetic intermediate (n) of component B of the composition of the present invention will be shown as a reference example.

Reference example 1 l-(1-(2-hydroxyphenyl)vinyl]1H-
Synthesis of Imidazole Thionyl chloride 26.29 (0.22 mol) was gradually added dropwise to a solution of imidazole 6 Of (088 mol) and 300 ml of dry methylene chloride while keeping the reaction solution at a temperature of 20°C. After continuing stirring for another 10 minutes,
While keeping the reaction solution at a temperature around 20 DEG C., 0-hydroxyacetophenone 22f (0.16 mol) was gradually added. After continuing stirring at room temperature for 60 minutes, the solvent was removed under reduced pressure at a temperature below 40°C.

Potassium carbonate aqueous solution (x2co3455g, 03
3 mol, water 14 oml) was gradually added under ice-cooling. The solid obtained here was collected by filtration, thoroughly washed with water and then acetone, and a pale yellow solid (A) 253 f (y, 842
%, m, p, 151-152°C).

MR 6,87-7,23 (6H, m), 7.59 (IH,
S) Reference Example-2 Synthesis of 1-(1-(2-hydroxyphenyl)-1-propenyl]-1H-imidazole Imidazole 60 r
(0.88 mol) 26.2 r (0.22 mol) of thionyl chloride is gradually added dropwise to a solution consisting of 300 mA' of dry methylene chloride while keeping the reaction solution at a temperature of 20°C. After continuing stirring for another 10 minutes, 2-hydroxyphenylethyl ketone 24f (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. Add potassium carbonate aqueous solution to the residue (
033 mol of K2CO3455f and 14 ml of water were gradually added under water cooling. The solid obtained here was collected by filtration, washed thoroughly with water and then with acetate, and a pale yellow solid (E) was obtained.
272 P (y, 84.9%, m, p, 151
-152°C) was obtained.

MR DMS O-D δ (ppm); 1.54-1.72 (3H
, m), 5.92-6.34? MS (IH, m), 6.68-7.24 (6H, m),
7.50-7.60 (IH, m), 9.70 (
II (,S).

In a similar manner, 2-hydroxybenzyl alcohol Kara 1-(2/-hydroxybenzyl)imidazole (
m, p, 162-164°C).

Next, a synthesis example of component B of the composition of the present invention will be shown.

Synthesis Example-1 1-(1-(2-n-hexyloxyphenyl)vinylcy 1H-imidazole production method Solid (A) obtained in Reference Example 1 above 2.s? (0,
1113 mol) was dissolved in 10 g of dry dimethylformamide, and 0.7 mole of sodium thihydride (mineral oil suspension) was dissolved in 10 g of dry dimethylformamide.
t (0,018 mol) was added under water cooling and stirred. After 5 minutes 1-chlorohexane 1.6 f (0,01
5 mol) and stirred at 4 to 50°C for 5 hours. Ice water was added to the reaction solution, and the mixture was extracted with toluene. The organic layer is washed with water, dried over anhydrous sodium sulfate, and then toluene is distilled off.

The residue was subjected to column chromatography on silica gel and eluted with 30q6 ethyl acetate-〇-hexane. Concentrate the eluate to obtain an oily substance (1) at 3.30? (y.

92chi) was obtained.

(n) 1.5437 MR DC13 δ (ppm); 0.80-0.92 (3H,
m), 1.24-1.56? MS (8H, m), 3.80 (2H, t, J=6H
2), 5.05 (1H,s), 5.32 (I
H,s), 6.80-7.00 (4H,m).

7.14-7.44 (3H, m) Additionally, hydrochloric acid and ethanol were added to (1) 1f and concentrated, and the residue was recrystallized from methanol-acetic acid to obtain 1) hydrochloride (2) 092 f. . Melting point: 107-110°C.

Synthesis Example-2 1-(1-(2-n-hexyloxyphenyl)-1-
Solid (B) obtained in Reference Example 2 of the first half of the 7"lopenyl)-1H-imyl'y"-Luno production method 2.69 (0,01
5 mol) was dissolved in 15 mA' of dry dimethylformamide, and 1.29 (0,018 mol) of 855 potassium hydroxide was added under water cooling. After continued stirring at room temperature for 15 minutes, 1.6 f (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 extracted with toluene. After washing the organic layer with water and diluting it with anhydrous sulfuric acid, and drying with IJum, the toluene was distilled off.
The residue was subjected to column chromatography on silica gel and eluted with 30 ethyl thiacetate-〇-hexane. The eluate was concentrated to give an oily substance (3) of 3.50 t (y, 95
h) was obtained.

MR δ 3 (ppm); Q, 76-0.92 (3H
, m), 1.12-1.56M8 (8H, m), 1.63-1.86 (3H, m),
3.72-4.20 (2H, m), 5.76-
5.96 (I H, m).

6.80-7.42 (7H, m) Other B components can also be synthesized in the same manner as in Synthesis Examples 1 and 2. Table 1 shows specific examples of component B and their physical property values.

Next, the industrial antifungal composition according to the present invention will be specifically explained using formulation examples.

Formulation Example 1 TBZ 10 parts Compound 14 phosphate 10 parts Hypophosphorous acid 35 parts Water
40 parts or more are mixed uniformly to form a suspension.

Formulation example 2 0T0 20 parts Compound 5 20 parts Propylene glycol 15 parts Water
35 parts or more are mixed uniformly to form a suspension.

Formulation Example 3 TBZ 50 parts Compound 6 50 parts or more of the two compounds are mixed uniformly.

Formulation Example 4 Compound 6 50 parts or more 2
Mix the compounds homogeneously.

Formulation Example 5 TBZ, 1 part Compound 12 1 part Propylene Glycol 5 parts 99% ethanol 83 parts Freon gas
Mix at least 10 parts uniformly to make a spray.

Next, the fungicidal effect of the composition of the present invention will be specifically explained using the following test examples.

Test Example 1 (Mold resistance test for emulsion paint) The test method was based on J-Ko S-2-2911 "Mold Resistance Test Method". That is, a predetermined concentration of the drug is added to an acrylic emulsion paint (Vini Deluxe No. 500 manufactured by Kansai Paint Co., Ltd.) and mixed well.

Apply 0.1 ml of drug-added paint to the front and back sides of a filter paper with a diameter of 3 cm.
Two coats were applied 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: -, ±.

It is shown in Table 2 in 5 levels: +, ++, +10+, and also indicates the mold resistance display method (1, 2, 3) according to the J Engineering S standard.

−, 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 about 1/6 or less of the sample surface Mold growth is observed on approximately 1/3 or more of the sample surface → Mold growth is observed on the entire sample surface unacceptable.

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

1. The area of hyphal growth observed in the area inoculated with the sample or test piece exceeds the total area τ.

Medium, water 1000 l Glucose 401 peptone 10 f agar 25 g TBZ; 2-(4-thiazolyl)-benzimidazole OTO; 2-n-octyl-4-isothiazoline-3
-Onki 1 TBZ 20 parts Lactic acid 60 parts Neugen EA-87.5 parts Water 155 parts Water 0TO20 parts Trupol AC-315310 parts Propylene glycol 15 parts Water 555 parts Water compound 5 20 parts Neugen EA-871o parts Water 700 parts Water compound No. 14 phosphate 20 parts Neugen HA-875 parts Water 75 parts Test Example 2 (Mold resistance test on ponds for direct connection to building materials) Bond for building stone sticking (with each fungicide mixed uniformly on a test agar plate)
Water kneaded materials (manufactured by Mitsui Toatsu Seibu Kenzai Co., Ltd.) were placed side by side, 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 displayed in 5 levels as in Test Example 1, and 1 and TIS standard indications (1, 2, 3) are also shown.
It is shown in Table 3.

Culture medium, water 1000m/Glucose 102 Peptone 0.52 Agar 252 Test bacteria, 7 Aspergillus niger Penicillium citrinum Rhizopus 5tolon ifer) Cladosporium herbarum (Cladosporium herbarum) Aureoba Aureojpasidium pullulan
s) Chaetomium globosum (C! haetomium globosum) Fusarium moniliforme (Table 6 I3υ); 2-benz 1 mitazole carbamate ethyl ester [Effects of the invention] As is clear from the above description, this book By using the composition of the invention, it exhibits excellent anti-fungal properties at low dosages and concentrations, where conventional commercially available drugs would not be as effective. In addition, its toxicity to humans and animals is extremely low, and at practical concentrations it does not cause skin irritation or peculiar odor, making it extremely safe to use.

For 1 year, mold has grown in the home, not only in relatively humid places such as bathrooms and closets, but also in closets.

Not only does it grow on bags and other items, ruining their aesthetic appearance, but mold! There is a strong need for ways to prevent this, as it can cause childhood bronchial asthma. Group 1 of the present invention has extremely high safety and is therefore used as a general industrial raw material.

It is extremely useful not only for this purpose, but also for mold prevention in the home.

Claims (1)

[Claims] 2-(4-thiazolyl)-benzimidazole, 2-n
At least one of -octyl-4-isothiazolin-3-one and 2-benzimidazole carbamic acid lower alkyl ester, and the general formula (I) ▲ Numerical formula, chemical formula, table, etc. ▼ (I) (In the formula, R_1 is carbon represents a straight-chain alkyl group in the range of numbers 6 to 9, R_2 and R_3 both represent a hydrogen atom, or combine to represent a methylene or alkylmethylene group), or an acid addition salt thereof. An industrial antifungal composition characterized by containing one or more types.