JPH11292719A - Industrial antiseptic and mildewproofing agent - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an industrial antiseptic and mildewproofing agent having excellent microbicidal activities against not only fungi but also bacteria and yeast by including a specific thiadiazole derivative. SOLUTION: This industrial antiseptic and mildewproofing agent contains 1,2,5-thiadiazole derivative of formula I (X is oxygen or sulfur; R1 is H or chlorine; R2 is a 1-18C alkyl), (e.g. 2-methyl-1,2,5-thiadiazol-3-one, 2-methyl-1,2,5- thiadiazole-3-thione) as an active ingredient, ordinary in an amount of 0.01-95 wt.%, preferably 0.5-70 wt.%. The compound of formula I in which X is sulfur, i.e., 2-substituted-1,2-5-thiadiazole-3-thione derivative is a new compound, and is obtained by treating 1,2,5-thiadiazol-3-one derivative of formula II with diphosphorus pentasulfide or a lawsone reagent.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

TECHNICAL FIELD The present invention relates to a compound represented by the following general formula (I) having excellent antibacterial activity against bacteria, yeasts and molds.
1,2,5-thiadiazole derivative represented by, specifically 2-
Substituted-1,2,5-thiadiazol-3-one or 2-substituted-1,2,5
The present invention relates to an industrial preservative and fungicide containing a thiadiazole-3-thione derivative as an active ingredient.

[0002]

2. Description of the Related Art As for 2-substituted-1,2,5-thiadiazol-3-one derivatives, several compounds have been known as shown below.

[0003] Journal of Organic Chemistry (J. Org. Chem.) Vol. 44, p. 1118 (1979) shows the following formula: (Wherein, R ₁ represents a hydrogen atom or a chlorine atom, and R ₂ represents a methyl group, an n-propyl group, a phenyl group, a benzyl group,
which represents an n-dodecyl group).

[0004] US Patent No. 4094986 discloses the following general formula: (Wherein, R represents an alkyl group having 1 to 16 carbon atoms, a phenyl group or a benzyl group).

JP-A-49-12034 discloses the following general formula: (Wherein R represents an alkyl group having 1 to 4 carbon atoms, and X represents a chlorine atom or a bromine atom). .

US Pat. No. 4,362,877 discloses the following general formula: Wherein R is an alkyl group having 1 to 18 carbon atoms,
A phenyl group or substituted phenyl group, R ₁
Represents an alkyl group having 1 to 18 carbon atoms, an alkoxyalkyl group, a tetrahydrofuran-2-ylmethyl group or a phenylalkyl group).

JP-A-6-305914 discloses the following general formula: (Wherein X and Y are the same or different and each represents a hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group having 1 to 4 carbon atoms, a nitro group, a trifluoromethyl group, Wherein R represents an alkoxycarbonyl group having 1 to 4 carbon atoms, and R represents an alkyl group having 1 to 6 carbon atoms).

[0008] JP-A-6-306063 discloses the following general formula: (In the formula, R represents a methyl group, a t-butyl group or a methoxy group) A wheat eye spot control agent and a medical antifungal agent containing a compound represented by the formula (I) as an active ingredient are described.

JP-A-6-306064 discloses the following general formula: Wherein X, Y and Z are the same or different;
A hydrogen atom, a halogen atom, an alkyl group having 1 to 6 carbon atoms, an alkoxy group or a nitro group having 1 to 4 carbon atoms, and R represents an alkyl group having 1 to 6 carbon atoms. A fungicide as a component is described.

[0010] Swiss Patent No. 680220 discloses the following general formula: (Wherein, R ₁ represents an alkyl group, a cycloalkyl group, a phenyl group or an alkylphenyl group, R ₂ represents a hydrogen atom,
Which shows an alkyl group, an amino group, a nitro group or an alkoxy group) as an active ingredient.

On the other hand, as shown below, only one example of a 2-substituted-1,2,5-thiadiazol-3-thione derivative is known.

Zh. Org. Khim., Vol. 29, p. 491 (199
3) has the following formula: Are described.

[0013]

SUMMARY OF THE INVENTION An object of the present invention is to provide an industrial antiseptic and fungicide having excellent bactericidal activity not only against molds but also against bacteria and yeasts.

[0014]

Means for Solving the Problems In order to achieve the above object, the present inventors have synthesized various 1,2,5-thiadiazole derivatives and made various studies. As a result, 2-substitution-1,
2,5-Thiadiazol-3-one derivatives and novel 2-substituted-
The inventors have found that 1,2,5-thiadiazole-3-thione derivatives have excellent bactericidal activity not only against molds but also against bacteria and yeasts, and have completed the present invention.

That is, according to the gist of the present invention, the following general formula (I): (Wherein X represents an oxygen atom or a sulfur atom, R ₁ represents a hydrogen atom or a chlorine atom, and R ₂ represents an alkyl group having 1 to 18 carbon atoms) 1,2,5-thiadiazole An industrial preservative and fungicide characterized by containing a derivative as an active ingredient is provided.

The 2-substituted-1,2,5-thiadiazole-3-thione derivative used in the present invention is a novel compound and has the following general formula (Ib): (Wherein, R ₁ represents a hydrogen atom or chlorine, and R ₂ represents an alkyl group having 1 to 18 carbon atoms).

Next, the compounds used in the present invention are shown in Table 1 below.
An example is shown below. The compound number is also referred to in the following description.

[0018]

Next, in the general formula (I) used in the present invention, 1,
A method for producing a 2,5-thiadiazole derivative will be described. (Wherein R ₁ or R ₂ is the same as above) That is, by treating a 1,2,5-thiadiazol-3-one derivative represented by the general formula (Ia) with diphosphorus pentasulfide or Lawesson reagent, A 1,2,5-thiadiazole-3-thione derivative represented by the general formula (Ib) can be produced.

The 1,2,5-thiadiazol-3-one derivative (Ia) which is a starting material for these reactions is a known compound,
For example, it is produced by the method described in Journal of Organic Chemistry (J. Org. Chem.), Vol. 44, p. 1118 (1979).

The industrial antiseptic / antifungal agent of the present invention containing a 1,2,5-thiadiazole derivative represented by the general formula (I) as an active ingredient is particularly useful for wood raw materials, wet pulp, paper, tatami, fibers, leather, Various industrial raw materials such as adhesives, paints, synthetic resins, and many other products that not only cause contamination due to the growth and propagation of molds, but also the deterioration of the substrate, which may impair the value as quality Or it can be applied to preservation and fungicide of industrial materials.

Here, typical molds generated in industrial raw materials include molds of the genus Penicillium, Aspergillus, Rhizopus, Ketomium, Cladosporium, Fusarium, Aureobasidium and the like. In addition, various types of fungi such as Trichoderma and wood discoloring fungi are known, but the fungi targeted in the industrial antiseptic / antifungal agent of the present invention are not limited to the above molds. . In addition, in preservation applications, it is useful for preventing damage caused by wood rot fungi and soft wood rot fungi.

The industrial preservative / antifungal agent according to the present invention comprises a carrier,
And, if necessary, in the form of a composition mixed with other auxiliaries, which are usually used as industrial preservatives and fungicides, such as oil-soluble formulations, emulsions, pastes, powders, wettable powders, and aerosols. It is used after being prepared in paints and the like.

Suitable carriers in the composition of the present invention include liquid carriers such as kerosene, ligroin, xylene, methylnaphthalene, dimethylformamide and dimethylsulfoxide or gaseous carriers such as nitrogen gas, dimethyl ether and vinyl chloride monomer. can give. Also, clay,
Inactive solid carriers such as talc, bentonite, kaolin, calcium carbonate and the like can also be used. Examples of auxiliary agents appropriately used to improve the properties of the preparation and enhance the antiseptic and antifungal effects include, for example, anionic, cationic and nonionic surfactants, methylcellulose, vinyl acetate resin, sodium alginate and the like. And the like various polymer compounds.

The above composition contains 0.01 to 95%, preferably 0.5 to 70% of the compound represented by the formula (I) as an active ingredient.
% (Weight), but the amount of the active ingredient can be appropriately changed in consideration of the type of the preparation, the type of the active ingredient compound, toxicity, the target of application, the method of application, and the like.

When using the industrial preservative / antifungal agent of the present invention, 2- (4-thiazolyl) benzimidazole (TBZ), 1,2-
Benzisothiazolin-3-one, benzyl bromoacetate, pentachlorophenol, 2,4,5,6-tetrachloro
-4-methylsulfonylpyridine, parahydroxybenzoic acid
n-butyl ester, 1,2-dibromo-2,4-dicyanobutane,
2,4,5,6-tetrachloroisophthalonitrile, parachloromethaxylenol (PCMX: trade name), 5-chloro-2-methyl-
It is possible to further improve the effect by using in combination with preservatives and fungicides such as 4-isothiazolin-3-one and 2-methyl-4-isothiazolin-3-one and wood insect repellents such as chlordane, permethrin and foxin. It is.

[0027]

Next, production examples of compounds used as active ingredients in the present invention will be shown.

Production Example 1 Production of 2-methyl-1,2,5-thiadiazol-3-one (Compound No. 1) 183 g of sulfur monochloride was dissolved in 360 ml of dimethylformamide and stirred while cooling with ice water. After adding 50 g of glycinamide hydrochloride to the resulting solution in 10 minutes, 12
Stirred for hours. The reaction mixture was poured into 1.5 liter of ice water, and the precipitated sulfur was filtered off by passing through 100 g of celite while washing with 100 ml of diethyl ether, and the resulting aqueous solution was extracted five times with 200 ml of diethyl ether. The extract was washed three times with 300 ml of saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The precipitated crystals were washed with diisopropyl ether to obtain 31 g of 3-hydroxy-1,2,5-thiadiazole (yield 70%). Then, get 3
-Hydroxy-1,2,5-thiadiazole 28 g, potassium carbonate 4
39 g of methyl iodide was gradually added dropwise to a mixed solution of 9 g and 200 ml of acetonitrile while stirring at room temperature, followed by heating at 70 ° C. for 2 hours. After completion of the reaction, the precipitated inorganic salt was separated by filtration while washing with 100 ml of acetonitrile, and the residue obtained by distilling the filtrate under reduced pressure was extracted three times with 150 ml of toluene. The extract was concentrated under reduced pressure, and the precipitated crystals were washed with diisopropyl ether to obtain 10 g (yield 30%) of the title compound. [Melting point: 114-115 [deg.] C., mass spec: m / e 116 (M ^<+> )].

Production Example 2 Production of 2 -methyl-1,2,5-thiadiazole-3-thione (Compound No. 2) 2-Methyl-1,2,5-thiadiazole-3- obtained in Production Example 1
2.5 g of ON was dissolved in 25 ml of toluene. 5 g of diphosphorus pentasulfide was added to the resulting solution at room temperature, and the mixture was stirred at 80 ° C. for 40 minutes. The supernatant was filtered off, and the residue was extracted three times with 30 ml of hot toluene. The extract was washed with saturated saline, dried over anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The obtained crystals were recrystallized from methanol to give the title compound (1.4 g, yield 50%).
I got [Melting point 105-106 ° C, mass spec.m / e 132
(M ⁺ )].

Production Example 3 Preparation of 2-methyl-4-chloro-1,2,5-thiadiazole-3-thione (Compound No. 4) 2-Methyl-4-chloro-1,2,5-thiadiazole-3 1.5 g of -one (Compound No. 3) was dissolved in 50 ml of toluene. The resulting solution was added to Lawesson's reagent [2,4-bis (4-methoxyphenyl) -1,3-
Dithia-2,4-diphosphetane-2,4-disulfide] 2.2 g
Was added and stirred at 100 ° C. for 30 minutes. After evaporating the solvent, 0.8 g of the title compound was purified by silica gel chromatography (eluent: toluene / acetone 100: 1).
(47% yield). [Melting point 96-99 ° C, mass spec.m / e
166 (M ⁺ )].

Production Example 4 Production of 2-n-octyl-1,2,5-thiadiazole-3-thione (Compound No. 20) 2-n-octyl-1,2,5-thiadiazole-3-one (compound No. 20) No.
20) 1.5 g was dissolved in 30 ml of xylene. 1.5 g of diphosphorus pentasulfide was added to the obtained solution, followed by stirring at 80 ° C. for 2 hours. The supernatant was filtered off, the residue was extracted three times with 30 ml of xylene, the extract was washed twice with 30 ml of saturated saline, dried over anhydrous sodium sulfate, the solvent was distilled off, and the residue was subjected to silica gel chromatography (elution). (Agent: toluene) to give 0.6 g (yield 38%) of the title compound. [Melting point 28-30 [deg.] C., mass spectrometry value: m / e 230 (M ^<+> )].

Production Example 5 2-n-octyl-4-chloro-1,2,
Preparation of 5-thiadiazole-3-thione (Compound No. 22) 2-n-octyl-4-chloro-1,2,5-thiadiazole-3-one
(Compound No. 22) 2 g was dissolved in toluene 20 ml. 2 g of diphosphorus pentasulfide was added to the resulting solution, and the mixture was stirred at 80 ° C. for 2 hours. The residue obtained by the same treatment as in Example 4 was purified by silica gel chromatography (eluent: n-hexane / acetone 20: 1) to give 1.3 g of the title compound.
(62% yield). [Melting point 25-27 ° C, mass spectrometry value: m / e
264 (M ⁺ )].

Next, some formulation examples of the industrial antiseptic / antifungal agent of the present invention will be given, but it goes without saying that the amount of the antiseptic and the fungicide can be varied. Also, compounds
A formulation can be similarly prepared by replacing No. 1 with compounds No. 2 to No. 24. All parts in the preparation examples are parts by weight.

Formulation Example 1 Emulsion 10 parts of Compound No. 1 is dissolved in 40 parts of dimethylformamide, and 50 parts of xylene and 10 parts of polyoxyethylene nonylphenyl ether are added to this solution and mixed well to obtain an emulsion. Was.

Formulation Example 2 Powder 2 parts of Compound No. 2 were dissolved in 10 parts of acetone, and 68 parts of clay and 30 parts of talc were added to the solution and mixed uniformly. Thereafter, acetone was evaporated off to obtain a powder.

Formulation Example 3 Water dispersible compound 40 parts of compound No. 1, 56 parts of clay, 3 parts of sodium lauryl alcohol sulfonate and 1 part of polyvinyl alcohol are uniformly mixed in a mixer and ground by a hammer mill. A wettable powder was obtained.

Formulation Example 4 Oil-soluble agent 2 parts of Compound No. 2 was dissolved in 2 parts of dimethylformamide, and 96 parts of solvent naphtha was added to obtain an oil.

Formulation Example 5 2 parts of aerosol compound No. 4 and 0.5 part of fragrance were added to deodorized kerosene 40
And dissolved in an aerosol container. After mounting the valve, 58 parts of liquefied petroleum gas was charged under pressure to obtain an aerosol.

Formulation Example 6 20 parts of flowable compound No. 20, compound lauryl sulfate 2
Parts, 0.2 parts of xanthan gum and 77.8 parts of water were put in a ball mill and pulverized and mixed for 12 hours to obtain a flowable agent.

Next, the effects of the antiseptic / antifungal agent of the present invention will be described with reference to test examples. Test Example 1 Measurement of Antiseptic and Antifungal Activity (Measurement of MIC) Various bacteria of the compound represented by the general formula (I) used as an active ingredient in the industrial antiseptic and antifungal agent of the present invention by an agar medium dilution method. Minimum inhibitory concentration (MIC) (pp
m unit) was measured. The culture medium is a mold consisting of mold, yeast, yeast 200 g, glucose 20 g, meat extract 5 g, and agar 20 g when yeast is used.If the test bacteria is bacteria, meat extract 5 g, peptone 10 g, salt 5 g and A medium consisting of 15 g of agar was used. Incubate at 28 ° C for 96 hours if the test bacterium is a mold or yeast; 37 ° C if the test bacterium is a bacterium
For 24 hours. The test concentration (ppm) of the test compound is 100,
The test was performed in eight stages of 50, 25, 12.5, 6.3, 3.2, 1.6 and 0.8. The MIC was indicated by inoculating a test bacterium on a medium having the test concentration described above, and determining the MIC value as the minimum concentration at which the bacterium did not grow after culturing.

[0041] As the test bacteria, fungi Aspergillus niger S1 (Aspergillus niger S1) [abbreviation ANS1], Aspergillus niger S2 (Aspergillus niger S2), Aspergillus terreus (Aspergillus terreus S3), Penicillium
Citrinum ( Penicillium citrinum S5) [Pb], Penicillium funiculosum S6, Cladosporium Cladosporium c
ladosporioides S8) [abbreviation Cc], Aureobasidium pullulans S9, Gliocladium virens S10, Fusarium proliferatum S12 [abbreviation Fp], Myrothecium verrucaium
ria S13) and Alternaria citr
i ) Ten kinds of [abbreviation Ac] were used.

Bacteria are Bacill subtilis ( Bacill).
us subtilis ATCC 6633) [Abbreviation Bs], Bacillus cereus
( Bacillus cereus ), Escherichia c
oli IFO 3301) [abbreviation Ec], Enterobacter aerogenes (Enterobacter aerogenes IAM 1063), Pseudomonas aeruginosa (Pseudomonas aeruginosa) [abbreviation Pa], Staphylococcus aureus (Staphylococcus aureus
IFO 12732) [abbreviation Sa] and Klebziella nimononiae ( Kl
ebsiella pneumoniae IAM 4942 ). In addition, yeast is Candida albican
s ), Rhodotorula minuta , Rhodotorula mucilagi nosa , Rhodotorula texensis and Saccharomyces cerevisiae
IAM 494) [Abbreviation Sc] was used.

Compounds No. 1, No. 3, No. 4, No. 19 and No. 21 exemplified in Table 1 were tested as test compounds. Table 2 shows the results.

[0044]

Test Example 2 Measurement of Preservative and Fungicide Activity (Measurement of Inhibition Circle on Medium) The above test was carried out by a usual paper disk method.
That is, a paper disk having a diameter of 8 mm is immersed in a water or acetone solution (concentration: 1000 μg / ml) of a 1,2,5-thiadiazole derivative represented by the general formula (I),
Used after drying. The abbreviations and culture media of the test bacteria used are as shown in Test Example 1. The antiseptic and antifungal activity was measured by measuring the diameter of a growth inhibition circle formed around the paper disk. Table 3 shows the obtained results. In addition, the display which shows the said activity is as follows. A: The diameter of the growth inhibition circle is 40 mm or more B: The diameter of the growth inhibition circle is 20 mm or more and less than 40 mm C: The diameter of the growth inhibition circle is 9 mm or more and less than 20 mm D: No growth inhibition circle is observed.

[0046]

Test Example 3 Test for preservative effect of casein 10 parts of casein, 88 parts of an aqueous solution containing an emulsion prepared according to Formulation Example 1 at a predetermined concentration, and 2 parts of aqueous ammonia
Part into a 200 ml flask and stir at 80 ° C
Then, a casein solution is prepared while gradually cooling. Put it in a 200 ml beaker, and add 0.1 ml of the degraded casein (10 ⁸ viable cells / ml). Cover the beaker with aluminum foil and incubate in a thermostat at 30 ° C. After 10 days and 20 days, 1 ml of the casein solution was taken out, and the number of viable bacteria in 1 ml was measured by an agar plate dilution method. Table 4 shows the obtained results.

[0048]

Test Example 4 Mold Resistance Test of Emulsion Paint The test method was performed according to JIS Z 2911. That is, a flowable agent prepared according to Formulation Example 6 is added to a vinyl acetate emulsion white paint so as to have a predetermined concentration, and the mixture is stirred and mixed with a homogenizer for 30 seconds to prepare a paint. A filter paper (Toyo Filter Paper No. 2) having a diameter of 12.5 cm is immersed in the obtained coating liquid to uniformly disperse the sample, and air-dried at room temperature for 48 hours. In this case, the thickness of the coating film is uniform, and the weight of the paint adhered to the filter paper is 90 to 11 times the weight of the paper.
Adjust to be 0%. This filter paper was used as a circular test piece having a diameter of 3 cm, and one beaker having a capacity of 200 ml was prepared for each test piece.
Immersed the test piece for 18 hours, took out the test piece, hung it at room temperature for 2 hours, and further dried it (80-85
℃). Two hours later, the test piece was taken out, attached to the center of the culture surface of the agar medium (composition: glucose 40 g, peptone 10 g, agar 25 g and purified water 1000 ml) in a Petri dish, and then Aspergillus niger, Penicillium funiculosum, Cladosporium cladosporio. Ides,
A mixed spore suspension of Gliocladium virens and Aureobasidium pullulans is evenly spray inoculated on the medium surface and the test piece. The petri dish was covered and cultured in a thermostat at 28 ± 2 ° C. After 3 days, 7 days and 14 days, the growth condition of the mold on the test piece was examined according to the following criteria.
Table 5 shows the obtained results.

Investigation criteria 3 No hyphal growth was observed in the inoculated portion of the test piece or sample. 2. The area of the hyphal growth area visually observed in the sample piece or the inoculated portion of the sample does not exceed 1/3 of the total area. (1) The area of the hyphal growth area visually observed in the sample piece or the inoculated portion of the sample exceeds 1/3 of the total area.

[0051]

[0052]

Industrial Applicability The industrial antiseptic / antifungal agent of the present invention has a high bactericidal effect against fungi, bacteria and yeast, and can be widely used as an industrial antiseptic / antifungal agent.

 ──────────────────────────────────────────────────続 き Continued on the front page (72) Inventor Kiyoshi Hirasawa 3-8 Morinosato, Atsugi City, Kanagawa Prefecture 2-305 Central View Heights (72) Inventor Seiichi Kutsuma 1-5-9-901 Tsumada Higashi, Atsugi City, Kanagawa Prefecture

Claims (2)

[Claims] 1. The following general formula (I): (Wherein X represents an oxygen atom or a sulfur atom, R ₁ represents a hydrogen atom or a chlorine atom, and R ₂ represents an alkyl group having 1 to 18 carbon atoms) 1,2,5-thiadiazole An industrial preservative / antifungal agent comprising a derivative as an active ingredient. 2. An industrial preservative / antifungal agent comprising, as an active ingredient, a 1,2,5-thiadiazole derivative in which X in the general formula (I) according to claim 1 is a sulfur atom.