JP2704467B2 - Industrial antibacterial agent that has both bactericidal and inhibitory power - Google Patents

Description

DETAILED DESCRIPTION OF THE INVENTION

The present invention relates to an inhibitor for slime generated in papermaking process water or industrial water in the pulp and paper industry, or as a preservative for starch paste, wood, leather, metalworking oils, paints and adhesives. A useful industrial antibacterial agent.

[0002]

2. Description of the Related Art The growth of microorganisms in industrial water causes a decrease in quality of products using the same and a decrease in productivity of product production. The control of microorganisms, especially in recirculating water systems,
It is a very important factor in industrial production.

[0003] That is, in a pulp and paper mill, when slime produced by the growth of bacteria and fungi is generated in the papermaking process water (white water), the sludge falling from the apparatus lowers the paper quality or causes high-speed machines. This causes the serious problem of running out of paper in the papermaking process. Similarly, in a typical factory recirculating cooling water system, slime and algae also close the cooling tower or attach to the heat exchanger, significantly reducing its capacity. In particular, starch paste liquid used as a surface sizing agent in the pulp and paper industry is extremely susceptible to spoilage due to high nutrition. In addition, metalworking oils, paints, adhesives, wood, leather, and the like are also prone to rot and mold.

Conventionally, mercury agents such as mercury ethyl phosphate and mercury phenyl phosphate and tin agents such as tributyltin oxide have been used to protect against damage caused by the generation and growth of such microorganisms. Is extremely toxic and its use has been regulated due to environmental pollution. Organic chlorinating agents such as trichlorophenol and pentachlorophenol, as well as organic sulfur agents and quaternary ammonium salts, have been used as substitutes for these, but have had many problems due to odor, color tone and foaming.

[0005] Commercially available industrial antibacterial agents include
A bactericide (2,2-dibromo-2-cyanoacetamide, etc.) which makes a drug sterilize at once by contacting it with a bacterium, and has a small ability to kill the bacterium even when the drug is brought into contact with the bacterium. Are inhibitors (3-isothiazolones, benzoisothiazolones, 2-
Bromo-2-nitro-1,3-propanediol, methylene dithiocyanate, etc.). However, some applications require agents that have both bactericidal and inhibitory powers. In other words, in a system where bacteria are growing,
This is a fungicide utilizing a mechanism in which the number of viable bacteria is reduced by adding a fungicide, and then an inhibitor is added to suppress the growth of living bacteria over a long period of time.

[0006] In order to realize this, conventionally, it has been achieved by blending a bactericide and an inhibitor in an appropriate ratio and adding this blended drug.

[0007] However, the compounding agent may have difficulty in compounding or manufacturing, or may have an antagonistic effect in which the compounding agents react with each other to decompose or coagulate, or conversely, the antibacterial activity is reduced. Furthermore, antibacterial agents generally have a property of being easily decomposed, such as hydrolysis or thermal decomposition, so that there is a problem that the life of the compounding agent is limited by the life of the shorter drug.

[0008]

DISCLOSURE OF THE INVENTION The present inventors have invented dichloroglyoxime as a novel slime control agent which can be substituted for a conventional fungicide and which works effectively at a low concentration from the viewpoint of environmental pollution. No. Hei 3-21385). However, this drug has a drawback that it has a strong bactericidal activity but has a small inhibitory power. The inventor of the present invention required an inhibitory force for suppressing the growth of bacteria for a long period of time depending on the application, and further studied the agent having both a strong bactericidal effect and an inhibitory effect. SUMMARY OF THE INVENTION An object of the present invention is to provide a novel industrial antibacterial agent having both strong bactericidal and inhibitory activities.

[0009]

DISCLOSURE OF THE INVENTION The present inventors have found that an ester of a glyoxime halide represented by the formula 1 has a strong inhibitory force while maintaining a strong bactericidal activity. That is, the gist of the present invention is represented by Formula 1:

[0010]

Embedded image

(In the formula 1, X is halogen, and Y is the same or different halogen atom or hydrogen atom as X;
R ¹ and R ² represent formyl, alkyl (C = 1 to 18) carbonyl, haloalkylcarbonyl, alkenylcarbonyl, haloalkenylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, alkoxycarbonylcarbonyl, alkoxycarbonylalkylcarbonyl, cycloalkylcarbonyl, Arylcarbonyl substituted or substituted with one or more halogen, nitro group, cyano group, aryloxycarbonyl unsubstituted or substituted with one or more halogen, nitro group, cyano group,
Arylalkylcarbonyl, alkylaminocarbonyl, unsubstituted or substituted by one or more halogen, nitro group, cyano group, arylaminocarbonyl unsubstituted or substituted by one or more halogen, nitro group, cyano group, 1 A carbonyl group selected from the group consisting of a 5- or 6-membered heterocyclic carbonyl containing a heteroatom as described above,
R ¹ and R ² are the same or different carbonyl groups, or one of R ¹ and R ² is the above-mentioned carbonyl group and the other is a hydrogen atom). An industrial antibacterial agent comprising a mono- or diester as an active ingredient.

In the above formula 1, for example, X = Y, R ¹
= R ² , X and Y between C and C, or N = O
R ¹ and N = OR ² can take the cis, trans form, and the two oximes can both take the anti, amphi, syn form (Cher
ska, N .; O. et al, Izv. Akad. Nauk SSSR, Serk
him. , (10) 2348-51 (1986); CA1.
07: 133624). Thus, there are a total of six stereoisomers, each of which, or a mixture thereof, is encompassed by the present invention. Further, in Expression 1, X ≠
In the case of Y, R ¹ ≠ R ² , various isomers can be taken, all of which are included in the present invention.

As typical compounds of the industrial fungicide according to the present invention, there can be mentioned, for example, the compounds shown in Table 1, but the present invention is not limited to these compounds.

[0014]

[Table 1]

The industrial bactericide according to the present invention is used as a powder as it is or as a suspension or solution depending on the use. Generally, esters of glyoxime halides are hardly soluble in water and are often used as an aqueous suspension in the form of fine particles. In this case, a surfactant may be used as a dispersant, and the emulsion may be used as an emulsion. When used as a solution or suspension, examples of the organic solvent used include alcohols, polyhydric alcohols, ethers, ketones, carboxylic acids, esters, amides, nitriles, and sulfoxides. For example, glycols such as methanol, ethanol, propanol, 2-propanol, butanol, ethylene glycol, diethylene glycol, and propylene glycol, and mono- or diethers of the glycols such as methyl and ethyl, acetic acid, ethyl acetate, butyl acetate, N, N '-Dimethylformamide, N, N'-dimethylacetamide, acetonitrile, dimethylsulfoxide and the like.

Next, a few examples of preparations will be shown. Preparation Example 1, dichloroglyoxime diacetate (1) 3 g N, N'-dimethylformamide 95 g surfactant (Tetronic TR-702, manufactured by Asahi Denka Kogyo Co., Ltd.) 2 g Preparation Example 2, dichloroglyoxime dihexanoate ( 3) 5 g N, N'-dimethylformamide 93 g Surfactant (Tetronic TR-702, manufactured by Asahi Denka Kogyo KK) 2 g Formulation Example 3, bis (N-methylcarbamic acid) dichloroglyoxime (7) 5 g N , N'-dimethylformamide 93 g Surfactant (Tetronic TR-702, manufactured by Asahi Denka Kogyo KK) 2 g

Next, as reference examples, synthetic examples of glyoxime, monochloroglyoxime and dichloroglyoxime, which are raw materials of the industrial bactericide according to the present invention, will be described. It was synthesized with reference to Reference Example 1, glyoxime US 4,539,405. In a 1 liter four-necked flask, add hydroxylamine hydrochloride 139
g (2 mol) and 100 ml of water are added and dissolved by stirring.
Then, after adding 145 g (1 mol) of 40% glyoxal, the mixture is cooled to 5 ° C. in an ice water bath. 106 g (1 mol) of powdered sodium carbonate (anhydrous) was added little by little over 1 hour. The ice-water bath was removed, and the mixture was stirred overnight at room temperature, and then heated and refluxed for 1 hour and 30 minutes on an oil bath. After cooling with ice water to 0 ° C., suction filtration, washing with cold water and drying, 72.4 g of light brown crude glyoxime (82.2 g) was obtained.
%). mp 147 ° C (dec), ir = 317
6,2880 ¹ H NMR (CDCl ₃ + DMSO-d ₆ )
δ7.73 s, δ10.77 broad This was used as a raw material for the next step chlorination.

Reference Example 2, dichloroglyoxime (A) US Pat. No. 4,539,405. In a 1-liter four-necked flask, 35.2 g of crude glyoxime (0.
4mol) and 400 ml of 99.5% ethanol were stirred and dissolved. The reaction mixture was cooled to −20 ° C. in a dry ice-methanol bath, and 70 g of chlorine (0.
987 mol) was blown in over 20 minutes. After aging at 0 ° C. for 1 hour and at room temperature for 1 hour, ethanol was distilled off under reduced pressure.
120 ml of chloroform was added to the residue for dispersion. After suction filtration and vacuum drying, 44.5 g of white crystals were obtained. mp
201-204 ° C, ir (cm ^-1 ) = 3270,162
2,1414 ¹ H NMR (CDCl ₃ + DMSO-
d ₆ ) δ 12.38 s,

Reference Example 3, Monochloroglyoxime
(B) Monochloroglyoxime, which is present as an intermediate for the synthesis of dichloroglyoxime in Reference Example 2 and is recognized as a possible impurity of dichloroglyoxime, was prepared according to J. Am. Org. Che
m. , 48, 366-372, 1983. 49.7 g (0.30 mol) of chloral hydrate and 32.9 g (0.45 mol) of hydroxylamine hydrochloride
To a reaction mixture of water and 100 ml of water, 90 g of a 20% aqueous sodium hydroxide solution was added dropwise at 10 ° C. or lower on an ice bath. After stirring and aging for 4 hours at room temperature, the mixture was ice-cooled again, and 150 g of a 32% aqueous sodium hydroxide solution was added dropwise. After 5 minutes, 25% sulfuric acid 26
4 g were added dropwise. The precipitated crystals were filtered by suction and dried. The crystals were extracted with 500 ml of tetrahydrofuran and concentrated. Hexane was added to the residue, which was crystallized, filtered and dried. 13.3 g (36.2%) of white crystals were obtained. m
p150 ° C. (dec), ir (cm ⁻¹ ) = 3260 (wide), 1624, 1454 ¹ HNMR (DMSO-d ₆ )
δ 8.36 s, δ 12.21 d J = 6.8H
z,

[0020]

EXAMPLES Examples of the present invention will be shown and described more specifically. Example 1, dichloroglyoxime diacetate (1) 10.0 g (63.6 mmol) of dichloroglyoxime
Is dissolved in 20 ml of tetrahydrofuran, and acetic anhydride 1 is dissolved.
After adding 3.8 g (135 mmol) and 0.2 ml of pyridine and stirring at room temperature for 3 hours, the reaction solution was dispersed in ice water,
After extraction with chloroform, drying over anhydrous magnesium sulfate and concentration under reduced pressure, 10.6 g of crude crystals were obtained. Reconstitute with chloroform-hexane to obtain 8.9 g of white crystals.
(57.8%) were obtained. mp 158-160 ° C, i
r = 1818 cm ^-1 , ¹ H NMR (CDCl ₃ ) δ 2.3
1 s,

Example 2, dichloroglyoxime dibenzoate (2) 8.0 g (50.9 mmol) of dichloroglyoxime and 23.3 g (103 mmol) of benzoic anhydride were dissolved in 30 ml of tetrahydrofuran, and 0.2 ml of pyridine was added. Stirred at room temperature for 16 hours. The precipitated crystals are collected by filtration,
After washing with hot chloroform and reconsolidation with DMF,
9.6 g (51.6%) of white crystals were obtained. mp21
6-218 ° C., ir = 1768 cm ⁻¹ , ¹ H NMR (C
DCl ₃ ) δ 6.82 s

Example 3, dichloroglyoxime dihexanoate (3) 7.0 g (44.5 mmol) of dichloroglyoxime and 21.0 g (98 mmol) of hexanoic anhydride were dissolved in 30 ml of tetrahydrofuran, and 0.2 ml of pyridine was added. The mixture was stirred at 40 ° C for 7 hours. The reaction solution was dispersed in ice water, extracted with chloroform containing a small amount of ethyl acetate,
It was concentrated under reduced pressure. This was reconstituted with hexane to give white crystals 1
0.3 g (65.3%) was obtained. mp57-59
° C, ir = 1802 cm ^-1 ,

Example 4, bis (cyclohexanecarboxylic acid) dichloroglyoxime (4) 4.0 g (25.0 mmol) of dichloroglyoxime was dissolved in 20 ml of methyl ethyl ketone, and 8.0 g (54.5 mmol) of cyclohexanecarbonyl chloride and pyridine 3 were dissolved. After adding 0.9 ml and stirring and refluxing for 4 hours, the reaction solution was dispersed in ice water-dilute hydrochloric acid, extracted with chloroform, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure to obtain 9.3 g of crude crystals. After re-consolidation with chloroform-ethanol, 4.0 g (26.8%) of white needle crystals were obtained. mp 138-141 ° C., ir = 1796 cm ⁻¹ ,

Example 5, bis (chloroacetic acid) dichloroglyoxime (5) 7.85 g (50.0 mmol) of dichloroglyoxime
And bis (chloroacetic acid) anhydride 21.4 g (125 mmol
l) was dissolved in 30 ml of tetrahydrofuran, 0.2 ml of pyridine was added, and the mixture was stirred at room temperature for 2 hours. The precipitated crystals were separated by filtration, the filtrate was concentrated to half the volume, cooled, crystallized and collected. This was repeated twice to obtain 10.8 g of crude crystals. This was reconstituted with ethylene glycol dimethyl ether / water to obtain 9.7 g (62.5%) of white crystals. mp15
6-158 ° C., ir = 1800 cm ⁻¹ , ¹ H NMR (D
MSO-d ₆₎ δ4.06s

Example 6, bis (trichloroacetic acid) dichloroglyoxime (6) 4.0 g (25.4 mmol) of dichloroglyoxime was dissolved in 15 ml of a benzene-DMF mixed solvent, and 9.5 g (52.2 mmol) of trichloroacetyl chloride was dissolved. A solution of benzene and 15 ml of benzene was added dropwise under ice cooling. 40-50 ° C
After stirring and aging for 1 hour, the mixture was filtered to obtain 6.9 g of crude crystals. 2
-1.8 g (26.0%) of white crystals reconstituted with butanone
I got mp 158.5-160.5 ° C, ir = 180
2cm ^-1

Example 7 Bis (N-methylcarbamic acid) dichloroglyoxime (7) The compound was synthesized with reference to GB1307223. 7.5 g (47.7 mmol) of dichloroglyoxime was dissolved in 20 ml of tetrahydrofuran, 30 ml of methyl isocyanate and 0.4 ml of pyridine were added, and the mixture was stirred with heating. The precipitated crystals were collected by filtration to obtain 4.8 g. This is reconstituted with methanol,
2.88 g (22.2%) of white crystals were obtained. mp191
-193 (dec), ir = 1756 cm ^-1 , ¹ HNM
R (DMSO-d ₆ ) δ 2.73 d (J = 4.6H)
z), δ 7.96 d (J = 4.6 Hz)

Example 8, dichloroglyoxime diisonicotinate dihydrochloride (8) 4.0 g (25.5 mmol) of dichloroglyoxime
Was added with 2 ml of benzene, then dissolved in 20 ml of DMF, and 10.0 g of isonicotinic acid chloride hydrochloride (5 g) was added.
6.2 mmol) and 10 ml of DMF were added, and the mixture was heated with stirring at a bath temperature of 50-60 ° C for 1 hour. The precipitated crystals were collected by filtration to obtain 12.1 g of crude crystals. When this was reconstituted from N, N-dimethylformamide / water, pale brown crystals were obtained in 0.1%.
5 g (4.5%) were obtained. mp 231 ° C (dec),
ir = 1790 cm ^-1

Example 9, di (2-furic acid) dichloroglyoxime (9) 6.2 g (39.5 mmol) of dichloroglyoxime was dissolved in 25 ml of 2-butanone, and 11.4 g of 2-furoyl chloride (87. After adding 3 mmol), 2.7 ml of pyridine was gradually added dropwise, followed by stirring at room temperature for 2 hours. The precipitated crystals were collected by filtration and dried to obtain 12.4 g of crude crystals. This was recombined with N, N-dimethylformamide to obtain 2.5 g (18.3%) of white crystals. ir = 17
62 cm ^-1 , mp 231-233 ° C (dec)

Example 10 Bis (N-phenylcarbamic acid) dichloroglyoxime (10) 7.5 g (47.7 mmol) of dichloroglyoxime was dissolved in 20 ml of tetrahydrofuran, and phenylisocyanate was dissolved in 12 ml.
After adding 6 g (105 mmol), pyridine 0.5m
and stirred at 60-70 ° C for 2 hours. The reaction solution was cooled, and pale red precipitated crystals were collected by filtration and dried to obtain 5.2 g.
I got This was reconstituted with methanol containing a small amount of 2-butanone to obtain 3.2 g (16.9%) of white crystals.
mp180-181 ° C (dec), ir = 1758cm
^{¯ 1, 1 HNMR (DMSO-} d 6) δ7.0-7.6
m, 10.3s

Example 11, bis (tert-butoxycarboxylic acid) dichloroglyoxime (11) 1.57 g (10.0 mmol) of dichloroglyoxime
Was dissolved in 5 ml of tetrahydrofuran, 5.33 g (24.4 mmol) of di-tert-butyl dicarboxylate was added, and then a catalyst amount of pyridine was added, followed by stirring at room temperature for 15 hours. The precipitated crystals were collected by filtration and dried to obtain 2.6 g.
This was reconstituted with a hexane-benzene mixed solvent to obtain 2.25 g (63.0%) of white crystals. mp112-11
4 ° C. (dec), ir = 1800 cm ⁻¹

Example 12 Monochloroglyoxime diacetate (12) 1.23 g of monochloroglyoxime (10.0 mmol)
l) was dissolved in 10 ml of tetrahydrofuran, 2.25 g (22.0 mmol) of acetic anhydride was added, and then a pyridine catalyst amount was added, followed by stirring at room temperature for 3 hours. The reaction solution was concentrated under reduced pressure, reconstituted with THF and hexane, and 1.7 g of a white crystal was obtained.
(82.1%). mp114-117, ir = 1
762 cm ^-1 , ¹ H NMR (CDCl ₃ ) δ 2.28 s
6H, δ8.65 s 1H

Example 13 Monochloroglyoxime dibenzoate (13) 1.23 g of monochloroglyoxime (10.0 mmol)
l) was dissolved in 10 ml of tetrahydrofuran, 3.09 g (22.0 mmol) of benzoic anhydride was added, and then a pyridine catalyst amount was added, followed by stirring at room temperature for 15 hours. The reaction solution was concentrated under reduced pressure, reconstituted with methanol, and 1.0 g of a white crystal was obtained.
(15.8%). mp154-157 ° C ir =
1760 cm ^-1 , ¹ H NMR (CDCl ₃ ) δ 7.4
7.7 m 6H, δ 7.9-8.2 m 4H, δ
8.8 s 1H

Example 14, di (2-thenoic acid) dichloroglyoxime (14) 4.7 g (30 mmol) of dichloroglyoxime was dissolved in 25 ml of methyl ethyl ketone, and 9.24 g of 2-thenoyl chloride (2-thiophenecarbonyl chloride) was dissolved. 6
After adding 3 mmol), 2.37 g of pyridine (30 m
mol) was added dropwise and stirred at 40 ° C. for 2 hours. The precipitated crystals were collected by filtration and recrystallized from DMF to obtain 3.86 g (34.1%) of white crystals. mp215.5-2
18.5 ° C. ir (KBr) = 1760 cm ⁻¹

Example 15 Bis {N- (4-chlorophenyl) carbamic acid} dichloroglyoxime (15) 1.57 g (10 mmol) of dichloroglyoxime was dissolved in 10 ml of methyl ethyl ketone, and 4-isocyanic acid was added.
After adding a solution of 3.38 g (22 mmol) of chlorophenyl in 10 ml of methyl ethyl ketone, the solution was added at 40 ° C.
, And the mixture was stirred at the same temperature for 2 hours. The precipitated crystals were collected by filtration and recrystallized from diethyl ketone to obtain 3.87 g (83.4%) of white crystals. mp200.5-202.5 ° C ir (KBr) =
3408, 1798, 1598, 1522, 1176,
990cm ^-1

Example 16, dichloroglyoxime dinicotinate hydrochloride (16) 7.12 g of nicotinoyl chloride hydrochloride (40 mmol)
1) was dissolved in 20 ml of DMF, and a solution of 3.14 g (20 mmol) of dichloroglyoxime and 20 ml of methyl ethyl ketone was added dropwise under ice-cooling to precipitate crystals. After stirring at room temperature for 6 hours, the crystals were collected by filtration and recrystallized from DMF to obtain 6.0 g (68.1%) of pale yellowish white crystals. mp161
° C (dec) ir (KBr) = 1768 cm ^-1

Example 17 bis {4-methylthiazol-5-carboxylic acid} dichloroglyoxime dihydrochloride (1
7) 7.11 g (44 mmol) of 4-methylthiazol-5-carbonyl chloride hydrochloride was dissolved in 18 ml of DMF, and 3.14 g (20 mm) of dichloroglyoxime was cooled under ice-cooling.
ol) and 12 ml of methyl ethyl ketone,
When a catalytic amount of triethylamine was added, crystals gradually precipitated. After stirring at room temperature overnight, the crystals were collected by filtration and recrystallized from DMF to obtain 3.7 g (38.5%) of white crystals. m
p267-269 ° C (dec) ir (KBr) = 17
70cm ^-1

The germicidal and disinfecting powers of the industrial germicides according to the present invention obtained in the above Examples were tested. Test Example 1, Bacterial Bactericidal Test The test bacteria were Esch as a representative gram-negative strain.
erichia coli JMC1649 (E.co.
li) and Buci as a representative gram-positive strain
llus subtilis JCM1465 (B.s
ub) is suspended in physiological saline so that the number of bacteria is about 10 ⁶ / ml. Compound Nos. (1) to (13) of the present invention and Comparative Products (A) to (F) are added to each of these to give respective concentrations, and shaking culture is performed at 30 ° C. for 1 hour. The number of surviving bacteria after the cultivation is measured according to a conventional method, and the concentration at which 99.9% or more of the control bacteria has been killed is defined as the bactericidal concentration. Table 2 shows the results.

[0038]

[Table 2]

Comparative compound name C: methylene dithiocyanate D: 2-bromo-2-nitro-1,3-propanediol E: 5-chloro-2-methyl-3-isothiazolone / 2
-Methyl-3-isothiazolone (9: 1) composition F: 2,2-dibromo-2-cyanoacetamide

Test Example 2 Bacterial Suppression Test The test bacteria were Esch as a representative gram-negative strain.
erichia coli JMC1649 (E.co.
li) and Buci as a representative gram-positive strain
llus subtilis JCM1465 (B.s
ub) is suspended in physiological saline so that the number of bacteria is about 10 ⁶ / ml. Compound Nos. (1) to (13) of the present invention and Comparative Products (A) to (F) were added to each to each concentration, followed by shaking culture at 30 ° C. for 24 hours, and growth of the bacteria was observed. The concentration that could not be obtained was taken as the effective concentration. Table 3 shows the results.

[0041]

[Table 3]

Comparative compound name C: methylene dithiocyanate D: 2-bromo-2-nitro-1,3-propanediol E: 5-chloro-2-methyl-3-isothiazolone / 2
-Methyl-3-isothiazolone (9: 1) composition F: 2,2-dibromo-2-cyanoacetamide

Test Example 3, Mold inhibition test Aspergillus niger was used as a test strain.
var intermedius JCM1863
(Abbreviated Asp.niger) and Cladosporiu
m cladosporioides JCM6021
(Abbreviated Clad. Clad) was used. About 10 ³ spores / m 2 in potato dextrose medium (Difos)
of the present invention, and Compound Nos. (1) to (13) of the present invention and Comparative Products (A) to (F) were added to each concentration. Shaking culture was performed at 25 ° C. for 5 days, and the concentration at which no hyphal growth was observed was defined as the effective concentration. Table 4 shows the results
Shown in

[0044]

[Table 4]

Comparative compound name: C: methylene dithiocyanate D: 2-bromo-2-nitro-1,3-propanediol E: 5-chloro-2-methyl-3-isothiazolone / 2
-Methyl-3-isothiazolone (9: 1) composition F: 2,2-dibromo-2-cyanoacetamide

Test Example 4 Yeast Suppression Test Rhodolorula lacto was used as a test strain.
sa JCM1546 (Rhodo. lacto) was used. Yeast was suspended in a glucose peptone medium (manufactured by Nissui Co., Ltd.) at a concentration of about 10 ⁴ cells / ml, and compound numbers (1) to (13) of the present invention and comparative products (A) to (F) were prepared. It was added to each concentration. Shaking culture was performed at 25 ° C. for 5 days, and the concentration at which no yeast growth was observed was defined as the effective concentration. Table 5 shows the results.

[0047]

[Table 5]

Comparative compound name C: methylene dithiocyanate D: 2-bromo-2-nitro-1,3-propanediol E: 5-chloro-2-methyl-3-isothiazolone / 2
-Methyl-3-isothiazolone (9: 1) composition F: 2,2-dibromo-2-cyanoacetamide

Test Example 5, Test for suppression of white water in papermaking process 5 parts by weight of white water sampled from a coated base paper machine at a certain paper mill were mixed with 4 parts by weight of a modified Waxman's medium, and 9 ml was placed in an L-shaped culture tube. After dispensing, compound Nos. (1) to (13) of the present invention and comparative products (A) to (F) were added to each concentration, and cultured with shaking at 30 ° C. for 24 hours to grow cells. The concentration at which no was observed was defined as the effective concentration.
Table 6 shows the results. Test Example 6, Antifungal Test on Wood Compounds Tested Preparation Example 1 (3% dichloroglyoxime diacetate (1) D
Formulation Example 2 (5% cyclologlyoxime dihexanoate (3) DMF solution) Formulation Example 3 (5% bis (N-methylcarbamic acid) dichloroglyoxime (7) DMF solution) Comparative product G (25% Thiabendazole aqueous suspension (TBZ
-FL (Shinto Paint)) Note) DMF: N, N-dimethylformamide strain Aspergillus niger var. int
ermedius JCM1863 Cladosporium sladosporioi
des JCM6021 Chaetomium glo
bsum IF06347 Each of the preparation example product and the comparative product were each 0.1%, 0.5%,
An aqueous solution diluted to 1.0% is made (partially suspension), and a test piece of wood (cedar, 50 mm × 50 mm × 1 mm) is immersed for 10 minutes and air-dried. Put these pieces into a Petri dish,
1 ml of each mixed spore solution prepared according to ISZ2991
Each piece was sprinkled on a piece of wood, placed in a constant temperature / humidity chamber at a temperature of 28 ° C. and a humidity of 95%, and periodically observed. Table 7 shows the results.

[0050]

[Table 6]

[Table 7]

The comparative products in Table 6 are as follows. Comparative product compound name C: methylene dithiocyanate D: 2-bromo-2-nitro-1,3-propanediol E: 5-chloro-2-methyl-3-isothiazolone / 2
-Methyl-3-isothiazolone (9: 1) composition F: 2,2-dibromo-2-cyanoacetamide The evaluation in Table 7 is as follows. 3: No hyphal growth was observed in the inoculated portion of the test piece of wood. 2: The growth area of the mycelium observed in the inoculated portion of the test wood piece does not exceed 1/3 of the total area. 1: The growth area of the hyphae observed in the inoculated portion of the test piece exceeds 1/3 of the total area. From Table 7, it can be seen that the product of the present invention has a low active ingredient concentration,
In particular, Formulation Example 3, (Compound (7)) showed fungicidal efficacy equivalent to that of compound G (thiabendazole), a typical fungicide having a 5-fold concentration.

[0052]

According to the results of Test Examples 1 to 5, comparative products A to
F, in particular C to F, is a typical drug currently used, but it has become clear that none of them has both bactericidal and inhibitory effects effectively. As in the present invention products 1 to 13,
By esterifying the halogenated glyoxime,
It became clear that in addition to the strong sterilizing power, the inhibitory power also increased. By using the product of the present invention alone, sufficient efficacy can be achieved.

 ──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-62-195309 (JP, A) JP-B-43-20581 (JP, B1)

Claims (1)

(57) [Claims] (1) Formula 1: (Wherein X is a halogen, Y is the same or different halogen atom or a hydrogen atom as X; R ¹ and R ² are
Formyl, alkyl (C = 1 to 18) carbonyl, haloalkylcarbonyl, alkenylcarbonyl, haloalkenylcarbonyl, alkoxycarbonyl, haloalkoxycarbonyl, alkoxycarbonylcarbonyl, alkoxycarbonylalkylcarbonyl, cycloalkylcarbonyl, unsubstituted or one or more halogen A nitro group, an arylcarbonyl substituted with a cyano group, unsubstituted or one or more halogen, a nitro group, an aryloxycarbonyl substituted with a cyano group, an unsubstituted or one or more halogen, a nitro group, a cyano group. Substituted arylalkylcarbonyl, alkylaminocarbonyl,
A carbonyl group selected from the group consisting of unsubstituted or one or more halogen, nitro group, arylaminocarbonyl substituted with a cyano group, and a 5- or 6-membered heterocyclic carbonyl containing one or more heteroatoms, R ¹ and R ² are the same or different carbonyl groups, or R ¹ and R ²
Wherein at least one of the above is the carbonyl and the other is a hydrogen atom) as an active ingredient. [0001]