JPS6247841B2 - - Google Patents

Description

[Detailed description of the invention]

The present invention relates to a preservative and fungicide containing a novel compound, a tetraarylboron-ammonium complex, as an active ingredient. More specifically, the present invention relates to the general formula () (In the formula, R ₁ represents a hydrogen atom, a halogen atom, or a lower alkyl group, R ₂ represents a halogen atom, a lower alkyl group, or a lower alkenyl group,
The present invention provides a preservative and fungicide characterized by containing as an active ingredient a tetraarylboron-ammonium complex represented by R ₃ represents imidazole which may be substituted with pyridine or a lower alkyl group. Traditionally, arylboron compounds have the general formula () (In the formula, X represents a potassium atom, an ammonium group, or a quaternized organic nitrogen group, but the organic nitrogen group may further form a heterocycle containing a nitrogen atom.) Compound (see Japanese Patent Publication No. 54-1571) and general formula () (In the formula, Y represents a hydrogen atom, a halogen atom, or a lower alkyl group) (see US Pat. No. 3,211,679)
is known for its use as an underwater antifouling agent. However, it is not known to be effective as an industrial preservative and fungicide. The present inventors have conducted extensive research into the use of phenylboron compounds as preservatives and fungicides. As a result, the novel tetraarylboron-ammonium complex represented by the general formula () has excellent antibacterial properties against molds such as Aspergillus, Penicillium, Rhizopus, and Fusarium, bacteria such as Bacillus and Pseudomonas, and yeasts. As a non-medical sterilizer and fungicide,
The present invention was completed based on the finding that it is particularly useful as an industrial preservative and fungicide. The tetraarylboron-ammonium complex, which is the active ingredient of the present invention, is chemically stable, exhibits sufficient bactericidal and antifungal effects in acidic and alkaline regions, and does not precipitate even when various metal salts are present together. It is advantageous from a practical standpoint as a sterilizing, disinfecting, preservative, and fungicidal agent because there is no fear of coloring or staining, and it can also be incorporated into plastics. In the compound of general formula (), when R ₁ and R ₂ are halogen atoms, they are preferably bromine, chlorine or fluorine, and R ₁ and R ₂ have 1 to 6 carbon atoms.
When it is a lower alkyl group, it is preferably a methyl group, ethyl group, propyl group, isopropyl group, butyl group, or isobutyl group, and R ₂ has 2 carbon atoms.
-6 lower alkenyl groups are preferably vinyl groups. (R ₃ H) is in the form of a quaternized ammonium group, such as pyridinium,
Preference is given to forming imidazolium, methylimidazolium. Next, Table 1 shows preferred examples of the tetraphenylboron-ammonium complex which is the active ingredient compound of the present invention. The compound numbers shown in Table 1 are also referred to in the Examples and Test Examples herein.

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[Table] The compound of the general formula () can be produced based on the following reaction formula by reacting sodium tetraarylboron of the general formula () with a hydrogen halide salt of a heterocyclic amine of the general formula (). (In the formula, X represents a halogen atom, R ₁ , R ₂ ,
R ₃ has the same meaning as above) The method for producing the compound of general formula (1) will be explained in detail below. First, the synthesis of sodium tetraarylboron of the general formula () used as a raw material in the production of the compound of the general formula () is carried out as follows. First, in order to synthesize a compound in which R ₁ and R ₂ represent the same group in the general formula (), the formula

[Formula] (However, R ₁ and X have the same meanings as above) 4 molar ratio or an excess amount of arylmagnesium halide

In a diethyl ether or tetrahydrofuran solution containing a 4 molar ratio or an excess amount of aryllithium represented by the formula, a 1 molar ratio of a diethyl ether complex of boron trifluoride is added as is or diluted with a solvent such as toluene. The resulting solution was added dropwise while stirring and cooling, and the mixture was allowed to react under reflux conditions for 1 hour. Next, while cooling and stirring the reaction solution, an aqueous solution of excess common salt, sodium carbonate, sodium hydroxide, etc. is added dropwise as a sodium source. After the reaction is complete, separate the upper organic layer and distill off the solvent to obtain white crystals, which are washed with a non-polar solvent such as toluene and dried to obtain the desired product represented by the general formula (). Sodium tetraarylboron is obtained as white crystals. If purification is required, the white crystals may be recrystallized using a lower alkanol solvent such as ethanol or isopropyl alcohol. Furthermore, in order to synthesize an asymmetric tetraarylboron compound in which R ₁ and R ₂ are different groups in the general formula (), first, an arylmagnesium halide or an aryllithium halide is reacted with boron trifluoride using the same method as above. After that, the formula is obtained from the reaction solution.

Either the symmetrical triarylboron represented by the formula is isolated or the molar ratio of these reactants is strictly controlled at 3:1 from the beginning of the reaction between arylmagnesium halide or aryllithium and boron trifluoride. After synthesizing triarylboron, an aryl group having a substituent R ₂ different from substituent R ₁ on the aryl group of triarylboron

When [Formula] is introduced, an asymmetric tetraarylboron is synthesized. Sodium tetraarylboron of the general formula () thus obtained and a hydrogen halide salt of a heterocyclic amine of the general formula () were mixed with methanol,
The reaction is completed by simply dissolving it in a lower alkanol such as ethanol or isopropyl alcohol, a ketone such as acetone, or an inert polar solvent such as water, and mixing and stirring at a temperature of 10 to 60°C for 30 minutes to 2 hours. As the reaction solvent, the above-mentioned solvents may be used alone or in combination. In addition, if the reaction product precipitates in the solvent as crystals, it can be separated, but usually the solvent is distilled off and concentrated, the crystals are separated, and the inorganic salts are removed by washing with water. After drying, a highly pure complex is obtained. The tetraarylboron-ammonium complex of the general formula () thus obtained can be further purified by recrystallization from a solvent such as methanol, ethanol, chloroform, dimethylformamide, etc., if necessary. Next, the method for producing the compound of general formula () and its raw material, sodium tetraarylboron, will be specifically explained using reference examples. Reference Example 1 Synthesis of sodium tetra(4-chlorophenyl)boron Tetrahydrofuran solution (800ml) of 4-chlorophenylmagnesium chloride (1.2 mol) synthesized from paradichlorobenzene and magnesium
was placed in a 2-volume, 4-necked flask, and 35.5 g (0.25 g of diethyl ether complex of boron trifluoride)
50 ml of a toluene solution of mol) was added dropwise at 20 to 30° C. while cooling and stirring the system in a water bath, and then the reaction mixture was heated under reflux conditions for 1 hour. After the reaction is complete, cool the reaction solution and add saturated aqueous sodium carbonate solution to it.
200ml was added dropwise. The separated organic layer was collected and the solvent was distilled off to obtain white crystals. Add 300ml of toluene to this to loosen and separate the crystals, and then
After washing twice with 100ml of toluene and drying, the melting point
106 g of the title compound as white crystals at 310°C (yield 88
%)was gotten. Reference Example 2 Synthesis of tetra(4-chlorophenyl)boron-pyridinium complex (compound No. 5) In a 500ml flask, dissolve 24.0g (0.05 mol) of sodium tetra(4-chlorophenyl)boron in 200ml of methanol. In addition to this
Pyridine hydrochloride 5.3 dissolved in 50ml methanol
g (0.05 mol) was added dropwise with stirring. After the dropwise addition was completed, stirring was continued for 1 hour to complete the reaction. Thereafter, the solvent in the reaction solution was distilled off, and 100 ml of water was added to the precipitated crystals to loosen them and separate the crystals. The crystals were further washed with water and dried to obtain 24.9 g (yield: 92.6%) of the title compound as white crystals with a melting point of 157-161°C. The elemental analysis values are as follows. Measured value Calculated value C 64.7% 64.9% H 4.1% 4.1% Reference example 3 Synthesis of tetra(4-chlorophenyl)boron-pyridinium complex (compound No. 5) Reference example using pyridine hydrochloride instead of pyridine hydrochloride The reaction was carried out according to 2, and the melting point was 157.
26.0 g of the title compound as white crystals at ~161°C
(yield 96.8%). The elemental analysis values are as follows. Measured value Calculated value C 64.6% 64.9% H 4.2% 4.1% Reference example 4 Tetra(4-fluorophenyl)boron-2-
Synthesis of methylimidazolium complex (compound No. 8) To a 100 ml flask was added 4.1 g (0.01 mol) of sodium tetra(4-fluorophenyl) boron dissolved in 40 ml of ethanol, and then dissolved in 20 ml of ethanol. 1.2 g (0.01 mol) of 2-methylimidazole hydrochloride was added dropwise while stirring. After the dropwise addition was completed, stirring was continued for 1 hour to complete the reaction. Thereafter, the solvent in the reaction solution was distilled off, and 50 ml of water was added to the precipitated crystals to loosen them and collect the crystals. The crystals were further washed with water and dried to obtain 4.3 g (yield: 9.02%) of the title compound as white crystals with a melting point of 205-207°C. The elemental analysis values are as follows. Measured value Calculated value C 70.5% 70.9% H 5.0% 4.9% Reference example 5 Tetra(4-fluorophenyl)boron-2-
Synthesis of methylimidazolium complex (compound No. 8) Using isopropyl alcohol as a reaction solvent,
The procedure was carried out according to Reference Example 4 to obtain 4.4 g of the title compound as white crystals with a melting point of 205-207°C (yield 92.9).
%) was obtained. The elemental analysis values are as follows. Measured value Calculated value C 70.5% 70.9% H 5.0% 4.9% Reference example 6 Synthesis of tetra(4-methylphenyl)boron-pyridium complex (compound No. 1) Tetra(4-methylphenyl)boron sodium 19.9 in a 500ml flask g (0.05 mol)
was dissolved in 200 ml of tetrahydrofuran, and 50 ml of an aqueous solution containing 4.0 g (0.05 mol) of pyridine and an equimolar amount of hydrochloric acid was added dropwise with stirring. Below, the melting point was determined by the same treatment as in Reference Example 2.
20.8 g of the title compound as white crystals at 183-185°C
(91.3%). The elemental analysis values are as follows. Measured value Calculated value C 86.8% 87.0% H 7.4% 7.5% Reference example 7 Triphenyl-(4-vinyl)phenylboron-2-methylimidazolium complex (Compound No.
Synthesis of 10) When triphenyl-(4-allyl)phenylboron sodium and 2-methylimidazole hydrochloride are reacted in the same manner as in Reference Example 4 using acetone as the reaction solvent, white crystals with a melting point of 234-236°C are obtained. 20.0 g (yield 93.7%) of the title compound was obtained. The elemental analysis values are as follows. Measured value Calculated value C 84.1% 84.2% H 6.9% 6.8% Another example of the tetraarylboron-ammonium complex of the present invention having the general formula () shown in Table 1 was also prepared by the same method as in the reference example. manufactured. In carrying out the present invention, in order to efficiently exhibit the excellent antiseptic and antifungal effect of the compound represented by the general formula (), the tetraarylboron-ammonium complex represented by the general formula () is prepared into an emulsion according to a conventional method. It may be formulated into a flowable agent (sol), a wettable powder, a liquid agent, etc., and used in the same manner as general antiseptic and fungicides, and is not limited to any special usage. Further, the tetraarylboron-ammonium complex of the general formula () can be used by appropriately selecting its concentration depending on the object of antiseptic and mold protection. Furthermore, the preservative and fungicide of the present invention can be mixed or used in combination with other known industrial preservative and fungicides. These known preservatives and fungicides include, for example, their chemical names: zinc diethylthiol carbamate, tetramethylthiuram disulfide, tetrachloroisophthalonitrile, 2-(4-thiazolyl)benzimidazole, methylbenzimidazole carbamate, parachloro phenol,
4-Tetrahexylphenol, parachloro-metaxylenol, bis(2-pyridylthio-1-
oxide), 4-chlorophenyl-3-iodopropargyl formal, etc., but are not limited to these examples. The preservative and fungicidal agent of the present invention can also be used in combination with or in combination with an insecticidal compound for the purpose of preservative, fungicidal, and insecticidal (or insect repellent) purposes. Next, examples of formulations of the industrial preservative and fungicide of the present invention will be specifically illustrated with reference to Examples. Example 1 (Wettable powder) 20 parts of Compound No. 1, 7 parts of lauryl sulfate, and 73 parts of clay were uniformly mixed and ground.
A hydrating powder containing 20% of the active ingredient is obtained. Example 2 (Flowable agent) 20 parts of Compound No. 6, 2 parts of lauryl sulfate, 2 parts of xanthan gum, and 1 part of hydroxypropyl cellulose are uniformly mixed to obtain a flowable agent containing 20% of the active ingredient. Example 3 (Emulsion) 1 part of Compound No. 11, 47 parts of dimethyl sulfoxide, 50 parts of tetrahydrofuran, and 2 parts of Solpol 800A (trade name of an emulsifier manufactured by Toho Chemical Industry Co., Ltd.) were uniformly dissolved to dissolve the active ingredient. An emulsion containing 1% of Next, the tetraarylboron of the general formula ()
The usefulness of ammonium complexes as antiseptic and antifungal agents will be explained using test examples. Test Example 1 Antibacterial test against various fungi The test was based on the agar dilution smear method (streak method). In other words, among the various bacteria known to degrade industrial materials, potato decoction medium (PH5.8) is used for filamentous fungi, and bouillon agar medium (PH7.0) is used for bacteria. Sterilized water was added to each test microorganism that had been cultured in advance on a test tube slant medium, and the resulting spore suspension was streaked onto the drug-containing medium using a platinum loop. Then, each culture medium was incubated at a temperature of 28 ± 2°C for 96 hours, and the presence or absence of growth of each bacteria was examined. ppm) was calculated. The results are shown in Table 2.

[Table] Test Example 2 Emulsion Paint Antifungal Effect Test A hydrating agent prepared according to Example 1 was added so that the active ingredient had a predetermined concentration of the emulsion paint, and the mixture was applied to wood chips and paper and air-dried. A mold resistance test was conducted in accordance with JIS Z2911-7 paint test. For wood chips, culture them and
After 1 day, 7 days, 14 days and natural storage (27℃, 98℃)
(% humidity) after 3 months, and for paper, 3 days, 7 days and 14 days after application, the degree of mold growth was investigated according to the following criteria. The results are shown in Tables 3 and 4. Mold occurrence investigation criteria 3: No mycelial growth is observed on the inoculated part of the sample or test piece. 2: The area of mycelia growth observed on the inoculated part of the sample or test piece does not exceed one-third of the total area. 1: The area of mycelia growth observed in the inoculated part of the sample or test piece exceeds one-third of the total area. Comparative drug A in Tables 3 and 4 contains 2% 2,4-thiazolylbenzimidazole and 1,2-benzisothiazoline-3 as active ingredients.
Comparative agent B is a commercially available fungicide containing 10% bis(tributyltin) oxide, and these comparative agents are also referred to in the following test examples.

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[Table] Test Example 3 Preservative effect test on glue A flowable agent prepared according to Example 2 was added to 9% carboxymethyl cellulose (hereinafter referred to as CMC) glue and 10% potato starch glue so that the active ingredient reached a predetermined concentration. After each was added and mixed uniformly, the mixture was placed in a synthetic resin cup, covered with aluminum foil, and stored in a constant temperature chamber (30°C). After 7 and 11 days of storage, the test paste was streak-cultured (at 37°C for 48 hours) on a bouillon agar medium, and the status of bacterial growth was investigated according to the following criteria. The results are shown in Tables 5 and 6. Investigation criteria +: Glue where bacteria have grown -: Glue where bacteria have not grown Comparative drug C contains 20% parachloromethaxylenol and 2-bromo 2- as active ingredients.
It is a commercially available fungicide containing 20% nitropropane-1,3-diol, and comparative drug D is
-Formula described in Publication No. 28579: Comparative drug E is tri-(p-fluorophenyl)borane pyridine represented by the formula described in the same publication: The latter two were used as comparative drugs because they have similar structures to the compounds of the present invention.

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[Table] Test Example 4 Wood fungicidal effect test The test method was conducted in accordance with the method for testing the efficacy of wood fungicides described in the Japan Wood Preservation Association Standard No. 2 (1979 edition). That is, an emulsion prepared according to Example 3 was diluted with xylene so that the active ingredient reached a predetermined concentration, and a piece of wood [2.5 cm x 2.5 cm x 0.5 cm in size] was placed in the emulsion, and a piece of potato was placed in front of the emulsion. Decoction (20% potato starch and 2% glucose)
Two types were used: one that was immersed in a PD medium (hereinafter referred to as PD medium) for 3 minutes to absorb the nutrient solution and dried at 60℃, and the other that was not immersed in such a PD medium and did not absorb the nutrient solution]. to absorb the drug. This piece of wood was then air-dried for two days and used as a test specimen. This specimen was placed in a Petri dish and cultured on a potato decoction agar medium specified in JIS Z2911.
ATCC9642, Penicillium funiculosum ATCC9644, Rizopus
stolonifer (Rhizopus stolonifer)
IFO6354, Aureobasidium pullulans IFO6353,
Using a brush, apply 1 ml of a mixed spore solution (a mixture of four types of single spore suspensions in equal amounts) of Gliocladium virens (ATCC9645) to the test specimen. Cover the Petri dish and culture at a temperature of 26±2°C and a humidity of 70-80%. The investigation was carried out after 3 days, 7 days, 14 days, 21 days and 28 days after culture.
After a day, the mold growth status of the test specimen was investigated according to the following criteria. The results are shown in Tables 7 and 8. Investigation criteria 3: No mold growth is observed on the test specimen. 2: Mold growth is observed only on the sides of the test piece. 1: Mold growth is observed on one-third or less of the area of the upper surface of the test piece. 0: Mold growth is observed on one-third or more of the area of the upper surface of the test piece. In addition, comparative drug F contains 2,4- as an active ingredient.
It is a commercially available fungicide containing 2% thiazolylbenzimidazole, 4% 1,2-benzisothiazolin-3-one, and 1% diiodomethyl paratolyl sulfone.

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Claims (1)

[Claims] 1. General formula (In the formula, R ₁ represents a hydrogen atom, a halogen atom, or a lower alkyl group, R ₂ represents a halogen atom, a lower alkyl group, or a lower alkenyl group,
A preservative and fungicide containing a tetraarylboron-ammonium complex as an active ingredient (R ₃ represents imidazole which may be substituted with pyridine or a lower alkyl group).