JP3459086B2 - Disinfectant algicide - Google Patents

Description

Detailed Description of the Invention

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a fungicidal algicidal agent containing a tetraalkylphosphonium salt as an active ingredient.

[0002]

2. Description of the Related Art At present, not only for medical use but also for industrial use,
A great variety of fungicides are used in various fields such as agriculture and food. Most of the fungicides used so far have been highly toxic fungicides, but recently, due to environmental pollution problems and economic problems, sufficient antibacterial activity is exhibited even at low use concentrations. Development of the bactericide shown is desired. Further, it has been conventionally known that a phosphonium salt compound is used as an active ingredient of an antibacterial preparation, and has a broad activity spectrum against bacteria, fungi and algae. These are used as sterilizing agents for general industrial materials, industrial water, process water for producing pulp and paper, water for use, and are disclosed in, for example, U.S. Pat. No. 3,281,365, JP-A-57-204286, and JP-A-57-204286. 62-1149
03, JP-A-63-60903, JP-A-2
No. 24090, for example. Among them, tetrakis hydroxymethylphosphonium sulfate (hereinafter, TH
PS is a water treatment germicide (trademark: Torside P).
S) is commercially available. In addition, nitrogen-containing compounds structurally similar to phosphonium salt compounds, especially quaternary ammonium salts and amine salts are also well known as germicides,
For example, alkyldimethylbenzylammonium chloride (benzalkonium chloride) and di-n-decyldimethylammonium chloride are mainly used.

[0003]

However, the above-mentioned phosphonium salt compound is still insufficient in the bactericidal and algaecidal effect by short-time contact. Particularly in a system in which a high concentration of organic substances is present, the bactericidal / algicidal effect is remarkably reduced, and the use thereof is extremely limited. Further, although the quaternary ammonium salt compound has a bactericidal effect to some extent, it has a property of easily foaming at a certain use concentration, and therefore its use is also limited.
Moreover, since the quaternary ammonium salt compound has a property of being easily adsorbed on the surface of a negatively charged substance,
It has the drawback of lowering the drug concentration due to adsorption and thus the bactericidal effect. The present inventors have solved the above-mentioned problems, have a broad spectrum of sterilization and algicidal action, and have sufficient bactericidal and algicidal effect by short-time contact, and can be applied to a wide range of fields including medical fields. It is intended to provide a bactericidal and algicidal agent.

[0004]

As a result of earnest studies, the present inventors have found that certain phosphonium salt compounds are extremely powerful bactericidal and algaecidal in comparison with closely related phosphonium salt compounds and quaternary ammonium salts. It has a strong power and a wide spectrum of sterilization and algae killing, and even when it is vigorously stirred like a cooling tower,
The present invention has been completed by finding that the foaming is small and the odor is small. That is, the bactericidal / algicidal agent to be provided by the present invention is firstly represented by the following general formula (1) R ¹ ₃ R ² P ⁺ X ⁻ (1) (wherein R ¹ has 1 to 3 carbon atoms ) . An alkyl group, R ² is an alkyl group having 12 to 18 carbon atoms, and X ⁻ is an alkyl group.
Phosphonate ion, substituted or unsubstituted benzenesulfonic acid
A tetraalkylphosphonium salt represented by
A bactericidal and algicidal composition containing as an active ingredient.

Secondly, triethyl n-hexadecylphos
Killing with phonium p-toluenesulfonate as an active ingredient
It is a fungal algaecide.

Thirdly , the following general formula (2) R ¹ ₃ R ² P ⁺ X ⁻ (2) (wherein R ¹ is an alkyl group having 1 to 3 carbon atoms , R ² is a carbon atom ).
An alkyl group having 12 to 18 elementary atoms, X ⁻ is F, Cl or
Is a halogen atom of Br, an anion of an inorganic acid or an organic acid
The tetraalkylphosphonium salt represented by
It is an algicidal agent.

The present invention will be further described below. In the formula (1), which is the active ingredient of the bactericidal / algicidal agent of the present invention, in the formula, R ¹
Is a methyl group, an ethyl group, a propyl group or the like having 1 to 10 carbon atoms.
3 is an alkyl group. R ² is an alkyl group having 12 to 18 carbon atoms such as dodecyl group, tetradecyl group, hexadecyl group, octadecyl group. In addition, in equation (1)
Oite, X ^- is an alkyl such as methanesulfonate ion
Sulfonate ion; such as p-benzene sulfonate ion
It is a substituted or unsubstituted benzenesulfonate ion.
As such a tetraalkylphosphonium salt, for example,
For example, triethyl n-hexadecylphosphonium methane
Ruphonate, triethyl n-hexadecylphosphonium
p-toluene sulfonate, tri-n-propyl n-hex
Sadecylphosphonium methanesulfonate, tri-n-type
Ropyl n-hexadecylphosphonium p-toluenesul
Examples include honate. Tet according to the above formula (1)
In the laalkylphosphonium salt, for example, R ^{1 in the} formula is
R ² having 16 or less carbon atoms and 16 to 18 carbon atoms
The combination of kill groups shows excellent bactericidal / algicidal activity, especially
Liethyl n-hexadecylphosphonium p-toluene
The bactericidal and algicidal effect of lephonate is high.

Further , it is an active ingredient of the algicidal agent of the present invention.
In the formula (2), R ¹ is a methyl group, an ethyl group or a group
It is an alkyl group having 1 to 3 carbon atoms such as a ropyl group. Well
R ² is dodecyl group, tetradecyl group, hexadecyl group
Group, octadecyl group, etc., having 12 to 18 carbon atoms
It is a ru basis. X ⁻ is, for example, a halogen ion of fluorine, chlorine or bromine; an aliphatic carboxylate ion such as formic acid, acetic acid, oxalic acid, benzoic acid, phthalic acid or the like; an aromatic carboxylate ion; a sulfate ion; a phosphate ion; methyl or dimethylphosphorus. Alkyl phosphate ester ions such as acid ester ions, ethyl or diethyl phosphate ester ions, butyl or dibutyl phosphate ester ions; antimony fluoride ion, phosphorus fluoride ion, arsenic fluoride ion, boron fluoride ion, perchlorate ion; Alkylsulfonate ion such as methanesulfonate ion; Substituted or unsubstituted benzenesulfonate ion such as p-benzenesulfonate ion; 1-Hydroxyorgano-1,1-
Diphosphonate ion, 1-hydroxyethane-1,1-
Examples thereof include inorganic or organic anions such as diphosphonate ion, and among them, halogen ion of fluorine, chlorine or bromine, alkylsulfonate ion, and substituted or unsubstituted benzenesulfonate ion are preferable. In particular, an alkyl sulfonate ion, a substituted or unsubstituted benzene sulfonate ion, and an alkyl phosphate ester ion are preferable because they are less corrosive to metals.

Examples of such tetraalkylphosphonium salts include trimethyl n-dodecylphosphonium chloride and trimethyl n-tetradecylphosphonium chloride.
Loride, trimethyl n-octadecylphosphonium chloride, triethyl n-dodecylphosphonium chloride
Id, triethyl n-tetradecylphosphonium chloride, triethyl n-hexadecylphosphonium chloride, triethyl n-hexadecylphosphonium fluoride
Ride, triethyl n-octadecyl phosphonium chloride, tri n-propyl n-tetradecyl phosphonium chloride, tri n-propyl n-hexadecyl phosphonium chloride, tri n-propyl n-octadecyl phosphonium chloride, triethyl n-hexadecyl phosphonium bromide, triethyl n-hexadecylphosphonium tetrafluoroborate, triethyl n-
Octadecylphosphonium perchlorate, triethyl n-tetradecylphosphonium diethyl phosphate,
Triethyl n-hexadecylphosphonium methanesulfonate, triethyl n-hexadecylphosphonium p-
Toluene sulfonate, triethyl n-hexadecyl phosphonium acetate, tri n-propyl n-hexadecyl phosphonium methane sulfonate, tri n-propyl n-hexadecyl phosphonium p-toluene sulfonate, etc. are mentioned.

In the tetraalkylphosphonium salt according to the above formula (2) , for example, a combination of R ^{1 in the} formula with 2 or less carbon atoms and R ² with an alkyl group having 16 to 18 carbon atoms shows excellent algicidal activity. In particular, the bactericidal and algicidal effect of triethyl n-hexadecylphosphonium chloride is high.

Method for producing bactericidal / algicidal agent The tetraalkylphosphonium salt, which is the bactericidal / algicidal agent of the present invention, may be produced by any method, but one example is shown below as an industrial production method. A trialkylphosphine represented by the general formula (3) R ¹ ₃ P (wherein R ¹ has the same meaning as described above), and a general formula (4) R ² X (wherein R ² has the same meaning as described above ). And X represents a halogen atom of F, Cl or Br.), And the bactericidal and algicidal agent of the present invention can be obtained. When the anion is an inorganic acid or an organic acid, it can be obtained by reacting the tetraalkylphosphonium halide halide obtained in the above reaction with, for example, an alkyl sulfonate at room temperature. The reaction of the compounds of the above general formulas (3) and (4) is preferably carried out in the presence of a solvent at the reflux temperature of the solvent for 15 to 48 hours.
Further, the alkyl halide is preferably used in an equimolar to 5-fold molar amount with respect to the trialkylphosphine.

Suitable organic solvents include n-hexane,
Examples thereof include n-heptane, n-octane, benzene, toluene, xylene, n-propanol and n-butanol. The bactericidal / algicidal agent according to the present invention may be used in combination with other bactericidal / algicidal agents, if necessary. For example, quaternary ammonium salts such as dimethyldi-n-decyl ammonium chloride, benzyl dimethyl n-dodecyl ammonium chloride, benzyl dimethyl n-tetradecyl ammonium chloride, 5-chloro-
2-Methyl-4-isothiazolin-3-one, 2-bromo-2-nitropropane-1,3-diol, 1,5-pentanediol, phenol, chlorhexidine, povidone iodine, alkyl chloride polyaminoethyleneglycine, organic chlorine, etc. One type or two or more types of bactericidal agents and inorganic antibacterial agents such as silver-substituted zeolite and silver-substituted apatite may be used in combination.

In addition, in the preparation, auxiliary agents such as a surface active agent, a binder, a colorant, a dispersant and a wetting agent may be added, if necessary. In particular, a surfactant can be added in order to enhance the cleaning effect, but the surfactant is preferably a nonionic surfactant, such as polyethylene glycol such as polyoxyethylene alkylphenyl ether, sorbitan acid fatty acid ester, etc. Examples thereof include amides such as polyhydric alcohols and fatty acid alkylolamides. The bactericidal / algicidal agent according to the present invention has various industrial fields depending on the form of its formulation, for example, a slime preventive or control agent in papermaking, water, fats and oils, emulsions,
It can impart antiseptic and bactericidal functions to paper, rubber, plastics, fibers, films, paints and the like.

[0014]

The bactericidal / algicidal agent of the present invention exhibits a broad activity spectrum effective against various bacteria, fungi, algae, viruses and the like, and has an excellent bactericidal activity especially against resistant Staphylococcus aureus (MRSA). Shows, for example, a bactericidal and growth inhibitory effect against bacteria, a fungicidal effect against fungi ,
It has an algicidal effect on algae . The minimum bactericidal concentration (MBC) is the type of tetraalkylphosphonium salt,
The concentration of tetraalkylphosphonium salt is 0, though it is not uniform depending on the type of preparation or various kinds of bacteria and environment.
It is exerted at 1 ppm or more, and generally has extremely high bactericidal activity as compared with well-known bactericides based on phosphonium salts and quaternary ammonium salts. Moreover, the tetraalkylphosphonium salt according to the present invention is more stable against heat than the quaternary ammonium salt compound and other organic compounds, and has a high decomposition temperature of about 350 ° C. It is also stable.

[0015]

EXAMPLES The present invention will be further described below with reference to examples. Production Example 1 (Synthesis of triethyl n-hexadecylphosphonium chloride) 37.19 g (0.315 mol) of triethylphosphine and 134.99 g of toluene were added to and dissolved in a 300 ml flask while sufficiently substituting with nitrogen. Then 1-chlorohexadecane (95.0%) 95.08 g (0.364)
mol) is added. The reaction was carried out by stirring for 30 hours while refluxing the liquid temperature in the flask near the boiling temperature of toluene (118 to 120 ° C). The completion of the reaction was confirmed by a color reaction between unreacted triethylphosphine and carbon disulfide. After completion of the reaction, the mixture was cooled to room temperature to precipitate crystals. The precipitated crystals were dissolved in diethyl ether, further cooled to 5 ° C to reprecipitate the crystals, and separated by filtration. After repeating the same recrystallization operation several times, the obtained crystal was vacuum dried at room temperature (5 Torr, 5 hours). As a result, 24.1 g of white crystal triethyl n-hexadecylphosphonium chloride (purity: 98. 0%, yield 19.
8%). The purity was measured by the perchloric acid titration method. The compound was identified by ¹ H-NMR and FAB.
/ Mass.

Production Examples 2 to 8 and Comparative Production Examples 1 to 4 The same operation as in Production Example 1 was carried out using various trialkylphosphines instead of triethylphosphine and various alkyl halides instead of 1-chlorohexadecane. The tetraalkylphosphonium salt shown in Table 1 was obtained.

Production Example 9 (Synthesis of triethyl n-hexadecylphosphonium p-toluene sulfonate) 9.58 g (0.59%) of triethyl n-hexadecylphosphonium chloride (98.91%) was put in a 200 ml flask.
(025 mol) is charged and dissolved with 100 ml of demineralized water. Next, sodium p-toluenesulfonate (98.
(0%) 4.95 g (0.025 mol) was added, and the mixture was stirred at room temperature for 5 hours. After completion of the reaction, the lower layer of the reaction solution separated into two layers was separated, and the remaining solution in the reaction vessel was washed with demineralized water. Then, after sufficiently washing with n-hexane, n-hexane was recovered under reduced pressure at 80 ° C. and 5 Torr. As a result, viscous transparent liquid triethyl n-hexadecylphosphonium p-toluenesulfonate 12.78 g (purity 9
7.18%, yield 92.48%) was obtained. The purity was measured by the perchloric acid titration method. To confirm the compound,
^It was carried out by ¹ H-NMR and FAB / MASS.

Production Example 10-12 The same operation as in Production Example 9 was carried out by using various tetraalkylphosphonium chlorides instead of triethyl n-hexadecylphosphonium chloride and various sulfonates instead of sodium p-toluenesulfonate. Then, the tetraalkylphosphonium salt shown in Table 1 was obtained. Table 1 shows the compounds obtained in Production Examples 1 to 12 and Comparative Preparation Examples 1 to 4.

[0019] conducted tests 1 microbiocidal tested tetraalkylphosphonium salt obtained in Production Examples 1 to 12 and Comparative Preparation Examples 1 to 4 (bacterial, bactericidal test against filamentous fungi).
The types of strains used in the test, their test methods, and the results are shown below. (1) Strains to be tested 7 types of bacteria and 2 types of filamentous fungi, which are particularly harmful to industry and hygiene, were selected, and 9 types of strains shown below were tested. Bacteria Bs: Bacillus subtilis IFO 3007 (Bacillus subtilis) Ec: Escherichia coli NIHJ (E. coli) Pa: Pseudomonus aeruginosa IAM 1054 (Pseudomonas aeruginosa) Sa1: Staphylococcus aureus ATCC 6538p (Staphylococcus aureus) Sa2: Staurelocus Methicillin- resistant Staphylococcus aureus) Ss: Shigella sonnei (Shigella) St: Salmonella typhimurium (Agrobacterium typhimurium) filamentous fungus An: Aspergillus niger ATCC 6275 (black mold) Ps: Penicillium strepii IAM

(2) Test method and its results (2-1) Test method The samples of Production Examples 1-8 and Comparative Production Examples 1-4 were accurately weighed to prepare 200 μg / ml aqueous solutions. Using this preparation, 200, 100, 50, 25, 10,
Sample solutions were diluted to 5, 2.5 and 1 μg / ml concentrations, respectively. Next, the test strains stored in test tubes were added to 1 ml of 10 ml of normal broth medium (three grams of meat extract, 10 g of peptone and 5 g of sodium chloride dissolved in 1,000 ml of water).
After taking platinum loops and shaking culture at 30 ° C for 48 hours, 2
The solution stored at 0 ° C was used as the culture solution of the test bacteria. 9 ml of the obtained sample solution was placed in a sterilized 10 ml L-shaped test tube, and 1 ml of the culture solution of the above-mentioned test bacteria was ingested into the sample solution at 30 ° C. for 3 days.
It was left to act for 0 minutes. After the action, add 1 ml of this solution to 10 parts of sterilized water.
After pouring it into 0 ml and uniformly diluting it, 1 ml of this diluted solution was taken as a working solution. The strains in these working solutions were further cultured by the methods described below, and the bactericidal activity of each sample was determined.

(2-2) Bacterial culture Bacteria: 10 μl of the working solution was placed in a sterilized petri dish, and 15 ml of a bacterial culture medium (Nissui Pharmaceutical Tryptosoya agar medium) was poured and solidified and cultured at 30 ° C. for 2 days. Filamentous bacterium: For filamentous fungus on sterile petri dish (Nissui Pharmaceutical potato dextrose agar medium)
After pouring 15 ml to solidify, add 10 μl of working solution to 30 ° C.
The cells were cultured for 4 days. (2-3) Bactericidal Power Judgment Method and Results The bactericidal power was evaluated by visually observing colonies of each bacterium and filamentous fungus, and killing those in which the medium was transparent and colonies could not be judged. The lowest concentration of the sample solution in which the bacteria have been killed is the minimum bactericidal concentration (MBC) of the compound,
The results are shown in Table 1 . Also, 3 at a drug concentration of 1 ppm
The results of measuring the viable cell count after 0 minutes are shown in Table 2 .

[0022]

[Table 1]

[0023]

[Table 2]

[0024] it was carried out algicidal force tested tetraalkylphosphonium salt obtained in Test 2 (algicidal force test on algae) Preparation 12 and Comparative Production Examples 1 to 4.
The types of algae used in the test, their test methods, and the results are shown below. (1) subjected試藻such green algae Chlorella vulgaris Chlorella vulgaris blue-green algae Oscillatoria-Kurorina Oscillatoria chlor
ina (2) Test method and its result The above green algae and cyanobacteria are inoculated in Detmer medium and cultured in a climate machine at 25 ° C to prepare a test solution. Next, a 1/3 dilution of Detmer's medium [Ca (NO ₃ ) _{2
1.0g, KCl 0.25g, MgSO 4 ·} 7H 2 O 0.2
5 g, KH ₂ PO ₄ 0.25 g, FeCl ₃ 0.002 g /
[H ₂ O 3L], a chemical solution and a test solution are added so as to have a predetermined concentration, and the mixture is cultured in an artificial weather machine at 25 ° C. Culturing is continuously performed with a stirrer. The decolorized state of algae is observed after 48 hours, and the lowest concentration is defined as the minimum algicidal concentration. Table 3 shows the minimum algicidal concentration of each drug.

[0025]

[Table 3]

[0026] was confirmed whether the test 3 (foaming and Testing of smell) for tetraalkylphosphonium salts and comparative agent obtained in Production Example 1-12 foaming test and odor. (1) Test method 50 ml of 0.2% aqueous solution of each drug was prepared and 100 ml
Place in a graduated cylinder with a common stopper and shake for 2 minutes, then
The foam height is measured after standing for 0 to 60 minutes. Also, the presence or absence of odor was confirmed. (2) Test results Table 4 shows the test results.

[0027]

[Table 4]

[0028]

The bactericidal / algicidal agent according to the present invention exhibits sufficient bactericidal / algicidal activity even at a low use concentration, and at least 0.1 p
The effect is shown at a concentration of pm. Moreover, compared to conventional phosphonium salt compounds and quaternary ammonium salt compounds
Foaming is small, for example, even when vigorously be stirred, such as cooling towers, less foaming, a and low odor microbicidal and algicidal. The bactericidal and algicidal agent of the present invention has recently been attracting attention as a nosocomial infectious agent.
Since it has bactericidal power against A), it is possible to provide an effective means for this countermeasure. In addition, it can be widely applied to fields such as industrial water, process water for manufacturing pulp and paper, agriculture, and food, as well as medical use.

Front page continuation (72) Inventor Seiji Shimura 9-15-1, Kameido, Koto-ku, Tokyo Nippon Kagaku Kogyo Co., Ltd. Research & Development Headquarters (72) Inventor Issei Tanaka 328 Shionoitahamano, Fukuda-cho, Iwata-gun, Shizuoka Address K-ai Kasei Co., Ltd. (72) Inventor Koichi Iwabuchi Shioshin Hamada, Fukuda-cho, Iwata-gun, Shizuoka 328 Ka-i Kasei Co., Ltd. (72) Inventor Yoshihiro Konagai Fukuda-cho, Iwata-gun Shizuoka Tahamano No. 328 Kai Kasei Co., Ltd. (56) Reference JP-A-57-204286 (JP, A) JP-A-62-26209 (JP, A) US Patent 3281365 (US, A) (58) Investigation Areas (Int.Cl. ⁷ , DB name) A01N 57/34 A01N 57/20 A01N 57/22 C07F 9/54

Claims (6)

(57) [Claims] 1. A compound represented by the following general formula (1): R ¹ ₃ R ² P ⁺ X ⁻ (wherein R ¹ is an alkyl group having 1 to 3 carbon atoms, R ² is an alkyl group having 12 to 18 carbon atoms, and X is ^- alkyl sulfates
Phosphonate ion, substituted or unsubstituted benzenesulfonic acid
On ) is a fungicidal algicidal agent containing a tetraalkylphosphonium salt represented by the formula (1) as an active ingredient. 2. Triethyl n-hexadecylphosphonium
A fungicidal algicidal agent containing p-toluenesulfonate as an active ingredient. 3. Less tetraalkylphosphonium salt
The bactericidal algaecide according to claim 1, which contains 0.1 ppm each.
Agent. 4. A compound represented by the following general formula (2): R ¹ ₃ R ² P ⁺ X ⁻ (wherein R ¹ is an alkyl group having 1 to 3 carbon atoms, and R ² is carbon.
An alkyl group having 12 to 18 elementary atoms, X ⁻ is F, Cl or
Is a halogen atom of Br, an anion of an inorganic acid or an organic acid
The tetraalkylphosphonium salt represented by
An algaecide as an active ingredient. 5. The anion of the general formula (2) is F, Cl or
Is a halogen of Br, The algicidal agent of Claim 4. 6. A tetraalkylphosphonium salt is trie
Chill n-hexadecylphosphonium chloride
The algicidal agent according to claim 4.