JPH06321717A - Germicidal algicide - Google Patents

Abstract

PURPOSE:To obtain a germicidal algicide, having extremely strong germicidal and algicidal activities and wide germicidal and algicidal spectram with hardly any foaming even in the case of violent stirring and malodor and containing a specific benzylphosphonium salt compound as an active ingredient. CONSTITUTION:This germicidal algicide contains a benzylphosphonium salt expressed by the formula (R<1> to R<3> are 1-22C hydroxyl group-substituted or unsubstituted alkyl; R<4> is H, hydroxyl, nitro, 1-4C alkyl or halogen; X is anion of inorganic or organic acid) as an active ingredient. The anion in the compound expressed by the formula is preferably a halide ion. For example, dimethyl-n-dodecylbenzylphosphonium chloride is cited as the benzylphosphonium salt expressed by the formula. This germicidal algicide is capable of manifesting effective wide active spectrom for various bacteria, fungi, algae and viruses and especially excellent germicidal activity even against methicillin-resistant Staphylocccus aureus (MRSA). For example, the germicidal effects and growth suppressing effects on the bacteria and algicidal effects on the algae are manifested.

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 benzylphosphonium salt as an active ingredient.

[0002]

2. Description of the Related Art At present, a great variety of bactericides are used not only for medical purposes but also in various fields such as industry, agriculture and food. Most of the fungicides used so far are
Although it was a highly toxic bactericide, recently, due to environmental pollution problems and economical problems, it has been desired to develop a bactericide that exhibits a sufficient antibacterial activity even at a low concentration. Also,
Conventionally, phosphonium salt compounds are known to be used as an active ingredient of antibacterial agents, and bacteria, fungi,
It has a broad spectrum of activity against algae. These are used as bactericides for general industrial materials, industrial water, process water for producing pulp and paper, water, and the like, for example, U.S. Pat. No. 3,281,365, JP-A-57-2.
04286, JP-A-62-114903,
JP-A-63-60903, JP-A-2-24009
There are publications such as No. 0. Among them, tetrakis hydroxymethylphosphonium sulfate (hereinafter abbreviated as THPS)
Is commercially available as a disinfectant for water treatment (trademark: Torside PS). Nitrogen-containing compounds that are structurally similar to phosphonium salt compounds, especially quaternary ammonium salts and amine salts, are also well known as bactericides, such as alkyldimethylbenzylammonium chloride (benzalkonium chloride) and di-n. -Decyldimethylammonium chloride and the like 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 problems, have a wide spectrum of bactericidal and algicidal effects, and have a sufficient bactericidal and algicidal effect by contact for a short time, and have a wide range of environmental hygiene and medical applications. It is an object of the present invention to provide a bactericidal algicidal agent applicable to the field.

[0004]

As a result of intensive studies, the present inventors have found that certain benzylphosphonium salt compounds have extremely strong bactericidal killing as compared with closely related phosphonium salt compounds and quaternary ammonium salts. The present invention was completed based on the finding that it has algae power and a broad spectrum of bactericidal / algicidal activity, and has little foaming and little odor even when vigorously stirred as in a cooling tower. That is, the bactericidal / algicidal agent to be provided by the present invention is represented by the following general formula (1):

[0005]

[Chemical 2]

(Wherein R ¹ , R ² and R ³ are a substituted or unsubstituted alkyl group having 1 to 22 carbon atoms, R ⁴ is a hydrogen atom, a hydroxyl group, or 1 to 12 carbon atoms)
4 is an alkyl group or halogen, and X ⁻ represents an inorganic or organic anion), and a benzylphosphonium salt represented by the formula) is used as an active ingredient.

The present invention will be further described below. In the general formula (1) which is an active ingredient of the fungicidal algicidal agent of the present invention, in the formula, R ¹ , R ² and R ³ are methyl group, ethyl group, propyl group, butyl group, octyl group, decyl group, tetradecyl group. , A hexadecyl group, an octadecyl group, a hydroxymethyl group, a hydroxyethyl group, a hydroxyoctyl group, a hydroxyoctadecyl group and the like, and a hydroxy group-substituted or unsubstituted alkyl group having 1 to 22 carbon atoms. Also, R
⁴ is a hydrogen atom, a hydroxyl group, a methyl group, an ethyl group,
Examples thereof include alkyl groups such as propyl group and butyl group, halogens such as chlorine, bromine and fluorine. Also, R ¹ , R
² and R ³ may or may not be the same group. X ⁻ is an inorganic or organic anion, for example, a halogen ion such as fluorine, chlorine, bromine or iodine,
Formic acid, acetic acid, carboxyl ion such as oxalic acid, sulfate ion, phosphate ion, methyl or dimethyl phosphate ion, ethyl or diethyl phosphate ion, antimony fluoride ion, phosphorus fluoride ion, arsenic fluoride ion, boron fluoride ion, Examples thereof include perchlorate ion, and halogen ion is preferable.

As such a benzylphosphonium salt,
For example, dimethyl n-dodecylbenzylphosphonium chloride, triethylbenzylphosphonium chloride, tri-n-butylbenzylphosphonium chloride,
Tri-n-hexylbenzylphosphonium chloride, tri-n-octylbenzylphosphonium chloride, p-
Ethylbenzyl dimethyl octadecylphosphonium chloride, p-ethylbenzyl tri-n-butylphosphonium chloride, p-ethylbenzyl tri-n-hexylphosphonium chloride, p-ethylbenzyl tri-n-octylphosphonium chloride, p-nitrobenzyl tri-n-butylphosphonium chloride , P-chlorobenzyl tri-n-butylphosphonium chloride p-chlorobenzyl tri-n-octylphosphonium chloride, p
-Bromobenzyl tri-n-butylphosphonium chloride, p-bromobenzyl tri-n-octylphosphonium chloride, dimethyl n-dodecylbenzylphosphonium bromide, triethylbenzylphosphonium bromide, p-ethylbenzyltrin-octylphosphonium bromide, p-ethylbenzyltri Examples thereof include n-octylphosphonium tetrafluoroborate.

In the benzylphosphonium salt according to the above (1), when ^{one of three} R ^{1 to} R ³ is different from the same kind, two have 1 to 3 carbon atoms and the other 1
One has a combination of 8 to 18 carbon atoms, and all three have the same kind, the number of carbon atoms is 6 or more, especially in the case of an alkyl group, a larger one having a hexyl group or more has a higher bactericidal / algicidal effect. Tends to become.

Method for producing bactericidal / algicidal agent of the present invention The benzylphosphonium salt which is the bactericidal / algicidal agent of the present invention is
Although it may be produced by any method, an example thereof is shown below as an industrial production method. A trialkylphosphine represented by the general formula (2) R ¹ R ² R ³ P (wherein R ¹ , R ² and R ³ have the same meanings as described above), and a general formula (3)

[0011]

[Chemical 3]

The bactericidal and algicidal agent of the present invention can be obtained by reacting with a benzyl halide represented by the formula (wherein R ⁴ has the same meaning as described above and X represents halogen). The reaction of the compounds of the above general formulas (2) and (3) is preferably carried out in the presence of a solvent at the reflux temperature of the solvent for 15 to 48 hours. Further, the benzyl halide is preferably used in an equimolar to 5-fold molar amount with respect to the trialkylphosphine.

Suitable organic solvents include n-hexane, n-heptane, n-octane, benzene, toluene, xylene and the like. The bactericidal algaecide according to the present invention,
If necessary, other fungicidal algaecides may be used in combination. 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, alkylpolyaminoethyleneglycine chloride, chlorine 1 or 2 of an organic antibacterial agent such as an organic agent and a silver-substituted zeolite, a silver-substituted abatite, etc.
You may use together more than one species.

Further, in the preparation, auxiliary agents such as a surface active agent, a binder, a colorant, a dispersant and a wetting agent may be blended, 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.

[0015]

The bactericidal / algicidal agent of the present invention exhibits a wide spectrum of activity effective against various bacteria, fungi, algae, and viruses, and particularly has excellent bactericidal activity against resistant Staphylococcus aureus (MRSA). It has a bactericidal effect and a growth inhibitory effect on bacteria, and an algaecidal effect on algae. Although the minimum bactericidal concentration (MIC) is not uniform depending on the type of benzylphosphonium salt, the type of preparation, various types of fungi, and the environment, the concentration of benzylphosphonium salt is exerted at 0.1 ppm or more, and the related phosphonium salt or The bactericidal activity is extremely higher than that of known quaternary ammonium salt-based bactericides. Moreover, the benzylphosphonium salt according to the present invention is more stable to heat than the quaternary ammonium salt and other organic compounds, for example, has a high decomposition temperature of around 350 ° C., and chemically. Is also stable.

[0016]

EXAMPLES The present invention will be further described below with reference to examples. Example 1 (p-ethylbenzyltrin-hexylphosphine
Synthesis of Fonium Chloride)
-Hexylphosphine (purity 95.60%) 111.19
g (0.37 mol) and 132.06 g of n-hexane are added and dissolved. Then 63.42 g (0.390 mol) of p-ethylbenzyl chloride (95.0%) are added. The reaction was carried out by stirring for 10 hours while refluxing the liquid temperature in the flask near the boiling temperature of n-hexane (70 to 75 ° C). The completion of the reaction was confirmed by a color reaction between unreacted tri-n-hexylphosphine and carbon disulfide. After completion of the reaction, the mixture was cooled to room temperature to precipitate crystals. The precipitated crystals were filtered, washed twice with n-hexane, filtered, and vacuum dried at room temperature (5 Torr, 5 hours).
As a result, 131.54 g of white crystalline p-ethylbenzyltri-n-hexylphosphonium chloride was obtained.
(Purity 96.9%) was obtained. The purity was measured by perchloric acid titration. To confirm the compound, ¹ H-NM
R, FAB / MASS. (Sample 1)

Examples 2 to 13 and Comparative Example 1 Examples except that various trialkylphosphines were used in place of tri-n-hexylphosphine in Example 1 and various benzyl chlorides were used in place of p-ethylbenzyl chloride. The benzylphosphonium salts of Examples 2 to 13 were prepared in the same manner as in 1. Obtained Examples 2 to
The benzylphosphonium salt of 13 and the compound of Comparative Example 1 are shown in Table 1. The compound used in Comparative Example 1 has the following formula (4)
It is shown in.

[0018]

[Chemical 4]

[0019]

[Table 1]

Test 1 (Bactericidal test against bacteria and filamentous fungi) The benzylphosphonium salts obtained in Examples 1 to 13 and the drug of Comparative Example 1 were tested for bactericidal activity. The types of strains used in the test, their test methods, and the results are shown below. (1) Test strains 7 types of bacteria and 2 types of filamentous fungi which are particularly harmful to industrial and hygiene were selected, and 9 types of strains shown below were tested. Bacterial Bs: Bacilius subtilis IFO 3007 (Bacillus subtilis) Ec: Escherichia coli NIHJ (E. coli) Pa: Pseudomonus aeruginosa IAM 1054 (Pseudomonas ^{aeruginosa) Sa 1: Staphylococcus aureus ATCC 6538p} ( Staphylococcus aureus) Sa ^2: Staphylococcus aureus (MRSA ) (Staphylococcus aureus) Ss: Shigella sonnei (Shigella) St: Salmonella typhimurium (S. typhimurium) Filamentous fungus An: Aspergillus niger ATCC 6275 (Black mold) Ps: Penicillius steckli IAM 7048 (Blue mold)

(2) Test method and its results (2-1) Test method The samples of Examples 1 to 13 and Comparative Example 1 were weighed accurately and 2
An aqueous solution of 00 μm / ml was prepared. Using this preparation, 200, 100, 50, 25, 10, 5,
Each sample was diluted to a concentration of 2.5 and 1 μm / ml to prepare a sample solution.
Next, 1 platinum loop of the test strain stored in the sample tube was ingested in 10 ml of a normal broth medium (three g of meat extract, 10 g of peptone and 5 g of sodium chloride dissolved in 1,000 ml of water), and shake-cultured at 30 ° C. for 48 hours. After doing, 20
The liquid stored at ℃ was used as the culture liquid 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 tube at 30 ° C for 30 minutes.
Let it work for a minute. After the action, add 1 ml of this solution to 100 parts of sterile water.
After being poured into a ml and uniformly diluted, 1 ml of this diluted solution was sampled to obtain 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) Bacteria culture Bacteria: 10 μl of the working solution was placed in a sterilized petri dish, and 15 ml of a culture medium for bacteria (Nissui Pharmaceutical Tryptosoya agar medium) was poured and solidified and cultured at 30 ° C. for 2 days. Filamentous fungus: 15 ml of filamentous fungus (potato dextrose agar medium from Nissui Pharmaceutical Co., Ltd.) was poured into a sterile petri dish to solidify, 10 μl of the working solution was added, and the mixture was cultured at 30 ° C. for 4 days. (2-3) Bactericidal Power Judgment Method and Results For the evaluation of the bactericidal power, colonies of each bacterium and filamentous fungus were observed with the naked eye, and those in which the medium was transparent and colonies could not be judged were killed. The lowest concentration of the sample liquid in which the bacterium was killed was defined as the minimum bactericidal concentration (MIC) of the compound,
The results are shown in Table 1.

Test 2 (Algicidal test against algae) The benzylphosphonium salts obtained in Examples 1 to 12 and the drug of Comparative Example 1 were subjected to an algicidal test. The types of algae used in the test, their test methods, and the results are shown below. (1) Test algae Green alga Chlorella vulagaris Cyanobacteria Oscillatoria chlorina (2) Test method and results The above green algae and cyanobacteria are inoculated in a Detmer medium and cultured in a climate machine at 25 ° C to obtain a test solution. Next, a 1/3 diluted solution of Detmer medium [Ca (NO ₂ ).
_{3 1.0g, KCl 0.25g, MgSO 4} · 7H 2 O
0.25g, KH ₂ PO ₄ 0.25g, FeCl ₃ 0.00
2 g / H ₂ O 3 L] and the chemical solution and the test solution are added so as to have a predetermined concentration, and the mixture is cultured in an artificial weather machine at 25 ° C. The culture is
Stir continuously 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 2 shows the minimum algicidal concentration of each drug.

[0024]

[Table 2]

[0025]

The bactericidal / algicidal agent according to the present invention exhibits a sufficient bactericidal / algicidal activity even if the concentration used is low, and is at least 0.1 p.
The effect is shown at a concentration of pm. Moreover, it is a bactericidal algaecide that has less foaminess as compared with conventional phosphonium salt compounds and quaternary ammonium salt compounds, has little foaming, and has little odor even when it is vigorously stirred such as in a cooling tower. . The bactericidal / algicidal agent of the present invention has bactericidal activity against resistant Staphylococcus aureus, which has recently been attracting attention as a nosocomial infectious agent, and therefore provides an effective means as a countermeasure. Further, it can be widely applied not only to other medical purposes but also to industrial fields, process water for producing pulp and paper, agricultural fields, and food manufacturing fields.

 ─────────────────────────────────────────────────── ─── Continuation of front page (72) Inventor Seiji Shimura 9-15-1, Kameido, Koto-ku, Tokyo Nippon Kagaku Kogyo Co., Ltd. Research & Development Division (72) Inventor Kazunori Tanaka Shiooka Prefecture Iwata-gun Shiota Nitta Hamano No. 328 Kai Kasei Co., Ltd. (72) Inventor Koichi Iwabuchi Shiooka Prefecture Iwata-gun Fukuda-cho Shio Nitta Hamano No. 328 Kai Kasei Co., Ltd. (72) Inventor Yoshihiro Konagai Iwata-gun Shizuoka Fukuda Town Shio Shinhama No. 328 KAI Kasei Co., Ltd.

Claims (2)

[Claims] 1. The following general formula (1): (In the formulas, R ¹ , R ² and R ³ are a substituted or unsubstituted alkyl group having 1 to 22 carbon atoms, R ⁴ is a hydrogen atom, a hydroxyl group, a nitro group, an alkyl group having 1 to 4 carbon atoms. Or halogen, X ⁻ represents an anion of an inorganic acid or an organic acid), which is a bactericidal and algicidal agent containing a benzylphosphonium salt represented by the formula: 2. The bactericidal / algicidal agent according to claim 1, wherein the anion in the general formula (1) is a halogen ion.