JP2008163011A - Germicidal compound and germicidal composition - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To provide a germicidal compound having germicidal properties comparable to those of conventional germicidal compounds, having high safety and being readily handleable. <P>SOLUTION: The germicidal compound is an N-alkyl-modified phenylimidazole compound in which carbon number of the alkyl group is ≥5, preferably 6-12. <P>COPYRIGHT: (C)2008,JPO&INPIT

Description

  The present invention relates to a bactericidal compound that is highly safe and easy to handle, and a bactericidal composition containing the bactericidal compound.

  Traditionally, industrial products such as paints, adhesives, starch pastes, glue, synthetic rubber latex, cement admixtures, etc., are prone to the growth of microorganisms such as bacteria, mold, yeast, etc. It has become. In order to control this, bactericides such as preservatives and fungicides are used. Various compounds are known as bactericides. Among them, isothiazoline compounds are particularly widely used in various industrial fields because they have a broad antibacterial spectrum. For example, Patent Document 1 describes an industrial bactericidal composition containing a thiophene compound and an isothiazoline compound.

  However, the isothiazoline compound has a mechanism in which a reactive species produced by cleavage of the isothiazoline ring exhibits bactericidal properties by binding to a protein or the like. As a result, workers who often handle this may cause an allergic reaction to the skin.

  The present invention has been made in view of such problems, and aims to provide a bactericidal compound that has bactericidal properties comparable to conventional products, is highly safe, and is easy to handle. is there.

JP 200355110 A

  As a result of intensive studies to achieve the above object, the present inventor is effective to use a compound in which phenylimidazole is used as a base and the N-position (position 1) is modified with an alkyl group having a specific chain length as a bactericidal component. As a result, the present invention has been completed.

That is, the present invention has the following characteristics.
1. A bactericidal compound, which is an N-alkyl modified product of a phenylimidazole compound, wherein the alkyl group has 5 or more carbon atoms.
2. Claim | item 1 whose carbon number of the said alkyl group is 6-12. The bactericidal compound as described.
3. Item 1. Or item 2. A bactericidal composition comprising the described bactericidal compound as an active ingredient.

  The bactericidal compound of the present invention can exhibit bactericidal properties comparable to conventional products. Moreover, the bactericidal compound of the present invention is highly safe, hardly causes skin irritation, and is easy to handle.

  Hereinafter, the best mode for carrying out the present invention will be described.

  The bactericidal compound of the present invention is an N-alkyl modified product of a phenylimidazole compound, and is a compound in which the alkyl group has 5 or more carbon atoms. Such a compound of the present invention exhibits excellent bactericidal properties, is highly safe, and is easy to handle.

  The compound that is the base of the bactericidal compound of the present invention is a phenylimidazole compound. Such a compound has a phenyl group in the imidazole ring, and in the present invention, a compound having a phenyl group at the 2-position of the imidazole ring as shown in [Chemical Formula 1] is particularly preferable. In addition, as long as the effect of this invention is not inhibited, what has a substituent in a part of imidazole ring and / or a phenyl group can also be used.

  As shown in [Chemical Formula 2], the bactericidal compound of the present invention has an alkyl group (—R) having 5 or more carbon atoms at the N-position (1-position) of the phenylimidazole compound.

Compounds that are not alkyl-modified at the N-position (position 1) have little hydrophobic interaction with phospholipids in the cell membrane of microorganisms, or are not recognized as substrates by enzymes in the cells, so enzyme inhibition does not occur A sufficient bactericidal property cannot be obtained.
Moreover, when the carbon number of the alkyl group is less than 5, satisfactory performance in bactericidal properties cannot be obtained. In the present invention, it is essential that the alkyl group has 5 or more carbon atoms, preferably 6 to 12, more preferably 7 to 10, and further preferably 7 to 9. If the carbon number of the alkyl group is within such a range, a stable bactericidal effect can be expressed against a wider variety of microorganisms.
The alkyl group may be either a linear alkyl group or a branched alkyl group, but a linear alkyl group is preferred in the present invention.

  The bactericidal compound of the present invention can be produced by N-alkylation of a phenylimidazole compound. For example, phenylimidazole is dissolved in an aprotic polar solvent, alkali is added, and heating is started. When phenylimidazole is deprotonated, an alkyl compound having a leaving group at the 1-position carbon is dropped, and after completion of the dropping, the reaction is carried out for about 5 hours while refluxing. After stopping the reaction, the produced salt is removed, and the solvent is further removed by distillation, whereby the target compound for crude purification can be produced. Further, the target compound with high purity can be obtained by purification by a known method.

The bactericidal compound of the present invention may exist as a salt. If the bactericidal compound of the present invention is a salt, it can improve solubility in water, improve crystallinity, etc., and is effective in formulating the compound into various forms such as aqueous solutions, powders, and granules. is there. It is also possible to increase the solubility of the compound within the optimum pH range of 2 to 8.5 such as mold.
In addition, when the compound of the present invention is used as a salt, it is considered that a proton is coordinated to an unshared electron pair on the nitrogen atom of the imidazole ring, and the molecule becomes positively charged. When many of the compounds are present as cations, the interaction with phospholipids and proteins constituting microorganisms is increased, and the bactericidal effect can be expected to be improved.
Such a salt can be represented by the structure shown in [Chemical Formula 3]. X ⁿ⁻ is an organic or inorganic anionic group, and n is an integer.

Examples of the acid that gives an organic anionic group include acetic acid, adipic acid, ascorbic acid, benzoic acid, benzenesulfonic acid, butyric acid, camphoric acid, camphorsulfonic acid, citric acid, cyclohexylsulfamic acid, ethanesulfonic acid, fumaric acid, Glutamic acid, 2-hydroxyethylsulfonic acid, heptanoic acid, hexanoic acid, hydroxymaleic acid, lactic acid, malic acid, maleic acid, methanesulfonic acid, 2-naphthalenesulfonic acid, succinic acid, pamoic acid, phenylacetic acid, pivalic acid, propionic acid , Salicylic acid, stearic acid, succinic acid, tartaric acid, tosylic acid, undecanoic acid, aspartic acid and the like. Examples of the acid that gives an inorganic anionic group include hydrochloric acid, sulfuric acid, nitric acid, bicarbonate, bisulfuric acid, hydrobromic acid, persulfuric acid, phosphoric acid, diphosphoric acid, and hydroiodic acid.

Among the salts obtained by these acids, pharmaceutically acceptable methanesulfonate, ethanesulfonate, benzenesulfonate, tosylate, oxalate, tartrate, citrate, maleate, succinate Acid salt, acetate salt, benzoate salt, ascorbate salt, lactate salt, apple trisalt salt, glutamate salt, aspartate salt, hydrochloride salt, hydrobromide salt, hydroiodide salt salt, phosphate salt, sulfate salt Nitrate or the like increases safety. In particular, among these, hydrochloride, hydrobromide, phosphate, sulfate, methanesulfonate, tosylate, oxalate, tartrate, citrate, acetate, lactate, glutamate, asparagine Acid salts and the like are preferred.
Such salts can be synthesized by conventional chemical synthesis methods. Specifically, it can be synthesized by a method of reacting 1 equivalent or more of an acid and an imidazole compound in water or an organic solvent or a mixed solvent thereof. At this time, excess acid may be removed under vacuum, or an anion group may be exchanged using an ion exchange resin.

  The bactericidal compound of the present invention may be used in a form corresponding to the intended application, for example, the compound itself can be used as it is, or used as a bactericidal composition containing the compound as an active ingredient. You can also. When the compound of the present invention is used as a bactericidal composition, the form thereof is a form in which the bactericidal compound is dissolved, dispersed or emulsified in a medium, or a form in which bactericidal compounds, binders, other additives, etc. are appropriately mixed. Etc.

  Examples of the medium include water, alcohols, glycols, glycol ethers and the like. Examples of the binder include inorganic binders such as cement, gypsum, and water glass, and organic binders such as vinyl acetate resin, epoxy resin, acrylic resin, urethane resin, acrylic silicon resin, and fluorine resin. The bactericidal composition containing such a binder can be used as a paint, and can also be used as a composition for a molded article such as a sheet material. Examples of additives include pigments, aggregates, fibers, film-forming aids, plasticizers, antifreeze agents, antiseptics, antifungal agents, antifoaming agents, thickeners, leveling agents, pH adjusters, and pigment dispersions. Agents, anti-settling agents, anti-sagging agents, matting agents, ultraviolet absorbers, light stabilizers, antioxidants, adsorbents, crosslinking agents, catalysts and the like.

  What is necessary is just to set the compounding quantity of the bactericidal compound in a bactericidal composition suitably. When the bactericidal composition is used as a paint or the like, the ratio of the bactericidal compound in the bactericidal composition is usually about 10 to 5000 ppm (preferably 100 to 2000 ppm).

  Examples are given below to clarify the features of the present invention.

(Synthesis method)
20 mmol of phenylimidazole was dissolved in 30 ml of DMF (N, N-dimethylformamide), 30 mmol of sodium methoxide was further added, and the mixture was stirred with heating under a nitrogen atmosphere. After a change in the color of the solution was observed, 40 mmol of alkyl bromide was added dropwise and stirred for 5 hours while refluxing. After stopping the reaction, the reaction solution was filtered to remove the precipitate, and then the solvent was distilled off under reduced pressure. The residue is purified by silica gel column chromatography (dichloromethane: methanol = 20: 1), and the fraction in which the spot appears at Rf = 0.6 to 0.8 by TLC (dichloromethane: methanol = 10: 1). Collected and concentrated to obtain the bactericidal compound shown in [Chemical Formula 2].

  In addition, as alkyl bromide, what has a C4-C12 linear alkyl was prepared, and eight types of bactericidal compounds were manufactured with the said synthesis method using each alkyl bromide.

(Test method)
The following tests were conducted on the eight bactericidal compounds obtained by the above method and OIT (2-octyl-4-isothiazolin-3-one) to evaluate the bactericidal properties.

A test solution in which each bactericidal compound was dissolved in ethanol so as to be 4 mg / ml was prepared, and 0.1 ml of this was dropped on a filter paper cut into 30 mm × 30 mm. This was air-dried to obtain a test piece.
The said test piece was left still in the center of the potato dextrose agar plate culture medium which added chloramphenicol. Next, 50 ml of dioctyl sodium sulphosuccinate was added to distilled water, 5 mold spores were added to autoclaved sterilized water, and 1 ml of the spore suspension filtered with gauze was dropped into the agar medium at 28 ° C. Culture was performed for 1 week in the set incubator. As the mold spores, those shown in Table 1 were used.

The state after culture was confirmed and evaluated according to the following criteria. The results are shown in Table 2.
A: No hyphal extension is observed on the test piece. O: Hypha extension is observed in less than 1/3 of the test piece. Δ: Hypha extension is observed in 1/3 or more and less than 2/3 of the test piece. Mycelial elongation is observed in more than 2/3 of the specimens

Claims (3)

  A bactericidal compound, which is an N-alkyl modified product of a phenylimidazole compound, wherein the alkyl group has 5 or more carbon atoms.   The bactericidal compound according to claim 1, wherein the alkyl group has 6 to 12 carbon atoms.   A bactericidal composition comprising the bactericidal compound according to claim 1 or 2 as an active ingredient.