JPH0459282B2 - - Google Patents

Description

[Detailed description of the invention]

(Industrial Application Field) The present invention relates to a novel polybasic acid amine salt type disinfectant. (Prior art and problems to be solved by the invention) Many disinfectants have been known in the past, such as chlorine compounds, phenol compounds, aldehydes, acids, esters, quaternary ammonium salts, and antistatic substances, and are used in a wide variety of fields. has been done. However, these are generally only effective against specific types of microorganisms, the stronger their bactericidal power, the more toxic or irritating they are, or they only dissolve in specific solvents, making them inconvenient to use. do not have. In addition, there are many fatty acids, ranging from short-chain to long-chain, that have bactericidal and antifungal effects, although they are not extremely strong, and many of them are generally of low toxicity and are used in foods and medicines. These are often used as alkali metal salts due to their solubility, but their bactericidal activity is often slightly reduced. (Means for Solving the Problem) As a result of intensive research to overcome the drawbacks of such conventional disinfectants, the present inventors have developed an amine salt of a polybasic acid represented by the general formula () below. The inventors have discovered that the compound has a wide range of solubility, exhibits strong bactericidal activity against various bacteria, and has low toxicity and low irritation, and based on this knowledge, the present invention was developed. That is, the present invention provides the general formula (In the formula, n and n' represent numbers from 4 to 10, X represents a hydrogen atom or -COOZ, and Z represents a hydrogen atom, a lower alkyl group, an alkyl group having 1 to 18 carbon atoms, or a carbon number 1 to 12 at least one alkylol group of
At least one of Z is the ammonium ion. ) The present invention provides a disinfectant characterized by containing an amine salt of tetra or pentacarboxylic acid represented by the following as an active ingredient. The amine salt of the tetra or pentacarboxylic acid represented by the general formula (), which is the active ingredient of the disinfectant of the present invention, can be obtained by neutralizing the acid of the following general formula () with a predetermined amine in a conventional manner. can be manufactured. (In the formula, n and n' have the same meanings as above. Y
represents a hydrogen atom or COOH. ) Conventionally, well-known polycarboxylic acids generally have short molecular chains, or are linear dicarboxylic acids based on a structure in which carboxyl groups are bonded to both ends of the molecular chain, that is, carbons at the α and ω positions. Many of them were considered to be derivatives of. However, the tetra or pentacarboxylic acid represented by the above general formula () has a carboxyl group at one end of its molecular chain, that is, at the α-position carbon,
The other end is an alkyl group and the other carboxyl group is a polycarboxylic acid bonded to the middle carbon of the molecular chain. Therefore, it is a unique polycarboxylic acid that is considered to be a derivative of a normal linear monobasic acid. These polycarboxylic acids can be produced by using a fatty acid derivative having a cyclohexene ring as a raw material and treating it with various known oxidation methods. When neutralizing the acid of general formula () above, the amine used for neutralization becomes ammonium ion,
At least one of -COOZ forms an amine salt in the form of -COO ^- NR ₃ H ⁺ (NR ₃ represents an amine having at least one of the alkyl group or alkylol group). The amine (NR ₃ ) used here is selected from alkylamine and alkanolamine as described above, the alkylamine may be mono-, di-, or trialkylamine, and the alkanolamine is mono-, di-, or trialkylamine. Either is fine. More specifically, an alkylamine is represented by NR′ ₃ , where R′ is a hydrogen atom or a straight-chain or branched alkyl group having 1 to 18 carbon atoms;
R's may be the same or different, but at least one is the alkyl group described above. Alkanolamines are represented by the general formula _NR''3 , where R'' is a hydrogen atom, an alkylol group having 1 to 12 carbon atoms, or an alkyl group having 1 to 18 carbon atoms, and R'' may be the same or different. It may be on, but
At least one is an alkylol group. Examples of such alkylamines are N-methylamine, N-oleylamine, N-dodecylamine, N-isooctadecylamine, N,N-
dihexylamine, N-methyldecylamine,
Includes N,N,N-trihexylamine and the like. Examples of alkanolamines include monoethanolamine, triethanolamine, N,N-diisopropylethanolamine, decanolamine, and the like. In the general formula (), the lower alkyl group of Z refers to an alkyl group having 1 to 4 carbon atoms. The disinfectant of the present invention can be applied to various uses by preparing a salt of a tetra or pentacarboxylic acid represented by the general formula (), for example, in an aqueous solution, and usually has a concentration of 0.0005 to 2.0% by weight, preferably It is used as an aqueous solution of 0.01-1.0% by weight. In the present invention, one or more Z in the compound of the general formula () is an amine salt. The more amine salts with many carbon atoms and fewer hydroxyl groups in Z, the more
Furthermore, the greater the number of alkyl groups and the greater the number of carbon atoms, the more oil-soluble the compound of general formula () becomes. Further, in the compound of the general formula (), highly saturated salts with alkyl amines consisting of alkyl groups having a low number of carbon atoms have low antibacterial activity, but can be used as preservatives with low toxicity. The more free carboxyl groups (i.e., when Z is a hydrogen atom), the higher the pH of the aqueous solution.
decreases. Therefore, the pH of the compound itself can be adjusted depending on the purpose. (Effects of the Invention) The pentacarboxylic acid amine salt and tetracarboxylic acid amine salt according to the present invention can be made into compounds with various structures to be dissolved in various solvents, and each compound has a wide range of solubility. Low foaming and convenient to use. Furthermore, although they are anionic, they are amine salts and exhibit strong antibacterial activity against various bacteria, yeast, etc., and have the excellent effects of being low toxicity and low irritation. Note that when comparing the pentacarboxylic acid amine salt and the tetracarboxylic acid amine salt, there is no significant difference in terms of action and effect, and the former is either equivalent or slightly superior. (Examples) Next, the present invention will be described in more detail based on Examples and Reference Examples. Note that some of the amine salts of tetra- or pentacarboxylic acids used in the examples were synthesized from amines and tetra- or pentacarboxylic acids obtained from saturated sodium salts prepared according to Reference Examples 1 to 3 below. The same acid and the corresponding amine (special grade reagent or rectified product) were used in Example 4).
A 20% ethanol solution is mixed stoichiometrically, depending on the case, either as is (1) or after distilling off the ethanol under a vapor pressure (vacuum degree and temperature control) that is sufficiently higher than the vapor pressure of the amine (2). It was used for measurement as an aqueous solution with a predetermined concentration. (1) is the case when diluted with water to a fairly low concentration and no effect of ethanol appears, and (2) is the opposite case. In addition, it was confirmed for representative examples that the results obtained by these methods and the results obtained using the synthetic product were in agreement. In addition, the raw materials used in the reference example are the following general formula (A) and
It is a fatty acid derivative having a cyclohexene ring having the structure (B), and n, n', R, R', etc. in the formula are shown respectively in the description of reference examples. (R, R': H or alkyl group) The bactericidal activity test method is as explained below. Reference example 1 Raw material B (n=5, n'=7, CH ₃ together with R and R')
3.01 g of glacial acetic acid and 30 ml of glacial acetic acid were each weighed into 50 ml pear-shaped three-necked flasks. The flask has a gas blowing tube,
A cooler and a stirrer were installed. The reaction takes place in a flask of 10~
The solution was placed in a constant temperature bath at 14°C, and ozone-oxygen mixed gas (ozone concentration approximately 3 wt%) was blown into the solution for 38 minutes while stirring to effect ozonation. After ozonation, add 0.02g of manganese acetate [Mn(CH ₃ CO ₂ ) _{2.4H 2} O], raise the temperature to 80℃ while stirring, and at 80℃
Ozonide was decomposed and oxidized by blowing oxygen gas (flow rate 270 ml/min) for 1.5 hours. After the reaction, the reaction solution was filtered to remove the manganese compound, the acetic acid was then distilled off, the reaction product was collected with ether and washed with water, and the ether was distilled off to obtain 31.8 g of the reaction product (yield 90.3%). Ta. This reaction product gave the following analytical values. That is, acid value: 244.6 (theoretical value: 252.4), IR spectrum (cm ^-1 ): 2500-2700 (carboxyl group), 1710
(carbonyl group), ¹ H-NMR spectrum (ppm):
0.9 (terminal methyl group), 1.2-1.3 (methylene group), 3.4
(methyl ester group), 8.5-8.6 (carboxyl group), ¹³ C-NMR spectrum (ppm): 14.3 (terminal methyl group), 23.0-35.5 (methylene group), 40 (methyl ester group), 174.2-181.1 (carboxyl basis). From these analysis results, it was confirmed that the reaction product was tetracarboxylic acid dimethyl ester having the following structure. Reference example 2 Raw material A (n=5, n'=7, R and R' both CH ₃ )
10.03 g of glacial acetic acid and 80 ml of glacial acetic acid were each weighed into 100 ml pear-shaped three-necked flasks. The flask was equipped with a gas blowing tube, a condenser, and a stirrer. For the reaction, place the flask in a constant temperature bath at 10 to 13℃ and stir the solution while adding ozone-oxygen mixed gas (ozone concentration approximately 3.5wt%).
was blown at a flow rate of 210 ml/min for 80 minutes to effect ozonation.
After ozonation, manganese acetate [Mn(CH ₃ CO ₂ ) ₂ .
4H ₂ O] was added, the temperature of the reaction solution was raised to 80°C while stirring, and oxygen gas (flow rate 210ml/min) was blown at 80°C for 3 hours to perform oxidative decomposition of ozonide. After the reaction, the reaction solution was filtered to remove manganese compounds, then acetic acid was distilled off, and the reaction product was extracted with ether and washed with water to obtain 10.33g of reaction product.
I got it. Various analyzes were conducted on this reaction product and the following results were obtained. Neutralization value: 218.8 _-1 (theoretical value 223.3), IR spectrum (cm): 2500-2700 (carboxyl group), 1710 (carbonyl group), ¹ H-NMR spectrum (ppm): 0.88
(terminal methyl group), 1.3 (methylene group), 3.65 (methyl ester group), 3.08 (carboxyl group), ¹³ C-NMR
Spectrum (ppm): 14.0 (terminal methyl group), 22.4-34.1 (methylene group),
51.5-52.0 (methyl ester group), 171.8-178.4 (carbonyl group) From these analysis results, it was confirmed that the reaction product was pentacarboxylic acid trimethyl ester having the following structure. Reference Example 3 3.67 g of pentacarboxylic acid trimethyl ester obtained in Reference Example 2 was dissolved in 50 ml of ethanol, and 70 ml of a 2% aqueous solution of sodium hydroxide was added thereto.
The reaction was carried out at 80-85°C for 2 hours. After the reaction, the reaction solution was evaporated and concentrated, 5 to 10 ml of water was added thereto, the total volume was made up to about 200 ml with methanol, and the precipitated inorganic salt was filtered off. Next, about 50 ml of ether was added to the filtrate, and the precipitated liquid was filtered off. Water/
The product was purified by reprecipitation several times with a mixed solution of methanol/ether (1:20:5) to obtain 3.8 g of white crystals. The spectral data of this product is shown below. IR spectrum (cm ^-1 ): 1570 (carboxylate ion) ¹ H-NMR spectrum (δ): 1.32 (terminal methyl) 1.70 (methylene) ¹³ C-NMR spectrum (ppm): 14.5 (terminal methyl) 22.6-38.5 ( methylene) 51.7 (methine) 167.7-1847 (carbonyl) From these analysis results, the reaction products are 1,9,
It was confirmed to be pentasodium 10,11,12-octadecanepentacarboxylate (). Reference Example 4 6.0 g of 0.300 g of 1,9,10,11,12-octadecanepentacarboxylic acid obtained by hydrolyzing the pentabasic acid pentasodium salt obtained in Reference Example 3 with hydrochloric acid and partitioning with ethyl ether. Monoethanolamine (bp ₁₂ 70.5-71.5°C) dissolved in ethanol
When 0.239g (1.2 times the theoretical amount as saturated salt) is added and stirred, it generates heat and reacts. After stirring at about 45℃ for 1 hour, activated charcoal was added to the slightly pale yellow solution.
0.1 g was added, stirred for an additional 2 hours, filtered under suction, and the filtrate was dried at about 50° C./50 mmHg to obtain a slightly pale yellow solid. This was thoroughly washed with about 20 ml of benzene and dried under vacuum at about 50°C/30 mmHg to produce a slightly pale yellow solid of 1,9,10,11,12-octadecanepentacarboxylic acid pentamonoethanolamine [C ₁₇ C ₅ (MEA) ₅ ] was obtained. Elemental analysis values are 50.46% carbon, 9.01% hydrogen, 8.90% nitrogen (theoretical amount,
(C: 50.18%, H: 9.34%, N: 9.14%) Next, the antibacterial activity test method adopted in Example 2 and below will be described. (1) Put 3 g of sample aqueous solutions of various concentrations and 80 mg of agar medium (Far East standard medium; yeast extract - peptone, glucose, agar) into a test tube with a lid (12 x 65 mm), heat to dissolve at about 80℃, and then tilt. Cool and leave it outside for about 1 hour after solidifying, then cover it loosely.
It was left at 38°C for 5 days, and the growth state of airborne bacteria was observed. (Note) -: No colonies occur at all: Same as above, minimum inhibitory concentration ⊥: Slight occurrence +: Moderate occurrence: Significant occurrence: Occurrence all over the surface (2) Bacteria for inoculation on a plate medium to which the sample has been added at an arbitrary concentration After the solution was smeared and cultured, the lowest concentration at which growth was inhibited was defined as the minimum inhibitory concentration. In the case of mold, potato dextrose agar medium was used as a medium and cultured at 25°C for 7 days, and for yeast, YM agar medium was used and cultured at 25°C for 2 days. This test was conducted at the request of the Japan Food Research Institute. Example 1 Minimum inhibitory concentration (MIC) of monoethanolamine (MEA) salts of 1,9,10,11,12-octadecanepentacarboxylic acid (hereinafter abbreviated as pentacarboxylic acid) with different degrees of neutralization against airborne bacteria and,
Some results for M.flavas are shown in Figure 1. In FIG. 1, the horizontal axis indicates the number of free carboxyl groups in pentacarboxylic acid or the number of MEA. Saturated salts (in the general formula (), all Z's are amine salts) and free acids have weak antibacterial activity, but unsaturated salts decrease the MIC, and a maximum is shown at 1 mol salt.
It is quite strong at 200ppm for a low toxicity substance. The MIC of the same salt against M.flavas was 400 ppm. Example 2 FIG. 2 shows the tendency of the alkyl chain length of MIC against airborne bacteria for mono- and tetraalkylamine salts of pentacarboxylic acid. In the figure, the horizontal axis shows the chain length of the alkylamine, the solid line shows the case where one amine is introduced, and the broken line shows the case where three amines are introduced. As is clear from this figure, the number of carbon atoms is around 12 in both cases of 1 mole and 3 moles of amine.
The maximum of was observed. Example 3 FIG. 3 shows trends regarding the neutralization mole number (x) of MIC against airborne bacteria for dodecylamine and cetylamine salts of pentacarboxylic acid. As is clear from this figure, a neutralization mole number of 2 to 3 shows the strongest tendency. Example 4 FIG. 4 shows trends regarding the MEA neutralization mole number (y) of unneutralized carboxyl for the dodecylamine salt of pentacarboxylic acid. As is clear from this figure, as the amount of dodecylamine increases, the maximum value occurs on the side with less MEA. Example 5 Monoethanolamine salt of pentacarboxylic acid,
Table 1 shows the MICs of oleylamine salt and dodecylamine salt against airborne bacteria and various bacteria. For monoethanolamine, a lower degree of neutralization was better, and the longer the substituted amine chain was, the better it was, and the 2-mole salt of dodecylamine was extremely effective against M.flavas, B.subtilis, etc.

【table】

[Table] Example 6 3 g of tetracarboxylic acid dimethyl ester obtained in Reference Example 1 was dissolved in 40 ml of ethyl alcohol,
Add 55g of 2% aqueous solution of sodium hydroxide and
Neutralization and saponification reactions were carried out for 2 hours. then 5
After hydrolyzing with 25g of % hydrochloric acid aqueous solution, partitioning with ethyl ether and drying, 1,9,10,
2.5 g of 11,12-octadecanetetracarboxylic acid was obtained. This was prepared using the same method as in Examples 1 and 2.
It was neutralized with amine and the MIC against airborne bacteria was measured. The results are shown in Table 2. Monooctylamine salt (C ₁₇ C ₄ H ₄ (8N)) is
100 ppm, and 20 ppm for dodecylamine salt (C ₁₇ C ₄ H ₂ (12N) ₂ ), which is almost the same result as in the case of pentacarboxylate.

【table】 [Brief explanation of the drawing]

FIG. 1 shows the relationship between the number of neutralized moles of the pentacarboxylic acid monoethanolamine salt of Example 1 and the antibacterial activity. FIG. 2 shows the relationship between the alkyl chain length of the amine and the antibacterial activity of the pentacarboxylic acid alkanolamine salt of Example 2. FIG. 3 shows the relationship between the number of neutralized moles of the pentacarboxylic acid long-chain amine salt of Example 3 and the antibacterial activity. FIG. 4 shows the relationship between the MEA neutralization mole number and the antibacterial activity of the pentacarboxylic acid dodecylamine salt of Example 4.

Claims (1)

[Claims] 1. General formula (In the formula, n and n' represent numbers from 4 to 10, X represents a hydrogen atom or -COOZ, and Z represents a hydrogen atom, a lower alkyl group, an alkyl group having 1 to 18 carbon atoms, or a carbon number 1 to 12 at least one alkylol group of
At least one of Z is the ammonium ion. ) A disinfectant characterized by containing an amine salt of tetra or pentacarboxylic acid as an active ingredient.