JPS5953898B2 - Aliphatic compounds with sulfinyl or sulfonyl groups - Google Patents

Description

[Detailed description of the invention] The present invention relates to novel compounds with antibacterial activity.

More specifically, it relates to allyl alcohol or acrylic acid derivatives having a sulfinyl group or sulfonyl group at the β position. There are various problems when using various existing antimicrobial agents.

That is, existing antimicrobial agents are applicable to a very narrow range of systems. Therefore, currently, in selecting existing antimicrobial agents for a target system, a large number of agents must be subjected to numerous tests. Although phenolic antimicrobial agents are widely used, they generally have a narrow antimicrobial spectrum and must be used at high concentrations. Halogen-substituted aromatic antimicrobial agents are also widely used, but they tend to accumulate without being decomposed in nature, which can cause problems. Other antimicrobial soaps are also known to exhibit significant antimicrobial activity at low concentrations, making it difficult to apply them to systems where it is desired to avoid foaming or to anionic emulsion systems because they form insoluble complexes. In order to solve these problems, the present invention was completed as a result of intensive research. An object of the present invention is to provide a compound having antibacterial activity that can be used in a wide variety of applications.

The present invention provides a compound represented by the following general formula (1). RSOn-CH=CHX (1) [In the formula, R represents an alkyl group, alkenyl group or aryl group having 1 to 20 carbon atoms.

X is CH2OH or COYO, where Y is a hydroxyl group or its alkali metal, alkaline earth metal or NH4 salt, an alkoxy group having an alkyl group having 1 to 20 carbon atoms, an alkoxyethoxy group or an alkoxypolyethenoxy group, intramolecular or An alkoxyl group or N formed by removing H from one 0H group of a polyhydric alcohol which may have an ether bond resulting from intermolecular dehydration.
R'R'' (where R' is a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, or a hydroxyalkyl group having 2 to 6 carbon atoms, and RI is a hydrogen atom, a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, 2 to 6 substituted with an alkyl group or a hydroxyl group or a sulfonic acid group in the form of a salt
) is an alkyl group. n is 1 or 2.
] The compound represented by the general formula (1) is obtained by oxidizing the compound represented by the general formula (2) with an inorganic or organic peroxide. X is as described above.

) Examples of the inorganic peroxide used here include hydrogen peroxide and sodium metaperiodate.

Examples of organic peroxides include metachloroperbenzoic acid, perbenzoic acid, and peracetic acid. The amount of peroxide used varies depending on the oxidation state of sulfur in the compound of general formula (1), and when n=1, the amount of peroxide used is about 1.1 to 1.5 per Two times the molar amount is allowed, and in the case of n=2, about 2 to 4 times the molar amount is allowed.

The solvent and reaction time used during the reaction depend on the type of oxidizing agent used, but generally, the reaction time is 10°C to 80°C in a hydrous alcohol, acetic acid, or a chlorinated hydrocarbon solvent such as chloroform or methylene chloride. The reaction is carried out in the °C range.

Specifically, when sodium metaperiodate is used, the temperature is 0 to 25°C in aqueous alcohol, when hydrogen peroxide is used, it is 60 to 70°C in aqueous alcohol, and 30 to 80°C in acetic acid. When using benzoic acid, 0 to 25% in chlorinated hydrocarbons such as chloroform or methylene chloride.
C, and when peracetic acid is used, the reaction is carried out at -10 to 0 C. The compound represented by the general formula (2), which is a raw material for the compound of the present invention (formula 1), has the general formula (3) RS-H
(3) (in the formula, R is as described above)
The mercaptan represented by the formula (3) is reacted with propargyl alcohol in the presence of a base catalyst, or the general formula (3)
Compound (4) RS-CH=CH-COOM (4) obtained by reacting mercaptan represented by and acetylene monocarboxylic acid in an aqueous solution of alkali metal hydroxide
) (In the formula, R is the same as above, and M is hydrogen or an alkali metal.

) and further esterified or amidated by a conventional method.

All of these compounds were synthesized for the first time by the present inventors, and a separate application is currently being filed. In the compound represented by the general formula (2) which is the starting material in the method of the present invention, one of the groups represented by Y is a polyhydric alcohol which may have an ether bond formed by intramolecular or intermolecular dehydration. Examples of alkoxy groups formed by removing H from 0H groups include ethylene glycol, propylene glycol, glycerin, erythritol, pentaerythritol, xylitol, sorbitol, and mannitol, as well as diglycerin, dipentaerythritol, xylitane, zorbitan, mannitan, and polyethylene. Refers to an alkoxy group formed by removing H from one OH group of a polyhydric alcohol such as glycol.

The compound represented by the general formula (1) of the present invention is used as a non-medical sterilizer, disinfectant, or a fungicide or preservative.

Gram-stain-positive bacteria such as Staphylococcus and Bacillus subtilis, which are typical microorganisms that cause various microbial disorders in the living environment, Escherichia coli and Proteus bacteria, and Pseudomonas bacteria such as Pseudomonas aeruginosa, which is famous as a putrid bacterium. It also inhibits the growth of Gram stain-negative bacteria such as Penicillium, Asperigillus, Sorzopus, and other molds, and is also effective against yeasts of the genus Candida that cause candidiasis. The physicochemical properties and antimicrobial activity of the substance of the present invention can be changed by changing RJ in general formula (1), so it is possible to select and add a substance with the most suitable structure for the system to which it is applied. , it was possible to overcome the drawbacks of conventional antimicrobial agents, which have antimicrobial properties but cannot be used due to poor compatibility with systems.

Since the substance of the present invention has the above-mentioned properties, it can be used, for example, in various emulsion-type cutting oils, cleaning soaps,
It can be added to jump products, conditioners, hair treatments, emulsions, cosmetics, textile finishing agents, textile oils, paints, printing inks, etc.

Reference example 1 C12H2,S-CH: CH-CH2OH and CH2
Synthesis of =C(SCl2H25)CH2OH ethanol (
41) Dissolve metallic sodium (5.09 atoms).

Lauryl mercaptan (5.0 mol) was added dropwise to the solution at room temperature. Then, propargyl alcohol (6.5 mol) was added while cooling on ice. The reaction mixture was heated at 70°C.
After heating and stirring for 1 hour, the mixture was poured into water and extracted with benzene. A mixture of alcohol I (3-laurylmercapto-2-propenol) and alcohol (2-laurylmercapto-2-propenol) is obtained with an isolated yield of 84% (based on mercaptan). The production ratio of alcohol summer and H is 1:0.86. Alcohol I can be separated using a silica gel column. Alcohol I (R=dodecyl) Melting point 50-51℃ (from hexane) IR (KBr) 3300,1050cm-1NFVR
(CCl4, TMS, 6OMH2) δ 4.05 (Su, 2H, allylic methylene), 5.38-5.95pp
1 (nl!, 2H, Olefin) Elemental Analysis Values From the analysis results, it was confirmed that the above crystalline substance had the following structural formula.

C,,H25S-CH=CH-CH2OH alcohol l
(R=dodecyl) Melting point 42-43℃ (from hexane) IR (KBr) 3300,1030CIIL-1NM
R(CCl,,TMS,6OMH2)δ 408(Br
Oads, 2H, allylic methylene), 5.38-5.
95 Purchase (nl!, 2H, Olefin) Elemental analysis value From this analysis result, it was confirmed that the above crystalline substance had the following structural formula. Reference Example 2 Synthesis of β-laurylsulfenyl acrylic acid Caustic soda (0.50 mol) in water (500 ml).

Acetylene monocarboxylic acid (0.55 mol) was added dropwise thereto.

Then lauryl mercaptan (0.50 mol) was added at room temperature.
Add. After completion of the dropwise addition, the mixture was stirred at room temperature for 3 hours. The reaction mixture was neutralized with dilute hydrochloric acid and extracted with benzene to obtain a crystalline product with a yield of 93% (based on mercaptan). When this crystalline material was analyzed by infrared analysis (IR), nuclear magnetic resonance (NMR), and elemental analysis, the following analysis results were obtained.

IR: 1660 (C=0) Cm-1 NMR (CCl4, TMS): δ 725 (double line, IH, =CH-COO-) 585
Elemental analysis value (double line, 1H, -S-CH:): From this analysis result, it was confirmed that the above crystalline substance had the following structural formula.

n-Cl2H2, S-CH=CH-COOH reference example 3
Synthesis of methyl β-laurylsulfenyl acrylate β-laurylsulfenyl acrylic acid synthesized in Reference Example 2 (
0.3 mono(c), methanol (30 mol), concentrated sulfuric acid (
5.0d) was dissolved in benzene (400a) and heated to 80°C for 50 hours.

During that time, water was removed by benzene-water azeotropy. After the reaction was completed, the reaction mixture was concentrated under reduced pressure to obtain a crystalline product with a yield of 76%. When this crystalline product was analyzed, the following results were obtained. z Melting point 48-500C (from hexane) IR: 1710 (C=O)? -1 NMR (CCl4, TMS): δ 7.55 (double line, 1H, =CH-COO-), 5
80PF1 (double line, 1H, -S-CH=) elemental analysis value: From this analysis result, it was confirmed that the above crystalline substance had the following structural formula.

n-Cl, H2, S-CH=CH-COOCH3 Reference Example 4 Various β-sulfenyl acrylic acid esters were synthesized, and the reaction conditions and yields are shown in Table 1, and the physical properties of the products are shown in Table 2. Indicated.

Example 1 Sodium metaperiodate (NaIO4, 0.33 mol) is dissolved in a mixed solvent of H2O (200d)-MeOH (200ml).

The alcohol mixture obtained in Reference Example 1 (R=lauryl, (1)/()=1:0.86) (0.30 mono(c)) is added therein at room temperature.The reaction mixture is heated at 25°C. After stirring for 24 hours, the generated NaIO3 (sodium iodate) is filtered.The filtrate is extracted with ether to yield alcohol ([11) (3-laurylsulfinyl-2-propenol) and alcohol ([ V) (2-laurylsulfinyl-2-propenol) was isolated. The production ratio of alcohol (11 and alcohol (1V) was 1:0.86. Alcohol () and alcohol 0V) can be separated using a silica gel column. Alcohol (n[) (R = lauryl, n = 1): Liquid R: 3
300(0H), 1045(S=O)Cln-1.

NMR (CCl4, TMS): δ4.03 (4,2H1
allylic methylene), 5.36-5.85Pden(!N,
28 Olefin) Elemental analysis value From this analysis result, it was confirmed that the above liquid had the following structural formula.

Alcohol (IV) (R=Lauryl, n=1): Liquid I
R: 3300 (0H), 1040 (S=0) CfrL-
1.

NMR (CCl4, TMS): δ 4.96 (BrOa
d-mutual, 2H, allylic methylene), 5.39-5.83
PF (Nl,2Hl olefin). Elemental analysis value From this analysis result, it was confirmed that the above liquid had the following structural formula.Example 2 Alcohol mixture obtained in Reference Example 1 (R = lauryl, (1
)/()=1:0.86) (0.30 mol) or ethanol (500 ml).

30% hydrogen peroxide (0.40 mono(c)) was added to the solution and heated to 75°C for 8 hours.The reaction mixture was then poured into water and extracted with ether to produce alcohol (H) with a yield of 72%. and alcohol (1V) (R nilauryl, (NI)/(2 1:0.86). It was confirmed that they were the same.Example 3 The alcohol mixture obtained in Reference Example 1 (R nilauryl, (I
V()=1:0.86) (0.30 mol) is dissolved in chloroform (150T!Ll).

Meta-chloroperbenzoic acid (0.33
mol) in chloroform (150 mj) and stirred for 1 hour. The reaction mixture was poured into an aqueous sodium carbonate solution and extracted with ether to give alcohol () with a yield of 90%.
and alcohol (5) (R=lauryl, (self)
/(IV)=1:0.86) was obtained. It was confirmed that these alcohols (11, QV) were the same compounds as those obtained in Example 1. Example 4 Alcohol mixture obtained in Reference Example 1 (R = lauryl, (I
V()=1:0.86) (0.30 mol) in acetic acid (15
0WLI).

Peracetic acid (0.30 mol) was added to the solution at -10°C and stirred for 1 hour. The reaction mixture was poured into water and extracted with ether to yield a mixture of alcohol (11 and alcohol (5) (R=lauryl, (auto)/QV)= with a yield of 85%.
1:0.86) was obtained. These alcohols 1I), (
It was confirmed that IV) was the same compound as obtained in Example 1. Example 5CH2:C(SR)CH2OH
{R: CH3, C2OH4l, oleyl (Cl8H3,
), Ph(<Σ卜)} The production conditions and yields are shown in Table 3, and the physical properties are shown in Table 4.

Example 6 The alcohol mixture obtained in Reference Example 1 (R=lauryl, (1)/()=1:0.
86) (0.30 mol) and 30% hydrogen peroxide (0.80 mol)
mol) and heated at 80°C for 2 hours.

Then, the reaction mixture was poured into water and extracted with ether, resulting in 7
A mixture of alcohol (7) (3-laurylsulfonyl-2-propenol) and alcohol (V1 (2-laurylsulfonyl-2-propenol) was obtained with a yield of 8%. The production ratio is 1:0.8
It is 6. alcohol) and alcohol (V1) can be separated using a silica gel column. Alcohol (V) (R=
Lauryl, n=2): Melting point: 88-90°C (from hexane) IR: 3300 (0H), 1320, NMR (CCl4, TMS): δ4.01 (S, 2H.
allylic methylene), 5.30-5.781) PI (m
! , 2H, olefin).

Elemental analysis value violent crystal ~ ′▼ ノ 6V● violent crystal v●１
From the results of this analysis, it was confirmed that the crystalline substance had the following structural formula.

Alcono I (R=Lauryl, n22): Melting point: 95~
97°C (from hexane) IR: 3300 (0H), 1310, NMR (CCl,, TMS): δ490 (BrOad, 2H, allylic methylene), 5.25-5.801P
(!N, 2Hl olefin).

Elemental Analysis Values From the results of this analysis, it was confirmed that the above crystalline substance had the following structural formula.

Example 7 Alcohol mixture obtained in Reference Example 1 (R = lauryl, (1
)/()21:0.86) (0.30 mol) is dissolved in chloroform (1507!11).

Add meta-chloroperbenzoic acid (0.75
mol) in chloroform (150d) and stirred for 2 hours. The reaction mixture was poured into an aqueous sodium carbonate solution and extracted with ether, resulting in a yield of 92% (alcohol).
and alcohol (mixture (R=lauryl, (V)/(
VD=1:0.86) was obtained. It was confirmed that these alcohols (and (auto)) were the same as those obtained in Example 6. Example 8 Alcohol mixture obtained in Reference Example 1 (R = lauryl, (1
)/()=1:0.86) (0.30 mol) in acetic acid (1
50d).

Peracetic acid (0.65 mol) was added to the solution at -10°C and stirred for 1 hour. When the reaction mixture is poured into water and extracted with ether, the result is 80? A mixture of alcohol (and (V1) (R = lauryl, (/(VI) = 1:0.86) was obtained with a yield of It was confirmed that the compound was exactly the same as Example 9C20H41S oleyl (C!8H35)
Me\≦? ≧? ,yni:! The conditions and yields are shown in Table 5. Example 10 Sodium metaperiodide (NaIOOO.33 mol) was mixed with H,
β-laurylsulfenyl acrylic acid (0
．． 30 mol) at room temperature.

After stirring at 25°C for 24 hours, NaIO, (
The solution obtained by filtering the solution (sodium iodate) was extracted with ether to obtain a crystalline product with a yield of 88%.

When this crystalline substance was analyzed, the following results were obtained: Melting point: 62-65°C (from hexane) 1050 (S=O) NMR (CCl4, TMS): δ 7.25 (double line,
1H,=CH-COO-), 6.60 sir (double line, elemental analysis value; From this analysis result, it was confirmed that the above crystalline substance had the following structural formula. Sulfenyl acrylic acid (0.30 mol)
Dissolve in EtOH (300d).

Add 30% hydrogen peroxide (0.50 mol) to it and
Heat and stir at ℃ for 48 hours. The reaction mixture was extracted with ether to obtain a crystalline product with a yield of 68%. Analysis of this crystalline substance confirmed that it was the same crystalline substance obtained in Example 10. Example 12 β-laurylsulfenyl acrylic acid (0.30 mono(
Dissolve c) in chloroform (200d).

A solution of meta-chloroperbenzoic acid (0.33 mol) in chloroform (100d) was added thereto at 25°C. After stirring for 1 hour, the mixture was extracted with ether to obtain a crystalline product with a yield of 90%.

Analysis of this crystalline substance confirmed that it was the same crystalline substance obtained in Example 10. Example 13 β-laurylsulfenyl acrylic acid (0.30 mol)
Dissolve in AcOH (200d).

Peracetic acid (0.30 mol) was added to it at -10°C,
Stir for 1 hour. The reaction mixture was divided with water and extracted with ether to obtain a crystalline product with a yield of 70%. Analysis of this crystalline substance confirmed that it was the same crystalline substance obtained in Example 10. Example 14 Various β-sulfinyl acrylic acids, their esters and amides were synthesized, and the reaction conditions and yields are shown in Table 7, and the physical properties of the products are shown in Table 8.

Example 15 β-laurylsulfenyl acrylic acid (0.30 mol) was dissolved in acetic acid (200 d), 30% hydrogen peroxide (0.70 mol) was added thereto, and the mixture was heated to 80°C for 1 hour. did.

The reaction mixture was poured into water, extracted with ether, and the ether layer was washed with water. The ether was then removed to obtain a crystalline product. The analytical values of this crystal are as follows. Elemental analysis value: From this analysis result, it was confirmed that the above crystalline substance had the following structural formula.

Example 16 Various β-sulfonylacrylic acids, their esters and amides were synthesized, and the reaction conditions and yields are shown in Table 9, and the physical properties of the products are shown in Table 10.

Example 17 The drug concentration in the medium required to inhibit the growth of various bacteria was determined according to the mixed agar medium test method of active group and growth inhibiting effect drug against Gram-positive bacteria and Gram-negative bacteria.

That is, 1 d of a drug solution at a predetermined concentration was taken, placed in a Petri dish, and then 19 ml of dissolved ordinary agar medium was added thereto, stirred uniformly, and allowed to cool and solidify.

On the surface, apply a loopful of bacterial solution prepared so that the number of microorganisms is 1 million per 11n1, and store it in a greenhouse at 30°C for 72 hours.
After culturing for a period of time, the minimum inhibitory concentration of the drug in the medium was determined from the growth status of the bacteria. The results are shown in Tables 11-18. +: Growth occurs, and no growth inhibition effect is observed.

±: Slight growth, growth inhibiting effect is observed. -: Growth is completely inhibited, and growth inhibiting effect is recognized. Example
18 Test of mold and yeast growth inhibition efficacy Dry heat sterilized 9C7! 19ml of Sabouraud agar medium prepared by heating and dissolving 1ml of a drug solution at a predetermined concentration in a L-sized Petri dish.
1 and mixed uniformly, solidified and made into a flat plate.

On this drug-mixed Sabouraud agar medium,
- According to the mold resistance test method of Z-2911, each of spore suspensions of Penicillium cyutrinum, Aspergillus nigai and Trichobiton mentaglophiites and a suspension of Candida albicans, a representative yeast, were I took a loopful of it and applied it.

After culturing in a thermostatic chamber at 25° C. for 5 days, the growth of mold and yeast was observed, the minimum growth-inhibiting concentration was determined, and the efficacy was tested.

Claims (1)

[Claims] 1. A compound RSO_n- represented by the following general formula (1)
CH=CHX (1) [In the formula, R represents an alkyl group, an alkenyl group, or an aryl group having 1 to 20 carbon atoms. X is CH_2OH or COY. Tazoshi Y is a hydroxyl group or its alkali metal, alkaline earth metal or NH_
4, an alkoxy group having an alkyl group having 1 to 20 carbon atoms, an alkoxyethoxy group or an alkoxypolyethenoxy group, a polyvalent compound which may have an ether bond formed by intramolecular or intermolecular dehydration. an alkoxy group formed by removing H from one OH group of an alcohol, or NR'R'' (where R' is a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, or a hydroxy group having 2 to 6 carbon atoms); is an alkyl group, R″ is a hydrogen atom,
an alkyl group having 1 to 20 carbon atoms or an alkyl group having 2 to 6 carbon atoms substituted with a hydroxyl group or a sulfonic acid group in the form of a salt). n is 1 or 2. [2] The compound according to claim 1, wherein R in the general formula (1) is a straight-chain alkyl group or alkenyl group having 3 to 18 carbon atoms. 3. The compound according to claim 1, wherein n is 1 in general formula (1). 4. The compound according to claim 2 or 3, wherein in general formula (1), X is CH_2OH. 5. The compound according to claim 2 or 3, wherein in general formula (1), X is COY (Y is the same as above). 6. The compound according to claim 5, wherein Y in general formula (1) is a hydroxyl group or an alkali metal salt thereof. 7 In general formula (1), Y has an alkyl group with 1 to 3 carbon atoms, an alkoxy group, an alkoxyethoxy group, or an alkoxydiethenoxy group, ▲There are mathematical formulas, chemical formulas, tables, etc.▼, ▲Mathematical formulas, chemical formulas, tables, etc. There are ▼, -O(CH_2CH_2O)mH (m=1~12), ▲
The compound according to claim 5, which is selected from the group consisting of mathematical formulas, chemical formulas, tables, etc. 8 In general formula (1), Y is NR'R''(R' and R
9. The compound according to claim 5, in which " is the same as defined above. 9 In the general formula (1), Y is NR'R", and R'
is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a hydroxyalkyl group having 2 to 3 carbon atoms, and R'' is a hydrogen atom, an alkyl group having 1 to 3 carbon atoms, or a hydroxyalkyl group having 2 to 3 carbon atoms; 9. The compound according to claim 8, which is an alkyl group having 2 to 3 carbon atoms substituted with 1 to 3 hydroxyalkyl groups or a sulfonic acid group in the form of a salt.