KR102162475B1 - Branched dicarboxylic compound having anhydrosugar alcohol core and alkylene oxide extender and method for preparing the same - Google Patents

Abstract

The present invention relates to a branched dicarboxyl compound having an anhydrosugar alcohol nucleus and an alkylene oxide extension, and a method for preparing the same, and more particularly, to the addition of alkylene oxide using a renewable plant-based anhydrosugar alcohol as a raw material , A branched dicarboxyl having an anhydrosugar alcohol nucleus and an alkylene oxide extension, which is prepared through reaction with a nitrile compound and addition of sodium hydroxide or alcohol, and can be used as a monomer of polymer condensation polymerization, or as an antibacterial and/or antifungal agent. It relates to a compound and a method for preparing the same.

Description

A branched dicarboxyl compound having an anhydrosugar alcohol nucleus and an alkylene oxide extension, and a manufacturing method thereof TECHNICAL FIELD [BRANCHED DICARBOXYLIC COMPOUND HAVING ANHYDROSUGAR ALCOHOL CORE AND ALKYLENE OXIDE EXTENDER AND METHOD FOR PREPARING THE SAME}

The present invention relates to a branched dicarboxyl compound having an anhydrosugar alcohol nucleus and an alkylene oxide extension, and a method for preparing the same, and more particularly, to the addition of alkylene oxide using a renewable plant-based anhydrosugar alcohol as a raw material , A branched dicarboxyl having an anhydrosugar alcohol nucleus and an alkylene oxide extension, which is prepared through reaction with a nitrile compound and addition of sodium hydroxide or alcohol, and can be used as a monomer of polymer condensation polymerization, or as an antibacterial and/or antifungal agent. It relates to a compound and a method for preparing the same.

Hydrogenated sugar (also referred to as “sugar alcohol”) refers to a compound obtained by adding hydrogen to the reducing end group of a sugar, and generally HOCH ₂ (CHOH) _n CH ₂ OH (where n is an integer of 2 to 5 ), and classified into tetritol, pentitol, hexitol and heptitol (4, 5, 6 and 7 carbon atoms, respectively) according to the number of carbon atoms. Among them, hexitol having 6 carbon atoms includes sorbitol, mannitol, iditol, galactitol, and the like, and sorbitol and mannitol are particularly effective substances.

Anhydrosugar alcohol has the form of a diol having two hydroxy groups in the molecule, and can be prepared using hexitol derived from starch (e.g., Korean Patent No. 10-1079518, Korean Patent Laid-Open No. 10 -2012-0066904). Since anhydrosugar alcohol is an eco-friendly material derived from renewable natural resources, research on its manufacturing method has been conducted with much interest from a long time ago. Among these anhydrosugar alcohols, isosorbide prepared from sorbitol has the widest industrial application range.

The use of anhydrosugar alcohol is very diverse, such as treatment of heart and vascular diseases, adhesives for patches, pharmaceuticals such as mouthwash, solvents for compositions in the cosmetic industry, and emulsifiers in the food industry. In addition, it can raise the glass transition temperature of polymer materials such as polyester, PET, polycarbonate, polyurethane, epoxy resin, etc., and has the effect of improving the strength of these materials, and because it is an eco-friendly material derived from natural products, useful. In addition, it is known that it can be used as an eco-friendly solvent for adhesives, eco-friendly plasticizers, biodegradable polymers, and water-soluble lacquers.

In this regard, International Patent Publication No. 2013-173020 discloses a dicarboxylic acid material having an isosorbide nucleus and a method of manufacturing the same, but the manufacturing cost is high and the manufacturing process is performed using an expensive raw material (triflic anhydride). There is a problem that commercial production is difficult using an acid component as a catalyst in the step of converting this complex, nitrile functional group to carboxylic acid.

Accordingly, there is a need for a branched dicarboxyl compound having an anhydrosugar alcohol nucleus and a method for preparing the same, which is cheaper in manufacturing cost compared to the previous manufacturing method, the manufacturing process can be simplified, and commercial production is easy.

An object of the present invention is prepared by addition of alkylene oxide, reaction with a nitrile compound, and addition of sodium hydroxide or alcohol using a renewable plant-based anhydrosugar alcohol as a raw material, a monomer of polymer condensation polymerization, or an antimicrobial agent and/ Or it is to provide a branched dicarboxyl compound having an anhydrosugar alcohol nucleus and an alkylene oxide extension, which can be used as an antifungal agent, and a method for preparing the same.

In order to solve the above technical problem, the present invention provides a compound represented by the following formula A:

[Formula A]

X-Y-O-M-O-Y'-X

In Formula A,

X is -COOR ₄ , wherein each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,

Y is -[CH ₂ CHR ₁ O] _m -CHR ₂ CHR ₃ -,

Y'is -[CH ₂ CHR ₁ O] _n -CHR ₂ CHR ₃ -,

Wherein each R ₁ is independently hydrogen, alkyl or aryl,

R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,

m and n are each independently an integer of 0 to 15,

m+n is an integer from 1 to 25,

M is a divalent organic group derived from anhydrosugar alcohol.

According to another aspect of the present invention, (1) performing a Michael reaction of an anhydrosugar alcohol-alkylene oxide adduct and a nitrile compound; And (2) adding sodium hydroxide or alcohol to the compound obtained from the Michael reaction, there is provided a method for preparing a compound represented by Formula A:

[Formula A]

X-Y-O-M-O-Y'-X

In Formula A,

X is -COOR ₄ , wherein each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,

Y is -[CH ₂ CHR ₁ O] _m -CHR ₂ CHR ₃ -,

Y'is -[CH ₂ CHR ₁ O] _n -CHR ₂ CHR ₃ -,

Wherein each R ₁ is independently hydrogen, alkyl or aryl,

R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,

m and n are each independently an integer of 0 to 15,

m+n is an integer from 1 to 25,

M is a divalent organic group derived from anhydrosugar alcohol.

According to another aspect of the present invention, there is provided an antimicrobial composition comprising the compound represented by Formula A according to the present invention.

According to another aspect of the present invention, there is provided an antifungal composition comprising the compound represented by formula A according to the present invention.

According to another aspect of the invention, there is provided a formulation comprising the antimicrobial composition according to the invention.

According to another aspect of the present invention, there is provided a formulation comprising an antifungal composition according to the present invention.

The branched dicarboxyl compound having an anhydrosugar alcohol nucleus and an alkylene oxide extension of the present invention is a renewable plant-based anhydrosugar alcohol as a raw material, the addition of alkylene oxide, reaction with a nitrile compound, and sodium hydroxide or alcohol addition Since it is manufactured through environmentally friendly, manufacturing cost can be reduced, the manufacturing process can be simplified, and commercial production is easy by using a base component as a catalyst in the step of converting a nitrile functional group to a carboxylic acid.

In addition, the antimicrobial and antifungal compositions of the present invention contain a branched dicarboxyl compound having an anhydrosugar alcohol nucleus and an alkylene oxide extension that exhibits excellent effects on the growth inhibition of microorganisms including bacteria and fungi, As an eco-friendly preservative, it can be used in a variety of products such as cosmetics, skin care agents, detergents, colorants, paints, and plant protectants.

Hereinafter, the present invention will be described in detail.

The present invention provides a compound represented by the following formula A:

[Formula A]

X-Y-O-M-O-Y'-X

In Formula A,

X is -COOR ₄ , wherein each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,

Y is -[CH ₂ CHR ₁ O] _m -CHR ₂ CHR ₃ -,

Y'is -[CH ₂ CHR ₁ O] _n -CHR ₂ CHR ₃ -,

Wherein each R ₁ is independently hydrogen, alkyl or aryl,

R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,

m and n are each independently an integer of 0 to 15,

m+n is an integer from 1 to 25,

M is a divalent organic group derived from anhydrosugar alcohol.

The anhydrosugar alcohol is prepared from hydrogenated sugars derived from natural products.

Hydrogenated sugar (also referred to as “sugar alcohol”) refers to a compound obtained by adding hydrogen to the reducing end group of a sugar, and generally HOCH ₂ (CHOH) _n CH ₂ OH (where n is an integer of 2 to 5 ), and classified into tetritol, pentitol, hexitol and heptitol (4, 5, 6 and 7 carbon atoms, respectively) according to the number of carbon atoms.

Among them, hexitol having 6 carbon atoms includes sorbitol, mannitol, iditol, galactitol, and the like, and sorbitol and mannitol are particularly effective substances.

Anhydrosugar alcohol has the form of a diol having two hydroxy groups in the molecule, and can be prepared using hexitol derived from starch (e.g., Korean Patent No. 10-1079518, Korean Patent Laid-Open No. 10 -2012-0066904). Since anhydrosugar alcohol is an eco-friendly material derived from renewable natural resources, research on its manufacturing method has been conducted with much interest from a long time ago. Among these anhydrosugar alcohols, isosorbide prepared from sorbitol has the widest industrial application range.

In the compound represented by Formula A of the present invention, M is an anhydrosugar alcohol, isosorbide (1,4-3,6-dianhydrosorbitol), isomannide (1,4-3,6-dianhydromannitol) Alternatively, it may be a divalent organic group derived from isoidide (1,4-3,6-dianhydroiditol), and in one embodiment, M may be selected from the following formula.

In the compound represented by Formula A of the present invention, X is -COOR ₄ , wherein R ₄ is each independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl. In addition, Y is -[CH ₂ CHR ₁ O] _m -CHR ₂ CHR ₃ -, and Y'is -[CH ₂ CHR ₁ O] _n -CHR ₂ CHR ₃ -, where R ₁ is each independently hydrogen, Alkyl or aryl, and R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl.

The alkyl is, for example, a substituted or unsubstituted linear alkyl having 1 to 10 carbon atoms (more specifically 1 to 6), or a branched substituted or unsubstituted carbon number 3 to 10 (more specifically 3 to 6) It may be alkyl, and the aryl may be, for example, a substituted or unsubstituted monocyclic aryl, polycyclic aryl, or fused cyclic aryl having 6 to 14 carbon atoms (more specifically, 6 to 12). In addition, the arylalkyl may be a substituted or unsubstituted arylalkyl having 7 to 24 carbon atoms (more specifically 7 to 18), and the cycloalkyl may be, for example, a substituted or unsubstituted 3 to 8 carbon atoms (more specifically It may be a cycloalkyl of 3 to 6). In addition, the heteroaryl is a substituted or unsubstituted 5 to 12 membered (more specifically 5 to 10 membered) monocyclic hetero atom including one or more hetero atoms selected from N, O, S It may be an aryl, polycyclic heteroaryl, or fused cyclic heteroaryl.

The groups are, for example, one or more substituents selected from C1-C10 alkyl (e.g., methyl, ethyl, propyl, butyl, etc.) or C6-C10 aryl (e.g., phenyl, benzyl, tolyl, etc.) Can be substituted.

In one embodiment, the compound represented by Formula A of the present invention may be a compound represented by the following Formula 1:

[Formula 1]

In Formula 1,

Each R ₁ is independently hydrogen, alkyl or aryl,

R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,

Each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,

m and n are each independently an integer of 0 to 15,

m+n is an integer from 1 to 25.

In one embodiment, the compound represented by Formula A of the present invention may be a compound represented by the following Formulas 1-1 to 1-6.

[Formula 1-1]

[Formula 1-2]

[Formula 1-3]

[Formula 1-4]

[Formula 1-5]

[Formula 1-6]

In Formulas 1-1 to 1-6, m and n are as defined in Formula 1.

In one embodiment, the compound represented by Formula A of the present invention may be a compound represented by the following Formula 2:

[Formula 2]

In Chemical Formula 2,

Each R ₁ is independently hydrogen, alkyl or aryl,

R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,

Each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,

m and n are each independently an integer of 0 to 15,

m+n is an integer from 1 to 25.

In one embodiment, the compound represented by Formula A of the present invention may be a compound represented by the following Formulas 2-1 to 2-6.

[Formula 2-1]

[Formula 2-2]

[Formula 2-3]

[Formula 2-4]

[Formula 2-5]

[Formula 2-6]

In Formulas 2-1 to 2-6, m and n are as defined in Formula 2.

In one embodiment, the compound represented by Formula A of the present invention may be a compound represented by the following Formula 3:

[Formula 3]

In Chemical Formula 3,

Each R ₁ is independently hydrogen, alkyl or aryl,

R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,

Each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,

m and n are each independently an integer of 0 to 15,

m+n is an integer from 1 to 25.

In one embodiment, the compound represented by Formula A of the present invention may be a compound represented by the following Formulas 3-1 to 3-6.

[Formula 3-1]

[Chemical Formula 3-2]

[Chemical Formula 3-3]

[Formula 3-4]

[Formula 3-5]

[Formula 3-6]

In Chemical Formulas 3-1 to 3-6, m and n are as defined in Chemical Formula 3.

According to another aspect of the present invention, (1) performing a Michael reaction of an anhydrosugar alcohol-alkylene oxide adduct and a nitrile compound; And (2) adding sodium hydroxide or alcohol to the compound obtained from the Michael reaction, there is provided a method for preparing a compound represented by Formula A:

[Formula A]

X-Y-O-M-O-Y'-X

In Formula A,

X is -COOR ₄ , wherein each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,

Y is -[CH ₂ CHR ₁ O] _m -CHR ₂ CHR ₃ -,

Y'is -[CH ₂ CHR ₁ O] _n -CHR ₂ CHR ₃ -,

Wherein each R ₁ is independently hydrogen, alkyl or aryl,

R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,

m and n are each independently an integer of 0 to 15,

m+n is an integer from 1 to 25,

M is a divalent organic group derived from anhydrosugar alcohol.

In one embodiment, the method of preparing the compound represented by Formula A may further include adding an alkylene oxide to both ends of the anhydrosugar alcohol before performing the Michael reaction. In this case, 1 to 30 molar equivalents of alkylene oxide may be added to 1 molar equivalent of anhydrosugar alcohol. If the molar equivalent of the alkylene oxide is too low, the yield of the anhydrosugar alcohol-alkylene oxide adduct is lowered, and if the molar equivalent is too high, it is difficult to expect additional effects, and the manufacturing cost increases.

In one embodiment, the alkylene oxide may be a C2 to C8 linear or C3 to C8 branched alkylene oxide, and more specifically, may be selected from ethylene oxide, propylene oxide, or a combination thereof. .

In one embodiment, the alkylene oxide addition reaction may be carried out at a temperature of 100 to 200 °C, preferably 120 to 160 °C, for 1 to 10 hours, preferably 2 to 4 hours.

In the above step (1), the anhydrosugar alcohol is isosorbide (1,4-3,6-dianhydrosorbitol), isomannide (1,4-3,6-dianhydromannitol) or isoidide (1, 4-3,6-dianhydroiditol).

The nitrile compounds used in step (1) of the production method of the present invention include acrylonitrile, methacrylonitrile, crotononitrile, cinnamonitrile, 3-(furan-2-yl)prop-2-ennitrile. , Cyclohexane acrylonitrile, or a combination thereof may be used, but is not limited thereto.

In performing the Michael reaction of the anhydrosugar alcohol-alkylene oxide adduct and the nitrile compound, the reaction may be carried out in a ratio of 1 to 10 molar equivalents of the nitrile compound to 1 molar equivalent of the anhydride alcohol-alkylene oxide adduct. When the molar equivalent of the nitrile compound is too low, the yield of the compound represented by Formula A decreases, and when the molar number is too high, it is difficult to expect additional effects, and the manufacturing cost increases.

The Michael reaction may be performed in the presence of a base catalyst, and is not particularly limited, but the Michael reaction may be performed in the presence of 0.005 to 0.05 molar equivalents of a base catalyst per 1 molar equivalent of an anhydrosugar alcohol-alkylene oxide adduct. If the content of the base catalyst is too low, the reaction rate of the Michael reaction becomes slow, and if the content is too high, it is difficult to expect additional effects, and the manufacturing cost increases.

Although the type of the base catalyst is not particularly limited, for example, a hydroxide of an alkali metal (specifically, a hydroxide of Li, Na, K, Rb or Cs), a hydroxide of an alkaline earth metal (specifically, Mg, Ca, Sr Or a hydroxide of Ba), carbonates of alkali metals (specifically, carbonates of Li, Na, K, Rb or Cs), alcoholates of alkali metals or alkaline earth metals (specifically, sodium methylate, sodium ethylate or potassium t-butylate, etc.), or a basic organic catalyst (specifically, 1,8-diazabicyclo[5.4.0]undec-7-ene (1,8-Diazabicyclo[5.4.0]undec-7-ene) ), 4- (dimethylamino) pyridine (4- (Dimethylamino) pyridine), etc.) can be used, preferably a basic organic catalyst can be used. When a basic organic catalyst is used as the base catalyst, the Michael reaction (nitrile addition reaction) speed is accelerated compared to the basic inorganic catalyst, thereby solving a serious heat generation problem due to accumulation of unreacted raw materials when the nitrile compound is added.

In step (1) of performing the Michael reaction of the anhydrosugar alcohol-alkylene oxide adduct and the nitrile compound, a step of stirring the product of the Michael reaction for 1 to 10 hours may be included. If the stirring time is too short, the yield of the compound represented by Formula A may be lowered. Conversely, if the stirring time is too long, it is difficult to expect additional effects.

The product of the Michael reaction may be cooled to room temperature after the stirring step, and the cooled product of the Michael reaction is used in an organic solvent (eg, ethyl acetate, dichloromethane, 2-methyltetrahydrofuran, diethyl ether, etc.). After dilution, it can be washed sequentially with aqueous hydrochloric acid, aqueous sodium hydroxide, and distilled water. After that, the step of concentrating under reduced pressure may be further performed.

In the method for producing the compound represented by Formula A, the anhydride alcohol, the nitrile compound, and R ₁ and R ₂ are the same as described above.

In one embodiment, the compound obtained from the step of adding an alkylene oxide to both ends of an anhydrosugar alcohol may be an anhydrosugar alcohol-alkylene oxide adduct, such as isosorbide (ISB)-alkylene oxide of the following formula (4) It may be an adjunct.

[Formula 4]

In Chemical Formula 4,

Each R ₁ is independently hydrogen, alkyl or aryl,

m and n are each independently an integer of 0 to 15,

m+n is an integer from 1 to 25.

In the step (2) of adding sodium hydroxide or alcohol to the compound obtained from the Michael reaction in the production method of the present invention, the alcohol is not particularly limited, but a substituted or unsubstituted (specifically, an alkyl group having 1 to 10 carbon atoms (e.g. For example, methyl, ethyl, propyl, butyl, etc.), a cycloalkyl group having 3 to 10 carbon atoms (for example, cyclohexyl, etc.) or an aryl group having 6 to 10 carbon atoms (for example, phenyl, benzyl, tolyl, etc.) Substituted or unsubstituted) aliphatic or aromatic alcohols may be used, and those selected from methanol, 2-propanol, benzyl alcohol, phenol, cyclohexanol, or mixtures thereof may be used.

In the step (2), 50 to 150 g of sodium hydroxide or 0.05 to 2 L of alcohol may be added to 100 g of the compound obtained from the Michael reaction.

In one embodiment, the compound represented by Formula A obtained through the step (2) may be an anhydrosugar alcohol-dicarboxylic acid compound or an anhydrosugar alcohol-diester compound, and in one embodiment ISB- It may be a dicarboxylic acid compound or an ISB-diester compound.

In one embodiment, in the step (2), when sodium hydroxide is added, after the reflux stirring step, the step of cooling to room temperature is performed, and then conc. After lowering the pH by adding HCl (for example, lowering the pH to 1 to 3), the step of concentrating may be performed. After the concentration step, acetone, tetrahydrofuran, acetonitrile, etc. are added as a salt extraction solvent, followed by stirring to remove the salt and filtering, and then the filtrate is concentrated to obtain an anhydrosugar alcohol-dicarboxylic acid compound (e.g. For example, an ISB-dicarboxylic acid compound) can be obtained.

In one embodiment, in the step (2), when alcohol is added, an acid component (eg, sulfuric acid, phosphoric acid, hydrochloric acid, etc.) is added dropwise, followed by reflux stirring, and then cooling to room temperature is performed. Then, a basic component (eg, a hydroxide of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, lithium hydroxide, etc.) is added to adjust the PH to 7-9, and then distillation under reduced pressure can be performed. Subsequently, the concentrate is diluted with an organic solvent (e.g., ethyl acetate, dichloromethane, 2-methyltetrahydrofuran, diethyl ether, etc.), washed once or more with purified water, and then concentrated under reduced pressure to obtain anhydrosugar alcohol- A diester compound (for example, an ISB-diester compound) can be obtained. The content of the basic component is not particularly limited, but may be preferably 1N to 5N. If the content of the basic component is too low, the reaction rate is slowed, and if the content is too high, it is difficult to expect additional effects, and manufacturing cost increases.

In the step (2), the reaction mixture obtained by adding sodium hydroxide or alcohol to the compound obtained from the Michael reaction may be refluxed and stirred for 1 to 30 hours. If the stirring time is too short, the yield of the compound represented by Formula A may be lowered. Conversely, if the stirring time is too long, it is difficult to expect additional effects.

The compound represented by Formula A of the present invention can be used as a monomer for polymer condensation polymerization.

According to another aspect of the present invention, there is provided an antimicrobial composition or an antifungal composition comprising the compound represented by Formula A.

The compound represented by Formula A contained in the antimicrobial and antifungal compositions of the present invention is prepared from renewable plant-based low-cost raw materials, and exhibits excellent effects on the growth inhibition of microorganisms including bacteria and fungi, etc. It can be used as a preservative in products of Since the composition of the present invention exhibits antifungal properties as well as antibacterial properties, it can be used in various formulations.

The content of the compound represented by Formula A included in the antimicrobial composition of the present invention may be 0.005 to 30% by weight, based on 100% by weight of the antimicrobial composition. For example, the lower limit of the content of the compound represented by Formula A is 0.005% by weight or more, 0.007% by weight or more, 0.01% by weight or more, 0.012% by weight or more, 0.015% by weight or more, 0.02% by weight or more, based on 100% by weight of the antimicrobial composition. , 0.05% or more, 0.1% or more, 0.5% or more, 0.7% or more, 1% or more, 1.2% or more, 1.5% or more, 2% or more, 3% or more, 5% or more , 7 wt% or more, 10 wt% or more, 15 wt% or more, or 20 wt% or more. In addition, the upper limit of the content of the compound represented by Formula A is 30 wt% or less, 20 wt% or less, 15 wt% or less, 10 wt% or less, 9 wt% or less, 8.5 wt% or less, based on 100 wt% of the antimicrobial composition , 8 wt% or less, 7 wt% or less, 5 wt% or less, 3 wt% or less, or 2 wt% or less. When the content of the compound represented by Formula A is lower than the above numerical range, the effect of inhibiting the growth of microorganisms (specifically, bacteria) may be insignificant, whereas when the content is higher than the above numerical range, an additional effect cannot be obtained.

The antimicrobial composition of the present invention includes phenoxyethanol, alkanediol, methylchloroisothiazolinone, methylisothiazolinone, benzoic acid or a salt thereof, a benzoic acid ester derivative, salicylic acid or a salt thereof, 4-hydroxy benzoic acid or a salt thereof, Sorbic acid or a salt thereof, dehydroacetic acid or a salt thereof, dehydroacetic acid ester derivative, benzyl alcohol, 2-methylisothiazole-3(2H)-one, 4-isopropyl-m-cresol or zinc pyrithione It may further comprise one or more additives selected from the group. Although not particularly limited, the content of the additive is 0.1 to 50% by weight, for example, 0.5% by weight or more, 1% by weight or more, 5% by weight or more, 10% by weight or more, 20% by weight or more, based on 100% by weight of the antimicrobial composition. Alternatively, it may be 30 wt% or more, and may be 45 wt% or less, 40 wt% or less, 35 wt% or less, 30 wt% or less, 20 wt% or less, or 15 wt% or less.

The content of the compound represented by Formula A included in the antifungal composition of the present invention may be 0.005 to 30% by weight based on 100% by weight of the antifungal composition. For example, the lower limit of the content of the compound represented by Formula A is 0.005% by weight or more, 0.007% by weight or more, 0.01% by weight or more, 0.012% by weight or more, 0.05% by weight or more, 0.1% by weight, based on 100% by weight of the antifungal composition. Or more, 0.5% or more, 0.7% or more, 1% or more, 1.2% or more, 1.5% or more, 2% or more, 3% or more, 5% or more, 7% or more, 10% by weight It may be more than, 15% by weight or more, or 20% by weight or more. In addition, the upper limit of the content of the compound represented by Formula A is 30 wt% or less, 20 wt% or less, 15 wt% or less, 10 wt% or less, 9 wt% or less, 8.5 wt% based on 100 wt% of the antifungal composition. It may be less than, 8% by weight or less, 7% by weight or less, 5% by weight or less, 3% by weight or less, or 2% by weight or less. When the content of the compound represented by Formula A is lower than the above numerical range, the effect of inhibiting the growth of microorganisms (specifically, fungi) may be insignificant, whereas when the content is higher than the above numerical range, additional effects cannot be obtained.

The antifungal composition of the present invention includes phenoxyethanol, alkanediol, methylchloroisothiazolinone, methylisothiazolinone, benzoic acid or salt thereof, benzoic acid ester derivative, salicylic acid or salt thereof, 4-hydroxy benzoic acid or salt thereof , Sorbic acid or salt thereof, dehydroacetic acid or salt thereof, dehydroacetic acid ester derivative, benzyl alcohol, 2-methylisothiazole-3(2H)-one, 4-isopropyl-m-cresol or zinc pyrithione It may further include one or more additives selected from the group consisting of. Although not particularly limited, the content of the additive is 0.1 to 50% by weight, such as 0.5% by weight or more, 1% by weight or more, 5% by weight or more, 10% by weight or more, 20% by weight, based on 100% by weight of the antifungal composition. It may be greater than or equal to 30% by weight, and may be 45% by weight or less, 40% by weight or less, 35% by weight or less, 30% by weight or less, 20% by weight or less, or 15% by weight or less.

According to another aspect of the present invention, there is provided a formulation comprising the aforementioned antimicrobial composition, antifungal composition or a combination thereof.

The antimicrobial and antifungal compositions of the present invention have an excellent effect on inhibiting the growth of microorganisms by measuring the minimum inhibitory concentration (MIC) for a number of bacteria and fungi, as described in Examples to be described later. As confirmed, it can be included as a preservative in various products. The antimicrobial composition, antifungal composition or a combination thereof of the present invention may be, for example, a preparation selected from the group consisting of cosmetics, skin care agents, detergents, colorants, paints, or plant protectants, but limited thereto. It doesn't work.

Hereinafter, the present invention will be described in more detail through Examples and Comparative Examples. However, the scope of the present invention is not limited to these.

[ Example ]

<Isosorbide-alkylene Oxide Preparation of additives>

Manufacturing example 1-1 to 1-4: isosorbide-ethylene Oxide Preparation of adducts (in formula 4, m+n=3, 5, 10 or 25, R _One =hydrogen)

1 mole of isosorbide (146 g); 3, 5, 10 or 25 moles of ethylene oxide (132 g, 220 g, 441 g or 1,101 g); And sodium hydroxide (0.4 g) as a catalyst was placed in a reaction apparatus capable of pressurizing a column equipped with a nitrogen gas pipe and a cooling device, a stirrer, a thermometer, and a heater, and gradually heated up. Isosorbide in a form in which hydrogen of the hydroxy groups at both ends of isosorbide is substituted with 3 mol, 5 mol, 10 mol or 25 mol ethylene oxide groups by reacting while maintaining at a temperature of 120°C to 160°C for 2 to 4 hours -Ethylene oxide 3 mole adduct (Preparation Example 1-1), isosorbide-ethylene oxide 5 mole adduct (Preparation Example 1-2), isosorbide-ethylene oxide 10 mole adduct (Preparation Example 1-3) And isosorbide-ethylene oxide 25 mole adducts (Preparation Example 1-4), respectively.

Manufacturing example 2-1 to 2-4: isosorbide-propylene Oxide Preparation of adducts (in formula 4, m+n=3, 5, 10 or 25, R _One = methyl )

1 mole of isosorbide (146 g); 3, 5, 10 or 25 moles of propylene oxide (174 g, 290 g, 581 g or 1,452 g); And sodium hydroxide (0.4 g) as a catalyst was placed in a reaction apparatus capable of pressurizing a column equipped with a nitrogen gas pipe and a cooling device, a stirrer, a thermometer, and a heater, and gradually heated up. Isosorbide in a form in which hydrogen of the hydroxy groups at both ends of isosorbide is substituted with 3 mol, 5 mol, 10 mol, or 25 mol propylene oxide groups by reacting while maintaining at a temperature of 120°C to 160°C for 2 hours to 4 hours -Propylene oxide 3 mole adduct (Preparation Example 2-1), isosorbide-propylene oxide 5 mole adduct (Preparation Example 2-2), isosorbide-propylene oxide 10 mole adduct (Preparation Example 2-3) And isosorbide-propylene oxide 25 mole adducts (Preparation Example 2-4), respectively.

<Isosorbide- Dinitrile Preparation of compound (step (1))>

Example A1-1 to A1-4: isosorbide-ethylene Oxide Adjunct Of diacrylonitrile Produce

The isosorbide-ethylene oxide 3 mol adduct (1 mol) prepared in Preparation Examples 1-1 to 1-4, isosorbide-ethylene oxide 5 mol adduct (1 mol), isosorbide-ethylene oxide 10 Each of the molar adduct (1 mole) and the isosorbide-ethylene oxide 25 mole adduct (1 mole) was added to a glass reactor together with 1.5 g (0.01 mole) of 1,8-Diazabicyclo[5.4.0]undec-7-ene. Then, after the internal temperature was raised to 70 ~ 75 ℃, acrylonitrile 159g (3 mol) was slowly added dropwise for about 4 hours so that the internal temperature did not exceed 80 ℃. After the dropwise addition was completed, the mixture was stirred for 3 hours while adjusting the internal temperature to 70-75°C, and then cooled to room temperature. The reaction mixture was diluted with 500 g of ethyl acetate, and then washed sequentially with 250 g of 1 normal hydrochloric acid aqueous solution, 250 g of 1 normal sodium hydroxide aqueous solution, and 250 g of distilled water, and then concentrated under reduced pressure to diacrylic as an adduct of 3 mol of isosorbide-ethylene oxide. Nitrile (Example A1-1, in the following formula 5-1, in the case of m+n=3), diacrylonitrile of isosorbide-ethylene oxide 5 mol adduct (Example A1-2, following formula 5-1 In, m + n = 5), isosorbide-diacrylonitrile of 10 mol adducts of ethylene oxide (Example A1-3, in the following formula 5-1, m + n = 10) and isosorb Diacrylonitrile (in Example A1-4, in the following formula 5-1, m+n=25) of a 25 mole adduct of bead-ethylene oxide was obtained in a yield of 85% to 95%.

[Chemical Formula 5-1]

Example A2-1 to A2-4: isosorbide-propylene Oxide Adjunct Of diacrylonitrile Produce

The isosorbide-propylene oxide 3 mole adduct (1 mole) prepared in Preparation Examples 2-1 to 2-4, isosorbide-propylene oxide 5 mole adduct (1 mole), isosorbide-propylene oxide 10 Each of the molar adduct (1 mole) and the isosorbide-propylene oxide 25 mole adduct (1 mole) was added to a glass reactor with 1.5 g (0.01 mole) of 1,8-Diazabicyclo[5.4.0]undec-7-ene. Then, after the internal temperature was raised to 70 ~ 75 ℃, 159g (3 mol) of acrylonitrile was slowly added dropwise for about 4 hours so that the internal temperature did not exceed 80 ℃. After the dropwise addition was completed, the mixture was stirred for 3 hours while adjusting the internal temperature to 70-75°C, and then cooled to room temperature. The reaction mixture was diluted with 500 g of ethyl acetate, and then washed sequentially with 250 g of 1 normal aqueous hydrochloric acid solution, 250 g of 1 normal sodium hydroxide aqueous solution, and 250 g of distilled water, and then concentrated under reduced pressure to obtain a diacrylonitrile of 3 mol of isosorbide-propylene oxide ( Example A2-1, in the following formula 5-2, in the case of m + n = 3), isosorbide-propylene oxide 5 mol adduct of diacrylonitrile (Example A2-2, in the following formula 5-2, m+n=5), isosorbide-diacrylonitrile of a 10 mole adduct of propylene oxide (Example A2-3, in the following formula 5-2, when m+n=10) and isosorbide- Diacrylonitrile of 25 mol of propylene oxide adduct (in Example A2-4, the following formula 5-2, when m+n=25) was obtained in a yield of 85% to 95%, respectively.

[Formula 5-2]

Example A3-1 to A3-4: isosorbide-ethylene Oxide Adjunct Dicrotononitrile Produce

The isosorbide-ethylene oxide 3 mol adduct (1 mol) prepared in Preparation Examples 1-1 to 1-4, isosorbide-ethylene oxide 5 mol adduct (1 mol), isosorbide-ethylene oxide 10 Each of the molar adduct (1 mole) and the isosorbide-ethylene oxide 25 mole adduct (1 mole) was added to a glass reactor together with 1.5 g (0.01 mole) of 1,8-Diazabicyclo[5.4.0]undec-7-ene. Then, the internal temperature was raised to 70 ~ 75 ℃, and then crotononitrile 201g (3 mol) was slowly added dropwise for about 4 hours so that the internal temperature did not exceed 80 ℃. After the dropwise addition was completed, the mixture was stirred for 3 hours while adjusting the internal temperature to 70-75°C, and then cooled to room temperature. The reaction mixture was diluted with 500 g of ethyl acetate, and then washed sequentially with 250 g of 1 normal hydrochloric acid aqueous solution, 250 g of 1 normal sodium hydroxide aqueous solution, and 250 g of distilled water, and then concentrated under reduced pressure to dicrotononitrile as an adduct of 3 mol of isosorbide-ethylene oxide. (Example A3-1, in the following formula 5-3, in the case of m + n = 3), isosorbide-dicrotononitrile of a 5 mol adduct of ethylene oxide (Example A3-2, in the following formula 5-3 , m+n=5), isosorbide-dicrotononitrile of 10 mole adducts of ethylene oxide (Example A3-3, in the following formula 5-3, when m+n=10) and isosorbide -Dicrotononitrile of 25 mole adduct of ethylene oxide (Example A3-4, in the following formula 5-3, when m+n=25) was obtained in a yield of 85% to 95%, respectively.

[Chemical Formula 5-3]

Example A4-1 to A4-4: isosorbide-ethylene Oxide Adjunct Of dimethacrylonitrile Produce

The isosorbide-ethylene oxide 3 mol adduct (1 mol) prepared in Preparation Examples 1-1 to 1-4, isosorbide-ethylene oxide 5 mol adduct (1 mol), isosorbide-ethylene oxide 10 Each of the molar adduct (1 mole) and the isosorbide-ethylene oxide 25 mole adduct (1 mole) was added to a glass reactor together with 1.5 g (0.01 mole) of 1,8-Diazabicyclo[5.4.0]undec-7-ene. Then, after the internal temperature was raised to 70 ~ 75 ℃ methacrylonitrile 201g (3 mol) was slowly added dropwise for about 4 hours so that the internal temperature did not exceed 80 ℃. After the dropwise addition was completed, the mixture was stirred for 3 hours while adjusting the internal temperature to 70-75°C, and then cooled to room temperature. The reaction mixture was diluted with 500 g of ethyl acetate, and then washed sequentially with 250 g of 1 normal aqueous hydrochloric acid solution, 250 g of 1 normal sodium hydroxide solution, and 250 g of distilled water, and then concentrated under reduced pressure to dimethacrylic acid of 3 mol of isosorbide-ethylene oxide. Nitrile (Example A4-1, in the following formula 5-4, in the case of m+n=3), dimethacrylonitrile of isosorbide-ethylene oxide 5 mol adduct (Example A4-2, the following formula 5- In 4, in the case of m+n=5), dimethacrylonitrile of a 10 mole adduct of isosorbide-ethylene oxide (Example A4-3, in the following formula 5-4, when m+n=10) and Dimethacrylonitrile (in Example A4-4, formula 5-4, m+n=25) of 25 mole adducts of isosorbide-ethylene oxide was obtained in a yield of 85% to 95%.

[Chemical Formula 5-4]

Example A5-1 to A5-4: isosorbide-propylene Oxide Adjunct Of dicinamonitrile Produce

The isosorbide-propylene oxide 3 mole adduct (1 mole) prepared in Preparation Examples 2-1 to 2-4, isosorbide-propylene oxide 5 mole adduct (1 mole), isosorbide-propylene oxide 10 Each of the molar adduct (1 mole) and the isosorbide-propylene oxide 25 mole adduct (1 mole) was added to a glass reactor with 1.5 g (0.01 mole) of 1,8-Diazabicyclo[5.4.0]undec-7-ene. Then, the internal temperature was raised to 70 ~ 75 ℃, and then 387g (3 mol) of cinnamonnitrile was slowly added dropwise for about 4 hours so that the internal temperature did not exceed 80 ℃. After the dropwise addition was completed, the mixture was stirred for 5 hours while adjusting the internal temperature to 70-75°C, and then cooled to room temperature. The reaction mixture was diluted with 500 g of ethyl acetate, washed sequentially with 250 g of 1 normal aqueous hydrochloric acid solution, 250 g of 1 normal sodium hydroxide aqueous solution, and 250 g of distilled water, and then concentrated under reduced pressure, followed by concentration of isosorbide-propylene oxide 3 mol adduct disinamonitrile ( Example A5-1, in the following formula 5-5, in the case of m + n = 3), isosorbide-propylene oxide 5 mol adduct disinamonitrile (in Example A5-2, the following formula 5-5, m + n = 5), isosorbide-propylene oxide 10 mol adduct of disinamonitrile (Example A5-3, in the following formula 5-5, when m + n = 10) and isosorbide-propylene oxide Each of the 25 mole adducts of dicinamonitrile (in Example A5-4, in the following Chemical Formula 5-5, when m+n=25) was obtained in 80% to 90% yield.

[Chemical Formula 5-5]

<Preparation of isosorbide-dicarboxylic acid compound (step (2))>

Example B1-1 to B1-4: isosorbide-ethylene Oxide Adjunct Of diacrylic acid Produce

400 g of purified water was put into a glass reactor, and then 95 g of sodium hydroxide (NaOH) was added to completely dissolve. Thereafter, diacrylonitrile of the isosorbide-ethylene oxide 3 mol adduct of Examples A1-1 to A1-4 (in the above formula 5-1, in the case of m+n=3), isosorbide-ethylene oxide 5 Diacrylonitrile of the molar adduct (in the formula 5-1, in the case of m+n=5), diacrylonitrile of the 10 molar adduct of isosorbide-ethylene oxide (in Formula 5-1, m+n= 10) and diacrylonitrile (in the formula 5-1, in the case of m+n=25) of 25 mol adducts of isosorbide-ethylene oxide were added thereto, followed by reflux stirring for 2 hours. After that, it was cooled to room temperature, and conc. 200 g of HCl was added to adjust the pH of the reaction product to 1 and concentrated. After adding 300 mL of acetone to the concentrate, the mixture was stirred for 2 hours to precipitate sodium chloride (NaCl) and filtered. Thereafter, the filtrate was concentrated to add 3 moles of isosorbide-ethylene oxide, diacrylic acid (Example B1-1, in the following formula 1-1, in the case of m+n=3), and 5 moles of isosorbide-ethylene oxide Diacrylic acid of water (Example B1-2, in the following formula 1-1, in the case of m+n=5), diacrylic acid of 10 mole adducts of isosorbide-ethylene oxide (Example B1-3, following formula 1-1 In the case of m+n=10) and isosorbide-ethylene oxide 25 mole adducts of diacrylic acid (Example B1-4, in the following formula 1-1, m+n=25) were obtained, respectively. At this time, the yield was 91%.

[Formula 1-1]

<Isosorbide- Diester Preparation of compound (step (3))>

Example B2-1 to B2-4: isosorbide-ethylene Oxide Adjunct Of di[methyl(3-methylpropionic acid)] Produce

Dicrotononitrile of 3 mol adducts of isosorbide-ethylene oxide prepared in Examples A3-1 to A3-4 to 1 L of methanol contained in a glass reactor (in Chemical Formula 5-3, in the case of m+n=3), Dicrotononitrile of isosorbide-ethylene oxide 5 mol adduct (in Chemical Formula 5-3, in the case of m+n=5), dicrotononitrile of isosorbide-ethylene oxide 10 mol adduct (Formula 5- In 3, m+n=10) and dicrotononitrile of 25 mole adducts of isosorbide-ethylene oxide (in Chemical Formula 5-3, in the case of m+n=25), after diluting 100 g each, sulfuric acid 20 g was slowly added dropwise. The reaction mixture was stirred under reflux for 5 hours and then cooled to room temperature, and the pH of the reaction mixture was adjusted to between 7 and 9 using 3N sodium hydroxide (NaOH), followed by distillation under reduced pressure. Subsequently, the concentrate was diluted with 500 g of ethyl acetate, washed twice with 100 g of purified water, concentrated under reduced pressure, and di[methyl(3-methylpropionic acid)] of an adduct of 3 mol of isosorbide-ethylene oxide] (Example B2-1, In the following formula 1-2, in the case of m+n=3), isosorbide-ethylene oxide 5 mol adduct of di[methyl(3-methylpropionic acid)] (Example B2-2, in the following formula 1-2, m + n = 5), isosorbide-di[methyl (3-methylpropionic acid) of 10 mol adducts of ethylene oxide] (Example B2-3, in the following formula 1-2, m + n = 10 ) And di[methyl(3-methylpropionic acid)] of 25 mole adducts of isosorbide-ethylene oxide (Example B2-4, in the following formula 1-2, when m+n=25) were obtained, respectively. At this time, the yield was 85%.

[Formula 1-2]

Example B3-1 to B3-4: isosorbide-ethylene Oxide Adjunct Of di[isopropyl(2-methylpropionic acid)] Produce

Dicrotononitrile of the isosorbide-ethylene oxide 3 mol adduct prepared in Examples A3-1 to A3-4 (in Chemical Formula 5-3, in the case of m+n=3), isosorbide-ethylene oxide 5 Dicrotononitrile of the molar adduct (in Formula 5-3, in the case of m+n=5), dicrotononitrile of the 10 molar adduct of isosorbide-ethylene oxide (in Formula 5-3, m+n= 10) and dicrotononitrile of 25 mole adducts of isosorbide-ethylene oxide (in the above formula 5-3, in the case of m+n=25) instead of 100 g each, in Examples A4-1 to A4-4 Dimethacrylonitrile of the prepared isosorbide-ethylene oxide 3 mol adduct (in the above formula 5-4, in the case of m+n=3), dimethacrylonitrile of the isosorbide-ethylene oxide 5 mol adduct ( In Formula 5-4, in the case of m+n=5), dimethacrylonitrile (in the case of m+n=10 in Formula 5-4, in the case of m+n=10) of isosorbide-ethylene oxide 10 mol adduct and isosorb Dimethacrylonitrile of 25 mol of bead-ethylene oxide adduct (in the above formula 5-4, when m+n=25) was used, except that 100 g of each was used, and 1 L of 2-propanol was used instead of 1 L of methanol as the reaction solvent. Then, by performing the same method as in Example B2, isosorbide-ethylene oxide 3 mol adduct of di[isopropyl (2-methylpropionic acid)] (Example B3-1, in the following formula 1-3, m+n =3), isosorbide-ethylene oxide 5 mol adduct of di[isopropyl(2-methylpropionic acid)] (Example B3-2, in the following formula 1-3, when m+n=5), Di[isopropyl(2-methylpropionic acid)] of 10 mole adducts of isosorbide-ethylene oxide (Example B3-3, in the following formula 1-3, when m+n=10) and isosorbide-ethylene oxide Di[isopropyl(2-methylpropionic acid)] of 25 mole adducts (Example B3-4, in the following formula 1-3, when m+n=25) were obtained, respectively. At this time, the yield was 89%.

[Formula 1-3]

Example B4-1 to B4-4: isosorbide-propylene Oxide Adjunct Of di[benzyl(3-phenylpropionic acid)] Produce

Dicrotononitrile of the isosorbide-ethylene oxide 3 mol adduct prepared in Examples A3-1 to A3-4 (in Chemical Formula 5-3, in the case of m+n=3), isosorbide-ethylene oxide 5 Dicrotononitrile of the molar adduct (in Formula 5-3, in the case of m+n=5), dicrotononitrile of the 10 molar adduct of isosorbide-ethylene oxide (in Formula 5-3, m+n= 10) and dicrotononitrile of 25 mole adduct of isosorbide-ethylene oxide (in Chemical Formula 5-3, in the case of m+n=25) prepared in Examples A5-1 to A5-4 instead of 100 g each Isosorbide-propylene oxide 3 mol adduct disinamonitrile (in the above formula 5-5, in the case of m + n = 3), isosorbide-propylene oxide 5 mol adduct disinamonitrile (the above formula 5-5 In, in the case of m+n=5), isosorbide-propylene oxide 10 mol adduct disinamonitrile (in Formula 5-5, when m+n=10) and isosorbide-propylene oxide 25 mol added 100 g of dicinamonitrile of water (in the case of m+n=25 in Formula 5-5 above) was used, 500 mL of tetrahydrofuran and 100 mL of benzyl alcohol were used instead of 1 L of methanol as the reaction solvent, and the reflux stirring time was 5 Di[benzyl(3-phenylpropionic acid)] of isosorbide-propylene oxide 3 mole adduct was carried out in the same manner as in Example B2, except that the time was changed to 18 hours (Example B4-1, the following formula In 1-4, in the case of m+n=3), isosorbide-di[benzyl(3-phenylpropionic acid)] of 5 mole adducts of propylene oxide] (Example B4-2, in the following formula 1-4, m+ n=5), di[benzyl(3-phenylpropionic acid)] of isosorbide-propylene oxide 10 mol adduct (Example B4-3, in the following formula 1-4, when m+n=10) and Di[benzyl(3-phenylpropionic acid)] of 25 mole adducts of isosorbide-propylene oxide (Example B4-4, in the following formula 1-4, when m+n=25) was obtained, respectively. At this time, the yield was 90%.

[Formula 1-4]

Example B5-1 to B5-4: isosorbide-ethylene Oxide Adjunct Of di[phenyl(3-methylpropionic acid)] Produce

Dicrotononitrile of the isosorbide-ethylene oxide 3 mol adduct prepared in Examples A3-1 to A3-4 (in Chemical Formula 5-3, in the case of m+n=3), isosorbide-ethylene oxide 5 Dicrotononitrile of the molar adduct (in Formula 5-3, in the case of m+n=5), dicrotononitrile of the 10 molar adduct of isosorbide-ethylene oxide (in Formula 5-3, m+n= 10) and dicrotononitrile of 25 mole adducts of isosorbide-ethylene oxide (in Chemical Formula 5-3, in the case of m+n=25) prepared in Examples A4-1 to A4-4 instead of 100 g each Dimethacrylonitrile of 3 mol of isosorbide-ethylene oxide adduct (in the above formula 5-4, in the case of m+n=3), dimethacrylonitrile of 5 mol of isosorbide-ethylene oxide adduct (above In Formula 5-4, in the case of m+n=5), dimethacrylonitrile (in the above Formula 5-4, in the case of m+n=10) of 10 mole adducts of isosorbide-ethylene oxide, and isosorbide -Dimethacrylonitrile of 25 mol of ethylene oxide adduct (in the above formula 5-4, in the case of m+n=25), 100 g of each was used, and 500 ml of tetrahydrofuran and 100 ml of phenol were used instead of 1 L of methanol as a reaction solvent. , Except that the reflux stirring time was changed from 5 hours to 24 hours, and isosorbide-propylene oxide 3 mole adduct di[phenyl(3-methylpropionic acid)] by performing the same method as in Example B2] (Example B5-1, in the following formula 1-5, when m+n=3), isosorbide-di[phenyl(3-methylpropionic acid)] of 5 mol adducts of propylene oxide] (Example B5-2, following formula 1 In -5, in the case of m+n=5), di[phenyl(3-methylpropionic acid)] of 10 mole adducts of isosorbide-propylene oxide] (Example B5-3, in the following formula 1-5, m+n = 10) and isosorbide-propylene oxide 25 mole adduct of di[phenyl(3-methylpropionic acid)] (Example B5-4, in the following formula 1-5, when m+n=25) Obtained. At this time, the yield was 74%.

[Formula 1-5]

Example B6-1 to B6-4: isosorbide-ethylene Oxide Adjunct Of di(cyclohexylpropionic acid) Produce

Dicrotononitrile of the isosorbide-ethylene oxide 3 mol adduct prepared in Examples A3-1 to A3-4 (in Chemical Formula 5-3, in the case of m+n=3), isosorbide-ethylene oxide 5 Dicrotononitrile of the molar adduct (in Formula 5-3, in the case of m+n=5), dicrotononitrile of the 10 molar adduct of isosorbide-ethylene oxide (in Formula 5-3, m+n= 10) and dicrotononitrile of 25 mole adducts of isosorbide-ethylene oxide (in Chemical Formula 5-3, in the case of m+n=25) prepared in Examples A1-1 to A1-4 instead of 100 g, respectively Diacrylonitrile of 3 mol of isosorbide-ethylene oxide adduct (in the above formula 5-1, in the case of m+n=3), diacrylonitrile of 5 mol of isosorbide-ethylene oxide adduct (above Formula 5 In -1, when m+n=5), diacrylonitrile of 10 mole adduct of isosorbide-ethylene oxide (in Formula 5-1, when m+n=10) and isosorbide-ethylene oxide Diacrylonitrile (in the above formula 5-1, in the case of m+n=25) of 25 mole adducts, 100 g each, and 500 mL of tetrahydrofuran and 100 mL of cyclohexanol were used instead of 1 L of methanol as a reaction solvent, and reflux Di(cyclohexylpropionic acid) of isosorbide-ethylene oxide 3 mole adduct was carried out in the same manner as in Example B2, except that the stirring time was changed from 5 hours to 18 hours (Example B6-1, the following formula In 1-6, in the case of m+n=3), di(cyclohexylpropionic acid) of 5 mole adducts of isosorbide-ethylene oxide (Example B6-2, in the following formula 1-6, m+n=5) Case), di(cyclohexylpropionic acid) of the adduct of 10 moles of isosorbide-ethylene oxide (Example B6-3, in the following formula 1-6, when m+n=10) and 25 moles of isosorbide-ethylene oxide Each of the adducts di(cyclohexylpropionic acid) (in Example B6-4, formula 1-6 below, in the case of m+n=25) was obtained. At this time, the yield was 89%.

[Formula 1-6]

< Example Antibacterial activity of the compounds of B1 to B6 and Antifungal Test>

[Production Example C1]

Strain culture (activation)

Before proceeding with the antibacterial and antifungal tests, culture was performed several times to increase the activity of the bacteria.

Bacteria are streaked on Nutrient Agar (NA) plates having the components and contents shown in Table 1 below, and then cultured in an incubator at 37°C until colonies are identified, and colonies randomly selected after confirming the presence or absence of contamination of the colonies. Was further cultured under the same conditions to increase the activity of the bacteria.

The fungi are streaked on a Potato Dextrose Agar (PDA) plate having the components and contents shown in Table 2 below and cultured in an incubator at 30°C until growth is confirmed, and then the presence or absence of contamination is checked, and the randomly selected colonies are again under the same conditions. Incubated to increase the activity of the bacteria.

Anhydrosugar Alcohol nucleus and alkylene Oxide Extension Branched Dicarboxyl Preparation of compound-containing culture solution

After preparing a liquid medium according to the type of strain, 0.5% by weight, 0.7% by weight, 1% by weight, 1.2% by weight, 1.5% by weight and 2% by weight of the compounds prepared in Examples B1 to B6 were added to each liquid medium. Was added so that

For bacteria, Tryptic Soy Broth (TSB) having the components and contents of Table 3 below was used as a liquid medium, and for fungi, Potato Dextrose Broth (PDB) having the components and contents of Table 4 below was used as the liquid medium. A liquid medium containing an anhydrosugar alcohol nucleus and a branched dicarboxyl compound having an alkylene oxide extension was prepared by dispensing into a 14 ml test tube.

inoculation Bacteria Preparations

Each colony activated by culturing on the Agar plate was used as an inoculum for inoculation into the culture medium containing the compound prepared in Examples B1 to B6 after checking for additional external contamination by identifying morphological characteristics. Each strain was diluted in 9 ml of physiological saline by dipping colonies using platinum. The dilution concentration at this time was adjusted to a value of McFarland standard 0.5. When the value of the McFarland standard of 0.5 was adjusted, the concentration of cells in physiological saline was 1.5 x 10 ⁸ CFU/ml.

Inoculation and culture

In each of the 3 ml of the medium containing the compounds prepared in Examples B1 to B6 for each concentration, 30 μl of each culture solution was added, and the culture solution was diluted 1/100 and inoculated. The inoculated bacteria were cultured at 37°C for 24 hours at 200 rpm, and the inoculated fungi were cultured at 30°C for 72 hours at 200 rpm.

Confirmation of growth of inoculated cells (preliminary test)

In order to simply check the growth of the cells in the inoculated culture medium, streaking was performed on the Agar plate. After streaking a part of the bacterial culture medium cultured for 24 hours using platinum and a part of the fungal culture medium cultured for 72 hours on Tryptic Soy Agar (TSA) plate and Potato Dextrose Agar (PDA) plate, respectively, 37°C and 30°C, respectively. Incubated until the growth of the bacteria was confirmed. Specifically, when the bacteria were cultured for 24 hours, the growth of the bacteria could be confirmed, and when the fungi were cultured for 72 hours, the growth of the bacteria could be confirmed. After streaking, it was possible to simply check the presence or absence of growth by culturing, and the concentration of the compounds prepared in Examples B1 to B6 could be reset.

Minimum growth arrest concentration ( MIC ) Judgment

An experiment was conducted to set the minimum growth inhibition concentration (MIC) based on the concentration set through the preliminary test. The bacteria solution was inoculated into the liquid medium containing the compounds prepared in Examples B1 to B6 at a set concentration. The liquid medium containing the compounds prepared in Examples B1 to B6 was carried out by placing 3 ml in a 14 ml test tube, and the inoculation bacteria solution was prepared and used in the same manner as in the above-described inoculation bacteria solution preparation (1.5 in physiological saline solution). Prepare a bacterial solution to a concentration of x 10 ⁸ CFU/ml). 30 μl of bacterial solution in liquid medium After inoculation, bacteria were cultured at 37°C for 24 hours, and fungi were cultured at 30°C for 72 hours. After cultivation, the culture solution was plated on an Agar plate to check the growth of bacteria. Specifically, bacteria were plated on Nutrient Agar (NA) plate, and fungi were plated on Potato Dextrose Agar (PDA) plate, and then colony formation was confirmed unlike preliminary tests. After plating and culturing for each concentration, the concentration when no colonies were formed was set as the minimum growth inhibition concentration (MIC).

[Example C1] Preliminary test of 3 bacteria and 2 fungi

As three kinds of bacteria, Pseudomonas aeruginosa KCTC 2513, Staphylococcus aureussubsp. aureus KCTC 3881 and Escherichia coli were used, and after their activation, bacterial solutions were prepared according to McFarland standard 0.5. The bacterial solution was inoculated into Tryptic Soy Broth to which the compounds prepared in Examples B1 to B6 were added, and cultured at 30° C. at 200 rpm for 24 hours. After streaking the culture medium cultured for 24 hours on a Nutrient Agar (NA) plate, whether or not growth by concentration (the concentration is the weight% of the compound prepared in Examples B1 to B6 based on the total 100% by weight of the culture medium) Confirmed.

Candida albicans and Aspergillus niger were used as two types of fungi, and after their activation, a bacterial solution was prepared according to McFarland standard 0.5. The bacterial solution was inoculated into Potato Dextrose Broth to which the compounds prepared in Examples B1 to B6 were added, and cultured at 30° C. at 200 rpm for 72 hours. After streaking the culture solution cultured for 72 hours on a Potato Dextrose Agar plate, it was confirmed whether or not growth by concentration (the concentration is the weight% of the compound prepared in Examples B1 to B6 based on the total 100% by weight of the culture solution). .

As a result, as can be seen from Tables 5 to 14 below, the compounds prepared in Examples B1 to B6 have antibacterial activity against 3 types of bacteria and against 2 types of fungi regardless of high and low concentrations across various substituent structures. Showed antifungal activity.

[Example C2] MIC test of 3 bacteria and 2 fungi

Based on the preliminary test result of Example C1, the concentration range of the compounds prepared in Examples B1 to B6 was set to perform the MIC test. The concentration range of the compounds prepared in Examples B1 to B6 was set to 5,000 to 20,000 ppm, and then the experiment was conducted (the MIC test was performed in ppm units with reference to the concentration (% by weight) range of the preliminary test). MIC test results, depending on the strain and the compound prepared in Examples B1 to B6, as shown in Table 15 below, exhibits excellent antibacterial activity in the presence of the compound prepared in Examples B1 to B6 at least 5,000 ppm or more, at least 5,000 ppm It was confirmed that the compounds prepared in Examples B1 to B6 showed excellent antifungal activity in the presence of the compounds.

Claims (26)

Compound represented by the following formula A:
[Formula A]
XYOMO-Y'-X
In Formula A,
X is -COOR ₄ , wherein each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,
Y is *-[CH ₂ CHR ₁ O] _m -CHR ₂ CHR ₃ -, and
Y'is *-[CH ₂ CHR ₁ O] _n -CHR ₂ CHR ₃ -,
However, * is a site bonded to O,
Wherein each R ₁ is independently hydrogen, alkyl or aryl,
R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,
m and n are each independently an integer of 0 to 15,
m+n is an integer from 1 to 25,
M is a divalent organic group derived from anhydrosugar alcohol. The compound of claim 1, wherein M is a divalent organic group derived from isosorbide, isomannide, or isoidide. The compound of claim 1, wherein M is selected from the following formula:

The compound of claim 1, represented by the following Formula 1:
[Formula 1]

In Formula 1,
Each R ₁ is independently hydrogen, alkyl or aryl,
R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,
Each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,
m and n are each independently an integer of 0 to 15,
m+n is an integer from 1 to 25. The compound of claim 1, represented by the following Formula 2:
[Formula 2]

In Chemical Formula 2,
Each R ₁ is independently hydrogen, alkyl or aryl,
R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,
Each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,
m and n are each independently an integer of 0 to 15,
m+n is an integer from 1 to 25. The compound of claim 1, represented by the following formula (3):
[Formula 3]

In Chemical Formula 3,
Each R ₁ is independently hydrogen, alkyl or aryl,
R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,
Each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,
m and n are each independently an integer of 0 to 15,
m+n is an integer from 1 to 25. (1) performing Michael reaction of anhydrosugar alcohol-alkylene oxide adduct and a nitrile compound; And
(2) comprising the step of adding sodium hydroxide or alcohol to the compound obtained from the Michael reaction,
Method for producing a compound represented by formula A:
[Formula A]
XYOMO-Y'-X
In Formula A,
X is -COOR ₄ , wherein each R ₄ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl,
Y is *-[CH ₂ CHR ₁ O] _m -CHR ₂ CHR ₃ -, and
Y'is *-[CH ₂ CHR ₁ O] _n -CHR ₂ CHR ₃ -,
However, * is a site bonded to O,
Wherein each R ₁ is independently hydrogen, alkyl or aryl,
R ₂ and R ₃ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl,
m and n are each independently an integer of 0 to 15,
m+n is an integer from 1 to 25,
M is a divalent organic group derived from anhydrosugar alcohol. The method of claim 7, wherein M is a divalent organic group derived from isosorbide, isomannide, or isoidide. The method of claim 7, wherein M is selected from the following formulae:

The method of claim 7, further comprising the step of adding an alkylene oxide to both ends of the anhydrosugar alcohol before step (1). The method of claim 10, wherein 1 to 30 molar equivalents of alkylene oxide are added to 1 molar equivalent of anhydrosugar alcohol. The method of claim 7, wherein the nitrile compound of step (1) is acrylonitrile, methacrylonitrile, crotononitrile, cinnamonitrile, 3-(furan-2-yl)prop-2-ennitrile, cyclohexane A method for producing a compound represented by formula A, selected from the group consisting of acrylonitrile or a combination thereof. The method of claim 7, wherein the reaction is performed in a ratio of 1 to 10 molar equivalents of a nitrile compound to 1 molar equivalent of an anhydrosugar alcohol-alkylene oxide adduct in step (1). The method of claim 7, wherein the Michael reaction is carried out in the presence of 0.005 to 0.05 molar equivalent of a base catalyst with respect to 1 molar equivalent of anhydrosugar alcohol-alkylene oxide adduct in step (1). . The method of claim 7, wherein the alcohol in step (2) is selected from methanol, 2-propanol, benzyl alcohol, phenol, cyclohexanol, or a mixture thereof. The method according to claim 7, wherein 50 to 150 g of sodium hydroxide or 0.05 to 2 L of alcohol is added to 100 g of the compound obtained from the Michael reaction in step (2). An antimicrobial composition comprising a compound represented by Formula A according to any one of claims 1 to 6. The antimicrobial composition of claim 17, wherein the content of the compound represented by Formula A is 0.005 to 30% by weight based on 100% by weight of the antimicrobial composition. The method of claim 17, wherein phenoxyethanol, alkanediol, methylchloroisothiazolinone, methylisothiazolinone, benzoic acid or a salt thereof, a benzoic acid ester derivative, salicylic acid or a salt thereof, 4-hydroxy benzoic acid or a salt thereof, sor The group consisting of brolic acid or its salt, dehydroacetic acid or its salt, dehydroacetic acid ester derivative, benzyl alcohol, 2-methylisothiazole-3(2H)-one, 4-isopropyl-m-cresol or zinc pyrithione The antimicrobial composition further comprises one or more additives selected from. An antifungal composition comprising a compound represented by Formula A according to any one of claims 1 to 6. The antifungal composition according to claim 20, wherein the content of the compound represented by Formula A is 0.005 to 30% by weight, based on 100% by weight of the antifungal composition. The method of claim 20, wherein phenoxyethanol, alkanediol, methylchloroisothiazolinone, methylisothiazolinone, benzoic acid or a salt thereof, a benzoic acid ester derivative, salicylic acid or a salt thereof, 4-hydroxy benzoic acid or a salt thereof, sor The group consisting of brolic acid or its salt, dehydroacetic acid or its salt, dehydroacetic acid ester derivative, benzyl alcohol, 2-methylisothiazole-3(2H)-one, 4-isopropyl-m-cresol or zinc pyrithione An antifungal composition further comprising one or more additives selected from. A formulation comprising the antimicrobial composition according to claim 17. The formulation according to claim 23, wherein the formulation is selected from the group consisting of cosmetics, skin care agents, detergents, colorants, paints, or plant protectants. A formulation comprising the antifungal composition according to claim 20. The formulation according to claim 25, wherein the formulation is selected from the group consisting of cosmetics, skin care agents, detergents, colorants, paints, or plant protectants.