KR20190083976A - Branched dicarboxylic compound having anhydrosugar alcohol core and side chains and method for preparing the same - Google Patents

Abstract

The present invention relates to a branched dicarboxylic compound having an anhydrosugar alcohol nucleus and a method for manufacturing the same. More specifically, the present invention relates to: the branched dicarboxylic compound having the anhydrosugar alcohol nucleus manufactured by conducting a reaction with a nitrile compound and adding sodium hydroxide or alcohol, having renewable plant-based anhydrosugar alcohol as a raw material and also being used as monomers of polymer condensation polymerization or as antibacterial and/or antifungal agents; and the method for manufacturing the same.

Description

BACKGROUND OF THE INVENTION 1. Field of the Invention [0001] The present invention relates to a branched dicarboxylic compound having an alcohol-free alcoholic nucleus and a process for producing the same. BACKGROUND ART < RTI ID = 0.0 >

The present invention relates to a branched dicarboxylic compound having an alcohol-free alcoholic nucleus and a method for producing the same. More particularly, the present invention relates to a method for producing a branched dicarboxylic compound having an anhydride alcohol nucleus by reacting with a nitrile compound, To a branched dicarboxylic compound having an anhydride alcohol nucleus, which can be used as a monomer for polymer condensation polymerization or as an antimicrobial agent and / or an antifungal agent, and a process for producing the same.

Hydrogenated sugar (also referred to as " sugar alcohol ") refers to a compound obtained by adding hydrogen to a reducing end group of a saccharide, 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 (C 4, 5, 6 and 7, respectively), depending on 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 useful substances.

Anhydrosugar alcohol has a diol form with two hydroxyl groups in the molecule and can be prepared by utilizing hexitol derived from starch (for example, Korean Patent No. 10-1079518, Korean Patent Laid- -2012-0066904). Since alcohol-free alcohol is an eco-friendly substance derived from renewable natural resources, there has been much interest for a long time and studies on the manufacturing method have been carried out. Among these alcohol-free alcohols, isosorbide prepared from sorbitol has the widest industrial application currently.

The use of anhydrous alcohol is widely used in the treatment of cardiovascular diseases, patches, adhesives, oral cleansers and the like, solvents for compositions in the cosmetics industry, and emulsifiers in the food industry. In addition, it is possible to increase the glass transition temperature of a polymer substance such as polyester, PET, polycarbonate, polyurethane, and epoxy resin, to improve the strength of these materials, and to be an environmentally friendly material derived from natural materials. useful. It is also known to be used as an environmentally friendly solvent for adhesives, environmentally friendly plasticizers, biodegradable polymers, and water-soluble lacquers.

In this connection, International Patent Publication No. 2013-173020 discloses a dicarboxylic acid substance having isosorbide nucleus and a method for producing the same, but it is expensive to manufacture by using an expensive raw material (triflic anhydride) There is a problem that commercial production is difficult using an acid component in the step of converting a nitrile functional group into a carboxylic acid.

Accordingly, there is a need for a branched dicarboxylic compound having an alcohol-free alcoholic nucleus and a method for producing the same, which can be manufactured at low cost, can simplify the manufacturing process, and is easy to produce for commercial purposes, compared with the conventional production methods.

It is an object of the present invention to provide a method for producing an antifungal agent which can be used as a monomer for polymer condensation polymerization or as an antimicrobial agent and / or an antifungal agent, which is prepared by reacting a nitrate compound with a nitril compound and adding sodium hydroxide or alcohol, , A branched dicarboxylic compound having an alcohol-free alcohol nucleus, and a process for producing the same.

In order to solve the above-mentioned technical problems, the present invention provides a compound represented by the following formula (A)

(A)

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

In the above formula (A)

X is -COOR _3, where R ₃ is independently, hydrogen, alkyl, aryl, arylalkyl or cycloalkyl each,

Y is -CR ₁ HCR ₂ H-, wherein R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, Aryl or cycloalkyl,

M is a divalent organic group derived from anhydrous alcohol.

According to another aspect of the present invention, there is provided a process for preparing a nitrile compound, comprising: (1) performing a Michael reaction of an alcohol with no alcohol and a nitrile compound; And (2) adding sodium hydroxide or an alcohol to the compound obtained from the Michael reaction.

(A)

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

In the above formula (A)

X is -COOR _3, where R ₃ is independently, hydrogen, alkyl, aryl, arylalkyl or cycloalkyl each,

Y is -CR ₁ HCR ₂ H-, wherein R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, Aryl or cycloalkyl,

M is a divalent organic group derived from anhydrous alcohol.

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

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

According to another aspect of the present invention, there is provided a formulation comprising the antimicrobial composition according to the present 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 dicarboxylic compound having an alcohol-free alcoholic nucleus of the present invention is produced through the reaction with a nitrile compound and the addition of sodium hydroxide or alcohol using a regenerable plant-based, anhydrous alcohol as a raw material, And the production process can be simplified, and the commercial production is easy using the base component in the step of converting the nitrile functional group into the carboxylic acid.

In addition, since the antimicrobial composition and the antifungal composition of the present invention comprise a branched dicarboxylic compound having an anhydrosugar alcohol nucleus showing excellent effects on the inhibition of the growth of microorganisms including bacteria and fungi, , A skin-beauty agent, a detergent, a coloring agent, a paint, and a plant protection agent.

Hereinafter, the present invention will be described in detail.

The present invention provides compounds represented by formula (A)

(A)

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

In the above formula (A)

X is -COOR _3, where R ₃ is independently, hydrogen, alkyl, aryl, arylalkyl or cycloalkyl each,

Y is -CR ₁ HCR ₂ H-, wherein R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, Aryl or cycloalkyl,

M is a divalent organic group derived from anhydrous alcohol.

The anhydrosugar alcohol is prepared from a hydrogenated sugar derived from a natural product.

Hydrogenated sugar (also referred to as " sugar alcohol ") refers to a compound obtained by adding hydrogen to a reducing end group of a saccharide, 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 (C 4, 5, 6 and 7, respectively), depending on 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 useful substances.

Anhydrosugar alcohol has a diol form with two hydroxyl groups in the molecule and can be prepared by utilizing hexitol derived from starch (for example, Korean Patent No. 10-1079518, Korean Patent Laid- -2012-0066904). Since alcohol-free alcohol is an eco-friendly substance derived from renewable natural resources, there has been much interest for a long time and studies on the manufacturing method have been carried out. Among these alcohol-free alcohols, isosorbide prepared from sorbitol has the widest industrial application currently.

In the compound represented by the general formula (A) of the present invention, M is isosorbide (1,4-3,6-dianhydroisorbitol), isanhydride (1,4-3,6-dianhydro- mannitol) Or a dihydric organic group derived from isoided (1,4-3,6-dianhydroiditol), and in one embodiment, M may be selected from the following formula:

In the compounds represented by formula (A) of the present invention, X is -COOR ₃ , wherein each R ₃ is independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl, Y is -CR ₁ HCR ₂ H-, Wherein R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, aryl, heteroaryl or cycloalkyl.

The alkyl is, for example, substituted or unsubstituted linear alkyl of 1 to 10 (more particularly 1 to 6) carbon atoms; Or a substituted or unsubstituted branched alkyl having 3 to 10 (more specifically 3 to 6) carbon atoms, and the aryl is, for example, a substituted or unsubstituted C6 to C14 (more specifically 6 to 12 ) Monocyclic aryl, polycyclic aryl, or fused cyclic aryl. The arylalkyl may be substituted or unsubstituted arylalkyl of 7 to 24 (more specifically 7 to 18) carbon atoms, and the cycloalkyl may be substituted or unsubstituted, for example, having 3 to 8 carbon atoms Lt; / RTI > may be 3 to 6) cycloalkyl. Also, the heteroaryl is a substituted or unsubstituted 5 to 12-membered (more specifically 5 to 10-membered) monocyclic heteroaromatic ring containing one or more heteroatoms selected from N, O, Aryl, polycyclic heteroaryl, or fused cyclic heteroaryl.

These groups may be substituted with at least one substituent selected from alkyl having 1 to 10 carbon atoms (e.g., methyl, ethyl, propyl, butyl, etc.) or aryl having 6 to 10 carbon atoms (e.g., phenyl, benzyl, .

In one embodiment, the compound represented by formula (A) of the present invention may be a compound represented by formula (1): < EMI ID =

[Chemical Formula 1]

In Formula 1,

R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, aryl, heteroaryl or cycloalkyl,

R < ₃ > are each independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl.

In one embodiment, the compound represented by the formula (A) of the present invention may be a compound represented by the following formulas (1-1) to (1-8).

[Formula 1-1]

[Formula 1-2]

[Formula 1-3]

[Formula 1-4]

[Formula 1-5]

[Chemical Formula 1-6]

[Chemical Formula 1-7]

[Chemical Formula 1-8]

In one embodiment, the compound represented by formula (A) of the present invention may be a compound represented by formula (2): < EMI ID =

(2)

In Formula 2,

R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, aryl, heteroaryl or cycloalkyl,

R < ₃ > are each independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl.

In one embodiment, the compound represented by the formula (A) of the present invention may be a compound represented by the following formulas (2-1) to (2-8).

[Formula 2-1]

[Formula 2-2]

[Formula 2-3]

[Chemical Formula 2-4]

[Chemical Formula 2-5]

 [Chemical Formula 2-6]

[Chemical Formula 2-7]

[Chemical Formula 2-8]

In one embodiment, the compound represented by formula (A) of the present invention may be a compound represented by formula (3): < EMI ID =

(3)

In Formula 3,

R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, aryl, heteroaryl or cycloalkyl,

R < ₃ > are each independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl.

In one embodiment, the compound represented by the formula (A) of the present invention may be a compound represented by the following formulas (3-1) to (3-8).

[Formula 3-1]

[Formula 3-2]

[Formula 3-3]

[Chemical Formula 3-4]

[Formula 3-5]

[Chemical Formula 3-6]

[Chemical Formula 3-7]

[Chemical Formula 3-8]

According to another aspect of the present invention, there is provided a process for preparing a nitrile compound, comprising: (1) performing a Michael reaction of an alcohol with no alcohol and a nitrile compound; And (2) adding sodium hydroxide or an alcohol to the compound obtained from the Michael reaction.

(A)

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

In the above formula (A)

X is -COOR _3, where R ₃ is independently, hydrogen, alkyl, aryl, arylalkyl or cycloalkyl each,

Y is -CR ₁ HCR ₂ H-, wherein R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, Aryl or cycloalkyl,

M is a divalent organic group derived from anhydrous alcohol.

The nitrile compound used in step (1) of the production method of the present invention includes crotononitrile, methacrylonitrile, cinnamonitrile, 3- (furan-2-yl) prop- Nitrile, or a combination thereof. However, the present invention is not limited thereto.

In the above step (1), the reaction may be carried out in an equivalent ratio of 1.5 to 3 molar equivalents of nitrile compound to 1 molar equivalent of alcohol free alcohol. When the molar equivalent of the nitrile compound is too low, the yield of the compound represented by the formula (A) is lowered. On the other hand, when the molar equivalent is too high, an additional effect is not expected and the manufacturing cost is increased.

The Michael reaction can be carried out in the presence of a base catalyst, and the Michael reaction can be carried out in the presence of 0.005 to 0.05 molar equivalent of a base catalyst per 1 molar equivalent of an alcohol without anhydride. If the content of the base catalyst is too low, the reaction rate of the Michael reaction becomes slow. On the other hand, if the content of the base catalyst is too high, it is difficult to expect an additional effect and the manufacturing cost increases.

Examples of the base catalyst include, but are not particularly limited to, hydroxides of alkali metals (specifically, hydroxides of Li, Na, K, Rb or Cs etc.), hydroxides of alkaline earth metals (specifically, Mg, Ca, Sr (Specifically, a carbonate of Li, Na, K, Rb or Cs), an alcoholate of an alkali metal or an alkaline earth metal (specifically, sodium methylate, sodium ethylate or potassium hydroxide) t-butylate, etc.) or basic organic catalysts (specifically, 1,8-diazabicyclo [5.4.0] undec-7-ene ), 4- (dimethylamino) pyridine, etc.), and preferably a basic organic catalyst can be used. When a basic organic catalyst is used as a base catalyst, the rate of Michael reaction (acrylonitrile addition reaction) is accelerated as compared with that of a basic inorganic catalyst, and the problem of serious heat generation due to accumulation of unreacted raw materials upon addition of acrylonitrile compound can be solved .

In the step (1) of performing the Michael reaction of the anhydride alcohol with the nitrile compound, the Michael reaction product may be stirred for 1 to 10 hours. If the stirring time is too short, the yield of the compound represented by the formula (A) can be lowered, and conversely, if the stirring time is too long, no additional effect is expected.

The product of the Michael reaction can be cooled to room temperature after the stirring step and the product of the cooled Michael reaction is reacted with an organic solvent (for example, ethyl acetate, dichloromethane, 2-methyltetrahydrofuran, diethyl ether, etc.) After dilution, it may be sequentially washed with an aqueous solution of hydrochloric acid, an aqueous solution of sodium hydroxide and distilled water. Thereafter, a step of concentration under reduced pressure can be further carried out.

In one embodiment, the compound obtained from step (1) of carrying out the Michael reaction of anhydrosugar alcohol with a nitrile compound can be an anhydrosugar alcohol-dinitrile compound, such as isosorbide (ISB) -dinitrile Lt; / RTI >

[Chemical Formula 4]

In Formula 4,

R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, aryl, heteroaryl or cycloalkyl.

In one embodiment, the compound represented by the general formula (4) of the present invention may be a compound represented by the following general formulas (4-1) to (4-3).

[Formula 4-1]

[Formula 4-2]

[Formula 4-3]

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 may be a substituted or unsubstituted (specifically, an alkyl group having 1 to 10 carbon atoms (Such as methyl, ethyl, propyl, butyl and the like), a cycloalkyl group having 3 to 10 carbon atoms (such as cyclohexyl) or an aryl group having 6 to 10 carbon atoms Substituted or unsubstituted) aliphatic or aromatic alcohols can be used, and those selected from methanol, 2-propanol, benzyl alcohol, phenol, cyclohexanol or mixtures thereof can be used.

In 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 the 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- Dicarboxylic acid compound or ISB-diester compound.

In one embodiment, in step (2), if sodium hydroxide is added, the step of cooling to room temperature is followed by a reflux stirring step followed by a conc. HCl may be added to lower the pH (e. G., To a pH of 1-3), followed by concentration. After the concentration step, acetone, tetrahydrofuran, acetonitrile or the like is added as a salt extraction solvent, and the mixture is stirred to remove salts and filtrate. Thereafter, the filtrate is concentrated to obtain an anhydrosugar alcohol-dicarboxylic acid compound , An ISB-dicarboxylic acid compound) can be obtained.

In one embodiment, in the step (2), when an alcohol is added, a reflux stirring step is performed after dropping an acid component (for example, sulfuric acid, phosphoric acid, hydrochloric acid, etc.) And the basic component (for example, a hydroxide of an alkali metal or an alkaline earth metal such as sodium hydroxide, potassium hydroxide, lithium hydroxide and the like) is added to adjust the pH to 7 to 9, and then the reduced pressure distillation can be performed. Then, the concentrate is diluted with an organic solvent (for example, ethyl acetate, dichloromethane, 2-methyltetrahydrofuran, diethyl ether, etc.), washed with purified water at least once, and then concentrated under reduced pressure, A diester compound (for example, an ISB-diester compound) can be obtained. The content of the basic component is not particularly limited, but is preferably 1N to 5N. If the content of the basic component is too low, the reaction rate becomes slow. On the contrary, if the content is too high, it is difficult to expect further effect, and the 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 the formula (A) can be lowered, and conversely, if the stirring time is too long, no additional effect is expected.

The compound represented by the 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 the above-mentioned formula (A).

The antimicrobial composition of the present invention and the compound represented by the general formula A contained in the antifungal composition are produced from a low cost raw material based on a renewable plant and exhibit excellent effects on the inhibition of the growth of microorganisms including bacteria and fungi, Can be used as an antiseptic. The compositions of the present invention exhibit not only antibacterial properties but also antifungal properties, so that they can be used in various formulations.

The content of the compound represented by the formula (A) contained 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 the formula (A) is 0.005 wt% or more, 0.007 wt% or more, 0.01 wt% or more, 0.012 wt% or more, 0.015 wt% or more, or 0.02 wt% or more At least 0.05% by weight, at least 0.1% by weight, at least 0.5% by weight, at least 0.7% by weight, at least 1% by weight, at least 1.2% by weight, at least 1.5% by weight, at least 2% by weight, at least 3% , At least 7 wt%, at least 10 wt%, at least 15 wt%, or at least 20 wt%. The upper limit of the content of the compound represented by the 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 , 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 the formula (A) is lower than the above-mentioned range, the effect of inhibiting the growth of microorganisms (specifically bacteria) may be insignificant. On the contrary, when the content is higher than the above-mentioned range, no further effect can be obtained.

The antimicrobial composition of the present invention can be used as an antimicrobial composition containing at least one compound selected from the group consisting of phenoxyethanol, alkanediol, methylchloroisothiazolinone, methylisothiazolinone, benzoic acid or its salt, benzoic acid ester derivative, salicylic acid or its salt, (4-isopropyl-4-methylphenyl) carbonate, sorbic acid or a salt thereof, dehydroacetic acid or a salt thereof, a dehydroacetic acid ester derivative, benzyl alcohol, 2-methylisothiazol- Lt; RTI ID = 0.0 > additive < / RTI > The content of the additive may be 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 and 20% by weight or more based on 100% by weight of the antimicrobial composition Or 30 wt% or more, and 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 amount of the compound represented by the formula (A) contained 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 the formula (A) is 0.005 wt% or more, 0.007 wt% or more, 0.01 wt% or more, 0.012 wt% or more, 0.05 wt% or more, 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, 15 wt% or more, or 20 wt% or more. The upper limit of the content of the compound represented by the 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, 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 the formula (A) is lower than the above-mentioned range, the effect of inhibiting the growth of microorganisms (specifically, fungi) may be insignificant. On the contrary, when the content is higher than the above-mentioned range, no further effect can be obtained.

The antifungal composition of the present invention may be used in combination with at least one compound selected from the group consisting of phenoxyethanol, alkanediol, methylchloroisothiazolinone, methylisothiazolinone, benzoic acid or its salt, benzoic acid ester derivative, salicylic acid or its salt, 4-hydroxybenzoic acid or its salt Dihydroacetic acid ester derivatives, benzyl alcohol, 2-methylisothiazol-3 (2H) -one, 4-isopropyl-m-cresol or zinc pyrithione And at least one additive selected from the group consisting of The content of the additive may be 0.1 to 50% by weight, for example, 0.5% by weight to 1% by weight, 5% by weight to 10% by weight and 20% by weight to 100% by weight based on 100% by weight of the antifungal composition, Or less, 30 weight% or less, 45 weight% or less, 40 weight% or less, 35 weight% or less, 30 weight% or less, 20 weight% or 15 weight% or less.

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

The antimicrobial compositions and antifungal compositions of the present invention have excellent effects on inhibition of microbial growth through the measurement of minimal inhibitory concentration (MIC) for a number of bacteria and fungi as described in the Examples below It can be included as a preservative in various products. Agents comprising the antimicrobial compositions, antifungal compositions or combinations thereof of the present invention may be preparations selected from the group consisting of, for example, cosmetics, skin aesthetics, detergents, colorants, paints or plant protectants, It does not.

Hereinafter, the present invention will be described in more detail with reference to examples and comparative examples. However, the scope of the present invention is not limited thereto.

[ Example ]

< ISB - Dinitrile  Preparation of compound (compound of formula 4) (step (1) &gt;

Manufacturing example  1: isosorbide- Diketononitrile  Produce

10 g (0.068 mol, 0.01 eq.) Of 1,8-Diazabicyclo [5.4.0] undec-7-ene were placed in a glass reactor and the internal temperature was adjusted to 70-75 DEG C After completely dissolving the isosorbide, 1,140 g (17 mol, 2.5 eq.) Of crotononitrile was slowly added dropwise for about 4 hours so that the internal temperature did not exceed 80 캜. After completion of dropwise addition, the mixture was stirred for 3 hours while keeping the internal temperature at 70 to 75 ° C, and then cooled to room temperature. The reaction mixture was diluted with 4 kg of ethyl acetate, washed sequentially with 2 kg of 1N hydrochloric acid aqueous solution, 2 kg of 1N sodium hydroxide aqueous solution and 2kg of distilled water, and concentrated under reduced pressure to obtain isosorbide-diketonitrile 1,750 g. The yield was 92%.

[Formula 4-1]

^{1 H NMR (δ ppm; DMSO-} d 6): 1.18 (3H, d), 1.21 (3H, d), 2.35 (1H, dd), 2.39 (1H, dd), 2.66 (1H, dd), 2.70 ( (1H, dd), 3.00 (1H, m), 3.12 (1H, m), 3.49 , 4.01 (1H, dd), 4.01 (1H, d), 4.09

MS ( m / e ): 280

Manufacturing example  2: Isosorbide- Of methacrylonitrile  Produce

(17 mol, 2.5 eq.) Of methacrylonitrile instead of 1,140 g (17 mol, 2.5 eq.) Of crotononitrile was used instead of 1,140 g (17 mol, 2.5 eq.) Of crotononitrile. 1,710 g of bead-dimethacrylonitrile was obtained. The yield was 91%.

[Formula 4-2]

^{1 H NMR (δ ppm; DMSO-} d 6): 1.41 (3H, d), 1.43 (3H, d), 2.99 (1H, m), 3.04 (1H, m), 3.49-3.64 (6H, m), (1H, dd), 3.91 (1H, dd), 3.91 (1H, dd)

MS ( m / e ): 280

Manufacturing example  3: Isosorbide- Dicyanonitrile  Produce

Except that 2,196 g (17 mol, 2.5 eq.) Of cinnamonitrile was used instead of 1,140 g (17 mol, 2.5 eq.) Of crotononitrile, and stirring time after dropwise addition was changed from 3 hours to 6 hours. 2,500 g of isosorbide-dicyanomonitrile of the following formula 4-3 was obtained. The yield was 91%.

[Formula 4-3]

^{1 H NMR (δ ppm; DMSO-} d 6): 2.74 (1H, dd), 2.80 (1H, dd), 2.99 (1H, dd), 3.07 (1H, dd), 3.48 (1H, m), 3.53 ( (1H, dd), 3.76 (1H, dd), 3.80 (1H, dd) , t), 4.29 (1H, t), 7.18-7.40 (10H, m)

MS ( m / e ): 404

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

Example  A1: Isosorbide- Of di (3-methylpropionic acid)  Produce

400 g of purified water was placed in a glass reactor, and then 95 g of sodium hydroxide (NaOH) was added to dissolve completely. Then, 100 g of the isosorbide-dichlorononitrile of Preparation Example 1 was added, and the mixture was refluxed and stirred for 2 hours. Thereafter, the mixture was cooled to room temperature and conc. 200 g of HCl was added to adjust the pH of the reaction solution to 1, and the mixture was concentrated. 300 ml of acetone was added to the concentrate, followed by stirring for 2 hours to precipitate sodium chloride (NaCl). Thereafter, the filtrate was concentrated to obtain isosorbide-di (3-methylpropionic acid) represented by the following formula 1-1. The yield was 92%.

[Formula 1-1]

^{1 H NMR (δ ppm; DMSO-} d 6): 1.19 (3H, d), 1.21 (3H, d), 2.22 (1H, dd), 2.29 (1H, dd), 2.48 (1H, dd), 2.54 ( (1H, dd), 3.47 (1H, m), 3.53 (1H, m), 3.70 , m), 4.08 (1H, dd), 11.2 (1H, br s), 11.9 (1H, br s)

MS ( m / e ): 318

Example  A2: Isosorbide- Of di (2-methylpropionic acid)  Produce

Except that 100 g of isosorbide-dimethonitrile in Production Example 2 was used instead of 100 g of isosorbide-dichlorononitrile in Production Example 1, the same procedure as in Example A1 was repeated to obtain the compound represented by Formula 1-2 Of isosorbide-di (2-methylpropionic acid). The yield was 93%.

[Formula 1-2]

^{1 H NMR (δ ppm; DMSO-} d 6): 1.24 (3H, d), 1.29 (3H, d), 2.73 (1H, dd), 2.79 (1H, dd), 3.45 (1H, dd), 3.51- (2H, m), 4.0 (1H, dd), 11.7 (1H, br s), 3.60 12.0 (1H, broad singlet)

MS ( m / e ): 318

Example  A3: Isosorbide- Of di (3-phenylpropionic acid)  Produce

Except that 100 g of the isosorbide-dicinonitrile of Preparation Example 3 was used instead of 100 g of the isosorbide-dichlorononitrile of Preparation Example 1, Sorbide-di (3-phenylpropionic acid). The yield was 96%.

[Formula 1-3]

^{1 H NMR (δ ppm; DMSO-} d 6): 2.52 (1H, dd), 2.59 (1H, dd), 2.79 (1H, dd), 2.84 (1H, dd), 3.48 (1H, m), 3.56 ( (1H, m), 3.71 (1H, dd), 3.75 (1H, dd), 3.95 (10H, m), 11.9 (1H, br s), 12.1 (1H, br s)

MS ( m / e ): 442

< ISB - Diester  Preparation of compound (step (2)) &gt;

Example  B1: isosorbide- Di [methyl (3-methylpropionic acid)]  Produce

100 g of the isosorbide-dichlorononitrile of Preparation Example 1 was diluted with 1 L of methanol contained in the glass reactor, and then 20 g of sulfuric acid was slowly added dropwise. The reaction mixture was refluxed for 5 hours and then cooled to room temperature. 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, and then concentrated under reduced pressure to obtain isosorbide-di [methyl (3-methylpropionic acid)]. The yield was 86%.

[Formula 1-4]

^{1 H NMR (δ ppm; DMSO-} d 6): 1.21 (3H, d), 1.24 (3H, d), 2.19 (1H, dd), 2.24 (1H, dd), 2.51 (1H, dd), 2.55 ( (1H, dd), 3.50 (2H, m), 3.64 (3H, s), 3.67 (3H, s), 3.75 , &lt; / RTI &gt; dd), 4.04 (1H, dd)

MS ( m / e ): 346

Example  B2: isosorbide- Di [isopropyl (2-methylpropionic acid)]  Produce

Except that 100 g of isosorbide-dimethacrylonitrile of Preparation Example 2 was used instead of 100 g of isosorbide-dichlorononitrile of Preparation Example 1 and 1 liter of 2-propanol was used instead of 1 L of methanol as a reaction solvent. Diisopropyl (2-methylpropionic acid)] of the following formula 1-5 was obtained by carrying out the same procedure as in Example B1. The yield was 89%.

[Formula 1-5]

^{1 H NMR (δ ppm; DMSO-} d 6):: 1.21 (3H, d), 1.24 (3H, d), 2.19 (1H, dd), 2.24 (1H, dd), 2.51 (1H, dd), 2.55 (1H, dd), 3.50 (2H, m), 3.64 (3H, s), 3.67 (3H, s), 3.75 1H, dd), 4.04 (1H, dd)

MS ( m / e ): 402

Example  B3: isosorbide- Di [benzyl (3-phenylpropionic acid)]  Produce

100 g of isosorbide-dicyanomonitrile of Preparation Example 3 was used instead of 100 g of isosorbide-dichlorononitrile of Preparation Example 1, and 500 ml of tetrahydrofuran and 100 ml of benzyl alcohol were used instead of 1 l of methanol as a reaction solvent Diisobutyl-di [benzyl (3-phenylpropionic acid)] of the following formula 1-6 was obtained by carrying out the same processes as in the case of Example B1. The yield was 91%.

[Chemical Formula 1-6]

^{1 H NMR (δ ppm; DMSO-} d 6): 2.60 (1H, dd), 2.65 (1H, dd), 2.85 (1H, dd), 2.89 (1H, dd), 3.58 (1H, m), 3.63 ( (1H, m), 3.77 (1H, dd), 3.82 (1H, dd), 3.94 (1H, d), 4.00 t), 4.86 (1H, t), 5.31 (2H, s), 5.35 (2H, s), 7.27-7.56

MS ( m / e ): 622

Example  B4: Isosorbide- Di [phenyl (3-methylpropionic acid)]  Produce

The procedure of Example B1 was repeated except that 500 mL of tetrahydrofuran and 100 mL of phenol were used instead of 1 L of methanol as a reaction solvent and the reflux stirring time was changed from 5 hours to 24 hours, Diisobutyl-di [phenyl (3-methylpropionic acid)]. The yield was 75%.

[Chemical Formula 1-7]

^{1 H NMR (δ ppm; DMSO-} d 6): 1.20 (3H, d), 1.27 (3H, d), 2.48 (4H, m), 3.52 (1H, m), 3.56 (1H, m), 3.70- 3.99 (8H, m), 7.07-7.47 (10H, m)

MS ( m / e ): 470

Example  B5: Isosorbide- Di [cyclohexyl (3-methylpropionic acid)]  Produce

The procedure of Example B1 was repeated except that 500 mL of tetrahydrofuran and 100 mL of cyclohexanol were used instead of 1 L of methanol as a reaction solvent and the reflux stirring time was changed from 5 hours to 12 hours, 1- isosorbide-di [cyclohexyl (3-methylpropionic acid)]. The yield was 88%.

[Chemical Formula 1-8]

^{1 H NMR (δ ppm; DMSO-} d 6): 1.18 (3H, d), 1.24 (3H, d), 1.34-1.75 (20H, m), 2.32 (4H, m), 3.52 (1H, m), 3.56 (1H, m), 3.77-4.02 (10H, m)

MS ( m / e ): 482

&Lt; Antibacterial activity of compounds of formulas 1-1 to 1-8 and Antifungal activity  Test>

[Production Example C1]

Strain culture (activation)

Prior to testing for antimicrobial activity and antifungal activity, several cultures were performed to increase the activity of the bacteria.

Bacteria were streaked on a Nutrient Agar (NA) plate having the components and contents shown in Table 1, incubated in a 37 ° C. incubator until a colony was confirmed, and after confirming whether or not the colonies were contaminated, Was further cultured under the same conditions to increase the activity of the bacteria.

The fungi were similarly streaked on a Potato Dextrose Agar (PDA) plate having the components and contents as shown in Table 2, and cultured until incubation was confirmed in a 30 ° C incubator. After confirming contamination, randomly selected colonies were again subjected to the same conditions To increase the activity of the bacteria.

No allowance  Branching with alcohol nucleus Dicarboxyl  Preparation of compound-containing culture medium

The liquid medium was prepared by adding the compounds of Formulas 1-1 to 1-8 to each liquid medium in an amount of 0.5 wt%, 0.7 wt%, 1 wt%, 1.2 wt%, 1.5 wt%, and 2 wt% %.

In the case of bacteria, Tryptic Soy Broth (TSB) having the components and contents shown in Table 3 below was used as a liquid medium, and Potato Dextrose Broth (PDB) having the components and contents of the following Table 4 was used as a liquid medium for fungi. The liquid medium containing the branched dicarboxylic compound having an alcohol-free alcohol core was prepared by dispensing in a 14 ml test tube.

inoculation Fungus  Ready

Each colony activated by culturing on an agar plate was used as an inoculum for inoculation into a culture solution containing the compound of Formulas 1-1 to 1-8 after confirming morphological characteristics and further confirming external contamination. Each strain was plated with platinum on a colony and diluted in 9 ml of physiological saline. The dilution concentration was adjusted to a value of McFarland standard 0.5. When adjusted to a McFarland standard of 0.5, the concentration of cells in saline was 1.5 x 10 ⁸ CFU / ml.

Inoculation and culture

30 μl of the respective concentrations of the bacterial solutions were added to 3 ml of each medium containing the compounds of Formulas 1-1 to 1-8 for each concentration, and the bacterial solution was diluted to 1/100 and then 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 inoculum growth (preliminary test)

Stirring was carried out on an agar plate in order to easily confirm the growth of the cells in the inoculated culture solution. Some of the bacterial cultures incubated for 24 hours and plated for 72 hours were plated on Tryptic Soy Agar (TSA) plates and Potato Dextrose Agar (PDA) plates at 37 ° C and 30 ° C Were cultured until the growth of the bacteria was confirmed. Specifically, the growth of the bacteria was confirmed by culturing the bacteria for 24 hours. When the bacteria were cultured for 72 hours, the growth of the bacteria was confirmed. After streaking and culturing, the presence or absence of growth was easily confirmed, and the concentrations of the compounds of Formulas 1-1 to 1-8 were able to be reset.

Minimum growth inhibition concentration ( MIC ) Judgment

Experiments were conducted to set the minimum growth inhibition concentration (MIC) based on the concentration set by the preliminary test. Fungal solutions were inoculated in a liquid medium containing the compounds of the formulas 1-1 to 1-8 at the set concentrations. The liquid medium containing the compounds of Formulas 1-1 to 1-8 was placed in a 14 ml test tube in an amount of 3 ml, and the inoculum was prepared and used in the same manner as in the preparation of the inoculum solution described above (1.5 for physiological saline) x 10 &lt; ⁸ &gt; CFU / ml). 30 μl of the bacterial solution in the liquid medium After inoculation, the bacteria were incubated at 37 ° C for 24 hours, and the fungi were cultured at 30 ° C for 72 hours. After incubation, the culture broth was plated on an agar plate to confirm the growth of the bacteria. Specifically, bacteria were plated on Nutrient Agar (NA) plate and fungi were plated on Potato Dextrose Agar (PDA) plate. After culturing by plating, the concentration at which no colonies were formed was set as the minimum growth inhibitory concentration (MIC).

[Example C1] Preliminary test for three kinds of bacteria and two kinds of fungi

Three species of bacteria, Pseudomonas aeruginosa KCTC 2513, Staphylococcus aureussubsp. aureus KCTC 3881 and Escherichia coli were used. After activation, the mycorrhizal broth was prepared according to McFarland standard 0.5. The bacterial solution was inoculated on Tryptic Soy Broth to which the compound of Formulas 1-1 to 1-8 was added and cultured for 24 hours at 30 ° C at 200 rpm. After incubation for 24 hours, the culture broth was streaked on a Nutrient Agar (NA) plate, and the presence or absence of growth by concentration (the concentration was the% by weight of the compound of Formulas 1-1 to 1-8 based on 100% Respectively.

Candida albicans and Aspergillus niger were used as the two fungi. After activation, the strains were prepared according to McFarland standard 0.5. The mycelial liquid was inoculated on Potato Dextrose Broth to which the compound of Formulas 1-1 to 1-8 was added, and cultured at 200 rpm at 30 ° C for 72 hours. After culturing for 72 hours, the culture was streaked on a Potato Dextrose Agar plate, and the presence or absence of growth by concentration (the concentration was the weight% of the compound of Formulas 1-1 to 1-8 based on the total culture weight of 100% by weight) Respectively.

As a result, as shown in Tables 5 to 12 below, the compounds of Formulas 1-1 to 1-8 were found to have antimicrobial activity against three bacteria regardless of their high concentration and low concentration throughout the various substituent structures, Of the antimicrobial activity.

[Example C2] MIC test of three bacteria and two fungi

Based on the preliminary test results of Example C1, the concentration range of the compounds of Formulas 1-1 to 1-8 was set and the MIC test was conducted. Experiments were conducted after setting the concentration range of the compound of Formulas 1-1 to 1-8 to 5,000 to 20,000 ppm (MIC test was conducted in ppm on the basis of the concentration (% by weight) of the preliminary test). MIC test results showed excellent antibacterial activity in the presence of at least 5,000 ppm of compounds of formulas 1-1 to 1-8, depending on the strains and the compounds of Formulas 1-1 to 1-8, 5,000 ppm or more in the presence of the compound of Formulas 1-1 to 1-8.

Claims (23)

A compound represented by the following formula (A):
(A)
XYOMOYX
In the above formula (A)
X is -COOR _3, where R ₃ is independently, hydrogen, alkyl, aryl, arylalkyl or cycloalkyl each,
Y is -CR ₁ HCR ₂ H-, wherein R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, Aryl or cycloalkyl,
M is a divalent organic group derived from anhydrous alcohol. The compound according to claim 1, wherein M is a divalent organic group derived from isosorbide, isomannide or isoidide. 2. A compound according to claim 1, wherein M is selected from the group consisting of:

The compound according to claim 1, which is represented by the following formula (1):
[Chemical Formula 1]

In Formula 1,
R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, aryl, heteroaryl or cycloalkyl,
R &lt; ₃ &gt; are each independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl. The compound according to claim 1, which is represented by the following formula (2):
(2)

In Formula 2,
R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, aryl, heteroaryl or cycloalkyl,
R &lt; ₃ &gt; are each independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl. The compound according to claim 1, which is represented by the following formula (3):
(3)

In Formula 3,
R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, aryl, heteroaryl or cycloalkyl,
R &lt; ₃ &gt; are each independently hydrogen, alkyl, aryl, arylalkyl or cycloalkyl. (1) carrying out a Michael reaction of an alcohol without anhydride and a nitrile compound; And
(2) adding sodium hydroxide or alcohol to the compound obtained from the Michael reaction.
A process for producing a compound represented by the formula (A)
(A)
XYOMOYX
In the above formula (A)
X is -COOR _3, where R ₃ is independently, hydrogen, alkyl, aryl, arylalkyl or cycloalkyl each,
Y is -CR ₁ HCR ₂ H-, wherein R ₁ and R ₂ are each independently hydrogen, alkyl, aryl, heteroaryl or cycloalkyl, provided that at least one of R ₁ and R ₂ is alkyl, Aryl or cycloalkyl,
M is a divalent organic group derived from anhydrous alcohol. 8. The method according to claim 7, wherein M is a divalent organic group derived from isosorbide, isomannide or isoidide. The method according to claim 7, wherein M is selected from the following formula:

The process according to claim 7 wherein the nitrile compound of step (1) is selected from the group consisting of crotononitrile, methacrylonitrile, cinnamonitrile, 3- (furan-2-yl) prop- &Lt; / RTI &gt; or a pharmaceutically acceptable salt thereof. The process for producing a compound represented by the formula (A) according to claim 7, wherein the nitrile compound is reacted in an amount of 1.5 to 3 molar equivalents relative to 1 molar equivalent of an alcohol free of alcohol in step (1). 8. The process according to claim 7, wherein the alcohol of step (2) is selected from methanol, 2-propanol, benzyl alcohol, phenol, cyclohexanol or mixtures thereof. 8. The process according to claim 7, wherein 50 to 150 g of sodium hydroxide or 0.05 to 2 l of alcohol are added to 100 g of the compound obtained from the Michael reaction of step (2). An antimicrobial composition comprising a compound represented by the formula (A) according to any one of claims 1 to 6. The antimicrobial composition according to claim 14, wherein the content of the compound represented by the formula (A) is 0.005 to 30% by weight, based on 100% by weight of the antimicrobial composition. 15. The method according to claim 14, wherein the at least one compound selected from the group consisting of phenoxyethanol, alkanediol, methylchloroisothiazolinone, methylisothiazolinone, benzoic acid or its salt, benzoic acid ester derivative, salicylic acid or its salt, 4-hydroxybenzoic acid or its salt, Or a salt thereof, or a salt thereof, or a salt thereof, a salt thereof, or a salt thereof, a salt thereof, a salt thereof, a salt thereof or a salt thereof, a dehydroacetic acid or its salt, a dehydroacetic acid ester derivative, a benzyl alcohol, a 2-methylisothiazol- &Lt; / RTI &gt; wherein the antimicrobial composition further comprises one or more additives. An antifungal composition comprising a compound of formula (A) according to any one of claims 1 to 6. The antifungal composition according to claim 17, wherein the content of the compound represented by the formula (A) is 0.005 to 30% by weight, based on 100% by weight of the antifungal composition. 18. The method of claim 17, wherein the at least one compound selected from the group consisting of phenoxyethanol, alkanediol, methylchloroisothiazolinone, methylisothiazolinone, benzoic acid or a salt thereof, benzoic acid ester derivative, salicylic acid or a salt thereof, 4-hydroxybenzoic acid or a salt thereof, Or a salt thereof, or a salt thereof, or a salt thereof, a salt thereof, or a salt thereof, a salt thereof, a salt thereof, a salt thereof or a salt thereof, a dehydroacetic acid or its salt, a dehydroacetic acid ester derivative, a benzyl alcohol, a 2-methylisothiazol- &Lt; / RTI &gt; further comprising at least one additive selected from the group consisting &lt; RTI ID = 0.0 &gt; of: &lt; / RTI & 14. An agent comprising the antimicrobial composition according to claim 14. 21. The formulation according to claim 20, wherein the preparation is selected from the group consisting of a cosmetic, a skin-care agent, a detergent, a colorant, a coating or a plant protection agent. 18. An agent comprising an antifungal composition according to claim 17. 23. The preparation according to claim 22, wherein the preparation is selected from the group consisting of a cosmetic, a skin-care agent, a detergent, a colorant, a coating or a plant protection agent.