KR20130130350A - Novel method for preparing isosorbide derivative - Google Patents

Abstract

Disclosed is a method for preparing a novel isosorbide derivate. The present invention provides a method for preparing isosorbide by making isosorbide react with a hydroxybenzoic acid derivative under the presence of an aprotic polar solvent and a sulfonic acid catalyst. The method can minimize the generation of byproducts to improve purity, and significantly increase the yield of the isosorbide derivate even when a simple process by precipitation without separation through chromatography. [Reference numerals] (AA) START;(BB) Mix isosorbide, a hydroxybenzoic acid derivative, a sulfonic acid catalyst, and an aprotic polar solvent, followed by reaction;(CC) Step a;(DD) Precipitate formed;(EE) Step b;(FF) Precipitate filtering;(GG) Step c;(HH) END

Description

TECHNICAL FIELD [0001] The present invention relates to a novel isosorbide derivative,

The present invention relates to a process for producing an isosorbide derivative. More particularly, the present invention relates to a process for producing an isosorbide derivative which can obtain a reaction product by precipitation using an aprotic polar solvent and a weak acid catalyst, ≪ / RTI >

With the increase in global energy demand and the depletion of traditional energy sources, alternative energy development is now being watched. Among these, biomass is a renewable quantitative biomass that has attracted much attention as seen in "Fuel production at Biomes", an alternative energy development project conducted by the US Department of Energy. Among them, isosorbide is one of the biomass-derived substances that can replace the petrochemical-based basic compounds that have already been produced and used by using sorbitol, which can obtain herbaceous biomass through various processes. Much research has been going on.

 Isosorbide is a substance that can be obtained through a simple dehydration process of sorbitol and is attracting attention as a monomer required for synthesis of a next generation high performance, environmentally friendly material which can replace the existing polymer products.

Isosorbide is a heterocyclic compound derived from glucose, which can be obtained by hydrogenating glucose to form sorbitol, which can be double dehydrated. The isosorbide has a V-shaped structure in which two tetrahydrofuran rings are bonded at an angle of 120 ° and has a hydroxyl group at carbon positions 2 and 6.

Isosorbide is a compound of a solid structure having optical asymmetry, and derivatives thereof are useful as raw materials for pharmaceutical raw materials and high-functional industrial materials in that they exhibit specific functions. In addition, isosorbide is excellent in optical properties and thermal properties and is being used in optical electronic components such as optical disk substrates, optical fibers, and lenses.

In addition, bisphenol A-based polymers, such as polycarbonate, which have been widely used, have various environmental and environmental hormone problems due to bisphenol A which can be eluted at the time of use.

Therefore, a manufacturing method capable of replacing bisphenol, which is a raw material of polycarbonate, and having excellent optical and thermal characteristics, as an isosorbide derivative, which is known to be free from the risk of elution of environmental hormones and the like, .

DISCLOSURE OF THE INVENTION An object of the present invention is to solve the above problems and to provide a process for producing an isosorbide derivative by using a catalyst which is a sulfonic acid or a sulfonic acid derivative and an aprotic polar solvent to minimize the generation of byproducts, It is another object of the present invention to provide a process for producing an isosorbide derivative which can separate a product using a simple process without using separation by use and improve the process yield.

In order to achieve the above object, according to one aspect of the present invention, there is provided a process for preparing a compound represented by the following formula (1) and a compound represented by the following formula (2) in an aprotic polar aprotic solvent, To give a compound represented by the following general formula (4).

[Formula 1]

(2)

In Formula 2, R ¹ is a hydrogen atom, a deuterium atom, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C6 to C30 aryl group, or a substituted or unsubstituted C2 to C30 heteroaryl group, and R ² is hydrogen, deuterium, or a C1 to C30 alkyl group.

(3)

In Formula 3, R ³ is a C1 to C30 alkyl group, a C6 to C30 aryl group, a C7 to C30 alkylaryl group, or a C7 to C30 arylalkyl group.

[Chemical Formula 4]

In Formula 4, each R ¹ is independently a hydrogen atom, a deuterium atom, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C6 to C30 aryl group, or a substituted or unsubstituted C2 to C30 heteroaryl group And R ² is each independently hydrogen, deuterium or a C1 to C30 alkyl group.

In the present invention, the isosorbide derivative can be obtained by a precipitation method without separation by chromatography.

In the present invention, the aprotic polar solvent may have a dipole moment value of 2.5 to 8.0 D, preferably 3.5 to 6.0 D.

In the present invention, the aprotic polar solvent may be at least one selected from the group consisting of sulfolane, dimethylformamide, dimethyl sulfoxide, and hexamethylphosphoric triamide. have.

In the present invention, the catalyst may have a Pka value of -2.8 to 2.0.

In the present invention, the catalyst may be at least one selected from the group consisting of para-toluenesulfonic acid, 4-ethylphenylsulfonic acid and phenylmethylsulfonic acid.

In the present invention, the compound represented by Formula 2 is preferably selected from the group consisting of 4-hydroxybenzoic acid, 4-methoxybenzoic acid and 4-hydroxy-3-methylbenzoic acid (4- hydroxy-3-methylbenzoic acid).

In the present invention, the compound represented by the general formula (4) is selected from the group consisting of isosorbide 2,5-bis (4-hydroxybenzoate), isosorbide 2,5-bis Isosorbide 2,5-bis (4-hydroxy-3-methylbenzoate) and isosorbide 2,5-bis (4-methoxybenzoate) -bis (4-methoxybenzoate)).

According to the present invention, there is provided a process for preparing an isosorbide derivative,

(a) mixing and reacting a compound represented by Formula 1, a compound represented by Formula 2, an aprotic polar solvent, and a catalyst represented by Formula 3;

(b) forming a precipitate from the reaction product of step (a); And

(c) filtering the precipitate to obtain a compound represented by the general formula (4).

In the present invention, the step (a) may be carried out by stirring at 120 to 160 ° C for 3 to 5 hours.

In the step (b) of the present invention, the reaction product of the step (a) may be added with an alcohol and water to form a precipitate.

In the present invention, the alcohol may be at least one selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol.

The method for preparing the isosorbide derivative according to the present invention may further comprise the step of drying the precipitate after the step (b) and removing the aprotic polar solvent from the precipitate.

In the present invention, removal of the aprotic polar solvent may be performed by at least one selected from the group consisting of methylene chloride and chloroform.

In the present invention, the drying step after step (c) may be further performed.

In the present invention, the compound represented by Formula 4 may be a monomer used for polycarbonate polymerization.

According to the present invention, the production of isosorbide derivatives using a sulfonic acid or sulfonic acid derivative catalyst and an aprotic polar solvent enables to minimize the production of byproducts to increase the purity of the product, The process yield can be remarkably increased by using a simple process according to the precipitation method.

According to the present invention, it is possible to provide a process for producing an isosorbide derivative which can replace bisphenol A, which is a petroleum-based material conventionally used for polycarbonate polymerization, and which can compensate for the disadvantage of isosorbide, Method can be provided.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a flowchart sequentially showing a method for producing an isosorbide derivative of the present invention. FIG.
Fig. 2 shows the product separation by TLC in Comparative Example 1. Fig.
3 shows the results of nuclear magnetic resonance analysis of the isosorbide derivative prepared according to Example 1 of the present invention.
Fig. 4 shows the results of nuclear magnetic resonance analysis of the isosorbide derivative prepared according to Comparative Example 1. Fig.
5 is a comparison of the results of thermogravimetric analysis of the isosorbide derivative, isosorbide and bisphenol A prepared according to Example 1 of the present invention.

The invention is capable of various modifications and may have various embodiments, and particular embodiments are exemplified and will be described in detail in the detailed description. It is to be understood, however, that the invention is not to be limited to the specific embodiments, but includes all modifications, equivalents, and alternatives falling within the spirit and scope of the invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, the present invention will be described in detail with reference to the accompanying drawings.

As used herein, unless otherwise defined, the term "substituted" means that at least one hydrogen in the substituent or compound is replaced by a substituent selected from the group consisting of deuterium, a halogen group, a hydroxy group, an amino group, a C1 to C20 amine group, a nitro group, a C1 to C30 silyl group, Means an alkyl group, a C1 to C10 alkylsilyl group, a C3 to C30 cycloalkyl group, a C6 to C30 aryl group, a C2 to C30 heteroaryl group, a C1 to C20 alkoxy group, a C1 to C10 trifluoroalkyl group or a cyano group .

Means one to three heteroatoms selected from the group consisting of N, O, S and P in one functional group, and the remainder is carbon, unless otherwise defined.

In the present specification, the term "combination thereof" means that two or more substituents are bonded to each other via a linking group or two or more substituents are condensed and bonded.

As used herein, unless otherwise defined, an "alkyl group" means an aliphatic hydrocarbon group. The alkyl group may be a "saturated alkyl group" that does not contain any double or triple bonds.

The alkyl group may be an "unsaturated alkyl group" comprising at least one double bond or triple bond. The alkyl group, whether saturated or unsaturated, can be branched, straight chain or cyclic.

The alkyl group may be a C1 to C30 alkyl group. More specifically, the alkyl group may be a C1 to C10 alkyl group, a C1 to C6 alkyl group, or a C1 to C3 alkyl group.

For example, the C1 to C4 alkyl groups may have 1 to 4 carbon atoms in the alkyl chain, i.e., the alkyl chain may be optionally substituted with one or more substituents selected from the group consisting of methyl, ethyl, propyl, iso-propyl, n-butyl, Indicating that they are selected from the group.

Specific examples of the alkyl group include a methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, t-butyl group, pentyl group, hexyl group, ethenyl group, Butyl group, cyclopentyl group, cyclohexyl group, and the like.

An "aryl group" includes a monocyclic or fused ring polycyclic (i. E., A ring that divides adjacent pairs of carbon atoms) functional groups.

 "Heteroaryl group" means that the aryl group contains 1 to 3 heteroatoms selected from the group consisting of N, O, S and P, and the remainder is carbon. When the heteroaryl group is a fused ring, it may contain 1 to 3 heteroatoms in each ring.

When used in combination, such as "alkylaryl" or "arylalkyl ", the terms alkyl and aryl of each of the above have the meanings and contents indicated above.

The term "arylalkyl" refers to aryl-substituted alkyl radicals such as benzyl.

The term "alkylaryl" means an alkyl substituted aryl radical.

Hereinafter, a method for producing the isosorbide derivative of the present invention will be described.

The process for producing an isosorbide derivative of the present invention is characterized in that an isosorbide and a hydroxybenzoic acid derivative compound are reacted with a polar aprotic solvent in the presence of a catalyst which is a sulphonic acid or a sulfonic acid derivative, To form a Void derivative. The preparation method does not require separation by chromatographic use and is characterized in that the product is separated according to the precipitation method.

Specifically, the isosorbide derivative is represented by the following formula (1).

[Formula 1]

In addition, the hydroxybenzoic acid derivative compound means a compound represented by the following formula (2).

For example, 4-hydroxybenzoic acid, 4-methoxybenzoic acid or 4-hydroxy-3-methylbenzoic acid, , And 4-hydroxybenzoic acid can be preferably applied

(2)

In Formula 2, R ¹ is a hydrogen atom, a deuterium atom, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C6 to C30 aryl group, or a substituted or unsubstituted C2 to C30 heteroaryl group, and R ² is hydrogen, deuterium, or a C1 to C30 alkyl group.

In addition, the aprotic polar solvent preferably has a dipole moment value in the range of 2.5 to 8.0 D, preferably 3.5 to 6.0 D.

For example, an aprotic polar solvent such as sulfolane, dimethylformamide, dimethyl sulfoxide or hexamethylphosphoric triamide may be used, and preferably, , Sulfolane solvents can be used.

The catalyst, which is a sulphonic acid or a sulfonic acid derivative, is represented by the following formula (3).

(3)

In Formula 3, R ³ is a C1 to C30 alkyl group, a C6 to C30 aryl group, a C7 to C30 alkylaryl group, or a C7 to C30 arylalkyl group.

The catalyst preferably has a Pka value of -2.8 to 2.0, and may be prepared by reacting para-toluenesulfonic acid, 4-ethylphenylsulfonic acid, phenylmethylsulfonic acid, Can be applied.

The product produced by the above reaction may be a compound represented by the following general formula (4).

[Chemical Formula 4]

In the general formula (4), R1 is independently a hydrogen atom, a deuterium atom, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C6 to C30 aryl group, or a substituted or unsubstituted C2 to C30 heteroaryl group , And R 2 are each independently hydrogen, deuterium, or a C 1 to C 30 alkyl group.

The isosorbide derivative represented by the above-mentioned general formula (4) is preferably selected from the group consisting of isosorbide 2,5-bis (4-hydroxybenzoate), isosorbide 2,5-bis (4-hydroxy-3-methylbenzoate) and isosorbide 2,5-bis (4-methoxybenzoate) (isosorbide 2, 5-bis (4-methoxybenzoate)), and these compounds can be used as monomers in the polycarbonate polymerization.

BRIEF DESCRIPTION OF THE DRAWINGS FIG. 1 is a flowchart sequentially showing a method for producing an isosorbide derivative of the present invention. FIG.

Referring to FIG. 1, the method for producing the isosorbide derivative of the present invention can be divided into three steps.

Step (a): Nonpolarity  Reaction with polar solvent, catalyst

First, the compound represented by Formula 1, the compound represented by Formula 2, the aprotic polar solvent, and the catalyst represented by Formula 3 are mixed and reacted (Step a).

The description related to the compounds represented by the formulas (1) and (2), the solvent and the catalysts described above are the same as those described above, and therefore will not be described.

The reaction can be carried out by stirring at 120 to 160 ° C for 3 to 5 hours.

Step (b): Formation of a precipitate from the reaction product

Thereafter, a precipitate is formed from the reaction product of step (a) (step b).

The precipitate is formed according to a precipitation method in which an alcohol and water are added. The alcohol may be methanol, ethanol, n-propanol, isopropanol, n-butanol or tert-butanol.

When the precipitate is formed, it may be further dried to remove the aprotic polar solvent from the precipitate. The removal of the aprotic polar solvent may be performed in methylene chloride, chloroform, or the like.

Step (c): The precipitate By filtering Isosobaid  Obtain a derivative

Finally, the precipitate is filtered to obtain the isosorbide derivative of Formula 4 (Step c).

The filtered isosorbide compound may be further subjected to a drying process to obtain a solid form of the product.

Hereinafter, preferred embodiments of the present invention will be described in detail.

[Example]

Example  One

25 ml of an aprotic organic solvent sulfolane was added to a round flask, and 5 g (34.2 mmol) of isosorbide, 31.2 g (136.9 mmol) of 4-hydroxybenzoic acid, 650 mg (3.42 mmol) of para-toluenesulfonic acid was added and stirred uniformly in an oil bath at 140 ° C for 4 hours to obtain a product.

After completion of the reaction, the product of the reaction was dissolved with ethanol (150 ml), and the solution was added to 500 ml of water. After 12 hours, the resulting precipitate was filtered and dried, followed by stirring in 200 ml of methylene chloride for 3 hours. The filtered product was dried sufficiently to give isosorbide 2,5-bis (4-hydroxybenzoate) as a white solid in yield of 53 %.

The resulting white solid was confirmed to be isosorbide 2,5-bis (4-hydroxybenzoate) by nuclear magnetic resonance analysis, and the analysis result is shown in FIG.

The analysis data are as described below.

1H NMR (400 MHz, DMSO) 10.41 (s, 2H), 7.80 (m, 4H), 6.87 (m, 4H), 5.33 4.58 (d, 1 H), 3.91 - 3.98 (m, 4 H)

Comparative Example  One

(1.368 mmol, 50%) as a catalyst, 20 g (225 mmol) of toluene as a solvent, and 20 g (225 mmol) of diethylene glycol dimethyl ether ) Was reacted at 110 < 0 > C with the use of 832 mg (5.13 mmol) of iodomethane.

The product produced by the reaction was separated by chromatography using TLC (thin layer chromatography) using a solvent mixture of hexane (Hexane) and ethyl acetate (ethyl acetate) in a ratio of 2: 3.

The separation of the product by using chromatography according to Comparative Example 1 is shown in Fig. Here, what is visible in the middle square is the product. It was found that the separation of the target material and the side products in the product of the reaction was not easy.

When the reaction was terminated by TLC (Thin-Layer Chromatography) after the reaction was terminated, a large amount of side-product was produced and it was impossible to separate by a simple separation method, recrystallization. In addition, when the test tube of the cleanest spot was separated from the thin film chromatography and dried and analyzed by NMR, it was confirmed that the separation was not performed as shown in FIG.

Nuclear magnetic  Resonance analysis ^One H- NMR )

Nuclear magnetic resonance analysis was performed on the isosorbide derivatives prepared according to Example 1 and Comparative Example 1. Nuclear magnetic resonance analysis was performed on Bruker's AVIII 400 ( ¹ H-400 MHz) after each product was dissolved in deuterated dimethyl sulfoxide (DMSO) containing 0.05% of internal standard tetramethylsilane (TMS).

The results of nuclear magnetic resonance analysis for Example 1 are shown in FIG. 3, and the results of nuclear magnetic resonance analysis for Comparative Example 1 are shown in FIG.

4, it can be seen that the product according to Comparative Example 1 has a somewhat neat graph as compared with that of Example 1 of the nuclear magnetic resonance analysis. In other words, it was found that the side-product of the isolated isosorbide derivative obtained by using the chromatography of Comparative Example 1 was relatively larger than that of Example 1.

According to the above results, it can be seen that, according to the method for preparing an isosorbide derivative using the precipitation method of the present invention, the isosorbide derivative having a high purity can be obtained by minimizing by-products by a simple process as compared with the prior art.

Thermal weight  analysis( TGA , Thermogravimetric Analysis )

The thermogravimetric analysis of the isosorbide derivative, isosorbide and bisphenol A prepared according to Example 1 was carried out, and the results are shown in Fig.

According to Fig. 5, the isosorbide derivative of Example 1 hardly showed any weight loss to about 350 DEG C, whereas the heat loss was abruptly observed at about 150 DEG C for isosorbide and about 250 DEG C for bisphenol A . Therefore, it was found that the isosorbide derivative prepared according to the present invention had excellent thermal stability.

Therefore, it can be seen that the polycarbonate having excellent heat resistance can be produced by using the isosorbide derivative according to the production method of the present invention for polycarbonate polymerization.

Claims (16)

1. A process for preparing a compound represented by the following formula (4) by reacting a compound represented by the following formula (1) and a compound represented by the following formula (2) with an aprotic polar aprotic solvent under a catalyst represented by the following formula ≪ / RTI >
[Chemical Formula 1]

(2)

In Formula 2, R ¹ is a hydrogen atom, a deuterium atom, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C6 to C30 aryl group, or a substituted or unsubstituted C2 to C30 heteroaryl group, and R ² is hydrogen, deuterium, or a C1 to C30 alkyl group.
(3)

In Formula 3, R ³ is a C1 to C30 alkyl group, a C6 to C30 aryl group, a C7 to C30 alkylaryl group, or a C7 to C30 arylalkyl group.
[Chemical Formula 4]

In Formula 4, each R ¹ is independently a hydrogen atom, a deuterium atom, a substituted or unsubstituted C1 to C30 alkyl group, a substituted or unsubstituted C6 to C30 aryl group, or a substituted or unsubstituted C2 to C30 heteroaryl group And R ² is each independently hydrogen, deuterium or a C1 to C30 alkyl group.
The method of claim 1,
Characterized in that the isosorbide derivative is obtained by the precipitation method without separation by chromatographic method.
The method of claim 1,
Wherein the aprotic polar solvent has a dipole moment value of 2.5 to 8.0 D. < RTI ID = 0.0 > 11. < / RTI >
The method of claim 1,
The aprotic polar solvent is at least one member selected from the group consisting of sulfolane, dimethylformamide, dimethyl sulfoxide, and hexamethylphosphoric triamide. Method for preparing isosorbide derivatives.
The method of claim 1,
Wherein the catalyst has a Pka value of -2.8 to 2.0.
The method of claim 1,
Wherein the catalyst is at least one selected from the group consisting of para-toluenesulfonic acid, 4-ethylphenylsulfonic acid, and phenylmethylsulfonic acid. ≪ / RTI >
The method of claim 1,
Compound represented by the formula (2) is 4-hydroxybenzoic acid (4-hydroxybenzoic acid), 4-methoxybenzoic acid (4-methoxybenzoic acid) and 4-hydroxy-3-methylbenzoic acid (4-hydroxy-3 -methylbenzoic acid) method for producing an isosorbide derivative, characterized in that at least one member selected from the group consisting of.
The method of claim 1,
Compound represented by the formula (4) is isosorbide 2,5-bis (4-hydroxybenzoate) (isosorbide 2,5-bis (4-hydroxybenzoate)), isosorbide 2,5-bis (4-hydroxy Isosorbide 2,5-bis (4-hydroxy-3-methylbenzoate) and isosorbide 2,5-bis (4-methoxybenzoate) 4-methoxybenzoate)) method for producing an isosorbide derivative, characterized in that one selected from the group consisting of.
The method of claim 1,
The method for producing the isosorbide derivative comprises:
(a) mixing and reacting a compound represented by Formula 1, a compound represented by Formula 2, an aprotic polar solvent, and a catalyst represented by Formula 3;
(b) forming a precipitate from the reaction product of step (a); And
(c) filtering the precipitate to obtain a compound represented by the general formula (4).
10. The method of claim 9,
The step (a)
Followed by stirring at 120 to 160 DEG C for 3 to 5 hours.
10. The method of claim 9,
Wherein the step (b) comprises forming a precipitate by adding an alcohol and water to the reaction product of the step (a).
12. The method of claim 11,
Wherein the alcohol is at least one selected from the group consisting of methanol, ethanol, n-propanol, isopropanol, n-butanol and tert-butanol.
10. The method of claim 9,
The method for producing an isosorbide derivative according to the present invention may further comprise the step of drying the precipitate after the step (b) and further removing the aprotic polar solvent from the precipitate .
The method of claim 13,
Wherein the removal of the aprotic polar solvent is carried out by at least one selected from the group consisting of methylene chloride and chloroform.
10. The method of claim 9,
Wherein the step (c) is followed by a step of drying the isosorbide derivative.
The method of claim 1,
Wherein the compound represented by Formula 4 is a monomer used for polycarbonate polymerization.

Images