KR102464958B1 - Method of preparing 5-acyloxymethyl-2-furfural from glucose - Google Patents

Abstract

A method for producing 5-acyloxymethyl-2-furfural from glucose is disclosed. The manufacturing method is (1) preparing a mixture containing glucose (D-Glucose) and D-fructose (D-Fructose) by isomerization reaction (isomerization reaction) of glucose (D-Glucose) in the presence of an isomerase step; (2) D-glucopyranose and D-fructofuranose in which glucose and D-fructose in the mixture of step (1) are cycled, respectively, are immobilized enzyme ) by trans-esterification reaction with an acyl donor in the presence of 6-monoacyl-glucopyranose (MAG) and 1,6-diacyl-fructofuranose Preparing a mixture containing (1,6-Diacyl-fructofuranose, DAF); (3) Isomerization of the mixture of step (2) in the presence of isomerase to obtain 6-monoacyl-glucopyranose (MAG) and 6-monoacyl-fructofuranose (MAF) and 1,6-diacyl-fructofuranose (DAF); (4) The mixture of step (3) is trans-esterified with an acyl donor in the presence of an immobilized enzyme to obtain 6-monoacyl-glucopyranose (MAG) and 1,6-diacyl-fructofuranose (DAF). Preparing a mixture comprising; And (5) 5-acyloxymethyl-2-furfural (5-acyloxymethyl-2-furfural (5- It may include; preparing acyloxymethyl-2-furfural, AMF).
The method for producing 5-acyloxymethyl-2-furfural of the present invention has a simple reaction route, and a heterogeneous catalytic reaction using an immobilized enzyme and a cation exchange resin using an enzyme and a chemical catalyst. A hybrid reaction is used, separation and purification are easy, and the catalyst can be recycled, resulting in high economic efficiency. In addition, the production method of the present invention has mild reaction conditions that do not use high temperature / high pressure, and efficiently 5-acyloxymethyl-2-furfural (5-acyloxymethyl-2-furfural (5- acyloxymethyl-2-furfural), in particular 5-acetoxymethyl-2-furfural (AMF).

Description

Method for producing 5-acyloxymethyl-2-furfural from glucose {METHOD OF PREPARING 5-ACYLOXYMETHYL-2-FURFURAL FROM GLUCOSE}

The present invention relates to a method for producing 5-acyloxymethyl-2-furfural, and more particularly, to a method for preparing 5-acyloxymethyl-2-furfural from glucose, particularly 5-acetate. It relates to a method for producing 5-acetoxymethyl-2-furfural (AMF).

In recent years, many efforts have been made to overcome the depletion of natural resources. In particular, oil resources are limited, and the finite amount of oil on earth cannot keep up with demand. In lieu of limited resources, bio-based chemicals are considered as a potential renewable and sustainable source. In green chemistry, the production of furan derivatives from sugars is a promising energy source.

Among them, 2,5-dimethylfuran (DMF) and 5-ethoxymethylfurfural (EMF) can be used as biofuels. In particular, DMF has a high energy density similar to that of gasoline. 2,5-furan-dicarboxylic acid (FDCA) has the potential for a variety of applications. FDCA can replace monomers in polymeric materials such as terephthalic acid (TPA), which is best known as a precursor of polyester to PET.

5-Hydroxymethyl-2-furfural (HMF) has the potential to create networks of numerous furan derivatives. Furan compounds such as FDCA and DMF, which are regarded as starting materials for bioplastics and biofuels, can be produced by conducting hydrogenation and dehydration from HMF. However, due to the hydrophilic molecules in the HMF phase, it is difficult to separate the final product from the solvent through a liquid-liquid extraction method, and it is difficult to obtain a high purity product due to difficult separation and purification.

In addition, the production of industrial HMF is limited due to the characteristics of HMF and the inefficiency of the synthesis process. The HMF synthesis process using special reaction conditions such as ionic liquids, microwave heating, or supercritical solvents currently has a problem that is not suitable for commercialization.

An object of the present invention is 5-acyloxymethyl-2, which has a simple reaction route as an alternative platform compound for HMF, is easy to separate and purify due to a heterogeneous catalytic reaction using an immobilized enzyme and a cation exchange resin, and is highly economical because the catalyst can be recycled. - To provide a method for producing furfural (5-acyloxymethyl-2-furfural), particularly 5-acetoxymethyl-2-furfural (5-acetoxymethyl-2-furfural, AMF).

In addition, an object of the present invention is to have mild reaction conditions without using high temperature / high pressure, and to use 5-acyloxymethyl-2-furfural (5-acyloxymethyl-2 -furfural), in particular, to provide a method for efficiently producing 5-acetoxymethyl-2-furfural (5-acetoxymethyl-2-furfural, AMF).

According to one aspect of the present invention, (1) isomerization reaction of glucose (D-Glucose) in the presence of an isomerization enzyme to obtain glucose (D-Glucose) and D-fructose (D-Fructose). preparing a mixture; (2) D-glucopyranose and D-fructofuranose in which glucose and D-fructose in the mixture of step (1) are cycled, respectively, are immobilized enzyme ) by trans-esterification reaction with an acyl donor in the presence of 6-monoacyl-glucopyranose (MAG) and 1,6-diacyl-fructofuranose Preparing a mixture containing (1,6-Diacyl-fructofuranose, DAF); (3) Isomerization of the mixture of step (2) in the presence of isomerase to obtain 6-monoacyl-glucopyranose (MAG) and 6-monoacyl-fructofuranose (MAF) and 1,6-diacyl-fructofuranose (DAF); (4) The mixture of step (3) is trans-esterified with an acyl donor in the presence of an immobilized enzyme to obtain 6-monoacyl-glucopyranose (MAG) and 1,6-diacyl-fructofuranose (DAF). Preparing a mixture comprising; and (5) 5-acyloxymethyl-2-furfural (5-acyloxymethyl-2-furfural (5- A method for preparing 5-acyloxymethyl-2-furfural including; preparing acyloxymethyl-2-furfural (AMF) is provided.

In addition, after step (4) of the method for producing 5-acyloxymethyl-2-furfural, (3') the mixture of step (4) is isomerized in the presence of an isomerase to obtain 6-monoacyl-glucopy preparing a mixture comprising lanose (MAG), 6-monoacyl-fructofuranose (MAF) and 1,6-diacyl-fructofuranose (DAF); and (4') trans-esterifying the mixture of step (3') with an acyl donor in the presence of an immobilized enzyme to obtain 6-monoacetyl-glucopyranose (MAG) and 1,6-diacetyl-fructofuranose (DAF). ), and the step (4) of the step (5) may be the step (4′).

In addition, in the method for producing 5-acyloxymethyl-2-furupural, the steps (3') and (4') are continuously repeated, and the steps (3') and (4') are continuously repeated. When further carried out repeatedly, the mixture of the step (4) of the step (3') may be the mixture of the step (4').

In addition, the steps (3') and (4') may be continuously repeated 1 to 15 times.

In addition, the isomerase of steps (1) and (3) may be a glucose isomerase.

In addition, the acyl donor of steps (2) and (4) may each independently be a compound represented by Structural Formula 1 below.

[Structural Formula 1]

In Structural Formula 1,

R ¹ is a C1 to C3 alkyl group;

이고,R ² is a C1 to C3 alkyl group, or

ego,

R ³ and R ⁴ are each independently a hydrogen atom or a C1 to C3 alkyl group.

In addition, the 5-acyloxymethyl-2-furfural may be 5-acetoxymethyl-2-furfural.

In addition, the immobilized enzymes in steps (2) and (4) may each independently include a lipase.

In addition, the steps (1) to (4) are each carried out as a solution reaction, and the solvent of the solution reaction is acetone, 1,4-dioxane, ethanol, ethyl acetate, ethyl ether, water, tetrahydrofuran and vinyl acetate. It may include one or more selected from the group consisting of.

In addition, the acid catalyst may include a solid acid catalyst.

In addition, the solid acid catalyst may be one in which a Bronsted acid or Lewis acid functional group is connected to an organic support or an inorganic support.

In addition, the solid acid catalyst may include a cation exchange resin.

In addition, the step (5) may be performed as a solution reaction, and the solvent of the solution reaction may include at least one selected from the group consisting of acetonitrile, 1,4-dioxane, dimethylformamide and dimethylsulfoxide.

In addition, the step (5) may be performed as a solution reaction, and the solvent of the solution reaction may include 100 parts by weight of the 1,4-dioxane and 5 to 20 parts by weight of an aprotic polar solvent.

In addition, the aprotic polar solvent may include at least one selected from the group consisting of dimethyl sulfoxide and dimethylformamide.

In addition, the aprotic polar solvent may include dimethylformamide.

In addition, the dehydration reaction of step (5) may be performed for 8 to 24 hours.

In addition, the isomerase, the immobilized enzyme, and the acid catalyst may be each independently immobilized on a carrier.

Also, the acid catalyst can be reused.

According to another aspect of the present invention, 5-acyloxymethyl-2-furfural prepared by the above production method is provided.

The method for producing 5-acyloxymethyl-2-furfural of the present invention has a simple reaction route, and a heterogeneous catalytic reaction using an immobilized enzyme and a cation exchange resin using an enzyme and a chemical catalyst. A hybrid reaction is used, separation and purification are easy, and the catalyst can be recycled, resulting in high economic efficiency.

In addition, the production method of the present invention has mild reaction conditions that do not use high temperature / high pressure, and efficiently 5-acyloxymethyl-2-furfural (5-acyloxymethyl-2-furfural (5- acyloxymethyl-2-furfural), in particular 5-acetoxymethyl-2-furfural (AMF).

1 is a graph showing the yield of DAF and fructose according to the type of lipase.
Figure 2 is a graph showing the yield of MAG and DAF according to the number of repetitions of isomerization and esterification reactions.
3 is a graph showing the yield of AMF and HMF according to a single solvent type.
Figure 4 is a graph showing the yield of AMF and HMF according to the type of dual solvent.
5 is a graph showing the yield of AMF and HMF according to the type of dual solvent and the dehydration time.

Since the present invention can apply various transformations and have various embodiments, specific embodiments are exemplified and described in detail in the detailed description. However, it should be understood that this is not intended to limit the present invention to specific embodiments, and includes all transformations, equivalents, and substitutes included in the spirit and scope of the present invention. In describing the present invention, if it is determined that a detailed description of related known technologies may obscure the gist of the present invention, the detailed description will be omitted.

Also, terms including ordinal numbers such as first and second to be used below may be used to describe various components, but the components are not limited by the terms. These terms are only used for the purpose of distinguishing one component from another. For example, a first element may be termed a second element, and similarly, a second element may be termed a first element, without departing from the scope of the present invention.

Also, when a component is referred to as "on another component," "formed on another component," "located on another component," or "layered on another component," that It should be understood that although it may be directly attached to, positioned on, or stacked on the front surface or one surface of another component, other components may further exist in the middle.

Singular expressions include plural expressions unless the context clearly dictates otherwise. In this application, the terms "include" or "have" are intended to designate that there is a feature, number, step, operation, component, part, or combination thereof described in the specification, but one or more other features It should be understood that the presence or addition of numbers, steps, operations, components, parts, or combinations thereof is not precluded.

In this specification, "hydrogen" means single hydrogen, double hydrogen, or tritium unless otherwise defined.

In the present specification, "alkyl (alkyl) group" means an aliphatic hydrocarbon group unless otherwise defined.

An alkyl group may be a "saturated alkyl group" that does not contain any double or triple bonds.

The alkyl group may also be an "unsaturated alkyl group" containing at least one double bond or triple bond.

Hereinafter, the method for preparing 5-acyloxymethyl-2-furfural of the present invention will be described.

First, glucose (D-Glucose) isomerization enzyme in the presence isomerization By isomerization reaction, glucose (D-Glucose) and D- Fructose (D-Fructose) Prepare a mixture containing (step 1).

Next, the glucose and D- of the mixture of step (1) fructose each cycled D- Glucopyranose (D- glucopyranose ) and D- Fructofuranose (D-fructofuranose) immobilized enzyme in the presence acyl donor ( acyl donor) and trans-ester reactions (trans- esterification reaction) 6- monoacyl - Glucopyranose (6-monoacyl-glucopyranose, MAG) and 1,6- diacyl - fructofuranose (1,6- Diacyl -fructofuranose, DAF) is prepared (step 2).

Next, the mixture of step (2) isomerization enzyme in the presence isomerization react 6- monoacyl - Glucopyranose (MAG), 6- monoacyl - fructofuranose (6- monoacyl -fructofuranose, MAF ) and 1,6- diacyl - Fructofuranose (DAF) Prepare a mixture containing (step 3).

Next, the mixture of step (3) is immobilized enzyme in the presence 6- by trans-esterification with an acyl donor monoacyl - Glucopyranose (MAG) and 1,6- diacyl - Fructofuranose (DAF) Prepare a mixture containing (step 4).

Finally, the 1,6- diacyl - Fructofuranose (DAF) acid catalyst in the presence 5- by dehydration reaction acyloxymethyl -2-furfural (5-acyloxymethyl-2-furfural, AMF) is prepared (step 5).

After step (4), (3') the mixture of step (4) is isomerized in the presence of an isomerase to form 6-monoacyl-glucopyranose (MAG) and 6-monoacyl-fructofuranose (MAF). ) and preparing a mixture comprising 1,6-diacyl-fructofuranose (DAF); and (4') the mixture of step (3') is trans-esterified with an acyl donor in the presence of an immobilized enzyme to obtain 6-monoacetyl-glucopyranose (MAG) and 1,6-diacetyl-fructofuranose (DAF). ), and the step (4) of the step (5) may be the step (4′).

When the steps (3') and (4') are continuously repeated and further performed, and the steps (3') and (4') are continuously and repeatedly performed, the step (3') The mixture of step (4) may be a mixture of step (4').

Steps (3') and (4') may be continuously repeated 1 to 15 times, preferably 2 to 10 times, and more preferably 3 to 7 times.

The isomerase of steps (1) and (3) may be a glucose isomerase.

The acyl donor of steps (2) and (4) may each independently be a compound represented by Structural Formula 1 below.

[Structural Formula 1]

In Structural Formula 1,

R ¹ is a C1 to C3 alkyl group;

이고,R ² is a C1 to C3 alkyl group, or

ego,

R ³ and R ⁴ are each independently a hydrogen atom or a C1 to C3 alkyl group.

The 5-acyloxymethyl-2-furfural may be 5-acetoxymethyl-2-furfural.

The immobilized enzymes of steps (2) and (4) may each independently include a lipase.

The steps (1) to (4) are each carried out as a solution reaction, and the solvent of the solution reaction is composed of acetone, 1,4-dioxane, ethanol, ethyl acetate, ethyl ether, water, tetrahydrofuran and vinyl acetate. It may contain one or more selected from the group.

The acid catalyst may include a solid acid catalyst.

The solid acid catalyst may be one in which a Bronsted acid or Lewis acid functional group is connected to an organic support or an inorganic support.

The solid acid catalyst may include a cation exchange resin.

The step (5) is performed as a solution reaction, and the solvent of the solution reaction may include at least one selected from the group consisting of acetonitrile, 1,4-dioxane, dimethylformamide and dimethylsulfoxide.

The step (5) is performed as a solution reaction, and the solvent of the solution reaction may include 100 parts by weight of the 1,4-dioxane and 5 to 20 parts by weight of an aprotic polar solvent.

The aprotic polar solvent may include at least one selected from the group consisting of dimethyl sulfoxide and dimethylformamide, preferably dimethylformamide.

The dehydration of step (5) may be performed for 8 to 24 hours.

The isomerase, immobilized enzyme, and acid catalyst may be each independently immobilized on a carrier.

The acid catalyst can be reused.

In addition, the present invention provides 5-acyloxymethyl-2-furfural prepared by the above preparation method.

[Example]

Hereinafter, the present invention will be described in more detail by way of examples. However, this is for illustrative purposes and the scope of the present invention is not limited thereby.

Example: Preparation of 5-acetoxymethyl-2-furfural (AMF)

Example 1

Glucose isomerization reaction

[Scheme 1]

Referring to Scheme 1, isomerization was performed in a 500 ml round bottom flask (RB) with magnetic stirring. 1.0 g of glucose was added to 100 ml of 10% H ₂ O in tetrahydrofuran (THF) as a solvent, and 1.0 g of glucose isomerase (GI) was added. An isomerization reaction was performed at 60° C. and 300 rpm for 15 hours to prepare glucose (D-Glucose, D-glucopyranose) and fructose (D-Fructose, D-fructofuranose).

After the reaction, glucose isomerase was separated using filter paper. The filtrate was evaporated on a rotary evaporator at 40° C. using a pressure pump to remove the solvent. However, H ₂ O in the solvent mixture still remains after evaporation because of its high boiling point. Since H ₂ O interferes with the trans-esterification reaction, H ₂ O must be removed after isomerization. The mixture was freeze-dried at -60 °C and 5 mbar for 24 hours to evaporate H ₂ O to obtain a crude product in the form of a white powder rather than a syrup form.

No other by-products could be observed during the glucose isomerization reaction. Also, referring to Scheme 2 below, isomerization of glucose by glucose isomerase was performed through Lobry-de Bruyn-van Ekenstein conversion.

[Scheme 2]

Trans-esterification reaction of glucose and fructose mixtures

[Scheme 3]

Referring to Scheme 3, after isomerization, trans-esterification of glucose and fructofuranose was performed simultaneously. 1.0 g of lipase, 100 ml of THF as a solvent and 1.54 ml of vinyl acetate (3 equiv) as an acyl donor were added to the RB. A trans-esterification reaction was performed at 60° C. and 300 rpm for 4 hours. After the reaction, lipase and solvent were removed using filter paper and an evaporator.

Thin layer chromatography (TLC) test and HPLC analysis using a mixture of chloroform, acetic acid, water (3 : 3.5 : 0.5) mixture as the eluent system revealed MAG (R _f = 0.36 and R _t = 9.42 min) from the trans-esterification reaction of glucose and fructose. ) and formation of DAF (R _f = 0.59 and R _t = 10.08 min).

During the reaction, most of the reactants, glucose and fructose, were converted to products after 4 hours. When glucose forms a pyranose ring by esterification, the primary as well as other secondary alcohol groups on the C6-carbon can be replaced with acetyl groups from acyl donors. In this case, two types of glucopyranose were synthesized, one being 6-monoacetyl-glucopyranose (MAG) that can be converted to DAF by isomerization and trans-esterification, and the other being isomer It is diacetyl-glucopyranose (DAG, R _f = 0.54) that does not react during nitration and dehydration reactions. DAG was retained as a by-product during all cycles and dehydration reactions in a yield of 9.94%. When MAG, DAG and DAF coexist in the product, they are difficult to separate using column chromatography due to similar physical properties.

Repeat isomerization and trans-esterification reactions

[Scheme 4]

Referring to Scheme 4, a mixture containing MAG and DAF was prepared by using 100 ml of 10% H ₂ O in tetrahydrofuran (THF) as a solvent and 1.0 g of glucose isomerase (GI) at 60° C. and 300 rpm for 15 hours. An isomerization reaction was performed to prepare a mixture comprising MAG, MAF and DAF.

[Scheme 5]

Referring to Scheme 5, a mixture containing MAG, MAF, and DAF was transduced at 60° C. and 300 rpm for 4 hours using 1.0 g of lipase, 100 ml of THF as a solvent, and 1.54 ml of vinyl acetate (3 equiv) as an acyl donor. A mixture containing MAG and DAF was prepared by esterification.

The above isomerization and trans-esterification reactions were repeated 5 times.

Dehydration of DAF and preparation of AMF

DAF obtained by repeating the isomerization and trans-esterification reaction 5 times was used as the starting material for the dehydration reaction. A cation exchange resin (CER), Amberlyst 15, was chosen as the acidic catalyst for the dehydration of DAF. AMF was prepared by using a DMF/Dioxane (1:9) mixture as a solvent and performing dehydration at 120° C. and 500 rpm using a magnetic bar for 16 hours.

Example 2

AMF was prepared in the same manner as in Example 1 except that the dehydration reaction was performed for 24 hours instead of the dehydration reaction for 16 hours in the dehydration of DAF and preparation of AMF in Example 1.

Example 3

The same method as in Example 1 except that a DMSO/Dioxane (1:9) mixture was used instead of a DMF/Dioxane (1:9) mixture as a solvent in the dehydration of DAF and the preparation of AMF in Example 1. AMF was prepared with

Example 4

In the dehydration of DAF and preparation of AMF in Example 1, a DMSO/Dioxane (1:9) mixture was used instead of a DMF/Dioxane (1:9) mixture as a solvent, and the dehydration reaction was performed for 16 hours instead of AMF was prepared in the same manner as in Example 1, except that dehydration was performed for 24 hours.

[Test Example]

Test Example 1: Comparison of fructose yield according to solvent type during glucose isomerization reaction

In order to compare the yield of fructose according to the type of solvent during the isomerization of glucose, 50 mg of glucose, 50 mg of glucose isomerase, and 5 ml of various organic solvents were used for isomerization at 60 ° C and 500 rpm for 15 hours. Yield of fructose compared. The yield of fructose was calculated using Equation 1 below, and the yield of fructose according to the type of solvent is shown in Table 1 below.

[Equation 1]

menstruum Fructose yield (%) Acetone 2.6 1,4-Dioxane 2.5 Ethanol 4.2 Ethyl acetate 0 Ethyl ether 0 Tetrahydrofuran (THF) 4.7 Vinyl acetate 0 water (H ₂ O) 49.8 Buffer pH 7 solution 29.4 1% H ₂ O in THF 4.7 5% H ₂ O in THF 63.8 10% H ₂ O in THF 67.2 15% H ₂ O in THF 37.6 20% H ₂ O in THF 19.78

Referring to Table 1, a small amount of fructose was found after isomerization in most organic solvents. Fructose was not completely formed only in ether and acetate solvents. However, in the case of a mixed solvent containing water, the fructose yield reached a maximum of 67.2%. These results show that the presence of water can greatly affect the isomerization reaction of the enzyme. In addition, the yield of fructose when using 5% H ₂ O in THF and 10% H ₂ O in THF as a solvent was improved compared to when only water was used as a solvent. In addition, the efficiency of pH was investigated by replacing the reaction medium by replacing water with phosphate buffer (pH = 7). However, the yield of fructose in phosphate buffer was 29.4%, lower than that of pure water (49.8%).

To determine the relationship between water and other organic solvents, the isomerization of glucose was tested under biphasic solvent conditions. Ethyl acetate and vinyl acetate, well known water immiscible solvents, were selected for the isomerization reaction. In the case of a two-phase solvent reaction, since the volume of H ₂ O is too small, H ₂ O is added after the reaction is complete and samples are taken from both phases for analysis. Glucose and fructose were found only in the water phase, and the results are shown in Table 2 below.

menstruum Fructose yield (%) 20% H ₂ O in Ethyl Acetate 43.7 10% H ₂ O in Ethyl Acetate 38.0 5% H ₂ O in Ethyl Acetate 33.2 1% H ₂ O in Ethyl Acetate 0 20% H ₂ O in Vinyl Acetate 36.5 10% H ₂ O in Vinyl Acetate 32.2 5% H ₂ O in Vinyl Acetate 34.2 1% H ₂ O in Vinyl Acetate 0

Referring to Table 2 above, the two-phase solvent system did not show better yield than the water solvent system.

The fructose yields of the two-phase solvent system of water and vinyl acetate and the two-phase solvent system of phosphate buffer (pH = 7) and vinyl acetate were compared, and the results are shown in Table 3 below.

Ratio of Vinyl Acetate(%) Fructose yield (%) H ₂ O Buffer pH 7 90 32.2 31.1 95 34.1 33.4 96 32.9 33.2 97 32.2 34.7 98 32.8 35.6 99 0 4.4

Referring to Table 3, it is shown that in the two-phase solvent system with a pH 7 buffer solution, glucose can form fructose in a yield similar to that in the two-phase solvent system with water. However, the two-phase solvent system does not significantly affect the fructose yield compared to the mixed solvent of water and THF.

test example 2: Depending on the type of lipase and solvent during esterification of fructose DAF yield comparison

In order to find the most suitable lipase for the trans-esterification reaction, various types of lipases were investigated. Esterification reaction was performed with 5 types of lipases. Esterification was performed at 60° C. for 4 hours using 50 mg of fructose, 50 mg of lipase, 0.077 ml of vinyl acetate, and 5 ml of solvent, and the results are shown in FIG. 1 .

Referring to FIG. 1, Novozym 435 showed remarkable selectivity for DAF synthesis, while other lipases left a large amount of by-products and unreacted fructose as well as DAF. In other words, Novozym 435 was the most suitable lipase for esterification. Indeed, Novozym 435 is a promising lipase and biocatalyst for esterification, glycerolysis and hydrolysis in biochemistry. Novozym 435 also has high temperature stability and resistance to organic solvents.

For optimization of the trans-ester reaction, a trans-ester reaction was performed at 60° C. and 500 rpm for 6 hours using 50 mg of fructose, 50 mg of lipase (Novozym 435), 0.077 ml (3 eq.) of vinyl acetate, and 5 ml of solvent under different solvent conditions. was monitored and the results are shown in Table 4 below. Samples were taken every hour and the yield was calculated.

menstruum DAF yield (%) 2h 3h 4h 5h 6h Acetone 44.9 45.8 44.4 47.0 47.6 1,4-Dioxane 90.3 86.9 94.3 89.4 88.4 Ethanol 0 0 0 0 0 Ethyl acetate 95.6 93.5 93.4 86.9 88.8 Ethyl ether 31.6 44.4 45.6 47.6 53.1 water (H ₂ O) 0 0 0 0 0 Tetrahydrofuran (THF) 89.3 92.5 96.4 95.2 80.2 Vinyl acetate* 68.2 84.2 85.4 90.4 91.7

* Vinyl acetate was used as the solvent, and the same ratio of vinyl acetate was added.

Referring to Table 4 above, most organic solvents show significant DAF yields with Novozym 435. In particular, 1,4-dioxane, THF, ethyl acetate, and vinyl acetate achieved a DMF yield of 90% or more. 1,4-dioxane, THF and ethyl acetate showed high yields of DAF, but the amount of DAF decreased after 5 hours of reaction. In addition, although the conversion rate of fructose was 100% up to 5 hours, the amount of by-products and fructose increased. In the case of water and ethanol, DAF formation was inhibited because of the hydroxy groups in these solvents. According to this result, THF was chosen as the ideal solvent for the 4-hour trans-esterification reaction.

test example 3: isomerization and MAG and following repetition of the trans-ester reaction. DAF's yield comparison

Figure 2 is a graph showing the yield of MAG and DAF according to the number of repetitions of isomerization and esterification reactions. Referring to Figure 2, after the first isomerization and esterification, the yields of MAG and DAF were 29.63% and 70.37%, respectively. There was still a lot of MAG left and this was another obstacle to the final yield of AMF. As a way to improve AMF yield, isomerization and esterification were repeatedly performed. MAF can be formed from MAG by a second isomerization under the same conditions as the first isomerization. MAG mixed with DAF gradually decreased. In addition, the subsequent esterification reaction was carried out in the same way as the first esterification reaction. Since MAF directly isomerized from MAG has a primary alcohol, MAF can be converted to DAF by a second trans-esterification reaction. Both processes were performed under exactly the same conditions as the respective first process. An iterative process can increase DAF yield and lower MAG. The isomerization and esterification reaction was repeated 5 times, and the solvent and enzyme were replaced with new ones after each reaction. The yield of DAF in the final product was 85.5%. Since the conversion of MAG to DAF between the 4th and 5th cycles was not significantly different, the isomerization and esterification reaction cycle was stopped in the 5th cycle.

test example 5: DAF's due to dehydration AMF Depending on the solvent in manufacturing with AMF HMF's yield comparison

For the synthesis of AMF, several polarities available at high reaction temperatures, such as dimethylformamide (DMF), dimethylsulfoxide (DMSO), acetonitrile (AN) and dioxane used for dehydration of hexose. Dehydration conditions were optimized with an organic solvent.

Dehydration from sugars to furan compounds was carried out with a chromium-based catalyst. However, considering the environmental problems of chromium-based catalysts, other catalysts for dehydration should be studied. As an alternative to heavy metal or noble metal based catalysts with high sugar dehydration efficiency, Amberlyst-15 was chosen. Amberlyst-15 has remarkable conversion, yield and reusability and has been used as a catalyst for the synthesis of HMF from fructose.

For the screening test, dehydration was performed at 120° C. for 6 hours using 50 mg of DAF, 5 ml of solvent, and 50 mg of Amberylst-15, and the results are shown in FIG. 3 . The yields of 5-acetoxymethyl-2-furfural (AMF) and 5-hydroxymethyl-2-furfural (HMF) were calculated using Equations 2 and 3 below.

[Equation 2]

[Equation 3]

Referring to FIG. 3, most of the solvents in the single solvent system showed poor AMF yields of 8.4 to 23.7%. In addition, it was confirmed that the single solvent system was not suitable for dehydration of DAF.

In particular, acetonitrile (81.6 °C) and dioxane (101.3 °C) have lower boiling points than the reaction temperature (120 °C) compared to DMF (153.0 °C) and DMSO (189.0 °C). As a solution, DMF and DMSO, which have a high boiling point and exhibit better yields for AMF formation, were added to acetonitrile and dioxane to stabilize the reaction conditions.

Using the same amount of DAF and Amberlyst-15, the reaction was performed in a mixture solvent system for 16 hours, and the results are shown in FIG. 4 . The reaction time was extended to 16 hours as the addition of DMF and DMSO delayed the reaction.

Referring to FIG. 4, a significant change in AMF yield was found in a mixture of dioxane and DMF or dioxane and DMSO. We expected that aprotic polar solvents such as acetonitrile, DMF and DMSO, which are widely used in the synthesis of HMF from fructose, would be suitable for dehydration of DAF. So, I focused on the use of DMSO and DMF. Although the yields of AMF and HMF in single dioxane were the lowest at 8.4% and 0.6%, respectively, the AMF yields of dioxane and DMF or mixtures of dioxane and DMSO were 57.7% and 64.9%, respectively, showing the highest yields. In particular, the maximum yields of AMF and HMF in the mixture of dioxane/DMSO (9:1) were 64.9% and 15.1%, respectively. It was found that the interaction of dioxane with an aprotic polar solvent can affect the dehydration reaction and dramatically improve the yield of AMF to over 50%.

When acetonitrile and DMF or acetonitrile and DMSO are mixed, the solvent mixture still has an unsuitable boiling point of 120°C. Even when the concentration of DMF and DMSO in dioxane or acetonitrile was higher than 10%, there was no significant difference in AMF yield.

The addition of DMF and DMSO can affect the formation of AMF and HMF as well as the thermal stability of the reaction due to the boiling point of dioxane below the reaction temperature. As a result, mixed solvents with low permittivity in the solvent medium can accelerate the overall reaction. In addition, DMSO and DMF can inhibit the side reaction of dioxane, which forms a by-product mainly from DAF. The yield of by-products in the mixture of DMF and dioxane was slightly higher than in the mixture of DMSO and dioxane.

MAG and DAF could not be separated by HPLC, TLC plate and column chromatography. Therefore, simultaneous dehydration of MAG and DAF mixtures was proposed to easily separate AMF and residue from the final product. MAG does not form other furanic compounds such as HMF after dehydration with an aprotic polar solvent and Amberlyst-15. Therefore, dehydration of MAG and DAF mixtures (14.5% and 85.5%) was performed under the same reaction conditions, and the results are shown in FIG. 5 .

Referring to FIG. 5, after 24 hours, the final yields of AMF and HMF reached 56.4% and 6.4% in the DMF/dioxane (1:9) mixture, respectively, and in the DMSO/dioxane (1:9) mixture. reached 53.4% and 6.5%, respectively. When reacted for 16 hours, dehydration was not completed due to the addition of DMSO. Compared to the DMSO/dioxane mixture, the DMF/dioxane mixture shows better yield and reaction rate than the DMSO/dioxane mixture.

In the above, the preferred embodiments of the present invention have been described, but those skilled in the art can add, change, delete or modify components within the scope not departing from the spirit of the present invention described in the claims. Various modifications and changes may be made to the present invention by addition or the like, which will also be included within the scope of the present invention. For example, each component described as a single type may be implemented in a distributed manner, and similarly, components described as distributed may be implemented in a combined form. The scope of the present invention is indicated by the following claims rather than the detailed description above, and all changes or modifications derived from the meaning and scope of the claims and equivalent concepts should be construed as being included in the scope of the present invention. do.

Claims (20)

(1) preparing a mixture containing glucose (D-Glucose) and D-fructose by isomerization reaction (isomerization reaction) of glucose (D-Glucose) in the presence of an isomerase;
(2) D-glucopyranose and D-fructofuranose in which glucose and D-fructose in the mixture of step (1) are cycled, respectively, are immobilized enzyme ) by trans-esterification reaction with an acyl donor in the presence of 6-monoacyl-glucopyranose (MAG) and 1,6-diacyl-fructofuranose Preparing a mixture containing (1,6-Diacyl-fructofuranose, DAF);
(3) Isomerization of the mixture of step (2) in the presence of isomerase to obtain 6-monoacyl-glucopyranose (MAG) and 6-monoacyl-fructofuranose (MAF) and 1,6-diacyl-fructofuranose (DAF);
(4) The mixture of step (3) is trans-esterified with an acyl donor in the presence of an immobilized enzyme to obtain 6-monoacyl-glucopyranose (MAG) and 1,6-diacyl-fructofuranose (DAF). Preparing a mixture comprising; and
(5) 5-acyloxymethyl-2-furfural (5-acyloxymethyl -Preparing 2-furfural, AMF);
A method for producing 5-acyloxymethyl-2-furfural comprising: According to claim 1,
After step (4) of the method for producing 5-acyloxymethyl-2-furfural,
(3') The mixture of step (4) is isomerized in the presence of an isomerase to obtain 6-monoacyl-glucopyranose (MAG), 6-monoacyl-fructofuranose (MAF) and 1,6- preparing a mixture comprising diacyl-fructofuranose (DAF); and
(4') The mixture of step (3') is trans-esterified with an acyl donor in the presence of an immobilized enzyme to obtain 6-monoacetyl-glucopyranose (MAG) and 1,6-diacetyl-fructofuranose (DAF) Preparing a mixture comprising a; Including,
The method for producing 5-acyloxymethyl-2-furfural, characterized in that the step (4) of the step (5) is the step (4'). According to claim 2,
The method for producing 5-acyloxymethyl-2-furupural
Steps (3') and (4') are further carried out continuously and repeatedly,
When the steps (3') and (4') are continuously repeated and further performed, the mixture of the step (4) in the step (3') is a mixture of the step (4') Method for producing 5-acyloxymethyl-2-furfural. According to claim 3,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that steps (3') and (4') are continuously repeated 1 to 15 times. According to claim 1,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that the isomerase in steps (1) and (3) is a glucose isomerase. According to claim 1,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that the acyl donors of steps (2) and (4) are each independently a compound represented by Structural Formula 1 below:
[Structural Formula 1]

In Structural Formula 1,
R ¹ is a C1 to C3 alkyl group;
R ² is a C1 to C3 alkyl group, or

ego,
R ³ and R ⁴ are each independently a hydrogen atom or a C1 to C3 alkyl group. According to claim 6,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that the 5-acyloxymethyl-2-furfural is 5-acetoxymethyl-2-furfural. According to claim 1,
The method for producing 5-acyloxymethyl-2-furfural, characterized in that the immobilized enzymes in steps (2) and (4) each independently contain lipase. According to claim 1,
The above steps (1) to (4) are each carried out as a solution reaction,
5-acyloxy, characterized in that the solvent of the solution reaction comprises at least one selected from the group consisting of acetone, 1,4-dioxane, ethanol, ethyl acetate, ethyl ether, water, tetrahydrofuran and vinyl acetate Method for producing methyl-2-furfural. According to claim 1,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that the acid catalyst comprises a solid acid catalyst. According to claim 10,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that the solid acid catalyst has a Bronsted acid or Lewis acid functional group connected to an organic support or an inorganic support. According to claim 10,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that the solid acid catalyst comprises a cation exchange resin. According to claim 1,
The step (5) is carried out as a solution reaction,
Preparation of 5-acyloxymethyl-2-furfural, characterized in that the solvent of the solution reaction contains at least one selected from the group consisting of acetonitrile, 1,4-dioxane, dimethylformamide and dimethylsulfoxide Way. According to claim 13,
The step (5) is carried out as a solution reaction,
The method for producing 5-acyloxymethyl-2-furfural, characterized in that the solvent of the solution reaction comprises 100 parts by weight of the 1,4-dioxane and 5 to 20 parts by weight of an aprotic polar solvent. According to claim 14,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that the aprotic polar solvent includes at least one selected from the group consisting of dimethylsulfoxide and dimethylformamide. According to claim 15,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that the aprotic polar solvent comprises dimethylformamide. According to claim 1,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that the dehydration of step (5) is carried out for 8 to 24 hours. According to claim 1,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that the isomerase, immobilized enzyme and acid catalyst are each independently immobilized on a carrier. According to claim 1,
A method for producing 5-acyloxymethyl-2-furfural, characterized in that the acid catalyst is reused. delete

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