KR20220008528A - Method of preparing 5-acyloxymethyl-2-furfural from d-fructose using immobilized enzyme and solid acid catalyst - Google Patents

Abstract

Disclosed is a method for preparing 5-acyloxymethyl-2-furfural from d-fructose using an immobilized enzyme and a solid acid catalyst, in which a catalyst can be reused to increase economic efficiency. According to the present invention, the method comprises the following steps: (a) preparing a compound 2 of a reaction formula 1 by trans-esterification reaction between D-fructose, which is a compound 1, and an acyl donor in the presence of an immobilized enzyme; and (b) performing a dehydration reaction for the compound 2 in the presence of a solid acid catalyst to prepare a compound 3, which is 5-acyloxymethyl-2-furfural, wherein R1 is a C1 to C3 alkyl group.

Description

Method for producing 5-acyloxymethyl-2-furfural from D-fructose using immobilized enzyme and solid acid catalyst

The present invention relates to a method for preparing 5-acyloxymethyl-2-furfural, and more particularly, to 5-acyloxymethyl-2-furfural (5-acyloxymethyl-2-furfural (5- acyloxymethyl-2-furfural), in particular to a method for preparing 5-acetoxymethyl-2-furfural (AMF).

Fossil fuels have been developed since the 19th century and petroleum refining has advanced. Currently, many aspects of modern industry, from energy and bulk chemicals to refined materials, are dependent on petroleum, and thus these non-renewable resources are being consumed excessively. Recent research has shown great interest in using biomass resources as precursors for the production of polymers, organic chemicals and fuels.

5-acetoxymethylfurfural, particularly 5-hydroxymethyl-2-furfural (HMF) and its derivatives, are "carbon-neutral" in renewable and sustainable industries. It is one of the promising biomass-derived platform chemicals with potential to be feedstocks. Numerous studies on the synthesis of HMF from various carbohydrate sources have been conducted over the past 30 years.

However, in HMF separation, reactions using polar solvents such as N,N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), and sulfolane cause problems, and microwave heating, ionic liquids, or HMF synthesis process using special reaction conditions such as critical solvent is not suitable for commercialization at present due to high synthesis cost. In addition, due to the low melting point (30-34 ℃) of HMF and excellent miscibility in both hydrophilic and hydrophobic solvents, the options for the purification process are reduced, and there are problems in that it is difficult to obtain high purity due to difficult separation and purification.

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 by 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 preparing -furfural (5-acyloxymethyl-2-furfural), in particular 5-acetoxymethyl-2-furfural (AMF).

It is also an object of the present invention to have a mild reaction condition that does not use high temperature/high pressure, and to use a commercially available catalyst and a general-purpose solvent with low toxicity together with 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, as shown in Scheme 1, (a) compound 1 in the presence of an immobilized enzyme, D-fructose (D-Fructose) and an acyl donor are trans-ester (trans- esterification) to prepare compound 2; and (b) subjecting compound 2 to a dehydration reaction in the presence of a solid acid catalyst to prepare compound 3, 5-acyloxymethyl-2-furfural; containing 5-acyloxymethyl-2-furfural A method of manufacturing is provided.

[Scheme 1]

In Scheme 1,

R ¹ is a C1 to C3 alkyl group.

In addition, the acyl donor may be a compound represented by the following formula (4).

[Formula 4]

In Formula 4,

R ¹ is a C1 to C3 alkyl group,

이고,R ² is a C1 to C3 alkyl group, or

ego,

R ³ is a hydrogen atom or a C1 to C3 alkyl group.

According to another embodiment, in Formula 4, R ¹ is a methyl group, Compound 2 is 1,6-diacetyl fructose (DAF), and Compound 3 is 5-acetoxymethyl-2-furfural (AMF). ) can be

Also, the immobilized enzyme may be a lipase.

In addition, the immobilized enzyme may not be used or may be recycled by filtration after being used as a catalyst in the trans-ester reaction.

Also, step (a) is carried out as a solution reaction using a solvent, and the solvent in step (a) is water, methanol, ethanol, acetone, tetrahydrofuran, 1,4-dioxane, dimethyl sulfoxide, ethyl acetate, It may include at least one selected from the group consisting of methyl isobutyl ketone, hexane, and dichloromethane.

In addition, the solvent of step (a) may include at least one selected from the group consisting of tetrahydrofuran and 1,4-dioxane.

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

The cation exchange resin may also include Amberlyst 15.

In addition, step (b) is performed as a solution reaction using a solvent, and the solvent of step (b) may include at least one selected from the group consisting of tetrahydrofuran, 1,4-dioxane and dimethyl sulfoxide. .

In addition, the solvent of step (b) may include the 1,4-dioxane and the dimethyl sulfoxide, and 10 to 100 parts by weight of the dimethyl sulfoxide based on 100 parts by weight of the 1,4-dioxane. .

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

In addition, the solid acid catalyst may be unused or recycled after being used as a catalyst in the dehydration reaction.

In addition, in step (b), the weight ratio of the solid acid catalyst to the compound 2 (solid acid catalyst/compound 2) may be 0.5 to 1.

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

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

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

In addition, the production method of the present invention has a mild reaction condition that does not use high temperature/high pressure, and uses a commercially available catalyst and a general-purpose solvent with low toxicity to efficiently use 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 DAF yield and catalyst loss according to the number of reuse of the immobilized lipase of Example 3.
2 is a graph showing the yield and DAF conversion rate of AMF and HMF with time in the DAF dehydration reaction of Example 4-4.
3 is a graph showing the yield and DAF conversion rate of AMF and HMF according to Examples 5-1 to 5-7.
4 is a graph showing the yields of AMF and HMF according to Examples 5-2 and 5-8 to 5-11.
5 is a graph showing the yield of AMF and HMF according to the number of reuse of Amberlyst 15 of Example 7.

Since the present invention can apply various transformations and can have various embodiments, specific embodiments are illustrated and described in detail in the detailed description. However, this is not intended to limit the present invention to specific embodiments, and should be understood to include all modifications, 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 a related known technology may obscure the gist of the present invention, the detailed description thereof will be omitted.

In addition, terms including ordinal numbers such as first, second, etc. to be used below may be used to describe various elements, but the elements are not limited by the terms. The above terms are used only for the purpose of distinguishing one component from another. For example, without departing from the scope of the present invention, a first component may be referred to as a second component, and similarly, a second component may also be referred to as a first component.

Also, when it is stated that a certain component is “on another component,” “formed on another component,” “located on another component,” or “stacked on another component,” the It may be formed, positioned, or laminated by being directly attached to the front surface or one surface on the surface of other components, but it will be understood that other components may be further present in the middle.

The singular expression includes the plural expression unless the context clearly dictates otherwise. In the present application, terms such as “comprise” or “have” are intended to designate that a feature, number, step, operation, component, part, or combination thereof described in the specification exists, but one or more other features It should be understood that this does not preclude the existence or addition of numbers, steps, operations, components, parts, or combinations thereof.

As used herein, "hydrogen" means singlet, deuterium, or tritium, unless otherwise defined.

As used herein, the term "alkyl group" refers to an aliphatic hydrocarbon group unless otherwise defined.

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" containing at least one double bond or triple bond.

Hereinafter, a method for preparing 5-acyloxymethyl-2-furfural of the present invention will be described with reference to Scheme 1.

[Scheme 1]

In Scheme 1,

R ¹ is a C1 to C3 alkyl group.

First, the immobilized enzyme in existence Compound 1, D- D-Fructose and acyl donors ( acyl donor) to trans-esterification to prepare compound 2 (step a).

The acyl donor may be a compound represented by Formula 4 below.

[Formula 4]

In Formula 4,

R ¹ is a C1 to C3 alkyl group,

이고,R ² is a C1 to C3 alkyl group, or

ego,

R ³ is a hydrogen atom or a C1 to C3 alkyl group.

The immobilized enzyme may be lipase.

The immobilized enzyme may be unused or recycled by filtration after being used as a catalyst in the trans-ester reaction.

Step (a) is performed as a solution reaction using a solvent, and the solvent in step (a) is water, methanol, ethanol, acetone, tetrahydrofuran, 1,4-dioxane, dimethyl sulfoxide, ethyl acetate, methyl It may include one or more selected from the group consisting of isobutyl ketone, hexane, and dichloromethane, and preferably, may include one or more selected from the group consisting of tetrahydrofuran and 1,4-dioxane.

Finally, solid acid catalyst in existence Compound 3, 5-, by dehydration reaction of compound 2 acyloxymethyl Prepare -2-furfural (step b).

In Formula 4, R ¹ may be a methyl group, Compound 2 may be 1,6-diacetyl fructose (DAF), and Compound 3 may be 5-acetoxymethyl-2-furfural (AMF).

The solid acid catalyst may include a cation exchange resin.

The cation exchange resin may include Amberlyst 15.

Step (b) is performed as a solution reaction using a solvent, and the solvent of step (b) may include at least one selected from the group consisting of tetrahydrofuran, 1,4-dioxane, and dimethyl sulfoxide.

The solvent of step (b) may include the 1,4-dioxane and the dimethyl sulfoxide, and may include 10 to 100 parts by weight of the dimethyl sulfoxide based on 100 parts by weight of the 1,4-dioxane.

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

The solid acid catalyst may be unused or recycled after being used as a catalyst in the dehydration reaction.

In step (b), the weight ratio of the solid acid catalyst to the compound 2 (solid acid catalyst/compound 2) may be 0.5 to 1.

The immobilized enzyme and the solid acid catalyst may each independently be immobilized on a carrier.

The present invention also 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 thereto.

The reagents used in the Examples, D-Fructose (99%), 5-hydroxymethyl-2-furfural (HMF, 99%), 5-acetoxymethyl-2-furfural (AMF, 99%), vinyl acetate (99%), tetrahydrofuran (anhydrous, 99.9%, abbreviated as THF henceforth), 1,4-dioxane (anhydrous, 99.8%, abbreviated as dioxane henceforth), DMSO (anhydrous, 99.9%), sulfuric acid (H ₂ SO ₄ 95-98%) , p-toluenesulfonic acid monohydrate (pTSA, 98.5%), alumina (Al ₂ O ₃ , activated, acidic, Brockmann I), and Amberlyst 15 (hydrogen form, dry) were purchased from Sigma-Aldrich and used. Immobilized lipases such as Novozym 435 and Lipozyme TL IM were also purchased from Novozymes (Denmark), and Lipozyme RM IM was purchased from Sigma-Aldrich.

Example

Example 1: DAF Preparation

[Scheme 1]

Example 1-1

Referring to Scheme 1, 50 mg of D-fructose, 80 μL of vinyl acetate (3 equivalents), 50 mg of immobilized lipase Lipozyme TL IM as an immobilized enzyme, and _{5 mL of water (H 2} O) as a solvent were mixed at 45° C. for 5 hours at 300 rpm. It was reacted by magnetic stirring. After the reaction, lipase was filtered, and the filtrate was rotary evaporated and evaporated in vacuo to prepare a final product, DAF, in the form of a little yellow syrup.

¹ H NMR of DAF (300 MHz, CDCl ₃ ): 4.44-4.33 (m, 1H on C2), 4.30-4.23 (m, 2H of C5-CH ₂ ), 4.21-4.13 (m, 2H on C3 and C4) , 4.05-4.00 (m, 2H of C2-CH ₂ ), 2.17-2.12 (m, 6H of 2 -COOCH3; major anomer: 2.14 and 2.13; minor anomer: 2.17 and 2.12).

¹³ C NMR of DAF (300 MHz, DMSO-d ₆ ): 170.83-170.47 (d, 2C in -COO- groups), 100.86 (s, C5 in the ring), 78.85 (s, C2 in the ring), 76.49 (s, C4 in the ring), 75.57 (s, C3 in the ring), 66.16 (s, C6 in -CH ₂ group), 64.62 (s, C1 in -CH ₂ group), 21.04 (m, 2C in - CH ₃ groups)

LC-MS analysis with API-ES positive mode +70 V (in HCOOH 0.001 M), m/z: 282.2 (M + H ₂ O, 38%), 247.1 (M - OH ^- , 100%).

Examples 1-2 to 1-35

Example 1-1 in the same manner as in Example 1-1, except that the equivalents of the solvent, immobilized enzyme, and vinyl acetate described in Table 1 below were respectively used instead of the equivalents of the solvent, immobilized enzyme, and vinyl acetate of Example 1-1 DAFs were prepared by performing 1-2 to 1-35, respectively.

Table 1 below summarizes the types of solvents, types of immobilized enzymes, and equivalents of vinyl acetate used in the preparation of DAFs of Examples 1-1 to 1-35.

menstruum immobilized enzyme Vinyl acetate equivalent (equiv) Example 1-1 water (H ₂ O) Lipozyme TL IM 3 Example 1-2 water (H ₂ O) Lipozyme RM IM 3 Examples 1-3 water (H ₂ O) Novozym 435 3 Examples 1-4 MeOH Lipozyme TL IM 3 Examples 1-5 MeOH Lipozyme RM IM 3 Examples 1-6 MeOH Novozym 435 3 Examples 1-7 EtOH Lipozyme TL IM 3 Examples 1-8 EtOH Lipozyme RM IM 3 Examples 1-9 EtOH Novozym 435 3 Examples 1-10 Acetone Lipozyme TL IM 3 Examples 1-11 Acetone Lipozyme RM IM 3 Examples 1-12 Acetone Novozym 435 3 Examples 1-13 THF Lipozyme TL IM 3 Examples 1-14 THF Lipozyme RM IM 3 Examples 1-15 THF Novozym 435 3 Examples 1-16 1,4-Dioxane Lipozyme TL IM 3 Examples 1-17 1,4-Dioxane Lipozyme RM IM 3 Examples 1-18 1,4-Dioxane Novozym 435 3 Examples 1-19 DMSO Lipozyme TL IM 3 Examples 1-20 DMSO Lipozyme RM IM 3 Example 1-21 DMSO Novozym 435 3 Example 1-22 Ethyl acetate Lipozyme TL IM 3 Example 1-23 Ethyl acetate Lipozyme RM IM 3 Example 1-24 Ethyl acetate Novozym 435 3 Examples 1-25 MIBK Lipozyme TL IM 3 Example 1-26 MIBK Lipozyme RM IM 3 Example 1-27 MIBK Novozym 435 3 Example 1-28 Hexane Lipozyme TL IM 3 Example 1-29 Hexane Lipozyme RM IM 3 Examples 1-30 Hexane Novozym 435 3 Examples 1-31 Dichloromethane Lipozyme TL IM 3 Examples 1-32 Dichloromethane Lipozyme RM IM 3 Examples 1-33 Dichloromethane Novozym 435 3 Examples 1-34 THF Novozym 435 5 Examples 1-35 Dioxane Novozym 435 5

Example 2: DAF for manufacturing scale up (×10 times to ×600 times)

Example 2-1: THF solvent (×10 times)

D-fructose 0.5 g, vinyl acetate (3 equivalents) 800 μL, immobilized lipase Novozym 435 was reacted with the same weight (0.5 g) as D-fructose and 50 mL of THF as a solvent by magnetic stirring at 45° C. for 5 hours at 300 rpm. . After the reaction, lipase was filtered, and the filtrate was rotary evaporated and evaporated in vacuo to prepare a final product, DAF, in the form of a little yellow syrup.

Examples 2-2 to 2-5: THF solvent

Examples 2-2 to 2 in the same manner as in Example 2-1, except that 1.0 g, 1.5 g, 2.0 g, and 2.5 g of D-fructose were used instead of 0.5 g of D-fructose. -5 was performed to prepare DAF.

Example 2-6: THF solvent (×600 times)

Instead of using 0.5 g of D-fructose, use 30.0 g of D-fructose, use 46 mL of vinyl acetate (3 equiv) instead of 800 µL of vinyl acetate (3 equiv), and use 50 mL of THF as solvent. DAF was prepared by performing Example 2-6 in the same manner as in Example 2-1, except that THF 3L was used instead and magnetically stirred at 500 rpm for 6 hours instead of magnetically stirred at 300 rpm for 5 hours. did

Examples 2-7 to 2-11: 1,4-Dioxane solvent

DAF by performing each of Examples 2-7 to 2-11 in the same manner as in Examples 2-1 to 2-5, except that instead of using 50 mL of THF as a solvent, 50 mL of 1,4-dioxane was used. was prepared.

Example 3: Reuse of immobilized lipase (Novozym 435)

500 mg of D-fructose, 500 mg of immobilized lipase Novozym 435, 800 μL of vinyl acetate, and 50 mL of THF as a solvent were reacted with magnetic stirring at 300 rpm at 45° C. for 5 hours. After the reaction, lipase was filtered, and the filtrate was rotary evaporated and evaporated in vacuo to prepare a final product, DAF, in the form of a little yellow syrup.

This process was repeated 7 cycles. After each cycle, the lipase in the form of small beads was filtered, washed with THF and dried at room temperature for 12 hours before reuse.

Example 4: AMF preparation using a single solvent

[Scheme 2]

Example 4-1: Using THF as single solvent

Referring to Scheme 2, 50 mg of DAF, 50 mg of Amberlyst 15 as a solid acid catalyst, and 5 mL of THF as a solvent were reacted by stirring at 300 rpm at 120° C. for 8 hours. After the reaction, Amberlyst 15 was filtered, and AMF was isolated through vacuum distillation to prepare a final product, AMF.

¹ H NMR (300 MHz, THF-d ₈ ): 9.62 (s, 1H on -CHO), 7.31-7.30 (d, 1H of C4 on furan ring), 6.68-6.67 (d, 1H of C3 on furan ring) , 5.13 (s, 2H of -CH ₂ ), 2.06 (s, 3H of -CH ₃ ).

¹³ C NMR of AMF (300 MHz, THF-d ₈ ): 176.91 (s, C in -CHO group), 169.23 (s, C in -COO- group), 155.57 (s, C2 in the furan ring), 155.37 (s, C5 in the furan ring), 120.62 (s, C4 in the furan ring), 112.06 (s, C3 in the furan ring), 57.27 (s, C in -CH ₂ group), 19.32 (s, C in) -CH ₃ group).

GC-MS analysis with EI scan mode from -2.0 to +2.0 kV shows m/z: 282.2 (M - COCH ₃ + H+, 100%).

Example 4-2: Using 1,4-Dioxane as a single solvent

AMF was prepared in Example 4-2 in the same manner as in Example 4-1, except that 1,4-Dioxane was used instead of THF as a solvent.

Example 4-3: DMSO as single solvent

AMF was prepared in Example 4-3 in the same manner as in Example 4-1, except that DMSO was used instead of THF as a solvent.

Example 4-4: Using 1,4-Dioxane as a single solvent

Example 4-4 in the same manner as in Example 4-1, except that 10 mg of Amberlyst 15 was used instead of 50 mg of Amberlyst 15, and 1,4-Dioxane was used instead of THF as a solvent. was performed to prepare AMF.

Example 5: Preparation of AMF using a mixed solvent of 1,4-dioxane and DMSO

Example 5-1

50 mg of DAF, 50 mg of Amberlyst 15 as a solid acid catalyst, and 5 mL of a mixed solvent having a weight ratio of 1,4-dioxane and DMSO of 90:10 as a solvent were stirred at 120° C. for 8 hours at 300 rpm to react. After the reaction, Amberlyst 15 was filtered, and AMF was isolated through vacuum distillation to prepare a final product, AMF.

Examples 5-2 to 5-11

A mixed solvent of Example 5-1 in which the weight ratio of 1,4-dioxane and DMSO is 90:10, and a mixed solvent of 1,4-dioxane and DMSO mixed in the weight ratio shown in Table 2 below instead of 50 mg of Amberlyst 15 AMF was prepared by performing Examples 5-2 to 5-11 in the same manner as in Example 5-1, except that the amounts of , and Amberlyst 15 were used, respectively.

Table 2 below summarizes the weight ratio of the mixed solvent of 1,4-dioxane and DMSO used for preparing AMF of Examples 5-1 to 5-11, the amount of Amberlyst 15, and Amberlyst 15/DA.

Weight ratio of 1,4-Dioxane:DMSO Amberlyst 15
(mg) Amberlyst 15/DAF
(Cat/Sub, w/w, R) Example 5-1 90:10 50 One Example 5-2 85:15 50 One Example 5-3 80:20 50 One Example 5-4 75:25 50 One Example 5-5 70:30 50 One Example 5-6 60:40 50 One Example 5-7 50:50 50 One Examples 5-8 85:15 10 0.2 Examples 5-9 85:15 20 0.4 Examples 5-10 85:15 30 0.6 Examples 5-11 85:15 40 0.8

Example 6: AMF for manufacturing scale up (×10 times to ×100 times)

Example 6-1: (×10 times)

DAF 0.5g, Amberlyst 15 as a solid acid catalyst is Amberlyst 15/DAF (R _Cat/Sub ) of 0.6 in weight (0.3 g) and as a solvent 50 mL of a mixed solvent in which the weight ratio of 1,4-dioxane and DMSO is 85:15 was stirred at 300-500 rpm at 120° C. for 8 hours to react. After the reaction, Amberlyst 15 was filtered, and AMF was separated through vacuum distillation to prepare a final product, AMF.

Examples 6-2 to 6-5

Examples 6-2 to 6-5 were respectively carried out in the same manner as in Example 6-1, except that DAF 1.0g, 2.0g, 4.0g, 5.0g were used instead of DAF 0.5g. DAF was prepared.

Example 7: Amberlyst 15 Reuse

50 mg of DAF, 30 mg of Amberlyst 15, and 5 mL of a mixed solvent having a weight ratio of 1,4-dioxane and DMSO as a solvent of 85:15 were stirred at 120° C. for 8 hours at 300 rpm to react. After the reaction, Amberlyst 15 was filtered, and AMF was isolated through vacuum distillation to prepare a final product, AMF.

This process was repeated 5 cycles. After each cycle, the Amberlyst 15 was filtered, washed with acetone and dried in a vacuum oven (25° C.) before reuse.

[Test Example]

Test Example 1: Analysis of DAF yield according to solvent and lipase type

The yields of DAF prepared according to Examples 1-1 to 1-35 are shown in Table 3 below. The yield of DAF was calculated using Equation 1 below.

[Equation 1]

menstruum immobilized enzyme Vinyl acetate equivalent (equiv) DAF yield (%) Example 1-1 water (H ₂ O) Lipozyme TL IM 3 0.0 Example 1-2 water (H ₂ O) Lipozyme RM IM 3 0.0 Examples 1-3 water (H ₂ O) Novozym 435 3 0.0 Examples 1-4 MeOH Lipozyme TL IM 3 0.0 Examples 1-5 MeOH Lipozyme RM IM 3 0.0 Examples 1-6 MeOH Novozym 435 3 0.0 Examples 1-7 EtOH Lipozyme TL IM 3 0.0 Examples 1-8 EtOH Lipozyme RM IM 3 0.0 Examples 1-9 EtOH Novozym 435 3 0.0 Examples 1-10 Acetone Lipozyme TL IM 3 7.4±1.2 Examples 1-11 Acetone Lipozyme RM IM 3 0.0 Examples 1-12 Acetone Novozym 435 3 12.7±2.4 Examples 1-13 THF Lipozyme TL IM 3 44.3±2.7 Examples 1-14 THF Lipozyme RM IM 3 30.1±2.3 Examples 1-15 THF Novozym 435 3 96.2±2.8 Examples 1-16 1,4-Dioxane Lipozyme TL IM 3 37.4±3.2 Examples 1-17 1,4-Dioxane Lipozyme RM IM 3 22.5±1.8 Examples 1-18 1,4-Dioxane Novozym 435 3 90.4±2.5 Examples 1-19 DMSO Lipozyme TL IM 3 0.0 Examples 1-20 DMSO Lipozyme RM IM 3 0.0 Example 1-21 DMSO Novozym 435 3 0.0 Example 1-22 Ethyl acetate Lipozyme TL IM 3 9.1±2.1 Example 1-23 Ethyl acetate Lipozyme RM IM 3 0.0 Example 1-24 Ethyl acetate Novozym 435 3 14.4±2.2 Examples 1-25 MIBK Lipozyme TL IM 3 5.7±1.9 Example 1-26 MIBK Lipozyme RM IM 3 0.0 Example 1-27 MIBK Novozym 435 3 9.7±1.8 Example 1-28 Hexane Lipozyme TL IM 3 0.0 Example 1-29 Hexane Lipozyme RM IM 3 0.0 Examples 1-30 Hexane Novozym 435 3 0.0 Examples 1-31 Dichloromethane Lipozyme TL IM 3 0.0 Examples 1-32 Dichloromethane Lipozyme RM IM 3 0.0 Examples 1-33 Dichloromethane Novozym 435 3 0.0 Examples 1-34 THF Novozym 435 5 95.5±2.9 Examples 1-35 1,4-Dioxane Novozym 435 5 92.2±2.3

Referring to Table 3, when an ether-type solvent (THF or 1,4-dioxane) is used as a reaction medium, it can be seen that all three types of lipases can promote the trans-ester reaction. When Novozym 435 was used with THF or 1,4-dioxane, the yield of DAF in THF (Example 1-15) and 1,4-dioxane (Example 1-18) was 96.2% and 90.4%, respectively. The formation of DAF was most favorable.

On the other hand, in water (Examples 1-1 to 1-3) and solvents (Examples 1-4 to 1-9) containing -OH functional groups, -OH groups are primary groups of acetyl groups from acyl donors and D-fructose. Naturally, the trans-ester reaction did not occur because it interfered with the exchange of -OH groups.

Solvents with medium and low polarity indices obtained little or no DAF yield because they could hardly dissolve D-fructose (Examples 1-10 to 1-12, 1-22 to 1-33), and thus When D-fructose is not dissolved and comes into contact with immobilized lipase, the reaction remains stagnant.

It was also observed that the use of excess acyl donor (5 equivalents of vinyl acetate) did not improve the yield of DAF (Examples 1-34 and 1-35).

Therefore, THF and 1,4-dioxane were used as solvents for the scale-up procedure, and Novozym 435 was chosen as the catalyst.

Test Example 2: Analysis of scale-up results for DAF manufacturing

The types of solvents, the amount of D-fructose used, the D-fructose conversion, the DAF yield and the DAF selectivity of Examples 2-1 to 2-11 are shown in Table 4 below. The D-fructose conversion rate was calculated using Equation 2 below, the DAF yield was calculated using Equation 1 above, and the DAF selectivity was calculated using Equation 3 below.

[Equation 2]

[Equation 3]

menstruum D-fructose (g) scale up D-fructose conversion rate
(%) DAF yield
(%) DAF selectivity
(%) Example 2-1 THF 0.5 ×10 100 94.6 94.6 Example 2-2 THF 1.0 ×20 98.3 90.1 91.6 Example 2-3 THF 1.5 ×30 90.1 82.8 91.9 Example 2-4 THF 2.0 ×40 83.5 77.3 92.6 Example 2-5 THF 2.5 ×50 76.7 71.7 93.5 Example 2-6 THF 30.0 ×600 92.0 88.0 95.6 Example 2-7 1,4-Dioxane 0.5 ×10 100 91.3 91.3 Examples 2-8 1,4-Dioxane 1.0 ×20 95.7 86.7 90.6 Examples 2-9 1,4-Dioxane 1.5 ×30 88.8 80.2 90.3 Example 2-10 1,4-Dioxane 2.0 ×40 79.9 75.4 94.4 Example 2-11 1,4-Dioxane 2.5 ×50 73.4 69.4 94.6

The results in Table 4 above show that the scale-up had little effect on the conversion of D-fructose as well as the formation of DAF. Referring to Table 4, a DAF yield of 88.0% was achieved with a D-fructose conversion of 92% in a 600-fold scale-up reaction (Example 2-6) by slightly adjusting the reaction time and stirring speed. These results indicate that the trans-ester reaction of D-fructose using an immobilized enzyme catalyst is a fairly stable procedure and can be used for sustainable production of DAF. One major setback of this procedure is that when the concentration of the starting material is increased from 1% w/v to 5% w/v, the yield of DAF starts to decrease accordingly. A 22.9% yield decrease was recorded in THF and a 21.9% yield decrease in 1,4-dioxane. That is, it was difficult to achieve a high yield of DAF without completely dissolving D-fructose using a large amount of solvent in the initial state of the reaction.

test example 3: immobilized lipase ( Novozym 435) of according to the number of reuse DAF yield analysis

1 is a graph showing the DAF yield and catalyst loss according to the number of reuse of the immobilized lipase of Example 3. Referring to FIG. 1 , Novozym 435 can be reused up to 5 cycles with a weight reduction of less than 9%, and at this time, it was confirmed that the DAF yield was reduced to less than 5%, thereby providing a stable yield of DAF. Further reuse resulted in a higher reduction in DAF yield, with catalyst loss of more than 10% as well as 10.4% and 13.7% reduction in DAF yields after 6 and 7 reuses, respectively. The loss of catalyst can be explained by the partial fragmentation of catalyst beads during the long reaction and these fragments were lost during recovery and transfer between cycles. As observed in FIG. 1 , an increase in catalyst loss was associated with a decrease in DAF yield.

Test Example 4: Analysis of yields of AMF and HMF over time in the dehydration reaction of DAF

2 is a graph showing the yield and DAF conversion rate of AMF and HMF with time in the DAF dehydration reaction of Example 4-4. DAF diluted in 1,4-dioxane was heated at 120° C. and samples were taken at specific time intervals for HPLC analysis. Referring to FIG. 2 , both AMF and HMF were formed, and it was observed that AMF was the main product. After 8 hours, the highest AMF yield of 23.6% and HMF yield of 8.2% were achieved. Further prolongation of the response did not result in an increase in the amount of AMF. It was thought that the relatively low yield of AMF could be improved when the reaction conditions such as solvent medium or catalytic amount were adjusted. In addition, the simultaneous formation of AMF and HMF in the reaction medium suggested that both dehydration and hydrolysis were catalyzed in the presence of Amberlyst 15.

Test Example 5: Analysis of yields of AMF and HMF according to a single solvent type

Since DAF is synthesized and readily soluble in THF or 1,4-dioxane, it was tested whether these solvents are suitable for the dehydration reaction of DAF. DMSO was also investigated because, unlike HMF, AMF can be easily separated from DMSO by liquid-liquid extraction. The DAF conversion rate and the yield of AMF and HMF according to Examples 4-1 to 4-3 are shown in Table 5 below.

DAF conversion rate, AMF yield, and HMF yield were calculated using the following Equations 4 to 6, respectively.

[Equation 4]

[Equation 5]

[Equation 6]

menstruum DAF Conversion Rate (%) AMF yield (%) HMF yield (%) Example 4-1 THF 12.9±1.0 6.1±1.6 3.8±0.8 Example 4-2 1,4-Dioxane 51.2±1.2 29.2±2.1 15.6±1.7 Example 4-3 DMSO 59.2±1.4 38.7±2.4 14.9±1.9

Referring to Table 5, it was confirmed that THF as a dehydration solvent was worse than 1,4-dioxane and DMSO. It could be understood that this was because THF had a low boiling point (66 °C) and was not very effective for dehydration of DAF, and the dehydration of DAF was carried out at a much higher temperature (120 °C). The AMF yield in 1,4-dioxane was 23.6% (see FIG. 2) when 10 mg of Amberlyst 15 was used, and 29.2% when 50 mg of Amberlyst 15 was used. The yield did not improve significantly. When the amount of Amberlyst 15 was increased, the HMF yield in 1,4-dioxane was significantly pronounced from 8.2% to 15.6%. This may be an indication that the hydrolysis reaction in 1,4-dioxane is slightly more favorable when more acid catalyst is added.

Also, referring to Table 5, DMSO had the highest AMF yield, and DMSO was widely and effectively used as a solvent for dehydrating ketose-type sugars into furan compounds. Several studies have noted that DMSO can stabilize HMF and reduce side reactions during dehydration. Therefore, it could be understood that DMSO had a high total yield of HMF and AMF.

Test Example 6: Yield of AMF and HMF according to the weight ratio of the mixed solvent

Referring to Table 5, considering that 1,4-dioxane (101°C) has a much lower boiling point than DMSO (189°C), the AMF yield (29.2%) in 1,4-dioxane is DMSO It was not far behind when compared with the AMF yield (38.7%) in Therefore, DMSO and 1,4-dioxane were combined as a mixed solvent for further investigation with the aim of maximizing the yield of AMF while limiting the formation of HMF.

3 is a graph showing the yield and DAF conversion rate of AMF and HMF according to Examples 5-1 to 5-7. Referring to FIG. 3 , using DMSO as a mixed solvent greatly improved the formation of AMF while maintaining HMF in a low yield. The best condition was a solvent in which 15% DMSO in 1,4-dioxane was mixed, and the yields of AMF and HMF were 55.8% and 9.0%, respectively. The AMF yield started to decrease when the DMSO to 1,4-dioxane ratio was increased above 20%.

As mentioned that AMF and HMF were simultaneously formed during the reaction, when DMSO was mixed in a specific ratio in the mixed solvent, the mixed solvent had a positive effect on the dehydration of DAF into a furan compound. First, the added DMSO has the advantage of increasing the boiling point of the reaction medium, which makes the mixed solvent more suitable for dehydration at high temperatures (120° C.). Second, the presence of DMSO _{can have catalytic activity to remove H 2} O molecules from the furanose ring, as well as reduce the formation of by-products and stabilize the AMF and HMF formed in the reaction mixture.

Test Example 7: Yield of AMF and HMF according to the ratio of Amberlyst 15 and DAF

^{Since Amberlyst 15 is a H +} type cation exchange resin with a macro-reticular pore structure, in this case, the dehydration of DAF is heterogeneously catalyzed at hydrogen ion sites located throughout the resin bead. It is expected that higher amounts of catalyst will lead to better AMF yields for longer reaction times. With this in mind, the effect of the catalyst ratio on the dehydration reaction was investigated.

4 is a graph showing the yields of AMF and HMF according to Examples 5-2 and 5-8 to 5-11. Referring to FIG. 4, if the mass ratio between the catalyst/substrate is changed while maintaining the composition of the reaction medium in a mixed state of 15% DMSO in 1,4-dioxane, the catalyst/substrate ratio (R) is 0.6 to 1.0 (w/ w) had an AMF yield of 50% or more, and the formation of AMF was significantly improved and stabilized compared to using a low catalyst/substrate mass ratio. This means that when optimizing the procedure for sustainable production, it is possible to adjust the amount of catalyst slightly to lower the cost of the reaction.

Test Example 8: Analysis of scale-up results for AMF production

The amount of DAF, DAF conversion, AMF yield and HMF yield used in Examples 6-1 to 6-5 are shown in Table 6 below.

DAF (g) scale up DAF Conversion Rate (%) AMF yield (%) HMF yield (%) Example 6-1 0.5 ×10 69.9 54.7 9.8 Example 6-2 1.0 ×20 71.2 54.2 11.2 Example 6-3 2.0 ×40 73.8 56.1 13.7 Example 6-4 4.0 ×80 74.7 55.4 15.5 Example 6-5 5.0 ×100 74.9 57.9 15.8

Referring to Table 6, it was confirmed that it was possible to effectively scale-up up to 100 times without affecting the yield of the desired AMF product. As the amounts of DAF and Amberlyst 15 were increased while keeping the amount of solvent at a constant value, the stirring speed had to be slightly adjusted (range 300-500 rpm) for better thermal control during the entire reaction process.

Test Example 8: Yield of AMF and HMF according to the number of reuse of Amberlyst 15

5 is a graph showing the yield of AMF and HMF according to the number of reuse of Amberlyst 15 of Example 7. Referring to FIG. 5 , it was confirmed that Amberlyst 15 can be reused up to 5 cycles without significant change in the yield of AMF and HMF.

As mentioned above, although preferred embodiments of the present invention have been described, those of ordinary skill in the art can add, change, delete or The present invention may be variously modified and changed by addition, etc., and this 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 dispersed form, and likewise 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 above detailed description, and all changes or modifications derived from the meaning and scope of the claims and their equivalent concepts should be interpreted as being included in the scope of the present invention. do.

Claims (16)

As in Scheme 1,
(a) preparing compound 2 by trans-esterification of compound 1, D-fructose, and acyl donor in the presence of an immobilized enzyme; and
(b) dehydration reaction of compound 2 in the presence of a solid acid catalyst to prepare compound 3, 5-acyloxymethyl-2-furfural;
Method for producing 5-acyloxymethyl-2-furfural comprising:
[Scheme 1]

In Scheme 1,
R ¹ is a C1 to C3 alkyl group. According to claim 1,
Method for producing 5-acyloxymethyl-2-furfural, characterized in that the acyl donor is a compound represented by the following formula (4):
[Formula 4]

In Formula 4,
R ¹ is a C1 to C3 alkyl group,
R ² is a C1 to C3 alkyl group, or

ego,
R ³ is a hydrogen atom or a C1 to C3 alkyl group. 3. The method of claim 2,
In Formula 4,
R ¹ is a methyl group,
compound 2 is 1,6-diacetyl fructose (DAF),
A method for producing 5-acyloxymethyl-2-furfural, wherein compound 3 is 5-acetoxymethyl-2-furfural (AMF). According to claim 1,
The method for producing 5-acyloxymethyl-2-furfural, characterized in that the immobilized enzyme is lipase. According to claim 1,
The method for producing 5-acyloxymethyl-2-furfural, characterized in that the immobilized enzyme is not used or is filtered and recycled after being used as a catalyst in the trans-ester reaction. According to claim 1,
Step (a) is carried out as a solution reaction using a solvent,
1 selected from the group consisting of water, methanol, ethanol, acetone, tetrahydrofuran, 1,4-dioxane, dimethyl sulfoxide, ethyl acetate, methyl isobutyl ketone, hexane, and dichloromethane in step (a) A method for producing 5-acyloxymethyl-2-furfural, comprising more than one species. 7. The method of claim 6,
The method for producing 5-acyloxymethyl-2-furfural, wherein the solvent of step (a) comprises at least one selected from the group consisting of tetrahydrofuran and 1,4-dioxane. According to claim 1,
The method for producing 5-acyloxymethyl-2-furfural, characterized in that the solid acid catalyst comprises a cation exchange resin. 9. The method of claim 8,
The method for producing 5-acyloxymethyl-2-furfural, characterized in that the cation exchange resin comprises Amberlyst 15. According to claim 1,
step (b) is carried out as a solution reaction using a solvent,
A method for producing 5-acyloxymethyl-2-furfural, wherein the solvent of step (b) comprises at least one selected from the group consisting of tetrahydrofuran, 1,4-dioxane and dimethyl sulfoxide. 11. The method of claim 10,
The solvent of step (b) comprises the 1,4-dioxane and the dimethyl sulfoxide,
A method for producing 5-acyloxymethyl-2-furfural, comprising 10 to 100 parts by weight of the dimethyl sulfoxide based on 100 parts by weight of the 1,4-dioxane. According to claim 1,
The solid acid catalyst is a method for producing 5-acyloxymethyl-2-furfural, characterized in that a Bronsted acid or Lewis acid functional group is linked on an organic support or an inorganic support. According to claim 1,
The method for producing 5-acyloxymethyl-2-furfural, characterized in that the solid acid catalyst is not used or recycled after being used as a catalyst in the dehydration reaction. According to claim 1,
The method for producing 5-acyloxymethyl-2-furfural, characterized in that the weight ratio of the solid acid catalyst to the compound 2 (solid acid catalyst/compound 2) in step (b) is 0.5 to 1. 15. The method of claim 14,
The method for producing 5-acyloxymethyl-2-furfural, characterized in that the immobilized enzyme and the solid acid catalyst are each independently immobilized on a carrier. 5-acyloxymethyl-2-furfural prepared by the method of claim 1.

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