KR101497969B1 - Method for preparing 5-acetoxymethylfurfural using solid phase synthesis - Google Patents

Abstract

A process for preparing 5-acetoxymethyl furfural is disclosed. The process for preparing 5-acetoxymethyl furfural of the present invention comprises reacting 5-halomethyl furfural with a solid support having an alkylammonium acetate salt introduced thereto to synthesize 5-acetoxy methyl furfural. The present invention can provide a method for producing 5-acetoxymethyl furfural which can be separated and purified easily after synthesis without using a separate base, and can easily recover and reuse the used solid resin through filtration have.

Description

METHOD FOR PREPARING 5-ACETOXYMETHYLFURFURAL USING SOLID PHASE SYNTHESIS < RTI ID = 0.0 >

The present invention relates to a process for producing 5-acetoxymethyl furfural, and more particularly, to a process for producing 5-acetoxy methyl furfural using a solid phase reaction, which is economical and highly efficient in reaction.

With the increase in global energy demand and the depletion of traditional energy sources, alternative energy development is now being watched. Among them, biomass is a renewable and quantitative biomass that has attracted much attention as seen in fuel production in biomass, an alternative energy development project conducted by the US Department of Energy. 5-hydroxymethylfurfural (HMF) is one of the biomass-derived substances that can replace the petrochemical-based basic compounds that have already been produced and used. have.

The synthesis of HMF is mainly reported through the dehydration reaction of hexane in the presence of a metal catalyst. However, they are difficult to be separated due to the use of a specific reaction solvent, commercialization due to difficult conditions such as anhydrous condition due to the use of a metal catalyst, There was a difficulty. As a method for solving this problem, the synthesis of 5-chloromethylfurfural, which is a precursor of HMF and its derivatives and has higher stability and higher synthesis yield, has been proposed by M. Mascal and EB Nikitin (Chem Sus Chem 2009, 2, 859;....... Angew Chem Int Ed 2008, 47, 7924).

5-acetoxymethylfurfural (AcHMF) is one of the main targets in the derivatization of HMF with CMF as the starting material. This is because it has high reactivity and polyfunctional structure due to its structural similarity with HMF, and has a large lipophilic property and is relatively stable. Therefore, it can replace HMF in the synthesis of monomers of furan family.

The method of synthesizing 5-acetoxymethyl furfural from 5-chloromethylfurfural was reported to use acetic acid and an inorganic base (US2008 / 221205 A1), but it has a disadvantage in that the yield is not high and practicality is poor Have. It has been reported that an improved yield can be obtained using an alkylammonium acetate salt in the process for preparing 5-acetoxymethyl furfural using 5-chloromethyl furfural as a starting material.

Efforts have been actively made to apply synthetic methods using solid resin reagents to the fields of pharmaceuticals and drug development worldwide. When a solid resin reagent is used, it is easy to separate and purify the reaction product, and the resin used can be easily recovered and reused by filtration. In addition, the process using such solid phase reagents is economical in terms of time and cost, and can be easily applied to industrial applications.

Therefore, if a solid-phase reaction can be efficiently applied to 5-acetoxymethylfurfural production method and mass production process is established to secure a raw material having a sufficiently low price, the demand range of 5-acetoxy methylfurfural as an industrial product .

SUMMARY OF THE INVENTION Accordingly, the present invention has been made in view of the above problems, and it is a first object of the present invention to provide a process for preparing 5-acetoxymethyl furfural which can be used as a platform compound.

A second object of the present invention is to provide an economical process for producing 5-acetoxymethyl furfural having a simple production process and a high reaction yield.

A third object of the present invention is to provide a process for producing 5-acetoxymethyl furfural which can use a biomass-derived material as a reaction raw material.

As a technical means for achieving the above technical object, the present invention relates to a process for producing 5-halomethyl furfural represented by the following formula 1 by reacting 5-halomethyl furfural with an alkylammonium acetate salt-introduced solid support, A process for preparing 5-acetoxy methyl furfural comprising the step of synthesizing methyl furfural is provided.

[Chemical Formula 1]

(2)

이다.In Formula 1, X is any one selected from a fluorine atom, a chlorine atom, a bromine atom and an iodine atom,

to be.

The alkylammonium acetate salt may be at least one selected from the group consisting of a primary ammonium acetate salt, a secondary ammonium acetate salt, a tertiary ammonium acetate salt, and a quaternary ammonium acetate salt.

 The solid-phase support into which the alkylammonium acetate salt is introduced may be at least one selected from the solid-phase supports represented by the following Formulas (3) and (4).

(3)

[Chemical Formula 4]

In the above formulas (3) and (4)

R and R 'are the same or different from each other and each independently represents a valence bond, a C1 to C15 straight chain alkylene group, or a C1 to C15 branched alkylene group,

R ¹ to R ⁴ are the same or different and are each independently a C1 to C10 straight chain alkyl group, a C3 to C10 branched alkyl group, or a C3 to C14 cycloalkyl group,

는

이고,

The

ego,

A and B are solid phase supports.

The solid support may be at least one selected from the group consisting of spherical synthetic resin particles having a porous structure and spherical inorganic particles.

The spherical synthetic resin particles may be at least one selected from the group consisting of polystyrene, styrene-divinylbenzene copolymer and polyethylene glycol-grafted polystyrene.

The spherical synthetic resin particles may be of a net structure or gel type.

The gel-type synthetic resin particles may have a degree of crosslinking of 1 to 10%.

The spherical inorganic particles may be at least one selected from the group consisting of silica, aluminum oxide, zirconium oxide and titanium oxide.

The amount of the alkylammonium acetate salt-introduced solid support may be 1 to 100 equivalents based on 1 equivalent of 5-halomethyl furfural represented by the formula (1).

 The step of synthesizing the 5-acetoxymethyl furfural may be carried out in an organic solvent.

 The organic solvent is selected from the group consisting of acetonitrile, propiononitrile, adiponitrile, benzonitrile dimethyl ether, diethyl ether, dipropyl ether, dichloroethyl ether, diisopropyl ether, n-butyl ethyl ether, diisobutyl ether, , Tetrahydrofuran, monochloromethane, dichloromethane, trichloromethane, tetrachloromethane, dichloromethane, trichloroethane, tetrachloromethane, dichloromethane, trichlorethylene, tetrachlorethylene, dichloropropane, trichloropropane, acetone, methyl ethyl Ketone, ethyl ethyl ketone, methyl acetate, ethyl acetate, propyl acetate and tert-butyl acetate.

 The step of synthesizing the 5-acetoxymethyl furfural may be carried out at -80 to 100 ° C.

 The step of synthesizing the 5-acetoxymethyl furfural can be carried out for 1 minute to 3 days.

Accordingly, the present invention can provide a method for producing 5-acetoxy methyl furfural which can be used as a platform compound such as HMF.

The present invention provides a process for the production of a 5-acetic acid solution, which can be easily separated and purified after synthesis and has a high reaction yield, can be easily recovered through filtration and reused, without using a separate base, A method for producing oxymethyl furfural can be provided.

The present invention can provide a process for producing 5-acetoxymethyl furfural which can use a biomass-derived material as a reaction raw material.

Hereinafter, embodiments and examples of the present invention will be described in detail so that those skilled in the art can easily carry out the present invention.

It is to be understood, however, that the following description is not intended to limit the invention to the particular 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.

The terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the invention. The singular expressions include plural expressions unless the context clearly dictates otherwise. In the present application, the terms "comprises ", or" having ", and the like, specify that the presence of stated features, integers, steps, operations, elements, or combinations thereof, But do not preclude the presence or addition of one or more other features, integers, steps, operations, elements, or combinations thereof.

Hereinafter, embodiments of the present invention will be described in detail. However, it should be understood that the present invention is not limited thereto, and the present invention is only defined by the scope of the following claims.

As used herein, an atomic bond means a single bond or a double bond, preferably a single bond.

As used herein, unless otherwise defined, the term "alkyl group" means a straight, branched or cyclic aliphatic hydrocarbon group. The alkyl group may be a "saturated alkyl group" which 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 may be a C1 to C20 alkyl group. More specifically, it may be a C1 to C10 alkyl group, a C1 to C6 alkyl group, or a C1 to C6 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.

As used herein, unless otherwise defined, the term "alkylene group" means a straight, branched or cyclic bivalent aliphatic hydrocarbon group. The alkylene group may be a "saturated alkylene group" which does not contain any double or triple bonds. The alkylene group may also be an "unsaturated alkylene group" comprising at least one double bond or triple bond. The alkylene group is a bivalent aliphatic hydrocarbon and may have two covalent bonds with a neighboring atom.

The alkylene group may be a C1 to C15 alkylene group. More specifically, it may be a C1 to C10 alkylene group, a C1 to C6 alkylene group or a C1 to C3 alkylene group.

5- Of acetoxymethyl furfural  Produce

As a technical means for achieving the above technical object, the present invention relates to a process for producing 5-halomethyl furfural represented by the following formula 1 by reacting 5-halomethyl furfural with an alkylammonium acetate salt-introduced solid support, Methylfurfural, comprising the step of synthesizing methylfurfural.

 [Chemical Formula 1]

(2)

In Formula 1, X is any one selected from a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom,

이다.In the above formula (2), AcO represents

to be.

The alkylammonium acetate salt may be at least one selected from the group consisting of a primary ammonium acetate salt, a secondary ammonium acetate salt, a tertiary ammonium acetate salt and a quaternary ammonium acetate salt in the solid phase support into which the alkylammonium acetate salt is introduced .

In the present specification, the primary ammonium acetate salt may be a salt in which one hydrogen of ammonium ion (NH ₄ ⁺ ) is substituted with an alkyl group and a primary ammonium ion is combined with an acetate ion.

In the present specification, the secondary ammonium acetate salt is a salt in which two hydrogen atoms of ammonium ion (NH ₄ ⁺ ) are both substituted with an alkyl group and a salt of acetate ion is combined, or two ammonium ions (NH ₄ ⁺ ) Hydrogen may be a single hydrocarbon group containing carbon which double bonds with nitrogen of ammonium ion or a salt in which a secondary ammonium ion substituted with a hetero hydrocarbon group is combined with an acetate ion.

In the present specification, the tertiary ammonium acetate salt is a salt in which the three hydrogen atoms of the ammonium ion (NH ₄ ⁺ ) are all bonded to the tertiary ammonium ion and the acetate ion substituted with an alkyl group, or two ammonium ions (NH ₄ ⁺ ) Hydrogen may be a hydrocarbon group substituted with a hydrocarbon group or a hydrocarbon group containing a double bond with nitrogen of an ammonium ion, or a salt in which a tertiary ammonium ion substituted with an alkyl group is substituted with an acetate group. A specific example of the tertiary ammonium acetate salt is 1-ethyl-3-methylimidazolium acetate.

In the present specification, the quaternary ammonium acetate salt is a salt in which quaternary ammonium ions in which all four hydrogen atoms of ammonium ions (NH ₄ ⁺ ) are substituted with alkyl groups are combined with acetate ions, or two ammonium ions (NH ₄ ⁺ ) Hydrogen may be a single hydrocarbon or hetero-hydrocarbon group containing carbon which carries a double bond with the nitrogen of the ammonium ion, and a salt in which a quaternary ammonium ion in which all two hydrogens are substituted with an alkyl group is combined with an acetate ion. A specific example of the quaternary ammonium acetate salt is 1-ethyl-3-methylimidazolium acetate.

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.

Specifically, the solid-phase support into which the alkylammonium acetate salt is introduced may be at least one selected from the solid-phase supports represented by the following general formulas (3) and (4).

(3)

[Chemical Formula 4]

In the above formulas (3) and (4)

R and R 'are the same or different from each other and each independently represents a valence bond, a C1 to C15 straight chain alkylene group, or a C1 to C15 branched alkylene group,

R ¹ to R ⁴ are the same or different and are each independently a C1 to C10 straight chain alkyl group, a C3 to C10 branched alkyl group, or a C3 to C14 cycloalkyl group,

는

이고,

The

ego,

A and B are solid phase supports.

The solid support may be spherical synthetic resin particles or spherical inorganic particles having a micro-porous structure.

The spherical synthetic resin particles may be made of synthetic resin such as polystyrene, styrene-divinylbenzene copolymer or polyethylene glycol-grafted polystyrene. The polyethylene glycol grafted styrene polymer may be crosslinked, and preferably has a low degree of crosslinking.

The synthetic resin particles may be of a net structure or a gel type. When the spherical synthetic resin particles are gel-type, the degree of crosslinking is preferably in the range of 1 to 10%. More preferably, the degree of crosslinking may be 1 to 5%, and even more preferably, the degree of crosslinking may be 1 to 3%.

The spherical inorganic particles may be silica, aluminum oxide, zirconium oxide, titanium oxide, or the like.

The amount of the synthetic resin to which the alkylammonium acetate salt is introduced may be 1 to 100 equivalents relative to 1 equivalent of 5-halomethyl furfural represented by the general formula (1). When the content is less than 1 equivalent, The yield is lowered, and if it exceeds 100 equivalents, the economical efficiency is lost.

In the present invention, the step of synthesizing the 5-acetoxymethyl furfural can be carried out in an organic solvent.

The organic solvent may be a solvent such as nitrile, ether, chloroalkane, ketone or ester compound. Specific examples thereof include acetonitrile, propionitrile, adiponitrile, benzonitrile dimethyl ether, diethyl ether, dipropyl ether, dichloroethyl Ethane, diisopropyl ether, n-butyl ethyl ether, diisobutyl ether, methylphenyl ether, tetrahydrofuran, monochloromethane, dichloromethane, trichloromethane, methane tetrachloride, ethane dichloride, trichloroethane, At least one selected from ethylene, trichlorethylene, tetrachlorethylene, dicarbonyl propane, trichloropropane, acetone, methyl ethyl ketone, ethyl ethyl ketone, methyl acetate, ethyl acetate, propyl acetate and tert-butyl acetate can be used.

The step of synthesizing 5-acetoxymethyl furfural may be carried out at -80 to 100 ° C, more preferably at 0 to 80 ° C. When the reaction is carried out at a temperature lower than -80 ° C, the reaction proceeds slowly, and when the reaction is carried out at a temperature higher than 100 ° C, the reaction proceeds too violently and a large amount of a side reaction can be produced.

The step of synthesizing the 5-acetoxymethyl furfural can be carried out for 1 minute to 3 days, more preferably 10 minutes to 24 hours. If the synthesis reaction time is less than 1 minute, all of the starting materials may not react. If the synthesis reaction time exceeds 3 days, by-products may be generated.

It will be appreciated by those skilled in the art that the reaction is generally carried out at normal pressure, but it may be carried out by changing the pressure and the reaction time and temperature may be appropriately adjusted according to the changed pressure.

The present invention is advantageous in that the 5-acetoxymethyl furfural produced using such a solid phase synthetic resin can be easily separated and purified, and the resin used can be easily recovered and reused through filtration.

The yield in the present invention is expressed by the following formula 1 unless otherwise stated.

[Formula 1]

Yield (%) = (actual yield / theoretical yield) X 100

The present invention can provide 5-acetoxymethyl furfural prepared according to the above-described preparation method.

Hereinafter, the structure of the present invention will be described more specifically by way of the following examples, but the present invention is not limited thereto.

[Example]

The present invention will be described in detail by way of examples, but the present invention is not limited to the following examples.

Example 1

4.8 mL of Amberite IRA-900 (macroreticular type, 650-820 ㎛, 1.0 meq./ml by wetted bed volume) resin in which the counter anion was replaced with acetate in chloride was swollen in dichloromethane and filtered. The filtered synthetic resin 4 ml of acetonitrile was added as an organic solvent, and 0.173 g (1.2 mmol) of 5-chloromethyl furfural (CMF, compound I) was dissolved and allowed to react at normal pressure and 50 ° C for one day. The mixture was filtered, the resin was washed with acetonitrile, and the reaction solution and the washing solution were collected and concentrated under reduced pressure to obtain 5-acetoxy methyl furfural (AcHMF, compound II) in the form of a pale yellow liquid. The yield of the product was 84%.

The pale yellow liquid was confirmed to be the target by 1H-NMR, and the analysis data are as follows.

AcHMF: 1H NMR (400 MHz, CDCl 3) 9.65 (s, 1H), 7.25 (d, J = 3.6, 1H), 6.62 (d, J = 3.6, 1H), 5.13 (s, 2H), 2.12 (s , 3H)

Example  2

2.6 mL of Amberite IRA-400 (gel type, 8% crosslinked, 600-750 μm, 1.4 meq./ml by wetted bed volume) resin in which the counter anion was replaced with acetate in chloride was swollen with dichloromethane and filtered. 4 ml of acetonitrile as an organic solvent was added to the filtered synthetic resin, and 0.133 g (0.92 mmol) of 5-chloromethyl furfural (CMF, compound I) was dissolved. The mixture was filtered, and the resin was washed with acetonitrile. The reaction solution and the washing solution were collected and concentrated under reduced pressure to obtain 5-acetoxymethyl furfural (AcHMF, Compound II) in the form of a pale yellow liquid. The yield of the product was 49%.

The pale yellow liquid was confirmed to be the target by 1H-NMR, and the analysis data are as follows.

AcHMF: 1H NMR (400 MHz, CDCl 3) 9.65 (s, 1H), 7.25 (d, J = 3.6, 1H), 6.62 (d, J = 3.6, 1H), 5.13 (s, 2H), 2.12 (s , 3H)

Nuclear magnetic  Resonance analysis

Nuclear magnetic resonance analysis was performed on Bruker's AVIII 400 (1H-400 MHz) after each product was dissolved in deuterated chloroform (CDCl ₃ ) containing 0.05% of internal standard tetramethylsilane (TMS).

As described above, the solid phase reaction using the synthetic resin in which the alkylammonium acetate salt is introduced in the present invention can easily separate and purify AcHMF having a high added value after synthesis, and can easily recover the used resin through filtration, .

It will be understood by those skilled in the art that the foregoing description of the present invention is for illustrative purposes only and that those of ordinary skill in the art can readily understand that various changes and modifications may be made without departing from the spirit or essential characteristics of the present invention. will be. It is therefore to be understood that the above-described embodiments are illustrative in all aspects and not restrictive. For example, each component described as a single entity may be distributed and implemented, and components described as being distributed may also be implemented in a combined form.

The scope of the present invention is defined by the appended claims rather than the detailed description and all changes or modifications derived from the meaning and scope of the claims and their equivalents are to be construed as being included within the scope of the present invention do.

Claims (13)

Reacting 5-halomethyl furfural represented by the following formula (1) with a solid-phase support having an alkylammonium acetate salt introduced thereto to synthesize 5-acetoxymethyl furfural represented by the following formula (2)
The step of synthesizing 5-acetoxymethyl furfural is carried out in an organic solvent at -80 to 100 캜,
The organic solvent is selected from the group consisting of acetonitrile, propiononitrile, adiponitrile, benzonitrile dimethyl ether, diethyl ether, dipropyl ether, dichloroethyl ether, diisopropyl ether, n-butyl ethyl ether, diisobutyl ether, , Tetrahydrofuran, monochloromethane, dichloromethane, trichloromethane, tetrachloromethane, dichloromethane, trichloroethane, tetrachloromethane, dichloromethane, trichlorethylene, tetrachlorethylene, dichloropropane, trichloropropane, acetone, methyl ethyl Ketone, ethyl ethyl ketone, methyl acetate, ethyl acetate, propyl acetate and tert-butyl acetate.
[Chemical Formula 1]

(2)

In Formula 1, X is any one selected from a fluorine atom, a chlorine atom, a bromine atom, and an iodine atom,
In the above formula (2), AcO represents

to be. The method of claim 1, wherein the alkylammonium acetate salt is at least one selected from the group consisting of a primary ammonium acetate salt, a secondary ammonium acetate salt, a tertiary ammonium acetate salt, and a quaternary ammonium acetate salt. A process for preparing oxymethyl furfural. The process for producing 5-acetoxymethyl furfural according to claim 1, wherein the solid-phase support into which the alkylammonium acetate salt is introduced is at least one selected from solid-phase supports represented by the following formulas (3) and (4)
(3)

[Chemical Formula 4]

In the above formulas (3) and (4)
R and R 'are the same or different from each other and each independently represents a valence bond, a C1 to C15 straight chain alkylene group, or a C1 to C15 branched alkylene group,
R ¹ to R ⁴ are the same or different and are each independently a C1 to C10 straight chain alkyl group, a C3 to C10 branched alkyl group, or a C3 to C14 cycloalkyl group,

The

ego,
A and B are solid phase supports. The method according to claim 1,
Wherein the solid support is at least one selected from the group consisting of spherical synthetic resin particles having a porous structure and spherical inorganic particles. The method of claim 4, wherein the spherical synthetic resin particles are selected from the group consisting of polystyrene, styrene-divinylbenzene copolymer, and polyethylene glycol-grafted polystyrene Acetoxymethyl furfural. ≪ / RTI > 5. The process for producing 5-acetoxymethyl furfural according to claim 4, wherein the spherical synthetic resin particles are of a net structure or gel type. 7. The process for producing 5-acetoxymethyl furfural according to claim 6, wherein the gel-type synthetic resin particles have a degree of crosslinking of 1 to 10%. 5. The method according to claim 4, wherein the spherical inorganic particles are at least one selected from the group consisting of silica, aluminum oxide, zirconium oxide, and titanium oxide. [Claim 5] The method according to claim 1, wherein the solid support having the alkylammonium acetate salt introduced thereinto is used in an amount of 1 to 100 equivalents based on 1 equivalent of 5-halomethyl furfural represented by Formula 1, A process for preparing oxymethyl furfural. delete delete delete The process for preparing 5-acetoxymethyl furfural according to claim 1, wherein the step of synthesizing 5-acetoxymethyl furfural is carried out for 1 minute to 3 days.