KR20150006800A - Method for preparing 2,5-diformylfuran from oxidation of 5-hydroxymethylfurfural using metal free catalyst and co-catalyst - Google Patents

Abstract

Disclosed is a method for preparing 2,5-diformylfuran through the oxidation of 5-hydroxymethylfurfural using a metal-free catalyst and a co-catalyst. The method for preparing 2,5-diformylfuran according to the present invention comprises the steps of preparing 5-hydroxymethylfurfural; preparing a metal-free catalyst and a co-catalyst; and oxidizing 5-hydroxymethylfurfural in step 1) in a low-boiling point solvent using the metal-free catalyst and the co-catalyst in step 2). The metal-free catalyst and the co-catalyst is used to allow the use of the low-boiling point solvent, shorten the reaction time, and lower the reaction time, thereby improving oxidation reaction conditions, thus enabling an economical and eco-friendly oxidation reaction and producing 2,5-diformylfuran at high yield.

Description

METHOD FOR PREPARING 2,5-DIFORMYLFURAN FROM OXIDATION OF 5-HYDROXYMETHYLFURFURAL USING METAL FREE USING METHOD FOR PREPARING 5-HYDROXYMETHYLFURFURAL USING A METHOD FOR PREPARING 5- CATALYST AND CO-CATALYST}

The present invention relates to a process for preparing 2,5-diformylfuran by oxidation of 5-hydroxymethyl furfural using a metal-free catalyst, a co-catalyst and a low boiling solvent .

5-hydroxymethyl furfural is a versatile intermediate which can be obtained in high yield from biomass such as natural carbohydrates including fructose, glucose, sugar and starch, and in particular is a conversion product of hexoses having 6 carbon atoms . Further, it is also possible to use a variety of compounds such as 2,5-diformylfuran, 5-hydroxymethylfuran-2-carboxylic acid, 5-formyl- Lt; / RTI > compounds.

2,5-Difformylfuran is an intermediate useful for preparing a large number of compounds per se. 2,5-Difformylfuran forms polypinacol and polyvinyl through polymerization and is used as a starting material in the synthesis of antifungal agents, drugs and ligands. 2,5-diformylfuran can also be used in the production of unsubstituted furan and is recognized as a useful substance in various aspects.

2,5-Difformylfuran has been previously prepared from 5-hydroxymethylfurfural using CrO ₃ and K ₂ CR ₂ O ₇ (L. Cottier et al., Org. Prep. Proced. Int (1995), 27 (5), 564]; JP 54009260). This process is expensive and produces large quantities of inorganic salt waste. Although heterogeneous catalysis using vanadium compounds has also been used, this catalyst has a low number of electrons (DE 19615878, Moreau, C. et al., Stud. Surf. Sci. Catal. 399-406).

Catalytic oxidation using expensive hydrogen peroxide (MPJ Van Deurzen, Carbohydrate Chem. (1997), 16 (3), 299) and nitrogen tetraoxide (JP 55049368) has been proven. While relatively inexpensive oxygen molecules (O ₂ ) have been used with Pt / C catalysts to form both 2,5-diformylfuran and furan-2,5-dicarboxylic acids (FDA) 4,977, 283), a small amount of 2,5-diformylfuran was obtained.

Various metal catalysts have been used to prepare 2,5-diformylfuran. However, depending on the use of a metal catalyst, it is necessary to maintain a high boiling point solvent and a high temperature for a long reaction time, Respectively.

Further, a method of producing 2,5-diformylfuran by a selective oxidation method of 5-hydroxymethylfurfural has been introduced, but it has been reported that a side reaction which is oxidized to a compound other than 2,5- reaction occurred.

Recently, it has been proposed to use 2,5-diformylfuran from 5-hydroxymethylfurfural using a metal-free catalyst such as 2,2,6,6-tetramethylpiperidine-1-oxyl free radical However, when a metal-free catalyst is used alone, a high boiling point solvent is required, resulting in a high energy cost, which is uneconomical. After the reaction, the purification of 2,5-diformylfuran and the purification of the solvent There is a problem that separation is difficult.

It is an object of the present invention to provide a process for producing 5-hydroxymethylfurfural by oxidation of 2,5-diformylfuran in a low-boiling solvent using a metal free catalyst and a co-catalyst, Temperature and short reaction time at high yields.

In addition, since a non-metal catalyst and a cocatalyst are used, it is possible to use a low boiling point solvent, so that it is easy to purify 2,5-diformyl furan and to separate a low boiling point solvent after 5-hydroxymethyl furfural oxidation, It is possible to prepare 5-diformylfuran.

The present invention also provides 2,5-diformylfuran by oxidizing 5-hydroxymethylfurfural in a low-boiling solvent using a metal-free catalyst and a cocatalyst.

The present invention provides a process for producing 2,5-diformylfuran comprising the step of oxidizing 5-hydroxymethylfurfural in a low-boiling solvent using a metal-free catalyst and a co-catalyst.

The method comprises the steps of (1) preparing a first reaction mixture by mixing 5-hydroxymethyl furfural with a metal-free catalyst using a low boiling solvent; And a step (step 2) of adding a co-catalyst to the first reaction mixture and reacting to prepare a second reaction mixture.

The process may further comprise separating the 2,5-diformylfuran from the reaction mixture according to step 2 above. The separation can be carried out by silica gel column chromatography using hexane and ethyl acetate.

The process may further comprise the step of purifying the 2,5-difformylfuran by separating the 2,5-diformylfuran (re-crystallization).

The metal-free catalyst may be a nitroxyl radical.

The metal-free catalyst may be 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl.

The co-catalyst may be bis (acetoxy) iodobenzene, acetic acid, or a mixture thereof.

The 5-hydroxymethyl furfural, non-metal catalyst,

The molar ratio of 5-hydroxymethyl furfural: metal-free catalyst: co-catalyst may be 1: 0.05-1: 0.2-2.

The low boiling point solvent may include at least one selected from the group consisting of ethyl acetate, dichloromethane, acetonitrile, diethyl ether, water, and toluene. More preferably ethyl acetate.

The low boiling point solvent may have a boiling point of 100 ° C or lower.

The oxidation reaction may be performed for 5 minutes to 120 minutes. More preferably 40 minutes to 60 minutes.

The oxidation reaction may be carried out at 30 to 75 ° C. More preferably at 30 < 0 > C to 40 < 0 > C.

The reaction can be carried out in an oxygen atmosphere, more preferably under an oxygen atmosphere of about 1 atmosphere.

The present invention also provides a process for producing 2,5-diformylfuran comprising the step of subjecting 5-hydroxymethyl furfural to an oxidation reaction in a low-boiling solvent using a porous non-metal catalyst and a co-catalyst.

The porous metal-free catalyst may be supported on a porous solid support with a silica nitroxyl radical.

The porous solid support may be porous silica.

The porous metal-free catalyst may be 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl supported on porous silica.

The porous metal-free catalyst may be a structure in which 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl is immobilized on porous silica. The immobilization may be performed through an organosilane linker.

The organosilane may most preferably be 3- (chloro) propyltriethoxysilane.

The porous metal-free catalyst may be prepared by reacting 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl with 3- (chloro) propyltriethoxysilane to give 3- (4- 2,2,6,6-tetramethylpiperidine-1-oxyl) propyl-propoxysilane; And silanizing the porous silica using the 3- (4-oxy-2,2,6,6-tetramethylpiperidine-1-oxyl) propyl-propoxysilane prepared in the above step .

The co-catalyst may be bis (acetoxy) iodobenzene, acetic acid, or a mixture thereof.

The 5-hydroxymethyl furfural, porous, metal-free catalyst and co-

The molar ratio of 5-hydroxymethyl furfural: porous non-metal catalyst: co-catalyst may be 0.5: 0.018 to 1: 0.75 to 0.8.

The low boiling point solvent may include at least one selected from the group consisting of ethyl acetate, dichloromethane, acetonitrile, diethyl ether, water and toluene.

The oxidation reaction step may be performed for 5 minutes to 120 minutes, and more preferably for 50 to 60 minutes.

The oxidation reaction may be carried out at 30 to 75 ° C, and more preferably 30 to 50 ° C.

The reaction may be carried out in an oxygen atmosphere. The oxygen atmosphere can be maintained at 1 atmosphere.

The porous silica may be SBA-15.

Also, the present invention provides 2,5-diformylfuran which is prepared by oxidizing 5-hydroxymethylfurfural in a low-boiling solvent using a metal-free catalyst and a co-catalyst.

The metal-free catalyst may be 4-hydroxy-2,2,6,6, -tetramethylpiperidine-1-oxyl.

The co-catalyst may be bis (acetoxy) iodobenzene, acetic acid, or a mixture thereof.

The metal-free catalyst and the co-catalyst may be used in a molar ratio of 0.05 to 1: 0.2 to 2 based on the mole of the 5-hydroxymethyl furfural used in the oxidation reaction.

The solvent may include one or more selected from the group consisting of ethyl acetate, dichloromethane, acetonitrile, diethyl ether, water, and toluene.

Also, the present invention provides 2,5-diformylfuran which is prepared by oxidizing 5-hydroxymethylfurfural in a low-boiling solvent using a porous nonmetal catalyst and a cocatalyst.

The porous metal-free catalyst may be 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl supported on porous silica.

The co-catalyst may be bis (acetoxy) iodobenzene, acetic acid, or a mixture thereof.

The 5-hydroxymethyl furfural, porous, metal-free catalyst and co-

The molar ratio of 5-hydroxymethyl furfural: porous non-metal catalyst: co-catalyst may be comprised between 0.5: 0.018 and 1: 0.75 to 0.8.

The low boiling point solvent may include at least one selected from the group consisting of ethyl acetate, dichloromethane, acetonitrile, diethyl ether, water, and toluene.

The porous metal-free catalyst may be a structure in which 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl is immobilized on the porous silica. The immobilization may be performed through an organosilane linker.

The porous metal-free catalyst may be prepared by a method of immobilizing 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl in a porous silica using an organosilane linker. The organosilane may most preferably be 3- (chloro) propyltriethoxysilane.

The porous metal-free catalyst may be prepared by reacting 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl with 3- (chloro) propyltriethoxysilane to give 3- (4- 2,2,6,6-tetramethylpiperidine-1-oxyl) propyl-propoxysilane; And silanization of the porous silica using the prepared 3- (4-oxy-2,2,6,6-tetramethylpiperidine-1-oxyl) propyl-propoxysilane can be prepared . The porous silica may be SBA-15.

The present invention also provides a method for preparing a porous metal-free catalyst by a method of immobilizing 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl on porous silica using an organosilane linker to provide.

The method comprises reacting a product obtained by reacting 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl with an organosilane with porous silica to silanise the porous silica . The organosilane may most preferably be 3- (chloro) propyltriethoxysilane.

Also, the method for producing the porous metal-free catalyst comprises reacting 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl with 3- (chloro) propyltriethoxysilane to obtain 3- (4 -Oxy-2,2,6,6-tetramethylpiperidine-1-oxyl) propyl-propoxy silane; And silanizing the porous silica using the 3- (4-oxy-2,2,6,6-tetramethylpiperidine-1-oxyl) propyl-propoxysilane prepared in the above step . The process may be a process for producing a porous, metal-free catalyst used in the production of 2,5-diformylfuran. The porous silica may be SBA-15.

The present invention also relates to a porous metal-free catalyst prepared according to the above process and used for the production of 2,5-diformylfuran, which comprises reacting 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl is immobilized on the surface of the support, and the immobilization is carried out through an organosilane linker.

The organosilane may most preferably be 3- (chloro) propyltriethoxysilane.

The porous silica may be SBA-15.

By using a metal-free catalyst and a co-catalyst in the production of 2,5-diformylfuran by the oxidation reaction of 5-hydroxymethyl furfural, it becomes possible to use a low-boiling solvent, shortening the reaction time, And the oxidation reaction conditions are improved. Thus, it is possible to produce 2,5-diformylfuran at a high yield as well as an economical and environmentally friendly oxidation reaction. Also, the yield of 2,5-diformylfuran can be improved remarkably by using the porous metal-free catalyst provided in the present invention. The porous metal-free catalyst is advantageous in that it does not decrease its activity even when it is reused several times and does not produce by-products in the course of the reaction. As a result, according to the present invention, it is possible to easily produce 2,5-diformylfuran on an industrial scale under mild conditions.

1 is a graph showing the effect of the reaction temperature of 5, 5-hydroxymethyl furfural, 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl and toluene - < / RTI > diformyl furan yield.
FIG. 2 shows the results of HPLC analysis of reaction products when a metal-free catalyst and / or an auxiliary catalyst were used in the oxidation reaction of 5-HMF.
FIG. 3 shows the mechanism by which 2,5-DFF is produced by oxidation of 5-HMF with 4-hydroxy-TEMPO and BAIB as catalysts.
4 is a graph showing the yield rate of 2,5-diformylfuran according to the change in the molar amount of 4-hydroxy-2,2,6,6, -tetramethylpiperidin-1-oxyl used (reaction conditions : Using 5-hydroxymethyl furfural and bis (acetoxy) iodobenzene in the same molar ratio, using dichloromethane as an organic solvent, reaction temperature 25-27 ° C).
5 is a graph showing the yield of 2,5-diformylfuran according to the change in the molar amount of bis (acetoxy) iodobenzene used (5-hydroxymethyl furfural and 4-hydroxy- 6,6, -tetramethylpiperidine-1-oxyl in a ratio of 0.2: 1, dichloromethane organic solvent, reaction at 25-27 DEG C for 45 minutes).
FIG. 6 is a graph showing the yield of 2,5-diformylfuran according to the kind of the low boiling point solvent (5-hydroxymethyl furfural, 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl and bis (acetoxy) iodobenzene in a molar ratio of 1: 0.2: 1.5, reacting at 25-27 ° C for 45 minutes.
FIG. 7 is a graph showing the yield of 2,5-diformylfuran according to the change of the reaction temperature (5-hydroxymethylfurfural, 4-hydroxy-2,2,6,6-tetramethylpiperidine 1-oxyl and bis (acetoxy) iodobenzene at a ratio of 1: 0.2 to 1.5: 1, using ethyl acetate as the organic solvent.
FIG. 8 is a graph showing the yield of 2,5-diformyl furan according to the amount of CH ₃ COOH input (5-hydroxymethyl furfural, 4-hydroxy-2,2,6,6-tetramethyl piperidine 1-oxyl and bis (acetoxy) iodobenzene at a ratio of 1: 0.2 to 1.5: 1, using ethyl acetate as the organic solvent.
FIG. 9 shows the result of NMR analysis of the separated light-purified 2,5-DFF ( ¹ H-NMR (CDCl _3, 400 MHz) d: 9.87 (s, 2H, CHO) ppm.)
Fig. 10 shows the synthesis process of TEMPO-SBA-15 catalyst.
11 shows the results of XRD analysis of SBA-15 as a solid support and TEMPO-SBA-15 catalyst supported on a solid support.
12 is a graph showing the N ₂ adsorption-desorption isotherm and pore size distribution curves (inset) of the solid support, SBA-15, and the catalyst TEMPO-SBA-15 supported on a solid support.
13 is a graph showing thermogravimetric curves obtained by analyzing SBA-15 and TEMPO-SBA-15 with a thermogravimetric analyzer.
14 shows FT-IR spectral analysis results of (a) PTES-TEMPO, (b) SBA-15 and (c) TEMPO-SBA-15.
15 is a SEM image of the morphologies of SBA-15 and TEMPO-SBA-15 (SEM image: (a) SBA-15, (b) TEMPO- : SBA-15, (d) TEMPO-SBA-15)
FIG. 16 is a graph showing the yield of 2,5-DFF depending on the presence or absence of oxygen (reaction conditions: 5-HMF (0.5 mmol), BAIB (0.75 mmol), ethyl acetate (solvent), RT, reaction time 1 h).
17 shows (a) GC-MS chromatogram of the oxides of HMF in a homogeneous TEMPO system (oxygen atmosphere) in which a 5-HMF oxidation reaction is performed using a TEMPO catalyst and (b) Spectrum peak.
Figure 18 shows GC-MS chromatograms of the oxides of HMF in a heterogeneous TEMPO system (oxygen atmosphere) in which a 5-HMF oxidation reaction is performed using a TEMPO-SBA-15 catalyst.
19 is a graph showing the yield of 2,5-DFF according to the type of co-catalyst under a heterogeneous TEMPO system in which a 5-HMF oxidation reaction is performed using a TEMPO-SBA-15 catalyst. (Reaction conditions as 5-HMF (0.5 mmol), TEMPO-SBA-15 (0.075 mmol), the secondary catalyst (Co-oxidants, 0.75 mmol) , ethyl acetate (solvent), RT, and the reaction time 1 h, O ₂ atmosphere Configuration)
FIG. 20 is a graph showing the results of 2,5-DFF yield analysis according to the reaction temperature under a heterogeneous TEMPO system in which a 5-HMF oxidation reaction is performed using a TEMPO-SBA-15 catalyst. (Reaction condition is 5-HMF (0.5 mmol), TEMPO-SBA-15 (0.075 mmol TEMPO), BAIB (0.75 mmol), ethyl acetate (solvent), composed of O ₂ atmosphere)
Figure 21 illustrates the effect of 5-HMF oxidation on the heterogeneous TEMPO system and the TEMPO catalyst to perform the 5-HMF oxidation reaction using the TEMPO-SBA-15 catalyst in a homogeneous TEMPO system. FIG. 5 is a graph showing the results of analysis on the yield of 2,5-DFF. (The reaction conditions are also composed of 5-HMF (0.5 mmol), TEMPO (0.075 mmol), BAIB (0.75 mmol), AcOH (0.05 mmol, if used), ethyl acetate (solvent), O ₂ atmosphere, and the reaction time 1h)
22 is a graph showing the results of testing the stability of TEMPO-SBA-15 by repeatedly using TEMPO-SBA-15 under the same reaction conditions. (Reaction condition is 5-HMF (0.5 mmol), TEMPO-SBA-15 (0.075 mmol TEMPO), BAIB (0.75 mmol), AcOH (0.05 mmol), ethyl acetate (solvent), O ₂ atmosphere, reaction temperature 40 ℃, Reaction time 1h)
FIG. 23 shows (a) an SEM image of TEMPO-SBA-15 before test according to FIG. 22 and (b) FT-IR spectrum.
FIG. 24 shows (a) an SEM image of TEMPO-SBA-15 after the test according to FIG. 22 and (b) FT-IR spectrum.
25 is a graph showing the yield of 5-HMF produced by hydrolysis of fructose in a one-port reaction from fructose to 2,5-DFF. (Reaction conditions: fructose (0.5 mmol), NbCl ₅ (0.1 mmol), solvent (DMSO, DMA, DMF), reaction temperature 80 ° C, reaction time 30 min)
26 is a graph showing the yield of 2,5-DFF in the oxidation reaction of 5-HMF according to FIG. (Reaction conditions are TEMPO-SBA-15 (0.075 mmol TEMPO), BAIB 0.75 mmol, solvent (DMSO, DMA, DMF), oxygen atmosphere, reaction temperature 25 ° C, reaction time 1 hour)

It is to be understood that both the foregoing general description and the following detailed description are exemplary and explanatory and are intended to be exemplary and explanatory only and not to be restrictive of the scope of the invention as defined by the appended claims. It will be obvious to those skilled in the art that these changes and modifications are within the scope of the appended claims.

Hereinafter, a preferred embodiment of the present invention will be described.

Example 1: Preparation of 2,5-diformylfuran

A method for preparing 2,5-diformylfuran (2,5-DFF) according to an embodiment of the present invention includes 5-hydroxymethyl furfural (5-HMF (2,5-diformylfuran, 2,5-DFF) is prepared by oxidation of a 5-HMF, and a metal-free catalyst, a co-catalyst and a low-boiling solvent are used for the oxidation reaction of 5-HMF.

The formulas of 5-HMF and 2,5-DFF are shown in the following formulas (1) and (2).

[Chemical Formula 1]

(2)

The metal-free catalyst may be 4-hydroxy-2,2,6,6-tetramethylpiperdine-1-oxyl, 4-hydroxy-2,2,6,6- 4-hydroxy-TEMPO). However, it is possible to select 5-HMF as a non-metal catalyst to enable oxidation reaction, but the present invention is not limited thereto. The formula of 4-hydroxy-TEMPO is shown in the following formula (3).

(3)

reagent

(97%), BAIB (98%), 4 (3-chloropropyl) -triethoxysilane, CPTES, 95%), poly (ethylene glycol) Poly (ethyleneglycol) -block-poly (propyleneglycol) -block-poly (ethyleneglycol), Pluronic® P123) and dry toluene (99.8%) were obtained from Sigma-Aldrich (South Korea) Lt; / RTI > 5-hydroxymethylfufural (98%), tetraethylorthosilicate (98%), sodium hydride (60% dispersion in oil), acetic acid and dry tetrahydrofuran (99.8% Organics. 2,5-diformylfuran (> 98%) was purchased from Tokyo Chemicals, Japan. HCl (35-37%) was purchased from Showa Chemicals. Dichloromethane, diethyl ether, acetonitrile, hexane, and ethyl acetate were purchased from Dae Jung Chemicals (South Korea). Sodium sulfate (99%) was purchased from Junsei Chemicals. All reagents were of reagent grade or higher and used directly without further purification. The reaction was carried out in a round bottom flask heat-treated in a temperature controlled oil bath. TLC (Thin-layer chromatography) was performed on silica gel 60 F ₂₅₄ plates _{(silica gel 60 F 254 plates,} Merck). Acros silica gel (0.075-0.250 mm, 150 A) was used for column chromatography.

5-HMF oxidation reaction

All experiments were carried out in a 2-necked round bottom flask. Initially purged with oxygen, and (if the test under oxygen atmosphere), and fixed to the balloon (O ₂ -filled balloon) filled with O ₂ (if the test under oxygen atmosphere). The flask was placed in a temperature controlled oil bath with magnetic stirring. 5-HMF, TEMPO catalyst (homogeneous for or TEMPO-SBA-15 / heterogeneous form), BAIB, and acetic acid (if used) were mixed in an appropriate solvent (10-15 mL). The reaction mixture was magnetically stirred at a controlled temperature for a period of time. Subsequently, in the case of using a heterogeneous catalyst, the reaction mixture was filtered to separate the solid catalyst. The filtrate or in homogeneous reaction was dried under reduced pressure and dissolved in deionized water. And then analyzed by HPLC (high pressure liquid chromatography).

One-pot conversion from fructose to 2,5-DFF.

Fructose and NbCl ₅ (niobium pentachloride) were reacted in a solvent (closed vessel) at 80 ° C for 30 minutes. After 30 minutes, a sample was obtained for HMF analysis and cooled to room temperature. The TEMPO-SBA-15 catalyst and BAIB were added to the vessel without a separation step. The reaction vessel was purged with oxygen, and (when they are reacted under an oxygen atmosphere), and fixed to the balloon (O ₂ -filled balloon) filled with O _2. The reaction was carried out at room temperature for 1 hour under the above conditions. After 1 hour, the reaction mixture was filtered to separate the solid catalyst. The filtrate was dried under reduced pressure, dissolved in deionized water and analyzed by HPLC (high pressure liquid chromatography).

Recycling of catalyst

After the oxidation reaction, TEMPO-SBA-15 was recovered from the reaction mixture through filtration. The used catalyst was washed with the reaction solvent to remove the traces of the reaction debris. The catalyst was then air-dried at room temperature prior to reuse.

Product analysis and quantification

Prior to HPLC analysis, the sample was filtered with a syringe filter (0.2 [mu] m Nylon). Waters HPLC equipped with a Waters 2414 refractive index detector maintained at 40 ° C and Biorad Aminex HPX-87H ion-exclusion column (300 x 7.8 mm) maintained at 60 ° C were used. A 5 mM H ₂ SO ₄ mobile phase was delivered at a flow rate of 0.6 mL min ^-1 . The concentration of 2,5-DFF (ie [DFF]) is the value for the calibration curves of the standard sample. The amount of produced 2,5-DFF (W _DFF ) and the corresponding reaction yield were calculated according to the following equations (1) and (2). V is the sample volume, MW is the molecular weight of 5-HMF (126.11 g / mole) or 2,5-DFF (124.09 g / mole). W _RM , W _AL , and W _HMF are the mass of the total reaction mixture, a partial sample for analysis, and the supplied HMF, respectively. All data are mean values of three reactions.

[Equation 1]

[Equation 2]

Isolation and purification of 2,5-DFF

For recovery of the purified 2,5-DFF product, the dried reaction sample (under reduced pressure) was analyzed by column chromatography using silica gel. Eluting with a mixture of EtOAc and hexane. 2,5-DFF was isolated using a mixture of 4% to 10% EtOAc in hexane based on the TLC results. The product containing the eluent was collected and the solvent was evaporated under reduced pressure to give a pale yellow crystalline material. The crystalline solid was washed with hexane and recrystallized in EtOAc to yield a white crystalline purity > 99% 2,5-DFF product (0.9884 g, isolated yield = 50.2%, yield from HPLC = 55.7% mp) 108 [deg.] C, lit. mp 108-110 [deg.] C). The pentenation of the product, 2,5-DFF, was confirmed by elemental analysis and ¹ H NMR analysis ( ¹ H NMR on a Varian 400 MHz NMR spectrometer in deuterated chloroform (CDCl ₃ ); see FIG. 9 and Table 2) .

Example 2: Preparation of heterogeneous catalyst

Manufacture of porous silica SBA-15

SBA-15 was prepared according to known methods (some modifications) using a tri-block copolymer (Pluronic®P123, Average MoI. Weight = 5800) as a structure directing agent (SDA). A 10 g sample of P123 was first dissolved in 325 mL of a mixture of deionized (DI) water and 60 mL HCl (35.0-37.0%), TEOS (20.6 g) was added, and then 800 lt; / RTI > The dispersion was allowed to stand at 40 DEG C for 24 hours and then left at 80 DEG C for another 24 hours. The solid product was filtered and washed repeatedly with warm deionized water (80 < 0 > C) to remove residual reactants. After air-drying at room temperature for 4 days, the dried powder was calcined at 500 ° C (in air, 5 h) (from room temperature to 2.5 ° C / min of heating rate).

Preparation of 3- (4-oxy-TEMPO) propyl-triethoxysilane

The reaction was carried out in a nitrogen atmosphere. Sodium hydride (0.2758 g, 6.9 mmol) was suspended in dry THF (20 mL) cooled in an ice-bath. A solution of 4-hydroxy-TEMPO (1.0 g, 5.8 mmol) in 5 mL dry THF was prepared and added dropwise to a cold NaH slurry. The mixture was stirred at room temperature to promote the reaction. After completing the gas evolution, the mixture was re-cooled at 0 ° C and CPTES (3- (chloro) propyl-triethoxysilane, 1.6615 g, 6.9 mmol) was added dropwise. The reaction was further allowed to proceed at room temperature for 48 hours. The crude product was recovered by evaporating the solvent under reduced pressure. The oily product precipitating the impurities was dissolved in diethyl ether. The filtered diethyl ether was dried over sodium sulfate and re-filtered. The solvent was removed from the rotary evaporator to obtain pure 3- (4-oxy-TEMPO) propyl-triethoxysilane (hereinafter PTES-TEMPO) (oily, dark orange).

Preparation of TEMPO-SBA-15 catalyst

The calcined SBA-15 (2.0 g) was vacuum-dried at 90 < 0 > C for 1 hour and vigorously stirred in 90 mL dry toluene under a nitrogen atmosphere to prepare a suspension. A solution of PTES-TEMPO (1.53 mmol) dissolved in toluene was added dropwise to the SBA-15 suspension. The mixture was refluxed with continuous stirring at 110 < 0 > C for 20 hours. The reaction was then terminated and cooled to room temperature. This was filtered, washed three times with toluene, and then air-dried at room temperature to prepare TEMPO-SBA-15.

Analysis of TEMPO-SBA-15 Catalyst Characteristics

SBA-15 and TEMPO were measured using a PANalytical EMPYREAN SWAX diffractometer (40 kV, 25 mA) with Ni-filtered Cu-Ka radiation (λ = 0.15406 nm) Powder low angle X-ray diffraction patterns of SBA-15 were analyzed. FT-IR spectra of the sample is between room temperature and 400, and the wave number 4000 cm ^-1 And analyzed using a Shimadzu IRPrestige-21 spectrophotometer. Thermogravimetric analysis (TGA) was performed with SCINCO TGA (N-1000) (35 ° C. to 1000 ° C., ramping rate 5 ° C./min, nitrogen 50 mL / min). N ₂ adsorption-desorption isotherms were analyzed with a Micromeritics ASAP-2020 surface area analyzer at 77K. Prior to the adsorption experiment, samples were in vacuo at 100 ° C for 24 hours. The nitrogen content of the sample was analyzed by elemental analysis using a Vario EL cube CHNS analyzer (Elementar Corporation, Germany). The morphology of the sample was analyzed by SEM (Hitachi S-3500N Scanning Electron Microscope) and FE-SEM (JEOL JSM-7600F Field Emission Scanning Electron Microscope).

Experimental Example 1: Analysis of yield of 2,5-DFF according to oxidation reaction of 5-HMF using a metal-free catalyst

The yield of 2,5-DFF according to the oxidation reaction of 5-HMF using a metal-free catalyst (4-hydroxy-TEMPO) was analyzed and is shown in FIG. 5-HMF and 4-hydroxy-TEMPO were used in the same molar ratio and toluene was used as a solvent. The yield of DFF was measured. As the reaction time continued from 0 hours to 48 hours, the yield of 2,5-DFF gradually increased, and when the reaction temperature increased from 30 to 120 ° C, the yield of 2,5-DFF was also increased . This is because the yield of 2,5-DFF is low due to the difficulty of forming the oxoammonium salt described later under the condition that the reaction time is short and the reaction temperature is low. However, when the reaction temperature is increased from 30 ° C. to 120 ° C., -HMF is oxidized. The yield increased with increasing reaction time at 80 ℃ or higher. The highest yield was obtained when reacted at 120 ℃ for 48 hours (44%). Considering that the use of a solvent having a low boiling point is efficient in the product recovery step, the low temperature reaction using a volatile solvent may be more suitable, and thus the experiment was not performed at a temperature exceeding 120 캜 in this analysis.

The oxidation reaction of 5-HMF is a step in which the TEMPO radical is oxidized to an oxoammonium salt and the 5-HMF is oxidized to 2,5-DFF due to the oxoammonium salt. The process by which the TEMPO radical is oxidized to the oxoammonium salt is shown in Scheme 1 below.

[Reaction Mechanism 1]

Experimental Example 2: Analysis of yield of 2,5-DFF by the oxidation reaction of 5-HMF with a metal-free catalyst and a cocatalyst

The product was analyzed by HPLC to confirm the effect of the metal-free catalyst and the cocatalyst on the yield of 2,5-DFF according to the oxidation reaction of 5-HMF. The results are shown in FIG. 2 ( A ) TEMPO: 1.0 mmol 5-HMF, solvent: toluene (120 ℃), 36 hours reaction, (B) 0.2 mmol TEMPO: 1.0 mmol 5-HMF: 1.5 mmol BAIB, in EtOAc (30 ℃) after 45min reaction). As shown in FIG. 2, although 4-hydroxy-TEMPO can be used as a catalyst in the oxidation reaction of 5-HMF, the reaction time and reaction temperature are not economical and the yield of 2,5-DFF is low It can be confirmed that a co-catalyst is required.

The co-catalyst may be bis (acetoxy) -iodobenzene (BAIB). However, it may be selected and used as a co-catalyst capable of oxidizing 5-HMF together with a metal-free catalyst, and is not limited to BAIB. The formula of BAIB is shown in the following formula (4).

[Chemical Formula 4]

Oxidation of 5-HMF using metal-free and co-catalyst

FIG. 3 shows the mechanism by which 2,5-DFF is produced by oxidation of 5-HMF with 4-hydroxy-TEMPO and BAIB as catalysts. In this mechanism, BAIB has two functions. First, it relates to the ligand exchange of the acetate group of BAIB and the primary alcohol group of 5-HMF (see FIG. 3 (B)). This results in the release of CH ₃ COOH derived from BAIB, which promotes initial dismutation in which the TEMPO radical (1) is converted to the oxoammonium salt (2) and the hydroxyamine (3) 3 (A)). The resulting oxoammonium salt (2) oxidizes 5-HMF to 2,5-DFF and is itself reduced to hydroxyamine (3). The second function of BAIB is to complete the oxidation cycle by regenerating the TEMPO radical (1) through oxidation of the hydroxyamine (3). Incidentally, as a by-product of hydroxyamine oxidation, CH ₃ COOH released from BAIB participates in a desmutation cycle in which the reproduced TEMPO radical (1) is converted into (2) and (3) .

Experimental Example 3: Effect of BAIB as a cocatalyst

As described above, since BAIB can regenerate TEMPO radicals, the amount of TEMPO usage can be significantly reduced to a catalytic level at the stoichiometric level. As shown in Table 1, when 5-HMF was reacted with a small amount of TEMPO and a stoichiometric amount of BAIB at room temperature for 4 hours, 34% 2,5-DFF was obtained (Entry 2). These results indicate that the addition of BAIB promotes 5-HMF oxidation even under mild conditions, even with TEMPO limited. That is, it indicates that the TEMPO radical is regenerated by BAIB. Referring to Figure 2 (B) HPLC chromatogram, CH ₃ COOH with 2,5-DFF is observed as the product. These results are consistent with the reaction mechanism described above (see FIG. 3). The CH ₃ COOH may be a by-product released upon TEMPO radical regeneration (see reaction mechanism 2 (B) above) or by a ligand exchange reaction of BAIB (see reaction mechanism 2 (A) above). The results described above mean that the amount of TEMPO used can be significantly reduced in the presence of BAIB.

Yield analysis of 2,5-DFF under various reaction conditions Entry 5-HMF (mmol) TEMPO
(mmol) BAIB
(mmol) CH ₃ COOH
(AcOH)
(mmol) Solvent Temp (캜) Time
2,5-DFF yield (%) One 1.0 1.0 - - Toluene 120 48 h 44 2 1.0 0.1 1.0 - DCM ^* RT 4 h 34 3 1.0 0.2 1.0 - DCM  RT 45 min 45 4 1.0 0.2 1.5 - DCM  RT 45 min 54 5 1.0 0.2 1.5 - EtOAc  30 45 min 56 6 1.0 1.0 - 1.0 EtOAc  30 45 min 40 7 1.0 0.2 - 1.0 EtOAc  30 45 min 2 8 1.0 0.2 1.5 0.1 EtOAc  30 45 min 66

* room temperature (25-27 ℃)

Experimental Example 4: Analysis of Product Yield According to Amount of Metal-Free Catalyst

To improve the yield of the product, the suitable amount of the metal-free catalyst was analyzed to what extent, and the results are shown in Fig. 4 shows the yield of 2,5-DFF with 1 mmol of 5-HMF and 1 mmol of BAIB at a 1: 1 molar ratio with varying amounts of 4-hydroxy-TEMPO at room temperature (25 ° C to 27 ° C) FIG.

In the case of 0.05 mmol of 4-hydroxy-TEMPO, the yield tended to increase with increasing reaction time, but the production rate of 2,5-DFF at the initial stage of reaction was relatively low. The maximum yield was 42% at the reaction time of 5 hours. In the case of the content of 4-hydroxy-TEMPO ≥ 0.1, the yield tends to decrease after achieving the maximum value. This may indicate that 2,5-DFF has been consumed or decomposed. But. No by-products or decomposition products were observed in the reaction sample. Thus, it can be seen that the 2,5-DFF produced is converted to other related compounds that are not analytically detected. As the amount of TEMPO increased, the time to achieve the maximum yield of 2,5-DFF tended to be shortened. This indicates that the content of 4-hydroxy-TEMPO has a direct influence on the kinetics of 2,5-DFF related reactions. Therefore, in order to maximize the 2,5-DFF recovery, it is desirable to terminate the reaction immediately after obtaining the maximum yield. In the above test, 0.2 mmol of 4-hydroxy-TEMPO and a maximum yield of 45% at a reaction time of 45 minutes were obtained.

Using co-catalysts such as BAIB with 4-hydroxy-TEMPO can produce 2,5-DFF under mild conditions. As shown in Table 1, the reaction time and the reaction temperature are remarkably reduced as compared with the case where 5-HMF is oxidized using only 4-hydroxy-TEMPO, which indicates that BAIB oxidizes the TEMPO radical to form oxoammonium And promotes the oxidation of 5-HMF by oxoammonium. It is also possible to use low-boiling solvents depending on the presence of BAIB. As the use of a low boiling point solvent is possible, the cost is reduced, and after the 5-HMF oxidation reaction, purification of 2,5-DFF and separation of a low boiling point solvent are facilitated, and pure 2,5-DFF can be obtained.

Experimental Example 5: Analysis of yield of 2,5-DFF according to the amount of cocatalyst

5-HMF and 0.2 mmol of 4-hydroxy-TEMPO were subjected to a yield analysis of 2,5-DFF according to the change of BAIB amount at room temperature (25 ° C to 27 ° C) using dichloromethane as a solvent, Respectively.

As the amount of BAIB increased from 0.05 mmol to 2 mmol, the yield of 2,5-DFF increased and the maximum yield was 54% at 1.5 mmol of BAIB. As the amount of BAIB used increases, the formation of oxoammonium by the TEMPO radical is increased by the acetic acid formed in the reaction, and BAIB increases the hydroxylamine (hydroxyamine) formed by the oxidation reaction of 5-HMF with oxoammonium, To help regenerate TEMPO radicals. However, if the amount of BAIB is increased over a certain amount, a large amount of acetic acid reacts with 5-HMF to become an esterified substance, thereby reducing the starting material of the oxidation reaction.

In order to produce 2,5-DFF by the oxidation reaction of 5-HMF, 5-HMF, 4-hydroxy-TEMPO as a metal-free catalyst and BAIB as a cocatalyst are mixed at a molar ratio of 1: 0.05-0.2: 0.2-2 , It may be preferable that the molar ratio is 1: 0.2 to 1.5, considering only the yield of 2,5-DFF. However, the present invention is not limited thereto, and it is possible for the ordinary technician to carry out the modification in consideration of economical efficiency and the like.

Experimental Example 6: Analysis of yield of 2,5-DFF by reaction solvent

5-HMF, 4-hydroxy-TEMPO and BAIB were used at a molar ratio of 1: 0.2: 1.5, and the yield of 2,5-diformylfuran was analyzed according to the change of solvent. The reaction was carried out at room temperature for 45 minutes.

In the present invention, ethyl acetate (EtOAc), dichloromethane (DCM), acetonitrile (ACN), diethyl ether (Et ₂ O), which is a low boiling point solvent having a boiling point of about 100 ° C or less, ) And water (water, H ₂ O), respectively, were used to determine the yield of 2,5-DFF, but the choice was made to allow oxidation of 5-HMF with a metal-free catalyst and co-catalyst as a low boiling solvent And is not necessarily limited to these. DCM and EtOAc. The maximum yield of 2,5-DFF was 56% in EtOAc. The yields of ACN and Et ₂ O were 44% and 32%, respectively. These results indicate that the use of non-polar and polar aprotic solvents with good solubility for the reactants is suitable for this reaction. Quantum solvents such as water showed a low yield of 18%. In an aqueous system, BAIB can be hydrolyzed to iodosylbenzene (PhI = O) and thus a secondary oxidant that can be used for TEMPO radical regeneration may be deficient. Since EtOAc has a low boiling point and exhibits a maximum yield of 2,5-DFF (Table 1, Entry 5), EtOAc in the solvents listed above is most suitable for 4-hydroxy-TEMPO / BAIB-mediated 5-HMF oxidation .

As described above, in the present invention, a solvent having a low boiling point is used, which minimizes the risk of solvent volatilization and can be efficient in the product recovery step. That is, in the case of a solvent having a low boiling point, the solvent can be easily removed, so that the energy required for purification of the product can be minimized.

Experimental Example 7: Yield Analysis According to Effect of Reaction Temperature

5-HMF, 4-hydroxy-TEMPO, and BAIB at a molar ratio of 1: 0.2: 1.5 were analyzed by using an ethyl acetate solvent. The results are shown in FIG. 7 .

As the reaction temperature increased, the initial yield was high, but the yield tended to decrease as the reaction proceeded. At 60 ° C or higher, the yield was low because acetic acid formed in the reaction mixture could undergo esterification with 5-HMF at high reaction temperatures.

The highest yields of 2-DFF were obtained when the reaction temperature was 30 ° C and the reaction time was 45-60 minutes. This indicates that the oxidation reaction of 5-HMF at room temperature is possible, which is an economical cost saving effect. The oxidation reaction of 5-HMF may be performed for 5 minutes to 120 minutes and preferably for 45 to 60 minutes. The oxidation reaction of 5-HMF may be performed at 30 ° C to 75 ° C and preferably at room temperature of 30 ° C or so.

Experimental Example 8: Role of acetic acid in 5-HMF oxidation

As shown in Table 1 above, 40% 2,5-DFF was obtained when the same molar amounts of 4-hydroxy-TEMPO and CH ₃ COOH were reacted. This indicates the importance of CH ₃ COOH in the TEMPO radical denaturation to generate the oxoammonium salt involved in 5-HMF oxidation. However, even when sufficient CH ₃ COOH is added, the yield of the oxoammonium salt may be lowered when the amount of 4-hydroxy-TEMPO added is low in a reaction in which BAIB is not added. Further, when the amount of 4-hydroxy-TEMPO is low, the yield of 2,5-DFF is lowered (Table 7 Entry 7). This means that the addition of only CH ₃ COOH without addition of BAIB is not sufficient for yield. In addition, the reaction of BAIB and 5-HMF proceeded without the TEMPO addition, but no 2,5-DFF was obtained and no CH ₃ COOH was generated because the main oxidant was not present. This indicates that the process of FIG. 3 (B) has not proceeded effectively. These results indicate that BAIB may not be a reliable source of CH ₃ COOH required for initial TEMPO radical demethylation. The effect of CH ₃ COOH input was analyzed and shown in FIG. As a result of the analysis under the optimum TEMPO / BAIB reaction condition described above, it was confirmed that the 2,5-DFF yield was improved by adding a small amount of CH ₃ COOH. The highest yield of 2,5-DFF was found to be 66% when 0.1 mmol of CH ₃ COOH was added (Table 1, Entry 8). These results indicate that it is necessary to add CH ₃ COOH to the TEMPO / BAIB system to promote the TEMPO radical dimention and thus to improve the yield of 2,5-DFF. 5-HMF was oxidized to obtain 2,5-DFF (0.9884 g) which was purified by silica-gel column chromatography and then analyzed by proton NMR. The purity was confirmed by elemental analysis The results are shown in FIG. 9 and Table 2. 9 is a ¹ H-NMR result ( ¹ H-NMR (CDCl _3, 400 MHz) d: 9.87 (s, 2H, CHO), 7.35 (s, 2H, furan H)

Elemental analysis of isolated and purified 2,5-DFF Element  Theoretical (%)  Found (%)   C 58.1 58.4   H 3.2 3.2   O 38.7 38.4

Experimental Example 9: Characterization of TEMPO catalyst supported on a porous support

A TEMPO catalyst supported on a porous solid support such as SBA-15 was prepared and applied to the oxidation reaction of 5-HMF to 2,5-DFF.

Porous silica support SBA-15 was prepared by TEOS (tetraethylorthosilicate) hydrolysis under triblock co-polymer P123, EO20PO70EO20 as a surfactant. To form PTES-TEMPO (3- (4-oxy-TEMPO) propyl-triethoxysilane), 4-hydroxy-TEMPO was etherified with CPTES (3- (chloro) propyl-triethoxysilane). PTES-TEMPO was used to silane support SBA-15. In this reaction, a covalent bond Si-O-Si bond was formed by reaction of silanol groups of SBA-15 having an ethoxy group of PTES-TEMPO (see FIG. 10).

Tissue characteristics of SBA-15 are X- ray diffraction (XRD) patterns and N ₂ adsorption-desorption isotherms were analyzed _{(N 2 adsorption-desorption isotherms)} . As shown in FIG. 11, SBA-15 (bare support material) exhibited three well-resolved diffraction peaks at 2? = 0.858 ?, 1.482 ?, and 1.703 ?. This is consistent with the reflection planes 100, 110 and 200. These peaks show that the long-range order exists in SBA-15 and that SBA-15 has a well-formed two-dimensional hexagonal meso-structure. will be. After immobilization, the obtained TEMPO-SBA-15 showed diffraction peaks at 2θ = 0.858 ㅀ, 1.508 ㅀ and 1.742 유사, similar to SBA-15. This indicates that the two-dimensional hexagonal meso-structure of SBA-15 did not deteriorate after immobilization of PTES-TEMPO. The TEMPO-SBA-15 thus prepared exhibited a reflective surface similar to that of the support, meaning that it had a regular porous structure. A decrease in diffraction peak intensity consistent with reflective surface 100 indicates that PTES-TEMPO was successfully immobilized on the SBA-15 surface.

As shown in FIG. 12, SBA-15 exhibited a typical type IV isotherm pattern with sharp capillary condensation with a H1 hysteresis loop at higher relative pressures. This is related to the 2-D hexagonal symmetry of the porous material. TEMPO-SBA-15 showed an adsorption-desorption isotherm curve similar to SBA-15 and a hysteresis loop. Both TEMPO-SBA-15 and SBA-15 exhibited narrow pore size distributions (12 inches). This shows the structural consistency of the catalyst before and after immobilization. SBA-15 exhibited very high surface area (883 m ² / g), and large pore volume (Table 3). A gradual decrease in surface area and pore volume following PTES-TEMPO immobilization indicates that the SBA-15 was successfully immobilized on the forerun channel. Fusion of TEMPO to the SBA-15 surface did not reduce the average pore size and the porous structure of the support was retained after functionalization.

Property analysis of TEMPO-SBA-15 catalyst and SBA-15 Sample Surface area (m ² / g) ^a Pore volume (cm ³ / g) ^b Pore size (nm) ^c TEMPO content (mmol / g) ^d SBA-15 883 1.24 5.6 - TEMPO-SBA-15 526 0.72 5.5 0.3

Calculated according to ^a BET equation

^b Single point forearm volume calculated at a relative pressure of 0.99 P / P ^o

^c Adsorption average pore diameter < RTI ID = 0.0 >

Heterogeneous catalysts (TEMPO-SBA-15) The thermal stability and the successful functionalization of TEMPO fused to the SBA-15 surface were analyzed by TGA curves (see FIG. 13). The first weight loss (<2%) of SBA-15 and TEMPO-SBA-15 was observed below 100 ℃. This is due to the evaporation of surface-adsorbed water. Thereafter, at 110 ° C to 235 ° C, a weight loss of 8.58% was observed at TEMPO-SBA-15 and a sharp decrease was observed at around 156 ° C. This is due to the decomposition of the 3- (4-oxy-TEMPO) propyl chain bound to the SBA-15 surface. This result represents a loss of 0.4 mmol of 3- (4-oxy-TEMPO) propyl per gram of catalytic material. From this, a loading of 0.3 mmol / g of TEMPO was estimated. In the absence of functionalized groups on the surface of the support, no weight loss was observed over the same temperature range. SBA-15 showed a total weight loss of only 3.21%. This is due to the condensation of the surface silanol which forms siloxane groups at higher temperatures (> 600 ° C) and releases water. For TEMPO-SBA-15, a weight loss of 16.68% between 235 and 1000 ° C is related to the consumption of unreacted ethoxy groups in the organosilane and also to partial silanol condensation. Elemental analysis confirmed the content of TEMPO in TEMPO-SBA-15 to be 0.3 mmol / g (see Table 3). This is what strongly supports the TGA results.

The successful immobilization of TEMPO on the SBA-15 surface was confirmed by FT-IR spectra (see FIG. 13). The IR spectra of PTES-TEMPO showed characteristic absorption bands at 1373 and 1165 cm ^-1 for CN and CO stretch vibrations, respectively. The spectra also showed peaks in the range of 2995-2870 cm ^-1 with respect to the CH stretch vibration. The characteristic bands of the silica framework were observed in both TEMPO-SBA-15 and SBA-15 (H-bonded silanol groups, 3600-3200 cm ^-1 ; asymmetric and symmetric Si-O -Si stretching, 1085 and 806 cm ^-1 ; Si-O stretching, 964 cm ^-1 ). The absorption peak at 1629 cm ^-1 is related to the bending vibration of the adsorbed water. In a heterogeneous catalyst (TEMPO-SBA-15), CN stretch vibration was confirmed at 1377 cm ^-1 . This indicates the presence of a TEMPO moiety. 1 of the OH stretching and bending (each of 3600-3200 cm ^-1 and 1629cm ^-1) and (2) Si-O stretching peak intensity decreases additional Si-O-Si stretching according to the (964 cm ^-1) The wide band indicates that PTES-TEMPO was successfully silanized on the SBA-15 surface (even though it overlaps with CO stretching).

Experimental Example 10: Morphological Analysis

The morphologies of TEMPO-SBA-15 and SBA-15 were analyzed by SEM and SEM. The results are shown in Fig. 15 ((a) SBA-15, (b) TEMPO-SBA-15). Both are composed of stick-shaped and bean-shaped particles of approximately 800-1000 nm in length. The FE-SEM images of TEMPO-SBA-15 and SBA-15 showed a well-aligned arrangement of porous channels of SBA-15 and an intact morphology after TEMPO immobilization (Fig. 15 (c) d) TEMPO-SBA-15)

Experimental Example 11: Analysis of yield of 2,5-DFF according to presence or absence of oxygen

The reaction conditions were 5-HMF (0.5 mmol), BAIB (0.75 mmol), ethyl acetate (solvent), RT and 1 h. The yield of 2,5-DFF was analyzed according to the presence or absence of oxygen. . At this time, the yield was controlled while controlling the amount of TEMPO.

In the case of a homogeneous TEMPO system that performs a 5-HMF oxidation reaction using a TEMPO catalyst under an oxygen-free system, a maximum yield of 57% was observed at a TEMPO loading of 0.1 mmol. In the case of using homogeneous TEMPO under an oxygen-rich system, the overall yield of TEMPO was high (see FIG. 16). Considering these results, it is considered that the oxygen molecule performs a function similar to BAIB by oxidizing the hydroxyamine form of the TEMPO catalyst to the radical form. A homogeneous TEMPO system rich in oxygen showed a high 2,5-DFF yield, but a small amount of 2,5-FDCA (2,5-furandicarboxylic acid) and 5-HMF peroxide was also observed (see FIG.

In the case of applying a heterogeneous TEMPO system (see the reaction scheme below) in which the 5-HMF oxidation reaction is carried out using oxygen-enriched TEMPO-SBA-15 catalyst (see the reaction scheme below), the peak of 2,5-DFF at 0.075 mmol of TEMPO The yield was 52%. 2,5-FDCA (2,5-furandicarboxylic acid) was not detected (see Fig. 18). Unlike the homogeneous system, the 2,5-furandicarboxylic acid was not detected Can be confirmed to be improved. This indicates that TEMPO moieties immobilized within the porous channels of SBA-15 play an important role. These results also indicate that SBA-15 plays an important role as a TEMPO support. A well-ordered uniform porous structure of SBA-15 can form a uniform active site of the TEMPO catalyst and control the spatial effect. These factors can affect the product selectivity because of the very important role of diffusion transport of the reactants to the active sites and diffusion of the products from the active sites.

[Reaction Scheme]

Experimental Example 12: Analysis of yield of 2,5-DFF according to co-catalyst type

The yield of 2,5-DFF according to the type of cocatalyst was analyzed under a heterogeneous TEMPO system in which a 5-HMF oxidation reaction was performed using a TEMPO-SBA-15 catalyst, and the results are shown in FIG. The reaction conditions consist of 5-HMF (0.5 mmol), TEMPO-SBA-15 (0.075 mmol), the secondary catalyst (Co-oxidants, 0.75 mmol) , ethyl acetate (solvent), RT, and the reaction time 1 h, O ₂ atmosphere Respectively. BAIB, a metal-based co-catalyst, hydrogen peroxide (35% aqueous H ₂ O ₂ ) and nitric acid (HNO ₃ ) were used as co-catalysts. As shown in Fig. 19, BAIB exhibited the highest 2,5-DFF yield of 52%. This is because under mild reaction conditions, some of the catalyst is inactivated and some of the catalyst decomposes 5-HMF.

Experimental Example 13: Analysis of 2,5-DFF yield according to reaction temperature

The yield of 2,5-DFF according to the reaction temperature was analyzed under a heterogeneous TEMPO system in which a 5-HMF oxidation reaction was performed using a TEMPO-SBA-15 catalyst, and the results are shown in FIG. The reaction conditions consisted of 5-HMF (0.5 mmol), TEMPO-SBA-15 (0.075 mmol TEMPO), BAIB (0.75 mmol), ethyl acetate (solvent) and O ₂ atmosphere.

Under a heterogeneous TEMPO system that performs 5-HMF oxidation using TEMPO-SBA-15 catalyst, the diffusion transfer of the reaction components can be reduced and the kinetic mobility of the reaction components can be increased by heating the reaction system And can improve the contact frequency with the TEMPO-SBA-15 catalyst. These effects are evident from the following experimental results. 20, the yield of 2,5-DFF was improved from 54% (room temperature) to 63% (reaction time was 60 minutes) when the temperature was increased to 40 ° C, . The production rate of 2,5-DFF tended to increase with increasing reaction temperature, but it was confirmed that the production rate of 2,5-DFF decreased after a certain time of reaction time at all temperatures. This is because 2,5-DFF has been degraded to other compounds that are not detected. At 50 ° C, the maximum yield of 2,5-DFF reached 57% within 30-45 min of reaction time, but the yield then decreased. This is due to the fact that 2,5-DFF decomposition occurred with increasing temperature.

Under a heterogeneous TEMPO system that performs a 5-HMF oxidation reaction using a TEMPO-SBA-15 catalyst, the adiabatic effect of SBA-15 combined with TEMPO can be beneficial. This is because TEMPO-SBA-15 can operate more efficiently over a wide temperature range. As a result of the above analysis, it was judged that it is most appropriate to react at 40 DEG C for 60 minutes in order to improve the yield of 2,5-DFF and to minimize the decomposition of the reaction components (see FIG. 20).

Experimental Example 14: Analysis of 2,5-DFF yield by acetic acid addition

The yield of 2,5-DFF following acetic acid addition was analyzed and the results are shown in FIG. All were tested under a homogeneous TEMPO system to perform a 5-HMF oxidation reaction using a heterogeneous TEMPO system to perform a 5-HMF oxidation reaction using a TEMPO-SBA-15 catalyst and a TEMPO catalyst. The reaction conditions consisted of 5-HMF (0.5 mmol), TEMPO (0.075 mmol), BAIB (0.75 mmol), AcOH (0.05 mmol, if used), ethyl acetate (solvent), O ₂ atmosphere and reaction time 1 h. As shown in FIG. 21, it can be seen that addition of a small amount of acetic acid (0.05 mol) remarkably increases the yield (heterogeneous TEMPO system: 73%, homogeneous TEMPO system: 78%). The heterogeneous TEMPO system that performs the 5-HMF oxidation reaction using the TEMPO-SBA-15 catalyst and the homogeneous TEMPO system that performs the 5-HMF oxidation reaction using the TEMPO catalyst. Showed almost similar results. This demonstrates the advantage of using SBA-15 as a material supporting TEMPO. The catalyst support SBA-15 may have minimal effect on TEMPO since the active sites are uniformly distributed in the porous structure. In addition, suitable organosilane linkers (CPTES) can provide sufficient space to help TEMPO moieties with a profile chain react to reduce steric hindrance in the environment. Taking these results into account, the TEMPO-SBA-15 catalyst will behave similarly to a catalyst in a homogeneous TEMPO system that performs a 5-HMF oxidation reaction using a TEMPO catalyst.

Experimental Example 15: Stability and Recycling Test of TEMPO-SBA-15

The results of testing the stability of TEMPO-SBA-15 by repeatedly using TEMPO-SBA-15 under the same reaction conditions are shown in Figures 22-24. The reaction conditions are 5-HMF (0.5 mmol), TEMPO-SBA-15 (0.075 mmol TEMPO), BAIB (0.75 mmol), AcOH (0.05 mmol), ethyl acetate (solvent), O ₂ atmosphere, reaction temperature 40 ℃, reaction Time 1h. As shown in Fig. 22, the yield of 2,5-DFF was maintained at 71% or more in each cycle. After five consecutive experiments, TEMPO-SBA-15 showed no chemically and structurally deteriorated form (see FIGS. 23 and 24).

Experimental Example 16: One-Pot Conversion from fructose to 2,5-DFF [

It is more desirable to synthesize 2,5-DFF directly from 5-HMF by directly synthesizing 2,5-DFF from a hexose such as fructose. This is because it is possible to avoid the separation and purification of intermediates and save energy, time, and solvent. The yield of 2,5-DFF by one-port reaction from fructose to 2,5-DFF was analyzed and the results are shown in Figures 25 and 26. The one-port reaction was carried out with three different solvents. The reaction conditions were fructose (0.5 mmol), NbCl5 (0.1 mmol), solvent, reaction temperature 80 ° C, reaction time 30 min. The reaction was carried out using DMSO (Dimethylsulfoxide), DMA (N, N-Dimethylacetamide) and DMF (N, N-Dimethylformamide) as solvents. As shown in FIG. 25, the overall yield of 5-HMF was high. After cooling to room temperature, TEMPO-SBA-15 was added to the obtained 5-HMF and purged with oxygen molecules. The reaction conditions were TEMPO-SBA-15 (0.075 mmol), BAIB (0.75 mmol) solvent, oxygen atmosphere, reaction temperature 25 ℃, reaction time 1 hour. The yield of 2,5-DFF thus produced is shown in Fig. The yield of 2,5-DFF was calculated based on the 5-HMF produced in the one-port reaction. In all groups tested, yields were 45% or greater (see FIG. 26). This indicates that the TEMPO-SBA-15 catalyst is applicable to various fields. These results are indicative of the industrial scale-up possibilities of the 2,5-DFF synthesis process.

The resulting 2,5-DFF can be optionally isolated from the reaction mixture by any known means. For example, there may be mentioned a liquid-liquid extraction method, a vacuum distillation / sublimation method of 2,5-DFF, a method of diluting with water, and extraction with a suitable organic solvent such as dichloromethane.

After isolation, the 2,5-DFF can be purified by any known means. For example, vacuum sublimation, filtration through silica in dichloromethane, recrystallization, and soxhlet extraction.

While the present invention has been particularly shown and described with reference to exemplary embodiments thereof, it is to be understood that the invention is not limited to the disclosed embodiments, but, on the contrary, This is possible.

Claims (30)

And 5-hydroxymethyl furfural is oxidized in a low-boiling solvent using a metal-free catalyst and a cocatalyst.
The method according to claim 1,
Wherein the metal-free catalyst is a nitroxyl radical.
The method according to claim 1,
Wherein the metal-free catalyst is 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl.
The method according to claim 1,
Wherein the co-catalyst is bis (acetoxy) iodobenzene, acetic acid or a mixture thereof.
The method according to claim 1,
The 5-hydroxymethyl furfural, non-metal catalyst,
Wherein the molar ratio of 5-hydroxymethyl furfural: metal-free catalyst: cocatalyst is 1: 0.05 to 1: 0.2 to 2.
The method according to claim 1,
Wherein the low boiling point solvent comprises at least one selected from the group consisting of ethyl acetate, dichloromethane, acetonitrile, diethyl ether, water and toluene.
The method according to claim 1,
Wherein the oxidation reaction step is performed for 5 minutes to 120 minutes.
The method according to claim 1,
Wherein the oxidation reaction step is performed at a temperature of from 30 캜 to 75 캜.
The method according to claim 1,
Wherein the reaction is carried out in an oxygen atmosphere.
A process for producing 2,5-diformylfuran comprising the step of subjecting 5-hydroxymethyl furfural to an oxidation reaction in a low-boiling solvent using a porous nonmetal catalyst and a co-catalyst.
The method of claim 10,
Wherein the porous metal-free catalyst is supported on a porous solid support with a silica nitroxyl radical.
The method of claim 11,
Wherein the porous solid support is porous silica.
The method of claim 10,
The porous metal-free catalyst is composed of a structure in which 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl is immobilized on porous silica,
Wherein the immobilization is performed through an organosilane linker. &Lt; RTI ID = 0.0 &gt; 25. &lt; / RTI &gt;
The method of claim 10,
The porous metal-
Reacting 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl with 3- (chloro) propyltriethoxysilane to give 3- (4-oxy- -Tetramethylpiperidine-1-oxyl) propyl-propoxysilane; And
Silanization of the porous silica using the 3- (4-oxy-2,2,6,6-tetramethylpiperidine-1-oxyl) propyl-propoxysilane prepared in the above step &Lt; / RTI &gt;
The method of claim 10,
Wherein the co-catalyst is bis (acetoxy) iodobenzene, acetic acid or a mixture thereof.
The method of claim 10,
The 5-hydroxymethyl furfural, porous, metal-free catalyst and co-
Wherein the molar ratio of 5-hydroxymethyl furfural: porous non-metal catalyst: co-catalyst is 0.5: 0.018 to 1: 0.75 to 0.8.
The method of claim 10,
Wherein the low boiling point solvent comprises at least one selected from the group consisting of ethyl acetate, dichloromethane, acetonitrile, diethyl ether, water and toluene.
The method of claim 10,
Wherein the oxidation reaction step is performed for 5 minutes to 120 minutes.
The method of claim 10,
Wherein the oxidation reaction step is performed at a temperature of from 30 캜 to 75 캜.
The method of claim 10,
Wherein the reaction is carried out in an oxygen atmosphere.
5-hydroxymethyl furfural is produced by oxidation reaction in a low-boiling solvent using a metal-free catalyst and a cocatalyst.
23. The method of claim 21,
Wherein the metal-free catalyst is 4-hydroxy-2,2,6,6, -tetramethylpiperidine-1-oxyl,
Wherein the co-catalyst is bis (acetoxy) iodobenzene or acetic acid or a mixture thereof,
The metal-free catalyst and the auxiliary catalyst are used in a molar ratio of 0.05 to 1: 0.2 to 2 mol based on the molar amount of the 5-hydroxymethyl furfural used in the oxidation reaction,
Wherein the solvent comprises at least one member selected from the group consisting of ethyl acetate, dichloromethane, acetonitrile, diethyl ether, water and toluene.
5-hydroxymethyl furfural is produced by oxidation reaction in a low-boiling solvent using a porous non-metal catalyst and a co-catalyst.
24. The method of claim 23,
The porous metal-free catalyst is composed of a structure in which 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl is immobilized on porous silica,
Wherein the immobilization is performed through an organosilane linker,
Wherein the co-catalyst is bis (acetoxy) iodobenzene or acetic acid or a mixture thereof,
The 5-hydroxymethyl furfural, porous, metal-free catalyst and co-
The molar ratio of 5-hydroxymethyl furfural: porous non-metal catalyst: co-catalyst is 0.5: 0.018 to 1: 0.75 to 0.8,
Wherein the low boiling point solvent comprises at least one selected from the group consisting of ethyl acetate, dichloromethane, acetonitrile, diethyl ether, water and toluene.
24. The method of claim 23,
The porous metal-
Reacting 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl with 3- (chloro) propyltriethoxysilane to give 3- (4-oxy- -Tetramethylpiperidine-1-oxyl) propyl-propoxysilane; And
Silanization of the porous silica using the 3- (4-oxy-2,2,6,6-tetramethylpiperidine-1-oxyl) propyl-propoxysilane prepared in the above step Lt; RTI ID = 0.0 &gt; of 2,5-diformylfuran. &Lt; / RTI &gt;
A process for producing a porous metal-free catalyst used for producing 2,5-diformylfuran,
Reacting a product obtained by reacting 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl and an organosilane with porous silica to silanate the porous silica, &Lt; / RTI &gt;
27. The method of claim 26,
Wherein the organosilane is 3- (chloro) propyl triethoxysilane.
A process for producing a porous metal-free catalyst used for producing 2,5-diformylfuran,
Reacting 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl with 3- (chloro) propyltriethoxysilane to give 3- (4-oxy- -Tetramethylpiperidine-1-oxyl) propyl-propoxysilane; And
Reacting the 3- (4-oxy-2,2,6,6-tetramethylpiperidine-1-oxyl) propyl-free-ethoxysilane prepared in the above step with porous silica to silane the porous silica By weight based on the total weight of the catalyst.
A porous, metal-free catalyst prepared according to any one of claims 26 to 28 and used in the preparation of 2,5-diformylfuran,
Comprising a structure in which 4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl is immobilized on porous silica,
Wherein the immobilization is carried out through an organosilane linker.
29. The method of claim 29,
Wherein said organosilane is 3- (chloro) propyltriethoxysilane.

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