Method for preparing 5-formyl furoic acid

Abstract

The invention provides a method for preparing 5-formyl furoic acid, and relates to the technical field of biological platform compounds. According to the method for preparing the 5-formyl furoic acid, a solution composed of substrates HMF, TEMPO, acid, salt and a solvent is subjected to an oxidation reaction under oxidizing gas, and the 5-formyl furoic acid is obtained. The salt is selected from nitrite and / or nitrate. According to the method, the HMF conversion rate is high, and the FFCA selectivity is high.

Description

Technical Field

[0001] This invention belongs to the field of biological platform compound technology and relates to a method for preparing 5-formylfuronic acid. Background Technology

[0002] 5-Hydroxymethylfurfural (HMF) is a fundamental biological platform compound that can be converted into 2,5-furandicarboxaldehyde (DFF), 5-hydroxymethyl-2-furancarboxylic acid (HMFCA), 5-formylfuronic acid (FFCA), and 2,5-furandicarboxylic acid (FDCA), among others. FFCA is an important biomaterial with broad application prospects in pharmaceuticals, chemical intermediate synthesis, and furan-furan-based polyesters. The oxidation of HMF to FFCA typically employs noble metal catalysts or supported noble metal catalysts, but often suffers from problems such as high reaction temperatures and high oxygen pressures, hindering the industrial-scale production of FFCA.

[0003] Therefore, the industry urgently needs to develop a method for preparing FFCA with lower cost and milder conditions. Summary of the Invention

[0004] To address the aforementioned technical problems, this invention provides a method for preparing 5-formylfuronic acid.

[0005] The technical solution of the present invention is as follows: A method for preparing 5-formylfuronic acid involves an oxidation reaction of a solution consisting of a substrate HMF, TEMPO, an acid, a salt, and a solvent under an oxidizing gas. The salt is selected from nitrites and / or nitrates.

[0006] Preferably, the concentration of the substrate HMF in the solution is 5-20 wt%; The solvent is selected from one or a combination of two or more of 1,2-dichloroethane, 1,1-dichloroethane, trichloroethane, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, and xylene. Preferably, the molar ratio of TEMPO to the substrate HMF is 1-15:100.

[0007] Preferably, the acid is selected from inorganic medium-strong acids and / or inorganic strong acids, and the weight of the acid is 10-30% of the weight of the substrate HMF.

[0008] More preferably, the acid is selected from one or a combination of two or more of the following: hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, and sulfuric acid.

[0009] Preferably, the nitrite is selected from alkali metal nitrites, and the nitrate is selected from alkali metal nitrates.

[0010] Preferably, the molar ratio of the salt to the substrate HMF is 5-15:100.

[0011] Preferably, the oxidizing gas is selected from oxygen and / or air, and the pressure is 0.08-0.6 MPa.

[0012] Preferably, the oxidation reaction is carried out at a temperature of 10-60°C for a time of 16-32 hours.

[0013] Preferably, the oxidation reaction is followed by post-treatment: removing the solvent and then purifying by column chromatography.

[0014] The beneficial effects of this invention are as follows: This invention uses HMF as a raw material, an oxidizing gas as the main oxidant, TEMPO as a co-oxidant to improve oxidation selectivity and reduce oxidation activation energy, and salt as an auxiliary agent, achieving highly efficient conversion of HMF and highly selective conversion of FFCA under acidic conditions. The reaction conditions are relatively mild, avoiding the use of expensive noble metal catalysts. Attached Figure Description

[0015] Figure 1 This is the HPLC chromatogram of FFCA standard.

[0016] Figure 2 The image shows the HPLC chromatogram of high-purity FFCA obtained in Example 1. Detailed Implementation

[0017] The technical solution of the present invention will be further explained and described below through specific embodiments.

[0018] This invention proposes a method for preparing 5-formylfuronic acid, which is obtained by oxidizing a solution composed of substrate HMF, TEMPO, acid, salt and solvent under an oxidizing gas. The salt is selected from nitrites and / or nitrates.

[0019] HMF, in its furan structure, contains one hydroxymethyl group and one aldehyde group. The conversion of HMF to FFCA requires the hydroxymethyl group to be oxidized to a carboxyl group, while the aldehyde group remains unoxidized. Therefore, the oxidation reaction needs to have high selectivity and operate under relatively mild conditions; otherwise, the aldehyde group is easily oxidized. This invention uses an oxidizing gas as the primary oxidant, TEMPO as a co-oxidant to improve oxidation selectivity and lower the activation energy, and a salt as a co-catalyst to further improve oxidation selectivity and lower the activation energy. The acid can combine with TEMPO and the salt to promote catalytic oxidation and improve oxidation efficiency. Therefore, this invention synergistically utilizes the primary oxidant, co-oxidant, co-catalyst, and acid to form a suitable "oxidation-catalysis" system, which can fully oxidize HMF under relatively mild conditions and also improve the selectivity of FFCA.

[0020] In some embodiments, the concentration of the substrate HMF in the solution is 5-20 wt%; The solvent is selected from one or a combination of two or more of 1,2-dichloroethane, 1,1-dichloroethane, trichloroethane, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, and xylene. In some embodiments, the molar ratio of TEMPO to substrate HMF is 1-15:100. For example, the molar ratio of TEMPO to substrate HMF can be any value or any value in between, such as 1:100, 3:100, 5:100, 6:100, 8:100, 10:100, 12:100, 15:100, etc., without any particular limitation.

[0021] In some embodiments, the acid is selected from inorganic moderately strong acids and / or inorganic strong acids, and the weight of the acid is 10-30% of the weight of the substrate HMF. For example, the weight of the acid is any value or any value between 10%, 15%, 20%, 25%, 30% of the weight of the substrate HMF, without particular limitation.

[0022] In some embodiments, the acid is selected from one or a combination of two or more of the following: hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, and sulfuric acid. The hydrochloric acid may be concentrated hydrochloric acid, and the sulfuric acid concentration may be 30-85 wt%.

[0023] In some embodiments, the nitrite is selected from alkali metal nitrites, and the nitrate is selected from alkali metal nitrates.

[0024] In some embodiments, the molar ratio of salt to substrate HMF is 5-15:100. For example, the molar ratio of salt to substrate HMF can be any value or any value in between, such as 5:100, 7:100, 10:100, 12:100, 15:100, etc., without any particular limitation.

[0025] In some embodiments, the oxidizing gas is selected from oxygen and / or air, and the pressure is 0.08-0.6 MPa. For example, the pressure of the oxidizing gas can be any value or any value between 0.08 MPa, 0.1 MPa, 0.15 MPa, 0.2 MPa, 0.25 MPa, 0.3 MPa, 0.35 MPa, 0.4 MPa, 0.55 MPa, 0.5 MPa, etc., without particular limitation. Further, the pressure of the oxidizing gas can be 0.1-0.2 MPa.

[0026] In some embodiments, the oxidation reaction is carried out at a temperature of 10-60°C for a time of 16-32 hours. For example, the oxidation reaction temperature can be 10°C, 15°C, 20°C, 25°C, 30°C, 35°C, 40°C, 45°C, 50°C, 55°C, 60°C, etc., and the time can be 16 hours, 20 hours, 24 hours, 28 hours, 32 hours, etc.

[0027] The oxidation reaction of this invention has high reactivity and can be carried out under relatively mild conditions, with the pressure of the oxidizing gas being atmospheric or close to atmospheric pressure, and the reaction temperature being room temperature or slightly above room temperature.

[0028] In some embodiments, the oxidation reaction includes post-treatment: solvent removal followed by purification by column chromatography. The reaction system after the oxidation reaction contains various components, such as the product FFCA, byproducts, TEMPO, salts, and acids, and a portion of the FFCA product may also be precipitated, making solid-liquid separation impossible. Solvent removal (e.g., by rotary evaporation) followed by column chromatography can yield FFCA with higher purity. The column chromatography method involves elution and purification in a silica gel column using petroleum ether:ethyl acetate = 4:1 (volume ratio) as the eluent.

[0029] The technical solution of the present invention will be further described and illustrated below with reference to various embodiments. Unless otherwise specified, the parts mentioned in the following embodiments are parts by weight.

[0030] Example 1 At 25℃, 1.26 g (10 mmol) HMF, 0.156 g (1 mmol) TEMPO, 0.069 g (1 mmol) sodium nitrite, and 16 mL dichloromethane were placed in a reaction flask and stirred until dissolved. Then, 0.257 g of 30 wt% hydrochloric acid was added. After purging the air from the reaction flask, an oxygen bulb was connected (pressure 0.1 MPa), and the reaction was stirred for 30 h. Samples were taken, and high-performance liquid chromatography (HPLC) was used for detection. The standard was characterized using an external standard curve method, and the HMF conversion was found to be 100%, with a selectivity of 79% for FFCA. The oxidation reaction product was subjected to rotary evaporation to remove the solvent, yielding a crude product. The crude product was purified by column chromatography to obtain a pale yellow solid FFCA.

[0031] The HPLC detection method was as follows: The sample to be tested was dissolved in ultrapure water, sonicated for 5 min, then shaken for 1 min, and sonicated again for 5 min to ensure complete dissolution. The solution was then diluted to volume with a volumetric flask to obtain a stock solution with a concentration of 1 g / L. Then, 1 g of the stock solution was diluted 10 times with ultrapure water to obtain the test solution. The test solution was drawn using a suitable syringe, and a 0.22 μm PES needle filter was securely connected to the syringe outlet. The syringe plunger was slowly pushed to allow the sample to pass through the filter head and be collected in an LC vial. An Agilent HPLC (2695) was used for detection, equipped with an HPX-87H column (column temperature: 60℃) and a UV-Vis detector. The mobile phase for the HPLC was 0.005 M H₂SO₄ aqueous solution (0.6 mL / min). The product was analyzed at its maximum absorption wavelength (λ = 285 nm). Quantitative analysis of FFCA was based on an external standard method.

[0032] Example 2 The difference between this embodiment and Example 1 is that in Example 1, dichloromethane was replaced with an equal volume of 1,2-dichloroethane. All other steps remained unchanged. The HMF conversion was measured to be 100%, and the selectivity for FFCA was 83%.

[0033] Example 3 The difference between this embodiment and Example 1 is that in Example 1, concentrated hydrochloric acid was replaced with an equal weight of 50wt% sulfuric acid. The remaining steps remained unchanged. The HMF conversion rate was measured to be 100%, and the selectivity for FFCA was 68%.

[0034] Example 4 The difference between this embodiment and Example 1 is that in Example 1, sodium nitrite was replaced with an equimolar amount of sodium nitrate. All other steps remained unchanged. The HMF conversion was measured to be 100%, and the selectivity for FFCA was 59%.

[0035] Examples 5-11 and Comparative Examples 1-3 Examples 5-11 and Comparative Examples 1-3 were based on Example 1, with adjustments made to the amounts of reactants, while the remaining steps remained unchanged. The results are shown in Table 1 below.

[0036] Table 1

[0037] Example 12 1.26 g (10 mmol) HMF, 0.156 g (1 mmol) TEMPO, 0.069 g (1 mmol) sodium nitrite, and 10 mL chloroform were placed in a reaction flask at 25 °C and stirred until dissolved. Then, 0.2 g of 30 wt% hydrochloric acid was added, and after purging the air from the flask, an oxygen bulb was connected (pressure 0.1 MPa). The reaction was stirred for 30 h. After the reaction was complete, sodium carbonate was added for neutralization. Solid-liquid separation was performed by filtration, and the filtrate was analyzed by high-performance liquid chromatography (HPLC). The standard was characterized using an external standard curve method. The HMF conversion was found to be 100%, and the selectivity for FFCA was 75%. The solvent was removed from the filtrate by vacuum distillation to obtain the crude product. The crude product was purified by column chromatography to obtain a pale yellow solid FFCA.

[0038] Example 13 The difference between this embodiment and Embodiment 12 is that in Embodiment 12, the reaction temperature was adjusted from 25°C to 50°C. All other steps remained unchanged. The HMF conversion rate was measured to be 100%, and the selectivity for FFCA was 77%.

[0039] Example 14 The difference between this embodiment and Embodiment 12 is that in Embodiment 12, the reaction time was adjusted from 30 hours to 20 hours. All other steps remained unchanged. The HMF conversion rate was measured to be 100%, and the selectivity for FFCA was 56%.

[0040] Example 15 The difference between this embodiment and Embodiment 12 is that in Embodiment 12, the oxygen pressure was adjusted from 0.1 MPa to 0.2 MPa. The remaining steps remained unchanged. The HMF conversion rate was measured to be 100%, and the selectivity for FFCA was 85%.

[0041] Example 16 The difference between this embodiment and Embodiment 15 is that in Embodiment 15, oxygen was replaced with air at the same pressure. All other steps remained unchanged. The HMF conversion rate was measured to be 100%, and the selectivity for FFCA was 82%.

[0042] Example 17 The difference between this embodiment and Embodiment 12 is that in Embodiment 12, 0.2g of 30wt% hydrochloric acid was replaced with 0.2g of 20wt% hydrochloric acid. All other steps remained unchanged. The HMF conversion rate was measured to be 100%, and the selectivity for FFCA was 71%.

[0043] Example 18 The difference between this embodiment and Embodiment 12 is that in Embodiment 12, 0.2g of 30% hydrochloric acid was replaced with 0.3g of 30wt% sulfuric acid. The remaining steps remained unchanged. The HMF conversion rate was measured to be 100%, and the selectivity for FFCA was 72%.

[0044] As described above, the basic principles, main features, and advantages of the present invention have been shown and described. Those skilled in the art should understand that the present invention is not limited to the above embodiments, which are merely preferred embodiments and should not be construed as limiting the scope of the invention. All equivalent changes and modifications made in accordance with the scope of the patent and the description should still fall within the scope of the present invention. The scope of protection of this invention is defined by the appended claims and their equivalents.

Claims

1. A method for preparing 5-formylfuronic acid, characterized in that, The solution consisting of substrate HMF, TEMPO, acid, salt, and solvent is oxidized under an oxidizing gas to obtain the product. The salt is selected from nitrites and / or nitrates.

2. The method for preparing 5-formylfuronic acid according to claim 1, characterized in that, The concentration of the substrate HMF in the solution is 5-20 wt%; The solvent is selected from one or a combination of two or more of 1,2-dichloroethane, 1,1-dichloroethane, trichloroethane, dichloromethane, chloroform, ethyl acetate, acetonitrile, toluene, and xylene.

3. The method for preparing 5-formylfuronic acid according to claim 1, characterized in that, The molar ratio of TEMPO to the substrate HMF is 1-15:

100.

4. The method for preparing 5-formylfuronic acid according to claim 1, characterized in that, The acid is selected from inorganic medium-strong acids and / or inorganic strong acids, and the weight of the acid is 10-30% of the weight of the substrate HMF.

5. The method for preparing 5-formylfuronic acid according to claim 4, characterized in that, The acid is selected from one or a combination of two or more of the following: hydrochloric acid, hydrobromic acid, hydroiodic acid, phosphoric acid, and sulfuric acid.

6. The method for preparing 5-formylfuronic acid according to claim 1, characterized in that, The nitrite is selected from alkali metal nitrites, and the nitrate is selected from alkali metal nitrates.

7. The method for preparing 5-formylfuronic acid according to claim 1, characterized in that, The molar ratio of the salt to the substrate HMF is 5-15:

100.

8. The method for preparing 5-formylfuronic acid according to claim 1, characterized in that, The oxidizing gas is selected from oxygen and / or air, and the pressure is 0.08-0.6 MPa.

9. The method for preparing 5-formylfuronic acid according to claim 1, characterized in that, The oxidation reaction is carried out at a temperature of 10-60℃ for a time of 16-32 hours.

10. The method for preparing 5-formylfuronic acid according to claim 1, characterized in that, The oxidation reaction is followed by post-processing: removal of the solvent and purification by column chromatography.

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