JP2023102520A - Method for producing furandicarboxylic acid - Google Patents

Abstract

To provide a method for producing FDCA which generates FDCA with less environmental load and less input energy under simpler conditions and achieves oxidation of a furan compound to the isolation of FDCA in a series of steps.SOLUTION: A method for producing FDCA according to one embodiment comprises a mixing step, an oxidation step and a separation step. The mixing step mixes a furan compound, a TEMPO analog, sodium bicarbonate and an oxidizing agent with water at 50°C or less to produce a reaction solution. The oxidation step stirs the reaction solution at a reaction temperature of 0 to 50°C and for a reaction time of 0.5 to 24 hours to oxidize the furan compound and produce FDCA. After the oxidation step, a reducing agent for reducing the oxidizing agent is added to stop the oxidation step. The separation step adds an acid to the reaction solution to acidify the reaction solution and precipitates FDCA which is dissolved in the reaction solution.SELECTED DRAWING: Figure 1

Description

The present invention relates to a method for producing furandicarboxylic acid.

Furandicarboxylic acid (FDCA: Furan-2,5-DiCarboxylic Acid) is being studied as a raw material for bioplastics. FDCA is produced by oxidizing a furan compound such as hydroxymethylfurfural (5-HMF: 5-HydroxyMethyl-2-Furaldehyade), which is a biologically derived compound, as a raw material.

Conventionally, FDCA generally oxidizes, for example, 5-HMF using oxygen in the air with a heavy metal as a catalyst. However, heavy metal catalysts are not only expensive, but also have a great impact on the environment and the human body. Therefore, it has been proposed to oxidize FDCA using an organic catalyst such as TEMPO (2,2,6,6-TetraMethylPiperidine-1-Oxyl) (see Patent Document 1).

However, Patent Document 1 assumes that a phase transfer catalyst is used in the presence of halides such as bromides and chlorides in two liquid phases, hydrophilic and hydrophobic. Moreover, in the case of Patent Document 1, the reaction in a highly alkaline environment with a pH exceeding 9 is required as the condition. Therefore, in the case of Patent Document 1, oxidation at a low temperature is required from the viewpoint of maintaining the stability of the phase transfer catalyst or avoiding hydrolysis of the hydrophobic solvent. As a result, there is a problem that the input energy is increased for cooling. Furthermore, in the case of Patent Literature 1, it is assumed that a hydrophobic organic solvent is used, which causes problems such as complication of equipment and a large load on the environment.

International publication WO2019/072920 specification

Therefore, it is an object of the present invention to provide a method for producing FDCA that produces FDCA under simpler conditions with less load on the environment and less input energy, and achieves from oxidation of furan compounds to isolation of FDCA in a series of steps.

In order to solve the above problems, this embodiment uses water as a solvent for the reaction solution. As a result, it is not necessary to use a hydrophobic solvent that is highly flammable and has a large burden on the environment. Also, the oxidation of furan compounds to FDCA can be performed at temperatures close to room temperature. Then, by adding an acid to the reaction solution containing the oxidized FDCA to create an acidic environment, the insoluble FDCA crystallizes and precipitates. Therefore, the FDCA produced is easily isolated without incurring complicated steps. Therefore, the load on the environment and input energy can be reduced, FDCA can be produced under simpler conditions, and a series of steps from oxidation of furan compounds to isolation of FDCA can be performed.

Schematic diagram showing steps of a method for manufacturing FDCA according to one embodiment Schematic diagram illustrating an example of a method for manufacturing FDCA according to one embodiment Schematic diagram illustrating an example of a method for manufacturing FDCA according to one embodiment Schematic diagram illustrating an example of a method for manufacturing FDCA according to one embodiment Schematic diagram illustrating an example of a method for manufacturing FDCA according to one embodiment Schematic diagram illustrating an example of a method for manufacturing FDCA according to one embodiment Schematic diagram illustrating an example of a method for manufacturing FDCA according to one embodiment Schematic diagram illustrating an example of a method for manufacturing FDCA according to one embodiment Schematic diagram illustrating an example of a method for manufacturing FDCA according to one embodiment Schematic diagram showing a comparative example of a method for manufacturing FDCA according to one embodiment

An embodiment of a method for manufacturing FDCA will be described below.
As shown in FIG. 1, the method for producing FDCA according to one embodiment includes a mixing step (S101), an oxidation step (S102), a termination step (S103) and a separation step (S104). These mixing, oxidation, termination and separation steps are performed as a series of steps.

(Mixing process)
The mixing step mixes a furan compound, a TEMPO analogue, sodium bicarbonate and an oxidizing agent with water as a solvent. TEMPO analogs are compounds represented by, for example, 2,2,6,6-tetramethylpiperidine-1-oxyl. In addition, TEMPO analogs include, for example, 2,2,6,6-tetramethylpiperidin-1-oxy-4-ol (TEMPOL), l-oxyl-2,2,6,6-tetramethylpiperidin-4-on (TEMPON), l-oxyl-2,2,6,6-tetramethyl-4-carboxyl-piperidine (4-carboxy-TEMPO), 1-oxyl-2,2,5,5-tetramethylpyrrolidine, 4-methoxy-2,2,6,6-tetramethylpiperidine-N-oxyl, 4-oxo-2,2,6,6-tetramethylpiperidine-N-oxyl, l-oxo-2,2,5,5-tetramethyl-3-carboxylpyrrolidine (3-carboxy-PROXYL), 4-benzoyloxy-2,2,6,6-tetramethylpiperidine-N-oxide and the like.

A typical furan compound is, for example, 5-HMF. The furan compound is not limited to 5-HMF, and intermediates such as 5-formyl-2-furancarboxylic acid (FFCA) and 2,5-furandaldehyde (FDAL) that ultimately produce FDCA by oxidation of functional groups can also be used. The oxidizing agent is hypochlorous acid or an aqueous solution of hypochlorite. The oxidizing agent may be hypochlorous acid or hypochlorite alone, or may be an aqueous solution of hypochlorous acid or an aqueous solution of hypochlorite. Although the more the oxidizing agent is used, the more the furan compound is oxidized, the more the oxidizing agent is used, the more likely it is that a side reaction will occur, which may lead to the formation of side reaction products and the decomposition of the formed FDCA. Therefore, when 5-HMF is used as the furan compound, the oxidizing agent is preferably added in an amount of 1 to 10 molar equivalents, more preferably 3 to 5 molar equivalents, relative to the furan compound. Moreover, it is preferable to change the molar equivalent of the oxidizing agent according to the furan compound as the starting material.

These sodium bicarbonate, TEMPO analogue, furan compound and oxidant are mixed with water. That is, the reaction liquid is an aqueous solution containing sodium hydrogen carbonate, a TEMPO analogue, a furan compound and an oxidizing agent in water.

In the mixing step, the reaction solution is mixed by stirring at a temperature close to room temperature. The mixing step may be performed at a temperature in the range of 0 to 50°C, more preferably in the range of 20 to 35°C, which is room temperature. Note that 0° C. in the mixing step is not strictly 0° C., but may be, for example, about 2 to 3° C., which is 10° C. or less that can be cooled with ice. Further, the reaction liquid containing the furan compound becomes weakly alkaline with a pH of less than 9.0 by adding sodium hydrogen carbonate.

In this embodiment, the mixing step is performed using either mixing method A or mixing method B.
(Mixing method A)
Mixing method A is used when the concentration of the raw material furan compound contained in the reaction solution is relatively low. Mixing method A is subdivided into a first mixing step and a second mixing step. Mixing method A mixes a furan compound, a TEMPO analog and sodium hydrogen carbonate with water in the first mixing step. In the second mixing step, an oxidizing agent is added to the aqueous solution mixed in the first mixing step. In this second mixing step, the oxidizing agent is added to the aqueous solution while stirring while maintaining the aqueous solution at 0-50°C. Thus, for mixing method A, an oxidizing agent is added to an aqueous solution containing a furan compound, a TEMPO analogue and sodium bicarbonate.

In the case of mixing method A, the concentration of the furan compound in the aqueous solution is 0.01 to 5% by mass. In particular, in the case of mixing method A, the concentration of the furan compound in the aqueous solution is preferably 0.1 to 1% by mass. Further, 0.1 to 300 mg of the TEMPO analog is added per 100 ml of the aqueous solution containing the furan compound. In particular, the TEMPO analog is preferably added in an amount of 1 to 40 mg per 100 ml of the aqueous solution. Furthermore, 0.1 to 30 g of sodium bicarbonate is added per 100 ml of the aqueous solution containing the furan compound. In particular, sodium hydrogen carbonate is preferably added in an amount of 1 to 10 g per 100 ml of the aqueous solution.

(Mixing method B)
Mixing method B is used when the concentration of the raw material furan compound contained in the reaction solution is relatively high. Mixing method B, like mixing method A, is subdivided into a first mixing step and a second mixing step. Mixing method B mixes a TEMPO analogue, sodium hydrogen carbonate and an oxidizing agent with water in the first mixing step. In the second mixing step, an aqueous solution of a furan compound is added to the aqueous solution mixed in the first mixing step. In this second mixing step, the aqueous solution of the furan compound is added with stirring while the aqueous solution produced in the first mixing step is maintained at 0 to 50°C. Thus, for mixing method B, the aqueous solution of the furan compound is added to the aqueous solution containing the TEMPO analogue, sodium bicarbonate and the oxidizing agent.

In the case of mixing method B, the concentration of the furan compound in the aqueous solution can be in the range of 0.1 to 95% by mass, preferably 5 to 95% by mass. In particular, in the case of mixing method B, it is more preferable that the concentration of the furan compound in the aqueous solution is 5 to 50% by mass. The TEMPO analog is added in an amount of 30-3500 mg per 100 ml of the aqueous solution containing the furan compound. 1 to 120 g of sodium bicarbonate is added per 100 ml of the aqueous solution containing the furan compound.

The reaction solution produced by mixing method A or mixing method B contains excess sodium hydrogen carbonate. Specifically, 2 to 20 equivalents of sodium bicarbonate are added to the furan compound as a raw material by adding the reaction solution in the above ratio. In this case, the reaction solution preferably contains 5 to 10 equivalents of sodium hydrogen carbonate with respect to the furan compound. In addition, the reaction liquid produced by mixing method A or mixing method B contains 0.01 to 1 equivalent of TEMPO with respect to the furan compound used as a raw material by adding in the above ratio. In this case, the reaction solution preferably contains 0.02 to 0.2 equivalents of TEMPO with respect to the furan compound.

(Oxidation process)
The oxidation step is a step of oxidizing the furan compound contained in the reaction liquid generated in the mixing step. The oxidizing agent is, for example, hypochlorous acid (HOCl) or sodium hypochlorite (NaOCl) as described above. The oxidizing agent is added in an amount of 1 to 10 molar equivalents relative to the furan compound contained in the reaction solution at the above ratio. In the oxidation step, the furan compound contained in the reaction solution is oxidized with an oxidizing agent using the TEMPO analogue as a catalyst. That is, in the oxidation step, a ketone group or a hydroxymethyl group contained as a functional group of the furan compound is oxidized to a carboxyl group. As a result, the furan compound is oxidized to FDCA.

In the oxidation step, the reaction temperature is set at 0-50°C. The reaction temperature is preferably set to room temperature of about 20 to 35°C. By setting the reaction temperature to a room temperature of 20 to 35° C., heating and cooling are not required in the oxidation step, and the input energy can be reduced. In the oxidation step, the reaction time is set to 0.5 to 24 hours. Thus, in the oxidation step, the reaction solution mixed in the mixing step is stirred at 0 to 50° C., preferably at room temperature for 0.5 to 24 hours. Thereby, in the oxidation step, the furan compound is oxidized to FDCA.

Further, the reaction liquid containing the furan compound has a pH of less than 9.0 in the oxidation step. Specifically, the pH of the reaction solution in the oxidation step is 7.0 to 9.0, preferably 7.0 to 8.4. This is because sodium hydrogen carbonate is added to the reaction solution in the present embodiment. That is, by adding sodium bicarbonate to a reaction liquid containing a furan compound, the reaction liquid becomes weakly alkaline, close to neutral. Oxidation of furan compounds proceeds in an alkaline environment.

In this embodiment, by using sodium bicarbonate, the pH of the aqueous solution is made into a slightly alkaline environment of less than 9.0. By oxidizing the furan compound in a weakly alkaline environment, the reaction temperature is set to a temperature close to room temperature. As described above, in the present embodiment, by oxidizing the furan compound in a weakly alkaline environment, it is possible to reduce the input energy.

(Suspension process)
The terminating step is a step of terminating oxidation of the furan compound. Excessive oxidation of the furan compound leads to the formation of impurities such as unintended by-products derived from the furan compound or the produced FDCA. Therefore, in the stopping step, the oxidation step is stopped by adding a reducing agent. Specifically, hypo (Na ₂ S ₂ O ₃ ), sodium sulfite (Na ₂ SO ₃ ), sodium hydrogen sulfite (NaHSO ₃ ), or the like can be used as the reducing agent added in the termination step. Note that the stopping step can be omitted. That is, by appropriately setting the amount of the oxidizing agent, all the oxidizing agent is consumed by the oxidation of the furan compound in the oxidation step. Therefore, if the amount of the oxidizing agent is set appropriately, the addition of the reducing agent can be omitted.

(Separation process)
The separation step is a step of separating FDCA remaining in the reaction solution. FDCA produced by oxidation of the furan compound is dissolved in the reaction solution in an alkaline environment. By concentrating the reaction solution under reduced pressure and adding an acid, the reaction solution becomes an acidic environment. As a result, FDCA dissolved in the reaction solution precipitates as crystals. At this time, any acid such as hydrochloric acid (HCl) or sulfuric acid (H ₂ SO ₄ ) can be used. The precipitated FDCA is collected, such as by filtration. The collected FDCA becomes a purified product through post-processes such as washing, recrystallization, and drying.

(Example)
Examples and comparative examples are described below. In Examples and Comparative Examples, the yield Y and purity P of the obtained FDCA were evaluated while changing conditions such as raw materials, catalysts, solvents, temperatures and reaction times to be used. The yield Y was calculated as Y=W1/W2×100 using the mass W1 of the material finally isolated after the separation step and the mass W2 of FDCA theoretically obtained as a chemical reaction. In addition, the purity P is obtained by proportionally dividing the ratio of the integrated values of the peaks with the impurities observed using NMR as FFCA and DKHDCA.
P = FDCA x 156.09/(FDCA x 156.09 + FFCA x 140.09 + DKHDCA x 172.09)
calculated as Here, the integrated value of the peak of FDCA (δ: 7.3 ppm) was set to 2H. The average value of the integrated values of the peaks of FFCA (δ: 7.4, 7.6, 9.8 ppm) was set to 1H. The integrated value of the peak of DKHDCA (δ: 6.7 ppm) was set to 2H. DKHDCA is Diketohexendicalboxylic Acid.

(Example 1)
Example 1 used mixing method A. In Example 1, as shown in FIG. 2, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 50 ml of water at room temperature with stirring to prepare a reaction solution. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 1 was 68%.

(Example 2)
Example 2 used mixing method A. In Example 2, as shown in FIG. 2, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 50 ml of water at room temperature with stirring to prepare a reaction solution. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 0.5 hours while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 2 was 83%.

(Example 3)
Example 3 used mixing method A. In Example 3, as shown in FIG. 2, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 50 ml of water at room temperature with stirring to prepare a reaction solution. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 24 hours while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 3 was 75%.

Examples 1-3 discuss the effect of reaction time in the oxidation step on the yield of FDCA. According to Examples 1 to 3, it can be seen that the reaction time in the oxidation step has little effect on the yield of FDCA. If the reaction time in the oxidation step is short, intermediates such as FFCA will be mixed in and the purity of the product will be reduced. Moreover, it is thought that if the reaction time in the oxidation step becomes longer, the oxidation reaction proceeds according to the amount of the oxidizing agent, and the generated FDCA is decomposed.

(Example 4)
Example 4 used mixing method A. In Example 4, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 50 ml of water at room temperature while stirring to prepare a reaction solution, as shown in FIG. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring with ice cooling at 10° C. or less. The reaction solution was stirred for 1 hour while being kept at 10° C. or lower under ice cooling, and 1 ml (1 mmol) of 10 mass % sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 4 was 91%.

(Example 5)
Example 5 used mixing method A. In Example 5, as shown in FIG. 3, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 50 ml of water at room temperature with stirring to prepare a reaction solution. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at 50°C. The reaction solution was stirred for 1 hour while maintaining the temperature at 50° C., and 1 ml (1 mmol) of 10 mass % sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 5 was 75%.

Examples 4-5 discuss the effect of reaction temperature on the yield of FDCA in the oxidation step. According to Examples 4 and 5, it can be seen that the lower the reaction temperature in the oxidation step, the higher the yield of FDCA. This is thought to be due to the fact that as the reaction temperature in the oxidation step rises, the formation of by-products other than FDCA proceeds and the decomposition of the formed FDCA proceeds.

(Example 6)
Example 6 used mixing method A. In Example 6, as shown in FIG. 4, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 25 ml of water at room temperature with stirring to prepare a reaction solution. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 6 was 68%.

(Example 7)
Example 7 used mixing method A. In Example 7, as shown in FIG. 4, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 5 ml of water at room temperature with stirring to prepare a reaction solution. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 7 was 37%.

Examples 6 and 7 discuss the effect of the amount of water used as a solvent in the reaction solution on the yield of FDCA. According to Examples 6 and 7, it can be seen that the amount of water used as a solvent affects the yield of FDCA. Example 6, in which the amount of water was half that of Example 1, which serves as a reference, did not significantly affect the yield. On the other hand, Example 7, in which the amount of water was 1/10 that of Example 1, had a lower yield. This is probably because the decrease in the amount of water causes unreacted FFCA and DKHDCA produced by excessive reaction to coexist in the solvent, thereby preventing the oxidation of FDCA.

(Example 8)
Example 8 used mixing method A. In Example 8, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 50 ml of water at room temperature while stirring to prepare a reaction solution as shown in FIG. To the reaction solution, 1.9 ml (3.0 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 8 was 74%.

(Example 9)
Example 9 used mixing method A. In Example 9, as shown in FIG. 5, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 50 ml of water at room temperature with stirring to prepare a reaction solution. To the reaction solution, 3.1 ml (5.0 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 2 ml (1.9 mmol) of 10 mass % sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 9 was 42%.

Examples 8-9 discuss the effect of the amount of oxidant added in the oxidation step on the yield of FDCA. According to Examples 8 and 9, it can be seen that the amount of oxidizing agent added in the oxidation step affects the yield of FDCA. That is, when the oxidizing agent was about 3 equivalents to 5-HMF, the yield of FDCA was almost the same as in Example 1, but unreacted FFCA was produced. From this, it is considered that the oxidizing agent is slightly insufficient when the amount of the oxidizing agent is about 3 equivalents to 5-HMF. On the other hand, when the oxidizing agent is in excess of about 5 equivalents to 5-HMF, the yield of FDCA decreases. It is considered that this is because when the oxidizing agent becomes excessive, the formation of by-products other than FDCA proceeds and the decomposition of the formed FDCA proceeds. In Example 9, the amount of reducing agent added in the stopping step is also changed according to the amount of oxidizing agent.

(Example 10)
Example 10 used mixing method A. In Example 10, as shown in FIG. 6, 126 mg (1 mmol) of 5-HMF as a furan compound, 7.8 mg (0.05 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 50 ml of water at room temperature with stirring to prepare a reaction solution. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 10 was 64%.

(Example 11)
Example 11 used mixing method A. In Example 11, as shown in FIG. 6, 126 mg (1 mmol) of 5-HMF as a furan compound, 1.6 mg (0.01 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium hydrogen carbonate were mixed with 50 ml of water at room temperature with stirring to prepare a reaction solution. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 11 was 75%.

Examples 10-11 discuss the effect of the amount of TEMPO on the yield of FDCA. According to Examples 10 and 11, it can be seen that the amount of TEMPO has little effect on the yield of FDCA as long as it is an amount that can contribute to the reaction in the oxidation step. However, since unreacted FFCA tends to increase when the amount of TEMPO is reduced, it is preferable to extend the reaction time in accordance with the decrease in TEMPO.

(Example 12)
Example 12 used mixing method A. In Example 12, as shown in FIG. 7, 140 mg (1 mmol) of FFCA as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analog, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 50 ml of water at room temperature with stirring to prepare a reaction solution. To the reaction solution, 0.6 ml (1.0 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (0.9 mmol) of 10 mass % sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 12 was 86%.

(Example 13)
Example 13 used mixing method A. In Example 13, 124 mg (1 mmol) of FDAL as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 590 mg (7 mmol) of sodium bicarbonate were mixed with 50 ml of water at room temperature while stirring to prepare a reaction solution, as shown in FIG. To the reaction solution, 1.2 ml (2.0 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (0.9 mmol) of 10 mass % sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 13 was 79%.

Examples 12-13 discuss the effect of the starting furan compound on the yield of FDCA. According to Examples 12 and 13, it can be seen that not only 5-HMF but also other furan compounds can be applied to this embodiment. In Examples 12 and 13, the amount of the oxidizing agent added in the oxidation step and the amount of the reducing agent added in the stopping step were changed according to the furan compound that was the raw material.

(Example 14)
Example 14 used mixing method A. In Example 14, as shown in FIG. 8, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 168 mg (2 mmol) of sodium hydrogen carbonate were mixed with 50 ml of water at room temperature with stirring to prepare a reaction solution. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 14 was 51%.

Example 14 discusses the effect of the amount of sodium bicarbonate added to the reaction solution on the yield of FDCA. According to Example 14, it can be seen that when the amount of sodium hydrogencarbonate contained in the reaction solution decreases, the yield of FDCA decreases, although oxidation of the furan compound proceeds. From this, it is considered that a weakly alkaline environment is suitable for oxidation of furan compounds.

(Example 15)
Example 15 used mixing method B. In Example 15, as shown in FIG. 9, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analog, and 590 mg (7 mmol) of sodium hydrogen carbonate were mixed with 50 ml of water at room temperature while stirring to prepare a reaction solution. While stirring the reaction solution at room temperature, 126 mg (1 mmol) of 5-HMF was added as a furan compound. At this time, 0.5 ml of 5-HMF was added as a 25.2 mass % aqueous solution. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Example 15 was 77%.

In Example 15, the mixing method B, in which the concentration of 5-HMF, which is a furan compound, was increased was discussed. As long as a sufficient amount of water, which is the solvent, is present in the reaction solution, 5-HMF can be oxidized by changing the mixing procedure even when the concentration of 5-HMF is high. Therefore, the oxidation of the furan compound can be promoted by selecting the mixing method A or the mixing method B depending on the concentration of 5-HMF supplied.

(Comparative example 1)
Comparative Example 1 used mixing method A. In Comparative Example 1, as shown in FIG. 10, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 50 ml of water were mixed with stirring at room temperature to prepare a reaction solution. That is, Comparative Example 1 does not contain sodium hydrogen carbonate, which makes the reaction solution weakly alkaline. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. As a result, FDCA precipitated as crystals in the reaction solution. The precipitated crystals were collected by filtration, washed twice with 1 ml of water, and dried under reduced pressure to obtain FDCA. The yield of FDCA in Comparative Example 1 was 28%.

Thus, it can be seen that Comparative Example 1, in which no sodium hydrogencarbonate is added, has a lower yield. This is probably because the pH of the reaction solution tends to be less acidic than 7.0 when sodium hydrogencarbonate is not added, which hinders the oxidation of 5-HMF.

(Comparative example 2)
Comparative Example 2 used mixing method A. In Comparative Example 2, as shown in FIG. 10, 126 mg (1 mmol) of 5-HMF as a furan compound, 15.6 mg (0.1 mmol) of TEMPO as a TEMPO analogue, and 280 mg (7 mmol) of sodium hydroxide were mixed with 50 ml of water at room temperature with stirring to prepare a reaction solution. That is, Comparative Example 2 contains sodium hydroxide instead of sodium bicarbonate. Therefore, in the case of Comparative Example 2, the reaction solution is in a strongly alkaline environment with a pH of 10 or more. To the reaction solution, 2.0 ml (3.2 mmol) of a 12% by mass sodium hypochlorite aqueous solution was added as an oxidizing agent while stirring at room temperature. The reaction solution was stirred for 1 hour while being maintained at room temperature, and 1 ml (1 mmol) of 10% by mass sodium hydrogen sulfite was added as a reducing agent to stop the reaction in the oxidation step.

The reaction solution was concentrated under reduced pressure, adjusted to 10 ml with water, and acidified with 1 ml of concentrated hydrochloric acid. In the case of Comparative Example 2, almost no crystals were deposited in the reaction solution even in an acidic environment. Therefore, after the filtrate from which the crystals were separated was concentrated under reduced pressure to dryness, a brown powder was obtained. Although this brown powder contained an NMR peak thought to be FDCA, it was a very small amount and was a mixture of multiple components.

Thus, in Comparative Example 2 using sodium hydroxide as an alkali source, almost no FDCA was obtained. This is probably because Comparative Example 2, in which sodium hydroxide was added, was in a strongly alkaline environment, and the side reactions proceeded predominantly over the oxidation of 5-HMF.

As described above, it can be seen from Comparative Examples 1 and 2 that the desired oxidation of 5-HMF is promoted and the yield of FDCA is improved by making the reaction solution a weakly alkaline environment with a pH of less than 9.0 using sodium bicarbonate as in the present embodiment.

Claims (4)

a mixing step of mixing a furan compound, a TEMPO analogue, sodium bicarbonate, and an oxidizing agent with water at 50° C. or less to produce a reaction liquid;
an oxidation step of stirring the reaction solution at a reaction temperature of 0 to 50° C. and a reaction time of 0.5 to 24 hours to oxidize the furan compound to produce furandicarboxylic acid (FDCA);
A separation step of adding an acid to the reaction solution after the oxidation step to make it acidic, and precipitating the FDCA dissolved in the reaction solution;
A method of manufacturing FDCA comprising: The mixing step includes a first mixing step of mixing the furan compound, the TEMPO analog and the sodium hydrogen carbonate with water;
a second mixing step of adding the oxidizing agent to the aqueous solution generated in the first mixing step;
The method for producing FDCA according to claim 1, comprising: The mixing step includes a first mixing step of mixing the TEMPO analogue, the sodium bicarbonate and the oxidizing agent with water;
a second mixing step of adding the aqueous solution of the furan compound to the aqueous solution mixed in the first mixing step;
The method for producing FDCA according to claim 1, comprising: The method for producing FDCA according to any one of claims 1 to 3, wherein the reaction temperature in the oxidation step is room temperature of 20 to 35°C.

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