A method for carboxylating the vinyl group of styrenes having a hydroxyl or amino group attached to an aryl group.

Abstract

The present invention provides a method for carboxylating the vinyl group of styrenes having an aryl group with a hydroxyl group or an amino group by fixing carbon dioxide through an electrochemical reaction with carbon dioxide. [Solution] By adding water to an electrochemical reaction system between styrenes having an aryl group and a hydroxyl group or an amino group and carbon dioxide, carbon dioxide is immobilized, thereby carboxylating the vinyl group of the styrenes.

Description

Technical Field

[0001] The present invention relates to a method for carboxylating a vinyl group of styrenes having a hydroxy group or an amino group on an aryl group, and particularly relates to a method for carboxylating the vinyl group by immobilizing carbon dioxide through an electrochemical reaction between the styrenes and carbon dioxide.

Background Art

[0002] In recent years, as global warming caused by carbon dioxide emitted into the atmosphere has become a worldwide problem, technological development of effective utilization methods for the emitted carbon dioxide has been actively promoted. Among them, one of the promising utilization methods is to use carbon dioxide as a chemically useful carbon source. In particular, the carboxylation of olefins using carbon dioxide is a useful method that can not only introduce a strong C-C bond but also efficiently convert abundant and easily available olefin compounds into carboxylic acids.

[0003] However, since carbon dioxide is a very stable substance, in order to use it in a chemical reaction, highly reactive and difficult-to-handle reagents or multi-step processes were required. Therefore, in recent years, a method for synthesizing high-value-added carboxylic acids by electrochemically reacting various olefin compounds with carbon dioxide has been developed. For example, Non-Patent Document 1 discloses a method for carboxylating by reacting a vinyl group of various olefin compounds with carbon dioxide in an electrochemical reaction system using a graphite electrode and adding an additive.

Prior Art Documents

Non-Patent Documents

[0004]

Non-Patent Document 1

Summary of the Invention

[0005] There is a need for methods to obtain high-value carboxylic acids by carboxylating vinylphenols, which are a type of olefin compound readily available from biomass raw materials, and aminostyrenes, which can similarly be derived from biomass. However, it has been shown that in conventional electrochemical reaction systems, even when attempting to fix carbon dioxide to compounds having a hydroxyl or amino group attached to an aryl group, the desired carboxylation reaction does not proceed (Poor Reactivity) (see Non-Patent Literature 1: page 1781, left column, bottom 3-1 lines; page 1782, left column, Table 2. Terminal olefins). Therefore, it has been difficult to carboxylate the vinyl group of compounds having a hydroxyl or amino group attached to an aryl group using conventional electrochemical methods. The object of this invention is to provide a method for carboxylating the vinyl group of styrenes having an aryl group with a hydroxyl group or an amino group by fixing carbon dioxide through an electrochemical reaction between the styrenes and carbon dioxide. [Means for solving the problem]

[0006] As a result of diligent research to solve the aforementioned problems, the present inventors discovered that by actively adding water, which is generally considered to be removed in electrochemical reactions of organic compounds, the carboxylation reaction of styrenes having a hydroxyl group or an amino group on an aryl group can be carried out, leading to the present invention. In other words, the present invention for solving the above problems includes the following embodiments. [1] A method of carboxylating the vinyl group of a styrene represented by the following general formula (1) by adding water to an electrochemical reaction system of carbon dioxide. [ka] (In the formula, each R1 independently represents a hydroxyl group, an amino group, a hydrogen atom, a C1-C20 alkyl group, or a C1-C20 alkoxy group, with at least one of R1 being a hydroxyl group or an amino group, and each R2 independently represents a hydrogen atom or a C1-C20 alkyl group.) [2] The method of [1], wherein the amount of water added is 2,000 to 10,000 ppm relative to the reaction solution. [3] The method of [1] or [2], wherein the reaction temperature of the electrochemical reaction system is 25°C or lower. [4] The method of [1] or [2], wherein the reaction of the electrochemical reaction system is carried out under a constant current. [5] The method of [1] or [2], wherein the electrochemical reaction system comprises tetraethylammonium p-toluenesulfonate. [Effects of the Invention]

[0007] The present invention provides a method for carboxylating styrenes having an aryl group with a hydroxyl or amino group by immobilizing carbon dioxide. Furthermore, since many biomass-derived materials have phenol and alkene moieties, applying the method of the present invention to biomass-derived materials may allow for the synthesis of more environmentally friendly materials composed solely of biomass and carbon dioxide, which are renewable resources, in addition to carbon dioxide immobilization. Moreover, since carboxylic acids having an aryl group with an amino group can be used as precursors for pharmaceuticals, the present invention may be useful as a new synthesis method for them. [Brief explanation of the drawing]

[0008] [Figure 1] Schematic diagram of the electrochemical reaction system in the present invention [Figure 2] Schematic diagram of the electrochemical reaction system in the conventional method [Modes for carrying out the invention]

[0009] Hereinafter, embodiments of the present invention (hereinafter referred to as "the present embodiment") will be described. However, these are for explaining the present invention and do not limit the scope of the present invention. The present invention includes various embodiments and modifications thereof. The scope of the present invention is indicated by the claims, and various modifications made within the scope of the claims and within the scope of technical means equivalent thereto are considered to be within the scope of this invention. When a numerical range or the like is represented using "~", it means including the numerical values described as the lower limit and the upper limit.

[0010] [Styrenes having a hydroxy group or an amino group on an aryl group] The styrenes having a hydroxy group or an amino group on an aryl group according to the present invention are as shown in the following general formula (1).

[0011] [Chemical formula] (In the formula, each R1 independently represents a hydroxy group, an amino group, a hydrogen atom, an alkyl group having 1 to 20 carbon atoms, or an alkoxy group having 1 to 20 carbon atoms, and at least one of R1 is a hydroxy group or an amino group, and each R2 independently represents a hydrogen atom or an alkyl group having 1 to 20 carbon atoms.) Hereinafter, the styrenes represented by the general formula (1) may be simply referred to as "styrenes".

[0012] In the present embodiment, the styrenes include, for example, vinylphenols, dihydroxystyrenes, trihydroxystyrene, and 4-aminostyrene shown in the following formula.

[0013] [Chemical formula]

[0014] [Carboxylation of vinyl group] In the electrochemical reaction system according to this embodiment, the carboxylation of the vinyl group is represented by the following formula, taking 4-vinylphenol shown in the upper left as an example of the reaction substrate. As shown in the following formula, carbon dioxide reacts with the vinyl group to carboxylate it, producing β-4-hydroxyphenylpropanoic acid (β-HPPA) and α-4-hydroxyphenylpropanoic acid (α-HPPA). The reaction conditions shown in the following formula are those of Example 18, which will be described later.

[0015] [ka]

[0016] [Electrochemical reaction system] In the electrochemical reaction system according to this embodiment, the electrodes used can be either a combination of graphite for both the cathode and anode, or a combination of Ni-graphite and Pt-graphite, but it is preferable in terms of yield if both electrodes are graphite.

[0017] The reaction system contains an electrolyte along with the styrene reaction substrate. Examples of electrolytes include tetraethylammonium iodide (Et4NI), tetraethylammonium p-toluenesulfonate (Et4NOTs), tetraethylammonium bromide (Et4NBr), tetraethylammonium chloride (Et4NCl), tetrabutylammonium iodide (Bu4NI), tetraethylammonium tetrafluoroborate (Et4NBF4), and lithium tetrafluoroborate (LiBF4). In particular, in the present invention, the use of Et4NOTs is preferred because it increases reactivity.

[0018] In addition, it is preferable to add the following as a protonating agent: triethanolamine (TEOA), ethanolamine, methanol, ethanol, 2-propanol, etc., and as a reaction solvent: N,N-dimethylformamide (DMF), N,N-dimethylacetamide, N-methyl-2-pyrrolidone, etc.

[0019] Water is further added to the reaction system. The amount of water added is preferably 100 ppm or more relative to the reaction solution, more preferably 2000 ppm or more. It is also preferable that it be 10000 ppm or less. Within this preferred range, the target carboxylic acid can be obtained with higher yield and better selectivity. Water is thought to act as a sacrificial oxidizing agent in the reaction between the substrate and carbon dioxide, which will be detailed below.

[0020] [Reaction with carbon dioxide] Carbon dioxide is blown into the electrochemical reaction system described above, and after thorough stirring, the electrochemical reaction is carried out. The stirring and reaction temperature is preferably 25°C or lower, more preferably 5°C or lower, and even more preferably 0°C or lower. Keeping the temperature below 25°C helps to suppress unwanted side reactions. Electrochemical reactions can be carried out using either a constant current or a constant voltage. However, when using a constant voltage, the current value changes constantly, making it difficult to adjust the amount of electrons injected, which is calculated as (current value × reaction time). In contrast, when using a constant current, the amount of electrons injected can be easily adjusted. When using a constant current, the voltage is 2V to 10V, and the current density is 2.0mA to 20mA / cm². 2 (A current value of 10 to 100 mA is preferable.) When using a constant voltage, it is preferable to use a voltage of 5V or more and less than 20V, with a current density of 10 to 20 mA / cm². 2 This is preferable. If the voltage is less than 20V, the reduction reaction of the vinyl group, which is a side reaction, can be suppressed as it will not proceed preferentially.

[0021] [The effects of water] Figure 1 is a schematic diagram of the electrochemical reaction system to which water is added in the present invention, and Figure 2 is a schematic diagram of the electrochemical reaction system to which water is not added in the conventional method. Figures 1 and 2 show 4-vinylphenol as a styrene compound and β-4-hydroxyphenylpropanoic acid as the carboxylated target product.

[0022] The water added to the electrochemical reaction system in this invention acts as a sacrificial oxidation reagent and can inhibit the oxidation reaction of the hydroxyl group on the anode side. That is, as shown in Figure 1, the preferential oxidation of water suppresses the oxidation of the hydroxyl group of 4-vinylphenols on the anode side. This creates a highly reactive quinone methide intermediate, and the reaction that would result from further side reactions from this intermediate is suppressed (indicated by "×"). On the other hand, the reaction shown on the cathode side of Figure 1, that is, the reaction in which electrons are supplied to the alkene moiety of 4-vinylphenols to form a radical anion intermediate, carbon dioxide is immobilized on the highly reactive radical anion intermediate, and the reaction that produces the carboxylated target product can be promoted.

[0023] In contrast, in the conventional method where the electrochemical reaction is carried out without the addition of water, the reaction on the anode side, as shown in Figure 2, is thought to occur preferentially. That is, the hydroxyl group of 4-vinylphenols is oxidized on the anode side to create a highly reactive quinone methide intermediate, and further side reactions are thought to be induced from this intermediate. The desired carboxylation on the cathode side hardly occurs, as indicated by the "×". [Examples]

[0024] The present invention will be described below with reference to examples, but the present invention is not limited to the following examples. Any changes to materials, processing conditions, etc., within the scope of the technical concept of the present invention are also included in the present invention. In Examples 1-13, the reaction was carried out under constant voltage conditions, while in Examples 14-28, the reaction was carried out under constant current conditions. The specific gravity of water was assumed to be 1.

[0025] (Example 1: Constant voltage conditions) In an electrolytic cell equipped with graphite electrodes as cathode and anode, 1.0 mmol of 4-vinylphenol, 0.5 mmol of Et4NI, 1.0 mmol of TEOA, and 10 mL of DMF were added, along with 1.1 mmol of water (20 μL: 2000 ppm). The mixture was stirred at 5°C while bubbling carbon dioxide (1 atm, 50 ccm). After 1 hour, the electrochemical reaction according to Example 1 was carried out under constant voltage of 10 V using a DC stabilized power supply for 3 hours to obtain a carboxylic acid. Analysis using gas chromatography (GC) revealed a yield of 22% of the target carboxylic acid. The obtained carboxylic acid was identified as 4-hydroxyphenylpropanoic acid by nuclear magnetic resonance (NMR) spectroscopy.

[0026] (Examples 2-7, amount of water added) Except for changing the amount of water added to 1, 10, 30, 40, 50, or 100 μL, the electrochemical reactions according to Examples 2 to 7 were carried out under the same conditions as in Example 1, and the yield of carboxylic acid was determined.

[0027] (Comparative Example 1) The electrochemical reaction according to Comparative Example 1 was carried out under the same conditions as in Example 1, except that water was not added, and the yield of carboxylic acid was determined.

[0028] (Example 8: Reaction time) The electrochemical reaction according to Example 8 was carried out under the same conditions as in Example 1, except that the reaction time was extended to 6 hours, and the yield of the carboxylic acid was determined. Furthermore, silica gel column chromatography (dichloromethane:ethyl acetate:acetic acid = 69:30:1) was performed to determine the yield of 4-hydroxyphenylpropanoic acid.

[0029] (Example 9: Reaction Temperature) The electrolytic reaction according to Example 9 was carried out under the same electrolytic reaction conditions as in Example 1, except that the stirring and electrolytic reaction temperature were changed to 25°C, and the yield of carboxylic acid was determined by GC analysis.

[0030] (Examples 10 and 11: Electrodes) Except for using the electrodes shown in Table 2 as the cathode and anode, the electrolytic reactions according to Examples 10 and 11 were carried out under the same electrolytic reaction conditions as in Example 1, and the yield of the target product was determined by GC analysis. The reaction conditions, yield, and selectivity for Examples 1 to 11 and Comparative Example 1 are shown in Table 1 below.

[0031] [Table 1] Conversion rate: (Amount of substrate charged - Amount of substrate after reaction) / Amount of substrate charged × 100 Selectivity: Yield / Conversion Rate × 100

[0032] From the results in Table 1, it was found that in the electrochemical reaction system of Comparative Example 1, where no water was added, almost no carboxylic acid was obtained. However, in the electrochemical reaction systems to which approximately 100 ppm or approximately 1000 ppm of water was added, a small amount of carboxylic acid was obtained. In particular, in Examples 1 and 4-7, where the water content was between 2000 ppm and 10000 ppm, the yield and selectivity were significantly superior. In the electrochemical reaction system of Example 8, where the reaction time was extended to 6 hours, the conversion rate reached 100%, and it was found that carboxylic acids were obtained in a higher yield than in Example 1, where the reaction time was 3 hours. In Example 9, where the reaction temperature was 25°C, the yield was 5.5%, which was higher than that of Comparative Example 1, but lower than that of Example 1, where the reaction temperature was 5°C and all other conditions were the same. This is thought to be because the higher reaction temperature increased the probability of undesirable side reactions on the anode side. While carboxylic acids can be obtained using the anode and cathode combinations in Examples 10 and 11, it was found that the yield was higher in Example 1, where both the anode and cathode were graphite. In the following examples, comparative examples, and reference examples, the electrochemical reaction was carried out using graphite at both electrodes.

[0033] (Examples 12 and 13: Substrates) Except for changing the substrate to 2-methoxy-4-vinylphenol or 2,6-dimethoxy-vinylphenol, the electrochemical reactions according to Example 12 or 13 were carried out under the same electrochemical reaction conditions as in Example 8, and the yield of the obtained carboxylic acid was determined. In Example 12, the yield of the target carboxylic acid was 20%, and in Example 13, the yield of the carboxylic acid was 24%, indicating that the carboxylation reaction by carbon dioxide fixation according to the present invention is effective for 4-vinylphenols in general. The obtained carboxylic acids were identified by NMR analysis as 3-(4-hydroxy-3-methoxyphenyl)propanoic acid or 3-(4-hydroxy-3,5-dimethoxyphenyl)propanoic acid, respectively.

[0034] In the following examples, reference examples, and comparative examples, the procedures were carried out under constant current conditions that allowed for easy adjustment of the electron injection amount (current value × reaction time).

[0035] (Reference Examples 1-6: Selection of Electrolytes) To investigate the change in yield when the electrolyte is changed, the same substrate (4-vinylphenol) as in Example 1 was used, and an electrochemical reaction was carried out under the conditions of a current of 100 mA, a reaction temperature of 0°C, and a reaction time of 60 minutes, using the electrolytes shown in Table 2 below. However, since no water was added to the reaction system, these are considered reference examples of the present invention. The results are shown in Table 2 below.

[0036] [Table 2]

[0037] From the above examples, it was found that when Et4NOTs are used as the electrolyte, the conversion rate is not particularly high, but the selectivity for carboxylic acid formation is high, and the yield, especially the yield of β-HPPA, is excellent.

[0038] (Example 14: Amount of water added, reduced current) Using the electrolyte Et4NOTs, which yielded a high yield in the above reference example, the reaction temperature was set to 0°C to minimize side reactions, the reaction time to 12 hours, and the current value to 10 mA (current density 2 mA / cm²). 2 With the conditions fixed, electrochemical reactions were carried out with varying amounts of water added: 0 (Comparative Example 2), 0.5, 1.0, 5.0, and 10.0 mmol (Examples 14-1 to 14-4). Electrochemical reactions were also carried out for Example 14-5, which contained no TEOA and had 1.0 mmol of water added, and for Comparative Example 3, which contained no TEOA and had ethanol (EtOH) added instead of water. The results are shown in Table 3.

[0039] [Table 3]

[0040] According to Table 3, a comparison between Comparative Example 2 and Examples 14-1 to 14-4 shows that when the electrolyte is Et4NOTs, the target carboxylic acid can be obtained in sufficient yield by adding water, even at a low current value of 10 mA. Furthermore, Example 14-5 showed that while TEOA in the reaction system is not essential, it contributes to a higher yield. Comparative Example 3 showed that substituting water with ethanol does not contribute to an improvement in yield.

[0041] (Example 15: Current value and reaction time) To determine the optimal current value and reaction time when the electron injection amount (current value × reaction time) is kept constant, the electrochemical reactions according to Examples 15-1 to 15-7 were carried out under the conditions shown in Table 4, with the electrolyte Et4NOTs (0.5 mmol), TEOA (1.0 mmol), water (5 mmol), and reaction temperature 0°C being standardized.

[0042] [Table 4]

[0043] From the results in Table 4, when the electron injection amount is equal, the current value is 30 mA (current density 6 mA / cm²).2 ) It was found that carrying out the electrochemical reaction for 214 minutes was optimal in terms of both conversion rate and yield, and in particular, the yield of β-HPPA was high.

[0044] (Examples 16-18: Electrolytes) In the above reference example, the suitability of the electrolyte without water was investigated. However, in this example, the electrochemical reaction was carried out under the same reaction conditions as shown in the table below, except that the type of electrolyte (Et4NI and Et4NOTs) and the amount of electrolyte were changed when water was added. Note that Example 17 is the same as Example 15-5.

[0045] [Table 5]

[0046] Table 5 shows that even when water is added, using Et4NOTs as the electrolyte results in a better yield than using Et4NI, and that adding 1.0 mmol of Et4NOTs slightly improves the yield from 61.1% to 64.6%.

[0047] (Examples 19-27: Substrates) The substrate was changed to styrenes having a hydroxyl or amino group attached to the aryl group, as shown in Table 6, and the electrochemical reaction was carried out using the optimal constant current conditions (electrode (-)C (+)C, electrolyte Et4NOTs (1.0 mmol), TEOA (1.0 mmol), DMF (10 mL), water 5.0 mmol (9000 ppm), reaction temperature 0°C, current value 30 mA) determined from Examples 14-18 above. The results are shown in Table 6. Note that the reaction time was adjusted because the amount of electrons injected into the reaction needed to be changed depending on the number of functional groups.

[0048] [Table 6]

[0049] From the above results, it was found that the carboxylation reaction by carbon dioxide fixation according to the present invention is effective in common with styrenes having a hydroxyl group or an amino group attached to the aryl group. [Industrial applicability]

[0050] According to the present invention, a method for carboxylation can be provided by immobilizing carbon dioxide onto styrenes having an aryl group with a hydroxyl group or an amino group. Since styrenes having an aryl group with a hydroxyl group or an amino group are readily available as biomass raw materials or derivatives thereof, this method has high potential to contribute to carbon dioxide immobilization, and to the modification and functionalization of biomass using only renewable resources such as biomass and carbon dioxide.

Claims

1. A method for carboxylating the vinyl groups of styrenes represented by the following general formula (1) by adding water to an electrochemical reaction system of carbon dioxide and styrenes. 【Chemistry 1】 (In the formula, R １ Each of these independently represents a hydroxyl group, an amino group, a hydrogen atom, a C1-C20 alkyl group, or a C1-C20 alkoxy group, R １ At least one of them is a hydroxyl group or an amino group, R ２ Each of these independently represents either a hydrogen atom or an alkyl group having 1 to 20 carbon atoms.

2. The method according to claim 1, wherein the amount of water added is 2,000 to 10,000 ppm relative to the reaction solution.

3. The method according to claim 1 or 2, wherein the reaction temperature of the electrochemical reaction system is 25°C or lower.

4. The method according to claim 1 or 2, wherein the reaction of the electrochemical reaction system is carried out under a constant current.

5. The method according to claim 1 or 2, wherein the electrochemical reaction system comprises tetraethylammonium p-toluenesulfonate.

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