Electrocatalytic synthesis of tetramethylpyrazine

Abstract

The application discloses an electrocatalytic synthesis method of tetramethylpyrazine, which comprises the following steps: dissolving ethylidene glycerin and an ammonium salt in a buffer solution, and introducing air; taking a Cu-based catalyst as a positive electrode and a negative electrode, and performing reaction under the action of a voltage of 1.2-1.6 V to obtain 2,3,5,6-tetramethylpyrazine. The electrocatalytic synthesis method effectively promotes the cyclization and dehydrogenation reaction under mild conditions, reduces the wastewater discharge, and realizes the construction of the electrocatalytic green synthesis route of 2,3,5,6-tetramethylpyrazine.

Description

TECHNICAL FIELD

[0001] The application belongs to the technical field of organic compound synthesis, and particularly relates to an electrocatalytic synthesis method of tetramethylpyrazine. BACKGROUND

[0002] 2,3,5,6-tetramethylpyrazine (TTMP) is an important organic nitrogen heterocyclic compound, also known as tetramethylpyrazine, which exists in products such as liquor, soy products, coffee, dairy products, etc., has a special aroma similar to popcorn, nuts and fruits, and can be used as a food additive to enhance aroma. In addition, TTMP has been widely used in China for the treatment of cardiovascular diseases such as hypertension. It has a good protective effect on cardiovascular diseases and inhibits thrombus formation.

[0003] The molecular formula of TTMP is C8H 12 N2, the molecular weight is 136.2, the melting point is 82-84℃, it is a white crystalline powder, soluble in ethanol, most non-volatile oils and propylene glycol, and slightly soluble in water. The structural formula of TTMP is shown as formula I.

[0004] (Formula I)

[0005] There are three major categories of existing production methods of TTMP, namely plant extraction method, biological synthesis method and chemical synthesis method. The plant extraction method is to extract from the rhizome of Chinese chuanxiong rhizome, but due to the extremely low content of TTMP (~0.075%) and the limited supply of plant raw materials, the extraction process is complex and difficult to produce on a large scale; the biological synthesis method is to use sugar raw materials to produce acetoin through microbial strain fermentation, and then react with ammonium salt in the fermentation broth to produce TTMP, which still has certain difficulties in large-scale production.

[0006] The chemical synthesis method is the main method for industrial production at present. There are many common synthesis methods: one-step method using alcohol, amine or alcohol amine as raw material for catalytic condensation under gas phase conditions to obtain TTMP, but the reaction temperature is high (300-500℃) and the selectivity is low; two-step method using o-diketone and o-diamine as raw materials, first condensing to obtain dihydropyrazine, and then catalytically dehydrogenating to obtain TTMP, the two-step method has higher yield and better product purity than the one-step method, but the operation conditions are higher and the by-products are difficult to separate, so the production cost is high; acetoin reacts with ammonium salt to produce TTMP, the reaction mechanism is shown in formula II. Acetoin reacts with ammonium to dehydrate, and then cyclizes and dehydrates to obtain TTMP. However, there are problems such as low yield and harsh reaction conditions.

[0007] (Formula II)

[0008] CN104341359A reports a preparation method of tetramethylpyrazine, which uses butanedione monoxime as a raw material, reacts with ammonium formate under the condition of palladium-carbon catalyst, reflux stirs, removes the catalyst after the reaction is completed, extracts with dichloromethane after cooling, and obtains tetramethylpyrazine by vacuum concentration, with a yield of more than 80%. However, the steps are complicated, and the amount of waste is large.

[0009] CN117510417A reports a method for improving the yield of tetramethylpyrazine by Fenton reaction, which obtains tetramethylpyrazine in a low-pollution, low-production-cost and low-reaction-temperature manner, but uses hydrogen peroxide precursor, and the reaction efficiency is affected by the decomposition efficiency of hydrogen peroxide, and the cost is high. SUMMARY

[0010] This part aims to summarize some aspects of the embodiments of the present application and briefly introduce some preferred embodiments. Some simplifications or omissions may be made in this part and the abstract and title of the specification to avoid obscuring the purpose of this part, the abstract and the title, and such simplifications or omissions cannot be used to limit the scope of the present application.

[0011] In view of the above and / or problems existing in the prior art, the present application is proposed.

[0012] One of the purposes of the present application is to provide an electrocatalytic synthesis method of tetramethylpyrazine. The preparation method provided by the present application is simple in operation, low in production cost, and less in wastewater.

[0013] To solve the above technical problems, the present application provides the following technical scheme: an electrocatalytic synthesis method of tetramethylpyrazine, comprising,

[0014] Dissolve acetonine and ammonium salt in a buffer solution, and pass in air, use Cu-based catalyst as an anode and a cathode, and react under the action of a voltage of 1.2-1.6V to obtain 2,3,5,6-tetramethylpyrazine.

[0015] The Cu-based catalyst comprises Cu and a second metal, and the second metal is selected from one of Ni, Mg and Zn.

[0016] As a preferred scheme of the electrocatalytic synthesis method of tetramethylpyrazine, in the Cu-based catalyst, the molar ratio of Cu to the second metal is 10:1.

[0017] As a preferred scheme of the electrocatalytic synthesis method of tetramethylpyrazine, the buffer solution has a pH value of 3-8 and is obtained by mixing diammonium hydrogen phosphate solution and ammonium dihydrogen phosphate solution, and the concentration of the diammonium hydrogen phosphate solution and the ammonium dihydrogen phosphate solution is 0.2mol / L.

[0018] As a preferred scheme of the electrocatalytic synthesis method of tetramethylpyrazine, in the scheme, the molar ratio of the ethanedione to the ammonium salt is 1:1.1-2.

[0019] As a preferred scheme of the electrocatalytic synthesis method of tetramethylpyrazine, in the scheme, the ammonium salt is one or more of the following: an aqueous solution of ammonium acetate, ammonium sulfate, ammonium citrate, ammonium phosphate.

[0020] As a preferred scheme of the electrocatalytic synthesis method of tetramethylpyrazine, in the scheme, the ammonium salt is an aqueous solution of ammonium acetate and ammonium phosphate, and the molar ratio of the ammonium acetate to the ammonium phosphate is 0.1-1:1.

[0021] As a preferred scheme of the electrocatalytic synthesis method of tetramethylpyrazine, in the scheme, the reaction is carried out at a temperature of 30-60 DEG C for 4-8 hours.

[0022] As a preferred scheme of the electrocatalytic synthesis method of tetramethylpyrazine, in the scheme, the air is introduced at a flow rate of 10-40 mL / min.

[0023] As a preferred scheme of the electrocatalytic synthesis method of tetramethylpyrazine, in the scheme, the Cu-based catalyst is prepared by a deposition precipitation method, a Cu mesh is used as a substrate, an aqueous solution of Ni(NO3)2, Mg(NO3)2 and Zn(NO3)2 is used as a second metal precursor, and sodium hydroxide is used as a precipitant to deposit one of Ni, Mg and Zn on the Cu mesh.

[0024] As a preferred scheme of the electrocatalytic synthesis method of tetramethylpyrazine, in the scheme, the Cu mesh used in the Cu-based catalyst has a mesh number of 200-600.

[0025] Compared with the prior art, the application has the following beneficial effects:

[0026] The electrocatalytic method can promote the reactions of amination, ring formation and dehydrogenation of dihydrotetramethylpyrazine, and has the advantages of mild reaction conditions, high catalyst efficiency, and recyclable catalyst and buffer solution, thus forming a new green preparation technology of tetramethylpyrazine. BRIEF DESCRIPTION OF DRAWINGS

[0027] In order to more clearly illustrate the technical solutions of the embodiments of the application, the following will briefly introduce the drawings needed in the embodiment description. Obviously, the drawings in the following description are only some embodiments of the application, and other drawings can be obtained by those skilled in the art without any creative labor. Among them:

[0028] Figure 1A comparison chart of the yield of 2,3,5,6-tetramethylpyrazine under different reaction conditions of the present application. DETAILED DESCRIPTION

[0029] In order to make the above objectives, features and advantages of the present application more obvious and easy to understand, the specific embodiments of the present application will be described in detail below with reference to the embodiments of the present application.

[0030] In the following description, a large number of specific details are set forth in order to facilitate a thorough understanding of the present application, but the present application can also be implemented in other ways different from those described herein, and those skilled in the art can make similar generalizations without departing from the concept of the present application, therefore the present application is not limited to the specific embodiments disclosed below.

[0031] Secondly, "one embodiment" or "embodiment" referred to herein means that a specific feature, structure or characteristic can be included in at least one implementation of the present application. "In one embodiment" appearing in different places in the specification does not mean the same embodiment, nor is it an embodiment that is separate or alternative to other embodiments.

[0032] Unless otherwise specified, the raw materials used in the examples are commercially purchased.

[0033] First, a 0.2 mol / L diammonium hydrogen phosphate and 0.2 mol / L ammonium dihydrogen phosphate aqueous solution were prepared in a volumetric flask, and then the two solutions were mixed to form a buffer solution.

[0034] At room temperature, two pieces of 300-mesh 6 cm x 3 cm Cu mesh were placed in a 200 mL beaker as a substrate, and 0.05 mol / L Ni(NO3)2 or Mg(NO3)2 or Zn(NO3)2 aqueous solution was used as the second metal precursor, and one of Ni, Mg and Zn was deposited on the Cu mesh. 40 mL of the above salt solution was added to the beaker to ensure that the copper mesh was completely covered with the solution, and the copper mesh was stirred together, the stirring speed was 500 rpm, the precipitant was sodium hydroxide, the concentration was 0.1 mol / L, 40 mL of sodium hydroxide solution was added dropwise to the beaker, the dropwise adding speed was 0.5 mL / min, and after the dropwise adding was completed, the beaker was aged for 12 h. After the deposition and precipitation were completed, the Cu mesh was taken out, washed with deionized water 10 times, each time 30 mL, and then dried in a vacuum drying oven at 60°C for 12 h, thereby obtaining Cu-Ni, Cu-Mg and Cu-Zn catalysts, which were then used as anode and cathode for electrochemical reaction.

[0035] Example 1

[0036] In a 6cm x 3cm x 6cm single-chamber electrolytic cell reactor, acetyl, ammonium acetate is dissolved in a buffer solution, the ratio is 1:1.2, the air flow is 20 mL / min, the reaction is carried out at a reaction temperature of 40°C, Cu-Zn catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine is obtained, which is quantitatively analyzed by liquid chromatography, and the yield is 49%.

[0037] Example 2

[0038] In a 6cm x 3cm x 6cm single-chamber electrolytic cell reactor, acetyl, ammonium acetate is dissolved in a buffer solution, the ratio is 1:1.5, the air flow is 20 mL / min, the reaction is carried out at a reaction temperature of 40°C, Cu-Zn catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine is obtained, which is quantitatively analyzed by liquid chromatography, and the yield is 51%.

[0039] Example 3

[0040] In a 6cm x 3cm x 6cm single-chamber electrolytic cell reactor, acetyl, ammonium acetate is dissolved in a buffer solution, the ratio is 1:1.5, the air flow is 20 mL / min, the reaction is carried out at a reaction temperature of 50°C, Cu-Zn catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine is obtained, which is quantitatively analyzed by liquid chromatography, and the yield is 58%.

[0041] Example 4

[0042] In a 6cm x 3cm x 6cm single-chamber electrolytic cell reactor, acetyl, ammonium acetate is dissolved in a buffer solution, the ratio is 1:1.5, the air flow is 20 mL / min, the reaction is carried out at a reaction temperature of 60°C, Cu-Zn catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine is obtained, which is quantitatively analyzed by liquid chromatography, and the yield is 55%.

[0043] Example 5

[0044] In a 6cm x 3cm x 6cm single-chamber electrolytic cell reactor, acetyl, ammonium acetate is dissolved in a buffer solution, the ratio is 1:1.5, the air flow is 20 mL / min, the reaction is carried out at a reaction temperature of 60°C, Cu-Zn catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine is obtained, which is quantitatively analyzed by liquid chromatography, and the yield is 55%.

[0045] Example 6

[0046] In a 6cm x 3cm x 6cm single-compartment electrolytic cell reactor, acetyl, ammonium acetate was dissolved in buffer solution, the ratio was 1:1.5, the air flow was 20 mL / min, the reaction was carried out at a reaction temperature of 50°C, Cu-Mg catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine was obtained, which was quantitatively analyzed by liquid chromatography, and the yield was 39%.

[0047] Example 7

[0048] In a 6cm x 3cm x 6cm single-compartment electrolytic cell reactor, acetyl, ammonium acetate was dissolved in buffer solution, the ratio was 1:1.5, the air flow was 20 mL / min, the reaction was carried out at a reaction temperature of 50°C, Cu-Mg catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine was obtained, which was quantitatively analyzed by liquid chromatography, and the yield was 39%.

[0049] Example 8

[0050] In a 6cm x 3cm x 6cm single-compartment electrolytic cell reactor, acetyl, ammonium acetate was dissolved in buffer solution, the ratio was 1:1.5, the air flow was 20 mL / min, the reaction was carried out at a reaction temperature of 50°C, Cu-Mg catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine was obtained, which was quantitatively analyzed by liquid chromatography, and the yield was 39%.

[0051] Example 9

[0052] In a 6cm x 3cm x 6cm single-compartment electrolytic cell reactor, acetyl, ammonium acetate was dissolved in buffer solution, the ratio was 1:1.5, the air flow was 20 mL / min, the reaction was carried out at a reaction temperature of 50°C, Cu-Mg catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine was obtained, which was quantitatively analyzed by liquid chromatography, and the yield was 39%.

[0053] Example 10

[0054] In a 6cm x 3cm x 6cm single-compartment electrolytic cell reactor, acetyl, ammonium acetate was dissolved in buffer solution, the ratio was 1:1.5, the air flow was 20 mL / min, the reaction was carried out at a reaction temperature of 50°C, Cu-Mg catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine was obtained, which was quantitatively analyzed by liquid chromatography, and the yield was 39%.

[0055] Comparative Example 1

[0056] In a 6cm x 3cm x 6cm single-chamber electrolytic cell reactor, acetyl, ammonium acetate was dissolved in aqueous solution, the ratio was 1:1.2, the air flow was 20 mL / min, the reaction was carried out at a reaction temperature of 40°C, Cu-Zn catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine was obtained, and quantitative analysis was carried out by liquid chromatography, with a yield of 15%.

[0057] Comparative Example 2

[0058] In a 6cm x 3cm x 6cm single-chamber electrolytic cell reactor, acetyl, ammonium acetate was dissolved in a buffer solution, the ratio was 1:1.2, the air flow was 10 mL / min, the reaction was carried out at a reaction temperature of 40°C, Cu-Zn catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine was obtained, and quantitative analysis was carried out by liquid chromatography, with a yield of 41%.

[0059] Comparative Example 3

[0060] In a 6cm x 3cm x 6cm single-chamber electrolytic cell reactor, acetyl, ammonium acetate was dissolved in aqueous solution, the ratio was 1:1.2, the air flow was 20 mL / min, the reaction was carried out at a reaction temperature of 30°C, Cu-Ni catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine was obtained, and quantitative analysis was carried out by liquid chromatography, with a yield of 29%.

[0061] Comparative Example 4

[0062] In a 6cm x 3cm x 6cm single-chamber electrolytic cell reactor, acetyl, ammonium acetate was dissolved in aqueous solution, the ratio was 1:1.2, the air flow was 20 mL / min, the reaction was carried out at a reaction temperature of 40°C, Cu mesh catalyst and a voltage of 1.4V, and after 6h of reaction, the 2,3,5,6-tetramethylpyrazine was obtained, and quantitative analysis was carried out by liquid chromatography, with a yield of 25%.

[0063] Results analysis:

[0064] Compared with Examples 2, 3 and 4, increasing the proportion of ammonium acetate and improving the reaction temperature can appropriately increase the yield of tetramethylpyrazine; compared with Example 5, replacing the ammonium salt with a mixed solution of ammonium acetate and ammonium phosphate is beneficial to improving the yield of tetramethylpyrazine; compared with Examples 6 and 8, Cu-Ni has better tetramethylpyrazine yield than Cu-Mg and Cu-Zn catalysts, which may be due to its good dehydrogenation ability; compared with Example 9, increasing the oxygen flow helps to improve the yield of tetramethylpyrazine.

[0065] Compared with Example 1, the yield of tetramethylpyrazine is reduced from 49% to 15% when the buffer solution is replaced by water solution in Comparative Example 1, which indicates the importance of buffer solution; the yield of tetramethylpyrazine is reduced from 49% to 41% when the air flow is reduced from 20 mL / min to 10 mL / min in Comparative Example 2, which indicates that increasing the air oxidation capacity is helpful to improve the yield of tetramethylpyrazine; the yield of tetramethylpyrazine is reduced from 49% to 29% when the reaction temperature is reduced from 40℃ to 30℃ in Comparative Example 3, which indicates that the reaction temperature is helpful to cross the reaction energy barrier; the yield of tetramethylpyrazine is reduced from 49% to 25% when the Cu mesh catalyst is used in Comparative Example 4, which indicates the importance of the second metal for the reaction.

[0066] The embodiments of the present application significantly improve the yield of tetramethylpyrazine by synergistic regulation of reaction temperature, buffer solution, catalyst, air flow, reactant ratio and ammonium salt type, which are far superior to the comparative examples, and realize the electrocatalytic green synthesis of tetramethylpyrazine.

[0067] It should be noted that the above examples are only used to illustrate the technical solutions of the present application and are not limited. Although the present application has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that the technical solutions of the present application can be modified or replaced by equivalents without departing from the spirit and scope of the technical solutions of the present application, which should be covered in the scope of the claims of the present application.

Claims

1. A method for the electrocatalytic synthesis of tetramethylpyrazine, characterized by: The application relates to a method for preparing 2,3,5,6-tetramethylpyrazine. The Cu-based catalyst comprises Cu and a second metal selected from one of Ni, Mg and Zn. The buffer solution is obtained by mixing diammonium hydrogen phosphate solution and ammonium dihydrogen phosphate solution, and the diammonium hydrogen phosphate solution and the ammonium dihydrogen phosphate solution have a concentration of 0.2 mol / L. The molar ratio of Cu to the second metal in the Cu-based catalyst is 10:

1.

2. The electrocatalytic synthesis of tetramethylpyrazine according to claim 1, characterized in that: The molar ratio of ethyl glyoxal to the ammonium salt is 1:1.1-2.

3. The electrocatalytic synthesis of tetramethylpyrazine according to claim 1, characterized by: The ammonium salt is one or more of ammonium acetate, ammonium sulfate, ammonium citrate and ammonium phosphate.

4. The electrocatalytic synthesis of tetramethylpyrazine according to claim 3, characterized in that: The ammonium salt is a mixed aqueous solution of ammonium acetate and ammonium phosphate, and the molar ratio of ammonium acetate to ammonium phosphate is 0.1-1:

1.

5. The electrocatalytic synthesis of tetramethylpyrazine according to claim 4, characterized by the fact that: The Cu-based catalyst is prepared by a deposition precipitation method, a Cu mesh is used as a substrate, aqueous solutions of Ni(NO3)2, Mg(NO3)2 and Zn(NO3)2 are used as second metal precursors, and a precipitant sodium hydroxide is added to deposit one of Ni, Mg and Zn on the Cu mesh.

6. The electrocatalytic synthesis of tetramethylpyrazine according to claim 1, characterized by: The mesh number of the Cu mesh used in the Cu-based catalyst is 200-600.

7. The electrocatalytic synthesis of tetramethylpyrazine according to claim 6, characterized by the fact that: ​

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