Preparation method and device of quinoxaline compound

Abstract

The invention provides a preparation method and device of quinoxaline compounds, and belongs to the technical field of quinoxaline compound synthesis. The preparation method of the quinoxaline compound comprises the following steps: mixing a substituted 1, 2-dicarbonyl compound and a substituted o-phenylenediamine compound to obtain a mixed raw material; and blowing the mixed raw material into a reaction chamber for reaction to obtain the quinoxaline compound, and finally, carrying out vacuum drying on the quinoxaline compound. High-speed spiral gas is formed in the reaction cavity through high-pressure carrier gas, and the mixed raw materials react in the high-speed spiral gas flow. The preparation process provided by the invention has the advantages of low equipment investment, simple process, high reaction speed, high yield, no need of participation of any solvent and catalyst, environmental friendliness and capability of reducing the production cost.

Description

Technical Field

[0001] The present invention relates to the technical field of quinoxaline compound synthesis, and in particular to a method and device for preparing quinoxaline compounds. Background Art

[0002] Quinoxaline is an important nitrogen-containing heterocyclic compound, which is a ring complex composed of a benzene ring and a pyrazine ring. Differently substituted quinoxaline and its derivatives embedded with various functional groups are important biological inhibitors. They have many significant pharmacological effects, such as anti-tumor, antibacterial, anti-inflammatory, weight loss and treatment of diabetes. At the same time, this type of compound can also be used in dyes and fluorescent probes.

[0003] The traditional synthesis method of quinoxaline compounds is to heat and reflux 1,2-dicarbonyl compounds and aromatic-diamine compounds in an ethanol or acetic acid system for 12 hours to achieve condensation of amino and aldehyde groups. The reaction yield is 34%-85%. At the same time, a large amount of organic solvent is consumed, the operation time is long, the reaction requires heating, and there is a certain degree of pollution to the environment, which is not suitable for industrial-scale production.

[0004] Therefore, it is of great practical significance to provide a method for preparing quinoxaline compounds with low energy consumption, high yield and high efficiency. Summary of the invention

[0005] The object of the present invention is to provide a method and device for preparing quinoxaline compounds. The method for preparing quinoxaline compounds of the present invention has the advantages of fast reaction speed, high yield, high product purity, low energy consumption, high efficiency, strong practicality, etc. At the same time, the equipment investment adopted in the preparation method is small, the production requirements are low, the process is simple, and it is very easy to realize industrial production.

[0006] In order to achieve the above-mentioned object of the invention, the present invention provides the following technical solutions:

[0007] The present invention provides a method for preparing a quinoxaline compound, comprising the following steps:

[0008] Mixing a substituted 1,2-dicarbonyl compound and a substituted o-phenylenediamine compound to obtain a mixed raw material;

[0009] Blowing the mixed raw materials into a reaction chamber for reaction to obtain a quinoxaline compound;

[0010] vacuum drying the quinoxaline compound;

[0011] The reaction chamber is filled with high-pressure carrier gas to form a high-speed spiral airflow inside;

[0012] The pressure of the high-pressure carrier gas is 0.2-1.5 MPa.

[0013] Preferably, the feed gas pressure of the mixed raw material blown into the reaction chamber is 0.3MPa to 1.6MPa.

[0014] Preferably, the substituted 1,2-dicarbonyl compound is one of benzil, acenaphthenequinone or phenanthrenequinone.

[0015] Preferably, the substituted o-phenylenediamine compound is one of o-phenylenediamine and 4-chloro-o-phenylenediamine.

[0016] Preferably, the molar ratio of the substituted 1,2-dicarbonyl compound to the substituted o-phenylenediamine compound is 1:1.

[0017] Preferably, the vacuum drying temperature is ≤50°C, and the vacuum drying time is 5 hours.

[0018] The present invention also provides a device for the preparation method of the quinoxaline compound, comprising a reaction chamber 4 and a collecting tank 6, wherein the collecting tank 6 is located below the reaction chamber 4 and connected to the lower outlet of the reaction chamber 4, a bag collector 1 is connected to the upper outlet of the reaction chamber 4, a dust collecting bag 3 is arranged inside the bag collector 1, an air flow outlet 2 is arranged on the upper side of the bag collector 1, a main air intake pipe 9 is connected to the right side of the air distributor 8, a feeder 7 is arranged above, and two air distribution ports are provided behind the air distributor 8, which are respectively connected to the carrier gas pipeline port 10 and the feed gas pipeline port 11 on the reaction chamber 4 through pipelines.

[0019] Preferably, four inclined nozzles 401 are evenly distributed on the annular wall of the reaction chamber, a high-speed spiral airflow 403 is generated by high-pressure carrier gas, a feed inlet 402 of reactants is provided below the nozzle 1, and an outlet 404 is provided below the annular wall of the reaction chamber.

[0020] Compared with the prior art, the technical solution of the present invention has the following beneficial effects:

[0021] (1) The present invention utilizes high-speed spiral airflow to drive the mixed powder of substituted 1,2-dicarbonyl compounds and substituted o-phenylenediamine compounds to move at high speed, and violent friction and collision occur between the reactant particles, and the particle size is rapidly refined to a great extent, and the substituted 1,2-dicarbonyl compounds and substituted o-phenylenediamine compounds are fully dispersed and contacted, and the reaction activity is enhanced. Under the action of mechanical energy, a chemical reaction occurs quickly to transform into a quinoxaline compound. Compared with the traditional preparation method, the present invention has small equipment investment, low production requirements, simple process, and is very easy to realize industrial production. It has the advantages of fast reaction speed, high yield, high product purity, low energy consumption, high efficiency, and strong practicality.

[0022] (2) The preparation process of the present invention does not require the participation of any solvent or catalyst, which is not only environmentally friendly, but also can reduce production costs, directly obtain analytically pure products without further purification, and greatly simplify the process. BRIEF DESCRIPTION OF THE DRAWINGS

[0023] Figure 1 It is a schematic diagram of the structure of the reaction device used in the present invention; it includes: 1-bag collector, 2-air flow outlet, 3-dust collecting bag, 4-reaction chamber, 5-feeding funnel, 6-collecting tank, 7-feeder, 8-gas distributor, 9-main air inlet pipe, 10-carrier gas pipeline port, 11-feeding gas pipeline port;

[0024] Figure 2 Schematic diagram of the reaction chamber structure of the present invention; including: 401-nozzle, 402-feed port, 403-high-speed spiral airflow, 404-outlet;

[0025] Figure 3 is the H NMR spectrum of the quinoxaline compound prepared in Example 1 of the present invention;

[0026] Figure 4 is the H NMR spectrum of the quinoxaline compound prepared in Example 2 of the present invention;

[0027] Figure 5 is the H NMR spectrum of the quinoxaline compound prepared in Example 3 of the present invention;

[0028] Figure 6 is the H NMR spectrum of the quinoxaline compound prepared in Example 4 of the present invention;

[0029] Figure 7 is the H NMR spectrum of the quinoxaline compound prepared in Example 5 of the present invention;

[0030] Figure 8 This is a schematic diagram of the structural formula of the reaction for preparing quinoxaline compounds in Example 1 of the present invention. DETAILED DESCRIPTION

[0031] The present invention provides a method for preparing a quinoxaline compound, comprising the following steps:

[0032] Mixing a substituted 1,2-dicarbonyl compound and a substituted o-phenylenediamine compound to obtain a mixed raw material;

[0033] Blowing the mixed raw materials into a reaction chamber for reaction to obtain a quinoxaline compound;

[0034] vacuum drying the quinoxaline compound;

[0035] The reaction chamber is filled with high-pressure carrier gas to form a high-speed spiral airflow inside;

[0036] The pressure of the high-pressure carrier gas is 0.2-1.5 MPa.

[0037] In the present invention, unless otherwise specified, the required raw materials for preparation are all commercially available products well known to those skilled in the art.

[0038] In the present invention, the feed gas pressure of the mixed raw material blown into the reaction chamber is preferably 0.3 MPa to 1.6 MPa.

[0039] In the present invention, the substituted 1,2-dicarbonyl compound is preferably one of benzil, acenaphthenequinone or phenanthrenequinone, and more preferably one of benzil or acenaphthenequinone;

[0040] In the present invention, the substituted o-phenylenediamine compound is preferably one of o-phenylenediamine and 4-chloro-o-phenylenediamine, and is more preferably o-phenylenediamine.

[0041] In the present invention, the molar ratio of the substituted 1,2-dicarbonyl compound to the substituted o-phenylenediamine compound is 1:1.

[0042] In the present invention, the vacuum drying temperature is ≤50°C, and the vacuum drying time is 5h.

[0043] The present invention also provides a device for the preparation method of the quinoxaline compounds, including a reaction chamber 4 and a collecting tank 6, wherein the collecting tank 6 is located below the reaction chamber 4 and connected to the lower end outlet, a bag collector 1 is connected to the upper end outlet of the reaction chamber 4, a dust collecting bag 3 is arranged inside, an air flow outlet 2 is arranged on the upper end side of the bag collector 1, a total air intake pipe 9 is connected to the left side of the air path distributor 8, a feeder 7 is arranged above, the air path distributor 8 distributes the total intake air into feed gas and high-pressure carrier gas respectively, and is connected to the reaction chamber through a pneumatic tube, and a feed funnel 5 is arranged on the feed gas pipeline.

[0044] Preferably, four inclined nozzles 401 are evenly distributed on the annular wall of the reaction chamber, and the high-pressure carrier gas generates a high-speed spiral airflow 403 through the four nozzles 401. The reactants enter the high-speed spiral airflow through the feed port 402, and the fine particle products are classified by the high-speed spiral airflow and fall into the collection tank 6 from the outlet 404.

[0045] In the present invention, the gas path distributor 8 is first adjusted to adjust the carrier gas pressure to the target pressure, and then the feed gas pressure is adjusted to form a negative pressure at the feed port; then the reactants are simply mixed in a mortar, and the mixed material is added to the feed funnel 5 through the feeder 7; the high-pressure carrier gas enters the four nozzles 401 of the reaction chamber through the high-pressure gas pipeline, and then enters the reaction chamber to form a high-speed spiral airflow 403, and the feed gas pressurized by the feed gas pipeline sprays the reactants in the feed funnel 5 into the reaction chamber 4 from the feed port 402. The reactant particles move at high speed under the drive of the high-speed spiral airflow to react. After the reaction is completed, the fine particle product is subjected to the centripetal force in the spiral airflow and is classified and falls into the collection tank 6 through the outlet 404, and the gas is discharged through the airflow outlet, and a small amount of powder is brought into the dust collecting bag 3 by the gas.

[0046] The technical solutions provided by the present invention are described in detail below in conjunction with the embodiments, but they should not be construed as limiting the protection scope of the present invention.

[0047] Example 1

[0048] (1) Accurately weigh 1.32 g (6 mmol) of benzil and 0.89 g (6 mmol) of 4-chloro-o-phenylenediamine, mix them and set aside;

[0049] (2) Open the main gas source and adjust the gas distributor 8 so that the feed gas pressure is 1.1 MPa and the high-pressure carrier gas pressure is 1.0 MPa, and the high-pressure carrier gas forms a high-speed spiral airflow in the reaction chamber;

[0050] (3) The mixed raw materials are added to the feed funnel 5 and brought into the reaction chamber 4 by the feed gas. The reactant particles move at high speed under the drive of the high-speed spiral airflow. The particles rub and collide with each other, and the particle size is greatly refined, the reaction activity is enhanced, and the chemical reaction is quickly completed under the action of mechanical energy to generate quinoxaline compounds. The fine particle product is affected by the centripetal force of the spiral airflow and is continuously graded and falls into the collection tank 6. The reaction is completed within 3 minutes. After completion, the collection tank 6 is opened, and the white solid scraped out from the collection tank is the quinoxaline compound product. It is vacuum dried at a temperature of 30° C. for 5 hours and then weighed to obtain a quinoxaline compound product with a yield of 98%;

[0051] The structural diagram of the above reaction is as follows:

[0052]

[0053] Example 2

[0054] (1) Accurately weigh 1.32 g (6 mmol) of benzil and 0.68 g (6 mmol) of o-phenylenediamine, mix them and set aside;

[0055] (2) Open the main gas source and adjust the gas distributor 8 so that the feed gas pressure is 1.2 MPa and the high-pressure carrier gas pressure is 1.1 MPa, and the high-pressure carrier gas forms a high-speed spiral airflow in the reaction chamber;

[0056] (3) The mixed raw materials are added to the feed funnel 5 and brought into the reaction chamber 4 by the feed gas. The reactant particles move at high speed under the drive of the high-speed spiral airflow. The particles rub and collide with each other, and the particle size is greatly refined, the reaction activity is enhanced, and the chemical reaction is quickly completed under the action of mechanical energy to generate quinoxaline compounds. The fine particle product is affected by the centripetal force of the spiral airflow and is continuously graded and falls into the collection tank 6. The reaction is completed within 3 minutes. After completion, the collection tank 6 is opened, and the white solid scraped out from the collection tank is the quinoxaline compound product. It is vacuum dried at a temperature of 30° C. for 5 hours and then weighed to obtain a quinoxaline compound product with a yield of 95%;

[0057] The structural diagram of the above reaction is:

[0058]

[0059] Example 3

[0060] (1) Accurately weigh 1.09 g (6 mmol) of acenaphthenequinone and 0.68 g (6 mmol) of o-phenylenediamine, mix them and set aside;

[0061] (2) Open the main gas source and adjust the gas distributor 8 so that the feed gas pressure is 1.2 MPa and the high-pressure carrier gas pressure is 1.1 MPa, and the high-pressure carrier gas forms a high-speed spiral airflow in the reaction chamber;

[0062] (3) The mixed raw materials are added to the feed funnel 5 and brought into the reaction chamber 4 by the feed gas. The reactant particles move at high speed under the drive of the high-speed spiral airflow. The particles rub and collide with each other, the particle size is greatly refined, the reaction activity is enhanced, and the chemical reaction is quickly completed under the action of mechanical energy to generate quinoxaline compounds. The fine particle products are affected by the centripetal force of the spiral airflow and are continuously graded and fall into the collection tank 6. The reaction is completed within 3 minutes. After completion, the collection tank 6 is opened, and the white solid scraped out from the collection tank is the quinoxaline compound product. After vacuum drying at 30° C. for 5 hours, it is weighed to obtain a quinoxaline compound product with a yield of 98%.

[0063] The structural diagram of the above reaction is as follows:

[0064]

[0065] Example 4

[0066] (1) Accurately weigh 1.09 g (6 mmol) of acenaphthenequinone and 0.89 g (6 mmol) of 4-chloro-o-phenylenediamine, mix them and set aside;

[0067] (2) Open the total gas source and adjust the gas distributor 8 so that the feed gas pressure is 1.3 MPa and the high-pressure carrier gas pressure is 1.2 MPa, and the high-pressure carrier gas forms a high-speed spiral airflow in the reaction chamber;

[0068] (3) The mixed raw materials are added to the feed funnel 5 and brought into the reaction chamber 4 by the feed gas. The reactant particles move at high speed under the drive of the high-speed spiral airflow. The particles rub and collide with each other, and the particle size is greatly refined, the reaction activity is enhanced, and the chemical reaction is quickly completed under the action of mechanical energy to generate quinoxaline compounds. The fine particle product is affected by the centripetal force of the spiral airflow and is continuously graded and falls into the collection tank 6. The reaction is completed within 3 minutes. After completion, the collection tank 6 is opened, and the white solid scraped out from the collection tank is the quinoxaline compound product. It is vacuum dried at a temperature of 30° C. for 5 hours and then weighed to obtain a quinoxaline compound product with a yield of 98%;

[0069] The above reaction structural diagram is as follows:

[0070]

[0071] Example 5

[0072] (1) Accurately weigh 1.25 g (6 mmol) of phenanthrenequinone and 0.68 g (6 mmol) of o-phenylenediamine, mix them and set aside;

[0073] (2) Open the total gas source and adjust the gas distributor 8 so that the feed gas pressure is 1.0 MPa and the high-pressure carrier gas pressure is 0.8 MPa, and the high-pressure carrier gas forms a high-speed spiral airflow in the reaction chamber;

[0074] (3) The mixed raw materials are added to the feed funnel 5 and brought into the reaction chamber 4 by the feed gas. The reactant particles move at high speed under the drive of the high-speed spiral airflow. The particles rub and collide with each other, and the particle size is greatly refined, the reaction activity is enhanced, and the chemical reaction is quickly completed under the action of mechanical energy to generate quinoxaline compounds. The fine particle product is affected by the centripetal force of the spiral airflow and is continuously graded and falls into the collection tank 6. The reaction is completed within 3 minutes. After completion, the collection tank 6 is opened, and the white solid scraped out from the collection tank is the quinoxaline compound product. It is vacuum dried at a temperature of 30° C. for 5 hours and then weighed to obtain a quinoxaline compound product with a yield of 98%;

[0075] The above reaction structural diagram is as follows:

[0076]

[0077] test

[0078] (1) The structural characterization of the quinoxaline compound product obtained in Example 1 is as follows: 1 HNMR(600MHz,Chloroform-d)δ8.24–8.17(m,2H),7.82–7.76(m,2H),7.57–7.50(m,4H),7.41–7.31(m,6H), Figure 3 is the H NMR spectrum of the quinoxaline compound product;

[0079] (2) The structural characterization of the quinoxaline compound product obtained in Example 2 is as follows: 1 HNMR(600MHz,Chloroform-d)δ8.18(d,J=2.3Hz,1H),8.11(d,J=8.8Hz,1H),7.71(dd,J=8.9,2.3Hz,1H),7.53–7.49(m,4H),7.41–7.32(m,6H), Figure 4 is the H NMR spectrum of the quinoxaline compound product;

[0080] (3) The structural characterization of the quinoxaline compound product obtained in Example 3 is as follows: 1 HNMR(600MHz,Chloroform-d)δ8.44(d,J=7.1Hz,2H),8.26–8.20(m,2H),8.11(d,J=8.2Hz,2H),7.85(dd,J=8.2,6.9Hz,2H),7.80–7.74(m,2H), Figure 5 is the H NMR spectrum of the quinoxaline compound product;

[0081] (4) The structural characterization of the quinoxaline compound product obtained in Example 4 is as follows: 1 HNMR(600MHz,Chloroform-d)δ8.39(t,J=6.5Hz,2H),8.18(d,J=2.3Hz,1H),8.14–8.09(m,3H),7.87–7.81(m,2H),7.68(dd,J=8.8,2.4Hz,1H), Figure 6 is the H NMR spectrum of the quinoxaline compound product;

[0082] (5) The structural characterization of the quinoxaline compound product obtained in Example 5 is as follows: 1HNMR(600MHz,Chloroform-d)δ9.40(dd,J=7.9,1.5Hz,2H),8.55(dd,J=8.0,1.2Hz ,2H),8.35–8.28(m,2H),7.88–7.81(m,2H),7.81–7.76(m,2H),7.76–7.71(m,2H), Figure 7 This is the H NMR spectrum of the quinoxaline compound product.

[0083] The above is only a preferred embodiment of the present invention. It should be pointed out that for ordinary technicians in this technical field, several improvements and modifications can be made without departing from the principle of the present invention. These improvements and modifications should also be regarded as the scope of protection of the present invention.

Claims

1. A method for preparing a quinoxaline compound, It is characterized in that The following steps are involved: Mixing a substituted 1,2-dicarbonyl compound and a substituted o-phenylenediamine compound to obtain a mixed raw material; Blowing the mixed raw materials into a reaction chamber for reaction to obtain a quinoxaline compound; vacuum drying the quinoxaline compound; The reaction chamber is filled with high-pressure carrier gas to form a high-speed spiral airflow inside; The pressure of the high-pressure carrier gas is 0.2-1.5 MPa.

2. The method for preparing the quinoxaline compound according to claim 1, It is characterized in that The feed gas pressure of the mixed raw material blown into the reaction chamber is 0.3MPa to 1.6MPa.

3. The method for preparing the quinoxaline compound according to claim 1, It is characterized in that The substituted 1,2-dicarbonyl compound is one of benzil, acenaphthenequinone or phenanthrenequinone.

4. The method for preparing the quinoxaline compound according to claim 1, It is characterized in that The substituted o-phenylenediamine compound is one of o-phenylenediamine and 4-chloro-o-phenylenediamine.

5. The method for preparing the quinoxaline compound according to claim 1, It is characterized in that The molar ratio of the substituted 1,2-dicarbonyl compound to the substituted o-phenylenediamine compound is 1:

1.

6. The method for preparing the quinoxaline compound according to claim 1, It is characterized in that The vacuum drying temperature is ≤50°C, and the vacuum drying time is 5h.

7. A device for preparing the quinoxaline compound according to any one of claims 1 to 6, It is characterized in that The invention comprises a reaction chamber (4) and a collecting tank (6), wherein the collecting tank (6) is located below the reaction chamber (4) and connected to the lower outlet of the reaction chamber (4); a bag collector (1) is connected to the upper outlet of the reaction chamber (4) and is provided with a dust collecting bag (3); an air flow outlet (2) is provided on the upper side of the bag collector (1); a gas path distributor (8) is connected to the main air inlet pipe (9) on the right side, and a feeder (7) is provided above; and two gas path distribution ports are provided behind the gas path distributor (8), which are respectively connected to a carrier gas pipeline port (10) and a feed gas pipeline port (11) on the reaction chamber (4) through pipelines.

8. The device for preparing the quinoxaline compound according to claim 7, It is characterized in that Four nozzles (401) arranged obliquely are evenly distributed on the annular wall of the reaction chamber (4), a high-speed spiral airflow (403) is generated by a high-pressure carrier gas, a feed inlet (402) of a reactant is provided below the nozzle (401), and an outlet (404) is provided below the annular wall of the reaction chamber.

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