Synthesis method of 1, 6-dichlorophenazine

Abstract

The invention relates to a synthesis method of 1, 6-dichlorophenazine. The synthesis method of 1, 6-dichlorophenazine comprises the following steps: weighing raw materials o-chloroaniline and nickel chloride; the preparation method comprises the following steps: adding raw materials o-chloroaniline, nickel chloride and a solvent DMF into a three-neck bottle, and stirring; raising the temperature of the system to 160-170 DEG C, and carrying out stirring reaction, and after the reaction, cooling and filtering to obtain a yellow solid, namely the 1, 6-dichlorophenazine. Compared with the prior art, the method has the advantages that the o-chloroaniline is used as the raw material, under the heating conditions of the high-boiling-point solvent and the catalyst nickel chloride, the 1, 6-dichlorophenazine is obtained through ring closing, the yield is high, few reaction byproducts are generated, the product purity is high, industrial production is easy to achieve, operation is easy, the reaction temperature is not high, control is easy, and environment friendliness is achieved.

Description

Technical Field

[0001] The invention relates to the technical field of organic synthesis, and in particular to a method for synthesizing 1,6-dichlorophenazine. Background Art

[0002] Phenazine compounds are a large class of antibacterial and anti-tumor active substances in nature. They are fused-ring compounds containing two benzene rings and one pyrazine ring. Phenazine compounds have a wide range of uses, mainly including the following aspects: Medical field: such as antipsychotic drugs chlorpromazine, perphenazine, trifluoperazine, etc., which are used to treat mental illnesses such as schizophrenia, anxiety, depression, etc. by blocking dopamine receptors; the antihistamine drug promethazine has sedative, hypnotic, anti-allergic and antiemetic effects, and can be used to relieve discomfort caused by allergic reactions and motion sickness and seasickness; Agricultural field: some phenazine compounds have antibacterial and antibacterial activities, and have significant inhibitory effects on pathogens such as wheat take-all disease and rice wilt disease. They can be developed as agricultural fungicides to ensure the growth of crops; Dye field: Phenazine is the parent substance of many dyes, such as toluene red, indigo and safranin, which can be used to synthesize a variety of dyes with different colors and properties to meet the needs of textile, printing and dyeing and other industries; Energy field: Aqueous organic liquid flow battery materials: The long-life water-soluble phenazine free radical compound PSPR developed by the West Lake University team has the advantages of high solubility and high stability, showing strong application potential, and can be used as the positive electrode material of aqueous organic liquid flow batteries.

[0003] The early method of synthesizing phenazine and dihydrophenazine is to obtain them by reacting catechol and catechol, but this synthesis method has low yield and many by-products, and cannot be mass-produced. Since phenazine and its derivatives are important fine chemical raw materials, the main synthesis methods at present include 2-amino or nitrodiphenylamine ring-closing reaction, o-phenylenediamine and catechol condensation reaction and other methods for preparation. These methods have the problems of dangerous operation, difficult to control, high reaction temperature, low yield, many by-products, difficult to separate and purify, consumption of organic solvents, large metal dosage, serious environmental pollution, etc. The present invention discloses a method for preparing phenazine compounds from o-chloroaniline as a raw material under the action of a catalyst. This method has the advantages of being environmentally friendly, simple to operate, easy to realize industrial production, and short production cycle. Summary of the invention

[0004] The technical problem to be solved by the present invention is to provide a method for synthesizing 1,6-dichlorophenazine, which can solve the problems of low yield, more by-products, inability to produce on a large scale, dangerous operation, difficult control, high reaction temperature and serious environmental pollution in the prior art synthesis method.

[0005] In order to solve the above technical problems, the technical solution of the present invention is: comprising the following steps: S1. Weigh the raw materials o-chloroaniline and nickel chloride; S2, add raw material o-chloroaniline, nickel chloride and solvent DMF into a three-necked flask and stir; S3, heating the system to 160℃~170℃ and stirring for reaction, the reaction process is: ; S4. After the reaction, cool and filter to obtain a yellow solid, which is 1,6-dichlorophenazine.

[0006] Furthermore, the mass ratio of the raw materials o-chloroaniline and nickel chloride is 100:1-1.5.

[0007] Furthermore, the mass ratio of the added volume of the solvent DMF to o-chloroaniline is 1:1.

[0008] Furthermore, in step S3, the reaction time is 20-22 hours.

[0009] Furthermore, in step S4, the reaction is cooled to 25°C after the reaction.

[0010] The invention has the advantages that: the invention provides a new synthesis method of 1,6-dichlorophenazine, takes o-chloroaniline as a raw material, and performs cyclization to obtain 1,6-dichlorophenazine under heating conditions with a high boiling point solvent and nickel chloride as a catalyst, has high yield, few reaction by-products, high product purity, is easy to realize industrial production, is simple to operate, has a low reaction temperature, is easy to control, and is environmentally friendly. DETAILED DESCRIPTION

[0011] In order to make the purpose, technical scheme and advantages of the present invention more clear, the present invention is further described in detail below in conjunction with specific implementation methods. The following examples can enable technicians in this field to understand the present invention more comprehensively, but the present invention is not limited to the scope of the embodiments.

[0012] This specific implementation adopts the following technical scheme: The synthesis method of 1,6-dichlorophenazine comprises the following steps: S1. Weigh o-chloroaniline and nickel chloride as raw materials, wherein the mass ratio of o-chloroaniline to nickel chloride is 100:1-1.5; S2, adding raw materials o-chloroaniline, nickel chloride and solvent DMF into a three-necked flask, stirring, the mass ratio of the added volume of solvent DMF to o-chloroaniline is 1:1; S3, heating the system to 160℃~170℃ and stirring for reaction, the reaction time is 20-22 hours, the reaction process is: ; S4. After the reaction, cool to 25°C and filter to obtain a yellow solid, which is 1,6-dichlorophenazine.

[0013] Embodiment 1: Add 100 g of o-chloroaniline, 1 g of nickel chloride and 100 mL of DMF into a three-necked flask and stir. Heat the system to 160°C-170°C and stir to react. After reacting for 20 hours, cool to 25°C and filter to obtain 49 g of a yellow solid with an HPLC purity of 98%.

[0014] The structural analysis of the obtained product 1,6-dichlorophenazine is shown in the following table.

[0015] The structural analysis of the obtained product 1,6-dichlorophenazine is shown in the following table: . Comparative Example 1: Add 100 g of o-chloroaniline, 1 g of nickel chloride and 100 mL of xylene into a three-necked flask and stir. Heat the system to 140°C-150°C and stir for reaction. After reacting for 20 hours, cool to 25°C and filter to obtain 18 g of yellow solid with HPLC purity of 97.5%.

[0016] Comparative Example 2: Add 100 g of o-chloroaniline, 1 g of nickel chloride and 100 mL of liquid paraffin into a three-necked flask and stir. Heat the system to 160°C-170°C and stir for reaction. After reacting for 20 hours, cool to 25°C and filter to obtain 15 g of a yellow solid with an HPLC purity of 98%.

[0017] Comparative Example 3: Add 100 g of o-chloroaniline, 2 g of nickel chloride and 100 mL of DMF into a three-necked flask and stir. Heat the system to 160°C-170°C and stir to react. After reacting for 20 hours, cool to 25°C and filter to obtain 45 g of a yellow solid with an HPLC purity of 98%.

[0018] Comparative Example 4: Add 100 g of o-chloroaniline, 0.5 g of nickel chloride and 100 mL of DMF into a three-necked flask and stir. Heat the system to 160°C-170°C and stir to react. After reacting for 20 hours, cool to 25°C and filter to obtain 35 g of a yellow solid with an HPLC purity of 98%.

[0019] It can be seen from the above Example 1 that 1,6-dichlorophenazine is obtained by ring-closing with o-chloroaniline as a raw material under heating conditions with a high boiling point solvent and nickel chloride as a catalyst, with a high yield and high product purity, easy to realize industrial production, simple operation, low reaction temperature, easy control, and environmentally friendly; by comparing Example 1 with Comparative Examples 1-2, it can be seen that when the catalyst nickel chloride is replaced with xylene or liquid paraffin, the yield is significantly reduced, and the purity of the product 1,6-dichlorophenazine in Comparative Example 1 is also reduced; by comparing Example 1 with Comparative Examples 3-4, it can be seen that when the amount of the catalyst nickel chloride is less than 1 gram or exceeds 1.5 grams, that is, when the amount of the catalyst nickel chloride is too low or excessive, the yield is significantly reduced.

[0020] The above shows and describes the basic principles and main features of the present invention and the advantages of the present invention. It should be understood by those skilled in the art that the present invention is not limited to the above embodiments. The above embodiments and descriptions are only for explaining the principles of the present invention. Without departing from the spirit and scope of the present invention, the present invention may have various changes and improvements, which fall within the scope of the present invention to be protected. The scope of protection of the present invention is defined by the attached claims and their equivalents.

Claims

1. A method for synthesizing 1,6-dichlorophenazine, characterized in that: The following steps are involved: S1. Weigh the raw materials o-chloroaniline and nickel chloride; S2, add raw material o-chloroaniline, nickel chloride and solvent DMF into a three-necked flask and stir; S3, heating the system to 160℃~170℃ and stirring for reaction, the reaction process is: ; S4. After the reaction, cool and filter to obtain a yellow solid, which is 1,6-dichlorophenazine.

2. A method for synthesizing 1,6-dichlorophenazine according to claim 1, characterized in that: The mass ratio of the raw materials o-chloroaniline and nickel chloride is 100:1-1.

5.

3. A method for synthesizing 1,6-dichlorophenazine according to claim 1, characterized in that: The mass ratio of the added volume of the solvent DMF to o-chloroaniline is 1:

1.

4. A method for synthesizing 1,6-dichlorophenazine according to claim 1, characterized in that: In step S3, the reaction time is 20-22 hours.

5. A method for synthesizing 1,6-dichlorophenazine according to claim 1, characterized in that: In the step S4, the reaction is followed by cooling to 25°C.

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