A preparation method of phenothiazine

Abstract

The present invention belongs to the field of compound synthesis technology, and specifically discloses a preparation method of phenothiazine. The preparation method provided by the present invention adds bis(2-bromophenyl)amine, potassium thioacetate and potassium carbonate to an organic solvent, and then adds cuprous iodide to make a mixed solution; the mixed solution is heated to react to prepare phenothiazine. The preparation method of phenothiazine provided by the present invention is simple to operate, easy to post-process, cheap raw materials, and easy to industrialize.

Description

Technical Field

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

[0002] Phenothiazine and its derivatives are an important class of organic compounds with broad application prospects. For example, phenothiazine compounds can be used as luminescent materials, dyes, and in the preparation of anti-tumor drugs.

[0003] Currently, there are numerous reports on the preparation of phenothiazine compounds, primarily using diphenylamine and its derivatives with sulfur in the presence of a catalyst. Existing catalysts primarily include elemental iodine, aluminum chloride, and activated clay. These reported methods for synthesizing phenothiazine compounds suffer from high energy consumption and production costs.

[0004] In order to improve the applicability of the synthesis of phenothiazine compounds and make them easier to industrialize, people have been looking for more efficient and convenient synthesis methods. The present invention aims to provide a new method for preparing phenothiazine. Summary of the Invention

[0005] The main technical problem solved by the present invention is to provide a preparation method of phenothiazine, which has the advantages of simple operation and easy industrial production.

[0006] In order to solve the above technical problems, the present invention adopts the following technical solutions:

[0007] A method for preparing phenothiazine, comprising the steps of:

[0008] (1) adding bis(2-bromophenyl)amine, potassium thioacetate, and potassium carbonate to an organic solvent, and then adding cuprous iodide (CuI) to prepare a mixed solution;

[0009] (2) heating the mixed solution to react and obtain phenothiazine.

[0010] The reaction formula of the phenothiazine preparation method provided by the present invention is:

[0011]

[0012] As an embodiment of the present invention, both step (1) and step (2) are carried out under the protection of an inert gas, and preferably the inert gas is nitrogen.

[0013] As an embodiment of the present invention, in step (1), the molar ratio of the potassium thioacetate to the bis(2-bromophenyl)amine is (1.0-1.2):1, preferably the molar ratio is (1.1-1.2):1.

[0014] As an embodiment of the present invention, in step (1), the molar ratio of the potassium carbonate to the bis(2-bromophenyl)amine is (2.0-3.0):1.

[0015] As an embodiment of the present invention, in step (1), the molar ratio of the cuprous iodide to the bis(2-bromophenyl)amine is (0.01-0.20):1, preferably the molar ratio is (0.08-0.12):1.

[0016] As an embodiment of the present invention, in step (1), the organic solvent is DMF (N,N-dimethylformamide), preferably anhydrous DMF.

[0017] As an embodiment of the present invention, in step (2), the reaction temperature of the reaction is 100-150°C, preferably 120-140°C.

[0018] As an embodiment of the present invention, in step (2), the reaction time of the reaction is 10-15 hours.

[0019] As one embodiment of the present invention, the method for preparing phenothiazine provided by the present invention further comprises post-processing the reaction solution obtained in step (2), wherein the post-processing method comprises:

[0020] The reaction solution obtained in step (2) is cooled to -5 to 5°C, water is added, and then crystallized at -5 to 5°C; then filtered, and the obtained solid is dried to obtain the phenothiazine product.

[0021] Preferably, the post-treatment method comprises: cooling the reaction solution obtained in step (2) to 0°C, adding water, and then crystallizing at 0°C; then filtering and drying the obtained solid to obtain the phenothiazine product.

[0022] Preferably, during post-treatment, the volume of water added is 3 times or more of the volume of the reaction solution, preferably 3 to 6 times.

[0023] As a preferred embodiment of the present invention, in step (1), the molar ratio of the potassium thioacetate to the bis(2-bromophenyl)amine is 1.1:1, the molar ratio of the potassium carbonate to the bis(2-bromophenyl)amine is 2.5:1; and the molar ratio of the cuprous iodide to the bis(2-bromophenyl)amine is 0.10:1.

[0024] The present invention also provides a phenothiazine product prepared by the method of the present invention.

[0025] The phenothiazine preparation method provided by the present invention has simple reaction operation, simple post-processing, and cheap and easily available raw materials, and is therefore easy to industrialize. BRIEF DESCRIPTION OF THE DRAWINGS

[0026] Figure 1 This is the H NMR spectrum of the phenothiazine product obtained in Example 1 of the present invention. DETAILED DESCRIPTION

[0027] The technical solution of the present invention is described in detail below through examples.

[0028] The raw materials used in the following examples were purchased unless otherwise specified.

[0029] Example 1

[0030] This embodiment provides a method for preparing phenothiazine, and the preparation steps are as follows:

[0031] Under nitrogen, bis(2-bromophenyl)amine (32.7 g, 0.1 mol), potassium thioacetate (12.5 g, 0.11 mol), and potassium carbonate (34.5 g, 0.25 mol) were added to 400 mL of anhydrous DMF, followed by cuprous iodide (1.9 g, 0.01 mol). The mixture was then stirred and heated to 130°C for 12 hours. TLC confirmed the reaction was complete.

[0032] The reaction solution was cooled to 0°C, and then 2000 mL of water was added and kept at 0°C for 10 hours for crystallization. Filter, collect the filter cake and dry to obtain 18.0 g of phenothiazine with a purity of 96%. The H NMR spectrum of the target compound phenothiazine is shown in Figure 1 shown.

[0033] Example 2

[0034] This embodiment provides a method for preparing phenothiazine, and the preparation steps are as follows:

[0035] Under nitrogen, bis(2-bromophenyl)amine (32.7 g, 0.1 mol), potassium thioacetate (12.5 g, 0.11 mol), and potassium carbonate (34.5 g, 0.25 mol) were added to 400 mL of anhydrous DMF, followed by cuprous iodide (1.9 g, 0.01 mol). The mixture was then stirred and heated to 120°C for 14 hours. TLC confirmed the reaction was complete.

[0036] The resulting reaction solution was cooled to 0°C, and then 2000 mL of water was added and kept at 0°C for crystallization for 10 hours. The solution was filtered, and the filter cake was collected and dried to obtain 17.8 g of phenothiazine with a purity of 97%.

[0037] Example 3

[0038] This embodiment provides a method for preparing phenothiazine, and the preparation steps are as follows:

[0039] Under nitrogen, bis(2-bromophenyl)amine (32.7 g, 0.1 mol), potassium thioacetate (12.5 g, 0.11 mol), and potassium carbonate (34.5 g, 0.25 mol) were added to 400 mL of anhydrous DMF, followed by cuprous iodide (1.9 g, 0.01 mol). The mixture was then stirred and heated to 150°C for 10 hours. TLC confirmed the reaction was complete.

[0040] The resulting reaction solution was cooled to 0°C, and then 2000 mL of water was added and kept at 0°C for crystallization for 10 hours. The solution was filtered, and the filter cake was collected and dried to obtain 17.1 g of phenothiazine with a purity of 95%.

[0041] Example 4

[0042] This embodiment provides a method for preparing phenothiazine, and the preparation steps are as follows:

[0043] Under nitrogen, bis(2-bromophenyl)amine (32.7 g, 0.1 mol), potassium thioacetate (11.4 g, 0.1 mol), and potassium carbonate (34.5 g, 0.25 mol) were added to 400 mL of anhydrous DMF, followed by cuprous iodide (1.9 g, 0.01 mol). The mixture was then stirred and heated to 130°C for 12 hours. TLC confirmed the reaction was complete.

[0044] The resulting reaction solution was cooled to 0°C, and then 2000 mL of water was added and kept at 0°C for 10 hours for crystallization. The solution was filtered, and the filter cake was collected and dried to obtain 15.3 g of phenothiazine with a purity of 96%.

[0045] Example 5

[0046] This embodiment provides a method for preparing phenothiazine, and the preparation steps are as follows:

[0047] Under nitrogen, bis(2-bromophenyl)amine (32.7 g, 0.1 mol), potassium thioacetate (13.7 g, 0.12 mol), and potassium carbonate (34.5 g, 0.25 mol) were added to 400 mL of anhydrous DMF, followed by cuprous iodide (1.9 g, 0.01 mol). The mixture was then stirred and heated to 130°C for 12 hours. TLC confirmed the reaction was complete.

[0048] The resulting reaction solution was cooled to 0°C, and then 2000 mL of water was added and kept at 0°C for crystallization for 10 hours. The solution was filtered, and the filter cake was collected and dried to obtain 17.9 g of phenothiazine with a purity of 96%.

[0049] Example 6

[0050] This embodiment provides a method for preparing phenothiazine, and the preparation steps are as follows:

[0051] Under nitrogen, bis(2-bromophenyl)amine (32.7 g, 0.1 mol), potassium thioacetate (12.5 g, 0.11 mol), and potassium carbonate (34.5 g, 0.25 mol) were added to 400 mL of anhydrous DMF, followed by cuprous iodide (1.9 g, 0.01 mol). The mixture was then stirred and heated to 130°C for 12 hours. TLC confirmed the reaction was complete.

[0052] The resulting reaction solution was cooled to 0°C, and then 800 mL of water was added and kept at 0°C for 10 hours for crystallization. The solution was filtered, and the filter cake was collected and dried to obtain 16.2 g of phenothiazine with a purity of 85%.

[0053] Example 7

[0054] This embodiment provides a method for preparing phenothiazine, and the preparation steps are as follows:

[0055] Under nitrogen, bis(2-bromophenyl)amine (327 g, 1.0 mol), potassium thioacetate (125.4 g, 1.1 mol), and potassium carbonate (345 g, 2.5 mol) were added to 3 L of anhydrous DMF, followed by cuprous iodide (19 g, 0.1 mol). The mixture was then stirred and heated to 130°C for 15 hours. TLC confirmed the reaction was complete.

[0056] The resulting reaction solution was cooled to 0°C, and then 12 L of water was added and kept at 0°C for 10 hours for crystallization. The solution was filtered, and the filter cake was collected and dried to obtain 181 g of phenothiazine with a purity of 95%.

[0057] The above descriptions are merely embodiments of the present invention and are not intended to limit the patent scope of the present invention. Any equivalent transformations made using the contents of the present invention specification, or any direct or indirect application in other related technical fields, are included in the patent protection scope of the present invention.

Claims

1. A method for preparing phenothiazine, characterized in that: The method comprises the steps of: (1) Add bis(2-bromophenyl)amine, potassium thioacetate and potassium carbonate to an organic solvent, and then add cuprous iodide to prepare a mixed solution; (2) The mixed solution is heated to react to obtain phenothiazine.

2. The method according to claim 1, characterized in that Both steps (1) and (2) are carried out under the protection of inert gas.

3. The method according to claim 2, characterized in that The inert gas is nitrogen.

4. The method according to claim 1 or 2, characterized in that In step (1), the molar ratio of the potassium thioacetate to the bis(2-bromophenyl)amine is (1.0-1.2):

1.

5. The method according to claim 4, characterized in that In step (1), the molar ratio of the potassium carbonate to the bis(2-bromophenyl)amine is (2.0-3.0):

1.

6. The method according to claim 5, characterized in that In step (1), the molar ratio of the cuprous iodide to the bis(2-bromophenyl)amine is (0.01-0.20):

1.

7. The method according to claim 6, characterized in that In step (1), the organic solvent is DMF.

8. The method according to claim 1, characterized in that In step (2), the reaction temperature is 100-150° C.; and / or the reaction time is 10-15 hours.

9. The method according to claim 1, characterized in that The method further comprises post-processing the reaction solution obtained in step (2), wherein the post-processing method comprises: The reaction solution obtained in step (2) is cooled to -5 to 5°C, water is added, and then crystallized at -5 to 5°C; then filtered, and the obtained solid is dried to obtain the phenothiazine product.

10. The method according to claim 1, characterized in that In step (1), the molar ratio of the potassium thioacetate to the bis(2-bromophenyl)amine is 1.1:1, and / or the molar ratio of the potassium carbonate to the bis(2-bromophenyl)amine is 2.5:1; and / or the molar ratio of the cuprous iodide to the bis(2-bromophenyl)amine is 0.10:1.

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