CN117777052A - Preparation method of phenothiazine - Google Patents
Preparation method of phenothiazine Download PDFInfo
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- CN117777052A CN117777052A CN202311808293.1A CN202311808293A CN117777052A CN 117777052 A CN117777052 A CN 117777052A CN 202311808293 A CN202311808293 A CN 202311808293A CN 117777052 A CN117777052 A CN 117777052A
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- CN
- China
- Prior art keywords
- phenothiazine
- bromophenyl
- amine
- bis
- molar ratio
- Prior art date
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- 229950000688 phenothiazine Drugs 0.000 title claims abstract description 40
- WJFKNYWRSNBZNX-UHFFFAOYSA-N 10H-phenothiazine Chemical compound C1=CC=C2NC3=CC=CC=C3SC2=C1 WJFKNYWRSNBZNX-UHFFFAOYSA-N 0.000 title claims abstract description 37
- 238000002360 preparation method Methods 0.000 title abstract description 25
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 claims abstract description 28
- BJPIBICIVXDVHC-UHFFFAOYSA-N 2-bromo-n-(2-bromophenyl)aniline Chemical compound BrC1=CC=CC=C1NC1=CC=CC=C1Br BJPIBICIVXDVHC-UHFFFAOYSA-N 0.000 claims abstract description 23
- 229910021595 Copper(I) iodide Inorganic materials 0.000 claims abstract description 16
- LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 claims abstract description 16
- JYWKEVKEKOTYEX-UHFFFAOYSA-N 2,6-dibromo-4-chloroiminocyclohexa-2,5-dien-1-one Chemical compound ClN=C1C=C(Br)C(=O)C(Br)=C1 JYWKEVKEKOTYEX-UHFFFAOYSA-N 0.000 claims abstract description 14
- 229910000027 potassium carbonate Inorganic materials 0.000 claims abstract description 14
- 239000011259 mixed solution Substances 0.000 claims abstract description 6
- 239000003960 organic solvent Substances 0.000 claims abstract description 5
- 238000010438 heat treatment Methods 0.000 claims abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims description 25
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 18
- 238000000034 method Methods 0.000 claims description 17
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 11
- 229910052757 nitrogen Inorganic materials 0.000 claims description 9
- 239000012295 chemical reaction liquid Substances 0.000 claims description 5
- 238000001816 cooling Methods 0.000 claims description 3
- 238000001035 drying Methods 0.000 claims description 3
- 238000001914 filtration Methods 0.000 claims description 3
- 239000007787 solid Substances 0.000 claims description 3
- 239000011261 inert gas Substances 0.000 claims description 2
- 230000035484 reaction time Effects 0.000 claims description 2
- 238000009776 industrial production Methods 0.000 abstract description 4
- 230000015572 biosynthetic process Effects 0.000 abstract description 3
- 150000001875 compounds Chemical class 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000003786 synthesis reaction Methods 0.000 abstract description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000000203 mixture Substances 0.000 description 14
- 239000000243 solution Substances 0.000 description 8
- 238000002425 crystallisation Methods 0.000 description 7
- 230000008025 crystallization Effects 0.000 description 7
- -1 phenothiazine compound Chemical class 0.000 description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- 238000005481 NMR spectroscopy Methods 0.000 description 2
- 239000003054 catalyst Substances 0.000 description 2
- DMBHHRLKUKUOEG-UHFFFAOYSA-N diphenylamine Chemical compound C=1C=CC=CC=1NC1=CC=CC=C1 DMBHHRLKUKUOEG-UHFFFAOYSA-N 0.000 description 2
- 239000001257 hydrogen Substances 0.000 description 2
- 229910052739 hydrogen Inorganic materials 0.000 description 2
- 150000002990 phenothiazines Chemical class 0.000 description 2
- 238000001228 spectrum Methods 0.000 description 2
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 1
- 239000002246 antineoplastic agent Substances 0.000 description 1
- 229940041181 antineoplastic drug Drugs 0.000 description 1
- 238000005265 energy consumption Methods 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 239000011630 iodine Substances 0.000 description 1
- 238000004519 manufacturing process Methods 0.000 description 1
- 239000000463 material Substances 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- 239000002689 soil Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 229910052717 sulfur Inorganic materials 0.000 description 1
- 239000011593 sulfur Substances 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 238000010189 synthetic method Methods 0.000 description 1
Landscapes
- Nitrogen- Or Sulfur-Containing Heterocyclic Ring Compounds With Rings Of Six Or More Members (AREA)
Abstract
The invention belongs to the technical field of compound synthesis, and particularly discloses a preparation method of phenothiazine. Adding bis (2-bromophenyl) amine, potassium thioacetate and potassium carbonate into an organic solvent, and then adding cuprous iodide to prepare a mixed solution; and heating the mixed solution to react to obtain the phenothiazine. The preparation method of the phenothiazine provided by the invention is simple to operate, simple and convenient in post-treatment, low in raw material cost and easy for industrial production.
Description
Technical Field
The invention relates to the technical field of compound synthesis, in particular to a preparation method of phenothiazine.
Background
Phenothiazine and derivatives thereof are important organic compounds, and have very wide application prospects. For example, the phenothiazine compound can be used as a luminescent material and a dye, and can also be used for preparing antitumor drugs and the like.
At present, a plurality of reports about a preparation method of phenothiazine compounds are mainly synthesized by diphenylamine, derivatives thereof and sulfur under the action of catalysts, and the existing catalysts mainly comprise iodine simple substance, aluminum trichloride and active soil. The currently reported synthetic method of the phenothiazine compounds has the problems of high energy consumption and high production cost.
In order to improve the applicability of phenothiazine compound synthesis and enable the phenothiazine compound to be easier for industrial production, people always search for a more efficient and convenient synthesis method. The invention aims to provide a novel preparation method of phenothiazine.
Disclosure of Invention
The invention mainly solves the technical problem of providing a preparation method of phenothiazine, and has the advantages of simple operation and easy industrial production.
In order to solve the technical problems, the invention adopts the following technical scheme:
a method of preparing phenothiazine, the method comprising the steps of:
(1) Adding bis (2-bromophenyl) amine, potassium thioacetate and potassium carbonate into an organic solvent, and then adding cuprous iodide (CuI) to prepare a mixed solution;
(2) And heating the mixed solution to react to obtain the phenothiazine.
The reaction formula of the phenothiazine preparation method provided by the invention is as follows:
as one embodiment of the present invention, both step (1) and step (2) are carried out under the protection of an inert gas, preferably nitrogen.
As one embodiment of the present invention, in the step (1), the molar ratio of potassium thioacetate to bis (2-bromophenyl) amine is 1.0 to 1.2, preferably 1.1 to 1.2.
As one embodiment of the invention, in the step (1), the feeding mole ratio of the potassium carbonate to the bis (2-bromophenyl) amine is (2.0-3.0): 1.
As one embodiment of the invention, in the 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 of the cuprous iodide to the bis (2-bromophenyl) amine is (0.08-0.12): 1.
In step (1), as an embodiment of the present invention, the organic solvent is DMF (N, N-dimethylformamide), preferably anhydrous DMF.
As an embodiment of the present invention, in the step (2), the reaction temperature of the reaction is 100 to 150℃and preferably 120 to 140 ℃.
As one embodiment of the present invention, in the step (2), the reaction time of the reaction is 10 to 15 hours.
As one embodiment of the present invention, the preparation method of phenothiazine provided by the present invention further includes post-treatment of the reaction liquid obtained by the reaction in step (2), the post-treatment method including:
cooling the reaction liquid obtained in the step (2) to-5 ℃, adding water, and crystallizing at-5 ℃; and then filtering, and drying the obtained solid to obtain the phenothiazine product.
Preferably, the post-treatment method comprises: cooling the reaction liquid obtained in the step (2) to 0 ℃, adding water, and crystallizing at 0 ℃; and then filtering, and drying the obtained solid to obtain the phenothiazine product.
Preferably, in the post-treatment, the volume of water to be added is 3 times or more, preferably 3 to 6 times the volume of the reaction solution.
As a preferred embodiment of the present invention, in step (1), the molar ratio of potassium thioacetate to the bis (2-bromophenyl) amine is 1.1:1, and the molar ratio of potassium carbonate to the bis (2-bromophenyl) amine is 2.5:1; the molar ratio of the cuprous iodide to the bis (2-bromophenyl) amine was 0.10:1.
The invention also provides a phenothiazine product prepared by the method.
The phenothiazine preparation method provided by the invention has the advantages of simple reaction operation, simple post-treatment, cheap and easily obtained raw materials, and easiness in industrial production.
Drawings
FIG. 1 is a nuclear magnetic resonance hydrogen spectrum of a phenothiazine product obtained in example 1 of the present invention.
Detailed Description
The following describes the technical scheme of the present invention in detail by examples.
The raw materials used in the following examples, not specifically described, were all obtained by purchase.
Example 1
The embodiment provides a preparation method of phenothiazine, which comprises the following preparation steps:
bis (2-bromophenyl) amine (32.7 g,0.1 mol), potassium thioacetate (12.5 g,0.11 mol), potassium carbonate (34.5 g,0.25 mol) were added to 400mL anhydrous DMF under nitrogen, followed by cuprous iodide (1.9 g,0.01 mol); after which the mixture was stirred and heated to 130℃and reacted for 12 hours. The reaction was checked by TLC and was complete.
The reaction solution was cooled to 0℃and then 2000mL of water was added thereto, followed by crystallization at 0℃for 10 hours. The mixture was filtered, and the cake was collected and dried to give 18.0g of phenothiazine with a purity of 96%. The nuclear magnetic resonance hydrogen spectrum of the target compound phenothiazine is shown in figure 1.
Example 2
The embodiment provides a preparation method of phenothiazine, which comprises the following preparation steps:
bis (2-bromophenyl) amine (32.7 g,0.1 mol), potassium thioacetate (12.5 g,0.11 mol), potassium carbonate (34.5 g,0.25 mol) were added to 400mL anhydrous DMF under nitrogen, followed by cuprous iodide (1.9 g,0.01 mol); after which the mixture was stirred and heated to 120℃and reacted for 14 hours. The reaction was checked by TLC and was complete.
The reaction solution was cooled to 0℃and then 2000mL of water was added thereto, followed by crystallization at 0℃for 10 hours. The mixture was filtered, and the cake was collected and dried to give 17.8g of phenothiazine with a purity of 97%.
Example 3
The embodiment provides a preparation method of phenothiazine, which comprises the following preparation steps:
bis (2-bromophenyl) amine (32.7 g,0.1 mol), potassium thioacetate (12.5 g,0.11 mol), potassium carbonate (34.5 g,0.25 mol) were added to 400mL anhydrous DMF under nitrogen, followed by cuprous iodide (1.9 g,0.01 mol); after which the mixture was stirred and heated to 150℃and reacted for 10 hours. The reaction was checked by TLC and was complete.
The reaction solution was cooled to 0℃and then 2000mL of water was added thereto, followed by crystallization at 0℃for 10 hours. The mixture was filtered, and the cake was collected and dried to give 17.1g of phenothiazine with a purity of 95%.
Example 4
The embodiment provides a preparation method of phenothiazine, which comprises the following preparation steps:
bis (2-bromophenyl) amine (32.7 g,0.1 mol), potassium thioacetate (11.4 g,0.1 mol), potassium carbonate (34.5 g,0.25 mol) were added to 400mL anhydrous DMF under nitrogen, followed by cuprous iodide (1.9 g,0.01 mol); after which the mixture was stirred and heated to 130℃and reacted for 12 hours. The reaction was checked by TLC and was complete.
The reaction solution was cooled to 0℃and then 2000mL of water was added thereto, followed by crystallization at 0℃for 10 hours. The mixture was filtered, and the cake was collected and dried to give phenothiazine 15.3g with a purity of 96%.
Example 5
The embodiment provides a preparation method of phenothiazine, which comprises the following preparation steps:
bis (2-bromophenyl) amine (32.7 g,0.1 mol), potassium thioacetate (13.7 g,0.12 mol), potassium carbonate (34.5 g,0.25 mol) were added to 400mL anhydrous DMF under nitrogen, followed by cuprous iodide (1.9 g,0.01 mol); after which the mixture was stirred and heated to 130℃and reacted for 12 hours. The reaction was checked by TLC and was complete.
The reaction solution was cooled to 0℃and then 2000mL of water was added thereto, followed by crystallization at 0℃for 10 hours. The mixture was filtered, and the cake was collected and dried to give 17.9g of phenothiazine with a purity of 96%.
Example 6
The embodiment provides a preparation method of phenothiazine, which comprises the following preparation steps:
bis (2-bromophenyl) amine (32.7 g,0.1 mol), potassium thioacetate (12.5 g,0.11 mol), potassium carbonate (34.5 g,0.25 mol) were added to 400mL anhydrous DMF under nitrogen, followed by cuprous iodide (1.9 g,0.01 mol); after which the mixture was stirred and heated to 130℃and reacted for 12 hours. The reaction was checked by TLC and was complete.
The reaction solution was cooled to 0℃and then 800mL of water was added thereto, followed by crystallization at 0℃for 10 hours. The mixture was filtered, and the cake was collected and dried to give 16.2g of phenothiazine with a purity of 85%.
Example 7
The embodiment provides a preparation method of phenothiazine, which comprises the following preparation steps:
bis (2-bromophenyl) amine (227 g,1.0 mol), potassium thioacetate (125.4 g,1.1 mol), potassium carbonate (345 g,2.5 mol) were added to 3L anhydrous DMF under nitrogen, followed by cuprous iodide (19 g,0.1 mol); after which the mixture was stirred and heated to 130℃and reacted for 15 hours. The reaction was checked by TLC and was complete.
The reaction solution obtained is cooled to 0 ℃, then 12L of water is added, and the temperature is kept at 0 ℃ for crystallization for 10 hours. The mixture was filtered, and the cake was collected and dried to give 181g of phenothiazine with a purity of 95%.
The foregoing description is only illustrative of the present invention and is not intended to limit the scope of the invention, and all equivalent modifications made by the teachings of the present invention, or direct or indirect application in other related arts, are included in the scope of the present invention.
Claims (10)
1. A method for preparing phenothiazine, the method comprising the steps of:
(1) Adding bis (2-bromophenyl) amine, potassium thioacetate and potassium carbonate into an organic solvent, and then adding cuprous iodide to prepare a mixed solution;
(2) And heating the mixed solution to react to obtain the phenothiazine.
2. The method according to claim 1, wherein both step (1) and step (2) are carried out under an inert gas atmosphere, preferably nitrogen.
3. The process according to claim 1 or 2, characterized in that in step (1) the molar ratio of potassium thioacetate to bis (2-bromophenyl) amine is (1.0-1.2): 1, preferably the molar ratio is (1.1-1.2): 1.
4. A process according to claim 3, wherein in step (1) the molar ratio of potassium carbonate to bis (2-bromophenyl) amine is from (2.0 to 3.0): 1.
5. The process according to claim 4, wherein 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.
6. The process according to claim 5, wherein in step (1) the organic solvent is DMF, preferably anhydrous DMF.
7. The process according to any one of claims 1 to 6, wherein in step (2) the reaction temperature of the reaction is 100 to 150 ℃, preferably the reaction temperature is 120 to 140 ℃; and/or the reaction time is 10-15 hours.
8. The method according to any one of claims 1 to 7, further comprising a post-treatment of the reaction liquid obtained by the reaction of step (2), the post-treatment method comprising:
cooling the reaction liquid obtained in the step (2) to-5 ℃, adding water, and crystallizing at-5 ℃; and then filtering, and drying the obtained solid to obtain the phenothiazine product.
9. The method according to any one of claims 1-8, wherein in step (1), the molar ratio of potassium thioacetate to the bis (2-bromophenyl) amine is 1.1:1 and/or the molar ratio of 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.
10. A phenothiazine prepared by the method of any one of claims 1-9.
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311808293.1A CN117777052A (en) | 2023-12-26 | 2023-12-26 | Preparation method of phenothiazine |
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| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CN202311808293.1A CN117777052A (en) | 2023-12-26 | 2023-12-26 | Preparation method of phenothiazine |
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| CN117777052A true CN117777052A (en) | 2024-03-29 |
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| CN202311808293.1A Pending CN117777052A (en) | 2023-12-26 | 2023-12-26 | Preparation method of phenothiazine |
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Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118904263A (en) * | 2024-09-23 | 2024-11-08 | 湖北普瑞提化工科技有限公司 | Preparation device and preparation method of phenothiazine |
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2023
- 2023-12-26 CN CN202311808293.1A patent/CN117777052A/en active Pending
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN118904263A (en) * | 2024-09-23 | 2024-11-08 | 湖北普瑞提化工科技有限公司 | Preparation device and preparation method of phenothiazine |
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