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Method for synthesizing 1,2,4-benzothiadiazine series compounds in aqueous solution

A technology of benzothiadiazines and compounds, which is applied in the field of preparation of 1,2,4-benzothiadiazines compounds, can solve the problems of increased production costs and high equipment requirements, and achieves extremely easy acquisition and high product yield High, high chemoselectivity effect

Active Publication Date: 2022-05-24
JIANGXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, a potential problem in this method is that the cobalt catalyst will decompose and release a small amount of toxic gas carbon monoxide during the reaction, and the reaction also needs to use silver salt as a co-catalyst. In addition, the compound 3-aryl (alkyl) base-1,4, 2-Oxadiazol-5-one needs to be additionally prepared as a reaction raw material, and halogenated hydrocarbon trichloromethane is used as an organic solvent in the reaction. These factors will lead to high requirements for equipment and increased production during large-scale preparation. Potential issues with cost

Method used

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  • Method for synthesizing 1,2,4-benzothiadiazine series compounds in aqueous solution
  • Method for synthesizing 1,2,4-benzothiadiazine series compounds in aqueous solution
  • Method for synthesizing 1,2,4-benzothiadiazine series compounds in aqueous solution

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Experimental program
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Effect test

Embodiment 1

[0031]

[0032] The catalyst cuprous oxide (2.1mg, 0.015mmol) and 2-bromophenylmethyliminosulfone (70.4mg, 0.3mmol) and tetrabutylammonium iodide (11.0mg, 0.03mmol) and benzaldehyde were mixed under air atmosphere (41.4 mg, 0.39 mmol) was dissolved in water (1 mL), then sodium azide (39.0 mg, 0.6 mmol) was added to seal and then placed in a 90°C environment to react for 12 hours. After the reaction was completed by TLC, it was cooled to room temperature, and water was added. (2mL), then add saturated potassium carbonate solution (2mL) and stir for 10 minutes, extract 4 times with ethyl acetate, combine the organic phases and dry with anhydrous sodium sulfate, the pure product 3a separated by flash column chromatography, the yield is 95% . The following is the NMR experimental data of product 3a:

[0033] 1 H NMR (400MHz, CDCl 3 )δ: 8.38(d,J=7.2Hz,2H),7.80(d,J=8.0Hz,1H),7.69(t,J=7.6Hz,1H),7.62(d,J=8.0Hz,1H) ,7.45(d,J=6.4Hz,3H),7.38(t,J=7.4Hz,1H),3.52(s,3H).

[0034] 13...

Embodiment 2

[0036]

[0037] The catalyst cuprous oxide (2.1g, 15mmol) and 2-bromophenylmethyliminosulfone (70.4g, 0.3mol) and tetrabutylammonium iodide (11.0g, 0.03mol) and benzaldehyde ( 41.4g, 0.39mol) was dissolved in water (1L), then sodium azide (39.0g, 0.6mol) was added to seal and then placed in a 90°C environment to react for 12 hours. After TLC detected the reaction, it was cooled to room temperature, and water ( 2L), then add saturated potassium carbonate solution (2L), stir for 10 minutes, extract 4 times with ethyl acetate, combine the organic phases and dry with anhydrous sodium sulfate, and separate the pure product 3a by flash column chromatography, the yield is 90%.

Embodiment 3

[0039]

[0040] The catalyst cuprous oxide (2.1g, 15mmol) and 2-bromophenylmethyliminosulfone (70.4g, 0.3mol) and tetrabutylammonium bromide (7.9g, 0.03mol) and benzaldehyde ( 41.4g, 0.39mol) was dissolved in water (1L), and then methanesulfonyl azide (72.6g, 0.6mol) was added to seal it and then placed in a 90°C environment to react for 12 hours. After the reaction was detected by TLC, it was cooled to room temperature and water was added. (2L), then add saturated potassium carbonate solution (2L) and stir with ethyl acetate for 4 times after stirring for 10 minutes, combine the organic phases and dry with anhydrous sodium sulfate, the pure product 3a separated by flash column chromatography, the yield is 90% .

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Abstract

The invention provides a preparation method of 1,2,4-benzothiadiazine-1-oxide series compounds. The method adopts a one-pot reaction, utilizes 2-bromophenyliminosulfone and aryl (alkyl) aldehydes that can be directly purchased commercially as reaction substrates, stable, cheap and non-toxic copper oxides as catalysts, and water as green Using a non-polluting solvent, react at 80-100°C for 12-15 hours in an air environment to synthesize 1,2,4-benzothiadiazine series compounds. The present invention uses water as a solvent, basically has no pollution to the environment, does not require alkali and inert gas protection, has no special requirements for reaction equipment, is easy to operate, adopts a one-pot reaction, and saves the operation of preparing and separating intermediates, so the synthesis cost extremely low. The product obtained in the present invention has excellent chemoselectivity, high production efficiency, wide compatibility of substrate functional groups, conforms to green reaction characteristics, is suitable for large-scale preparation, has excellent industrial application prospects, and is an environmentally friendly green product. chemical technology.

Description

technical field [0001] The invention relates to a derivative of a sulfur-containing and diazide heterocyclic drug skeleton, in particular to a preparation method of a 1,2,4-benzothiadiazine compound. Background technique [0002] Imidosulfone derivatives have important physiological and pharmacological activities. At present, the marketed drugs containing iminosulfone skeleton structure, that is, the structure containing sulfur-oxygen and sulfur-nitrogen double bonds, are: Suloxifen (Suloxifen) for the treatment of asthma and asthma, HE-HK 52 for relieving spasm, Sulfoxaflor (Sulfoxaflor) for anthelmintic and insecticide, Sudexanox (Sudexanox) for anti-allergy, pan-CDK (ZK 304709) for inhibiting cyclins (CDKs) activating enzymes, and lymphocyte inhibition NSC 287474 of HIV Reverse Transcriptase et al. [0003] Among the imidosulfone series derivatives, the benzo[e][1,2,4]thiadiazole-1-oxo derivatives with a phenyl ring structure are the most important heterocyclic skeleton...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): C07D285/24C07D417/04
CPCC07D285/24C07D417/04
Inventor 陈知远吴翠
Owner JIANGXI NORMAL UNIV
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