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Method for preparing N-(substituent) benzothiazine-4-ketone without metal participation

A benzothiazine and substituent technology, which is applied in the field of preparing N-benzothiazine-4-one without metal participation, can solve the problems of low yield of target product, pungent smell, high price and the like

Active Publication Date: 2022-03-15
CHANGZHOU UNIV
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  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0003] The first method, using N-substituted-2-methanesulfinyl benzamide as a raw material, obtains the target product under the action of tert-butyldimethyl (1-methoxyethyleneoxy) silane and zinc iodide N-substituted benzothiazin-4-ketones, the weak point of this method: at first use expensive and toxic silicon reagent tert-butyldimethyl (1-methoxyethyleneoxy) silane, secondly the raw material of reaction needs Prepared by the corresponding thioether, the steps are cumbersome and the efficiency is not high
[0004] The second method, using o-carboxythiophenol, formaldehyde and corresponding amines as raw materials, reflux in toluene to obtain the target product N-substituted benzothiazin-4-one, the disadvantage of this method is to obtain the target product low yield At the same time, o-carboxythiophenol and formaldehyde are used as reaction raw materials, which have a pungent smell and are more harmful to the body
The disadvantage of this method is that the metal reagent silver oxide is needed, and the raw material must contain methylthio, and the substrate adaptability is poor.

Method used

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  • Method for preparing N-(substituent) benzothiazine-4-ketone without metal participation
  • Method for preparing N-(substituent) benzothiazine-4-ketone without metal participation
  • Method for preparing N-(substituent) benzothiazine-4-ketone without metal participation

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Example 1: Synthetic method: Acetonitrile (10 mL), N-(n-butyl)-2-thioethylbenzamide (1 mmol, 0.237 g), 1-chloromethyl-4 -Fluoro-1,4-diazabicyclo[2.2.2]octane bis(tetrafluoroborate) salt (1mmol, 0.35g), sodium iodide (3mmol, 0.450g) and hydroiodic acid (1mmol, 0.065ml ), the anti-temperature was controlled at 120 degrees centigrade, and the reaction was vigorously stirred for 24 hours. After the reaction was completed, the reaction solution was concentrated and separated by column chromatography in sequence to obtain N-(n-butyl)benzothiazin-4-one (0.176 g, 80%).

[0017] The equations involved in the reaction are as follows:

[0018]

[0019] The NMR data and mass spectrum data of the target product N-(n-butyl)benzothiazin-4-one 1 are as follows:

[0020] 1 H NMR (300MHz, CDCl 3 )δ8.05–8.02(m,1H),7.30–7.25(m,1H),7.21–7.16(m,2H),4.49(s,2H),3.56(t,J=7.2Hz,2H),1.63 –1.53(m,2H),1.40–1.30(m,2H),0.89(t,J=7.3Hz,3H).

[0021] 13 C NMR (75MHz, CDCl 3 )δ163.70, 137.02, ...

Embodiment 2

[0023] Embodiment 2: according to the method of specific embodiment 1, carried out N substituent substrate extension, wherein N substituting group can be: methyl group, benzyl group and cyclohexyl group, concrete data are as follows:

[0024]

[0025] (1) N-(methyl)benzothiazin-4-one 2: 1 H NMR (300MHz, CDCl 3 )δ8.06–8.03(m,1H),7.32–7.26(m,1H),7.22–7.17(m,2H),4.51(s,2H),3.17(s,3H). 13 C NMR (75MHz, CDCl 3 )δ163.14,135.81,130.54,129.58,128.23,126.07,125.14,49.07,34.71.MS(ESI,m / z):180.0[M+H] + .

[0026] (2) N-(Benyl)benzothiazin-4-one 2: 1 H NMR (300MHz, CDCl 3 )δ8.14–8.10(m,1H),7.33–7.18(m,8H),4.80(s,2H),4.43(s,2H). 13 C NMR (75MHz, CDCl 3 )δ164.05,137.08,136.36,131.74,130.95,129.28,128.84,128.08,127.83,127.19,126.19,51.08,47.76.MS(ESI,m / z):256.1[M+H] + .

[0027] (3) N-(cyclohexyl)benzothiazin-4-one 3: 1 H NMR (300MHz, CDCl 3 )δ8.06–8.03(m,1H),7.30–7.24(m,1H),7.21–7.16(m,2H),4.62–4.51(m,1H),4.44(s,2H),1.80–1.75( m,4H),1.66–1.61(m,1H),1.42–1.31(m,4H),1.12–1.00(m...

Embodiment 3

[0028] Embodiment 3: According to the method of specific embodiment 1, carried out S substituent (R) substrate expansion, wherein S substituent (R) can be methyl, propyl, butyl, and benzyl, specific data are as follows:

[0029]

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Abstract

The invention belongs to the field of fine chemical engineering, and relates to a method for preparing N-(substituent) benzothiazine-4-ketone without metal participation. Comprising the following steps: sequentially adding N-(substituted)-2-sulfur alkyl benzamide, 1-chloromethyl-4-fluoro-1, 4-diazabicyclo [2.2. 2] octane bis (tetrafluoroborate) salt, sodium iodide and hydroiodic acid into a sealed tube containing a reaction solvent acetonitrile, heating, violently stirring and reacting to obtain the N-(substituted) benzothiazine-4-ketone. The sulfanyl group in the reaction substrate is subjected to C-S bond breakage firstly, then the chloromethyl group in the additive is transferred into the substrate, construction of C-S and C-N is achieved at the same time, and construction of the benzothiazine-4-ketone is achieved. The method has the characteristics of greenness and high efficiency.

Description

technical field [0001] The invention belongs to the field of fine chemicals, and relates to a method for preparing N-(substituent)benzothiazin-4-one without metal participation. Background technique [0002] The N-substituted benzothiazin-4-one derivatives have antitumor activity, antimalarial activity and medicinal activities such as myocardial protection. Currently, there are three main synthetic methods of N-substituted benzothiazin-4-one compounds reported in the literature: [0003] The first method, using N-substituted-2-methanesulfinyl benzamide as a raw material, obtains the target product under the action of tert-butyldimethyl (1-methoxyethyleneoxy) silane and zinc iodide N-substituted benzothiazin-4-ketones, the weak point of this method: at first use expensive and toxic silicon reagent tert-butyldimethyl (1-methoxyethyleneoxy) silane, secondly the raw material of reaction needs Prepared by the corresponding thioether, the steps are cumbersome and the efficiency ...

Claims

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Application Information

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IPC IPC(8): C07D279/08
CPCC07D279/08
Inventor 杨科戴胜飞李正义孙小强
Owner CHANGZHOU UNIV
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