Novel method for preparing chiral sulphoxide compound

A technology for compounds and titanium compounds, applied in the field of chiral sulfoxide compounds, can solve the problems of no enantioselective oxidation of thioethers, no disclosure of a single enantiomer, etc., and achieve the effects of simple method and high optical purity of products

Inactive Publication Date: 2009-09-23
CHENGDU ORGANIC CHEM CO LTD CHINESE ACAD OF SCI +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

In the prior art, there is no disclosure of chiral (+)- or (-)-metal titanium complexes of tartrate diamides to catalyze the preparation of 2-[[(2-pyridyl)methylene]sulfinyl]-1H- A method for the single enantiomer of benzimidazole compounds, and a method for the enantioselective oxidation of thioethers catalyzed by (+)- or (-)-tartrate monosubstituted amines

Method used

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  • Novel method for preparing chiral sulphoxide compound
  • Novel method for preparing chiral sulphoxide compound
  • Novel method for preparing chiral sulphoxide compound

Examples

Experimental program
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Effect test

Embodiment 1

[0045] Example 1 The effect of the structure of the chiral tartrate diamide bidentate ligand on the enantioselective catalytic oxidation reaction:

[0046] 0.31 g (0.95 mmol) of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]thio]-1H-benzo Imidazole was dissolved in 2.5 ml of toluene with stirring at 70°C. Add 0.264 g (1.14 mmol) tartrate diamide at 60° C., and stir for 15 minutes. 0.16 g (0.57 mmol) of titanium tetraisopropoxide was added under heat preservation, and after heat preservation and stirring for 1 hour, 4.4 mg (0.24 mmol) of water was added, and heat preservation and stirring were carried out for 20 minutes. The temperature was lowered to 0°C, and 0.2 ml (1.05 mmol) of phenylisopropyl hydroperoxide was added dropwise. React at 0°C for 24 hours, add 50 ml of 10% sodium hydroxide solution and shake several times, then wash the aqueous solution twice with toluene, adjust the pH value of the aqueous layer to 7-8 with glacial acetic acid, extract with dichlor...

Embodiment 2

[0050] The influence of embodiment 2 additives on the enantioselective catalytic oxidation reaction:

[0051] 0.31 g (0.95 mmol) of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]thio]-1H-benzimidazole Dissolve in 2.5 ml of toluene with stirring at 70°C. Add 0.132 g (0.57 mmol) of D-di-n-propionamide tartrate at 60° C., and stir for 15 minutes. 0.08 g (0.285 mmol) of titanium tetraisopropoxide was added under heat preservation, and after stirring for 1 hour, 2.2 mg (0.1 mmol) of water was added and stirred at 60° C. for 20 minutes. Cool down to 30°C, add 0.285 mmol of additives, keep stirring for 10 minutes, then cool down to 0°C, add 0.2 ml (1.05 mmol) of phenylisopropyl hydroperoxide dropwise. React at 0°C for 24 hours, add 50 ml of 10% sodium hydroxide solution and shake several times, then wash the aqueous solution twice with toluene, adjust the pH value of the aqueous layer to 7-8 with glacial acetic acid, extract with dichloromethane, The organic phase was was...

Embodiment 3

[0055] The enantioselective catalytic oxidation reaction under the room temperature condition of embodiment 3:

[0056] 0.31 g (0.95 mmol) of 5-methoxy-2-[[(4-methoxy-3,5-dimethyl-2-pyridyl)methyl]thio]-1H-benzimidazole Dissolve in 2.5 ml of toluene with stirring at 70 °C. Add 0.132 g (0.57 mmol) di-n-propionamide tartrate at 60°C, stir for 15 minutes, then add 0.08 g (0.285 mmol) titanium tetraisopropoxide, keep stirring for 1 hour, then add 2.2 mg (0.1 mg) mol) water, stirred at 60°C for 20 minutes. Cool down to 30°C, add 0.285 mmol of additives, stir for 10 minutes, and then add dropwise 0.2 ml (1.05 mmol) of phenylisopropyl hydroperoxide. After reacting at 30°C for 5 hours, add 50 ml of 10% sodium hydroxide solution and shake several times, then wash the aqueous solution twice with toluene, adjust the pH value of the aqueous layer to 7-8 with glacial acetic acid, and extract with dichloromethane , and then washed the organic phase twice with saturated saline, dried over...

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Abstract

The invention provides a novel method for preparing optically pure substituted [(pyridyl methylene) sulfinyl]-1H-benzimidazole sulphoxide compound by enantioselective synthesis. The method requiring protection is to directly and asymmetrically oxidize prochiral thioether into a corresponding optically pure sulphoxide compound or a sulphoxide compound rich in single enantiomer by a mild and cheap oxidizing agent in the presence of a complex compound catalyst formed by an accessible and stable (+)- or (-)- tartaric acid diamide ligand shown in a general formula and titanium. Therefore, optically pure omeprazole, lansoprazole and pantoprazole can be obtained, wherein R8, R9, R10 and R11 are the same or different, and are selected from hydrogen, alkyl, aralkyl, aryl, organic polymers or a silica loading body.

Description

field of invention [0001] The invention relates to a method for preparing enantiomer-enriched or optically pure chiral sulfoxide compounds with anti-peptic ulcer activity by enantioselective catalytic oxidation. technical background [0002] With 2-[[(2-pyridyl)methylene]sulfinyl]-1H-benzimidazole structure or structurally related sulfoxide compounds I can inhibit H + , K + - The activity of ATPase (also known as proton pump), which inhibits gastric acid secretion, has been widely used to treat peptic ulcers caused by hypersecretion of gastric acid, and its related diseases. [0003] [0004] Omeprazole: R 1 =CH 3 , R 2 =OCH 3 , R 3 =CH 3 , R 4 = R 6 = R 7 = H, R 5 =OCH 3 [0005] Lansoprazole: R 1 = H, R 2 =OCH 2 CF 3 , R 3 =CH 3 , R 4 = R 5 = R 6 = R 7 =H [0006] Pantoprazole: R 1 = H, R 2 =OCH 3 , R 3 =OCH 3 , R 4 = R 6 = R 7 = H, R 5 =OCHF 2 [0007] In the asymmetrically substituted sulfoxide compounds, the sulfur atom is chiral, a...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/12C07B53/00
CPCC07D401/12A61P1/04
Inventor 廖建田添黄晴菲邓金根朱槿朱剑平
Owner CHENGDU ORGANIC CHEM CO LTD CHINESE ACAD OF SCI
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