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Preparation method for 2-(alpha-hydroxyl aryl) benzimidazole compound

A benzimidazole and hydroxyaryl technology, applied in the field of organic compound synthesis, can solve the problems of high reaction temperature, poor substrate universality, and low yield, and achieve good substrate universality, mild reaction conditions, and high yield. high rate effect

Active Publication Date: 2019-06-28
HENAN NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0003] However, these existing synthetic methods have shortcomings such as low yield, high reaction temperature, pre-synthesis of chiral 2-hydroxy-2-phenylacetic acid, poor substrate universality, etc., which undoubtedly limit its application range

Method used

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  • Preparation method for 2-(alpha-hydroxyl aryl) benzimidazole compound
  • Preparation method for 2-(alpha-hydroxyl aryl) benzimidazole compound
  • Preparation method for 2-(alpha-hydroxyl aryl) benzimidazole compound

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0024] Example 1 Preparation of 1-tert-butoxycarbonyl-2-(α-hydroxyphenyl)benzimidazole, the structural formula is as follows:

[0025] .

[0026] Preparation: In a dry 25 mL schlenk tube, add 1-tert-butoxycarbonyl-2-benzoyl-benzimidazole (0.097 g, 0.3 mmol), photosensitizer (0.00053 g, 0.0015 mmol), N-phenylpiperene Pyridine (0.097 g, 0.6 mmol) and chiral spirocyclic phosphoric acid catalyst (0.028 g, 0.03 mmol), continue to add 5 mL of cyclopentyl methyl ether, and degas with a vacuum pump for 3 times at -78 ° C, 5 min each time , and then placed at -30°C and irradiated with a 3W blue light for 48 hours. After complete reaction, separate by column chromatography (petroleum ether / ethyl acetate = 20 / 1 ~ 8 / 1), concentrate by rotary evaporation, and dry in vacuum (at 25°C for 1 hour) to obtain 1-tert-butoxycarbonyl- 2-(α-Hydroxyphenyl)benzimidazole (0.079 g, 0.243 mmol), yield 81%. The detection results of its hydrogen spectrum and carbon spectrum are as follows (see figur...

Embodiment 2

[0034] Example 2 Preparation of 1-tert-butoxycarbonyl-2-(α-hydroxy-4-methylphenyl)benzimidazole, the structural formula is as follows:

[0035] .

[0036] Preparation process: Add 1-tert-butoxycarbonyl-2-(4-methylbenzoyl)-benzimidazole (0.1 g, 0.3 mmol), photosensitizer (0.00053 g, 0.0015 mmol) into a dry 25 mL schlenk tube ), N-phenylpiperidine (0.097g, 0.6 mmol) and chiral spirocyclic phosphoric acid catalyst (0.028 g, 0.03 mmol), continue to add 5 mL of cyclopentyl methyl ether, and degas with a vacuum pump at -78 °C 3 times, 5min each time, then placed at -30°C and irradiated with a 3W blue light for 48 hours. After complete reaction, separate by column chromatography (petroleum ether / ethyl acetate = 20 / 1 ~ 8 / 1), concentrate by rotary evaporation, and dry in vacuum (at 25°C for 1 hour) to obtain 1-tert-butoxycarbonyl -2-(α-Hydroxy-4-methylphenyl)benzimidazole (0.087 g, 0.258 mmol), yield 86%, enantiomeric excess 90%. The spectrum detection results are as follows:

[...

Embodiment 3

[0038] Example 3 Preparation of 1-tert-butoxycarbonyl-2-(α-hydroxy-4-fluorophenyl)benzimidazole, the structural formula is as follows:

[0039] .

[0040] Preparation process: Add 1-tert-butoxycarbonyl-2-(4-fluorobenzoyl)-benzimidazole (0.1 g, 0.3 mmol), photosensitizer (0.00053 g, 0.0015 mmol) into a dry 25 mL schlenk tube, N-phenylpiperidine (0.097 g, 0.6 mmol) and chiral spirocyclic phosphoric acid catalyst (0.028 g, 0.03 mmol), continue to add 5 mL of cyclopentyl methyl ether, and degas with a vacuum pump at -78 °C for 3 time, 5min each time, and then placed at -30°C and irradiated with a 3W blue light for 48 hours. After complete reaction, separate by column chromatography (petroleum ether / ethyl acetate = 20 / 1 ~ 8 / 1), concentrate by rotary evaporation, and dry in vacuum (at 25°C for 1 hour) to obtain 1-tert-butoxycarbonyl -2-(α-Hydroxy-4-fluorophenyl)benzimidazole (0.075 g, 0.228 mmol), yield 76%, enantiomeric excess 90%. The spectrum detection results are as follows...

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Abstract

The invention discloses a preparation method for an optically pure 2-(alpha-hydroxyl aryl) benzimidazole compound. The preparation method comprises the specific steps that 1-butyloxycarboryl-2-arylcyclopropane-benzimidazole is mixed with a photosensitizer, N-phenylpiperidine, a chiral catalyst and an organic solvent, under the condition that the temperature is equal to or lower than -78 DEG C, degassing is conducted 2-3 times by using a vacuum pump, degassing is conducted for 5-10 minutes at a time, and then the mixture is exposed to a 3-10 W blue lamp at the temperature of -28 DEG C--32 DEG C, a reaction is carried out for 20-48 hours, after the reaction is finished, column chromatography separation, rotary evaporation and vacuum drying are conducted in sequence, and then the product is obtained. By means of the method, the optically pure 2-(alpha-hydroxyl aryl) benzimidazole compound can be directly, efficiently and generally synthesized. The method has the advantages of being mild in reaction condition, high in yield and high in substrate universality.

Description

technical field [0001] The invention belongs to the technical field of organic compound synthesis, and in particular relates to a preparation method of a class of optically pure 2-(α-hydroxyaryl)benzimidazole (HBB) compounds. Background technique [0002] Hydroxyl and benzimidazole are important structural units of a variety of physiologically active molecules, so the combination of these two structural units has potential application value in drug development. For example, 2-(alpha-hydroxyaryl) benzimidazoles have the effect of inhibiting viral RNA proliferation (I.Tamm, H.J.Eggers, Science 1963, 142 , 24−33; S.B. Kadin, H. J. Eggers, I. Tamm, Nature 1964, 201 , 639−640; S. Akihama, M. Okude, K. Sato, S. Iwabuchi, Nature 1968, 217 , 562; I. Tamm, H. J. Eggers, R. Nature 1969, 223 , 785; D. G. O'Sullivan, A. K. Wallis, J. Med. Chem. 1972, 15 ,103.); 2-(α-hydroxyaryl)benzimidazoles combined with cisplatin can reduce the toxicity of cisplatin (M. Gökçe, S.Utku, S...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D235/12
Inventor 江智勇乔保坤赵筱薇李春阳
Owner HENAN NORMAL UNIV
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