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Method for catalytically preparing benzodiazepine compound by using titanocene dichloride

A titanocene dichloride catalysis, benzodiazepine technology, applied in chemical instruments and methods, chemical/physical processes, physical/chemical process catalysts, etc., to achieve the effects of simple operation, non-toxic solvent, and low dosage

Active Publication Date: 2019-09-20
SHAANXI NORMAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0004] The technical problem to be solved by the present invention is to overcome the shortcomings of the existing preparation methods of benzodiazepines, and provide a method for preparing benzodiazepines with simple operation, mild reaction conditions, wide substrate applicability and high efficiency

Method used

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  • Method for catalytically preparing benzodiazepine compound by using titanocene dichloride
  • Method for catalytically preparing benzodiazepine compound by using titanocene dichloride
  • Method for catalytically preparing benzodiazepine compound by using titanocene dichloride

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Preparation of 2,4-diphenyl-3-H-1,5-benzodiazepine with the following structural formula

[0017]

[0018] Add 0.0025g (0.01mmol) titanocene dichloride, 0.0033g (0.02mmol) isophthalic acid, 0.065g (0.6mmol) o-phenylenediamine, 0.103g (0.5mmol) 1,4-diamine to the reaction flask Phenyl-3-butyn-2-one, 1mL ethanol, stirring reaction at room temperature for 5 hours, stop the reaction, remove ethanol by rotary evaporation, separate with silica gel column (elution machine is petroleum ether and ethyl acetate volume ratio is 10: 1) to obtain 2,4-diphenyl-3-H-1,5-benzodiazepine, the yield is 96%, and the spectral data of the product is: 1 H NMR (600MHz, CDCl 3 )δ7.95-7.81(m,4H),7.53(dd,J=6.1,3.5Hz,2H),7.387.31(m,6H),7.27(dd,J=6.1,3.5Hz,2H),7.18 (s,0H),1.53(s,1H); 13 C NMR (101MHz, CDCl 3 )δ154.26, 140.83, 137.34, 130.69, 128.83, 128.77, 128.22, 125.54, 35.01.

Embodiment 2

[0024] Preparation of 2-(4-fluorophenyl)-4-phenyl-3-H-1,5-benzodiazepine with the following structural formula

[0025]

[0026] In this example, the 1,4-diphenyl-3-butane used in Example 1 was replaced with equimolar 1-(4-fluorophenyl)-4-phenyl-3-butyn-2-one Alkyn-2-one, other steps are the same as in Example 1, to obtain 2-(4-fluorophenyl)-4-phenyl-3-H-1,5-benzodiazepine, the yield is 98%, The spectral data of the product are: 1 H NMR (400MHz, CDCl 3 )δ7.97(ddd, J=7.7,4.9,2.0Hz,4H),7.62(dtd,J=7.5,3.5,1.8Hz,2H),7.43(dd,J=5.2,2.0Hz,3H),7.35 (dd,J=6.2,3.5Hz,2H),7.09(t,J=8.6Hz,2H); 13 C NMR (101MHz, CDCl 3 )δ 165.55, 163.05, 153.95, 152.78, 140.72, 140.59, 137.22, 133.58, 133.55, 130.74, 130.37, 130.28, 128.79, 128.72, 128.18, 128.14, 125.594, 115.8

Embodiment 3

[0028] Preparation of 2-(4-chlorophenyl)-4-phenyl-3-H-1,5-benzodiazepine with the following structural formula

[0029]

[0030] In this example, the 1,4-diphenyl-3-butane used in Example 1 was replaced with equimolar 1-(4-chlorophenyl)-4-phenyl-3-butyn-2-one Alkyn-2-one, other steps are the same as in Example 1, to obtain 2-(4-chlorophenyl)-4-phenyl-3-H-1,5-benzodiazepine, the yield is 98%, The spectral data of the product are: 1 H NMR (400MHz, CDCl 3 )δ7.96(dd, J=7.5,2.3Hz,2H),7.91(d,J=8.6Hz,2H),7.65-7.57(m,2H),7.46-7.41(m,3H),7.39(s ,1H),7.38-7.32(m,3H); 13 C NMR (101MHz, CDCl 3 )δ153.90, 152.68, 140.76, 140.47, 137.15, 136.91, 135.70, 130.78, 129.45, 128.95, 128.80, 128.73, 128.16, 125.69, 125.58, 34.82.

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Abstract

The invention discloses a method for catalytically preparing a benzodiazepine compound by using titanocene dichloride. According to the method, a 3-butyne-2-ketone compound and an o-phenylenediamine compound are taken as raw materials, ethanol or methanol is taken as a solvent and an accelerant, titanocene dichloride is taken as a catalyst, and isophthalic acid and 2-hydroxy nicotinic acid or salicylic acid is taken as a ligand to high efficiently prepare the 2,4-diphenyl-3-H-1,5-benzodiazepine derivative in a high-yield mode. The usage amount of the catalyst used in the method is low, and the catalyst is low in price, is free of toxicity and is stable in air; the reaction is mild in conditions, short in time and simple in operation; and after the reaction is finished, only simple column chromatography separation is needed to be carried out on the product to obtain the 2,4-diphenyl-3-H-1,5-benzodiazepine derivative. A novel low-cost green and efficient way is developed for preparation of the 2,4-diphenyl-3-H-1,5-benzodiazepine derivative, and the method has a wide application prospect.

Description

technical field [0001] The invention belongs to the technical field of synthesis of benzodiazepine compounds, and in particular relates to a kind of isophthalic acid, 2-hydroxynicotinic acid or salicylic acid used as a ligand to promote titanocene dichloride to catalyze 3-butyne-2-one A method for efficiently preparing benzodiazepines by reacting benzodiazepines with o-phenylenediamines. Background technique [0002] Benzodiazepines are a class of widely existing alkaloid compounds, which are used in various fields due to their biological activity and high pharmacological activity, including alcohol withdrawal symptoms, insomnia, anxiety, anti-inflammatory, anti- Convulsions, sedatives and painkillers, some of which are used to treat cancer, cardiovascular disease and AIDS. [0003] At present, there are roughly three synthesis methods for benzodiazepines, namely, the reaction of 1,3-diketone compounds with o-phenylenediamine, the reaction of nitrile groups or other unsatur...

Claims

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Application Information

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IPC IPC(8): C07D243/12B01J31/22
CPCC07D243/12B01J31/2295B01J2531/842B01J2531/0225
Inventor 高子伟杨明明苏洁庄梦媛孙华明
Owner SHAANXI NORMAL UNIV
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