Method for preparing diindolyl methane derivatives

Abstract

The invention discloses a method for preparing diindolyl methane derivatives. The method comprises the following step: with titanocene dichloride and a ligand as catalysts, reacting indole and aldehyde to obtain the diindolyl methane derivative under an alkaline condition, wherein the ligand can be 8-hydroxyquinoline, catechol and o-aminophenol and the alkali is aniline, pyridine, pyrrole or triethylamine. The method is easy to operate, the reaction is high-efficiency and mild, the catalysts are low in price, non-toxic, stable to air and water, and substrate applicability is good; therefore, the method can be widely applied to preparation of diindolyl methane derivatives.

Description

technical field [0001] The invention relates to a preparation method of bis-indolylmethane derivatives. Background technique [0002] Bisindole alkyl compounds and their derivatives are a class of metabolites that widely exist in mainland and marine protozoa, and most of them have certain physiological activities, such as: anti-tumor, anti-virus, anti-bacterial and anti-inflammatory, etc. Inolealkyl compounds are also key intermediates in the synthesis of many alkaloids with complex structures. With the continuous expansion of the application fields of bis-indolylmethane and its derivatives, its preparation has attracted widespread attention from organic chemists and pharmacologists. [0003] The preparation of bis-indole alkyl compounds is mainly carried out by indole and aldehyde or ketone under the action of Bronsted acid or Lewis acid catalyst. In 2002, Chakrabarty (Tetrahedron, 2002, 43: 4075-4078) used montmorillonite K-10 as a catalyst to prepare bis-indolylmethane ...

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Problems solved by technology

In 2005, Ji Shunjun of Soochow University and others (CN1706829A) used solid acid SO 4 2- / TiO 2 As a catalyst, indole and aldehyde are prepared in one step to obtain bis-indolylmethane derivatives. This method is efficient and simple, but requires a large amount of catalyst, and the preparation of the catalyst uses TiCl, which is extremely sensitive to air. 4 , needs to be treated at 100°C for up to 36 hours, and then processed at a high temperature of 600°C. The preparation steps of the catalyst are cumbersome and the harsh conditions greatly limit its application.

Later, S-R Sheng (catal. Lett., 2009, 128, 418-422) used PEG-supported sulfonic acid catalyst to react in ethanol solvent at room temperature for 2 to 9 hours to prepare bis-indolylmethane derivatives. Although the catalyst can be recovered by this method, the recovery The process needs to use a large amount of ether, and the operation process is complicated

2010InCl 3 (Carbohydr.Res.2010,345,1708), FeCl 3 (J.Org.Chem.2010, 75(15):5240-5249) and other simple Lewis acid catalysts are used to catalyze indoles and imines to efficiently prepare bis-indolylmethane derivatives, but the raw materials required for the reaction It is an N-substituted sulfonimide with higher activity, and its preparation steps are complicated and the imine has certain toxicity

In 2012, Li Bailin (CN102766081A) of Taizhou University disclosed a method using ionic liquid [(HSO 3 -p) 2 im][CF 3 SO 3 ] is a method for preparing bis-indolylmethane derivatives as a catalyst, the method is highly efficient and mild, but the preparation of dialkylsulfonic acid ionic liquids is complicated and expensive

Recently, [Ir(COD)(SnCl 3 )Cl(m-Cl)] 2 The complex (Tetrahedron, 2013, 69: 2816-2826) was found to be able to catalyze the reaction of N-sulfonimide and indole to prepare bis-indolylmethane derivatives. However, it is expensive and the raw materials are also not easy to obtain

In addition, xanthic acid, LiClO 4 , In(OTf) 3 , Y(OTf) 3 、Dy(OTf) 3 etc. are also used to catalyze the preparation of such compounds. These methods have certain shortcomings, such as too long reaction time, the use of expensive metal catalysts, harsh reaction conditions, and insufficient safety in the operation process.

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