Method for preparing bis (indolyl) methane derivative in presence of amine salt

Abstract

The invention discloses a method for preparing a bis (indolyl) methane derivative in the presence of an amine salt. According to the method, by taking the amine salt as a catalyst, indole or an indole derivative is reacted with aldehyde to obtain the bis (indolyl) methane derivative, wherein the amine salt is aniline hydrochloride, o-chloroaniline hydrochloride, o-methoxyaniline hydrochloride, pyrrole hydrochloride, aniline trifluoromethane sulphonate or aniline trifluoroacetate. The method disclosed by the invention is simple in operation, mild in reaction condition, short in reaction time, good in substrate applicability and high in target matter yield; the catalyst is cheap and easily available, free of toxicity and stable to air and water; therefore, the method can be widely used for the preparation of the bis (indolyl) methane derivative.

Description

technical field [0001] The present invention relates to a process for the preparation of bisindolylmethane derivatives in the presence of amine salts. Background technique [0002] Bis-indole alkyl compounds and their derivatives are a class of metabolites widely found in flower plants, continental and marine protozoa, and most of them have certain physiological activities, such as: anti-tumor, anti-virus, anti-bacterial and anti-inflammatory, etc. . Bisindole alkyl compounds are also key intermediates in the synthesis of many alkaloids with complex structures, which can be used to construct dendrimer frameworks. In addition, bis-indole alkyl compounds are also commonly used in dyes. 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 compound mainly uses Bronsted acid or Lewis acid as a c...

AI Technical Summary

Problems solved by technology

2003 B.P.Bandgar (Tetrahedron Letters 44 (2003) 1959-1961) with I 2 As a catalyst, bis-indolylmethane derivatives are prepared at room temperature, but the amount of catalyst used in this method is too much

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 the catalyst preparation steps are cumbersome and require TiCl, which is extremely sensitive to air. 4 , multiple treatments at 100°C for up to 36 hours, and then secondary treatment at a high temperature of 600°C, the harsh preparation conditions greatly limit its application

Later, Claudio C. Silveira used glycerol and CeCl 3 (Tetrahedron Letters50 (2009) 6060-6063) as catalyst synthesis bis-indolylmethane derivative, this catalyst can be recycled, but used noble metal in the catalyst, the price is expensive, and the required temperature of reaction is higher

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 2011, Tomasz M. Kubczyk used nanoporous aluminosilicate (Green Chem., 2011, 13, 2320-2325) to catalyze indoles and aldehydes to obtain bis-indolylmethane derivatives. This catalyst is stable to water and heat, but the preparation of catalysts The process is complicated

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

2013 [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.

TPPMS / CBr appeared in the same year 4 (ACS Sustainable Chem.Eng.2013, 1, 549-553) as a catalyst to catalyze indole and carbonyl compounds and acetals to obtain bis-indole alkyl compounds. The catalyst is stable and easy to obtain, does not require anhydrous and oxygen-free conditions, and can be recycled Catalyzed 10 times, but the substrate requirements are high and the catalytic system is complex

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 long reaction time, expensive metal catalysts, high substrate activity requirements, harsh reaction conditions, and unsafe operating procedures.

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