Catalyst Free Synthesis of Bis(Indolyl)Methanes and 3,3‐Bis(Indolyl)oxindoles in Aqueous Ethyl Lactate

Abstract

A highly efficient and environmentally friendly approach has been reported for the synthesis of bis(indolyl)methanes and 3,3‐bis(indolyl)oxindoles by reacting of indoles with aldehydes or isatins in water‐ethyl lactate under ultrasound irradiation. This protocol presents the benefits of catalyst‐free, operational simplicity, short reaction time, high product yield, broad substrate scope and applicability for large‐scale synthesis.

Ethyl lactate: An Efficient Green Mediator for Transition Metal Free Synthesis of Symmetric and Unsymmetric Azobenzenes

“…We then decided to use ethyl lactate (EL) as the solvent and we were excited to find the yield increased to 78% (Table 1, Entry 11). We also used the solution of EL/H 2 O at different ratios but yield remained almost the same (Table 1, Entry 10,11,12). Now with the solvent being optimized, we increased the amount of oxone to 1.0 mmol but here we were surprised to find that yield decreased considerably to 62% (Table 1, Entry 13).…”

“…[3] It also has been fruitfully engaged in the extraction of various bioactive compounds and diverse food such as carotenoids, [4] polyphenols, [5] amino acids [6] and caffeine. [7] Besides, it has successfully being employed as a green solvent in a number of effective organic reactions [8] for the preparation of significant compounds such as spirooxindole-pyran derivatives, [9] 1,4-benzothiazines, [10] bis(Indolyl)methanes, [11] polyfunctionalized alkenes, [12] quinoxalines, [13] 4(3H)-quinazolinones, [14] 2-pyrazoline derivatives [15] and enaminones. [16] For a long period, aromatic azo-compound has received considerable amount of interest among the chemists.…”

Humic acid: A Biodegradable Organocatalyst for Solvent‐free Synthesis of Bis(indolyl)methanes, Bis(pyrazolyl)methanes, Bis‐coumarins and Bis‐lawsones

“… [20] The widely used protocol to design this important molecule is very straightforward and it can easily obtained by the reaction between aldehydes and indole following the Friedel‐Craft alkylation type pathway. A few protocols are reported in literature using various catalyst and solvent such as enzymes, [21] meglumine, [22] thiamine hydrochloride, [23] graphene oxide, [24] ethyl lactate, [25] sulphated polyborate, [26] Lewis acids, [27–32] Brønsted acids, [33] heteropoly acids, [34–36] solid acids, [37–42] ionic liquids, [43] metal complexes, [44–46] 4‐sulfophthalic acid [47] and Iodine/tert‐Butyl Hydroperoxide [48] . Recently, a number of methodologies have been developed in this field [49–68] .…”

Convenient Synthesis and Biological Evaluation of Bis(indolyl)methane Alkaloid and Bis(aryl)alkanes Derivatives with Anti-cancer Properties

“…The indole scaffold and its derivatives are relevant and versatile structural nucleus in organic synthesis, in particular in many natural and biology medicine chemistry. [1][2][3] Bis(indolyl)methane derivatives (BIMs) are to be considered as very attractive motifs in numerous bioactive products, fine chemicals, especially in pharmaceutical chemistry (Figure 1). [4][5] BIMs as well as Bis(aryl)alkanes moieties show various types of biological and pharmacological activities, such as antibacterial, anti-inflammatory, 6 antiinfective, 7 and anti-cancer activities.…”

“…Even though these approaches have illustrated their convenience in the synthesis of BIMs, some drawbacks still limit their application, such as long reaction time, expensive or toxic metal ions, harsh acidity, high temperatures. 1,9 What's more, most of these synthetic accesses are the covalent C-C connection between Sp 2 -C of indoles or pyrroles and the acceptors, while few catalytic protocols of activation of primary amine to form covalent C-N bonds have been reported (Scheme 1). Therefore, a demand of milder, wider application and metal-free catalytic methods for obtaining various BIMs or Bis(aryl)alkanes derivatives is of great interest and importance.…”