Glacial acetic acid as an efficient catalyst for simple synthesis of dindolylmethanes

Abstract

Glacial acetic acid as a protic acid was employed as a catalyst in a solvent free condition for facile preparation of di(indolyl)methanes (DIMs) via one-pot condensation of indole with aryl or heteroaryl aldehydes. Various aryl and heteroaryl aldehydes were efficiently converted to the corresponding di(indolyl)methanes (1a-p) in high yields. The described novel synthetic method proposes several advantages of safety, mild condition, short reaction times, high yields, simplicity and the inexpensively glacial acetic acid compared to other catalysts.

Directly Bridging Indoles to 3,3′‐Bisindolylmethanes by Using Carboxylic Acids and Hydrosilanes under Mild Conditions

“…These observations suggested a feasible pathway involving Lewis acid‐mediated reduction of the carboxylic acid to the aldehyde and subsequent Friedel–Crafts reaction between the indole and aldehyde. In addition, carboxylic acid not only acts as a reactant, but also promotes the Friedel–Crafts reaction between the indole and aldehyde …”

“…[15] Furthermore, the amount of formic acid and hydrosilane werei nvestigated in detail, and the optimal amountsofformic acid and Et 3 SiH compared with 1a were 2a nd 4.5 equivalents, respectively (entries 4a nd [13][14][15]. Polar solventa cetonitrile was am ore suitable solvent (entry 4) compared with ethers and arenes (entries [16][17][18][19]. This solvent effect maybeattributed to the stability of the intermediate in the polar solvent.…”

Synthesis and antiproliferative activity of various novel indole Mannich bases

“…The preparation of condensation products from aldehydes (formaldehyde, acetaldehyde), indole and secondary or primary amines is usually carried out in glacial acetic acid [1][2][3][4][5] . We have now found that the same procedure can be easily applied to glutaraldehyde instead of formaldehyde.…”

“…The use of indole Mannich bases in organic synthesis has already led to important practical and basic results, contributing to the development of promising directions in the chemistry of indoles. The indole Mannich bases are well known indole derivatives in organic synthesis; it is of relevance both for obtaining a large group of endogenous substances, and for the synthesis of natural compounds and indole derivatives which possessing high biological activity [1][2][3][4][5] . Mannich reaction of indole and formaldehyde or acetaldehyde with several types of secondary and primary amines was published in 1937 [6] .…”

Indoles as anticancer agents

“…It entered clinics in the 1970s for the treatment of ovarian carcinoma but difficulties were encountered, as it was insoluble in water and thus is difficult to formulate. However, it has recently been recognised as a second-line treatment for ovarian carcinoma [12][13][14][15][16][17][18][19][102][103][104] . Schoentjes et al [105] reported a patent of indole derivatives with general formula (I) in 2011 and reported its use for the treatment of cancers ( Figure 11).…”