An Efficient Method for the N-Bromosuccinimide Catalyzed Synthesis of Indolyl-Nitroalkanes

Abstract

An efficient and practical method for the synthesis of indolyl-nitroalkane derivatives catalyzed by N-bromosuccinimide is described. The generality of this method was demonstrated by synthesizing an array of diverse 3-substituted indole derivatives by the reaction of different β-nitrostyrenes with various substituted indoles. Simple reaction conditions accompanied by good yields of indolyl-nitroalkanes are the merits of this methodology.

Synthetic Approaches to 3-(2-Nitroalkyl) Indoles and Their Use to Access Tryptamines and Related Bioactive Compounds

“…Interaction of nitroalkenes with Lewis acids is by far the most exploited way of activation in their reaction with indoles. A suitable tuning of the Lewis acidity of the catalyst is possible so that a large variety of reaction conditions can be adopted for a successful FC process (Table ). − Among these catalysts, lanthanide salts have been proved to be rather efficient in promoting this reaction since their “hard” acidity make them particularly effective in the interaction with the negatively charged oxygen atoms of nitroalkenes.…”

The Trifluoromethyl Group as a Bioisosteric Replacement of the Aliphatic Nitro Group in CB1 Receptor Positive Allosteric Modulators

“…The reaction of an indole with nitrostyrene has been widely reported in the literature and there are a considerable range of methods available for this simple 1,4-conjugate addition reaction. [17][18][19][20][21][22][23][24] There is literature precedent for the nitro group to be replaced with a carboxylic acid in this series of compounds, which is achieved by initial reaction of an indole with the highlyelectron deficient diethylbenzylidene malonate. 21,22 The limited similarity of nitro group binding to carboxylic acid binding, in spite of the near perfect isosterism, has been discussed by Kelly and Kim.…”

“…[17][18][19][20][21][22][23][24] There is literature precedent for the nitro group to be replaced with a carboxylic acid in this series of compounds, which is achieved by initial reaction of an indole with the highlyelectron deficient diethylbenzylidene malonate. 21,22 The limited similarity of nitro group binding to carboxylic acid binding, in spite of the near perfect isosterism, has been discussed by Kelly and Kim. 25 A small range of derivatives can be accessed from the carboxylic acid (e.g.…”

“…Because of this strong electron-withdrawing nature, the presence of a nitro group also facilitates many chemical reactions; thus, it is often found in screening collections (including the collection from which AZ-4 was originally identified). The reaction of an indole with nitrostyrene has been widely reported in the literature, and there are a considerable range of methods available for this simple 1,4-conjugate addition reaction. − There are literature precedents for the nitro group to be replaced with a carboxylic acid in this series of compounds, which is achieved by initial reaction of an indole with the highly electron-deficient diethylbenzylidene malonate. , The limited similarity of nitro group binding to carboxylic acid binding in spite of the near-perfect isosterism has been discussed by Kelly and Kim . A small range of derivatives can be accessed from the carboxylic acid (for example, CH 2 OH, CO 2 H, CO 2 Et, CONHNH 2 , CONH 2 , and CONHMe, Figure ; see the Supporting Information); however, these were inactive as CB 1 PAMs.…”

Nano n-propylsulfonated γ-Fe2O3 (NPS-γ-Fe2O3) as a magnetically recyclable heterogeneous catalyst for the efficient synthesis of 2-indolyl-1-nitroalkanes and bis(indolyl)methanes

“…5 Incidentally, the polymerized products of indole derivatives involve troublesome isolation procedures to obtain the desired product. Many attempts have been made by organic chemists to circumvent this problem by using H 2 NSO 3 H, 6 ionic liquid-coordinated Yb(III) sulfonate, 7 Zn(OAc) 2 , 8 Al(DS) 3 , 9 I 2 , 10 H 3 PW 12 O 40 , 11 NBS 12 and microwave or ultrasound irradiation. 13 However, most of the reported methods suffer from one or more of the following drawbacks, such as using large amounts of solid supports or un-recyclable catalysts, which would eventually result in the generation of a large amount of toxic waste, moderate yields of the products, long reaction time and difficult work-up procedures.…”