General Multicomponent Strategy for the Synthesis of 2‐Amino‐1,4‐diazaheterocycles: Scope, Limitations, and Utility

Abstract

Multicomponent reactions of primary 1,2‐ and 1,3‐diamines with carbonyl compounds and isocyanides resulting in the formation of diverse 2‐amino‐1,4‐diazaheterocycles are described. Lewis acids (LAs) promote the reactions effectively, and chlorotrimethylsilane (TMSCl) has been found to be a promoter of choice. The scope and limitations of the reactions with regard to each of the components are evaluated and discussed. Post‐IMCR modifications of the synthesized heterocycles have been elaborated.

One-pot synthesis of tetracyclic fused imidazo[1,2-a]pyridines via a three-component reaction

“…It is noteworthy that there was no report on a ketone-involving GBB reaction, and several attempts to explore the GBB reaction utilizing ketones as carbonyl reactant failed [ 27 , 37 ]. These difficulties could be partially explained in terms of the electronic and steric effect of the ketone involved.…”

Aminoazole-Based Diversity-Oriented Synthesis of Heterocycles

“…The most studied ones are the processes involving 3-amino-1,2,4-triazoles (Bienaymé and Bouzid, 1998 ; Tyagi et al, 2012 ; Urich et al, 2013 ; Aouali et al, 2015 ), 2-amino(benzo)thiazoles (Bienaymé and Bouzid, 1998 ; Guchhait and Madaan, 2009 , 2010 ; Guchhait et al, 2009 ; Al-Tel et al, 2010 ; Akritopoulou-Zanze et al, 2011 ; Baviskar et al, 2011 ; Burchak et al, 2011 ; Hieke et al, 2012 ; Tyagi et al, 2012 ; Vidyacharan et al, 2014 ; Martinez-Ariza et al, 2015 ; Ansari et al, 2016 ; Shaabani and Hooshmand, 2016 ; Shao et al, 2017 ), 2-amino-1,3,4-thiadiazoles (Krasavin et al, 2008 ; Guchhait and Madaan, 2009 ; Guchhait et al, 2009 ; Wadhwa et al, 2015 ), 2-amino(benz)imidazoles (Lee et al, 2013 ; Pereshivko et al, 2013 ). GBB-3CR involving 2-aminooxazoles (Bienaymé and Bouzid, 1998 ) led to the formation of imidazoazoles while involving 1,2,5-oxadiazole-3,4-diamine (Kysil et al, 2010 ) gave oxadiazolopyrazines. Groebke condensations of 5-aminopyrazoles (5-amino-3-methylpyrazole, 5-aminopyrazole-4-carbonitrile, ethyl 5-aminopyrazole-4-carboxylate) are described in the following publications (Bienaymé and Bouzid, 1998 ; Guchhait and Madaan, 2009 ; Guchhait et al, 2009 ; Baviskar et al, 2011 ; Rahmati and Kouzehrash, 2011 ; Rahmati et al, 2013 ; Demjén et al, 2014 ; Murlykina et al, 2017 ).…”

o-Aminothiophenol in Reactions with Carbonyl Compounds and Isocyanides: A Word of Caution

“…Although in our hands, the outcome of this reaction was similar to the one presented in Scheme 3, we decided to test it under TMSCl-promoted conditions 2. …”

“…Recently, we reported 1 on a new variant of an isocyanide-based multicomponent reaction (IMCR) of ophenylenediamines with aldehydes and isocyanides leading to easily oxidized dihydroquinoxalines and, ultimately, providing a conceptually new route to quinoxalines (Scheme 1). 1 This methodology has been recently extended by Kysil et al 2 to include cyclic ketone components as well as [1,2,5]oxadiazole-3,4-diamine under reaction conditions including TMSCl as the promoter. In addition, similar reactions involving 1,2-diamines have also been published.…”