A Highly Flexible and Efficient Ugi-Type Multicomponent Synthesis of Versatile N-Fused Aminoimidazoles

Abstract

A microwave-promoted highly flexible and efficient Ugi-type multicomponent reaction of heterocyclic amidines with aldehydes and isocyanides catalyzed by zirconium(IV) chloride was developed. The general protocol offered the very reliable synthesis of a library of medicinally important, widely versatile N-fused aminoimidazoles in excellent yields. Poorly reactive heterocyclic amidines, functionally and sterically hindered aldehydes, which suffer as troublesome reactants in earlier described methods, were rendered as feasible substrates in this process. The efficient catalysis by ZrCl 4 in addition to the effect of microwave irradiation was found crucial for gaining superior flexibility and efficiency of the protocol.

Synthesis of imidazo[1, 2‐a]pyridines via the silver acetate‐catalyzed Groebke‐Blackburn‐Bienayme reaction with ethylene glycol as a biodegradable and sustainable solvent

“…Over the past two decades, significant advances have been achieved using the multicomponent reaction (MCR) for the synthesis of pharmaceuticals and natural products . The catalytic Groebke‐Blackburn‐Bienayme reaction (GBBR) is a synthetically useful MCR to establish the 3‐aminoimidazo‐fused heterocyclic scaffold by a one‐pot formation of the CN and CC bonds with good atomic economy .…”

“…Over the past two decades, significant advances have been achieved using the multicomponent reaction (MCR) for the synthesis of pharmaceuticals and natural products. [1][2][3] The catalytic Groebke-Blackburn-Bienayme reaction (GBBR) is a synthetically useful MCR to establish the 3-aminoimidazo-fused heterocyclic scaffold by a one-pot formation of the C N and C C bonds with good atomic economy. [4][5][6][7] This reaction has been widely used for the synthesis of bioactive compounds with a broad spectrum of pharmacological and biological applications, such as antiviral, antibacterial, fungicidal, and antiinflammatory properties.…”

A Comparative Study on the Groebke-Blackburn-Bienaymé Three-Component Reaction Catalyzed by Rare Earth Triflates under Microwave Heating

“…25 Also, GBB reactions catalyzed by heterogeneous catalysts such as succinyl-β-cyclodextrin, 26 calix [6]arene-SO 3 H surfactant, 27 multi-walled carbon nanotubes/H 2 SO 4 , 28 cellulose@Fe 2 O 3 nanoparticles (NPs), 29 and fluconazole modified silicacoated magnetite NPs (Fe 3 O 4 @SiO 2 -Flu) 30 were recently described. However, Lewis acids are the most widely used catalysts for this organic transformation; examples include InCl 3 , 31 BiCl 3 , 32,33 RuCl 3 , 34 FeCl 3 , 35 ZnCl 2 , 36 ZrCl 4 , 37,38 CeCl 3 .7H 2 O, 39 and LaCl 3 .7H 2 O, 40 among others.…”

Facile synthesis of 1H-imidazo[1,2-b]pyrazoles via a sequential one-pot synthetic approach

“…In the relevant literature [7,28–29 31–33], the products have predominantly been described as 5 H -imidazo[1,2- b ]pyrazoles with an endo double bond (and not as 1 H -imidazo[1,2- b ]pyrazoles), but without 2D NMR-based support. However, the GBB-3CR of functionalized pyrazoles might lead to the formation of two regioisomers [24] and four different tautomeric forms (5 H - or 1 H -imidazo[1,2- b ]pyrazole with an endo- or exocyclic double bond) of each regioisomer.…”