Using Calcium Carbide as an Acetylene Source for Cascade Synthesis of Pyrrolo[2,3‐b]quinoxalines via Copper‐Free Sonogashira Coupling Reaction

Abstract

A palladium‐catalyzed cascade protocol has been established for the synthesis of 4‐methyl‐1‐(1H‐pyrrolo[2,3‐b]‐quinoxalin‐2‐yl)cyclohexanols and 2‐phenyl‐1‐(1H‐pyrrolo[2,3‐b]quinoxalin‐2‐yl)propan‐1‐ols through the reaction of N‐alkyl(aryl)‐3‐chloroquinoxalin‐2‐amines with calcium carbide and cyclohexanones or 2‐phenylpropanal. This one‐pot process, carried out without any copper salt in the key step of the Sonogashira coupling reaction, provides an efficient method for the synthesis of 2,3‐disubstituted pyrrolo[2,3‐b]quinoxalines in the presence of catalytic amounts of Pd(PPh3)2Cl2 in DMSO/H2O with high yields. The benefit of this strategy is the use of a commercially available, inexpensive, and less hazardous primary chemical feedstock, calcium carbide, as an acetylene source in a wet solvent.

Calcium‐Based Sustainable Chemical Technologies for Total Carbon Recycling

“…Synthesis of pyrroloquinolines is also a multistep reaction. It begins with propargylamine formation and proceeds through Sonogashira coupling of propargylamine to an N ‐alkyl(aryl)‐3‐chloroquinoxaline‐2‐amine . Propargylamine forms first from calcium carbide and an aldehyde or ketone.…”

“…It begins with propargylamine formation and proceeds through Sonogashira coupling of propargylamine to an N-alkyl(aryl)-3-chloroquinoxaline-2-amine. [82] Propargylamine forms first from calcium carbidea nd an aldehyde or ketone. After palladium-catalyzed Sonogashira couplingo fp ropargylamine, the intermediate is cyclized to form the final product.…”

Acetylene in Organic Synthesis: Recent Progress and New Uses

“…A palladium-catalyzed cascade protocol for the synthesis of 4-methyl-1-(1 H -pyrrolo[2,3- b ]-quinoxalin-2-yl)cyclohexanols 119a and 2-phenyl-1-(1 H -pyrrolo[2,3- b ]quinoxalin-2-yl)propan-1-ols 119b from N -alkyl(aryl)-3-chloroquinoxalin-2-amines 117 , calcium carbide and cyclohexanones 118a or 2-phenylpropanal 118b has been developed [ 152 ].…”

“…The reactions were performed in the presence of catalytic amounts of Pd(PPh 3 ) 2 Cl 2 in a DMSO/H 2 O solvent mixture. This copper-free one-pot Sonogashira-type synthesis provided high yields of 2,3-disubstituted pyrrolo[2,3- b ]quinoxalines ( Scheme 65 )A proposed reaction mechanism [ 152 ] includes the following steps. Initially, calcium acetylide A is generated from CaC 2 and water.…”

Design, Synthesis, Antibacterial Evaluation and Molecular Docking Study of New 3‐Aminoquinoxaline‐2‐alkynyl Carboxylate Esters

“…Due to the special biological importance of quinoxalines, it is interesting to design and synthesize new potent and broadspectrum antibacterial quinoxalines. In continuation of our interest in the synthesis of organic compounds through palladium-catalyzed reactions, [25][26][27][28][29][30][31] new derivatives of 3-(3-(aminoquinoxalin-2-yl)prop-2-yn-1-yl carboxylate have been synthesized via a multi-component reaction catalyzed by Pd (PPh 3 ) 2 Cl 2 to find new antibacterial compounds.…”