Synthesis of Unexpected Pyrrolo[2,3-b]quinoxaline-2-carbaldehydes via Sonogashira Coupling Reaction

Abstract

The reaction of a number of N-alkyl-3-chloroquinoxaline-2-amines with propargyl bromide in the presence of PdCl 2 (PPh 3 ) 2 and copper(I) iodide in wet morpholine leads to the formation of the unexpected N-substituted pyrrolo[2,3-b]quinoxaline-2-carbaldehydes in good yields. A possible mechanism for the conversion is suggested.

Rapid Synthesis of 2‐Alkanol‐substituted Pyrrolo[2,3‐b]quinoxalines from Propargylic Alcohols via Copper‐free Sonogashira Coupling Reaction at Room Temperature

“…We have previously reported the synthesis of pyrrolo[2,3‐ b ]quinoxalines‐2‐carbaldehydes and their acetyl analogs from the reaction of N ‐alkyl‐3‐chloroquinoxaline‐2‐amines with propargyl bromide , or acetylenic alcohols , in the presence of palladium and copper catalysts in morpholine, as the solvent, at 70°C (Scheme ). In these conditions, unexpectedly, oxidation took place, and formyl/acetyl derivatives were formed.…”

“…With the optimized reaction conditions in hand (Table , entry 8), we evaluated the generality of the reaction protocol. A variety of N ‐alkyl‐3‐chloroquinoxaline‐2‐amines 1a – 1f was prepared [27a, 28] and then reacted with propargylic alcohols 2a – c in the presence of catalytic amounts of Pd(PPh 3 ) 2 Cl 2 and morpholine, as a base, in MeCN at room temperature to form 2‐alkanol‐substituted pyrrolo[2,3‐ b ]quinoxalines 3a – 3l in high yields. The results obtained were tabulated in Table .…”

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

“…Pyrroloquinoxalines have been extensively studied as bioactive compounds, and many of them are known to be biologically and medicinally useful molecules such as anti‐HIV agents, anti‐malarial agents, antagonist agents, anti‐cancer agents, and PARP‐1 inhibitors . Recently, we have reported the synthesis of pyrrolo[2,3‐ b ]quinoxaline derivatives by the Sonogashira coupling reaction of N ‐alkyl‐3‐chloroquinoxalin‐2‐amines with terminal alkynes, propargyl bromide, and propargyl alcohols, followed by the subsequent cyclization in a one‐pot process. In this work, we attempted to make this overall approach more attractive synthetically using calcium carbide as an acetylene source for the preparation of pyrrolo[2,3‐ b ]quinoxalines.…”

Pd/C-catalyzed, copper-free Sonogashira coupling: one-pot synthesis of 1-aryl-4-(2-phenylethynyl)[1,2,4]triazolo[4,3-a]quinoxalines in water

“…Recently, our group has prepared pyrrolo[2,3- b ]quinoxaline derivatives under mild conditions in one-pot reactions catalyzed by Pd–Cu [ 38 – 40 ]. We attempted to make this overall approach more attractive synthetically by examining the preparation of triazolo[4,3- a ]quinoxalines using a one-pot reaction of 2,3-dichloroquinoxaline, hydrazine, aldehydes, bromine, and phenylacetylene catalyzed by Pd/C without the use of copper as a co-catalyst in water.…”