Ultrasound‐Assisted Green Synthesis of Pyrrole‐Fused Pyrimidine and Imidazole Rings through a Tandem Pseudo‐Four‐Component Reaction

Abstract

A new series of 1H‐pyrrolo[1,2‐a]imidazol‐6‐yl)acetamides and pyrrolo[1,2‐a]pyrimidin‐7‐yl)acetamides were synthesized by the ultrasound‐assisted tandem pseudo‐four‐component reaction (pseudo‐4CR). The present study reports the use of phenyglyoxal derivatives, malononitrile, 1,1‐bis(methylsulfanyl)‐2‐nitroethene, and diamines in EtOH as a green solvent to reach a product with excellent yields (85–95 %). Their structures were characterized by spectroscopic data (IR, MS, 1H, and 13C NMR) and verified by X‐ray analysis. The results revealed the influence of the electron‐withdrawing or electron‐donating substituent on the arylglyoxal ring and carbon chain length of the diamine on the formation of final product (pyrrole or pyridine ring). 1,2‐Diamines with arylglyoxal having electron‐withdrawing and electron‐donating substituent trigger the formation of the pyrrole and pyridine ring, respectively. However, 1,3‐diamines lead to only the formation of the pyrrole ring. This efficient and green protocol has remarkable advantages, such as abundant starting materials, simple operation, clean reaction profile, easy purification without traditional methods (i. e., column chromatography and crystallization), excellent tolerance to various substituents, and relatively short reaction time.

Simple and efficient synthesis of pyrrolo[3,2‐f]quinoxaline derivatives via three‐component reaction

“…After the successful utilization of dimedone, we next extended our investigation to cyclohexane-1,3-dione (3b). To our delight, cyclohexane-1,3-dione could also be successfully engaged in these MCRs and the corresponding pyrrolo[3,2-f]quinoxaline derivatives were provided with 72-90% yields (entries [13][14][15][16][17][18][19].…”

“…Recently, many research groups investigated the preparation of novel nitrogen-containing heterocycles by the reaction of the amines, arylglyoxals, and nucleophilic reagents through multicomponent reactions [17][18][19][20][21][22][23]. In 2020, we developed a three-component reaction of quinoxalin-6-amine, aldehyde, and 1,3-dicarbonyl compounds in EtOH solvent, yielding pyrazino[2,3-a]acridine derivatives [24].…”

Recent developments using malononitrile in ultrasound-assisted multicomponent synthesis of heterocycles

“…The structure of 2-cyano-2-(8-nitro-6-phenyl-1,2,3,4-tetrahydropyrrolo[1,2- a ]pyrimidin-7-yl)acetamide was characterized and verified by X-ray analysis. This efficient and green protocol has remarkable advantages, such as abundant starting materials, simple operation, clean reaction profile, easy purification without traditional methods (column chromatography and crystallization), excellent tolerance to various substituents, and relatively short reaction time [75] .

Scheme 14 Synthesis of imidazo[1,2-a]pyridine-6-carbonitrile derivatives.

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