Copper-Catalyzed One-Pot Synthesis of Quinazolinones from 2-Nitrobenzaldehydes with Aldehydes: Application toward the Synthesis of Natural Products

Abstract

A novel, efficient, and atom-economical approach for the construction of quinazolinones from 2-nitrobenzaldehydes has been unveiled via copper-catalyzed nitrile formation, hydrolysis, and reduction in one pot for the first time. In this reaction, urea is used as a source of nitrogen for nitrile formation, hydrazine hydrate is used for both the reduction of the nitro group and the hydrolysis of nitrile, and atmospheric oxygen is used as the sole oxidant. The method portrays a wide substrate scope with good functional group tolerances. Moreover, this method was applied for the synthesis of schizocommunin, tryptanthrin, phaitanthrin-A, phaitanthrin-B, and 8H-quinazolino­[4,3-b]­quinazolin-8-one.

Access to Dihydroquinazolinones, spiro‐Quinazolinones and their Bioactive Molecular Scaffolds by Exploring the Unique Reactivity of 2‐Nitrobenzonitrile towards Cu‐Hydrazine Hydrate

“…Towards our continued interest in the construction of N‐heterocycles, [18] we recently explored a novel approach for the synthesis of quinazolonones under copper catalyzed condi‐tion [18b] . With encouragement from the previous work, we started exploring the reactivity of o/m/p‐nitro benzonitrile towards hydrazine hydrate in presence of the copper as a catalyst.…”

DDQ in mechanochemical C–N coupling reactions

“…Various methodologies are available in the literature toward constructing quinazolin-4(3 H )-one derivatives [ 40 , 45 – 46 ]. Quinazolin-4(3 H )-ones and its derivatives possess several biological activities such as antibacterial [ 47 ], antiviral [ 48 ], antitumor [ 49 – 50 ], antimalarial [ 51 ], anti-inflammatory [ 52 ], etc.…”

N-Carboxyanhydrides directly from amino acids and carbon dioxide and their tandem reactions to therapeutic alkaloids

“…When 1i , 5a , T3P, DIPEA, and DMAP were combined in a mixture of CH 3 CN/acetone (3 : 1) under CO 2 (Table S7†), the alkaloid 7 was identified as the primary product with only trace amounts of 6a . Although the linear synthesis of 7 starting from 2-aminobenzoic acid has not yet been reported, we estimated the overall yield for the sequence 1i → 2i → 6a → 7 (Scheme S1†) to be ∼60% based on the expected yields of the individual steps (89, 49 90, 17 and 77%, 50 respectively). Our isolated yield of 31% for 7 is moderate but because it was obtained from a one-pot tandem reaction, there are reductions in cost, time, labor, and waste compared to that of products obtained from the three-step reactions in Scheme S1 †.…”