Synthesis and Characterization of Newly Fused 1,2-Dihydropyrido[3,4-b], Bridged Oxadiazol-2-yl, 4-Substituted-benzylidene Hydrazide and Arylidene 6-Chloroquinoxaline 1,4-Dioxides

Abstract

Some simple reactions using commercially available chemicals were used in the preparation of new biologically remarkable quinoxaline 1,4-dioxide derivatives. Several steps performed on 4-chloro-2-nitroaniline resulted in a quinoxaline 1,4-dioxide derivative, which reacted with dimethylformamide dimethylacetal (DMF-DMA) to produce an enamine. Transamination of this enamine with anilines gave the fused 1,2-dihydropyrido[3,4-b]quinoxaline 5,10-dioxide derivatives via an addition-elimination mechanism. Basic condensation reaction of quinoxaline active methyl afforded unexpected decarboxylated arylidene derivatives by using different aromatic aldehydes. Bridged oxadiazol-2-yl derivatives were obtained from the reaction of a hydrazide derivative with carbon disulfide and p-nitrobenzoic acid respectively. Whereas, acidic condensation of that hydrazide with aromatic aldehydes afforded the arylidene hydrazides.

Quinoxaline 1,4-Dioxides: Advances in Chemistry and Chemotherapeutic Drug Development

“…Similarly, enamine 34 was obtained from 2-carboethoxy-7-chloro-3-methylquinoxaline 1,4-dioxide and DMADMF [ 82 ]. The transamination of this derivative with morpholine gives enamine 35 , while the reaction with anilines is accompanied by cyclization to pyridin-2-ones, leading to the formation of derivatives 36a – c in good yields ( Scheme 11 ).…”

“…Azide 73 rearranges into 2-alkyl carbamates 74a-c or substituted ureas 75a-c when boiled in an alcohol or amine solution, respectively (Scheme 33) [120]. The transformations of the hydrazide of 3-methylquinoxaline-2-carboxylic acid 76, obtained from the corresponding ethyl ester and hydrazine, are applied to the functionalization of the quinoxaline 1,4-dioxide scaffold at position 2 [82]. Condensation of hydrazide 76 with benzaldehydes in the presence of acetic acid in ethanol gave hydrazones 77a and 77b (Scheme 34).…”

An appraisal on synthetic and pharmaceutical perspectives of quinoxaline 1,4‐di‐N‐oxide scaffold

“…In addition, a phase II clinical trial for the anticancer drug Tirapazamine (3‐amino‐1,2,4‐benzotriazine‐1,4 dioxide) was recently accomplished (Covens et al, 2006; Maluf et al, 2006). Even though QdNOs are still in the research stage, they have been shown to have a lot of therapeutic potential (Said et al, 2018).…”