Efficient synthesis and characterization of novel bis‐heterocyclic derivatives and benzo‐fused macrocycles containing oxazolone or imidazolone subunits

Abstract

Bis(3‐(arylthiomethyl)benzaldehydes), linked to aliphatic spacers via ethers, were prepared and used as key synthons for the bis(2‐phenyloxazol‐5(4H)‐ones) via their reaction with benzoylglycine in acetic anhydride in the presence of fused sodium acetate at 100°C for 6 hours. Bis(oxazol‐5(4H)‐ones) were reacted with the appropriate aromatic or heterocyclic amines in glacial acetic acid in the presence of fused sodium acetate at 100°C for 24 hours to afford a novel series of bis(2‐phenylimidazol‐4‐ones) and their related hybrids with benzo[d]thiazole and pyrimidine‐2,4(1H,3H)‐dione. Moreover, bis(oxazol‐5(4H)‐ones) reacted with (4‐aminobenzoyl)glycine to afford bis[(4‐(5‐oxo‐1H‐imidazol‐1‐yl)benzoyl)glycine] derivatives followed by their reaction with anisaldehyde in acetic anhydride containing fused sodium acetate at 100°C for 12 hours to afford bis(5‐oxo‐1H‐imidazol‐1‐yloxazol‐5(4H)‐one) hybrids. Furthermore, bis(3‐(arylthiomethyl)benzaldehydes) were reacted with 2,2′‐(terephthaloylbis(azanediyl))diacetic acid in acetic anhydride containing fused sodium acetate at 100°C for 12 hours to give benzo‐fused macrocycles containing oxazolone subunits which reacted with appropriate aromatic amines in DMF and glacial acetic acid containing fused sodium acetate at 100°C for 24 hours to give benzo‐fused macrocycles containing imidazolone subunits.

Salicylaldehydes Derived from 5-Chloromethyl-2-hydroxybenzaldehyde – Synthesis and Reactions

“…While this study was underway, a report that described the synthesis of several 5-[(arylthio)methyl]salicylaldehydes using KOH in ethanol at reflux temperature became publicly available. 27 A few attempts at replicating the published procedure using 4-chlorothiophenol as the sulfur nucleophile showed that it was not entirely reliable, as it sometimes (but not always) produced mixtures of reaction products from which the desired compound could no longer be isolated in pure form even after repeated recrystallization. Analysis of the mixture of reaction products by NMR indicated that at least two impurities were also phenolic aldehydes, which were presumably generated through the concurrent selfcondensation via O-alkylation of the starting aldehyde 2 under the reaction conditions, 36 possibly followed by replacement of the terminal chlorine atom in the resulting dimer of 5-(chloromethyl)salicylaldehyde by one of present nucleophiles (4-chlorothiophenol, or ethanol, or water).…”

Zeolite (Y‐H)‐based green synthesis, antimicrobial activity, and molecular docking studies of imidazole bearing oxydibenzene hybrid molecules

“…First, the cyclo‐condensation reaction of benzoglycine ( I ) with acetic anhydride formed azlactone ( III ), which was further reacted with substituted benzaldehydes to form 4‐aryl‐2‐phenyloxazol‐5(4 H )‐one ( 3a‐i ). The ring‐opening reaction of arylidene ( 3a‐i ) with 3‐phenoxybenzohydrazide in the presence of zeolite (Y‐H) may proceed through carbonyl activation to form open intermediate IV , which is further cyclized by eliminating water molecule for the generation of targeted N ‐(4‐benzylidene‐5‐oxo‐2‐phenyl‐4,5‐dihydro‐1 H ‐imidazol‐1‐yl)‐3‐phenoxybenzamides ( 4a‐i )[17,18].…”

Effective synthesis of new benzo‐fused macrocyclic and thiamacrocyclic dilactams and related pyrazolo‐fused macrocycles

“…To begin our study, bis(aldehydes) 5 , linked to aliphatic spacers via phenoxy linkage, were prepared and taken as versatile building blocks for the synthesis of the target macrocycles. Therefore, one equivalent of each of benzenethiol derivatives 1a,b , 5‐(chloromethyl)‐2‐hydroxybenzaldehyde 2 [52] and potassium hydroxide were allowed to react in ethanol at reflux for 3 h to afford the corresponding salicylaldehyde derivatives 3a,b in 88%–91% yields [53,54]. Next, the bis‐alkylation of the previous salicylaldehydes afforded the precursors 5 .…”

“…Thus, two equivalents of 3a,b were reacted with one equivalent of the appropriate 1,ω‐dibromoalkanes 4 in N , N ‐dimethylformamide (DMF) in the presence of anhydrous potassium carbonate. The prior mixture was stirred at room temperature (rt) for 8 h to afford the corresponding bis(aldehydes) 5 in 84%–87% yields (see Scheme 1 and Experimental section) [54].…”