Development of a One-Pot Synthetic Method for Multifunctional Oxazole Derivatives Using Isocyanide Dichloride

Abstract

A one-pot synthetic method was developed for multifunctional dihydrooxazole and oxazole derivatives. New reaction sequences were developed involving the formation of isocyanide dichloride, an aldol-type reaction with aldehydes, and a nucleophilic addition-elimination reaction, which efficiently afforded the dihydrooxazole and oxazole scaffolds.

A modified approach for the synthesis of biologically relevant 5-substituted-2-N-aryl-1,3-oxazole derivatives in mild conditions

“…The resulting solid was recrystallized from ethanol to obtain the titled compound 3a as white solid in 96% yield (227 mg). The melting point (170-172°C) and the spectral details of the product were found to be matching with the reported values [21].…”

Synthesis of 2,4,5-Trisubstituted Oxazoles with Complementary Regioselectivity from α-Oxoketene Dithioacetals and β-(Methylthio)-β-(het)aryl-2-propenones

“…Oxazole derivatives have also found applications in functional materials, as efficient luminophores for liquids and plastic scintillators, fluorescent probes for biological systems, corrosion inhibitors, components of laser dyes, sensors, receptors, polymers, and ligands for catalysis . This has generated considerable interest in the synthesis of this class of heterocycles in recent years with the development of several efficient synthetic methods. − …”

“…The classical methods for oxazole synthesis include cyclization of acyclic precursors, transition metal catalyzed coupling of prefunctionalized oxazoles, and dehydrogenation/dehydroelimination of oxazolines. , Cyclization approaches are much more effective due to diversity of the substrates, among which, Robinson–Gabriel condensation using α-acylaminoketones and its modified versions, ,, have been frequently utilized earlier to prepare a range of highly substituted oxazoles. However, this method requires the use of Bronsted or Lewis acid catalysts/reagents, which limits the overall functional group tolerance of the transformation.…”

Mechanistic Pathways in Amide Activation: Flexible Synthesis of Oxazoles and Imidazoles

“…3 As a result of this central role, a vast number of approaches and synthetic routes for the formation of both oxazoles and imidazoles have been reported. 4−6 …”

“… Oxazoles are known for their use as nonsteroidal anti-inflammatory drugs, PPAR modulators, hypoglycemics, and antibacterial agents, while imidazoles play important therapeutic roles, for example as antifungals, proton pump inhibitors, angiotensin inhibitors, and kinase inhibitors . As a result of this central role, a vast number of approaches and synthetic routes for the formation of both oxazoles and imidazoles have been reported. − …”