Continuous multistep synthesis of 2-(azidomethyl)oxazoles

Abstract

An efficient three-step protocol was developed to produce 2-(azidomethyl)oxazoles from vinyl azides in a continuous-flow process. The general synthetic strategy involves a thermolysis of vinyl azides to generate azirines, which react with bromoacetyl bromide to provide 2-(bromomethyl)oxazoles. The latter compounds are versatile building blocks for nucleophilic displacement reactions as demonstrated by their subsequent treatment with NaN3 in aqueous medium to give azido oxazoles in good selectivity. Process integration enabled the synthesis of this useful moiety in short overall residence times (7 to 9 min) and in good overall yields.

Multi‐Step Continuous‐Flow Organic Synthesis: Opportunities and Challenges

“…Therefore, methods or techniques for its safe and efficient syn- thesis has always been in demandb yt he industry.K appe and co-workersu sed vinyl azide as ar aw material to efficiently and safely synthesize 2-(azidomethyl) oxazoles in three steps. [7] The authorso ptimized each step in af low system andi solated 2-(azidomethyl)oxazole 15 in 50-60 %y ield in less than 10 min ( Figure 5).…”

A sustainable strategy for the straightforward preparation of 2H-azirines and highly functionalized NH-aziridines from vinyl azides using a single solvent flow-batch approach

“…Similarly, Maurya developed a microfluidic photoreactor for the synthesis of a fused β-carboline from an α-ketovinyl azide and a 1,2,3,4-tetrahydro-β-carboline ( Scheme 1b ) [ 30 ]. More recently, Kappe reported the generation of 2 H -azirines under continuous flow conditions, and their transformation into functionalized oxazoles using acetone as the solvent ( Scheme 1c ) [ 28 ]. Inspired by these recent reports, we became interested in the development of an eco-friendly strategy for the safe preparation of highly functionalized NH -aziridines from acyclic precursors.…”

Access to highly substituted oxazoles by the reaction of α-azidochalcone with potassium thiocyanate

“…In the recent past, the readily accessible 2H-azirine, an efficient source of nitrogen, was employed as starting material for the synthesis of oxazole with various coupling partners such as aldehyde, trifluoroacetic acid, etc. [8,[45][46][47][48][49][50] (Scheme 1). Thiazole is a common structural motif that is found in a wide variety of naturally existing alkaloids and a number of pharmaceutically active compounds [51][52][53].…”

“…In the recent past, the readily accessible 2 H -azirine, an efficient source of nitrogen, was employed as starting material for the synthesis of oxazole with various coupling partners such as aldehyde, trifluoroacetic acid, etc. [ 8 , 45 – 50 ] ( Scheme 1 ).…”