Rapid, metal-free and aqueous synthesis of imidazo[1,2-a]pyridine under ambient conditions

Abstract

A route to access the privileged imidazo[1,2-a]pyridine scaffold in one step, 1–10 minutes using only aqueous NaOH, is reported.

Simple and Versatile Laboratory Scale CSTR for Multiphasic Continuous-Flow Chemistry and Long Residence Times

“…Our group recently reported a rapid, NaOH-promoted cycloisomerization reaction of several Nalkynylated 2-aminopyridinium bromides under aqueous conditions. 32 The pyridinium halides are cyclized instantaneously upon contact with base, producing the imidazopyridine products as water-insoluble oils during reaction. While this simplifies product recovery in batch, we speculated that such a rapid reaction would naturally suit a continuous-flow mode to boost space-time-yield.…”

“…Propargylpyridinium bromide was prepared as previously reported. 32 Deuterated CDCl 3 and D 2 O were used as supplied. 1 H and 13 C NMR spectra were recorded on either a Bruker DPX300 (300/75 MHz) spectrometer or a Bruker AV3-400 (400/100 MHz) spectrometer using the residual solvent as an internal standard.…”

Synthesis of 2‐Carbonylimidazo[1,2‐a]pyridines via Iodine–mediated Intramolecular Cyclization of 2‐Amino‐N‐propargylpyridinium Bromides

“…A variety of 2‐alkylimidazo[1,2‐ a ]pyridines ( 3a–m ) were prepared under aqueous conditions from 2‐amino‐1‐(prop‐2‐ynyl)pyridin‐1‐ium bromides in moderate to excellent (40‐97 %) yields (See supporting information). During the preparation of this manuscript, Nguyen group has also reported a base‐mediated synthesis of 2‐methylimidazo[1,2‐ a ]pyridines from corresponding 2‐amino‐1‐propargylpyridinium salts …”

“…On the other hand, in the absence of iodine 5‐exo‐dig hydroamination of 1 a followed by isomerization leads to the formation of 2‐methylimidazo[1,2‐ a ]pyridine ( 3 a ). Formation of 3 a from 1 a in the presence of base has also been proposed to proceed via alkyne‐allene isomerization of N ‐propargylpyridinium salts followed by cyclization …”

Deep Eutectic Solvent‐Mediated Regioselective Synthesis of Imidazoheterocycles

“…To date, the number of synthetic approaches for the synthesis of functionalized imidazoheterocycles has been reported. [ 15–18 ] The common methods for the preparation include coupling of 2‐halocarbonyls with 2‐aminopyridine derivatives. [ 19–22 ] The copper‐catalyzed multicomponent reaction of 2‐aminopyridine with acetylene and aldehyde has also been reported.…”