Metal-free, efficient hydrazination of imidazo[1,2-a]pyridine with diethyl azodicarboxylate in neutral media

Abstract

The first example of metal-free regioselective hydrazination of imidazo[1,2-a]pyridine with diethyl azodicarboxylate was accomplished. This procedure is chemically appealing due to the high degree of functional group tolerance and efficiency in expanding molecule diversity.

Use of Imidazo[1,2‐a]pyridine as a Carbonyl Surrogate in a Mannich‐Like, Catalyst Free, One‐Pot Reaction

“…As part of our continued efforts to develop C‐C and C‐N bond formation reactions, particularly with imidazopyridines,, , we investigated the use of a Mannich‐like reaction for C‐3 aminomethylation of imidazo[1,2‐ a ]pyridines. Previously, the Mannich reaction has served as a tool to functionalize electron dense heterocycles and phenols using formaldehyde as a methylene source via acid catalyzed alkyl‐amination .…”

Organopromoted direct synthesis of 6-iodo-3-methylthioimidazo[1,2-a]pyridines via convergent integration of three self-sorting domino sequences

“…9 More recently, the hydrazination of such compounds with diethyl azodicarboxylate in the absence of metal catalysts was described (Scheme 1c). 10 As well, the regioselective C-3 sulfenylation of imidazo[1,2-a]pyridines has been achieved with various sulfenylating reagents, 11 including disulfides, thiophenols, 35 sodium sulfinates and sulfonyl hydrazides (Scheme 1d). In addition, methylthiolation using a DMSO-POCl 3 complex has been demonstrated (Scheme 1e).…”

“…5 provided 3aa in 87% yield (Table 1, entry 6), whereas further decreases in the charge of NH 2 CN resulted in significant decreases in the yields (Table 1, entries 3-5). Accordingly, various amines and other bases were also evaluated, but none had a positive impact on the outcome of the reaction (see Supporting 10 Information). These results indicated that NH 2 CN is an important mediator in this transformation.…”

“…When the reaction was carried out without acetophenone, 5-iodopyridin-2-amine (D) was 10 isolated in 93% yield (Scheme 4a). The use of D as the substrate instead of 2-aminopyridine under the standard conditions led to the formation of 6-iodo-3-(methylthio)-2-phenylimidazo[1,2a]pyridine (3aa) in 78% yield (Scheme 4b), indicating that D is an important intermediate in this transformation.…”

“…Further studies to elucidate a detailed mechanism and identify applications of this protocol are currently underway in our laboratory. 10 This work was supported by the National Natural Science Foundation of China (Grant Nos. 21272085 and 21472056).…”