Nucleophilic amination of methoxypyridines by a sodium hydride–iodide composite

Abstract

A new protocol for nucleophilic amination of methoxypyridines and their derivatives was developed using sodium hydride (NaH) in the presence of lithium iodide (LiI). The method offers a concise access to various aminopyridines which are potentially of medicinal interest.

Hydroalkylation of Styrenes with Benzylamines by Potassium Hydride

“…On the other hand, we recently discovered that sodium amide anions could be generated by the solvothermal deprotonation of aliphatic amines with sodium hydride (NaH) in the presence of dissolving iodide such as sodium iodide (NaI) or lithium iodide (LiI) and the resulting amide anions could undergo nucleophilic amination of methoxyarenes in both intra and intermolecular manners [27,28] . During this study, we also observed the equilibrium between the amide anion and the benzylic anion in the reaction of substrate 11 ( Scheme 5).…”

N‐Silylation of Amines Mediated by Et3SiH/KOtBu

“…When the reactions were carried out with NaO t Bu as base, no silylated products were produced, while NaH was found to be effective, although in low‐to‐moderate yields (see Table S1 in Supporting Information file). Interestingly, KH was also ineffective in producing silylated products and this point comes up for comment later in this article …”

“…This may initially seem curious, as commercial KH was not effective in promoting the reactions in the laboratory. However, a strong difference in reactivity between a free KH molecule and the commercial solid aggregate is expected …”

“…Interestingly, KH was also ineffective in producing silylated products and this point comes up for comment later in this article. [33][34][35] The conversion of the amines 1-4 to silyl derivatives as a function of time in the presence of KO t Bu (0.2 equiv. ), was monitored by 1 H-NMR.…”

Recent Progress in Amination Enabled by Transition-Metal-Free C(sp2)–O/C(sp2)–S Bond Cleavage Strategy

“…In 2018, Chiba and co-workers reported the amination of pyridyl methyl ethers using, again, the sodium hydride-iodide composite but at 60 °C (Scheme 4b). 20 Interestingly, unlike classical nucleophilic aromatic substitution, the amination took place not only at the paraor ortho-positions, but also at the meta-position to the pyridine nitrogen. This transformation proceeds through the S N Ar mechanism or the corresponding pyridyne intermediates.…”