Revisiting the Chichibabin Reaction: C2 Amination of Pyridines with a NaH−Iodide Composite

Pang, Jia; Kaga, Atsushi; Roediger, Sven; Lin, Min Htoo; Chiba, Shunsuke

doi:10.1002/ajoc.201900094

Cited by 17 publications

(6 citation statements)

References 20 publications

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“…2-Aminopyridine is synthesized by the reaction of pyridine with sodium amide (Chichibabin amination) [12]. It is obtained in high yield after the hydrolysis of the intermediate salt [13,14].…”

Section: Figure 1 Drug Molecular Structures With Aminopyridine Consti...mentioning

confidence: 99%

Syntheses, Complexation and Biological Activity of Aminopyridines: A Mini-Review

Orie¹,

Duru²,

Ngochindo³

2021

AJHC

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Aminopyridines are among the classes of heterocyclic compounds that have been extensively studied in the last few decades owing to their interesting biological activities. They exist in three isomeric forms: 2-aminopyridine, 3-aminopyridine and 4-aminopyridine. The diversity in their pharmacological activities has attracted the attention of many researchers to explore the reasons for their wide potential. This study examines recent advances related to the efficient procedure for synthesizing different types of aminopyridine derivatives, its coordination site with metals and biological activities using systematic literature review and content analysis. Other important concepts of aminopyridines discussed are basicity, electric hindrance as related to percentage yield of isomeric forms and spectra updates on the characterization of aminopyridines. The findings from this study also reveal the array of solvents used for purification processes; ideas on isomers that have not been used in the synthesis of aminopyridine derivatives and their respective biological activities. The significance of this study is on the various synthetic methods revealed, which may be helpful to the development of newer compounds with aminopyridines moieties that could offer high bioactivity and lesser toxicity.

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Section: Figure 1 Drug Molecular Structures With Aminopyridine Consti...mentioning

confidence: 99%

Syntheses, Complexation and Biological Activity of Aminopyridines: A Mini-Review

Orie¹,

Duru²,

Ngochindo³

2021

AJHC

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“…In the first strategy, the preformed 4,4′-bipy skeleton is directly functionalized but substitution is only possible at positions ortho with respect to the heteroatoms. The Chichibabin reaction is perhaps the most useful reaction because the resulting amine substituents are easily converted to other functional groups. Both 2,2′-diamino- and 2,2′,6,6′-tetraamino-4,4′-bipyridines have been obtained by means of this method .…”

Section: Introductionmentioning

confidence: 99%

“…In the first strategy, the preformed 4,4′-bipy skeleton is directly functionalized but substitution is only possible at positions ortho with respect to the heteroatoms. The Chichibabin reaction 14 diamino-and 2,2′,6,6′-tetraamino-4,4′-bipyridines have been obtained by means of this method. 15 The only other examples of the addition of four substituents to 4,4′-bipy are metalmediated (Fe(II) 16 or Ag(I) 17 ) radical additions of four acetyl substituents, although yields are low.…”

Section: ■ Introductionmentioning

confidence: 99%

Functionalized 4,4′-Bipyridines: Synthesis and 2D Organization on Highly Oriented Pyrolytic Graphite

et al. 2021

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Commercial 4,4′-bipyridine is a popular scaffold that is primarily employed as a linker in 3D self-assembled architectures such as metallo-organic frameworks or as a connector in 2D networks. The introduction of alkyl substituents on the bipyridine skeleton is instrumental when 4,4′bipyridines are used as linkers to form 2D self-assembled patterns on surfaces. Here, several synthetic strategies to access 4,4′-bipyridines functionalized at various positions are described. These easily scalable reactions have been used to introduce a range of alkyl substituents at positions 2 and 2′ or 3 and 3′ and at positions 2,2′ and 6,6′ in the case of tetra-functionalization. Scanning tunneling microscopy studies of molecular monolayers physisorbed at the graphite−solution interface revealed different supramolecular patterns whose motifs are primarily dictated by the nature and position of the alkyl chains.

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“…In fact, of the small-molecule-based therapetics that were approved by the FDA in 2019, 8 of 32 (25%) contained a 2-aminopyridine (5 of 32) or 2-aminodiazine (3 of 32) motif (for examples, see Figure ). Thus, given the importance of 2-aminopyridines, the challenges associated with pyridine N -oxide and related chemistry, and the extreme conditions and narrow utility of the Chichibabin reaction, we aimed to develop conditions for the direct conversion of pyridines to 2-aminopyridines that would be applicable toward the functionalization of drug-like molecules. Specifically, the target reaction would need to occur with exquisite site selectivity, work directly on pyridines without preactivation, be tolerant of the protic and Lewis basic functionalities found in drug-like molecules, be able to be conducted on the benchtop without special precautions toward air or moisture, generate minimal waste, allow for simple purification, and employ only simple and readily available reagents …”

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confidence: 99%

A Multifunctional Reagent Designed for the Site-Selective Amination of Pyridines

2020

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We report the development of a multifunctional reagent for the direct conversion of pyridines to Boc-protected 2aminopyridines with exquisite site-and chemoselectivity. The novel reagent was prepared on 200 gram-scale in a single step, reacts in the title reaction under mild conditions without precautions towards air or moisture, and is tolerant of nearly all common functionality. Experimental and in-situ spectroscopic monitoring techniques provide detailed insights and unexpected findings for the unique reaction mechanism.

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Revisiting the Chichibabin Reaction: C2 Amination of Pyridines with a NaH−Iodide Composite

Abstract: A NaH-iodide composite was found capable of mediating the Chichibabin amination under mild reaction conditions, allowing efficient access to a range of 2-aminopyridines and their derivatives.

Cited by 17 publications

References 20 publications

Syntheses, Complexation and Biological Activity of Aminopyridines: A Mini-Review

Syntheses, Complexation and Biological Activity of Aminopyridines: A Mini-Review

Functionalized 4,4′-Bipyridines: Synthesis and 2D Organization on Highly Oriented Pyrolytic Graphite

A Multifunctional Reagent Designed for the Site-Selective Amination of Pyridines

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