Chichibabin reaction

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

The Chichibabin reaction is a method for producing 2-aminopyridine derivatives by the reaction of pyridine with sodium amide. It was reported by Aleksei Chichibabin in 1914.

The direct amination of pyridine with sodium amide takes place in liquid ammonia. Following the addition elimination mechanism first a nucleophilic NH₂^- is added while a hydride (H^-) is leaving.

Before the Chichibabin reaction, only electrophilic substitution on the pyridine ring was possible, which is difficult due to the fact that pyridine is an electron-poor aromatic compound and additionally forms positive charged pyridinum ions, which further decrease the probability of an electrophile attack. The positions in the pyridine system attacked by the electrophiles are the 3rd and the 5th position.

The Chichibabin reaction is a nucleophilic substitution on the pyridine ring; the 2nd and 6th positions are therefore favoured over the other positions.

See also

• Amination

References

• A. E. Chichibabin and O. A. Zeide (1914). Zhur. Russ. Fiz. Khim. Obshch (J. Russ. Phys. Chem. Soc.). 46: 1212.
• A F Pozharskii, A M Simonov, V N Doron'kin (1978). "Advances in the Study of the Chichibabin Reaction". RUSS CHEM REV. 47 (11): 1042–1060. doi:10.1070/RC1978v047n11ABEH002292.CS1 maint: Multiple names: authors list (link)
• R. Norris Shreve, E. H. Riechers, Harry Rubenkoenig, and A. H. Goodman (1940). "Amination in the Heterocyclic Series By Sodium Amide". Industrial & Engineering Chemistry. 32 (2): 173–178. doi:10.1021/ie50362a008.CS1 maint: Multiple names: authors list (link)
• FW Bergstrom, HG Sturz, HW Tracy (1946). "The Use of the Fused Eutectic of Sodium amide and Potassium amide in Organic Synthesis". The Journal of Organic Chemistry. 11 (3): 239–246. doi:10.1021/jo01173a005.CS1 maint: Multiple names: authors list (link)