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The Chichibabin reaction (pronounced ' (chē')-chē-bā-bēn) 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 following is the overall form of the general reaction: 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. Ciganek describes an example of an intramolecular Chichibabin reaction in which a nitrile group on a fused ring is the source of nitrogen in amination. == Mechanism == It is widely accepted that the Chichibabin reaction mechanism is an addition-elimination reaction that proceeds through an σ-adduct (Meisenheimer adduct) intermediate (the third structure). First, the nucleophilic NH2− group adds to the δ+ ring carbon pushing electrons onto the ring nitrogen and forming the anionic σ-adduct, which is stabilized by sodium. Electrons from the nitrogen are then pushed towards the ring forming a C=N bond and kicking out a hydride ion. The hydride ion abstracts a hydrogen from the positively charged nitrogen, forming hydrogen gas. The ring nitrogen then pushes electrons back into the ring, regaining aromaticity, the now negatively charged NH group abstracts a proton from water giving us the product. Reaction progress can be measured by the formation of hydrogen gas and red color from σ-adduct formation.〔 Sodium amide is a handy reagent for the Chichibabin reaction but handling it can be dangerous and caution is advised. * σ-adduct (Meisenheimer adduct) formation Evidence indicates that before addition of the amino group, the ring nitrogen is sorbed onto the surface of sodium amide and the sodium cation forms a coordination complex.〔 This increases the δ+ on the α-carbon, thus 1,2-addition of sodium amide is favored over 1,4-addition. The proximity of the amino group to the α-carbon once the coordination complex is formed also makes the 1,2-addition more likely to occur. Some data exists that supports a single electron transfer as the proposed pathway for σ-adduct formation.〔 In most cases, the anionic σ-adduct is unstable making its formation the rate determining step.〔 * Hydride ion elimination In addition to the mechanism shown above, other pathways have been proposed for the elimination step.〔 The mechanism above, loss of the hydride ion followed by abstraction of a proton, is supported by the fact that the nucleophile needs at least one hydrogen atom for the reaction to proceed. Another competing pathway could be the elimination of hydride by sodium to form sodium hydride. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Chichibabin reaction」の詳細全文を読む スポンサード リンク
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