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The Hofmann–Löffler reaction (also referred to as Hofmann–Löffler–Freytag reaction, Löffler–Freytag reaction, Löffler–Hofmann reaction, as well as Löffler's method) is an organic reaction in which a cyclic amine 2 (pyrrolidine or, in some cases, piperidine) is generated by thermal or photochemical decomposition of ''N''-halogenated amine 1 in the presence of a strong acid (concentrated sulfuric acid or concentrated CF3CO2H). The Hofmann–Löffler–Freytag reaction proceeds via an intramolecular hydrogen atom transfer to a nitrogen-centered radical and is an example of a remote intramolecular free radical C–H functionalization. center ==Historical perspective== In 1878, the structure of piperidine was still unknown, and A. W. Hofmann made attempts to add hydrogen chloride or bromine to it in the belief that the compound possessed unsaturation (i.e. he performed standard alkene classification test reactions). In the course of his studies, A.W. Hofmann synthesized a number of ''N''-haloamines and ''N''-haloamides and investigated their reactions under acidic and basic conditions. He reported that the treatment of 1-bromo-2-propylpiperidine 3 with hot sulfuric acid, followed by basic work-up, resulted in the formation of a tertiary amine, which was later shown to be δ-coneceine 4. center Although the Hofmann–Löffler–Freytag reaction was to become a general and expeditious process for the formation of pyrrolidines, it was not until about 25 years after Hofmann's work that further examples of the reaction appeared in the literature. In 1909, K. Löffler and C. Freytag extended the scope of this transformation to simple secondary amines and demonstrated the synthetic utility of the process as exemplified by their elegant synthesis of nicotine 6 from ''N''-bromo-''N''-methyl-4-(pyridin-3-yl)butan-1-amine 5. center 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「Hofmann–Löffler reaction」の詳細全文を読む スポンサード リンク
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