Studies in Piperidone Chemistry. I. A Synthesis of 5-Homopiperazinones

Abstract

The extension of either the well-known Schmidt reaction (1) or the Beckmann rearrangement (2) to 4-piperidones or their oximes should result in the synthesis of 5-homopiperazinones.Triacetonamine or 2,2,6,6-tetramethyl-4-piperidone (I) was prepared from phorone by the procedure described by Guareschi (3). When the amino ketone, I, was treated with hydrazoic and sulfuric acids, 2,2,7,7-tetramethyl-5-homopiperazinone (II) was formed in a yield of 88%. The following equation illustrates this and subsequent Schmidt reactions:

New 7‐membered diazepanone alkoxyamines for nitroxide‐mediated radical polymerization

“…Few reports on ring enlargements of sterically hindered piperidine‐4‐ones into their corresponding diazepinones have been published in the older literature. Thus, 2,2,6,6‐tetramethylpiperidin‐4‐one was expanded via the Schmidt reaction24 with hydrazoic acid or by way of the Beckmann rearrangement25 of its oxime tosylate adsorbed on aluminum oxide. This mild reaction was also successful for the rearrangement of the corresponding nitroxide.…”

Synthesis, Reactions, and Antimicrobial activity of N-Hydroxy-triacetonamine Derivatives

“…Although separation of compound (6) was done accidently, but it is expected. Ring expansion of piperidine derivative while reaction with sodium azide is reported[23].The Infrared spectrum of compounds (5) and (6) show characteristic absorption band for azide group. Also, the IR spectrum of compound (6) show absorption band for carbonyl group of amide.…”

Toward the Scale-Up of a Bicyclic Homopiperazine via Schmidt Rearrangement and Photochemical Oxaziridine Rearrangement in Continuous-Flow

“…Despite the important biological activities of fused diazepines, the homopiperazine ring system is somewhat under-represented in drugs, in part because of the absence of general or scalable methods for its synthesis. Ring expansion by nitrogen insertion of more readily accessible six-membered rings is a commonly used strategy. , The manufacture of ε-caprolactam, the key precursor for Nylon-6, involves a ring expansion via Beckmann rearrangement of cyclohexanone oxime and highlights an important industrial application of this approach . The related Schmidt rearrangement converts cyclic ketones to ring-expanded lactams using hydrazoic acid (HN 3 ) generated in situ from sodium azide and a strong acid (Scheme ).…”