Piperidine cyclopentanone

The only kinetic data reported are in a Ph.D. thesis (41). Integral order kinetics were usually not obtained for the reaction of a number of ketones with piperidine and a number of secondary amines with cyclohexanone. A few of the combinations studied (cyclopentanone plus piperidine, pyrrolidine, and 4-methylpiperidine, and N-methylpiperazine plus cyclohexanone) gave reactions which were close to first-order in each reactant. Relative rates were based on the time at which a 50% yield of water was evolved. For the cyclohexanone-piperidine system the half-time (txn) for the 3 1 ratio was 124 min and for the 1 3 ratio 121 min. It appears that an... 

Experimental evidence, obtained in protonation (3,6), acylation (1,4), and alkylation (1,4,7-9) reactions, always indicates a concurrence between electrophilic attack on the nitrogen atom and the -carbon atom in the enamine. Concerning the nucleophilic reactivity of the j3-carbon atom in enamines, Opitz and Griesinger (10) observed, in a study of salt formation, the following series of reactivities of the amine and carbonyl components pyrrolidine and hexamethylene imine s> piperidine > morpholine > cthyl-butylamine cyclopentanone s> cycloheptanone cyclooctanone > cyclohexanone monosubstituted acetaldehyde > disubstituted acetaldehyde. 

Reaction of the morpholine or piperidine enamine of cyclopentanone, however, gives an unstable adduct which rearranges under the reaction conditions and an aqueous work-up to give the ring expanded ketone 2-chloro-2-cyclohexen-l-one (203) (138,139). 

The formation of bicyclic imines (263,264) from piperidine enamines and y-bromopropyl amines may appear at first sight to be a simple extension of the reactions of enamines with alkyl halides. However, evidence has been found that the products are formed by an initial enamine exchange, followed by an intramolecular enamine alkylation. Thus y-bromodiethylamino-propane does not react with piperidinocyclohexene under conditions suitable for the corresponding primary amine. Furthermore, the enamine of cyclopentanone, but not that of cyclohexanone, requires a secondary rather than primary y-bromopropylamine, presumably because of the less favorable imine to enamine conversion in this instance. 

The reactions of dichlorocarbene with morpholine and piperidine enamines derived from cyclopentanone and cyclohexanone have been reported to lead to ring expanded and a-chloromethylene ketone products (355,356). Similarly a-chloro-a, -unsaturated aldehydes were obtained from aldehyde derived enamines (357). Synthesis of aminocyclopropanes (353,359) could be realized by the addition of diphenyldiazomethane (360) and the methylene iodide-zinc reagent to enamines (367). 

A new piperidine alkaloid Adalinine 352 was prepared in racemic form, using a rearrangement as a key step (equation 134). Enolate chemistry allowed double a-alkylation of cyclopentanone, producing 350 after oxime formation. Rearrangement provided a clear conversion into the lactam 351, easily converted to racemic Adalinine 352. 

An earlier synthesis of the piperidine alkaloid anhydronupharamine by Beckmann rearrangement of a cyclopentanone derivative has now been extended to... 

In the laboratory of J.D. White, the asymmetric total synthesis of the non-natural (+)-codelne was accomplished via intramolecular carbenoid insertion In the late stages of the total synthesis It was necessary to Install a 6-membered piperidine moiety. This transformation was accomplished utilizing a Beckmann rearrangement of the cyclopentanone oxime portion of one of the intermediates. Later the 6-membered lactam was reduced to the corresponding amine with LAH. To this end, an oxime brosylate (Bs) was prepared, which underwent a smooth Beckmann rearrangement in acetic acid to provide a 69% yield of two isomeric lactams in an 11 1 ratio in favor of the desired isomer. 

Mit befriedigenden Ergebnissen lassen sich neben Aceton und Phenyl-acetonen vor al-lem Cyclopentanone und Cyclohexanone umsetzen. Als Amin-Komponenten eignen sich Dimethyl- und Diathylamin sowie Pyrrolidine und Piperidine. 

There are occasional reports in the literature on the use of special reactions to form polyamides. One is a synthesis via enamines. In this case diisocyanates are condensed with cyclopentanone enamines of morpholine or piperidine ... 

Methyl oleate N,N,N, N -Tetramethylethylenediamine Triethylamine intermediate, rubber accelerators Allyl mercaptan t-Butylamine Diethylamine Isopropylamine 2-Methylpropanal p-Phenylenediamine Piperidine intermediate, rubber additives Benzoyl chloride intermediate, rubber antioxidants 2-Methylpropanal intermediate, rubber chemicals Benzonitrile Bisphenol A n-Butylamine Cyclopentanone Diethanolamine Ethylene carbonate Ethylenediamine Hexamethyleneimine dl-Limonene 2-Mercaptoethanol... 

Method Four, Fischer and Zempl n (313, 314). Piperidine N-ben-zoylpiperidine 8-benzpylvaleric acid a-bromo-8-benzoylamino-valeric acid -> o-amino-8-benzoylaminovaleric acid -> proline. The synthesis through the corresponding m-nitrobenzoyl derivatives was described by Fischer and Zempl (314). The preparation of o-bromo-8-benzoylaminovaleric acid (A) from cyclopentanone oxime throu the intermediates a-piperidone, 8-aminovaleric acid and 8-benzoylamino-vaieric acid has been reported by Schniq >p and Marvel (688). Mayeda and Nozoe (564) sjmthemzed (A) essentially by the method of Schniepp and Marvel. Copper prolinate dibydrate was prepared from (A). 

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