Piperideines

Tetrahydrocarboline derivatives have recently been synthesized from 2-o-nitroarylated cyclohexanone derivatives. Thus, reductive cyclization of 3-(2,4-dinitrophenyl)-l-methyl-4-piperidone (68) (prepared by the reaction of 2,4-dinitrochlorobenzene with l-methyl-4-A-pyrrolidmo-3-piperideine) gave 7-amino-2-methyl-l,2,3,4-tetrahydro-y-carboline (69). Neither catalytic nor chemical reduction of the... 

So far, only the ring system of ervitsine has been synthesized. Exploiting the regiospecific alkylation of a 2-cyano-3-piperideine derivative 279, Husson et al. (196) obtained 280, whose stereochemistry was determined by X-ray analysis (Scheme 5). 

Physicochemical properties of azines, 5, 69 of pyrroles. II, 383 3-Piperideines, 12, 43 Polyfluoroheleroaromatic compounds, 28, I Polymerization of pyrroles and indoles, acid-catalyzed, 2, 1... 

Few reports on the electrolytic reduction of pyridine mention the isolation of partially reduced products. The only one observed to date has been the 3-piperideine (5). Ferles attributed the presence of 5 to concurrent reduction mechanisms, one which led to this product and the other to piperidine (Scheme 2).3S Thus, if the first-formed intermediate was a 1,4-dihydro product, then full reduction to piperidine occurred, but if the intermediate was a 1,2-dihydro product, then the olefin was formed. The 3-piperideine (5) would not be further reduced under the conditions. The concept of competing pathways at an initial step in the reduction mechanism is probably sound, but the proposal of 1,2- versus 1,4-dihydro intermediates has not been fully substantiated. 

Ferles et al. have studied the reduction of alkylpyridines and reported the yields of piperidines and 3-piperideines. For instance, reduction of either 2-picoline (15) or 3-picoline (16) gave predominantly the respective piperidines it also gave significant amounts of the piperideines 17 and 18, respectively (Scheme 5) (Table I).3i Other isomeric piperideines were not formed, and the... 

Reduction of both the free bases and their quaternary salts proceeds by similar mechanisms. In pyridine and its quaternary salts, a hydride ion, or its equivalent, attacks a position of a low electron density, i.e. the 2- or 4-position. The mechanism of the reduction of quaternary salts of pyridine and its homologs (LukeS and Ferles414) has been elucidated using deuterated formic acid.415 The hydride ion attack in position 2 is followed by addition of a proton to the enamine grouping with the formation of A 3-piperideines (124). If the reduction commences with attack in the 4-position, a saturated base (125) is the final product. In agreement, a-picoline methobromide yields 1,2-dimethyl-... 

The conformational preferences in alkyl- and phenyl-substituted 3-piperideines (1,2,3,6-tetrahydropyridines) were theoretically calculated by ab initio and molecular mechanics calculations (01CEJ4715). A set of rules for the estimation of the position of conformational equilibria were derived that are very reliable as indicated by comparing the results with previous stereochemical assignments. 

The three possible tetrahydropyridines, namely, 2,3,4,5-tetra-hydropyridine or 1-piperideine (1), 1,2,3,4-tetrahydropyridine or 2-piperideine (2), and 1,2,3,6-tetrahydropyridine or 3-piperideine (3), are all known in the form of derivatives, but only 3-piperideine (3) has been prepared as a stable free base. 

Since there have been many publications in the last few years on the syntheses and reactions of 3-piperideines, it seemed appropriate to compile the present review covering the literature to 1968. 

The chemistry of 3-piperideines has also been the subject of some earlier reviews1 or chapters in monographs.11... 

One of the most frequent routes to 3-piperideines makes use of 4-piperidones (4) as intermediates. The latter compounds are prepared, e.g., by the addition of alkyl 3-acylaminopropionates or 3-alkyl-aminopropionates to alkyl acrylates and subsequent Dieckmann condensation. 

The parent 3-piperideine (3) was prepared from l-acetyl-4-piperi-done by conversion into the p-toluenesulfonylhydrazone and thermal fission of the latter in alkaline media (the Bamford-Stevens reac-... 

In the preparation of l-ethyl-3-piperideine (8), the starting material l-ethyl-4-piperidone (6) was hydrogenated to give 1-ethyl-4-piperi-dinol. Treatment of the latter with thionyl chloride afforded 1-ethyl-4-chloropiperidine, the dehydrohalogenation of which (NaOMe/ MeOH) led to a low yield of l-ethyl-3-piperideine. A somewhat higher yield (37%) was obtained by pyrolysis (500°C) of l-ethyl-4-acetoxypiperidine (7).3... 

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