Synthese und Struktur substituierter N‐Benzyl‐piperidon‐carbonsäureester

Abstract

Zur Freisetzung der Base wurde das Perchlorat in Wasser geliist, mit Natriumearbonat gesgttigt, d t Methylenchlorid ausgeschiittelt, uber Natriumsulfat getrwknet und der Ruckstand der einge dampften Methylenchloridlosung bei 118' und 1,s Torr destilliert. Das Destillat bestand aus reinem 4a. Ausbeute: 6,2 g (32 % d. Th.). = 0'; c = 1,468 (Wasser). In aUen anderen Dateq identisch mit 4. Perchbrat: Schmp. 145-147' (Isopropanol) [C11H17N20]C104 (292,7) IR-Spektrum (KBr): Die Banden unterschieden sich von denen des Perchlorats von 4 durch unterschiedliche Intensitat, besonders im Fingerprint-Bereich. 1 -Methybbamino-S-[ 1 -methyl-pyrrolidyl-(2)]-pyridiniumiodid-hydrojodid (1 2) Aus 8 analog der Darstellung von 11. Schwach gelbe Kristalle, loslich in Methanol, schwer loslich in Aethanol. Schmp. 274-276O (Methanol). Ausbeute: 68 g (76 5% d. Th.) ausgehend von 35,6 g 8.

Stereochemistry of 2,6-Dipyridine Substituted N-Benzyl-4-piperidone Mono- and Dicarboxylates and of the Corresponding Reduction Products

“…3). The structure is differ ent from the one proposed by Haller et al [7,8 ]: The pyridine substituent at C-2 takes an axial position whereas the pyridine ring at C-6 has an equatorial position which results a trans substitution of the pyridine rings*. The benzyl residue at the nitrogen N-l takes an axial position to prevent a steric compression with the aromatic substituents at C-2 and C-6 .…”

“…The condensation of the m onoester of acetonedicarboxylates, pyridine-2-aldehyde and N-benzylamine yields mainly the piperidone lb , which is characterized by the enol structure of the /3-ketoester skeleton as the IR absorptions at 1655 (C^O ) and 1625 cm " 1 (C = C ) indicate [7,8 ]. H aller et al pos tulated equatorial positions for the pyridine rings at C-2 and C-6 as well as for the carboxylate function at C-3 in analogy to the ketone form of the dimethyl piperidone 3,5-dicarboxylates [12], There is no indi cation of the configuration at C-2 in the 'H NMR spectra of l b because the hydrogen at C-2 does not have a coupling partner on C-3.…”

“…The IR spec trum in CC14 indicates a ketone (1710 cm-1) and an ester carbonyl group (1735 cm-1) [8]. The NMR coupling constant of J = 5.5 Hz between the hydro gens at C-2 and C-3 assigns an axial position of the pyridine ring at C-2.…”

“…The synthesis of the 2,6-di-2-pyridine substituted methyl N-benzyl-4-piperidone-3-carboxylate (lb ) was carried out as reported by H aller et al [7,8 ]. The ketone isomer l a was obtained along with lb from the first crystallisation fraction, only.…”

“…These results have prom pted the present study of the stereochemistry of the 2 ,6 -dipyridine sub stituted N-benzyl-4-piperidone-3-carboxylates and -3,5-dicarboxylates 1 and 2. Usually dimethyl 4-piperidone-3,5-dicarboxylates 2 are synthesized by a Mannich procedure from dimethyl acetonedicarboxylates, an aldehyde and an alkylamine [3 -6 ] and the monoester of the piperidone 1 by a condensation of the monoester of acetonedicarboxylates, aldehyde and alkylamine [7,8 ], respectively. These syntheses characteristically yield a mixture of isomeres, which could be identified as keto-enol-tautom erism as well as configurational isomers at C-2/C-6, especially in the case of the 2,6-diphenyl substituted N-methyl and N-benzyl-4-piperidone-3,5-dicarboxylates [4b, 5 a].…”