Synthesis and stereochemistry of highly crowded N-benzylpiperidones
ABSTRACT A series of N-benzylated 3,5-diakyl-2,6-diarylpiperidin-4-ones 4-8 were conveniently synthesized in significant yields of 68-88% by N-benzylation of the corresponding 2,6-diaryl-3,5-dimethylpiperidin-4-ones 1-3 using different benzyl bromides. Initially, the new piperidone 2,6-bis(4-ethoxyphenyl)-3,5-dimethylpiperidin-4-one 3 was synthesized by the condensation of 1:1:2 M ratio of 3-pentanone, ammonium acetate and para-ethoxybenzaldehyde in ethanolic medium. All the synthesized new compounds 3-8 were characterized by their analytical and spectral (IR, 1H and 13C NMR) interpretations. The stereochemistry of the new piperidone 3 was elucidated as chair conformation with an equatorial orientation of all substituents, suggested by its vicinal couplings from 1H NMR spectrum. To investigate the impact on piperidone stereochemistry as well as NMR chemical shifts, all the N-benzylated products 4-8 were compared with their corresponding precursors, and as a result, it is clearly established that all the synthesized N-benzyl piperidones exist in the chair conformation with an equatorial orientation of all the substituents at C-2, C-3, C-5, C-6 and N. Contrary to the probability all N-benzylated compounds retain the same conformation and configuration as their precursors, however, a remarkable change on the chemical shifts are observed. For the further unambiguous confirmation of stereochemistry, the 1-benzyl-3,5-dimethyl-2,6-diphenylpiperidin-4-one 4 was examined by single-crystal X-ray diffraction. The compound 4, C26H27NO, crystallized in a P-1 space group under triclinic system with unit cell dimensions a, b, c (Å) and α, β, γ (°) of 10.1562(7), 11.0018(7), 11.3476(8) and 116.7440(10), 100.8070(10), 100.1730(10), respectively.
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ABSTRACT: A series of fifteen diversified N-benzylpiperidin-4-one oximes were synthesized and characterized by their NMR spectral data. Additionally, single-crystal XRD analysis was performed for the representative symmetrically and unsymmetrically substituted molecules. All the synthesized oximes from unsymmetrical ketones existed as E-isomer as witnessed by their NMR and XRD data. Among the synthesized target com-pounds that evaluated for their in vitro cytotoxicity against human cervical carcinoma (HeLa) cells, five com-pounds were potent with IC 50 < 17 μM. 1-Benzyl-2,6-bis(4-isopropylphenyl)-3-methylpiperidin-4-one oxime 3c with an IC 50 of 13.88 μM was found to be the best active compound as depicted by the microscopic analysis.Journal of Chemical Sciences 05/2014; 126(3):861-873. DOI:10.1007/s12039-014-0622-z · 1.22 Impact Factor