A new molecule, 3,5-dimethyl-2,6-bis(2,4-dichlorophenyl) piperidin-4-one was synthesized by a modified Mannich condensation of 2 moles of 2,4-dichlorobenzaldehyde, 1mole each of 3-pentanone and ammonium acetate (instead of amine in the typical procedure) in ethanol; recrystallized with ethanol to afford the pale yellow powder with 56% yield. The molecule was characterized by IR, 1H NMR,13C NMR and elemental analysis. Based on the NMR data, it is identified that the molecule exists in a chair conformation with equatorial orientation of all the substituents. Apart, few interesting NMR results are, (i) a broad singlet was observed for the active methine protons at C-3 and C-5, instead of a multiplet, (ii) significant deshielding of the protons at C-2 and C-6 due to the interaction of these protons with chlorine atoms at ortho positions (2’a and 6’a) of the phenyl groups; leads to restricted rotation of the phenyl groups as well, (iii) The ortho protons of 2,4-dichloro phenyl (2’e and 6’e) were also deshielded by nitrogen lone pair; about half of the deshielding magnitude is due to the protons at C-2 and C-6. Antioxidant efficacy of the molecule was verified with DPPH and ABTS methods.
Synthesis of new molecules with bio-potent piperidine/piperidone skeleton and their stereochemical investigation are important in the field of medicinal chemistry due to the presence of piperidine/piperidone skeleton as a building block in numerous naturally occurring alkaloids and biologically active compounds. Since the stereochemistry of any molecules plays vital role in eliciting their biological response, it is very important to ascertain the configuration and conformation of the molecules that obtained for the biological screening. Hence, it was planned to synthesis some polyfunctionalized piperidin-4-ones as new bio-active molecules to establish their stereochemistry. Particularly, the synthesis has been targeted to polyfunctionalized 2,6-bis(polymethoxyphenyl)piperidin-4-ones in view of the fact that the methoxy groups are responsible for various biological actions including antioxidant property. Thus, the target molecules 3,5-dimethyl-2,6-bis(3,4-dimethoxyphenyl)piperidin-4-one (1) and 3,5-dimethyl-2,6-bis (2,5-dimethoxyphenyl)piperidin-4-one (2) were achieved as single isomer by modified Mannich condensations. Identification and characterization of the synthesized molecules were made by analytical (TLC, melting point, elemental analyses) and spectral (IR and NMR) studies. The NMR spectral studies, particularly, the proton NMR spectral data were very useful to determine the configuration and conformation of the new molecules 1 and 2. Accordingly, both of them exist in chair conformation with equatorial orientations of methyl groups on the active methylene centers (C-3 and C-5) and polymethoxyphenyl groups on both sides of the secondary amine (C-2 and C-6). Another interesting observation from the proton NMR is, the ortho substitution on 1 (i.e., molecule 2) cause a significant deshielding on benzylic (H-2a/H-6a) and ortho protons, and a minor deshielding on methinic protons (H-3a/H-5a), whereas, all the above three signals appear as broad singlet due to the restricted rotation by the interaction of ortho methoxy groups with the methyl groups at C-3 and C-5. KEY WORDS:Mannich reaction, Mannich base, Polymethoxyphenyl, Piperidin-4-one, Ortho effect. INTRODUCTIONNitrogen heterocycles represent a vital role in organic chemistry especially in the field of medicinal chemistry (Angle, 1995). Nitrogen heterocycle is present as part of the skeletal backbone of many therapeutic agents and naturally occurring compounds and thus exhibit interesting chemical reactions and important biological actions such as antibacterial, antifungal, antiinflammatory, antiarrhythmic, antiallergic, antiprotozoan, anticholinergic, antitumor, antituberclostic, anticonvulsant, antiviral, antimalarial, local anesthetic, antineoplastic, hypotensive, cytotoxic, muscle relaxant, analgesic, herbicidal, tyrosinase inhibitor, tranquilizer, nicotinic acetylcholine receptor, central nerves system (CNS) stimulant and CNS depressant (Baliah, 1983; Reddy, 1997; Kumar, 2009).It is important to a chemist to understand the broad consequence ...
2,4-Diphenyl-3-azabicyclo[3.3.1]nonan-9-one O-benzyloxime (ABN-OBn) was synthesized by modified Mannich condensation, purified by recrystallization and single crystals were grown by slow evaporation from ethanol. The empirical formula of the molecule is C27H28N2O as witnessed by HRMS, elemental analysis and the X-ray diffraction. The crystal belongs to triclinic system (α = 73.640, β = 78.505, γ = 87.078) with P-1 space group. The electronic excited states of ABN-OBn have been calculated using TD-DFT/B3LYP/6-31G(d,p) level of theory, in order to investigate the electronic transitions within the molecule. Frontier molecular orbitals (FMOs) of ABN-OBn have been studied to understand the electronic charge distributions and its band gap (5.0514 eV/245.45 nm). Density of states (DOS), partial density of states (PDOS) and total density of states (TDOS) with respect to functional groups were computed to investigate the electron densities of functional groups in the molecule. Natural bond orbital (NBO) has been performed to explore the intramolecular π-π* interaction of the compound.
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