Structure, Conformation, and Stereodynamics of N-Nitroso-2,4-diaryl-3-azabicyclo[3.3.1]nonanes and N-Nitroso-2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-ones(1)

The variable temperature (1)H, (13)C, and (19)F NMR spectra were measured for the title N-nitrosamines. The observed unusually low N-N rotation barriers (12-15 kcal/mol) result from a significant deviation of the nitrosamino system from planarity. A pyramidal character of the amino nitrogen was confirmed by the X-ray crystal structures of two compounds and by bathochromic shifts of the n-pi absorption bands in the UV spectra. The nonplanarity of the nitrosamino moiety is due to the strong pseudoallylic A((1,3)) strain caused by the steric interaction of the NNO group with the neighboring aryl substituents fixed in the equatorial positions of the bicyclic skeleton. In addition, the barriers to the C-C rotation of aryl groups were examined at temperatures lower than required to "freeze" the N-N rotation and different DeltaG() values were observed for the aryls oriented syn and anti to the nitroso oxygen.     

Synthesis and Properties of 3-Thia-9-azabicyclo[3.3.1]nonan-7-one

N-Benzyl-3-thia-9-aza-bicyclo[3.3.1]nonan-7-one has been prepared from methyl 4-bromocrotonate by reaction sequence involving sodium sulfide, benzylamine, and Dieckmann condensation. Some spectral and chemical properties of this system are also reported.     

Synthesis of N-arylmethyl-3-azabicyclo[3.3.1]nonan-9-ones

Russian Journal of Organic Chemistry -     

New homoleptic metal complexes of Schiff bases derived from 2,4-di-p-tolyl-3-azabicyclo[3.3.1]nonan-9-one

New bidentate Schiff-base ligands 2-(2,4-di-p-tolyl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazinecarbothioamide HL¹ and 2-(2,4-di-p-tolyl-3-azabicyclo[3.3.1]nonan-9-ylidene)hydrazinecarboxamide HL² were synthesized from the condensation of 2,4-di-p-tolyl-3-azabicyclo[3.3.1]nonan-9-one with thiosemicarbazide and semicarbazide, respectively. Homoleptic complexes of these ligands, of general formula K[Cr(L ⁿ )₂Cl₂], K₂[Mn(L ⁿ )₂Cl₂], K₂[Fe(L¹)₂Cl₂] and [M(L ⁿ )₂] (where M = Co(II), Ni(II) Cu(II), Zn(II), Cd(II), and Hg(II) ions; n = 1 or 2) are reported. The mode of bonding and overall geometry of the complexes were determined through IR, UV-Vis, NMR and mass spectral studies, magnetic moment measurements, elemental analysis, metal content, and conductance. These studies revealed octahedral geometry for Cr(III), Mn(II), and Fe(II) complexes, square planar for Cu(II), Co(II), and Ni(II) complexes and tetrahedral for Zn(II), Cd(II), and Hg(II) complexes.     

Schmidt reaction and beckmann rearrangement in the series of 3-azabicyclo[3.3.1]nonan-9-one derivatives

Russian Journal of Organic Chemistry -     

Assymetric syntheses of the ladybug alkaloid adaline and 1-methyl-9-azabicyclo [3.3.1]nonan-3-one

The double Michael addition of benzylamine to 3-alkyl-2,7-cyclooctadienones, followed by hydrogenolysis, affords bridgehead substituted 9-azabicyclo[3.3.1]nonan-3-ones. Use of (+)-α-methylbenzylamine in the addition leads to mixtures of diastereomeric adducts in unequal amounts. Although the degree of asymmetric induction is low (10–20% ee), the diastereonomers can be easily separated, affording pure enantiomeric forms of the ladybug alkaloid adaline 1 and the Euphorbia alkaloid 3.     

Reactions of 3-substituted 3-azabicyclo[3.3.1]nonan-9-ones with nitrogen-containing nucleophiles

Condensation of 3-substituted 3-azabicyclo[3.3.1]nonan-9-ones with hydroxylamine and hydrazine hydrate gave the corresponding oximes, hydrazones, and azines. Reductive amination of the title compounds in the presence of sodium triacetoxyhydridoborate led to the formation of 3-substituted 3-azabicyclo[3.3.1]nonan-9-amines which were converted into the corresponding dihydrochlorides by treatment with dry hydrogen chloride. Treatment of 3-tert-butoxycarbonyl derivatives with HCl under analogous conditions was accompanied by elimination of the tert-butoxycarbonyl group to produce 3-azabicyclo[3.3.1]nonan-9-amine dihydrochlorides.     

Structural study of 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9β-ol

The infrared spectra in several media and the crystal structure of 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]-nonan-9β-ol ( I ) (Scheme I) have been determined, in order to complete the structural study described for the title compound from the ¹H and ¹³C nmr data [1]. The bicyclic system adopts a flattened chair-chair conformation in which the cyclohexane ring is more flattened. The methyl and phenyl groups are in equatorial positions and the OH group in an axial position with respect to the piperidine ring.     

Chemistry of 3-Azabicyclo[3.3.1]nonane: II. Reduction of 6-Acetoxy-3-benzyl-1- ethoxycarbonyl-3-azabicyclo[3.3.1]nonan-9-one with Sodium Borohydride

Reduction of 6-acetoxy-3-benzyl-l-ethoxycarbonyl-3-azabicyclo[3.3.1]nonan-9-one with sodium borohydride was investigated in various conditions. The stereochemistry of reduction products was deduced from ¹H and ¹³C NMR and mass spectra.     

Synthesis, complete NMR spectral assignments, and antifungal screening of new 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one oxime derivatives

Abstract  

A series of differently substituted 2,4-diaryl-3-azabicyclo[3.3.1]nonan-9-one oximes have been synthesized and their ¹H and ¹³C NMR chemical shifts have been unambiguously assigned using H,H-COSY, NOESY, HSQC, and HMBC spectral data. On the basis of the NMR studies, irrespective of the nature and position of the substituents, all reported compounds exist in twin-chair conformation with equatorial disposition of the phenyl groups at C-2 and C-4 of the 3-azabicyclononane moiety. Among the synthesized oxime derivatives, compounds with halo-substituents at ortho/para positions of the phenyl showed good antifungal profile against all tested organisms.     

Synthesis of 1-azabicyclo[3.2.2]nonan-4-one

The synthesis of 1-azabicyclo[3.2.2]nonan-4-one has been effected by the reaction of quinuclidin-3-one with diazomethane.Translated from Khimiya Geterotsiklicheskikh Soedinenii, Vol. 6, No. 8, pp. 1037–1040, August, 1970.     

内-9-甲基-9-氮杂二环[3.3.1]壬-3-烷胺的合成工艺改进

以柠檬酸为起始原料,经氧化、Mannich反应、成肟、LiAlH4还原以及内外式产物分离,合成了制备盐酸格拉司琼的关键中间体内-9-甲基-9-氮杂二环[3.3.1]壬-3-烷胺,总收率16.8%.其结构经1H NMR,IR和MS表征.     

Structure elucidation with lanthanide induced shifts. 9. bicyclo[3.3.1]nonan-9-one

Lanthanide shift reagents have been used for the conformational analysis of bicyclo[3.3.1]-nonan-9-one. Comparison of predicted shifts and experimental values obtained with Eu(fod)₃ indicate that the boat-chair conformation constitutes 22% of the mixture of conformers.     

Crystal and molecular structure of 6,6-dimethyl-cis-2,4-diphenyl-3-aza-7-oxabicyclo[3.3.1]nonan-9-one

A method is presented for synthesizing 6,6-dimethyl-2,4-diphenyl-3-aza-7-oxabicyclo[3.3.1]nonan-9-one. The x-ray structure shows that the compound in the crystal exists in the chair-boat conformation with the piperidine ring in the boat form. The two phenyl substituents in the 2- and 4-positions are responsible for such a conformation.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 10, pp. 1400–1402, October, 1990.     

Exploring potential energy hypersurfaces for triple symmetric inversion in 3-azabicyclo[3.3.1]nonan-9-one and its N-methyl derivative

The potential energy hypersurfaces for the triple inversion, from chair to boat and α to β conformations, are explored theoretically in 3-azabicyclo[3.3.1]nonan-9-one and its N-methyl derivative, by using ab initio quantum-mechanical calculations. Both compounds are precursors of rigid analogs of the potential GABA_A and GABA_B receptor antagonists. In contrast to results from semiempirical calculations, the chair–chair β conformers are found to be, by far, the most stable structures for both the nonmethylated and N-methylated compounds. The inversion barriers are found to be relatively low, so that the conformers could be expected to exist in thermodynamic equilibrium at room temperature. A population analysis reveals, however, that, in the ab initio approach, the molecules seem to exist practically only in the chair–chair–β conformation. The theoretical results compare well with the available experimental data. © 1998 John Wiley & Sons, Inc. J Comput Chem 19: 1567–1574, 1998     

Spectroscopic study of 3-methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-α(β)-ols

3-Methyl-2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-α(β)-ols have been synthesized and studied by ir, ¹H and ¹³C nmr spectroscopy. In deuteriochloroform and perdeuteriobenzene solutions, these compounds adopt a flattened chair-chair conformation in which the cyclohexane ring is more flattened. From the ¹H and ¹³C nmr data, several stereoelectronic effects have been deduced. The complete and unambiguous assignment of all protons of the 3-azabicyclo[3.3.1]nonane system, not described up to date, has been carried out.