RESUMEN
The paper presents the experimental and DFT-calculated values of the 13 C NMR chemical shifts of the six stereoisomers of tetradecahydroacridine and of the corresponding nitrosamines. Performing the DFT calculations using several combinations of functional and basis sets, it was found that the best experimental-calculated agreement was obtained for OPBE/6-311++G (dp) method. Considering the effect of N-nitrosation upon the 13 C NMR chemical shifts of the C-α carbons of secondary amines, it was found that if following nitrosation both C-α carbons are shifted upfield or both are shifted downfield, then the resulted nitrosamine will have a sterically strained âNâO group. If, however, one of the C-α is shifted upfield and the other is shifted downfield, then the âNâO group will be strain-free or weakly strained. Our calculations predict strain energies of about 10-15 kcal mol-1 in the first case and ≈0-6 kcal mol-1 in the latter.
RESUMEN
Two kinds of good linear correlations were found between the chemical shifts of saturated six-membered azaheterocyclic N-methylamine N-oxides and the chemical shifts of the methiodides of their parent amines. One of the correlations occurs between the (17)O chemical shift of the N(+)-O(-) oxygen in the N-oxides and the (13)C chemical shift of the N(+)-CH3 methyl group analogously situated in the appropriate methiodide (r = 0.9778). This correlation enables unambiguous configuration assignment of the N(+)-O(-) bond, even if the experimentally observed (17)O chemical shift of only one N-epimer is available, provided the (13)C chemical shifts of both N(+)-CH3 groups in the methiodide are known and assigned; furthermore, it can be used also for the estimation of (17)O chemical shifts of the N(+)-O(-) oxygens in N-epimeric pairs of N-oxides, for which observed (17)O data hardly become available. The second correlation is observed between the (13)C chemical shift of the N(+)-CH3 methyl group in the N-oxides and the (13)C chemical shift of the N(+)-CH3 methyl group analogously situated in the appropriate methiodide (r = 0.9785). It can be used for safe configuration assignment of the N(+)-CH3 group and, indirectly, also of the N(+)-O(-) bond in an amine N-oxide, even if no (17)O NMR data, and the (13)C chemical shift of only one N-epimer is available.
RESUMEN
Tropane, tropinone, pseudopelletierine and cocaine were oxidized in situ in a nuclear magnetic resonance (NMR) tube providing mixtures of exo/endo N-oxides. Observed (13)C chemical shifts were correlated with values calculated by gauge-including atomic orbitals density functional theory (DFT) OPBE/6-31G* method using DFT B3LYP/6-31G* optimized geometries. The same method of (13)C chemical shift calculation was applied on series of methyl-substituted 1-methylpiperidines and their epimeric N-oxides described in literature. The results show that using this undemanding calculation method enables assignment of configuration of N-O group in N-epimeric saturated heterocyclic N-oxides. The approach enables assigning of the configuration with high degree of certainty even if NMR data of only one isomer are available. An improved method of in situ oxidation of starting amines in an NMR tube is also described.
Asunto(s)
Óxidos N-Cíclicos/química , Modelos Químicos , Nitrógeno/química , Resonancia Magnética Nuclear Biomolecular/métodos , Oxígeno/química , Isótopos de Carbono , Cocaína/química , Conformación Molecular , Oxidación-Reducción , Piperidinas/química , Valor Predictivo de las Pruebas , Estereoisomerismo , Tropanos/químicaRESUMEN
The interaction of 3-carboxy-5,6-benzocoumarin (BzCum) with 1,2,3,4,5,6,7,8-octahydroacridine (OHA), 9-amino-1,2,3,4,5,6,7,8-octahydroacridine (H(2)N-OHA) and the corresponding N-oxides (OHA-NO and H(2)N-OHA-NO) was studied by fluorescence (steady state, time resolved) and absorption spectroscopy. The analysis of the fluorescence data in terms of Stern-Volmer plots indicated a predominant dynamic quenching for OHA and OHA-NO, and a more complex process for H(2)N-OHA and H(2)N-OHA-NO. The dynamic process was assigned to a photoinduced electron transfer (PET) from the acridine derivatives to the excited state of BzCum. The application of the Rehm-Weller-Marcus theory leads to a good agreement with literature data and allows for the estimation of the solvent organization energy. The presence of the PET mechanism was also supported by DFT results. The absorption spectra evidence the formation of a ground state complex assigned to a hydrogen bond complex involving the carboxylic hydrogen of BzCum.
Asunto(s)
Acridinas/química , Acridinas/farmacología , Cumarinas/química , Cumarinas/farmacología , Óxidos N-Cíclicos/química , Óxidos N-Cíclicos/farmacología , Absorción , Química Analítica , Interacciones Farmacológicas , Enlace de Hidrógeno , Modelos Biológicos , Modelos Moleculares , Modelos Teóricos , Estructura Molecular , Análisis Espectral/métodosRESUMEN
The 1H and 13C NMR chemical shifts of 1,2,3,4,5,6,7,8-octahydroacridine, 12 of its 9-substituted derivatives, and of the corresponding N-oxides were determined, assigned, and discussed in terms of 9-substituent effects and effects of N-oxidation. A good linear correlation was found between the 13C chemical shifts of the aromatic carbons in octahydroacridines and those of respective carbons in the corresponding N-oxides.
Asunto(s)
Acridinas/química , Óxidos/química , Isótopos de Carbono , Espectroscopía de Resonancia Magnética , Estructura Molecular , Protones , Estándares de Referencia , EstereoisomerismoRESUMEN
The (15)N NMR chemical shifts of 1,2,3,4,5,6,7,8-octahydroacridine, 12 of its 9-substituted derivatives, and of the corresponding N-oxides were measured and examined in terms of the 9-substituent effects and the effects of N-oxidation. For the 9-substituent effects, good linear correlations were found with the Taft and Swain-Lupton substituent constants, for both octahydroacridines and their N-oxides. The (15)N chemical shifts of both octahydroacridines and their N-oxides also correlate well, linearly with the (13)C chemical shifts of the para-carbons in analogously substituted benzene derivatives.Within the studied compounds, the magnitudes of the N-oxidation effects range from - 16.4 to - 27.4 ppm (shielding), and also correlate linearly with the Taft and Swain-Lupton substituent constants, as well as with the bond orders of the N(+)-O(-) bonds in the corresponding N-oxides. Furthermore, a very good linear correlation is found between the (15)N chemical shifts of octahydroacridines and those of the corresponding N-oxides. From the (15)N chemical shifts data, the Taft and Swain-Lupton substituent constants for the diacetylamino group (-NAc(2)) were evaluated in the present paper, as follows: sigma(R) = 0.07 and sigma(I) = 0.15; R = 0.08 and F= 0.20.
Asunto(s)
Acridinas/química , Espectroscopía de Resonancia Magnética/métodos , Isótopos de Carbono , Isótopos de Nitrógeno , Óxidos/químicaRESUMEN
The (15)N chemical shifts of 13 N-methylpiperidine-derived mono-, bi- and tricycloaliphatic tertiary amines, their methiodides and their N-epimeric pairs of N-oxides were measured, and the contributions of specific structural parameters to the chemical shifts were determined by multilinear regression analysis. Within the examined compounds, the effects of N-oxidation upon the (15)N chemical shifts of the amines vary from +56 ppm to +90 ppm (deshielding), of which approx. +67.7 ppm is due to the inductive effect of the incoming N(+)--O(-) oxygen atom, whereas the rest is due to the additive shift effects of the various C-alkyl substituents of the piperidine ring. The effects of quaternization vary from -3.1 ppm to +29.3 ppm, of which approx. +8.9 ppm is due to the inductive effect of the incoming N(+)--CH(3) methyl group, and the rest is due to the additive shift effects of the various C-alkyl substituents of the piperidine ring. The shift effects of the C-alkyl substituents in the amines, the N-oxides and the methiodides are discussed.