¹³C GIAO DFT calculation as a tool for configuration prediction of N–O group in saturated heterocyclic N‐oxides

Abstract

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.

Aerobic Oxidation of 4-Alkyl-N,N-dimethylbenzylamines Catalyzed by N-Hydroxyphthalimide: Protonation-Driven Control over Regioselectivity

“…After distillation, pure N -methyl-4-methylpiperidine was obtained as a colorless oil (2.1 g, 18.7 mmol, 23%): 1 H NMR (CDCl 3 , 300 MHz) δ 2.80 (d, J = 11.8 Hz, 2H), 2.25 (s, 3H), 1.90 (t, J = 11.4 Hz, 2H), 1.61 (d, J = 10.7 Hz, 2H), 1.29–1.21 (m, 3H), 0.91 (d, J = 5.9 Hz, 3H); 13 C NMR (CDCl3, 75 MHz) δ 21.8, 30.1, 34.3, 46.4, 55.9; EI-MS (70 eV) m / z (relative intensity) 113 (M + , 38), 112 (100), 98 (7), 70 (20), 58 (7). 13 C NMR spectrum was in agreement with that reported in the literature …”

“…13 C NMR spectrum was in agreement with that reported in the literature. 30 Product Characterization. 4-Ethylbenzaldehyde, 4-isopropylbenzaldehyde, and 4-benzylbenzaldehyde obtained in the NHPI-promoted oxidation of 1−3 in MeCN were characterized by comparison with commercial samples.…”

Was passiert bei der Reifung von Birne und Kiwi? – Ein Experiment zur Titration mit Bezug zur Natur

“…Unsere quantenchemischen Modell‐Rechnungen für die Gasphase ergeben in Übereinstimmung mit früheren experimentellen und theoretischen [20, 21] Untersuchungen in Lösung eine geringe energetische Bevorzugung (1,7 kJ/mol; mp2/Def2TZV) der Konformation CC2 mit axialer N‐CH 3 ‐Gruppe im Piperidon‐Ring. Dies wird mit geringerer sterischer Hinderung eines axialen Substituenten im abgeflachten Piperidon‐Ring erklärt.…”

Saturated amine oxides: part 10. hydroacridines: part 32. linear 17O/13C and 13C/13C chemical shift correlations between saturated azaheterocyclic N‐methylamine N‐oxides, and the methiodides of their parent amines

“…In our interest concerning the stereochemistry of saturated, N ‐methylpiperidine‐derived monocyclic, dicyclic, and polycyclic amine N ‐oxides, we now have investigated and found a good linear correlation between the 17 O chemical shifts of the oxygen atoms in the N + ―O – groups of N ‐oxides and the 13 C chemical shifts of the carbon atoms in the analogously situated N + ―CH 3 groups in the methiodides of their parent amines, according to Eqn . This correlation can be used as an independent method or in conjunction with other NMR‐based and/or computation‐based methods, for the configuration assignment of N + ―O – groups within members of N ‐epimeric pairs of saturated N ‐methylpiperidine‐derived N ‐oxides, provided the 17 O chemical shift of at least one epimer is known, and the 13 C chemical shifts of both N + ―CH 3 groups in the appropriate methiodides are known and assigned. Further, it can be useful also for the estimation of 17 O chemical shifts of the N + ―O – oxygen in saturated N ‐epimeric azaheterocyclic N ‐methylamine N ‐oxides, if the 13 C chemical shifts of both N + ―CH 3 groups in the methiodides of their parent amines are known and assigned.…”