Chemistry of the phenoxathiins and isosterically related heterocycles. IX.N-oxidation on the 13C-nmr chemical shifts and coupling constants of the 1-azaphenoxathiin system

The synthesis of 1-azaphenoxathiin N-oxide is described. Total assignment of the ¹³C-nmr spectrum and the effects of the N-oxide moiety on the chemical shifts and ¹H-¹³C spin couplings constants are described and compared to the parent 1-azaphenoxathiin system. The potential for the use of N-oxidation induced changes in ¹³C-nmr chemical shifts and ¹H-¹³C coupling constants as an assignment criterion is also discussed.     

Chemistry of the phenoxathiins and isosterically related heterocycles. XXX. The crystal and molecular structure of 2-AZA-phenoxathiin 2-oxide: Further evidence in support of the relationship between the 13C-NMR chemical shift of C-10a resonance and the molecular dihedral angle

The synthesis of 2-azaphenoxathiin 2-oxide ( 4 ) and the total assignment of the ¹³C-nmr spectrum is described. Facile assignment was obtained from the assigned spectrum of 2-azaphenoxathiin with additivities obtained from a comparison of 1-azaphenoxathiin and its N-oxide. The crystal structure has also been determined from three dimensional X-ray diffraction data. The compound crystallizes in the monoclinic space group P2₁/n with a = 17.50(2)Å, b = 7.147(3)Å, c = 16.044(7)Å, β = 110.60(5) and Z = 8. Intensity data were collected at - 135 ± 2°C on an automatic diffractometer using nickel-filtered CuKα radiation. The structure was solved by direct methods and was refined by least-squares techniques to give a final R-value of 0.045 for all 3831 independent reflections.     

Chemistry of the phenoxathiins and isosterically related heterocycles. XXII. 6,7,9-trimethyl-4-azaphenoxathiin: First reported synthesis of an analog of the 4-azaphenoxathiin ring system

The reaction of 2-chloro-3-thiocyanatopyridine with a substituted spiroepoxycyclohexadienone, which served as a masked phenol with reversed polarity, led to the first reported synthesis of an analog of the 4-azaphenoxathiin ring system. Confirmation of the structure was obtained from the assignment of the ¹³C-nmr spectrum.     

Chemistry of the phenoxathiins II. Synthesis of 1-azaphenoxathiin

The synthesis of 1-azaphenoxathiin, the parent ring system of a recently reported class of novel CNS agents is described. The ¹³C-nmr spectrum and its assignment are also reported as a model for structure confirmation studies.     

Chemistry of the phenoxathiins and isosterically related heterocycles. XIII. 13C-NMR spectroscopy of 1-azaphenoxathiin 10,10-dioxide. An unusual perturbation of 1H-13C coupling constants

The total assignment of the ¹³C-nmr spectrum of 1-azaphenoxathiin 10,10-dioxide is reported based on the utilization of additivity correlations for the conversion of sulfide to sulfone linkages. Although the benzenoid portion of the molecule obeyed standard additivity correlations, substantial deviation in additivity behavior was observed in the pyridyl portion of the molecule. Examination of the ¹H-¹³C spin-coupling constants showed a perturbation of the primary one bond (¹J_CH) couplings of the C-2 and C-4 carbons.     

Chemistry of the phenoxathiins and isosterically related heterocycles. XVI. The synthesis and molecular structure of 3-azaphenoxathiin: Evidence in support of factors responsible for control of the dihedral angle

The synthesis of the 3-azaphenoxathiin ring system and its molecular structure are reported. Based on ¹³C-nmr chemical shift additivities associated with the insertion of an annular nitrogen atom and the observed ¹³C-nmr shift of Cα, the title compound was predicted to have a dihedral angle θ = 160.2°. The observed dihedral angle from the crystal structure was found to be θ = 167.07° which is in reasonably good agreement with the predicted value. It is proposed that the position of the annular nitrogen atom is solely in-control of the observed dihedral angle.     

Chemistry of the phenoxathiins and isosterically related heterocycles. XXIII . 1-azathianthrene: First reported synthesis of a monoazathianthrene and the investigation of the 13C-NMR spectrum using two-dimensional NMR techniques

The reaction of the dianion of 3-mercaptopyridin-2(1H)-thione with 2-chloronitrobenzene in N,N-dimethylformamide leads to the formation of 1-azathianthrene, the first reported mono-aza analog of the thianthrene ring system. A partial assignment of the ¹³C-nmr spectrum of the title compound is reported, the assignment based on chemical shift arguments, spin-lattice (T₁) relaxation times and ¹H-¹³C spin coupling constants. Amplitude modulated two-dimensional Fourier transform (AM2DFT) techniques were employed for the acquisition of the heteronuclear spin-coupling constants.     

Two-Dimensional NMR Studies of Polyene Systems. I. All-trans-Retinal

Two-dimensional (2-D) NMR results are presented for all-trans-retinal. 2-D J-resolved ¹H-NMR separated the multiplets of the olefinic protons and accurately determined their chemical shifts. 2-D shift-correlated ¹H-NMR gave the connectivities between scalar coupled protons. From the observed H,H long-range couplings the assignment of the methyl resonances was possible. 2-D J-resolved ¹³C-NMR separated overlapping C,H-multiplets and allowed analysis of the C,H long-range couplings, 2-D shift-correlated ¹³C-NMR related each directly bonded C,H-pair in this molecule. The potential of 2-D NMR in resolving and identifying individual resonances in polyene spectra is discussed.     

Empirical additive parameter and automatic assignment of 13C NMR signals of some aryl and heteroaryl groups. A new criterion for a linear relationship between 13C chemical shifts and charge densities

The ¹³C NMR signals of some mono- and disubstituted aryl compounds were assigned by means of empirical additive substituent parameters and information taken from fully coupled spectra. This assignment was compared with that obtained with the help of the method of automatic assignment of the signals based on the linear relationship between ¹³C chemical shift and charge density. The results show that in the cases of XR substituents (X = O, NH and R = H, CH₃, CH₂CH₂OH) a good correlation is observed and the automatic assignment is correct. In contrast, in the cases of ? CH₂CH₂Y substituents (Y = OH, NH₂, Cl) a worsening of the correlation is observed and the automatic assignment is not correct. It is suggested that for compounds with a preliminarily known assignment, the automatic assignment can serve as an additional criterion for the reliability of the linear relationship between ¹³C chemical shift and charge density.     

Chemistry of the phenoxathiins and isosterically related heterocycles. XVIII. The synthesis, 1H- and 13C-NMR Spectroscopy of benzo[b]-1,4,9-triazaphenoxathiin

The first synthesis of a triazaphenoxathiin system, benzo[b]-1,4,9-triazaphenoxathiin, is reported. Attempts directed toward the total assignment of the ¹³C-nmr spectrum of the title compound failed to produce an unequivocal assignment. The carbons of the benzo-portion of the molecule could not be unequivocally assigned at 25.2 MHz but were subgrouped into permutable pairs of resonances on the basis of relaxation times, a result of the antisotropic reorientation of the molecule. Further attempts to complete the ¹³C-nmr assignment at 100 MHz by selective on-resonance decouplings in the 400 MHz ¹H-nmr spectrum were also unsuccessful because of similarities in the chemical shifts of the benzo-protons. Complete ¹H-nmr chemical shifts and homo-nuclear spin-coupling constants were obtained using the PANIC program.     

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

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 ¹⁷O chemical shift of the N⁺―O^– oxygen in the N‐oxides and the ¹³C 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 ¹⁷O chemical shift of only one N‐epimer is available, provided the ¹³C chemical shifts of both N⁺―CH₃ groups in the methiodide are known and assigned; furthermore, it can be used also for the estimation of ¹⁷O chemical shifts of the N⁺―O^– oxygens in N‐epimeric pairs of N‐oxides, for which observed ¹⁷O data hardly become available. The second correlation is observed between the ¹³C chemical shift of the N⁺―CH₃ methyl group in the N‐oxides and the ¹³C 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 ¹⁷O NMR data, and the ¹³C chemical shift of only one N‐epimer is available. Copyright © 2015 John Wiley & Sons, Ltd.     

Carbon-13 NMR studies of substituted naphthalenes. II—rotational barriers and conformations in some naphthaldehydes and azulenaldehydes

Proton-coupled and noise-decoupled ¹³C NMR spectra of 1-azulenecarbaldehyde, 1-acetylazulene and 1,3-azulenedicarbaldehyde have been studied, and complete assignments have been made based on the ¹³C? ¹H coupling constants, additivity of substituent effects (SIS), and previous assignment for the parent hydrocarbon. The barriers to rotation of the aldehyde group in the above azulenecarbaldehydes and in some naphthaldehydes have been determined by ¹³C dynamic NMR, (DNMR), resulting in free energies of activation of 42.7, 26.8 and 34.4 kJ mol^?1 for 1-azulenecarbaldehyde, 1-naphthaldehyde and 2-naphthaldehyde respectively. The same order of barriers is obtained by CNDO/2 calculations. A 4-methoxy substituent in 1-naphthaldehyde and a 6-methoxy substituent in 2-naphthaldehyde increases the rotational barrier by 4.6 and 2.9 kJ mol^?1, respectively, whereas a 3-methoxy substituent in 2-naphthaldehyde reduces the barrier by 6.7 kJ mol^?1. The conformations of the dominant rotamers are deduced from ¹³C chemical shifts to be Z for 1-azulenecarbaldehyde and 1-naphthaldehyde, and E for 2-naphthaldehyde.     

Long range optimized two-dimensional proton-carbon chemical shift correlation. Application in the total assignment of the 1H- and 13C-NMR spectra of 9-methylphenanthro[4,3-a]dibenzothiophene

The utilization of the long range optimized proton-carbon chemical shift correlation experiment in the total assignment of the proton and carbon nmr spectra of 9-methylphenanthro[4,3-a]dibenzothiophene is described. The experiment was employed in concert with conventional proton-carbon chemical shift correlation, heteronuclear relayed coherence transfer and broad band homonuclearly decoupled proton-carbon chemical shift correlation experiments. The experiments in combination offer a useful alternative to the ¹³C-¹³C double quantum coherence experiments, providing significantly better sensitivity and nearly the same capabilities.     

Linear and angular annelation effects on the 13C NMR spectra of tricyclic aromatic ketones. 1—annelated indanones

Carbon-13 NMR chemical shifts are reported for nine tricyclic aromatic ketones formally derived from indanone. The influences of remote ring size, as well as linear, angular exo and angular endo ketone orientation are examined. Results are compared with available ¹H NMR data. For indanone itself, based on selective ¹H decoupling experiments, a recently reported CIDNP derived ¹³C signal assignment is shown to be in error.     

4,5-Dibenzyloxybenzyne as a synthon for diels-alder reactions. The synthesis of 6,7-dihydroxy-1,4-ethano-1,2,3,4-tetrahydroisoquinolines as rigid analogs of adrenergic agents. Assignment of proton and carbon-13 NMR parameters using homonuclear and heteronuclear two-dimensional chemical shift correlation NMR spectroscopy

The synthesis of several rigid analogs of catecholamine type of adrenergic agents is reported. Their synthesis began with a Diels-Alder cycloaddition of 4,5-dibenzyloxybenzyne (generated from 4,5-dibenzyloxyan-thranilic acid) to 1-(2-trans-phenylvinyl)-2-pyridone and 1-benzyl-3-benzyloxy-2-pyridone. The unsaturated amides so produced were reduced first with hydrogen and palladium and then with lithium aluminum hydride to provide 6,7-dihydroxy-1,4-ethano-1,2,3,4-tetrahydroisoquinolines. Homonuclear and heteronuclear two-dimensional chemical shift correlation nmr spectroscopy confirmed the structure of the bridged tetra-hydroisoquinolines and led to the unambiguous assignment of the ¹H and ¹³C nmr chemical shifts of key compounds.     

The study of longifolene by two-dimensional NMR spectroscopy

The complete assignment of the ¹³C NMR spectrum of longifolene was achieved from double quantum coherence measurements, while combined evaluation of a ¹H? ¹³C heteronuclear chemical shift correlation diagram and a homonuclear ¹H J-resolved diagram provided all proton chemical shifts. Conformational information on the seven-membered ring of the tricyclic sesquiterpene was obtained from proton chemical shift considerations.     

Assignment of the 1H- and 13C-NMR spectra of phenanthro[1,2-b]thiophene through the concerted application of two-dimensional NMR spectroscopic techniques

Two-dimensional nmr spectroscopy, by virtue of its second frequency domain which permits the segregation of spectral information along two frequency axes, considerably simplifies many assignment problems and facilitates others which may be impossible using conventional nmr methodology. A compound which falls into the latter category of assignment problem is phenanthro[1,2-b]thiophene. The assignment of the ¹H- and ¹³C-nmr spectra of phenanthro[1,2-b]thiophene are, however, reported through the concerted application of two-dimensional nmr techniques. Experiments utilized in making the assignments included: auto-correlated homonuclear (COSY) two-dimensional spectroscopy; heteronuclear two-dimensional J-resolved spectroscopy; proton-carbon chemical shift correlation two-dimensional spectroscopy; and two-dimensional ¹³C-¹³C double quantum coherence spectroscopy.     

The synthesis of novel polycyclic heterocyclic ring systems. 2. Naphmo[2,1-b:4,3-g]bisbenzo[b]thiophene

The novel polycyclic heterocyclic ring system, naphtho[2,1-b:4,3-g]bisbenzo[b]thiophene was synthesized from 5-[2-(2-bromo-3-thienyl)ethenyl]naphtho[2,1-b][1]benzothiophene. The assignment of its ¹H and ¹³C nmr spectra was also accomplished by utilizing two-dimensional nmr methods.     

The assignment of the 1H and the 13C NMR chemical shifts of N-phenyl-2,4-dimethylbuta-1,3-diene-1,4-sultam

The assignment of the signals in the ¹³C and ¹H NMR spectra of N-phenyl-2,4-dimethylbuta-1,3-diene-1,4-sultam is difficult for the signal pairs C-2 and C-4, C-1 and C-3, (C-1)? H, (C-2)? CH₃ and (C-4)? CH₃. The ¹³C NMR spectrum recorded under gated decoupling conditions provide long-range couplings which make possible an unambiguous assignment of the ¹³C NMR signal pairs. Application of the ¹H CW off-resonance decoupling technique in recording the ¹³C NMR spectra enables the assignment information from the ¹³C NMR spectrum to be transferred to the ¹H NMR spectrum.