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. XV. Synthesis of 1-nitrophenoxathiin and the relation of the 13C-Nmr chemical shift of the alpha-carbon to the dihedral angle

The synthesis of the previously unreported 1-nitrophenoxathiin is described. The ¹³C-nmr spectrum of the title compound is assigned based on chemical shift additivities and ¹H-¹³C spin-coupling constants. From the observed ¹³C-nmr chemical shift of the alpha-carbon the title compound was predicted to have a molecular dihedral angle, Ø = 143.3°, based on a recently described interrelation between the alpha-carbon ¹³C-nmr chemical shift and the dihedral angle. Independent measurement of the dihedral angle in a crystallographic study has shown that there are two independent molecules contained in the assymetric unit which posess dihedral angles, Ø = 145.7 and 163.4°, the former in excellent agreement with the angle predicted by the assigned ¹³C-nmr data.     

Chemistry of the phenoxathiins and isosterically related heterocycles. X. Correlation of the dihedral angles of phenoxathiin analogs with the 13NMR chemical shifts of the sulfur bearing la carbon

The observation of a linear relationship between the ¹³C-nmr chemical shifts of the C-la carbon and the dihedral angle in a series of phenoxathiin analogs is reported. Presently available data, although limited, is presumed to be indicative of a more general behavior which has not been previously recognized or utilized. Extension of this observation to include other sulfur containing tricyclic systems may be expected to provide a useful means for the preliminary estimation of dihedral angles from solution ¹³C-nmr measurements after suitable parameterization.     

Synthesis and structural study of quinuclidine spiro derivatives

The synthesis of quinuclidine-3-spiro-5′-oxazolidine-2′,4′-dione, quinuclidine-3-spiro-5′-hydantoin, and some 3′-derivatives is described. Based on the data from ¹H and ¹³C-nmr spectra the structure of the above mentioned compounds is established. A relationship between second order effects in ¹³C-nmr spectra and H-C-C-H dihedral angles is deduced.     

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. XII. Synthesis of diazaphenoxathiin analogs: 1,9-Diazaphenoxathiin and 1,7-diazaphenoxathiin

The synthesis of the first diazaphenoxathiins, 1,9-diazaphenoxathiin and 1,7-diazaphenoxathiin, are described. Complete assignments are made for the ¹³C-nmr spectra of these compounds based on additivity correlation and ¹H-¹³C spin-coupling constants. The isolation and confirmation of the structure of 2-[2′(-3′-nitropyridylthio)]-3-[2″-(3″-nitropyridyloxy)] pyridine using ¹³C-nmr and appropriate model compounds is also discussed. A preliminary evaluation of spontaneous motor depression in mice showed a substantial difference between the observed activities of the two diazaphenoxathiins reported. The possibility of the observed difference being associated with the relative positions of the annular aza-substitutions is discussed.     

Chemistry of the phenoxathiins and isosterically related heterocycles. XI . The synthesis and 13C-NMR spectroscopy of 2-azaphenoxathiin

The synthesis of the 2-azaphenoxathiin ring system via the intermediary 2-azaphenoxathiin 2-oxide is described. Complete assignment of the ¹³C-nmr spectrum is reported, based on the observed heteronuclear ¹H-¹³C spin-couplings of the system and calculated chemical shifts as assignment criteria. The possible relation of the chemical shift of Cα to the dehidral angle of the system is also discussed.     

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.     

Vibrational analysis of the benzophenone molecule and influence of its conformation on vibrational transitions

IR and Raman spectra of benzophenone and several of its isotopomers (d_5⁻, d_l0⁻, ¹³C- and ¹³Cd₅-benzophenone) are the experimental basis for the normal coordinate analysis. The possibility of determining the conformation of the benzophenone molecule in solution from its vibrational spectrum is considered carefully. The dihedral angle between the central part of the molecule and the phenyl ring has been determined by fitting the calculated to the observed spectra. The final force field for the molecule was obtained for the dihedral angle of 35°.     

A simple graphical approach to predict local residue conformation using NMR chemical shifts and density functional theory

The dependency of amino acid chemical shifts on φ and ψ torsion angle is, independently, studied using a five‐residue fragment of ubiquitin and ONIOM(DFT:HF) approach. The variation of absolute deviation of ¹³C^α chemical shifts relative to φ dihedral angle is specifically dependent on secondary structure of protein not on amino acid type and fragment sequence. This dependency is observed neither on any of ¹³C^β, and ¹H^α chemical shifts nor on the variation of absolute deviation of ¹³C^α chemical shifts relative to ψ dihedral angle. The ¹³C^α absolute deviation chemical shifts (ADCC) plots are found as a suitable and simple tool to predict secondary structure of protein with no requirement of highly accurate calculations, priori knowledge of protein structure and structural refinement. Comparison of Full‐DFT and ONIOM(DFT:HF) approaches illustrates that the trend of ¹³C^α ADCC plots are independent of computational method but not of basis set valence shell type. © 2016 Wiley Periodicals, Inc.     

On the assignment of the 13C-NMR spectrum of phenothiazine

The assignment of the ¹³C-nmr spectrum of phenothiazine was made by comparison with the ¹³C-nmr spectrum of 1,9-dideuteriophenothiazine, synthesized via repeated lithiations and subsequent deuterations of phenothiazine.     

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.     

Nuclear magnetic resonance and the conformation of some derivatives of Michler's ketone

¹H NMR spectra are reported for Michler's ketone and twenty of its derivatives, along with ¹³C chemical shifts for five of the compounds. ¹H chemical shifts show only small changes with increasing substitution at the sterically hindered 2-position. Estimates of the dihedral angle between the benzene ring and C? CO? C planes have been obtained from the chemical shifts of C?O and 4-C for ketones 1, 3, 5, 15 and 16 . These angles are both internally consistent and very similar to dihedral angles determined by other methods for corresponding compounds in the benzophenone series.     

Chemistry of the phenoxathiins and isosterically related heterocycles. XVII. First synthesis of a benzoxathiinopyridazine and the determination of structure by 13C-NMR: 1-Methoxy-3,4-diazaphenoxathiin

The reaction of 5-methoxy-3,4-dichloropyridazine with the disodium salt of o-mercaptophenol leads to the formation of 1-methoxy-3,4-diazaphenoxathiin as the sole product of the reaction. The structure of the isolated product was confirmed by ¹³C-nmr spectroscopy, with the development of arguments to discriminate the isolated compound from 4-methoxy-1,2-diazaphenoxathiin, the other product possible in this reaction. Mechanistic considerations in the formation of the isolated product are discussed.     

Formation of heterocyclic products in michael reactions of ascorbic acid with α,β-unsaturated compounds. 3rd communication . Structural analysis of michael adducts of ascorbic acid by 13C-nmr spectroscopy in the solid state

The structure of the Michael adducts of ascorbic acid (AA) and AA-6-palmitate with acrolein can be unambiguously determined by using ¹³C-nmr solid state spectroscopy.     

The vibrational spectra and dihedral angles of biphenyl and the 4,4'-dihalogenobiphenyls

The vibrational frequencies of biphenyl and its 4,4'-dihalogen derivatives have been computed for various values of the dihedral angle between the two rings. It is shown that certain modes with frequencies below 700 cm⁻¹ are sensitive to this angle. Agreement between experimental and calculated frequencies is good. The spectra of biphenyl and 4,4'-difluorobiphenyl are in complete accord with a planar D_2h structure in the crystal phase. In solution, melt and gas the dihedral angle of these systems is 45 ± 15°. The observed frequency shifts of certain A modes are shown to be due to considerable force constant changes for the central C-C bond and its neighbouring internal angle deformations. No significant frequency shifts with phase changes were observed for 4,4'-dichloro- or 4,4'-dibromobiphenyl. In these cases the structures are D₂.     

Synthesis and characterization of stable N-phthalimidyl-2,3-butadienoates

A variety of stable, crystalline N-phthalidmidyl-2,3-butadienoates were synthesized via a Wittig reaction of the acid chloride with ethyl-2-(triphenyl-phosphoranylidene)-propionate. Both proton and ¹³C-nmr are used to confirm the allene structure.     

Preparation and some spectral properties of benzo-fused 1,4-dimethyl-2(1H)-quinolinones

The preparation of the angular and linear isomers of benzo-fused 1,4-dimethyl-2(1H)-quinolinones 3a–5a and their spectral data including ¹³C-nmr data are reported. Structural difference among 3a–5a is confirmed from the proximity effect in ¹H- and ¹³C-nmr data and from the uv spectral pattern.     

Ab-initio studies of structural features not easily amenable to experiment: 10. Correlation between thermal reactivity and equilibrium structure of tricyclo [3.1.0.02,4] hexane.

The equilibrium structure of tricyclo [3.1.0.0^2,4] hexane is computed by ab-initio methods in the 4-21G basis set with complete geometry relaxation. A correlation with thermal reactivity and with effects found in ¹³C-nmr is discussed.     

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.