Application of 1H and 13C NMR to the structural elucidation of tetrahydroquinoxalines condensed with five-membered heterocycles

¹H and ¹³C NMR spectral data for 21 N-methyltetrahydroquinoxalines annelated with furan, pyrrole, imidazole or thiazole rings are reported. Unambiguous assignments of the ring junction ¹³C resonances were made on the basis of selective decoupling experiments and with the aid of one-bond and long-range ¹³C–¹H coupling constants. The effects of five-membered heterocycles on the ¹H and ¹³C chemical shifts of the ring junction hydrogen and carbon atoms are considered. Values of one-bond ¹J(CH) and vicinal ³J(HH) coupling constants between the ring junction protons are also discussed as a diagnostic means for structural elucidation of tetrahydroquinoxalines condensed with five-membered heterocycles.     

Carbon-13 NMR studies of monohydroxylated and monochlorinated derivatives of Z- and E-p-menthanes

J(¹³C¹H) coupling constants for some methyl- and aminopyrimidines have been determined by ¹³C NMR. Both the one-bond and long-bond and long-range coupling constants follow general trends which can be summarized in a few simple rules. In particular, the ³J(C-i,H) coupling constants between a ring carbon C-i and the ring protons are larger than the ²J(C-i,H) coupling constants. The opposite is observed for the couplings between the ring carbons and the methyl protons: ³J(C,Me). These general rules are very useful for the assignment of resonances in complex ¹³C spectra of pyrimidines and seem to be valid for other 6-membered aromatic nitrogen heterocycles. Furthermore, the additivity of substituent effects on ¹J (CH) for monosubstituted pyrimidines allows the estimation of ¹J (CH) for polysubstituted pyrimidines with a very good accuracy.     

15N NMR spectroscopy 24—chemical shifts and coupling constants of α-amino acid N-carboxyanhydrides and related heterocycles

The chemical shifts of amino acid N-carboxyanhydrides (NCAs) and cyclic or linear urethanes are less sensitive to solvent effects than those of amides and lactams. The values of the one-bond ¹⁵N? ¹H coupling constants depend on the solvent and are 5-8 Hz larger than those of ureas and amides. The ¹⁵N? ¹³C coupling constant of the N? CO group is also unusually high, while that of the N—CH group lies within the range known for N-acylated aliphatic amines. The one-bond ¹⁵N? ¹³C coupling constant was found to be insensitive to conformational changes.     

15N-NMR study of activated enamines. Structural dependence of δ (15N) and nJ(N,H) in primary,secondary and tertiary enamino-ketones,esters and amides

The pulse sequence INEPT was used to obtain proton-coupled ¹⁵N-NMR spectra in natural isotope abundance for enamines substituted in 2-position with electron-with-drawing groups. The chemical shifts and coupling constants are discussed in terms of their relationship to structural features such as multiple N-alkyl substitution, double-bond configuration, H-bonding, N-lone-pair delocalization within the conjugated system, and steric effects. It is concluded that ¹⁵N chemical shifts are a sensitive probe for local structural modifications at the N-atom and conformational changes in a remote part of a conjugated molecule, while one-bond N,H-coupling essentially reflects N-hybridization and subtle local geometric distortions. Stereospecific three-bond N,H spin coupling to olefinic protons (4.0 ± 0.2 Hz) has been found a characteristic feature of (Z)-isomers in all investigated compounds, whereas two-bond coupling to olefinic protons (²J(N,H) = 0.5 to 5 Hz) is observed in (E)-isomers. The sensitivity to solvents and steric properties of remote substituents renders geminal coupling a useful probe for studying electronic effects in the C? N bond.     

13C NMR study of some polychloro-isobutane and -isobutene compounds

The ¹³C chemical shifts and the carbon–proton coupling constants have been determined for some chlorinated isobutane and isobutene compounds. The one-bond coupling constants in isobutane derivatives showed a regular increase with an increasing number of γ-chlorine substituents. The three-bond coupling constant of the methyl carbon decreased from 4.2 to 2.0 Hz as the number of chlorine substituents in the γ-position increased. In the isobutene compounds, the vicinal coupling of C-1 was larger to protons in a group that is trans with respect to a chlorine substituent on C-1 than to those in the corresponding group cis to the chlorine. The vicinal coupling constants between atoms in geminal groups (on C-2) seem to be affected by the orientation of the chlorine substituent on C-1.     

13C?13C spin coupling constants in tetrahydronaphthylene,hexahydrobenzanthracene and benzo[a]pyrene derivatives

The ¹³C? ¹³C spin coupling constants have been determined in substituted [1-¹³C]tetrahydronaphthylenes, [5-¹³C]hexahydrobenzanthracenes and [5-¹³C]benzanthracene. In addition, the ¹³C? ¹³C spin coupling constants for 7-hydroxy[7-¹³C]benzopyrene, trans-7,8-dihydro[7-¹³C]benzopyrene-7,8-diol and trans-7,8-dihydro[10-¹³C]benzopyrene-7,8-diol are reported, together with the one-bond carbon-carbon coupling constants between C-4 and C-5 in selected 4,5-disubstituted benzopyrenes. Values for the directly bonded coupling constants and long-range coupling constants are similar to those reported previously for other aromatic and aliphatic systems. Substituent effects on carbon-carbon coupling are compared for similarly substituted cyclic and acyclic systems.     

13C NMR spectra of benzo[b]thiophene and 1-(X-benzo[b]thienyl)ethyl acetate derivatives

Carbon-13 chemical shift assignments are reported for benzo[b]thiophene and 1-(X-benzo[b]thienyl)ethyl acetate derivatives, where X=? CH(OAc)CH₃ substituted at positions 2-7. Substituent chemical shift (SCS) effects for the ethyl acetate group are additive at all positions. A substantial upfield shift was observed at C-3, arising from the peri interaction of H-3 and the 4-ethyl acetate substituent. Carbon-13 relaxation times (T₁) and nuclear Overhauser enhancements (η) have been measured for benzo[b]thiophene and its derivatives, and the contributions of dipolar, T^DD₁, and spin rotation, T^SR₁, relaxation have been determined. Intramolecular dipole–dipole interactions are found to provide by far the most important spin-lattice relaxation mechanism whenever protons are bound directly to the carbons under investigation. Nonprotonated ring carbons are relaxed by both DD and SR mechanisms. Anisotropic motion has an easily observable effect on the DD contribution to T₁, and can form the basis for spectral assignments, as in 1-phenylethyl acetate. Long-range ¹³C? ¹H coupling constants were observed both between ring carbons and between ring carbons with ring side-chain hydrogens. These results have been used for the structure determination of the title compounds.     

Unexpected second-order effects in proton-coupled 13C NMR spectra

‘Unexpected’ second-order effects encountered in proton-coupled ¹³C NMR spectra where relative proton shifts are large compared to proton-proton coupling constants are illustrated. The observed phenomenon is explained, with reference to the ABX spin system as a model, as being due to the near equality of the relative proton shift, in frequency units, to the difference between one-bond and long-range ¹³CH couplings. The effect may be removed by a change in operating field strength or addition of a shift reagent.     

Carbon-13 NMR studies of twenty-four methyl-substituted morpholines

Carbon-13 NMR spectra of all the isomers of monomethyl-, 2,3-, 2,5-, 2,6-, 3,5-dimethyl-, 2,3,5-, 2,3,6-trimethyl- and 2,3,5,6-tetramethylmorpholine have been obtained at both ambient (25 °C) and low temperature (～ ?100 to ?120 °C). The ring carbon shifts appear to be additive with respect to the position of the methyl groups. A good correlation between predicted and experimental shift values was obtained (r = 0.998₉). The values were used in an attempt to assign, conformationally, the ‘all cis’ isomer 2,3,5,6-tetramethylmorpholine, which from ¹HNMR spin–spin coupling studies has been unsuccessful. Methyl carbon shifts to high field were found for axially oriented carbons. The extracted ‘steric shift’ values for such carbons were compared to their corresponding proton shift data.     

Determination of one-bond 14N?13C coupling constants in amines using 13C T1ρ measurements

¹³C T_1ρ values measured for isobutylamine, diethylamine, pyrrolidine, piperidine and triethylamine yield one-bond ¹⁴N? ¹³C coupling constants and ¹⁴N spin-lattice relaxation times. A decrease of ¹J(¹⁴N¹³C) was observed in sterically hindered secondary amines.     

13C NMR spectra of benzothiazepinone,benzothiazinone and benzosulphonamide N-substituted derivatives

A comparative study of the ¹³C NMR spectra of benzothiazinone and benzothiazepinone dioxide derivatives and of some structurally related benzosulphonamides is presented. The size of the heterocyclic ring is reflected in the ¹³C chemical shifts and in the one-bond carbon-proton aromatic coupling constants. An upfield γ-effect of sulphur on the ¹³C chemical shifts in N-substituted carboxyethylbenzene-4,5-dimethoxysulphonamides is reported.     

13C nuclear magnetic resonance of organophosphorus compounds XI—aminophosphines

Natural abundance ¹³C NMR studies have been carried out on a series of organophosphorus compounds possessing P? N bonds. For the first time a one-bond temperature-dependent ¹³C—³¹P nuclear spin coupling was observed for the P-phenyl carbons in bis(N,N-dibenzylamino)phenylphosphine (0-9 Hz) and bis(N,N-diethylamino)phenylphosphine (0–2 Hz). This temperature-dependent behavior can be rationalized in terms of free rotation about the phenyl phosphorus bond with concomitant hindered rotation about the P? N bonds. A conformational preference for the nitrogen and phosphorus lone pairs to exist in the trans orientation is indicated. In the similarly substituted 5-membered heterocyclic ring compound, 1,3-dimethyl-2-phenyl-1,3-diazaphospholidine, the phenyl one-bond coupling increases to (?) 42.1 Hz and becomes temperature independent. These data suggest that ¹J(PC) is very responsive to electronic effects.     

1H n.m.r. spectra of N-phenylmaleimide in isotropic and nematic phases

¹H n.m.r. spectra of N-phenylmaleimide have been investigated in isotropic as well as nematic phases; the chemical shifts, the direct dipolar and the indirect spin–spin coupling constants have been determined. The direct dipolar coupling constants are consistent with rapidly interconverting energetically equivalent twisted conformations of C₂ symmetry. Under the assumption that only two such conformers are predominantly present, the angle between the phenyl and the maleimide planes is determined as 52.9±0.9°.     

Modeling of heavy-atom-ligand NMR spin-spin coupling in solution: molecular dynamics study and natural bond orbital analysis of Hg-C coupling constants

Ab initio molecular dynamics (MD) and relativistic density functional NMR methods were applied to calculate the one‐bond Hg? C NMR indirect nuclear spin–spin coupling constants (J) of [Hg(CN)₂] and [CH₃HgCl] in solution. The MD averages were obtained as J(¹⁹⁹Hg? ¹³C)=3200 and 1575 Hz, respectively. The experimental Hg? C spin–spin coupling constants of [Hg(CN)₂] in methanol and [CH₃HgCl] in DMSO are 3143 and 1674 Hz, respectively. To deal with solvent effects in the calculations, finite “droplet” models of the two systems were set up. Solvent effects in both systems lead to a strong increase of the Hg? C coupling constant. From a relativistic natural localized molecular orbital (NLMO) analysis, it was found that the degree of delocalization of the Hg 5d_σ nonbonding orbital and of the Hg? C bonding orbital between the two coupled atoms, the nature of the trans Hg? C/Cl bonding orbital, and the s character of these orbitals, exhibit trends upon solvation of the complexes that, when combined, lead to the strong increase of J(Hg? C).     

The carbon-13 chemical shifts and the analysis of the relaxation times T1 and long range 13C−1H coupling constants of quinoline and of 1-(X-quinolyl)ethyl acetate derivatives

The ¹³C chemical shifts and the ¹³C−¹H coupling constants of quinoline (1-(X-quinolyl)ethyl acetate derivatives (where X=−CH(OAc)CH₃ substituted at positions 2,4,5–8) are reported. Substituent chemical shift (SCS) effects for the ethyl acetate group are additive at all positions. A substantial upfield shift of 4.5 and 4.8 ppm was observed at C-4 and C-5, arising from the peri interaction of 5- and 4-ethyl acetate substituents respectively. A vicinal (peri) ³J CCCH coupling constant of approximately 5 Hz is observed between both C₅−H₄ and C₄−H₅. Carbon-13 relaxation times (T₁) and nuclear Overhauser enhancements (η) have been measured for quinoline and its derivatives, and the contributions of dipolar, T₁^DD, and spin rotation, T₁^SR, relaxation have been determined. Intramolecular dipole-dipole interactions are found to provide by far the most important spin-lattice relaxation mechanism whenever protons are bound directly to the carbons under investigation. Non-protonated ring carbons are relaxed by both DD and SR mechanisms. Anisotropic motion has an easily observable effect on the DD contribution to T₁, and can form the basis for spectral assignments, as in 1-phenylethyl acetate. Long-range ¹³C−¹H coupling constants were observed both between ring carbons and between ring carbons with ring side-chain hydrogens. These results have been used for the structure determination of the title compounds.     

19F coupling constants and chemical shifts in some dimethylamino and alkoxy derivatives of tellurium hexafluoride,cis TeF4XY

The spectra of A₂BC spin systems provided by the ¹⁹F nuclei in cis (RO) (MeO)TeF₄ and (RO) (Me₂N)TeF₄ (R = Me, Et, Pr, i-Pr) have been recorded and analysed. The geminal coupling constants ²J(F,F) range from 137–174 Hz and trends in the ¹⁹F chemical shifts permit complete assignment of the resonances. Stereospecific coupling between ¹⁹F and the protons of the N-methylamino groups is also observed.     

STRONG INADEQUATE,an experiment for detection of small J(C,C) couplings in symmetrical molecules

A new version of the two-dimensional INADEQUATE experiment was designed for detection of small couplings between equivalent carbon atoms separated in the molecule by several bonds, where other techniques fail due to rich line splitting and mutual peak cancellation in many molecules. As the proposed method is suitable for detection of couplings in strongly coupled systems in general, we propose the name STRONG INADEQUATE in the paper. Similar to other methods for detection of couplings between equivalent carbons, the STRONG INADEQUATE experiment utilizes one-bond carbon–proton coupling for creation of the effective chemical shift differences. The STRONG INADEQUATE experiment works superbly for ⁿJ_CC, where n ≥ 3. Then the F1 pattern is reduced to a simple antiphase doublet with ⁿJ_CC separation, and this pattern is also preserved when a symmetrical HC···C′H′ system is coupled to other protons. Even in the measurement of ²J_CC couplings, the STRONG INADEQUATE experiment generates a much simpler pattern than the original pulse sequences for measurement of couplings between equivalent carbons.     

Carbon-13 NMR spectra of monosubstituted pyrazines

Carbon-13 NMR chemical shifts and one-bond carbon–hydrogen coupling constants have been obtained at 15·09 MHz. The trends in the carbon chemical shifts obtained for the pyrazines parallel those of monosubstituted benzenes and 2-substituted pyridines, except for the direct effect of substitution where the pyrazines resemble pyridines not benzenes. The substituent effects on the ¹³C NMR spectra are generally quite similar to those in the ¹H NMR spectra. The ¹³C NMR spectrum of the tautomeric hydroxypyrazine has been compared with the ¹³C NMR spectra of 2-, 3- and 4-hydroxypyridines. Hydroxy compounds that can exist as a cyclic amide show a large meta substituent effect on the chemical carbon shift.     

A NMR investigation of proline and its derivatives. II—Conformational implications of the 1H NMR spectrum of L-proline at different pH

The 250 MHz ¹H NMR spectrum of L -proline is comprehensively analysed by computer simulation for different pH values. A fast endo–exo interconversion has already been proposed from chemical shift and coupling constant data. A critical comparison of the vicinal coupling constants leads to the conclusion that in basic solution the equilibrium is shifted towards a more endo conformation. The position of the carboxylic plane in the ring space is given by the relative intramolecular chemical shift of the geminal protons and by the typical patterns of the H_α multiplet. These results are applied to the analysis of the spectra of Pro? NH₂ and Ac? Pro? NH₂.     

Heteronuclear multiple magnetic resonance studies of quaternary ammonium salts derived from heterocyclic bases

¹⁴N tickling experiments performed with simultaneous decoupling of substituent protons are used to show that ²J(¹⁴N? H_ortho) and ³J(¹⁴N? H_meta) are both positive in the N-methyl pyridinium ion and related species. Long range coupling extending over as many as five bonds is observed between N-methyl protons and ring protons in ¹⁴N-decoupled spectra. Triple resonance decoupling is used to permit an analysis of the AA′MM′ spin system given by the ring proton of N-methyl pyrazinium iodide.