13C NMR spectra of azolopyridines and their quaternary salts

¹³ C NMR spectra of some azole series have been investigated: 2-pyridylbenzimidazoles, 2-pyridylimidazo [4,5-b]-pyridines, 2-pyridylimidazo[4,5-c]-pyridines, analogous oxazole compounds, as well as their mono- and bisquaternary salts. Some problems, related to the structure of these compounds in solution, have been discussed.V. I. Vernadskii Institute of Geochemistry and Analytical Chemistry, Russian Academy of Sciences, Moscow 117975. Torino University, Italy. Translated from Izvestiya Akademii Nauk, Seriya Khimicheskaya, No. 4, pp. 866–872, April, 1992.     

13C chemical shifts and conformational analysis of S-methylthiolanium cations

The ¹³C NMR spectra of all cations obtained by methylation at sulphur of the mono-and dimethylthiolanes are reported. The methyl substituent on sulphur affects the shieldings of the adjacent carbons in a manner which allows easy identification of the cis and trans isomers. For most compounds the ¹³C pattern is consistent with a half-chair ring conformation with maximum staggering at C-3, C-4. Only with methyl groups at the 1,2-or 1,2,3-positions is the half-chair appreciably deformed. It is suggested that in these cases the preferred conformation is a quasi-envelope with C-3 at the top.     

The temperature dependence of 13C NMR shifts in polar compounds and its role for the determination of conformational equilibria

Intrinsic temperature dependencies of ¹³C NMR shifts in alkanes bearing one polar C-α? X bond are determined with neopentyl and 4-tert-butylcyclohexyl derivatives as conformationally homogeneous model compounds. The increased shiedling for C-α at higher temperatures can be related to a C-α—X bond length increase and, for less polarizable C? X bonds, essentially to a decrease of solvent polarity on raising the temperature. The use of temperature dependent ¹³C shifts in conformationally mixed compounds for the determination of the equilibrium constants, K, is evaluated with n-propyl halides; the computer fit of the unknown conformer shifts and the conformational enthalphy difference, δH° to the time averaged shifts yields δH° values which, although converging rather broadly, are in general agreement with literature data. In compounds with higher conformational barriers, such as methoxy- and bromocyclohexane, low temperature signal integration yields accurate δG° values; inclusion of shifts above coalescence, however, yields unreliable δH° and δS° parameters. This can only partially be remedied by application of temperature shift corrections obtained from parent t-butylcyclohexyl compounds.     

14N chemical shifts in the enamino ketone quaternary ammonium salts

The ¹⁴N chemical shifts were measured for a series of quaternary ammonium salts of enamino ketones. An upfield shift of the ¹⁴N resonance signals upon quaternization has been observed. The interpretation in terms of the approximate theory of nuclear magnetic shielding is given. The calculations for some model systems result in a general agreement with the experimental data.     

Conformations and 13C NMR shifts in tetralins

Force field (MM2) calculations, ¹³C NMR substituent-induced shifts (SIS) and epimeric shift differences (ESD) indicate a preference for equatorial substituents in the 2-position, but equal eq/ax populations in the 1-position of tetralines. Similar conclusions are reached from Yb(fod)₃-induced shifts, which are also used for signal assignments, e.g. in 1-tetralone. Configurational assignments are possible for 1,2- and 1,3-epimers (ESD up to 4 ppm) but, in line with the non-discriminating eq/ax conformations at C-I, not for 1,4-epimers (ESD<0.5 ppm). More than 50 compounds were measured, including functional derivatives which show regular SIS for substituents in the aromatic moiety only for m- and p-carbon atoms. OMe, but not OH or OAc substituents, induce o-carbon SIS varying from ?11 to ?19 ppm. Conversion of 1-hydroxytetralin to esters induces shielding variations at the aromatic carbon atoms which indicate the electrostatic origin of derivatization shifts.     

13C nuclear magnetic resonance studies of saturated heterocycles: II—substituent effects on the 13C chemical shifts of methyl substituted 1,3-dithianes and their application to the determination of conformational equilibria

The ¹³C chemical shifts for 1,3-dithiane and 9 methyl substituted derivatives are reported. Only three of the methyl-1,3-dithianes were conformationally anancomeric and hence the conformational equilibria must be taken into account when deriving the values of the different substituent effects on the ¹³C chemical shifts. The best fit for each substituent effect was obtained when –ΔG^θ (5a-Me) for 5-methyl-1,3-dithiane was given the value 3.8 ± 0.3 kJ mol^?1 and when the difference between –ΔG^θ (2a-Me) and –ΔG^θ (5a-Me) for cis-2,5-dimethyl 1,3-dithiane equalled 3.4 ± 0.4 kJ mol^?1. The conformer populations chosen from our earlier paper¹ were then suitable for all the other conformational equilibria in question. The magnitude of the derived substituent effects are compared with those for cyclohexane and 1,3-dioxane.     

Correlation of dihedral angles with 13C chemical shifts of quaternary carbon atoms of some phenothiazine derivatives

A direct relationship between the ¹³C nmr chemical shifts of the quaternary carbon atoms of the central ring of phenothiazine and the dihedral angle of the respective derivatives has been observed. This correlation allows for the useful and quick estimation of the dihedral angles of novel phenothiazines from readily obtainable ¹³C nmr solution measurements. In addition, the change in the dihedral angle appears to be directly related to the S-C_4a-C_10a bond angle; however, the C_4a-S-C_5a bond angle is not affected by changes in the dihedral angle. This indicates that the “flattening” of the phenothiazine tricyclic ring system is compensated for by the vertical displacement of the sulfur atom, by changes in hybridization of N₁₀, and by other angular distortions of the middle ring.     

Chemical ionization desorption mass spectrometry of some quaternary ammonium salts

The ammonia chemical ionization desorption spectra of N,N-dimethyl quaternary ammonium iodides in addition to high protonated molecular ion [M + H]⁺ intensity, show signals for an ion radical composed of N-methyl abstracted salt cation and ammonia [C + NH₃? CH₃]^+˙. These ions corresponding to the cation +2 show increased importance in the chemical ionization mode, using the same reagent gas. The technique of chemical ionization desorption appears suitable for the analysis of salts, and thus for the determination of the molecular weight of both anion and cation.     

Deuterium isotope effect on 13C chemical shifts of tetrabutylammonium salts of Schiff bases amino acids

Deuterium isotope effects on 13C chemical shift of tetrabutylammonium salts of Schiff bases, derivatives of amino acids (glycine, L-alanine, L-phenylalanine, L-valine, L-leucine, L-isoleucine and L-methionine) and various ortho-hydroxyaldehydes in CDCl3 have been measured. The results have shown that the tetrabutylammonium salts of the Schiff bases amino acids, being derivatives of 2-hydroxynaphthaldehyde and 3,5-dibromosalicylaldehyde, exist in the NH-form, while in the derivatives of salicylaldehyde and 5-bromosalicylaldehyde a proton transfer takes place. The interactions between COO- and NH groups stabilize the proton-transferred form through a bifurcated intramolecular hydrogen bond.     

13C nmr determination of the conformational equilibria in the acetates,benzoates and n-phenylcarbamates of 1-methylcyclohexanol and cyclohexanol

Thermodynamic parameters for the confonnatinal equilibria in the acetates, benzoates and N-phenylcarbamates of 1-methylcyclohexanol and cyclohexanol have been determined using low temperature natural abundance¹³C nmr, from which -ΔG° values at room temperature and above are obtained. Good agreement between these values and those determined at the higher temperatures using Eliels method is found, providing care is exercised in correcting the chemical shifts of the model compounds used to find the shifts of pure confomers of the 1,1-disubstituted cyctohexanes. Calculated values for -ΔG° agree reasonably with experimental values with the exception of that for the 1-methylcyclohexyl N-phenylcarbanate. The effect of non polar solvent changes is minimal, but greater for CD₃OD.     

13C NMR spectra of 1,3-dipyridyl- and pyridylphenylthioureas. Chemical shift assignments and conformational implications

The ¹³C NMR spectra of a series of 1,3-dipyridyl- and pyridylphenylthioureas have been obtained. Complete analyses of the experimental spectra have provided the chemical shifts and coupling constants. The spectra of dipyridylthioureas over a temperature range showed important changes which could be attributed to an intramolecular conversion between the two equivalent E,Z and Z,E conformations. The coalescence temperature of the ¹³C signals leads to a ΔG* of ∼ 58.0 kJ mol⁻¹ for the dynamic process involved. The results show that pyridylphenyl thioureas exist in a single conformation at ambient temperature.     

Dependence of amino acid side chain 13C shifts on dihedral angle: application to conformational analysis

Chemical shift data from the BiomagResDataBank and conformational data derived from the protein data bank have been correlated in order to explore the conformational dependence of side chain (13)C resonance shifts. Consistent with predictions based on steric compression, upfield shifts for Cgamma resonances of Thr, Val, Ile, Leu, Met, Arg, Lys, Glu, and Gln residues correlate with both the number of heavy atom (nonproton) gamma-substituents and with gauche conformational orientations of gamma-substituents. The (13)C shift/conformation correlations are most apparent for Cgamma carbons but also can be observed at positions further from the backbone. Intraresidue steric conflict leads to a correlation between upfield-shifted side chain (13)C resonances and statistically lower probabilities in surveys of protein side chain conformation. Illustrative applications to the DNA pol lambda lyase domain and to dihydrofolate reductase are discussed. In the latter case, (13)C shift analysis indicates that the conformation of the remote residue V119 on the betaF-betaG loop is correlated with the redox state of the bound pyridine nucleotide cofactor, providing one basis for discrimination between substrate and product. It is anticipated that (13)C shift data for protein sidechains can provide a useful basis for the analysis of conformational changes even in large, deuterated proteins. Additionally, the large dependence of the leucine methyl shift difference, deltaCdelta1-deltaCdelta2, on both chi1 and chi2 is sufficient to allow this parameter to be used as a restraint in structure calculations if stereospecific assignment data are available.     

Utility of calculated 13C NMR chemical shifts in differentiating conformational isomers: a study of metal-complexed and uncomplexed bispidines

Calculated 13C NMR chemical shifts were key to assigning the structures of the conformational forms of complexed and uncomplexed bispidine derivatives.     

13C n.m.r. of organosulphur compounds: II—13C chemical shifts and conformational analysis of methyl substituted thiacyclohexanes

¹³C n.m.r. spectra of methyl substituted thianes and thianium cations have been determined. The magnitude of the ¹³C substituent effects of an equatorial methyl group or of a gem-dimethyl grouping appear to depend in a systematic way on whether the carbon atom concerned is adjacent to, or removed from, the heteroatom. The shieldings are discussed in relation to the conformational properties of the thiane ring. Moreover, the average ¹³C substituent parameters obtained from conformationally biased systems are applied to potentially mobile systems to assess the position of the conformational equilibrium.     

13C chemical shifts of monosubstituted adamantanes

¹³C chemical shifts are reported for adamantane, nine 1-substituted adamantanes and nine 2-substituted adamantanes. The substituents are F, Cl, Br, I, NH₂, OH, CH², CN and CO₂H. The assignments and results are discussed in terms of chemical shift patterns.     

Alkylbenzonaphthyridinones and benzonaphthyridinium quaternary salts

Four methyl and ethylbenzonaphthyridinones, along with two ethylbenzonaphthyridinium iodides, 2.5-dimethyl-1,5-benzo[c]naphthyridinium iodide, as well as three isomeric N-3-bromopropylbenzonaphthyridinium bromides have been synthesized and their structures confirmed by¹H NMR spectroscopy. Biological data (minimal inhibitory concentrations) for two of the obtained compounds are presented.Institute of Chemistry, Pedagogical University, 42-201 Czestochowa, Poland Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 7, pp. 944–950, July, 2000.     

13C NMR Chemical shifts in bicyclo[2.2.2]octanes—iii: Hydroxy acids and lactones

A number of hydroxybicyclo[2.2.2]octane carboxylic acids and the corresponding delta lactones have been prepared, and the ¹³C NMR spectra show trends that, together with some deuteration experiments, provide a self consistent and unambiguous assignment of the resonance peaks. The effects produced by the substituents and the changes in chemical shifts brought about by the lactonization process are analysed.