A correlation of substituent effects with proton chemical shifts in aromatic tetrazolic acids

The effect of substituents on the proton chemical shifts and spin–spin coupling constants in ortho-, meta- and para-substituted 5-phenyltetrazoles (tetrazolic acids) in DMSO–CH₃CN (1:1, v/v) was studied. With the meta- and para- substituted compounds the additivity rule of chemical shifts was obeyed, thereby enabling increments characterizing the effects of individual substituents in monosubstituted benzenes to be determined. By employing the Smith and Proulx equation, the chemical shifts of the aromatic protons were correlated with the F, R and Q substituent constants. The values of these constants are 1.02, ?0.004 and 5.49, respectively, for the tetrazolyl substituent.     

Note on the relative magnitudes of substituent effects on 1H-chemical shifts in olefinic and aromatic systems

A regular relationship was noted between the influence of substituents on the chemical shifts of the ortho protons in mono-substituted benzenes and the influence of the same substituents on the protons in the cis relationship in monosubstituted ethylenes.     

Transmission of substituent effects through unsaturated systems. I—relative magnitudes of proton and carbon substituent chemical shifts in ethylenes,butadienes, α-enones and benzenes

The carbon-13 shifts of C-1, C-2 and C-3 are determined in a series of 1-cyclohexen-3-ones substituted in position 1. Linear relationships are demonstrated between the substituent chemical shifts of corresponding carbons in substituted ethylenes, butadienes, α-enones and benzenes. The substituent chemical shifts of proton H-2 are also reported and correlated with those of corresponding protons in ethylenes and benzenes. The slopes of the lines for the carbons directly linked to the substituent are close to unity, showing a relative independence of the substituent effect for this nucleus from the variation of the unsaturated framework. In contrast to this, the transmission of the substituent effect through one double bond (nuclei β to the substituents) decreases as the number of conjugated π bonds in the whole structure increases. This relationship is interpreted as being due to the ability of an unsaturated system to spread the variation of π electron density induced by the substituent.     

The proton resonance spectra of heterocycles—VI: The correlation of substituent effects on chemical shifts in bicyclic compounds

The proton chemical shifts are reported for monosubstituted naphthalenes, quinolines and quinoxalines. Together with literature data, these chemical shifts are compared with the parent compounds and substituent effects evaluated statistically. The effect of substituents parallels that in benzenes, but is modified by bond fixation, steric hindrance and other effects which can, at least qualitatively be understood. The treatment enables estimation of likely chemical shifts for ABC spectra in fused aromatic systems which should facilitate the solution of such spectra.     

Remote polar substituent effects on 13C NMR spectra of olefinic and aromatic carbons

Chemical shifts of the olefinic carbons of ω-substituted 1-pentenes and 1-butenes and the aromatic carbons of phenylethanes and phenylpropanes have been measured. Correlations with various substitutent constants, electronegativities, NMR data from related chemical systems and calculated electrical fields were evaluated. Although the pattern of results is quite consistent with expectations for a field-induced shift of π-electron density, simple correlations of high statistical precision are not found. The general problem of correlating substitutent effects with reactivity and NMR shifts is discussed.     

Determination of substituent chemical shifts in the proton resonance spectra of the porphyrins

Reproducible proton chemical shifts in the porphyrin series are obtained when the spectrum is measured in chloroform using the zinc (II) complex of the porphyrin in the presence of an excess of pyrrolidine. This method is specifically demonstrated for the case of 2,4-dicyanodeuteroporphyrin-IX dimethyl ester which, as the free base, shows dramatic effects due to aggregation phenomena. The shifts obtained using the zinc (II) complex plus pyrrolidine method, which allow compilation of substituent chemical shifts in the porphyrin series, are shown to be the same as the less easily accessible infinite dilution shifts of the porphyrin free bases.     

Excellent correlation between substituent constants and pyridinium N-methyl chemical shifts

Substituents on the pyridinium ring of N-methylpyridinium derivatives, especially those on the 2- or 4-position, have a large effect on the ¹H and ¹³C NMR chemical shifts of the N-methyl group. Reasonable correlations between the chemical shift changes and the resonance substituent constants are observed. The dual substituent parameter approach provides an excellent correlation when a combination of polar and resonance substituent constants is employed.     

Accurate prediction of proton chemical shifts. I. Substituted aromatic hydrocarbons

Forty‐five proton chemical shifts in 14 aromatic molecules have been calculated at several levels of theory: Hartree–Fock and density functional theory with several different basis sets, and also second‐order Møller–Plesset (MP2) theory. To obtain consistent experimental data, the NMR spectra were remeasured on a 500 MHz spectrometer in CDCl₃ solution. A set of 10 molecules without strong electron correlation effects was selected as the parametrization set. The calculated chemical shifts (relative to benzene) of 29 different protons in this set correlate very well with the experiment, and even better after linear regression. For this set, all methods perform roughly equally. The best agreement without linear regression is given by the B3LYP/TZVP method (rms deviation 0.060 ppm), although the best linear fit of the calculated shifts to experimental values is obtained for B3LYP/6‐311++G**, with an rms deviation of only 0.037 ppm. Somewhat larger deviations were obtained for the second test set of 4 more difficult molecules: nitrobenzene, azulene, salicylaldehyde, and o‐nitroaniline, characterized by strong electron correlation or resonance‐assisted intramolecular hydrogen bonding. The results show that it is possible, at a reasonable cost, to calculate relative proton shieldings in a similar chemical environment to high accuracy. Our ultimate goal is to use calculated proton shifts to obtain constraints for local conformations in proteins; this requires a predictive accuracy of 0.1–0.2 ppm. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 1887–1895, 2001     

稠环芳烃系列化合物化学位移的计算 IV.^1H化学位移加合性规律的量子力学基础

Based on a starting point of the McWeeny Huckel-London perturbation theory approximation, a formula similar to the fourmula of additivity rule for the calculations of the chemical shifts of condensed aromatic hydrocarbons has been derived. The quantum mechanical basis of additivity rule is thus indicated by this formula. It is shown that by using the concept of aromatic shift and sigma ratio, this method for calculation of proton chemical shifts has the virtues of definite physical meaning and simple calculation. It can also be extended to the calculation of the proton chemical shifts of substituents fr the molecules of this series.     

Additivity of proton and carbon nmr chemical shifts in protonated benzene carboxylic acids

The additivity of the proton and carbon chemical shift increments due to structural changes in a series of conjugate acids derived from benzene polycarboxylic acids is reported. In the acids, two sets of increments had been applied, one to the ortho diacids and one to acids which do not bear ortho substituents. In the conjugate acids only one set of increments is required. The disappearance of the ‘ortho’ effect may be the outcome of properties inherent to these conjugate acids.     

Correlations of chemical shifts of saturated carbon atoms that have a directly bonded substituent

The dependence of the chemical shifts, δ, of saturated carbon atoms upon the nature of the directly bonded substituent is attributed to three factors (1) electronegativity E, (2) field effect, W, and (3) heavy atom ettect, Q. Ten series of compounds (five aliphatic and five cyclic) have been correlated with the equation δ = aE + W + Q+ c where a and c are constants.     

The calculation of hydroxyl group C-13 substituent chemical shifts in steroids and other rigid systems

A four parameter equation, for the calculation of one-bond secondary OH group C-13 substituent chemical shifts in steroids and other rigid systems, is deduced from literature data by the use of a multiple regression analysis. The magnitude of the coefficients are shown to be consistent with deviations from simple additivity of C-13 shifts in various systems. Conformational information in non-rigid systems is evident from differences between the calculated and observed SCS values.     

Spatial substituent effects of various fluorinated groups on the 13C chemical shifts in cyclohexanes

The effect of introduction of fluorinated groups (CH(2)F, CHF(2), CF(3), C(2)F(5), OCF(3), SCF(3)) on the (13)C NMR chemical shifts in cyclohexanes is examined. The two main effects are caused by location at the alpha and gamma carbon positions. Comparison of the various data allowed the calculation of increments corresponding to the introduction of fluorinated groups at axial or equatorial positions on the cyclohexane ring. The introduction of fluorine atoms in methoxy and thiomethoxy groups has only a slight effect through the heteroatom on the (13)C chemical shifts.     

Group electronegativity and Fukui function studies of the substituent effects in aromatic and inorganic systems

The group electronegativities (GE ) of molecular fragments, including the environmental contributions due to both the electrostatic interactions and electron distribution relaxation, and the Fukui function (FF ) indices of the charge sensitivity analysis (CSA ) are correlated with the known substituent effects in molecular systems. The semiempirical CSA in the atoms-in-molecules (AIM ) resolution has been applied to substituted benzenes and square platinum complexes treated as illustrative examples. The calculated FF indices and GE are both shown to constitute adequate reactivity criteria that qualitatively reproduce the known substituent effects. The FF index (second-order property) is found to be a more sensitive detector of the substituent influence than is the corresponding GE parameter (first-order property). © 1992 John Wiley & Sons, Inc.     

Additive of substituent effects on the chemical shift of the formyl proton in disubstituted benzaldehydes

An additivity relationship of substituent effects on the formyl proton chemical shift has been tested with ten disubstituted benzaldehydes. In most cases it is found that the formyl proton chemical shift, extrapolated to infinite dilution in nitromethane, is in good agreement with that calculated using the additivity relationship.     

Interpretation of substituent effects on 13C and 15N NMR chemical shifts in 6-substituted purines

A range of purine derivatives modified at position 6 of the basic purine skeleton exhibit a variety of biological activities. Several derivatives are used or tested nowadays for pharmacological treatments. The present work aims to analyze the effects of substituents on the electron distribution in the purine core as reflected by NMR chemical shifts. We collected a comprehensive set of experimental NMR data for a variety of 6-substituted purines (-NH(2), -NHMe, -NMe(2), -OMe, -Me, -CCH, and -CN) and determined the molecular and crystal structures of three derivatives (-NHMe, -CCH, and -CN) by X-ray diffraction. The density-functional methods calibrated in our recent study (Phys. Chem. Chem. Phys., 2010, 12, 5126) have been employed to enable understanding of the substituent-induced changes in the NMR chemical shifts of the atoms in the purine skeleton. Analyses of the nuclear shielding using localized molecular orbitals (LMOs), specifically the natural LMOs (NLMOs) and Pipek-Mezey LMOs, were used to break down the values of the isotropic (13)C and (15)N NMR chemical shifts and the chemical shift tensors into the contributions of the individual LMOs. The experimental and calculated trends in the chemical shift of the N-3 atom correlate nicely with the Hammett constants (σ(para)) and the calculated natural charges on N-3, whereas the contributions of the LMOs to the N-1 and C-6 chemical shifts are found to be more complex.