Hydroacridines: part 29. 15N NMR chemical shifts of 9-substituted 1,2,3,4,5,6,7,8-octahydroacridines and their N-oxides-Taft, Swain-Lupton, and other types of linear correlations

The (15)N NMR chemical shifts of 1,2,3,4,5,6,7,8-octahydroacridine, 12 of its 9-substituted derivatives, and of the corresponding N-oxides were measured and examined in terms of the 9-substituent effects and the effects of N-oxidation. For the 9-substituent effects, good linear correlations were found with the Taft and Swain-Lupton substituent constants, for both octahydroacridines and their N-oxides. The (15)N chemical shifts of both octahydroacridines and their N-oxides also correlate well, linearly with the (13)C chemical shifts of the para-carbons in analogously substituted benzene derivatives.Within the studied compounds, the magnitudes of the N-oxidation effects range from - 16.4 to - 27.4 ppm (shielding), and also correlate linearly with the Taft and Swain-Lupton substituent constants, as well as with the bond orders of the N(+)-O(-) bonds in the corresponding N-oxides. Furthermore, a very good linear correlation is found between the (15)N chemical shifts of octahydroacridines and those of the corresponding N-oxides. From the (15)N chemical shifts data, the Taft and Swain-Lupton substituent constants for the diacetylamino group (-NAc(2)) were evaluated in the present paper, as follows: sigma(R) = 0.07 and sigma(I) = 0.15; R = 0.08 and F= 0.20.     

1H chemical shifts in NMR: Part 23, the effect of dimethyl sulphoxide versus chloroform solvent on 1H chemical shifts

The 1H chemical shifts of 124 compounds containing a variety of functional groups have been recorded in CDCl3 and DMSO-d6 (henceforth DMSO) solvents. The 1H solvent shift Delta delta = delta(DMSO) - delta(CDCl3) varies from -0.3 to +4.6 ppm. This solvent shift can be accurately predicted (rms error 0.05 ppm) using the charge model of alpha, beta, gamma and long-range contributions. The labile protons of alcohols, acids, amines and amides give both, the largest solvent shifts and the largest errors. The contributions for the various groups are tabulated and it is shown that for H.C.C.X gamma-effects (X = OH, NH, =O, NH.CO) there is a dihedral angle dependence of the gamma-effect. The group contributions are discussed in terms of the possible solvent-solute interactions. For protic hydrogens, hydrogen bonding is the dominant interaction, but for the remaining protons solvent anisotropy and electric field effects appear to be the major factors.     

Complete 1H, 13C and 15N NMR assignment of tirapazamine and related 1,2,4-benzotriazine N-oxides

1H, 13C and 15N NMR measurements (1D and 2D including 1H--15N gs-HMBC) have been carried out on 3-amino-1, 2,4-benzotriazine and a series of N-oxides and complete assignments established. N-Oxidation at any position resulted in large upfield shifts of the corresponding N-1 and N-2 resonances and downfield shifts for N-4 with the exception of the 3-amino-1,2,4-benzotriazine 1-oxide in which a small upfield shift of N-4 was observed. Density functional GIAO calculations of the 15N and 13C chemical shifts [B3LYP/6-31G(d)//B3LYP/6-311+G(2d,p)] gave good agreement with experimental values confirming the assignments. The combination of 13C and 15N NMR provides an unambiguous method for assigning the 1H and 13C resonances of N-oxides of 1,2,4-benzotriazines.     

The prediction of (1)H chemical shifts in amines: a semiempirical and ab initio investigation

Twenty one conformationally fixed amines and their N,N-dimethyl derivatives were obtained commercially or synthesized. These included cis and trans 4-t-butyl cyclohexylamine, 2-exo and 2-endo norbornylamine, 2-adamantylamine, 4-phenylpiperidine, 1-napthylamine and tetrahydro-1-napthylamine. The (1)H NMR spectra of these amines were measured in CDCl(3) solution, assigned and the (1)H chemical shifts given. This data was used to investigate the effect of the amino group on the (1)H chemical shifts in these molecules. These effects were analyzed using the CHARGE model. This calculates the electric field and steric effects of the amino group for protons more than three bonds removed, together with functions for the calculation of two-bond and three-bond effects. The rotational isomerism about the C--N bond of the amino group was investigated by ab initio calculations of the potential energy surface (PES) about this bond at the HF/3-21G level. The resulting conformers were then minimized at the B3LYP/6-311 + + G (d,p) level. These geometries were then used to calculate the (1)H chemical shifts in the above compounds by CHARGE and the ab initio gauge-invariant atomic orbital (GIAO) method at the B3LYP/6-311 + + G(d,p) level and the shifts were compared with those observed. The compounds investigated gave 170 (1)H chemical shifts ranging from 0.60 to 8.2 ppm. The rms errors (obs.-calc.) were ca 0.1 ppm (CHARGE) and ca 0.2 ppm (GIAO). Large deviations of ca 1.0 ppm were observed for the NH protons in the GIAO calculations. The complex spectra of alkyl and aryl amines can thus be successfully predicted by both ab initio and semiempirical methods except for the NH protons, for which the ab initio calculations are not sufficiently accurate.     

A study of the 15N NMR chemical shifts in substituted anilines and phenylhydrazines, and their derivatives

The analysis of (15)N chemical shift data from over a hundred anilines, N-methyl anilines, N,N-dimethyl anilines and phenylhydrazines with substituents in the phenyl ring leads to an empirical equation, delta(cal) = deltaon + Deltao + Deltam + Deltap, for calculating (15)N NMR chemical shifts of the amino group. This equation is based on a linear regression analysis using eighteen substituent parameters and leads to good conformity with the expected data.     

Predicting 15N amide chemical shifts in proteins. I. An additive model for the backbone contribution

Because proteins adopt unique structures, chemically identical nuclei in proteins exhibit different chemical shifts. Amide ¹⁵N chemical shifts have been shown to vary over 20 ppm. The cause of these chemical shift inequivalencies is the different intra‐ and intermolecular interactions that individual nuclei experience at different locations in the protein structure. These chemical shift inequivalencies can be described as structural shifts, the difference between the actual chemical shift and the random coil chemical shift. As a first step toward the prediction of these amide ¹⁵N structural shifts, calculations have been carried out on acetyl‐glycine‐methyl amide to examine how a neighboring peptide group influences the amide ¹⁵N structural shifts. The ϕ,ψ dihedral angle space is completely surveyed, while all other geometrical variables are held fixed, to isolate the effect of the backbone conformation. Similar calculations for a limited number of conformations of acetyl‐glycine‐glycine‐methyl amide were carried out, where the effects of the two terminal peptide groups on the central amide ¹⁵N structural shift are examined. It is shown that the effect of the two adjacent groups can be accurately modeled by combining their individual effects additively. This provides a quite simple method to predict the backbone influence on amide ¹⁵N structural shifts in proteins. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 366–372, 2001     

Additive chemical shift parameters for methylene protons. Shoolery's constants reinvestigated

Methylene proton chemical shifts have been studied using multiple linear regression analysis, and additive chemical shift parameters have been determined. Using a data set of 1007 chemical shifts, involving 48 different substituents, a standard error of estimate of 0.15 ppm was found for protons spread between 2.0 and 5.9 ppm. Provision was made in the data matrix for substituent effects for directly attached groups (α) and for groups attached via one intervening saturated carbon (β-substituents). The influence of groups more remotely located was assumed to be negligible. Although the parameters were optimized for deshielded methylene proton shifts, they also serve satisfactorily for the estimation of shifts in more shielded methylene cases.     

Substituent effects on 15N NMR chemical shifts in selected N-alkylthiohydroxamic acids. A comparative study

The 15N NMR spectra of three N-alkyl-delta-carbomethoxyvalerothiohydroxamic acids (2) and six synthesized N-isopropylbenzothiohydroxamic acids (3) were measured and compared with appropriate spectra of structurally similar hydroxylamines (1), benzohydroxamic acids (4), benzamides (5) and thiobenzamides (6). The analysis of the chemical shifts of the thiohydroxamic acids under investigation indicates that the inductive effect of the hydroxyl group rather than steric hindrance is responsible for non-additivity of the effect of substituents. Additionally, N-hydroxyl diminishes the effect of aromatic ring substituents on the 15N chemical shifts in the thiohydroxamic acids 3 which is approximately half that in the respective thiobenzamides 6. The chemical shift values correlate best with Brown's sigma+ parameter.     

Experimental and quantum-chemical studies of 1H, 13C and 15N NMR coordination shifts in Pd(II) and Pt(II) chloride complexes with quinoline, isoquinoline, and 2,2'-biquinoline

1H, 13C, and 15N NMR studies of platinide(II) (M=Pd, Pt) chloride complexes with quinolines (L=quinoline-quin, or isoquinoline-isoquin; LL=2,2'-biquinoline-bquin), having the general formulae trans-/cis-[ML2Cl2] and [M(LL)Cl2], were performed and the respective chemical shifts (delta1H, delta13C, delta15N) reported. 1H coordination shifts of various signs and magnitudes (Delta1Hcoord=delta1Hcomplex-delta1Hligand) are discussed in relation to the changes of diamagnetic contribution to the relevant 1H shielding constants. The comparison to the literature data for similar complexes containing auxiliary ligands other than chlorides exhibited a large dependence of delta1H parameters on electron density variations and ring-current effects (inductive and anisotropic phenomena). The influence of deviations from planarity, concerning either MN2Cl2 chromophores or azine ring systems, revealed by the known X-ray structures of [Pd(bquin)Cl2] and [Pt(bquin)Cl2], is discussed in respect to 1H NMR spectra. 15N coordination shifts (Delta15Ncoord=delta15Ncomplex-delta15Nligand) of ca. 78-100 ppm (to lower frequency) are attributed mainly to the decrease of the absolute value of paramagnetic contribution in the relevant 15N shielding constants, this phenomenon being noticeably dependent on the type of a platinide metal and coordination sphere geometry. The absolute magnitude of Delta15Ncoord parameter increased by ca 15 ppm upon Pd(II)-->Pt(II) replacement but decreased by ca. 15 ppm following trans-->cis transition. Experimental 1H, 13C, 15N NMR chemical shifts are compared to those quantum-chemically calculated by B3LYP/LanL2DZ+6-31G**//B3LYP/LanL2DZ+6-31G*, both in vacuo and in CHCl3 or DMF solution.     

Multinuclear 1H, 13C and 15N NMR study of some substituted 2-amino-4-nitropyridines and their N-oxides

1H, 13C and 15N NMR chemical shift assignments based on pulsed field gradient selected PFG 1H,X (X = 15C and 15N) HMQC and HMBC experiments are reported for three 4-nitropyridine N-oxides and four 4-nitropyridines. It was found that an ortho effect of a methyl group inhibits the deshielding effect of the 4-nitro group and that this effect and the so-called back donation is influenced by electronegativity and position of substituents in the multisubstituted pyridine N-oxides. The shielding effect of N-oxide group is most pronounced in the 15N NMR chemical shifts of the studied compounds. This effect is further modified by methylamino, methylnitramino, 5- or 3-methyl and 4-nitro groups. Among them the 4-nitro group exerts the highest influence on the shielding effect of the N-oxide functionality. Experimental 1H, 13C and 15N NMR chemical shifts and GIAO/DFT theoretical calculations are consistent with each other and supported by the reactivity on nucleophilic substitution, the UV spectral and the dipole moment data.     

Carbon-13 NMR spectra of DDT,its analogues and related compounds

Carbon-13 NMR spectra of mono- and disubstituted aromatic compounds including DDT, its analogues, homologues, derivatives and certain model compounds have been studied. The Savitsky scheme of carbon chemical shifts in disubstituted benzenes is applicable to these compounds. The data obtained show that in mono- and disubstituted aromatic compounds containing two different substituents in the α- and β-positions of the side chain, the substituted ring carbon atom shifts follow the additivity rule and can be calculated from substituent increments. Mutual effects of substituents in the ring and in the side chains are analysed. The chlorine atoms in α-position to the phenyl ring give rise to an additive α-effect of about 25 ppm, as in perchloroalkanes. The influence of a β-chlorine atom in the side chain on the substituted carbon atom in the ring is, however, only 3 ppm as against the usual value of about 10 ppm for the β-effect in alkyl chains. Moreover, the first β-chlorine substituent has no noticeable influence on the substituted ring carbon chemical shift: the effect of 3 ppm is transferred to the para-carbon atom almost without attenuation. The ring substituted carbon atom signal shifts caused by the γ-effect of chlorine in the side chain are similar to those observed in aliphatic chains. The ortho-chlorine substituents shift the side chain α-carbon atom signal by 3.6-5.2 ppm to high field compared to para-chlorophenyl compounds. This is similar to the chlorine γ-effect in aliphatic chains.     

Experimental and quantum-chemical studies of 1H, 13C and 15N NMR coordination shifts in Pd(II) and Pt(II) chloride complexes with methyl and phenyl derivatives of 2,2'-bipyridine and 1,10-phenanthroline

1H, 13C and 15N NMR studies of platinide(II) (M=Pd, Pt) chloride complexes with methyl and phenyl derivatives of 2,2'-bipyridine and 1,10-phenanthroline [LL=4,4'-dimethyl-2,2'-bipyridine (dmbpy); 4,4'-diphenyl-2,2'-bipyridine (dpbpy); 4,7-dimethyl-1,10-phenanthroline (dmphen); 4,7-diphenyl-1,10-phenanthroline (dpphen)] having a general [M(LL)Cl2] formula were performed and the respective chemical shifts (delta1H, delta13C, delta15N) reported. 1H high-frequency coordination shifts (Delta1Hcoord=delta1Hcomplex-delta1Hligand) were discussed in relation to the changes of diamagnetic contribution in the relevant 1H shielding constants. The comparison to literature data for similar [M(LL)(XX)], [M(LL)X2] and [M(LL)XY] coordination or organometallic compounds containing various auxiliary ligands revealed a large dependence of delta1H parameters on inductive and anisotropic effects. 15N low-frequency coordination shifts (Delta15Ncoord=delta 15Ncomplex-delta15Nligand) of ca 88-96 ppm for M=Pd and ca 103-111 ppm for M=Pt were attributed to both the decrease of the absolute value of paramagnetic contribution and the increase of the diamagnetic term in the expression for 15N shielding constants. The absolute magnitude of Delta15Ncoord parameter increased by ca 15 ppm upon Pd(II)-->Pt(II) transition and by ca 6-7 ppm following dmbpy-->dmphen or dpbpy-->dpphen ligand replacement; variations between analogous complexes containing methyl and phenyl ligands (dmbpy vs dpbpy; dmphen vs dpphen) did not exceed+/-1.5 ppm. Experimental 1H, 13C, 15N NMR chemical shifts were compared to those quantum-chemically calculated by B3LYP/LanL2DZ+6-31G**//B3LYP/LanL2DZ+6-31G*, both in vacuo and in DMSO or DMF solution.     

Analysis of the β-methylene carbon-13 NMR chemical shifts: from vinylidene chloride copolymers to a general analysis of polymers

Analysis of the carbon-13 NMR chemical shifts of β-methylene of vinylidene chloride copolymers has been done. The analysis, based on the empirical additivity rules, proposes chemical shift additive parameters for the monomer units in vinylidene chloride copolymers. Genetic algorithm has been applied for the optimization of additive parameters. To simplify and generalize the analysis, common functional groups present in the pendant groups; Cl, COOCH₃, CH₃, OCOCH₃, CN, CONH₂, C₆H₅ and COOH substituents were modeled and their additive effects were optimized. The additive parameters enabled to predict the carbon-13 NMR chemical shifts of β-methylene of homopolymers and copolymers at tetrad level of compositional sensitivity.     

1H NMR spectra part 31: 1H chemical shifts of amides in DMSO solvent

The ¹H chemical shifts of 48 amides in DMSO solvent are assigned and presented. The solvent shifts Δδ (DMSO‐CDCl₃) are large (1–2 ppm) for the NH protons but smaller and negative (?0.1 to ?0.2 ppm) for close range protons. A selection of the observed solvent shifts is compared with calculated shifts from the present model and from GIAO calculations. Those for the NH protons agree with both calculations, but other solvent shifts such as Δδ(CHO) are not well reproduced by the GIAO calculations. The ¹H chemical shifts of the amides in DMSO were analysed using a functional approach for near ( ≤ 3 bonds removed) protons and the electric field, magnetic anisotropy and steric effect of the amide group for more distant protons. The chemical shifts of the NH protons of acetanilide and benzamide vary linearly with the π density on the αN and βC atoms, respectively. The C=O anisotropy and steric effect are in general little changed from the values in CDCl₃. The effects of substituents F, Cl, Me on the NH proton shifts are reproduced. The electric field coefficient for the protons in DMSO is 90% of that in CDCl₃. There is no steric effect of the C=O oxygen on the NH proton in an NH…O=C hydrogen bond. The observed deshielding is due to the electric field effect. The calculated chemical shifts agree well with the observed shifts (RMS error of 0.106 ppm for the data set of 257 entries). Copyright © 2014 John Wiley & Sons, Ltd.     

1H, 13C and 15N NMR studies on adducts formation of rhodium(II) tetraacylates with some azoles in CDCl3 solution

Adduct formations of rhodium(II) tetraacetate and tetratrifluoroacetate with some 1H-imidazoles, oxazoles, thiazoles, 1H-pyrazoles and isoxazole have been investigated by the use of 1H, 13C, 15N NMR and electronic absorption spectroscopy (VIS) in the visible range. Azoles tend to form axial adducts containing rhodium(II) tetraacylates bonded via nitrogen atom. Bulky substituents close to the nitrogen atom prevent the Rh--N bond formation, and in several cases switch over the binding site to the oxygen or sulphur atoms. The (15)N adduct formation shift Deltadelta(15N) (Deltadelta = delta(adduct) - delta(ligand)) varied from ca - 40 to - 70 ppm for the nitrogen atom involved in complexation, and of a few parts per million only, from ca - 6 to 3 ppm, for the non-bonded nitrogen atom within the same molecule. The Deltadelta(1H) values do not exceed one ppm; Deltadelta(13C) ranges from - 1 to 6 ppm. Various complexation modes have been proved by electronic absorption spectroscopy in the visible region (VIS). For comparison purposes, some adducts of pyridine, thiophene and furan derivatives have been measured as well. The experimental findings were compared with calculated chemical shifts, obtained by means of DFT B3LYP method, using 6-311 + G(2d,p), 6-31(d)/LanL2DZ and 6-311G(d,p) basis set.     

Comparative analysis of 13C shielding constants stereospecificity in the silicon and germanium derivatives of acetylenic aldehyde and ketone oximes based on the 13C NMR spectroscopy and GIAO calculations

In the acetylenic aldehyde oximes with substituents containing silicon and germanium, the ¹³C NMR signal of the C‐2 carbon of triple bond is shifted by 3.5 ppm to lower frequency and that of the C‐3 carbon is moved by 7 ppm to higher frequency on going from E to Z isomer. A greater low‐frequency effect of 5.5 ppm on the C‐2 carbon signal and a greater high‐frequency effect of 11 ppm on the C‐3 carbon signal are observed in the analogous acetylenic ketone oximes. The carbon chemical shift of the C?N bond is larger by 4 ppm in E isomer relative to Z isomer for the aldehyde and ketone oximes. The ²⁹Si chemical shifts in the silicon containing acetylenic aldehyde and ketone oximes are almost the same for the diverse isomers. The trends in changes of the measured chemical shifts are well reproduced by the gauge‐including atomic orbital (GIAO) calculations of the ¹³C and ²⁹Si shielding constants. Copyright © 2009 John Wiley & Sons, Ltd.     

Carbon-13 NMR studies of quinolines and isoquinolines. II. Chlorine–nitrogen interactions and N-oxide effects

Carbon-13 chemical shift assignments are reported for four chloroquinolines, six chloroisoquinolines, one dichloroquinoline, four dichloroisoquinolines, four methylchloroquinolines, two methylchloroisoquinolines, quinoline N-oxide, isoquinoline N-oxide, five methylquinoline N-oxides, two methylisoquinoline N-oxides and three chloroisoquinoline N-oxides. Chlorine substituent chemical shift (SCS) effects are reported for the alpha, ortho, meta, para and peri positions. Consistent patterns are observed for the para and peri positions, a vinylogous ortho pattern is reported and the additivity of these SCS effects is demonstrated. Alpha SCS effects vary widely from 1.1 ppm upfield in 1-chloroisoquinoline to 6.7 ppm downfield in 4-chloroquinoline. These results, together with those in the literature, permit the definition of steric and nitrogen lone-pair contributions which modify the ‘normal’ chlorine SCS effect, and these modifying contributions are shown to be roughly additive. Large (6–16 ppm) upfield shifts are observed for the carbons ortho and para to the N-oxide group. The individual magnitudes of these shifts and their sum are constant and the effects are additive in substituted systems. A 9.5 ppm upfield shift is also observed for C-8 in quinoline N-oxides which is attributed to a space–charge interaction. Substituent chemical shift (SCS) effects for the chloro and methyl groups and the chemical shifts of the methyl carbons are essentially the same in the N-oxides as in the parent heterocycles and are additive, except for those molecules where the substituent is adjacent to the N-oxide moiety, in which cases substantial interactions are observed.     

The impact of the pi-electron conjugation on (15)N, (13)C and (1)H NMR chemical shifts in push-pull benzothiazolium salts. Experimental and theoretical study

The (15)N as well as (13)C and (1)H chemical shifts of eight push-pull benzothiazolium iodides with various pi-conjugated chains between dimethylamino group and benzothiazolium moiety have been determined by NMR spectroscopy at the natural-abundance level of all nuclei in DMSO-d(6) solution. In general, the quaternary benzothiazolium nitrogen is more shielded [delta((15)N-3) vary between - 241.3 and - 201.9 ppm] with respect to parent 3-methylbenzothiazolium iodide [delta((15)N-3) = - 183.8 ppm], depending on the length and constitution of the pi-conjugated bridge. A larger variation in (15)N chemical shifts is observed on dimethylamino nitrogen, which covers the range of - 323.3 to - 257.2 ppm. The effect of pi-conjugation degree has a less pronounced influence on (13)C and (1)H chemical shifts. Experimental data are interpreted by means of density functional theory (DFT) calculations. Reasonable agreement between theoretical and experimental (15)N NMR chemical shifts was found, particularly when performing calculations with hybrid exchange-correlation functionals. A better accord with experiment is achieved by utilizing a polarizable continuum model (PCM) along with an explicit treatment of hydrogen-bonding between the solute and the water present in dimethylsulfoxide (DMSO). Finally, (13)C and (1)H NMR spectra were computed and analysed in order to compare them with available experimental data.     

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.     

15N NMR substituent effects in pyridines and pyrimidines

¹⁵N chemical shifts of 32 substituted pyridines and 19 substituted pyrimidines, together with additional data from the literature, are used to evalute substituent increments, A_i and A_ik, in the respective series. Differential chemical shifts, Δδ(N), correlate with corresponding Δδ(C) values whereby, on the ppm scale, nitrogen shifts are approximately three times more sensitive towards substituents than carbon shifts. The ¹⁵N increments have proven additive and useful for assignment purposes.