Carbon-13 nuclear magnetic resonance studies of creatine,creatinine and some of their analogs

Creatine (N-methyl-N-amidinoglycine), creatinine (1-methyl-2-aminoimidazolin-4-one) and a series of 38 of their close structural analogs have been examined using natural abundance ¹³C NMR spectroscopy at 25.16 MHz. Both proton-coupled and proton noise-decoupled spectra were recorded. Unequivocal assignments of the carbon resonances could be made in the vast majority of cases. Both ¹³C NMR chemical shifts and ¹J(CH) values can be used to characterize and to differentiate readily between analogs of creatine and analogs of creatinine. For example, the ¹J(CH) coupling constants for the α-carbons of the acyclic creatine analogs were all in the 140–142 Hz range, whereas the corresponding coupling constants for the related, cyclized creatinine analogs were all in the 150–152 Hz range.     

Tetraphenylporphyrin molecules containing heteroatoms other than nitrogen: 8—A carbon-13 NMR study

The ¹³C NMR spectra of new hetero-substituted tetraphenylporphyrin (TPP) molecules have been studied. It was found that most of the carbon chemical shifts are similar to those found in TPP. The similar chemical shifts of the different β-carbons in S₂TPP and in Se₂TPP free bases and, moreover, the considerable downfield shift of the α-carbons of the S(Se)-rings on protonation are in agreement with the previously suggested theory of inner and outer aromaticity in these porphyrins.     

13C NMR spectra of alkyl- and phenylpyrazines and their N-oxides

The ¹³C chemical shifts of 37 pyrazines, including their N-oxides, are reported. Substituent effects of methyl, phenyl and N-oxide groups on the chemical shifts were examined. To comprehend these effects, the chemical shifts were compared with charge densities calculated by the CNDO/2 method and a good correlation was obtained. ¹³C, ¹H coupling constants of some pyrazines were also determined and assigned. These data enable us to assign the ¹³C NMR spectra of substituted pyrazines and to understand the effects of N-oxidation on the pyrazine nuclei.     

13C NMR studies of reduced porphyrin compounds. Aromatic delocalization pathways

¹³C NMR spectra of ms-tetraphenylchlorins, new aminoalkyl- and hydroxy-pyrroline substituted ms-tetra-phenylchlorins, and ms-tetraphenylisobacteriochlorins are presented and discussed. Significant changes in the chemical shifts of the α-pyrrole, α-pyrroline and meso skeletal carbons are found in chlorins and isobacteriochlorins in comparison to porphyrins. In contrast, the chemical shifts of the β-pyrrole carbons are almost unaffected by the structural modifications in chlorin and isobacteriochlorin. The chemical shifts of the α-pyrrole carbons in the various chlorins and isobacteriochlorins are strongly affected by the substitutents of the pyrroline ring, or by the introduction of an additional pyrroline ring in isobacteriochlorins. The results show that most of the electron density is concentrated in the unreduced part of the molecule, i.e. in the pyrrole rings and, especially, on the α-pyrrole carbons and is transferred or removed through the aromatic pathway by substituents on the pyrroline ring. These observations are supporting evidence that the α-pyrrole, α-pyrroline and meso-carbons are in the aromatic pathway and favour the proposal of a 16 atom dianion as the preferred delocalization pathway in chlorins and isobacteriochlorins.     

Enantiomeric NMR signal separation mechanism and prediction of separation behavior for a praseodymium (III) complex with (S,S)-ethylenediamine-N,N-disuccinate

Because choice of chiral nuclear magnetic resonance (NMR) shift reagents and concentration conditions have been made empirically by trials and errors for chiral NMR analyses, the prediction of NMR signal separation behavior is an urgent issue. In this study, the separation of enantiomeric and enantiotopic ¹H and ¹³C NMR signals for α-amino acids and tartaric acid was performed by using the praseodymium(III) complex with (S,S)-ethylenediamine-N,N′-disuccinate ((S,S)-EDDS). All the present D-amino acids exhibited larger downfield shift of their α-protons and α-carbons compared with those for the corresponding L-amino acids in common. This regularity is applicable to absolute configurational assignment and determination of optical purity of amino acids. The chemical shifts of β-protons of d - and l -alanine fully bound with the Pr(III) ((S,S)-EDDS) complex (δ_bs) and the adduct formation constants of both enantiomers (Ks) were obtained by dependences of the observed downfield shifts of the β-protons on the total concentrations of the respective enantiomers in the presence of a constant concentration of the Pr(III) complex. The difference in the K values was found to be predominant determining factor for the enantiomeric signal separation. The chemical shifts of both enantiomers (δs) and the enantiomeric signal separations (Δδs) under given conditions could be calculated from the δ_b and K values. Furthermore, prediction of the signal separation behavior was enabled by using the calculated δ values and the signal broadening obtained by dependences of the half-height widths of the observed signals on the bound/free substrate concentration ratios for the respective enantiomers.     

13C, 14N, 15N and 17O NMR spectra of nitropyrroles and nitroimidazoles

Carbon, nitrogen and oxygen NMR spectra of some nitro derivatives of pyrrole and imidazole have been investigated. The ¹³C chemical shifts of para-carbons and the ¹⁷O chemical shifts of the nitro group correlate qualitatively with the electron densities on these carbon and oxygen atoms, which in turn depend upon the degree of conjugation of the nitro groups with the heterocyclic ring. Conjugation of several nitro groups with the benzene ring is in most cases not impaired by mutual interactions and the ¹³C shifts show good additivity. Such additivity is much worse in pyrrole and imidazole derivatives. Taken together with the diamagnetic nature of these deviations from additivity, this leads to a possible conclusion about the less pronounced conjugation of the nitro groups with the heterocyclic ring in heterocyclic dinitro derivatives.     

13C NMR studies of conformational isomerism in thioureas: Signal assignments via chemical shift and population trends

The 22.63 MHz ¹³C NMR spectra of a series of alkylated thioureas are reported. Characteristic Z and E spectral regions were found for the ¹³C ? S resonances. The two regions were generally found to be non-overlapping for the series, with the region of the Z, Z resonances occurring more downfield than those of either the Z, E or E, Z conformers in the cases of 1,3-disubstitution. The Z, Z configuration became favored and the relative chemical shift difference (Rδ) increased linearly with increasing substituent size. At 217 K, hindered internal rotation caused a multiplicity of resonances which were normally single peaks in the broad band ¹H decoupled 62.86 MHz ¹³C spectrum of CH₃NHCSNH(CH₂)₂NHCSNHCH₃ (2MTE) at room temperature. The trends in chemical shifts and populations were employed to assign tentatively the resonances of five of the six possible configurational isomers contributing to the 2MTE spectra at 217 K. The isomer populations are given. The ¹³C NMR spectra reported here led to signal assignments of Z and E isomers which supported prior ¹H NMR results and contradicted more recent results of another ¹³C NMR study of N-methylthiourea. The major peak of the exchange doublet occurs at relatively high field strengths in both methanol-d₅.     

13C and 1H NMR investigation of the structure of N″-sulphonyl-N-alkylideneformamidrazones

The ¹³C and ¹H NMR spectra of N″-sulphonyl-N-alkylideneformamidrazones have been recorded and the chemical shifts assigned. The tautomeric structure proved to be an N²- alkylidenehydrazide sulphonylimide. The barrier to rotation around the CN¹ bond was estimated from variable from temperature ¹H NMR measurements, and the Z/E ratio and its solvent dependence was investigated.     

Carbon-13 chemical shifts of α,β-unsaturated acids

Carbon-13 spectra of 59 α,β-unsaturated carboxylic acids have been measured. Large differential shieldings of ethylenic carbons in the cis and trans isomers of acrylic acid derivatives were found (altogether 15 isomeric Z- and E-pairs of acids were investigated). The origin of differential shieldings is complex and both molecular ground states as well as changes in excited states appear to be involved. All measured ¹³C chemical shifts can be described by additive parameters that provide a straightforward new technique by which structural assignments can be made for a wide variety of isomeric mono-, di- and tri- substituted α,β-unsaturated acids.     

Electronic effects in the cyclopentadienyl ring. The 13C NMR spectraof monosubstituted ferrocenes

The chemical shifts of C(2,5) and C(3,4) carbons in the ¹³C NMR spectra of monosubstituted ferrocenes have been assigned using deuterium labelling. An analogy is observed between the shielding of C(2,5) and C(3,4) carbons of ferrocene derivatives and ortho- and para-carbons of benzene derivatives withthe same substituents. Electron-density distribution in the cyclopentadienyl ring is discussed on the basis of ¹³C NMR data.     

Spectroscopie RMN du Carbone-13 de Thiocétones Aliphatiques: Propanethione et Dérivés,Thiocétones Bicycliques et α Cyclopropaniques

Carbon-13 NMR spectra of various aliphatic ketones and thioketones were determined and interpreted. As shown by the relation between ¹³C chemical shifts in C=A groups, the C=S is more sensitive to the substituents than the C=O group. Conjugative effects are more pronounced in α-cyclopropyl thioketones than in α-cyclopropyl ketones.     

X-ray photoelectron spectra and structure of 2-(2-phenylhydrazono) acetoacetanilide

2-(2-Phenylhydrazono)acetoacetanilide, itsN-methyl derivatives, and model compounds were studied by X-ray photoelectron spectroscopy. The chemical shifts were obtained from the¹³C NMR spectra. A correlation between the calculated charges, the binding energies on N atoms, and the¹³C NMR chemical shifts was found. The analysis of the XPS data and the¹³C NMR chemical shifts led to the conclusion that crystalline 2-(2-phenylhydrazono)acetoacetanilide exists mainly in the oxo hydrazone form. Translated fromIzvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 488–491, March, 1999.     

Substituent effects on 13C and 1H chemical shifts in 3-benzylidene-2,4-pentanediones

Substituent effects on the ¹³C and ¹H chemical shifts have been studied for derivatives of 3-benzylidene-2, 4-pentanedione. A significant correlation has been found between chemical shifts of the Z carbonyl group (C-2) and Hammett constants, while no correlation has been found for the E carbonyl group (C-4). Attempts have been made to determine the structural factors which influence these effects. The conformation of 3-benzylidene-2, 4-pentanediones has been determined by ¹³C and ¹H NMR spectroscopy.     

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.     

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.     

Downfield γ-gauche and γ-antiperiplanar effects on 13C NMR chemical shifts exerted by thiophene sulphur

The γ-effects of sulphur on ¹³C NMR chemical shifts have been measured in a series of steroidal compounds containing the thiophene ring in different configurations with respect to the rest of the molecule. The data constitute the first example of downfield effects exerted by sulphur on both gauche and antiperiplanar γ-carbons. The γ-gauche effect of sulphur amounts to 1.6–1.8 ppm, the γ-antiperiplanar effect from practically zero to almost 1 ppm.     

A NEW SYSTEM EXHIBITING A HIGH BARRIER TO ROTATION ABOUT THE P—N BOND. SYNTHESES AND SPECTRAL STUDIES OF 1,3,2-DIAZAPHOSPHETIDIN-4-ONE DERIVATIVES

Abstract

1,3,2-Diazaphosphetidin-4-one derivatives were synthesized. Their ¹H NMR signals at ambient temperature displaed a broad doublet which eventually coalesced before becoming sharp upon warming, and the ¹³C NMR spectra also showed that the α-and β-carbons of the dialkylamino group were non-equivalent. The phenomena were ascribed to restricted rotation about the exocyclic P—N bond.     

Substituent effects on 13C NMR chemical shifts in the saturated framework of primary aliphatic derivatives

A general equation describing the effect of substituents on α-carbons in a saturated framework was developed from ¹³C chemical shifts obtained under uniform conditions for selected aliphatic compounds. Experimental correlations for β- and γ-carbons and a discussion of the results are presented.     

Carbon-13 NMR and conformational analysis of meso- and dl-α,α′-disubstituted succinic acids

meso-and dl-Diastereomers of a number of α,α′-disubstituted succinic acids have been shown to give different ¹³C NMR chemical shifts. The results can be satisfactorily explained on the basis of their conformational analyses. A discussion of the observed chemical shifts is presented, and the preferred conformation for each of several compounds is predicted on the basis of these chemical shifts.     

13C-NMR-Spektren von Cyclopropenen und Benzocyclopropenen

The substituent parameters of methyl-, halogen-, methoxycarbonyl- and phenyl-substituted cyclopropenes as well as of cyclopropenone and diphenylcyclopropenone are determined from the ¹³C chemical shifts. The influence of the carbonyl group on the chemical shifts and charge densities is studied in the cyclopropenones. The interaction between the cyclopropene nucleus and the annulated benzene ring in benzocyclopropenes is evaluated with the aid of the ¹³C NMR spectra of di- and tetraphenyl-substituted benzocyclopropene derivatives and of dimethyl 1H-cyclopropa[a]naphthalene-1,1-dicarboxylate. The J values are shown to be better indicators of structural changes than the δ values. α-Effects of substituents give a good correlation with Hammett σ₁-values.