Temperature effects on 13C n.m.r. chemical shifts of normal alkanes and some line r and branched 1-alkenes

¹³C n.m.r. chemical shifts of a number of 1,1-disubstituted ethylenes are presented. Moreover, effects of changing temperatures on the ¹³C n.m.r. chemical shifts of some of these compounds as well as of three normal alkanes are given. These variations in chemical shifts are attributed to varying amounts of sterically induced shifts in the different conformational equilibria. In addition to the well-known 1,4 interaction between two alkyl groups shielding effects on the carbon atoms of the connecting bonds are also proposed. No definite explanation of this effect is presented at this time. It is further shown that no simple correlations exist between ¹³C n.m.r. chemical shifts and calculated total charge densities at this level. Instead, the experimental results in 1-alkenes are rationalized by assuming a linear dependence of the ¹³C n.m.r. chemical shifts of C-1 and C-2 via rehybridizations on changes in bond angles for small skeletal deformations caused by steric interactions. These changes in geometries, as well as conformational energies in three 1-alkenes, were calculated by means of VFF calculations. Finally. upfield shifts for both C-2 and C-4 are proposed for those conformations of 1-alkenes in which the C-3? C-4 group interacts with the p_z-orbital of C-2.     

1H AND 13C NMR SPECTRA OF 1-DEOXY-1-THIOGLYCOPYRANOSIDES

Abstract

In the absence of previous systematic investigations, we have embarked on the study of the NMR spectra of thioglycosides, as we needed structural information in connection with our work on the spectroscopic properties of these compounds. In this sommunication, data will be presented on alkyl α - and β-thiogluco- and -thiogalactopyranosides and some related compounds, including certain natural products like lincomycin, sinigrin, and glucocapparin. The ¹H spectra of the strongly coupled carbohydrate portion can readily be analyzed at 270 MHz in the case of the thiogalactosides, whereas the spectrum of the thioglucose moiety in, e.g., thioglucose sodium salt, remains a system of higher order even at 360 MHz, giving rise to multiple lines and virtual coupling. The assignment of the ¹³ spectra proceeded basically via selective or via frequency dependant off-resonance heteronuclear double resonance experiments at 68 MHz; the C-H coupling pattern (triplet) directly reveals the position of C-(6). Application of the increment method of the ¹³C chemical shift in connection with the thioalkyl grouping presented no complications. Tetraacetylation of the thioglycosides shifts the ring ¹³C resonances in a systematic manner and is, therefore, an additional aid. All the compounds investigated adopt the ⁴C₁ conformation; in the α-series, ³J(H-1/H-2) = ca. 5.5 Hz, i.e., relatively large. Long range ¹³C- ¹H coupling constants were measured in a few cases only. Values of ¹J (¹³C- ¹H) were also obtained from satellite lines in the appropriate high-field ¹H spectra. From the spectra of the fully or partly analyzed compounds rules can be deduced that are especially helpful in the examination of ¹³C spectra of other thioglycosides, employing, e.g., chemical shift data, coupling constants, and T₁ data.     

The assignment of the 1H and the 13C NMR chemical shifts of N-phenyl-2,4-dimethylbuta-1,3-diene-1,4-sultam

The assignment of the signals in the ¹³C and ¹H NMR spectra of N-phenyl-2,4-dimethylbuta-1,3-diene-1,4-sultam is difficult for the signal pairs C-2 and C-4, C-1 and C-3, (C-1)? H, (C-2)? CH₃ and (C-4)? CH₃. The ¹³C NMR spectrum recorded under gated decoupling conditions provide long-range couplings which make possible an unambiguous assignment of the ¹³C NMR signal pairs. Application of the ¹H CW off-resonance decoupling technique in recording the ¹³C NMR spectra enables the assignment information from the ¹³C NMR spectrum to be transferred to the ¹H NMR spectrum.     

13C-13C spin-spin coupling constants in six-membered ring azaaromatic compounds

The ¹³C-{¹H} NMR spectra of monomethyl substituted diazines, protonated at the picoline and 2-methylopyrimidine nitrogen atoms, have been analyzed, along with that of pyridine N-oxide and its 2-methyl derivatives protonated at the oxygen atom. Direct and vicinal ¹³C-¹³C spin-spin coupling constants (SSCC) have been measured. It was found that the ¹³C-¹³C SSCC in diazines follow additivity rules which are based on consideration of the number and mutual orientation or distribution of nitrogen atoms in the ring. It has also been demonstrated that increased direct ¹J_CC values involving methyl group carbon atoms in -positions to nitrogen atoms in the aromatic ring are due to effects associated with unshared electron pairs.Translated from Khimiya Geterotsiklieheskikh Soedinenii, No. 9, pp. 1243–1250, September, 1988.     

Carbon-13 NMR spectra of a series of para-substituted N,N-dimethylbenzamides. Comparisons of linear free energy relationships for carbon-13 and nitrogen-15 chemical shifts and rotation barriers

All carbon-13 chemical shifts for 11 para-substituted N,N-dimethylbenzamides in 1 mole % chloroform solution are reported, with assignments based upon double resonance experiments, analogy to chemical shifts of benzamide, and self-consistency between experimental and calculated values using recognized substituent parameters. In contrast to earlier reports, the aryl carbon chemical shift assignments for N,N-dimethylbenzamide are C-2, 127.0; C-3, 128.7; C-4, 129.4, and for p-chloro-N,N-dimethylbenzamide are C-1, 134.6; C-4, 135.5 ppm, relative to internal TMS. Good Hammett correlations (σ_p) are reported for ¹³C chemical shifts of C-1 (σ = 11.9 ppm) and even for the carbonyl group (σ = ?2.3 ppm) but are markedly improved if correlated with σ_p+ (σ = 9.5 ppm) and Dewar's F (σ = ?1.9 ppm), respectively. Excellent Swain–Lupton F and R correlations were found for some of the ¹³C chemical shifts and yielded values for percent resonance contributions to transmission of substituent effects as follows, C-1, 75 ± 4%; C-2, 51 ± 3%; C?O, 31±2%. These are compared to similar values calculated from the C?O of benzoic acids of 34±10%, and from the nitrogen-15 chemical shifts of benzamides of 56±2%. Correlations of these ¹³C δ values and ¹⁵N δ values with rotation barriers (ΔG) for N,N-dimethylbenzamides were examined, and it was found that while C?O δ values correlated only poorly the C-1 δ values correlated very well, but the best correlation was for ¹⁵N δ values of benzamides. It is suggested that Δ G and δ ¹⁵N are intrinsically related due to their numerical correlation, and the close similarity in percent resonance contribution of substituent influence on these parameters.     

Aufkl?rung der 1H- und 13C-NMR-spektren sowie der kristallstruktur unges?ttigter glycosylphosphonate und konformationsberechnungen an modellen1

By application of a modified LAOCN-3 program a complete elucidation of the ¹H NMR spectra of 2,3-unsaturated glycosyl phosphonates 1–5 could be achieved. The exactly determined ⁿJ(H, H) and novel ⁿJ(C, P) coupling constants are discussed, and permit a conclusive deduction of the conformations. The ¹³C NMR spectra of 1 to 6 can be fully interpreted. By a close inspection of chemical shifts as well as ¹J(C-H) and ⁿJ(C, P) coupling constants the conformational assignment is supported. For all the derivatives the correlations ¹J(C-1,H_e)>¹J(C-1, H_a) and ¹J(C-1, P_e) >¹J(C-1, P_a) can be used for the assignment of anomers. The crystal structure of 1 is in accordance with this assignment of anomers and displays an unexpected conformation. Calculations by MINDO-3 in resembling model compounds serve to elucidate such conformative effects.     

Carbon-carbon coupling in [3-13C1]tryptophan

Carbon-carbon coupling constants have been observed in [90% 3-¹³C₁]tryptophan and used to assign the ¹³C resonances of the indole ring. The results support a reassignment of C-5 and C-6 recently suggested on the basis of the reassigment of the corresponding resonances in indole. Coupling constants are compared with theoretical values obtained using a finite perturbation theory Blizzard-Santry program, and excellent agreement is obtained for the ¹J(CC) values. The calculations predict that the Fermi contact contribution is dominant for all ⁿJ(CC) couplings to C-3.     

13C- and 1H-NMR studies of N-substituted 1,2,4-triazoles. Relative basicities of triazolic rings

Summary ¹³C- and ¹H-NMR spectra of N-substituted-1,2,4-triazoles were conjointly studied. A linear relationship (C-3) vs. _m was obtained allowing use of ¹³C-NMR to estimate the relative basicities of the heterocyclic ring of 1,2,4-triazoles substituted on N-1.

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¹³C- und ¹H-NMR-Untersuchungen von N-substituierten 1,2,4-Triazolen. Relative Basizitäten von Triazolringen

     

Characterization of organic substrates bound to cross-linked polystyrenes by 13C NMR spectroscopy

The ¹³C NMR spectra of a wide variety of organic substrates bound to 2% cross-linked polystyrenes may be obtained routinely, provided the resins can be sufficiently swollen. The ¹³C chemical shifts of polymer-bound trityl alcohol, polymer-bound monotrityl ethers of the symmertrical diols HO (CH₂)_nOH (n=2, 4, 6, 7, 9 and 10), and some related intermediates in the solid phase synthesis of insect pheromones are presented. ¹³C shift additivity correlations, differing little from those in free trityl ethers, are drawn.     

Carbon-13 nuclear magnetic resonance studies of anthraquinones. Part III—correlation of substituent effects for 2-substituted anthraquinones

The ¹³C chemical shifts of 2-substituted and 2,6-disubstituted anthraquinones have been determined and assigned. The C-1, 2, 3, 4, 13 and C-14 chemical shifts of 2-substituted anthraquinones are correlated with the chemical shifts of monosubstituted benzenes. A three-parameter correlation with Swain and Lupton's ? and ? parameters and Schaefer's Q parameter provides relationships for the prediction of all chemical shifts of 2-substituted anthraquinones from the substituent parameters. Q values for the SCH₃, OCOCH₃, C₂H₅ and C(CH₃)₃ groups are proposed. The two types of correlations are compared for predicting chemical shifts.     

Carbon-13 NMR spectra of a series of para-substituted phenyl isothiocyanates. Linear free energy relationships for carbon-13 substituent chemical shifts

Carbon-13 chemical shifts are reported for 16 para-substituted phenyl isothiocyanates measured at 1 and 10 mol % in chloroform-d solution. Data for the ? N?C?S group were not obtained at 1 mol %, but concentration effects for the other resonances were negligible. Hammett, dual substituent parameter (DSP) and DSP-nonlinear resonance (DSP-NLR) analyses were used to evaluate substituent effects on the substituent chemical shifts (SCS) for the ipso-carbon (C-1), C-2, and the ? N?C?S carbon atoms. A good Hammett correlation was observed for C-1 (ν_p⁺ = 8.1 ppm, r = 0.98 at 1 mol %) but was improved for the higher order correlations with the following results, DSP:ρ _I = 5.4, ρ_R° = 22.2, r = 0.998; DSP-NLR: ρ_I = 5.6, ρ_R° = 20.5, ? = ?0.22, r = 0.999. The 10 mol % data were very similar except the value of ? was ?0.26 and confirms the phenyl-bonded ? N?C?S moiety as a mild electron acceptor substituent. Hammett correlations were unsuccessful for the C-2 data, but fairly good results were obtained from the higher order analyses. For the 1 mol % data, DSP: ν_I = 1.6, ν_R° = ?2.0, r = 0.976; DSP-NLR: ν_I = 1.8, ν_R° = ?2.6, ? = 1.1, r = 0.982. Excellent correlations were obtained for the 10 mol % ? N?C?S carbon data. Hammett: ν_p° = 6.2, r = 0.997; DSP: ν_I = 5.9, ν_R° = 7.0, r = 0.997; DSP-NLR: ν_I = 5.8, ν_R° = 7.6, ? = 0.25, r = 0.997. The positive ν values in these three correlations contrast the negative values usually observed for carbonyl and thiocarbonyl carbons, and more closely parallel results previously reported for the β-carbon of styrenes and benzylidene anilines with para-substituents in the aniline ring.     

Convergent syntheses of carbon-13 labeled midazolam and 1′-hydroxymidazolam

For the purpose of drug interaction studies, the stable-isotope labeled [¹³C₃]midazolam and its metabolite, 1′-hydroxy-[¹³C₃]midazolam were synthesized in four and five steps in overall yields of 25.5% and 14.2%, from 7-chloro-5-(2-fluorophenyl)-2-(N-nitrosomethylamino)-3H-1,4-benzodiazepine, respectively, by a convergent synthesis, in which a key imidazoline ring formation was achieved by the facile reaction of [¹³C]2-aminomethyl-7-chloro-2,3-dihydro-5-(2-fluorophenyl)-1H-1,4-benzodiazepine with varying ethyl imidate hydrochlorides. The scrambling of C-3 and C-4 labeling in intermediate diamine, and consequently in the final products, as well as the formation of a Δ^4,5 isomer of 1′-hydroxy-[¹³C₃]midazolam was observed and explained.     

1H and13C NMR spectra of biologically active compounds. III. Diastereomers of (±)-7-thia- and 13-thia-16-aryloxy analogs of 11-deoxyprostaglandins of the E1 series

The structure has been established and stereochemical assignments have been made of two complete sets of diastereomers of the 7-thia and 13-thia analogs of 11-deoxy-prostaglandins of the E₁ series by the¹³C NMR method. It is proposed to determine the diastereomeric effects of the¹³C NMR chemical shifts, which are differential parameters bearing information on the stereochemistry of the molecules. Diagnostic diastereomeric effects have been found for assigning stereoisomers with respect to the C-15-hydroxy group and also with respect to the C-8 and C-12 chiral centers of the cyclopentane ring.Institute of Chemistry of the Bashkir Branch of the USSR Academy of Sciences, Ufa. Translated from Khimiya Prirodnykh Soedinenii, No. 2, pp. 282–287, March–April, 1988.     

1H- und 13C-NMR-Untersuchungen zur Struktur N-substituierter Tetrazole—Die Strukturen des N-Methoxycarbonyl-, N-Acetyl- und N-(Tri-n-butylstannyl)-tetrazols sowie Substituenteneffekte auf δ13C und 1J(CH)

The ¹H and ¹³C NMR spectra of several isomeric N-substituted tetrazoles have been investigated. ¹³C NMR is shown to be more useful for distinguishing between structural isomers of N-substituted tetrazoles except for those carrying electropositive substituents like SnBu₃. Correlations of δC-5 (inverse) and ¹J(C-5,H) with s?₁ found for 1-substituted tetrazole allowed the identification of the N SnBu₃ derivative as 1-(tri-n-butylstannyl)tetrazole. The phenyl carbon chemical shift difference ΔC′ = δC-3′-δC-2′ is insignificant for structure elucidation and conformational studies of N-substituted 5-phenyltetrazoles; ΔH′ from ¹H NMR spectra seems to be more useful.     

1H, 13C and 77Se NMR spectra of substituted selenoanisoles

The ¹H, ¹³C and ⁷⁷Se chemical shifts and the ¹J[C(Me)H(Me)], ^1.2J(SeC) and ²J(SeH) coupling constants in 14 para- or meta-substituted selenoanisoles, R? C₆H₄? Se? CH₃, have been measured and the dependence of these parameters on the electronic effects of the substituent R is discussed. A significant (up to 6 ppm) deviation from additivity of the substituent influence on the shielding of the ¹³C ring carbons has been found.     

13C13C spin coupling constants in phenanthrene derivatives

The synthesis of six 1-X- (X = OH, OCH₃, OCOCH₃, CH₃, CHO and CN) phenanthrene derivatives with a ¹³C label at C-1 is described. An analysis of the ¹³C¹³C spin coupling constants shows the importance of π-interaction for the coupling constant transmission. Small ¹³C¹³C spin coupling constants over 6 bonds are reported.     

Polyhaloheterocyclic compounds. Part XXXI—carbon-13 NMR spectra as a structural probe for polychloroaromatic compounds

Carbon-13 spectra of twelve chlorofluoropyridines (C₅CI_nF_5?nN), of known structure, have been assigned and an assessment has been made of the degree of additivity of substituent chemical shifts (SCS). Reasonable additivity is observed for pyridine derivatives but little regulatiry can be inferred from the spectra of perchlorinated-diazines and -triazines. There is an approximately linear relationship between ¹³C and ¹⁹F chemical shifts.     

Natural Abundance 13C-NMR. of Vitamin D3 Metabolites

Chemical shifts of ¹³C- and ¹H-NMR. spectra of vitamin D₃ metabolites ( 2–7 ) are assigned. Substituent effect parameters due to hydroxyl groups are deduced by comparison with vitamin D₃.     

Long range carbon—carbon coupling in olefins. 4-13C-4-propyl-3-heptene and 1-13C-1-methylcyclohexene

All ¹³C—¹³C splittings involving the C-4 carbon of 4-propyl-3-heptene and the C-1 carbon of 1-methylcyclohexene were determined from the appropriately labeled (> 90%-¹³C) derivatives. The observed trends in coupling constants continue to offer additional means of carbon chemical shift assignments and to provide mechanistic information regarding the nature of long range carbon—carbon coupling.     

Investigation of benzimidazoles. III—transmission of the substituent effects in 2-substituted 1-methylbenzimidazoles studied by 13C nuclear magnetic resonance

The influence of substituents on the ¹³C NMR chemical shifts of 2-substituted 1-methylbenzimidazoles has been investigated. The electronic effects of the substituents are transmitted to C-4 and C-7 mainly by the resonance mechanism, and to C-5, C-6 and N-CH₃, by approximately equal contributions of the resonance and inductive components. A critical analysis of the share in the transmission of substituent effects through the ‘pyridine-type’ and ‘pyrrole-type’ nitrogen atoms is given.