Through‐space 19F–15N couplings for the assignment of stereochemistry in flubenzimine

Through‐space ¹⁹F–¹⁵N couplings revealed the configuration of flubenzimine, with the CF₃ group on N4 pointing towards the lone pair of N5. The ¹⁹F–¹⁵N coupling constants were measured at natural abundance using a spin‐state selective indirect‐detection pulse sequence. As ¹⁵N‐labelled proteins are routinely synthesized for NMR studies, through‐space ¹⁹F–¹⁵N couplings have the potential to probe the stereochemistry of these proteins by ¹⁹F labelling of some amino acids or can reveal the site of docking of fluorine‐containing drugs. Copyright © 2016 John Wiley & Sons, Ltd.     

Exploiting natural abundance 13C–15N coupling as a method for identification of nitrogen heterocycles: practical use of the HCNMBC sequence

In this paper, we detail the results of ¹H–¹⁵N correlation data obtained via ¹³C–¹⁵N coupling at natural abundance on a number of classes of azoles including pyrazoles, imidazoles and triazoles. The experiment produces data that is highly complementary to direct ¹H–¹⁵N HMBC type correlations in that it can provide ¹⁵N chemical shift data for nitrogen that may not show up in the HMBC. This is particularly advantageous in the triazoles where ¹⁵N chemical shift can be diagnostic of regiochemistry. Because of the consistency in J_CN values among the azoles, the experiment produces distinctive correlation patterns that can be used for identification of regiochemistry. The experiment can also be used to directly measure ¹³C–¹⁵N coupling constants. Copyright © 2015 John Wiley & Sons, Ltd.     

Modern proton‐detected 1D 1H–15N NMR experiments. Application to the measurement of 1H,15N coupling constants at natural abundance

Non‐selective and selective versions of several proton‐detected 1D NMR experiments to be applied to ¹⁵N are proposed. Clean, artifact‐free 1D spectra are easily obtained by the effective coherence selection by pulsed‐field gradients and the attainable sensitivity is maximized using modern pulse schemes. Despite the low sensitivity inherent to ¹⁵N NMR spectroscopy, the successful application of these experiments is demonstrated for resonance assignments and accurate measurement of both one‐bond and long‐range proton–nitrogen coupling constants on a model tripeptide at natural abundance. Copyright © 2001 John Wiley & Sons, Ltd.     

1H‐, 13C‐, and 15N‐NMR chemical shifts for selected glucosides and ribosides of aromatic cytokinins

The ¹H and ¹³C NMR resonances of 16 purine glucosides were assigned by a combination of one‐ and two‐dimensional NMR experiments, including gs‐COSY, gs‐HSQC, and gs‐HMBC, in order to characterize the effect of substituent and the position of glucose unit on the NMR chemical shifts. In addition, ¹⁵N NMR chemical shifts for selected derivatives were investigated by using ¹H? ¹⁵N chemical shift correlation techniques. To map the influence of sugar moiety on the directly bonded nitrogen atom, selected N⁹‐glucosides and their ribose analogs were compared. Characteristic long‐range ¹H? ¹⁵N coupling constants, measured by using ¹H? ¹⁵N gradient‐selected single‐quantum multiple bond correlation (GSQMBC), are also reported and discussed. All compounds investigated here belong to cytokinins, an important group of plant hormones. Copyright © 2010 John Wiley & Sons, Ltd.     

15N and 13C NMR chemical shifts of 6‐(fluoro,chloro, bromo,and iodo)purine 2′‐deoxynucleosides: measurements and calculations

The ¹⁵N and ¹³C chemical shifts of 6‐(fluoro, chloro, bromo, and iodo)purine 2′‐deoxynucleoside derivatives in deuterated chloroform were measured. The ¹⁵N chemical shifts were determined by the ¹H? ¹⁵N HMBC method, and complete ¹⁵N chemical‐shift assignments were made with the aid of density functional theory (DFT) calculations. Inclusion of solvation effects significantly improved the precision of the calculations of ¹⁵N chemical shifts. Halogen‐substitution effects on the ¹⁵N and ¹³C chemical shifts of purine rings are discussed in the context of DFT results. The experimental coupling constants for ¹⁹F interacting with ¹⁵N and ¹³C of the 6‐fluoropurine 2‐deoxynuleoside are compared with those from DFT calculations. Copyright © 2009 John Wiley & Sons, Ltd.     

Structural and conformational analysis of 1‐oxaspiro[2.5]octane and 1‐oxa‐2‐azaspiro[2.5]octane derivatives by 1H, 13C,and 15N NMR

A structural and conformational analysis of 1‐oxaspiro[2.5]octane and 1‐oxa‐2‐azaspiro[2.5]octane derivatives was performed using ¹H, ¹³ C, and ¹⁵ N NMR spectroscopy. The relative configuration and preferred conformations were determined by analyzing the homonuclear coupling constants and chemical shifts of the protons and carbon atoms in the aliphatic rings. These parameters directly reflected the steric and electronic effects of the substituent bonded to the aliphatic six‐membered ring or to C3 or N2. The parameters also were sensitive to the anisotropic positions of these atoms in the three‐atom ring. The preferred orientation of the exocyclic substituents directed the oxidative attack. Copyright © 2012 John Wiley & Sons, Ltd.     

15N NMR of 1,4‐dihydropyridine derivatives

In this article, we describe the characteristic ¹⁵N and ¹H_N NMR chemical shifts and ¹J(¹⁵N–¹H) coupling constants of various symmetrically and unsymmetrically substituted 1,4‐dihydropyridine derivatives. The NMR chemical shifts and coupling constants are discussed in terms of their relationship to structural features such as character and position of the substituent in heterocycle, N‐alkyl substitution, nitrogen lone pair delocalization within the conjugated system, and steric effects. Copyright © 2013 John Wiley & Sons, Ltd.     

Derivatives of pyrazinecarboxylic acid: 1H, 13C and 15N NMR spectroscopic investigations

NMR spectroscopic studies are undertaken with derivatives of 2‐pyrazinecarboxylic acid. Complete and unambiguous assignment of chemical shifts (¹H, ¹³C, ¹⁵N) and coupling constants (¹H,¹H; ¹³C,¹H; ¹⁵N,¹H) is achieved by combined application of various 1D and 2D NMR spectroscopic techniques. Unequivocal mapping of ¹³C,¹H spin coupling constants is accomplished by 2D (δ,J) long‐range INEPT spectra with selective excitation. Phenomena such as the tautomerism of 3‐hydroxy‐2‐pyrazinecarboxylic acid are discussed. Copyright © 2009 John Wiley & Sons, Ltd.     

Characterization of 2‐aryl‐1,3,4‐oxadiazoles by 15N and 13C NMR spectroscopy

¹⁵N NMR chemical shifts of 2‐aryl‐1,3,4‐oxadiazoles were assigned on the basis of the ¹H–¹⁵N HMBC experiment. Chemical shifts of the nitrogen and carbon atoms in the oxadiazole ring correlate with the Hammett σ‐constants of substituents in the aryl ring (r² ≥ 0.966 for N atoms). ¹⁵N NMR data are a suitable and sensitive means for characterizing long‐range electronic substituent effects. Additionally, ¹³C NMR data for these compounds are presented. Copyright © 2003 John Wiley & Sons, Ltd.     

Heterocyclic analogs of xanthiones: 5,6‐fused 3‐methyl‐1‐phenylpyrano[2,3‐c]pyrazol‐4(1H) thiones—synthesis and NMR (1H, 13C, 15N) data

Various [5,6]pyrano[2,3‐c]pyrazol‐4(1H)‐thiones were synthesized in high yields by treatment of the corresponding [5,6]pyrano[2,3‐c]pyrazol‐4(1H)‐ones with Lawesson's reagent. Detailed NMR spectroscopic studies were undertaken of the title compounds. Complete and unambiguous assignment of chemical shifts (¹H, ¹³C, ¹⁵N) and coupling constants (¹H,¹H; ¹³C,¹H) was achieved by the combined application of various one‐ and two‐dimensional (1D and 2D) NMR spectroscopic techniques. Unequivocal mapping of most ¹³C,¹H spin coupling constants is accomplished by 2D (δ, J) long‐range INEPT spectra with selective excitation. Copyright © 2010 John Wiley & Sons, Ltd.     

N7‐ and N9‐substituted purine derivatives: a 15N NMR study

The ¹⁵N NMR chemical shifts of N⁷‐ and N⁹‐substituted purine derivatives were investigated systematically at the natural abundance level of the ¹⁵N isotope. The NMR chemical shifts were determined and assigned using GSQMBC, GHMBC, GHMQC and GHSQC experiments in solution. ¹⁵N cross‐polarization magic angle spinning data were recorded for selected compounds in order to study the principal values of the ¹⁵N chemical shifts. Geometric parameters obtained by using RHF/6–31G** and single‐crystal x‐ray structural analysis were used to calculate the chemical‐shielding constants (GIAO and IGLO) which were then used to assign the nitrogen resonances observed in the solid‐state NMR spectra and to determine the orientation of the principal components of the shift tensors. Copyright © 2002 John Wiley & Sons, Ltd.     

Theoretical and experimental 1H, 13C and 15N NMR studies of N‐alkylation of substituted tetrazolo[1,5‐a]pyridines

The ¹⁵N as well as ¹H and ¹³C chemical shifts of nine substituted tetrazolopyridines and their corresponding tetrazolopyridinium salts have been determined by using NMR spectroscopy at the natural abundance level of all nuclei in CD₃CN. In this paper, we report, for the first time, the N‐alkylation reaction of electron deficient tetrazolopyridines. The treatment of tetrazolopyridines 5–13 with one equivalent of trialkyloxonium tetrafluoroborate leads to a mixture of two isomers, i.e. N3‐ and N2‐alkyl tetrazolo[1,5‐a]pyridinium salts. It has been observed that the N3‐isomer is always the major isomer, except in the case of the CF₃ substituent, where the two isomers are obtained in the same amount. The quaternary tetrazolopyridinium nitrogen N3 is shielded by around 100 ppm (parts per million) with respect to the parent tetrazolopyridine. Experimental data are interpreted by means of density functional theory (DFT) calculations, including solvent‐induced effects, within the conductor‐like polarizable continuum model (CPCM). Good agreements between theoretical and experimental ¹H, ¹³C and ¹⁵N NMR were found. The combination of multinuclear magnetic resonance spectroscopy with gauge including atomic orbital (GIAO) DFT calculations is a powerful tool in the structural elucidation for both neutral and cationic heterocycles and in the determination of the orientation of N‐alkylation of tetrazolopyridines. Copyright © 2009 John Wiley & Sons, Ltd.     

Characterization of para‐substituted benzamidoximes and benzamidinium salts by 15N NMR spectroscopy

¹⁵N NMR data for a series of 12 para‐substituted benzamidoximes and benzamidinium salts were determined in dimethyl sulfoxide. For the amino group of benzamidoximes ¹J(N,H) coupling constants were determined using polarization transfer techniques; the other ¹⁵N atoms were not detectable owing to fast exchange processes and, thus, standard proton noise decoupled spectra had to be measured. The ¹⁵N NMR chemical shifts of the oxime‐type nitrogen atom and the benzamidinium amino group (with two exceptions) correlate with Hammett σ° values (r²>0.95). ¹⁵N NMR shift data are a suitable and sensitive means for characterizing far‐ranging electronic substituent effects in these functional groups. Additionally, ¹³C NMR data in dimethyl sulfoxide solution are given. All spectroscopic data will be used for investigations into the mechanisms of the enzymes involved in the metabolic cycle of oxidation and reduction of benzamidines and benzamidoximes. Copyright © 2002 John Wiley & Sons, Ltd.     

Position-specific 15N isotope analysis in organic molecules: A high-precision 15N NMR method to determine the intramolecular 15N isotope composition and fractionation at natural abundance

The position-specific ¹⁵N isotope content in organic molecules, at natural abundance, is for the first time determined by using a quantitative methodology based on ¹⁵N Nuclear Magnetic Resonance (NMR) spectrometry. ¹⁵N NMR spectra are obtained by using an adiabatic “Full-Spectrum” INEPT sequence in order to make possible ¹⁵N NMR experiments with a high signal-to-noise ratio (>500), to reach a precision with a standard deviation below 1‰ (0.1%). This level of precision is required for observing small changes in ¹⁵N content associated to ¹⁵N isotope effects. As an illustration, the measurement of an isotopic enrichment factor ε for each ¹⁵N isotopomer is presented for 1-methylimidazole induced during a separation process on a silica column. The precision expressed as the long-term repeatability of the methodology is good enough to evaluate small changes in the ¹⁵N isotope contents for a given isotopomer. As observed for ¹³C, inverse and normal ¹⁵N isotope effects occur concomitantly, giving access to new information on the origin of the ¹⁵N isotope effects, not detectable by other techniques such as isotope ratio measured by Mass Spectrometry for which bulk (average) values are obtained.     

Multinuclear magnetic resonance studies of 2‐aryl‐1,3,4‐selenadiazoles

2‐Aryl‐1,3,4‐selenadiazoles were studied by ¹H, ¹³C, ¹⁵N and ⁷⁷Se NMR spectroscopy. The results (chemical shifts and coupling constants) were correlated with Hammett substituent parameters as well as calculated chemical shifts and bond lengths. Copyright © 2012 John Wiley & Sons, Ltd.     

1H{15N} GHMQC study of 5,7‐diphenyl‐1,2,4‐triazolo[1,5‐a]pyrimidine and 1H, 13C and 15N NMR coordination shifts in Au(III) chloride complexes of 1,2,4‐triazolo[1,5‐a]pyrimidines

The ¹H{¹⁵N} NMR spectrum of 5,7‐diphenyl‐1,2,4‐triazolo[1,5‐a]‐pyrimidine ( 3 ) was measured by GHMQC, unambiguously assigned and compared with the spectra of 1,2,4‐triazolo[1,5‐a]pyrimidine ( 1 ) and 5,7‐dimethyl‐1,2,4‐triazolo[1,5‐a]pyrimidine ( 2 ). A series of Au(III) chloride complexes of general formula AuLCl₃, where L = 1 , 2 , 3 , was synthesized and studied by ¹HH{¹⁵N} GHMQC and ¹H{¹³C} GHMBC. Low‐frequency shifts of 72–74 ppm (¹⁵N) and 5–6 ppm (¹³C) were observed upon complexation by Au(III) ions for the coordination site N‐3 and adjacent C‐2, C‐3a atoms, respectively. The ¹³C signals of C‐5, C‐6, C‐7 and the ¹H resonances of H‐2, H‐6 were shifted to higher frequency. Comparison with analogous Pd(II), Pt(II) and Pt(IV) complexes revealed that in the case of Au(III) coordination the ¹⁵N shifts were relatively smaller, whereas those for ¹³C and ¹H were larger. Copyright © 2002 John Wiley & Sons, Ltd.     

1H, 13C and 15N NMR spectral assignments for new triazapentalene derivatives

Mesomeric heteropentalene betaines are conjugated fused polyheterocyclic structures that represent interesting intermediates for organic synthesis. Five such structures, containing at least four nitrogen atoms and various substituents, have been characterized by ¹H, ¹³C and ¹⁵N NMR. We report, apparently for the first time, nitrogen NMR data and coupling information on such systems. Inter‐ring long‐range correlations across five bonds with ¹⁵N (⁵J_HN) and up to seven bonds with ¹³C (⁶J_HC and ⁷J_HC) were observed in HSQC experiments. The incorporation of an electron‐withdrawing substituent such as NO₂ was observed to cause an increase in the magnitude of the remote couplings and deshielding of nearby protons, carbons and on all nitrogen atoms of the structure, including remote ones situated on other cycles. Copyright © 2009 John Wiley & Sons, Ltd.     

1H, 13C and 15N NMR spectroscopic characterization of unexpected degradation products of the nifedipine analogue bis(2‐cyanoethyl) 2,6‐dimethyl‐4‐(2‐nitrophenyl)‐1,4‐dihydro‐3,5‐pyridinedicarboxylate

In the course of saponification experiments with bis(2‐cyanoethyl) 2,6‐dimethyl‐4‐(2‐nitrophenyl)‐1,4‐dihydro‐3,5‐pyridinedicarboxylate ( 1 ), an analogue of the calcium channel blocker nifedipine, three unexpected degradation products were isolated. The compounds were identified as 3‐(2‐acetamido‐1‐carboxy‐1‐propenyl)‐1‐hydroxy‐2‐indolecarboxylic acid ( 3 ), 9‐hydroxy‐1,3‐dimethyl‐β‐carboline‐4‐carboxylic acid ( 4 ) and 6‐hydroxy‐2,4‐dimethyl‐5‐oxo‐5,6‐dihydrobenzo[c][2,7]naphthyridine‐1‐carboxylic acid ( 6 ). The structures of these compounds were deduced from one‐ and two‐dimensional ¹H, ¹³C and natural abundance ¹⁵N NMR experiments (¹H,¹H‐COSY, gs‐HSQC, gs‐HMBC, ¹⁵N gs‐HMBC), and corroborated by comparison of their NMR data with the respective data for structurally similar compounds. Copyright © 2002 John Wiley & Sons, Ltd.     

1H, 13C and 15N NMR chemical shifts of substituted pyrazolo[1,5‐a]pyrimidines

¹H, ¹³C and ¹⁵N NMR chemical shifts of 10 substituted pyrazolo[1,5‐a]pyrimidines were assigned based on DQF ¹H, ¹H COSY, PFG ¹H, ¹³C HMQC and PFG ¹H,X (X = ¹³C and ¹⁵N) HMBC experiments and on literature data. Copyright © 2002 John Wiley & Sons, Ltd.     

1H, 13C and 15N NMR assignments for N‐ and O‐acylethanolamines,important family of naturally occurring bioactive lipid mediators

The complete ¹H, ¹³C and ¹⁵N NMR signal assignments of some N‐ and O‐acylethanolamines, important family of naturally occurring bioactive lipid mediators, were achieved using one‐dimensional and two‐dimensional experiments (gs‐HMQC and gs‐HMBC). Copyright © 2012 John Wiley & Sons, Ltd.