Long-range 1H-15N two-dimensional heteronuclear shift correlation of the alkaloid vincamine at natural abundance

Long-range ¹H-¹⁵N heteronuclear correlation pathways in the alkaloid vincamine, a structural constituent or biogenetic congener of numerous Vinca alkaloids, are reported. Correlations were observed through the use of the GHNMQC (Gradient-enhanced Hydrogen-Nitrogen Multiple Quantum Coherence) 2D nmr experiment at natural abundance. An unanticipated four-bond coupling between the H15a resonance and N4 was observed in contrast to the typical two- and three-bond coupling pathways. Nitrogen-15 chemical shift comparisons are drawn between vincamine and structurally related alkaloids including ajmaline and the velbanamine portion of the semi-synthetic alkaloid vinorelbine (Navelbine^TM).     

Long-range 1H-15N correlation at natural abundance using gradient-enhanced inverse-detection

Inverse-detected heteronuclear shift correlation efficiency has been significantly augmented by the incorporation of pulsed field gradients (PFG). Phase-cycling requirements for t₁-noise suppression in gradient-enhanced experiments are, for the most part, obviated, making it feasible to acquire data in one or a few transients/t₁ increment. The benefits which acerue for ¹H-¹³C correlation (using GHMQC, GHMBC, and variants of GHMQC-TOCSY) are well documented. Less obvious is the increased facility with which long-range ¹H-¹⁵N correlation spectra can be acquired. An IDR-(Inverted Direct Response)-GHMQC-TOCSY was used to establish unequivocal proton resonance assignments for the alkaloid ajmaline. Long-range ¹H-¹⁵N heteronuclear couplings to the two nitrogen atoms of ajmaline were then probed using a gradient-enhanced ¹H-¹⁵N heteronuclear shift correlation experiment derived from HMQC. Long-range ¹H-¹⁵N couplings in ajmaline are assigned for the first time.     

Long-range 1H-15N couplings and 15N chemical shift assignments of the bis-indole anticancer drug navelbine®

The recently reported application of gradient-enhanced HMQC for the observation of long-range ¹H-¹⁵N heteronuclear couplings at natural abundance has been extended to the bis-indole anticancer drug Navelbine®. Responses correlating protons to N16′ (δ ¹⁵N 138.2 ppm)in the velbanamine subunit and N1 and N9 (δ ¹⁵N 66.0 and 55.3 ppm, respectively) in the vindoline subunit were observable within about 4 hours of data acquisition. The single response to N6′ (δ ^I5N 43.0 ppm), in contrast, was very weak requiring a weekend data acquisition to even be observed. The difficulty in observing correlations to N6′ is presumably a function of molecular mobility in the eight-membered azocine ring.     

Spin-spin coupling constants 13C-15N and 1H-15N in the investigation of azido-tetrazole tautomerism in a series of 2-azidopyrimidines

A new method was developed for the investigation of an azido-tetrazole equilibrium based on using a complex analysis of ¹³C-¹⁵N and ¹H-¹⁵N spin-spin coupling constants. The use of this approach became possible due to the selective inclusion of ¹⁵N isotopes into the structures of 2-azidopyrimidines and their cyclic analogs tetrazolo[1,5-a]pyrimidines.     

13C, 15N coupling constants in substituted 1,2,4-triazines-4-15N

The ¹³C,¹⁵N coupling constants in three 1,2,4-triazine-4-¹⁵N derivatives and in a substituted pyrimidine-1-¹⁵N have been determined and are compared with those in pyridine and quinoline. Of special interest are the data of the 5-(2-dimethylamino-1-propenyl)-3,6-dimethyl-1,2,4-triazine-4-¹⁵N, since one observes a characteristic alternation of the absolute value of J(¹³C,¹⁵N) along the sidechain and a hitherto unobserved very large ¹³C,¹⁵N coupling constant through four bonds of 3·9 Hz, the origin of which is attributed to the influence of the lone pair orbital on the ¹⁵N at position 4.     

15N NMR Study of Coordinated Amine,Aminocarbyne, and Carboxamido Groups in Triosmium Clusters

The ¹⁵N NMR spectra of the complexes Os₃(CO)₁₀(μ₂-CONHPrⁱ)(μ₂-C? NHR) (1a, R = Pr; 1b, R = CH₂Ph) and Os₃(CO)₉(NH₂Prⁱ)(μ₂-CONHPrⁱ)(μ₂-C? NHR) (2a, R = Pr; 2b, R = CH₂Ph) are studied by using the ¹H detected (inverse) ¹H-¹⁵N correlated spectroscopy. The ¹⁵N chemical shifts and the ¹H-¹⁵N coupling constants fall in characteristic regions for each of the coordinated amine, aminocarbyne, and carboxamido ligands and these values are related to their bonding types. The NMR data are discussed in terms of the influence of the paramagnetic term which is the major factor determining the chemical shifts. A comparison is made to understand the ¹⁵N chemical-shift differences between the coordinated nitrogen-containing ligands and the corresponding free organic molecules.     

Carbon-13 chemical shifts and 13C?15N coupling constants of 3,4-dihydroisoquinoline-15N,its 15N-oxide and their conjugate acids

On protonation of 3,4-dihydroisoquinoline-¹⁵N ¹J(¹³C—1, ¹⁵N) is increased by a factor of five and ¹J(¹³C—3, ¹⁵N) changes its sign, while on protonation of 3,4-dihydroisoquinoline-¹⁵N-oxide the coupling constants, including the relatively large ¹J(¹³C—1, ¹⁵N), remain practically constant, although significant alterations of the ¹³C chemical shifts take place.     

NMR studies in the heterocyclic series XXIV—1H, 13C and 15N study of 15N labelled indazoles

The ¹⁵N chemical shifts and ¹H? ¹⁵N and ¹³C? ¹⁵N coupling constants of nine monolabelled indazoles were measured and assigned. The experimental values are discussed in terms of the indazolic and iso-indazolic structures, and compared with literature data for other related heterocycles. All the results are consistent with an N-1(H) tautomeric structure for indazole in DMSO-d₆.     

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.     

An Efficient Synthesis of [15N]-Carbazole from [15N]-Aniline

A reaction sequence involving ortho-lithiation of [¹⁵N]-(tert-Butoxy-carbonyl)aniline, quenching with Bu₃SnCl, palladium catalyzed coupling with bromobenzene, and deprotection provides efficient access to [¹⁵N]-2-aminobiphenyl (4). Compound 4 is converted to [¹⁵N]-carbazole via diazotization, treatment with NaN₃, and heating to promote intramolecular nitrene insertion.     

Dynamic 15N NMR studies of iron phosphine complexes containing coordinated dinitrogen

The ¹⁵N‐labelled iron dinitrogen complexes trans‐[FeH(N₂)(PP)₂]⁺[BPh₄]^? (PP = dppe, depe, dmpe) and cis‐[FeH(N₂)(PP₃)]⁺[BPh₄]^? were prepared in situ by exchange of unlabelled coordinated dinitrogen with ¹⁵N₂. ¹⁵N NMR chemical shifts and coupling constants are reported. The ¹⁵N spectra exhibit separate signals for the metal‐bound and terminal nitrogen atoms of the coordinated N₂. The ¹⁵N resonances display ¹⁵N, ¹⁵N coupling as well as ³¹P, ¹⁵N coupling and long‐range ¹⁵N, ¹H coupling when there is a metal‐bound hydrido ligand. Exchange between free and coordinated dinitrogen was monitored by magnetization transfer between ¹⁵N‐labelled sites using an inversion–transfer–recovery experiment. Exchange between the metal‐bound and terminal nitrogen atoms of coordinated N₂ was also monitored by magnetization transfer and this could proceed by N₂ dissociation or by an intramolecular process. Copyright © 2003 John Wiley & Sons, Ltd.     

NMR investigations on alanyl-[15% 13C, 95% 15N]-proline: 15N chemical shifts and 13C?15N coupling constants

The dipeptide alanylproline has been prepared with the proline residue both ¹³C (15%) and ¹⁵N (95%) enriched. ¹⁵N NMR spectra of alanylproline reveal signals for both possible conformations—cis and trans—of the dipeptide backbone in solution. Different pK values for both conformers are obtained from the pH dependence of the ¹⁵N chemical shifts using a least square programme based on the Henderson–Hasselbach equation. These different values are discussed in terms of interaction between the α-amino group and the carboxylate group and between the carboxylate oxygen and the carbonyl oxygen of the dipeptide via hydrogen bonding. Further evidence for these interactions is obtained from the pH dependence of the ratio of the ¹⁵N NMR signal intensities of the two conformers. One, two or three bonded ¹³C? ¹⁵N coupling constants measured in the ¹³C NMR high resolution spectra have different values in the cis and trans isomers of alanylproline and thus indicate different geometry in the pyrrolidine ring.     

Application of 13C and 15N NMR spectroscopy to structural studies on nitramines

¹⁵N and ¹³C chemical shifts and the ¹J(¹⁵N¹⁵N), ¹J(¹⁵N¹³C) and ¹J(¹³CH) coupling constants have been determined for a number of ¹⁵N-enriched cyclic and acyclic secondary nitramines. The results are interpreted in terms of both electronegativity effects and conformational factors.     

Analysis of fine splittings in the fourier transform 1H magnetic resonance spectra of some 15N labeled borazine derivatives

Proton NMR spectra are reported for ¹⁵N enriched borazine and a series of ¹⁵N enriched derivatives: N-methyl-borazine, N,N′-dimethylborazine and a new photochemical product, 1-methyl-2-aminoborazine. Chemical shifts for the ring (¹⁵N? H) protons have been measured. Using a Fourier transform spectrometer, fine structure in the ¹⁵N? H doublet is resolved. Ortho and meta ring proton and three-bond ¹⁵N to H coupling constants have been determined. Substituent effects on chemical shifts and coupling constants for borazine derivatives are compared with those for analogous benzene derivatives.     

Assignment of oxime and hydrazone configuration using 1H‐15N and 13C‐15N coupling measurements at natural abundance

Measurement of ¹H‐¹⁵N and ¹³C‐¹⁵N coupling constants at natural abundance is demonstrated to be a reliable and generic method to determine the configuration of oximes, hydrazines, and related systems. Data on ¹H‐¹⁵N and ¹³C‐¹⁵N coupling constants on a variety of systems obtained at natural abundance confirm the geometric dependence of the measured ¹H‐¹⁵N and ¹³C‐¹⁵N coupling constants. In addition, we summarize a simple “decision‐tree” for determining configuration based on practical considerations of sample quantity, solubility, and complexity. Copyright © 2016 John Wiley & Sons, Ltd.     

15N chemical shifts and one bond 15N?1H coupling constants in simple amides

An indirect method is employed for determining the ¹⁵N parameters at the natural abundance level in a series of simple acyclic and cyclic amides. The one bond coupling constant, ¹J(¹⁵N¹H), and the ¹⁵N chemical shift are measured as a function of the carbonyl substituent group or the ring size and the nature of the solvent (CCl₄ or H₂O). These ¹⁵N parameters are related to the amide bond structure, the nitrogen configuration and possible intermolecular hydrogen bonding (amide-amide or amide-water).     

One-bond 1J(15N─19F) spin–spin coupling constants of cationic fluorinating reagents: Insights from DFT calculations

We have investigated, by means of density functional theory protocols, the one-bond ¹J(¹⁵N─¹⁹F) spin–spin coupling constants in a series of fluorinating reagents, containing the N─F bond, recently studied experimentally. The results of the calculations show a very good linear relationship with the experimental values, even though only the M06-2X(PCM)/pcJ-2//B3LYP/6-311G(d,p) level affords a very low mean absolute error. The calculations allow to analyze the various molecular orbitals contributions to the J coupling and to rationalize the observed positive sign, corresponding to a negative sign of the reduced spin–pin coupling constant K(N─F). Moreover, of the four Ramsey contributions, only the diamagnetic spin orbit is negligible, whereas the paramagnetic spin orbit and spin dipole terms decrease the magnitude of the Fermi contact (FC) term by an amount that goes from a minimum of 35% up to more than 60% of the FC term itself. Several effects have been investigated, namely, the contribution of the long-range solvent reaction field, relativistic corrections, and conformational and vibrational effects.     

15N13C coupling constants in 15N labelled azaadamantane

The ¹⁵N¹³C coupling constants in ¹⁵N labelled azaadamantane have been measured and interpreted in terms of their conformational dependence as compared with ¹⁵N-quinuclidine.     

Proton polarization transfer in natural abundance 15N NMR studies of E- and Z-isomers of N-alkylformamides

Proton polarization transfer has been used for the convenient observation of proton coupled natural abundance ¹⁵N NMR spectra of the E- and Z-isomers of N-methylformamide at 10.14 MHz. Second-order spectral analysis is required to determine the ¹⁵N? H coupling constants, at least for the E-isomer of secondary formamides. An useful stereospecificity is observed for both the one- and two-bond ¹⁵N? H coupling constants.     

The B–N Bond in Some Aminoboranes and an Iminoborane,Studied by 11B and 15N NMR Spectroscopy and DFT Methods

¹⁵N NMR spectra of several aminoboranes (Me₂B–NMe₂, Cl₂B–NMe₂, Br₂B–NMe₂, OCH₂CH₂OB–NMe₂), three N‐pyrrolylboranes, and an iminoborane (tBu–B≡N–tBu) was measured. The spin‐spin coupling constants ¹J(¹⁵N, ¹¹B) were resolved at elevated temperatures. In the case of the iminoborane at 105 °C, the coupling constant ¹J(¹⁴N,¹¹B) = 57 Hz could also be determined from the ¹¹B NMR spectrum [from ¹⁵N NMR ¹J(¹⁵N,¹¹B) = 81 Hz]. Generally, there is no correlation between the magnitude of ¹J(¹⁵N,¹¹B) and the bond length d_BN. The values ¹J(¹⁵N,¹¹B) indicate that changes in σ bonding affect their magnitude, and the nature of the lone pair of electrons at nitrogen is of great importance. The calculated NMR parameters of an adduct of the iminoborane with an N‐heterocyclic carbene, show that the bonding situation around the BN double bond in the adduct is comparable with imines.