Complete assignments of the 1H and 13C NMR spectra of 15 limonoids

Unambiguous and complete assignments of ¹H and ¹³C NMR chemical shifts for 15 limonoids, eight of them found in natural sources and seven other synthetic derivatives, are presented. The assignments are based on 2D shift‐correlated [¹H,¹H‐COSY, ¹H,¹³C‐gHSQC‐¹J(C,H), ¹H,¹³C‐gHMBC‐ⁿJ(C,H) (n = 2 and 3)] and NOE experiments. Copyright © 2003 John Wiley & Sons, Ltd.     

Complete 1H and 13C NMR assignments of three labdane diterpenoids isolated from Leonotis ocymifolia and six other related compounds

Unambiguous and complete assignments of ¹H and ¹³C NMR chemical shifts for three structurally complex labadane diterpenoids isolated from Leonotis ocymifolia (leonotin, leonotinin and nepetaefolin) and six other related compounds (hispanolone, 7α‐ and 7β‐hispanols, marrubiin, villenol and andalusol), previously isolated from Labiatae species, are presented. The assignments are based on 2D shift‐correlated [¹H, ¹H‐COSY, ¹H, ¹³C‐gHSQC–¹J(C,H), ¹H,¹³C‐gHMBC–ⁿJ(C,H) (n = 2 and 3)] and DPFGSE 1D‐NOE experiments. Copyright © 2003 John Wiley & Sons, Ltd.     

1H and 13C NMR spectral characterization of some antimalarial in vitro 2,4‐diamino‐10‐methylpyrimido[4,5‐b]‐5‐quinolone derivatives

We report the ¹H NMR and ¹³C NMR chemical shifts and J(H,H), J(H,F) and J(C,F) coupling constants of 13 2,4‐diamino‐10‐methylpyrimido[4,5‐b]‐5‐quinolone derivatives, some of them with moderate activity against Plasmodium falciparum in vitro. They were characterized and assigned on the basis of ¹H, ¹³C and ¹³C–¹H (short‐ and long‐range) correlated spectra. Copyright © 2002 John Wiley & Sons, Ltd.     

Complete assignments of the 1H and 13C NMR spectra of five rearranged abietane diterpenoids

An NMR study of five highly functionalized and rearranged abietane diterpenoids is described. In addition to 1D NMR methods, including 1D NOESY spectra, 2D shift‐correlated experiments [¹H, ¹³C‐gHSQC‐¹J (C,H) and ¹H, ¹³C‐gHMBC‐ⁿJ (C,H) (n = 2 and 3)] were used for the complete and unambiguous ¹H and ¹³C chemical shift assignments of these substances. Copyright © 2002 John Wiley & Sons, Ltd.     

Indirect detection of 31P,X connectivities with proton sensitivity: application of two‐dimensional 31P‐relayed 1H,X correlation spectroscopy

Experiments for ¹H‐detected heteronuclear ¹H,X correlation spectroscopy with ³¹P‐relayed coherence transfer are described which allow the indirect detection of δX and ⁿJ(X,P) even in the absence of a direct J(X,H) coupling. The use of these techniques for the assignments of ¹³C, ¹⁵N, and ¹⁸³W NMR data of organophosphorus compounds is demonstrated. Copyright © 2003 John Wiley & Sons, Ltd.     

Detailed assignments of 1H and 13C NMR spectral data of 14 cyclopentane derivatives

Detailed assignments of ¹H and ¹³C NMR spectral data for 14 cyclopentane derivatives are reported. The assignments are based on 1D ¹H and ¹³C NMR and on 2D shift‐correlated [¹H, ¹³C‐HMQC], J‐resolved and NOEDIF experiments. Copyright © 2003 John Wiley & Sons, Ltd.     

Stereospecificity of 1H, 13C and 15N shielding constants in the isomers of methylglyoxal bisdimethylhydrazone: problem with configurational assignment based on 1H chemical shifts

In the ¹³C NMR spectra of methylglyoxal bisdimethylhydrazone, the ¹³C‐5 signal is shifted to higher frequencies, while the ¹³C‐6 signal is shifted to lower frequencies on going from the EE to ZE isomer following the trend found previously. Surprisingly, the ¹H‐6 chemical shift and ¹J(C‐6,H‐6) coupling constant are noticeably larger in the ZE isomer than in the EE isomer, although the configuration around the –CH═N– bond does not change. This paradox can be rationalized by the C–H?N intramolecular hydrogen bond in the ZE isomer, which is found from the quantum‐chemical calculations including Bader's quantum theory of atoms in molecules analysis. This hydrogen bond results in the increase of δ(¹H‐6) and ¹J(C‐6,H‐6) parameters. The effect of the C–H?N hydrogen bond on the ¹H shielding and one‐bond ¹³C–¹H coupling complicates the configurational assignment of the considered compound because of these spectral parameters. The ¹H, ¹³C and ¹⁵N chemical shifts of the 2‐ and 8‐(CH₃)₂N groups attached to the –C(CH₃)═N– and –CH═N– moieties, respectively, reveal pronounced difference. The ab initio calculations show that the 8‐(CH₃)₂N group conjugate effectively with the π‐framework, and the 2‐(CH₃)₂N group twisted out from the plane of the backbone and loses conjugation. As a result, the degree of charge transfer from the N‐2– and N‐8– nitrogen lone pairs to the π‐framework varies, which affects the ¹H, ¹³C and ¹⁵N shieldings. Copyright © 2012 John Wiley & Sons, Ltd.     

Substituent Effects on π‐Bond Delocalization of Fulvenes and Fulvalenes. Are Fulvenes Aromatic?

The influence of exocyclic substituents on π‐delocalization of pentafulvenes 2 , heptafulvenes 3 , and nonafulvenes 4 has been investigated. Pentafulvenes 2 : Changes of bond lengths (induced by exocyclic substituents R¹ and R² of 2 ) are reflected by systematic changes of ³J(H,H) (Fig. 2) as well as of ¹J(C,C) coupling constants (Fig. 4), so that linear correlations of σ_p⁺ vs. ³J(H,H) and ¹J(C,C) coupling constants were obtained. Plots of that type are very useful for determining the extent of π‐delocalization of various pentafulvalenes 5 – 8 (Figs. 6 and 12). Charge density effects of pentafulvenes and pentafulvalenes were observed by substituent‐induced shifts of the ring C‐atoms (Fig. 5). Heptafulvenes 3 : Contrary to planar pentafulvenes, heptafulvenes did not show any linear correlations of σ_p⁺ vs. ³J(H,H)‐plots (Fig. 8) or σ_p⁺ vs. δ(¹³C)‐plots (Fig. 9), although substituents R¹, R² clearly influenced ³J(H,H)‐coupling constants as well as ¹³C chemical shifts of the ring H‐atoms and ring C‐atoms. In the NMR spectra of ‘heptafulvenes with inverse ring polarization’ (in the lower range of Fig. 8), ³J(H,H)‐coupling constants were strongly alternating and were barely influenced by exocyclic substituents. This supported a boat conformation of the corresponding heptafulvenes. In the range of Hammett σ_p⁺‐values above ?0.5 to 0, strong substituent effects started to be effective, and a nearly linear approach of ³J(H,H)‐coupling constants J(2,3)/J(4,5) and J(3,4) was observed. This meant that, as soon as heptafulvenes were planar or nearly planar, there existed similar substituent effects as for planar pentafulvenes. – A similar ‘turning point’ was observed in plots of σ_p⁺ vs. ¹³C‐chemical shifts around σ_p⁺=0 (Fig. 9): In the range of strong electron‐accepting groups (above σ_p⁺=1), there was a marked substituent‐induced high‐frequency shift which strongly decreased in the series C(7)>C(2)/C(5)>C(3)/C(4), while C(1)/C(6) was barely influenced. Nonafulvenes 4 : Most nonafulvenes are non‐planar olefins with strongly alternating vicinal H,H‐coupling constants. This has been convincingly shown by the high‐resolution ¹H‐NMR spectrum of 10‐dimethylaminononafulvene ( 4c , Fig. 10), which was not planar but contained a nearly planar (E)‐dienamine substructure of the segment C(7)?C(8)? C(9)?C(10)? NMe₂ according to the NMR data. Only with very strong π‐donors (like two dimethylamino groups in 4b ), planarization of the nine‐membered ring could be observed at low temperatures (Fig. 10). Finally, the first stable nonatriafulvalene (11,12‐bis(diethylamino)nonatriafulvalene ( 10 )) existed in the planar dipolar form in the whole temperature range and even in unpolar solvents.     

Disentangling Complex Mixtures of Compounds with Near‐Identical 1H and 13C NMR Spectra using Pure Shift NMR Spectroscopy

The thorough analysis of highly complex NMR spectra using pure shift NMR experiments is described. The enhanced spectral resolution obtained from modern 2D HOBS experiments incorporating spectral aliasing in the ¹³C indirect dimension enables the distinction of similar compounds exhibiting near‐identical ¹H and ¹³C NMR spectra. It is shown that a complete set of extremely small Δδ(¹H) and Δδ(¹³C) values, even below the natural line width (1 and 5 ppb, respectively), can be simultaneously determined and assigned.     

Complete assignment of NMR data of 22 phenyl‐1H‐pyrazoles' derivatives

Complete assignment of ¹H and ¹³C NMR chemical shifts and J(¹H/¹H and ¹H/¹⁹F) coupling constants for 22 1‐phenyl‐1H‐pyrazoles' derivates were performed using the concerted application of ¹H 1D and ¹H, ¹³C 2D gs‐HSQC and gs‐HMBC experiments. All 1‐phenyl‐1H‐pyrazoles' derivatives were synthesized as described by Finar and co‐workers. The formylated 1‐phenyl‐1H‐pyrazoles' derivatives were performed under Duff's conditions. Copyright © 2011 John Wiley & Sons, Ltd.     

PSYCHE CPMG–HSQMBC: An NMR Spectroscopic Method for Precise and Simple Measurement of Long‐Range Heteronuclear Coupling Constants

Among the NMR spectroscopic parameters, long‐range heteronuclear coupling constants convey invaluable information on torsion angles relevant to glycosidic linkages of carbohydrates. A broadband homonuclear decoupled PSYCHE CPMG–HSQMBC method for the precise and direct measurement of multiple‐bond heteronuclear couplings is presented. The PSYCHE scheme built into the pulse sequence efficiently eliminates unwanted proton–proton splittings from the heteronuclear multiplets so that the desired heteronuclear couplings can be determined simply by measuring frequency differences between peak maxima of pure antiphase doublets. Moreover, PSYCHE CPMG–HSQMBC can provide significant improvement in sensitivity as compared to an earlier Zangger–Sterk‐based method. Applications of the proposed pulse sequence are demonstrated for the extraction of ⁿJ(¹H,⁷⁷Se) and ⁿJ(¹H,¹³C) values, respectively, in carbohydrates; further extensions can be envisioned in any J‐based structural and conformational studies.     

Complete NMR assignment of retinal and its related compounds

Complete and unambiguous ¹H and ¹³C NMR chemical shift assignments for all‐trans‐retinal, 13‐cis‐retinal, 11‐cis‐retinal and 9‐cis‐retinal (1–4) have been established by means of two‐dimensional COSY, HSQC, HMBC and NOESY spectroscopic experiments. Copyright © 2013 John Wiley & Sons, Ltd.     

NMR studies on 1,2‐dihydro‐2‐(4‐aminophenyl)‐4‐[4‐(4‐aminophenoxy)‐4‐phenyl]‐(2H)phthalazin‐1‐one

An unsymmetrical heterocyclic diamine, 1,2‐dihydro‐2‐(4‐aminophenyl)‐4‐[4‐(4‐aminophenoxy)‐4‐phenyl]‐(2H)phthalazin‐1‐one, was synthesized. Its ¹H and ¹³C NMR spectra were completely assigned by utilizing the two‐dimensional heteronuclear ¹³C–¹H multiple‐bond coherence (HMBC) spectroscopy, and heteronuclear ¹³C–¹H one‐bond correlation spectroscopy, homonuclear shift correlation spectroscopy (H,H‐COSY) and rotating frame Overhauser enhancement spectroscopy (ROESY). The structure of the compound was shown to be the phthalazinone rather than the phthalazine ether from cross peaks and chemical shifts of the protons. Copyright © 2002 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.     

A new technique for differentiating between 2J(C,H) and 3/4J(C,H) connectivities

We present a new pulse sequence that yields two simultaneously detected types of long‐range correlation spectra. The one spectrum is to show all ⁿJ(C,H) connectivities and the other is to show exclusively ²J(C,H) connectivities. The method is demonstrated by using strychnine as a test sample. A comparison with HMBC shows that the ²J(C,H)/ⁿJ(C,H) experiment supplies a ⁿJ(C,H) spectrum that is of equal standard with regard to sensitivity and spectral information. The additional ²J(C,H) spectrum allows the disentanglement of ²J(C,H) and ⁿJ(C,H) signals (n > 2) in HMBC type spectra, which greatly simplifies signal assignment and structure elucidation in general. Copyright © 2003 John Wiley & Sons, Ltd.     

Precise Measurement of Long‐Range Heteronuclear Coupling Constants by a Novel Broadband Proton–Proton‐Decoupled CPMG‐HSQMBC Method

A broadband proton–proton‐decoupled CPMG‐HSQMBC method for the precise and direct measurement of long‐range heteronuclear coupling constants is presented. The Zangger–Sterk‐based homodecoupling scheme reported herein efficiently removes unwanted proton–proton splittings from the heteronuclear multiplets, so that the desired heteronuclear couplings can be determined simply by measuring frequency differences between singlet maxima in the resulting spectra. The proposed pseudo‐1D/2D pulse sequences were tested on nucleotides, a metal complex incorporating P heterocycles, and diglycosyl (di)selenides, as well as on other carbohydrate derivatives, for the extraction of ⁿJ(¹H,³¹P), ⁿJ(¹H,⁷⁷Se), and ⁿJ(¹H,¹³C) values, respectively.     

Hydroacridines: Part 23. 1H and 13C NMR spectra of sym‐octahydroacridine,its 9‐(3‐pyridyl) and 9‐(4‐pyridyl) derivatives and the corresponding N(10)‐oxides. An experimental approach to the diamagnetic anisotropy of the pyridine nucleus

The complete ¹H NMR chemical shift assignments of 1,2,3,4,5,6,7,8‐octahydroacridine ( 1 ), 1,2,3,4,5,6,7,8‐octahydro‐9‐(3‐pyridyl)acridine ( 2 ), 1,2,3,4,5,6,7,8‐octahydro‐9‐(4‐pyridyl)acridine ( 3 ) and the corresponding N(10)‐oxides 1a , 2a and 3a , respectively, were achieved on the basis of 400 MHz ¹H NMR spectra and proton–proton decoupling, HMQC and NOEDIFF experiments. The spectral data for the above compounds provided the first experimental evidence of the difference in the anisotropy effect of the two non‐symmetrical moieties of the pyridine nucleus, and allowed us to ascertain that the shielding effect of the moiety defined by the C(2′)—N—C(6′) atoms is weaker than that of the C(3′)—C(4′)—C(5′) moiety. The ¹³C NMR spectra of 1 – 3 and 1a – 3a and the effect of N(10)‐oxidation on the ¹³C NMR chemical shifts are also discussed. The N‐oxidation of 2 and 3 with m‐chloroperbenzoic acid occurred regiospecifically, affording the N(10)‐oxides 2a and 3a free of N(1′)‐oxide isomers. Copyright © 2002 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.     

1,2‐, 1,7‐ and 1,12‐Dicarba‐closo‐dodecaborane(12) Derivatives Revisited by 13C NMR Spectroscopy and DFT Calculations. First Observation of Isotope‐Induced Chemical Shifts 1Δ10/11B(13C), and the Signs and Magnitudes of Coupling Constants 1J(13C,13C) and 1J(13C,11B)

The origin of broadening of ¹³C(carborane) NMR signals of 1,2‐, 1,7‐ and 1,12‐dicarba‐closo‐dodecaboranes(12) and several diphenylsilyl derivatives has been examined in detail and could be traced only partially to unresolved ¹³C–¹¹B spin‐spin coupling. Other contributions to the line widths arise from ¹³C–¹H dipole‐dipole interactions and, in particular, from isotope‐induced chemical shifts ¹Δ^10/11B(¹³C), observed here for carboranes for the first time. In the case of 1‐diphenylsilyl‐1,2‐dicarba‐closo‐dodecaborane(12), the coupling constant ¹J(¹³C,¹³C) = 9.3 Hz was measured in natural abundance of ¹³C. The small value of this coupling constant and its negative sign is predicted by calculations based on optimised structures [B3LYP/6‐311+G(d,p) level of theory] of the parent carboranes and 1‐silyl‐1,2‐dicarba‐closo‐dodecaborane(12) as a model compound [calcd. ¹J(¹³C,¹³C) = –10.5 Hz]. Calculated coupling constants ¹J(¹³C,¹¹B) are small (<7 Hz), in contrast to published assumptions, and of either sign, whereas ¹J(¹¹B,¹¹B) are all positive and range up to 15 Hz.