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.     

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.     

Synthesis of rhodium(III) complexes with tris/tetrakis‐benzimidazoles and benzothiazoles—quick identification of cyclometallation by nuclear magnetic resonance spectroscopy

Reactions of rhodium(III) halides with multidentate N,S‐heterocycles, (LH₃) 1,3,5‐tris(benzimidazolyl)benzene (L¹H₃; 1 ), 1,3,5‐tris(N‐methylbenzimidazolyl) benzene (L²H₃; 2 ) and 1,3,5‐tris(benzothiazolyl)benzene (L³H₃; 3 ), in the molar ratio 1:1 in methanol–chloroform produced mononuclear cyclometallated products of the composition [RhX₂(LH₂)(H₂O)] (X = Cl, Br, I; LH₂ = L¹H₂, L²H₂, L³H₂). When the metal to ligand ( 1–3 or 1,2,4,5‐tetrakis(benzothiazolyl)benzene [L⁴H₂; 4 ]) molar ratio was 2:1, the reactions yielded binuclear complexes of the compositions [Rh₂Cl₅(LH₂)(H₂O)₃] (LH₂ = L¹H₂, L²H₂, L³H₂) and [Rh₂X₄(L⁴)(H₂O)₂] (X = Cl, Br, I). Elemental analysis, IR and ¹H nuclear magnetic resonance (NMR) chemical shifts supported the binuclear nature of the complexes. Cyclometallation was detected by conventional ¹³C NMR spectra that showed a doublet around ～190 ppm. Cyclometallation was also detected by gradient‐enhanced heteronuclear multiple bond correlation (g‐HMBC) experiment that showed cross‐peaks between the cyclometallated carbon and the central benzene ring protons of 1–3 . Cyclometallation was substantiated by two‐dimensional ¹H? ¹H correlated experiments (gradiant‐correlation spectroscopy and rotating frame Overhauser effect spectroscopy) and ¹H? ¹³C single bond correlated two‐dimensional NMR experiments (gradient‐enhanced heteronuclear single quantum coherence). The ¹H? ¹⁵N g‐HMBC experiment suggested the coordination of the heterocycles to the metal ion via tertiary nitrogen. Copyright © 2009 John Wiley & Sons, Ltd.     

Investigation of the correlations between 19F and 1H NMR signals for various mono‐ and di‐substituted octafluoro[2.2]paracyclophanes

A selection of mono‐ and pseudo ortho di‐substituted octafluoro[2.2]paracyclophane derivatives were analyzed using ¹⁹F‐¹H HOESY, ¹H COSY and ¹⁹F COSY techniques. This resulted in the unambiguous assignment of the ¹⁹F and ¹H NMR resonances, and also revealed interesting solvent effects and noteworthy coupling patterns for various J_HH, J_HF, and J_FF interactions, including observable through bond ⁷J_FF and ⁸J_FF couplings. For the four mono‐substituted derivatives, the assignments were achieved through the combination of ¹⁹F‐¹H HOESY, ¹H COSY and ¹⁹F COSY techniques. The C₂ symmetry of the six pseudo ortho di‐substituted derivatives that were examined produced simplified spectra, and careful inspection of the characteristic ¹H coupling patterns led to the assignment of ¹H signals. Therefore only ¹⁹F‐¹H HOESY experiments were required to complete the assignments for those molecules. Refinements and alternative strategies for previous protocols are presented for the molecules that were less responsive to nuclear Overhauser effect (nOe) experiments. Copyright © 2009 John Wiley & Sons, Ltd.     

The microstructure determination of ethylene‐styrene‐propylene terpolymers at triad level by high‐temperature two‐dimensional NMR spectra

To further extend temperature range of application and low temperature performance of the ethylene‐styrene copolymers, a series of poly(ethylene‐styrene‐propylene) samples with varying monomer compositions and relatively low glass‐transition temperatures (T_g = −28 – 22 °C) were synthesized by Me₂Si(Me₄Cp)(N‐t‐Bu)TiCl2/MMAO system. Since the ¹³C NMR spectra of the terpolymers were complex and some new resonances were present, 2D‐¹H/¹³C heteronuclear single quantum coherence and heteronuclear multiple bond correlation experiments were conducted. A complete ¹³C NMR characterization of these terpolymers was performed qualitatively and quantitatively, including chemical shifts, triad sequence distributions, and monomer average sequence lengths. © 2017 Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018 , 56, 340–350     

Isolation and spectral study of 4‐methyl‐6,8‐dihydroxy‐7H‐benz[de]anthracen‐7‐one

4‐Methyl‐6,8‐dihydroxy‐7H‐benz[de]anthracen‐7‐one was isolated from the sap of Aloe by column chromatography. Its ¹H and ¹³C NMR spectra were completely assigned by utilizing two‐dimensional ¹H‐detected heteronuclear one‐bond (HMQC) and multiple‐bond (HMBC) chemical shift correlation experiments together with ¹H–¹H COSY and DEPT techniques. These techniques were also valuable in assigning the protons and carbons of those benzanthrone compounds which were previously incompletely reported because of the overlap of proton signals. The molecular structure was elucidated by 2D NMR analysis. The spectral properties (MS, IR and UV) are also presented. Copyright © 2003 John Wiley & Sons, Ltd.     

Long‐range 19F–15N heteronuclear shift correlation: examination of J‐modulations associated with broad range accordion excitation

The first demonstrated example of ¹⁹F–¹⁵N long‐range heteronuclear shift correlation spectroscopy at natural abundance is reported. Because of the very large variation in the size of ²J(N,F) vs ³J(N,F) long‐range heteronuclear couplings, the utilization of one of the new accordion‐optimized long‐range heteronuclear shift correlations experiments is essential if all possible correlations are to be observed in a single experiment. A modified IMPEACH‐MBC pulse sequence was used in conjunction with an optimization range from 4 to 50 Hz to demonstrate the technique using a mixture of 2‐ and 3‐fluoropyridine, which had ²J(N,F) and ³J(N,F) long‐range couplings of ?52 and 3.6 Hz, respectively. Because of the size of the ²J(N,F) long‐range coupling constant, a J‐modulation of the long‐range correlation response is observed in the spectrum resulting in a ‘doublet’ in F₁ due to amplitude modulation. The size of the ‘doublet’ is shown to be a function of the parameter selection (t_1max,T_max,T_min and spectral width in F₁). This behavior is similar to F₁ ‘skew’ associated with long‐range correlation responses in ACCORD‐HMBC spectra which has been analyzed in detail previously. Copyright © 2002 John Wiley & Sons, Ltd.     

Selective J‐resolved HMBC,an efficient method for measuring heteronuclear long‐range coupling constants

An efficient pulse sequence for measuring long‐range C? H coupling constants (J_{C? H}) named selective J‐resolved HMBC has been developed by replacing a ¹H 180° pulse with a selective ¹H 180° pulse and the HMBC pulse scheme with the constant time (CT) HMBC employed in the J‐resolved HMBC pulse sequence that we reported previously. The novel pulse sequence providing only long‐range J_{C? H} cross peaks for easy and accurate analysis enables to overcome disadvantages of the previous HMBC‐based pulse sequences (J‐resolved HMBC‐1) along with maintaining high sensitivity. The efficiency of measuring long‐range J_{C? H} using the proposed pulse sequence has been demonstrated in applications to the complicated natural products, portmicin and monazomycin. Copyright © 2009 John Wiley & Sons, Ltd.     

Structure elucidation of [1,3]oxazolo[4,5‐e][2,1]benzisoxazole and naphtho[1,2‐d][1,3]‐ and phenanthro[9,10‐d]oxazoles using gradient selected gHMBC,gHMQC and gHMQC‐TOCSY NMR techniques

Structure elucidation of compounds in the benzisoxazole series ( 1 – 6 ) and naphtho[1,2‐d][1,3]‐ ( 7 – 10 ) and phenanthro[9,10‐d][1,3]oxazole ( 11 – 14 ) series was accomplished using extensive 2D NMR spectroscopic studies including ¹H–¹H COSY, long‐ range ¹H–¹H COSY, ¹H–¹³C COSY, gHMQC, gHMBC and gHMQC‐TOCSY experiments. The distinction between oxazole and isoxazole rings was made on the basis of the magnitude of heteronuclear one‐bond ¹J_{C2, H2} (or ¹J_{C3, H3}) coupling constants. Complete analysis of the ¹H NMR spectra of 11 – 14 was achieved by iterative calculations. Gradient selected gHMQC‐TOCSY spectra of phenanthro[9,10‐d][1,3]oxazoles 11 – 14 were obtained at different mixing times (12, 24, 36, 48 and 80 ms) to identify the spin system where the protons of phenanthrene ring at H‐5, H‐6 and at H‐9 and H‐7 and H‐8 were highly overlapping. Copyright © 2003 John Wiley & Sons, Ltd.     

One‐ and two‐dimensional NMR characterization of N‐vinyl‐2‐pyrrolidone/methyl acrylate copolymers

N‐vinyl‐2‐pyrrolidone/methyl acrylate (V/M) copolymers were prepared by free‐radical bulk polymerization using benzoyl peroxide as an initiator. The copolymer composition of these copolymers was calculated from ¹H NMR spectra. The radical reactivity ratios for N‐vinyl‐2‐pyrrolidone (V) and methyl acrylate (M) were r_V = 0.09, r_M = 0.44. These reactivity ratios for the copolymerization of V and M were determined using the Kelen–Tudos and nonlinear least‐squares error‐in‐variable methods. The ¹³C{¹H} and ¹H NMR spectra of these copolymers overlapped and were complex. The complete spectral assignment of the ¹³C and ¹H NMR spectra were done with distortionless enhancement by polarization transfer and two dimensional ¹³C‐¹H heteronuclear single quantum correlation spectroscopic experiments. The two‐dimensional ¹H‐¹H homonuclear total correlation spectroscopic NMR spectrum showed the various bond interactions, thus inferring the possible structure of the copolymers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2225–2236, 2002     

One‐ and two‐dimensional NMR characterization of N‐vinyl‐2‐pyrrolidone/methyl acrylate copolymers

N‐vinyl‐2‐pyrrolidone/methyl acrylate (V/M) copolymers were prepared by free‐radical bulk polymerization using benzoyl peroxide as an initiator. The copolymer composition of these copolymers was calculated from ¹H NMR spectra. The radical reactivity ratios for N‐vinyl‐2‐pyrrolidone (V) and methyl acrylate (M) were r_V = 0.09, r_M = 0.44. These reactivity ratios for the copolymerization of V and M were determined using the Kelen–Tudos and nonlinear least‐squares error‐in‐variable methods. The ¹³C{¹H} and ¹H NMR spectra of these copolymers overlapped and were complex. The complete spectral assignment of the ¹³C and ¹H NMR spectra were done with distortionless enhancement by polarization transfer and two dimensional ¹³C‐¹H heteronuclear single quantum correlation spectroscopic experiments. The two‐dimensional ¹H‐¹H homonuclear total correlation spectroscopic NMR spectrum showed the various bond interactions, thus inferring the possible structure of the copolymers. © 2002 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 40: 2225–2236, 2002     

Simplifying LR‐HSQC spectra using a triple‐quantum filter: The LR‐HTQC experiment

Long‐range heteronuclear single quantum correlation (LR‐HSQC) experiments may be applied for detecting long‐range correlations but suffer from two disadvantages, common to all heteronuclear long‐range correlation experiments: (i) The information density in LR‐HSQC spectra may be too high to be used directly without “filtering out” shorter range correlations, and (ii) often, substantial differences in intensity among cross peaks exist, potentially hampering the visualization of weak, often crucial cross peaks. In this contribution, we propose a modified LR‐HSQC experiment, the LR‐HTQC experiment (Long‐Range Heteronuclear Triple Quantum Correlation) that partially solves the problems aforementioned. We show theoretically and experimentally that the LR‐HTQC experiment removes the intense cross peaks of CH spin pairs, substantially reduces the medium intensity of cross peaks originating from CHH' spin systems, whereas the typically weak intensity of cross peaks of CHH'H″ and C(H)_n, _{n > 3} spin systems is less affected. Consequently, the LR‐HTQC experiment affords simplified long‐range heteronuclear shift correlation spectra and scales down large intensity differences among different types of cross peaks, although a certain general reduction of signal intensities has to be accepted.     

NMR study on 9‐S and 9‐R oxirane derivatives of ascomycin

Structure elucidation of 9‐S and 9‐R oxirane derivatives of ascomycin, a 23‐membered immunomodulating macrolactam, was performed using NMR spectroscopy. The total ¹H and ¹³C signal assignments required the gradient‐selected versions of COSY (gs‐COSY), heteronuclear multiple quantum‐correlation spectroscopy (gs‐HSQC), heteronuclear multiple‐bond correlation spectroscopy (gs‐HMBC), and nuclear Overhauser methods. The data sets then were used to examine the dependence of ketone–hemiketal and cis–trans amide equilibria on the substitution pattern and the absolute configuration of the chiral oxirane. Copyright © 2002 John Wiley & Sons, Ltd.     

Comparison of 1H–19F two‐dimensional NMR scalar coupling correlation pulse sequences

The effectiveness of hetero‐COSY, HETCOR, HMQC, and HSQC two‐dimensional NMR pulse sequences for detection of ¹⁹F–¹H correlations by scalar coupling was evaluated on monofluorinated and polyfluorinated test compounds. All four of these sequences were effective in observing ¹H–¹⁹F correlations, using either ¹⁹F or ¹H as the observe nucleus. All four sequences were amenable, to some degree, to adjustment to observe larger or smaller couplings preferentially. A 1/2J echo filter was effectively applied to remove artifacts from ²J_FF strong coupling. The HETCOR experiments afforded the best overall combination of sensitivity, resolution and selectivity for J_HF. Copyright © 2014 John Wiley & Sons, Ltd.     

BASHD‐J‐resolved‐COSY: a new method for measuring proton‐proton spin coupling constants of multiplet signals

An effective pulse sequence for measuring H–H coupling constants, named BASHD‐J‐resolved‐COSY, has been developed. In the spin systems such as –CH_A–CH_B(CH₃)–CH_C–, a methine proton H_B splits into a multiplet owing to several vicinal couplings, resulting in attenuation of its cross‐peak intensity. Therefore, the measurements of ³J_H–H with respect to H_B are generally difficult in the E‐COSY‐type experiments. With the aim of accurate measurements of ³J_H‐H in such a spin system, we have developed a new pulse sequence, which selectively decouples the secondary methyl group. The proposed pulse sequence provides the simplified cross‐peak patterns, which are suitable for reliable measurements of ³J_H‐H in a complicated natural product. Copyright © 2012 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.     

Observation of potentially troublesome 2JCC correlations in 1,1‐ADEQUATE spectra

Despite the tremendous usage of HMBC to establish long‐range ¹H–¹³C and ¹H–¹⁵N heteronuclear correlations, an inherent drawback of the experiment is the indeterminate nature of the ⁿJ_XH correlations afforded by the experiment. A priori there is no reliable way of determining whether a given ⁿJ_CH correlation is, for example, via two‐, three‐, or sometimes even four‐bonds. This limitation of the HMBC experiment spurred the development of the ADEQUATE family of NMR experiments that rely on, in the case of 1,1‐ADEQUATE, an out‐and‐back transfer of magnetization via the ¹J_CC homonuclear coupling constant, which is significantly larger than ⁿJ_CC (where n = 2–4) couplings in most cases. Hence, the 1,1‐ADEQUATE experiment has generally been assumed to unequivocally provide the equivalent of ²J_CH correlations. The recent development of the 1,1‐ and 1,n‐HD‐ADEQUATE experiments that can provide homodecoupling for certain ¹J_CC and ⁿJ_CC correlations has increased the sensitivity of the ADEQUATE experiments significantly and can allow acquisition of these data in a fraction of the time required for the original iterations of this pulse sequence. With these gains in sensitivity, however, there occasionally come unanticipated consequences. We have observed that the collapse of proton multiplets, in addition to providing better s/n for the desired ¹J_CC correlations can facilitate the observation of typically weaker ²J_CC correlations across intervening carbonyl resonances in 1,1‐HD‐ADEQUATE spectra. Several examples are shown, with the results supported by the measurement of the ²J_CC coupling constants in question using J‐modulated‐HD‐ADEQUATE and DFT calculations. Copyright © 2016 John Wiley & Sons, Ltd.     

Heteronuclear NMR Spectroscopy as a Surface‐Selective Technique: A Unique Look at the Hydroxyl Groups of γ‐Alumina.

The surface hydroxyl groups of γ‐alumina dehydroxylated at 500 °C were studied by a combination of one‐ and two‐dimensional homo‐ and heteronuclear ¹H and ²⁷Al NMR spectroscopy at high magnetic field. In particular, by harnessing ¹H–²⁷Al dipolar interactions, a high selectivity was achieved in unveiling the topology of the alumina surface. The terminal versus bridging character of the hydroxyl groups observed in the ¹H magic‐angle spinning (MAS) NMR spectrum was demonstrated thanks to ¹H–²⁷Al RESPDOR (resonance‐echo saturation‐pulse double‐resonance). In a further step the hydroxyl groups were assigned to their aluminium neighbours thanks to a {¹H}‐²⁷Al dipolar heteronuclear multiple quantum correlation (D‐HMQC), which was used to establish a first coordination map. Then, in combination with ¹H–¹H double quantum (DQ) MAS, these elements helped to reveal intimate structural features of the surface hydroxyls. Finally, the nature of a peculiar reactive hydroxyl group was demonstrated following this methodology in the case of CO₂ reactivity with alumina.     

Synthesis and solid‐state structures of t‐Bu3Ga–EPh3 Lewis acid–base adducts

Three Lewis acid–base adducts t‐Bu₃Ga–EPh₃ (E = P 1 , As 2 , Sb 3 ) were synthesized by reactions of Ph₃E and t‐Bu₃Ga and characterized by heteronuclear NMR (¹H, ¹³C (³¹P)) and IR spectroscopy, elemental analysis and single crystal X‐ray diffraction. Their structural parameters are discussed and compared to similar t‐Bu₃Ga adducts. The strength of the donor‐acceptor interactions within 1 – 3 was investigated in solution by temperature‐dependent ¹H NMR spectroscopy and by quantum chemical calculations.     

1H, 13C and 15N NMR spectroscopic,x‐ray structural and ab initio/HF studies on nitramino and N‐alkylamino‐4‐nitro derivatives of pyridine N‐oxides and pyridines

The ¹H, ¹³C and ¹⁵N NMR spectra in DMSO‐d₆ were measured for eight nitraminopyridine N‐oxides, ten 4‐nitropyridine N‐oxides, four 2‐nitraminopyridines and five 4‐nitropyridines. Their chemical shift assignments are based on PFG ¹H,X (X = ¹³C and ¹⁵N) HMQC and HMBC experiments. The relative energies for the tautomers of two nitraminopyridine N‐oxides were determined by ab initio HF/6–311G** calculations. A single‐crystal x‐ray structural analysis was made for 4‐methyl‐2‐nitraminopyridine: C₆H₇O₂N₃, M = 153.15, triclinic, space group P‐1 (No. 2), a = 7.0275(4), b = 6.8034(3), c = 8.6086(5) Å, α = 103.620(2), β = 90.309(2), γ = 122.215(3)°, V = 334.11(3) ų, Z = 2. Copyright © 2003 John Wiley & Sons, Ltd.