The first automated 470.59 MHz 19F NMR‐controlled titration: dissociation constants and ion‐specific chemical shifts of 2‐amino‐4‐fluoro 2‐methylpent‐4‐enoic acid

2‐Amino‐4‐fluoro‐2‐methylpent‐4‐enoic acid, obtained as a 1 : 1 salt with trifluoro‐acetic acid, was characterized by ¹H and ¹⁹F high‐resolution NMR spectroscopy. High‐precision potentiometry led to the dissociation constants pK = 1.879 and pK = 9.054. The first automated 470.59 MHz ¹⁹F NMR‐controlled titration yielded the dynamic chemical shift 〈δ_F〉 as a function of pcH or τ and the ion‐specific chemical shifts: δ_F(H₂L⁺) = ?94.81 ppm, δ_F(HL) = ?94.21 ppm, δ_F(L^?) = ?92.45 ppm. The deprotonation gradients were found to be Δ₁ = ?0.60 ppm and Δ₂ = ?1.76 ppm. Copyright © 2002 John Wiley & Sons, Ltd.     

Comparison of the substituent effects on the 13C NMR with the 1H NMR chemical shifts of CHN in substituted benzylideneanilines

Fifty‐two samples of substituted benzylideneanilines XPhCH?NPhYs (XBAYs) were synthesized, and their NMR spectra were determined in this paper. Together with the NMR data of other 77 samples of XBAYs quoted from literatures, the ¹H NMR chemical shifts (δ_H(CH?N)) and ¹³C NMR chemical shifts (δ_C(CH?N)) of the CH?N bridging group were investigated for total of 129 samples of XBAYs. The result shows that the δ_H(CH?N) and δ_C(CH?N) have no distinctive linear relationship, which is contrary to the theoretical thought that declared the δ_H(CH?N) values would increase as the δ_C(CH?N) values increase. With the in‐depth analysis, we found that the effects of σ_F and σ_R of X/Y group on the δ_H(CH?N) and the δ_C(CH?N) are opposite; the effects of the substituent specific cross‐interaction effect between X and Y (Δσ²) on the δ_H(CH?N) and the δ_C(CH?N) are different; the contributions of parameters in the regression equations of the δ_H(CH?N) and the δ_C(CH?N) [Eqns 4 and 7), respectively] also have an obvious difference. Copyright © 2015 John Wiley & Sons, Ltd.     

1H and 13C chemical shifts for acridines: Part XVII. (1,3‐Benzothiazol‐2‐yl)amino‐9(10H)‐acridinone derivatives

The ¹H and ¹³C NMR resonances for 16 acridin‐9(10H)‐ones substituted with amino or (1,3‐benzothiazol‐2‐yl)amino groups were completely and unequivocally assigned by the concerted application of gs‐COSY, gs‐HMQC and gs‐HMBC experiments. Evidence for hydrogen bond and amino–imino tautomerism is presented for 1‐ and 4‐substituted acridin‐9(10H)‐ones. 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.     

Lanthanide‐induced shifts in the structural elucidation of β‐hydroxydecalones

The use of Eu(fod)₃ in the analysis of the ¹H and ¹³C NMR spectra of cis and trans‐fused β‐hydroxydecalones is described. The relative configuration of the substituents is discussed using the PMLIS algorithm to determine the lanthanide (Eu) ion position in the complex in an effective axially symmetric model. The conformations of two cis‐decalones are also discussed. Copyright © 2002 John Wiley & Sons, Ltd.     

Characterization of 2,5‐diaryl‐1,3,4‐oxadiazolines by multinuclear magnetic resonance and density functional theory calculations. Investigation on a case of very remote Hammett correlation

Two series of 2,5‐diaryl‐1,3,4‐oxadiazolines have been studied by multinuclear magnetic resonance and density functional theory calculations. A full NMR spectroscopic characterization has been performed and excellent remote Hammett correlations (σ_p or ) have been found for para substitution in the two aryl rings through at least 11 bonds, notwithstanding the presence in the path of atoms that should act as insulators and a lack of correlation for some of the intermediate atoms. The computational investigation on the electronic delocalization, performed with the ACID (anisotropy of the induced current density) method, reveals indeed that electrons are delocalized in almost the entire molecule despite the presence of the insulators. Copyright © 2009 John Wiley & Sons, Ltd.     

Computation and analysis of 19F substituent chemical shifts of some bridgehead‐substituted polycyclic alkyl fluorides

The ¹⁹F NMR shieldings for several remotely substituted rigid polycyclic alkyl fluorides with common sets of substituents covering a wide range of electronic effects were calculated using the DFT‐GIAO theoretical model. The level of theory, B3LYP/6–311+G(2d,p), was chosen based on trial calculations which gave good agreement with experimental values where known. The optimized geometries were used to obtain various molecular parameters (fluorine natural charges, electron occupancies on fluorine of lone pairs and of the C? F bond, and hybridization states) by means of natural bond orbital (NBO) analysis which could help in understanding electronic transmission mechanisms underlying ¹⁹F substituent chemical shifts (SCS) in these systems. Linear regression analysis was employed to explore the relationship between the calculated ¹⁹F SCS and polar substituent constants and also the NBO derived molecular parameters. The ¹⁹F SCS are best described by an electronegativity parameter. The most pertinent molecular parameters appear to be the occupation number of the NBO p‐type fluorine lone pair and the occupation number of the C? F antibonding orbital. This trend suggests that in these types of rigid saturated systems hyperconjugative interactions play a key role in determining the ¹⁹F SCS. Electrostatic field effects appear to be relatively unimportant. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis and characterization of 1‐ and 2‐cinnamoyloxyacetonaphthones

The synthesis of 1‐ and 2‐cinnamoyloxyacetonaphthones was achieved in one step using hydroxyl acetonaphthones and substituted cinnamic acids in the presence of a catalytic amount of phosphoroxychloride. Structural characterization was accomplished using high‐resolution nuclear magnetic resonance (NMR) spectroscopy. Chemical shifts of the compounds were compared and the change in the chemical shifts relative to electron‐donating and ‐withdrawing groups is presented. Introduction of a thiophene ring instead of phenyl‐substituted analogs caused shielding of the olefinic proton. Copyright © 2010 John Wiley & Sons, Ltd.     

Effect of pH on the rotational conformations of 1,3‐diamino‐2‐hydroxypropane

The effect of pH on the rotational conformations of 1,3‐diamino‐2‐hydroxypropane in aqueous solution was investigated by proton NMR. Both the observed chemical shifts and coupling constants were used to calculate experimental pK_a values. The observed couplings were correlated with the expected couplings for the various possible staggered conformations to try to determine the pattern of conformations for the diamine and its conjugate acids. The best fits suggested a modest preference for the gauche–gauche conformation, especially at low pH, where the diprotonated hydroxydiamine predominates. In methanol, dimethyl sulfoxide and trichloromethane solutions, it was only possible to evaluate the conformational equilibria of the diamine. Slow proton exchange, which caused uncertainties in both chemical shifts and couplings for the monoprotonated and unprotonated diamine, nullified efforts to determine whether or not hydrogen bonding was important for these species in less polar solvents. Copyright © 2002 John Wiley & Sons, Ltd.     

The effect of solvent accessible surface on Hammett‐type dependencies of infinite dilution 29Si and 13C NMR shifts in ring substituted silylated phenols dissolved in chloroform and acetone

Infinite dilution ²⁹Si and ¹³C NMR chemical shifts were determined from concentration dependencies of the shifts in dilute chloroform and acetone solutions of para substituted O‐silylated phenols, 4‐R‐C₆H₄‐O‐SiR′₂R″ (R = Me, MeO, H, F, Cl, NMe₂, NH₂, and CF₃), where the silyl part included groups of different sizes: dimethylsilyl (R′ = Me, R″ = H), trimethylsilyl (R′ = R″ = Me), tert‐butyldimethylsilyl (R′ = Me, R″ = CMe₃), and tert‐butyldiphenylsilyl (R′ = C₆H₅, R″ = CMe₃). Dependencies of silicon and C‐1 carbon chemical shifts on Hammett substituent constants are discussed. It is shown that the substituent sensitivity of these chemical shifts is reduced by association with chloroform, the reduction being proportional to the solvent accessible surface of the oxygen atom in the Si‐O‐C link. Copyright © 2012 John Wiley & Sons, Ltd.     

Hammett MSP and Taft DSP analysis of substituent effects on Mulliken charges of 1‐(arylmethylene)‐1H‐cyclopropanaphthalene

Density functional theory (DFT) method is used to investigate the effects of a variety of substituents (N(CH₃)_2, OCH_3, CH₃,Br, H, F, CN, and NO₂) on Mulliken charge (Q_M) for C‐α and C‐β of 1‐(Arylmethylene)‐1H‐cyclopropanaphthalene using Hammett's mono substituent parameter (MSP) and Taft's dual substituent parameter (DSP) models. The Hammett's model approach gave statistically more significant results than the Taft's model for both carbons atoms. For the C‐α atom a reverse substituent effect was observed and attributed to localized π‐polarization. On the other hand, the MSP and DSP for the C‐β atom showed normal substituent effect. The λ value at the C‐α, explain that the resonance effects more contribution than inductive effects. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2007     

Complete assignment of 1H and 13C NMR spectra of α‐phenylsulfinyl‐N‐methoxy‐ N‐methylpropionamide and some p‐substituted derivatives

The complete assignment of the ¹H and ¹³C NMR spectra of the diastereomeric pairs of some α‐arylsulfinyl‐substituted N‐methoxy‐N‐methylpropionamides with the substituents methoxy, methyl, chloro, nitro is reported. Copyright © 2008 John Wiley & Sons, Ltd.     

1H and 13C NMR analysis of 2‐acetamido‐3‐mercapto‐3‐methyl‐N‐aryl‐butanamides and 2‐acetamido‐3‐methyl‐3‐nitrososulfanyl‐N‐aryl‐butanamide derivatives

The complete assignment of the ¹H and ¹³C NMR spectra of various 2‐acetamido‐3‐mercapto‐3‐methyl‐N‐aryl‐butanamides and 2‐acetamide‐3‐methyl‐3‐nitrososulfanyl‐N‐aryl‐butanamides with p‐methoxy, o‐chloro and m‐chloro substituents is reported. Copyright © 2013 John Wiley & Sons, Ltd.     

Accurate calculation of N1s and C1s core electron binding energies of substituted pyridines. Correlation with basicity and with Hammett substituent constants

Substituent shifts of the energetics of four related ionization processes of pyridines and benzoic acids (Fig. 1) were investigated. The first process is core-electron ionization of gas-phase pyridines (Fig. 1A), while the second concerns gas-phase acid-base reaction between a substituted pyridine and a conjugated acid (Fig. 1B), and the third and fourth processes are the acid dissociation of substituted benzoic acids in aqueous solution (Fig. 1C) and in vacuum (Fig. 1D), respectively. Core-electron binding energies for the first process were calculated using density-functional theory with the scheme ΔE_KS (PW86x-PW91c/TZP+C_rel)//HF/6-31G*. Average absolute deviation of calculated core electron binding energy shifts at N atom in substituted pyridines from experiment was 0.08 eV. The shift at N coincides highly with that at a ring carbon atom. The four shifts corresponding to the four processes shown in Figs. 1A–D correlate strongly with one another, with numerical values fairly close to each other when expressed in unit of electron volts.     

Pd‐Catalyzed Carbonylative α‐Arylation of Aryl Bromides: Scope and Mechanistic Studies

Reaction conditions for the three‐component synthesis of aryl 1,3‐diketones are reported applying the palladium‐catalyzed carbonylative α‐arylation of ketones with aryl bromides. The optimal conditions were found by using a catalytic system derived from [Pd(dba)₂] (dba=dibenzylideneacetone) as the palladium source and 1,3‐bis(diphenylphosphino)propane (DPPP) as the bidentate ligand. These transformations were run in the two‐chamber reactor, COware, applying only 1.5 equivalents of carbon monoxide generated from the CO‐releasing compound, 9‐methylfluorene‐9‐carbonyl chloride (COgen). The methodology proved adaptable to a wide variety of aryl and heteroaryl bromides leading to a diverse range of aryl 1,3‐diketones. A mechanistic investigation of this transformation relying on ³¹P and ¹³C NMR spectroscopy was undertaken to determine the possible catalytic pathway. Our results revealed that the combination of [Pd(dba)₂] and DPPP was only reactive towards 4‐bromoanisole in the presence of the sodium enolate of propiophenone suggesting that a [Pd(dppp)(enolate)] anion was initially generated before the oxidative‐addition step. Subsequent CO insertion into an [Pd(Ar)(dppp)(enolate)] species provided the 1,3‐diketone. These results indicate that a catalytic cycle, different from the classical carbonylation mechanism proposed by Heck, is operating. To investigate the effect of the dba ligand, the Pd⁰ precursor, [Pd(η³‐1‐PhC₃H₄)(η⁵‐C₅H₅)], was examined. In the presence of DPPP, and in contrast to [Pd(dba)₂], its oxidative addition with 4‐bromoanisole occurred smoothly providing the [PdBr(Ar)(dppp)] complex. After treatment with CO, the acyl complex [Pd(CO)Br(Ar)(dppp)] was generated, however, its treatment with the sodium enolate led exclusively to the acylated enol in high yield. Nevertheless, the carbonylative α‐arylation of 4‐bromoanisole with either catalytic or stoichiometric [Pd(η³‐1‐PhC₃H₄)(η⁵‐C₅H₅)] over a short reaction time, led to the 1,3‐diketone product. Because none of the acylated enol was detected, this implied that a similar mechanistic pathway is operating as that observed for the same transformation with [Pd(dba)₂] as the Pd source.     

DFT‐GIAO 1H and 13C NMR prediction of chemical shifts for the configurational assignment of 6β‐hydroxyhyoscyamine diastereoisomers

¹H and ¹³C NMR chemical shift calculations using the density functional theory–gauge including/invariant atomic orbitals (DFT–GIAO) approximation at the B3LYP/6‐311G++(d,p) level of theory have been used to assign both natural diastereoisomers of 6β‐hydroxyhyoscyamine. The theoretical chemical shifts of the ¹H and ¹³C atoms in both isomers were calculated using a previously determined conformational distribution, and the theoretical and experimental values were cross‐compared. For protons, the obtained average absolute differences and root mean square (rms) errors for each comparison showed that the experimental chemical shifts of dextrorotatory and levorotatory 6β‐hydroxyhyoscyamines correlated well with the theoretical values calculated for the (3R,6R,2′S) and (3S,6S,2′S) configurations, respectively, whereas for ¹³C atoms the calculations were unable to differentiate between isomers. The nature of the relatively large chemical shift differences observed in nuclei that share similar chemical environments between isomers was asserted from the same calculations. It is shown that the anisotropic effect of the phenyl group in the tropic ester moiety, positioned under the tropane ring, has a larger shielding effect over one ring side than over the other one. Copyright © 2009 John Wiley & Sons, Ltd.     

1H and 13C chemical shifts for acridines: Part XVIII. 9‐Chloroacridine and 9‐(N‐allyl)‐ and 9‐(N‐propargyl)acridinamine derivatives

The¹H and ¹³C NMR resonances for acridine derivatives 9‐substituted with chloro, allylamino and propargylamino groups were completely assigned using a concerted application of gs‐COSY, gs‐HMQC and gs‐HMBC experiments. 9‐(N‐Allyl)‐ and 9‐(N‐propargyl)acridinamine derivatives present amino–imino tautomerism including a large broadening of ¹H and ¹³C NMR signals at room temperature. To obtain suitable resolution, therefore, these latter compounds were studied at 370 K in DMSO‐d6 solutions and showed a complete shift towards the imino tautomers. Copyright © 2003 John Wiley & Sons, Ltd.     

Torsion angle relationship of the 17O NMR chemical shift in α,β‐unsaturated carbonyl compounds

The torsion angle effect on the isotropic shielding of ¹⁷O nucleus in α,β‐unsaturated carbonyl groups is studied by means of density functional theory (DFT) calculations using a polarizable continuum model (PCM) for the solvent, employing the PBE0 functional together with the 6‐311G(d,p) basis set for geometry optimization, and the 6‐311+G(2d,p) basis set for calculating the NMR shielding with the gauge‐including atomic orbitals (GIAO) method. This study adds new information on the sensitivity of the ¹⁷O nucleus to conformational changes, revealing a strong dependence of the ¹⁷O NMR chemical shift on the dihedral angle between the carbonyl and the vinyl moiety in all studied compounds; remarkable differences are observed with the data reported for α‐diketones. Copyright © 2009 John Wiley & Sons, Ltd.     

Complete NMR assignment of (+)‐10β,14‐dihydroxy‐allo‐aromadendrane

The assignment of ¹H and ¹³C NMR of the sesquiterpene (+)‐10β,14‐dihydroxy‐allo‐aromadendrane by means of two‐dimensional NMR is reported. Copyright © 2003 John Wiley & Sons, Ltd.