Studies on the Stereochemistry of 2-(Nitromethylidene)-Heterocycles

The ¹H-NMR spectra of 2-(nitromethylidene)pyrrolidine ( 7 ), 1-methyl-2-(nitromethylidene)imidazolidind ( 10 ) and 3-(nitromethylidene)tetrahydrothiazine ( 11 ) in CDCl₃ and (CD₃)₂SO indicate that these compounds have the intramolecularly H-bonded structures (Z)- 7 , (E)- 10 and (Z)- 11 while the N-methyl derivative 8 of 7 is (E)-configurated in both solvents. 1-Benzylamino-1-(methyltio)-2-nitroehtylene ( 13 ), an acylic model, has the H-bonded configuration (E)- 13 in CDCl₃ and in (CD₃)₂SO. 2-(Nitromethylidene)thiazolidine ( 3 ) has the (E)-configuration in CDCl₃ but exists in (CD₃)₂SO as a mixture of (Z)- and (E)-isomers with the former predominating. Both species are detected to varying proportions in a mixture of the two solvents. ¹⁵N-NMR spectroscopy of 3 ruled out unambiguously the nitronic acid structure 6 and the nitromethyleimine structure 5 . The N-methyl derivative 4 of 3 is (Z)-configurated in (CD₃)₂SO. Comparison of the olefinic proton shifts of (Z)- 3 and (Z)- 4 with those of analogues and also of 1,1-bis(methylti)-2-nitroethylene ( 12 ) shows decreased conjugation of the lone pair of electrons of the ring N-atom in (Z)- 3 and (Z)- 4 . This is also supported by ¹³C-NMR studies. Plausible explanations for the phenomenon are offered by postulating that the ring N-atoms are pyramidal in (Z)- 3 and (Z)- 4 and planar in other cases or, alternatively, that the conjugated nitroenamine system gets twisted due to steric interaction between the NO₂-group and the ring S-atom. Single-crystal X-ray studies of 3 and 8 show that the former exists in the (Z)-configuration and the latter in (E)-configuration; the ring N-atom in the former has slightly more pyramidal character than in the latter.     

Structure of Cyanoacetylhydrazones of Aldehydes and Ketones

1D ¹H and ^{1 3}C, and 2D ¹H NOESY NMR were used to establish that cyanoacetylhydrazones of aliphatic and aromatic aldehydes and ketones in CDCl₃ and (CD₃)₂SO solutions have a linear structure, exist as a mixture of geometric isomers by the C = N bond, and exhibit hindered amide rotation.     

Etude RMN de β-hydroxy-phosphonates-esters. Détermination du signe du couplage stéréospécifique 4J(P?C?C?O?H) dans le diastéréoisomère RS,RS

INDOR experiments indicate ⁴J(P? C? C? O? H) to be positive for the β-hydroxyphosphonate ester RS,RS dissolved in (CD₃)₂CO or (CD₃)₂SO. The higher value observed in (CD₃)₂SO than in (CD₃)₂CO shows that a W geometry makes this coupling constant more positive.     

The structure of angustifoline,an alkaloid ofLupinus angustifolius,in solution

Summary The¹H and¹³C NMR spectra of the lupin alkaloidangustifoline 1 in four solvents (cyclohexane-d₁₂, CDCl₃, CD₃CN, and C₆D₆) were assigned using 2D H,H and H,C COSY and 2D J-resolved spectra. The torsional HCCH angles calculated from the vicinalJ _HH coupling constants are essentially in agreement with those expected for the deformed all-chair conformation withendo oriented N(12)-H bond, reported earlier for1 in the solid state. Some arguments seem to point, however, to a small contribution of other conformations: with ring A deformed in another direction, deformed all-chair withexo oriented N(12)-H bond and/or a conformation with ring C in the boat form.Lupin Alkaloids, part 7     

A conformational NMR analysis of methymycin aglycones: complete and unambiguous assignments of stereochemically diverse glycosylated methymycin analogs by 1D and 2D NMR techniques and molecular modeling

The ¹H and ¹³C NMR spectra of 10‐deoxymethynolide (1), 8.9‐dihydro‐10‐deoxymethynolide (2) and its glycosylated derivatives (3–9) were analyzed using gradient‐selected NMR techniques, including 1D TOCSY, gCOSY, 1D NOESY (DPFGSENOE), NOESY, gHMBC, gHSQC and gHSQC‐TOCSY. The NMR spectral parameters (chemical shifts and coupling constants) of 1–9 were determined by iterative analysis. For the first time, complete and unambiguous assignment of the ¹H NMR spectrum of 10‐deoxymethynolide (1) has been achieved in CDCl₃, CD₃OD and C₆D₆ solvents. The ¹H NMR spectrum of 8,9‐dihydro‐10‐deoxymethynolide (2) was recorded in CDCl₃, (CD₃)₂CO and CD₃OD solutions to determine the conformation. NMR‐based conformational analysis of 1 and 2 in conjugation with molecular modeling concluded that the 12‐membered ring of the macrolactones may predominantly exist in a single stable conformation in all solvents examined. In all cases, a change in solvent caused only small changes in chemical shifts and coupling constants, suggesting that all glycosylated methymycin analogs exist with similar conformations of the aglycone ring in solution. Copyright © 2013 John Wiley & Sons, Ltd.     

Reaction of Internal Fluoroolefin Oxides with Camphor Thiosemicarbazone

Epoxy derivatives of internal fluoroolefins (both cis and trans isomers) react in a stereospecific manner with (1S)- or rac-camphor thiosemicarbazone in a polar aprotic medium to give the corresponding 5-fluoro-4-hydroxy-4,5-bis(polyfluoroalkyl)thiazol-2-ylhydrazones. From unsymmetrical 2,3-epoxydodecafluorohexane a mixture of regioisomeric hydrazones is formed. According to the ¹H and ^{1 9}F NMR data, the resulting trans-hydrazones in (CD₃)₂SO and CDCl₃ exist as mixtures of diastereoisomers occurring in a dynamic equilibrium.     

A Solvent Switch for the Stabilization of Multiple Hemiacetals on an Inorganic Platform: Role of Supramolecular Interactions

Reaction of Zn(OAc)₂ ? 2 H₂O with 2,6‐diisopropylphenyl phosphate (dippH₂) in the presence of pyridine‐4‐carboxaldehyde (Py‐4‐CHO) in methanol resulted in the isolation of a tetrameric zinc phosphate cluster [Zn(dipp)(Py‐4‐CH(OH)(OMe))]₄ ? 4 MeOH ( 1 ) with four hemiacetal moieties stabilized on the double‐4‐ring inorganic cubane cluster. The change of solvent from methanol to acetonitrile leads to the formation of [Zn(dipp)(Py‐4‐CHO)]₄ ( 2 ), in which the coordinated Py‐4‐CHO retains its aldehydic form. Dissolution of 1 in CD₃CN readily converts it to the aldehydic form and yields 2 . Similarly 2 , which exists in the aldehyde form in CD₃CN, readily converts to the hemiacetal form in CD₃OD/CH₃OH. Compound 1 is an unprecedented example in which four hemiacetals have been stabilized on a single molecule in the solid state retaining its stability in solution as revealed by its ¹H NMR spectrum in CD₃OD. The solution stability of 1 and 2 has further been confirmed by ESI‐MS studies. To generalize the stabilization of multiple hemiacetals on a single double‐four‐ring platform, pyridine‐2‐carboxaldehyde (Py‐2‐CHO) was used as the auxiliary ligand in the reaction between zinc acetate and dippH₂, leading to isolation of [Zn(dipp)(Py‐2‐CH(OH)(OMe))]₄ ( 3 ). Understandably, recrystallization of 3 from acetonitrile yields the parent aldehydic form, [Zn(dipp)(Py‐2‐CHO)]₄ ( 4 ). Single‐crystal X‐ray diffraction studies reveal that supramolecular bonding, aided by hydrogen‐bonding interactions involving the hemiacetal functionalities (C?OH, C?OMe, and C?H), are responsible for the observed stabilization. The hemiacetal/aldehyde groups in 1 and 2 readily react with p‐toluidine, 2,6‐dimethylaniline, and 4‐bromoaniline to yield the corresponding tetra‐Schiff base ligands, [Zn(dipp)(L)]₄ (L=4‐methyl‐N‐(pyridin‐4‐ylmethylidene)aniline ( 5 ), 2,6‐dimethyl‐N‐(pyridin‐4‐ylmethylene)‐aniline ( 6 ), and 4‐bromo‐N‐(pyridin‐4‐ylmethylene)aniline ( 7 )). Isolation of 5 – 7 opens up further possibilities of using 1 and 2 as new supramolecular synthons and ligands.     

Structural studies of flavan derivatives: effect of overcrowding on conformation and hydrogen bonding of cis- and trans-diphenyl flavan-3 yl carbinols

IR, ¹H NMR and X-ray crystallographic studies of the title compounds show that the trans-isomer exhibit a diaxially substituted half-chair conformation of the dihydropyran ring owing to destabilization of the alternative overcrowded diequatorial conformation Steric hindrance prevents a closer approach of the hydroxyl group to the ring oxygen limiting the strength of the OH…O intramolecular hydrogen bonding and allowing thermal vibration of large amplitude. The cis isomer adopts a C(3) sofa conformation for the dihydropyran ring, tightly bonded by a strong OH…π intramolecular hydrogen bonding which contributes to a higher rigidity of the whole molecule.     

Effect of Temperature and Solvent on the Structure of Amide Cavitands

Conformational changes of amide cavitands A – C were investigated at varied temperatures and in several solvents. While cavitands A and B , with comparatively smaller substituents such as Et and ⁱPr, were always in vase conformation in non‐polar solvents such as CDCl₃, CD₂Cl₂, (D₈)THF, and C₆D₆, their thermoswitching (vase to kite) was observed in polar solvents such as (D₇)DMF and (D₆)DMSO or in the presence of acid (TFA) and H‐bonding inhibitor (TFE). Intra‐ and interannular H‐bonds of A and B were clearly observed by low‐temperature ¹H‐NMR spectra in CDCl₃. No conformational change of cavitand C with bigger substituent (^tBu) was observed under any tested temperature range and in polar or non‐polar solvents; C was always in the kite conformation.     

Analogs of Cinchona Alkaloids Incorporating a 9,9′-Spirobifluorene Moiety

The Cinchona alkaloid analogs (+)- and (?)- 5 with a quinuclidine-2-methanol residue attached to C(2) of a 9,9′-spirobifluorene moiety were prepared as a racemic mixture by reacting lithiated 2-bromo-9,9′-spirobifluorene 7 with (2-ethoxycarbonyl)quinuclidine (±)- 6 to give ketone (±)- 8 , followed by diastereoselective reduction with diisobutylaluminum hydride (DIBAL-H). The absolute configuration at C(9) and C(8), i.e., at the methanol bridge and the adjacent quinuclidine C-atom, in the two enantiomers of 5 is identical to the configuration at the corresponding centers in (?)-quinine ( 1 ) and (+)-quinidine ( 2 ), respectively. For the optical resolution of (±)- 5 , a chiral stationary phase for HPLC was prepared by covalently bonding quinine via a thiol spacer to a silica-gel surface. The enantiomer separation was accomplished at an α value of 1.61 with (±)- 5 being eluted last, in agreement with ¹H-NMR studies in CDCl₃ which showed that (+)- 5 underwent a more stable host-guest association with quinine than (?)- 5 . ¹H{¹H} Nuclear Overhauser effect (NOE) difference spectroscopical analysis of the host-guest associations with quinine in CDCl₃, combined with computer-model examinations, allowed the assignment of the absolute configurations as (+)-(8R,9S)- 5 and (?)-(8S,9R)- 5 . A detailed conformational analysis displayed excellent agreement between the results of computational methods (Monte Carlo multiple minimum simulations, analyses of the total energy as a function of the flexible dihedral angles in the molecule) and ¹H{¹H}-NOE difference spectroscopical data. It was found that (?)- 5 and (+)- 5 differ significantly in their conformational preference from their natural counterparts quinine ( 1 ) and quinidine ( 2 ). Whereas the natural alkaloids prefer the ‘open’ conformation, with the quinuclidine N-atom pointing away from the quinoline ring, analog (±)- 5 adopts preferentially (by ca. 4 kcal mol^?1) a ‘closed’ conformation, in which the quinuclidine N-atom points into the cleft of the 9,9′-spirobifluorene moiety. Since the basic quinuclidine N-atom in the ‘closed’ conformation is sterically shielded from forming strong H-bonds, the new Cinchona alkaloid analogs form less stable host-guest associations via H-bonding than quinine or quinidine.     

Geometric isomerism in the series of fluoroalkyl-containing 1,2,3-trione 2-arylhydrazones

According to the ¹H, ¹³C, and ¹⁹F NMR data, fluoroalkyl-containing 1,2,3-trione 2-arylhydrazones in CDCl₃ exist exclusively, while in (CD₃)₂CO preferentially, as isomers in which the acyl or aroyl group is involved in intramolecular hydrogen bond. The isomer structure was assigned on the basis of the chemical shifts of the carbonyl carbon atoms and fluorine atoms and carbon-fluorine spin-spin coupling constants J _C-F. X-Ray diffraction data showed that 1,2,3-trione 2-arylhydrazones in crystal have the same structure as in CDCl₃ solution. Quantum-chemical calculations were performed to rationalize predominant formation of 1,2,3-trione 2-arylhydrazone isomers with a free polyfluoroacyl group.     

Effect of H/D isotope substitution on polarizability of methanol molecules

The electron polarizabilities (α₀·10²⁴/cm³ molec.⁻¹) were estimated from the data on refractive indices and molar volumes of H/D isotopomers of methanol at 25 °C using the Lorentz-Lorentz formula: 3.265 (CH₃OH), 3.260 (CH₃OD), 3.235 (CD₃OH), and 3.231 (CD₃OD). A relationship between the isotope effects for α₀ and volume (packing) changes in the structure of liquid methanol induced by deuterosubstitution in the methanol molecule was proposed. __________ Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 8, pp. 1927–1928, August, 2005.     

Kinetic Control in the Chiral Recognition of Three‐Bladed Propellers

The ion pair of the stereolabile C₃‐symmetric, i⁺o proton complex [ 1? H]⁺ of diaza‐macropentacycle 1 and the configurationally stable Δ‐TRISPHAT ([Δ‐ 3 ]^?) anion exists in the form of two diastereomers, namely, [Δ‐( 1? H)][Δ‐ 3 ] and [Λ‐( 1? H)][Δ‐ 3 ], the ratio of which, in terms of diastereomeric excess (de) decreases in the order [D₈]THF (28 %)>CD₂Cl₂ (22 %)>CDCl₃ (20 %)>[D₈]toluene (16 %)>C₆D₆ (7 %)>[D₆]acetone (0 %) at thermodynamic equilibrium. Except in the case of [D₆]acetone, the latter is reached after a period of time that increases from 1 h ([D₈]THF) to 24 h (CDCl₃). Moreover, the initial value of the de of [ 1? H][Δ‐ 3 ] in CDCl₃, before the thermodynamic equilibrium is reached, depends on the solvent in which the sample has been previously equilibrated (sample “history”). This property has been used to show that the crystals of [ 1? H][Δ‐ 3 ] formed by slow evaporation of CH₂Cl₂/CH₃OH mixtures had 100 % de, which indicates that [ 1? H][Δ‐ 3 ] has enjoyed a crystallization‐induced asymmetric transformation. Structural studies in solution (NMR spectroscopy) and in the gas phase by calculations at the semiempirical PM6 level of theory suggest that the optically active anion is docked on the i⁺ (endo) external side of the proton complex such that one of the aromatic rings of [Δ‐ 3 ]^? is inserted into a groove of [ 1? H]⁺, a second aromatic ring being placed astride the outside i⁺ pocket. Solvent polarity controls the thermodynamics of inversion of the [ 1? H]⁺ propeller. However, both polarity and basicity control its kinetics. Therefore, the rate‐limiting steps correspond to the ion‐pair separation/recombination and [ 1? H]⁺/ 1 deprotonation/protonation processes, rather than the inversion of [ 1? H]⁺, the latter being likely to take place in the deprotonated form ( 1 ).     

Solvent effect in NMR enantiomeric analysis using (S)-1,1′-binaphthyl-2,2′-diol as a chiral solvating agent

The determination of the enantiomeric composition of chiral compounds by¹H,¹³C, and³¹P NMR spectroscopy in the presence of (S)-1,1′-binaphthyl-2,2′-diol demonstrates that the enantioselectivity of the method increases when the polarity of a solvent decreases as follows: CD₃OD-D₂O (4 ∶ 1) < CD₃OD < CDCl₃ < CDCl₃-CCl₄ (1 ∶ 1) < C₆D₆. The effect is caused by increase in stability of solvating agent-substrate complexes formed through the hydrogen bonds. Pantolactone, esters of substituted cyclopropanecarboxylic acids, amino alcohol propranolol, and 2,2′-bis(diphenylphosphinyl)-1,1′-binaphthyl were used as the substrates.     

Constants of keto-enol equilibrium of acetoacetyl- and 1,1′-bis(acetoacetyl)ferrocene in aprotic solvents at 20°

The keto-enol equilibrium of 2 × 10⁻³ M solutions of (acetoacetyl)ferrocene and 1,1′-bis(acetoacetyl)ferrocene was studied by ¹H NMR spectroscopy in a series of aprotic solvents such as DMSO-d ₆, (CD₃)₂CO, CDCl₃, CD₂Cl₂, CCl₄, and C₆D₆ at a temperature of 20°C. It was established that the calculated enolization constants increase with a decrease in the polarity of solvent molecules. The results complement and combine known empirical rules about the effect of the medium on keto-enol equilibria.     

Kinetic isotope effect in the reaction of oh radical with acetone-D6

The discharge-flow method with resonance fluorescence detection of OH radicals was applied to obtain the rate constant value of k _D = 1.95 ± 0.14 (1σ) 10¹⁰ cm³ mol^-1s^-1 at 298 K. Combination with k _H from our previous study gives the kinetic isotope effect of k _H / k _D = 5.33 ± 0.41. OH + CH₃C(O)CH₃ → Products (H) OH + CD₃C(O)CD₃ → Products(D) This revised version was published online in June 2006 with corrections to the Cover Date.     

Carbon-13 isotope effect on proton decoupled 13C and 31P n.m.r. spectra of bis(diphenylphosphino)acetylene

High resolution proton decoupled ¹³C and ³¹P n.m.r. spectra of bis(diphenylphosphino)acetylene in (CD₃)₂SO and CDCl₃ are analysed as ABX spectra to give the relative chemical shifts of the ¹³C and ³¹P nuclei as well as the spin–spin coupling constants ³J(PP) and ⁿJ(PC). The differences in ³¹P shieldings are due to secondary ¹³C isotope effects which have been observed to be negligible over more than two bonds.     

Tautomeric behaviour and isotopic multiplets in the 13C NMR spectra of partially deuterated 5‐arylazo‐pyrimidine (1H,3H,5H)‐2,4,6‐triones and 5‐arylazo‐2‐thioxo‐pyrimidine (1H,3H,5H)‐4,6‐diones—evidence for elucidation of tautomeric forms

NMR spectra of the synthesized azo dyes, 5‐arylazo‐pyrimidine (1H,3H,5H)‐2,4,6‐triones (5a–g), 1,3‐dimethyl‐5‐arylazo‐pyrimidine (1H,3H,5H)‐2,4,6‐triones (6a–g), and 5‐arylazo‐2‐thioxo‐pyrimidine (1H,3H,5H)‐4,6‐diones (7a–g) were studied in (CD₃)₂SO (three drops of CD₃OD were added into solutions of the dyes in two different concentrations). All dyes showed intramolecular hydrogen bonding. Dyes 5a–7a showed bifurcated intramolecular hydrogen bonds. Tautomeric behaviours of some of N‐methylated azo dyes (6a‐g) were studied in two different concentrations. The solvent–substrate proton exchange of dyes 5a–d, 6a and 7a–e was examined in presence of three drops of CD₃OD. The dyes which were soluble in (CD₃)₂SO containing CD₃OD showed isotopic splitting (β‐isotope effect) in the ¹³C NMR spectra. Copyright © 2009 John Wiley & Sons, Ltd.     

1H and 13C{1H} NMR spectral parameters of sulfur mustards,nitrogen mustards,and lewisites: Computing and Predicting of Reference Spectra for Chemical Identification

The ¹H and ¹³C{¹H} chemical shifts and ¹H spin–spin couplings of sulfur mustards, nitrogen mustards, and lewisites scheduled in the Chemical Weapons Convention, and those of bis(2‐chloromethyl)disulfide, were determined in CDCl₃, CD₂Cl₂, and (CD₃)₂CO. Accurate parameters of this kind of series can be used for evaluating the current molecular modeling programs and the chemical shift and coupling constant prediction possibilities of the programs. Several prediction tests were made with commercial programs, and the results are reported here. Copyright © 2012 John Wiley & Sons, Ltd.     

Complete experimental and theoretical proton and carbon nuclear magnetic resonance spectral assignments,molecular structure and conformational study of 1‐cyclohexylpiperazine and 1‐(4‐pyridyl)piperazine

The possible stable forms and molecular structures of 1‐cyclohexylpiperazine (1‐chpp) and 1‐(4‐pyridyl)piperazine (1‐4pypp) molecules have been studied experimentally and theoretically using nuclear magnetic resonance(NMR) spectroscopy. ¹³C, ¹⁵N cross‐polarization magic‐angle spinning NMR and liquid phase¹H, ¹³C, DEPT, COSY, HETCOR and INADEQUATE NMR spectra of 1‐chpp (C₁₀H₂₀N₂) and 1‐4pypp (C₉H₁₃N₂) have been reported. Solvent effects on nuclear magnetic shielding tensors have been investigated using CDCl₃, CD₃ OD, dimethylsulfoxide (DMSO)‐d₆, (CD₃)₂CO, D₂O and CD₂Cl₂. ¹H and ¹³C NMR chemical shifts have been calculated for the most stable two conformers, equatorial–equatorial (e–e) and axial–equatorial (a–e) forms of 1‐chpp and 1‐4pypp using B3LYP/6‐311++G(d,p)//6‐31G(d) level of theory. Results from experimental and theoretical data showed that the molecular geometry and the mole fractions of stable conformers of both molecules are solvent dependent. Copyright © 2009 John Wiley & Sons, Ltd.