Synthesis of newN-acylantipyrylureas and the crystal structure ofN-benzoyl-N′-[4-(2,3-dimethyl-1-phenylpyrazol-5-one)]urea

New derivatives of acylheterylureas were synthesized by reactions of acylisocyanates with 4-amino-2,3-dimethyl-l-phenylpyrazol-5-one. The structures of the compounds obtained have been established by IR and¹H NMR spectroscopy.N-Benzoyl-N′-[4-(1-phenyl-2,3-dimethylpyrazol-5-one)]urea has been studied by X-ray structural analysis. It was found that the molecule adopts ananti-syn conformation stabilized by an intermolecular hydrogen bond. In the crystal, molecules are linked in centrosymmetric dimers via intermolecular hydrogen bonds.     

Comprehensive mechanistic study of ion pair SN2 reactions of lithium isocyanate and methyl halides

The anionic S_N2 reactions NCO^? + CH₃X and ion pair S_N2 reactions LiNCO + CH₃X (X = F, Cl, Br, and I) at saturated carbon with inversion and retention mechanisms were investigated at the level of MP2/6‐311+G(d,p). There are two possible reaction pathways in the anionic S_N2 reactions, but eight in the ion pair S_N2 reactions. Calculated results suggest that the previously reported T‐shaped isomer of lithium isocyanate does not exist. All the retention pathways are not favorable based on the analysis of transition structures. Two possible competitive reaction pathways proceed via two six‐member ring inversion transition structures. It is found that there are two steps in the most favorable pathway, in which less stable lithium cyanate should be formed through the isomerization of lithium isocyanate and nucleophilic site (N) subsequently attacks methyl halides from the backside. The thermodynamically and kinetically favorable methyl isocyanate is predicted as major product both in the gas phase anionic and the ion pair S_N2 reactions. In addition, good correlations between the overall barriers relative to separated reactants, ΔH , with geometrical looseness parameter %L^≠ and the heterolytic cleavage energies of the C? X and Li? N (or Li? O) bonds are observed for the anionic and ion pair S_N2 reactions. The trend of variation of the overall barriers predicts the leaving ability of X increase in the order: F < Cl < Br < I. The polarized continuum model (PCM) has been used to evaluate the solvent effects on the two inversion pathways with six‐member transition structures for the reactions of LiNCO + CH₃X. The calculations in solution indicate that solvent effects will retard the rate of reactions and the predicted product, methyl isocyanate, is same as the one in the gas phase. © 2006 Wiley Periodicals, Inc. Int J Quantum Chem, 2006     

Vibrational relaxation induced population inversions in laser pumped polyatomic molecules

Conditions for population inversion in laser pumped polyatomic molecules are described. For systems which exhibit metastable vibrational population distributions [slow vibration—translation/rotation (V—T/R) relaxation], large, long lived inversions are possible even when the vibrational modes are strongly coupled by rapid collisional vibration—vibration (V—V) energy transfer. Overtone states of a hot mode are found to invert with respect to fundamental levels of a cold mode even at V—V steady state. Inversion persists for a V—T/R relaxation time. A gain of 4 m^?1 for the 2v₃ → v₂ transition in CH₃F (λ ≈ 15.9 μ) was found assuming a spontaneous emission lifetime of 10 s for this transition. General equations are derived which can be used to determine the magnitude of population inversion in any laser pumped, vibrationally metastable, polyatomic molecule. A discussion of factors controlling the population maxima of different vibrational states in optically pumped, V—V equilibrated metastable polyatomics is also given.     

Molecular conformations of methyl formate and methyl vinyl ether from ab initio molecular orbital calculations

Ab initio molecular orbital theory with minimal and extended basis sets and a flexible rotor geometric model has been used to investigate the rotational potential surfaces of methyl formate and methyl vinyl ether. For both molecules, the most stable structures (IA and IIA, respectively) are planar cis; additional potential minima are found which correspond to planar trans structures (IB and IIB). The latter lie respectively about 4—8 and 1—2 kcal mol^?1 above the corresponding cis rotational isomers. Methyl rotational barriers have been determined for cis and trans structures of each molecule. For trans methyl formate, there is a slight but unexpected preference for an eclipsed arrangement of the methyl group.     

Rotation and inversion in nitrosamines

Geometry optimizations of the ground states as well as of the transition states for internal rotation and inversion have been performed by the semiempirical MNDO method for dimethyl nitrosamine (1), perfluordimethyl nitrosamine (2), N-nitroso aziridine (3), and N-nitroso azetidine (4). It was found that the potential barrier to internal rotation about the N-N bond is always of lower energy than that to inversion on the nitroso nitrogen.While the ground states tend to adopt structures which enable mesomerism, the lowest transition state is characterized by a pyramidal sp³-hybridized amino nitrogen. In accordance with experimental results the low barriers to rotation of 2 (7.96 kcal mol^?1), 3 (3.38 kcal mol^?1) and 4 (9.97 kcal mol^?1) in comparison with 1 (12.54 kcal mol^?1) indicate that in donor-acceptor molecules the transfer of charge can be limited by electronic and stereochemical effects. In particular, the equivalence of the α-methylene hydrogens which was observed in the NMR-spectrum of 3 is due to unhindered rotation and ring inveirsion.     

Characterisation of selected hypnotic drugs and their metabolites using electrospray ionisation with ion trap mass spectrometry and with quadrupole time-of-flight mass spectrometry and their determination by liquid chromatography-electrospray ionisation-ion trap mass spectrometry

The electrospray ionisation-ion trap mass spectrometry (ESI-MSⁿ) of selected hypnotic drugs, i.e. zopiclone, zolpidem, flunitrazepam and their metabolites have been investigated. Sequential product ion fragmentation experiments (MSⁿ) have been performed in order to elucidate the degradation pathways for the [M+H]⁺ ions and their predominant fragment ions. These MSⁿ experiments show certain characteristic fragmentations in that functional groups are generally cleaved from the ring systems as neutral molecules such as H₂O, CO, CO₂, NO₂, amines and HF. When an aromatic entity is present in a drug molecule together with a nitrogen-containing saturated ring structure as with zopiclone and its N-desmethyl metabolite fragmentation initially occurs at the latter ring with the former being resistant to fragmentation. The structures of fragment ions proposed for ESI-MSⁿ can be supported by electrospray ionisation-quadrupole time-of-flight mass spectrometry (ESI-QTOF-MS).These molecules can be identified and determined in mixtures at low ng/ml concentrations by the application of liquid chromatography (LC)-ESI-MSⁿ which can be used for their analysis in saliva samples.This paper includes a tabulation of mass losses/signals at low m/z values for these hypnotic drugs and many others in recent publications which will be of value in the characterisation of drug metabolites of unknown structure and also natural product pharmaceuticals isolated from plants, etc.     

Spectroscopic Properties,Conformation and Structure of Difluorothiophosphoryl Isocyanate in the Gaseous and Solid Phase

Difluorothiophosphoryl isocyanate, F₂P(S)NCO was characterized with UV/vis, NMR, IR (gas and Ar-matrix), and Raman (liquid) spectroscopy. Its molecular structure was also established by means of gas electron diffraction (GED) and single crystal X-ray diffraction (XRD) in the gas phase and solid state, respectively. The analysis of the spectroscopic data and molecular structures is complemented by extensive quantum-chemical calculations. Theoretically, the C_s symmetric syn-conformer is predicted to be the most stable conformation. Rotation about the P−N bond requires about 9 kJ mol⁻¹ and the predicted existence of an anti-conformer is dependent on the quantum-chemical method used. This syn-orientation of the isocyanate group is the only one found in the gas phase and contained likewise in the crystal. The overall molecular structure is very similar in gas and solid, despite in the solid state the molecules arrange through intramolecular O⋅⋅⋅F contacts into layers, which are further interconnected by S⋅⋅⋅N, S⋅⋅⋅C and C⋅⋅⋅F contacts. Additionally, the photodecomposition of F₂P(S)NCO to form CO, F₂P(S)N, and F₂PNCO is observed in the solid Ar-matrix.     

Granisetron,an antiemetic drug,and its cobalt complex

The crystal structures of granisetron [systematic name: 1‐methyl‐N‐(9‐methyl‐9‐azabicyclo[3.3.1]nonan‐7‐yl)indazole‐3‐carboxamide], C₁₈H₂₄N₄O, (I), an antinauseant and antiemetic agent, and its Co^II complex, diaqua[1‐methyl‐N‐(9‐methyl‐9‐azoniabicyclo[3.3.1]nonan‐7‐yl)indazole‐3‐carboxamide]cobalt(II) tetrachloride dodecahydrate, [Co(C₁₈H₂₅N₄O)₂(H₂O)₂]Cl₄·12H₂O, (II), have been determined by X‐ray diffraction. The granisetron molecule is in an extended conformation in both structures. Twisting of the central carboxamide group facilitates the Co^II coordination in (II). The Co^II atom is located on an inversion centre. The azabicyclononane ring adopts a chair–boat conformation in both structures. The molecules in (I) are linked into centrosymmetric dimers and form tetracyclic rings through C—H...O hydrogen‐bonding interactions. The simultaneous presence of free chloride ions in conjunction with a number of hydration water molecules in (II) provides interesting hydrogen‐bond patterns. This study can aid in the investigation of the properties of metal complexes with active pharmaceuticals in which the drug molecules play the role of a ligand.     

The solid-state structures of the ethanol solvated complexes of para-sulphonato-calix[4]arene with magnesium and calcium ions

The structures ethanol solvated complexes of para-sulphonato-calix[4]arene with magnesium and calcium have been determined. Both show the classical bilayer structure of para-sulphonato-calix[4]arene. The cations are situated between the bilayers. In the case of the magnesium complex the cation is octahedrally coordinated by six water molecules, however for the calcium complex the cation is coordinated in two different geometries by water molecules, bridging oxygen atoms of the sulphonate anions and an oxygen of an ethanol molecule. Both complexes contain an ethanol molecule embedded in the macrocyclic cavity.     

The role of internal H-bonding in the conformational preferences of some molecules of the formula CH3CHYCH2X

The conformational energies of 1-amino-2-propanol, 2-amino-1-propanol and 1,2-diaminopropane are studied using ab initio molecular orbital theory employing minimal (STO-3G) and extended (4-31G) basis sets. Calculations at both levels of theory generally favor conformations stabilized by internal H-bonding for all molecules considered. Results are first presented for conformations employing assumed geometries. Since the conformational energy differences as found by the initial set of calculations are in some cases rather small it then becomes necessary to introduce geometry optimizations into the study at the minimal STO-3G level. In addition, to get a better estimate of the energy differences of the various conformations 4-31G calculations are performed on the STO-3G optimized structures. These latter results indicate the following, (a) For 1-amino-2-propanol only one conformation that is stabilized by intramolecular H-bonding is low in energy; this has the methyl and amino groups anti. The other H-bonded conformer, where the methyl and amino groups are gauche, is predicted to be ca. 1.2 kcal mol^?1 less stable. Similar findings for this molecule have recently been provided by micro-wave spectroscopy. (b) For 2-amino-1-propanol the two H-bonded conformers are only separated by about 0.5 kcal mol^?1, with the anti conformer being more stable. Micro-wave spectroscopy again supports these calculations. (c) For 1,2-diaminopropane the gauche conformer is predicted to be of rather high energy (ca. 2.5 kcal mol^?1) compared to the corresponding anti H-bonded conformer. The value of 2.5 kcal mol^?1should be taken as an upper limit, since the geometry optimization of the gauche conformer of 1,2-diaminopropane is incomplete compared to the optimization carried out for the anti conformer.     

Synthesis, NMR, X-ray structural analyses and complexation studies of new Ag selective calix[4]arene based dipodal hosts—a co-complexation of neutral and charged species

New podands based on the p-tert-butylcalix[4]arene unit with substitution at the lower rim incorporating imine units, have been synthesized in high yield by simple condensation method. These podands have been shown to extract and transport Ag⁺ selectively over alkali, alkaline earth metal cations, Zn²⁺, Pb²⁺ and Hg²⁺ ions, from neutral aqueous phase to organic phase. In all the ligands the calix unit has been found to be present in a cone conformation except for the one having pyridine as end group, at the ortho position. It has been isolated in two conformations; cone and 1,2-alternate. To the best of our knowledge, this may be the first 1,3-lower rim substituted calix[4]arene to exist in a 1,2-alternate conformation and is among a few known compounds with this conformation in the general class of calix[4]arenes. A complex of this ligand, which happens to be the highest extractant of Ag⁺ has been isolated and characterized using mass, ¹H and ¹³C NMR spectroscopy's and elemental analysis. The spectroscopic evidence and molecular modelling studies performed on the complex suggest a participation of the imine and pyridine nitrogens and two of the ether oxygens in coordination to the metal ion. The X-ray crystal structures of three of the ligands establish the formation of inclusion complexes with polar acetonitrile solvent molecules. The ¹H and ¹³C NMR spectra of all the compounds, taken in CDCl₃, show the presence of acetonitrile molecules in the cavity of the calix[4]arene, indicating inclusion of the neutral guest molecules in the solution phase as well. For one of the podands X-ray crystal structure has shown a formation of clatharate complex of chloroform with the ligand which has rarely been found in the case of calix[4]arenes.     

Effects of microhydration on the characteristics of cation–phenol complexes

The properties of complexes formed by phenol and K⁺, Na⁺, Li⁺ and Mg²⁺ in the presence of up to four water molecules have been studied by means of computational methods. The interaction becomes stronger as the size of the cation decreases, showing almost no preference between coordinating to the aromatic ring or to the hydroxyl oxygen. As water molecules are introduced, a variety of stable structures arise, where water molecules establish hydrogen bonds among themselves and with the hydroxyl group of phenol. For the most polarizing cations, the strong cation···water interaction gives most stable minima corresponding to arrangements with water molecules and phenol coordinated directly to the cation, with no significant hydrogen bonds among them. However, in Na⁺ complexes and especially in K⁺ ones, the interaction with the cation is weaker, so hydrogen bond formation starts to be competitive as more water molecules are included, the most stable minima corresponding to structures where not all water molecules or phenol are directly bound to the cation. This behavior is also reflected on the predicted vibrational spectra, which agree with those determined experimentally. Up to three water molecules, only for K⁺ and to a less extent Na⁺, stable minima are found showing red-shifted O–H stretching bands corresponding to water···water and water···phenol hydrogen bonds. With four water molecules, at least one water molecule is located in a second solvation shell, all cations exhibiting red-shifted bands.     

Electron diffraction study of the trichloromethyltrichlorogermane molecular structure and estimation for torsional barrier

The molecular geometry (in terms of r_a and r_g internuclear distances) and mean amplitudes of vibration of CCl₃GeCl₃ have been determined by electron diffraction. The bond lengths are similar to those found in analogous molecules. Although bond angles of unambiguous physical definition have not been determined it is established that the carbon and germanium bond configurations deviate little from the regular tetrahedral arrangement. The molecule performs large amplitude motion around the carbon-germanium bond. The torsional barrier was estimated to be 1.1 kcal mole^?1 using J. Karle's method [8].     

Synthesis and crystal structure analysis of 2-(4-fluorobenzyl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazole and its chlorophenyl derivative

Preparations of 2-(4-fluorobenzyl)-6-phenylimidazo[2,1-b][1,3,4]thiadiazole (3a) and its chlorophenyl derivative (3b) are described. Preliminary analysis was done spectroscopically by means of ¹H NMR, ¹³C NMR spectra, mass spectra and elemental analyses. Further the structures were confirmed by X-ray crystal structure analyses. The compound (3a) has crystallized in a triclinic P-1 space group with three independent molecules in the asymmetric unit, while the compound (3b) belongs to P2₁/c space group with one molecule in the asymmetric unit. The molecule (3b) differs from molecule (3a) by the presence of chlorine substituent. Additionally, the imidazo-thiadiazole entity is as usual planar. Intramolecular C–H⋯N hydrogen bonding between the imidazole and the phenyl ring of the molecule can be observed in (3a) & (3b). The molecules of (3a) are linked into two dimensional supramolecular hexagonal hydrogen bonded network sustained by C–H⋯F interaction, while those of (3b) are linked by bifurcated C–H⋯N interactions. Further, the molecular packing of both the compounds is stabilized by π–π stacking interactions between the benzene and imidazo-thiadiazole ring systems.     

π-Bond Configurations,Conformations, and Dynamic Behaviour of Benzo[c]octalene and Dibenzo[c,j]octalene

The π-bond configurations, the conformations, and the dynamic behaviour of dibenzo [c,j]octalene (2) and of benzo [c]octalene (3) have been investigated by ¹³C-NMR. spectroscopy at different temperatures. Dibenzooctalene was found to present π-bond fixation in the octalene unit as in 2b ; with this π-bond fixation the molecule is not planar and takes two different conformations which are rapidly interconverted by inversion of one cyclooctatetraene ring. Monobenzooctalene (3) also presents π-bond fixation in the octalene unit but exists as two valence isomers, 3b and 3c. Isomer 3c dominates the dynamic equilibrium. With this π-bond configuration, the molecule is chiral but undergoes several isodynamic processes, namely inversion of the cyclooctatriene and/or of the cyclooctatetraene ring. The valence isomer 3b can have two different conformations which are rapidly interconverted by inversion of one cyclooctatetraene ring. The interconversion 3c ? 3b implies the occurrence of a π-bond shift process; this process affects the ¹³C-NMR. lineshape above 50°.     

A quantum chemical study of tricyclo[3.2.0.0]heptane: a new hypothetical molecule with unusual spatial structure. Similarities and differences with syn- and anti-tricyclo[3.2.0.0]heptanes

HF and MP2 calculations with the 6-31G^∗∗ and 6-311G^∗∗ basis sets for the titled molecules and those at MP2/cc-pVTZ level for the hypothetical tricyclo[3.2.0.0^1,3]heptane indicate that the latter molecule should have a carbon atom with highly unusual configuration strongly departing from the tetrahedral one. Both analysis of vibrational frequencies of this molecules and comparison of its energy with those of known isomeric syn- and anti- tricyclo[3.2.0.0^2,4]heptanes as well as the DFT analysis of its plausible decomposition routes performed at the DFT level indicate that it could be a plausible synthetic target.     

Spectroscopy of benzene complexes with perylene and other aromatic species

The fluorescence excitation spectra are reported of complexes of benzene with perylene and anthracene. Some correlations are established between the results of simple potential energy calculations and the experimental data, in regard to the structures and binding energies of a number of different complexes. In particular, while the anthracenebenzene complex is somewhat similar to one postulated form of the benzene dimer where parallel, but displaced rings are found, benzene appears to occupy a center-of-mass position on perylene. The spectrum of perylenebenzene also shows evidence of strong coupling between internal modes of the two molecules near 1600 cm⁻¹. The other major perturbation of the spectrum involves damping of the out-of-plane “butterfly” motion of perylene by the adsorbed benzene molecule. The principal low-frequency mode, known to be a v = 0 → v = 2 transition in the bare molecule, at 95 cm⁻¹, is replaced in the benzene 1:1 and 2:1 complexes by a transition, at 68 cm⁻¹. Furthermore, unlike the bare molecule, the ground state frequency of the perturbed out-of-plane mode is very similar to that of the excited state. Indications from these data support the idea that the equilibrium out-of-plane distortion of perylene in a complex with benzene is rather different from that observed in the bare perylene molecule.     

Investigations on mixed water-clusters: Gas phase titration with cyclopentanone and identification of some isomers by time-of-flight mass spectrometry

Mixed-clusters of water with cyclopentanone have been investigated using high resolution time-of-flight mass spectrometry. These clusters are synthesized in a gas-aggregation source at comparatively higher temperature. They contain water-cluster at the core and cyclopentanone molecules hydrogen bonded through ketone oxygen with the dangling OH available at the core. Thus these mixed-clusters may also be considered as the products of a titration in gas phase. The growth reaction reveals that all clusters are protonated. From the configuration of dimer and tetramer, it is suggested that the proton resides as an Eigen ion in the core. The protonated mixed-clusters containing six, seven and eight water molecules substantiate the hydronium contained hexa, hepta and octamer water-cluster structures predicted by [KJ(H₃O)⁺] model calculations. For clusters with 9–19 water molecules, the core appears to have configurations that give less than the predicted number of dangling bonds. In large size clusters having more than 20 water molecules, the water-core appears to have open configuration like the melted structures obtained as a result of increase in temperature.     

Atomic inversion barriers of sulphur and selenium in the dimethylsulphide and dimethylselenide complexes of the halogeno carbonyls of rhenium

We have synthesised four rhenium carbonyl complexes of general formula [ReX(CO)₃(Me₂E)₂] (X  Cl, Br, I, E  S, Se), and studied their temperature variable NMR spectra. All complexes were formed as the fac isomer, with the exception of [ReI(CO)₃(Me₂Se)₂], which was obtained as a mixture of mer and fac forms. In all of these fac complexes pyramidal inversion of sulphur or selenium atoms has been demonstrated, and energy barriers to inversion have been determined either by computer simulation of complete line shapes or by coalescence temperature methods. The value of ΔG^≠ for inversion in this class of complex has been found to be about 17 kJ mol^?1 higher for selenium than for sulphur, and variation of the cis halogen made no pronounced effect.     

Synthesis and crystal structure of diaqua(trinitrato)iron(III) 18-crown-6

A novel complex adduct, diaqua(trinitrato)iron(III) 18-crown-6, [Fe(NO₃)₃(H₂O)₂] · 18-crown-6, was synthesized and its crystal structure was studied by X-ray diffraction: space group C2/c, a = 10.073, b = 18.069, c = 25.326 Å, β = 91.51°, Z = 8. The structure was solved by the direct method and refined by the full-matrix least-squares method in the anisotropic approximation to R = 0.076 for 4090 independent reflections (CAD-4 automated diffractometer, λMoK_α). The structure contains isolated complex molecule [Fe(NO₃)₃(H₂O)₂] and two halves of independent molecules 18-crown-6, one of which is statistically disordered about axis 2, while another one is located around the inversion center and is somewhat disordered with respect to the latter. In the complex molecule, the coordination polyhedron of the Fe³⁺ cation is a distorted pentagonal bipyramid with five O atoms of three NO ₃ ^? ligands in a base and two O atoms of two water molecules in the axial vertices. The alternating complex molecules and the disordered 18-crown-6 molecules are joined by hydrogen bonds into “thick” infinite chains along the z axis.