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The X-ray crystal structure of 2-benzyl-1H-benzimidazole, 2BnBzIm, was determined at 293 K showing no dynamic phenomena (disorder) of any class. On the other hand, some C NMR signals were absent in the CPMAS spectrum (100 MHz, 300 K). We decided to carry out variable-temperature SSNMR and discovered that the missing signals are ortho and meta carbons of the phenyl ring of the benzyl group. Line-shape analysis and the Eyring equation were used to determine the barrier, which was compared with the calculated DFT for the gas phase that it is much lower., This work was supported by Ministerio de Economía, Industria y Competitividad of Spain (CTQ2014‐56833‐R and CTQ2015‐63997‐C2‐2‐P) and Comunidad Autónoma de Madrid (Project FOTOCARBON, ref. S2013/ MIT2841). Carla I. Nieto is indebted to UNED for a predoctoral contract “FPI Grupos de Investigación.”

A series of fourteen new asymmetrical 1,3-diketone derivatives have been synthesized and evaluated in the ABTS, FRAP and DPPH assays as a new chemotype with antioxidant and drug-like properties. All the compounds displayed low cytotoxicity in comparison to curcumin against the human neuroblastoma SH-SY5Y cell line. Among them, (3Z,5E)-6-(2,5-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (6b) and (3Z,5E)-6-(2,3-difluoro-4-hydroxy-phenyl)-1,1,1-trifluoro-4-hydroxyhexa-3,5-dien-2-one (7b) with excellent solubility and chemical stability in biorelevant media, have also shown a similar Fe+2 chelation behavior to that of curcumin. Additionally, both derivatives 6b and 7b have afforded good neuroprotection activity against H2O2 induced oxidative stress in the same neuronal cell line, with a significant reduction of intracellular ROS levels, in parallel with a good recovery of the Mitochondrial Membrane Potential (&Delta, &Psi, m). Compounds 6b and 7b with a promising antioxidant and drug-like profile, with low cytotoxic and good neuroprotectant activity, constitute a new interesting chemical class with high potential as new therapeutic agents against neurodegenerative diseases.

This paper reports the 1H, 13C and 15N NMR experimental study of five benzimidazoles in solution and in the solid state (13C and 15N CPMAS NMR) as well as the theoretically calculated (GIAO/DFT) chemical shifts. We have assigned unambiguously the "tautomeric positions" (C3a/C7a, C4/C7 and C5/C6) of NH-benzimidazoles that, in some solvents and in the solid state, appear different (blocked tautomerism). In the case of 1H-benzimidazole itself we have measured the prototropic rate in HMPA-d18.

This work was financed by the Spanish Ministerio de Ciencia e Innovacion (MICINN) (CTQ2010-16122) and the Ministerio de Economia y Competitividad (MEC) (CTQ2012-35513-C02-02) and by the Comunidad Autonoma de Madrid (project MADRISOLAR2, ref. number S2009/PPQ-1533). The authors thank Dr. Ibon Alkorta for his help with the CSD and Dr. Ma Angeles Garcia for her assistance in recording the variable-temperature NMR spectra.

2-Propyl-1H-benzimidazole (2PrBzIm) is a small molecule, commercially available, which displays a curious behavior in the solid state. 2PrBzIm, although devoid of chirality by fast rotation about a single bond of the propyl group in solution, crystallizes as a conglomerate showing chiroptical properties. An exhaustive analysis of its crystal structure and a wide range of experiments monitored by vibrational circular dichroism spectroscopy eliminated all possibilities of an artifact. What remains is a new example of the unexplained phenomenon of persistent supramolecular chirality., The authors thank F. Hermoso-Torres, M. Gómez-Torres, C. Benıt́ ez-Guerrero, Dr. M. Loṕ ez-Sań chez, and Dr. J. L. Zafra- Paredes for technical assistance. The authors also thank the Univ. de Jaén for financial support, for bridge projects (UJA2015/08/07 and UJA2016/08/15) and access to its CICT instrumental facilities, and they also thank the Univ. de Málaga for its SCAI instrumental facilities. This work was supported by Ministerio de Economıá y Competitividad of Spain (CTQ2015-63997-C2-2-P and CTQ2014-56833-R), CICE/Junta de Andalucıá (P08-FQM-04096), CICE/JAFEDER- UJA: Plan de Fortalecimiento de las Capacidades de I+D+i/2014-15 (UJA2013/08/03), Comunidad Autónoma de Madrid (Project Fotocarbon, Ref. No. S2013/MIT-2841), by the Basque Government (IT779-13), and the Spanish MEC (FIS2010-19609-C02-01). M.M.Q.M. thanks the Univ. de Jaén for a predoctoral fellowship, and J.R.A.M. thanks Junta de Andalucıá for a postdoctoral grant

The structure of three fluorinated NH-indazolinones, two oxo derivatives and one 3-hydroxyindazole, has been determined by 13C and 15N solid state NMR. For two of them, X-ray crystallography confirmed the results on the tautomeric forms, 4,5,6,7-tetrafluoroindazolin-3-one crystallizing in P2 1/c monoclinic space group and 6,7-difluoroindazolin-3-one in P2 1/n monoclinic space group, proving once more the efficiency of the combined use of both techniques in structural determination. DFT theoretical calculations, gas phase, water-PCM and one explicit water molecule, support the results. © 2012 Elsevier B.V. All rights reserved.

3-Bromo-1-methyl-7-nitro-1H-indazole (1), 3-bromo-2-methyl-7-nitro-2H- indazole (2) and 3,7-dinitro-1(2)H-indazole (3) have been synthesized and characterized by X-ray diffraction, 13C and 15N NMR spectroscopy in solution and in solid-state. The dihedral angles obtained in the crystal structures are in good agreement with the molecular parameters calculated using DFT B3LYP calculations employing the 6-311++G(d,p) basis set. Compounds 1 and 2 present intermolecular halogen bonds between the bromine and the oxygen atoms of the nitro group and in compound 3 inter- and intramolecular hydrogen bonding exists. © 2010 Published by Elsevier B.V.

Eleven new heterocyclic mono-and diquaternary salts have been prepared by reaction of 1,2-bisazolyl- and 1,2-bisbenzazolyl-ethanes with methyl sulfate or methyl fluorosulfonate. Their structure has been established by means of 1H and 13C NMR spectroscopy. Homonuclear COSY and NOESY experiments and 2D-heteronuclear correlations have been performed when necessary to assign all NMR signals.

Nine new pyrazolinones are described together with the crystal structure of one of them, namely 3-(4-chloropyrazol-1-yl)-4,4-dichloro-2-pyrazolin-5-one, 8, which has been solved, by X-ray crystallography. The molecule is planar since it lies on a mirror plane and packs first in chains through hydrogen bonds, then in sheets through strong Cl…O interactions. An NMR study in the solid state and in solution proves that the major tautomer is the 3-pyrazolin-5-one c..

A thermochemical and thermophysical study has been carried out for crystalline barbital [5,5′-diethylbarbituric acid]. The thermochemical study was made by static bomb combustion calorimetry, from which the standard (p{ring operator} = 0.1 MPa) molar enthalpy of formation of the crystalline barbital, at T = 298.15 K, was derived as -(753.0 ± 1.8) kJ · mol-1. The thermophysical study was made by differential scanning calorimetry over the temperature interval (265 to 470) K. A solid-solid phase transition was found at T = 413.3 K. The vapour pressures of the crystalline barbital were measured at several temperatures between T = (355 and 377) K, by the Knudsen mass-loss effusion technique, from which the standard molar enthalpy of sublimation, at T = 298.15 K was derived as (117.3 ± 0.6) kJ · mol-1. The combination of the experimental results yielded the standard molar enthalpy of formation of barbital in the gaseous phase, at T = 298.15 K, as -(635.8 ± 1.9) kJ · mol-1. This value is compared and discussed with our theoretical calculations by several methods (Gaussian-n theories G2 and G3, complete basis set CBS-QB3, density functional B3P86 and B3LYP) by means of atomization and isodesmic reaction schemes. © 2009 Elsevier Ltd. All rights reserved.

The structures of four NH-pyrazoles, (E)-3,5-bis[β-(4-hydroxy-3- methoxyphenyl)-ethenyl]-1H-pyrazole (3), (E)-3(5)-[β-(4-hydroxy-3- methoxyphenyl)-ethenyl]-5(3)-methyl-1H-pyrazole (4), (E)-3(5)-[β-(4- hydroxy-3-methoxyphenyl)-ethenyl]-4,5(3)-dimethyl-1H-pyrazole (5) and (E)-3(5)-[β-(3,4-dimethoxyphenyl)-ethenyl]-4-methyl-5(3) -phenyl-1H-pyrazole (8), have been determined by X-ray crystallography. Compounds that have a phenol residue crystallize forming sheets that are stabilized by a complex pattern of hydrogen bonds between a unique tautomer (4), or by a 2: 1 mixture of both tautomers (5) (these tautomers being identical in the case of 3). Pyrazole 8, which lacks OH groups, crystallizes in cyclic dimers that are stabilized by N-H⋯N hydrogen bonds. The tautomerism in solution and in the solid state was determined by 13C and 15N CPMAS NMR spectroscopy. For compounds 4, 5 and 8, the solid state results agree with those observed by crystallography; the most abundant tautomer in solution coincides with the tautomer present in the solid state (4 and 8) or with the most abundant tautomer in the crystal (5). © The Royal Society of Chemistry and the Centre National de la Recherche Scientifique.

Thermophysical and thermochemical studies have been carried out for crystalline parabanic acid. The thermophysical study was made by differential scanning calorimetry, DSC, over the temperature interval between T = (263 and 473) K. Two phase transitions were found: at T = (392.3 ± 1.6) K with the enthalpy of transition of (2.1 ± 0.4) kJ · mol−1 and at T = (509.8 ± 1.5) K, when the compound was scanned to its fusion temperature. The standard (p∘ = 0.1 MPa) molar enthalpy of formation, at T = 298.15 K, for crystalline parabanic acid was determined using static-bomb combustion calorimetry as −(590.2 ± 1.0) kJ · mol−1. The standard molar enthalpy of sublimation, at T = 298.15 K, was derived from the variation of their vapour pressures, measured by the Knudsen-effusion method, with the temperature. These two thermochemical parameters yielded the standard molar enthalpy of formation in the gaseous phase, at T = 298.15 K, as −(470.8 ± 1.2) kJ · mol−1., Thanks are due to Gabinete de Relações Internacionais da Ciência e do Ensino Superior (GRICES), Lisbon, Portugal, and Consejo Superior de Investigaciones Cientı´ficas (CSIC), Madrid, Spain for a joint research project GRICES/CSIC. Thanks are due to Fundação para a Ciência e a Tecnologia, F.C.T., Lisbon, Portugal, and to FEDER for financial support to Centro de Investigação em Quı´mica da Universidade do Porto (CIQ-U.P.). V.L.S.F. thanks Faculdade de Ciências for a research grant. The Spanish co-authors gratefully acknowledged the support of DGES/MEC (CTQ 2006-02586, CTQ 2006-12745/BQU, CTQ 2006-10178/BQU, CTQ 2007-60895/BQU) and to Prof. Ibon Alkorta for his help.

Structural data are reported on sixteen ketoenols of β-diketones: solution NMR, solid-state NMR (CPMAS and MAS) and X-ray crystallography (four compounds, where three are new). The emphasis is on the tautomerism between both ketoenols, in solution and in the solid state. GIAO/B3LYP/6-311++G(d,p) and Quantum ESPRESSO (QE) calculations were used and compared. For average values, the GIAO/DMSO-PCM is enough, but splittings can only be approached by using QE. A case of rotational disorder has been analyzed. Some anomalies related to C-F bonds and to the C-CF group have been detected., This work has been financed by Ministerio de Economía y Competitividad of Spain (CTQ2012-35513-C02-02 and CTQ2014-56833-R) and Comunidad Autónoma de Madrid (Project Fotocarbon, S2013/MIT-2841). One of us (C. I. Nieto) is indebted to Struct Chem (2016) 27:705–730 729 123 UNED for a predoctoral fellowship (FPI ‘‘Grupos de Investigación’’ UNED). Financial support from the Universidad de Buenos Aires and the CONICET is also greatly acknowledged.

The enthalpies of combustion, heat capacities, enthalpies of sublimation and enthalpies of formation of 2-tert-butylbenzimidazole (2tBuBIM) and 2-phenylimidazole (2PhIM) are reported and the results compared with those of benzene derivatives and a series of azoles (imidazoles, pyrazoles, benzimidazoles and indazoles). Theoretical estimates of the enthalpies of formation were obtained through the use of atom equivalent schemes. The necessary energies were obtained in single-point calculations at the B3LYP/6-311++G(d,p) on B3LYP/6-31G* optimized geometries. The comparison of experimental and calculated values of all studied compounds bearing H (unsubstituted), methyl (Me) ethyl (Et), propyl (Pr), isopropyl (iPr), tert-butyl (tBu), benzyl (Bn) and phenyl (Ph) groups show remarkable homogeneity. The remarkable consistency of both the calculated and experimental results allows us to predict with reasonable certainty the missing experimental values. The crystal and molecular structure of the 2-benzylbenzimidazole (2BnBIM) has been determined by X-ray analysis. The observed molecular conformation permits the crystal being built up through N−H···N hydrogen bonds and van der Waals contacts between the molecules. An attempt has been made to relate the crystal structure to the enthalpies of sublimation., Thanks are due to Instituto de Cooperac¸a˜o Cientı´fica e Tecnolo´gica International (ICCTI), Lisbon, Portugal, and Consejo Superior de Investigaciones Cientı´ficas (CSIC), Madrid, Spain. L.M.P.F.A. thanks Fundac¸a˜o para a Cieˆncia e Tecnologia (FCT), Lisbon, Portugal, for the award of a postdoctoral fellowship (PRAXIS XXI/BPD/16319/98). This work has also been financed by DGICYT (BQU-2003- 00894, -00976 and -01251).

The standard (p° = 0.1 MPa) molar enthalpy of formation for gaseous 2-phenylbenzimidazole (2-PhBIM) and 2-benzylbenzimidazole (2-BzBIM) were derived from the standard molar enthalpies of combustion, at T = 298.15 K, measured by static bomb calorimetry, and the standard molar enthalpy of sublimation, at T = 298.15 K, measured by Calvet microcalorimetry in the case of 2-phenylbenzimidazole or derived from the variation of the vapour pressures, determined by the Knudsen effusion technique, with temperatures between (393 and 412) K for 2-benzylbenzimidazole. Heat capacities, in the temperature ranges from (268.15 to 322.10) K for 2-phenylbenzimidazole and (270.15 to 316.02) K for 2-benzylbenzimidazole, were also measured with a differential scanning calorimeter. ΔcHm°(cr)/kJ·mol-1ΔcrgHm°(T=298.15K)/ kJ·mol-12-Phenylbenzimidazole (2-PhBIM)-6679.8 ± 0.9123.0 ± 1.72-Benzylbenzimidazole (2-BzBIM)-7327.1 ± 4.0136.2 ± 0.5 © 2005 Elsevier Ltd. All rights reserved.

The enthalpies of combustion, heat capacities, enthalpies of sublimation and enthalpies of formation of 2-methylbenzimidazole (2MeBIM) and 2-ethylbenzimidazole (2EtBIM) are reported and the results compared with those of benzimidazole itself (BIM). Theoretical estimates of the enthalpies of formation were obtained through the use of atom equivalent schemes. The necessary energies were obtained in single-point calculations at the B3LYP/6-311+G(d,p) on B3LYP/6-31G* optimized geometries. The comparison of experimental and calculated values of benzenes, imidazoles and benzimidazoles bearing H (unsubstituted), methyl and ethyl groups shows remarkable homogeneity. The energetic group contribution transferability is not followed, but either using it or adding an empirical interaction term, it is possible to generate an enormous collection of reasonably accurate data for different substituted heterocycles (pyrazole-derivatives, pyridine-derivatives, etc.) from the large amount of values available for substituted benzenes and those of the parent (pyrazole, pyridine) heterocycles., We acknowledge the financial support of the DGI/MCyT (project nos. BQU-2003-00976, 01251 and 05827). This work has been partially supported by the DGI project no. BQU-2003-00894. A generous allocation of computational time at the CCC of the Universidad Auto´noma de Madrid is also gratefully acknowledged. Thanks are also due to Instituto de Cooperac¸a˜o Cientı´fica e Tecnolo´gica Internacional (ICCTI), Lisbon, Portugal, and Consejo Superior de Investigaciones Cientı´ficas (CSIC), Madrid, Spain, for a joint research project ICCTI/CSIC. MLPFA thanks Fundac¸a˜o para a Cieˆncia e Tecnologia (FCT), Lisbon, Portugal, for the award of a postdoctoral fellowship (PRAXIS XXI/BPD/16319/98) and MT thanks MECD/SEEU (AP 2002-0603), Spain, for financial support.

Six new 3(5)-trifluoromethyl-5(3)-substituted-styryl-1H-pyrazoles have been synthesized and their tautomerism studied in solution and in the solid state. The determination of their structures has been based on multinuclear NMR spectroscopy together with GIAO/B3LYP/6-311++G(d,p) theoretical calculations of eight structures for each pyrazole (two tautomers and four conformations). Five out of the six compounds present inhibition percentages of the iNOS isoform higher than 50%. With regard to the nNOS inhibitory activity, only two of the studied compounds show an inhibition of about 50%. Finally, concerning the eNOS, there is a compound presenting a low percentage of inhibition (40.2%) attaining in the other cases 50%., This work has been financed by Ministerio de Economía y Competitividad of Spain (CTQ2014-56833-R, RD12/0043/0005, and PI13-00981) and Comunidad Autonoma de Madrid (Project MADRISOLAR2, ref. S2009/PPQ-1533). One of us (C. I. Nieto) is indebted to UNED for a predoctoral fellowship (FPI “Grupos de Investigacion” UNED).

A series of new (E)-3(5)-[β-(aryl)-ethenyl]-5(3)-phenyl-1H-pyrazoles bearing fluorine atoms at different positions of the aryl group have been synthesized starting from the corresponding β-diketones. All compounds have been characterized by elemental analysis, DSC as well as NMR (H, C, F and N) spectroscopy in solution and in solid state. Three structures have been solved by X-ray diffraction analysis, confirming the tautomeric forms detected by solid state NMR. The in vitro study of their inhibitory potency and selectivity on the activity of nNOS and eNOS (calcium-calmodulin dependent) as well as iNOS (calcium-calmodulin independent) isoenzymes is presented. A qualitative structure-activity analysis allowed the establishment of a correlation between the presence/absence of different substituents with the inhibition data proving that fluorine groups enhance the biological activity. (E)-3(5)-[β-(3-Fluoro-4-hydroxyphenyl)-ethenyl]-5(3)-phenyl-1Hpyrazole (13), is the best inhibitor of iNOS, being also more selective towards the other two isoforms., This work has been financed by Ministerio de Ciencia e Innovación (CTQ2010-16122) and Ministerio de Economía y Competitividad of Spain (CTQ2014-56833-R, RD12/0043/0005, and PI13-00981) and Comunidad Autónoma de Madrid (Project MADRISOLAR2, ref. S2009/PPQ-1533). One of us (C. I. Nieto) is indebted to UNED for a predoctoral fellowship (FPI “Grupos de Investigación” UNED). We acknowledge support by the CSIC Open Access Publication Initiative through its Unit of Information Resources for Research (URICI).

The secondary structure of the title compound, C 8 H 7 N 3 O, consists of O-H…N hydrogen-bonding catemers, similar to those of the parent 1,2,4-triazole, where the molecules are linked by N-H…N bonds. Chains related by translation are linked by C-H(triazole)…O/N interactions to give a tertiary structure of corrugated sheets parallel to the ac plane. The quaternary structure is due to C-H(Ph)…O contacts and to the stacking of triazole rings from centrosymmetrically related sheets.

The crystal and molecular structure of [14]paracyclo-bis-(1,2)pyrazoliumphane dibromide (1a) has been determined. The compound exists in the solid state in the chair (C) conformation while both chair (C) and boat (B) conformations are present in solution in comparable amounts. The barrier to the C ⇌ B interconversion has been determined by 1H NMR spectroscopy ( ΔG ‡ ≈ 17 kcal mol −1 ). AM1 semiempirical calculations conveniently reproduce the difference in stability between the chair (C) and the boat (B) conformations. [14]Paracyclo-bis-(1,2)pyrazolium-phane dibromide exists in the solid state in the chair conformation (X-ray crystallography) while both chair and boat conformations are present in solution in comparable amounts. The barrier to the chair boat interconversion has been determined by 1H NMR spectroscopy ( ΔG‡ ≈ 17 kcal mol −1 ).

The molecular and crystal structure of 2-(2′-hydroxyphenyl)imidazole (2) and 1-methyl-2-(2′-hydroxyphenyl)imidazole (5) have been determined by X-ray analysis. Compound (2) presents a strong intramolecular hydrogen bond (IMHB) responsible for the planarity of the molecule. In both compounds the molecules form chains through NH…O (compound 2) and OH…N hydrogen bonds (compound 5) but giving rise to the same packing mode. Ab initio calculations (6–31G∗∗) have been carried out on both compounds in order to study the effect of the IMHB on the structure.

The crystal and molecular structures of five 3(5)-amino-5(3)-arylpyrazoles differing in the nature of the substituent at the para position of the phenyl ring (1: X = H; 3.H2O: X = OCH3; 4: X = Cl; 5: X = Br and 6: X = NO2) have been determined by X-ray analysis. Three situations were detected in the crystal structures: the 3-tautomer is present in 1, 3 and 4; the 5-tautomer is only found in 6 and both tautomers (1:1) are observed in 5. The crystal packings are governed by NH… N O hydrogen bonds and also by OH…N interactions in the monohydrate of 3. It is worth noting that in 1, 3, 4 and 5 there are N-H…π(arene) contacts that might play a role in stabilizing the packing. Solid state 13C NMR results are consistent with the above crystallographic conclusions, thus allowing to determine that the only compound for which no good crystals have been obtained, the p-methyl derivative 2 should be a 3-amino tautomer. NMR solution studies (1H and 13C) allow to determine the 3-amino/5-amino tautomeric equilibrium constant, KT, which obeys a Hammett relationship with σp. Geometry optimizations of the 3 and 5-tautomers at semi-empirical level (AM1) were performed. In all compounds, the 3-tautomer has been found to possess a relatively lower energy by approximately 2 kcal mol−1. The potential energy surface as a function of the hybridization of the amino group and its conformation have also been analyzed.

Significant information on the structure of various bisazolium salts of the type CA2 (C++ 2A−) were revealed by the study of the FAB spectra of their positive and negative ions. Thus only one spectrum, whatever it consists of the positive or of the negative ions spectrum, enables the identification of the cation C++ and of the anion A−. Moreover, the same information are collected from the CAD spectrum of the adduct ion CA+ allowing the identification of such a compound in a mixture.

Several 5,6,12,13-tetrahydrobispyrazolo[1,2-a:1′,2′-e][1,2,5,6] tetraazocinediium dihalides 4a–d and 8 are prepared from pyrazole, 3,5-dimethylpyrazole, 4-(1-adamantyl)pyrazole and campho[2,3-c]pyrazole by stepwise alkylation with 1,2-dibromoethane or 1,2-dichloroethane. Their structural characterization has been achieved by NMR and mass spectrometry. Dynamic NMR spectroscopy allowed the measurement of the barrier for the chair–chair interconversion in the case of the parent compound 4a and the 1,3,8,10-tetramethyl derivative 4b. These barriers as well as the preferred chair conformation are rationalized through semi-empirical and molecular mechanics calculations with regard to dibenzo[a,e]cycloocta-1,5-diene. The study of doubly charged bispyrazolium salts allows demonstration of their reduction by addition of a hydride ion [C+++ H–→(C + H)+] during FABMS experiments.

The structure and properties (crystallography, NMR, theoretical calculations) of the three N-unsubstituted benzazoles (1H-benzimidazoles, 1H- and 2H-indazoles, 1H- and 2H-benzotriazoles) have been reviewed for the period 2000-2012 with some results from previous years. The study of these compounds will greatly increase in the coming years and it is expected that the present review will contribute to it.

The carbon-13 chemical shifts and coupling constants of 1168 pyrazoles are reported, some of them in several solvents. These data are briefly discussed on the basis of statistical treatment and qualitative comparisons.

Reaction of NH-pyrazoles with 1-bromoadamantane in a high pressure stainless steel autoclave (250 ml, maximum working pressure of 200 atm) gives regioselectively 1-adamantyl or 4-adamantylpyrazoles depending on the temperature.

Reaction of NH-pyrazoles with 1 -bromoadamantane in a high pressure stainless steel autoclave gives regioselectively 1-(1 -adamantyl)or 4-(1-adamantyl)pyrazoles depending on the temperature. A series of cross-experiments allows to establish the mechanism of this reaction. The molecular structure of the most simple derivative, 4-(1-adamantyl) pyrazole (3a), has been determined. Intermolecular N−H...N hydrogen bonds hold the four independent molecules together in a helix system parallel to the c axis. The crystal is built up of two centrosymmetrically related helices

The crystal and molecular structures of five 3(5)-amino-5(3)-arylpyrazoles differing in the nature of the substituent at the para position of the phenyl ring (1: X = H; 3.H2O: X = OCH3; 4: X = Cl; 5: X = Br and 6: X = NO2) have been determined by X-ray analysis. Three situations were detected in the crystal structures: the 3-tautomer is present in 1, 3 and 4; the 5-tautomer is only found in 6 and both tautomers (1:1) are observed in 5. The crystal packings are governed by NH… N O hydrogen bonds and also by OH…N interactions in the monohydrate of 3. It is worth noting that in 1, 3, 4 and 5 there are N-H…π(arene) contacts that might play a role in stabilizing the packing. Solid state 13C NMR results are consistent with the above crystallographic conclusions, thus allowing to determine that the only compound for which no good crystals have been obtained, the p-methyl derivative 2 should be a 3-amino tautomer. NMR solution studies (1H and 13C) allow to determine the 3-amino/5-amino tautomeric equilibrium constant, KT, which obeys a Hammett relationship with σp. Geometry optimizations of the 3 and 5-tautomers at semi-empirical level (AM1) were performed. In all compounds, the 3-tautomer has been found to possess a relatively lower energy by approximately 2 kcal mol−1. The potential energy surface as a function of the hybridization of the amino group and its conformation have also been analyzed.

The crystal and molecular structure of [14]paracyclo-bis-(1,2)pyrazoliumphane dibromide (1a) has been determined. The compound exists in the solid state in the chair (C) conformation while both chair (C) and boat (B) conformations are present in solution in comparable amounts. The barrier to the C ⇌ B interconversion has been determined by 1H NMR spectroscopy ( ΔG ‡ ≈ 17 kcal mol −1 ). AM1 semiempirical calculations conveniently reproduce the difference in stability between the chair (C) and the boat (B) conformations. [14]Paracyclo-bis-(1,2)pyrazolium-phane dibromide exists in the solid state in the chair conformation (X-ray crystallography) while both chair and boat conformations are present in solution in comparable amounts. The barrier to the chair boat interconversion has been determined by 1H NMR spectroscopy ( ΔG‡ ≈ 17 kcal mol −1 ).

A computational study of the structural and thermochemical properties of N-phenyl (open) and N-alkyl (cyclic) ureas, through the use of M05-2X and B3LYP density functional theory calculations has been carried out. The consistency of the literature experimental results has been confirmed, and using mainly isodesmic reactions, the unknown ΔfH0(g) of the other urea derivatives were estimated. The experimental results together with the theoretical information have permitted the study of the effect of phenyl, p- and m-chlorophenyl, alkyl, and carbonyl substitutions on the thermodynamical stability of urea and its cyclic derivatives. The peculiar behavior of the N-tert-butyl substituent in cyclic ureas has been related to geometric deformations. © 2010 American Chemical Society.

Thermochemical and thermophysical studies have been carried out for crystalline 3,4,4′-trichlorocarbanilide. The standard (p° = 0.1 MPa) molar enthalpy of formation, at T = 298.15 K, for the crystalline 3,4,4′-trichlorocarbanilide (TCC) was experimentally determined using rotating-bomb combustion calorimetry, as -(234.6 ± 8.3) kJ · mol-1. The standard enthalpy of sublimation, at the reference temperature of 298.15 K, was measured by the vacuum drop microcalorimetric technique, using a High Temperature Calvet Microcalorimeter as (182.1 ± 1.7) kJ · mol-1. These two thermochemical parameters yielded the standard molar enthalpy of formation of the studied compound, in the gaseous phase, at T = 298.15 K, as -(52.5 ± 8.5) kJ · mol-1. This parameter was also calculated by computational thermochemistry at M05-2X/6-311++G** and B3LYP/6-311++G(3df, 2p) levels, with a deviation less than 4.5 kJ · mol-1 from experimental value. Moreover, the thermophysical study was made by differential scanning calorimetry, DSC, over the temperature interval between T = 263 K and its onset fusion temperature, T = (527.5 ± 0.4) K. A solid-solid phase transition was found at T = (428 ± 1) K, with the enthalpy of transition of (6.1 ± 0.1) kJ · mol-1. The X-ray crystal structure of TCC was determined and the three-centred N-H⋯O{double bond, long}C hydrogen bonds present analyzed. © 2009 Elsevier Ltd. All rights reserved.

The behavior in solution and in the solid state of 3(5)-phenyl-1H-pyrazole (7), 3(5)-phenyl-4-chloro-1H-pyrazole (6), 3(5)-phenyl-4-bromo-1H-pyrazole (1), and 3(5)-p-chlorophenyl-4-bromo-1H-pyrazole (8) is discussed in relation to their 3-phenyl (a)/5-phenyl (b) annular tautomerism. Two new X-ray structures are reported: a new polymorph of 1 and the structure of 6. The new polymorph is a 3-phenyl-1H-pyrazole 1a′ trimer while the new structure is a 5-phenyl-1H-pyrazole 6b trimer. The combined use of NMR at low temperature and DFT calculations allows to discuss the tautomerism of the first three pyrazoles and to predict that the fourth one should be a tetramer formed by both tautomers, 8a and 8b. © 2010 Elsevier B.V. All rights reserved.

The experimental gas-phase proton affinities (PAs) of 32 N-H and N-methyl pyrazoles have been determined by means of Fourier transform ion cyclotron resonance spectrosccopy (FTICR). Together with the previously reported PAs for 12 C-methyl-substituted pyrazoles, they provide a set of 57 data (counting each tautomer separately). The remarkably large spread of PAs, ca. 55 kcal.mol -1 , makes this set most suitable for structural analyses

The 13C chemical shifts and some 1H13C coupling constants of twelve N-arylpyrazoles are reported. The assignments were made by using the effects of a fluorine substituent and two-dimensional techniques.

Seven N-unsubstituted curcuminoid pyrazoles have been synthesized from the corresponding β-diketones (including curcumin). We evaluated the possibility of curcuminoid pyrazoles regulating the activity of matrix metalloproteinases (MMPs) by human intestinal epithelial cells in vitro. Zymographic analysis revealed that three compounds significantly down-regulated MMP-9 activity on inflammation-induced intestinal epithelial cells, making them original candidates for the treatment of inflammatory bowel disease (IBD). © 2008 Elsevier Ltd. All rights reserved.

Using data from this work and from the literature, the standard free-energy changes for reactions i and ii, AG,+(g) and AGo12(soln), are compared: B(g) + H+(g) ~2 BH+(g) (i); B(soln) + 12(soln) s B...12(soln) (ii). Bs are S(sp3) and N(sp2 and sp') n-donor bases (all compounds for which data sets are extensive and reliable), spanning a range of AGH+(g) of ca. 65 kcal-mol-I. Within families, AGH+(g) and AGol,(soln) are linearly related. Thus, a pattern of reactivity similar to that prevailing in the gas phase can be found in acid-base reactions in solution, provided charge dispersal through hydrogen bonding to the solvent is minimized.

The 13 C chemical shifts and the 1 J ( 1 H- 13 C) coupling constants of the title compounds are relatively sensitive to solvent effects (Δδ = 2–3 ppm, Δ J = 2–3 Hz), deuterochloroform values being near the averaged ones (11 solvents). The solvent induced shifts of the three heterocyclic carbons and those of the N -methyl groups are discussed using the Kamiet—Taft—Abboud formalism. As solvent (pure liquid) 1-methylimidazole appears as a highly dipolar-polarizable solvent

The intrinsic basicity of 24 azoles (pyrazoles, indazoles, imidazoles, benzimidazoles) and 7-methylazaindole was determined by mass spectrometry techniques, ion cyclotron resonance (ICR) and/ or chemical ionization (CI) in conjunction with tandem mass spectrometry (MS/MS). A reasonably good agreement (r 2 =0.967) is found between both methods (15 compounds). Thus, it is possible to use CI/MS/MS to determine the intrinsic basicity of compounds not measurable by ICR for purity or volatility reasons. Some anomalies are interpreted in terms of entropy and steric effects. The basicity data are also discussed by using empirical models (σα, σ R ) and chelation and annelation effects

A thermophysical and thermochemical study has been carried out for crystalline imidazolidin-2-one and N,N′-trimethyleneurea [tetrahydropyrimidin-2(1H)-one]. The thermophysical study was made by differential scanning calorimetry, d.s.c., in the temperature intervals between T = 268 K and their respective melting temperatures. Several solid–solid transitions have been detected in imidazolidin-2-one. The standard (p∘ = 0.1 MPa) molar enthalpies of formation, at T = 298.15 K, for crystalline imidazolidin-2-one and N,N′-trimethyleneurea [tetrahydropyrimidin-2(1H)-one], were determined using static-bomb combustion calorimetry. The standard molar enthalpies of sublimation, at T = 298.15 K, for the two compounds were derived from the variation of their vapour pressures, measured by the Knudsen effusion method, with the temperature. These two thermochemical parameters yielded the standard molar enthalpies of formation of the two cyclic urea compounds studied in the gaseous phase at T = 298.15 K. These values are discussed in terms of molecular structural contributions and interpreted on the bases of the “benzo-condensed effect” and of the ring strain of imidazolidin-2-one., Thanks are due to Gabinete de Relações Internacionais da Ciência e do Ensino Superior (GRICES), Lisbon, Portugal, and Consejo Superior de Investigaciones Científicas (CSIC), Madrid, Spain for a joint research project GRICES/CSIC. Thanks are due to Fundação para a Ciência e a Tecnologia, F.C.T., Lisbon, Portugal, and to FEDER for financial support to Centro de Investigação em Química da Universidade do Porto (CIQ-U.P.). V.L.S.F. thanks Faculdade de Ciências for a research grant. The Spanish co-authors gratefully acknowledged the support of DGES/MEC (CTQ 2006-02586, CTQ 2006-12745/BQU, CTQ 2006-10178/BQU).

Molecular crystals of 2-phenylbenzimidazole, C13H 10N2, exhibit a one-dimensional incommensurate structure. The structure has been solved by charge flipping and refined using the superspace formalism in the (3 + 1) D superspace group C2/c(0b0) s0 with modulation wave-vector q = 0.368b*. The unit cell contains 8 molecules, each one disorderly occupying two configurations related by inversion center. The refinement based on a molecular model with two rigid-body parts per molecule includes up to second order Fourier amplitudes for the modulation. The displacive modulation involves a significant intra-molecular twist between the phenyl and the benzimidazole parts. © by Oldenbourg Wissenschaftsverlag.