Electron density distribution in heterocyclic systems with two adjacent nitrogen atoms

The dipole moments of 19 pyrazole derivatives are determined. Comparing measured dipole moments with those calculated by vector addition, differences in polarization of the pyrazole ring are considered as functions of the natures and positions of substituents. The inadequacy of a symmetrical structure for pyrazole, with a hydrogen linked to both nitrogens, is demonstrated. Comparison of experimentally determined dipole moments with those calculated by the vector method makes it possible to choose between tautomeric structures of 3,4-dibromopyrazole.For Part IV see [1].     

Dipole moments of molecules of 1, 3, 5-triaryl-δ2-pyrazolines

The dipole moments of 1, 3, 5-triphenylpyrazole and a number of pyrazoline derivatives are determined. The presence of a C=C double bond in pyrazole does not lead to formation of a single electron system in the heterocyclic ring. Comparison of found and calculated vector dipole moments confirms the appreciable effect of aromatic groups at position 1, and especially at position 3, and the slight effect at position 5.     

Electron density distribution in heterocyclic systems with two adjacent nitrogen atoms

Dipole moments found are compared with those calculated vectoran ially. Bis(3, 5-dimethylpyrazol-4-yl) has a constant dipole moment, which indicates inequality of nitrogen atoms in the pyrazole ring. Dipole moments of condensed pyrazolopyridines can be found by adding vectorially the dipole moments of pyridine and pyrazole. Involvement of a nitrogen atom and formation of two aromatic rings does not significantly alter the dipole moment of pyrazolo[2, 3-a]-pyridine as compared with pyrazole.For Part V see [1].     

Electron-density distribution and reactivities of ethynylimidazoles and -pyrazoles

The electron shells of imidazole, pyrazole, and their ethynyl derivatives were calculated by the CNDO/2 method (complete neglect of differential overlap). The dipole moments, ionization potentials, and energies of heterolytic cleavage of the CH bonds of the ethynyl groups were calculated. The results are compared with the experimental data on the reactivities and acidities. The ethynyl substituent is a weak electron acceptor. The donor capacity of the ring correlates with the charges on the corresponding carbon atoms. The 4 and 5 positions of imidazole constitute an exception to this. The energy of heterolytic cleavage of the CH bond decreases as the electronic charge on the ethynyl group increases.     

Studies of pyrazoles. XLVI. Synthesis of pyrazolo pyridones

Cyclizations of acetoacetamidopyrazoles and of appropriate aminopyrazole crotonates to pyrazolopyridines with a hydroxy group in the pyridine ring are effected. In the case of an amino group at position 5 in the pyrazole ring cyclization takes place with acetylacetone. It is shown that the structure of pyrazolopyridone put forward by Bülow is incorrect.     

Ruthenium-catalyzed C-H/CO/Olefin coupling reaction of N-arylpyrazoles. Extraordinary reactivity of N-arylpyrazoles toward carbonylation at C-H bonds

The reaction of 1-arylpyrazoles with CO and ethylene in the presence of Ru(3)(CO)(12) resulted in regioselective carbonylation at the ortho C-H bonds. While it is found that the pyrazole ring also functions as the directing group for C-H bond cleavage, the efficiency of the reaction depends on the position of the pyrazole ring.     

Design, synthesis, and biological evaluation of novel alkenylthiophenes as potent and selective CB1 cannabinoid receptor antagonists

A novel class of (5-(pent-1-enyl)thiophen-2-yl)pyrazole antagonists was discovered, many of which exhibited potent CB1 activity and good CB1/2 selectivity, suggesting that along with a 1,3-transposition of the carbonyl of the pyrazole 3-carboxamide, bioisosteric replacement of the conventional pyrazole 5-aryl group with a thienyl ring substituted with an appropriate alkenyl moiety is viable.     

Amino acid catalyzed reactions. A facile route to some heteroarylbispyrazoles

This newly designed route assembled a pyrazole ring with an aldehydic functionality over another pyrazole moiety. Further, formyl group was exploited in different routes such as condensation reactions, imidazole and pyrimidone/thione synthesis. The present reactions were performed with glycine, a facile catalyst, and the results were compared well with those of conventional methods.     

Mass spectra and structure of halo-substituted 2- and 4-aminopyrimidines

The mass spectra of methyl- and halo-substituted 2- and 4-aminopyrimidines at an ionizing electron energy of 70 eV were studied. It is shown that the molecular ion of the investigated compounds corresponds primarily to the imine form. This structure determines the principal direction of disintegration, which proceeds through the formation of pseudomolecular ions with an imidazole or pyrazole structure, depending on the position of the amino group in the pyrimidine ring.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 12, pp. 1689–1693, December, 1973.     

A single crystal X-Ray diffraction analysis of 1,9-dihydro[1] benzothiopyrano[4,3-c] pyrazole 5,5-dioxide

The structure of 1,4-rlihydro[1 ]benzothiopyrano[4,3-c ]pyrazole 5,5-dioxide was determined by single crystal x-ray diffraction. The molecule crystallizes in space group P2₁/c with a = 13.4378(6), b = 5.5938(3), c = 12.9837(6)Å, and β = 103.831°. The final R value is 0.083. Surprisingly, the tautomer with N(2)-H exists in the crystal with the pyrazole ring being planar. The entire system is not planar as the benzene ring is rotated about C(9a) and C(9b) with respect to the pyrazole ring. In the crystal structure the pyrazole exists as hydrogen-bonded dimers with two molecules related by a center of symmetry.     

Theoretical studies on geometry,solvent effect,and photochromic mechanism of two bis‐heterocyclic compounds containing pyrazolone ring

Two bis‐heterocyclic compounds containing pyrazolone ring, 1‐phenyl‐3‐methyl‐4‐(6‐hydro‐4‐amino‐5‐sulfo‐2,3‐pyrazine)‐pyrazole‐5‐one and 1‐phenyl‐3‐methyl‐4‐(6‐hydro‐4‐methylamino‐5‐sulfo‐2,3‐pyrazine)‐pyrazole‐5‐one, are investigated to gain a deeper insight into their geometries and photochromic mechanism by applying density functional theory. The solvent effects are simulated using the polarizable continuum model of the self‐consistent reaction field theory. Bader's atom‐in‐molecule theory is used to investigate the nature of hydrogen bonds. The data of energy, dipole moments, and the condensed Fukui functions have been calculated to assess the stability and reactivity of the title compounds. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010     

Conformations of highly hindered aryl ethers: IX. Dipole moment evidence for an intramolecular donor-acceptor complex

In a search for evidence that a π cloud proximal halogen interaction is of importance to the mode of action of the thyroid hormones, the dipole moments of the 1'-naphthyl (I), (4.29 D), 4'-carboxymethylphenyl (II), (2.90 D), 2'-bromo4'-carboxymethylphenyl (III), (3.56 D), and methyl (IV), (3.24 D) ethers of 2,4dinitro-6-bromophenol were determined in benzene at 25 °C. The moments of (I), (II) and (III) are approximated best by those calculated for the twisted conformation in which the bromine closely approaches the face of the other ring. That of the naphthyl ether (I) can, however, be explained only by inclusion of an intramolecular electron donor-acceptor charge-transfer moment of 1.6 D directed from the π cloud of the naphthyl ring to the proximal nitro group of the other ring, or of 2.8 D to the proximal bromine of that ring. In the preferred conformation of the methyl ether (IV), the methoxy group is coplanar with the ring while the 2-nitro group is twisted 90° from coplanarity to accomodate it. A mesomeric moment of 2.3 D is estimated from this for the 2,4-dinitro-6-bromophenoxy moiety and is used in calculating the expected moments of the other ethers.     

Poly condensed nitrogen heterocycles. V. Two novel ring systems: Pyrazolo[5,1-c]-1,2,4-thiadiazine and pyrazolo[3,4-c]-1,2-thiazine

The title compounds were obtained by reaction of aminopyrazoles IV and VII with ω-acetophenonesulfonyl chloride (II, R = C₆H₅). In agreement with the general pattern of the distribution of electron density in the pyrazole nucleus, this work confirms that the position 4 of ring is the favoured site of electrophilic attacks.     

Dipole moments of some isoxazole derivatives

The dipole moments of isoxazole and 13 of its halo, amino, and nitro derivatives were measured. A method is proposed for vector calculation for estimating the direction of the dipole moment of the isoxazole ring. It is demonstrated that phenyl substituents in the 3 and 5 positions are electron donors with respect to the isoxazole ring. It was found that the dipole moments of 4-substituted 3,5-dimethylisoxazoles correlate satisfactorily with the Hammett constants.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 4, pp. 460–463, April, 1972.     

Hetarylpyrazoles. II. Reactions of pyrazol-l'-ylpyridines

Pyrazol-l'-ylpyridines undergo electrophilic substitution reactions (bromination, chlorination, and nitration) preferentially in the pyrazole ring. There is some evidence of the mutual influence of the pyrazole and the pyridine ring on the reactivity of the system. Some modifications of the substituents were also carried out. A dihydro derivative of a new ring system, pyrazolo[1′,2′-a]pyrido[2,1-c][l,2,4]triazine was also obtained.     

Comparison of the molecular interactions of 7′-carboxyalkyl apigenin derivatives with S. cerevisiae α-glucosidase

As one of the most investigated flavonoids, apigenin, is considered to be a strong α-glucosidase inhibitor. However, the clinical utility of apigenin is limited due to its low solubility. It was reported that the solubility and biological activity can be improved by introducing sole carboxyalkyl group into apigenin, especially the 7′-substitution. With the increase of length of the alkyl chain in carboxyalkyl group, B ring of the apigenin derivative is embedded much more deeply into the binding cavity while the carboxyalkyl stretches to the neighboring cavity. All of the terminal carboxyl groups form hydrogen bonding interactions easily with the surrounding polar amino acids, such as His239, Ser244, Arg312 and Asp349. Thus, the electron density values of the carbonyl in the carboxyl group become higher than the solution status due to the strong molecular interactions. In fact, electron densities of most of the chemical bonds are decreased after molecular docking procedure. On compared with the solution phase, however, dipole moments of most of these molecules are increased, and their vectors are reoriented distinctly in the active sites. It is noticed that all of the Highest Occupied Molecular Orbital (HOMO) and Lowest Unoccupied Molecular Orbital (LUMO) are distributed throughout the whole parent apigenin ring in solution phase, whereas the disappeared situation happened on the B rings of some molecules (II–IV) in the active site, leading to higher energy gaps.     

Diels-alder cycloadditions of 1,3,4,-oxadiazin-6-ones with electron rich pi systems

A study of the cycloaddition behavior of several 2,5-disubstituted 1,3,4-oxadiazin-6-ones with electron rich pi bonds has been carried out. $\text{trans}$-1-Propenylpyrrolidine was found to react with the oxadiazinone ring system to give rise to a ring opened diazatrienyl substituted carboxylic acid. Further heating of the acid results in decarboxylation, hydrolysis, cyclization and pyrrolidine elimination to produce a disubstituted pyrazole. Reaction with the trisubstituted enamine 1 - ( 2 - methyl-propenyl) pyrrolidine, was also studied in some detail. The cycloadditions encountered can be rationalized as proceeding by an initial Diels-Alder reaction followed by cheletropic extrusion of nitrogen to produce a ketoketene intermediate. The fate of the ketene is markedly dependent upon the overall pattern of substitution. Some of the products formed can be explained in terms of a competitive migration of the pyrrolidino group to the ketene and benzoyl groups. With one system the major cycloadduct is derived from the Diels-Alder reaction of a transient azaketene tautomer formed by an electrocyclic opening of the oxadiazinone ring.     

Oxidation of pyrazoles containing the 2-hydroxyethyl group on a NiO(OH) electrode in aqueous alkali

The electrooxidation of pyrazoles containing hydroxyethyl group bound with the pyrazole ring at its N and C atoms (1-(2-hydroxyethyl)pyrazole and (4-(2-hydroxyethyl)pyrazole, respectively) in an undivided cell on a NiO(OH) electrode in aqueous alkali is studied. The oxidation of 1-(2-hydroxyethyl)pyrazole is shown to result in the formation of pyrazole-1-acetic acid with a yield of 80.0%. In the case of 4-(2-hydroxyethyl)pyrazole the process proceeds more exhaustively, leading to the formation of pyrazole-4-carboxylic acid as the major product with a yield of 57.0%. The regularities of these processes are discussed.     

Reaction of 4-cyano-5-aminopyrazole and 3,4-dicyano-5-aminopyrazole with dimethylformamide diethylacetal

The condensation of 4-cyano-5-aminopyrazole or 3,4-dicyano-5-aminopyrazole with dimethylformamide diethylacetal was studied. It was shown that, in addition to the formation of dimethylaminomethyleneamino derivatives, alkylation of the pyrazole ring occurs under severe conditions without a solvent. Only the corresponding formamidino derivatives are formed when the same reactions are carried out in methanal under milder conditions. The site of addition of an ethyl group to the pyrazole ring in the N-alkyl derivatives obtained was established by ¹³C NMR and PMR spectroscopy. The possibility of the synthesis of 4-amino- or 4-methylmercaptopyrazolo[3,4-d]pyrimidines by cyclization of the corresponding dimethylamino- methyleneaminopyrazoles with a cyano group in the ortho position was demonstrated for the first time.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 259–264, February, 1984.     

Substituent control of hydrogen bonding in palladium(II)-pyrazole complexes

Inter- and intramolecular hydrogen bonding of an N-H group in pyrazole complexes was studied using ligands with two different groups at pyrazole C-3 and C-5. At C-5, groups such as methyl, i-propyl, phenyl, or tert-butyl were present. At C-3, side chains L-CH(2)- and L-CH(2)CH(2)- (L = thioether or phosphine) ensured formation of chelates to a cis-dichloropalladium(II) fragment through side-chain atom L and the pyrazole nitrogen closest to the side chain. The significance of the ligands is that by placing a ligating side chain on a ring carbon (C-3), rather than on a ring nitrogen, the ring nitrogen not bound to the metal and its attached proton are available for hydrogen bonding. As desired, seven chelate complexes examined by X-ray diffraction all showed intramolecular hydrogen bonding between the pyrazole N-H and a chloride ligand in the cis position. In addition, however, intermolecular hydrogen bonding could be controlled by the substituent at C-5: complexes with either a methyl at C-5 or no substituent there showed significant intermolecular hydrogen bonding interactions, which were completely avoided by placing a tert-butyl group at C-5. The acidity of two complexes in acetonitrile solutions was estimated to be closer to that of pyridinium ion than those of imidazolium or triethylammonium ions.