Cyclization of arylhydrazones of cross-conjugated enynones: synthesis of luminescent styryl-1H-pyrazoles and propenyl-1H-pyrazoles.

Condensation of 1,5-disubstituted pent-1-en-4-yn-1-ones with arylhydrazines in acidified alcohol results mainly in the formation of the corresponding arylhydrazones with traces of the side products of cyclization at the double bond - 1,5-diaryl-3-(arylethynyl)-4,5-dihydro-1H-pyrazoles (pyrazolines). Arylhydrazones are cyclized only by refluxing in high-boiling polar solvents (DMF and ethylene glycol), with the selective formation of 1,5-disubstituted 3-styrylpyrazoles in up to 77-95% yields. Thermodynamically, the cyclization of arylhydrazones at the triple bond is the most preferable pathway, as shown by DFT calculations and preparative synthesis experiments. Thus, we demonstrate that the reactions of arylhydrazines with 1,5-disubstituted pent-1-en-4-yn-1-ones lead to the formation of arylhydrazones and side pyrazoline impurities in a parallel (not consecutive) manner. 2-Hydrazinylpyridine interacts with 1,5-disubstituted pent-1-en-4-yn-1-ones in some other way, giving not pyridinylhydrazones but 2-(5-styryl-3-phenyl-1H-pyrazol-1-yl)pyridines (despite the acidity of the medium). The authors have developed a gram-scale synthesis method for these compounds, which were obtained in up to 60-82% yields. Besides, we have developed the synthesis method for certain styrylpyrazoles, which are quite promising substances for use as fluorescent probes. Their spectral-luminescence characteristics were examined as well as their complexing with Hg2+, Cd2+, and Pb2+ ions.

Ketone Derivatives of Propargylamines as Synthetic Equivalents of Conjugated 2,4,1-Enynones in the Synthesis of Acetylenic 2-Pyrazolines and Pyrazoles.

An interaction of 1,5-diaryl-3-X-pent-4-yn-1-ones (where X stands for piperidin-1-yl, morpholin-4-yl, 4-methylpiperazin-1-yl) with arylhydrazines proceeds at room temperature and results in 3-aryl-5-arylethynyl-1-phenyl-4,5-dihydro-1H-pyrazoles with up to 57-73% yields. Under similar conditions, the cyclocondensation of conjugated 2,4,1-enynones with arylhydrazine proceeds only in the presence of cyclic amines. 1,5-Diaryl-3-X-pent-4-yn-1-ones are reported as synthetic equivalents of conjugated 2,4,1-enynones in reactions with arylhydrazines. On the basis of obtained data, there are highly efficient methods developed for the synthesis of 5-arylethynyl-substituted 4,5-dihydro-1H-pyrazoles, as well as for similarly structured 1H-pyrazoles prepared by oxidation in AcOH. Presented products possess quite marked fluorescent abilities. Emission maximum wavelengths are located at 453-465 and 363-400 nm, respectively; certain compounds show extremely large Stokes shifts that may reach 91,000 cm-1.

Michael Addition of 3-Oxo-3-phenylpropanenitrile to Linear Conjugated Enynones: Approach to Polyfunctional δ-Diketones as Precursors for Heterocycle Synthesis.

Reaction of linear conjugated enynones, 1,5-diarylpent-2-en-4-yn-1-ones [Ar1C≡CCH=CHC(=O)Ar2], with 3-oxo-3-phenylpropanenitrile (NCCH2COPh) in the presence of sodium methoxide MeONa as a base in MeOH at room temperature for 4-26 h affords polyfunctional δ-diketones as a product of regioselective Michael addition to the double carbon-carbon bond of starting enynones. The δ-diketones have been formed as mixtures of two diastereomers in a ratio of 2.5:1 in good general yields of 53-98%. A synthetic potential of the obtained δ-diketones has been demonstrated by heterocyclization with hydrazine into substututed 5,6-dihydro-4H-1,2-diazepine.

Reactivity of Cross-Conjugated Enynones in Cyclocondensations with Hydrazines: Synthesis of Pyrazoles and Pyrazolines.

The cyclocondensation of cross-conjugated enynones, dienynones, and trienynones (easily available due to low-cost starting compounds) with arylhydrazines leads to the regioselective synthesis of pyrazole derivatives (dihetaryl-substituted ethens, buta-1,3-diens, and hexa-1,3,5-triens) or results in 4,5-dihydro-1H-pyrazoles in good yield. The reaction path is controlled by the character of the substituent in enynone: the pyrazoles are obtained from the reaction of substrates that contain five-membered heteroaromatic substituents with arylhydrazines, and the 4,5-dihydro-1H-pyrazoles are obtained from the reaction of 1,5-diphenylpent-1-en-4-yn-3-one with arylhydrazines consistently. Despite the presence of a substituent, cyclocondensation of 2-hydrazinylpyridine with all of examined cross-conjugated enynones leads to the formation of pyrazoles. The reaction does not require special conditions (temperature, catalyst, inert atmosphere). The cyclocondensation pathways are determined by the electronic effect of an electron-rich five-membered heteroaromatic ring in the substrate. The synthesis allows use of various substituents and functional groups in enynone and hydrazine. The present method features high yields and simplicity of the product purification. The obtained pyrazoles possess fluorescent properties with a quantum yield up to 31%.

Stereoselective Synthesis of Multisubstituted Cyclohexanes by Reaction of Conjugated Enynones with Malononitrile in the Presence of LDA.

Reaction of linear conjugated enynones, 1,5-diarylpent-2-en-4-yn-1-ones, with malononitrile in the presence of lithium diisopropylamide LDA, as a base, in THF at room temperature for 3-7 h resulted in the formation of the product of dimerization, multisubstituted polyfunctional cyclohexanes, 4-aryl-2,6-bis(arylethynyl)-3-(aryloxomethyl)-4-hydroxycyclohexane-1,1-dicarbonitriles, in yields up to 60%. Varying the reaction conditions by decreasing time and temperature and changing the ratio of starting compounds (enynone and malononitrile) allowed isolating some intermediate compounds, which confirmed a plausible reaction mechanism. The relative stability of possible stereoisomers of such cyclohexanes was estimated by quantum chemical calculations (DFT method). The obtained cyclohexanes were found to possess photoluminescent properties.

Crystal structures of (E)-5-(4-methyl-phen-yl)-1-(pyridin-2-yl)pent-2-en-4-yn-1-one and [3,4-bis(phenyl-ethyn-yl)cyclo-butane-1,2-di-yl]bis-(pyridin-2-yl-methanone).

Recrystallization of (E)-5-phenyl-1-(pyridin-2-yl)pent-2-en-4-yn-1-one at room temperature from ethyl-ene glycol in daylight afforded [3,4-bis-(phenyl-ethyn-yl)cyclo-butane-1,2-di-yl)bis-(pyridin-2-yl-methanone], C32H22N2O2 (3), while (E)-5-(4-methyl-phen-yl)-1-(pyridin-2-yl)pent-2-en-4-yn-1-one, C17H13NO (2), remained photoinert. This is the first experimental evidence that pentenynones can be photoreactive when fixed in nearly coplanar parallel positions. During the photoreaction, the bond lengths and angles along the pentenyne chain changed significantly, while the disposition of the pyridyl ring towards the keto group was almost unchanged. The cyclo-butane ring adopts an rctt conformation.

Peculiarities of supramolecular organization of cyclic ketones with vinylacetylene fragments.

1,5-Diaryl(heteroaryl)pentenynones show a tendency to crystallize in acentric space groups due to their inclination to form C-H...O hydrogen-bonded chains instead of dimers and thus exhibit nonlinear optical properties. A series of symmetrical α,α'-bis(3-arylprop-2-yn-1-ylidene)cycloalkanones and unsymmetrical α-(furan-2-ylmethylene)-α'-(3-arylprop-2-yn-1-ylidene)cyclohexanones closely related to pentenynones was synthesized, namely 2,5-bis(3-phenylprop-2-yn-1-ylidene)cyclopentanone, C23H16O, 2,5-bis[3-(4-bromophenyl)prop-2-yn-1-ylidene]cyclopentanone, C23H14Br2O, 2,6-bis(3-phenylprop-2-yn-1-ylidene)cyclohexanone, C24H18O, 2,6-bis[3-(4-bromophenyl)prop-2-yn-1-ylidene]cyclohexanone, C24H16Br2O, 4-tert-butyl-2,6-bis(3-phenylprop-2-yn-1-ylidene)cyclohexanone, C28H25O, 4-tert-butyl-2,6-bis[3-(4-methylphenyl)prop-2-yn-1-ylidene]cyclohexanone, C30H30O, 2-(furan-2-ylmethylene)-6-(3-phenylprop-2-yn-1-ylidene)cyclohexanone, C20H16O2, and 6-(3-butylprop-2-yn-1-ylidene)-2-(furan-2-ylmethylene)cyclohexanone, C10H20O2, and investigated by means of X-ray diffraction to understand peculiarities of their supramolecular organization. Four of the eight novel compounds crystallize in acentric space groups. Three of these four compounds contain substituents at the para position of the phenyl ring, which affect the charge density on the H(CPh) atoms and thus stabilize CPh-H...O interactions. The fourth compound realizes the C-H...O hydrogen bonding via H atoms of the furyl ring. The applicability and shortcomings of the Full Interaction Map tool to predict the likelihood of C-H...O and C-H...Br hydrogen-bonded motifs, and the effect of substituents on the phenyl ring on the supramolecular architecture are discussed.

Hydroarylation of unsaturated carbon-carbon bonds in cross-conjugated enynones under the action of superacid CF3SO3H or acidic zeolite HUSY. Reaction mechanism and DFT study on cationic intermediate species.

Reactions of cross-conjugated enynones,1,5-diarylpent-1-en-4-yn-3-ones, with arenes in the system TfOH-pyridine or under the action of acidic zeolite HUSY lead regioselectively to products of hydroarylation of the acetylene bond only,1,1,5-triarylpent-1,4-dien-3-ones, in yields up to 98%. These dienones add one more arene molecule to the double carbon-carbon bond in neat TfOH forming 1,1,5,5-tetraarylpent-1-en-3-ones in high yields. Cationic reaction intermediates have been studied by means of DFT calculations to elucidate plausible reaction mechanisms.

Transformations of Conjugated Enynones in the Superacid CF3SO3H. Synthesis of Butadienyl Triflates, Indanones, and Indenes.

Conjugated 1,5-diarylpent-2-en-4-yn-1-ones add the superacid CF3SO3H to the acetylenic bond with formation of the corresponding butadienyl triflates. Under superacidic reaction conditions, these triflates are transformed into indanone or indene derivatives depending on which substituents on the aromatic ring are conjugated with the butadiene fragment. In a less acidic system (10% vol pyridine in CF3SO3H) only the formation of butadienyl triflates takes place. Cationic reaction intermediates were studied by means of NMR and DFT calculations.

Crystal structure of (E)-1-(2,4-di-nitro-phen-yl)-2-[(E)-5-phenyl-1-(p-tol-yl)pent-2-en-4-yn-1-yl-idene]hydrazine.

In the title compound, C24H18N4O4, the plane of the phenyl ring is inclined to those of the toluene ring and the di-nitro-substituted benzene ring by 66.96 (19) and 47.06 (18)°, respectively, while the planes of the two benzene rings are inclined to one another by 36.26 (19)°. There is an intra-molecular N-H⋯O hydrogen bond between the NH group and the O atom of a nitro group, forming an S(6) ring motif. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds and C-H⋯π inter-actions, forming a three-dimensional network. There are also weak π-π inter-actions present involving the phenyl ring and the di-nitro-substituted benzene ring [inter-centroid distance = 3.741 (2) Å].

Crystal structure of (2E,4E)-5-[bis-(2-hy-droxy-eth-yl)amino]-1-(4-chloro-phen-yl)-5-phenyl-penta-2,4-dien-1-one.

In the title compound, C21H22ClNO3, the penta-diene unit is nearly planar [maximum deviation = 0.023 (1) Å], but the carbonyl O atom deviates significantly [by 0.304 (1) Å] from its mean plane, which is twisted with respect to the phenyl and chloro-benzene rings by 71.34 (13) and 46.40 (13)°, respectively. In the crystal, inversion-related molecules are linked by two pairs of O-H⋯O hydrogen bonds, forming chains propagating along [01-1], enclosing R (2) 2(16) and R (2) 2(22) ring motifs. The chains are linked via C-H⋯O hydrogen bonds and C-H⋯π inter-actions into a three-dimensional supra-molecular architecture.

(E,Z)-1-(4-Chloro-phen-yl)-5-phenyl-5-(phenyl-sulfan-yl)penta-2,4-dien-1-one.

The penta-2,4-dien-1-one fragment of the title compound, C23H17ClOS, is twisted by 20.0 (3)°, as measured by the dihedral angle between the planes of the carbonyl group and its attached C atom and the distant C=C double bond and its attached C atom. The 4-chloro-phenyl group forms a dihedral angle of 4.0 (3)° with the adjacent carbonyl group. Conjugation between the phenyl ring and the C=C double bond is absent; the dihedral angle between the phenyl ring and the C-C=C fragment is 34.3 (2)°. In the crystal, mol-ecules are linked via C-H⋯O hydrogen bonds, forming chains parallel to the b-axis direction.