Microwave-Assisted Synthesis of Fluorescent Pyrido[2,3-b]indolizines from Alkylpyridinium Salts and Enaminones

Pyridinium ylides are well recognized as dipoles for cycloaddition reactions. In its turn, the microwave-assisted interaction of N-(cyanomethyl)-2-alkylpyridinium salts with enaminones unexpectedly proceeds as a domino sequence of cycloisomerization and cyclocondensation reactions, instead of a 1,3-dipolar cycloaddition. The reaction takes place in the presence of sodium acetate as base and employs benign solvents. The optical properties of the resulting pyrido[2,3-b]indolizines were studied, showing green light emission with high fluorescence quantum yields.

4-Styrylquinolines from cyclocondensation reactions between (2-aminophenyl)chalcones and 1,3-diketones: crystal structures and regiochemistry

Structures are reported for two matched sets of substituted 4-styrylquinolines which were prepared by the formation of the heterocyclic ring in cyclocondensation reactions between 1-(2-aminophenyl)-3-arylprop-2-en-1-ones with 1,3-dicarbonyl compounds. (E)-3-Acetyl-4-[2-(4-methoxyphenyl)ethenyl]-2-methylquinoline, C21H19NO2, (I), (E)-3-acetyl-4-[2-(4-bromophenyl)ethenyl]-2-methylquinoline, C20H16BrNO, (II), and (E)-3-acetyl-2-methyl-4-{2-[4-(trifluoromethyl)phenyl]ethenyl}quinoline, C21H16F3NO, (III), are isomorphous and in each structure the molecules are linked by a single C—H...O hydrogen bond to form C(6) chains. In (I), but not in (II) or (III), this is augmented by a C—H...π(arene) hydrogen bond to form a chain of rings; hence, (I)–(III) are not strictly isostructural. By contrast with (I)–(III), no two of ethyl (E)-4-[2-(4-methoxyphenyl)ethenyl]-2-methylquinoline-3-carboxylate, C22H21NO3, (IV), ethyl (E)-4-[2-(4-bromophenyl)ethenyl]-2-methylquinoline-3-carboxylate, C21H18BrNO2, (V), and ethyl (E)-2-methyl-4-{2-[4-(trifluoromethyl)phenyl]ethenyl}quinoline-3-carboxylate, C22H18F3NO2, (VI), are isomorphous. The molecules of (IV) are linked by a single C—H...O hydrogen bond to form C(13) chains, but cyclic centrosymmetric dimers are formed in both (V) and (VI). The dimer in (V) contains a C—H...π(pyridyl) hydrogen bond, while that in (VI) contains two independent C—H...O hydrogen bonds. Comparisons are made with some related structures, and both the regiochemistry and the mechanism of the heterocyclic ring formation are discussed.

Regioselective Synthesis of Pyrazolyl-pyrimidine Hybrids of Pharmacological Interest

The regioselective synthesis of twenty novel [3-substituted 5-hydroxy-5-(trifluoromethyl)-4,5-dihydro-1H-pyrazol-1-yl][6-aryl-(2-methylthio)pyrimidin-4-yl]methanones from the cyclocondensation reactions of new 6-aryl-2-(methylthio)pyrimidine-4-carbohydrazides with 4-substituted 1,1,1-trifluorobut-3-en-2-ones is reported. Human acetylcholinesterase (HsAChE) and butyrylcholinesterase (HsBChE) inhibition tests were performed on selected products in order to explore the possible pharmacological applications of these compounds. Two compounds showed significant and selective inhibitory activity for BChE.

PEG mediated synthesis of 6-pyrazinyl-/fused pyrazinylquinazolin-4(3H)-ones using Castro-Stephen coupling, oxidation and cyclocondensation reactions

A PEG-mediated green synthesis of 6-pyrazinyl-/fused pyrazinylquinazolin- 4(3H)-ones was developed starting from 6-iodo-3-methyl-2-phenylquinazolin- 4(3H)-one by means of quinazolinone-based internal alkyne/1,2-diketone as intermediates using the Castro?Stephen coupling reaction/potassium permanganate mediated oxidation and cyclocondensation reactions.

Conversion of substituted 5-aryloxypyrazolecarbaldehydes into reduced 3,4′-bipyrazoles: synthesis and characterization, and the structures of four precursors and two products, and their supramolecular assembly in zero, one and two dimensions

The reaction of 5-chloro-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde with phenols under basic conditions yields the corresponding 5-aryloxy derivatives; the subsequent reaction of these carbaldehydes with substituted acetophenones yields the corresponding chalcones, which in turn undergo cyclocondensation reactions with hydrazine in the presence of acetic acid to form N-acetylated reduced bipyrazoles. Structures are reported for three 5-aryloxycarbaldehydes and the 5-piperidino analogue, and for two reduced bipyrazole products. 5-(2-Chlorophenoxy)-3-methyl-1-phenyl-1H-pyrazole-4-carbaldehyde, C17H13ClN2O2, (II), which crystallizes with Z′ = 2 in the space group P\overline{1}, exhibits orientational disorder of the carbaldehyde group in each of the two independent molecules. Each of 3-methyl-5-(4-nitrophenoxy)-1-phenyl-1H-pyrazole-4-carbaldehyde, C17H13N3O4, (IV), 3-methyl-5-(naphthalen-2-yloxy)-1-phenyl-1H-pyrazole-4-carbaldehyde, C21H16N2O2, (V), and 3-methyl-1-phenyl-5-(piperidin-1-yl)-1H-pyrazole-4-carbaldehyde, C16H19N3O, (VI), (3RS)-2-acetyl-5-(4-azidophenyl)-5′-(2-chlorophenoxy)-3′-methyl-1′-phenyl-3,4-dihydro-1′H,2H-[3,4′-bipyrazole] C27H22ClN7O2, (IX) and (3RS)-2-acetyl-5-(4-azidophenyl)-3′-methyl-5′-(naphthalen-2-yloxy)-1′-phenyl-3,4-dihydro-1′H,2H-[3,4′-bipyrazole] C31H25N7O2, (X), has Z′ = 1, and each is fully ordered. The new compounds have all been fully characterized by analysis, namely IR spectroscopy, 1H and 13C NMR spectroscopy, and mass spectrometry. In each of (II), (V) and (IX), the molecules are linked into ribbons, generated respectively by combinations of C—H...N, C—H...π and C—Cl...π interactions in (II), C—H...O and C—H...π hydrogen bonds in (V), and C—H...N and C—H...O hydrogen bonds in (IX). The molecules of compounds (IV) and (IX) are both linked into sheets, by multiple C—H...O and C—H...π hydrogen bonds in (IV), and by two C—H...π hydrogen bonds in (IX). A single C—H...N hydrogen bond links the molecules of (X) into centrosymmetric dimers. Comparisons are made with the structures of some related compounds.

Synthesis of New 1,3,5-Triazine-Based 2-Pyrazolines as Potential Anticancer Agents

A new series of 1,3,5-triazine-containing 2-pyrazoline derivatives (8–11)a–g was synthesized by cyclocondensation reactions of [(4,6-bis((2-hydroxyethyl)amino)-1,3,5-triazin-2-yl)amine]chalcones 7a–g with hydrazine hydrate and derivatives. Chalcones 7a–g were obtained by Claisen-Schmidt condensation between aromatic aldehydes and triazinic derivative 5, which was synthesized in high yield by a microwave-assisted reaction. Seventeen of the synthesized compounds were selected and tested by the US National Cancer Institute (NCI) for their anticancer activity against 58 different human tumor cell lines. Compounds 7g and 10d,e,g showed important GI50 values ranging from 0.569 to 16.6 µM and LC50 values ranging from 5.15 to >100 µM.

Cyclocondensation reactions of an electron deactivated 2-aminophenyl tethered imidazole with mono/1,2-biselectrophiles: synthesis and DFT studies on the rationalisation of imidazo[1,2-a]quinoxaline versus benzo[f]imidazo[1,5-a][1,3,5]triazepine selectivity switches

Microwave-assisted cyclocondensation of title compounds afforded unreported imidazo[1,2-a] quinoxaline and benzo[f]imidazo[1,5-a][1,3,5]triazepines in high yields.