The scope of the Heck arylation of enol ethers with arenediazonium salts: a new approach to the synthesis of flavonoids

The scope of the Heck arylation of cyclic and acyclic enol ethers with arenediazonium salts was evaluated. Arylation of 2,3-dihydrofuran yielded 2-aryl-2,5-dihydrofurans as the major adducts (>99:1) except when using n-Bu₄NHSO₄ as additive or 4-NO₂PhN₂BF₄ as arenediazonium salt. 2,3-Dihydropyran provided mixtures of the three possible isomeric Heck adducts. Arylation of n-butylvinylether with arenediazonium bearing electron-donating groups resulted in substituted acetophenones as almost exclusive products in good overall yields. Substituted 4H-chromenes provided 2-aryl-2H-chromenes in moderate yield when applying the Pd(OAc)₂/2,6-di-t-butyl-4-methylpyridine catalytic system, which were applied in the synthesis of flavonoids.     

Darstellung,Eigenschaften und Kristallstruktur von [2-(1′-methyl-4-imidazolyl)phenyl-1-C,3′-N]acetylacetonatopalladium(II)

Synthesis, Properties, and Structure of [2-(1′-methyl-4-imidazolyl)phenyl-1-C,3′-N]-palladium(II) Acetylacetonate The reaction of Di-μ-chloro-bis[2-(1′-methyl-4-imidazolyl)phenyl-1-C,3′-N]palladium(II) with Thallium(I) acetylacetonate yields [2-(1′-methyl-4-imidazolyl)phenyl-1-C,3′-N]palladium(II) acetylacetonate. The complex crystallizes monoclinic in the space group P2₁/n with the lattice constants a = 1302.4(3), b = 836.0(2), c = 1341.3(3) pm, β = 93.69(3)°. Pd has a squareplanar coordination by two O atoms of acetylacetonate, the N atom of the imidazole ring, and the C atom of the phenyl group. I.r., n.m.r., and mass spectra are reported.     

Cycloacylation of N-phenyl-N′-R-thioureas with 3-aryl-2-propenoyl chlorides

Cycloalkylation of N-phenyl-N′-R-thiourea with 3-aryl-2-propenoyl chlorides in acetone gives as products 6-aryl-3-phenyl-2-(R-imino)-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-one and their hydrochlorides. The same reaction carried out in acetone in the presence of K₂CO₃ leads to the formation of 6-aryl-3-phenyl-2-(R-imino)-2,3,5,6-tetrahydro-4H-1,3-thiazin-4-ones, N-(3-aryl-2-propenoyl)-N-phenylthioureas, 3-aryl-2-propenoylanilides, and phenyl isothiocyanate.     

A convenient,rapid microwave assisted synthesis of some novel 3-[(4-chloro-3-methylphenoxy)methyl]-6-aryl-5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles using acidic alumina

A facile synthesis of 3-[(4-chloro-3-methylphenoxy)methyl]-6-aryl-5,6-dihydro-[1,2,4]triazolo[3,4-b][1,3,4]thiadiazoles 3a–n has been achieved by microwave promoted condensation of 3-mercapto-4-amino-5-[(4-chloro-3-methylphenoxy)methyl]-4H-1,2,4-triazole 1 with various aromatic aldehydes 2a–n in presence of catalytic amount of p-TsOH (para-toluenesulphonic acid). The structures of 3a–n are supported by IR and ¹H and ¹³C NMR spectral data.     

Synthesis of Halogenated 1,5-Diarylimidazoles and Their Inhibitory Effects on LPS-Induced PGE2 Production in RAW 264.7 Cells

A series of halogenated 1,5-diarylimidazole compounds were synthesized and their inhibitory effects on LPS-induced PGE₂ production in RAW 264.7 cells were evaluated. A wide variety of 2,4-, 4-, and 2-halogenated 5-aryl-1-(4-methylsulfonylphenyl)imidazoles were synthesized for SAR study via two different pathways. Overall, 4-halogenated 5-aryl-1-(4-methylsulfonylphenyl)imidazoles, regardless of the species of halogen, exhibited very strong inhibitory activities of PGE₂ production. Among them, 4-chloro-5-(4-methoxyphenyl)-1-(4-methylsulfonylphenyl)imidazole (3, IC₅₀ 3.3 nM ± 2.93), and 4-chloro-5-(4-chlorophenyl)-1-(4-methylsulfonylphenyl)imidazole (13, IC₅₀ 5.3 nM ± 0.23) showed the best results.     

Ketalizations of aryl ω-(2-imidazolyl)alkyl ketones by glycerol and 3-mercapto-1,2-propanediol. synthesis and characterization of cis- and trans-{2-aryl-2-[ω-(2-imidazolyl)alkyl](1,3-dioxolan-4-yl and 1,3-oxathiolan-5-yl)}methanols

Aryl 2-[(2-imidazolyl)ethyl or 3-(2-imidazolyl)propyl]ketones were ketalized by glycerol or 3-mercapto-1,2-propanediol in boiling benzene in the presence of 4-toluenesulfonic acid to provide the title compounds. The aryl substituents are 4-chloro-, 4-bromo-, 4-fluoro-, or 2,4-dichlorophenyl. While aryl (2-imidazolyl)methyl ketones condensed with glycerol to form cis- and trans-{2-aryl-2-[(2-imidazolyl)methyl]-4-(hydroxymethyl)}-1,3-dioxolanes, related condensations with 3-mercapto-1,2-propanediol, under similar, or even more stringent reaction conditions, produced no 1,3-oxathiolane analogs, with the starting ketones being recovered. Separation and structure determination of these racemic cis and trans isomeric products are described. The structure of these stereoisomers was established by means of ¹H and ¹³C nmr correlation and nOe experiments. Selective methylation of the N-unsubstituted 2-imidazolyl alcohols with one equivalent sodium hydride and methyl iodide provided the corresponding N-methyl alcohols in excellent yields. With excess benzoyl chloride, N-unsubstituted 2-imidazolyl alcohols were initially converted to O, N-dibenzoates from which the N-benzoyl group was easily cleaved by ammonium hydroxide in ethanol to provide benzoate esters.     

Reactions of 4-acyl-1-alkoxyaryl-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones with nucleophilic reagents

4-Acetyl-1-alkoxyaryl-5-aryl-3-hydroxy-2,5-dihydro-1H-pyrrol-2-ones reacted with amines to give 1-alkoxyaryl-5-aryl-4-(1-R-aminoethylidene)pyrrolidine-2,3-diones. Reactions of amines with 4-benzoyl-substituted analogs involve nucleophilic attack on the C³ atom in the heteroring to produce the corresponding 3-R-amino-1-alkoxyaryl-5-aryl-4-benzoyl-2,5-dihydro-1H-pyrrol-2-ones. Reactions of the title compounds with hydrazine hydrate, regardless on the substituent on C₄, afforded 4-aryl-3-methyl(phenyl)-5-[2(4)-methoxyphenyl]-4,6-dihydropyrrolo[3,4-c]pyrazol-6-ones.     

Synthesis,Structure, and Keto-Enol Tautomerism of 3-R<Superscript>1</Superscript>-5,5-R<Superscript>2</Superscript>,R<Superscript>2</Superscript>-6-R<Superscript>3</Superscript>-2,3,5,6-Tetrahydropyran-2,4-diones

Ethyl esters of 2,4-dibromo-2-R¹-4-R²-3-oxopentanoic and -hexanoic acids react with zinc and aliphatic or aromatic aldehydes under the conditions of the Reformatskii reaction to give 3-R¹-5,5-R², R²-6-R³-2,3,5,6-tetrahydropyran-2,4-diones, which are obtained in three forms: keto, enol with enolization of the keto group, and enol with enolization of the ester group. The keto form is isolated by crystallization from a mixture of CCl₄ and petroleum ether; the first enol form, from MeOH, EtOH, and polar aprotic solvents; and the second enol form, from CHCl₃. The second enol form is oxidized in DMSO to form a keto compound containing a hydroxy group at the 3-position of the heteroring.     

M(HSO4)n-Promoted Synthesis of 2-Aryl-1-arylmethyl-1H-1,3-benzimidazole Derivatives

We have developed a highly selective synthesis of 2-aryl-1-arylmethyl-1H-1,3-benzimidazoles from the reaction of o-phenylenediamines and aromatic aldehydes in the presence of metal hydrogen sulfates [M(HSO₄)_n] in water and also under solvent-free conditions in good to excellent yields.     

Preparation of 1-aryl-2,2-difluoro enol esters via dehydrosulfonylation of α-(phenylsulfonyl)difluoromethylated benzoates

1-Aryl-2,2-difluoro enol benzoates 4 has been prepared from α-(phenylsulfonyl)-difluoromethylated benzoates 3, which can be readily obtained from the reactions between simple aldehydes and PhSO₂CF₂H (or TMSCF₂SO₂Ph). 2,2-Difluoro enol esters 4 are relatively more stable compounds than 2,2-difluoro enol sily ethers, and they promise to act as interesting fluorinated building blocks for further elaborations.     

Synthesis of 1H-pyrrolo[3,2-c]quinoline derivatives via palladium-catalyzed heteroannulation of 2-aryl-3-iodo-4-(phenylamino)quinolines and 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinolines

Palladium(0)/copper iodide catalyzed Sonogashira cross-coupling of 2-aryl-3-iodo-4-(phenylamino)quinolines with terminal alkynes afforded series of 1,2,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines in a single-step operation. Conversely, the 4-(N,N-allylphenylamino)-2-aryl-3-iodoquinoline derivatives were found to undergo PdCl₂(PPh₃)₂/CuI catalyzed intramolecular Heck reaction to yield the corresponding 1,3,4-trisubstituted 1H-pyrrolo[3,2-c]quinolines.     

Synthesis, structure, and antimicrobial activity of copper(II) chelates containing imidazole and condensation products of α-amino acids with salicylaldehyde and its derivatives

Salicylaldehyde, 5-bromo- and 5-nitrosalicylaldehydes, 2-hydroxynaphthalene-1-carbaldehyde, and 2,3-, 2,4-, and 2,5-dihydroxybenzaldehydes reacted with glycine, alanine, and phenylalanine in ethanol in the presence of imidazole (Im) and copper(II) acetate hydrate to give copper(II) chelates with the composition Cu(Im)(L) · nH₂O (H₂L is the condensation product of the above aldehydes with α-amino acids; n = 0–2). The structure of the complex Cu(Im)(L¹) [H₂L¹ = 2-(2-hydroxybenzylideneamino)acetic acid] was determined by X-ray analysis. The crystalline structure of [2-(2-hydroxybenzylideneamino)acetato](imidazole)copper is formed by polymeric chains of the Cu(Im)(L¹) molecules linked through bridging oxygen atoms in the carboxy groups of the Schiff base ligand. The coordination unit has a distorted tetragonal pyramid configuration, where the pyramid base is composed of the phenol and carboxy oxygen atoms, CH=N nitrogen atom in the ligand H₂L¹ and imidazole nitrogen atom. The oxygen atom in the carboxy group in the neighboring molecule occupies the apical position of the coordination pyramid. The other coordination compounds also have polynuclear structure with the Schiff base H₂L acting as doubly deprotonated tridentate O,N,O-ligand and bridging carboxy groups. Thermal decomposition of the complexes includes their dehydration (70–95°C), while complete thermal decomposition occurs at 360–530°C. The synthesized complexes showed selective antimicrobial activity in the concentration range from 75 to 300 μg/ml against a number of standard strains of Staphylococcus aureus and Escherichia coli.     

Reactions with 2-aminonicotinic acid,I Some 8-aza analogs of quinazolinones and derived tricyclic compounds

The fusion of 2-acetamidonicotinic acid witho-toluidine,p-bromoaniline oro-chloroaniline afforded the corresponding 3-aryl-2-methyl-pyrido-[2,3-d]pyrimidin-4(3H)-ones (4), the 8-aza analogs of 3-aryl-2-methyl-4-quinazolinones, alongside 2-aminonicotinic acid. 2-Methyl-3-2(2-methylphenyl)-pyrido[2,3-d]pyrimidin-4(3H)-one (4a), the 8-aza analog of methaqualone, was converted to the 2-substituted styryl derivatives6 by condensation with some aromatic aldehydes and to the tricyclic system, 10-aza-5,6-dihydro-3-hydroxy-5-(2-methylphenyl)-2-substituted-1H-pyrido [1,2-a] quinazoline-1,6-diones (8) by reaction with monosubstituted bis-2,4,6-trichlorophenyl malonates.     

Three-pillared layer metal–organic frameworks assembled by imidazole-4,5-dicarboxylate and rigid bisimidazole ligands: synthesis,crystal structure,and sensing nitroaromatics

Three-pillared layer metal–organic frameworks based on 1H-imidazole-4,5-dicarboxylate and linear bis(imidazole) ligands generally formulated as {[Co₃(idc)₂(bib)₃]·8H₂O}_n (1), {[Cd(Hidc)(bib)_0.5]}_n (2) and {[Cd(Hidc)(bibp)]}_n (3), where H₃idc = 1H-imidazole-4,5-dicarboxylate, bib = 1,4-bis(1-imidazolyl)benzene and bibp = 4,4′-bis(1-imidazolyl)biphenyl, have been solvothermally synthesized and structurally characterized by single-crystal X-ray diffraction. Compound 1 features a 3-D-pillared layer structure with 1-D channels, generated by honeycomb-like 2-D layer linked by bib ligands. Compound 2 consists of 2-D lumpy layers of [Cd₄(Hidc)₄], which are further connected by bridging ligands of bib to generate a pillared layer 3-D framework with 1-D channels. In 3, the 2-D corrugated honeycomb networks, structurally analogous to CFx, are pillared by bibp ligands to form a 3-D architecture with 1-D channels. Through selecting different metal ions and the length of pillared ligands, the pore sizes are adjusted in the three complexes. The potential of 2 and 3 for nitro explosive sensing is investigated through luminescence quenching experiments, which show that 3 can be applied as a fluorescent sensor for nitro compounds.     

The first application of 4-alkoxy-1,1,1-trifluoroalk-3-en-2-ones in a three-component condensation protocol for the synthesis of 3-acyl-4-aryl-2-(trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-ones

The one-pot, simple and efficient three-component condensation protocol for the preparation of a series of twenty-five new 3-acyl-4-aryl-2-(trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-ones, where aryl = Ph, 4-tolyl, 4-ClPh, 4-NO₂Ph and 4-CHOPh, and acyl = Ac, Bz, 4-FBz, furan-2-oyl, thien-2-oyl and naphth-1-oyl, employing 1,3-cyclohexanedione, five aryl aldehydes and for the first time, six 4-alkyl(aryl/heteroaryl)-4-methoxy-1,1,1-trifluoroalk-3-en-2-ones, is described. Yields in 15-75% were obtained when the MCRs were performed in the presence of a catalytic amount of triethylamine (25 mol%) and in ethanol as solvent under reflux for 16 h. A representative X-ray diffraction data for 3-acetyl-4-phenyl-2-(trifluoromethyl)-2-hydroxy-3,4,7,8-tetrahydro-2H-chromen-5(6H)-one is also showed.     

Simple one-pot multicomponent approach to polyfunctionalized 2-amino-1-methyl-6-(methylthio)-5-nitro-4-aryl-1,4-dihydropyridine-3-carbonitriles

A series of polyfunctionalized 2-amino-1-methyl-6-(methylthio)-5-nitro-4-aryl-1,4-dihydropyridine-3-carbonitriles have been prepared using a multicomponent condensation reaction between aromatic aldehydes, malononitrile, and (Z) N-methyl-1-(methylthio)-2-nitroethenamine in the presence of Et₃N in acetonitrile.     

Preparation of 3-Aryl-4-(5-ARYL-Δ2-1,2,4-Oxadiazolin-3-YL)Sydnones and their Conversion into 3-ARYL-4-(5-ARYL-1,2,4-Oxadiazol-3-YL)Sydnones

3-Aryl-4-(5-aryl-Δ²-1,2,4-oxadiazolin-3-yl)sydnones (5) were synthesized in high yields by the reaction of 3-arylsydnone-4-carboxamide oximes (prepared from the corresponding 3-arylsydnone-4-carbonitriles) with aromatic aldehydes in the presence of acid catalysts. No reaction occurred when aliphatic aldehydes were used. The oxadiazolin-3-ylsydnones (5) were easily converted into the corresponding 3-aryl-4-(5-aryl-1,2,4-oxadiazol-3-yl)sydnones by N-bromosuccinimide oxidation. The 3-arylsydnone-4-carbonitrile oxides were synthesized in good yields by N-bromosuccinimide oxidation of the corresponding 3-arylsydnone-4-carboxaldehyde oximes.     

Synthesis and cyclo-oligomerization of 2-(bromomethyl)-3-aryl-2-propenoic acid derivatives

2-Bromomethyl-3-aryl-2-propenoic acids have been synthesized from Baylis-Hillman adducts derived from aromatic aldehydes and t-butyl acrylates as new precursors in MBH chemistry. Further triolides were synthesized by the cyclo-oligomerization of 2-bromomethyl-3-aryl-2-propenoic acids in the presence of Cs₂CO₃ demonstrating the synthetic utility of these motifs.     

Synthesis of 1-(1-aryl-1H-1,2,3-triazol-4-yl)-β-carboline derivatives

Reaction of 5-methyl-1-aryl-1H-1,2,3-triazole-4-carbocylic acid chlorides with tryptamine derivatives afforded substituted 1-aryl-N-[2-(1H-indol-3-yl)ethyl]-5-methyl-1H-1,2,3-triazole-4-carboxamides. At heating these compounds in toluene in the presence of POCl₃ and P₂O₅ Bischler-Napieralski cyclization occurs giving 1-(1-aryl-5-methyl-1H-1,2,3-triazol-4-yl)-4,9-dihydro-3H-β-carbolines that can be transformed into β-carboline and tetrahydro-β-carboline derivatives.     

A direct arylation-oxidation route to 3-arylisoindolinone inhibitors of MDM2-p53 interaction

A route to the MDM2-p53 inhibitor isoindolinone pharmacophore from a pre-formed phthalimide is detailed. The route involves treatment of 3-hydroxy-2-(n-propyl)isoindolinone with a substituted benzene in the presence of triflic acid. The resulting 3-aryl-2-(n-propyl)isoindolinones are then oxidized to the corresponding 3-hydroxy-3-aryl-2-(n-propyl) isoindolinones by treatment with 2,2’-bipyridinium chlorochromate. The benzylic oxidation represents a rather rare oxochromium (VI)-mediated reaction in which a selective C-H to C-OH transformation occurs.