Synthesis of 1-(2-polyfluoroacylaminophenyl)-3-polyfluoroalkylpropane-1,3-diones and 2-polyfluoroalkyl-4-quinolones

The condensation of 2-aminoacetophenone with R^FCO₂Et (R^F = CF₃, CF₂H, CF₂CF₂H) in the presence of LiH in THF or Bu^tOK in Bu^tOH affords either 2-polyfluoroalkyl-4-quinolones or 1-(2-polyfluoroacylaminophenyl)-3-polyfluoroalkylpropane-1,3-diones, depending on the ratio of the initial reactants. The latter are hydrolyzed in an acidic medium to produce 2-polyfluoroalkyl-4-quinolones. N-Methyl-2-trifluoromethyl-4-quinolone was synthesized from 2-aminoacetophenone, CF₃CO₂Et, and MeI in the presence of Bu^tOK.     

Synthesis of amidine complexes by metal-mediated addition of amino acid esters to coordinated nitriles

The reaction of the nitrile platinum(IV) complex trans-[PtCl₄(EtCN)₂] with amino acid esters H₂NC(R¹)(R²)CO₂Me (R¹ = R² = H, H-Me, Me-Me, H-Ph) and H₂NCH₂CH₂CO₂Me in CH₂Cl₂ produces the amidine complexes trans-[PtCl₄{ Z-NH=C(Et)NHC(R¹)(R²)CO₂Me}₂] and trans-[PtCl₄{ Z-NH=C(Et)NHCH₂CH₂CO₂Me}₂], which were isolated in 70–80% yields and characterized by elemental analysis, mass spectrometry, IR spectroscopy, and ¹H and ¹³C{¹H} NMR spectroscopy. The structures of the complexes with R¹ = R² = H (1), R¹ = H, R² = Me (2), and R¹ = H, R² = Ph (4) were established by X-ray diffraction analysis.__________Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 3, pp. 601–605, March, 2005.     

Homogeneous and Solid-Gas Hydrogenation of Alkynes in the Presence of the Clusters Fe3(CO)9(ε-RC2 R 1) {R=R 1=Ph, Et; R=Me, R 1=Ph}: Characterization of New Metallacyclic Derivatives

The clusters Fe₃(CO)₉(RC₂ R ¹) (R=R ¹=Ph, Et; R=Me, R ¹=Ph), complexes 1a, 1b, 1c, containing an alkyne bound in perpendicular fashion with respect to a cluster edge, catalyze the hydrogenation of some acetylenes either under homogeneous and solid–gas conditions. We hypothesize that cluster catalysis occurs and that the catalytic activity is related to the coordinating ability of the alkynic substrates. Competition between hydrogenation and formation of metallacyclic byproducts occurs. The new metallacyclic derivatives Fe₃(CO)₆(-CO)₂{(RC₂ R ¹)(R ²C₂ R ³)}, Fe₂(CO)₆{(RC₂ R ¹)(R ²C₂ R ³)} {R=R ¹=Et, R ²=R ³=H, Ph; R ²=Me, R ³=Et, Ph; R ²=H, R ³=Bu ^t . R=R ¹=Ph, R ²=Me, R ³=Et, Ph} (complexes 2, 3) were found both in the homogeneous reaction mixtures and after the solid–gas reactions. The formation of these products lowers the catalytic activity.     

Simplified Approach to the Regiospecific Synthesis of Trichloromethylpyrazolines Using Microwave Irradiation

Twelve novel 3-alkyl[aryl]-1-carboxamides-5-trichloromethyl-5-hydroxy-4,5-dihydro-lH-pyrazole have been synthesized in good yields (72–90%) using environmentally benign microwave-induced techniques. The compounds were synthesized from the cyclocondensation of 4-alkoxy-1,1,1-trichloro-3-alkyl[aryl]-2-ones [Cl₃CC(O)C(R²) = C(R¹)OR, where R = Me, Et; R¹ = H, Me, Et, Pr, i-Pr, i-Bu, t-Bu, Ph, Ph-4-NO₂, Ph-4-F, Ph-4-Cl, Ph-4-Br; and R² = H, Me] with semicarbazide hydrochloride in the presence of pyridine and using methanol/water (3:1 v/v) as the solvent. The advantages of using microwave irradiation, rather than a conventional method, were demonstrated.     

Synthesis in Water and Antimicrobial Activity of 5-Trichloromethyl-4,5-dihydroisoxazoles

Two series of 5-trichloromethylisoxazoles were synthesized from the cyclocondensation of 1,1,1-trichloro-4-methoxy-3-alken-2-ones [Cl₃CC(O)C(R²) = C(R¹)OMe, where R¹ = H, Me, Et, Pr, iso-Pr, cyclo-Pr, Bu, terc-Bu, CH₂Br, CHBr₂, CH(Me)SMe, (CH₂)₂Ph, and Ph, and R² = H; R¹ = H and R² = Me and Et; R¹ and R² = -(CH₂)₄- and -(CH₂)₅-; and R¹ = Et and Ph and R² = Me] with hydroxylamine hydrochloride through a rapid one-pot reaction in water. The 5-trichloromethyl-4,5-dihydroisoxazoles were aromatized by reaction with concentrated sulfuric acid to obtain the respective 5-trichloromethylisoxazoles. Their structures were confirmed by elemental analysis, ¹H/¹³C nuclear magnetic resonance, and electron impact mass spectroscopy. Crystal structure analysis for 5-triclhoromethyl-5-hydroxy-3-propyl-4,5-dihydroisoxazole (2d) and 5-trichloromethyl-5-hydroxy-3,4-hexamethylene-4,5-dihydroisoxazole (2o) is presented. The antimicrobial activities of the 5-trichloromethyl-4,5-dihydroisoxazole derivatives were examined using the standard twofold dilution method against Gram-positive bacteria (Staphylococcus aureus), Gram-negative bacteria (Escherichia coli and Pseudomonas aeruginosa), and yeasts (Candida spp. and Cryptococcus neoformans). All of the tested 5-trichloromethyldihydroisoxazoles exhibited antibacterial and antifungal activities at the tested concentrations.

Supplemental materials are available for this article. Go to the publisher's online edition of Synthetic Communications® to view the free supplemental file.     

A Facile Synthesis of New L‐Proline‐Based Trifluoromethyl Oxazole Derivatives Using Microwave Irradiation and Conventional Method

Cyclization reaction of l ‐proline with trifluoroacetimidoyl chlorides has been developed as an efficient strategy for the synthesis of trifluoromethyl oxazole derivatives by two methods: (a) in the presence of K₂CO₃ as a base in acetonitrile at room temperature and (b) in the presence of K₂CO₃ as a base in acetonitrile using microwave irradiation, in one pot reaction. The microwave irradiation has been found to be the most efficient method. High yields and short reaction times were obtained for both electron‐releasing and electron‐withdrawing substituted N‐aryltrifluoroacetimidoyl chloride derivatives by microwave irradiation.     

Formation of substituted pyrazolines in the reaction of C,N-diphenylnitrilimine with a zwitterion derived from triisopropylphosphine and ethyl 2-cyanoacrylate

The reaction of C,N-diphenylnitrilimine with a P-zwitterion derived from Prⁱ ₃P and H₂C=C(CN)CO₂Et afforded the first representative of 2-pyrazolines containing the phosphonium group and products of the addition of nitrilimine to Prⁱ ₃P and H₂C=C(CN)CO₂Et. The reaction of the P-zwitterion with C-4-nitrophenyl-N-phenylnitrilimine gave rise to a condensation product of one Prⁱ ₃P molecule and two nitrilimine molecules. The three-dimensional structures of the compounds synthesized were established by X-ray diffraction analysis.     

The first synthesis of 8-aza-2-polyfluoroalkylchromones

The condensation of 3-acetyl-4,6-dimethyl-2-pyridone with R_FCO₂Et in the presence of LiH in dioxane affords corresponding R_F-containing β-diketones, whose dehydration under the action of conc. H₂SO₄ gives 8-aza-5,7-dimethyl-2-polyfluoroalkylchromones.     

Fixation of Metallo Nitrile Ylides and Metallo Nitrile Imines as Ligands in Transition Metal Complexes [1]

1,3‐Dipoles of the type metallo nitrile ylide and metallo nitrile imine were prepared by mono‐α‐deprotonation of CH‐acidic {[W(CO)₅CHCH₂PPh₃]PF₆, M(CO)₅CNCH₂CO₂R (M = Cr, W; R = Me, Et), [Pt(Cl)(CNCH₂CO₂Et)(PPh₃)₂]BF₄} and NH‐acidic isocyanide complexes (Cr(CO)₅CNNH₂) and were stabilized by coordination to a second transition metal complex fragment {Cr(CO)₅, [M(CO)₅]⁺ (M = Mn, Re), [FeCp(CO)₂]⁺, [Pt(Cl)(PR₃)₂]⁺ (R = Et, Ph)}. All dinuclear products 1 – 7 , 10 , and 11 are neutral species except [(Ph₃P)₂(Cl)Pt{μ₂‐CNCH(CO₂Et)}Pt(Cl)(PPh₃)₂]BF₄ ( 8 ). Complex (OC)₅W{μ₂‐CNCH(CO₂Et)}Pt(Cl)(PEt₃)₂ ( 5b ) was characterized by X‐ray diffraction. Twofold deprotonation/platination to give (OC)₅Cr{μ₃‐CNC(Ph)}[Pt(Cl)(PPh₃)₂]₂ ( 9 ) was achieved in the case of Cr(CO)₅CNCH₂Ph.     

Synthesis,Spectroscopic Studies,and Biological Activity of Organosilicon(iv) Complexes of Ligands Derived from 2-Aminobenzothiazole Derivatives and 2-Hydroxy-3-Methoxy Benzaldehyde

Abstract

The Schiff bases derived from the condensation of 2-aminobenzothiazole derivatives and 2-hydroxy-3-methoxybenzaldehyde and their silicon(IV) complexes with the general formula R₂Si(L)Cl (R = Et, Bu, Ph, L = 2-(2-hydroxy-3-methoxy) benzylideneaminobenzo-thiazole) have been synthesized. These complexes have been characterized by elemental analysis, molar conductance, and spectroscopic studies including IR and NMR (¹H, ¹³C, and ²⁹Si) spectroscopy. The analytical data suggest trigonal bipyramidal geometry around the silicon atom in the resulting complexes. The ligands and their organosilicon complexes have also been evaluated for in vitro antimicrobial activity against bacteria (Staphylococcus aureus, Bacillus subtilis, and Escherichia coli) and fungi (Aspergillus niger and Candida albicans). The complexes were found to be more potent as compared to the ligands.

Supplemental materials are available for this article. Go to the publisher's online edition of Phosphorus, Sulfur, and Silicon and the Related Elements to view the free supplemental file.     

Orienting Effect of the Cage Addends: The Case of Nucleophilic Cyclopropanation of C2‐C70(CF3)8

C₂‐C₇₀(CF₃)₈ was found to be a very promising substrate in the Bingel and the Bingel–Hirsch reactions combining perfect regioselectivity with much higher reactivity compared to its analogs. The reactions with diethyl malonate yield a single isomer of the monoadduct C₇₀(CF₃)₈[C(CO₂Et)₂] and a single C₂‐symmetrical bisadduct C₇₀(CF₃)₈[C(CO₂Et)₂]₂. The Bingel–Hirsch variation is particularly interesting in that it additionally affords, in a similar regioselective manner, the unexpected alkylated derivatives C₇₀(CF₃)₈[CH(CO₂Et)₂]H and C₇₀(CF₃)₈[C(CO₂Et)₂][CH(CO₂Et)₂]H. The novel compounds have been isolated and structurally characterized by means of ¹H and ¹⁹F NMR spectroscopy as well as single‐crystal X‐ray diffraction. The mechanistic and regiochemical aspects of the reaction are explained with the aid of DFT calculations.     

Synthesis of a deep-cavity thiacalix[4]arene

A novel thiacalix[4]arene derivative bearing four phenyl groups on the upper rim was prepared by the direct condensation of biphenyl-4-ol with elemental sulphur. As revealed by X-ray diffraction analysis, this compound adopts the cone conformation in the solid state, thus creating a cavity with an extended π-aromatic system potentially applicable for solid-state inclusion of suitable molecules. Subsequent alkylation (RI/K₂CO₃/acetone, R=Me, Et, Pr) yielded tetraalkylated derivatives, which were studied for their conformational preferences using ¹H NMR spectroscopy. While the Me or Et derivatives are conformationally mobile and exhibit thermodynamic equilibria of several conformers in solution (CDCl₃ or CD₂Cl₂), the corresponding propoxy derivative is infinitely stable at room temperature.     

Microwave assisted regiospecific synthesis of 5‐trifluoromethyl‐4,5‐dihydropyrazoles and—pyrazoles

The regiospecific synthesis of a series of twelve 5‐trifluoromethyl‐4,5‐dihydropyrazoles and ‐pyrazoles from the cyclocondesation reaction of 4‐alkoxy‐1,1,1‐trifluoro‐3‐alken‐2‐ones [F₃CC(O)CH=C(R¹)OR, where R¹ = Me, Et, Pr, iso‐Pr, Bu, iso‐Bu, Ph, H; and R = Me, Et] with phenylhydrazine in toluene by environmentally benign microwave induced techniques is reported. It is shown that under appropriated conditions, the variation of microwave irradiation power leads to 4,5‐dihydropyrazole or pyrazole derivatives. This paper also includes the use of montmorillonite K‐10 as a solid support for the synthesis of pyrazoles under solvent free conditions.     

A simple and highly efficient synthesis of N-phenyl-2-polyfluoroalkyl-4-quinolones from 2-anilinoacetophenone and RFCO2Et

The condensation of 2-anilinoacetophenone with R_FCO₂Et (R_F = CF₂H, CF₃, C₂F₅) in the presence of LiH in THF affords the corresponding N-phenyl-2-polyfluoroalkyl-4-quinolones in excellent yields.     

BIS(DITHIOSQUARAMIDE) LIGANDS AND THEIR COMPLEXES WITH DIVALENT NICKEL: THERMOCHROMIC BEHAVIOUR AND UNANTICIPATED FORMATION OF 2:2 SPECIES

Abstract

Reaction of two equivalents of N-mono- or di-substituted 3-amino-4-(n-butoxy)-3-cyclobutene-1,2-diones with a 1,2-diaminoethane gave N-mono- or di-substituted 1,2-bis((2-amino-1-cyclobutene-3,4-dione)amino)-ethane derivatives (bis(squaramides)). Reaction of the bis(squaramides) with excess P₄S₁₀ gave the analogous tetrathio derivatives (bis(dithiosquaramides), LH₂) of formula (NR¹R²)C₄S₂(NHCH₂CH₂NH)-C₄S₂(NR¹R²) (R¹=n-Bu, R²=H; R¹=R²=Et, n-Bu). The new bis(dithiosquaramide) ligands were characterized by elemental analysis, IR, ¹H NMR, ¹³C NMR, electronic, and mass spectroscopic methods. The complexes of these ligands with nickel(II) were prepared, isolated and characterized. The isolated complexes are neutral 2:2 species of formula Ni₂L₂, as evidenced by results from mass spectrometry, and they exhibit thermochromic behaviour in pyridine solution. Additional spectroscopic data (IR, NMR) are consistent with the ligands being coordinated only through sulfur donor atoms and a structure for the complexes is proposed.     

Synthesis and Crystal Structure of 7,8-Dihydroquinolino[2,3-a]acridine Derivatives

Novel 9-amino-3-substituted-1,2,3,4-acridin-1-one derivatives and 9,14-diamino-7-substituted-7,8-dihydroquinolino[2,3-a]acridine derivatives were synthesized by the condensation reaction of 5-substituted-1,3-cyclohexanedione with 2-aminobenzonitrile and substituted 2-aminobenzonitrile using p-toluenesulfonic acid, K₂CO₃, and Cu₂Cl₂ as catalysts. The structures of all compounds were characterized by elemental analysis, infrared, mass spectrometry, and ¹H and ¹³C NMR spectra. The crystal and molecular structures of 6, 14-diamino-3,4,11,12-tetramethoxy-7-phenyl-7,8-dihydroquinolino[2,3-a]acridine 5a have been determined by single-crystal x-ray diffraction analysis. The crystal of compound 5a belongs to triclinic with space group P-1, a = 1.06168(15) nm, b = 1.16951(17) nm, c = 1.6020(2) nm, α = 71.380(3)°, β = 77.686(3)°, γ = 66.743(3)°, Z = 2, V = 1.7231(4) nm³, R ₁ = 0.1060, and wR ₂ = 0.2192.     

Sterically-crowded pyrroles

The syntheses in good yields of a considerable number of moderately to severely sterically-crowded 1,2,5-trisubstituted pyrroles by means of modifications of the Knorr-Paal condensation are described. Notwithstanding reports to the contrary, the classical procedure; succeeded in moderately sterically-crowded cases, e.g., R² = R⁵ = Me, R¹ = i-Pr, Me₂CHMeCH-, Me₂N-, Ph₂N-, 9-carbazolo, subst. 4-morpholino, 1-piperazino, 1-piperidino, etc. A product-water azeotroping procedure succeeded in more severely sterically-crowded cases e.g., R² = R⁵ = Et, R¹ = i-Pr; R² = R⁵ = Me, R¹ = Me₃CCH₂-, R² = R⁵ = i-Pr, R¹ = PhCH₂-. Highly sterically-crowded pyrroles, e.g., R² = R⁵ = Me, R¹ = t-Bu, adamantyl, PhCH₂CMe₂; R² = R⁵ = Et, R¹ = t-Bu; R¹ = R² = R⁵ = i-Pr; R² = R⁵ = t-Ru, R¹ = Me, Et, PhCH₂-, were obtained using titanium tetrachloride as a Lewis acid catalyst and as a water scavenger. Infrared spectra of the reacting mixtures provided evidence pertinent to the mechanism of the reaction, which is discussed.     

Isolation and Characterization of intermediate in the Synthesis of α-Fluorodiesters

The anion [(EtO)₂P(O)CFCO₂Et]^?Li⁺, pregenerated from its precursor diethyl (carboethoxyfluoromethyl)phosphonate (EtO)₂P(O)CFHCO₂Et and n-butyllithium, was added via syringe to a THF solution of ethyl oxaiyl chloride to yield an acylated phosphonate (EtO)₂P(O)CF(COCO₂Et)CO₂Et. In situ reaction with Grignard reagents RMgX produces the α-fluorodiesters (E,Z)-R(CO₂Et)C=CFCO₂Et in good yields. In contrast, addition of ethyl oxalyl chloride to a THF solution of diethyl (carboethoxyfluoromethyl)phosphonate anion gives an isolated intermediate (EtO)₂P(O)CFCO₂Et(CO₂Et)C=CFCO₂Et. Subsequent reaction of this isolated intermediate with Grignard reagents also affords a one-pot synthesis of the α-fluorodiesters with high E-stereoselectivity. The E-stereoselectivity increases when HMPT or DMPU is used as a cosolvent in the preparation of diethyl 2-fluoro-3-phenylfumarate (E,Z)-Ph(CO₂Et)C=CFCO₂Et.     

Preparation of complexes formed in the reaction between diironnanocarbonyl and tetraalkyl(phenyl)diphosphine disulfides,R2P(S)P(S)R2 (R=Et,n -Pr,n -Bu,Ph)

Fe₂(CO)₉ and R₂P(S)P(S)R₂ (R = Et, n-Pr, n-Bu, Ph) react to form two types of cluster complexes Fe₃(CO)₉(μ₃-S)₂ (1), Fe₂(CO)₆(μ-SPR₂)₂ (2A)–(2D), [2A, R = Et; 2B, R = n-Pr; 2C, R = n-Bu; 2D, R = Ph]. The complexes result from phosphorus–phosphorus bond scission; in the former sulfur abstraction has also occurred. The complexes have been characterized by elemental analyses, FT-IR and ³¹P-[¹H]-NMR spectroscopy and mass spectrometry.     

Synthesis and antitumor evaluation of novel tetrahydrobenzo[4′,5′]thieno[3′,2′:5,6]pyrimido[1,2-b]isoquinoline derivatives

In the present study, a novel 8,9,10,11-tetrahydro-7H,14H-benzo[4′,5′] thieno[2′,3′:4,5]-1,3-oxazino[3,2-b]isoquinoline-7,14-dione 5 was prepared by condensation of 2-amino-3-carbethoxy-4,5,6,7-tetrahydrobenzothiophene with homophthalic anhydride under microwave irradiation, followed by alkaline hydrolysis and cyclization using acetyl chloride. Compound 5 was further allowed to react with different nitrogen nucleophiles to get new tetrahydrobenzothienopyrimido isoquinolinone derivatives. The structures of the prepared compounds were elucidated by IR, ¹H-NMR, ¹³C-NMR, and mass spectroscopy. The newly prepared compounds were tested in vitro against a panel of two human tumor cell lines, namely, hepatocellular carcinoma (liver) HepG2, and mammary gland breast MCF-7. Almost all the tested compounds showed satisfactory activity.