The structure and thermal properties of novel DOPO-containing 1,3-benzoxazines

Three DOPO (9,10-dihydro-9-oxa-10-phospha-phenanthrene-10-oxide)-containing benzoxazin (3a–3c) were successfully prepared from 2-hydroxybenzaldehyde, p-substituted aniline, and DOPO by a three-step procedure. Since the phosphorus and the adjacent aliphatic carbon are both chiral centers, two pairs of enantiomers exist in 3a, 3b, or 3c. Compound 3a′, which is a pair of enantiomers existing in 3a, was isolated using recrystallization in ethyl acetate solvent. All the structures were confirmed by FT-IR, NMR, and MS spectra. The X-ray analysis indicated that the 3a′ is the RR/SS enantiomers and belongs to the monoclinic crystal system, its space group being P2₁/c. The thermal properties were investigated by DSC and TG. It has been found that the peak temperature of thermally induced ring-opening reaction was around 260–270 °C. Compounds (3a–3c, 3a′, and 3c′) had two similar thermal processes from 50 to 600 °C in TG, whereas the compound 3b′ had three thermal processes. The char yields of 3a–3c were 18.10, 16.84, and 16.34 %, respectively, while those of 3a′–3c′ were 26.00, 31.80, and 19.21 %, respectively. The results indicated that compounds 3a′–3c′ had better char properties than 3a–3c.     

Synthesis and characterization of a series of chiral NHC–Pd complexes derived from l-phenylalanine

The synthesis of a series of chiral Pd(L)PyBr₂ (3a–3e) and Pd(L)PyCl₂ (4d and 4e) complexes from l-phenylalanine is presented (L = (S)-3-allyl-4-benzyl-1-(2,6-diisopropylphenyl)-imidazolin-2-ylidene (a), (S)-4-benzyl-1-(2,6-diisopropylphenyl)-3-(naphthalen-2-ylmethyl)imidazolin-2-ylidene (b), (S)-4-benzyl-3-(biphenyl-4-ylmethyl)-1-(2,6-diisopropylphenyl)imidazolin-2-ylidene (c), (S)-4-benzyl-1-(2,6-diisopropylphenyl)-3-(naphthalen-1-ylmethyl)imidazolin-2-ylidene (d) or (S)-4-benzyl-1-(2,6-diisopropylphenyl)-3-(2,4,6-trimethylbenzyl)imidazolin-2-ylidene (e). The complexes were characterized by physicochemical and spectroscopic methods, and the X-ray crystal structures of 3a–3c and 4d are reported. In each case, there is a slightly distorted square-planar geometry around palladium, which is surrounded by imidazolylidene, two trans halide ligands and a pyridine ligand. There are π–π stacking interactions in the crystal structures of these complexes. Complex 3a showed good catalytic activity in the Cu-free Sonogashira coupling reaction under aerobic conditions.     

Synthesis of 2,5-bis(piperidinomethyl)piperidine and 1,5-bis(aminomethyl)-3-azabicyclo[3.2.1]octanones

Schmidt reaction of mono- and bis-Mannich bases1 and2 c derived from cyclopentanone gave the corresponding basically substituted 2-piperidones3 and4, respectively. Reduction of the latter afforded5. DoubleMannich reaction of2 a–c with primary amines gave 3-azabicyclo[3.2.1]octanone derivatives6 a–e and7. The transamination of2 a was investigated.     

Synthesis of new water-soluble phosphonate calixazacrowns and their use as drug solubilizing agents

This study presents the selective chloromethylation of calix[4](aza)crown ethers 2a–c, using chloromethyl n-octyl ether and SnCl₄ in chloroform at room temperature in good yield for the first time. Chloromethylated products 2a–c are used as key intermediates to synthesize new water-soluble p-phosphonato calix[4](aza)crown ethers 5a–c. Liquid–liquid phase extraction and phase solubility studies with poor water soluble drug molecules such as nifedipine, niclosamide and furosemide are performed to evaluate their binding properties. Among the studied drugs, furosemide was the most effectively dissolved drug by p-phosphonato calix[4](aza)crown ethers 5a–c in water.     

Synthesis and in vitro cytotoxic evaluation of some novel hexahydroquinoline derivatives containing benzofuran moiety

A series of new ethyl 4-(2-(benzofuran-2-yl)-4-substituted-1,4,5,6,7,8-hexahydroquinolin-1-yl)-benzoate 3a–c was synthesized by Michael condensation of benzofuran chalcones 1a–c and cyclohexanone to give 2-(2-benzofuranyl)-4-substituted-5,6,7,8-tetrahydro-4-H -chromene 2a–c, followed by reaction of the latter with ethyl 4-aminobenzoate. Condensation of 3a–c with different amines afforded the corresponding amides 4a–e. On the other hand, upon treatment compounds 3a–c with hydrazine hydrate gave the benzohydrazide derivatives 5a–c. The reaction of compounds 5a–c with different thio/isocyanate gave the corresponding thiosemicarbazide and semicarbazide derivatives 6a–c. Meanwhile compounds 5a–c were reacted with ethyl cyanoacetate and different β-dicarbonyl compounds such as acetyl acetone, ethyl acetoacetate, and diethyl malonate to afford pyrazolyl derivatives 7a, b; 8a, b; 9a, b; and 10a–c, respectively. Moreover, 5a–c were reacted with carbon disulfide to synthesize the corresponding oxadiazolyl derivatives 11a–c, while their condensation with different aromatic aldehydes gave the corresponding Schiff bases 12a–d. Cytotoxic evaluation of some of the newly synthesized compounds against human hepatocellular carcinoma cell lines (HepG-2) revealed that the tested compounds produce promising inhibitory effect against the growth of HepG-2 cells with IC₅₀ values ranged from 11.9 to 19.3 µg/mL.     

Synthese von Pyridonen aus Enaminen und Cyanessigsäuren

Reaction of enamines1 a–e with cyanoacetic acids2 a,b in acetic anhydride at about 100°C yields the α-cyanoacetylated enamines3 a–g. Under the same conditions methyl 4-cyano-2-(2-pyridyl)-acetoacetate3 h is obtained from methyl 2-pyridylacetate and2 a. Compounds3 are cyclized in hydrochloric acid yielding the 4-hydroxy-2-pyridones4; on the other hand in ethanolic sodium ethoxide solution the 2-amino-4-pyridones are obtained. The esters5 a,b andd are saponified to give the acids7 a–c which decarboxylate at 250°C to8 a–c.     

In vitro antischistosomal evaluation of some newly synthesized praziquantel derivatives

Praziquantel, 2-(cyclohexylcarbonyl)-1,2,3,6,7,11b-hexahydro-4H-pyrazino[2,1-a]isoquinolin-4-one, was used as the parent starting material to synthesize a new series of praziquantel-3-arylidene derivatives 1a–c and praziquantel–Mannich bases 2a–d, hoping to obtain new antischistosomal compounds of more activity and lower adverse effects. The antischistosomal activity of the newly synthesized compounds was evaluated using in vitro Schistosoma mansoni worm killing tests. Both compounds 2c and 2d exhibited significant in vitro antischistosomal activity and may offer promising use as an antischistosomal drug either alone or in combination with praziquantel.     

Thermal studies of some biological active oxadiazoles

A series of new unsymmetrical 2,5-disubstituted 1,3,4-oxadiazoles (3a–d) has been synthesized to evaluate their antibacterial and thermal properties. All compounds have been tested for their in vitro antibacterial activity against two Gram-positive bacteria namely, Staphylococcus aureus and Bacillus subtilis. Among the tested compounds, compound 2-(4-chlorophenyl)-5-(thiophen-2-yl)-1,3,4-oxadiazole (3c) has been found to be most potent member having minimum inhibitory concentration. Thermal stability and melting point of compounds have been studied by TG and DSC analysis in air atmosphere at heating rate of 10 °C min^?1. Thermal degradation kinetics of the most potent antibacterial compound 3c has been carried out by multiple heating rate model free kinetic methods namely, Ozawa–Flynn–Wall, modified Coats-Redfern, and Kissinger.     

Synthesis and extraction abilities of mono-formylated calix[4]-1,3-aza-crown and its hydrazone derivatives

By formylation of calix[4]-1,3-aza-crown in hexamethylenetetramine/trifluoroacetic acid system, the first formylated calix[4]-aza-crown derivative 6 was synthesized in yield of 61%. Reacting compound 6 with salicyloyl hydrazine, 2,4-dinitrophenyl hydrazine, nicotinyl hydrazine or phenyl thiosemicarbazide afforded four novel calix[4]crown hydrazone derivatives 7a–d in yields of 70–90%. By condensating compound 6 with series of bifunctional reagents, the novel mono-bridged biscalix[4]-aza-crown hydrazone derivatives 8a–c were prepared in high yields. The extraction experiments showed that all new compounds were good receptors for metal cations, especially, for soft metal cations. The extraction results suggested that the hydrazone groups produced favorable influences for binding soft cations. The two calix[4]arene units in compounds 8a–c could bind metal cations concurrently.     

Über cyclische Guanidin—Mesityloxid- und Guanidin—Phoron-Kondensate

The basic product synthesized byTraube andSchwarz from mesityl oxide and guanidine has not been 4.4.6-trimethyl-4.5-dihydro-2-pyrimidinamine (1), but a mixture containing the 4.4.6-trimethyl-3.4-dihydro-2(1H)-pyrimidinimine (resp. an isomeric pyrimidinamine)2 a (resp.2 b, 2 c) and the dimeric 4.4′-methylenedi[2(1H)-pyrimidinimine] (resp. an isomeric methylenedipyrimidinamine)3 a (resp.3 b, 2 c) and the dimerisation reaction were studied in a series of experiments. The product of the reaction of guanidine and phorone is not the guanidinopropylpyrimidine8 ⁴, but the 4.4′-spirobi[2(1H)-pyrimidinimine] (resp. a spirobipyrimidinamine)11 a (resp.11 b, 11 c). No determination was possible on the basis of NMR whether the condensation products of guanidine—in solutions ofDMSO-d₆—are pyrimidinimines (2 a, 3 a, 11 a) or pyrimidinamines (2 b resp.2 c, 3 b resp.3 c, 11 b resp.11 c) or mixtures of the isomeric compounds. The NMR-and mass spectra of2 a (resp.2 b, 2 c),3 a (resp.3 b, 3 c),11 a (resp.11 b, 11 c) and their derivates are discussed.     

Five-, six- and eight-membered ring organosilicon chalcogenides of the types Z2(SiMe2)2E (Z = Me2Si, H2C; E = S, Se, Te), Z(SiMe2E)2MR2 (Z = Me2Si, H2C, O; E = S, Se, Te; M = Si, Ge, Sn, R = Me, Ph) and (SiMe2ZSiMe2E)2 (Z = Me2Si, H2C; E = S, Se)

Reactions of ClMe₂Si–Z–SiMe₂Cl (Z = SiMe₂ (1a), CH₂ (1c), O (1e)) with Li₂E (E = S, Se) yielded eight-membered ring compounds (SiMe₂ZSiMe₂E)₂ (3a–d) as well as acyclic oligomers (SiMe₂ZSiMe₂E)_x of different chain lengths. If 1:1 molar mixtures of 1a, 1c or 1e and a diorganodichlorosilane, -germane or -stannane (R₂MCl₂) are reacted with Li₂E (E = S, Se, Te), six-membered ring compounds Z(SiMe₂E)₂MR₂ (4a–7g) are formed exclusively. Five-membered rings Z₂(SiMe₂)₂E (Z = SiMe₂ (8a–c), CH₂ (9a–c); E = S, Se, Te) are obtained starting from the tetrasilane ClMe₂Si–(SiMe₂)₂–SiMe₂Cl (1b) or the disilylethane ClMe₂Si–(CH₂)₂–SiMe₂Cl (1d) by treatment with Li₂E. All products were characterized by multinuclear NMR spectroscopy (¹H, ¹³C, ²⁹Si, ¹¹⁹Sn, ⁷⁷Se, ¹²⁵Te, including coupling constants) and the effects of the different ring sizes towards NMR chemical shifts are discussed.     

Asymmetric synthesis of 3-substituted unsaturated prolines from chiral sulfoximine substituted allyl titanium(IV) complexes

An asymmetric synthesis of the 3-substituted Δ^3,4-unsaturated prolines 7a-e and 3-substituted 4-methylene prolines 14a-c starting from the corresponding γ,δ-unsaturated α-amino acids 4a-e and 11a-c, respectively, is described. Amino acid derivatives 4a-e and 11a-d were obtained through aminoalkylation of the corresponding sulfoximine substituted allyl titanium(IV) complexes 2a-e and 10a-d, respectively, with the N-tert-butylsulfonyl imino ester 3. Activation of sulfoximines 4a-e and 11a-c through methylation of the sulfoximine group followed by a KF mediated isomerization of the vinyl aminosulfoxonium salts 5a-e and 12a-c, respectively, to the corresponding allyl aminosulfoxonium salt 6a-e and 13a-c, respectively, and a subsequent intramolecular nucleophilic substitution of the allylic aminosulfoxonium group afforded the enantio- and diastereomerically pure proline derivatives in medium to high yields.     

Chinolizine und Indolizine,XIII. Acyl-2-hydroxy-4-chinolizinone

The reaction of 2-picolylketones (1 a, b) with reactive trichlorophenyl malonates (2 a–f) leads to 1-acyl-2-hydroxy-4-quinoliziones (3 a–i) which can be easily deacylated by boiling hydrochloric acid yielding 4-quinolizinones4 a–f. The 3-acetyl-2-hydroxy-4-quinolizinones6 and8 are obtained byKlosa-Ziegler acylation of4 a and7, respectively. The reaction of the acetyl compound3 a with acetic anhydride yields the 2-pyrone derivative9, whereas the propionyl derivative3 g yields the 4-pyrone10 under the same conditions. Nitration of3 e does not give the 1-nitro derivative12 but rather the 1,3-dinitro compound11.     

New fluorochromatouranylates of alkali metals: Synthesis and structure

Four new fluorochromatouranylates, namely, K[UO₂(CrO₄)F] · 1.5H₂O (I), Rb[UO₂(CrO₄)F] · 1.5H₂O (II), Rb[UO₂(CrO₄)F] · 0.5H₂O (III), and Cs[UO₂(CrO₄)F] · 0.5H₂O (IV), have been synthesized, and their crystallographic characteristics have been determined. All the compounds crystallize in monoclinic system, space group P2₁/c, with the unit cell parameters a = 13.1744(5) Å, b = 9.4598(3) Å, c = 13.0710(4) Å, β = 103.746(1)°, Z = 4, R = 0.0235 (I); a = 13.5902(7) Å, b = 9.5022(4) Å, c = 13.2271(6) Å, β = 102.914(2)°, Z = 4, R = 0.0247 (II); a = 24.7724(8) Å, b = 12.6671(4) Å, c = 9.4464(3) Å, β = 97.661(1)°, Z = 8, R = 0.0448 (III); a = 25.725(1) Å, b = 12.8261(5) Å, c = 9.4929(4) β = 97.208(1)°, Z = 8 (IV). The pairs of compounds I and II and compounds III and IV are isostructural. Crystals of compounds I–III have been subjected to complete X-ray diffraction study. It has been established that the structures of compounds I–III are built of [UO₂(CrO₄)F] _n ^n? layers, which are parallel to the (100) plane and linked into a framework by alkali-metal cations located between layers, together with water molecules. The effect of topological and geometric isomerism on the structural features of 34 known uranyl compounds of the AT³M² crystallochemical group, to which the studied compounds I–III also belong, is discussed.     

Synthesis and thermal behavior study of complexes of the type [Pd(μ-X)(4-eb-p-phen)]2 (X = Cl,Br, I,N3, NCO,SCN) and 4-eb-p-phen [bis(4-ethylbenzyl)p-phenylenediimine]

The Schiff base bis(4-ethylbenzyl) p-phenylenediimine, 4-eb-p-phen (1), and six new dimeric Pd(II) complexes of the type [Pd(μ-X)(4-eb-p-phen)]₂ {X = Cl (2), Br (3), I (4), N₃ (5), NCO (6), SCN (7)} have been synthesized and characterized by elemental analysis, IR spectroscopy, and ¹H and ¹³C{¹H}-NMR experiments. The thermal behavior of the complexes 2–7 has been investigated by means of thermogravimetry and differential thermal analysis. From the final decomposition temperatures, the thermal stability of the complexes can be ordered in the following sequence: 3 > 4 > 7 > 2 ≈ 5 > 6. The final products of the thermal decompositions were characterized as metallic palladium by X-ray powder diffraction (XRD).     

Synthesis and rearrangement of cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones: an access to cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones

2-Substituted-4a-hydroxy-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 2a-c were synthesized by an one-step cyclocondensation from the 5-substituted-2-amino-2-oxazolines 1a-c with ethyl 2-oxocyclohexanecarboxylate in ethanol at room temperature, and easily dehydrated to provide 2-substituted-9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-9-ones 3. In refluxing xylene, the reaction conducted with various ethyl 2-oxocycloalkanecarboxylates led to the two isomeric 2-substituted-8/9H-cycloalkyl[1,2-e]oxazolo[3,2-a]pyrimidin-8/9-ones 3 and 2-substituted-5H-cycloalkyl[1,2-d]oxazolo[3,2-a]pyrimidin-5-ones 4. The structure of some compounds was unambiguously established using X-ray crystallography. According to results from the DSC analysis of compound 2a, formation of the thermodynamically stable pyrimidinones 4 could be related to an intramolecular rearrangement of kinetically controlled pyrimidinones 3.     

Thermal decomposition of some silver(I) carboxylates under nitrogen atmosphere

The thermal decomposition reactions of CH₃CH₂C(CH₃)₂COOAg (1), (CH₃)₃SiCH₂COOAg (2), CF₃COOAg (3), (CH₃)₃CCOOAg (4), C₂H₅COOAg (5), C₃F₇COOAg (6), C₆F₁₃COOAg (7) and (CF₂)₃(COOAg)₂ (8) were studied in N₂ atmosphere using thermogravimetry (TG), derivative thermogravimetry and differential thermal analysis. Characterized compounds decomposed in one- or multi-step processes with metallic silver formation in the range 215–465 °C. TG-IR studies of gases evolved during thermolysis revealed products of decomposition, such as carboxylic acids, CO₂ and recombination reactions.     

Tribromogermyl monochelates — derivatives of N,N-disubstituted 2-hydroxycarboxylic amides

Reactions of GeBr₄ with N,N-dimethyl-2-trimethylsiloxypropionamide (2a), (S)-2-trime-thylsiloxypropionpyrrolidide ((S)-2b), and N,N-dimethyl-O-(trimethylsilyl)mandelamide (2c) afforded pentacoordinated neutral (O,O)-monochelates, viz., N,N-dimethyl-2-tribromoger-myloxypropionamide (3a), (S)-2-tribromogermyloxypropionpyrrolidide ((S)-3b), and N,N-dimethyl-O-(tribromogermyl)mandelamide (3c), respectively. X-ray diffraction study was performed for tribromides 3a, (S)-3b, and 3c, as well as for the N,N-dimethylmandelamide (1c) described earlier. According to the X-ray diffraction data, the Ge atom in tribromides 3a, (S)-3b, and 3c is pentacoordinated and has trigonal bipyramidal configuration with two halogen atoms and oxygen atom of the ether group in the equatorial positions and the halogen atom and the amide oxygen atom in the axial fragment, the bonds in which are somewhat longer as compared to the analogous bonds in tetracoordinated Ge compounds.     

Über die Reaktionen von 2-Cyclohexenonen mit Ammoniumthiocyanat bzw. Thioharnstoff Über Heterocyclen, 59. Mitteilung

The 2-cyclohexenones1 a, b andc react with NH₄SCN to give 3,5,5-trimethyl-, 3-methyl-5-phenyl- and 3-methyl-2-cyclohexeniminiumthiocyanates8 a, b andc resp. (i.e. salts of α,β-unsaturated imines) and not the expected diazabicyclononane-thiones5 a, b andc. Alternative formulae for the1—NH₄SCN-condensates are discussed and rejected on the basis of IR- and NMR-spectra and the chemical properties of5 a-c. By action of thiourea inMeOH/NaOMe the 2-cyclohexenones1a, d ande are transformed into 1-hydroxy-5,7,7-trimethyl-, 1-hydroxy-5-methyl- and 1-hydroxy-2,4-diazabicyclo[3.3.1]nonane-3-thiones5 a, d ande resp. The structure of the diazabicyclononane-thiones5 a, d ande is established by means of NMR-, IR- and MS-spectra. 8 a-c and5 e showed no significant herbicidal and only small fungicidal (8 b, c) and insecticidal (8 a-c) activities in screening tests.     

One-pot multicomponent synthesis of novel 1-thiazolyl-5-coumarin-3-yl-pyrazole derivatives and evaluation of their cytotoxic activity

A series of novel 1-thiazolyl-5-coumarin-3-yl-pyrazole derivatives (4a–l) were synthesized via one-pot multicomponent reaction of 5-substituted salicylaldehydes (1a–c), 4-hydroxy-6-methyl-2H-pyran-2-one (2) and 2-hydrazinyl-4-arylthiazoles (3a–d) in acetonitrile using a catalytic amount of piperidine under reflux conditions. This multicomponent approach has advantages such as reduced reaction time and a high product yield percentage when compared with corresponding multistep approaches. All the synthesized compounds were evaluated for their cytotoxic activity against Hep G2 (hepatocellular liver carcinoma) and MCF-7 (breast cancer) cell lines and compared with the standard drug Doxorubicin. Among all the compounds, compounds 4d against Hep G2, 4k against MCF-7 and 4e against both Hep G2 & MCF-7 showed excellent cytotoxic activity.