Three isomeric forms of hydroxyphenyl‐2‐oxazoline: 2‐(2‐hydroxyphenyl)‐2‐oxazoline, 2‐(3‐hydroxyphenyl)‐2‐oxazoline and 2‐(4‐hydroxyphenyl)‐2‐oxazoline

Crystal structures are reported for three isomeric compounds, namely 2‐(2‐hydroxy­phenyl)‐2‐oxazoline, (I), 2‐(3‐hydroxy­phenyl)‐2‐oxazoline, (II), and 2‐(4‐hydroxy­phenyl)‐2‐oxazoline, (III), all C₉H₉NO₂ [systematic names: 2‐(4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenol, (I), 3‐(4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenol, (II), and 4‐(4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenol, (III)]. In these compounds, the deviation from coplanarity of the oxazoline and benzene rings is dependent on the position of the hydroxy group on the benzene ring. The coplanar arrangement in (I) is stabilized by a strong intra­molecular O—H⋯N hydrogen bond. Surprisingly, the 2‐oxazoline ring in mol­ecule B of (II) adopts a ³T₄ (^C2T_C3) conformation, while the 2‐oxazoline ring in mol­ecule A, as well as that in (I) and (III), is nearly planar, as expected. Tetra­mers of mol­ecules of (II) are formed and they are bound together via weak C—H⋯N hydrogen bonds. In (III), strong inter­molecular O—H⋯N hydrogen bonds and weak intra­molecular C—H⋯O hydrogen bonds lead to the formation of an infinite chain of mol­ecules perpendicular to the b direction. This paper also reports a theoretical investigation of hydrogen bonds, based on density functional theory (DFT) employing periodic boundary conditions.     

Dihydrooxazolones and dihydroimidazolones derived from acylglycines: syntheses,molecular structures and supramolecular assembly

Syntheses and structures are described for some alkylidene‐substituted dihydrooxazolones and dihydroimidazoles derived from simple acylglycines. A second, triclinic, polymorph of 4‐benzylidene‐2‐(4‐methylphenyl)‐1,3‐oxazol‐5(4H)‐one, C₁₇H₁₃NO₂, (I), has been identified and the structure of 2‐methyl‐4‐[(thiophen‐2‐yl)methylidene]‐1,3‐oxazol‐5(4H)‐one, C₉H₇NO₂S, (II), has been rerefined taking into account the orientational disorder of the thienyl group in each of the two independent molecules. The reactions of phenylhydrazine with 2‐phenyl‐4‐[(thiophen‐2‐yl)methylidene]‐1,3‐oxazol‐5(4H)‐one or 2‐(4‐methylphenyl)‐4‐[(thiophen‐2‐yl)methylidene]‐1,3‐oxazol‐5(4H)‐one yield, respectively, 3‐anilino‐2‐phenyl‐5‐[(thiophen‐2‐yl)methylidene]‐3,5‐dihydro‐4H‐imidazol‐4‐one, C₁₀H₁₅N₃OS, (III), and 3‐anilino‐2‐(4‐methylphenyl)‐5‐[(thiophen‐2‐yl)methylidene]‐3,5‐dihydro‐4H‐imidazol‐4‐one, C₂₁H₁₇N₃OS, (IV), which both exhibit orientational disorder in their thienyl groups. The reactions of 2‐phenyl‐4‐[(thiophen‐2‐yl)methylidene]‐1,3‐oxazol‐5(4H)‐one with hydrazine hydrate or with water yield, respectively, N‐[3‐hydrazinyl‐3‐oxo‐1‐(thiophen‐2‐yl)prop‐1‐en‐2‐yl]benzamide and 2‐(benzoylamino)‐3‐(thiophen‐2‐yl)prop‐2‐enoic acid, which in turn react, respectively, with thiophene‐2‐carbaldehyde to form 2‐phenyl‐5‐[(thiophen‐2‐yl)methylidene]‐3‐{[(E)‐(thiophen‐2‐yl)methylidene]amino}‐3,5‐dihydro‐4H‐imidazol‐4‐one, C₁₉H₁₃N₃OS₂, (V), which exhibits orientational disorder in only one of its thienyl groups, and with methanol to give methyl (2Z)‐2‐(benzoylamino)‐3‐(thiophen‐2‐yl)prop‐2‐enoate, C₁₅H₁₃NO₃S, (VI). There are no direction‐specific intermolecular interactions in the crystal structure of the triclinic polymorph of (I), but the molecules of (II) are linked by two independent C—H...O hydrogen bonds to form C₂²(14) chains. Compounds (III) and (IV) both form centrosymmetric R₂²(10) dimers built from N—H...O hydrogen bonds, while compound (V) forms a centrosymmetric R₂²(10) dimer built from C—H...O hydrogen bonds. In the structure of compound (VI), a combination of N—H...O and C—H...π(arene) hydrogen bonds links the molecules into sheets. Comparisons are made with some similar compounds.     

Synthesis and evaluation of polyacrylamides derived from polycyclic pendant naphthalene,indole, and phenothiazine based chalcone moiety as potent antimicrobial agents

Polycyclic chalcone‐containing polyacrylamides, namely, poly ((N‐(4‐((E)‐3‐(naphthalen‐6‐yl)‐3‐oxoprop‐1‐enyl) phenyl) acrylamide), poly((N‐(4‐((E)‐3‐(1H‐indol‐3‐yl)‐3‐oxoprop‐1‐enyl) phenyl) acrylamide), and poly((N‐(4‐((E)‐3‐oxo‐3‐(10H‐phenothiazin‐8‐yl) prop‐1‐enyl) phenyl) acrylamide), were synthesized by Claisen–Schmidt condensation reaction, followed by ultrasonic irradiation reduction. The synthesized polymers were characterized by Fourier transform infrared spectroscopy, ¹H nuclear magnetic resonance, and ¹³C nuclear magnetic resonance spectroscopic technique. The newly synthesized polymers have been screened for antibacterial and antifungal activities by using resazurin reduction assay method, and the resulting polyacrylamides showed promising activity against various tested bacteria and fungi. Among the polymers, poly((N‐(4‐((E)‐3‐oxo‐3‐(10H‐phenothiazin‐8‐yl) prop‐1‐enyl) phenyl) acrylamide) and poly((N‐(4‐((E)‐3‐(1H‐indol‐3‐yl)‐3‐oxoprop‐1‐enyl) phenyl) acrylamide) exhibited better antifungal and antibacterial activities than poly ((N‐(4‐((E)‐3‐(naphthalen‐6‐yl)‐3‐oxoprop‐1‐enyl) phenyl) acrylamide), whereas all the polymers do not show any sign of antibacterial and antifungal activity against Streptococcus faecalis and Candida glabrata. Copyright © 2016 John Wiley & Sons, Ltd.     

A novel optically active diblock copolymer composed of poly(ethylene glycol) and poly[N‐{o‐(4‐phenyl‐4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenyl}maleimide]: Synthesis,micellization behavior,and chiroptical property

A series of optically active amphiphilic block copolymers were synthesizedby using potassium alkoxide of poly(ethylene glycol) monomethyl ether (MeOPEGO^?K⁺) to initiate the anionic polymerization of N‐{o‐(4‐phenyl‐4,5‐dihydro‐1,3‐oxazol‐2‐yl)phenyl}maleimide [(R)‐PhOPMI]. The PEG‐macroinitiators generated in situ in the reaction between MeOPEGOH and potassium naphthylide in tetrahydrofuran. The synthetic procedure may provide the PEG‐b‐PPhOPMI copolymers with well‐defined structure, as evidenced by gel permeation chromatography, ¹H NMR, FTIR, and elemental analysis. In particular, the preparation of block copolymers having a laevorotation or dextrorotation activity was accomplished by changing the feed composition. The micellization was examined for the amphiphilic block copolymers in aqueous milieu by fluorescence spectroscopy, dynamic light scattering, and circular dichroism. The results indicate that the copolymers could form regular spherical micelles with core‐shell structure when the hydrophilic component was long enough; in contrast, the copolymers containing shorter PEG segments formed aggregates in large dimension due to the considerable interaction between hydrophobic PPhOPMI components. Also, it was found that the aggregated structure of the polymeric micelles is strongly dependent on the medium nature and the polymer concentration. © 2007 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 1025–1033, 2008     

Synthesis of some new five membered heterocycles,a facile synthesis of oxazolidinones

The synthesis and structural properties of two kinds of thiosemicarbazide derivatives ( 2a‐c and 3a‐c ) and one kind of semicarbazide derivatives ( 4a, 4b ) have been described. These compounds were synthesized by treating 2‐(4‐amino‐3‐alkyl‐5‐oxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐1‐yl)acetohydrazides ( 1a‐c ) with benzyl isothiocyanate, 3‐florophenyl isothiocyanate and benzylisocyanate, respectively. The synthesis of 4‐amino‐3‐alkyl‐1‐[(4‐alkyl‐5‐mercapto(or 5‐oxo)‐4H‐1,2,4‐triazol‐3‐yl)methyl]‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones ( 5a‐c, 6a‐c and 7 ) have been performed from the reaction with sodium hydroxide. On the other hand, the acidic treatment of compounds 2b, 3b and 4b has afforded 4‐amino‐3‐(4‐chlorobenzyl)‐1‐[(5‐alkylamino‐1,3,4‐thidazol(or 1,3,4‐oxazol)‐2‐yl)methyl]‐4,5‐dihydro‐1H‐1,2,4‐triazol‐5‐ones ( 8, 9 and 10 ). The condensation of thiosemi(or semi)carbazide derivatives ( 2a‐c, 3c and 4b ) with 4‐chlorophenacylbromide have resulted in the formation of 2‐[4‐amino‐3‐alkyl‐5‐oxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐1‐yl]‐N′‐(3,4‐dialkyl‐1,3‐thiazol(or oxazol)‐2(3H)‐yliden]acetohydrazides ( 11a‐c, 12, 13 ), while their condensation with chloroacetic acid has produced 2‐[4‐amino‐3‐alkyl‐5‐oxo‐4,5‐dihydro‐1H‐1,2,4‐triazol‐1‐yl]‐N′‐[3‐(3‐alkyl)]‐4‐oxo‐1,3‐thiazolidin(or oxazolidin)‐2‐yliden}acetohydrazides ( 14, 15 and 16 ). The spectral data and elemental analyses have support the proposed structures.     

Synthesis of novel isoindolone‐based medium‐sized macromolecules and triazole containing heterocyclic compounds

A series of novel isoindolone‐based macromolecules of medium‐sized heterocyclic rings, such as 7,8‐dihydro‐6H‐benzo[4,5][1,6,3]dioxazonino[2,3‐a]isoindol‐14(9aH)‐one derivatives ( 5a‐l ), were synthesized and its frame work incorporating with a triazole moiety on phenol, ie, 2‐(4‐((1‐(2‐methoxyphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)isoindoline‐1,3‐dione ( 9a‐f ) and also a triazole moiety on carboxylic acid, ie, (1‐(2‐methoxyphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl 4‐(1,3‐dioxoisoindolin‐2‐yl)benzoate derivatives ( 13a‐e ) with various substitutions on aryl ring system have synthesized. All the synthesized compounds were characterized and confirmed with IR, ¹H NMR_, ¹³C NMR, and ESI mass spectral analysis.     

光学活性N-邻噁唑啉苯基甲基丙烯酰胺聚合物的合成及其手性光学性质

在三氟甲磺酸稀土盐(Ln(OTf)3,Ln=La,Nd,Sm,Y)的存在下,光学纯N-邻唑啉苯基甲基丙烯酰胺((S)-MeOPMAM)经自由基聚合反应得到相应的光学活性聚合物.考察了稀土盐种类、用量及溶剂性质等因素对聚合反应立体化学的影响.研究发现,以Y(OTf)3为调节剂、正丁醇为溶剂的体系能在一定程度上提高聚合反应的全同立体定向性.聚合物的手性光学性质明显依赖于立构规整度,随全同含量增大,聚合物的比旋光度和π-π*电子跃迁区域的Cotton效应强度呈下降趋势.利用1H-NMR技术研究了上述聚合物与1,1′-联-2-萘酚(BINOL)的对映选择性相互作用,结果表明,全同三元组含量较高的聚合物不仅使酚羟基质子峰向低场位移,而且导致信号分裂.     

Synthese und Reaktivität von 2‐Brom‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol Molekülstruktur von Bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐yl)

Synthesis and Reactivity of 2‐Bromo‐1,3‐diethyl‐2,3‐dihydro‐1 H ‐1,3,2‐benzodiazaborole Molecular Structure of Bis(1,3‐diethyl‐2,3‐dihydro‐1 H ‐1,3,2‐benzodiazaborol‐2‐yl The reaction of a slurry of calcium hydride in toluene with N,N′‐diethyl‐o‐phenylenediamine ( 1 ) and boron tribromide affords 2‐bromo‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol ( 2 ) as a colorless oil. Compound 2 is converted into 2‐cyano‐1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborole ( 3 ) by treatment with silver cyanide in acetonitrile. Reaction of 2 with an equimolar amount of methyllithium affords 1,3‐diethyl‐2‐methyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborole ( 4 ). 1,3,2‐Benzodiazaborole is smoothly reduced by a potassium‐sodium alloy to yield bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐yl] ( 7 ), which crystallizes from n‐pentane as colorless needles. Compound 7 is also obtained from the reaction of 2 and LiSnMe₃ instead of the expected 2‐trimethylstannyl‐1,3,2‐benzodiazaborole. N,N′‐Bis(1,3‐diethyl‐2,3‐dihydro‐1 H‐1,3,2‐benzodiazaborol‐2‐ yl)‐1,2‐diamino‐ethane ( 6 ) results from the reaction of 2 with Li(en)C≡CH as the only boron containing product. Compounds 2 – 4 , 6 and 7 are characterized by means of elemental analyses and spectroscopy (IR, ¹H‐, ¹¹B{¹H}‐, ¹³C{¹H}‐NMR, MS). The molecular structure of 7 was elucidated by X‐ray diffraction analysis.     

Synthesis,structure and in vitro cytotoxicity testing of some 1,3,4‐oxadiazoline derivatives from 2‐hydroxy‐5‐iodobenzoic acid

The syntheses of nine new 5‐iodosalicylic acid‐based 1,3,4‐oxadiazoline derivatives starting from methyl salicylate are described. These compounds are 2‐[4‐acetyl‐5‐methyl‐5‐(3‐nitrophenyl)‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6a ), 2‐[4‐acetyl‐5‐methyl‐5‐(4‐nitrophenyl)‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6b ), 2‐(4‐acetyl‐5‐methyl‐5‐phenyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl)‐4‐iodophenyl acetate, C₁₉H₁₇IN₂O₄ ( 6c ), 2‐[4‐acetyl‐5‐(4‐fluorophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate, C₁₉H₁₆FIN₂O₄ ( 6d ), 2‐[4‐acetyl‐5‐(4‐chlorophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate, C₁₉H₁₆ClIN₂O₄ ( 6e ), 2‐[4‐acetyl‐5‐(3‐bromophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6f ), 2‐[4‐acetyl‐5‐(4‐bromophenyl)‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6g ), 2‐[4‐acetyl‐5‐methyl‐5‐(4‐methylphenyl)‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6h ) and 2‐[5‐(4‐acetamidophenyl)‐4‐acetyl‐5‐methyl‐4,5‐dihydro‐1,3,4‐oxadiazol‐2‐yl]‐4‐iodophenyl acetate ( 6i ). The compounds were characterized by mass, ¹H NMR and ¹³C NMR spectroscopies. Single‐crystal X‐ray diffraction studies were also carried out for 6c , 6d and 6e . Compounds 6c and 6d are isomorphous, with the 1,3,4‐oxadiazoline ring having an envelope conformation, where the disubstituted C atom is the flap. The packing is determined by C—H…O, C—H…π and I…π interactions. For 6e , the 1,3,4‐oxadiazoline ring is almost planar. In the packing, Cl…π interactions are observed, while the I atom is not involved in short interactions. Compounds 6d , 6e , 6f and 6h show good inhibiting abilities on the human cancer cell lines KB and Hep‐G2, with IC₅₀ values of 0.9–4.5 µM.     

Stress degradation of edaravone: Separation,isolation and characterization of major degradation products

In the present study the International Conference on Harmonization‐prescribed stress degradation was carried out to study the degradation profile of edaravone. To establish a Quality by Design (QbD)‐assisted stability‐indicating assay, the reaction solutions in which different degradation products were formed were mixed. Plackett Burman and central composite design were used to screen and optimize experimental variables to resolve edaravone and its impurities with good peak symmetry using an RP C₁₈ column. The method was validated according to International Conference on Harmonization guidelines. Seven unknown and two known degradation products were identified and characterized by LC‐MS/MS. Two major degradation products formed under thermal degradation were isolated and characterized as 4‐(4,5‐dihydro‐3‐methyl‐5‐oxo‐1‐phenyl‐1H‐pyrazol‐4‐yl‐4‐(4,5‐dihydro‐5‐hydroxy‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐4‐yl)‐3‐methyl‐1‐phenyl‐1H‐pyrazol‐5(4H)‐one and 3‐hydroxy‐dihydro‐thiazolo[1‐(2‐methyl‐buta‐1,3dienyl)‐1‐phenylhydrazine]5‐one. The degradation pathways of degradants were proposed based on m/z values.     

Stereocontrol during the free‐radical polymerization of methacrylates with Lewis acids

The free‐radical polymerizations of methyl methacrylate (MMA), ethyl methacrylate, isopropyl methacrylate, and 2‐methoxyethyl methacrylate were carried out in the presence of various Lewis acids. The MMA polymerization in the presence of scandium trifluoromethanesulfonate [Sc(OTf)₃] in toluene or CHCl₃ produced a polymer with a higher isotacticity and heterotacticity than that produced in the absence of Sc(OTf)₃. Similar effects were observed during the polymerization of the other monomers. ScCl₃, Yb(OTf)₃, Er(OTf)₃, HfCl₄, HfBr₄, and In(OTf)₃ also increased the isotacticity and heterotacticity of the polymers. The effects of the Lewis acids were greater in a solvent with a lower polarity and were negligible in tetrahydrofuran and N,N‐dimethylformamide. Sc(OTf)₃ was also found to accelerate the polymerization of MMA. On the basis of an NMR analysis of a mixture of Sc(OTf)₃, MMA, and poly(methyl methacrylate), the monomer–Sc(OTf)₃ interaction seems to be involved in the stereochemical mechanism of the polymerization. © 2001 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 39: 1463–1471, 2001     

New domino‐reaction for the synthesis of N4‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines and 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine

The model morpholine‐1‐carbothioic acid (2‐phenyl‐3H‐quinazolin‐4‐ylidene) amide (1) reacts with phenacyl bromides to afford N⁴‐(5‐aryl‐1,3‐oxathiol‐2‐yliden)‐2‐phenylquinazolin‐4‐amines (4) or N⁴‐(4,5‐diphenyl‐1,3‐oxathiol‐2‐yliden)‐2‐phenyl‐4‐aminoquinazoline ( 5 ) by a thermodynamically controlled reversible reaction favoring the enolate intermediate, while the 4‐[4‐aryl‐5‐(2‐phenylquinazolin‐4‐yl)‐1,3‐thiazol‐2‐yl]morpholine ( 8 ) was produced by a kinetically controlled reaction favoring the C‐anion intermediate. ¹H nmr, ¹³C nmr, ir, mass spectroscopy and x‐ray identified compounds ( 4 ), ( 5 ) and ( 8 ).     

A structural study of 4‐aminoantipyrine and six of its Schiff base derivatives

Six derivatives of 4‐amino‐1,5‐dimethyl‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐3‐one (4‐aminoantipyrine), C₁₁H₁₃N₃O, (I), have been synthesized and structurally characterized to investigate the changes in the observed hydrogen‐bonding motifs compared to the original 4‐aminoantipyrine. The derivatives were synthesized from the reactions of 4‐aminoantipyrine with various aldehyde‐, ketone‐ and ester‐containing molecules, producing (Z)‐methyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₆H₁₉N₃O₃, (II), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]but‐2‐enoate, C₁₇H₂₁N₃O₃, (III), ethyl 2‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]cyclohex‐1‐enecarboxylate, C₂₀H₂₅N₃O₃, (IV), (Z)‐ethyl 3‐[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]‐3‐phenylacrylate, C₂₂H₂₃N₃O₃, (V), 2‐cyano‐N‐(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)acetamide, C₁₄H₁₄N₄O₂, (VI), and (E)‐methyl 4‐{[(1,5‐dimethyl‐3‐oxo‐2‐phenyl‐2,3‐dihydro‐1H‐pyrazol‐4‐yl)amino]methyl}benzoate, C₂₀H₁₉N₃O₃, (VII). The asymmetric units of all these compounds have one molecule on a general position. The hydrogen bonding in (I) forms chains of molecules via intermolecular N—H...O hydrogen bonds around a crystallographic sixfold screw axis. In contrast, the formation of enamines for all derived compounds except (VII) favours the formation of a six‐membered intramolecular N—H...O hydrogen‐bonded ring in (II)–(V) and an intermolecular N—H...O hydrogen bond in (VI), whereas there is an intramolecular C—H...O hydrogen bond in the structure of imine (VII). All the reported compounds, except for (II), feature π–π interactions, while C—H...π interactions are observed in (II), C—H...O interactions are observed in (I), (III), (V) and (VI), and a C—O...π interaction is observed in (II).     

Novel glycosylated carboranylquinazolines for boron neutron capture therapy of tumors: synthesis,characterization, and in vitro toxicity studies

The synthesis of a series of N‐glycosyl caboranylquinazolines is described. The condensation reaction of nitro‐acetylanthranilic acid with aminophenylcarborane gave 3‐[(o‐carboran‐1‐yl)phenyl]‐2‐methyl‐6‐nitroquinazolin‐4(3H)‐one 1 followed by reduction with Na₂S to the corresponding 6‐amino‐3‐[(o‐carboran‐1‐yl)phenyl]‐2‐methylquinazolin‐4(3H)‐one 2 . Reaction of compound 2 with D‐glucose or D‐ribose in methanol in the presence of a catalytic amount of acetic acid affords boronated N‐glycosylaminoquinazolines namely: 2‐methyl‐3‐[4‐(o‐carboran‐1‐yl)phenyl]‐6‐[N‐β‐D‐glucopyranosyl)]aminoquinazolin‐4(3H)‐one 3 or 2‐methyl‐3‐[4‐(o‐carboran‐1‐yl)phenyl]‐6‐[N‐β‐D‐ribofuranosyl)]aminoquinazolin‐4(3H)‐one 4 , respectively. Degradation of the o‐caborane cage of compounds 3 and 4 yielded highly water‐soluble compounds of sodium 2‐methyl‐3‐[4‐( nido ‐undecarborate‐1‐yl)phenyl]‐6‐[N‐β‐D‐glucopyranosyl]aminoquinazolin‐4(3H)‐one 5 and sodium 2‐methyl‐3‐[4‐( nido ‐undecarborate‐1‐yl)phenyl]‐6‐[N‐β‐D‐ribofuranosyl)]aminoquinazolin‐4(3H)‐one 6 , respectively. The structures were established on the basis of elemental analysis, NMR, IR and mass spectrometry. The in vitro toxicity test using B16 melanoma cells showed that N‐glycosyl of nido ‐undecaboranylquinazolines ( 5 and 6 ), with higher water solubility, is not toxic at boron concentration of 3000 µg boron ml⁻¹, whereas, N‐glycosyl of closo ‐carboranylquinazolines ( 3 and 4 ) has LD₅₀ > 200 µg boron ml⁻¹. The compounds described here may be considered as potential agents for BNCT. Copyright © 2008 John Wiley & Sons, Ltd.     

Synthesis,Pharmacological, and Biological Screening of Novel Derivatives of Benzodiazepines

A series of novel 4‐(substituted phenyl)‐2‐(thiophen‐2‐yl)‐2,3‐dihydro‐1H‐benzo[b][1,4]diazepine have been synthesized from 3‐(substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one. 3‐(Substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one was prepared by condensing 2‐acetyl thiophene with various aromatic aldehydes in the presence of 20% NaOH as base. Different 3‐(substituted phenyl)‐1‐(thiophen‐2‐yl)prop‐2‐en‐1‐one on cyclization with o‐phenylenediamine in the presence of NaOH as base resulted in 4‐(substituted phenyl)‐2‐(thiophen‐2‐yl)‐2,3‐dihydro‐1H‐benzo[b][1,4]diazepine derivatives. The structures of synthesized compounds are confirmed by IR, ¹H NMR, mass spectra, and elemental analysis. All the compounds have been screened for their antimicrobial, analgesic, and anti‐inflammatory activities.     

Iron‐catalyzed radical polymerization of acrylamides in the presence of Lewis acid for simultaneous control of molecular weight and tacticity

This work is directed to the stereospecific living radical polymerization of acrylamides such as N,N‐dimethylacrylamide and N‐isopropylacrylamide with an iron complex and a Lewis acid. DMAM was polymerized with [FeCp(CO)₂]₂ in conjunction with an alkyl iodide [(CH₃)₂C(CO₂Et)I] as an initiator in the presence of Y(OTf)₃ in toluene/methanol (1/1) at 60 °C to be converted almost quantitatively to the polymers with controlled molecular weights and high isotacticity (m > 80%), wherein the Fe‐complex generates radical species from a covalent C? I bond of the dormant species and the Lewis acid controls the stereochemistry of the polymerization via coordination with the amide groups of the polymer terminal and the monomer. A series of Lewis acids were also used for the iron(I)‐catalyzed DMAM polymerization, and Yb(OTf)₃ and Yb(NTf₂)₃ proved effective in giving isotactic polymers without deteriorating the molecular weight control similar to Y(OTf)₃. Furthermore, a slight enhancement of isospecificity was observed for the iron‐catalyzed system in comparison with the α,α‐Azobisisobutyronitrile‐initiated, when coupled with Y(OTf)₃. Stereoblock polymerization of DMAM via a one‐pot reaction was also achieved by just adding the Y(OTf)₃ methanol solution in the course of the polymerization to give atactic‐b‐isotactic poly(DMAM). A similar but slightly lower control in the molecular weight and tacticity was achieved in the polymerization of NIPAM with [FeCp(CO)₂]₂/Y(OTf)₃. © 2006 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 44: 2086–2098, 2006     

A convenient route to pyridones,pyrazolo[2,3‐a]pyrimidines and pyrazolo[5,1‐c]triazines incorporating antipyrine moiety

Condensation of 4‐aminoantipyrine with ethyl acetoacetate, ethyl benzoylacetate, and ethyl cyanoacetate furnished the corresponding ethyl 3‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)aminoacrylate and 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide derivatives. The aminoacrylates derivatives react with acetonitrile and sodium hydride to give 2‐amino‐6‐methyl‐1‐(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)‐4‐pyridone. Reaction of the cyanoacetamide derivative with dimethylformamide‐dimethylacetal (DMF‐DMA) afforded 2‐cyano‐N‐[1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐pyrazol‐4‐yl]‐2‐(N,N‐dimethylamino)methylene acetamide in high yield. Treatment of the latter with 5‐aminopyrazole derivatives afforded the corresponding pyrazolo[2,3‐a]pyrimidines. 2‐cyano‐N‐[(1,2‐dihydro‐1,5‐dimethyl‐2‐phenyl‐3‐oxo‐3H‐pyrazol‐4‐yl)]acetamide also reacts with heterocyclic diazonium salts to give the corresponding pyrazolo[5,1‐c]‐1,2,4‐triazine derivatives. © 2004 Wiley Periodicals, Inc. Heteroatom Chem 15:508–514, 2004; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.20046     

Functionalized 2‐Hydrazinobenzothiazole with Isatin and Some Carbohydrates under Conventional and Ultrasound Methods and Their Biological Activities

Several chemical reactions were carried out on 3‐(benzothiazol‐2‐yl‐hydrazono)‐1,3‐dihydro‐indol‐2‐one ( 2 ). 3‐(Benzothiazol‐2‐yl‐hydrazono)‐1‐alkyl‐1,3‐dihydro‐indol‐2‐one 3a , 3b , 3c have been achieved. Reaction of compound 2 with ethyl bromoacetate in the presence of K₂CO₃ resulted the uncyclized product 4 . Reaction of compound 2 with benzoyl chloride afforded dibenzoyl derivative 5 . Compound 2 was smoothly acetylated by acetic anhydride in pyridine to give diacetyl derivative 6b . Moreover, when compound 4 reacted with methyl hydrazine, it yielded dihydrazide derivative 7 , whereas the hydrazinolysis of this compound with hydrazine hydrate gave the monohydrazide derivative 8 . {N‐(Benzothiazol‐2‐yl‐N′‐(3‐oxo‐3,4‐dihydro‐2H‐1,2,4‐triaza‐fluoren‐9‐ylidene)hydrazino]‐acetic acid ethyl ester ( 9 ) was prepared by ring closure of compound 8 by the action of glacial acetic acid. In addition, the reaction of 2‐hydrazinobenzothiazole ( 1 ) with d ‐glucose and d ‐arabinose in the presence of acetic acid yielded the hydrazones 10a , 10b , respectively. Acetylation of compound 10b gave compound 11b . On the other hand, compound 13 was obtained by the reaction of compound 1 with gama‐d ‐galactolactone ( 12 ). Acetylation of compound 13 with acetic anhydride in pyridin gave the corresponding N¹‐acetyl‐N²‐(benzothiazolyl)‐2‐yl)‐2,3,4,5,6‐penta‐O‐acetyl‐d ‐galacto‐hydrazide ( 14 ). Better yields and shorter reaction times were achieved using ultrasound irradiation. The structural investigation of the new compounds is based on chemical and spectroscopic evidence. Some selected derivatives were studied for their antimicrobial and antiviral activities.     

Conjugated polymers based on dicarboxylic imide‐substituted isothianaphthene and their applications in solar cells

Four new polymers containing a benzo[c]thiophene‐N‐dodecyl‐4,5‐dicarboxylic imide (DIITN) unit including the homopolymer and three donor–acceptor copolymers were designed, synthesized, and characterized. For these copolymers, DIITN unit with low bandgap was selected as an electron acceptor, whereas 5,5′‐(2,7‐bisthiophen‐2‐yl)‐9‐(2‐decyltetradecyl)‐9H‐carbazole), 5,5′‐(3,3′‐di‐n‐octylsilylene‐2,2′‐bithiophene), and 5,5′‐(2,7‐bisthiophen‐2‐yl‐9,9‐bisoctyl‐9H‐fluoren‐7‐yl) were chosen as the electron donor units to tune the highest occupied molecular orbital/lowest unoccupied molecular orbital (HOMO/LUMO) levels of the copolymers for better light harvesting. These polymers exhibit extended absorption in the visible and near‐infrared range and are soluble in common organic solvents. The relative low lying HOMO of these polymers promises good air stability and high open‐circuit voltage (V_oc) for photovoltaic application. Bulk heterojunction solar cells were fabricated by blending the copolymers with [6,6]‐phenyl‐C61‐butyric acid methyl ester or [6,6]‐phenyl‐C71‐butyric acid methyl ester (PC71BM). The best power conversion efficiency of 1.6% was achieved under simulated sunlight AM 1.5G (100 mW/cm²) from solar cells containing 20 wt % of the fluorene copolymer poly[5,5′‐(2,7‐bisthiophen‐2‐yl‐9,9‐bisoctyl‐9H‐fluoren‐7‐yl)‐alt‐2,9‐(benzo[c]thiophene‐N‐dodecyl‐4,5‐dicarboxylic imide)] and 80 wt % of PC71BM with a high open‐circuit voltage (V_oc) of 0.84 V. © 2011 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2012     

A novel potent non‐nucleoside reverse transcriptase inhibitor acyl­thio­carbamate derivative with extensive intra­molecular π–π inter­actions

In the crystal structure of the novel acyl­thio­carbamate derivative O‐[2‐(1,3‐dioxo‐2,3‐dihydro‐1H‐isoindol‐2‐yl)­ethyl] N‐(4‐methyl­phenyl)‐N‐(3‐nitro­benzoyl)thio­carbamate, C₂₅H₁₉N₃O₆S, intra‐ and inter­molecular π–π inter­actions occur between the phthalimide and N‐benzoyl moieties. The partial atomic charges, calculated by ab initio methods, are consistent with the observed structure.