A Simple,Convenient One‐Pot Synthesis of Dithio‐Carbamide Derivatives of Heterocyclic 1,3‐Dicarbonyl Systems

A various new dithi‐ocarbamides were synthesized from heterocyclic six‐membered 1,3‐dicarbonyl systems, such as 4‐hydroxy‐2,5‐pyranopyridines, 4‐hydroxy‐2‐pyridones, 4‐Hydroxy‐2‐quinolones, 4‐hydroxy‐coumarins, and 4‐hydroxy‐1‐methyl‐2‐quinolones. The dicarbonyl compounds in the presence of anhydrous potassium carbonate in dimethyformamide react with tetraalkylthiuram disulfides to yield 3‐dialkylaminothiocarbonylthio derivatives through a simple, convenient one‐pot reaction. The structures were confirmed by using IR, NMR, and elemental analysis.     

An Improved Reduction Procedure in the Synthesis of Substituted Pyrrolidines via An Aminomercuration/Reduction Sequence of Primary Alkenylamines

Aminomercuration/reduction sequence of δ-alkenylamines is a typical route to substituted pyrrolidines. Backward reaction to the starting material is a major drawback which occurs during sodium borohydride reduction of the intermediate organomercurial. We describe here a new reduction procedure which prevents almost completely this backward reaction and leads to significant increases in the yields of pyrrolidines.     

Anionic polymerization of N,N‐dialkyl‐2‐methylenebut‐3‐enamide: Effect of alkyl substituents on polymerization behavior

Anionic polymerizations of three 1,3‐butadiene derivatives containing different N,N‐dialkyl amide functions, N,N‐diisopropylamide (DiPA), piperidineamide (PiA), and cis‐2,6‐dimethylpiperidineamide (DMPA) were performed under various conditions, and their polymerization behavior was compared with that of N,N‐diethylamide analogue (DEA), which was previously reported. When polymerization of DiPA was performed at ?78 °C with potassium counter ion, only trace amounts of oligomers were formed, whereas polymers with a narrow molecular weight distribution were obtained in moderate yield when DiPA was polymerized at 0 °C in the presence of LiCl. Decrease in molecular weight and broadening of molecular weight distribution were observed when polymerization was performed at a higher temperature of 20 °C, presumably because of the effect of ceiling temperature. In the case of DMPA, no polymer was formed at 0 °C and polymers with relatively broad molecular weight distributions (M_w/M_n = 1.2) were obtained at 20 °C. The polymerization rate of PiA was much faster than that of the other monomers, and poly(PiA) was obtained in high yield even at ?78 °C in 24 h. The microstructure of the resulting polymers were exclusively 1,4‐ for poly(DMPA), whereas 20–30% of the 1,2‐structure was contained in poly(DiPA) and poly(PiA). © 2010 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 48: 3714–3721, 2010     

Preparation and Properties of Polyallenes. II. Phase Transitions of Polyallene

Polyallenes prepared with the aid of organoaluminum-VOCl₃ catalysts appear to exist in three distinct phases: two crystalline phases (I and II) and an amorphous phase. Phase I shows two strong X-ray diffraction peaks at d = 5.62 Å and d = 4.04 Å; phase II has three strong peaks at d = 6.28 Å, d = 5.03 Å, and d = 4.21 Å. The band of the amorphous phase has its maximum at about d = 5.6 Å.     

A Convenient One-Step Synthesis of 2-Hydroxy-1,3,5-Benzenetricarbaldehyde

The hexamethylenetetramine/trifluoroacetic acid system was demonstrated to be capable of introducing three aldehyde groups into the phenol molecule. Facile, one-step procedures were developed for the preparation of hitherto difficult to synthesize 2-hydroxy-1,3,5-benzenetricarbaldehyde starting from either phenol or 4-hydroxybenzaldehyde. New pKa measurements showed 2-hydroxy-1,3,5-benzenetricarbaldehyde to be an acid stronger than previously reported.     

Synthesis of New Bis‐imidazole Derivatives

The reaction of aldimines with α‐(hydroxyimino) ketones of type 10 (1,2‐diketone monooximes) was used to prepare 2‐unsubstituted imidazole 3‐oxides 11 bearing an alkanol chain at N(1) (Scheme 2, Table 1). These products were transformed into the corresponding 2H‐imidazol‐2‐ones 13 and 2H‐imidazole‐2‐thiones 14 by treatment with Ac₂O and 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione, respectively (Scheme 3). The three‐component reaction of 10 , formaldehyde, and an alkane‐1,ω‐diamine 15 gave the bis[1H‐imidazole 3‐oxides] 16 (Scheme 4, Table 2). With Ac₂O, 2,2,4,4‐tetramethylcyclobutane‐1,3‐dithione or Raney‐Ni, the latter reacted to give the corresponding bis[2H‐imidazol‐2‐ones] 19 and 20 , bis[2H‐imidazol‐2‐thione] 21 , and bis[imidazole] 22 , respectively (Schemes 5 and 6). The structures of 11a and 16b were established by X‐ray crystallography.     

Synthesis,Reactions, Characterization and Biological Evaluation of 2,3′‐Bipyridine Derivatives (III)

1‐Pyridin‐3‐yl‐3‐(2‐thienyl of 2‐furyl)prop‐2‐en‐1‐ones 1a , 1b reacted with 2‐cyanoethanethioamide 2 to afford the corresponding 4‐(thiophen‐2‐yl or furan‐2‐yl)‐6‐sulfanyl‐2,3′‐bipyridine‐5‐carbonitriles 3a , 3b . The synthetic potentiality of compounds 3a , 3b were investigated in the present study via their reactions with several active halogen containing compounds 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 5 , 5a , 5b . Our aim here is the synthesis of 4‐(2‐thienyl or 2‐furyl)‐6‐pyridin‐3‐ylthieno[2,3‐b]pyridin‐3‐amines 6a , 6b , 6c , 6d , 6e , 6g , 6h , 6i , 6j , 6k , 6l , 6m , 6n ,via 6‐(alkyl‐thio)‐4‐(2‐thienyl or 2‐furyl)‐2,3′‐bipyridine‐5‐carbonitriles 5a , 5b , 5c , 5d , 5e , 5i , 5j , 5k , 5l , 5m . The structures of all newly synthesized heterocyclic compounds were elucidated by considering the data of IR, ¹H‐NMR, mass spectra, as well as that of elemental analyses. Anti‐cancer, anti‐Alzheimer, and anti‐COX‐2 activities were investigated for all the newly synthesized heterocyclic compounds.     

Theoretical study of methoxy group influence in the gas‐phase elimination kinetics of methoxyalkyl chlorides

The unimolecular gas‐phase elimination kinetics of 2‐methoxy‐1‐chloroethane, 3‐methoxy‐1‐chloropropane, and 4‐methoxyl‐1‐chloroburane has been studied by using density functional theory (DFT) methods to propose the most reasonable mechanisms of decomposition of the aforementioned compounds. Calculation results of 2‐methoxy‐1‐chloroethane and 3‐methoxy‐1‐chloropropane suggest dehydrochlorination through a concerted nonsynchronous four‐centered cyclic transition state (TS) to give the corresponding olefin. In the case of 4‐methoxyl‐1‐chloroburane, in addition to the 1,2‐elimination mechanism, the anchimeric assistance by the methoxy group, through a polar five‐centered cyclic TS, provides additional pathways to give 4‐methoxy‐butene, tetrahydrofuran and chloromethane. The bond polarization of the C? Cl, in the direction of C^δ+ ··· Cl^δ?, is the limiting step of these elimination reactions. The significant increase in rate together with the formation of a cyclic product tetrahydrofuran in the gas‐phase elimination of 4‐methoxyl‐1‐chloroburane is attributed to neighboring group participation of the oxygen of the methoxy group in the TS. The theoretical calculations show a good agreement with the reported experimental results. © 2011 Wiley Periodicals, Inc. Int J Quantum Chem, 2011     

Microwave Promoted and Improved Thermal Synthesis of Spiro[Indole‐Pyranobenzopyrans] and Spiro[Indole‐Pyranoimidazoles]

Spiro[indole‐pyranoimidazoles] ( 5 ) and spiro[indole‐pyranobenzopyrans] ( 6 ) are readily synthesized in one step in 86–92 and 91–97% yields by the Michael condensation of 3‐dicyanomethylene‐2H‐indol‐2‐ones ( 2 ) with 1‐phenyl‐2‐thiohydantoin ( 3 ) and 4‐hydroxy‐2H‐1‐benzopyran‐2‐one ( 4 ), respectively, without using any catalyst under different reaction conditions (conventional heating and microwave irradiation using (a) polar solvents (b) neutral alumina/silica gel as inorganic solid support in solvent free conditions). 2 was synthesized in situ by the Knoevenagel condensation of indole‐2,3‐dione ( 1 ) and malononitrile in the absence of any catalyst. 100% conversion was observed in most cases on TLC which also showed the formation of a single product. The comparison between the various methods is established.     

The Decomposition Reaction of 4‐Acetylsydnones Arylhydrazones

The acidic decomposition of 4‐acetylsydnones arylhydrazones 2 results in the formation of 4‐arylhydrazo‐1,2‐pyrazolin‐5‐ones 3 and 4‐arylamino‐1,2,3‐triazoles 4 , respectively. The reactions of 4‐acetylsydnones 1 with arylhydrazines 5 afford compounds 3 as the only products in the absence of solvent.     

Quantitation of oxcarbazepine and its metabolites in human plasma by micellar electrokinetic chromatography

A reliable micellar electrokinetic chromatographic method for the determination of oxcarbazepine and its two main metabolites, 10-hydroxycarbamazepine and 10,11-trans-dihydroxy-10,11-dihydroxycarbamazepine, in human plasma was developed. The separation and determination of the analytes was achieved using a system consisting of 60 mM SDS in phosphate buffer (30 mM, pH 8.0), to which 20% (v/v) methanol was added. Separation was carried out in an uncoated fused-silica capillary with a separation voltage of 25 kV and currents typically less than 40 microA. Spectrophotometric detection was at 205 nm. Isolation of oxcarbazepine and its metabolites from plasma was accomplished by a solid-phase extraction procedure. The mean extraction yield of the analytes from plasma was higher than 94%. The linear correlation coefficients were better than 0.994 for all analytes. The limit of detection was 0.05 microg/mL, the limit of quantitation 0.15 microg/mL. The repeatability for the spiked blank plasma samples was lower than 1.9% and the intermediate precision lower than 2.1%, both expressed as RSD%. The results obtained analysing real plasma samples from epileptic patients under therapy with Tolep were satisfactory in terms of precision, accuracy and detectability.     

Synthesis of 3‐Aryl‐2‐methoxyinden‐1‐one (Z)‐Phenylhydrazones via Hydrobromic Acid‐Mediated Cyclization of 2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehyde Phenylhydrazones

2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehydes 2 , obtained by successive treatment of 1‐(1‐aryl‐2‐methoxyethenyl)‐2‐bromobenzenes 1 with BuLi and 1‐formylpiperidine, were transformed to the corresponding phenylhydrazones 3 on treatment with PhNHNH₂. When these hydrazones were allowed to react with conc. HBr, cyclization, followed by dehydrogenation with air occurred, furnished 3‐aryl‐2‐methoxyinden‐1‐one (Z)‐phenylhydrazones 4 .     

Synthesis and cytotoxic activity of silacycloalkyl‐substituted heterocyclic aldehydes and their thiosemicarbazones

A series of 5‐[1‐methylsilacyclo‐pentyl/‐hexyl]‐2‐furfural, 5‐[1‐methylsilacyclo‐pentyl/‐hexyl]‐2‐thiophene carbaldehyde and 1,1‐bis(5‐formyl‐2‐furyl)silacyclo‐pentane/‐hexane and their thiosemicarbazones has been synthesized and subjected to antitumour assay. The effects of the substituents and the heterocycle were examined to establish structure–activity relationships. Thiosemicarbazones of 5‐(1‐methylsilacyclohexyl)furfural and 5‐(1‐methylsilacyclopentyl)furfural were very active (1.0–4.0 µg ml^?1) in vitro against human fibrosarcoma HT‐1080 and mouse hepatoma MG‐22A cells. At the same time, they were less toxic for normal fibroblasts 3T3. All compounds synthesized exhibited low or moderate toxicity (LD₅₀ 152–1904 mg kg^?1). Copyright © 2005 John Wiley & Sons, Ltd.     

The Study on Synthesis of Some New 1,2,3‐Triazolylurea and Carbonyl Amide Derivatives

The study on syntheses of some N‐substituted‐N′‐[5‐methyl‐1‐(4‐chlorophenyl)‐1,2,3‐triazol‐4‐yl]‐urea 6a‐e and N‐substituted‐[5‐methyl‐1‐(4‐chlorophenyl)‐1,2,3‐triazol‐4‐yl]carbonyl amide 6f‐l derivatives were reported in this paper. The yielded products 6a‐l were confirmed by elemental analyses, NMR, MS and IR spectra.     

Substituent effect of the ester moiety of epoxysuccinates on the polycondensation with diamine

Di‐2,2,2‐trichloroethyl cis‐epoxysuccinate, di‐2‐cyanoethyl cis‐epoxysuccinate, and di‐2‐methoxyethyl cis‐epoxysuccinate were synthesized, and the substituent effect of the epoxysuccinates on the polycondensation with diamine was studied. The order of reactivities of the epoxysuccinates with m‐xylylenediamine was as follows: di‐trichloroethyl ester ≫ di‐cyanoethyl ester > di‐methoxyethyl ester, such was also confirmed by the model reaction of the epoxysuccinate with benzylamine. ¹H NMR and IR spectroscopic study and ab initio calculation also well explained the reactivity order. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 504–508, 2000     

Synthesis of 4,6‐Dimethyldibenzothiophene and 1,2,3,4‐Tetrahydro‐4,6‐dimethyldibenzothiophene via Tilak Annulation

1,2,3,4‐Tetrahydro‐4,6‐dimethyldibenzothiophene was prepared by coupling 2‐bromo‐3‐methylcyclohexanone with 2‐methylbenzenethiol and annulating the product with the aid of polyphosphoric acid. A mixture of 1,2,3,4‐tetrahydro‐4,6‐dimethyldibenzothiophene and 4,6‐dimethyldibenzothiophene was prepared by coupling 2‐bromo‐3‐methylcyclohex‐2‐en‐1‐one with 2‐methylbenzenethiol and annulating the product with the aid of polyphosphoric acid. 2‐Bromo‐3‐methylcyclohexanone was synthesized by conjugate addition of Me₃Al to 2‐bromocyclohex‐2‐en‐1‐one with CuBr as catalyst and 2‐bromo‐3‐methylcyclohex‐2‐en‐1‐one by bromination? elimination of 3‐methylcyclohex‐2‐en‐1‐one. 1,2,3,4,4a,9b‐Hexahydro‐4,6‐dimethyldibenzothiophene was prepared by reduction of 1,2,3,4‐tetrahydro‐4,6‐dimethyldibenzothiophene with Zn and CF₃COOH.     

Metal Derivatives of Heterocyclic Thioamides: Synthesis and Crystal Structures of Copper Complexes with 1‐Methyl‐1,3‐imidazoline‐2‐thione and 1,3‐Imidazoline‐2‐thione

Reactions of copper(I) halides (Cl, Br, I) with 1‐methyl‐1, 3‐imidazoline‐2‐thione (mimzSH) in 1 : 2 molar ratio yielded sulfur‐bridged dinuclear [Cu₂X₂(μ‐S‐mimzSH)₂(η¹‐S‐mimzSH)₂] (X = I, 1 , Br, 2 ; Cl, 3 ) complexes. Copper(I) iodide with 1,3‐imidazoline‐2‐thione (imzSH₂) and Ph₃P in 1 : 1 : 1 molar ratio has also formed a sulfur‐bridged dinuclear [Cu₂I₂(μ‐S‐imzSH₂)₂(PPh₃)₂] ( 4 ) complex. The central Cu(μ‐S)₂Cu cores form parallelograms with unequal Cu–S bond distances {2.324(2), 2.454(3) Å} ( 1 ); {2.3118(6), 2.5098(6) Å} ( 2 ); {2.3075(4), 2.5218(4) Å} ( 3 ); {2.3711(8), 2.4473(8) Å} ( 4 ). The Cu···Cu separations, 2.759–2.877Å in complexes 1 – 3 are much shorter than 3.3446Å in complex 4 . The weak intermolecular interactions {H₂CH···S^# ( 2 ); CH···Cl^# ( 3 ); NH···I^# ( 4 )} between dimeric units in complexes 2 – 4 lead to the formation of linear 1D polymers.     

A Novel and Efficient One‐Pot Synthesis of 2‐Aminopyrimidinones and Their Self‐Assembly

A three‐component reaction of benzaldehyde derivatives, methyl cyanoacetate, and guanidinium carbonate affords 2‐amino‐4‐aryl‐1,6‐dihydro‐6‐oxopyrimidine‐5‐carbonitriles and the four‐component reaction of benzaldehyde derivatives, methyl cyanoacetate, and guanidinium hydrochloride in the presence of piperidine leads to piperidinium salts of pyrimidinones. X‐ray crystallography data confirm self‐assembly and H‐bonding in these compounds.     

Separation and quantitation of fructose-6-phosphate and fructose-1 ,6-diphosphate by LC-ESI-MS for the evaluation of fructose-1,6-biphosphatase activity

An LC-ESI-MS method was developed for the identification and quantification of fructose-1,6-biphosphate (F1,6BP) and fructose-6-phosphate (F6P), respectively the substrate and the product of the enzymatic reaction catalysed by fructose-1,6-bisphosphatase (F1,6BPase). F1,6BPase, expressed predominantly in liver and kidney, is one of the rate-limiting enzymes of hepatic gluconeogenesis and has become a target for the development of new drugs for type 2 diabetes. The two sugar phosphates were separated on a Phenomenex Luna NH2 column (150 mm x 2.0 mm id) using the following mobile phase: 5 mM triethylamine acetate buffer/ACN (80:20) v/v in a linear pH gradient (from pH = 9 to 10 in 15 min) at the flow rate of 0.3 mL/min. The detection was performed with an IT mass spectrometer in negative polarity (full scan 100-450 m/z) and in SIM mode on the generated anions at m/z = 339 (F1,6BP) and m/z = 259 (F6P). Under the optimised final conditions, the method was validated for accuracy, specificity, precision (inter- and intradays RSD comprised between 1.0 and 6.3% over the range of concentrations used), linearity (50-400 microM), LODs (0.44 microM) and LOQs (1.47 microM), and the method was applied to F6P determination in the F1,6BPase catalysed hydrolysis of F1,6BP.     

Synthesis,Spectroscopy, and Structures of Mono‐ and Dinuclear Copper(I) Halide Complexes with 1,3‐Imidazolidine‐2‐thiones

Copper(I) halides with triphenyl phosphine and imidaozlidine‐2‐thiones (L ‐NMe, L ‐NEt, and L ‐NPh) in acetonitrile/methanol (or dichloromethane) yielded copper(I) mixed‐ligand complexes: mononuclear, namely, [CuCl(κ¹‐S‐L ‐NMe)(PPh₃)₂] ( 1 ), [CuBr(κ¹‐S‐L ‐NMe)(PPh₃)₂] ( 2 ), [CuBr(κ¹‐S‐L ‐NEt)(PPh₃)₂] ( 5 ), [CuI(κ¹‐S‐L ‐NEt)(PPh₃)₂] ( 6 ), [CuCl(κ¹‐S‐L ‐NPh)(PPh₃)₂] ( 7 ), and [CuBr(κ¹‐S‐L ‐NPh)(PPh₃)₂] ( 8 ), and dinuclear, [Cu₂(κ¹‐I)₂(μ‐S‐L ‐NMe)₂(PPh₃)₂] ( 3 ) and [Cu₂(μ‐Cl)₂(κ¹‐S‐L ‐NEt)₂(PPh₃)₂] ( 4 ). All complexes were characterized with analytical data, IR and NMR spectroscopy, and X‐ray crystallography. Complexes 2 – 4 , 7 , and 8 each formed crystals in the triclinic system with P$\bar{1}$ space group, whereas complexes 1 , 5 , and 6 crystallized in the monoclinic crystal system with space groups P2₁/c, C2/c, and P2₁/n, respectively. Complex 2 has shown two independent molecules, [(CuBr(κ¹‐S‐L ‐NMe)(PPh₃)₂] and [CuBr(PPh₃)₂] in the unit cell. For X = Cl, the thio‐ligand bonded to metal as terminal in complex 4 , whereas for X = I it is sulfur‐bridged in complex 3 .