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.     

Bromination Products of 2‐Substituted 5,7‐Dimethoxy‐4‐Naphthols

Bromination in acetic acid is favored at C‐8 in 5,7‐dimethoxy‐4‐naphthol when the C‐2 substituent is methyl carboxylate, whereas C‐1 is favored when the C‐2 substituent is either acetoxymethylene or methyl.     

Über die Oxo‐cyclotetraphosphane (PBut)4O1–4

Contributions to the Chemistry of Phosphorus. 243 On the Oxocyclotetraphosphanes (PBu^t)₄O_1–4 Under suitable conditions, the reaction of tetra‐tert‐butylcyclotetraphosphane, (PBu^t)₄, with dry atmospheric oxygen gives rise to the corresponding monoxide (PBu^t)₄O ( 1 ) which has been isolated by column chromatography. The reaction with hydrogen peroxide furnishes a mixture of oxocyclotetraphosphanes (PBu^t)₄O_1–4 consisting of two constitutionally isomeric dioxides (PBu^t)₄O₂ ( 2 a , 2 b ), the trioxide (PBu^t)₄O₃ ( 3 ), and the tetraoxide (PBu^t)₄O₄ ( 4 ), in addition to 1 . According to the ³¹P NMR parameters the oxygen atoms are exclusively exocyclically bonded to the phosphorus four‐membered ring. Which of the P atoms are present as λ⁵‐phosphorus follows from the different low‐field shifts of the individual P nuclei compared with the starting compound. Accordingly, 1 is 1,2,3,4‐Tetra‐tert‐butyl‐1‐oxocyclotetraphosphane, 2 a and 2 b are 1,2,3,4‐Tetra‐tert‐butyl‐1,2‐dioxo‐ and ‐1,3‐dioxocyclotetraphosphane, respectively, 3 is 1,2,3,4‐Tetra‐tert‐butyl‐1,2,3‐trioxocyclotetraphosphane, and 4 is 1,2,3,4‐Tetra‐tert‐butyl‐1,2,3,4‐tetraoxocyclotetraphosphane. When the oxidation reaction proceeds a fission of the P₄ ring takes place.     

Bromination of 4‐Dichloromethyl‐4‐methylcyclohexa‐2,5‐dien‐1‐ones

Bromination of 4‐dichloromethyl‐4‐methylcyclohexa‐2,5‐dien‐1‐one and 4‐dichloromethyl‐3,4‐dimethylcyclohexa‐2,5‐dien‐1‐one has been studied. The reaction conditions required for the formation of mono‐, di‐, and tribrominated products have been optimized.     

Trans‐3,5‐dihydroperoxy‐3,5‐dimethyl‐1,2‐dioxalane/HBr System as New,Effective, Mild and Non‐toxic Reagent for Synthesis of 2‐Aryl‐1H‐benzothiazoles and 2‐Aryl‐1‐arylmethyl‐1H‐benzimidazoles

Ttrans‐3,5‐dihydroperoxy‐3,5‐dimethyl‐1,2‐dioxalane has been used as new, effective, solid, inexpensive and nontoxic oxidant for in situ generation of Br⁺ from HBr. This system has been applied as catalyst for synthesis of 2‐aryl‐1H‐benzothiazoles and 2‐aryl‐1‐arylmethyl‐1H‐benzimidazoles at room temperature in excellent yields and high purity.     

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 .     

Regioselective Diastereomeric Michael Adducts as Building Blocks in Heterocyclic Synthesis

The reaction of 4‐(4‐acetylamino/bromophenyl)‐4‐oxobut‐2‐enoic acids with carbon nucleophiles afforded Michael adducts depending on the type of nucleophilic reagents and medium (acidic or basic). The adducts 2 and 3 were used as key starting materials to synthesize some heterocyclic compounds, which include pyridazinone, furanone, 1,2‐oxazin‐5‐one, 1.2‐diazapine, pyrane, and hydroxyl pyridine derivatives. The Steric factor plays an important role in regioselectivity. The structure of newly synthesized compounds was elucidated by elemental analysis and spectroscopic data.     

A New Solution—phase Parallel Synthesis of 2—Alkyamino—3—aryl—5—phenylmethylene—3,5—dihydro—4H—imidazol—4—ones

Thirteen new 2-alkylaminoimidazolones(4) wre rapidly synthesized by a new solution-phase parallel synthetic method,which includes aza-Wittig reaction of iminophosphorane(1) with aromatic isocyanate to give carbodi-imide(2) and subsequent reaction of 2 with various aliphatic primary amine in a parallel fashion.The products were confirmed by ^1H NMR,MS,IR and X-ray crystallographic analysis.The unusual selectivity of the cyclization was probably due to the deometry of the guanidine intermediate.     

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.     

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.     

t-Butyl Hypochlorite: A Powerful Electrophilic Aromatic Ring Chlorinating Agent

t-Butyl hypochlorite is an excellent aromatic ring chlorinating agent, under mild conditions, without any catalyst, of acetanilide. High regioselectivity is observed, the product being, nearly exclusively, para-chloroacetanilide.     

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 .     

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.     

Synthesis of 4‐Arylisocoumarins (=4‐Aryl‐1H‐2‐benzopyran‐1‐ones) through Acidic Hydrolysis of (Z)‐2‐(1‐Aryl‐2‐methoxyethenyl)benzaldehydes,Followed by Oxidation

4‐Arylisocoumarins (=4‐aryl‐1H‐2‐benzopyran‐1‐ones) 6 were prepared from 2‐(1‐aryl‐2‐methoxyethenyl)‐1‐bromobenzenes 1 . Successive treatment of these bromo styrenes with BuLi and 1‐formylpiperidine gave a mixture of (E)‐ and (Z)‐2‐(1‐aryl‐2‐methoxyethenyl)benzaldehydes 2 . Hydrolysis of (Z)‐isomers with conc. HBr, followed by pyridinium chlorochromate (PCC) oxidation of the resulting 1H‐2‐benzopyran‐1‐ol derivatives 4 (and 5 ), afforded the desired products.     

Efficient Synthesis of 2‐Aminothiazole‐4‐phenyl‐5‐acetamides via the Open Chain Tautomers of γ‐Keto Amides

A simple and efficient method is described for the synthesis of new functionalized 2‐aminothiazoles, the 2‐aminothiazole‐4‐phenyl‐5‐acetamides 5, in 67–96% yields based on an application of the Hantzsch synthesis. The method involves the reaction of thiourea with 3‐benzoyl‐3‐bromo‐propionamides 4 prepared from the corresponding 3‐benzoylpropionamides 3. The tautomeric structure of the γ‐keto amides 3 and 6 is directly related to the present study, because 2‐aminothiazoles 5 are readily obtained from the corresponding open chain γ‐keto amides 3.     

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.     

Melamine Trisulfunic Acid: An Efficient and Recyclable Solid Acid Catalyst for the Synthesis of 4,4′‐(Arylmethylene)‐bis‐(1H‐pyrazol‐5‐ols)

Melamine trisulfunic acid is employed as a recyclable catalyst for the condensation reaction of aromatic aldehydes with 3‐methyl‐l‐phenyl‐2‐pyrazolin‐5‐one. This condensation reaction was performed in ethanol under refluxing conditions giving 4,4′‐(arylmethylene)‐bis‐(3‐methyl‐1‐phenyl‐1H‐pyrazol‐5‐ols) in 80‐96% yields.     

Chemoselectivity in the Reaction of 2‐Diazo‐3‐oxo‐3‐phenylpropanal with Aldehydes and Ketones

The chemoselectivity in the reaction of 2‐diazo‐3‐oxo‐3‐phenylpropanal ( 1 ) with aldehydes and ketones in the presence of Et₃N was investigated. The results indicate that 1 reacts with aromatic aldehydes with weak electron‐donating substituents and cyclic ketones under formation of 6‐phenyl‐4H‐1,3‐dioxin‐4‐one derivatives. However, it reacts with aromatic aldehydes with electron‐withdrawing substituents to yield 1,3‐diaryl‐3‐hydroxypropan‐1‐ones, accompanied by chalcone derivatives in some cases. It did not react with linear ketones, aliphatic aldehydes, and aromatic aldehydes with strong electron‐donating substituents. A mechanism for the formation of 1,3‐diaryl‐3‐hydroxypropan‐1‐ones and chalcone derivatives is proposed. We also tried to react 1 with other unsaturated compounds, including various olefins and nitriles, and cumulated unsaturated compounds, such as N,N′‐dialkylcarbodiimines, phenyl isocyanate, isothiocyanate, and CS₂. Only with N,N′‐dialkylcarbodiimines, the expected cycloaddition took place.     

Novel Method for the Synthesis of 6,12‐Dihydro‐2‐Methylindolo[2,3‐ b]Carbazol‐6‐Ones

A novel method for the synthesis of 6,12‐dihydro‐2‐methylindolo[2,3‐b]carbazol‐6‐ones was developed from 1‐oxo‐2,3,4,9‐tetrahydro‐1H‐carbazol‐1‐one through methyl 6‐methyl‐2‐(1‐oxo‐2,3,4,9‐tetrahydro‐1H‐carbazol‐2‐yl)oxoacetate in good yields. This method provides an alternative path for the synthesis of this product using 2‐hydroxy methylene‐2,3,4,9‐tetrahydro‐1H‐carbazol‐1‐one.     

Biotransformation and metabolic profile of caudatin‐2,6‐dideoxy‐3‐O‐methy‐β‐d‐cymaropyranoside with human intestinal microflora by liquid chromatography quadrupole time‐of‐flight mass spectrometry

In our previous studies, caudatin‐2,6‐dideoxy‐3‐O‐methy‐β‐d‐ cymaropyranoside (CDMC) was for the first time isolated from Cynanchum auriculatum Royle ex Wightand and was reported to possess a wide range of biological activities. However, the routes and metabolites of CDMC produced by intestinal bacteria are not well understood. In this study, ultra‐performance liquid chromatography/quadrupole time‐of‐flight mass spectrometry (UPLC‐Q‐TOF‐MS) technique combined with Metabolynx^TMsoftware was applied to analyze metabolites of CDMC by human intestinal bacteria. The incubated samples collected for 48 h in an anaerobic incubator and extracted with ethyl acetate were analyzed by UPLC‐Q‐TOF‐MS within 12 min. Eight metabolites were identified based on MS and MS/MS data. The results indicated that hydrolysis, hydrogenation, demethylation and hydroxylation were the major metabolic pathways of CDMC in vitro. Seven strains of bacteria including Bacillus sp. 46, Enterococcus sp. 30 and sp. 45, Escherichia sp. 49A, sp. 64, sp. 68 and sp. 75 were further identified using 16S rRNA gene sequencing owing to their relatively strong metabolic capacity toward CDMC. The present study provides important information about metabolic routes of CDMC and the roles of different intestinal bacteria in the metabolism of CDMC. Moreover, those metabolites might influence the biological effect of CDMC in vivo, which affects the clinical effects of this medicinal plant. Copyright © 2015 John Wiley & Sons, Ltd.