Heterocyclic Systems Containing Bridged Nitrogen Atom: Synthesis and Antibacterial Activity of 3‐(2‐Phenylquinolin‐4‐yl)/3‐(1‐p‐Chlorophenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐s‐triazolo[3,4‐b]‐1,3,4‐thiadiazine Derivatives

The condensation of 4‐amino‐5‐mercapto‐3‐(2‐phenylquinolin‐4‐yl)/3‐(1‐p‐chlorophenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazoles 1a‐b with chloroacetaldehyde 2a‐b , ω‐bromo‐ω‐(1H‐1,2,4‐triazol‐1‐yl)acetophenone 3a‐b , chloranil 4a‐b , 2‐bromocyclohexanone 5a‐b , 2,4′‐dibromoacetophenone 6a‐b and 2‐bromo‐6′‐methoxy‐2′‐acetonaphthone 7a‐b are described. The structures of the compounds synthesized were confirmed by elemental analyses, IR, 1H NMR and mass spectra. The antibacterial activities were also evaluated.     

Synthesis of optically active af‐(1‐Ethyl‐3‐methylhexahydro‐1,3‐diazin‐5‐yl)‐ and N‐(1‐Ethyl‐5‐methyloctahydro‐1,5‐diazocin‐3‐yl)pyridine‐3‐carboxamides

As part of the structure‐activity relationship of the dopamine D₂ and serotonin 5‐HT₃ receptors antagonist 1, which is a clinical candidate with a broad antiemetic activity, the synthesis and dopamine D₂ and serotonin 5‐HT₃ receptors binding affinity of (R)‐5‐bromo‐N‐(1‐ethyl‐3‐methylhexahydro‐1,3‐diazin‐5‐yl)‐ and (R)‐5‐bromo‐N‐(1‐ethyl‐5‐methyloctahydro‐1,5‐diazocin‐3‐yl)‐2‐methoxy‐6‐methylaminopyridine‐3‐carboxam‐ides ( 2 and 3 ) are described. Treatment of 1‐ethyl‐2‐(p‐toluenesulfonyl)amino‐3‐methylaminopropane dihy‐drochloride ( 4a ) with paraformaldehyde and successive deprotection gave the 5‐aminohexahydro‐1,3‐diazine 6 in excellent yield. 3‐Amino‐1‐ethyl‐5‐methyloctahydro‐1,5‐diazocine ( 15 ) was prepared from 2‐(benzyloxycarbonyl)amino‐3‐[[N‐(tert‐butoxycarbonyl)‐N‐methyl]amino]‐1‐ethylaminopropane ( 9 ) through the intramolecular amidation of (R)‐3‐[N‐[(2‐benzyloxycarbonylamino‐3‐methylamino)propyl]‐N‐ethyl]aminopropionic acid trifluoroacetate ( 12 ), followed by lithium aluminum hydride reduction of the resulting 6‐oxo‐1‐ethyl‐5‐methyloctahydrodiazocine ( 13 ) in 41% yield. Reaction of the amines 6 and 15 with 5‐bromo‐2‐methoxy‐6‐methylaminopyridine‐3‐carboxylic acid furnished the desired 2 and 3 , which showed much less potent affinity for dopamine D₂ receptors than 1 .     

An efficient synthesis of 5‐aryl‐4,5‐dihydro‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐1‐(4‐phenylthiazol‐2‐yl)pyrazoles

Some new target products 5‐aryl‐4,5‐dihydro‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐1‐(4‐phenylthiazol‐2‐yl)pyrazoles 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j have been synthesized by reaction of 2‐bromo‐1‐phenylethanone and compounds 4a , 4b , 4c , 4d , 4e , 4f , 4g , 4h , 4i , 4j which were prepared from the combination of thiosemicarbazide and (E)‐3‐aryl‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐prop‐2‐en‐1‐ones 3a , 3b , 3c , 3d , 3e , 3f , 3g , 3h , 3i , 3j . All the structures were established by MS, IR, CHN, and ¹H NMR spectra data. Synthesis of structure diversity is applied. J. Heterocyclic Chem., (2011).     

Novel Synthesis and Antimicrobial Activity of 3‐Substituted 5‐bromo‐7‐methyl‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazoles

4‐Methyl acetanilide ( 1 ) on treatment with bromine in acetic acid, followed by hydrolysis with dilute HCl/NaOH solution, yielded 2‐bromo‐4‐methyl aniline ( 2 ), which on treatment with sodium thiocyanate in acetic acid afforded 2‐amino‐4‐bromo‐6‐methyl benzothiazole ( 3 ). Compound 3 in ethylene glycol was heated at 150°C with 80% hydrazine hydrate to get 4‐bromo‐2‐hydrazino‐6‐methyl benzothiazole ( 4 ). This hydrazino compound 4 on heating with formic acid for 3 h yielded 4‐bromo‐2‐hydrazinoformyl‐6‐methyl benzothiazole ( 5 ). Same compound 4 when heated independently with formic acid for 6 h/urea for 3 h/carbon disulfide in alkali afforded 5‐bromo‐7‐methyl ( 6 )/5‐bromo‐3‐hydroxy‐7‐methyl ( 7 )/5‐bromo‐3‐mercapto‐7‐methyl ( 8 )‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazoles, respectively. Compound 4 on heating with acetic acid/acetic anhydride gave acetyl benzothiazolyl derivative 9 , which on cyclization with orthophosphoric acid yielded 5‐bromo‐3,7‐dimethyl‐1,2,4‐triazolo‐[3,4‐b]‐benzothiazole ( 10 ). All these newly synthesized compounds were screened for antimicrobial activity against Escherichia coli (Gram ?ve), Bacillus subtilis (Gram +ve), Erwinia carotovora, and Xanthomonas citri using ampicillin, streptomycin, and penicillin as a standard for comparison.     

Synthesis of Novel 3‐(3‐(5‐Methylisoxazol‐3‐yl)‐7H‐[1,2,4]Triazolo [3,4‐b][1,3,4]Thiadiazin‐6‐yl)‐2H‐Chromen‐2‐Ones

A novel series of coumarin substituted triazolo‐thiadiazine derivatives were designed and synthesized by using 5‐methyl isoxazole‐3‐carboxylic acid ( 1 ), thiocarbohydrazide ( 2 ), and various substituted 3‐(2‐bromo acetyl) coumarins ( 4a , 4b , 4c , 4e , 4d , 4f , 4g , 4h , 4i , 4j ). Fusion of 5‐methyl isoxazole‐3‐carboxylic acid with thiocarbohydrazide resulted in the formation of the intermediate 4‐amino‐5‐(5‐methylisoxazol‐3‐yl)‐4H‐1,2,4‐triazole‐3‐thiol ( 3 ). This intermediate on further reaction with substituted 3‐(2‐bromo acetyl) coumarins under simple reaction conditions formed the title products 3‐(3‐(5‐methylisoxazol‐3‐yl)‐7H‐[1,2,4]triazolo[3,4‐b][1,3,4]thiadiazin‐6‐yl‐2H‐chromen‐2‐ones ( 5a , 5b , 5c , 5d , 5e , 5f , 5g , 5h , 5i , 5j ) in good to excellent yields. All the synthesized compounds were well characterized by physical, analytical, and spectroscopic techniques.     

Synthesis,properties and X‐ray structure of 5‐azido‐2‐methoxy‐1,3‐xylyl‐18‐crown‐5

5‐Azido‐2‐methoxy‐1,3‐xylyl‐18‐crown‐5 has been prepared by reacting p‐toluenesulfonyl azide with the carbanion generated from the reaction of 5‐bromo‐2‐methoxy‐1,3‐xylyl‐18‐crown‐5 with n‐butyl lithium. The asymmetric N₃ stretch of this product has been observed as a single band at 2110 cm^?1 in dichloromethane solution. Addition of solid NaSCN, KSCN and CsSCN shifts this band to 2115, 2113 and 2112 cm^?1, respectively. Computational studies of this azide at the B3LYP‐6‐31G* level in the presence and absence of Na⁺ predicted these bands to be at 2173 cm^?1 and 2184 cm^?1. For the salt‐containing solutions, additional bands were observed at 2066 cm^?1, 2056 cm^?1 and 2055 cm^?1, respectively, which are in the range expected for CN stretches. The X‐ray structure of this azide has been determined. The terminal and internal N? N bond lengths were found to be 1.127(2) and 1.245(2) Δ, respectively, which is the usual pattern for aromatic azides. The crown ether is looped over the face of the aromatic ring resulting in an angle of 38.94° between the plane defined by the aromatic ring and that defined by the five ring oxygen atoms. In addition, the CH₃ group is rotated out of the plane of the phenyl ring with C1‐C18‐O181‐C182 and C17‐C18‐O181‐C182 dihedral angles of 93.81(14)° and ‐90.54(14)°, respectively.     

Design and Synthesis of Novel 6‐(5‐Methyl‐1H‐1,2,3‐triazol‐4‐yl)‐5‐[(2‐(thiazol‐2‐yl)hydrazono)methyl]imidazo[2,1‐b]thiazoles as Antimicrobial Agents

Novel 6‐(1,2,3‐triazol‐4‐yl)‐5‐[(2‐(thiazol‐2‐yl)hydrazono)methyl]imidazo[2,1‐b ]thiazoles 7 , 9a , 9b , 9c , 9d , and 11 were prepared by reaction of thiosemicarbazone 5a , 5b with either hydrazonoyl chloride 6 , phenacylbromides 8 or 2‐bromo‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)ethanone 10 respectively. The new products were tested for their antimicrobial activities using 96‐well micro‐plate assay, and compound 7 showed excellent antibacterial activities compared with Vancomycine (reference drugs), while compounds 5b and 9c exhibited good results against yeast. The minimum inhibitory concentration (MIC) was determined, and compound 7 showed the lowest MIC against Gram positive bacteria while compound 5b showed the lowest MIC against yeast.     

Synthesis of New tert‐Butyl‐ and Bromo‐functionalized [1,2,4]Triazino [5,6‐b]indole‐3‐thiols and Indolo[2,3‐b]quinoxalines

In the present investigation, the synthesis of a series of structurally new and interesting tert‐butyl‐ and bromo‐functionalized [1,2,4]triazino[5,6‐b ]indoles ( 6a – f ) and indolo[2,3‐b ]quinoxalines ( 8a – f ) has been achieved, involving the condensation reaction of 7‐bromo‐5‐tert‐butylisatins ( 4a – f ) with thiosemicarbazide ( 5 ) and benzene‐1,2‐diamine ( 7 ). The substrates 4a – f were prepared through bromination reaction of 5‐tert‐butylisatin ( 3 ) with NBS in PEG‐400 followed by alkylation reaction. The molecular structures of these newly synthesized compounds were elucidated on the basis of their elemental analyses and spectral data.     

Reaction of 6‐Methyl‐2‐Thiouracil and 6‐Phenyl‐2‐Thiouracil with Chloro‐β‐Dicarbonyl and Bromo‐β‐Dicarbonyl Compounds and Their Nitrile Analogs

Derivatives of 2‐methylidene‐1,3‐dihydropyrimidin‐4‐ones 2a , 2b , 2c , 2d , 2e , 2f , 2g were synthesized by interaction of 6‐methyl‐2‐thiouracil and 6‐phenyl‐2‐thiouracil 1a , 1b with some activated halogenides: diethyl bromomalonate, ethyl 2‐chloro‐3‐oxobutanoate, ethyl 2‐bromocyanoacetate, 2‐bromo‐5,5‐dimethylcyclohexan‐1,3‐dione, and bromomalononitrile. The boiling of 1a with ethyl 2‐bromocyanoacetate in mixture of ethanol and EtONa results in intramolecular cyclization and formation of thiazolo[3,2‐a]pyrimidin‐5‐one 3 . Interaction of 1a with 3‐chloropentane‐2,4‐dione and 2‐bromo‐1,3‐diphenylpropane‐1,3‐dione yielded corresponding S‐substituted thiopyrimidines 4a , 4b . In general, the products of 1b S‐alkylation are less prone to sulfur extrusion. Reaction of 1b with diethyl bromomalonate in the absence of EtONa stops at the S‐alkylation step, while in the presence of EtONa in ethanol or PPh₃ in dioxane 2‐(ethoxycarbonylmethyl)thio‐6‐phenyl‐1,3‐dihydropyrimidin‐4(1H)‐one 6 is formed exclusively. Molecular structure and crystal structure of 2‐(1,1‐diethoxycarbonylmethyliden)‐6‐methyl‐1,3‐dihydropyrimidin‐4(1H)‐one 2a are discussed.     

Syntheses of 2‐Unsubstituted 1H‐1,3‐Benzazaphospholes from N‐Formyl‐2‐bromoanilides

The phosphonylation of 2‐bromo‐formylanilides 1 with triethyl phosphite in the presence of preformed Pd(0)(triethyl phosphite)_n catalyst furnished 2‐phosphono‐formanilides 2 in good yields. Reduction with excess LiAlH₄ provided mainly N‐methyl‐2‐phosphinoanilines 3 and minor amounts of 1,2‐unsubstituted benzazaphospholes 4 . N‐Methyl‐1,3‐benzazaphospholes 5 were synthesized by the cyclocondensation of 3 with dimethylformamide dimethylacetal (DMFA). A more convenient route to 5 , avoiding the chromatographic separation of 4 , is the reduction of 1 to 2‐bromo‐N‐methylaniline 6 , followed by phosphonylation to 7 , LiAlH₄ reduction, and cyclization with DMFA. The coordination properties at σ²P of benzazaphospholes are characterized by structural data obtained by the crystal structure analysis of ( 5b )W(CO)₅.     

Synthesis and Fungicidal Activity of (1Z, 3Z)‐4,4‐Dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one O‐[2,4‐dimethylthiazole(or 4‐methyl‐1,2,3‐thiadiazole)]‐5‐carbonyl Oximes

A series of novel (Z)‐1‐tert‐butyl (or phenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐ethanone O‐[2,4‐dimethylthiazole (or 4‐methyl‐1,2,3‐thiadiazole) ?5‐carbonyl] oximes 5a – 5c and (1Z, 3Z)‐4,4‐dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one O‐[2,4‐dimethylthiazole (or 4‐methyl‐1,2,3‐thiadiazole)‐5‐carbonyl] oximes 6a – 6e were synthesized by the condensations of (Z)‐1‐tert‐butyl (or phenyl)‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐ethanone oximes 3 or (1Z, 3Z)‐4,4‐dimethyl‐1‐substitutedphenyl‐2‐(1H‐1,2,4‐triazol‐1‐yl)‐pent‐1‐en‐3‐one oximes 4 with 2,4‐dimethylthiazole‐5‐carbonyl chloride or 4‐methyl‐1,2,3‐thiadiazole‐5‐carbonyl chloride in the basic condition. Their structures were confirmed by IR, ¹H NMR, mass spectroscopy, and elemental analyses. The results of preliminary bioassays showed the title compounds 5 and 6 exhibited moderate to good fungicidal activities. For example, compound 6c possessed 86.4% inhibition against Fusarium oxysporum, and compound 6b exhibited 86.4 and 100% inhibition against Fusarium oxysporum and Cercospora arachidicola Hori at the concentration of 50 mg/L, respectively.     

Synthesis and Antifungal Activities of ω‐[4‐Aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thio]‐ω‐(1H‐1,2,4‐triazol‐1‐yl)acetophenones

New 4‐aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thiones 3 have been synthesized by the intramolecular cyclization of 4‐aryl‐1‐(1‐phenyl‐5‐methyl‐1,2,4‐triazol‐4‐formyl)thiosemicarbazides 2 with an 8% NaOH solution, and then 3 reacted with ω‐bromo‐ω‐(1H‐1,2,4‐triazol‐1‐yl)acetophenone to afford ω‐[4‐aryl‐5‐(1‐phenyl‐5‐methyl‐1,2,3‐triazol‐4‐yl)‐1,2,4‐triazol‐3‐thio]‐ω‐(1H‐1,2,4‐triazol‐1‐yl)‐acetophenones 4 . The preliminary biological test showed that the representative compounds possess some anti fungal activities.     

An Efficient Synthesis of 3′‐Amino‐3′‐deoxyguanosine from Guanosine

3′‐Amino‐3′‐deoxyguanosine was synthesized from guanosine in eight steps and 58% overall yield. The 2′,3′‐diol of 5′‐O‐[(tert‐butyl)diphenylsilyl]‐2‐N‐[(dimethylamino)methylidene]guanosine was reacted with α‐acetoxyisobutyryl bromide and treated with 0.5n NH₃ in MeOH to yield 9‐{2′‐O‐acetyl‐3′‐bromo‐5′‐O‐[(tert‐butyl)diphenylsilyl]‐3′‐deoxy‐β‐D ‐xylofuranosyl]‐2‐N‐[(dimethylamino)methylidene]guanine, which was reacted with benzyl isocyanate, NaH, and then 3.0n NaOH, and finally with Pd/C (10%) and HCO₂NH₄ in EtOH/AcOH to afford 3′‐amino‐3′‐deoxyguanosine.     

Synthese,Struktur, Elektrochemie und optische Eigenschaften von alkinylfunktionalisierten 1,3,2‐Diazaborolen und 1,3,2‐Diazaborolidinen

Syntheses, Structures, Electrochemistry and Optical Properties of Alkyne‐Functionalized 1,3,2‐Diazaboroles and 1,3,2‐Diazaborolidenes The reaction of 2‐bromo‐1,3‐ditert‐butyl‐2,3‐dihydro‐1H‐1,3,2‐diazaborole ( 3 ) with lithiated tert‐butyl‐acetylene and lithiated phenylacetylene affords the 2‐alkynyl‐functionalized 1,3,2‐diazaboroles 4 and 5 as a thermolabile colorless oil ( 4 ) or a solid ( 5 ). Similarly 2‐bromo‐1,3‐diethyl‐2,3‐dihydro‐1H‐1,3,2‐benzodiazaborole ( 6 ) was converted into the crystalline 2‐alkynyl‐benzo‐1,3,2‐diazaboroles 7 and 8 by treatment with LiC≡C–tBu or LiC≡CPh, respectively. 2‐Ethynyl‐1,3‐ditert‐butyl‐2,3‐dihydro‐1H‐1,3,2‐diazaborole ( 2 ) was metalated with tert‐butyl‐lithium and subsequently coupled with 2‐bromo‐1,3,‐ditert‐butyl‐2,3‐dihydro‐1H‐1,3,2‐diazaborole ( 3 ) to afford bis(1,3‐ditert‐butyl‐2,3‐dihydro‐1H‐1,3,2‐diazaborol‐2‐yl)acetylene ( 9 ) as thermolabile colorless crystals. Analogously coupling of the lithiated species with 6 or with 2‐bromo‐1,3‐ditert‐butyl‐1,3,2‐diazaborolidine ( 11 ) gave the unsymmetrically substituted acetylenes 10 or 12 , respectively, as colorless solids. Compounds 4 , 5 , 7 – 10 and 12 are characterized by elemental analyses and spectroscopy (IR, ¹H‐, ¹¹B{¹H}, ¹³C{¹H}‐NMR, MS). The molecular structures of 5 , 8 and 9 were elucidated by X‐ray diffraction analyses.     

Synthesis and Biological Screening of 2‐Substituted 5,6‐Dihydro‐5‐oxo‐ 4H‐1,3,4‐oxadiazine‐4‐propanenitriles and of Their Intermediates

To evaluate the effect of substituents on biological activities of electron‐rich N‐containing heterocycles, the variably 2‐substituted 5,6‐dihydro‐5‐oxo‐4H‐1,3,4‐oxadiazine‐4‐propanenitriles 26 – 33 were synthesized and evaluated for antibacterial, antifungal, and enzyme‐inhibition activities. The target compounds were obtained from alkyl 4‐ or 3‐hydroxy benzoates 1 and 2 , respectively, and from methyl indoleacetate 3 . The phenolic OH group of benzoates 1 and 2 were substituted with p‐toluenesulfonyl (→ 4 and 5 ), benzoyl (→ 6 and 7 ), and benzyl groups (→ 8 and 9 ) and then converted to 5,6‐dihydro‐5‐oxo‐4H‐1,3,4‐oxadiazine‐4‐propanenitriles. To establish structure‐activity relationships (SAR), a pharmacological screening of the intervening intermediates was also conducted, which revealed that the intermediate hydrazide 11 possesses significant antimicrobial and MAO‐A inhibiting properties and intermediates 12, 24, 28 , and 29 appreciable antifungal activities. Compound 7 inhibits α‐chymotrypsin.     

Reaction of Ketene Dithioacetals with Pyrazolylcarbohydrazide： Synthesis and Biological Activities of Ethyl 5-Amino-1-（5＇-methyl-1 ＇-t-butyl-4＇-pyrazolyl）carbonyl-3-methylthio-1 H-pyrazole-4-carboxylate

The title compound, C16H23N5O3S, ethyl 5-amino-1-(5‘-methyl-1‘-t-butyl-4‘-pyrazolyl)carbonyl-3-methylthio-1H-pyrazole-4-carboxylate (5) has been synthesized by the treatment of ethyl 2-cyano-3,3-dimethylthioacrylate with 1-t-butyl-5-methyl-4-hydrazinocarbonylpyrazole (4) in refluxed ethanol. The possible mechanism of the above reaction was also discussed. The results of biological test show that the title compound has fungicidal and plant growth regulation activities.     

Synthesis of 4‐alkyl‐1,2‐diphenyl‐3,5‐dioxopyrazolidines possessing aryl methylsulfonyl and sulfonamide pharmacophores for evaluation as selective cyclooxygenase‐2 (COX‐2) inhibitors

A group of 1,2‐diphenyl‐3,5‐dioxopyrazolidines possessing a methylsulfonyl ( 11 ) or sulfonamide ( 15 ) substituent at the para position of the N¹‐phenyl ring, in conjunction with a hydrogen, methyl or fluoro sub‐stituent at the para position of the N²‐phenyl ring, and a C‐4 n‐butyl, methyl or spiro‐cyclopropyl substituent were synthesized for evaluation as potential cyclooxygenase‐2 (COX‐2) selective inhibitor antiinflammatory agents. The title compounds 11 and 15 were synthesized using a four‐step and a three‐step reaction sequence, respectively. Thus, the acetic acid promoted condensation of a nitrosobenzene 5 with an aniline derivative ( 6, 12 ) gave the corresponding azobenzene product ( 8, 13 ) which was reduced with zinc dust in the presence of ammonium chloride to yield the corresponding hydrazobenzene ( 9, 14 ). Base‐catalyzed condensation of 9 and 14 with a malonyl dichloride ( 10 ) afforded the target 3,5‐dioxopyrazolidine product ( 11,15 ). 4‐n‐Butyl‐1‐(4‐methylsulfonylphenyl)‐2‐phenyl‐3,5‐dioxopyrazolidine ( 11a ) was a selective COX‐1 inhibitor (COX‐1 IC₅₀ = 8.48 μM). In contrast, 4‐n‐butyl‐1‐(4‐methylsulfonylphenyl)‐2‐(4‐tolyl)‐3,5‐dioxopyrazolidine ( 11b , COX‐2 IC₅₀ = 11.45 μM) and 4‐n‐butyl‐1‐(4‐methylsulfonylphenyl)‐2‐(4‐fluorophenyl)‐3,5‐dioxopyrazoli‐dine ( 11c , COX‐2 IC₅₀ = 9.86 μM) were about 46‐fold and 20‐fold less selective COX‐2 inhibitors respectively, relative to the reference drug celecoxib.     

Synthesis and isolation of bromo‐β‐carbolines obtained by bromination of β‐carboline alkaloids

β‐Carbolines ( 1–5 ) undergo electrophilic aromatic substitution with N‐bromosuccinimide under different experimental conditions. Although 6‐bromo‐nor‐harmane ( la ) obtained by bromination of nor‐harmane ( 1 ) was isolated and fully characterized sometime ago, the other bromoderivatives of nor‐harmane ( 1b‐1e ) and harmane ( 2a‐2e ) were partially described as part of the reaction mixtures. The preparation and subsequent isolation, purification and full characterization of 1b, 1c, 1d, 1e, 2a, 2b, 2c, 2d, 2e are reported (mp, R _f, ¹H‐nmr, ¹³C‐nmr and ms) together with the preparation, isolation and charaterization, for the first time, of the bromoderivatives obtained from harmine ( 3a‐3e ), harmol ( 4a, 4b ) and 7‐acetylharmol ( 5a‐5c ). As brominating reagent N‐bromosuccinimide and N‐bromosuccinimide‐silica gel in dichloromethane and in chloroform as well as the β‐carboline ‐ N‐bomosuccinimide solid mixture have been used and their uses have been compared. Semiempirical AMI and PM3 calculations have been performed in order to predict reactivity in terms of the energies of HOMO, HOMO‐LUMO difference and in terms of the charge density of β‐carbolines ( 1–5 ) and bromo‐β‐carbolines ( 1a‐1e, 2a‐2e, 3a‐3e, 4a, 4b, 5a, 5b and 5c ) (Scheme 1). Theoretical and experimental results are discussed briefly.     

3/4‐phenylene bisheterocycles from ring transformation reaction of sydnone derivatives: Synthesis of 3‐[3/4‐heterocyclyl]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones from 3/4‐acetylphenylsydnones and their biological properties

The bifunctional 3/4‐[acetyl]phenylsydnones 1a, 1b were subjected to a one‐pot ring conversion to 3‐[3/4‐acetyl]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 2a, 2b , which on further bromination yielded the 3‐[3/4‐bromoacyl]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 3a, 3b . Reaction of these compounds with thiourea yielded the 3‐[3/4‐(2‐aminothiazol‐4‐yl)]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 4a, 4b . The other thiazole derivatives 5a, 5b–7a, 7b were prepared by using thiosemicarbazide, thioacetamide, and thiobenzamide, respectively. In another reaction of the bromoacetyl compounds ( 3a, 3b ) with 2‐aminopyridine and 2‐aminothiazole, the fused biheterocyclic compounds 3‐[3/4‐imidazo‐[1,2‐a]pyridine‐2‐yl]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 8a, 8b and 3‐[3/4‐imidazo‐[2,1‐b]‐thiazol‐6‐yl]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 9a, 9b were obtained. The 3‐[3/4‐(benzofuran‐2‐carbonyl)]phenyl‐5‐methyl‐3H‐[1,3,4]‐oxadiazol‐2‐ones 10a, 10b were obtained by treatment of compounds 3a, 3b with o‐hydroxy benzaldehyde. Most of these compounds exhibited antifungal activity greater than the reference drugs used. © 2007 Wiley Periodicals, Inc. Heteroatom Chem 18:50–54, 2007; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20255     

Synthesis,properties and solid state structure of 5‐diphenylphosphino‐2‐hydroxy‐1,3‐xylyl‐18‐crown‐5

5‐Diphenylphosphino‐2‐hydroxy‐1,3‐xylyl‐18‐crown‐5 has been synthesized from 5‐bromo‐2‐hydroxy‐18‐crown‐5 by reacting it in sequence at low temperature with n‐butyl lithium and methyl diphenylphosphonite. The phosphorous donor properties of this phenol phosphine (OH derivative) and the corresponding phenoxide (O^? derivative) have been studied in the presence and absence of alkali metal ions by determining the frequencies of the A₁ ν(CO) bands of Ni(CO)₃L complexes. For the OH and O^? derivatives, the latter generated by addition of CsOH to the former, the ν(CO) bands are observed at 2067.6 and 2063.4 cm^?1, respectively, providing the trend predicted by Hammett parameters for OH and O^? substituents. Addition of Na⁺ or K⁺ to the OH derivative has little effect on this stretching frequency, but the former ion shifts the O^? derivative band to 2067.7 cm^?1 A solid state structure has been obtained of the OH derivative, and two independent molecules were found in the unit cell. Both have a single water molecule hydrogen bonded to two across‐ring oxygen atoms and the phenol hydrogen. The crown ether ring has the usual gauche and anti arrangements for the C‐C and C? O bonds.