Darstellung von Bis‐(2‐chlorethyl)amino‐substituierten Diazaphosphorinonen. Reversible oxidative Addition von Hexafluoraceton an σ3λ3‐Phosphor‐Verbindungen. Synthese von σ5λ5‐Spirophosphoranen und deren Zersetzung

Synthesis of Bis‐(2‐chloroethyl)amino‐substituted Diazaphosphorinones. Reversible Oxidative Addition of Hexafluoroacetone to σ³λ³‐Phosphorus Compounds. Synthesis of σ⁵λ⁵‐Spirophosphoranes and their Decomposition The reaction of 1‐methyl‐pyrido[3,2‐e]‐3,1‐oxazin‐2,4‐dione ( 1 ) with benzylamines led to the aminonicotinic acid amides 2 – 4 . Their reaction with phosphorus trichloride furnished the P‐chloro‐pyridodiazaphosphorinones 5 – 7 , which, upon reaction with bis‐(2‐chloroethyl) ammonium chloride/triethylamine, were converted into the P‐bis‐(2‐chloroethyl)amino‐substituted pyridodiazaphosphorinones 8 – 10 . The P‐chloro‐benzodiazaphosphorinone 11 was allowed to react with 2‐chloroethylammonium chloride/triethylamine to form the 2‐chloroethylamino‐substituted derivative 12 . The σ³‐diazaphosphorinones 8 , 9 , 12 and 13 were oxidized with the urea‐hydrogen peroxide‐(1 : 1)‐adduct to the corresponding phosphoryl derivatives 14 – 17 . The oxidative addition of hexafluoroacetone (HFA) to the σ³‐diazaphosphorinone 18 led, with abstraction of methyl chloride, to the tricyclic phosphorane 19 b . The spirophosphoranes 21 – 23 were formed by reaction of compounds 8 , 9 and 13 with HFA. NMR‐studies were made on the decomposition of the bicyclic phosphoranes 20 a , 22 and 23 . The oxidative addition of HFA to diazaphosphorinones was found to be reversible. Single crystal X‐ray determinations were conducted on compounds 17 and 19 b . They confirm the expected connectivity. Compound 17 was found to exhibit short C–H‥ O‐hydrogen bonds (H…O 234 pm). Compound 19 crystallises as two independent molecules which differ, e. g., in the orientation of the chloroethyl groups.     

Synthesis of Bis{(S‐methyl)azolespoly(ethylene oxide)} from 3,6‐dioxa‐1,8‐octanedithiol

Bis(1,3,4‐oxadiazoles) 4 , 5 and bis(1,2,4‐triazoles) 6a , 6b have been prepared from 3,6‐dioxa‐1,8‐octanedithiol 1 through a multistep reaction sequence. Compound 4 reacted with the appropriate alkyl halide in the presence of potassium carbonate in refluxing acetone to give the corresponding bis(S‐alkylated‐1,3,4‐oxadiazoles) 7a , 7b . The title compound 8 was prepared by condensing 4 with benzoyl bromide in the presence of triethylamine. Further, 6,9‐dioxa‐3,12‐dithiotetradecanedihydrazide 3 was converted to bis{N′‐(phenylaminocarbonyl) hydrazides} and bis{N′‐(phenylaminocarbonothioyl)hydrazides} 9a , 9b using phenylisocyanate and phenylthioisocyanate, respectively, which underwent cyclization in alkaline medium to produce 6,9‐dioxa‐3,12‐dithiotetradecane bis(4‐phenyl‐2,4‐dihydro‐3H‐1,2,4‐triazol‐3‐one) and their 3‐thio analogs 10a , 10b . The new compounds 4 , 5 , 6 , 7 , 8 , 9 , 10 were characterized by their IR, ¹H‐NMR, ¹³C‐NMR, MS, and elemental analyses.     

The Synthesis of 1,4‐Bis[N‐(4/6‐Substituted Benzothiazole‐2‐yl)‐N′‐Glycosylguanidino]Benzenes

The starting material O‐protected glycosyl isothiocyanate ( 1?3 ) was refluxed with 1,4‐diaminobenzene in CHCl₃ under nitrogen atmosphere to give 1,4‐bis(N‐glycosyl)thioureidobenzene ( 4?6 ). Then 1,4‐bis[N‐(4/6‐substituted benzothiazole‐2‐yl)‐N′‐glycosylguanidino]benzenes ( 8a?8e , 9a?9e , 10a?10e ) were obtained in good yield by reaction of compounds ( 4?6 ) with 2‐amino‐4/6‐benzothizoles ( 7a?7e ) and HgCl₂ in the presence of TEA in DMF. The structures of all 18 new compounds were confirmed by IR, ¹H NMR, LC‐MS and elemental analysis. The bioactivity of anti‐HIV‐1 protease (HIV‐1 PR) and against angiotensin converting enzyme (ACE) have been evaluated.     

Synthesis and Antimicrobial Activities of Novel Series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one Derivatives

In the present investigation, a novel series of 3‐(4‐(2‐substituted thiazol‐4‐yl)phenyl)‐2‐(4‐methyl‐2‐substituted thiazol‐5‐yl)thiazolidin‐4‐one derivatives were synthesized by condensation of 2‐substituted‐4‐methylthiazole‐5‐carbaldehyde with 4‐(2‐substituted thiazol‐4‐yl)benzenamine followed by cyclo‐condensation with thioglycolic acid in toluene. All the newly synthesized compounds were characterized by spectral (IR, ¹H NMR, ¹³C NMR, and Mass) methods. The title compounds were screened for quantitative antibacterial activity (minimal inhibitory concentration). All compounds 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h and 8a , 8b , 8c , 8d , 8e , 8f , 8g , 8h show moderate to good antimicrobial activity, whereas compounds ( 7a , 7b , 7c , 7d , 7e , 7f , 7g , 7h ) also show moderate antifungal activity.     

Synthesis and antimicrobial activity of 8‐alkylcarbamato‐16H‐dinaphtho [2,1‐d:1′,2′‐g] 1,3,2‐dioxaphosphocin 8‐oxides

A new family of phosphorus heterocycles, namely 8‐alkylcarbamato‐16H‐dinaphtho‐[2,1‐d: 1′,2′‐g] 1,3,2‐dioxaphosphocin 8‐oxides ( 4a–j ) has been obtained by reaction of bis(2‐hydroxy‐1‐naphthyl)methane ( 3 ) with a series of dichlorophosphosphinyl carbamates ( 2a–j ) in dry toluene in the presence of triethylamine at 40–45°C. The intermediates 2a–j were obtained by the addition of alcohols/thiol to isocyanatophosphonic dichloride ( 1 ) at −10°C in dry toluene. The structures of the title compounds were confirmed by the elemental analyses, IR, ¹H, ¹³C, and ³¹P NMR spectra. The FAB mass spectrum of one member of the family is discussed. These compounds were found to possess good antimicrobial activity. © 2001 John Wiley & Sons, Inc. Heteroatom Chem 12:16–20, 2001     

A series of 1‐[2‐aryl‐1‐diazenyl]‐3‐({3‐[2‐aryl‐1‐diazenyl]perhydrobenzo[d]imidazol‐1‐yl}methyl)perhydrobenzo[d]imidazoles. Synthesis and characterization

Reaction of diazonium salts with solutions of 1,2‐diaminocyclohexane mixed with formaldehyde affords the 1‐[2‐aryl‐1‐diazenyl]‐3‐({3‐[2‐aryl‐1‐diazenyl]perhydrobenzo[d]imidazol‐1‐yl}methyl)perhydrobenzo‐[d]imidazoles ( 6 ), a new series of bis‐triazenes with different connectivity than any previous type of bis‐triazene reported. The products have been characterized principally by NMR and IR spectroscopy, elemental analysis and unequivocally by X‐ray crystallography. The methylene protons of the perhydroimidazole rings are diastereotopic giving rise to a doublet of doublets pattern in the ¹H NMR spectra. However, detailed analysis of the NMR spectra shows that there is more than one set of doublet‐of‐doublet signals, suggesting the presence of different rotameric forms of the products. The ¹³C NMR spectral assignments were assisted by COSY and DEPT experiments with selected compounds.     

Symmetrical Bis‐Phosphorus Compounds and Macrocycles with two 1,3,2‐Benzodiazaphosphorinone Units – Oxidation and X‐Ray Structure Analysis of Selected Compounds

The hydrolysis of 1,2‐bis(5,6‐benzo‐1‐methyl‐2‐chloro‐1,3,2‐diazaphosphorin‐4‐on‐3‐yl)ethane ( 1 ) and its 1,3‐propane derivative ( 2 ) with excess water led, without decomposition, to the formation of the bis‐phosphoryl compounds 3 and 4 . Reaction of 1 and 2 with bis(trimethylsiloxy)ethane formed the symmetrical macrocycles 5 and 6 , which could readily be oxidized by (H₂N)₂C(:O) · H₂O₂ or elemental sulfur, leading to the formation of the phosphoryl compounds 7 and 10 , and the thiophosphoryl derivatives 9 and 11 , respectively. The influence of the ring size on the reaction rate of the oxidation was investigated. For the sulfurization of 6 , the stepwise addition of sulfur to phosphorus was proved by NMR spectroscopy. All compounds exist as single conformers in common organic solvents such as toluene, diethyl ether, dichloromethane or chloroform. For compounds 7 (dichloromethane solvate) and 9 , single crystal X‐ray structure analyses were conducted; both diastereomeric molecules were shown to display RR/SS configuration. In both structures one short non‐classical hydrogen bond was observed.     

Alkyl‐Tethered Bis‐Phosphoryl Compounds with two 1,3,2‐Benzodiazaphosphorinone Units; Oxidation,Complexation, and X‐Ray Structure Analysis of Selected Compounds

The reaction of the bis‐chlorophosphines 1 a – 1 d with bis(2‐chloroethyl)amine hydrochloride in the presence of triethylamine and with various trimethylsilylamines led to a new class of bis‐phosphorus ligands 2 a – 2 c and 3 a – 3 g . ³¹P‐NMR studies suggested that the bis‐phosphorus ligands undergo rotation reactions about the alkyl bridge in polar solvents. Compounds 2 a – 2 c showed initially only one sharp singlet each in their ³¹P‐NMR spectra. After a few days at room temperature, two signals were observed. Similar results were observed for 3 a – 3 g . In the solid state, the two phosphorus atoms in 2 c are not equivalent, as was confirmed by the observation of two signals in the solid state ³¹P‐NMR spectrum. Oxidation reactions of 2 a – 2 c by the hydrogen peroxide‐urea 1 : 1 adduct (NH₂)₂C(:O) · H₂O₂ led to the formation of the corresponding phosphoryl compounds 4 a – 4 c . Reaction of 2 a and 3 a with Pt[COD]Cl₂ (COD = 1.5‐Cyclooctadiene) furnished the complexes 5 and 6 . The NMR spectra suggested that the two chlorine atoms are in cis position. X‐ray structure analyses were conducted for 2 a , which exhibits twofold symmetry; 2 c , which is linked into dimers by hydrogen bonds C–H…O; and 6 , confirming the cis configuration.     

5‐Chloro‐3‐methylthio‐1,2,4‐thiadiazol‐2‐ium chlorides as useful synthetic precursors to a variety of 6aλ4‐thiapentalene systems

Title salts 3 were easily obtained by treatment of formimidoyl isothiocyanates 1 with a twofold excess of methanesulfenyl chloride. They showed interesting chemical behavior toward several nitrogen and carbon nucleophiles. Substitution reactions with isothioureas and acetamide in the presence of triethylamine gave the 1H, 6H‐6aλ⁴‐thia‐1,3,4,6‐tetraazapentalenes 7 and 6H‐6aλ⁴‐thia‐1‐oxa‐3,4,6‐triazapentalene 9 , respectively. Addition of p‐toluidine furnished the 5‐imino‐thiadiazole derivatives 10 , which reacted further with diverse heterocumulenes to yield the corresponding thiatriaza‐ and tetraazapentalene species 11 . The N,N′‐bis(1,2,4‐thiadiazol‐5‐ylidene)diaminobenzenes 13 were also prepared and reacted with phenyl isothiocyanate. Two stable rotational isomers were separated for the 1,2‐phenylene product 14b . Other π‐hypervalent sulfur compounds 16 were synthesized under similar conditions from salts 3 and methyl cyanoacetate or dimethyl malonate. The structural assignments were discussed on the basis of IR and NMR spectroscopic data and received additional support from X‐ray analysis of substrate 16a . © 2003 Wiley Periodicals, Inc. Heteroatom Chem 14:95–105, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/hc.10106     

Three New, 1‐Oxygenated ent‐8,9‐Secokaurane Diterpenes from Croton kongensis

Three new ent‐8,9‐secokaurane diterpenes, kongensins A–C ( 1 – 3 ), were isolated from the aerial parts of Croton kongensis, together with two known compounds, rabdoumbrosanin ( 4 ) and (7α,14β)‐7,14‐dihydroxy‐ent‐kaur‐16‐en‐15‐one ( 5 ). The structures of the new compounds were elucidated by HR‐MS as well as in‐depth 1D‐ and 2D‐NMR analyses. Compounds 1 – 3 showed an unusual oxygenation pattern, with an AcO or OH group at C(1), in combination with a Δ⁸⁽¹⁴⁾ unsaturation ( 1 ) or an 8,14‐epoxide function ( 2, 3 ).     

Synthesis and Spectral Characterization of Novel Bis‐thiazole Derivatives via Ring Closure of Benzo[d]thiazol‐2‐amine,Various α‐Haloketones,and S‐Nucleophiles

Novel functionalized bis‐thiazole derivatives ( 4a–d , 9a , b , 13a–e , and 16a–d ) were synthesized in good to excellent yields (70–90%) via the ring closure of benzo[d ]thiazol‐2‐amine and various α‐haloketones in the presence of carbon disulfide or aryl isothiocyanates as S‐nucleophiles. The structures of newly synthesized compounds were characterized by IR, ¹H NMR, ¹³C NMR, elemental analysis, and mass spectroscopy techniques.     

Synthesis and Reactions of Some New Benzo[a]phenothiazine‐3,4‐dione Derivatives

The reaction of 2,3‐dihydro‐2,3‐epoxy‐1,4‐naphthoquinone ( 4 ) with substituted anilines furnished the corresponding benzo[fused]heterocyclic derivatives 5 , 6 , 6a , 6b , 7 , 8 . Furthermore, treatment of benzo[a]phenothiazine derivative 7 with halo compounds, namely, ethyl bromoacetate, phenacyl bromide, dibromoethane, or chloroacetone afforded ether derivatives 11 , 12 , 13 , 14 , respectively. Moreover, the reaction of 11 with o‐substituted aniline gave the corresponding benzo[a]phenothiazin‐5‐one derivatives 15 , 16 , 17 and benzo[d][1,3]oxazin‐4‐one 18 , respectively. Finally, the chromenone derivative 19 was synthesized via the reaction of ester derivative 11 with salicyaldhyde in refluxing pyridine. The newly synthesized compounds were characterized by spectroscopic measurements (IR, ¹H NMR, ¹³C NMR, and mass spectra).     

Synthesis and Fluorescent Properties of 2‐Arylamino‐5‐(3‐Aryl‐1‐Phenyl‐Pyrazol‐4‐Yl)‐1,3,4‐Thiadiazoles

A series of novel pyrazolyl‐substituted 1,3,4‐thiadiazole derivatives ( 6a‐6d, 7a‐7d, 8a‐8d ) were prepared by cyclization of the intermediate 3‐aryl‐l‐phenyl‐pyrazol‐4‐ylformaldehyde 4′‐phenylthiosemicarbazones with 0.5 M ferric chloride solution. The structures of the new compounds were confirmed by IR, ¹H NMR and elemental analysis. Simultaneously, the compounds were detected by fluorescence spectrophotometer and had preferable fluorescence activity.     

Syntheses,Structure, Electrochemistry,and Optical Properties of 1,3‐Diethyl‐2,3‐dihydro‐1‐H‐1,3,2‐pyrido‐[4,5‐b]‐diazaboroles

Reaction of 2,5‐bis(dibromoboryl)thiophene ( 4 ) or 1,4‐bis(dibromoboryl)benzene ( 6 ) with two equivalents of N,N′‐dilithiated 2,3‐diaminopyridine ( 3 ) led to the generation of the pyridodiazaboroles 5 and 7 in which the two diazaborole rings are linked by 2,5‐thiophen‐diyl or 1,4‐phenylene units via the boron atom. The novel compounds were characterized by elemental analyses and spectroscopy (¹H‐, ¹¹B‐, ¹³C‐NMR, MS, and UV‐VIS). The molecular structure of 5 was elucidated by X‐ray diffraction. Cyclovoltammograms of 5 and 7 show two irreversible oxidation waves at 0.76 and 0.73 V, respectively vs Fc/Fc⁺. The novel compounds display intense blue luminescence with Stokes shifts of 76 and 74 nm and relative quantum yields of 39 and 43 % vs Coumarin 120 (Φ = 50 %).     

Synthesis and biological study of novel methylene‐bis‐chalcones and substituted methylene‐bis‐pyrimidines/pyrimidinones

A series of novel methylene‐bis‐chalcones was prepared by the reaction of 5,5′‐methylene‐bis‐salicylaldehyde with different acetophenones, subsequent treatment of methylene‐bis‐chalcones with urea/thiourea gave the corresponding methylene‐bis‐pyrimidinones/methylene‐bis‐mercaptopyrimidines in good yields. Characterization of the new compounds has been done by means of IR, ¹H NMR, MS and elemental analysis. The antibacterial, antitubercular and antifungal activity of the compounds has also been evaluated.     

Synthesis of New Metal‐Free 1,4,8,11‐Tetraaza[14]annulene Derivatives Using 2‐Heteroaryl‐substituted Trimethinium Salts

The reaction of 2‐heteroaryl‐substituted trimethinium salts (A, B, and C) with aromatic 1,2‐diamines ( a , b , c , d , and e ) in acetonitrile/acetic acid leads to 6,13‐disubstituted 1,4,8,11‐tetraaza[14]annulene derivatives ( 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 ). The UV–vis spectral behavior of these compounds was examined in acetonitrile. Elemental analysis, IR, ¹H‐NMR, ¹³C‐NMR, and mass spectra confirm the molecular structure of the newly synthesized compounds.     

Diselenastanna‐, ‐sila‐ and ‐carbacycles with an annelated dicarba‐closo‐dodecaborane(12) unit

The reactions of the 1,2‐diselenolato‐1,2‐dicarba‐closo‐dodecaborane(12) dianion 1 with diorganoelement(IV) dichlorides (Ph₂CCl₂, Me₂SiCl₂, Ph₂SiCl₂, Me₂SnCl₂, Ph₂SnCl₂) gave novel five‐member heterocycles along with other products. The molecular structures of the five‐member rings containing CPh₂ ( 2 ) and SnPh₂ ( 9 ) moieties between the selenium atoms were determined by X‐ray analyses. In the case of the chlorosilanes, the analogous five‐member ring containing the SiPh₂ unit ( 4 ) could be identified in mixtures. The expected reaction was accompanied by rearrangement leading to formation of another five‐member ring 6 containing the Ph₂Si? Se? Se moiety. Oxidative addition of the five‐member heterocycles containing tin ( 7, 9 ) to ethene‐bis(triphenylphosphane)platinum(0) gave at low temperature the bis(triphenylphosphane)platinum(II) complexes 12 and 13 , where the Pt(PPh₃)₂ fragment had been inserted into one of the Sn? Se bonds. Extensive decomposition of these complexes was observed above ? 20 °C. The proposed solution‐state structures of the new compounds are supported by multinuclear magnetic resonance data (¹H, ¹¹B, ¹³C, ²⁹Si, ³¹P, ⁷⁷Se, ¹¹⁹Sn and ¹⁹⁵Pt NMR). Copyright © 2007 John Wiley & Sons, Ltd.     

Synthesis and Bioactivity of Novel Bis‐heterocyclic Compounds Containing Pyrazole and Oxadiazoline

Nucleophilic addition of the starting material 3‐aryl‐1‐phenyl‐4‐formylpyrazoles ( 1～3 ) and 4‐substituted aryloxyacetyl hydrazine ( 4a～4e ) afford hydrazone compounds containg pyrazolyl ( 5a～5e, 6a～6e, 7a～7e ) in the ethanol. These adducts were refluxed in Ac₂O and furnished a series of novel bis‐hetero‐cyclic compounds. ( 8a～8e, 9a～9e, 10a～10e ) via cyclic reaction. The structures of all newly synthesized compounds were established by IR, ¹H NMR, MS and elemental analysis. New compounds conducted preliminary tests of antibacterial activities about Fusarium oxyaporium, Verticillium dahliae, Rhizoctonia solani, Pychium aphanidermatum, Alternaria solani, Sclerotinia sclerotiorum. The results showed that the inhibiting rate of the bis‐heterocyclic compounds ( 8a～8e, 9a～9e, 10a～10e ) was higher than the pyrazolyl hydrazones ( 5a～5e, 6a～6e, 7a～7e ) obviously.     

Stepwise Strategy to Cyclometallated PtII Complexes with N‐Heterocyclic Carbene Ligands: A Luminescence Study on New β‐Diketonate Complexes

The imidazolium salt 3‐methyl‐1‐(naphthalen‐2‐yl)‐1H‐imidazolium iodide ( 2 ) has been treated with silver(I) oxide and [{Pt(μ‐Cl)(η³‐2‐Me‐C₃H₄)}₂] (η³‐2‐Me‐C₃H₄=η³‐2‐methylallyl) to give the intermediate N‐heterocyclic carbene complex [PtCl(η³‐2‐Me‐C₃H₄)(H$\widehat{CC}$ *‐κC*)] ( 3 ) (H$\widehat{CC}$ *‐κC*=3‐methyl‐1‐(naphthalen‐2‐yl)‐1H‐imidazol‐2‐ylidene). Compound 3 undergoes regiospecific cyclometallation at the naphthyl ring of the NHC ligand to give the five‐membered platinacycle compound [{Pt(μ‐Cl)($\widehat{CC}$ *)}₂] ( 4 ). Chlorine abstraction from 4 with β‐diketonate Tl derivatives rendered the corresponding neutral compounds [Pt($\widehat{CC}$ *)(L‐O,O′)] {L=acac (HL=acetylacetone) 5 , phacac (HL=1,3‐diphenyl‐1,3‐propanedione) 6 , hfacac (HL=hexafluoroacetylacetone) 7 }. All of the compounds ( 3 – 7 ) were fully characterized by standard spectroscopic and analytical methods. X‐ray diffraction studies were performed on 5 – 7 , revealing short Pt?Pt and π–π interactions in the solid‐state structure. The influence of the R‐substituents of the β‐diketonate ligand on the photophysical properties and the use of the most efficient emitter, 5 , as phosphor converter has also been studied.     

Microwave‐assisted Synthesis,Characterization, and Density Functional Theory Study of Biologically Active Ferrocenyl Bis‐pyrazoline and Bis‐pyrimidine as Organometallic Macromolecules

Organometallic macromolecules such as ferrocenyl bis‐pyrazoline ( 2 , 3 ) and bis‐pyrimidine ( 4 , 5 ) derivatives were synthesized by reacting ferrocenyl bis‐chalcone 1 with thiosemicarbazide/phenylhydrazine/guanidine hydrochloride/thiourea, respectively, under microwave irradiation. Ferrocenyl bis‐chalcone 1 was synthesized by reacting acetyl ferrocene with terephthalaldehyde. Synthesized compounds were characterized by using IR, ¹H NMR, ¹³C NMR, EI‐MS, and elemental analysis. In vitro antibacterial activity against two Gram‐negative and two Gram‐positive bacteria was determined by the disc diffusion assay. Moreover, minimum inhibition concentrations were also measured with reference to chloramphenicol. Thioamide functionally containing ferrocenyl bis‐pyrazoline derivative 2 shows the best antibacterial activity on Escherichia coli and Salmonella typhimurium, among all tested compounds including the reference drug chloramphenicol. The structure–activity relationship is also developed by using computational calculations with density functional theory (DFT)/B3LYP method.