(Benzene‐1,3,5‐triyl)tris[phosphine] (C6H3(PH2)3) and (Benzene‐1,3,5‐triyl)tris[phosphonic Acid] (C6H3[P(O)(OH)2]3). Absence of Hydrogen Bonding in Solid Primary Phosphines

The prolonged photo‐Arbuzov reaction (3 weeks, Hg lamp) of 1,3,5‐trichloro‐benzene with a large excess of trimethyl phosphite (as a solvent) at 50° gives moderate yields of dimethyl (3,5‐dichlorophenyl)phosphonate ( 1 ; 14.5%), tetramethyl (5‐chloro‐1,3‐phenylene)bis[phosphonate] ( 2 ; 35.4%), and hexamethyl (benzene‐1,3,5‐triyl)tris[phosphonate] ( 3 ; 30.1%). The products can be separated by fractional distillation. Acid hydrolysis of the esters gives almost quantitative yields of the corresponding phosphonic acids 4 – 6 . Reduction of the esters 1 – 3 by LiAlH₄ in tetrahydrofuran affords the primary phosphines (3,5‐dichlorophenyl)phosphine ( 7 ; 46.5%), (5‐chloro‐1,3‐phenylene)bis[phosphine] ( 8 ; 34.5%) and (benzene‐1,3,5‐triyl)tris[phosphine] ( 9 ; 25.2% yield). In the crude reduction products from 2 (preparation of 8 ) and from 3 (preparation of 9 ), (3‐chlorophenyl)phosphine and (1,3‐phenylene)bis[phosphine], respectively, are observed as by‐products. All compounds are characterized by standard analytical, spectroscopic, and (for 1, 7 , and 8 ) structural techniques. The arrangement of the molecules in the crystal structures of 7 and 8 suggest that H‐bonding between the primary arylphosphines is virtually insignificant for the packing of the components. This is in marked contrast to the importance of H‐bonding for the supramolecular chemistry of arylamines. The new primary polyphosphines and polyphosphonic acids are to be employed in the construction of extended arrays.     

Novel Compounds with a Viologen Skeleton and N‐Heterocycles on the Peripheries: Electrochemical and Spectroscopic Properties

The present article deals with novel compounds comprising a redox‐active group as core and a nucleobase in the peripheries, linked covalently via a spacer. The new derivatives 1,1′,1″‐(benzene‐1,3,5‐triyltrimethanediyl)tris{1′‐[3‐(3,4‐dihydro‐5‐methyl‐2,4‐dioxopyrimidin‐1(2H)‐yl)propyl]‐4,4′‐bipyridinium} hexafluorophosphate ( 1 ), 1,1′,1″‐(benzene‐1,3,5‐triyltrimethanediyl)tris{1′‐[2‐(4‐chloro‐7H‐pyrrolo[2,3‐d]pyrimidine‐7‐yl)ethyl]‐4,4′‐bipyridinium} hexachloride ( 2a ) 1

1 The numbering of the pyrrolo[2,3‐d]pyrimidine system follows the IUPAC rules and is different from that of the purine ring system.

, and 1,1′,1″‐(benzene‐1,3,5‐triyltrimethanediyl)tris{1′‐[2‐(2‐amino‐4‐chloro‐7H‐pyrrolo[2,3‐d]pyrimidine‐7‐yl)ethyl]‐4,4′‐bipyridinium} hexabromide ( 2b )¹) were synthesized by nucleobase‐anion alkylation and linked to the 4,4′‐bipyridinium core. UV and CV analyses of these compounds were performed and revealed significantly different properties.     

Novel Benzyl‐ or 4‐Cyanobenzyl‐Substituted N‐Heterocyclic (Bromo)(carbene)silver(I) and (Carbene)(chloro)gold(I) Complexes: Synthesis and Preliminary Cytotoxicity Studies

N‐Heterocyclic carbene (NHC) complexes bromo(1,3‐dibenzyl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene)silver(I) ( 2a ), bromo[1‐(4‐cyanobenzyl)‐3‐methyl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene]silver(I) ( 2b ), and bromo[1‐(4‐cyanobenzyl)‐3‐methyl‐1,3‐dihydro‐2H‐benzimidazol‐2‐ylidene]silver(I) ( 2c ) were prepared by the reaction of 1,3‐dibenzyl‐1H‐imidazol‐3‐ium bromide ( 1a ), 3‐(4‐cyanobenzyl)‐1‐methyl‐1H‐imidazol‐3‐ium bromide ( 1b ), and 3‐(4‐cyanobenzyl)‐1‐methyl‐1H‐benzimidazol‐3‐ium bromide ( 1c ), respectively, with silver(I) oxide. NHC Complexes chloro(1,3‐dibenzyl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene)gold(I) ( 3a ), chloro[1‐(4‐cyanobenzyl)‐3‐methyl‐1,3‐dihydro‐2H‐imidazol‐2‐ylidene]gold(I) ( 3b ), and chloro[1‐(4‐cyanobenzyl)‐3‐methyl‐1,3‐dihydro‐2H‐benzimidazol‐2‐ylidene]gold(I) ( 3c ) were prepared via transmetallation of corresponding (bromo)(NHC)silver(I) complexes with chloro(dimethylsulfido)gold(I). The complex 3a was characterized in two polymorphic forms by single‐crystal X‐ray diffraction showing two rotamers in the solid state. The cytotoxicities of all three bromo(NHC)silver(I) complexes and three (chloro)(NHC)gold(I) complexes were investigated through 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyl‐2H‐tetrazolium bormide (MTT)‐based preliminary in vitro testing on the Caki‐1 cell line in order to determine their IC₅₀ values. (Bromo)(NHC)silver(I) complexes 2a – 2c and (chloro)(NHC)gold(I) complexes 3a – 3c were found to have IC₅₀ values of 27±2, 28±2, 34±6, 10±1, 12±5, and 12±3 μM , respectively, on the Caki‐1 cell line.     

Synthesis,Characterization, and Screening for Anti‐inflammatory and Antimicrobial Activity of Novel Indolyl Chalcone Derivatives

Because of the great biological importance of substituted indole derivatives, in the present study, a series of pyrazolylindole, thiazolylindole, and pyrimidinylindole derivatives have been synthesized with good yield. The precursor indolyl chalcone 2a – d was prepared by reaction of 3‐chloro‐1H‐indole‐2‐carbaldehyde 1 with different ketones. Then, compounds 3b – d , 4 , and 5a – d have been synthesized by the reaction of chalcones 2a – d with hydrazine, phenylhydrazine, and thiosemicarbazide. When the chalcone derivative 2b subjected to react with hydroxylamine hydrochloride gave isoxazolylindole derivative 6b . N‐thiazolidine pyrazolyl indole 7 was obtained by reacting compound 5a with ethyl chloroacetate. On the other hand, when chalcone derivative 2b allowed to react with urea and thiourea gave the corresponding pyrimidinylindole derivatives 8 and 9 . Finally, when chalcone derivative 2b reacted with ethyl cyanoacetate or malononitrile gave pyridinylindole derivatives 10 and 11 . The structures of the all synthesized compounds were elucidated on the basis of spectral analysis infrared, NMR, and mass spectroscopy. Some of the synthesized compounds were screened for their antimicrobial and anti‐inflammatory activity. Compound 4b was the highest antibacterial activity against all strains of bacteria with values higher than those of the corresponding reference antibiotics (ciprofloxacin and levofoxacin, respectively) and almost the same as (gemifloxacin, moxifloxacin, clindamycin, gentamycin, and streptomycin). Compounds 4 , 5 , 6 , and 7 showed high anti‐inflammatory activity compared with the standard drug indomethacin.     

Quinolone analogues 2. A facile synthesis of novel 3‐substituted 1‐alkyl‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxalines

The reaction of the 2‐(1‐alkylhydrazino)‐6‐chloroquinoxaline 4‐oxides 1a,b with diethyl acetone‐dicarboxylate or 1,3‐cyclohexanedione gave ethyl 1‐alkyl‐7‐chloro‐3‐ethoxycarbonylmethylene‐1,5‐dihydropyridazino[3,4‐b]quinoxaline‐3‐carboxylates 5a,b or 6‐alkyl‐10‐chloro‐1‐oxo‐1,2,3,4,6,12‐hexahydroquinoxalino[2,3‐c]cinnolines 7a,b , respectively. Oxidation of compounds 5a,b with nitrous acid afforded the ethyl 1‐alkyl‐7‐chloro‐3‐ethoxycarbonylmethylene‐4‐hydroxy‐1,4‐dihydropyridazino‐[3,4‐b]quinoxaline‐4‐carboxylates 9a,b , whose reaction with base provided the ethyl 2‐(1‐alkyl‐7‐chloro‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxalin‐3‐yl)acetates 6a,b , respectively. On the other hand, oxidation of compounds 7a,b with N‐bromosuccinimide/water furnished the 4‐(1‐alkyl‐7‐chloro‐4‐oxo‐1,4‐dihydropyridazino[3,4‐b]quinoxalin‐3‐yl)butyric acids 8a,b , respectively. The reaction of compound 8a with hydroxylamine gave 4‐(7‐chloro‐4‐hydroxyimino‐1‐methyl‐1,4‐dihydropyridazino[3,4‐b]quinoxalin‐3‐yl)‐butyric acid 12 .     

Facile Synthesis of Novel 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one Derivatives as Potential Anticancer Agents

A series of 3‐(4‐phenylisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 6a – l ) derivatives has been efficiently synthesized by straightforward sequential reactions. Tandem Vilsmeier Hack reaction/cyclization/bromination/Suzuki cross‐coupling reactions were successfully applied to the preparation of title compounds in good‐to‐high yields. In the synthetic sequences, 3‐chloro‐3‐(2‐oxo‐2H‐chromen‐3‐yl)acrylaldehydes ( 2 ) were found to react with ammonium thiocyanate to yield the corresponding 3‐(isothiazol‐5‐yl)‐2H‐chromen‐2‐ones ( 3 ). These derivatives were brominated with N‐bromo succinamide to yield the corresponding regioselective 3‐(4‐bromoisothiazol‐5‐yl)‐2H‐chromen‐2‐one ( 4 ). Finally, compound 4 was treated with various phenyl/pyrazole/7H –pyrrolo[2,3‐d]pyrimidinyl boronic acids 5a – l in the presence of K₂CO₃ and Pd catalyst in dimethylformamide to yield the corresponding title derivatives 6a – l . All the synthesized compounds were characterized by analytical and spectral studies. All the final compounds were screened against different cancer cell lines (A549, PC3, SKOV3, and B16F10), and among these compounds, 6b , 6g , 6h , and 6l displayed moderate cytotoxic activity against the tested cell lines.     

Synthesis of 2‐Thioxohydropyridine‐3‐Carbonitrile, 2‐Alkylthiopyridine,Thienopyridine, Pyrazolopyridine Derivatives and Their Theoretical Calculations

Cyanothioacetamide ( 1 ) reacted with but‐2‐enal ( 2 ) to give the corresponding 4‐methyl‐2‐sulfanylpyridine‐3‐carbonitrile ( 7 ) which was used as a good starting material for the synthesis of 1‐(3‐amino‐4‐methylthieno[2,3‐b]pyridin‐2‐yl)ethan‐1‐one ( 10 ), 3‐amino‐4‐methylthieno[2,3‐b]pyridine‐2‐carboxamide ( 15 ), 3‐amino‐4‐methylthieno[2,3‐b]pyridine‐2‐carboxylate ( 18 ) and 3‐amino‐4‐methylthieno[2,3‐b]pyridin‐2‐ylarylketone 25a‐c through its reactions with each of (1‐chloroacetone ( 8 ), 3‐chloropentane‐2,4‐dione ( 11 ) or ethyl 2‐chloro‐3‐oxo‐butanoate ( 19 )), 2‐chloroacetamide ( 13 ), ethyl 2‐chloroacetate ( 16 ) and 2‐bromo‐1‐arylethan‐ 1 ‐one 23a‐c , respectively. Considering the data of elemental analyses, IR, ¹HNMR, mass spectra and theoretical calculations, structures of the newly synthesized heterocyclic compounds were elucidated.     

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.     

New diazadi(and tri)thia‐21‐crown‐7 ethers containing 8‐hydroxyquinoline side arms

A series of macrocyclic diazadi(and tri)thiacrown ethers containing two 5‐substituent‐8‐hydroxyquinoline side arms have been synthesized from the corresponding macrocyclic diazadi(and tri)thiacrown ethers. The crown ethers were obtained by reduction of the proper macrocyclic di(and tri)thiadiamides by borane‐tetrahydrofuran or by sodium borohydride‐boron trifluoride ethyl etherate‐tetrahydrofuran. The yields for the reduction of diamides by sodium borohydride‐boron trifluoride ethyl etherate‐tetrahydrofuran were higher than those by borane‐tetrahydrofuran. The following four methods were used to prepare macrocycles bearing two 8‐hydroxyquinoline side arms: (1) Mannich reaction with 8‐hydroxyquinoline; (2) Reductive animation with 8‐hydroxyquinoline‐2‐carboxaldehyde using sodium triacetoxyborohydride as the reducing agent; (3) Cyclization of N,N'‐bis(8‐hydroxyquinolin‐2‐ylmethyl)‐1,2‐bis(2‐aminoethoxy)ethane (38) with bis(α‐chloroamide) 5 ; and ( 4 ) A step‐by‐step process wherein macrocyclic trithiadiamide 11 was reduced by lithium aluminum hydride‐tetrahydrofuran to the cyclic monoamide 36 , which smoothly reacted with 5‐chloro‐8‐hydroxyquinoline to produce monosubstituted‐macrocyclic monoamide 39 .     

Cu (I) Catalyzed One Pot SN‐Click Reactions of Halogenated Coumarins and 1‐aza‐coumarins

A one pot three component, copper catalyzed azide‐alkyne cycloaddition reaction has been employed for the synthesis of bis‐coumarinyl triazoles ( A – D ) using 4‐chloro, 4‐bromomethyl, 3‐bromoacetyl and 4‐bromomethyl‐1‐aza‐coumarins ( I – IV ), sodium azide, and coumarin propargyl ethers ( V – IX ) in moderate yields.     

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.     

Synthesis and bioactivity of 6‐bromo‐2‐(substituted)‐3‐(1‐phenyl‐ethyl)‐ 3,4‐dihydro‐1H‐ isophosphinoline 2‐chalcogenides

Synthesis of 6‐bromo‐2‐(substituted)‐3‐(1‐phenyl‐ethyl)‐3,4‐dihydro‐1H‐isophosphinoline 2‐chalco‐genides derivatives (6) were synthesized from 2‐[(1‐phenylethylamino)methyl]‐4‐bromophenol ( 1 ) by reaction with aryl/alkyl phosphoro dichloridates ( 2 ) in the presence of triethylamine at 55°C to 60°C to obtained the title compounds ( 6a‐g ). The title compounds ( 6h‐j ), were prepared via intermediate route. Few other title compounds ( 8a‐c ) were accomplished through a two step synthetic route involving 1 with dichlorophenyl phosphine ( 2a ) and dichloroethyl phosphine ( 2a,b ) in the presence of triethylamine in dry toluene under N₂ atmosphere to form the corresponding trivalent phosphorus intermediate (7) . In the second step they were further converted to the corresponding chalcogenides 8a‐c by reaction with hydrogen peroxide, sulfur and selenium respectively. They exhibited significant antibacterial, fungal and insecticidal activity.     

7‐Halogenated 7‐Deazapurine 2′‐Deoxyribonucleosides Related to 2′‐Deoxyadenosine, 2′‐Deoxyxanthosine,and 2′‐Deoxyisoguanosine: Syntheses and Properties

A series of 7‐fluorinated 7‐deazapurine 2′‐deoxyribonucleosides related to 2′‐deoxyadenosine, 2′‐deoxyxanthosine, and 2′‐deoxyisoguanosine as well as intermediates 4b – 7b, 8, 9b, 10b , and 17b were synthesized. The 7‐fluoro substituent was introduced in 2,6‐dichloro‐7‐deaza‐9H‐purine ( 11a ) with Selectfluor (Scheme 1). Apart from 2,6‐dichloro‐7‐fluoro‐7‐deaza‐9H‐purine ( 11b ), the 7‐chloro compound 11c was formed as by‐product. The mixture 11b / 11c was used for the glycosylation reaction; the separation of the 7‐fluoro from the 7‐chloro compound was performed on the level of the unprotected nucleosides. Other halogen substituents were introduced with N‐halogenosuccinimides ( 11a → 11c – 11e ). Nucleobase‐anion glycosylation afforded the nucleoside intermediates 13a – 13e (Scheme 2). The 7‐fluoro‐ and the 7‐chloro‐7‐deaza‐2′‐deoxyxanthosines, 5b and 5c , respectively, were obtained from the corresponding MeO compounds 17b and 17c , or 18 (Scheme 6). The 2′‐deoxyisoguanosine derivative 4b was prepared from 2‐chloro‐7‐fluoro‐7‐deaza‐2′‐deoxyadenosine 6b via a photochemically induced nucleophilic displacement reaction (Scheme 5). The pK_a values of the halogenated nucleosides were determined (Table 3). ¹³C‐NMR Chemical‐shift dependencies of C(7), C(5), and C(8) were related to the electronegativity of the 7‐halogen substituents (Fig. 3). In aqueous solution, 7‐halogenated 2′‐deoxyribonucleosides show an approximately 70% S population (Fig. 2 and Table 1).     

Photochemical Reactions of N‐(2‐Halogenoalkanoyl) Derivatives of Anilines

The photochemical reactions of 2‐substituted N‐(2‐halogenoalkanoyl) derivatives 1 of anilines and 5 of cyclic amines are described. Under irradiation, 2‐bromo‐2‐methylpropananilides 1a – e undergo exclusively dehydrobromination to give N‐aryl‐2‐methylprop‐2‐enamides (=methacrylanilides) 3a – e (Scheme 1 and Table 1). On irradiation of N‐alkyl‐ and N‐phenyl‐substituted 2‐bromo‐2‐methylpropananilides 1f – m , cyclization products, i.e. 1,3‐dihydro‐2H‐indol‐2‐ones (=oxindoles) 2f – m and 3,4‐dihydroquinolin‐2(1H)‐ones (=dihydrocarbostyrils) 4f – m , are obtained, besides 3f – m . On the other hand, irradiation of N‐methyl‐substituted 2‐chloro‐2‐phenylacetanilides 1o – q and 2‐chloroacetanilide 1r gives oxindoles 2o – r as the sole product, but in low yields (Scheme 3 and Table 2). The photocyclization of the corresponding N‐phenyl derivatives 1s – v to oxindoles 2s – v proceeds smoothly. A plausible mechanism for the formation of the photoproducts is proposed (Scheme 4). Irradiation of N‐(2‐halogenoalkanoyl) derivatives of cyclic amines 5a – c yields the cyclization products, i.e. five‐membered lactams 6a , b , and/or dehydrohalogenation products 7a , c and their cyclization products 8a , c , depending on the ring size of the amines (Scheme 5 and Table 3).     

Triorganophosphine–dithiomonometaphosphoryl halides

The title compounds, ethyldiphenylphosphine–dithiomono­metaphosphoryl chloride, EtPh₂PPS₂Cl, C₁₄H₁₅ClP₂S₂, (I), and tris‐n‐propyl­phosphine–di­thio­monometa­phospho­ryl chloride and bromide, ⁿPr₃PPS₂Cl, C₉H₂₁ClP₂S₂, (II), and ⁿPr₃PPS₂Br, C₉H₂₁BrP₂S₂, (III), respectively, are the first phosphine‐stabilized di­thio­monometa­phospho­ryl halides to be structurally characterized. In the tris‐n‐propyl­phosphine derivatives, the central PP donor–acceptor bond becomes longer in the order bromo < chloro < fluoro. Substitution of the tris‐n‐propyl­phosphine group in (II) by the more bulky ethyl­di­phenyl­phosphine group also leads to a longer PP bond. These structural features agree with the observed ³¹P NMR data. In (II) and (III), the central P—P bond coincides with the crystallographic threefold axis, entailing site‐occupational disorder for the S₂Y group.     

Synthesis,In Vitro Biological Screening,and In Silico Computational Studies of Some Novel Imidazole‐2‐thiol Derivatives

Substituted imidazole analogues 2‐((5‐acetyl‐4‐methyl‐1‐phenyl‐1H‐imidazole‐2‐yl)thio)‐N‐phenylacetamides ( 3a – 3m ) have been synthesized from 1‐[1‐(phenyl)‐2‐mercapto‐4‐methyl‐1H‐imidazol‐5‐yl]‐ethanone ( 1a – 1e ) and 2‐chloro‐N‐phenylacetamide ( 2a – 2i ) in the presence of potassium carbonate as a catalyst in dimethylformamide under microwave irradiation as well as conventional method. Structures of the obtained compounds have been confirmed by advance spectroscopic techniques such as IR, ¹H NMR, ¹³C NMR, and mass spectrometry. All the synthesized compounds were tested for their in vitro antimicrobial and antituberculosis activities. Good antibacterial molecules were further screened for the bacterial resisted cell line, from which compound 3b shows maximum inhibition. In silico molecular docking study was carried out to discover the binding affinity of synthesized compounds with active site of transferase (PDB ID: 1HNJ) and antibiotic resistance (PDB ID: 1W3R) protein. Moreover, molecular dynamics study of the 3b ‐1W3R complex has also been performed, as 3b has a good antibacterial activity as compared with other.     

Synthesis and Antimicrobial Activity of Novel Iminophosphocin Derivatives

Iminophosphocins 8a – 8e and 9a – 9e were synthesized in four‐step reactions via Staudinger reaction. 3‐(Bromomethyl)‐1,2,3,4,5‐pentahydro‐3λ⁵‐naphtho[1,8‐f,g][1,5,3]diazaphosphocin‐3‐one ( 3 ) was prepared by reacting tris(bromomethyl)phosphineoxide ( 1 ) with 1,8‐diaminonaphthalene ( 2 ) in the presence of triethylamine (TEA) in dry tetrahydrofuran (THF), and treated with L‐valine methyl ester ( 4 ) and bis(2‐chloroethyl)amine ( 5 ) in the presence of TEA in dry THF to get 3‐methyl‐2‐[(3‐oxo‐1,2,3,4,5‐pentahydro‐3λ⁵‐naphtho[1,8‐f,g][1,5,3]diazaphosphocin‐3‐yl)methylamino]butanoate ( 6 ) and 3‐[di(2‐chloroethyl)aminomethyl]‐1,2,3,4,5‐pentahydro‐3λ⁵‐ naphtho[1,8‐f,g][1,5,3]diazaphosphocin‐3‐one ( 7 ). The compounds 6 and 7 were treated with trichlorosilane (SiCl₃H) in dry tetrahydrofuran (THF) to form the trivalent P(III) intermediates 8 and 9 , which were further treated with various alkyl azides in dry THF in 55–60°C to afford the title compounds 8a – 8e and 9a – 9e . Their structures were established by multi‐nuclear NMR and mass spectra. All the newly synthesized compounds were found to possess moderate anti‐microbial activity.     

Synthesis,Structure, and Photophysical Properties of the Di‐ and Trinuclear Phosphine‐Diimine Complexes of Copper(I)

Reactions of [Cu(NCMe)₄]⁺ with stoichiometric amount of diphosphine R₂P–(C₆H₄)_n–PR₂, (R = NC₄H₄, n = 1; R = Ph, n = 1, 2, 3) or tri‐phosphine 1, 3, 5‐(PPh₂–C₆H₄–)₃–C₆H₃ ligands give the corresponding di‐ or trinuclear copper(I) acetonitrile‐phosphine complexes 1 – 5 . Substitution of the labile acetonitrile groups with chelating aromatic diimines – 2, 2′‐bipyridine (bpy), 1, 10‐phenanthroline (phen), 5, 6‐dimethyl‐1, 10‐phenanthroline (dmp), 5, 6‐dibromo‐1, 10‐phenanthroline (phenBr₂) – gives the corresponding substituted compounds 6 – 16 . In all complexes 1 – 16 each central Cu^I atom has tetrahedral configuration completed with two N‐ and two P‐donor groups. The compounds obtained were characterized using elemental analysis, ESI‐MS, X‐ray crystallography, and NMR spectroscopy. All phosphine‐diimine compounds 6 – 16 are photoluminescent at room temperature both in dichloromethane solution and in solid state (λ_ex = 385 nm). In CH₂Cl₂ solution the maxima of emission bands are found in a range 540–640 nm, and in solid in a similar range 538–620 nm. Emission of 6 – 16 is assigned to the triplet excited state dominated by the charge transfer transitions with contribution of the MLCT character.     

Reactions of nitroarenes with secondary and tertiary carbanions bearing both a leaving group and electron‐withdrawing group: An approach to dihydronaphth[2,1‐c]isoxazole N‐oxides and dihydroisoxazolo[4,3‐f]quinoline N‐oxides

2‐Nitronaphthalene (1) and 6‐nitroquinoline (2) underwent direct cyclocondensation with secondary and tertiary carbanions derived from a methylene and methine group bearing both a leaving group and electron‐withdrawing group (e.g., methyl chloroacetate, ethyl chloroacetate, chloroacetonitrile, methyl 2‐chloropropionate, ethyl 2‐chloropropionate and 2‐chloropropionitrile) in the sodium hydride/N,N‐dimethylformamide system at low temperature, giving the corresponding dihydronaphth[2,1‐c]isoxazole N‐oxides 3 and dihy‐droisoxazolo[4,3‐f]quinoline N‐oxides 4 . On the other hand, nitroarenes 1 and 2 reacted with secondary carbanions in the sodium hydride/tetrahydrofuran system to yield the corresponding conventional vicarious nucleophilic substitution (VNS) products 5 and 6 .     

Synthesis and Anti‐proliferative Activity of Novel Polysubstitued Indazole Derivatives

A simple and efficient process is developed for the synthesis of new N‐(1‐alkyl‐3‐chloro‐4‐ethoxy‐1H‐indazol‐5‐yl)‐arylsulfonamides 4a – d and N‐(1‐alkyl‐3‐chloro‐1H‐indazol‐5‐yl)‐arylsulfonamides 5a – d through the reduction of 1‐alkyl‐3‐chloro‐5‐nitroindazoles 2a , b with SnCl₂ in ethanol followed by coupling the corresponding amine with arylsulfonyl chlorides in pyridine. All the newly synthesized compounds have been characterized by elemental analysis and spectroscopic data. Some compounds were tested for their in vitro antiproliferative activities against two selected human cancer cell lines A2780 and A549. Among all of these derivatives, compound 5d showed the most potent antiproliferative activity against A2780 (IC₅₀ = 5.47 ± 1.45 μM) and A549 (IC₅₀ = 7.73 ± 1.66 μM) cell lines.