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 of 5‐(6‐Pyridazinone‐3‐yl)‐2‐Glycosylamino‐1,3,4‐Oxadiazoles

N‐Glycosyl‐2‐(1,4,5,6‐tetrahydropyridazin‐6‐one‐3‐carbonyl)‐hydrazinecarbothioamides 3a‐3g and N‐glycosyl‐2‐(1,6‐dihydropyridazin‐6‐one‐3‐carbonyl)‐hydrazinecarbothioamides 5a‐5g were prepared by the reaction of glycosyl isothiocyanates with the compounds 1,4,5,6‐tetrahydro‐3‐hydrozinecarbonyl‐6‐pyridazinone ( 1 ) and 1,6‐dihydro‐3‐hydrozinecarbonyl‐6‐pyridazinone ( 2 ). The terminal heterocyclic compounds 1,3,4‐oxadiazole derivatives were obtained from cyclization of compounds ( 3a‐3g ) and ( 5a‐5g ) by mercuric acetate. Their structures were confirmed by IR, ¹H NMR, MS and elemental analyses.     

Investigation of Some Functionalization Reactions of 4‐Benzoyl‐5‐phenyl‐1‐(4‐methoxyphenyl)‐1H‐pyrazole‐3‐carbonyl Chloride and Their Antimicrobial Activity

The 1H‐pyrazole‐3‐carboxylic acid 1 was converted via reactions of its acid chloride 3 with various asymmetrical disubstituted urea and alcohol derivatives into the corresponding novel 4‐benzoyl‐N‐(N′,N′‐dialkylcarbamyl)‐1‐(4‐methoxyphenyl)‐5‐phenyl‐1H‐pyrazole‐3‐carboxamide 4a , b and alkyl 4‐benzoyl‐1‐(4‐methoxyphenyl)‐5‐phenyl‐1H‐pyrazole‐3‐carboxylate 7a‐c , respectively, in good yields (57%‐78%). Friedel‐Crafts reactions of 3 with aromatic compouns for 15 min.‐2 h led to the formation of the 4‐3‐diaroyl‐1‐(4‐hydroxyphenyl)‐5‐phenyl‐1H‐pyrazoles 9a‐c , 4‐benzoyl‐1‐(4‐methoxyphenyl)‐3‐aroyl‐5‐phenyl‐1H‐pyrazoles 10a , b and than from the acylation reactions of 9a‐c were obtained the 3,4‐diaroyl‐1‐(4‐acyloxyphenyl)‐5‐phenyl‐1H‐pyrazoles 13a‐d . The structures of all new synthesized compounds were established by NMR experiments such as ¹H, and ¹³C, as well as 2D COSY and IR spectroscopic data, and elemental analyses. All the compounds were evaluated for their antimicrobial activities (agar diffusion method) against eight bacteria and two yeasts.     

Heterobimetallische Komplexe von Lithium,Aluminium und Gold mit dem N‐[2‐N′,N′‐(Dimethylaminoethyl)‐N‐methyl‐aminoethyl]‐ferrocenyl‐Liganden (η5‐C5H5)Fe{η5‐C5H3[CH(CH3)N(CH3)CH2CH2NMe2]‐2}

Heterobimetallic Complexes of Lithium, Aluminum, and Gold with the N ‐[2‐ N ′, N ′‐(dimethylaminoethyl)‐ N ‐methyl‐aminoethyl]‐ferrocenyl Ligand (η⁵‐C₅H₅)Fe{η⁵‐C₅H₃[CH(CH₃)N(CH₃)CH₂CH₂NMe₂]‐2} N‐[2‐N′,N′‐(dimethylaminoethyl)‐N‐methyl‐aminoethyl]ferrocene FcN,NH ( 1 ) reacts with ⁿBuLi under formation of the lithium organyl (FcN,N)Li ( 2 ). At reactions of 2 with AlBr₃ and AuCl · PPh₃ the heterobimetallic organo derivatives (FcN,N)AlBr₂ ( 3 ), (FcN,N)Au · PPh₃ ( 4 ) are formed. A detailed characterization of 2 – 4 was carried out by single crystal x‐ray analyses as well as by NMR and Mößbauer spectroscopy.     

Kinetics and mechanism of gas‐phase pyrolysis of N‐aryl‐3‐oxobutanamide ketoanilides,their 2‐arylhydrazono derivatives,and related compounds

Rates and products of reaction and Arrhenius activation parameters were determined for the gas‐phase thermolysis of 14 substrates of the title compounds using sealed pyrex reactor tubes and HPLC/UV‐VIS to monitor substrate pyrolysis. The 14 compounds under study are N‐phenyl‐3‐oxo‐ ( 1 ), N‐(p‐chlorophenyl)‐3‐oxo‐ ( 2 ), N‐(p‐methylphenyl)‐3‐oxo‐ ( 3 ), and N‐(p‐methoxyphenyl)‐3‐oxobutanamide ( 4 ), in addition to (i) four substrates ( 5–8 ) obtained by the replacement of the pairs of methylene hydrogens at the 2‐position of compounds ( 1–4 ), each pair by a phenylhydrazono group; (ii) three arylhydrazono derivatives ( 9–11 ) in which Cl, CH₃, or OCH₃ groups are substituted at the para position of the phenylhydrazono moiety of compound 5 ; (iii) 3‐oxobutanamide (acetoacetamide, 12 ), N‐phenyl‐3‐oxo‐3‐phenylpropanamide ( 13 ), and N,N′‐diphenylpropanediamide ( 14 ). The reactions were conducted over 374–546 K temperature range, and the values of the Arrhenius log A(s^?1) and E_a(kJ mol^?1) of these reactions were, respectively, 12.0 ± 2.0 and 119.2 ± 17.0 for the ketoanilides ( 1–4, 12–14 ), and 13.0 ± 0.7 and 157.5 ± 8.6 for the arylhyrazono compounds ( 5–11 ). Kinetically, the arylhydrazono derivatives were found to be ca. 1.4 × 10³ to 5.7 × 10³ times less reactive than the parent ketoanilides. A mechanism is proposed to account for reaction products and to rationalize molecular reactivities. © 2006 Wiley Periodicals, Inc. Int J Chem Kinet 39: 82–91, 2007     

Sequential C−H Borylation and N‐Demethylation of 1,1′‐Biphenylamines: Alternative Route to Polycyclic BN‐Heteroarenes

Described herein is an unprecedented access to BN‐polyaromatic compounds from 1,1′‐biphenylamines by sequential borane‐mediated C(sp²)?H borylation and intramolecular N‐demethylation. The conveniently in situ generated Piers’ borane from a borinic acid reacts with a series of N,N‐dimethyl‐1,1′‐biphenyl‐2‐amines in the presence of PhSiH₃ to afford six‐membered amine‐borane adducts bearing a C(sp²)?B bond at the C2′‐position. These species undergo an intramolecular N‐demethylation with a B(C₆F₅)₃ catalyst to provide BN‐isosteres of polyaromatics. According to computational studies, a stepwise ionic pathway is suggested. Photophysical characters of the resultant BN‐heteroarenes shown them to be distinctive from those of all‐carbon analogues.     

Synthesis and pharmacological properties of N‐substituted‐N′‐(4,6‐dimethylpyrimidin‐2‐yl)‐thiourea derivatives and related fused heterocyclic compounds

A series of new N‐Substituted‐N′‐(4,6‐dimethylpyrimidin‐2‐yl)‐thiourea derivatives ( 3a , 3b , 3c , 3d ) and related fused heterocyclic compounds ( 4a , 4b , 4c , 4d ) were synthesized using tetrabutylammonium bromide as phase transfer catalyst (PTC). N‐[(2E)‐5,7‐dimethyl‐2H‐[1,2,4] thiadiazolo [2,3‐a] pyrimidin‐2‐ylidene] derivatives ( 4a , 4b , 4c , 4d ) were prepared by oxidative cyclization of 3a , 3b , 3c , 3d . The structures of these novel compounds were characterized by IR, ¹H NMR, ¹³C NMR, mass spectrometry, and the elemental analysis. The crystal structures were determined from single crystal X‐ray diffraction data. The results indicated that the compounds possessed a broad spectrum of activity against the tested microorganisms and showed higher activity against fungi than bacteria. Compounds 3d and 3a exhibited the greatest antimicrobial activity. J. Heterocyclic Chem., 2011.     

Synthesis of Novel 3‐Acetyl‐2‐Aryl‐5‐(3‐Aryl‐1‐Phenyl‐Pyrazol‐4‐yl)‐2,3‐Dihydro‐1,3,4‐Oxadiazoles

A series of novel pyrazolyl‐substituted 1,3,4‐oxadiazole derivatives ( 4a‐4o ) were prepared by cyclization of the intermediate N′‐((3‐aryl‐l‐phenyl‐pyrazol‐4‐yl)methylene)arylhydrazide with acetic anhydride. The structures of the new compounds were confirmed by IR, ¹H NMR, MS and elemental analysis. Furthermore, preliminary bioassay of some of the title compounds indicated that they exhibited moderate inhibition against HIV‐1 PR.     

Synthesis of Some N-Alkoxycarbonyl-N″-benzoyl-benzamidrazones（p-toluamidrazones） and 1,3,5-Trisubstituted 1,2,4-Triazole Derivatives from N-Benzoylimidates and their Antimicrobial and Anticancer Screening Studies

Some new N-alkoxycarbonyl-N″-benzoyl-benzamidrazones （p-toluamidrazones） 3a-3d, and 1,3,5-trisubstituted 1,2,4-triazole 4a-4h derivatives by starting from N-benzoylbenzimidates or N-benzoyl-p-toluimidates. The structures of compounds 3 and 4 were established on the basis of elemental analyses, IR, ^1H NMR, ^13C NMR and UV data. Antimicrobial experiments of the compounds performed by using agar-well diffusion and broth microdilution methods revealed that only compounds 3a-3d, 4a and 4b showed inhibitory effect only on Candida albicans ATCC 60193. However, compound 4b had also specific antibacterial activity against Staphylococcus aureus ATCC 25923. The other compounds showed neither antifungal nor antibacterial activities. Compounds 3a, 4a and 4b have been screened on three human tumor cell lines, breast cancer （MCF7）, non small cell lung cancer （NCI-H460）, and CNS cancer （SF-268） at the National Cancer Institute （NCI）, USA, which were found to exhibit low antiproliferative activity.     

Preparation,Structural Characterization,and Antifungal Activities of Complexes of Group 12 Metals with 2‐Acetylpyridine‐ and 2‐Acetylpyridine‐N‐oxide‐4N‐phenylthiosemicarbazones

Reaction of group 12 metal dihalides in ethanolic media with 2‐acetylpyridine ⁴N‐phenylthiosemicarbazone ( H4PL ) and 2‐acetylpyridine‐N‐oxide ⁴N‐phenylthiosemicarbazone ( H4PLO ) afforded the compounds [M(H4PL)X₂] (X = Cl, Br, M = Zn, Cd, Hg; X = I, M = Zn, Cd) ( 1–8 ), [Hg(4PL)I]₂ ( 9 ) and [M(H4PLO)X₂] (X = Cl, Br, I, M = Zn, Cd, Hg) ( 10–18 ). H4PL , H4PLO and their complexes were characterized by elemental analysis and by IR and ¹H and ¹³C NMR spectroscopy (and the cadmium complexes by ¹¹³Cd NMR spectroscopy), and H4PL , H4PLO , ( 5 · DMSO) and ( 9 ) were additionally studied by X‐ray diffraction. H4PL is N,N,S‐tridentate in all its complexes, including 9 , in which it is deprotonated, and H4PLO is in all cases O,N,S‐tridentate. In all the complexes, the metal atoms are pentacoordinate and the coordination polyhedra are redistorted tetragonal pyramids. In assays of antifungal activity against Aspergillus niger and Paecilomyces variotii, the only compound to show any activity was [Hg(H4PLO)I₂] ( 18 ).     

Synthetic approaches to 3‐substituted‐5′‐(N‐pyridiniummethyl)‐4′,5′‐dihydropsoralen

New synthetic approaches to 3‐substituted‐5′‐(N‐pyridiniummethyl)‐4′,5′‐dihydropsoralens are described. The novel pathways presented utilize appropriately substituted coumarins and 4′,5′‐dihydropsoralens. The compounds proposed represent potential therapeutic agents for psoralen uv radiation treatment.     

The reaction of 3,4‐diamino‐1,2,5‐oxadiazoles with formaldehyde

The compounds 5,6‐dihydro‐4H‐imidazo[4,5‐c][1,2,5]oxadiazole ( 3a , R?H), 4,6,10,12‐tetramethyl‐5,6,11,12‐tetrahydro‐4H,10H‐bis(1,2,5)oxadiazolo[3,4‐d:3′,4′‐I][1,3,6,8]tetraazecine ( 4b , R?CH₃), N³,N³′‐methylenebis‐3,4‐diamino‐1,2,5‐oxadiazole ( 5a , R?H) and N³,N³′‐methylenebis(N,N′‐dimethyl‐3,4‐diamino‐1,2,5‐oxadiazolee) ( 5b , R?CH₃) were synthesized from the reaction of formaldehyde with 3,4‐diamino‐1,2,5‐oxadiazole and N,N′‐3,4‐dimethylamino‐1,2,5‐oxadiazole in an acetonitrile.     

Exploring the Effect of Bioisosteric Replacement of Carboxamide by a Sulfonamide Moiety on N‐Glycosidic Torsions and Molecular Assembly: Synthesis and X‐ray Crystallographic Investigation of N‐(β‐D‐Glycosyl)sulfonamides as N‐Glycoprotein Linkage Region Analogues

N‐Glycoprotein linkage region constituents, 2‐acetamido‐2‐deoxy‐β‐D ‐glucopyranose (GlcNAc) and asparagine (Asn) are conserved among all the eukaryotes. To gain a better understanding for nature’s choice of GlcNAcβAsn as linkage region constituents and inter‐ and intramolecular carbohydrate–protein interactions, a detailed systemic structural study of the linkage region conformation is essential. Earlier crystallographic studies of several N‐(β‐glycopyranosyl)alkanamides showed that N‐glycosidic torsion, ?_N, is influenced to a larger extent by structural variation in the sugar part than that of the aglycon moiety. To explore the effect of the bioisosteric replacement of a carboxamide group by a sulfonamide moiety on the N‐glycosidic torsions as well as on molecular assembly, several glycosyl methanesulfonamides and glycosyl chloromethanesulfonamides were synthesized as analogues of the N‐glycoprotein linkage region, and crystal structures of seven of these compounds have been solved. A comparative analysis of this series of crystal structures as well as with those of the corresponding alkanamido derivatives revealed that N‐glycosidic torsion, ?_N, does not alter significantly. Methanesulfonamido and chloromethanesulfonamido derivatives of GlcNAc display a different aglycon conformation compared to other sulfonamido analogues. This may be due to the cumulative effect of the direct hydrogen bonding between N1 and O1′ and C? H???O interactions of the aglycon chain, revealing the uniqueness of the GlcNAc as the linkage sugar.     

Synthesis and biological activity of novel N‐benzoyl‐N‐tert‐butyl‐N′‐(β‐triphenylgermyl)propionylhydrazines

A series of new N‐benzoyl‐N‐tert‐butyl‐N′‐(β‐triphenylgermyl)propionylhydrazines were synthesized by the condensation reaction of β‐triphenylgermyl propanoic acid with N‐benzoyl‐N‐tert‐butylhydrazines in good yields by using N,N′‐dicyclohexylcorbodiimide as dehydrating agent. These title compounds were evaluated for molting hormone mimicking activity. The results of bioassay showed that the compounds exhibit moderate larvicidal activity, and toxicity assays indicated that the title compounds can induce a premature, abnormal and lethal larval molt. We found that the title compounds possess potential anticancer activities in vitro. Copyright © 2002 John Wiley & Sons, Ltd.     

Synthesis and Antioxidant Activities of Novel 4,4′‐Arylmethylene‐bis(1H‐pyrazole‐5‐ol)s from Lignin

A series of novel bispyrazoles joined by arylmethylene at C‐4 position were synthesized with aromatic aldehydes obtained from lignin and screened for their in vitro antioxidant activities by N,N‐diphenyl‐N′‐picrylhydrazyl (DPPH) and 2,2′‐azino‐bis(3‐ethylenzothiazoline‐sulphonic acid) diammonium salt (ABTS⁺) radical scavenging assays. All of these compounds exhibited good DPPH and ABST⁺ radical scavenging activities as compared to the standard, Trolox, which suggested their potential as promising agents for curing tumors or other free radical‐related diseases.     

Structure and spectroscopic properties of the dimeric copper(I) N‐heterocyclic carbene complex [Cu2(CNCt‐Bu)2](PF6)2

In recent years, the use of copper N‐heterocyclic carbene (NHC) complexes has expanded to fields besides catalysis, namely medicinal chemistry and luminescence applications. In the latter case, multinuclear copper NHC compounds have attracted interest, however, the number of these complexes in the literature is still quite limited. Bis[μ‐1,3‐bis(3‐tert‐butylimidazolin‐2‐yliden‐1‐yl)pyridine]‐1κ⁴C²,N:N,C^2′;2κ⁴C²,N:N,C^2′‐dicopper(I) bis(hexafluoridophosphate), [Cu₂(C₁₉H₂₅N₅)₂](PF₆)₂, is a dimeric copper(I) complex bridged by two CNC, i.e. bis(N‐heterocyclic carbene)pyridine, ligands. Each Cu^I atom is almost linearly coordinated by two NHC ligands and interactions are observed between the pyridine N atoms and the metal centres, while no cuprophilic interactions were observed. Very strong absorption bands are evident in the UV–Vis spectrum at 236 and 274 nm, and an emission band is observed at 450 nm. The reported complex is a new example of a multinuclear copper NHC complex and a member of a compound class which has only rarely been reported.     

Synthese,Komplexbildung und Kristallstrukturen von Cyclotriphosphazenen mit N,N,N′,N′‐Tetramethylguanidingruppen

Synthesis, Complex Formation, and Crystal Structures of Cyclotriphosphazenes with N,N,N′,N′‐Tetramethylguanidine Groups The reactions of monochloropentaphenoxycyclotriphosphazene and hexachlorocyclotriphosphazene with N,N,N′,N′‐tetramethylguanidine yield the mono and tetra substituted products 2‐(N,N,N′,N′‐tetramethylguanidine)‐2,4,4,6,6‐pentaphenoxy‐2 λ⁵,4 λ⁵,6 λ⁵‐cyclotriphosphaza‐1,3,5‐trien ( 1 ) and 2,2‐dichlor‐4,4,6,6‐tetra‐(N,N,N′,N′‐tetramethylguanidine‐2 λ⁵,4 λ⁵,6 λ⁵‐cyclotriphosphaza‐1,3,5‐trien ( 2 ) respectively; no hexa functionalized product could be obtained, even with high excess of the nucleophile. Electron release from the exocyclic amino substituent reduces the acceptor ability of the phosphorus atoms. Reactions of ( 2 ) with copper(II) chloride and palladium(II) bis(acetonitrilo)dichloride yield metal complexes with a ligand : metal ratio of 1 : 2. The X‐ray structure analyses of N₃P₃Cl₂(NC(N(CH₃)₂)₂)₄ · 2 CuCl₂ ( 2 a ) and N₃P₃Cl₂(NC(N(CH₃)₂)₂)₄ · 2 PdCl₂ ( 2 b ) show that each metal atom is coordinated by two imino nitrogen atoms in geminal positions and two chloride atoms in a square planar arrangement.     

Synthesis and Spectroscopic Study of Some New Phosphoramidates,Crystal Structures of N‐Benzoyl‐N′,N″‐bis(azetidinyl)phosphoric Triamide and N‐Benzoyl‐N′,N″‐bis(hexamethylenyl)phosphoric Triamide

Some new N‐carbonyl, phosphoramidates with formula C₆H₅C(O)N(H)P(O)R₂ (R = NC₃H₆ ( 1 ), NC₆H₁₂ ( 2 ), NHCH₂CH=CH₂ ( 3 ), N(C₃H₇)₂ ( 4 )) and CCl₃C(O)N(H)P(O)R′₂ (R′ = NC₃H₆ ( 5 ), NHCH₂CH=CH₂ ( 6 )) were synthesized and characterized by ¹H, ¹³C, ³¹P NMR and IR spectroscopy and elemental analysis. The structures were determined for compounds 1 and 2 . Compound 1 exists as two crystallographically independent molecules in crystal lattice. Both compounds 1 and 2 produced dimeric aggregates via intermolecular ‐P=O…H‐N‐ hydrogen bonds, which in compound 2 is a centrosymmetric dimer. In compounds with four‐membered ring amine groups, ³J(P,C)>²J(P,C), in agreement with our previous studies about five‐membered ring amine groups. Also, ³J(P,C) values in compounds 1 and 5 are greater than in compounds with five‐, six‐ and seven‐membered ring amine groups.     

Synthesis and Characterization of New Thebaine Derivatives as Potential Opioid Agonists and Antagonists: 2‐[N‐(1H‐Tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazoles

In this study, we report the synthesis a series of novel 2‐[N‐(1H‐tetrazol‐5‐yl)‐6,14‐endo‐etheno‐6,7,8,14‐tetrahydrothebaine‐7α‐yl]‐5‐phenyl‐1,3,4‐oxadiazole derivatives ( 7a – e ) which have potential opioid antagonist and agonist. The substitution reaction of 6,14‐endo‐ethenotetrahydrothebaine‐7α‐carbohydrazide with corresponding benzoyl chlorides gave diacylhydrazine compounds 4a – e in good yields. The treatment of compounds 4a – e with POCl₃ caused the conversion of side‐chain of compounds 5a – e into 1,3,4‐oxadiazole ring at C(7) position; thus, compounds 5a – e were obtained. Subsequently, cyanamides ( 6a – e ) were prepared from compounds 5a – e and then compounds 7a – e were synthesized by the azidation of 6a – e with NaN₃. The structures of the compounds were established on the basis of their IR, ¹H NMR, ¹³C APT, 2D‐NMR (COSY, NOESY, HMQC, HMBC) and high‐resolution mass spectral data.     

Five N′‐benzylidene‐N‐methylpyrazine‐2‐carbohydrazides

The compounds N′‐benzylidene‐N‐methylpyrazine‐2‐carbohydrazide, C₁₃H₁₂N₄O, (IIa), N′‐(2‐methoxybenzylidene)‐N‐methylpyrazine‐2‐carbohydrazide, C₁₄H₁₄N₄O₂, (IIb), N′‐(4‐cyanobenzylidene)‐N‐methylpyrazine‐2‐carbohydrazide dihydrate, C₁₄H₁₁N₅O·2H₂O, (IIc), N‐methyl‐N′‐(2‐nitrobenzylidene)pyrazine‐2‐carbohydrazide, C₁₃H₁₁N₅O₃, (IId), and N‐methyl‐N′‐(4‐nitrobenzylidene)pyrazine‐2‐carbohydrazide, C₁₃H₁₁N₅O₃, (IIe), have dihedral angles between the pyrazine rings and the benzene rings in the range 55–78°. These methylated pyrazine‐2‐carbohydrazides have supramolecular structures which are formed by weak C—H...O/N hydrogen bonds, with the exception of (IIc) which is hydrated. There are π–π stacking interactions in all five compounds. Three of these structures are compared with their nonmethylated counterparts, which have dihedral angles between the pyrazine rings and the benzene rings in the range 0–6°.