Green Synthesis of 1‐(1,2,4‐Triazol‐4‐yl)spiro[azetidine‐2,3′‐(3H)indole]‐2′,4′(1′H)‐diones as Potential Insecticidal Agents

One pot green synthesis of 1‐(1,2,4‐triazol‐4‐yl)spiro[azetidine‐2,3′‐(3H)‐indole]‐2′,4′(1′H)‐diones was carried out by the reaction of indole‐2,3‐diones,4‐amino‐4H‐1,2,4‐triazole and acetyl chloride/chloroacetyl chloride in ionic liquid [bmim]PF₆ with/without using a catalyst. It was also prepared by conventional method via Schiff's bases, 3‐[4H‐1,2,4‐triazol‐4‐yl]imino‐indol‐2‐one. Further, the corresponding phenoxy derivatives were obtained by the reaction of chloro group attached to azetidine ring with phenols. The synthesized compounds were characterized by analytical and spectral (IR, ¹H NMR, ¹³C NMR, and FAB mass) data. Evaluation for insecticidal activity against Periplaneta americana exhibited promising results.     

5‐(1,2,3‐Triazol‐1‐yl)tetrazole Derivatives of an Azidotetrazole via Click Chemistry

N? C bonded (non‐bridged) 5‐(1,2,3‐triazol‐1‐yl)tetrazoles were synthesized by the Cu^I‐catalyzed 1,3‐dipolar azide–alkyne cycloaddition click reaction using 5‐azido‐N‐(propan‐2‐ylidene)‐1H‐tetrazole ( 1 ). For example, the click reaction of 1 in the presence of CuSO₄?5 H₂O and Na ascorbate at 65–70 °C for 48 h in CH₃CN/H₂O co‐solvent was found to be limited to only terminal alkynes that have electron‐withdrawing groups, CF₃C?CH ( 2 a ) and SF₅C?CH ( 2 b ), giving rise to isopropylidene‐[5‐(4‐trifluoromethyl‐1,2,3‐triazol‐1‐yl)tetrazol‐1‐yl]amine ( 3 a ) and isopropylidene‐[5‐(4‐pentafluorosulfanyl‐1,2,3‐triazol‐1‐yl)tetrazol‐1‐yl]amine ( 3 b ) in 47 % and 66 % yields, respectively. When carried out under conditions using CuI and 2,6‐lutidine as catalysts at 0 °C for 13 h in CHCl₃, the click reaction was versatile toward alkynes even those having electron‐donating groups. Properties of new products were determined and compared with those of 1 . Heats of formation, detonation pressures, detonation velocities and impact sensitivities are reported for these new 5‐(1,2,3‐triazol‐1‐yl)tetrazoles.     

Stereoselective synthesis and biological activities of O‐(E)‐1‐{1‐[(6‐chloropyridin‐3‐yl)methyl]‐5‐methyl‐1H‐1,2,3‐triazol‐4‐yl}ethyleneamino‐O‐ethyl‐O‐arylphosphorothioates

To find novel lead compounds having high insecticidal activity, a series of phosphorothioate derivatives containing 1,2,3‐triazole and pyridine rings were synthesized by the reaction of 1‐{1‐[(6‐chloropyridin‐3‐yl)methyl]‐5‐methyl‐1H‐1,2,3‐triazol‐4‐yl}ethanone oxime with phosphorochloridothioates. Their structures were confirmed by IR, ¹H NMR, ³¹P NMR, mass spectrometry, and elemental analyses. The structure of 6c was determined by single crystal X‐ray diffraction, which is thermodynamically stable E isomer. The results of preliminary bioassay indicate that some title compounds possess insecticidal activity to some extent. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:15–20, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20367     

Expanding the Scope of 2′‐SCF3 Modified RNA

The 2′‐trifluoromethylthio (2′‐SCF₃) modification endows ribonucleic acids with exceptional properties and has attracted considerable interest as a reporter group for NMR spectroscopic applications. However, only modified pyrimidine nucleosides have been generated so far. Here, the syntheses of 2′‐SCF₃ adenosine and guanosine phosphoramidites of which the latter was obtained in highly efficient manner by an unconventional Boc‐protecting group strategy, are reported. RNA solid‐phase synthesis provided site‐specifically 2′‐SCF₃‐modified oligoribonucleotides that were investigated intensively. Their excellent behavior in ¹⁹F NMR spectroscopic probing of RNA ligand binding was exemplified for a noncovalent small molecule–RNA interaction. Moreover, comparably to the 2′‐SCF₃ pyrimidine nucleosides, the purine counterparts were also found to cause a significant thermodynamic destabilization when located in double helical regions. This property was considered beneficial for siRNA design under the aspect to minimize off‐target effects and their performance in silencing of the BASP1 gene was demonstrated.     

Efficient Access to Peptidyl‐RNA Conjugates for Picomolar Inhibition of Non‐ribosomal FemXWv Aminoacyl Transferase

Peptidyl–RNA conjugates have various applications in studying the ribosome and enzymes participating in tRNA‐dependent pathways such as Fem transferases in peptidoglycan synthesis. Herein a convergent synthesis of peptidyl–RNAs based on Huisgen–Sharpless cycloaddition for the final ligation step is developed. Azides and alkynes are introduced into tRNA and UDP‐MurNAc‐pentapeptide, respectively. Synthesis of 2′‐azido RNA helix starts from 2′‐azido‐2′‐deoxyadenosine that is coupled to deoxycytidine by phosphoramidite chemistry. The resulting dinucleotide is deprotected and ligated to a 22‐nt RNA helix mimicking the acceptor arm of Ala‐tRNA^Ala by T4 RNA ligase. For alkyne UDP‐MurNAc‐pentapeptide, meso‐cystine is enzymatically incorporated into the peptidoglycan precursor and reduced, and L ‐Cys is converted to dehydroalanine with O‐(mesitylenesulfonyl)hydroxylamine. Reaction of but‐3‐yne‐1‐thiol with dehydroalanine affords the alkyne‐containing UDP‐MurNAc‐pentapeptide. The Cu^I‐catalyzed azide alkyne cycloaddition reaction in the presence of tris[(1‐hydroxypropyl‐1H‐1,2,3‐triazol‐4‐yl)methyl]amine provided the peptidyl‐RNA conjugate, which was tested as an inhibitor of non‐ribosomal FemX_Wv aminoacyl transferase. The bi‐substrate analogue was found to inhibit FemX_Wv with an IC₅₀ of (89±9) pM , as both moieties of the peptidyl–RNA conjugate contribute to high‐affinity binding.     

Diamine‐Catalyzed Addition of ZnEt2 to PhC(O)CF3: Two Mechanisms and Autocatalytic Asymmetric Enhancement

NMR spectroscopic studies of the catalytic addition reaction of ZnEt₂ to PhC(O)CF₃ in the presence of three very efficient catalysts [TMEDA, tBuBOX, and L ; where L is a chiral diamine synthesized from optically pure (R,R)‐1,2‐diphenylethylenediamine and (S)‐2,2′‐bis‐(bromomethyl)‐1,1′‐binaphthalene] reveal large differences in their behavior. For the ligands TMEDA and tBuBOX, the catalysis shows no unusual features and proceeds via [(N?N)Zn(Et){OC(CF₃)(Et)Ph}]. For N?N? L , the observation of autocatalytic asymmetric enhancement during the catalysis, and unusual inverse concentration dependence on the reaction rate, indicate the participation of an additional novel catalytic cycle that goes through a dinuclear intermediate containing one ZnEt₂ and one ZnEt fragment connected by N?N and OR bridges. Interestingly, the ¹⁹F NMR signals of the main product of the reaction ([Zn(Et){OC*(CF₃)(Et)Ph}]₂) allowed us to assess the enantioselectivity of the processes in situ without the assistance of chiral chromatography.     

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.     

Design,Synthesis, and Characterization of (2‐Alkyl/aryl‐3H‐imidazo[2,1‐c][1,2,4]triazol‐3‐yl)(aryl)methanone

The important therapeutic properties of imidazole‐related drugs have encouraged the medicinal chemists to synthesize and test a large number of novel molecules. In this investigation, it was of interest to synthesize (2‐alkyl/aryl‐3H‐imidazo[2,1‐c][1,2,4]triazol‐3‐yl)(aryl)methanone by short reaction times of N‐triazol‐3‐yl imidate with phenacyl bromides under basic conditions. All compounds were elucidated by spectroscopic methods including IR, ¹H‐NMR, ¹³C‐NMR, elemental analyses, and mass spectral analysis.     

Synthesis,structure, and biological activity of novel 4,5‐disubstituted thiazolyl urea derivatives

Novel 1‐(2,4‐dichlorophenyl)‐3‐[4‐aryl‐5‐(1H‐1,2,4‐triazol‐1‐yl)thiazol‐2‐yl] urea derivatives were synthesized by the reaction of 2‐amino‐4‐sustituted phentyl‐5‐(1H‐1,2,4‐triazol‐1‐yl) thiazoles with 2,4‐dichloro‐1‐isocyanatobenzene. Structures of the title compounds were confirmed by the elemental analysis, ¹H NMR, and single crystal X‐ray diffraction analysis. Biological evaluation showed that some of them possess promising antitumor activities. © 2008 Wiley Periodicals, Inc. Heteroatom Chem 19:2–6, 2008; Published online in Wiley InterScience ( www.interscience.wiley.com ). DOI 10.1002/hc.20375     

In‐ and Out‐of‐Cavity Interactions by Modulating the Size of Ruthenium Metallarectangles

Cationic (arene)ruthenium‐based tetranuclear complexes of the general formula [Ru₄(η⁶‐p‐cymene)₄(μ‐N∩N)₂(μ‐OO∩OO)₂]⁴⁺ were obtained from the dinuclear (arene)ruthenium complexes [Ru₂(η⁶‐p‐cymene)₂(μ‐OO∩OO)₂Cl₂] (p‐cymene=1‐methyl‐4‐(1‐methylethyl)benzene, OO∩OO=5,8‐dihydroxy‐1,4‐naphthoquinonato(2?), 9,10‐dihydroxy‐1,4‐anthraquinonato(2?), or 6,11‐dihydroxynaphthacene‐5,12‐dionato(2?)) by reaction with pyrazine or bipyridine linkers (N∩N=pyrazine, 4,4′‐bipyridine, 4,4′‐[(1E)‐ethene‐1,2‐diyl]bis[pyridine]) in the presence of silver trifluoromethanesulfonate (CF₃SO₃Ag) (Scheme). All complexes 4 – 12 were isolated in good yield as CF₃SO salts, and characterized by NMR and IR spectroscopy. The host–guest properties of the metallarectangles incorporating 4,4′‐bipyridine and (4,4′‐[(1E)‐ethene‐1,2‐diyl]bis[pyridine] linkers were studied in solution by means of multiple NMR experiments (1D, ROESY, and DOSY). The largest metallarectangles 10 – 12 incorporating (4,4′‐[(1E)‐ethene‐1,2‐diyl]bis[pyridine] linkers are able to host an anthracene, pyrene, perylene, or coronene molecule in their cavity, while the medium‐size metallarectangles 7 – 9 incorporating 4,4′‐bipyridine linkers are only able to encapsulate anthracene. However, out‐of‐cavity interactions are observed between these 4,4′‐bipyridine‐containing rectangles and pyrene, perylene, or coronene. In contrast, the small pyrazine‐containing metallarectangles 4 – 6 show no interaction in solution with this series of planar aromatic molecules.     

Parahydrogen‐Induced Polarization Transfer to 19F in Perfluorocarbons for 19F NMR Spectroscopy and MRI

Fluorinated substances are important in chemistry, industry, and the life sciences. In a new approach, parahydrogen‐induced polarization (PHIP) is applied to enhance ¹⁹F MR signals of (perfluoro‐n‐hexyl)ethene and (perfluoro‐n‐hexyl)ethane. Unexpectedly, the end‐standing CF₃ group exhibits the highest amount of polarization despite the negligible coupling to the added protons. To clarify this non‐intuitive distribution of polarization, signal enhancements in deuterated chloroform and acetone were compared and ¹⁹F–¹⁹F NOESY spectra, as well as ¹⁹F T₁ values were measured by NMR spectroscopy. By using the well separated and enhanced signal of the CF₃ group, first ¹⁹F MR images of hyperpolarized linear semifluorinated alkenes were recorded.     

Synthesis of some new 1‐acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazole

Some new compounds (E)‐3‐aryl‐1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐prop‐2‐en‐1‐ones 5a–e were prepared by 1‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐ethanone and various aromatic aldehydes. Then one pot reaction was happened by compounds 5a–e with hydrazine hydrate in acetic acid or propionic acid, respectively, to give the title compounds 1acyl‐5‐aryl‐3‐(5‐methyl‐1‐p‐tolyl‐1H‐1,2,3‐triazol‐4‐yl)‐4,5‐dihydro‐1H‐pyrazoles 6a–i . All structures were established by MS, IR, CHN, ¹H‐NMR and ¹³C‐NMR spectral data. J. Heterocyclic Chem., (2012).     

Synthesis of (3,5‐Aryl/methyl‐1H‐Pyrazol‐1‐yl)‐(5‐Arylamino‐2H‐1,2,3‐Triazol‐4‐yl)Methanone

Some new (3,5‐aryl/methyl‐1H‐pyrazol‐1‐yl)‐(5‐arylamino‐2H‐1,2,3‐triazol‐4‐yl)methanones were synthesized and characterized by ¹HNMR, ¹³C NMR, MS, IR spectra data and elemental analyses or high resolution mass spectra (HRMS). During the procedure, Dimroth rearrangement was used in this synthesis.     

含噻唑和1,2,3-三唑环的硫代磷酸肟酯的合成与生物活性

为了寻找高效、低毒的新型农用化学品,以2-氯-5-(氯甲基)噻唑为起始原料,设计合成了一系列新型含1,2,3-三唑和噻唑杂环的肟醚硫代磷酸酯衍生物,采用IR, 1H NMR, 31P NMR, MS和元素分析对其进行了结构表征。初步生物活性测试结果表明：该系列化合物具有中等程度的杀虫和杀菌活性。     

A new copper(II) supramolecular coordination polymer and a dinuclear compound with multifunctional 2‐amino‐5‐sulfobenzoic acid and flexible N‐donor ligands: synthesis,structure and characterization

Multifunctional 2‐amino‐5‐sulfobenzoic acid (H₂afsb) can exhibit a variety of roles during the construction of supramolecular coordination polymers. The pendant carboxylic acid, sulfonic acid and amino groups could not only play a role in directing bonding but could also have the potential to act as hydrogen‐bond donors and acceptors, resulting in extended high‐dimensional supramolecular networks. Two new Cu^II coordination compounds, namely catena‐poly[[[diaquacopper(II)]‐μ‐1,6‐bis(1H‐1,2,4‐triazol‐1‐yl)hexane‐κ²N⁴:N^4′] bis(3‐amino‐4‐carboxybenzenesulfonate) dihydrate], {[Cu(C₁₀H₁₆N₆)₂(H₂O)₂](C₇H₆NO₅S)₂·2H₂O}_n or {[Cu(bth)₂(H₂O)₂](Hafsb)₂·2H₂O}_n, (1), and bis(μ‐2‐amino‐5‐sulfonatobenzoato‐κ²O¹:O^1′)bis{μ‐1,2‐bis[(1H‐imidazol‐1‐yl)methyl]benzene‐κ²N³:N^3′}bis[aquacopper(II)] trihydrate, [Cu₂(C₇H₅NO₅S)₂(C₁₄H₁₄N₄)₂(H₂O)₂]·3H₂O or [Cu₂(afsb)₂(obix)₂(H₂O)₂]·3H₂O, (2), have been obtained through the assembly between H₂afsb and the Cu^II ion in the presence of the flexible N‐donor ligands 1,6‐bis(1H‐1,2,4‐triazol‐1‐yl)hexane (bth) and 1,2‐bis[(1H‐1,2,4‐triazol‐1‐yl)methyl]benzene (obix), respectively. Compound (1) consists of a cationic coordination polymeric chain and 3‐amino‐4‐carboxybenzenesulfonate (Hafsb⁻) anions. Compound (2) exhibits an asymmetric dinuclear structure. There are hydrogen‐bonded networks within the lattices of (1) and (2). Interestingly, both (1) and (2) exhibit reversible dehydration–rehydration behaviour.     

Two new cadmium(II) coordination polymers based on bis(1,2,4‐triazol‐1‐yl)alkane ligands and pyrazine‐2,3‐dicarboxylic acid

Assemblies of pyrazine‐2,3‐dicarboxylic acid and Cd^II in the presence of bis(1,2,4‐triazol‐1‐yl)butane or bis(1,2,4‐triazol‐1‐yl)ethane under ambient conditions yielded two new coordination polymers, namely poly[[tetraaqua[μ₂‐1,4‐bis(1,2,4‐triazol‐1‐yl)butane‐κ²N⁴:N^4′]bis(μ₂‐pyrazine‐2,3‐dicarboxylato‐κ³N¹,O²:O³)dicadmium(II)] dihydrate], {[Cd₂(C₆H₂N₂O₄)₂(C₈H₁₂N₆)(H₂O)₄]·2H₂O}_n, (I), and poly[[diaqua[μ₂‐1,2‐bis(1,2,4‐triazol‐1‐yl)ethane‐κ²N⁴:N^4′]bis(μ₃‐pyrazine‐2,3‐dicarboxylato‐κ⁴N¹,O²:O³:O^3′)dicadmium(II)] dihydrate], {[Cd₂(C₆H₂N₂O₄)₂(C₆H₈N₆)(H₂O)₂]·2H₂O}_n, (II). Complex (I) displays an interesting two‐dimensional wave‐like structure and forms a distinct extended three‐dimensional supramolecular structure with the help of O—H...N and O—H...O hydrogen bonds. Complex (II) has a three‐dimensional framework structure in which hydrogen bonds of the O—H...N and O—H...O types are found.     

Synthesis of novel isoindolone‐based medium‐sized macromolecules and triazole containing heterocyclic compounds

A series of novel isoindolone‐based macromolecules of medium‐sized heterocyclic rings, such as 7,8‐dihydro‐6H‐benzo[4,5][1,6,3]dioxazonino[2,3‐a]isoindol‐14(9aH)‐one derivatives ( 5a‐l ), were synthesized and its frame work incorporating with a triazole moiety on phenol, ie, 2‐(4‐((1‐(2‐methoxyphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methoxy)phenyl)isoindoline‐1,3‐dione ( 9a‐f ) and also a triazole moiety on carboxylic acid, ie, (1‐(2‐methoxyphenyl)‐1H‐1,2,3‐triazol‐4‐yl)methyl 4‐(1,3‐dioxoisoindolin‐2‐yl)benzoate derivatives ( 13a‐e ) with various substitutions on aryl ring system have synthesized. All the synthesized compounds were characterized and confirmed with IR, ¹H NMR_, ¹³C NMR, and ESI mass spectral analysis.     

Synthesis of 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas and their inhibition activity to acetylcholinesterase and butyrylcholinesterase

A series of novel 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas were synthesized by the condensation of (1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethanamine with substituted phenyl isocyanates under mild conditions. Their structures were confirmed ¹H, ¹³C, and ¹⁹F NMR spectra, and elemental analyses. The optical activities were confirmed by optical rotation measurements. The inhibition activity of 1‐[(1R)‐1‐(6‐fluoro‐1,3‐benzothiazol‐2‐yl)ethyl]‐3‐substituted phenyl ureas to acetylcholinesterase (ACHE) and butyrylcholinesterase (BCHE) was also tested. Preliminary bioassay indicated that the target ureas displayed excellent acetylcholinesterase and butyrylcholinesterase inhibition activity. J. Heterocyclic Chem., 2011.     

Three derivatives of 4‐fluoro‐5‐sulfonylisoquinoline

In 4‐fluoroisoquinoline‐5‐sulfonyl chloride, C₉H₅ClFNO₂S, (I), one of the two sulfonyl O atoms lies approximately on the isoquinoline plane as a result of minimizing the steric repulsion between the chlorosulfonyl group and the neighbouring F atom. In (S)‐(−)‐4‐fluoro‐N‐(1‐hydroxypropan‐2‐yl)isoquinoline‐5‐sulfonamide, C₁₂H₁₃FN₂O₃S, (II), there are two crystallographically independent molecules (Z′ = 2). The molecular conformations of these two molecules differ in that the amine group of one forms an intramolecular bifurcated hydrogen bond with the F and OH groups, whilst the other forms only a single intramolecular N—H...F hydrogen bond. The N—H...F hydrogen bonds correspond to weak coupling between the N(H) and ¹⁹F nuclei, observed in the ¹H NMR solution‐state spectra. In (S)‐(−)‐4‐[(4‐fluoroisoquinolin‐5‐yl)sulfonyl]‐3‐methyl‐1,4‐diazepan‐1‐ium chloride, C₁₅H₁₉FN₃O₂S⁺·Cl⁻, (III), the isoquinoline plane is slightly deformed, suggestive of a steric effect induced by the bulky substituent on the sulfonyl group.     

Primary Studies on Variation in Position of Trifluoromethyl Groups in Several Aromatic Group‐14 Derivatives by 19F‐NMR Spectroscopy

Variation in the position of CF₃ groups in several aromatic Group‐14 compounds was studied by ¹⁹F‐NMR spectroscopy. In these compounds R_nECl_4?n (n=1 or 2; E=Si, Ge, or Sn; R=2,4,6‐(CF₃)₃C₆H₂ (=Ar), 2,6‐(CF₃)₂C₆H₃ (=Ar′), or 2,4‐(CF₃)₂C₆H₃ (=Ar″)), Ar, Ar′, and Ar″ are all bulky, strongly electron‐withdrawing ligands. The ¹⁹F‐NMR studies of the variation in position of the CF₃ substituents in these compounds as revealed by chemical shifts could be correlated with the electronegativities of the central elements E, and with intramolecular E–F interactions derived from single‐crystal X‐ray diffraction data. These interactions are considered to play an important role in the stabilization of these compounds.