Synthesis and biological activities of new 1H-1,2,4-triazole derivatives containing ferrocenyl moiety

Some new 1H-1,2,4-triazole derivatives containing ferrocenyl moiety were synthesized in various yields by the condensation of ferrocenecarboxaldehyde with 1-(1H-1,2,4-triazol-1-yl)-3-aryl-2-one in toluene. Their structures of all these new compounds have been confirmed with ¹H NMR, IR, MS and elemental analysis. Their results of bioassay showed that some title compounds exhibited some degree of antifungal and plant growth regulatory activities.     

On the explosive properties of 1H-benzotriazole and 1H-1,2,3-triazole

For 1H-benzotriazole, no explosive properties are observable, but the relative high exothermic decomposition energy of 1590 J/g should be kept in mind. Nevertheless, an endothermic melting barrier at 100 °C ensures safe handling at lower temperatures. For 1H-1,2,3-triazole, the exothermic decomposition energy is as high as 2600 J/g, but explosive properties are also not detectable. Therefore, both reagents are hazardous with regard to the exothermic decomposition potential and can be handled safely with precautions.     

Synthesis, structures and biological activity research of novel ferrocenyl-containing 1H-1,2,4-triazole derivatives

Novel ferrocene-containing propenones have been synthesized from acetylferrocene via a Mannich-type intermediate. Sequential condensation cyclization of these propenones with phenylhydrazine afforded highly substituted 4,5-dihydropyrazole derivatives, which structures have been characterized by spectra data and single crystal X-ray diffraction analysis. In addition, these new ferrocene-containing derivatives have been evaluated for in vitro fungicidal activities against five selected fungi.     

Synthesis of phenoxyquinolin-4(1H)-one through copper(II)-mediated cross-coupling of phenylboronic acid and hydroxyquinolin-4(1H)-one

A synthetic method to prepare novel phenoxyquinolin-4(1H)-one compounds via cross-coupling of hydroxyquinolin-4(1H)-one with a variety of phenylboronic acids is reported. The reaction is mediated by copper(II) acetate at room temperature in air and is tolerant of several functional groups on the phenylboronic acids.     

Highly regioselective heterocyclization reactions of 1H-1,2,4-triazole-3-thiols with chloroacetylenephosphonates

1-Chloroacetylene-2-phosphonates react with 1H-1,2,4-triazole-3-thiols in anhydrous acetonitrile with high regioselectivity to form the fused heterocycles, 6-(dialkoxyphosphoryl)-3H-thiazolo[3,2-b][1,2,4]triazol-7-ylium chlorides 1-5. A significant difference from the previously known reactions of binucleophiles with haloacetylenes is the involvement of both acetylenic carbon atoms in the heterocycle formation. A reaction mechanism is hypothesized that assumes the formation of a sulfenium cation at the acetylene C-1 atom followed by attack of the C-2 atom by the ring N-2 atom. Compounds 1-5 easily lose one alkyl group from the dialkoxyphosphoryl fragment to form zwitterions (e.g., 6-8) which further can be transformed into inner salts 9 and 10 when heated with concentrated hydrochloric acid.     

Regioselective alkylation reactions of 2,4-diphenyl-3H-1-benzazepine give either 3-alkyl-3H-1-benzazepines or 1-alkyl-1H-1-benzazepines

2,4-Diphenyl-3H-1-benzazepine is deprotonated with either LDA or KHMDS. The resulting anion is alkylated with alkyl halides or MeOTs, giving either products of alkylation at C3, or at N, or a mixture of both. The regioselectivity depends on the base, presence of the complexing agent HMPA, and the leaving group of the alkylating agent. Using MeI as alkylating agent gives exclusively the C3-methylated product, while using MeOTs gives exclusively the N-methylated product. The N-alkylated products show evidence of stereodynamic behavior in their NMR spectra.     

α-(3,7-Dioxa-r-1-azabicyclo[3.3.0]oct-c-5-ylmethoxy)-diazines. Part 2: Functionalisation via directed ortho-metallation and cross-coupling reactions

The functionalisation of the title compounds via regioselective Directed ortho-Metallation (DoM) and cross-coupling reactions is studied. The compatibility of the 3,7-DiOxa-r-1-AzaBicyclo[3.3.0]Oct-c-5-ylmethoxy system (DOABO-CH₂O) to typical reaction conditions is established. Its role as Directed ortho-Metallation Group (DoMG) is examined, including competition with classical DoMGs, chlorine and methoxy. The chelating ability of some functionalised terms such as DOABO-CH₂O substituting chiral diarylmethanols and polyaza analogues of 2,6-terpyridine is discussed as intramolecular steric relationships determining configuration and aptitude to bind selectively transition metals, respectively.     

A novel method for thiiranation of alkenes with 1,1′-dithiobis(1H-1,2,4-triazole)

Eight alkenes reacted with 1,1′-dithiobis(1H-1,2,4-triazole) 4 at −15 °C to form the corresponding thiiranes in moderate to good yields. The thiiranations of anti- and syn-9,9′-bibenzonorbornenylidenes and cis- and trans-cyclooctenes with 4 proceeded with retention of configuration of the starting alkenes.     

Magnetically recoverable copper ferrite catalyzed cascade synthesis of 4-Aryl-1H-1,2,3-triazoles under microwave irradiation

Magnetically active CuFe₂O₄ catalyzed cascade synthesis of 4-Aryl-1H-1,2,3-triazoles under microwave irradiation starting from aromatic aldehydes, sodium azide and nitromethane has been developed and demonstrated here. The catalyst system needed for the purpose was prepared following a procedure by A. Dandiya et al. with a slight modification and was characterized using FT-IR, XRD, SEM-EDX and TEM analysis. The most notable advantage of the developed methodology is the excellent time economy to carry out the transformation. Other features include simple operating procedure, wide substrate coverage and easy recovery of the catalyst. Reusability of the catalyst has been tested and found to be very satisfactory up to sixth cycle without significant loss in efficiency. All the synthesized compounds have been characterized using FTIR, ¹H & ¹³CNMR spectroscopy, HRMS.     

Cobalt-catalyzed cross-coupling reactions of alkyl halides with aryl Grignard reagents and their application to sequential radical cyclization/cross-coupling reactions

Reactions of alkyl halides with arylmagnesium bromides in the presence of cobalt(II)(diphosphine) complexes are discussed. Treatment of 1-bromooctane with phenylmagnesium bromide with the aid of a catalytic amount of CoCl₂(dppp) [DPPP=1,3-bis(diphenylphosphino)propane] yielded octylbenzene in good yield. The reaction mechanism would include single electron transfer from an electron-rich cobalt complex to alkyl halide to generate the corresponding alkyl radical. The mechanism was justified by CoCl₂(dppe)-catalyzed [DPPE=1,2-bis(diphenylphosphino)ethane] sequential radical cyclization/cross-coupling reactions of 6-halo-1-hexene derivatives that yielded benzyl-substituted cyclopentane skeletons.     

Selectivity between N-1 and N-7 nucleosides: regioselective synthesis of BMK-Y101, a potent cdk7 and 9 inhibitor

BMK-Y101 is a new pyrrolo[2,3-d]pyrimidine-based potent cdk7 and 9 inhibitor, which is characterized by an intriguing structural feature of N-1 nucleoside, departing from previously reported N-7 nucleoside Cdk inhibitor, xylocydine. Though N-1 nucleosides have appeared in the literature, they have often been considered as kinetic products and thus intermediates of N-7 glycosylation. In the course of the synthetic studies of xylocydine derivatives, we have developed a highly regioselective method to obtain the N-1 nucleoside. The origin of the selectivity is apparently based on the reactivity of the silylated nucleobase and the stability of the resulting N-1 nucleoside. The choice of BSA as a silylating agent was critical in securing the N-1 nucleoside, BMK-Y101. On the other hand, proper selection of reaction conditions promoting transglycosylation provides an efficient route to N-7 nucleosides.     

Palladium-catalyzed Suzuki cross-coupling reactions in a microemulsion

An enhancement of palladium-catalyzed Suzuki cross-coupling reactions between substrates possessing long-chain alkyl or oxyalkyl substituents in two-phase media, in the presence of sodium dodecylsulfate, is shown. Quantitative evaluations of the influence of SDS on the reaction rates were determined.     

First cross-coupling reactions on tetrazines

[reaction: see text] A series of substituted chlorotetrazines were reacted with different terminal alkynes under Sonogashira or Negishi coupling conditions to furnish alkynyl-tetrazines in good to moderate yield. The electron-donating properties of the substituent on the tetrazine core were found to have a significant influence on the success of the reaction. These results constitute the first cross-coupling reactions on tetrazines.     

Preparation of 2,2-difluoro-1-trialkylsilylethenylstannanes and their cross-coupling reactions

Reaction of 2 with bis(tributyltin) in the presence of 3 mol % Pd₂(dba)₃, 6 mol % XPhos, and 30 equiv of LiBr in wet and air bubbled THF at reflux for 8 h afforded the desired products 3 in 73–74% yields. The cross-coupling reaction of 3a with aryl iodides in the presence of 10 mol % Pd(PPh₃)₄ and 10 mol % CuI afforded the coupled products 4a–p in 47–90% yields. The coupling reaction of 3b with various alkynyl bromides having aryl-, alkyl, or trialkylsilyl group also afforded the corresponding 1,3-enynes 5a–g in 61–77% yields.     

An efficient route to diverse H-pyrazolo[5,1-a]isoquinolines via sequential multi-component/cross-coupling reactions

Multi-component reaction of 2-alkynylbenzaldehyde, sulfonohydrazide, electrophile (bromine or iodine), and ketone or aldehyde under mild conditions proceeds smoothly to afford the functionalized H-pyrazolo[5,1-a]isoquinolines in good yields. This one-pot process involves intermolecular condensation, electrophilic cyclization, nucleophilic addition, intramolecular condensation, and aromatization. The resulting halo-containing H-pyrazolo[5,1-a]isoquinolines could be further elaborated via palladium-catalyzed cross-coupling reactions.     

Synthesis of biphenylamines via Suzuki-Miyaura cross-coupling reactions

A small library of meta- and para-biphenylamines substituted by various alkyl, alkoxy, phenoxy, or halogeno groups on their aromatic rings was synthesized via Suzuki-Miyaura cross-coupling between bromoanilines and arylboronic acids using palladium catalysts. The experimental conditions were carefully adjusted to accommodate a wide range of substituents, in terms of electron-withdrawing or -donating ability and steric bulk. In some cases, protection and deprotection of the amine function via its trifluoroacetamide were added to the reaction sequence in order to facilitate the cross-coupling step.     

Regioselective alkylation of 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole

Alkylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole and 1H-7-ethoxycarbonyl-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole using different alkylating agents leads regioselectively to 1-N-alkylated products. The hydrolysis-decarboxylation of 1,6-dimethyl-7-ethoxycarbonyl-pyrazolo[5,1-c][1,2,4]triazole yields a compound identical with that obtained by the direct methylation of 1H-6-methyl-3-phenyl-pyrazolo[5,1-c][1,2,4]triazole. The 1-N-alkylation is confirmed by NMR spectroscopy and mass spectrometry.     

Divergent synthesis of arylated pyridin-2(1H)-one derivatives via metal-catalysed cross-coupling processes

1,5-Di(hetero)arylated-pyridin-2(1H)-one derivatives have been readily obtained in good yields starting from 2-fluoro-5-pyridylboronic acid. The sequence comprises three steps: (i) palladium-catalysed Suzuki-Miyaura reaction; (ii) base-catalysed hydrolysis; (iii) copper-catalysed C-N coupling. X-ray crystal structures are reported for selected pyridin-2(1H)-one derivatives. These compounds are of interest as new scaffolds for drug discovery.     

Synthesis of arylated chalcone derivatives via palladium cross-coupling reactions

A useful protocol for arylation of the olefin double bond of chalcones to afford tri- and tetra-substituted chalcone derivatives is reported. The protocol begins with the Heck reaction between chalcones and aryl iodides providing β-arylchalcones. This reaction tolerates various functional groups on both rings, as well as deactivated aryl iodides. The products are obtained in moderate to excellent yields and the (E)-β-arylchalcones (E:Z?>?96:4) can be isolated via precipitation. Competitive Heck reactions pointed to a significant effect of ring one substituents on the reaction rate, while substituents on ring two have a much smaller effect. To access α,β-diarylchalcones, a sequential bromination-Suzuki cross coupling strategy was applied to the β-arylated compounds which afforded double arylated chalcone derivatives in 60–99% yield over two steps.