Improvement of humic acid (HA) removal using a new inorganic-organic composite coagulant: α-costic acid as a modifier of polyaluminum chloride properties.

In this work, α-costic acid (αCA), a plant sesquiterpenoid from Dittrichia viscosa, was grafted into polyaluminum chloride (PAC), forming a new eco-sustainable composite coagulant PAC-αCA with improved functionality. The α-costic acid fraction grafted into the PAC and the distribution of aluminum forms in the composite coagulant were evaluated for their effectiveness in removing bentonite and humic acid from synthetic water. The interaction mechanism between PAC and α-CA was examined by the Al-Ferron time spectrophotometric method, density functional theory (DFT), and FTIR analysis. By monitoring the aluminum speciation in the composite coagulant PAC-αCA, it was discovered that the introduction of α-CA impacted the distribution of various aluminum forms, including mononuclear Ala, highly polymeric Alb, colloidal, and medium polymeric Alc. The theoretical analysis identified the Alb species as particularly sensitive to reacting with α-CA. Furthermore, coagulation performance tests demonstrated that increasing the percentage of α-CA and promoting the prevalence of Alb and Alc species over Ala species in PAC-αCA led to improved removal of turbidity and UV254. This study provides an attractive and practical option for water treatment plants to remove colloidal suspensions in raw water effectively.

Access and Modulation of Substituted Pyrrolo[3,4-c]pyrazole-4,6-(2H,5H)-diones.

The first access to polyfunctionnalized pyrrolo[3,4-c]pyrazole-4,6-(2H,5H)-dione derivatives is reported. The series were generated from diethyl acetylenedicarboxylate and arylhydrazines, which afforded the key intermediates bearing two functional positions. The annellation to generate the maleimide moiety of the bicycle was studied. Moreover, an efficient palladium-catalyzed C-C and C-N bond formation via Suzuki-Miyaura or Buchwald-Hartwig coupling reactions in C-6 position was investigated from 6-chloropyrrolo[3,4-c]pyrazole-4,6-(2H,5H)-diones. This method provides novel access to various 1,6 di-substituted pyrrolo[3,4-c] pyrazole-4,6-(2H,5H)-diones.

Efficient Synthesis of 1H-Benzo[4,5]imidazo[1,2-c][1,3]oxazin-1-one Derivatives Using Ag2CO3/TFA-Catalyzed 6-endo-dig Cyclization: Reaction Scope and Mechanistic Study.

A small library of 1H-benzo[4,5]imidazo[1,2-c][1,3]oxazin-1-one derivatives was prepared in good to excellent yields, involving a Ag2CO3/TFA-catalyzed intramolecular oxacyclization of N-Boc-2-alkynylbenzimidazole substrates. In all experiments, the 6-endo-dig cyclization was exclusively achieved since the possible 5-exo-dig heterocycle was not observed, indicating the high regioselectivity of this process. The scope and limitations of the silver catalyzed 6-endo-dig cyclization of N-Boc-2-alkynylbenzimidazoles as substrates, bearing various substituents, were investigated. While ZnCl2 has shown limits for alkynes with an aromatic substituent, Ag2CO3/TFA demonstrated its effectiveness and compatibility regardless of the nature of the starting alkyne (aliphatic, aromatic or heteroaromatic), providing a practical regioselective access to structurally diverse 1H-benzo[4,5]imidazo[1,2-c][1,3]oxazin-1-ones in good yields. Moreover, the rationalization of oxacyclization selectivity in favor of 6-endo-dig over 5-exo-dig was explained by a complementary computational study.

D-π-A-Type Pyrazolo[1,5-a]pyrimidine-Based Hole-Transporting Materials for Perovskite Solar Cells: Effect of the Functionalization Position.

Donor−acceptor (D−A) small molecules are regarded as promising hole-transporting materials for perovskite solar cells (PSCs) due to their tunable optoelectronic properties. This paper reports the design, synthesis and characterization of three novel isomeric D-π-A small molecules PY1, PY2 and PY3. The chemical structures of the molecules consist of a pyrazolo[1,5-a]pyrimidine acceptor core functionalized with one 3,6-bis(4,4'-dimethoxydiphenylamino)carbazole (3,6-CzDMPA) donor moiety via a phenyl π-spacer at the 3, 5 and 7 positions, respectively. The isolated compounds possess suitable energy levels, sufficient thermal stability (Td > 400 °C), molecular glass behavior with Tg values in the range of 127−136 °C slightly higher than that of the reference material Spiro-OMeTAD (126 °C) and acceptable hydrophobicity. Undoped PY1 demonstrates the highest hole mobility (3 × 10−6 cm2 V−1 s−1) compared to PY2 and PY3 (1.3 × 10−6 cm2 V−1 s−1). The whole isomers were incorporated as doped HTMs in planar n-i-p PSCs based on double cation perovskite FA0.85Cs0.15Pb(I0.85Br0.15)3. The non-optimized device fabricated using PY1 exhibited a power conversion efficiency (PCE) of 12.41%, similar to that obtained using the reference, Spiro-OMeTAD, which demonstrated a maximum PCE of 12.58% under the same conditions. The PY2 and PY3 materials demonstrated slightly lower performance in device configuration, with relatively moderate PCEs of 10.21% and 10.82%, respectively, and slight hysteresis behavior (−0.01 and 0.02). The preliminary stability testing of PSCs is also described. The PY1-based device exhibited better stability than the device using Spiro-OMeTAD, which could be related to its slightly superior hydrophobic character preventing water diffusion into the perovskite layer.

Molecular Characterization of Gene-Mediated Resistance and Susceptibility of ESKAPE Clinical Isolates to Cistus monspeliensis L. and Cistus salviifolius L. Extracts.

Background: Multidrug resistance (MDR) and extensively drug-resistant (XDR) are now the biggest threats to human beings. Alternative antimicrobial regimens to conventional antibiotic paradigms are extensively searched. Although Cistus extracts have long been used for infections in traditional folk medicines around the world, their efficacy against resistant bacteria still needs to be elucidated. We aim to investigate the antibiotic susceptibility profiles of clinical strains Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter cloacae (acronym "ESKAPE"), and their resistance mechanisms by PCR, as well as their sensitivity to C. monspeliensis (CM) and C. salviifolius (CS) methanol extracts and their fractions. Methods: Antibiotic susceptibility profile and resistance mechanism were done by antibiogram and PCR. Fractions of CM and CS were obtained using maceration and Soxhlet; their antibacterial activities were evaluated by determining inhibition zone diameter (IZD), minimum inhibitory concentration (MIC), and minimum bactericidal concentration (MBC). Results: Results revealed that all strains were XDR except S. aureus, which was MDR. The PCR indicates the presence of gene-mediated resistance (bla CTX-M, bla SHV, bla OXA-48, bla NDM, bla OXA-51, bla OXA-58, bla IMP, bla VIM, and bla mecA). Also, maceration was slightly better for bioactivity preservation. Overall, the extracts of CM (IZD = 20 mm, MIC = 0.01 mg/mL) were more active than those of CS. All extracts inhibited MRSA (methicillin-resistant Staphylococcus aureus) and ERV (Enterococcus faecium Vancomycin-Resistant) with interesting MICs. The ethyl acetate fraction manifested great efficacy against all strains. Monoterpene hydrocarbons and sesquiterpenes oxygenated were the chemical classes of compounds dominating the analyzed fractions. Viridiflorol was the major compound in ethyl acetate fractions of 59.84% and 70.77% for CM and CS, respectively. Conclusions: The superior activity of extracts to conventional antibiotics was seen for the first time in the pathogens group, and their bactericidal effect could be a promising alternative for developing clinical antibacterial agents against MDR and XDR ESKAPE bacteria.

Antifungal and Cytotoxic Activity of Diterpenes and Bisnorsesquiterpenoides from the Latex of Euphorbia resinifera Berg.

Euphorbia resinifera latex has been extensively utilized in traditional medicine due to its range of bioactivities. Chromatographic separations on silica gel of ethanol extract of E. resinifera latex led to the development of a new procedure for isolating resiniferatoxin (4) via dried E. resinifera latex and the identification of nine compounds. Among these, catechol (7), protocatechuic acid (8) and 3,4-dihydroxyphenylacetic acid (9), known phenolic compounds, were identified for the first time in E. resinifera latex. Herein we investigated the effects of major compounds of the latex of E. resinifera on the yeast Saccharomyces cerevisiae, on the growth of Aspergillus carbonarius, a widespread fungal contaminant, and on the breast cancer cell line MCF7 as well as on MCF10A normal breast cells. 12-deoxyphorbol-13-isobutyrate-20-acetate (2) had an inhibiting effect on the growth of A. carbonarius, and 7-p-metoxyphenylacetate-3,8,12-triacetate ingol (3) showed a negative effect on yeast cell growth and also a cytotoxic effect on breast cancer cell line MCF7, but not on MCF10A cells. Deglucosyl euphorbioside A (5) and euphorbioside A (6) showed a discoloration effect that was possibly related to mitochondrial functionality in yeast, and also cytotoxicity only on the cancer cell line that was tested. Interestingly, treatment of MCF7 cells with 7-p-metoxyphenylacetate-3,8,12-triacetate ingol (3) and deglucosyl euphorbioside A (5) not only led to a specific cytotoxic effect but also to the increase in the level of intracellular ROS.

Design, Synthesis, and Biological Evaluation of Novel Tomentosin Derivatives in NMDA-Induced Excitotoxicity.

N-methyl-D-aspartate (NMDA) receptor stimulation may lead to excitotoxicity, which triggers neuronal death in brain disorders. In addition to current clinical therapeutic approaches, treatment strategies by phytochemicals or their derivatives are under investigation for neurodegenerative diseases. In the present study, novel amino and 1,2,3-triazole derivatives of tomentosin were prepared and tested for their protective and anti-apoptotic effects in NMDA-induced excitotoxicity. Amino-tomentosin derivatives were generated through a diastereoselective conjugate addition of several secondary amines to the α-methylene-γ-butyrolactone function, while the 1,2,3-triazolo-tomentosin was prepared by a regioselective Michael-type addition carried out in the presence of trimethylsilyl azide (TMSN3) and the α-methylene-γ-lactone function. The intermediate key thus obtained underwent 1,3-dipolar Huisgen cycloaddition using a wide range of terminal alkynes. The possible effects of the derivatives on cell viability and free-radical production following NMDA treatment were measured by Water-Soluble Tetrazolium Salts (WST-1) and Dichlorofluorescein Diacetate (DCF-DA) assays, respectively. The alterations in apoptosis-related proteins were examined by Western blot technique. Our study provides evidence that synthesized triazolo- and amino-tomentosin derivatives show neuroprotective effects by increasing cellular viability, decreasing ROS production, and increasing the Bcl-2/Bax ratio in NMDA-induced excitotoxicity. The findings highlight particularly 2e, 2g, and 6d as potential regulators and neuroprotective agents in NMDA overactivation.

Near-Infrared Emitting Poly(amidoamine) Dendrimers with an Anthraquinone Core toward Versatile Non-Invasive Biological Imaging.

Today, there is a very strong demand for versatile near-infrared (NIR) imaging agents suitable for non-invasive optical imaging in living organisms (in vivo imaging). Here, we created a family of NIR-emitting macromolecules that take advantage of the unique structure of dendrimers. In contrast to existing fluorescent dendrimers bearing fluorophores at their periphery or in their cavities, a NIR fluorescent structure is incorporated into the core of the dendrimer. Using the poly(amidoamine) dendrimer structure, we want to promote the biocompatibility of the NIR-emissive system and to have functional groups available at the periphery to obtain specific biological functionalities such as the ability to deliver drugs or for targeting a biological location. We report here the divergent synthesis and characterization by NMR and mass spectrometries of poly(amidoamine) dendrimers derived from the fluorescent NIR-emitting anthraquinone core (AQ-PAMAF). AQ-PAMAFs ranging from the generation -0.5 up to 3 were synthesized with a good level of control resulting in homogeneous and complete dendrimers. Absorption, excitation, and emission spectra, as well as quantum yields, of AQ-PAMAFs have been determined in aqueous solutions and compared with the corresponding properties of the AQ-core. It has been demonstrated that the absorption bands of AQ-PAMAFs range from UV to 750 nm while emission is observed in the range of 650-950 nm. Fluorescence macroscopy experiments confirmed that the NIR signal of AQ-PAMAFs can be detected with a satisfactory signal-to-noise ratio in aqueous solution, in blood, and through 1 mm thick tissue-mimicking phantom. The results show that our approach is highly promising for the design of an unprecedented generation of versatile NIR-emitting agents.

A Ag2CO3/TFA-catalyzed intramolecular annulation approach to imidazo[1,2-c][1,3]oxazin-5-one derivatives.

A series of 2,7-disubstituted 3-methylimidazo[1,2-c][1,3]oxazin-5-ones were synthesized in good yields via Ag2CO3/TFA-mediated intramolecular annulation of N-Boc-2-alkynyl-4-bromo(alkynyl)-5-methylimidazoles. This methodology was carried out in the presence of a catalytic amount of silver carbonate and trifluoroacetic acid in dichloroethane at 60 °C. In all experiments, only the six-membered ring product was obtained since the possible five-membered compound was not observed, proving the high regioselectivity of this approach. A complementary computational study was performed in order to rationalize the mechanism of 6-endo-dig heterocycle formation. In addition, 2-bromo-3-methyl-7-phenylimidazo[1,2-c][1,3]oxazin-5-one was used as a building block to synthesize a small library of new 2-substituted imidazo[1,2-c][1,3]oxazin-5-one derivatives through the Suzuki, Sonogashira and Heck cross coupling reactions.

Chemical composition, antibacterial, antioxidant and insecticidal activities of moroccan Thapsia transtagana essential oil.

INTRODUCTION: The use of chemical products to neutralize microorganisms has always been a subject of discussion and research for alternative solutions, indeed, the use of essential oils has been a promising natural methodology. METHODS: In our study we used the essential oils from different parts of Thapsia transtagana (Apiaceae), obtained by hydrodistillation, were identified and using Gas chromatography-mass spectrometry (GC-MS) and Gas Chromatography-Flame Ionization Detection (GC/FID) methods and evaluated against several bacteria of Gram- and Gram + bacteria. Disk diffusion, Minimum Inhibitory Concentration (MIC) and Minimum Microbicidal Concentration (MMC) methods have been used. Free radical-scavenging activity and insecticidal activity of Thapsia transtagana essential oils were also identified. RESULTS: Majority products from different parts of Thapsia transtagana essential oil identified by GC-MS and GC/FID methods are 2,6-Dimethylnaphthalene, Pinane and Hexahydrofarnesyl acetone. The highest activity was found against Staphylococcus aureus using inflorescence essential oil with minimal inhibitory concentration value for 0,56 µg/µL. Insecticidal activity was also the subject of this study, roots and inflorescence essential oils demonstrated to have a remarkable potent against Acanthoscelides obtectus and Sitophilus oryzae using contact assessment, inhalation assessment and ingestion assessment tests. Insecticidal activity assay results showed a significant enhancement of mortality in both test insect pest on increasing the dose and exposure period. In the other hand, the different essential oils of Thapsia transtagana were evaluated for their radical scavenging activities by means of the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay. The strongest scavenging activity was observed in inflorescences essential oil fraction scavenged radicals effectively at 100% using 500 mgL-1 concentration. CONCLUSION: Its essential oils were proved to have strong antimicrobial, insecticidal and antioxidant activities that allows it to be used by the pharmaceutical and cosmetic industries as natural preservative.

A Review on Cistus sp.: Phytochemical and Antimicrobial Activities.

Resistance to drugs is reaching alarming levels and is placing human health at risk. With the lack of new antimicrobials drugs, infectious diseases are becoming harder to treat. Hence, there is an increasing awareness of active phytochemicals with therapeutic functions. The tremendous research interest on the Cistus L. genus includes numerous plants used in traditional medicine by people living around the Mediterranean Sea, also resulted in some interesting discoveries and written literature. This review aimed at gathering scientific literature about Cistus species, describing phytochemical profiles and the various pharmacological activities. We also extensively reviewed the antimicrobial activities, including antiviral, antiparasitic, antifungal, and antibacterial potentials of Essential Oils (EO), raw extracts as well as isolated compounds. Mechanisms of action along with methods used are also investigated in this review. Considering the findings of the Cistus species extracts, this genus offers an adequate reserve of active phytochemicals since many have been used to create drugs. Therefore, this review work can serve society by providing a global view on Cistus L. sp. regarding pharmacological potentials and their chemical profiles.

Design, synthesis, and evaluation of cytotoxic activities of arylnaphthalene lignans and aza-analogs.

A concise and versatile synthetic strategy for the total synthesis of arylnaphthalene lignans and aza-analogs was developed. The main objective was to develop synthetic tactics for the creation of the lactone and lactam unit that would give access to an array of synthetic, natural, and/or bioactive compounds through rather simple chemical manipulation. The flexibility and potentiality of these new processes were further illustrated by the total synthesis of retrojusticidin B (13b), justicidin C (14b), and methoxy-vitedoamine A (22a). In this study, a series of novel aryl-naphthalene lignans and aza-analogs were synthesized, and the cytotoxic activities of all compounds on cancer cell growth were evaluated. The target compounds were structurally characterized by 1 H NMR (nuclear magnetic resonance), 13 C NMR, infrared, high-resolution mass spectrometry, and X-ray crystallography. The IC50 values of these compounds on five tumor cell lines (A549, HS683, MCF-7, SK-MEL-28, and B16-F1) were obtained by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) colorimetric assay. Five of the compounds exhibited excellent activity compared to 5-fluorouracil and etoposide against the five cell lines tested, with IC50 values ranging from 1 to 10 µM.

Efficient microwave-assisted Suzuki-Miyaura cross-coupling reaction of 3-bromo pyrazolo[1,5-a]pyrimidin-5(4H)-one: towards a new access to 3,5-diarylated 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidine derivatives.

A convenient and efficient synthetic route to C3-arylated 7-trifluoromethylpyrazolo[1,5-a]pyrimidin-5-one derivatives has been reported starting from 3-bromo-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-one through a Suzuki-Miyaura cross-coupling reaction. The arylation (heteroarylation) strategy can be performed using a wide variety of aryl and heteroaryl boronic acids and requiring a tandem catalyst XPhosPdG2/XPhos to avoid the debromination reaction. These optimized conditions were successfully extended to the synthesis of 7-, 8- and 9-arylated pyrimido[1,2-b]indazol-2-ones from their corresponding brominated starting materials. Furthermore, the second C-5 arylation of C3-arylated pyrazolo[1,5-a]pyrimidin-5-ones was achieved under standard Suzuki-Miyaura cross-coupling conditions, after activating the C-O bond of the lactam function with PyBroP, giving access to a small library of 3,5-diarylated 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidines in good to excellent yields. The interest of this approach has been highlighted by the synthesis of a known anti-inflammatory agent. Additionally, a preliminary biological evaluation has revealed that a number of derivatives display micromolar IC50 values against monoamine oxidase B, an important target in the field of neurodegenerative disorders.

A regioselective C7 bromination and C7 palladium-catalyzed Suzuki-Miyaura cross-coupling arylation of 4-substituted NH-free indazoles.

A direct and efficient regioselective C7-bromination of 4-substituted 1H-indazole has been achieved. Subsequently, a successful palladium-mediated Suzuki-Miyaura reaction of C7-bromo-4-substituted-1H-indazoles with boronic acids has been performed under optimized reaction conditions. A series of new C7 arylated 4-substituted 1H-indazoles was obtained in moderate to good yields.

Valorization of Opuntia ficus-Indica Pads and Steel Industry FeCl3-Rich Rejection for Removing Surfactant and Phenol from Oil Refinery Wastewater Through Coagulation-Flocculation.

BACKGROUND: Refinement of crude vegetable oil generates a large amount of wastewater and is a source of water pollution due to the presence of surfactants and phenols. Phenols are toxic aromatic compounds that can be lethal to fauna and flora, entraining the deceleration or blocking of the self-purification of biological treatments. In addition, surfactants can limit biological processes by inhibiting microorganisms that degrade organic matter. OBJECTIVES: The aim of the present study was to evaluate the treatment of refinery rejects loaded with phenols and detergents by coagulation flocculation using cactus pads (genus Opuntia) as a bio-flocculant and 30% iron(III) chloride (FeCl3) for surfactant and phenol removal. In addition, operating costs were evaluated for these pollution mitigation methods. METHODS: The effectiveness of cactus pads as a bio-flocculant and 30% FeCl3 for surfactant and phenol removal were studied using a jar test. The study was conducted on vegetable oil refinery wastewater from a refinery company in Casablanca, Morocco. RESULTS: The pollution load in wastewater varied widely from day to day. We evaluated the effect of cactus juice and 30% FeCl3 on high and low pollution loads. Opuntia pads showed a favorable potential for the treatment of low pollution load wastewater, with 78% and 90% of surfactant and phenol removed, respectively. However, the removal of high pollution load was less effective (42% and 41% removal of surfactant and phenol, respectively). The turbidity of low and high pollution load was reduced by 98.85% and 86%, respectively. The results demonstrate that 30% FeCl3 can effectively treat both low and high pollution loads (90% and 89% phenol removal, respectively, and 90% and 70% surfactant removal, respectively (optimal concentration 1.48 g/l). The turbidity was reduced by over 96% for both high and low pollutants. CONCLUSIONS: The results of the present study indicate that cactus as a natural flocculant and reject rich in FeCl3 could be effectively used for the low-cost effective treatment of crude vegetable oil refinery rejects. COMPETING INTERESTS: The authors declare no competing financial interests.

"On Water" Palladium Catalyzed Direct Arylation of 1H-Indazole and 1H-7-Azaindazole.

The C3 direct arylation of 1H-indazole and 1H-7-azaindazole has been a significant challenge due to the lack of the reactivity at this position. In this paper, we describe a mild and an efficient synthesis of new series of C3-aryled 1H-indazoles and C3-aryled 1H-7-azaindazoles via a C3 direct arylation using water as solvent. On water, PPh3 was effective as a ligand along with a lower charge of the catalyst Pd(OAc)2 (5 mol%) at 100 °C, leading to C3-aryled 1H-indazoles or C3-aryled 1H-7-azaindazoles in moderate to good yields.

Efficient Access to 3,5-Disubstituted 7-(Trifluoromethyl)pyrazolo[1,5-a]pyrimidines Involving SNAr and Suzuki Cross-Coupling Reactions.

An efficient and original synthesis of various 3,5-disubstituted 7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidines is reported. A library of compounds diversely substituted in C-3 and C-5 positions was easily prepared from a common starting material, 3-bromo-7-(trifluoromethyl)pyrazolo[1,5-a]pyrimidin-5-one. In C-5 position, a SNAr type reaction was achieved by first activating the C-O bond of the lactam function with PyBroP (Bromotripyrrolidinophosphonium hexafluorophosphate), followed by the addition of amine or thiol giving monosubstituted derivatives, whereas in C-3 position, arylation was performed via Suzuki-Miyaura cross-coupling using the commercially available aromatic and heteroaromatic boronic acids. Moreover, trifluoromethylated analogues of potent Pim1 kinase inhibitors were designed following our concise synthetic methodology.

Synthesis and Biological Evaluation of New Naphthoquinones Derivatives.

New substituted 1,4-naphthoquinones have been prepared in good overall yields through the naphthol route. The cytotoxicity of these compounds was tested in vitro on MCF-7 breast tumor cells. The most active compound 14 displayed an IC50 of 15µM. OBJECTIVE: To investigate the cytotoxicity of new naphthoquinones derivatives on MCF-7 cells. METHODS: Synthesis of new naphtoquinones derivatives and in vitro evaluation of their cytotoxicity on MCF-7 cells (rezasurin cell-based assay). RESULTS: Starting from Ethyl 4-hydroxy-6,7-dimethoxy-2-naphthoate, four naphthoquinones were prepared and exhibited substantial cytotoxicity against MCF-7 cells. CONCLUSION: Preliminary studies of the structure-activity relationship have shown the influence of the structural parameters and, in particular, the nature of the naphthoquinone side chain.

Unusual rearrangement of imidazo[1,5-a]imidazoles and imidazo[1,2-b]pyrazoles into imidazo[1,5-a]pyrimidines and pyrazolo[1,5-a]pyrimidines.

A multicomponent reaction giving easy and cheap access to a variety of bicyclic 5,5-fused hetero-rings has been developed. Then, an usual rearrangement of imidazo[1,5-a]imidazoles or imidazo[1,2-b]pyrazoles leading to bi-heterocyclic imidazo- and pyrazolo[1,5-a]pyrimidines in the presence of a specific amount of I2 in THF at room temperature has been achieved. This new method enables the hitherto unreported synthesis of functionalized imidazo- and pyrazolo[1,5-a]pyrimidines.

Regioselective Synthesis of New 2,4-(Het)aryl-3H-pyrido[1',2':1,5]pyrazolo[4,3-d]pyrimidines Involving Palladium-Catalyzed Cross-Coupling Reactions.

The design of some novel di-(het)arylated-3H-pyrido[1',2':1,5]pyrazolo[4,3-d]pyrimidine derivatives is reported. The series was developed from 1-aminopyridinium iodide, which afforded the key intermediate bearing two thiomethyl and amide functions, each of them useful for palladium catalyzed cross coupling reactions by alkyl sulfur release and C-O activation, respectively. The two regioselective and successive cross-coupling reactions were first carried out in C-4 by in situ C-O activation and next in C-2 by a methylsulfur release. Process optimization furnished conditions leading to products in high yields. The scope and limitations of the methodologies were evaluated and the final compounds characterized.