This paper presents the synthesis and full characterization of two regioisomeric azo compounds, CC4 (ortho-substituted) and the unexpected CC5 (meta-substituted), of the diazotization of 4-aminoacetophenone and reaction with 1-(4-hydroxyphenyl)ethan-1-one. Their side-by-side analysis clarifies how ortho vs. meta topology controls structure and properties. In contrast to the traditional expectations of coupling at the ortho positions of activated phenols, the regioselective attack at the unexpected meta position, with a combined isolated yield of 90%, is observed in the formation of CC5. The structures were unambiguously verified by combined spectroscopic methods (FTIR, 1D NMR, 2D COSY/HSQC, LC/GC-MS) and confirmed by the DFT calculations at the B3LYP/6-31G(d,p) level with a high level of agreement between experimental and calculated data. Theoretical analysis indicates that CC5 has a narrower HOMO–LUMO gap and favorable excited-state descriptors (e.g., oscillator strength and calculated LHE >0.8 in several solvents), suggesting potential for light-harvesting applications; however, the DSSC/photosensitizer implication is presented as a computational prediction pending experimental photophysical/electrochemical validation. The two compounds also demonstrated DNA-binding ability, as supported by agarose gel electrophoresis and molecular docking, with the hydrazone tautomer of CC4 showing the highest predicted affinity. Quantitative spectroscopic titration of CC4 further supported DNA interaction through the determination of an apparent binding constant (Kb,app). These findings suggest that CC4 may be useful for concentration-responsive biosensing and DNA labeling applications, because it retains optical readability while exhibiting a measurable spectroscopic response upon DNA association. This paper not only explains the structural and electronic differences between ortho- and meta-coupled azo isomers but also highlights CC5 as a promising candidate for light-harvesting and biomolecular-interaction studies, based on the combined experimental characterization and theoretical descriptors.

Positional isomerism is often a problem with the structural assignment of azo-hydroxybenzaldehyde derivatives since ortho/para products may have overlapping vibrational and NMR spectra. The ortho (XAHO) and para (XAHP) isomers of a chloro‑substituted azo-hydroxybenzaldehyde were synthesized by a diazotization-coupling reaction, and the regioselectivity was optimized by the control of the aqueous basic medium in this work. A significant medium effect was observed: the mixed base NaOH/Na2CO3 provided 98 % para, which allowed the isolation of the para isomer in a cleaner manner. FT-IR (ATR), NMR, and DFT/TD-DFT calculations at the B3LYP/ 631G(d,p) level were used to establish the structural assignments, with orbital and molecular electrostatic potential (MEP) visualization. The calculations indicate that the para isomer is thermodynamically preferred (ΔG = -4.265 kcal mol⁻¹) and has a substantially higher dipole moment (5.249 D), indicating a more polarized electronic distribution. Good experiment-theory correlation was obtained, including near-quantitative reproduction of the para-aldehyde ν(C=O) band (Δν = 2 cm⁻¹) and low errors for the scaled GIAO ¹H shifts of the nonexchangeable protons (MAE = 0.132 ppm). The study therefore provides an effective handle for controlling ortho/para selectivity and a reliable structure-spectroscopy interpretation workflow for azohydroxybenzaldehyde derivatives. As an auxiliary in silico observation, both isomers were accommodated in docking to the epidermal growth factor receptor (EGFR) ATP-binding pocket, and XAHO was predicted to bind slightly better than XAHP. Auxiliary SwissADME screening suggested high GI absorption and acceptable druglikeness for both isomers, with only slight isomer-dependent variations in lipophilicity and solubility.

This paper presents the synthesis and full characterization of two regioisomeric azo compounds, CC4 (ortho-substituted) and the unexpected CC5 (meta-substituted), of the diazotization of 4-aminoacetophenone and reaction with 1-(4-hydroxyphenyl)ethan-1-one. Their side-by-side analysis clarifies how ortho vs. meta topology controls structure and properties. In contrast to the traditional expectations of coupling at the ortho positions of activated phenols, the regioselective attack at the unexpected meta position, with a combined isolated yield of 90%, is observed in the formation of CC5. The structures were unambiguously verified by combined spectroscopic methods (FTIR, 1D NMR, 2D COSY/HSQC, LC/GC-MS) and confirmed by the DFT calculations at the B3LYP/6-31G(d,p) level with a high level of agreement between experimental and calculated data. Theoretical analysis indicates that CC5 has a narrower HOMO–LUMO gap and favorable excited-state descriptors (e.g., oscillator strength and calculated LHE >0.8 in several solvents), suggesting potential for light-harvesting applications; however, the DSSC/photosensitizer implication is presented as a computational prediction pending experimental photophysical/electrochemical validation. The two compounds also demonstrated DNA-binding ability, as supported by agarose gel electrophoresis and molecular docking, with the hydrazone tautomer of CC4 showing the highest predicted affinity. Quantitative spectroscopic titration of CC4 further supported DNA interaction through the determination of an apparent binding constant (Kb,app). These findings suggest that CC4 may be useful for concentration-responsive biosensing and DNA labeling applications, because it retains optical readability while exhibiting a measurable spectroscopic response upon DNA association. This paper not only explains the structural and electronic differences between ortho- and meta-coupled azo isomers but also highlights CC5 as a promising candidate for light-harvesting and biomolecular-interaction studies, based on the combined experimental characterization and theoretical descriptors.

A succinct and efficient synthetic route to 8,9-dihydro-6H-pyrido[2,1-b]quinazolin-11(7H)-one is developed. The compound was synthesized by condensing piperidin-2-one with methyl 2-aminobenzoate in the presence of phosphorus oxychloride and then by a one-step intramolecular cyclization. The target heterocycle was obtained as a white crystalline solid with an 86% yield. The resulting product was well characterized by IR, ¹H NMR, ¹³C NMR, DEPT, COSY, HSQC, and HRMS spectroscopic methods, and the obtained data revealed a high level of consistency between experimental and theoretical findings. The complementary DFT and TD-DFT studies also confirmed the suggested molecular structure and identified important electronic characteristics, such as high intramolecular charge-transfer (ICT) character and significant stabilization energies, which confirmed the overall structural integrity and stability of the compound. TD-DFT computations revealed strong π → π* transitions with large oscillator strengths, which are associated with the exceptional light-harvesting efficiency (LHE = 0.4016) in dichloromethane (DCM). This strong optical performance highlights the possibility of the compound as an effective sensitizer in dye-sensitized solar cells (DSSCs), making it a promising candidate in the development of solar cells in the next generation. Molecular docking experiments have shown high binding affinities to the oncogenic (cancer-related) protein target 4XH6 and the Crimean-Congo haemorrhagic fever virus (CCHFV) glycoprotein 3PRP with calculated binding energies of -8.5 kcal/mol, respectively, indicating potential promise as a lead structure in anticancer and antiviral drug development. It is worth noting that CCHFV is a major health threat in the region, as pointed out by the World Health Organization.

This study reports the synthesis and characterizing of a novel azo-chalcone incorporating a dimethylamino-diazenylphenyl fragment, designed as a safer organic dye for DNA staining. Spectroscopic methods (IR, ¹H/¹³C NMR) confirmed the structure, while density functional theory (DFT) revealed its electronic properties, demonstrating comparable reactivity in gas and ethanol phases with enhanced electrophilicity in solution. Molecular docking identified minor groove binding to A-T-rich DNA regions (docking score:8.212 kcal/mol), supported by hydrogen bonds and van der Waals interactions. The compound adhered to Lipinski’s rule of five and exhibited favorable ADMET profiles, though risks of CYP inhibition and hepatotoxicity were noted. Hirshfeld surface analysis highlighted weak non-covalent interactions, while MEP mapping identified nucleophilic sites at carbonyl oxygen. This work advances chalcone-based dyes for DNA visualization, offering insights into structure-activity relationships and pharmacokinetic optimization for therapeutic applications.

A novel zinc-based metal–organic framework was successfully employed as a catalyst in the Claisen–Schmidt condensation reaction for the synthesis of azo-chalcone. The catalyst demonstrated excellent recyclability and maintained high activity after the reaction without loss of effectiveness. The synthetic protocol allows for simple product isolation, easy workup, and efficient purification, supporting potential scale-up for industrial applications. Quantum chemical calculations provided insights into the electronic and structural properties of the synthesized azo-chalcone. Molecular docking studies revealed strong binding affinity of the chalcone to Escherichia coli DNA gyrase, with a docking score of − 10.794 kcal/mol. Key interactions involved hydrogen bonding and van der Waals forces, particularly with the amino acid Asn46, which is critical in ATP hydrolysis inhibition. The compound also displayed favorable drug-like properties according to Lipinski’s rule and absorption, distribution, metabolism, elimination, and toxicity profiles.

Metal-organic frameworks (MOFs)-derived heterogeneous catalysis has gained significant attention for their catalytic efficacy and unique structural features, making them valuable in various organic syntheses by enhancing reaction efficiency, selectivity, and sustainability. MOFs are highly effective catalysts in organic synthesis due to their catalytically active sites, significant surface areas, tunable pore structures, and a wide range of chemical characteristics that enhance selectivity and accelerate reactions. This study introduces the application of a novel MOF (called UoZ-2) as a heterogeneous catalyst for synthesizing a novel azo-chalcone product through the Claisen-Schmidt condensation process. The UoZ-2 acid catalyst is esteemed for its many benefits, such as operating under mild conditions, achieving rapid reaction rates, facilitating straightforward recovery and isolation without diminishing catalytic efficiency after multiple uses, enabling easy product purification, and offering scalability and lower cost for industrial applications. Furthermore, azo-chalcone product synthesis under microwave irradiation conditions achieves a high yield, saving energy and time, which was compared with the traditional reflux method. Ultimately, these outcomes confirm the use of a friendly environmental method. Moreover, the reusable studies exhibited that the catalysts were found to be stable and reusable for up to three cycles without substantial loss of catalytic activity. The synthesized azo-chalcone was thoroughly characterized using spectroscopic techniques, and its biological potential was assessed through molecular docking studies with the HER2 protein. Computational studies, including density functional theory and ADMET analysis, further revealed the synthesized compound’s electronic properties and pharmacokinetic potential. The findings highlight the potential of UoZ-2 as an efficient and sustainable catalyst for the scalable synthesis of biologically relevant chalcones, offering an environmentally friendly alternative to traditional homogeneous catalytic systems.

Several novel Bis-Oxazepine and Bis-Benzoxazepine derivatives have been produced by condensation and cyclization processes over two effective practical stages. The first stage involved utilizing the Dean-Stark apparatus to create imine intermediates through the condensation reactions of 3-hydroxy benzaldehyde with various aromatic diamine substrates in the presence of glacial acetic acid as a catalyst. The second stage required treatment of bis-Schiff base intermediate with maleic- or phthalic anhydride in dry benzene to produce the desired Bis-Oxazepine and Bis-Benzoxazepine derivatives with 70-95% yields using microwave irradiation. The molecular docking of the produced chemicals was conducted against the progesterone receptor. The results indicate potential anticancer properties for three compounds, which show the most promising findings. These compounds obtained higher docking scores (ΔG −9.58, −9.28, and −9.11 kcal/mol), forming three hydrogen bonds with the target protein.

Over three major convenient steps, a series of some novel Bis-Schiff bases, and Bis 1, 3-thiazolidin-4-one derivatives have been synthesized: Firstly, the etherification process through the reaction of the 4-hydroxybenzaldehyde substrate with o-, m-, and p-chlorobenzylchlorides under mild circumstances. Secondly, the condensation reaction between 4-((chlorobenzyl) oxy) benzaldehyde compounds with a number of aromatic diamines in an acidic environment produces the required Bis-schiff intermediates. Finally, the practical cyclization step was finished by synthesizing the required Bis 1, 3-thiazolidin-4-one products with 79-97% yields through refluxing reaction in benzene with thioglycolic acid.

his work includes synthesis of the novel azo compound, which consists of diazotization of 3-nitroaniline followed by reaction with 4-hydroxybenzaldehyde in presence of sodium carbonate. The syanthesized azo compound was confirmed by characterization, using FT-IR, 1HNMR, 13CNMR and GC-MS spectra. The azo compound was screened for solvatochromism, Halochromism using UV-Vis spectrophotometer, and found that the azo compound exhibited low solvatochromic and good Halochromic properties. While the dying study (Dye-doped Polymer Films), Poly ethylene was found the best polymer dyed by azo compound and showed good absorbance in the UV region. All fabrics were dyed with a yellow color except the cotton exhibiting a light brown color.

This work is divided into two main parts. The first part involves the synthesis of new azo chalcone compounds through a two-step process. Initially, azo compounds are synthesized by diazotizing 3-nitroaniline, followed by a coupling reaction with 4-hydroxyacetophenone, which has a terminal ketone group. Subsequently, the resulting product undergoes a Claisen–Schmidt condensation reaction with various aromatic aldehyde substrates to produce new α, β-unsaturated ketones, known as azo chalcone compounds. The successful synthesis of these compounds is confirmed using Fourier-transform infrared spectroscopy, ¹H NMR, and ¹³C NMR spectral analyses. The second part of this study explores the theoretical biological activity of the synthesized compounds against severe acute respiratory syndrome coronavirus 2 through molecular docking studies. The results indicate potential antiviral properties for each compound, with compounds B5 and B8 exhibiting the most promising results. These compounds achieved higher docking scores (ΔG −6.235 kcal/mol and −5.832 kcal/mol, respectively) and each formed four hydrogen bonds with the target protein

Over three major convenient steps, a series of some novel Bis-Schiff bases, and Bis 1,3-thiazolidin-4-one derivatives have been synthesized: Firstly, the etherification process through the reaction of the 4-hydroxybenzaldehyde substrate with o-, m-, and p-chlorobenzylchlorides under mild circumstances. Secondly, the condensation reaction between 4-((chlorobenzyl)oxy)benzaldehyde compounds with a number of aromatic diamines in an acidic environment produces the required Bis-schiff intermediates. Finally, the practical cyclization step was finished by synthesizing the required Bis 1,3-thiazolidin-4-one products with 79-97% yields through refluxing reaction in benzene with thioglycolic acid.

The current assignment depicts the structure of recent quinoline derivatives. This method begins with the structure of imine derivatives through the condensation reaction of ethyl 2-aminobenzoate with various substituted aliphatic aldehydes and ketones in the existence of sodium hydroxide as a catalyst. While the second step includes the intra-cyclization process of the imine compounds in presence of a base like tertiary butoxide that resolute installs the hydroxyl-group on the bicyclic skeleton and aromatic amines. The molecular docking program Flare V4. 0 was applied to investigate the biological activities of divers produced compounds against E. coli bacteria. Spectral data support the compounds of each the recent outputs acquired during this assignment.

Several new bis-Schiff bases and bis 4-thiazolidinone derivatives were synthesized through condensation and cyclization processes over two effective practical steps. The initial step included the synthesis of imine derivatives by the condensation reaction of 2-hydroxy-1-naphthaldehyde with various aromatic diamine substrates in existence of glacial CH3COOH as a catalyst. The second step involved reaction between bis-Schiff base derivatives with thioglycolic acid in anhydrous benzene to produce the desired 4-thiazolidinones.

A series of new quinoline derivatives was synthesized involving two main steps. In the first step, imine derivatives were obtained through the condensation reaction of 2-aminobenzonitrile with different substituted aliphatic aldehyde and ketone substrates in the presence of sodium hydroxide as a catalyst. The intramolecular-cyclization of the imine derivatives in the presence of a base like tBuOK afforded new 4-aminpquinoline derivatives. The structures of all the new products were confirmed by spectral and analytical data.

Due to the largely and an efficient usage of Weinreb amides or N-methoxy-N-methylamides as are remarkable intermediate in the organic synthesis field, the recent review paper provides a considerable development literature survey on the Weinreb amides synthesis. The direct transformation of carboxylic acids,acid chlorides, and esters to aldehydes or ketones employing organometallic reagents do not lead in high yields, since the high reactivity of ketone intermediates toward the organometallic reagents. While, the conversion to the appropriate Weinreb Amides, followed by treatment with the organometallic regent, result the stable expected ketones as the stable initial adduct toward further reactions. Furthermore, Weinreb amides undergo nucleophilic addition and produce a unique and steady five-membered cyclic intermediate which protects the over-addition, leading to a serious transformation.

New Schiff base compounds have been prepared. Various aliphatic and aromatic ketones were condensed with naphthalene-1, 5-diamine to yield the desired Schiff bases. The structures of all the new products obtained in the present work are supported by spectral and analytical data (IR, NMR and Mass spectroscopy). Furthermore, the biological activity of Schiff Bases compounds was tested against two types of bacteria gram positive for the dye (Staphylococcus aureus) and gram-negative dye (E.Coli).

This review highlights recent multicomponent reactions improvement in the synthesis of pyrano[2,3- c]pyrazole derivatives in presence of different catalysts including sodium benzoate, CAN, AmberlystA21, L- or S-proline, CTACl, n-TiO2/H14[NaP5W30O110], SiO2TMG,Fe3O4, DMAP, MS 4Å, DABCO, NH4H2PO4/Al2O3,SnO2QDs, CAPB, BF3/MNPs, (Ni 0.5 Zn0.5Fe2O4@Hap-Cs2CO3), VB1, ZrO2 NPs,βCD,TUD, urea, NaBr, MMT-ZSA, piperidine, NMOAg2O, InCl3, PEG-400, NaF and SiO2. In this context, modern routes in the preparation and use of pyrano[2,3-c]pyrazole as a pioneer for the heterocyclic framework are based on three- or fourmulticomponent reaction of ethyl acetoacetate, hydrazine or phenylhydrazine, aromatic aldehyde and malononitrile substrates in presence of catalyst.

N-methoxy-N-methyl amides or Weinreb amides are worthy embranchment of amide group and their rich functional groups in organic synthesis become a strong else unfeasible conversion. Weinreb amides are produced as an intermediate product of the reaction of carboxylic acids, acid chloride or esters with organometallic reagents, which was first uncovered in 1981. The direct conversion of carboxylic acids or acid chlorides or esters to ketones or aldehydes using organometallic reagents do not lead in high yields, because the intermediate ketones are still highly reactive toward the organometallic reagent. However, after derivatization to the corresponding Weinreb amide, reaction with organometallics does give the desired ketones, as the initial adduct is stabilized and doesn't undergo further reactions. A nucleophilic addition to the Weinreb amides results in a unique and stable five-membered cyclic tetrahedral intermediate which protects the over-addition, leading to a selective conversion.

The present work describes the synthesis of new 1,5-naphthyridine derivatives. The procedure is based on the cross-coupling reaction of commercially available 2-iodo-1,5-naphthyridine with aromatic and heteroaromatic boronic acids through the Suzuki reaction. This process furnished the desired products in high yields. The structures of all the new products obtained in this work are supported by spectral and analytical data.

A novel and an efficient strategy of fused tricyclic quinoline heterocycle compounds from aliphatic amino carboxylic acid substrates was studied. The protocol here is proceed over main reaction processes including: cyclization, protection, amidine formation, further cyclization and finally coupling with boronic acid substrate through Suzuki reaction. These reactions afforded the corresponding products in high yields. Furthermore, all synthesized compounds were identified by spectral data.

The three-component free-radical carbo-alkenylation of electron-rich olefins has been studied, varying the substitution pattern in the alkene, in the radical precursor and in the final acceptor. New vinylsulfones were also prepared and their reactivity investigated. The scope and limitations of the process was established, and the reaction mech anism clarified using selected dienes as radical clocks. It was thus recognised that the reversible addition onto the olefin of the released sulfonyl group is an important event, which should not be overlooked when using such multicomponent carbo-alkenylation reactions.

facile and suitable method for the synthesis of different 1, 8-Naphthyridine derivatives is depicted. The procedure is based on the diazotization and triflation reactions of commercially available 1, 8-naphthyridine-2-amines followed by cross-coupling with aromatic and heteroaromatic boronic acids through Suzuki reaction. These processes reserved the required yields in high percentage. All synthesized compounds were identified by spectral data.

This review highlights the most recent syntheses of free radical reactions, which included numerous processes (photoredox catalysis freeradical reactions, free-radical cascade processes reactions, Minisci-type free radical alkylation reactions and metal-catalysis free radical reactions). A photoredox-catalyzed C–H functioning of aromatic heterocyclic utilizing an assortment of various, alkyltrifluoroborates has been mentioned. Utilizing organo-photocatalyst and a moderate oxidant, conditions malleable for functionalizing complex aromatic heterocyclics are outlined to prepare a oriental agent for late-stage derivatization. Radical alkylations of aromatic heterocyclic (Minisci reactions) appear a more direct functionalization of particular, C–H bonds. For the ground mentioned above, alkylation designing using radical have recently risen to significance for the late-stage functionalization of aromatic heterocyclic framework. Therefore, this issue is the primary point of the present survey, which thinks about work from the most recent five years. The work is ordered by the key procedures associated with the synthesis of free-radical reactions, planning to give researchers a simple comprehension of this free radical–reactions-based science and to give bits of knowledge to provide insights for further investigations.

This review highlights recent improvement in trifluoromethylene functionalization processes with CF3 reagents, includes: Togni’s, Umemoto’s, CF3SO2Cl, CF3I, Yagupol’skii-Umemoto, TMSCF3, Langlois (CF3SO2Na) and clarifies the several designing to result the corresponding trifluoromethylated products. In this article, the selective trifluoromethylation reactions with Togni’s reagents and their analogs are detailed, which work transition metals or photoactivated Ru or Ir catalysts as single electron giver to yield CF3 radical intermediate species. This issue is to introduce a draft of diverse reports, presenting the modern reaction collect and mechanics produced during the past five years. This task is demanded by the key protocol connected with the trifluoromethylation reactions, designing to sustain researchers a straight forward understanding of such reactions and to award information for further implements.

This review highlights recent advances in catalytic enantioselective halofunctionalization of alkenes and explains the various planning to bring about regio- or stereoselective transformations. Halocyclization of olefinic substrates is an encouraging organization in creating O- and N-heterocyclic compounds, which additionally connotes the advancement of their asymmetric variations. The initiation of alkenes and their ensuing functionalization is an as often as possible utilized system in synthetic chemistry. The degree and difficulties of intra- and inter-molecular reaction variations have well talked about. The point is to give an outline of different reports, featuring the new reaction composes and techniques created amid the previous 5 years.

In recent years, an interest in the synthesis of crown ether Schiff bases and their complexes has been increased, due to the significance and broadly the uses of these compounds in various fields. The present review paper outline extensive recent advances literature survey on the crown ether including azomethine group and their complexes with the tough and easy granter atoms, has been reconsidered. Emphasis has been done on element complexation with crown ether holding Schiff bases to enable the researchers to procure valuable information of the chelating activity of crown ether containing azomethine group and their enforcement.

A convenient procedure for the preparation of variously substituted quinolines is described. The new method is based on Mitsunobu reaction of aromatic amines with phosphonium yields. Facile onepot synthesis of quinolones derivatives involving an Aza-Wittig reaction of aryliminophosphorane with substituted aldehydes and cyclization of intermediates was achieved under basic conditions.

An efficient one-pot synthesis of imidazo-dipyrimidine-4,9(3H)-diones and pyrimidopyrazinopyrimidine-4,10(3H,6H)-diones was developed using novel Vilsmeier reagent. A mixture of 5-ethyl-5-methyl-2,4-imidazolidine-dione or 2,5-piperazine-dione and substituted amino esters underwent cyclization at ambient temperature in dry dichloromethane to afford the desired products. The structures of all the new products obtained in the present work were supported by spectral and analytical data (infrared, nuclear magnetic resonance, and mass spectroscopy).

The reaction of ethyl 2-aminobenzoate with different substituted amide compounds led to cyclization through Vilsmeier intermediate in dry dichloromethane and ambient temperature, affording the 4(3H)-quinazolinone derivatives with higher yields. The structures of all the new products obtained in this work are supported by spectral and analytical data (infrared, nuclear magnetic resonance, and mass spectroscopy).

The addition of electrophilic precursors such as benzylketone and weinreb amide xanthate across the double bond of unactivated olefins provides access to the corresponding three-component adducts in good to the excellent yields under mild conditions.

Addition of functionalized carbon fragments across the olefinic π-system through a freeradical carbo-oximation process offers a straightforward access to valuable intermediatesfor organic synthesis. For this purpose, we designed a new protectedsulfonyl oxime, which enable rapid radical addition with high yields under mild conditions.

Addition of functionalized carbon fragments across the olefinic π-system through a freeradical carbo-oximation process offers a straightforward access to valuable intermediatesfor organic synthesis. For this purpose, we designed a new protectedsulfonyl oxime, which enable rapid radical addition with high yields under mild conditions.

A convenient procedure for the preparation of various naphthyridine constructions is described. The method is based on the Vilsmeier, cyclization and Suzuki reactions of piperidinone with substituted aniline. The reactions provided the desired fused tricyclic heterocycles products in high yields.

The first total synthesis of eucophylline was reported in 10 steps and 10% overall yield. The naphthyridine core of eucophylline was prepared through the coupling between a strained azabicyclo[3.3.1]nonan-2-one and a trisubstituted benzonitrile, followed by a cyclization of the corresponding amidine. This coupling reaction was shown to proceed through a stable bicyclic chloroenamine intermediate. The azabicyclo[3.3.1]nonan-2-one skeleton was in turn accessible through a straightforward sequence including a free-radical three-component olefin carbo-oximation as a key step

The aim of this work was to develop new radical multi-component processes and their application in organic synthesis. Carbo-alkenylation processes were thus performed with new radical precursors, different olefins, in the presence of Zdiphenylsulfonylethylene as a terminal acceptor. Reaction conditions have also been optimized, including the diphenylsulfonylhydrazine as a radical initiator under U.V. irradiation, and substitute to the costly DTBHN. Tin-free conditions were also screened with the goal of replacing (Bu3Sn)2 with silyl radicals. Tris(trimethylsilyl)silylthiopropene was tested with success as a radical chain carrier. After this methodology studies, we developed a strategy toward the synthesis of Eucophylline, an alcaloid isolated from Leuconotis griffithii, which tetracyclic skeleton was elaborated based on a carbooximation of olefin. This multicomponent process, followed by a reduction of the oxime function and a lactamization offered a fast access to the bicyclo[3.3.1]lactam, a keyintermediate in the synthesis. A Friedländer-type reaction between this lactam and an ortho-aminobenzonitrile allowed an access to the Eucophylline tetrahydrobenzo[1,8]naphthyridine skeleton. The synthesis of the model compound was finally completed with the introduction of the vinylic substituent through a Heck coupling.