Synthesis Of Carbazoles Research Articles

Palladium(0)‐catalyzed Synthesis of Indoles and Carbazoles from o‐ Alkenyl (Alkyl) Anilines via C–H Amination Cyclization

Various indoles and carbazoles were synthesized from o‐alkenyl anilines and o‐aryl anilines by the β‐C(sp2)‐H bond amination cyclization without any oxidants or hydrogen acceptors. Likewise, employing o‐alkyl anilines as substrates, indole products are also obtained by the β‐C(sp3)‐H bond amination cyclization, and dehydrogenation. In this cross‐dehydrogenative coupling, many different functional groups are tolerated, and hydrogen gas is the only by‐product, thereby providing an intrinsically waste‐free approach for the synthesis of indoles and carbazoles.

Chemodivergent Synthesis of Polycyclic Aromatic Diarylamines and Carbazoles by Thermal/Photochemical Process-Controlled Dephosphinylative Functionalizations of Amino(phosphinyl)arenes.

A chemodivergent synthesis of polycyclic aromatic diarylamines and carbazoles was established by employing thermally or photochemically controlled processes using KOtBu/1,10-phenanthroline. The synthetic processes involved the dephosphinylation of 9-amino-10-(phosphinyl)phenanthrenes, which were obtained through a regioselective palladium-catalyzed direct [4 + 2] benzannulation of phosphinyl ynamines with 2-iodobiphenyls. When the dephosphinylation was conducted under heating conditions (∼100 °C), it proceeded to yield 9-aminophenanthrene. However, when the reaction was performed under the illumination of purple light (LEDs, λmax = ca. 390 nm), KOtBu/1,10-phenanthroline promoted single-electron-transfer-triggered dephosphinylation followed by cyclization, producing the corresponding π-expanded carbazoles. We successfully synthesized a highly π-expanded dicarbazole through a dual dephosphinylative cyclization. Additionally, we present the optical properties of a series of amino compounds produced through the dephosphinylative processes.

Ionic liquid Mediated Pd-catalyzed sonochemistry for facile synthesis of carbazoles: Molecular Modelling and antimicrobial studies

Herein we have described the Pd-catalyzed sonochemistry driven by [BMIM]-IL as re-useable solvent to synthesize various carbazole scaffolds from 2,2′-dibromodiphenyl. Diverse primary amines were utilised as coupling partners in the presence of [PAIM][NTf2], which exhibits an impactful promoter in the IL medium, thereby avoiding the need for hazardous VOC's. The recyclability of ionic liquids highlights the green approach of the reaction. Further, the synthesized carbazole scaffolds were assessed for antimicrobial activity. Compounds 3e and 3g are found to be highly active. The most probable binding sites for these scaffolds were screened through a computer-simulated docking method with targeted protein.

Synthesis of N-acyl carbazoles, phenoxazines and acridines from cyclic diaryliodonium salts.

N-Acyl carbazoles can be efficiently produced through a single-step process using amides and cyclic diaryliodonium triflates. This convenient reaction is facilitated by copper iodide in p-xylene, using the commonly found activating ligand diglyme. We have tested this method with a wide range of amides and iodonium triflates, proving its versatility with numerous substrates. Beyond carbazoles, we also produced a variety of other N-heterocycles, such as acridines, phenoxazines, or phenazines, showcasing the robustness of our technique. In a broader sense, this new method creates two C-N bonds simultaneously based on a mono-halogenated starting material, thus allowing heterocycle formation with diminished halogen waste.

Synthesis of biaryl-based carbazoles via C-H functionalization and exploration of their anticancer activities.

The synthesis of a library of new biaryl-based carbazoles via bidentate directing group-assisted C-H functionalization and preliminary screening of the anticancer properties of biaryl-based carbazoles is reported. While various classes of modified carbazoles are known for their applications in materials and medicinal chemistry, to our knowledge, the biological activities of designed biaryl-based carbazoles have been rarely known. Given the prominence of carbazoles in research in medicinal chemistry, we envisioned the scope for new scaffolds of carbazole-based biaryl structures. We screened the synthesized biaryl-based carbazoles for their anticancer properties against various cancer cell lines such as HeLa (cervical cancer), HCT116 (colon cancer), MDA-MB-231 and MDA-MB-468 (breast cancer). In addition, the hits were also tested in the human embryonic kidney cell line HEK293T to assess their impact on the viability of normal human cells in the presence of these compounds. In this preliminary study, we identified some of the biaryl-based carbazoles as lead compounds with anticancer activities.

A stable Copper-Modified silica microsphere catalyst for the synthesis of N-substituted carbazoles and organosilanes

Carbenes are key precursors for various transformations and are applied broadly in the synthesis of complex molecules and drug. Typically, such transformations require expensive metal and complex ligands, leading to a vigorous reaction system and trace metal residues. Herein, we report copper-modified silica microspheres (SM-b) as heterogeneous catalyst in the insertion reaction of diazo compounds with carbazole and silanes. Under this strategy, the optimal SM-b catalyst can prevent the reaction from being too vigorous and can be reused in continuous reactions. Furthermore, gram-scale and catalyst recycling reactions have been proven as the potential industrial applications of the SM-b catalysts. Inductively coupled plasma analysis revealed a residual copper content of only 6.25 ppm in the reaction solution and no detectable copper in the final product, indicating that the residual metal content of the product is far below the FDA-imposed limit of metal impurities.

Synthesis of carbazole–chalcone bis-oxime esters (CCBOEs) as blue light photoinitiators of polymerization

In this work, a series of bis-oxime esters, CCBOEswere designed as Type I photoinitiators for photopolymerization experiments done under low light intensities

A Facile One Pot Synthesis and Anticorrosion Potential of Carbazole Linked Quinoline Moiety

A facile and efficient one pot synthesis has been developed for the preparation of quinoline-substituted carbazoles 3-(4-carboxyquinolin-2-yl)-9-methyl-9H-carbazole (Cbz-QCA) and 3-(4-chloroquinolin-2-yl)-9-methyl-9H-carbazole (Cbz-ClQ) by treating 3-acetyl-9-methyl-9H-carbazole (3Ac-Cbz), with isatin under Pfitzinger reaction conditions and utilizing anthranilic acid in the presence of POCl3 through the modified Niementowski method, respectively. The synthesized compounds have been comprehensively characterized through spectral data. The effect of 3Ac-Cbz (1), Cbz-QCA (2) and Cbz-ClQ (3) were assessed as a steel corrosion inhibitor in molar hydrochloric acid using weight loss, potentiodynamic polarization, and electrochemical methods. The inhibitory effect rises with tested inhibitor concentration, reaching above 84% at higher concentrations of all tested inhibitors. These results indicated that tested inhibitors have a good corrosion inhibition. An increase in the inhibitor’s concentration leads to a higher percentage of inhibition efficiency, driven by the adsorption of inhibitor molecules onto the metal surface. Results from scanner electron microscopy (SEM) support the experimental inhibition tests have yielded successful outcomes and validate the adsorption process.

Synthesis, electropolymerization, and optoelectronic properties of carbazole containing imidazolium based ionic liquid

Herein, we report a prominent initial step toward the rational design of a carbazole-based ionic liquid. Firstly, the novel ionic liquid-based monomer of 1,3-bis[6-(9 H-carbazol-9-yl)-1H-imidazol-3-ium bromide] (coded as M4) salt has been synthesized 9{[6-(1 H-imidazol-1-yl) hexyl]-9 H-carbazole} which was prepared by the addition reaction of imidazole and N-(6-bromohexyl)carbazole, proceeded by connecting N-(6-bromohexyl) carbazole as precursor compound. The structural properties of the M4 have been determined by 1H NMR, 13C NMR, FT-IR, and MS spectral data. The corresponding polymer film (P4) has been synthesized electrochemically on the ITO electrode. The redox behaviors of the resulting polymer have been investigated in detail via cyclic voltammetry and spectroelectrochemistry techniques. The conducting polymer film has exhibited a multi-electrochromic behavior with color changes from transparent, to greenish-yellow and then to blue-green. Moreover, the polymer film has exhibited satisfactory optical contrast, high coloration efficiency, and fast switching time, which made them potential candidates in high-tech applications.

Iodine-Catalyzed Regioselective Synthesis of Diphenyl-Substituted Carbazoles via [4 + 2] Annulation of β-Formyl Ketones with Indoles.

The [4 + 2] annulation of β-formyl ketones with an indole has been developed for the regioselective synthesis of diphenyl-substituted carbazoles in the presence of a catalytic amount of iodine. The 1,4-dicarbonyl compound containing a phenyl group at the α-position of an aldehyde group reacts more readily with indoles to form carbazole derivatives. Using this method, a variety of carbazole derivatives can be readily accessed under mild reaction conditions.

Catalyst- and Substrate-Controlled Regiodivergent Synthesis of Carbazoles through Gold-Catalyzed Cyclizations of Indole-Functionalized Alkynols.

A wide variety of regioselectively substituted carbazole derivatives can be synthesized by the gold-catalyzed cyclization of alkynols bearing an indol-3-yl and an additional group at the homopropargylic positions. The regioselectivity of the process can be controlled by both the oxidation state of the gold catalyst and the electronic nature of the substituents of the alkynol moiety. The 1,2-alkyl migration in the spiroindoleninium intermediate, generated after indole attack to the activated alkyne, is favored with gold(I) complexes and for electron-rich aromatic substituents at the homopropargylic position, whereas the 1,2-alkenyl shift is preferred when using gold(III) salts and for alkyl or non-electron-rich aromatic groups.

Pd‐Catalyzed Decarboxylative Cross‐Coupling of N‐Aryl Anthranilic Acids to Access Carbazoles: Gram Scale Total Synthesis of Anti‐ Cancer Drug Ellipticine

AbstractAn efficient and scalable Pd‐catalyzed decarboxylative cross‐coupling strategy for the synthesis of carbazoles has been developed by using N‐aryl anthranilic acids. By employing a well‐designed catalytic system, this protocol access diverse carbazole derivatives via a C−C bond‐formation in one‐pot. The substituted carbazoles were obtained in good to excellent yields with high functional‐group tolerance. We have also demonstrated the gram‐scale synthesis of the anti‐cancer drug Ellipticine by utilizing this methodology. This concise and scalable total synthesis of ellipticine exemplifies the efficiency of our methodology in producing this significant anti‐cancer compound.

Condition-Controlled Selective Synthesis of Pyranone-Tethered Indazoles or Carbazoles through the Cascade Reactions of N-Nitrosoanilines with Iodonium Ylides.

Presented herein is a condition-controlled selective synthesis of pyranone-tethered indazoles or carbazole derivatives via the cascade reactions of N-nitrosoanilines with iodonium ylides. Mechanistically, the formation of the former involves an unprecedented cascade process including nitroso group-directed C(sp2)-H bond alkylation of N-nitrosoaniline with iodonium ylide followed by intramolecular C-nucleophilic addition to the nitroso moiety, solvent-assisted cyclohexanedione ring opening, and intramolecular transesterification/annulation. On the contrary, the formation of the latter involves the initial alkylation followed by intramolecular annulation and denitrosation. These developed protocols feature easily controllable selectivity, mild reaction conditions, a clean and sustainable oxidant (air), and valuable products that are structurally diverse. In addition, the utility of the products was showcased by their facile and diverse transformations into synthetically and biologically interesting compounds.

Synthesis of 2-Formyl Carbazoles via Tandem Reaction of Indolyl Nitrones with 2-Methylidene Cyclic Carbonate.

The synthesis of functionalized carbazoles as privileged nitrogen heterocycles has emerged as a central topic in drug discovery and material science. We herein disclose the rhodium(III)-catalyzed cross-coupling reaction between indolyl nitrones and 2-methylidene cyclic carbonate as an allylating surrogate, resulting in the formation of C2-formylated carbazoles via tandem C-H allylation, [3 + 2] cycloaddition, aromatization, and benzylic oxidation. The synthetic utility of this protocol is highlighted by a variety of post-transformations of C2-formylated carbazoles.

Design, Synthesis and Biological Screening of Novel Carbazole Tethered Oxyethylamino Derivatives as Antimicrobial Agent

Abstract: Background: Carbazole is an important scaffold known to be associated with several biological activities including antimicrobial activities. Incorporation 4-oxothiazolidine moiety in carbazole moiety may lead to a new series of antimicrobials compounds. Aim: In this study, design and synthesis of novel carbazole tethered oxyethylamino was started with carbazole as basic pharmacophore and evaluated for antimicrobial activity. Materials and Methods: Molecular docking of carbazole derivatives was carried out by Schrödinger (Maestro 10.5v) active compound were Synthesized and screened for in vitro antimicrobial activity against Candida albicans and gram-positive and gram-negative bacterial strains such as Staphylococcus aureus, Bacillus subtilis, E. coli. MIC was calculated by standard agar tube dilution method. Results: All Compounds shown good antimicrobial activity at 25 (μg/ml) – 510 (μg/ml). The molecular docking studies demonstrated ligand protein interaction. Conclusion: carbazole represent novel set of lead for the designing of novel antimicrobial agents. Keywords: Molecular Docking, Carbazole, Oxyethylamino, Antimicrobial activity, Antifungal activity.

Synthesis and investigation of bis(phenyl)fluorene and carbazole appended dipodal Schiff base for fluorescence sensing towards Sn(II) ion and its regioselective polymerization

One-pot condensation reaction between 9,9-Bis(4-aminophenyl)fluorene and 9-Ethyl-9H-carbazole-3-carbaldehyde afforded a chemosensor ((N,N′)-4,4′-(9H-fluorene-9,9-diyl)bis(N-((9-ethyl-9H-carbazol-2-yl)methylene)aniline, SB) having Schiff base skeleton. The further step was the synthesis of the polymer (P-SB) via oxidative polycondesation reaction of SB. FT-IR, 1H NMR and 13C NMR instruments were used to characterize the functional groups on the monomer and polymer. Thermal stability and electrochemical features of SB and P-SB were characterized by thermogravimetric analysis-differential thermal analyses (TG-DTA) and cyclic voltammetry (CV), respectively. The glass transition and surface image of P-SB were determined from DSC and SEM measurements, respectively. UV–vis and photoluminescence spectroscopy (PL) allowed to determine the optical properties of SB and P-SB. The obtained polymer, which had the weight average molecular weight of 8400 Da identified by gel permeation chromatography (GPC), exhibited fluorescence property. The synthesized turn-on fluorogenic chemosensor SB showed high selectivity and sensitivity towards Sn2+ among the cations of Ag+, K+, Hg2+, Mn2+, Cd2+, Sn2+, Ca2+, Pb2+, Zn2+, Co2+, Ni2+, Cu2+, Fe3+, Al3+, Cr3+ and Cr6+. The fluorescence turn-on recognition process for the detection of Sn2+ was related to the restriction of CN isomerization, followed by inhibiting intramolecular charge transfer (ICT), with consequent chelation-enhanced fluorescence (CHEF) mechanism. The stoichiometry ratio of the analyte-sensor adduct in the solution was found to be 1:1 by Job's plot method concomitant with a dramatic increase in fluorescent signal at 471 nm and a marked color change from colorless to turquoise blue upon addition of Sn2+ ions. Limit of detection value for the formation of SB-Sn2+ chelation was calculated as 3.37 nM. No change in PL intensity of SB-Sn2+ chelation was observed in the company of other metal ions. Reversibility of the chemosensor in its binding towards Sn2+ was demonstrated in the presence of chelating agent EDTA. The synthesized SB could effectively detect Sn2+ ion as a fluorescent sensor.

Synthesis of Multifunctional Arylated Anilines and Amino‐dihydrophenanthrenes Through Arylacetonitriles Mediated Ring Transformation of 2H‐Pyran‐2‐ones/2‐oxo‐benzo[h]chromenes

AbstractWe are reporting a simple and efficient synthesis of highly functionalized aniline by the reaction of 2H‐pyran‐2‐ones and benzyl cyanide in presence of sodamide in dioxane under reflux conditions. Various 4‐sec.amino‐2H‐pyran‐2‐ones, 4‐methylsulfanyl‐2H‐pyran‐2‐ones and 2‐oxobenzo[h[chromones were used as a substrate. Further, synthetic application of obtained arylated aniline was carried out to afford multifunctional carbazoles (13). 2′′‐Bromo‐[1,1′ : 2′,1′′‐teraryl]‐3′‐amines (6) and 4‐(2‐bromoarylyl)‐9,10‐dihydrophenanthren‐3‐amines (11) was used to demonstrate the the synthesis of carbazoles. The structure of isolated product 11 d was ascertained by spectroscopic and single crystal X‐ray diffraction analyses. We have explained the role of nonpolar solvents in the synthesis of arylated aniline.

Synthesis of C4-Aminated Carbazoles and Their Derivatives via Pd/NBE Chemistry.

Carbazole, as one of the most important organic frameworks, has been used in optoelectronic materials and biochemistry. However, the synthesis of C4-substituted carbazole has always been an unsolved problem. This report describes the one-step synthesis of C4-aminated carbazoles and their derivatives through the series reaction of C-H amination and arylation. The substrate scope is wide. C4-Amino carbazoles substituted by C2, C6, C7, and C8 methyl groups, especially carbazole derivatives of fused rings, pyridine, and dibenzofuran, can be synthesized.

Trends in carbazole synthesis - an update (2013-2023).

The interest of scientists in the carbazole core has risen steadily over the last 30 years, particularly over the last decade given its presence in several active pharmaceutical ingredients, functional materials and a wide range of biologically active natural products. The continuous development of more efficient, more (regio-)selective and "greener" methodologies to access the carbazole core is thus imperative. This review compares and evaluates synthetic strategies towards the carbazole core that have been reported since 2013, with a focus on their applicability towards the total synthesis of carbazole-containing natural products.

One-Pot Synthesis of Carbazoles by a Domino Reaction Using Microwave Heating and Antiproliferative Activities of Constituents from Murraya Plants Against Cancer Stem Cells

One-Pot Synthesis of Carbazoles by a Domino Reaction Using Microwave Heating and Antiproliferative Activities of Constituents from Murraya Plants Against Cancer Stem Cells