Synthesis Of Carbazoles Research Articles

Synthesis of New Carbazole–Thiazole Analogues and Evaluating their Anticancer Activity

Medicinal research has focused on the discovery and progress of anticancer drugs. Carbazole and thiazole are organic heterocyclic compounds that are the building blocks for synthetic and natural pharmaceutical compounds. Thus, this research article involves the synthesis of nine carbazole linked thiazolidinone derivatives from the Knoevenagel reaction of 9-ethylcarbazole-3-carbaldehyde with several thiazolidine-5-one and thiazolin-4-one derivatives. The structures of these compounds were confirmed by spectroscopic tools such as IR, 1H and 13C NMR, and mass spectrometry. The MTT assay, using Cisplatin as a reference drug, was used to test the cytotoxicity of the synthesized carbazole-thiazole analogous against three different cell lines: breast cancer (MCF-7), hepatocellular carcinoma (HepG-2), and colon carcinoma (HCT-116). The 3b and 5c molecules were the most effective antitumor drugs against the three cell lines. Compound 3b has IC50 values of (0.0304 ± 0.001, 0.058 ± 0.002 and 0.047 ± 0.002 µM) for HepG-2, MCF-7, and HCT-116, respectively. When examined on HepG-2, MCF-7, and HCT-116 cell lines, the IC50 values revealed by component 5c were (0.048 ± 0.002, 0.086 ± 0.0025 and 0.06 ± 0.007 µM), respectively.

“Back‐to‐Front” Indole and Carbazole Synthesis from N,N‐Bis‐(2‐bromoallyl)amines by Combining Carbolithiation Reactions with Gold‐Catalysis

AbstractThe combination of organolithium chemistry with gold catalysis has enabled the development of a synthetic strategy for accessing polysubstituted indoles and carbazoles from readily available starting materials. This method is based on a “back‐to‐front” approach from ketopyrroles, generated by intramolecular carbolithiation of N,N‐bis‐(2‐lithioallyl)amines that evolve into 3,4‐bis(lithiomethyl)dihydropyrrole intermediates capable of reacting with carboxylic esters and Weinreb amides. These ketopyrroles have demonstrated to be excellent precursors of mono or bis(alkynols)pyrroles that, under gold‐catalysis, experience a benzannulation reaction providing access to regioselectively substituted indoles or carbazoles.magnified image

Palladium‐Catalyzed Sequential C−H Activation/Amination of 2‐Iodobiphenyls with Benzoisoxazoles for Synthesis of Carbazoles

AbstractA coupling reaction of 2‐iodobiphenyl with benzoisoxazole under the cooperative catalysis of Pd(CH3CN)2Cl2 and P(4‐F−Ph)3 is disclosed. The reaction proceeds via intramolecular C−H activation/N−O cleavage/migratory insertion sequence to give an array of N‐arylcarbazoles with an aldehyde or a ketone. The employment of benzoisoxazoles as an amination agent obviates the need for stoichiometric amount of oxidants.magnified image

Palladium‐Catalyzed Synthesis of Carbazoles by Perester

AbstractAn intramolecular C−H amination for the synthesis of carbazoles with a Pd(II)/TBPB system has been developed. This catalytic amination process forms the carbazole products in good to excellent yields. It is noteworthy that this method implied the advantages of the catalytic mode involving perester with transition metal catalyst in the activation of inert C−H bonds. In addition, the transformation performs well using water as solvent.magnified image

Synthesis of Diarylamines and Methylcarbazoles and Formal Total Synthesis of Alkaloids Ellipticine and Olivacine

AbstractNew and efficient strategies for the conversion of 4‐oxazolin‐2‐ones into 1‐methyl and 1,4‐dimethyl 3‐formylcarbazoles are herein described. Highly convergent cascade and one‐pot processes afforded the corresponding diarylamines, as in situ formed synthetic intermediates or final products in high overall yields. Special attention was given to the synthesis of methylated carbazoles by reacting 4,5‐dimethyl‐4‐oxazolin‐2‐ones with enones under microwave irradiation. The carbazole scaffold was provided by the palladium(II)‐catalyzed double C−H activation to generate oxidative cyclization of diarylamines. This methodology allowed for formal total syntheses of four naturally occurring pyrido[4,3‐b]carbazole alkaloids ellipticine, 9‐methoxyellipticine, olivacine, and 9‐methoxyolivacine.

A Chemo- and Regioselective Tandem [3 + 2]Heteroannulation Strategy for Carbazole Synthesis: Combining Two Mechanistically Distinct Bond-Forming Processes.

A modular approach to prepare tri- and tetracyclic carbazoles by a sequential [3 + 2]heteroannulation is described. First, optimization of Pd-catalyzed Buchwald–Hartwig amination followed by C/N-arylation in a one-pot process is established. Second, mechanistic analyses identified the origins of chemo- and regioselective sequential control of both bond-forming steps. Finally, the substrate scope is demonstrated by the preparation of a range of tri- and tetracyclic carbazoles, including expedient access to several natural products and anti-cancer agents.

Palladium-Catalyzed Benzannulations of 1-(Indol-2-yl)but-3-yn-1-ols: Easy Access to Functionalized Carbazoles.

An atom-economical direct synthesis of carbazoles having aryl and aryl ketone groups has been achieved through Pd(II)-catalyzed cascade reactions between 1-(indol-2-yl)but-3-yn-1-ols and aldehydes. The reaction proceeds through alkyne-carbonyl metathesis, an uncommon pathway using palladium catalysts, and constitutes a fast intermolecular assembly through four carbon-carbon bond formations in one pot. Absence of the aldehyde substrate resulted in the formation of C4-aryl-substituted carbazoles. The reaction is amenable to the synthesis of biscarbazole derivatives.

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Diarylation of N- and O-nucleophiles through a metal-free cascade reaction

Cu(i)-catalyzed cross-coupling of primary amines with 2,2'-dibromo-1,1'-biphenyl for the synthesis of polysubstituted carbazole.

A Cu(i)-catalyzed cross-coupling of primary amines with 2,2′-dibromo-1,1′-biphenyl for the synthesis of polysubstituted carbazole has been achieved. This protocol provides an efficient strategy for the synthesis of carbazole using cheap copper catalysts with diamine ligand, and it provides convenient access to a series of carbazole derivatives in moderate yields.

Synthesis of indoles and carbazoles from a lignin model compound α-hydroxyacetophenone

We describe a strategy for the synthesis of indoles or carbazoles in a green system using the oxidized lignin model compound α-hydroxyacetophenone as the starting material.

Modular Synthesis of Carbazole-Substituted Phthalimides as Potential Photocatalysts

AbstractThe modular synthesis of carbazole functionalized phthalimides (PIs) and their applicability as catalyst in selected photocatalytic transformations are reported. The developed synthetic approach provides high variability of phthalimide considering that the synthesis of the phthalimide core can be easily performed. Starting from fluorophthalic acid anhydrides, the corresponding fluorophthalimides were prepared with various amines, and the fluoro function ensured the introduction of carbazoles into the phthalimide framework through aromatic nucleophilic substitution. Besides the synthetic developments, some of the carbazolyl phthalimides were tested in four different photocatalytic transformations, which showed attractive and comparable activity to the known 4-CzIPN and noble metal complexes.

Benzotriazoles and Triazoloquinones: Rearrangements to Carbazoles, Benzazirines, Azepinediones, and Fulvenimines.

The denitrogenative rearrangements of several types of benzotriazoles were investigated by DFT (B3LYP/6-311G(d,p)) and CASPT2(10,10)sp/6-311G(d,p) calculations. The Graebe-Ullmann synthesis of carbazoles 18 by pyrolysis or photolysis of 1-arylbenzotriazoles 14 proceeds without the involvement of benzazirines and without Wolff-type ring contraction to fulvenimines. However, 1-aryltetrahydrobenzotriazoles undergo both cyclization to tetrahydrocarbazole and ring contraction. Triazoloquinones like 34 undergo predominant ring contraction to aminofulvenediones like 38 and also ring expansion to azepinediones like 40 and cyclization to N-arylbenzaziridinediones 39, whereas carbazolediones are not formed. Denitrogenation of 1-methylbenzotriazole 64 results in a facile 1,2-H shift with formation of N-phenylmethanimine 67. 1-Cyanobenzotriazole 71 undergoes destructive pyrolysis with charring, and the calculations predict the occurrence of several low-activation energy reaction pathways.

Synthesis of Carbazoles and Dihydrocarbazoles by a Divergent Cascade Reaction of Donor-Acceptor Cyclopropanes.

An alkylation/olefination cascade of indolecarboxaldehydes and phosphonate-functionalized donor–acceptor cyclopropanes affords functionalized dihydrocarbazoles and cyclohepta[cd]indoles in formal (3 + 3) and (4 + 3) cycloadditions. A minor modification to the reaction conditions also allows access to the fully aromatic heterocyclic scaffolds by thermal loss of an electron-rich aryl moiety.

A New and Effective One‐Pot Synthesis of Polysubstituted Carbazoles Starting from β‐Nitro‐β,γ‐Unsaturated‐Ketones and Indoles

AbstractHerein, we report a new one‐pot synthesis of polysubstituted carbazoles starting from β‐nitro‐β,γ‐unsaturated‐ketones and indoles. The process is based on a Friedel‐Crafts reaction of indoles to nitroolefins supported by 2,2,2‐trifluoroethanol (TFE) followed by an acidic‐promoted and microwave‐assisted intramolecular cyclization, that involves the elimination of both nitrous acid and water molecules. Products were obtained in satisfactory to good overall yields (55–78%).

Convenient One-Pot Synthesis of 9H-Carbazoles by Microwave Irradiation Employing a Green Palladium-Based Nanocatalyst

AbstractAn efficient palladium-catalyzed tandem reaction for the one-pot synthesis of 9H-carbazoles under microwave irradiation is developed. This approach involves a sequential Buchwald–Hartwig amination and a direct arylation from affordable and inexpensive anilines and 1,2-dihaloarenes. For the development of this purpose, a novel and magnetically recoverable palladium nanocatalyst supported on a green biochar under ligand-free conditions is used. Compared to other existing palladium-based protocols, the present synthetic methodology shows a drastic reduction in reaction times and excellent compatibility with different functional groups allowing to obtain a small library of 9H-carbazoles in high yields and with good regioselectivity. This procedure represents the first example in the direct synthesis of carbazoles using a heterogeneous palladium nanocatalyst from commercial precursors. To examine the application of this protocol, a direct and scalable synthesis of the bioactive carbazole alkaloid clausenalene from commercially available starting materials is described.

Effect of carbazole coating on TiO2 nanoparticles as a photosensitizer and MWCNTs on the performance of epoxy composites

Over a short period of time, electronic assemblies have been dramatically developed with smaller size and lighter weight and 3D printing plays a crucial role in their future production. However, it is difficult to develop epoxy resins and other thermoset resins for this process because of the polymer's liquid state during processing. This work uses a UV curing technique for making flexible epoxy/multi-walled carbon nanotubes (MWCNTs) composites that are suitable for future 3D printing applications. The synthesized carbazole-coated TiO 2 nanoparticles, used as a photosensitizer, were characterized by their photoabsorbance, morphology, and surface property before use. The results indicated that the TiO 2 nanoparticles coated with 75 wt% carbazole were appropriate for UV-cured flexible epoxy/MWCNT composites because of its fast cure kinetics after irradiation by a UV light source. The epoxy/MWCNT composites displayed low tensile properties because of the agglomeration of MWCNTs inside the epoxy matrix. In addition, the epoxy/MWCNT composites showed slightly lower thermal expansion with high electrical properties with a large amount of MWCNTs in the epoxy composites. • The synthesis and characterization of carbazole coating on TiO 2 nanoparticle as a new photosensitizer for fast curing epoxy composite with MWCNTs • The morphological, mechanical, thermal, and electrical properties of flexible epoxy composites after complete cure by UV technique.

Synthesis of Carbazoles by a Diverted Bischler–Napieralski Cascade Reaction

An unforeseen twist in a seemingly trivial Bischler–Napieralski reaction led to the selective formation of an unexpected carbazole product. The reaction proved to be general, providing access to a range of diversely substituted carbazoles from readily available substrates. Judicious variation of substituents revealed a complex cascade mechanism comprising no less than 10 elementary steps, that could be diverted in multiple ways toward various other carbazole derivatives.

Study on Palladium(II)-Catalyzed Mono-1-alkenylation of 9H-Carbazoles

AbstractA general and efficient method is reported for the direct mono-1-alkenylation of 9H-carbazole molecules with divalent palladium as a catalyst and an N-(2-pyridyl)sulfanyl directing group. This method also provides an efficient synthetic route for the synthesis of cross-dialkenylated carbazoles.

Tandem [2 + 2] Cycloaddition/Rearrangement toward Carbazoles by Visible-Light Photocatalysis

Reported herein is the first example of the synthesis of carbazoles via oxidative cyclization of 3-alkenylindoles with styrenes under visible light. The irradiation of a catalytic amount of [Ir(dtbbpy)(ppy)2][PF6] as the photocatalyst enables various 3-alkenylindoles and styrenes to undergo tandem [2 + 2] cycloaddition/rearrangement, thereby leading to carbazole derivatives in good to excellent yields under aerobic conditions. Mechanistic studies reveal that photoinduced energy transfer followed by electron transfer is responsible for the tandem reaction.

Efficient Copper-Catalysed Synthesis of Carbazoles by Double N-Arylation of Primary Amines with 2,2′-Dibromobiphenyl in the Presence of Air

AbstractAn efficient Cu-catalyzed synthesis of carbazole derivatives is reported, which proceeds by double C–N coupling reactions of 2,2′-dibromobiphenyl and amines in the presence of air. The reaction is robust, proceeds in high yields, and tolerates a series of amines including neutral, electron-rich, electron-deficient aromatic amines and aliphatic amines.