From Coal Tar to OLEDs: The Named Reactions That Build Carbazole

Carbazole does not look like a superstar. It is a modest tricyclic molecule, a five-membered nitrogen-containing pyrrole ring fused between two benzene rings, and for over a century chemists have pulled it out of coal tar by stripping away impurities such as anthracene. Yet this unassuming scaffold has become one of the most sought-after building blocks in modern chemistry, appearing everywhere from anti-cancer and anti-viral drug candidates to the glowing pixels of OLED displays. A new review published in Results in Chemistry by Talib Ansari and Rashid Ali of Jamia Millia Islamia now brings together, in a single alphabetical catalogue, every named reaction that chemists have deployed to build this remarkable molecule, along with the mechanistic reasoning that makes each one tick.

The appeal of carbazole begins with its electrons. Because the fused ring system is rigid, planar and richly π-conjugated, electron density can delocalize across all three rings, giving carbazole derivatives high fluorescence efficiency, efficient charge transport and excellent thermal stability. The nitrogen atom in the central ring further enhances charge-transfer behaviour, and derivatives that form charge-transfer complexes display red-shifted absorption and emission. These photophysical virtues explain why carbazole-containing polymers and small molecules have become staples of organic light-emitting diodes, organic field-effect transistors, photovoltaic cells and sensors. As hole-transport materials, they even suppress crystallization in small-molecule devices, extending operational lifetimes. More surprisingly, carbazole-based microporous polymers, built by exploiting the reactive hydrogen atoms at the 3- and 6-positions of the ring, can adsorb carbon dioxide at ambient temperature thanks to the electron-withdrawing nature of the nitrogen atom, opening an unexpected environmental application for this optical workhorse.

The medicinal story is equally compelling. The planar tricyclic framework facilitates π-π stacking and hydrogen bonding with DNA, enzymes and receptor proteins, allowing carbazole derivatives to interact with a striking range of biological targets. Compounds built on this scaffold have shown anti-cancer, anti-bacterial, anti-viral, anti-inflammatory and anti-oxidant activities, and strategic modification at various ring positions has tuned their pharmacokinetic and pharmacodynamic properties. It is this dual identity, drug lead and electronic material in one molecule, that makes the synthetic chemistry of carbazole worth cataloguing in exhaustive detail.

Ansari and Ali organize their review around named reactions, the eponymous transformations that serve as the shared vocabulary of synthetic organic chemistry. Just as doctors must know the names of organs, the authors argue, chemists must know their named reactions: the labels compress substrates, conditions and mechanisms into a single phrase that lets researchers think instantly about what a transformation can and cannot do. The review spans classical nineteenth-century chemistry, including the Bucherer, Graebe-Ullmann, Borsche-Drechsel and Fischer indole syntheses, alongside modern metal-catalyzed and photocatalytic methods such as the Ackermann reaction, Cadogan cyclization, Knölker synthesis and ring-closing metathesis.

The classical routes remain surprisingly relevant. The Borsche-Drechsel cyclization, first reported by Edmund Drechsel in 1888 and elaborated by Walther Borsche in 1908, condenses arylhydrazines with cyclohexanones to form hydrazones that undergo protonation, ene-amine tautomerization and a [3,3]-sigmatropic rearrangement, ultimately delivering tetrahydrocarbazoles that can be aromatized to the parent scaffold. This venerable sequence has carried chemists to an impressive roster of natural products, including murrayanine from the stem bark of Murraya koenigii, murrayacine, clausenol and the antifungal algal alkaloids Tjipanazole D and I. In a green-chemistry twist, Kotha’s team recently performed the Borsche-Drechsel cyclization in a deep eutectic solvent, a low-melting mixture of N,N’-dimethyl urea and L-(+)-tartaric acid, replacing harsh classical media with a sustainable alternative.

The Fischer indole synthesis, discovered by Emil Fischer in 1883, follows a closely related mechanistic logic: phenylhydrazines condense with aldehydes or ketones to form hydrazones, which tautomerize, rearrange sigmatropically and cyclize with loss of ammonia to deliver indole frameworks, including fused carbazoles. It was this strategy that Bonjouklian and co-workers used to reach Tjipanazole E and B, chlorinated carbazole alkaloids bearing N-glycosidic substituents that were first isolated from the blue-green alga Tolypothrix tjipanasensis. Meanwhile, the Bucherer carbazole synthesis, reported by Hans Theodor Bucherer in 1908, couples naphthols with arylhydrazines under acidic bisulfite conditions without any transition metal, proceeding through hydrogen sulfite addition, a [3,3]-sigmatropic rearrangement and final ammonia elimination to yield benzo-fused carbazoles.

On the modern side, palladium catalysis dominates. The Buchwald-Hartwig coupling, independently discovered by Stephen Buchwald and John Hartwig in 1994, forms carbon-nitrogen bonds between amines and aryl halides through the canonical catalytic cycle of oxidative addition, amine binding, deprotonation and reductive elimination. Zhou and Verkade showed that a double N-arylation of primary amines with 2,2′-dihalobiphenyls, mediated by a proazaphosphatrane ligand, delivers N-substituted carbazoles in a single operation. The method’s excellent functional-group tolerance made it the key step in the 2008 total synthesis of murrayazoline, an antiplatelet carbazole alkaloid from the genus Murraya. The related Ackermann reaction chains a Buchwald-Hartwig coupling with a direct arylation to build carbazoles from simple anilines and 1,2-dihaloarenes, a domino strategy that was used to synthesize murrayafoline A, a growth-inhibitory and fungicidal alkaloid isolated from Rutaceae plants.

Other modern methods trade metal catalysis for other tricks. The Cadogan cyclization, reported by John Cadogan in 1974, reductively cyclizes o-nitrobiphenyls with triethyl phosphite or triphenylphosphine, proceeding through nitroso intermediates and either a nitrene or a direct cyclization pathway; it underpinned the synthesis of siamenol, an anti-HIV carbazole alkaloid from Murraya siamensis. Microwave irradiation now compresses Cadogan reaction times from hours to minutes, and a visible-light variant using the organic photocatalyst 4CzIPN under blue LEDs delivers carbazoles in 40 to 87 percent yields. The Knölker synthesis, introduced by Hans-Joachim Knölker in 1999, takes a different approach entirely: a tricarbonyliron fragment protects a reactive cyclohexadiene, enforces anti-selective stereochemistry and enables hydride abstraction with triphenylmethyl tetrafluoroborate, a sequence that made possible the first total synthesis of the complete antiostatin A and B families. Ring-closing metathesis, the Nobel-recognized chemistry of Grubbs, Schrock and Chauvin, closes carbazole rings from pre-installed dienes under mild conditions and delivered murrayaquinone A, while the Wulff-Dötz benzannulation, in which a Fischer chromium carbene complex reacts with an alkyne through carbon monoxide insertion and 6π-electrocyclization, constructed the carbazole core of the Aspidospermidine alkaloids.

What emerges from the survey is not merely a catalogue but a decision framework. Each reaction carries trade-offs: the Graebe-Ullmann synthesis is reliable but demands temperatures above 200 degrees Celsius; the Cadogan cyclization is metal-free but generates stoichiometric phosphine oxide waste; the Buchwald-Hartwig coupling is modular but requires costly palladium and pre-halogenated substrates; the Knölker synthesis offers stereocontrol but demands specialized iron chemistry. The diverted Bischler-Napieralski cascade reported by Faltracco in 2021 illustrates how even well-worn reactions can surprise, delivering an unexpected carbazole instead of the anticipated dihydro-β-carboline through a spirointermediate pathway. By assembling these options side by side, with their mechanisms, substrate requirements and validated natural product targets, the review gives synthetic chemists a practical map for choosing the right tool, and gives students a masterclass in how the vocabulary of named reactions organizes more than a century of heterocyclic chemistry.

Subject of Research: Named reactions for the synthesis of carbazole and their mechanistic and applied significance

Article Title: Named reactions in Carbazole synthesis: Mechanistic insights and potential applications

Article References: Ansari, T., & Ali, R. (2026). Named reactions in Carbazole synthesis: Mechanistic insights and potential applications. Results in Chemistry, 31, Article 103913. https://doi.org/10.1016/j.rechem.2026.103913

Image Credits: AI Generated

DOI: 10.1016/j.rechem.2026.103913

Keywords: carbazole, named reactions, organic synthesis, heterocyclic chemistry, Buchwald-Hartwig coupling, Fischer indole synthesis, Knölker synthesis, ring-closing metathesis, natural products, OLEDs, medicinal chemistry, palladium catalysis