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Azulene

Azulene is a non-benzenoid aromatic with the molecular formula C₁₀H₈, featuring a fused and ring system that forms a bicyclic [5.3.0] structure with 10 π electrons delocalized across the rings. This is notable for its vivid blue color, arising from intramolecular charge transfer that results in a significant of approximately 1.08 D, contrasting sharply with its colorless naphthalene, which has zero . Azulene was first isolated in 1863 by British chemist Septimus Piesse from the azure-blue distillates of essential oils derived from plants such as yarrow () and wormwood (), though its structure was not elucidated until later. The correct bicyclic structure was established in 1926 by Lavoslav Ružička through analysis of guaiazulene, a naturally occurring derivative from guaiac wood oil, and confirmed via and degradation studies. The first of azulene was achieved in 1937 by A. S. Pfau and Placidus Plattner, involving a multi-step process based on ring expansion of a hydroazulenone intermediate, followed by and dehydrogenation. Key properties of azulene include its unusual , where the five-membered ring behaves as a and the seven-membered ring as a in the resonance hybrid, contributing to its stability and polar nature. It exhibits a of 99–100 °C and boils at 170 °C under reduced pressure, with low in but good in solvents. Azulene occurs naturally as a component of essential oils from plants such as German chamomile (Matricaria recutita), primarily in the form of derivatives like , which provide effects. In applications, azulene and its derivatives are used in for their soothing and properties, particularly in treating irritations, and have been explored in for potential antineoplastic and nonlinear optical materials due to their electronic properties.

Introduction

Overview

Azulene is a bicyclic aromatic with the molecular formula C₁₀H₈, serving as a of but distinguished by its fused five- and seven-membered rings forming a 10 π-electron system. Unlike the colorless , azulene exhibits a distinctive color arising from an intramolecular charge-transfer transition associated with its polarized structure, which shifts absorption into the . Compounds featuring the azulene skeleton occur naturally as pigments in various biological sources, including certain mushrooms, guaiac wood oil derived from the tree , and essential oils such as those from and yarrow. These natural azulene derivatives, like guaiazulene, contribute to the blue hues observed in these materials and have been utilized in traditional applications for centuries. The name "azulene" derives from the Spanish word "azul," meaning blue, and was coined in 1863 by the British chemist Septimus Piesse upon isolating the compound from distillates of essential oils.

History

Azulene was first isolated in 1863 by British chemist and perfumer Septimus Piesse from the azure-blue distillate obtained during steam distillation of essential oils from plants such as chamomile, yarrow, and wormwood. Piesse named the compound "azulene," derived from the Spanish word "azul" meaning blue, to reflect its distinctive vivid color, which arises from its presence as a chromophore in various plant essential oils including those from chamomile, yarrow, and wormwood. The structural elucidation of azulene progressed in the and amid efforts to characterize natural blue oils. In 1926, Lavoslav Ružička proposed an initial structure for guaiazulene, a common natural derivative, but it was Placidus A. Plattner and Alexander Pfau at the who definitively established the fused cyclopenta-fused cycloheptene skeleton in 1936 through degradative studies and comparative analyses of natural isolates. Their work clarified the non-benzenoid bicyclic framework, resolving earlier uncertainties about the arrangement of its 10 carbon atoms and distinguishing it from isomers. Building on this foundation, Plattner and Pfau achieved the first of azulene in 1936 via a multi-step ring expansion route starting from cyclopentenocycloheptanone, an intermediate derived from 1,6-cyclodecadiene, followed by dehydrogenation to yield the in low but confirmatory yields. This milestone enabled further exploration of azulene's properties beyond natural extracts. In the 1950s, with the advent of more accessible synthetic routes like the Hafner method involving and acetylene derivatives, researchers began detailed investigations into azulene's electronic structure. Early studies highlighted its nonalternant , satisfying Hückel's 4n+2 π-electron rule across the fused rings despite unequal bond lengths, and measured its unexpectedly large of approximately 1.0 D—attributed to charge separation between the five- and seven-membered rings—contrasting sharply with the nonpolar . These findings, including theoretical calculations and spectroscopic analyses, underscored azulene's unique reactivity and optical properties.

Properties

Physical Properties

Azulene has the molecular formula \ce{C10H8} and a of 128.17 g/. It appears as dark blue crystalline solid with a of 98–100 °C and a of 242 °C at standard pressure. The density of the liquid is 0.987 g/cm³ at 25 °C. Its relatively high boiling point can be briefly attributed to contributions from aromatic stability. Azulene shows low solubility in water, with a value of 0.015 g/L at 25 °C, rendering it effectively insoluble for most practical purposes. In contrast, it is readily soluble in common organic solvents such as , , and , facilitating its handling in non-aqueous media. The characteristic blue color of azulene arises from absorption in the , primarily due to the weak \ce{S0 -> S1} transition with a maximum around 580 nm (\epsilon \approx 200 M^{-1} cm^{-1}), while a stronger \ce{S0 -> S2} appears at approximately 340 nm (\epsilon \approx 5000 M^{-1} cm^{-1}). These spectroscopic features are key for identification and arise from the molecule's non-alternant . The standard of of azulene is −5290.7 / for the at 298 . This value underscores its thermodynamic relative to products like CO_2 and H_2O.

Chemical Properties

Azulene demonstrates notable , a consequence of its aromatic stabilization energy, which arises from the delocalized 10 π-electron system across its fused five- and seven-membered rings. This is evidenced by its high of formation in the gas phase, Δ_f H°_m(g) = 309.2 ± 4.9 / at 298.15 , derived from measurements. The standard molar of for azulene is Δ_c H°_m = −(5285.5 ± 4.9) /, indicating a robust energetic barrier to under standard conditions. In terms of reactivity, azulene shows a distinct in , with the 1- and 3-positions in the five-membered ring being most reactive due to elevated at these sites. This preference is observed across various electrophiles, including nitrating and halogenating agents, where substitution at the 1-position predominates, while the 2-position in the five-membered ring and positions in the seven-membered ring exhibit lower reactivity. Such behavior underscores azulene's resistance to substitution at less activated sites, preserving its core structure under mild electrophilic conditions. The molecule's uneven charge distribution, stemming from resonance structures that polarize the π-system, imparts a permanent of 1.08 D along the long axis. This polarity, unusual for a neutral like its naphthalene (which has zero ), contributes to azulene's characteristic blue color through intramolecular charge transfer. Basic thermodynamic properties further characterize its behavior; for instance, the constant-pressure of gaseous azulene at 298.15 is 128.41 J/mol·K. Azulene also exhibits anomalous photophysical behavior by violating , emitting from the second excited (S₂) rather than the lowest (S₁). This arises because the S₁ state is antiaromatic, promoting rapid nonradiative decay to the via a , whereas the S₂ state maintains aromatic character with minimal geometric relaxation and a large S₂–S₁ energy gap (~14,000 cm⁻¹) that hinders .

Structure and Bonding

Molecular Geometry

Azulene possesses a bicyclic composed of a fused five-membered ring and a seven-membered ring, sharing two adjacent carbon atoms to form a 10-carbon perimeter. This fused ring system results in a compact, non-alternant framework with the C₁₀H₈. The molecule adopts a fully planar conformation, as confirmed by , , and studies, with no significant out-of-plane deviations in the gas or solid phases. This planarity facilitates efficient π-orbital overlap across the ring system. Bond lengths exhibit minimal alternation, reflecting uniform electron distribution; experimental data indicate peripheral C-C bonds averaging 1.403 , while the central transannular bond (between positions 9 and 10) measures 1.501 . Representative values include the C1-C2 bond at 1.37 in the five-membered ring and the C3-C4 bond at 1.40 in the seven-membered ring, consistent with both and high-level computational geometries. In the solid state, azulene crystallizes in the monoclinic P2₁/c, but its is complicated by dynamic , leading to high correlations in atomic positional parameters and challenges in refinement. Invariom modeling has been employed to accurately describe the , revealing a planar molecular core with intermolecular distances influenced by van der Waals interactions and the inherent . Lattice energy minimizations indicate close-packed layers with minimal deviations from the ideal geometry, though results in averaged occupancies for certain atoms in the packing.

Aromaticity and Electronic Properties

Azulene possesses a 10 π-electron system delocalized over its fused five- and seven-membered rings, satisfying for with n=2 in the 4n+2 formulation. This configuration confers overall aromatic stability, despite the non-alternant structure that distinguishes it from or . The molecule's planarity and cyclic conjugation further support this aromatic character, enabling efficient π-overlap across the bicyclic framework. The electronic structure of azulene exhibits unequal π-electron distribution, arising from resonance forms that depict the five-membered ring as a (6 π electrons) and the seven-membered ring as a (6 π electrons), with charge separation leading to higher in the five-membered ring and relative deficiency in the seven-membered ring. This polarization results in a permanent of approximately 1.0 D, with the negative end at the five-membered ring. The non-uniform distribution underlies azulene's reactivity preferences and photophysical anomalies. Frontier molecular orbitals in azulene display reduced symmetry due to its non-alternant nature, with the highest occupied (HOMO) localized more on the five-membered ring and the lowest unoccupied (LUMO) on the seven-membered ring, leading to minimal overlap and a relatively narrow HOMO-LUMO gap compared to alternant hydrocarbons like . This gap, typically around 2.1 eV from optical transitions, facilitates accessible excited states and contributes to the molecule's color. A hallmark of azulene's photophysics is its anti-Kasha emission, where fluorescence predominantly occurs from the second excited (S₂) to the (S₀) rather than from the lowest excited (S₁), violating . This behavior stems from the forbidden nature of the S₁ → S₀ transition, attributed to symmetry selection rules and a large energy gap (∼14,000 cm⁻¹) between S₁ and S₂, which minimizes from S₂ to S₁. Recent studies through 2025 have elucidated the excited-state dynamics of azulene, emphasizing the roles of energy gaps and vibronic coupling in modulating . Ultrafast spectroscopy reveals rapid S₂ relaxation pathways influenced by interactions and effects, with vibronic couplings driving efficient nonradiative decay from higher states while preserving S₂ quantum yields up to 0.3 in . These investigations highlight how perturbations in the S₁-S₂ gap can enable dual or suppress anti-Kasha behavior in derivatives, informing design of novel fluorophores.

Synthesis

Early Syntheses

The first of azulene was achieved in 1937 by Placidus A. Plattner and Alexander S. Pfau through a ring expansion strategy starting from . The key step involved the addition of diazoacetic ester to indane, which inserted a carbon unit into the five-membered ring, forming a derivative after . Subsequent and dehydrogenation yielded azulene, though the overall process was multi-step and suffered from low efficiency. This pioneering route established the bicyclic [5.3.0] framework but was limited by modest yields due to side reactions during the carbene insertion and incomplete requiring harsh conditions like oxidation. Purification posed significant challenges in these early efforts, as the vivid blue color of azulene facilitated visual detection but complicated isolation from colorless byproducts and polymeric impurities formed during dehydrogenation. The product often required repeated or under reduced pressure to achieve purity, highlighting the technical hurdles in handling such a reactive, colored . Despite these issues, the Plattner-Pfau synthesis provided the first unambiguous confirmation of azulene's structure, aligning with spectroscopic and degradative studies from natural sources. In the , alternative routes emerged, including the Ziegler-Hafner method, which utilized fulvene intermediates in a cyclization approach. This involved generating 6-dimethylaminofulvene from and a pyridinium salt, followed by reaction with under basic conditions to form a seven-membered ring precursor, and final aromatization via dehydrogenation. Yields for this sequence reached 50-60% in optimized variants, a marked improvement over prior methods, though it still demanded careful control to avoid fulvene . The exemplified the growing use of Diels-Alder-inspired cycloadditions with fulvenes as dienes, enabling substitution patterns on the five-membered ring. These early syntheses underscored the synthetic challenges of constructing azulene's non-alternant aromatic system, with common limitations including poor in ring expansions and the need for vigorous dehydrogenation steps that reduced overall efficiency to below 20% in most cases. For instance, the diazoacetic addition in the Plattner-Pfau route could be represented conceptually as undergoing carbene insertion to yield a tropylium-like intermediate, followed by CO₂ loss and H₂ abstraction, though practical execution often introduced skeletal rearrangements. Such approaches paved the way for later refinements but remained labor-intensive for preparative scales.

Modern Methods

Since the mid-20th century, synthetic approaches to azulene have evolved toward more efficient, scalable methods that leverage and mild conditions to overcome the limitations of classical multi-step routes. These modern techniques, developed from the onward, emphasize one-pot processes, transition-metal , and assisted cycloadditions to enable the construction of the azulene core and its fused variants with improved yields and selectivity. One notable advancement is the one-pot via pyridine-mediated cycloadditions, which utilizes Zincke aldehyde derivatives from salts reacting with cyclopentadienyl anions. This process involves ring opening of the salt to form a Zincke intermediate, followed by condensation with under basic conditions (e.g., ), and subsequent 10π electrocyclic cyclization with elimination to afford the azulene framework. Recent implementations, including microwave-assisted variants, have achieved yields up to 64% for substituted azulenes like 6-methylazulene, highlighting the method's convenience for accessing functionalized derivatives. Transition-metal-catalyzed routes have significantly expanded azulene synthesis, particularly through palladium-mediated couplings that facilitate ring fusion. For instance, Pd-catalyzed cross-coupling reactions, such as and , enable the attachment of aryl or heteroaryl groups to azulene's five- or seven-membered rings, followed by intramolecular cyclization to form fused systems. These methods, reviewed in 2021, typically employ PdCl₂(dppf) or similar catalysts with bases like K₃PO₄, yielding aryl-substituted azulenes in 70-95% efficiency and allowing precise control over substitution patterns for extended polycyclic architectures. Recent bottom-up syntheses (2022-2025) for azulene-embedded nanographenes have integrated Suzuki-Miyaura coupling with acid-mediated cyclization to construct complex fused structures. In a 2025 approach, 2-chloroazulenes bearing 1,3-ester groups undergo Pd-catalyzed Suzuki-Miyaura coupling with arylboronic acids (e.g., 1-naphthalenboronic acid) using PdCl₂(dppf) and K₃PO₄, affording biaryl intermediates in 71-97% yields. Subsequent Brønsted acid-mediated intramolecular cyclization with (MeSO₃H) at 100°C promotes ring closure, yielding azuleno[2,1-a]phenalenones in 71-99% yields, which exhibit unique optical and electrochemical properties suitable for materials applications. High-yield variants of Diels-Alder-type s, enhanced by assistance, provide rapid access to azulene scaffolds. A key example is the -promoted [6+4]- of 6-aminofulvene with α-pyrones, which proceeds under solvent-free or low-solvent conditions to form azulene-indole adducts, followed by CO₂ extrusion and . Developed in but representative of ongoing optimizations, this method accelerates reaction times to minutes while delivering yields exceeding 80% for antineoplastic azulene-indoles, demonstrating scalability for pharmaceutical precursors. Brønsted acid cyclizations have emerged as versatile tools for assembling fused azulene systems from prefunctionalized precursors. In 2022, [8+2] cycloaddition of 2H-cycloheptafuran-2-ones with enamines yielded benzazulene derivatives, which were then subjected to Brønsted acid-mediated (e.g., 100% H₃PO₄) intramolecular cyclization via with , followed by dehydration and deprotection, affording unsubstituted benzazulenes in high yields as the most efficient route reported. Similarly, a 2023 method employs polyphosphoric acid (PPA) at 140°C to cyclize 1,3-diethoxycarbonyl-2-arylaminoazulenes through and Friedel-Crafts acylation with decarboxylation, producing azuleno[2,1-b]quinolones in 85-100% yields. These acid-promoted strategies underscore the role of strong Brønsted acids in driving regioselective ring fusions under mild thermal conditions.

Derivatives

Natural Derivatives

Azulene derivatives occur naturally in various biological sources, predominantly as sesquiterpenoids with alkyl substitutions that modify their blue pigmentation and volatility. These compounds contribute to the coloration and aromatic profiles of essential oils extracted from plants and fungi. Guaiazulene, a sesquiterpene featuring methyl and isopropyl groups on the azulene core, is primarily isolated from the essential oil of guaiac wood derived from Guaiacum officinale trees. Chamazulene, a related sesquiterpene with ethyl substitution, is obtained from German chamomile (Matricaria recutita L.) via steam distillation, during which the precursor matricin converts to chamazulene, imparting anti-inflammatory properties. These oils are obtained via steam distillation, a process that efficiently captures volatile components while converting precursors in chamomile to related azulenes. Guaiazulene imparts a deep blue hue and woody, rose-like aroma, making it valuable in perfumery to enhance fragrance depth and stability. In fungal sources, azulene derivatives are present in certain mushrooms, including species within the order such as Omphalotus, where they arise from the oxidation of sesquiterpenes like lactarofulvenol and contribute to the vivid blue-green latex exuded by injured fruiting bodies. These compounds can be isolated through solvent extraction followed by chromatographic separation from the fungal biomass. Marine also harbor azulene-based metabolites, notably hydroazulene diterpenes isolated from of the , such as Dictyota volubilis, using solvent partitioning and purification techniques to yield structurally diverse variants with oxygenated functionalities. Among structural variations, alkylated azulenes like vetivazulene—a dimethyl-isopropyl derivative—are extracted from vetiver root oil () via , yielding a component that adds earthy notes to the oil's complex profile.

Synthetic Derivatives

Hydroxyazulenes represent key synthetic derivatives of azulene, prepared through targeted modifications to introduce hydroxyl groups at specific ring positions, altering their electronic and acidic properties. 1-Hydroxyazulene, synthesized by the reduction of 1-acetoxyazulene with lithium aluminum hydride, exists as an unstable green oil that resists keto-enol tautomerism due to the high energy barrier for rearrangement. Its relatively low acidity reflects behavior comparable to non-aromatic alcohols rather than typical phenols. In contrast, 2-hydroxyazulene, obtained via hydrolysis of 2-methoxyazulene with hydrobromic acid, is stable and undergoes keto-enol tautomerism, with the enol form predominating. This isomer exhibits unusual acidity due to enhanced stabilization of the conjugate base by the azulene π-system. Ring-fused azulenes have seen significant advances in between 2022 and 2025, yielding linear polycyclic hydrocarbons with embedded azulene motifs that exhibit small HOMO-LUMO bandgaps, often below 2 , enabling applications in . For instance, azuacenes—fused systems combining azulene with linear acenes in a 6-7-5 ring —have been prepared through stepwise cyclization and reactions, demonstrating bandgaps as low as 1.75 alongside improved ambient compared to alternant polycyclic aromatic hydrocarbons. Similarly, a nonalternant pentacene incorporating two azulene units achieves an optical bandgap of 2.046 and extended under air exposure, attributed to the nonalternant disrupting reactive edge sites. Azulene-fused linear polycyclic aromatic hydrocarbons, synthesized in four steps from commercial azulene, further highlight small bandgaps (around 1.8 ), high up to 300°C, and reversible color changes under acid/base stimuli. Azulene-based conjugated polymers, accessed through 2,6-functionalization, have emerged as a innovation, leveraging the less reactive positions in the five-membered ring for polymer backbone construction. These polymers, synthesized via direct arylation polycondensation of 2,6-dihaloazulene monomers with comonomers like or , display extended conjugation with bandgaps of 1.9–2.2 eV and proton-responsive quenching, arising from azulenium ion formation. A C-H strategy enables tuning of dipole orientation in 2,6-azulene copolymers, yielding unipolar n-type with electron mobilities up to 0.5 cm² V⁻¹ s⁻¹ and balanced HOMO/LUMO levels for applications. Functional groups at positions 1 and 3 of azulene serve as critical handles for tuning reactivity in synthetic derivatives, exploiting the high electron density at these nucleophilic sites in the seven-membered ring. readily introduces substituents like or alkyl groups at 1,3-positions, modulating the and ; for example, 1,3-dichloroazulene derivatives exhibit shifted absorption maxima by 50 nm compared to unsubstituted azulene. Palladium-catalyzed cross-coupling reactions, such as Suzuki-Miyaura or Sonogashira, further enable precise installation of aryl or alkynyl groups at these positions under mild conditions, enhancing and conjugation length while preserving . This regioselective functionalization has facilitated derivatives with tailored electrophilicity, as seen in 1,3-bis(ethynyl)azulenes used as building blocks for extended π-systems.

Coordination and Organometallic Chemistry

Azulene as a Ligand

Azulene serves as a versatile in coordination chemistry owing to its nonalternant aromatic structure, which enables diverse binding modes to transition metals. Its fused five- and seven-membered s allow for ambidentate coordination, where the can interact with metal centers through either system, often exhibiting hapticities ranging from η² to η⁶ depending on the metal fragment and conditions. This flexibility arises from azulene's zwitterionic , with the five-membered ring acting as an electron-rich donor and the seven-membered ring as an electron-deficient acceptor, facilitating adaptation to the electronic demands of the metal. A prominent binding mode is η⁶-coordination through the seven-membered ring, which mimics the π-system of and donates six electrons to the metal, as seen in complexes with early transition metals and group 6 elements. In such interactions, the seven-membered ring's conjugated π-electrons engage the metal center, leading to stable sandwich-like or half-sandwich structures, while the five-membered ring remains uncoordinated or participates minimally. This mode is particularly favored in mononuclear complexes where the metal requires a , aromatic η⁶-ligand, enhancing the through back-donation from the metal to the ligand's π*-orbitals. The ambidentate behavior of azulene allows it to bind selectively through the five-membered ring in η⁵-fashion, resembling , or through the seven-membered ring in η⁴- or η⁶-modes, enabling haptotropic shifts between rings in response to steric or electronic perturbations. For instance, in dinuclear complexes, one metal may coordinate to the five-membered ring while another binds the seven-membered ring, promoting bridging architectures and isomerism. This dual-site coordination is influenced by spectator ligands on the metal, which can trigger rearrangements to optimize metal-ligand overlap. Azulene's inherent of approximately 1.0 D, with partial negative charge on the five-membered ring and positive on the seven-membered ring, significantly modulates metal-ligand interactions by directing charge transfer and stabilizing polar bonds. This enhances the ligand's ability to stabilize low-valent metals through donation from the electron-rich five-membered ring or acceptance into the electron-poor seven-membered ring, influencing reactivity in catalytic processes. The also contributes to selective in asymmetric environments, where the ligand's aligns with the metal's electrostatic . Recent advances have leveraged azulene's coordination properties in , notably in 2025 reports of metallacycles formed from azulene-derived dipyridyl ligands and Cp*Rh building blocks. These structures assemble via η²-coordination of the pyridyl arms to the centers, with the azulene providing rigidity and π-stacking for dimerization, yielding photocatalytically active cages for oxidation. Such assemblies highlight azulene's role in constructing functional supramolecular architectures with tunable electronic properties.

Notable Complexes

One notable organometallic complex involving azulene is (azulene)Fe₂(CO)₅, a dinuclear iron compound where azulene bridges two iron centers with an overall formula of C₁₀H₈Fe₂(CO)₅. The structure features five carbonyl ligands distributed across the two iron atoms, with azulene coordinating in a bidentate fashion through its five- and seven-membered rings, exhibiting variable (typically η⁵:η³) that allows for bridging. This complex is synthesized via reactions of azulene with iron carbonyl precursors like Fe₂(CO)₉, leading to stable dinuclear species, though detailed synthetic conditions are often explored computationally for optimization. Another prominent example is (azulene)Mo₂(CO)₆, a well-established dinuclear complex with the (η⁵,η⁵-C₁₀H₈)Mo₂(CO)₆. In this structure, azulene serves as a between the two molybdenum atoms, each bearing three terminal CO ligands, resulting in a symmetric coordination where the metal-metal bond is supported by the asymmetric nature of azulene's rings. The complex is prepared by refluxing azulene with Mo(CO)₆ or related precursors in nonpolar solvents, yielding a stable product characterized by its hapticity-driven bonding. Recent advancements include azulene-based metallacycles developed for sensing applications. These triangular metallacycles (e.g., [CpRh]₃(azulene-derived )₃) are self-assembled at from a CpRh building block and dipyridyl azulene ligands in /dimethylaniline mixtures, confirmed by NMR, , and showing π-π stacked dimers with interplanar distances of 3.6–3.9 . The complexes exhibit UV-vis absorption at 330 nm and 410 nm due to π–π* transitions and demonstrate high photostability, enabling efficient visible-light-driven photooxidation of sulfides to sulfoxides with yields up to 97% in 4 hours, recyclable over three cycles. Regarding stability and reactivity, these azulene complexes generally display robust due to the bridging ligand's to accommodate different metal oxidation states, but they exhibit fluxional behavior in solution involving haptotropic shifts between ring coordination modes. substitution patterns are common, with labile terminal ligands allowing replacement by phosphines or isonitriles under mild heating, as seen in analogous systems where leads to new dinuclear variants without disrupting the core structure.

Applications

Materials and Optoelectronics

Azulene-fused polycyclic aromatic hydrocarbons (PAHs) have emerged as promising materials for small-bandgap semiconductors due to their extended π-conjugation and tunable electronic properties. In 2025, efficient syntheses of such azulene-fused systems, including azuleno[2,1-a]phenalenones, were reported using Suzuki–Miyaura coupling followed by Brønsted acid-mediated cyclization, yielding compounds with distinctive optical absorption in the near-infrared region and electrochemical stability suitable for semiconductor applications. Earlier work demonstrated that linear azulene-fused PAHs exhibit optical bandgaps as low as 1.0 eV, enabling their use in organic field-effect transistors and photovoltaic devices with high charge carrier mobilities. Additionally, 2025 advancements in Scholl-type oxidation of 1,2,3-triarylazulenes produced embedded azulene PAHs with enhanced planarity and reduced bandgaps, further optimizing them for low-energy optoelectronic functions. Conjugated polymers incorporating azulene units offer exceptional stability and reversible responses to external stimuli, making them ideal for such as sensors and devices. These polymers leverage the seven-membered of azulene to achieve unique connectivity that promotes stimuli-responsiveness, including pH- or redox-triggered color changes and conductivity modulation without degradation. For instance, azulene-based polythiophenes demonstrate high thermal stability up to 400°C and reversible switching in field-effect transistors upon , attributed to the formation of aromatic azulenium cations that alter the bandgap reversibly. This responsiveness stems from azulene's inherent and non-alternant structure, enabling applications in where durability under operational stresses is critical. The optoelectronic properties of azaazulenes, nitrogen-substituted analogs of azulene, feature narrow bandgaps and tunable . These compounds exhibit potential for deep-red to near-infrared absorption suitable for organic light-emitting diodes and bioimaging probes due to their non-alternant electronic structure.

Biological and Medicinal Uses

Guaiazulene, a derivative of azulene found in essential oils from plants such as , exhibits significant properties by inhibiting release and reducing in animal models. In clinical applications, topical formulations containing 0.02% guaiazulene alleviate itching in patients, while 0.05% ointments promote healing of in newborns within three days and prevent nipple fissures during . Sodium guaiazulene , a water-soluble derivative, is employed for its wound-healing effects in treating and oral canker sores due to its ability to soothe mucosal . In , guaiazulene serves as an FDA-approved colorant and in skincare products, leveraging its and activities to reduce skin irritation. Photodynamic therapy (PDT) incorporating azulene derivatives shows promise in as photosensitizers. When activated by red laser light (625–638 nm), azulene generates , leading to (ROS) production that decreases viability of peripheral blood mononuclear cells (PBMCs) at concentrations of 15 μM and energy densities of 4.2–200 J/cm², with an inverse correlation between yield and cell survival (Spearman's r = -0.610). Similarly, guaiazulene at 2–5 μM under 4–8 J/cm² irradiation suppresses inflammatory markers like RANTES and PGE₂ in TNF-α-stimulated PBMCs without compromising cell viability, suggesting targeted against tumor cells via ROS-mediated . Pulsed laser modes with intermittency factors of 5–9 enhance formation up to threefold at low azulene doses (1–10 μM), improving immunosuppressive effects potentially applicable to photodynamic cancer treatments. Azulene derivatives occur naturally in fungi, such as mushrooms and theaecolum, where they contribute to blue pigmentation by absorbing light in the 500–700 nm range. In these organisms, azulenes function in defense mechanisms, exhibiting and activities that inhibit pathogens like , thereby protecting against microbial invasions and environmental stressors. This pigmentation and bioactivity likely aid in ecological roles, including UV protection and deterrence of herbivores or competitors in fungal habitats. Studies on hydroxyazulene (azulenol) tautomerism reveal varying acidity among isomers, with 6-hydroxyazulene displaying the strongest acidity in vacuo—greater than phenol or naphthols—while 1-hydroxyazulene is the weakest; keto tautomers influence and acid-base behavior, which could inform proton-transfer mechanisms in . Azulene and its derivatives generally exhibit low profiles. Oral LD50 values for azulene are 3 g/kg in mice and 4 g/kg in rats, while guaiazulene has an LD50 of 1.55 g/kg in rats, indicating minimal acute risk at therapeutic doses with no systemic side effects from topical use, though rare allergic reactions like may occur.