Syntheses of Azulene Embedded Polycyclic Compounds

Abstract

This review focuses on obtaining embedded azulene polycyclic molecules treated according to their particular structure. The division of material into the azulene unit grafted only on one or two bonds and poly-fused azulene compounds was suggested with the intention of facilitating the presentation and assimilation of information. The similarity of some structural features in the compounds included in different analyzed classes results in the presence of the same synthesis protocol in several places. Obtaining benz[a]azulenes, azulene-fused acenes, and helicenes or azulene-embedded nanographene, along with other compounds, is presented.

1. Introduction

The syntheses and properties of compounds with azulene as a building key block have constantly attracted the attention of researchers. The difference in behavior between this aromatic non-alternating system and that of benzenoid aromatic systems in which the double bonds alternate endows azulene and its compounds with very special features. Supplementary, the fact that the azulene core has only one axis symmetry compared with its alternant isomer, naphthalene, with symmetry to both axes, also contributes to the differences between these systems.

The properties and a series of optical, electronic, and biological applications [1,2,3] of the extra-grafted azulenes have boosted research in the synthesis of such interesting compounds. Therefore, several reviews, especially those addressed to the skilled in the field, deal with the building of polycondensed aromatic compounds (PAHs) containing azulene. Some of them reported general syntheses of these compounds [4,5], while others referred to a specific synthesis route [6,7,8] or to obtaining some compounds with a particular structure [9]. The present review is focused on obtaining embedded azulene polycyclic molecules, which are briefly treated according to their structure. In this way, the reader can see the diversity of syntheses that lead to similar structures. The division of the material into the azulene unit grafted on only one or two bonds and poly-fused compounds is arbitrary and was suggested with the intention of facilitating the presentation. For systematic information and to achieve progress related to the proposed subject over time, it was also considered useful to present some compounds that have been reported from the early studies along with the most recent results. The azulene bond(s) in which the condensation takes place is decisive both in the synthesis of the compounds and in their properties. Aromatic or heteroaromatic ring(s), as well as other moieties, can be grafted to one or more condensed azulenes. A chapter is dedicated to graphenes that contain azulene system(s) as defects in their structure. The reviewed syntheses can start from compounds containing the azulene system or have azulene precursors that are converted to this skeleton. For the presentation, instead of a long discussion, it was preferred to introduce synthesis schemes that include the reaction conditions and the yields of the obtained products. Because of the moderate number of examples and the reduced space given to each example due to the limits accepted for a review, this paper is addressed less to those skilled in azulene chemistry but to the researchers who want a brief overview of this subject.

2. Compounds with Azulene Unit Grafted Only on One or Two Bonds

This chapter presents the building of some molecules in which an azulene unit is grafted on only one or two bonds with a wide variety of aromatic or nonaromatic, carbo or heterocyclic systems which can be considered azulene-embedded “oligocyclic” structures.

2.1. Benz[a]azulenes

The history of benz[a]azulene, a structural isomer of anthracene, with benzene attached to the five-membered ring of azulene, began in 1948 when Plattner et al. [10] and Treibs [11] obtained it in the reaction of fluorene with ethyl diazoacetate. Since then, several research groups have been interested in terms of its structural and optical properties as well as for structurally related molecules. As a result, over time, an important number of synthesis procedures for these products were developed, of which only a few, based on the diversity of their obtaining routs, will be exemplified.

Thermal decomposition of the sodium salts of benzocyclobutenone tosylhydrazones 1.1 in benzene afforded 9a,10-dihydrobenz[a]azulenes 1.2 [12]. The dehydrogenation by hydride abstraction with the trityl cation followed by deprotonation afforded benz[a]azulene 3. The research of Wege et al. led to the proposal of the mechanism described in Scheme 1 (Steps 2 to 4). The addition of carbene (I) to the benzene gives the norcaradiene derivative (II), which isomerizes to the cycloheptatriene (III). After the conrotatory electrocyclic ring opening of the benzocyclobutene moiety in (III), the resulting extended intermediate (IV) suffers an electrocyclic ring closure to the product 1.2.

An interesting Diels–Alder reaction of azulene with reactive diene tetrachlorothiophene-SS-dioxide, 2.1, afforded benz[a]azulene 2.2 (Scheme 2) [13].

A retro Diels–Alder reaction was used to obtain parent benz[a]azulene 1.3 [14], and Scheme 3 describes the reaction route. The condensation of adduct 3.1 resulted from the addition of benzyne to azulene, with the electron-deficient dienophile 3,6-di(pyridln-2-yl)-1,2,4,5-tetrazine, 3.2, afforded parent azulene 1.3. The condensation step, which involves the strained electron-rich double bond of benzonorbornadiene 6 was followed by a retro Diels–Alder reaction with the elimination of nitrogen and dipyridazine 3.3.

Another synthesis of benz[a]azulene 1.3 reported by Hansen and Sperandio proposed the Heck cyclization of iodobenzene 4.1 as in Scheme 4 [15]. Ring closure catalyzed by Pd(II) to intermediate 4.2 was followed by desulfonylation accomplished with Na₂S₂0₄/NaHC0₃. The Heck procedure will also be encountered in this review for the preparation of other polycondensed azulene compounds.

A large number of substituted benz[a]azulenes obtained by parent compound functionalization or by building the condensed system has been reported. A few representatives from the last category will be listed below. Thus, Sasabe et al. realized the one-pot synthesis of α,β-unsaturated carbonyl derivatives of benz[a]azulenes 5.2 [16], with moderate yields, as shown in Scheme 5, starting from o-(2-furyl)cycloheptatrienylbenzenes 5.1. The transformation was rationalized by the mechanism based on the nucleophilicity of position 2 in furan and on the tendency of this ring to form 1,4-diketones by ring opening, as given in Scheme 5.

After the presentation of a series of syntheses of some azulenes substituted at the 2 position, Wu et al. have produced a series of benz[a]azulenes starting from such compounds 6.1–6.3 [17] via aldol condensation (reactions 1 and 2; products 6.4 and 6.5 in Scheme 6) or Knoevenagel reaction followed by cyclization (reactions 3–5; products 6.6–6.8). A plausible mechanism proposed by the authors for the last reaction sequence is shown in Scheme 6.

A starting material often used in the synthesis of benz[a]azulenic compounds is 2H-cyclohepta[b]furan-2-one and its derivatives, 7.1 [6]. At the same time, its [8 + 2] cycloaddition with enamines is well known and, as will be seen below, widely encountered in the synthesis of benz[a]azulenes. A recent example is that described by Shoji et al. [18] for the obtain benz[a]azulenes 1.3 or 7.6 from 2H-cyclohepta[b]furan-2-one 7.1 and enamine 7.2 in the three-step sequence (Scheme 7). The first step described the generation of intermediate 7.3 through the [8 + 2] cycloaddition. The elimination of the groups CHO and tBu from 7.5 generates the parent or seven-ring substituted benz[a]azulenes 1.3 or 7.6.

2.2. Azulene-Fused Linear Aromatic Hydrocarbons

In addition to the previously illustrated syntheses of benz[a]azulenes, azulene can be condensed with other aromatic cores. Thus, Murai et al. reported an efficient synthesis route for azuleno [2,1-a]naphthalene, 8.3, azuleno [2,1-a]phenanthrene, 8.4, and azuleno [2,1-a]anthracene, 8.5 [19] They coupled with the Suzuki–Miyaura procedure azulen-2-ylboronate and aromatic aldehydes followed by Wittig condensation (Scheme 8). Subsequent bismuth-catalyzed cyclization and aromatization afforded polycyclic aromatic hydrocarbons 8.3–8.5.

Takase et al. involved 2H-cyclohepta[b]furan-2-one 7.1 in the [8 + 2] cycloaddition with enamine 9.1 and 9.4 for building both azulene-naphthalenes (Scheme 9) [20]. The reaction with 9.1 occurred in two steps to 9.3 with moderate yields. The parent azuleno [2,3-a]naphthalene 9.7, an isomer of compound 8.3, had a longer route before it could be obtained. The equilibrium between the two isomers of starting enamine 9.4 afforded a mixture of two cycloaddition products, and only compound 9.5 could be separated and characterized. Next, this intermediary was transformed into the substituted product 9.6 and finally into the azuleno [2,3-a]naphthalene 9.7.

Another series of compounds is represented by azuleno-azulenes and its derivatives. The two azulenes can be cata-condensed on different bonds; however, not all variants were experimentally synthesized. A first experimental attempt started again from 2H-cyclo-hepta[b]furan-2-one, 7.1, which was thermally reacted with 2-(1-pyrrolidinyl)-3-(2,4,6-cycloheptatrienyl)propene, 10.1, and subsequent hydride abstraction and deprotonation resulted in azuleno [1,2-a]azulene, 10.3 (Scheme 10). A longer route, summarized also in Scheme 10, afforded the parent compound 10.4.

Another cata-condensation of two azulenes moieties at the five-membered ring for the preparation of azuleno [1,2-b]azulenes 11.3 was reported by Toda et al. in 1979 by trying to dimerize the allene 11.1 in the presence of DBU [21] (Scheme 11). The result was a mixture from which the target product, in reduced amounts, was separated but fully characterized only a year later [22]. An interesting observation must be made regarding the behavior of azuleno [1,2-b]azulenes structure. The theoretical calculations, as well as several physical properties, suggested that the molecule has a structure with the contributions of two heptafulvene moieties bridged with an etheno-subunit (Scheme 11).

The “enamine” 12.1, rich in electrons at the double bond, reacts with 7.1, affording azulene fused to the five-membered ring, 12.2, as shown in Scheme 12 [23]. The hydrolysis and reaction with morpholine (in the presence of TiCl₄) give the intermediate I, which was treated in situ with methyl propiolate to the adduct 12.3. This adduct was dehydrogenated to azuleno [1,2-b]azulene 12.4 using Pd-C as a catalyst in boiling diphenyl ether.

The following two examples deal with azuleno-azulenes in which the five-membered azulenic ring condenses to a seven-membered ring. Both syntheses have the main step cyclization with fulvenes, developed by Ziegler and Hafner [24,25]. The first procedure, described by Jutz et al. (Scheme 13) [26], introduces fulvene 13.2 in position 1 of azulene 13.1, and the new intermediate fulvene I, after cyclization and elimination of dimethylamine, generates the azuleno [1,2-f]azulene 13.3.

Ziegler–Hafner’s azulene synthesis was also applied by Yoshida et al. starting from cyclopent[e]azulenide 14.3 (the precursor 14.1 and the route to 14.2 will be further detailed). After the transformation of 14.2 in ester mixture 14.3 and reaction with 14.4 followed, the cyclization resulted in azuleno [2,1-e]azulene, 14.6, a new cata-condensed non-alternant tetracyclic hydrocarbon [27]. The pattern aromatic hydrocarbon 14.7 was then generated in the presence of H₃PO₄ (Scheme 14) [28].

The building of the benzene ring as in benz[f]azulene 15.4, which can be defined as an “isomer” of benz[a]azulene, also followed Ziegler–Hafner’s protocol. The condensation of azulene 15.1 with 15.2 afforded the trans isomer of 15.3. The thermic isomerization, subsequent cyclization, and elimination of the dimethylamino group from the intermediate I (Scheme 15) lead to the product 15.4 [29]. Unexpectedly, the benz[e]azulene, 15.6, an isomer of 15.4, could not be synthesized by this route. In this case, the cyclization attacks the five-atom azulene ring, giving the cyclohepta[cd]azulene 15.6.

Several azulene-fused linearly π-extended polycyclic aromatic compounds (azulene-fused PAHs) were obtained recently by Murai et al. [30]. Their attempt to generate the azulene-fused tetracycle dicyclohepta[b,h]-as-indacene, 16.1, on the route 1→2 failed (Scheme 16). The Wittig reaction of 1-formyl-2,2′-biazulene, 16.2 failed due to the stability of tropylium structure 16.2′, which decreased the electrophilicity of the azulene-substituted formyl group. Suzuki–Miyaura coupling between 2-halogenoazulene, 16.5 and 2-Bpin substituted azulene, 16.4 produced almost quantitatively 2,2′-biazulene 16.6. Vilsmeier bis formylation, treatment with p-toluenesulfonyl hydrazine, and subsequent rhodium-catalyzed cyclization gave the product 16.1. Due to the low solubility of 2,2′-biazulene, n-heptyl groups were introduced at the 6-position of the azulene rings in the started azulenes.

Another construction of azulene-fused PAHs described herein refers to the syntheses of two azulene-fused s-indacene isomers, the diazuleno [2,1-a:2′,1′-g]-s-indacene and diazuleno [2,1-a:1′,2′-h]-s-indacene, 17.7 and 17.8 [31]. As in the previous example, the syntheses begin with the Suzuki–Miyaura condensation of pinacoloborane 8.1 with dihalogenated benzenes (step 1 in Scheme 17). However, each benzene molecule possesses two supplementary aldehyde groups, which, under the conditions described in Scheme 17 (step 2), afforded the compounds 17.5 and 17.6, which, after aromatization, provided the target products 17.7 and 17.8. The two aromatic azulene units fused with a central anti-aromatic s-indacene moiety gave the system special physicochemical properties. At acidulation, the obtained dication discloses a local (anti)aromaticity shift driven by the formation of two aromatic tropylium rings described as structures 17.9 and 17.10.

2.3. Azulene-Fused Acenes and Helicenes

The assumption that non-alternant, non-benzenoid π-conjugated polycyclic hydrocarbons exhibit different electronic properties when compared with the all-benzenoid acenes was confirmed by the synthesis and physical properties of several azulene-fused acenes isoelectronic to the all-benzenoid PAHs. Thus, long acenes are highly unstable, whereas the isoelectronic compounds with one or two azulenes placed at the end of the acene backbone are stable. So, the heptacene 18B, obtained by Einholz et al. [32], is very unstable, and the isoelectronic azulene-fused acene, diazuleno [2,1-b:2′,1′-i]anthracene 18A is stable. Recently, Ong et al. succeeded in producing the compound 18.1, a substituted derivative of 18A [33]. The route of its synthesis is shown in Scheme 18. The authors started with the Miyaura–Suzuki coupling in order to build the intermediate 18.3. The condensation with cyclohexane-1,4-dione allowed the “quinone” 18.4, which, in reaction conditions described as step 2, produced the azulene-fused acene 18.1. A similar way to that described for 18.1 was proposed by the authors to obtain acenes with one azulene at the end, 18.7 and 18.8 with the molecular skeleton isomer with pentacene and hexacene. Interestingly, the behaviors of both azulene and acenes were reported for the obtained azulene-fused acenes.

Non-alternant isomers of oligoacenes, namely dibenzo[e,g]azulene, 19.1, benzo [1,2-f:5,4-f′]diazulene, 19.5, benzo [1,2-f:4,5-f′]diazulene, 19.6, and naphtho [2,3-f:6,7-f′]diazulene, 19.7 (Scheme 19) were reported by Wang et al. [34]. Polycyclic hydrocarbon 19.1 was obtained after condensation of 2-bromobenzadehyde with the five-membered ring of 1,2,3,4-tetrakis(4-tert-butylphenyl)cyclopentadiene 19.2 followed by palladium-catalyzed coupling in the reaction conditions described in Scheme 19. The 19.2 and ortho-haloaryl aldehydes, keeping the same reaction route, afforded compounds 19.1 and 19.5–19.7 in good yields.

Azulenohelicenes, which will be presented next, represent a class of compounds somewhat related to the discussed acenes. Yamamoto et al. reported the attainment of starting aldehyde 20.1 [35], which was further used in the Seyferth–Gilbert homologation using the Ohira–Bestmann reagent and potassium phosphate (Scheme 20). Finally, the metal-catalyzed cycloisomerization allowed to [5]helicene frameworks. The last step produces a mixture of azulenohelicenes, 20.3 and 20.4, and helicene, 20.5, in amounts determined by the nature of the catalyst. The geometry of products was largely discussed, and the authors claim that it is the first example of azulene-fused helicene derivatives with unambiguous helical geometry.

Gao et al. published in 2022 [36] a comprehensive paper on [n]helicenes in which one terminal azulene subunit was fused with n-2 benzene rings. After the preparation of the required boronic acid esters, 21.1, these were Suzuki–Miyaura condensed in excellent yields with bromoderivative 21.2 to the intermediates 21.3 and 21.4 Scheme 21. The last step, the cycloisomerization of these intermediates, leads to the products 21.5 and 21.6 with moderate yields. The access to remarkable helicene 21.10 is presented in Scheme 21. Whereas good yields were reported for the Suzuki–Miyaura reaction and the TMS elimination, the subsequent cyclization of 21.9 occurred only in 10% yield. Unfortunately, the target and space of this paper do not allow for a discussion about the interesting geometry of the obtained products.

2.4. Compounds Containing Azulene and One Supplementary Condensed Ring

As specified in the Introduction, the present review proposes a presentation of the syntheses of polycyclic compounds divided into classes of compounds. After examining the synthesis of azulene-containing aromatic condensed hydrocarbons, this chapter is intended to examine compounds with azulene fused with various carbo- or heterocycles with relatively simple structures. The interest in obtaining properties and possible technical uses of such compounds started before the middle of the last century. Therefore, it is not surprising that many of the reported results were already collected in a series of reviews mentioned in the Introduction. Nevertheless, older information in this field was considered current, interesting, and effective and will be reviewed in this chapter.

2.4.1. Azulene Fused with Carbocycles

This subsection begins with the syntheses, which refer to azulenes fused at the five-membered ring, and, as will be seen, most reactions used already mentioned 2H-cyclohepta[b]furan-2-ones, 7.1R. As shown in Scheme 22 and Scheme 23, Takase, Yasunami et al. reported results regarding the obtaining of polycyclic azulenic products starting from 7.1R. The reaction of 6,6-dimethylfulvene, 22.1, with this compound, afforded, depending on the reaction solvent, the product 22.2 or the mixture of 22.2 with 22.3. Treatment of 22.2 with H₃PO₄ gave the polycyclic 22.4 that contains azulene core [37].

Scheme 23 described the reaction of 7.1R with “enamine” 23.1 (rich in electrons at the double bond) performed by the same authors cited above [38]. As a result, several polycyclic derivatives with carbocycle at the five-membered azulene ring, 23.2n, were generated. The compound 23.5, related to the above-described 22.4, was also obtained, as shown in Scheme 23, and the presence of triethylamine produces the isomer 23.6.

Research with remarkable results on the behavior of three benzocyclohepta[a]azulenylium ions 24A, 24B, and 24C, undertaken by Nitta et al., started from the products 24.1–24.3 that were synthesized as shown in Scheme 24 [39]. In order to create these compounds, the authors condensed compound 7.1 with enamines 24.4–24.6. The proposed intermediates have the structure I (depicted for condensation between 7.1 and 24.4). Another observation refers to the enamine 24.6, which exists in equilibrium with 24.6′, of which only 24.6 reacts further with 7.1. Several steps afforded the cations A–C.

A more complex enamine, resulting from the tricyclo [4.3.1.0^1,6]dec-3-en-8-one, 25.1, and pyrrolidine, was reacted with 7.1 to give the bridged compound 25.2 (yield 42%) (Scheme 25) [40,41]. After subsequent protection of the azulene five-membered ring and double bond bromination, two molecules of HBr were eliminated from 25.4X = F₃CCO, affording the compound 25.6X = F₃CCO. An alternative pathway that occurred through steps 3 and 2 replaces the F₃CCO group with CO₂Me, 25.4X = CO₂Me. The ¹H and ¹³C NMR spectra suggest that compound 25.6X = CO₂Me exists in equilibrium between two isomers, 25.6 and 25.7. It is astonishing that the proton elimination from molecule 25.6 leads to two different anions with an extended electronic system, as represented in Scheme 25.

In addition to the procedures for obtaining azulenes fused with carbocycles starting from compound 7.1, other synthesis routes that lead to such products will be described below. In an example (Scheme 26), Takase et al. condensed 1,2-diformylazulene, 26.1, with diethyl acetonedicarboxylate in the presence of triethylamine obtaining 3-oxo-3H-cyclohept[a]azulene-2,4-dicarboxylate, 26.2, in good yield [42]. The hydrolysis and decarboxylation afforded azuleno [1,2-d]tropone 26.3. This compound in concentrated H₂SO₄ exists as the ditropylium cation 26.4. However, protonation with F₃CCO₂H or with diluted H₂SO₄ generates the monocation, hydroxycyclohept[a]azulenylium 26.5, with extended charge and not the tropylium structure 26.6.

In two papers, Takase et al. reported the use of a flash vacuum pyrolytic method to obtain a polycyclic π-conjugated system containing azulene [43,44]. This study started based on the finding that the decarboxylation of compounds 23.6 or 27.5 with 100% phosphoric acid does not give results in the generation of compounds 27.3/27.4 and 27.8. As such, a way to obtain esters from which the CO₂R group was then removed was proposed. The steps of the synthesis, the reaction conditions, and the obtained yields are described in Scheme 27. The Diels–Alder reaction generates the interesting adducts 27.1 and 27.6R, for which subsequent elimination of CO₂Me substituent proceeds with excellent yields. In the final step, the vacuum pyrolysis of 27.2 and 27.7R leads to the target products 27.3 + 27.4 and 27.8R.

In addition to the grafted azulene at the five-membered ring, a series of results have been published regarding the obtaining and properties of azulenes grafted at the seven-membered ring or both azulene rings and some examples are given below.

2,3-Dihydro-1H-cyclopenta[e]azulene, 14.1, was obtained by Jutz and Schweiger starting from enamine 28.1 following Hafner synthesis [45] and then 14.1 was transformed by Yoshida et al. in 1H- and 3H-cyclopenta[e]azulenes, 28.5a and 25.b [46]. The reaction steps, as well as the reaction conditions and obtained results, are shown in Scheme 28. The treatment of this mixture with n-butyllithium leads to the remarkably aromatic stable anion 14.2. The ¹H- and ¹³C-NMR spectra indicate a considerably large peripheral conjugation due to an aromatic electron structure.

Another azulene grafted at the seven-membered ring, 29.3, was generated by the cycloaddition of pentalene 29.1 with cyclooctyne 29.2 at high temperature, as shown in Scheme 29 [47].

Despite their age, the synthesis of some tricyclic compounds, proposed by Hafner et al., should be considered for the elegance of the procedure and the good yields obtained [48]. Scheme 30 describes in detail the pathways that produced the amines 30.2 and 30.7, with the help of which compounds 30.4R, 30.5, or 30.8 were obtained. Some observations are necessary because of the low stability of compound 30.3, and it reacts in situ. The compounds 30.5 and 30.8 can be considered derivatives of pentalene and heptalene, respectively. The last products will be discussed in the next chapter on polycyclic compounds.

After Gibson et al. obtained benzo[cd]azulene-3-ones, 31.2, as described in Scheme 31 [49], Aumüller et al. used the similar tricyclic compound 31.5 in the synthesis of compound 31.7. The compound 31.5 was generated starting from 31.3 and passing through the intermediary 31.4. Then, it was tautomerized to 31.7 via the cation 31.6 with favorable continuous electronic conjugation [50].

2.4.2. Azulene Fused with Heterocycles

Abundant in the literature are studies that describe the obtaining of grafted-heterocyclic azulenes; therefore, only some examples of the synthesis of such compounds will follow to create an image about this subject. The azulene atoms with which a heterocycle is bound to the extra-system are very different, as well as the heteroatoms that can be involved in the grafted system. Thus, at the condensation, two atoms can both participate belonging to the azulene five- or seven-atom ring or one to five- and the other to seven-atom ring, generating an extra-cycle mostly with five or six atoms. Atoms such as oxygen, sulfur, or nitrogen can be present in the extra-system.

In the beginning, some compounds in which the heterocycle contains an oxygen atom will be exemplified, and one of the first papers in the field belongs to Nozoe et al. [51]. Reaction occurred between 7.1CO₂Me and furans 32.1 (Scheme 32); however, with long reaction time and yields of azulenes-fused δ-lactones 32.2 that depend widely on the substitutes of furan.

2-Amino-3-cyano-4-aryl-10-ethoxycarbonylazuleno [2,1-b]pyrans 33.3, and 1,2-dihydro-1-oxabenz[a]azulen-2-ones 33.2 related to the lactones mentioned above, were reported by Wang et al. [52] and Ito et al. [53] using 2-hydroxyazulenes (Scheme 33). Wang performed a three-component reaction between ethyl 2-hydroxyazulene-1-carboxylate, 33.1, aromatic aldehydes, and malononitriles under the influence of DABCO (diazabicyclo [2.2.2]octane) whereas Lewis acid catalyzed condensation of 33.1 with ethyl acetoacetate or ethyl benzoylacetate was achieved by Ito et al. The product yield for the first synthesis is very good, and those obtained after AlCl₃ catalysis depend on the substituents in the starting compounds.

An alternative to the process described by Ito et al. leading with a very good yield to an isomeric lactone, namely 1-ethoxy-4-cyano-5-ethoxycarbonyl-3H-azuleno [1,2-c]pyran-3-one 34.1, was reported by Morita et al. and is shown in Scheme 34 [54].

Lee et al. described the rhodium-catalyzed oxidative [4 + 2] cyclization of azulene carboxylic acids 35.1 with alkynes in the presence of air, as can be seen from Scheme 35 [55]. The reaction pathway involved the C−H activation followed by cyclization reactions of azulene-2-carboxylic acid with acetylenes in the presence of catalysts and oxidants. The number of synthesized products, 35.2 and 35.3, as well as the obtained yields, are remarkable. The same authors realized 3-arylazulenofuranones by iridium-catalyzed sequential C(2)-arylation with intramolecular C−O bond formation from azulenecarboxylic acids 35.4 and diaryliodonium salts [56]. Scheme 35 exemplifies the general reaction route on particular compound 35.5.

In the attempt to generate azuleno [4,5-c]furan, I in Scheme 36, Ebine et al. [57] started from the diester 36.1. However, after the transformations indicated in Scheme 36, the unstable desired compound I was trapped with maleic anhydride as the isomers mixture of cycloadducts 36.3.

Later, Lu et al. obtained adduct 36.5 [58] after bromine elimination with PhLi from 5,6-dibromoazulene, 36.4 affording unstable 5,6-azulyne, intermediate II, the first azulyne to be prepared. This intermediate was trapped with furan, which gave the adduct 36.5. The crystal structure of 36.5 reveals marked bond alternation in the azulene π system (Scheme 36) due to the “isolated” 5,6-double bond by involving it in the newly formed ring.

In continuation of these research studies, starting from compound 36.6, the isomer of adduct 36.5, Payne and Wege succeeded in obtaining compound 36.7 [59]. As Scheme 36 shows, 36,6 was condensed with tetrazine 3.2 to give the intermediate III, which after the cycloreversion step afforded 4-chloroazuleno [4,5-c]furan, 36.7. Azuleno [5,6-c]furan, 36.8, was synthesized by a similar route.

Apart from the oxygen atom, the literature also includes a large number of references dealing with azulenes grafted with the extra-system containing sulfur or nitrogen, and several of these will be selected and presented in the following.

The condensation of 7.1CO₂Me with cyclic enamine containing sulfur reported by Fujimori et al. is described in Scheme 37 [60]. Due to the isomerization of starting dihydrothiophene, 37.1, the condensation leads to the mixture of dihydroazulenothiophenes 37.2 + 37.3. The dehydrogenation of 37.3 produces the azulenothiophene 37.4 with the loss of the electronic azulenic system. The same reaction conditions convert 37.2 in azuleno [1,2-b]thiophene 37.5, which, after elimination of the CO₂Me group, gives the compound 37.6. In continuation of research in this field, the same authors synthesized, in a similar way, azulenes grafted with oxygen or nitrogen heterocycle, 37.7–37.9, with very good or quantitative yields [61].

Azulenes grafted with the extra-system containing sulfur or nitrogen were also reported by You et al. [62]. To provide an approach to azulenes compounds with the extra-system on the seven-membered ring, azuleno [6,5-b]furan 38.3 and azuleno [6,5-b]benzo[d]thiophene 38.5 they used diboron reagent and iodide for palladium-catalyzed [3 + 2] cross-annulation of alkynes 38.1 the other alkynes 38.2 or 38.4 with concomitant aromatic ring expansion. A low amount of homo-annulation products with two substituents nPr and one dibenzo[bd]thiophen-2-yl at the five-membered azulene ring was also reported. The reaction route and the synthesis conditions are described in Scheme 38, and for the reaction development, the authors proposed the “dearomatized” intermediate I.

The failed route for obtaining alkenyl ether 38.6′ (see Scheme 16 [31]) for the preparation of azulene-grafted on the five-membered ring with benzothiophene, 38.7 suggested to Murai et al. the use of its isomer 38.6 and reaction succeeded with an excellent yield as shown in Scheme 38.

An important number of molecules with heterocycles possessing nitrogen attached to azulene were investigated both for scientific interest and for possible practical uses. For example, compounds summarized in Scheme 39 showed potent cytotoxic activity [63]. The iodine substitution from azulene 39.1 with ethynylbenzene afforded a mixture with only 10% cyclized product, 1H-azuleno [2,1-b]pyrrole 39.3. However, the open compound 39.2 can be cyclized to product 39.4 in the conditions described in Scheme 39, with yields largely depending on these conditions.

The reaction of azulen-2-amine with oxalyl dichloride provided azuleno [2,1-b]pyrrole-2,3-dione, 40.2, which after condensation with isatoic anhydrides, 40.3, afforded azuleno [1′,2′:4,5]pyrrolo [2,1-b]quinazoline-6,14-dione, 40.4, in high yield (Scheme 40) [64].

In the article that was intended to obtain benzazulene [30], Jutz and Schweiger also reported the annulation of pyridine to the azulene skeleton as described in Scheme 41. The compound 41.3, obtained from raw materials 41.1 and 41.2, was thermally cyclized, affording the desired azuleno [1,2-b]pyridine 41.4.

Synthesis of azulenophthalimides, in fact, isoindoline-1,3-dione grafted azulenes, 42.3, occurred between 1,2-diformylazulene derivative 42.1 and N-substituted maleimides 42.2 in the presence of PPh₃ (Scheme 42) with good yields [65]. The research was also extended to the production of the more complex compounds 42.4 and 42.5, whose preparation is also shown in Scheme 42. It is worth noting that the authors specify the azulenophthalimides displayed a significant spectral change under electro-chemical reduction conditions.

The recent works of Gao et al. reported the research on the synthesis of azulene-indole fused polycyclic derivatives [66,67], and such systems are promising candidates in the area of organic electronics. For the first step in the proposed synthesis, Miyaura–Suzuki coupling, the authors used borilated and halogenated compounds, with Bpin and halogen-substituted at azulene or the aromatic compound (Scheme 43). In the next step, the nitrene insertion occurred at high temperatures in conditions described in the Scheme and provided annulated compounds with azulene grafted at seven or five-membered rings, 43.6 and 43.7. Scheme 43 also presented, as a curiosity, the obtaining of two linear condensed compounds, 43.10 and 43.14. From these compounds for the last one, seven-membered fused ring systems with 30π electrons, the theoretical calculations as well as photophysical and electrochemical studies suggest a potential use as semiconductors.

Azulene–indoles, 44.3, as novel antineoplastic agents, were prepared by Hong et al. through the synthesis that generates the azulene system (Scheme 44) by microwave-assisted [6 + 4]-cycloaddition of fulvenes 44.1 and α-pyrones 44.2 [68].

Starting from oxalyl chloride but using 4-aminoguaiazulene 45.1 instead of 2-aminoazulene, as in the reaction described in Scheme 40, the cyclization takes place at the five-membered azulenic ring giving lactame 45.2 (Scheme 45) [69]. Another “dicarbonyl” derivative, 45.3, was also condensed with 45.1 to give 45.4.

Among the azulenic tricyclic compounds grafted with a heterocyclic system, the ethyl 1H-azuleno [8,1-cd]-pyridazine-5-carboxylates, 46.3 contain two nitrogen atoms in the condensed ring [70]. The compound was formed after the reaction of a highly efficient substrate for electrophilic substitutions, ethyl 4-ethoxy-3-formylazulene-1-carboxylate 46.1, with hydrazine (Scheme 46). The same reaction using, this time, phenylhydrazine afforded the compound 46.2 with a fulvenic structure. Both reactions occurred with excellent yield.

A target for Gao et al. was to obtain heteroaromatic compounds in which the C=C bond is replaced by B-N, which will have substantially different electronic properties compared with their all-carbon analogs [2,71]. Suzuki−Miyaura cross-coupling was used to afford amines 47.2 and 47.5 (Scheme 47). These intermediates were treated with an excess of phenyl-dichloroborane by using triethylamine as a base, and the products 47.3 and 47.7 were thus generated. The structure of 47.3 replicates as a “BN compound” that of compound 9.2, C=C compound.

Even if it does not fall strictly within the subject of the present chapter, due to the unusual structure and photophysical proprieties of Si-, Ge- and Sn-bridged diazulenylmethyl cations recently published by Murai et al. [72,73], their reported synthesis will be highlighted in Scheme 48 and Scheme 49. The reaction of dichlorodimethylsilane with 2-iodoazulene and the cyclization of precursor diazulenylsilane 48.2 under Vilsmeier formylation conditions occurred with good yields (Scheme 48). The two azulenes, as an electron reservoir in positively charged systems [74], stabilize the cation, and the one-dimensionally π-extended carbocation results due to the Si-bridge.

Starting from dichlorodimethylgermane or dichlorodimethylstannane and 2-iodoazulene, Murai et al. synthesized the compound 49.2 in the same way as described in Scheme 48 for dichlorodimethylsilane. The stability of products decreases in order Si-Ge-Sn.

3. Embedded Azulene Fused Polycyclic Compounds

The previous chapter presented the building of some molecules in which an azulene unit is grafted only on one or two bonds with a wide variety of aromatic or nonaromatic, carbocyclic, or heterocyclic systems. Calling these azulene-embedded structures “oligocyclic” structures, the following chapter includes completely or partially aromatic polycyclic compounds with more extended frameworks that contain the azulene system. This fascinating subject, due to the structural peculiarities of the compounds as well as their potential uses, has concerned a large number of researchers since the second half of the last century and continues to be relevant. Several older and newer results reported in the literature will be developed in this chapter.

3.1. Polycyclic Compounds with One or Two Azulene Moiety in the Molecular Skeleton

The first set of compounds that will be considered refers to the three non-alternant isomers of pyrene with molecules in which azulene is built on pentalene or heptalene skeletons (Scheme 50). As well as pyrene, these compounds have Kekulé structures with a peripheral (4 × 3 + 2)π Hückel system and a central double bond. Remarkably, whereas the azulene core has only one axis symmetry, the compounds A and B with two azulene-containing networks, depicted in Scheme 51, have two axes symmetry as pyrene.

The obtaining of azupyrene, 51.1, proposed by Jutz and Schweiger in 1971, followed the Ziegler–Hafner azulene synthesis and occurred with a very low yield (Scheme 51) [75].

The longer pathway for generation of the same product [76] starts from 7,8,9,9a-tetrahydro-1H-benzo[cd]azulen-6(2H)-one, 52.1, with subsequent building a supplementary five-membered ring to 52.3, benzene ring enlargement with ethyl diazoacetate, hydrolysis, decarboxylation and dehydrogenation over Pd-C (Scheme 52). All steps for this Anderson synthesis proceed with good yields except for the last ones.

Azuleno [2,1,8-ija]azulene, 53.1, can be regarded as a bridged annulene possessing an anthracene perimeter. This compound was obtained by Vogel and Reel in two pathways [77] starting from another bridged annulene, 1,6:8,13-ethanediylidene [14] annulene, 53.2 [78], as shown in Scheme 53. Interestingly, the deprotonation of 53.2 using the known procedure failed. However, the protonation of 53.2, followed by deprotonation, affords the target product 53.1 with a higher yield than the one obtained by the second way, which starts from acid chloride 53.3 [78].

Morita, Takase, et al. continued research on the synthesis of the bridged [14] annulene 53.1 and have achieved a series of such compounds, 53.4, on the routes described in Scheme 53 [79]. Starting from 5H-cyclohept[a]azulen-5-ones, 53.5, the reaction with chloroketene 53.6 was carried out in one or two steps according to the desired substituents. The lactone 53.7, which was formed as an intermediate in the sequence 2–3, was also characterized and, in a reaction with Et₃N, afforded the target compound 53.4.

The concern for this system remained, and in 2023, Morin et al. reported the synthesis of annulated azuleno [2,1,8-ija]azulene, 54.1, using the route shown in Scheme 54 [80]. Condensation of tetrahydropentalene-2,5-(1H,3H)-dione, 54.2, can be carried out with 1,2-thiophendialdehyde when a mixture of syn and anti-isomers of 54.5 was obtained. If one of the CHO groups is protected as in compound 54.3, the syn isomer 54.5 resulted exclusively after a sequence of two aldol condensations. Subsequent nucleophilic addition of lithium TIPS-acetylide followed by a reduction with SnCl₂ and the oxidation of the resulted in 54.6 with DDQ provided the desired thiophene-annulated azuleno [2,1,8-ija]azulene derivative, 54.1, with significant optical properties. The reduction of keto groups in 54.5 and the generation of more electron-rich ether 54.7 occurred with moderate yield; however, the attempts to oxidize this compound failed.

In Scheme 55, are presented for information several compounds with peripheral (4n)π or Hückel (4n + 2)π electrons. Thus, are presented azuleno [8,8a,1,2-def]heptalene system, 55.2, which possesses a Kekulé structure with a peripheral Hückel (4n + 2)π electrons and pentaleno [2,1,6-def]heptalene 55.4 with (4n)π electrons, both obtained by Hafner et al. [81,82]. In the same scheme are included cyclohepta[bc]acenaphthylene, 55.6, with peripheral (4n + 2)π electrons [83] and naphtho [2,1,8-cde]azulene, 55.8, with (4n)π electrons [84]. The starting compounds with which the syntheses were accomplished are included in Scheme 55 but the description of the synthetic pathway of the products was avoided in order not to load the presentation.

Konishi et al. recently studied bis-periazulene derivatives, namely cyclohepta[def]fluorenes, exciting pyrene isomers [85]. As can be seen in Scheme 56, the molecule of these compounds has a structure that can be interpreted as three superimposed electronic distributions. Furthermore, the singlet ground state is in contradiction with theoretical predictions.

The reported synthesis produced the kinetically protected forms of (cyclohepta[def]fluorene) as its triaryl derivatives [86]. Scheme 57 describes the routes that afford the polycyclic molecule 57.6, a precursor for the subsequent generation of desired bis-periazulene derivatives 58.4 found in Scheme 58. The compounds and the reaction conditions, as well as the obtained yields, are included in the schemes.

After the previous concern for the four-cyclic structure, further attention will be paid to more complex polycyclic compounds containing azulene. The benz[a]indeno [1,2,3-cd]azulene, 59.2, (dibenzo derivative of the Hafner’s hydrocarbons, 30.9, discussed above), was synthesized using triptycene, 59.1, via its photoisomer I as intermediate (Scheme 59) [87]. The substituent in position 1 decides the nature of the products and their yield. The protonation takes place at the central double bond in benzylic positions with respect to the two benzo moieties affording the stable tropylium cation, 59.5. Starting from 59.1MeS, along the compound 59.2 the isomers containing the naphthalene skeleton, 59.3 and 59.4, instead of the azulenic moiety are also present.

Next, some examples of azulene-embedded polycyclic aromatic hydrocarbons (PAHs) with a more extended framework were chosen for presentation. Jutz and Kirchlechner [88] and Murata et al. [89] obtained compounds with azulene unit grafted with phenalene at the seven-membered ring, azuleno [5,6,7-cd]phenalen, 60.2, and at the five-membered ring, azuleno [1,2,3-cd]phenalene, 60.4 as described in Scheme 60.

The grafted azulene skeleton with naphthalene both at the five and seven-membered rings, reported by Bestmann and Ruppert, was depicted in Scheme 61 [90]. Wittig condensation between halogenated compound 61.1 and phosphonium salt 61.2 afforded the intermediate I. The hydrolysis, followed by transannular reaction and final dehydrogenation, furnished the product 61.4.

Scheme 62 provides another two transannular reactions, which furnished the naphtho [1,8-ab:4,5_a’b’]diazulene, 62.3 [91], and the above presented azuleno [1,2,3-cd]phenalene, 60.4 [92], the last compound being obtained with a better yield than that reported previously (Scheme 60). The compound 62.3 resulted after transannular reaction and dehydrogenation aroused interest in the distribution of the π-electrons over the entire molecule. The agreement between the calculated and experimental values for electronic transitions shows that the structure of 62.3 should be best represented by completely delocalized structure C.

This section continues with the concern for the azuleno [1,2-a]acenaphthylene, 63.1, and dimethyl acenaphthyleno [1,2-d]heptalene-8,9-dicarboxylate, 63.2 (Scheme 63) both interesting mainly from the point of view of the π electron distribution [93]. The NMR spectra of 63.1 suggest the presence of two-component systems in molecule building, namely one azulenic and another acenaphthylenic rather than one of 20 π electrons. Moreover, the regioselectivity of electrophilic attack in the azulene position 1, producing brominated compound 63.3, indicates the presence of the tropylium ion as an intermediate. The reaction of 63.1 with acetylenedicarboxylic ester produces the [2 + 2] cycloadduct (intermediate I) whose opening leads to 63.2. This is the first example of heptalene condensed with acenaphthylene. The localization of the internal double bond at acenaphthylene was determined based on the NMR spectrum and demonstrates the higher stability of this system compared with the heptalene one.

Murakami et al. applied to 2,2′-di(arylethynyl)biphenyls, 64.1, the approach proposed by Fürstner for metal-catalyzed cycloisomerization of biaryls bearing alkyne units on one of their o-positions [94]. The reported reactions in Scheme 64 [95] involve a skeletal rearrangement in 64.1 in the presence of a Pt^II catalyst and after the cleavage of a highly stable phenyl bond, which expands into a seven-membered ring, resulting in a mixture of polycyclic aromatic compounds. The obtained products have grafted azulene, azuleno [1,2-l]phenanthrenes, 64.2 and 64.4, or grafted naphthalene in the place of azulene, benzo[f]tetraphene, 64.3, 64.5–64.7. The ratio and the obtained yields depend on the phenyl substituent. It is interesting that the exclusive formation of azulene derivative 64.8 is found when the aryl substituent in the raw material is 1-naphthyl.

Another route that starts from alkynes, developed by You et al. [62] and described in Scheme 65, is based on the palladium-catalyzed [3 + 2] annulation technique of alkynes with concomitant aromatic ring expansion driven by a diboron reagent and iodide. The reaction takes place between 2-(pent-1-yn-1-yl)anthracene, 65.1, and oct-4-yne, 65.2 and along with the azulene-fused linear PAHs, 65.3, the homo-annulation products 65.4 with anthracene substituents was also formed.

Tobe et al. reported a remarkable difference in the behavior of compounds with two pairs of ethynyl groups, 1,4,5,8-tetrakis(mesitylethynyl)naphthalene, 66.1 [96] in the reaction in the presence of iodine or with bis(2,4,6-trimethylpyridine)iodine(I) hexafluorophosphate (Scheme 66). The use of the iodine afforded the azulene-embedded PAHs diastereomers mixture, 66.2 and 66.3, and when this was replaced by the above-mentioned reagent, the mixture of diastereomers 66.4 and 66.5 was formed.

The proposed mechanism by the authors for these reactions, described in Scheme 67, was based on the behavior of 1,8-bis(phenylethynyl)naphthalene, 67.1, under the same conditions as those described for the reaction of compound 66.1. The iodinated reagent favored the sequence of reactions with cationic intermediates I⁺–III⁺ and furnished 67.2, whereas the radical pathway was envisaged in the presence of iodine and radical intermediates III–IV were involved in the construction of the azulene moiety.

Among the syntheses used in obtaining azulene-embedded PAHs, Knoevenagel condensation was often used, and a recent procedure was reported by Feng et al. [8]. As described in Scheme 68, the synthesis starts with the Suzuki–Miyaura reaction between boronic esters and halogenated compounds, followed by Knoevenagel condensation. In this way, a large number of products were obtained with an acceptable yield, as summarized in Scheme 68.

Tandem oxidative transannulation between the phenyl and arylethynyl moieties in the 1,8-diphenyl-9,10-bis(arylethynyl)phenanthrenes, 69.1 [97], in the presence of a silver(I) salt as one-electron oxidant, was studied by Konishi, Yasuda et al. (Scheme 69) [98]. The authors believed that a radical cation was generated as an intermediate, which finally afforded the cation 69.2. The subsequent treatment with triethylamine gives hydrocarbon 69.3, in the last two steps with good yields. For steric reasons, the two phenyl substituents are perpendicular to the rest of the molecule. The azulene-embedded polycyclic, non-alternant aromatic hydrocarbon 69.4 is an isomer of benzenoid alternant tribenzo[fg,ij,rst]pentaphene, 69.5.

Narita et al. reported that the first azulene-based chiral helicene with enough energy barrier against the inversion [99], bisazulenoisobenzo-thiophene, 70.4 (Scheme 70). The compound was obtained after Suzuki–Miyaura coupling of dibromo thiophene, 70.1 with boronic ester 70.2, followed by the dimerization of azulenic position 2 in compound 70.3, both reactions occurring with good yields.

The target of the study undertaken by Yamada et al. [100] was to obtain compound 71.1 due to its supposed exceptional dipole created by the two parallel azulene dipoles. However, the Suzuki–Miyaura coupling between 1,8-dibromonaphthalene and boronic azulene ester afforded the mixture of compound 71.2 with smoothly curved helicene-like structure and the spiro [5,6] compound 71.3 (Scheme 71). The helical azulene dimer displays an efficient π-conjugation, and the authors believe that the newly created seven-membered ring could be considered as an equivalent “cycloheptatrienyl anion having the antiaromatic character” and proposed the resonance structures 71A–71.C shown in Scheme 71.

Interesting steric behavior in reactions between different azulene compounds was also observed by Tsuchiya et al. and is described in Scheme 72 [101]. 1,2′-Biazulene bromination and Suzuki–Miyaura coupling with boronic ester 8.1 provide the twisted azulene trimer 72.1, which was then used in two syntheses. The halogenation of this compound and ring-closing (step 2) afforded the compounds depending on the ligand used in the coupling step. With SPhos 1,2′-azulene coupling in 72.1 produced planar 72.2 with “benzene” embedded moiety; however, the presence of DPPF induced 1,8′-coupling and therefore resulted in compound 72.3 with bent “cycloheptatriene” embedded moiety. Another pathway chosen for the transformation of 72.1 was the continuation of the reaction by which this compound was obtained. The result was a mixture of substitution compound 72.4 in a small amount together with the PAH 72.2.

Aromatic diimides have interested chemists as electron acceptors, n-type semiconductors, and chromophores in the visible region [102]; therefore, a series of compounds from this class containing the azulenic system in the molecule has been synthesized recently. Tani et al. fused the azulene boronic ester 8.1 with Br₄NDI (NDI: naphthalene diimide) 73.1, using Suzuki–Miyaura cross-coupling and the obtained intermediate 73.2 was oxidized to tetraazulene-fused tetracene diimide 73.3 (Scheme 73) [103].

New π scaffold materials, dicarboximides of azulene-embedded PHA, were the target of the research undertaken by Würthner et al. After developing the synthesis procedure for terrylene bis imide, 74.1 [104], the palladium-catalyzed annulation reaction was adapted to generation of corresponding 74.4 with azulene moiety in a molecule as presented in Scheme 74 [105]. It is interesting the selective substitution at position 2 of azulene in 74.4 at mild electrophilic bromination by N-bromosuccinimide.

The Suzuki–Miyaura cross-coupling between ester 75.1 bromo derivative 75.2 was also present in the first step of azacoronene synthesis containing azulene subunit 75.6 (Scheme 75) [106]. The reaction of formed intermediate 75.3 with pyrrole 75.4 afforded the precursor 75.5, which, after Scholl reaction in the presence of FeCl₃, produced the target compound 75.6. The presence of a 6-tBu substituent enhances the kinetic and thermodynamic stabilities of azulene moiety. During this study, dication 76.6²⁺ was successfully isolated and characterized by the single-crystal X-ray crystallographic analysis.

Recently, Yan and colleagues reported the construction of the polycyclic system spiro[dibenzo[a,f]azulene-6,2′-indene] 76.4 (Scheme 76). Two 2-arylidene-1,3-indanediones are involved as building blocks in the domino reaction with alkyl or aryl isocyanides in acetonitrile [107]. As can be seen in Scheme 76, the o-position of the former benzylidene group takes part in a formal [5 + 2] cycloaddition to generate a novel dibenzo[a,f]azulene framework procedure reported here for the first time.

Several skeletal generations or modifications of different PAHs using chemical reactions or thermally promoted reactions have been reviewed until now. However, these procedures cannot be used in several complicated skeletal rearrangements, as for the example reported by Sugimoto et al. [108], who performed the reactions on a metal surface using high-resolution noncontact atomic force microscopy. Combining organic synthesis and on-surface cyclodehydrogenation, they have synthesized the isomers diazuleno [1,2-c:2’,1’-g]phenanthrene, 77.5, and diazuleno [1,2-a:2′,1′-c]anthracene, 77.8 (Scheme 77). The strain that exists between the azulene hydrogen atoms in molecule 77.3, obtained as shown in Scheme 77, imposes a highly twisted geometry for this compound. At the same time, molecule 77.8 has a bent geometry that appears due to the hydrogen atoms’ repulsions between these atoms belonging to azulene and anthracene. Both structures were adsorbed flatly onto the Cu(001) surface, and the transformations caused by raising the temperature were studied. At temperature increase, the compound 77.8 does not show any observable changes apart from the gradual destruction of the molecule. The starting 77.3 was transformed as shown in Scheme 77. After the annelation of 77.3 to 77.4, the surface temperature was increased, and several products resulted depending on the used temperature as described in the Scheme. Interestingly, it seems the generation of the azulene isomers, naphthalene and fulvalene, present in PAHs 77.6 and 77.7 for which the authors proposed different obtaining mechanisms. Above 200 °C, the local strain between hydrogen atoms at seven rings in 77.5 was thermally released as the flatter π-system with a fulvaleno moiety, 77.7.

Despite the progress that has been made in the development of polycyclic metallacycles hydrocarbon, seven-membered rings, as well as azulene, were not observed in these systems. That is why it is useful to consider the recent obtaining of such a system by Liu et al. [109]. This study begins with the synthesis of the precursor 78.2 obtained by the [2 + 2 + 1] cycloaddition involving the triple bonds in 78.1 (Scheme 78). The subsequent efficient [5 + 2] annulation between 78.2 and the acetylenic compound 78.3 builds the metal-containing [5 − 5 − 7] scaffold, 78.4. This compound is known as metalla-dual-azulene (MDA) including a metallaazulene and a metal-free organic azulene. The presence of tropylium moiety in 78.4 allowed a number of nucleophilic reactions with the formation of products 78.5, and the [Ir] can be eliminated with nBu₄N⁺F⁻; H₂O producing the compound 78.6 as shown in Scheme 78.

3.2. Several Examples with Azulene Embedded Nanographenes

The last compounds that will be reviewed, especially important for their proven or assumed technical applications, mainly in organic electronics, were included by authors who dealt with them in the class of nanographene [9]. In these compounds, with atomic lattice consisting of a planar hexagonal network of all sp²-hybridized carbon atoms (graphene), structural defects appear as the presence of both a heptagon and pentagon ring or azulene skeleton(s) (not necessarily as azulene moiety). Therefore, one of the aspects studied intensively is represented by the geometry adopted by azulenic nanographene because the introduction of azulene into the graphene network produces more or less intense deviations from the planarity of the network. Being “fashionable” compounds, a large number of researchers had and have as their goal the obtaining, properties, and uses of such PAHs. It is not the purpose of this paper to deal more extensively with this topic but only to give some examples that stimulate interest in this area.

The synthesis of the planar non-benzenoid dicyclohepta[ijkl,uvwx]rubicene, 79.1, reported by Zhang et al., is the first example that will be discussed further [110]. This product, isomer to dibenzo[bc,kl]coronene, 79.2, contains a pentagon and a heptagon that built “formal’’ azulene, which ensures the planarity of the molecule (Scheme 79). The synthesis started from dibenzosuberone 79.3, which, after dimerization, produced compound 79.4. Then, the Scholl reaction and aromatization of intermediate 79.5 afforded the target product 79.1.

Another compound, 80.2, with a similar structure to compound 79.1, with a pair of five and seven-atom condensed rings (“formal’’ azulene), was studied by Würthner et al. [111]. The synthesis of proposed azulenes-embedded PAH 80.2 is described in Scheme 80 and consists of a two-fold palladium-catalyzed [5 + 2] annulation of 3,9-diboraperylene, 80.1 and 1,2-dibromoacenaphthylene. The research results confirmed the negatively curved structure for non-alternant PAH 80.2 containing two fused antiaromatic pentagon and heptagon units with aromatic central benzene. The difference is remarkable compared with nanographene 79.1, which is flat. In contrast to the “parent”80.2, the heptagons and pentagons included in the dication 80.2²⁺ have a weak aromaticity (tropylium behavior) with clockwise diamagnetic ring current alongside the periphery of the half π-conjugated framework with antiaromatic central benzene.

Two embedded azulene in the molecule are also present in the following nanographene 81.6, and the pathway for synthesis of this compound is shown in Scheme 81 [112]. The precursor 81.2 of the desired azulene unit contains α-styryl moiety and suffers the oxidative cyclization to 81.3. The subsequent cross-coupling between 81.3 and triflate 81.1 affords the intermediate 81.4, which, after the Scholl reaction, generates the desired product 81.5. The contiguous 6−7−7−6 ring system in 81.5 instead of the four hexagonal rings in graphene (see Scheme 81) creates a difference between a “narrowed” variant for the azulene cove edge and a normal cove edge for graphene.

In the continuation of the investigations on PAHs in which the graphene geometry is disturbed by structural defects, Liu et al. reported the obtaining and behavior of dicyclohepta[a,g]heptalene-embedded polycyclic conjugated hydrocarbon 82, a structural isomer of bischrysene (Scheme 82) with four contiguous heptagons and two pentagons in the framework (two “formal’’ azulene between two heptagons) [113]. The presence of the four contiguous heptagons forms a “Z” shape in the central π-electron skeleton, and, as a result of the research undertaken by the authors, this incorporation affects the electronic and optoelectronic properties and the chemical reactivity of the compound. The synthesis steps of this compound, as well as the reaction conditions, are depicted in Scheme 82. 2-(2-((4-(Tert-butyl)phenyl)ethynyl)-6-chlorophenyl)azulene, 82.1, was cyclized to 82.2, and subsequent dimerization gave intermediate 82.3. The double Scholl reaction afforded the attempted product 84.4 (an amount of 2% of a partially hydrogenated product with the long name (!): 18,21-bis(4-(tert-butyl)phenyl)-3b,15-dihydro-8,9,10-(epiprop [2]en [3]yl [1,1]diylidene)benzo[a]cyclohepta [6,7] naphtha [2’,1’,8’:3,4,5]azuleno [8,1,2-def]heptalene was also formed).

4. Conclusions

This review summarizes the preparation of embedded azulene polycyclic molecules and tries to cover several areas of this vast chemistry. As can be seen from the content of this review, the syntheses continuously evolved from relatively simple to sophisticated molecules with a series of unexpected properties and practical uses. The described procedures were systematized, taking into account the specific structure of the examined compounds and not the synthetic route used for their generation. After the Introduction, the second Section is assigned to compounds with azulene units grafted only on one or two bonds. The target of this Section is directed toward azulene-fused “oligocyclic” aromatic hydrocarbons, azulene-embedded acenes and helicenes, and azulene fused with carbocycle or heterocycle. The last Section deals with the synthesis of several polycyclic compounds with one or two azulene moieties in the molecular skeleton, as well as several examples with azulene-embedded nanographenes. Instead of the exhaustive exposition of the synthesis procedures, it was preferred to introduce reaction schemes that include the reaction conditions and the yields of the obtained products. Most of the reaction mechanisms for syntheses presented in this review, as well as other related details, have been omitted in order not to load the material, but they are present in the articles included in the references. For systematic information and to highlight progress related to the proposed subject over time, the bibliographic references are focused both on recent information and on several older data.