Azulene Moiety As Electron Reservoir in Positively Charged Systems; A

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Review Review AzuleneAzulene MoietyMoiety asas ElectronElectron ReservoirReservoir inin PositivelyPositively ChargedCharged Systems; A Short SurveySurvey

Alexandru C.C. RazusRazus

Romanian“C.D. Nenitzescu” Academy, Institute “C.D. Nenitzescu” of Organic Chemistry, Institute of Romanian Organic Chemistry, Academy, 202202 BB Spl.Spl. Independentei,Independentei, P.O. Box 35-108, 060023 Bucharest, Romania;Romania; [email protected]@yahoo.com

Abstract: The non-alternant aromatic azulene, an isomer of alternant naphthalene, differs from the latter in peculiar properties. The The large large polarization polarization of the π-electron system over the seven and ﬁvefive rings gives to azuleneazulene electrophileelectrophile property property a a pronounced pronounced tendency tendency to to donate donate electrons electrons to to an an acceptor, acceptor,substituted substituted at azulene at azulene 1 position. 1 position. This This paper paper presents presents cases cases in whichin which azulene azulene transfers transfers electrons electrons to toa suitablea suitable acceptor acceptor as as methylium methylium ions, ions, positive positive charged charged heteroaromatics heteroaromaticsand and examplesexamples ofof neutral molecules that can accept electrons. The proposed product synthesis was outlined and the expected R+ electron transfer was highlightedhighlighted by analyzing the NMR, UV-Vis spectraspectra andand thethe pKpKR values.values.

Keywords: azulene; methylium ion; heteroaromatics; π-electron-electron transfertransfer

1. Introduction The stability stability of of organic organic compounds compounds can can be beincreased increased or lowered or lowered by the by presence the presence of π electronsof π electrons and the and conjugation the conjugation of this of type this of type electron of electron can help can the help stabilization the stabilization of an elec- of antronic electronic system. system. Very briefly Very and brieﬂy as a and general as a generalrule, the rule, stable the aromatic stable aromatic π electronπ electronsystems Citation: Razus,Razus, A.C. A.C. Azulene Azulene systemsneed to needbe coplanar to be coplanar with an with alternating an alternating conjugation conjugation and must and mustfollow follow Huckel’s Huckel’s rule, Moiety as Electron Reservoir in rule,namely namely to contain to contain 4n+2 4n+2π electrons.π electrons. For the For polycyclic the polycyclic aromatic aromatic hydrocarbons, hydrocarbons, the exist- the Positively Charged Systems; A Short Positive Charged Systems; Short existenceence of benzenoid of benzenoid sextets sextets is accepted is accepted as a key as element a key element in the theory in the theoryof aromaticity of aromaticity (Clar’s Survey. SymmetrySymmetry 20212021,, 1313,, x. 526. (Clar’srule) [1]. rule) Thus [1 heptalene]. Thus heptalene (Scheme (Scheme1), the polycyclic1), the polycyclic hydrocarbon hydrocarbon composed composed of two fused of https://doi.org/10.3390/ https://doi.org/10.3390/xxxxx two fused cycloheptatriene rings, despite the alternant conjugation, is an unstable, with a sym13040526 cycloheptatriene rings, despite the alternant conjugation, is an unstable, with a non-planar non-planarhelicity skeleton helicity which skeleton also does which not also satisfy does Huck not satisfyel’s or Huckel’sClar’s rule. or From Clar’s the rule. last From point the of Academic Editor: Anthony Harriman last point of view, pentalene can also be excluded because it has only 4n π electrons. Both Academic Editor: Anthony Harriman view, pentalene can also be excluded because it has only 4n π electrons. Both compounds compounds are rapidly destroyed even at very low temperatures (−78 ◦C to −100 ◦C) [2,3]. Received: 12 March 2021 are rapidly destroyed even at very low temperatures (−78 °C to −100 °C) [2,3]. At the other At the other extreme is found the well-known aromatic planar naphthalene, with alternant Received:Accepted: 1220 MarchMarch 20212021 extreme is found the well-known aromatic planar naphthalene, with alternant conjuga- Accepted:Published: 2024 MarchMarch 20212021 conjugationtion and following and following Clar’s rule. Clar’s rule. Published: 24 March 2021 Publisher’s Note: MDPI stays neu- Publisher’stral with regard Note: MDPIto jurisdictional stays neutral y withclaims regard in published to jurisdictional maps and claims institu- in Pentalene x x publishedtional affiliations. maps and institutional afﬁl- iations.

Naphthalene Copyright: © 2021 by the authors. Azulene Heptalene Submitted for possible open access Copyright: © 2021 by the author. publication under the terms and Licensee MDPI, Basel, Switzerland. Scheme 1. Several bicyclic systems with conjugated π electrons. conditions of the Creative Commons Scheme 1. Several bicyclic systems with conjugated π electrons. This article is an open access article Attribution (CC BY) license distributed under the terms and Azulene is naphthalene’s isomer, built from a fusion of cyclopentadiene and cyclo- (http://creativecommons.org/licenses Azulene is naphthalene’s isomer, built from a fusion of cyclopentadiene and cyclo- conditions of the Creative Commons heptatriene rings. Although this planar compound obeys Huckel’s rule, it possesses a /by/4.0/). heptatriene rings. Although this planar compound obeys Huckel’s rule, it possesses a Attribution (CC BY) license (https:// non-alternant aromatic structure and at ﬁrst glance it lacks aromatic sextet [4,5]. However non-alternant aromatic structure and at first glance it lacks aromatic sextet [4,5]. However creativecommons.org/licenses/by/ when one electron is transferred from the 7-atom ring to the 5-atom ring, the azulene when one electron is transferred from the 7-atom ring to the 5-atom ring, the azulene can 4.0/). can be regarded as the fusion of a 6 π-electron cyclopentadienyl anion and a 6 π-electron

Symmetry 2021, 13, x. https://doi.org/10.3390/xxxxx www.mdpi.com/journal/symmetry Symmetry 2021, 13, 526. https://doi.org/10.3390/sym13040526 https://www.mdpi.com/journal/symmetry Symmetry 2021, 13, x FOR PEER REVIEW 2 of 23

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Symmetry 2021 13 , , 526 be regarded as the fusion of a 6 π-electron cyclopentadienyl anion and a 6 π-electron2 of 21 tropylium cation (Scheme 2). The compound polarity is reflected in the presence of the dipolebe regarded moment as (1.08 the fusionD). of a 6 π-electron cyclopentadienyl anion and a 6 π-electron tropyliumtropylium cationcation (Scheme(Scheme2 ).2). The The compound compound polarity polarity is is reﬂected reflected in in the the presence presence of of the the dipoledipole momentmoment (1.08(1.08 D).D).

Scheme 2. Azulene: resonance structures and orbital molecular. Scheme 2. Azulene: resonance structures and orbital molecular. SchemeReactivity 2. Azulene: studies resonance confirm structures also that and the orbital seven-membered molecular. ring is electrophilic and the Reactivity studies conﬁrm also that the seven-membered ring is electrophilic and five-membered ring is nucleophilic. The electron transfer can be made to a positively the ﬁve-membered ring is nucleophilic. The electron transfer can be made to a positively chargedReactivity substituent studies (Scheme confirm 3). alsoIn this that case, the seven-memberedthe tropylium ion ring generation is electrophilic provides and good the charged substituent (Scheme3). In this case, the tropylium ion generation provides good stabilityfive-membered to the formed ring is cation nucleophilic. and, implicitly, The electr anon activation transfer ofcan the be electrophilic made to a positivelyreactions stabilitycharged tosubstituent the formed (Scheme cation 3). and, In implicitly,this case, the an tropylium activation ion of the generation electrophilic provides reactions good (Scheme 33).). WhileWhile thethe azuleneazulene moleculemolecule isis symmetricalsymmetrical onlyonly withwith respectrespect toto thethe x-axis, naphthalenestability to the is supplementary formed cation and,symmetrical implicitly, with an respect activation to the of ythe-axis electrophilic (Scheme 1). reactions For this naphthalene(Scheme 3). isWhile supplementary the azulene symmetrical molecule iswith symmetrical respect to only the ywith-axis respect (Scheme to1 ).the For x-axis, this reason, azuleneazulene hashas three three pairs pairs of of identical identical positions positions (1,3; (1,3; 4,8; 4,8; 3,7) 3,7) and and two two distinct distinct positions posi- tionsnaphthalene (2 and 6) is while supplementary naphthalene sy mmetricaltwice has four with identical respect topositions the y-axis (α (Schemeand β). These 1). For posi- this (2reason, and 6) azulene while naphthalene has three pairs twice of hasidentical four identical positions positions (1,3; 4,8; (α3,7)and andβ). two These distinct positions posi- tionshave differenthave different charges, charges, therefore therefore different differe reactivity.nt reactivity. In comparison In comparison with other with benzenoidother ben- zenoidtions (2 hydrocarbons, and 6) while naphthalene the difference tw icebetween has four the identical small highest positions occupied (α and βmolecular). These posi- or- hydrocarbons,tions have different the difference charges, between therefore the differe smallnt highest reactivity. occupied In comparison molecular with orbital–lowest other ben- bital–lowestunoccupied molecularunoccupied orbital molecular (HOMO–LUMO) orbital (HOMO–LUMO) ensures its remarkable ensures its chemical, remarkable electronic chemical,zenoid electronic hydrocarbons, or optical the behavior difference [6]. between the small highest occupied molecular or- orbital–lowest optical behavior unoccupied [6]. molecular orbital (HOMO–LUMO) ensures its remarkable chemical, electronic or optical behavior [6].

Scheme 3. Tropylium system involvement as stabilizer. Scheme 3. Tropylium system involvement as stabilizer. As a result of these considerations, this short survey is devoted to the behavior of azulene-1-ylScheme 3. Tropylium moiety assystem electron involvement reservoir as whichstabilizer. inﬂuences several systems that include it. Special attention was given to the synthesis of such interesting systems. The examination of these topics is not exhaustive and is addressed especially to those who want to obtain information on an aspect of the complex chemistry of azulene.

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As a result of these considerations, this short survey is devoted to the behavior of azulene-1-yl moiety as electron reservoir which influences several systems that include it. Special attention was given to the synthesis of such interesting systems. The examination Symmetry 2021, 13, 526 of these topics is not exhaustive and is addressed especially to those who want to obtain3 of 21 information on an aspect of the complex chemistry of azulene.

2.2. Triaryl-methyliumTriaryl-methylium IonIon withwith atat LeastLeast OneOne Azulen-1-ylAzulen-1-yl Moiety Moiety OneOne ofof the best known known and and most most commonly commonly st studiedudied effects effects of of azulen-1-yl azulen-1-yl moiety moiety as aselectron electron donor donor is the is thehigh high stability stability that thatit give its gives to the to attached the attached cation cation generating generating the highly the highlystable pseudo-base, stable pseudo-base, (azulen-1-yl)methylium (azulen-1-yl)methylium ions (Scheme ions (Scheme4), whereas4), from whereas the pK fromR+ = the −6.4 + pKfoundR = for−6.4 triphenylmethyliumfound for triphenylmethylium ion, the value ion, of thethis value parameter of this increases parameter to increases11.5 for the to + + 11.5tri(azulen-1-yl)methylium for the tri(azulen-1-yl)methylium ion [7]. As ioncan [ 7be]. Asseen can in be Scheme seen in 4 Scheme the pK4R the value pK Rincreasesvalue increasesdramatically dramatically with the number with the of number azulen-1-yl of azulen-1-yl at the cation at thecenter. cation Thus, center. the presence Thus, the of + + presencetwo suchof moieties two such ensures moieties a high ensures cation a highstability cation reflected stability by reﬂectedthe pKR by= 7.3. the Introduction pKR = 7.3. Introductionof aryl, heteroaryl, of aryl, but heteroaryl, especially but of especially azulen-1-yl of as azulen-1-yl the third assubstituent the third substituentraises this param- raises thiseter parameterover 10. Therefore, over 10. obtaining Therefore, these obtaining last chemical these last species chemical and speciesthe study and of thetheir study behav- of theirior have behavior been and have continue been and to continue be a concern to be for a concern several forresearch several groups. research groups.

+ Scheme 4. pKR values for some methylium ions. Scheme 4. pKR+ values for some methylium ions. Most synthesis of (azulen-1-yl)methylium ions are based on the reaction of nucle- ophilicMost azulene synthesis with of electrophiles (azulen-1-yl)methylium obtained in io differentns are based ways, on some the reaction of which of willnucleo- be presentedphilic azulene in the with following. electrophiles obtained in different ways, some of which will be pre- sentedThe in carbocation the following. resulting from the protonation of carbonyl double bond (compound 1 in SchemeThe carbocation5) or derived resulting from carbinlos from the (compound protonation2 )of reacts carbonyl with double azulene bond and, (compound depending on1 in the Scheme conditions 5) or used,derived a series from of carbinlos reactions (compound stop at the carbenium2) reacts with salts azulene (step a and, in Scheme depend-5) whileing on others the conditions directly give used, neutral a series product of reactions3 (step a+bstop or at b’). the From carbenium the compounds salts (step3, athe in correspondingScheme 5) while salts others4 are directly synthetized give byneutral hydride product extraction 3 (step with a+b DDQ or b’). (2,3-dichloro-5,6- From the com- + − dicyano-pounds 3,p-benzoquinone) the corresponding in the salts presence 4 are synthetized of HPF6 or, by less hydride often, usingextraction Ph3C withPF DDQ6 (step (2,3- c ordichloro-5,6-dicyano- c’). When azulenesp unsubstituted-benzoquinone) in positionsin the presence 1 and 3of were HPF condensed6 or, less often, with using carbonylic Ph3C+ compounds,PF6− (step c or both c’). When these positionsazulenes unsubstitute can be occupiedd in positions and oligomers 1 and may3 were be condensed also present with in thecarbonylic reaction compounds, mixture, or areboth the these only positions products. can be occupied and oligomers may be also presentAzulenes in the reaction were reacted mixture, with or monoare the oronly diphenyl products. carbinols with the aim to obtain (azulen-1-yl)methane with one or two unsubstituted or substituted phenyl moieties at the central carbon atom (Scheme5)[8–10]. Neither the generation of primary carbocation nor the intermediate azulenium ion were highlighted. The reactions occurred with good yields in acetic acid with the addition of a few drops of H2SO4 and, together with the product substituted in position 1, the reaction mixture contains a reduced amount of 1,3-disubstituted product. The reaction of carbonylic derivatives with azulenes represents and continues to be a constant focus of interest for researchers. Both the scientiﬁc importance and the practical applications of the obtained compounds contribute to this. Several examples will illustrate the synthesis pathways, the nature of the resulting products and some of their properties. The condensation of azulenes with formaldehyde and other aldehydes started in the 1950s–1960s [11]. The early reactions occurred either in ether in the presence of HCl [11] or with HClO4 in acetic acid or in tetrahydrofuran [12]. The latter reaction conditions were applied to reactions of guaiazulene with aryl or heteroaryl aldehydes with good yields (between 20% and 97%), giving perchlorates of (guaiazulen-3-yl)methylium ion with other substituent(s) in positively charged carbon. In attempts with azulene instead of guaiazu-

lene the yield decreased due to a larger or smaller number of formed oligomers or polymers. The presence of di(azulen-1-yl)methane from the azulene-1-carbaldehyde and azulene via perchlorate intermediate was also reported, however without the product characteriza- Symmetry 2021, 13, 526 4 of 21

tion. Here it must be noted that for a long time the absence of elaborate procedures for product characterization (e.g., NMR or MS spectroscopy) has been a serious obstacle to the unequivocal assignment of the structure of some obtained products. This assignment was made mainly on the basis of UV-Vis/IR spectra and elemental analysis. Several reactions of azulene also used benzaldehydes [10] or aliphatic aldehydes and ketones [13]. In 1961 Hafner and al. reacted azulen-1-carbaldehyde and 4,6,8-trimethylazulen-1-carbaldehyde with azulene in the presence of POCl3 followed by treatment with NaI to obtain di(azulen- 1-yl)methylium iodides [14]. The same authors synthesized tri(azulen-1-yl)methylium Symmetry 2021, 13, x FOR PEER REVIEW 4 of 23 chloride (87% yield) after the reaction of azulene with tetra-ethoxy-methane in the presence of HCl in nitromethane.

Scheme 5. General route for the synthesis of azulen-1-yl(s) methylium ions. Scheme 5. General route for the synthesis of azulen-1-yl(s) methylium ions. Systematic research into building and studying the salts of triaryl-methylium ions with oneAzulenes to three were azulen-1-yl reacted with contribution, mono or diphenyl and with carbinols other aryl with or the heteroaryl aim to obtain moieties (az- atulen-1-yl)methane charged carbon, haswith been one undertakenor two unsubstitu especiallyted or by substituted Asao et al. phenyl since 1990 moieties [7,15 ].at Inthe additioncentral carbon to very atom high (Scheme stability 5) achieved [8–10]. Neithe by ther azulen-1-yl the generation moiety of primary mentioned carbocation above [16 nor], anotherthe intermediate target pursued azulenium by the ion authors were was highli theghted. study The of the reactions propeller occurred shaped with structure good which can be adopted by some triaryl-methylium ions, mainly those containing three yields in acetic acid with the addition of a few drops of H2SO4 and, together with the azulen-1-ylproduct substituted moieties atin theposition cationic 1, the center. reacti Theon mixture results obtainedcontains a indicate reduced that amount favorable of 1,3- conjugation contributes to the transition state of the ring ﬂipping as well as to the ground disubstituted product. state. Therefore, these cations show a unique dynamic stereochemical behavior [17–20]. The reaction of carbonylic derivatives with azulenes represents and continues to be The general route for the synthesis of these salts involves two steps: the condensation of a constant focus of interest for researchers. Both the scientific importance and the practical azulene with different aromatic or heteroaromatic aldehydes in acetic acid, followed by applications of the obtained compounds contribute to this. Several examples will illustrate hydride removal from the substituted methane. An example of this reaction sequence is the synthesis pathways, the nature of the resulting products and some of their properties. given in Scheme6 for obtaining methylium salts substituted with three azulen-1-yl moieties, The condensation of azulenes with formaldehyde and other aldehydes started in the 9, or with two azulen-1-yl and phenyl, 10 via neutral intermediates 5 and 7. The hydride 1950s–1960s [11]. The early reactions occurred either in ether in the presence of HCl [11] or with HClO4 in acetic acid or in tetrahydrofuran [12]. The latter reaction conditions were applied to reactions of guaiazulene with aryl or heteroaryl aldehydes with good yields (between 20% and 97%), giving perchlorates of (guaiazulen-3-yl)methylium ion with other substituent(s) in positively charged carbon. In attempts with azulene instead of guaiazulene the yield decreased due to a larger or smaller number of formed oligomers or polymers. The presence of di(azulen-1-yl)methane from the azulene-1-carbaldehyde and azulene via perchlorate intermediate was also reported, however without the product characterization. Here it must be noted that for a long time the absence of elaborate procedures for product characterization (e.g., NMR or MS spectroscopy) has been a serious obstacle to the unequivocal assignment of the structure of some obtained products. This

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+ removal with DDQ gave the expected result, whereas attempts using Ph3P depended + on a neutral compound. Hydride elimination with the help of Ph3P proceedes normally starting from compound 7 but using compound 5 one azulen-1-yl group is substituted by phenyl, leading to product 11 (azulenes 12 and 13 were formed as by-products) [21]. Working with azulene without substituents in position 1 and 3, the azulene can act as a spacer and compounds with the structures 6 and 8 were highlighted in low amounts. In this case, as well as when azulene has a substituent that can be replaced electrophilically (e.g., tBu group) in position 1 and/or 3, the yield decreases due to the formation of oligomers. Symmetry 2021, 13, x FOR PEER REVIEW 6 of 23 Oligomers such as 6A and 8A were converted into bis methylium derivatives, 6B and 8Bb, after hydride(s) removal.

Raz Raz R CPh Raz az 3 C+ C+ H + +

- F6P CPh3 CPh3 Raz 9 11 Raz 12 13

Raz = H, 3-Me, 3-CO2Me + - DDQ/HPF6 Ph3P F6P

Raz R Raz Raz az + - CH CH -2H Raz HC 6B CHO DDQ/ Raz Raz HPF6 in CH3CO2H 6A Raz 5 Raz only when Raz =H; low amount CHO

Raz Rph Rph AzR az Raz R ph CH in - Rph + CH CH -2H CH3CO2H 8B DDQ/ Raz Raz HPF6

Raz = substituent(s) at Raz 8A C3 and/or C7 ring 7 Raz DDQ/HPF6 or Rph = substituent at + - only when R =H; Ph3P F6P az phenyl low amount

Raz C+ Rph - F6P 10 R az Scheme 6. 6.Synthesis Synthesis of of methylium methylium salts salts incorporated incorporated in in azulen-1-yl azulen-1-yl moieties. moieties.

AnotherAnother objectiveobjective pursuedpursued waswas thethe obtainingobtaining ofof asas variedvaried informationinformation asas possiblepossible whenwhen bothboth azuleneazulene andand phenylphenyl moietiesmoieties includedincluded inin thethe methyliummethylium ionion werewere substituted.substituted. Nevertheless,Nevertheless, becausebecause ofof thethe largelarge volumevolume ofof thethe reportedreported data,data, onlyonly somesome ofof thethe mostmost illustrativeillustrative compounds,compounds,9 9,,10 10and and14 14,, will will be be brieﬂy briefly discussed discussed below below (Scheme (Scheme7 ).7).

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Scheme 7. Methylium ions with substituted azulene and/or phenyl moieties. Scheme 7. Methylium ions with substituted azulene and/or phenyl moieties. As mentioned above and as a result of the values for pKR+ collected in Table1,the in-

creasedAs number mentioned of azulen-1-yl above and moieties as a result at the of methylium the values center for pK increasesR+ collected the stabilityin Table of 1,the the systemincreased and number the azulene of azulen-1-yl substituents moieties can decisively at the methylium influence this center parameter. increases Thus, the the stability pKR+ forof the9 (R systemaz = 3-Me) and (Schemethe azulene7) is substituents similar to the can compound decisively without influence substituent this parameter.9 (Raz Thus,= H). However, the large tBu groups in position 3, 9 (R = 3-tBu), increases substantially the the pKR+ for 9 (Raz = 3-Me) (Scheme 7) is similar toaz the compound without substituent 9 pK + and, for the presence of two such groups in positions 3 and 6, 9 (R = 3,6-di tBu), the (RazR = H). However, the large tBu groups in position 3, 9 (Raz = 3-tBu),az increases substan- value exceeds that of the unsubstituted compound by three units. It has been suggested tially the pKR+ and, for the presence of two such groups in positions 3 and 6, 9 (Raz = 3,6- thatdi tBu), this the increase value canexceeds be attributed that of the to unsubstitu the stericted effect compound and less toby hyperconjugationthree units. It has been [16]. Thesuggested contribution that this of theincrease donor can substituents be attributed such to as the OMe steric [22 effect,23] or and NMe less2 [to24 hyperconjuga-,25] to phenyl and/or azulene is more important. As shown in Scheme7, for cation 10 (Rph = Raz = Me2N) tion [16]. The contribution of the donor substituents such as OMe [22,23] or NMe2 [24,25] the charge is distributed between the resonance structures A, A’ and A”, namely methylium, to phenyl and/or azulene is more important. As shown in Scheme 7, for cation 10 (Rph = tropylium, and ammonium ions. Although the contribution of the ammonium group is Raz = Me2N) the charge is distributed between the resonance structures A, A’ and A”, remarkable, it is smaller than that exerted by the tropylium. Thus, the difference between namely methylium, tropylium, and ammonium ions. Although the contribution of the the pK + values of the tri(4-dimethylaminophenyl)methylium ion [26] and that for the ammoniumR group is remarkable, it is smaller than that exerted by the tropylium. Thus, corresponding tri(azulen-1-yl)methylium ion, 9 (Raz = 6-Me2N), namely 9.36 and 24.3, can the difference between the pKR+ values of the tri(4-dimethylaminophenyl)methylium ion be a suggestive example. Therefore, it can be concluded that the extreme stability of the [26] and that for the corresponding tri(azulen-1-yl)methylium ion, 9 (Raz = 6-Me2N), last methylium ion is due to the dipolar structure of the azulene rings, in addition to the namely 9.36 and 24.3, can be a suggestive example. Therefore, it can be concluded that the contribution of the mesomeric effect of the di-methyl-amino groups. extreme stability of the last methylium ion is due to the dipolar structure of the azulene The influence of azulen-1-yl moieties on the positive charge at the cationic carbon rings, in addition to the contribution of the mesomeric effect of the di-methyl-amino is also well reflected by the 13C-NMR spectra in series of compounds 9, 10 and 14. The up-fieldgroups. chemical shifts for C+ belonging to these compounds observed at 151.82–161.38, 161.11–169.83 and 168.58–177.68 ppm, respectively, indicates a decrease in charge at C+ Table 1. pKR+ for the compounds 9, 10 and 14. in the series and an enhanced thermodynamic stability. The chemical shift of C+ in 9 (Raz = 3,6-di tBu) at 151.82 ppm (in DMSO-dRph 6) is slightly up-field comparedpKR+ with those Raz in 9 (Raz = H and Me) at 157.40 andfor 154.1710 and 14 ppm. Considerable9 up-fields10 occur for14 10 (Raz = H andH Me ) at 165.54 and 161.58 ppmH in CDC13)[7,1511.3,16]. It should10.5 be noted3.0 that, despite the3-Me impressive stability of compoundsH 9, 10 and 1411.4with Rph =10.8 Raz = NMe3.72 the 3-tBu - 13.2 - -

Symmetry 2021, 13, x FOR PEER REVIEW 8 of 23

Symmetry 2021, 13, 526 3,6-di tBu H 14.3 12.4 4.67 of 21 6-OMe - >14.0 - - H 4-OMe - 11.7 - 6-OMe 4-OMe - >14.0 - chemical shifts for C+ for these cations (156.44, 162.08, and 169.98 ppm, respectively) are 3,6-di tBu 4-OMe - 13.4 - almost comparable with those with R = Raz = H [25]. H ph4-Me2N - 13.2 - 3,6-di tBu 4-Me2N - 13.8 - Table 1. pK + for the compounds 9, 10 and 14. R H 4-Me2N - - 12.6 3,6-di tBu 4-Me2N - - 13.3 pK + R R for 10 and 14 R az6- Me2N ph - 924.3 10- 14 - 6- Me2N 4-Me2N - 21.5 - H H 11.3 10.5 3.0 6- Me2N 4-Me2N - - 14.0 3-Me H 11.4 10.8 3.7 3-Me (18a) 2-thienyl - 11.2 - 3-tBu - 13.2 - - 3,6-di3-tBu (18a) H2-thienyl 14.3- 12.411.8 4.6 - 6-OMe3-Me (18b) -3-thienyl >14.0- -11.4 - - H3- tBu (18b) 4-OMe3-thienyl -- 11.712.4 - - 6-OMe 4-OMe - >14.0 - 3,6-diThe influencetBu of azulen-1-yl 4-OMe moieties on the - positive charge 13.4 at the cationic carbon - is also wellH reflected by the 4-Me 13C-NMR2N spectra in series - of compounds 13.2 9, 10 and 14. The - up- 3,6-di tBu 4-Me N - 13.8 - field chemical shifts for C+ belonging2 to these compounds observed at 151.82–161.38, H 4-Me2N - - 12.6 161.11–169.83 and 168.58–177.68 ppm, respectively, indicates a decrease in charge at C+ in 3,6-di tBu 4-Me2N - - 13.3 + the series6- Me 2andN an enhanced -thermodynamic stability. 24.3 The chemical - shift of C in -9 (Raz = 3,6-di6- tBu) Me2 Nat 151.82 ppm 4-Me (in DMSO-d2N6) is slightly - up-field compared 21.5 with those in - 9 (Raz = H and6- Me Me)2N at 157.40 and 4-Me 154.172N ppm. Considerable - up-fields occur - for 10 (Raz 14.0 = H and 3-Me (18a) 2-thienyl - 11.2 - Me) at 165.54 and 161.58 ppm in CDC13) [7,15,16]. It should be noted that, despite the 3-tBu (18a) 2-thienyl - 11.8 - impressive stability of compounds 9, 10 and 14 with Rph = Raz = NMe2 the chemical shifts 3-Me (18b) 3-thienyl - 11.4 - + for C3- tforBu (these18b) cations (156.44, 3-thienyl 162.08, and 169.98 - ppm, respectively) 12.4 are almost compara- - ble with those with Rph = Raz = H [25]. Several compounds have also been reported in which phenyl has been replaced by Several compounds have also been reported in which phenyl has been replaced by another aryl or heteroaryl group. In addition to the partially characterized compounds another aryl or heteroaryl group. In addition to the partially characterized compounds reported by Kirby and Reid in 1960 [12], more recently phenyl was replaced with 2- and reported by Kirby and Reid in 1960 [12], more recently phenyl was replaced with 2- and 3-thienyl as in compounds 15a,b depicted in Scheme 8 [27]. These substituents should 3-thienyl as in compounds 15a,b depicted in Scheme8[ 27]. These substituents should have + have a stabilizing effect and, indeed, the chemical shifts+ of C for compounds 15a (Raz = 3- a stabilizing effect and, indeed, the chemical shifts of C for compounds 15a (Raz = 3-Me) Me) and 15b (Raz = 3-Me) at 151.8 and 153.7 ppm, respectively, showed significant up-field and 15b (Raz = 3-Me) at 151.8 and 153.7 ppm, respectively, showed signiﬁcant up-ﬁeld shift compared with those for the corresponding benzyl cations 10 (Raz = 3-Me, Rph = H) at shift compared with those for the corresponding benzyl cations 10 (Raz = 3-Me, Rph = H) at161.1 161.1 ppm. ppm. However, However, despite despite their their stabilizing stabilizing effect, effect, as seen as seenin Table in Table 1, the1, values the values of pK ofR+ belonging to the thienyl compounds are comparable with those of the analogous phenyl pKR+ belonging to the thienyl compounds are comparable with those of the analogous phenylmoiety. moiety.

CO2Me

Raz

+ R C S + N R N C Raz

15a,b 16

a:2-substituted; b:3-substituted thienyl R=Me,Et Raz = 3-Me, 3,6-di tBu

Scheme 8. Methylium ions substituted with heteroaromatic moiety. Scheme 8. Methylium ions substituted with heteroaromatic moiety. Another type of (azulen-1-yl)methylium ion was obtained by the acid catalyzed condensation of methyl 3-formylazulene-1-carboxylate with indoles (Scheme8)[ 28]. The resulting triarylmethanes were oxidized with DDQ to the corresponding azulene-1-yl- + di(indol-3-yl)methylium hexaﬂuorophosphates, 16, with high pKR values (12–14 units), comparable to those of the triazulen-1-ylmethylium ion. Unprotected indoles do not give Symmetry 2021, 13, x FOR PEER REVIEW 9 of 23

Another type of (azulen-1-yl)methylium ion was obtained by the acid catalyzed condensation of methyl 3-formylazulene-1-carboxylate with indoles (Scheme 8) [28]. The re- Symmetry 2021, 13, 526 sulting triarylmethanes were oxidized with DDQ to the corresponding azulene-1-yl-di(in-8 of 21 dol-3-yl)methylium hexafluorophosphates, 16, with high pKR+ values (12–14 units), comparable to those of the triazulen-1-ylmethylium ion. Unprotected indoles do not give clean cleancondensation condensation due to due their to theircapacity capacity to deform to deformylateylate the azulenic the azulenic system. system. Therefore, Therefore, indole indolemust be must substituted be substituted at the atnitrogen the nitrogen atom. atom. InIn addition addition to to the the bis bis methylium methylium ions ions with with azulene azulene as as spacer, spacer,6B 6Band and8B 8B(Scheme (Scheme6 ),6), otherother spacers spacers as as 1,4- 1,4- or or 1,3-phenylene, 1,3-phenylene,17 17or or18 18[ 29[29],], as as well well as as 2,5-thiophenediyl, 2,5-thiophenediyl,19 19and and 2,5-thienothiophenediyl,2,5-thienothiophenediyl,20 20[ 27[27]] were were synthesized synthesized and and studied studied (Scheme (Scheme9). 9). A A special special case case isis represented represented by by the the spectacular spectacular tri-methylium tri-methylium ion ion21 21where where the the positive positive charged charged carbons carbons areare placed placed in in 1,3,5 1,3,5 positions positions of of phenyl phenyl as as spacer spacer [30 [30].].

Raz R Raz R az C+ C+ az C+ C+

R R Raz Raz az az 17 18

Raz = 3-Me, 3,6-di tBu

R Raz Raz S az R + az C+ C + S + C C S

Raz Raz R R 19 az 20 az

Raz = 3-Me, 3,6-di tBu

tBu tBu

tBu C+ tBu tBu tBu

+ C+ C tBu tBu

tBu tBu tBu tBu 21

Scheme 9. Methylium ions substituted at spacers. Scheme 9. Methylium ions substituted at spacers. The special properties such as conductivity and ferro-magnetism of several multistage redoxThe systems special [31 ]properties contributed such to the as desireconductivi to buildty and such ferro-magnetism stable cationic multistage of several redoxmulti- systems by connecting redox systems with an extremely stable carbocation and examining stage redox systems [31] contributed to the desire to build such stable cationic multistage how the redox properties would be changed. In this direction the research must be mentioned which took into account redox properties of the ferrocene and extreme stabilities of the di(1-azulenyl)methylium units [32]. In this aim (Scheme 10) di(azulen-1-yl)ferro-

cenyl-methylium hexaﬂuorophosphate, 22 (R1 = R2 = H or tBu) and 22 (R1 = Me; R2 = H) as well as the di-cation 23 were synthesized. As expected, due to the stabilizing effect of the Symmetry 2021, 13, x FOR PEER REVIEW 10 of 23

redox systems by connecting redox systems with an extremely stable carbocation and examining how the redox properties would be changed. In this direction the research must be mentioned which took into account redox properties of the ferrocene and extreme sta- Symmetry 2021, 13, 526 9 of 21 bilities of the di(1-azulenyl)methylium units [32]. In this aim (Scheme 10) di(azulen-1- yl)ferro-cenyl-methylium hexafluorophosphate, 22 (R1 = R2 = H or tBu) and 22 (R1 = Me; R2 = H) as well as the di-cation 23 were synthesized. As expected, due to the stabilizing effect electronof the electron donor ferrocene donor ferrocene moiety, the moiety, pKR+ ofthe22 pKR+(R1 = of R2 22= H)(R1 slightly = R2 = H) increased, slightly compared increased, tocompared those of the to those phenyl of analogues,the phenyl although analogues, the although chemical the shift chemical for 13C ofshift the for central 13C of cationic the cen- carbonstral cationic of salts carbons22 are of almost salts 22 comparable are almost withcomparable those in with the phenyl those in analogues. the phenyl analogues.

Scheme 10. Di(azulen-1-yl)ferro-cenyl-methylium hexaﬂuorophosphate. Scheme 10. Di(azulen-1-yl)ferro-cenyl-methylium hexafluorophosphate. 3. Charged Hetero-aryls Stabilized by Azulen-1-yl Moieties 3. Charged Hetero-aryls Stabilized by Azulen-1-yl Moieties Two reviews on the synthesis of azulenes substituted with heterocyclic moieties were recentlyTwo published reviews [on33 ,the34]. synthesis Consequently, of azulenes in this su chapterbstituted only with the heterocyclic syntheses of moieties compounds were withrecently charged published heterocycles [33,34]. will Consequently, be brieﬂy examines in this chapter and attention only the will syntheses be paid of to compounds the conse- quenceswith charged of their heterocycles substitution will with be azulen-1-yl briefly exam moieties.ines and attention will be paid to the con- sequencesPyranylium of their salts, substitution which present with azulen-1-yl interesting moieties. properties that make them useful for variousPyranylium technical purposes,salts, which are present stabilized interesting by substitution properties with that electronmake them donating useful for (or var- re- leasing)ious technical groups. purposes, One of the are substituents stabilized by tested substitution for this purposewith electron was azulen-1-yldonating (or moiety releas- situateding) groups. in 2- One or 4-position of the substi towardstuents thetested oxonium for this center purpos ofe pyranylium.was azulen-1-yl The moiety reported situ- azulenyl-pyranyliumated in 2- or 4-position system towards reported the oxonium earlier center described of pyranylium. synthesesfor The 4-(azulen-1-yl) reported azulenyl- 2,6- diphenyl-pyranyliumpyranylium system reported salts [35 ,earlier36]. Chloro-pyranylium described syntheses salt for or 4-(azule even pyranyliumn-1-yl) 2,6-diphenyl- salt were startingpyranylium compounds. salts [35,36]. The obtainedChloro-pyranylium products were salt or characterized even pyranylium by melting salt were points, starting ele- mentalcompounds. analysis The and obtained sometimes products infrared were spectra. characterized In the desire by melting to obtain points, a large elemental and varied anal- numberysis and of sometimes pyranylium infrared salts withspectra. azulene In the moieties desire to as obtain substitute a large and and to varied start from number these of saltspyranylium in the synthesis salts with of azulene pyridines, moieties pyridinium as subs saltstitute or and bis to azulene, start from Razus these et al.salts varied in the bothsynthesis the hetero-cycle of pyridines, and pyridini azuleneum substituents salts or bis azulene, [37]. The Razus reaction et al. route varied and both the the obtained hetero- 4-(azulen-1-yl)pyranyliumcycle and azulene substituents salts are [37]. described The re inaction Scheme route 11 .and Thus, the 4H-pyran-4-ones obtained 4-(azulen-1-1 was reacted with PCl5 or POCl3 and perchloric acid. When Raz = Ph the intermediate 2 was separated and characterized whereas for Raz = Me the reaction was continued without separation of unsTable2. The redoubtable nucleophilicity of azulene chlorine leads to substitution yields ranging from satisfactory to very good. Scheme 11 shows that the obtained pyranylium salts have various substituents at azulene and the 2 and 6 positions of Symmetry 2021, 13, x FOR PEER REVIEW 11 of 23

yl)pyranylium salts are described in Scheme 11. Thus, 4H-pyran-4-ones 1 was reacted with PCl5 or POCl3 and perchloric acid. When Raz = Ph the intermediate 2 was separated and characterized whereas for Raz = Me the reaction was continued without separation of Symmetry 2021, 13, 526 10 of 21 unstable 2. The redoubtable nucleophilicity of azulene chlorine leads to substitution yields ranging from satisfactory to very good. Scheme 11 shows that the obtained pyranylium salts have various substituents at azulene and the 2 and 6 positions of the heterocycle are thesubstituted heterocycle with are phenyl, substituted methyl, with thiophen-2-yl phenyl, methyl, or furan-2-yl. thiophen-2-yl Position or furan-2-yl. 3 in the heterocycle Position 3 inwas the also heterocycle occasionally was alsosubstituted. occasionally substituted.

Scheme 11. Synthesis of 4-(azulen-1-yl)pyranylium salts. Scheme 11. Synthesis of 4-(azulen-1-yl)pyranylium salts. Table 2. 1H-NMR spectra of substituted azulenic compounds (chemical shifts in ppm). The beneficial effect on the pyranylium ring salt stability can also be exerted by the azulen-1-yl1-Phenyl- moiety placed4-(Azulen-1-yl)- in position 2 of the ring as in products 8, 9. The reaction started 1H Azulene Salt 3 a Salt 5 b Salt 10 c fromazulene 2H-pyran-2-one2,6-diphenylpyridine and occurred as shown in Scheme 12 with good yields when R = Ph 30/50H -(36–45%) - and only with 17% 7.95 for R = Me [37,38]. 8.83 8.06 8.32 2 7.81 8.02 8.18 8.92 8.45 8.18 3 7.30 7.43 7.53 7.77 7.51 7.35 4 8.23 8.34 8.44 8.89 8.65 8.44 5 7.05 7.14 7.28 8.03 7.77 7.28 6 7.45 7.58 7.45 8.31 8.07 7.72 7 7.05 7.14 7.29 8.14 7.80 7.29 8 8.23 8.55 8.71 9.57 9.12 8.71 a b c R3 = Raz = H; R2 = Ph. R3 = Raz = H; R2 = Me. Raz = H; R2 = Ph; Rpy = nBu.

The beneficial effect on the pyranylium ring salt stability can also be exerted by the azulen-1-yl moiety placed in position 2 of the ring as in products 8, 9. The reaction started from 2H-pyran-2-one and occurred as shown in Scheme 12 with good yields when R = Ph (36–45%) and only with 17% for R = Me [37,38]. SchemeThe 12. pyranylium Synthesis of salts 2-(azulen-1-yl)pyranylium were then used as valuable salts. synthons for obtaining a series of pyridines and pyridinium salts [34]. The general pathway for the synthesis of pyridinium salts in two steps [39] was applied to the generation of salts substituted with azulen-1- yl moieties (Scheme 13)[38,40,41]. In the first step the pyranylium ring is opened by amine in the presence of triethylamine followed by the ring closure of the intermediate enamine. Good or even quantitative yields were reported for products 10, 100 and 11, 12 and the generation of pyridinium salts is not influenced by the amine except when tBuNH2 was used, which lowers the yield. When started from 2,6-dimethylpyranilium Symmetry 2021, 13, x FOR PEER REVIEW 11 of 23

yl)pyranylium salts are described in Scheme 11. Thus, 4H-pyran-4-ones 1 was reacted with PCl5 or POCl3 and perchloric acid. When Raz = Ph the intermediate 2 was separated and characterized whereas for Raz = Me the reaction was continued without separation of unstable 2. The redoubtable nucleophilicity of azulene chlorine leads to substitution yields ranging from satisfactory to very good. Scheme 11 shows that the obtained pyranylium salts have various substituents at azulene and the 2 and 6 positions of the heterocycle are substituted with phenyl, methyl, thiophen-2-yl or furan-2-yl. Position 3 in the heterocycle was also occasionally substituted.

Symmetry 2021, 13, 526 11 of 21 Scheme 11. Synthesis of 4-(azulen-1-yl)pyranylium salts.

The beneficial effect on the pyranylium ring salt stability can also be exerted by the saltsazulen-1-yl alongside moiety the placed pyrylium in position salts 13 2, of traces the ring of anilinesas in products14 were 8, 9 present. The reaction in almost started all Symmetry 2021, 13, x FOR PEER REVIEWreactionsfrom 2H-pyran-2-one with amines; and however, occurred using as ishownPrNH2 inthe Scheme amount 12 of with aniline good reaches yields a when 5–25%12 R yield. of= Ph23

The(36–45%) route and for generationonly with 17% of compound for R = Me14 [37,38].is described in Scheme 13.

The pyranylium salts were then used as valuable synthons for obtaining a series of pyridines and pyridinium salts [34]. The general pathway for the synthesis of pyridinium salts in two steps [39] was applied to the generation of salts substituted with azulen-1-yl moieties (Scheme 13) [38,40,41]. In the first step the pyranylium ring is opened by amine in the presence of triethylamine followed by the ring closure of the intermediate enamine. Good or even quantitative yields were reported for products 10, 10′ and 11, 12 and the generation of pyridinium salts is not influenced by the amine except when tBuNH2 was used, which lowers the yield. When started from 2,6-dimethylpyranilium salts alongside the pyrylium salts 13, traces of anilines 14 were present in almost all reactions with amines; however, using iPrNH2 the amount of aniline reaches a 5–25% yield. The route

forScheme generation 12. Synthesis of compound of 2-(azulen-1-yl)pyranylium 14 is described in salts.Scheme 13. Scheme 12. Synthesis of 2-(azulen-1-yl)pyranylium salts.

Raz Raz Raz AcOH RpyNH2 /Et3N

R + R R2 R2 + 2 O 2 R2 N R2 - NHR ClO4 Py O - Rpy ClO4 3-7 10-12

10: R2 =Ph 11: R3 =H;R2 = thiophen-2-yl Rpy = nBu Raz =H,4,6,8-Me3,5-iPr,3,8-Me2 Raz = H, 3-Me, 4,8-Me2, 4,6,8-Me3, Rpy = nBu 2-tBu,6-Me, 5-iPr,3,8-Me2 10': R2 =Ph 12: R3 =H;R2 = furan-2-yl Rpy =H,Me,iPr, Bn, tBu, Ph Raz = H, 4,6,8-Me3,5-iPr,3,8-Me2 Raz =H Rpy = nBu

Raz Raz Raz -H2O +

Me N+ Me Me NHiPr Me NHiPr H C iPR O 3 ClO - 14 13 4

Raz = H, 4,6,8-Me3,2-tBu,6-Me

Scheme 13. Synthesis of 4-(azulen-1-yl)pyridinium salts. Scheme 13. Synthesis of 4-(azulen-1-yl)pyridinium salts. Research has also been pursued on oxygen replacement from 2,4-diphenylpyranylium Research has+ also been pursued on oxygen replacement from 2,4-diphenylpyranyl- salts, 8, with N Rpy, just as for 2.6-pyranilium salts (Scheme 14). The yields of products 15 ium salts, 8, with N+Rpy, just as for 2.6-pyranilium salts (Scheme 14). The yields of products were very good except when Rpy = Ph (yields: 26–34%) [38]. 15 were very good except when Rpy = Ph (yields: 26–34%) [38].

Symmetry 2021, 13, x FOR PEER REVIEW 13 of 23

SymmetrySymmetry 20212021,,13 13,, 526x FOR PEER REVIEW 1312 of 2123

Ph Ph Raz Raz Ph 1. R NH /Et N Ph R py 2 3 R + az + az Ph O 2. AcOH Ph N - 1. RpyNH2 /Et3N ClO4 Rpy - + + ClO4 Ph O 2. AcOH Ph N 8- 15 ClO4 Rpy - ClO4 815; Raz = H, 3-Me, 4,6,8-Me3, 5-iPr,3,8-Me152 Rpy = iPr, Bn, Ph 15; Raz = H, 3-Me, 4,6,8-Me3, 5-iPr,3,8-Me2 R = iPr, Bn, Ph Scheme 14. Synthesispy of 2-(azulen-1-yl)pyridinium salts.

Scheme 14. Synthesis of 2-(azulen-1-yl)pyridinium salts. SchemeIn 14.addition Synthesis to ofthe 2-(azulen-1-yl)pyridinium research on pyranylium salts. and pyridinium salts with phenyl or methyl Inat additionpositions to 2 theand research 6, these on positions pyranylium were and also pyridinium replaced by salts 5-membered with phenyl heterocycles, or methyl atthiophen-2-yl positionsIn addition 2 and to thefuran-2-yl 6, these research positions as on shown pyranylium were for compounds also and replaced pyridinium 12 byand 5-membered 13salts in Schemewith phenyl heterocycles, 11 [42]. or me-The thiophen-2-ylthylability at positions to donate and 2 electronsand furan-2-yl 6, these of as positionsazulen-1-yl shown for were mo compounds alsoiety replacedsuggested12 and by the 5-membered13 ideain Scheme of stabilizing heterocycles, 11[ 42]. posi- The abilitythiophen-2-yltively tocharged donate and heteroaromatic electrons furan-2-yl of azulen-1-yl as compounds, shown for moiety compounds not suggested only with 12 the oneand idea of13 this ofin stabilizingScheme group but 11 positively [42].with Thesev- chargedabilityeral azulen-1-yl to heteroaromatic donate groups.electrons compounds,Because of azulen-1-yl the attempts not mo onlyiety to with suggestedobtain one 2,4,6-tri(azulen-1-yl)pyranylium of thisthe groupidea ofbut stabilizing with several posi- azulen-1-yltivelysalts werecharged unsuccessful, groups. heteroaromatic Because attention the compounds, attempts was directed to not obtain only to the 2,4,6-tri(azulen-1-yl)pyranylium with synthesis one of ofthis some group of theirbut with vinylogs saltssev- wereeral[43]. azulen-1-yl unsuccessful,Thus, the groups.synthesis attention Because started was the directed from attempts 2,6-dimethyl-4-(azulen-1-yl)pyranylium to the to synthesisobtain 2,4,6-tri(azulen-1-yl)pyranylium of some of their vinylogs salts [43 or]. Thus,saltsfrom were the2,4,6-trimethylpyranylium synthesis unsuccessful, started attention from 2,6-dimethyl-4-(azulen-1-yl)pyranylium salts was whichdirected are to condensed the synthesis with of azulene-1-carbaldehyde some salts of their or from vinylogs 2,4,6- trimethylpyranylium[43].(Scheme Thus, 15). the synthesis salts whichstarted are from condensed 2,6-dimethyl-4-(azulen-1-yl)pyranylium with azulene-1-carbaldehyde (Scheme salts 15 or). from 2,4,6-trimethylpyranylium salts which are condensed with azulene-1-carbaldehyde (Scheme 15).

Scheme 15. Viny-logs of tri(azulen-1-yl)pyranylium salts. Scheme 15. Viny-logs of tri(azulen-1-yl)pyranylium salts.

The reaction of salts 5 with azulene-1-carbaldehyde (AzCHO) occurred in acetic anhy- drideSchemeThe and 15.reaction a mixture Viny-logs of of salts productsof tri(azulen-1-yl)pyranylium 5 with16 azulene-1-carbaldehydeand 17 resulted, depending salts. (AzCHO) on the reactionoccurred temperature. in acetic an- Athydride 100 ◦C and mono a mixture condensation of products generates 16 and product 17 resulted,17 at about depending 50% and on the16 resulted reaction in temper- trace, The reaction of salts 5 with azulene-1-carbaldehyde (AzCHO) occurred in acetic an- whereasature. At at 100 reﬂux °C mono after biscondensation condensation, generates the amount product of 17 compound at about 50%16 increased and 16 resulted to about in 45%hydridetrace, and whereas and17 decreased a mixture at reflux toof after 5–10%.products bis Aco 16 similarndensation, and 17 behavior resulted, the amount was depending reported of compound on when the reaction 2,4,6- 16 increased trimethyl- temper- to pyranyliumature.about At 45% 100 and perchlorate °C mono17 decreased condensation reacted to with5–10%. generates AzCHO. A similar product At 100behavior◦ 17C onlyat wasabout compound reported 50% and when20 16resulted, resulted 2,4,6- tri- atin 160trace,methyl-pyranylium◦C whereas compound at reflux20 perchloratedisappears after bis coreacted beingndensation, replacedwith AzCHO. the by amount compounds At 100of compound °C 18onlyand compound 1619, increasedand under 20 re-to microwaveaboutsulted, 45% at 160 and irradiation °C 17 compound decreased salt 18 20toremained disappears5–10%. theA similar onlybeing product replacedbehavior (50–55%). bywas compounds reported when 18 and 2,4,6- 19, andtri- methyl-pyranyliumunderRecently, microwave this classirradiation perchlorate of compounds salt reacted 18 remained has with been AzCHO. the expanded only Atproduct by100 the °C (50–55%). generation only compound of 4-(azulen- 20 re- 1-yl)sulted, pyranylium at 160 °C compound and pyridinium 20 disappears salts substituted being replaced in 2- and by 6-positionscompounds with 18 and 2-(furan-2- 19, and yl)vinyl,under microwave 2-(thiophene-2-yl)vinyl irradiation salt or 18 2-(3-thienyl)vinyl remained the only moieties product [44 (50–55%).].

Symmetry 2021, 13, x FOR PEER REVIEW 14 of 23

Symmetry 2021, 13, 526 Recently, this class of compounds has been expanded by the generation of 4-(azulen-13 of 21 1-yl) pyranylium and pyridinium salts substituted in 2- and 6-positions with 2-(furan-2- yl)vinyl, 2-(thiophene-2-yl)vinyl or 2-(3-thienyl)vinyl moieties [44]. The distribution of π electronselectrons resultingresulting fromfromresonance resonance structures structures of of charged charged hetero- heter- cyclesocycles substituted substituted in in position position 4 with4 with azulen-1-yl azulen-1-yl moiety, moiety, shown shown in Scheme in Scheme 16, significantly 16, signifi- influencecantly influence the chemical the chemical shifts shifts of 1H of and 1H and13C 13 inC thein the NMR NMR spectra spectra of of both both azuleneazulene andand heterocycle moieties moieties of of the the salts. salts. Because Because prot protonon spectra spectra of the of the studied studied salts salts (Table (Table 2) are2) aremore more suggestive suggestive in this in regard this regard and provide and provide more morevaluable valuable information, information, they will they be willbriefly be brieflydiscussed. discussed.

R + Raz az

R3 R3

+ R2 X R2 R2 X R2 + + + X =O or Rpy-N Scheme 16. The most important resonance structures ofof chargedcharged heterocycles.heterocycles.

TableFrom 2. 1H-NMR Table 2spectra it can of be substituted seen that theazulenic good compounds electron-acceptor (chemical pyranylium/pyridinium shifts in ppm). moiety strongly de-shielded all azulenic protons compared with neutral 1-phenylazulene [45] 1-Phenyl- 4-(Azulen-1-yl)- or with1H 4-(azulen-1-yl)-2,6-diphenylpyridineAzulene [41]. On the otherSalt hand, 3 a theSalt donor-electron 5 b Salt 10 c azulene 2,6-diphenylpyridine contribution of azulene can be highlighted by comparing the chemical shift of protons in 3′/5′H - - 7.95 8.83 8.06 8.32 the pyranylium ring of compounds 3 and 5 (δ = 8.83 and 8.06 ppm, respectively) and for the 2 7.81 8.02 8.18 8.92 8.45 8.18 same protons in 2,4,6-triphenyl-pyranylium perchlorate (δ = 9.17 ppm) [46,47]. 3 7.30 7.43 7.53 7.77 7.51 7.35 The dihedral angle determines the intensity of the push-pull effect between the hete- 4 8.23 8.34 8.44 8.89 8.65 8.44 rocycle and the aromatic groups as well as the direction of the magnetic ﬁelds generated 5 7.05 7.14 7.28 8.03 7.77 7.28 by the heteroaromatic ring current, well reﬂected in the 1H-NMR spectra. For this reason, 6 7.45 7.58 7.45 8.31 8.07 7.72 the dihedral angle was calculated [48] for several (azulen-1-yl)heteroaromatic systems and 7 7.05 7.14 7.29 8.14 7.80 7.29 results8 are included8.23 in the 8.55 Table 3[ 37]. The data 8.71 in the table highlight 9.57 some9.12 features8.71 of these systems. The angle for neutral 4-azulen-1-yl-2,6-diphenylpyridine exceeds by 16o a R3 = Raz = H; R2 = Ph. b R3 = Raz = H; R2 = Me. c Raz = H; R2 = Ph; Rpy = nBu. that of corresponding pyridinium salt 10 (R2 = Me; Rpy = nBu; Raz = R3 = H) attesting the contributionFrom Table of higher 2 it can conjugation be seen that between the good the electron-acceptor two moieties for salt.pyranylium/pyridinium moiety strongly de-shielded all azulenic protons compared with neutral 1-phenylazulene Table 3. Dihedral angle between the azulen-1-yl and the charged heterocycle moiety. [45] or with 4-(azulen-1-yl)-2,6-diphenylpyridine [41]. On the other hand, the donor-elec- ◦ tron contributionCompd. *of azulene can be R highlightedaz by comparingR3 theDihedral chemical Angle shift (in of)[ protons48] in the pyranylium ring of compoundsH 3 and 5 (δ = H 8.83 and 8.06 ppm, respectively) 24 and for the same3 (R2 protons= Ph) in 2,4,6-triphenyl-pyranyliumH Me perchlorate (δ = 9.17 ppm) 38 [46]. The dihedral angle determines2-tBu-6-Me the intensity of H the push-pull effect between 50 the heterocycle and the aromatic groups asH well as the direction H of the magnetic 22fields generated 5 (R2 = Me) by the heteroaromatic ring current,2-tBu-6-Me well reflected in H the 1H-NMR spectra. 45 For this reason, H H 29 the dihedral10 (R angle= Me; was calculated [47] for several (azulen-1-yl)heteroaromatic systems and 2 H Me 42 R = nBu) results arepy included in the Table2-t Bu-6-Me3 [37]. The data in H the table highlight some 54 features of o these10 (Rsystems.2 = Ph; RThepy = angle Me) for neutral H 4-azulen-1-yl-2,6-diph Henylpyridine 39 exceeds by 16 *that For 4-azulen-1-yl-2,6-diphenylpyridineof corresponding pyridinium the salt dihedral 10 (R angle2 = Me; = 45◦ .Rpy = nBu; Raz = R3 = H) attesting the contribution of higher conjugation between the two moieties for salt. The involvement of the charged heteroaromatic moiety decreases from pyranylium to pyridinium salts due to the releasing electron effect, +I, of alkyl substituent at quaternary nitrogen. As a result, the resonance structure with tropylium system Scheme 16 decreases in contribution and so the dihedral angle increases followed by the deshielding of pyridinium protons and the shielding of azulene protons for pyridinium salts 10 in order of inductive + effect of substituent Rpy at N , namely iPr < nBu < Bn < Ph. Another disturbing factor of the dihedral angle is the occupation of the azulenic position 2 or of position 3(5) of the heterocycle. As an example, the presence of tBu at C2 in salts 3 or 5 with RAz = 2-tBu,6-Me shielded azulenic protons and de-shielded pyranylium protons, and the Me in position 3 of pyranylium moiety shields all azulenic protons. Symmetry 2021, 13, 526 14 of 21

There are no significant differences between the chemical shifts of azulene protons for the pyranylium and pyridinium salts with thiofen-2-yl or furan-2-yl in 2 and 6-positions, 6, 7, 12 and 13 and those of the corresponding compounds with phenyl in these positions [42]. Without going into details, a remark must be made regarding the influence of the heteroaromatic magnetic field, which exerts influence mainly on the neighboring azulene protons 2, 7 and 8, which are more deshielded [40,41]. As expected, the chemical shifts of carbon atoms belonging to azulene for all salts included in the pyranylium and pyridinium series 3–13 undergo an important deshielding as compared with the reduced effect when azulene is coupled with milder electron withdrawing heterocycles, such as pyridines, thiophene or with phenyl an (effect present especially at C5, C7 and C8a where an increase to 12 ppm was observed for chemical shifts) [37]. With the decrease of push-pull efficiency exerted by the π-electronic system at the increase in dihedral angle, a bathochromic effect results, observed in UV-Vis spectra in the order: pyridines, pyridinium salts, pyranylium salts [37,38,40,41]. The values of λmax (in methanol) for these compounds with Raz = R3 = H; R2 = Ph (Rpy = Me) are 370, 434 and 530 nm, respectively. The stabilization of tropylium structure by alkylation produces a bathochromic displacement; for example, for pyranylium salts 3 (Raz = H), 3 (4,6,8-Me3) or 3 (5-iPr,3,8-Me2) λmax increases in the order: 530, 543 and 576 nm. As an interesting observation, for the 2,4,6-tri(azulen-1-ylvinyl) pyranylium salt 18, due to the very large conjugation of the π-electronic system, λmax reaches a high value, 690 nm [43]. The research on charged heteroaryls stabilized by azulen-1-yl moieties was recently enlarged with a new class, namely chalco-geno-pyranylium salts with 4-position occupied by azulen-1-yl group [49]. 4-(azulen-1-yl)-2,6-diphenyl-thiopyranylium and 4-(azulen-1- Symmetry 2021, 13, x FOR PEER REVIEW 16 of 23 yl)-2,6-diphenyl-selenopyrylium perchlorates, 21 and 22 (Scheme 17) were synthesized with good yields on the same route as that used for the corresponding pyranylium salts.

Scheme 17. 4-(Azulen-1-yl)chalco-geno-pyranylium salts.salts.

The lowerlower chalco-geno-pyrylium chalco-geno-pyrylium salts’ salts’ polarization polarization compared compared with that with for thethat pyrylium for the saltspyrylium is reflected salts is both reflected in UV-Vis both in spectra UV-Vis as wellspectra as inas thewell proton as in the chemical proton shifts. chemical Thus, shifts. the + + + bathochromic effect noticed in order O < S < Se+ (λ+ for+ 3 (R = R = H; R = Ph), Thus, the bathochromic effect noticed in order O < S max< Se (λmax foraz 3 (R3az = R3 =2 H; R2 = 21 (R = H and 22 (R = H) are 530, 572 and 600) could be associated with the decrease Ph), 21az (Raz = H and 22az (Raz = H) are 530, 572 and 600) could be associated with the decrease 1 inin thethe electronegativityelectronegativity ofof heteroatomheteroatom (O,(O, 3.5;3.5; S,S, 2.5;2.5; Se,Se, 2.4)2.4) [[49].50]. TheThe 1H-NMRH-NMR spectraspectra ofof chalco-geno-pyrylium salts salts show show the the same same characteristics characteristics and and trends trends as in as the in case the presentedcase pre- abovesented for above pyranylium for pyranylium salts. salts. 4. Other Systems Stabilized by Azulen-1-yl Moieties 4. Other Systems Stabilized by Azulen-1-yl Moieties In this last section reference will be made to some special cases of azulen-1-yl moiety In this last section reference will be made to some special cases of azulen-1-yl moiety participation in the stability of some carbocations and even of some neutral molecules. participationIn connection in the withstability the stabilizationof some carboc ofations triarylmethylium and even of ionssome by neutral at least molecules. one azulen- 1-yl moietyIn connection discussed with before, the stabilization the delocalized of tria mono-carbeniumrylmethylium ions ions, by salt at least23, stabilized one azulen- by largely1-yl moiety conjugate discussedπ electrons before, the including delocalized azulen-1-yl mono-carbenium moieties, isions, presented. salt 23, stabilized Salt 23 was by obtainedlargely conjugate by condensation π electrons ofall-trans-retinal including azulen-1-yl with azulenes moieties, (Scheme is presented. 18)[51 Salt]. 23 was obtained by condensation of all-trans-retinal with azulenes (Scheme 18) [50].

Scheme 18. Condensation of all-trans-retinal with azulenes.

Symmetry 2021, 13, x FOR PEER REVIEW 16 of 23

Scheme 17. 4-(Azulen-1-yl)chalco-geno-pyranylium salts.

The lower chalco-geno-pyrylium salts’ polarization compared with that for the pyrylium salts is reflected both in UV-Vis spectra as well as in the proton chemical shifts. Thus, the bathochromic effect noticed in order O+ < S+ < Se+ (λmax for 3 (Raz = R3 = H; R2 = Ph), 21 (Raz = H and 22 (Raz = H) are 530, 572 and 600) could be associated with the decrease in the electronegativity of heteroatom (O, 3.5; S, 2.5; Se, 2.4) [49]. The 1H-NMR spectra of chalco-geno-pyrylium salts show the same characteristics and trends as in the case presented above for pyranylium salts.

4. Other Systems Stabilized by Azulen-1-yl Moieties In this last section reference will be made to some special cases of azulen-1-yl moiety participation in the stability of some carbocations and even of some neutral molecules. In connection with the stabilization of triarylmethylium ions by at least one azulen- Symmetry 2021, 13, 526 1-yl moiety discussed before, the delocalized mono-carbenium ions, salt 23, stabilized15 of by 21 largely conjugate π electrons including azulen-1-yl moieties, is presented. Salt 23 was obtained by condensation of all-trans-retinal with azulenes (Scheme 18) [50].

Symmetry 2021, 13, x FOR PEER REVIEW 17 of 23

Scheme 18. Condensation of all-trans-retinal with azulenes. ConsideringConsidering the good electron the good donor electron property donor of both property ferrocene of both and ferrocene of azulen-1-yls, and of azulen-1-yls, Farrell et al.Farrell [51] used et al. ferrocene-azulenium [52] used ferrocene-azulenium carbocations carbocations and their andvinyl-ogs their vinyl-ogs as tetra- as tetraﬂuo-

fluoroboratesroborates to investigate to investigate a novel aseries novel of series monometallic of monometallic monocations, monocations, 24n. Starting24n. Starting from from formylformyl ferrocene ferrocene and azulenes and azulenes as precursors, as precursors, the yields the yields of products of products 24n24 weren were be- between 58% tween 58% andand 68% 68% (Scheme (Scheme 19). 19).

Scheme 19. Ferrocene-azulenium carbocations. Scheme 19. Ferrocene-azulenium carbocations. Contrary to the very low stability of most carbocations with hydrocarbon skeleton, Contrarysome to the cyclic very cations low stability such as of cyclo-propenyl most carbocations [53] have with remarkable hydrocarbon stability. skeleton, In fact, this sys- some cyclic cationstem is thesuch simplest as cyclo-propenyl aromatic Hückel [52] have system. remarkable The substitutionstability. In fact, of this this cation sys- with three tem is the simplestcyclopropyl aromatic [54] Hückel or three system. guaiazulene The substitution moieties [55of ]this dramatically cation with increases three cy- the value of clopropyl [53]pK orR+ threecompared guaiazulene with the moieties compound [54] withdramatically a three phenyl increases ring the as value can be of seen pKR+ in Scheme 20. compared withFrom the the compound data in Schemewith a three 20 we phenyl can see ring the as high can be difference seen in Scheme between 20. the From pK R+ for triph- the data in Schemeenylmethylium 20 we can and see the the tri(azulen-1-yl)methylium high difference between cationthe pK asR+ comparedfor triphenylme- with the difference thylium andbetween the tri(azulen-1-y cyclo-propenyliuml)methylium cations cation25 as(R compared = Ph) and with25 (R the = guaiazulene-3-yl difference be- ). The com- tween cyclo-propenyliumpound 25 (R = guaiazulene-3-ycations 25 (R =) Ph) was and obtained 25 (R in = the guaiazulene-3-yl). Friedel Crafts reaction The com- of C3C13 + AlC14 pound 25 (R = guaiazulene-3-y) was obtained in the Friedel Crafts reaction of C3C13 + AlC14 (prepared from tetra-chloro-cyclo-propene and AlC13) with three molar equivalents of guaiazulene in dichloromethane at −70 °C [54].

Scheme 20. pKR+ values for some carbocations with hydrocarbon skeleton.

Regarding the azulen-1-yl system contribution to the charge distribution in neutral molecules, without detailing this extensive subject that goes beyond this review, an in- formative example will be presented below. The azulenyl squarines that will be discussed briefly, already synthesized in 1966 [55], have interested a number of researchers due to the optical properties of the compounds as well as for some biological applications. It should be mentioned that in the over 50 years since the birth of the first azulenyl squarines a huge number of compounds have been reported, some of them being covered by patents and in 2017 a consistent review was published on this topic [56]. The general procedure for obtaining these compounds, 26, is shown in Scheme 21 [57]. The presence of electron-donating groups in an aromatic system employed in a squarine synthesis tends to favor the reaction, and indeed the yield of reactions between azulene and squaric acid proceeds satisfactorily.

Symmetry 2021, 13, x FOR PEER REVIEW 17 of 23

Considering the good electron donor property of both ferrocene and of azulen-1-yls, Farrell et al. [51] used ferrocene-azulenium carbocations and their vinyl-ogs as tetra- fluoroborates to investigate a novel series of monometallic monocations, 24n. Starting from formyl ferrocene and azulenes as precursors, the yields of products 24n were between 58% and 68% (Scheme 19).

Scheme 19. Ferrocene-azulenium carbocations.

Contrary to the very low stability of most carbocations with hydrocarbon skeleton, some cyclic cations such as cyclo-propenyl [52] have remarkable stability. In fact, this sys- Symmetry 2021, 13, 526 16 of 21 tem is the simplest aromatic Hückel system. The substitution of this cation with three cyclopropyl [53] or three guaiazulene moieties [54] dramatically increases the value of pKR+ compared with the compound with a three phenyl ring as can be seen in Scheme 20. From the data in Scheme 20 we can see the high difference between the pKR+ for triphenylme- (prepared from tetra-chloro-cyclo-propene and AlC13) with three molar equivalents of gua- thylium and the tri(azulen-1-yl)methylium cation as compared with the difference be- iazulene in dichloromethane at −70 ◦C[54]. tween cyclo-propenylium cations 25 (R = Ph) and 25 (R = guaiazulene-3-yl). The com- Regarding the azulen-1-yl system contribution to the charge distribution in neutral pound 25 (R = guaiazulene-3-y) was obtained in the Friedel Crafts reaction of C3C13 + AlC14 molecules, without detailing this extensive subject that goes beyond this review, an infor- (prepared from tetra-chloro-cyclo-propene and AlC13) with three molar equivalents of mative exampleguaiazulene will be presented in dichloromethane below. at −70 °C [54].

Scheme 20. pKR+ values for some carbocations with hydrocarbon skeleton. Scheme 20. pKR+ values for some carbocations with hydrocarbon skeleton. The azulenyl squarines that will be discussed brieﬂy, already synthesized in 1966 [56], have interested a numberRegarding of researchers the azulen-1-yl due tosystem the optical contribution properties to the of charge the compounds distributionas in neutral well as for somemolecules, biological without applications. detailing It shouldthis extensive be mentioned subject that that goes in thebeyond over this 50 yearsreview, an in- since the birth offormative the ﬁrst example azulenyl will squarines be presented a huge below. number of compounds have been reported, some of themThe azulenyl being covered squarines by that patents will be and discussed in 2017 briefly, a consistent already review synthesized was in 1966 [55], have interested a number of researchers due to the optical properties of the com- published on this topic [57]. The general procedure for obtaining these compounds, 26, pounds as well as for some biological applications. It should be mentioned that in the over is shown in Scheme 21[ 58]. The presence of electron-donating groups in an aromatic Symmetry 2021, 13, x FOR PEER REVIEW 50 years since the birth of the first azulenyl squarines a huge number of compounds18 of 23 have system employedbeen in areported, squarine some synthesis of them tends being to covered favor the byreaction, patents and and in indeed 2017 a theconsistent yield review of reactions betweenwas published azulene andon this squaric topic acid[56]. proceedsThe general satisfactorily. procedure for obtaining these compounds, 26, is shown in Scheme 21 [57]. The presence of electron-donating groups in an aromatic system employed in a squarine synthesis tends to favor the reaction, and indeed the yield of reactions between azulene and squaric acid proceeds satisfactorily.

Scheme 21. Azulen-1-yl squarines.

Without goinggoing into into detail, detail, some some information information on the on structure the structure of the azulenyl of the squarinesazulenyl squarinesis required. is Therequired. X-ray The crystal X-ray structure crystal structure of compound of compound26 (Raz = 26 H (R oraz 3,8-Me2, = H or 3,8-Me2, 5-iPr) [57 5-] ishowsPr) [56] the shows shorter the C1-C2shorter bond C1-C2 as bond compared as compared with the with other the five other ring five bonds. ring bonds. At the At same the sametime, time, the bond the bond length length for sixfor bondssix bonds in thein th bige big ring ring are are reduced reduced as as compared compared withwith the distance between the atoms in the five five membered ring and the longer azulene bond is between C3a and C8a. (Scheme 21). These observations seem seem to suggest a more efficientefficient π–electron conjugation over C3a-C4-C5-C6-C7-C8-C8aC3a-C4-C5-C6-C7-C8-C8a thanthan aa tropyliumtropylium structure.structure. The presence ofof [[18]18] nulenenulene substructuressubstructures with with 26 26ππelectrons electrons within within the the macrocycle macrocycle is isresponsible responsible for for the the aromatic aromatic characteristics characteristics of porphyrins. of porphyrins. According According to this to model,this model, a large a largenumber number of other of other compounds, compounds, including including some some containing containing azulene azulene systems systems in the in molecule, the molecule,have been have made been overmade time. over Lashtime. etLash al. hadet al. the had idea the of idea replacing of replacing one or one more or more pyrrole pyrrole rings rings in the porphyrin macrocycle with the five rings of azulene, so edifying a new class of compounds, azuli-porphyrins and related carba-porphyrinoid compounds. One of the syntheses of azuliporphyrins is based on the application of the “3+1”variant of the MacDonald reaction as can be seen in Scheme 22. Azulene-1,3-dialdehyde was condensed with tri-pyrene in the presence of HBF4 in dichloromethane followed by oxidation with DDQ. The compound 27’s porphyrin analogues, due to the participation of the five azulene ring at the stabilization of product, were generated in good yields. A large number of azuli-porphyrins were also obtained by Lash’s research team from which only two more examples, 28 and 29, were selected. In the last compound two azulene moieties were inserted into the molecular structure.

Symmetry 2021, 13, 526 17 of 21

in the porphyrin macrocycle with the ﬁve rings of azulene, so edifying a new class of compounds, azuli-porphyrins and related carba-porphyrinoid compounds. One of the syntheses of azuliporphyrins is based on the application of the “3+1” variant of the MacDonald reaction as can be seen in Scheme 22. Azulene-1,3-dialdehyde was condensed with tri-pyrene in the presence of HBF4 in dichloromethane followed by oxidation with DDQ. The compound 27’s porphyrin analogues, due to the participation of the ﬁve azulene ring at the stabilization of product, were generated in good yields. A large number of azuli-porphyrins were also obtained by Lash’s research team from which only Symmetry 2021, 13, x FOR PEER REVIEW 28 29, 19 of 23 two more examples, and were selected. In the last compound two azulene moieties were inserted into the molecular structure.

SchemeScheme 22. 22. SynthesisSynthesis of azuli-porphyrins. of azuli-porphyrins.

Finally, and and as as a curiosity, a curiosity, the theattempts attempts to realize to realize a system a systemanalog to analog that of toporphy- that of porphyrin, inrin, which in which the the four four ﬁve-memberedfive-membered rings rings belo belongng to azulenes to azulenes will be presented. will be presented. Starting Starting fromfrom the theoretically theoretically exciting, exciting, if presumed, if presumed, quatyrin quatyrin system (Scheme system 23), (Scheme an analog 23 ),to an analog to thatthat of porphyrin, porphyrin, the the reparation reparation of calix of [4] calix azulenes, [4] azulenes, 30, began30 by, beganreacting by azulenes reacting with azulenes with paraformaldehyde in the presence of florisil. However, the realized molecules did not have the desired structure, namely [18] annulene substructures with 26π electrons. Using the tetra-aryl compound 31, after oxidation with DDQ and an addition of HBF4·Et2O, the tetra-cation 32 was generated. Surprisingly, the chemical shifts in 1H-NMR spectrum of 32

Symmetry 2021, 13, 526 18 of 21

Symmetry 2021, 13, x FOR PEER REVIEWparaformaldehyde in the presence of ﬂorisil. However, the realized molecules did20 notof 23 have the desired structure, namely [18] annulene substructures with 26π electrons. Using the tetra-aryl compound 31, after oxidation with DDQ and an addition of HBF4·Et2O, the tetra-cation 32 was generated. Surprisingly, the chemical shifts in 1H-NMR spectrum of 32areare consistent consistent with with a non-aromatic a non-aromatic structure. structure. This This finding, ﬁnding, as aswell well as asthe the lack lack of ofcoplanar- copla- narityity of ofthe the macrocycle, macrocycle, determined determined by by X-ray X-ray spectra, spectra, seems toto indicateindicate thethe predominant predominant 2 participationparticipation of of the the structure structure32B 32Bwith with the the charges charges located located at at the the four four Csp Csp2+,+, compared compared to to thethe structure structure32A 32Awith with the the tropylium tropylium ions. ions. Thus, Thus, the the macrocyclic macrocyclic aromatic aromatic ring ring current current is is essentiallyessentially absent. absent.

+ +

Scheme 23. Macrocycles including azulene moieties. Scheme 23. Macrocycles including azulene moieties. 5. Conclusions 5. ConclusionsAzulenes, those exceptional compounds related to natural derivatives, have a special structureAzulenes, that gives those them exceptional properties compounds totally different related fromto natural those derivatives, of alternating have aromatic a special hydrocarbonsstructure that andgives even them from properties the non-alternating totally different ones from with whichthose of they alternating are related. aromatic This paperhydrocarbons proposes and a brief even look from at the one non-alternatin of the propertiesg ones of with azulenes. which The they configuration are related. This of thepaperπ-electron proposes system a brief over look the at sevenone of andthe prop five azuleneerties of ringsazulenes. develops The configuration a dipole moment of the thatπ-electron favors asystem displacement over the of seven the electronsand five az towardsulene rings an acceptor develops substituted a dipole moment in position that 1favors of the a azulene. displacement In this of way the theelectrons seven-ring towards adopts an acceptor the stable substituted structure in of position the tropylium 1 of the ionazulene. and consequently In this way the stabilizes seven-ring the entireadopts system the stable in which structure it is involved.of the tropylium This explains ion and theconsequently ease of azulenes stabilizes in reactingthe entire with system electrophilic in which it substitutions is involved. This as well explains as in the donating ease of electronsazulenes to in acceptor reacting systems. with electrophilic This paper substi is focusedtutions on as the well donor as propertyin donating of azulene electrons and to isacceptor limited systems. to the most This relevant paper is acceptors, focused on namely the donor methylium property ions of andazulene positive and is charged limited heteroaryls.to the most Severalrelevant cases acceptors, of neutral namely molecules methylium benefiting ions and from positive azulen-1-yl charged assistance heteroaryls. are alsoSeveral briefly cases described. of neutral It wasmolecules considered benefiting useful from to briefly azulen-1-yl summarize assistance the synthesis are also ofbriefly the compoundsdescribed. It considered. was considered The useful change to in brie thefly charge summarize distribution the synthesis of the of studied the compounds systems resultsconsidered. in variations The change in the in chemical the charge shifts distribu of protonstion of and the carbon studied atoms systems in the results NMR spectra,in varia- astions well in as the in chemical some changes shiftsin of theprotons UV-Vis and spectra. carbon The atoms pK inR+ thevalue NMR of somespectra, pseudo-bases, as well as in some changes in the UV-Vis spectra. The pKR+ value of some pseudo-bases, such as cations, is a valuable indicator of their stability. The analysis of the mentioned parameters highlights the role of azulene as an electron donor in the stability of the systems in which it is included, especially in those with positive charge. Certainly, this property of azulene

Symmetry 2021, 13, 526 19 of 21

such as cations, is a valuable indicator of their stability. The analysis of the mentioned parameters highlights the role of azulene as an electron donor in the stability of the systems in which it is included, especially in those with positive charge. Certainly, this property of azulene will further stimulate the building of chemical systems belonging to a series of areas of theoretical interest but also in those of technical interest, such as dyes and active materials for electronic, optoelectronic and electrochromic devices.

Funding: This research received no external funding. Institutional Review Board Statement: Not applicable. Informed Consent Statement: Not applicable. Data Availability Statement: Data available in a publicly accessible repository. Acknowledgments: The author is grateful to the late Klaus Hafner from the Institute of Organic Chemistry, Technische Universität Darmstadt for helpful discussions. These discussions were very useful and will be long time remembered. Conflicts of Interest: The author declare no conflict of interest, financial or otherwise.

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