Quantum-Chemical Search for Keto Tautomers of Azulenols in Vacuo and Aqueous Solution

Ewa D Raczyńska

doi:10.3390/sym13030497

Abstract

Keto-enol prototropic conversions for carbonyl compounds and phenols have been extensively studied, and many interesting review articles and even books appeared in the last 50 years. Quite a different situation takes place for derivatives of biologically active azulene, for which only scanty information on this phenomenon can be found in the literature. In this work, quantum-chemical studies have been undertaken for symmetrically and unsymmetrically substituted azulenols (constitutional isomers of naphthols). Stabilities of two enol (OH) rotamers and all possible keto (CH) tautomers have been analyzed in the gas phase {DFT(B3LYP)/6-311+G(d,p)} and also in aqueous solution {PCM(water)//DFT(B3LYP)/6-311+G(d,p)}. Contrary to naphthols, for which the keto forms can be neglected, at least one keto isomer (C1H, C2H, and/or C3H) contributes significantly to the tautomeric mixture of each azulenol to a higher degree in vacuo (non-polar environment) than in water (polar amphoteric solvent). The highest amounts of the CH forms have been found for 2- and 5-hydroxyazulenes, and the smallest ones for 1- and 6-hydroxy derivatives. The keto tautomer(s), together with the enol rotamers, can also participate in deprotonation reaction leading to a common anion and influence its acid-base properties. The strongest acidity in vacuo exhibits 6-hydroxyazulene, and the weakest one displays 1-hydroxyazulene, but all azulenols are stronger acids than phenol and naphthols. Bond length alternation in all DFT-optimized structures has been measured using the harmonic oscillator model of electron delocalization (HOMED) index. Generally, the HOMED values decrease for the keto tautomers, particularly for the ring containing the labile proton. Even for the keto tautomers possessing energetic parameters close to those of the enol isomers, the HOMED indices are low. However, some kind of parallelism exists for the keto forms between their relative energies and HOMEDs estimated for the entire molecules.

Highlights

Owing to remarkable physicochemical properties and biological activities, azulene and its derivatives have attracted the particular attention of many theoretical and experimental researchers for more than two hundred years [1,2,3,4]
Note that the C9C10 bond is even shorter for these anions (1.463 and 1.452 Å, respectively) than that for the parent azulene, indicating an increase of electron delocalization and aromaticity fboornthdes)f,ivaree-mcleomsebteoreHdOriMngEDin1A1s−3ananddvAar−y5.fFroomr A0−.48,1btooth0.8th9e
On the basis of our quantum-chemical calculations carried out for hydroxyazulenes in vacuo and aqueous solution, we can conclude that the choice of computational-chemistry methods is a suitable way for testing the keto forms in polycyclic and well delocalized hydroxy arenes

Summary

Introduction

Owing to remarkable physicochemical properties and biological activities, azulene and its derivatives have attracted the particular attention of many theoretical and experimental researchers for more than two hundred years [1,2,3,4]. Azulene-hydrocarbons (sesquiterpenes) and their derivatives can be employed as dye materials Their color depends on the nature and position of the substituent(s) introduced at carbon atom(s) [10,11]. Due to remarkable polarizability of the azulene system, its derivatives show promising applications in the design of new organic superbases [19] They can be used as advanced organic materials (organic metals, liquid crystals, polymers, nonlinear optical chromophores, solar cells, etc.) [2,3,4,20,21,22,23,24]. They can be used as advanced organic materials (organic metals, liquid crystals, fdCmdpeaHanMsnopi[basnblhgmwrppzecammsnsoaa2oxtznrauoieelraaihaurtüaceezftcha5urogareamraugdplrsplrcugofoeeuobdliomoubt]cyipeermhe-ueallidhnon.hmmmrscetpkieeldeczrsdlmhrdneScπtoeaStbstiemtltIeoantpoeeehaSurrtuhtstyiihaenbsusraninea-pleylcvnhcmduupellmia,cnrsiarenaeaerbposemy[rgzaeatatckhrseatslmel2rirlt,smc[isπrhricsieeererletasonesesczeel2id,l5sevibteounl,talscdneb-anazxlouladd5tao.ni]aoensaeietabatarraorrcunlen.hnetl]ttbolsrhlTofsrleuπaurrcueuap.leercrcseoItlaicenuienilrhut[ycpIieey[lbornnocey-ticlthtcepldno2sen2pseautihonltyecletcisrect.taa[iaai9husise7stahlrtrtotlilhalaaenlt,2atesTnlluluctauo,ailcro,oztisrfye(asd3ls26tasrzecfthutnuttdcFhredhsbrumnnhosoosir,0v8]rtrluauahaoswaovc(isegesie.reorsolie]en]argvoosllnlc-teeleiotney.nepr.eBvpenitlpceublgliegaturr(adnnoytic-nxe-taentsaaFranIe-gbvtxhuhnhd[rmelphr.paeenhrtpase2tel)flceaioheaiaericitestiigoit,se,ugtatitc6unaol,pbsoelo[(rntefriiboarnifilte1lewca2sFu]ifubcimmglcmogcaon.yiheilvi.ieat)eacl–veaiceirtdisvratell.psshTangBdeertssab4wnbeelh-etfeestTtoneiadnsoirechmuuhueei,rhecdac-pe-ast-2monn,h1ooaireom,miipcteoershbrms,eoetnoitfs0eer)ttldlfneaeeehnoifhghfwrsrxoeyiwo.moldac–tfeelswduedeio-.oretgeaacahaem1cinmTstp2rpbemirymhtsnhtmtesleCotrgt)cih4meyochthhsroenuri.beegerereeoloibohno]ynbe,otiab[eoeilovrannTirert.ioolnhaglne2frpitctennetrnsialaeroppiettghefmnh.orrig6lecarelaihdscasdpsrneqdohheeaothtpeeCit]naaspseiilsasisilhtehu.dshaprsitocdsfde,lpnpehq,psuofhnhpsineeeipeiiysihlreaficBanhuoytrcnsnbdeichstdatoeestrcnhsytzotitzgrohyoeyglytsxes.srlnsrohihlioaeiuthtuwaneccdigatecoamnccsecc,cnCaihmcinafioanslaiol,qnrrloaelhlnusputtmdgeoeseatooedoiyuaelmnlueopcpuhplptmhtcnvesnyilcnppoptzrnsh,ysaoolteaetethoo,hnnhheie,ppeatirueeoaseespenln-mlf[nhuoawrtaleufeaeresc,o2ethznncllmheeh,eotlnshonao,meonsaicocq7aueaulscyttesc,gteartyranw,etdlfaatdi,]nfneiszusahovlnseiliac,iwss.enedetdla,oseutnictpenoaeeadetstthlixbpcciynMowznaihnsirswtnodllsrlcvlopsoooce,aeesoeereeu,pt,mloeeaiatleefhnrmhncnepowocnnslensnlycleh,pmnncurpbathhyaiteteieierrtaoeexuwmgo,nltalrpxrdhrccaeictnoe,ioezeweb,ipnoosceisicgna.-pttcooismsofpetzssefur)oemupeollarpslphoiothouaveeraatseca[almizi[nwsroiherew[nserso2ttsebetin2crcitau2ssahlrnd,txrthpotinntts–trromp9aiieadlyiliou7tithliza,tpluaeoiamlocn4ixess,owlnreierhih]f,yc3uciandenbutnmtls,cil-nf.osfnttip2aty0aezwlcimsoeletasalwoluenefsnesb,M0ahirub]aeanrrea[rirtpiunuf[n.shn1xlrioai–heneysbnieaoorra1titpsdhsaseoeba,-z2nimepwhnadyivsattp,2o[emltlddarltih2hrusb4a2lteateele[h5idfdhhmiilreobty52et]beef9nvtlraansyep–eibtiyt.aooeewa–er7tnt,eeirfneeghmwfur23yoilun,eircafvzf2rHf,unloerigevds28oaeeu0nmulexeaonuee8tisbstastnizap8]lanrüi]tdcazposrptlh]glee.oer.eheesb]eahstpt.oeo,teunrc[tlndet.srirnnnxF1raebiankdailonvodlnmeFnonsieIchaetr,on,peiHaedvweesltnled2eponuaagrwaniysrdn1nnoohlaee[esv5flbplürehimsir2y0ermx,ufimzadargt–seeiiidddhnncia7cbheittcznesCa2mnxwelddbvkhahsaegto,aloix1eeeenas8d2xaysbfh-ieenarrerslmpna0tahb-hbffm]ee8mshekplryatolpfde.mtgztoedeite2oivi][ecidloeomrlagfmhvheo.2bpbervrFeicunirateorenfmpenvlmhteea7ahnfealIn1ilfooeanraollonoyulttteaedlsnsn]aylek02eengeoCrrrssssf-e---t-.,,,eess0rrt---,. PAs and GBs have been calculated for the major and minor isomers of tautomeric systems as well as for their mixtures

Deprotonated Forms of Hydroxyazulenes

Bonds Lengths Alternation in Neutral and Anionic Forms of Hydroxyazulenes

Favored Isomers for Hydroxyazulenes in Vacuo and Aqueous Solution

Conclusions