tropolone

Many methods have been described for the synthesis of tropolone.{{cite journal |first=Richard A. |last=Minns |title=Tropolone |journal=Org. Synth. |year=1977 |volume=57 |page=117 |doi=10.15227/orgsyn.057.0117}} One involves bromination of 1,2-cycloheptanedione with N-bromosuccinimide followed by dehydrohalogenation at elevated temperatures, while another uses acyloin condensation of the ethyl ester of pimelic acid the acyloin again followed by oxidation by bromine.{{cite journal |title=Tropones and Tropolones |first=Peter L. |last=Pauson |journal=Chem. Rev. |date=1955 |volume=55 |issue=1 |pages=9–136 |doi=10.1021/cr50001a002}}

:File:TropoloneGenSynth.png

An alternate route is a [2+2] cycloaddition of cyclopentadiene with a ketene to give a bicyclo[3.2.0]heptyl structure, followed by hydrolysis and breakage of the fusion bond to give the single ring:

:File:OS tropolone from CpH.svg

Thy hydroxyl group of tropolone is acidic, having a pK_a of 7, which is in between that of phenol (10) and benzoic acid (4). The increased acidity compared to phenol is due to resonance stabilization with the carbonyl group, as a vinylogous carboxylic acid.

The compound readily undergoes O-alkylation to give cycloheptatrienyl derivatives, which in turn are versatile synthetic intermediates. With metal cations, it undergoes deprotonation to form a bidentate ligand, such as in the {{chem2|Cu(O2C7H5)2}} complex.

The carbonyl group is also highly polarized, as common for tropones. There can be substantial hydrogen bonding between it and the hydroxyl group, leading to rapid tautomerization: the structure is symmetric on the NMR timescale.{{cite thesis |title=Detoxification of thujaplicins in living western red cedar (Thuja plicata Donn.) trees by microorganisms |first=Lehong |last=Jin |type=PhD |publisher=University of British Columbia |date=February 1987}}

:File:TropoloneTaut.svg

Around 200 naturally occurring tropolone derivatives have been isolated, mostly from plants and fungi.{{cite journal |doi=10.1039/b711474e |title=A fresh look at natural tropolonoids |date=2008 |last1=Bentley |first1=Ronald |journal=Nat. Prod. Rep. |volume=25 |issue=1 |pages=118–138 |pmid=18250899 }}{{cite journal |doi=10.1039/c8np00078f |title=Tropolone natural products |date=2019 |last1=Guo |first1=Huijuan |last2=Roman |first2=David |last3=Beemelmanns |first3=Christine |journal=Natural Product Reports |volume=36 |issue=8 |pages=1137–1155 |pmid=30556819 }}{{cite journal |last1=Zhao |first1=Jian Zhao and Jian |title=Plant Troponoids: Chemistry, Biological Activity, and Biosynthesis |journal=Current Medicinal Chemistry |date=30 September 2007 |volume=14 |issue=24 |pages=2597–2621 |doi=10.2174/092986707782023253 |pmid=17979713}}{{cite journal |doi=10.1039/b711474e |title=A fresh look at natural tropolonoids |date=2008 |journal=Nat. Prod. Rep. |volume=25 |issue=1 |pages=118–138 |pmid=18250899 | vauthors = Bentley R }} Tropolone compounds and their derivatives include {{chem name|dolabrins, dolabrinols, thujaplicins, thujaplicinols, stipitatic acid, stipitatonic acid, nootkatin, nootkatinol, puberulic acid, puberulonic acid, sepedonin, 4-acetyltropolone, pygmaein, isopygmaein, procein, chanootin, benzotropolones}} (such as {{chem name|purpurogallin, crocipodin, goupiolone A and B), theaflavin}} and derivatives {{chem name|bromotropolones, tropoisoquinolines and tropoloisoquinolines (such as grandirubrine, imerubrine, isoimerubrine, pareitropone, pareirubrine A and B), colchicine, colchicone}} and others.{{cite journal |last1=Liu |first1=Na |last2=Song |first2=Wangze |last3=Schienebeck |first3=Casi M. |last4=Zhang |first4=Min |last5=Tang |first5=Weiping |title=Synthesis of naturally occurring tropones and tropolones |journal=Tetrahedron |date=December 2014 |volume=70 |issue=49 |pages=9281–9305 |doi=10.1016/j.tet.2014.07.065 |pmid=25400298 |pmc=4228802}} Tropolone arises via a polyketide pathway, which affords a phenolic intermediate that undergoes ring expansion.{{cite journal |last1=Pietra |first1=F. |title=Seven-membered conjugated carbo- and heterocyclic compounds and their homoconjugated analogs and metal complexes. Synthesis, biosynthesis, structure, and reactivity |journal=Chemical Reviews |year=1973 |volume=73 |issue=4 |pages=293–364 |doi=10.1021/cr60284a002}}

They are especially found in specific plant species, such as Cupressaceae and Liliaceae families. Tropolones are mostly abundant in the heartwood, leaves and bark of plants, thereby the essential oils are rich in various types of tropolones. The first natural tropolone derivatives were studied and purified in the mid-1930s and early-1940s.{{cite journal |last1=Nakanishi |first1=Koji |title=Tetsuo Nozoe's "Autograph Books by Chemists 1953-1994": An Essay: Tetsuo Nozoe's "Autograph Books by Chemists 1953-1994": An Essay |journal=The Chemical Record |date=June 2013 |volume=13 |issue=3 |pages=343–352 |doi=10.1002/tcr.201300007 |pmid=23737463 |doi-access=free}} Thuja plicata, Thujopsis dolabrata, Chamaecyparis obtusa, Chamaecyparis taiwanensis and Juniperus thurifera were in the list of trees from which the first tropolones were identified. The first synthetic tropolones were thujaplicins derived by Ralph Raphael.{{cite journal |last1=Cook |first1=J. W. |last2=Raphael |first2=R. A. |last3=Scott |first3=A. I. |title=149. Tropolones. Part II. The synthesis of α-, β-, and γ-thujaplicins |journal=J. Chem. Soc. |date=1951 |pages=695–698 |doi=10.1039/JR9510000695}}

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