Tropolone is an

organic compound In chemistry, organic compounds are generally any chemical compounds that contain carbon-hydrogen or carbon-carbon bonds. Due to carbon's ability to catenate (form chains with other carbon atoms), millions of organic compounds are known. The ...

with the chemical formula . It is a pale yellow solid that is soluble in organic solvents. The compound has been of interest to research chemists because of its unusual electronic structure and its role as a ligand precursor. Although not usually prepared from

tropone Tropone or 2,4,6-cycloheptatrien-1-one is an organic compound with some importance in organic chemistry as a non-benzenoid aromatic. The compound consists of a ring of seven carbon atoms with three conjugated alkene groups and a ketone group. Th ...

, it can be viewed as its derivative with a

hydroxyl group In chemistry, a hydroxy or hydroxyl group is a functional group with the chemical formula and composed of one oxygen atom covalently bonded to one hydrogen atom. In organic chemistry, alcohols and carboxylic acids contain one or more hydroxy g ...

in the 2-position.

Synthesis and reactions

Many methods have been described for the synthesis of tropolone. One involves bromination of 1,2-cycloheptanedione with ''N''-bromosuccinimide followed by

dehydrohalogenation In chemistry, dehydrohalogenation is an elimination reaction which removes a hydrogen halide from a substrate. The reaction is usually associated with the synthesis of alkenes, but it has wider applications. Dehydrohalogenation from alkyl halid ...

at elevated temperatures, while another uses

acyloin condensation Acyloin condensation is a reductive coupling of two carboxylic esters using metallic sodium to yield an α-hydroxyketone, also known as an acyloin. The reaction is most successful when ''R'' is aliphatic and saturated. The reaction is performe ...

of the ethyl

ester In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides ar ...

pimelic acid Pimelic acid is the organic compound with the formula HO2C(CH2)5CO2H. Pimelic acid is one unit longer than a related dicarboxylic acid, adipic acid, a precursor to many polyesters and polyamides. However compared to adipic acid, pimelic acid is ...

the

acyloin Acyloins or α-hydroxy ketones are a class of organic compounds which all possess a hydroxy group adjacent to a ketone group. The name acyloin is derived from the fact that they are formally derived from reductive coupling of carboxylic acyl gro ...

again followed by oxidation by

bromine Bromine is a chemical element with the symbol Br and atomic number 35. It is the third-lightest element in group 17 of the periodic table (halogens) and is a volatile red-brown liquid at room temperature that evaporates readily to form a simila ...

. :

An alternate route is a +2

cycloaddition In organic chemistry, a cycloaddition is a chemical reaction in which "two or more Unsaturated hydrocarbon, unsaturated molecules (or parts of the same molecule) combine with the formation of a cyclic adduct in which there is a net reduction of th ...

cyclopentadiene Cyclopentadiene is an organic compound with the chemical formula, formula C5H6.LeRoy H. Scharpen and Victor W. Laurie (1965): "Structure of cyclopentadiene". ''The Journal of Chemical Physics'', volume 43, issue 8, pages 2765-2766. It is often ab ...

with a

ketene In organic chemistry, a ketene is an organic compound of the form , where R and R' are two arbitrary monovalent chemical groups (or two separate substitution sites in the same molecule). The name may also refer to the specific compound etheno ...

to give a bicyclo .2.0eptyl structure, followed by

hydrolysis Hydrolysis (; ) is any chemical reaction in which a molecule of water breaks one or more chemical bonds. The term is used broadly for substitution reaction, substitution, elimination reaction, elimination, and solvation reactions in which water ...

and breakage of the fusion bond to give the single ring: : OS tropolone from CpH

Thy hydroxyl group of tropolone is

acidic In computer science, ACID ( atomicity, consistency, isolation, durability) is a set of properties of database transactions intended to guarantee data validity despite errors, power failures, and other mishaps. In the context of databases, a sequ ...

, having a p''K''_a of 7, which is in between that of

phenol Phenol (also called carbolic acid) is an aromatic organic compound with the molecular formula . It is a white crystalline solid that is volatile. The molecule consists of a phenyl group () bonded to a hydroxy group (). Mildly acidic, it req ...

(10) and

benzoic acid Benzoic acid is a white (or colorless) solid organic compound with the formula , whose structure consists of a benzene ring () with a carboxyl () substituent. It is the simplest aromatic carboxylic acid. The name is derived from gum benzoin, wh ...

(4). The increased acidity compared to phenol is due to

resonance stabilization In chemistry, resonance, also called mesomerism, is a way of describing bonding in certain molecules or polyatomic ions by the combination of several contributing structures (or ''forms'', also variously known as ''resonance structures'' or '' ...

with the carbonyl group, as a

vinylogous In organic chemistry, vinylogy is the transmission of electronic effects through a conjugated organic bonding system. The concept was introduced in 1926 by Ludwig Claisen to explain the acidic properties of formylacetone and related ketoaldehyde ...

carboxylic acid. The compound readily undergoes ''O''-

alkylation Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting ...

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 complex. The carbonyl group is also highly polarized, as common for

s. There can be substantial

hydrogen bonding In chemistry, a hydrogen bond (or H-bond) is a primarily electrostatic force of attraction between a hydrogen (H) atom which is covalently bound to a more electronegative "donor" atom or group (Dn), and another electronegative atom bearing a l ...

between it and the hydroxyl group, leading to rapid

tautomerization Tautomers () are structural isomers (constitutional isomers) of chemical compounds that readily interconvert. The chemical reaction interconverting the two is called tautomerization. This conversion commonly results from the relocation of a hydr ...

: the structure is symmetric on the NMR timescale. : TropoloneTaut

Natural occurrence

Around 200 naturally occurring tropolone derivatives have been isolated, mostly from

plants Plants are predominantly Photosynthesis, photosynthetic eukaryotes of the Kingdom (biology), kingdom Plantae. Historically, the plant kingdom encompassed all living things that were not animals, and included algae and fungi; however, all curr ...

and

fungi A fungus ( : fungi or funguses) is any member of the group of eukaryotic organisms that includes microorganisms such as yeasts and molds, as well as the more familiar mushrooms. These organisms are classified as a kingdom, separately from ...

. Tropolone compounds and their derivatives include (such as and derivatives and others. Tropolone arises via a

polyketide Polyketides are a class of natural products derived from a precursor molecule consisting of a chain of alternating ketone (or reduced forms of a ketone) and methylene groups: (-CO-CH2-). First studied in the early 20th century, discovery, biosynth ...

pathway, which affords a

ic intermediate that undergoes ring expansion. They are especially found in specific plant species, such as ''

Cupressaceae Cupressaceae is a conifer family, the cypress family, with worldwide distribution. The family includes 27–30 genera (17 monotypic), which include the junipers and redwoods, with about 130–140 species in total. They are monoecious, subdio ...

'' and ''

Liliaceae The lily family, Liliaceae, consists of about 15 genera and 610 species of flowering plants within the order Liliales. They are monocotyledonous, perennial, herbaceous, often bulbous geophytes. Plants in this family have evolved with a fair ...

'' 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. ''

Thuja plicata ''Thuja plicata'' is an evergreen coniferous tree in the cypress family Cupressaceae, native to western North America. Its common name is western redcedar (western red cedar in the UK), and it is also called Pacific redcedar, giant arborvitae, w ...

'', ''

Thujopsis dolabrata ''Thujopsis'' () is a genus of conifers in the cypress family ( Cupressaceae), the sole member of which is ''Thujopsis dolabrata''. It is endemic to Japan, where it is named ''asunaro'' (). It is similar to the closely related genus ''Thuja'' ...

'', ''

Chamaecyparis obtusa ''Chamaecyparis obtusa'' (Japanese cypress, hinoki cypress or hinoki; ja, 檜 or , ) is a species of cypress native to central Japan in East Asia, and widely cultivated in the temperate northern hemisphere for its high-quality timber and orna ...

'', ''

Chamaecyparis taiwanensis ''Chamaecyparis taiwanensis'' (Taiwan cypress; ) is a species of cypress, native to the mountains of Taiwan, where it grows at altitudes of 1300–2800 m.Rushforth, K. (1987). ''Conifers''. Helm . Description It is a slow-growing coniferous tr ...

'' and ''

Juniperus thurifera ''Juniperus thurifera'' (Spanish juniper) is a species of juniper native to the mountains of the western Mediterranean region, from southern France (including Corsica) across eastern and central Spain to Morocco and locally in northern Algeria. ...

'' were in the list of trees from which the first tropolones were identified. The first synthetic tropolones were

thujaplicin Thujaplicins (isopropyl cycloheptatrienolones) are a series of tropolone-related chemical substances that have been isolated from the hardwoods of the trees of '' Cupressaceae'' family. These compounds are known for their antibacterial, antifung ...

s derived by

Ralph Raphael Ralph Alexander Raphael (1 January 1921 – 27 April 1998) was a British organic chemist, well known for his use of acteylene derivatives in the synthesis of natural products with biological activity. Early life and education Ralph Raphael ...

Biological effects

It is an inhibitor of

grape A grape is a fruit, botanically a berry, of the deciduous woody vines of the flowering plant genus ''Vitis''. Grapes are a non- climacteric type of fruit, generally occurring in clusters. The cultivation of grapes began perhaps 8,000 years ago, ...

polyphenol oxidase Polyphenol oxidase (PPO; also polyphenol oxidase i, chloroplastic), an enzyme involved in fruit browning, is a tetramer that contains four atoms of copper per molecule. PPO may accept monophenols and/or ''o''-diphenols as substrates. The ...

and mushroom

tyrosinase Tyrosinase is an oxidase that is the rate-limiting enzyme for controlling the production of melanin. The enzyme is mainly involved in two distinct reactions of melanin synthesis otherwise known as the Raper Mason pathway. Firstly, the hydroxylat ...

.Inhibition of mushroom tyrosinase by tropolone. Varda Kahn and Andrawis Andrawis, Phytochemistry, Volume 24, Issue 5, 1985, Pages 905-908,

Tropolone derivatives

References

{{Monoamine metabolism modulators Dopamine beta hydroxylase inhibitors Vinylogous carboxylic acids