Tropolone

Last updated

Contents

Tropolone [1]
Skeletal formula of tropolone Tropolone.png
Skeletal formula of tropolone
Space-filling model of tropolone Tropolone-3D-spacefill.png
Space-filling model of tropolone
Names
Preferred IUPAC name
2-Hydroxycyclohepta-2,4,6-trien-1-one
Other names
2-Hydroxytropone; Purpurocatechol
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
ECHA InfoCard 100.007.799 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 208-577-2
KEGG
MeSH D014334
PubChem CID
UNII
  • InChI=1S/C7H6O2/c8-6-4-2-1-3-5-7(6)9/h1-5H,(H,8,9) X mark.svgN
    Key: MDYOLVRUBBJPFM-UHFFFAOYSA-N X mark.svgN
  • InChI=1/C7H6O2/c8-6-4-2-1-3-5-7(6)9/h1-5H,(H,8,9)
    Key: MDYOLVRUBBJPFM-UHFFFAOYAW
  • C1=CC=C(C(=O)C=C1)O
Properties
C7H6O2
Molar mass 122.12 g/mol
Melting point 50 to 52 °C (122 to 126 °F; 323 to 325 K)
Boiling point 80 to 84 °C (176 to 183 °F; 353 to 357 K) (0.1 mmHg)
Acidity (pKa)6.89 (and -0.5 for conjugate acid)
-61·10−6 cm3/mol
Hazards
GHS labelling: [2]
GHS-pictogram-acid.svg GHS-pictogram-exclam.svg GHS-pictogram-pollu.svg
Danger
H314, H317, H410
P260, P261, P264, P272, P273, P280, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P333+P313, P363, P391, P405, P501
Flash point 112 °C (234 °F; 385 K)
Related compounds
Related compounds
 Hinokitiol (4-isopropyl-tropolone)
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
X mark.svgN  verify  (what is  Yes check.svgYX mark.svgN ?)

Tropolone is an organic compound with the chemical formula C7H5(OH)O. 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, it can be viewed as its derivative with a hydroxyl group in the 2-position.

Synthesis and reactions

Many methods have been described for the synthesis of tropolone. [3] 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. [4]

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: [3]

OS tropolone from CpH.svg

Thy hydroxyl group of tropolone is acidic, having a pKa 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. [4]

The compound readily undergoes O-alkylation to give cycloheptatrienyl derivatives, which in turn are versatile synthetic intermediates. [5] With metal cations, it undergoes deprotonation to form a bidentate ligand, such as in the Cu(O2C7H5)2 complex. [4]

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. [6]

TropoloneTaut.svg

Natural occurrence

Around 200 naturally occurring tropolone derivatives have been isolated, mostly from plants and fungi. [7] [8] [9] [10] Tropolone compounds and their derivatives include dolabrins, dolabrinols, thujaplicins , thujaplicinols, stipitatic acid , stipitatonic acid, nootkatin, nootkatinol, puberulic acid , puberulonic acid, sepedonin, 4-acetyltropolone, pygmaein, isopygmaein, procein, chanootin, benzotropolones (such as purpurogallin , crocipodin, goupiolone A and B), theaflavin and derivatives bromotropolones, tropoisoquinolines and tropoloisoquinolines (such as grandirubrine, imerubrine, isoimerubrine, pareitropone, pareirubrine A and B), colchicine , colchicone and others. [11] Tropolone arises via a polyketide pathway, which affords a phenolic intermediate that undergoes ring expansion. [5]

They are especially found in specific plant species, such as Cupressaceae and Liliaceae families. [9] 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. [12] 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. [13]

Tropolone derivatives

NameChemical structureNatural sources
Tropolone
Tropolone.png
Pseudomonas lindbergii, Pseudomonas plantarii [14] [15] [16] and mushroom tyrosinase. [17]
Hinokitiol
Gamma-thujaplicin.png
Cupressaceae trees [18]
Stipitatic acid
Stipitatic acid.svg
Talaromyces stipitatus [19]
Colchicine
Colchicin.svg
Colchicum autumnale , Gloriosa superba [20]
ClassExamplesMain natural sources [11] [9] [21] [22] Research directions [9] [23] [11] [24] [25] Patented in products [9] [26]
Simple tropolonesTropolonePseudomonas lindbergii, Pseudomonas plantarii Antibacterial, antifungal, insecticidal, pesticidal, plant growth inhibition, anti-inflammatory, antioxidant, neuroprotection, anti-protease, anti-browning (anti-tyrosinase and anti-polyphenol oxidase), antineoplastic, chelating-
Dolabrinsβ-dolabrin, α-dolabrinol Caragana pygmaea , Cupressus goveniana , Cupressus abramsiana , Thujopsis dolabrata Antibacterial, antifungal, insecticidal, pesticidal, plant growth inhibition, protease inhibitionInsect repellent, deodorant
Thujaplicins α-thujaplicin, β-thujaplicin (hinokitiol), γ-thujaplicin, thujaplicinol Chamaecyparis obtusa , Thuja plicata , Thujopsis dolabrata , Juniperus cedrus , Cedrus atlantica , Cupressus lusitanica , Chamaecyparis lawsoniana , Chamaecyparis taiwanensis , Chamaecyparis thyoides , Cupressus arizonica , Cupressus macnabiana , Cupressus macrocarpa , Cupressus guadalupensis , Juniperus chinensis , Juniperus communis , Juniperus californica , Juniperus occidentalis , Juniperus oxycedrus , Juniperus sabina , Calocedrus decurrens , Calocedrus formosana , Platycladus orientalis , Thuja occidentalis , Thuja standishii , Tetraclinis articulata , Cattleya forbesii , Carya glabra Antifungal, antibacterial, anti-browning (anti-tyrosinase), chelating, insecticidal, pesticidal, antimalarial, antiviral, anti-inflammatory, plant growth inhibition, anti-protease, antidiabetic, antineoplastic, chemosensitizing, antioxidant, neuroprotection, veterinary medicineInsect repellent, deodorant, toothpaste, oral spray, skin and hair care, wood preservative, food additive, food packaging
Sesquiterpene tropolonesNootkatin, nootkatinol, nootkatol, nootkatene, valencene-13-ol, nootkastatin Chamaecyparis nootkatensis , Grapefruit Antifungal, anti-browning (anti-tyrosinase), insecticidal, fungicidal, antineoplasticInsect repellents, flavor, perfumery
PygmaeinsPygmaein, Isopygmaein Caragana pygmaea , Cupressus goveniana , Cupressus abramsiana --
Benzotropolones Purpurogallin, crocipodin, goupiolone A and B Quercus species, Leccinum crocipodium , Goupia glabra Antibacterial, plant growth inhibition, protease inhibition, antineoplastic, antimalarial, antioxidant, antiviralFood additive
Theaflavins Theaflavin, theaflavic acid, theaflavate A and B Camellia sinensis , Quercus speciesAntibacterial, anti-inflammatory, antioxidant, antiviral, antidiabetic, chemosensitizing-
Tropoisoquinolines and tropoloisoquinolinesGrandirubrine, imerubrine, isoimerubrine, pareitropone, pareirubrine A and B Cissampelos pareira , Abuta grandifoliaAntileukemic-
Tropone alkaloids Colchicine, demecolcine Colchicum autumnale , Gloriosa superba Antimitotic, anti-inflammatory, anti-gout, plant breedingPharmaceutical drug

Related Research Articles

<span class="mw-page-title-main">Aromatic compound</span> Compound containing rings with delocalized pi electrons

Aromatic compounds or arenes usually refers to organic compounds "with a chemistry typified by benzene" and "cyclically conjugated." The word "aromatic" originates from the past grouping of molecules based on odor, before their general chemical properties were understood. The current definition of aromatic compounds does not have any relation to their odor. Aromatic compounds are now defined as cyclic compounds satisfying Hückel's Rule. Aromatic compounds have the following general properties:

<span class="mw-page-title-main">Alkaloid</span> Class of naturally occurring chemical compounds

Alkaloids are a class of basic, naturally occurring organic compounds that contain at least one nitrogen atom. This group also includes some related compounds with neutral and even weakly acidic properties. Some synthetic compounds of similar structure may also be termed alkaloids. In addition to carbon, hydrogen and nitrogen, alkaloids may also contain oxygen or sulfur. Rarer still, they may contain elements such as phosphorus, chlorine, and bromine.

<span class="mw-page-title-main">Phenols</span> Chemical compounds in which hydroxyl group is attached directly to an aromatic ring

In organic chemistry, phenols, sometimes called phenolics, are a class of chemical compounds consisting of one or more hydroxyl groups bonded directly to an aromatic hydrocarbon group. The simplest is phenol, C
6H
5OH. Phenolic compounds are classified as simple phenols or polyphenols based on the number of phenol units in the molecule.

<span class="mw-page-title-main">Tyrosine</span> Amino acid

L-Tyrosine or tyrosine or 4-hydroxyphenylalanine is one of the 20 standard amino acids that are used by cells to synthesize proteins. It is a conditionally essential amino acid with a polar side group. The word "tyrosine" is from the Greek tyrós, meaning cheese, as it was first discovered in 1846 by German chemist Justus von Liebig in the protein casein from cheese. It is called tyrosyl when referred to as a functional group or side chain. While tyrosine is generally classified as a hydrophobic amino acid, it is more hydrophilic than phenylalanine. It is encoded by the codons UAC and UAU in messenger RNA.

<i>Thuja plicata</i> Species of conifer

Thuja plicata is a large evergreen coniferous tree in the family Cupressaceae, native to the Pacific Northwest of North America. Its common name is western redcedar in the U.S. or western red cedar in the UK, and it is also called pacific red cedar, giant arborvitae, western arborvitae, just cedar, giant cedar, or shinglewood. It is not a true cedar of the genus Cedrus. T. plicata is the largest species in the genus Thuja, growing up to 70 metres (230 ft) tall and 7 m (23 ft) in diameter. It mostly grows in areas that experience a mild climate with plentiful rainfall, although it is sometimes present in drier areas on sites where water is available year-round, such as wet valley bottoms and mountain streamsides. The species is shade-tolerant and able to establish in forest understories and is thus considered a climax species. It is a very long-lived tree, with some specimens reaching ages of well over 1,000 years.

<span class="mw-page-title-main">Azulene</span> Chemical compound

Azulene is an aromatic organic compound and an isomer of naphthalene. Naphthalene is colourless, whereas azulene is dark blue. The compound is named after its colour, as "azul" is Spanish for blue. Two terpenoids, vetivazulene (4,8-dimethyl-2-isopropylazulene) and guaiazulene (1,4-dimethyl-7-isopropylazulene), that feature the azulene skeleton are found in nature as constituents of pigments in mushrooms, guaiac wood oil, and some marine invertebrates.

<span class="mw-page-title-main">Natural product</span> Chemical compound or substance produced by a living organism, found in nature

A natural product is a natural compound or substance produced by a living organism—that is, found in nature. In the broadest sense, natural products include any substance produced by life. Natural products can also be prepared by chemical synthesis and have played a central role in the development of the field of organic chemistry by providing challenging synthetic targets. The term natural product has also been extended for commercial purposes to refer to cosmetics, dietary supplements, and foods produced from natural sources without added artificial ingredients.

<span class="mw-page-title-main">Phenazine</span> Chemical compound

Phenazine is an organic compound with the formula (C6H4)2N2. It is a dibenzo annulated pyrazine, and the parent substance of many dyestuffs, such as the toluylene red, indulines, and safranines (and the closely related eurhodines). Phenazine crystallizes in yellow needles, which are only sparingly soluble in alcohol. Sulfuric acid dissolves it, forming a deep-red solution.

Guaiacol is an organic compound with the formula C6H4(OH)(OCH3). It is a phenolic compound containing a methoxy functional group. Guaiacol appears as a viscous colorless oil, although aged or impure samples are often yellowish. It occurs widely in nature and is a common product of the pyrolysis of wood.

<span class="mw-page-title-main">Dakin oxidation</span> Organic redox reaction that converts hydroxyphenyl aldehydes or ketones into benzenediols

The Dakin oxidation (or Dakin reaction) is an organic redox reaction in which an ortho- or para-hydroxylated phenyl aldehyde (2-hydroxybenzaldehyde or 4-hydroxybenzaldehyde) or ketone reacts with hydrogen peroxide (H2O2) in base to form a benzenediol and a carboxylate. Overall, the carbonyl group is oxidised, whereas the H2O2 is reduced.

<span class="mw-page-title-main">Dirigent protein</span>

Dirigent proteins are members of a class of proteins which dictate the stereochemistry of a compound synthesized by other enzymes. The first dirigent protein was discovered in Forsythia intermedia. This protein has been found to direct the stereoselective biosynthesis of (+)-pinoresinol from coniferyl alcohol monomers:

<span class="mw-page-title-main">Boronic acid</span> Organic compound of the form R–B(OH)2

A boronic acid is an organic compound related to boric acid in which one of the three hydroxyl groups is replaced by an alkyl or aryl group. As a compound containing a carbon–boron bond, members of this class thus belong to the larger class of organoboranes.

<span class="mw-page-title-main">Tropone</span> Chemical compound

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. The related compound tropolone (2-hydroxy-2,4,6-cycloheptatrien-1-one) has an additional alcohol group next to the ketone. Tropones are uncommon in natural products, with the notable exception of the 2-hydroxyl derivatives, which are called tropolones.

<span class="mw-page-title-main">Pancratistatin</span> Chemical compound

Pancratistatin (PST) is a natural compound initially extracted from spider lily, a Hawaiian native plant of the family Amaryllidaceae (AMD).

<span class="mw-page-title-main">Thujaplicin</span> Chemical compound

Thujaplicin is any of three isomeric tropolone-related natural products that have been isolated from the softwoods of the trees of Cupressaceae family. These compounds are known for their antibacterial, antifungal, and antioxidant properties. They were the first natural tropolones to be made synthetically.

<span class="mw-page-title-main">Procyanidin C2</span> Chemical compound

Procyanidin C2 is a B type proanthocyanidin trimer, a type of condensed tannin.

<span class="mw-page-title-main">Hinokitiol</span> Chemical compound

Hinokitiol (β-thujaplicin) is a natural monoterpenoid found in the wood of trees in the family Cupressaceae. It is a tropolone derivative and one of the thujaplicins. Hinokitiol is used in oral and skin care products, and is a food additive used in Japan.

<span class="mw-page-title-main">Totarol</span> Chemical compound

Totarol is a naturally produced diterpene that is bioactive as totarol. It was first isolated by McDowell and Easterfield from the heartwood of Podocarpus totara, a conifer tree found in New Zealand. Podocarpus totara was investigated for unique molecules due to the tree's increased resistance to rotting. Recent studies have confirmed totarol's unique antimicrobial and therapeutic properties. Consequently, totarol is a candidate for a new source of drugs and has been the goal of numerous syntheses.

<span class="mw-page-title-main">Syringic acid</span> Chemical compound

Syringic acid is a naturally occurring phenolic compound and dimethoxybenzene that is commonly found as a plant metabolite.

<span class="mw-page-title-main">Tetsuo Nozoe</span>

Tetsuo Nozoe was a Japanese organic chemist. He is known for the discovery of hinokitiol, a seven-membered aromatic compound, and studying non-benzenoid aromatic compounds.

References

  1. ↑ Tropolone [ permanent dead link ] at Sigma-Aldrich
  2. ↑ "Tropolone". pubchem.ncbi.nlm.nih.gov.
  3. 1 2 Minns RA (1977). "Tropolone". Org. Synth. 57: 117. doi:10.15227/orgsyn.057.0117.
  4. 1 2 3 Pauson PL (1955). "Tropones and Tropolones". Chem. Rev. 55 (1): 9–136. doi:10.1021/cr50001a002.
  5. 1 2 Pietra F (1973). "Seven-membered conjugated carbo- and heterocyclic compounds and their homoconjugated analogs and metal complexes. Synthesis, biosynthesis, structure, and reactivity". Chemical Reviews. 73 (4): 293–364. doi:10.1021/cr60284a002.
  6. ↑ Jin L (February 1987). Detoxification of thujaplicins in living western red cedar (Thuja plicata Donn.) trees by microorganisms (PhD). University of British Columbia.
  7. ↑ Bentley R (2008). "A fresh look at natural tropolonoids". Nat. Prod. Rep. 25 (1): 118–138. doi:10.1039/b711474e. PMID   18250899.
  8. ↑ Guo H, Roman D, Beemelmanns C (2019). "Tropolone natural products". Natural Product Reports. 36 (8): 1137–1155. doi:10.1039/c8np00078f. PMID   30556819.
  9. 1 2 3 4 5 Zhao JZ (30 September 2007). "Plant Troponoids: Chemistry, Biological Activity, and Biosynthesis". Current Medicinal Chemistry. 14 (24): 2597–2621. doi:10.2174/092986707782023253. PMID   17979713.
  10. ↑ Bentley R (2008). "A fresh look at natural tropolonoids". Nat. Prod. Rep. 25 (1): 118–138. doi:10.1039/b711474e. PMID   18250899.
  11. 1 2 3 Liu N, Song W, Schienebeck CM, Zhang M, Tang W (December 2014). "Synthesis of naturally occurring tropones and tropolones". Tetrahedron. 70 (49): 9281–9305. doi:10.1016/j.tet.2014.07.065. PMC   4228802 . PMID   25400298.
  12. ↑ Nakanishi K (June 2013). "Tetsuo Nozoe's "Autograph Books by Chemists 1953-1994": An Essay: Tetsuo Nozoe's "Autograph Books by Chemists 1953-1994": An Essay". The Chemical Record. 13 (3): 343–352. doi: 10.1002/tcr.201300007 . PMID   23737463.
  13. ↑ Cook JW, Raphael RA, Scott AI (1951). "149. Tropolones. Part II. The synthesis of α-, β-, and γ-thujaplicins". J. Chem. Soc.: 695–698. doi:10.1039/JR9510000695.
  14. ↑ Liu N, Song W, Schienebeck CM, Zhang M, Tang W (December 2014). "Synthesis of naturally occurring tropones and tropolones". Tetrahedron. 70 (49): 9281–9305. doi:10.1016/j.tet.2014.07.065. PMC   4228802 . PMID   25400298.
  15. ↑ Valero E, Garcia-Moreno M, Varon R, Garcia-Carmona F (1991). "Time-dependent inhibition of grape polyphenol oxidase by tropolone". Journal of Agricultural and Food Chemistry. 39 (6): 1043–1046. Bibcode:1991JAFC...39.1043V. doi:10.1021/jf00006a007.
  16. ↑ Chedgy, Russell. Secondary metabolites of Western red cedar (Thuja plicata): their biotechnological applications and role in conferring natural durability. LAP Lambert Academic Publishing, 2010, ISBN   3-8383-4661-0, ISBN   978-3-8383-4661-8
  17. ↑ Kahn V, Andrawis A (1985). "Inhibition of mushroom tyrosinase by tropolone". Phytochemistry. 24 (5): 905–908. Bibcode:1985PChem..24..905K. doi:10.1016/S0031-9422(00)83150-7.
  18. ↑ Saniewski M, Horbowicz M, Kanlayanarat S (10 September 2014). "The Biological Activities of Troponoids and Their Use in Agriculture A Review". Journal of Horticultural Research. 22 (1): 5–19. doi: 10.2478/johr-2014-0001 .
  19. ↑ Davison J, al Fahad A, Cai M, Song Z, Yehia SY, Lazarus CM, Bailey AM, Simpson TJ, Cox RJ (15 May 2012). "Genetic, molecular, and biochemical basis of fungal tropolone biosynthesis". Proceedings of the National Academy of Sciences. 109 (20): 7642–7647. doi: 10.1073/pnas.1201469109 . PMC   3356636 . PMID   22508998.
  20. ↑ Keith MP, Gilliland WR, Uhl K (2009). "GOUT". Pharmacology and Therapeutics: 1039–1046. doi:10.1016/B978-1-4160-3291-5.50079-2. ISBN   978-1-4160-3291-5.
  21. ↑ Karchesy JJ, Kelsey RG, González-Hernández MP (May 2018). "Yellow-Cedar, Callitropsis (Chamaecyparis) nootkatensis, Secondary Metabolites, Biological Activities, and Chemical Ecology". Journal of Chemical Ecology. 44 (5): 510–524. Bibcode:2018JCEco..44..510K. doi:10.1007/s10886-018-0956-y. PMID   29654493. S2CID   4839697.
  22. ↑ Goldfrank's toxicologic emergencies. Nelson, Lewis, 1963- (Eleventh ed.). New York. 11 April 2019. ISBN   978-1-259-85961-8. OCLC   1020416505.{{cite book}}: CS1 maint: location missing publisher (link) CS1 maint: others (link)
  23. ↑ Carlsson B, Erdtman H, Frank A, Harvey WE, Östling S (1952). "The Chemistry of the Natural Order Cupressales. VIII. Heartwood Constituents of Chamaecyparis nootkatensis - Carvacrol, Nootkatin, and Chamic Acid". Acta Chemica Scandinavica. 6: 690–696. doi: 10.3891/acta.chem.scand.06-0690 .
  24. ↑ Dalbeth N, Lauterio TJ, Wolfe HR (October 2014). "Mechanism of Action of Colchicine in the Treatment of Gout". Clinical Therapeutics. 36 (10): 1465–1479. doi: 10.1016/j.clinthera.2014.07.017 . PMID   25151572.
  25. ↑ Griffiths AJ, Gelbart WM, Miller JH (1999). "Modern Genetic Analysis: Changes in Chromosome Number". Modern Genetic Analysis. W. H. Freeman, New York.
  26. ↑ US EPA O (10 August 2020). "Nootkatone Now Registered by EPA". US EPA.
This page is based on this Wikipedia article
Text is available under the CC BY-SA 4.0 license; additional terms may apply.
Images, videos and audio are available under their respective licenses.