Tropolone is an organic compound 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, it can be viewed as its derivative with a hydroxyl group in the 2-position.
Many methods have been described for the synthesis of tropolone.[1] 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.[2]
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:[1]
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.[2]
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 complex.[2]
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.[3]
Around 200 naturally occurring tropolone derivatives have been isolated, mostly from plants and fungi.[4] [5] [6] [7] Tropolone compounds and their derivatives include (such as and derivatives and others.[8] Tropolone arises via a polyketide pathway, which affords a phenolic intermediate that undergoes ring expansion.[9]
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.[10] 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.[11]
| Name | Chemical structure | Natural sources | |
|---|---|---|---|
| Tropolone | Pseudomonas lindbergii, Pseudomonas plantarii[12] [13] [14] and mushroom tyrosinase.[15] | ||
| Hinokitiol | Cupressaceae trees[16] | ||
| Stipitatic acid | Talaromyces stipitatus[17] | ||
| Colchicine | Colchicum autumnale, Gloriosa superba[18] |
| Class | Examples | Main natural sources[19] [20] | Research directions[21] [22] [23] | Patented in products[24] | |
|---|---|---|---|---|---|
| Simple tropolones | Tropolone | Pseudomonas 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 | - | |
| Dolabrins | β-dolabrin, α-dolabrinol | Caragana pygmaea, Cupressus goveniana, Cupressus abramsiana, Thujopsis dolabrata | Antibacterial, antifungal, insecticidal, pesticidal, plant growth inhibition, protease inhibition | Insect 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 medicine | Insect repellent, deodorant, toothpaste, oral spray, skin and hair care, wood preservative, food additive, food packaging | |
| Sesquiterpene tropolones | Nootkatin, nootkatinol, nootkatol, nootkatene, valencene-13-ol, nootkastatin | Chamaecyparis nootkatensis, Grapefruit | Antifungal, anti-browning (anti-tyrosinase), insecticidal, fungicidal, antineoplastic | Insect repellents, flavor, perfumery | |
| Pygmaeins | Pygmaein, 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, antiviral | Food additive | |
| Theaflavins | Theaflavin, theaflavic acid, theaflavate A and B | Camellia sinensis, Quercus species | Antibacterial, anti-inflammatory, antioxidant, antiviral, antidiabetic, chemosensitizing | - | |
| Tropoisoquinolines and tropoloisoquinolines | Grandirubrine, imerubrine, isoimerubrine, pareitropone, pareirubrine A and B | Cissampelos pareira, Abuta grandifolia | Antileukemic | - | |
| Tropone alkaloids | Colchicine, demecolcine | Colchicum autumnale, Gloriosa superba | Antimitotic, anti-inflammatory, anti-gout, plant breeding | Pharmaceutical drug |