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| Names | |||
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| Preferred IUPAC name Benzene-1,3,5-triol | |||
| Other names phloroglucine,1,3,5-benzenetriol , 1,3,5-trihydroxybenzene or cyclohexane-1,3,5-trione | |||
| Identifiers | |||
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3D model (JSmol) | |||
| ChEBI | |||
| ChEMBL | |||
| ChemSpider |
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| ECHA InfoCard | 100.003.284 | ||
| EC Number |
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| KEGG | |||
| RTECS number |
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| UNII | |||
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| Properties | |||
| C6H6O3 | |||
| Molar mass | 126.11 g/mol | ||
| Appearance | colorless to beige solid | ||
| Melting point | 219 °C (426 °F; 492 K) | ||
| 1 g/100 mL | |||
| Solubility | soluble indiethyl ether,ethanol,pyridine | ||
| Acidity (pKa) | 8.45 | ||
| −73.4·10−6 cm3/mol | |||
| Pharmacology | |||
| A03AX12 (WHO) | |||
| Hazards | |||
| GHS labelling: | |||
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| Warning | |||
| H315,H317,H319,H335,H341,H361 | |||
| P201,P202,P261,P264,P271,P272,P280,P281,P302+P352,P304+P340,P305+P351+P338,P308+P313,P312,P321,P332+P313,P333+P313,P337+P313,P362,P363,P403+P233,P405,P501 | |||
| Lethal dose or concentration (LD, LC): | |||
LD50 (median dose) | 5 g/kg (rat, oral) | ||
Except where otherwise noted, data are given for materials in theirstandard state (at 25 °C [77 °F], 100 kPa). | |||
Phloroglucinol is anorganic compound with the formula C6H3(OH)3. It is a colorless solid. It is used in thesynthesis ofpharmaceuticals andexplosives. Phloroglucinol is one of three isomericbenzenetriols. The other two isomers arehydroxyquinol (1,2,4-benzenetriol) andpyrogallol (1,2,3-benzenetriol). Phloroglucinol, and its benzenetriol isomers, are still defined as "phenols" according to theIUPAC official nomenclature rules of chemical compounds. Many such monophenolics are often termedpolyphenols.
In 1855, phloroglucinol was first prepared fromphloretin by the Austrian chemistHeinrich Hlasiwetz (1825–1875).[1][2]
A modern synthesis of phloroglucinol involves hydrolysis of benzene-1,3,5-triamine and its derivatives.[3] Representative is the following route fromtrinitrobenzene.[4]
The synthesis is noteworthy because ordinaryaniline derivatives are unreactive towardhydroxide. Because the triaminobenzene also exists as itsimine tautomer, it is susceptible tohydrolysis.
Phloroglucinol is a weak triprotic acid. The first two pKa's are 8.5 and 8.9.
As anenol, phloroglucinol in principle exists in equilibrium with ketotautomers. Evidence for this equilibrium is provided by the formation of theoxime:
But it behaves also like a benzenetriol as the three hydroxyl groups can be methylated to give 1,3,5-trimethoxybenzene.[4]
For the neutral compound, the keto tautomers are undetectable spectroscopically. Upon deprotonation, the keto tautomer predominates.[5]
From water, phloroglucinol crystallizes as the dihydrate, which has a melting point of 116–117 °C, but the anhydrous form melts at a much higher temperature, at 218–220 °C. It does not boil intact, but it does sublime.
TheHoesch reaction allows the synthesis of1-(2,4,6-Trihydroxyphenyl)ethanone from phloroglucinol.[6]
Leptospermone can be synthesized from phloroglucinol by a reaction withisovaleroylnitrile in the presence of a zinc chloride catalyst.
Pentacarbon dioxide, described in 1988 byGünter Maier and others, can be obtained bypyrolysis of 1,3,5-cyclohexanetrione (phloroglucin).[7]
Phloroglucinol readily forms 5-aminoresorcinol (aka Phloramine) in aqueous ammonia at low temperatures.[8][9]
Reaction of phloroglucinol andphloretic acid gives 30% yield ofphloretin[citation needed].
Phloroglucinol is also generally found in theflavonoid ring A substitution pattern. Indeed, it was originally prepared fromphloretin, a compound isolated from fruit trees, usingpotassium hydroxide.[9] Additionally, the compound can be similarly prepared fromglucosides, plant extracts andresins such asquercetin,catechin andphlobaphenes.
Phloroglucinols aresecondary metabolites that occur naturally in certain plant species. It is also produced by brown algae and bacteria.
Acyl derivatives are present in the fronds of the coastal woodfern,Dryopteris arguta[10] or inDryopteris crassirhizoma.[11] The anthelmintic activity of the root ofDryopteris filix-mas has been claimed to be due toflavaspidic acid, a phloroglucinol derivative.
Formylated phloroglucinol compounds (euglobals,macrocarpals andsideroxylonals) can be found inEucalyptus species.[12]Hyperforin andadhyperforin are two phloroglucinols found inSt John's wort.Humulone is a phloroglucinol derivative with threeisoprenoid side-chains. Two side-chains are prenyl groups and one is an isovaleryl group. Humulone is a bitter-tasting chemical compound found in the resin of mature hops (Humulus lupulus).
Brown algae, such asEcklonia stolonifera,Eisenia bicyclis[13] or species in the genusZonaria,[14] produce phloroglucinol and phloroglucinol derivatives. Brown algae also produce a type of tannins known asphlorotannins.[15]
The bacteriumPseudomonas fluorescens produces phloroglucinol,phloroglucinol carboxylic acid anddiacetylphloroglucinol.[16]
InPseudomonas fluorescens, biosynthesis of phloroglucinol is performed with atype III polyketide synthase. The synthesis begins with the condensation of threemalonyl-CoAs. Then decarboxylation followed by the cyclization of the activated3,5-diketoheptanedioate product leads to the formation of phloroglucinol.[16]
The enzymepyrogallol hydroxytransferase uses1,2,3,5-tetrahydroxybenzene and1,2,3-trihydroxybenzene (pyrogallol) to produce 1,3,5-trihydroxybenzene (phloroglucinol) and1,2,3,5-tetrahydroxybenzene. It is found in the bacterium speciesPelobacter acidigallici.
The enzymephloroglucinol reductase usesdihydrophloroglucinol and NADP+ to produce phloroglucinol, NADPH, and H+. It is found in the bacterium speciesEubacterium oxidoreducens.
The legume-root nodulating, microsymbiotic nitrogen-fixing bacterium speciesBradyrhizobium japonicum is able to degradecatechin with formation ofphloroglucinol carboxylic acid, further decarboxylated to phloroglucinol, which is dehydroxylated toresorcinol andhydroxyquinol.
Phloretin hydrolase usesphloretin and water to producephloretate and phloroglucinol.
In some countries and in veterinary medicine, phloroglucinol is used as a treatment forgallstones,spasmodic pain and other related gastrointestinal disorders[17]A 2018 review found insufficient evidence that phloroglucinol was effective for treating abdominal pain[18]A 2020 review found insufficient evidence that phloroglucinol was effective for treating pain caused byobstetric andgynecological conditions.[19] A 2022 phase 3 study conducted in Italy on 364 patients indicated phloroglucinol and its derivative must be as effective asnonsteroidal anti-inflammatory drugs for the treatment of pain and spasms of biliary or urinary tracts.[20]
Phloroglucinols acylated derivatives have afatty acid synthase inhibitory activity.[11]
It has the A03AX12 code in the A03AXOther drugs for functional bowel disorders section of theATC code A03 Drugs for functional gastrointestinal disorders subgroup of the Anatomical Therapeutic Chemical Classification System. It also has the D02.755.684 code in theD02Organic chemicals section of the Medical Subject Headings (MeSH) codes by the United States National Library of Medicine.
Phloroglucinol is mainly used as a coupling agent in printing. It linksdiazo dyes to give a fast black.
It is useful for the industrial synthesis of pharmaceuticals (Flopropione[21]),Phloretin, and explosives (TATB (2,4,6-triamino-1,3,5-trinitrobenzene),trinitrophloroglucinol,[22]1,3,5-trinitrobenzene[23]).
Phloroglucinolysis is an analytical technique to studycondensed tannins by means ofdepolymerisation. The reaction makes use of phloroglucinol asnucleophile.Phlobaphenes formation (tannins condensation and precipitation) can be minimized in using strong nucleophiles, such as phloroglucinol, during pine tannins extraction.[24]
Phloroglucinol is used in plant culture media. It demonstrates both cytokinin-like and auxin-like activity. Phloroglucinol increases shoot formation and somatic embryogenesis in several horticultural and grain crops. When added to rooting media together with auxin, phloroglucinol further stimulates rooting.[25]
Phloroglucinol is a reagent of theTollens' test forpentoses. This test relies on reaction of thefurfural with phloroglucinol to produce a colored compound with high molar absorptivity.[26]
A solution of hydrochloric acid and phloroglucinol is also used for the detection oflignin (Wiesner test). A brilliant red color develops, owing to the presence ofconiferaldehyde groups in the lignin.[27] A similar test can be performed withtolonium chloride.
It is also part ofGunzburg reagent, an alcoholic solution of phloroglucinol andvanillin, for the qualitative detection of free hydrochloric acid in gastric juice.
