Phloroglucinol
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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
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Identifiers | |||
3D model (
JSmol ) |
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ChEBI | |||
ChEMBL | |||
ChemSpider | |||
ECHA InfoCard
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100.003.284 | ||
EC Number |
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KEGG | |||
PubChem CID
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RTECS number
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UNII | |||
CompTox Dashboard (EPA)
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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 in diethyl ether, ethanol, pyridine | ||
Acidity (pKa) | 8.45 | ||
-73.4·10−6 cm3/mol | |||
Pharmacology | |||
A03AX12 (WHO) | |||
Hazards | |||
GHS labelling: | |||
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)
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5 g/kg (rat, oral) | ||
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Phloroglucinol is an
Synthesis and occurrence
In 1855, phloroglucinol was first prepared from phloretin by the Austrian chemist Heinrich 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 from trinitrobenzene.[4]
The synthesis is noteworthy because ordinary aniline derivatives are unreactive toward hydroxide. Because the triaminobenzene also exists as its imine tautomer, it is susceptible to hydrolysis.
Reactions
Tautomerism and acid-base behavior
Phloroglucinol is a weak triprotic acid. The first two pKa's are 8.5 and 8.9.
As an enol, phloroglucinol in principle exists in equilibrium with keto tautomers. Evidence for this equilibrium is provided by the formation of the oxime:
- C6H3(OH)3 + 3 NH2OH → (CH2)3(C=NOH)3 + 3 H2O
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]
Other reactions
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.
The Hoesch reaction allows the synthesis of 1-(2,4,6-Trihydroxyphenyl)ethanone from phloroglucinol.[6]
Leptospermone can be synthesized from phloroglucinol by a reaction with isovaleroylnitrile in the presence of a zinc chloride catalyst.
Pentacarbon dioxide, described in 1988 by Günter Maier and others, can be obtained by pyrolysis 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 and phloretic acid gives 30% yield of phloretin[citation needed].
Natural occurrences
Phloroglucinol is also generally found in the
Phloroglucinols are secondary metabolites that occur naturally in certain plant species. It is also produced by brown algae and bacteria.
The bacterium
Biosynthesis
In
The enzyme
The enzyme phloroglucinol reductase uses dihydrophloroglucinol and NADP+ to produce phloroglucinol, NADPH, and H+. It is found in the bacterium species Eubacterium oxidoreducens.
The legume-root nodulating, microsymbiotic nitrogen-fixing bacterium species Bradyrhizobium japonicum is able to degrade catechin with formation of phloroglucinol carboxylic acid, further decarboxylated to phloroglucinol, which is dehydroxylated to resorcinol and hydroxyquinol.
Health effects
In some countries and in veterinary medicine, phloroglucinol is used as a treatment for gallstones, 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 by
Phloroglucinols acylated derivatives have a fatty acid synthase inhibitory activity.[11]
ATC classification
It has the A03AX12 code in the A03AX Other drugs for functional bowel disorders section of the ATC code A03 Drugs for functional gastrointestinal disorders subgroup of the Anatomical Therapeutic Chemical Classification System. It also has the D02.755.684 code in the D02 Organic chemicals section of the Medical Subject Headings (MeSH) codes by the United States National Library of Medicine.
Applications
Phloroglucinol is mainly used as a coupling agent in printing. It links
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 study
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]
Use in tests
Phloroglucinol is a reagent of the Tollens' test for pentoses. This test relies on reaction of the furfural 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 of
It is also part of Gunzburg reagent, an alcoholic solution of phloroglucinol and vanillin, for the qualitative detection of free hydrochloric acid in gastric juice.
References
- . On p. 120, Hlasiwetz named phloroglucin: "Die auffallendste Eigenschaft dieses Körpers ist, daſs er überaus süſs schmeckt, weſshalb er bis auf weiteres Phloroglucin genannt sein mag." (The most striking property of this substance is that it tastes extremely sweet, for which reason it may be named "phloroglucin" until further [information emerges].)
- ^ Thorpe, Edward, ed., A Dictionary of Applied Chemistry (London, England: Longmans, Green, and Co., 1913), vol. 4, 183.
- .
- ^ ISBN 978-3527306732.
- .
- .
- .
- ^ Gmelin, Leopold (1862). Watts, Henry (ed.). Hand-Book of Chemistry, Volume 15 (1st ed.). London: The Cavendish Society. Retrieved 26 December 2016.
- ^ a b Roscoe, H.E.; Schorlemmer, C. (1893). A Treatise on Chemistry, Volume 3, Part 3 (1st ed.). New York: D Appleton and Company. pp. 193 & 253. Retrieved 26 December 2016.
- ^ C. Michael Hogan (December 14, 2008). "Coastal Woodfern (Dryopteris arguta)". GlobalTwitcher. Archived from the original on 2011-07-11.
{{cite web}}
: CS1 maint: unfit URL (link) - ^ PMID 16870425.
- PMID 10913843.
- PMID 14738398.
- .
- S2CID 13479924.
- ^ PMID 15826166.
- ^ "Phloroglucinol Summary Report" (PDF). EMEA. Archived from the original (PDF) on 10 July 2007. Retrieved 24 April 2009.
- S2CID 4700542.
- S2CID 201103441.
- PMID 36443585.
- ^ "Intermediate Pharmaceutical Ingredients - Flopropione" (PDF). Univar Canada. Retrieved 24 April 2009.
- ^ "Synthesis of trinitrophloroglucinol". The United States Patent and Trademark Office. 1984. Retrieved 24 April 2009.
- ^ A facile two-step Synthesis of 1,3,5-trinitrobenzene. Bottaro Jeffrey C, Malhotra Ripudaman and Dodge Allen, Synthesis, 2004, no 4, pages 499-500, INIST 15629637
- S2CID 6585979.
- S2CID 15470904.
- ^ Oshitna, K., and Tollens, B., Ueber Spectral-reactionen des Methylfurfurols. Ber. Dtsch. Chem. Ges. 34, 1425 (1901)
- ^ Lignin production and detection in wood. John M. Harkin, U.S. Forest Service Research Note FPL-0148, November 1966 (article)