PHLOROGLUCINOL

Phloroglucinol serves as an effective multifunctional aromatic building block for producing specialty chemicals, pharmaceutical intermediates, and advanced organic compounds.
Phloroglucinol's symmetric trihydroxybenzene structure supports diverse substitution and condensation reactions, allowing flexible use across synthetic and analytical applications.
This combination of structural simplicity and broad chemical utility makes phloroglucinol valuable in fine chemical manufacturing, research, and functional material development.

CAS Number: 108-73-6
EC Number: 203-611-2
Molecular Formula: C6H6O3
Molecular Weight: 126.11 g/mol

Synonyms: 1,3,5-Benzenetriol, Benzene-1,3,5-triol, 1,3,5-Trihydroxybenzene, Phloroglucin, Phloroglucine, Sym-Trihydroxybenzene, s-Trihydroxybenzene, Benzene, trihydroxy, Benzene-s-triol, 3,5-Dihydroxyphenol, 5-Hydroxyresorcinol, 5-Oxyresorcinol, Floroglucin, Floroglucinol, Phloroglucinol anhydrous, NSC-1572, DHD7FFG6YS, CHEBI:16204, CHEMBL473159, DB12944, DTXSID9048354, HMDB0013675, D00152, J2.866E, RefChem:6129

Phloroglucinol is an organic compound with the formula C6H3(OH)3.
Phloroglucinol is a colorless solid.

Phloroglucinol is used in the synthesis of pharmaceuticals and explosives.
Phloroglucinol is one of three isomeric benzenetriols.

The other two isomers are hydroxyquinol (1,2,4-benzenetriol) and pyrogallol (1,2,3-benzenetriol).
Phloroglucinol, and its benzenetriol isomers, are still defined as "phenols" according to the IUPAC official nomenclature rules of chemical compounds.

Many such monophenolics are often termed polyphenols.
The enzyme is biosynthesized by phloroglucinol synthase.

Phloroglucinol is defined as a polyphenolic compound characterized by an aromatic phenyl ring with three hydroxyl groups, exhibiting various biological activities such as antioxidant, anti-inflammatory, and antimicrobial effects, which makes it of interest for drug development and other applications.
Phloroglucinol is an aromatic organic compound belonging to the class of benzenetriols, with three hydroxyl groups attached to a benzene ring at the 1,3,5-positions.

Phloroglucinol is widely used as a chemical intermediate in pharmaceutical, analytical, dye, resin, and specialty chemical applications.
Phloroglucinol's highly functionalized aromatic structure makes it useful in condensation reactions, synthesis of heterocyclic compounds, and the preparation of complex organic molecules.

Applications of Phloroglucinol:
Phloroglucinol is a phenol derivative that shows cyctoprotective effect from oxidative damage by enhancing the activity of cellular catalase.
Phloroglucinol can react with benzaldehyde derivatives to form phloroglucinol-based microporous polymeric organic frameworks (phlo-POF) with potential applications in ion-exchange and gas adsorption.
Phloroglucinol can also be used to prepare synthetic analogs of A-type proanthocyanidins (PACs) such as 2,8-dioxabicyclo[3.3.1]nonane derivatives by reacting with the corresponding flavylium salts.

Phloroglucinol is mainly used as a coupling agent in printing.
Phloroglucinol links diazo dyes to give a fast black.

Phloroglucinol is useful for the industrial synthesis of pharmaceuticals (Flopropione), Phloretin, and explosives (TATB (2,4,6-triamino-1,3,5-trinitrobenzene), trinitrophloroglucinol, 1,3,5-trinitrobenzene).

Phloroglucinolysis is an analytical technique to study condensed tannins by means of depolymerisation.
The reaction makes use of phloroglucinol as nucleophile.
Phlobaphenes formation (tannins condensation and precipitation) can be minimized in using strong nucleophiles, such as phloroglucinol, during pine tannins extraction.

Phloroglucinol is used in plant culture media.
Phloroglucinol 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.

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.

A solution of hydrochloric acid and phloroglucinol is also used for the detection of lignin (Wiesner test).
A brilliant red color develops, owing to the presence of coniferaldehyde groups in the lignin.
A similar test can be performed with tolonium chloride.

Phloroglucinol is also part of Gunzburg reagent, an alcoholic solution of phloroglucinol and vanillin, for the qualitative detection of free hydrochloric acid in gastric juice.

Biosynthesis of Phloroglucinol:
In Pseudomonas fluorescens, biosynthesis of phloroglucinol is performed with a type III polyketide synthase.
The synthesis begins with the condensation of three malonyl-CoAs.
Then decarboxylation followed by the cyclization of the activated 3,5-diketoheptanedioate product leads to the formation of phloroglucinol.

The enzyme pyrogallol hydroxytransferase uses 1,2,3,5-tetrahydroxybenzene and 1,2,3-trihydroxybenzene (pyrogallol) to produce 1,3,5-trihydroxybenzene (phloroglucinol) and 1,2,3,5-tetrahydroxybenzene.
Phloroglucinol is found in the bacterium species Pelobacter acidigallici.

The enzyme phloroglucinol reductase uses dihydrophloroglucinol and NADP+ to produce phloroglucinol, NADPH, and H+.
Phloroglucinol 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.

Phloretin hydrolase uses phloretin and water to produce phloretate and phloroglucinol.

Occurrence of Phloroglucinol:

Synthesis and Occurrence:
In 1855, phloroglucinol was first prepared from phloretin by the Austrian chemist Heinrich Hlasiwetz (1825–1875).

A modern synthesis of phloroglucinol involves hydrolysis of benzene-1,3,5-triamine and its derivatives.
Representative is the following route from trinitrobenzene.

The synthesis is noteworthy because ordinary aniline derivatives are unreactive toward hydroxide.
Because the triaminobenzene also exists as its imine tautomer, Phloroglucinol is susceptible to hydrolysis.

Natural Occurrences:
Phloroglucinol is also generally found in the flavonoid ring A substitution pattern.
Indeed, Phloroglucinol was originally prepared from phloretin, a compound isolated from fruit trees, using potassium hydroxide.
Additionally, the compound can be similarly prepared from glucosides, plant extracts and resins such as quercetin, catechin and phlobaphenes.

Phloroglucinols are secondary metabolites that occur naturally in certain plant species.
Phloroglucinol is also produced by brown algae and bacteria.

Acyl derivatives are present in the fronds of the coastal woodfern, Dryopteris arguta or in Dryopteris crassirhizoma.
The anthelmintic activity of the root of Dryopteris filix-mas has been claimed to be due to flavaspidic acid, a phloroglucinol derivative.

Formylated phloroglucinol compounds (euglobals, macrocarpals and sideroxylonals) can be found in Eucalyptus species.
Hyperforin and adhyperforin are two phloroglucinols found in St John's wort.

Humulone is a phloroglucinol derivative with three isoprenoid 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 as Ecklonia stolonifera, Eisenia bicyclis or species in the genus Zonaria produce phloroglucinol and phloroglucinol derivatives.
Brown algae also produce a type of tannins known as phlorotannins.

The bacterium Pseudomonas fluorescens produces phloroglucinol, phloroglucinol carboxylic acid and diacetylphloroglucinol.

Reactions of Phloroglucinol:

Tautomerism and acid-base behavior:
Phloroglucinol is a weak triprotic acid.
The first two pKas are 8.5 and 8.9.
Phloroglucinol behaves as a mixture with the 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 Phloroglucinol behaves also like a benzenetriol as the three hydroxyl groups can be methylated to give 1,3,5-trimethoxybenzene.

For the neutral compound, the keto tautomers are undetectable spectroscopically.
Upon deprotonation, the keto tautomer predominates.

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.
Phloroglucinol does not boil intact, but it does sublime.

The Hoesch reaction allows the synthesis of 2,4,6-trihydroxyacetophenone (THAP) from phloroglucinol.

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).

Phloroglucinol readily forms 5-aminoresorcinol (aka phloramine) in aqueous ammonia at low temperatures.
Reaction of phloroglucinol and phloretic acid gives 30% yield of phloretin.

Stability and Reactivity of Phloroglucinol:

Chemical stability:
Phloroglucinol is generally stable under normal ambient temperatures and recommended storage conditions.

Reactivity:
Phloroglucinol may react with strong oxidizing agents and other highly reactive substances.

Conditions to avoid:
Avoid excessive heat, moisture, dust formation, and prolonged exposure to incompatible materials.

Incompatible materials:
Avoid strong oxidizing agents, strong bases, acid chlorides, and other highly reactive chemicals.

Hazardous decomposition products:
Thermal decomposition or combustion may generate carbon monoxide, carbon dioxide, and irritating organic fumes.

Handling and Storage of Phloroglucinol:

Safe handling:
Handle in a well-ventilated area and avoid generating or inhaling dust.
Prevent unnecessary contact with the skin and eyes and maintain good workplace hygiene.

Storage conditions:
Keep the container tightly closed in a cool, dry, and well-ventilated place.
Protect from moisture, excessive heat, and incompatible substances.

First Aid Measures of Phloroglucinol:

Inhalation:
Move the affected person to fresh air and keep them comfortable for breathing.
Seek medical attention if symptoms persist.

Skin contact:
Remove contaminated clothing and wash the affected skin thoroughly with soap and water.
Obtain medical advice if irritation develops.

Eye contact:
Rinse cautiously with plenty of water for several minutes.
Remove contact lenses if present and easy to do, continue rinsing, and seek medical attention if irritation persists.

Ingestion:
Rinse the mouth thoroughly with water.
Seek medical advice if discomfort or adverse symptoms occur.

Firefighting Measures of Phloroglucinol:

Suitable extinguishing media:
Use water spray, dry chemical, carbon dioxide, or suitable foam according to surrounding fire conditions.

Protective equipment:
Firefighters should wear appropriate protective clothing and self-contained breathing apparatus where necessary.

Fire-related decomposition:
Combustion may produce carbon monoxide, carbon dioxide, and irritating decomposition fumes.

Accidental Release Measures of Phloroglucinol:

Personal precautions:
Provide adequate ventilation and avoid creating airborne dust.
Wear suitable personal protective equipment during cleanup.

Cleanup methods:
Carefully sweep or collect spilled material without generating excessive dust.
Place the recovered material in a suitable closed container for disposal.

Environmental precautions:
Prevent unnecessary release into drains, waterways, and soil.

Exposure Controls/Personal Protective of Phloroglucinol:

Engineering controls:
Provide adequate general ventilation or local exhaust ventilation where dust may be generated.

Eye protection:
Wear suitable safety glasses or chemical protective goggles.

Hand protection:
Wear appropriate chemical-resistant protective gloves.

Skin protection:
Wear suitable laboratory or industrial protective clothing to minimize direct contact.

Respiratory protection:
Use suitable particulate respiratory protection when ventilation is insufficient or airborne dust levels are elevated.

Hygiene measures:
Wash hands thoroughly after handling.
Avoid eating, drinking, or smoking in areas where phloroglucinol is handled or stored.

Identifiers of Phloroglucinol:
CAS Number: 108-73-6
ChEBI: CHEBI:16204
ChEMBL: ChEMBL473159
ChemSpider: 352
ECHA InfoCard: 100.003.284
EC Number: 203-611-2
KEGG: D00152
C02183
PubChem CID: 359
RTECS number: UX1050000
UNII: DHD7FFG6YS
CompTox Dashboard (EPA): DTXSID9048354
InChI: InChI=1S/C6H6O3/c7-4-1-5(8)3-6(9)2-4/h1-3,7-9H
Key: QCDYQQDYXPDABM-UHFFFAOYSA-N
InChI: InChI=1/C6H6O3/c7-4-1-5(8)3-6(9)2-4/h1-3,7-9H
Key: QCDYQQDYXPDABM-UHFFFAOYAF
SMILES: c1c(cc(cc1O)O)O

Empirical Formula (Hill Notation): C6H6O3
CAS Number: 108-73-6
Molecular Weight: 126.11
UNSPSC Code: 12352100
NACRES: NA.22
PubChem Substance ID: 57652786
EC Number: 203-611-2
Beilstein/REAXYS Number: 1341907
MDL Number: MFCD00002286
Assay: ≥99.0% (HPLC)
Form: solid

Properties of Phloroglucinol:
Quality Segment: 200
Assay: ≥99.0% (HPLC)
Form: solid
Impurities: diresorcin, none detected, ≤2% water
Melting Point: 215-220 °C
SMILES String: Oc1cc(O)cc(O)c1
InChI: 1S/C6H6O3/c7-4-1-5(8)3-6(9)2-4/h1-3,7-9H
InChI Key: QCDYQQDYXPDABM-UHFFFAOYSA-N

Chemical Formula: C6H6O3
Molar Mass: 126.111 g·mol−1
Appearance: colorless to beige solid
Melting Point: 219 °C (426 °F; 492 K)
Solubility in Water: 1 g/100 mL
Solubility: soluble in diethyl ether, ethanol, pyridine
Acidity (pKa): 8.45
Magnetic Susceptibility (χ): −73.4×10−6 cm3/mol

Pharmacology of Phloroglucinol:
ATC code: A03AX12 (WHO)

Names of Phloroglucinol:

Preferred IUPAC name:
Benzene-1,3,5-triol

Other names:
phloroglucine
1,3,5-benzenetriol
1,3,5-trihydroxybenzene
cyclohexane-1,3,5-trione