Phloroglucinol

Product Overview

Phloroglucinol (also known as 1,3,5-trihydroxybenzene or phloroglucin) is a phenolic compound of extremely simple structure — three hydroxyl groups symmetrically attached at the 1, 3 and 5 positions of a benzene ring. This symmetrical triphenolic structure gives it strong reducing power and metal-complexing ability (e.g., forming a dark complex with Fe³⁺), which is why it is used in analytical chemistry as a reagent for detecting pentoses, lignin, gastric hydrochloric acid and more.

What makes its pharmacological class unique: It is a musculotropic, non-atropine, non-papaverine pure smooth muscle antispasmodic — these three “non”s are the key to how it differs from other antispasmodics:

• Non-atropine: It does not act on cholinergic receptors and has no anticholinergic action, so it produces no anticholinergic adverse effects such as dry mouth, blurred vision, dysuria or tachycardia. This is precisely why it can be used in populations where anticholinergics should be used with caution, such as elderly men (prostatic hyperplasia) and glaucoma patients.
• Non-papaverine: It is not an opium alkaloid and has no addictive potential or related central effects.
• Selective antispasmodic: It acts only on spastic (pathologically contracted) smooth muscle and has minimal effect on normal physiological contractions, so it causes little interference with normal physiological functions such as gastrointestinal motility.

Safety profile: It does not cause hypotension, tachycardia or arrhythmia, has minimal effect on cardiovascular function, and is suitable for patients of all ages. The half-life is approximately 15 minutes; plasma concentration falls rapidly within 4 hours of administration, then declines slowly.

Clinical value of “no anticholinergic side effects”: This characteristic gives it an advantage in the emergency management of spasmodic pain — it provides rapid spasmolysis and analgesia while avoiding the common adverse effects and contraindication restrictions of anticholinergic drugs.

Technical Specifications

• Standards: CHP / USP / EP

• Specification: 0.99 (purity ≥99.0%, HPLC); reagent grade commonly ≥98% (anhydrous), ≥99% (dihydrate)

• CAS No.: 108-73-6 (anhydrous / anhydrous phloroglucinol; EINECS 203-611-2, MDL MFCD00002286, RTECS SY1050000, Beilstein 1341907, Merck Index 14,7328)

  • Dihydrate (the common form of API for injection): CAS 6099-90-7, molecular formula C₆H₆O₃·2H₂O (also written C₆H₁₀O₅), molecular weight 162.14
  • The chemical name of the marketed injection in China (Phloroglucinol for Injection) is “1,3,5-trihydroxybenzene dihydrate”, molecular formula C₆H₆O₃·2H₂O
  • The two forms have different molecular weights (126.11 vs 162.14); the form must be clearly specified for assay and formulation conversions

• Molecular formula: C₆H₆O₃

• Molecular weight: 126.11 (consistent across Thermo Fisher, Viva Supply, iChemistry and popular science sources); calculated value 126.110; exact mass 126.032

• Appearance: White to pale yellow (white to light cream) crystals or crystalline powder; darkens on exposure to light; sweet taste; the dihydrate is a colorless or white / pale yellow crystal or crystalline powder and is hygroscopic

• Purity (HPLC): ≥ 99.0%

• Melting point: 215–220 °C (Thermo Fisher records “clear melt 213–223 °C”; Viva Supply records 215–220 °C; consistent across iChemistry, popular science sources and the Wujing database — recommended). A single value of 218 °C is also recorded (popular science article text, iChemistry property description). The dihydrate (6099-90-7) melting point is recorded as 218–221 °C — because the dihydrate dehydrates to the anhydrous form at about 110 °C, the measured value is in practice mostly the melting of the anhydrous form, hence the close values. One source gives 131–133 °C for the dihydrate, nearly 90 °C below the mainstream value; judged to be a data entry or source error and not adopted

• Specific rotation: Not applicable — the molecule is highly symmetrical (1,3,5-substituted), has no chiral centers and no E/Z isomerism

• Chemical name: 1,3,5-trihydroxybenzene; benzene-1,3,5-triol; English IUPAC: benzene-1,3,5-triol

• Stereochemistry: No stereocenters; 5 keto–enol tautomers exist

• Solubility: Soluble in 100 parts water, 10 parts ethanol, 0.5 parts pyridine; soluble in diethyl ether; water solubility approx. 11.17 g/L (room temperature, Viva Supply); slightly soluble in water (the dihydrate is recorded as slightly soluble). Freely soluble in ethanol, diethyl ether, benzene and pyridine; insoluble in chloroform

• Computed physicochemical parameters: Density approx. 0.801 g/mL (20 °C); bulk density approx. 560 kg/m³; boiling point approx. 331.1 °C (760 mmHg; another estimated value 194.21 °C); flash point approx. 14 °C (anhydrous, listed in the hazardous chemicals catalogue) / 100 °C (dihydrate); refractive index n²⁰/D approx. 1.365; vapor pressure approx. 8.27×10⁻⁵ mmHg (25 °C); LogP approx. 0.80 (octanol/water partition coefficient log value recorded as −0.19; the dihydrate recorded as 0.675); H-bond donors 3 / acceptors 3; topological polar surface area approx. 60.69 Ų

• Chemical property notes: Strongly reducing and readily oxidized by oxidizing agents to quinone compounds; incompatible with acid chlorides, acid anhydrides, alkalis and oxidizing agents; decomposes at high temperature; light-sensitive — must be stored protected from light

• Marketed dosage form: Phloroglucinol for Injection 40 mg/vial (expressed as the dihydrate); excipient: mannitol; dissolve completely in an appropriate volume of water for injection immediately before use

• Storage: Protect from light, store sealed in a cool, dry place; keep separate from oxidizing agents; warehouse ventilated, cool and dry; the dihydrate may be stored at room temperature — keep dry and protected from moisture

Applications

• Acute spasmodic pain caused by digestive and biliary dysfunction (core indication): For acute spasmodic pain caused by dysfunction of hollow viscera such as the gastrointestinal and biliary tracts, e.g., gastrointestinal spasm and biliary colic

• Acute spasmodic urethral, bladder and renal colic: For spasmodic pain of the urinary system, including renal colic, ureteral spasm and bladder spasmodic pain

• Gynecological spasmodic pain: For spasmodic pain in gynecology (clinical literature reports its use in promoting labor progress, threatened miscarriage, primary dysmenorrhea, hysteroscopy, induced abortion, IUD removal after menopause, embryo transfer, hyperemesis gravidarum, hypertensive disorders of pregnancy, renal colic in pregnancy, postpartum urinary retention, premature rupture of membranes and postpartum uterine contraction pain) — specific indications are subject to the latest labeling in each jurisdiction

• Dosage and administration (marketed injection in China): Intramuscular or intravenous injection: 1–2 vials (40–80 mg) per dose, 1–3 vials (40–120 mg) daily; intravenous infusion: the daily dose may reach 5 vials (200 mg), diluted in 5% or 10% glucose injection for intravenous infusion. Onset in about 5–10 minutes; half-life approximately 15 minutes

• Pharmacological advantages: Acts only on spastic smooth muscle with minimal effect on normal smooth muscle; no anticholinergic action; does not cause hypotension, tachycardia or arrhythmia; minimal effect on cardiovascular function; does not affect bile secretion; short half-life (approx. 15 minutes); suitable for patients of all ages with good compliance for long-term or high-dose use

• Analytical chemistry and other industrial uses: Used for the detection of antimony, arsenic, cerium, chromates, chromium, gold, iron, mercury, nitrite, osmium, palladium, tin, vanadium, vanillin and lignin; for the determination of furfural, pentoses, pentosans, methanol, chloral hydrate, turpentine, lignified cell tissue and hydrochloric acid in gastric juice; decalcification of bone specimens; the active component of Tollens’ reagent and Günzburg’s reagent; depolymerization studies of condensed tannins; used as a coupling agent in printing; used in the synthesis of 2,4,6-triamino-1,3,5-trinitrobenzene, trinitrophloroglucinol and pharmaceuticals (e.g., flopropione)

• Formulation and manufacturing: For formulation development of lyophilized powder for injection (40 mg/vial, excipient mannitol); the API readily discolors on exposure to light and is reducing in nature, so production must focus on controlling light protection, oxidation prevention and related substances (especially the oxidation product quinones), moisture (dihydrate water of crystallization) and assay; suitable for analytical method development and validation, stability studies, impurity reference standards, and GMP scale-up with CMO / CDMO contract manufacturing

Safety notice: This product is an active pharmaceutical ingredient (API) intended solely for compliant industrial, research and pharmaceutical manufacturing use; it is not for end clinical use or guidance for self-administration. The finished product is a prescription drug and must be prescribed by a physician. Adverse reactions: Allergic reactions such as rash and urticaria occur very rarely. Important incompatibility: The injection must not be mixed with metamizole (analgin) in the same syringe (may cause thrombophlebitis). Pregnancy and special populations: Because of its short half-life (approx. 15 minutes) and the rapid decline in plasma concentration within 4 hours of administration, the literature considers it relatively safe for pregnant women and the fetus, but it must still be used after a physician’s benefit–risk assessment. The API’s GHS classification is Skin Irritation Category 2, Serious Eye Irritation Category 2 and Specific Target Organ Toxicity (single exposure, respiratory irritation) Category 3 (H315 / H319 / H335); hazard symbol Xi (irritant); risk phrases R36/37/38 (irritating to eyes, respiratory system and skin). The anhydrous form has a flash point of approximately 14 °C and is listed under Item 2828 of the Catalogue of Hazardous Chemicals (2015 edition); distribution and procurement require the corresponding qualifications; rat oral LD50 approx. 5200 mg/kg. Wear protective gloves, protective clothing, and respiratory, eye and face protection during handling; avoid dust inhalation and contact with skin and eyes; store protected from light, separate from oxidizing agents, acid chlorides, acid anhydrides and alkalis.

Product information: please contact us. This information is for reference only.