Fenoterol (13392-18-2) Physical and Chemical Properties
Fenoterol
A resorcinol-class, short-acting beta-2 adrenergic agonist small molecule commonly managed as the free base or hydrobromide salt for pharmaceutical formulation, analytical development and API sourcing.
| CAS Number | 13392-18-2 |
| Family | Resorcinol-class beta-2 agonists |
| Typical Form | Powder or crystalline solid |
| Common Grades | BP, EP, JP |
Fenoterol is a synthetic small-molecule beta-2 adrenergic agonist belonging to the resorcinol class of phenolic sympathomimetics. Structurally it comprises two substituted phenyl rings (a resorcinol motif and a para-hydroxyphenyl group) linked through a short aliphatic chain that carries a secondary amino group and a secondary alcohol. The combination of multiple phenolic hydroxyls, a secondary alcohol and a tertiary (benzylic) substitution pattern on the alkylamine confers both hydrogen-bonding capacity and a degree of steric hindrance around the basic nitrogen, characteristics that govern receptor affinity, salt formation and metabolic routes.
Electronically, the molecule contains several polar functionalities (phenolic OH groups, a secondary alcohol and a secondary amine) that increase topological polar surface area and hydrogen-bond donor/acceptor counts; these attributes reduce passive membrane permeability relative to purely lipophilic analogues but still allow sufficient lipophilicity for receptor access (computed XLogP3-AA = 2). The free base exhibits low aqueous solubility, while protonation of the basic amine enables preparation of crystalline, more water-soluble salts (commonly the hydrobromide). Phenolic groups are mildly acidic and are susceptible to oxidative transformations under strong oxidizing conditions; the secondary amine is a site for protonation and for hepatic N-dealkylation in metabolic clearance.
Pharmacologically, fenoterol functions as a selective beta-2 adrenergic receptor agonist used as a bronchodilator and, historically, as a tocolytic; in pharmaceutical practice the hydrobromide salt has been the predominant dosing form to maximize aqueous solubility and formulation stability. Common commercial grades reported for this substance include: BP, EP, JP.
Basic Physicochemical Properties
Density and Solid-State Form
Physical description: Solid.
No experimentally established value for this property is available in the current data context.
Melting Point
Melting point (free base): 222-223 \(\,^\circ\mathrm{C}\).
Solubility and Dissolution Behavior
Aqueous solubility (free base, experimental): 1.62e-01 \(\mathrm{g}\,\mathrm{L}^{-1}\).
Qualitative dissolution behaviour: the free base form of fenoterol has very limited water solubility (value above). Protonation of the secondary amine to form hydrobromide or hydrochloride salts substantially increases aqueous solubility and is the standard approach used in pharmaceutical formulations to improve dissolution rate and bioavailability. The multiple phenolic hydroxyl groups support hydrogen-bonding interactions with solvents and excipients but do not compensate fully for the overall low aqueous solubility of the neutral base.
Chemical Properties
Acid–Base Behavior and Qualitative pKa
No experimentally established value for this property is available in the current data context.
Reactivity and Stability
Fenoterol contains two electron-rich phenolic (resorcinol-type) hydroxyl groups and a secondary alcohol; these functionalities are susceptible to oxidation under harsh oxidative or photochemical conditions, which can lead to discoloration and decomposition products. The secondary amine is readily protonated under acidic conditions, enabling stable crystalline salts; in biological systems the amine is a principal site for hepatic metabolism (N-dealkylation and conjugation pathways). Under neutral aqueous conditions the free base is chemically stable on laboratory timescales, but storage conditions that limit exposure to air, light and moisture are advised to minimize oxidative degradation and preserve assay purity.
Molecular Parameters
Molecular Weight and Formula
Molecular formula: \(\ce{C17H21NO4}\)
Molecular weight (computed): 303.35 \(\mathrm{g}\,\mathrm{mol}^{-1}\)
Exact/monoisotopic mass: 303.14705815
LogP and Structural Features
Computed XLogP3-AA: 2 (unitless).
Key computed descriptors:
- Hydrogen bond donor count: 5
- Hydrogen bond acceptor count: 5
- Topological polar surface area (TPSA): 93
- Rotatable bond count: 6
Interpretation: the presence of multiple hydroxyl groups and a secondary amine yields a moderately high polar surface area and a high number of hydrogen-bond donors/acceptors, consistent with reduced passive permeability relative to simpler phenethylamines. The computed XLogP value of 2 indicates moderate lipophilicity compatible with both aqueous and lipophilic environments; this balance supports receptor binding while the basic center enables formation of pharmaceutical salts to overcome the poor aqueous solubility of the free base.
Structural Identifiers (SMILES, InChI)
SMILES: CC(CC1=CC=C(C=C1)O)NCC(C2=CC(=CC(=C2)O)O)O
InChI: InChI=1S/C17H21NO4/c1-11(6-12-2-4-14(19)5-3-12)18-10-17(22)13-7-15(20)9-16(21)8-13/h2-5,7-9,11,17-22H,6,10H2,1H3
InChIKey: LSLYOANBFKQKPT-UHFFFAOYSA-N
Identifiers and Synonyms
Registry Numbers and Codes
- CAS Registry Number (free base): 13392-18-2
- Related CAS (hydrobromide salt): 1944-12-3
- Deprecated CAS listed: 20452-25-9
- EC number: 680-817-2
- ChEBI: CHEBI:149226
- ChEMBL: CHEMBL32800
- DrugBank: DB01288
- InChIKey: LSLYOANBFKQKPT-UHFFFAOYSA-N
Synonyms and Brand-Independent Names
Selected synonyms and nonproprietary names appearing in supplier and regulatory listings:
- Fenoterol
- Phenoterol
- p-Hydroxyphenylorciprenaline
- 5-[1-hydroxy-2-[1-(4-hydroxyphenyl)propan-2-ylamino]ethyl]benzene-1,3-diol (IUPAC)
- Fenoterolum (INN-Latin)
Note: multiple salt forms (e.g., hydrobromide, hydrochloride) and trade formulations have been used historically; the active free base and its salts may be listed under variant names.
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
Fenoterol is a selective beta-2 adrenergic receptor agonist used as an active pharmaceutical ingredient (API) for bronchodilation and, historically, as a tocolytic agent. Pharmaceutical formulations employ the hydrobromide salt to deliver the active moiety in inhalation and systemic preparations. The compound is pharmacologically active at beta-2 receptors, increasing intracellular cAMP in bronchial smooth muscle to produce bronchodilation.
Formulation and Development Contexts
Formulation strategies center on conversion of the free base to crystalline salts (commonly hydrobromide) to enhance aqueous solubility and processability. Both inhalation and systemic (parenteral or oral salt) delivery routes have been used; one practical note from clinical data is that absorption is reported to be unaffected by food. Hepatic metabolism is the primary clearance route, which is an important consideration in formulation and dose-finding studies. Use of antioxidant excipients and light‑/oxygen‑protective packaging can mitigate oxidative degradation during storage.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
Typical commercial grade concepts applicable to fenoterol:
- Pharmaceutical (pharmacopeial) grade for API manufacture and clinical use.
- Analytical grade for reference standards and impurity profiling.
- Technical grade for research and development or nonclinical purposes.
Commercial grades reported for this substance include: BP, EP, JP.
General Quality Attributes (Qualitative Description)
Quality attributes relevant for specification and release include: identity (structural confirmation by MS/IR/NMR), assay/potency, residual solvent profile, impurity and degradation product limits, moisture content, crystalline form (polymorphism), and purity related to salt form (free base vs specified salt). For pharmaceutical use, control of oxidative impurities (stemming from phenolic oxidation) and confirmation of stereochemical/positional isomer content are typical quality concerns.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
Fenoterol is pharmacologically active as a beta-2 adrenergic agonist; occupational exposure should be minimized to avoid unintended systemic exposure. Classified hazard information includes the following hazard statements as applied by suppliers/registrants: H302 — Harmful if swallowed; H332 — Harmful if inhaled. Signal word: Warning. The compound has been assigned acute toxicity categories in supplier classifications consistent with these statements.
Precautionary codes reported include: P261, P264, P270, P271, P301+P317, P304+P340, P317, P330, and P501, which reflect control of inhalation, ingestion and contamination, and management of exposure.
Storage and Handling Guidelines
Handle fenoterol in well-ventilated areas with appropriate personal protective equipment (gloves, eye protection, protective clothing) and engineering controls to prevent inhalation or dust generation. Avoid ingestion and minimize skin contact. Store in a cool, dry, well‑closed container protected from light and oxidizing conditions; antioxidant-containing packaging or inert atmosphere storage may be used where long-term stability is required. For detailed hazard, transport and regulatory information, users should refer to the product-specific Safety Data Sheet (SDS) and local legislation.
