Diethylpropion (90-84-6) Physical and Chemical Properties
Diethylpropion
A small-molecule sympathomimetic aromatic ketone historically used as an anorectic; typically sourced for formulation development, analytical reference standards and R&D under controlled procurement.
| CAS Number | 90-84-6 |
| Family | Sympathomimetic amines |
| Typical Form | Powder or crystalline solid |
| Common Grades | EP, JP, USP |
Diethylpropion is a tertiary-amine aromatic ketone belonging to the propiophenone structural class; systematically it is 2-(diethylamino)-1-phenylpropan-1-one. The molecule contains a phenyl ring conjugated to a carbonyl (propiophenone core) with a diethylamino substituent at the α-carbon. This arrangement produces a lipophilic aromatic-ketone scaffold with a single basic tertiary amine site that can be protonated to give a water-soluble ammonium salt (the clinically used hydrochloride). The relatively low topological polar surface area (\(20.3\)) and the absence of hydrogen-bond donors (H‑bond donor count \(0\)) promote membrane permeability for the neutral free base, while protonation markedly increases aqueous solubility and renal excretion for the salt form.
Electronically, the carbonyl is conjugated to the aromatic ring, so the ketone exhibits the usual susceptibility to nucleophilic reduction and can participate in enolization-like chemistry at the α-carbon; however, the presence of the diethylamino substituent alters steric and electronic properties relative to simple propiophenone. Acid–base behaviour is dominated by the tertiary amine: the compound has an estimated \(\mathrm{p}K_a\) in the basic range (near physiological pH), meaning the free base and its protonated form coexist depending on pH and formulation. Lipophilicity values place the free base in a moderately lipophilic class (logP ≈ 2.8), consistent with good oral absorption for the neutral species and efficient central nervous system penetration when unprotonated.
Pharmacologically, diethylpropion is an indirect sympathomimetic stimulant used as a short‑term anorectic; its clinical utility is based on stimulation of catecholamine release and downstream appetite suppression. The hydrochloride salt is the accepted pharmaceutical form used in immediate- and extended‑release oral tablets. Common commercial grades reported for this substance include: EP, JP, USP.
Basic Physicochemical Properties
Density and Solid-State Form
Physical description: Solid. The material is reported as white or creamy white small crystals or a crystalline powder in its common salt/formulated forms. The free base is typically isolated as a crystalline solid or oil depending on purification; the hydrochloride exists as crystalline salt forms that are hygroscopic.
Melting Point
Melting point: 168.
Crystalline hydrochloride material is reported to decompose at approximately \(168\,^\circ\mathrm{C}\) (dec.). If a single numeric melting point is required for a particular form (free base vs. hydrochloride), confirm the specific salt form because decomposition and melting behaviour differ between the free base and the salt.
Solubility and Dissolution Behavior
Aqueous solubility data are reported in two formats: a measured value of 1.22e+00 g/L and qualitative solubility statements for the hydrochloride form. For diethylpropion hydrochloride, typical solubility notes indicate "1 g sol in: about 0.6 mL water, about 0.6 mL chloroform, 1 mL absolute methanol, 1 mL alcohol; practically insoluble in ether." These data reflect that the protonated hydrochloride salt has substantially greater aqueous solubility than the free base. In practice, formulation selection (free base vs. hydrochloride; immediate vs. extended‑release) determines dissolution kinetics: salts and extended‑release matrices are used to control rate and extent of drug release for oral administration.
Chemical Properties
Acid–Base Behavior and Qualitative pKa
Diethylpropion is a tertiary amine; an estimated \(\mathrm{p}K_a\) of 8.2 is reported for the basic site. At physiological pH (\(\sim7.4\)) a significant fraction is protonated, and at lower pH (stomach) the protonated form predominates. Protonation increases aqueous solubility and reduces membrane permeability relative to the neutral free base; this pH‑dependent ionization underpins the use of hydrochloride salt forms for oral dosage forms and helps explain renal excretion behaviour and acid‑urine‑dependent elimination.
Reactivity and Stability
The compound is chemically stable under dry air; diethylpropion hydrochloride is described as stable in dry air but hygroscopic. The aromatic ketone functionality is chemically competent toward reduction (keto → alcohol) and N‑dealkylation is a major metabolic pathway in biological systems. Hydrolytic cleavage under neutral environmental conditions is not expected because the molecule lacks hydrolytically labile functional groups beyond the ketone (which does not rapidly hydrolyse under ambient aqueous conditions). Thermal decomposition of the hydrochloride salt releases very toxic fumes including hydrogen chloride and nitrogen oxides; appropriate thermal controls are required during processing and waste handling.
Molecular Parameters
Molecular Weight and Formula
Molecular formula: C13H19NO
Molecular weight: 205.30 \(\mathrm{g}\,\mathrm{mol}^{-1}\)
LogP and Structural Features
LogP (XLogP3‑AA): 2.8.
The calculated/topological descriptors indicate moderate lipophilicity (XLogP 2.8) combined with a low TPSA (\(20.3\)), zero H‑bond donors and two H‑bond acceptors. Structurally, the phenyl–carbonyl core contributes to lipophilicity and π‑conjugation, while the tertiary diethylamino substituent provides a single basic center. This balance of properties yields a molecule that is orally bioavailable as the free base (or salt) and able to cross lipid membranes, with protonation state strongly modulating aqueous solubility and distribution.
Structural Identifiers (SMILES, InChI)
SMILES: CCN(CC)C(C)C(=O)C1=CC=CC=C1
InChI: InChI=1S/C13H19NO/c1-4-14(5-2)11(3)13(15)12-9-7-6-8-10-12/h6-11H,4-5H2,1-3H3
InChIKey: XXEPPPIWZFICOJ-UHFFFAOYSA-N
Identifiers and Synonyms
Registry Numbers and Codes
CAS number: 90-84-6
EC number: 202-019-1
UNII: Q94YYU22B8
ChEBI: CHEBI:4530
ChEMBL: CHEMBL1194666
DEA code number (controlled substance): 1610 (Schedule IV)
DrugBank: DB00937
Synonyms and Brand-Independent Names
Common synonyms appearing in registry lists include: Diethylpropion; Amfepramone; 2‑Diethylaminopropiophenone; Amfepramon; Phepranon; 2‑(Diethylamino)-1-phenylpropan-1-one. Multiple historical and regional names (including several trade/brand names and alternate salt descriptors) exist for both the free base and hydrochloride salt; use the systematic IUPAC name 2-(diethylamino)-1-phenylpropan-1-one for unambiguous identification in manufacturing and quality documentation.
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
Diethylpropion is used pharmaceutically as a centrally acting appetite suppressant (an anorectic) for short‑term management of exogenous obesity as an adjunct to caloric restriction, exercise and behaviour modification. The hydrochloride salt is the marketed active pharmaceutical ingredient (API) in immediate‑ and extended‑release oral tablets. It is a controlled substance (Schedule IV) in jurisdictions that regulate sympathomimetic stimulants.
Formulation and Development Contexts
Typical pharmaceutical presentations include immediate‑release tablets (e.g., 25 mg) and controlled‑release/extended‑release tablets (e.g., 75 mg) of the hydrochloride. The hydrochloride salt is preferred for oral formulations due to enhanced aqueous solubility and handling properties; manufacture commonly involves formation of the free base followed by conversion to the hydrochloride salt. Extended‑release products use resin or matrix strategies to modulate release over 12 hours, whereas immediate‑release tablets deliver therapeutic levels for approximately 4 hours.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
In industrial and QC practice, diethylpropion is supplied and qualified as pharmaceutical API (pharmacopeial grades), analytical reference standards, or technical/industrial grades for research and nonclinical uses. Pharmacopoeial grades (EP, JP, USP) denote compliance with corresponding monograph requirements where available; analytical standards are used for assay, impurity profiling and stability testing.
General Quality Attributes (Qualitative Description)
Key quality attributes for the API and formulated products include identity (spectroscopic and chromatographic confirmation), assay (potency of active free base expressed as diethylpropion or as the hydrochloride salt), residual solvents, water content (the hydrochloride is hygroscopic), polymorphic form/crystallinity, and impurity profile including degradants and related substances (e.g., N‑dealkylation products, oxidation/reduction impurities). Stability specifications address moisture sensitivity for the hydrochloride salt and thermal decomposition risks for processing.
Common commercial grades reported for this substance include: EP, JP, USP.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
Diethylpropion is a centrally acting sympathomimetic stimulant with risks and toxicology characteristic of amphetamine‑class agents. Acute and chronic adverse effects include central nervous system stimulation (restlessness, agitation, insomnia, tremor, seizures), cardiovascular effects (tachycardia, hypertension, arrhythmias, potential myocardial ischemia), psychiatric disturbances (agitation, psychosis with chronic abuse), and other systemic effects (hyperthermia, rhabdomyolysis, renal complications). Reported acute oral LD50 values include \(600\,\mathrm{mg}\,\mathrm{kg}^{-1}\) (mouse), \(50\,\mathrm{mg}\,\mathrm{kg}^{-1}\) (rat), and \(225\,\mathrm{mg}\,\mathrm{kg}^{-1}\) (dog). The compound and its metabolites are excreted primarily via the kidney; half‑life values for active aminoketone metabolites are reported in the range of 4–6 hours, with the duration of action depending on formulation (immediate‑release ≈ 4 hours; extended‑release ≈ 12 hours).
Contraindications and precautions include preexisting cardiovascular disease, severe hypertension, hyperthyroidism, glaucoma, history of drug abuse, and concurrent or recent monoamine oxidase inhibitor therapy (concurrent use contraindicated). Diethylpropion and its metabolites distribute into breast milk and cross the placenta; use in pregnancy and lactation requires caution.
Storage and Handling Guidelines
Diethylpropion hydrochloride is hygroscopic and should be protected from moisture. Commercial tablets and bulk salt should be stored in tight containers at controlled ambient temperatures, preferably below \(30\,^\circ\mathrm{C}\). The free base and process intermediates should be handled to avoid inhalation and dermal exposure; engineering controls (local exhaust, closed transfer systems), appropriate PPE (gloves, eye protection, lab coat) and dust suppression are recommended in manufacturing and QC environments. Thermal processing should avoid temperatures that cause decomposition; decomposition of the hydrochloride emits hydrogen chloride and nitrogen oxides, so thermal treatment should be performed with suitable fume control.
For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and applicable local legislation.
