Chlorphenesin Carbamate (886-74-8) Physical and Chemical Properties
Chlorphenesin Carbamate
A small‑molecule carbamate ester (chlorophenoxy derivative) typically supplied as a white to off‑white powder for use in pharmaceutical formulation, analytical testing and R&D.
| CAS Number | 886-74-8 |
| Family | Carbamate esters |
| Typical Form | White to off-white powder or crystals |
| Common Grades | BP, EP, JP |
Chlorphenesin carbamate is an O‑carbamate derivative of a chlorinated phenoxy‑substituted glycerol backbone; the molecular formula is \(\ce{C10H12ClNO4}\). Structurally it is classified as a carbamate ester and a monochlorobenzene derivative, containing a p‑chlorophenoxy moiety linked through an ether to a 2‑hydroxypropyl chain that is further functionalized as a carbamate. The molecule presents a single undefined stereocenter at the glycerol‑derived carbon and combines a moderately polar carbamate/secondary alcohol region with a lipophilic aryl ether, giving mixed amphiphilic character.
Electronically the compound has no formal charge at physiological pH and presents two hydrogen‑bond donors and four hydrogen‑bond acceptors (donor/acceptor counts: 2/4), consistent with appreciable aqueous hydrogen‑bonding but limited intrinsic ionization. Topological polar surface area (TPSA = 81.8 Å2) and an XLogP3 of 1.2 indicate moderate polarity and moderate lipophilicity, compatible with oral absorption but limited passive brain penetration relative to highly lipophilic agents. The carbamate functionality is susceptible to hydrolytic cleavage under strong acidic or basic conditions and to enzymatic carbamate hydrolysis in biological systems; the aryl ether (p‑chlorophenoxy) unit is relatively resistant to simple hydrolysis but can be biotransformed oxidatively to chlorophenolic/acid metabolites under metabolic conditions.
Chlorphenesin carbamate has been used as a centrally acting skeletal muscle relaxant in human and veterinary medicine; it has also been described in contexts as a preservative-related derivative and has recorded use in oral tablet formulations and veterinary adjunctive therapy. Manufacturing typically proceeds by nucleophilic attack of p‑chlorophenol on glycidol followed by carbamoylation of the primary hydroxyl. Common commercial grades reported for this substance include: BP, EP, JP.
Basic Physicochemical Properties
Density and Solid-State Form
No experimentally established value for this property is available in the current data context.
Solid‑state and morphological descriptions: reported forms include "CRYSTALS FROM BENZENE + TOLUENE" and "WHITE TO OFF‑WHITE POWDER". The material is described as odorless and practically tasteless in organoleptic terms.
Melting Point
Melting point (experimental): 89–91 °C.
The observed melting range is consistent with a crystalline carbamate ester containing both hydrogen‑bonding functionality and a rigid aryl ether substituent; narrow melting ranges are useful for QC identification of crystalline batches.
Solubility and Dissolution Behavior
Reported qualitative solubility data: - "READILY SOL IN 95% ETHANOL, ACETONE, ETHYL ACETATE; FAIRLY READILY SOL IN DIOXANE; ALMOST INSOL IN COLD WATER, BENZENE, CYCLOHEXANE" - "SLIGHTLY SOL IN CHLOROFORM" - "FREELY SOL IN ALCOHOL"
Practical implications: the compound is readily soluble in polar aprotic and moderately polar protic organic solvents (ethanol, acetone, ethyl acetate) but shows very limited solubility in nonpolar hydrocarbons and cold water. Formulation strategies for oral solid dosage forms therefore rely on fine particle size, solvent selection for granulation/spray drying, or solubilizing excipients (cosolvents, surfactants) to achieve acceptable dissolution rates.
Chemical Properties
Acid–Base Behavior and Qualitative pKa
No experimentally established value for this property is available in the current data context.
Qualitative acid–base description: the molecule lacks strongly ionizable acidic or basic functional groups under normal \(\mathrm{pH}\) ranges; the carbamate NH is weakly acidic relative to aliphatic amines and is not expected to be substantially ionized at physiological \(\mathrm{pH}\). Consequently, aqueous ionization plays a minor role in solubility and permeability compared with hydrogen bonding and lipophilicity.
Reactivity and Stability
Stability: described as "STABLE IN LIGHT, AIR, AND AT ORDINARY TEMP." Carbamate esters are chemically susceptible to hydrolysis under prolonged exposure to strong acid or base and to enzymatic cleavage (esterases/carbamate hydrolases) in biological matrices; reported metabolic data confirm cleavage pathways that produce chlorophenolic metabolites and corresponding conjugates. The p‑chlorophenoxy ether is chemically robust to simple hydrolysis but can undergo oxidative metabolism to yield p‑chlorophenol, p‑chlorophenoxyacetic and p‑chlorophenoxy lactic acid derivatives under in vivo conditions. Oxidative degradation under aggressive oxidizing conditions may dechlorinate or oxidize the aryl moiety; accordingly, formulations and storage should avoid strong oxidants and extreme pH.
Molecular Parameters
Molecular Weight and Formula
Molecular weight (computed): 245.66 g·mol−1.
Molecular formula: \(\ce{C10H12ClNO4}\).
Exact/monoisotopic mass: 245.0454856.
Heavy atom count: 16. Formal charge: 0.
LogP and Structural Features
Calculated lipophilicity (XLogP3‑AA): 1.2.
Interpretation: the low‑to‑moderate XLogP is consistent with mixed polar (carbamate, secondary alcohol) and nonpolar (p‑chlorophenyl ether) domains and supports reasonable oral absorption with moderate distribution into tissues. Hydrogen‑bond donor count = 2; hydrogen‑bond acceptor count = 4; rotatable bond count = 6; TPSA = 81.8. These descriptors predict moderate aqueous solubility in protic solvents and the potential for multiple hydrogen‑bond interactions in binding or in solid‑state packing.
Structural Identifiers (SMILES, InChI)
SMILES: C1=CC(=CC=C1OCC(COC(=O)N)O)Cl
InChI: InChI=1S/C10H12ClNO4/c11-7-1-3-9(4-2-7)15-5-8(13)6-16-10(12)14/h1-4,8,13H,5-6H2,(H2,12,14)
InChIKey: SKPLBLUECSEIFO-UHFFFAOYSA-N
These canonical identifiers are suitable for informatics indexing, structure searches, and mass balance tracking in synthetic development.
Identifiers and Synonyms
Registry Numbers and Codes
CAS number: 886-74-8.
Additional registry identifiers (as reported): EC number 212-954-7; UNII codes 57U5YI11WP, HQC4WI89YG, G014XC07GH; ChEBI: CHEBI:3643; ChEMBL: CHEMBL607710; DrugBank: DB14656; KEGG: C07930 / D00770; NSC Number: 82943.
Synonyms and Brand-Independent Names
Selected synonyms and nonproprietary names reported include: - chlorphenesin carbamate - Maolate - Rinlaxer - [3-(4-chlorophenoxy)-2-hydroxypropyl] carbamate - 3-(p-Chlorophenoxy)-1,2-propanediol 1‑carbamate - U‑19,646 - NSC‑82943 - Carbamic acid 3-(p‑chlorophenoxy)-2‑hydroxypropyl ester
(Several additional deposited synonyms and historical names exist for regulatory and legacy indexing.)
Industrial and Pharmaceutical Applications
Role as Active Ingredient or Intermediate
Therapeutic role: used as a centrally acting skeletal muscle relaxant for symptomatic relief of painful muscle spasm arising from trauma, inflammation, intervertebral disc syndrome, osteoarthritis, and rheumatoid arthritis. It has seen human and veterinary use as an adjunctive agent; adverse pharmacodynamic effects commonly include sedation and impairment of alertness typical of centrally acting muscle relaxants.
Manufacturing role: synthesized by addition of p‑chlorophenol to glycidol (2,3‑epoxy‑1‑propanol) followed by carbamoylation of the primary hydroxy group with carbamoyl chloride or related reagents; the route accommodates stereochemical outcomes and is amenable to scale‑up under conventional organic process conditions.
Formulation and Development Contexts
Formulation considerations derive from solubility and stability: free solubility in alcohols and polar organic solvents facilitates preparation of alcoholic solutions and some liquid formulations, while poor cold water solubility requires particle size reduction, solubilizers, or co‑solvent approaches for aqueous dosage forms. The crystalline melting range (89–91 °C) and stable behavior at ordinary storage temperatures support typical solid oral dosage manufacturing and storage. Because metabolism produces chlorophenolic derivatives, impurity profiling and control of oxidative degradation products are relevant in QC and stability testing.
If a concise application summary is required beyond the above, in practice this substance is selected based on its pharmacological class and the general properties described.
Specifications and Grades
Typical Grade Types (Pharmaceutical, Analytical, Technical)
Typical commercial grade concepts applicable to this substance include pharmaceutical (compendial), analytical, and technical grades. Specific compendial grades reported include BP, EP, JP; these denote availability of material intended to meet monograph quality or regulatory standards in different pharmacopeial jurisdictions.
General Quality Attributes (Qualitative Description)
Quality attributes of interest for specification include: - Appearance (e.g., crystalline white to off‑white powder) - Purity by HPLC or GC - Residual solvents (given solubility in organic solvents used during manufacture) - Assay of active carbamate content - Stereochemical composition (presence of undefined stereocenter/ratio) - Related substances such as p‑chlorophenol or oxidized derivatives
No specific assay limits or impurity thresholds are provided here; typical industry practice is to define those parameters according to the intended grade (pharmaceutical vs. technical) and regulatory requirements.
Safety and Handling Overview
Toxicological Profile and Exposure Considerations
Human adverse effects reported: drowsiness, dizziness, GI disturbances (epigastric distress, nausea), CNS effects consistent with centrally acting muscle relaxants (sedation, ataxia, blurred vision), and rare hypersensitivity reactions (rash, pruritus, anaphylactoid events, leukopenia). Warning: persons taking the drug should not drive or operate machinery due to impaired alertness.
Animal toxicity data: oral LD50 values reported in rats ≈ 744 and 817 mg·kg−1 (male and female, respectively) and in mice ≈ 807 and 844 mg·kg−1 (male and female, respectively). Repeated high‑dose administration in rodents produced effects on liver and adrenal glands and inhibited body‑weight gain at elevated doses. Metabolism yields glucuronide conjugates and p‑chlorophenoxy acid/sulfate derivatives; hepatic processing is a primary elimination pathway, and liver function may be adversely affected with use.
Exposure control: typical PPE for powders and organic solvent work should be used (gloves, eye protection); avoid inhalation of dust. Because the compound is sedating, occupational exposure leading to systemic uptake should be minimized.
Storage and Handling Guidelines
Stability statement: stable in light, air, and at ordinary temperature. Recommended general practices: store in a cool, well‑ventilated area in tightly closed containers away from strong acids, bases, and oxidizing agents; avoid prolonged exposure to extremes of pH and strong oxidants which can promote hydrolysis or oxidative degradation. For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
