Benzethonium Chloride (23-11-9) Physical and Chemical Properties
Benzethonium Chloride
A synthetic quaternary ammonium chloride supplied as a hygroscopic white crystalline solid, used as a cationic surfactant and antimicrobial ingredient in formulation and industrial hygiene applications.
| CAS Number | 23-11-9 |
| Family | Quaternary ammonium salts |
| Typical Form | Powder or crystalline solid |
| Common Grades | BP, EP, JP, USP |
Benzethonium chloride is a synthetic quaternary ammonium salt in the aromatic-ether class; structurally it is a benzyldimethylammonium cation substituted by a long, branched alkyl-phenoxy-ethoxyethyl chain, paired with chloride as the counter-ion. The molecule combines a permanently charged tertiary (quaternized) nitrogen center with a bulky hydrophobic aryl–alkyl segment and two ether linkages, producing an amphiphilic cationic surfactant that adsorbs strongly to negatively charged surfaces and biological membranes.
Electronically, the quaternary nitrogen carries a formal positive charge that is delocalized only to the extent allowed by proximal substituents (no classical resonance into the aromatic ring), while the chloride counter-ion remains ionically associated in solution or in the solid state. The ether oxygens provide modest hydrogen-bond acceptor capacity (three acceptors counted computationally) but no hydrogen-bond donors. Together these features yield a compound that is water soluble as an ion pair yet sufficiently lipophilic to partition into lipid interfaces and microbial membranes, giving rise to broad-spectrum biocidal activity.
Acid–base behaviour is defined by the permanently charged ammonium center (no acid–base dissociation in the usual \(\mathrm{p}K_a\) sense); solution pH is a formulation property rather than an intrinsic ionization equilibria. The compound shows marked surfactant-type behaviour (foam formation in aqueous media) and is classically incompatible with anionic detergents and soaps due to ion-pairing and precipitation. It is relatively stable under neutral conditions; strong oxidants, strong acids at high concentration, prolonged heat or light exposure, and certain nucleophiles can induce degradation. Common commercial grades reported for this substance include: BP, EP, JP, USP.
Basic Physical Properties
Physical form: colorless to white hygroscopic solid, typically presented as odorless white crystals or powder with a very bitter taste. The compound is described as mildly odorous in some preparations.
Melting point (reported values): 327 to 331 °F; 160–166 °C (reported ranges include 160–165 °C and 164–166 °C).
Solubility: reported aqueous solubility ranges from about 10 to 50 mg·mL^-1 at 64 °F; described broadly as “very soluble in water,” with solubility in alcohol, acetone and chloroform; slight solubility in ether. In aqueous solutions it commonly produces a foamy, soapy appearance due to surfactant behaviour.
pH of aqueous solution: a 1% aqueous solution has been reported with differing observations; some reports state a slightly alkaline litmus response, while others report a \(\mathrm{pH}\) between 4.8 and 5.5 for a 1% solution. These differences reflect formulation and counter-ion/impurity effects.
Refractive index (reported): values include 1.5101 @ 25 °C (D) and other reported optical indices such as 1.560 (alpha), 1.565 (beta), 1.589 (gamma).
Collision cross section: 210.3 \(\text{Å}^2\) for the [M+H]+ ion (TW method, calibrated).
Other physical notes: splintering slightly at 120 °C; hygroscopic and may be sensitive to prolonged exposure to air.
Solubility and Hydration
Benzethonium chloride is a water-soluble quaternary ammonium salt that readily forms micellar/adsorbed phases in aqueous media; solubility is sufficient to allow common antiseptic and preservative formulations (percent-level solutions). It is soluble in polar organic solvents such as alcohol and acetone, and shows only limited solubility in nonpolar solvents (ether). The substance may form monohydrate forms under certain conditions (monohydrate reported among historical synonyms), and concentrated aqueous or acidic environments can induce phase separation or precipitation of an oily phase that crystallizes on drying.
Thermal Stability and Decomposition
The quaternary ammonium structure and aryl–ether linkages confer moderate thermal stability under normal handling; reported stability for short periods (e.g., two weeks) at elevated temperatures (up to about \(140\,^\circ\mathrm{F}\)) has been noted. On further heating to decomposition the material emits irritating and toxic gases, including hydrogen chloride and nitrogen oxides (generically \(HCl\) and \(NO_x\)). The compound is combustible and produces irritating or toxic fumes on burning; fire response should therefore allow for acid gas and nitrogen oxide exposure.
Chemical Properties
Complex Formation and Coordination
As a quaternary ammonium salt, benzethonium chloride does not participate in classical Lewis-base coordination to metal centers; it behaves as a cationic surfactant and forms ion pairs with anions. In solution it readily adsorbs to negatively charged surfaces (e.g., cell membranes, anionic polymers) and can form mixed aggregates or complexes with anionic species. The chloride counter-ion is exchangeable in ion-exchange processes but the cationic ammonium center remains permanently charged under normal conditions.
Reactivity and Stability
Chemical reactivity is dominated by the stability of the quaternary ammonium centre and the relatively robust aromatic–ether bonds. The substance is incompatible with strong oxidizing agents and with anionic surfactants/soaps (mutual inactivation and precipitation). It can react with nitrates and certain inorganic salts; strong acids at higher concentrations can precipitate the material from solution when concentrations exceed a few percent. The ether linkages are relatively resistant to hydrolysis under neutral conditions but may be cleaved under strongly acidic or strongly nucleophilic conditions or at elevated temperatures. The material is light-sensitive to some extent and should be kept protected from prolonged exposure to light to minimize degradation.
Molecular Parameters
Molecular Weight and Composition
Molecular formula: \(\mathrm{C}{27}\mathrm{H}_2\).}\mathrm{ClNO
Molecular weight: \(448.1\,\mathrm{g}\,\mathrm{mol}^{-1}\).
Exact/monoisotopic mass: 447.2904073 (reported).
Heavy atom count: 31.
Topological polar surface area (TPSA): 18.5.
Formal (net) charge: 0 (ionic pair consisting of a permanently charged quaternary ammonium cation and chloride anion).
Hydrogen-bond donor count: 0; hydrogen-bond acceptor count: 3.
Rotatable bond count: 12.
Complexity: 466.
These computed and measured parameters reflect an amphiphilic molecule with a permanently charged headgroup and substantial hydrophobic volume; the modest TPSA and lack of hydrogen-bond donors are consistent with membrane-associating behaviour rather than extensive aqueous hydrogen-bonding.
LogP and Ionization State
Reported LogP: 4.0 (reported value). Interpretation of octanol–water partition coefficients for quaternary ammonium salts requires caution: the cationic, ion-paired nature of benzethonium chloride means that apparent partitioning can depend strongly on counter-ion exchange, ionic strength, and experimental method. The intrinsic chemical state in typical use is a permanently charged ammonium cation paired with chloride; biological membrane partitioning is therefore governed by surfactant-driven adsorption and ion-pairing rather than neutral-molecule diffusion.
Identifiers and Synonyms
Registry Numbers and Codes
CAS (as shown in the heading): 23-11-9 (use this string when citing CAS).
Molecular formula (alternate): C27H42ClNO2 (as plain text when required).
InChIKey: UREZNYTWGJKWBI-UHFFFAOYSA-M
InChI: InChI=1S/C27H42NO2.ClH/c1-26(2,3)22-27(4,5)24-13-15-25(16-14-24)30-20-19-29-18-17-28(6,7)21-23-11-9-8-10-12-23;/h8-16H,17-22H2,1-7H3;1H/q+1;/p-1
SMILES: CC(C)(C)CC(C)(C)C1=CC=C(C=C1)OCCOCCN+(C)CC2=CC=CC=C2.[Cl-]
EC (European Community) number: 204-479-9
UNII: PH41D05744
ChEBI: CHEBI:31264
ChEMBL: CHEMBL221753
NSC: 755908 (also NSC-20200 and NSC-755908 found among historical identifiers)
RXCUI: 40036
(Where plain-text identifiers are required—SMILES, InChI, InChIKey—they are provided above without MathJax.)
Synonyms and Structural Names
Common and depositor-supplied synonyms reported include: Benzethonium chloride; Hyamine 1622; Phemeride; Phemerol; Quatrachlor; Hyamine; Benzyldimethyl(2-(2-(p-(1,1,3,3-tetramethylbutyl)phenoxy)ethoxy)ethyl)ammonium chloride; p-Diisobutylphenoxyethoxyethyl dimethyl benzyl ammonium chloride; BZT; Benzetonio cloruro; Benzyldimethyl-[2-[2-[4-(2,4,4-trimethylpentan-2-yl)phenoxy]ethoxy]ethyl]azanium chloride; and numerous trade and formulation names in product lists. This compound is also listed under pharmacopoeial grades and reference standards (e.g., USP/EP/JP grades in commercial practice).
Industrial and Commercial Applications
Use as Salt Form or Excipient
Benzethonium chloride functions primarily as an active cationic surfactant with antiseptic, disinfectant and preservative activity. Its quaternary ammonium chloride form provides both water solubility and surface activity, supporting its use as an antimicrobial active ingredient as well as a preservative or excipient in topical formulations. Pharmaceutical and cosmetic applications use pharmacopeial grades (BP, EP, JP, USP) where specified; the salt form is the usual commercial form for formulation and quality control.
Representative Use Cases
- Topical antiseptic and disinfectant in wound care and skin cleansers.
- Preservative in cosmetic and pharmaceutical preparations (concentrations governed by regulatory/formulation limits). For example, it is authorized in some hand-sanitizer formulations up to a specified percent by weight of the finished product.
- Cationic detergent and germicide for cleaning utensils and equipment (food and dairy industry), and as an algaecide in some pool treatments.
- Veterinary topical antiseptic preparations and udder/teat washes at dilute concentrations for disinfection.
- Additive in certain mouthwash formulations, and as an ingredient in some deodorant and dandruff-control products.
- Historically used as a spermicide and as an auxiliary reagent in laboratory assays (e.g., protein determination), although such applications are dictated by regulatory and safety considerations.
If a concise application summary is required beyond the general properties above, selection is typically driven by its surface-acting antimicrobial properties, solubility profile, and compatibility with intended formulation components (not compatible with anionic surfactants/soaps).
Safety and Handling Overview
Toxicological Considerations
Benzethonium chloride is an active biocide with documented acute toxicity by ingestion and irritation/corrosive effects on eyes and skin at sufficiently high concentrations. Key toxicological characteristics reported include: potential for severe eye damage at concentrations in the 0.1–1% range, skin irritation and contact dermatitis with repeated exposure, neurotoxic effects at high systemic exposures (including central nervous system depression and convulsions), and hemolytic/methemoglobinemic events in extreme cases. Fatal oral doses have been reported in the low-gram range (reported fatal dose by ingestion approximately \(1\text{--}3\,\mathrm{g}\)). Clinical first-aid measures for exposure include immediate irrigation of eyes and skin, removal of contaminated clothing, and prompt medical attention for ingestion or significant inhalation exposure; do not induce vomiting for corrosive ingestions and seek medical care immediately.
Environmental toxicity: the compound is toxic to aquatic organisms and should not be released to the environment; biodegradation can be limited under nonadapted conditions.
Note on classification: hazard statements and categories reported in notified classifications include acute oral toxicity, skin corrosion/irritation and serious eye damage/irritation, and acute and long-term aquatic toxicity. Exact classification and precautionary labeling vary by jurisdiction and formulation; product-specific Safety Data Sheets (SDS) should be consulted for regulatory hazard codes and workplace control measures.
Storage and Handling Guidelines
Handling: minimize dust generation when handling the solid; use appropriate engineering controls (local exhaust, containment) and personal protective equipment—chemical-resistant gloves, splash goggles or face shield, and suitable respiratory protection if airborne concentrations are possible. For handling concentrated solutions, use acid/organic vapor/acid gas cartridge respirators where indicated and impervious gloves; change gloves immediately if contamination or damage occurs.
Storage: store in a cool, well-ventilated area, protected from light and moisture; keep containers tightly closed and segregated from incompatible materials (strong oxidizers, anionic detergents/soaps, nitrates). Store away from foodstuffs and drain/sewer access. Some reports recommend refrigerated storage for long-term stability of neat material.
Spill and disposal: dampen powder to suppress dust and sweep into suitable containers for disposal; avoid releases to the environment. Contaminated absorbents and waste should be collected and disposed of according to applicable local regulations.
Firefighting: combustible material that can generate irritating/toxic gases on thermal decomposition (acid gases and nitrogen oxides); use extinguishing media appropriate for surrounding fire (water spray, foam, CO2, dry chemical); firefighters should wear full protective equipment and self-contained breathing apparatus.
For detailed hazard, transport and regulatory information, users should refer to the product-specific Safety Data Sheet (SDS) and local legislation.
Safety and Handling Overview (continued)
First Aid and Emergency Measures (summary)
- Inhalation: move to fresh air; seek medical attention if symptoms occur.
- Skin contact: remove contaminated clothing; wash affected areas with soap and water; seek medical attention for severe irritation or burns.
- Eye contact: flush eyes with copious water for at least 20–30 minutes and obtain immediate medical attention.
- Ingestion: do not induce vomiting; if conscious, rinse mouth and give small amounts of water to dilute and seek immediate medical attention.
These measures summarize commonly reported responses; follow institutional emergency procedures and local medical advice.
