P-Anisidine (104-94-9) Physical and Chemical Properties
P-Anisidine
Primary aromatic amine (4‑methoxyaniline) used as an analytical reagent and intermediate in synthesis, commonly procured for process chemistry, formulation and QC workflows.
| CAS Number | 104-94-9 |
| Family | Anisoles (substituted anilines) |
| Typical Form | Powder or crystalline solid |
| Common Grades | BP, EP, JP, USP |
P‑Anisidine is a primary aromatic amine of the anisole family; structurally it is an aniline ring bearing a para‑methoxy substituent and has the empirical formula \(\ce{C7H9NO}\). The structure comprises a phenyl ring substituted at the 4‑position by a methoxy group and at the 1‑position by an amino group, giving a resonance‑stabilized aromatic amine with an electron‑donating OCH3 group conjugated to the aniline nitrogen. This electronic arrangement increases ring electron density relative to aniline, alters basicity of the amino function relative to unsubstituted aniline, and affects both nucleophilicity and oxidation pathways typical for para‑substituted anilines.
Physicochemical behaviour is dominated by the combination of an aromatic primary amine and an ether (methoxy) substituent. The molecule is weakly polar (topological polar surface area \(= 35.3\)), with a small hydrogen‑bond donor count (1) and modest hydrogen‑bond acceptor capacity (2). Measured partition coefficients (log Kow/logP ≈ 0.9–0.95) indicate low to moderate lipophilicity; the basic amino group (reported \(\mathrm{p}K_a = 5.36\) at \(25\,^\circ\mathrm{C}\)) means the compound is partially protonated under mildly acidic conditions, increasing aqueous solubility and decreasing volatility under those conditions. The para‑methoxy substituent stabilizes cationic and radical intermediates to some extent, influencing reactivity in electrophilic substitution, oxidative coupling and N‑oxidation pathways.
P‑Anisidine is used industrially as an intermediate in dye manufacture and as a chemical reagent (notably in analytical detection of aldehydes and ketones). It is commercially available in multiple analytical and technical grades. Common commercial grades reported for this substance include: BP, EP, JP, USP.
Basic Physical Properties
Density
Reported values for bulk density and specific gravity include: \(1.07\) (unit context: g·cm⁻³ reported as "1.07 g/cm³") and "1.071 at 135 °F" / "1.071 at 57 °C/4 °C". These values indicate a material denser than water in the consolidated solid form and some reported liquid densities in the heated state; process and temperature conditions should be considered when using any single density value for equipment design.
Melting Point
Reported melting (or solid–liquid transition) temperatures include: \(57.2\,^\circ\mathrm{C}\) and "135 °F" as equivalent reported entries. Expect a crystalline, yellow‑to‑brown solid at ambient conditions.
Boiling Point
Reported boiling points under atmospheric pressure include: \(243\,^\circ\mathrm{C}\) (reported also as "243.00 °C. @ 760.00 mm Hg") and corresponding Fahrenheit values "469 °F" and "475 °F" in some records. Use the explicit \(243\,^\circ\mathrm{C}\) (760 mmHg) figure when planning distillation or vapor‑handling operations.
Vapor Pressure
P‑Anisidine has low vapour pressure consistent with a low volatility solid/liquid at ambient temperature. Representative reported values: - less than \(0.1\,\mathrm{mmHg}\) at \(68\,^\circ\mathrm{F}\), - \(3.0\times10^{-2}\,\mathrm{mmHg}\) at \(20\,^\circ\mathrm{C}\) (reported as "3.0X10-2 mm Hg at 20 °C"), - vapor pressure reported as \(0.03\,\mathrm{mmHg}\) in another report, - vapour pressure reported as \(2\) Pa at \(20\,^\circ\mathrm{C}\) in one dataset, - and "0.006 mmHg (77 °F)" in an alternative listing. These values reflect low equilibrium volatility at standard ambient temperatures but do not preclude significant airborne exposure in heated or aerosolized operations.
Flash Point
Reported flash points vary with measurement method and sample condition. Reported values include \(5\,^\circ\mathrm{C}\) (a low value in one listing), "41 °F" in another, and "122 °C (251.6 °F) (closed cup)" in a separate record. Because reported flash points differ substantially between sources, treat the material as combustible and implement standard flammable‑liquid controls (elimination of ignition sources, grounding/bonding, temperature control) until product‑specific data (SDS) for the supplied batch are confirmed.
Chemical Properties
Solubility and Phase Behavior
Aqueous solubility reports are variable depending on pH and measurement units. Representative reported values include: - "In water, 2.10X10+4 mg/L at 20 °C" (reported numerical form), - "21 mg/mL at 20 °C" which is numerically consistent with the above, - "Solubility in water, g/100ml at 20 °C: 2.2 (moderate)", - and "less than 1 mg/mL at 68 °F" in an alternate listing. Other solvent solubilities: reported soluble in acetone and benzene; very soluble in diethyl ether and ethanol. The amino group and its acid‑base equilibria strongly influence water solubility: protonation increases aqueous solubility near and below the \(\mathrm{p}K_a\) (\(\mathrm{p}K_a = 5.36\) at \(25\,^\circ\mathrm{C}\)), whereas the neutral free base has limited water solubility but good solubility in many organic solvents.
Phase behaviour: p‑Anisidine is a crystalline solid at ambient conditions (yellow to brown crystals) and melts above room temperature. In formulations the compound may form aerosols or dusts if dry and should be controlled to avoid inhalation exposures.
Reactivity and Stability
P‑Anisidine is a primary aromatic amine bearing an electron‑donating methoxy group; reactivity considerations include: - Sensitivity to strong oxidizing agents: aromatic amines are readily oxidized, potentially producing hazardous, colored, or polymeric by‑products and nitrogen‑oxide fumes when decomposed by heat. - Incompatibilities with strong acids, strong bases, chloroformates and other acylating agents; reactions with aldehydes/ketones can form imine or azo coupling products in situ. - Thermal decomposition can generate nitrogen oxides and other toxic fumes; the compound may be sensitive to heat, light and moisture under some conditions. Storage and handling should avoid contact with oxidizers and materials that promote uncontrolled decomposition or nitration.
Thermodynamic Data
Standard Enthalpies and Heat Capacity
No experimentally established value for this property is available in the current data context.
Molecular Parameters
Molecular Weight and Formula
Molecular formula: \(\ce{C7H9NO}\).
Molecular weight: \(123.15\ \mathrm{g}\,\mathrm{mol}^{-1}\).
Exact/monoisotopic mass: \(123.068413911\) (reported as ExactMass / MonoisotopicMass).
Other computed descriptors: heavy atom count = 9; formal charge = 0; molecular complexity = 77.
LogP and Polarity
Reported partitioning descriptors: XLogP = 0.9 (computed) and log Kow/logP reported as 0.95 in experimental summaries. Topological polar surface area (TPSA) = 35.3 Ų. These values indicate low-to-moderate lipophilicity with sufficient polarity for limited aqueous solubility in the neutral form and increased solubility upon protonation.
Structural Features
- Functional groups: primary aromatic amine (–NH2) at the para position to a methoxy (–OCH3) substituent on a benzene ring.
- Hydrogen bonding: one H‑bond donor (NH2) and two H‑bond acceptors (O and N).
- Rotatable bond count: 1 (typically the bond linking the methoxy substituent oxygen to the methyl group or the amine substituent orientation).
- Electronic effects: the para‑methoxy group is an electron‑donating group (resonance and inductive effects) that increases electron density of the ring and the amino nitrogen, affecting basicity (observed \(\mathrm{p}K_a = 5.36\)), nucleophilicity and susceptibility to oxidative pathways relative to unsubstituted aniline.
Identifiers and Synonyms
Registry Numbers and Codes
- CAS Registry Number: 104-94-9
- InChI:
InChI=1S/C7H9NO/c1-9-7-4-2-6(8)3-5-7/h2-5H,8H2,1H3 - InChIKey:
BHAAPTBBJKJZER-UHFFFAOYSA-N - SMILES:
COC1=CC=C(C=C1)N - EC numbers reported in datasets:
203-254-2and249-496-2 - UN number (reported in some transport listings):
2431 - Additional registry identifiers reported:
UNII: 575917SNR4,RTECS: BZ5450000,ChEBI: CHEBI:82388,ChEMBL: CHEMBL295652.
(Only codes and registry numbers appearing in source information are listed here.)
Synonyms and Structural Names
Common synonyms reported include: 4‑methoxyaniline; 4‑anisidine; p‑anisidine; para‑anisidine; 4‑methoxybenzenamine; 4‑aminoanisole; p‑methoxyaniline; aniline, 4‑methoxy‑. These alternative names reflect the identical para‑substitution pattern and are used interchangeably in industrial and analytical contexts.
Industrial and Commercial Applications
Representative Uses and Industry Sectors
P‑Anisidine is used as an intermediate in dyestuff manufacture (azo dyes and related colourants) and as an analytical reagent for the detection of aldehydic and ketonic secondary oxidation products in fats and oils (i.e., as a derivatizing agent for carbonyl determination). Its use as an intermediate in organic synthesis and as a building block for specialty chemicals is typical for para‑substituted anilines.
Role in Synthesis or Formulations
In synthesis p‑anisidine serves as a nucleophilic aromatic amine for coupling reactions, reductive transformations (from nitro precursors), and as a precursor to protected or derivatized intermediates (e.g., hydrochloride salts). Its reactivity toward carbonyl compounds underlies its application in analytical test kits for measuring lipid oxidation products. Selection of p‑anisidine in formulations or synthetic sequences is typically driven by its para‑electron donation, the availability of the NH2 handle for acylation or diazo coupling, and handling considerations for toxicology and stability.
Safety and Handling Overview
Acute and Occupational Toxicity
P‑Anisidine is an aromatic amine with documented systemic toxicity. Acute toxicity values reported include:
- LD50 (rat, oral): 1400 mg/kg
- LD50 (rat, dermal): 3200 mg/kg
- LD50 (mouse, oral): 1410 mg/kg
Major toxicological concerns include irritation to skin, eyes and respiratory tract, and systemic effects on blood (including formation of methemoglobin and hemolytic effects such as Heinz body formation), kidneys and liver. Clinical signs reported with exposure include headache, dizziness, cyanosis and respiratory distress in severe cases. Chronic or repeated exposure has been associated with hematologic effects and organ toxicity in animal studies; carcinogenicity classifications are not conclusive (not classifiable in some evaluations).
Occupational exposure limits reported in industrial guidance include TWA values around \(0.5\ \mathrm{mg}\,\mathrm{m}^{-3}\) (skin designation) for an 8‑hour time‑weighted average; an IDLH of \(50\ \mathrm{mg}\,\mathrm{m}^{-3}\) has been cited in emergency guidance. Where airborne concentrations may approach or exceed these limits, engineering controls and respiratory protection are required.
First‑aid and emergency treatment principles: remove exposed persons from exposure, decontaminate skin and eyes with copious water, provide supportive care and oxygen for respiratory compromise, and treat methemoglobinemia (symptomatic) with appropriate clinical antidotes (e.g., methylene blue) under medical supervision. Do not induce emesis in ingestion without medical advice.
Storage and Handling Considerations
- Store containers tightly closed in a cool, dark, well‑ventilated area away from heat and ignition sources. Protect from light and strong oxidizing agents.
- Segregate from incompatible materials (strong oxidizers, strong acids/bases, acylating agents) and from food or feedstuffs.
- For transfer and storage of liquids, use grounded and bonded metal equipment and non‑sparking tools; containers should be equipped with pressure‑relief devices as appropriate.
- Control dust generation for the solid form; finely dispersed powders can form explosive dust/air mixtures. Use closed systems, local exhaust ventilation and explosion‑proof electrical equipment where dust or aerosol formation is possible.
- Personal protective equipment: impervious gloves, eye/face protection, protective clothing to prevent skin contact, and respiratory protection where engineering controls cannot maintain airborne concentrations below occupational limits. Emergency showers and eyewash stations should be available in areas of use.
- Firefighting: material is combustible; extinguish fires with dry chemical, CO2 or foam. Decomposition can emit toxic nitrogen oxides; use positive‑pressure self‑contained breathing apparatus for fire response.
For detailed hazard, transport and regulatory information, users should refer to the product‑specific Safety Data Sheet (SDS) and local legislation.
