4-NITROPHENETOLE

4-Nitrophenetole is a para-substituted aromatic nitro ether used primarily as an intermediate in the production of 4-ethoxyaniline, dyes, pigments, pharmaceutical intermediates, antioxidants, and other specialty chemicals.
It is also known as p-Nitrophenetole and 1-ethoxy-4-nitrobenzene.
Commercial 4-Nitrophenetole is generally supplied as a pale-yellow to yellow or yellow-orange crystalline solid. Its combination of a reducible nitro group and a stable ethoxy substituent makes it a useful building block for multistage aromatic synthesis.

CHEMICAL IDENTITY AND SYNONYMS

Chemical Name: 4-Nitrophenetole
IUPAC Name: 1-Ethoxy-4-nitrobenzene
CAS Number: 100-29-8
EC Number: 202-837-9
Molecular Formula: C8H9NO3
Molecular Weight: 167.16 g/mol
Chemical Class: Aromatic nitro ether
PubChem CID: 7495
RTECS Number: DA0600000
SMILES: CCOC1=CC=C(C=C1)N+[O-]
InChIKey: NWPKEYHUZKMWKJ-UHFFFAOYSA-N

Common names include p-Nitrophenetole, para-Nitrophenetole, 1-ethoxy-4-nitrobenzene, 4-ethoxynitrobenzene, p-ethoxynitrobenzene, 1-nitro-4-ethoxybenzene, 4-nitrophenyl ethyl ether, ethyl 4-nitrophenyl ether, ethyl p-nitrophenyl ether, p-nitrophenyl ethyl ether, p-nitroethoxybenzene, phenetole p-nitro-, and NSC 9812. The identity, formula, molecular weight, boiling point, and established synonyms are recorded in the reference chemical database.

The synonym 4-Nitrophenetol appears in some catalogs, but the compound is an ethyl aryl ether and does not contain a free phenolic hydroxyl group.

4-Nitrophenetole should not be confused with 2-nitrophenetole, 3-nitrophenetole, 4-nitrophenol, 4-nitroanisole, phenetole, or 4-ethoxyaniline. These compounds differ in substitution pattern, functionality, physical properties, reactivity, and downstream applications.

PHYSICAL AND CHEMICAL PROPERTIES

4-Nitrophenetole is a crystalline solid at normal room temperature. It melts close to 59°C and can therefore become liquid in warm processing or storage environments.

Appearance: Pale-yellow to yellow, yellow-orange, or off-white crystalline powder
Physical State: Solid at 20°C
Melting Range: Approximately 57–61°C
Boiling Point: Approximately 283°C at atmospheric pressure
Reduced-Pressure Boiling Point: Approximately 112–115°C at 3 mmHg
Density: Approximately 1.18–1.20 g/cm³
Flash Point: Approximately 134°C
Vapor Pressure: Very low at room temperature
Water Solubility: Practically insoluble
Log Pow: Approximately 2.5–2.6
Organic-Solvent Solubility: Soluble in acetone, benzene, ether, hot ethanol, and other suitable organic solvents
Exact Mass: 167.0582 Da
Topological Polar Surface Area: Approximately 55.1 Ų

A representative synthesis grade has a minimum purity of 98% by gas chromatography and a specified melting range of 57–61°C. Representative commercial specification

CHEMICAL FUNCTIONALITY

4-Nitrophenetole contains an electron-withdrawing nitro group and an electron-donating ethoxy group in the para positions of the aromatic ring. This substitution pattern influences its electronic properties, color, and behavior in reduction and aromatic-substitution reactions.

The most important transformation is reduction of the nitro group to a primary aromatic amine. Complete reduction produces 4-ethoxyaniline, also known as p-phenetidine.

Depending on the reduction system, nitroso and hydroxylamine intermediates may form before conversion to the amine. Process conditions must prevent accumulation of partially reduced intermediates because they can affect selectivity, color, catalyst performance, and thermal safety.

The aromatic ether is stable under many neutral processing conditions. Strong acids at elevated temperature can promote ether cleavage, while strong oxidizing or reducing agents can cause vigorous reactions.

PRODUCTION AND COMMERCIAL FORM

One established industrial route produces 4-Nitrophenetole through nucleophilic aromatic substitution of 4-chloronitrobenzene with ethanol in the presence of an alkali-metal hydroxide and a phase-transfer catalyst.

The nitro group activates the chlorine-bearing aromatic carbon toward substitution by ethoxide. Process control is designed to maximize conversion while limiting residual 4-chloronitrobenzene, 4-nitrophenol, and azo or azoxy by-products. This manufacturing approach is described in the industrial process patent.

Another route uses O-ethylation of 4-nitrophenol or an alkali-metal 4-nitrophenoxide. Suitable ethylating reagents convert the phenoxide oxygen into the ethyl ether, after which salts and unreacted starting materials are removed.

Controlled nitration of phenetole can also form 4-Nitrophenetole. Because the ethoxy group directs nitration toward the ortho and para positions, this route produces an isomer mixture and requires separation of the desired para isomer. Crystallization is facilitated by the distinct melting behavior of 4-Nitrophenetole.

The crude reaction product may be washed, neutralized, vacuum-distilled, and crystallized. The selected purification sequence depends on the manufacturing route and required limits for isomers, residual precursors, color, ash, and high-boiling impurities.

Commercial product is normally supplied as crystalline powder, granules, flakes, or solid lumps. Common synthesis grades have an assay of at least 98%, while higher-purity or application-specific material may be supplied with tighter controls on isomers and downstream catalyst poisons.

APPLICATIONS AND INDUSTRIES

Production of 4-ethoxyaniline

The principal downstream reaction of 4-Nitrophenetole is reduction to 4-ethoxyaniline, commonly known as p-phenetidine. Reduction may be performed using catalytic hydrogenation or another validated nitro-reduction system.

4-Ethoxyaniline is an aromatic amine intermediate used in dyes, pigments, pharmaceutical synthesis, antioxidants, and fine chemicals. Its established identity and role as a downstream intermediate are summarized in the 4-ethoxyaniline chemical record.

Catalytic hydrogenation requires control of hydrogen pressure, catalyst loading, mixing, temperature, reaction heat, and endpoint. Residual sulfur compounds, halides, metals, or other catalyst poisons in 4-Nitrophenetole can reduce hydrogenation rate or alter selectivity.

Dye and pigment intermediates

4-Nitrophenetole is used in dye and pigment chemistry mainly through conversion to 4-ethoxyaniline. The resulting aromatic amine can be diazotized and coupled with suitable aromatic components to produce azo structures.

The ethoxy substituent affects electron density, shade, solubility, and interaction with other substituents in the finished colorant. These characteristics support its use in selected textile dyes, pigments, and specialty colorants.

Colorant-intermediate grades require consistent para-isomer purity, low residual nitrophenol, controlled metals, and minimal colored high-boiling impurities. Small variations in impurity profile can affect coupling behavior and final shade.

Pharmaceutical and fine-chemical intermediates

4-Nitrophenetole is used as a building block in multistage synthesis of substituted aromatic amines and related fine chemicals. Its nitro group provides a protected route to primary amine functionality that can be introduced after other process operations.

After reduction, 4-ethoxyaniline can undergo acylation, alkylation, diazotization, condensation, or heterocycle-forming reactions. These transformations support selected pharmaceutical and specialty-chemical synthesis routes.

4-Nitrophenetole itself is an industrial intermediate and not an active pharmaceutical ingredient. Pharmaceutical applications require appropriate impurity control, trace-metal limits, documentation, and compliance with the quality system governing the final product.

Antioxidant and stabilizer intermediates

4-Nitrophenetole can serve as a precursor to 4-ethoxyaniline used in the manufacture of selected quinoline derivatives, antioxidants, and stabilizing additives.

Regulatory requirements for antioxidants vary according to their final industrial, feed, food-contact, or technical use. Procurement of 4-Nitrophenetole does not by itself establish approval of the downstream substance for a regulated application.

Specialty aromatic synthesis

The para ethoxy and nitro substitution pattern makes 4-Nitrophenetole useful in the preparation of substituted anilines, additional nitro derivatives, halogenated intermediates, azo compounds, and heterocyclic structures.

Further aromatic substitution can introduce additional functionality before or after reduction of the nitro group. Reaction sequence is selected according to the directing effects of the ethoxy and nitro substituents.

Research and analytical applications

High-purity 4-Nitrophenetole is used in organic-synthesis research, reduction studies, catalytic-method development, chromatographic method validation, and spectroscopic reference work.

Research-grade material may require confirmed identity by nuclear magnetic resonance, infrared spectroscopy, or mass spectrometry in addition to assay by gas chromatography or high-performance liquid chromatography.

GRADE SELECTION AND QUALITY PARAMETERS

A common commercial specification is at least 98% purity by gas chromatography with a melting range of 57–61°C. The required specification should reflect the manufacturing route and downstream transformation.

Important procurement parameters include:

Assay by gas chromatography or high-performance liquid chromatography
4-Nitrophenetole content
2-Nitrophenetole and 3-Nitrophenetole content
Residual 4-chloronitrobenzene
Residual 4-nitrophenol
Residual phenetole
Azo and azoxy by-products
Melting range
Appearance and color
Water content
Residual solvents
Chloride, sulfate, or other inorganic ions
Ash or nonvolatile residue
Trace metals
Particle size
Packaging configuration
Certificate of Analysis and Safety Data Sheet requirements

A narrow melting range supports assessment of purity and para-isomer consistency. A depressed or broad melting range can indicate isomer contamination, solvent retention, residual starting material, or other impurities.

For catalytic reduction, residual halides, sulfur compounds, and trace metals deserve particular attention. These substances can poison the catalyst, affect hydrogen uptake, increase filtration requirements, or alter finished 4-ethoxyaniline color.

For dye manufacture, color and high-boiling impurity control are important because colored contaminants can carry through the reduction and coupling stages.

PROCESSING CONSIDERATIONS

4-Nitrophenetole can be charged as a solid, melted, or dissolved in a compatible process solvent. The preferred method depends on reactor design, batch size, required temperature, and downstream chemistry.

Because its melting point is near 59°C, heated handling should use indirect temperature-controlled equipment. Localized overheating should be avoided, particularly during melting, vacuum distillation, or solvent removal.

Dust generation should be minimized during bag opening, charging, sampling, and transfer. Closed charging, contained transfer, or local exhaust ventilation improves worker protection and prevents product loss.

Nitro-group reduction is exothermic. Process development should address reaction calorimetry, gas–liquid mass transfer, hydrogen inventory, cooling capacity, catalyst filtration, pressure relief, and management of partially reduced intermediates.

Vacuum distillation reduces the temperature required for purification. Distillation should be performed only in equipment suitable for nitroaromatic compounds and with validated thermal-stability limits.

STORAGE AND HANDLING

4-Nitrophenetole should be stored in tightly closed containers in a cool, dry, dark, and well-ventilated area. Storage below approximately 15°C is recommended for some high-purity grades to preserve appearance and quality.

The product should be protected from excessive heat, direct sunlight, moisture, strong oxidizing agents, strong reducing agents, and incompatible reactive chemicals.

Storage temperatures above the melting range can convert the product into a liquid and increase the possibility of leakage from packaging intended for solids. Warehouses and transportation conditions should therefore account for seasonal temperatures.

Operators should avoid inhaling dust and prevent ingestion or prolonged skin contact. Chemical-resistant gloves, protective clothing, and safety goggles should be used during handling.

SAFETY AND HAZARD INFORMATION

Current classifications for 4-Nitrophenetole can identify the material as potentially harmful if swallowed and toxic to aquatic life with long-lasting effects. Current hazard classification

Dust can irritate the eyes, skin, nose, and respiratory tract. Appropriate hygiene and exposure controls are required even when a supplied grade has a limited formal hazard classification.

4-Nitrophenetole is a combustible organic solid with a flash point around 134°C. Finely divided material should be kept away from ignition sources, and dust accumulation should be prevented.

Heating to decomposition can generate nitrogen oxides, carbon monoxide, carbon dioxide, smoke, and other irritating or toxic fumes.

The product must not be released into drains, soil, groundwater, or surface water. Waste and contaminated packaging should be managed through an approved hazardous-waste procedure.

FIRST AID

Inhalation: Move the affected person to fresh air and keep the person at rest. Obtain medical attention if coughing, headache, dizziness, breathing discomfort, or other symptoms develop.

Skin Contact: Remove contaminated clothing and wash the affected area thoroughly with soap and water. Obtain medical advice if irritation or other symptoms persist.

Eye Contact: Rinse cautiously with clean water for at least 15 minutes. Remove contact lenses when present and easy to remove, continue rinsing, and obtain medical attention if irritation persists.

Ingestion: Rinse the mouth and contact a poison center or physician. Do not induce vomiting unless instructed by qualified medical personnel.

FIRE AND SPILL RESPONSE

Suitable extinguishing media include dry chemical powder, foam, carbon dioxide, and water fog. Water spray may be used to cool exposed containers.

Firefighters should use appropriate protective clothing and self-contained breathing apparatus because burning nitroaromatic material can release toxic nitrogen-oxide fumes.

For spills, restrict access, eliminate ignition sources, and avoid generating airborne dust. Collect the solid mechanically using compatible non-sparking equipment and place it in labeled containers.

Residues should not be washed into drains.
Contaminated material must be disposed of according to applicable chemical-waste and environmental regulations.

TRANSPORT INFORMATION

4-Nitrophenetole in its commonly supplied solid form is generally not assigned a specific UN dangerous-goods number by many current supplier transport classifications.

The final transport classification must follow the Safety Data Sheet for the actual grade, quantity, packaging, destination, and mode of transport.

PACKAGING AND SUPPLY

4-Nitrophenetole can be supplied in sealed bags, lined fiber drums, plastic drums, metal drums, or other compatible packaging according to grade and quantity.

Packaging should protect the product from moisture, contamination, light, excessive temperature, and physical loss. Liners and closures must remain suitable if the product encounters temperatures close to its melting point.

Ataman Kimya supports 4-Nitrophenetole procurement for 4-ethoxyaniline production, dyes, pigments, pharmaceutical intermediates, antioxidant intermediates, fine chemicals, and research applications. Product selection can be coordinated according to assay, para-isomer purity, melting range, color, residual nitrophenol, residual chloronitrobenzene, catalyst-poison limits, packaging, and documentation requirements.

For specifications, availability, packaging options, and commercial inquiries, contact Ataman Kimya.

Phone: +90 216 577 10 10
Email: info@atamankimya.com