3-CHLORO-P-TOLYL ISOCYANATE

3-Chloro-p-tolyl isocyanate is a moisture-sensitive aromatic monoisocyanate used primarily as an intermediate in substituted phenylurea synthesis.
3-Chloro-p-tolyl isocyanate is particularly associated with the manufacture of chlorotoluron and other compounds containing the 3-chloro-4-methylphenyl urea structure.
The electrophilic isocyanate group reacts efficiently with amines and can also form carbamates through controlled reactions with alcohols or phenols.

CHEMICAL IDENTITY AND COMMON NAMES

3-Chloro-p-tolyl isocyanate is the common registry name for the compound systematically described as 3-chloro-4-methylphenyl isocyanate.
The methyl group is para to the isocyanate-bearing position, while the chlorine atom occupies the adjacent meta position.
The product should not be confused with 3-chlorophenyl isocyanate, p-tolyl isocyanate, or chlorotoluene diisocyanates.

Synonyms and Common Names: 3-Chloro-p-tolyl isocyanate, 3-Chloro-p-tolylisocyanate, 3-Chloro-4-methylphenyl isocyanate, 3-Chloro-4-methylphenylisocyanate, 2-Chloro-4-isocyanato-1-methylbenzene, 2-Chloro-4-isocyanatotoluene, 4-Isocyanato-2-chlorotoluene, 3-Chloro-4-methyl-1-isocyanatobenzene, Isocyanic acid 3-chloro-4-methylphenyl ester, Isocyanic acid, 3-chloro-4-methylphenyl ester, CMPI

TECHNICAL IDENTIFICATION

CAS Number: 28479-22-3
EC / EINECS Number: 249-050-7
Molecular Formula: C8H6ClNO
Molar Mass: 167.59 g/mol
SMILES: Cc1ccc(cc1Cl)N=C=O
InChIKey: UKTKKMZDESVUEE-UHFFFAOYSA-N
Chemical Class: Aromatic monoisocyanate
Functional Group: Isocyanate
Isocyanate Functionality: 1
Theoretical NCO Content: Approximately 25.07% by mass
NCO Equivalent Weight: 167.59 g/eq

PHYSICAL AND CHEMICAL PROPERTIES

Appearance: Clear, colorless to pale yellow material
Physical State: Low-melting solid or liquid depending on temperature
Odour: Pungent and lachrymatory
Melting Point: 20–24 °C
Boiling Point: Approximately 225 °C at atmospheric pressure
Reduced-Pressure Boiling Point: Approximately 107 °C at 3 mmHg
Density: Approximately 1.224 g/mL at 25 °C
Relative Density: Approximately 1.23
Refractive Index: Approximately 1.554–1.558
Flash Point: Approximately 109–110 °C, closed cup
Vapour Pressure: Approximately 0.2 mbar at 20 °C
Water Reactivity: Moisture-sensitive and reactive toward water
Storage Temperature: 2–8 °C for high-purity packaged material

The melting range lies close to normal room temperature.
Pure material can therefore crystallise in a cool room and return to a liquid state when warmed carefully above the melting range.
Technical liquid grades can remain fluid at temperatures where higher-purity material begins to crystallise.

FUNCTIONAL CHARACTERISTICS

The carbon atom of the N=C=O group is strongly electrophilic and reacts readily with nucleophilic compounds.
Primary amines produce N,N′-disubstituted ureas containing the 3-chloro-4-methylphenyl group.
Secondary amines produce more highly substituted ureas without leaving an NH group on the amine-derived side.
Alcohols and phenols can react with 3-Chloro-p-tolyl isocyanate to form aromatic carbamates.

These reactions generally require more controlled activation than the corresponding reactions with amines.
The chlorine and methyl substituents remain attached to the aromatic ring during normal urea and carbamate formation.
They influence the electronic character, steric profile, lipophilicity, and biological activity of the resulting molecule.
Because 3-Chloro-p-tolyl isocyanate contains only one isocyanate group, it is primarily used to construct discrete molecules rather than crosslinked polyurethane networks.

REACTION WITH WATER

Water reacts with the isocyanate group and initially generates an unstable carbamic acid.
The carbamic acid decomposes into 3-chloro-4-methylaniline and carbon dioxide.
The resulting aromatic amine can react with additional 3-Chloro-p-tolyl isocyanate to form a symmetrical diarylurea.
Moisture exposure therefore causes assay loss, carbon dioxide evolution, solid formation, turbidity, and pressure development in restricted equipment.
Dry equipment, dry solvents, moisture-tight packaging, and a dry inert atmosphere preserve the reactive NCO content.

PRODUCTION AND COMMERCIAL FORM

Industrial production normally begins with 3-chloro-4-methylaniline, also known as 2-chloro-4-aminotoluene.
The aromatic amine is reacted with phosgene in a closed, dry process system.
The reaction proceeds through carbamoyl chloride intermediates and releases hydrogen chloride as the isocyanate structure is formed.
Excess phosgene, hydrogen chloride, and process solvent are removed through controlled recovery and purification operations.
Reduced-pressure distillation provides purified 3-Chloro-p-tolyl isocyanate while limiting prolonged high-temperature exposure.
The associated aromatic amine can be prepared by reduction of 3-chloro-4-methylnitrobenzene.
Specialised catalytic carbonylation routes can produce the isocyanate directly from the corresponding nitroaromatic compound.
Commercial material is available as a technical intermediate and as higher-purity synthesis material.
Its low melting point permits handling as a solid, partially crystallised material, or liquid according to grade and temperature.

APPLICATIONS AND INDUSTRIES

Chlorotoluron manufacture

3-Chloro-p-tolyl isocyanate is a direct intermediate in the production of chlorotoluron.
Reaction with dimethylamine forms N′-(3-chloro-4-methylphenyl)-N,N-dimethylurea, the chemical structure of chlorotoluron.
This conversion uses the high reactivity of the isocyanate group to establish the substituted phenylurea linkage.
Controlled addition and heat removal support high conversion while limiting local excesses of either reactant.
Low water content is essential because hydrolysis consumes the isocyanate and generates 3-chloro-4-methylaniline and diarylurea impurities.
Residual amine, moisture, isomeric aromatic compounds, and hydrolysis products influence the final agrochemical purification requirement.

Substituted phenylurea synthesis

3-Chloro-p-tolyl isocyanate reacts with primary and secondary amines to produce substituted phenylureas.
Applicable reactants include aliphatic amines, cyclic amines, benzylamines, aromatic amines, and structurally complex amino intermediates.
The reaction installs the complete 3-chloro-4-methylphenyl side of the urea group in a single synthetic step.
This approach is used in fine-chemical development, agrochemical research, biological screening, and preparation of specialised molecular libraries.
The selection of amine, reaction medium, temperature, and stoichiometry determines substitution pattern and purification behaviour.

Agrochemical intermediate production

The 3-chloro-4-methylphenyl group is an established structural component in phenylurea agrochemical chemistry.
3-Chloro-p-tolyl isocyanate provides this aromatic group together with the reactive carbonyl nitrogen unit required for urea formation.
Technical intermediate grades are selected for closed manufacturing processes in which consistent assay, water content, free amine, and isomer profile are important.
Process monitoring focuses on isocyanate conversion, residual starting materials, hydrolysis products, and heavy impurities.

Pharmaceutical and medicinal chemistry

3-Chloro-p-tolyl isocyanate is used as an aryl-isocyanate building block in the preparation of experimental bioactive urea derivatives.
The urea group can provide hydrogen-bonding capacity and a defined spatial relationship between aromatic and amine-derived molecular fragments.
The chlorine and methyl substituents provide a useful combination of steric, electronic, and lipophilic effects during structure-activity studies.
This application is concentrated in research, lead optimisation, and specialised fine-chemical synthesis rather than use of the isocyanate as an active pharmaceutical ingredient.

Carbamate synthesis

3-Chloro-p-tolyl isocyanate can react with alcohols and phenols to form N-(3-chloro-4-methylphenyl) carbamates.
Carbamate formation is useful when the target molecule requires an oxygen-linked substituent rather than an amine-derived urea group.
Catalysis, controlled heating, and moisture exclusion support efficient conversion with less nucleophilic alcohol and phenol reactants.
The resulting carbamates are used as specialised research compounds and intermediates in organic synthesis.

Chemical research and process development

The compound is used to evaluate aromatic isocyanate reactivity, urea-forming reactions, carbamate synthesis, and moisture-control strategies.
Its single NCO group makes stoichiometry and reaction-product interpretation more straightforward than with multifunctional isocyanates.
3-Chloro-p-tolyl isocyanate can also serve as a reference intermediate during chlorotoluron process development and impurity identification.
Reaction progress can be followed through gas chromatography, NCO titration, or infrared monitoring of the isocyanate absorption band.

GRADE SELECTION AND PRODUCT SUITABILITY

Technical Intermediate Grade

Technical intermediate material is intended for closed agrochemical and fine-chemical manufacturing.
Important parameters include assay, water content, free 3-chloro-4-methylaniline, chlorinated aromatic isomers, colour, residual solvent, and hydrolysis products.

High-Purity Synthesis Grade

High-purity synthesis grades are commonly released at 97–98% assay by gas chromatography.
These grades support medicinal chemistry, controlled urea synthesis, carbamate preparation, analytical work, and catalyst evaluation.
A tight impurity profile reduces chromatographic interference and simplifies purification of high-value reaction products.

Low-Moisture Grade

Low-moisture material preserves the active isocyanate concentration and limits carbon dioxide evolution during processing.
This characteristic is particularly important for stoichiometrically sensitive reactions and products requiring low levels of aniline or diarylurea impurities.

Liquid-Handling Form

Material intended for liquid transfer is maintained above its melting range through dry, controlled, indirect warming.
The liquid form supports metered charging and closed transfer without changing the chemical identity.

FORMULATION AND PROCESS CONSIDERATIONS

3-Chloro-p-tolyl isocyanate should be processed in dry, closed equipment under an inert atmosphere.
Reaction vessels, transfer lines, solvents, and receiving materials should be free from water and uncontrolled nucleophilic contaminants.
Urea formation with amines is exothermic.

Metered addition, efficient agitation, and adequate heat removal control the reaction rate and temperature.
Dry aprotic solvents are suitable for solution-phase reactions when dilution is required.
The selected solvent must remain chemically inert toward the isocyanate group and compatible with the intended purification process.

Partial crystallisation can be reversed through dry, indirect warming slightly above the melting range.
Open flame, direct steam contact, and uncontrolled local heating are unsuitable for melting operations.
Infrared analysis can monitor disappearance of the characteristic NCO absorption near 2270 cm−1.

Gas chromatography provides direct information on residual 3-Chloro-p-tolyl isocyanate and volatile organic impurities.
NCO titration provides a functional assay that responds to the chemically active isocyanate content.

QUALITY, SPECIFICATIONS AND DOCUMENTATION

Appearance and colour provide rapid indicators of contamination, hydrolysis, oxidation, or extended thermal exposure.
Gas chromatographic assay establishes the concentration of the principal chemical component.
NCO titration measures active isocyanate functionality and can identify loss of reactivity that is not fully represented by a nonspecific purity measurement.
Karl Fischer analysis controls trace water before the material enters moisture-sensitive synthesis.

Free 3-chloro-4-methylaniline is important because it consumes isocyanate and can alter downstream product composition.
Diarylurea and other hydrolysis-derived solids can affect clarity, filtration, transfer, and final-product purity.
Additional controls include melting range, density, refractive index, residual solvent, acidity, colour, and isomeric chlorinated aromatic impurities.
A Certificate of Analysis should present batch-specific assay, appearance, and critical impurity results.

The Technical Data Sheet describes the physical form, storage conditions, processing characteristics, and principal specification parameters.
The Safety Data Sheet provides the hazard classification, exposure controls, emergency measures, storage requirements, and transport information.

SAFETY AND REGULATORY CONSIDERATIONS

Signal Word: Danger
Acute Inhalation Toxicity: Category 1
Skin Corrosion: Category 1B
Serious Eye Damage: Category 1
Respiratory Sensitisation: Category 1
Specific Target Organ Toxicity, Single Exposure: Category 3
Primary Target Organ: Respiratory system
Environmental Classification: Harmful to aquatic life with long-lasting effects

3-Chloro-p-tolyl isocyanate is fatal if inhaled.
The substance causes severe skin burns and serious eye damage.

Vapour or aerosol can cause respiratory irritation.
Inhalation exposure can cause allergic sensitisation, asthma symptoms, wheezing, chest tightness, or breathing difficulty.

The material has a pungent, tear-producing effect, but odour must not be used as an exposure-control method.
Closed processing, local exhaust ventilation, and strict prevention of vapour or aerosol release are required.
Personnel should wear chemically resistant gloves, protective clothing, chemical goggles, and a face shield.

Respiratory protection suitable for organic vapours and isocyanate exposure is required when enclosure and ventilation do not completely prevent inhalation.
Emergency eyewash and safety-shower facilities should be immediately accessible.

FIRST AID

Inhalation: Move the affected person to fresh air and keep the person comfortable for breathing.
Inhalation requires immediate medical attention because severe or delayed respiratory effects can occur.
Trained personnel should provide assisted ventilation with suitable resuscitation equipment if breathing stops.

Skin Contact: Remove contaminated clothing immediately and rinse the skin continuously with water for at least 15 minutes.
Obtain immediate medical attention for every significant skin exposure.

Eye Contact: Rinse cautiously and continuously with water for at least 15 minutes while holding the eyelids open.
Remove contact lenses when this can be done easily and obtain immediate ophthalmic treatment.

Ingestion: Rinse the mouth and do not induce vomiting.
Obtain immediate medical assistance because the material can cause corrosive injury to the mouth, oesophagus, and gastrointestinal tract.

Note to Physicians: Respiratory sensitisation and pulmonary symptoms can be delayed after exposure.
Treatment should address corrosive injury, respiratory irritation, bronchospasm, and sensitisation symptoms.

FIRE AND SPILL RESPONSE

Suitable extinguishing media include carbon dioxide, dry chemical powder, dry sand, and alcohol-resistant foam.
Water spray can cool unopened containers exposed to fire, but water must not enter product containers.

Thermal decomposition can release carbon monoxide, carbon dioxide, hydrogen chloride, and irritating isocyanate-containing fumes.
Firefighters require full protective equipment and positive-pressure self-contained breathing apparatus.
A spill area should be evacuated, isolated, and ventilated.

Only trained personnel wearing suitable chemical and respiratory protection should enter the contaminated area.
The liquid should be contained and absorbed with dry inert material.
Water should not be applied directly to the bulk spill because hydrolysis can release carbon dioxide and produce solid urea material.

Collected waste should be transferred to a compatible hazardous-waste container under controlled conditions.
Product and cleaning residues must be prevented from entering drains, soil, groundwater, or surface water.

HANDLING AND STORAGE

Handle 3-Chloro-p-tolyl isocyanate only in closed process equipment or an effective chemical fume enclosure.
Do not breathe vapour, mist, aerosol, or decomposition fumes.
Prevent all contact with the eyes, skin, and clothing.
Keep the container tightly closed under a dry inert atmosphere.

Store high-purity packaged material at 2–8 °C in a dry, locked, and well-ventilated chemical storage area.
Protect the product from moisture, humid air, excessive heat, and direct sunlight.
Segregate the material from water, alcohols, amines, strong acids, strong bases, and strong oxidising agents.

Warm crystallised material only through controlled indirect heating for the time required to obtain a transferable liquid.
Do not return exposed, sampled, or contaminated material to the original container.

PACKAGING AND PROCUREMENT CONSIDERATIONS

3-Chloro-p-tolyl isocyanate requires dry, moisture-tight, chemically compatible packaging with a secure closure and inert headspace.
Suitable formats include sealed small-volume packs and closed industrial containers designed for toxic, moisture-sensitive isocyanates.

Procurement specifications should define assay, active NCO content, water, free aromatic amine, colour, physical form, residual solvent, isomer profile, and hydrolysis-derived impurities.
The physical form at dispatch determines heating, unloading, sampling, and transport arrangements.
Pure solid material is transported under UN 3428, 3-Chloro-4-methylphenyl isocyanate, solid, Class 6.1, Packing Group II.

Technical liquid material is transported under UN 2236, 3-Chloro-4-methylphenyl isocyanate, liquid, Class 6.1, Packing Group II.
Ataman Kimya supports the sourcing of 3-Chloro-p-tolyl isocyanate for chlorotoluron manufacture, substituted phenylurea synthesis, carbamate chemistry, and fine-chemical research.
Technical and commercial requests can include the required assay, moisture limit, impurity profile, physical form, packaging, documentation, destination, and annual quantity.

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info@atamankimya.com