28479-22-3

Usage

Uses

Used in Chemical Synthesis:
3-Chloro-4-methylphenyl isocyanate is used as a key intermediate in the synthesis of various urea compounds, which have diverse applications in different industries. The synthesis of these urea compounds is facilitated by the reactive isocyanate group present in the molecule.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, 3-Chloro-4-methylphenyl isocyanate is used as a building block for the development of new drugs. The synthesized urea compounds can be further modified and optimized to create potential therapeutic agents for various medical conditions.
Used in Agrochemical Industry:
3-Chloro-4-methylphenyl isocyanate is also utilized in the agrochemical industry for the synthesis of compounds with pesticidal properties. The urea compounds derived from this isocyanate can be used to develop new pesticides or enhance the effectiveness of existing ones.
Used in Polymer Industry:
In the polymer industry, 3-Chloro-4-methylphenyl isocyanate can be used to synthesize urea-formaldehyde resins, which are widely used as adhesives, coatings, and molding materials. These resins offer excellent mechanical properties and thermal stability, making them suitable for various applications.
Used in Dye and Pigment Industry:
3-Chloro-4-methylphenyl isocyanate can be employed in the synthesis of dyes and pigments, where the urea compounds derived from this isocyanate can be used to create new colorants or improve the properties of existing ones.

Air & Water Reactions

Flammable. 3-Chloro-4-methylphenyl isocyanate decomposes in water. Substance will react with water (some violently) releasing flammable, toxic or corrosive gases and runoff.

Reactivity Profile

Isocyanates and thioisocyanates, such as 3-Chloro-4-methylphenyl isocyanate, are incompatible with many classes of compounds, reacting exothermically to release toxic gases. Reactions with amines, aldehydes, alcohols, alkali metals, ketones, mercaptans, strong oxidizers, hydrides, phenols, and peroxides can cause vigorous releases of heat. Acids and bases initiate polymerization reactions in these materials. Some isocyanates react with water to form amines and liberate carbon dioxide. Base-catalysed reactions of isocyanates with alcohols should be carried out in inert solvents. Such reactions in the absence of solvents often occur with explosive violence, [Wischmeyer(1969)].

Health Hazard

TOXIC; inhalation, ingestion or contact (skin, eyes) with vapors, dusts or substance may cause severe injury, burns or death. Contact with molten substance may cause severe burns to skin and eyes. Reaction with water or moist air will release toxic, corrosive or flammable gases. Reaction with water may generate much heat that will increase the concentration of fumes in the air. Fire will produce irritating, corrosive and/or toxic gases. Runoff from fire control or dilution water may be corrosive and/or toxic and cause pollution.

Fire Hazard

Combustible material: may burn but does not ignite readily. Substance will react with water (some violently) releasing flammable, toxic or corrosive gases and runoff. When heated, vapors may form explosive mixtures with air: indoors, outdoors and sewers explosion hazards. Most vapors are heavier than air. They will spread along ground and collect in low or confined areas (sewers, basements, tanks). Vapors may travel to source of ignition and flash back. Contact with metals may evolve flammable hydrogen gas. Containers may explode when heated or if contaminated with water.

Potential Exposure

This material is used in organic synthesis.

Shipping

UN22363-Chloro-4-methylphenyl isocyanate, liquid, Hazard Class: 6.1; Labels: 6.1-Poisonous materials.

Incompatibilities

May form explosive mixture with air. Isocyanates are highly flammable and reactive with many compounds, even with themselves. Incompatible with oxidizers (chlorates, nitrates, peroxides, permanganates, perchlorates, chlorine, bromine, fluorine, etc.); contact may cause fires or explosions. Reaction with moist air, water or alcohols may form amines and insoluble polyureas and react exothermically, releasing toxic, corrosive, or flammable gases, including carbon dioxide; and, at the same time, may generate a violent release of heat increasing the concentration of fumes in the air. Incompatible with amines, aldehydes, alkali metals, ammonia, carboxylic acids, caprolactum, alkaline materials, glycols, ketones, mercaptans, hydrides, organotin catalysts, phenols, strong acids, strong bases, strong reducing agents such as hydrides, urethanes, ureas. Elevated temperatures or contact with acids, bases, tertiary amines, and acyl-chlorides may cause explosive polymerization. Attacks some plastics, rubber, and coatings. Contact with metals may evolve flammable hydrogen gas. May accumulate static electrical charges, and may cause ignition of its vapors. Do not store in temperatures above 30C/86F.

InChI:InChI=1/C8H6ClNO/c1-6-2-3-7(10-5-11)4-8(6)9/h2-4H,1H3

Upstream product

• 15545-48-9 N-(3-chloro-4-methylphenyl)-N,N-dimethylurea 
• 32315-10-9 bis(trichloromethyl) carbonate 
• 95-74-9 3-chloro-p-toluidine 

Downstream Products

• 21514-93-2 aziridine-1-carboxylic acid-(3-chloro-4-methyl-anilide) 
• 15545-48-9 N-(3-chloro-4-methylphenyl)-N,N-dimethylurea 
• 56407-33-1 1-(3-chloro-4-methyl-phenyl)-3,3-dimethyl-4-morpholin-4-yl-azetidin-2-one 
• 95707-12-3 <3-Chlor-4-methyl-phenylcarbamoylmercapto>-essigsaeure-methylamid 
• 91767-06-5 <3-Chlor-4-methyl-phenylcarbamoylmercapto>-essigsaeure-dimethylamid 
• 91767-05-4 <3-Chlor-4-methyl-phenylcarbamoylmercapto>-essigsaeure-aethylamid 
• 22546-25-4 C₁₀H₁₄ClN₃O 
• 22546-41-4 C₉H₁₂ClN₃O 
• 32496-46-1 (3-Chloro-4-methyl-phenyl)-carbamic acid 1,1-dimethyl-prop-2-ynyl ester 
• 64393-06-2 1-(3-Chlor-4-methyl-phenyl)-3-cyclopropyl-harnstoff 
• 145799-01-5 N-(3-Chloro-4-tolyl)-N¹-(1,2-dimethylimidazol-5-yl)urea 
• 107108-03-2 3-(N-3-Chloro-4-methylphenylureido)-5,6-dimethyl-1,2,4-triazine 
• 84833-12-5 2-Phenyl-thiazolidine-3-carboxylic acid (3-chloro-4-methyl-phenyl)-amide 
• 117015-67-5 N₆-(4-Methyl-3-chlorophenylcarbamoyl)-3-phenylisopropylsydnone imine 

Relevant academic research and scientific papers

Design, synthesis, and biological evaluation of novel substituted thiourea derivatives as potential anticancer agents for NSCLC by blocking K-Ras protein-effectors interactions

Mutation of the proto-oncogene K-Ras is one of the most common molecular mechanisms in non-small cell lung cancer. Many drugs for treating lung cancer have been developed, however, due to clinical observed K-Ras mutations, corresponding chemotherapy and targeted therapy for such mutation are not efficient enough. In this study, on the basis of the crystal structure of K-Ras, 21 analogues (TKR01–TKR21) containing urea or thiourea were rationally designed, which can effectively inhibit the lung cancer cell A549 growth. The designing of these compounds was based on the structure of K-Ras protein, and the related groups were replaced by bioisosteres to improve the affinity and selectivity. Biological testing revealed that compound TKR15 could significantly inhibit the proliferation of A549 cell with IC50 of 0.21 μM. Docking analysis showed that the TKR15 can effectively bind to the hydrophobic cavity and form a hydrogen bond with the Glu37. In addition, through flow apoptosis assay and immunofluorescence staining assay, it confirmed that this compound can inhibit A549 cell proliferation with the mechanism of blocking K-RasG12V protein and effector proteins interactions through the apoptotic pathway. In conclusion, our studies in finding novel potent compound (TKR15) with confirmed mechanism showed great potential for further optimisation and other medicinal chemistry relevant studies.

Discovery of novel anti-angiogenesis agents. Part 7: Multitarget inhibitors of VEGFR-2, TIE-2 and EphB4

Herein, we embarked on a structural optimization campaign aiming at the discovery of second generation anti-angiogenesis agents with our previously reported BPS-7 as lead compound. A library of 27 compounds has been afforded based on the highly conserved ATP-binding pocket of VEGFR-2, Tie-2, and EphB4. Several title compounds exhibited simultaneous inhibitory effects against three angiogenic RTKs. These compounds with a ‘triplet’ inhibition profile have been identified as novel anti-angiogenic and anticancer agents. The representative VDAU11 displayed prominent anti-angiogenic and anticancer potency and could be considered as a candidate for further optimization. These results indicate that N-(pyridin-2-yl)acrylamide could serve as a novel hinge-binding group of triple inhibitors.

With anti-tumor effect of a quinazoline-urea derivative and its application (by machine translation)

The present invention relates to a of the general formula (II) anti-tumor function of said quinazoline-urea derivative and its application. The definition of the substituent in the general formula (II) in the specification. This invention, in order to SUO draw non-Buddhist nun and Geftinat compounds as the precursor, retention of SUO draw non-Buddhist nun the pharmocology-carbamido; at the same time, such as in reserved [...] EGFR-TKIs Geftinat, synthesis, and obtain a series of quinazoline-urea derivatives, by the in vitro activity tests, some compounds exhibit excellent anti-tumor activity, such derivatives have high research and utility value. (II). (by machine translation)

Discovery of novel VEGFR-2 inhibitors. Part 5: Exploration of diverse hinge-binding fragments via core-refining approach

Pathological angiogenesis plays a critical role in numerous diseases including malignancy. VEGFR-2 is the central regulators in angiogenesis and has become a promising target for anticancer drug design. We have identified a novel biphenyl-aryl urea incorporated with salicyladoxime (BPS-7) as potent VEGFR-2 inhibitor. As a continuation to our previous research, various aromatic-heterocyclic were introduced as hinge-binding fragment via a core-refining approach. Interestingly, many compounds exhibited comparable VEGFR-2 inhibition to Sorafenib. In particular, 12e and 12o displayed excellent VEGFR-2 inhibitory activity with IC50 values of 0.50 nM and 0.79 nM, respectively. Several title compounds showed considerable antiproliferative activity against A549 and SMMC-7721 cells. In addition, molecular docking was performed to rationalize the efficiency of the better compounds. These results will be instructive for further inhibitor design and optimization.

A simple and efficient synthesis of diaryl ureas with reduction of the intermediate isocyanate by triethylamine

Thirty symmetrical diaryl urea derivatives were synthesised in moderate to excellent yields from arylamine and triphosgene with triethylamine as a reducing agent for the intermediate, isocyanate. It was significant that part of the products could be collected in almost quantitative yield without column chromatography. The procedure under mild reaction conditions was tolerant of a wide range of functional groups. The structures of the compounds were determined by NMR, MS and X-ray crystallographic analyses.

Kinetics and mechanism of hydrolysis of phenylureas

The hydrolysis of phenylureas has been found to be affected by temperature, pH and buffer concentration. Kinetic evidence suggests that the formation of phenylisocyanate, the initial product in the title reaction, occurs via an intermediate zwitterion. Depending on pH and buffer concentrations, the zwitterion can be produced through three parallel routes: at low pH, specific acid-general base catalysis, followed by slow deprotonation of a nitrogen atom by a general base; at high pH, specific basic-general acid catalysis, followed by slow protonation of a N atom by a general acid; at intermediate pH the reaction proceeds through a proton switch promoted by buffers. Bifunctional acid-base buffers such as HCO3-/CO32-, H2PO42- and CH3COOH/CH3COO- are very efficient catalysts. At high buffer concentration, as well as at pH 12, the breakdown of the zwitterion is rate-determining. The results are discussed in relation to recently published papers reporting different pathways.

A facile method for preparation of aromatic isocyanates using bis(trichloromethyl)carbonate

A facile synthesis of aromatic isocyanates using bis(trichloromethyl)carbonate (BTC) is reported with high yields of products. BTC is used to supply phosgene in situ in stoichiometric amounts.