79-22-1

Usage

Uses

Used in Pharmaceutical Industry:
Methyl chloroformate is used as a key intermediate in the synthesis of a new class of potent Cdk4 inhibitors for the treatment of cancer. These inhibitors have the potential to target and stop the growth of cancer cells, making them a promising therapeutic option for cancer patients.
Used in Organic Synthesis:
Methyl chloroformate is also used in the synthesis of Phorboxazole B, a complex natural product with potential biological activities. Its unique structure and properties make it an interesting target for organic synthesis and drug discovery efforts.

Production Methods

Prepared from phosgene and methyl alcohol.

Air & Water Reactions

Highly flammable. Gives off hydrochloric acid fumes in contact with moist air. Slightly soluble in water and decomposed by water to hydrochloric acid with evolution of heat.

Reactivity Profile

Methyl chloroformate is incompatible with water, strong oxidizing agents, alcohols, bases (including amines). Decomposes slowly in water to yield methanol, HCl, and CO2; reaction can be hazardous if water is hot. Attacks many metals especially in humid atmosphere [Handling Chemicals Safely 1980. p. 476]. May react vigorously or explosively if mixed with diisopropyl ether or other ethers in the presence of trace amounts of metal salts [J. Haz. Mat., 1981, 4, 291].

Hazard

Flammable, dangerous fire risk. Highly corrosive and irritant to skin and eyes.

Health Hazard

Methyl chloroformate is highly toxic upon inhalation and upon ingestion. A concentration of 1 mg/liter (190 ppm) has been lethal in 10 minutes. It is corrosive and irritating to skin.

Fire Hazard

Methyl chloroformate is very dangerous when exposed to heat sources, sparks, flame, or oxidizers. Methyl chloroformate will react with water or steam to produce toxic and corrosive fumes. Vapors may travel to a source of ignition and flash back. Withdraw immediately in case of rising sound from venting safety device or any discoloration of tank due to fire. Toxic fumes of phosgene are produced when the material is heated to decomposition. Heat or steam should be avoided.

Flammability and Explosibility

Flammable

Chemical Reactivity

Reactivity with Water: Reacts slowly, evolving hydrogen chloride (hydrochloric acid). Reaction can be hazardous if water is hot; Reactivity with Common Materials: Corrodes rubber; Stability During Transport: Stable; Neutralizing Agents for Acids and Caustics: Flush with water, rinse with sodium bicarbonate or lime solution; Polymerization: Not pertinent; Inhibitor of Polymerization: Not pertinent.

Safety Profile

Poison by ingestion, inhalation, and intraperitoneal routes. Moderately toxic by skin contact. Human systemic effects by inhalation: conjunctiva irritation and respiratory effects. Corrosive to skin, eyes, and mucous membranes. Very dangerous fire hazard when exposed to heat sources, sparks, flame, or oxidzers. Reacts with water or steam to produce toxic and corrosive fumes. When heated to decomposition it emits toxic fumes of Cl-, methyl chloroformate, and phosgene.

Synthesis

Methyl chloroformate prepared by reacting methyl alcohol with phosgene.A side product (methyl carbonate) could be formed if the temperature is not kept rather low and phosgene is not used in excess:To a reaction flask fitted with a dropping-funnel, a tube to introduce the gaseous phosgene and an exit tube a 10 ml of methyl chloroformate is placed. The reaction flask is cooled to 0° C and the current of phosgene containing no chlorine is bubbled in. About one-third of reaction flask is filled with methanol from the dropping-funnel all at once. When the phosgene gas is no longer being absorbed additional portion of a fresh methanol is added to the reaction mixture. As soon as the reaction is complete, methyl chloroformate is transferred to a separatory funnel containing cold water. The heavier layer which separates from the aqueous layer is washed twice with cold water, dried over calcium chloride and fractionally distilled. The fraction passing over between 69-72 °C is collected. The yield of methyl chloroformate is about 70% of theory.The war gases chemistry and analysis, by M. Sartory, 102, 1939.

Potential Exposure

Used in synthesis of pharmaceuticals; herbicides, plastics and other organic chemicals; as a solvent in the photographic industry; as a chemical intermediate in the production of other chemicals. In WWI it was used as military tear-producing warfare agent.

Shipping

UN1238 Methyl chloroformate, Hazard class: 6.1; Labels: 6.1-Poison Inhalation Hazard, 3-Flammable liquid, 8-Corrosive material Inhalation Hazard Zone A

Incompatibilities

May form explosive mixture with air. Violent reaction with alkali metals; ethers. Incompatible with strong acids; strong bases; alcohols, oxidizers, dimethylsulfoxide; dimethyl formamide. Contact with water or moisture produces corrosive and poisonous hydrogen chloride gas, methanol and carbon monoxide. Corrodes metals in the presence of moisture. Attacks some plastics, rubber and coatings.

Waste Disposal

Consult with environmental regulatory agencies for guidance on acceptable disposal practices. Generators of waste containing this contaminant (≥100 kg/mo) must conform to EPA regulations governing storage, transportation, treatment, and waste disposal

InChI:InChI=1/C2H3ClO2/c1-5-2(3)4/h1H3

Upstream product

• 67-56-1 methanol 
• 75-44-5 phosgene 
• 101970-86-9 methyl 1,1,1-trichloromethyl carbonate 
• 97925-35-4 chlorocarbonic acid pentachloroethyl ester 
• 98020-90-7 bis(trichloromethyl) oxalate 
• 20524-84-9 trichloromethyl ether 
• 107-31-3 Methyl formate 
• 624-91-9 methyl nitrite 
• 201230-82-2 carbon monoxide 
• 6135-29-1 trichloromethyl trichloroacetate 
• 1067-52-3 tributyltin methoxide 
• 7732-18-5 water 
• 7782-50-5 chlorine 
• 94-36-0 dibenzoyl peroxide 

Downstream Products

• 13989-86-1 2-chloroethylcarbamic acid methyl ester 
• 1796-27-6 piperidine-1-carboxylic acid methyl ester 
• 3164-00-9 β-methoxycarbonyloxy-chalcone 
• 90145-35-0 2,2-Dibenzoylessigsaeure-methylester 
• 6288-11-5 2-methoxycarbonyloxy-propionic acid methyl ester 
• 854890-30-5 [2-(2-methyl-[1,3]dioxolan-2-yl)-ethyl]-carbamic acid methyl ester 
• 6269-23-4 methyl (pyridin-2-yl)carbamate 
• 98134-95-3 carbimazole 
• 28953-24-4 2-(methoxycarbonylamino)benzo[d]thiazole 
• 76076-09-0 (6-methyl-benzothiazol-2-yl)-carbamic acid methyl ester 
• 58663-62-0 benzothiazol-2-yl-methyl-carbamic acid methyl ester 
• 109473-83-8 [4-(2-morpholino-ethoxy)-phenyl]-carbamic acid methyl ester; hydrochloride 

Relevant academic research and scientific papers

Synthesis of N-trifluoromethyl amides from carboxylic acids

Found in biomolecules, pharmaceuticals, and agrochemicals, amide-containing molecules are ubiquitous in nature, and their derivatization represents a significant methodological goal in fluorine chemistry. Trifluoromethyl amides have emerged as important functional groups frequently found in pharmaceutical compounds. To date, there is no strategy for synthesizing N-trifluoromethyl amides from abundant organic carboxylic acid derivatives, which are ideal starting materials in amide synthesis. Here, we report the synthesis of N-trifluoromethyl amides from carboxylic acid halides and esters under mild conditions via isothiocyanates in the presence of silver fluoride at room temperature. Through this strategy, isothiocyanates are desulfurized with AgF, and then the formed derivative is acylated to afford N-trifluoromethyl amides, including previously inaccessible structures. This method shows broad scope, provides a platform for rapidly generating N-trifluoromethyl amides by virtue of the diversity and availability of both reaction partners, and should find application in the modification of advanced intermediates.

Photolytic Activation of Late-Transition-Metal-Carbon Bonds and Their Reactivity toward Oxygen

The photolytic activation of palladium(II) and platinum(II) complexes [M(BPI)(R)] (R = alkyl, aryl) featuring the 1,3-bis(2-pyridylimino)isoindole (BPI) ligand has been investigated in various solvents. In the absence of oxygen, the formation of chloro complexes [M(BPI)Cl] is observed in chlorinated solvents, most likely due to the photolytic degradation of the solvent and formation of HCl. The reactivity of the complexes toward oxygen has been studied both experimentally and computationally. Excitation by UV irradiation (365 nm) of the metal complexes [Pt(BPI)Me] and [Pd(BPI)Me] leads to distortion of the square-planar coordination geometry in the excited triplet state and a change in the electronic structure of the complexes that allows the interaction with oxygen. TD-DFT computational studies suggest that, in the case of palladium, the Pd(III) superoxide intermediate [Pd(BPI)(κ1-O2)Me] is formed and, in the case of platinum, the Pt(IV) peroxide intermediate [Pt(BPI)(κ2-O2)Me]. For alkyl complexes where metal-carbon bonds are sufficiently weak, the photoactivation leads to the insertion of oxygen into the metal-carbon bond to generate alkylperoxo complexes: for example [Pd(BPI)OOMe], which has been isolated and structurally characterized. For stronger M-C(aryl) bonds, the reaction of [Pt(BPI)Ph] with O2 and light results in a Pt(IV) complex, tentatively assigned as the peroxo complex [Pt(BPI)(κ2-O2)Ph], which in chlorinated solvents reacts further to give [Pt(BPI)Cl2Ph], which has been isolated and characterized by scXRD. In addition to the facilitation of oxygen insertion reactions, UV irradiation can also affect the reactivity of other components in the reaction mixture, such as the solvent or other reaction products, which can result in further reactions. Labeling studies using [Pt(BPI)(CD3)] in chloroform have shown that photolytic reactions with oxygen involve degradation of the solvent.

Photo-on-Demand Synthesis of Chloroformates with a Chloroform Solution Containing an Alcohol and Its One-Pot Conversion to Carbonates and Carbamates

Chloroformates are key reagents for synthesizing carbonates and carbamates. The present study reports a novel photo-on-demand in situ synthesis of chloroformates with a CHCl3 solution containing a primary alkyl alcohol. It further allowed the one-pot synthesis of carbonates and carbamates through subsequent addition of alcohols or amines, respectively.

Discovery of (3-Benzyl-5-hydroxyphenyl)carbamates as new antitubercular agents with potent in vitro and in vivo efficacy

A series of 3-amino-5-benzylphenol derivatives were designed and synthesized. Among them, (3-benzyl-5-hydroxyphenyl)carbamates were found to exert good inhibitory activity against M. tuberculosis H37Ra, H37Rv and clinically isolated multidrug-resistant M. tuberculosis strains (MIC = 0.625-6.25 μg/mL). The privileged compounds 3i and 3l showed moderate cytotoxicity against cell line A549. Compound 3l also exhibited potent in vivo inhibitory activity on a mouse infection model via the oral administration. The results demonstrated 3-hydroxyphenylcarbamates as a class of new antitubercular agents with good potential.

Hepatitis C virus inhibitors, and pharmaceutical compositions and application thereof

The invention provides hepatitis C virus inhibitors, and pharmaceutical compositions and an application thereof, wherein the hepatitis C virus inhibitors are compounds represented by the formula (I), or crystal forms, pharmaceutically acceptable salts, hydrates or solvates thereof. The compounds have better inhibitory activity of a hepatitis C virus protein NS5A, have better pharmacodynamic/pharmacokinetic properties, have good applicability and high safety, can be used for preparing drugs for treatment of hepatitis C virus infection, and have good prospects for market development.

Photocatalysis of chloroform decomposition by the hexachlororuthenate(IV) ion

Dissolved hexachlororuthenate(IV) effectively catalyzes the photodecomposition of chloroform to hydrogen chloride and phosgene under near-UV (λ > 345 nm) irradiation, whereby RuCl62- is not itself photocatalytically active, but is photochemically transformed into a species that is active, possibly RuCl5(CHCl3)-. Conversion to a photoactive species during irradiation is consistent with the acceleration of the decomposition rate during the early stages and with the apparent inverse dependence of the decomposition rate on the initial concentration of RuCl62-. The displacement of Cl - by CHCl3 in the coordination sphere to create the photoactive species is consistent with the retardation of photodecomposition by both Cl- and H2O. The much smaller photodecomposition rate in CDCl3 suggests that C-H bond dissociation occurs during the primary photochemical event, which is also consistent with the presence of a CHCl3 molecule in the first coordination sphere. In the presence of RuCl62-, chloroform decomposes under near-UV irradiation to phosgene and hydrogen chloride. The photoactive species is suggested to be RuCl5(CHCl3) -.

SAR development of lysine-based irreversible inhibitors of transglutaminase 2 for huntington's disease

We report a series of irreversible transglutaminase 2 inhibitors starting from a known lysine dipeptide bearing an acrylamide warhead. We established new SARs resulting in compounds demonstrating improved potency and better physical and calculated properties. Transglutaminase selectivity profiling and in vitro ADME properties of selected compounds are also reported.

CARBONIC ACID ESTER AND MAGNETIC RECORDING MEDIUM

A carbonic acid ester is provided that is represented by the formula below and has a melting point of no greater than 0° C. (In the formula, R1 and R2 independently denote a saturated hydrocarbon group, R1 is a branched chain, and R2 is a straight or branched chain). There is also provided a magnetic recording medium that includes a non-magnetic support and, above the support, at least one magnetic layer including a ferromagnetic powder dispersed in a binder, the magnetic layer including the carbonic acid ester. Furthermore, there is provided a magnetic recording medium including a support and, above the support, a non-magnetic layer including a non-magnetic powder dispersed in a binder, and above the non-magnetic layer, at least one magnetic layer including a ferromagnetic powder dispersed in a binder, the non-magnetic layer and/or the magnetic layer including the carbonic acid ester.

CARBONATES OF FENICOL ANTIBIOTICS

Novel fenicol compounds having useful properties as antibiotic prodrugs, are provided, together with methods of making and using these new compounds.

A novel class of potent influenza virus inhibitors: Polysubstituted acylthiourea and its fused heterocycle derivatives

A series of polysubstituted and fused heterocycle derivatives of acylthiourea was prepared and the biological activity against influenza virus was evaluated. Of the analogues that demonstrated IC50s 0.1 μM, acylthiourea derivatives 16 and 50 were further investigated as candidates with the most potential for future development. The SAR of these compounds are discussed and they represent a novel class of highly potent and selective inhibitors of influenza virus.