51-75-2

Basic information

• Product Name: Chlormethine
• Synonyms: Dichloramine;Bis-(2-chloroethyl)methylamine;chlormethine;N,N-BIS-(2-CHLOROETHYL)METHYLAMINE;Mustine;MECHLOROETHAMINE;DI(2-CHLOROETHYL)METHYLAMINE;N-METHYL-BIS(2-CHLOROETHYL)AMINE
• CAS NO: 51-75-2
• Molecular Formula: C₅H₁₁Cl₂N
• Molecular Weight: 156.05
• EINECS: 200-120-5
• Mol File: 51-75-2.mol
• Article Data: 16

Chemical Properties

• Melting Point: -60°
• Boiling Point: bp18 87°; bp10 75°; bp5 64°; bp2 59°
• Flash Point: 20.5 °C
• Appearance: mobile liquid
• Density: d425 1.118
• Vapor Density: 0.17 mm at 25°C
• Vapor Pressure: 3.66mmHg at 25°C
• Refractive Index: 1.5500 (estimate)
• PKA: 6.40±0.30(Predicted)
• CAS DataBase Reference: Chlormethine(CAS DataBase Reference)
• NIST Chemistry Reference: Chlormethine(51-75-2)
• EPA Substance Registry System: Chlormethine(51-75-2)

Safety Data

• RIDADR: 2810
• HazardClass: 6.1(a)
• PackingGroup: II
• Hazardous Substances Data: 51-75-2(Hazardous Substances Data)

Usage

Description

Chlormethine, also known as HN-2, is a nitrogen mustard compound with a fishy odor and lachrymatory properties. It is a pale yellow, oily, mobile liquid at room temperature and is similar in structure to mustard gas, with the sulfur replaced by an amino nitrogen. Chlormethine was initially produced as a chemical warfare agent during the 1920s and 1930s but has since been used sparingly in chemotherapy and as an antineoplastic agent.

Uses

Used in Anticancer Applications:
Chlormethine is used as an antineoplastic agent for the treatment of cancer. It has been employed in chemotherapy, particularly against solid malignancies, due to its ability to interfere with cell division and DNA synthesis in cancer cells.
Used in Chemical Warfare:
Chlormethine, under the military designation HN-2, was formerly used as a gas warfare agent. However, its use in this context is now highly restricted, and there are no current records of its use for this purpose.
Used in Pharmaceutical Industry:
Chlormethine is used in the pharmaceutical industry under the brand name Mustargen (Ovation) as a drug for the treatment of cancer. Its application in this industry is focused on its antineoplastic properties, which make it a valuable compound in the fight against various types of cancer.

Production Methods

The nitrogen mustards are tertiary amines in which the halogen atom and the amine portion have reactivities similar to those of alkyl halides and alkyl amines. They are oily liquids that have limited water solubility but form readily soluble hydrochlorides. They are prepared by the action of thionyl chloride on the appropriate alkanolamine. Many of the actions of the nitrogen mustards resemble those of ethyleneimine derivatives because they are transformed in aqueous solutions into the highly reactive ethylenimonium intermediates: these ions can readily react with a variety of organic compounds in vitro, especially with amino, sulfhydro, and carboxyl groups of proteins and phosphate groups in nucleic acid, and therefore can alkylate biologically important macromolecules.

Reactivity Profile

Chlormethine is a chlorinated amine. Amines are chemical bases. They neutralize acids to form salts plus water. These acid-base reactions are exothermic. The amount of heat that is evolved per mole of amine in a neutralization is largely independent of the strength of the amine as a base. Amines may be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents, such as hydrides.

Hazard

Strong irritant to tissues, lachrymatory. Probable carcinogen.

Health Hazard

Toxic doses as low as 400 mg/kg have been reported in humans. Blood clots may occur at site of intravenous injection and tissue damage if outside vein. Powerful vesicant (causes blisters) when it contacts skin, mucous membranes, or eyes. Delayed toxicity -- missed menstrual periods, alopecia (hair loss), hearing loss, tinnitus (ringing in ears), jaundice, impaired spermatogenesis and germinal aplasia, swelling, and hypersensitivity. May damage fetus in pregnant women.

Fire Hazard

Undiluted liquid decomposes on standing.

Safety Profile

Confirmed human carcinogenproducing skin tumors by skin contact. Experimentalcarcinogenic, tumorigenic, and neoplastigenic data. Adeadly poison by inhalation, ingestion, skin contact, andmost other routes. Experimental teratogenic andreproductive eff

Potential Exposure

Drug used in treatment of cancer. Exposure to nitrogen mustard damages the eyes, skin, and respiratory tract and suppresses the immune system. Although the nitrogen mustards cause cellular changes within minutes of contact, the onset of pain and other symptoms is delayed. Exposure to large amounts can be fatal. Sulfur mustards were formerly used as a gas warfare agent. Nitrogen mustards have not previously been used in warfare

Shipping

UN2810 Toxic liquids, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required. Military driver shall be given full and complete information regarding shipment and conditions in case of emergency. AR 50-6 deals specifically with the shipment of chemical agents. Shipments of agent will be escorted in accordance with AR 740-32

Incompatibilities

HN-2 is not stable except as dry crystals. Polymerization of HN-2 results in components that present an explosion hazard in open air. Avoid contact or contamination with oxidizers e.g., nitrates, oxidizing acids; chlorine bleaches pool chlorine); which may result in ignition. Unstable in the presence of light and heat and forms dimers at temperatures above 50C. Corrosive to ferrous alloys beginning @ 65C. Polymerizes slowly, so munitions would be effective for several years. Heated to decomposition emits hydrogen chloride and nitrogen oxide. Contact with metals may evolve flammable hydrogen gas. Note: Chlorinating agents destroy nitrogen mustards. Dry chlorinated lime and chloramines with a high content of active chlorine vigorously chlorinate nitrogen mustards to the carbon chain, giving low toxicity products. In the presence of water this interaction proceeds less actively. They are rapidly oxidized by peracids in aqueous solution at weakly alkaline pH. In acid solution the oxidation is much slower.An amine and a chemical base: will neutralize acids to form salts plus water with an exothermic reaction. May be incompatible with isocyanates, halogenated organics, peroxides, phenols (acidic), epoxides, anhydrides, and acid halides. Flammable gaseous hydrogen is generated by amines in combination with strong reducing agents such as hydrides, nitrides, alkali metals, and sulfides

Waste Disposal

It is inappropriate and possibly dangerous to the environment to dispose of expired or waste drugs and pharmaceuticals by flushing them down the toilet or discarding them to the trash. Household quantities of expired or waste pharmaceuticals may be mixed with wet cat litter or coffee grounds, double-bagged in plastic, discard in trash. Larger quantities shall carefully take into consideration applicable DEA, EPA, and FDA regulations. If possible return the pharmaceutical to the manufacturer for proper disposal being careful to properly label and securely package the material. Alternatively, the waste pharmaceutical shall be labeled, securely packaged, and transported by a state licensed medical waste contractor to dispose by burial in a licensed hazardous or toxic waste landfill or incinerator

InChI:InChI=1/C5H11Cl2N/c1-4(6)8(3)5(2)7/h4-5H,1-3H3

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Relevant articles and documents

Synthesis and cytotoxicity of pyridine and quinoline oxorhenium(V) complexes with tridentate (NS2, S3)/monodentate (S) coordination

New oxorhenium complexes with tridentate 3-thia- and 3-methylazapentane-1, 5-dithiolate and monodentate pyridine and quinoline derivatives have been synthesized. As a result of investigation of biological activity a high cytotoxicity was found for the synthesized complexes in relation to tumor cells. The specificity of the 2-pyridylthiolato[3-(N-methyl)azapentane-1,5-dithiolato] oxorhenium(V) cytotoxic action towards cells of mouse hepatoma MG-22A on a background of low acute toxicity was established.

Utilisation of new NiSNS pincer complexes in paraffin oxidation

Two series of closely related SNS pincer ligands (L) were synthesised with the major structural variation on the nitrogen backbone containing either the methyl [L = (RSCH2CH2)2NMe: where R = Me (1), Et (2), Bu (3)] or the phenyl [L = (RSCH2CH2)2NPh: where R = Me (4), Et (5), Cy (6)] functional group. When ligands 1–3 were complexed to Ni by reaction with Ni(DME)Cl2 (DME = dimethoxyethane), they respectively yielded three new cationic dimeric [LNi(μ-Cl)3NiL]+ complexes (7–9), whilst ligands 4–6 on reaction with Ni(PPh3)2Br2 respectively yielded neutral mononuclear (LNiBr2) complexes 10–12. All the new compounds were characterised by IR, HRMS, elemental analysis and in addition, single crystal X-ray diffraction for complexes 9–12. X-ray structural data of 9 revealed an unusual three chlorido-bridged Ni dimer with the SNS ligand coordinated in a facial binding mode to the two pseudo-octahedral Ni centres. Molecular structures of complexes 10, 11 and 12 each displayed five-coordinate distorted trigonal bipyramidal geometry around the nickel(II) metal centres. When utilised as catalysts in the tert-butyl hydroperoxide oxidation of n-octane, all the complexes showed activity to mainly products of internal carbon activation (octanones and secondary octanols) with 11 as the most active (10% total substrate to oxygenates yield), whereas 10 was the least active, but most selective towards alcohols (alcohol/ketone = 2.13).

THERAPEUTIC FOR HEPATIC CANCER

A novel pharmaceutical composition for treating or preventing hepatocellular carcinoma and a method of treatment are provided. A pharmaceutical composition for treating or preventing liver cancer is obtained by combining a chemotherapeutic agent with an anti-glypican 3 antibody. Also disclosed is a pharmaceutical composition for treating or preventing liver cancer which comprises as an active ingredient an anti-glypican 3 antibody for use in combination with a chemotherapeutic agent, or which comprises as an active ingredient a chemotherapeutic agent for use in combination with an anti-glypican 3 antibody. Using the chemotherapeutic agent and the anti-glypican 3 antibody in combination yields better therapeutic effects than using the chemotherapeutic agent alone, and mitigates side effects that arise from liver cancer treatment with the chemotherapeutic agent.