Chloromethyl ethyl ether is a compound that’s used as an intermediate in organic synthesis for the preparation of various chemicals. It can be used in the production of polymers or copolymers as a monomer or as a part of the reaction process. In the pharmaceutical industry, it may be used as a building block for the synthesis of certain pharmaceutical compounds. Another application is in the production of various agrochemicals like weedicides.
What is Chloromethyl Ethyl Ether?
Chloromethyl ethyl ether is a trifluoroacetic acid derivative that is used as a solvent. It appears as a colorless liquid, and it is slightly denser than water and insoluble in it. It is particularly resistant to hydrolysis by acids. It reacts with radiation and forms a highly reactive hydroxyl radical. The biological properties of chloromethyl ethyl ether are poorly understood; however, it has been shown to bind with receptors on cells and inhibit protein synthesis. It is represented by the molecular formula C3H7OCl. The chemical structure of chloromethyl ethyl ether is shown below:
Source: PubChem
How is Chloromethyl Ethyl Ether Produced?
The most common method of production of chloromethyl ethyl ether is the reaction of hydrochloric acid, ethanol, and formaldehyde to produce chloromethyl ether. The problem with this method is that it requires hydrochloric acid, making production costs high.
Another method involves using spent phosphorus trichloride and industrial alcohol to produce chloromethyl ether by formalin reaction. This process leads to the production of large quantities of phosphorus-containing wastewater after the phosphorus trichloride hydrolysis, and after-treatment is complex, increasing the production cost.
A lower-cost method that improves the compound’s output and purity involves using hydrogen chloride as a by-product of the production of methyl Isocyanate. This replaces the hydrochloric acid from the previous process. Through thermal degradation, followed by condensation of methyl amino formyl chloride, we get methyl isocyanate in the liquid phase and hydrogen chloride in the gas phase.
Industrial Uses of Chloromethyl Ethyl Ether
As mentioned, chloromethyl ethyl ether can be used for various applications. Here are a few of its most common industrial uses.
Chloromethyl Ethyl Ether as Alkylating Agent
Alkylation agents are highly reactive drugs that bind to certain chemical groups like phosphate, amino, sulfhydryl, hydroxyl, and imidazole groups, commonly found in nucleic acids, changing the DNA and RNA of cells. Both chloromethyl ethyl ether and chloromethyl methyl ether are known to be excellent alkylation agents. Due to their carcinogenic, mutagenic effects, however, their therapeutic use is restricted.
Chloromethyl Ethyl Ether as a Solvent
Ethyl ethers are well-known solvents that can be used in various chemical processes. Chloromethyl ethyl ether is widely used for bromine, iodine, most fatty and resinous substances, volatile oils, pure rubber, and certain vegetable alkaloids.
Chloromethyl Ethyl Ether as an Intermediate
Chloromethyl Ethyl Ether can be used as an intermediate in various reactions. It can be used to prepare: 6-Benzyl-1-(ethoxymethyl)-5-iodopyridine-2,4(1H,3H)-dione, a key intermediate in the preparation of MKC-442 analog which is a derivative of 1-[(2-hydroxyethoxy)- methyl]-6-(phenyl-thio) thymine (HEPT) (1). This compound was described in 1989 as a novel inhibitor of the HIV1 RT (2, 3). MKC-442 and other NNRTIs inhibit the HIV-1 RT through allosteric interactions.
It is also used as an acylation catalyst for alcohols like 1,3-bis-[(R)-1-(2-naphthyl)ethyl] imidazolium chloride while reacting with glyoxal-bis-[(R)-1-(2-naphthyl)ethyl]imine.
Properties of Chloromethyl Ethyl Ether
| Chemical Formula | C3H7ClO |
| Molecular Weight | 94.54 g/mol |
| Melting Point | -104°C |
| Boiling Point | 82°C |
| Flash Point | 19°C |
| Vapor Pressure | 85.6mmHg at 25°C |
| Appearance | Liquid |
| Specific Gravity | 1.019 |
| Color | Clear colorless to pale yellow |
| Storage Conditions | 0-6°C |
| Refractive Index | 1.4-1.405 |
Derivatives of Chloromethyl Ethyl Ether
Chloromethyl Methyl Ether
Chloromethyl methyl ether is a colorless liquid that is used as an alkylating agent in organic synthesis. It can be used as a reagent for the introduction of a methoxymethyl (MOM) protecting group by converting alcohols to methoxymethyl (MOM) ethers. It can also be used in the preparation of some methoxymethyl groups containing metal complexes coordinated with carbonyl and dipyridyl ligands. It is a key reagent in the preparation of fluorene/chloromethyl methyl ether cross-linked polymers by Friedel-Crafts polymerization.
Chloromethyl Ethyl Carbonate
Chloromethyl ethyl carbonate is a stable compound that can be recharged with a chemical reaction. It inhibits human immunodeficiency virus type 1 (HIV-1) replication in the proximal tubule cells of the kidney. The uptake of chloromethyl ethyl carbonate by proximal tubular cells is dependent on the presence of active substances, such as tenofovir, which can be found in some antiretroviral therapy drugs. This drug has also been shown to have antihypertensive properties in humans.
Bis(Chloromethyl) Ether
Bis(chloromethyl) ether is one of the chloroalkyl ethers. It is a colorless liquid organic compound with an unpleasant, suffocating odor. It can be produced industrially from paraformaldehyde and a mixture of chlorosulfonic acid and sulfuric acid. It is also produced as a by-product in the Blanc Chloromethylation reaction, formed when formaldehyde (the monomer, paraformaldehyde, or formalin) and concentrated hydrochloric acid are mixed.
Safety & Toxicity
Flammability: Chloromethyl ethyl ether is highly flammable in both liquid and vapor form. Proper safety precautions during handling are required. Avoid heat, hot surfaces, sparks, open flames, and other ignition sources.
Eye and Skin Irritant: Chloromethyl ethyl ether is classified as toxic. If inhaled or comes in contact with the skin, it may irritate or even be fatal. It can cause a burning sensation in the eyes and skin. The use of proper safety equipment is highly recommended.
Cancer Hazard: Chloromethyl ethyl ether is classified as a Group A human carcinogen. High exposure in mice, rats, and hamsters has been shown to increase incidences of lung tumors. In employment contexts, numerous cases have been documented where workers with prolonged exposure to the compound experienced incidences of lung cancer.
Toxicity Report: Chloromethyl ethyl ether is considered a neurotoxin and may cause acute solvent syndrome in workers with prolonged exposure. It is listed as a secondary hepatotoxin, which may cause severe liver damage. Additionally, it is a well-known lachrymator, which causes severe eye irritation and causes tears to flow.
Exposure Limits
| OSHA | OSHA suggests no specific exposure limit, but extreme safety precautions are recommended for the handling of this chemical due to its high toxicity and the fact that it is suspected to be a mutagen. |
| ACGIH | ACGIH suggests no specific exposure limit. Still, extreme safety precautions are recommended for the handling of this chemical due to its high toxicity and the fact that it is suspected to be a mutagen. |
Identification Numbers
| CAS Number | 3188-13-4 |
| EC Number | 221-687-5 |
| REACH Number | A registration number is not available for this substance as the substance or its uses are exempted from registration, the annual tonnage does not require registration, or the registration is envisaged for a later registration deadline. |
Fun Facts About Chloromethyl Ethyl Ether
- Chloromethyl ethyl ether is commonly used in quaternization reactions, where it can react with nucleophiles to form quaternary ammonium salts. This property makes it useful in the synthesis of certain quaternary ammonium compounds.
- Chloromethyl ethyl ether can be used to synthesize specialty chemicals with specific properties.
