Chloromethyl methyl ether (CMME) is a
compound with formula CH
3OCH
2Cl. A colorless liquid, it is a
chloroalkyl ether. It is used as an
alkylating agent
Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a carbanion, or a carbene (or their equivalents). Alkylating agents are reagents for effecting ...
. In
organic synthesis
Organic synthesis is a special branch of chemical synthesis and is concerned with the intentional construction of organic compounds. Organic molecules are often more complex than inorganic compounds, and their synthesis has developed into one o ...
, it is used for introducing the
methoxymethyl ether (MOM)
protecting group
A protecting group or protective group is introduced into a molecule by chemical modification of a functional group to obtain chemoselectivity in a subsequent chemical reaction. It plays an important role in multistep organic synthesis.
In man ...
, and is thus often called MOM-Cl or MOM chloride. It also finds application as a chloromethylating agent in some variants of the
Blanc chloromethylation
The Blanc chloromethylation (also called the Blanc reaction) is the chemical reaction of aromatic rings with formaldehyde and hydrogen chloride to form chloromethyl arenes. The reaction is catalyzed by Lewis acids such as zinc chloride. The ...
.
Preparation
A convenient synthesis of chloromethyl methyl ether ''in situ'' involves the reaction of
dimethoxymethane and acetyl chloride in the presence of a Lewis acid catalyst
This route affords a
methyl acetate
Methyl acetate, also known as MeOAc, acetic acid methyl ester or methyl ethanoate, is a carboxylate ester with the formula CH3COOCH3. It is a flammable liquid with a characteristically pleasant smell reminiscent of some glues and nail polish remo ...
solution of chloromethyl methyl ether of high purity. A similar method, using a high-boiling acyl chloride, can be used to prepare pure, dimethoxymethane being the only contaminant. In contrast, the classical procedure reported in ''
Organic Syntheses'' employing
formaldehyde
Formaldehyde ( , ) ( systematic name methanal) is a naturally occurring organic compound with the formula and structure . The pure compound is a pungent, colourless gas that polymerises spontaneously into paraformaldehyde (refer to section ...
,
methanol, and
hydrogen chloride
The compound hydrogen chloride has the chemical formula and as such is a hydrogen halide. At room temperature, it is a colourless gas, which forms white fumes of hydrochloric acid upon contact with atmospheric water vapor. Hydrogen chloride g ...
yields material significantly contaminated with the dangerous
bis(chloromethyl) ether and requires
fractional distillation
Fractional distillation is the separation of a mixture into its component parts, or fractions. Chemical compounds are separated by heating them to a temperature at which one or more fractions of the mixture will vaporize. It uses distillation to ...
.
Safety
The amount of time required to destroy residual chloromethyl methyl ether using various standard aqueous quench solutions (ammonium chloride solution, water, and sodium carbonate solution) has been measured. In all cases, a solution of chloromethyl methyl ether in toluene/methyl acetate was destroyed (to within detection limit) after vigorous stirring with the quench solution for 15 minutes.
CMME is a known human
carcinogen
A carcinogen is any substance, radionuclide, or radiation that promotes carcinogenesis (the formation of cancer). This may be due to the ability to damage the genome or to the disruption of cellular metabolic processes. Several radioactive subst ...
. Chronic exposure can increase the incidence of
respiratory
The respiratory system (also respiratory apparatus, ventilatory system) is a biological system consisting of specific organs and structures used for gas exchange in animals and plants. The anatomy and physiology that make this happen varies gre ...
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
s, including
small cell carcinoma
Small-cell carcinoma is a type of highly malignant cancer that most commonly arises within the lung, although it can occasionally arise in other body sites, such as the cervix, prostate, and gastrointestinal tract. Compared to non-small cell ca ...
.
[Chloromethyl methyl ether]
. U.S. Environmental Protection Agency, Integrated Risk Information System. 7 March 2011. Accessed 3 May 2011. It is one of 13 chemicals regulated by the
Occupational Safety and Health Administration
The Occupational Safety and Health Administration'' (OSHA ) is a large regulatory agency of the United States Department of Labor that originally had federal visitorial powers to inspect and examine workplaces. Congress established the agenc ...
despite not having an established
permissible exposure limit
The permissible exposure limit (PEL or OSHA PEL) is a legal limit in the United States for exposure of an employee to a chemical substance or physical agent such as high level noise. Permissible exposure limits are established by the Occupational ...
.
[NIOSH Pocket Guide to Chemical Hazards]
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It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S. Emergency Planning and Community Right-to-Know Act
The Emergency Planning and Community Right-to-Know Act of 1986 is a United States federal law passed by the 99th United States Congress located at Title 42, Chapter 116 of the U.S. Code, concerned with emergency response preparedness.
On Octo ...
(42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.[http://laws-lois.justice.gc.ca/PDF/SOR-2012-285.pdf {{Bare URL PDF, date=March 2022]
References
Reagents for organic chemistry
Alkylating agents
Protecting groups
Organochlorides
Ethers
IARC Group 1 carcinogens