Chloroalkyl ether

Chemical structure of chloromethyl methyl ether.

Chloroalkyl ethers are a class of organic compounds with the general structure R-O-(CH₂)_n-Cl, characterized as an ether connected to a chloromethyl group via an alkane chain.

Chloromethyl methyl ether (CMME) is an ether with the formula CH₃OCH₂Cl. It is used as an alkylating agent and industrial solvent to manufacture dodecylbenzyl chloride, water repellents, ion-exchange resins, polymers, and as a chloromethylation reagent. It is a known human carcinogen.^[1] In organic synthesis the compound is used for the introduction of the methoxymethyl (MOM) protecting group.

Closely related compounds of industrial importance are bis(chloromethyl) ether (BCME) (closely related to chemical weapon sulfur mustard)^[2] and benzyl chloromethyl ether (BOMCl).

Chloromethyl ether	R		Molar mass	CAS number	Boiling point °C
Benzyl chloromethyl ether	Benzyl		156.61	3587-60-8	102°C @ 14 mmHg (1.9 kPa)
Chloromethyl methyl ether	Methyl		80.51	107-30-2	55-57
Bis(chloromethyl) ether			114.96	542-88-1	106
tert-Butyl chloromethyl ether	Butyl		124.5
Methoxyethyl chloromethyl ether			124.57	3970-21-6	50-52°C @ 13 mmHg (1.7 kPa)
Dichloromethyl methyl ether			114.96	4885-02-3	82 - 85.5°C
Representative chloroalkyl ethers[3]

MOM ethers

Methyl chloromethyl ether (often abbreviated MOMCl) is used as a protecting group for alcohols. The product formed is a MOM ether. A base such as N,N-diisopropylethylamine is a requirement.

The MOM group can be removed by application of dilute acid.

An example is the protection of a phenol group:^[4]

With a benzyl group the protective group becomes a BOM-ether. See also the closely related methylthiomethyl ethers.

A t-butyl group can also be used. The chloride is prepared from Methyl tert-butyl ether using a photochemical chlorination.^[5]

With a methoxyethoxyl group the protective group becomes a MEM-ether. This ether is much more stable than the MOM ether to hydrolysis.

References

1. ↑ Bis(chloromethyl) Ether and Technical-Grade Chloromethyl Methyl Ether CAS Nos. 542-88-1 and 107-30-2, Report on carcinogens, Eleventh edition
2. ↑ Bis(Chloromethyl) ether Safety Data Sheet, Division of Occupational Health and Safety, US National Institutes of Health
3. ↑ http://www.sigmaaldrich.com
4. ↑ Enantioselective total synthesis of (2)-heliannuol A Hidetoshi Kishuku, Mitsuru Shindo and Kozo Shishido Chem. Commun., 2003, 350–351 Article link
5. ↑ Protection chemistry Professor Tore Benneche, University of Oslo