Springe direkt zu Inhalt

Methoxymethylchloride (MOM-Cl; Chloromethyl-methylether)

Methoxymethylchloride is used to introduce the MOM-protecting group. The compound is known to be very carcinogenic for human beeings, where it is still a question if present traces of bis(chloromethyl)ether are the reason of the carcinogenic potential or are only enhancing the carcinogenic effect. (See details). The compound has a very low boiling point of 59 °C and is therefore very volatile.

Methoxymethylchloride is not commercially available and has therefore to be prepared by the users. The 100 years old traditional synthesis using hydrogen chloride, formaldehyde and methanol gives significant amounts of bis(chloromethyl)ether as a by-product which cannot be completely removed by distillation. If it is necessary to use methoxymethylchloride it is better to use a modern synthesis which will not yield bis(chloromethyl)ether as a by-product, for example by using acid chlorides and dimethoxymethane as starting compounds. See

  • R.J. Linderman, M. Jaber, B.D.Griedel J. Org. Chem 59,6499-6500(1994)
  • M. Reggelin, S.Doerr Synlett 1117(2004)

Even pure methoxymethylchloride develops slowly bis(chlormethyl)ether if it is left standing alone.

Substitutes

  • (2-Methoxyethoxy)-methylchloride (MEM-Cl) is also carcinogenic. There is no reason to think oneself safe because there is only rare information about the compound available. Since the compound has so far only be used in small scale reactions in scientific labs no official body had the focus on the hazardous potential. But there are two sure advantages. The compound has a high boilng point (50 - 52 °C / 13 mm) und it is commercially available.
  • (2-Chloromethoxyethyl)-trimethylsilane (SEM-Cl) is not carcinogenic. This compound is also commercially available, but the price is high (ca 40 €/g).

In a complex synthetic problem customised protecting groups are needed. General hints for a substitution are therefore not possible. Careful search of the literature is needed. (for example T.W. Greene, P.G.M. Wuts, Protective Groups in Organic Synthesis, Whiley)