Iodomethyl Methyl Ether

ICH2OMe

[13057-19-7]  · C2H5IO  · Iodomethyl Methyl Ether  · (MW 171.97)

(reactive methoxymethylating agent for phosphorus,1 carbon,2 oxygen,3 and nitrogen4 nucleophiles; iodomethylating agent for aromatic systems5)

Alternate Name: iodomethoxymethane.

Physical Data: bp 122 °C (dec), 39 °C/20 mmHg; d 2.030 g cm-3.

Solubility: sol common organic solvents.

Form Supplied in: liquid, commercially available (stabilized with copper).

Preparative Methods: displacement of chloride from Chloromethyl Methyl Ether by iodide ion, followed by distillation of the product (eq 1);2a,2b,5b reaction of Formaldehyde or trioxane with methanol and Hydrogen Iodide (eq 2);6 reaction of methylal (Dimethoxymethane) with Iodotrimethylsilane (eq 3).1a This last route has the advantage of not using or producing highly carcinogenic materials such as chloromethyl methyl ether or Bis(chloromethyl) Ether.

Handling, Storage, and Precautions: corrosive and a lachrymator; a strong alkylating agent and as such is likely to be harmful if swallowed or absorbed through the skin. It should be handled accordingly. Use in a fume hood.

Methoxymethylations.

The addition of a methoxymethyl group to a reactive functionality is a useful process in organic chemistry. Quite often this can be carried out by using the reagents Chloromethyl Methyl Ether and Bromomethyl Methyl Ether. However, occasionally the more reactive iodomethyl methyl ether (1) has been used instead.

Reaction of (1) with Grignard reagents produces methoxymethylated compounds, e.g. (3) from (2) (eq 4), in high yield.2b

The lithium salts of vinyl carbanions can also be methoxymethylated with (1).2a Reaction with alkoxides affords the methoxymethylated ethers (MOM ethers) in good yield, e.g. (5) from (4) (eq 5).3a

The commonly used methoxymethyltriphenylphosphonium halide (6) can also be easily prepared from (1) and Triphenylphosphine in good yield (eq 6) under milder conditions than with chloromethyl methyl ether.1a

Reaction with various amines, e.g. Triethylamine or Hexamethylenetetramine, leads to the salts in good yield as expected.4 A nice use of the reagent was in the trapping of the cyclopentanone enolate (8) generated by addition of the organolithium (7) to cyclopentenone to furnish the bis-alkylated cyclopentanone (9) in fine yield. This compound was then taken on to sarkomycin (10) (eq 7).7

Iodomethylations.

Treatment of various aromatic compounds such as styrene and their derived polymers, e.g. polystyrene, with iodomethyl methyl ether (1) in the presence of a Lewis acidic metal iodide, e.g. SnI4 or Zinc Iodide, affords the iodomethyl aromatic derivatives (eq 8).5

Related Reagents.

Bromomethyl Methyl Ether; Chloromethyl Methyl Ether.


1. (a) Jung, M. E.; Mazurek, M. A.; Lim, R. M. S 1978, 588. (b) Lutsenko, I. F.; Prishchenko, A. A.; Livantsov, M. V. DOK 1987, 295, 884.
2. (a) Boehme, H.; Stammberger, W. AP 1972, 305, 392. (b) Lapkin, I. I.; Lapkina, O. M. ZOB 1952, 22, 1602 (CA 1953, 47, 9293f). (c) Malm, L.; Summers, L. JACS 1951, 73, 362.
3. (a) Priepke, H.; Brückner, R. CB 1990, 123, 153. (b) Mihelich, E. D. U.S. Patent 4 345 984 (CA 1983, 98, 125 739).
4. (a) Maccio, I. An. Farm. Bioquím. 1942, 13, 112 (CA 1943, 37, 38 798). (b) Ewins, A. J. BJ 1914, 8, 371.
5. (a) Rogozhin, S. V.; Davankov, V. A.; Korshak, V. V. IZV 1966, 1498 (CA 1966, 65, 17 057). (b) Rogozhin, S. V.; Korshak, V. V.; Davankov, V. A.; Maslova, L. A. Vysokomol. Soedin. 1966, 8, 1275 (CA 1967, 66, 65 989). (c) Ergozhin, E. E.; Rafikov, S. R.; Mukhitdinova, B. A. Izv. Akad. Nauk-Kaz. SSR, Ser. Khim. 1969, 19, 49 (CA 1970, 72, 67 619).
6. (a) Henry, L. Bull. Acad. Roy. Belg. 1893, 25, 439; CB 1893, 26, 933. (b) Gauthier, M. D. Ann. Chim. Phys. 1909, 16, 289. (c) See also Ref. 2c.
7. Otera, J.; Niibo, Y.; Nozaki, H. JOC 1989, 54, 5003.

Michael E. Jung

University of California, Los Angeles, CA, USA



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