(Dimethylamino)methyl Methyl Ether1

(1; R = Me)

[62393-45-7]  · C4H11NO  · (Dimethylamino)methyl Methyl Ether  · (MW 89.14) (2; R = Bu)

[56275-84-4]  · C7H17NO  · Butyl (Dimethylamino)methyl Ether  · (MW 131.22)

(precursor for N,N-dimethyl(methylene)ammonium salts;2,3 useful for the in situ dimethylaminomethylation of silyl enol ethers to produce b-(N,N-dimethylamino) ketones (Mannich bases)4,5)

Physical Data: (1) bp 67 °C/760 mmHg; (2) bp 128 °C/756 mmHg.

Solubility: sol H2O, acetonitrile.

Preparative Methods: amino ethers (1)3 and (2)6 are prepared from a mixture of dimethylamine (0.5 mol), alcohol (1 mol), and Potassium Carbonate (0.6 mol) at 0 °C. Paraformaldehyde is added after a few min, and the mixture is stirred overnight at room temperature. The product is purified by filtration followed by distillation to give a colorless liquid.

Handling, Storage, and Precautions: handle with gloves in a well-ventilated fume hood. Incompatible with acids and acid chlorides. Readily decomposes in water in the presence of acid.

General Discussion.

The mechanism of the acid-catalyzed hydrolysis of (2), which involves the formation of an iminium intermediate, has been studied in detail.6 N,N-Dimethyl(methylene)ammonium salts are readily obtained by the reaction of (1) with acid halides (eq 1) or Methyltrichlorosilane (eq 2).3 The latter method may be used in situ for dimethylaminomethylation of silyl enol ethers to give b-(N,N-dimethylamino) ketones in good yield (eq 3).4

In a similar manner, (2) reacts with silyl enol ethers in the presence of either Iodotrimethylsilane or Trimethylsilyl Trifluoromethanesulfonate to provide the Mannich reaction product (eq 4).5 However, in the reaction of (2) with Chlorotrimethylsilane the effective intermediate is believed to be an oxonium salt as there is no evidence of the formation of an iminium salt. It is interesting to note that the use of Bis(dimethylamino)methane in the place of (2) in the above reaction does not proceed smoothly.

Terminal alkynes have also been converted in excellent yields into Mannich bases by reaction with (2) instead of formaldehyde and dimethylamine (eq 5).7

Related Reagents.

Bis(dimethylamino)methane; t-Butoxybis(dimethylamino)methane; Dimethyl(methylene)ammonium Iodide; Formaldehyde-Dimethylamine; (Methoxymethyl)bis(trimethylsilyl)amine; N-(Methylthiomethyl)piperidine.

1. Kleinman, E. F. COS 1991, 2, 901.
2. Bohme, H.; Sickmuller, A. CB 1977, 110, 208.
3. Rochin, C.; Babot, O.; Dunogues, J.; Duboudin, F. S 1986, 228.
4. Rochin, C.; Babot, O.; Dunogues, J.; Duboubin, F. S 1986, 667.
5. Hosomi, A.; Iijima, S.; Sakurai, H. TL 1982, 23, 547.
6. Stewart, T. D.; Bradley, W. E. JACS 1932, 54, 4172.
7. Epsztein, R.; Le Goff, N. TL 1985, 26, 3203.

Allen J. Duplantier

Pfizer Central Research, Groton, CT, USA

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