[51-80-9]  · C5H14N2  · Bis(dimethylamino)methane  · (MW 102.18)

(precursor for the preparation or in situ generation of N,N-dimethyl(methylene)ammonium salts;2,3 used for dimethylaminomethylation of active methylene compounds,1,4 arylstannanes,5 and electron-rich heterocycles;6 useful for the preparation of a,b-unsaturated ketones7)

Alternate Names: N,N,N,N-tetramethylmethanediamine; dimethyl(dimethylamino)methylamine; formaldehyde bis(N,N-dimethylaminal).

Physical Data: bp 85 °C; d 0.749 g cm-3; fp -12 °C.

Solubility: sol H2O, ether.

Form Supplied in: colorless liquid; widely available.

Purification: dried over potassium hydroxide pellets and distilled.

Handling, Storage, and Precautions: highly flammable. Potent lachrymator. Emits toxic fumes under fire conditions. Handle with gloves in a well-ventilated fume hood. Incompatible with acids, acid chlorides, strong oxidizing agents, and carbon dioxide.

Bis(dimethylamino)methane (1) can be used for the dimethylaminomethylation of active methylene compounds. Acidic conditions such as Trifluoroacetic Acid (TFA) (eq 1)4 or Phosphoric Acid in Acetic Acid (eq 2)8 catalyze the elimination of dimethylamine from (1), resulting in the formation of N,N-dimethyl(methylene)ammonium salts. The in situ use of these salts in the Mannich reaction is usually more convenient than the direct use of the preformed N,N-dimethyl(methylene)ammonium salts, since the latter are typically hygroscopic and difficult to handle.

Acyl chlorides or Chloroiodomethane can also be used in combination with (1) to accomplish dimethylaminomethylation of activated methylene compounds (eq 3)9 and silyl enol ethers (eq 4),10 respectively. The resulting tertiary amine may in some instances be eliminated to produce the corresponding terminal alkene (eq 5).11 Reagent (1) was shown by de Solms7 to be superior to the classical Mannich base for the preparation of a,b-unsaturated ketones (eq 6).

N,N-Dimethyl(methylene)ammonium chloride and iodide can be prepared and isolated from the reaction of (1) with Acetyl Chloride (eq 7)2 or Iodotrimethylsilane (eq 8),3 respectively. However, in the reaction of (1) with Chlorotrimethylsilane, the formation of N,N-dimethyl(methylene)ammonium chloride is not observed.12 Thus in dimethylaminomethylation reactions employing (1) and TMSCl, the reactive intermediate is most likely to be the quarternary silylammonium salt (eq 9).

Dimethylaminomethylations of aryltrialkylstannanes with (1) in the presence of silyl chlorides have been reported (eq 10).5 Reagent (1) also reacts with heterocyclic compounds such as N-methylpyrroles (eq 11) and indoles (eq 12) in the presence of acetyl chloride or excess Sulfur Dioxide to provide the corresponding Mannich products.6

Related Reagents.

(Dimethylamino)methyl Methyl Ether; Dimethyl(methylene)ammonium Iodide; Formaldehyde-Dimethylamine; (Methoxymethyl)bis(trimethylsilyl)amine; N-(Methylthiomethyl)piperidine; Tris(dimethylamino)methane; Tris(formylamino)methane.

1. Kleinman, E. F. COS 1991, 2, 895.
2. Kinast, G.; Tietze, L. F. AG(E) 1976, 15, 239.
3. Bryson, T. A.; Bonitz, G. H.; Reichel, C. J.; Dardis, R. E. JOC 1980, 45, 524.
4. Gaudry, M.; Jasor, Y.; Khac, T. B. OSC 1988, 4, 474.
5. Cooper, M. S.; Fairhurst, R. A.; Heaney, H.; Papageorgiou, G.; Wilkins, R. F. T 1989, 45, 1155.
6. Eyley, S. C.; Heaney, H.; Papageorgiou, G.; Wilkins, R. F. TL 1988, 29, 2997.
7. de Solms, S. J. JOC 1976, 41, 2650.
8. Lednicer, D.; Hauser, C. R. OSC 1973, 5, 434.
9. Hester, J. B., Jr. JOC 1979, 44, 4165.
10. (a) Miyano, S.; Hokari, H.; Mori, A.; Hashimoto, H. CL 1980, 1213. (b) Miyano, S.; Hokari, H.; Hashimoto, H. BCJ 1982, 55, 534.
11. Taylor, E. C.; Shvo, Y. JOC 1968, 33, 1719.
12. Heaney, H.; Papageorgiou, G.; Wilkins, R. F. CC 1988, 1161.

Allen J. Duplantier

Pfizer Central Research, Groton, CT, USA

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