Tris(dimethylamino)methane1
(Me2N)3CH
[5762-56-1] · C7H19N3 · Tris(dimethylamino)methane · (MW 145.29)
(reactive aminomethylenating reagent (formylating reagent) for CH2- and NH2-acidic compounds; can serve as a source for bis(dimethylamino)carbene)
Alternate Names: TDAM; N,N,N�,N�,N��,N��-hexamethylmethanetriamine.
Physical Data: bp 42-43 °C/12 mmHg; n20D = 1.4360.
Solubility: miscible with nonpolar aprotic, water-free solvents; reacts with protic solvents such as water, alcohols, and even aprotic, weak CH-acidic solvents such as acetone and acetonitrile on heating.
Form Supplied in: colorless to light yellow liquid; strong amine smell.
Analysis of Reagent Purity: 1H NMR spectrum of a neat sample.
Preparative Methods: can be prepared by reaction of lithium dimethylamide with either N,N,N�,N�-tetramethylformamidinium salts2 or bis(dimethylamino)acetonitrile (eqs 1 and 2).3 The lithium dimethylamide solution can be prepared from lithium, dimethylamine, and naphthalene in dry THF.4 Lithium dimethylamide can be replaced by sodium dimethylamide,2 which is accessible in situ from Sodium Hydride, dimethylamine, and catalytic amounts (~20%) of Trimethyl Borate.5
In the reaction of tetramethylformamidinium chloride with triphenylphosphonium ylides, TDAM is formed as a byproduct.6 TDAM is also obtained as a byproduct in the synthesis of alkanethiobis(dimethylamino)methanes from sodium alkanethiolates and N,N,N�,N�-tetramethylformamidinium methylsulfate or from aminal esters and alkanethiols by disproportionation of the primary products.7 Triethyl Orthoformate reacts with lithium dimethylamide (prepared in situ from lithium and dimethylamine) in HMPA to give TDAM.8 In an equilibrium reaction, DMF acetals react with dimethylamine to give TDAM.9 This reaction can be used on a preparative scale, if the dimethylamine is introduced at about 100 °C in the presence of 2,4,6-trimethylphenol as catalyst.10 The transamination of bis(dimethylamino)alkoxymethanes with excess dimethylamine affords TDAM.11 TDAM is produced in good yields in the reaction of tetrakis(dimethylamino)titanium with N,N-Dimethylformamide in ether (eq 3).12
Good yields of TDAM can be obtained by reduction of N,N,N�,N�,N��,N��-hexamethylguanidinium chloride with a mixture of sodium hydride and Sodium Bis(2-methoxyethoxy)aluminum Hydride (75%)13 or by a mixture of sodium hydride and trimethyl borate (eq 4).5
Handling, Storage, and Precautions: should be handled and used with strict exclusion of atmospheric moisture. The product should be stored in a tightly sealed container under a dry nitrogen or argon atmosphere in a refrigerator or freezer. Use in a fume hood.
Conductivity measurements4 demonstrate that tris(dimethylamino)methane dissociates into dimethylamide anions and N,N,N�,N�-tetramethylformamidinium cations (eq 5). This equilibrium enables an understanding of the important reactions of TDAM. Thus XH2-acidic compounds are deprotonated by the reagent; if the anions thus formed are small and relatively unstabilized, they combine with formamidinium ions to give adducts which eliminate dimethylamine to form a dimethylaminomethylene group. This mechanism has been confirmed by 1H NMR investigations.14 If the first step involves large, well-stabilized anions, the reaction stops at the stage of ion pairs.
Reactions.
Even weak CH-acidic compounds such as ketones,15-22 nitriles and dinitriles,21,23 lactones,24-29 2- or 4-nitro-1-alkylbenzenes,21,30,31 fluorene and xanthene,14 4-methylpyridine,21 lactams,15 N-substituted a-amino esters,32 and methylenediphosphonates33 react according to this scheme. The condensation products contain a masked aldehyde function and are frequently used as difunctional intermediates. Two applications are photooxidation to a-dicarbonyl compounds15,25,28 and condensation with suitable difunctional compounds to form heterocyclic rings, including pyrimidines,16-18,26 pyrazoles,17,19 isoxazoles,20 1,4-dihydropyridines,32 and indoles.30,31 Eqs 6-11 show some examples.
If elevated temperatures are required for reactions, it should be noted that tris(dimethylamino)methane decomposes to tetrakis(dimethylamino)ethylene at 150-190 °C (eq 12).34
Tertiary XH-acidic compounds, such as phenylacetylene35 and a-diazo carbonyl compounds36 undergo bis(dimethylamino)methylation with this reagent, whereas a,a-disubstituted aldehydes are converted to enamines (eqs 13-15).37
Reaction with Pentacarbonyliron affords a carbamoyltetracarbonyliron anion complex (eq 16).38,39
Tris(dimethylamino)methane can also serve as a strong base in deprotonation of organic compounds.40,41 The anions thus formed can be used in further reactions (e.g. eq 17).41
In the rhodium-catalyzed reaction of TDAM with CO and a silyl hydride, a substituted 1,2-diamino-3-silyloxypropane derivative is formed (eq 18).42
Prolonged heating of selenium and TDAM affords N,N,N�,N�-tetramethylselenourea;43 bis(dimethylamino)carbene (or an equivalent species) may be an intermediate in this reaction (eq 19).
t-Butoxybis(dimethylamino)methane; N,N-Dimethylformamide; N,N-Dimethylformamide Diethyl Acetal; Tris(formylamino)methane.
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2. Bredereck, H.; Effenberger, F.; Brendle, T.; Muffler, H. CB 1968, 101, 1885.
3. Kantlehner, W.; Maier, T.; Speh, P. S 1979, 342.
4. Ref. 1g, p 180.
5. Kantlehner, W. Unpublished results; Regele, C. Diploma Thesis, FH Aalen, 1986.
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11. Bredereck, H.; Simchen, G.; Schenck, H.-U. CB 1968, 101, 3058. Ref. 1g, p 182.
12. Weingarten, H.; White, W. A. JOC 1966, 31, 2874.
13. Kantlehner, W.; Speh, P.; Bräuner H.-J. S 1983, 905.
14. Weingarten, H.; Edelmann, N. K. JOC 1967, 32, 3293.
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22. Hart, T. W.; Vacher, B. TL 1992, 33, 7215.
23. Kantlehner, W.; Mergen, W.; Haug, E.; Speh, P.; Kapassakalidis, J. J.; Bräuner, H.-J. LA 1985, 1804.
24. Martin, S. F.; Moore, D. R. TL 1976, 4459.
25. Collins, P. M.; Overend, W. G.; Shing, T. CC 1981, 1139.
26. Sato, T.; Watanabe, M.; Noyori, R. CL 1980, 6, 679.
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30. Kruse, L. I. H 1981, 16, 1119.
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34. Bredereck, H.; Effenberger, F.; Bredereck, H. J. AG 1966, 78, 984; AG(E) 1966, 5, 971.
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36. Regitz, M.; Schoder, W. S 1985, 178.
37. Hauthal, H. G.; Schied, D. ZC 1969, 9, 62.
38. Schmetzer, J.; Daub, J.; Fischer, P. AG 1975, 87, 489; AG(E) 1975, 14, 487.
39. Daub, J.; Hasenhündl, A.; Krenkler, K. P.; Schmetzer, J. LA 1980, 997.
40. Bredereck, H.; Simchen, G.; Porkert, H. CB 1970, 103, 245.
41. Leimgruber, W.; Wick, A. E. U.S. Patent 3 922 285, 1975 (CA 1976, 84, 121 439t).
42. Ikeda, S.; Chatani, N.; Murai, S. OM 1992, 11, 3494.
43. Hauber, M. PhD Thesis, University of Stuttgart, 1989; p 60.
Willi Kantlehner
Universität Stuttgart, Germany