[75-64-9]  · C4H11N  · t-Butylamine  · (MW 73.14)

(reagent for preparation of hindered imines and amides;1 reagent for selective cleavage of methyl phosphate esters; solvent for metal reductions and couplings; solvent for selective bromination of phenols; hindered base; equivalent of ammonia)

Physical Data: bp 45 °C, d 0.698 g cm-3.

Solubility: broadly sol organic solvents.

Form Supplied in: mobile liquid; widely available.

Purification: distillation from sodium hydroxide.

Handling, Storage, and Precautions: as a volatile amine, handling should always be done in a fume hood. Store in tightly capped bottles at rt in ventilated cabinets.

Hindered Imines.

Numerous procedures are available for the preparation of N-t-butyl imines utilizing various dehydrating methods. Aldehydes condense readily without solvent or catalyst, or with sieves as dehydrating agent.1,3,5,6 Ketones require a catalyst such as Titanium(IV) Chloride,4 Potassium Carbonate,3a or dry EtOH.2 The steric hindrance provided by the t-butyl group typically discourages reaction at the imine carbon as in the monoalkylation of ketones and aldehydes through their magnesio-imines (eq 1),3 and the cyclization of a-chloro ketimines to cyclopropanes (eq 2).4 The t-butyl group has also been an excellent substituent for the preparation of stable oxaziridines from imines (eq 3).5 The differences in the rate of reaction typically seen between aldehydes and ketones have been used to prepare t-butyl imines of the former selectively.6 Numerous examples also exist of the use of t-butyl amides for the purpose of discouraging reaction at the amide carbonyl group.7

Phosphate Ester Cleavage.

This reagent has found a unique advantage in the selective SN2 cleavage of methyl esters of phosphoric acid in the presence of ethyl esters allowing nucleotide chemists unusual flexibility (eq 4).8a Selective cleavage of a b-cyanoethyl phosphate ester has also been effected through hindered base elimination in pyridine.8b

Solvent for Metal-Catalyzed Couplings and Reductions.

Substitution of t-butylamine for ethylamine or ammonia in dissolving metal reductions is often advantageous.9 Useful advantage has been made in Cu catalyzed couplings of acetylenes and naphthols.10

Hindered Base in Eliminations.

Several examples are available of the use of the hindered amine function in eliminations.8c,11

Selective o-Bromination of Phenols.

This amine has been used to successfully act as acid scavenger in the bromination of phenols, producing only ortho products. Effective removal of HBr by precipitation of the amine salt as it is formed is crucial to the regioselectivity.12 See Bromine-t-Butylamine.

Ammonia Equivalent.

The facile acid removal of the t-butyl group in t-butyl esters has been extended in some cases to amides and amines.4,13 The typical acidic reagents for this transformation are harsher, limiting the utility. While sulfonamides are more typical as ammonia carriers, acid cleavage does allow selective production of the sulfonamide from an N-t-butyl benzenesulfonamide.13

1. Verhe, R.; De Kimpe, N.; De Buyck, L.; Schamp, N. S 1975, 455.
2. Buchi, G.; Powell, J. E., Jr. JACS 1970, 92, 3126.
3. (a) Stork, G.; Dowd, S. R. OSC 1988, 6, 526. (b) JACS 1963, 85, 2178.
4. De Kimpe, N.; Sulmon, P.; Brunet, P. JOC 1990, 55, 5777.
5. (a) Emmons, W. D. JACS 1957, 79, 5739. (b) Emmons, W. D.; Pagano, A. S. OSC 1973, 5, 191. (c) Kloc, K.; Kubicz, E.; Mochowski, J.; Syper, L. S 1987, 1084. (d) Said, S. B.; Mlochowski, J.; Skarzewski, J. LA 1990, 461.
6. (a) Zecchini, G. P.; Paradisi, M. P.; Torrini, I. T 1983, 39, 2709. (b) Paradisi, M. P.; Zecchini, G. P.; Ortar, G. TL 1980, 21, 5085.
7. (a) Rubottom, G. M.; Pichardo, J. L. SC 1973, 3, 185. (b) Bhawal, B. M.; Khanapure, S. P.; Biehl, E. R. SC 1990, 20, 3235.
8. (a) Gray, M. D. M.; Smith, D. J. H. TL 1980, 21, 859. (b) Smith, D. J. H.; Ogilvie, K. K.; Gillen, M. F. TL 1980, 21, 861. (c) Cosstick, R.; Vyle, J. S. CC 1988, 992.
9. (a) Boar, R. B.; Joukhadar, L.; McGhie, J. F.; Misra, S. C.; Barrett, A. G. M.; Barton, D. H. R.; Prokopiou, P. A. CC 1978, 68. (b) Barrett, A. G. M.; Prokopiou, P. A.; Barton, D. H. R. CC 1979, 1175. (c) JCS(P1) 1981, 1510.
10. (a) Cameron, M. D.; Bennett, G. E. JOC 1957, 22, 557. (b) Hovorka, M.; Gunterova, J.; Zavada, J. TL 1990, 31, 413.
11. (a) Matteson, D. S.; Mah, R. W. H. JOC 1963, 28, 2174. (b) Sanchez, J. P.; Parcell, R. F. JHC 1990, 27, 1601.
12. (a) Pearson, D. E.; Wysong, R. D.; Breder, C. V. JOC 1967, 32, 2358. (b) Danheiser, R. L.; Gee, S. K.; Perez, J. J. JACS 1986, 108, 806. (c) Deck, L. M.; Brazwell, E. M.; Vander Jagt, D. L.; Royer, R. E. OPP 1990, 22, 495.
13. Lombardino, J. G. JOC 1971, 36, 1843.

Lee H. Latimer

Sterling Winthrop, Collegeville, PA, USA

Copyright 1995-2000 by John Wiley & Sons, Ltd. All rights reserved.