[7726-95-6]  · Br2  · Bromine-t-Butylamine  · (MW 159.81) (t-BuNH2)

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

(reagent for ortho bromination of phenols1)

Alternate Name: bromine-2-methyl-2-propylamine.

Solubility: sol toluene.

Preparative Method: prepared in situ by addition of bromine to a solution of t-butylamine in toluene at -20 to -30 °C.

Handling, Storage, and Precautions: bromine-t-butylamine is prepared in situ, and is not generally stored. No particular hazards have been reported for this reagent combination (other than the corrosivity and toxicity hazards associated with bromine and t-butylamine), but the 1:1 complex between bromine and trimethylamine has been reported2 to explode when heated in a sealed tube. This reagent should be handled in a fume hood.

Ortho Bromination of Phenols.

The combination of Bromine and t-Butylamine has been used for the selective ortho bromination of phenols.1,3 Little or no para bromination is usually observed. The yields are generally good when 2,6-dibromination is desired (eq 1)1 or when one of the ortho positions is blocked (eq 2).4

For substrates in which both ortho positions are open (eq 3),1 or for highly activated substrates (eq 4),5 it is sometimes difficult to obtain monobrominated products. In these cases less than 1 equiv of bromine has often been employed. Yields are then calculated on moles of bromine used.

It has been speculated1,6 that the source of selectivity with the Br2.t-BuNH2 reagent is due to the formation of a hypobromite intermediate which undergoes intramolecular bromine transfer.

An interesting use of the selective properties of this reagent is demonstrated in the chemoselective bromination of phenol (1) in the presence of a trisubstituted alkene to give bromide (2) in 85% yield. Compound (2) was used in a total synthesis of mycophenolic acid.7

For other reagents useful for the ortho bromination of phenols see 2,4,4,6-Tetrabromo-2,5-cyclohexadienone.

1. Pearson, D. E.; Wysong, R. D.; Breder, C. V. JOC 1967, 32, 2358.
2. Böhme, H.; Krause, W. CB 1951, 84, 170.
3. 2-Propylamine has also been used: Cresp, T. M.; Giles, R. G. F.; Sargent, M. V.; Brown, C.; Smith, D. O. JCS(P1) 1974, 2435.
4. Ishizaki, M.; Ozaki, K.; Kanemastu, A.; Isoda, T.; Hoshino, O. JOC 1993, 58, 3877.
5. Jung, K.; Koreeda, M. JOC 1989, 54, 5667.
6. Pearson, D. E.; Buehler, C. A. S 1971, 455.
7. Danheiser, R. L.; Gee, S. K.; Perez, J. J. JACS 1986, 108, 806.

Bruce L. Finkelstein

E. I. DuPont de Nemours & Co., Newark, DE, USA

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