2-Bromo-2-methylpropionyl Bromide1

[20769-85-1]  · C4H6Br2O  · 2-Bromo-2-methylpropionyl Bromide  · (MW 229.90)

(useful reagent for the preparation of ketenes,1,2 amides,3,4 alkynic ketones,5 and macrocyclic amides6,7)

Physical Data: bp 162-164 °C; d 1.860 g cm-3.

Solubility: sol polar aprotic and nonpolar solvents; reacts with protic solvents.

Form Supplied in: colorless liquid, widely available.

Handling, Storage, and Precautions: should be handled in a dry atmosphere. Hydrogen bromide is evolved upon exposure to water and protic solvents. A well-ventilated fume hood should be used when handling this compound. Adequate skin and eye protection should also be worn.

Preparation of Ketenes.

Treatment of 2-bromo-2-methylpropionyl bromide with Zinc turnings in ethyl acetate affords dimethylketene in 46-54% yield (eq 1).1 The dimethylketene is obtained as a 9-10% solution in ethyl acetate by distillation of the reaction mixture at 300 mmHg. Treatment of 2-bromo-2-methylpropionyl bromide with propargyl alcohol affords the propargyl ester, which is converted to the ketene acid upon treatment with zinc dust in benzene (eq 2).2 The transformation of the propargyl ester to the ketene acid occurs by formation of the zinc enolate, followed by a [3,3]-sigmatropic rearrangement.2a

Preparation of Amides.

A variety of aromatic and aliphatic amines react with 2-bromo-2-methylpropionyl bromide to afford the corresponding amides.3 These amides have then been used in a variety of subsequent reactions that take advantage of the bromocarbon functionality. For example, treatment of 6-amino-1,3-dihydro-2H-indol-2-one with 2-bromo-2-methylpropionyl bromide afforded the intermediate acyl derivative, which was cyclized to 5,7-dihydro-3,3-dimethylbenzo[1,2-b:5,4-b]dipyrrole-2,6-(1H,3H)-dione upon treatment with Aluminum Chloride (eq 3).4

Preparation of Alkynic Ketones.

Treatment of phenyl(trimethylsilyl)acetylene with 2-bromo-2-methylpropionyl bromide in the presence of aluminum chloride afforded 4-bromo-4-methyl-1-phenylpent-1-yn-3-one (eq 4).5 This alkynic ketone could also be made from phenylacetylene and 2-bromo-2-methylpropionyl bromide using dichlorobis(triphenylphosphine)palladium(II)-Copper(I) Iodide as catalyst. This alkynic ketone served as a key precursor to the natural product bullatenone.

Preparation of Macrocyclic Amides.

Treatment of ethylenediamine with 2-bromo-2-methylpropionyl bromide in chloroform in the presence of Pyridine afforded N,N-ethylenebis(2-bromoisobutyramide) (eq 5), which served as a precursor to macrocyclic nitrogen-sulfur compounds.6 These macrocycles were then used as ligands for transition metals. Several other macrocyclic nitrogen ligands have been prepared using 2-bromo-2-methylpropionyl bromide.7

1. Smith, C. W.; Norton, D. G. OSC 1963, 4, 348.
2. (a) Baldwin, J. E.; Walker, J. A. CC 1973, 117. (b) Luedtke, A. E.; Timberlake, J. W. JOC 1985, 50, 268.
3. For examples, see: Coutts, I. G. C.; Southcott, M. R. JCS(P1) 1990, 767. Maran, F.; Fabrizio, M.; D'Angeli, F.; Vianello, E. T 1988, 44, 2351. Maran, F.; Viahello, E.; D'Angeli, F.; Cavicchioni, G.; Vecchiati, G. JCS(P2) 1987, 33. Bergman, J.; Brynolf, A.; Vuorinen, E. T 1986, 13, 3689. Holmes, T. J., Jr.; Lawton, R. G. JOC 1983, 48, 3146. Scrimin, P.; D'Angeli, F.; Baioni, V.; Cavicchioni, G. JCR(S) 1983, 248.
4. von der Saal, W.; Hölck, J.-P.; Kampe, W.; Mertens, A.; Müller-Beckmann, B. JMC 1989, 32, 1481.
5. Jackson, R. F. W.; Raphael, R. A. JCS(P1) 1984, 535; TL 1983, 24, 2117.
6. Krüger, H.-J.; Peng, G.; Holm, R. H. IC 1991, 30, 734.
7. Collins, T. J.; Kostka, K. L.; Uffelman, E. S.; Weinberger, T. L. IC 1991, 30, 4204. Collins, T. J.; Powell, R. D.; Slebodnick, C.; Uffelman, E. S. JACS 1991, 113, 8419.

Charles H. Winter

Wayne State University, Detroit, MI, USA

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