· Acetyl Bromide
· (MW 122.95)
(bromoacylation of carbonyl compounds;1 selective O-acetylation;3,4 addition to carbon-nitrogen double bond of unsubstituted cyclic imidates;6 coupling with vinylcopper reagents;7 hydrohalogenation of alkynes8)
Physical Data: mp -96 °C; bp 75-77 °C; colorless liquid; d 1.663 g cm-3.
Solubility: sol organic solvents; reacts violently with water, alcohols, and oxidizing agents.
Handling, Storage, and Precautions: corrosive and lachrymator; keep bottle tightly closed. Reacts violently with water. Store under nitrogen. Store in a cool dry place.
The reaction of aldehydes and ketones with acetyl bromide to prepare a-bromoalkyl esters has been known in the literature since the early 1900s.2 The low yields are a consequence of the fact that the reaction is an equilibrium and that the reactants can revert to starting materials if heated in the presence of the Lewis acid catalyst.1 Yields are favorable in the case of aliphatic, a,b-unsaturated, and aromatic aldehydes and aliphatic ketones (eq 1). Highest yields are obtained at low temperatures (-10 °C).1
Addition of acetyl bromide to a solution of 5-methyluridine in acetonitrile heated at reflux gave the bromo ester in 97% yield (eq 2).3
Hydroxy groups can be selectively acetylated in the presence of primary and secondary amino groups with acetyl bromide and Trifluoroacetic Acid. Diacetylapomorphine (1) was obtained in 70% yield using this system.4 Acetylation of apomorphine with Acetic Anhydride and base or acid afforded the ring-opened product (2).5
Acetyl bromide reacts with unsubstituted cyclic imidates to yield ring-opened products (eq 3).6 (Z)-Alkenyllithium cuprate reagents are very reactive towards acetyl bromide and give (Z)-a,b-enones in moderate yield (eq 4).7 Terminal alkynes which usually undergo slow addition of HBr in solution afford bromides in good yield on treatment with acetyl bromide over alumina (eq 5).8
- 1. (a) Neuenschwander, M.; Bilger, P.; Christen, K.; Iseli, R.; Kyburz, R.; Muhle, H. HCA 1978, 61, 2047. (b) ibid., 1978, 61, 2059. (c) ibid., 1978, 61, 2165. (d) Bigler, P.; Muhle, H.; Neuenschwander, M. S 1978, 593.
- 2. (a) Descude, M. BSF 1902, 867. (b) Ulich, L. H.; Adams, R. JACS 1921, 43, 660. (c) French, H. E.; Adams, R. JACS 1921, 43, 651.
- 3. Mansuri, M. M.; Starrett, J. E.; Wos, J. A.; Tortolani, D. R.; Brodfuehrer, P. R.; Howell, H. G.; Martin, J. C. JOC 1989, 54, 4780.
- 4. Borgman, R. J.; McPhillips, J. J.; Stitzel, R. E.; Goodman, I. J. JMC 1973, 16, 630.
- 5. Borgman, R. J.; Smith, R. V.; Keiser, J. E. S 1975, 249.
- 6. Kobayashi, S., Isobe, M., Saegusa, T. BCJ 1982, 55, 1921.
- 7. Jabri, N., Alexakis, A., Normant, J. F. T 1986, 42, 1369.
- 8. Kropp, P. J.; Daus, K. A.; Crawford, S. D.; Tubergen, M. W.; Kepler, K. D.; Craig S. L.; Wilson, V. P. JACS 1990, 112, 7433.
John C. Sih
The Upjohn Company, Kalamazoo, MI, USA
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