[79-15-2]  · C2H4BrNO  · N-Bromoacetamide  · (MW 137.96)

(bromohydration and bromofluorination of alkenes; oxidation of alcohols)

Alternate Name: NBA.

Physical Data: mp 102-105 °C.

Solubility: sol CHCl3, H2O, acetone, THF; insol ether, hexane.

Form Supplied in: white needles; commercially available.

Preparative Method: N-bromoacetamide has been prepared by the reaction of acetamide with bromine and 50% aqueous potassium hydroxide at 0 °C.1

Purification: NBA can be recrystallized by dissolving in chloroform (10 mL g-1), adding hexane (10 mL g-1) and cooling to 0 °C. The purity of NBA may be determined by the standard bromide-thiosulfate titration method.1

Handling, Storage, and Precautions: N-bromoacetamide should be stored in the refrigerator, and protected from light and moisture to avoid decomposition. NBA is an irritating solid and precautions should be taken to avoid inhalation of the powder or contact with skin.

Bromohydration of Alkenes.

Although more expensive than N-Bromosuccinimide, N-bromoacetamide is particularly effective for the electrophilic bromination of alkenes when a milder bromination reagent is needed, or when the ease of removal of the byproduct (acetamide) provides an advantage. The standard conditions for this reaction involve addition of NBA to a solution of the alkene in aqueous acetone, dioxane, or THF mixtures at 0 °C,2 although for less reactive alkenes catalytic sulfuric acid has been added.3 More recently, NBA has been chosen for the bromohydration of particularly reactive alkenes (eqs 1 and 2)4,5 and for the synthesis of sensitive 1,2-anhydro sugars (glycal epoxides).6 The reaction of alkenes with NBA in acetic acid has also been used for the preparation of bromoacetates.7

Bromofluorination of Alkenes.

Alkenes are converted to the corresponding 1,2-bromofluorides using NBA and anhydrous HF in ether.8 This method has been especially useful for the synthesis of fluorinated steroids, fluorinated amino acids (eq 3), and other fluorine analogs of biologically important molecules.9,10

Oxidation of Alcohols.11

NBA has mild reactivity for the oxidation of alcohols in aqueous dioxane or THF at room temperature but is generally only of preparative value for the oxidation of secondary alcohols. Although the use of N-bromoacetamide and other N-bromoamides for the oxidation of alcohols has largely been displaced by chromium reagents and activated dimethyl sulfoxide reagents, the ease of handling and the unreactivity of the byproduct acetamide may favor the use of NBA in particular applications. In addition, secondary alcohols in different environments are oxidized at appreciably different rates by NBA and the selective oxidation of axial alcohols in the presence of equatorial alcohols has frequently been achieved in the steroid field.12

Related Reagents.

N-Bromoacetamide-Silver Acetate-Acetic Acid.

1. Oliveto, E. P.; Gerold, C. OSC 1963, 4, 104.
2. Reich, H.; Reichstein, T. HVA 1943, 26, 562.
3. (a) Winstein, S.; Buckles, R. E. JACS 1942, 64, 2780. (b) Fried, J.; Sabo, E. F. JACS 1953, 75, 2273.
4. (a) Grudzinski, Z.; Roberts, S. M. JCS(P1) 1975, 1767. (b) Davies, H. G.; Roberts, S. M.; Wakefield, B. J.; Winders, J. A. CC 1985, 1166.
5. Ranganathan, S.; Ranganathan, D.; Mehrotra, A. K. TL 1975, 1215.
6. Marzabadi, C. H.; Spilling, C. D. JOC 1993, 58, 3761.
7. Payne, A. N.; Roberts, S. M. JCS(P1) 1992, 2633.
8. (a) Dean, F. H.; Amin, J. H.; Pattison, F. L. M. OSC 1973, 5, 136. (b) Pattison, F. L. M.; Peters, D. A. V.; Dean, F. H. CJC 1965, 43, 1689.
9. Bowers, A.; Ibáñez, L. C.; Denot, E.; Becerra, R. JACS 1960, 82, 4001.
10. Gershon, H.; McNeil, M. W.; Bergmann, E. D. JMC 1973, 16, 1407.
11. Filler, R. CRV 1963, 63, 21.
12. Johnson, W. S.; Collins, J. C.; Pappo, R.; Rubin, M. B.; Kropp, P. J.; Johns, W. F.; Pike, J. E.; Bartmann, W. JACS 1963, 85, 1409.

Scott C. Virgil

Massachusetts Institute of Technology, Cambridge, MA, USA

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