[77-48-5]  · C5H6Br2N2O2  · 1,3-Dibromo-5,5-dimethylhydantoin  · (MW 285.93)

(benzylic bromination of arenes; bromoperoxylation and bromofluorination of alkenes)

Alternate Names: DBH; 1,3-dibromo-5,5-dimethylimidazolidine-2,4-dione; dibromantin.

Physical Data: mp 197-199 °C (dec).

Solubility: slightly sol acetone, THF, 1,4-dioxane, H2O (hot), CCl4 (reflux).

Form Supplied in: white powder or crystals; widely available.

Analysis of Reagent Purity: determined by the standard iodide-thiosulfate titration method.

Preparative Methods: DBH has been prepared by reaction of Br2 (1 mol) with 5,5-dimethylhydantoin (0.5 mol) and NaOH (1 mol) in ice-water at 0 °C.1a 5,5-Dimethylhydantoin is widely available commercially, and can be prepared from KOCN, (NH4)2CO3, and acetone in water at 85 °C.1a After removal of water and excess reagents by distillation, the resulting solution can be used directly for the preparation of DBH. 1,3-Dibromo-5-ethyl-5-methylhydantoin has also been prepared and has the advantage of greater solubility.1b

Purification: in an efficient fume hood (caution: bromine evolution), an impure sample of DBH (40 g) is dissolved as quickly as possible in 4 L of preheated water at 90-95 °C. The solution is filtered if necessary, and the filtrate is then immediately chilled well in an ice bath to effect crystallization. After most of the aqueous portion has been decanted, the white crystals are collected by filtration through a bed of ice and washed with water. The crystals are dried in vacuo (63-70% recovery).1a

Handling, Storage, and Precautions: 1,3-dibromo-5,5-dimethylhydantoin should be stored refrigerated and protected from light and moisture to avoid decomposition. DBH is an irritating solid and precautions should be taken to avoid inhalation of the powder or contact with skin.

Benzylic Bromination.

1,3-Dibromo-5,5-dimethylhydantoin has been used frequently for the radical bromination of benzylic positions of arenes and heterocycles. Using 0.5 molar equiv of DBH in CCl4 at reflux in the presence of Dibenzoyl Peroxide, high yields of the benzylic bromide are obtained under mild conditions. The use of DBH has been found to be advantageous for the preparation of particularly acid-sensitive benzylic bromides, as shown in eqs 1 and 2.2,3 The use of NBS in the former case affords a debenzoylated product, while in the latter example, elimination of AcOH and HBr leads to the aromatized product. DBH was also found to be the most satisfactory reagent for the dehydrogenation of azlactones (eq 3).4

Electrophilic Bromination of Alkenes.

DBH is regularly substituted for N-Bromosuccinimide in industrial applications due to its low cost and high bromine content. Electrophilic brominations of alkenes often proceed in higher yield using DBH, as shown for the bromohydration of synthesis of epoxides via bromohydrins (eq 4).5 DBH is the preferred reagent for the preparation of bromohydroperoxide precursors to 1,2-dioxetanes from alkenes using Hydrogen Peroxide.6 DBH has also been found to be the most effective reagent for the bromofluorination of alkenes in combination with Hydrogen Fluoride-Pyridine complex or Silicon(IV) Fluoride (eq 5).7 Alkynes can be converted to (E)-bromofluoroalkenes with good stereoselectivity; these are suitable substrates for palladium-catalyzed coupling (eq 6).8 In an analogous sense to the use of N-Iodosuccinimide, DBH has been employed for the coupling of glycals to alcohols affording 2-bromoglycosides which can be converted to 2-deoxyglycosides.9

Electrophilic Bromination of Thioethers.

The use of DBH for the deprotection of dithioacetals and dithianes has been found to be superior to many other methods. Transacetalation of dithianes to diethyl acetals is achieved by treatment with 1 equiv of DBH in ethanol at rt.10 In addition, dithiolanes can be converted to the corresponding geminal difluoro compounds in good yield by reaction with DBH and Pyridinium Poly(hydrogen fluoride) in dichloromethane at -78 °C.11

1. (a) Orazi, O. O.; Orio, O. A. Anales Asoc. Quím. Argentina 1953, 41, 153 (CA 1954, 48, 13 634c). (b) Orazi, O. O.; Corral, R. A.; Bonafede, J. D. Anales Asoc. Quím. Argentina 1955, 43, 98 (CA 1956, 50, 10 071c).
2. Oakes, V.; Rydon, H. N.; Undheim, K. JCS 1962, 4678.
3. (a) Domínguez, D.; Ardecky, R. J.; Cava, M. P. JACS 1983, 105, 1608. (b) Ishizumi, K.; Ohashi, N.; Tanno, N. JOC 1987, 52, 4477.
4. Lott, R. S.; Breitholle, E. G.; Stammer, C. H. JOC 1980, 45, 1151.
5. (a) Coe, D. M.; Parry, D. M.; Roberts, S. M.; Storer, R. JCS(P1) 1991, 2373. (b) See also: Li, T. T.; Marx, M. CA 1984, 100, 120 584.
6. (a) Kopecky, K. R.; van de Sande, J. H.; Mumford, C. CJC 1968, 46, 25. (b) Richardson, W. H.; Stiggal-Estberg, D. L.; Chen, Z.; Baker, J. C.; Burns, D. M.; Sherman, D. G. JOC 1987, 52, 3143. (c) Landis, M. E.; Lindsey, R. L.; Watson, W. H.; Zabel, V. JOC 1980, 45, 525.
7. (a) Eddarir, S.; Mestdagh, H.; Rolando, C. TL 1991, 32, 69. (b) Shimizu, M.; Nakahara, Y.; Yoshioka, H. CC 1989, 1881. (c) Chi, D. Y.; Kiesewetter, D. O.; Katzenellenbogen, J. A.; Kilbourn, M. R.; Welch, M. J. JFC 1986, 31, 99.
8. Eddarir, S.; Mestdagh, H.; Rolando, C. TL 1991, 32, 69.
9. Tatsuta, K.; Tanaka, A.; Fujimoto, K.; Kinoshita, M.; Umezawa, S. JACS 1977, 99, 5826.
10. Muzard, M.; Portella, C. S 1992, 965.
11. Sondej, S. C.; Katzenellenbogen, J. A. JOC 1986, 51, 3508.

Scott C. Virgil

Massachusetts Institute of Technology, Cambridge, MA, USA

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