N-Bromosuccinimide-Dimethylformamide

(NBS)

[128-08-5]  · C4H4BrNO2  · N-Bromosuccinimide-Dimethylformamide  · (MW 177.99) (DMF)

[68-12-2]  · C3H7NO  · N-Bromosuccinimide-Dimethylformamide  · (MW 73.09)

(mild selective bromination reagent1 for reactive electron-rich aromatic hydrocarbons, heterocycles, phenols, and anilines)

Alternate Name: NBS-DMF.

Physical Data: see individual entries for N-Bromosuccinimide and N,N-Dimethylformamide.

Handling, Storage, and Precautions: NBS (recrystallized from water and dried under vacuum) should be freshly dissolved in DMF (dried over molecular sieves) immediately before use. Note: use of old NBS and undried DMF may reduce yields in some cases.

Aromatic Hydrocarbons.

The main advantage of NBS-DMF is that monobromination usually occurs cleanly with 1 equiv of reagent at rt in high yields (80-98%). At least three alkyl groups must be present on a benzene ring, or two on a naphthalene ring; however, unsubstituted anthracene,1 biphenylene,2 and pyrene1 are sufficiently reactive (eqs 1-3).

Phenols and Anisoles.

Selective monobromination of a phenol1,3 is achieved, particularly if the DMF is dry (eqs 4 and 5). However, in some cases, dibromination also occurs (eq 6).4 A difference in regiochemistry was observed5 between the phenols (eq 7) and anisoles (eq 8). Anisoles, even with several methoxy groups, can also be selectively monobrominated;6-9 an example is given in eq 9.

Anilines.

These are normally rather difficult to selectively brominate without oxidation; however, several examples1,10-13 have now been reported with NBS-DMF (for example eq 10).

Five-Membered Ring Heterocycles.

Furans,14 imidazoles,15 and thiophenes16 have now been brominated with NBS-DMF. In the thiophene shown in eq 11, 1.1 equiv of NBS gives the monobromide in 56% yield, while 2.4 equiv gives the dibromide in 70% yield.

Oxidation.

Hydroquinone is oxidized by NBS-DMF to p-benzoquinone.1 It has been recently found17 that dimethyldihydropyrene also forms the quinone when >2 equiv of NBS in wet DMF are used (eq 12).

Side Products.

In general the above reactions are fairly clean, and the main side product is usually the dibromide. The mildness, selectivity, ease of use, and ready availability of both NBS and DMF makes the use of this reagent a convenient option over alternatives such as the more reactive Thallium(III) Acetate-Bromine,18 or Copper(II) Bromide,19 or bromine itself (which is often not selective).


1. Mitchell, R. H.; Lai, Y.-H.; Williams, R. V. JOC 1979, 44, 4733.
2. Cracknell, M. E.; Kabli, R. A.; McOmie, J. F. W.; Perry, D. H. JCS(P1) 1985, 115.
3. Cambie, R. C.; Palmer, B. D. AJC 1982, 35, 827.
4. Kiehlmann, E.; Van der Merwe, P. J.; Hundt, H. K. L. OPP 1983, 15, 341.
5. Outten, R. A.; Daves, Jr., G. D. JOC 1989, 54, 29.
6. Guthrie, A. E.; Semple, J. E.; Joullié, M. M. JOC 1982, 47, 2369.
7. Outten, R. A.; Daves, Jr., G. D. JOC 1987, 52, 5064.
8. Zhu, G. D.; Chen, D. H.; Huang, J. H.; Chi, C. S.; Liu, F. K. JOC 1992, 57, 2316.
9. Cambie, R. C.; Hayward, R. C.; Palmer, B. D. AJC 1982, 35, 1679.
10. Danieli, B.; Lesma, G.; Palmisano, G.; Riva, R. JCS(P1) 1987, 155.
11. Lai, Y.-H.; Peck, T.-G. AJC 1992, 45, 2067.
12. Gruber, R.; Kirsch, G.; Cagniant, D. BSF(2) 1987, 498.
13. Groenen, L. C.; Verboom, W.; Nijhuis, W. H. N.; Reinhoudt, D. N.; Hummel, G. J.; Feil, D. T 1988, 44, 4637.
14. Tanis, S. P.; Chuang, Y.-H.; Head, D. B. JOC 1988, 53, 4929.
15. Nishiwaki, T.; Kunishige, N. JCR(M) 1984, 3465.
16. Tamao, K.; Yamaguchi, X.; Shiozaki, M.; Nakagawa, Y.; Ito, Y. JACS 1992, 114, 5867.
17. Mitchell, R. H.; Jin, X. Unpublished results.
18. McKillop, A.; Bromley, D.; Taylor, E. C. JOC 1972, 37, 88.
19. Mosnaim, D.; Nonhebel, D. C. T 1969, 25, 1591.

Reginald H. Mitchell

University of Victoria, BC, Canada



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