Reagent Friday: NBS (N-Bromo Succinimide)
Last updated: March 2nd, 2020 |
N-Bromosuccinimide (NBS) As A Reagent In Organic Chemistry
In a blatant plug for the Reagent Guide, each Friday I profile a different reagent that is commonly encountered in Org 1/ Org 2.
N-Bromosuccinimide Is A More Convenient Alternative To Bromine (Br2)
If you’ve ever had the “pleasure” of working with bromine (Br2), you’ll know that this dense orange liquid is a pain in the butt for two reasons. First of all, it fumes like a bastard. Once you open the bottle, orange fumes start spewing everywhere, and if you haven’t put the bottle deep into the fume hood, you will soon be savoring the unforgettable aroma of Br2 (mixed with HBr) in your nostrils. Secondly, it’s extremely dense (d=3.19) and therefore drops of it tend to fall from whatever you’re using to dispense it with, Jackson Pollock style, leaving a little trail of violently fuming orange puddles behind. [Edit: Thank you to commenter Dr. Fred Schreiber for pointing out that this behavior is due to the high vapor pressure of Br2, not the density.]
In contrast, NBS (N-bromo succinimide) is a gleaming white crystalline solid and easy as pie to work with. But don’t be deceived. It packs a punch. It will do many of the same reactions as bromine – attached to the electron-withdrawing nitrogen of succinimide, the bromine has a partial positive charge and is therefore electrophilic.
NBS As A Reagent For Allylic Bromination
Allylic bromination is the replacement of a hydrogen on a carbon adjacent to a double bond (or aromatic ring, in which case it’s called benzylic bromination). NBS is used as a substitute for Br2 in these cases since Br2 tends to react with double bonds to form dibromides. The advantage of NBS is that it provides a low-level concentration of Br2, and bromination of the double bond doesn’t compete as much.
Allylic Bromination With NBS: How It Works
Once Br2 is formed, the reaction proceeds much like other free-radical halogenation reactions: homolytic cleavage of the Br2 with light or head (initiation), followed by abstraction of the allylic H (propagation step #1) and subsequent reaction of this radical with another equivalent of Br2 to give the desired product. The remaining Br radical then reacts with another equivalent of the hydrocarbon in this chain reaction until the limiting reagent is consumed.
NBS As A Reagent For Bromohydrin Formation From Alkenes
NBS can also serve as a replacement for Br2 in formation of halohydrins.
Recall that alkenes react with Br2 to form “bromonium ions“, which are 3-atom rings with a positive charge on the bromine. Well, NBS will also form bromonium ions with alkenes. When water (or an alcohol) is used as a solvent, it will attack the bromonium ion, resulting in formation of the halohydrin. Note that the stereochemistry is always “trans“.
There are tons of other uses for NBS beyond what you see in Org 1/Org 2, of course, but those are the basics.
(Advanced) References and Further Reading
- Bromohydrin formation in dimethyl sulfoxide
David R. Dalton, Ved P. Dutta, and Daniel G. Jones
Journal of the American Chemical Society 1968, 90 (20), 5498-5501
The synthesis of halohydrins is commonly taught to undergraduates studying organic chemistry. Bromohydrins can be conveniently formed from alkenes using NBS in moist DMSO.The allylic or benzylic bromination of hydrocarbons using NBS and a radical initiator is also known as the Wohl-Ziegler reaction.
- Brominations with N-Bromosuccinimide and Related Compounds. The Wohl-Ziegler Reaction.
Chemical Reviews 1948, 43 (2), 271-317
An old review on this reaction by noted chemist Carl Djerassi, whose major contribution to global health was the development of norethindrone – the first female contraceptive.
- N-Bromosuccinimide. III. Stereochemical Course of Benzylic Bromination
W. J. Dauben Jr. and Layton L. McCoy
Journal of the American Chemical Society 1959, 81 (20), 5404-5409
A mechanistic study on the stereochemistry of benzylic bromination. By observing the formation of racemic benzylic bromides from prochiral substrates, the intermediacy of radicals in this reaction is further strengthened.The same references from allylic bromination can be repurposed here:
- Mechanisms of Benzylic Bromination
Glen A. Russell, Charles. DeBoer, and Kathleen M. Desmond
Journal of the American Chemical Society 1963 85 (3), 365-366
Benzylic bromination follows the same mechanism as allylic bromination, as this paper explains.NBS is a convenient reagent for free-radical bromination, and the following papers are mechanistic studies involving NBS:
- The Mechanism of Benzylic Bromination with N-Bromosuccinimide
R. E. Pearson and J. C. Martin
Journal of the American Chemical Society 1963 85 (3), 354-355
These papers by Prof J. C. Martin (UIUC) were early in his career, before he did the work that he is most well-known for (studies on ‘hypervalent’ molecules, including the development of the ‘Dess-Martin Periodinane’).
- The Identity of the Chain-Carrying Species in Brominations with N-Bromosuccinimide: Selectivity of Substituted N-Bromosuccinimides toward Substituted Toluenes
R. E. Pearson and J. C. Martin
Journal of the American Chemical Society 1963, 85 (20), 3142-3146
- N-bromosuccinimide. Mechanisms of allylic bromination and related reactions
J. H. Incremona and James Cullen Martin
Journal of the American Chemical Society 1970, 92 (3), 627-634
- Succinimidyl radical as a chain carrier. Mechanism of allylic bromination
J. C. Day, M. J. Lindstrom, and P. S. Skell
Journal of the American Chemical Society 1974, 96 (17), 5616-5617
- Radical Bromination of Cyclohexene in CCl4 by Bromine: Addition versus Substitution
D. W. McMillen and John B. Grutzner
The Journal of Organic Chemistry 1994, 59 (16), 4516-4528
This paper describes careful kinetic studies that demonstrate that a low concentration of Br2 (such as that provided by impure NBS) will favor radical substitution over a polar addition reaction.
F. L. Greenwood, M. D. Kellert, and J. Sedlak
Org. Synth. Vol. 38, p.8 (1958).
A reliable procedure for allylic bromination with NBS in Organic Syntheses.