Ace Your Next Organic Chemistry
Exam.

With these Downloadable PDF Study Guides

Our Study Guides

Organic Reagents

By James Ashenhurst

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.]

structure-of-nbs-n-bromo-succinimide

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.

There are two major reactions NBS is used for in Org 1/ Org 2: allylic bromination (the most common) and also as a replacement for Br2 in the formation of bromohydrins.

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.

most-common-use-for-nbs-is-in-allylic-bromination-and-benzylic-bromination-examples

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.

allylic-bromination-with-nbs-how-it-works

NBS As A Reagent For Bromohydrin Formation From Alkenes

NBS can also serve as a replacement for Br2 in formation of halohydrins.

common-use-for-nbs-is-formation-of-bromohydrins

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“.

formation-of-halohydrins-how-it-works

There are tons of other uses for NBS beyond what you see in Org 1/Org 2, of course, but those are the basics.

P.S. You can read about the chemistry of NBS and more than 80 other reagents in undergraduate organic chemistry in the “Organic Chemistry Reagent Guide”, available here as a downloadable PDF.


(Advanced) References and Further Reading

  1. 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
    DOI:
    10.1021/ja01022a030
    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.
  2. Brominations with N-Bromosuccinimide and Related Compounds. The Wohl-Ziegler Reaction.
    Carl Djerassi
    Chemical Reviews 1948, 43 (2), 271-317
    DOI: 10.1021/cr60135a004
    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.
  3. 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
    DOI: 10.1021/ja01529a038
    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:
  4. Mechanisms of Benzylic Bromination
    Glen A. Russell, Charles. DeBoer, and Kathleen M. Desmond
    Journal of the American Chemical Society 1963 85 (3), 365-366
    DOI: 10.1021/ja00886a040
    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:
  5. 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
    DOI:
    10.1021/ja00886a029
    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’).
  6. 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
    DOI: 10.1021/ja00903a021
  7. 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
    DOI: 10.1021/ja00706a034
  8. 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
    DOI: 10.1021/ja00824a074
  9. 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
    DOI: 10.1021/jo00095a029
    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.
  10. 4-BROMO-2-HEPTENE
    F. L. Greenwood, M. D. Kellert, and J. Sedlak
    Org. Synth. Vol. 38, p.8 (1958).
    DOI: 10.15227/orgsyn.038.0008
    A reliable procedure for allylic bromination with NBS in Organic Syntheses.

Comments

Comment section

44 thoughts on “Reagent Friday: NBS (N-Bromo Succinimide)

  1. “The advantage of Br2 is that it provides a low-level concentration of Br2″… It should read “The advantage of NBS is that it provides a low-level concentration of Br2″…

    1. When cyclohexanone reacts with NBS/CCl4 +aq KOH we get cyclopentanoic acid as final product .I found this on a test. Can you please tell me what happened here

    1. Belated to answer your question but yes, Lewis acids are compatible with NBS and make it more reactive. It can be used to brominate aromatics. Usually works best for electron rich aromatics like phenol and pyrrole. For electron poor species I’d stick with Br2 and FeBr3 or similar.

      Sorry for the late response, hope it’s helpful James

  2. When 4-methyl-hex-2-ene reacts with NBS, you get two products. How do you know which of the products is the major product? My teacher has 2-bromo-4-methyl-hex-3-ene as the major product.

    1. Hi – that’s not an easy question to answer. Often the product depends delicately on the reaction conditions, especially the temperature. I would certainly expect that the hydrogen on C-3 is abstracted first (as opposed to C-1) giving a tertiary allylic radical (vs. a primary allylic radical) but where the c-Br bond forms is hard to predict. One thing to note is that forming the C-3 C4 double bond is more substituted (more stable) than the C2-C3 double bond (less substituted, less stable) and higher temperatures would tend to favor that product.
      I don’t have a simple answer for you unfortunately. Thanks for writing, James

  3. Does the radical intermediate undergo rearrangement to form a more stable free radical (if possible) , I have read that radicals have little tendency to rearrange unlike carbocations,
    But since the radical here is in conjugation with the double bond, shouldnt there be rearrangement (because of the contribution of second canonical form)

  4. How about mono-bromination of cyclopentylphenylmethanone to (1-bromo-cyclopentyl)-phenyl-methanone ?

    Using n-bromo succinimide?

    I wanted to insert images into this post but it does not seem possible to do so.

    Thanks for your attention!

  5. regarding your statement in “NBS (N-Bromo Succinimide)”

    “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 little violently fuming orange puddles behind.” The reason for this is not density, but bromine’s high vapor pressure. Drawing it into a pipet immediately expels it because the pressure builds in the pipet. Even the warmth of your hand on a pipet filled with bromine will pressurize the pipet and expel the bromine.

  6. James,

    NBS generates a bromine radical which then abstracts the allylic Hydrogen on propene because the allylic c-h bond is the weakest c-h bond due to resonance of the resulting allylic radical.

    However, I was also taught that bromine radicals generated from hbr reacting with RO radicals (generated by homolytic cleavage of a peroxide bond) will react with the pi bond generating the 1-broom-2-propyl radical as a propagation step of antimarkovnikov addition of hbr in the presence of peroxides.

    So where do br radicals react, at the pi bond or at the allylic c—h bond?

    1. The radicals will add to the double bond, but the radical created by that (carbon-based radical) needs something to react with to continue the chain reaction. When HBr is present, it reacts with H-Br to regenerate Br• and the cycle continues. However with allylic bromination, there isn’t a source of HBr present that can continue the chain. Therefore if radical addition happens, it just reverts back to the double bond and bromine radical. In other words, addition to the double bond is a dead end.

  7. into what is nbs converted as it reacts in allylic bromination reactions?
    – i thought it would be bromine but that is incorrect. Could it be bromine radical ?

  8. Hydrogen peroxide and bromine also gives radical bromine why does only n bromo succinamide give allylic product

  9. Toluene reacted with NBS yields p-bromotoluene, o-bromotoluene, and small amounts of m-bromotoluene…in your example you show it yields the bromine bonded to the methyl in the allylic position. I conducted this reaction in lab last week and FTIR and NMR confirmed the products I listed above. Confused as to how you came to that product?

Leave a Reply

Your email address will not be published. Required fields are marked *

This site uses Akismet to reduce spam. Learn how your comment data is processed.