N-Bromosuccinimide

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N-Bromosuccinimide
Identifiers
CAS number128-08-5 YesY
ChemSpider60528 YesY
ChEBICHEBI:53174 YesY
Jmol-3D imagesImage 1
Properties
Molecular formulaC4H4BrNO2
Molar mass177.98 g mol−1
AppearanceWhite solid
Density2.098 g/cm3 (solid)
Melting point

175-178 °C, 448-451 K, 347-352 °F

Boiling point

339 °C, 612 K, 642 °F

Solubility in water1.47 g / 100 mL (25 °C)
Solubility in CCl4Insoluble (25 °C)
Hazards
MSDS[1]
Main hazardsIrritant
 YesY (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references
 
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N-Bromosuccinimide
Identifiers
CAS number128-08-5 YesY
ChemSpider60528 YesY
ChEBICHEBI:53174 YesY
Jmol-3D imagesImage 1
Properties
Molecular formulaC4H4BrNO2
Molar mass177.98 g mol−1
AppearanceWhite solid
Density2.098 g/cm3 (solid)
Melting point

175-178 °C, 448-451 K, 347-352 °F

Boiling point

339 °C, 612 K, 642 °F

Solubility in water1.47 g / 100 mL (25 °C)
Solubility in CCl4Insoluble (25 °C)
Hazards
MSDS[1]
Main hazardsIrritant
 YesY (verify) (what is: YesY/N?)
Except where noted otherwise, data are given for materials in their standard state (at 25 °C, 100 kPa)
Infobox references

N-Bromosuccinimide or NBS is a chemical reagent used in radical substitution and electrophilic addition reactions in organic chemistry. NBS can be a convenient source of cationic bromine.

Preparation[edit]

NBS is commercially available. It can also be synthesized in the laboratory. To do so, sodium hydroxide and bromine are added to an ice-water solution of succinimide. The NBS product precipitates out and can be collected by filtration.[citation needed]

Crude NBS gives better yield in the Wohl-Ziegler reaction. In other cases, impure NBS (slightly yellow-colored) may give unreliable results. It can be purified by recrystallization from 90–95 °C water (10g of NBS for 100mL of water).[1]

Reactions[edit]

Addition to alkenes[edit]

NBS will react with alkenes 1 in aqueous solvents to give bromohydrins 2. The preferred conditions are the portionwise addition of NBS to a solution of the alkene in 50% aqueous DMSO, DME, THF, or tert-butanol at 0 °C.[2] Formation of a bromonium ion and immediate attack by water gives strong Markovnikov addition and anti stereochemical selectivities.[3]

Bromohydrin formation

Side reactions include the formation of α-bromo-ketones and dibromo compounds. These can be minimized by the use of freshly recrystallized NBS.

With the addition of nucleophiles, instead of water, various bifunctional alkanes can be synthesized.[4]

The bromofluorination of cyclohexene

Allylic and benzylic bromination[edit]

Standard conditions for using NBS in allylic and/or benzylic bromination involves refluxing a solution of NBS in anhydrous CCl4 with a radical initiator—usually azo-bis-isobutyronitrile (AIBN) or benzoyl peroxide—, irradiation, or both to effect radical initiation.[5][6] The allylic and benzylic radical intermediates formed during this reaction are more stable than other carbon radicals and the major products are allylic and benzylic bromides. This is also called the Wohl-Ziegler reaction.[7][8]

Allylic bromination of 2-heptene

The carbon tetrachloride must be maintained anhydrous throughout the reaction, as the presence of water may likely hydrolyze the desired product.[9] Barium carbonate is often added to maintain anhydrous and acid-free conditions.

In the above reaction, while a mixture of isomeric allylic bromide products are possible, only one is created due to the greater stability of the 4-position radical over the methyl-centered radical.

Bromination of carbonyl derivatives[edit]

NBS can α-brominate carbonyl derivatives via either a radical pathway (as above) or via acid-catalysis. For example, hexanoyl chloride 1 can be brominated in the alpha-position by NBS using acid catalysis.[10]

Alpha-bromination of hexanoyl chloride

The reaction of enolates, enol ethers, or enol acetates with NBS is the preferred method of α-bromination as it is high-yielding with few side-products.[11][12]

Bromination of aromatic derivatives[edit]

Electron-rich aromatic compounds, such as phenols, anilines, and various aromatic heterocycles,[13] can be brominated using NBS.[14][15] Using DMF as the solvent gives high levels of para-selectivity.[16]

Hofmann rearrangement[edit]

NBS, in the presence of a strong base, such as DBU, reacts with primary amides to produce a carbamate via the Hofmann rearrangement.[17]

The Hofmann rearrangement using NBS

Selective oxidation of alcohols[edit]

It is uncommon, but possible for NBS to oxidize alcohols. E. J. Corey et al. found that one can selectively oxidize secondary alcohols in the presence of primary alcohols using NBS in aqueous dimethoxyethane (DME).[18]

The selective oxidation of alcohols using NBS

Oxidative decarboxylation of amino acids[edit]

NBS electrophilically brominates the amine, which is followed by decarboxylation and release of an imine. Hydrolysis of the imine yields an aldehyde and ammonia. (c.f. with non oxidative PLP dependant decarboxylation)[citation needed]

Precautions[edit]

Although NBS is easier and safer to handle than bromine, precautions should be taken to avoid inhalation. NBS should be stored in a refrigerator. NBS will decompose over time giving off bromine. Pure NBS is white, but it is often found to be off-white or brown colored by bromine.

In general, reactions involving NBS are exothermic. Therefore, extra precautions should be taken when used on a large scale.

See also[edit]

References[edit]

  1. ^ Dauben Jr., H. J.; McCoy, L. L. (1959). "N-Bromosuccinimide. I. Allylic Bromination, a General Survey of Reaction Variables". J. Am. Chem. Soc. 81 (18): 4863–4873. doi:10.1021/ja01527a027. 
  2. ^ Hanzlik, R. P., "Selective epoxidation of terminal double bonds", Org. Synth. ; Coll. Vol. 6: 560 
  3. ^ Beger, J. (1991). "Präparative Aspekte elektrophiler Dreikomponentenreaktionen mit Alkenen". J. Prakt. Chem. 333 (5): 677–698. doi:10.1002/prac.19913330502. 
  4. ^ Haufe, G.; Alvernhe, G.; Laurent, A.; Ernet, T.; Goj, O.; Kröger, S.; Sattler, A. (2004), "Bromofluorination of alkenes", Org. Synth. ; Coll. Vol. 10: 128 
  5. ^ Carl Djerassi (1948). "Brominations with N-Bromosuccinimide and Related Compounds. The Wohl-Ziegler Reaction". Chem. Rev. 43 (2): 271–317. doi:10.1021/cr60135a004. PMID 18887958. 
  6. ^ F. L. Greenwood; M. D. Kellert; J. Sedlak (1963), "4-Bromo-2-heptene", Org. Synth. ; Coll. Vol. 4: 108 
  7. ^ A. Wohl (1919). Ber. 52: 51. 
  8. ^ Karl Ziegler, et al. (1942). Annalen der Chemie 551: 30. 
  9. ^ Binkley, R. W; Goewey, G. S; Johnston, J (1984). "Regioselective ring opening of selected benzylidene acetals. A photochemically initiated reaction for partial deprotection of carbohydrates". J. Org. Chem. 49 (6): 992. doi:10.1021/jo00180a008. 
  10. ^ Harpp, D. N.; Bao, L. Q.; Coyle, C.; Gleason, J. G.; Horovitch, S. (1988), "2-Bromohexanoyl chloride", Org. Synth. ; Coll. Vol. 6: 190 
  11. ^ Stotter, P. L.; Hill, K. A. (1973). "α-Halocarbonyl compounds. II. Position-specific preparation of α-bromoketones by bromination of lithium enolates. Position-specific introduction of α,β-unsaturation into unsymmetrical ketones". J. Org. Chem. 38 (14): 2576. doi:10.1021/jo00954a045. 
  12. ^ Lichtenthaler, F. W.; O'dea, DJ; Shapiro, GC; Patel, MB; Mcintyre, JT; Gewitz, MH; Hoegler, CT; Shapiro, JT et al. (1992). "Various Glycosyl Donors with a Ketone or Oxime Function next to the Anomeric Centre: Facile Preparation and Evaluation of their Selectivities in Glycosidations". Synthesis 1992 (9): 784–92. doi:10.1055/s-1992-34167. PMID 1839242.  More than one of |last1= and |last= specified (help); More than one of |first1= and |first= specified (help);
  13. ^ Amat, M.; Hadida, S.; Sathyanarayana, S.; Bosch, J. (1998), "Regioselective synthesis of 3-substituted indoles", Org. Synth. ; Coll. Vol. 9: 417 
  14. ^ Gilow, H. W.; Burton, D. E. (1981). "Bromination and chlorination of pyrrole and some reactive 1-substituted pyrroles". J. Org. Chem. 46 (11): 2221. doi:10.1021/jo00324a005. 
  15. ^ Brown. W. D.; Gouliaev, A. H. (2005), "Synthesis of 5-bromoisoquinoline and 5-bromo-8-nitroisoquinoline", Org. Synth. 81: 98 
  16. ^ Mitchell, R. H.; Lai, Y.H.; Williams, R. V. (1979). "N-Bromosuccinimide-dimethylformamide: a mild, selective nuclear monobromination reagent for reactive aromatic compounds". J. Org. Chem. 44 (25): 4733. doi:10.1021/jo00393a066. 
  17. ^ Keillor, J. W.; Huang, X. (2004), "Methyl carbamate formation via modified Hofmann rearrangement reactions", Org. Synth. ; Coll. Vol. 10: 549 
  18. ^ Corey, E. J.; Ishiguro, M (1979). "Total synthesis of (±)-2-isocyanopupukeanane". Tetrahedron Lett. 20 (30): 2745–2748. doi:10.1016/S0040-4039(01)86404-2. 

External links[edit]