N-Bromosuccinimide 1858933 223013149 2008-07-02T04:45:39Z 171.67.104.226 {{Chembox new | ImageFileL1 = N-Bromosuccinimide Structure.png | ImageSizeL1 = 100px | ImageFileR1 = N-bromosuccinimide-3D-vdW.png | ImageSizeR1 = 120px | IUPACName = 1-Bromo-2,5-pyrolidinedione | OtherNames = N-bromosuccinimide; NBS | Section1 = {{Chembox Identifiers | CASNo = 128-08-5 | PubChem = | SMILES = O=C(CC1)N(Br)C1=O }} | Section2 = {{Chembox Properties | Formula = C<sub>4</sub>H<sub>4</sub>BrNO<sub>2</sub> | MolarMass = 177.98 g/mol | Appearance = White solid | Density = 2.098 g/cm3 (solid) | MeltingPt = 175 - 178 &deg;C | BoilingPt = | Solubility = 1.47 g / 100 mL (25 °C) | SolubleOther = Insoluble (25°C) | Solvent = CCl4 }} | Section3 = {{Chembox Hazards | ExternalMSDS = [http://www.jtbaker.com/msds/englishhtml/b5332.htm] | MainHazards = Irritant | FlashPt = | Autoignition = }} }} '''''N''-Bromosuccinimide''' or '''NBS''' is a [[chemical reagent]] which is used in [[radical substitution]] and [[electrophilic addition]] [[chemical reaction|reactions]] in [[organic chemistry]]. NBS can be considered a convenient source of molecular [[bromine]]. == Chemistry == ===Addition to alkenes=== NBS will react with alkenes '''1''' in aqueous solvents to give [[Halohydrin formation reaction|bromohydrins]] '''2'''. The preferred conditions are the portionwise addition of NBS to a solution of the alkene in 50% aqueous [[Dimethyl sulfoxide|DMSO]], [[dimethoxyethane|DME]], [[tetrahydrofuran|THF]], or [[Tert-Butanol|''tert''-butanol]] at 0°C.<ref>Hanzlik, R. P. ''[[Organic Syntheses]]'', Coll. Vol. 6, p.560 (1988); Vol. 56, p.112 (1977). ([http://www.orgsyn.org/orgsyn/prep.asp?prep=cv6p0560 Article])</ref> Formation of a [[bromonium ion]] and immediate attack by water gives strong [[Markovnikov's rule|Markovnikov addition]] and ''anti'' stereochemical selectivities.<ref>Beger, J. ''J. Prakt. Chem.'' '''1991''', ''333(5)'', 677-698.</ref> :[[Image:NBS Bromohydrin Formation Scheme.png|250px|Bromohydrin formation]] Side reactions include the formation of α-bromo-ketones and dibromo compounds. These can be minimized by the use of freshly [[recrystallize]]d NBS. With the addition of [[nucleophile]]s, instead of [[water (molecule)|water]], various bifunctional alkanes can be synthesized.<ref>Haufe, G.; Alvernhe, G.; Laurent, A.; Ernet, T.; Goj, O.; Kröger, S.; Sattler, A. ''[[Organic Syntheses]]'', Coll. Vol. 10, p.128 (2004); Vol. 76, p.159 (1999). ([http://www.orgsyn.org/orgsyn/prep.asp?prep=v76p0159 Article])</ref> :[[Image:NBS Fluorination.png|250px|The bromofluorination of cyclohexene]] ===Allylic and benzylic bromination=== Standard conditions for using NBS in allylic and/or benzylic [[bromination]] involves refluxing a solution of NBS in [[anhydrous]] [[carbon tetrachloride|CCl<sub>4</sub>]] with a radical initiator, usually azo-''bis''-isobutyronitrile (AIBN), [[benzoyl peroxide]], irradiation, or both to effect [[radical (chemistry)|radical]] [[initiation (chemistry)|initiation]].<ref>[[Carl Djerassi|Djerassi, C.]]; ''[[Chem. Rev.]]'' '''1948''', ''43'', 271.</ref><ref>Greenwood, F. L.; Kellert, M. D.; Sedlak, J. ''[[Organic Syntheses]]'', Coll. Vol. 4, p.108 (1963); Vol. 38, p.8 (1958). ([http://www.orgsyn.org/orgsyn/prep.asp?prep=cv4p0108 Article])</ref> 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]].<ref>Wohl, A. ''[[Ber.]]'' '''1919''', ''52'', 51.</ref><ref>[[Karl Ziegler|Ziegler, K.]]; ''et al.'' ''Ann.'' '''1942''', ''551'', 30.</ref> :[[Image:NBS Allylic Bromination Scheme.png|350px|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.<ref>Binkley, R. W.; Goewey, G. S.; Johnston, J; ''[[J. Org. Chem.]]'' '''1984''', ''49'', 992.</ref> [[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=== 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.<ref>Harpp, D. N.; Bao, L. Q.; Coyle, C.; Gleason, J. G.; Horovitch, S. ''[[Organic Syntheses]]'', Coll. Vol. 6, p.190 (1988); Vol. 55, p.27 (1976). ([http://www.orgsyn.org/orgsyn/prep.asp?prep=cv6p0190 Article])</ref> :[[Image:NBS Alpha-Bromination Scheme.png|350px|Alpha-bromination of hexanoyl chloride]] The reaction of [[enolate]]s, [[enol ether]]s, or [[enol acetate]]s with NBS is the preferred method of α-bromination as it is high-yielding with few side-products.<ref>Stotter, P. L.; Hill, K. A.; ''[[J. Org. Chem.]]'' '''1973''', ''38'', 2576.</ref><ref>Lichtenthaler, F. W.; ''et al.'' ''Synthesis'' '''1992''', 179.</ref> ===Bromination of aromatic derivatives=== Electron-rich [[aromatic]] compounds, such as [[phenol]]s, [[aniline]]s, and various aromatic [[heterocycle]]s<ref>Amat, M.; Hadida, S.; Sathyanarayana, S.; Bosch, J. ''[[Organic Syntheses]]'', Coll. Vol. 9, p.417 (1998); Vol. 74, p.248 (1997). ([http://www.orgsyn.org/orgsyn/prep.asp?prep=cv9p0417 Article])</ref>, can be brominated using NBS.<ref>Gilow, H. W.; Burton, D. E.; ''[[J. Org. Chem.]]'' '''1981''', ''46'', 2221.</ref><ref>Brown. W. D.; Gouliaev, A. H. ''[[Organic Syntheses]]'', Vol. 81, p.98 (2005). ([http://www.orgsyn.org/orgsyn/prep.asp?prep=v81p0098 Article])</ref> Using [[dimethylformamide|DMF]] as the solvent gives high levels of para-selectivity.<ref>Mitchell, R. H.; Lai, Y.-H.; Williams, R. V.; ''[[J. Org. Chem.]]'' '''1979''', ''44'', 4733.</ref> ===Hofmann rearrangement=== NBS, in the presence of a strong base, such as [[DBU (chemistry)|DBU]], reacts with primary [[amide]]s to produce a [[carbamate]] via the [[Hofmann rearrangement]].<ref>Keillor, J. W.; Huang, X. ''[[Organic Syntheses]]'', Coll. Vol. 10, p.549 (2004); Vol. 78, p.234 (2002). ([http://www.orgsyn.org/orgsyn/prep.asp?prep=v78p0234 Article])</ref> :[[Image:Hoffmann Rearrangement NBS.png|400px|The Hofmann rearrangement using NBS]] ===Selective oxidation of alcohols=== It is uncommon, but possible for NBS to oxidize alcohols. [[Elias James Corey|E. J. Corey]] ''et al.'' found that one can selectively [[redox|oxidize]] secondary [[alcohol]]s in the presence of primary alcohols using NBS in aqueous [[dimethoxyethane|DME]].<ref>[[Elias James Corey|Corey, E. J.]]; Ishiguro, M. ''[[Tetrahedron Lett.]]'' '''1979''', ''20'', 2745-2748.</ref> :[[Image:NBS Oxidation Corey.png|350px|The selective oxidation of alcohols using NBS]] ==Preparation== 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 [[precipitate]]s out and can be collected by filtration. 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 &deg;C water. ==Precautions== 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. ==References== {{Reflist}} ==See also== *[[Halohydrin formation reaction|Halohydrin formation]] ==External links== * Usage of [http://www.orgsyn.org/orgsyn/chemname.asp?nameID=36378 N-Bromosuccinimide in Organic Syntheses] {{DEFAULTSORT:Bromosuccinimide, N-}} [[Category:Organobromides]] [[Category:Reagents for organic chemistry]] [[Category:Imides]] [[de:N-Bromsuccinimid]] [[fr:N-Bromosuccinimide]] [[ja:N-ブロモスクシンイミド]] [[pl:NBS]] [[zh:N-溴代琥珀酰亚胺]]