| N-Bromosuccinimide |
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IUPAC name
1-Bromo-2,5-pyrrolidinedione
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| Identifiers |
| CAS number |
128-08-5 Y |
| ChemSpider |
60528 Y |
| ChEBI |
CHEBI:53174 Y |
| Jmol-3D images |
Image 1 |
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InChI=1S/C4H4BrNO2/c5-6-3(7)1-2-4(6)8/h1-2H2 Y
Key: PCLIMKBDDGJMGD-UHFFFAOYSA-N Y
InChI=1/C4H4BrNO2/c5-6-3(7)1-2-4(6)8/h1-2H2
Key: PCLIMKBDDGJMGD-UHFFFAOYAS
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| Properties |
| Molecular formula |
C4H4BrNO2 |
| Molar mass |
177.98 g mol−1 |
| Appearance |
White solid |
| Density |
2.098 g/cm3 (solid) |
| Melting point |
175 to 178 °C (347 to 352 °F; 448 to 451 K) |
| Boiling point |
339 °C (642 °F; 612 K) |
| Solubility in water |
1.47 g / 100 mL (25 °C) |
| Solubility in CCl4 |
Insoluble (25 °C) |
| Hazards |
| MSDS |
[1] |
| Main hazards |
Irritant |
| Except where noted otherwise, data are given for materials in their standard state (at 25 °C (77 °F), 100 kPa) |
| Y (verify) (what is: Y/N?) |
| Infobox references |
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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 Br•, the bromine radical.
Contents
- 1 Preparation
- 2 Reactions
- 2.1 Addition to alkenes
- 2.2 Allylic and benzylic bromination
- 2.3 Bromination of carbonyl derivatives
- 2.4 Bromination of aromatic derivatives
- 2.5 Hofmann rearrangement
- 2.6 Selective oxidation of alcohols
- 2.7 Oxidative decarboxylation of amino acids
- 3 Precautions
- 4 See also
- 5 References
- 6 External links
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 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 in color) may give unreliable results. It can be purified by recrystallization from 90–95°C water (10 g of NBS for 100 mL of water).[1]
Reactions
Addition to alkenes
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]
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]
Allylic and benzylic bromination
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]
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
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]
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
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
NBS, in the presence of a strong base, such as DBU, reacts with primary amides to produce a carbamate via the Hofmann rearrangement.[17]
Selective oxidation of alcohols
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]
Oxidative decarboxylation of amino acids
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
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
References
- ^ 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.
- ^ Hanzlik, R. P., "Selective epoxidation of terminal double bonds", Org. Synth. ; Coll. Vol. 6: 560
- ^ Beger, J. (1991). "Präparative Aspekte elektrophiler Dreikomponentenreaktionen mit Alkenen". J. Prakt. Chem. 333 (5): 677–698. doi:10.1002/prac.19913330502.
- ^ Haufe, G.; Alvernhe, G.; Laurent, A.; Ernet, T.; Goj, O.; Kröger, S.; Sattler, A. (2004), "Bromofluorination of alkenes", Org. Synth. ; Coll. Vol. 10: 128
- ^ 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.
- ^ F. L. Greenwood; M. D. Kellert; J. Sedlak (1963), "4-Bromo-2-heptene", Org. Synth. ; Coll. Vol. 4: 108
- ^ A. Wohl (1919). Ber. 52: 51.
- ^ Karl Ziegler, et al. (1942). Annalen der Chemie 551: 30.
- ^ 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.
- ^ Harpp, D. N.; Bao, L. Q.; Coyle, C.; Gleason, J. G.; Horovitch, S. (1988), "2-Bromohexanoyl chloride", Org. Synth. ; Coll. Vol. 6: 190
- ^ 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.
- ^ Lichtenthaler, F. W.; Stewart, JM; O'dea, DJ; Shapiro, GC; Patel, MB; Mcintyre, JT; Gewitz, MH; Hoegler, CT; Shapiro, JT; Zeballos, GA (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.
- ^ Amat, M.; Hadida, S.; Sathyanarayana, S.; Bosch, J. (1998), "Regioselective synthesis of 3-substituted indoles", Org. Synth. ; Coll. Vol. 9: 417
- ^ 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.
- ^ Brown. W. D.; Gouliaev, A. H. (2005), "Synthesis of 5-bromoisoquinoline and 5-bromo-8-nitroisoquinoline", Org. Synth. 81: 98
- ^ 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.
- ^ Keillor, J. W.; Huang, X. (2004), "Methyl carbamate formation via modified Hofmann rearrangement reactions", Org. Synth. ; Coll. Vol. 10: 549
- ^ 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
- Usage of N-Bromosuccinimide in Organic Syntheses
- Reactions with NBS
