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N-Bromosuccinimide

December 02, 2023

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

N-Bromosuccinimide
Names
Preferred IUPAC name
1-Bromopyrrolidine-2,5-dione
Other names
N-bromosuccinimide; NBS
Identifiers
  • 128-08-5 Y
3D model (JSmol)
  • Interactive image
113916
ChEBI
  • CHEBI:53174 Y
ChemSpider
  • 60528 Y
ECHA InfoCard 100.004.435
EC Number
  • 204-877-2
26634
  • 67184
UNII
  • K8G1F2UCJF
  • DTXSID2038738
  • 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
  • O=C1N(Br)C(=O)CC1
Properties
C4H4BrNO2
Molar mass 177.985 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)
14.7 g/L (25 °C)
Solubility in CCl4 Insoluble (25 °C)
Hazards
Occupational safety and health (OHS/OSH):
Main hazards
 Irritant
Safety data sheet (SDS) [1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
Y verify (what is YN ?)

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 and can be collected by filtration.[1]

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 to 95 °C water (10 g of NBS for 100 mL of water).[2]

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.[3] Formation of a bromonium ion and immediate attack by water gives strong Markovnikov addition and anti stereochemical selectivities.[4]

 

Side reactions include the formation of α-bromoketones 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.[5]

 

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 azobisisobutyronitrile (AIBN) or benzoyl peroxide, irradiation, or both to effect radical initiation.[6][7] 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.[8][9]

 

The carbon tetrachloride must be maintained anhydrous throughout the reaction, as the presence of water may likely hydrolyze the desired product.[10] 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.[11]

 

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.[12][13]

Bromination of aromatic derivatives edit

Electron-rich aromatic compounds, such as phenols, anilines, and various aromatic heterocycles,[14] can be brominated using NBS.[15][16] Using DMF as the solvent gives high levels of para-selectivity.[17]

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.[18]

 

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).[19]

 

Oxidative decarboxylation of α-amino acids edit

NBS electrophilically brominates the amine, which is followed by decarboxylation and release of an imine. Further hydrolysis will yield an aldehyde and ammonia.[20][21] (cf. non-oxidative PLP dependent decarboxylation)

 

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 using on a large scale.

See also edit

References edit

  1. ^ Ziegler, K.; Späth, A. (1942). "Die Halogenierung ungesättigter Substanzen in der Allylstellungs". Ann. Chem. 551 (1): 80–119. doi:10.1002/jlac.19425510103.
  2. ^ Dauben, H. J. Jr; 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.
  3. ^ Hanzlik, R. P. "Selective epoxidation of terminal double bonds". Organic Syntheses.; Collective Volume, vol. 6, p. 560
  4. ^ Beger, J. (1991). "Präparative Aspekte elektrophiler Dreikomponentenreaktionen mit Alkenen" [Preparative aspects of electrophilic three-component reactions with alkenes]. J. Prakt. Chem. 333 (5): 677–698. doi:10.1002/prac.19913330502.
  5. ^ Haufe, G.; Alvernhe, G.; Laurent, A.; Ernet, T.; Goj, O.; Kröger, S.; Sattler, A. (2004). "Bromofluorination of alkenes". Organic Syntheses.; Collective Volume, vol. 10, p. 128
  6. ^ Djerassi, Carl (1948). "Brominations with N-Bromosuccinimide and Related Compounds. The Wohl–Ziegler Reaction". Chem. Rev. 43 (2): 271–317. doi:10.1021/cr60135a004. PMID 18887958.
  7. ^ Greenwood, F. L.; Kellert, M. D.; Sedlak, J. (1958). "4-Bromo-2-heptene". Organic Syntheses. 38: 8. doi:10.15227/orgsyn.038.0008.
  8. ^ Wohl, A. (1919). "Bromierung ungesättigter Verbindungen mit N-Brom-acetamid, ein Beitrag zur Lehre vom Verlauf chemischer Vorgänge" [Bromination of unsaturated compounds with N-bromoacetamide, a contribution to the theory of the course of chemical processes]. Berichte der Deutschen Chemischen Gesellschaft (A and B Series). 52: 51–63. doi:10.1002/cber.19190520109.
  9. ^ Ziegler, K.; Schenck, G.; Krockow, E. W.; Siebert, A.; Wenz, A.; Weber, H. (1942). "Die Synthese des Cantharidins" [The synthesis of cantharidin]. Justus Liebig's Annalen der Chemie. 551: 1–79. doi:10.1002/jlac.19425510102.
  10. ^ 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.
  11. ^ Harpp, D. N.; Bao, L. Q.; Coyle, C.; Gleason, J. G.; Horovitch, S. (1988). "2-Bromohexanoyl chloride". Organic Syntheses.; Collective Volume, vol. 6, p. 190
  12. ^ 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.
  13. ^ Lichtenthaler, F. W. (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: 179–84. doi:10.1055/s-1992-34167.
  14. ^ Amat, M.; Hadida, S.; Sathyanarayana, S.; Bosc, J. (1998). "Regioselective synthesis of 3-substituted indoles". Organic Syntheses.; Collective Volume, vol. 9, p. 417
  15. ^ 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.
  16. ^ Brown, W. D.; Gouliaev, A. H. (2005). "Synthesis of 5-bromoisoquinoline and 5-bromo-8-nitroisoquinoline". Organic Syntheses. 81: 98.
  17. ^ 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.
  18. ^ Keillor, J. W.; Huang, X. (2004). "Methyl carbamate formation via modified Hofmann rearrangement reactions". Organic Syntheses.; Collective Volume, vol. 10, p. 549
  19. ^ 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.
  20. ^ Ramachandran, M. S.; Easwaramoorthy, D.; Rajasingh, V.; Vivekanandam, T. S. (1990-01-01). "N-Chlorosuccinimide-Promoted Oxidative Decarboxylation of α-Amino Acids in Aqueous Alkaline Medium". Bulletin of the Chemical Society of Japan. 63 (8): 2397–2403. doi:10.1246/bcsj.63.2397.
  21. ^ Song, Xuezheng; Ju, Hong; Zhao, Chunmei; Lasanajak, Yi (2014-10-15). "Novel Strategy to Release and Tag N-Glycans for Functional Glycomics". Bioconjugate Chemistry. 25 (10): 1881–1887. doi:10.1021/bc500366v. ISSN 1043-1802. PMC 4197647. PMID 25222505.

External links edit

  • Usage of
  • Reactions with NBS

December 02, 2023
bromosuccinimide, chemical, reagent, used, radical, substitution, electrophilic, addition, electrophilic, substitution, reactions, organic, chemistry, convenient, source, bromine, radical, namespreferred, iupac, name, bromopyrrolidine, dioneother, names, bromo. N Bromosuccinimide or NBS is a chemical reagent used in radical substitution electrophilic addition and electrophilic substitution reactions in organic chemistry NBS can be a convenient source of Br the bromine radical N Bromosuccinimide NamesPreferred IUPAC name 1 Bromopyrrolidine 2 5 dioneOther names N bromosuccinimide NBSIdentifiersCAS Number 128 08 5 Y3D model JSmol Interactive imageBeilstein Reference 113916ChEBI CHEBI 53174 YChemSpider 60528 YECHA InfoCard 100 004 435EC Number 204 877 2Gmelin Reference 26634PubChem CID 67184UNII K8G1F2UCJFCompTox Dashboard EPA DTXSID2038738InChI InChI 1S C4H4BrNO2 c5 6 3 7 1 2 4 6 8 h1 2H2 YKey PCLIMKBDDGJMGD UHFFFAOYSA N YInChI 1 C4H4BrNO2 c5 6 3 7 1 2 4 6 8 h1 2H2Key PCLIMKBDDGJMGD UHFFFAOYASSMILES O C1N Br C O CC1PropertiesChemical formula C 4H 4Br N O 2Molar mass 177 985 g mol 1Appearance White solidDensity 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 14 7 g L 25 C Solubility in CCl4 Insoluble 25 C HazardsOccupational safety and health OHS OSH Main hazards IrritantSafety data sheet SDS 1 Except where otherwise noted data are given for materials in their standard state at 25 C 77 F 100 kPa Y verify what is Y N Infobox references 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 a amino acids 3 Precautions 4 See also 5 References 6 External linksPreparation editNBS 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 and can be collected by filtration 1 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 to 95 C water 10 g of NBS for 100 mL of water 2 Reactions editAddition 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 3 Formation of a bromonium ion and immediate attack by water gives strong Markovnikov addition and anti stereochemical selectivities 4 nbsp Side reactions include the formation of a bromoketones 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 5 nbsp 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 azobisisobutyronitrile AIBN or benzoyl peroxide irradiation or both to effect radical initiation 6 7 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 8 9 nbsp The carbon tetrachloride must be maintained anhydrous throughout the reaction as the presence of water may likely hydrolyze the desired product 10 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 a 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 11 nbsp The reaction of enolates enol ethers or enol acetates with NBS is the preferred method of a bromination as it is high yielding with few side products 12 13 Bromination of aromatic derivatives edit Electron rich aromatic compounds such as phenols anilines and various aromatic heterocycles 14 can be brominated using NBS 15 16 Using DMF as the solvent gives high levels of para selectivity 17 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 18 nbsp 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 19 nbsp Oxidative decarboxylation of a amino acids edit NBS electrophilically brominates the amine which is followed by decarboxylation and release of an imine Further hydrolysis will yield an aldehyde and ammonia 20 21 cf non oxidative PLP dependent decarboxylation nbsp Precautions editAlthough 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 using on a large scale See also editHalohydrin formation N Chlorosuccinimide N IodosuccinimideReferences edit Ziegler K Spath A 1942 Die Halogenierung ungesattigter Substanzen in der Allylstellungs Ann Chem 551 1 80 119 doi 10 1002 jlac 19425510103 Dauben H J Jr 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 Organic Syntheses Collective Volume vol 6 p 560 Beger J 1991 Praparative Aspekte elektrophiler Dreikomponentenreaktionen mit Alkenen Preparative aspects of electrophilic three component reactions with alkenes J Prakt Chem 333 5 677 698 doi 10 1002 prac 19913330502 Haufe G Alvernhe G Laurent A Ernet T Goj O Kroger S Sattler A 2004 Bromofluorination of alkenes Organic Syntheses Collective Volume vol 10 p 128 Djerassi Carl 1948 Brominations with N Bromosuccinimide and Related Compounds The Wohl Ziegler Reaction Chem Rev 43 2 271 317 doi 10 1021 cr60135a004 PMID 18887958 Greenwood F L Kellert M D Sedlak J 1958 4 Bromo 2 heptene Organic Syntheses 38 8 doi 10 15227 orgsyn 038 0008 Wohl A 1919 Bromierung ungesattigter Verbindungen mit N Brom acetamid ein Beitrag zur Lehre vom Verlauf chemischer Vorgange Bromination of unsaturated compounds with N bromoacetamide a contribution to the theory of the course of chemical processes Berichte der Deutschen Chemischen Gesellschaft A and B Series 52 51 63 doi 10 1002 cber 19190520109 Ziegler K Schenck G Krockow E W Siebert A Wenz A Weber H 1942 Die Synthese des Cantharidins The synthesis of cantharidin Justus Liebig s Annalen der Chemie 551 1 79 doi 10 1002 jlac 19425510102 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 Organic Syntheses Collective Volume vol 6 p 190 Stotter P L Hill K A 1973 a Halocarbonyl compounds II Position specific preparation of a bromoketones by bromination of lithium enolates Position specific introduction of a b unsaturation into unsymmetrical ketones J Org Chem 38 14 2576 doi 10 1021 jo00954a045 Lichtenthaler F W 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 179 84 doi 10 1055 s 1992 34167 Amat M Hadida S Sathyanarayana S Bosc J 1998 Regioselective synthesis of 3 substituted indoles Organic Syntheses Collective Volume vol 9 p 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 Organic Syntheses 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 Organic Syntheses Collective Volume vol 10 p 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 Ramachandran M S Easwaramoorthy D Rajasingh V Vivekanandam T S 1990 01 01 N Chlorosuccinimide Promoted Oxidative Decarboxylation of a Amino Acids in Aqueous Alkaline Medium Bulletin of the Chemical Society of Japan 63 8 2397 2403 doi 10 1246 bcsj 63 2397 Song Xuezheng Ju Hong Zhao Chunmei Lasanajak Yi 2014 10 15 Novel Strategy to Release and Tag N Glycans for Functional Glycomics Bioconjugate Chemistry 25 10 1881 1887 doi 10 1021 bc500366v ISSN 1043 1802 PMC 4197647 PMID 25222505 External links editUsage of N bromosuccinimide in organic synthesis Reactions with NBS Retrieved from https en wikipedia org w index php title N Bromosuccinimide amp oldid 1183018443, wikipedia, wiki, book, books, library,

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