Wohl–Ziegler bromination
| Wohl–Ziegler bromination | |
|---|---|
| Named after | Alfred Wohl Karl Ziegler |
| Reaction type | Substitution reaction |
| Identifiers | |
| Organic Chemistry Portal | wohl-ziegler-reaction |
| RSC ontology ID | RXNO:0000225 |
The Wohl–Ziegler reaction[1][2] is a chemical reaction that involves the allylic or benzylic bromination of hydrocarbons using an N-bromosuccinimide and a radical initiator.[3]
Best yields are achieved with N-bromosuccinimide in carbon tetrachloride solvent. Several reviews have been published.[4][5]
In a typical setup, a stoichiometric amount of N-bromosuccinimide solution and a small quantity of initiator are added to a solution of the substrate in CCl4, and the reaction mixture is stirred and heated to the boiling point. Initiation of the reaction is indicated by more vigorous boiling; sometimes the heat source may need to be removed. Once all N-bromosuccinimide (which is denser than the solvent) has been converted to succinimide (which floats on top) the reaction has finished. Due to the high toxicity and ozone-depleting nature of carbon tetrachloride, trifluorotoluene has been proposed as an alternative solvent suitable for the Wohl–Ziegler bromination.[6]
The corresponding chlorination reaction cannot generally be achieved with N-chlorosuccinimide,[7] although more specialized reagents have been developed,[8] and the reaction can be achieved industrially with chlorine gas.[9]
Mechanism
[edit]The Wohl–Ziegler reaction proceeds through a mechanism first proposed by Paul Goldfinger in 1953.[10][11] An earlier mechanism proposed by George Bloomfield, though consistent with selectivity studies, proved overly simplistic.[10]
![Goldfinger and Bloomfield mechanisms[10]](/wiki/File:Goldfinger_and_Bloomfield_Mechanisms.png)
The key puzzle in mechanizing the Wohl–Ziegler reaction is the role of the succinimide moiety. Bloomfield's mechanism required direct NBS radicals.[12] But the N–Br bond has dissociation energy much larger than that for Br2,[11][13] and rarely homolyzes like Bloomfield expected.[10][11]
Goldfinger instead explains the necessity of succinimide through competing addition and substitution pathways.[13] These pathways apply to almost all radical reactions, and a generic depiction (including side-reactions 6 and 8) is as follows:[14]
Relative rate laws describing each pathway depend strongly on the molecular bromine concentration. The limiting cases of high and low concentration are:
- High bromine concentrations
- ra/rs = k2a/k2s(1 + k4a/k3a[Br2])
- Low bromine concentrations
- ra/rs = k2a/k2sk3a/k4a[Br2]
where ra/rs is the ratio of addition to substitution, and the k values correspond to the rate constant for the labeled reaction step.[13]
The desired bromination is the substitution product. As the above equations indicate, addition is suppressed as [Br2] decreases.[13] Goldfinger thus concludes that as NBS acts primarily as a bromine sink, promoting substitution through a very low Br2 concentration.[13][10]
See also
[edit]References
[edit]- ^ Alfred Wohl (1919). "Bromierung ungesättigter Verbindungen mit N-Brom-acetamid, ein Beitrag zur Lehre vom Verlauf chemischer Vorgänge". Berichte der deutschen chemischen Gesellschaft. 52: 51–63. doi:10.1002/cber.19190520109.
- ^ Ziegler, K., G. Schenck, E. W. Krockow, A. Siebert, A. Wenz, H. Weber (1942). "Die Synthese des Cantharidins". Justus Liebig's Annalen der Chemie. 551: 1–79. doi:10.1002/jlac.19425510102.
{{cite journal}}: CS1 maint: multiple names: authors list (link) - ^ Greenwood, F. L.; Kellert, M. D.; Sedlak, J. (1963). "4-Bromo-2-heptene". Organic Syntheses; Collected Volumes, vol. 4, p. 108.
- ^ C. 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.
- ^ Horner, L; Winkelman, E. M (1959). "Neuere Methoden der präparativen organischen Chemie II 14. N-Bromsuccinimid, Eigenschaften und Reaktionsweisen Studien zum Ablauf der Substitution XV". Angew. Chem. 71 (11): 349. Bibcode:1959AngCh..71..349H. doi:10.1002/ange.19590711102.
- ^ Suarez, Diana; Laval, Gilles; Tu, Shang-Min; Jiang, Dong; Robinson, Claire L.; Scott, Richard; Golding, Bernard T. (June 2009). "Benzylic Brominations with N-Bromosuccinimide in (Trifluoromethyl)benzene". Synthesis. 2009 (11): 1807–1810. doi:10.1055/s-0029-1216793. ISSN 1437-210X.
- ^ Djerassi, Carl. (1948-10-01). "Brominations with N-Bromosuccinimide and Related Compounds. The Wohl-Ziegler Reaction". Chemical Reviews. 43 (2): 271–317. doi:10.1021/cr60135a004. ISSN 0009-2665. PMID 18887958.
- ^ Theilacker, Walter; Wessel, Heinz (1967). "Olefinreaktionen, I. Chlorierung in Allyl-Stellung". Justus Liebigs Annalen der Chemie (in German). 703 (1): 34–36. doi:10.1002/jlac.19677030105. ISSN 1099-0690.
- ^ Krähling, Ludger; Krey, Jürgen; Jakobson, Gerald; Grolig, Johann; Miksche, Leopold (2000), "Allyl Compounds", Ullmann's Encyclopedia of Industrial Chemistry, American Cancer Society, doi:10.1002/14356007.a01_425, ISBN 9783527306732
- ^ a b c d e Incremona, J.H.; Martin, J.C. (1970). "N-Bromosuccinimide. Mechanisms of Allylic Bromination and Related Reactions". J. Am. Chem. Soc. 92 (3): 627–634. Bibcode:1970JAChS..92..627I. doi:10.1021/ja00706a034.
- ^ a b c Nonhebel, D.C.; Walton, J.C. (1974). Free Radical Chemistry: Structure and Mechanism. London: Cambridge University Press. pp. 191–193. ISBN 978-0521201490.
- ^ Bloomfield, G.F. (1944). "Rubber, Polyisoprenes, and Allied Compounds. Part VI. The Mechanism of Halogen-substitution Reactions, and the Additive Halogenation of Rubber and Dihydromyrcene". J. Am. Chem. Soc.: 114–120. doi:10.1039/JR9440000114.
- ^ a b c d e Adam, J.; Gosselain, P.A.; Goldfinger, P. (1953). "Laws of Addition and Substitution in Atomic Reactions of Halogens". Nature. 171 (4355): 704–705. Bibcode:1953Natur.171..704A. doi:10.1038/171704b0. S2CID 4285312.
- ^ Neuman, R.C. (1992). Organic Chemistry. Online: Robert C. Neuman, Jr.