Wohl–Ziegler bromination

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]

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

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

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]

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

⁠r_a/r_s⁠ = ⁠k_2a/k_2s⁠(1 + ⁠k_4a/k_3a⁠[Br₂])

Low bromine concentrations

⁠r_a/r_s⁠ = ⁠k_2a/k_2s⁠⁠k_3a/k_4a⁠[Br₂]

where ⁠r_a/r_s⁠ 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

• Free-radical halogenation