Allylic and Benzylic Halogenation

In addition to cation intermediates, radical intermediates can be used to introduce bromine or chlorine into a molecule. Both allylic and benzylic moieties form resonance stabilized free radicals that react with bromine or chlorine to give the corresponding halide. Allylic radicals are easily accessible from the corresponding allylic halides, particularly allyl iodides (secs. 13.3-13.5). Benzylic radicals are available from benzylic halides and also directly from the hydrocarbon, if it bears a benzylic hydrogen. Addition of bromine to 167 (in the presence benzoyl peroxide and photochemical initiation) gave benzylic bromide 168 in high 

A more convenient method for halogenation of allylic and benzylic C-H moieties uses the readily available A-bromosuccinimide (NBS, 170) or NCS (173) with heat and/or light, in what is called the Wohl-Ziegler reaction. Reaction of NBS with cyclohexene in refluxing carbon tetrachloride gives bromocyclo- 

Ketones containing an enolizable hydrogen can be halogenated at the a position (the carbon adjacent to the carbonyl) with bromine, chlorine, NBS, or NCS. The reaction probably proceeds via addition of X2 to the enol form of the carbonyl (secs. 9.2.A, 9.8.A). Elimination of HX from the addition product generates an other enol, which tautomerizes to the a-haloketone. Reaction of cyclohexanone with bromine, for example, would give 2-bromocyclohexanone (174) and a similar reaction with NCS (173) would give 2-chloro-cyclohexanone (172). 

Halogenation usually occurs preferentially at the more highly substituted a position of unsymmetrical ketones. Regioselectivity can be a problem in the halogenation of unsymmetrical ketones, but heating a ketone with ferf-butyl bromide and DMSO at 65°C is a mild and selective solution to the problem, and it 

Chapter 2. Acids, Bases, Functional Group Exchanges 

---

NBS also works well for brominating benzylic positions, next to an aromatic ring (see Problem 6-10). Allylic and benzylic halogenations are discussed in more detail in Chapter 15. 

Allylic and Benzylic Halogenation Halogenation or Halo-de-hydrogenation... 

Radical Allylic and Benzylic Halogenation (WoHL-ZlEGLER BrOMINATION)... 

Differences in solubility of the reactants may for example be utilized as follows. Sodium iodide is much more soluble in acetone than are sodium chloride or sodium bromide. Upon treatment of an alkyl chloride or bromide with sodium iodide in acetone, the newly formed sodium chloride or bromide precipitates from the solution and is thus removed from equilibrium. Alkyl iodides can be conveniently prepared in good yields by this route. Alkyl bromides are more reactive as the corresponding chlorides. Of high reactivity are a-halogen ketones, a-halogen carboxylic acids and their derivatives, as well as allyl and benzyl halides. 

The relative stabilities of radicals follow the same trend as for carhoca-tions. Like carbocations, radicals are electron deficient, and are stabilized by hyperconjugation. Therefore, the most substituted radical is most stable. For example, a 3° alkyl radical is more stable than a 2° alkyl radical, which in turn is more stable than a 1° alkyl radical. Allyl and benzyl radicals are more stable than alkyl radicals, because their unpaired electrons are delocalized. Electron delocalization increases the stability of a molecule. The more stable a radical, the faster it can be formed. Therefore, a hydrogen atom, bonded to either an allylic carbon or a benzylic carbon, is substituted more selectively in the halogenation reaction. The percentage substitution at allylic and benzyhc carbons is greater in the case of bromination than in the case of chlorination, because a bromine radical is more selective. 

Show how free-radical halogenation might be used for the synthesis of some alkyl halides, especially for making allylic and benzylic alkyl halides. 

These reactions are based on hydrogen fluoride and involve, essentially, a nucleophilic displacement of halogen (for convenience, in the sense intended throughout this book, this term usually excludes fluorine). However, only the most reactive halides such as allylic and benzylic ones can be fluorinated by anhydrous HF alone [9] (Figure 2.2). 

Allylic halides and benzylic halides have halogen atoms bonded to sp hybridized carbon atoms and do undergo the reactions described in Chapter 7. Allylic halides have X bonded to the carbon atom adjacent to a carbon-carbon double bond, and benzylic halides have X bonded to the carbon atom adjacent to a benzene ring. The synthesis of allylic and benzylic halides is discussed in Sections 15.10 and 18.13, respectively. 

Resonance effects. Conjugation with a double bond increases the stability of a carbocation. Thus, allylic and benzylic cations are more stable than their saturated counterparts. (For example, see Problem 1.4.c.) Heteroatoms with unshared electron pairs, e.g., oxygen, nitrogen, or halogen, can also provide resonance stabilization for cationic centers, as in the following examples ... 

We have seen (Sec. 14.24) that an alkyl halide is conveniently detected by the precipitation of insoluble silver halide when it is warmed with alcoholic silver nitrate. The reaction occurs nearly instantaneously with tertiary, allyl, and benzyl bromides, and within five minutes or so with primary and secondary bromides. Compounds containing halogen joined directly to an aromatic ring or to a doubly-bonded carbon, however, do not yield silver halide under these conditions. Bromo-benzene or vinyl bromide can be heated with alcoholic AgN03 for days without the slightest trace of AgBr being detected. In a similar way, attempts to convert aryl... 

Allylic and benzylic heteroatom substituents such as -OR, -SR, and halogens undergo concomitant hydrogenolysis during Birch reduction. However, benzylic -OH groups are converted to alkoxides, and the resultant electron-rich -CHjO moiety resists further reduction. 

In addition to Br2, H-bromosuccinimide is an important reagent for radical chain bromination, especially at allylic and benzylic positions. Mechanistic investigations have established that Br2 is the active halogenating agent under the conditions used... 

---