Halogenation, radical, allylic reaction

This allylic bromination with NBS is analogous to the alkane halogenation reaction discussed in the previous section and occurs by a radical chain reaction pathway. As in alkane halogenation, Br- radical abstracts an allylic hydrogen atom of the alkene, thereby forming an allylic radical plus HBr. This allylic radical then reacts with Br2 to yield the product and a Br- radical, which cycles back... 

Wohl in 1919 reported that A -bromoacetamide (CH CONHBr) induced allylic bromination. " Then iV-bromosuccinimide (30) was described in 1942 by Ziegler and co-workers to be useful in such free radical bromination reactions (equation 41), " and this widely utilized procedure is known as the Wohl-Ziegler reaction. In 1963 the mechanism of the reaction was proposed to involve halogen atoms in the hydrogen abstraction step " " " instead of succinimidyl radicals as had been commonly supposed. The halogen atom mechanism had previously been proposed by Gosselain et al. for reactions of yV-chlorosuccinimide. " ... 

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. 

Radical substitution reactions involving allylic tin derivatives could be accompanied by a photoinduced 1,3-rearrangement54,55. A photostationary mixture of cinnamyl(tri-phenyl)stannane with its regioisomer l-phenylprop-2-enyl(triphenyl)stannane has been shown to form in the photolysis of ( )-cinnamyl(triphenyl)stannane in benzene under aerobic conditions, or in the presence of halogenated organic compounds or radicaltrapping reagents (equation 21). 

Addition Reactions.- The photoelectron transfer process of the iminium salt (38) with the 3-butenoate anion results in the formation of the allylated product (39). The reaction involves decarboxylation of the 3-butenoate followed by a radical coupling reaction. The photoaddition of halogenated alkenes to the tetraraza phenanthrene (40) yields products (41) of (2+2)-addition. The Eu(III)/Eu(II) photoredox system has been studied with regards to its reactivity toweu ds a-methylstyrene. Irradiation of the system at > 280 nm in methanol yielded the products (42) and(43). ... 

The EtsB-induced halogen atom transfer radical cyclization reaction is a successful application. Cyclization of iodo acetal 44 afforded the tetrahydrofuran derivative 45 in almost quantitative yield (Scheme 26) [32]. Et3B also induced radical cyclization of A -allylic a-iodoacetamide to give y9-iodomethyl-y-lactam via an atom transfer process [34]. The reaction of 46 prepared from 2-prolinol proceeded smoothly within 10 min in boiling benzene in the presence of Et3B to yield IR, 8S)-... 

Allylic bromination by NBS is a radical-chain reaction occurring on the surface of the NBS crystals. A solution of NBS in tetrachloroethane or nitro-methane adds bromide to a C=C group 354 solvents are therefore used in which NBS and, if possible, also the succinimide formed, are difficultly soluble dry CC14 is usually chosen, but for reactive substances cyclohexane or benzene may also be used. The more polarized the N-halogen is, i.e.9 the more positive the Br is rendered, the more easily does the A-halogenated compound cause addition to the C=C bond NBS is particularly suitable for allylic bromination because of its steric structure and the almost apolar nature of its N-Br bond. 

Allylic hydrogens are especially reactive in radical substitution reactions. We can synthesize allylic halides by substitution of allylic hydrogens. For example, when propene reacts with bromine or chlorine at high temperatures or under radical conditions where the concentration of the halogen is small, the result is allylic substitution. 

There are some instances where the chlorination or bromination reaction can be used to good effect, however. Alkenes that have allylic hydrogens can sometimes be halogenated specifically at an allylic position in a process called allylic halogenation, another free radical chain reaction. For example, when low concentrations of bromine are photolyzed in the presence of the complicated cyclohexene shown in Figure 11.51, the product is exclusively brominated in one allylic position. 

The nucleophilic displacement of active halogens in allylic halides to give allylic tellurides is effected by an even simpler reagent than either (300) or (301), i.e. Te -. Once formed, the allylic tellurides decompose spontaneously to allyl radicals which couple to form 1,5-dienes, a reaction in which tellurium appears to be far superior to selenium. 

In earlier years, radical allyl halogenations and selenium dioxide oxidation were quite popular, although in various ways problematic. Nowadays, catalytic hydroxy-lations or ene-reactions with singlet oxygen are the better accepted alternatives. 

A consequence of delocalization is that resonance-stabilized allylic intermediates can readily participate in reactions of unsaturated molecules. For example, although halogens can add to aUcenes to give the corresponding vicinal dihalides (Section 12-5) by an ionic mechaiusm, the course of this reaction is changed with added radical iiutiators (or on irradiation) and with the halogen present only in low concentrations. These conditions slow the ionic addition pathway sufficiently to allow a faster radical chain mechanism to take over, leading to radical allylic substitution. ... 

The catalysis by Yb(OTf)3-Me3SiCl is quite useful for allylic halogenation of 1,1-disubstituted alkenes with NBS, NCS and NIS [157]. In contrast to the conventional method using a radical initiator, this method does not cause benzylic halogenation. Thus, the reaction of l-isopropenyl-2-methylbenzene with NBS and NCS gives allyl halides in good yield without benzylic halogenation (Scheme 9.66). 

Bromination with A-bromosuccinimide generally gives the same result as bromination with free bromine or hypobromous acid. The reaction is considered to proceed with a small concentration of free bromine and does not generate an appreciable concentration of acid. Conditions are therefore mild. In addition, A-bromosuccinimide has been used to brominate the allylic position of a, -unsaturated ketones in the presence of free-radical promoters or with irradiation, and thus gives access to dienones by dehydro-halogenation, for exaraple " ... 

A -Halogenated compounds such as iV-chlorotnfluoroacetamide, A -chloro-imidosulfuryl fluonde and N N dichlorotnfluoromethylamine add across C=C bonds to form saturated amides [14] tmidosulfury I fluorides [15] and amines [16], respectively Allylic halogenation also occurs with the use of A-bromo- or A-chIo roperfluoroamides The primary amine A,A-dichlorotrifluororaethylamine selectively affords 11 or 2 1 adducts with either tetrafluoroethylene or chlorotrifluoroethylene [16] (equation 7) The reaction mechanism is believed to involve thermal free radicals, with control achieved principally by reaction temperature The 1 1 adduct is formed even in the presence of a large excess of olefin... 

Simple alkyl halides can be prepared by radical halogenation of alkanes, but mixtures of products usually result. The reactivity order of alkanes toward halogenation is identical to the stability order of radicals R3C- > R2CH- > RCH2-. Alkyl halides can also be prepared from alkenes by reaction with /V-bromo-succinimide (NBS) to give the product of allylic bromination. The NBS bromi-nation of alkenes takes place through an intermediate allylic radical, which is stabilized by resonance. 

---