Halogenation reactions benzylic

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. 

Non-activated methyl groups are never attacked in these reactions toluene can be functionalized but isolation of the resulting benzyl halides from these PTC mixtures is difficult. Most remarkable is that strained hydrocarbons such as cubane (5) or 2,4-didehydroadamantane (6) can also be halogenated with conservation of the cage [27], in marked contrast with the halogenation reactions of these substrates with halogen radicals [40]. Dihalogenations with either the same or a differ-... 

The photocyclizations of halogenated A-benzyl-/ -phenethylamines576 are examples of reactions in which two aryl rings are connected by a chain of four atoms, one of which is a nitrogen atom. In the cases reported, one phenyl ring has a bromine atom and the other an iodine atom at the ortho position. As expected, products were formed via initial rupture of the carbon-iodine bond and these products still contained the bromine atom. In addition, however, some unexpected cyclization products were encountered, containing iodine instead of bromine. The formation of these products was ascribed to replacement of bromine by iodine in the intermediate cyclohexadienyl radicals. 

Chloroperoxidase Enantioselective oxidation of sulfides Enantioselective oxidation of racemic epoxyalcohols Oxidation of benzyl alcohol Epoxidation of styrene Asymmetric oxidations Halogenation reactions [11, 15,77] [15, 48] [14] [78] [79] [80]... 

The mechanism for halogenation at the benzylic position resembles other radical halogenation reactions, and so it involves initiation, propagation, and termination. Mechanism 18.10 illustrates the radical bromination of ethylbenzene using Bt2 (h or A). 

Scheme 11.4 illustrates some representative halogenation reactions. The reaction in Entry 1 was conducted by slow addition of bromine to excess 2-methylpentane at 60°C, with irradiation from a tungsten light bulb. The reaction in Entry 2 is a typical benzylic bromination, carried out at 125°C with irradiation from a sun lamp. Entries 3 and 4 are examples of NBS bromination using benzoyl peroxide as the initiator. Entry 3 is interesting in that none of the allylic isomer 2-bromo-3-heptene is found. Entries 5 and 6 are examples of chlorination by f-butyl hypochlorite in which the f-butoxy radical is the chain carrier. Note that in Entry 6, both the primary and secondary allylic products are formed. The reaction in Entry 7 uses sulfuryl chloride as the halogenation reagent. Note that in contrast to chlorination with CI2 (see p. 1021), the reaction shows selectivity for the benzylic position. 

We know that the more stable the radical, the faster it can be formed. This means that a hydrogen bonded to either a benzylic carbon or an allylic carbon will be preferentially substituted in a halogenation reaction. As we saw in Section 9.4, bromination is more highly regioselective than chlorination, so the percent of substitution at the benzylic or allylic carbon is greater for bromination. 

Researchers van der Broeke and coworkers[" created perfluoro-functionalized poly(propyleneimine) dendrimers (23 Fig. 4) and demonstrated their potential as phase-transfer catalysts in supercritical carbon-dioxide-water mixtures and as anionic species extractants. The dendrimers were accessed via reaction of perfluorinated, linear alkyl acid chlorides with the terminal amines. Extraction of perinanganate or dichromate from aqueous to CO2 solution was described as rather low, whereas their use as phase-transfer catalysts in a halogen exchange reaction [benzyl chloride to benzyi bromide (24)] resulted in high rates of conversion. 

PROBLEM 13.64 We answered questions about the StabiUzed alkene halogenation reaction in Chapter 10. This reaction is at the top of the Semester IB page. Watch it again to remind yourself about the pathway. Bromination in this animation is shown to occur via a syn addition. Bromination usually proceeds through an anti addition. Why would syn addition be favored over anti addition for this reaction Notice the benzyUc-Uke intermediate in the reaction. Do you suppose the napthylmethyl cation (Uke the one in this animation) is more stable than a benzyl cation Why ... 

The introduction of halogen substituents by free-radical substitution was discussed in Section 12.3 of Part A. Halogenation is a fairly general method for functionalization but is limited to the site in the molecule which is most reactive toward halogen atoms. Halogenations at benzylic and allylic positions are therefore the most useful synthetic reactions. 

Radical halogen reactions preferentially replace an H on an alkane according to the following order Benzylic > Allylic > Tertiary (3") > Secondary (2 ) > Primary (1 ) > Methyl (0 )... 

Sections Free radical halogenation and oxidation involve reactions at the benzylic 11 12-11 13 carbon See Table 112... 

The reactions of benzyl chloride, benzal chloride, and ben zotricbl oride may be divided into two classes (/) reactions of the side chain containing the halogen and (2) reactions of the aromatic ring. 

In many cases, substituents linked to a pyrrole, furan or thiophene ring show similar reactivity to those linked to a benzenoid nucleus. This generalization is not true for amino or hydroxyl groups. Hydroxy compounds exist largely, or entirely, in an alternative nonaromatic tautomeric form. Derivatives of this type show little resemblance in their reactions to anilines or phenols. Thienyl- and especially pyrryl- and furyl-methyl halides show enhanced reactivity compared with benzyl halides because the halogen is made more labile by electron release of the type shown below. Hydroxymethyl and aminomethyl groups on heteroaromatic nuclei are activated to nucleophilic attack by a similar effect. 

Important differences are seen when the reactions of the other halogens are compared to bromination. In the case of chlorination, although the same chain mechanism is operative as for bromination, there is a key difference in the greatly diminished selectivity of the chlorination. For example, the pri sec selectivity in 2,3-dimethylbutane for chlorination is 1 3.6 in typical solvents. Because of the greater reactivity of the chlorine atom, abstractions of primary, secondary, and tertiary hydrogens are all exothermic. As a result of this exothermicity, the stability of the product radical has less influence on the activation energy. In terms of Hammond s postulate (Section 4.4.2), the transition state would be expected to be more reactant-like. As an example of the low selectivity, ethylbenzene is chlorinated at both the methyl and the methylene positions, despite the much greater stability of the benzyl radical ... 

Many reactions of fluorinated organics with metal halides result in the replacement of fluorine with halogen A general route to 1,1,1-trichloro- or tribromo-fluoroalkanes involves treating primary fluoroalkyl iodides with aluminum trichloride or aluminum tribromide [74], Benzylic [75, 76] or vinylic [72] fluorine can be exchanged for chlorine when treated with aluminum trichloride... 

Nucleophilic substitution of the halogen atom of halogenomethylisoxazoles proceeds readily this reaction does not differ essentially from that of benzyl halides. One should note the successful hydrolysis of 4-chloromethyl- and 4-(chlorobenzyl)-isoxazoles by freshly precipitated lead oxide, a reagent seldom used in organic chemistry. Other halides, ethers, and esters of the isoxazole series have been obtained from 3- and 4-halogenomethylisoxazoles, and 3-chloro-methylisoxazole has been reported in the Arbuzov rearrangement. Panizzi has used dichloromethylisoxazole derivatives to synthesize isoxazole-3- and isoxazole-5-aldehydes/ ... 

The reaction of methane tricarboxylate with indoline 342 gave the tricyclic derivative 361 which can be transformed to the amide derivatives 362 (97JHC969). Alkylation of the iV-benzyl indoline 360 with pentafluor-oacetone gave 363 which upon debenzylation and subsequent acylation with diketene followed by cyclization gave 364. Other haloacetones were used to prepare different halogenated derivatives (79BEP872311) (Scheme 63). 

Chiral alcohols have also been used in an asymmetric synthesis of sulphoxides based on halogenation of sulphides. Johnson and coworkers have found319 that the reaction of benzyl p-tolyl sulphide with JV-chlorobenzotriazole (NCBT) followed by addition of (—) menthol and silver tetrafluoroborate afforded diastereoisomeric menthoxysulphonium salts 267 which, upon recrystallization and hydrolysis, gave benzyl p-tolyl sulphoxide with 87% optical purity (equation 145). More recently, Oae and coworkers reported320 that optically active diaryl sulphoxides (e.e. up to 20%) were formed either by hydrolysis or thermolysis of the corresponding diaryl menthoxysulphonium salts prepared in situ from diaryl sulphides using ( —) menthol and t-butyl hypochlorite. 

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