Benzyhc carbon

The aromaticity of the nng is retained when chlorine bonds to the benzyhc carbon aro maticity is lost when chlorine bonds to one of the ring carbons... 

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. 

SoHman et al. reported the synthesis of 3-triphenylphosphoranylidene-chromanes 117 from Mannich bases 115 of the commercial moUusddde niclosamide and the ciunulated yhdes 2, 82 or 88 [73]. The reaction was carried out in boihng toluene and is thought to proceed by initial addition to give the acyl ylides 116, which then cycHze by the unusual expulsion of a secondary amine, i.e. by nudeophihc attack of the ylidic carbon atom at the benzyhc carbon atom. Intermediates 116 were not isolated. The moUusdddal activities of compounds 117 were found to be about tenfold lower than that of the parent niclosamide (Scheme 25). 

In order to achieve bromination at benzyhc carbons a different set of conditions were used. Specifically, TMS-Br was mixed with sodium bromate in carbon tetrachloride (CCI4) between room temperature and reflux. An example of this reaction, which is be-heved to proceed via a radical chain reaction mechanism, is the selective bromination of phenylacetonitrile (eq 37). ... 

Despite this, anaerobes offer rewards to those who persevere by providing for the discovery of the most novel biochemical reactions on Earth. Some of these reactions have recently been elucidated. For example, bacteria are now known to cataboHze toluene anaerobically. They initiate attack on the benzyHc carbon via a radical mechanism that generates a new carbon-carbon bond to form benzylsuccinate as the first metabolite (Leuthner et al. 1998). Others, such as the anaerobic formation of methane from long-chain alkanes (Zengler et al. 1999), remain obscme biochemically. 

A carbonyl group bonded to a benzene ring can also be directly reduced by catalytic hydrogenation. This reaction only occurs at the benzyhc carbon if the carbonyl group is elsewhere in the carbon skeleton, it is not reduced. 

In completely degassed nonpolar solvents such as hexane, pentane, and cyclohexane, no reaction apparently took place even on prolonged irradiation. On the other hand, in the presence of dissolved oxygen in the solvent, trace amounts of the photoproducts 86 and 87, formed by oxidation at the benzyhc carbon, were isolated. 

Comparison of the configuration of the stannane with the prodncts of reaction reveals that primary alkyl halides that are not benzyhc or a to a carbonyl react with inversion at the lithium-bearing carbon atom. In the piperidine series, the best data are for the 3-phenylpropyl compound, which was shown to be >99 1 er. In the pyrrolidine series, the er of the analogous compound indicates 21-22% retention and 78-79% inversion of configuration. Activated alkyl halides such as benzyl bromide and teri-butyl bromoacetate afford racemic adducts. In both the pyrrolidine and piperidine series, most carbonyl electrophiles (i.e. carbon dioxide, dimethyl carbonate, methyl chloroformate, pivaloyl chloride, cyclohexanone, acetone and benzaldehyde) react with virtually complete retention of configuration at the lithium-bearing carbon atom. The only exceptions are benzophenone, which affords racemic adduct, and pivaloyl chloride, which shows some inversion. The inversion observed with pivaloyl chloride may be due to partial racemization of the ketone product during work-up. 

In the patent literature, processes are described for the epimerization of the benzyhc chiral center at the 4-posihon using an alkoxide base [28] and for reagent-based dehydrogenation, then rehydrogenation, of the amine [29]. We envisaged racemization of the chiral amine center using the SCRAM catalyst and the tertiary carbon center using an alkoxide base (Scheme 13.10). 

I Secoiidarv alkvl halides Sk2 substitution occurs if a weakly basic nucleo-phile is used in a polar aprotic solvent, E2 elimination predominates if a strong base is used, and ElcB elimination takes place if the leaving group is two carbons away from a carbonyl group. Secondary allylic and benzyhc alkyl halides can also undergo Sjsjl and El reactions if a weakly basic nucleophile is used in a protic solvent. 

The Hammett p value of -4.1 suggests a carbocation intermediate as does the regioselectivity of the reaction (MeOH attacks the benzyhc position) but the stereochemistry (the reaction occurs with inversion) and a modest negative entropy of activation (AS = -48 JmoH K ) suggest rather an Sn2 reaction with a loose transition state having substantial positive charge at the benzylic carbon. Neither piece of evidence alone would be enough to define the mechanism. 

Reaction of TEMPO with [lr (TTP)(—CH2CH2CH2Ar)] species, desjnte the fact that these species also contain reactive benzyhc protons, only yields [(TTP)Ir Me]. This illustrates the importance of both the iridium center at the beta position and the arene at the alpha position to stabilize the carbon-centered... 

The greater the number of alkyl substituents bonded to the positively charged carbon, the more stable the carbocation will be. The order of relative stability of carbocations is tertiary benzyhc > allylic secondary > primary vinyl> phenyl. The nature of electron release by alkyl groups is not very clear. It may be an inductive effect, a resonance effect (hyperconjugation), or a combination of the two. When we refer to the inductive effect of the alkyl groups, it should be clear that this might well include a contribution from hyperconjugation. 

Several benzyhc cations have been obtained in solution as SbFg salts. Diaryl-methyl and triaryhnethyl cations are still more stable. Aryhnethyl cations are further stabihzed if they have electron-donating substituents in ortho or para positions. The stabihty of such cations can be further increased if electron-donating substituents feed into the it-system. Triaryknethyl cations are propeUer-shaped, even though the central carbon atom and the three ring carbons connected to it are in a plane. The three benzene rings cannot be all in the same plane because of steric hindrance. 

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