Halogen-substituted Alkyl Radicals

Chemical Properties.—Chemically the ethers are not very active nor do they lead to important derivatives. Chlorine forms substitution products in which, as in methyl ether, one to six hydrogens of the alkyl radicals are substituted. The halogen acids, especially hydriodic acid, form an alcohol by a reaction analogous to the reversion of the Williamson synthesis. 

D. J. Edge and J. K. Kochi, Effects of halogen substitution on alkyl radicals conformational studies by electron spin resonance. J. Am. Chem. Soc. 94(18), 6485-6495 (1972). 

Several reactions of halogen-substituted carbon-centered radicals with silanes have been studied, but limited kinetic information is available for reactions of halogen-substituted radicals with tin hydrides. A rate constant for reaction of the perfluorooctyl radical with Bu3SnH was determined by competition against addition of this radical to styrenes, reactions that were calibrated directly by LFP methods.93 At ambient temperature, the n-C8F17 radical reacts with tin hydride two orders of magnitude faster than does an alkyl radical, consistent with the electron-deficient nature of the perflu-oroalkyl radical and the electron-rich character of the tin hydride. Similar behavior was noted previously for reactions of silanes with perhaloalkyl radicals. 

The possibility that substitution results from halogen-atom transfer to the nucleophile, thus generating an alkyl radical that could then couple with its reduced or oxidized form, has been mentioned earlier in the reaction of iron(i) and iron(o) porphyrins with aliphatic halides. This mechanism has been extensively investigated in two cases, namely the oxidative addition of various aliphatic and benzylic halides to cobalt(n) and chromiumfn) complexes. 

This procedure has been used to prepare a variety of substituted a-bromohydrocinnamic acids 2 p-acetyl-a-bromohydro-cinnamic acid was prepared for the first time by this method. The method illustrates a typical application of the Meerwein reaction for the arylation of unsaturated substrates.3 In this reaction a catalytic amount of a copper(I) salt is used to reduce an aryl diazonium salt forming an aryl radical and a copper(II) halide. Addition of the aryl radical to an unsaturated substrate forms an alkyl radical that is reoxidized by the copper(II) halide present forming an alkyl halide and regenerating the copper(I) salt catalyst. In this preparation, the product, an a-bromo acid, is formed in an acidic reaction mixture and dehydro-halogenation does not occur. However, dehydrohalogenation... 

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. 

Numerous derivatives of (1) have been thus prepared, notably 2,3-dimethyl (or dialkyl)benzofurans Bz-substituted by alkyl radicals,36,213-218 methoxyl groups,101,219-221 halogen atoms,217,222-224 aryl groups,225 acetyl groups,215,218,226 formyl groups,222,226 and carboxyl groups.226,227 The method is especially valuable in the case of formyl derivatives, which are difficult to obtain otherwise. 

The substitution path b) (Eq. (94) ), is favored by the following experimental conditions low current density, grapliite as anode material, alkaline medium, water or water-pyridine as solvent, and admixture of foreign ions e.g., bicarbonate, sulfate, perchlorate, dihydrogen phosphate, Pb2+, Mn2+, Cu2+, Fe2+, Co2+. The carbonium ion path b) can furthermore be expected for carboxylates RR CHOO with a-substituents R such as alkyl, phenyl 198 hydroxy, halogen 1 amino, or alkoxy. These substituents facilitate oxidation of the intermediate alkyl radical R to the carbonium ion R+. Product formation occurs via carbonium ions and not, as is also conceivable, via mixed coupling of R with Nu ... 

One of us, as well as Bottoni, recently investigated homolytic substitution reactions of silyl radicals at the halogen atom of halomethanes (CH3X, X = Cl, Br, I), and the chalcogen atom in methanechalcogenols (CH3EH, E = S, Se, Te) and alkyltellurols, with expulsion of alkyl radical (equations 12 and 13)40-43. 

Although we discussed its mechanism at length in Section 4-3, free-radical halogenation is rarely an effective method for the synthesis of alkyl halides. It usually produces mixtures of products because there are different kinds of hydrogen atoms that can be abstracted. Also, more than one halogen atom may react, giving multiple substitutions. For example, the chlorination of propane can give a messy mixture of products. 

Derivatives of lysergic acid or dihydrolysergic acid, in which the 1 position is free or substituted with an alkyl radical, may be halogenated in the 2 position with bromino- or iodosuccinimide, X-2,6-trichloro-4-nitroacetanilide, and similar mild reagents (157) to compounds LXIX, a-c. 

Alkyl.—The general name for a radical of this series is alkyl. A halogen alkyl or alkyl halide is thus a halogen substitution product of any paraffin hydrocarbon, or it is composed of a paraffin or alkyl radical linked to a halogen atom. The general formula for an alkyl radical is (CnH2 +i). 

Hydroxyl Substitution Products.— All of the preceding facts lead to the conclusion that alcohol is a compound in which the ethyl radical is linked to the hydroxyl radicalj i.e, it is the hydroxyl substiltUion product of ethane or hydroxy ethane. Alcohols thus belong to the same general class of compounds as the halogen substitution products. The relationship between the hydrocarbons, the halogen substitution products, alkyl halides and the hydroxyl substitution products, alcohols, may be shown as follows ... 

Allyl Chloride.—The halogen substitution products of propene and the higher hydrocarbons of the ethene series, when the substitution is in a carbon group not doubly linked, are of importance in the synthesis of derivatives in the same way as are the alkyl halides. 3-Chlor propene or propenyl chloride, CH2 = CH—CH2CI, is known also as allyl chloride, the radical (CH2 = CH—CH2—) being known as allyl. 

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