Alkylations with Alkyl Radicals

Tbbie 5.4. Alkylations with carbon-centered radicals. 

Examples of radical-mediated C-alkylations are listed in Table 5.4. In these examples, radicals are formed by halogen abstraction with tin radicals (Entries 1 and 2), by photolysis of Barton esters (Entry 3), and by the reduction of organomercury compounds (Entry 4). Carbohydrate-derived, polystyrene-bound a-haloesters undergo radical allylation with allyltributyltin with high diastereoselectivity (97% de [41]). Cleavage from supports by homolytic bond fission with simultaneous formation of C-H or C-C bonds is considered in Section 3.16. 

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The percentage of cyclohexylation is given in Fig. 1-20. (411,412). Hydrogen abstraction from the alkyl side-chain produces, in addition, secondary products resulting from the dimerization of thiazolylalkyl radicals or from their reaction with cyclohexyl radicals (Scheme 68) (411). 

The regioselectivity of addition of HBr to alkenes under normal (electrophilic addi tion) conditions is controlled by the tendency of a proton to add to the double bond so as to produce the more stable carbocatwn Under free radical conditions the regioselec tivity IS governed by addition of a bromine atom to give the more stable alkyl radical Free radical addition of hydrogen bromide to the double bond can also be initiated photochemically either with or without added peroxides... 

Following fragmentation the alkyl radical rapidly combines with a lithium atom to foim the oiganometalhc compound... 

As the temperature approaches the NTC zone, the reversibility of reaction 2 comes into play and the steady-state concentration of alkyl radicals rises. There is a competing irreversible reaction of oxygen with radicals containing an alpha hydrogen which produces a conjugate olefin (eq. 23). 

At the higher temperatures a decomposition of alkyl radicals, which is an olefin-producing variation of the -scission reaction, becomes competitive with reaction 23 (or sequence 2, 24) ... 

The extent of decarboxylation primarily depends on temperature, pressure, and the stabihty of the incipient R- radical. The more stable the R- radical, the faster and more extensive the decarboxylation. With many diacyl peroxides, decarboxylation and oxygen—oxygen bond scission occur simultaneously in the transition state. Acyloxy radicals are known to form initially only from diacetyl peroxide and from dibenzoyl peroxides (because of the relative instabihties of the corresponding methyl and phenyl radicals formed upon decarboxylation). Diacyl peroxides derived from non-a-branched carboxyhc acids, eg, dilauroyl peroxide, may also initially form acyloxy radical pairs however, these acyloxy radicals decarboxylate very rapidly and the initiating radicals are expected to be alkyl radicals. Diacyl peroxides are also susceptible to induced decompositions ... 

Alkylation of cyclohexane with isoprene can be carried out with alkyl radicals formed at 450°C and 20.3 MPa (200 atm) (73). 40% Pentenylcyclohexanes, 20% dipentenes (ie, substances having the general formula C qH ), and 40% higher boiling compounds are obtained using a 6.8 molar ratio of cyclohexane to isoprene and a space velocity of 2.5. Of the pentenylcyclohexanes, the head and tail products are in equal amounts. Even... 

Other compounds, eg, azoalkanes, acetone, etc, that yield alkyl radicals either thermally or by uv irradiation have been used with molecular oxygen to prepare alkyl hydroperoxides (r56). 

Polyamides, like other macromolecules, degrade as a result of mechanical stress either in the melt phase, in solution, or in the soHd state (124). Degradation in the fluid state is usually detected via a change in viscosity or molecular weight distribution (125). However, in the soHd state it is possible to observe the free radicals formed as a result of polymer chains breaking under the appHed stress. If the polymer is protected from oxygen, then alkyl radicals can be observed (126). However, if the sample is exposed to air then the radicals react with oxygen in a manner similar to thermo- and photooxidation. These reactions lead to the formation of microcracks, embrittlement, and fracture, which can eventually result in failure of the fiber, film, or plastic article. 

For monosubstituted alkylphenols, the position of the alkyl radical relative to the hydroxyl function is designated either with a numerical locant or ortho, meta, or para. The alkyl side chain typically retains a trivial name. Thus 4-(l,l,3,3-tetramethylbutyl)phenol, 4-/ f2 octylphenol, and para-tert-octy Tph.eno (PTOP) all refer to stmcture (1). 

Eor antioxidant activity, the reaction of aminyl radicals with peroxy radicals is very beneficial. The nitroxyl radicals formed in this reaction are extremely effective oxidation inhibitors. Nitroxides function by trapping chain-propagating alkyl radicals to give hydroxylamine ethers. These ethers, in turn, quench chain propagating peroxy radicals and in the process regenerate the original nitroxides. The cycHc nature of this process accounts for the superlative antioxidant activity of nitroxides (see Antioxidants). Thus, antioxidant activity improves with an increase in stabiUty of the aminyl and nitroxyl radicals. Consequendy, commercial DPA antioxidants are alkylated in the ortho and para positions to prevent undesirable coupling reactions. 

Initiation. Free-radical initiators are produced by several processes. The high temperatures and shearing stresses required for compounding, extmsion, and molding of polymeric materials can produce alkyl radicals by homolytic chain cleavage. Oxidatively sensitive substrates can react directly with oxygen, particularly at elevated temperatures, to yield radicals. 

The reaction rate of molecular oxygen with alkyl radicals to form peroxy radicals (eq. 5) is much higher than the reaction rate of peroxy radicals with a hydrogen atom of the substrate (eq. 6). The rate of the latter depends on the dissociation energies (Table 1) and the steric accessibiUty of the various carbon—hydrogen bonds it is an important factor in determining oxidative stabiUty. 

Termination. The conversion of peroxy and alkyl radicals to nonradical species terminates the propagation reactions, thus decreasing the kinetic chain length. Termination reactions (eqs. 7 and 8) are significant when the oxygen concentration is very low, as in polymers with thick cross-sections where the oxidation rate is controlled by the diffusion of oxygen, or in a closed extmder. The combination of alkyl radicals (eq. 7) leads to cross-linking, which causes an undesirable increase in melt viscosity. 

The effect substitution on the phenolic ring has on activity has been the subject of several studies (11—13). Hindering the phenolic hydroxyl group with at least one bulky alkyl group ia the ortho position appears necessary for high antioxidant activity. Neatly all commercial antioxidants are hindered ia this manner. Steric hindrance decreases the ability of a phenoxyl radical to abstract a hydrogen atom from the substrate and thus produces an alkyl radical (14) capable of initiating oxidation (eq. 18). 

Lumped mechanisms are based on the grouping of chemical compounds into classes of similar stmcture and reactivity. For example, all alkanes might be lumped into a single class, the reaction rates and products of which are based on a weighted average of the properties of all the alkanes present. For example, as shown in Table 1, the various alkanes, CH2 2 > react with OH in a similar manner to form alkyl radicals,. When expressed... 

Esters are named by replacing the ending -ic acid with the suffix -ate. The alcohol portion of the ester is named by replacing the -ane ending of the parent hydrocarbon name with the suffix -yl. The alkyl radical name of an ester is separated from the carboxylate name, eg, methyl formate for HCOOCH. Amides are named by changing the ending -oic acid to -amide for either systematic or common names, eg, hexanamide and acetamide. 

An interesting method for the substitution of a hydrogen atom in rr-electron deficient heterocycles was reported some years ago, in the possibility of homolytic aromatic displacement (74AHC(16)123). The nucleophilic character of radicals and the important role of polar factors in this type of substitution are the essentials for a successful reaction with six-membered nitrogen heterocycles in general. No paper has yet been published describing homolytic substitution reactions of pteridines with nucleophilic radicals such as alkyl, carbamoyl, a-oxyalkyl and a-A-alkyl radicals or with amino radical cations. 

It is estimated that thiophene reacts with phenyl radicals approximately three times as fast as benzene. Intramolecular radical attack on furan and thiophene rings occurs when oxime derivatives of type (112) are treated with persulfate (8UCS(Pt)984). It has been found that intramolecular homolytic alkylation occurs with equal facility at the 2- and 3-positions of the thiophene nucleus whereas intermolecular homolytic substitution occurs mainly at position 2. 

Alkyl radicals produced by oxidative decarboxylation of carboxylic acids are nucleophilic and attack protonated azoles at the most electron-deficient sites. Thus imidazole and 1-alkylimidazoles are alkylated exclusively at the 2-position (80AHC(27)241). Similarly, thiazoles are attacked in acidic media by methyl and propyl radicals to give 2-substituted derivatives in moderate yields, with smaller amounts of 5-substitution. These reactions have been reviewed (74AHC(i6)123) the mechanism involves an intermediate cr-complex. 

Relationships connecting stmcture and properties of primary alkylamines of normal stmcture C, -C gin chloroform and other solvents with their ability to extract Rh(III) and Ru(III) HCA from chloride solutions have been studied. The out-sphere mechanism of extraction and composition of extracted associates has been ascertained by UV-VIS-, IR-, and H-NMR spectroscopy, saturation method, and analysis of organic phase. Tertiary alkylamines i.e. tri-n-octylamine, tribenzylamine do not extract Ru(III) and Rh(III) HCA. The decrease of radical volume of tertiary alkylamines by changing of two alkyl radicals to methyl make it possible to diminish steric effects and to use tertiary alkylamines with different radicals such as dimethyl-n-dodecylamine which has not been used previously for the extraction of Rh(III), Ru(III) HCA with localized charge. 

Alkyl radicals, R, react very rapidly with O2 to form alkylperoxy radicals. H reacts to form the hydroperoxy radical HO2. Alkoxy radicals, RO, react with O2 to form HO2 and R CHO, where R contains one less carbon. This formation of an aldehyde from an alkoxy radical ultimately leads to the process of hydrocarbon chain shortening or clipping upon subsequent reaction of the aldehyde. This aldehyde can undergo photodecomposition forming R, H, and CO or, after OH attack, forming CH(0)00, the peroxyacyi radical. 

Entry 3 has only alkyl substituents and yet has a significant lifetime in the absence of oxygen. The tris(/-butyl)methyl radical has an even longer lifetime, with a half-life of about 20 min at 25°C. The steric hindrance provided by the /-butyl substituents greatly retards the rates of dimerization and disproportionation of these radicals. They remain highly reactive toward oxygen, however. The term persistent radicals is used to describe these species, because their extended lifetimes have more to do with kinetic factors than with inherent stability." Entry 5 is a sterically hindered perfluorinated radical and is even more long-lived than similar alkyl radicals. 

The broad conclusion of all these studies is that alkyl radicals are shallow pyramids and that the barrier to inversion of the pyramidal structures is low. Radicals also are able to tolerate some geometric distortion associated with strained ring systems. 

Simple alkyl radicals such as methyl are considered to be nonnucleophilic. Methyl radicals are somewhat more reactive toward alkenes bearing electron-withdrawing substituents than towards those with electron-releasing substituents. However, much of this effect can be attributed to the stabilizing effect that these substiments have on the product radical. There is a strong correlation of reaction rate with the overall exothermicity of the reaction. Hydroxymethyl and 2-hydroxy-2-propyl radicals show nucleophilic character. The hydroxymethyl radical shows a slightly enhanced reactivity toward acrylonitrile and acrolein, but a sharply decreased reactivity toward ethyl vinyl ether. Table 12.9 gives some of the reactivity data. 

A chain mechanism is proposed for this reaction. The first step is oxidation of a carboxylate ion coordinated to Pb(IV), with formation of alkyl radical, carbon dioxide, and Pb(III). The alkyl radical then abstracts halogen from a Pb(IV) complex, generating a Pb(IIl) species that decomposes to Pb(II) and an alkyl radical. This alkyl radical can continue the chain process. The step involving abstraction of halide from a complex with a change in metal-ion oxidation state is a ligand-transfer type reaction. 

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