Radicals substitution reactions

The free radical mechanism is confirmed by the fact that if a substituted aromatic hydrocarbon is used in this reaction, the incoming group (derived from the diazotate) may not necessarily occupy the position in the benzene ring normally determined by the substituent present—a characteristic of free radical reactions. 

As is broadly true for aromatic compounds, the a- or benzylic position of alkyl substituents exhibits special reactivity. This includes susceptibility to radical reactions, because of the. stabilization provided the radical intermediates. In indole derivatives, the reactivity of a-substituents towards nucleophilic substitution is greatly enhanced by participation of the indole nitrogen. This effect is strongest at C3, but is also present at C2 and to some extent in the carbocyclic ring. The effect is enhanced by N-deprotonation. 

For most vinyl polymers, head-to-tail addition is the dominant mode of addition. Variations from this generalization become more common for polymerizations which are carried out at higher temperatures. Head-to-head addition is also somewhat more abundant in the case of halogenated monomers such as vinyl chloride. The preponderance of head-to-tail additions is understood to arise from a combination of resonance and steric effects. In many cases the ionic or free-radical reaction center occurs at the substituted carbon due to the possibility of resonance stabilization or electron delocalization through the substituent group. Head-to-tail attachment is also sterically favored, since the substituent groups on successive repeat units are separated by a methylene... 

Substitution Reactions. Substitution reactions can occur on the methyl group by free-radical attack. The abstraction of an aHybc hydrogen is the most favored reaction, followed by addition to that position. 

Substitution Reactions on the Methyl Group. The reactions that give substitution on the methyl group are generally high temperature and free-radical reactions. Thus, chlorination at ca 100°C, or in the presence of ultraviolet light and other free-radical initiators, successively gives benzyl chloride, benzal chloride, and benzotrichloride. 

This reaction proceeds through a chain mechanism. Free-radical additions to 1-butene, as in the case of HBr, RSH, and H2S to other olefins (19—21), can be expected to yield terminally substituted derivatives. Some polymerization reactions are also free-radical reactions. 

The use of free-radical reactions for this mode of ring formation has received rather more attention. The preparation of benzo[Z)]thiophenes by pyrolysis of styryl sulfoxides or styryl sulfides undoubtedly proceeds via formation of styrylthiyl radicals and their subsequent intramolecular substitution (Scheme 18a) (75CC704). An analogous example involving an amino radical is provided by the conversion of iV-chloro-iV-methylphenylethylamine to iV-methylindoline on treatment with iron(II) sulfate in concentrated sulfuric acid (Scheme 18b)(66TL2531). 

Pyrido[3,4-d]pyrimidine-2,4-dione synthesis, 3, 215 Pyridopyrimidines, 3, 201 iV-alkylations, 3, 206 biological activity, 3, 260-261 1-electron reductions, 3, 207 IR spectra, 3, 204 mass spectra, 3, 204 MO calculations, 3, 204 NMR, 3, 202, 203 nucleophilic substitution, 3, 213 8-nucleosides synthesis, 3, 206 physical properties, 3, 201-205 protonation, 3, 206 radical reactions, 3, 215 reactions with water, 3, 207 reduced... 

Table 12.9. Absolute Rates of Addition Reactions of Methyl, Cyanomethyl, and Hydrosymethyl Radicals toward Substituted Aikenes, CHi=CHX...

Mixed aryl selenides have also proven to be excellent ree ents for group transfer reactions.Photolysis of selenides in an inert solvent such as benzene can initiate chain reactions. Substituted radicals can be generated in this manner, from a-selenoe-... 

The first three chapters discuss fundamental bonding theory, stereochemistry, and conformation, respectively. Chapter 4 discusses the means of study and description of reaction mechanisms. Chapter 9 focuses on aromaticity and aromatic stabilization and can be used at an earlier stage of a course if an instructor desires to do so. The other chapters discuss specific mechanistic types, including nucleophilic substitution, polar additions and eliminations, carbon acids and enolates, carbonyl chemistry, aromatic substitution, concerted reactions, free-radical reactions, and photochemistry. 

The course of each of the free radical reactions shown in equations 19-21, where fluorine substitution alters the normal trans stereochemistry of addition, is ascnbed to endo fluonne stenc effects... 

Substituted pyrazolin-5-ones have only three and -substituted pyrazolin-3-ones only two tautomers, since now the corresponding 19c and 19d structures are isomers. The calculations involved l-methylpyrazolin-5-one (PM3/6-3H-G, anions and cations), l-phenyl-3-methyl-2-pyrazolin-5-one (DFT, radical reactions) [97JPC(A)3769], and l-(2, 4 -dinitrophenyl)-3-methyl-2-pyrazolin-5-one [B3LYP/6-31G and the crystal structure (Section V,D,2)] (98NJC1421). 

The reactivity of pyridine relative to that of benzene has been measured using the competitive technique developed by Ingold and his schoool for corresponding studies of electrophilic aromatic substitution. The validity of the method applied to free-radical reactions has been discussed. Three sources of the phenyl radical have been used the results obtained are set out in Table II. 

A second theoretical index, and one for which there appears to be more justification in its application to free-radical reactions, is the atom localization energy. This index is a measure of the energy required to localize one electron of the 7r-electron system in the aromatic molecule at the point of attack of the radical. The formation of the intermediate adduct in a free-radical aromatic substitution may be regarded as the sum of two processes one, the localization of an electron at the point of attack and the other, the pairing of this... 

The chlorination of toluene by substituting the methyl hydrogens is a free radical reaction. A mixture of three chlorides (benzyl chloride, ben-zal chloride and benzotrichloride) results. 

As an example of an industrially useful radical reaction, look at the chlorination of methane to yield chloromethane. This substitution reaction is the first step in the preparation of the solvents dichloromethane (CHoCl ) and chloroform (CHCI3). 

Claisen rearrangement, 1194-1195 dehydration, 622 elimination reactions, 393 oxidation, 625-626 radical reactions, 243-244 characteristics of, 162-164 comparison with laboratory reactions, 162-164 conventions for writing, 162. 190 energy diagram of, 161 reduction, 723-725 reductive animation, 932 substitution reactions, 381-383 Biological reduction, NADH and, 610-611... 

Direct perfluoroalkylation of heteroaromatics occurs with RFI when sodium hydroxymethane sulfinate (Rongalite) is present. 3-Perfluoroal-kylcoumarins can be obtained (90CC1781). The distribution of isomers from substituted pyridines is compatible with a radical reaction (90TL2711). 

Most radicals are transient species. They (e.%. 1-10) decay by self-reaction with rates at or close to the diffusion-controlled limit (Section 1.4). This situation also pertains in conventional radical polymerization. Certain radicals, however, have thermodynamic stability, kinetic stability (persistence) or both that is conferred by appropriate substitution. Some well-known examples of stable radicals are diphenylpicrylhydrazyl (DPPH), nitroxides such as 2,2,6,6-tetramethylpiperidin-A -oxyl (TEMPO), triphenylniethyl radical (13) and galvinoxyl (14). Some examples of carbon-centered radicals which are persistent but which do not have intrinsic thermodynamic stability are shown in Section 1.4.3.2. These radicals (DPPH, TEMPO, 13, 14) are comparatively stable in isolation as solids or in solution and either do not react or react very slowly with compounds usually thought of as substrates for radical reactions. They may, nonetheless, react with less stable radicals at close to diffusion controlled rates. In polymer synthesis these species find use as inhibitors (to stabilize monomers against polymerization or to quench radical reactions - Section 5,3.1) and as reversible termination agents (in living radical polymerization - Section 9.3). 

Outcomes from the reactions of radicals with substituted acrylate esters depend on the attacking radical (refer Table 1.3 and Scheme 1.4). The results may be summarized as follows (the methyl substituent is usually considered to be electron donating - Section 1.2.2) ... 

The traditional means of assessment of the sensitivity of radical reactions to polar factors and establishing the electrophilicity or nucleophilieity of radicals is by way of a Hammett op correlation. Thus, the reactions of radicals with substituted styrene derivatives have been examined to demonstrate that simple alkyl radicals have nucleophilic character38,39 while haloalkyl radicals40 and oxygcn-ccntcrcd radicals " have electrophilic character (Tabic 1.4). It is anticipated that electron-withdrawing substituents (e.g. Cl, F, C02R, CN) will enhance overall reactivity towards nucleophilic radicals and reduce reactivity towards electrophilic radicals. Electron-donating substituents (alkyl) will have the opposite effect. 

Thiols react more rapidly with nucleophilic radicals than with electrophilic radicals. They have very large Ctr with S and VAc, but near ideal transfer constants (C - 1.0) with acrylic monomers (Table 6.2). Aromatic thiols have higher C,r than aliphatic thiols but also give more retardation. This is a consequence of the poor reinitiation efficiency shown by the phenylthiyl radical. The substitution pattern of the alkanethiol appears to have only a small (<2-fokl) effect on the transfer constant. Studies on the reactions of small alkyl radicals with thiols indicate that the rate of the transfer reaction is accelerated in polar solvents and, in particular, water.5 Similar trends arc observed for transfer to 1 in S polymerization with Clr = 1.4 in benzene 3.6 in CUT and 6.1 in 5% aqueous CifiCN.1 In copolymerizations, the thiyl radicals react preferentially with electron-rich monomers (Section 3.4.3.2). 

Besides radical additions to unsaturated C—C bonds (Section III.B.l) and sulfene reactions (see above), sulfonyl halides are able to furnish sulfones by nucleophilic substitution of halide by appropriate C-nucleophiles. Undesired radical reactions are suppressed by avoiding heat, irradiation, radical initiators, transition-element ion catalysis, and unsuitable halogens. However, a second type of undesired reaction can occur by transfer of halogen instead of sulfonyl groups283-286 (which becomes the main reaction, e.g. with sulfuryl chloride). Normally, both types of undesired side-reaction can be avoided by utilizing sulfonyl fluorides. 

This allyl transfer reaction, which is a valuable synthetic method, has been shown to be a free-radical chain substitution (SH2 ), namely... 

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