Radical aromatic substitution relative rates

The competitive method employed for determining relative rates of substitution in homolytic phenylation cannot be applied for methylation because of the high reactivity of the primary reaction products toward free methyl radicals. Szwarc and his co-workers, however, developed a technique for measuring the relative rates of addition of methyl radicals to aromatic and heteroaromatic systems. - In the decomposition of acetyl peroxide in isooctane the most important reaction is the formation of methane by the abstraction of hydrogen atoms from the solvent by methyl radicals. When an aromatic compound is added to this system it competes with the solvent for methyl radicals, Eqs, (28) and (29). Reaction (28) results in a decrease in the amount... 

Products isolated from the thermal fragmentation of A-arylbenzamide oximes and A-arylbenzamide O-phenylsulfonyl oximes have been accounted for by invoking a free-radical mechanism which is initiated by the preferential homolysis of the N-O bond." Time-resolved IR spectroscopy has revealed that photolysis of A, A -diphenyl-l,5-dihydroxy-9,10-anthraquinone diimine affords acridine-condensed aromatic products via excited-state intramolecular proton transfer." The absolute and relative rates of thermal rearrangements of substituted benzyl isocyanides have been measured,and it has been found that the relative rates are independent of temperature and exhibit excellent Hammett correlations. Thionitrosoarene (25), thought to be generated by desulfurization of the stable A-thiosulfinylaniline (24), has been established" " as an intermediate in the formation of 3,3a-dihydro-2,l-benzisothiazole (26) from o-alkylthionitrosoarene (24). 

One of the solvated electrons is transferred into an antibonding 7t -orbital of the aromatic compound, and a radical anion of type C is formed (Figure 17.82). The alcohol protonates this radical anion in the rate-determining step with high regioselectivity. In the case under scrutiny, and starting from other donor-substituted benzenes as well, the protonation occurs in the ortho position relative to the donor substituent. On the other hand, the protonation of the radical anion intermediate of the Birch reduction of acceptor-substituted benzenes occurs in the para-position relative to the acceptor substituent. 

In Table 19, the relative rates, obtained in the alkylation of 3-substituted pyridines by f-butyl radical, are reported. The exceptional positional selectivity (only the position 6 is attacked) results from combined polar and steric effects. A satisfying Hammett correlation was observed with Op the value of p = 5.5 is of the same order of magnitude of those of nucleophilic aromatic substitutions, indicating a high degree of charge development in the transition state. 

The relative ratio of tail, head, and aromatic addition was determined by decomposing benzoyl peroxide (BPO) in styrene containing the radical trapping agent 1 (Scheme 12) [148]. The tail addition product 9a accounted for of the benzoyloxy derived products while the head addition 11a only accounted for 5%. Aromatic substitution products 13a accounted for the other 15% of the benzoyloxy radicals. The ratio of these products was however somewhat dependant upon the concentration of 1. This is likely due to the relative rates of addition to styrene and of 1 to benzyl radical 8a and primary alkyl radical 10a. 

Proposals for the mechanism of PPS formation include nucleophilic aromatic substitution (Sj Ar) (2radical-cation (27), and radical-anion processes (28,29). Some of the interesting features of the polymerization are that the initial reaction of the sodium sulfide-hydrate with NMP affords a soluble NaSH-sodium 4-(N-methylamino)butanoate mixture, and that polymers of higher molecular weight than pi edicted by the Caruthers equation are produced at low conversions. Mechanistic elucidation has been hampered by the harsh polymerization conditions and poor solubility of PPS in common organic solvents. A detailed mechanistic study of model compounds by Fahey provided strong evidence that the ionic S]s Ar mechanism predominates (30). Some of the evidence supporting the S s(Ar mechanism was the selective formation of phenylthiobenzenes, absence of disulfide production, kinetics behavior, the lack of influence of radical initiators and inhibitors, relative rate Hammet values, and activation parameters consistent with nucleophilic aromatic substitution. The radical-anion process was not completely discounted and may be a minor competing mechanism. 

Such nucleophilic displacements are likely to be addition-elimination reactions, whether or not radical anions are also interposed as intermediates. The addition of methoxide ion to 2-nitrofuran in methanol or dimethyl sulfoxide affords a deep red salt of the anion 69 PMR shows the 5-proton has the greatest upfield shift, the 3- and 4-protons remaining vinylic in type.18 7 The similar additions in the thiophene series are less complete, presumably because oxygen is relatively electronegative and the furan aromaticity relatively low. Additional electronegative substituents increase the rate of addition and a second nitro group makes it necessary to use stopped flow techniques of rate measurement.141 In contrast, one acyl group (benzoyl or carboxy) does not stabilize an addition product and seldom promotes nucleophilic substitution by weaker nucleophiles such as ammonia. Whereas... 

The fact that such selectivity was not found with homolytic alkylation of nonprotonated heteroaromatics (Table I) or with homocyclic aromatics indicates that polar factors play a major role in the reactivity of alkyl radicals with protonated bases. These effects were determined by the study of the relative reaction rates in the alkylation of 4-substituted pyridines in acidic medium. The results obtained with methyl, n-propyl, w-butyl, sec-butyl, i-butyl, and benzyl radicals are summarized in Table III. 

Nitro-substituted phenyl halides produce radical anions that fragment with a rather low rate (=10 2-102/s) [28]. For this reason the nitro group is not a suitable substituent for most aromatic SrnI reactions. However, exceptions are found with o-iodonitrobenzene [29] whose radical anion has a relatively high rate of fragmentation, and nitroaryldiazo phenyl or tert-butyl sulfides [30]. 

Several methods have been employed to determine the rate constant of the addition of nucleophiles to radicals. Relative reactivities of pairs of nucleophiles toward the same radical have been obtained from the ratio of the two substitution products14. The absolute value of the rate constant for the coupling of aromatic radicals with nucleophiles has been determined by cyclic voltammetry. A large number of these values are close to the diffusion limit15. 

Decarboxylation of excited singlets of aromatic esters (Eq. 13.6) is a concerted process, and it can account for a significant fraction of the reaction by appropriately substituted aryl esters, especially in bulk polymers and other media that are capable of imposing conformational constraints on guest molecules.Because photoinduced decarboxylation occurs before lysis of the aryl esters, it does not influence the rates at which the A B singlet pair react. For that reason, the relative yields of decarboxylation products need not be considered in analyses of the radical pairs unless their formation precludes sufficient radical pair production for their easy direct or indirect detection. 

Dithianes and gemdithioacetals could be alternatively oxidized indirectly by means of the redox catalysis method. The technique appeared to be particularly mild and mainly avoided inhibition and adsorption phenomena relative to the anode platinum interface. Thus aromatic hydrocarbons (e.g. 9,10-diphenylanthracene) [83] and judiciously substituted triphenylamines [84] afford quite stable cation radicals used homogeneously as oxidants. Their standard potential, E°x, will determine the rate of electron exchange with the concerned sulfur compound. The cleavage of a C—S bond in any dithiane can be regarded as fast enough to draw the redox catalysis process to the indirect oxidation. 

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