4- phenyl-, radical substitution

Qualitatively, the results shown in Tables IV and V indicate that the methyl radical, just as the phenyl radical, substitutes pyridine preferentially in the 2- and 4-positions. The absence of the 3-isomer in these reactions is probably a result of the method of analysis... 

The hydrogenation rate of olefins on Pt falls as the extent of the hydrogen substitution at the double bond by alkyl groups increases [Lebedev s rule (418)-, as the number of phenyl radicals substituting the alkyl radicals at the double bond in olefins increases the rate of hydrogenation on Pt decreases 419)]. 

In the case of substituted aryl radicals, the results may be slightly different, depending on the polarity of the radicals. With electrophilic radicals the overall reactivity of the thiazole nucleus will decrease and the percentage of 5-substituted isomer (electron-rich position) will increase, in comparison with phenyl radicals. The results are indicated in Table III-28. 

The thiazolyl radicals are, in comparison to the phenyl radical, electrophilic as shown by isomer ratios obtained in reaction with different aromatic and heteroaromatic compounds. Sources of thiazolyl radicals are few the corresponding peroxide and 2-thiazolylhydrazine (202, 209, 210) (see Table III-34) are convenient reagents, and it is the reaction of an alky] nitrite (jsoamyl) on the corresponding (2-, 4-, or 5-) amine that is most commonly used to produce thiazolyl radicals (203-206). The yields of substituted thiazole are around 40%. These results are summarized in Tables III-35 and IIT36. 

Radicals derived from monocyclic substituted aromatic hydrocarbons and having the free valence at a ring atom (numbered 1) are named phenyl (for benzene as parent, since benzyl is used for the radical C5H5CH2—), cumenyl, mesityl, tolyl, and xylyl. All other radicals are named as substituted phenyl radicals. For radicals having a single free valence in the side chain, these trivial names are retained ... 

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. 

Phenyl radicals attack azoles unselectively to form a mixture of phenylated products. Relative rates and partial rate factors are given in Table 7. The phenyl radicals may be prepared from the usual precursors PhN(NO)COMe, Pb(OCOPh)4, (PhC02)2 or PhI(OCOPh)2. Substituted phenyl radicals react similarly. 

In Volume 2, in the chapter on Free-Radical Substitutions of Heteroaromatic Compounds by R. O. C. Norman and G. K. Radda, p. 166, Table VI, 6-R-Acridine should read 9-R-Acridine p. 167, lines 17 and 18, 6-phenylacridine should read 9-phenyl-acridine... 

Dimesitylimidazolium chloride with chromocene gives the carbene 32 (R = C1) (990M529). With phenylmagnesium chloride, 32 (R = C1) gives 32 (R = Ph), the product of substitution of the chloride ligand by phenyl radical. In chloroform, 32 (R = C1) gives the chromium(III) species 33. In contrast,... 

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. 

There is an early report that thiophene reacts at the 3-position in phenylation with benzenediazonium chloride and aluminum trichloride, but in the Gomberg reaction thiophene has been found to substitute mainly at the 2-position both with p-tolyl and with p-chloro-phenyl radicals.Bcnzothiazole is phenylated at the 2-position in low yield by dibenzoyl peroxide a small quantity of the 4-isomcr is also obtained. ... 

For reactions with S, specificity is found to decrease in the series cyanoisopropyl mcthyl Fbutoxy>phcnyl>bcnzoyloxy. Cyanoisopropyl (Scheme 3.3),7 f-bntoxy and methyl radicals give exclusively tail addition. Phenyl radicals afford tail addition and ca l% aromatic substitution. Benzoyloxy radicals give tail addition, head addition, and aromatic substitution (Scheme 3.4). ... 

Peroxide decomposition in aromatic and other unsaturated solvents homolytic aroniMic substitution and olefin polymerization Decomposition of peroxides in aromatic solvents leads to attack on the aromatic nucleus by radicals and hence to substitution products (for a recent summary, see Williams, 1970). In the substitution of benzene and related substrates by phenyl radicals, for example, cyclohexadienyl... 

Some radicals (e.g., tert-butyl, benzyl, and cyclopropyl), are nucleophilic (they tend to abstract electron-poor hydrogen atoms). The phenyl radical appears to have a very small degree of nucleophilic character. " For longer chains, the field effect continues, and the P position is also deactivated to attack by halogen, though much less so than the a position. We have already mentioned (p. 896) that abstraction of an a hydrogen atom from ring-substituted toluenes can be correlated by the Hammett equation. 

TABLE 14.2 Partial Rate Factors for Attack of Substituted Benzenes by Phenyl Radicals Generated from BZ2O2 (Reaction 14-21)... 

The strained hydrocarbon [1,1,1] propellane is of special interest because of the thermodynamic and kinetic ease of addition of free radicals (R ) to it. The resulting R-substituted [ 1.1.1]pent-1-yl radicals (Eq. 3, Scheme 26) have attracted attention because of their highly pyramidal structure and consequent potentially increased reactivity. R-substituted [1.1.1]pent-1-yl radicals have a propensity to bond to three-coordinate phosphorus that is greater than that of a primary alkyl radical and similar to that of phenyl radicals. They can add irreversibly to phosphines or alkylphosphinites to afford new alkylphosphonites or alkylphosphonates via radical chain processes (Scheme 26) [63]. The high propensity of a R-substituted [1.1.1] pent-1-yl radical to react with three-coordinate phosphorus molecules reflects its highly pyramidal structure, which is accompanied by the increased s-character of its SOMO orbital and the strength of the P-C bond in the intermediate phosphoranyl radical. 

The same strategy has recently been used in the quite challenging determination of the standard potentials for the reduction of phenyl and substituted phenyl radicals.48 In this case the radical is so easy to reduce that starting from iodides was not sufficient. One had to go to the very reducible phenyl diazonium cations to see the wave of the radical appear beyond the radical-producing wave. 

The phenylselenyl radical adds irreversibly to the central carbon atom of 2-methylbuta-l, 2-diene (Id) with a rate constant of 3 x 106 M-1 s-1 (23 1 °C) (Scheme 11.7) [45], On a synthetic scale, PhSe addition to cumulated Jt-bonds has been investigated by oxidizing phenylselenol with air in the presence of mono-, 1,1-di- or 1,3-di-substituted allenes to provide products of selective fi-addition. Trapping of 2-phenyl -selenyl-substituted allyl radicals with 02 did not interfere with the hydrogen atom delivery from PhSeH (Scheme 11.7) [31]. 

As evident from Scheme 4.9, one-electron oxidation of 1,4-dimethoxybenzene produces cation-radical. The cation-radical, being more active than the initial substrate, recombines with benzoyloxy radical before the latter decomposes into phenyl radical and carbon dioxide. The process ends in the formation of a stable substitution product. 

The reaction of Scheme 4.10 yields only products of ortho and para substitutions the meta isomer is lacking. If it were a standard radical substitution, the meta-isomer would obviously be formed in a certain amount (i.e., in the same amount as that for ortho-substituted product). Introduction of electron-acceptor substituents enhances stability of the substrate to oxidation and prevents electron transfer to benzoyloxy radical. As a result, phenylation takes place instead of benzoyloxylation, and the phenyl radical enters into any free position. 

Pinson and Saveant 1978, Swartz and Stenzel 1984). On electrochemical initiation (Hg cathode), 4-bromobenzophenone gives rise to 4-(phenylthio)benzophenone in the 80% yield, whereas bromoben-zene yields diphenyldisulfide with the yield of only 10% and unsubstituted benzene with the yield of more than 95%. In the bromobenzene case, this means that the substitution is a minor reaction, whereas the main ronte is ordinary debromination. According to Swartz and Stenzel (1984), the substrate anion-radicals are initially formed in the preelectrode space. Stability of these anion-radicals are different. The less stable anion-radicals of bromobenzene do not have enough time to go into the catholyte pool. They give rise to the phenyl radicals in the vicinity of the cathode. The phenyl radicals are instantly reduced into the phenyl anions. They tear protons from the solvent and yield benzene. 

Swartz and Stenzel (1984) proposed an approach to widen the applicability of the cathode initiation of the nucleophilic substitution, by using a catalyst to facilitate one-electron transfer. Thus, in the presence of PhCN, the cathode-initiated reaction between PhBr and Bu4NSPh leads to diphe-nydisulfide in such a manner that the yield increases from 10 to 70%. Benzonitrile captures an electron and diffuses into the pool where it meets bromobenzene. The latter is converted into the anion-radical. The next reaction consists of the generation of the phenyl radical, with the elimination of the bromide ion. Since generation of the phenyl radical takes place far from the electrode, this radical is attacked with the anion of thiophenol faster than it is reduced to the phenyl anion. As a result, instead of debromination, substitution develops in its chain variant. In other words, the problem is to choose a catalyst such that it would be reduced more easily than a substrate. Of course, the catalyst anion-radical should not decay spontaneously in a solution. 

The rate of an electron transfer from the reduced catalyst to the substrate is also important. If the rate is excessively high, the electron exchange will occur within the preelectrode space and the catalytic effect will not be achieved. If the rate is excessively low, a very high concentration of the catalyst will be needed. However, at high concentration, the anion-radicals of the catalyst will reduce the phenyl radicals. Naturally, this will be unfavorable for the chain process of the substitution. As catalysts, substances that can be reduced at potentials by 50 mV less negative than those of the substrates should be chosen. The optimal concentration of the catalyst must be an order lower than that of a substrate (Swartz and Stenzel 1984). 

Another type of semisynthetic penicillin that should undoubtedly be considered is penicillin derivatives of heteroylcarboxylic acids (as a rule an isoxazol) in the third position of which is present a substituted or nonsubstituted phenyl radical (oxacillin, cloxacilhn, dicloxaciUin), which plays the role of the radical in the acyl side group. These penicillins (oxacilhn, cloxacilhn, dicloxacilhn), which are resistant to penicillinase, are active with respect to peniciUin-G-resistant staphylococci. Their antimicrobial spectrum is restricted to Gram-positive microorganisms. 

When (40) is irradiated by Hg lamp at room temperature in the presence of pentamethyl-cyclopentadienyl dicarbonyl cobalt(III), Co(III) dithiolato complexes (45) and (46) are formed implying involvement of benzonitrile sulfide as an intermediate <92CL243). Thermolysis of (40) (and its phenyl ring substituted derivatives (40a)) at 110-140 °C in aromatic solvents results in formation of another heterocyclic mesoionic structure (47) and appears to proceed as a radical process (Scheme 2) (91TL4023). The reaction is inhibited by radical scavengers. 

To confirm the structures of the products formed in the reaction between thienothiophenes 1 and 2 and phenyl radicals, the corresponding 2-phenyl- and 3-phenyl-substituted thienothiophenes 1 and 2 were synthesized by independent methods (see Section II,B). In addition, 2-phenyl-substituted thienothiophenes 1 and 2 were prepared by photolysis of the corresponding 2-iodo compounds, under conditions previously used with the iodothiophenes [Eqs. (86), (87)]. 

Free radical substitution of pyridines usually occurs principally at position 2 (Table 25), which is in agreement with theoretical calculations (69CCC1110). 2-Substitution is more favored in methylation than in phenylation of pyridine. This suggests that the methyl has more nucleophilic character than the phenyl radical. Furthermore, methylation of pyridine in acidic solution gives 13-fold excess of 2- over 4-substitution, although the overall yield is low. Alkyl and aryl radicals have been generated from diverse sources (Table 25). 

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