Substitution and radicals

Figure 2. Competing cydization and radical substitution pathways in pyrolysis of sdica-immobilized diphenylmethane.

Pyridines undergo radical substitution reactions preferentially at the 2-position. Yields and regioselectivity are generally higher if the reaction is carried out in an acid medium. The presence of a strongly electron-donating substituent (OH, OR, NR2) on the pyridine ring can alter the reactivity pattern of electrophilic and radical substitution. 

Finally attention must be drawn to the fact that the orienting effect of the nitro group in nucleophile and radical reactions usually differs from that in electrophilic reactions, and instead of meta orientation, ortho or para orientation takes place. The corresponding observations are referred to in chapters dealing with nucleophile and radical substitutions of nitro compounds (pp. 204, 207 and 212 respectively). 

Regioselective nucleophilic, electrophilic, and radical substitution in pyridines, di-, tri-, and tetrazines 88AHC(44)199. 

However, in contrast to benzene, ferrocene is sensitive to oxidation, and the ferrocenium cation, FeCpj, a paramagnetic 17-electron species, is readily formed in the presence of various oxidants. The ferrocenium cation is reluctant to undergo electrophilic substitution, and therefore reactions such as halogenation and nitration, which are important routes to substituted benzene derivatives, cannot be used for the synthesis of substituted ferrocenes. Only electrophilic substitution under nonoxidizing conditions (e.g., Friedel-Crafts acylation, Mannich reaction, borylation, lithiation or mercuration), and radical substitution are available as an entry into the chemistry of substituted ferrocenes. 

Many rDA reactions are carried out at temperatures of 150 °C or more in solution phase and often at temperatures of 400-600 °C using the flash vapor pyrolysis (FVP) method individual conditions are referenced throughout the text. However, an accelerating effect by anionic, cationic and radical substitution on either the dienophile or at the termini of the diene fragments has been predicted by Carpenter. Experimentally, this prediction has been substantiated only for anionic substitution. In 1%7, Hart reported what is likely the first example of an oxyanion-accelerated rDA reaction. Both oxyanionic " and car-banionic - substituents accelerate the cycloreversion reaction such that they proceed rapidly at room temperature (for example, equation 3). In addition, acid-catalyzed rDA reactions have been reported in which protonation effectively makes the dienophile fragment of the adduct more electron deficient. - Grieco has utilized a room temperature retro aza DA reaction useful for the V-methylation of dipeptides and amino acid derivatives (equation 4). "... 

This chapter describes in general terms the types of reactivity found in the typical six- and five-membered aromatic heterocycles. We discuss electrophilic addition (to nitrogen) and electrophilic, nucleophilic and radical substitution chemistry. This chapter also has discussion of orf/to-quinodimethanes, in the heterocyclic context. Organometallic derivatives of heterocycles, and transition metal (especially palladium)-catalysed chemistry of heterocycles, are so important that we deal with these aspects separately, in Chapter 4. Emphasis on the typical chemistry of individual heterocyclic systems is to be found in the summary chapters (7, 10, 13, 15, 19 and 23), and a more detailed examination of typical heterocyclic reactivity and many more examples for particular heterocyclic systems are to be found in the chapters - Pyridines Reactions and Synthesis , etc. 

C-substitution of nitrogen heterocycles , Vorbriiggen, H. and Maas, M., Heterocycles, 1988, 27, 2659 (discusses electrophilic and radical substitutions, lithiations and the use of iV-oxides) Regioselective substitution in aromatic six-membered nitrogen heterocycles , Comins, D. L. and O Connor, S., Adv. Heterocycl. Chem., 1988, 44, 199 (discusses electrophilic, nucleophilic and radical substitution, and metallation). 

Position 2 of the ergoline skeleton is highly suitable for synthetic modification of EA by both electrophilic and radical substitution. Many modifications have been reviewed by Rutschmann and Stadler (1978) chlorination, bromination and iodination, nitration and reduction of nitro derivatives to amino derivatives and reaction with 2-methoxy-l, 3-dithiolane affording an intermediate which can be desulfurised to a 2-methyl derivative. Troxler and Hofmann (1959) described the oxidation of lysergic acid diethylamide (LSD) to 2-oxo-3-hydroxy-2, 3-dihydrolysergic acid diethylamide. 

Table 8.2. Data of the ab initio calculations [25] on activation barriers of hydrogen abstraction from Eq. (8.3) and radical substitution from Eq. (8.5)...

Another attempt to meet this shortcoming of the theory, and also to provide a unified approach to electrophilic, nucleophilic and radical substitution, is found in the idea of frontier electron densities . Instead of referring ease of electrophilic and nucleophilic substitutions to high and low total 7r-electron density, respectively, this approach refers the former to the 7r-electron density due to the electron in the highest molecular orbital in the ground state, and the latter to the density in the lowest unoccupied orbital. Radical... 

Pyridine presents a great contrast to pyrrole as regards its ability to undergo substitution. Electrophilic substitutions are less numerous, varied and important than with the pyrroles. On the other hand, nucleophilic substitutions are of great consequence, and radical substitutions are more widely and significantly represented. 

This value is appropriate for nitration in sulphuric acid, i.e. for circumstances in which the nitrogen atom is protonated. Comparison with values derived for the nitrogen atom from nucleophilic and radical substitution ae show that the heterocyclic component of the ring should make the greatest effect upon electrophilic substitution and the least upon radical substitution, as is the case. 

No change of geometric configuration takes place during electrophilic and radical substitution at an olefinic C-atom. F. e. s. A. N. Nesmeyanov, A. E. Borisov, and N. V. Novikova, Izvest. 1969, 1216 C. A. 54, 1272b. 

Some mechanisms of electrophilic and radical substitution reactions Electrophilic substitution reactions have been proposed to occur by a general reaction path in which the attacking electrophilic group interacts first with the iron atom [287]. 

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