Heterocycles, electrophilic substitution

For monographs, see Taylor, R. Electrophilic Aromatic Substitution Wiley NY, 1990 Katritzky, A.R. Taylor, R. Electrophilic Substitution of Heterocycles Quantitative Aspects (Vol. 47 of Adv. Heterocycl. Chem.) Academic Press NY, 1990. For a review, see Taylor, R. in Bamford Tipper Comprehensive Chemical Kinetics, vol. 13 Elsevier NY, 1972, p. 1. 

Another very mild procedure involves reaction of the alcohol with the heterocyclic 2-chloro-3-ethylbenzoxazolium cation.28 The alcohol adds to the electrophilic heterocyclic ring, displacing chloride. The alkoxy group is thereby activated toward a nucleophilic substitution that forms a stable product, 3-ethylbenzoxazolinone. 

This awareness in a short time led to new homolytic aromatic substitutions, characterized by high selectivity and versatility. Further developments along these lines can be expected, especially as regards reactions of nucleophilic radicals with protonated heteroaromatic bases, owing to the intrinsic interest of these reactions and to the fact that classical direct ionic substitution (electrophilic and nucleophilic) has several limitations in this class of compound and does not always offer alternative synthetic solutions. Homolytic substitution in heterocyclic compounds can no longer be considered the Cinderella of substitution reactions. 

Pyrrole, furan and thiophene undergo electrophilic substitution reactions. However, the reactivity of this reaction varies significantly among these heterocycles. The ease of electrophilic substitution is usually furan > pyrrole > thiophene > benzene. Clearly, all three heterocycles are more reactive than benzene towards electrophilic substitution. Electrophilic substitution generally occurs at C-2, i.e. the position next to the hetero-atom. 

Electrophilic aromatic substitution Electrophilic aromatic substitution of indole occurs on the five-membered pyrrole ring, because it is more reactive towards such reaction than a benzene ring. As an electron-rich heterocycle, indole undergoes electrophilic aromatic substitution primarily at C-3, for example bromination of indole. 

Electrophilic substitution is much easier than in benzene. Thiophene reacts about as readily as mesitylene pyrrole and furan react as readily as phenol or even resorcinol. Electrophilic substitution of heterocycles has been reviewed (86HC(44/2)l), (90AHC(47)87), and the following conclusions were reached ... 

The final two chapters both deal with aspects of the electrophilic substitution of heterocycles. Derek T. Hurst of Kingston University (England) summarizes nitrations which occur in phenyl rings as substituents in heterocycles. Finally, we present the second of the three-part series by M. Ross Grimmett (also from the University of Otago) on the haloge-nation of heterocycles. This part deals with six-membered heterocycles. 

Katritzky, A. R, Taylor, R., Electrophilic Substitution of Heterocycles Quantitative Aspects, 47, 1. 

The heterocyclic literature is enormous, and a significant fraction deals with electrophilic substitution reactions of heteroaromatics. A great many authors have provided quantitative data, but the data are scattered through the literature, rarely reviewed comprehensively, and still less interpreted. Indeed, a proper interpretation is possible only by taking the wider view. This is what this book is intended to provide. It has been found possible not only to give interpretations of all of these quantitative data—in many cases for the first time—but to consider, additionally, much of the semiquantitative and qualitative work on the electrophilic substitution of heterocycles. 

Volume 47 of Advances in Heterocyclic Chemistry is, unlike most volumes, a monograph and deals with the quantitative aspects of electrophilic substitution of heterocycles. It is written by Roger Taylor of the University of Sussex, Brighton, England, and your editor with one chapter contributed by Ross Grimmett of the University of Otago in New Zealand. It is hoped that this survey of the whole area of electrophilic substitution of heterocycles, covering as it does semiqualitative as well as completely quantitative aspects, will be of considerable help to workers in the field. 

Katritzky AR, Taylor R (1990) Electrophilic substitution of heterocycles quantitative aspects. In Katritzky AR (ed) Advances in heterocyclic chemistry. Academic Press, San Diego... 

Electrophilic substitution of heterocycles, quantitative aspects 90AHC(47)1. 

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