Heterocyclic compounds electrophilic aromatic

The numerical value of hardness obtained by MNDO-level calculations correlates with the stability of aromatic compounds. The correlation can be extended to a wider range of compounds, including heterocyclic compounds, when hardness is determined experimentally on the basis of molar reffactivity. The relatively large HOMO-LUMO gap also indicates the absence of relatively high-energy, reactive electrons, in agreement with the reduced reactivity of aromatic compounds toward electrophilic reagents. 

Udenfriend et al. observed that aromatic compounds are hydroxyl-ated by a system consisting of ferrous ion, EDTA, ascorbic acid, and oxygend Aromatic and heteroaroinatic compounds are hydroxylated at the positions which are normally most reactive in electrophilic substitutions. For example, acetanilide gives rise exclusively to the o-and p-hydroxy isomers whereas quinoline gives the 3-hydroxy prod-uct. - The products of the reaction of this system w ith heterocyclic compounds are shown in Table XIII. 

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. 

A-Amine oxides can be reduced (deoxygenated) to tertiary amines. Such a reaction is very desirable, especially in aromatic nitrogen-containing heterocycles where conversion to amine oxides makes possible electrophilic substitution of the aromatic rings in different positions than it occurs in the parent heterocyclic compounds. The reduction is very easy and is accomplished by catalytic hydrogenation over palladium [736, 737], by borane [738], by iron in... 

In addition to benzene and naphthalene derivatives, heteroaromatic compounds such as ferrocene[232, furan, thiophene, seienophene[233,234], and cyclobutadiene iron carbonyl complex[235] react with alkenes to give vinyl heterocycles. The ease of the reaction of styrene with substituted benzenes to give stilbene derivatives 260 increases in the order benzene < naphthalene < ferrocene < furan. The effect of substituents in this reaction is similar to that in the electrophilic aromatic substitution reactions[236]. 

The great variety of available structural types causes heterocyclic aromatic compounds to range from exceedingly reactive to practically inert toward electrophilic aromatic substitution. 

Neta P (1972) Reactions of hydrogen atoms in aqueous solutions. Chem Rev 72 533-543 Neta P, Schuler RH (1972) Rate constants for reaction of hydrogen atoms with aromatic and heterocyclic compounds. The electrophilic nature of hydrogen atoms. J Am Chem Soc 95 1056-1059 Neta P, Fessenden RW, Schuler RH (1971) An electron spin resonance study of the rate constants for reaction of hydroqen atoms with organic compounds in aqueous solutions. J Phys Chem 75 1654-1666... 

A useful property of hyper valent iodine reagents is their ability to react first as an electrophile and then to be transformed into an excellent leaving group. This particular aspect has been used in different rearrangements for the construction of highly functionalized molecules. Various iodine(III) reagents have been employed in Hofmann-type rearrangements [136-139]. The presence of a nucleophile in the ortho position of aromatic amides of type 72 can lead to direct cyclizations and to the formation of heterocyclic compounds 73 as shown in Scheme 33 [140]. 

Wide synthetic possibilities for modification of coordinated ligands are opened up by the classic reactions of electrophilic and nucleophilic substitution in complexes of aliphatic, aromatic, and heterocyclic compounds [314,359,418 422]. For example, the transformations (3.196) were known long ago [419] ... 

Both acid and base catalysis have been used extensively to catalyze exchange in aromatic, and to a lesser extent, heterocyclic molecules. In acid exchange, the most widely used catalysts are sulfuric acid,122,129, 131 phosphoric acid,132 trifluoroacetic acid5133 perchloric acid,134 aluminum chloride,135 and the phosphoric acid-boron trifluoride complex.132 These reactions constitute the simplest electrophilic substitution. The mechanism for such substitution in benzenoid compounds is now comparatively well understood 122 however, the problem of heteroaromatic electrophilic substitution is still being clarified and has led to renewed interest in acid-catalyzed exchange in heterocyclic compounds.122... 

Certain aromatic and heterocyclic compounds having reactive nuclear positions undergo direct amination. Thus a-nitronaphthalene on treatment with hydroxylamine in methanolic potassium hydroxide yields 4-nitrol-naphthylamine (60%)," following the rules of orientation for substitution by a nucleophilic reagent rather than an electrophilic reagent. 

Kawase, M., et al.. Electrophilic Aromatic Substitution with N-Methoxy-N-acylnitrenium Ions Generated from N-Chloro-N-methoxyamides Syntheses of Nitrogen Heterocyclic Compounds Bearing a N-Methoxy-amide Group, J. Org. Chem., 54 3394-3403 (1989). 

There is, for example, no end-of-text chapter entitled Heterocyclic Compounds. Rather, heteroatoms are defined in Chapter 1 and nonaromatic heterocyclic compounds introduced in Chapter 3 heterocyclic aromatic compounds are included in Chapter 11, and their electrophilic and nucleophilic aromatic substitution reactions described in Chapters 12 and 23, respectively. Heterocyclic compounds appear in numerous ways throughout the text and the biological role of two classes of them—the purines and pyrimidines—features prominently in the discussion of nucleic acids in Chapter 27. 

The formation of the C = O radical can be explained by considering the fact that pyrrole is a heterocyclic compound, considered as aromatic because of the delocalisation of the jr-electrons wich stabilize the ring. These delocalized 7r-electrons are very reactive and they can promote aromatic electrophilic substitution, wich produces to nitration reactions. Usually aromatic nitriles are obtained by means of nitrogen salts (N24), wich comes from aromatic amines, pyrrole in our case. The final step of the overall reaction is the production of the radical carbonyl. However, the polymerization of conductive PPy it must be avoided. Plays de role of TFB as electrolyte acts as activator of the reaction. 

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