Reactivity of Heterocycles

Electrophilic Attack on Carbon 3.02.2.4.1 Relative reactivities of heterocycles... 

The effect of substituents on the reactivity of heterocyclic nuclei is broadly similar to that on benzene. Thus mem-directing groups such as methoxycarbonyl and nitro are deactivating. The effects of strongly activating groups such as amino and hydroxy are difficult to assess since simple amino compounds are unstable and hydroxy compounds exist in an alternative tautomeric form. Comparison of the rates of formylation and trifiuoroacetylation of the parent heterocycle and its 2-methyl derivative indicate the following order of sensitivity to substituent effects furan > tellurophene > selenophene = thiophene... 

The high reactivity of heterocyclic diazonium ions in azo coupling reactions is the reason why in some cases the primary diazotization products cannot be isolated. For example, diazotization of 2-methyl-5-aminotetrazole (2.14) directly yields the triazene 2.15, i. e., the N-coupling product, since the intermediate diazonium ion is reactive enough to give the N-coupling product with the parent amine even under strongly acidic conditions (Scheme 2-8 Butler and Scott, 1967). 

The reactivity of heterocyclic dienes is determined by the nature and number of heteroatoms and, in the case of heteroaromatic compounds, also by the aromatic character. Furans undergo Diels-Alder reactions with strong dienophiles and generally afford cxo-cycloadducts which are thermodynamically more stable than the kinetically favoured c z/o-adducts. 

The reactivity of heterocyclic compounds composed of three fused ring systems (6 6 6) has been classified below according to general types of reactions. 

Dr. Wojciech Szczepankiewicz was born in Wolbrom, Poland, in 1959. He received his M.Sc. in polymer chemistry from the Silesian University of Technology in Gliwice, Poland, in 1985 and his Ph.D. in 1994 under the supervision of Prof. Jerzy Suwiriski at the same university. In 2002-03, he spent a period at Hasselt University (Belgium) with Prof. Dirk Vanderzande s lighting polymer research group. His research area is focused on the synthesis and reactivity of heterocyclic compounds in the azole and azine series. 

The reactivity of heterocyclic systems with carbenes, generated under phase-transfer catalytic conditions, has been reviewed for the period up to 1983 [1]. Most unsaturated non-heteroaromatic systems react with carbenes in the manner expected of alkenes, amines, amides, ketones, etc. (see Sections 7.3,7.5 and 7.6). 

Nobuhiro Sato was born in Niigata, Japan, in 1945. He received his B.Sc. degree from Yokohama City University in 1968 and his Ph.D. degree from Tokyo Metropolitan University in 1981. After a postdoctoral position with E. C. Taylor at Princeton University, he returned to japan, where he is now professor of chemistry at Yokohama City University. His research interests include synthesis and reactivity of heterocyclic compounds, particularly pyrazines and pteridines, as optically functional materials or bioactive products. 

The reactivity of heterocyclic rings is modified but not radically changed by benzo- or hetero-ring fusion. We therefore refer readers to the appropriate sections dealing with the analogous monocyclic rings ... 

The successful application of heterocyclic compounds in these and many other ways, and their utility in applied chemistry and in more fundamental and theoretical studies, stems from their very complexity this ensures a virtually limitless series of structurally novel compounds with a wide range of physical, chemical, and biological properties, spanning a broad spectrum of reactivity and stability. Another consequence of the varied chemical reactivity of heterocycles, including the possible destruction of the heterocyclic ring, is their increasing use in the synthesis of specifically functionalized non-heterocyclic structures. 

Research in the Department of Chemistry of the School of Pharmacy of the University of Bari Nucleophilic Reactivity of Aromatic Derivatives, and Synthesis and Reactivity of Heterocyclic Derivatives P. E. Todesco, Corsi Semin. Chim., 1968, 50-53. Nucleophilic Heteroaromatic Substitution G. Illuminati, Adv. Heterocyclic Chem., 1964, 3, 285-371. 

Two chapters deal with the increasing influence in heterocyclic chemistry of unusual heteroatoms. Igor D. Sadekov and Vladimir I. Minkin of Rostov University (Russia) survey the chemistry of tellurium-containing heterocycles with two heteroatoms, while Allan Blackman of the University of Otago (New Zealand) summarizes the influence of metals on the reactivity of heterocyclic ligands in his chapter, Reactions of Coordinated Ligands. ... 

The reactivity of heterocyclic compounds towards e-q can generally be deduced from the chemical behaviour of the aliphatic and aromatic systems discussed in the previous Sections. Thus one finds, for instance, that pyrrolidine (1) (tetraethyleneimine) (Szutkaetai., 1965) and proline... 

In this review we have gathered the important work on quantitative and mechanistic aspects of electrophilic aromatic reactivity of heterocycles. We have concentrated in particular on acid-catalyzed hydrogen exchange, nitration, and gas-phase elimination, these being the major efforts of our own research groups. However all other electrophilic substitution reactions are covered for completeness. 

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