Reaction Mechanisms in Heterocyclic Chemistry

As with any potential energy surface calculation, it is important that a sufficient level of theory is used in order to get reliable information about reaction mechanisms in heterocyclic chemistry. Molecular mechanics has been used extensively to calculate the endpoints of these reactions and to afford information about thermodynamic control and relief of strain, but the technique is not suited to the general study of transition structures. Semiempirical approaches have found wide application but a cautious user would compare the results with higher-level calculations or experimental observations. Although often successful, at least one study has found limitations in the semiempirical methods for heterocycles containing N-N bonds. ... 

As is common in heterocyclic chemistry, many studies concern tautomeric equilibria. While quantum chemical calculations are straightforward for the question of the most stable isomer, experiments are sometimes very demanding. Therefore, quantum chemistry can easily provide answers that may require substantial experimental effort. Comparatively few studies concern the investigation of entire reaction paths. This is much more demanding than computing a limited number of tautomers, of course, but usually provides a very detailed picture of the reaction mechanism. In certain cases, it was only possible to judge the nature of a chemical reaction on the basis of quantum chemical calculations. 

KATRITZKY POZHARSKII Handbook of Heterocyclic Chemistry, 2nd Edition LEVY TANG The Chemistry of C-Glycosides LI GRIBBLE Palladium in Heterocyclic Chemistry McKILLOP Advanced Problems in Organic Reaction Mechanisms MATHEY Phosphorus-Carbon Heterocyclic Chemistry The Rise of a New Domain OBRECHT Solid Supported Combinatorial and Parallel Synthesis of Small-Molecular-Weight Compound Libraries... 

Nucleophilic substitutions are in many cases facile processes in heterocyclic chemistry. Also, in the area of the present chapter, many such routine transformations have been carried out. Such transformations are summarized in Table 6, where the structures of the starting compounds, products, the reagents, yields, and references are listed. These include reactions of halogen, methoxy, and methylsulfanyl derivatives with amines or alkoxides. One exceptional case (Table 6, entry 9) should be pointed out this exchange reaction, unlike the others in this table, proceeds via an elimination-addition mechanism. A few related transformations that follow more complicated pathways and therefore could not be classified unambiguously into this table, can be found in Table 7 in Section 11.17.5.6.5. 

Another variant of the Heck reaction which is important in heterocyclic chemistry utilizes five membered heterocycles as olefin equivalent (2.2.)7 It is not clear whether the process, coined as heteroaryl Heck reaction follows the Heck mechanism (i. e. carbopalladation of the aromatic ring followed by //-elimination) or goes via a different route (e.g. electrophilic substitution by the palladium complex or oxidative addition into the C-H bond). Irrespective of these mechanistic uncertainties the reaction is of great synthetic value and is frequently used in the preparation of complex policyclic structures. 

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