Retrosynthetic Consideration of Heterocyclic Structures

In this chapter, the retrosynthetic analysis and proposals for the synthesis of heterocyclic compounds with one to three heteroatoms in five- or six-membered heterocyclic rings are presented. Such heterocyclic rings are constituents of thousands of biologically active compounds. Compendia on the synthesis and structural properties of all classes of heterocyclic compounds are available [1 ]. Numerous syntheses of heterocycles and descriptions of their physico-chemical properties are presented in separate chapters of organic chemistry handbooks cited in the introduction chapter of this book. 

We consider the key building blocks with two heteroatoms as the results of contemporaneous disconnections of two C-heteroatom bonds in the heterocyclic ring. This retrosynthetic step corresponds to cyclization by contemporaneous formation of two C-heteroatom bonds, a usual step in the synthesis of heterocyclic compounds. Depending on 1,2-, 1,3- or 1,4 relation of hetereoatoms in the heterocyclic ring, the corresponding building blocks possess heteroatoms bound directly in the germinal or vicinal position (Fig. 7.1). 

Sunjid and V. Petrovid Perokovid, Organic Chemistry from Retrosynthesis 

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A simple retrosynthetic analysis reveals that the neonicotinoids consist of a chloromethyl-substituted heterocycle and in most cases a nitroguanidine part. For discovery research as for industrial synthesis, the accessibility to these budding blocks is of considerable importcmce. Prior to the emergence of neonicotinoids, heterocycles of this structural type had not drawn particular attention, what has clearly changed ever since. [143,144]... 

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