Azines, reactions review

A large number of nucleophilic substitution reactions involving interconversions of pyridopyrimidines have been reported, the majority of which involve substituents in the pyrimidine ring. This subject has been reviewed previously in an earlier volume in this series which dealt with the theoretical aspects of nucleophilic re-activiti in azines, and so only a summary of the nucelophilic displacements of the substituent groups will be given here. In general, nucleophilic substitutions occur most readily at the 4-position of pyrido-... 

The third volume of this series covers three specific groups of compounds the carbolines (reviewed by R. A. Abramovitch and I. D. Spenser), the thiatriazoles (K. A. Jensen and C. Pedersen), and the pentazoles (I. Ugi). The remaining four chapters deal with topics of general chemical interest from the heterocyclic viewpoint the quaternization of heterocyclics (G. F. Duffin), carbene reactions (C. W. Rees and C. E. Smithen), applications of the Hammett equation (H. H. Jaffe and H. Lloyd Jones), and some aspects of the nucleophilic substitution of heterocyclic azines (G. Rluminati). 

The effects of the nucleophile on aromatic substitution which are pertinent to our main theme of relative reactivity of azine rings and of ring-positions are brought together here. The influence of a nucleophile on relative positional reactivity can arise from its characteristics alone or from its interaction with the ring or with ring-substituents. The effect of different nucleophiles on the rates of reaction of a single substrate has been discussed in terms of polarizability, basicity, alpha effect (lone-pair on the atom adjacent to the nucleophilic atom), and solvation in several reviews and papers. ... 

The criss-cross addition of azines of aromatic aldehydes with various electron-deficient olefins in which the double bond is terminal, for example, methyl acrylate, acrylonitrile, or in which allylic substituents do not sterically hinder the reaction, for example, maleic anhydride, is well known and was duly covered in CHEC-II(1996)<1996CHEC-II(8)747>, as well as in a review <1997ALD97>. Recently, the reaction has been used for the preparation of hyperbranched polymers <1998MI2655, 2002MAC712>. 

A process similar to that of Scheme 23, but involving 3-alkynyl derivatives of 76, viz. 78, leads to the isomeric series of pyrrolopyrimidopyridazines represented by 79 (Scheme 25) <2003RCB441>, and imidazopyrimidopyrid-azines such as 80 and 81 are similarly accessible via 3-(alkylamino) derivatives of 76 <2003T7669> (Equations 18 and 19). A review of the range and scope of these reactions is available <2005JHC375>. 

Addition and cyclization reactions of imines, catalysed by IS r0 ns led acids, have been reviewed, including examples in water solvent and enantioselective cases.65 Another review examines stereoselective nucleophilic additions to the C=N bond of aromatic azines (60 references).66 (g)... 

Hantzch synthesis is a well-known pathway to dihydro derivatives of azines. In some of the variations of this synthesis, the electrophilic reagents can be unsaturated ketones (Scheme 3.1, reactions a and b). Hantzch syntheses, including reaction b in Scheme 3.1 in which enamines are formed in situ from ammonia and the corresponding carbonyls, are not a topic of this book. However, synthetic applications of such condensations were described in detail in some reviews [1,2]. 

The longest chapter of this volume, authored by Roger Gallo and Christian Roussel (France) and Ulf Berg (Sweden), gives a comprehensive account of the quantitative treatment of steric effects in heteroaromatic compounds—a subject that has been advanced significantly by these authors. Finally, V. N. Charushin and O. N. Chupakhin (USSR) and H. C. van der Plas (The Netherlands) review reactions of azines with bifunctional nucleophiles. 

Abstract The chapter reviews the classic Reissert reaction, the keystone of a broad family of multicomponent reactions involving azines, electrophilic reagents and nucleophiles to yield A,a-disubstituted dihydroazine adducts. The first sections deal with the standard nucleophilic attack upon activated azines, including asymmetric transformations. Section 5 focuses on the generation of dipolar intermediates by azine activation, and on their subsequent transformation chiefly in cycloadditions. Lastly, Sect. 6 is primarily devoted to a special branch of this chemistry involving isocyanides. It also covers the reactivity of dihydroazines and reviews the mechanistic proposals for related reactions. 

Selective cathodic reduction of pyridines is a process of great industrial significanee [171]. As an example, dimethyl pyridinedicarboxylates undergo a highly selective electroreduction in methanol by use of a divided cell. The product obtained depends on the position of the substituents. Thus, the 2,3- and 2,5-dicarboxylates give the 1,2-dihydropyridines whereas the 2,6-, 3,4- and 2,4-dicarboxylates the 1,4-dihydropyridines [172]. Many other ring reductions of azines (often with dimerization as a side-reaction, see Section 6.4.3) are discussed in electrochemistry texts and reviews [116]. Attempts have been made to rationalize the herbicidal properties of dipyridinium salts in terms of their cathodic behavior [173]. 

The thermal and photolytic decomposition of hydrazine and substituted hydrazines and azines provide a source of many nitrogen containing radicals . For this reason a considerable amount of thermochemical data is now available relating to the bond energies of the bonds involved in these reactions. Friswell and Gowen-lock" have recently reviewed the chemistry and thermochemistry of nitrogen containing radicals, and the salient features of their article will serve as an introduction to this section. 

For a review article on the reaction of nucleophiles with azines, see ref 544. 

The chemistry of 1,3,5-triazinols has been reviewed.10,14,18,21 Cyanuric acid (1,3,5-tri-azine-2,4,6-triol) where the oxo form of the oxo-enol tautomerism predominates, is a thermally very stable compound (up to 500 JC). Thus, the chemistry is mostly based on the cyclic imide portion and the replacement reactions of the imido hydrogen atoms (halogenation, alkylation). 

The Chichibabin reaction and other aminations of nitrogen heterocycles have been reviewed. Accounts of the introduction of an amino group into azines and nitroaromatic... 

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