Cyclizations azines with bifunctional nucleophiles

Charushin, V. N., Chupakhin, O. N., van der Plas, H. C., Reactions of Azines with Bifunctional Nucleophiles Cyclizations and Ring Transformations, 43, 301. 

Reactions of Azines with Bifunctional Nucleophiles Cyclizations and Ring Transformations... 

These examples seem to indicate that the interaction of azines with bifunctional nucleophiles can result in the formation of cyclization products only if we deal with an azine in which the reactivity of the leaving groups is enhanced by aza-activation or by the presence of electron acceptors. It has been found indeed that diazines, triazines, etc., are more inclined to cyclization than are pyridines. 

The meta-bridging cyclizations of azines with bifunctional nucleophiles usually occur in two steps and differ substantially in that respect from the 1,3-dipolar addition reactions performed on 3-hydroxypyridinium salts, which also result in meta-bridged adducts (Scheme 55) (76JCS(P1)2285). 

Reissert compounds, 9, I 24, 187 Ring closure of ortlio-substituted t-anilines, heterocycles by, 14, 211 Ring-opening of flve-membered heteroaromatic anions, 41, 41 Ring synthesis of heteroaromatic nitro compounds, 25, 113 Ring transformations and cyclizations on reaction of azines with bifunctional nucleophiles, 43, 301 of five-membered heterocycles, 56, 49... 

There are several examples known of participation of azines in cyclizations with 1,5- and 1,6-dinucleophiles (77T981 84H743, 84H1017). Reaction of the thia analogue of isoalloxazine 11 with bifunctional nucleophiles has been... 

Reactions of pteridines, quinoxalinium, and alloxazinium salts with bifunctional nucleophilic reagents as exhibited above in Schemes 7, 9, and 10 show examples of ortho-cyclizations. They proceed mainly in the series of 1,4-diazines, although examples of the participation of other azine derivatives in ortho-cyclizations with dinucleophiles are also known (85KGS1011). 

Betainic alkaloids and nucleobases, 85, 67 Bicyclic 6/5 ring-fused systems with bridgehead nitrogen, 49, 193 Bifunctional nucleophiles cyclizations and ring transformations on reaction of azines with, 43, 301... 

Bifunctional nucleophilic reagents, such as ketones, enamines, / -diketones and their derivatives, amidines, thioureas, thioamides, dithiocar-bamates, and others, are very often employed in cyclizations with azine derivatives, resulting in the formation of annelated five-membered cycles (84UK1648 85KGS1011). The structure of all these 1,3-dinucleophiles feature a double bond conjugated with an anionic center or with a heteroatom bearing the lone pair of electrons (Scheme 5). 

Another approach to the synthesis of condensed azine derivatives (84UK1648 85KGS1011) is based on the ability of a number of azine derivatives to undergo diaddition reactions with nucleophiles. When bifunctional nucleophilic reagents are used, these additions result in the formation of cyclization products. In all these reactions the tetrahydro analogues of the fully unsaturated heterocyclic systems are obtained. 

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