Cyclizations 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... 

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... 

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. 

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). 

The specific features of meta-cyclization of aza-aromatic compounds with bifunctional nucleophilic reagents were formulated by Strauss in a number of papers on the reactions of polynitro aromatics and their aza-analogues with enamines, CH-active acetamidines, and other 1,3-dinucleophiles (74ACR181). 

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... 

One of the most common synthetic approaches to the construction of heterocyclic compounds involves the reaction of /3-keto esters with bifunctional nucleophiles. Thus a variety of reactions of (1) with different bifunctional heteronucleophiles, including hydrazine, substituted aminotriazoles, 2-aminopyridines, o-phenylenediamines, and o-aminothiophenol, lead to polynuclear condensed thieno compounds (e.g. 2-8) of potential medicinal interest featuring the pyrazolone, pyrimidinone, benzodiazepine, and benzothiazepine nuclei. Cannabinoid analogs can be prepared through cyclization of the condensation products of (1) with bifunctional oxygenated nucleophiles such as substituted resorcinols. ... 

---