And cyclizations on reaction of azines with

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... 

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... 

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). 

The sequence for the synthesis of l,3,6-triazacycl[3,3,3]azines (58) is based on the reaction of 2,6-diaminopyridine with ethoxymethylene-malononitrile or ethyl ethoxymethylenecyanoacetate, leading to compounds 56. These on acylation gave 57, which after cyclodehydration yielded the desired cyclazines (58). Small amounts of the unsubstituted parent triazacyclazine (58a) were observed when the cyclization of 57 was carried out in a refluxing mixture of biphenyl and diphenyl ether. Decyanation of 4-cyano-2-methyl-l,3,6-triazacycl[3,3,3]azine (58f) with polyphosphoric acid at 200° yields 2-methyl-l,3,6-triazacycl-[3,3,3]azine (58b).18-80 The synthesis of 58d was carried out by a closely related route.74... 

Methyl groups vicinal to cyano substituents in azines readily condense with dimethylformamide dimethylacetal (DMFDMA) to yield dimethyl-aminoethenyl intermediates, which cyclize to give condensed pyridines in both acid and alkaline media. For example, reaction of the cyanopicolines (18, 19) with DMFDMA gives the enamines (20, 21), which are readily converted into the pyridopyridines (22, 23) on heating with HBr-AcOH (78JOC4878), Scheme 6. 

In addition, silver-catalyzed asymmetric aza-Diels-Alder reactions provide a useful route to optically active nitrogen-heterocyclic compounds such as piperidines or pyrid-azines. Substituted dihydrobenzofurans can also be enantioselectively prepared through silver-promoted allylation of aldehydes. Other types of silver-mediated cyclizations can also be used in the synthesis of tetrahydrofnrans, tetrahydropyrans, 1,2-dioxetanes, 1,2-dioxolanes, medium-sized lactones, dihydroisoqninolines, and so on. Silver salts can also be used as cocatalysts with other transition metals. Unique activity was observed for these silver-based systems in several cases. Conseqnently, the use of silver can enrich several available heterocyclization methods, and fnrther developments in the application of chiral silver complexes will hopefnlly appear in the near future. 

As mentioned previously, the cyclization of phenethyl ketone oximes with [Bu4N]Re04 and CF3SO3H and the cyclic imine formation from 0-sulfonyl oximes both proceed by intramolecular S 2-type reaction on the nitrogen atom of the oximes (Scheme 33). ° In contrast, both of the E- and Z-isomers cyclized smoothly and only 8-hydroxyquinoline was obtained regioselectively without forming 6-hydroxy derivatives. These phenomena are not consistent with a nucleophilic substitution reaction, and the cyclization of 0-2,4-dinitrophenyloxime 80a seemed to proceed by another reaction pathway (Scheme 37). To check isomerization of the 0-2,4-dini-trophenyloxime 84, the Z-isomer was treated with NaH and m-cresol. The isomerization of (Z)-84 hardly occurred, but 4-phenylbutan-2-one azine (85) and 4-phenyl-2-butanone (86) were obtained in 27 and 11%... 

---