Fused 2,3,4,6-tetrasubstituted pyridines

Tri-substituted pyridine derivatives 201 were prepared by Katritzky et al. using a-benzotriazolyl ketones 199 and a,P-unsaturated ketones 200 in the presence of ammonitun acetate in refluxing acetic acid in good yields.Fused 2,3,4,6-tetrasubstituted pyridines 203 were also formed from the appropriate fused bicyclic ketone substrates 202. ... 

In 1999, Katritzky reported a novel [3+2+1] synthesis of 2,4,6-trisubstituted pyridine derivatives that used the Michael addition of a-benzotriazolyl ketones to a,P-unsaturated carbonyl compounds. This reaction resembles the Krohnke pyridine synthesis and is an extension of Katritzky s earlier studies with benzotriazolyl derivatives that provided access to pyridones, 2-thiopyridones, 5-alkyl-2,4-diphenylpyridines and 2-aminopyridines. This approach is attractive as both components are readily synthesized or commercially available. The availability of these starting materials allows for an efficient access to structurally diverse 2,4,6-triaryl pyridines when combined with ammonium acetate in acetic acid at reflux. In addition, it is possible to access fused 2,3,4,6-tetrasubstituted pyridines from the requisite fused bicyclic ketone starting material. The preparation of the pyridine ring via benzotriazole methodology has resulted in improved yields for many compounds and the opportunity to synthesize molecules with a substitution pattern that would be difficult to prepare by other methods. 

Fused 2,3,4,6-tetrasubstituted pyridines 7, 9 and 10 can be prepared by two complimentary procedures from fused bicyclic ketones. In the first synthetic approach it is the a,P-unsaturated ketone 6 that is part of the fused ring system. 

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