Fused to a Second Heterocyclic Ring

Imidazole Fused to a Six-Membered Heterocycle 1. Purine Bases and Related Compounds 

Protecting the amino group at N-6 in the form of A -(N-methyl-2-pyrroli-dineylidene)adenine improves the N-9 selectivity, although the yield tends to be lower. [For an account of the work by Jahne and co-workers see (93MI2).] 

the Pd(0)-catalyzed allylation of 2-amino-6-chloropurine 241 with (-)-259 affords 260, which produces (-)-carbovir upon hydrolysis. A similar allylation of adenine 238 gives 261, which on further elaboration gives (-)-aristeromycin. More recently Berranger and Langlois prepared the 

Moreno-Maflas, M. Prat, J. Ribas, and A. Virgili, Tetrahedron Lett. 29, 581 (1988). 

Falck-Pedersen, T. Benneche, and K. Undheim, Acta Chem. Scand. 43, 251 (1989). 

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A sulfoxide alkylatioii formed the key step of a synthesis of the important vitamin biotin. Biotin contains a five-membered heterocyclic sulfide fused to a second five-membered ring, and the bicyclic skeleton was easy to make from a simple symmetrical ester. The vital step is a double S 2 reaction on primary carbon atoms. 

Volume 45 of Advances in Heterocyclic Chemistry contains five contributions, all of which break new ground for this series. In the first article, Fujita and Nagao describe the use of heterocycles for the induction of chirality. This contribution represents an example of the way in which our subject is making itself increasingly felt throughout the whole fleld of chemistry. The second article, by TiSler, covers heterocyclic quinones, including the many classes in which a heterocycle is fused to a 1,2- or 1,4-benzoquinone ring. 

The second chapter is by E. S. H. E) Ashry, N. Rashed, M. Taha, and E. Ramadan of Alexandria, Egypt. They contribute the first of a two-part essay on fused 1,2,4-triazines. The present chapter deals with triazines fused to heterocycles with three-, four-, and five-membered rings. In a subsequent volume of the series we will cover triazines condensed with six-membered and larger rings. 

For most simple phenols this equilibrium lies well to the side of the phenol, since only on that side is there aromaticity. For phenol itself, there is no evidence for the existence of the keto form. However, the keto form becomes important and may predominate (1) where certain groups, such as a second OH group or an N=0 group, are present (2) in systems of fused aromatic rings and (3) in heterocyclic systems. In many heterocyclic compounds in the liquid phase or in solution, the keto form is more stable, although in the vapor phase the positions of many of these equilibria are reversed. For example, in the equilibrium between 4-pyridone (118) and 4-hydroxypyridine (119), 118 is the only form detectable in ethanolic solution, while 119 predominates in the vapor phase. " In other heterocycles, the hydroxy-form predominates. 2-Hydroxypyridone (120) and pyridone-2-thiol (122) are in equilibrium with their tautomers, 121 and 123, respectively. In both cases, the most stable form is the hydroxy tautomer, 120 and 122. ... 

A fairly large number of different fused (5 5 5) systems of three five-membered heterocyclic rings are reported in Chapter 8.35 of the Comprehensive Heterocyclic Chemistry (second edition) <1996CHEC-II(8)933>. In order to understand the various properties systemically, it is important to have an unambiguous idea about the structural patterns of different representative members of this unique fused (5 5 5) system of three five-membered rings. 

Most benzo-fused heterocyclic systems are constructed from a substituted benzene by synthesis of the heterocyclic ring. Similarly most bicyclic heterocycles with heteroatoms in both rings commence with a monoheterocycle and build on the second heterocycle. However, substituent modification and, to a lesser extent, substituent introduction are also important, particularly in the later stages of a synthesis, and we now survey available methods for this. 

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