Fused-ring five-membered heterocycles

Fused-Ring Five-Membered Heterocycles Indoles and Purines... 

Heteroindenes fused with five-membered heterocyclic rings. 

Oxidative procedures have been utilized for the synthesis of both monocyclic five-membered heterocycles and their ring-fused analogs, although the ease of synthesis of the precursors for the latter ring closures results in wider application of this procedure. A variety of oxidizing agents have been used and the conversion of the benzylidene hydrazidines (221) into the 4-arylamino-l,2,4-triazole (222) was effected with mercury(II) oxide (77BCJ953). 

A versatile method for the synthesis of a variety of five-membered heterocycles and their ring-fused analogs involves the reaction of a neutral 47r-electron-3-atom system with a 27T-electron system, the dipolarophile, which is usually electron deficient in nature. Available evidence, e.g. retention of dipolarophile stereochemistry in the product and solvent polarity exerting only a moderate influence on the reaction, indicates that the cycloaddition proceeds via a concerted mechanism 63AG(E)565, 63AG(E)633, 68JOC2291) and may be represented in general terms by the expression in Scheme 8. 

Just as in the Diels-Alder reaction, 1,4-dipolar cycloadditions lead to six-membered rings. Their principal use in five-membered heterocycles is for ring annulations giving [5,6] ring-fused systems. 

Unusual heterocyclic systems can be obtained by photodimerizations and for five-membered heterocycles with two or more heteroatoms such dimerizations need be effected on their ring-fused derivatives. Cyclobutanes are usually obtained as in the photodimerization of the s-triazolo[4,3-a]pyridine (540) to the head-to-head dimer (541). These thermally labile photodimers were formed by dimerization of the 5,6-double bond in one molecule with the 7,8-double bond in another (77T1247). Irradiation of the bis( 1,2,4-triazolo[4,3-a]pyridyl)ethane (542) at 300 nm gave the CK0ifused cyclobutane dimer (543). At 254 nm the cage-like structure (544) was formed (77T1253). 

Five-Membered Heterocycles Fused to One Benzene Ring... 

Various ring systems in which the pentathiepin ring is fused to a five-membered heterocyclic ring have "been described. 

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. 

All compounds reported within the review period are indolizines or their hetero-substituted derivatives, fused through the a- or -edge to a five-membered heterocyclic ring. 

Pyrano- and thiopyranopyridines and their aza analogues fused to a five-membered heterocycle 12.17.3.1,5(i) Pyran or thiopyran as the outer ring... 

Examples of different types of tropones and tropolones fused to a five-membered heterocyclic ring are given in Scheme 1. Different fusion with respect to the heteroatom or group (Z) leads to... 

Cycloproparenes in which the benzene ring is fused to a five-membered heterocyclic moiety are accessible by the cycloaddition route from the appropriate dienes 188. Both the fiiran and thiophene derivatives 189 and 190 are isolable, but both are highly reactive. TTie difluoro derivative 191, prepared by an analogous route, has also been synthesized but decomposed rapidly in solution, while 192 was not isolable." ... 

There are several bicyclic compounds with five-membered heterocycles fused to pyridine rings, where metalation occurs in the smaller ring due to activation by the heteroatom. The ring-A lithiation of imidazopyridines and pyrimidines was discussed in Section II,E,6, but in addition, the a-lithio derivatives of thieno[2,3-6]pyridine 119 (74JHC355), thieno[3,2-... 

Nitrile imines have been added to 1,4-diazepines (246) (143,144), 1,2, 4-triazepines (247) (145), 1-benzazepines (248) (146), 1,4-benzodiazepines (249-251) (147-149), 1,5-benzodiazepines (252, 253) (X = NH) (143,150-153), 1,5-benzothiazepines (253) (X=S) (153). Interest in this area has been stimulated by the known pharmacological activity of many compounds with five-membered heterocyclic rings fused to a benzodiazepine skeleton. 

Chimichi et al. have reported the synthesis and spectroscopic data for all four thiazolopyridine isomers in order to examine how the differently substituted fused five-membered heterocycle influences the chemical and spectroscopic properties <1997MRG601>. The unambiguous assignment of the chemical shifts of these systems was reported and coupling constants showed that azole ring fusion on the pyridine system is responsible for a significant... 

The synthesis of fused 1,2,3-triazoles is nearly always achieved by treating 1,2-diamines attached to diazines with nitrous acid (e.g., [l,2,3]triazolo[4,5-f]pyridazine (Section 10.13.9.2.1(iii)) and [l,2,3]triazolo[4,5-rf pyrimidine (Section 10.13.9.2.1(iv)), <1996CHEC-II(7)489>). When a heterocyclic system containing a diazole fused onto 1,2,4-triazine is required, annulation of the five-membered heterocycle is nearly always the most facile route (e.g., imidazo[4,5-r ][l,2,4]triazine (Section 10.13.9.2.l(i)) and pyrazolo[4,3-r ][l,2,4]triazine (Section 10.13.9.2.1(ii))). In support of the latter, the synthesis of the fused six-membered ring of pyrazolo[3,4-r ][l,2,4]triazine from the pyrazo-ledione was reported as low yielding <1996CHEC-II(7)489>. 

This chapter reviews the systems where account is taken of the size of the central carbocyclic ring, the relative orientation of the fused five-membered heterocyclic rings, the types of heteroatoms, their number, and, in rings with more than one heteroatom, their relative situations. 

FIVE-MEMBERED HETEROCYCLES FUSED TO A BENZENE RING... 

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