Fused heterocyclic systems

Provided that no retained trivial name is applicable, fused heterocyclic systems are given Hantzsch-Widman names. Fusion of components follows the same pattern as established for corresponding hydrocarbons and an intricate series of seniority rules must be run through for selecting the parent component. Traditional abbreviated terms are retained for the following fusion components furo, imidazo, (iso)quino, pyrimido, thieno. 

This rule is sometimes disregarded by Chem. Abstr. and the Ring Index for oxygen-containing three-membered rings  

Correct 8aH-Fluoreno[ l,2-b]oxirene C.A. l,2-Epoxy-8aH-fluorene R. I. 8aH-Oxireno[ i]fluorene 

Related thia derivatives are named as epithio... compounds by both handbooks. 

If a central system is fused to two (or more) identical peripheral senior components, name construction occurs as shown below  

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For fused heterocyclic systems too, we can often make predictions based on the above principles, though many exceptions are known. Thus, indole is chiefly substituted in the pyrrole ring (at position 3) and reacts faster than benzene, while quinoline generally reacts in the benzene ring, at the 5 and 8 positions, and slower than benzene, though faster than pyridine. 

Survey of Fused Heterocyclic Systems (6 5 6) with Ring Junction Heteroatoms 976... 

Many versatile approaches to the construction of fused heterocyclic systems (6 5 6) with ring junction heteroatoms have been reported. More general reactions which can be used for synthesis of derivatives of several tricyclic systems, and transformations which have potential for use in the preparation of a series of substituted compounds, are discussed in this section. Formation of the five-membered ring is presented first because it is a conceptually simple approach. It should be noted, however, that the addition of a fused six-membered ring to a bicyclic component offers much more versatility in the construction of a (6 5 6) system. Each subsection below starts with intramolecular cyclization of an isolated intermediate product. Reactions which follow are one-pot intermolecular cyclizations. 

The tricyclic fused heterocyclic system 236 containing a phosphorus atom was constructed by the Diels-Alder reaction. Thus, diazaphospholopyridine 235 was treated with 2,3-dimethylbutadiene in the presence of sulfur or selenium to give the product 236 (Equation 27) <2002JOC9162, 2002T1573, 2005T10521>. 

Further development of fused heterocyclic systems (6 6 6) to August 2007 is shown in Table 4. 

Reaction of 518 with various bifunctional compounds such as a-halogeno acids or esters results in the isolation of fused heterocyclic systems such as 520 [87IJC(B)110]. The factors affecting cyclization are dependent on the cyclizing agent as well as the nature of the side chain present in the parent compound. 

In view of the nature of this edition as a whole, the content of this chapter is restricted to describing the chemistry of monocyclic 1,2,4-triazole systems. Readers are directed to the relevant chapters elsewhere in this edition for details of the chemistry of fused heterocyclic systems that contain a 1,2,4-triazole moiety examples of fused systems are only cited in this chapter where relevant. 

Several of the fused heterocyclic systems discussed in this chapter have useful biological activities and little has been reported concerning other applications, such as their use as additives for motor fuels or as starting materials for color photographic couplers and dyes. The most significant applications found in the literature are summarized here. 

The [5,5] (2Nl)-fused heterocyclic system contains four ring-carbon atoms, the fusion carbon atom and two and one carbon atom in the respective five-membered rings. 

Fused heterocyclic systems derived from 3-mercapto-l,2,4-triazole can be obtained by heterocyclization of 4-allyl-l,2,4-triazole-3-thione derivatives by treatment with halogens or mineral acids <1996T791>. Compounds 342 react with bromine yielding thiazolium halides 28 in good yield (Equation 64) <2000RJOC1033>. 

The (5,5) (2N2)-fused heterocyclic system contains three ring carbon atoms, one fusion carbon atom, and one additional nonfusion carbon atom in each five-membered ring. Only scattered H and 13C nuclear magnetic resonance (NMR) data are available for these systems. 

Most of the (5,5) (2N2)-fused heterocyclic systems are fully substituted aromatic systems and therefore they do not have any hydrogens attached to the ring. Very little is reported on C-unsubstituted compounds. Methine groups are generally part of a ring azomethine moiety and are either linked to a fusion atom C or N or to a nonfusion atom N or S (Table 1). 

One of the earliest uses for rhodium(II)-catalyzed dipoles was demonstrated in Davies furan synthesis [22]. Isomiinchnones were also shown to produce substituted furans [115]. Additional furan syntheses have been described using silylacetates [116], unsaturated esters [117], and fluoroalkyl diazo acetates [118]. The synthesis of furofuranones and indenofuranones 35 from a-diazo ketones having pendant alkynes has also been reported (Eq. 6) [119]. Other fused heterocyclic systems include furo[3,4-c]furans [120, 121] furo[2,3-b]furans [122] as well as thiobenzofurans [123], and benzoxazoles[124] have also been synthesized with this methodology. 

Electron-poor fused heterocyclic systems can activate a neighboring benzene ring for nucleophilic substitution. Fluoroquinolines of type 30 were shown to react efficiently with hydroxylamine (equation 20) . 

The direct lithiation of benzo fused heterocyclic systems in the benzo ring is often less easy than in the heterocyclic ring or even at a substituent phenyl group. Thus, while A7-phenyl indole undergoes lithiation at both the 2- and the 2 -positions, /3-lithiation at the 7-position does not occur. The first observation of lithiation at the 7-position of an indole derivative was seen with tricarbonyl(T7 -l-methyl-2-trimethylsilylindole)chromium(0) 26, even though the major site of reaction was at C-4 (Scheme 28)... 

The condensation reactions of diacylfurazans and furoxans also provide a convenient means of constructing fused heterocyclic systems incorporating the 1,2,5-oxadiazole unit. Representative examples include the conversion of diaroylfuroxans into furoxano[3,4-r/]pyradizines (61) using hydrazine <92JHC87>, and the formation of furazano[3,4-c]pyridines (62) with primary amines and DBU <79S687>. 

Extensive work has been carried out on the 1,7-electrocyclization of diene-conjugated nitrile ylides (324) leading to fused heterocyclic systems containing the azepine ring (325). Reactions of this type for all 1,3-dipoles have been reviewed (197,198). 

In CHEC-II(1996), Chapter 7.03 <1996CHEC-II(7)89> was devoted to 5-5 fused heterocyclic systems containing four heteroatoms arranged 1 3, with no heteroatoms at the bridgehead position, that is, heterocycles of general structure 1 and 2. 

The structural diversity associated with bicyclic 5-5 fused heterocyclic systems containing two heteroatoms in each ring has been noted previously in both CHEC(1984) <1984CHEC(6)1027> and CHEC-II(1996) <1996CHEC-11(7)115>. In recent years this diversity has also been reflected in the number of applications that have been found for these compounds which include organic metals, molecular clips and receptors and molecular magnets. These fields will be examined in due course through this chapter. 

This chapter describes 6,6-fused heterocyclic systems, general structures 1-8, with no heteroatoms occupying a bridgehead position. Both aromatic and nonaromatic derivatives will be discussed, with the emphasis on those structures which contain only N, O, and S as the heteroatoms. The chapter concentrates on work published since 1995 but any key references prior to this, including those from CHEC-II(1996) <1996CHEC-II(7)625>, are included. 

An alternate method for building the partly saturated fused heterocyclic system for ticlopidine (10-4) starts by formation of the mesylate (11-2) from cyanopyridone (11-1) by treatment with methanesulfonyl chloride. The reaction of that with butyl thioglycolate can be envisaged as involving, first, the addition of the thiol group to... 

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. 

Abstract This chapter is devoted to recent progress in the chemistry of the 5 5 fused heterocyclic systems. There are four possible modes of 5 5 fusions of the simple five-membered heterocycles leading to four structures containing one heteroatom in each ring. The heteroatoms may be the same or different and may be O, NH, S, Se, Te, P, As, or Sb. The fully conjugated hetero analogs of pentalene dianion have a central C-C bond and are isoelectronic with the 10-7t-electron pentalene dianion. The scope of the chapter is outlined with a survey of various structural types and nomenclature of the parent compounds and their derivatives. New synthetic procedures and synthetic applications of title compounds are presented. This review has concentrated on the new developments achieved from 1997 to September 2007. 

Sequential Suzuki-Miyaura cross-couplings and Cadogan cyclizations were developed under microwave dielectric heating conditions to access a variety of 2-substituted carbazoles and other fused heterocyclic systems (Scheme 13). The use of microwave irradiation not only minimized the proto-... 

The synthesis of proline-fused heterocyclic systems by 1,3-dipolar cycloaddition has been well-established in solution-phase synthesis (Scheme 14) [42]. It is usually performed as a one-pot, three-component reaction of a dipo-larophile with an in situ prepared azomethine ylide. Perfluoroalkanesulfonyl protected hydroxybenzaldehydes [43] or fluorous alcohol protected amino esters [44] have been developed as two different fluorous components for the synthesis of proline derivatives 11 and 12. 

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