Heteroaromatic compounds fused heterocycles

Xanthate 446 undergoes cyclization in the presence of camphorsulfonic acid via a radical chain reaction initiated by a small amount of lauroyl peroxide to give pyrroloimidazoles 449 in 56% yield. The use of an acid and anhydrous medium inhibits nucleophilic attack of the basic heterocycles at the xanthate moiety and allows radical reactions to occur. Fused heteroaromatic compounds can also be prepared directly from benzimidazole carrying an N-alkenyl substituent and xanthates by a tandem radical addition/cyclization to provide, for example, pyrrolobenzimidazole 453 in 57% yield (Scheme 106) <2002OL4345>. 

Analysis of the data on the chemistry of isomeric thienopyrimidines published over the last 10-15 years shows that this class of heteroaromatic compounds, which are structural analogs of natural compounds of the purine class, attracts increasing interest of chemists and biochemists. In the first half of the 21st century, new approaches to the synthesis of derivatives of these fused heterocyclic systems will be, undoubtedly, extensively developed. These derivatives are not only of theoretical interest but also possess a broad spectrum of practical use, primarily, due to various biological activities. Of the approaches to their synthesis, multicomponent cascade heterocyclization, which allows one to construct various functionalized thienopyrimidines and their fused analogs in one technologically and ecologically safe step, holds the most promise. 

Heteroatoms in five-membered 7i-excessive heteroaromatic compounds are responsible for the chemical behaviour of the molecules as a whole. The heteroatoms not only give electrons to form an aromatic n-electron system but also determine the direction of the attack of electrophilic or nucleophilic agents. In fused 7i-excessive heterocycles containing two or more heteroatoms, the reactivity of compounds and their physical properties are substantially affected by both the mutual arrangement of the heteroatoms and the electronic effects associated with their nature. 

All o-hetero-substituted arylmetals and aryl electrophiles (1) as well as heteroaromatic compounds represented by 2 and 3 are /3-hetero-substituted aryl derivatives. In most cases, /3-heteroatoms merely exert some rate-enhancing or -retarding influences on the Pd-catalyzed cross-coupling process. In some cases, however, their presence offers additional synthetic opportunities of potential significance. Synthesis of arene-fused heterocyclic compounds is particularly noteworthy, as indicated by the results presented below. However, most of the known examples involve cross-coupling-heteropalladation tandem processes, which are also discussed in Sect. V.3. So, they are very briefly mentioned in this section. 

Synthesis of Substituted Heterocycles Cu-mediated intermolecular coupling reaction of zirconacycles with dihalogenated heteroaromatic compounds is applicable for the synthesis of fused aromatic heterocycles. Zirconacyclopentadi-ene reacted with 2-iodo-3-bromothiophene in the presence of 2 equiv of CuCl and DMPU at 50 °C to afford the corresponding benzothiophenes 71. When 2-chloro-3-iodopyridine and 4-chloro-3-iodopyridine were used, the corresponding substituted quinolines 72 and isoquinolines 73 were obtained in high yields, respectively (Scheme 11.28) [28],... 

Fused Heteroaromatic Compounds.— The halogen in 4-chloroquinoline is readily replaced by the enolate anions from isopropylidine alkylmalonates and acetic anhydride in the presence of the heterocycle acylation of the nitrogen provides the necessary activation of the system. Attempted overall methylation of 2-methylquinoline by MeSOCH2 and DMSO gives only a minute amount of the... 

The site of dihydroxylation in heterocycles depends on the nature of the heteroaromatic system (Scheme 9.31) usually, electron-rich heterocycles like thiophene are readily biooxidized but give conformationally labile products, vhich may undergo concomitant sulfoxidation [241]. Electron deficient systems are not accepted only pyridone derivatives give corresponding cis-diols [242]. Such a differentiated behavior is also observed for benzo-fused compounds biotransformation of benzo[b] thiophene gives dihydroxylation at the heterocyclic core as major product, while quinoline and other electron-poor systems are oxidized at the homoaromatic core, predominantly [243,244]. 

Halogenation of heterocycles five-membered rings, 57, 291 fused to other aromatic and heteroaromatic rings, 59, 245 six- and seven-membered rings, 58, 271 of heterocyclic compounds, 7, 1 Hammett equation, applications to... 

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