Heterocyclic Systems with 1,2-Heteroatoms

Peri-annelated heterocyclic systems 411 with the inverse heteroatom orientation are formed on heating anthraquinone-1 -carboxylic acid 410 in aqueous solution of hydroxylamine hydrochloride (64MI1). 

By analogy with peri-hydroxynaphthoyl compounds, 1-acylanthraqui-nones 414 are converted into pyridazinoanthrones 415 on heating with 

The same principle was applied to the synthesis of the pyridazinone derivatives 417 with a fluorine nucleus (63ZOB1974). One can use peri- 

On lengthy heating of peri-nitronaphthaldehyde azomethine 419 with triethylphosphite, l//-l-ethyl-3-phenylnaphtho[ fe]pyridazine 420 is 

The azulene-pyridazine derivative 423 has been obtained by attachment of a seven-membered carbocycle to cyclopentadieno[ /]pyridazine 422 (78H387). Other azuleno[ fe]pyridazine derivatives have been similarly obtained (78H387). As for other peri-annelated heterocycles with 

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Heterocyclic Systems with Heteroatoms of the Same Name... 

Heterocyclic systems have played an important role in this historical development. In addition to pyridine and thiophene mentioned earlier, a third heterocyclic system with one heteroatom played a crucial part protonation and methylation of 4//-pyrone were found by J. N. Collie and T. Tickle in 1899 to occur at the exocyclic oxygen atom and not at the oxygen heteroatom, giving a first hint for the jr-electron sextet theory based on the these arguments.36 Therefore, F. Arndt, who proposed in 1924 a mesomeric structure for 4//-pyrone, should also be considered among the pioneers who contributed to the theory of the aromatic sextet.37 These ideas were later refined by Linus Pauling, whose valence bond theory (and the electronegativity, resonance and hybridization concepts) led to results similar to Hiickel s molecular orbital theory.38... 

Some condensed 6-6 heterocyclic systems with three or more heteroatoms have been generated from AAs. Derivatives of the pyrido[2,3-d]- or pyr-ido[3,2-d]pyrimidine systems 113 and 114 were prepared from 3-(or 2-)ethoxycarbonyl-2-(or 3-)isothiocyanatopyridine and AAs (90JHC413, 90JHC643). 

The literature contains examples of virtually all heterocyclic systems with two heteroatoms of nitrogen, sulfur and oxygen. However, in some cases simple derivatives of the parent... 

In Section 11.2 peptides based on a variety of aromatic heterocycles are discussed.1 2-21 Some of them are natural products with bioactivities ranging from antibiotics to double stranded DNA intercalators. Heterocyclic systems with five or six atoms, characterized by a single or a combination of N, O, and S heteroatoms, are described. In selected cases reduced, nonaromatic rings are also covered. 

R., Tautomerism of Heterocycles Condensed Five-Six, Five-Five, and Six-Six Ring Systems with Heteroatoms in Both Rings, 77, 51. 

The analogous phosphorus heterocyclic systems that include selenium or tellurium are discussed in detail in Chapter 6.12, and the systems incorporating phosphorus and arsenic or antimony are covered in Chapter 6.14. In addition, numerous examples of five-membered heterocyclic systems with phosphorus and elements of group III (B, Al, Ga, In) and group IV (Si, Ge, Sn, Pb) are included in Chapters 6.16 and 6.17 of this volume. The systems with five heteroatoms in a five-membered ring (e.g., pentaphospholide anion and tetrazaphospholium cation) and the fused heterocyclic rings (see Volumes 9-11) are beyond the scope of this chapter and are not covered here. 

Our interest in this chapter is in silver-catalyzed cycloisomerization reactions. Therefore, we shall present different silver-catalyzed cycloisomerization reactions as a function of the nucleophilic and electrophilic moiety. Cycloisomerization reactions including the classical ene-yne cycloisomerization (with X = CHR, Scheme 5.1), and the related heterocyclization reactions with heteroatoms embedded in unsaturated systems (X = NR, O Scheme 5.1) belong to the same reaction family. In addition, the alkynyl part can be exchanged for an allene unit. Internal or external nucleophiles (Nu) can then stabilize, through cascade reactions, the positive charge created.24... 

Heterocyclic systems with one heteroatom. Condensed heteroaromatic cations are reactive in [2 + 4] cycloaddition reactions with inverse electron demand. For instance, 2-benzopyrylium salts 403 react with vinyl ethyl ether to afford naphthalene derivatives 405 in good yields via initial adducts 404 <1990KGS315>. Similar transformations (Bradsher reaction) are also known for isoquinolinium salts <1984CC761>. 

We undertook a quantum chemical study of the protonation of monocyclic and benzannulated five-membered heterocyclic systems with one heteroatom (03KGS38). The initial calculations, carried out by the semi-empirical CNDO/2 method (81ZOR1129), gave values for the differences in energy of the cations formed on protonation of the a- and yS-positions iAEa-p) that corresponded with the available experimental data on the sequence of change in positional selectivity furan > thiophene > pyrrole. However, the place of selenophene between thiophene and pyrrole in this series predicted by these calculations was contradicted by the experimental results obtained later (95JHC53). The results of calculations by the MNDO and PM3 methods also did not fit the experimental data, possibly linked with poor parametrization for selenium atom (97M12). 

Most practitioners of heterocyclic chemistry will concur with the statement by Newkome and Paudler that the chemistry of heterocyclic compounds encompasses most, if not all, of the general reactions of organic chemistry. The presence of heteroatoms merely endows the heterocyclic systems with some additional, theoretical predictable properties [1]. Thus we have here the whole body of organic chemistry, plus something peculiar to this (very large) class of compounds. 

Domino or cascade reactions provide valuable approaches, especially to various carbo- and heterocyclic systems with three, four, or even more annelated rings. The Heck reaction has successfully been employed in various inter-inter-, intra-inter-, inter-intra-, as well as all-intramolecular reaction cascades, hi this section, the termination of these processes by alkenes, arenes, and related ir-bond systems such as alkynes and allenes will be described. A cascade Heck reaction is considered to consist of an oxidative addition of a heteroatom-carbon bond to palladium (starter), carbopalladation of a nonaromatic carbon-carbon double or triple bond without immediate dehydropalladation (relay), one, two, or more fimher car-bopalladation(s) of a carbon-carbon double or triple bond, and eventually ensuing dehydropalladation. Crucial for a cascade reaction of this kind to occur is the blockage or retardation of a dehydropalladation at one of the intermediate stages by using 1,1-disubsti-tuted alkenes and appropriately substimted cycloalkenes, bicycloalkenes, or alkynes as relays since they give kinetically stable alkyl- or alkenylpalladium intermediates, respectively. 

In contrast to the above, the reaction of a heterocyclic thione with an a-halogenoketone (Scheme 3) has been widely exploited as a route to [5,6] ring-fused systems with a heteroatom at a ring fusion point. 

Numerous examples of the ring closure of a binucleophilic system with a 1,1 -bielectrophile leading to five-membered heterocycles with three or more heteroatoms have been described, the popularity of this route no doubt reflecting the comparative ease with which the penultimate product may be obtained. 

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). 

Although widely applied in functional group modification in a variety of heterocyclic systems, phosphorus ylides have only been employed sparingly in heterocyclic ring construction with two or more heteroatoms in the nucleus. Their potential is shown in the applications illustrated below. 

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