Heterocyclic ring systems

Some common monocyclic hetero systems have trivial names, for example, pyridine, furan (see Table 4.1). 

Hantzsch-Widman names are used for one-ring heterocyclic systems that do not have trivial names. The names are applied to monocyclic compounds containing one or more heteroatoms in three- to ten-membered rings. The names are derived by combining the appropriate prefix or prefixes for the heteroatoms with a stem denoting the size of the ring (see below). The state of hydrogenation is indicated either in the stem or by the prefixes dihydro-, tetrahydro-, etc. 

The prefixes are the normal replacement prefixes (see Replacement Nomenclature, page 50), although elision of the final a often occurs. The prefixes are cited in the following order fluora-, chlora-, broma-, ioda-, oxa-, thia-, selena-, tellura-, aza-, phospha-, bora-, and mercura-. Chemical Abstracts does not use Hantzsch-Widman names for rings containing silicon. 

The stems for unsaturated rings imply the maximum possible number of noncumulative double bonds. Rings with more than ten manbers are named by replacanent nomenclature, e.g., azacycloundecane. 

Several modifications were later made in order to avoid confusion with other compounds for example, phosphorine was used instead of phosphine. The modified (extended) Hantzsch-Widman system (Pure Appl. Chem., 55,409,1983) uses the stems shown in Table 4.3. 

Iron and cobalt carbene complexes are capable of much more selective furan synthesis. Reactions of cobalt methoxycarbenes with internal alkynes give good to excellent yields of 2-methoxyfurans and have been applied to a synthesis of a natural product, bovolide [75 b]. Both terminal and internal alkynes are viable substrates in the preparation of 2-aminofurans from iron (dimethylamino)carbenes [78], although the nature of the rearrangement of the heteroatom-containing substituent is also as yet unclear [Eq. (33)]. The inclusion of elevated carbon monoxide pressure can divert this reaction to the production of pyrones [75c, 79]. 

Of the nitrogen heterocycles that have been observed as the product of Fischer carbene/alkyne reactions, pyrroles are the most readily obtained, with at least two efficient. 

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Transformations from Other Heterocyclic Ring Systems... 

All compounds of this heterocyclic ring system so far found in nature are derivatives of pterin (2) and lumazine (3) carrying different substituents in the 6- and/or 7-positions. The most common representatives of these series are listed in Tables 8 and 9. 

The two alkaloids which have been most completely investigated are quinine and cinchonine. The scission products of both fall into two classes, viz., derivatives of quinoline and derivatives of a second heterocyclic ring system, formerly referred to as the second half of the... 

Dewar and Turchi carried out similar rearrangements of secondary and tertiary alkyl and aryl oxazole-4-carboxamides (5a-e) to the corresponding secondary and tertiary 5-aminooxazoles (6a-e). For example, they realized yields > 90% when the amide nitrogen is part of a heterocyclic ring system. 

A number of intramolecular rearrangements of 1,2,3,4-tetrahydro-j8-carboline derivatives have been reported. Some of these lead into other naturally occurring heterocyclic ring systems and are therefore of particular interest. 

Finally, aromatic nucleophilic denitrocyclization reactions are reviewed for the first time by Stanislav Radi (Prague, Czech Republic). The nitro functionality is a good leaving group, especially for intramolecular reactions, and many such reactions lead to polycyclic heterocyclic ring systems. Frequently, these transformations are a method of choice for preparative purposes. 

Antidepressant activity is retained when the two carbon bridge in imipramine is replaced by a larger, more complex, function. Nucleophilic aromatic substitution on chloropyridine 31 by means of p-aminobenzophenone (32) gives the bicyclic intermediate 33. Reduction of the nitro group (34), followed by intramolecular Schiff base formation gives the required heterocyclic ring system 35. Alkylation of the anion from 35 with l-dimethylamino-3-chloropropane leads to tampramine 36 [8]. 

Heterocyclic amines—compounds in which the nitrogen atom occurs as part of a ring—are also common, and each different heterocyclic ring system has its own parent name. The heterocyclic nitrogen atom is always numbered as position 1. 

The first synthesis of this heterocyclic ring system, 224, was carried out (86S71) by the amination of aminopyrazole 222 with H2N0S03H fol-... 

The intramolecular Hiyama reaction is excellently suited for the construction of carbocyclic and heterocyclic ring systems of different size. In most examples, problems of induced diastereoselectivity are involved (Sections 1.3.3.3.9.2.2. and D.2.3.). In the total synthesis of the antitumor germacranolide ( )-costunolide from ( ,.E)-farnesol, the correctly substituted ( , )-cyclodecadiene moiety was constructed by an intramolecular Hiyama reaction22. 

The term benzodiazepine refers to a chemical structure, consisting of a heterocyclic ring system in which the two N atoms are mostly located in positions 1 and 4 (1,4-benzodiazepines), e.g., in diazepam (Fig. 1). 

Roseophilin (273), a deeply red-colored pentacyclic compound isolated from the culture broth of Streptomyces griseoviridis, is a novel antitumor antibiotic. Compound 273 possesses a topologically unique pentacyclic skeleton, consisting of a 13-membered macrocycle incorporated in an ansa-bridged azafulvene, which in turn is linked to a conjugated heterocyclic ring system. The absolute stereochemistry of roseophilin, as depicted in Fig. 9, was unknown until the first total synthesis published by Tius and Harrington in 2001 [125]. All syn-... 

While these reports are mainly concerned with an evaluation of the peculiar structure of the iminophosphenium cation, this species also reveals cycloaddition properties. The cation shows a [2-t-l] cycloaddition behaviour towards alkynes [50]. With iminophosphanes and alkylazides the cations react with the formation of four- and five-membered heterocyclic ring systems [51], as shown for example in Scheme 9. 

Two heterocyclic ring systems that have found some use in the formation of amides under mild conditions are lV-alkyl-5-arylisoxazolium salts (16A) and lV-acyloxy-2-alkoxydihydroquinolines (16B). 

Phenylthio)nitroalkenes are also excellent intermediates for the synthesis of other heterocyclic ring systems. For example, tetrahydropyran carboxylic acid derivatives are formed by the intramolecular addition of oxygen nucleophile to l-(phenylthio)nitroalkene predominantly as the m-isomer (9.1 1) (see Eq. 4.40). The reaction may proceed via the chair-like transition state with two pseudo-equatorial substituents.50... 

Although 1,3,2-diazaphospholenium cations are usually prepared from neutral NHPs or 1,3,2-diazaphospholes via Lewis-acid induced substituent abstraction or A-alkylation, respectively (cf. Sect. 3.1.2), the group of Cowley was the first to describe a direct conversion of a-diimines into cationic heterocycles by means of a reaction that can be described as capture of a P(I) cation by diazabutadiene via [4+1] cycloaddition [31] (Scheme 4). The P(I) moiety is either generated by reduction of phosphorus trihalides with tin dichloride in the presence of the diimine [31] or, even more simply, by spontaneous disproportionation of phosphorus triiodide in the presence of the diimine [32], The reaction is of particular value as it provides a straightforward access to annulated heterocyclic ring systems. Thus, the tricyclic structure of 11 is readily assembled by addition of a P(I) moiety to an acenaphthene-diimine [31], and the pyrido-annulated cationic NHP 12 is generated by action of appropriate... 

Lipophilicity and specific hydrophobic surface area were determined by using reversed-phase thin-layer chromatography for fused heterocyclic ring systems including five pyrido[2,iy][l,2,4]triazine derivatives <1998MI64>. 

The [l,2,3]triazolo[2,l- ]benzotriazole (74 2,3-benzo-l,3a,4,6a-tetraazapentalene) heterocyclic ring system is obtained by an electrophilic attack of singlet nitrene, generated by heating the corresponding nitrophenyl triazole 251 in trialkyl phosphite, on the triazole nitrogen (Equation 39) <1998JOC3352>. 

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