Eight-membered heterocycles, aromaticity

Most of the highly unsaturated monocyclic eight-membered heterocycles contain one or two nitrogen atoms and have been obtained by bond reorganization processes from strained bicyclic or polycyclic precursors. Although several of the less substituted compounds without stabilizing substituents are highly labile substances, 1,4-dihydro-1,4-diazocines qualify as dihetera[8]annulenes and display distinct aromatic properties. 

The planarity or non-planarity of aromatic or potentially aromatic eight-membered heterocycles has already been discussed in Section 5.19.4, and will therefore not be further elaborated upon in this section. 

An interesting ring contraction of the eight-membered heterocycle (168) furnished the spirocycle (169) in which the aromaticity is lost (equation 52). Unfortunately, the stereochemical integrity of the rearrangement product was not commented upon. Ylides are used for ring expansion reactions likewise. The cis and trans isomeric ylides (170) and (173) lead to the same rearrangement product (172 s 175) with a trans double bond (Scheme 22). This result can be rationalized on the assumption that in each of the transition states (171/174) the ester enolate is equatorial. 

Aromatic nucleophilic denitrocyclization reactions leading to annulated five-, six-, seven-, and eight-membered heterocycles 02AHC(83)189. 

The two most common routes to eight-membered heterocycles involve either intramolecular or [1 + 7] cyclizations. Intramolecular cyclizations are particularly useful for precursors having two components tethered ortho to each other on an aromatic ring, which on ring closure lead to 1,3,6-benzoheterocycles, as exemplified by Schemes 14, 16, 17 and Equation (6), and 1,4,5-benzohetero-cycles, as demonstrated in Schemes 13, 19, and 25. 

As the examples in Scheme 9 illustrate, treatment of a styrenyl ether, such as 35, with 5 mol%Ru catalyst la under an atmosphere of Ar (14 h) leads to the formation of 36 and 37 in 42% and 41% isolated yield, respectively. When the reaction is performed under an atmosphere of ethylene, 36 is obtained in 91 % yield. Furthermore, as exemplified by the conversion of 38a to 39a, electronic properties of the aromatic moieties exhibit little influence on the facility of the catalytic heterocycle synthesis. Eight-membered rings are appropriate substrates as well (Scheme 9 38b—>39b). 

As the representative data in Table 6.4 indicate, the Zr-catalyzed resolution technology may be applied to medium-ring heterocycles as well in certain instances (e. g. entries 1 and 2), the starting material can be recovered with outstanding enantiomeric purity. Comparison of the data shown in entries 1 and 3 of Table 6.4 indicates that the presence of an aromatic substituent can have an adverse influence on the outcome of the catalytic resolution. The fact that the eight-membered ring substrate in Table 6.4 (entry 4) is resolved more efficiently may imply that the origin of this unfavorable effect is more due to the... 

The products derived from guanidines show aromatic reactivity. They are strongly nucleophilic and may be brominated and methylated in the heterocyclic ring. Reaction occurs with dimethylacetylene dicarboxylate to form the eight-membered insertion product 85. However, this is possibly produced by a two-step process involving electrophilic substitution of the heteroring rather than direct Diels-Alder addition, and this proposal is supported by the simultaneous formation of the substitution product 86. 

Melting points, where available, are given throughout this section for the individual compounds. Recent data on conformations of the novel 1,4-diazocines are presented in the context of discussion on the theoretical aspects (Section 14.06.2) and experimental structural methods (Section 14.06.3.1). An excellent review on aromaticity in heterocyclic chemistry, where heteroaromaticity of known and potential monocyclic eight-membered 1,4-diheterocines is a part of discussion, is also recommended <2004CR2777>. 

The nonaromatic eight-membered rings absorb little in the accessible regions of the UV spectrum. Table 13 gives some data on reported spectra for heterocycles whose absorptions are due to either fused aromatic rings, aromatic substituents or carbonyl bonds. 

Chapter 2 by Laszlo Nyulaszi and Zoltan Benko deals with the chemistry and physical organic chemistry of aromatic phosphorus heterocycles and is divided into four subchapters dealing with three-, four-, five-, and six-membered rings, in which there may be more than one phosphorus atom. The chapter begins with a clear presentation of the electronic structure that phosphorus may achieve in molecules with CP bonds. For cyclopentadiene and phosphole eight aromaticity indices are collected. Almost all of them indicate that phosphole is more aromatic than cyclopentadiene. It is also shown that even small structural effects (substituent, bonding modes) can have a substantial impact on the chemistry of the reported systems. 

With many treatises about heterocyclic compounds, and with the impressive series Comprehensive Heterocyclic Chemistry in three series (84CHEC1,96CHEC2-1,08CHEC3-1), it makes little sense to deal in detail with individual compounds. Rather, this review will discuss trends observed when m increases stepwise from m = 4 to m = 9. Actually, it will be seen that there are no heterocyclic sextet-aromatic systems with eight-or nine-membered rings, but we have included such structures because it may be worthwhile to explore whether their strain-free bicyclic isomers may evidence isomerization to planar monocyclic mesoionic systems. 

This chapter deals with heteromacrocycles rather than smaller-ring heterocycles. Traditionally, heterocycles are three- to eight- or nine-membered rings that contain one or more noncarbon heteroatoms. Many, if not most, of the known heterocycles are aromatic compounds in which the noncarbon atoms contribute electrons to meet Huckel rule requirements. The crown ether situation contrasts with that of traditional heterocycles. The bulk of crown ether compounds contain 12 or more members and are aliphatic rather than aromatic. Those heterocycles that have cation binding properties usually contribute one or at most two donors to a cation s primary solvation... 

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