Nine-membered heterocycles, aromaticity

Ab initio, semi-empirical, and molecular mechanics calculations have been used extensively in the study of nine-membered heterocycles. Theoretical studies of heteronines have centered on the question of their aromaticity, which was surveyed as a part of general heterocycles aromaticity study <2004CRV2777>. Another important aspect is the conformation of the nonconjugated compounds (see Section 14.10.4.3). Computational aspects of conformational behavior of saturated nine-membered rings and nine-membered rings containing one torsional constraint were the part of the review <1999MI(5)89>. 

Eor reviews of 76 (X = N) and other nine-membered rings containing four double bonds and a hetero atom (heteronins), see Anastassiou, A.G. Acc. Chem. Res., 1972,5, 281, Top. Nonbenzenoid Aromat. Chem., 1973,1,, Pure Appl. Chem., J975, 44, 691. For a review of heteroannulenes in general, Anastassiou, A. G. Kasmai, H.S. Adv. Heterocycl. Chem., 1978, 23, 55. 

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. 

Figure 2 Synthesis of thiohydantoin library. Nine amino acids (Gly, Ala, Val, Phe, Asp, Ser, Met, Trp, His), 18 aromatic aldehydes (9 subst. Ph, 2 subst. Py, 4 five-member heterocyclic, bicyclic), and 19 isothiocyanates (12 aromatic, 1 bicyclic, 3 aliphatic, 3 sat. cyclic).

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... 

Seven- to nine-membered diaza heterocycles 101 were readily prepared from both ahphatic and aromatic diamines using this methodology. The use of microwave irradiation has a beneficial effect on the yield as compared to conventional heating (Scheme 28). 

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