Membered Aromatic Rings

In systems of fused six-membered aromatic rings, the principal canonical forms are usually not all equivalent. Structure 36 has a central double bond and is thus... 

Membered Aromatic Rings a) Non-Fused Thiophene Compounds... 

Boron. Five-membered aromatic rings containing a boron atom and two X-type heteroatoms display six jr-electrons and are consequently aromatic. Such systems are 1,3,2-dioxaborole (78) and its benzo derivative (79, Scheme 40).126-129 5,6-Diamino-1,3-... 

Dewar185-187 reported the first six-membered aromatic rings containing boron, oxygen, and nitrogen heteroatoms, and later Gronowitz188 prepared similar systems annelated with thiophene. The chemical reactivity and NMR data indicate electronic delocalization. 

A Hungarian research group reported on the hypotensive activity of 3-(pyrazol-l-yl)pyridazines of type (72) in rats [253-256]. The activity of these compounds (in which both of the hydrazino nitrogen atoms are incorporated into a five-membered aromatic ring system) has been found to be mediated by inhibition of prostaglandin-catabolizing enzymes. 

When two amide groups in a six-membered aromatic ring are in opposition to each other, as in maleic hydrazide, the oxo structure [143] is not so highly stabilized and tautomerism is observed in which the 6-hydroxy-3-pyridazone form [144] predominates (Katritzky and Lagowski, 1963). The p/fj-value of this compound is... 

Walker, P. D., Maggiora, G. M., Johnson, M. A., Petke, J. D., and Mezey, P. G. (1995) Shape group-analysis of molecular similarity—Shape similarity of 6-membered aromatic ring-systems../. Chem. Inf. Comput. Sci. 35, 568-578. 

The three most common five-membered aromatic rings are furan, with an O atom pyrrole, with an N atom and thiophene, with an S atom. 

A(other -(C=o) + nitrogen atoms in six-membered aromatic ring... 

In six-membered aromatic rings the intensity of the ring-stretching mode near 1600 cm 1 is related to the square of the ctr° parameter for the substituent and/or ring atoms. Such intensity measurements on 4-substituted pyridine A-oxides confirm the ability of the A-oxide group to both donate and withdraw electrons according to the nature of the 4-substituent. 

There are a number of heteroatom six-membered aromatic rings which are analogous to benzene in that they can donate six electrons to a metal. These include phosphabenzene. borabenzene anion, bomzire. and arsabenzene shown in Fig. I5.42.uv... 

Borazarophenanthrene was the first representative of a new class of heteroaromatic compounds containing boron atoms in six-membered aromatic rings.4 These compounds are of a different order of stability from previously known types of organoboron compounds, being chemically similar to normal aromatics, and their discovery has opened up a new field of aromatic chemistry. The procedure indicated here has been used to prepare a large number of related aromatic systems. 

A six-membered aromatic ring containing sulfur or oxygen must carry a positive charge. Pyrilium (26) is just such an example. It is unattractive to electrophiles, but nucleophiles readily attack the 2-, 4-, and 6-positions. 

Calculated properties were restricted to ClogP <3, the number of rotatable bonds <5, the number of hydrogen bond acceptors (HBA) <4 and the number of hydrogen bond donors (HBD) between 1 and 3. The topological polar surface area (TPSA) was set to <70 A2. In addition, a special feature count excludes structures that are too functionalised (feature rich) or dull (absence of pharmacophoric interaction points). This feature count is the sum of HBA, HBD and the number of five-and six-membered aromatic rings and selection was restricted to fragments with a feature count in the range 4-7. 

When there are two different heteroatoms in a five-membered aromatic ring, questions of regio-selectivity often arise. The unsymmetrical thiazole 27 might be disconnected at the imine to give the unstable primary enamine 28 and then at the thiolester to give an acylating agent and the undoubtedly very unstable 30. Note that 30 must have SH and NH2 on the same side of the alkene for cyclisation to be possible. We want to find a better way. 

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