Flank benzene ring

These compounds consist of two benzene rings flanking the heterocycle therefore, the heterocycle contains only two heteroatoms. Most of the work on these compounds has centered on theoretical studies of the electronic structures and aromatic properties of these heterocycles references are given in Table 6. 

According to space-filling scale models, the molecules of chlorocarbons with the alkyl substituent flanked by two o-chlorines, such as perchlorotoluene, perchloroethylbenzene, perchloro-p-xylene and perchlorobi-p-tolyl, are highly strained (pp. 273, 274). In order to partly relieve that strain, some bending of bonds in the benzene ring takes place strained benzenes of this type are frequently severely distorted. In many cases, this has been ascertained by X-ray structural measurements. 

Nafcillin (Table 38.3). Nafcillin has a fused benzene ring on one flank and an ethoxy moiety on the other of the side-chain amide linkage. Although slightly more acid stable than methicillin, it is virtually identical to it clinically. 

An efficient method for the generation of useful dilithiated aryl-alkyl sulfides has been developed. The selectivity of the Br/Li exchange depends on the acidity of the hydrogen atoms in the aliphatic position. For the hydrogen atoms in the benzylic position, the acidity is strongly influenced by the substituent in the benzene ring. The non-benzylic hydrogen atoms in the a position to sulfur are rather unreactive towards deprotonation with Bu i, unless they are flanked by two sulfur atoms. 

The frequently observed bioisosteric relation of benzene and thiophene applies to the clonidine series as well. Reaction of the thiophenyl thiourea (85-1), in which the amine group is flanked by substituents as in the prototype, with methyl iodide and a base gives the corresponding methyl thioether (85-2). Treatment of that intermediate with ethylene diamine leads to the formation of an imidazoline ring and the antihypertensive agent, tiamenidine (85-3) [90], shown as its imino tautomer. 

---