Disubstituted Ring Compounds

We have already mentioned that cis and trans diastereomers exist for dichlorocy-clopropanes (Chapter 4, pp. 173—176) and that the trans form is chiral (Fig. 5.32). 

When the two substituents on the ring are different, as in l-bromo-2-chloro-cyclopropane, two pairs of enantiomers are possible, and both the cis and trans forms of this molecule are chiral (Fig. 5.33). 

Stereochemical relationships become harder to see in cyclohexanes, where the molecules are not planar, but they don t really change. We will first take a look at 1,1-dialkylcyclohexanes and then at the somewhat more complicated 1,2-dialkylcyclohexanes. 

1-Isopropyl-l-methylcyclohexane is only slightly more complicated. There are two isomers, nearly equal in energy, neither of which is chiral (Rg. 5.35). 

FIGURE 5.35 Both isomers of 1-isopropyl-l-methylcyclohexane are achiral—the mirror images are superimposahle. 

---

Because the position of electrophilic attack on an aromatic ring is controlled by the dir ecting effects of substituents aheady present, the preparation of disubstituted aromatic compounds requires that careful thought be given to the order of introduction of the two groups. 

All preparations of this ring system involve the condensation of hydrazine and substituted hydrazines with functionally disubstituted pyridazines. The unsubstituted ring compound (6) is prepared by reducing diethyl pyridazine-4,5-dicarboxylate with LAH to give the dialdehyde (156). This intermediate product is not isolated but is reacted immediately with hydrazine to give the desired ring system (6) (67CC1006). 

Substituted aromatic compounds are named using the suffix -benzene. Thus, C6H5Br is bromobenzene, C6H5CH3 is methylbenzene (also called toluene), C6H5N02 is nitrobenzene, and so on. Disubstituted aromatic compounds are named using one of the prefixes ortho-, meta-, or para-. An ortho- or o-disubstituted benzene has its two substituents in a 1,2 relationship on the ring a meta- or m-disubstituted benzene has its two substituents in a 1,3 relationship and a para- or p-disubstituted benzene has its substituents in a 1,4 relationship. When the benzene ring itself is a substituent, the name phenyl (pronounced fen-nil) is used. 

The C-N bond cleavage of a benzo tetrahydroisoquinoline compound with lithium metal followed by aqueous quenching formed a naphthalene derivative Equation (1) <2000T8375>. An isoquinolinium ring system has been converted into a highly functionalized 1,2-disubstituted benzene compound. Ring opening of the quaternary salt was... 

The presence of a fluorine or a chlorine atom on the aromatic ring clearly leads to two different behaviors, giving two different products—aniline-1- or anilinium ion with formation of HX or X. Apparently, two different reaction coordinates are involved. In disubstituted aromatic compounds, depending on the nature of the substitutents, these two processes are competitive. 

With substituted benzene rings, an alternative way of identifying the positions of the substituents is to use the terms ortho, meta, and para. Ortho compounds are 1,2-disubstituted, meta compounds are 1,3-disubstituted, and para compounds are 1,4-disubstituted. Some examples should make this clear. 

Haworth reaction A reaction in which an aryl compound is treated with a cyclic anhydride, such as succinic anhydride, and the intermediate Friedel-Crafts product is reduced and then cyclised via an internal Friedel-Crafts reaction to give a 1,2-disubstituted aromatic compound with a carbonyl group in the new ring. The whole sequence is called the Haworth reaction. 

Reaction of ortho-disubstituted aromatic compounds 35 with sulfurating agents gives rise to l,2-dithiole-3-thiones where the dithiole nucleus is condensed with the aromatic ring.66-70 For example, the two thiophene derivatives in Scheme 2 give rise to two isomeric l,2-dithiole-3-thiones.71... 

In the first a disubstituted aromatic compound is synthesised first. The second ring is then built on this by standard methods. 

---