Cyclohexane monosubstituted derivatives

Conformational inversion (ring flipping) is rapid in cyclohexane and causes all axial bonds to become equatorial and vice versa As a result a monosubstituted derivative of cyclohexane adopts the chair conforma tion in which the substituent is equatorial (see next section) No bonds are made or broken in this process... 

Exceptional fluorescence properties also characterize the ri.s-isomer 38e. Unsubstituted cis-l,2-di-9-anthrylethylene 38a and its monosubstituted derivatives such as 38b are nonfluorescent at room temperature. By contrast, cis-dianthrylethylene 38e does fluoresce with quantum yields of 0.0018, 0.0042, and 0.0064 in cyclohexane, dichloromethane, and acetonitrile, respectively. The emission is structureless (see Figure 18), and is associated with a solvent-independent Stokes shift of about 6000cm-1. As the molecular geometry of 38e is characterized by overlapping anthracene systems [80], the structureless emission may be attributable to an intramolecular excimer state. 

The H NMR spectra of quinoxaline and its monosubstituted derivatives have been reported <67JCS(B)l24l>, and those of di- and trisubstituted quinoxalines have also been measured <68JCS(C)1274>. The spectra of a number of phenazine derivatives have been reported <66CPB419>. The H NMR solvent shifts in acetone, carbon tetrachloride and cyclohexane have been measured for the parent pyrazine, quinoxaline and phenazine <86BCJ1650>. For the last two compounds the NMR spectra of both for the neutral and the acidic species are reported <91BCJ2668>. 

The consequences of this point aie developed for a number of monosubstituted cyclohexane derivatives in the following section, beginning with methylcyclohexane. 

Fig. 2-10. Ring inversion of a monosubstituted cyclohexane derivative equatorial substituents become axial and vice versa.

Standard free energy change for the axial-equatorial equilibrium in monosubstituted cyclohexane derivatives (from [103])... 

As Table 1.1 shows, fluorine is the second smallest element, with size approximately 20% larger than the smallest element, hydrogen. Table 1.2 summarizes four steric parameters for various elements and groups (i) Taft steric parameters Es [44], (ii) revised Taft steric parameters E [45], (iii) Charton steric parameters o [46], and (iv) A values [47], The steric parameters, Es, E, and u are determined on the basis of relative acid-catalyzed esterification rates, while the A values are derived from the Gibbs free energy difference calculated from the ratios of axial and equatorial conformers of monosubstituted cyclohexanes by NMR. 

For a monosubstituted oxane, the excess free enthalpy of the conformation with an axial substituent over the conformation with an equatorial substituent is, as we know by definition, the conformational free energy (CFE) of the substituent in oxane at this position. These values, possibly measured indirectly by utilizing intennediate compounds, are shown in Table 2.2. Equatorial conformations correspond to anti conformations in butane and methoxyethane, and the axial conformations (not represented) to gauche conformations. We can observe that the environment of derivative 2.20 is closest to that of the cyclohexane and that the CFE is of the same order. On the other hand, the presence of the cyclic oxygen lowers notably the CFE of derivative 2.19. The important point is the noteworthy increase in the CFE of compound 2.18, where the methyl group is close to the cyclic oxygen and possesses, on one side, an environment similar to that of methoxyethane. Let us look at the equilibrium (2.4) of the dimethylated derivative 2.21. 

Reaction of DBD with 1-A-morpholino- or 1-iV-piperidinocyclohexene gives the 1,3,4-oxadiazine (170), hydrolysis of which gives the monosubstitution product (171) or cyclohexane-1,2-dione (172) (Scheme 179). The analogous adduct to 170 from the pyrrolidine enamine could only be isolated by working with an excess of the enamine. Otherwise, further reaction occurred to give the products of 2,6-disubstitution (173 and 174) on hydrolysis however, the main product was the oxadiazine (175) derived by 2,2-disubstitution and isolated in 50-80% yield Such is the reactivity of DBD that simply heating with cyclohexanone gives 171 . With 2-methylcyclohexanone enamines the normal product 176 of 2,6-disubstitution is, however, formed (Scheme 180). 

Figure I. Conformational interconversion of monosubstituted cyclohexane derivatives 1 (twist-boat intermediates disregarded).

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