Conformational analysis of cyclohexane

F. G. Morin and D. M. Grant, Conformational Analysis of Cyclohexanes, Cyclohexadienes and Related Hydroaromatic Compounds, P. W. Rabideau, ed., VCH, Weinheim, 1989. 

Conformational analysis of cyclohexane derivatives containing several different substituents follows along the same lines as that of the dimethylcyclohexanes. We need to keep in mind that, of two groups, the larger one will tend to call the tune. Because of its very large 1,3-diaxial interactions (Problem 9.3, p. 301), the bulky /er/-butyl group is particularly prone to occupy an equatorial position. If—as is usually the case—other substituents are considerably smaller than tert-butyl, the molecule is virtually locked in a single conformation the one with an... 

Figure 12.68 The conformational dependence of vicinal coupling constants and conformational analysis of cyclohexanes and heterocyclohexanes.

An energy diagram showing the conformational analysis of cyclohexane. 

In Summary The conformational analysis of cyclohexane enables us to predict the relative stability of its various conformers and even to approximate the energy differences between two chair conformations. Bulky substituents, particularly a 1,1-dimethylethyl group, tend to shift the chair-chair equilibrium toward the side in which the large substituent is equatorial. 

Polycyclic compounds are common in nature, and many valuable substances have fused-ring structures. For example, steroids, such as the male hormone testosterone, have 3 six-membered rings and 1 five-membered ring fused together. Although steroids look complicated compared with cyclohexane or decalin, the same principles that apply to the conformational analysis of simple cyclohexane lings apply equally well (and often better) to steroids. 

The principles involved in the conformational analysis of six-membered rings containing one or two trigonal atoms, for example, cyclohexanone and cyclohexene are similar. The barrier to interconversion in cyclohexane has been calculated to be 8.4-12.1 kcal mol . Cyclohexanone derivatives also assume a chair conformation. Substituents at C2 can assume an axial or equatorial position depending on steric and electronic influences. The proportion of the conformation with an axial X group is shown in Table 4.4 for a variety of substituents (X) in 2-substituted cyclohexanones. 

As is well known, the conformational properties of cyclohexane form one of the classical problems of conformational analysis (104) and have been the subject of numerous earlier computational studies (11, 41, 82,105-107). Cyclohexane shows a variety of very interesting conformational properties which make it an ideal candidate for illustrating key features of conformational calculations. 

Cyclohexaamylose-N-methylacetohydroxamic acid, preparation of, 23 254 Cyclohexadienes, 20 293 reaction with HCN, 33 19, 20 on silica, reactions of, 34 54-56-34 64 cracking, 34 55, 72 vibrational spectra, 42 243 Cyclohexadienyl radicals, ESR of, 22 300 1,4-Cyclohexanediols, conversion of ethers, mechanism, 35 361-364 Cyclohexanes, 33 101, 102, 103 autoxidauon of, 25 303 conformational analysis of, 18 9-17 dehydrogenation, 31 14, 21-22 benzene accumulation over platinum, 36 18... 

Spherical polar coordinates are used for conformational representation of pyranose rings in the C-P system. Unlike the free pseudorotation of cyclopentane, the stable conformations of cyclohexane conformers are in deeper energy wells. Even simong the (less stable) equatorial (6 = 90 ) forms, pseudorotation is somewhat hindered. Substitutions of heteroatoms in the ring and additions of hydroxylic or other exocyclic substituents further stabilize or destabilize other conformers compared to cyclohexane. A conformational analysis of an iduronate ring has been reported based on variation of < ) and 0 (28), and a study of the glucopyranose ring... 

In 1937 Isbell published an important paper on the conformational analysis of aldopyranoses, in which several of the forms were depicted (see Fig. 2). They comprise a 4C, chair (I), afl03 boat (II), two half-chairs (III and IV), and a coplanar pyranose (V). He correctly favored the chair form (I) and predicted that, in the case of saccharides, the chair would tend to assume a somewhat flatter conformation than that of carbocycles such as cyclohexane because of the smaller bond angles of oxygen as compared to those of carbon (105° instead of 109.5°). We now know that such coplanarity is strongly avoided because of the strain that would be produced and because of the repulsive forces between the substituents. 

Conformational analysis of rings larger than cyclohexane is more complicated. These rings are also less common than cyclohexane, so we discuss their conformations only briefly. As can be seen from Table 6.1, the seven-membered ring compound cycloheptane has only a small amount of strain. Obviously, it is nonplanar to avoid angle strain. It does have some torsional strain, but the overall strain is comparable to that of cyclopentane. It is a fairly common ring system. 

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