Cyclohexane derivatives, conformational analysis

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. 

The fluorescence In dilute solution is measured for five polyesters with terephthalate as the rigid aromatic unit and diols derived from cyclohexane as the flexible spacer, A conformational analysis concludes that the spacers most conducive to excimer formation are the 1,3-c/s-cyclohexanediol and 1,4-e/s-eyclohexanedimethanol. This result from calculations is compatible with experimental results. 

H-NMR studies on 2,6-dimethylmorpholine314 and N-substituted 2,6-dimethylmorpholines315 are consistent with the single diequatorial conformation 391 for the cis isomers and with the equilibrium 392 393 for the trans isomers. The 13C-NMR spectrum of the monomethyl-, 2,3-, 2,5-, 2-6-, 3-5-dimethyl-, 2,3,4-, 2,3,6-trimethyl-, and 2,3,5,6-tetramethylmorpholines are largely consonant with expectations based on conformational principles derived from cyclohexane conformational analysis.316 The all-cis 2,3,5,6-isomer, which did not prove amenable to analysis by H-NMR spectro-... 

The studies of cyclohexane and its derivatives by Hassel and co-workers in the late thirties and early forties using mainly the electron diffraction method laid the foundation of conformational analysis. In 1943 Hassel295 summarized that cyclohexane exists mainly in the chair conformation as distinct from any other possible conformation. The chair conformation will have distinguishable axial, a, and equatorial, e, substituents. (See Fig. 13). The equatorial position is the energetically favored one. Furthermore, Hassel stated that there is a rapid inversion of the ring with an associated low barrier. This motion interchanges the a and e positions with the result that a and e conformers cannot be isolated. 

Use analysis of conformations to determine the relative stabilities of stereoisomeric cyclohexane derivatives. (Problems 6.23, 6.24, and 6.26)... 

Let us apply the methods of conformational analysis to the stereochemistry of cyclohexane derivatives and, since we are already somewhat familiar with interactions of the methyl group let us use the dimethylcyclohexanes as our examples. 

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... 

Corey and Feiner have developed a computer program (LHASA) for conformational analysis and for determining the destabilization energies (Ep) in substituted cyclohexane derivatives. In the following discussion, we will adopt their A, G and U designations and use the corresponding values for evaluating steric interactions. 

Conformational analysis is defined in a recent book by Eliel et al. (30) as an analysis of the physical and chemical properties of a compound in terms of the conformation (or conformations) of the pertinent ground states, and (in the case of spectra) excited states. For additional background see Stereochemistry of Carbon Compounds by Eliel (31), Steric Effects in Organic Chemistry by Newman (32), and The Stereochemistry of Cyclohexane Derivatives by Orloff (33). 

Discussion of the physicochemical sizes of substituents on the basis of conformational analysis of the torsional process of substituted cyclohexanes, cyclophanes, and diaryl derivatives have been summarized by Schlosser [5]. The energies required for the conformational exchange of an equatorial position to the axial position for each substituent in cyclohexane are listed in Table 1.47 [6]. For fluorine, the energy difference between the axial and equatorial environment is negligibly small as compared with methyl, while that of CF3 seems larger than that of z-Pr so far observed in the cyclohexane torsional system. From the... 

Use analysis of conformations to determine the relative stabilities of stereoisomeric cyclohexane derivatives. 

A conformational analysis of the cyclohexane, oxane, and thiane derivatives bearing both trimethylsiloxy (or methoxymethyleneoxy) and tributystannyl groups at the geminal position has been performed by Goto et a/. on the basis of Vcsn couplings and C NMR chemical shifts measured at low temperature. 

Van t Hoff appreciated that free rotation occurs about single bonds. The consequent different arrangements of atoms in space were termed the conformations of the compound by Walter Norman Haworth (1883-1950) in 1929. In 1936 K. S. Pitzer pointed out that there would be an energy barrier to rotation about the carbon-carbon bond in ethane caused by repulsion between the hydrogen atoms, but it was studies on cyclohexane and its derivatives which emphasised the importance of conformational analysis. 

In the 1930s, Odd Hassel (1897-1981) studied the geometry of cyclohexane derivatives by means of X-ray and electron diffraction studies. X-ray diffraction confirmed the existence of the chair form, and electron diffraction revealed that liquid cyclohexane was oscillating rapidly between the possible forms. In 1950 Derek H. R. Barton (ft. 1918) stated the basic principles of conformational analysis as applied to cyclohexane derivatives. He pointed out that molecules with... 

Hassel, Odd (1897-1981) Norw ian chemist who used X-ray and electron diffraction methods to determine the molecular structure of the petroleum-derived solvent cyclohexane and related compounds. Cyclohexane is not a flat molecule and can adopt a boat-shaped or a chain conformation. Hassel s work brought to the fore the importance of conformational analysis. He shared the 1969 Nobel Prize in chemistry with Derek Barton. 

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