Cyclic molecules conformations

Various di- and polysubstituted cyclic compounds provide other examples of molecules having planes of symmetry. Since chirality depends on configuration, not conformation, cyclic molecules can be represented as planar structures to facilitate recognition of symmetry elements. These planar structures clearly convey the cis and trans relationships between substituents. Scheme 2.1 gives some examples of both chiral and achiral dimethylcycloalkanes. Note that in several of the compounds there is both a center and a plane of symmetry. Either element of symmetry ensures that the molecule is achiral. 

An acyclic molecule has more entropy than a similar cyclic molecule because there are more conformations (cf. hexane and cyclohexane). Ring opening therefore means a gain in entropy and ring closing a loss. 

Thiourea canal inclusion compounds 19 26) have a wider diameter than those formed by urea, such that n-alkanes are not included but that molecules of cross-section approximately 5.8-6.8 A are trapped 64). Thus many inclusion compounds have been reported between thiourea and branched alkanes or cyclic molecules. Of special interest are the inclusion compounds with cyclohexane derivatives and the recent studies carried out on the preferred conformation(s) of the ring in the restricted environment of the thiourea canal. 

More evidence for the existence of several conformational isomers, at least in liquid and gaseous substances comes from infrared and also Raman spectra. For example each conformer has its own I.R. spectrum, but the peak positions are often different. Thus the C-F bond in equatorial fluorocyclohexane absorbs at 1062 Cm-1, the axial C-F bonds absorbes at 1129 Cm . So the study of infrared spectrum tells, which conformation a molecule has. Not only this, it also helps to tell what percentage of each conformation is present in a mixture and since there is relationship between configuration and conformation in cyclic compounds the configuration can also be frequently determined. 

The preceding prediction rules are largely restricted to acyclic compounds. But there is also a considerable need for parameter sets enabling the spectroscopist to calculate I3C chemical shifts of conformationally defined cyclic molecules, especially of the cyclohexane type. Methyl-group effects in methylcyclohexanes (100,101) that are to be added to the basic value for cyclohexane itself (8 = 27.3) are listed in Table 29. Analogous methyl-group parameters in tetralins and tetra-hydroanthracenes have been reported (403). 

Table 8-2 Conformational Energy Differences in Cyclic Molecules... 

Conformational energy differences for a small selection of acyclic and cyclic molecules obtained from 6-31G, EDF1/6-31G, B3LYP/ 6-3IG and MP2/6-31G models are provided in Tables 14-2 to 14-5, respectively. Results from exact geometries are compared with those obtained using structures from MMFF, AMI and 6-3IG calculations. 

A mathematical method is developed to provide a solution to two problems hitherto arising in conformational energy calculations of oligomers and polymers, when bond length and bond angles are maintained fixed. The two problems are the calculation of the sets of dihedral angles which lead to (a) exact ring closure in cyclic molecules and Ibl local conformational deformations of linear or cyclic molecules. Most of the emphasis is placed on polypeptide chain molecules. 

Some 20 years ago it was observed that certain antibiotics could induce the movement of aqueous K+ ions into the mitochondria of cells, but not that of aqueous Na+ ions. These antibiotics, many of which are naturally occurring, are termed ionophores, i.e. neutral molecules which can mediate the transport of the essential groups IA and IIA cations across biological membranes.76 The essential features of an ionophore are a highly polar interior, a hydrophobic exterior and conformational flexibility. Many are cyclic peptides, the coordination properties of the cyclic molecules are considerably different to those of the linear peptides. These differences are outlined in Chapter 20.2. 

Problems 1-3 emphasize the three dimensional representation of various cyclic molecules and evaluation of their energies by the A, G, and U parameters. In Problems 4-6, we apply conformational analysis to predict the reactivity of carbocyclic systems toward various reagents and to gather information regarding the preferred stereochemical course of the corresponding reactions. Further examples of applications of conformational analysis in organic synthesis are incorporated in Problems 7-9. 

These two reactions are not nearly as diastereoselective as most of the reactions of cyclic compounds you met in the last chapter. But we do now need to explain why they are diastereoselective at all, given the free rotation possible in an acyclic molecule. The key, as much with acyclic as with cyclic molecules, is conformation. 

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