The Effect of Heteroatoms on Conformational Equilibria

As the ring size increases, the number of possible conformations increases further so that many alternative diamond-lattice conformations are available.  

The replacement of carbon by other elements produces changes in several structural parameters and consequently affects the conformational characteristics of the molecule. In this section, we will first describe some stereochemical features of heterocyclic analogs of cycloalkanes. For the purpose of elaborating conformational principles, the discussion will focus on six-membered rings, so that the properties may be considered in the context of a ring system possessing a limited number of low-energy conformations. 

It is consistently found that 5-alkyl substituents in l,3-diqxane exhibit a smaller equatorial preference than they do in cyclohexane. This decreased preference is due to 

Group Cyclohexane 2-Position 2-Position 5-Position 2-Position 5-Position 

An important feature associated with heterocyclic rings is the reduction in steric repulsions for axial substituents that results from replacement of a methylene group in cyclohexane by oxygen, nitrogen, or sulfur. This effect is readily apparent in d5-2-methyl-5-r-butyl-l,3-dioxane, in which the preferred conformation has the r-butyl group axial and the methyl group equatorial. Divalent oxygen has no exocyclic substituents so the 1,3-diaxial interaction, which is the main unfavorable interaction for axial substituents in cyclohexanes, is not present. 

The decreased preference for the equatorial orientation of a 5-alkyl group in 

3- dioxanes and 1,3-dithianes is evident from these data. It is also interesting that the increased preference for the equatorial orientation of a 2-methyl group in 

3- dioxane disappears in going to 1,3-dithiane. The conformational free energies of 2-alkyl substituents in 1,3-dithiane are very similar to those in cyclohexane (actually, slightly smaller) because of the longer length of the C—S bond compared to C—O. 

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